Transcript for:
Understanding Metabolic Health with Dr. Casey Means

welcome to the huberman Lab podcast where we discuss science and science-based tools for everyday [Music] life I'm Andrew huberman and I'm a professor of neurobiology and Opthalmology at Stanford School of Medicine my guest today is Dr Casey means Dr Casey means did her undergraduate degree at Stanford University and her medical degree at Stanford University School of Medicine she is one of the world's foremost experts in metabolic Health today we discuss how metabolic function and dysfunction impacts our health in particular we discuss mitochondria which are involved in energy production within our cells and the various things that we can each and all do to ensure proper mitochondrial function which is essential not just for things like body composition and physