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All Lectures Transcripts 1.1 Cancer - Introduction and Epidemiology 1.2 Cancer Nutrition & Lifestyle Strategies for Cancer Prevention and Risk Reduction 1.3 Cancer Screening and Hereditary Syndromes Overview 1.4 Comprehensive Overview of Cancer Theories & Hallmarks Of Cancer 1.5 Monthly Q&A 2.1 Overview Of Cancer Treatment 2.2 Troubleshooting Common Problems During Cancer Treatment 2.3 Cancer and Menopause Management Insights 2.4 Comprehensive Cancer Rehabilitation and Support 2.5 Radiotherapy and Hormone Therapy Insights 2.6 Managing Interactions in Integrative Cancer Care 2.7 Targeted Therapies and Immunotherapy in Cancer 2.9 Live Meeting Month 2 3.1 Introduction to Systems Approach to Cancer 3.3 Mental/emotional/spiritual health & biorhythms 3.4 Microbiomes, GI function and cancer 3.5 Immune Function in Cancer 3.6 Effective and balanced detoxification 3.7 Month 3 Live Meeting 4.1 Circulation and tissue architecture (invasion, angiogenesis and metastasis) 4.2 Understanding Hormonal Influence on Cancer 4.3 Metabolic and mitochondrial health 4.4 Cancer metabolism and special diets (part of Metabolic and mitochondrial health lesson) 4.5 Methylation and Cancer Genomic Stability 4.6 Bonus material from the Hormone GATeway course 1.1 Cancer - Introduction and Epidemiology Today we'll be talking about cancer just giving a general introduction to the topic and talking about epidemiology so just a general disclaimer um a little bit about my affiliations which you hopefully all know about so what is cancer well cancer is really a group of diseases not a single disease um it's a group that is characterized by abnormal cells dividing without control and invading nearby tissues as well as spreading to other places in the body and that's called metastasis and there are different types of cancer that are named for the tissues of origin so the way that a cancer is named tells you something about which area of the body the cancer has come from so a carcinoma is a cancer that begins in the skin or the tissues that line or cover internal organs are called epithelial tissues so something called an arinac carcinoma is a cancer of the gland epithelium Esa cell carcinoma is a cancer of Thea cell epithelium esom is a cancer that begins in the connective or supportive tissue so things like bone cartilage fat muscle or blood vessels and they also have some different um additional names so for example angio saroma angio stands for blood vessel effectively and saloma means of course a connective tissue cancer so angio Scoma is a cancer effectively of the blood vessels um so it's an important one to understand the nomenclature because it can help us um get a really good idea about where the cancer is coming from and Its Behavior as well leukemias and lymphomas are things that are blood cancer so leukemia is a cancer that begins in blood forming tissue such as a bone marrow and often causes too many abnormal blood cells to be made and there are different types of leukemias of course and Lymphoma multiple Myoma cancers are in the cells of the immune system um and so lymphomas for example will quite often present in um areas that have a concentration of these cells for example lymph nodes central nervous system cancers are Cancers begin in the particular tissues of the brain and spinal cord and these are just some examples to get you started as you can see there's a huge amount of tumor nomenclature and there's different uh names being given to benign tumors so these are tumors that don't actually go off and invas surrounding tissues per se or metastasized to other different sites but they can still cause symptoms by compression just by growing effectively and then malignant um tumors are the cancer effectively and that's the ones that we are interested in and as you can see they have some overlap in the way that we call something so for example ayoma is a benign tumor of the smooth muscle so in the uterus that would be a fibroid but when we when that tumor becomes Mal ignant we would call it a liom saroma and that's a malignant tumor of the smooth muscle for example again you don't need to know all of these but I think it is important just to have an idea that the way the cancer is described and it's can actually tell you what tissue comes from and a little bit of something about Its Behavior as well so what is the problem with all of this really so the key thing that I need us to think about is that one in two people in the UK will develop some form of cancer during their lifetime uh and that's a huge problem so you can see 2014 um the estimated population 65 million okay then 73 million by 2035 and you can see in terms of cancer due population change more aging population there's going to be an additional 14,600 cases as well as the risk factor change is contributing more so the total cases in 2035 per year exceeds 500,000 which is huge okay this is 2014 the total of 360,000 or so so this is a huge growing chronic disease epidemic that we need to manage and we're also now having better survival which is fantastic but that does mean that we're now having a hugely growing population of cancer survivors that quite oftenly not managed properly so the most common cancers uh more than half of new cases of cancer breast prostate lung or bowel cancer for example so as you can see in the males uh prostate would be the most common then lung then bowel and in the females breast then lung then bowel and so I want to talk a little bit about statistics and epidemiology and really we want to be talking about incidence and prevalence so it's important to Define these terms so you know what we're talking about so incidence of disease number of new cases during a specified time period so quite often we will talk about per year for example a prevalence is a very different thing so prevalence is a number of the individuals with the disease either at a specific time point so for example right now or over a specific time period so it's not new diagnosis it's a number of individuals with the disease and the prevalence of disease in the population will be influenced by a number of different things so how many new cases are coming in how many people are recovering for example and how many people die and lose their lives to the disease and so most of the statistics we'll be talking about here will be more about incidents so in terms of UK cancer incidents it has rained higher than 2/3 of Europe and ranked higher than 90% of the world so we can see we've got a huge problem in our hands they're around 375,000 400 new cancer cases in the UK every year which is a huge burden and every 2 minutes in the UK someone in the UK is diagnosed with cancer and you can see the survival is improving nearly 50% of um those diagnosed with cancer Will Survive a 10 or more years but you also have a huge amount of potentially preventable cases so 38% I think that number is actually probably lower than we it potentially could be if we consider the gene environment directions properly but you can see there's a huge amount of burden of disease but also preventable disease around as well okay so now let's talk a little bit about the cancer incidents in the UK in terms of the trends so the incidence rate that's the number of new cases has been increasing since the early 1990s and that has increased by more than 10 so 12% in the UK in both females and males and there's a significant issue with almost half 45.5% of all cancer cases being diagnosed at Advanced stage and that's stage three and stage 4 um and that's a significant problem because of course the options there and the survival there are going to be very different than in early stage one stage two cancers and socioeconomic status and deprivation plays a huge role so significant amount of Health inequalities within cancer do really need to be addressed so for example all cancer combined if we look at the incidence rate so that's new cases in England in females are 16% higher in the most deprived quinal of the population versus the least and in males the the dispari is even bigger at 19% it's estimated that around about just under 177,000 of all cancers every year in England are linked with deprivation so it's a significant issue the other things that I want to highlight here really is the fact that um the cancer um the cancer patterns are changing as well so we know that there's a top four and they're going to stay top four really that we we know about those that's absolutely fine and I'll talk you through the top 20 most common but there's also some changes in the different cancers as well we're seeing some um cancers are rising so things like thyroid cancers are on the rise and there are some cancers that are actually decreasing over time and there's a paper there for you to look at from the British Journal of cancer if you want to know a little bit more but the 20 most common Cas cancers in the UK are all listed here so as you can see breast prostate lung and bowel are the top the melanoma non hodkin lymphoma and then we've got the other cancers uh further down the line uh and Cancers of unknown primary uh the cancers that we don't know where it comes from we found a metastatic deposit somewhere but we're not sure where they originating cancer is so in terms of the different Trends I mentioned the cancer um distribution is changing somewhat over time so this is comparing um over the last 10 years really between 2006 2008 and 2016 and 18 and was decreasing and uh increasing and as you can see in terms of decreasing cancer of unknown primary is decreasing well that's just because we've gotten really much better at identifying the tissue of origin where did that cancer come from uh stomach cancer is decreasing which will be due to the fact that we are a lot better eradicating things like kakop palori for example um so AIA cancer is decreased somewhat and that might be for different reasons including more surveillance in terms of bar esophagus and some of the interventions there but you can see a significant amount of increase and I've mentioned thyroid cancer just a few moments ago and that's there's a significant rise in thyroid cancer over time and and people have been arguing about it is it over diagnosis and probably there is a component of overdiagnosis but there's also a component of the fact that the thyroid gland is a little bit like a canaran a Coal Mine It monitors a lot of the environmental uh exposures uh and therefore that's a significant issue we also got to consider that there are some um conditions particularly autoimmune thyroid disease can also be linked to some specific types of thyroid cancer potentially and that's also been increasing so there may potentially be some overdiagnosis but there's also a real rise which may or may not be due to um the overall pattern between environmental exposures maybe some of the autoimmune thyroid disease maybe something else that we don't even know about and you can see melanom and kidney cancers are on the rise as well and liver cancer and that's unsurprisingly related number of things that will be related to things like the rising metabolic syndrome um so that's the non-alcoholic fat liver disease for example can progress to various things but also of course alcoholic liver disease will increase the risk of liver cancer as well as some of the viral exposure such as hepatitis viruses in terms of the males um you can again see a relatively similar Trend here uh but you can see so melanomas on the right is still kidney cancer on the rise thyroid cancer still on the rise and liver cancer so it's a relatively um similar pattern although they have a few more Rising things like hodkin lymphoma Etc so now I'm going to go into the foro common cancer and then pick up a couple of the others just to illustrate a few points so breast cancer we can see there's around about 56,000 of new cases of breast cancer per year and the great news is is now 76% uh of women who diagnosed survived breast cancer for 10 or more years and it's estimated that 23% or nearly a quarter are preventable and again I feel like that number is probably a little bit on the low side if we really look at the gene environment interactions properly um the statistic is now that 1 in seven UK females will be diagnosed with breast cancer in their lifetime it used to be 1 in8 and the first symptom of breast cancer the most women might notic uh is the lump in their breast or some thickening and so it's really important to look out for any changes in the breast and that's when we're talking about Touch look and make sure you do it regularly and make sure that women understand what's normal for them at different times of their cycle so any lumps thickenings changes in the size shape of feel of the breast skin changes any fluid discharge or changes in nipple position really need to be taken uh to the GP straight away so how we detect breast cancer there's there's more things that we're going to be talking about terms of detection but self- examination is really important all women you all girls or all people who have breasts should be encouraged to self-examine by any professional they come across so Copperfield has a really great video guide um in terms of what to how to get to know you and they also can send you a monthly message to check your breast which is great so anytime you see anybody who has breast really need to make sure that they understand how to check them so send them to the website as early as possible really girls should start checking their breast and their teens and know what's normal for them and how things are changing so mamography screening um it's really important to note that that's still a stand of care in the UK we can argue about the fact that it does cause some harm as well as potential over diagnosis but it is still the screening method and theography is a breast health tool it's currently not validated as a breast cancer detection or monitary modality it might change in the future but it really isn't part of the care now and it's important to understand why if it was less exposure to radiation plus it was a validate tool it would be actually being done now but it's not so mamography ultrasound MRI are usually used as appropriate to the particular case in the different clinics and these days if you have a lump you will go into effective triple assessment Clinic you'd get EX examination you'd usually get a mamography and an ultrasound and a biopsy if and there anything to biopsy um and it you usually get uh results very very quickly out of that so that's the two week weight referr to this kind of One-Stop Clinic um and so as we know self-examination should be done all the time mamography screening is done specific age group so it's targeted really at um well we're now seeing women about 47 upwards in some regions but really in their 50s and we tend to stop at a certain point much later in life um and the if you do have a lump or anything to check out you'd usually be referred as an urgent referral into One-Stop clinic so there's definitely places where we can contribute as nutritional therapists it's really really important 8% of breast cancers in the UK are caused by obesity and weight management is definitely something that we can absolutely support people with and 8% caused by excessive alcohol GS and there is no self level of alcohol unfortunately in breast cancer so so we've got a major major contribution to make here you know 16% we could potentially knock off the new cancer case if we manage those risk factors well and 1% is caused by ionizing radiation could be different radiation exposures now this is a busy table I don't need you to know about it very much but these are the specific risk factors that have been highlighted by the International Association um for the research in terms of cancer risk factors and the world cancer research fund and they effectively will put risk factors into sufficient or convincing evidence and limited or probable evidence so you can see the different parts of um the definitely increas in risk and sort of potential increase in risk and there's some also decrease in Risk so for example physical activity breastfeeding Etc so the key modifiable risk factors that we've explained before would be things like weight alcohol contra receptive fi exposure HRT might play a role and of course being inactive being physically inactive not reaching excess targets but also being sedentary so HRT and we're going to need to consider the full context here um and so what we've got here for example is if there are 23 cases of breast cancer diagnosed UK general population per thousand women in their 50s if you use combined HRT and that's just a standard type of HRT not body identical not bioid didn't just a normal HRT you'd get four additional cases per thousand okay interesting enough it appears that women who have had their WBS removed and they can have estrogen only HRT they might get some fewer cases so there's some arguments about that so You' also get the same risk with combined oral contraceptive pill but look at the alcohol two or more units of alcohol a day and that's really a large glass of wine would give you two or more alcohol units a day and that five so that's more than what we're looking at with HRT interesting enough the three in covered smok is per thousand and a huge increase in women who are overweight and obese and a significant reduction in women who take moderate exercise so just in terms of context as we know that HRT reduces symptoms of menopause it can make a significant difference to a woman's quality of life and it potentially can slightly reduce the risk of things like bow cancer and the other diseases however if a thousand women started taking HRT at age 50 and they only took it for 5 years again risks go up the longer you take HRT two more women would get breast cancer per thousand and one more woman would get aarian cancer per thousand can also affect endometrial cancer or wound cancer risk but that depends on different factors now what's really interesting though is just look at how much you compare to the lifestyle factors so if we completely avoid HRT we might prevent under 2,000 cancer cases per year but keeping a healthy weight we could prevent 18,000 cancer cases and being smoke free we can prevent over 60,000 cancer cases so just remember the fact that HRT for women who is not the devil either okay it can be really supportive for some women who are really really struggling with the menopausal symptoms um and it should not be completely avoided by people but it's also not the Panacea that some of the people out there claim it to be and everybody should be in HRT no matter what because it does still have risks so do remember that as's a medical treatment discussions around risk and benefit of HRT for the individual client in front of you is out of scope for nutritional therapist they should always be discussed with the doctor no matter what your opinion on that is it is your client's individual medical decision to be made with their doctor so just in terms of a balance you and again I just kind of giving you an overview it's not something for you to discuss with your clients but it is really important that they do get a Balan do discussion risk and benefits and it may be that we want to be preferring things like body identical HRT with a topical estrogen which will reduce the risk of clots compared to oral estrogen and oral progesterone is a typical thing so you can get a topical estrogen through things like estrel or a patch or a linetta spray for example all sorts of things like that and or progesterone utrogestan that's available on the NHS or we can get biodental HRT that needs to be appropriate so not high dose it needs to be well balanced needs to be properly monitored and that might be preferred over synthetic progest oral estrogen which can increase risk of clots and complications for people so that would be my opinion on it but there's also really important to realize that there is a lot of overstating there that biodental HRT is risk neutral it doesn't increase the risk of breast cancer we haven't proven that in long-term studies so it's really important to say that there there may be less risk but we don't know to what extent and we don't actually have any proof over 10 20 years that they're they're risk neutral so it's important to see the studies that are going to be coming out over the next say 10 15 years Etc but for the moment we don't have uh any evidence it's risk neutral whatever other people are saying out there and it's really important to have a really good detector for when people are overstating over claiming things saying what's the evidence like can I find any evidence support it can I ask that person where is their study for you know 100,000 plus women over 20 years it shows that it doesn't in Risk at all it's important to know that HRT use uh also interacts with lifestyle in the clinical background so for example if you have metabolic syndrome which is a typical cluster of metabolic conditions and you can look it up here uh and you use HR as well it does significantly increase risk of your postmenopausal breast cancer so hit increases a little bit metabolic syndrome composition body composition for example obesity will be a part of metabolic syndrome will increase it significantly and together they will combine and make it even worse so that's an important consideration for women as well and there may be some role for the snip background so it may be that on average H doesn't risk for very much but actually for that one single person because they've got some significant um combination of snaps a number of different snaps that might confer only a small amount of risk individually but all stack up over time and then you give them HRT as an exposure it might be that for that individual the risk is significantly worse and that's really what the study suggests and I wouldn't get hung up on any specific snip because there's never one thing but we know that M and sod Snips for example for um can um increase risk of breast cancer with long-term HRT use cp1 B1 and what was really interesting was there was a finished study that that showed that a combination of the compt L alel genotypes plus a gstm1 null so deletion in gstm1 gene poses significantly increased risk that's ninefold increased risk of breast cancer with HRT Us in postmenopausal women so is definitely something to think about although we would need to think about how we read screen for it and it's certainly not a discussion that you would have because you're not really a medic and you're not going to be able to counsel women around HRT risks and benefits fully so in terms of other risk factors these are considered non modifiable though I'd argue with that I'd argue with the fact that you could actually modify things like set your diabetes risk um and other things like that so but effectively age family history various inherited um conditions uh we talked about ionizing radiation of course metabolic syndrome diabetes dense breast issues for women with denser breast are more likely um to have a high increase risk of um breast cancer so and also harder to monitor because mammograms can miss small breast cancer is a very dense breast tissue some benign breast diseases can also cause an increase rest dcis or lcis are the precancerous conditions in the breast so they're called carcinoma in situ and there's also the estrogen window so the age when period starting stop the longer the early you start and the the kind of later you stop effectively the uh exposure to the hormones that window is longer and therefore the risk is higher of course exposure to various hormones things like contraceptives and HRT ethnicity plays a role so there is definitely um an ethnic breakdown um and we also know in women of color they're more likely to present with more aggressive uh Cancers and also later so there is certainly a health in equality there as well previous history of cancer height interesting enough and not having children having them later in life so prostate cancer now we're moving on from breast to the most common cancer in male so prostate cancer over 50,000 cases per year again very survivable um very similar to breast cancer look at 76% this is 78% for 10 uh years plus interesting enough it say not clearly linked to any preventable risk factors I have to say I think this because it's a quite a heterogeneous so variable group of um variable disease really but in my clinical practice I do see a significant association with metabolic compromise personally and there is some evidence around that so prostate cancer may not cause any symptoms most prostate cancer tend to start in the outer part of the prostate gland which means it needs to be really really big by the time you get urinary symptoms such as dribbling and getting up at night difficulty passing urine and the the thing is actually as men get older quite often they will get what we call benign prostatic hypertrophy which is just an increase in the size of the prostate gland and that will give you a number of these symptoms so can be absolutely unrelated to any kind of prostate cancer it's just the prostate gland getting bigger and effectively compressing the urethra a bit more but there are some symptoms you can look at here but I would say that um it's important to know that sometimes proy cancer doesn't really present until quite late um in people without necessarily having urinary symptoms beforehand lung cancer now this is quite a contrast so look at the survival rates here okay so just under 50,000 cases per year 10% only survive at for 10 or more years after donos of Lanka so it's it's a really really huge problem but look at the amount that's preventable nearly 80% so again a huge role here for both Public Health but also for us as Healthcare professionals to be able to intervene and support people so let's have a look at that and in terms of most common symptoms of L cancer you probably would have seen them before so cough for example have having yet most of the time persistent cough a new change in cough if you had a chronic cough so a lot of smokers will have a chronic cough but they might change character shortness of breath coughing up anything with blood so blood is always as you know a red flag for anything has to be referred straight away um chest infections that are recurrent and persistent and things like um chest pain losing appetite feeling tired all the time and weight loss and lung cancer does have a significant amount of um weight loss as a component to it so I think it's really important to watch for smokers who are suddenly starting to lose weight and becoming fatigued so 72% are caused by smoking so again any time we meet a smoker just supporting the smoking sensation is so so important for in terms of Public Health and reducing their risk of cancer as well as other diseases are caused by smoking caused by occupation to workplace exposures are really important any kind of inhalent um problems from the occupation exposures of course also includes things like air pollution so 8% of case in the UK are caused by air pollution so a number of different things you can see here for um number of different inhaling things number of different um exposures so if you get a person with lung cancer it's really important to take a really good occupational history for those guys in terms of not just smoking but also any other radiation any kind of painting welding uh occupational things they could be exposed to um as well as things like high do bitter car supplementation because has been shown to increase risk as well so let's go back and have a look at choral cancers that's our fourth of the top four um just under 50,000 so around 43,000 of cases per year 53% so not quite as survivable in general as breast and prostate but also not as bad as lung at 10% so 53% survive for 10 or more years and 54% are preventable so again a huge huge role for us to play here with anybody we see really because prevention is everybody's job so coloral cancer bowel cancer symptoms could include all the obvious stuff such as of course bleeding from the rectum more blood in stools change in normal bowel habit so anybody really who has a significant change in bowel habit we needs to be investigated first from the medical perspective before we conclude this all IBS um and actually there's now a significant rise in younger and younger people getting colorl cancer because of such poor dietary quality so it's really really important that we don't don't get dismissed and get told that no you're too young to have coloral cancer nobody's too young and I think we we know through the recent work that's been done uh by a number of public figures that is really really important um nobody is ever too young to get cancer of any kind they need to be investigated so of course weight loss we talked about persistent pain and shortness of breath for example and fatigue due to anemia so sometimes Cola cancer can grow to an EXT way can block the bowel and people can present acutely with bowel obstruction usually they would have been suffering from symptoms for quite some time but they just didn't go to the doctor with those and the symptoms can include really cramping pain feeling very bloated constipation being unable to pass wind anytime someone has what we call absolute constipation not just passing stalls um having problems with that but also being unable to pass when they need to go to an immediately and of course nause if you can't pass from the bottom end of course you're going to be sick from the top end as well so this is an emergency and then it requires any attendance we usually require urgency surgical Ur urgent surgical intervention and quite often people will end up with a sto in the meantime so in terms of coloral cancer risk factors 28% are caused by to little fiber and again this is something that we can all do with everybody we see is making sure they've got their 30 G Plus of fiber daily okay it's really really important um meat it's estimated 13% are caused by eating meat a particular processed meat um and 11% bi obesity again these three things imagine look at the total of this that we could have an impact on if we did some counseling with everybody we see around those risk factors in terms of avoiding process meat making sure we've got enough fiber and managing weight so there's other uh coloral cancer risk factors you'll see all the typicals you know alcohol increasing age smoking family history it's important to know that our IBD patients so inflammatory bowel disease patients uh with UC and Crohn's I increased risk of chacal cancer need to be monitored there are some other um medical condition that will increase the risk as well and radiation assist infections as well so other cancers in brief so melanoma is the fifth most common cancer in the UK um and you can see that of course it's caused by overexposure to ultraviolet radiation in the vast majority of cases that's 86% so making sure we advise everybody we see on sensible sun exposure you know covering up during the vulnerable periods of the day in terms of you know 12 to 3 or 11 to3 whatever guidance you want to use um making sure that people put clean mineral sunscreen on when they're going to be in the Sun for a significant amount of time so melanoma symptoms any changes to mold freckles or normal patches of skin ABCD is a typical thing that you can look up there's some good visual posters online as well that you can look see but ultimately if end downed always check it out so first usually seen by GP and then a consultant dermatologist non hodkin lymphoma as we talk about that's a hematological cancer a it's a effectively blood cancer it's cancer of the the um specific cells in the immune system so it's the sixth most common cancer in the UK uh and there's not as many preventable factors here and about 55% survive for 10 plus years and the most common symptom again sometimes people might complain to you is one or more painless swollen lymph noes in neck armpit groin or anywhere frankly if they persistent and they've been swollen for some time they need to be checked out by the medics and there are some general symptoms b symptoms is what we call those uh that usually are a poor prognostic indicators that's night sweats Fe F that come and go with an obvious cause Lo losing a lot of weight and that's more than one/ tenth of your total weight quickly and unexplained itching which of course can have a number of different causes but if you get a combination of these symptoms and again a very very urgent medical referral is super important the Varian cancer the reason I brought this up is not part of the top six for example but we will quite often get uh people who are presenting with some of these non-specific abdominal symptoms and they think it might be related to food Etc so it's important to know that anybody with some of these vague abdominal symptoms who needs to be checked out who has still has ovaries do need to be checked out for ovarian cancer as well if this is a persistent problem so um because it's it's a really often diagnosed at quite an advanced stage and only has 35% 10 plus survive uh 10 years plus survival and 7% of their caused by obesity again we have a role to play here so in terms of uh ovarian cancer risk factors you can see age inherited mutations play a role previous choral cancer to young age or breast cancer that's also important to monitor for ovarian cancer with those obesity as we mentioned endometriosis diabetes can increase risk HRT smoking environmental exposure such as asbest and radiation so that's what I mean about vague abdominal symptoms really quite often people present to us think oh it's IBS or and it may be IBS but it might not be and it's really important that we have a really low threshold for saying have you been investigated for anything else has your GP cleared you there's nothing else going on medically so because you know thinking about how many people do we see who might feel full quickly who might have some persistent abdominal discomfort who might have bloating who might be needing to go for a Wei more often particularly in the peram menopausal or postmenopausal stage so it's really really important that if there's any changes about habit if there's Nuance at IBS particularly if it's you know after 45 or 50 that is significantly investigated by the GP with all the appropriate modalities and usually that will require some Imaging in a blood test and of course fatigue and weight loss are the typical things as well so brain tumors again they're not part of the top um you know six of the certainly part of the top 20 uh but what I would say is that the reason I'm highlighting those is not only because they're one of the ones that are like lung cancer have a relatively poor long-term survival rate but also because many of our patients might get secondary brain tumors and the the symptoms are actually quite similar whether you have a primary or secondary brain tumor so I just wanted to highlight that so in terms of the most common symptoms of course they will very much very hugely so have a very low threshold and anybody with it history of cancer for just referring the back to see the GP on oncology team headaches morning as usual because you're lying down so where there's a tumor um that's actually compressing normal circulation of the cerebral spiral fluid around the brain there's what we call incre increased intracranial pressure and so usually when you're lying down that's worse so when you wake up you could actually get quite stoning headache or wake up with headache in the middle of the night because you've been lying down and normally would wear off during the day um but that's not always the case sometimes it might have a very different pattern so if anybody who has a history of cancer um no matter how long ago it was it might be 10 20 years ago has a new or persistent headache they must go and see their GP it's really important that anything until water is investigated quite often is the first presentation of metastatic disease recurrence in the brain unfortunately so be very Vigilant obviously you don't going to tell them that but you're going to say okay I just want to make sure there's nothing going wrong with your headache I want to make sure the medical course have investigated why don't you go and see your GP and then come back and see me so nausea again quite often usually with the headache comes an oruse of vomiting or nuan and seizures is quite a dramatic presentation but not that uncommon and other symptoms might depend location within the brain um and so that's important because actually some people get you really weird symptoms like recurrent Deja vus for example or they might have side disturbances but the eye check is absolutely fine but actually there's a tumor in the occipital lobe that's affecting their site because of the visual cortex there might be cerebella tumors people suddenly becoming unbalanced and uncoordinated um there might be temporal lobe uh which are really issues around hearing for example or comprehending language um and frontal lobe is actually personality changes or problems with motor control or problem solving and speaking so there's a number of multitude of ways that that brain tumors whether the primary or secondary present themselves with so just have a low threshold for referrals because the worst that can happen is the GP says it's fine and we've investigated there's nothing wrong it's okay well never mind that's okay but I would rather people get picked up as early as possible if they have any potential recurrence particularly with with the brain because it can get very serious very quickly there are very many cancer types out there I have covered just a really quick introduction so please research and read about some of the cancer types you've heard of or maybe some of them that you want to see in clinical practice that you've seen already maybe if you're already practicing and there's some really good uh information here so cancer research UK will provide you with Statistics with any cancer type so we haven't covered leukemias for example of course childhood cancers um leukemia is one of the most common so that's one to really look up if you want to work with that group uh there's some general information specific cancers McMillan is very good for the public information it's a great place to start even if you're working in this area because it will provide you with a whole load of information and for UK based healthc Care Professionals the patient doctor UK resource is really good it's for uh general doctors it's not targeted oncologist so it should still be very readable for you guys even though it's written very much in medical language so thank you very much for listening um I will just very quickly summarize in the fact that we've got an increase um in the cancer burden in the UK we know that we are going to have one in two of the UK population being diagnosed with cancer at some point in their lives and this a significant Public Health burden and significant burden that's to the person of course we know that we can have a significant rol and prevention by just actually counseling people picking up on those risk factors and really addressing them at the point where they present to you with ibas or endometriosis or PMS whatever it is and then looking forward to actually going okay I want to be able to say to anybody who comes to me what do the sits look out for I want to be able to have a really good idea of what the red flags are um for both primary and secondary cancer presentations and be able to refer appropriately but to me nutrition LIF place such a huge role as you could probably see in the vast majority of cancer significant component here in terms of environmental exposures so we really need to I think work really hard on supporting everybody who comes to us whether they have any kind of family or personal history of cancer. ________________ 1.2 Cancer Nutrition & Lifestyle Strategies for Cancer Prevention and Risk Reduction Hello everyone and welcome to a talk on cancer prevention and really here we're going to be talking about reducing cancer risk. Just the usual disclaimer, my affiliations. So let's talk a little bit about the environmental factors in cancer. This is a great World Cancer Research Fund report, the extract of which you have on your Thinkific portal and you can access all of this online. But I love this diagram because it talks about The host factors interacting with environmental factors and diet and lifestyle factors all effectively either supporting or inhibiting the cancer process. And that gives us a lot of power ultimately, doesn't it? And gives our clients a lot of power. So host factors, as you can see here, anything to do with genetics and epigenetics, of course, then comes from environmental factors and diet and lifestyle factors anyway. Got microbiome, which is a host factor that's influenced by all of our exposure. as well as things that we can't really change, just like age or gender. Things that are modifiable like metabolic state and inflammatory state and other host functions, as well as all of our environmental exposures from food to infections to UV to various environmental carcinogens, as well as all of the nutrition lifestyle from physical activity, alcohol, nutrient intake, smoking and stress and psycho-emotional well-being. So all of this combined together, host factors are influenced by environmental factors and diet and lifestyle factors, all effectively influencing the cancer process. And it's wonderful to see this in the World Cancer Research Fund report. So World Cancer Research Fund report has over 300 references and has been approved by the American Institute for Cancer Research. And these are the main recommendations they make on cancer prevention. Now, when we talk about prevention here, we mean primary prevention, which means reducing the risk of cancer appearing in the first place. This is different to reduction in recurrence risk because the data might be different within that. So just keep that in mind because prevention or primary prevention is not the same. But if we wanted to actually reduce the risk of anybody getting primary cancer in the first place, then these are the things I would recommend. So being a healthy weight, being physically active. And there are some specific guidelines around physical activity that we all need to be aware of. And these are things like 150 minutes of aerobic exercise of moderate intensity, combined with two strength training sessions a week and some flexibility, adding balance as we age. Then in terms of the dietary factors, I talk about eating a diet rich in whole grains, vegetables, fruit and beans. And this is really all about fibre and phytonutrient intake, limiting the consumption of fast and processed foods. as well as the red and processed meat and particularly avoiding processed meat as much as possible and limiting the consumption of sugar sweetened drinks and alcohol consumption. This is all about harm reduction. And of course, smoking would also come into this as well. They talk about not using supplements for cancer prevention. And really, in a way, this is sort of correct, although a recent interventional trial did show that vitamin D and omega three combination with and A physical activity programme has actually reduced the risk of cancer in older population. And then for mothers breastfeeding the baby if they can and then they also say that most of their recommendation may be relevant to cancer survivors although here really would look at specifically survivorship data rather than looking at primary prevention. So here are the links to the report. There's the full report there. I'd only like you to read a really quick summary of it because that should be enough. But if you really want to dive in, this is the full report. There's an evidence matrix, which is really interesting. It lets you dive into things interactively and evidence of specific cancer types, which you can go away and play with yourself depending on what you're interested in. So talking about fibre, so making sure that we've got a... really wide variety of non-starchy fruit and veg at least five portion really i am quite a bit higher in the minimum 30 grams of fiber and what does that look like so here are some great graphics and that i got online and here from my nutritionist and this is just lovely to be able to visualize for people what does a 30 grams of fiber look like that's what we should all be aiming for and actually you I will be covering that later on in terms of immunotherapy support, but we know that not only will this influence a reduction cancer risk, it can also influence even immunotherapy outcomes in melanoma for example, where a minimum of 20 grams of fibre is required for good response. So this is something we should be aiming for with everybody. Limiting red meat, So really the report advises no more than three portions of fresh red meat per week, obviously the best quality possible, so that's organic or wild, up to 350 to 500 grams cooked weight in divided portions, very little if any processed meat, none is the ideal really. And it's important for us to explain to our clients what is processed meat, because different people have different conceptions of it. Now, Processed meat is particularly strongly associated for colorectal cancer risk and there is an association with red meat as well but there are some other cancers as well so breast cancer risk for example as well as lung cancer risk so this is something that again you can look up and it's definitely worth mentioning diversifying protein sources. So while association is not causation so that's really important for us to know that just because something is associated doesn't mean something causes something. I think it is important to also look at the fact that there are some potential mechanisms, colorectal cancer in particular, where red and processed meat causes actually an increase in different bile acid production because we know it would do so because of the saturated fat soliciting that response. And what's really interesting, there's a paper there for you to read if you're really interested, is that it can cause an increase in sulphur compounds and then the hydrogen sulphide producing bacteria such as the sulfovibrio for example. and will produce excessive hydrogen sulfide. We need some, but excessive hydrogen sulfide can then also increase inflammation, may produce DNA damage and decrease gut barrier function. There's also bacterial modification where there are secondary bile acids that are being produced that actually promote more tumorigenesis in the colon. And there's, again, there might be some bacterial fermentation of choline if you've got the TMA. O producers and that could also result in metabolic disturbance conducive to colorectal cancer. So do have a look at it. And of course, the opposing side of things is we know that physical activity, fibre intake, they all actually modify the gut microbiome in favourable ways that produce the right short chain fatty acid balance. They actually promote gut barrier integrity, promote Treg function. and reduce the exposure to LPS, for example, managing that systemic inflammation. So all really, really important. So moving on, we'll be talking a little bit about alcohol now. So we know there's a number of different solid cancers that have been associated with alcohol exposure and the number of different mechanisms. It could be that alcohol-derived acetaldehyde is a carcinogen that's very well known and documented. It could be that alcohol is inducing inflammation or actually promoting nutrient deficiencies. Again, both of those have been very well documented. So ultimately, it increases the risk of most cancer apart from kidney, which may be protective. There's some arguments about that now as well. There is no level of consumption of alcohol below which there is no increase in the risk of at least some cancer. So just one drink a day has been shown to be strongly linked with breast cancer by the World Cancer Research Fund report. And three drinks a day result in significant increase in liver cancer risk. So it's really, really important for us to be aware of that. So this is some data for Cancer Research UK, which is a wonderful resource if you ever want to grab some good graphics for your handouts or to counsel your clients around. So alcohol, it talks about the seven types of cancer here. So you can see bowel, breast and women and mouth and upper throat being particularly large and also the others. And for breast cancer risk, you can see here that only just up to three units a day, so up to one large glass of wine a day, you could get that with five extra cases per thousand women in the UK. And obviously, the more you drink, the more the increased risk there is. And drinking less alcohol could prevent nearly 13,000 cancer cases per year in the UK. So it's really, really important. So alcohol is a tricky one because it is a socially acceptable drug. So what do we do? So it's important to counsel our clients around this because most people really don't realise the impact that it can have, particularly on breast cancer. How many perimenopausal or postmenopausal women do you know who can put away, you know, either a large glass of wine or up to half a bottle with their partner per night sometimes? So it is really important for them to realise just how much it affects them. It's really important to offer palatable alcohol-free alternatives but do watch the sugar or sweeteners. We talk a little bit about some of the kombuchas and we also advise people to avoid the high sugar ones. Some of the kombuchas on the market, for example, can have as much sugar as a cola, just as an example, you know, 4, 5 grams, 6 grams. of sugar. So it's really important to watch label, to look at brands that are really two to three grams maximum per 100 ml or less. Also watch the sweeteners. So ideally we want kind of minimal sweeteners if they are going to be using them because most no added sugar kombuchas would have been full of sweeteners of various kinds. That's one example. There's various kind of spiritual alternatives such as seedlet, but then you have to watch what mixes people have with them. So there's no one answer for everybody, but I do suggest that you do a little bit of market research and maybe create a handout on alcohol-free alternatives that people could look at. So that might be a little bit of homework for For those who are really struggling to reduce or stop alcohol intake, there might be some interesting resources. So Drink Aware app is very good in tracking your alcohol intake, and it also tells you caloric impact as well as wallet impact of the alcohol you drink. So that's important. And if people are really struggling with it psychologically because of stress or trauma or other things that might be playing into it, then Annie Grace books tend to be really good. And I know Alan Carr has some books as well. So well worth reading those yourself as well so you know what you're recommending. So other risk increase associations so there's various ones here that I'm not going to read through but there's obviously there's some anthropometric things like higher birth weight and adult height adiposity we know is what very well associated with postmenopausal breast cancer so the higher particularly your visceral fat the more The risk there is really because of estradiol production via aromatase, increased inflammation, increased dysregulation of insulin. We know about toxic exposure, so anything from arsenic and drinking water to aflatoxin contamination, one of the main reasons I'm not keen on peanut butter in particular. Salt-preserved foods and as we know avoiding any beta-carotene supplementation in smokers, current and former smokers. Here are some of the mechanisms and I provided the Wiseman paper for you to read if you're really interested in exactly how things are being caused here. So I am going to highlight obesity and cancer because as we know, so many of the UK population are really struggling with weight and obesity. And as we know, it affects all the different hallmarks of cancer, you know, from. Thinking about here breast cancer, things like oestrogen, there's maybe sustained proliferative signaling in postmenopausal women. If there is more adipose tissue, more postmenopausal estradiol circulating around, you can also upregulate the growth pathway such as MAP kinase and ERG pathways. And also that activation of those pathways can also evade the growth suppression that the cells try and regulate it with. We know that the adipose tissue is an endocrine tissue. It's active. It also then pumps out a lot of the pro-inflammatory metabolites. It affects metabolism, so deregulates the energetic, so increases nutrient uptake, alters glucose metabolism and promotes inflammation. And that can be really, really important here. So really, really essential for us compassionately to address. people who are having problems with their weight. And we worry so much about people losing weight during cancer treatment, but actually a lot of people find they gain weight during cancer treatment because they're comfort eating and they've been told they can eat all the biscuits and all the cream buns, just don't lose weight. So quite often we will find that people after treatment, particularly in breast cancer and maybe sometimes in the gynecological cancer, can actually gain weight significantly at post-treatment. So it's important. for us to address that. So our protective links in the reports Mediterranean style diet has been shown to have mainly metabolic benefits also although that is being updated anyway so watch the space. Coffee may be protected for liver and endometrial cancer and dairy potentially for colorectal but you know really here we talk about organic fermented dairy without over-reliance and we do tend to remove inactive prostate cancer. because it may potentially influence that. Nourishing, this is really interesting. I really like that in their full WCRF public health framework, they actually talk a little bit about addressing things on multiple levels. Of course, one-to-one we can address things with clients, but we really need big policy changes. We're talking about changing the food environment, changing the food system, and actually supporting behaviour change, because as we know, just telling people what to do doesn't really work. So it's really important that we have good counselling and coaching skills to be able to support people making the changes they need and help them troubleshoot it. And this is a public policy package of actions needed, which I really like. I think it's really important for us to all engage with that and also advocate for that within public health. So do take a look at that. And it's everything from. Making sure there's healthy food and drink available, to having an incentive in the community, having healthy urban design so people can go for a walk properly without feeling unsafe, to making sure that everybody in healthcare has education and skills to be able to counsel people around this prevention. That's important, of course, we know that doesn't really happen at the moment within the UK. So specific foods and food groups, I am not going to go through everything here, but I have put down a number of different references. A number of specific foods and food groups have been studied for reducing cancer risk. So green tea and a number of solid tumours, brassicas and colon, gastric and breast and prostate, for example. And interesting enough, there was a study around bladder cancer survival. Mushrooms, breast and ovarian, for example, and the signings and colorectal cancer, flavonoids, and all sorts of cancer. What's really interesting here is, of course, you could think about the whole matrix of what you're eating. Rather than focusing on one food group, we need to actually think about how much color can we bring in, then bring in some specific groups like brassicas, green tea, and mushrooms. But really, it is all about having a diverse, fiber-rich. colorful diet and as much diversity as possible and really incorporating things like herbs and spices. And of course all of that is also going to feed our healthy gut microbiome and we know the gut microbiome has this huge influence in cancer and you can see here the microbiota can actually influence different hallmarks of cancer. So for example there are certain bacterial products that might actually increase the signaling that allows proliferation of colorectal cancer cells. There are certain things that might induce more genome instability or promote inflammation. That's really, really important. And we know, for example, Fusobacterium nucleatum, as well as some specific species of E. coli have been linked to promoting the tumorigenic process, as well as some of the others mentioned here. And of course, we know there's some protective things, right? So there are a number of protective metabolites. We know the short chain fatty acids, for example, that actually inhibit the cancer hallmarks we see here. And beyond that, beyond influencing cancer hallmarks, actually gastrointestinal microbiota also influences. You can see not only cancer, but also the influence of cancer therapy in terms of looking at efficacy of various conventional therapies, as well as particularly immunotherapy and toxicities as well. So it's definitely something we need to be paying. close attention to we're going to be exploring more of in module three so here's my uh cancer prevention or cancer risk reduction i should say recommendations really we want to have an anti-inflammatory mediterranean style or other culturally appropriate rainbow diet with 7 to 10 portions of vegetables and one to two portions of low sugar fruit daily and i know that's a lot to aim for for some people so we do it in stages and slowly the emphasis should be on incorporating as some specific families as well. So cruciferous vegetables, allium family, mushrooms, berries, herbs and spices, the more the merrier. Eating organic whenever possible to reduce our exposure to environmental pollutants and pesticides. Healthy fats, of course, extra virgin olive oil, omega-3 rich small wild oily fish, fresh raw nuts and seeds, avocado and avocado oil, and the lattes really might tend to be my preferred cooking fat. small amounts of other fats such as all coconut organic butter or ghee depending on the situation and what people are doing limiting red meat of course no more than twice a week if eating any and avoiding processed meat completely and of course if we're eating grains there should be whole grains and vastly outweighed by vegetables full stop and we should be limiting dairy to organic fermented unsweetened forms such as kefir yogurt Overnight fasting of 13 to 14 hours and it's really mainly based around breast cancer data but it's helpful for us to have a good overnight fast for our gut health as well. We know it impacts the gut microbiome as well as metabolic health. No smoking, reduce or avoid alcohol. Ideally of course limiting refined sugar, processed foods and processing refined oils particularly those seed oils. Talking about avoiding that excessive sun exposure and using sensible sun protection so non-chemical. Reef safe sunscreen mineral based. Hydration with clean filtered water. Quite often people don't know that what they're drinking is full of all sorts of interesting things. Using green tea and herbal teas and coffee in limited amounts after food, depending on someone's individual tolerance. Moving regularly according to the government guidelines, maintaining healthy weight, focusing on reducing your visceral fat in particular. Looking at environmental exposures overall, of course, home, kitchen, cosmetics, air pollution, medications, you know, minimising things as much as possible. You know, ultimately, we don't live in a clean environment anymore. We don't need to be completely obsessive about it, but we do need to try and make an effort. And of course, follow personalised recommendations based on your own clinical history, what your own needs are, what your biomarkers are, and your own unique nutrigenetic background. So that's just my thoughts on the matter. And again, you can see the evidence behind in the reference list. There's some interesting perspectives around pharmaceutical chemo prevention. So low-dose aspirin can reduce cancer incidence and mortality overall, specifically for GI cancers. And particularly in high-risk populations, such as people with Lynch syndrome, NICE does actually recommend considering daily aspirin, although that's quite high doses. So... of course, people will have potentially increased side effects, such as increased risk of bleeding. Professor Kerry Bone proposes actually a herbal alternative, look at willow bark, at least 800 milligrams a day to deliver about 220 milligrams of total salicin. So that's another thought to consider it. And usually willow bark is much better tolerated than high doses of aspirin because it's a whole herb ultimately. Metformin statins have been studied for reducing not only cardiovascular disease and type 2 diabetes, so T2DM is type 2 diabetes mellitus, but may also reduce risk of cancer in this population. And as we know, diabetic side higher risk of a number of cancers, as well as more aggressive presentations and poorer survival. High risk women, there's been some... studies around breast cancer prevention with using CIRMS and their selective oestrogen receptor modulator. So things like tamoxifen and raloxifene, they are FDA approved in the US. We don't see that quite as much here in the UK in terms of practice. I haven't seen any good, nice guidelines around those. But again, watch this space because chemoprevention is part of the current research because of how much cancer burden. we are currently under and the increase that's projected to happen by 2035-2040, which is going to be a public health disaster. So as you can probably tell, we're really working very hard and trying to reduce it as much as possible. What I'd like to see really is much more investment in nutritional lifestyle as a chemo prevention strategy, rather than just looking at pharmaceutical chemo prevention. So thank you very much for listening. I hope it's been useful. I've done a number of different resources for you within this particular module. So do have a look at the World Cancer Research Fund report because there's more information there and that's your homework to read. And there's some optional papers for you to look through as well. And here are some references for you if you're interested. ________________ 1.3 Cancer Screening and Hereditary Syndromes Overview cancer syndromes as a part of the Systems Approach to Cancer programme for nutrition professionals. So today we're going to be talking about the UK cancer screening programmes and then we'll very briefly outline some of the common hereditary cancer syndromes you might come across. So the three main UK cancer screening programmes that are in operation for the vast majority of the population and that's colorectal cancer, breast cancer and cervical cancer. There is no prostate cancer screening with PSA, which is a blood test, because it hasn't been found to be reliable enough, particularly when it's only used as a one-off check. Several areas of England have studied lung health check back in 2019 for targeted screening for lung cancer, and those targeted lung health checks are now being rolled out all across the UK, really. It is taking some time. so not everybody might have this available in their area. In terms of targeting these lung health checks, they're really looking for people 55 to 74, current or ex-smokers, who are registered with their GP, because that's how they can register for that sort of programme. Usually, history-staking high-risk individuals are offered a chest CT scan, and they expand in their criteria, so these can be changed over the last couple of years, and you might have seen some of the coverage in the news about having those mobile check vans as well. So let's look at the colorectal cancer screening programme. Usually in England, there's a one-off flexible sigmoidoscopy offered at 55, and that can be taken up any time between 55 and 60. And then between 60 and 74, those who are registered with their GP get a fit test sent out every two years. It only requires one stool sample rather than the old faecal occult blood test which required three samples. So it's much more convenient and it appears to be very effective. And then people who are over 74 can actually request an additional screening kit by contacting the screening programme if they wish. Of course, if the fit test is positive, someone will have to undergo a colonoscopy. And here is some public health information for you. And of course, if you are non-UK based, you will need to check your own government guidelines, usually from your own national service to look at the screening there. So for breast cancer, really most of the time, the first invitation to a mammography screening would be between 50 and 53. They will take place every three years and then over 71 can also then continue with screening if they wish to. And there's been a lot of concerns around overdiagnosis in particular, because we do know it does lead to overtreatment and can inflict harm. However, at the moment, there is no validated alternative for that. So that's what we've got at the moment. However, there are interesting new approaches that are up and coming. So NHS data suggests that for every breast cancer death prevented, approximately three women are overdiagnosed and treated. Now, that's a death prevented. Of course, that's not a diagnosis. So we know that it's not about just death prevention, but also picking cancers up at an earlier stage anyway, where they can be treated with much more contained therapy as well. People worry about radiation exposure, and I would suggest that it's quite negligible if it's done every three years, but they can be really significant if they're done in intensive surveillance programmes in terms of annually for a long, long period of time for high-risk women. And just to put this in context, a single radiation dose for a mammogram is the same amount of radiation you would receive from your natural environment over about seven weeks. So you can imagine over about three years actually it doesn't seem to be that much radiation exposure, however if it's done annually over a period of 10-20 odd years then that can stack up over time. So we are hoping that instead of indiscriminate screening with mammography we might be able to do We call the risk stratified approach, identify people who are particularly high risk using things like mammographic density. Remember, we told you that women who have denser breasts at a higher risk of breast cancer. So if we can stratify women into low risk and high risk categories using that, as well as some polygenic risk scores based on the SNPs they have. And these are multiple different SNPs. This is not just one or two things you might detect. In some of the typical nutrigenomics things that are available to you, these are big risk scores that are validated at really large population level. And usually they will include anything from 18 SNPs up to, say, 100-odd SNPs. And there's a paper there for you if you're interested in one of the publications that was recent. And there are other things that we might want to look at. We might want to look at other modalities. Instead of mammography, can we do something different? Can we do automated ultrasound? Because part of the problem with ultrasound is that it depends on the operator quite heavily. So if you have an inexperienced operator, you can miss cases. MRI, but then MRI again has its own problems in terms of... contrast in terms of the length of exposure, people get claustrophobic. So at the moment, there is no really perfect way of doing this, and there probably won't be. You'd have to have risks and benefits to every approach. What's interesting as well is you might also come across a new approach that's not a validated screening tool yet, but is an interesting approach in terms of home checks. So like we discussed about checking your breasts, actually There's been a pilot of a device that can actually scan your breast every month at home and then tell you if it detects any changes over time. And that would encourage you to go to your GP and go through the normal channel. So it's not a substitute for going to your doctor, but it could be potentially quite an interesting at-home use tool. However, it has not been validated to have sufficient sensitivity and specificity for diagnosing cancer yet. So watch this space. Cervical cancer smears are offered to women 25 to 64, usually every three years up until the age of 50, and then every five years. That's because usually predominantly cervical cancer, unlike many other cancers, is a disease of younger people. So HPV triage, the human papillomavirus triage for high risk variants, which usually things like 16, 18, 31, for example. is now being used at the beginning rather than looking for cell changes. We used to look at dyskaryosis or cell changes first and then test it for HPV. We're now doing it the other way around because it's been shown to be more sensitive and accurate. So if the sample is negative for high risk HPV, there will be no further testing. They won't look at the cells and you'll just go back to being recalled every three or every five years, depending on your age. If it is positive for high risk HPV. They would normally also test the sample for cell changes and what's called dyskaryosis. That's a change in the way the cell looks and behaves because that's usually an indicator that there might be what we call CIN or SYN. That's cervical intraepithelial neoplasia. That's a kind of a precancerous condition. It comes in grades one to three, with three being the highest and the worst. And we want to be able to pick it up at that stage and be able to usually cut it out with effectively a loop diathermy. There's effectively a cauterization that happens so that it doesn't progress to actual overt cervical cancer. So if there are cell changes that are detected after you've been tested for positive or high risk HPV, usually there's a colposcopy where the gynecologist will take a look. and they might actually take a further sample or they might do an intervention, like I said, a kind of a loop excision, for example, if they can see a clearly defined abnormal area. If there are no cell changes, you just go back to cervical screening. But instead of going back every three to five years, you first go back annually until you clear the HPV, for example. And there's no further cell changes. And there's some information here for the cervical smear test program. In terms of emerging technologies, there's a lot of interest, and surprisingly, with our increasing cancer burden in using more convenient pan-cancer, so multiple cancer-type screening tools. And there's currently an NHS pilot using the Grail Gallery test that's based on cell-free DNA. So our cells will put out various amounts of basically free DNA into the circulation that can be detected through a blood test. And... What we would want to see is we'd want to see any patterns that suggest cancer, and that's what the Grail Gallery does. However, the problem is that the recent ESMO conference has shown to have quite a high false positive rate. So you could imagine there's quite a lot of harm that could come from that in terms of using up NHS resources, going through the motions of trying to diagnose cancer that isn't there, for example, not to mention the psychological and physical distress for people who might have been identified as positive. So there's definitely some questions around this particular test at the moment. It's a move in the right direction of having a more inclusive, wider pan-cancer screening program, but the question is, is this the right technology really? And there are other technologies available. So they're circulating tumour cell based, instead of looking at the fragments of DNA that are circulating around, can we look at circulating tumour cells? And these are things like data cancer genetics, TrueCheck or Trinetra in the US. And again, you can diagnose really early cancers from that perspective. And that's been given a breakthrough designation by the US regulatory authority, the FDA. And certainly something that we use in clinic. There are limitations to any liquid biopsy, so any cancer detection or cancer monitoring tool that's relying on a blood test. There is no single test that can detect every single cancer type. And normally they're targeted as solid tumours, so most of these will not diagnose blood cancers. And it's really important to know that just because you're given the test, of course, you need to have really careful counselling around the people need to expect they might get a positive result and people need to expect the investigations that would be required and if for example there might be in a private setting then the private costs that might be needed in the treatment and usually if we would get a positive test results with something like true check in our practice we would refer both ways we would refer by the private route because we've got good connections in the oncology community but would also refer back to the gp so they could go through the nhs and they can then choose you where they can have their treatment as they go through the process, really. It's also important to know that no test is perfect, of course. We assume that the results as a result, well, actually, there's false positives and false negatives in all tests. Although, of course, there's more things like false positives in tests that are based on things like cell-free DNA than usually with a circulating tumour cell test. And it's important to also know just because at that point, point in time someone didn't have cancer, that doesn't mean they're not going to develop that over the next five, ten years. So it's important to continue doing these tests serially, what we call them, so at multiple points in time rather than at one specific time point. So that's most effective really. So we've finished the screening programmes, we've outlined the main three cancer screening programmes as well as the targeted rollout of the lung health checks. as well as talking about some of the emerging approaches. And now we're going to talk a little bit about the hereditary cancer syndromes. So the relatively common hereditary cancer syndromes would be things like BRCA1, BRCA2, some of these things that you will have heard about or Lynch syndrome. And there's some less common ones that I will very briefly outline that you can read up on. So usually when somebody's been found to have a hereditary cancer syndrome, Don't forget they might not have any family history because they might be the first person with this mutation that can be inherited. So it can be patient zero effectively. Some of them of course will have extensive family history and that's why they got tested in the first place. Usually in hereditary cancer syndromes they will undergo intensive screening, they might try what we call chemo prevention, that's giving medication to try and reduce the amount or the risk rather of cancers developing. or risk reduction surgeries where they're applicable. So with BRCA1, BRCA2, they will confer increased risk of breast and ovarian cancer and also have other cancer risks as well. Anything from prostate cancer with BRCA2, for example, at 20-25%, male breast cancers and several other cancers that you can look up in the Royal Marsden Hospital RMH guide for additional reading. And it's important to know with BRCA1, BRCA2, There is a significant lifetime risk, really 85 to 90% of women will develop breast cancer by the age of 80 if they haven't been treated in some way. And it's relatively rare in the general population, but can be common in specific population who are susceptible to what we call the founder effect. And that means that their populations, who, for example, may be based on islands or maybe have a lot of intermarriage. And that means that the one individual with the single mutation can spread it through the community quite a lot, really. So they tend to be contained populations that this founder mutation that can get passed around. So Ashkenazi Jews is an example of that, where one in 40 of Ashkenazi Jews can be a carrier for BRCA1, BRCA2. And they have targeted programs for that. And usually if you're positive for one of those mutations. You'd have annual screening from age 30 with various modalities. So what is BRCA1, BRCA2? Most of the time people will talk about it, but they don't actually know what it is and what those genes do. So they actually play a very, very important role in repairing DNA damage. And this is a particular type of DNA damage called double strand break. So as we know, DNA is double strand. double-stranding molecule and when it breaks you have floating free ends which are very dangerous to a cell and ultimately a certain amount of DNA damage will be lethal to the cell. So the cell will try and repair it. So we use a process called homologous recombination, you don't need to worry about it too much, but that's one of the really accurate processes to try and repair the DNA breaks by using a pair copy. We know our chromosomes come in pairs. Using the homologous pair, to try and copy and repair the break. And this is where BRCA1 and BRCA2 come in really. When the damage is being sensed, then a big, big protein complex, like a helper complex, gets recruited to the DNA break, and BRCA1 and BRCA2 are key proteins within that. So mutations within those proteins means that the mutation within those genes basically change the protein function. So it means that that repair is less efficient effectively and that can predispose you. to increased risk of cancer. So if you remember nothing else really, BRCA1 and BRCA2 are genes whose products are involved in DNA repair, particularly repairing double strand DNA breaks and that's all you really need to know from that perspective. So another relatively common hereditary cancer syndrome you might come across and again I say relatively common I mean they're still really rare compared to the general population vast majority of people you'll come across will not have a hereditary cancer but HNPCC or hereditary non-polyposis colorectal cancer that's also known as the Lynch syndrome tends to predispose people to early onset of colorectal cancer and endometrial womb cancer as well as various other tumours particularly ovarian And quite often when women reach their reproductive goals, most women with Lynch syndrome will undergo preventative surgery. So they will have the total hysterectomy and removal of both ovaries. So we call that TAH and BSO. That's total abdominal or laparoscopic hysterectomy, depending where you're at. And BSO, that's bilateral sulpingo-oophorectomy. All it means is removing both ovaries and fallopian tubes. So effectively they would have... those reproductive organs removed to try and reduce the risk of effectively getting those cancers, endometrial and ovarian cancer, which can be very, very deadly, particularly ovarian. So what is the Lynch syndrome? What is it caused by? Well, it's caused by mutations in, again, the DNA damage repair pathways, but this is DNA mismatch repair genes. So this is a very different pathway to repairing double-stranded breaks. And there are four different genes usually involved, so MLH1, MSH2, MSH6 and PMS2. You don't need to worry about what they are, you just need to know that it's not one single gene that's involved here, there are different genes that are involved in DNA mismatch repair and that's what predisposes you to increased risk of those cancers. And I've also put in the Royal Marsden Hospital or RMH guide for you to read up about it. So effectively, When we have a normal mismatch repair, we can identify when one pair of the genetic letters doesn't match the pair on the other strand of the DNA. We can repair it quite quickly. But if we have a mutation in any of those four genes in the DNA mismatch repair pathway, that means you don't have the right tools. You can't really repair it properly. So you would get a mutation instead of a correction. And that can predispose you to increased risk of cancer. So various less common hereditary cancer syndromes, I'm not going to read through it, you guys can do it in your own time. They're all really quite rare, but many of them come with a significantly higher cancer risk. And of course, anytime an individual is identified to have this kind of syndrome, you have to think about the impact on the family. You know, sometimes it might be passed down a certain line, like it might be passed on, the risk might pass on just female members, for example. Or it might be that everybody in the family could be affected. So that could result in quite a lot of genetic testing for the family. So this is not a trivial thing. None of those tests are. So it's not a willy-nilly thing. I'm going to go and get tested for BRCA1, BRCA2, because it doesn't just affect someone who wants to know. It also affects people who may or may not want to know. And that's why in the NHS, there are really detailed genetic counselling programmes that talk to you and members of your family about what the process involves, what might be offered if you're positive for some of those mutations, because there are consequences to those. As you know, BRCA1 and BRCA2 will be quite often offered a double mastectomy and oophorectomy, so ovarian removal, as well as prophylactic surgery, and they might be offered other things as well. So it's really, really important to understand that this is not a... quick tests that you could get online. You could get some of these tests online these days, but the consequences are profound and can be severe for the person involved and their family, and it cannot be taken lightly. It's really important. So thank you for listening. I hope you found this session on the cancer screening progress and hereditary cancer syndromes really useful, and do look up the extra reading, and I'll see you in the next lecture. ________________ 1.4 Comprehensive Overview of Cancer Theories & Hallmarks Of Cancer Welcome back to Systems Approach to Cancer Program for Nutrition Professionals, Module 1. Today we'll be talking about cancer theories and hallmarks, and I'll also introduce something about cancer staging and grading and the way that cancer treatment works within the NHS in terms of the multidisciplinary team. So, usual disclaimer, so we're going to start with the somatic mutation theory of cancer, and that's the predominant theory that's really been dominating the cancer research field for quite some time. And this theory supposes that cancer begins with a genetic change in one single cell that kind of they all accumulate over time and gets passed on to its progeny, thereby generating a clone, which is kind of a collection of malignant cells over time. So it means a single cell gets a mutation, passes it on to the subsequent cells when it divides. the mutations continue to accumulate and then cancer results out of that. And there's some key concepts around oncogenes, which are the genes that can promote the cancer process. So when they're normal, they're called proto-oncogenes, they haven't become oncogenes yet, but when they have mutated to be conducive to the cancer process, they're called oncogenes. And there are tumour suppressor genes, they're kind of the brakes on the system and ultimately When they get mutated, they usually lose their function. And then again, that allows the cancer process to proceed. And one of the examples of these stepwise changes leading to cancer has been shown to be present in colorectal cancer. So, for example, what we can see, because we can actually take little polyps out of people during colonoscopies and we can actually monitor them, we can monitor their development over time as well. is that we can see that there are stepwise changes of course also we've got the animal model studies to show us those as well. So for example in a normal colon that might be first hit acquired in a tumor suppressor gene and for example here it would be APC. So for example on something at chromosome 5 where the APC gene is located either mutated or you acquired a defective copy from your parent. Then there might be an activation of a second copy of that gene, and now you've lost that normal function. That means the cancer process can kind of start actually taking off effectively. And that's what's called the mucosal at risk. It's where you've lost some of the essential function. Then they can get a proto-oncogene, which is a normal gene that can become an oncogene, a mutation in that. So KRAS is one of the examples of those genes. And when that gets mutated, then you actually start getting the growth. of more of a benign polyp, so called an adenoma. And then as you progressively get more and more mutations accumulating, so P53 is a guardian of the genome. It's heavily involved in detecting DNA damage and problems within the cell and then asking the cell to commit suicide. That might be lost. You might get other driving mutations. You might get telomerase, which we'll talk about a bit later. So immortalization of the cell. And then that progresses to effectively carcinoma. So that's reasonably well established in terms of the progression in colorectal cancer. And there are other cancer theories that are emerging. And that's, I think, really, really promising because somatic mutation theory doesn't actually explain a lot of the issues that we're having. It doesn't explain all the experimental findings that we have. So one of the examples is tissue organization field theory. And that actually tells us that potentially. All cells, their whole default state is to proliferate. In fact, it's only the interaction with their neighbors that stops them from proliferating abnormally. So where there is an abnormal interaction between the supportive tissue, we call stroma, and the functional cells of the parenchyma, then that means that actually they are then allowed to go off on their default proliferation program and there's no breaks in the system. And that's quite interesting because this views cancer is potentially reversible, if we can restore some of those normal control mechanisms from the surrounding supportive tissue, could we halt the cancer growth effectively? So that's an interesting theory. Metabolic theory really views cancer as a mitochondrial metabolic disease, and you can watch the video on that. Against the promising things, it certainly doesn't explain everything either. Here are some examples of comparisons between SMT, which is somatic mutation theory, which is that thing of going, we're going to get progressive accumulation of mutations leading to cancer, and comparing that with the tissue organization field theory or TOFT that tells us actually it's not about the DNA mutation. mutation change. It's about the whole tissue becoming dysregulated and those interactions giving rise to cancer. So it's quite interesting. There's strengths and weaknesses of both, and you can read up a little bit about them if you wish. But I tend to find that the later theories are certainly tough, and some of the evolutionary theories are quite interesting. Metabolic theory of cancer has been started really by Warburg, and then by... picked up by Seyfried in particular, and that views cancer as a mitochondrial disease. And again, there is some experimental evidence that definitely holds within that theory either, so I really wouldn't take that as a gospel. My feeling is that it's a lot more complicated than what we think, and actually it's probably going to take a combination of theories that are aligned to be able to explain cancer as a process. But here it basically views the fact that the cancer comes mitochondria. That's why you get the Warburg effect where you can get glucose being metabolized abnormally and then that leads to effectively cancer. And then they've tried to prove it through saying that actually, if we're going to transfer the cytoplasm with the abnormal mitochondria and then put a normal nucleus in it, it means that there's no genetic mutations. Actually, that becomes then carcinogenic. But you've got to remember, you're going to have to be careful. Most of these studies that are done in cells are not done in proper tissue. And that's why it's really important when we study cancer, we use the right models. Cells on a plate, they cannot model normal tissue. We need normal tissue interactions. And there's a lot of really interesting work that's been done on what's called organoids, basically architectural constructs where you can put in the supporting tissue as well as the cancer cells. And then you can effectively almost try and replicate a mini organ or a mini tumour. And then that's going to give us much more reliable results than just looking at cells and culture, because that's not the way that actually tumours behave. They're really complex, organised entities, not just a lump of cells effectively altogether. So there's another theory, which again is really promising, is called CETOC. It's Systemic Evolutionary Theory of Cancer. cancer pathogenesis. Really what it says, and to me, this is really interesting because I really like that combination of looking at the behavior of the tissue, but also the uncoupling of the metabolism bit. So what it says is there might be an insult such as chronic inflammation or exposure to some kind of environmental stimulant. That then leads to the disruption of normal tissue architecture. And then that also then leads within the cell, the uncoupling between a normal cooperation between the nucleus and the mitochondria. So it means they go off in their different ways effectively and they will start activating their evolutionary programs. Because remember, mitochondria or the energy factories in our cells actually originally came into the cell. We didn't have them. So they have their own DNA, they have their own components. So this uncoupling basically results in emerging of this kind of proliferative behavior in tumor cells. And I find it really fascinating. To me, this is something that we really need to watch. And what I love as well is the paper that looks at it also talks about potential benefits of integrating effective blends of natural compounds With the anti-cancer therapies that we now have, with the other beneficial practices like fasting, for example, they can help us modulate those cellular functions, try and get them to reintegrate properly. And actually, this theory looks at modular treatments associated with different cancer processes in the whole ecosystem. So to me, this is really, really promising as a theory, and I think we should be watching that space. And because it looks at metabolism, it looks at the tissue architecture and the way that... things interact as well as the intracellular mechanisms. But again, it's interesting because I think people, most people are so focused on the somatic mutation theory has been dominating the field. People don't realize there are many other theories and also the metabolic theory isn't the only other theory either, which is probably again being popularized to be the only other component. So if you want to know more about the different views of cancer, here are a few books and they all kind of take it from a slightly different angle. So I think what I'd like you to take out of that is that actually we haven't got cancer figured out from the scientific perspective, otherwise we would be much further along. But what we do need to look into me is the kind of ecosystem view of it rather than taking it down, working at the nucleus level, looking at those mutations. Yeah, that's useful, actually, that still does have some uses to it. But we know it's not the full story. And looking just metabolism is not the whole story, because we know immunotherapy doesn't actually it's not a metabolic treatment, but it can work absolutely dramatically. We need to look at the whole ecosystem and actually Also, look at the combination of treatments, not just blasting things with chemotherapy, as we have been for quite some time. We're now going to move on from the more overarching theories into the hallmarks of cancer. And really, they've been designed by Hanahan and Weinberg as a kind of organizing tool around our thoughts in cancer. So there were originally six hallmarks which talked about sustained. proliferative signaling, which means sustained multiplication of cells. Basically, the cells always on and dividing, dividing, dividing. Then there's evasion of growth suppressors. So remember those tumor suppressor genes that want to put the brakes on division. They're not working. The cells gotten around that and so the brakes are off and it continues dividing. Then there are certain processes might activate invasion and metastasis, for example, and that's, of course, invading the surrounding tissue and then going off, spreading itself around the body. Telomerase, for example, in terms of enabling replicative immortality. And that means that there's usually a limit on how much cells can divide, and then you've overcome it and you can divide forever, effectively. Inducing angiogenesis, which is the growth of new blood vessels to supply the tumour with oxygen and nutrients. And resisting cell death, because most of the time when the cell is not behaving as it should do, there are checks and balances within the cell that would tell it no. you've become abnormal, go off and commit suicides as programmed cell death called apoptosis that we would need to activate. So these are the first six. And really, you could group different cancer pathways underneath those and you could effectively study those different hallmarks separately. So it's a very useful organising tool. Then later, there are four other hallmarks that are enabling. characteristics that have been added. And then this is really taking into account metabolism, so deregulating cellular energetics, then talking about the immune environment of the tumour, avoiding the immune destruction, which is really, really important. Of course, that's what a lot of our immunotherapies, including things like immune checkpoint inhibitors, that's where they act. And then enabling characteristics are things that kind of put the fire under the cancer process. So things like genome instability mutation, that means that when there's genomic instability, you can continue to mutate and tumour promoting inflammation, which is very relevant for us because it has a relevance for some of our patients with autoimmune disease, which is why they're predisposed to having a higher cancer risk in their organ that's targeted by autoimmunity because of all that inflammation. But also it has relevance to us looking at systemic inflammation and trying to reduce that. because we know chronic low-grade inflammation is dangerous in this setting. So this is just an overview of all of them put together here. And then there's the 11th factor. And really here, what was highlighted was the importance of the tumor microenvironment. So again, instead of just looking at the tumor cell, just looking at the tumor cell mutations, let's zoom out. Let's see the city of the tumor. And it is like a city because it's not just the cancer cells that are growing. There might be some cancer stem cells, the things that effectively breed other cancer cells, and they can also go dormant and sort of quieten down and just sit there for ages and then can give rise to recurrences years later. There are also immune cells that might be suppressed in the tumour microenvironment and might actually be co-opted to facilitate tumour growth. There might be blood vessels, of course, supplying oxygen nutrients to tumour, but it might be fibroblasts or connective tissue cells that could be actually again being co-opted by the cancer cells to help themselves. So it is a city, it's an architecture, it's not a bag of tumour cells, it's much, much more complicated. And the tumour microenvironment is absolutely essential. It can be conducive to tumour eradication, or it can be conducive to tumour growth. So this is just a few details about each hallmark, and I'm just going to cover them briefly. You don't need to know a whole ton about it, you just need to know roughly what those are. So Sustaining proliferative signaling proliferation is basically multiplication of cells, as you know. So there are, as we discussed, there were genes called proto-oncogenes that are normal cellular genes. And then when they mutate, they actually promote growth of cells without having any kind of growth factor signal. So usually cells would. kind of sit tight effectively until a growth factor goes, come on, you go off, you grow and divide. Now, when we have the mutation, that oncogene drives that proliferation without having any external signal. So usually those particular genes are growth factors, so growth factor receptors, so things like EGFR, et cetera, and I'll show you all components of the signaling pathway. And this is just an example pathway. So you can see the EGF, that's epidermal growth factor, binds to EGFR. And that's a relevant pathway in things like, for example, colorectal cancer. And then that activates something called PI3K, which is PI3 kinase that then goes off and phosphorylates things. There's lots and lots of different steps, including activating mTOR. And effectively, all of that combination of activating multiple pathways. will result in proliferation and resistance to apoptosis and survival etc. So as you can see the multiple steps, you don't need to know any of those, but you can see that there are multiple opportunities for different mutations or activations to occur within that pathway. So, for example, if you mutate the EGFR protein, you don't need the EGFR to bind to it anymore. It can just signal and go off by itself. You can have a PI3K mutation, which is very relevant for a number of tumours, and that will then go off by itself without needing a GFR to go off, and that will drive everything via the PI3K-ACT-M2 pathway to sustain proliferation and growth. So effectively what this hopefully shows is multi-step pathways that could be mutated from proto-oncogene to oncogene that could effectively drive proliferation. Again, this is very much a somatic mutation theory based idea, but it is still relevant, certainly in terms of targeted therapies at the moment within cancer treatment. Here are some oncogene examples. Again, you don't need to know all of them at all. You just need to have a little scan through them just so you know roughly what they are. And they're targeted therapies, as I mentioned, targeted against, which is why we still want to. be mindful of that, even though there are emerging theories that explain some of the other things better. So ERB-B2 is also known as HER2, and you might already know that targeted drugs against that, injectable drugs such as heseptin or trastuzumab and perjeta or pertuzumab. EGFR, there's multiple targets for that in terms of drugs, so based on different mutations, so cetuximab and panetumumab are the most common ones that are used in colorectal cancer. And VEGF is more relevant for another hallmark, but effectively they're also drugs that target against angiogenesis and the growth factors involved in that called VEGF that are also used down the line. And there's many more. So apart from just looking at the growth factor receptors, you might also be inhibiting downstream things. So mTOR, for example, everolimus is used in breast cancer. BRAF is part of the RASRAF. MEK-ERK type pathway, again, a proliferation pathway on the other side of what I've illustrated. And that's used in melanoma with a specific mutation called V600E. And actually, it's incredible. That was a major advance where metastatic melanoma with this kind of mutation would be completely deadly. And actually, the survival has improved massively since we're able to use some of these targeted drugs. So some really interesting things here. Evading growth suppressors, as I said, the first bit of sustaining proliferative signaling is that effectively gas on. You've got proto-oncogene to oncogene mutation, for example, trying to drive that proliferation process. And then you need to also take your brakes off. Otherwise, you're not going to go very far. So the tumor suppressor genes or TSGs are effectively the brakes that need to be taken off, need to be mutated to lose function. And so for. Proto-oncogenes usually gain function, they gain extra oomph effectively to be able to drive proliferation. For tumour suppressor genes, it's the opposite. They need to lose function, so you need to take the brakes off. And these are things like RB, P53, for example, many things that are kind of checkpoints that want to prevent this uncontrolled growth that you lose. And here are just some examples here. We talked about APC. P10 is one of the ones that is involved in. putting the brakes on the PI3 kinase pathway, P53 is mutated in a vast majority of cancers actually, and most human cancers over 50 percent and it's a major guardian of the genome which will find out about later. So we've put the gas on, we've taken the brakes off, the cell's proliferating, but it sustains some DNA damage. And actually, normally, when there's enough DNA damage, the cell gets told to commit suicide by programmed cell death called apoptosis. And this is where p53 really comes in. So because when we've got stress, radiation, chemicals damaging our DNA, p53, when it's normally functional, would go off and say, no, you need to commit suicide. So it will adjust the balance of the different proteins within our cells and tell the mitochondria to initiate the apoptosis program, the programmed cell death, at which point they will release something called cytochrome C and APAF1, and that will ask the enzymes called caspase within the cell to go off and chew everything up. And effectively, that will go off and chew up most of the cell. And then the cell will get packaged up in little vesicles and will basically get destroyed. And apoptosis is a very neat death, effectively. It's done in a controlled way. Unlike necrosis, which quite often happens in the center of tumors, where there's not a lot of oxygen and really cells die very messily. So apoptosis doesn't generate too much inflammation. It's quite a controlled cell death. And if it's functioning normally, it's really protective for us in terms of cancer development. But of course, if we lose components of that pathway, if we get mutations along those lines, we've lost P53, etc. It enables those tumour cells to escape normal induction of cell death. So as I mentioned, P53 is really important. But there's also this BCL2 gene, which you can see back here. And that's an anti-apoptosis gene, that's anti-death gene, effectively. And when it's been upregulated by tumours and mutated in tumours, then actually it protects them again from death. So next bit is about telomerase. Usually human cells will divide for 60 or 70 doubling times, and that's it. You know, they become senescent, they kind of go quiet, you've had enough. A little bit like retiring. They've done all of their jobs, and that's it. And usually this has been ascribed to shortening of telomeres. So each chromosome has caps on the end called telomeres that will shorten the more the cell divides. And when they reach critical mass, the cell will go senescent. It will go to sleep effectively. I'm not going to divide anymore. So most tumour cells will upregulate telomerase, which then repairs those caps. And it means that they can continue dividing and dividing and dividing effectively. And that's called replicative immortality. Now, as a tumor grows, it can't grow beyond a certain size, which is actually a very tiny size, until it recruits some new blood vessels because it needs to be well supplied with oxygen and nutrients. So angiogenesis is the growth of those new blood vessels to supply the tumor. And again, like anything in nature, you can probably tell by now there's activators and inhibitors of most processes. And we call it the angiogenic switch. So normally the angiogenic switch is suppressed effectively. You're not going to get new angiogenesis happening in a normal setting. So normally that would get suppressed. And when the tumour starts growing, it will effectively try and switch it on. So it will promote secretion of things like VEGF. which is vascular endothelial growth factor, or BFGF, which is fibroblast growth factor. Basically, both of those flip the switch. They will go, yes, we want more of those new blood vessels. And they will recruit those cells that build blood vessels into the tumor to start building those. So it's really important. And those particular factors can be either produced by the tumor cells or by the cells. that the tumour cells have co-opted, so inflammatory cells or other tissue cells. So this way cancer is very very clever, it's not just the cancer cells that are doing these things, they actually are co-opting normal tissue architecture to help them. So invasion metastases, that's of course the key thing, without this hallmark you do not have a malignant tumour, okay, you will have a benign tumour, you may have something that will, you know, dividing might cause some local effects by compressing the surrounding. tissue but you do not have a malignant tumour. Invasion and metastasis are what characterises cancer. So really here most of the time the cells within tissues will be contained within their container by something called the basement membrane. It's a little bit like effectively a sack you know you've got something in a bag this is the tissue. Now what happens is that actually Actually, the tumour cells will first of all change their phenotype and they become creepy crawly. They will go off, then they can break through the basement membrane and then pass into the circulation that's called introversation, so getting into the vessel, and then will travel around the circulation and they will attach at usually a specific organ, a specific site, come out, and then they will have to survive within that organ to promote effectively a formation of a metastatic. clone. So that means there's now, for example, in breast, there would be those breast cancer cells going off, breaking into lymphatic vessels as well as blood vessels going off and traveling, for example, to the liver or the lung and forming metastases. So to enable it, as I mentioned, they kind of, the cancer cells are thought to become the creepy crawly cells instead of the stationary cells. So this is called the epithelial mesenchymal transition of EMT. In solid tumours, of course, we're not here talking about blood tumours because those blood cells are circulating in and of themselves. They don't need to become creepy crawly. So the invasion of the extracellular matrix, which surrounds the cells, really kind of initiates that metastatic cascade. First, you've got to be able to move and invade through the surrounding tissue to get to the blood vessel or lymphatic vessel to spread. So first of all, the tumour cells kind of free themselves up a little bit and the adhering proteins are involved in that, for example. Then they need to digest the jelly-like matrix they sit in to be able to move through it. And this is where we have MMPs and they're called matrix metalloproteinases. These are the enzymes that can cleave the different parts of the matrix to enable cells to tunnel through. Then the cells need to be able to attach to these different components to creep through it and then migrate. So that's what effectively EMT is all about. And there are various MMPs involved. What's also interesting is that even before the tumor then starts off going off into the circulation and maybe traveling around trying to land, there's a grooming that occurs. Actually, the tumor starts secreting various. metabolites that might form what we call a pre-metastatic niche. It sort of grooms the organ where it's going to land with various things. And these are the key components. Don't worry about the molecular side of things, but effectively, the pre-metastatic niche is created by the tumour-derived secretive factors, like I said, that are pumping things out into circulation. Then they're also mobilising and things from the bone marrow to help them. They're mobilising and co-opting normal tissue within that organ and that enables them to then, when the tumour cell does decide to land there, to effectively grow and proliferate and be successful in forming a metastatic deposit. So they would immunosuppress the tissue, that would create more local inflammation. We talk about angiogenesis or increased vascular permeability, so more leaky blood vessels so that cells can exit. They might want to also recruit some of the lymphatic cells within that. And there's basically a reprogramming that occurs within that organ to make it a susceptible niche, a little bit like building a nest, right? So the tumour secretes its various factors and co-opts the normal tissues and normal immune cells and bone marrow cells to help create a nest for it when it lands. And that's why what's quite interesting is, of course, different tumours have different organotropism. So they have an affinity for specific organs they might want to land in. The next hallmark is around deregulated cellular energetics. And here we talk about Warburg and reverse Warburg effects particularly. And really, these are really important. They're not just about kind of using glucose to produce energy. And it's not about defective mitochondria, actually. We've moved quite a lot past that after what Warburg has discovered originally. Really, it's about reprogramming the whole cell to increase the uptake of all the nutrients, then increase the synthesis of all the different building blocks that you need to make new cells within that tumor cell, and also have a metabolic interaction with the microenvironment by, say, pumping out lactate. into the tumour microenvironment that suppresses the immune attack on the tumour. So it's a very, very clever and extensive process. So the Warburg effect is the increase in the rate of glucose uptake and the preferential production of lactate instead of the normal oxidative phosphorylation process, even where there is oxygen. So originally when Warburg thought about it, he said, no, it's because the cancers... don't have enough oxygen, there's a defective mitochondrial production of energy, so that's why cancer cells do this. Actually, it's more complicated than that. There's an advantage for cancer cells to reprogram their metabolism like that, because actually by using the Warburg effect, by going from glucose to pyruvate to lactate, they can pump out lactate and suppress the immune cells that are trying to eradicate the tumour. They can also then use the mitochondria not for energy production, but for pumping out, building blocks for making new cells as the cell divides and makes more copies of itself. So there's multiple, multiple interesting things that go on within that that then confer an advantage in terms of malignant progression and survival of the tumour. So here's a bit of information for you here and there's plenty of papers if you want to read about it. So Warburg, okay, fine. What is reverse Warburg? So reverse Warburg is actually where it's the cancer cell isn't doing this, what we call aerobic glycolysis, isn't actually pumping out lactate. It's the stromal cell, the supporting cell called the cancer-associated fibroblast or CAF that's doing it. So actually it's enabling the cancer cell. So it's supporting it. And what's really important to also understand is people have kind of been focusing on the Warburg effect and they assume that all cancer cells do it. And it's just not true. Even within the same tumor, cancer cells might have different metabolisms. And that's where some of the enabling surrounding tissue, that tissue architecture is so important, because that cancer-soluble fibroblasts can then be pumping out lactate to suppress the immune attack, even if the cancer cell is doing a normal metabolism, for example. So that's reverse Warburg and it is associated with worse prognosis in breast cancer, for example. So don't worry about this too much. I know there's a lot of information here, but really all I want to show you is that within the Warburg effect, the key things are is that by doing this aerobic glycolysis, we're not just producing energy and producing lactate. We actually are creating conditions for the building of all the building blocks you need. to make a new cancer cell, nucleic acids, proteins, lipids, etc. And you can see that this is where mitochondria get co-opted into doing that. And as a part of aerobic glycolysis, we also get something called NADPH, which is also really important in terms of generating those building blocks. So that's really, really important. So we don't do... Warburg because the mitochondria are irreversibly damaged. They're not at all. They actually co-opted to make building blocks for new cells. mTOR, I've mentioned mTOR already when we looked at the PI3 kinase pathway where the EGF, the epidermal growth factor bound to its receptor, activate PI3K, and then it went through the different steps to activate mTOR. But effectively, mTOR is one of those major nutrient sensors. and proliferation sensors in the cell. Particularly, it wants to effectively build, build, build. So there are a number of influences on it. The PI3K pathway, like we talked about before, and there's also inhibitors on it. Like everything has a balance. It has to have some inhibitors on it. And AMPK is effectively the brakes on the mTOR pathway. And so it can be effective things like nutrient supply, you know, amino acid supply in particular can be also affected by fasting, etc. So there's a number of things here that we might want to consider. And we're going to be covering a lot more of that in module four when we talk about metabolic health, in particular mitochondrial impact. So we've done a metabolism bed. Let's talk about the immune destruction. And this is really where the vast majority of the advances in cancer treatment has really come from more recently. So immunotherapy really targets this particular hallmark. And what we've realised is, of course, tumours are very clever. Usually the tumour cells would be identified and weeded out by our immune system, but they actually actively try and promote escape from that process. So the number of metabolites that either the cancer cells themselves or their co-opted bodies from the tissue might secrete. So we talked about lactase generating an acidic environment within the tumour. That's not the whole acidic alkaline balance stuff. This is within the tumour vicinity, at really micro level. They might be secreting things like, you know, kynurenine, PGA2, adenosine, other things like that. Hypoxia, so have... deprivation of oxygen within a tumour would also promote that kind of immune escape. And then it means that you can also secrete those immunosuppressive cytokines. So effectively, the environment is not conducive to attack. And also you're secreting cells going, don't attack, don't attack, don't attack. Those messages, for example, like IL-10 will be immunosuppressive and will prevent the normal function of elimination of tumour cells by the immune system. And there are different immunostimulatory nutrients that could also be changed as well. But effectively, what you need to know is that the tumour cells and their co-operative bodies within the tumour environment are trying to suppress normal immune cell function. They're trying to effectively get the immune cell to lie quiet while they go off and proliferate and cause trouble. And a lot of the immunotherapies, including things like checkpoint inhibitors, try and take the break off that inhibition. for example, to then elicit the tumour destruction by the immune cell. So the other one is genome instability mutation. And again, we talked about this part of what enabling characteristics were in the Hanahan and Weinberg model. And these are, for example, things like defects in the DNA repair system. So these are mutations or other defects in ATM, BRCA1, BRCA2 as an example. And really, they're just trying to make the DNA repair process or DNA damage fixing inefficient. And that means more and more mutations accumulate, which means you're effectively promoting more potential for the tumor to evolve past any therapies, for example, or to evolve new mutation that gives it a survival advantage. What's interesting is that we can actually use some of this to our advantage. So where there's BRCA1 or BRCA2 mutations, what's interesting is you can use drugs called PARP inhibitors in a concept called synthetic lethality. What it means is that usually PARP inhibitors wouldn't be lethal to all cells. They're just by themselves, not a problem. But where BRCA1 and BRCA2 are not working properly, actually... Using the PARP inhibitor means you can't use normal other compensation pathways and there's too much DNA damage and the cell dies anyway. So effectively, we can use it in specific germline BRCA mutations that people have hereditary mutations. But also, we're now coming to using those where people just have tumours that generally exhibit this defect in the pathway called... HRD, that's homologous repair deficiency. So we can test things like ovarian cancers, for example, for HRD. And if they're defective, we can potentially use a PARP inhibitor in those situations to effectively synergize with the defect they already have to then promote lethality. So that's what PARP inhibitors are used for, really. They're usually used in BRCA1, BRCA2. In breast cancers, they will also be used in other tumours that exhibit things like defects in this pathway of homologous recombination, which tries to fix those double-stranded DNA breaks that we talked about. So effectively, what we're trying to do is to try and find a vulnerability in the tumour and exploit it with a targeted drug here. Another enabling characteristic here, tumour-promoting inflammation, we talked about the importance of those stromal cells. Either fibroblasts or macrophages, for example, they can all be co-opted by the tumour to become more tumour promoting. So, for example, what we are looking at is macrophages can have two different types in the tumour. TAMs are tumour associated macrophages and they can be M1, which is effectively your normal macrophages, which will try and kill bacteria. will promote inflammation, will generally be immunostimulatory and have antitumoral activity. Or you can actually get the tumour cells converting the nearby macrophages into M2 phenotype and actually they are immunosuppressive and they have a pro-tumoral activity from that perspective. They're marked by different molecules that they secrete and also different markers, which is how we can study them. So, the tumor microenvironment is really, really important because when we get this kind of inflammation, but ineffective targeted immune response, that fosters further spread and metastasis effectively. And here again, we mentioned cancer stem cells, which is this concept that's reasonably recent within cancer biology. Effectively, those cancer stems. cells will then give more rise to more cells affecting more cancer cells and they can also go dormant in the environment but where the environment is inflamed and immunosuppressed it will be effectively pumping out plenty of extra cells and can also recruit different buddies again different stromal cells the connective tissue cells or the bone marrow derived cells to promote further spread so that tumor Inflammation in tumour microenvironment is really, really, really important. So I mentioned cancer stem cells are basically when they divide, they generate more stem cells, which is effective, they renew themselves as well as the cells that they will go off and be normal cancer cells. So there are small subpopulation of cells, but they're really important because they're quite often reasonably resistant to chemotherapy or radiation therapy, and they can lie dormant for many years potentially. play a role in cancer relapse and metastasis. So here's just a quick, again, summary of the hallmarks, just to remind you what we've gone through, hallmarks and enabling characteristics, and not forgetting that tumor microenvironment is being really, really important. And there's some specific targeted agent or conventional therapies or things that might be explored around these hallmarks. And there's a further evolution of hallmarks. In 2022, Weinberg actually published a new paper, which I've included for you, which talks about four more things that we need to think about. And you can see polymorphic microbiomes playing such a crucial role, which is absolutely our field of work. Non-mutational epigenetic reprogramming, again, we know that nutrition is an epigenetic modulator. So that's definitely somewhere for us to work. Phenotypic plasticity is just about the way that cells can change and senescence again there might be some potential work for us to do within that setting. So now again heavy papers just skim through them if you are interested they're entirely optional but I do suggest you familiarize yourself with just the general gist of stuff. What's interesting again you don't need to read the whole quote is the whole point of Hannah Han's Weinbach's paper or the evolution of the six hallmarks into the 10 plus the 11th tumor microenvironment bed is they said actually if we just target one hallmark or one thing, one specific target, it doesn't deliver. We evolve resistance very quickly. Clinical responses are not really very persistent. What we need is to selectively co-target multiple hallmark capabilities, enabling characteristics. So effectively doing this synergistic approach. What's also interesting is in a couple of paragraphs after that, they've also said that it's too toxic to do that with conventional therapies that are currently in existence. So my proposal is, what about using a multi-hallmark, multi-pathway approach by combining the normal conventional therapies, whatever is currently recommended for that individual, with nutrition, lifestyle, supplementation, other integrative modalities that cover. the other hallmarks or enabling characteristics. But also remembering that it's not all about the tumour, it's about the whole human being. Really all of this focus on the tumour can be excessively so to the detriment of the person. So it's really important to consider their clinical background, their specific drivers and shifting the whole person physiology and biochemistry in a specific and a personalised way. rather than building big and big and non-specific protocols, which is one of my very many issues with the whole how to starve cancer approach is effectively is generic everything for everybody. And we know how well that works in vast majority of cases. And actually cancers are so heterogeneous, you know, even a subgroup like triple negative breast cancer will have different drivers, different pathways in one person versus another. And we'll have... different person or characteristics associated with it, maybe someone is hugely inflamed, or someone is horribly metabolically dysregulated, that's going to get needs to be treated differently rather than just chucking the whole cocktail of stuff at them of, I don't know, six off-label drugs and 50 supplements and seeing how they get on when they don't even have enough room for food after they've consumed all of that. So I would just be wary of that. And I'd say to me, the systems approach is about... Making the best of the science, so multi-hallmark, multi-pathway approach, but also always, always putting the whole person in the front and centre. So what we've done, really, we talked about the general theories of cancer. We then went on and dived deeper into the cancer hallmarks. And I have also included some of the other videos, review videos for the hallmarks for you. So you can go through them in more detail because I know it does take a lot of molecular biology. It does take a while to sink in. Don't worry about individual names of molecules. Just get the concepts in your head because that helps you understand how cancer behaves. But now I want to finish up with a quick review of cancer staging and grading, because that's something that's going to be very relevant to you when you get a copy of the oncology letter. And I do encourage you all to get a copy of the oncology letter for each one of your clients, because it will tell you a lot of information. And sometimes the patient may be unaware of it or may not necessarily be interested in that, but that's going to be important for you. So the grade is the level of differentiation of the cancer. It's the actual tumour problem, whereas the stage is the extent of the spread of the cancer within the patient. Those two are used together to really determine how difficult this disease is going to be for the person. So the grading looks at the tissue sample from a biopsy or after an operation where something has been removed, and it will look at it and go, how differentiated are those cells? And by differentiated, that means how... how closely do they resemble normal tissue? If the cancer cells look only about one or two steps away from normal tissue, they're well differentiated, which means that usually it's a slower growing tumour with better behaviour effectively. However, if they are looking really, really far, far away, they're looking barely recognisable as their tissue of origin, that's a high-grade malignancy that's got poor differentiation. These tumours tend to be more aggressive. and tend to proliferate much more quickly. So that's really, really important. And we've got to remember that the grade is about that specific tumor. And sometimes it's even the area of the tumor, for example. And there is no grade without tumor tissue. Staging is different. Remember, staging is about how far has the cancer spread within that person. So it's based on the size of the primary tumor. How big is it? And this is where the TNM. system comes in. So T is for primary tumour. How big is the primary tumour? T1 is small, T4 is very large. Then we talk about the extent of spread to lymph nodes. That's where the M comes in, N for nodes. So N1, not that many nodes, N3, lots and lots of nodes that it's spread to. And then M stands for the presence or absence of the blood-borne metastases. So M. For example, M0 means you don't have a metastatic disease. It's just the tumour as a primary tumour, maybe a few lymph nodes. But M1, or sometimes in some tumours you even go up to M2, it's the presence of metastases which are different. So for example, you could have breasts that's metastasised to liver or bone or brain etc. And staging is usually done by imaging because you can't do it by looking at a tumour sample, you have to have the imaging, you have to usually do something like a CT PET, which will light up the tumour deposits around the body and then you can tell them actually is it just contained in the nose or has it gone somewhere else. So what's really important to understand is that cancer care in the NHS is certainly usually a multi-professional job. Now, we know that the communication between different professions may be suboptimal sometimes, but ultimately, the key decisions within a cancer treatment are made by the MDT multidisciplinary team. So usually, the key professionals in NHS cancer could involve a medical oncologist, or oncologists that prescribe medication, or clinical oncologists. They prescribe cancer treatment, but they will also I look at radiotherapy, for example. So these are clinical oncologists, a surgeon, clinical nurse specialist, other people that are part of the background team. So things like pathology, people who will look at the tumour samples under the microscope and determine things like grade, which receptors are present, what can you target. Radiology, of course, the people who will interpret your various scans for you and will tell you what the staging of the disease is. and other situation-specific professionals, so maybe physiotherapy or occupational therapy, dieticians, specialist teams, you know, lymphedema nurses, stoma care nurses, and psychologists, for example, psycho-oncology, and there are various others, you know, I've just outlined a few here. I also... We just put a really small glossary of cancer therapy terms. There's plenty on the Macmillan website as well if you want to look at it. But these are the things that are really important because it tells you something about treatment. So when you see the word neoadjuvant, what this means is this is the treatment that's given prior to what we call the primary treatment, the main treatment for the tumor, usually surgery. And again, I'll use breast cancer as an example. So usually breast cancer, yes, will be a lumpectomy or mastectomy to control. the tumor locally. So if we give new adjuvant chemotherapy, that's chemotherapy given before surgery. If we give adjuvant chemotherapy, that's after surgery, so after the primary treatment. And that's important because sometimes you will receive a letter and someone will tell you what they've done and they will say they've been given new adjuvant this and this is adjuvant therapy with X, Y and Z. So you know the sequence of events. And again, some patients will be fantastic. Clients will be fantastic at telling you what exactly they've gone through, and some of them can be quite vague about the sequence and what they've been given, etc. So it is really, really important that you have a letter as much as possible. Chemo prevention, we've discussed it before. It's the use of specific medications and high risk groups to try and prevent cancer. And one example that we've talked about was the use of aspirin in Lynch syndrome patients. Curative chemotherapy. is of course the intention to cure and that's really used in early stage cancers. Palliative therapy can be chemotherapy or radiotherapy. It's not really intended for a cure, it's used in metastatic patients, but it's mainly aimed at making the patient more comfortable. So quite often people might be given palliative radiotherapy to a bone metastasis that's causing particular pain. So that can be quite effective, it can cause a pain flare-up unfortunately sometimes, but... might be effective in terms of longer term control here. Metronomic or low dose chemotherapy is really treatment where low doses of anti-cancer drugs are usually given on a continuous regular schedule over a long period of time. Instead of giving high doses IV every three weeks, they're given on continuous or frequent regular schedule. So low dose treatment really. Remission is... I think reasonably obvious, but it's a clinical state where the tumor, the scope of cancer is effectively less than it was in the past. Partial remission is effectively a decrease in disease activity and full or complete remission is when cancer can no longer be detected. And we also talk about complete response from the medical perspective. So you can have radiological complete response where the. cancer is not detected or in any imaging, as well as pathological complete response or PCR. And that means that there is nothing detectable. If I take a sample of tissue, there are no tumour cells that can be detected. And as we know, radiology or imaging can only pick up tumours when they grow to a certain size. They have to be big enough to see on a scan. Whereas pathological complete response means that I've looked at the tissue, there is no cancer cells within that. And obviously, you would normally not look through the whole tissue samples of it. But still, that's that's a pretty good indication of a robust, complete response to treatment. And of course, we also use lines of treatment. So first line, second line, third line. These are effectively just stepwise regimes that people might go through, particularly in case of chemotherapy. So thank you very much for listening. ________________ 1.5 Monthly Q&A So if we're looking at the evidence between dairy and cancer incidence, it's a really, really big question. The fact is that looking at the epidemiological studies, which are the studies that look at exposures like dairy and risk of cancer and there's many problems with these studies. They they have different results for different cancer types. So you might have read a recent something in the media saying a glass of milk reduces the risk of colorectal cancer, whatever it is. It was they were talking about calcium intake. So dairy, for example, might be inversely associated, which means it reduces the risk of certain cancers And then again, unfermented dairy might increase the risk of certain cancers. So certainly for for example, for liver cancers, some of the unfermented dairy types, not all dairy types, might be associated with risk of hepatocellular carcinoma. So it's not a very simple thing. The idea is that if you're looking at dairy like, prostate cancer, for example, had a big link with dairy. Really, dairy should be removed out of prostate cancer patients' diet. So it's not an easy thing to say yes or no. Okay? You need to research a specific counseling. You need to look at what the data says about it, and then you need to decide what how much you trust that data as well because depending on how they've done the study, there's quite a lot of conflicting data. So it's really, really not a simple question to answer. IGF 1 is one of the factors. It's not the only factor. But the problem is with the meat heavy diet, which was what Sally was asking, we can't distinguish how much of it is heme iron, how much of it is IGF 1, how much of it is whatever else. There's no really good way, you know, to do it from an exposure study where we can't dissect it very well mathematically to be able to say it. So we can't say which part of it is according to what, but we do know that red meat increases the risk of certain cancers and processed meat increases the risk of certain cancers. With IGF 1, yes, they do vary between individuals. However, there is a pretty broad IGF 1 reference range, and certainly having IGF 1 above the reference range is considered to be associated with increased risk of cancer. Not again, not all cancers are necessarily IGF-one linked, but it is certainly something that I watch and test for in certain patients who I consider to be at high risk. And actually where the IGF-one levels come into range as well can sometimes be a really great motivating factor for them to see that as well as some of their metabolic parameters, for example, to be able to continue with the recommendations they get given as well. So, just any questions on this part from the IGF one perspective? It's really is not a and and the dairy side, you know, you are going to be spending a lot of time having a look at these things. It's really not a yes, no. It's bad, it's good. There's always shades of gray and there's always shades of evidence from that perspective. So but generally, what I would say is I have not seen a really good study associate fermented dairy and obviously, we would normally recommend organic fermented with increased cancer risk. We normally see that for kind of processed dairy, so to speak, or very, very high fat dairy can be associated with some cancer types. Any Any questions on this before I move on to Brenda's question about the supplement bit? Which cancers you mentioned are related with IGF, that you would check for? So usually, to be honest, from my perspective, some of the gynae cancer hormone responding cancers usually, hormone hormone respond cancers will will be checked. Now again, I will not everybody can afford an IGF on blood test. And is it gonna be the main blood test that they run? Not really. But you also need to look at their metabolic compromise in their diet. So the other thing is if you have somebody who's going to be having a high dairy, possibly high animal product diet, and you might be concerned because they have ovarian cancer or they have, yeah, endometrial cancer, you just want to see what the link is, you might measure the IGF one and use it as a as a motivating factor. For all I have to say, from my perspective for prostate cancer patients, for example, I would just take them off the area. I don't bother measuring the IGF one for for that as a reason. I will just take them off the area. Because the link is reason we storm and actually even the medics have now gotten on to the whole dairy bed. Not everybody, but you actually do hear oncologist discussing the link between there and prostate cancer a lot more now. There used to be no awareness of that sort of thing. So, yeah, on the other one, in terms of supplements, let me just slightly contextualize this bed. During cancer treatment, anti in terms of oxidative treatments like chemotherapy, antioxidant supplements are not allowed. Doesn't mean all supplements are not allowed. We definitely are allowed to supplement patients on treatment. But classical antioxidants tend to be thought of as contraindicated. Now Keith Block, which is one of the oncologists in the US, says they're not. And while I understand his rationale, at the moment, you will find in the UK, if you're trying to support somebody with an antioxidant supplements during chemo or radio, you will get told to stop, and they will be very unhappy with you. So we don't have enough evidence to figure out what's harmful and what's not. Nobody's run a very good trial, genuinely. When I'm looking at the evidence, we still have no clarity on it. So from the point of do no harm, which is you will always find that operate from that principle, do no harm. So the point when you do no harm, if I'm not sure that what I'm gonna be giving it may cause harm or not, I will not give it. So I don't do classical antioxidant, which is ACE, for example. Right? The where CoQ10 is also classified. ALA is there's a pro and con for certain things, but usually it's under doctor's supervision. But generally, I do not do any of those classical antioxidants during chemotherapy or radiotherapy. And that's just to avoid any problems and any conflicts with oncology and because there is no clarity on the evidence. Because for example, there will be people who will say, well, antioxidants will reduce side effects. I'm like, yeah, they might reduce side effects, but do they also reduce antioxidants will reduce side effects. I'm like, yeah, they might reduce side effects, but do they also reduce the effectiveness of treatment? We don't have a clear answer on that. So we avoid it. Now non classical antioxidants, by which I mean, we know curcumin has an antioxidant in action. Right? That's a completely different thing. That's a non classical antioxidant that has some antioxidant properties, but it's not considered to be a vitamin or mineral which which is directly linked. So that you can use and we do use it. And actually, for example, there was a QFOX trial where they added curcumin to 4 FOX chemotherapy and came up with a better outcome because of adding curcumin. There's a trial of using IV curcumin, in some of the advanced breast cancer patients during chemotherapy, they found an improved outcome. So you can use non classical antioxidants with all the interaction checks as you'd normally do and we will go over those, but classical antioxidants are the only thing that we don't give during active chemo or radio. So that doesn't apply, for example, to all cancer treatments. So I'm sorry if I didn't clarify it properly, but it was more oxidative chemotherapies. It might be in the chemo lecture. And then, yeah, of course, beyond the initial treatment, then again, you will just evaluate depending on what, you know, what what they want in terms of maintenance therapy. I'm just checking this. Juicing Yeah. Good question, Adam. There's no evidence on juicing being being harmful. I'm thinking more about, you know, it's it's quite hard to get vitamin c at 1,000 milligrams into a food, frankly, so we we're just not gonna see doses like this usually in a dietary way. So I don't include juicing within that bed because there's no evidence on that. So for me, food based antioxidants is fine from that perspective. I am going to recommend an high anti antioxidant anti inflammatory diet and high phytonutrient diet to my patients. That's normal for me to recommend it because it's been associated with good outcomes. So if you look at anti inflammatory diets or, you know, diets that measure the energy adjusted DII, which is dietary inflammatory index, Pretty much for most studies, they will show they have a better outcome. So food is fine. It's more when we start people go, oh, I want to supplement 1,000 milligrams of vitamin c during chemo. Then I will say, you know what? Out of proportion, I will not because we don't know if and by how much it might knock off your, oxidative steamer therapy, for example. Let me just check. I've got one sec because I can't always see comments if I'm in in that mode. Will you say a no to glutathione? Definitely not, Heather. So yes, absolutely. It's a very good question. And so I do not use glutathione during chemo and I don't give a urine radium. That's because there is there is evidence, not mechanistic evidence, not not brilliant trial evidence, but mechanistic evidence that it can chemo protect the cancer cell to the same extent they can protect the normal cell. So for that reason, because it's quite indiscriminate in chemo protection, we do not give glutathione during active cancer treatment. I know there are some people who do, and there are some people who really try and give it to the IVC, which makes no sense whatsoever, and I'll type and explain why. But, generally, we don't we don't use the the glutathione during treatment. And to be honest, I'm ultra cautious. I won't use it even in remission. You know why? Because actually, I don't know what's going in there. And I don't know what kind of circulating tumor cells somebody might have, and I don't need it, which is very important. I do not need it because we have things like sulforaphane. Right? We've got sulforaphane, which cannot regulate in a nice physiological way, GST enzymes, glutathione s transpirase enzymes. It's also enough to activate in a master antioxidant. So I just don't I don't need it. And so for a faint, interestingly enough, doesn't have the same problem as glutathione. So so for a faint encounter cells as pro oxidant and in normal cells is antioxidant. It's got a biphasic effect depending on what context you put it into. And therefore, to me, it is a much safer thing. There's no mechanistic studies I'm aware of that shows it's gonna be harmful. So that's what I'm gonna work for. Yeah. No. CoQ10 is a classical antioxidant to avoid during during oxidative treatment. So think about this chemo and radio oxidative treatment. So immunotherapy is fine. Right? It's not an oxidative treatment, so that's okay. And NAC, I I also tend to avoid from that perspective. So I just I tend to use if you have to use something that you think, you know what? I just want to upgrade the GSD enzymes a bit. Maybe there's a little bit of mild hepatotoxicity. Maybe ALT is slightly elevated, etcetera. Sulforophane does a fabulous job. And talking about the person who grows microgreens, you know, broccoli sprouts, freeze dried broccoli sprouts, 1 to 2 tablespoons a day is a wonderful dietary source of sulforaphane that people can carry on for a really, really long time. And, you will see research on sulforaphane and mild elevations and, liver enzymes reducing that as well. Sorry, Nava, did you go? Hi. Can you give a sulforaphane for preventative reasons or is that not advised? I I give it dietarily. Seriously. So I I I very rarely supplement with with with supplements mainly because from my perspective, prevention is actually very important with the broccoli sprout side of things. So a number of my with my patients in the women's health side have a lot of snips in their GST pathways. So their GST p one might be wonky. Their GST on one might be deleted. Okay? So I have to try and make sure that as much as possible support the gene expression of the remaining GST enzymes, and that's what sulforaphane does very, very well, actually. So food. Yeah. Do it through food. 1 to 2 tablespoons of broccoli sprouts on your lunch daily. Just get into the habit of it and just continue. And actually, that's something we can manage. Right? Supplements, we come off and on or, and they're expensive. And actually buy a gigantic bag of, like, sky sprouts, freeze dried stuff, it will last you for ages, it can travel with you and that's what a lot of post breast cancer patients that I know have snips around their pathway or maybe had fat toxicity from chemo, they will be doing that daily because that's something we can do from a food perspective. We should be doing food first whenever possible. And you can buy them frozen. Is that what you've just So they're freeze dried, so they're dried. And if you go into Sky Sprouts, so they're my favorite people, so they're gonna be sold out a little bit probably. Yep. Now I go to it, I don't mind. But go into Sky Sprouts website and you can find freeze dried broccoli sprouts. So basically dried, they're very easy to sprinkle into foods. They're quite neutral in flavor. Again, they're not overly if people really don't like over broccoli flavor, they're much more neutral from that perspective. But that is what I tend to use. And so for a thing, yes, I can supplement it, but I always start going with food. And then when I don't get enough effect, then I might do supplementation. Yeah. Broccoli seeds, it's definitely a very easy to spread yourself. Gabrielle, I would love to do that, but frankly, you know, I'm pretty sure we'll go moldy because Machedra won't allow it. So I decided to go just with freeze dried for use, but yes, you can sprout them yourself, absolutely. But broccoli sprouts are fantastic and a brilliant source of sulforaphane and of course, lots and lots of other things apart from sulforaphane because they are whole food matrix. I take it then you don't ever recommend DIM, not that I would because I'm I'm going to have a great agreement, I think. Yeah. You're not you're not allowed to recommend them from the NT perspective. The other reason I don't like to recommend them is actually in people who have sip 1b1 snips. DIM can actually upregulate for hydroxy, estrogen metabolites. So the harmful metabolites, the ones that form quinos and can cause DNA damage. So until I know the genotype, I wouldn't touch them. Again, I've never needed them. Like, I just don't don't put in my practice because there's no much point in it from my side of things. I've got other tools. I've got so many other tools, that I just don't need it really. So is not classical antioxidant. Again, you would need to check interactions. And if it's fine, then you can potentially use it. So resveratrol is one of those non classical antioxidants taken in this region. And thank you, Becky, for the end of 1. So well well done. That's brilliant news. Dehydration, yes. I'm pretty sure you can dehydrate them, just as long as you use it safely. And classic answer for your multi. I don't do, classical antioxidants from a multi because you're gonna number 1. So let's just think about the practicalities of it. Technically speaking, if you wanted to, you could go to 2 half lives of chemotherapy and then try and give an antioxidant. Right? Not one half life. One half life is only half the genome. 2 half lives. Okay? But you're gonna still get into an argument with the oncology pharmacist or oncologist because you're giving classical answers. It's doing chemotherapy. Don't forget, it's not just about the chemotherapy effect. The chemotherapy might be out in the system if the effect of the chemotherapy on the body continues for days afterwards. So just using half life is actually not enough. And I just tend to go for the safest option. So you will find, on the side of caution, you can choose not to, but I want you to understand why I do in terms of rationale in that perspective. So, dim, you can if you want to consider it after treatment. From my perspective, just be cautious of the patients with estrogen dependent cancers who have sip1b1 because for some of them, they will upregulate their 4 hydroxyestrogen metabolites, and they will get more quinones and more DNA damage. So just try and be a little bit more more sensible about it. And, yes, broccoli sprouts from Abel Hall is lovely. It's it's delicious. They're really, really good. So, fab, everybody's gonna have a lovely broccoli sprout after this. I I feel it's coming on. Good. Then the other ones, diet and cancer, diseases are important things like methodology. It's tricky. Their epidemiological studies are notoriously difficult to conduct. There are many long term studies and many cohorts have gone to decades. They're very expensive, these studies to run. Can you imagine trying to follow-up thousands and thousands of participants? It's a lot of money. But, they are self reported. So there are some studies, however, that do use biomarkers of intake. So in a few studies, you will find they might have used carotenoids as as a surrogate marker for some of the fruit and veg intakes. So are they ideal? No. Which is why you always have to take them with a pinch of salt. Like egg studies, I take with a gigantic pinch of salt. You know why? Because how do most people in a standard British diet consume eggs? Tell me. What do they normally do? Go on. Fried. Fried. Yes. Fried and in a very popular breakfast called the breakfast, they basically put a load of with it. I'm really sorry to say that, but it's free. Right? So they're not gonna be making a lovely shakshuka with full of lycopene and antioxidants and fresh herbs sprinkled on top. Think about who these studies are done by. They're done on the average individual who is probably eating eggs, like you said, fried in a mcmuffin, you know, whatever they're doing. So trying to do egg studies is very difficult. They said the effect of actual egg versus the highly processed red meat that normally would have the eggs with red meat. Think about it. How many people do you see that will have eggs with red meat, like bacon or something else? So and a lot of people will maybe overeat eggs as a part of that very, very high animal protein, high safflower diet. So it's really difficult to try and say it's the eggs that did it. And a lot of the time in those epidemiological studies that don't adjust for what we call confounders. They're the things that are associated with egg intake that are causing the problem, but we don't see it because they're behind it. So they don't adjust properly for it. They're very, very difficult studies in general to run. In terms of red meat and cancer, it's not just processed meat because heme iron does does, make what we call nitroso compounds in the gut. Okay? So processed meat has extra nitroso compounds and the red meat nitrosa compounds that can damage DNA. Okay? So processed meat is a double whammy. Red meat is still a whammy, particularly if you've got significant dysbiosis. Guess what all of our patients will have? Significant dysbiosis. It doesn't mean no red meat, but the caution there around mounds is applied from former epidemiological studies basically. So that's where it comes from. I'll just quickly show you. If you want to look at some of the evidence, I would suggest going into the World Cancer Research Fund report and just seeing some of their references as well. So none of this is ideal. I mean, epidemiological studies, you can do it this way. So this was what they have, for example, on their page. They have a massive professional report with reference thing, by the way, and they they explained some of the really common mechanism. So, obviously, now the triple whammy is if you've got a red meat and then now you're gonna barbecue it and you're gonna form not only nitrosy compounds, but heterocyclic amines and polycyclic aromatic hydrocarbons, and then you've got further risk of colorectal cancer, etcetera, etcetera. But you can you can have a look at it. There's many different there's like a 300 page report. You also can go and look at different cancer types. So you will see there's a number of different things within that bed. There's lots of research and policy bits and pieces. Like, for example, interactive cancer matrix will have different cancer types and different, you can see, lifestyle components. So you can have a look at it. You can look at it at which one is the strongest evidence matrix, for example. So that's from the report. You can look across cancer types and what they found. So that's quite a useful way of doing that. So that hopefully answers the red meat question. Let me just find this back onto our page. And then microplastics, one of the things so Daisy was asking about microplastics in fish. So just so you know, there's no data on microplastics in fish and estrogen related cancers. I can tell you microplastics are unfortunately everywhere. In they they they did a study where they took fish, meat, and a number of sources of protein from the supermarket and tested them for microplastics. Every single one had an appreciable amount of microplastics in it. So, unfortunately, it's not just fish. So that's just something to be aware of. People get very, very focused on the ocean pollution, which is definitely a problem, but it actually comes across all the different sources of protein from that perspective. And then, Daisy, I'm gonna ask you this question about the one center's description at the end of the course, and then we could all see if we can come up on. Because I want to do I want you guys to do it. I think it is really important that you all come up with one sentence because what we do is very, very different. You know, people so many people contact the clinic saying, can I have the metabolic protocol? Can I have the off label drugs or whatever it is? I'm like, I just don't do protocols. There's a reason for why I don't is because we do ultra personalized medicine. Good. Any questions on this part before I move on to Gabrielle's questions? Okay. Good stuff. Does chemotherapy damage the immune system gut microbiome? Yes. You will learn all about it in, month 3. So when we cover the GI side of things, definitely, it does damage both and then we do need to do a lot of rehab really afterwards to be able to do it. S v 40, simian virus, 40 in many cancers. So that was the concern with the old polio vaccine in particular. So about 1955 to 1963, we had SV 40 in our polio vaccine, and as soon as death contamination was found, then it was stopped. So unless you work with monkeys and are exposed to SV 40, you do not have any SV 40 in any of our current vaccines. So that's a historical concern. Did it contribute to cancer? Possibly because there is evidence that it is carcinogenic in humans, but interestingly enough, not this original post for monkey. So yeah, that's kind of a historical thing more than anything else. Histo tripsi, histo tripsi has been approved by the FDA, that's true for a small number of indications. So, histotripsy is using, yeah, sounds and water, basically blasting cancers locally. It's a subtype of what we call ablation, so that means using a technology to destroy a tumor within this local environment. So we have 2 trials running on this, I think, in the UK that I'm aware of. So there's 1 in liver cancer, 1 in kidney cancer. It's really important to realize though that anything to do with ablation can only treat local. If you've got disseminated cancer, it's only gonna treat the lesion you can treat it. Okay? It's not going to actually unless you have contained primary cancer that they can access, it's not gonna treat the rest of the cancer. So ablation methods are useful for gaining what we call local control but they're not systemic treatments. And then oncolytic viruses, there's there's several viruses already approved, an eye in clinic for oncolytic biotherapy, and there's many more in the pipeline. The problem with oncolysis viruses, a lot of the time when we use a virus I don't forget how immune systems are really good at eliminating viruses. Okay? So part of our problems with biotherapy is that we need to somehow get the virus that carries the therapy to stick around in our bodies long enough to not get eliminated by our own immune system to deliver the treatment. So there's a lot of research work that's going on with that, but it is already in clinic. So it is being used in it's been used in, for example, some of the malignant melanoma cases as well. Any questions on those 4 at all? Any other comments or thoughts? No? All we're okay? Glutamine. That's an interesting one. So glutamine should be avoided with that. Yeah. So I I'm I avoid glutamine, okay, from my perspective. Again, we're gonna get into the reason reasons and rationales. So I would glute to me for the fact that we don't have any good long term studies on how it affects cancer outcomes. So does it improve mucositis? Yes, it does. Yes, it does. There's very good evidence they improve mucositis. Can I improve mucositis in another way? Yes. I can. And therefore, do I need to use glutamine when I'm not I'm not certain about long term outcomes? I don't. So that's why I don't tend to use glutamine. I know Keith's Block Keith's Block actually uses both antioxidants and glutamine, but, again, where is my long term data? I want to see that if I'm gonna use something that helps the short term side effect, I'm not gonna shoot myself or my patient in the foot a year down the line when they've gone through treatment hasn't worked as well as possible. So because glutamine can be subverted into making fuel from the cancer cell perspective, and there are certain cancers that particularly love glutamine, I don't don't use it. In Australia, it's used really commonly, again, because of the mucositis side of things. I think the only time I tend to use glutamine is really in the palliative setting when I really need it for whatever reason. We're not getting on top of mucositis control. And at that point, we are really, really down the road with palliative intervention. So I don't tend to use it very much. So, yeah, that's just my rationale. But, yeah, you will find all sorts of interesting protocols out there on that side of things. And then your cooking, sorry, I'll go back to broccoli sprouts. Yeah. I agree with you. There's no good studies on it again, but from what I understand, I tend to eat them raw freeze dried because that's what the studies have shown has a good effect on absorbency of morphine. So probiotics during chemotherapy and avoid probiotics when you immunocompromised. So probiotics have been studied during chemotherapy. Okay? That's an important note. Now I tend to avoid them when people are significantly immunocompromised, which means their neutrophils are below 1.2. That's what we tend to use as a practical cutoff. Okay? And it's a clinical cutoff because usually when you need to say below 1.2, there's a significant amount of antibacterial immunity that is lost. So it doesn't mean you can't use probiotics ever with patients, but you do have to be cautious of those that are really profound in neutropenic. They did find that with probiotics being given to patients who are on ICU, unsurprisingly, with horrible intestinal permeability, give them a probiotic and ends up in their bloodstream. Well, you didn't need to run that study. We could have told you that. Right? You're not gonna give a probiotic patient to an ICU to an ICU patient. You're not gonna do that. It's just not gonna happen. But they will find it. So people who are profoundly neutropenic or obviously in really profoundly horrible states like they are in ICU or HDU, we wouldn't get probiotics too. But outside of that, your normal ambulatory running around patient get coming in and out of chemotherapy cycles at neutrophils above 1.2, we can't give probiotics to. And I do sometimes. Sometimes they need it for various reasons. Legumes because of lectins. Oh, god. The whole lectins debate is Show me a single study that shows that legumes, increase the risk of cancer. Can anybody show me one? Anybody? Anybody? No. You know what? There isn't one. Not as far as I'm aware. So if you do a good search on PubMed, you're probably not gonna find one. So, Adam, as much as I love Naysha, for many reasons, I would say NACE is very heavily invested in the ketogenic diet, and you will get that angle. So be aware of the bias of whoever's telling the things. So I I agree with you. I just don't think there's any evidence of that being harmful. So we do use. The only thing you have to be cautious if there's a very specific things about new stomas or other bits and pieces around, GI compromise. It's really significant. Estrachate properties of legumes. So oh, well, let's answer that question, Rashid. Come on. Let's do it together. That will be quite fun to do. I like, I like plenty answers to questions. So let's do this. Let's find out legumes and the risk of breast cancer. Let's do a little search and see what we find. So phytoestrogens act on a in a different way, which we'll talk about in a second. Let me do this. Legume and breast cancer. If I really want breast cancer, I'm gonna do this one. So let's just see. Legumes. Legumes. Oh, no. Look at dose responsiveness analysis. That sounds quite fun. Let's do this bit. So what do we have here? So we've got improved risk with vegetables, fruit, cheese. Interesting enough. This one oh, no. This one. The relative risk is one neutral. Soy. Red and processed meat is not good. Where's our legumes? So apart from soy as a legume, we don't see anything here. One sec. I'm just gonna see if I can find a better one that actually has some legumes apart from soy. Oh, there we go. Let's do this one. Let's have a little look at that. One moment. I could tell you that I haven't found, anything on this but, let's do this bit. Legumes, legumes, legumes. Where's my legumes? Oh, here we go. A significant inverse association. That's another one. I mean, this is just a single study. You will find the whole both of those things. So this one, significant association was found between legume intake and breast cancer. People consumed top top turtle of legumes had 46% lower odds of breast cancer compared to bottom turtle. Right? So that's a pretty amazing result if legumes had estrogenic properties that they increase the risk of breast cancer. So do they have fatty estrogens? Yes. Flax has fatty estrogens. Is it bad for you when you have breast cancer? No. Soy is actually soy, normal soy products. So we normally recommend again organic fermented natural soy, not frankensoy. It has been associated with, better outcomes in estrogen receptor positive breast cancer. Okay? So we don't need to be afraid of phytoestrogens. What I tend to do is supplements are different. So if you're trying to do think about soy supplements, we haven't studied pure isolated soy phytase in high doses in women with estrogen receptor positive breast cancer. That's not been done, so we don't supplement. Food wise, you can absolutely use legumes. And you can use miso, and you can use tempeh, you can use tofu. And sexually, looking at meta analysis, it's it's associated with better survival. So I'll show you a meta analysis from one of my colleagues, Channing Parler. Let me just find you a one about breast cancer. You know, I take it this goes for prostate as well. Yeah. I mean, it just it we've kind of gone a little bit mad and it I think it was because of the, yeah, I mean, the whole phytoestrogen debate has been going on for so long. There's actually no real good evidence behind it. And you gotta remember that when we're thinking about phytoestrogens, they preferentially bind to estrogen receptor beta, not alpha. So if you're thinking about we've got 2 main mystery receptors at 2 kinds. Alpha is alpha is gas. Alpha is progrowth. Right? Our own estrogens preferentially bind to ER alpha. Right? Now ER beta is breaks. Right? So, yes, it still binds estrogen, but actually it's antigrowth from that perspective. Now where do phytostrogens preferentially bind? I hear you say beta. Beta. Yeah. Yes. So doesn't mean they won't bind alpha, but preferentially, our own endogenous estrogens will bind alpha. Your soyflax, blah blah, interlocutants, they will bind beta. So we will preferentially be putting more brakes on than the gas. Right? Our our own endogenous estrogens are the other way around, unfortunately. So but this is another example here. So if you just be aware of this study that's done by my colleague, Annipsey, Carrie Bone here. Ta da. So look at this one. For example, if you're looking at soy protein and products were inversely associated with cancer specific mortality for estrogen receptor positive breast cancer, 25% reduction in mortality as breast cancer specific. Right? We can absolutely safely use normal soy products in that perspective. So there's absolutely no problem with doing that. So this is just so you know. Cool. Does that make sense? Is that okay? I keep it pretty clear on that one. So this is this is actually quite good. It's nice nice good great opportunity to discuss these things that float around in the atmosphere still. Do do do. Let's find more. And then, yes, PSA. So I want to just quickly show you the question from Helen so that you guys can read it. So it's a very good long question. The answer is, I think, importantly, is that we don't have a study that personally monitors people's PSA over the next 40 years when they start off young and then their subsequent risk of prostate cancer. We just don't have it. So we don't know whether if we adjusted for the men's young normal, whether we would get better outcome. But PSA is absolutely not the best tool for screening. So we use these days circulating tumor cell based screening methods, you can use EpiSwitch, you can use other things like that. So it doesn't mean I never run a PSA, I do run occasional total and free PSA, do the ratios, but there's now much better testing for prostate cancer screening than pure PSA. And of course, it will rise anyway with age. So that's one of the other issues with PSA testing is do we think it's benign prostatic hypertrophy or do we think it's cancer? And then for those people who are between 4 10 on a PSA, it causes a lot of anxiety, potentially unnecessarily because they've got benign prostatic hypertrophy. Bye, Natasha. So, yeah, PSA not not unfortunately the best. It will be lovely if we had a simple blood test that could differentiate, but it doesn't at the moment. And then truly unpreventable cancers, so that's an interesting one. So just read read that top bullet point so you can go. I that's exactly what I'm I think I said this in the lecture. I said that classical estimates of what percentage of cancers are preventable are underestimating it. I think it's much higher, much much higher. Do you know why? It's because we haven't studied gene environment interactions. So if somebody tells me, I don't know, 30% of prostate cancer is preventable. I go, it's probably like 70% plus actually if you tell me, but we haven't studied it. So they're not very good at actually unpicking those gene environment interactions. So, yes, I think a lot more is preventable than a classical medical data suggests effectively. But truly unpreventable is there's a very tiny tiny proportion of that is what I would say. And that I mean, things like retinoblastoma, childhood cancers that are due to inborn genetic errors. So if you are a person who is in a retinoblastoma family, you've got a mutation in retinoblastoma 1 gene, which is a high penetrance mutation, you are 90% plus likely to develop retinoblastoma. That is, I'm sorry, whatever you do, that is a fixed genetic mutation with a high penetrance that will result in cancer. Right? So that's what I mean. I don't mean any of our normal ones in terms of breast, prostate, lung, etcetera. You know, I once had somebody with a really young, colorectal cancer whose consultant just told them it's bad luck. And I'm like, number 1, they didn't even bother testing her genetics. But even if they did test her genetics, the first thing they failed to ask is actually what was she eating at all? And this lady was, you know, microbials since childhood because mother couldn't cook. She didn't cook at all at that point when I've met her with her colorectal cancer diagnosis and her consultant had no idea how much fibre she was consuming, what else she was eating, etcetera. So I'm like, before you conclude with bad luck, why don't you actually try and find out what other risk factors that might be present in somebody and how you can counsel them against there is maybe bad luck, but until you've actually looked at it, you can't really say that. NHS, prostate cancer screening program, they they are not going to introduce that with the current testing, Rashim, and that's because it's so poor at differentiating between prostate cancer and not. So maybe if secondary tumor cell testing gets licensed for screening, but it's very expensive per person, it's very unlikely to be to be done. EPIS which again is about £900 per person. Exactly. So think about the NHS investing in this, it's not gonna happen. So until the cost of some of those newer much better screening test becomes something like £20, it's very unlikely we're gonna have a full on prostate cancer screening program at the moment. So it's just something to to bear in mind. So, yes, at the moment, I don't think they have any plans because the tests are not good. Then the other one was about lactate. So that was a good one. So would lactate be any use in terms of flagging for cancer? No, not really because lactate will get metabolized. You will metabolize your lactate really quickly. Now LDH can be occasionally used in some cancers as a marker, but again, I wouldn't use anything as a single marker for all cancers. It's just it's just nothing like that at the moment. Cervical cancers and at home testing, there's certainly I think, yes. There's a lot of tests out there at the moment. Just make sure that they're properly licensed. So if we're doing an HPV test at home from a swab, in terms of instead of entering a cervical screening program, then need to make sure this analyzed in a properly medically accredited laboratory. So usually they need to have something called UCAS accreditation. So they need to be able to be run properly. Otherwise, I can make a case in my basement and say, look, it detects high risk HPV, you have a swab. So as long as it's well regulated, the HPV triage tests are done at home can be really reliable and there's a few on the market from that perspective, but you just need to look at it and see that it's done via via a properly accredited company effectively. Microbuying, how much, how validated? I do have a single really well validated test for the cervical microbiome from these tests. So HPV triage is very different. So from the HPV perspective, knowing that you have high risk HPV should push you down further investigations pathway. Do you have any dysplasia? Do you have any initial changes in the cervix? Now nobody has so far created a really good cervical microbiome profile that's predictive of dysplasia risk in women. So until we have that and until I can tell you, I can not only do a swab and not just give you markers of interest, but I can tell you you have a 15% chance, increased risk of cervical cancer, get yourself checked. Until that happens, that's not test I would be using from that perspective. So I do do testing of, you know, vaginal microbiomes and other things, but not with the view of counseling people against their cancer risk or with the view of optimizing the health from that perspective. We don't have good data on that at the moment. It will come. I can guarantee you there will be something in terms of medical development in the next 5 years that will look at the snapshots of combined microbiome, maybe some of the metabolites, and they will come up with really good predictive models, but not just yet as far as I'm aware. Unless somebody is aware of a test that I haven't seen, which, you know, you might be because there's lots and lots of tests out there. MDTs. So, yeah, so Becky was saying, look, MDTs can delay delay people's treatments because you have to wait for the MDT to make a decision and then, you know, potentially if you had your scan and then there's MDT and then it doesn't meet, it could be 2 weeks before you get a treatment decision. So and will that change with West treating being empowered? MDTs will not change. They are highly unlikely to change for the reason that they're meant to be actually a safety mechanism for patients. So a lot of the problems can come if a single medical professional makes all the decisions on a cancer case because they can be biased, they can be blinded, they might not know about all the treatment options available. So MDT is a design that a team of medical professionals sit down and actually look through the case and look at all the different options for treatment. So for some of my patients, might be we might need a a radiation oncologist in there. We might need a medical oncologist in there. We might need a surgeon in there. We might need pathologists in there. We might need radiologists in there. So we can see everything. We can decide is is it surgery now? Is it chemo now? Is it targeted therapy now? What what is next? So there's a lot that happens in the NDT that it needs needs to continue happening. Whether they can speed them up, I don't think so either. Realistically, we've got big patient list to get through in the NHS and I don't think it's gonna run any more than once a week. Does it introduce delays? Yes, it does. Is it the only factor in NHS delays? No, it's not because we've got massive problems in accessing treatment in terms of waiting lists for for multiple other reasons. So that's my my quick answer to the MDT question, which I hope is okay. And then Please go. Yeah. I was just gonna say just a context. So I'm a personally big fan of the MDT having benefited from it and had some really good conversations with the clinicians. And also they I'm really lucky in my hospital is that they would tell me what happened in the MDT. If there was disagreement, they would say, like, oh, well, 50% of us thought you should do this, and 50% of us think this. And because I did the dilemma. So it was really it was a really excellent process as they fully involved me. But I so I've got this mixed mindset because the the delays in the MDT can be an issue. So if you're trying to wait for your results, you know, 2 weeks, and it's mentally very stressful for the the cancer patient. But on the other hand, a little bit of delay could be enough benefits in nutritional therapists because we get to do interventions. So if I didn't have a delay, Linda and I wouldn't have been able to work on my gut microbiome to get ready for my chemotherapy treatment. So, actually, some of that delay was really beneficial. So I kind of have a mixed mind with it. Yep. And I think from my perspective, you know, if we think on on your side, I think it's important that you do whatever is within your power to optimize the person in front of you. And like you said, sometimes prehub can be done, sometimes other things can be done. We the whole the other thing is you will come across these watch and wait periods in your in your client's treatments. Right? Watch and wait is a sitting duck if you don't do anything. Right? That is what you are doing. You are sitting duck. If you are actually working in nutrition lifestyle, psychological, emotional well-being, and other things like that, you're not just sitting down. That is not watching wave. That's active intervention that's supportive for the person. So you have that power within those watch and wait limbo periods, etcetera, etcetera to actually start doing positive changes and give the agency back to the person rather than feeling like you're out of control and limbo going, no. There's actually a boatload of stuff that I can do to make myself better. I can optimize my vitamin d. I can do this. I can make sure, but my cardiovascular fitness is great. Bye, Tanya. We're gonna be finishing anyway. But, yeah. So I completely agree with you, Becky. I think there's a double edged sword. I think if realistically, as a medic, what I would say from my perspective, if I'm desperate to get somebody treated and I don't want to wait, I won't just make an we can make an entity happen. You can I can make sure you're breaking around the oncology team and say, right, this person needs to be in treatment this week? And that's the power that I will have as a medic is to bring the team together and say you need to have an emergency meeting because they need to be in treatment this week, not next week, not in 2 weeks time, etcetera, etcetera. But those cases, I would say, are very few and far between and are probably decompensating metastatic cases. That's really where I actually need to get on the phone and say you need to start chemo now, which is yeah. That's that's tricky. So I'm with you on the MDT power, but your MDT sounds amazing and I want to know where you went because this is We're amazing. I'll tell you more about it. Perfect. So what I'll do is I might, because we've run out of time, because that's so really good questions. I will hold off and I will answer the rest of the questions separately. You now know where to find the evidence from the WCRF report. Just go on the website, find report, download it, search within it. You should be able to find all the original references for everything. And, yes, treat with some suspicion. But the other things I want to say is, I want to ask one question before we stop, and what do you think has led to a decline in stomach cancer cases over the last, say, you know, 20 years? Any ideas? Just give me an idea. More more cases found of h pylori and the treatment of h pylori? Yes. The reason that guy drank the h pylori cocktail and gave himself an ulcer. Absolutely. So yes. I understand. This is why the researcher wasn't believed. You know, we knew about h pylori in stomach cancer since, like, the sixties. Right? Everybody believed and they were like, no. Come on. No. It's a bacterial cause for stomach cancer. So in the end, the researcher had to actually drink h pylori and give himself a stomach ulcer to prove that actually this is what's going to happen. So, yes, absolutely. It's a treatment of H. Pylori that's transformed the stomach cancer side of things. And the only place where it's not been as apparent is probably in Far East where they eat a lot of really highly preserved foods. Some of those populations that actually they still have a much higher stomach cancer risk than some of the other populations. And that's mainly because they eat a lot of these really, really strongly preserved foods. They've got a lot of salt sometimes as well. Exactly. So that salt basically is salt pickle type things and it would normally have preserved meat and preserved fish and a number of things. So because of that kind of highly processed, highly salted preserved product in some of the far eastern company countries you get from DC are still higher risk of stomach and esophageal cancer. And and smoked fish as well, apparently. Yeah. Yeah. Exactly. So all of those yeah. Yeah. I mean and smoked fish, I mean, you have to eat in high amounts, but there are certain cultures that we know will eat them in really significant quantities. Yeah. Definitely. So, unfortunately, that is true. Can I ask one last question just in the context of that? What would you say is the gold standard test for h pylori? Oh, so many arguments about this. So it depends on what you're trying to do is my answer. Okay. So if you're trying to get your patient treated on the NHS, you have to do stool antigen. Right? Without a stool antigen, no but not a single sausages are usually gonna treat you. And, normally, if you send them in with a different test, they will still bind the stool antigen to confirm what you're doing. K? So, like, is stool antigen the best test for hBolore? Maybe it's not. However, that's what they use in NHS as a guideline. Now if I am doing it because I want to treat H. Bylori, I'm quite happy going with a PCR that's done in the UCaaS accredited or CQC registered laboratory. That bit is important because not all labs are created equal. So we sometimes been possibly slightly tricky. The numbers on the sheet are real. Right? They all have an error margin and there's false positive and false negative. So PCR is not perfect, neither is dual antigen. They all have numbers of sensitivity and specificity, which tells you how good the test is. So if you're gonna trust the result, just make sure it comes from a lab you trust from that perspective. So not all labs, unfortunately, certainly functional labs, you not all labs you can trust for an h pylori result. But if you want to treat it on the NHS and you've fallen around to a GP or oncologist, you have to restore antigen. Unfortunately, that's just the way it is at the moment ________________ 2.1 Overview Of Cancer Treatment approach to cancer program for nutrition professionals and today we'll be talking about the medical treatment of cancer as a part of your module two lectures. So let's talk a little bit about the different treatment options in oncology and they will include a whole range of different treatments including surgery, chemotherapy, radiotherapy, hormone therapy or we would normally say endocrine therapy. targeted therapies that are effectively targeted against a specific drug target, which is for example anti-HER2 drugs or what we call tyrosine kinase inhibitors, as well as immunotherapy. And there are some very specific treatments that we could use, for example bone marrow transplants that we can use for blood cancers. We'll talk through them in very general detail, you don't need to know a whole ton about this. You can kind of go as deep as you like within that, but I will cover broad strokes that you will need for your work as a nutritional therapist. So in terms of cancer therapy terms, you need to know some crucial terms within that setting. If something is called neoadjuvant and you will see it with a dash or without a dash, that's usually chemotherapy or different treatment given before the primary or definitive treatment, usually surgery. So if you've had chemotherapy, then surgery, and then another lot of chemotherapy, you would have had neoadjuvant chemotherapy, then surgery, then adjuvant chemotherapy, which is a therapy given after primary treatment. So effectively, quite often, depending on the cancer type, things are relating to surgery within that setting. So before is neo and after is adjuvant. Chemoprevention is a use of specific medications, high risk groups to prevent. cancer or really to minimise the risk of cancer. Curative chemotherapy kind of does what it says on the tin. It's intended to cure or cause significant progress in terms of treatment of cancer and that's usually what's employed in early stage disease of course. Palliative therapy can involve chemotherapy or radiotherapy. It is not intended to cure a disease or necessarily cause remission but it's mainly aimed at making the patient more comfortable and potentially extending their life as well. Maintenance chemotherapy is a low-intensity course of chemo, usually given after a treatment course, and it doesn't have to be chemotherapy. It can also be treatment with targeted drugs. So, for example, for ovarian cancer, it would be things like PARP inhibitors and Avastin being given as maintenance therapy after someone's completed their surgery in chemotherapy. In metronomic or low-dose chemo would be... exactly what it does on the tin. It's a regular schedule of continuous or frequent low dose of cancer drugs instead of giving them in cycles like doing an infusion once every two to three weeks. Remission is a clinical state where we know that the scope of the cancer is less than it was in the past and it can be partial or complete. So partial remission is reduction in disease and full or complete remission is when the cancer can no longer be detected. And we also sometimes talk about a treatment response and it could be a clinical response, so it could be a radiological response or pathological response. So it's different ways of measuring responses depending on what kind of thing you look at. So if you look under a microscope at a person's tissue and you can't detect any cancer, it would usually be called complete pathological remission. And if you look at their scans and you can't detect any cancer, it would be called usually complete radiological response. Or the other ways of talking about is NED, no evidence of disease. So these are just some terms to be aware of. And, you know, you pick them up. Don't worry about learning them all at once. You pick them up as you go along. And in terms of different treatments in the order that they're given, they're called first line, second line, third line, etc. So staging of cancers. It's really important to know how we stage cancers. Most of us have heard of stage 4 cancer, now it's metastatic disease, but obviously there are other stages involved. And we stage based on imaging usually, okay? So it is based on the size of the primary tumour and how much it's spread to the original lymph nodes and whether we have metastasis to a distal side, so somewhere else in the body apart from the primary tumour. And the major staging system is a TNM system. So we use it for most cancers, certainly solid tumours. We use T for the size of the primary tumour, so the bigger the tumour, the bigger the T number, ranging from T1 to T4. N is used to indicate regional involvement, so N0, no nodes involved, and 1 to N3, increasing numbers and ranges of nodes involved. And M is for metastases, and that's M0 means we can't see any distal cancer spread, or M1 and sometimes even M2 means that there are metastases. And as I mentioned, staging is done by imaging. It can be a CT scan, it could be a CT PET scan using radiation exposure to establish where the tumour has spread to. So we're now going to go into the different treatments and I'm going to give you a very broad brushstrokes of treatments. So remember, this is not meant to be exhaustive, but it's meant to give you some ideas about what people with a cancer diagnosis might be going through. So surgery, there can be three aims for surgery in cancer. You could use surgery to biopsy a lump effectively to make sure that it is or isn't cancer. You might use it for surgical excision, so to cut out a tumour to try and be able to cure cancer really. And that's usually used in early or localised cases. Or you can also do an excision even if it's not a curative intent but really just to try and reduce the burden of disease and that's called debulking sometimes so when we debulk a disease we're not aiming to cure it just with surgery or even low-grade intervention we're just trying to reduce the disease burden and usually this is followed by chemotherapy afterwards and can be quite extensive so For example, in ovarian cancer we quite often use debulking surgery before we give further chemotherapy in case of extensive disease. And surgery can also be used for palliation, so that means that if someone we're not aiming to cure or even treat the disease specifically, but we're aiming to relieve symptoms and that's things like where the tumour is compressing the spinal cord and so we need to relieve that compression or things like stomas where we What we call defunction in the bowel, so where the cancer is actually obstructing the bowel, we need to effectively defunction or stop that area of bowel from working because it's causing problems. So the area of the intestine before that obstruction can be brought out into the skin to form a stoma. And the bowel later on effectively is now no longer functional because the stool is going through the stoma. And that's called a defunctioning stoma. And again, you don't need to know everything about it, it's just to give you an idea of how surgery can be used in different settings in cancer treatment. There are various complications of surgery, I'm not going to read through them, you can look at them together. The immediate ones are really obvious, bleeding and shock during surgery. The early ones tend to take place within really a few hours to a few days. following surgery so that's anything from pain and confusion to nausea and vomiting to secondary haemorrhage or infection and a number of other things and bowel obstruction due to adhesions can be either early or also later complication as well. So late obstruction late complication include the obstructions I mentioned there can be other problems such as hernias at the site of the surgery So where there's already a defect, it's easy for things to poke through. There can be a recurrence or keloid formation, which is a really big, extensive scar that's quite bumpy. And obviously problems with cosmetic appearance, etc. And there are other things that are specific to different surgeries. So, for example, where you have breast cancer surgery and you've removed a number of lymph nodes, lymphedema or accumulation of lymph. in that limb is going to be a problem and it's also a problem if you remove things like inguinal nodes so groin nodes in some of the pelvic surgeries as well. So it's just important to be aware of the fact that surgeries can get complicated, a number of things can happen. Moving on from surgery to chemotherapy, so chemotherapy are really cytotoxic drugs so drugs aimed to kill cancer cells that are given by injection or orally usually. The whole point is to disrupt the replication process of the cell to cause enough damage to promote cell death. And because chemotherapy usually is targeted at rapidly dividing cells, because we're trying to affect the growth process, that usually means that it can affect other normal, rapidly growing tissues. That's, for example, things like the bone marrow. which is why we have problems with cell counts or white cell counts for example during chemotherapy as well as the bowel because as we know the lining of the small intestine for example can get replaced very quickly so people can get a lot of GI side effects as well and of course hair follicles etc. So IV chemotherapy is usually given in cycles and the cycles are given a set number of days. So that means a treatment is given, then the number of days that treatment isn't given, and then you get given the treatment again. So a 14-day cycle means, for example, day one, you're given chemotherapy and then again you go through the rest of the 14-day cycle and then you get given chemotherapy again. So it allows the normal cells and the patient time to recover. Now dose-dense chemotherapy tends to be given more frequently, so really that's usually weekly, for example, so there's different ways of doing that. And there's more information here on that link from Macmillan if you want to explore chemotherapy a little bit more. Okay, so let's get into a bit more about chemotherapy drugs. There are lots and lots of them. So you don't need to know all of them. All you need to know is that the vast majority of them are targeted at the cell cycle and that's cells replicating themselves. There are different classes of those and they all act slightly differently. And based on that, their side effects can be quite different. But again, if you're really, really interested in it, you can read more about it on the Macmillan pages. most chemotherapy is targeted at different points in the cell cycle where the cell replicates and divides because we're aiming to target rapidly dividing cells, which most of them are cancer cells. But of course, that's why we have bystander effects on normal tissue. So radiotherapy really aims to use ionizing radiation to give lethal or sublethal DNA damage to the cell to try and again... give catastrophic damage enough to kill the cell. So effectively we rely on radiotherapy because different tumours and normal tissues have different radio sensitivity and also you've got to remember that not all tumours can be particularly radio sensitive so you can't use radiotherapy reliably for all tumours and it will very much depend on the tissue. And there's three main types again. This is all evolving, but most of the time that you will know will be external beam radiotherapy, so that's EBRT. That's when you have an external radiotherapy machine that delivers radiotherapy. Brachytherapy is actually where we implant a radiation source into the person and effectively get a localised radiation dose. And that's used in prostate and cervical cancer, some examples. And you can also give intravenous injections of radioactive isotopes as well. So as I mentioned, most of radiotherapy currently given is external radiotherapy and is fractionated. So it means it's given in smaller doses, the whole radiotherapy dose is divided up and is given every day, Monday to Friday, over a period of weeks. And of course, there are now advanced treatment techniques, anything from, you know, Cybini for example or proton beam therapy so they're definitely evolving things and at the moment but you just need to know the basics and of course chemotherapy and radiotherapy will affect normal tissue so therefore the number of different side effects and you can see here and anything you don't recognize you can always look up but effective anything with the nitis as you know will be inflammation and there's a whole range of different side effects that will vary depending on what kind of chemotherapy is given and also what is the target for radiotherapy is which organ or area is affected. Of course the major problem with radiotherapy and chemotherapy that we have is that it will preferentially affect the really fast dividing cells but cancer stem cells don't divide as often. and can be relatively resistant and can go into kind of a dormancy or sleeper state and then confer risk of late recurrence. So moving on from chemotherapy and radiotherapy going into endocrine therapy principles, really drugs within this setting aim to either block hormone production, block the binding of the hormone to its receptor or provide a different hormone that counteracts. the driver hormone and again that's kind of new and it's a little bit less explored so most of them tend to be really of the first two points. So in breast cancer, we tend to look at CIRMs, and that's selective oestrogen receptor modulators. They are the things that will effectively bind to the oestrogen receptor and modulate its function. So they're usually antagonists in the breast in particular, but can have partial activating effects in other tissue. So tamoxifen, for example, is an antagonist in the breast, but it can be an agonist in the womb tissue, which is why people can get an increased risk of endometrial cancer with tamoxifen, even though it obviously acts as an anti-breast cancer agent. There are also aromatase inhibitors, and they actually block the aromatase enzyme that's required for us to convert our androgens into the estrogens. And they're mainly used in postmenopausal women. And when we're using them in premenopausal women, they usually need an ovulation blocker. So things like Zolidex, for example. And then you can use them in premenopausal women. And there's also estrogen receptor antagonists such as falvestrant. And there's new drugs coming on the market. So there's recent approval for a new CIRM, a new selective estrogen receptor modulator. and lecestrin that you might see out there as well. Prostate cancer is another area where we do use endocrine therapy and you can see the different examples down here. The things you will see most often are GnRH agonists, so things like gossirelin, you will see bicalutamide quite often, they're androgen receptor antagonists. And you'll see some of the other ones as well. Ketoconazole is very rarely used. It really is not used at all these days. But the others you will see. And there are, of course, side effects of all of those. So tamoxifen neuromatase inhibitors, you will see most side effects here. All of the common menopausal side effects and some of the extras on top. So ovarian function suppression. things like gossirelin or Zolidex injections where you would just literally switch off the ovaries and that results in very rapid onset of early menopause so that's important one to be aware of and what I will do is I will give you a copy of the slides that I did for menopause management in cancer I will give you a copy of those slides from band on the portal you So you can look at those in more details in terms of management. Androgen receptor, you've got to remember that it's really, really common to effectively put someone into andropause and also have all of the problems with metabolic and cardiovascular side effects from that. So it's really important to monitor patients who go on to this. So just be mindful of that. So hot flushes are quite common, osteoporosis, fatigue. depression, erectile dysfunction, but also metabolic syndrome is very, very common. You will see someone who has normal metabolic markers suddenly go into metabolic syndrome reasonably quickly, sometimes with prostate cancer treatment. So you need to manage that. Targeted therapies, kind of moving on from endocrine treatment, there are many, many of those. Again, you don't need to know all of them, but they effectively aim to target a specific either enzyme or receptor. or another drug target to try and again get an anti-cancer effect. And I've given you just a few examples here. So anti-HER2 drugs are common, particularly in breast, but they're relevant to some of the other cancers. So that's your Herceptin or Perjeta. You've got tyrosine kinase inhibitors, which are all the different IBS, so Vimurafenib for melanoma, etc., etc. Anti-VEGF is Avastin, again, commonly used in a whole range of cancers. PARP inhibitors in BRCA mutations and also in different cancers where we see problems with DNA repair that will allow us to use PARP inhibitors. And I said many more so you can read up on Cancer Research UK. So moving on to immunotherapy, this has been the biggest break through really in cancer treatment for decades. And this... Particularly within the setting of solid tumours, we know that the solid tumour environment can be quite immunosuppressive as the cancer cells try and co-opt their neighbours into effectively hiding from the immune system. So within the solid tumours in particular, we are aiming to lift immune suppression that's within that tumour microenvironment. But of course, by doing that, we can also carry a risk of autoimmune disease as well as all the other side effects. particularly the inflammatory ones, so all the different itises. So in clinical practice, the immunotherapy can be very varied. So the one that I've talked about in terms of lifting immune suppression are called immune checkpoint inhibitors or ICIs, and they're targeted at different targets. And you can look at that video from Cancer Research UK that will explain that a little bit. We can also now engineer very precise therapy. is that are completely personalised and we use them in blood cancer. So particularly with ALL children and B-cell lymphoma, so diffuse large B-cell lymphoma in particular, we can actually design a specific T-cell antigen receptor therapy that we can re-infuse into people. Now, there are high risk therapies that are very expensive. So they're usually used not. too upfront in the treatment but it's important to be aware of those. We can also use cytokines although that's a reasonably probably older approach these days. From point of view of the medics the patient selection is very important because we need to select the right patients because they're expensive drugs with significant side effects but they can also work amazingly well and there are many new developers in the pipelines various personalized treatments cancer vaccines etc And there's a book here if you want to know a little bit more about immunotherapy. So bone marrow transplantation, again, there are different ways of accomplishing that in detail, but in broad brushstrokes, we effectively need to find a matching donor. And then we need to collect the sample, what we're going to transplant from the donor. And then we're going to process it and that's going to get re-infused in the patient, but the patient has to first be conditioned. So it means they're usually receiving high-dose chemotherapy, plus or minus radiation therapy, to kill off as many of the remaining cancer cells as possible, but also kill off the immune system so that the transplant will take and you have less chance of reaction. So that infusion is done. And then we hope that the graft, will take. And that's important because there's also different complications of this sort of treatment, including graft versus host disease, etc. So I'm not going to go into full details of it. If you're particularly interested within, have a particular interest in this area, please read these two guides. The US guide, I think, is very good. UK guide is good too, but it's quite long. So do dip in and out if you're interested in this setting. It's a really specialist area, so I would be very cautious in supporting people around this. And really, we are looking at nutritional support here. We don't want to interfere with the process in any way. So how do we pick out all of this massive array of different treatments? Well, we have treatment algorithms that are recommended by different guidelines where professional panels have evaluated all the evidence and they make recommendations how we should treat people in specific settings. So these are examples of treatment algorithms from an organisation called ESMO and this is the European Society of Medical Oncology and in the US that's usually ASCO so that's American Society of Clinical Oncology and they will also recommend treatment in a specific way. Now you've got to remember that just because something is approved it doesn't mean it's going to get into the algorithm straight away and also it doesn't mean that NICE can approve its use in the NHS. So we've got to remember that particularly within the NHS in the UK system that treatments are evaluated in the base of cost effectiveness not necessarily effectiveness alone and there's thresholds for the treatments to be recommended. So sometimes the treatment may be approved, but is not accessible on the NHS. So as I said, this is just example for early invasive breast cancer. And this will all change. So every couple of years, there'll be an update because we have new evolving evidence here, for example. And as you can see, this is for advanced breast cancer. So again, it's breaking it down into different subtypes. And even, you know, looking at this, for example, triple negative. You can see it's chemotherapy, but actually these days we're now using immunotherapy much more now. So all of this will be changing and this is what oncologists have to keep up with and there's a lot of work being done on that. So you don't need to keep up with it, but you just need to know that there are guidelines that oncologists and MDTs, the multispeed teams, follow to decide what treatment comes next effectively for people. And as I mentioned to you, when we give treatment, we do need to assess response. And the RASIST criteria tend to be used usually within clinical trials, but in general gives you an idea for when we scan people after treatment, what are we looking for? Are we looking at a complete radiological response? So on the scan, we don't see anything. Partial response. progressive disease and stable disease. So you don't again need to know all of these criteria, but gives you an idea of what the team looks at when they're establishing whether the treatment is working or not working. So the techniques to really look at the response to assess response will be as a radiological response on imaging, so CT, PET-CT, MRI, etc. We've got to be aware of the fact that CT and PET-CT have significant radiation exposure. An MRI doesn't have radiation but still requires a contrast injection usually for the best resolution effectively. When we have surgery, we can also look at whether there are any cancer cells remaining. So that's pathological response. And in some cancers, there are different tumor markers that are used alongside this. And now with the novel techniques, we can also look at circulating tumour cell DNA and circulating tumour cells themselves and the different clusters to see whether we have any residual really, really tiny microscopic disease that's still detectable. So that's called minimal residual disease as well. And it's really important just to kind of going back to the tumour markers that no tumour marker can really replace imaging. Lots of them are non-specific. So CE125 is elevated in ovarian cancer, but can also be elevated when someone has endometriosis, for example. So very non-specific and can be elevated even if someone doesn't have a malignancy. And it's really about the trends, so the measurements that are taking place over time rather than a single value in most cases. So just give you an idea of what... as some of the images might look like, the MRI looks like this from a breast MRI perspective, and you can clearly see the tumour here on the right with its vasculature. PET CT looks like this, this is obviously really extensive disease as you can see, so the hot spots that you can see here, the sort of bright lit up spots are all cancer activity. So, How do we make decisions really when changing treatment? If the response isn't good enough, what do we do next really? Or when we are deciding on treatment in the first place? We use the MDT input and that means the team gets together, the oncologist, the surgeon, the radiologist, the pathologist, as well as the nurse specialist and anybody else who needs to be involved. They get together. They look at the imaging, they look at the blood test, look at the clinical picture and they will take into account the guidelines and any other test results to come up with a treatment recommendation as a team. So this is why usually when someone has a scan they need to first go, the scans need to go to the MDT meeting first before the treatment recommendation is made and before the client or patient has a meeting with an oncologist or the surgeon afterwards to decide on further changes. So guidelines, as I said, there are professional organisations that issue guidelines, so ESMO and ASCO being really common, but there's others as well, and NICE issues what is going to be funded in the NHS and that's really crucial for access for us. Established genomic biopsy scores can also be used in or advanced molecular profiling depending on the cancer and what's available. So Oncotype DX is used quite frequently in early stage hormone receptor positive breast cancer, so ER plus, HER2 minus. And you can read up about that so we can actually determine through a genomic score whether someone is high risk or low risk and whether they will require further treatment or whether they will be okay with the baseline treatment. We also now have liquid biopsies for metastatic cancers, so GARDEN360 for circulating tumour DNA or Data Cancer Genetics have a number of profiles for circulating tumour cells and they're approved by most private insurance usually by the oncologist. So we we do use them quite a lot and I use them in clinic as well and that can be very useful in the right setting. So apart from all of these medications and treatments that we need to think about, we need to also remember that people might be on other medications, particularly when we're doing interaction checks. So clients undergoing chemo might be on pain meds, they might be on anti-nausea medications or anti-emetics. If they are on opiates, so codeine or morphine type drugs, they will constipate someone, so they will need laxatives to cope with that. And they can also be nauseous, so they will get the anti-emetics. Steroids are used quite a lot, particularly with taxane-based chemotherapy like Paclitaxel. Bone protection medications are often being used, so bisphosphonate, so denosumab, and all sorts of other things. So it's really important that you get the full list of both over-the-counter and prescription medications from the person so you can properly check interactions for everything. So if you want to find out a little bit more about specific cancers and the different drugs, then here are some links to some of the guidelines. And for individual cancer treatments that you're going to encounter, Macmillan is an excellent resource. So when you see someone in clinic, you can just look up their drug online. You'll learn a little bit about and build up your knowledge. And you'll also know what kind of side effects they might experience. And homework for you. Here are some patient guides from ESMO, which I find really useful. And these are guides for patients, so they're written in reasonably plain language. So pick one or two, the ones that interest you the most, and do read through them because they give you a good idea of what people need to consider during their cancer treatment. Do learn as you go along. Try not to get overwhelmed by the amount of drugs and everything out there. You will pick it up. Just pick one area or a couple of chemo drugs or a couple of other drugs that you are most likely going to see or that you've heard people talk about and just learn as you go along. It all links up together and you will have a strong body of knowledge as you go along. ________________ 2.2 Troubleshooting Common Problems During Cancer Treatment Hello everyone and welcome to Troubleshooting Common Problems During Breast Cancer Treatment. So this is the lecture for the Breast Cancer Advanced Practice module. So I thought it'd be useful for us to sort of go back and just really think about what the aims of nutrition support are during treatment. Now really what we want to do is start from the very beginning in terms of pre-treatment, go through treatment phase and any breaks that the person might have during their treatments and then for primary cancers. come out of the other end and support recovery. So it starts with rehabilitation, optimising the client's health prior to surgical and medical treatment and the aim here is to reduce the risk of complication and enhance recovery. Reduce the risk of and help manage the different side effects of conventional therapy whether we are talking about chemotherapy, endocrine therapy, that's hormone therapy such as tamoxifen and vomitus inhibitors or more targeted therapies and immunotherapy. We want to support better treatment outcomes by supporting the client's overall well-being. That covers their physical, mental, emotional, psychological needs. And ideally, where possible, we would want to synergise and support the chosen treatment modalities that have been recommended by the oncology team. And as I mentioned, the aims between primary and secondary cancer are of course different. Where in primary cancer, we also would be wanting to support recovery after active treatment and help manage the risk of recurrence. And as we know, for many of our breast cancer ladies, that includes assisting with the side effects of long-term treatment that people might be on for five to ten years, and that includes hormone treatment. And for secondary cancer, as someone who will be on and off treatment for the rest of their life, really, we would want to support the best quality and quantity of life for the client and their physical and emotional resilience through treatment cycles or low-dose continuous therapy. And it sort of very much depends on how you can manage the roller coaster of secondary cancer together in your relationship and be supportive. Okay, so the next part is really going to be about general principles. As you know, I'm a big advocate for nutrition lifestyle first, always. Really, if we don't have those things right, then no matter what kind of fancy supplementation regime someone might be on, or off-label drugs or whatever else they're doing, it's really not going to land on the right soil. So nutrition, physical activity, stress management, psycho-emotional well-being and sleep should be supported always. And then really, if we're looking at a particular supplementation, we want to keep it targeted at supporting the current stage of treatment and side effects, and also really looking at the systems approach to cancer model more widely. And reviewing it, revising it regularly and targeting the bits that really jump out at you. And don't forget, with regard to supplementation, if in doubt, do leave it out. And more supplements with long, long lists of things are not better. We need to opt for targeted and supportive approaches that really minimize the burden on the client, both financially and in terms of taking so many pills. I know people come to me sometimes on 20, 30. various different supplements with huge pill loads and actually this they are struggling to fit in food so you really need to think about how you can optimize someone and really do it in a targeting supportive way and dynamically change through the different phases of treatment we really must always check interactions thoroughly and document what you find so if you found something that was you know cd grade evidence but you chose to dismiss it because it wasn't clinically relevant then it's always good for your own notes to document that you found it and you dismissed it. And of course, for anything that has, you know, level A or B, you would need to take it into account and omit it. And I would ask the client to disclose to the clinical team what they're taking. Of course, it's up to them to do so, but it is really important that everybody is informed about what's going on. And, you know, we quite often collaborate and talk to pharmacists who have some concerns. And usually we're able to come to a mutual. agreement about what may be helpful and what's not. And this is absolutely essential if anybody's in a clinical trial. And a clinical trial really is nutrition lifestyle. And if any supplements are given, really they're sticking to replacing nutrient deficiencies. Most of the time they're not allowed to add any other supplementation unless it's prescribed by a medical doctor usually. If you are going to be writing to the medical team to update them on what you're doing, please keep it brief to the point and make sure that you're supported well by evidence and emphasise in the fact that you're caring for the whole person. You really are supporting their health, you're not treating their cancer because that's a medical. team's job and you're supporting their overall well-being during treatment to help to your ability because of course all of us certainly from the medical professional front would want to make sure that people are as well supported as possible and that means that they can be more compliant with treatment as well. So what I'm going to be talking about in the next few sections looking at different options, broad classes of treatment. You need to remember this is general information, you need to combine it with specific breast cancer type information as needed and I do hope this is going to be one of the most used lectures and materials for you because if you see a new client with breast cancer, print off that specific breast cancer type handout as well as this handout and I think you'll be in reasonable hands about knowing where to start. And of course always prioritize and personalize, we are talking about the person not just that cancer. We have, I think, discussed this before, but really it is very important that you have a disclaimer with regard to the Cancer Act. Some on your website and paperwork, because it's really important that people understand the information that's provided by nutritional therapists is not a substitute for medical advice. And that nutritional therapy does not claim to diagnose, treat or cure any disease, including cancer. And that's essential. So let's dive into surgery. Those of you who've done the foundation training with me would be very familiar with it anyway, but there's a few additions for breast cancer specifically. So assessment, really nutritional physical assessment, and for you, of course, you're not going to be doing a detailed physical assessment, but just ask them what can they do daily in terms of movement and activities of daily living, and if they do any regular exercise and what. And ideally, we would want to refer to a cancer access specialist if possible or as soon as possible. And if one to one is not possible because of budget, then Pennybourne UK has online classes with cancer access specialists that people can jump into. And there might be other options available via local charities as well. So do look those up. Nutrition at a basic level, really without diving into the specifics, really just making sure they have sufficient protein, zinc, omega-3 and fat-soluble vitamin intake. And do remember that protein requirements will go up after surgery, but they might not feel like eating very much, depending on what kind of painkillers they're on, etc. So blood tests at minimum, we would want to do a full blood count, liver and kidney function. And we would want to do a metabolic profile, so Hb1c, fasting glucose, fasting lipids. You would want to know the inflammatory status. Ideally, if we had the time, we'd want to optimize that. And that's CRP plus or minus ESR. And of course, you would be calculating your NLR and PLR as well from the full blood count, which will be covered more in the immune module if you haven't watched that already. And those of you who have done foundation training with me will have notes on that. Iron profile, vitamins D, B12 and folate are important, quite often are obtainable via the NHS if we ask for a specific reason. And do remember to ask people to omit supplements, otherwise you're not going to get a good result, really an accurate result. And I tend to ask people to omit relevant supplements for three days before the blood test. That mainly will cover most things. And if you are suspecting deficiencies due to poor dietary intake or nutrition diet, of course, consider testing to optimise that in advance as well. And depending on what the systems approach model says to you, you might want to do other assessments as well. But that's kind of a general approach. So one of the common concerns around surgery is if someone's already anemic, because they're going to be suffering from further blood loss. usually as a result of the operation. So we'd want to optimize that if we get the time prior to surgery. And the assessment of any anemia must be based on both full blood count with the differential, but also with the iron profile and B12 folate on the cysteine serum or oat markers, looking at particularly those methylation nutrients. So you've got to remember that both iron, B12, and folate are all required to maintain normal red blood cell production. So either of those things can affect the way that people are manufacturing their red cells. And do remember that if someone has a highly elevated inflammatory marker, such as CRP, ferritin will not be accurate as a marker of iron storage status. It will go up in line with the CRP. Because it's an acute phase protein that's manufactured by the liver in response to an inflammatory stimulus. So do keep an eye on the fact that, of course, that's why we use sometimes ferritin as an inflammatory marker alongside CRP with or without ESR. So do just keep an eye on that. So if you see someone and maybe their ferritin is 35, but their CRP is well over 20, their real ferritin is probably quite a lot lower than that, because they're quite inflamed, so they're pushing their ferritin up. Ceramine is not really reliable as a mark of iron status. It fluctuates hugely in response to dietary intake. So for example, if you had a high iron meal, you will find that your ceramine will be elevated temporarily. And then it will go through the normal iron metabolism storage and you will calm down. But it is important to let people know not to eat a high iron meal before you do the bloods as well. And quite often places like MediChex, etc. will have instructions on that. Sometimes people get a little bit confused about MCV, which is the mean cell volume, which is kind of how an average volume of a red cell. And. Sometimes if the MCV is abnormal, too high or too low, people will say, well, they're anemic. Well, they're not anemic unless the hemoglobin is low. So no matter what the MCV is doing, if the hemoglobin is not low, they're not anemic. So do remember that you can have iron deficiency without necessarily being anemic. And do remember that iron should not be given automatically. It is pro-oxidant, pro-inflammatory and can promote dysbiosis. Doesn't mean we don't give iron. We do when it's necessary, but we give the minimal dose for the smallest amount possible in terms of time. And we monitor carefully for a return to normal status. What was interesting is there was a... So for example... So what's interesting is there was a 2020 study that looked at a number of different supplements and they used during chemotherapy and the use of iron during chemotherapy was significantly associated with the risk of recurrence. Now what I would say to you is that quite often of course people who are sicker might be more prone to getting more anemia and also require more iron replacement. So that might be a feature of that rather than the iron itself. However, we do know that excessive iron can promote dysbiosis. is pro-inflammatory. So we would want to make sure we are using it rationally and appropriately in this situation. So if you have a low hemoglobin in front of you and someone has a low MCVUAMCH, which is the mean cell hemoglobin, usually this is due to iron deficiency anemia. There sometimes are other causes, but usually that's due to that. And it would be usually accompanied by low ferritin under 35. And for me, for women of reproductive age, I normally aim for for 35 to 75 on the ferritin, and it will go higher quite often postmenopausally. And usually you will have low transferrin saturation, so you know that both iron storage indicated by ferritin and iron transport indicated by transferrin saturation are compromised. So you have a number of different options from that perspective. You can consider lactoferrin with meals. You're looking at 250, 300 milligrams once or twice daily, and it has to be given with an iron-rich meal. That's really important because... We sometimes use lactoferrin away from meals, really to regulate high ferritin as well. So here we're using lactoferrin as a support of iron absorption and use by the body. Temporary iron replacement with vitamin C, again, trying to go the lowest dose possible for the shortest amount of time possible, and possibly combined with probiotics. So I quite like IronBion Plus for low dose replacement. It has a low dose of iron and... a probiotic with it that aids iron absorption in general so it can be quite a good choice sometimes and you're reassessing four to six weeks and reassessment should be based on the iron profile here as well as full blood count but do be aware that hemoglobin can occasionally usually take longer than that to come up, more like six to eight weeks. So anemia, just do a quick case study for you. So this was a 55-year-old patient of mine with metastatic breast cancer on metronomic therapy. And. And she had a horrible lower respiratory tract infection. She actually got a really bad pneumonia called pneumocystis carinii pneumonia. And she was treated for that as an inpatient with IV and oral antibiotics for about three weeks duration in total, probably slightly more than that. She was discharged home with resolving infection or antibiotics. So she had another week out of those three weeks at home. But she had. Really still a lot of fatigue, some phlegm, some worsening lymphedema and alternating constipation and diarrhea. And her diet did not change in any way, shape or form. And she did not, prior to this respiratory tract infection, have any iron deficiency. It was tested and confirmed. And the CRP was discharged. It was actually lower than what we tested. So here you are seeing the bloods well after. discharge. So it's about two weeks in at home. And you can see hemoglobin is low. She's inflamed. So ESI is elevated. CRP is elevated. Platelets are elevated. And that's because of the inflammation. You can see that her iron status is low. Ferritin is 20. Transferrin saturation is very low at 8. And actually even her serum ion is on the low side. So the intervention here was, why on earth was that? patient iron deficient anyway was the first question to ask because she wasn't previously her food did not change significantly so my suspicion here was that the antibiotic disrupted the gut microbiome and her iron absorption was further compromised in addition to that by the inflammation because inflammation actually reduces your iron absorption from the GI tract so I look to target the underlying processes rather than just load her with iron So we did some anti-inflammatory and gut microbiome support from the food perspective. She was given some anti-inflammatory supplementation and iron biome plus for one pack only. And you can see here, this was just under four weeks in terms of results, and her iron profile is entirely normal. So that's just under four weeks with very low dose iron replacement with probiotics and anti-inflammatory support. And you will see hemoglobin hasn't come up yet, but actually it was back to normal four weeks after this when we repeated the bloods. And you will see one thing that did go up is RDW, that's red cell distribution widths, and that's like the range between the smallest red cell and kind of the biggest red cell. And that can quite often go up as the blood count starts recovering, so don't be worried about that, it will normally go back down as the hemoglobin recovers. But you can see how much impact you can have with relatively small interventions from our perspective. So low haemoglobin with high MCV and MCH most commonly is due to B12 or foliar deficiency. So you always need to test for what it is and think, are there any medications, metformin being one of them, that might be compromising the person? What about dietary intake? Are they on a plant-based diet and are not actually supplementing B12 properly? And you can also of course test homocysteine and MMA if the usual bloods are not entirely clear because as we know B12 or active B12 is still not the best assessment for B12 and I do like MMA for that. Now low haemoglobin but coming up as well as having high MCV and MCH can also occur during blood count recovery because the cells that are released from the bone marrow at that point are called reticulocytes. And reticulocyte is a mature red cell that are quite large, so quite often they can push up the average volume from that perspective. So just be mindful of that. It can occur temporarily, but then I would usually expect that to resolve within about four to six weeks. You can also get a picture of low haemoglobin, high MCV, MCH with hemolytic anemia, bone marrow failure, liver disease and hypothyroidism, among other causes, but they're a lot less common. If you have a low hemoglobin but normal MCV and MCH, that's really quite common. And most commonly it would be due to anemia of chronic disease, and that's quite often present in metastatic cancer, because the cancer process itself suppresses normal bone marrow function. And it can also be a particular issue in those with very high inflammatory markers, because, again, the inflammation suppresses normal bone marrow function and production of red cells. And you might also see it in your clients with autoimmune disease. And this can be quite profound as well when there's bone marrow infiltration by the tumour, and there are some breast cancers that do infiltrate the bone marrow, and then you quite often get what we call pancytopenias, and that's all cells are low effectively. Platelets are low, white cell count is low, hemoglobin is low. But generally if this low hemoglobin with normal MCVMCH is due to the anemia of chronic disease or cancer-related anemia, it will only improve with the better control of the underlying process. So ultimately, cancer treatment will, funnily enough, raise their hemoglobin, not lower it. But that's because better cancer control means the suppression of the bone marrow function is lifted. Also, this sort of picture can occur as a result of bone marrow suppression by various medications. And don't forget, you can also have mixed deficiency. You don't have to have just B12 and folate. or iron, you can have all of them combined that will give you a normal MCV quite often. So in terms of anaemia again, optimising people before surgery is really important, but of course we need to look at the wider aspects of prehabilitation. And prehabilitation is that practice of enhancing a patient's functional capacity before surgery. For surgery, or ideally, we want to talk about any medical treatment, including chemotherapy and immunotherapy, with the aim of improving clinical outcomes. And it could be post-operative or post-treatment outcomes more broadly. As you can see here, the BMJ has a much broader definition, which I much prefer, really. It talks about optimising not just functional capacity, but both physical and mental health. And it's through needs-based prescribing of exercise, nutrition, psychological interventions. A multimodal approach is always going to be more effective. So collaboration is key. And really, we are wanting to actually support people in actively taking part in preparation for treatment to help support their sense of control purpose and develop resilience. So some general rehabilitation considerations, of course, nutritional optimization. So we know we want to go with a colourful, anti-inflammatory, whole food-based diet as a baseline, then adjusted depending on the individual. Smoking cessation is absolutely crucial. Support your clients as much as humanly possible because that does affect surgical outcomes. And of course, alcohol reduction or cessation as well. Physical activity can be divided into total body exercise, which will be important. So cardiorespiratory fitness through cardiovascular exercise and aerobic exercise is... really, really important to be able to go through a long operation, particularly successfully. And anaesthetists love optimising people with aerobic exercise. But you might also want to be thinking about doing regional exercises, local exercise, depending on the treatment deficits as well. And it's really, really important for us to keep an eye on both of those. But of course, you won't be doing that yourself. You will be referring along to maybe a cancer specialist physiotherapist or a cancer expert specialist. Stress reduction psychosocial support and of course medication and comorbidity review. And that's just any other diagnosis someone might have apart from cancer that do need to be reviewed and optimised. For example, if someone has diabetes, that needs to be optimised. If someone has thyroid issues, that needs to be optimised. We need to make sure we keep asking for medical reviews as much as possible and the medics need to keep a broad view and of course as we discussed appropriate management of anemia so not just giving people iron randomly hoping it will fix all anemias because not all anemias are created equal and depending on the MCV they will have different causes for what's going on. So as a starting point from a nutritional perspective of course remove or reduce things that we talked about before. you know processed foods processed meat sugar sweetened drinks refined sugars damaged processed fats alcohol and usually i do tell people to stop eating grapefruit if they like it because there's far too much interaction potential in terms of the cp3a4 etc so i do tell them that's one food that will probably emit moderate caffeine so you know for example if someone has no issues with anxiety to always coffee well okay you can have one or two cups of organic coffee with meals but not overdoing it and do remember that actually roasted coffee beans can be a source of acrylamide as well as some of the concerns that people might have around coffee and mycotoxins these days so other things of course we want to be talking about is you know pfc balanced meals we want to be getting it as anti-inflammatory as possible and having a half plate of rainbow vegetables lower sugar fruit lots and lots of herbs and spices and anti-inflammatory fat balance and you know We've, I think, covered the dairy and soy, but do ask any questions if you need to. But really, there's no evidence that soy, if it's organic, fermented and consumed in normal dietary amounts, is harmful to anybody. From that perspective, whether they do or don't have breast cancer. And dairy, again, organic fermented, does not appear to have an impact in the same way as, for example, pure milk does. So the dairy... In particular, milk consumption can drive IGF-1, but actually it's not the same for yogurt. So just something to keep in mind. Protein, we talked about already. Organic whenever possible. And do give people lists for their dirty dozen, clean 15, because of course we can't always afford organic produce for everything. So it's important to give people choices. Clean hydration, very, very important, particularly when people might be. Later on, suffering with constipation because of the painkillers they're given post-surgery, so getting them well hydrated in the first place is important, and they can continue with that when they come out of hospital and when they're in hospital. So, you know, clean filtered water, green herbal teas, and of course if they're obese or malnourished or, you know, have a particularly low BMI, you need to opt for it. ...specifically as needed. Here are some of the smoking alcohol resources. I'm not going to go into great detail, but you can obviously look some up. And I do suggest you actually look at them yourself so that you know what you're recommending. And for alcohol, the other thing that I don't have on here that will be useful... useful is that Drink Aware app is quite useful for people to realize just how much they're drinking and it is just a quick reminder about alcohol and breast cancer risk which is quite useful to counsel people around alcohol production. So physical activity, NHS might provide a physiotherapy, a local pre-hub programme. They're not very well established everywhere. So local provision does vary significantly. Private, if people have an option to go privately, there's cancer experts, especially yoga therapists who work with cancer. And of course, free resources, it might be yoga for cancer class. It was Vicky Fox in Pennyborn, UK as well, as I mentioned before, will also have physical activity. classes online. So no matter where you are, you should be able to engage. And really, I would not use normal PT. I mean, there may be some tiny circumstances, but I really wouldn't. I would want someone to work specifically with people who are aware of cancer diagnosis, particularly with those lymphedema risks, if anybody's had any kind of auxiliary work done, as well as radiotherapy. So stress reduction sleep, again, you will be familiar with that from my other talks, but breath work, mindfulness, time in nature, sleep. hygiene and there's some really good free resources so Sleepio CBTI is available free on the NHS and has good evidence so it's something definitely to try with people and of course do be mindful of trauma and the need to refer for proper trauma work not for counselling or general therapy whenever possible because trauma needs to be treated very differently. Psychosocial support is quite often offered by various charities you know breast cancer charities specifically but also you know Macmillan local charities on your care etc yes to life and i would be a bit cautious with incident groups if people are engaging just remind them to put clear boundaries around things and also remember that their situation is going to be different to somebody else's so surgical complications you can read this i don't really need to go through it but really just something to be aware of is of course as you will know from the lectures previously lymphedema is lifelong risk so people need to be aware of that and also in in terms of late complications of functional impairment after surgery or cording, it would be really important to undergo physiotherapy for cording, for example. The scar work is really helpful. So Emma Hollywood Restore Scar Therapy is fantastic. She's in London, but you can also get access to her trainees. So Octavia at Synthesis has trained with her. And you can start that sort of work six weeks post-operatively. And if we... really does make a huge difference to women. So looking at, as I said, perioperative support from the nutritional perspective, is there anything else? A full rehabilitation program, as we talked about, would be ideal. I know not everybody can engage with that, but as much as you can get. You want to optimize zinc status to support postoperative healing, apart from the fact that you are doing normal nutritional optimization that we've talked about before. You might consider MCP really. The human studies are only done around PSA and prostate, but we use it as a part of kind of galactin-3 inhibition, potentially before and after surgery, just because it's an opportunity for spread, really. And I would love to see more trials on this. So this is something that I really use much more on a clinical basis, a clinical experience basis, that I find that helpful, but rather than insignificant data. And, of course, be very careful. very careful with supplements around surgery, amid those that may affect bleeding or clotting, you can check the natural medicines database for that. But here are some common examples. Make sure they are well prepared, you know, they know what's going to happen, they have a positive attitude, they have their hospital backpacked, and they know how to manage stress. And there might be sometimes some medical things that we can do around resection because it can be immune dysfunction, facilitated metastases, but really that's not something that you would get involved with. non-medics. So following surgery, if people have come home and they don't have any unusual complications, don't give the usual detox supplements just because, you know, you can give things like silyomarin in the run-up to surgery and after surgery, but no major detox programs because people are quite often got enough to deal with and also you don't want to be mobilizing someone's toxic load in and around a vulnerable time. So really first two weeks you're just going to talk about... whole food based regime. Easy, nutritious, full of colour, really anti-inflammatory, supporting tissue healing with supplementation as appropriate, depending on their nutrition, protein intake. And then do be mindful of the fact that they might be given opiates or other things after surgery for pain management. So you want to preemptively manage things like constipation. Early physical rehabilitation, they will have had guidance from their medical team. So making sure they do it regularly. And then usually after four weeks, you can start doing things like, you know, just supporting normal circulation, really. Things like exercise, infrared saunas, etc. And I mentioned scar work already. And you can also use things like topical vitamin and rosehip oil with a few drops of the essential oil, provided they're not sensitive and they're well diluted. So in terms of clinical experience, again, this is not based on great clinical evidence or any trials. This is something that we do, not in everyone, but may be useful to consider cinnamomium for hepatic protection. And some of the considerations around trying to really manage that inflammatory aftermath of surgery with some of the supplementation, depending on what else they're on, because, of course, you will need to check their interactions. Here are some of the references. And now we're going to go into chemotherapy. So you will see this assessment slide and I will refer to it quite a bit. It will still remain the same here in terms of nutritional physical assessment, but do particularly note that during chemotherapy, you would want to also note people's anthropometrics, so weight, BMI, waist to hip ratio, because they're very useful monitoring for both weight gain, weight loss and muscle loss and sarcopenic obesity that can happen in breast cancer chemotherapy. and help support recovery. It's really essential to manage any metabolic syndrome problems. So that's, you know, difficulties with lipids, waist to hip ratio, being abnormal, having high blood pressure, and having insulin resistance. They're really, really important because if you have metabolic syndrome before you enter even neoadjuvant chemotherapy, that predicts a lower complete response after treatment. So we'd want to optimize people as much as possible. Same blood as before really, and as I said, keep an eye on the overall systems approach model too. But do avoid unnecessary testing, so we wouldn't usually test the GI microbiome until really probably two to three months after chemotherapy the earliest, because ultimately there will be changes induced by treatment as well, and it won't change your management very much during treatment. So, you... In terms of antioxidants, it's a big controversy still from the supplementation perspective. So really, food is our safest and best long-term option, really focusing on as much antioxidant and anti-inflammatory nutrient intake from rainbow veg, low-sugar fruit, herbs and spices, herbal teas, etc. And in terms of supplementation, there's different studies I've listed here that some show no evidence of impact on survival. Some show there might be increased risk of recurrence potentially, or maybe increased risk of total mortality. We don't know. So in my case, I would avoid classical antioxidants and stick to non-classical antioxidants. And certainly we'll look at food first always. So fasting chemotherapy, really the usual regimes can be varied. But of course, we need to consider the overall picture. So only advise it if they're... Patient is robust, does not have a BMI of under 18, and they're not malnourished horribly anyway. And you need to keep in mind there are some people who are going to be really poor at regulating their blood sugar, so they might struggle with that full stop and you might need to work them up to it. So usual regimes are fasting for 24 to 36 hours before, 24 hours after. But, you know, any fasting really would be better than nothing. I always think that if people are really nervous about it, sometimes I would get them to do a reduced fast first. So maybe stop eating at lunchtime the day before chemo and don't eat until the day after chemo for terms of breakfast. So it still gives them something. It's about 36 hours as a fast. Not quite as good as 48 hours, but you will still get something and then work people up. It's quite interesting to see. There's some early research on combination approaches, so using, for example, intermittent fasting with herbal therapies such as ashwagandha. And there was some research in mice really that might be helpful for overcoming cisplatin resistance. So what's the space? Obviously, we don't have a human study on it, but it'd be interesting to see what people come up with. So FMD, fasting mimicking diet for three days around chemotherapy can be really useful. And there have been a number of studies on that. So there is some early evidence it might also help with immunotherapy, not just chemotherapy, and potentially can be used in people on endocrine therapy. So there's just some things to think about. FMDs are useful. I do tend to prefer whole food FMD rather than trying to do Prolon, but some people find the convenience of Prolon quite useful. And, you know, in terms of mechanism, we all know that that will change the insulin. insulin and glucose regulation, so it will reduce insulin IGF-1, usually. And also, the other things that we are thinking about, it could be that it enhances antitumor immunity because it changes the microenvironment of the tumor, but also the fact that it might play on the differential stress resistance. Basically, the normal cells can tolerate this amount of stress, but cancer cells are more susceptible to not being able to tolerate it. So, a few examples, and FMD and... And the intermittent fasting or time-restricted eating, TRE, have slightly different mechanisms, but it's quite interesting to see that can be acting immunologically as well. So here are some recent studies in breast cancer. You will see there's probably not a hugely impressive reduction in toxicity, maybe a little bit of GI toxicity, but a significant difference in metabolic parameters, and it appears the quality of life is good as well. And there's a new trial that's going to be up and coming. which could be really, really interesting. It's a multimodal intervention on 16-8 time-restricted eating in a healthy pattern and also reducing sedentary behavior during chemotherapy. So I look forward to those results when they're published. Ketogenic diet and chemotherapy, really consistent findings all include, unsurprisingly, better metabolic profile in terms of blood glucose levels, but there can be tolerability issues around nausea, fatigue, or constipation. It's an area of very active research. There's been a couple. of trials that I've listed here. But what I would say is that my personal preference is for Mediterranean-style anti-inflammatory ketogenic diet. So again, you don't really want to be overdoing saturated fats in the vast majority of patients. You still want to keep an overall anti-inflammatory profile, and that's how I would do it. And of course, other considerations, you might not need a ketogenic diet. You might go for a lower carbohydrate anti-inflammatory diet with net carbs of under 75. 100 whereas of course the ketogenic diet will restrict to 20-25 grams of net carbs or you know if people are really not up for it you know considering the general high fighting genitive inflammatory diet still has plenty of benefits. So here are some general ketogenic guidelines for cancer if you are with the IFM you can use the mito plant from there with different adaptations so you can just allow only one to two portions from starchy fruit, veg, fruit and grains to be on the CV. and that can push people over the edge. So you need to be very careful with portion sizes. So I tend to eliminate grades that stick to low sugar fruit and minimal starchy veg because you want to pack their diet full of normal starchy veg that are of all colours. So protein around one gram per kilogram. Again, you might go up further. And chemotherapy would go up to 1.2 gram per kilogram quite often because people have a high protein requirement in terms of healing and repair around 1.2 gram per kilogram. around that time. And again, it sort of depends on where you're at, how much physical activity someone's doing, et cetera. Net carbs, I've mentioned, usually we would tailor the amount of net carbohydrate that's monitored through a chronometer using Keto-Mojo. And we're looking at GKI, which is a glucose ketone index, and we're aiming for ideally therapeutic ketosis 1 to 3, but it's quite hard to achieve for a lot of people. So at minimum, nutritional ketosis with GKI of 3 to 6. and really fat should make up anything that's left over between protein and nut carbohydrates do be aware of the fact that it takes some time to get into ketosis usually I say to people you three days would probably be a sensible timeline for a number of people and sometimes can be take longer if someone's significantly metabolically compromised and people can get keto flu so feel really quite miserable getting into ketosis so you might use ketone esters, make sure they're well hydrated with electrolytes and you can also extend their fasting window to try and help them get them into ketosis faster. And ketogenic diets can be associated with things like nausea or constipation. For constipation, PHGG can be quite useful as a prebiotic powder added to things like ginger tea to help or ginger decoction to help with the nausea. So special considerations, I'm not going to go over all of these because we've mentioned some of the key... therapies before but With capicitabine, you would want to avoid folate supplementation because high serum folate has been associated with more complication, more side effects. So I tend to give things like Seeking Health B- if I need to give a B-complex during that kind of treatment so it avoids B12 and folate supplementation. And you might consider the 10% urea cream or lotion for Hand-Foot Syndrome, which is another common complication. They also need to keep their hands and feet nice and clean and dry. Anthracycline chemotherapy, so these are things like epirubicin and doxorubicin, do remember their cardiotoxicity, so probably the best evidence really is largely still in animals and breasts, but human evidence in children with leukaemia. The EPA and DHA combination can be cardioprotective in these drugs, a minimum 1000 milligrams per day. and you don't really want to go lower than that, it's very unlikely to have an effect. Usually I would give two to three grams of combined EPA, DHA for people who are going through this sort of treatment. There are other animal studies of various different supplements. I highlighted flaxseed because it's easy to incorporate and ultimately from our perspective it also has multiple effects on the gut microbiome. So I tend to recommend flaxseed not for its effects on cardiotoxicity necessarily, although there's some really promising evidence in animals for that, but it might as well have that effect because I'm also supporting their gut microbiome. I'm also looking to support their omega-3 status with a shorter chain, of course, omega-3s versus EPA and DHA, so it's a useful one to incorporate. Taxanes, of course neuropathy and nail changes are quite reasonably common among usual side effects of chemotherapy. So for nail changes polybalm can be useful, neuropathy we'll talk about in a second. And do remember the paclitaxel, unlike nab, paclitaxel does require steroids so they will have steroid-induced dysregulation in terms of metabolism so it can induce more insulin resistance and people can get a new diagnosis of pre-diabetes or diabetes during that time. and worsen, of course, their overall diabetic control if they are diabetic, and also can disrupt their sleep. So you do need to give them strategies, and sometimes they need to discuss a steroid dose with their medical team. Platinum agents, nephrotoxicity and neurotoxicity are most common among the different side effects of treatment. And do consider a referral to an integrative physician or private physician for melatonin. and really the effects of that are around neural protection, sleep, pain and fatigue benefits during chemotherapy and there are human RCTs for between 18 to 20 milligrams of melatonin showing a good effect. Of course that dose isn't given straight up, you titrate people up slowly. So in terms of side effects, low white cell count of course being really common, we talked about it in the video before. The German nutrition interventions have not been shown to be particularly effective here. So really here we want to be looking at multimodal interventions, so herbal medicine and other referrals. For example, MISLTO or VAE, that stands for viscum album extract. So you might want to go to Camp Hill, there's a Royal London Integrative Medicine Hospital. Synthesis obviously provides that as well, but we have limited availability because we have an incredibly busy clinic. Acupuncture with moxibustion can be useful and provides benefits for overall quality of life as well and occasionally maybe some TCM herbal medicine I do find it useful but unfortunately the herbal studies are often really poor quality and I also have provided you with some clinical experience notes later on. So with GI mucositis again probably not so much evidence certainly in breast cancer but we know zincarnosine can be used for another population so I do use that. and I will use things like for diarrhea, we will use some low dose probiotics sometimes. But generally it's also looking at the dietary management. Quite often people will need to have their diet optimised around diarrhea and they will often be given medications for that as well. Nausea and vomiting usually reasonably well managed and they can talk to a medical team by changing their medication if it's not. But there is really good evidence for acupuncture, electroacupuncture and acupressure. So do try and refer early around treatment to a proper TCM acupuncturist. Ideally, someone who has an experience with cancer. And people also find sometimes having those seasickness bands that are pressing on the P6, a pericardium 6 acupoint can be quite useful too. Not everybody though. I have to say actual proper acupuncture, electroacupuncture can be much more useful. Ginger relaxation techniques may be considered and glutamines not recommended in this setting. So for CIPM, that's chemotherapy-induced peripheral neuropathy, it's most commonly linked to taxon and platinum-based therapies. You should not use acetylalkarotene because actually that's been shown to potentially have a harmful effect. Omega-3 is important, that's definitely something we'd want to cover, both from a dietary perspective and potentially supplementation. My B complex evidence is variable. I have to say I do give it and I don't give B6 alone. I would always give it as a B complex and depending on whether there's capricitabine or other chemotherapy then I might be wanting to use different B complexes. But you do use a reasonable dose, so things like whole food B complexes rather than really high B12 doses. McLeo Labs does a B complex. Plus, or it also does not during chemotherapy because it has antioxidants in it. It also does a multivitamin complex. There are much more reasonable doses of some of the other B complexes out there. You don't want 18,000% of B12 in most patients with cancer. It's not appropriate. Here are some new reviews covering neuropathic pain and nutritional interventions. Do be mindful of the fact that a lot of these are aligned to an animal study. So we need human studies. So that's what I've focused on here. So there's a Japanese camp medicine that's showing potential benefit. Again, you'd need to refer for that. That's not something you'd manage yourself in clinic. Physical activity is really important. And here's the evidence from that perspective. In particular, emphasis on sensory motor training. So again, that's a referral you'd want to have. Acupuncture and fixology has been recommended in the recent SAO ASCO pain guideline. But it's really recommended as low quality of evidence. recommendation but do remember that requires sufficiently large randomized control trials and aren't as many of them in this area and so but i do find it beneficial i have to say clinically i do with a combination with fatty acids being useful and that's a clinical trial as well it's not a proper rct but certainly something to watch and i do give PEA if people start developing neuropathic symptoms and there would have been an omega-3 anyway so I'm kind of covering that and there's some interesting research around photobiomodulation that we need to watch the space for. So we talked about this, we need to talk about the CRF fatigue There are some recommendations around ginseng, hypnosis, acupuncture and yoga, and breast cancer, SAO guidelines which are quite old now but still useful. For me, movement is crucial. Really, exercise has a robust effect on cancer-related fatigue, whatever is manageable, and whatever might be manageable during different times of the chemotherapy cycle. And we also have seen in recent research and recent meta-analysis showed that and mistletoe therapy that you can refer for also has a measurable effect on fatigue and quality of life. Pranayama or breathwork can also improve potentially fatigue and quality of life, although not as much robust research as in exercise, but still useful in the context of yoga or yoga therapy. Chemo brain. So we need to be mindful of the fact there's risk factors for it, and particularly stuff that we would test for. with nutritional profiles that we do in terms of nutrigenetics. So variants in EPOE, COMT and BDNF can actually predispose individuals to higher risk of chemobrain. So if you already know someone has those, you need to watch it. Exercise is important and the evidence for it is here. And probiotics, quite interestingly, might play a role. So there was a recent trial in 2022 where they were given a combination supplement with bifidobacterium longum. lactobacillus acidophilus and enterococcus faecalis and they found actually significantly decreased chemo brain incidence in improved cognitive function as well as of course changing the gut microbiome and their metabolites so that's quite an interesting one we need to watch the space but of course don't give probiotics to people who are neutrophils are 1.2 and below that then basically there's a bit more risk here and i wouldn't intend to do it And of course, I would really love to see some proper trials looking at multimodal interventions, some obvious interventions such as omega-3, and unfortunately they haven't been done. For pain, really, it's a really complex issue, and there are a number of modalities we can consider, but really we need to know what the pain nature is, and that should be assessed by a pain specialist or the medical team. And there's new pain guidelines by SAO-ASA. So there are no breast cancer specific but very useful to be aware of and here are here they are so you can see that obviously joint pain we talked about in terms of rheumatism inhibitors so acupuncture as the kind of the strong recommendation in yoga is a weak recommendation there's general cancer pain so here you will see that for general cancer pain or musculoskeletal pain you'd want to look at acupuncture reflexology potentially the stronger recommendations massage a sort of moderate and then there's some other options as well that have a weaker strength of recommendation basically it very much depends on what you're looking at so from the pain perspective really this is quite a complex issue and really we want to be approaching it based on what kind of pain we're looking at and there's been some really great recent new guidelines by seo asking which i really suggest you read And this is a quick summary graphic from there. So as you can see for general cancer pain and musculoskeletal pain, acupuncture and orthopsy come out at the top with massage in the middle and then some other modalities we can use later on. So depending on the pain that we're looking at there are different interventions that we might want to use. Anxiety and stress, you will see strong evidence for meditation mindfulness based programs as well as evidence around yoga and music therapy. And then some other interventions might be considered, such as acupuncture massage and maybe breath work. And depression-free disturbances, again, you will see that there's very good evidence for meditation mindfulness-based programmes. So these are definitely the first-line things that I would recommend. And there might be some other solid evidence for yoga and yoga therapy. Yoga therapy has less of an evidence base because mainly it's less studied because it's difficult to study in a one-to-one setting. but also some evidence around massage and music therapy, although not as robust as we would probably have liked, because usually it's a very short-term effect, certainly from the massage perspective, and you might want to consider acupuncture as well, and of course physical activity is so, so important. So here are some of the general clinical experience of acupuncture therapy that I have. I'm not going to read through those, but you are welcome to look at them in your own time. and consider how you do those and it is important to know that we usually aim not to supplement during 24 hours before and after chemotherapy because of course they might be fast anyway and of course you can consider multiple things below but you need to check the appropriateness of this based on your systems through the systems approach model and also interactions with current treatment so post treatment after you've gone through the chemotherapy Really, we want to be reassessing bloods at four to six weeks after completion. And they'll probably be very similar bloods you would have done for the pre-treatment assessment. We would want to reassess other model areas as necessary, giving people enough time after chemotherapy provided. Of course, this is their last treatment because they might be going on to other treatment. And of course, nutrition lifestyle optimisation is key, but there may be other referrals necessary for complications of treatment. So here are the reference we need to look through and then we're heading into radiotherapy. So for assessment rehabilitation it's pretty similar to chemotherapy really and I will highlight that excellent blood sugar inflammation control at minimum is really important and if we do see elevated Hb1c in the pre-diabetic or diabetic range where there's indications clearly of insulin resistance we would want to manage that quickly. And that's, I do find this is where the ketogenic diet, and my version is Mediterranean style anti-inflammatory, that would be considered pre-treatment throughout therapy, because we do find that IGF-1 signalling is involved in radiotherapy resistance. In terms of toxicity, of course there'll be direct tissue damage in the radiation field, and of course there's less damage if we're being precise about it, and we're getting better and better at doing that. and one of the most common side effects is radiation dermatitis and there might be a risk of infection where the tissue is compromised. The breath hold or DIBH, which is deep inspiratory breath hold, is important where it's available locally during radiotherapy because it can reduce heart exposure to radiation on the left when we're treating left-sided breast cancer. We also protect lung and liver on the right. And don't forget there is an increased risk of new malignancy. secondary radiotherapy in the long term. So this is radiation dermatitis in different grades and different severity. You can see from mild to quite severe. The acute radiation dermatitis starts within weeks of starting radiotherapy with severe skin redness and maybe dryness and then there may be some peeling of the skin layers which is where discoloration is and then maybe it's ulceration and the risk of infection. And don't forget that actually just because they're completed treatment doesn't mean they're not going to get radiation dermatitis later. So actually the effects quite often peak two weeks after completing radiotherapy which is why good anti-inflammatory control is so important after you've actually finished it and there will be chronic effects as well. The managing radiation dermatitis usual protocol people be told nothing on the skin two hours before four hours after. You need to make sure people avoid commercial creams that may contain metals and there are various interpretive recommendations. Really the most helpful ones I have to say I do find curcumin useful. We tend to give people curcumin and berberine unless it interacts with other medications during radiotherapy. Vicocream we do use in treatment. There's emerging evidence for EGCG with a great randomised control trial published recently, but it's very difficult to get this concentration in a commercial product. It's quite difficult to stabilise EGCG properly. So at the moment, this has been freshly prepared in the trial all the time, and this is not something that we really can do at the moment. And there's some interesting research around black human seed gel as well, but we don't really know where that's going because it's one study. So clinical experience for me, yes I do give berberine, I do give moderate dose curcumin during treatment and for us in our clinic we have seen no grade 3, grade 4 radiation dermatitis reactions so far, touch wood. So we do find that this is clinically sensible, we do use VicoCream recommended, we also of course tell people the fact that it stains the sheets because it's bright orange and so people might need to be mindful of that. We can use Then the mop-ups for higher dose curcumin, gingham, boswellia, for example, after radiotherapy to mop up inflammation. And I also use, with regard to immune support and overall well-being support, I use saburine, ginseng and astragalus before, during and after radiotherapy quite often. Again, provided it doesn't interact. And usually mushroom therapy will also be continued throughout that. So are there integrative considerations? You might consider phytomelatonin, melatonin. Melatonin does have some clinical evidence around enhancing therapeutic effects and potentially radio protection. Phytomelatonin, yes, we know it exists. We're not really sure whether it's clinically effective though, but I know that from your perspective and your scope of practice, you won't be able to recommend melatonin, but you might be able to refer. And age bolts, there's hyperbaric oxygen therapy. It can be worth considering for referral. Again, what I would do is make sure that they go somewhere where they're aware of cancer and they need to have proper pressure. So MS centres really are where people would go to for that, not recreational kind of age bot centres. Ideally, if someone goes for age bot, they would be in ketosis or be fasted or have had a high fat snack. And if they struggle to get there, you might give them some exogenous ketone esters. There's less evidence for it in breast, I have to say. But certainly for their head and neck cancers, it has been shown to be quite effective. Hypothermia is used in other countries, but less use here in the UK. So post-treatment after radiotherapy, even though it's local radiotherapy, can suppress white cell count. and can have more systemic effects. So you do need to reassess the blood tests four to six weeks after radiotherapy for early kind of recovery, really, and targeting that. And of course, for us, a lot of the time, radiotherapy is the last thing on the line, right? Someone might have had surgery beforehand or even surgery and chemotherapy before that, and radiotherapy might be the last bit. So they would have accumulated quite a bit of burden really through the previous treatment. So you do want to assess them and support them in the early recovery phase as well. And then two to three months after their latest treatment, you might want to reassess other model areas, depending on what's coming up next, really. Nutrition lifestyle optimisation, of course, this should be the core always. There might be some specific consideration around making sure there's good skin care. sun protection, making sure there's mobility in the area, considering scar work and also managing the fact that if someone's had lumpectomy and radiotherapy that whole area of the breast will be quite lumpy and people can get really quite anxious about the lumpiness and whether they see something new. It's well worth getting them used to what their radiotherapy breast feels like and getting them also examined by professionals as needed. So here's some of the references for radiotherapy. Immunotherapy, I just focus on ICIs, which are immune checkpoint inhibitors. So really, mainly for us in the UK, this would be pembrolizumab, used for triple negative breast cancers in particular, and a combination of chemo and immunotherapy, really. That's where most of you will encounter immunotherapy. I'm not talking about the kind of things like HER2 agents. They're more for me in a class of targeted agents, really, and we've discussed those elsewhere. So in terms of assessment rehabilitation, I will make a note on the fact that what I'm talking about here is much more general. And the studies have mainly been done in melanoma, not breast cancer. So we don't know as much about triple negative breast cancer because the indication for immunotherapy is relatively recent. So in general, you still need to kind of, as above for chemotherapy, you really need to make sure that 20 grams plus of fibre daily is an absolute must and no probiotic supplementation. And that's really based on a recent study in melanoma that showed that the best outcomes actually were in the group with not only probiotics, but who were eating sufficient fibre. So always food first in terms of gut microbiome support, which does influence the outcomes of immunotherapy. So a wide variety of vegetable derived fibre, seven to ten portions of rainbow veg daily, 30 diverse plants per week. So making sure people are not eating the same thing and good prebiotic sources. For me, non-bloating polyphenols are really, really important. Deanna Menick has written some fab. things around polyphenols, you can look at this blog and other blogs that she's done. And you might want to consider giving additional kind of polyphenol support for things like Acomancia with aromamia berry, pomegranate, etc. So there are some specific considerations that ideally people who will be undergoing immunotherapy would need to be optimised in terms of not receiving PPIs or antibiotics too close to immunotherapy. And that would, of course, not depend on you, it would be up to the medical team. But also think about their overall risk for having a poorer outcome. Do they have significant risk factors for dysbiosis? Are they really inflamed? Because those two things are going to usually reduce the benefit from immunotherapy, certainly based on melanoma studies. So optimise inflammation and do some gentle food-based GI microbiome support as much as possible. And there's some useful reviews here on the immunotherapy and GI microbiome. interactions. So the side effects I just put in again just a quick reminder the side effects for immune checkpoint inhibitors you will mainly encounter Keytruda and do remember to keep an eye on any symptoms after immunotherapy that may be due to a new autoimmune disease and that can be delayed. People might present during treatment or they might present 6, 9, 12 months after the treatment so do consider family and personal history if they already have. In autoimmune disease, either in the family or personal history, they're much more likely to potentially suffer that as an adverse effect. And in my experience, autoimmune thyroid disease in particular is not uncommon. And some reference for you here for endocrine and targeted therapies, you will need to see the specific breast cancer sections. We've covered those, so I'm not going to go over those again. I hope you have found this lecture and this resource Interesting and useful, and thank you for listening. ________________ 2.3 Cancer and Menopause Management Insights Okay, so we are here to talk about cancer and menopause support, because I think this is a really, really important topic. One in two people are estimated to get a cancer diagnosis at one point in their life. So we're dealing with 50% of the population at some point. And I think that what might work for some people who don't have a background of cancer may or may not work. for others. So it's really important to take this complex topic and really unpick it. So that's just my background, I don't have any disclosures relevant to this presentation in particular. So really what we're aiming to do in this session is to understand and value a different context in which both frank menopause but just menopause people with an cancer diagnosis and those who might have completed their primary cancer treatment. and are then in the survivorship phase. We also talk about different menopause support options available in several different cancer types and I want to focus quite specifically on managing the side effects of hormone therapy or endocrine therapy in breast cancer because there's been a lot of things that have been floating around for example in HRT around breast cancer and I want to be able to look at the data and just highlight a few important things for you to consider. And of course, I want to be able to put the whole menopause conversation in context, because as you well know, it's been dominated by the HRT conversation, and particularly for hormone receptor positive breast cancer, this isn't often an option. So what we really need to do is look broader and see what is the evidence for other support approaches in that particular setting. So as I mentioned, we will be covering the main support options for people with an active cancer diagnosis. survivors with a particular focus on breast cancer. Of course this topic you know I could do a whole day's event on this topic really maybe two days even so it's not meant to be completely exhaustive but I really want to introduce it to some of the things you might be thinking about and I will do a reminder of scope of practice I know you know it but I have to put it there that risk benefit discussions for any medical treatment are out of scope nutritional therapists so whatever your personal opinion is. and whatever your understanding is you do need to refer to a medical professional to have that discussion because it is out of scope to discuss that with your client. I will not be having a lengthy discussion HRT and primary breast cancer risk so that's the risk of the first breast cancer diagnosis and because I'm typically people who've already had the cancer diagnosis. And actually, when we start having that lengthy discussion, you really need to start getting very granular about genetic backgrounds, gene and interactions. So in terms of cancer treatment menopause, if you're already going through a natural menopause, symptoms can be exacerbated by treatment. So if you got a diagnosis of postmenopausal breast cancer, your estrogen levels are already low, of course, so are your progesterone levels. But if you get an aromatase inhibitor. which decreases your estrogen levels even further. On top of that, then you can get your natural menopausal symptoms exacerbated further by that treatment. Now we also have, apart from natural menopause being made worse by certain treatments, we also have iatrogenic menopause. And iatrogenic just means it's actually treatment induced or medical therapy induced. And that's menopause as a result of cancer treatment, which may be surgical or medical or reversible and irreversible. So in surgical menopause, really talking about the removal that will be producing the oestrogen and progesterone within the productive period of the woman's life. And this normally happens during abdominal pelvic surgery, various gynecological cancers, also colorectal cancer quite often, and also in reducing genetic syndrome. So that's BRCA1, BRCA2 genetic syndrome reduction surgeries. also used in Lynch syndrome. It's just a few examples. So of course, surgical menopause is irreversible. At that point, you're not going to be able to regain that function. Medical menopause, ovarian suppression with injectable drugs. So this is Zolidex as an example, can put people really rapidly into medical menopause, but depending on your menopausal status, it may or may not be reversible. Also starting chemotherapy. radiotherapy and hormone therapy may also lead into menopause if you're in the perimenopausal age. So it's important to realize that menopause may be irreversible so where your perimenopause you push over the edge into your menopause because of treatment the surgical intervention that's very relevant for women who have been diagnosed with breast cancer or the cancers in around 40s because actually chemotherapy and radiotherapy that age they're quite you know your physiology is quite vulnerable at that point already and they may be reversible so for younger women with non-hormone dependent cancers they're quite often given ovarian suppressions such as zolidex injectables or something similar to try and effectively protect their ovaries from chemotherapy related damage now the evidence on this is it can be a little bit shaky but just to make sure that we are trying to shut the ovarian function down women might go on this even if they don't have a hormone dependent cancer and then their their ovarian function will then potentially restart with after completion of that treatment and cessation of the injectable medication. So I can tell you I have personal experience of that because I had a personal experience of a breast cancer diagnosis that's HER2 positive at age 33 so I was put into rapid medical menopause with Zolidex and then my natural cycles came back because I didn't have a hormone receptor positive cancer. So it can happen very quickly, particularly if you're younger, it can come as a bit of a shock. But there's a lot we can do to support women through that. So in terms of menopausal symptoms, of course, you will have seen these at some point through the day. But as you know, it will impact anything from head to toe, from the central nervous system to skin changes. metabolic changes, sexual health, urogenital system, the musculoskeletal system. And it's important to realize that sometimes these symptoms in people who have had a cancer diagnosis may be genuinely menopause related, but for some women, some of these symptoms turn up on hormone medications such as tamoxifen, even if they're not menopausal truly. So it's important there may be medication or menopause related. Options for symptom management, of course, there's many specific cancer cases where there's neutral risk or favorable risk benefit. And there are cancers for which the studies show there may be some benefit in giving HRT. And that's colorectal cancer, for example, and HCC, which is a liver cancer. cancer. And of course, non-HRT options as well as various medications we'll go through. Nutrition lifestyle, of course, this is what we hear about, which is really, really important, foundational in everything that we do. Psycho-emotional support is really, really important for people going through cancer as well as going through those menopausal symptoms. And that might include psychosexual support, CBT, mindfulness-based interventions. and complementary medicine modalities that you might want to put together into your overall plan. So acupuncture, yoga, herbal medicine and many more. And I'm not going to discuss herbal medicine in any great detail in this talk because to be honest, there's just far too much to cover. With acupuncture, I think it's really important to be aware of the fact there's a difference between traditional Chinese medicine acupuncture and medical acupuncture. So medical acupuncture training is done by associations such as BMAS and quite often medical doctors, physiotherapists, musculoskeletal professionals such as chiropractors, osteopaths will use that as a modality to manage pain and it is very useful for pain management but it will not cover other symptoms. Whereas traditional Chinese medicine acupuncture usually again back so British Association, British Acupuncture Council actually. will register both TCM and medical acupuncturists. So with the TCM acupuncture, you're looking at the whole person's physiology. So when you're looking at regulating things like the hot flushes and night sweats and overall supporting someone through cancer treatment, really TCM acupuncture is the one you would use because you're not just looking at purely at pain management. So it's important if you are asking acupuncture. to work alongside the nutritional lifestyle work that you are doing with them, that you understand what you are referring for. So it is important to be aware of the differences. And symptom management in terms of menopausal symptoms is important, but it must be built on the whole person foundation. And really, this is what I focus on when we look at systems approach to cancer, which is my cancer training, is that we are looking at the whole context, all the different systems, we're looking at the whole health timeline. We're looking at the predisposing factors, precipitating factors, and anything that might be a problem at that moment. So we are putting this, it is just an add-on. It is not a replacement for all of it done properly for those who are going through cancer treatment or cancer survivors. And do remember that cancer care is a team affair. We know that a lot of our clients will have their multidisciplinary care team in the NHS. But to me, that... Thank you. extended team needs to really extend to us as nutritional therapists and anybody else who's involved in the person's care such as acupuncturist or osteopath or whatever it is that they are receiving we need to make sure that we are all working together and managing cd and persistent symptoms may require more than just doing nutrition lifestyle this is foundational but it might not be effective enough in all cases and it isn't that you've done something or you haven't been effective enough is just that cancer is complicated endocrine therapy affects so many different systems in the body as well as chemotherapy and other therapy modalities so you need a team so do build your professional network for some of the modalities i will mention from the integrative perspective because it does benefit your clients and you can also generate cross referrals that way so i'm going to talk a little bit about estrogen receptor positive breast cancer as an example of the treatment, how it impacts menopausal symptoms and how we can support people. So where you can get an oestrogen receptor positive is mainly treatments. So quite often women will get either a mastectomy depending on their presentation or a lumpectomy or WLE with radiotherapy quite often. So that's the two kind of surgical choices, plus or minus radiotherapy. they will be put on endocrine therapy. So that's looking at tamoxifen usually in the premenopausal stage and postmenopausally we're looking at mostly aromatase inhibitors. And I will go over some of these different drugs and what they do. Now there may be different combinations. You might find that if you're working with people with a cancer diagnosis, you might find that you will see different things such as in younger women They might use a Zolidex combination with Letrozole, for example. They might use Zolidex alone if they're not actually hormone sensitive, but they have triple negative and they're younger or they have a HER2 positive and they're younger. So there's kind of there's different combinations you might see, but usually tamoxifen for premenopausal, aromatase inhibitors for postmenopausal. Advanced disease, there are usually other medications such as chemotherapy, and usually any endocrine options such as aromatase inhibitors will be really used alongside it. And there's additional options that we use such as injectable therapies such as falvestrant to add to our normal armamentarium for this particular thing. So you can see the number of different ways of blocking oestrogen receptor. signaling in terms of the estrogen receptor positive breast cancer. Tamoxifen, so this is kind of the bane of our lives in terms of interactions if you're working with breast cancer. And the mechanism of action of tamoxifen is that it's a selective estrogen receptor modulator or a CIRM. Now, what does it actually mean? It means that sometimes it can be an antagonist and sometimes it might be an antagonist. receptors in different tissues. So it's an antagonist, which is why we use it to block normal oestrogen receptor signaling in oestrogen receptor positive breast cancer. However, it is not an antagonist for oestrogen receptors in the endometrium. And actually, it carries in increased risk of endometrial cancer with its use. So any abnormal vaginal bleeding on tamoxifen needs to be investigated really promptly. Tamoxifen is a weird word. drug because tamoxifen is not actually the active drug. In doxephen, its metabolite, you can see at the bottom of the slide there, is the actual primary active metabolite. And to get us from tamoxifen, which is a precursor to the active endoxephen, we need to jump through two different CYP stages. And you can see the two main enzymes involved are CYP3A45 and CYP2D6. Now, there are other CYP isoforms also involved, but they're the main steps. And so we'd want to make sure that if we are supporting someone on tamoxifen therapy, we're really avoiding any inhibitors of this conversion, because at that point, we would be worried about not reaching target endoxifen levels. And I know a lot of us are used to using the natural medicines database. And if you actually put it in for a CYP2D6 interaction, sometimes it will go. there's a risk of increased side effects because you'd get more active drug. Well, Tamoxifen actually is not the active drug. So the C6 inhibitors won't increase, it might increase your Tamoxifen levels, yes, but that won't result in more side effects. It will result in a reduced efficacy because we're not getting through those steps to get to Endoxifen. So please be really careful with Tamoxifen. It does interact with a number of different things. and you don't want to be inhibiting the conversion to the active drug. High dose curcumin should not be supplemented when you are on tamoxifen. It doesn't mean high dose curcumin has been shown in a human clinical trial to reduce active endoxifen levels. So that's really important. Fulvestrant is a drug that many people might not have heard of and the mechanism of action is an oestrogen receptor degrader. It basically binds to the oestrogen receptor and targeted for degradation in the cell so that means the estrogen can therefore risk to bind to effectively. It's quite slow acting and usually it's combined with other therapies so depending on the menopausal status it might be given with zolidex or various other anti-cancer drugs and the main side effects of fulvestrant are menopausal symptoms as we've seen before but also can elevate liver enzymes, nausea, fatigue, rashes and musculoskeletal pain. Aromatase inhibitors are much more common. You will see a lot of postmenopausal breast cancer patients on those. So once we've actually tipped over after a year, after our last period, that aromatase is our main source of estrogen, unlike the aromatase in more like the fat tissue. rather than our normal aromatization that used to happen in the ovaries, because of course the ovaries aren't working anymore. So from our perspective, we need to be really looking at the adipose tissue. And that's why postmenopausal weight gain is actually a risk factor for breast obese and overweight BMI after menopause is associated with increased risk. So it's really important. Weight control is really, really important. and astrazol, letrozole and eczemestane are those aromatase inhibitors so we are really aiming to target that last step we're not trying to block the oestrogen from binding we're trying to really block the androgen to oestrogen conversion with an aromatase inhibitor and as i said it's mainly in other tissues it's of course not they said that blocking in terms of side effects they do have all the typical side effects which we'll go over but the brand really does matter in terms of side effects so your client might wish to speak to their pharmacist or a doctor to see if there are any other options. So sometimes switching between the side effects. I am going to come back to this obesity or overweight and think that visceral adiposity, most of you, of course, are very well aware that it's a metabolically active tissue. And there are multiple different mechanisms, particularly that adipose-driven inflammation, immune dysregulation, that can play a part in both initiation and progression of breast cancer. it's really important to remember that we do need to try and gently and compassionately manage people's BMI. So some of the side effects of endocrine therapy, both aromatase inhibitors and tamoxifen have all the usual menopausal symptoms on their list, so sleep, vagina dryness, loss of sexual interest and all the things that I've shown you before. Tamoxifen predominantly tends to cause more hot flashes, it can affect mood, so depression, it has a significantly increased risk of... clots and that's DVT which is a clot in the lung oh sorry DVT which is caught in the leg and PE which is a clot in the lungs so it's really important again that you while of course you're not going to be diagnosing any of this if someone on tamoxifen comes to you and they say I've got a swollen leg and I've just been on a long haul flight or I've just got a swollen leg and I've been immobilized after surgery or whatever it is unilateral calf swelling in particular you need to get them to go to A&E as soon as possible. So we do need to watch out for clots, it's everybody's job to watch out for things that are unusual in cancer patients and get them investigated really quickly. Metrial cancer, so we're kind of decreasing the breast cancer risk and increasing them. And so usually we would want to look at family history. We would want to look at family history, make sure there's no endometrial cancer family history, but also any unusual bleeding absolutely required. I think if you know whether you are an ant cancer specialist, if someone's had a history of any kind of tears and they're presenting with new, unusual, persistent symptoms, they need to go and see their GP as promptly as possible. That's just my rule for things. because it's better to check it out and be told it's all fine than sit on it for a few months and find out it's a bit too late. So with aromatase inhibitors that are mainly used in our postmenopausal patients, we are looking at particularly decrease in bone mineral density. Hence, because, of course, we are getting increased risk of osteopenia, osteoporosis and osteoporotic fractures. We're also seeing a big bump in the MSK symptoms, and that's joints and muscle pains. And you might see in literature, if you look at it, they're called AIA, and that's called aromatase inhibitor-induced arthralgia. Basically means pains and aches because you take eletrozole and astrozole. Really debilitating for patients. You know, menopause itself would come with some MSK symptoms. quite often and then on top of that you're now getting extra symptoms from the medication and suddenly people who are really active who are really used to getting out and about are really debilitated by symptoms so it is really really important to address. One role we can definitely play within managing aromatase inhibitor side disease risk because it comes with a significantly increased risk of myosin and gyna. we really want to assess and optimize cardiovascular risk long-term and the final bit is ovarian suppression with something like Zolidane and this is one brand there's other brands out there but this will give menopause all the associated symptoms so you don't get kind of the luxury of going through within a couple of months you are full and within medical menopause So in terms of the impact of those side effects, it's of course a massive impact on the quality of life of women who are having to go through this treatment. But it's also a significant problem for women who then have to discontinue treatment because the side effects are so bad. And those rates are very, very high, where early discontinuation of tamoxifenol... five sometimes and at five years you can see anything up to you know 31 to 73 percent of women no longer being on these drugs because the side effects are so bad now this is because they're not being managed as well but remember these rates are not really providing integrative support not providing any usually advice on how to manage those symptoms you The problem with discontinuing these treatments early is that evidence is very clear that discontinuing this treatment early without any additional support increases the risk of recurrence and decreases survival in these women. So symptom management is absolutely essential to enable better tolerance for people. So what I'm going to do now, this is just kind of a general quick gander through the different estrogen receptor positive breast cancer. related treatment options and now I'm going to really look at specific groups of symptoms and what we can do about them what can we recommend to our clients and how can we engage with everything that they're going through and you will generally find that there will be people who will do absolutely fine and they will do terribly on another medication everybody's very different and different individuals you And of course, it's a matter of the whole gene environment interactions in terms of guiding. So looking at the vasomotor symptoms or VMS, that's what usually we search for when we look at it in literature. And these are things like hot flushes and night sweats usually. So there are various relatively nasty conventional drugs. So antidepressants such as venlafaxine, which is quite hard to get off of. gabapentin which is quite a sedating neuropathic pain medication clonidine all of these come with significant side effects of bone so i always think that to me personally and that's my opinion we need to be trying everything else apart from doing extra drugs for people weight management is important and again we talked about how obesity in general creates that environment where we have effectively increased risk of increased estradiol levels already because we've got more aromatase churning out postmenopausal estradiol but also we've got all of those adipokines right that are then circulating around and if you know a little bit about cancer you know inflammation and tumor promoting inflammation is one of the hallmarks of cancer so we'd want to minimize that as much as possible And so weight gain is associated with increased risk of developing hot flushes and night sweats. And so we want to try and aim for a 10% weight loss or return to normal BMI depending on where the person is at and to see if that will reduce symptoms. Be effective and it's not recommended for use in supplemental form in women with hormone receptor positive breast cancer because we haven't established good safety. Eating normal organic unprocessed soy. is absolutely fine. There's no evidence that that's going to be harmful. Looking at other non-pharmacology you will see that on the slides you'll see a whole list of references. If you're working within this, so CBT is one of those things that again we can get referred for on the NHS and that has been shown to reduce menopausal symptoms and the impact of hot flushes and night sweats. Hypnosis and medical hypnosis shows an effect and there are two randomized control trials on that and yoga and acupuncture can also have an impact on the frequency of having those hot flushes and night sweats and potentially their burden. So acupuncture has actually been recommended by the joint ASCO-SAO guidelines in breast cancer for that particular indication and there was interestingly one randomized control trial. This shows that acupuncture might have equivalent efficacy to one of the common antidepressants used in the setting called venlafaxine. So these are certainly things you'd want to have up your sleeve because I have to say, people ask me, how can we manage it nutritionally? And I'll just say that nutritional interventions are really good at supporting the individual, really good at getting that weight management under control. but they can't always do everything. When someone has really severe symptoms, we need multimodal interventions. We need more than one thing to be able to get on top of them. So in terms of aromatase inhibitors, as I mentioned, they come with a lot of aches and pains and stiffness. So from the conventional side on the NHS, you might get things like and an impact on the gut side of things or other pain medications. So, of course, opiates we know will have an impact on constipation and other problems. So we want to, again, try and minimize medication use unless it's absolutely necessary. And there was a network meta-analysis in 2018 that showed that acupuncture, aerobic exercise and opiates might have significantly improved pain severity scores. I will caveat that and say that omega-3 is particularly in people with obesity rather than just generally for all people with aromatase inhibitors. Acupuncture, there's a recent meta analysis of seven trials showed that it was safe and effective treatment for those aches and pains in women using aromatase inhibitors and the recent joint guideline by SAO and ASCO for pain and pain. strongly recommends acupuncture for this indication. It's actually the strongest recommendation in the guideline. And you can go to the SAO website and find their guidelines page and you'll be able to read those recommendations on pain. So having an acupuncturist in your pocket who you have a really good relationship with and you can cross-refer with is really really useful. So physical activity is also really essential. Again, that's something we can absolutely counsel people on in terms of saying you really need to make sure you're getting enough physical activity. And the meta-analysis showed that exercise relieves those symptoms really significantly. And of course, it also improves overall quality of life and it might improve sleep and it reduces the risk of breast cancer occurrence. So physical activity is a wonderful... pan-intervention that can impact so many things for people. Now I will caveat it and say that if you're asking people to increase physical activity it's really important that we don't send women who've undergone surgery or gym. So there is a risk of lymphedema which is the swelling of the arm or the breast depending on what's relevant if there are lymph nodes removed so underarm lymph nodes or auxiliary lymph nodes. So that means that there are certain exercises and certain static codes that are not indicated. So we do need to guide, particularly resistance training, particularly anything to do with the upper body. So the NHS, they might have an access to a physiotherapist. And I know not everybody does, but it's certainly worth considering. And there's cancer exercise specialists. You might look at CanRehab Trust. People can self-refer to get contact details locally. Or you might look for a cancer exercise specialist that's level four trained locally to you. And yoga therapists as well. So again, there will be people who are trained to that can cope with the complexity of having someone who's undergone multiple interventions in their treatment. And so, you know, surgery. as well as maybe radiotherapy, for example, they might have other complex needs. They might have had other problems, you know, other back pain or other injuries that need to be taken into account. So, yeah, while we know that there are certain things they can do very safely, most people can do get out and do walking safely, resistance training needs some further guidance. And don't forget to talk to people about the three legs of the stool. So we normally talk about. Aerobic, resistance training and flexibility are the three legs on which you need to put your physical activity. And as we get older, we need to add a fourth leg of the stool because we get a bit wobblier and we need balance training. So physical activity is important to explain to your clients. It's not just cardio or it's not just resistance. It needs to be a balanced regime. It needs to be a same balanced regime. So think about supplementation, vitamin D alone, just giving it relatively randomly in trials, unsurprisingly, may not be effective. But raising vitamin D from being deficient, so under 75 to 100 to 165 has been shown to reduce the score. So that's an intervention we would do. And of course, we would normally give D3 and K2 together. And we'd also want to make sure that normal calcium and magnesium levels are in place. Omega-3, as I mentioned, mainly the neuromatase inhibitors. Glucosamine, chondroitin, again, it's just one study really showing moderate improvements in those symptoms, but certainly isn't going to be, you know, might be helpful for people. And there are different combined interventions with a single trial. OK, so it's important to know that there are single trial interventions and we really need more data. So one of them was. Pure Veda, which combined hydroxy tyrosol from olive oil. omega-3 fats and curcumin and that's been shown to reduce CRP and pain. POMETEE has also been studied so that's Professor Robert Thomas's favorite and there was a formula from Chinese herbal medicine that was also shown to have a significant improvement in symptoms. But of course you do not want people getting Chinese herbal medicine online because it's very dangerous to do so and it needs to be done by a registered TCM practitioner. Apart from all of those aches and pains and the hot flushes and night sweats, we're also now entering the bone loss, which is, of course, the subject of you's presentation earlier. And I'm going to cover just some basics here as relevant to people who've had a cancer diagnosis. So we know that osteoporosis risk related to hormone therapy can be modified by different SNPs. So some specific CYP17A1 and VDI and ESR1 SNPs. they have been linked to worsening osteoporosis, worsening bone loss when you go on to a neuromatase inhibitor. But we don't at the moment have a really good composite score that we can send people for and say, okay, well, this is going to be bone loss. So of course, you might have been familiar with DEXA scans that are used to check for osteopenia osteoporosis, they're medically requested scans usually. And most women who have had a history of breast cancer and who are on an aromatase will be off treatment to try and prevent the process. So we know the fractures, so quite often medically there will be offered drugs to try and help that. So bisphosphonates, so this is your oligodendronic acid as an example, or dinosumab. mainly in advanced cancer patients, they might be offered those. And there is some evidence that it can reduce recurrences in and outside bone in specific patient populations. So it's very much case dependent, the medical decision as to what the pros and cons of using those drugs are. Now it's really important because of the risk of a really severe complication called osteonecrosis of the jaw that that women are sent for dental checkups before they start any of those kinds of treatments, because if someone has to do have dental surgery afterwards, they're at risk of this really significant complication. It's really rare, but when it does happen, it can be catastrophic. So dental health checks are really, really important. And of course, we know the medical guidelines suggest supplementing calcium and vitamin D if you get a T score of under two, minus two. In terms of general bone support I already mentioned I'm sure that I haven't been there for the beginning of you this presentation but I'm sure we all know about the calcium D3K2 magnesium as well as some of the other micronutrients playing a role. Please do remember to counsel women around smoking and alcohol of course that's going to have an impact on their overall cancer risk and you should mention it to them with regard to bone health because both of those increase risk of osteoporosis as well. And of course, use it or lose it. So you can take calcium D3K2 magnesium and bisphosphonates until the cows come home. But if you're not moving, you're not going to be able to slow down that bone loss. So weight bearing exercise is absolutely essential. I sometimes say that you wouldn't expect to eat tons of protein and expect to grow big muscles. Well, When we're taking Adcal D3 and sitting on the sofa and expecting it to have an impact on our bone density, it's exactly the same thing. So it's really important that we move and that it is weight bearing. So it might by itself, of course, exercise. We're not sure how much it impacts people because we haven't done good comparative trials and it will depend on the age, risk factors, and what is your baseline bone density before you even went into treatment. But it is important, whatever you do, that physical activity is absolutely on the plan for anybody with a cancer diagnosis to whatever degree they're able to do it. Certain devices might be considered so they're not studied specifically in cancer but they're low intensity vibration devices such as LiveMD for example and you can get some information on those on the Royal Osteoporosis Society website so definitely worth going there to see. In terms of other side effects, so we've gone over the hot flashes or the vasomotor symptoms, we looked at the aromatase inhibitors causing trouble in terms of aches and pains and bone loss, so sleep disturbance after those is one of the other really really common side effects. that people complain of and of course if we're not resting properly we're going to have trouble with our own resilience and we're going to have trouble getting through treatment anyway. So CBT-I is a cognitive behavioral therapy for insomnia and sleepier app is now available free so you can refer away for that. Physical activity again we talked about it's going to come up and I know it's not nutrition but it's really important that we consider that in the overall and there's been RCTs in various exercise forms and showing benefit for sleep scores. Acupuncture or auricular acupuncture which is what AA stands for, there's been multiple studies showing significant benefit and there was a really recent randomized control trial with moxapine treatment showing that acupuncture not only mental and emotional symptoms which of course is really really important to manage. Melatonin, there was an RCT with three milligrams of melatonin, again it's not a panacea for sleep but it can be helpful in some people and it has been licensed for short-term use in over 55s on the NHS. So general sleep advice of course all the general things that we'd normally give, it's not been studied formally and cancer patients or people who have gone into the survivorship phase So this is clinical experience, but we might as well use other supportive care as well, because ultimately there's very little risk and there might be some potential benefit. And if you are going to be working with people who have a cancer diagnosis, then it's really important, of course, that you are meticulous about checking your interactions and that you advise your clients to always contact you if anything changes, because people just sometimes don't think it's going to be a relevant thing to do. So sleep complaints are so common, they exceed half of the patients who are using aromatase inhibitors. So it's really important that we know and manage these symptoms. And what's been really interesting in literature is we are seeing there's a triad of symptoms. So arthralgia, which is aches and pains, fatigue, and insomnia that are correlated to this. So the question is, and I can't answer that question, but I'm pretty sure the answer is yes, but I can't give you a file on it. Could managing inflammation without a nutrition lifestyle toolkit help this triad of patients? So monitoring people's inflammatory markers and normalizing them is certainly a priority anyway. And then we can see, does it lead to better clinical outcomes? And that's when we need a good, well-designed trial to answer that question. So other things that people come and talk to you about is vaginal symptoms. So then they, of course, will. from things anything from burning and discomfort to problems with sexual health and it's important to realize of course the sexual health quite often is treated as just this is the symptoms we just have valve vaginal symptoms that's why we've got problems with sex but when you've gone through cancer treatment there are a number of other things that you have to be dealing with you're dealing with stress you're dealing with a new body you didn't sign up for um and the number of other things that are really really important to address so psychosexual therapy you or relationship input can be really important. So don't do it just because they're having physical symptoms, you definitely need to refer for other things. So CBT we've already discussed, vaginal moisturizers, lubricants should be the first port of call. And it's really important that vaginal moisturizers are used daily to help relieve symptoms. So lubricants are used as needed for sex, but actually vaginal moisturizers have to be used daily. And in my mind, doctors who prescribe baromatase inhibitors or tamoxifen should be prescribing this kind of product alongside straight away because the longer it goes on the worse it gets and the harder it is to get symptom control. So yes products are available in the NHS so do empower your client to ask about them and you can see the link here. There's been some other trials of vitamin D or E suppositories and there's a small RCT showing that might have been some difference for people's available. And I'll talk a little bit about the hormonal options. It might be an option in some patients. Again, it's really discussion between oncology. So HRT and cancer moving kind of away from symptom management, think about, okay, HRT and cancer, you know, seeing lots of really interesting headlines from various people saying HRT is safe for breast cancer patients. Well, as usual, the whole picture is much... much, much more complicated. And don't forget to also tune in your radar for commercial interest within that as well. Risk benefits of HR stages. So really, this is where describing, it needs to be able to know the evidence and assess someone individually. So systemic HRT, which is HRT given either orally or transdermally, not vaginal HRT options, they might have a favourable risk benefit for things like colorectal cancer, for example, has been associated with better survival, might have some neutral benefits in terms of cervical cancer, it appears to be risk neutral. And in the guidelines, what... whatever people say to you, all the medical guidelines are currently available. Say the HRT, systemic HRT is contraindicated for oestrogen receptor positive breast cancer. And I'm going to go through a little bit about why. But just again, do remember that you shouldn't really be using this in discussion with your clients because it's out of scope. So there is. there's been a lot of things being flung about with old trials from like the 60s or the 70s. So you've got to remember that all data is not truly applicable because the standard of care of how we treat breast cancer changes over time. And there's problems with using observational trials because they have significant limitation and HRT is medication. The randomized control trial is the gold standard. It might not be applicable to our nutritional lifestyle complex intervention very well, but it is absolutely the gold standard for HRT. And currently, there is absolutely not a single randomized control trial in HRT and estrogen receptor positive breast cancer showing no increased risk of recurrence, no increases in mortality. OK, there isn't one. And therefore, anybody who says something is safe based on observational trial, they're not actually following the medical standard of care. Now there is a slight wobble effectively around where you have a non-hormone driven breast cancer and there are some suggestions in the data the HRT might potentially be neutral but there's insufficient data and in one triple negative breast cancer study recovering your cycles and having higher estradiol levels was linked to worse prognosis but we just don't know. We don't know enough and the likelihood is it will depend on the patient. the person's genetics, the person's environmental exposure, and the tumor environment, the tumor genetics as well. And do remember that just because someone's had a one kind of cancer first, if they are due to recur, they may or may not carry the same receptors. So looking at the HRT in estrogen receptor positive breast cancer patients, you can see that there was a meta-analysis of different studies. And you can see again the limitation of observational studies. They're studies that just bunch a whole load of people together and kind of try and associate it with recurrence and mortality. But when you look at RCTs, which is what we used to do standard of care in medicine, is it has demonstrated increased risk of recurrence in postmenopausal patients. Although apparently no significant mortality impact. However, for some. not want to have an increased risk of recurrence of 46%. So there was another more recent review meta-analysis which again very much shows very similar data. It's increased risk of breast cancer recurrence and it's significantly weighted to those with hormone receptor positive disease. So oestrogen receptor positive breast cancer and HRT, there is currently no randomized control trial evidence that it is safe. And actually, it shows significantly increased risk of recurrence. Mortality is another thing. But to be honest, most women I know who've had a breast cancer diagnosis definitely do not have increased risk of recurrence, even if they might not die from their breast cancer. So these are the three trials that have been used. The most commonly used habits, Stockholm and Liberate, HRs, anything over one increased risk. So you can see significantly increased risk of recurrence. And while there's absolutely various critiques of these trials, they're not perfect in any way, shape or form. This is what we currently have base evidence on. And the other thing I would just like to mention that what most HRT proponents who don't work in cancer completely forget is actually there's now evidence that more ovarian function suppression, lower estradiol levels and keeping people as low as possible in people with high risk disease. actually shows improved disease-free survival and potentially later on we might see overall survival as well. So oncology context is moving towards actually more ovarian suppression which unfortunately also means more symptoms for our breast cancer patients but the HRT world has gone slightly mad and decided that we're going to ignore. randomized control trial evidence. So the other thing to mention is that systemic HRT and local HRT and vaginal HRTs are not the same and hopefully you'll get bigger talk about over these couple of days but various prescribers will be considering different factors. You can see it's much more complicated than saying yes or no. It's saying what are the pros and what are the cons for the person in front of me with their cancer and with their symptoms. and non-hormonal options should always come first. So it doesn't mean it's not an option. Quite often in people who have really early disease which is low grade, no lymph node involvement, and now tamoxifen, we might be able to use some low dose vaginal therapies if their symptoms are particularly severe and they failed all non-hormonal options. But again it's a prescriber patient discussion. I'm just going to quickly highlight, as I said, that observational studies are not the same as randomized control trial evidence and that's what we look to in medications. So therefore, using clinical decision making because here in cancer, getting risk benefit wrong has a profound impact. It isn't just increasing your side effects or decreasing your side effects. And the RCT evidence shows us there's an increased risk of recurrence with HRT use in breast cancer survivors, which is likely just because of the hormone receptor positive subgroup. And we need really longer term studies to evaluate mortality risk and late recurrences, because for oestrogen receptor positive breast cancer, recurrence risk can be 20 years plus sometimes. So it's quite a really, really long timeline. And as I mentioned, please don't discuss the pros and cons of this. It should be managed between the patient and the oncologist. We do want to continually re-evaluate this picture and actually I would really like to see complex evaluations that include polygenic SNP influence, so polygenic risk scores, that can be as well as tumor data and patient data to be able to actually accurately precision risk in the future but we need to do a lot more work on that and of course there's so much more that we can do. So I'll quickly summarize and then we'll have a few minutes for questions. As I discussed, cancer treatment may induce or worsen menopausal symptoms or actually can cause someone's menopause to come either early or to persistently stay and it may or may not be reversible depending on particular intervention. So if you're younger and if you're receiving things like caverian suppression, you may be able to recover your cycles but most perimenopausal women would usually go into menopause during cancer treatment. Managing CV and persistent require collaborative multi-disciplinary team so all of the input together and that symptom management needs to be placed in the whole person's or systems context and here's a quick summary of all the different interventions you might consider that are for specific symptoms and please remember that you do want to use the whole toolkit of course the self-perspective but it is important to keep the book to other interventions and other referrals claustrophile networks. And here are some various professional associations, potential resources you might consider. And again it's not an exhaustive list, it's just for a few modalities I've already mentioned and I hope that's been helpful. There's various different references available for you. Oh Nina that was amazing, thank you so much. Very very very inspiring and excellent, brilliant. But time for a few questions. I'm just gonna have a look online. We've been gathering all of the questions on a kind of joint sharing Google Doc. So from the top, would CoQ10 help with the side effects from statins? Was a question from Victoria Bell. There's no... Unfortunately, at the moment, there's not been any good trials on CoQ10 and aromatase inhibitor arthralgias, unfortunately. OK. Are there any genetic tests which can be used to determine what medications may be better for an individual? So cover this a bit later on. Yeah. So there is there are some pharmacogenomic tools that we've got. They are far from perfect, though. And so what I would say. but we are really in the early stages of precision health which is where my interest lies and we need to accumulate a lot more data on people so what we want to be able to do is have lots and lots of data and all the different individuals and have hundreds and thousands of people to be able to really precisely predict your personal risk so at the moment we can use various pharmacogenomic tools and I do use them in my but it does require good and our literature to be able to then say to you, okay, I think based on these, you might be better off doing X, Y, and Z. But medication choice just doesn't just depend on your genetics. Okay. It depends on what's going on with your tumor. What kind of risk are you? What's going on with your symptoms? What is your individual tolerance of that therapy beyond just genetics? So it's a really complicated question. That's why I really want you all to turn on your BS radar when people try and make it really simple. it's a yes or a no and most people who know me will say I'm the annoying person say it depends but I say it for a really good reason of course yes um so we're moving on from that so you talked about yoga as a way to um manage symptoms do you other yoga or is it generally yoga so for breast cancer survivors I would want to make sure that depending on where you are at your state you would want to refer to someone who's definitely had cancer training. So if you go to a general yoga class, you'd have a 200-hour trained teacher who knows usually nothing about cancer unless they've done further studies, right? And that's not a safe environment for most breast cancer patients to be, for example. So at minimum, you'd need to ask them to go to a class with someone who had additional cancer training. And I know Vicky Fox, for example, runs some of the trainings, a number of different organizations that run yoga for cancer. trainings. For people who are really quite complicated, have metastatic disease, who have really bad symptoms, who require a lot of support, I usually suggest one-to-one yoga therapy. And again, I know it's not accessible to everybody, but a yoga therapy, I'm currently training as a yoga therapist. So you're looking at really 800 or more hours of training, okay, for various medical conditions, which means you have, that's a very different level of training to 200 hours of how. yoga so it will include cycle support sleep support relaxation as well as the asana which is the physical practices so depending on what the needs are what the client's budget is i think you might consider different things and you you will see in the link on the slides which i know will be distributed later there are links to people who do yoga for cancer classes you and so one of the most popular ones is Vicky Fox's yoga for cancer it's free online you can go onto her website and she does it to the baseline that would be safe for most people so it's a nice general supportive class. Brilliant excellent okay and then Kate Swain asked why is Amiga 3 more obese? Yeah, good question. I would like Kate to answer that question herself. What did I tell you about obese patients? What do we think? Well, so she says that it's because of increased inflammatory cytokines. Yeah, yeah, yeah, exactly. Exactly. And I think this is really important because this is why we want to do individualized support for people. We're not just throwing a generic toolbox. We want to be able to assess someone, say, actually, in your case, weight loss and anti-inflammatory control. be better than for someone whose normal weight and exercise regime has a normal CRP and ESR, for example. So individualizing it is really important. ________________ 2.4 Comprehensive Cancer Rehabilitation and Support Hello and welcome back to the Systems Approach to Cancer programme and today we'll be talking about rehabilitation surgery support. You've already received a lecture that covers troubleshooting common problems during treatment so there will be some repetition here but I'm hoping it will reinforce the learning points and we'll dive in a little bit deeper into rehabilitation. You also have some additional reading if you're particularly interested in this area. So just as a quick remind again What are our aims around conventional therapy? Well, we want to optimise the client's health prior to any treatment to reduce the risk of complications and support their recovery after the intervention. That's called prehabilitation. We want to try and reduce the risk of and help manage the side effects and support better treatment outcomes by supporting the overall resilience and well-being of our client. And ideally, where possible, synergising with the chosen treatment modality that comes from the oncology team. And we also might have different aims for primary and secondary cancer. In terms of primary cancer, we would want to also support recovery after the active treatment and help manage the risk of recurrence as well as fear of recurrence for those patients and clients. And in secondary cancer, we want to try and support the best quality and quantity of life and that resilience that they really need through the different treatment cycles and the ups and downs of therapy. or low-dose continuous therapy that people might be on. So general principles, again, it's a reminder, I know you've seen it before, but nutrition and lifestyle first, always. And if you are going to use supplementation, it needs to be really targeted at supporting the current stage of treatments, any side effects someone might be experiencing, and optimising this when we're targeting the core systems approach to cancer matrix areas. And we will talk a little bit about the model itself in the later. lectures in modules three and four. So do review and revise your plan regularly. It's not meant to be this is your plan and we're going to leave it. It needs to be dynamic and it needs to be adjusted to how the person is feeling, their biomarkers or what their blood tests are doing or other tests you're running and how their treatment might change from say surgery, chemotherapy, radiotherapy. You need to be evaluating and adjusting dynamically journeying with the person. and if in doubt leave it out more is definitely not better and you will see a sub-population of clients who will come to you with a list of 20 odd supplements various off-label drugs etc but actually a lot of them are not feeling particularly well and some of them might be progressing really quickly too so really we need to be opting for a targeted and personalized supportive approach that takes the whole picture into account And do always check interactions thoroughly. You have a separate lecture on that in terms of various ways that things can interact with each other and how to make your decisions based on what you find in the Natural Medicines Database on PubMed. Do document what you find and make sure that you are asking the person to talk to their clinical team about what they're taking. It's up to them to do that. Most people may or may not want to do it but you do need to document that you were upfront, that you're sharing information where possible. And obviously, There will be times where the person does not want to share that information. That's fine. It's up to them. If you are going to be writing to the medics and the client is keen for you to do so to explain your management, it's really important to keep that communication brief and to the point, really well supported by evidence. If you're going to be talking about any supplements you've suggested, you need to give a really clear rationale that's evidence informed and you need to make it very clear that you've checked the interactions. And really, in your letters, I would very much make sure that they understand that you know your scope of practice. You need to say that you're optimising the client's health overall, supporting their overall wellbeing during treatment, so that they're really clear that you know that you're not treating their cancer, you are supporting the person themselves. And do ensure that on your website and your paperwork, you really have a very clear disclaimer with regard to the Cancer Act. because it is important that we stick within the scope of practice and that nobody's under the impression that nutritional therapy claims to cure cancer. So prehabilitation is really the practice of trying to improve a patient's functional capacity before surgery usually, although to be honest, prehabilitation applies equally to chemotherapy and other treatment. And the aim is to improve post-treatment outcomes, so it might be post-operative outcomes or post-chemotherapy outcomes. There's a really good broader definition in the BMJ, which is one of the papers you have. This is really a preparation for cancer treatment by optimising not only the functional capacity or the physical health, but also the mental health through needs-based prescribing of exercise, nutrition, psychological interventions. So you can see that whole definition is multimodal, which means there's multiple modalities involved, you know, physical activity, nutrition and psychological support, so at minimum three. And the aim of prehabilitation is really try and help support a sense of agency in people who are preparing for cancer treatment and to build their psychological and physical resilience. That's really, really important. Honestly, it makes a huge difference. So why prehab? Well, there is a good body of evidence in lung, esophageal and gastric cancer, colorectal cancer and breast cancer. And there's some studies in other types as well. And this is a really rapidly evolving field. So if you're interested in specific cancer and prehabilitation, go and have a look on PubMed. The general benefits depending on the cancer type is that it can improve perioperative functional capacity and quality of life and depending on the cancer type it might reduce either the length of hospital stay or post-surgery complications. It usually reduces healthcare costs, morbidity and readmissions and can also improve fatigue and psychological outcomes in terms of mood and may potentially improve survival. So in stage 3 colorectal cancer The prehabilitation was shown to improve five-year disease-free survival, which is what DFS stands for. There might be some specific benefits. So, for example, where we use things like pelvic floor muscle training or PFMT around a prostate cancer surgery, it can significantly increase the continence outcomes and the quality of life after surgery at about three months. So it is important to really look at it as an essential in the programme. So really, we know that prehab is common sense, but it does still need supporting evidence. And you will definitely find that the evidence varies depending on cancer type. So there was a 2022 review for lung cancer, which talked about the fact that if we are actually supporting physical activity and nutrition and stopping smoking. we're decreasing the side effects of cancer treatments in lung cancer and can improve patient outcomes and well-being. So it's a really good, strong statement from this review. And I would encourage you to read it if you're interested in lung cancer. There was also a 2021 systematic review. So that's what SR stands for and meta-analysis on the effect of rehabilitation on post-operative outcomes in people who've undergone abdominal cancer surgery. And really what they've shown is multimodal prehabilitation is unsurprisingly more effective and it might improve functional capacity before the operation and can reduce hospital length of stay. And what they defined as multimodal is really exercise include the whole body and respiratory exercises, as well as other things that may include nutritional psychology compared to standard of care. So we do see a significant benefit and what's really interesting is that prehabilitation programs have always been very heavily exercise focused and that's also probably because a lot of them have been driven and run for by anaesthetists who very much care about cardiorespiratory capacity of the patients to get through surgery. So physical activity is important but it is far from the only important thing and really that we need to include the others like nutrition support, psychological well-being is really the core three. That is absolutely essential. And what's interesting is to see the sometimes list. And this is from the Macmillan review. It's only sometimes that people get their anemia managed, smoking cessation and alcohol reduction and medication comorbidities review. And to me, it's utterly essential to do those things. So we know that unimodal rehabilitation has some benefit, but not anywhere near as much as multimodal. We should be trying to do the whole kit and caboodle as appropriate for the person. So there are a number of UK rehabilitation programmes. Again, this is from the Macmillan review that you will have. And I think they're going to be updating that if they haven't already. So you might have a local rehab programme. So do have a look around and see what you've got. What are the problems with prehabilitation, certainly within the NHS setting? Well, staffing and resourcing. We still have, we have a huge amount of cancer workload, and particularly with the global situation being what it is, staffing and resourcing is a significant issue. In the NHS, staffing crisis is really, really bad at the moment. So this is not going to be a big priority for them, even though it will reduce healthcare costs ultimately. They're inconsistent regimes usually, so... Nutritional recommendations can be really archaic and based on things like the eat well plate, which is not really the most evidence-based way to eat in cancer support, or they might just target malnutrition or obesity and leave the rest of the people behind. So really getting some consistency within that is going to be a significant challenge for research here. We do need more data on the right duration of intervention and what kind of combination is. particularly effective for specific patient groups and for me the key thing is that we can get a really good baseline for most people but we also need to have enough wiggle room to personalize that because as we know one person with colorectal cancer is not the same as the next so we need to be able to be flexible enough to adjust to the person's needs. So assessment you've seen this before is that nutrition physical assessment what can they do daily are they taking regular exercise and what is that. If they have access to a cancer exercise specialist or a physiotherapy referral in the NHS, do refer if possible or as soon as possible. You need to cover the basics of nutrition at minimum. Quite often you don't have a lot of time before surgery. So you do need to make sure that you at least have the basics in terms of protein, zinc, omega-3 fats, soluble vitamins. Do your bloods if you can before surgery. It is useful to get someone's baseline in terms of full blood count, liver and kidney function, metabolic profile, so fasting lipids, HbA1c, fasting glucose, inflammatory markers and things that are definitely relevant for immune function and anemia such as the iron profile, DB12 and folate. And these are usually easily obtainable in the NHS if you have a compassionate and cooperative oncology team or GP. And if you are suspecting deficiencies due to the fact that you're looking at the nutrition diary and it's very poor, then you might want to consider further testing to optimise that. And other assessment, depending on the case and the history you've taken and what your systems approach to cancer model will tell you later on. So baseline tests I've already outlined, but I did want to highlight the fact that you'd want to be optimising not only anemia, but also the NLR, so neutrophil to lymphocyte ratio. So ideally, we want to keep that, you know. low really, including the CRP as well. So both are inflammatory markers. So NLR is neutrophils divided by lymphocytes. And of course, we might be seeing other inflammatory markers such as CRP and ferritin. We want to make sure that before they go into the operation, they have the least amount of systemic inflammation possible, because that will help us overall. albumin is very important there's a very good evidence that prognostic nutritional index or PNI really has a significant bearing on someone going in for an intervention in terms of mortality and if you look at it literally look up PNI and any kind of cancer you like you will see tons of evidence on how it is a really important outcome influencer really so we do want to be able to optimize people's albumin and white cell counts as appropriate. So I've already mentioned it, but really we want to be able to do the multimodal. So nutritional optimization with a colorful anti-inflammatory whole food based diet. You can then adjust it to individual needs of the person as per your professional opinion. Of course, we need to be able to reduce harmful substances and smoking cessation is absolutely crucial because it really contributes to poor healing after surgery. increase the risk of clotting complications, alcohol reduction is also important, a wide variety of physical activity, so total body exercise, as well as trying to look at is there going to be a region in the body that's going to be particularly affected by that surgery and what should we do to prepare for any treatment-related problems. And this is things like, for example, pelvic floor rehabilitation, prehabilitation and rehabilitation around prostate cancer surgery. Stress reduction, psychosocial support, really important. And of course, medication, comorbidity review. So comorbidities are other medical conditions that the person might have. So things like diabetes or any other problems like with their thyroid. And that's important for the medics to do. Really, they need to do medication review of adequate control. of other problems and of course the appropriate management of anemia because we want to be able to have a really good hemoglobin count the best we can get before going into surgery because inevitably usually there's significant blood loss during that so nutritional optimization we always will start here and this is quite obvious but you know removing processed foods in general so there's been a lot of publicity around ultra processed foods so you should be able to point your clients to some good articles around that and to inspectors work around that you know processed meat we would want to remove completely and limit fresh red meat to the WCRF recommendations you know sugar sweetened drinks refined sugars damaged processed fats alcohol and also I would tend to usually talk to people about avoiding grapefruit because there's far too much interaction potential with various medications and cancers so for most people this isn't a I must have my grapefruit daily So we usually were able to substitute with something else. Moderate caffeine, as long as there's no issues with anxiety and they can tolerate caffeine. And of course, we want to be talking not just about what to remove, but really the priority needs to be about what do we eat? And that's what I would like you to focus your plans on is what to eat. So crowd out the bad with the good. So we want to talk about protein, fat and carbohydrate or PFC balanced meals. We want to have. the half a plate of rainbow vegetables seven ten portions daily one to two portions of lower sugar fruit ideally we want to have things that are high in antioxidants and low in sugar so things like berries for example or other temperate fruit um plenty of herbs and spices good anti-inflammatory fat balance so do talk to your clients about balancing their fats so extra virgin olive oil particularly organic and unfiltered is really king if you can get it avocado oil is good for cooking of course avocados themselves are fantastic to eat small wild oily fish we call the smash fish so that's sardines mackerel anchovies um herring and uh i'm trying to remember the other s i will post it later on um so yeah salmon and sardines there we go so salmon mackerel anchovies sardines and herring there we are So nuts and seeds as well, fresh and organic whenever possible, rather than having those roasted, salted, processed things with horrible oils added to them. We usually ask people to keep those in the fridge because they can go rancid reasonably easily. Using small amounts of organic butter, ghee or coconut oil, so saturated fats need to be present of course, because we do still need saturated fat, but not a huge amount. Of course, we do have a higher proportion of fat if people are going on a ketogenic diet at some point, although that's not usually something we would do before surgery. And we need to really make sure someone has a good omega-3 index. So dairy and soy, we'll discuss that really later. But as we've seen in general, in the evidence, you know, soy and dairy, as long as it's organic fermented and eaten in normal moderate dietary amounts, there's very little evidence that it would be a problem. But... The plain dairy, particularly milk, can drive IGF-1. So I would have a caution here. So I do tend to evaluate on a case-by-case basis. There are certain cancers that are particularly IGF-1 responsive, and we know in prostate dairy is not a good thing. So you do need to take into account the overall picture as well. So keep protein appropriate to the person's requirements. Normally we aim for around one gram per kilogram for most people. We would want to go up to 1.2 or sometimes even 1.4 gram per kilogram when recovering from different treatments, surgery, chemotherapy and radiotherapy, because there is a requirement for tissue healing that requires appropriate and adequate protein intake from a variety of sources. So do give people a whole range of sources they can pick from. Of course, organic whenever possible to reduce exposure to pesticides and endocrine disrupting chemicals and clean filtered water and then green herbal teas is appropriate. Now, it's still check interactions with herbal teas, although, of course, the amount is going to be a lot less than a supplement would give. If you are not used to drinking green tea and you want to recommend it to clients, it's important to tell them not to scald it. So you do not. put boiling water on green tea because that makes it really better it needs to be brewed around 80 degrees and to get the maximum egcg extraction and to help with the flavor so you can either leave it to cool for five minutes or so um after you put boiling water in the cup or you can get these kettles with different temperatures which is what i've got because i drink a lot of tea um so it is important to give people um options here because most people who say I hate green tea it's really bitter if it's brewed properly and maybe have a slice of lemon added and it's lovely because there are components in lemon that can stabilize the catechins from green tea as well so there's a bit of synergy going on there so when it's served like that most people actually enjoy it a lot more and of course these are general things if there is obesity or malnutrition specifically you need to target it as needed Why do I talk about the anti-inflammatory diet and why do I use it? Well, number one, it is in the middle. You can adjust it to whatever people want to eat, whatever protein source they want to eat. You can have an anti-inflammatory ketogenic diet if you're looking at different macro ratios. But the principle is really, really important. And what's interesting is that we know that the higher the dietary inflammatory index or the DII is, the higher the risk of cancer, the higher the mortality. Now, we know association is not. causation, but it is important to note it. So if you take the highest dietary inflammatory index category versus the lowest, people in the highest category have 25% increased risk of overall cancer, 75% higher odds of cancer, and a significantly increased risk of cancer mortality, 67%. So it's really, really important. Another study, they have slightly different numbers really, but again, it's really important to know. that the higher the inflammatory potential of the diet, really the higher risk for all cancer types and the higher the mortality that's caused by cancer. We also know that after the diagnosis of breast cancer and also ovarian cancer now, the post diagnosis DII was significantly associated with mortality risk. So certainly for specific cancer types, we know that what you eat after your diagnosis and how inflammatory that is may be associated with worse outcomes for you. And of course, we've been talking about the WCRF report in terms of different impacts of vegetable intake, fibre intake and cancer. So when we're talking about smoking and alcohol reduction as a part of our prehab programme, we talked a bit about optimising nutrition. If we're going to be reducing alcohol and supporting them in stopping smoking, there's some important resources here. I think it's important to actually highlight the risks here because most people are not aware of how alcohol increases risk of multiple cancer. And the Cancer Research UK website is fantastic for using the infographics and talking to people about it. People want to reduce their intake. Annie Grace books are great. You know, there's different apps like Try Dry, Drink Aware, One Year No Beer. GP and community services, if there's significant alcohol use, can be really important. For smoking, NHS provides a number of smoking cessation clinics. And there's GP support and Alan Carr's book people find quite helpful sometimes. So it's just a quick reminder about alcohol counselling. And I quite often will have these printed out in clinic or share that with people on our patient or client portal. So that people can really see the impact of drinking on their cancer risk. So this is kind of nutrition and harm reduction. So reducing the harm from alcohol and smoking, optimising people's nutrition. It's really important that all of us are aware of the physical activity guidelines for adults and older adults. And this is the government guideline here. We should all be counselling everybody who comes through the door around this. You might not be able to give them specific exercise recommendations because it's out of your scope, but you do need to advise them that that's what the government says around keeping active. So at least 150 minutes of moderate intensity. aerobic exercise per week or 75 minutes of vigorous intensity. We need to make sure they strength strain at least two days a week and a lot of people do not achieve that. That's absolutely essential to keep the bone mass and muscle mass. really nice and strong. We want to minimize overall sedentary time because going weekend warrior doesn't actually help us that much. So actually making sure they have frequent activity breaks to break up the sitting time at their desk is really important. And for those who are older, it's really important that the aerobic cardio strength training is also counted by balance. And I also put flexibility in. So I quite often count some way. clients around the three legs of the stool and then we add the fourth when we get older so the three legs are cardio strength training and flexibility and then the fourth leg we add when we get older is balance so it's really important in two days a week so there are things like you know tai chi and qigong for example yoga of course so it's important that we people understand that different kinds of physical activity and they need to use them of course if you're actually working with a person who has cancer They want to be able to access specific programmes. So for NHS, it'll be physiotherapy or local rehab programme. You have other private options, so things like cancer access specialist or can rehab. That's a training programme. They also have a website called Can Rehab Trust that can link to trainers in that particular geographical area. Can exercise as well. So do contact the training programmes and try and make local links so that you know how to cross-refer. There's also yoga teachers and yoga therapists who work with cancer and this will provide both physical activity but also psychosocial and emotional support and I have a list of people who work in this space which I will post for you. Unless someone is really fit previously and has no significant compromise after surgery I wouldn't use a normal personal trainer and it's amazing the amount of women who and I talk about women because I'm talking about breast cancer here but They've undergone breast cancer surgery, they might have had axillary node clearance, and they know they're at risk of lymphedema, yet they will go to a local gym and they will take advice from a PT who is not trained, who's getting them lifting heavier or for longer than they should, and then they get lymphedema. And that's much harder to manage once you've got it. Prevention is always, always better. So I would really caution people in taking advice from personal trainers, most personal trainers. in an average gym would be level two qualified and people who would we would want to be working with in cancer are level four cancer exercise specialists so significantly more qualifications and awareness stress reduction sleep is huge to try and support people with you can use number of different modalities that are listed here that i'm not going to go over but i think it's really important to provide different resources and links to charities and i've outlined a couple of things here There are different cancer specific charity resources, you know, say prostate cancer, ovarian cancer. So Target Ovarian provides a number of different free resources, of course, different breast charities. And you might want to also direct people to different resources for maybe, say, MBSR, for example, mindfulness based stress reduction or cancer recovery programme. And I've put in a link here. Different mindfulness apps have cancer programmes. You can look. them up and trial them you need to know what's on offer first before you recommend it and you might also consider EFT as a self-management tool that's emotional freedom techniques or tapping and that's got an emerging evidence base in cancer and Emma Roberts and Agha are the leaders in this area in the UK so psychosocial support I've mentioned it already you know you can use different charity groups, Wigwam groups are offered by Yes to Life with a coordinator. And I would really caution your clients in using internet groups very sparingly. People love to give other people advice that only applies to their personal situation. And it's really important that they don't take advice on supplementation and medications from people who are not qualified. And also sometimes the filtration in these groups. can be very tricky and some people find them really triggering. So kind of engage at your peril. I do find moderated groups provided by charities much more useful. So we talked about prehab. I'll just briefly run over some surgery types in common cancers. And of course, if you encounter some of the specific surgery, just look it up and read about it so you can understand the impact and the potential complications. So types of surgery for breast cancer. You can look at My Breast My Health. There's a fantastic website by Dr. Tasha, who is a breast cancer surgeon. So you can look that up. But effectively, we can remove the lump itself, the breast cancer lump, and it's called lumpectomy. Or you will see it called WLE, wide local excision. And that usually needs to be followed by radiotherapy in breast cancer. Or a mastectomy where the whole breast is removed. And you may be... offered to go flat if you want to, or you may have immediate or delayed reconstructions, and there are different types that you can look up. And there can be reconstruction from your own body tissue or a reconstruction with an implant. And usually at the time when someone does the breast cancer surgery, they will take a sentinel lymph node biopsy. And that can determine the need for ANC axillary node clearance. That means removing the nodes in the armpit that may have been affected by cancer. And the more extensive, the more nodes you remove in this ANC, the higher the risk of lymphedema. So these days we try and be as sparing as possible with removing nodes because we know it affects people's long-term well-being. And it's really important to advise your clients that early and consistent mobilisation, doing their physio exercises after surgery is absolutely essential to regaining their range of movement. which is what ROM stands for and reducing complications. And coding is another impact that can happen for people. So it's something to be aware of. And usually they'd be referred for some physiotherapy or tissue work after that. For prostate cancer, there's a radical prostatectomy, which is, of course, removing the prostate. And the extent of the surgery itself can be significant depending on what kind of clearance they need in terms of spread of cancer locally. Previously it was done as an open surgery, now it's usually laparoscopic, so keyhole surgery and assisted by a robot in many centres. Can be done as nerve sparing if it's appropriate and that's important for sexual function and it's really important to realise the most immediate problems for men and you know this is really significant for younger men who go through it as incontinence or leakage. And so pelvic floor exercise before and after surgery is really important. And when someone has had their prostate removed, other physical activity can be quite restricted in the first couple of months. You know, beyond walking, there's usually not as much you can do apart from pelvic floor exercises as appropriate. For colorectal cancer, there's different types of surgery. So colectomy is removal of the colon and there are different kinds of colectomies. So as you know, we have the ascending colon, then the transverse colon that run across the body, and then the descending colon. And depending on where the cancer is, we would then cut out the cancer itself and the region of bowel around it and the mesentery that's associated with it. So you can have left colectomies, right colectomies, transverse resection, sigmoid colectomies, or an anterior resection, which is quite a complicated operation really. If someone's bowel cannot be joined together safely or they present as an emergency or we need to give the bowel that's following the resection some rest, the bowel is brought out to the surface of the skin in a stoma. And I would really recommend that you go off and have a look at some stoma information because you will encounter people with it if you work with cancer, particularly any abdominal cancers. So the... Cancers can be a colostomy, that means colons brought out, and it could be on the right or the left actually, or in the middle. Or it can be an ileostomy. There are other ostomies as well, but ileostomies being the most common. And that's where the small bowel is brought out. And because the contents tend to be quite irritating to the skin, that one has a spout, so it sticks up a little bit more above the skin. So, stoma care and nursing input is absolutely crucial for people. So, usually they will get some counselling before it, unless they're presented as an emergency, in which case the person can wake up and they already have a stoma and they have no clue what happened really. So, it's also really important to know that it's a huge adjustment for someone who might be previously really well, who just got diagnosed, now have to cope with cleaning a stoma and the psychological and sexual impact of having one. Ileostomies can be quite problematic with high output initially so they can become really liquidy, you can have really significant fluid and sodium losses so it's really important to maintain hydration electrolyte balance and now we'll quite often really keep an eye on people's electrolytes probably on a weekly basis in the first few weeks of a stoma like that once they've been discharged. They're quite often given loperamide or imodium really to slow the bowel down a little bit but that can create its own problems. It's really important to know that someone who has an ileostomy has very different nutritional needs. They cannot eat a high-fibre, whole-food-based diet. They will need to be on a low-residue diet, but we can, short-term at least, in the first four to six weeks, they need to be on a low-residue diet, excellent chewing and avoiding anything that can trigger an ileostomy. But later on, after six to eight weeks, if the ileostomy is well settled, we can start reintroducing normal foods gradually. We do know that low residue diets, so that's low fibre diets that are needed for ileostomies initially can be quite problematic in terms of nutritional content, but we can get quite creative with juicings, small amounts of herbs and spices, etc. So do go off and actually have a look at different restrictions with ileostomies. So normally we can get, as I said, creative with things like skinless veg mash, for example, and, you know, small amounts of herbs and spices, juicing things so that people are not struggling with their nutrient intake. And again, keeping your protein up is going to be really important. So lung cancer, there's different types of resection depending on how much. you need to remove. You might do a wedge resection for a really small section of lung that contains the tumour. You might need to remove a whole segment or a whole lobe of the lung or effectively remove the entire lung, which is a pneumonectomy. And of course, depending on the extent of that resection, someone's respiratory capacity, their breathing capacity can be significantly affected. You can imagine just how much prehabilitation, rehabilitation is going to be really important for these people. So in terms of complications of surgery, these are general immediate complications are literally on table within 24 hours. Then there are early complications that you can read about here. You will quite often find that people will get put on clot prophylaxis, particularly people who are not going to be particularly mobile after their surgery. So definitely on clot prophylaxis in hospital. They can also go home with clot prophylaxis too. And that's really important because a PE a clot in the lung that's come from a clot in the leg can be fatal in these patients. And cancer is a pro-coagulant state, so cancer is a pro-clotting state, so it's really important for people to be aware of that. And of course different infections and sores are also important to think about. And leg complications very much depend on the surgery. It could be you could have bowel obstruction due to different adhesions, hernias around the where the incision was made, where the cut was made on the person. You could have a sinus, which is basically a channel that communicates to a surface. You can get a recurrence, of course, keloid formation, which is a kind of a thick, bumpy scar. And also the cosmetic appearance can be different, of course, depending on different surgery types and maybe other complications. Things like, you know, sexual urinary dysfunction with prostate surgeries, lymphedema with breast surgery, etc. So perioperative support, this is very much what you've already seen. So it's very much what you've seen in the troubleshooting video. So I'm not going to go over it in great detail. But this is really my clinical experience. Some of this is supported by evidence and some of it is really what I found useful in clinics. So it's really important to know this is effectively. my clinical opinion, where it's supported by evidence, I will give you the references and the list for that. So in my opinion, full prehabilitation program is really, really important before surgery. And you've seen the evidence of how it can affect outcomes. I tend to optimize people's zinc status to support post-operative healing. And it's really 15 to 30 milligrams daily. MCP or modified citrus pectin such as pectosol. can be given at five grams two to three times daily between meals, two weeks before, two weeks after surgery. Rationale for that really is to try and see if we can reduce the sieging around surgery because it's a galactin-3 inhibitor. However, this is not based on any significant evidence, just based on clinical experience and mechanism of action as a rationale. What we do know about MCP is it tends to have some stabilisation activity on PSA in prostate cancer patients. So that's the main thing. It's not been significantly studied in the perioperative period, but I'd love to see a good trial on that. It's mainly animal data in other indications. Do make sure that you tell your clients to omit all supplements that may affect bleeding and clotting at least a week before surgery. So you can check the natural medicines database, but the common list is here, for example. Some people who go for their pre-op check, they will run over the list of medications. with their nurse two weeks before and so you just stop it at least one week but perhaps even two weeks depending on how high risk the surgery is before that. Ensuring good stress management and mental preparation going into surgery with a positive attitude is really, really important and also being prepared. So hospital bag lists can be really useful for people who are feeling really overwhelmed and their breast list is here on Future Dreams website. So Sarah Lyon Age and the Future Dreams. House have collaborated on creating a big resource list for people with breast cancer. So you can look at some prep planning guides for chemotherapy, radiotherapy or surgery, for example. What's important to realise is that resection in and of itself, so going into surgery, induces unsurprisingly physiological stress response, but also an immune dysfunction that may potentially facilitate metastases. And there's been some interesting papers around that. This is why what's been explored is sometimes giving people perioperative beta blockers or some very specific anti-inflammatories such as NSAIDs or COX inhibitors, particularly around gastrointestinal cancers. But really, it's up to the medics to do that, and you wouldn't be participating in that. But this is just something to be aware of. We want to try and that's why we want to try and minimise inflammation before someone even goes into surgery. We want to try and minimise the opportunities for creating an unfavourable environment. So after surgery, they don't really need a usual detox supplement in terms of they don't need to go on any weird and wonderful fasts. They need to be supported in recovery. So easy, nutritious, whole food based regime, lots of good colors, sufficient protein, you know, up to 1.2 grams per kilogram, sometimes high up to 1.4 if it's needed, if someone's really compromised and, you know, has lost a lot of muscle mass and need to build up. Good protein, fat, carbohydrate balance, you know, consider continuing with the zinc after the operation. You might also consider systemic proteolytic enzymes, things like, for example, seropeptase on an empty stomach to help with tissue healing. Again, as I said, pectosol, I tend to use for two weeks before, two weeks after for any cancers that might have a significant collecting three contribution. Vitamin C and vitamin A rich foods, of course, A not an excess really and it's really important to realize when people coming out of surgery they normally come back home with a whole ton of medications afterwards so they might have something for their pain like an opiate but then they will need a laxative to go with that because opiates constipate people can make them nauseous so give people a pre-emptive plan most of them will be given some pain relief and most of them will be given opiates such as you know morphine or dihydrocodine or codeine etc. So talk to them about having some magnesium citrate with plenty of water. You can also use things like colnarex or colosan as a powder. You can use truffalo or dandelion coffee again for gentle support if there's no interactions. It's really important to give them some idea of how they can help support themselves and if they're a bit nauseous with opiates instead of taking anti-nausea medications they can also constipate someone such as lecandansetron. You might want to try things like seasickness bands or going for acupuncture, for example. So early physical rehabilitation, I hope I've convinced you now, is also really important because we're prehab, but we also need to rehab. And this is really, really important. And it started as early as possible. And you can actually see now all of these enhanced recovery after surgery or ERAS programs, where they just get people up as quickly as possible to try and reduce the risk of complications and clot. Now, once the wound has closed and healed, you might consider using a little bit of sweating via exercise or infrared saunas just to try and support very gentle, normal detoxification, physiological levels, not major detox regimes. Once the wound is healed over, you can also use things like topical vitamin E oils. So Fushi has one or rose hip oil with a few drops of. some supporting essential oils if people are not sensitive to those or I really also like the gotu kola infused oil from ashadi which is really nice and supportive The only thing to mention with gotu kola is that you don't want to expose your skin to sunlight immediately afterwards. But to be honest, all of your clients or patients should be counselled to put some protection over their scars. It is really, really important. So scar work can be highly beneficial as soon as the wound has healed. We've had really great outcomes with it. So you can look up some scar work information here. And Emma Holly is one of the key trainers in the UK. And we're fortunate to have Octavia at the clinic as well, for example. But you can look up at who might be doing this locally with you. Other considerations, again, where someone is already compromised in terms of liver function, where maybe they've had chronic alcohol use or they might have had non-alcoholic fatty liver, etc. I will give Silimarin for liver protection in the run up to surgery. and then after surgery and then we usually aim to reduce the inflammatory aftermath of the surgery and that's the stuff that can you know can potentially facilitate spread that's what the literature is suggesting we don't know very much about it we need to do further research but I would usually give things like you know bioavailable curcumin plus or minus boswellia and you know gingo for platelet activating factor or willow bark as needed do remember that willow bark you have to be very careful with anybody with the salicylate sensitivity you don't give it and you don't give it to anybody who's allergic to aspirin. You might want to also reduce this kind of pro-thrombotic, pro-coagulant effect so more clotting after surgery with things like ginger, curcumin and garlic again always using in food in general but can also supplement as appropriate. Support immunity with mycotherapy throughout you can use astragalus after surgery as well. And of course assisting with side effects, I mentioned nausea is a common one when either people have had a GI surgery, so abdominal surgery, nausea is quite common, but also when people are on opiates such as morphine and codeine because they're just feeling a little bit icky really. So things like ginger decoctions or those seasickness bands on P6, the pericardium 6 acupressure points can be really handy. Thank you very much for listening. I hope you found it helpful and I'll see you in the next lecture. or endocrine therapy. ________________ 2.5 Radiotherapy and Hormone Therapy Insights Hello and welcome back to the Systems Approach to Cancer programme and today we'll be talking about radiotherapy and hormone or endocrine therapy support. So let's talk about radiotherapy. Radiotherapy is really using ionising radiation to deliver lethal or sublethal DNA damage to the cells and different tumours in different normal tissues have different radio sensitivity which is why we can use radiotherapy for some tumours but others might not respond very well. And having this knowledge at our fingertips actually helps us plan radiotherapy really effectively for people so that we know not to deliver excessive damage to some crucial normal tissues in the area. There are three main types of radiotherapy, so teletherapy or external beam radiation therapy is the most common. That's a typical one where you the radiation source is external to your body and is delivered to your body. And usually you would have a planning scan for radiotherapy and then would have your radiotherapy delivered in fractionated small doses every day, Monday to Friday over a period of several weeks. But again, you can use sometimes quite compressed regimes. So it very much depends on where you're at. There's brachytherapy, which is local implantation of a radiation source mainly used in things like prostate cancer and cervical cancer as an example. Intravenous injection of radioactive isotope is mainly used in quite very small specific cases. The key thing to say as well, there's of course very specific techniques that we now use anything like gamma knife for example, stereotactic radiotherapy. So there's a number of different ways in which we can really progress and there's also been a creation of proton beam therapy centres in the UK. So this field is rapidly evolving and will continue to do so. In terms of general nutritional considerations for radiotherapy, of course, we're going to do the usual baseline of an anti-inflammatory, high-fighting nutrient, diverse whole food based diet and support regular physical activity to reduce fatigue. And that's really, really important because people sometimes can get through chemotherapy not feeling too badly and can be really flawed by radiotherapy at some point. I've put in a review on natural compounds and how they might protect normal tissue against radiation-induced injury. And you will see that actually having this baseline diet that's anti-inflammatory and really focuses on incorporating different colours and high phytonutrient content can be really important for delivering all of those bioactive compounds. It is really important that people have excellent blood sugar and inflammation control at minimum before starting radiotherapy, so you will need to assess for that and correct. IGF-1 signaling is involved in radiotherapy resistance, so it's also important to make sure that people are not having excessive stimulation of that axis. Pre-radiotherapy fasting may be of some benefit, although there isn't the same amount of research as there is around chemotherapy. And there is evidence for ketogenic diet to... be used for potentially increasing tumour response and maybe reducing treatment side effects. We certainly know that a number of trials have shown benefits for body composition, which we would understand really. And there was one study in breast cancer patients that showed significant improvements in function, both emotional and social, as well as sleep quality and side effects. Do I put everybody on ketogenic diet during radiotherapy? No, it needs to be evaluated on a case-by-case basis both in terms of feasibility but also overall contribution of someone's blood sugar metabolism to their situation. However, I will use ketogenic diet or at minimum a low carbohydrate diet with people who are pre-diabetic and certainly, you know, heading into diabetes. I'd want to try and reverse them out of that as quickly as possible before radiotherapy. So that's definitely one of the indications. There are various mechanisms for the ketogenic diet being used in radiotherapy, and I know you can't really read that very well on here, but there is a whole review if you want to read on this. And ultimately, the idea is that ketogenic diet can really benefit from a number of different levels in terms of particularly looking at radio resistance. So that means that by decreasing glycolysis, and trying to force tumour cells to really switch up their metabolism, it may be that they basically become a little bit wobblier from that perspective and become more radius sensitive. That's only one example. There are different mechanisms from DNA damage to cell cycle redistribution, etc. But this is something to look into. How do you find out more about the ketogenic diet in cancer? We don't have a specific ketogenic diet module. But you might look at Keto for Cancer books and recipe books such as Ketotarian or Patricia Daly's book. She used to run an education course for professionals, but I'm not sure whether that's still running. But if you want to start someone in general ketogenic diet, you can use the IFM Mito plan with adaptations. So you can remove the starchy veg, grains and fruit servings and really make sure that people are having the net carbohydrates at 22 and 25 grams. And that means limited amounts of rainbow non-starchy veg, but trying to include plenty of culinary herbs and spices to keep things anti-inflammatory. Protein should be measured at around one gram per kilogram body of weight, and then usually fat for the rest of calorie content. And I tend to use extra virgin olive oil still as the main king fat really, with MCT to top up to ketosis and avocado oil for cooking. It's really essential that people use keto monitoring of some sort. So I use chronometer for nutritional intake and Keto-Mojo to monitor ketones in GKI, which is Glutose to Ketone Index. And we really are targeting one to three for therapeutic ketosis and three to six for nutritional ketosis. And there's tons of resources on the Keto-Mojo website. It is really important to know that I don't really support a high saturated fat ketogenic diet. I I always aim for more anti-inflammatory Mediterranean style fat content in the ketogenic diet that I use. People can get keto flu. So that's when they feel really quite horrendous getting into ketosis. And it's really important to warn people they can take three to five days to get into ketosis. And during that time, they might be feeling a bit tired and a little bit icky. You can use ketone esters. They're not very tasty, but they can be really useful for putting people into helping. to get people into ketosis, use good hydration with electrolytes and use longer fasts. So usually maintaining 14 to 16 hour overnight fasts to get help get into ketosis if people's weight is stable or weight loss is desirable in that particular person. Other general considerations you might want to refer for specific support. So melatonin is used for radiotherapy support. It has interesting effects on radio sensitization of tumor cells and radio protection of normal tissue. There may be some phytomelatonin that people can use, as I know you're not prescribers. But however, there doesn't really have any evidence that has the same benefits. So it's a little bit tricky. So whatever possible, particularly if people also need sleep support, you can either refer to GP who can prescribe. doses of about two milligrams or so, three milligrams on the NHS or use integrative functional medicine, doctor referral. Other modalities that can be used to synergize with radiotherapy could include HBOT, so it's hyperbaric oxygen therapy. And ideally, the person going for that treatment should be in ketosis and sometimes may need to top up with either high fat snack or some ketone esters before therapy. And that's important because we don't really want to go into a well-fed state. We want to apply as much pressure as possible. So that means if you want to be able to go in a sort of ketotic type state, even if you're not doing ketogenic diet, if you go after a really good long overnight fast and you're topped up with esters or a high-fat snack and go for age-bot in the morning, you would usually be in ketosis during that time. even if it's not going to be deep ketosis. Proper pressures should be used. Usually we use MS centres and of course it's not really up to you to decide. There would be usually a medical referral if they need one. And what we do know is that HBOT does improve local tumour control and recurrence for cancer of head and neck, definitely. And there is some less solid evidence in other tumour types. We do use it and we do find it very helpful. There's some evidence that local regional hypothermia can be useful, but there's poor access for this in the UK at the moment. So radiotherapy can have multiple toxicities and they're really due to direct tissue damage in the radiation field. Of course, if we can be really precise with our radiation delivery, then we get less collateral damage. And one of the most common side effects is radiation dermatitis, so that's skin irritation and there can be an increased infection risk associated with that. Any left sided chest radiation will have a potential side effect of cardiac damage. We use things like breath holds to try and reduce that as well as more precise radiotherapy planning and any chest radiotherapy would also target the lung to a certain degree so there can be some consequences for that. So you could remember wherever the radiotherapy is delivered the local tissues in the area could be affected and we've seen this slide before around different radiotherapy side effects depending on where the radiotherapy is given. So radiation dermatitis, usually acute, is within weeks of starting radiotherapy and can range from just slight mild redness, as you can see at the top, to D, very significant skin erythema, you know, moist or dry disquamation means peeling off the skin layers and or ulceration. What's really important to know is actually the peak effect of acute radiation dermatitis, or ARD, can actually be two weeks after someone stopped radiotherapy. So there is a tail to it, which is why we need to continue supporting people at least two weeks after radiotherapy to minimize the damage. And there's some chronic radiation dermatitis effects, so fibrosis, so contractions and damage to the tissue. In that way, skin atrophy and pigmentation, as well as little veins called telangiectasis, little blood vessels that can form in the area, and that can happen months to years after radiotherapy. So in terms of radiation dermatitis, usually they say no topical agents on the skin two hours before and four hours after treatment. Usually we need to make sure that no commercial creams are used that can contain metals. Conventionally, there's various things that can be used for radiation dermatitis, usually topical steroids. I'm not really a fan of those because they thin the skin. So integrative recommendations, there's a whole ton of various topical things that have come up. So aloe vera has not been recommended because it's not been particularly effective. There have been trials that show it may potentially have some benefit, but plenty of trials showing it has no benefit. Topical calendula is a bit the same. Oral curcumin is quite interesting. So people have said six grams daily may be effective in one small study, but in a larger one it wasn't. So jury's still out. I do have to say I find it effective in clinic. There are two trials in the Vico cream, which is turmeric and sandalwood in head and neck and breast. Cancer radiotherapy is showing some reduction in dermatitis, and I do find it's effective in clinic. However, it is bright orange because of turmeric, so it will stain clothes and bedsheets. So that's just something to warn people about. Various topical gels from EGCG sprays to silimarin 1% gel to black cumin seed 5% gel. have been shown to decrease the severity of radiodermatitis. The problem is the commercial availability of these treatments. EGCG is notoriously unstable. And so in most of these studies, researchers have actually prepared the spray in the laboratory daily almost. So you've got to remember that if we recommend it to someone, we can't just pull out a study. We need to be able to source a product, which is why at the moment, most of the time we do suggest VicoCream. um rather than the others because the others are not easily commercially available but if you find one let me know mucositis so that's radiotherapy delivered usually to the head and neck area in particular so honey or administration of honey could potentially be useful and can be given as ice cubes so we tend to use manuka um zinc um you know zinc sulfate has been studied although it might not be as effective i do find zinc carnosine very effective but you've got to check i'm pretty sure band does not allow the use of that we do use it in clinic um as i can prescribe but licorice is interesting it may be of benefit there's different preparations have been studied ayurvedic preparations um as well as different films And you might want to get a solid preparation like a licorice and thyme extract, for example, from botanicals for life and get people to rinse out their mouths with that maybe twice daily. Just a pipette full rinsed around the mouth for about 20, 30 seconds and spat out. Topical vitamin E, there's a question mark on that and glutamine may potentially be effective. But because of the concerns around glutamine being used as a part of the cancer metabolic pathways. I tend to use other agents instead or using the lower end of the range, so no more than 9 grams really. Diarrhoea is relatively common with radiotherapy being given to the abdomen and pelvis. Glutamine has been studied at really high doses, so you can imagine 15 grams TDS, that's three times a day, is 45 grams. If you consider your overall protein requirement as being... you know, say one gram per kilogram in a 70-year-old, 70-kilogram-weighted patient, it would be 70 grams. It's a huge amount of glutamine as a percentage. But actually, I don't tend to find it very effective. I know it is loved in Australia, but I don't tend to use it very much in clinic. Probiotics, however, we do use. And there's several meta-analysis showing benefits. for probiotics with a significantly lower risk of radiation-induced diarrhea and reduced medication use as well. And these are some examples. This is a recent probiotic review, and I think that's a 2022 one, showing some of the examples of different formulations that have been used. And you can see they're largely mixed formulations, apart from lactobacillus rhamnosus in the first study. I have to say I tend to use Saccharomyces boulardii with great effect during radiotherapy because it also supports mucosal immunity etc. even though there isn't necessarily a big evidence base for it here. So it's my clinical experience. Other parts of clinical experience this is not supported by any significant clinical evidence this is just what I find useful. I tend to want to reduce the potential negative impact and side effects by using adaptogens. and also things that could radio protect the normal tissue and radiosensitize the tumour tissue. Serves of adaptogens, I tend to use things like Siberian ginseng, so Eleuthera coccosin ticosis and astragalus, usually before, during and after radiotherapy to support the immune system and provide some adaptogen support. I use berberine with moderate dose curcumin during radiotherapy to reduce the risk of... you know, radiation-induced damage and use higher dose afterwards. And really with those approaches, I have to say we have no grade three, grade four radiation-induced dermatitis in clinic for years now. We also aim to reduce the pro-inflammatory effects of radiotherapy with Gingko and Boswellia after radiotherapy. I don't always use both. I quite often use Boswellia in combination with curcumin, and that tends to be enough. We support immunity with mushroom therapy and astragalus, as I mentioned throughout. So that's what we tend to do for radiotherapy in clinic. So let's now move on from radiotherapy to hormone or endocrine therapy in different cancers. And usually the most common cancers where people are using them in breast cancer, prostate cancer and endometrial cancer. So breast cancer. we can use tamoxifen, aromatase inhibitors or ovarian suppressors. And we tend to use tamoxifen as a selective estrogen receptor modulator, usually in premenopausal women. Aromatase inhibitors tend to be used in postmenopausal women. Where they're used in premenopausal women, they're usually given with things like Zolidex to really suppress ovarian function. Prostate cancer, you can use, again, gonadal suppression like gossirelin or Zolidex. You can use androgen receptor antagonists, there are others as well. This field is moving relatively rapidly, so you will find more different medications in the guidelines, and you can look at different treatments available on the ESMO and the Macmillan website as well. In endometrial cancer tends to involve progestin therapies in general. So for breast cancer, you will see the common side effects here. They tend to be really menopausal side effects. And for ovarian function suppression, it's really abrupt menopausal symptoms in particular. So for managing menopausal symptoms, I have given you a separate lecture that I've done for BANT on cancer menopause support. But this is just a quick one slide summary of things to consider for VMS, aves and motor symptoms. And these are the things like hot flushes and night sweats, for example. AIA is aromatase inhibitor induced arthralgias, joint pains and aches that you can get with aromatase inhibitors such as letrozole and nastrozole. AIBL is aromatase inhibitor induced bone loss. So that's osteoporosis you can get with those medications. Of course, sleep disturbance is really common and vaginal symptoms and sexual dysfunction. So. You can have a look at the general summary here. And of course, the full information is available in my other presentation. So for ADT, which is androgen deprivation therapy, that's what's used in prostate cancer to effectively try and deprive it of the testosterone and dihydrogystosterone as a potential source of growth in this cancer. So androgen deprivation therapy has. effectively very much andropause type side effects from hot flushes to osteoporosis, fatigue, depression, erectile dysfunction, metabolic syndrome. So this is really important to keep in mind. And progesterone based therapies that can be used in endometrial cancer, though they're very much more rarely used now, can really promote water retention, weight gain, breast discomfort, fatigue, nausea and loss of libido. So I'm going to just introduce you to a couple of very general integrative management of side effects, recommendations, some for breast cancer, and then a very brief outline for prostate cancer. I mean, we could talk about this for days, really, but this is just a brief outline to get you started. So this was, you know, really ASCO SAO guidelines 2017-2018. And you can see the full guideline available on the SAO website. Now of course they do need to be updated so they're quite old now but it's well worth keeping them in mind in general. So grade A and grade B is what we would call high evidence grades and that's the things that we need to pay most attention to and grade C and grade D, grade C is kind of wobbly really wobbly evidence and grade D is kind of poor evidence really. So if you look at anxiety and stress reduction, for example, you're looking at meditation for reducing anxiety at grade A. And grade B, you're looking at general stress management, sort of group programs, music therapy and yoga, for example, for chemotherapy-induced nausea and vomiting, acupressure and electroacupuncture at grade B evidence in particular. For depression mood disturbances, mindfulness-based stress reduction, so MBSR programs and meditation, relaxation and then at grade B you're looking at yoga, massage and music therapy. For fatigue most things are grade C evidence but here we might be looking at things like hypnosis, acupuncture, yoga and ginseng potentially. Lymphedema not much here. very little on neuropathy but that was a really old guideline. For pain we now have an updated guideline so we should be looking at that and for quality of life meditation yoga grade A and grade B and grade C are things like acupuncture, injectable mistletoe, Qigong reflexology and stress management in particular and really important to know that this is subcutaneous delivery only this is not oral mistletoe so it's really important to know that Usually the orally available stuff, number one is homeopathic, it's not actual mistletoe. And all of the studies that are truly evaluated, they affect... on cancer outcomes have all been injectables. And then gentle yoga for sleep disturbance. So this is just a very brief gander through the breast cancer guideline for integrative oncology. You might want to have a read through it, but do remember this is quite old now. So we really have evolved the evidence quite significantly in the last five years. So managing prostate cancer prostate cancer hormone therapy side effects, exercise is absolutely essential. And that's really important and has been acknowledged in a number of papers from conventional oncology. And there's a 2020 paper that says prescription of exercise medicine should be a routine part of prostate cancer care. We want to combine several different modalities, so moderate to high intensity aerobic exercise, as well as resistance and impact exercise to really manage that cardiometabolic and bone loss side effects. And again, as outlined before, we really want to see an experienced physiotherapist or cancer access specialist here. For hot flushes and a typical kind of andropause type side effects, acupuncture shows some preliminary evidence of efficacy without side effects. It's not strong evidence base, but we do recommend and we do find effective in clinic. Sexual health, they would need specialized advice from a psychosexual therapist or sexual advisory service and there are some of those around the country and privately Percy Health has some of those available as well. And in terms of general advice I think it's really important to know that putting someone abruptly into andropause with the ADT, androgen deprivation therapy, has a significant metabolic impact on someone. So the metabolic profile assessment management is essential. So at minimum Apart from the general bloods, you need to get the Hb1c fasting glucose and fasting lipids and manage those properly. People who have never had any problems with those suddenly start having problems when they start on those drugs. And of course, in general, you are aiming for kind of largely plant based antioxidant rich diet. Again, anti-inflammatory emphasis on cruciferous veg, tomatoes, particularly cooked tomatoes with nice natural fats such as extra virgin olive oil. natural soy, pomegranate, marine omega-3 fatty acids, reducing saturated fats and avoiding dairy. And there may be room for vitamin D and potentially plus or minus omega-3 supplementation. People cannot get it through the diet properly alone. So thank you very much for listening. I hope you found it helpful and I'll see you in the next lecture. ________________ 2.6 Managing Interactions in Integrative Cancer Care the cancer program for nutrition professionals And today we'll be talking about managing interactions in integrative cancer care And here we'll be talking about really mainly about you evaluating uh how supplements may interact with medications and there are different types of interactions So we're going to start by looking at pharmacocinetic interactions and that's where the nutrient or the herb or whatever supplement you want to use might change the absorption metabolism or excretion of the drug and that means that the drug's activity itself may be increased or decreased And the example of this the most common example you would have uh looked at in your training would be phase one or phase 2 hippatic metabolism interactions So cytochrome P450 enzymes are part of our phase one system and they are quite often affected by multiple things anything from environmental exposures to medications and to nutrients and herbs So that's the pharmaccoinetic side but you can also have pharmacodnamic interactions and then that means that the actual effect of the drug uh by binding on to a receptor or different post receptor effects or chemical interactions might actually affect the action of the drug and may also affect the side effects and the example of a phicodnamic interaction can be two things with a similar effect adding together So for example seditives things that you know calm you down and also uh make you sleepier all adding together So for example say melatonin on top of a drug that also makes you a bit sleepy Things like can lead to increased sedation So that's an example And they can generally be divided all these different types of interactions into synergistic additive or antagonistic And synergistic means that 1 plus 1 doesn't equal two like in additive interactions but 1 plus 1 might equal 3 4 5 or six So a better effect that you would get from just adding things together And these can be intentional as nonintentional as we know and many people are really quite unaware of how many things are interacting with what they're doing You know one example being grapefruit juice for example People are still not aware of the fact that it can interact with multiple medications So my proposed guidance on assessing interactions in the cancer support setting is to always load all medications into the interaction checker So that means not just chemotherapy or their targeted medication but also different painkillers maybe anti-nausea medications maybe anything else you're taking like over theounter medications like paracetamol um if they're in a PPI that needs to be loaded in You need to check each supplement carefully uh against the list of medical cautions and contraindications and you will have those in natural medicine's database So you need to very carefully check each supplement against a whole list of medical cautions and contraindications Um and you derive that list from the list of diagnosis for your client or your patient So for example some might have cancer and diabetes or cancer and autoimmune thyroiditis or cancer and rheumatoid arthritis So you need to take all of this into account And I do mention that cancer and autoimmune disease combination can be tricky mainly because there are some drugs that we use for autoimmune diseases to suppress the immune system that can also lead to increased risk of cancer for example and it can become quite a tricky medical decision uh when someone does get a cancer diagnosis or how to manage the combination of that So document what you find and what your plan of action is with reasoning behind it just in case there's ever any complaint or there's any uh query from pharmacy or oncology you can go back to your records and really see why you've decided to do what you wanted to do So major interactions my advice is avoid um minor interactions that might come out um on the natural medicine's database You can really dismiss them if you think benefit outweighs the risk and if you think the whole person might benefit from this intervention So you can say okay well I've considered it but actually benefit outweighs risk and that's why I decide to go for it And moderate interactions really do require a bit of a detailed dig And that means that you need to see what the pros and cons are and potentially also discuss them with your client to see if that intervention would be beneficial in a different context And apart from the impact of the interactions which is you know minor moderate and major we also have a grading of evidence on things like the natural medicines database and grade A and grade B You must pay attention and usually this means that there is a human study that shows something affects uh drug metabolism um and you do need to know the mechanism um of it So the mechanism of how that might interact and you might actually evaluate and to see if it's of relevance So for example if you have a grade B evidence that something interacts with oral absorption of a drug but you know that drug is given intravenously you can say okay well this is not relevant to me so I can disregard it And uh if we're looking at grade C or D of evidence this is usually in vitro data that's of really limited relevance to us So we can really disregard it if it's minor moderate interaction and if you think the risk benefit is favorable So some general rules of thumb and I know some of these are really basic but it's worth reiterating So if a supplement inhibits the enzyme that's used to break the drug down the concentration may increase above the levels we would normally expect and this may cause more side effects and in certain drug classes they can have a significant impact So chemotherapy having one um increased side effects will be quite significant but also things like anti-coagulant drugs So uh drugs that cause an increased risk of bleeding if you further increase that um that can have some significant consequences for the person uh and if a supplement induces the enzyme that's used to break the drug down So if it actually upregulates it that means of course we're breaking more drug down So the concentration of the active medication may decrease below the levels we would expect and that can reduce the effectiveness And of course for anything that's used to control cancer treat cancer in terms of medications then that would be significant because you might have potential impact for disease control So this is something you really really do need to watch significantly And information on the different um enzymes that are used to break different drugs down can be found in medicines or UK as well as natural med medicine's database has some of that um information too So there are some special cases however where actually the enzymes we are talking about do not break the drug down but actually activate the drug and temoxifen is one of the most common medications used in breast cancer that actually requires activation So tmoxifen is not particularly active It requires conversion via two-step process to indoxifen which is the active metabolite And it's the indoxifin levels that really count So here you can see uh in the diagram there's two steps and they can go in either direction really in terms of you can have cip 3 a4 or a5 involved in the first step and then cip 2d6 or vice versa It can be cip 2d6 first So we know there's two enzymes that we do not want to be messing around with particularly But what's interesting about it is here inducing an enzyme like CIP 3A4 or inducing CIP 2D6 would actually increase the effectiveness of the drug rather than decrease it And that's because those um SIP enzymes are not used to break the drug down They're used to activate the medication So that's a different direction of effect So that's important to realize that there are some drugs that behave in a different way So looking at some other general rules of thumb as examples um things that uh will interact with warerin for example you would need to really be very very careful with and there's things like cip 2c9 substrates so I suggest avoiding those as an NT and obviously you will avoid vitamin K supplementation with warin um and generally with any bleeding drugs um so any anti-coagulant drugs you do have to be extremely careful because interf interfering with the bleeding or clotting can have severe consequences for the person Uh there are some other examples you know no turmeric or curcumin supplementation with tmoxifen being one example where it was found in a human study that the exposure to endoxifen which is the active metabolite was significantly decreased when highdosese kurcumin was supplemented So we don't use that doesn't mean we can't use turmeric in food at normal levels We don't stop the whole population of India for example um in terms of eating turmeric if they are on tmoxifen but we would not want to use highdose oral supplementation Other examples maybe echynatia can be a bit of a problem with some of the things that are metabolized via cip 3a enzymes uh and also St John's wart as we know interacts with multiple different um enzymes such as CIP 3A family cip 2C9 and P glycoprotein and usually we strictly avoid that and personally I always avoid St John's warts completely during chemotherapy because also on multiple other medications as well And I usually also give the same advice about grapefruit because so many drugs are detoxified um and eliminated via cip 3a4 and usually the pharmacist would give them that advice anyway but this is just as a backup and you can read a little bit more about on the FDA website So when we are actually assessing clinical interactions how do we know whether something has clinical significance so just because something is been poured on some cells and may show an inhibitory effect or an activating effect does it actually really matter so the what we ideally want to see is evidence that's in point one evidence that's confirmed for clinical observation in studies and that's for example interaction between St Jones wart and dejoxin there may be things that are attributed from clinical reports which are probable or possible So that will be a lower level evidence but still something to consider Number three is really where a lot of the evidence lies because most of the supplements have not gone through proper pharmaccoinetic testing uh in combination with supplements So most of the time it's speculated from what we know about the pharmarmacology of the herb and the drug and that can be different It can be probable possible speculative or highly speculative So really if it's probable you probably need to pay attention to it If it's possible you need to really evaluate risk benefit and see speculative and highly speculative um you probably need to again take with a pinch of salt and decide whether the risk benefit is worth it And of course there's also can be inaccurate or misleading uh information out there which is based on mistaken assumptions about you know herbs or supplements or the plant parts used or pharmacological effects and there's plenty of them as well So you do need to keep an eye on it I would say when you're just starting out in this area just pay attention to the rating So you know minor moderate major and the grading of the evidence And then once you become more confident you can evaluate things a little bit more from primary studies So these are some examples of assessment So for example we've got a very typical combination of um chemotherapy with epubicin cyclphosomide That's the EC phase of ECT commonly used in breast cancer And people also can get given dexamethasone which is a steroid during this particular uh therapy and certainly with taxes as well the following phase Now I would maybe want to give this person a strugglers So if we're actually looking at cycllophosphomide um and a strugglers you can say interaction rating is moderate but level evidence is D and actually it's about the fact that a stragglers might counteract imunosuppression by dexamethasone Well dexamethasone in this case is actually used quite often as an anti-imetic anti-nausea medication rather than to further suppress the immune system Um and in the taxing phase it's used to reduce uh the potential for reactions to the taxin medication So here we're really not necessarily that concerned about is level evidence D it's a moderate interaction If I want to use a stragalus to try and support someone's overall well-being and to support um their immune system I will go still go ahead and use a stragalus in this setting Um so you can see that and but this might be a very different um risk benefit if we're actually using at someone who some someone who's on highdose steroids for their polymyalgia rheumatica and we'd want to give them a stragalus where their steroids are used to control their autoimmune disease So maybe a struggle This is maybe not the most appropriate herb to use here and you'd want to do something has a bit more of an immunom modulating effect that's friendly to use with steroids So keeping up to date we really want to make sure that when you do check interaction uh you ideally use at minimum the natural medicine's database but also quite often for particularly newer drugs and also something you have only encountered for the first time you'd want to also use PDME to check for updates because you've got to remember that any uh books on drug interactions or any even database on drug interactions out of date to a certain extent because it takes time to read the research get it into the database and get it available to the public So really we're looking at a minimum of one to two years of being out of date from the database world most of the time Um and you please do use this drug for new uh use this rule for new drugs in particular Anything you don't know or anything where the risks are particularly high if you get something wrong you really need to make sure that using both sources And remember if in doubt leave it out You know you never very well I don't think I've ever regretted not giving a supplement but we do know that people can um really kick themselves if they've given something that can interact with the medication And not to forget as well just to mention that if you do give something that has a significant inter interaction with medication you haven't done your due diligence that will of course undermine you um as a practitioner in front of the pharmacist and the oncologist who's treating the patient So we want to make sure we're doing our very very best for the person who we're looking after uh as well as making sure that we uphold the professional standing of nutritional therapy in the world So um please do your due diligence do ask for help on the group during the course if you really want some Um so you can post a snapshot of the wording for the interaction but I do really see the whole text because I won't be able to go into the program myself to check it individually And if you're ever asking for help on interactions you do need to always post the clinical context because the interaction between a drug and um a supplement is never without a background We need to know age or gender at birth or the medical diagnosis any other medications and anything that might be struggling and why you actually thinking of using that supplement Is there an indication for it more is not better Targeted is definitely better So we need to know why you're thinking of using that and what you're concerned about There are other programs and mentorships available I know Deborah Grayson has um a great mentorship uh for pharmarmacology Being a pharmacist she's fabulous So that's another example of where you might want to dive deeper But do remember that you're always responsible for your plan It is a privilege to look after people who are unwell but it's also responsibility And no mentor teacher can take that because it is up to you to decide how you want to proceed Um and it's not to scare you but just to make sure that you do um take this with an appropriate level of gravitas and you do all the background checks that are important uh for both you to practice safely and effectively and also for your client So thank you very much for listening Um there's a few references here and I look forward to seeing you in another lecture ________________ 2.7 Targeted Therapies and Immunotherapy in Cancer targeted therapies and immunotherapy for cancer. So there are a number of different targeted therapies and there are too many to list really on a single slide or even many slides. And there's a link here to Cancer Research UK website that might tell you about different cancer drugs and their types. I'll give you a few of the most common ones you might encounter. So anti-HER2 drugs. really common in breast cancer and can be relevant to some other cancers. And these include monoclonal antibodies that tend to end in something called MAB. So whenever you see a MAB, it's likely to be a monoclonal antibody. And they tend to be given by infusion or injection. So trastuzumab is a generic name for Herceptin, and petuzumab is called Perjeta. There are also anti-HER2 small molecule inhibitors such as neratinib and others that I will... cover in a second. Tyrosine kinase inhibitors are very common. They're used across multiple cancer types and they tend to end in IB. So BRAF mutations in melanoma, one of the greatest advances for this really aggressive cancer has been the use of bumeraphonib and then following that the use of immunotherapy. There are also other different IBs such as imatinib or Gleevec for BCR-ABL, haematological cancer, inlotinib and linvatinib as an example. So whenever you see an IB, it's effectively a tyrosine kinase inhibitor. NTVEGF drugs are the drugs that affect angiogenesis, and that's the formation of new blood vessels that's involved in the cancer process. And these are things like bevacizumab or vastin. PARP inhibitors are used in BRCA mutant cancers. or where there is a defect in homologous recombination, HRD tumours, so a specific subset of ovarian cancer, as an example. There are CDK4-6 inhibitors, which are now used in hormone receptor-positive breast cancer really widely, and these are the things like abema cyclib and palba cyclib. And as I mentioned, there are many classes, so each class and medication within the class has different toxicity, so you'll need to read up whenever you encounter this in your client. So I'll just give you a few outlines on HER2-positive breast cancer. So as I mentioned, Herceptin, Pageta are monoclonal antibodies that bind to different domains, the different areas of the HER2 receptor, which prevents... it dimerizing, so joining together and disrupting downstream signaling. And what's interesting about this is that the HER2 receptors will dimerize and promote signaling, but also these monoclonal antibodies, by binding to that receptor, promote antibody-dependent cell site toxicity, which means when they're bound, they basically cool cells to be able to mop up the cancer cells. So now quite often these drugs are given as a Fesco combined subcutaneous injection that people can do at home after the initial tests at the hospital. And there's some interesting trials around community pharmacies using that as well. We do need a baseline ECG and a cardiogram, so recordings of the heart rhythm, as well as a jelly scan of the heart to look at the heart function because there is a risk of cardiotoxicity. the heart function can be affected. And these can be given as new adjuvants, so with chemotherapy before surgery or adjuvant treatment after surgery, as an example. With metastatic disease, they usually start with anti-HER2 dual blockade during chemotherapy. And if this becomes resistant, there's a couple of other anti-HER2 drugs that we could use. And there's also a combination with small molecule inhibitors in adjuvant therapy. that was established in the HER2 CLIMB trial. So, as I mentioned, cardiotoxicity is one of the big side effects, and it's particularly difficult when it follows ECT treatment because the epirubicin EC and sometimes other anthracyclines that are used are also cardiotoxic. So usually, echocardiogram is done every three months as per guidelines that monitors what we call LVEF, and that's left ventricular ejection fraction. Basically, can the heart pump out sufficient blood? Is there a good heart contraction that happens? And exercise is important for cardiac protection, but actually there's no specific guidelines issued at the moment. What we do know is that moderate intensity exercise training and was shown to prevent a decrease. in the left ventricular ejection fraction and physical capacity during her septum therapy and her deposit of breast cancer. So we tend to suggest general population guidelines of physical activity which we've already covered in the pre-herp section unless the heart is significantly affected in which case then you would need to speak to a cardiac rehab specialist really. If there is a declining function usually cardiology referral is made by the oncology team And quite often ACE inhibitors are used in that particular setting, and there may be adjustments to treatment, so you might shorten the duration of anti-HER2 treatment depending on the case. Anti-HER2 small molecule inhibitors are the IBS effectively, so these are the tyrosine kinase inhibitors that function downstream effectively. And so the big molecules, the big monoclonal antibodies bind on the outside of the cell, whereas the receptor tyrosine kinase inhibitors tend to work inside the cell. And we normally say that a number of them can interact with grapefruit, so do remember to tell your clients to avoid grapefruit in active treatment. So lapatinib, niratinib and tucatinib are the three things that tend to be used in this particular setting. You can read about those here. Tucatinib is particularly believed to be able to cross the blood-brain barrier. and it's likely going to become the go-to option for patients who have brain involvement. The most common effects of lopatinib and niratib is diarrhoea. They're usually given a medium for that, and there can be rash and other side effects. Fasting before taking lopatinib, and likely the others as well, may potentially reduce side effects. So usually we advise taking it one hour before a meal after an overnight fast. And this has been shown to reduce the risk of rash and diarrhoea. without any detrimental effect on complete response. So PCI is complete pathological response, which is really important. And there's very early evidence of potential beneficial effects, so potentiation with curcumin, quercetin, optiberi potentially, but it's very early on and it's not been significantly studied in large human trials. Immunotherapy is really important. It's the biggest advance in cancer therapy in the recent years. And the aim of immunotherapy is to aim to lift immune suppression or to target tumours very precisely with engineered therapy, but they do carry a risk of immune-related complications. Things that are in clinical practice are CAR-T, or chimeric antigen receptor T cell therapy, and it's used for leukaemia in children and also lymphoma and other blood cancer malignancies, so hematological malignancies. We have checkpoint inhibitors, or ICIs, immune checkpoint inhibitors, that target CTLA-4, PD-1 and PD-L1. And you can have a look at the video from Cancer Research UK and I'll outline the mechanism of action in a moment. You can also use cytokines. And there's emerging things like tumor vaccines, dendritic cells, all sorts of other stuff, but it's not really in common clinical use in the UK. Patient selection is really, really important because not everybody will be fit enough for this particular therapy. And we also have to be prepared for IRAs or immunotherapy-related adverse events. So for CAR T, a CRS or cytokine release syndrome is a significant problem and in some cases can require ICU care and really trying to inhibit the massive rise in cytokines. kinds of things like docilizumab. And with immune checkpoint inhibitors, you also have to be prepared for the various ITIS symptoms, so colitis, et cetera. And there's also autoimmune disease risk that will not go away after the therapy has finished. So I quite often now see autoimmune thyroiditis in women with triple negative breast cancer that have been treated with immune checkpoint inhibitors. So let's have a look at the immune checkpoint inhibitors. So here's an Some diagrams that explain things that have to do with PD-1 and PD-L1 and CTLA-4. So what's important to realise is that certainly in solid tumours, the tumour cells will try and hide and protect themselves. So they will upregulate the expression of something called PD-L1, which then binds to PD-1 on a T cell and basically tells it to calm down and not attack. If we are trying to then use other treatments with immune checkpoint inhibitors, we can block either PD-L1 or block PD-1. And that means that this inhibition is then relieved and the T cell can then become activated and can then cause tumor cell death. With CTLA-4, again, it's a reasonably similar thing. So usually, CTLA-4 binding to B7 inhibits the T cell activation. If we can stop that binding using the anti-CTLA-4 antibody, we relieve that inhibition. So this is why it's called the immune checkpoint inhibitor treatment. And then again, result in tumor cell death. So effectively, we're trying to lift The tumour-led inhibition of T-cell response. There is a crucial role for the gut microbiome in immune checkpoint inhibitor treatment and what we know is that there is a number of different clinical studies that show that if people are treated with broad-spectrum antibiotics, quite often they will have a negative effect on the response to cancer immunotherapy with immune checkpoint inhibitors. It also appears now that PPIs such as omeprazole and zoprazole etc. administration of those with immunotherapy with immune checkpoint inhibitors was also associated with a negative impact on people's progression-free survival and overall survival in bladder cancer as an example. So we really don't want to affect our gut microbiome in a negative way. The number of different bacteria that have been associated with either a better or a worse response to immunotherapy, what's really important to know is it's really not about having a single bacteria, it's about looking at the big picture, and it's about looking at patterns. What we do know is that responders tend to have higher levels of certain bacteria that you can see listed here, so things like acromantia. and non-responders tend to have a different profile. And we can also see a different microbiome in people who tend to have immune checkpoint inhibitor-induced colitis. What we do know is that a lot of research is currently ongoing and that we really need to be watching that space. And I often say I reserve to change my mind about the gut microbiome and cancer every three to six months because the research moves at a really significant pace. pace. What we know is that if we have good diversity, ultimately, it's going to help us usually with having a beta-immune checkpoint inhibitor response. And we've also seen trials in melanoma that show 20 grams of fiber as being particularly beneficial or more. We know that we want to make sure that we have good levels, not excessive, not too little, not too much, just try the vicomancy and bifidobacteria, some examples here. And a number of things are being studied to improve the antibiotic-related dysbiosis to help with immune checkpoint inhibitor therapy. So that includes FMT, the fecal microbiome transplants, probiotics, diet, prebiotics, and even considering delaying therapy in selected patients to give them some time for that microbiome to recover. There are different trials. I'm not going to go over those, but you can look at those in the paper I've provided, and a number of trials that are being used, anything from FMT to prebiotics to very specific probiotics, mainly targeting bifidobacteria specifically. We also, apart from the gut microbiome, we also want to look at the systemic inflammation. What we know from a 2022 systematic review meta-analysis is that PLR and NLR which is neutrophil to lymphocyte ratio and platelet lymphocyte ratio, have been shown to be prognostic markers in non-small cell lung cancer patients treated with immunotherapy with immune checkpoint inhibitors. So NLR and PLR, when they're elevated, they're markers of increased systemic inflammation. We also know in melanoma there was a poorer overall survival if patients started their immunotherapy with a higher baseline NLR. And where CRP increase fast over time, it tends to be a predictor of elevated progression risk with non-small cell lung cancer. And there might be potential for worse immune-related or immunotherapy-related adverse events in certain cancer types when there's elevated inflammatory markers. So it's an area of investigation. Ultimately, increased systemic inflammation as indicated by NLR, PLR and CRP is not good news before we start immunotherapy, so we want to be able to regulate it. So what are the potential interventions we might consider? Well, medical interventions, of course, would include ideally avoiding giving antibiotics or PPIs during or right before immunotherapy, unless it's completely unavoidable. And of course, we are studying things like FMT. For nutritional aspects, we want to assess and address NLR, PLR, CRP and other inflammatory markers to make sure that people have as low a systemic level of inflammation as possible before their treatment. And we want to support a healthier, more diverse gut microbiome through nutrition. So this might include advice around incorporating a wide variety of vegetable derived fibre. So we want to aim for 7 to 10 portions of rainbow vegetables daily. Plenty of herbs and spices are polyphenol rich and support a good gut microbiome. We want to give people a target of 30 plants or more per week, which has been shown to be associated with better microbiome diversity. And certainly something Dr. Tim Spector talks about a lot. And consider judicious use of fermented foods as tolerated. So with fermented foods, It's about small amounts of diverse foods throughout the week. It's not about trying to eat a whole ton of sauerkraut all in one go. So quite often, again, Dr. Spector talks about the four Ks, kefir, kombucha, kraut and kimchi. And we might want to, in a specific case, consider supporting specific species with food interventions. So, for example, with Acumansia, you might want to use things like aronia berry or pomegranate. For the moment we would not recommend using probiotics. So recent research with immune checkpoint inhibitor treatment of melanoma suggests best outcomes with 20 grams of fiber or more daily and no probiotics. So we want to make sure we don't do any harm and at the moment there is not enough research that establishes which probiotics are best in the setting. So I would suggest not using any and doing food first. We don't really know about the results. What sort of testing we need to do, what is the role for any herbal antimicrobials or personalised regimes, we need more research. For the moment, supporting good gut microbiome diversity with food first is really essential. There are also combination approaches being used now, so things like chemoimmunotherapy, so combining immunotherapy with chemotherapy. This is the approach that's used in triple negative breast cancer increasingly. We can combine immunotherapy and targeted drugs, so lenvatinib and pembrolizumab is something that's quite often used in gynaecological cancers, things like endometrial cancer and some ovarian cancers as well. These combinations may have increased toxicity and you've got to watch out for those multiple class side effects. So when you're looking at a combination, you need to take each drug individually, make sure you check your interactions and make sure you check the side effects for each drug so you can watch out for those. with your client and then also consider supporting them. So for example with linvatinib, I'll give you some examples there, increased risk of thyroid problems, so we tend to monitor thyroid function, increased risk of blood pressure problems, so we ask people to keep a blood pressure diary at home, and hand foot syndrome, so for this we want to make sure that they're keeping their hands and feet nice and dry and clean. And also considering things like the 10% urea cream, which we tend to find very helpful with other Hanford syndrome medications, such as capicitabine. And of course, with pembrolizumab, then you have to watch out for the ITS effects and development of any other autoimmune diseases. So you can see this becomes a much more complicated issue when we've got multiple combinations and multiple classes of drug involved. So I hope you found this helpful as an introduction. We do go into the immune system in much more detail in Module 3, so do watch out for that because we'll discuss the NLR and PLR cut-offs and CRP, et cetera, at that point. Thank you for listening, and I look forward to seeing you in the next section. ________________ 2.9 Live Meeting Month 2 and you want to be able to try and complete as many of the resources as possible you know most of us will go plus and minus a couple of weeks on coures that's entirely normal but if anybody is at any point falling behind significantly can you please please let me know um in advance because it's really really important um for me to know so I can figure out a way to help Okay so we've submitted some questions so just as a gentle reminder every single month you will have a post for questions so save your questions for that post the rest of Facebook is ready for you guys to communicate with each other but I'm not going to be monitoring it for questions you could imagine that I have about a million groups on Facebook as all of you guys do so it's absolutely impossible for me to keep track and that's why there's a single post with all the questions that go underneath it and then what Emma does is then Cates it for me in one document so we can make sure we're not missing anybody and we're addressing all of the questions five let me share my my screen and then we can shout away so Sarah ask would it be reasonable advisable to use modify citros spect in either side of a biopsy as well as for surgery this one is a bit of a trickier one because the rationale for using modifi Citrus spting around surgery is a biological one not a study one we don't have a good study for it but we do know that gtin 3 which was what modified citros spectin inhibits does get significantly upregulated post ically in particular and it plays a role in Invasion metastasis now for biopsies that is not been very clearly documented so while technically speaking we might potentially have a rationale for doing it particularly for an extensive biopsy such as a liver biopsy we just don't have enough data for me to answer that question confidently because there's been not as many studies on what the Galatin 3 kinetics is after a biopsy in all the different situations so it's a little bit trickier if I've got somebody going in for a large biopsy should we say a significant biopsy I might use that but I'll will discuss the pros and cons and lack of evidence with a client to patient to make sure they understand that we actually don't know but we might be using it in a biological rationale so it's little less convincing from the biological mechanism because surgeries just got better documentation than biopsies do um blood viscosity and cancer s da was talking about would you consider strategies to thin the blood if there's no surgical interventions and is one of the meches of action on curcumin cancer is that it is known to thin the blood not really so curcumin and the Hallmarks of cancer um are very different so I'll just see if I can quickly find you a really good picture of Kirin Hallmarks of cancer because it's not really a lot less to do with um yeah let me find this one let me just try and see if I can get that for you so an image in a new tab I'll share that bit I mean there's many of these pictures you're going to see boatloads of them but um circumin actually targets vast majority of the Hallmarks of cancer so actually can you see all these different metabolic pathways from that perspective so it's that you will find them if you look for any curcumin and Hallmarks of cancer papers there's different versions of this there's many versions there's a bigger one that is much more complicated than that but the mechanis of action of curcumin in terms of cancer is actually a lot less to do with it thinning the blood although that's why you have to usually stop it around um surgery because it's one of the ones that will affect Fon um pner blood is linked to lower platelet count now Daisy explain that to me because that's not necessarily true so can you just explain the rationale from that side um I was just reading the block book really and um there is a connection between tin and blood and potentially lower platelet count although that's not always the case that's my understanding yeah exactly and it's important to know that it's not always the case so ultimately in terms of blood thinning yes if you're going to have a really low plated count the blood will not clot properly right and so we've not recently thinned the blood but the blood will just not not have abnormal clotting now the actual how prone to quoting blood is which is when we talking about blood thing effect that's actually you know your pro PT a those kind of markers they're not actually linked to the platelet count so you can have a normal platelet count and then have a blood that's either more pron tootin or less pron tootin so it's a very different it's a different assessment so you can have a link you can have an association but they're not the same things so in terms of Clum you're looking at different things is are they capable of clotting or at a higher risk of clotting so are they capable of clotting is is their PL counted normal range right so can they clot are they more prone to clot is their plate count higher than normal range right if they have thrombocytosis they're much more likely to CL they just more plat around it's stickier blood not necessarily it doesn't follow the other way around that you know thinner blood will always have lower plate counts it's just not the same um so if I give you for example if I give you um werin or if I you're over oxan you're going to have thin blood your plate is not going to change one bit Yeah but would would the blood viscosity then be linked to better worse outcomes because technically that's how some of the agents are being delivered whether natural or chemo you know through the blood I work with a lot of lime disease clients that they get um thick blood and that's partly because um of how the bacteria Works to thicken the blood so protect itself from antibiotics and things like that so just wondering whether May there may be the same mechanism in cancer no because actually we definitely don't want lower plate counts because the bleeding is definitely going to be problem not not relation to PL to but um maybe lower fibrinogen yeah we want normal not lower so we don't want we don't we want everything within normal range so our whole game with cancer in general is to keep everything within homeostasis range right so that means we need to keep everything within normal range so having a platet count of 100 is not any better for you it's actually worse for you than having a platelet count of 150 within the normal range right so they you wouldn't want to go for lower you'd want to go for normal and again different patients will run at within normal range at a different level okay from that perspec their Bas lines might be slightly different so you definitely don't want High plat thrombocytosis which is quite often reactive to inflammation in cancer okay so surgery or any other inflammat trigger including cancer-driven inflammation with r stess we definitely don't want that that's not good we definitely don't want High fibrinogen that's again a qu sequence quite often of the inflammatory process so not going to get rais fibrinogen in and of itself it's usually associated with rais inflammatory markers so the aim of the game here isn't so while you're going to consider the clotting bed the aim of the game is to unplug the mechanis that drive the clotting which a lot of the time is actually inflammation based so you need to kind of almost we need to take a couple of steps steps back now if I do have a patient with high fibrinogen and thrombocytosis I might give them as long as there's no other contraindication something like nines um to be able to support them to reduce the risk of them clotting because they are abnormally high at a high risk of loss and don't forget anybody with active cancer no matter what their platelets are no matter what anything else is is in automatically proclotting State because of active cancer that's why we always warn patient about dbts and PS and all of the signs of that because they are much more likely to plot automatically okay so um yeah so I would say do I but do I include the fibrogen all the time no but I am always going to be including inflammatory markers and if they're inflammat markers are raised there fibrinogen is either top end of normal or abnormal I can guarantee you that there's almost no reason to run it the other reason do you know what the problem is with running PT and fibrin practically is with most patients no so no that's why and that's why it's a good thing to discuss it practically that sample has to be in the lab within six hours otherwise it's not accurate so you cannot run a clotting unless you're going to have your patient attend lab and have that sample analyzed within six hours so you can send if you can send them to TDL or any of the other blood Labs that will take blood sample analyze it you find you can't post it okay you can't have a Transit time say for example you know if I I'm in reading and I'm sending it to a lab in London if there's traffic on the M25 and they end up being delayed sorry that sample has to be chucked out it's just not accurate enough you have a six-hour window for clotting so running PT and fibrin on all my patients would be impractical a lot of the time particularly those who live in the middle of I don't know maybe somewhere like iness or middle of rural Wales because trying to get them to somewhere that can run their bloods within that lab time is quite tricky for some of my patients um homocystine has the spinning problem so you have the centrifuge is a problem now again if I can have it great am I going to worry about it terribly no because if I have the oat if I have the MMA and falo I can predict roughly what the homosysteine will be if I have the B6 B12 and folate I can tell you whether that hyem is going to be abnormal or abnormal right I don't actually need to have the value it's great if you can do it but I think always think about I guess what the practicalities are and also how much stress we're putting on cancer patients to do so certain things you know when they're already probably exhausted from running around between different blood tests so you can still do decision- making without it necessarily but um but yeah clotting is very very important in cancer it's just lower is not always better is how I describe it and then you ask a question about gen genetic testing what kind of genetic testing do you mean so genetic testing uh obviously there's the BR jees there's the p53 that I've come across there's different uh you know I think there was one for prostate cancer um there's probably a lot that we don't know about genetics and cancer yet but there are some known ones and uh I was just wondering whether how much of it do you do and I know there's issues associated with genetic testing and counseling afterwards because people tend to think oh I'm going to get counsel now and you don't want to freak them out if they've come to you for preventative stuff so I was just wondering do you do it where do you do it what kind of training do you get you do uh courses on genetic counseling would you recommend us do courses on genetic counseling if we do do genetic testing in our practices you are not permitted as nutritional therapist to do any hereditary cancer testing I'm afraid okay out of scope it's a medical test if I tell you you've got braa one and you're going to have to have a double miste to and have your ovaries out you're not going to be very pleased with me as nutritional therapist trying to make that decision and you you you guys just don't have the medical followup that would require to action the test so if I have a tp53 mutant if I have a Le syndrome on my hands I have to AC in a whole program of medical followup including whole body of my eyes including scoping you know up and down Scopes to make sure they don't have any current poignancy there's so much medicine that needs to go on around those patients that that you would not be able to action therefore it's not appropriate for you to run a test that you can't action the results of that's why you are not permitted to run tumor markers and you should not be running any any braa testing because you're going to so I I'm pretty sure I've seen on the BN Forum um neutr gentics you can WR the come home but neutr genetics is different but not MediCal genetics so what we talking about here braas yeah and and you know p-53 they are really significant conditions that will completely change somebody's medical course of treatment and you so neutr gentics go right ahead because does it does it give you medical diagnosis okay no does it give you a medical followup no this is completely within your scope of practice no no germline genetics for cancer patients unless you have a doctor's involvement and okay even I myself depending on the on the the amount anyway the amount of basically medicine that has to go on around this is actually significant even for me as a GMC registered doctor which I do run those tests but like if I find a pb2 check two mutations it actually might change somebody is cancer treatment I have to be able to go off and talk to the oncologist and say you can now potentially put them on a par inhibitor you just wouldn't there's just no followup from from your side that you so yeah I would just not touch it from that perspective um but yeah neutr gentics go right ahead and obviously you would have had different courses and different training on that bet um melatonin is absolutely does have a benefit being used wrongs side radiotherapy there you can find multiple reviews in the mechanism not um there's not a lot of clinical data um I have to say though a lot of my patients are melatonin and I have no severe radiation dermatitis with my patients so anybody who's melatonin and literally see nothing above grade two probably grade one grade two is maximum we get from radiation but how high are those generally you wouldn't again it's out of scope for you guys so yeah that's what I'm aware of and I'm aware of that the GPS can prescribe but they wouldn't prescribe the 20 milligrams that are being talked about right yeah no you wouldn't so usually it's an integrative functional Doctor Who would prescribe it so we prescribe it in clinic yeah it would need to be somebody else would you just do prescribing service then for some of our clients down the line um we well we good question so we have a nurse prescriber who will be opening a service it will obviously depend on what what the referral is like so we have referral criteria so even for our own internal enties we have referral criteria but we have a nurse prescriber who's going to be doing a service for things like refaim and melatonin maybe LDN and things like that uh LDN is is is slightly tricky because there's there's definitely considerations some patients can be quite sensitive to it but for the moment he will be doing that and then at some point he'll be doing motto therapy as well so at the moment we offer it as a medical service if that makes sense as a full Integrative Medicine service rather than a separate one but it certainly will become an option more when we've got more capacity just because our doctors are not really busy at the moment but um I would say to you though however is that any dose is better than no dose so from my perspective even if they get two or three milligrams from their GP to support their sleep and generally support them during radiotherapy it will still be better than not getting anything so the problem with GP prescribing for it is what you will find is that unless a fit GP prescribing criteria which has short-term use in patients over 55 okay you're going to struggle to get a GP toon they're very happy to we are very happy as Medics which is ridiculous prescribe very addictive drugs like Zone them go God forbid I ask you for melatonin I mean look at me like I've grown horn so in interbus of medicine we all laugh at it because it seems completely ridiculous but it's a familiarity thing a little bit like yeah Becky I'm not surprised you DP said no I'm afraid you're not over 55 and you do not have short-term insomnia problem so there we go yeah or you don't have jet lag or whatever other crappy in I mean it is ridiculous but yet guess what happens when you go on to most medical ward rounds you know that's what I used to have to do as a medical doctor in medicine oh the patient has trouble sleeping for the last three nights prescribe them some zop well why don't we just prescribe them some melatonin but anyway it will change at some point unfortunately we're not there yet but we are much happier prescribing VAR so would prescribing phaces be able to do that something like Dixons in Glasgow no I don't know you need to ask them uhuh okay but again don't forget they need to they also if you are sending them to anybody other in a medical doctor they need to tell you they've checked all the drug drug interuption they can cover you from that perspective that's really really important they should do but they need to document it within the letter so that's what we do always we check drug drug and Drug supplement interactions but you'd be surprised how many people are very happy to hand out those when they don't bother doing that yeah thank um so yeah uh and then we've got nutrients which are really interesting questions so nutrients is so in terms of anything contraindicated with most cancers I mean there's nothing that's contraindicated with most cancers there there's things you have to be cautious with is how I describe it um and tell me about B12 in cancer and MTHFR Daisy I was not sure I could see the connection there um I think I me I meant B9 probably um I wonder if you meant mtrr rather than MTHFR yeah sorry yeah so I think with with B12 um with B12 cop well B12 basically is usually elevated in a number of different cancers okay so if you're going to find if you have a p if you have a patient client in general who has no symptoms but has a persistently elevated B12 um and you don't know where it's coming from and it's definitely not coming from supplementation overuse dietary wise we need to be suspicious for malignancy because vast majority of those patients will end up being diagnosed with a cancer in the next 5 years w I don't find B12 testing reliable on its own anyway I always not reliable but but You' got to remember the mechanism for it is the fact that from the B12 perspective it's covered in the blood Force anyway but the there's two mechanism for it one is the fact that cancer cells and also some of the inflammatory cells that involv in cancer can increase B12 binding protein so you're going to hold more B12 in your blood for for this it will actually be accurate it's not about B12 action it's about the fact that your total B12 Rises because youve got more binding proteins um and the second B is of course if there is any liver Mets or primary liver cancer B12 is St in the liver and of course if there's tissue destruction you're going to get release of B12 from its store from that perspective so we don't want to over supplement B12 anyway from that perspective because higher supplementation B12 has been associated with worse outcomes in patients on active chemotherapy with cancer and the same for ION and ion is pro inflammatory however if I've got a B12 deficient patients with cancer guess what I'm going to do correct them to nor I am not going to prescribe 15,000 of ridiculousness which is what most supplements are out there at the moment but I am going to correct them into normal as according to MMA for my side of things so that's what I am going to do so doesn't it's not Contra nothing is contraindicated if they've got iron deficiency I'm going to guess what first of all trying some of the other basic interventions I've outlined in the the troubleshooting lecture but if I need to give them iron I we would give them iron some of my patients in Platinum they're going to drop like a Stone from the hemoglobin perspective you know guess what sometimes they will need either an Iron Infusion or a blood transfusion because that's what is indicate from that perspective but what we don't want to do is the the sort of the which you guys won't do but the The Lazy work that sometimes gets done in patients with cancer relate anemia is that people will go oh they're anemic let's give them iron I'm like have you proven they're iron deficient because it might not be iron deficient it might be B12 folate it might be just anemia of chronic disease from that perspect Factor yeah exactly be so exactly what Happ to your post exal so depending nothing is contraindicated but the inance you have to be cautious of is not over replacing B12 not over cooking the iron and correcting iron deficiency I you correcting always to homeostasis always to normal not superphysiological levels not 15,000 per of B12 okay that is not actually helpful in any way shap or form and if you look at a lot of M nutrients their B12 to folate Rao is so crap think about your B12 and F Cycles in the interlocking Wheels if I give you 15,000 of B12 and I give you 50% of folate what's going to happen do you think it's going to be helpful for methylation no this is utterly imbalanced one wheel is spinning like that and the other one is like so we need to also think carefully the whole B12 High B12 craze out of the US came out of the US I know ages ago and we're still not recovered and so we tend to use things like the CL Labs or SFI Health now B complex um Plus or multivit sorry B complex or multivitamin something I can't remember now what it's called they all they're all called slightly um different things I'll show you the ones we use because they have a better B12 to folate ratio um so this is the one we use when patients are off chemotherap off chemotherapy we use this one sorry me just find it I just want to show you the B12 that I tend to normally use as a level for now and then you can always correct upwards but don't don't start high so this is the multivitamin complex that does have antioxidants in it so therefore we'll use it post chemo usually but in terms of nutrition look at this B12 to folate ratio okay versus most of the stuff that you use okay that not not you personally but the the industry uses you know is ridiculous if I put now let's compare this to yeah one multivitamin CU you guys know what's going to come out it is not a fun place to be let me just find a rejector go away there's my little one here we go oh mean one with iron you're not even going to give hopefully as an automatic thing okay so let's think of this we got two you got 20,000 what do we think of that as a really good ratio for methylation mean it's not doesn't mean it's might not be helping isolated cases please don't use it with patients with cancer it's really not helpful for anybody how about copper is it the under Genesis link yeah it's a zinc to corer ratio that's more important and I'll just quickly show you the B complex that we use the B complex is the one that we use during chemotherapy um SFI it's important the plus bit is important because it will lead you down the right path hopefully let me just find it I want to show you this one cuz that's quite helpful for all of those neuropathic inducing Agents come on here we are just check it's the right one yes it's the right one so that's quite again you can see it's not it's a nearly one to one ratio it's reasonably low B12 from that perspective higher uh B6 so again thinking about the ay inducing drugs you know all of your taxines and your platinums Etc so and there's no antioxidants added it's a PB complex so I can actually use it during chemotherapy without having to worry about it well if somebody's on the copper coil like many people are these days non hormonal coil would you measure copper levels and you compare I mean I generally try and know copper to zinc ratio in as many of my patients as humanly possible because it's not the copper in of itself it's copper to zinc ratio so have having a high copper desinc ratio tends to encourage metastasis more so and as we know it's a seesaw so from that perspective just knowing copper is not enough information you need to know the Inc level as well and so I tend to use things like the comprehensive toxic and Essential Elements which is a blood and urine uh so dry blood SP and urine because it kind of gives me an overall kind of mineral status and it gives you a good Corp DES in creation can kind of see where you need to shift them is it that you actually need to supplement zinc because the copper will get shifted with zinc supplementation anyway and they're zinc low and copper normal or because otherwise that copper mid-range doesn't actually tell you anything it doesn't tell you how to intervene do we need to reduce copper intake do we need to increase zinc you need to have both bits of information to be able to tailor your your approach to that and I was very interested about Arginine and breast cancer I don't know you well I mean again there's no so when we think about amino acids the amino acids um restriction oh I love Helen sorry I just said to love the Helen Helen Peres comment when the US sneezes we catch their cold y I'm completely with you that's an excellent comment um so yeah the um with Arginine or with any amino acids the amino acid restriction bed you've got to remember that compliance is a serious issue and also you need to show me a prospective trial to show me the amino restriction amino acid restriction in humans Works deliver clinical outcome you can talk about your me of the cows compound but until you can tell me that I can maintain my patients protein status and their quality of life and their healing around chemotherapy radiotherapy and surgery and can still adequately amino acid restrict them and can still deliver a clinical outcome for progression pre survival and overall survival then I'll go and restrict their argine I don't patient argine and actually most of the new research around you'll get it in your months to um of the systems approach there will be months four of this course but most of the new research is focusing Less on restrictions but inhibiting enzymes that use these amino acids in unhelpful ways so instead of IND restricting methionine can we actually inhibit methioninase that would be more helpful intervention because meth restriction is really difficult to do methioninase if we can find a good inhibitor could be a really good productive way of doing it now you can there have been trials for therapeutic amino acid restrictions but compliance you will see if you actually read those trials compliance can be really poor with those things and if you're not comp Cent you're kind of losing you're losing your protein but for no good reason effectively that's part of the problem so I would I wouldn't over focus on amino acids too much effectively unless you got somebody who's gotten a really excessive protein intake I would focus on making sure you've got normal moderate protein intake to cover their requirements during chemo radio Etc um and then if something comes out that can show you clinical benefit and can show you it's doable workable feasible and you can restrict your without compromising the whole human I'm all for it but at the moment I haven't come up with anything that's that's useful now outside of as I said clinical trials where all of patients food is provided for them so if you're willing to provide your patient food make sure they 100% apply that's the practicalities of it you know people can talk about meccas all the time but I'm like show me show me the money people say to me oh yeah this patient have a ketogenic diet sometimes we discuss in MDT and I go okay so tell me how this mother of four who's a single mom is going to do a ketogenic diet and still feed all four or 30 kids just go ahead and tell me the practicalities of that we got to think about it a little bit right in terms of implementation um then onav viruses triggers for cancers to be honest this is something you can read up on viruses were covered very briefly as part of the causes of cancer anyway um but we because there's no specific interventions because once the Cancer's been triggered you really are looking at cancer control not just viral control you really down that path where of actually supporting the cancer so if you've got an EBV triggered nasal carcinoma you now need to treat Naser carcinoma the EBV bit is important but it's not going to cover your whole bit effectively but I was just thinking with reoccurrences going back to kind of what potentially is the root cause um because I think it was it I came across I'm not 100% sure I think it's HPV for some brain cancers even some quite aggressive ones you can be some sub ties but again thinking about it overall what we would do is we would look at as a potential potential root cause but we all infected with all sorts of interesting viruses right like probably vast majority of us had evv we all have different reaction so you actually being able to look at the cancer in somebody's immune system in immune control is always going to be more important than trying to go hunt down to the end level of the virus because if it is HPV driven guess what controls HPV in all patients their immune system what what determines whether you can or cannot clear the HPV is it the virus or is it the immune system it's the immune system so from that perspective our direction is still going to be very much in supporting the patient not just worrying about the virus from that perspective um but yeah there are definitely o viruses and you can yeah definitely read up about them in specific cancer cervical cancer obviously mopia carcinoma burkit lymphoma you know depending on which cancer you're working with I mean you could you I could spend another course talking about viruses and bacteria and everything else that causes cancer M but that's just something for you guys to investigate and then uh you asked what percentage of patients come to us for prevention and if a relative has had breast cancer and maybe they want to do um some preventative work so um our good question so my practice nothing because I don't take those cases mainly because from our perspective we are super busy with active cancer um what our nutritional therapists will see sometimes is they will see some preventive cases um probably we see most of them on the Women's Health side versus the cancer side because usually the integrative oncology side will take active cancers but a lot of our Women's Health um entes and doctors might see somebody for some preventative work so there's definitely a proportion of work to be done there no question okay um and the more prevention we have the better it is full stop so that's where we need an army of all the our trying to work on this and then there was a question about braa one two what's our views of el myectomy the bra one or two Gene positive does depend of family history by genetic expression um obviously you know it's out of scope for you guys to discuss any surgical medical treatment um the thing with bracka one braa 2 is really we have very solid data on exactly what the percentages are for cancer it doesn't mean everybody gets breast cancer and it's really up to the individual which is your genetic counseling MH down and say for your specific bracka variant here's your risk of all the different cancer not just breast so forget yeah the other cancers that come with those your Brack prostate and Brau and all sorts of other interesting things so you the genetic counsel would sit down with those patients and will'll talk them through all the different cancer risks and usually then the oncology team would get involved in managing those as whether it is Imaging surgery other follow-ups you know if you've got Lynch syndrome there's a certain amount of followup that would need to happen so mastectomy non mastectomy is a is something that gets discussed with a patient that point based on their specific numbers of exactly the mutation they have and then they choose ultimately from that side so it's not really anybody's view it's the patient view of what what they want to know bracka one and bracka 2 obviously have quite a different profile so you can't mix the two together in terms of cancer predisposition so it is important that somebody gets individual counseling for it but given the fact that this we're talking about tissue at risk the tissue most at risk for vast majority of braa one braa 2 is a varant tissue and breast issue how you choose to manage that is really kind of up to the discussion and the numbers that you've been you've had and then some women would delay that decision they will have moniter and they will delay that decision on for surgery up until a certain point in their life so they said okay fine well I've had my children now is the time that I'm actually quite happy to have my ovaries out because the very cancer has a very very poor prognosis um so yeah it's different people doing different things U micun therapy for cancer um so D says obviously she's using it in other conditions and and appar it's used in in Europe and there's no studies there's not a single study that I can tell you guys that we would do it so from our perspective we don't use it in clinic and or would I be able to use it because I've got no evidence to offer patience as to what it would do and actually we don't always know whether we're doing harm or whether we're improving outcomes so until somebody publishes something to say that's what we want to do then I would apply extreme portion to any intervention because sometimes what works really well in normal population is not going to work very well in patients with cancer who have very different physiology on treatment so that one I cannot answer you because there's no evidence MH cancer stem cells uh will come with them that in your or so we'll do that bit and then protic enzymes um oh gosh this this this is a really interesting question so there's this massive protocol of prootic enzymes of like I don't know how many tablets 60 tablets a day or something ridiculous from some doctor somewhere um basically you're not able to eat because you taking so many protic and tablets um and apparently there's some cases and there's no really good Publications on it anyway um my view of protic enzymes is I use it like I would use it in normal way so I do use Broman for example as an anti-inflammatory and to clean up some stuff post-inflammation post surgical inflammation other bits and pieces but in terms of excessive dose uses I just don't see there's any good evidence for using excessive dosing of prolistic enzymes and I was just wondering whether because I read that some antibiotics are being used for certain types of cancers then I was thinking do you some cancers form biofilms is there a mechanism as well that may be at Play no okay they don't BS now don't forget all of the cancers have their own microbiomes and I have but cancer cancers cancers themselves do not form biofilms because human cells do not form biofilms they just don't have the synthetic mechanism for it from that perspective so I think it's really important that we we think about now the reason the reason antibiotics can be used in this because the antibiotic also have anticancer effects those particular ones not any random anti biotic it's actually some very very specific ones so if I gave you foamin you're not going to use it as an antic cancer treatment it just doesn't have the mechanism of action to be able to beat cancer so it's a bit different yeah enzyme yeah absolutely right so Becky said she's had good good um outcomes for neuropathy but again that's what I'm saying we use it for specific things so we use it to reduce inflammation maybe for circulatory benefits for other things like that but there isn't this I this craze for trying to feed people protic canens rather and food oh no no I wasn't going there I was just wondering I know you weren't but you will see people who will go there my lovely you will honestly the one of the one of the crazy things about swimming in this particular Pond is you will see people say all sorts of weird and wonderful things and people nod and smile and you're like why what what where is this craziness coming from but yeah for said Bray I use quite often I can use combination enzymes again we use cepas quite a bit use nines I think cipas we can't use them and yeah you guys can't yeah and we we can use it yeah um but I think things like you know things like Bray and nine is are not infrequently used depending on what the indication is um from that perspective and um and thank you Becky for for your experience always really useful chronotherapy chronotherapy or time chemotherapy offered in the UK would do you think the answer to that is probably not but I thought it's a great idea I mean the research phen noral chemo Daisy I love you the fact that you're so optimistic to think that we can even try and put time people absolutely not I can barely get patients into chemo and radio on time you know to actually have a therapeutic benefit in in the moment on the NHS because they were so over stretched and the situations is getting worse and worse and worse it's not going to get better you know think about cancer burdens you know you've probably seen the recent coverage around breast guns in particular um so and chromotherapy is pretty much never going to be an option outside of the private care setting in the UK I would say that's important the other thing is we barring a few observational studies very few people have done I haven't seen any good prospective randomized control trials so you've done we what we've done is we've done compared groups of people who had chemotherapy at this time versus group of chemotherapy at that time for example morning versus evening okay we know for some blood malignancies that might make a difference to survival but we've done it in the other way we've done it as a retrospective analysis we haven't actually put two people in the groups randomize them and said is this definitely better than the other thing and this is the only difference between the two groups so until they run some really good chronotherapy trials and we figure out for What patients what cancers What treatments at what exact times we won't be able to answer that question so we once you've got the port as well you can do sort of micro doing of chemo rather than having the mega doing which may also have some benefits according to that's metronomic that's different so um so Becky chronotherapy is metronomic therapy is slightly different 48 hour pump is not unfortunately chronotherapy it's because it doesn't change with time of day chronotherapy should be able to be timed to a a 48 hour pump is just basically the way that you have a f Fox for Fox Theory and everything with fall for a starting point um but um chronotherapy is actually timing so saying patients on with um cancer XS on treatment wise have to have their treatment between 8:00 to 10: in the morning because that's what delivers the best outcomes that's how precise you really need to get to that point um when we're talking about what was your last Point Daisy that I wanted to cover that you can have the in terms ofis as well which is that's called metronomic dosing so that's completely different again it's not chronotherapy it's just it's lowd dose therapy so my understanding is once you have the port you can do either right it's just setting up the time it always said okay I thought you've got the port you can be S at home watching TV and okay I I sincerely hope Nobody messes with their pump at home um at any point I mean don't because this is going to give me nightmares no no so and and nobody should be adjusting any of their dos of chemotherapy so it's all adjusted by the oncologist metronomic lowd dose therapy is used in certain cancers there's a reason for why metronomic is not standard of care it is not as effective okay for vast majority of patients kind of to the body but in terms of me saying if I compare the effectiveness of ECT versus metronomic cyclophosphamide in metastatic breast cancer they're miles apart miles apart from the efficacy perspective so there's a reason for why we give high doses and that's because of therapeutic Effectiveness but when we need to be kind to the body for multiple reasons and we just need to be able to give a line of therapy to either debilitated patient when we need to be kind of for other reasons then we can give metronomic but it needs to be decided by the oncologist it is a very specific kind of treatment it needs to be monitored in a different way so yeah it's absolutely not your own pump adjustment from that perspective um so yes and then surgence and timing of breast cancer linning with cycle there's actually no consistent relationships so I know Dr block says it I can tell you if you've done any your your own research that's what we say there four systematic reviews reported there's insufficient evidence to determine if any phase of menstrual cycle provides a favorable outcome and if you're looking at the data one study says fcul is better the other study says Lal is better one study shows no effect I mean it's it's a really messy area there's no actual strong evidence for one menstrual cycle so therefore absolutely you will not ever get a surgeon waiting to remove breast cancer because there's insufficient evidence to say where exactly you were supposed to be removing okay thank you so much so many questions I appreciate I love questions you know me I I actually really enjoy questions uh so Mel asked about the whole body MRI um so again out of your scope Melody because you know that because otherwise you're going to have to action the effects of a whole body MRI which is never going to happen um but yeah there there is a scope for it from the medical perspective there has to be a medical referral usually from that perspective and there is a place for it for particularly high risk patients um more in the preventative setting um that's really really useful if you have a patient who's got active cancer and they normal followup we should be using normal Imaging that standard for their kind of cancer so for example I don't know if I want to look at metastatic Nona lung cancer what I might be looking at as a high resolution CT plus pet you know as an example if they've got metastatic disease whole body MRI is kind of neither neither here nor there but for preventative side of things looking at High high risk populations it can have a place the the con the con bit not only the cost of it from that perspective but the conb is don't forget you're going to get a lot of what we call incidental omus and that means that you and I all of us here have weird lovely lumps and bumps on the inside that we are completely unaware of and they mean nothing they mean they yeah they mean nothing but you're going to worry yourself to death that that 1 cm fatty lump sitting somewhere is now cancer and you're going to have to undergo extensive investigations to make sure that that lump is not cancer so the problem is a little bit like the prostate BET right the reason we don't use PSA routinely is we've become are we going to give all of our poor patients with benign prosthetic hypertrophy prostate biopsies no we're not that's a really bad idea so it's a little bit like with whole body MRI I often have quite an extensive counseling session with somebody to say what we might come up with is something useful might also come up with something that's an incidental that wouldn't have bothered you either way that will result in additional worry yeah that's what yeah I'm thinking health anxiety Then you get another issue don't you yeah so there's there's pros and cons for all of this and and so and it depending on how anxious your client already is you know you might also be thinking about okay well they might need to go and speak to somebody before they consider that full body M properly um so yeah there's there's always pros and cons um because the problem is problem with any Imaging like an MRI all it shows you a structure it doesn't show you what's inside the structure start looking at a box and saying I've got a weird box in a different place well I can open that box and find a tumor I can open that box and find a load of s fat that is just there and there's a funny fatty Lum that's about it cool uh but yeah interesting definitely and then Gabriel Gabrielle ask about um oh see1 B1 my favorite topic I do love my S1 so patient l CH te estrel and PES is um does she Gabrielle does she have her uterus still yes she does so she presumably also in progesterone yes yes um um estrogel is that just estrogen only I think it's is it both no no no it's just so no no all your horses no okay if she's got her uterus she must be on a progesterone so she needs to be on yeah she needs to be on a micronized progesterone yeah though because otherwise she will be literally sitting that for breast cancer from that perspector with the sip1 B1 in particular yeah so if she's got a p SI one B1 and Com or Andor com and or yes she does Andor mnsod Andor gstp or gstm risk of HRT for breast cancers higher than the general population we discuss that bit yeah but what what is done about because her doctor just put her on this and and I see a lot of doctors just sticking them on HRT even though they have this genetic profile yeah so um how do I how do I um we are terribly misinformed about anything to do with personalized risk um Management in medicine um so the way I prescribe HRC is very different I do prescribe HRC um is very different to how most people will prescribe HRC so I say minimum she probably needs a Dutch and she 100% needs to make sure she speaks her Doone because you should never be given what we call unopposed estrogen ever ever even param menopause I don't care when without progesterone to oppose it reason being is that what happens when you give unopposed estrogen to endometrial tissue the wound tissue what you get endometrial hyperplasia in neutal cancers right that's also the reason that continual lack of progesterone um or bumps in progesterone is also the reason why patients with PCOS have increased risk of endometrial cancer because they do not have enough of their own progerin with the force of their lifespan to protect them from the unopposed estrogen so nobody with a womb so poctoy they say you don't need progesterone I will argue vly with that U the only other time there might not be given a progesterone is if she's got a marine aquum that's the only other thing Gabriel can think of that you know what I think from memory that might be the case in which case have progesterone on top of that because the marina is in demetrial lining will be protected of laser so so should she's concerned if she should you know should she be on HRT in that case so I would say it's probably worth speaking to somebody from the kind of Integrative function perspective can sit down and do the show her some of the studies and then she can make an informed decision and then doing a Dutch for her anyway cuz that's something you can do you can absolutely optimize us anyway um what we do know is there are several studies around certain Snips so let me find you one here just put the to of my head I'll find you one all those my fun snaps so here we go so this is an interesting one so this is just the mnsod one as an example uh so this was in significant interaction for the m& sod but um so in women for example U Can so interaction with long-term HRT so risk of breast cancer versus longterm versus shortterm with decreased AC in patient with homozygous for the wild type and increased when you have the abnormal ones um there's some others is is this one so this one is for this one was for gstp one you'll find loads of these I know and then yeah and then you will usually when I count so women on hrts and we will sit down we'll look at what their genetic profile is we will actually look at the data and say okay well based on the data we currently have available from population studies your average breast cancer risk is increased by factor x whatever it is maybe three-fold or sixfold yeah and we then look at okay how do we mitigate that do you want to go in HT do you want to try one hormonal options here are all the different options if you want to go in HRT how do we make sure that we Ser you monitor you to make sure that the metabolism is as normal as possible while this can never guarantee because nobody's done a trial that it will reduce your breast cancer risk to Baseline yeah that perspective so and it's about then you know having a really fank discussion and a little bit like when we discussed the ra one management it's the person making decisions that they're comfortable with to say oh I'm because my know my risk is threefold I know that I exercise well I don't drink alcohol I will happy to be monitored serly by Dutch I understand that's not going to give me full protection but I'm happy to give it risk because it controls my symptoms so beautifully I feel great on it fine there will be other people who will say in exactly the same numbers oh gosh no I possibly couldn't have it my mother had aggressive breast cancer you know I couldn't possibly even think about that I would want to stay at Baseline risk and I definitely don't want HRT what are my other options so it's just about laying out all the information but you're absolutely right I mean to be honest it's also very dangerous high dose HRT prescribing practices have been highlighted before they problems with pre-cancers or cancers so I'm seeing quite a lot of this as well and and these women are going to HRT experts yeah experts is the loosest term my lovely these are these are doctors that specialize in in women's issues I know I know know and it's conning I know that does not guarantee I mean my the I will again just being super duper honest I don't think there's any indication for for high dose ultra high dose estrogen prescribing in women I've never had to go I I think I've had to go once above license days and that wom woman's estral blood estral was very very normal it just was not absorbing so she literally was not absorbing but Hast was I the highest I could get it to was like 220 right so that's the normal normal EST thank you very much whereas if you see from the other clinics well you're going to see 2,000 plus estrad sometimes yeah yeah healthy postmenopausally you tell me whether it's Health have that estr I mean premenopausal that's a pretty honking estal full stop and it's probably would give you all the estrogen dominant symptoms is in premenopause post menopause is an utterly inappropiate level have in the body but that's my opinion anyway can I ask you just a very quick question as well um you know the TDL um profile they do hormone profile for estrogen of the Cy measuring the cycle can't remember what it's called actually now but it says to um take the blood on the 21st day of the cycle and recently there we had a doctor here who said no this is wrong it should be you know literally during the cycle and I can't now remember yeah but uh this is this just a standard no well so you go remember when we order test we have to have a question that we want answer with a test so when I order my test for the video TL phase which is what you're talking about with day mythical 21 which may not one but it's at any point of somebody's midal phase so it could be day 19 it could be Day 26 yeah but midl tells me I want to know is the has the woman ovulated and I want to know what estrogen to Progesterone ratio is in that phe that's what the answer that that so if estrogen to Progesterone is 10:1 or around about there it's roughly normal estrogen to Progesterone ratio if her if her progesterone is less than 30 to 35 she's not ovulated right she's had an ovulatory cycle so it gives me all of that information from that perspective okay now when I run the test during periods that's day two to three when I'm looking at that I'm here looking really mostly at LH FSH I already know you Easter die in progesterone there's no point in measuring those it's it's kind of I don't even need them necessarily okay but I'm doing that because I want to see your lhf sat PCOS for example um and I want or I might have other reasons for measuring that when we measure has a defined question and answer to what I'm trying sorry it was a bit of a half bit question gener really so no it wasn't wasn't because I do order both but for specific reasons so for example in in it may be that you looking if you're looking at a PCOS presentation you you could actually do both reason you could actually say yes I want your L hfsh within that day 2 to3 because that's a diagnostic tool that's part of the criteria for PCOS but I also want to know within that cycle have you ovulated what you eatting in which case I'll do another sample at that point Okay so it it depends on the question obviously on you're no longer cycling and therefore you can just do whatever do thank you it's not half very important one and there's also lots of misunderstanding even among doctors when you could bloody measure hormones depending on this this is what I'm I'm seeing I mean it's you I can't get a straight answer because I work with a lot of doctors here and I can't get a straight answer they're all kind of on a different about Paradigm yeah and then you don't and the thing is like when we when we ask patients to go for tests like there's like a half a page of instructions of everything that have to start stop or or take at a specific point like they have to continue their HRT normally if they have on transdermal their blood set should be roughly about two hours after their transdermal testost leas or whatever it is that they're taking um but you know we give very precise instructions because what I'm measuring is I have a specific question I get it yeah you would definitely not necessarily find that everywhere okay need more training more training Bicky asked a very interesting question about HRT and bowel cancer so yes um few papers in that one What mechanisms at play um and clearly this L beneficial in all cases why that may be so ah I wish I had researched to answer that question Becky but um what I would say to you is that hypothetically we think that estrogen uh in particular can exer in in the right setting can exert some anti prol ative effects on the colonic cells in the kind of adoma adoma caroma sequence when you're kind of starting to slide off um so have they proven it no that's what they're hypothetically saying that it might be in research but the full mechanism is really not determined so actually you and I are in the same dark about this at the moment they just said well potentially there might be some estrogen response and adenoma cells that prevent them that's antiproliferative to them becoming an Arina carcinoma an actual cancer but nobody's really figured that bit out um and again my counseling HT side of things is you know a lot of my patients who have significant coloral cancer for example may have to have their ovaries taken out guess what I'm going to manage that surgical menopause for women and and depending on what all of their various Snips are we will look at how we monitor it and how we buffer it and how we do other things um but it's also not okay to just leave people with no options so at the moment we don't know who it's most going to most benefit but I we just know it has a benefit for whom we don't know but I appli standard because HRT just because you've had coloral cancer doesn't mean it has any other effect on the rest of your breast and other risks we discuss all the standard risks and benefits and we'll look at the genetics as well thank you but I would love more research somebody do some typ research I'm actually like really well done research not crappy ones honestly make do you ever doesn't ever make you laugh than you when you have this um I'm talking to Becky because it's about about cor account say remember I know has anybody seen this Tim Spectre thing of saying oh you know we're now involved in this new project saying you there's a massive rting young coloror cancer we don't know why and and as anybody look at go can tell you why you do not need to run a massive trial for it I reckon all of us here can give us a risk factor for young onset coloral cancer in the current day and age Beyond genetics what do you think yes to take a the risk factors and switch on their head I mean yeah but but generally it's just it's really me think about everything from our early microbiome disruptions think about how microbiome gets established think about how many we little kiddos we put on ppis and all sorts of other interesting things and give antibiotics to in the first three years of their life in the first thousand days you wonder why that's have as an effect think about all of the P processor I mean honestly I was like just give me a good mathematician and existing data and I can model you all of the risk of early onset colorectal cancer you do not need to run in your trial um it's just amazing I think you you might have if any of you follow it you you probably would have seen my comment how bad does a start up for 10 I've listed like about 10 things like this is just silly wonder why jeez o open the literature and have a look um lifestyle funly enough um uh Sally asked about two weeks before and after surgery modifies respect and strong potential react with chemo only oral Sally so um don't forget modified citros spectin is going to be affecting the oral absorption of any drugs anyway so you do have to be careful with it it's a little bit like we look at phgg as well in oral meds so anything that's a fiber that can sequest a medication is going to be need to be timed well but if it's IV you're bypassing all of that mechanism so you're not going to be affecting but if somebody's an oral cyclophosphamide on oral cabine on that sort of thing then yes absolutely you need to to look at the effects from that perspective Daisy was asking pectasol for that uh yeah pectasol is the only one that studied so any the only modified setrpc in the is study is spectus all so they've GED the market and they can charge 90 for a pot which is ridiculous you do need to trate up with fosol exactly it can give digestive issues so we normally would start slow and and go up and some of my patients cannot tolerate the full dose aect assol they just because of various other GI things and in this case you just need to say and be really upfront about the fact that we don't know what the lowest you can go before you lose benefit cuz nobody's done that study we just did one study we just know that we can give it five grams three times daily and have some effect in prostate cancer that's about it um so that's another Sal question is around breast cancer when it comes to hor positive breast cancer is it the case someone would already know they predisposed once they already had the disease and the tumor's been tested um ultimately yes from that perspective you know you don't know which which kind you're going to get so whether it's is receptive positive or her to positive or triple negative it will depend on multiple different factors so from the HRT perspective you don't know some of my patients in HRT can get triple negative breast cancer they might not always get estrogen receptor positive so I had a mix I had somebody who had estrogen receptor plus and tnbc all at the same time so unfortunately we won't know what it is and what and when it recurs we also don't know or can guarantee it's going to have the same receptors so when I have a patient with primary I don't know her to positive breast cancer I can't guarantee their recurrence might not have other things or they might lose their her to so particularly in patients who are long-term estrogen receptor positive have metastatic disease what we do have is we see their profiles change over time so they can flip they can get a her two flip and the her two will come in and they can also lose all of their receptors and become triple negative which of course changes the character of the disease completely and changes the treatment of the disease completely which is why you can never rely on a biopsy that was taken two years ago in a metastatic cancer patient which unfortunately we still ridiculously rely on yeah if you asked your GP to base your dosing of medication on your two years ago liver test or cholesterol they'd look at you as if you're grow fors but we're absolutely fine thinking cancers don't move for 2 years um which is where the liquid bio IES and other Advanced tools or rebiopsy in the cancer can be really important but no unfortunately you you can guarantee estrogen receptor positive is the most common so you can look at the numbers game effectively and say okay the likelihood is I have the highest likelihood obvious receptor positive breast cancer less likelihood of her2 and least likelihood of triple negative from that perspective but you can't nobody knows um so mine was hty with no other receptors and nobody could have possibly predicted that there will be somebody the only thing they could possibly I guess the rate of triple negative breast cancers in braa patients is higher than the average population again doesn't mean they can't get er+ they will get ER Plus breast cancer as well but it's just they have a higher risk for triple negative presentations as well um so then we've got uh curcumin question on tamoxifen um so not prescribe high dose C within what dosage would be uh high dose so the and then talking a little bit about neutri lymy ratio nutritional assessments um okay so all of the hanal stuff and everything else is going to get covered in next months because that's when you're entering the inflammation zone so you can you can cover that question later on the curcumin I do not give any supplemental kcin to moxin because nobody has figured out what the lowest safe dose is they've just given one lot of oscarin they showed that it reduced endoxifen levels and that was it they stopped there so not a single sausage can tell me how low I can go doesn't mean you can't e turmeric as we talked about you know we don't take off populations of India of their normal natural diet right but you just cannot give supplemental because what you will find the oncologist will get what upset with you and you can't actually give them a um trial to tell them that that dose is safe and the other one is unsafe so it's It's Tricky but I don't tend to prescribe that I saw detox for platinum chemotherapy explain this one to me no I had no I had the bladder cancer and there was given Platinum for once because it was too high for my kidneys and my nephologist kept saying you have to have high dose sodium a lot of salt in your food just detox the Platinum from your body just wondered if that was a standard of care or something not that I'm aware of he might have seen that your platin so the way the reason he might have said this to you is that you can get a problem tub tubulopathy basically the the kidney tubules with Platinum can start leaking a boatload of either sodium or magnesium and therefore you might be losing Soul if he saw you a hyperic um he would say you need to compensate for that so it's not detoxing the Platinum if that makes sense it's actually compensated for the platinum's effect same with magnesium magnesium is really hyp magnesia is incredibly common on Platinum you have to watch that patient magnesium like a Hulk um and I quite often will preload them before they go into Platinum cycle because they will drop the Magnesium it's one of the most common uh problems with electrolytes from that perspective so it may be that in your case it was based on your blood results it's certainly not not standard protable okay and and yeah so we'll and we'll talk about the all of the kind of various bits and pieces around inflammation next time and then nicotine patches stop smoking for constipations um and why do I not like nicotine patches as an idea what do you think yes it's toxic on its own it is and what's the other problem with nicotine back to DA's Point everybody it is toxic on what's the problem it's proclotting it actually affects AA Potential from the blood perspective so you already have a patient who's a sitting duct for thrombosis and you're going to give them something that's more PR obviously it's not as bad as smoking however I will normally find other tools so we will use anything from you know EFT to other methods other behavior modification methods to avoid going on nicotine patches if it's the only way I can get them off smoking and they have lung cancer fine but then I will be doing other things to mitigate the risk of nicotine but um yeah it's not my favorite to go to for that particular reason like I said it is it is actually changes the clotting anyway hyperbaric oxygen for chronic fatigue and after cancer treatment um so uh evidence no evidence it worked for me I know I know but you got to remember that you work in an evidencebased profession so you can give absolutely an N of one evidence and we are all very good grateful for that but when you talk to patients or clients you have to give evidence so you can say there is evidence for it around wound healing which there is okay you can talk about fibrosis as well so radiation related fibrosis is another area where there is evidence for it so there's two main areas of evidence for age Boton cancer and they are the main two okay surgical healing um particularly non-healing wounds and radiation fibrosis for fatigue there is no evidence therefore you can say look it's helped me if you're willing to give it a shot that's fine if that's what you think is necessary but you know what I would say really really within your scope of practice as much as you possibly can I think it's a discussion somebody else needs to probably have um usually in hboard centers if they're proper hboard Center which means they use proper pressures they have to have a medical doctor to be able to recommend and assess for hbot if you don't have one it's probably not it's probably recreational age but not proper medic no I actually go to an MS Center charity and they don't have a doctor in there oh because they mainly because usually they're for yeah if you're looking at for most nor for most cerss who are not a cerss who are actually looking at accepting patients for for for cancer and after cancer treatment outside of the MS centers as a network um they would normally have a medical assessment with somebody who is a hyperbaric oxygen physician that would be normal that's certainly where I would I send my patients outside of um I do use a m centers but I've pre-qualified them I've looked at the the risks and benefits and all the other bits and pieces with them and yes I mean outside of I'm I'm ultra cautious with hbot because there is potential risk of of regulating ngog Genesis and therefore I will always send patients in only a faster K to ketotic State I just won't send them in any other way I do not want anybody ever come back to me saying that's actually been a problem um so there's much pressure as you can give from from the metabolic perspective better so but it nobody's under the studies and that's part of the problem then Helen was asking um if hope with fmd um now our nutritionists make it ourselves so Alena Jones for example is one of our entes she just sits down with macros she will go through it on one of the softwares and she will make a plan from that perspective so we are very fortunate she's kind of our specialist we just use her all food plans so inval to Longo's book he will talk through all of the macros on all the different days of fmd so if you want to make whole food fmd that's one option um the other option is um at some point Nordic will start selling non prolon um fmd so they've actually made a get got a contract with the company does organic for food glass jars of fmd um so obviously they have to figure out shipping CU this stuff is heavy um but that is would be the only thing I'm willing to prescribe so I don't ever give pron because I keep telling my patients do not ever have processed food so I just don't ever use prolon for that reason so therefore I can't give you compliance data Sly within my practice on prolon versus non prolon because all of my patients are ined with fmd only um it's obviously easier for people when they don't have to cook but I just can't bring myself to do prone sorry anything comes from the packet I go yeah um so you can certainly use it both I mean from that perspective I think that once you get into a routine for fmd most of my patients find the whole food fmd is very doable because they get used to doing it they can batch cook stuff they can freeze stuff it's really not that complicated from that perspective so I don't think compliance is a major issue given what we're also asking everybody else to do you know I don't think it's it's that much of a problem most of the time so um but yes some people will just say I I don't want cook and in which case they can have prolong I'm just not going to encourage it um then uh oh another mCP question we do love mCP question so Liz would to ask about um resistance to in from the medical profession recommending mCP um when there is less kind of evidence on it so from my perspective I think in in in my practice certainly I would say that you need to be very careful how you communicate at their sped so mCP in in biochemical your current prostate cancer not a single sausage can tell you that you're not evidence-based CU you actually basing it on some evidence it's not very strong evidence we don't have multiple randomized control trials but it is evidence around surgery that's where you can say look we're basing it the mechanistic evidence and I've discussed with the patients the pros and cons of it and they've decided to go for it even though there isn't a trial for it so guess what evidence is what is what is evidence-based medicine what's three legs that is composed of give me the three legs anybody we should know if we're practicing evidence-- based medicine or evidencebased healthare we should know the three legs one is best available clinical evidence right best available what is best available is it around the most control trial always or metanalysis around the most control no it's just whatever is best available so it might be key series it might be whatever it is within that particular setting second bit is clinical experience yes it is a it is a lag of evidence-based medicine third bit is patient wishes needs and preferences what we like to do in medicine is completely ignore the fact that it's a three-legged store and decide to focus on the fact that we want to do leg one but not only do leg one but only do leg one to randomized control trials but there's actually a three- leg practice from that perspective and as long the key thing is not to overclaim you know if you go in with a doctor and you say I've given this patient mCP because they going to decrease their recurrence for breast cancer after their surgery they're going to laugh you out of the house and they will have every right to do so if you're going to tell them that you're going to give them mCP for the prostate cancer site or I'm giving them this round surgery because they would like to support how would you say support their peroperative recovery all right and you leave it as generic as that and you can say I've discussed the risks and benefits with them they would like to go ahead anyway despite the fact there are no prospective randomized control Tri you can leave it as that so it depends on how much you overclaim just don't overclaim don't ever overclaim stick to I spend so much time even where there's areas of randomized control trials discussing the pros and cons and RIS and benefit so when the patients walk out of there they can never say oh this person has told me they can Kure my cancer with mlet toe right no you can't um so you really need to be very specific about what your claims are and then you're practicing evidence based and you need to be able to site what you're doing so I think that is important uh there was a question about imun calpa caner patients um what would be my problem with immunal for cancer patients anybody have any idea what would be an issue with immunal immunal is heavily way based so anybody now has any idea of why could be an interesting thing hormones C factors and things so igf1 is one of the main issues here so Highway protein use has been shown to increase igf-1 now not in everybody you know if you want to give immunocal for other reasons and you've measured the igf1 and it's normal and you're fine with it don't necessarily have a problem with it but there are definitely patients for whom whey protein and high Dairy consumption in general will push the igf1 and will push it by high and actually you reduce that I have one of my ovarian C patients who literally igf1 as soon as we took out the dairy went like that okay and it was significantly elevated after her treatment she's completed all treatment at that point but she would be a Sitting Duck from the recurrence perspective with a continuously elevated Ag gf1 and compromis metabolic health so we took the dairy out you can see the igf1 literally trickle down over the next 3 to six months into normal range so if she starts eating I can PR much guarante if start eating way protein Dairy again is going to go back up she is just that susceptible it might be that you or me might not the same reaction we just have to be conscious of the fact that whey protein has been shown to elevate our gf1 that's can I ask quick question actually too if I can really quickly so colostrum would not do that presumably but as far as I'm aware not aware of any research on colostrum raising agf One Way protein has research on that but not not Clon okay and quickly you told on there won't be any research on the CIT the B stuff because there's no human clinical trials on there it's say there 15 years of research which is laughable but no human clinical trials cow's milk it it doesn't sound great to me well to be honest I never use way protein with my patients anyway so you know but even cows cow's dairy in in you know other cancers but I'm just saying in general I just don't use way protein so from my perspective I'm probably the worst person to ask about it because I just never use it I use pumpkin seed protein or other pan proteins I just don't bother using anything to the way um from that side I think whether we do or don't have risks we don't know ultimately because nobody's running the the trials here so it's it's really tricky to we're operating an Evidence free zone from that perspective which is really difficult it's quite shocking because it's quite it's it's in the food chain already it's huge part of the food chain but actually tested there shocking but you do real think about all the crab they put in our Cosmetics that nobody's tested the combined effects of and that's been around for donks and then we're wondering where we've got young ones at all sorts of cancers including thyroid I'm like well you put a batlo of endocrine disruptors in and you wait for your Canary and the Coline gland to go off well yeah exactly your poly brominate retardant everything and then you wonder why your your pyro R is unhappy so yeah and yeah it's but to be honest unfortunately you know I wish it told me it's it surprised me I've just become a little bit cynical now where like yep that's another way for them to mess with their food chain there's many ways of that that's been done our our exposome is in a very crappy place at the moment um cool and and then the only other one was um Amy has got a late question so we're going to cover that quickly and so it was a how would you best support those when have hormon receptor posit to breast cancer but refuse or later come off hormon suppressing meds so as per band guidelines you got to remember that obviously they need to have the oncologists knowledge that they have done so right and they not just the approval but condonement should we say from that perspective because as far as I'm aware B will not usually encourage you you working with somebody who's just done refusal and the Medics are not aware okay they would encourage you to communicate and encourage your patient or client to communicate with oncology about it oncology do know um which is really important and I I'll answer that in a sec of course you do need to know if somebody's come off their medication because to change their their management and their risk assessment and how often they're going to monitor that patient because you will get excessive recover risk and you potentially and therefore you need to monit them differently okay but I would say you know from my perspective there's many ways of supporting them is just the key thing is so sometimes I get I have patients who for example endocrine therapy it's a 2% improvement over 10 years and the therapy side effects would be horrendous so they discuss with Inc just saying yep I I know the numbers you've given me the numbers I'm not happy with those numbers the oncologist will shrug and say well I I understand but on the risk benefit balance for you is too much risk based on very small benefit so that's going to then then are looking at just depending on whether premenopausal post menosa it's it's going to be an independ question Amy I wish I could tell no no no that that's fine she she did let her oncologist know so they are aware but it was just that that's fine I just wanted to double check with you that was all yeah and then once you get through the the next couple of months you can tell me that my answer to everything will be it depends because it depends on what other things are going on in her systems what uh yeah is said premenopausal postmenopausal will also depend on Management in terms of what you're going to be doing what kind of monitoring you will be doing many many ways of supporting them is just making sure that everybody's well informed and that oncology is away because if she turns up in two years's time with bone pain right I really want somebody to be aware of the fact that she's off for moment she had a estrogen POS breast cancer so they don't miss yes recurence for example so just there's a good reason for why we want to keep people informed hopefully nothing will happen everything we have had patients missed before because nobody's aware that either they're off meds or they've had a diagnosis and then they had a six months delay of diagnosis of recurrent metastatic cancer with those okay yeah cool right thank you no problem anym for anym for this time can I ask hi hi there can I ask a question um mushroom therapy has been mentioned um a number of times through the slides are we going to be covering that later so there'll be a little bit of information obviously there's bod loads of various mushroom courses out there I'm not going to give you a mushroom course alongside this but there will be some some information within the course and then you can go off and do some additional training on that but there will be some information within the immune and inflammation section okay thank you uh any more any more no all good hopefully you're excited for next month so um the The Branding will be a bit all over the place mainly because you kind of there will be some of the lectures that a little bit older some of the lectures are newer so just expect a little bit of a mishmash now over months three and four this is kind of the main content really from the systems approach will be delivered and then months five and six we're deliberately very light on content because you're going to be writing your assignment so I'm not going to be teaching you very much new stuff it's much more about MDT and collaboration work and other bits and pieces um because you'll be far too busy doing the assignment brief I would not start any work on your assignment brief until you've had a Q&A first so I would read it but please don't start any work on it until you've quizzed me because honestly just to avoid wasting any time from that perspective because I just want to make sure that everybody's really clear on the brief first so don't waste time on anything um and then the only other thing to say is I know you will all chat about assignments that's fine however what I will just generally say is try not to get caught up in Loops there will be opportunities to ask questions in the Q&A so try not to answer your own questions if you could ask me that question if that makes sense does that make sense because people have gotten into trouble where there's been pockets of cohorts which they've all answered their own questions and they went off on a completely wrong track effectively so just just ask where cuz I'm the one who's going to be marking them it's always better to ask me if you're not sure about something or if you're not sure you're completely off track from that perspective and when we go off the brief it's really really clear I try I am trying to make it as easy as possible for you to hit the marks from that perspective the times when people don't do well is when they forget the brief genuinely just remember the brief honestly it's like give me what I asked for in bullet point form and then I'm I'm know exactly what I me if you're if you're not referencing referencing is a key point you know you not show me safety safety is a key point so just as long as you follow the brief you'll be absolutely fine but the next two months are basically intensive learning then we going into the case study which is the application it's actually the exciting bit because then you get to apply all of the lectures into an actual case study good okay well have a wonderful afternoon everybody Nina can I just quickly ask you if you will give us a case study of a case so we don't have to find anything nobody find anything I'll give you one and it's because I have to mark it and I have to Mar uniformly to a certain standard therefore you'll get a case you'll have all the intake paperwork so you obviously can't ask the case questions but other than that you can just tell me what assumptions you've made but other than that you'll have full intake you'll have a nutrition lifestyle diary you'll have some Bloods or Andor Imaging from that perspective and the occasional time you might I might throw in a functional test there but usually I keep it to what you might get in NHS P good because we need to keep it really really simple and then you can tell me all about the fancy test you to do afterwards good stuff wonderful afternoon so good to see you thank you ________________ 3.1 Introduction to Systems Approach to Cancer hello and welcome to module 3 and over the next two months we'll be talking about the systems approach to cancer um and supporting patients with his diagnosis and Beyond so this lecture is just an introductory lecture and then we'll break down each different system into um different um lecture slides and I'll try and combine the two and release them in pairs use your disclaimer so my approach to cancer really draws on a number of different um disciplines from the Function Medicine Matrix to Dr nisha's work to some of the metabolic work by Dr C freed uh to Carri bones approaches um and so the key components that I have identified um through combining that and some of my own reading and research um are here um and I tend to start with mental emotional spiritual health and biorhythms because I think just as much as um nutrition these form uh foundations of health and so that's really really important to start with um because really your the progress of someone's through treatment is definitely going to be affected by that um we will also talk about healthy microbiome balance and GI function balanced immune function effective detoxification healthy circulation tissue architecture mitochondrial metabolic Health um hormone balance and and balanced methylation and genomic stability so as I've um highlighted earlier the mental emotion spiritual health um are really Central to how the person is going to cope with a diagnosis treatment and either survivorship or living well with metastatic cancer and I think that's something that we need to incorporate into our plans and U making sure the person is getting some support with that healthy microbiome balance and GI function is um as we know Paramount to human health um including cancer and we will look at Oral GI vaginal and sort of other microbiomes is relevant to the particular cases and particular cancer types and of course supporting healthy GI function is relevant in all cancers to ensure not only having good nutrient absorption but also supporting normal microbiota immune interactions which brings us neatly into the next aspect which is balanced immune function and the a um within cancer radi is to aim to decrease uh inflammation and oxidative stress while supporting immune surveillance and a balanced and specific anti-tumor response and there is a significant role in looking at the tme which is a tumor micro environment within that effective detoxification is crucial so we would need to aim to reduce toxic load in terms of air water food Cosmetics Home Products basically any that interacts with us we need to consider whether they carries toxic load and try and reduce as much as possible and promote normal balanc detoxification processes you know via the liver the kidneys lung guts as appropriate to the clinical situation the cancer type and without interfering with any medications that the patient might be on and no crazy detoxes it's really important you know the the patient who has a cancer diagnosis might be going through treatments already overwhelmed with inflammation oxidative stress it's really important not to push them further healthy circulation tissue architecture is really important so we aim to promote normal blood flow and tissue perfusion and have healthy coagulation and support inhibition of angiogenesis and that's new blood vessel formation and metastasis which is a cancer spread mitochondri metabolic Health we'll talk about a lot and we here we're aiming to reduce growth factor drivers for example I insulin igf1 look at some of the driver Pathways like p3k actm tour and there's lots and lots of them that will will cover and aim to balance met metabolism and that's you know looking specifically at autophagy mitophagy glucose glutamine Pathways wildberg and reverse reverse wber effect and um seeing how they may be potentially U manipulated or supported hormone balance of course particularly relevant driven cancers you know like your um breast and endometrial Cancers and to certain extent in prostate cancer although I'll see a lot of metabolic drivers there uh can play into others as well so it's important that we we look at that examining production transport tissue sensitivity and detoxification processes U within the different hormones and their relevance before during after conventional treatment um is what we will be doing balanced methylation genomics stability is the final um aspect of the systems approach and really here we're looking at DNA repair Pathways and their relevance in cancer so braa 1 bracka 2 which we've discussed briefly earlier Pop um epigenetic changes are actually the earliest and the most comprehensive genomic uh problems occurring during carcinogenesis and actually what we have in cancer is global hypomethylation so actually most of the genome is um has decreased methylation compared to normal and then there are these islands of focal hypermethylation whereby the promoters to tumor suppressor genes are very very heavily methylated to suppress tumor suppressor gene expression um and therefore continue driving the carcinogenesis process so we'll have a little look at that and don't forget everything is connected so of course we're not looking at anything in isolation we have assess all of these different aspects and we look to support them um together but also pick out the most relevant ones for the person in front of us because not everything will be just as relevant um so you need to assess someone using the clinical history um and using the your your own test results and um using your knowledge of the cancer type of what potential drivers might be um to determine what you need to be supporting um for the particular person so it's not everything thrown at everybody at once um it really is important you personalize your approach brilliant thank you very much ________________ 3.3 Mental/emotional/spiritual health & biorhythms so just as a quick reminder about the systems approach that we're going to be taking um and we're going to start with the foundation of mental emotional and spiritual health so why is this important in cancer treatment um what we need to remember is that Aces or adverse childhood experiences actually increase the risk of cancer so a number of um clients who my come to you might already have had a significant emotional load in their life in terms of adverse char experiences and we also um are starting to come up with some early evidence that specific cancers might be um linked to increased um um propensity for specific traumas in life so for example gynecological cancers and sexual trauma or relational traumas I think it's important to address um the sort of psychoemotional health and well-being because we need to manage fear before it manages the person and Sophie Savages is absolutely huge on that five stages of grief of um Elizabeth kuer Ross are very relevant post diagnosis you might come across all of them um so there's denial I don't want to really know anything about my cancer diagnosis I don't just just go away um tell me what to do but I don't want to know anything more um anger is quite common as well anger and frustration bargaining and that's really an internal thing of saying oh if I do this maybe I will get better or if I do this then I'm my prognosis will be better depression very common and acceptance and that's really what we want people to ideally get to the acceptance with empowerment and agency um feeling alone is really common um it's particularly common in probably um younger survivors or younger patients who have no reference for cancer so really women whose peer group or men whose peer group are just not really having problems with cancer so you know in your 20s 30s 40s most most people are not really dealing with that as a diagnosis I'm not saying it's not just a stuff on older um patients but I think we need to consider that in the 60s and 70s um there are um peers who might be going through the same process and there's some companionship that might be found within that um but um it's it's a little bit trickier for sometimes for our younger clients to turn up in the cancer support group when they were un physically and find they're the only younger person in the room Beyond active treatment we also got to consider that just because treatment finishes the psychoemotional impact um continues and survivors frequently have persistent difficulties you know fears of recurrence and psychological reactions as a physical dysfunction caused by some treatment you know particularly surgery or they might have a persistent peripheral neuropathy um or persistent chemo brain or or fatigue so it's really important to address those and metastastic disease requires a different approach to looking at sort of primary cancers where we are aiming to get clients through treatment and out the other side and really managing the risk of recurence and sending off with a maintenance plan plan for living well with cancer it requires a a different psychological mindset because you that most clients who are living with that will be going through multiple treatments sometimes multiple trials um and you know they require a lot of support because there's a lot of ups and downs with you know frequent scans and is my disease controlled or has it escaped again what's my next step so it's it's significantly wearing on on the body and mind I think something that we can really participate in as nutrition therapists and natur therapy practitioners is empowerment and agency because um it's a hugely disempowering process going through medical treatment for cancer you kind of get told okay fine you've got cancer here is you the details about cancer here's the treatment um now just come in and let us do our job and quite often when the client asks what can I do um they just get told oh there's nothing you can do just go home and rest or just go home and carry on with life and that's really not true anyway from the evidence-based perspective but also I think you know this we need to promote empowerment and agency in our clients because there is always something that you can do to improve the situation including within the paliative care setting so we got to think about the psychoemotional impact on body systems and that's where the psychon neuroimmunology comes in and we know the depression worson cancer outcomes and that psychoeducational interventions for women um with primary breast cancer have found significantly reduced rates of relapse and longer survival so it is essential that we look at it and that um support is provided where it is needed and stress of cancer diagnosis and and treatment can be associated with a number of different dysfunctions within the endocrine immune and autonomic nervous system that has consequences for resistance to cancer progression and we've actually seen studies where the HPA axis is abnormal in cancer patients so for example women with metastatic breast cancer have flatter the normal cortisol patterns and that flattened di cortisol variation actually present predicts early mortality so intervention here is important so some examples of how cancer um progression can be affected via stress so as we know um stress can affect the sympathetic nervous system resulting in secretion of the of adrenaline and nor adrenaline within our nervous system but also of course promotes um secretion of cortisol in the longer term as well and so when adrenaline secreted you get the activation of adrenergic receptors on immune cells and that results in production of of immunosuppressive molecules so like ctla4 which is one of the targets for some of the immunotherapy treatments and then simultaneously the camines which are the adrenaline or adrenaline um and dopamine can also um inhibit the production of important activation cyto kindes such as interferent gamma and il2 and il12 so what we seeing here is that actually stress increases the immuno suppression the tumor micro environment and facilitates immune dysfunction via other molecules as well including pdl1 and Cox 2 it can also facilitate imp expression of molecules that are increased in survival of cancer cells like cycling D and bcl2 and bad and it can potentially promote the production of choatic molecules so that's your vef um M Matrix metal proteinases mmps um and I6 and I8 so actually working on our stress has a major physiological um benefits as well as psychological benefits within the cancer setting so assessing distress always be on lookout for depression anxiety during your review and discussions with your clients it is important and you've got to make space for these discussions but also boundaries them you know unless you have have additional training you are not a counsil psychotherapist or psychologist as an NT and you do need to find them additional support if they're really struggling um if they're red flags if someone's feeling particularly flat or low um don't be afraid to ask about Suicidal Thoughts because you might be the one person who does ask but be aware that you do need to record and Report these um so it's it's a discussion that you need to have with your client but it is important that we do assess for distress I know it might not feel a comfortable area to be in but actually it's it's important to ask because that's how we do you know we manage things like suicide prevention you might be the one person who asks poly veal theory is really to do with um the various aspects of our nervous system and you will encounter people in all um sort of settings of the the nervous system and I think it's important for you to be aware of the polyal theory and and Steven forges who's um sort of the main proponent of it so the vental vagan nervous system is kind of our sort of relaxed digest um engage with other people um having Joy being in the present being grounded being compassionate and mindful and that's really important you have a sense of connection safety and being oriented to your environment um in a calm way and then when we go into the beginnings of the fight of flight you kind of Engage The sympathetic nervous system and you might feel Panic fear anxiety or worry or you might go into the sort of the fight the more aggressive status and go rage anger iritation frustration and then some people will blow past that and go into the dorsal vagel where they actually just numb and dissociate and depressed and feel hopeless and helpless and shut down um and they can full body collapses and they might become more immobile and might have decreased heart rate and blood pressure and and sort of it's sometimes from people can be sort of a preparation fi for death as well so you might encounter people all these different states and different techniques help in different ways so when you're in the sympathetic state for example you know breath work can be really really useful when you're in the dorsal vagal free state you don't want to do things that engage the parasympathetic system any further you actually want to kind of give you give time to become deactivated more grounded and bring yourself into the dental vagal system but you don't want to further stimulate progression so I think it's important for us to be aware that sometimes actually they require different interventions so from the medical talk kit when you've got someone with psychoemotional distress what do we have um we've got anti-depressants anxiolytics or beta blockers and out of them beta blockers are probably the ones that I think have the most utility in cancer in terms of actually being beneficial in other ways and sleeve there's normally Zed drug so that's your zop zulm Etc the problem is that when you know cancer patients get prescribed these things within the cancer setting it's kind of becomes again another sticky PL are you feeling depressed here is an anti-depressant well cancer is depressing sorry but that's just the fact of it so actually what we should be doing instead of prescribing people anti-depressant going what kind of support do you need what kind of psycho emotional support do we need to give you um and then yes if someone needs to go in anti-depressants to be able to function and get to their treatment Etc fine but it needs to be not the first thing that comes out of the medical pocket really the other thing to be aware of actually is that there there might be some potential interactions between sort of cancer treatment and some of the medications that are being given out so in 2018 um there's large breast cancer cohort in the UK that showed that SSRI use was associated with a 27% increase in breast cancer mortality um and the mechanism is thought to be the interaction via cp2 D6 so the idea of it is that if you use things like peroxy tee floatin or bupropion they might inhibit C 2d6 and interfere with the activation of tamoxifen into the active drug called endoxifen but not all studies agree um and so there's also um a lean and a forward movement towards using more things like calpro and esalo um because they they interact with CP 2d6 to a much lesser extent provided there are no other contraindications there's also some concerns around serotonia receptors in ovarian cancer with reduced time to progression with SSRI use so I think it's still a developing um area really and risk benefit needs to be medically evaluated up to the most recent evidence free resources for support for clients that would have been given some by their cancer specialist nurses but it's also good to remind them where they can get support some Millan maggis cancer support UK you can ask for referrals via the clinical nurse specialist as GP for psychooncology on counseling support so it's important to be using those as needed um books um for metastatic cancer you cancer Whisperer sorry it's misspelled here um and life shocks are great by sopia Savage um mindfulness based cancer recovery it was what we discussed um as support during cancer treatment that's quite a good thing to do and cancer survivors companion remember that actually can be quite difficult to cope with feelings after cancer where all the support gets withdrawn you suddenly left kind of reading from the shock of it or kind of going hold on a second and your family and your friends might expect you to be fine well you you you you finished with the treatment so what's the problem um so it's important that we we also still look out for the impact of having you know the whole burden of of being diagnosed and treated come down on our client like a ton of bricks after they have completed treatment um integrative talk it you know self-help advice is really important something we should be considering um with with all our clients you know breath work for 78 square breathing just normal deep abdominal breathing if they can't manage the counting and it's the fastest way to shift out of the sympathetic nervous system into the parasympathetics is really useful but be aware of that actually using it with people with prop but dorsal veel shutdown can make them feel worse mindfulness so apps like you know you inside time a common head space there's lots of them around I'm sure you know all about them but be aware that it might be difficult with the trauma angle so actually if people are feeling quite disconnected and and traumatized either because of their adverse childhood experiences or um trauma related treatment they might not get on with mindfulness very well until they were able to self-regulate a bit more yoga multiple stud is showing benefit and stress and improving quality of life in patients with cancer so it's important to recommend time and nature time to connect to others the Temptation is sometimes when people are feeling sick and overwhelmed is to withdraw but it is important to to be able to connect journaling can help us process emotions since showing some benefit within the cancer setting as well EFT so emotional Freedom technique or tapping is something that um you know many Charities use the have EFT practitioner teach the technique and I've also given you a link to the combined psychology and EFT course as well and grounding exercises for anxiety and you can Google those but like 54321 to making sure you're paying attention to your surroundings um and not letting your your thoughts run away with you referrals you know you might consider referring the client to an mbsr an mbct course you might consider them exploring private psychology of counseling if there isn't enough provision elsewhere so particularly where there trauma it's a bit underserved in the NHS um it's they kind of go okay here's some CBT and CBT is a relatively blunt psychological tool don't get me wrong it's lovely for certain things however um for trauma it really isn't the right tool to use particularly at the beginning you need to have something else and things like attachment Focus EMDR can be transformative for complex PSD or complex sta so um it's important that if someone doesn't get on with one style of therapy counseling we don't automatically assume that no this is the one thing it's a little bit like not getting on with one supplement you know you can't assume the whole tool kit is not going to be appropriate um so sometimes it's worth looking out for integrative psychologists and there are psychologists who are trained in multiple different therapeutic approaches who will be able to design a completely personalized plan for the client yoga therapy is really one toone integrative Mind Body support that will cover everything from body work to mindfulness and breath work and talk about psycho emotional and spiritual well-being as well at the moment I'm looking at building a directory with the yoga organizations but there are some teachers below who both practice yoga therapy with um clients with cancer but also teach others to do so so just a few links for you so let's talk about HP access support that's something we can do within this setting as something that I certainly will address with every single client with cancer comes my way um that's used alongside all of the the psychoemotional management that I've described above because it's really important that we don't just Chuck some adaptogens and people and expect that to be the solution it it is all about support connection regulation you know parasympathetic nervous system techniques it's about the whole picture but equally hpf support can be really important in fostering people's resilience through treatment and helping them recover and helping them with cancer related fatigue so they are important tools but just making sure that you don't use them in isolation so I've outlined a few there's lots and lots of adapt I mean you can run a couple of pages of those but um panex gening is one of the most commonly studied some studies used panex quink folus which is the um American gin saying dilum um riola ashwaganda Tulsi bman and gizer might be Ed for in depleted States and alth cus inosa I'm not going to go over all of them um because I've touched on some of them before but I'm going to cover the top five adaptogens and we'll go from there the other thing you need to remember is the mushrooms that are adaptogenic of course um so cord chips and NES in particular for energy support ra is really calming so very good for anxiety um and it's Latin name is Gad dermal lucidum so um I'm going to be covering mushrooms in much more detail within the immune modulation um part of our discussions but just be aware of the fact that mushrooms do absolutely have adaptogenic effects on the um the nervous system and the HPA axis as well um and don't forg pH fle serine it's very valuable in high cortisol States particularly when you have a high nighttime cortisol might interfere with sleep so pic gen s can be uh in different forms so red is heat heat treated or it can be white which is not it contains a whole number of different components including genen aites which are troponoid zonins and these are things like rb1 RG3 Etc it also contains a whole number of other compounds and the actions of panex gening are that it's an adaptogen General stimulant in tonic nervous system stimulant anti-depressant might lower blood sugar and cholesterol has antioxidant immunomodulator effects can be hepatoprotective and uh can be a cardiac system tonic and a male tonic so let's think about studies in cancer it can be valuable and cancer related fatigue potentially there was a recent 2020 phase three trial with 438 patients with Korean red ginsing which is panagen sing 2,000 milligrams a day in coloral cancer patients alongside with f Fox 6 chemotherapy in and it showed red significantly reduced cancer related fatigue compared to placebo um in animal studies and cell studies it also appears to synergize with f Fox type um therapy there's a small 30 patient RCT and epithelial ovarian cancer where it showed there was improved emotional functioning decreased symptoms of fatigue no vomiting and reduce anxiety so but unfortunately no benefit on survival um and there are some negative trials as well but they usually use quite low doses of um panics there might be potential for broader impact we need to watch this space of course it's not up to us to say we're in any way diagnosed treat or cure cancer but I think it's important to think about some of the adjunctive treatments that might potentially be having some good impact so small stage three gastric cancer trial um by sual showed there was immun modulation during post-operative chemotherapy for these patients and there was actually a much improved 5-year disease-free survival and overall survival rate in patients taking the red ginsing powder during their postoperative chemotherapy so it's nearly double you can say the 5year disease free survival is 68.2% in those taken red red gin sing versus 33% in those are not and overall survival rate of 76.4% versus 38.5% so that's a statistically significant difference and certainly something for us to consider there's a lot of molecular potential in panic gen saying and of course we've got to remember that any studies that just look at molecular mechanism are usually cellular or animal studies and have to be interpreted with caution cell studies are largely just to peque your interest and really not particularly useful for interpreting um things properly animal studies are a bit more powerful but as we need to remember the best studies are always the human ones what we know is that ginsen contains a number of different um compounds that might have um an impact on multiple signal Pathways associated with inflammation reducing oxidative stress impacting on reducing angiogenesis and metastasis and also potentially affecting the stem cell like properties in cancer cells so for example ig3 genocide might suppress breast cancer Stell like properties and have angiogenic proposes as well so it's certainly an area to watch here and the way that RG3 does it it appears to inhibit the ACT activation of hi1 alpha which is a hypoy inducible factor and therefore stop the signaling that upregulate socks and BMI um proteins that will then result in um conferring stemlike properties so something to watch um in the with great interest over the next few years so of course as a reminder drug Hub interaction always check individually but I think something that is quite interesting is that choal in 20189 um did a study where daily administration of Korean reged ginsing at 05 to 3 gram of extract with um uh over 60% dry ginsen content didn't cause any significant herb drug interactions with drug metabolizing enes and Transporters and this was a human study so that's really important there are a number of herb drug interaction um tables and databases this particular example comes from Meda but highly recommend um registering with Med herb as a practitioner just so you can actually access their um herbal monographs and they herb drug interaction tables because yes of course you will be using the uh natural medicines database interaction Checker but I think it's quite interesting to see what's happening they update them regularly so something that's very useful gy stopen ailum is one of those um relatively unknown adaptogens but I personally love it it was um traditionally considered an immortality Hub um in guu Province um and the traditional use was in diabetes metabolic syndrome aging and neurogenerative diseases it makes nice tea you can get on nav Organics and can also be used in capsules or a tincture format the main con constituents are gypenosides which are very like the ginsenosides in ging but have slightly different properties and I tend to find that it's not quite as activating a herb as panex is they also contain steroid flavenoids and polysaccharides so the actions of gyem are that it's adaptogens cardioprotective hepatoprotective neuroprotective anti-diabetic anti-obesity anti-inflammatory and has anti-neoplastic action so neoplastic is cancer so anti-cancer actions um that's that's just molecular mechanism though so we've got to remember that and there are the number of potential benefits that has been shown to reduce anxiety in a randomized control trial of 72 healthy subjects under chronic stress it's got a huge you know huge experience in traditional use for being an adaptogen so it's something to consider and there are cell and animal studies being conducted to look at anti-cancer effects and it appears that gypenosides resist proliferation activate oxidation of ptosis and tumor cells but have the opposite effect in healthy tissue so actually it's really important that remember adaptions are normalized they're balancing they don't just have one effect in in one situation the beauty I think about herbal medicine is that it is context dependent and so it's interesting to see these studies that show that ganocy have one effect in tumor cells and a different effect in in normal cells so context is everything roia again one of my favorite herbs U main constituents is are flavonoids fenal propanoids and lots of other glycosides and terpenoids and so cidde and rosin are the main bioactive ingredients um and you will find quite a few studies on cidro side um in literature so the actions of radiola that's adaptogen tonic anti-depressant anti-inflammatory immunomodulator antic so reduces anxiety anti fatigue neurotropic and neuroprotective the important um consideration not using rodal is U bipolar depression though multiple human studies showing there's an adaptogen effect on the hbaa AIS with clinical benefits in fatigue resilience and mood and have provided you with a great review paper and actually it's worth reading not just for Rola but for the beautiful overview of chronic stress and its impact on the body in the first few pages but don't forget the check interaction to check interactions and actually rodol unfortunately inhibit cp2 C9 in humans so I can't give it to any patients with tamoxifen and um unfortunately Rola in terms of um anti-cancer effects in early cell animal research just to be aware of remember not to make any claims around that so rosol extracts and cidro side inhibit the mour so that's your PK act mour pathway that drives proliferation survival um and they might also reduce angiogenesis through D regulation of the hif1 alpha and hi 2 Alpha um um hypoxi inducible factors um also inhibits other proliferation Pathways so Jack St or mer and might activate apoptosis and oophagy appropriately in cancer so these are kind of some of the main players in the anti-cancer activity of a slide um and there's potential Synergy with a patent there's some very early data on that so it'd be interesting to see again is is there a role for some the adaptogens and synergies with conventional treatment withania Amro Wasaga has been used in ayurvedic medicine as a strengthening and rejuvenating tonic um for a number of conditions associated with fatigue weakness wasting or condoling um it's regarding AED asasa rasayana herb so that's actually a longevity tonic and a sort of a rejuvenating tonic and it's considered to increase the resistance of the body to stresses Revitalize the body in debilitated conditions and might potentially promote longevity and often called inding so a number of um main constituents in here that I haven't listed all out but you will see withaferin and withanolides being um studied extensively in literature and the actions are that it's adaptogen anti-inflammatory anti-neoplastic antistress neuroprotective cardioprotective and anti-diabetic and the potential benefits within the cancer set includes stress you managing stress and fatigue and improving quality of life in cancer and the was an open label trial in humans in 100 breast cancer patients where it was shown to improve fatigue and quality of life scores and the number of different cell animal studies I haven't highlighted all of them but there are a number of diverse components like withanolides and withaferin a that have been shown to have inhibitory properties against many cancers including breast colon prate um I'm sorry colon appear twice ovarian lung and brain Al imum suum or holy basil ulsi is another fantastic adaptogen from the ayurvedic tradition and just like um ashanda it can be used as tea of course you know par herbs as one as well as in other forms um you in terms of powders or um capsules or tinctures and the constituents include eugenol rosmarinic acid appenine number of others including lolan lolic acid and kosic acid so the actions of holy basil are that it's adaptogen antic and anti-depressant it's got antimicrobial effects which are very interesting immunomodulator hypoglycemic anti-hypertensive hypolipidemic um and radioprotective which is interesting and hepatoprotective so might be very useful to use within the treatment setting for support um there's an overview paper provided if you really want to dig in to holy basil um or Tulsi and and find out more and there's definitely potential effects on act as immun modulation although it's a lot less studied than um things like um you know panex ginsing or rodol withania uh and there are cell animal studies in terms of um Tulsi and cancer and it was shown that TOs and some of the phytochemicals of outlined have prevented chemical induced skin liver oral lung cancers in Animals by increasing antioxid activity oring gen expression and inducing apoptosis and inhibiting angiogenesis and metastasis but again remember these are all just very mechanistic studies and we need to see them in humans to show that whe that has an impact nervous system support might be useful if someone's feeling particularly anxious I'm not going to cover nerving in detail so nerving herbs are nervous system supporting herbs and some of the adaptogens are nerving as well and there are some common options below so skull calf passion flour Camal and lemon Bal and you know we can make great teas you thinking about teas don't discount herbal teas therapeutic um I do a lot of my um planning around what people are going to be drinking so I will say to people if you're going to be drinking a tea you might as well be using something it might support your your body in your nervous system and CMA is a good source of epine as well which is really good and other options of course we we got other options with line taking away from food go B complex and lots of other things that we can do to support the nervous system as well saffron is quite interesting so again saffron is um U great in terms of having some the anti-depressant effects um and something to consider too other support for anxiety um you will hear about hanoo in um the sort of cancer research circles and Magnolia the hok and magnol are both come from um Magnolia bark and there are human studies that show anxiety and mood benefits with um things like reor which is a combination of magnolian fenin and there may be some potential having anti-cancer effects so remember they cell animal not human so magnol has been shown to prevent or inhibit the growth of various cancers from different organs hoco exerts a really broad range of a number of different signaling Pathways induction of cell cycle arrest inhibition of EMT which is epithelium Miss and chyal transition which is where the cell goes from stationary to crawling uh suppression of cell migration Invasion VI downregulation of the mmps inhibition of metastasis and anti-ang antien sorry anti-angiogenic effects via decreasing bedf and VF receptor so it's something that we are use clinically from the anxiety perspective and it's great if it's got other um anti neoplastic good side effects on that so we are we've covered quite a bit around the sort of psychological emotional and spiritual support um within cancer and just remember that's I think that's a ground workor that you need to do with clients very very early on from the beginning from exploring the role of stress in when they cancer presented to actually how do how do we support you through treatment out the other end or when you're in maintenance therapy going through metastatic um treatments so really really important the reason I put it up front is because you can do whatever fancy I know biochemical pathway things or you can do all sorts of things but I think until patients feel supported grounded and and don't let fear Drive absolutely everything you're not going to get optimal results so it's really really important that we support that so the role of Cadian rhythms in cancer again it's now the kind of foundational um lifestyle medicine thing that we need to be thinking about so terms of Cadian Rhythm and cancer risk we absolutely know now from a number of different research papers the disruption of pan Rhythm plays a key role in tumor Regenesis so that's generation of cancer and facilitates the establishment of the cancer Hallmarks and actually then it also becomes a bit of a vicious cycle Because the actual process of cancer the oncogenic process then also weakens the Cagan Rhythm and all you go around found in a in a vicious cycle and there are several lines of genetic evidence from studies that connect the disruption of Cadian machine machinary to lymphoma HPA acelia carcinoma lung cancer and different humor types and there's also very interestingly a connection between um Cadian um Rhythm and cancer metabolism and there's some very very interesting early um thoughts around whether we should be timing our chemotherapies in a different way to maximize the Cadian Rhythm effects um we also know the disruption of Cadian Cycles by light at night exposures or chronic exposur stress related mediators have been linked to an increased risk of breast cancer and epidemiological studies uh one of the many reasons I don't do shift work anymore um disruption of Cagan rhms can also accelerate humor progression so it is essential ultimately that we talk to our clients about biorhythms and and Cadian rhythms and and how to support that balance within their life sleep disturbances in cancer of course are R so it's important that we we might have had sleep disturbances before the cancer diagnosis related to shift work or maybe sleep deprivation and stress and then we when we get to the cancer process there also other lot of sleep disturbances and it might be related to physical or psychological effects of cancer like anxiety depression or pain or might be related to treatments so hot flushes when women on hormonal treatments or steroid related sleeve disruption which is huge I mean and I have to have a number of discussions as a a doctor with with oncology teams about sort of trying to um reduce steroid doses um when people don't have any effects after the first dose of specific chemotherapy to try and get them some more sleep because and some people it really sends them off um into a bit of a tail spin and can also even cause at high enough doses can cause really significant psychiatric effects like psychosis so in terms of what do we do to promote healthy Cagan rhythms it's a really really simple and quick summary but I think it will help um you make your handouts and help you start the conversation with your clients so don't forget morning light exposure it's really important that you know wake up and get proper light exposure on artificial light getting Outdoors every day as much as possible physical exercise and meal timings are important so not eating late at night because you're going to be disrupting your normal Rhythm removing disruptions like blue light exposure at night using things like blue light blocking glasses making sure that um you know computers and devices have night shift or blue light filters engaged winding down the nervous system in the evening is really important you we we it's I find it quite interesting in that we spend so much time trying to wind the children's nervous system down before bed and we have the whole bedtime routine but we expect adults to just lie down and go to sleep and sometimes adults can but actually when they're under a lot of stress they really can't and they need to be able to wind their nervous system down so trying to opt for relaxing and non-stimulating activities in the you know one two hours before bedtime Yoga Nidra can be a really powerful pre sleep relaxation towards an inside time and the multiple different tracks around you tube you can assist sleep as needed with nutrition supplement interventions if things are you know really getting out of control you might consider referring to GB for melatonin they use things like Cadian or similar um brands for sleep disturbance as a gentle alternative to zed drugs and please don't ever refer to GPS for melatonin for any kind of cancer support because it's not licensed for it it is licensed for sleeve disturbance so it's important that we use it for the um um the indication that the NHS can can provide it to us on and if you need more information make sure that you read the Cadian code book or listen to Dr sain Panda's podcast with Dr chaty and it's it was a great discussion so I think you or potentially your clients might enjoy that lots and lots of references for you to go through if you would like um and a few papers uploaded as well where the list of what's essential and what's optional I hope you find it really useful ________________ 3.4 Microbiomes, GI function and cancer hello and welcome to our lecture on microbiomes and cancer it's just a quick reminder about the systems approach um and that we've covered mental emotion spiritual health and biorhythms in the previous set of lectures and we're now going to be moving on to healthy microbi balance and GI function so let's talk about microbiomes and cancer so which microbiomes any microbiomes is pretty much the answer um we particularly going to be focusing on the GI microbiome that involves oral microbiome stomach small intestine large intestine um anywhere within the GI tract that's relevant for us um we will also talk about the vagina microbiome a bit um and there are plenty of other microbiomes that we would need to consider in specific disorders but actually there is no commercial testing available so w be covering uh things like the skin microbiome and urinary tract and lung microbiome in this lecture in any great detail because there is no commercial testing available so microbiomes in cancer RIS you know the microbiome's been discovered to be involved in the initiation and progression of various types of cancer so there some very wellestablished links that we know of already like helicobactor pylori and gastric cancer gisis and bladder cancer and there are plenty of other known links as well like fuser bacterium nucleatum and colorl cancer and potentially oral cancer as well there there's emerging evidence around many different microbiome sites um for example estrobolome and breast cancer where we know that the microbial composition of the GI tract can affect the extent to which estrogens can get deconjugated and recirculated via the anhepatic recirculation system um and therefore might impact risk of estrogen-driven disorders and there are many many other things you might consider so research the relevant type and if you're going to be interested in specific canc in how a microbiome of that environment might affect it then uh go to bobm and have a good search around the research is moving very very fast you know the the same lecture given next year is is going to look the same because um we are finding out more and more and um there literally hundreds um thousands of papers being published every month so let's think a little bit about the GI microbiome and actually how it's related to the different cancer Hallmarks for example and this might be particularly relevant to GI cancers but also has some systemic effects so I have included this paper within your reading but I'm going to highlight a few things around it and that's number one that actually a number of different hallm marks are being affected by the intestinal microbiota um and one some of the specific bacteria that might be involved are fuser bacterium nucleatum uh which makes a toxin called fade for example in fap 2 um but also um specific entot oxygenic be fragiles um which is in blue here and that makes bft which is um bacteroid fragilis toxin and what's really interesting about it is that toxins from some bacteria like bft or fada from fuser bacterium nucleatum can actually affect um proliferative signaling in in colog cells so for example they affect the way that eerin um signaling and tobine is affected and therefore activation of pro-oncogenic Mick and that dries proliferation in colon cancer so it's an important one for us to think about actually some of the bacterial toxins can drive this proliferative signaling as well as driving inflammation and what's also interesting is because there's a Counterpoint to all of this that um we can our gut microbiome can also make beneficial compounds like butrit that will actually help us with our cellular energetics um and might also help us um sort of lift the micro the um immune inhibition within the can cancer environment so it's really important that we think about the balance of different bacteria some of them are going to be harmful um in the wrong setting like the inot oxygenic be fragilis or Fus nucleatum um and that will basically Drive um cell proliferation tumor promoting inflammation some might generate enough oxidative stress to actually promote genomic instability in local um vicinity so local coloral um cells um and some of them will be protective so buid producers are going to be protective through um maybe regulating cellular energetics and colorl um lining cells um and they will also be influencing the immune environment which we'll talk about a little bit more in the next lecture so have a read of this review it's a really great review and I think you you'll enjoy that so let's talk a little bit about um very much in brief about microbiome life cycle ereal cancer I will go into it a lot more in one of the advanced practice modules on on coloral cancer but this is really great overview paper which you will also have access to that talks about the influence of diet and lifestyle on the um alut microbiome and how it might also influence choral cancer risk so for example here they talk about how um for example obesity uh is associated with increased LPS load in the gut and that can promote tumor promoting inflammation which is um obviously um detrimental within this setting and also that obesity and physical activity have opposing effects on aaman mifa um levels so the Obesity decreases it and physical activity increases it and we know that aiman is absolutely essential for maintaining the muin lay and having good gut barrier function um as well as um then interacting with the T-Rex cells and inhibiting uh tumor promoting inflammation within the mucosa layer so keeping a healthier I canania by maintaining healthy weight good physical activity things like aonia and pomegranate for example and and fasting as well can can all be beneficial within the setting the other things we know is that obviously D could contain adequate levels of dietary fiber and ideally we want to get most of it from vegetables not over relying on grains which most people do as well as physical activity can promote elevated levels um of short chain fatty acid producing bacteria which is great because we know that number of short chain Fates particularly um things like butd will have a fabulous effect in maintaining um colonos site um lining really and also can uh talk to the t- egg cells and induce uh t- egg cells to decrease inflammation and there's of course other not so beneficial interactions within this so uh excessive amounts of um red or processed meat can promote the growth of hydrogen sulfate producing bacteria like bopa for example do so for vibrio and also can um cause variations in theary metabolism that can affect the gut barrier function can also um induce even induced DNA damage in in colono sides and there are specific material products we might want to think about if if the gut microbiome is such that it produces a lot of TMA that gets converted to tmao then that will be linked to metabolic disturbances um and can also link into the uh bacin metabolism so I think there's some clear guidelines around where we can think about you know um weight maintenance physical activity um getting a whole wide variety of um your vegetables and low sugar fruit um plenty of fiber with in our diet and avoiding processed meat and decreasing red meat and and sort of um animal dve saturated fat to avoid having this um not so beneficial effect in the G microbiome and again um have a read through the review on this one um I think you again it will be useful for you to have the overview of the evidence in more detail so microbiome cancer therapies not only does the microbiome balance affect whether we are at higher risk of of getting specific cancer types you will also affect um us when we go through cancer therapy so for example probiotics may be helpful in eleviating therapy side effects as we've seen in months too and we know the microbiome has a pivotal role imuno modulation again we talked about the relevance of it an immunotherapy and support for that and of course we also need to remember that during treatment the microbiome gets knocked around such a lot and we need to support recovery after treatment is complete so that's just a quick reminder of um going back to have a little review about immunotherapy and what we can do to support that and the fact is actually we need to lead with food first so what are the risk factors for disbiosis I know that you as professionals would know those anyway but just a quick little Gallop through it's important that we have a good microbiome setup from birth really so again avoiding C-sections unnecessarily um breastfeeding as much as possible childhood environment that includes you know good dirt and potentially exposure to animals and um and a wide variety of various microorganisms uh nutrition obviously plays a massive role um so as we know nutritionally devoid diets and standard American Standard British diets not going to have a favorable effect on your gut microbiome physical activity is going to impact your God microbiome directly and regardless of nutrition which is fascinating stress is going to impact your G microbiome as well um other cidi so obesity but there's a chicken and egg situation here so actually what came first we're not always entirely sure medications as we know has a have a Major Impact that's antibiotic antifungals PPI steroids and a number of other things that might impact um um our gut microbiome and environmental exposures chemicals toxins or pesticides for example and infections of course so getting a gastroenteritis something along those lines and many more but this this is just a kind of when we're questioning someone for how relevant this particular aspect is going to be to them not only is it relevant to their particular cancer type and cancer therapy but also looking at their history you can see just how much G biosis might play into their overall systems assessment so thinking about assessing the microbiomes in a client with a cancer diagnos says what would you do and the key considerations are what to test will very much depend on cancer and therapy type so for example choral cancer we know that store testing is going to be very very important you know head and neck cancers you might want to actually have a look at the oral microbiome once someone's completed therapy and see what you can do um again with um certainly with with pelvic cancers there may be some relevance um for women in testing the vagina microbiome as well the key consideration well will depend on when to test okay so after chemotherapy and radiotherapy I have to say I usually allow 3 to four weeks minimum for the for the things to settle after treatment and then test to see where we're at with the G microbiome and how to modulate it from there to support recovery and before immunotherapy I think is an important test to do to see if there's anything you can do from the dietary perspective to try and support healthy can M and the bacteria levels for example until we know bit more about what what we can give within that particular setting so um there's not much point in obviously testing it during active treatment like chemotherapy and radiotherapy because actually is going to be changing anyway quite rapidly and it's not going to be as relevant within that setting so you have to be quite level with timing these things um as well so all our vagina microbiome see we've got uh inv Vio clinical has excellent uh option for vaginal ecologics and oral ecologics or you can combine all three within a complete ecologics B and I think that's that's a wonderful and unique service that they offer which is great so oral microbiome and oral health really um we know that there specific um bacterial species particularly the ones that associated with gingivitis like poonis or fuser bacterium nucleatum that's also associated with choral cancer risk they can induce the production of inflammatory cyto kindes and and cell proliferation and inhibit cell death apoptosis promoting also Invasion and migration um through actually interacting with our genetics and also interacting with the micro environment anyway it's an active area of research so we need to watch this space because um the relationships are still being established so what you might do is if you did an oral um ecologics is to have a look whether if there is a significant load of particularly um Troublesome bacteria and red really like the red complex and and fuser bacterium then you might consider things like some The herbal mouthwashes for the remove phase um ensure Woods liary flow in replace that's really really important um repair with things like Zin carine or licorice swis around the mouth and you can just get licorice extract um to do to do that and then consider appropriate oral probiotics for inoculate where it's indicated by testing and really you're going to be tailoring all of this and not going to give you a protocol it's more about things to consider within your toolkit and don't forget other aspects of oral hygiene it's important to avoid toothpaste with asels and plenty of the other nasties because there's quite a lot of um sort of antimicrobial compound use within commercial toothpaste that it's best to avoid need to consider root canals and persistent dental problems as inflammation sources as well it's going to be relevant for our next lecture but do consider that and an amalgams is sources of mercury which is is relevant for from the detoxification perspective it's really important that there are no Dental intervention until unless absolutely necessary during active cancer treatment as much as possible because it kicks up a lot of inflammation H and this is the last thing you want to be doing during active treatment and it can also cause active bacteremia it's very well documented after dental treatment the number of bacteria circulating around in your bloodstream and you certainly do not want this in a um imuno compromised population so um ideally I would usually say unless it's absolutely necessary I would advise against Dental intervention during active um chemotherapy for example consider reviews with biological holistic dentists they're really the expert in the area so something to consider and then uh usually if um your clients are being given bis phosphinates they must have a dental review because if they're given bis phosphinates um like alendronate or zolendronic acid something along those lines um they do carry a risk of osteonecrosis of the jaw which is a really significant complication um even if it is rare and so before starting that therapy it's best that they get reviewed by the dentist and avoid any dental treatment um uh during during the disys phosphate therapy um which is important well in terms of rgi microbiome assessment I know from point of view of the stomach and looking at sort of of gastric cancer and also um um yeah gastritis I guess is is a non-cancer setting is H pylori of course St antigen testing is something we're familiar with um and we know that it's available via a number of different store tests in medicine um we also would use Rapid testing um during upper gii endoscopy to find out if you you're going to put a scope down someone it' be good to find out quickly whether they've got an active hpor infection um small intestin there's indirect assessment for CBO small Ines bacterial overgrowth via breath testing so glucose is used in most cases La chus if there's any suspicion of distal small intestinal issues fractus is an up and coming test but um it's not really widely accepted by the conventional settings so I think we still need to do some work and some research around that it's not in the guidelines so that's something to be thinking about direct assessment um of the small intestin gut microbiome is only really used in research settings or large teaching hospitals um so that's would be a small microbiome aspiration during OGD which is is suffa gastro duodenoscopy um so for us I mean I tend to use in Vio and AA Diagnostics via those guys to do my my breast testing and we are waiting for trios Smart in the UK it's a new um three gas test which will assess hydrogen methane and hydrogen sulfide it's available in the US now and we're waiting for it to come to the UK and that will be very very interesting if it does come I mean it's still very early in terms of hydrogen sulfide breast testing um research but I think it'll be it'll be a fascinating tool to trial St testing options so the key considerations that compliance and cost they are they are very very expensive I know people are using um some of the Consumer Directed tests like you know um Atlas but I always think that really they don't have enough information um for us as clinicians to be able to act on it properly um and we also need to choose our St test depending on how heavily pre-treated the client is if they're really heavily pre-treated we'd want to know the actual sensitivities um to treatment in the particular um organism who might be trying to Target so um at that point actually we might want to do a stool test that has a culture component so the options for store testing include PCR only and that's polymerase Chain Reaction that's just looking in the genetic material that you can identify in the store or PCI in culture and that means that you're looking at the genetic material the various bacteria Fung Etc but also you're going to be culturing um these um bacteria or funan looking at whether they're going to be sensitive to specific treatments um and quite often they both of these tests also include microscopy actually looking at the stoland micros scope and seeing if there are any interesting things swimming around like protol parasites so there's limitations um to PCR only tests as much as um this has kind of been touted as the next big thing I think that it is great however you don't really get any sensitivity so you have no idea whether what you're going to be using is going to be inhibitory um to a specific disbiosis you're trying to Target um and also the other limitation is there is something called PCI interference um that will be a proportion so where the the stest might come out as negative when actually there is um say a protool parasite in there um because of interference with the actual technology which is why in most cases not in all cases but in most cases I would do a BCR and a culture test in in my clients and the thing about G up um I have to say if I am going to be using a PCR only test I will use inv Vio um because I think we should be supporting our um British lab that's CQC registered and I think the Humphrey and the team are doing amazing work um the other thing about GI map I mean the whole antibiotic resistance component is utterly useless because we don't actually know which bits of antibiotic resistance Gene saying which bacteria it's like looking at a soup and trying to pick out a single carrot it doesn't really it doesn't really work like that so um I'm not a huge fan of of of giab for that reason I find it PG ecologics a better test really if you're going to go for PCR only and if you're looking at PCR and culture then there's um two really good options doctor's data GI 360 and goova gifx comprehensive test um and obviously um both of these will have step down um smaller test to do if you're going to be reviewing someone's gut microbiome because you you really want to be retesting with a minimal amount of investment so you want to make sure you've got a smaller St test to go back to at some point so and again what you use will depend on what you what you like what you get on with what you find useful in practice and what you find most supportive in terms of um uh being given with support with interpreting results and actioning those so the management of G microbiome I could spend 6 months just doing that probably more uh so there too much to cover here but just remember your 5r protocol so of course remove replace repair reinoculate and rebalance uh and I will pop up the um ifm handout on that that you mostly aware of anyway and there will be specific adaptations in different cases um for you for example when you do have small intestin bacterial overgrowth it is essential to use prokinetics as a part of this 5r program so um do make sure that you use something appropriate for whatever disbiosis you've got and to be dealing with at the time um other things you might want to consider so again when we're thinking about Colonoscopy prep and um it's highly disruptive to the gut microbiome and ideally we would want to try and use the cleanest agents possible particularly in our patients who may have had U clients who have had cancer so this is the protocol that we use it synthesis it's derived from a couple of different people um Dr Winters has one based on a different magnesium product but I've also um seen other protocols from other um GI practitioners so this is the one that we use and we use colosan plain colaan for that um so it may be worth a trial with some of your clients if they're prepping for colonoscopy and they might not want to um take some of the more um sort of some of the more chemical Laden prep out there vagina microbiome and cancer again this is just a very very quick look and we would be going into more detail in an advanced practice module but we do know the genital disbiosis and and potentially some specific bacteria might have an active role in development progression and metastasis of gyenes and that includes cervical and demetrial avarian Cancers and there are a number of different mechanisms have been proposed um through both direct mechanism terms of um actually affecting um you inflammation within the local area or having u a promoting effect on um sort of hyperplasia and proliferation of the different cells and also indirect mechanism like we talked about the modulation of estrogen metabolism and we also know that microbiota uh composition can influence the efficacy and toxic effects of the different therapies and the quality of life after treatment and of course as we talked about before in module two is that many pelvic cancers will receive radiotherapy as part of their treatment and um can get some significant um side effects from it and we've seen studies that showed a number number of studies that showed a decrease in abundance and diversity of the intestinal bacterial species after that so we need to then try and rebuild a healthier microbiome within that area both you know vaginal microbiome and um choral um so um lower intestinal microbiome in that particular area so another thing to think about is that there are a number of things within the microbiome that includes you know viruses and specific pathogens as well as Al censal bacteria that might infuence things like ovarian um cancer development so we know about HPV relationship with with the cervical cancer and we know that that's um that's particularly specific types and that's 16 18 and 31 are particularly linked to increased risk of cervical cancer but we also um need to consider the other infections that's pathogens like clamidia and pelvic inflammatory disease that's been also related to um aarian cancer and and it's partially thought that's because they they um generate such a big inflammatory response and we know that inflammation within is important um in terms of um promoting um cancer and also promoting its progression um so what do we do about the vagina microbiome if if we tested and found it to be um having some kind of imbalance so it's important to restore and support the dominant like the Basil's population um because that's really what the vagina microbiome is designed to have and you might use probiotics or suppositories so there's three options here that I use quite a bit and they are different strains so it will very much depend on what kind of results I'll get in the vagina microbiome test in terms of what I use um support HPV clearance is necessary that's really important you know it's important from of course the sin so cervical intraepithelial neoplasia so that's your little um sort of discos of normalities you will get on smears but um also of the cervical cancer but also we are now thinking that HPV has a kind of a wider inflammatory um action on on various um sort of various reproductive cancers in women so it's important that we support clearance so there are studies out on various um herbal support and um probiotics Etc not all of them agree so the suggestions below are based on kind of limited evidence and my understanding of the pathopysiology of what HPV does and my clinical experience so it always start with General immune support because of course you know we are relying on the immune system to clear the HPV and that's you know usually ACD in in zinc and you might want to consider vaginal probiotic and some of these have been linked to significantly increased a risk of sorry in increased um chances of you clearing HPV um various leab bacillus preparations have been used um and with different strains uh consider mushrooms so turkey tail and RI have um limited specific data in vaginal HPV but there has been a study that showed after two months of therapy that's um with these mushrooms there was an 88% clearance of oral HPV 16 and 18 versus 5% natural clearance that's a really really significant effect and in terms of harm when know that's a very very low risk of harm so I I always think that's worth a trial uh consider green tea there is a topic of preparation that we use in different type of HPV which is related to gentle warts and we might be a bit unclear about oral dosing for it but there's low risk of harm so if if someone is open to drinking green tea or maybe taking some supplemental green tea as a part of a maybe a microbiome restoration formula that might be useful and we know that TCM also shows efficacy um other considerations for vaginal Health would include having good feminine hygiene so no douching no commercial fragrance products water only um in terms of washing down there cotton underwear and watching tide clothing um making sure we've got good sanitary product choices um so using menstrual cups organic tampons and sanitary towels and avoiding commercial um products that are laid in with chemicals and of course STD protection as well and just as a quick wrap up I think it's important for us to just highlight the importance of supporting healthy GI function beyond the microbiome in cancer and we know that malnutrition might be common in specific cancer types and upper GI and head and neck Cancers and it's often really poorly managed with high calorie high sugar drinks that that get poor down people and some clients that have had a neck cancer or API cancer might have a peg feed so might have actually achieved fit per 10 if the cancer doesn't affect the rgi tract we often find that the therapy does so even if it's a completely different cancer type that's not related to the GI tract at all so surgery chemotherapy uh pelvic abdominal radiotherapy steroids painkillers antibiotics all of this stuff will affect the GI tract and with surgery if there is GI surgery or actually surgery for some of the um other cancers within the abdominal C cavity and pelvic cavity um we know that there it can generate adhesions that might be disposed to um problems with the gut that might have recurrent partial intestinal obstruction or if they're higher up in the abdomen might be disposed to sio because of um impaired motility and impaired um sort of normal function of the small intestine and there's of course also considerations of where the the key GI tract anatomical components reected so for example if you reected the terminal iium and is gone your ability to absorb B12 for example your B acid effectively is going to be significantly compromised because you just don't have that anatomical part there and therefore significant consideration need to be given to making sure these are replaced um in sublingual forms for example and um also managing kind of bile acid malabsorption in other ways chemotherapy and radiotherapy will now affect intestin formability and gut mome we know that steroids and nayes can be linked to upper GI ulceration and increased intestin pability and opiates and some anti-emetics like indan Atron can give people constipation and of course antibiotic and the and antifungals and the massive impact on the gut microbiome so um it's really really important for us to keep these things in mind um and so healthy GI functions also completely um necessary for us to think about as a Cornerstone of our client's Health as we know so the digin model has been created by ifm and I quite like it and so I use it in practice to remember all the different components that we might need to address and so we need to ensure a healthy GI function to support proper nutrient status and immunological status in your clients and you're looking to optimize digestive functions that's salival production stomach acid pancreatic enzyme billary secretion that's when you to watch the ppis and a meour Etc that get given to to clients um and you would do that with supporting the um calic phase of digestion so actually getting people to look smell and sit down to enjoy their food good chewing practices avoiding consuming large amounts of water with their meals uh using digestive enzymes uh plus minus Bain if it's really appropriate it's really important that we don't just hand out um betan hydrochlorate to clients um with cancer who might have compromised um gastric barriers H and Bitters with or without Ginger are also something that you might use to light up really the whole upper GI tract um it's very very useful for that and sometimes bits can be a good um appetite stimulant for some people intestinal barrier function you need to also watch the impact of N and steroids in this case and tools you might want to use are things legine carnosine DGL or full licorice if it's appropriate soothing mucil isn't this you typical you know slippery Elms and marshmallow Etc but don't use it in overgrowth if you're suspecting overgrowth uh ensure good omega-3 and vitamin A status it's and that is again really really essential for for barrier function G microbiome we need to obviously make sure we've got adequate fiber polyphenols and then use prebiotics or probiotics as appropriate and watch the impact of antibiotics chemotherapy and ppis on the gut immunological function we need to be supporting um our short chain fatty acid producing bacteria it's really important we need to have healthy beate levels in particular but other short fatty acids will also play a role um need to support good microbial balance and support healthy secretory IG and and for that we know that um sisis Bard has um a good effect um as appropriate to the stage of someone's treatment enteric nervous system is essential to work on and that you might use breath work yoga G director hypnotherapy with things like the nerve app and it's really important to think about dig in and think about all the different components of the GI tract um support all together because it's important that we don't just focus on G bacteria that's nice but actually we need to think much wider and um make sure we think of the whole complexity of the GI track as a neurog gastro immune complex fantastic some ref refences for you and I hope you enjoy the papers that I'll upload as well thank you ________________ 3.5 Immune Function in Cancer cancer. Today we're going to be talking about immune function in cancer. And of course that's our third note that we talked about so far. So we started off with mental, emotional, spiritual health and biorhythms, then went on to talk about healthy microbiome balance and that's different microbiomes around the body and GI function and now we're coming on to balanced immune function. And of course immune function comes up in two different hallmarks of cancer and that's avoiding immune destruction and also tumour promoting inflammation. So it's really important because by working with this particular aspect we can be impacting two hallmarks of cancer. So what do we aim to do within this particular system? We may aim to decrease inflammation oxidative stress. and also support immune surveillance in a balance-specific anti-tumour response. And there's a significant role for TME or tumour microenvironment within that. And just to quickly remind you, a healthy immune system is meant to be detective, which means it should be able to detect any threat from within or outside the body. It should be internally regulated, so you should be able to regulate your immune response and be able to switch it off when you need to. And it should be restorative. and tolerant. So the idea of it is that we're meant to be able to restore balance to our immune system and tolerate things that are meant to be tolerated like self and innocuous antigens. So inflammation plays a huge role in all stages of cancer including initiation progression. Infection inflammation actually account for about 25% of cancer-causing factors globally and As we've spoken about a number of times before, there are well-known infection lengths like schistosomiasis and bladder cancer, helicobacter and gastric cancer, HPV, high-risk types and cervical cancer, EBV and nasopharyngeal carcinoma, and plenty of others. We also can see that there are pro-inflammatory factors from the environmental perspective that also play a role in cancer, and that's asbestos and air pollution and inflammatory diseases. So there's been well-established links between... diseases that drive chronic inflammation within an organ and cancer in the same organ. So for example there is a link between increased risk of colorectal cancer and a history of inflammatory bowel disease. Barrett's oesophagus is a pre-malignant stage for esophageal garden carcinoma and that's generated an inflammatory change in cell type in response to reflux, chronic gastric reflux. And also chronic hepatitis driven by HPV and M. HCV viruses and hepatitis viruses and HCC which is liver cancer. And there is a concept around that cancer is almost like a wound that never heals it's sort of this chronic inflammatory response it just keeps going without being turned off without achieving proper resolution proper control. So in terms of how inflammation might contribute to cancer initiation promotion we know that inflammation will generate oxidative stress and Reactive oxygen and nitrogen species damage DNA but also damage other macromolecules such as proteins or lipids, and that's like lipid peroxidation for example, and it results in their dysfunction. So one interesting thing to note is if you damage transferrin in an oxidative environment, it actually releases iron ions that then generate additional reactive oxygen species and then upregulate inflammation even further. So it's almost like a positive feed-forward loop. And epigenetics also plays a role, and that's sort of underappreciated, I think, in terms of having an indirect effect. So, for example, when we have high levels of pro-inflammatory cytokines such as IL-6, it can actually have an impact on the methylation. And I'll just cover this here quickly. So in a normal microenvironment, we have good antioxidant systems in place. We have raw scavengers. We have our normal internal antioxidant molecules. And. Our detoxification systems are working really well in terms of glutathione pathways etc. and we have a good balance between pro-oxidants and antioxidants, in which case we get normal gene expression and normal balance of methylation of genome. What happens in the inflammatory microenvironment is that inflammatory cells can secrete pro-inflammatory cytokines, for example interleukin-6, and that leads to activation of DNMT1 which is a methyl transferase. what happens is that it can then promote methylation in the promoter regions for specific genes that can shut down their gene expression. So you get hypermethylation in promoters for genes. tumour suppressor genes and global DNA hypomethylation. So there's an imbalance that then results in us turning off our tumour suppressor genes and decreasing microRNA expression for those that control oncogenes and therefore their activity can get increased and we can get a result in development of cancer. So it's important for us to think about Inflammation oxidative stress resulting from that as being drivers not only of direct damage to DNA, lipids and proteins, but also having an impact on the methylation of the genome. So key molecules, I'm going to only cover a few, there's lots and lots of molecules involved in inflammation and oxidative stress pathways, but particular ones that we like to talk about in terms of inflammation and cancer. cytokines, particularly IL-6, but IL-1 and TNF-alpha are also involved, COX-2 and downstream eicosanoids. And of course, the counterpoint to some of those prostaglandins and other more pro-inflammatory eicosanoids are things like resolution mediators, such as resolvins and moressins from omega-3. NF-kappa-B is, of course, one of the master regulators, and that's connected to NLRP3 inflammasome, which is a basically a factory for producing some of those pro-inflammatory cytokines. And there's a crosstalk between NF-kappa B and Nrf2, which is kind of the counter-regulator to that. And STAT3 is another important regulator. So when we're thinking about key molecules that you might want to read about in scientific papers that link inflammation and cancer, we need to think about IL-6, NF-kappa B and STAT3 in particular. So just as a reminder for NF-kappa B, we know that it's an inducible restriction factor that gets upregulated during times of increased inflammation oxidative stress and it in itself will then drive more inflammation effectively. It will upregulate production cytokines, chemokines and adhesion molecules and also has an impact on regulating cell cycle and reducing the propensity for the cells to go into operation. so producing anti-apoptotic factors, and can also produce various chemokines and cytokines that can result in upregulation of angiogenesis. So it's a significant driver in terms of the cancer and human microenvironment, really. In terms of inflammation and cancer progression, so we talked a little bit about initiation and how that might occur, but the other things we need to think about is actually how the how does it affect cancer progression and metastasis and invasion and the processes by which cancer spreads through the body. So cytokines actually activate the necessary pathways required by cancer stem cells to progress through EMT which is epithelial mesenchymal transition. That means you go from a static cell which is sitting there connected to your neighbours to a crawling cell that would like to escape and go off around the body. So it's important that cytokines secreted by those tumour-associated immune cells can actually promote that transition. And deregulation of COX-2 and PGE2 signalling pathways is associated with many tumours, particularly in colorectal cancer. And it's related, the upregulation of COX-2 and PGE2 production is related to metastasis and poor prognosis in patients with colorectal cancer. And also chemotherapy resistance. So it has a major impact on how the cancer progresses, but also whether we're going to be able to target it with therapy appropriately. The STAT3 signal, which we'll talk about in a minute in detail, is a major pathway for cancer inflammation because there's a very frequent activation of it in malignant cells, and it plays a key role in regulating many genes crucial for the inflammation in the tumor microenvironment. And we talked about IL-6 and the potential link to changing the methylation of the genome, but also it can promote haemogenesis by regulating all the different hallmarks of cancer. And signaling pathways that include apoptosis, cell survival and proliferation, angiogenesis, invasiveness and metastasis. So having good inflammation control is essential for us in terms of supporting patients with cancer. So STAT3, there's basically different STATs of different kinds, they all have a number and they have different function depending on that number. So STAT3 and to a less extent STAT5 are effectively pro-carcinogenic. They increase proliferation, survival, angiogenesis and metastasis in cancer and also inhibit anti-tumour immunity. The counterpoint to STAT3 and STAT5 is STAT1 and actually drives anti-tumor immune response. So it's a count regulator. So it means that we would want to be targeting quite specific stats to try and tip the balance to convert tumour-promoting inflammation to specific anti-tumour immune response. And the thing about STAT3 is that STAT3 is a bit of a master regulator which means that once it's activated to a significant degree, it will promote secretion of various signalling molecules including cytokines and growth receptors. that will then also activate STAT3. So you're getting this positive feedforward loop effectively. And the signaling that we're going to be discussing is that relevant to inflammation is IL-6, JAK, STAT3 signaling. So I'll talk you through the signaling pathway. But the other thing to be aware of is the other environmental inflammatory factors that will activate STAT3, such as, you know, excessive exposure to sunlight, specific pathogens or chemical carcinogens. which will also plug into that pathway. And STAT3 interacts with NF-kappa B, so again you've got that double whammy of inflammation and it's also in itself activated by things that are NF-kappa B regulated. So NF-kappa B can promote secretion of IL-6 and IL-6 in itself then will promote activation of STAT3. So it's quite a sort of close-knit inflammatory family. So if you think about this STAT3 pathway, so at the very top you can see IL-6 binds to its receptor, it dimerizes, which means it forms a little couple, a little pair, activates JAK, and that's Janus kinase, and JAK then goes off and talks to STAT3, puts a little phosphate on it called phosphorylation. STAT3 goes and finds another partner. So again, the STAT3s travel in pairs into the nucleus and then activate transcription of a number of different genes. including things that regulate the cell cycle and proliferation such as cyclin D and MYC and things that regulate apoptosis such as BCL2 and BACs and there's there are many things that it will be up regulating within that setting. So the other thing we've briefly touched on already is inflammation treatment resistance so not only does inflammation play a role in initiation promotion and progression of cancer it also impacts how resistant the cancer might be to treatment. So high levels of IL-6 actually protect cancer cells from the therapy-induced DNA damage and apoptosis by facilitating basically a counter signaling pathway. The other things to say is that actually the chronic inflammation in the tumor microenvironment has this persistent role in driving the survival and proliferation, keep going with angiogenesis and also immunosuppressing. the specific anti-tumor response within that environment. And let's not forget actually many therapies that we use in the cancer setting such as chemo and radiotherapy are pro-inflammatory as well so you can see how you can get stuck in a bit of a treatment resistance cycle. So in tumor microenvironment there's basically two things we look at. We would like to have part A, the tumor killing immune microenvironment. So we want to have good active NK cells, we want to have M1 macrophages, and we want to have a really robust CD8 response and a more Th1 driven response. And then we can actually get tumour control and tumour killing. The problem comes when the tumour becomes very clever and actually starts secreting all sorts of factors that will convert its tumour environment into more of a Th2 polarisation and actually starts being immunosuppressive and co-opting. all of these different cells around it to actually participate in its spread and metastasis. So in the immune suppressive microenvironment, you find MDSCs, and that's myeloid derived stem cells. They're the ones that can produce lots of angiogenic factors in response to the tumor talking to them. You get M2 macrophages rather than M1 macrophages, and they're more immunosuppressive, in fact. And you've got NK cells that are being suppressed by TGF beta. as one of the regulatory cytokines. So you find that actually what the tumor tries to do is instead of trying to promote the killing response, obviously it tries to hide and immunosuppress the tumor microenvironment and actually get it almost converted to its own cause and get it to promote different processes such as angiogenesis. So we want to try and repolarize it back to the tumor killing microenvironment. That's the goal. So... When do we assess the importance of immune system support in cancer? Pretty much always relevant to consider because it's going to be playing a role in a number of our patients. And the key clients, cancer, key aspects of the cancer. Cancer history, really, that we need to have a look at are recurrent infections. So if you have someone who just keeps having recurrent infections, particularly in the preceding sort of two to three years before getting cancer diagnosis, they just might tell you, I was just constantly ill. I was just every winter, I just picked up every cold going. Or doesn't ever get even a minor cold because it is normal to get an occasional mild cold. It's not normal to be completely laid out with it. but it's certainly normal to get an occasional immune response. Past medical history of autoimmune disease is very important because how we choose our intervention will very much depend on whether someone has a history of autoimmunity and it's important in the overall setting because actually it's very tricky balance because when we're trying to Immunomodulate, we need to keep that balance between not aggravating the immune system enough that it actually flares up the autoimmune disease. So combination of cancer and autoimmunity is a tricky one to strike the balance with. Vitamin D deficiency or unknown status for vitamin D is another thing to ask about. Gut immune axis, very important as we know already from the previous lecture. Antibiotics, other microbiome disrupting factors that you've learned about in... in our previous talk. And current treatment plan aspects will play a major role in you trying to figure out what you need to do to support this person. That's chemotherapy, radiotherapy or immunotherapy, for example. So in terms of tests, what do we do to assess inflammation immune balance? So in terms of assessing inflammation, Dr. Neysha likes to use her trifecta, which is CRP, SI and LDH. And total LDH you can get on the NHS, but it is harder to get. and it needs to be in the lab within eight hours so it needs to be a proper blood draw ideally. So ideally we would like to have LDH with isoenzymes and isoenzymes are basically different types of LDH that live in different tissues and can tell you something different in terms of are they associated with a malignant process or actually is it the LDH more relevant for other tissues that are nothing to do with malignancy for example. I tend to use either CRP or highly sensitive CRP depending on what my client has in terms of previous markers, ESR, ferritin, LDH. And I usually do run isoenzymes if I can get a proper blood draw. We do use lymphocyte to neutrophil to lymphocyte ratio, NLR, and ideally should be either 2.5 and I'll talk you through a couple of studies on that. And the up and coming marker that's been used in the last few years is PLR, so that's platelet to lymphocyte ratio. And we want to try and keep that under about 160. And study ranges use things like 170 to 200 is cut off. But it seems to be the most recent papers use about 160 as a cutoff for PLR. Always measure vitamin D levels. I know you will be, but this is essential for immune regulation. We might want to have a look at looking at oxidative stress markers, obviously not during chemotherapy or radiotherapy treatment, but say if we're looking maybe three to six months down the line, we want to see if actually we're trying to return to some kind of homeostasis and our antioxidant system's working well now. And we use things like 8-hydroxyde-DG and lipid peroxides, and that's really markers for any particular needs for water and fat-soluble antioxidants. SNPs will play a role. You will get them as a part of DNA health or Life Code GX nutrient profiles. And so we've got to remember, though, that SNPs are always, always about risk. They're always about potential risk, but they're not about current biochemical status. So do use them, but don't over rely on them either. And particular SNPs that are relevant to us within this setting is IL-1, IL-6 and TNF-alpha. And some profiles also have CRP SNPs. So NLR or neutrophil to lymphocyte ratio and cancer. There was a really big umbrella meta-analysis in 2020 that showed a very strong evidence of association between NLR and outcomes in a number of solid cancers and particularly also cancers treated with immunotherapy as well. So NLR cut-offs in various studies vary hugely, you know, from 1.9 to 5, which is a rather big difference. But most recent studies use cut-offs from just under 2.5, so it was one with 2.461, which is a very specific number, up to three. In a breast cancer meta-analysis in 2017, we found that when we used the median cut-off value for high NLI was around about three for the studies that were reporting an impact on overall survival, which is OS, and about 2.5, which was in the studies reporting DFS, which is disease-free survival outcomes. So I tend to go for 2.5 in my own practice because of that. And there were two other meta-analyses for breast cancer that shows that high NLR is associated with a diverse overall survival and disease-free survival in patients with breast cancer, and it's particularly impactful in triple negatives. So really, really important to get the NLR spot on. And studies are now combining NLRs, the neutrophil to lymphocyte ratio, with PLR, platelet to lymphocyte ratio, to assess immune balance. So in 2019 breast cancer study they actually looked at pathological complete response and that's PCR and whether that was actually impacted by immune status of cancer patients and they did find that definitely was impactful. So patients had low NLR and low PLR so the idea of that was that they didn't have a particularly pro-inflammatory tumour environment. They actually achieved a significantly higher rate of complete pathological response compared to those who had high NLR or high PLR, and therefore they're indicators of a more pro-inflammatory tumour microenvironment and more chronic inflammation in general, really. In 2019, there was a breast cancer meta-analysis which explored the role of platelet-to-lympho-situation predicting overall survival. And it definitely showed that elevated platelet to lymphocyte ratio was associated with a shorter disease-free survival. So it's an important marker for us that we can get very simply from full blood counts that are run on our patients and clients to be able to assess what's going on with their inflammatory status and what can we do for them to be able to address that. So the The other thing to think about is this just requires a full blood count, which is easy to do. And don't forget that it's far less relevant during chemotherapy because it will be skewing your NLR already because it might be preferentially down-regulating neutrophils. So it doesn't mean that someone has perfect NLR. It just means that actually they're being messed around with chemotherapy. So ideally you want to get a... the NPLI diagnosis and have a look at what they were like before that and then after something like chemotherapy or radiotherapy is completed then again you would want to look at full recovery to normal ratio that's that's really important. LDH so why on earth do we measure LDH in terms of thinking about inflammation in tumor microenvironment because it's actually a metabolic marker so the reason we do it is because LDH and the resulting lactate is really the metabolic link between tumor cells and tumor microenvironment. So lactate is produced as a result of the Warburg effect in the tumor cells because they actually undergo aerobic glycolysis. But it's not only produced as a byproduct of the metabolism, it's also a key molecule in carcinogenesis and tumor immune evasion. It's an immune suppressant in a tumor microenvironment. So apart from being a marker of the metabolic status, it has a significant prognostic predictor of overall survival, it's really important for us. So, and the other things to think about is that serum LDH can also serve as a predictive response to chemotherapy. So in TNBC for example, I use it quite a lot just because there's been more data within that, but there was a strong association found between serum LDH levels, high number of metastatic sites and poor prognosis. And there was a reduced progression-free survival and predicted poor overall survival and poor response to chemotherapy. So we want to make sure that LDH is down to normal levels as much as we can do. And this doesn't just extend to breast cancer. There have been a number of different studies in various other solid tumours. Actually LDH is also used in blood malignancies as well as part of their markers. So lactate is important because when the tumour associated immune cells produce lactate, they will not only acidify the tumour microenvironment and cause it to become more immunosuppressive, but it also facilitates... metastatic dissemination and therapy resistance so it is important for us to keep an eye on that LDH if we can. So in terms of how we're going to address this now we've tested we've done our CRP ESR hopefully got an LDH looked at some vitamin D and some of the other markers that we talked about What do we want to do about it now? And the key thing is, as I always say, don't forget to look at the root causes and factors in the chronic inflammation immune dysregulation. So sometimes people will assume that it's normal to have really high inflammatory markers when you have cancer, and metastatic cancer in particular. And actually it's slightly turned around on its head. We need to be able to try and get that inflammation down so that we can try and have better response to treatment. and promote better immune control within our cancer clients. So the key thing that you want to look about is what's causing and driving this chronic inflammation. Food is really important to assess, as we know. So diet like standard American diet or standard British diet with its poor omega-6 to omega-3 ratio, toxic oxidized fats, high saturated fat and low fiber promoting dysbiosis, which will play into inflammation. Acrylamide from highly processed. carb foods cooked at high temperatures, high sugar and that's age-rage interactions driving inflammation, poor dietary antioxidant intake including all the phytonutrients, pesticides and additives and nutritional deficiencies and that includes vitamin D and again a number of other nutrients that we know are important for healthy immune function and immune regulation. Sometimes if you have someone who's you're not sure about the omega-6 to omega-3 ratio then it's very quite useful to do a proper blood spot on them and have a look at their fat ratios. Dysbiosis can drive chronic inflammation, it's a factor I see play a massive role in many of my cancer clients and infections, toxins, drugs and alcohol, stress, trauma and sleep disruption are pro-inflammatory and lack of appropriate physical activity or excessive physical activity without adequate rest. So they are all factors to consider. when we're looking at why is someone inflamed, why does someone have an elevated CRP or ESR or other markers. So interventions. Interventions particularly are split here into things we want to do from the inflammatory point of view and things that we might want to do to try and support a specific anti-tumor response. So always start with lifestyle and inflammation. You would have heard from me a number of times, but I will reiterate it. So your anti-inflammatory whole food diet. with correct omega-3 to omega-6 ratio, high phytonutrient index from vegetables, low sugar fruit, particularly polyphenol rich berries, herbs and spices, appropriate fasting, sleep, movement and stress management. So particularly attention in terms of herbs and spices are we know all about turmeric, we've all heard about it, particularly consumed with fat plus or minus black pepper depending on how good the gut is at that point. and how irritated the upper GI tract is because I wouldn't use it if someone has castritis for example. Ginger, rosemary, saffron, chili, all sorts but most herbs and spices basically contain antioxidant anti-inflammatory compounds so for example parsley contains very valuable flavonoid compounds called epigenin, quercetin and luteolin. So pretty much the more the merrier and the more diversity and variety you can get the better. It's not about overdoing one thing, so just overdoing the turmeric, but actually it's all about just trying to have a balance and a mix of the different compounds. Herbal teas with anti-inflammatory and antioxidant effects, there are again plenty of them, most of them have an anti-inflammatory and antioxidant effect, but green tea, gynostemma, tulsi and ginger are particularly worthwhile mentioning. Intermittent fasting or caloric restriction is anti-inflammatory, and the latter is obviously less popular. We do tend to opt for intermittent fasting. Don't overdo the fasting if the patient is losing weight or has a low BMI. It's not appropriate for BMI on day 18. There are different regimes, of course, we know about fasting mimicking diet, extended overnight fasts of 13 to 14 hours, 16-8 time restricted feeding or fasting days. So it just depends on your individual clinical assessment of what you think your client will be able to manage and also how metabolically dysregulated they are. So treat the root cause always, so we're not just going to be slapping on anti-inflammatory interventions because we need to actually unplug the inflammation at its cause. So we're not going to be just mopping the floor, you need to turn off the tap. So for example, treat the dysbiosis, if there are infections driving it, if there's anything else driving this inflammation, you need to treat it, remove it or tackle it in some way. And as I said, it's often assumed that high inflammatory markers are a consequence of cancer, but it's not always the case and you do need to look at other factors. So specific interventions we might consider, we might want to look at omega-3 and vitamin D is just the basics, you know D3 ideally would be combined with K2 unless you're on anti-oculants like warfarin for example. You would want to use antioxidants as appropriate, so always food first, don't forget that's where we should be deriving most of our antioxidants and the widest variety of phytogenes you can get. The one antioxidant I will occasionally use in combination with Active therapy, active treatments, tocotrienols, they can be very useful. But no other high-dose antioxidant supplementation during chemotherapy until proven otherwise. And of course, other specific antioxidants that we know in specific cases are just like a prostate cancer. But again, food first still. I would normally get people to have one or two tablespoons of tomato puree with some extra virgin olive oil instead of trying to shovel a whole ton of lycopene down them. Most commonly used supplements that we use in this particular case, and again there are plenty more, this is just a small selection that have some data in cancer and that people have used clinically, but it is just a tiny bit that we can have a look at. Curcumin, obviously we know that's one of the most popular ones for a very good reason, but caution in significantly elevated LFTs, if you do find liver function enzymes are really going off, then you will. might want to decrease your curcumin dose significantly because it can make people feel really quite a lot more nauseous. Black cumin seed and agela sativa is a rich source of thymoquinone and is a beautiful anti-inflammatory and immunomodulator. I use it a lot. Willow bark is herbal aspirin basically in the Cox inhibitor so that's a context in which we use that but much kinder on the GI lining. Specific polyphenols is appropriate, resveratrol, EGCG, etc. There's plenty of those and some people will use CBD oil as well, which has multiple different mechanisms of action to it. So tocotrienols in cancer, so one antioxidant where actually you can combine it with certain therapies, not necessarily every single therapy, but it might be useful in some active cancer treatment. So gamma and delta tocotrienols specifically. have the highest anti-cancer activity and target a whole number of pathways. For example, inhibiting cell cycle, induction of apoptosis and autophagy, inhibition of invasion metastasis and angiogenesis. And actually what's really interesting is that tocotrienols appear to synergize with both pharmaceutical antitumor agents such as chemotherapy, statins and some of the other targeted therapies or natural compounds again with EGCG, resveratrol, ferulic acid for example. So It's a really important tool that's very useful for us. And it's important that we use gamma and delta tocotrienols, not just in general vitamin E. As we know, most vitamin E in supplements is not such a great quality and relies heavily on alpha-tocopherol, for example, instead of the tocotrienols, which are the truly valuable compounds. We've got to remember that tocotrienols and tocopherols often compete for absorption. So actually it would be better to give tocotrienols alone rather than in combined formulae. There was a phase 2 trial of bevacizumab, which is an anti-VEGF drug, combined with tocotrienols in chemotherapy of refractory ovarian cancer. And what was amazing in that is the rate of disease stabilisation was 70%. So that's 70% of those patients with ovarian cancer which did not respond to chemotherapy stabilised on... Bevacizumab with tocotrienols with very low toxicity and the median progression free survival was about seven months and overall survival was about 11 months and this is late stage ovarian cancer and this is high compared to the current literature so it was significantly synergistic in this combination certainly something to consider and there are multiple studies mainly in cells and animals that showing effects on NF-kappa b synergy with the different chemotherapy agents and reversal of multi-drug resistant, as well as inhibition of the stemness, which is a stem cell property in cancer stem cells. And a number of things that we might want to consider about when thinking about JAK-STAT pathway, which we talked about as a really key driver, you know, talking back to the beginning of the lecture where we said IL-6. kind of JAK-STAT and then you also have the other interaction with NF-kappa-B as well. So number of different compounds is a huge amount to choose from that interferes with things in different components of this JAK-STAT pathway from the top to the bottom and there are a number of them that act at specific at several different points so for example EGCG acts at the point of the top bit as well as the bottom bit in terms of the target genes. You also find that resveratrol and curcumin will act in a number of different parts of the pathway. Let's talk a little bit about polyphenols because polyphenols have significant anti-inflammatory and antioxidant actions. And I think it's important for us to get a bit of clarity about what polyphenols actually are. So polyphenols include two different groups. They're plant-derived compounds that include two different groups of chemicals, non-flavonoids and flavonoids. So non-flavonoids chemical compounds that exist within plants include HBA and HCA and still beans. And they're the ones we hear quite a lot about, and that's terastilbene and resveratrol in particular. Then we look at flavonoids in a number of different groups. Flavanols, such as EGCG, that's a very popular one, of course, as we know, within cancer support. Flavanols, and that's quercetin, camphorol, and muricetin. Isoflavones as we know in terms of being soy derived, genistein, diazine, anthocyanidins and number of those around and flavonoids and that's hesperidin and noreginin and they're really quite a lot more enriched in the citrus fruit in particular. So there are some specific antioxidant flavonoids that are useful in the context of cancer for multiple different effects but particularly things like EGCG, genistein, diazine are used quite a lot. quercetin, apigenin, christian and luteolin and many many others. The above are just the most studied and I will share a paper on the learning platform that talks you through all the various compounds and kind of where they come from and how they might be helpful and some of the evidence around those. So I want to just highlight a few specific whole foods that as well as plant extracts that can be quite useful. To use and see ginger is anti-inflammatory, it also has anti-proliferative and anti-tumor activities and what we do know is a ginger extract in six gingerol which is one of the compounds found in ginger they actually they activate Nrf2, they decrease activation of TNF alpha, ROS and F-kappa B and COX-2 pathways and there are different options for using ginger you know always use it in food ginger decoction and I find that generally The herbs, leafy herbs in general, we think about in herbalism are better brewed as tea, but roots really need to be decocted, which means actually boiled in boiling water for a little bit of time to be able to extract all the different compounds within it. And we want to try and keep the lid on so we don't let too many of the lovely volatile chemicals escape, so sort of try and do it with a partially sharp lid when you do the decoction. So plain tea, plain ginger tea is fine, it doesn't achieve maximal extraction so ideally you'd want to decoct your grated ginger for about 10 minutes if possible and we of course can also use it as a supplement. Not forgetting the fact that also ginger can have other effects in terms of being supportive to the gut and reducing nausea so a number of ways of using it to support our clients with cancer. Curcumin, I mean what doesn't it do really should be the question. So, of course, within this particular talk, we are going to remind ourselves that curcumin has been demonstrated to have a significant anti-inflammatory effect through multiple different signaling pathways, including NF-kappa B, JAK-STAT, and TGF-beta pathways. And so it also activates, of course, as we know, the apoptotic pathways and inhibits inflammation, geogenesis, and metastasis. And a number of things that we'll also target that are to do with... Apoptosis is things to do with p53, RAS which is more about driving cell proliferation, PA3K and PKB which are involved in the metabolic side of things, and beta-catenin and Wnt and mTOR which are involved in both metabolic but also the stem cell pathways. The other things to say is that curcumin of course goes broader than that and also exerts beneficial effects on cancer treatment related toxicities such as kidney toxicity, cardiotoxicity and toxicity to the nervous system. So it's a very useful multi-agent to use in a number of different settings. In terms of which curcumin, I mean, there are so many formulations in the market. At one point, I will do a review which one are the most kind of bioavailable and dosing, etc. But what we do know is that Lipocirc and Meriva have been studied in cancer specifically. And Meriva is a... Lethizynized formulation of curcumin for better bioavailability and you can get a soy-free version as well. So just a quick reminder the fact that curcumin has been found to work alongside chemotherapies in a number of different settings including prostate cancer, liver cancer, gastric cancer, blood and colorectal. So something to keep in mind, the fact that it's a compound that has been used alongside some of the active chemotherapy drugs. And there are many, many ongoing trials with curcumin. Here's just a tiny, tiny selection, but there are a number of them and you can see they're being used in combination with chemotherapy quite a lot of the time or after significant interventions like prostatectomy. So it's really important and even in the prevention setting there's actually a trial for nano emulsion of curcumin for obesity, inflammation, breast cancer prevention so it'd be interesting to see where that shows up. So if you are trying to use it within a specific setting just put curcumin and whatever drug of choice your client is on in PubMed and see if there been any studies on the combination because it might be useful to you to have that as a backup. Black cumin seed or Nigella sativa and inflammation cancer. Thymoquinone is a major active constituent of black cumin seed and has a huge number of different effects. There are a number of ways in which thymoquinone mediates cancer activity. It will affect p53, NF-kB, STAT3 which we talked about as major pro-inflammatory drivers. It will also affect the nutrient metabolic sensing mechanisms and it will affect the pro-growth and pro-proliferation signaling pathways such as PI3K and ACT. So you can see a number of different molecules are being affected here and there's also early evidence around enhancement of NK cell-mediated cytotoxicity so maybe instead of an anti-inflammatory it's actually more of an immunomodulator something like medicinal mushrooms. So talking about medicinal mushrooms, we are now moving on from just doing anti-inflammatory interventions to thinking about supporting anti-tumor response. And so specifically, we're going to talk about medicinal mushrooms PSK and two other mushroom products licensed in the Far East for supportive care during cancer treatment. There's astragalus membranaceus, which is a wonderful TCM herb that's used to support systemic immunity and ameliorate immunosuppression. It actually activates the... T-cell tumour kill function and M1 macrophages in the tumour microenvironment. And there's some very early studies in andrographis as well. Medically, of course, they use immunotherapy, and we know that particularly with the checkpoint inhibitors, we need a healthy gut microbiome, and they do carry a risk of new onset autoimmunity, which is tricky. Ideally, from the medical point of view, the medics would minimise steroids unless absolutely necessary because you're suppressing tumour-specific immunity anyway. And you might want to consider gastro-resistant aspirin, particularly in colorectal cancer. So that's really with regard to Cox inhibition. And there's a caution with NSAIDs. Again, NSAIDs are quite overused within the cancer setting. And while they do have some beneficial effects, there are other ways of inhibiting the same pathways without risking GI toxicity and kidney toxicity from NSAID overuse. And of course the other interventions are out of scope for nutrition professionals but you can also refer to for mistletoe to optimize quality of life and support immune system balance and LDN is also used off-label for immunomodulation. So mistletoe therapy part of the way it works is immunomodulatory lectins and a number of different brands like Iscador, Helixor and Obnobufraxine and it must be at minimum subcutaneous and there's no proper really good data on oral even though Royal London Hospital for Integrative Medicine insists on using mostly oral but actually having done an evidence review I see very little evidence for this but much better evidence for subcutaneous injection and it's offered by a number of different integrative medicine doctors and there's a major centre in Scotland called Camp Hill Wellbeing which is well worth referring to. It's not always appropriate straight away. It's one of those things whereby people just get thrown onto mistletoe but when you have very high inflammatory markers, when I have some of my patients who have CRPs of in excess of 150 or 200 or someone's ESI is 80, you really don't want to be waiting in there with mistletoe first. You want to try and reduce the inflammation a bit before you get mistletoe started or starting at a very very low doses. And it's not appropriate if you've got active brain mets with cerebral edema and there's room for argument for whether you can do it in other cases after treatment for the metastases. In terms of summary, just to remind you that our key goals are to decrease inflammation, oxidative stress, support immune surveillance and a balanced specific anti-tumor response. and that's trying to get that Th1 polarisation away from the Th2 in immunosuppressive environment the tumour is trying to generate. For assessment, at minimum, get neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, easy to do from full blood count, vitamin D, CRP and ferritin, and if you can get it, try and add ESI and LDH because they're useful. Look at root causes appropriate excess oxidative stress if you're looking at three to six months post active therapy and review SNPs in the wider panels just to see whether the person is more likely to exhibit an exaggerated inflammatory response. Support of course we talked about the anti-inflammatory whole food based diet rich in phytonutrients. We do need to incorporate dietary mushrooms you'll get a new lecture on mushrooms shortly and of course the herbs and spices. Anti-inflammatory other lifestyle interventions combining nutrition with fasting, appropriate movements, supplementation, stress management, don't forget to check your interactions with your supplements, and supporting immune surveillance and anti-tumor responses for us will include things like medicinal mushrooms and astragalus. We can argue about whether nigella sativa or black cumin seed belongs in this category as well, and consider referral for other therapies if more support is needed. Thank you very much for listening. ________________ 3.6 Effective and balanced detoxification so detoxification and cancer just a quick reminder of where we're at on our systems wheel so we've already covered mental emotion spiritual health and biorhythms microbiomes and gi function balanced immune function now moving into effective and balanced detoxification so the aims within this particular you system is really to manage exposures by reducing toxic load and that's through air, water, food, cosmetics, home products and any other aspects of the exposome that we need to target and promote normal balanced detoxification processes as appropriate to the clinical situation cancer type and without interfering with medications. So the exposome is a really wonderful concept, it's the integrated function of exposure on our body including everything. what we eat and do, our experiences, where we live and work. It covers ecosystems, all of our lifestyle, including activity, food, sleep, drug, smoking and alcohol use, social exposures and physical and chemical parts of the exposome. And this particular chemical part is what we're going to be focusing on here. And it's an important integral part of this. So it will cover anything from. you know, temperature and light and noise, two typical chemical pollutants that we are used to talking about, as well as things as soil contaminants, drinking water contaminants, and air pollution as well. So it's really important for us to look at it. And we're going to be focusing specifically on the physical chemical part of the exposure in here. And I'm actually not going to be covering as much of the physics here, but really focusing on the chemical. So the evidence of environmental exposures in cancer is just a small selection here. We could go on about it for quite some time and I do delve into it more deeply in the advanced practice modules for specific cancers, but we have quite a few well-documented and accepted links. So for example, lung cancer risk and smoking air pollution radon exposure, mesothelioma, which is cancer of the sort of pleural and peritoneal lining and asbestos exposure. And secondary cancers following chemotherapy and radiotherapy. They're usually haematological in terms of chemotherapy and use of alkylating agents or local scatter from radiation effects also inducing cancer formation. So quite a few well-documented links that we know already. There's some developing or lesser-known associations, so things like specific insecticides or pesticides and haematological malignancies, particularly in children. And paediatric leukaemia risk is also linked to solvent exposures. There have been a number of different studies on breast cancer and endocrine-disrupting chemicals, and there's a few listed here, as well as air pollution and exposure to solvents. And what's also interesting is that we're also seeing organochlorine pesticides and chromium exposure into prostate cancer risk as well. pasted in a useful lecture from ZRT labs, as you do keep in mind it is commercial, but something to consider about cadmium and metalloestrogens in breast cancer. And do know the evidence is still developing, it's not really clear-cut. So in terms of breast cancer and chemical exposures, I've just highlighted three of the solvents that we're kind of used to linking to increased breast cancer risk. We know about alcohol and we've covered that. quite extensively in the epidemiology it's really important to remember that yeah alcohol consumption does include increase estrogen levels and it is a carcinogen and particularly the with the metabolite called acetaldehyde that arises from alcohol benzene as a solvent has also been labelled as a carcinogen and and produces increased memory carcinomas many animal studies And it might have potential interaction with certain CYP SNPs, as you can see from here. And methylene chloride is another one that again has been linked more as a possible carcinogen rather than a defined one. A few other additional chemicals with occupational exposure. This is relevant to breast cancer because there's been a recent big breast cancer review and looking at occupational exposures and chemical exposures. And. the links and the evidence to development of breast cancer. So you don't need to know all about this in particular detail unless breast cancer is your specialty, but it's just to be aware of the fact that there's a whole number of things that we need to be considering, anything from styrene in terms of... plastics and rubber production and paints and adhesives to acrylamide where you deep fry starchy foods. So there's quite a range of toxins and carcinogens to consider. What I like about one of the papers I found recently is this relatively simple diagram about thinking about how these different chemicals might affect EMT or epithelial mesenchymal transition where the cancer cell might go from being relatively static and contained with this environment to becoming a sort of a crawling invasive migratory cell. So what we do know is that there are actually roles for pesticides, toxic metals and endocrine disrupting chemicals within that setting. And there is some very early thought around the cancer stem cells being also linked to... phthalate, bisphenol and cadmium exposure. So things to watch. I would say that the evidence is in no way definitive, but we do need to keep those in mind and try and reduce exposures in our clients whenever possible. So how do you assess whether this particular thing is relevant? And we need to take a detailed history of previous and current exposures. have included TQ, which is toxin exposure questionnaire from the IFM in your resources. You can develop your own as well. It is important that we do take a really good toxic exposure history. And then you test if relevant given the history, depending on what you've established by your problem. So heavy metals and minerals, and you do have to test the two together because there is a balance between nutrient minerals and toxic metals. So assessing one without the other is just going into it blindly. POPs or persistent organic pollutants again might need to be assessed. Microtoxins if it's relevant and radon in certain areas of the UK as relevant to the radon map and there's actually a way of just hiring the radon meter for three months via the UK radon service if your clients might want to do that. This is just a quick reminder where the high radon risk areas are in the UK and there is an interactive map online which you can check your own postcode or your own area as well. And just to mention about radon before we move on to testing, it's actually not just relevant to lung cancer risk, it is relevant to things like breast cancer risk as well, so it isn't as simple as an inhalant toxicity only to the lungs. So if you did want to test environmental exposures, what options do you have? And Great Plains Laboratory really offers probably most extensive options in terms of environmental exposures. There are other labs, of course, but that's the ones that I tend to use most often. GPL-TOX is the sort of organic pollutants and it covers markers for a number of different chemicals. It does a separate glyphosate test or you might want to add it onto the GPL-TOX. And you can also order mycotoxin profile. In terms of where to get these tests, you can register with Great Plains directly. It's available for some practitioners. Or you can get them from Biolab, which is at the moment the best pricing in the UK for these tests. And you can get them at slightly higher prices from Nordic or Regeneris as well. So again, a number of options for you to consider depending on how you work in your practice. In terms of looking at heavy metals and elements, again, a number of different things. I tend to use it at T-Labs quite a bit because I like the fact they do a blood spot and a urine profile. Because when you look at different metals and elements, you want to look for them in different compartments of the body. They're not all going to show up reliably in the bloodstream. You know, there's not much point in doing. a blood spot iodine for example you do need a urinary sample for that it tends to while it's not a perfect marker it tends to be a more reliable marker anyway so i tend to like the comprehensive toxic and essential elements prefer from zodiac seal labs. They use it quite a bit. But Genova offers elemental analysis, which is blood only and combines toxic metals and nutrient metals. Obviously, they also offer urinary panels as well. Just be mindful of the fact that they are significant. affected by your previous nutrient intake in terms of your last meal, etc. And again, there are other labs, just these are the ones that I tend to use most often. A quick reminder of phase one and phase two as we head into the next section of this talk. And as we know, there's phase one, phase two, and of course, phase three in the gut. And phase one is really designed to take a toxin and almost activated and to make it a bit more polar so that it can be gotten rid of by the body a little bit more easily but it might create toxic intermediary metabolites and we need the phase two to do the conjugation to really get rid of things safely really make them proper excretory derivatives that then go into the body like sweetened in feces or go into the serum might be excreted in the urine via the kidneys. So I liken it to a toxin is a little bit like a grenade. You know, phase one basically takes the clip out and you've got a loaded grenade and phase two throws it away from you. So it's important we're not standing there with a loaded grenade when we've just got an hyperactive phase one or overactive phase one. and a phase two that's really struggling because of either combination of genes or genetics and environment or the fact that we've got we are quite nutritionally depleted. So it's important for us to consider that. In terms of genetic contributions, again, as a part of your assessment, you might have assessed that toxic loads through the questionnaire, might be some testing. You might want to look at the genetic contributions of. how well detoxification in terms of phase one and phase two enzymes function in this particular person. And so there are a number of different panels that do SNPs for phase one and phase two, and it's not a single variant, but the combination that's most important. So it's not one single thing that's going to give you a significant increased risk. It's often a part of the pathway combination or combination of different hits in the system. And currently the best widely available is LifeCo GX detoxification profile specifically for that. However, as I'll cover in a second, we are doing a more specific profile. Nutrition genome. in the US also does some of the SNPs relevant to detox, but they do quite random selection. Pharmacogenomics is also important, more really from the medical perspective, I guess, than from nutritional therapy perspective, but it can be relevant and useful for you guys to be aware of it. And there is a med check option via sort of DNA Life and that can be added to things like DNA health profiles. So I have created a new custom SNP panel that will be adjusted probably annually or every every couple of years to include new SNPs and new markers depending on the research in the area and it's going to be called a Neutrogenetic Systems Panel. It'll be available via DNA Live through Nordic. At the moment we have developed it to be available in a package with DNA Health, MedCheck, DNA Estrogen all together at £4.95 and it will include A whole panel of phase one, phase two extended SNPs and actually going to be more covered than what we've got in the Life Code GS detoxification profile. We'll also have DNA integrity SNPs and ATM and p53. We'll probably add MDM2 into that as well at some point. And some of the ESR1 SNPs that are currently missing from the DNA estrogen panel. And we will probably do a version that is probably in the future more targeted at hormone-driven cancers versus non-hormone-driven cancers. But this is something I've created that's still going to be relevant for a number of our patients and clients. And we can see if we can... make it cheaper by removing DNA estrogens for those of you who really work with non-hormone driven cancers. It's going to be a simple report, just plus minus on the SNPs, but there will be a comprehensive guide provided by us. So through my systems approach to cancer program, it will be produced by NutriGenetics postdoc in collaboration with me. So we will make it informative and clinically relevant for you guys. So if we're thinking about examples of SNP links to cancer risk, so what we need to think about the SNPs might be associated with either increased or decreased disease risk in terms of cancer, as well as actually impacting the effectiveness of their interventions. So it might actually be providing an additional vulnerability that might be explored by current new therapies for example or it might be inhibiting the effectiveness of the intervention or making something more toxic and that's where pharmacogenomics is important in looking at SNPs and the impact on drug mortality metabolism with its activation of the drug, like tamoxifen being converted into endoxifen by CYP2D6, or inactivation of the drug. There are a number of different tyrosine kinase inhibitors that interact with a number of CYP enzymes, and that can significantly affect the clinical effectiveness of that drug in the setting that you are applying it. As well as Actually impacting side effects as well, there's some work going on about SNPs and side effects and whether there's unacceptable toxicity. And there's things that we already know that are used in clinical practice quite a bit in terms of genotyping for 5FU and DPD, for example, in colorectal cancer that's done quite a lot now. Phase 1, for example, there are CYP enzymes or combinations, and as I said, it's really important to not focus on a single SNP. It's usually the combination that confers significantly increased risk. But there have been several CYP1A1 SNPs that are linked to increased cervical cancer risk, and also a genetic SNP in CYP1A1 called MSPL, which... actually plays a role in increased risk of head and neck cancers, particularly in combination smoking, which makes sense because CYP1A1 is involved in bioactivating polycyclic aromatic hydrocarbons into carcinogenic metabolites. Remember, you've actually taken the pin out of the grenade. Now you're standing there with a loaded grenade. There's also significant association with breast cancer risk that have been observed among women with a combination of these different phase 1 and phase 2 SNPs, for example. So that's CYP1B1, which increases the production of the 4-hydroxyestrogens, which then go on to make DNA damaging quinones. and COMT, which is one of the phase two enzymes that we need to methylate and detox those oestrogen metabolites. And also looking at COMT and MnSOD. So again, if the methylation isn't working properly, but also we don't have the SOD to be able to mitigate the damage that comes from the quinone production, then again, it increases your risk of breast cancer here. In terms of phase two enzymes, enzymes and number of glucuronidation enzymes that have been identified in terms of the polymorphism in UGT1A and UGT2B genes, but there's also other different ones and you can see there are a number of different UGT enzymes. And they have been linked to a wide variety of cancers in terms of risk factors, bladder, breast, colorectal, endometrial, esophageal, head and neck, liver, lung, prostate and thyroid. We're not entirely sure whether all of these polymorphisms are actually cancer causative per se, or are they actually linked to something else? Is there a confounding factor that's linked to these that might actually be the causative thing? We do know what's quite interesting is there are specific combinations of these enzyme SNPs that might significantly increase the risk of colorectal cancer. I mean, by really the three SNP genotype increase in risk of nearly four times. And actually, if you combine these with specifically targeted interventions like NSAIDs, aspirin or ibuprofen, you might be able to find there is a way of mitigating that risk and doing a bit of targeted chemo prevention. Obviously, I know it's not relevant from a nutritional survey perspective because they're medications, but this is something to watch because we might be able to again personalise chemo prevention, which is an area that I'm really interested in. It's about looking at precision health for people, not just identifying people at risk and going, oh, whoops, you're at risk, let's screen you more. But can we intervene and can we intervene not just with pharmaceuticals, but can we also intervene with natural substances as chemo preventers? So GST we know this is going to be a big one because glutathione is conjugation is such an important pathway within our phase 2 metabolism and there has been a number of different studies that are covering the three different GST or glutathione S, sorry, glutathione S transferase enzymes. And we've got three of those. We've got GST-T, GST-M and GST-P. So there are three different GST enzymes. And you can have a deletion in a number of those. So GSTM1 and GSTT1 null genotypes, that means deletions, they confer additional risk for colorectal cancer in Caucasian populations. And what's interesting is then there is also some of the potentially protective mechanism as well as increased risk mechanism. So GSTT1 deletion is associated with increased risk of recurrence in breast cancer. What's interesting about GSTM1 is that GSTT1 deletion is associated with increased risk of recurrence in breast cancer. STM1, that's been associated with a worse grade in presentation, so much more likely to present with grade 3. But if you are presenting with an estrogen or progesterone positive and HER2 negative subtype of breast cancer, you might actually have a reduced... recurrence risk, which is interesting, and we're not really sure of the mechanism for that. GSTP-1 is an enzyme that's been significantly investigating a number of different cancers, as you can see from this table here. And there's three-fold to five-fold increased cancer risks for different breast cancer mutations. slash SNPs associated with a GSTP-specific genotype. So what we've got to realize, it won't be one SNP that will be causing all the trouble. It was likely a combination of SNPs that will affect the function of the enzyme to a significant enough degree to confer increased risk. And also, if you have multiple hits within the same pathway, it's much more likely that this risk is actually going to be clinically significant enough to make a difference. NAT or NAT and acetyltransferases, NAT1 and NAT2, have also been linked to a number of different cancer types, in particular colorectal cancer. And there have been conflicting studies because some studies don't find association with NAT2 genotype, depending on the SNPs they use, and some places do. So one of the studies found actually Fried red meat, alcohol, smoking increase the risk of sporadic colorectal cancer, particularly colon cancer, not just in and of themselves, but if you are rapid acetylator, it can increase your risk eight to tenfold. So that's quite a significant difference. So let's think about, we've done our assessment, we've done our toxin exposure questionnaire, we've quizzed them about the eat. toxin exposures, we've identified the key pressure points in their system, we might have done some targeted testing if that's warranted, if there's budget, and now we want to have a look at how we're going to manage their exposures. And here we look at sort of I've adapted the 5R into a 6R program for supporting effective and balanced detoxification. Stage one is really always going to be removing, reducing and replacing and that Remove and reduce environmental exposures and replace these with healthier non-toxic alternatives. That's most important because it doesn't matter what kind of detoxification support you do downstream. If you haven't turned off the tap upstream, you're going to be struggling. Stage two is replenishing and rebalance. And that's replenish nutrients necessary for healthy GI, liver and kidney function. And rebalance phase one and phase two detoxification. Address phase three, of course, as well, if necessary. And stage three, or RENEW, is applicable in a small proportion of our clients with cancer. And if and when necessary, you can want to consider more target intervention-directed key embedded exposures. So if you do see that someone's got a massive mercury toxic load, you might need to tackle that at some point, but not before you do stage one and stage two adequately, and also not when they're going through an active cancer process, because it would be too much. So when we're looking at remove, reduce and replace, we're going to look at every part of the physical chemical exposure. And that's looking at air, so filtration, dehumidifying if someone's living in a dump house, getting rid of mold if there is some mold, water filtration, your Berkey, your reverse osmosis with mineral ad back, food, looking at not only of course our usual baseline of an anti-inflammatory whole food based diet, which we've already talked about, But also looking at the dirty dozen clean 15 at minimum if not already largely organic. Organic certainly for animal products is an absolute must and small wild fish only not farmed and it's important to avoid toxic exposures and pollutants. Avoiding plastic wrapped products and watching aflatoxin sources particularly peanut and this is really relevant for the risk of hepatocellular carcinoma and liver cancer because aflatoxin is particularly. potent in this population. When we're looking at the home, we might be looking at the kitchen, trying to get away from plastic of any kind as much as possible, never heating food in plastic, avoiding damaged or refined oils, looking at cooking methods because we want people to never deep fry and to try and avoid high temperature cooking methods in favour of lower temperature cooking methods, trying to steam frying. or if they are using high temperature cooking methods, using them in limited amounts with the right oils. Personal care and cleaning products, all of those need to be cleaned up as well as other things in terms of trying not to buy things with lots of flame retardants, lots of plastic stuff in the house. And there's Think Dirty and environmental working groups, Skin Deep databases and apps available. So again, you can send your clients that way to try and get them to see if they can detox their home environment. And I've included a worksheet on reducing toxic exposures from IFM in your resources as well. And there are also occupational exposures to consider. And they're the trickiest because not everybody can change their job. And the other thing to say is sometimes when the environment is really, truly toxic, sometimes a home move or a lateral career move really does have to be considered. And it's obviously not always possible. We can't get the situation 100% perfect, but it is important that we do consider these very carefully. There are also, of course, aspects of the physical exposure that I haven't highlighted here, and that's really things to do with more like... EMF and noise exposures and some of the other exposures. And again, we want to generally try and keep the environment as calm and conducive to balanced physiology as possible. But I haven't covered them here specifically because I'm focusing much more on the liver metabolism side of things and chemical exposures. So stage two replenishment, rebalance and replenish, it's really important that we are ensuring adequate but not excessive protein intake. One of the worst things that sometimes our clients can do is suddenly go from a varied diet to going on to just vegetable soups, for example. There's nothing wrong with vegetable soups. I love vegetable soups. But if they're not consuming any proper protein, they're going to struggle to detoxify. And particularly during things like chemotherapy, where they need the protein for the tissue repair. As we always talk about wide spectrum of dietary antioxidants from daily rainbow of colorful plant foods, herbs and spices, and the more the better, trying to ensure they eat 50 different plant foods per week and in rainbow colors, ensuring good supply of blue, purple berries, allium and cruciferous vegetables because they're by functional modulators. They actually balance phase one and phase two quite often. So in Rebalance there are specific targeted interventions aimed at specific phase one, phase two pathways and you can look at them in the IFM Detox Guide. I'm not going to reinvent the wheel here, it's important that we use information that's already available. And as I said it's important for us to focus on foods that balance phase one and phase two and what we want is a balanced activity. We don't want excessive phase one that's activating our toxins and giving us a loaded grave with a pin out. We want this to be balanced with phase two that's effective, that actually throws a grenade away from us. So it's really really important that we try and balance the two things together. We want a normally active phase one and normally active phase two. We don't want things to get stuck in the middle. Those reactive intermediary metabolites are the most dangerous ones quite often. So here cruciferous and allium vegetables and that's your onion and garlic family. pomegranate berries, green tea to a certain extent, herbs and spices, particularly turmeric. And many, if not all of the above, also activate Nrf2, which is of course, as we know, a key activator of antioxidant and anti-inflammatory pathways. Here's just an example of the information that you might find in the IFM Detox Guide that's targeted specific pathways. So again, have a really good look and read, print it out. and use it in clinical practice. So an important practice point I'd like you to think about is always target the food environment first and that's really really important to clean up and sort before you go anywhere further. There may be a role for supporting liver function during treatment supplementally for example with silymarin or some of the other interventions providing there is no interaction with therapy. Please do not embark on any big detox programs that aim to mobilize toxic load during active treatment. The body is already under huge physiological stress from chemotherapy or radiotherapy. And please don't try and do big detox programs if you haven't ensured a healthy GI function, because you need to have treated dysbiosis and increased intestinal permeability before you start to work on anything that mobilizes toxic load. Otherwise, you're just pouring fuel on the fire or recycling your toxins around. And this does include dental work and it's important because our clients sometimes might not think about doing something like amalgam removal during treatment and it's really important that we don't do that. We don't want to add to the load, we want to be able to complete the phase of treatment, clean up after it and then if we need to go into the stage three, which is the renew bed, then we do it in a targeted support. and careful manner. This is really, really important. We're not wanting to overwhelm the body and overwhelm the metabolism with trying to mobilize everything all at once. Of course, we know that there are things that work on us on a gentle level that will really help us on a day-to-day basis, and that's ensuring good hydration with clean filtered water, supporting gut health, ensuring daily bowel movements, sweating through Physical activity, ideally outdoors and clean air. And using infrared sauna very low and slow is likely to be appropriate in most cases. And you need to adjust it to tolerance and review clinically. If someone can't tolerate it, then just don't use it. Or use it at a different point in your therapy support plan. But for most people, low and slow infrared sauna does work and is supportive to their system. You are not aiming to provide high dose of glutathione pathway, supplemental antioxidants, such as giving people liposome of glutathione or NAC during active cancer. That is not appropriate because it can actually protect the cancer cells and interfere with the treatment. So you are not aiming to do that. You're aiming to do good nutritional support. If there is a bit of supplementation that's necessary for supporting liver function in terms of hepatic toxicity, and it doesn't interfere with therapy you can do that but certainly no high dose glutathione and max implementation during an active cancer process that's not something that we want to do so in summary our key goals within this particular system are to reduce toxic load and manage the exposome to promote normal balanced detoxification processes as appropriate to clinical situation cancer type and without interfering with medications And in our assessment, we want to assess environmental exposure at intake using a questionnaire or your interview style. We might be wanting to look at SNP panels for hepatic phase 1 and phase 2 detoxification pathways, relevant, and potentially testing specifically for whatever we think the trouble might be in the clinical context, like organic pollutants, including glyphosate, heavy metals, mycotoxins, whatever we think. is lighting up to us on our history. And from the support programme we are looking at our 6Rs, so the stage 1 is remove, reduce, replace, stage 2 is repension, rebalance, and stage 3 is renew only if necessary and only after active treatment has been completed. And it's important for us to, as I said, split those particular strategies into exposure management, which is why I always do the first bit first, because we need to turn off the tap from the toxic load perspective, not just mop up downstream. And then we do replenish and rebalance. And that's modulation of the relevant phase one, phase two pathways, making sure someone is adequately nourished to be able to detoxify properly. Using the clinical context in the SNPs to do some targeted support, and that's using the IFM detox guide to look at that. And of course looking at hydration with clean water, sweating and daily bowel movements to make sure people are using their normal healthy elimination processes to help themselves. Thank you very much. ________________ 3.7 Month 3 Live Meeting All right, hello and welcome to the March Q&A. How are we getting on with the course? Okay, thank you. Sorry, Melody, you wanted to say something. Okay, I'm just waiting with bated breath to find out about the case study now. You are preparing yourself mentally already, okay. I like it. Is there anything like my dissertation for my master's? I think I'm going to have to take a lot of ashwagandha. Yes, but this will be much easier. This is a clinical case. I'm not expecting a book here, okay? But it's just, yeah, there's just some important things to think about. But what I would do is don't be tempted. You'll get the case on the 1st of April, basically. Please don't be tempted to start working until you finish the lectures. Please don't, honestly, because you will get down rabbit holes. You do have to try and finish the material before you start on it because the idea is you expect to draw on all of the knowledge base to be able to do the assignment. So please try and get through the lectures first and then look at the case. It's good to look at the brief just so you know what you expect to deliver. but just don't start going through the paperwork and formulating your thoughts because you still got 50 of the systems approach to go in april so there's still quite a lot of the stuff to cover and so yeah don't be tempted to jump straight into it um however tempting it is to look but um i think understand the format and the only other thing to say is just bring as many questions as you can to the next q a as well so even before you start working on it maybe just bring some other procedural questions is there anything in the brief that's unclear so We're not going to be taking questions in the group from that perspective. So I do want to discuss it in the Q&A because it's much easier for me to show you and have a proper conversation about it. So you can ask questions about the assignment in a normal kind of once a month post. I'm not going to be taking individual questions in the group because that's. That's a recipe for missing stuff and it's a nightmare. So there's an opportunity to ask questions in the Q&A or under the one post per month bit where you all put down your normal questions from that perspective. So just use those times and you'll have one Q&A in April and another Q&A in May before you submit as well. So you've got at least two Q&As before. you have to submit the assignments. So use them wisely because it's really important. I'm not going to give you any answers, unsurprisingly, but I will be able to clarify things. So if there's something you don't know how to tackle, then I'm really happy to do it, but you will not get an answer out of me because the whole point is for you to give me the answer. And what's the deadline for it? Let me just check on my system. I will tell you what it says. I can't keep hold of that in my head at the moment, especially organising SAO Europe at the moment. Oh, that's true. that's not to do with the conference is out of my head at the moment so let me just quickly check on when your deadline is for this year because it slightly changes every year the date because of the calendar so let me just quickly check for you Has anybody else got it in front of them while I'm trying to log in? Don't have a look. I think if it is not cooperating at the moment with me, let me have a think. I will find it. It's just not sending me the code at the moment to log in. So just bear with me and I will give the answer to you by the end of this call because I'll have the code. If not, if you're not sure, just ask. Emma or I'll post it on the group. Okay, thanks. But it is all in there. So you would see it in several places. It would have been in the first pre-module, if that makes sense. Yeah, I did see it. It is somewhere in there, but it just might not be easily available. 25th of June says, there we go. You've got lots of time. So that is important. The key thing as well, just from the extension perspective, it is an academic extension. So only... academic reasons if that makes sense it would be acceptable to university are acceptable by n-tech as a reason for extension so you can't really write to me two days beforehand saying sorry i haven't organized myself to submit my assignment on time because there are some specific rules that i have to submit to n-tech and get approval for so there is a full procedure for how to request extensions right don't do it two days before please because you're quite unlikely to get one unless you're keeping in hospital or qpl or whatever else something really major has happened So you do need to submit it and it needs to be submitted with evidence like you would for any university extension. Right. That's it's the same rules because it's a level seven and accredited course. So it is indeed so. Right. And let me just quickly share my screen. for your questions and then we'll start looking at that. So the first question is if vaping is considered a risk post-surgery like smoking? So we will answer this question together because I would like to know how you would go about answering that question yourself. So I can't really see the questions. It's very small, not sure if that's just me. Can everybody else see? Yeah, maybe it's just me, then the way I've got it, okay. So how would you say, for example, a question like this, if you were in practice and you didn't know, how would you go about answering it? What would you do? Anybody, shout out. Google. Good. Google. Not Google, PubMed. PubMed, yeah. PubMed, okay. So what am I... I would have said yes because it's got, I mean, it must have lots of chemicals. No, no, but that's not the point. The point is we're doing now... now is we're going to answer that question together so that people who are less familiar to searching and how to answer the question themselves understand how to search for it. So what am I putting in the pub here? Vaping and pregnancy and in capsules. And what? What am I putting in the pub? pregnancy no that's vaping and surgery because it's a surgical question so is vaping a breast post surgery like smoking yes so I could have thought it was pregnancy then yeah so surgery so as an example again OK, yes, it's linked to lung cancer risk. Fine. So that's just talking about I'm just going to do a random one here. But you can continue going through it. So you can see for this is the teens admitted for orthopedic surgery. Can you see this bit? So combustible cigarettes are basically your main thing because it will have obviously the cannabis separate, but nicotine and nicotine derivatives, of course, in e-cigarettes. And. and depending on the vape component so you can say it represents a perioperative risk for induction, anaesthesia, post-op pain and analgesia requirement, issues with delayed wound and fracture healing. I mean obviously within this particular it's quite a nice review actually this one it's got quite a lot around what the different exposures and carcinogens might be as well as other bits and pieces it's quite a nice I would say from the from the cancer perspective it's actually quite a nice review to look at um this 2023 review so we can answer that question right so we can say okay well i mean i can go through it and see if i can find some evidence for um cancer surgery in particular but we can say the likelihood is that it will increase risk of post-operative complications and therefore we probably need to be managing that proactively anyway so i don't think it's a major surprise to hopefully anybody in the group is it In terms of endometrial cancer risk with tamoxifen, it's increased between two to seven fold, depending on the study that you read, compared to the general population. Usually five years plus of tamoxifen use is about four fold increase in risk above baseline for an endometrial cancer. And so any breakthrough, any weird bleeding patterns, any changes in bleeding patterns and tamoxifen required. as a pretty immediate referral for pelvic ultrasound and follow-up from the gynecology perspective. And then in terms of what we can do specifically to support it, so I mean, I tend to have a pelvic ultrasound for most of my patients on hemoxifen annually anyway, so I can monitor the endometrial thickness to make sure it's not significantly increasing, because before we get to hyperplasia, so hyperplasia is, of course, increasing the tissue itself, and then you can do a lot of other things. Neoplasia is the cancer process, but endometrial first thickens then becomes cancerous effectively. So we would want to pick it up at the point where the thickness is increasing before it becomes an actual cancer. So medics will usually, again if they are integrative medics, they will normally follow up their patients with tamoxifen with either annual annual or every two year ultrasounds from the pelvic perspective to make sure that we've got normal endometrial thickness. And then we'll be asking women about their bleeding patterns as well to make sure that nothing weird and wonderful is going on. In terms of what you can do to support risk, there's not a lot of evidence out there. But from my perspective, clinically, what I find is in those of my patients who had increased endometrial thickness, where we've managed their normal oestrogen detoxification. So we've managed the elevated 4-hydroxy and 2-to-16 ratio. We've been able to normalize the endometrial thickness without having to worry about and without progressing to neoplasia. Now, again, do I have a trial to say that to you? No, I don't. This is just my clinical experience. I would aim to normalize oestrogen detoxification because the idea is... is that tamoxifen in quite a lot of big proportion of patients because of lack of negative feedback on the hypothalamic pituitary ovarian axis, that blockade by tamoxifen will basically prevent that feedback from happening normally in a good proportion of patients. And therefore, the actual serum estradiol will be quite high. So that's what really drives, because it's not blocked in the endometrial tissue, that can dry endometrial proliferation because it's not countered by anything. So to... make sure that we are managing that we'd want to try and bring these to dial levels as much as possible within the normal setting and manage detoxification. So I might be looking at if somebody's really hiking up the ispidyle, I might be looking at are they excessively aromatizing, and I might be managing that. as well as making sure that both phase one and phase two is done as optimally as possible and we're getting enough protective methoxy metabolites not so much certainly of the full hydroxy in particular so again that's clinical experience i would love to run a trial on that that would be actually really amazing nobody's funded that yet um so immunocom for cancer patients ever you hear somewhere I think we've actually answered that question the first time, thank you. Good stuff, that's all done. And then Becky was talking about the oral microbiome and then the forefog theory, she's always had to keep on top of the mouth hygiene. um coated tongue tell me about coated tongue vick and go well i've my experience was that i felt like at one point that the chemotherapy was coming out every which way of me you know like i just felt like toxic and my mouth felt because I can feel tingling and my tongue would be white and quite rightly the hospital said it might be oral lichen but I didn't feel like it was I like I looked up very very carefully and I thought I'm not sure it is so I was using like like tongue scraping oil pulling like and I would sometimes use charcoal and spit it out and anytime I saw the white I'd try and get it off even I had to do it several times a day just to keep my mouth as I needed it to be because I was really really worried about it and it was it just felt like such a procedure because I just had to be thick and white um and um and I did I successfully did it but I was like is this how going to happen with other chemotherapy so this is very specific you know to my my personal experience different people will respond differently realistically and I would say that you know the main complication wouldn't be actually oral lichen I'd be worried about in your case Becky I would be worried about oral thrush more Because that's what... chemotherapy is definitely a recipe for increased risk of all thrush. So that's something that's an amazing amount of nurses don't look in the mouth of their chemo patients. And then they go, Oh, I've got a sore mouth. And I've got, you know, I'm really having trouble eating properly. And I'm like, have you looked in the patient's mouth? Is it just ulcers? Or is there ulcers and candida there, which is we need to treat that. So I would say that most chemotherapy will have risk of mucositis and therefore will have risk of like I said, that quite sensitive mouth, you might get thing that we might just get ulceration, you might just get bleeding gums and the other thing complications that might be complicating that. Some people do get thick coating you know the yellow thick, sorry white thick coating, some people will get other types. Oral hygiene of all kinds is just essential in chemotherapy. So soft brush toothbrushes, nothing hard, natural toothpaste with no SLS, really important that really really makes a big big difference. oil pulling is fine, coconut oil pulling is used by a number of our patients. If people do get mouth ulcers, then there are some specific ways of managing that naturally, as well as some of the counter stuff that we use. But yeah, oral hygiene is really important. You will see either tongue or oral complications of chemo in a lot of cases not just for foxiri and but many many different chemotherapies and just keeping on top of it is really important okay so thank you for hearing your experience very important um coloscopy bowel prep i would just caution that if it's obviously prescribed to your patient obviously it's a prescription only medicine so technically speaking without checking with the doctor you wouldn't be able to use my protocol because guess what it is a prescription only medicine but it's the one that we use in clinic because i'm a allowed to mess with. Oh I see, that's very helpful to know. Yeah, just because unfortunately most PrEP is prescribed and therefore because it's considered a POM you guys will probably not be able to use it unless like I said it's under supervision of a doctor you checked with somebody and said that's fine. I have to say though that using this protocol we've so far had zero percent of inadequate PrEP. Whereas actually using conventional hospital bowel prep, we've had a number of patients not have adequate prep for a colonoscopy, but it is what it is. And yes, you're right. So colonoscopy is because. They're only going in a sigmoid colon. You don't have to have such a big clear out ultimately. So usually an enema is fine. And there's different ways, there's different enemas around from that perspective. So it's about sometimes patient talk to their team and say, can I have the least invasive? there's little mini enemas that might be enough especially if they're having a good amount of fasting going on beforehand to make sure we're not putting more in the sigmoid colon but um yeah that's it is definitely a different prep to a full colonoscopy where you have to go around the whole colon to be able to see everything it was interesting in my hospital i could see that there was um a change in approach because i had this situation where my surgeon was quite frustrated at one point because the um the pre-op gave me the bowel prep and then he was like what do they do give you a bowel prep i want you to have an enema because i think it's going to be worst outcomes if you have a bowel prep you know he sort of explained it to me um quite frustrated because he said no no our way is use an enema in that area because you know we don't want to have the least disruption I thought that's super interesting that you've got different almost different procedures in the hospital yeah absolutely and I think you will find that it's just what what they you probably find is that the normal kind of average theatre staff just want to have the least amount of recalls of people who are inadequate prep so they will take to over prep patients and then obviously the surgeons are aware of the fact that it's really not a great idea to clear people out unless you really need to frankly and for full colonoscopy they will do that because sometimes that's exactly what you need but For a sigmoidoscopy, it should be a really easy prep and it should not disrupt a significant amount of the microbiome. Tocotrienols and palm oil, you'd have to have quite a lot of palm oil to get 125 milligrams of delta and gamma tocotrienols. So I would have a look at that and see how much they're actually getting you and think about. How much of the amount of palm oil is going to impact the rest of your fats? In terms of the membrane fat composition, I've been really cautious with that. So to be honest, to get 125 milligrams of delta and gamma specifically, I think you'd have to go some on the... consumption of farm oil. I don't remember the exact percentage but usually it's quite a low percentage which is why they're concentrated down. Right. So I have to say I don't tend to do it that way and skin absorption there's no studies transdermally how you're going to to get that in and then be able to absorb it into the serum at the level that an oral 125 might be able to give you so 125 milligrams is my minimal dose for delta and gamma-tepratrenols in general so to do that again how much would you have to really apply in the skin is a question i've never seen the study so it's really tricky to kind of answer that sensibly because i don't think anybody's actually run a trial of what it would take to get the target amount and Thank you very much. And then Gabrielle, I think all of us, we might not have access to this. So it's obviously behind a paywall. So I don't think we'll be able to get a paper for that. So I sometimes can get access to papers to various bits and pieces, but I think this one's behind a severe paywall. I think I was just curious about the strains because they just mentioned the species in all these studies and there are lots of different strains that do different things and it's just meaningless. Yeah, exactly. Well, the worst one is, do you know that the, looking at this, is that the strains they use, because I know I analysed that paper. In fact, I might actually have it, because I analysed this paper for, what was it? There was another, I think they did some anxiety and depression outcomes. So I did it for the anxiety and depression guidelines for SAO-ASCO. I think I analysed a subset of that data. So remember it. And none of the strains they used were psychobiotic strains. So they were trying to measure impacts on, you know, psychological outcomes, not you. using psychobiotic strains, which was really bizarre, I think. So I'll see if I can find it. If it was part of the paper analysis for the trial, I will be able to find it. But usually, yes, they have to put it down. I bet they haven't mentioned it, because they usually would put that in the abstract. So, you know, okay. Which is not very useful. And you will see, you will find that most probiotic trials done by people who don't know about probiotics, unfortunately, are rather useless. Yeah, I know. I'm with you. I find the same with herbal medicine. Like, I love it when they try and do an inappropriate... herb, an inappropriate population, inappropriate dosing, appropriate amount of time, and then conclude it doesn't work. I'm like, yeah, that was a really useful trial. Yeah, so using non-psychobiotic strains and psychobiotic type of research is ultimately useless. You know, you don't use IBS strains to try and do something else, you know, to target the, I don't know, gut-bone axis or whatever you want to do. It's very odd. Elagic acid and unknown amurocardin, no. I tell you what, I tend to... to just use a reasonably simple stuff around it. So I don't ever have to go to that. But if you have experience in that, it'd be nice to hear, Helen, if you are here somewhere. I know I haven't. I just remember reading about it when when the HPV vaccines were coming out. And I just sort of went back to my old notes because it sort of rang a bell when I was reading the notes. So I just wondered whether you had experience of it or not. No, we tend to use the medicinal mushrooms as a part of it. Let me just quickly find my little, I should be able to find one thing about, see if I can find my little, I had a little slide on it that I presented as a part of something else. And I'll see if I can find it. There's my little easy bit. What happened there? One moment. So let me just see if I can find my little slide. On the HPV prevention. Oh gosh, now that's translating to Azerbaijani. That is not the point. Let me find if I can actually... Oh, yeah, we got that. That's better. So that's... We kind of just use this as our main approach from the HPV as a persistence. So unsurprisingly, food first, right, from that perspective, making sure they've got enough carotenoid intake, making sure they've got enough folate intake and supplementing if it's low, selenium, AHCC, and... papillomelanin care. So that's kind of what we tend to use most of the time. So yeah, that's, and to be honest, I've never had a persistent problem that I couldn't solve with these sorts of interventions, usually. So usually they will respond. I occasionally might give, just in a broader setting, if we're looking at what might be the other factors contributing. to HPV persistence. I would sometimes correct other things as a part of that, just depending on what's contributing to the immune dysfunction of why you're not clearing from the viral perspective. But usually, you know, simple interventions do very, very well. You just need to give them enough time to work. So usually you need to give them three to six months and then repeat the HPV triage to make sure that they then cleared it from that perspective. But yeah, as I said, I've never had a problem with not clearing it. Obviously, I've had people who presented me way, way later after they were developed the cervical cancer post high risk HPV. But generally we can clear high risk HPV with no problems. in very rare cases we might have to use things like nistotra to try and activate the immune response but again it's just like once in a blue moon probably. The amine is an amino acid so I tend to find that it It's absorbed better, frankly, away from food. It competes less than other amino acids for absorption. It can actually improve absorption from some of the other amino acids, but I tend to give it away from food from the absorption perspective. I don't think I've ever seen it, giving it with food, having an evening out effect of it through the day. But if there's any pharmacokinetic studies that you've seen on that, then I'm more than happy to take a look at that. Toothpaste brands, gosh, it's so individual. You know, people like so many different things. Let's have a little poll of toothpaste brands just for a laugh. Come on. Go. Shout out. What have you got at home? Dr. Bronner one. Okay. I use the bar side one at the moment. Yeah, I'm using the bar side one at the moment. I use dimples as I think one of the ones that I use. Anything other ones that you use go? I feel like I'm being ripped off with the gutology while I paid a lot of money for it. I'm not going to get the money down. Kingfisher. Yeah, Kingfisher's another one. I alternate between Kingfisher and the one that's got silver and probiotics in it. But the thing I don't understand understand is why does the silver not kill the probiotics yeah i mean i'm not i'm not so sure anybody's actually run a study on that particular toothpaste um aloe dent is another one that's quite popular with people so that's another one to use you know i tend to just give people lots of choices because you know it's everybody's so individual some people love certain flavors some people hate certain flavors and i've long given up trying to figure out which flavors people like so just give people about five or six choices and get them to experiment with it themselves so So in terms of mouthwash, I find the Saracen is really gentle, but really effective, especially if there's sensitivity. And it's from the African toothbrush plant, you know, where. Yeah. We use the twigs to brush their teeth, so it's from that and I've never found anybody react to that. It's very soothing. It's a similar one, Ayurveda as well, there's certain herbs that are used as toothbrushes effectively, so it's definitely quite a common thing, so that's great. And I think that's, I would say, just give people choices, just because you don't want to have like one or two favourites. and then you find that people go, oh, that one tastes horrible. So it's a bit like when I give people herbal medicine and they're like, that doesn't taste great. I'm like, yeah, it's called herbal medicine, not herbal sweets. It's going to be tasting like medicine. Sorry. make it as palatable as possible, but it's still going to be medicine. Good. Colosan Mago 7 is probably the closest one now to that. Honestly, ignore all of the oxygenation rubbish they say about the product. It's just good old magnesium oxide and that's why it's good for cleaning the bowel out. There's a lot of claims they make on this product, really. I'm not bothered by it. From that perspective, it's just good old magnesium oxide, which is an excellent laxative. Since you really good for people even for example when people get the constipation post um post chemotherapy with ondansetron or granicitron with all of those 5-ht3 drugs it's also a good one to give because if you give powder they people can titrate it up and down themselves a little bit to make sure they get bowel regularity uh but yeah MAG07 I think is the new name for it effectively So CRP doesn't need to be in the lab within eight hours actually. It's the ESR and LDH that do. And usually, yes, LDH is actually probably based on probably, well yeah, LDH is definitely six hours usually. So you can't actually, do you know what ESR actually is? Because it's asked about centrifuging a sample. What is ESR? How is it measured? Does anybody know? I'm now feeling the sedimentation rate. The rate at which the cells drop and it's in a specific test tube, is it the Walgreen test tube? Yeah, yeah, yeah, exactly, exactly. It's like a controlled environment. Exactly. So can you centrifuge before you do this test? Probably not. No. No. You need to have the actual normal two mil of venous blood to put into that test. You can't pack red cells before you then decide to let them drop. Like, you have to actually. That doesn't work, basically. So ESR, you can't. If you measure it by that method, they are developing other methods. So there is a centrifugation method. I've not seen labs used in the UK. But you generally don't find that that's. They just make it not available, for example, from that perspective. They can't get. get it done. LDH. There's just, it's a biochemistry sample, so centrifuging it, not centrifuging it doesn't actually affect it. You just need to get it in. It's unstable. Yeah, it's just unstable. So you have to just get it in. It's the same thing as if you're trying to measure coagulation, coagulation factors will not stay. No matter how much you centrifuge them, it won't actually be accurate. So unfortunately, you do need to have a patient have access to blood. I mean, from our perspective, like Randox. has access to ESR and total LDH, not LDH isoenzymes, but they are quite good to use and they have reasonable access from that perspective. So most Randox locations will be able to transfer to lab within a reasonable amount. of time. Obviously in London you have TDL, you have other London labs are pretty easy, it's usually when you have to go to Scotland or Wales somewhere then it becomes a bit tricky. But I would say that we can't, centrifuge unfortunately doesn't solve solve that problem. That's definitely an interesting one. And you don't need them all the time as well. Don't forget it. You kind of need them when you want, when your plan will change. So you only order a test if you can change your plan based on the results of it. You know, if your CRP is 40, do you really need somebody's ESR? No. No, because guess what you're going to be doing? You're going to be managing the inflammation and then the ESR may or may not be elevated at that point but you're still going to be managing that inflammation. Now the other way around doesn't quite work so CRP can be normal, ESR can be significantly elevated so if you are still thinking you know what I've tested up and down from the inflammatory perspective they still have, I think they have high inflammation but I don't have any ESR on them. I would want to test that, that's fine. But you might do it as a one-off if it's normal, you're not going to continue testing it necessarily unless something clinically changes in the person. So use those tests wisely because they're a bit of a pain to organise from that perspective. Dysbiosis, yeah, this was a question about treating dysbiosis before looking at anti-inflammatory support. Sometimes I do do them together, it's fine. But I just always think we need to make sure that we don't just treat symptoms, we're looking at root causes all the time. And the herbal antimicrobials are really interesting. So from my perspective, any antimicrobials will almost depend on what the gut environment is like. Like it depends on what I get back on my test and what the symptoms are and what my priorities are and how strong the patient is. There's no, you know, I think Melody Yorn you want to have a relaxed force, right? Yes, yeah. Yeah, exactly. So, you know, so... And what antimicrobial and what it's used for. Exactly. And the thing is, there's definitely a role for them. We've spoken from... from overusing them to kind of, oh my goodness, we shouldn't be using any antimicrobials. And like the answer is somewhere in the middle as usual, right? From that perspective. Yeah. And he's like, he obviously does his own tinctures, which are completely different to some of the products we have access to. Yeah, exactly. And again, I'm probably slightly weird there because I'm herbalist. I will do my own pictures too, but it's, I also have access to DCM herbal granules, which can also modify the gut microbiome in very different ways to the traditional kind of products. Do I use herbal antimicrobials? Yes, I do. and I will use them a lot more probably in my cancer population than I will use in some other populations because I also need to protect people with vulnerable immune systems so I will proactively give things like andrographis to people at high risk of respiratory infections if they're traveling and they're going to be exposed to all sorts of funky bugs because what I do not want is them landing in hospital on the other side of their travel from that trip perspective so I will give herbal antimicrobials for multiple different reasons but it's about doing you can rush rational way of saying, what are you targeting exactly? And then how do you rebalance the whole microbiome ecology around this rather than going, I'm just going to blast everything and see what happens. But equally, there are times when you need to be able to remove whatever it is that you're removing. You know, if I've got patients with SIBO and they have diarrhea five to six times a day, I will refaximin them. And I will do other things from that perspective, because guess what, I'm not leaving them to be depleted, because it is not appropriate if somebody is losing weight or is not able to eat properly. or is malabsorbing because they're already at high risk they already have cancer for goodness sake so i will use whatever is available at my disposal whether it's herbs or medications or anything else from that perspective but it's just about finding the right rationale the right duration and the right overall ecology approach around it so that we're not stuck on saying it's a yes or a no it's always shades of gray and it's always what's appropriate based on the data in front of you whether it's the breast test the stool test whatever it is in a clinical full clinical picture unsurprisingly as well so that's kind of my approach to it and I don't know how other people feel about it. I have a question which I didn't put in the group thing because I was thinking about one of the modules and about viruses causing you know some some cancers so what do you do if someone comes in they already have cancer but you know that the virus may have caused it plus other things do you go immediately to to try and get rid of the or support the immune system so they can get rid of the the virus at the same time as doing the cancer therapy or does it completely depend like everything on the individual more cancer what stage etc etc and what virus yeah yeah my perspective i think that ultimately i'll be doing immune support anyway of what of whatever kind it's just about targeting it to the situation you're right it's if the answer is it depends if there is a viral driver whenever possible we'll try and keep it under control or if it's not clearable because as we know they're persistent viruses that are not actually clearable they're controllable but not clearable from the body once they become persistent um and whatever we can clear we should be clearing on that side so but it's about looking at it of saying okay well you're going to have a depleting immune system anyway if you're going in for chemotherapy or radiotherapy is your thing the other side is don't forget we then have patients who might be have a originally previously viral to and cancer now they're getting immunotherapy and that's a very different immune environment now we've taken the breaks of that immune system and is going after everything so may or may not clear the virus but it's a very different management approach to somebody who's got low neutrals on chemo so it is very much depending on what treatment what virus what stage how well the patient is what other challenges they might have and what treatment they're on Could I ask about biofilm disruptors? Are they kind of middle ground? Are they considered as an alternative to antimicrobials? They don't do the same thing. That's the thing. So biofilm disruptors, all they do is make your... material biofilm were accessible to antimicrobials. They don't actually have any antimicrobial effect in themselves. So they are used. So I use seropeptase the vast majority of the time. So I don't use NAC for many reasons. I use seropeptase. I can use rosemary sometimes. There's other herbal medicines that can be biofilm disruptors. But just disrupting biofilm doesn't get rid of what's sitting in that. You do actually need an egg. form of antimicrobial, it might be very gentle dietary antimicrobial, this might be a Rosemary oregano, you know, that might be the daily RTO, would be your route to doing that, but you do biopharm disruption by itself doesn't do it very much from that perspective. If you actually don't clear whatever's been sitting there from the LPS load, people get more symptomatic, not necessarily less symptomatic. I don't know if any of you found it, but if you just give pure biopharm disruptors, people don't get better. Daisy is not able to say she's had an experience. I work with a lot of Lyme disease clients and you have to wait because it can unleash stuff but having said that if somebody comes to me with urinary tract infections and they've done multiple tests with their GP and they haven't found anything I'll stick them on biofilms before I'll run a urinary tract test and that's very helpful stuff comes out. Yeah, I think what I tend to do is just try to avoid mobilising things without treating it. Like that's just generally, certainly within the cancer population, you do have to be particularly careful about it because their mucosal immunity is so compromised. You're not working here with people with normal immunity. systems vast majority of the time so because you're going to have increased intestine permeability because of chemo steroids all of the other wonderful things you get put on from that perspective you're going to have a compromised mold because you don't have a normal immune function you just have to be so much more careful with those patients and clients and you would with your normal population and so I would say treat with caution. I feel quite strongly about this area especially in the sort of digestive cancers because you know again I'm informed by my own experience but when I worked with Linda you know our prehab of my gut before chemotherapy I think was instrumental you know I had F-nucleatum in my gut and so we had rosemary we had black seed oil but also I was packing like packs of herbs into the NutriBullet. it with garlic with lemon with oil whizzing it up and i would have it on my lunch and i didn't like so you'd have like one pack of herbs will go down to a very small amount so you can have a really intense amount with fresh herbs by doing this like a flavor bomb which is so amazing when you can't taste anything so you know i think these sorts of things are really a massive important because my belief is that it affects treatment outcomes you know because if i'm sat with f-nucleotide in my gut the research says i probably would have had not such a great outcome So maybe, maybe not, who knows? But, you know, that's one of our sort of targeted approaches. Absolutely. And we know it affects treatment outcomes. And we also know that's why that whenever we can do food first, because it's the appropriate thing to do, we should do food first, full stop, and we should reserve any of the heavier interventions for when we do it. But equally, you know, had a patient in clinic who had mid-acetic breast cancer on Abraxane, so she's had some radiation to the spine actually because of bone mets. She got a significant oesophagitis as a problem with that. Again that was poorly treated so I ended up treating that. And then because of course all of that disrupts oral intake. Then she got significant GI symptoms. starting with diarrhea. So she had both. She did have some radiation to the spine lower down as well. So that didn't settle. So radiation kind of enteritis, which is what we can get with spinal radiation, didn't actually settle. She's got celiac. the SIBO likelihood is quite high anyway. So in this case, I'm not going to sit around and wait for her to become further depleted because she's already had a week or two of poor oral intake because of esophagitis and radiotherapy. I'm going to be treating that, and unsurprisingly, her symptoms are improving now because she is on a vaccine, and she's properly treating her gastro is agreed with our management. But it's just one of those things whereby there's certain situations where you should be going as, most of the time you should be going as gently as possible, but there's times when people will start plummeting off the cliff as a medic. my bet is to pick them up, get them back on track, and then figure out the rest of it. Of course, that's not going to be my whole microbiome management, I'm surprised. We sent off a store to us, and we're going to have a look at hermetic explore and optimize the full system. And as much as it can be optimized, given the fact that the continuum of braxane is going to be dragging us down anyway, and there's going to be limitation with patients, certainly of what you're going to be able to do while they're on ongoing chemo and steroids and all sorts of, and PPIs to cover the steroids. So let's not forget that bit. A lot of the time when they're on a high level, they're going to be on a high level. higher dose of steroids that will get all of the lovely PPIs, which is important because So, we're going to get gastritis apogee bleeding potentially, but equally that's going to be a further microbiome disruptor. So, you kind of... microbiome is a complex thing sometimes you have to accept that you are handicapped in a significant way until this course of treatment is completed and you do as much as you humanly can you know through diet and other safe interventions and then you wait until they finish that course of treatment and then you work a lot harder on optimizing what's there but very important multiple outcomes i think have any of you went did any of you go to my iowg talk on immune checkpoint inhibitors anyway um so that was a very interesting Do we talk about my ovarian cancer patient and immunotherapy in the gut? No? Okay, good guess. That's a little bit of a fun case. Although, shall I reserve it for you for the case study? Ooh, maybe I should. Yes, I think I will. There we go. Sorry. Sorry, I'm not going to tell you this case until later, and then I'll tell you how it comes in the end, which are really good, actually. But this was a patient. All I will say to you is that the… I may give you another case. Anyway, what I'll say is that patients that do immunotherapy, there's a number of patients that we've had on immunotherapies where looking at the gut microbiome and modifying some of the other modifiable factors has created a response that's unheard of. in that cancer with immune therapy. So what Becky is saying in the clearing of fused bacterium nucleotides is actually very, very important. From a risk factor for young colorectal cancer, it's a really major colorectal cancer risk. So it absolutely makes a... massive difference to the outcomes. And you can convert somebody from being, you know, having probably a very low risk or low chance of responding to immunotherapy to being a good responder. That's where we have the power. Because a lot of the time, the oncology guys will not have a clue how to reclassify people's risks in that perspective. You guys know how to assess that and reclassify it. Because my interest in biomarkers for all of this really lies in, we're kind of in medicine. got it to a point where we go biomarker okay great well it tells us about something about the prognosis or something about how they can respond to treatment and i'm like that's lovely now you tell me how you're going to modify the biomarker to reclassify the patient into a better prognosis category or a better treatment response category and everybody goes i'm like well that's the point right the point isn't to try and predict the response and then go sit on my hands and go for you you're in a poor response category is going what the heck do i do to try and improve your response so that's That's really the active area of research in interpretive oncology. I'd like to see more of that coming through. You're saying, for example, if we can optimize somebody's inflammatory status, what can we do to change the outcome, right? So instead of just running all these association studies, which there are millions, maybe not millions, but definitely thousands of cases saying high-elevated systemic inflammation leads to poor outcomes in cancer across multiple cancer types. And congratulations, many, many studies will show that. Yeah. what about the other way around? What about if we correct it? What impact does that have? Has anybody run that trial? Not as far as I'm aware. So that's what I want to see more of because I want those intervention trials that are biomarker directed because that's how we convert certainly from a medical perspective, the medical profession. Anyway, right, I'll move on. Andrea is asking about astragalus. So yeah, astragalus is an interesting one. So I'll give you two perspectives. Astragalus does have have an immunomodulatory role with an immunostimulatory lean. So you do want to be careful with that in patients with autoimmune disease. Okay, so that's a caution, not a contraindication. An experienced herbalist can use astragalus, I've done that myself, to get actually better control of autoimmune disease if it's correctly couched in correct herbs otherwise, okay. But certainly high dose of astragalus in people with active autoimmune disease flare is not something I would recommend or advise. In TCM, we do not use the stragglers in the acute phase of infection. We actually stop it. So it's as good as an immune protectant up until we get that infection. But actually, because the TCM thinking is that in the very acute phases, you do not want to amplify the immune response. They call it something different, but that's effective. Usually during acute infection, somebody would stop a stragglers from the TCM perspective for the first three to five days. and restart it afterwards. So I would say, from my side of things, any time you've got more of an immune overactivation risk, you probably want to be slightly cautious with it, unless you're an experienced herbalist and you know what you're doing, in which case you know exactly what you should and shouldn't be doing. And the other time is, again, similar for immunotherapy. If you've got somebody going into immunotherapy, they've got inflammatory markers. Are you going to give them astragalus, do you think? Probably not, right? Because we're just about taking the breaks of the immune system. So it's possibly not the best idea to do that from that perspective. So those are the things I would say, if you're looking at uncontrolled inflammation or uncontrolled immune system response, would not be the time to use astragalus, which is probably makes sense based on this mechanism of action, right? If you read about it. Is that okay? Does that make sense? So Nina, would that include like leukemia as well? I'm guessing that would be... Good question. So a struggle with leukemia is an interesting one. I don't think anybody's done a really good trial, human trial on it. So there's some interesting preclinical data, which can conflict effectively. So I don't tend to use it. It's not my first thing to use in leukemia. Definitely not. I'm also really cautious of using other stimulants that particularly raise the IL-2, the proliferating factor. I can make sure. Yeah. So I tend to not I tend to not go for those things. I tend to look at the broader picture around leukemia and it's quite different to solid tumors. So with solid tumors outside of immunotherapy and really uncontrolled autoimmune disease, it's a little bit more common to use astragalus. Leukemias wouldn't be my first herb, basically. I would probably use other things. What would you consider to be a high dose of astragalus? Oh, well, good question. Are you asking me in capsules or are you asking me in... Powder. I mean, I'm thinking it's part of a general product that I use. It's got 200 milligrams. Yeah. Oh, gosh, no, that's not a high dose. No, good. What I would suggest is like, so for me, because I'm a TCM herbalist, so my dose of astragalus is a higher dose range is 18 grams, 30 grams. of decoction, that's my high dose. Now again, you've got a concentrate there, so you've got an extract, so of course that's not the same as having 200 milligrams of dried herb, for example, that's not the same thing. But still, you're not going to be reaching with your 200 milligrams of extract anywhere near the top doses that I would reach in TCM. So my average ginger and strawberry decoction is probably nine grams a day for patients. decoction obviously so don't forget you're not eating the herb you are extracting the astragalus polysaccharide and all of the water soluble compounds in it so usually we use a ginger and stragglers decoction and then we can double that quite safely without having any problems up to 18 grams and that's kind of that's um that thousands of years of experience so those sorts of doses are in traditional TCM pharmacopoeia type of things but again don't forget that's that's a not an extract it's an actual whole herb um 200 milligrams is fine it's an extract I wouldn't consider it high dose good you need to actually go way higher if you're going to have a good response so if you ever find that a straddle doesn't give you enough response the likelihood is you haven't given enough dose this is a product that I use from pure actually called epi integral that has a lot of different things in it actually. Datamine, I mean, obviously not for cancer, but just generally for gut support. It's actually quite useful. But okay, that's brilliant. Thank you. But I'm thinking you're using it more of a, I think using more of a source of maybe a stragglers polysaccharide, looking at kind of immune system modulation, but maybe looking at some of the other gut microbiome modulating effects. It's very different. Like when I use a stragglers within chemotherapy support, and... I am expecting it to have a reasonably strong immune supporting effect. I'm fighting these chemo, so I better be giving a good enough dose to be able to try and counteract that. So yeah, that's kind of how I tend to use a straggler from that perspective. But if you're never unsure, the other thing to say is like, you know, unless you're a herbalist or naturopath who's trained in herbs or whatever it is, if you feel uncomfortable, just refer. Just refer to your local NIMH, you know, Rachel said herbalist and neem herbalist, their medical herb. herbalist, they know what they're doing, or your local TCM herbalist. So ATCM will have a directory for it. Work with them. Say, okay, could you please let me know what you prescribe so I can have an idea? The only thing to, I guess, warn you about on the TCM herb side is that not all TCM herbalists are very good with interaction checks, because a lot of them were traditionally trained in China, where... This is not as much of an issue, frankly, because a lot of the TCM doctors who work in China are either integrated within the medical system and they have a pharmacist who understands all of that or they're double trained. So if you do use a TCM herbalist, you do need to keep hold of their herbs and you probably need to run a backup interaction check just to keep their mind safe. And that's my advice. Not that they don't know what they're doing. It's just a lot of them have not been trained to do interaction checks. That's just been my experience. you know Questions here. Do you prefer if we're using extractions, would you prefer glycerin based rather than alcohol based? Obviously, gentle on the liver detox. And also, do you have preferred brands and sources? Because I'm not sure about Astralogus specifically, but Other herbs like scope cap, they're very good at harvesting heavy metals from the soil and they're very often contaminated with heavy metals. I mean, unless you're, what I would say is, unless you're a herbalist, I'm not expecting you to prescribe herbs, right? So from that perspective, you need to be insured and have had enough training, certainly within cancer, please. Unless you actually have a really good practice within that, please do not prescribe. perhaps a patient with cancer unless you have that as a part of your scope of practice because you will at some point get a call from oncology or pharmacy and you need to be able to defend your baby as well and on my side i don't i use glycerides for different reasons too i i use everything if you look at my in fact i'll show you my little thing let me just dd blur myself and you can see what i've got in my cupboard next door let me just do a little d blurring Right, let's have a look at my little cupboard of goodness. There we go, so that's what's in my various bits of cupboards. So here are my tinctures for example, here's a small sample of our glycerides, although we'll have more around. We also have... capsules of various kinds and TCM herbs and granules. So, ta-da! This is my cupboard of goodies. So it doesn't really matter. I use what I think is best for the patient. what gives them the right therapeutic effect really. So there will be times when I will use a glyceride because somebody is really sensitive to alcohol or maybe it's had alcoholism in the past or whichever it is. But there will be times that a tincture is used because it has a specific effect to it. And obviously granules are mainly used within the TCM setting and dry powders are certainly used across multiple different herbal traditions. So use whatever you need to get the therapeutic effect. Thank you. Right, Adam. And Adam's questions are up next. Let's do that bit. Let's just do that. Yes, resveratrol. So that's quite interesting on the resveratrol side of things. So resveratrol is... That's actually lower oestrogen, number one. So all studies do not show that. That's really, really important. So actually, it's used as a buffer from the oestrogen perspective at moderate dosing in menopause. So we have basically a U-shaped effect where really high doses can actually push the oestrogen. And you'll see that in clinical studies. And that's because if you really, really push the resveratrol, because it is a 5-3 oestrogen, it will bind ER alpha receptors, not just ER beta receptors. OK. And it will have some of the stimulatory effects on it. And that's by using really high doses. So I don't avoid using it in ER plus breast cancer. I quite often will use moderate dose resveratrol or TP, transesterol, stilbene to manage the CYP1B1. But I will never push the dosing really high because I just don't know the safety. And because the studies in the clinical setting are really conflicting, you will say, oh, resveratrol has pro-hystrogenic effects. I'm like, well, it's probably because you've used a boatload of it. And if you look at the concept. concentrations if you used a really high concentration and another study will be like no resveratrol has an anti-estrogenic effect i'm like yeah because you used a moderate dose or a low dose for example so it's it's got biphasic effects and until we can figure out which high doses say i just won't go there for that reason does that make sense adam yeah sure so what what kind of moderate dose are we talking about then so 125 to 250 would probably be as high as i will go with resveratrol I probably stick with ER plus breast cancer, I would stick with 125. I use TP more frequently, so I usually use transesterosilbene, 50 to 100 milligrams. What was the reason? It's to help with CYP1? CYP1B1, yeah. So if you've got an elevated 4-hydroxy, it's really good, like both resveratrol and TP or transesterosilbene is a methylated version of resveratrol, basically. It's really useful in people who have a slow COMT and then hyperactive. CYP1B1 where you don't want to necessarily give them resveratrol because it could potentially slightly knock off the COMT because it's going to be using some of the COMT anyway to be able to methylate itself. So what I tend to use is for those combinations of a slow COMT plus hyperactive CYP1B1 I will use TP, Gero does one 50 milligrams and I would use one to two capsules and then monitor the Dutch to see what happens with the estrogen detoxification to make sure that they are 4 hydroxyls is normal. So yeah, that's kind of how I use it, but I don't go high. You will see protocols out there that use resveratrol at 500 to 1000 milligrams. Like I just don't feel comfortable using that in estrogen receptor positive breast transplants. Sure, makes sense. Another one was toxic exposure questionnaire. I just use the IFM one, really. That's the one I use, I'm afraid. But I think, have I given it to you anyway on the system? Yeah, so just use TEQ. I mean, I know it's on the system. Yeah. Yeah. yeah okay yeah so it should be in the detox resources somewhere but yeah just use that one it's at least it's been used by multiple none of them are perfect but i think it's quite broad and therefore it should give you a good idea of where people's exposures are um and then drug supplement herb interactions obviously you've got the natural medicines database and efficacy right these days now uh have anybody used efficacy recently what do you think i thought well at least it's quick Yeah, I mean, it's definitely quick. I really like it because, of course, you know what my major bugbear is, I'm sure for all of you is it saves patients drugs. Isn't it lovely? So it's nice because you can have the profiles for everybody. You don't need to input like some of our patients are on a boatload of medications and a lot of your cancer patients will be. So it's quite nice not to have to input five different medications and how many supplements they decided to take. Particularly people come to you having read. you know whatever it is how to starve cancer and maybe on 30 different bits and pieces so um yeah so i think these are the two ones that i use i've transitioned more to using efficacy for the reason of the ease of use it's still you can still interrogate all of the um um all of their papers behind it so whenever it shows an interaction or possibility of one always go back to the original date and see what they're saying and it's still got some of the optimizers it's not very good at depleting that's the only thing that i don't know if you found it But nutrient depletions, it's not as good as the natural medicines database. I don't know if you guys have found it, but it's not as obvious. When you put in the medications, you can find optimizers, but they don't always say like this depletes X, Y and Z nutrients. So I think that's probably missing things that hopefully they'll correct. But otherwise, that's the one that I would tend to use. The standard medical databases like BNF, I only use for medication checks. And same for Medscape, for example. So Medscape is great for doing drug-drug interactions, but drug supplement ones are terrible. So you're definitely going to pick a lot up there. So one of those is usually fine. And if you are an SAO... member, because if you're a band member you already have access to Efficacef and then they'll figure out what they're going to do with NatMed. And if some of you are not band members and your professional association doesn't give you access to Efficacef, then SAO membership does. So the Society for Interpreter Oncology membership will give you access to Efficacef and it's $99 for international members. for a year so it's pretty good value also from that perspective. Good and then Heather's asking about inflammatory markers which is really interesting so newer or emerging inflammatory markers beyond various things that are mentioned that show promise in predicting cancer prognosis response to treatment. So many is the answer but so but they're made up really of the same baseline biochemistry so SAI is one of them. for example, systemic immune inflammatory index. And that has a similar relationship. There's lung cancer, there's lipid lung cancer, prognostic index or something. There's Siri, which is again another one of the systemic inflammation indices. And the problem, when you look at what composes them, though, you will find that the same sorts of biochemistry things that we talked about. It's neutrophils, maybe lymphocytes, maybe platelets, it may be albumin and other bits and pieces. So being based on biochemistry doesn't actually change, it's how we put it together in the different indices themselves that's the important bit here. So I would say in terms of inflammatory biomarkers, they're not necessarily changing what we analyze, but they're changing the way we synthesize it in the different indices to show relationships. But SII has probably got the best research, I would say, out of the ones that are being used at the moment, and that's across pan can. I would say. So do you look yourself, do you look at those more traditional markers or are you looking at others as well? So I will look at all of those. And if I'm really concerned, I will run an SAI or one of the other. It's bound to obvious, you know. From that perspective, if I look at the individual markers really well, the indices composed of those are not going to give me any surprises. It's very unusual that I would get a surprise out of it. You know, if I've got somebody who's got thrombocytosis and elevated ferritin, do you think I need an SII to tell me that they're inflamed? No, I can tell you that now. So it's kind of thinking about, yes, we have different ways of putting them together to maybe improve the predictive. efficacy, the accuracy of how much they predict prognosis in certain situations, and that is important work, but the base on biochemistry kind of stays the same from that perspective. So there's nothing that I'm just trying to think about anything else that we could think about. I mean there's the new research is less about inflammation but more about things like using mitokines maybe to look at kind of mitochondrial stresses and maybe how that relates to the risk of cancer misprogression. And these are things like the UGDF15, so you might have heard about it if you went to the NMI talk last year. So there's some really interesting other avenues outside of inflammation that are important and they're emerging markers I would say. So yeah, but I would say for inflammation usually is found or obvious from the normal markers what the situation is here. But have a look, have a look at Siri and SAI, they're probably the most common ones. A lippy for lung cancer is another one that's been well researched. Yes. Oh, this is a big question. You know what I'm going to say? What am I going to say after this question? Come on, you should know what the short phrase is by now. Who first? It depends. Sorry? The answer is it depends. Yes. And I... I think somehow I managed to watch the lectures in the wrong order. I don't know how I managed that. So then I sort of, I'd done the information one before I did the gut one, which the microbiome one. So, sorry, that question was a bit probably answered. But I mean, I was, I guess I was thinking along the lines of, I mean, we are always food first, aren't we? So we're always going to work on the gut with the probiotics, prebiotic foods. But do you ever look at specific strains in terms of probiotics? for specific outcomes or not? I do very much so. So it's very much based on rational data rather than talking about just the cancer type. You know, it's about saying like Becky's case, like do you have Fusobacterium mucreatum that I need to actually sort out? Do you have a boatload of other problems? Are you heading into immunotherapy and you have crappy acromancy and other things that might influence your response? You know, the It's such a broad question that makes sense. The answer is it depends because it will depend on the type of cancer, the type of treatment that you're trying to influence, the current gut microbiome as a status. And then you then you design a plan based on that. So, for example, if I have somebody who's maybe got depleted acumansia, elevated calprotectin, elevated zonulin, high branched amino acid producing microbes and low propionate and butyrate, you know. There are some specific interventions for each of those things that I would be putting in to try and rebalance that seesaw, rather than kind of going, oh, you know what, this person's got colorectal cancer, I know exactly what I'm giving them. It's that level of ultra-personalization based, and dynamically, so that you're monitoring how much you're improving the microbiome, and then saying, okay, well, now I change to switch tack a little bit. The idea is to never throw anything generic. And probiotic foods are not really a thing unless you have a probiotic strain in them, which is a research strain with a number that's been shown to have health benefits. So kimchi is not a probiotic food. It's a fermented food. But yeah, it's important, though, because I think people will throw these things around. I think it's really important that when we say something, we mean what we say. A probiotic is a defined bacterial strain that has been shown to deliver health benefits. When administered live, otherwise it's postbiotic, in a human host. So kimchi, if you have got 20 different various things kicking around there, you don't know the strain numbers of any of them, it's officially not probiotic food because it doesn't fit those criteria. So we'll have to separate some of the times. And again, prebiotic foods. Well, prebiotic is actually a substance that specifically and selectively, not specifically, selectively promotes the growth of specific bacterial species, right? So inulin is a prebiotic, right? We can have foods containing prebiotics, but you see what I mean? There's a terminology here. This thing is really important in this gut microbiome era that we really, really get right. There are foods that contain high levels of prebiotics, but prebiotics are quite specific. And GOS versus PEGG versus inulin versus resistant starch will all have different effects and we kind of need to understand that to be able to derive the gut microbiome recommendations for people. But yes, big question and very interesting one too. And so good, and let's have a look at that. And this and I think I said to you before, I reserve to change my mind around the gut microbiome every three months because that's how fast. research is coming out and it may be that you know in another few years we might be saying something completely different for immunotherapy in the gut but that's why we need to keep up with the research it's so so important because you might find that there's a new probiotic like we used to say a few years ago don't give any probiotics with immunotherapy because the only study we had showed worse response. Now we go, well, actually, if you give CBM 588, potentially we get better response, particularly in people maybe on PPIs because we are countering some of the horrible things they do to our gut microbiome. So that advice will constantly change, which is why your best friend will always be PubMed and Research Alerts and go into conferences to update yourself because cancer is just such a fast-moving field. Thank you. a lot of research going on. Mushrooms! Oh yes, mushrooms and mushroom standardization is an interesting thing to do. I have to say I never use tropical mushrooms, that's definitely one of the things I do not use. I do always use oral from that perspective, but let's have a little bit of a look at the mushroom side of things. So in terms of mushroom species, shall we say, shall we shout out a couple and see how often we... use them let's just do a little bit of a community sourcing of information go on micronutrient hephastatera so yeah so these are brands i'm thinking species of mushrooms so think about like what what mushroom would you use in clinical practice now because then we can discuss it a little bit loads of them turkey tail okay yeah good so let's start with that one so turkey tail is one example right so turkey tails is tremendous basic law right So that's the Latin name for it effectively. So Turkey tail's got quite a good evidence base for a number of different things within the cancer support setting. So that's quite a common mushroom, certainly one of Donald Abrams' favorites. Reishi, Ganoderma lycidum. For real. When you search for data, please put in the Latin name as well as the common name, because you will find there are some researchers who will only use Latin names in publications of their mushroom data. So if you put in Reishi, then you don't put Ganoderma. gonaderma in, you're going to miss papers effectively. So do make sure that you know the Latin names of the mushrooms. You know, the most common ones that I would use are turkey tail, cordyceps, sinensis, and racies, so gonaderma lucidum. Yes, I do use the Hifis de Terra and the Micrometeor brands. I will use the individual mushrooms. I don't use the crazy Micromama type of products, and they're really expensive, but also some of the additives I'm not particularly thrilled about, although they are affordable. formulating those. And the indications for them will depend on what the overall picture is. The other thing that we use is I do use lion's mane occasionally. I will also quite often use some of the other kind of less common mushrooms. So there is a couple that are float fluid, which are really quite useful. So polyperus does, for example, or juling is another name. And so will fooling, so that's aurea cocos. So they're quite useful. for people who will retain fluid or actually need to be able to float that fluid so in my patients who are bit of dematase for example there can be quite useful mushrooms from the lymphatics perspective and obviously food wise there's a big load of mushrooms that we should all be eating as food in general from that perspective i use others a lot less frequently mainly because i would normally encourage dietary mushroom intake anyway and so some of the others like myitake I would tend to just try and get them to eat a wide variety of kind of Asian mushrooms and food from that perspective. So I don't often use that one. Again, shiitake is usually a dietary mushroom for me. So I try and use that from that side. And then shiitake I don't use as much because it has been linked to some complications for patients. And I'm not sure whether it's the mushroom itself or the contaminants within it, because like Daisy said, sometimes herbs and mushrooms will pick up stuff from the environment and will concentrate it. So where the mushroom is derived from is really important because they're great bio... accumulators of things um but shaga has been known to have some interesting effects and some complications from the renal perspective so i don't use shaga very often so um i tried shaga later on after i'd finished all of my um treatments i found it so powerful so i i powder yeah throw it in the bin it was i can't it was unholy how it tasted uh even if you put it in coffee and i just i don't know my body had said like this isn't something's not right so it's too strong for the vast majority of my cancer patients i don't that's why i don't use it so i don't i don't use it because it actually has been shown to have some gi issues there was a paper and it causing renal issues again i don't know which bit of it was the problem but anything that causes a safety flag for me is going to be a problem with my cancer patient so you're right i think i just don't tend to use it it's um it may be tolerated by some people may be brilliant for others but certainly so yeah they use um there you go that's what i show you i want to show you so this was a i mean it was a reasonably high dose but you can say so this was an oxalate nephropathy actually from the shaga mushroom and actually resulting in the poponyphotic syndrome Again, you don't know which part of the shag I've caused it, but just anything that has any complications, I do not want an oncologist calling me about. I'm not going to have. Reishi is really useful in your atopic patients. I would also use, if you want more of the reishi calming effect, I would use the spore oil. It's quite useful because of the triterpenoid content. So that's really quite useful from that perspective because you do have that more of the calming effect. Cordyceps is really great in combination with astragalus for any dips in the kidney function that are on things like platinum chemotherapy for example you will start getting kidney function declining. I know you don't work with CKD but you will sometimes see this EGFR trickle down. So in this case astragalus and cordyceps are a really good combination to have. Plus minus nettle seed. Now nettle seed is astragalus and cordyceps are well backed up by evidence. They've been used in CKD to improve markers. across the board really. Nettle seed is a traditional use, so it's not based on any randomized control trials or meta-analyses, but it's really, really useful as we call it a kidney trophorestorative. So it actually helps support normal tissue function of the kidney in the traditional sense. It's also an adrenal tonic as well from that perspective, which is why you want to have it early in the day. So if you do use nettle seed, either as nettle seed to put in your tea. You have to be careful with the dose and you have to use it early in the day because it is a stimulant. Not a kind of panage ginseng type of stimulant, but it is a stimulant. So you have to be a bit careful. But usually with a form of combination of these medications, I can sometimes approve people's EGFRs for up to 10 with good hydration and good overall management. So, you know, that's technically speaking should not be possible unless somebody has just got an acute kidney perspective. But a lot of my chronic kidney patients I will reclassify. their CKD because we're able to raise the AEGFI into the previous class for example. So yeah there's definitely so if you see a patient platinum and you see the AEGFI go from over 90, 75 to 70 to 65 you need to be acting because even though they're within the normal range from the point of view of 60 to 90 is considered to be the normal range. we need to be acting early before they become actually properly get kidney disease from the platinum and there are some really good reviews on both cord chips and astragalus from the chronic kidney perspective and kidney implications so definitely one to use for that it's also really good from point of view of um i think if you have somebody who's quite depleted and giving them a good gentle dose of cord chips is quite nice from the support perspective um what else do you want to say any other questions on the mushroom side of things. I just checked there was um there was a pdf document for the mushroom lecture but there wasn't an actual lecture is that right or have I missed something? No because the thing is they're so no we didn't do a mushroom lecture mainly because from my perspective I was like you know what you guys have had so many lectures on mushrooms I bet you just kind of need to know how to use them within the cancer setting safely and what to pick so yeah yeah yeah that's fine I just wanted to double check I haven't missed it. you haven't missed anything. Do you find also that clients that have Candida or maybe mycotoxin illness underlying they don't tolerate any mushrooms? That's what I find. I don't give them specifically for cancer because I don't work with cancer patients yet but I find that and on that note instead of turkey tail do you find things like to stimulate natural killer cells and things like that would you suggest things like biobran and colostrum zinc to kind of support? Do you rate biobran? No, too expensive, not enough benefits. For the amount of expense, I would give them mistletoe guys. Frankly, it's really ridiculously expensive. I would give them a product that I know is going to work really well. Yes, of course, it's an injectable product and it's a prescription-only medicine. So therefore, it's in my wheelhouse and not in yours. But I just think it's incredibly expensive for what it is. And the amount of data on it is really nowhere near what we want it to be. So you talk about some studies and stuff, not enough to solve them. But from my perspective, I guess, yeah, I think that if you haven't got other options, fine. I just would really worry about the financial toxicity of something like this on an ongoing basis. It is, as I said, cost-wise equivalent for me to mistletoe as an injectable product. And I can guarantee you I can get better results with mistletoe every single time versus Viobrand. How often do you inject it? Three times a week. Oh, that's good. And there are clinics in the UK. We can refer clients to your clinic and other clinics. Yeah, there are plenty of clinics around. If you go onto, I think there's a mistletoetherapy.org.uk, there's a couple of clinics there. We cover patients, so we're just about to have one of our nurses who does a lot of our IV and injectable work. He's about to become a nurse prescriber. He's going to have a supervised mistletoe clinic. All of our doctors prescribe mistletoe. That's including our consultant oncologist who loves mistletoe. I've got a book on my reading list at my desk to read up on it. But yeah, OK, so that's and then as an alternative, people that can't tolerate mushrooms, colostrum, zinc. Yeah, so I don't tend to use cholesterol very much. I mean, zinc is, to be honest, I give zinc carnosine for the vast majority of my patients on chemotherapy or some form of zinc. If you can't use zinc carnosine, you can use anything else. But what I'm trying to say is, unsurprisingly, they're going to have a compromised intestinal barrier and therefore they will be on zinc. And a lot of the time they don't consume enough from a dietary perspective because their oral intake isn't fantastic. And with the mucositis, you want to have that on board. So I already do that anyway. From my perspective, if you were doing anything else and you had other options, I mean, you can tricolostrum i would go to herbs really and that's just probably because of my practice because i have it in my wheelhouse you know herbal medicine so powerful i mean let me give you one example it's not actually an immune example just because it's a laugh really one of my cancer patients today a bit of an emotional breakdown really this week so she's um she had uh this week it was the last week um she's had a lot of trauma in her background anyway and and just coping with A recurrent tricky cancer diagnosis was really difficult. And so she's got therapy support, so she's ongoing with that. So I was like, okay, go talk to your therapist. But she was actually acutely, visibly anxious and distressed. So I was like, okay, we'll just give you some herbal medicine. She was like, oh, yeah, fine. And then she calls me about three days later, and she goes, so Dr. Nhi, I was so relaxed. If I was sleeping on my echocardiogram, I'm pretty sure you've slightly upped the dose. But very seriously, and I saw her, you know, probably a week to 10 days afterwards, and it was that immediate in effect. And don't get me wrong, she's doing other things, but she was doing those other things on top of it. That herb gave her, or herbal meds, gave her nervous system enough room to breathe, to be able to do the other interventions to self-regulate herself out of a really, really deep problem. So I think, to me, herbal medicine is an immune side of things. I've treated pneumonia with andrographis and other herbs and I've gotten the CRP of 43 down to normal within three weeks on just herbs without having to use a single antibiotic. So really powerful stuff. So you don't have to go to mushrooms necessarily. If people don't tolerate them, you're right. There will be people with chronic candida who will develop anti-candida antibodies that cross-react with the mushroom cell wall and therefore will not be helpful. So there's definitely a phenomenon for that. And mycotoxins as well, people ask. Mycotoxins again, it's the same mechanism because they've developed some antibodies from the point of view of fungal cell, antifungal cell antibodies will cross-react, so it will be a problem from that perspective. But a lot of our patients, probably less so Daisy where you're working right now, will tolerate mushrooms reasonably well, particularly if they're worked up carefully, if they're good quality, and if they don't try random things like high-dose chaga powders. see people trying all sorts of interesting things and possibly to their detriment. The other thing I would say from a mushroom perspective, just be, I would be quite reishi forward if you had somebody with a big history of autoimmune disease and cancer, rather than trying other mushrooms, because reishi is really good at immune regulation, rather than, so I would probably be a bit cautious with overcooking it with people who have an autoimmune disease and cancer at the same time. particularly if they're on other interesting medications. So that's where Reishi does have its really good place because I've never ever seen it worse than an autoimmune reaction. It's actually really good from that perspective. and traditionally used as well in TCM in China for that. We talked a little bit about other bits and bobs, so Daisy's asked a few other bits and so yeah I mean CRP, yeah we talked about the panels that I mean NLI and PLI is just full blood count so you don't need any more than that to calculate them and CRP, ESI and LDH you should be able to get from things like Randox for example Yeah. You know I know MediChex does some of these things. I can't remember if they do total LDH. We don't use them very much. Sebo testing-wise, it certainly depends on what device you have available. The key thing for you guys to know is that if you're using something that's not a medically registered device and you're expecting gastro to treat, you'd better be using a proper breath test, as in a proper three-hour curves, because not a single gastro will treat on the basis of a pebble. or marble or whatever we've got yeah but it's tricky with hydrogen sulfide and yeah i know but but with hydrogen sulfide you might not be referring for that necessarily you know so what i'm trying to say is that um if you're going to refer to medics for treatment use a medical test yeah don't bother using any of the stuff that's not licensed as a medical device because you're just going to get laughed out of the house and it's just it's just not good practice really for you as clinical practice you can use whatever you want to do i've never done a life code gx nutrition nutrition and expertise practitioner program so i don't know other people have done it and think it's wonderful so it's very expensive though yeah i haven't looked at it properly yeah they're tests i mean i'm not saying they're not useful daily but when you do them obviously even if you've got a snip and it says you might need more of this or less of this and you need to look at their diet and what they've got anyway because it doesn't obviously mean that they're not getting it's real time and i think i will always always please come here with a blood test and symptoms and other things because i used to do them quite a bit more when i was at alcon but then i stopped doing them really afterwards because they're some of them are almost as expensive as a microbiome test and i'd rather spend the money on that yeah yeah yeah 100 and i think that's it's because the thing is nutrigenomics is useful and people have budget great however it's always a risk don't forget it's not real-time expression it's not what you've got as a real-time biochemistry so i've had patients who come to me and they've got like two dutch tests in their menopausal on aromatase inhibitors and what's the point of doing that zero and a nutrigenomics test but nobody knows their crp vitamin d and some of the basic biochemistry and i was like what the heck is this and that's a bet worst example of how not to use functional medicine in cancer i think that was partly inspired by my own uh i think you see it in the next question because i've got some delicious deletions on the actual genes you mentioned on one of the lectures so that was an interesting five minutes so you don't have to guess with deletions right you just don't have it just completely outright you don't produce blue cyan or something like that so no you you do so i think if you've got so if you've got a gstm1 and gstt1 deletion those are the two yeah so it's glutathione S-transferase. So S-transferases have no role in creating glutathione. They transfer glutathione. So they do the glutathione conjugation bed. Okay. This means that all of your metabolites rest on GSTP1. Okay. That means that sulforaphane is basically something that we should be taking daily from that perspective. So I've got a GSTM1 division and I've got a GSTP1. So I've got one and a half genes. You've got one gene. functional. In fact, if you've got all three knocked out, the fetus would not survive. Like, GSTs are so, so important. But you activating that remaining GSTP1 and not putting too much load through that pathway is therefore that important. But of course, the lesion is the GSTP1. I know, but you've got three genes, okay? PM1, M1, T1, P1. Yeah, okay. If you had all three, you would not be here. Yeah. got a TNM deletion, fine. The P, therefore, is doing all of the gliathione transferase work for you. That's why things that activate GSTP1 expression and help maintain optimal levels are important, so sulforaphane being one of them, because it will have a multiple effect. It will also activate NQO1 and a few other things down the line. Obviously, reducing toxic load is also important, so we're not trying to rely on gliathione conjugation from that perspective. But it doesn't mean that you don't make gliathione. It just means that you are you're finding it trickier to do the same conjugation basically because you're aligned with a single enzyme variant rather than three enzyme variants from that perspective. But, you know, that's that's the important bit. The other one, the final question is about referring people with symptoms and risk factors. Yes, I've had a few of those since starting this course, maybe three or four clients. because I'm not quite there, I'm not quite, I don't feel that I'm ready to practice any of this and safely I shouldn't be. Have you, do you think what's the safest form of words that we can use to strongly encourage them? I think it depends on the client, right? Some people freak out, some people prefer to know. But also you're not diagnosing, so that's important. So that's like you can't give them diagnosis, nobody's given them a diagnosis, you just thread flags. So I I would say using neutral language such as there are a couple of things that are a bit concerning for me, and I'd want to make sure your doctors looked at them properly to rule out any causes for whatever's going on right now, or to look at it more deeply to find out what is going on for you right now. You don't need to mention anything more than that. We can say, I am concerned I'm referring for that particular reason. And then if you say, they'll say, oh, what do you suspect? I can't give you a diagnosis. We don't know what's going on. You need to require further investigation. You need a proper medical review. but you can say it's just something that I know is not within normal range and therefore I'd like you to get it checked out so keep it as neutral as possible because the the nobody can come back and tell you oh you told me I have cancer and my doctor says it's a load of rubbish so I would just say use the word that I'm you know I'm I'm I would like to get a medical review of these symptoms or these biomarkers to make sure that we know what's going on with you you know they're just really really neutral very vanilla because it's a bit different if you see really high out protecting or blood in the stool in on a stool test so that's you know based on these you know yeah it checks out but i think kind of putting two and two together on other things and you want to refer them i'm finding it a bit tricky at the moment but i think i just think use neutral words but just express your concern because the thing is if they trust you as a practitioner and you're concerned they will go and get it checked out however there are patients who are just you know i mean we had one patient who's just so disengage with his well there's two components to it one is that he's actually unwell so he's just he's had a um he's all my patients one of our mt patients but um he has a history of prostate cancer and his psa has been slowly creeping for the last few months then latest tests that our mt has done shows hypercalcemia right so not a happy place to be if you have a history of prostate cancer so i can't tell him that his prostate cancer progression nor can and his NT at the moment, but what I've done is I've sent him for some extra bloods, and once I've got those bloods, there will be an urgent medical referral that's going through, which we've already asked him to go and talk to his GP and oncologist, but whether he is or he isn't going to do that is a really tricky thing. But I know that I will need to discharge my responsibility, so I will be contacting his medical care directly because it is actually, if the calcium is high enough, it's actually a medical emergency. So you do need to know your cut-offs really well. And electrolyte abnormality... in anybody with cancer. I mean, anybody anyway, frankly, but particularly anybody with cancer requires an urgent medical review. So if you see a hypercalcemic patient, you'd better have contacted somebody on the medical side. For all of you, people with cancer always have an extra kin on file, always have the details of their treating medical team. Because sometimes you will not be able to get hold of the person. Your client might be AWOL for whatever reason. They might be really sick. Something else might... have happened you will need permission written consent ideally a document on your system to contact somebody in an emergency and ideally you'd contact both the next of kin and the medical team so you you work if you do this work you will be working with profoundly sick people going through the toughest times in their lives and you need to know when to escalate that red flag really quickly um because it's it's i sometimes it shocks some of the nts to start doing this work when they've been used to kind of mildly abnormal blood tests and suddenly ALT comes back at like three oh no somebody said to me my goodness the ferritin is 500 I'm like yeah I've seen 1200 before but it just you will get these very abnormal results if you work in this particularly with patients with advanced cancer so you need to know how to action them safely and how to escalate them and you need to have procedures in your paperwork in clinic so that you're able to say you've you've got the consent to quantum you know exactly who you're talking to and you can give all the relevant information to make sure the client is protected and safe. But yeah, not an easy one. I think I would say just keep it as vanilla as possible and talk about concern and getting checked out and medical reviews and that sort of thing. And you will find a comfortable wording that works for you because everybody, all of us speaks. and what works for me is a phrase might not work for you. Good. Thank you. Any more before we close? There was one thing, nothing to do with this course, but you've mentioned some advanced modules. And you do one on breast cancer and you do one on bowel cancer as well. Well, that's in planning at the moment. So I'm hoping that's going to be out next year. So that's currently in progress is how I would describe that bit. And so hopefully there will be one on bowel cancer because we also need one on gynae cancers, for example. There's a few others that we definitely want on prostate cancer, given how very, very, very common it is. but what I'm trying to do is I'm trying to do APMs where you can get access to also to information from people who work in conventional oncology so in the breast cancer course for example Dr. Penike Hayumi who's a consultant clinical oncologist is on that course providing information for you from that perspective so that you actually get to hear from people who are working within that setting you get more of that access because I think it's really really important when you're looking at the depths of cancer in particular so for colorectal cancer I've got some connections so I can put pull in for example tiny cancers i've got somebody i'm still you know obviously robert thomas will be good on prostate how much he's going to agree to do of course i'm not entirely sure but um but you can you can kind of see what i want to try and create to make sure that you've got um access to several people within the conventional mdt and their perspectives because you need to understand the conventional mbt perspective do your job properly in the advanced practice module really yeah goody okey dokey in which case i'll let you go off and have a wonderful friday afternoon thank you so much everybody which is what angiogenesis is. ________________ 4.1 Circulation and tissue architecture (invasion, angiogenesis and metastasis) Hi everyone and welcome back to Systems Approach to Cancer. Today we're going to be talking about circulation and tissue architecture and for us it will really cover angiogenesis, which is the formation of new blood vessels, invasion, metastasis and cancer stem cells or CSCs for short. So when we're looking at healthy circulation tissue architecture the aim for us is to promote normal blood flow tissue perfusion healthy coagulation and also support the inhibition of angiogenesis and metastases which also involves the work with cancer stem cells as they're the part of the tissue architecture of the tumour and also of course are involved in establishment of tumours and distant sites as well. So I think it's important for us to remember that normal circulation coagulation is essential in cancer. Cancer is a hypercoagulable state, so there's a high risk of clots such as DVT, deep vein thrombosis, or PE, pulmonary embolisms. So it's really important for you to be on alert for signs and symptoms and advise clients to seek immediate medical input. And for DVT, the key signs and symptoms are the swelling of the leg and calf on one side, pain that might worsen when sitting and standing within that particular calf, and warmth and redness of the leg. a leg usually unilateral. The PE can present a sudden onset of breathlessness that can't be explained and sudden sharp chest pain particularly on breathing in and coughing up blood. So if any of your clients experience these symptoms they really need to seek medical attention urgently because particularly PE or pulmonary embolism can be fatal if they're big enough. It's important to test and target fibrinogen where possible because having elevated fibrinogen levels can be tricky because it can promote, again, a hypercoagulable state and systemic proteolytic enzymes like natakinase can be useful in lowering fibrinogen when it's elevated. Some of our clients might be on prophylaxis or treatment with anticoagulants such as warfarin, oral anticoagulants such as rivaroxaban, etc., or injectable low molecular weight heparin. So if someone's telling you they're injecting themselves daily in the tummy, then quite often it would be a low molecular weight heparin to prevent them from clotting. And usually these clients might have already suffered an event, like had a previous clot in the lungs or clot in the calves. The impact of treatment should also be considered in terms of circulation. So we know about lymphedema and that doesn't just apply to breast cancer and removal of the axillary lymph nodes. It also applies to some of our pelvic cancer patients where actually their lymphedema is much more the lower limb lymphedema. And also we need to consider that there would be poor healing post-surgery if circulation is impaired. And of course, that's one of the reasons why diabetics commonly have quite a bit. of an elevation in issues post-operatively, including poor tissue healing. And you need to consider appropriate interventions. Again, regular movement is important because it's supportive of normal circulation and manual lymphatic drainage under lymphedema nurse guidance or input from the team. So this is just to remind us to go back to our original six hallmarks of cancer that here we're going to be talking about angiogenesis and invasion metastasis, so two very very important original hallmarks. So just reminding you that angiogenesis is a growth of new blood vessels to supply the tumour with oxygen and nutrients that are needed for survival and the control of this process is really through the balance between angiogenesis promoters such as VEGF or BFGF, and inhibitors. And the molecular base of angiogenic switch includes increased production of things that say yes to angiogenesis and or loss of inhibition. And these factors might be produced directly by tumor cells or the inflammatory cells within the environment or other stromal cells within the tumor architecture. Again, you don't need to know any of this stuff in detail, but I think it's really important for us to remember that this is how the signaling occurs. So FGF or VEGF or PDGF sometimes, angiopoietin 1, combined to the receptors, it then activates intracellular, the signaling pathways within the cell, quite often transduced by very similar molecules like PI3K-ACT or through NF-kappa B, for example. And then that leads to angiogenesis. And so it's important for us to also consider the fact that you will see a number of molecules involved in inflammation here, such as you can see IL-1 and IL-6 and F-kappa B and COX and LOX. So important for us to consider that inflammation plays an essential role in angiogenesis, which I'll cover in a minute as well. So the key activators of angiogenesis is hypoxia. Once a tumor grows beyond a certain size, it really cannot grow without sprouting new blood vessels, which is what angiogenesis is. And so hypoxia, or the tumours being starved of oxygen, increases VEGF, which is vascular endothelial growth factor, via HIF1-alpha. And so what happens is the hypoxia, or low pH within the tumour microenvironment, activates production of HIF1-alpha, that will then activate VEGF and lead to angiogenesis. The important thing to say is that those new blood vessels that are formed are not normal blood vessels. They're quite leaky. So tumours are quite often quite edematous, really, because there's quite a lot of leakiness. They're not normal, well-formed blood vessels. And so, of course, we know that from the medical perspective, there have been attempts to target that with things like bevacizumab, which is an anti-VEGF monoclonal antibody. and to see if we can get a normalisation of this. So it's important to understand that local hypoxia within central areas of solid tumours promotes angiogenesis for their own survival and is one of the major issues contributing to treatment resistance because if we don't have good circulation, we have hypoxia, it fosters us not being able to access the correct treatment effect and treatment resistance. So, the other thing that we have already mentioned to you is that inflammation in the tumour microenvironment is also essential for activating angiogenesis and meta-inflammation or metabolically driven inflammation also plays a role. This is just kind of an overview diagram of every different thing you could possibly see in a tumour. There probably will be others, but it's important for us to realise that tumours aren't just single lumps of cancer cells, they have all sorts of cells associated with them. whether it's the cells of the immune system, such as macrophages, M1 and M2, as we discussed, the M2 ones have particularly the pro-tumor effect. The T cells, so either Treg cells that immunosuppress and Th2 cells immunosuppress, or CD81 killer cells and Th1 cells. NK cells are actually not on here as well, but that would be part of it. As well as things like cancer-associated fibroblasts, the stromal cells. that will play a role in secreting some of those really important factors that can affect invasion and angiogenesis. And myeloid-derived stem cells, and that's MDSCs, and they're the ones, again, you can see. secretes VEGF and FGF2 to promote angiogenesis within this area. So don't think of tumors as just bags of cancer cells. They're actually very complex, almost mini organs in and of themselves that have multiple cell types. And obesity and cancer, again, we'll look at it in a little bit more detail in the metabolic talk, but actually we've got to remember that this inflamed central adipose tissue has... has a significant effect on inflammation, on generating things like adipose-derived tumour-supporting cells and systemic metabolic dysregulation that leads to increased angiogenesis, metastasis and chemo-resistance and growth promotion. So it really, really is important that we try and keep our patients within a healthy BMI range, but also the healthy... adipose central fat levels. That's really, really important. So here's a list of some of the important natural compounds that may play a role as angiogenesis inhibitors. Again, this is not an exhaustive list. It's some of the most common things that come up. So curcumin, artemisinin, EGCG, resveratrol, ginseng, thymoquinone. from Nigella sativa or black cumin seed and tocotrienols, which is part of the group of vitamin E compounds. And again, as I said, there will be others who will have this sort of effect, but they're the most common ones. And as I said, here is a list of various different flavonoids that might also play an effect in phenolic acids. So things like rosmarinic acid, ellagic acid, epigenin. But we've got to remember that, again, when we're thinking about it, you've got to remember that if it's an in vitro study, That's nice, but it actually might not have sufficient clinical effect because it might not have used the right concentration, the right cell type. And we don't really know whether it actually has the same clinical effect in vivo. So I would caution you in kind of over interpreting the data. And here is a lovely diagram that talks about several different points in which we can look at targeting angiogenesis and invasion pathways with natural compounds. But again, remember that a lot of this is based on in vitro data. So it's really important that we keep ourselves up to date with any animal and human studies to see whether we're actually having a proper clinical effect rather than just showing cell inhibition. So we can see that again. And same things come up time and time again. You will hear it. You will see resveratrol, quercetin, curcumin come up a lot. Carnotic acid comes up as well. Ginseng, green tea, so that's your EGCG and other components of green tea. And hyperforin is something that comes from St. John's Wort. So you will see there's the same players. And those same players have this multi-pathway effect and multi-hallmark. So it's important for us to actually know that sometimes with just a few, both food interventions and supplemental interventions, we might be impacting on a number of different pathways. But it's important not to over claim clinical effect. So this is just a quick reminder of what happens in vasometastasis. You have effectively a subclone that forms out of the tumour that has acquired the ability to migrate through the basal membrane. and part of this is what's called epithelial mesenchymal transition, EMT. Then it moves through the basement membrane, really squeezes into the blood vessels in the gaps between the different endothelial cell lining. And then we can have something called introvasation, which is where the tumour cells are then in the circulation. They're often covered in platelets and have other associated cells with them so they don't travel alone. and then when they reach target tissue, they will extravasate, which means exit the circulation and then form a metastatic deposit elsewhere. So, as I said, EMT in solid tumours plays a significant role, and invasion of the extracellular cell matrix initiates this cascade. You first started to, you know, when tumour cells haven't undergone full EMT yet, they're quite stuck to other tumour cells, they're not going to be invading. the ECM. But actually, at first, they kind of shake off their neighbours. They loosen up the tumour cell-cell interactions. So that involves something called the adhering proteins. Then there might be secretions of MMPs, and that's matrix metalloproteinases that degrade the matrix and basically makes a little bit more room for the tumour cell to move. And then you've got the tumour cell attaching to these novel components of the extracellular matrix that have been exposed. and migraines drags itself along to the blood vessel where it can then enter the circulation. So key pathways in EMT, I always think that it's quite handy that they've named some of these because when we think about EMT, it's a cell that goes from stationary to crawling. So think of it as creepy crawlies. And this is the reason why we've got snail and slug as transcription factors within these pathways. So I find it quite useful they've named them like that because it really... reminds me that these are the transcription factors involved in this EMT transition from being a cell that's connected to its neighbours and stationary to a cell that's dissociated from its neighbours can break off and crawl away into the circulation. So snail, slug and twist are the key transcription factors. There are others as well. And they're affected by, look at this, TNF alpha and R6, so inflammation. They're also affected by hypoxia, and that's HIF-1-alpha. And TGF-beta is part of the tumor microenvironment. So it's really important for us to remember that these are similar pathways than what we talked about, and they all play a role in Bayesian metastasis as well. So it's all linked together. That's the reason why I like the systems approaches, because it's not about targeting one thing or even separate blocks of things. It's about understanding the interrelationships. And MMPs play a significant role. There are lots of different kinds of them and they will play a role on tissue invasion and introvasation, so it escapes into circulation. They can play a role in angiogenesis because they release. that might be stored around the tumour in the matrix, and they can also regulate inflammation in the metastatic niche. So they are very, very important. And just to remind ourselves that it isn't kind of by magic that tumour cells will then just go off and attach somewhere. The original tumour site actually grooms tissues for metastasis, almost prepares a landing pad for that metastatic clone to land. And it's important for us to consider that all of this actually harkens back to other... the things we've discussed, such as immunosuppression and inflammation, angiogenesis and vascular permeability, so that's those leaky vessels, lymphangiogenesis, and that's actually looking at recruiting lymph vessels rather than blood vessels. and then organotropism that's affinity for particular organs so as we know liver, lung, bone are particularly favoured organs but then different tumours have different affinities actually and reprogramming because actually when the metastatic clone lands somewhere different it then has to reprogram its environment to be conducive to growth and some key pathways in cancer stem cells are listed here. So cancer stems, as we know, we think that they are important in solid tumours because they self-renew as well as generate other cancer cells that can then go off and grow and proliferate. So it's important because cancer stem cells can be a major pathway for post-treatment recurrence. and also treatment resistance because they're not proliferating so quickly as other cells. So they can actually go dormant and then be reactivated. And it's important for us to think about some of those pathways. And the pathways involved here are Wnt, Notch, P10, and Hedgehog, or Sonic Hedgehog. So when you see SH as in S-H-H, that's Sonic Hedgehog pathway. And it bites this receptor called Patch. and activates a number of things downstream that can help the maintenance of cancer stem cells. So I quite like it because it's one pathway you might remember because it's funny. So when we're thinking about natural compounds that might have potential for targeting pathways in cancer stem cells, again, this is just a list that I've gotten from the literature by reading various papers. It's not an exhaustive list. There are others. But the key thing, again, to... to caution you on is some of these have in vivo studies but lots of them don't so we can say that they have potential but we we can't at the moment say okay yeah this has been used in a randomized control trial and we could actually see measurable clinical effects on outcomes because that's what we're interested in I'm not particularly interested in inhibited the particular pathway I'm interested whether that inhibition has resulted in our client having better outcomes, really. Is it better progression-free survival or better time to, in metastatic cancer, better time to the next therapy being needed? You know, that's what we're really interested in, supporting our clients as much as possible to have a good clinical outcome. But the top of the pops you've heard from me before, you know, curcumin, quercetin, resveratrol, terastilbene, which is a methylated derivative of resveratrol. resveratrol has slightly different actions. EGCG, sulforaphane, I3C, and DIM, which are basically glucosinolates and glucosinate metabolites. Genistein, lycopene, a solid acid that comes from Tulsi or holy basil, parthenolide, which comes from few of you, 6-sugol, which is a ginger derivative, isoliquarytigenin, even though I can't pronounce that, comes from licorice, and of course, tocotrienols, which we talked about before as well, but there are many others. those. And I just want to remind you of the multi-targeting effect of most of these natural compounds. Unlike medications, which have relatively specific target with minor off-target effects, really natural compounds affect and wash over a number of different pathways. They're not a single pathway targeting thing. So actually curcumin covers all the hallmarks, new and old, for us. So we actually know that it has an effect on a number of those things. And we've seen that in clinical trials, it synergizes with therapy and can have a clinical outcome effect. So this is where we can stand on more solid ground. But you can just see the curcumin affects a number of things from cancer stem cell associated pathways like B. ticatinny and sonic hedgehog, to cell cycle, apoptosis, metastasis, angiogenesis, tumor-promoting inflammation, cell cycle effects. And I'll also show you when we come to talk about genomic stability and sort of methylation, it even affects that as well. So resveratrol and cancer stem cells, again, you can see a number of different effects on things like not-significant PI3K-ACT pathways. And VEGF in terms of... and FGF2 in terms of angiogenesis. So it has a number of different effects. EGCG again covers a huge amount, so this is just something for us to remember. I'm not going to go through a slide for each of these compounds, but if you're interested in them, you can just read up on them using reviews on PubMed. A solic acid that comes up less frequently, so we just want to show you again the multitudinal pathway effect that that has. So acyclic acid comes from Tulsi or holy basil and we can affect anything from proliferation to apoptosis to epigenetics, angiogenesis and metastasis. So again, another thing to consider for us. Now, again, this list is not exhaustive. There are many, many TCM herbs that are used in cancer support but there are a few things that come up time and time again that you might hear about. Pan-X, ginseng and ginsenosides I find particularly valuable for HPA axis and fatigue support but it does have more multiple effects on cancer pathways as well and hallmarks. Astragalus membranaceus and formaldehyde, and it's one of, again, it's just a selection of the different compounds. We know these are complex herbs that have hundreds of various different compounds. So it's important for us to remember we're just isolating a few things if we just give one compound, but when we get the whole hub, we get the full effect. Pastragalus I find immensely helpful for immune function, HbAXA support as well. So it is an adaptogen with an immune supporting function. Magnolia, again, you would have heard about Honokyo, but there's also Magnolol. And this is very valuable to sleep and anxiety support. And again, it will target a number of cancer stem cell pathways as well. But again, we must remind ourselves, we don't know about the clinical outcome effect, but we do know it might be helpful for us biochemically. So just make sure we don't over claim. Salvia, multiorizodone, shen and tanshinones, again, huge amounts of pathways being targeted through those. And I do use it as a part of my herbal mixes quite a bit. And then tryptorhynium, where 4DI or thunder god vine has compounds called. tryptalide and celestrol of which there's a lot of interest recently in cancer so I think it's an up and come and again we'll start hearing about it a bit more as we go along but it's not an exhaustive list I just put down a few things you might hear about in literature or when you go to lectures when you communicate with other practitioners so just something to be mindful of of all those I probably use the top three a lot and the others kind of less frequently but I do use the top three quite a bit. The great thing is that even though we, you know, TCM practitioners, you're not going to be using them in the same way as TCM practitioners would. But we do have those valuable in capsule form via companies such as Time Health and some of the usual supplement companies. Unfortunately, Econugenics has kind of cornered the market on Hanokia or from Magnolia. So and it's very expensive. So I will be looking for alternatives for cancer patients because. Okay. cancer clients because it is prohibitive in terms of the amount you need. And you really need two to four capsules a day to have an appreciable effect. So it becomes very expensive very quickly. So just as a summary, be aware of the increased clotting risk in cancer. Please just be mindful of that. I know most clients who would see you would have been told about the increased risks, but it's always important because sometimes clients tell us things they might not tell other people. And we need to... to remember that there are a number of natural compounds that cover angiogenesis, invasion, metastasis, and cancer stem cell targeting, but we're not yet sure about the clinical implications for these. And I haven't specifically highlighted some of the other things that we know about in terms of metabolic pathways because it's the next section. So just pick a few from the list that we've got that you can get really familiar with and properly read up. So my top list to start with would be curcumin, glucosinolates, and that's your sulforaphane, I3C, and DIM, gin-gin. its components quercetin tocotrienols resveratrol egcg and thymolquinone or nigella sativa of the others i said again you you might consider reading up on on some of the tcm hubs as well in terms of looking at ginseng or looking at magnolia and and getting up to date with that but this is really where we'd start with because it's going to cover you for a huge amount of knowledge and clinical applications thank you for listening Thank you. ________________ 4.2 Understanding Hormonal Influence on Cancer Hello and welcome back to Systems Approach to Cancer and today we'll be talking about the roles of hormones and hormone modulation within the cancer setting. So here as you can see we're right towards the bottom and we're going to be talking about supporting and modulating the hormonal environment and that means addressing production, transport, tissue sensitivity and detoxification or PTSD. which is an acronym created by the IFM. So looking at these processes and their relevance before, during and after conventional treatment. And in this section, we're going to be covering sex and thyroid hormones in more detail. Although, of course, we'll be covering a lot more of those within the advanced practice modules next year as well. And insulin will cover metabolic and mitochondrial health. So key cancers for the sex hormone component. are breast, ovarian and endometrial and to a certain extent prostate cancer. And the reason I say to a certain extent is because actually it's not really as clear cut as people have been led to believe and it isn't just autosostrome driven. So just a reminder about breast cancer and its key drivers and we know that obesity and alcohol are really key lifestyle drivers for us to address and there is a significant proportion caused by radiation as well. Endometrial cancer, again, the obesity being a very, very important cause for us, and it's important to remember that PCOS is a risk factor for endometrial cancer. And the reason it increases the risk is that because these women don't ovulate in a normal setting, we have unopposed oestrogen without normal peaks in progesterone that occur post-ovulation. which means the prolonged exposure to unopposed oestrogen can cause endometrial hyperplasia and may lead to endometrial cancer. So if you meet someone with endometrial cancer and have a history of PCOS, you can see how that might have developed due to these anovulatory cycles. And also another really major reason why we should be tackling PCOS as early as possible so that we're not landing in endometrial cancer territory. So ovarian cancer, again, just a quick reminder in the fact that the risk factors include some inherited risk, but again, the same thing comes up, obesity will come up, other medical conditions such as endometriosis and diabetes, and of course, HRT, smoking, asbestos and radiation. So let's start looking at the PTSD parts of the oestrogen pathway, and let's start looking at the production of oestrogen. And of course, we know about the steroid hormone pathway, which is... starts with cholesterol, that goes down to proglanolone and down to DHEA. And DHEA then goes off to make androstenedione. Now, of course, all of these pathways, you could remember, they're not as linear as that. They all interconvert between each other. And this is a much oversimplified view of it. And then this androstenedione and testosterone, which can interconvert between them, can also then be aromatized by CYP19A1. to estrone and estradiol. And of course to remember we have three types of estrogens within our body. Estrone which is E1, it's mainly adipose tissue derived. E2 and E3 and E3 is triolose, the weakest estrogen. So let's talk a little bit about the first few steps in the pathway when we get to the androgens. So when we get to DHEA and androstenedione and this pathway as you can see is much more complicated and shows the interconversions. So When we're thinking about what might be driving prognolone going down to DHEA and progesterone going down to androstenedione for example, we know the significant aspect of increased androgens as we know from PCOS is hyperglycemia and hyperinsulinemia and obesity. So we know that androgen production, so DHEA and androstenedione production can be significantly driven by those. And things that are inhibited are, you know, atagenin and polyphenols, for example, and there is some role for licorice roots as well in some cases. So, as we can see, the CYP17A1 inhibitors, there are two steps to CYP17A1, you can see here. First is the 17-hydroxylase step, and the next bit is the 17-20-lyose. So the same enzyme, CYP17A1, catalyses both steps that take you from progenolone to 17-hydroxyprogenolone. and then 2-DHEA. It's just got two different enzyme activities to it. So this is something to bear in mind. So of course when we look at CYP17A1 SNPs for example that might be potentially increasing the activity of this enzyme. Or don't forget the metabolic drivers, the hypoglycemia, hyperinsulinemia and obesity. We need to then target those. And there are also some more specific CYP17A1 inhibitors. But the research within the series is still very early. It's mainly animal cell studies. So apigenin and resveratrol have been shown to have effects on CYP17A1. And with resveratrol mainly showing effects on either the expression or... of CYP17N1 or the 1720 LIAIS activity, which is step two in this pathway. So the key point is we can use these, but we don't over rely on them because we need to address and correct the drivers. So don't forget the metabolic dysfunction within this needs to be corrected. And you've seen from the epidemiology review just now that it is obesity, obesity, diabetes. So you can see that the sex hormone. Driven cancers are deeply linked to the metabolic drivers. So let's look at the next step in CYP19A1. This is when we take the androgens and we convert them into oestrogens. So all oestrogens start out as androgens and that's male sex hormones. And so the aromatase we need to again tackle in the same way. We need to reduce influences that increase aromatase action, that's alcohol, obesity. insulin resistance and inflammation. So again you can see the same key players come up time and time again. And there are some specific foods and compounds that may inhibit aromatase, all of them to slightly different degrees at slightly different concentrations. But things we do know is lignans from flax seeds, although we know also that of course entrolactone, which is a metabolite from flax seed, also has phytoestrogenic effects as well. And the same goes for azoflavones from soy. and that's genus D and A's in particular. Mushrooms can have some aromatase inhibitor effects, resveratrol, apigenin, chrysin, grapeseed extract with its proanthocyanidins, and green tea. There are plenty more as well, and there's an additional paper I will post for you which is a beautiful overview of natural aromatase inhibitors. We've got to remember that many polyphenols have this action, so high phytonutrient, colourful, anti-inflammatory diet. that is going to have a really good low glycemic load, is going to be targeting a number of these different aspects to upregulate aromatase. So just keep that in mind. It all has to be within the context of the right nutrition lifestyle. This isn't about just giving people isolated compounds. So going back to the PTSD of oestrogen, we've talked a bit about production. And now we're going to be talking about estrogen transport. So the majority of estrogen is transported in our body, as well as testosterone, by the way, via SHBG. And SHBG is increased in pregnancy, hypothyroidism, when you get given estrogen, so HRT or contraceptive pill. And it is decreased, and therefore more free estrogen is available through obesity, androgens, insulin IGF-1, corticosteroids, progestins, and hypothyroidism. And 30% that isn't bound to SHBD is bound to albumin and 1% circulates free. And this is the active hormone. You could remember that it's only free testosterone, free estradiol, for example, that are active. Bound is not accessible. It's a bit like having something in your bag. You're not going to be able to reach it without opening the bag and getting it out. Some literature associations have been shown between specific SHBG SNPs and breast cancer, which again is interesting to us because we're not just looking at production SNPs, like aromatase SNPs and CYP17A1 SNPs, but we're also looking at the transport SNPs. So each aspect of the pathway can be affected, but both genetic predisposition, of course, and anything that washes over it in terms of nutrition and lifestyle and stress is an exposome. So how do we increase this HBG to lower free oestrogen? That's really a vegetarian plant focused lower protein diet. Weight loss, decreased visceral adipose tissue and unplugged metabolic drivers, and that includes insulin IGF-1. And time-restricted feeding can be very valuable here, for example, in the 16-8 regimes where you fast for 16 hours and eat within the eight-hour window, alongside, of course, other dietary and lifestyle changes. And if the client is hypothyroid, it's important that their thyroid function is optimized. It's really, really important. So thinking about the other part of PTSD or oestrogen, we've talked about production and transport. We're now looking at sensitivity and tissue sensitivity. The activity to estrogen is really done through two different kinds of estrogen receptors. And of course, they will also be interacting with other signaling pathways, such as progesterone and testosterone pathways. But we have two different kinds of receptors, ER-alpha, which is basically basically stimulating proliferation survival and is an absolute key target within breast cancer. And there are several SNPs within the ESR1 gene associated with breast cancer. So ER alpha, estrogen receptor alpha, is the gas. When the estrogen binds to it, the whole estrogen receptor complex translocates to the nucleus and sets off many, many pathways that affect proliferation survival of cells. ER beta has a different effect. It can interact with or inhibit ER alpha, an androgen receptor function. It can suppress cell growth and influence the responsiveness to endocrine therapy. So it's important for us to know that ER beta isn't actually a full-on, let's press gas here, actually it's more of a moderator. It's like a little mini break sometimes. It acts to modulate the effects that estrogen has on the cell. by the ER alpha receptors. And we've got to note that phytoestrogens preferentially bind to ER beta, which is the reason why we're thinking they're more protective rather than harmful. However, this is not specific. So there will be some ER alpha binding, even if they do prefer binding to ER beta, hence the whole grave controversy. Xenoestrogens, so that's foreign estrogens in terms of pollutants. and endocrine disrupting chemicals play a significant role here. Of course, if we can mimic oestrogenic effects via these compounds, that's huge. And of course, this is where we look at detoxification, Toxicload quite specifically, within any hormone-driven cancers because it does play a part. And here, it will be everything from organic pollutants to heavy metals, including things like cadmium, which is considered to be a bit of a metalloestrogen. So let's now look at detoxification or estrogen metabolism. And of course, we've got the three buckets we can go down. We've got the 2-hydroxy, 4-hydroxy, and 16-alpha-hydroxy. Sorry, I dropped out there for a minute. Okay, so getting back to our estrogen pathways, we've got to remember that 2-to-16-hydroxy ratio can be important in other diseases. oestrogen driven disorders but for us within breast cancer it's particularly important to look at the CYP1B1 or the 4-hydroxy oestrogen pathway because that's actually can be linked to direct DNA damage which is of course a significant problem for us. So when we get to our pre-regulated CYP1B1 and we'll talk about what that might be due to, we get to 4-hydroxy oestrogen and then we need to detoxify it because if we don't then it gets to make quinones, which can then bind to and damage DNA. And the way we would try and get rid of 4-hydroxyestrogens, we methylated via COMT. And then we also, when we get to the quinone pathways, we might want to have a look and detoxify those quinones via the GSDM1, GSDT1 enzymes, and also quenching if we radicals that are produced within that pathway with SOD. So this is really, again, the problem outlined in a bit more detail. You can see that we've got a few opportunities to detoxify those four hydroxyestrogens before they get down to the quinones, which can then form DNA adducts and cause DNA damage mutations and potentially contribute to the cancer formation. So it's really important for us to target the glutathione S transferase and COMT within this particular setting in particular. and balance it out with the CYP1B1 which can be upregulated due to a number of environmental pollutants. So if you're thinking about it, in terms of CYP1B1 inhibitors, we might want to look at resveratrol and trans-pterostilbene. And trans-pterostilbene is particularly useful because it doesn't inhibit COMT to the same extent that resveratrol does, and it also doesn't have as many upstream washing effects that resveratrol does as well. So resveratrol washes over the whole oestrogen pathway in quite a profound way. It can inhibit CYP17A1, do you remember those first few steps that make the androgens, and it can inhibit aromatization of testosterone to oestrogen and then further inhibit CYP1B1. So it does a number of things along that pathway, whereas transistors still being tends to have much more contained effects. And there are others such as epigenia and quercetin that have also been shown to have some effects on CYP1B1. But the really important thing for us to do is to assess what might be upregulated in CYP1B1. And it can be a genetic SNP contribution, but it would also be upregulated by inflammation, smoking, and exposure to polycyclic aromatic hydrocarbons, various environmental pollutants. And let's not forget that we need to balance phase one, phase two overall and support those downstream pathways. What's really interesting is that CYP1B1 may also play a role in angiogenesis. So you can see that you can actually set up this whole cascade via this one particular enzyme. So with COMT, it's important for us to provide sufficient methylation cofactors without overdoing it and very, very important to have magnesium. And it's also important to address potential increased viral mobility distress for people who might have a COMT SNP. And then maybe issues with specific supplements. They're usually most pronounced in homozygotes. So that's where the double variant is present. But this is early evidence. And some of these have been frequently seen in clinics. So that's resveratrol, quercetin, EGCG, methylated B12 sensitivity. And so just to be mindful of that, the fact that. You know, we do use them for specific reasons, but for people with a double COMT variant, that may not be particularly as helpful as there would be to others. Hence the need for always personalising care and not just chucking the same protocols at everyone. And when we're looking at trying to detoxify the quinones and get rid of them before they cause DNA damage, it's important for us to assess the the efficacy of the glutathione pathway and that's looking at your genetics so that's your GST-M1, GST-T1, there's a third isoform called GST-P1 as well that is slightly more relevant in other cancers and making sure that we also of course reduce toxic load overall anyway and the way we try and upregulate the glutathione S transferase enzymes is by ensuring adequate intake of cruciferous vegetables, particularly broccoli sprouts. And just as a reminder, please don't supplement any CO2 reactive treatment because some of the kill effects of some of these therapies may be reliant on generating some of those sufficient oxidative stress and also there is an aspect for where cancer cells might use these in a protective way and actually engender treatment resistance. So let's not do that. At the moment, what we need is we need more trials. We need to actually figure out what's dogma and what's actually true in terms of harm. But I would generally not do that during active treatment. But we can use normal food amounts of cruciferous vegetables to just generally support a number of different pathways, including and glutathione S transferase if there is a vulnerability there. And other points of interest, I thought it would be quite interesting to connect the androgens here to the oestrogens. Now, we know that oestrogen and progesterone have to be in balance because unopposed oestrogen is a significant problem. But what's interesting around androgens is actually the effects of androgens in breast cancer-dependent subtype. And androgen receptor expression in estrogen-positive breast cancers actually antagonizes the proliferation stimulation of estrogen receptor alpha and actually upregulates estrogen receptor beta to try and put the brakes on the system. So actually it might be beneficial for us to activate androgen receptor in these breast cancers. But in HER2, actually there is a synergy between androgen receptors in HER2 where you would result in significant stimulation of MYC. PI3K and ACT pathways, and that results in cell growth, proliferation and survival. So you can see why everything is context dependent. There isn't really one thing that our bodies don't work like this. We don't work, oh, we only have one response. We have a multitude of responses depending on context. And in triple negative breast cancer, the role of antigen receptors is controversial and slightly again context dependent. But there is some thought that low androgen receptor expression may be associated with better response to new adjuvant chemotherapy, for example. Prostate cancer. So just a few thoughts to say about that and just a reminder about it. And this is where the sort of more intricate aspects of testosterone versus DHT come in. As we talked about before, what's really important for us to think about is the fact that there are a number of ways in which. Yeah, testosterone function... Pathways can be affected by different metabolic factors. So as you remember, the free testosterone is the one that's not bound by SHBG. And as you also remember, the things that lower SHBG and create more free testosterone in the body are a number of things like obesity and insulin resistance. But the other thing we've got to remember, free testosterone is... probably not the harmful molecule in prostate cancer. We also want to look at testosterone being reduced by 5 alpha reductase to dihydrotestosterone DHT and then that binds to the androgen receptor, makes a couple, edimerizes it, and then it goes off and affects a number of target genes, including those involved in growth and survival. So what's really important to us is really it's more of the DHT drivers, but also the wider picture, because unlike breast cancer, it's probably not. as amazingly clear-cut from this is just a just you know testosterone issue i think there's a number of other things that are going on but looking at 5 alpha reductase specifically the one that converts testosterone to dht it's an increase by, guess what, insulin resistance and obesity. And here we go with the metabolic drivers again. And DHEA supplementation, which is why I personally think that's incredibly dangerous to have DHEA over the counter in the US where insulin resistance and obesity is rife. Fibrofloridactase may be decreased by things like sulfametho, beta-cytosterol, reishi, nettle root, pygeum. lipoxygenase metabolites of GLA and EPA and EGCG. And there are others. Of course, the list is not exhaustive, but some thoughts for you here. And it's really important for us to remember that metabolic health has a major role to play in prostate cancer. So you will see significant crossover with men with metabolic syndrome and prostate cancer. So that's something to keep in mind. And toxic exposures are also very, very relevant, particularly persistent organic pollutants and endocrine disrupting chemicals. And quite often they overlay in men with prostate cancer onto. SNPs that have issues with a detox pathway such as dsdp1 so something to watch out for and anything else from the systems review can come up as well but above are kind of the most common really metabolic drivers and the toxic exposure drivers with various associated SNPs as well Thyroid cancer, so I thought we'd talk quite specifically about that. It's the 20th most common cancer in the UK, on 17th for women actually, and it accounts for 1% of all new cancer cases in the UK. The peak is sort of in the 60s, but can be early in women, and women quite often rise in the 40s and 50s. And what's really important is the one cancer of which the incidence rates of which have increased by a significant amount over the last decade or two. And so it's really important that the incidence is rising. And what they're thinking is, of course, is there an overdiagnosis? And we talked about this before. Yes, there probably is. But there's also a genuine rise. And. in my mind we've got to think about the exposure to endocrine disrupting chemicals within that setting. And other key more conventional risk factors include radiation exposure, thyroiditis, that's autoimmune thyroid disease that results in active inflammation of the thyroid gland, not Non-autoimmune hyperthyroidism, for example. Family history of thyroid cancer and obesity. And symptoms of thyroid cancer can include a painless lump or swelling at the front of the neck. Although, of course, only one in 20 neck lumps are actually cancer. Swollen glands, unexplained hoarseness. It does not get better after a few weeks. So a throat that doesn't get better. And again, that is weeks and months. This isn't just a couple of weeks of the sore throat and other systemic symptoms and difficulty in swallowing that all need to be checked out by a GP. So four main types of thyroid cancer and other rare ones exist. And that's papillary carcinoma, which is the most common type and accounts for about eight in 10 cases. Usually affects people under 14, particularly women. And. and is Relatively easily treatable follicular carcinoma accounts for up to one in ten cases. It tends to affect the middle age, again, particularly women, and it's the one that may also be looked at via thyroglobulin markers, which we'll talk about in a second. Medullary thyroid carcinoma is quite rare, but it can run in families, which we'll talk about. And anaplastic thyroid carcinoma is the rarest and most serious type. and it's very very aggressive and it tends to rip through people very quickly. Papillary and follicular thyroid carcinomas tend to be easier to treat than the others which are much more aggressive. In terms of the drivers for thyroid cancers, they're most likely to be autoimmune or exposure related, so radiation, toxic exposure, and these need to be managed or brought under control where possible. You know, if someone's thyroid cancer may have been driven by their long-standing Hashimoto's thyroiditis, that control needs to be well established. And you need to unplug the drivers that might be driving autoimmune disease. Reduction of exposure is really essential and is primary because we want to do some support of healthy elimination eventually, but it has to be done extremely carefully, not during active treatment, because you don't want to overload the body. Modulatory thyroid carcinoma has an inherited component, and that's familial MTC and MEN2, which is a syndrome where they get multiple endocrine tumors, and there are some others as well. But remember that iodine is a double-edged sword in terms of risk. Now, iodine deficiency is a key risk factor for follicular thyroid carcinoma and possibly for anaplastic. But this is because when we are iodine deficient, ultimately we're not producing sufficient amounts of the T4 and T3 and we get the TSH rise. And the TSH keeps shouting at the thyroid gland to make more thyroid hormone. So this TSH ultimately can then lead to hypertrophy or proliferation and increase in size of the thyroid gland, which is why you can get those goiters with iodine deficiency. So it's important to say that this is really a big proliferation signal and a big sort of go signal to the thyroid gland. And this is why iodine deficiency is a significant problem. But iodine excess actually is also a problem because it might increase the risk of papillary thyroid cancer because it might stimulate thyroglobin antibodies. And my also act was more of a promoter. So with iodine, it is really important to not overdose or underdose on it. It needs to be the right amount. It's a bit of a Goldilocks zone here. And it's essential that we don't do crazy things with thyroid dosing either in terms of iodine. So for testing, we want to do a full thyroid profile with antibodies. And we want to look at nutrients and metals. So that's things like the ZRT labs profile. You might want to consider organic pollutants as appropriate to history. And that's things like the Great Plain Labs tests and consider genetics where relevant. Again, genetics will depend on what you're looking at. If you're looking at autoimmune disease, you might want to run something like a Life Code GX thyroid profile, for example. If you're much more concerned about the exposures driving thyroid cancer, you might want to look at the genetics. of doing the cancer genetics profile that I'm creating with DNA Live, or also looking at Life Code GX Detox Panel as well. So there are a number of things that you can look at. And this is really just a very, very quick overview. We can spend a lot of time on this and I will leave you some extra reading. But it's important to realize that there are a number of different classes of chemicals, including flame retardants, PCBs, phthalates, certain pesticides, all sorts of things that might be affecting. the risk of thyroid cancer, of course, other cancers as well, because the endocrine disrupting chemicals are not always that specific. So it's important for us to reduce toxic exposures in our clients with a cancer diagnosis really early on. So start getting them to work on their kitchens, their homes, their cosmetics, everything they can possibly look at to try and reduce their toxic exposures, because it's going to serve them well. In terms of diagnosis and treatment for thyroid cancer, diagnosis is done by an ultrasound with thyroid gland and FNA, which is fine needle aspiration where they stick a needle into the thyroid and aspirate a little bit of the sample and look at it under the microscope. But it's quite often inconclusive. And so thyroid nodules can be sent to a thyroid nodule clinic and have come up as. ultrasound inconclusive and far-needle aspiration inconclusive, which is tricky. There are more advanced genetic-based testing options available in the US, which we're looking at bringing over to the UK, and some private centres in London do run those. If we're looking at a well differentiated follicular thyroid carcinoma, then you can also look at blood thyroid lobe levels that might be significantly increased and also used for monitoring recurrence because it should go really low slash undetectable and if they start rising it means there's a recurrence. So if we've gone through ultrasound, final aspiration and we're in the stillness. and there might be aggressive features or family history, you would then be offered diagnostic hemifarodectomy and that means that half of your thigh would be removed and looked under the microscope to be able to diagnose it properly. And if the thyroid cancer is confirmed, then the treatment is usually total thyroidectomy, plus or minus radioactive remnant ablation with iodine, radioactive iodine. And with advanced disease or where there's BRAF mutations, they use thyroid cancer. targeted drugs as well, and there may be chemotherapy. So once you get advanced disease and things get a bit more complicated. But what's important to realize that following full thyroidectomy or TT, total thyroidectomy, the patients are usually treated with levothyroxine to complete TSH suppression. Because remember, TSH is a driver for thyroid. gland. So we need to completely suppress it. So you will see those patients come in and their TSH will be under 0.03. And then you think, oh my goodness, they're over replacing their levothyroxine. But no, that's the correct dosing for them because they had a history of thyroid cancer. And we do not want as much TSH around at all to be able to stimulate any proliferation of any other thyroid tissue elsewhere because there can be remnants of thyroid tissue. that might not have been removed. So it's important to know that if someone's had a total fibroidectomy, complete TSH suppression is the norm. And just a summary for us after this overview. So don't forget to assess and address the following aspects of hormonal balance, such as production, transport, sensitivity, and detoxification or hormone metabolism. And do consider the exposure extremely careful. So that includes radiation exposure, heavy metals and endocrine disrupting chemicals. Thank you for listening and watch out for some additional resources. ________________ 4.3 Metabolic and mitochondrial health approach to cancer and today we will be talking about metabolic and mitochondrial health and there's a second lecture in this series that covers more around cancer metabolism and special diets so the key aims within this particular system is really to reduce growth factor drivers such as normalizing insulin IGF-1 working with PA3K actin mtor pathways and um other aspects in terms of metabolism and balanced metabolism so autophagy mphagy glucose glutamine pathways varberg and reverse varberg effect as well so it's really important for us to remember that metabolic dysregulation plays a key part in a huge number of cancers um and the key aspects to that are things like obesity insulin resistance or diabetes and raised IGF-1 and meta-inflammation or metabolically driven inflammation is very very important so insulin actually from our perspective drives a number of things within the cancer process and it's just more than just affecting cancer metabolism so when we start going from a um it can affect the EMT transition so that's epithelial messenymal transition where the cell goes from being well adherent and close up to its neighbors and stationary to being able to transition to a more messenymal phenotype and being able to crawl into the circulation uh and that's because insulin can bind to the insulin receptor and activate the act and nfcappa b pathways and raz rafmeck irk pathways that will then go into um zeb twist and snail transcription factors and activate the this EMT transition so it's important for us to realize that insulin isn't just a growth driver or a metabolic driver it is absolutely also driving things like ENT angioenesis by again the razor map kynise pathway and cell motility as well as driving uh important enzymes within glycolysis and oxidative stress and um loss so the the way that insulin washes over the cancer cell is a number of different um hallmarks so something to keep in mind so obesity and cancer course there's a huge link between obesity and cancer and this is something that as nutritional therapists we can play a crucial role in helping people to manage with obesity there's number of aspects to it one is the fact that um we've got metabolically active um central adipost tissue which increases production of cytoines leptin releases free fatty acids and um upregulates other inflammatory markers and and those can then go into the cell and have direct or indirect effects um and the other things we've got to remember there's auto systemic physiology when someone is obese in terms of having higher insulin insulin resistance increased glucose free fatty acids and lipids circulating around um and it will also have higher estrogen which is really important for hormone driven cancers um as well as inflammation I've mentioned so with the direct effects in cancer cells um this kind of meta-inflammation environment promotes signaling pathways such as uh through insulin uh binding and IGF-1 binding to their receptors and activating various pathways estrogen binding to its receptors and then inflammatory cytoines inflammatory messengers activating jackatinfa B so you can see that actually we'll be driving a number of proliferation pathways will be driving more tumor inflammation having metabolic effects as well and there also indirect effects in the tumor micro environment where you can get cancer associated dibicides um and increase inflammatory cells and a much more pro-inflammatory tumor micro environment which as we know compromises a specific anti-tumor response and also can engender treatment resistance so it's essential that we try and get people to sort of normal waist height ratios and normal BMI for them igf-1 in cancer is important one of the reasons we talk about some dietary modifications and lifestyle modifications and IGF-1 um or insulin growth factor one can bind to its receptors and activate the same pathways that we've seen before so Raz Rafme pathway or you can see the PI3K act mtor pathway and these both result in proliferation increased protein synthesis and increased survival of cancer cells and what was really interesting is within breast cancer what they did a study in the UK bio bank and over 200,000 women and what they found is for um those in top 20% of high IGF concentrations patients had um an increased risk of developing breast cancer 1.2fold increase so what is interesting is they stratify these women and for every additional um five nanom moles per liter of IGF-1 the risk of breast cancer is increased by 1.05 so there is there is a link between IGF-1 and breast cancer is something that we definitely need to address the other things to mention is that IGF-1 can bind to IGF receptors and engender treatment resistance and you can see actually from this perspective there's a number of different cancers in which it can promote resistance including a resistance to and trustmab in breast cancer including um lung cancer um drugs as well and ovarian cancer and prostate cancer in terms of androgen deprivation therapy so it is an important aspect for us to look at there are some dietary factors that we can use in managing IGF-1 access and that includes um a low GL low GI diet a Mediterranean diet where they did a randomized control trial in bracka and show that a Mediterranean dietary intervention with moderate protein restriction was effective in reducing serum GF1 and also adjusting anthropometrics um that could also modulate breast cancer risk so protein restriction seems to be an important factor within IGF-1 and it's trying to stick to a max of 1.2 to 1.4 g per kilogram usually we want to uh as much as possible during active treatment trying to stick to a max of that um we might want to go lower if people are not having a lot of demand uh and we might want to go towards the higher end of 1.2 to 1.4 if people are having a lot of repair demands during active chemotherapy and radiotherapy and just postsurgery what's interesting is of course calorie restriction is another thing that reduces IGF-1 but it's not really a feasible strategy in humans uh when they did the trials they found that intake might need to be reduced by 50% plus and this is just not a feasible strategy to use long term fasting is another way of um of course managing IGF-1 and then number of different fasting regimes from an extended overnight fast of 13 hours plus to 168 TRF etc and dairy intake because that's really the reason why we think about dairy as an issue in um breast cancer and some of the other uh cancers are particularly IGF-1 driven including prostate because um actually what what has been found in several studies that you know increased milk intake interestingly not yogurt but milk intake in particular has been associated with increased IGF-1 concentration so ideally we want to try um and avoid it in in sort of IGF particularly IGF1 one driven cancers or small amounts of organic fermented because that has not shown an effect on IGF-1 levels um so this is something to keep in mind um and sometimes you know when when people are particularly wanting to keep their organic fermented dairy in and they are um they have an estrogen um positive breast cancer we can also take a look and at measuring their serum IGF-1 levels taking dairy out seeing what happens then and then putting dairy back in and seeing what happens because everybody is biochemically individual and we cannot assume that in every single person IGF-1 will be driven to the same extent by by dairy so this let's look at the PI3K actin mtor pathways that's activated by a number of things like you can see at the top that's insulin receptor and IGF-1 receptor when these receptors get activated you can get the activation of act which is a really key cynise it then activates a number of different downstream molecules you can see um such as foxo um MDM2 the ones that's actually involved in um apoptosis you can see a number of things that are involved in glucose uptake proliferation angioenesis growth and metabolism so it's a really key lynchpin um molecule for us to think about um and when we look at mtor that's one of the um again a key metabolic hub points for supporting basically growth this is its job mtor is a metabolic sensor that um wants us to proliferate and grow and therefore it activates things like Mick um which then result in increasing glutaminolysis and replenishment of TCA cycle metabolites which we'll look at a bit later activates here one alpha um activates um number of different pathways that result in increased protein nucleotide and lipid synthesis and of course this is essential for the cell to be able to grow enough to divide so it it is at a really key target pathway and counterregulator to mTor really isk and so the idea of those two particular molecules is when the nutrients are plentiful and you get the growth factor signaling the this signals to mTor that there is room and space to grow so when we activate that we activate all the synthetic pathways and the cell grows and divides ampk is the opposite when you have decreased energy and you this means that the um ATP can get depleted and you can get a rise in AMP to ATP ratio at that point this activates LKB1 um kynise and this then activates AMPK and ABK's job is really to inhibit the synthetic pathways so um it will inhibit fatty acid synthesis and activate oxidation it can directly inhibit cell growth by blocking m2 at multiple different levels and inducing a p-53 dependent cell cycle array so it's it's a really crucial checkpoint so what we want to do within the cancer setting is activate and inhibit mtor to try and um block some of the pathways that are involved in um growth and proliferation the other things to mention of course is that glucose is involved and glucose and insulin receptor signaling are not just involved in the metabolic driver pathways u but they're also involved in mitochondrial dysfunction so when we get excessive uh signal via the insulin receptor and excessive glucose uptake we can actually get um increased diasylc glycerol fatty coa um which can decrease beta oxidation in the mitochondria and uh reduce mitochondrial density and function so it's not good for us to have too much insulin and glucose circulating around it's actually uh toxic to our mitochondria indirectly via activating the wrong wrong cell signaling pathways and what's interesting within cancers is mitochondria undergo reprogramming um so they're not nonfunctional it's really important to to think that just because we're doing aerobic glycolysis in cancer we are over reliant on that mitochondria are not sitting there doing nothing we do still use them they're just reprogrammed to be more beneficial to cancer and the way that this is done is they actually have autoactivity of electron transport chain which is actually generated more mitochondrial u reactive oxygen species um and then promotes mutagenicity and increased oxidative stress we have a reprogrammed TCA cycle and so it's the crep cycle and that actually gets reprogrammed to promote energy production in synthetic pathways so you can then get citrate as a um key intermediate metabolite in producing fatty acids and steroids alpha ketoglutarate gets diverted to produce glutamate and other amino acids um sexinal coa can get diverted to pulfurins and hee and there are key things bypartate that that will make new amino acids and DNA building blocks such as purins and pyramidines so instead of being more of a um burning TCA cycle in terms of producing energy via oxidative phosphorilation it becomes a bit more adapted towards a synthetic TCA cycle which produces um a lot of biosynthetic intermediates and you can also get due due to the increased um production of reactive oxygen species you can get altered mitochondrial DNA because of DNA damage and this is potentially linked to tumorogenesis as well so when we look at this node what are the key aspects for us to consider during um the intake process uh what makes us highlight this node on someone's um systems approach to cancer model and this is where we really need to um have a look at medical history and family history looking at type 2 diabetes early cardiovascular disease PCOS looking at current medications um so are they on any particular medications that might promote insulin resistance um what's the nutrition like of course this is absolutely crucial are they on a typical standard American on the standard British diet highgl alcohol lots of sweet fat which is basically metabolically a mitochondrial um mitochondrially toxic um pro-inflammatory diet low antioxidant intake all of these will play in both into both metabolic health and mitochondrial health um and lifestyle are they sedentary that do they have a lack of regular physical activity chronic stress sleep deprivation all of these things are important because they can affect insulin um resistance so particularly with chronic stress and sleep deprivation upregulating cortisol production and as we know cortisol is intimately involved in insulin resistance we also look at anthropometrics such as BMI and waist to height ratio and recent blood test results to see if there's any evidence of insulin resistance dysipidemia or elevated inflammation so in terms of testing there's some basic bloods that um the you know GP or oncology teams can do in terms of looking at HB1C and fasting glucose and fasting lipids if you're able to get a blood draw then fasting glucose and fasting insulin are very useful to plug into the Homer IR model that can notify us of insulin resistance earlier than deterioration in HBO1C for example and inflammatory markers are very relevant because of course quite often metabolic syndrome um picture presents with um both dysipidemia dislycemia and elevated inflam inflammatory markers there might be specialist tests that might be used as needed such as IGF-1 but they can be quite expensive genetics does play a role so we do look at SNIPS so such as TCF7L2 which is the one that's particularly sensitive to grain intake and high carbohydrate intake we can look at p gamma um and that's sensitive in terms of high saturated fat intake promoting more insulin resistance and we can use a number of different uh DNA profiles i quite often use DNA health from DNA life via Nordic but um life code has similar snips as well and you might also want to monitor anthropometrics unless it's triggering to the client in terms of interventions foundations are always important yes we can talk about supplementation and we will but it is essential that we have the foundations in place because without strong foundations everything will fall down and you know what I'm going to say lowgl anti-inflammatory colorful high phytonutrient whole foodbased diet and moderate not high protein healthy anti-inflammatory fat balance with a focus on extra virgin olive oil avocado oil avocados nuts seeds small white oily fish limited amounts of organic fermented dairy if any may require a short period of anti-inflammatory ketogenic diet if very disregulated and again it's not always necessary is just an option if you feel someone is very metabolically tricky um avoidance of alcohol minimization or avoidance of refined sugar complete avoidance of artificial sweeteners and avoiding any fructose not in fresh fruit um so now with the dairy bit it I I I'd like to say I don't take all of my um clients off dairy i would suggest that usually within prostate and hormone driven um cancers it's much more relevant so um it's it's just important for us to keep in mind that that might not be an intervention for everyone overnight fasting a minimum of 13 hours and metabolically disregulated individuals you might want to use 168 sorry we dropped off there for a minute so overnight fasting it said minimum of 13 hours overnight fast in metabolically disregulated individuals you might want to use 168 timerestricted feeding manage sleep and stress with regard to cortisol and also cravings we do know that sleep deprived and stressed individuals have more cravings and therefore more likely to fall off the wagon and um reach for the cookie jar so it is really important that we manage the sleep and stress angle as well regular physical activity it's an excellent insulin sensitizer and promotes healthy mitochondrial function alongside fasting so it's an essential intervention to recommend uh for people to do safely and under the guidance of cancer exercise specialists where appropriate and healthy weight maintenance of course and decreasing abdominal and visceral fat they're not in and of themselves a goal they're kind of almost a result of the previous interventions so but it's important for us to keep that in mind and and help people appreciate that um actually abdominal visceral fat isn't dead fat it's a metabolically active tissue that generates a significant amount of metabolic stress um and inflammation in the body in terms of interventions that are more insulin directed now this is not an extensive list we can talk about it for a long time but I thought I would put down a few relevant things so bourberine chromium of course citrus bergamo omega-3 vitamin and cinnamon and green tea extract can all play a role in managing insulin sensitivity uh but note that bourberine long-term use at high doses can deplete the gut microbiome so as we know it's an antimicrobial so just be mindful of that because you might not want to do that for other reasons um and herbs there are a number of different herbs um quite often the herbs that are most often used within the cancer setting that also have an insulin um beneficial effect in the insulin access are things like panax ginseng and tulsy or holy basil and they're the most commonly used jimnma sylvester can be good for cravings but it does support more insulin release from the pancreas so I'd usually avoid it long term in cancer it can be quite good when you're trying to get someone off the high sweet fat diet and help them manage their cravings but I don't tend to use it long term um so in terms of interventions within the IGF-1 pathway um those are the few things that have been found um to help um what you've got to remember again these are largely cell/an animal studies so just be mindful of the fact that we can't overclaim what we do find is generally terms of reducing IGF-1 levels curcumin EGC gapenine genistine liibin all play a role um they will can also um reduce um IGF-1 receptor um binding so that's important and then the there are things that are downstream so IRS1 is um is an important signaling molecule that again gets inhibited by pretty similar things that you would see upstream which is nice for us the other um molecule that comes up quite a bit here is dial sulfide um so that's really the sulfur metabolites from the onion and garlic family uh which are particularly made when onion garlic is is chopped and left particularly garlic is left chopped and um before cooking for enough time to generate these compounds so um again another great role for the onion and garlic family here and natural activators so as you remember we want to activate EMPK to kind of put the brakes on cell um synthesis pathways in terms of um making more substrates for cellular growth um and these are things again you can see usual suspects reratroletin curcumin verber egc and then you can see a couple of others such as denicide um RG1 and uh the flavin in hispiduline so it's important for us to again remind ourselves there is there are common seams that run through it there are natural pi3k act mtor pathway inhibitors so again remember that umk is kind of the brakes on synthetic pathways and cell growth and proliferation and pi3k act and mtor are the gas so we want to try and get our foot off the gas pedal and that's you can see again very similar things you can see the dial sulfides uh ginger curcumin um ginseng parthenolide from feverfview honino from magnolia so a number of things that are pretty similar um and a few more here facquinone from black um cumin seed and uh andography from andographis respiratory ecgine epigenine indulic carbonyl sulforophane from cruciferous vegetables facetin lutiolin is um really important flavonoids and so a number of things that again have has come up again that also have an effect on PI3K actintor pathways um and there's a little diagram here now there's more than that that affects mitochondrial dysfunction but just to remind you that basically curcumin and respirator are also really important um mitochondrial rehabilitators in terms of reducing mitochondrial dysfunction So in summary for metabolic and mitochondrial health we need to assess metabolic status using history anthropometrics looking at waist height ratio BMI where appropriate keeping in mind that not for not not BMI is not appropriate for everybody um using testing in terms of blood tests or looking at snips and repeating to monitor if you're trying to impact insulin resistance or um metabolic syndrome nutrition lifestyle first always foundational and crucial um anti-inflammatory whole food low GL high phytonutrient diet moderate in protein so with some degree of protein restriction avoidance of acted fructose fructose is pretty much toxic for in terms of isolated high levels of fructose rather than fructose confined in fruit with flavonoids and fiber and other things that buffer its effects avoidance of refined sugar and alcohol minimizing dairy to organic ferment in small amounts or avoiding in very sensitive individuals fasting exercise stress sleep healthy weight and reduction of visceral adiposity as well and can you can consider supplementation of course as personalized to the individual just be aware of the limited evidence based and don't overstate this i know there's lot of overstating on kind of the whole how to staff cancer circuit but it is important that we are humans not cells um and we can while we can use things that impact multiple pathways things like curcumin resveratrol bourberine cruciferous vegetables and onion and garlic family vegetables and their metabolites but we've got to also not kind of overstate its effect on very specific tiny molecules because u we've got to remember that um it's the clinical effects that count actually um and there isn't as much research around some of these um you know there are obviously in in that party a number of things that are very well researched such as curcumin um but I don't want us to get bogged down in trying to do the how to starve cancer and just throwing a load of supplements in without paying any attention to nutrition lifestyle and the whole person thank you very much for listening ________________ 4.4 Cancer metabolism and special diets (part of Metabolic and mitochondrial health lesson) hello and welcome to the second lecture on the metabolic side and we're going to be talking about cancer metabolism and the relevance of special diets in cancer So in terms of the systems approach we're down here at the mitochondrial metabolic health So in normal metabolism we try and regulate um our buildup and breakdown pathways or the anabolic pathways which build the cell up and allow it to proliferate and catabolic the breakdown pathways We regulate the balance between these via the cells sensing nutrients and growth factors um and being able to adjust its metabolism via things like EMPK and mTor um pathways to be able to say okay we're in a growth pathway or we're in a shutdown and um try and conserve energy and uh break down pathway Unfortunately cancer then becomes autonomous in its growth and growth regardless of nutrient depletions and whether there is um a growth factor um sensing pathway And as we found out in the beginning of our sessions um cancer cells often have mutated components of the growth factor pathways to allow them to have an autonomy to grow no matter what's going on around them I think what's really useful to understand is that when we look at um the mitochondria it's important to realize that actually we can use a number of different cellular metabolites both um during normal cell metabolism and also during cancer cell metabolism I mean here you've got the glucose feeding in via glycolysis um in terms of making pyuvate and acetal coa and feeding into the TCA cycle fatty acids get broken down into acetal COA molecules and amino acids can come in at various points in the pathway as well So in terms of cancer metabolism we know that rapidly proliferating cells require both energy and different metabolic substrates for growth So the key changes that occur when we um go into cancer cell metabolism there's an elevated glucose uptake by the glut transporters and elevated glycolysis and aerobic glycolysis or the barberg effect um occurs not as a consequence of metabolic failure The mitochondria are not defective but it's actually a specific adaptation to the requirement to produce both energy and cell building blocks rapidly Cancer cells also have increased glutamine uptake and utilization and enhance lipid and nucleotide biosynthesis And do remember that cancer cells can use a whole variety of substrates for their growth So the concept of starving the cancer starts the person So we should instead be focusing on the macro level of supporting the whole person all their different physiological systems and unplugging the root cause drivers in the process as well as then looking at the micro level and personalized blockades according to up-to-ate molecular diagnostics that are personalized which is called precision oncology So it's about being able to function in both the macro and the micro level confidently and the and in a collaborative way because um as we know we need to collaborate with conventional oncology options So the key consequences of having an upregulated aerobic glycolysis and lactate production is we are producing ATP rapidly for energy which is um supplies the um energy requirements for the cancer cells We also need to remember there's a production of intermediates to make cell building blocks to support rapid proliferation because if we don't make building blocks the cell cannot divide and make copies of itself So there's also an adaptation to hypoxy and fluctuations in oxygen environment within the tumor So that's another consequence of this And through um LDH producing lactate we know there's an acid acidification of tumor micro environment and suppression of effective anti-tumor immune responses So there's a number of consequences of having the barber effect and lactate production So in terms of overview this is just um gives you a a quick idea or a simple idea of the energy metabolism of cancer cells You can see the glucose being um entering the cell by the gluts So the glucose transporters it then goes into aerobic glycolysis and it says plus minus oxygen because you know these cells can also um adopt anorobic glycolysis uh in the context of fluctuating oxygen environment within the center of the solid tumors And then within glycolysis you have several different ways of of um which which way the the um metabolites can go Of course the pyrovate can then go off and um into oxidative phosphorilation It can go off via LDH to lactate and then that would be the aerobic glycolysis that goes on in the cancer pathways and that lactate acidifies the tumor micro environment It can suppress the effective anti-tumor responses and actually what we've got to remember is glycolysis also provides the substrates for the biosynthetic pathways such as a pentos phosphate pathways and amino acid synthesis So as you can see it's not just about making energy actually it's also about adjusting the tumor micro environment and providing the building blocks the cells need to divide So this is a more expanded view of aerobic glycolysis and you don't need to know all of this I think it's important for us to just have an overview of the very different enzymes So if you read something in the literature that says oh it blocks PFK or phosphoprinise you know what step you're looking at um but we are really focusing on glucose being broken down to pyuvate and then pyuvate um goes off to make um lactate by LDH but also some of it we do know goes off to mitochondria and also can be converted to alanine as an amino acid So in terms of biosynthetic pathways we've got to remember that the the cancer cells are also metabolically adapted not just in the aerobic glycolysis way but they also adapted their mitochondria for them to become more biosynthetic in nature So instead of just focusing on energy metabolism which is normally what happens with oxidative phosphorulation the cancer cell mitochondria are much more focused on doing the building blocks And this is what you've got to remember The citrate can come out and make um number of intermediates for protein lipid synthesis The glycolysis itself as I mentioned um via the pentosphosphate pathways can provide biosynthetic intermediates for making nucleic acids as well as um providing um uh um intermediates for serene and glycine synthesis from three phosphoglycerate And we've got to also remember that lipids can be bio synthesized from the um uh glycolysis pathway as well So got to remember that actually the normal function of cell metabolism gets significantly subverted in cancer And the idea isn't just to generate ATP or energy rapidly through glycolysis but actually to subvert the whole metabolism to not only be about rapid energy generation but also to be about producing those building blocks supporting the cancer cells to divide as well as manipulating the tumor micro environment So it's a very clever system and is much more about than just about energy So this is again just another um example of various um places where things can enter or exit the cycle I'm not going to go into it in great detail because we talked about um the fact that it it is biosynthetically adapted The other thing when you talk about the glutamine metabolism in cancer and really it has um twofold um functions within cancer cells One is that actually it's important for us to replenish the TCA or the citric acid cycle intermediates and that's called anoplurosis because we want to within cancer the cancer cells want to produce metabolites for the biosynthetic reactions and provide ATP by oxidative phosphorilation which doesn't fully seize in cancer cells and we know even within the same tumor some cells will be metabolizing by oxidative phosphorilation sometimes and some cells will be engaging significant the barber effect and glutamine actually has an important role in maintaining the flux and the flow through the TCA cycle and plays a critical role in maintaining mitochondrial bionergetics So it's an essential pathway within cancer cells And in terms of the glucose metabolism in cancer um got to remember that the um we we've got the glucose coming in and via blood glad transporters and then as we discussed going into pyuid and lactate and the pyuvid can enter the TCA cycle as well And then we've got glutamine and glutamine enters via a different transporter called CT2 And then after transporting into cells glutamine is actually um converted to glutamate via glutaminases And they have two different isoforms um called GLS1 and GLS2 And then the glutamate can be further converted to alpha keglutrate Um and these metabolites can then provide by synthetic intermediate for the TCA cycle So you can see that if glutamate goes down the alpha ketogluterate pathway it can go off and drive and drive and drive that TCA cycle making more and more bu building blocks for the cancer cell to use to be able to proliferate The other place in which uh glutamine can go is it can actually go off and um contribute to glutathione synthesis And actually it's important to remember that glutathione syn synthesis can be upregulated within cancer cells as a protective mechanism because they're generating so many reactive oxygen species This is not the full extent of metabolic complexity and sorry about the misspelling but you've got to remember that this there's so much more to it and but you don't need to know everything about it I think the important thing is to understand that it isn't as simple as just starving one pathway or starving multiple pathways It's about um understanding that cancer cells have metabolic complexity and it is too simplistic to think that we're going to block a few pathways and that would be it Hunky dory But talking about a bit of pathway targeting you've got to remember again um as I said to you before that a number of these studies have been done in cells only with a few animal studies and this is not um supported at the moment with with human trials in vast majority of these substances So when we look at this we take it with a pinch of salt In terms of the glut transporters then we've got number of those medications and natural substances that can block those including reseratrol genist and epigenine silibin from milk thistle then we can go down the pathway you can see a number of places where things can be um worked on effectively um but again as I said just keep in mind the fact that um and it's not an extensive summary but keep in mind uh the fact that we are not going to be very precise about the number of different metabolic ways that we could also target tumors from the medication setting with things like thbone pyroate 2DG etc But again this is not something or DCA down at the PDK enzyme but this is out of scope for nutritional therapists Remember this is not something that you'd want to do and it's of license to use by doctors as well So it's um it's a much trickier environment than what's been portrayed out there The other things to remember is that you can also target fatty acid synthesis We've got to remember that cancer cells have to synthesize quite a lot of fatty acids because they need to make them for their membranes to be able to make dividing cells And here we can actually might be able to block fatty acid synthes using things like EGCG lutiolin queretin lignance oluropane and hydroxyrosol both from extravirgin olive oil Um so a number of ways of working on that as well But again this is not an extensive way of looking at it is just some suggestions and the key thing is not to overstate the importance of any one nutrient or anyone pathway and not to overstate the importance of metabolic blockade while because it's important to not lose the whole picture You can do whatever you like with tumor cell metabolism but if the immune environment is still significantly disregulating you don't have good specific anti-tumor response not going to go very far ultimately So with cancer stem cell metabolism is um again these are very this is very early research cell studies Please take with a pinch of salt and don't over rely or overstate the importance But we've got to think about the fact there are number of uh different substances that can potentially shift the cancer stem cell metabolism into um a different regulated state So we that would aim to um effectively decrease the number of activity of things like LDH and pentosphosphate pathways And from this the list really includes things like um soy and flavors such as genine libinine which we know about from milk thistle vitamin E but here I would cautioning you this isn't synthetic vitamin E this is tootryenos quite specifically EGCG extravirgin olive oil polyphenols as we saw in the previous slide for fatty acid synthes and the usual suspects respirrol kurcumin quetin there's also misetin graviola um some other compounds that are a little bit more specific specific as well So special diets there so many different special diets with in cancer but I've got um I've outlined a few most common things you might come across A ketogenic diet is one that's been significantly investigated and cancer must be anti-inflammatory not the American version fasting mimicking diet intermittent fasting and timerestricted feeding Protein restriction and various amino acid restrictions serene methionine There's also they're looking at ways of targeting asparagene metabolism as well There a number of things that are being looked at So there's some early research There's a an article that I posted for you where um there's a thought about can we can we synergize um with um specific treatments using special diets So what we do know is that PI3K inhibitors are very tricky because they they cause hypoglycemia raising blood glucose and therefore boosting insulin levels trying to reactivate the same pathway that you're trying to block with the drug and of course having significant metabolic consequences wider than that as we know from the insulin lecture So the idea of it is um that could we combine things like PH3K um inhibitors with ketogenic diet to regulate insulin and glucose levels so we can remain um with the blockade of the PI3K pathway Uh with breast cancer in terms of her too um there there's a thought that maybe you might be able to use a fasting mimicking diet to make the tumor cells more vulnerable to some of the therapy with colon cancer they're looking at p-53 mutants that can't easily make their own supply of serene and can you give people well can you give mice really in this case a serine-free diet to hinder cancer cell growth So my key caution with regard to all of these amino acid restriction whether it's methionine free or low methionine diet or serene free diets is that is they're just not realistic in humans Okay it's very it's easy to do them in in lab mice but you are not going to be able to achieve it out in the population setting for months at a time which is how long cancer treatment takes So we've got to take it with all with a bit of a pinch of salt and say okay hold on a second How is it practically possible but we do know the ketogenic diet and fasting mimicking diets are possible And actually our research should focus on that And if we're looking at trying to inhibit metabolism then actually we'll be better off from what the evidence says targeting things like glut glutaminase enzyme and things like methionase enzymes rather than just sitting there trying to fully restrict people because it has other unintended consequences if you restrict amino acids particularly the essential ones So as I kind of mentioned already very early on in research cell studies cannot be relied on They're just more general thoughts and so that you are aware of the research But this isn't ready to go into clinic and go "Right I'm blocking your cancer cell pathways." We're not there Whatever anybody else says um we need human research We need human research We need biomarkers We need to see exactly what impact we have and exactly what um particular treatments we can synergize with and as I said practical restricting seem as it can be very tough in real life um outside the research setting you know I can control um a mouse doing what it needs to do and the chow that it gets I don't think we can do that as much with humans out there the most practical regimes as I've highlighted to use at the moment are number one always get people to this bit first so baseline anti-inflammatory lowg high phytonutrient moderate protein whole foodbased diet Okay that's already plenty to work with for most people who will come and see you Then you might want to use things like anti-inflammatory ketogenic diet and timerestricted feeding quite comfortably um with anything like extended overnight fasting of 13 plus hours to 16 time restricted feeding particularly for metabolically compromised individuals Um and then the other things that you can use is you can use a fasting mimicking diet although the research can be a bit equivocical depending on what setting you use it in but it's expensive Um so we've got to remember that it's probably probably not quite as user friendly still quite a commercial exercise So to be honest from a practical level I tend to favor these three approaches the most Um but again fasting mimicking diet is definitely something to also watch And I know there've been um sharing of recipes um on the portal and the um on on the forum rather Um so yeah please do continue doing that because it is important that we try and make this as livable and as cost-effective for our clients as possible And thank you very much for listening ________________ 4.5 Methylation and Cancer Genomic Stability hello and welcome to our next lecture on the role of methylation and genomic stability in cancer so here we want to be talking about having a balanced methylation of the genome and good genomic stability and this really covers two aspects one is assessing and addressing DNA damage pathways and their relevance in cancer and that includes p-53 brack one 2 um and several others things like u mismatch repair mutations which are common in hncc or lynch syndrome and prevention of cancer really involves minimizing DNA damage by managing the exposone and supporting normal antioxidant pathways such as nerf two among others and treatment however actually may involve deliberately inhibiting a DNA repair pathway to support the kill effect so for example in BA 1 BA 2 cancers there's a defect in the double strand uh DNA break repair pathway and actually adding a path inhibitor to it um inhibits the second pathway the cell can over rely on and therefore achieve a synergistic kill effect so normally in prevention we aiming to support DNA repair pathways but actually within the treatment setting we don't want to oversupport them sometimes we actually want to inhibit them during the can conventional cancer treatment to achieve the effect that we want the other thing we need to be doing is looking at the role of epigenetic changes as one of the earliest and most comprehensive genomic aberrations that occurred during the process of carcinogenesis and that involves things like focal hyperthylation global hypomthilation um as well as histone changes as well so p-53 is really important to to for us to talk about it's the guardian of the genome um and it is one of the most commonly mutated genes in human cancers so normally in normal situation DNA damage can activate uh p-53 via a number of different sensors including ATM and check 2 um and when p-53 it exists in a normal human cell and it's not activated it has a very short halflife about 20 minutes so it turns around very quickly because it's bound to a protein called MDM2 which directs it for degradation so it's a little bit like as a body MDM2 goes off and just chucks p-53 down the drain effectively but actually when DNA damage occurs this interaction between MDN2 and P-53 changes and P-53 is able to dissociate from their body and is no longer degraded it can then go into the cell and activate number of um transcription of different genes that could have three different effects we could activate a temporary cell cycle arrest and that's quiescence the cell stops dividing temporarily and tries to repair the damage we could induce permanent cell cycle arrest and that's in essence whereby the cell is permanently in effectively a sleeping state and won't divide after that or if the DNA damage is bad enough we would trigger programmed cell death or aptosis so p-53 is actually a central monitor of internal stress and DNA damage directing the stress cell towards one of these three pathways and unsurprisingly when cancer gets generated we want to the cancer wants to interrupt that process it wants to carry on dividing so it doesn't want to go into quies essences in essence and it doesn't want to commit suicide bypoptosis so disrupting p-53 is one of the key um mechanism in terms of um carcinogenesis and progression so the thing that we need to think about is there are different ways in which B-53 can be disrupted in cancer and that can involve um specific p-53 inactivating mutations or it can involve silencing the gene via different mechanisms now what's interesting about p-53 is it doesn't just lose function so it doesn't just kind of lose the brakes on on the um system but actually can can gain a new roles due to mutations so as we talked about normally if you look on the side where p-53 is um um down the normal front um you can see that normally DNA damage activation of various genes such as in mech um hypoxia heat shock or any other stresses will cause p-53 to direct ourselves towards the cell cycle arrest scinessence of quiesence alpoptosis for example now on the other side when we've got the mutant p-53 Actually what that can do is it can accumulate in complexes with heat shock proteins and have a new function where actually it inhibits DNA repair might activate or inhibit different gene expression and inhibit autophagy and therefore cause transformation and metastasis activation as a part of the overall picture and so what's interesting about P mutant p-53 because p-53 functions as a tetrammer that's a unit of four to be able to bind to the DNA and activate uh transcription of different genes the mutant p-53 just having one or two mutants can have this massive effect even if there are some normal p-53 molecules left so it's really important for us to assess for mutant p-53 which we can do with liquid biopsies or tissue assays from the medical front and then potentially we can look into targeting that there are no approved drugs for targeting p-53 and cancer at the moment however we can look at some of the early research in potential impact of specific compounds on mutant p-53 now many of them have lots of uh small molecule um numbers effectively so they're not really relevant for us in nutritional therapy but I'd like to draw your attention to a couple of things one is role for statins here obviously this is not up to you because it's a medical drug but this is one mechanism by which statins may be helpful within cancer is by actually targeting mutant p-53 for degradation but there are also some nutritional bits that we can look at here and that's capsasian which we know is found in chili peppers and PITC which is a compound found in cruciferous veget particularly rich in water crest and actually what's interesting about P EITC it actually can transform mutant p-53 into wild type p-53 and reactivate the pathways that that um that have been inhibited by mutant p-53 so this is really interesting and quite often we probably want to try and do both we want to try try and target it for degradation and potentially also try and convert as much to wild type P53 as possible so here's to water crest salad with a bit of chili so the other things to say to you guys is just a quick repetition of what I mentioned earlier is that DNA repair pathways are actually um we actually want to put pressure on them during active cancer treatment so this is just to mention the fact that we don't want to be sitting there actively supporting lots of DNA repair when we're doing active cancer treatment we're actually relying on many chemotherapies such as platinum chemotherapies as well as PAP inhibitors to actually induce DNA um damage within cancer cells and for them to be compromised to such a degree that they die so this is really important to remember so the other thing we need to think about is really the epigenetics and that's the regulation of gene expression via methylation and histone modification and here we're talking about specifically about um DNA methylation at CPG um points and also histone modification of the histone code where you can get acetilation of lysines and methylation the different residues on the histone tails that govern just how compressed the chromatin is um and how accessible the genetic code is for transcription factors to bind to in initiate or suppress the different um uh transcription of different genes so the key methylation changes in cancer within the genomic DNA are focal hypermethylation so it's too much methylation CPG islands that are normally protected from that and here DNMTsis DNA methyl transferase plays a key role and there's also global hypomthilation so what's interesting about is of course methylating things at CPG islands can um actually silence tumor suppressor genes without having to mutate them so that's another mechanism where cancer can get very clever and silencing genes that normally uh play a key role in regulating and um containing any abnormal cellular growth or DNA damage and this this is just a few examples where um different pathways might be affected by this kind of hypermethylation and you can see it covers a number of different pathways from cell cycle control to aptosis DNA damage repair and cell adhesion migration what's also interesting is there can be cross talk between metabolic side um things like IDH mutations and um the DNA um regulation via epigenetics so what's interesting is um in leukemias there can be Idh1 mutations and IDH is isocetry dehydrogenase and actually because of um there is excessive D2HG produced because of this mutation it can actually inhibit alpha keto dependent reactions and result in increased histone methylation increased DNA methylation and impaired cell differentiation so metabolic mutation can actually have a knock-on effect on how we regulate DNA expressions this is why it's really important for us to all to think about systems and really not hyperfocusing on any one thing to a significant degree it's really important to see the whole picture because it all talks to each other anyway so other pathways involved in gene expression regulations involve histones in terms of epigenetics and the histone code and it's histone code is quite complicated depending on which particular amino acid you might mealate it might activate gene transcription or repress it for example so the two main um modifications we might do to histone tails and that's lysin acetilation so um hats that's histone acetal transferases acetylate key amino acids and that promotes accessibility of the chromatin the genetic material and gene expression so they're kind of the writers they acetilate they tag those he histone tails and H tags or histone deacit lasacers they are erasers they remove the acetilation resulting in repression of the transcription of those genes and HD decks can be overexpressed in cancers and therefore are a target in terms of pharmaceutical development for age deck inhibition and there can also be methylation of histone tails may be activating or inactivating depending on location and these are done by histone methile transferases and demethylaces so age dioxin cancer really play a massive role in a number of different hallmarks that are highlighted here from cell differentiation and proliferation to metastasis angioenesis apoptasis cell cycle and inflammation the tumor micro environment so let's have a think about um some of the studies that might have been done on natural compounds within the setting and again I just caution the fact that this these are mostly cell studies with some animal studies so please just take it with a pinch of salt we can't say that there is evidence these are going to be clinically effective in humans but these are something to consider in terms of um overall effect so natural DNA methile transferase inhibitors are things like EGCG curcumin parthenol from feverfview queretin resveratrol genistine sulforophane and what's really interesting is that when you combine sulforophane within a from ashvagandha or withania you can get a synergistic effect ag which is a boswellic acid from boswellia serat frankincense and antroquinol d which comes comes from antrodia conferatum mushroom natural age deck inhibitors we that's where we can see cruciferous and onion and garlic family really shine with dial dulfide compounds and sulforophane playing a key role in nature inhibition acid as we talked about particularly rich in rosemary and tulsy but can also be found in blueberries apple peels olive and cranberries kurcumin seems to do everything so here we go again and butrin colon cancer cells so actually that's is something that I do use with my colctile cancer patients for a number of different reasons so just as a summary basically when we look at this particular um system when we're looking at um genomic stability and epigenetic regulation ideally in terms of prevention we want to avoid excessive exposure may damage DNA and support adequate repair um and then actually when we want to achieve a tumor kill effect during treatment the conventional therapies might actually be inclined to specifically target and impair DNA repair to achieve a tumor kill effect and this is your pop inhibitors and bracken mutant cancers for example epigenetic regulations of course the key changes you've got remember at DNA level are focal hyperthylation invol that is involved in silencing of key genes and global hypomthilation and then DNMT one of the targets um because it methylates um key CPG um sequences and then histone acetylation methylation also often disrupted and age or histone deacetylases are uh common targets currently for drug development thank you very much for listening ________________ 4.6 Bonus material from the Hormone GATeway course and today we're going to be covering estrogen progesterone and testosterone related dysfunction patterns and some of the management approaches so here are some of the possible scenarios we might encounter when we do some of the testing um and we might see uh estrogen to progesterone ratio problems uh or whether without low latal progesterone might see imbalances in phase one estrogen detoxification such as an abnormal 2 to6 ratio or elevations in full hydroxy estrogen metabolites and this may or may not be accompanied by poor methylation which is a topic in and of itself and the methylation side of things isn't going to be covered in detail here it's the usual interventions might want to see E1 E2 E3 imbalances which is um for example due to high E1 or low high E3 compared to the others um which is way out of proportion that normally needs looking at and addressing and parameopause with decreasing or low estrogen and progesterone or just estrogen or just progesterone because um it can present with a number of different patterns and they require different approaches as well as frank menopause with or without low testosterone brain so this is a clinical pattern where you can see there's a significant estrogen dominance or estrogen to progesterone ratio imbalance where the estradile is very much at the top end of the spectrum and is actually blowing past the normal range and the progesterone metabolites are lower end of the spectrum um and actually we would usually in someone like this I'd want to run a day 21 or so lutface progesterone to see if there's actual ovulation happening um this is likely to be um probably a borderline um progesterone so probably serum would be looking at about 30 35 something along those lines um uh and here you can see actually then the absolute progesterone on the other side is in postmenopausal closer towards postmenopausal range but there's still estradile within the normal range and that's quite typical really from parmenopause and again that sort of results um in um us kind of losing that lutal face progesterone you can get some cycle shortening or the cycle related abnormalities so in terms of the general overview of approaches if you have you know an abnormal estrogen to progesterone ratio or estrogen dominance we need to look overall at PTSD um and production transport sensitivity or interaction with other hormones endtoxification to actually understand the different drivers and target support so for example if you have estrogen dominance in someone who's maybe um obese or overweight and may have high alcohol intake you know there's going to be excessive production of estradile which you need to be addressing through management of lifestyle um and weight management there may be excessive inhibiypatic recirculation with digorin day secondary to dispiosis and again you would want to pick that up on history plus minus tool testing if someone is excessively aromatizing from testosterone to estrogen and you'll see actually testosterone is normal or low end of normal or low but there's plenty of estradiol around you might want to consider compounds with aromatase inhibitor activity such as reseratrol which is usually dosed at 75 to 125 migs BD BD is twice daily and cryin another name for which is 57 dihydroxy flavone and that's normally dosed 500 mg once or twice daily and an example example is gerro highdosese melatonia is also an aromatase inhibitor but it's much more used within the cancer setting really poor lutil phase progesterone you definitely want to assess and address causes for an ovulation such as PCOS for example and you might want to give some specific lutil phase support which is um would include things like vitex agnus castus or chastry uh usually thousand milligs in the morning and the morning dosing is important usually first thing uh you may consider vitamin C 500 milligs two or three times daily with boflavonoids and an acupuncture referral from the TCM perspective or ovulation support and it is important to be aware of the fact that just because someone does acupuncture they may or may not do the right acupuncture and if you want to look at ovulation support or fertility or women's health you'd want to look at someone who practices the TCM approach and who has experience in women's health of course then um other clinical patterns we might look at is that phase one estrogen metabolites you you might have the 2 to6 ratio that's inappropriately depressed so low to hydroxy high 16 or you might have high four hydroxy as you see here you know 15% is well above the reference range here and if you want to look at improving 2 to6 ratio you've got to remember that actually you might have normal 2 to6 ratio people who are relatively toxic still but that's because C1A1 which is responsible for two hydroxyestrogen metabolite production may actually be induced by polycyclic aromatic hydrocarbons so pollutants in smoking so in smokers and people who have significant toxic exposure you might have normal 2 to6 ratio but you usually will be pushing the four hydroxyestrogen metabolites um and you might want to also assess the causes for poor 2 to6 balance such as alcohol endocrine disrupting chemicals or contraceptive pill etc um and that's mainly long-term use of all contraceptive pill we don't usually use Dutch when someone is on that but actually as they come off it and their cycle start normalizing they might have quite a poor 2 to 16 imbalance key simple lifestyle interventions that you can use that absolutely do work is 2 tablespoons of mil organic flax seed daily and regular exercise and there are trials which are noted here there was a study in 99 post-menopausal women who consumed 2 tablespoons of flax versus controls for 7 weeks and showed improvement in serum to hydroxyone and 2 to6 um hydroxyone ratio and for healthy premenopausal exercises who were exercising 30 minutes five times a week which is a recommended aerobic exercise amount according to government guidelines you can see the 2 to6 ratio increase significantly um for the non-Ntes um you might consider DIM supplementation is needed and usually it's dosed at around 150 mg BD for bio response DIM well it's really important to be aware of the fact that DIM can actually upregulate not just cip 1 A1 activity but CP 1 B1 as well in a proportion of susceptible individuals and particularly those who um already have C1 B1 upregulated snips so there was one interesting trial in 98 when nammoxifen that were dosed at 150 mgs BD for bio response in that showed an increase of 2 to6 alpha hydroxyestrone ratio but also decreased indoin effects which is the active metabolite of tmoxifen and they were unsure whe as to whether that would lead to an impairment of clinical efficacy so I am very cautious with DIM as a clinician because I do treat a lot of very complex individuals and I also um look after women with breast cancer so I would we sometimes automatically go for um the supplementation in cases like this but actually if we look at causes for poor to 16 ratio and do some simple interventions most of the time it will normalize without having to do extensive supplementation with zip 1 B1 we're looking at managing the four hydroxyestrogen metabolites and there it's important to look at influences that might be upregulating zip B1 such as Gnaps um and also xenobiotic inducers so that's various pollutants such as dioxins and pesticides and polycyclic aromatic hydrocarbons which can actually induce expression of CON B1 through the signaling via the aerrol hydrocarbon receptor and it's important to realize that CON B1 doesn't just do for hydroxyestrogen metabolites it can also activate procarinogens by hydroxilation so increased B1 activity is always managed in the clinical setting from my perspective because it's procarinogenic so even if someone who might have C1B1 snips in a previous elevated four hydroxy is now on estrogen suppressing medication such as in case of breast cancer I will still look after this enzyme because the other jobs that it does including very many things in terms of being involved in um uh retinoid metabolism and melatonin metabolism and other things and what's interesting is actually when we have the uh activation of um C1 B1 expression by zenobiotics we can have hisperitin which is derived in the body from hesperodine um inhibiting this activation so again sometimes that might be considered for protective measures as well as of course the most important bit is turning off the tap which is reducing exposure there's some key C1B on inhibitors that you might want to consider in clinical practice respirator you know around about you know 100 to 150 milligrams in divided doses in the number of different people on the market who do it time health is probably the most cost effective we want transferres feratrol uh pure encapsulation there are other um manufacturers transfer still bean or TP for short because it's quite a long thing to pronounce um is usually dosed at 50 migs once or twice daily and jerro is the most common brand used it's best used in people who have double compared to resveratrol because reserrol can be a bit of a comp inhibitor in susceptible individuals um so I tend to use it um in those as to not affect methylation as well so if you see someone who's um on rveratrol um who might be having beautiful um four hydroxyestrogen but they are low methylators you might want to be careful and switch them to TP um other sources that I have um less really clinical experience with tendin to use the first two the most are dietary supplemental sources of ramnitin such as yellow red onions because and they're also a source of quetin of course and ginkaoba but I do tend to use it in slightly different settings so the first two I have to say consistently deliver the results that are measurable from the Dutch perspective and that's just a reminder on the fact that C1 B1 isn't just um a four hydroxy estroone producer it's involved not only in steroid metabolism a fatty acid metabolism vitamin A metabolism melatonin metabolism and upregulation of C1 B1 uh can not only contribute to cancer but also fatty liver obesity metabolic diseases and other um aspects so it is an important enzyme to know and manage and this is just an example of a clinical effect i have many dutches that show this but I thought that's that's quite dramatic so I wanted to show you this this is a in a person with um metastatic estrogen positive breast cancer unfortunately her integrative practitioner seemed to think that this did not require managing and she was progressing quite significantly on on third line therapy at that point um and you can see her full hydroxy was a 68% um and after 50 migs of TP for 6 months it went down to 17% and then we added another 50 mg and I'm expecting the results any day but we usually see between 50 to 100 mg and normalization of all hydroxy um relatively quickly within a couple of months we always need to remember that the beyond this we need to think about the gut microbiome and betaglucaronidase um deconjugating the um uh estrogen we're trying to excrete and uh sending it back into entrahypotic circulation so if you see elevated betaronidase on stool testing and you've got someone who's clinically really pushing their estrogen levels and you can't identify any other sources for why they would be doing so um you definitely need to address this and managing dispiosis is the most important you must manage the root cause no matter how much betagluconius inhibition you're going to be doing you need to manage the root cause so you don't have to continue supplementing them so it's quite often ecoli driven dispiosis but there are other bacterial species involved as well such as clustian peragens and bacteridous species and we see a lot of bactidus overgrowth um in clinic for nonMTS you might consider calcium dlucarates the 250 mgs VDOT TDDS um and then as I said while you're managing the root cause and other flavonoids also can be quite useful betronis inhibitors and can be used in nutritional therapy setting so lutolinquetin scatilarian which the latter comes from bol skull cap or scatilaria balences of hangin in um Chinese medicine and there are a number of different lutonian food sources such as celery parsley thyme chamomile which is also rich in epigenian chrysanthemum tea which has been used in traditional Chinese medicine for a very long time so there's some options for you here and the other patterns might be involving um E1 or E3 being way out of proportion to E2 so you can see here here in the in the top example E1 is significantly elevated where E2 is in normal range and E3 is actually bottom end of normal so there's something really pushing that E1 um and then on the bottom side you can see that um actually this woman is in menopausal range for E1 E2 but her E3 is significantly elevated and to be honest when it's elevated this much it's usually there on each trial being given to them so they're actually being given E3 in some form or another but you will see less dramatic elevations for other sources so if there's high E1 it's mainly driven by adipose tissue E1 production so often weight loss is crucial here and it's an important thing to address where there's um low E3 you need to look for and remove CIP3 A4 inhibitors and and there are many of them around and you can look up various list but most common are grapefruit and golden seal a number of different medications so always always if your E3 is out of proportion look at CI 3A4 look at the medication list and see if you can spot any drivers so same goes for if you have high E3 and you need to look for C34 inducers so for example St john's W and number of other medications including steroids and you might then also consider not only removing them if that is possible but also potentially adding CIP 3A4 inhibitors if that is clinically indicated so clinical pattern 4 is just an example of permenopause with decreasing um and low estrogen progesterone so you can see here you've got very much sort of borderline low progesterone metabolites and the same goes for um estradi very very typical pattern and there those two are going down together and this is really frank menopause with possibly low testosterone the reason I say possibly because of course we need to check whether someone is actually excreting testosterone in the urine i would always run a blood um free androgen index really so total testosterone SHBG free testosterone FAI to just check where that testosterone is um and this is parameopause again most of the time we get told that the progesterone drops first but they're definitely parameopause or women have normal progesterone now definitely ovulating but actually their estradile is starting to drop a bit and they're starting to experience some of the estrogen deficiency symptoms so it's important not to assume that you know what's going on in parmenopause i'm going to mention resveratrol here and it's going to come up later on um in management but um in the menopause section but it is well evidence menopause support with randomized control trials and the dose uses mainly 75 mg twice daily or BD with actually long-term use were very well documented of 24 months plus shown to be safe and it's shown to improve overall cognitive performance attenuating the decline in the cerebravascular the reactivity to different stimuli reduction of fasting glucose fasting insulin insulin resistance and we know that that's a major problem in menopause actually women are becoming more insulin resistant pushing their cortisol as well as improving sematic menopausal symptoms general well-being and what's interesting about respirator it's also a potential chemreventive agent of breast cancer and I've got a question mark here because we need to prove it but in terms of the mechanism of action it's really quite interesting and you've got to think of respirator as washing over um a number of different enzymes in the steroidenic pathway so actually um it can slightly inhibit the sept 17A upstream it's neuromatase inhibitor um but it can also inhibit comp a little bit in susceptible individuals so just be mindful of that when you're looking at that as a potential intervention um and it it is effective across um a number of different symptom presentations in menopause so just a quick self test um have a little pause of the video have a look at these test results summarize the picture here what is going on with this lady and what needs support um and make yourself up a little mini mini lifestyle and supplement um/medation plan if you're a prescriber and see what you think okay I'm going to move on to testosterone patterns in women now so this is a typical pattern of high androgens in women with a significant file alpha preference um so you can see there's elevated testosterone not just the other androgens as well and you can see what's interesting about it is you can see elevated normal testosterone and sometimes with a significant file alpha preference you need to have a think about it so if we're managing high testosterone we must consider the driver such as insulin resistance might need to consider the cip 17a snips and uh doing some upstream inhibition for example with epigenian and usually use onen at 50 mg twice daily because that's a brand most easily available in the UK and in the US we have uh far more options if we looking at high five for reductase activity we might want to consider green tea as a dietary intervention has got a very gentle five alpha reductase um inhibition via EGCG alongside supplementation with one or two agents from uh choice of red ratio zinc at 15 to 30 migs nettle wood so meta betytosterol there are other lists but these are the ones that I find most useful clinically and you can find a number of combined formula so uh on Amriita does one with sopame and nettle root and number of other So it's quite useful to look for combined agents um rather than trying to do individual supplementation in this case and of course low testosterone is really common in women as well and we're seeing women drop their testosterone and parameopause and menopause quite significantly um of course if you're a medic you have an option of transermal testosterone but it's really important that we don't just chuck medications in people that run away um we really must have the long-term view of the fact that women need to be able to make age appropriate amounts of testosterone throughout their lifetime actually testosterone production does not depend on ovarian function in post-menopausal women and we can get normal levels and we should be optimizing natural production with the strategies outlined below and looking at HP access support quite often the people who tend to drop their testosterone levels in parmenopause are not sleeping well have poor vitamin D status and are stressed out of their mind and that's usually the pattern that I would see um with someone with low testosterone and the various variations on that so it's really important to optimize sleep sleep has an effect on testosterone in males and females and it's essential to get that sorted vitamin D levels need to be optimized regular weight training um there's lots of support on that in terms of evidence and the usual recommendations to full body strength training sessions twice a week or can be split into shorter chunks you might consider tribulous terrestries as a supplementation or libe care um in terms of supporting testosterone levels and libido but the quality really does matter so with tribulus there's lots and lots of uh supplements that are low cost and low quality um so somewhere who actually tests their supplements or has standardized extracts is preferred somewhere like Time Health for example there's a few notes on SHBG management if you have low free testosterone high SHBG and you want to lower SHBG a little bit you might want to consider 10 milligrams of boron once one to four times daily i tend to go for twice daily and see how we go and reme-measure SHBG and testosterone and free testosterone but it's really important when we're lowering SHBG to remember this will impact free estrogen as well so then it may or may not be desirable depending on the clinical situation quite often we also see low HPG this is much more common in insulin resistant hypothyroidism states and that increases free estrogen and testosterone so quite often that will cause that picture of estrogen dominance or estrogen to progesterone ratio being poor um and that needs addressing so you need to address and target insulin resistance hypothyroidism they need to be optimized normalized and SHBG can also be addressed through a low-fat pescatarian or vegetarian high fiber low moderate protein diet and or weight loss is appropriate and there's some examples of combined patterns you know PCOS being one of the typical things where a number of things go wrong at the same time so you can see here this lady is pushing testosterone she's got she's hyper androgenic she is pushing testosterone which is pushing the um other androgen metabolites and as well as looking at um you we're looking at definitely at estrogen to progesterone ratio imbalance here with high E1 high E2 um and borderline um sort of borderline low on the some of the uh progesterone metabolites um and again depending on the serum level we'll see that she will probably have some ovulatory cycles some unovary cycles so that's an important one um and again you will quite often see um relatively dramatic results with uncontrolled PCOS so here you can see an SHPG of 15 which definitely needs addressing and actually the total testosterone is not out of range so the only problem with this lady is not that she's producing too much testosterone this is a different person in the serum but that she's absolutely pushing free testosterone because her testosterone SHPG ratio is significantly elevated because SHBG is ridiculously low and that needs addressing so increasing fiber looking after um um any correcting any insulin resistance and um hypothyroid etc makes a big difference and you can see this woman is um got a fasting insulin that's significantly elevated um so just as a summary and we'll address PCOS in a different lecture but I just want to show you some how some of these combined patterns play uh come into play and my summary is people not protocols look at the pattern not just the condition you know we're looking at precision health or precision nutrition here we are not trying to say this is my protocol for PMS or PCOS and I do it regardless of what's going on we need to use targeted tools and this is what ultimately this course aims to provide you with do consider the big picture not just what's wrong in the Dutch right now and how to correct it but actually what is driving this why is this being created isn't insulin resistance upstream is there toxic exposures that might be driving it is there stress what what is going on here what's actually driving the imbalance and we need to not only correct the imbalance but correct the drivers and address the root cause well thank you for listening here are a few references and I'll see you in the next lecture. Month 4 Q& A Session What do we think? What do we think in general? Go on, let's do some group think. What would you do in your practice? You've got something that interacts with chemo. What would you do? I won't give it with chemo. Yeah, just don't give it. Don't give it. And you know what? People are so obsessed with single agents like berberine or even curcumin or whatever it is. And I'm like, actually, there's always a way of trying to figure out of how to get yourself benefits without having to use something that interacts. so you know there will be the big hitters that you'll always hear about but there's always a way around it so depending on what action of burberry you're looking for in that particular patient you can probably find other ways of getting that anyway in a way that doesn't interact i think that is important so don't risk it the last thing you want to do is to either increase toxicity of chemotherapy or inhibit it enough that it doesn't have the desired effect so if something interacts to a moderate degree okay or a major degree with chemotherapy and then we really should not be using it so i think that's that's hopefully a reasonably easy question um we'll do the case related questions last but i am going to quickly reshare my screen so we'll do some of the other questions in a sec so uh we'll do becky's question about a a long a mini essay i should say from becky or one of those i thought i just i was doing it doing that thing was like over explaining myself you know that was like i almost had a brain fart which is fine which is why we love those as well so i think it was it was really just i think more of a discussion around number one tolerance and that they think there's any there's any evidence actually from the tolerance perspective that we have in the vast majority of supplements so It's very different to certain things like drugs that will over bind to receptors, will cause receptor down regulation. Most natural substances, you will find that because they're pan pathway, they don't act on a single pathway. It's not giving you a single drug that acts on a selective for 80% of the specific receptor, which will cause receptor down regulation and tolerance. So medication tolerance is quite well known. Like we know about it, we know when that happens. It's very, very different. So I've never seen any good evidence to show me that there is good tolerance. Now you might choose to rotate it for different reasons, for whatever reason, you might choose to rotate it according to things, according to cycle or according to your symptoms or according to vitamin and other things. But I don't think there is any good evidence for tolerance development to things like curcumin, for example. So I haven't seen anything that's out of the chain. I'm very happy to be corrected. So if you've seen something that I haven't seen, please let me know because guess what? Nobody can keep up with the whole literature. No, and it's just, I think it's, there's not really enough on this. And, but I was just, I suppose, thinking you have tolerance in caffeine, you have tolerance in alcohol, you have tolerance in other sorts of drugs, you know, and I was sort of thinking about, but also I was kind of thinking about the body goes through a lot. And I think we underestimate because on one hand we want to say, oh, don't worry, these natural products are nice and safe. Oh, you know, but, um, It's when it suits us, we almost it's that sort of cognitive bias, whereas you could be adding and adding and adding and adding and adding. And the body then is going through so much. I'm like, I think we need to think about this because it's about nurturing the body and not treating cancer. Right. So I'm sort of thinking about that pause and resting and tolerance. And it's like almost the art versus the science of nurturing the body. I agree. And I think there's definitely an over-supplementation approach that you will see a lot of. For people who've done a lot of research, they've gone on to various websites or books and then they come to you with 20 supplements. You're going, okay, well, half this stuff interacts with your drugs. Half this stuff is actually not suitable in your case anyway because you've got these particular blood test results or these functional test results or whatever it is. So I think it's important for us to be mindful of that. I think the caffeine and alcohol tolerance work because it's a very specific mechanism for them. You could remember that with alcohol, there is a specific upregulation that happens. There's a consequence. Your body has a mechanism for adaptation, same for some of the drugs as well. So alcohol is a drug ultimately, and it has a drug-related tolerance to it. So opiates will have a tolerance to it. And I just haven't seen the same evidence for pan pathway natural substances. And that's why I'm cautious in applying the same kind of mentality. But equally, you know, you might find that you do it for different reasons. So obviously, there will be times when I will discontinue supplements because somebody's going through surgery. I always change my supplements, frankly, for most of my patients, because I always give them a dynamic plan. So the idea is that we'll dynamically monitor where they're at in the stage of treatment, what their biomarkers are, what their side effects are, what their MSG is. I mean, about a million things. And based on that, we will decide how to modify their supplement plan. So I kind of feel like for me, dynamic adjustment is built in less from point of view of tolerance as an approach, but more from point of view of dynamic adjustment to the person and their needs and their treatment. Does that make sense? Yes, it does. Thank you. And then yeah, Facetion has actually had this more of a heyday in the last couple of years from the research perspective. So yes, I mean, to be on a CSC compound targeting, it's going to be like a four-page list. And that's even with things to do with the best evidence. But Facetion is interesting. I don't actually take this analytic approach consciously. I will... It will very much depend, again, on the individual basis. I will look at where somebody is at. So are they maybe post-radio? Are they post-chemo? Are they post-chemo immunotherapy? And then my approach will change that. What is the residual toxicity? What is the ongoing treatment plan and prognosis? What do I have to watch in terms of late effects? because the other thing we've got to remember is a lot of those therapies can have late effects and we need to monitor them. What's the current biochemistry and haematology looking like? What is the patient feeling? How else, like you talked about that whole body and nurturing the body, how else is the body feeling right now? You know, most people come out of treatment and if we're thinking about, you know, more of the post-treatment approach, You know, the HPX would be dysregulated. They might have had significant oxidative stress. There might still be a little bit of inflamed post-treatment. So mopping that sort of thing up according to what's going on with the person is important. So I use Fasetian in specific cases. in specific context, but not consciously as a senility because there's not a lot of data on conscious analytic approaches within post cancer recovery. So there's loads and longevity space, loads and loads of longevity space. We've got to remember we're not in longevity research. We can't apply longevity research necessarily post cancer recovery. So I think this is an active area to watch in terms of risk. It's already significantly increased just for the last past couple of years. But I would like to see more evidence on that. Say, you know, talk about autophagy. You know, there is the balance between that and cancer. You can't do the same thing in longevity because actually it's not as straightforward balance within the cancer setting. So cancer cells use autophagy to survive. but equally having excellent autophagy is a bit cancer protective. So really, there's so much scientific complexity around some of those questions that is not always an easy kind of, yes, fine, let's go for the synesthetic approach and we'll do really well here. And with the colm to viscerotrol, it's interesting. So it's not symptoms. So I don't judge anything on symptoms because symptoms can be so varied and due to so many things. But what I find is high dose respiratory patients who had high dose respiratory and had a poor COMT function, I tend to see on the Dutch their methoxy is low. So their actual functional methylation activity of that COMT tends to be lower than I would expect. That's what I've seen. I've seen it mainly through that kind of methylation measure from the functional perspective. I see the methylation activity is generally lower. So if they've come to me on a big dose of resveratrol or quercetin, I would normally remove it, retest and see if the methylation will actually come back to normal a lot of the time that it will do so. So I have to be a bit careful with hyperdosing patients with slow comms on those. I wasn't sure if you were going to say, because of the shared pathways with dopamine, I wasn't sure if you were going to say something like sticky thinking and some of those other sort of symptomology. No, because there's so many different, and you know what, in cancer as well, because of sticky thinking, I mean, for goodness sake, chemotherapy will give you all sorts of interesting things. So is it your comp? or is it something else? Yeah, something else, yeah. I tend to not rely on symptoms for looking at enzyme activity. I'd want to have an actual biomarker that I'd looked at for that enzyme activity and I think it's a bit of a problem. A little bit like DEM, like... Like high dose DIM, I know you guys are not allowed to use it anyway, but high dose DIM with C1B1 is a problem. I've really seen a pattern of patients with that. Those who have really, really poor C1B1, it does drive for hydroxy. So over-dosing patients in DIMM is not always a good idea without knowing their genotype. And that's, again, coming from functional assessments, seeing a pattern of functions. And then you remove it, and then you retest it, and guess what? That activity has basically normalized or become much better significantly improved. So there's, I can, that's how I do it. It's an N of one trial and it's just by knowing that there's been some preclinical data within that setting and then I will look at the clinical biomarker to decide whether it has impact on that patient or not. But I always try and base it on objective data. Thank you. Cool. And then, yeah, some interesting things from Heather around the HPV and cervical cancer risk. with this DAPK hypermethylation. I've never seen a problem genuinely having supplemented a normal amount of 400 micrograms of methylated folate with any kind of hypermethylation. So it just doesn't happen in my clinical experience. But the other thing to say is I don't want a methylation of DAPK because I don't think we've seen it as a clinical test. in the UK. If you want to avoid it, so you need to think about the mechanisms for it. So do you know which enzyme is involved in hypermethylation of this? No. Yeah, so DNMT1 is the main primary. Right. And the accessory enzymes that can initiate methylation is DNMT3A and 3B. But DNMT1 actually has natural inhibitors. So EGCG is one of them. Yeah. As an example. And then curcumin, for example, is a DNMT3A and 3B inhibitor. So it can reduce the initial bit of methylation steps. So what happens in... that K is that usually DNMT3A and 3B start and then DNMT1 continues hypermethylating basically. So you can use combination strategies to try and reduce that hypermethylation. Yes, yeah and just then in terms of supporting methylation generally just normal doses being careful not overdoing anything and making sure all the supportive nutrients are there Exactly. And it's just, it's sensible things like let's not drive the wheel crazy, right? Yeah. If you think about, you know, that whole craziness of hyperdosing P12 in the folate is going at heartless speed. She's never going to have a good heart. And it's actually hard when you're looking at supplements to find ones that don't have masses of P12 in. It's crazy. It's like 20,000... you know, percent of just like... I end up using some of the Whole Food brands. So Whole Food from Time Health is quite reasonable as a B complex. And then as I said, Clare Labs, SFI Health, those two supplements that I've shown you guys are the ones that I tend to use the most because they just don't go, you know, above a reasonably sensible amount of B. And do you, is that always in like a B complex? do you always put all of the B's in? I tend to because I just think, you know, what you're going to do is if the methylation is a problem, I mean, it's very rare there's an isolated methylation problem and the rest of the B's are so fantastic. Like there's usually a mitochondrial problem and one of the other cofactors, which is the common one around mitochondrial function, B1 to B3 will be somewhere that's not okay. So I kind of tend to find that having done a number of OAT tests and other tests in my life that genuinely I've rarely, rarely seen methylation deficiency alone. You know, it usually comes with other co-factors. So I tend to give a sensible B complex because it'll work together. Yeah, brilliant. Thank you. Cool. And then, yeah, we'll do the tumor bits. I will definitely cover the case bits. I just want to cover all the rest of the bits and bobs. And then there was one around protein. So, yeah, so actually I've slightly revised some of my protein recommendations up a little bit more recently because the research is heading that way. So certainly within the postmenopausal setting, I now use 1.4 to 1.6 gram per kilogram as my average protein intake. and that's because of the more recent research so i haven't had chance to update it all yet but um on the course but that seems to be sensible what i can see the high is like over two grams per kilogram i don't tend to recommend i think that tends to be really high and actually we're thinking about really high to drive the igf-1 and mainly animal protein as well so there That's where the research seems to be. And certainly postmenopausal women need the 1.5 to 1.6. In older, like geriatric oncology, I might go higher. Like I might go 1.6 to 1.8 because they're very sarcopenic patients. And you will see that, Liz. You will see that on the test results because you will normally find, number one, you look at their general conditions, you go, you're a bit sarcopenic, you know, you've really lost muscle mass. You might, their sit-stand test might be a bit weak. You know, you can literally just get them to sit up and down in your clinic room and see how easy it is for them to use their proximal muscles. But also things like, unless they have problems with kidneys, look at their creatinine. If their creatinine is really low, you already know they're going to be in negative nitrogen balance. They're catabolizing their protein. They need more. And actually, they recently did a study where they looked at older people So, geriatric oncology and cancer outcomes, and they found high proteins intake were better for survival, unsurprisingly, but their higher was not very high, if that makes sense. So, this is kind of within a normal range. So, this is not giving somebody two, 2.5, three, you know, some of the bodybuilding ranges are very, very different. But we are looking at vast majority of postmenopausal women will need 1.4 to 1.6. geriatric oncology might need up to 1.8 sometimes people coming out of maybe tpn total parental nutrition they're quite often in really heavy negative nitrogen balance and they might need more so just make i guess make those adjustments according to what you think they will need and look at the bloods and look at the kind of muscle mass markers as well to make that adjustment i only i worry much more about you know thinking about your average person It's more about people who eat the standard British standard American diet, who are overeating the highly processed meats, the red meats, the saturated fat, animal fat sources. You really see them driving their IGF-1. Dairy is quite individual. And obviously what we see in literature is fermented dairy doesn't take to drive IGF-1, but non-fermented dairy, particularly things like milk itself, rather than maybe things like cheese. or yogurt for example, they don't have the same effects. What I tend to do with some of my patients who I know they already have other IGF-1 drivers so they might have a bit of insulin resistance issues so they will already be pushing that pathway anyway and if there is good evidence for that particular tumor type in IGF-1, I will quite often, and if they are resistant to reducing their DER, I will do before and afters. I will say, okay, fine, let's do IGF-1 now. And have I shown you one of my patients' IGF-1s? One of their... Oh, let me just show you. So this is one of my ovarian cancer patients. I'll just click on it for you. In her case, I mean, there was a major difference. Honestly, it was really, really significant. And she was quite resistant to reducing dairy. She is, I think, from Germany originally. So plenty of dairy within the normal diet. I'll see if I can find her test because that would be really interesting to look at. And in this case, it gave her the motivation to manage that better. Let's find it for you. I'm going to open that. I'm going to find it before and after. Probably with my patients, I have so many tests and I've been trying to hunt for them. Let's find this one. That's not it. It is really interesting to do it. So IGF-1 is run either by TDL or Randox does it. I'm not sure which other labs do it, but it may be worth having a look at. Yeah, here we go. Metabolic profile results. So where is that IGF-1? Two minute files. Here we are. So this was her IGF-1. And actually, she had a hyperinsulinemia as well, despite having a normal HbA1 disease. Look at these results. So that's an ovarian cancer survivor. HbA1 disease, 38. Look at that insulin. Look at that IGF-1. Right, 45. Right, that's significantly elevated. And she is very, very sensitive. So that's then... Let's open up other test results. Yes, I'm... It's a consent form, that's not an actual test. One second, I will find it. It dropped within normal range basically. So you will find... Oh yeah, here we go. Look at this one. I did find it. It did just take forever. That's a change. Okay. So, and that's fasting insulin. right obviously we were still working on normal anti-inflammatory side of things but one of the biggest changes she's made from the dietary perspective is remove dairy or cut down to a minimum fermented only how long did that take between those two results so that took about four months i want to say something like that one two three yes just so four months Yeah, so it will be individual, it will be different from that perspective. I'm not saying it's only one thing. So from the top of the fasting insulin perspective, she was like, okay, well, she's also after exercise, fine. That would have affected her fasting insulin, but the IGF-1 wouldn't have been affected by increasing exercise. So she was very explicitly dairy sensitive. So I'm not saying everybody's going to be that stark. Most of the time I see a drop. I just don't see a starker drop as that. But in her case, she was consuming a pretty good boatload of dairy. And when she stopped, you really did see that outcome. So yeah, it's just something to consider. As I said, not everybody listens. You might find there's no difference. You might find they're absolutely fine. But it's usually amounts and form that are the biggest problems with that. And as I said, fermented dairy is far less of a problem. It usually doesn't tend to raise IGF-1. And then we'll talk about the timeline in a minute. That's okay. And that's all. Yeah, we'll talk about this. Perfect. Okay, now it's all, I think Daisy only has one general question. We'll talk about protein. Protein, I think, hopefully we've covered that one. Daisy, has that covered your protein question? Yeah, would you say though, you know, the 1.5 to 1.6, would you say to them that's complete protein, like meat and quinoa, or would you advise them on complete, non-complete proteins, you know, assuming you're not avoiding any amino acids and things like that? I tend to look at total protein intake, to be honest with you. So when I assess it in patients, I will just get them to put their diet into chronometer for a couple of days. I'll get them to do it for three days, maybe over a course of seven to 10 days. I'll say, pick a few weekend days, pick a few weekdays. Let's just have a look at what your average protein intake is. And that's, I would just calculate that out from there based on their current weight. And I will just look at their normal protein intake. So that's the whole point. Actually, the whole complete and complete protein, as long as it's a 24-hour cycle, we've kind of shown that your normal protein, basically you can have an incomplete protein meal. And as long as you have enough complementary amino acid in another meal, that will cover you from that perspective. So that whole complete and complete protein from the plant-based perspective is is the research shows it's not quite true. You don't need to have combinations within the same meal necessarily. That plasma pool of amino acids is actually much more of a 24-hour pool. So I don't worry about complete and incomplete protein. So just look at total protein intake. And usually, a chronometer can give you some advanced information. If you think you're missing an amino acid, for example, or if you're worried about the overeating particular amino acid, you can look at the breakdown. based on the nutritional intake as well. So you can run advanced analysis, but when I just do a snapshot assessment, I normally go put your data into chronometer, let's have a look at how much gram per kilogram you're having. To be honest, the vast majority of time you'll just eyeball it anyway. I mean, you know, when you're looking at a breakfast, you know that there is absolutely zero chance that this patient eats 20 grams of protein in their breakfast. But sometimes we need to persuade them, we need to look at data. I will occasionally get them to do that and then say, okay, well, let's just put in those changes and let's repeat it again. Let's see how much you've improved. And people who like data are quite driven by that, being able to say, I need to have a look at that software actually, I've not used it. It's nice because there's a free version of it. There's also a professional version. So a professional version is the one that I use. So I basically send patients an invite. They have their own account, but I see their data. So they don't need to send you diaries. They don't need to ask to import, export data. They're basically all in your account. So you can just go in and have a quick look. We'll do an Omega-3, Omega-6 index, a few other bits and pieces as well. So I quite like it as a... good macro assessment and it's absolutely what I will use if I put somebody on a ketogenic diet. It has to be used because you're not going to ever get a reliable net carb count. It's going to take you forever to do it yourself. Get them to do it. So get your clients to do it themselves on a chronometer and then you'll look at net carbs because if you're trying to get some net carb 2025 with sufficient fat to count for enough calories within a ketogenic diet, you really need to have that data to the macro level to really and point something of a gram to be able to troubleshoot a ketogenic diet. So, chronometers play for multiple different reasons. Would you go as far as getting them to check whether they're in ketosis at home? Oh, yeah. Yeah, okay. So, I think some people say ketogenic diet, but they're not actually doing ketogenic diet. You're not in ketosis unless you've proven to me that you have a GKI of 3 to 6, right? Unless you have proven it to me, you are. Not in ketosis. It's just, there will be people, so many people, you're absolutely right, Daisy. I mean, the amount of times I get, I'm on a ketogenic diet and somebody's eating carrot soup and I'm like, yeah, like even if you've been ketogenic. Again, enough with gluten-free, yeah, right. Okay, I see. I was going to ask something though. Would you use exogenous ketones? Oh, Just a quick one. Would you use exogenous ketones? It depends on the context. Like somebody with messed up gut, there may be LPS translocation, there may not be digesting welfare and things like that. So it really depends. The problem is that I just wouldn't even touch a ketogenic diet in those patients. And the problem with exogenous ketones is nobody's done the research on how effective they are versus an actual ketogenic diet. Because a ketogenic diet is a complex intervention. It isn't just, oh, we're going to give you a bit of ketones. And the ketones within a... normal glycemic environment act differently to a proper ketogenic diet environment. You could remember that it's just adding in some ketones is not going to have the same metabolic context. So there's some interesting data potentially emerging that maybe either ketogenic diet or adding some exogenous ketones might help with CAR T potentially at some point. So that's very early data. We literally have just seen it and it needs to be corroborated. But that might be, I'd like to see a trial on that to say, why didn't you put people in one group, which is ketogenic diet, second group, which is normal anti-inflammatory diet with exogenous ketones and then the third group standard diet and let's see who does who does well is the equivalence because we just do not have that data so i don't use exogenous ketones unless the only time i do it probably is one very specific case if i have to send them into hyperbaric oxygen for whatever reason um and they struggle to get into ketosis before it and I need to just push them and I would normally get them to go in fasted on a fat-based snack and potentially give them some exogenous ketones to make sure they're definitely in ketosis before they go into HBOT. But this is like, yeah, I can count the amount of times I've done it on my hands. So it's very rare. And that's just because we just don't have good research on it at the moment. We hopefully will do because there's more interest in doing research like that. We just don't have that. And iron during active treatment, from my side of things, I think you've had that anemia lecture in module two, from what I remember, kind of outlines my iron approach from that perspective. It's not that iron is a no, it's just about saying, okay, let's just think about why somebody is iron deficient. But first of all, anemia-wise, right, what crucial information do you need to have apart from somebody's hemoglobin? Shout out to Marcus. first marker you look at when you get a full blood count and somebody has got an Hb of 109. You want the full iron panel, you want the transferrin, you want the ferritin. Before you even go over there, what's the next marker? The red blood cell volume, is it? Yes, mean cell volume, MCV. It's your first marker you go down. How are you triaging anemia? You have to go to MCV. It absolutely is a must. Because if your MCV is 106.8, do I need an iron panel right now? Possibly not, because it's highly elevated. Therefore, what's the most likely deficiency that's driving a macrocytic MCV 106.8 anemia? B12? Folate. B12 and folate. Two of those. Macrocytic anemia's high MCV is B12 and folate. Doesn't mean that's the only driver. There's many, many other reasons. Capucitabine will raise your MCV because it's a folate antagonist, unsurprisingly. But what I'm trying to say is your first bit is hemoglobin MCV. If your MCV is 72, do I need a B12 or a folate? Probably not, because the most likely anemia with your MCV of 72 or 75 or tiny, tiny red cells is... Yeah, 100%. But very seriously, you would be amazed the amount of people who, and I don't mean you guys, I mean the amount of GPs who prescribe iron for a macrocytic anemia, not having run an iron panel. And I'm like, this patient's ferritin is 500. Why are you giving them iron with a macrocytic anemia? Diagnose the anemia properly. Is it microcytic? What's the driver? Do your hematinics and then replace what needs to be replaced. But with iron, for example, I never give iron without lactoferrin in cancer, ever. Pretty much. It never happens. Because iron is pro-oxidant, pro-inflammatory, and because I need to support its absorption to the maximum degree and reduce the amount of iron-induced dysbiosis, I have to give something that will help them absorb the iron. So I will always give it with lactoferrin if I have to give it. but i don't always have to give it so sometimes when you think about iron deficiency anemia like the case i showed you in the module two her iron deficiency anemia was because she wasn't absorbing because she was inflamed after all of that dysbiosis because of the antibiotics giving her Less than five milligrams of iron as a probiotic, anti-inflammatory interventions corrected her iron status. I didn't need to go higher. I didn't need to go to 21, 28 milligrams plus of iron. So it's about having a stage intervention. It's about saying, if I definitely have an iron deficiency anemia, How do I replace it the safest way possible? Can I get away with maybe giving a tiny dose, maybe just giving lactoferrin with iron rich meals because it's actually not that bad, the iron deficiency. Can I get away with just giving maybe lactoferrin and an iron absorbing probiotic with a tiny dose of iron, like Biome Iron Plus. Or, you know what, this patient is horrifically anemic, their ferritin is five, you know what, I'm going to go in there because their anemia is going to be a danger to them having chemotherapy again. I am going to replace them with iron, with lactoferrin, I'm going to monitor them really carefully, make sure I'm not over replacing them. So we don't need to be scared of wine. It's just making sure that, point, curcumin has a reasonably short half-life. You know, you can space it really well. Just design a good spacing. I mean, a lot of these lovely teas that we recommend, they would chelate time as well. So, you know, having it away from foods and things like that is a simple... strategy because the tannins in the teas would kill a tannin. Yeah, but not all teas have tannins. So, yeah, so, Dianistema will have very low tannin content generally. So it depends on what tea. Yes, black tea, absolutely. If you talk about Camellia sinensis, it's definitely a tea contains tannins and we should be having it away from meals full stop anyway, because we'll have other problems as well. But I think it's about like, I have no problem with using curcumin. even patients have iron deficiency i just need to space it well from that perspective it just needs to be done cleverly understanding the half-life of curcumin and what about things like blackstrap molasses because it can be a bit sweet after meals if i have to add something in i'm like i'm just talking about there's so many iron rich foods that are normal like as in and if you go have to go veggies just making sure you're doing the normal thing of using them with vitamin c rich sources Lactoferrin is genuinely, honestly amazing. I've had one child, I remember actually we had, he was, his ferritin was, I don't know, five or six. And we course corrected with iron and low dose iron and lactoferrin in six weeks, his ferritin was over 20, you know, it was like 25, something like that. And again, you're given another four weeks and they're completely normal. giving 250 milligrams BD of lactoferrin, one dose with iron, another dose with an iron rich containing meal, usually every breakfast and dinner is the easiest, genuinely has a significantly measurable impact. And if you look at lactoferrin, lion loaded lactoferrin, versus iron sulfate, it's proven in randomized controlled trials that we have better outcomes, better ion repletion with an ion loaded lactoferrin. There's pregnancy trials, there's children's trials, not so many cancer trials, but you know what? Having used it, it's literally one of my favorite things to use. And because of this anti-inflammatory action, you're just buffering what you're giving in a clever way. And even barring somebody who has a dairy allergy, not an intolerance, but an allergy, it's really, really safe to use in a good majority of patients. So how frequently do you monitor iron after they've been replenished and there's normal supply? Good question. I guess it depends for me on, you're my favourite, I'm saying it depends. So it depends on the drivers. So it depends on the drivers, what is driven the iron deficiency in the first place. So say, for example, I don't know, let's talk outside of cancer. Let's talk, you know, typical heavy menstrual bleeding, right? You know, I've course corrected the heavy menstrual bleeding. I will probably check it for the first three to six months. And as long as the bleeding is controlled, the iron should be controlled. I don't need to constantly recheck it. Same with cancer, if that cause was because they were horribly depleted during anaemia, during chemotherapy, and the chemotherapy is finished, and they've optimized their ionoderm to continue rechecking it. But there are times when it's unaddressed or they're continuing chemotherapy or the other things, in which case I would check it regularly because the drive has not been unplugged because I can't unplug it because they've got metastatic cancer and they're continuing chemo. Do you check it, what, every six weeks, every four weeks? No, four weeks I tend to find is a bit much. Depending on the degree of deficiency, I would say if I'm actively correcting it, probably every six to eight weeks. And then once it's plateaued, usually every three months is sensible. If they have a good reserve, they normally can last three months anyway. And you will see their decline, so you can kind of pick them up before they drop anyway. Cool. Right, let's now do the exciting things about the case. So, I'm going to go through things. Can I just ask a very quick one? Sorry, do you have a favourite laxapherin brand? Because the quality can vary quite a lot. It does vary. I'll tell you the one I use most. But equally, honestly, from my side of things, as long as it's... So, I use the Jero one the most. mainly because it's accessible and it's usable on a meter and usually it doesn't tend to guard itself too much. the other thing today that's once in the morning once in the for dinner time yeah you can give a lower dose like biofilm from biomedical has 100 milligrams of lactoferrin as well as well as a bit of iron so that's also an option from point of view of budget it's a more budget friendly option but lactoferrin only has a really significant effect and i would say a good dose so i don't i expect that you know biking works very well But if I'm trying to use lactoferrin for its kind of anti-inflammatory effects as well as iron supporting effects, I tend to go for a higher dose. So I might give a baby biohium in the morning if there's a budgetary restriction for how much lactoferrin I can give and give it 250 at dinner with an Irish meal because I still need more dose usually than that. And it doesn't have to be taken every other day with some iron supplements does that? Lactoferrin is fine because it's not reliant on hypsidine so it's no hypsidine down regulation so obviously with normal iron yes you can alternate it from that perspective and it's because mainly of the upside inside. Lactoferrin you can continue taking every day and that's what I tend to do. I mean to be honest my poor cancer patients have to cook with so much already and what to take and not to take and etc, etc. If you can make life simpler, let's just make it simpler, right? Yeah, if you gave iron by itself, yes, you'll have to follow the whole maternidazine rules, but I don't find that with lactoferrin, it has any bearing at all. I find it normally has really good results either way. Right, let me find my little, where did it go? Okay, cool. So Susanna's asked a question about the Cyrix food allergy results of 46 antibodies that she's avoiding. Guess why I have not given you this information. Right, so first things first, does Cyrix test for food allergies? It's not food allergies, is it? Isn't it IgA and IgK? Is this a food allergy? IgG is, isn't it? No? IgE is the only known allergy. Sorry, yeah, I was thinking of intolerances, of course. Exactly. So... Is she allergic to any foods? Because I haven't put it down on any of your paper ones. She's intolerant, but that could be due to leaky gut, right? 46, I mean, come on. All you need to know is 46. I just give you a number. Is anybody in this group going to restrict a patient with cancer from having 46 foods? No. Yeah. but but this there's a reason why i did not give you a list effectively so you have to what i would assume is number one she has no allergies because i specifically gave you all of the allergies she's had okay so this inside does not test for food allergies just ig and ig exactly like melody says food intolerances okay food reactivities whatever you want to call it not allergies You can make any assumptions you like around those 46. I would just tell them they're moderate in nature. None of them are in red. None of them are severe. They're all in amber range from that perspective. So you just have to make a plan. You can make any assumption. You can say, okay, you know what? I'm assuming that all 46, she doesn't actually have any symptoms. I can tell you that now. When she eats the food of the 46... She doesn't have any symptoms. She's been excluding them on the basis of a test with no clinical symptomatology. That's what I want you to know. Okay. And then you can make any assumptions, any assumptions you make, don't worry. All of you will have different plans. I expect that. That's normal. In fact, if you have same plans, I will have to check the plagiarism. But genuinely, just make any assumptions. If you say to me, I am a C-Rumain, X, Y, and Zed, then I will know what you're assuming. Like somebody asked a question about alcohol intake, said there's no alcohol intake mentioned in the form. There isn't, she doesn't drink alcohol. But you can say, I am assuming that there is no alcohol intake. Then I know that you thought about it and there is no alcohol intake. and BMI again the overweight underweights and I think that was spotted by one of you is that she's got normal BMI is that she thinks she's got more weight around the middle that she would like and therefore that bit is overweight and the rest of it her arms are quite skinny so she's a bit underweight her BMI is normal if I didn't tell you that somebody is obese or whatever else or they're horribly underweight assume it's normal but you can always write it down as an assumption that you're making because Because without a clinical history, I'm aware of the fact that you are limited in what you don't have a conversation with somebody for an hour, an hour and a half. So of course you're going to be limited in clinical detail. So just put down any assumptions that you're making and it's absolutely fine. If I know what you're thinking, it's great. If I don't know what you think, that's usually when you can lose marks. Just tell me what you're thinking and that'll be fine. Heather wanted to ask one on her, she had her MGS testing the tumour, reported there was no BRCA1, BRCA2, no mention of B53. Is it because of hallmark or was it in focus of the clinical decision? So this is going to be an interesting one. So I'm not assuming you know anything about high-grade serous ovarian cancer, but there is absolutely a clinical relevance of BRCA1, BRCA2 in this setting. So you will, when you research it, you'll learn about it. If you're BRCA1, BRCA2 mutant, you have an option of having something called a PARP inhibitor. So that is, and that's much more highly effective in those patients than it isn't, than it's in others. It's not the same for TP53 or any other genes. When they do germline testing, they don't usually test just one or two genes anymore. They used to. They now will run a pretty comprehensive panel that includes other things like CHECK2, PALB2, TP53, other things. But the reason they specifically mentioned that one is that BRCA1, BRCA2 have a particularly high response to number one platinum agents, platinum chemotherapy, and number two PARP inhibitors. So yes, they're reported clinically relevant stuff. P53 has an interesting thing. So there's two ways in which you can have abnormal P53. Anybody want to gather, hazard a guess on which two ways? You had a bone there or is it DNA damage? So the first one is somatic and then there's acquired. So there's a germline mutation and that usually causes Li-Fraumeni syndrome. That's a genetic syndrome where somebody gets an increased risk of all sorts of cancers. So that's called leaf ruminants. That's a germline mutation. You're born with it and you're going to have a really high, most patients will get cancer by the time they're 30 of some sort. Okay. They're really heavily monitored through MRIs, et cetera, et cetera. But not CT. And why not CT? it's much more dangerous than people with p53 mutations because you can't protect yourself from radiation damage okay so part of the problem we don't monitor those patients with high dose cts we only do it when we really really have to but um the other part is most cancers exactly like you said have a p53 mutant within the tumor itself okay and that is very very common and unless you have a targeted therapy or some kind of relevance to it they'll report it but they won't really do anything about it per se, it's just one of the really commonly mutated genes. We focus in medicine on mutated genes that we have targeted therapies against. So that's a bit like P53. There is not a licensed P53 therapy I can give a patient right now. And therefore, it's not that relevant if the tumor has got mutated P53, apart from the fact it might affect how aggressive that tumor is. So there might be other things that we might be thinking about. But a lot of the time, what you will see reports in oncology data is the stuff that's relevant for the drugs. So for example, they are MSI high, microsatellite instability high. That means they're eligible for immunotherapy, no matter what cancer they have. DMMR, they are deficient in mismatch repair, which is one of the gene protection pathways. Again, that means they're eligible for temporal isomers, so immunotherapy with immune checkpoint inhibitors. So you will see some of those bits and pieces, and then some of those genes will affect aggressiveness, so they will tell you which ones maybe are this mutation, aggressive phenotype. So sometimes it will have things like that there. But yeah, basically don't worry about the p53 in this particular case. So MRI in September 2020, no measure of a CT scan. Why would the MRI be chosen over a CT scan? So that's a good question. Let's do it. So why would you choose an MRI over a CT scan? Specific and more detailed for the area. So, pelvis in particular, you've got to remember MRIs are actually much better differentiating structures that are close together of similar density. So, MRIs of the pelvis are usually much more accurate than a CT of chest, abdomen and pelvis. They're better from that perspective. But the other thing is, guess what this patient's trying to avoid? Radiation. Radiation. Yeah, so she would rather have an MRI because it visualizes what she needs to visualize in the pelvis without giving her extra radiation. So there's two reasons for why we might choose to do an MRI. There are certain structures that are just better visualized by MRI as well. There is a reason for why you have a spine MRI and a brain MRI if you really want to look at the brain. The CT is pretty rubbish unless you have a big hulking something. CT is like an emergency medicine way of viewing the brain. MRI will actually give you a proper picture. It very much depends on the structure, but in this particular case, because I know the patient, I can tell you this for two reasons. One is it actually was a good way of imaging the pelvis. which is where they're looking for the recurrence and two is that she wanted to avoid radiation. So is it normally discussed with the patient, the difference between the MRI and CT and they're given a choice or is it sort of like this is what you need? they're just getting told what they need. - This is what you need. - Or you advocate for yourself and you turn up and you go, I want this scan and your coach just thinks you're sensible then they'll give you that scan if it's within their parameters. And they're good friends with the radiologist who's not gonna kill them for ordering something that's off the cuff. So yeah, usually there's protocols and the protocols are there for a reason. But for example, what's our standard way of monitoring for breast cancer accounts? If you haven't had a mastectomy. Ultrasound? No, mammograms. Mammogram. Mammograms, yeah, okay. Now, which, and again, you might not know the answer to that, it's absolutely fine, but if you work with breast cancer, you've encountered breast cancer, which breast cancer shows up quite poorly on mammograms and has to actually have MRI surveillance most of the time? The deep one, if you've got deep tissue. Mammogramic density plays a role, but that's not it. It's lobular. So lobular breast cancer is usually quite poorly visualized in a mammogram, so you can in fact miss it completely. And usual surveillance is via MRI. And I've had to fight to get my patients MRIs, but I'm like, you will be monitored via MRI because that's the international guidelines. Just NHS doesn't always follow international guidelines. because MRI is more expensive. But for lobular breast cancer, if you have high risk of recurrence, there should be an MRI there somewhere because the mammogram is unlikely to detect that cancer as well as others. How is that type of breast cancer detected then if it's missed? Yeah, so usually what will happen is the mammogram might not see it the first time around. They will get big enough to then eventually either be seen or palpated or they just palpate and they go, there's definitely something here. It's abnormal. They might see an ultrasound, sometimes better than the MRI actually, or there's just a lump and they go, "I'm going to do a barista MRI because it's a suspicious lump and I can't see anything in the mammogram," they will account for that. And I mean, mammographic density obviously plays a role, but I just think lobular is one of those cancers that is quite underestimated in terms of it does require different surveillance than a normal ductal type of cancer. So you don't see NHS patients, you see private patients, is that right? I mean, I see all patients, but just unfortunately my clinic is private because I don't work on the NHS. So I will see patients who are managed by the NHS and therefore normally I will write a letter saying, as per the international guidelines, You know, and usually, usually you just need to push them. It's one of those things that they kind of are aware of it, but unless somebody pushes for it, they will do the cost-effective thing for the NHS effectively rather than the right thing for the patient, which you've got to remember, we are in a socialised society. service, which is wonderful, but the socialized service is designed to deliver the most benefit to many, not the most benefit to the person. So there's a very, once we understand that, we kind of understand how to make the decisions from that perspective. But I'm there for my patients. So frankly, if they want to spend money, if they have to spend money on MRI, they will have to spend money on MRI. Are there any benefits to the CT scan over the MRI for any cancer? Good question. So PET CT, yes. Not necessarily CT, CT. I'm not sure if there's anything with CT. So just cost. But PET CT, well, cost and time. Because how long will it take you to get a CT of the whole body? Like four minutes, probably five. How long does it take you to do a full body MRI? Over an hour guys, okay? So think about it in terms of NHS waiting lists and everything else. Would anyone rather do a five-minute scan? That's much cheaper and again the cost-wise is probably between maybe half to maybe third of the cost. A CT vs MRI depending on the extent of it, sometimes even less. So it's cheaper, it's faster, and it will give you reasonable information for the majority of the time, unless you are in the biggest special groups that don't get damaged well by CT. PET-CT does have advantage over MRI sometimes, because I do have to get PET-CT sometimes. We don't like the radiation, nobody does, but if I don't have good information on the patient's cancer, what's more dangerous to them? The one of dose radiation, not knowing what's going on with their cancer. Not knowing what's going on. So why PET-CT versus MRI? What does PET do? What's the big advantage of PET? It shows the cancerous region. The real take of radioactive sugar, so you see what... whatever formations are metabolically active, right? Yeah, exactly. And it's just everywhere, the whole body. Because I'm not going to MRI the whole body. Nobody in the NHS will do a whole body MRI for you, okay? So usually, when we're surveilling you for cancer, we will go, you can have an MRI of abdomen and pelvis because your cancer is gynecological. But actually, if you've got lung mets and I haven't scanned that area, guess what I'm going to miss? The lung mets that light up like a Christmas tree and a pet sick tea. Or maybe you have a met in your humerus, in your arm, in your bone of your arm. I've never, ever seen it in MRI because I'm not going to MRI your arm because you have no symptoms in your arm right now. So there is, there are, and there's other bonus accounts as well. But what I'm trying to say is that imaging modalities usually will very much depend on what you're looking for. And it's never a simple question of saying that everybody should have one thing or everybody should have another thing. It's, it should be based on the clinical situation, what you're looking for. What are the realities of requesting galalidium free? Because I know that can affect a lot. You get a poorer picture. Yeah, but the problem with no contrast, you get a poorer picture. So you have to, again, it's a discussion with the medics to say, like, actually, without contrast, will I be able to see enough to make a good medical decision on your treatment? So that's the purpose of it, is that actually without contrast you're not going to get a good picture. So sometimes we have to do CTs without contrast because somebody's got chronic kidney disease and they're not going to handle contrast. But we are aware we're going to get a crappy picture. So therefore we're going to have to factor it into our clinical decision making. So there isn't, trust me, I would like to avoid as much as humanly possible, if you have a high test MRI, you know, if you have... really good MRI scanner, you don't usually need contrast. Okay, because the scan is so powerful, I don't need gadolinium to make the picture better, particularly with the new AI side of things as well. But how many good new MRI high Tesla machines do we have on the NHS? Not that many. They're mainly centered around the big centers of excellence like the Christie in Manchester, you know, World Marsden, some of the places. Your district general MRI it's highly unlikely to give you a good picture without contrast. Unfortunately, it's not powerful enough. Yeah, that's why it's good to know there are some at least. Yeah, I mean, not to mean nothing has the new research one that I would love for my center at some point. I think it's like 11. Let me just find out just for my own. I think there's 11.2 or something. It was something ridiculous. I'm close to Addenbrooke's, which is obviously a huge hospital. Do you know if there's any there? yeah yeah they should do they should have a good high test mri but yeah 11.7 look at you i was down by 0.5 but hey i remember it was 11. um so 11.7 tesla now you will not need the gadolinium contrast to get a good picture out of that scanner it is one powerful powerful magnet but um and that's what the new uh things like maneuver etc some of the newer scanners that are have been installed in the us are coming over to the uk the kind of whole body MRI type of screening things that we talked about last time. That's what they rely on is the fact they don't have to do contrast and they don't have to have any contrast facilities because they have good powerful scanners, but an AI capability for image analysis effects of no soap. But yes, anyway, that's an interesting one. What else we can do? Oh yes, patient timelines, let's see. Yes, I'm trying to. It's really tricky because I'm trying to have to redact some of your bets to make sure I remove enough identifying information. So it's a bit tricky on the timeline. So when baseline is, all of your questionnaires are current immediately prior to your NT consult. Basically, you've seen this patient. Baseline is baseline. So baseline. assume um maybe get alcohol consumption wise if there is if there is missing answer you don't see any alcohol on a food diary you can assume they do not drink right that sort of thing that's fine in terms of overall timelines for the supplements i think you should assume okay from my perspective they've been they're seeing you i'm going to give you a timeline because it's rough timeline they're seeing you Late spring, kind of early summer 2024 for the sake of this exercise. They've done this test, remember the GI test? They've done it in August 2023. You can assume their current regime started then because all of their gut supplements were started then. So you know that's where they started. They had a blip with a DCA earlier this in 2024, the magical year in which we're seeing them, which they stopped because they had horrible neuropathy. Okay. So you can assume that's no longer on their list. So they're not taking that from that perspective. Now, somebody noted there were some zeros in one of the protocols it says zero per day and that's because they're cycling them so they're taking them some of the time they're taking them some of the other of the time so you can assume you're going to rework the whole supplement list which is why i didn't focus on the detail you will need to figure out what you're going to do with the supplement list they're taking all of the supplements on the list at some point over a course of a three month period is all i have to tell you Whether you want to keep this lovely three months rotation going or not is completely up to you. But this is just something you need to be aware of. So in terms of interaction checks, you interaction check all of it because they're going to be taken at some point on the medications that they're on at the moment. And in terms of the timeline, if we're seeing them spring, early summer 2024, when are they starting the immunotherapy? I think I said in the thing it's within four weeks. I believe I said it's in the briefing period. So you've got four weeks. Please. Four weeks. Yeah. What I would avoid is just try and be sensible. You've got four weeks roughly. Until immunotherapy. And then they're going to continue on this immunotherapy for the foreseeable future. So just assume they are on immunotherapy. That's what I would do. Artisim is interesting. It's basically this. There we are. It's basically artemisia annua. Wormwood. People love wormwood. There we go. That's what it is. Yeah, I had a question about that. It was saying artisan protocol, and when I looked it up, it was saying Chinese woodworm, and that came up, and I was just wondering what else was related to it. So that's just part of what you're giving them now? Well, we're not giving them anything. They've come to you from another practitioner who decided to give them a lovely three-month protocol of various stuff, which may or may not make sense. Maybe it makes more sense to you than it does to me, but hey. But yeah, you can assume this is Artemisia annua, so it's wormwood, which is a pretty potent antimicrobial. I'm really sorry, but so on the notes section it's saying it's part of the artisan protocol, but then artisan is not listed in the actual medication list. I know, I think what they've done was, I think Again, because I know the special detail. Basically, the gut supplements that she's on after that is like what she takes after the artisan effectively. So that's why it's not on her list at the moment. It's a bit confusing. I'm sorry. It's what she's provided to me. So I had to do a lot of digging to try and investigate what is missing taken. You can assume that she is just taking right now what she's on before, but you can also assume she's taken artisan in the past. So think about what effects that might have in the overall picture of the plan. So this current supplement protocol we've been provided, I mean, it looks huge. Is that... I didn't realise, so that wasn't from you, but my first thought was, my God, how could anybody ever comply with that? So this isn't a normal sort of size. It's ultimately organised. A lady in the whole wide universe is all I have to tell you, and she is compliant, but you make a very good point. And unfortunately, what you will encounter is, you will encounter when you work with an individual in a space that is slightly... crazy spectrum of people come to you and they don't know food matters and they maybe are resistant to having two supplements and then you'll come the people will come to you on plans like this okay or the Jane McClellan bonanza of all sorts of interesting things and then you're supposed to sort it out and honestly you will be in both situations it's just it's one of those things but yes it's it will be far from the only time you will ever encounter things like this is all I have to tell you I want to prepare here because it's a good time for you to go oh my goodness Yeah, and that was my reaction. Ask me all the questions, ask me all the questions, work through the case, so that when you encounter in clinic, and you might be by your lonesome at that point, you go, oh, okay, I know how to start with this, I know where I'm heading here, and I know what's sensible, what's not sensible. So I did it deliberately because you guys are, you know, a lot of you are experienced practitioners here as well, so, you know, you will not be kind of going, okay, I can only recommend, you know, two changes in one supplement or whatever it is, we're not in training clinic anymore. But equally think like you said of the manageability of all of this. She is compliant because she is supremely organized. She used to be a microbiologist in labs so she is supremely organized, she's amazing. But is it clinically effective? Do you know? Well also to me that to take that many is like how on earth is her body actually dealing with that many supplements in one go? Yeah, yeah, yeah. Yeah, alone the cost. You can pass and discover and tell me all about. So there you go. Okay, I was just, I just thought, oh my gosh, maybe that's sort of the thing we should be aiming for. I thought that was from you. Trust me, you will not see. If any of you guys see a patient from my clinic, you will not see this. Now don't get me wrong, it doesn't mean that my patients sometimes don't have a lot of supplements. Sometimes they are, okay? Particularly when it's a really tricky situation trying to dig themselves out of big holes. They're never on that level of stuff. Not in a three-month rotation plan with random antimicrobials and prebiotics and probiotics at the same time. It's just... Yeah, there's some logic that has to be applied to these things. Right, MD Anderson. The next question was about MD Anderson, MDASI scale and the worst, the best of the worst bit. So just so you know, if you ever encounter scale you don't know, we Google it anyway. We'll have a look at it together. So MDASI is here. Okay, you can have a look at this bit. And then we can usually, you can have a look at an example from the index perspective. So let's have a little think if we can find a nice one. Oh look at that! It tells you exactly how bad you can go. There we are. So you go from 0 to 10. But you guys should be able to hopefully just google it and be able to find out what the scales are like this. So that's in Darcy for you. What else have we got? Yeah, off-label drugs for the COC. So what are the standard off-label drugs for the COC? Shall we Google it? So just Google it. You'll know the four off-label drugs for the COC. It's really easy to find. It's not difficult. So assume she wants to take the four drugs. and whatever supplements they will recommend and you can decide whether you want to go down that route or what you want to say to that person. First part of the assignment, so the idea of the first part of the assignment, it's not stupid at all by the way because it's an important question to ask how you're pitching it. Imagine you're writing, you're referring your patient to me, okay, and I want to know everything about them in half a page of A4 because I don't have time to read three pages. I want to have a professional summary. So you want to try and tell me everything relevant about the patient as much as humanly possible within half a page of A4. And that's the one that's restricted for a really good reason. If you're going to write two sets of page of A4, you will be penalized because it's restricted to test your ability to summarize complex data within an easy doctor's letter or letter to a professional whatever it is you want to write so that's how you're pitching it it's a professional summary half paid so we're just we really are just taking out because all i'm thinking is really you've given us a brief overview of the case and i didn't know whether you wanted us to go into more detail about the type of cancer or if you were just wanting to know our thoughts on what's happening to all of her systems that's what i was So if I received just your summary, do I think I'll know enough about a patient to make an integrative care plan? No. Exactly. So that's what you need to do. Okay, that's fine. I just wanted to check that. Thank you very much. Yeah, but otherwise you're right. I did give you, like, if you were writing to a medic, what I've given you is plenty to put at the top of the letter for them to know everything they want to know about the patient. But I am a weird medic. I want to know a lot more about the patient. Okay. Okay. Tell me everything I might want to know. But again, what I'm trying to say is, yeah, I might not want to negotiate for dinner last night, but equally, anything that you think is relevant to a professional sample of the case within an integrative oncology plan is out. Lovely, thank you. And then, sorry, I'll just quickly answer Sarah's question. She asked about a TDL blood panel that was a baseline and then a the client says her hb was 99 and was already included yeah her hb is still 99 so guess what she's still anemic so your everything that you have received this paperwork is current so assume the test results are current they're right now in four weeks she started immunotherapy assume the all the answers are currently assumed that supplement plan on a three months rotation, you have no idea which month is current, but basically you have to check everything. So, which because sometimes that would be the situation, they might not even remember what they're taking. So assume everything is current effectively. You're about to see them and write a plan or you've seen them and you're going to write a plan. And then final bit, rough word count for each section. I deliberately didn't give you one. I don't give you flexibility mainly because I can't restrict you. I don't expect gigantic essays. This is like, this is an in-tech level. It's a level seven assignment, but I'm not expecting a master's. This isn't $10,000. world masters ridiculousness just give me a sensible sensible clinical plan all i want like from my perspective just think about what i would want out to you i want to know are you clinically safe and effective out there working with a patient with cancer that's what band asks me to certify when i give you a certificate that's what mtex asks me to certify that based on your assessment not on your clinical practice but based on that assessment you give me I am confident that you should be reasonably safe and effective in your clinical practice as I have assessed by this piece of writing. So as long as you give me this, I'm good from my perspective. If any of either the safe or the effective is gone, you can imagine that's going to be a problem because ultimately we are one of the approved courses for the directory for a reason. And I always say to people, because I think sometimes within particularly the NT world, there's assumptions you're going to pass. Please don't assume you're going to pass. You need to work for it. I promise you. And that's because this is a really vulnerable group of patients. And when I say you've passed, many people have retaken an assignment. I promise you. Because they've assumed there's going to be an easy piece of work. They've tried to bash it out in about two to three weeks. And they found the standard wasn't high enough. And it's not me being mean. I promise. but it's because I need to be able to put my name online to say you're good enough to enter that directory. And obviously it's not me certifying your clinical practice, it's just based on what you are writing for me. That's all I can see and assess you on. So don't write 10,000 words, but equally, you know, don't try and give me two references because guess what's going to happen? It's not going to fly either. Are we writing in the first or third person? You're writing in academic language. So which person are you writing to? Well, that's the distance. Think of it, it's an academic assignment. Pitch it at level seven, if you can. So it should be a post-grad piece of assignment. It does not need to be flowery. I don't need to know ridiculous language. I'm very, very simple in the way I mark these things. But the key thing is safe and effective. There are two key parameters to hit. And you have the mark scheme, so you'll know, like, once you've done your assignment, just sit down, work through the mark scheme and say, out of each line, have I attempted to hit each line? Because that's why I write the mark scheme, so you guys can check it afterwards and say, oh, you know, actually, have I bothered checking my reference? Is it the right style? The amount of people who try to submit it with the wrong referencing style is actually astounding. I think everybody's learned that now. But just simple things like that, because that's a fail automatically if you don't reference correctly. I need to rehash Mendeley. I wonder whether it's still out there. That was quite easy for referencing that app when I did my masters. I don't know. But anyway, I think there's lots of referencing software. I think the key thing is just use the correct style and do check it that it makes sense from that perspective. And don't try and sneak references, don't say what you're trying to support past me because I know the literature of the odds reasonably well. So if you're going to tell me, make a big claim and then back it up with preclinical data in a tiny cell in an irrelevant chamber, guess what's going to happen? It's not going to fly. So yeah, just be sensible. Honestly, I am a harsh marker because of the fact that I've always been in a system that's marked harshly. I was a tutor for a Cambridge college. My background is not British, so I will mark harshly, so I don't expect distinction, mainly because it's really, really hard to get. But I will also be fair. If you made a point, you will make a point, and it's fine. If it's referenced, if it's well backed up, and even if I don't agree with it, I will give you that point because you made your argument. I don't need to agree with your clinical practice to think you're going to be an excellent practitioner because there's no point to... you turn out close to me, you all have beautiful experiences, you won't pass on taking something. So it's just about being really clear, backing up what you're saying and being good at referencing and making sure that you're addressing the case properly. Because it's a clinical case. I want to know if I send you my patient, which I refer a lot out of the clinic, actually, particularly if somebody's local and they want to see somebody else in person. And so I'd love to be able to refer them to you, but I need to know that you guys are going to do a sensible thing, which I know you will absolutely try. So just show me, just demonstrate it to me so I can take the advice. That makes sense. It does. And how long, because I have dollar masters like Daisy, how long do you think realistically it takes? Because I know we've got two months now from the beginning of May, or from today more or less. Yeah, right. I would say don't leave it any less than four weeks, mainly because you'll need to go back to it and have a look at it a couple of times. I would say just because this case is not a, oh, well, let's just do an easy case. You will need to do a fair work for it. So I think it's a reasonably involved case because you've got a few things to think about. So I would say don't leave it less than four weeks because I think you just need that bit of headspace to sometimes mull things over because it's a new area. It's not a new area for you in terms of nutritional therapy, but it's a new therapeutic area. So if you don't know what the typical side effects are of drugs or what are you expecting of this kind of cancer and the previous toxicity, you might need to go away and look this up. And that's what takes time, really, from that side. Does that make sense? Yeah, yeah. Good stuff. Any more for anyone on their side? Can I just ask, on the questionnaire, she says there's a family history of cancer, but we don't get... told what that is or who it is? Is that deliberate? Yeah, it's not. What I would say is from your perspective, it is prostate cancer in a 75-year-old gentleman. And so it's not relevant to your particular case. And it's a single case. So it's not a heavily family history of cancer. Okay. And then the fillings, there's a date there. So it's indicating that she's got them, but we don't know how many. The date is when she's had them removed. Oh, which is the removed, okay, sorry, missed that. Yeah, yeah, so you can assume she does not have, actually her dental work has been complete, so that's fine. All right, great, thank you. I was going to ask you about the Jane McClelland book response, which I read the book years ago, I'm rereading it again. It's actually really interesting. Do we have to just go... And list all the drugs that she talks about, obviously off-label drugs that are being used and the reasons why, or do we just say it's outside of our remit, they're not studied in cancer patients, certainly not studied in this type of cancer. Can do it. Tell me, Daisy. I'm not giving you the answers. Okay. I'm just fascinated. Actually, I googled her the other day. She's alive and kicking and she's doing cancer courses, which obviously she's not qualified for, but I know. I have to give her the credit. Yeah, yeah, yeah. I'm not touching that one with a barge pole, is all I have to say. I just think everybody should stay in their lane and I think everybody should be really clear on the evidence base that they do courses or any other training on, is all I have to say. And I think you have to be really, really careful. I think there's lots of people spouting all sorts of little soundbites for various bits. And the amount of unfortunate patients I've had who go off and get various protocols of the internet and then come to me with a complete calf crash is huge. And that's the problem. The problem is, and there was another person like in one of our NT clinics, he's read, he's a guy with a high risk of recurrence for prostate cancer, okay? Keto is apparently a fantastic thing to do for cancer. So he's put himself on carnivore keto. Boom. Uh-huh, you go or wins. How would he know if it's not good for you? Cucurbit is fantastic for cancer people, come on. So, and boatload of supplements. And you know what? He came to us hypercalcemic, right? With a worry about recurrence of his cancer. So we've normalized his calcium now. We've stopped a lot of supplements, we've changed the diet. And actually he's now no longer hypercalcemic. We're just watching him carefully. But this is not trivial. You really can do significant harm with Cucurbit. people spouting crap about things on the internet without doing any caveats. You know, even people like, you know, there are certain, you know, there's a researcher and herbalist who decided one supplement all cancer patients should take. So any of you know one of those? I don't. because actually there's even a contraindication for vitamin D. So what I'm trying to say is that the one supplement was MCPE, which has precisely two studies in biochemical recurrent prostate cancer. And apparently this is the one supplement all the cancer patients should take. And I'm like, And then you even read the comments and one of his clients comments and he goes, oh yeah, he's put me on this dose. So I'm like, you've put on a third of the doses in the randomized control trial. She does not have bicalcular prostate cancer. And you're telling me it's for everybody? So that sort of stuff pisses me off and you will see me be an Instagram gremlin sometimes because I will start telling people this is not okay because we're working with really vulnerable people and really vulnerable times in their lives and it's just not okay because people grasp at anything, you know, and this is, yeah, so anyway, that sort of stuff just pisses me off. But are there places, you know, some of the more proven like the statins and things like that, are there places where doctors would use them? Would you... I will use a statin if I have a high-cholesterolemic patient with high-risk seroseverine cancer, and I will choose a lipophilic statin, okay? And I will make sure I don't run their LDL too low. But you can look at the trials, which I will use to back myself up on from that perspective. So there is different ways of managing all of this sort of stuff. So it's not that there isn't a place, but this over-claim of single supplement is boatload of overflaggable drugs of no research on patients who might already be on a polypharma so six other medical patients with lfts that are high nobody told them a statin is going to kick their liver Guess what? Nobody's giving them the contraindications. When have you seen a well-balanced argued discussion of this? Oh, here's the pros, here are the cons, here might be some of the side effects. Please check with your practitioner. Make sure you've done a drug interaction check. How many of those do you see on textbook? You know, it just doesn't happen. So I think that we have to be a little bit careful and it's just, as the medic, I have to navigate all of the playable stuff all the time because I'm actually the prescriber. You know, for you guys, in a way, it's easier. So it's, we just, our side, we do have to discuss pros and cons of data, what it does and doesn't say, what are the biomarkers, what are contraindications, what are comorbidities for patients, why they cannot take that starting with their LFTs in the 200s and 300s, you know. There's many, many things. It's very much a contextual question and it's what patient, what stage, what are the medications, what biomarkers, even like what statin, right? Not only hydrophilic, lipophilic, but also have you done the pharmacogenetics? Are you going to know they're going to detoxify properly? We run pharmacogenetics in pretty much all patients about protein and statin. to make sure that I minimise the risk of any problems. And so far, I haven't had anybody who's had a significant issue with the statin, but that because of pharmacogenetics. So it's that level of thinking, which just doesn't come through most of the time, whenever you either read something or listen to something. And that's why you kind of need, it's a clinician level decision. It's a little bit like, you know, somebody spouting off about a single supplement or coming to see one of you guys. Right today, right? Completely different. Here's the probiotic that everybody should take. I'm sure you'd love that one. You know, everybody should take this particular. Oh, no, everybody should take 50 billion of subrandom bacteria and they will improve all problems with everybody. You know, it's this sort of thing. It's ridiculous. But we are making it like the amount of tolerance for this within the cancer community is ridiculous. We need to start weeding that stuff out so patients get good high quality information. Anyway, I get off my high horse now. Anything else you want to ask me? Just one thing, because I've been dealing with, at a very gentle level, with cancer patients through a charity for a really long time. We've got a doctor here in Majorca that's very prone to giving all these breast cancer, well, mostly breast cancer cases. They're all on expensive infusions of vitamin C and also glutathione. And I'm like you, I can't... it's now i've gone through this course with you and it's just constantly coming up about the antioxidants it's like when they come to me now and i know they're paying a lot of money for it i just have to say well i'll work on your food but i'm just not on the same page as him because i can't personally start spouting off about what i think you know i'm working as a volunteer for a charity and I wouldn't do that and obviously you've got to always look after your own business but I just say now I just with the supplement side of it I'm just we're just not on the same page and I just have to leave it at that because I know of two cases where it's reoccurred and it's one thing now I'm just they all feel amazing because they're on these infusions and he goes through their bloods after but it's all during their chemotherapy and it just makes me very nervous now I think it's something that we have to Yeah, I don't know. IVT is very different. So glutathione is obviously we know what the issue is around there because it can engender some chemotherapy resistance and there is some preliminary data for that. And we just don't have safety data for it. It's still really popular in the US and a few other places. But IVC is a bit different. IVC at the doses that we give, so high dose IVC. Now, again, they might be giving different doses down where you are. I do give high dose IVC. And that means we usually starting from 25 grams and escalating to between 50 to 75. At that dose, it is not an antioxidant. It is a pro-oxidant. Really important to understand the mechanism of action. Oral vitamin C is an antioxidant. 50 grams has a pro-oxidant response. It has a tetanzyme action. It has about a million other actions. Just pop med it and have a little haplopathy. But it's a very different mechanism of action. So it's not your 500 milligrams, one gram, two grams orally, nothing like that. So I do give it alongside chemotherapy because it's pro-oxidant, but it's also anti-inflammatory. So you retain the anti-inflammatory action, but you also give a pro-oxidant effect. And there's certain studies around some specific cancers and cancer subtypes including bras and rap mutations that people find a particularly useful force that actually can improve clinical outcomes when given alongside all of the normal standard of care treatment um so i don't use them i do but not with them i just don't touch it it's just doesn't make any sense to me but there's also people who decide they're going to put glutathione in together with an ivc on back to back or even in the same bag and i'm like You're giving an antioxidant and a pro-oxidant in the same bag. Why? Why are you trying to knock off all of the effect of IVC with glutathione? It's just people who don't understand the mechanisms are trying to do it because somebody said somewhere at some training course that it was a fabulous idea. so yeah he's doing the two together i don't know she just gave me the list and i don't know if it all goes it just makes it i'm sorry like would you give a proxy and then two oxygen together randomly and would you expect the same clinical effect from a proxied no because you've just knocked off half of its effective antioxidant so it's just it if you're going to give something you need to know the mechanism actually to know what you're trying to do here and half the time it's not used appropriately for patients but lots of different effusions you know And misothrotherapy is another one which is when it's used appropriately, it's great. When it's used inappropriately, it can drive some significant side effects for people. So it's yeah, it's just everything has to be done with good training and a good, personalised way of approaching it. Cool. Good stuff. Thank you. Can I just quickly ask, where are the recordings of these Q&A sessions held? They are within the modules. It's usually one of the last ones on the pamphlet. So for the moment, this one isn't there, obviously, but you usually have a look at the previous module. This should be one of the last sessions. Can I start? I noticed on the supplement plan where it says the melatonin and then it says 60 and I know on the document you said 60 but it just randomly says 200. What does that mean? Well, she has 200 capsules of it. It's her supply. It's how much she has of it. Don't worry about it. Okay, okay. Thank you. I cut it off where it says capsules. 5.1 Managing Metastatic Cancer and Clinical Trials shown working with metastatic cancer and clinical trials. So in terms of metastatic cancer, it usually requires systemic therapy according to the different tumour types and the guidelines that currently exist in different local areas. It might include oral or intravenous chemotherapy, the usual regimes that we're used to. or targeted agents, it may be continuous or have treatment breaks. And switching of therapy usually occurs at disease progression. So the patient's usually monitored via regular scans and with or without treatment. markers depending on the different tumour types and if it's noted that the disease is no longer stable and the tumour might have grown over 30% or there might be new spread to different sites then usually the therapy is switched to the next line. New symptoms at any point with someone with known metastatic disease or someone who's previously had a significant high-risk tumour must be notified to the treatment team because that might indicate progression or new body sites involved. So for example, if we know we have a triple negative breast cancer or a non-small cell lung cancer and someone's starting to report morning headaches, they absolutely need to discuss it with their treatment team because it could be an indication of new brain metastases. Apart from systemic therapies, there may be other therapies involved in palliative management or other management of metastatic cancer such as palliative radiotherapy for spinal or brain metastases. Surgery is appropriate with the aim of debulking. You might want to treat the locally advanced cancer or you might want to just debulk the tumour, reduce its size to be able to make it a bit more manageable. It might be surgery for symptom control or treatment of life-threatening complications, for example, intestinal obstruction with GI cancers. different symptoms that might occur metastatic cancer but there's a few here that you might want to take note of so for example pain and swelling in different nodes these are specific for breast cancer but any pain and swelling in the lymph node should be reported to health care practitioner pain in bones in keeping out of patients usual pains without any trauma In terms of liver, people might notice they might have abdominal pain, particularly in the right upper quadrant, may have early satiety, or they might feel an enlarged liver, particularly when the doctor feels the abdomen. In terms of lungs, shortness of breath and persistent cough are really, really key red flags for us to look at. And of course, any blood anywhere, whether it's in stool, whether it is in sputum or needs to be reported to the healthcare practitioner. And as I mentioned with brain dust, there's quite a significant morning headaches and vomiting or any new onset neurological symptoms should be investigated. There are various guidelines, I'm obviously not going to talk you through all those in detail, but just so you know, when someone is diagnosed with advanced cancer, they go through this stepwise guideline from the medical front to ensure they get the therapy according to the specific guidelines. So for example, here if you've got locally advanced breast cancer, they might think about what type you've got and then either give you endocrine therapy, so it's hormone therapy if you're hormone positive, or chemotherapy if you're usually hormone negative. They might add anti-HER2 therapy if you're HER2 positive. And then effectively, there might be other things like operative management and radiotherapy as well. And then again, this is a triple negative, which is approached slightly differently. Again, you will see immunotherapy here. So that's anti-PD-L1 therapies here will come in relatively high up the treatment path. PARP inhibitors and those are BRCA mutations and the various different chemotherapy therapies are beyond the standard anthracycline, for example, or taxane-based treatment. So that's your ECT or ACT, for example. You might be looking at platinum-based, teriobulin, vinerilbin, or oracapisitabine, for example. For colorectal cancer, again, it's just an example. Again, you can see that it's subclassified by the different kinds of molecular profiles, whether they're Ras-WAL type or they might be BRAF mutant or Ras mutant, in which case they're given different therapies. according to that particular subtype. And again, as I said, we just then re-evaluate and use second-line or third-line regimes by the time that we get through that treatment path. And Bevacizumab is a name you might recognise. It's an anti-VEGF monoclonal antibody. Common name is Avastin. And again, it's quite commonly used as an additive therapy in terms of targeted medication alongside the chemotherapy double or triple therapy, depending on what the client with colorectal cancer has. I just want to talk you through an example of an oral chemotherapy drug, because, of course, we have talked through the IV chemotherapies before and some of the side effects and their potential management. Capicitabine is a relatively common oral chemotherapy drug. It generates 5-FU in the body, so it's 5-fluorouracil. And you can find out more information on the link here. It carries all the usual chemotherapy side effects, because effectively it's a precursor to 5-FU, but also carries hunt. foot syndrome risk and I'm sorry I misspelled that one. In terms of managing side effects oncology consideration of lowering dose is important because sometimes the dose is just too high for the client to handle and their topical recommendations while it might be useful so just keeping hands and feet cool and dry and considering 10% urea cream or lotion below. Thank you. Of course, in metastatic cancer, the other things we might want to be thinking about, particularly metastatic cancer, because we can have access to liquid biopsies in terms of circulating tumour DNA or circulating tumour cells in the bloodstream, we might consider precision and cordial as an emerging approach. And the premise of this approach is to develop treatments that target the molecular characteristics of the individual tumour. And actually, we might not want to treat colorectal cancer different to breast cancer if they've got the similar molecular. molecular profile, for example. So it's quite an interesting concept about actually having a look at which mutations and what molecular profile the tumour has and then treating it according to that and according to the driver pathways within that particular tumour. And that allows us more precision targeting because we're not assuming that the same pathway is active in one person's colorectal cancer is the same as the other person. We're being very targeted in what we are trying to achieve. And of course, with increasing availability availability of various genomic techniques such as next generation sequencing, the routine analysis of advanced cancers is feasible. We can analyse the actual biopsy sample or the tumour when it's removed and we can also get liquid biopsies just from a simple blood test. And as I said in the precision cordial approach the treatment selection will be guided by the molecular characteristics of the tumour. It's a really exciting and emerging approach but unfortunately we have much poorer access to it in the UK versus the US. because also in the NHS in terms of funding there's very little access for this sort of technology. Whereas in the US for example there are a number of liquid biopsies such as Gardend available on Medicare. So let's think about liquid biopsies. Obviously they're the medical only test. It's important that non-medics don't really have access to that. And there are a couple of different companies listed above, such as Data, Foundation Medicine, Gardened, and Oncologica, and there are many, many more providers within this area. But they are the four that I work with mostly and I understand the most. And they also are the ones that are most often used by oncologists in the UK versus the US. So why do this expensive liquid biopsy test? Because some of them range from anything between, you know, £1,500, £1,700 to over £3,000. It is reimbursed by some private insurance. Bupa is relatively good with that. There are some insurance that still don't reimburse any of those tests, such as AXA. But we hope the situation might change in the future. But why do it? So. I think it's important for us to think about when we are looking at metastatic cancer, this might particularly look at where we've come to the end of the line with current treatments or where the treatment has unacceptable toxicity. And the molecular profiling might give us access to personalized treatments and trials as well. So here are some of the example reports that come out of those liquid biopsies, which are a simple blood draw of several tubes. And so, for example, here you might see ESR1 mutations, which will lead the oncologist to think that this patient is going to be resistant to the vomitation. These inhibitors that might be on, and you can see there's actually a bracket 2 mutation showing up that will need to be confirmed by different tests because this patient might have a germline bracket 2 that might not have been detected before as well. Data Exacto, for example, has a slightly different format. It will actually, based on the molecular profile recommends and the standard of care therapies and off-label therapies, for example, it will highlight particular mutations that might have come up in the tumour, as well as looking at what's called chemo scales, that's chemo sensitivity scale. Now, I would take that one with a pinch of salt as an integrative doctor who works with oncologists because And normally it's only particularly useful to say which drugs are very unlikely to work rather than which drugs will work, because, of course, this is done in vitro in a cell culture. So you've got to remember that this is. not the actual full person. There are many, many different predictors of response to chemotherapy. But we can see if something like cisplatin and venerealbin are killing less than 25% of cells, they're pretty unlikely to be effective in a human being as well. Data and a few other liquid biopsies might also offer some non-conventional drugs, natural agents for looking at chemosensitivity and also looking at some of the pathways. So you have some examples here. And what's really useful is that some of these tests also run pharmacogenetics. So you can actually see which drugs you might have increased risk of toxicity with. And again, this is where an integrative doctor like me would, I would liaise with the oncologist or the oncologist themselves would consider what kind of dosing they might want to start this particular patient on because they might require dose adjustment. So how can nutrition integrative oncology help with within precision oncology really? And of course we have a role in helping to manage side effects from targeted therapies as well as looking at potentially improving outcomes managing multi-drug resistance and in the future we have a role in helping to manage side effects from targeted therapies future as we develop the data around this, potentially looking at treatment synergies. Of course, we've discussed immunotherapy of the gut microbiome previously, so I'm not going to go over that in detail again. We also need to consider that what's really exciting is there might be potential reasons. research for specific targets that get spat out by these reports that we don't have a drug against. So actually, where oncologists then consider it not actionable, well, actually, it might not be actionable in the pharmaceutical world, but there might be nutraceuticals or other strategies that we might be able to use to hit those targets in a different way. So for example, the wind beta-catenin pathway has been shown to be affected by question to a significant degree, and we should actually be looking at doing combination trials. for patients who exhibit this kind of upregulation of this pathway alongside other therapies and see if we can improve outcomes by synergy without adding toxicity. So think about managing side effects. Here's an example of... you know, using something for TKI, so tyrosine kinase inhibitor lopatinib. And this particular study showed that actually delivering it instead of at bedtime, but actually after an overnight fast can actually reduce toxicity from lopatinib in terms of reducing risk of diarrhea or rash without diminishing any therapeutic effect. And actually going broader beyond this, we know that animal studies show that fasting actually increases the ability of the common TKIs to block cancer cell growth and inhibit the map kinase signaling pathways. So again, it might not only be... reduction toxicity with fasting and something like lopatinib, but there might potentially be a treatment synergy. Another thing here, again, PI3 kinase inhibitors and ketogenic diets, so very low carbohydrate diets, it's important to remember that actually when you administer PI3K inhibitor, it will push up your blood glucose. So this hyperglycemia is a common adverse event which can impair treatment efficacy and increase the rate of treatment delays and discontinuation. And actually, while the mitra and triglyceride was metformin, using ketogenic diets to decrease the amount of dietary glucose actually entering the body, as well as using something called slip. SGLT2 inhibitors, and that's drugs like canagliflozin, can be really effective in managing that effect. And we also know that animal studies show there's a better response to PI3K inhibitors in terms of tumor response with ketogenic diets. So something to certainly consider in this setting. In terms of metastatic cancer, we need to think about palliative care. Palliative care doesn't always have to be end-of-life, it's a bit of a misconception. The earlier the palliative care team is involved in metastatic cases, the better, because actually they can provide ongoing care and access for clients and their carers for many months. And the benefits of early palliative care from research may include improved quality of life, potential benefit on depression, although not all studies show that, and enhanced coping. And it's really important for clients to have open and honest conversations and make their end-of-life preferences known to their team. Palliative care team members might include doctors including palliative care consultants and GPs, nurses, hospice and social care staff, chaplains of all faiths or none at all, physiotherapists, occupational therapists or complementary care as well. So it's important to think about palliative care is not necessary as an end-of-life intervention. It's a multidisciplinary support network for clients who have a metastatic diagnosis. So in terms of common concerns and really advanced cancer and they include pain, unsurprisingly mental health is affected with depression, anxiety, fatigue, weakness, loss of appetite, weight changes quite often with potentially significant weight loss due to cachexia and some tumours, nausea, vomiting, constipation and where there is an aspect of liver failure there can be abdominal swelling due to ascites that may require drainage. and patients can also suffer from shortness of breath and pleural effusions. I mean, there are many, many more concerns in advanced cancer, but they're just a few. And there are a number of different medications. The most common you will encounter would be pain relief medications, including opiates. And of course, here constipation is very common and can be very distressing for the patient to have that on top of their pain. And it's quite often used in the case of cancer. given with laxatives such as Mavacol and we know we can also provide other bowel support from our side. Steroids can be essential where there is brain swelling but they might be often used for other indications so we might see them used for what's called encouraging appetite but actually I'm very concerned about the system's impact of this because steroids will engender a certain degree of insulin resistance and will also suppress your immunity so if In terms of your overall impact on your ability to live with your cancers, it's going to have a significantly detrimental effect. And to be honest, they're clinically not particularly effective from that perspective anyway. They're often given with PPE. such as omeprazole and zoprazole if high dose steroids are given or there's longer term use. And of course, it has a further knock on effect on the gut. Antimetics or sort of anti-nausea medications are common. There's various different types of it. each with their own side effect and then many many more and when you have a client who has metastatic cancer and all is in all of these medications well worth having a look at the side effects on the british national formulary website just so you can be familiar with those when um clients reach the end of life and they might not be able to comply with or be willing to take medication orally or just for their comfort and a syringe driver may be issue to them to help with their symptoms. And that's basically a syringe of medications that has a tiny subcutaneous needle that basically gets put into the patient and it avoids the use of lots of oral medications and problems with swallowing. And some of the most common medications that are used. with the opiates for pain, antispasmodics such as hyacinth, and anti-nausea drugs as you can see, cyclosine, midaclopramide, levomipromazine, some for agitation, some anti-secretion medications, and that will very much depend on what the needs are as assessed by the palliative care team. So let's cover one of the really important aspects of working within the cancer field, and that's self-care for the practitioner. And if you work in this field, you need to make peace with the idea of your clients might not get better. Unlike nutritional therapists who might work with IBS or might work with early diabetes or other problems, our clients have a significant life limiting illness quite often. And we need to make peace with them dying and the lack of control that you might have over the case as well. Not to mention that our control is mainly illusory anyway. But it's important to think that offering compassion Passionate support and supporting quality of life of your client no matter where they are on the cancer trajectory is incredibly valuable work. But it can be exhausting. And you need to build in your own self-care practices. So look after your own foundations of nutrition, mood, and health. movement, sleep and stress management, you've got to walk your talk. And you need to include mind-body practices, time in nature, time to yourself and time with loved ones to be able to make sure that you can be effective as a healthcare practitioner. because you need to have a topped up tank to be able to truly exhibit a compassionate and detail-oriented and open attitude to bring to your clients' cases, which is what's required in our field. And do share with your community. And that's partially where the membership schemes in terms of mentorship are really useful. with certainly hope that as you progress through the mentorships that are starting later on, that you will be able to share your troubles and your difficulties with us and we'll be able to support you as a community. So we've covered a little bit about working with clients with metastatic cancer diagnosis. Let's move on now to working with clients on clinical trials. So just a quick introduction to the clinical trial phases. So in terms of medication development, it all starts with lab studies. And there are many, many medications that fail at that particular level. And in each step, you will know that there will be a proportion of medications that fail, which is very, very costly to do. to the companies that run these trials. Once you move past the laboratory studies, you might want to do a phase one trial, which lasts just several months, and just evaluate safety, and gathers really basic information about how the drug actually interacts with the human body. You might move on to a phase two trial, which is safety and dosing, and that's really quite often given at different doses of the medication and monitored for side effects, checking which dose works best, and whether it's actually a effective for the indication. And then phase three are the biggest trials. They're the most costly ones and can run for several years. It really is confirming effectiveness quite often. In cancer, they are evaluated against standard of care. So we're not going to run a placebo controlled trial in a cancer setting quite often because it's unethical. It's unethical to not give someone treatment for their cancer. But what we might want to run a trial against is to run a phase three trial of a new intervention versus standard of care and see which one comes up tops. And then once the approval has been received, so in the US it's the FDA, in the EU it's the MHRA, for example, then you enter the phase four, which is post-marketing surveillance. So this is where, again, some of the yellow card information goes. So this is just gathering information that drugs affect in different populations and any other side effects, particularly the ones associated with long term use, which you're not going to get out of a phase three trial. There are also very different trial designs in precision oncology, which is quite fascinating. So they're called umbrella and basket trials. So an umbrella trial takes the tumours of the same type. So let's just say colorectal cancer. And then you will actually put them in different categories. according to gene mutations. So for example, you will be a Ras-Weld type or Ras mutant, and it would give them different treatment according to the different gene mutations, which is really provided by the molecular analysis of the tumour. And a basket trial is something different. Instead of taking tumours of the same type, you're taking all the different tumours that share the same mutation of biomarker. So, for example, you might look at a HER2 inhibitor that will take not just breast cancers, but other solid tumours with HER2 markers and then put them all in the same trial and give them this particular treatment and see what comes out. So again, they're quite different because they're based on... a specific mutation biomarker. So what are the general pros and cons of being in a trial? I think it's really important overall to think about that beyond molecular oncology trials, beyond precision oncology trials, actually, most of the time, they... patients who participate in a cancer trial, the benefit is not necessarily to them per se it's to the cancer community because we don't know what the individual benefit might be and so the pros of being in a cancer trial they might receive state of the art treatment and it's a careful design Find a defined treatment protocol, there might be a potential for improved outcome, and there might be an innovative treatment approach and access to it, and might give patients hope, of course, and provide the benefits for them. the cancer community as a whole. In terms of cons, of course, because the therapy in phase three trials is selected by chance, it may or may not be the correct therapy for that particular patient. The patient does feel a bit like a guinea pig. In phase one, so the very early trials, the benefits and toxicities of treatment are unknown. And even in phase two trials, you don't know whether the dose you're going to be receiving in a phase two trial is going to be particularly toxic or not enough to actually experience any benefit. And of course, there might be potential for excessive or unknown toxicity from experimental therapy. And there's a lot of investment. There's definitely greater time and effort involved for both the patient and their carers. There's more testing, there's more monitoring compared to the standard treatment programs. And there might be travel required depending on where this clinical trial is being run. The usual clinical trial requirements include strict entry and exclusion criteria, so they'll have a two list of who's allowed in, who's not going to be allowed in, and as I said precision oncology trials will require molecular profiling for the entry. There is careful documentation of all medication supplements because of course they might affect the trial outcome and usually clients would be advised to stop all supplements but continue with their essential medications. So exceptions might be made. for some supplements in agreement with the trial team. So for example, vitamin D tends to be quite neutral. And actually, the trial team doesn't often discontinue that. And of course, often nutrients classed as medicines on the BNF are allowed. So if someone's on Atkal, for example, or another supplement that is classed as a medicine, then they might not be removed. There's a regular schedule for monitoring, including different blood tests and scans. and quite often scans are much more frequent than standard of care which can result in significantly increased exposure if the scans are radiation based such as CT or CT-PET for example and of course even with MRIs you're looking at contrast there. So we've got to think about just how much exposure, just how much more body load someone might have as well. And for the individual, the trial might be terminated on disease progression, but overall trials might be terminated as a whole if there are significantly better or significantly worse results of standard care being seen. And that's really from the safety perspective. And we've got to remember that with new medications that haven't been trialled properly, no one may know the full side effects or the interactions properly in the early trial phases. So it is a complete unknown for everybody involved. So what do clinical trials often measure and report on? So when you read the papers, what might you be able to see as outcome measures that you might want to look out for? So they might report overall survival rates. So for example, one-year survival or two-year survival. or five-year survival. And that's the percentage of people with a specific cancer type who will be alive at a certain time after diagnosis. There might be disease-free survival rate, and they are the patients who will remain in complete remission after finishing treatment for... however many years we're looking at. And then there's a progression-free survival rate. And that's really looking at people whose disease might have responded to treatment, either completely or partially, or completely stable. So cancer is there. They're not disease free, but they're not progressing. And so that's important for you to realise when you read a paper on interventions in cancer. You need to think about these different statistics and what they actually mean. So as a summary, in terms of working with metastatic cancer, because of the multiple treatment rounds that are quite often required as well as scans and waiting for news, supporting resilience is absolutely essential through these different rounds of treatment and ups and downs of disease. stability and progression. And that's the reality. The reality is metastatic cancer is a big, big roller coaster. And it's really important never to become complacent and also to really look after that psychomotor. of well-being and the HPA axis through all of this. Oral chemotherapy or oral targeted drugs may be used, as well as standard IV chemotherapy regimes, radiotherapy, surgery, IV infusions of targeted drugs, and there's a whole gamut of options. Precision coaching does have the potential to transform cancer care into a truly personalized paradigm that might move us finally past this all days of sequential chemotherapy rights for our medicine. to start clients, but the real thing is, Research is still ongoing and the access to liquid biopsies can be poor in the UK unless you have private insurance of the right kind really and an oncologist who is willing to do the test. Working with a client in a clinical trial, you really need to make sure that all interventions are notified to the trial team and do stick to nutrition lifestyle whenever possible instead of making things complicated. But be aware that side effects interactions may not be well described in trials. new medications. And so it's important for you to have a really careful and well-documented approach when you're working with someone in a clinical trial. Thank you very much for listening and the usual references. 5.2 Comprehensive Strategies for Cancer Recovery to systems approach to cancer. We're going to be talking about supporting recovery and resilience post treatment. Usual disclaimer. So what happens after you have finished with curative treatment on the NHS. So previously quite often um the client would be asked to go and attend for annual checks and they may have associated scans or other imaging but often little or no blood tests apart from hematological cancers that do get regular blood tests but now more organizations are converting to what's called patient triggered follow-up or PDOA patient directed open access and there are a couple of examples here on the PDF um about the how these programs work. But the overarching principle is instead of having an arbitrary date set for your annual check, you actually trigger your own follow-up if you have any concerns or questions or new symptoms. Um, and the idea of it is to really tailor the usage of the medical service and for people to be able to have easier access when they really do need it. In terms of the general approach, the foundations um for prevention in terms of cancer recurrence risk are completely appropriate um to take some of those from the general cancer prevention, what's called primary prevention. So primary prevention is where you're trying to prevent the problem from occurring in the first place. So primary prevention of cancer is the stuff that we talked about much earlier in the course. Secondary prevention is when you're trying to um prevent you know progression or other problems with disease. So we are thinking here specifically about minimizing recurrence risk in terms of cancer and WCRF says that all the appropriate measures that we talked about for cancer prevention they're appropriate here and I would agree to a certain extent. I think that from the nutrition perspective, we know there's been a number of large meta analyses that show that a whole foodbased diet rich in vegetables and fish were associated with um less overall mortality and things that were associated with increased mortality are things like higher al alcohol intake and the western dietary pattern. So actually having the what's called the prudent or healthy dietary pattern does make a difference in terms of overall mortality for cancer survivors. Um when you look at specific cancers the um the findings can be a bit more difficult to discern or interpret depending on the different approach because not all of them have um you know really large trials or large meta analyses. for colorctal cancer. There's been a review um of a number of different trials and it again says that colorectal cancer prognosis um in survivors appears to be worse with uh increased inactivity, smoking or being underweight after your diagnosis. So again, correcting weight back to normal is really important. And then there's emerging evidence um that diets associated with things like sugar consumption can potentially negatively impact survival. There was a 2021 review on prostate cancer that talked about smoking and consumption of highfat dairy being associated with high risk of recurrence and mortality and protective factors include physical activity and half to one glass of red wine a day and the glass means a small glass. It is really important particularly with prostate cancer but actually across the board that we need to think about including racially and ethnically diverse groups in research because a number of um this research has not been done in um for example black and Asian minority communities and we know that particularly for prostate cancer um these are the groups of people that can suffer from much more aggressive prostate cancer. So it's important to include those group groups in research and then thinking about again the dietary inflammatory index um and the anti-inflammatory diet that ultimately if you have a higher dietary inflammatory index is associated with increased risk of cancer recurrence um and the authors from this particular paper concluded that anti-inflammatory diets might decrease the risk and overall mortality uh particularly in those with kind of um different prognostic factors such as younger age, permenopausal women, people with hormone receptor positive breast cancer, larger tumor sizes and lymph node metastasis or those with obesity. So I'm going to give you again my slide on cancer prevention recommendation that includes recurrence from my side. So we know the core components anti-inflammatory Mediterranean style rainbow diet 7 10 portions of veg one two portions of low sugar fruit daily ideally making sure the berries forms at least one of those portions with the emphasis on cruciferous alien family vegetables mushrooms berries herbs and spices uh organic whenever possible healthy fats limiting red meat no more than twice a week and no processed red meat um overall um and if eating grains, of course, making them whole grains and vastly outweighed by vegetables and limiting dairy to organic fermented unsweetened forms and certainly within prostate cancer, I would um avoid all highfat dairy and ideally all dairy altogether. Overnight fasting of 13 to 14 hours is important and we've seen some of the um impact of um that on breast cancer although not all cancer types have been covered in research. No smoking, reducing, avoiding alcohol, no very little refined sugar, no processed foods, avoiding processed and refined oils and excessive sun exposure. Adequate hydration. Um, again considering other things like green tea or herbal teas and coffee in limited amounts. Moving regularly, really important to have that balance of aerobic strength and flexibility activities and for all the population balance work is really important as well. managing stress, getting adequate good quality sleep, healthy weight and body composition, reducing environmental exposures as we talked about before. And then the last bit that's my own little nugget um apart from the the um more general aspects is really just to follow personalized recommendations based on your own unique neutrogenetic background clinical history because we need to understand the drivers so we can manage the drivers. Then fasting recurrence risk in breast cancer. As I said, there's not been a lot of prolonged overnight fasting work done in other cancers because people have focused on quite specific regimes around chemotherapy or maybe using fasting mimicking diets. But we can see that fasting um less than 13 hours was associated with increase in breast cancer recurrence and you can see the the difference is about 36%. So then nightly fasting uh was actually not associated with any difference in breast cancer mortality or or cause mortality. So what it seemed to do is that fasting for a minimum of 13 hours tends to decrease your risk of breast cancer recurrence but may not affect mortality. But what it did affect is actually decreasing your HBA1C levels and having an effect on duration of nighttime sleep as well. So sleep is important. It's affected by of course the psychotional well-being and some of the medications people might be on particularly the ones that might disrupt um um the hormonal regulation and sleeping 7 to 8 hours can be important and particularly in breast cancer because that's where the studies have been done but of course it's likely to um be relevant for a wide range of people. We just need to do more research. It's important to not exceed 9 hours. So sleeping over 9 hours a night has been associated a 48% increased risk of breast cancer recurrence. So it's it's really important and a 52% increased risk of breast cancer specific mortality. And of course why do women sleep more than 9 hours post diagnosis? Well they might have um regular sleep difficulties for example or they might have um you know you might have poor quality sleep. So what we don't know necessarily is it just the sleep itself. So having kind of excessive sleep is that just a marker for having poor quality sleep or other problems with your sleep that lead you to sleep longer rather than the the excessive sleep itself. And I certainly wouldn't sleep under 7 hours as well because the sleep and cancer risk overall is a U-shaped curve where too little or too much are both dangerous and we need to stick to the sweet spot. terms of sleep support for cancer survivors, you might consider CBTI. So that's a specific CBT technique for insomnia. MBCTI, that's mindfulness-based interventions, yoga. Um, there's good evidence for mindfulness interventions and evidence for yoga in that setting. Exercise might also improve sleep quality. And of course, there's other more general support interventions, not all of them have been studied in in cancer survivors, that might include supplementation, herbal medicine. So evaluate and assess and support on a case-byase basis. Terms of stress management, psych emotional well-being, it is really essential that we support um our clients in in having good emotional self-management. So do support them with building a good toolkit and being self-aware and using that toolkit as needed. Mindfulness-based approach have a really solid evidence-based in cancer survivors. So yoga, yoga therapy, MBSR, MBCT courses that are easily now accessible online are really highly useful clinically and should definitely be a part of your referral repertoire in terms of evidence-based practice. Vigorous exercise might also be helpful in terms of stress management. And of course we know that even though it has a stimulatory effect in the in the short terms actually helps us being able to work through some of the stresses um and is able to as long as it's not excessive help us manage our HPA axis and cortisol. And we actually could see that there's been good research that vigorous exercise have been associated with less psychological burden cognitive impairment in childhood cancer survivors. And there have been a number of um pieces of research on homebased exercise program improving psychological health not just in colctal cancer survivors. There have been other has been other research in lung cancer and other cancer types as well. Dealing with feelings post treatment is really important because quite often this is what happens. You finish treatment and then the support gets withdrawn and we'll see you in a year and then actually that's when all of that emotional stuff really hits the client. um and everybody expects them to be fine because you know you're cured. What what more could you possibly want? It's all over. Well, actually quite a lot of the time um a lot of clients will function um as you know through this kind of treadmill of just doing the hospital points just putting one foot in front of the other and it's only when they pause and think and let it really sink in that they really feel the brunt of the psychological impact. So, do be on the lookout for trauma, both childhood trauma because childhood trauma may predispose people at poor pain outcomes, for example, um and other long-term problems following cancer diagnosis and of course in treatment trauma. Um, and we know that that's not necessarily very well detected or managed because over a third of patients who experience PTSD during breast cancer treatment are still experiencing symptoms over four years following treatment. And sometimes it gets dismissed. So this is just your chemobrain or cancer related fatigue or chemol related fatigue etc. But and because people can present as just being fatigued and having what's called dissociative symptoms not being quite quite connected, not being quite sharp, not really feeling um engaged and actually that can also be a sign of trauma. It doesn't always have to be um as simple as that. So do be on the lookout for it and refer for assessment by a proper psychology professional. they must receive specific treatment. This isn't something that you can you can manage. And it's really important that we get on top of trauma as quickly as possible. And sometimes if people exhibit traumatic responses during treatment, I will get them to work with a psychologist doing kind of um trauma protocols as this is occurring because actually that research has shown that the earlier you start trauma protocols things like EMDR etc. um that actually the better the longerterm outcome is. So it's important it's a little bit like you know emotional first aid. It's really important if someone is being traumatized by the treatment or what's happening to them that we institute interventions as quickly as possible. Skxiety is very real and can be debilitating for people. So do offer them uh referrals for tools and techniques. So breath work, mindfulness, EFT, psychological therapy tools for example, you know where they they might want to do counseling which is very low intensity. they might need actual specific psychology input such as ACT or CFT. So these are acceptance and commitment therapy and compassion focused therapy both excellent approaches um to to use in this particular setting. So you know assess and and refer. There will be people who might just benefit from a bit of counseling but I find that with people with really significantly embedded stress and trauma they require proper treatment and and if it's trauma they will require a treatment from a trauma specialist not just a general um psychological support and that's not going to be effective. Uh this is a useful resource for dealing with feelings post treatment. a really um great book um for coping with feelings after cancer. So I would encourage you to read that yourself um and uh recommend it to your clients. So we talked about more about general support. So we covered thinking about nutrition, thinking about physical activity, sleep, psycho emotional management. So let's think about more specific stuff. We need to remember our assessment. So using this model, what did you write down for that client? What were the key anticedants and triggers? What are the key priorities from the systems approach model? What needs addressing? And that's really important. So from the personalized approach, you need to make sure you keep in mind the anticedants including valibate neutrogenetics as well as things like adverse childhood events. And you've got to manage those things long term. They are the things that predisposed this dysfunction in terms of occurring. So we must address those whenever possible. Might not change anything about their childhood trauma of course but we might be able to get them the support they need for the very first time in their life. Remove and manage triggers. So if you think some of the key triggers might be to do with environmental exposures or um other things that you might have found in the history or significant disbiosis and poor diet in terms of colorctal cancer then manage that because that's going to be important to not continue with um in terms of cancer recurrence risk and then manage the ink on the systems approach which areas require most work and are most relevant and that's going to be shifting and changing post treatment you know during During treatment, maybe you were particularly concerned about specific things in treatment, but actually following treatment, all of that ink will change slightly. You might have different priorities. But for example, if you're having post chemotherapy hypotoxicity, you might want to um do a program for for supporting detoxification. So using selomarin for example or schizandra um for a few months until the LFTs go back to normal. If the inflammatory markers or NLR neutrfil to lymphosy ratio is still raised several months after chemotherapy you've got to manage the immune system that's an abnormal immune system that requires us to actively manage that rather than leave it and of course assessing and managing the HPA access post treatment across the board is important and you might not be able to do the salivory cortisol etc on everybody but managing and supporting the HPA access post treatment is important for people who have gone through significant stress both physical and psychological. Do retest relevant markers post treatment where possible and managed accordingly. You might want to do just a basic panel if that's the most accessible. So full blood count, total counts, neutrfil to lymphosy ratio, PLR, LFTs, kidney function, feritin with other iron markers if anemic, but of course feritin might be raised as in terms of high inflammatory states. CRP. Ideally, we'd have the fancy stuff. So, highly sensitive CRP with ESR, but we might not be able to get that. So, at least some CRP will be useful. Vitamin D just at minimum. At minimum, we could normally ask the GP to to run those. You must test the thyroid if there's radiotherapy to the chest or neck that's been received. Really important. Number of women will present with new onet thyroid dysfunction following radiotherapy for breast cancer, for example. Do you consider new onset autoimmune disease if people are presenting with symptoms after imunotherapy completion? See for example a lot of my triple negatives breast cancers who are being treated with imunotherapy up front now um actually coming with um you know new onset Hashimoto thyroiditis or sugar's disease and other autoimmune diseases. So do be on the lookout. Post recovery is also a really good time to assess other relevant systems. So for example you know the GI system if you've got someone who's um for whom it is particularly relevant Dutch plus if you've got a hormonal driven problem oat as appropriate to the clinical situation. So do leave 8 weeks following active treatment before running those usually um you know things like chemotherapy you need to let the GI microbiome settle a little bit before testing it. With regard to Dutch and tmoxifen, I will show you a case with that. But they will often show elevated estrogen due to lack of negative feedback on the HPG access because remember the tmoxifen will is a selective estrogen receptor modulator will block the feedback on the pituitary. So it keeps shouting for estrogen to be made but the estrogen is not binding to its receptors properly because tmoxifen is in the way. So actually we have a lot of women walking around with really highly elevated estradiol levels in estrogen positive breast cancer with tmoxifen around persistent immune dysfunction really matters and that's what I'd like you to think about even if not you can get nothing else out of people apart from their NLR in terms of full blood count and CRP we've got to remember that needs management we need to get it particularly the NLR under two if we can or under 2.5 it is relevant because look at this num across a number of different cancers the systemic immune inflammation index or NLR is prognostically significant it's associated with poor disease-free survival or overall survival or recurrence free survival so it is absolutely important quite often you know again in conventional management we just look at it and go oh the full blood count is roughly normal and no one ever calculates that so I'd encourage enrage you to go with the evidence on this. There have been a number of trials on this now and actually manage that actively. If you've got an elevated NLR, you need to manage inflammation. You need to support specific immunity. Terms of dealing with long-term side effects from therapy. Again, we covered hormone therapy in module 2. But apart from managing symptoms from that, bone density is essential to maintain long term. And people may or may not be on bisphosphin treatment. As we know, recent evidence in breast cancer suggests that those with early breast cancer may not actually derived any particular benefit from being on bisphosphinates weightbearing excess is absolutely essential. Um so it's really important to do that and so strength training. Um and clients might need a dexa scan by their GP. Usually this should be done by oncology before instituting things like aromatase inhibitors as per nice recommendations and then usually at regular intervals through treatment. I wish I could tell you this is being done everywhere. It's not but it's something to keep in mind and again do have a look at that link about osteoporosis risk with hormone therapy and that's obviously not just relevant for for breast cancer it's also relevant for prostate etc. Dealing with other long-term effects. I mean there there's a huge amount of potential wide ranging long-term effects. Now I've listed a couple of different ones. So um late effects for um adult survivors and late effects for survivors of childhood cancer because they have slightly different impacts. And so again it's too much to cover in this particular module and do have a look at the evidence for each specific effect on on PubMed. And if there's specific late effects you want me to cover, again, do let me know and um on the Facebook group and we can look into doing a special session on that. Finally, do watch out for signs of spread. Sadly, for many patients who received supposedly curative treatments, um cancer might come back as metastatic. So, being aware, clients need to be aware of their body but without excessively self monitoring and it can be a really difficult balance to strike. and any new or ongoing symptoms in a cancer fiber must be reported to their GP and if needed oncology team access should be triggered. So it's very very important and shouldn't be dismissed. So persistent cough new onset morning headaches all of that needs to be checked out properly. So as a summary, the foundations of an anti-inflammatory phytonutrient-rich whole food-based diet, regular and varied physical activity, adequate good quality sleep, and stress management, psycho emotional well-being support are essential and are supported by evidence. Dealing with emotional impact of treatment is absolutely important. We need to build a toolkit for psych emotional resilience. Might consider mindfulness-based interventions, yoga and psychological approaches that play a really important role. Any self-management tools that the client enjoys that helps them engage with the soothing system like breath work or EFT, anything like that they can do for themselves is really important. Long-term side effects may need targeted management. And then from our perspective, it's thinking about beyond those foundations of general health. Actually, a really good personalized plan should include the management of antecedants, so neutrogenetics, early life trauma or ACEs, removing and managing the key triggers that you've identified through the history, and addressing the key areas that have lit up on the systems approach model. And the post- treatment testing appropriate to the person you are seeing definitely has a role in supporting recovery and managing long-term risk. And it's important to foster and encourage compassionate self-awareness without overvigilance and excessive anxiety. And if you're not sure how to do that, it's there's a couple of um resources that you might want to explore for yourself as well because I think it's important for us to to try out some of those tools or know how to safely refer for those tools and when they might be most appropriate to be of most service to the clients we work with. Thank you very much for listening and the usual reference is available. and then long-term 5.3 Case Study on Estrogen Positive Breast Cancer Hi everyone and welcome to the month five case study. So this is about a case of estrogen positive breast cancer. So we're going to start off with a bit about the test results that come from a different clinic and I'll give you a bit of background for this lady. So this was a 45year-old um female who came to see me following a diagnosis of estrogen positive breast cancer but she actually had some um test results done a couple of years beforehand at a different clinic. I just want to give you that as a little bit of background. And what you can see here is there was HPA axis dysfunction at that particular point. And she had a really difficult marriage that she um got out of over the course of that time and had a very acrimonious divorce unsurprisingly. And you can see really she's pushing her 3/4 to significant degree. Um, we also can note that there is elevated for hydroxyone on in the picture. So you can see that she's pushing the cip one B1 pathway to create more of those quinones, semiquinones that then can go on and um bind and damage DNA. And this wasn't really particularly well managed um from our perspective. Um in terms of um no mention was made of any kind of estrogen metabolis issues. Um she was put on a B complex given the markers of B12 and B6 deficiency. Um and there was a half-hearted attempt at adaptogens but really that was it. So overall the Dutch was not particularly well managed. You can also see at that point her pyrolutamates also above range. So again thinking about creating those kinos and not being able to detoxify them via glutathione pathways. That's really a recipe for problems downstream and melatonium was below range as well. So of course we know that melatonin plays a role in cancer pathogenicity cancer risk. So you can see a number of things stacking up here. HPA axis dysfunction, poor estrogen detoxification in terms of elevated for hydroxy metabolites and elevated paraglutamate indicating glutathione pathway dysfunction. You can see here obviously her methylation may may be affected with B6 and B12 markers being elevated and low melatonin. So a little bit unsurprisingly really in 2020 she was diagnosed with estrogen receptor positive breast cancer and has then undergone treatment. and she had a lumpctomy. She had nine uh sessions of pletaxel and then radiotherapy. And during chemotherapy, she was diagnosed with um what they labeled as fibromyalgia. There was a lot of body aches and pains and she was alsoing also suffering from from shoulder pain um which evolved into a frozen shoulder. So when I saw her um I had tests available um it was several months after her breast cancer diagnosis and treatment. She actually finished nine sessions of platit which they had to stop because her liver function um was going off. Um and so these tests were taken um about 2 3 months following her treatment. Um, in the meantime, in an attempt to get healthier, as quite often women do, um, she went completely um, vegan/plant-based and has, um, really converted to quite a high carbohydrate plant-based diet with very little by way of um, omega-3 fats um, and adequate protein. She was feeling absolutely exhausted. So when I saw the blood test of course you could see that her serum 13in is eight um and she wasn't menrating the time because um pitaxel has shut that down so her 13 was eight um you can see that her vitamin D wasn't adequate at 65 and her CRP is elevated at two but by elevated I mean not infection elevated but elevated in way of chronic inflammation. We want our CRP to be under one in terms of long-term inflammation control. Um, and you can see here ALT is still elevated even months after Pataxel has finished. She's got really poor corrected serum calcium levels. Um, liver function um is affected but kidney function is normal. In terms of full blood count, she wasn't anemic at the time. the ESR was normal, but her RDW, so that's red blood cell distribution width was affected at 14.3. Um, and you can also see that the lymphosy count is still low. So there's poor recovery following chemotherapy and an elevated neutrfil to lymphosy ratio. So she undergone some immediate management from my side while we were running further testing and I basically put her on a anti-inflammatory wild fish pescatarian diet um low in sugar or basing all of her meals instead of on a high carbohydrate way around the PFC with at least two colors, plenty of herbs and spices, complete alcohol avoidance, um given both estrogen receptor positive breast cancer but also um borderline line elevated ALT that's persisting months after patitaxel and we talked about um relying much more on carbohydrates from vegetables rather than grains plenty of healthy fats again the sort of more Mediterranean style diet extra virgin olive oil is the main non-ooking oil avocado oil for cooking with limited amounts of um coconut for example at for higher temperature cooking wild small oily fish plenty of nuts and seed with mil flax and chia t two tablespoons a day. So, we we really tried to turn it into a a whole food from a whole food plant-based very high carbohydrate diet to a more balanced anti-inflammatory wild fish pescatarian and she absolutely noticed a huge difference in her energy after that. Um, we also talked about um you know continuing with walking. she was walking. Um but we added on some gentle mobilization, asked to do some strength work and get some advice on that. Um given her shoulder from an osteopath or a physiootherapist depending who was available um to her. We discussed stress management because she previously had problems um with the HBA access. And in terms of supplementation, we put her on uh uh cytoplan women's whole food multi um D3 and K2 highdose replacement. That's a seeking health and amita. Uh we u put on two biot essential to again support the gut microbiome health following chemotherapy. Um and increased antioxidant status. um increased RDW and absence of frankanemia quite often is an indicator of increased oxidative stress. So I wanted to make sure she was getting enough on board and we did replace her iron with a very short course of iron C. We uh also started on selarin rayi cord cheps and respirator extra particularly for the cip one B1 inhibition and I also got magnesium before bed she because she was having some trouble um with sleeping and also with the fact that she was experienced a lot of muscular tightness. So the results you see here are the results on these supplements and that's the second round really. Um, so you can see the HPA axis has changed. So it's no longer going going super high. Um, she's still kind of pushing the higher end of the metabolized cortisol. She has a poor waking cortisol and we remember that's not of course a great thing to have from our perspective. And she was struggling to get out of bed. So poor morning cortisol. You can see the the actually estrogen, progesterone looks okay. She's pushing her testosterone quite hard, but it's not aromatizing very well down to estrogen. Um, and you can see actually just by putting her on resveratrol, you can see how much that's dropped her full hydroxy estrone. So, that's now actually on the low end um and below the normal range. So, that's a significant improvement. You can see it was nearly double that um of respirator in the previous test. um she had she was slightly borderline on the B12. Again, that's probably a reflection of us still continuing the replacement after she went fully plant-based. And of course, all the increased requirements that she had for the B complex through both stress and of course treatment as well. Um and her melatonin was now within within normal range from that perspective. And uh her oxidative stress markers were normal. Of course we have to remember that 8 hydroxy deoxy guanosine is um really a mark of water soluble or antioxidant stat is not fat soluble and you can see their progress. So you can see I saw in September and then we reviewed in November and there was a significant drop in the MSQ from 73 to 46. It's a 56% reduction in then going on to January to 32 then. So it's it's we can make significant impact with the work that we do. Terms of um blood test progress uh we've outlined of course the September problems um in November her RDW was still mildly elevated and her lymphosy count was still um on the low side. Her NLR um was slightly better. Her ferotin went up from 8 to 18 but still needed improving. and her CRP has halved from two in September with dietary changes and supplements. Her LFTs were now normal um and but her borderline um low corrected calcium was was still a problem. So it increased um now to borderline from frankly low but we also increased non-dairy calcium rich foods and then in January 2021 all results were normal really at that point and the things that we did was that we I at the time when I saw her we um tweaked the multivitamin we started um two teaspoons of aex omega and that's omega3 with vitamin D and E. She continued buy me essential. We stopped the iron replacement because we only gave one bottle, but we aimed for plenty of dietary iron sources. She also took um thimulus and that's a a supplement I discussed with you back in module 2 and that um had a significant effect. You can see in January 2021 she had a normal white cell count with a normal NLR um you know down from 3.3 down to normal and then lymphosy count went up from 0.9 to normal uh to 1.2. Um she continued on um she continued on adrenal support we changed it slightly. So racial cord ships uh went on uh respirator continued um overall but I added some more HPX support with regard to that low morning cortisol. So we popped her on radiola complex um from that perspective. Uh she had um continue with magnesium and we also added some willow bark and biz will because she was getting more shoulder pain and inflammation. Um and we did a little bit of gut work as well. So really you can see a significant change. So by January your CRP is 6. It's perfect. It's decreased from two in September. ESI is normal. Normal white cell count normal NLR. TSH was slightly above optimal to84 but actually freeT3 and freeT4 were all normal. Normal tumor markers and feritin now 38 of all iron replacement. That's just dietary intervention. and LDH has been within normal range but has also decreased with normal liver function and normal corrected calcium. Um and then we did further testing and um uh really the there was only um minor tweaks based on that. So we could see the DNA health. We can see there was um a need for supporting methylation and you can see all of my notes here on that. Um and so we talked a bit about um choline. We talked about addressing adequate methyl folate. So at this point we tweaked the um um multi-nutrient because I needed to add a bit more methyl folate. So cytoplan has quite a good dose of methile B12 for example has a very poor dose of methylolate. Uh, of course the magnesium we already given as well as some the stress management advice that we talked about was also helping with a compa. Um, she was already on cruciferous vegetables. So that could help us with um, GSTM1 deletion in pair GSTP1. So really just what cruciferous veg do in that particular um, setting particularly broccoli sprouts which is what I usually recommend is they really upregulate the remaining GST enzymes. they can't give you a GSTM1 back, but of course they can upregulate the impaired GSTP one and support GST1 potentially. Um, we could also see that inflammation, oxidative stress, there were all three messengers affected. And of course, if we're having anti-inflammatory whole foodbased, high phytonutrient diet, which is what she was placed on at the point of entry into the program, then we know we're managing that. She had a high risk of insulin resistance. So you can see that actually um high carbohydrate plant-based diet wasn't going to be ever the right fit. You needed to balance that. If she wanted to continue to be plant-based, we would have tweaked um that as well. It's entirely possible to do so, but it's important that she wasn't high grain with that TCF7L2. And of course with PA gamma, that means um you've got to be looking at uh keeping your saturated fats low. um she had trouble with gluten in the gut before and certainly found it a bit a little bit trickier um following chemotherapy. So we just said keep gluten on the low side and I encourage her to only eat kind of um occasional amounts um in the best form possible. So maybe you know a little bit of whole grain spelt sourdough high need for preformed vitamin A again not available in plant-based diet. So it was important for us to have that in and again aex omega was quite helpful within that setting for us to continue with um high need of vitamin D to achieve adequate levels. So actually her maintenance um is higher than other people's maintenance. So I find that depending on the combination of C2R1 and GC snips, you might want to give people anything between sort of um 2 to 3,000 in summer if they're not getting out regularly and around about 5,000 in winter um in terms of I use vitamin D3. But of course it has to be adjusted to individual blood levels. Everybody slightly different and you do have to give a summer and a winter dose. So people who have significant impact on C2R1 and a GC snips, they're just not able to, you know, get 100 to 115 nanomals per liter, for example, um with um without any supplementation, particularly if they're working in jobs that have them hidden away in an office Monday to Friday 9 to5. And she also had a fat two snip. So again for her given her genotype really wildfish pescatarian diet um was was actually a better fit for her um in in terms of um fitting her neutrogenetics. And you can see actually she had a regulated production of sex hormones via cip 17a and you could see her pushing the testosterone and what we remember is actually the that um we reseratrol is excellent because it acts at certain different points in the pathway. Now rveratrol is not what I would choose to use long term if someone's got a double compted. So longterm the this at this point uh when I've managed the the higher testosterone um I would normally switch to transer still bean at that point um so between 50 to 100 millig um to be able to manage the cip 1 b1 without affecting but tp does not have the same effect on does not appear at the moment to have the same effect on cip 17a. Um and you can see that of course she was expressing an upregulated cip one B1 previously which we then managed with rveratrol. So a number of different areas that we covered and I said the only main tweak that we did from her perspective is actually making sure she's got adequate methile folate from our side and then long-term switch uh from resveratrol to transerous till bean so that we are still getting that sip 1 B1 inhibition without having impact on methylation and that's uh a little testimonial uh from client and I I do say that in in in in clients with locally contained cancers. My aim is to get um clients feeling better than they did before their cancer diagnosis. That's the aim of the game because you want to make sure that you rehab them to higher than their baseline to minimize the risk of cancer recurrence and I think we can absolutely do that. Thank you very much for listening.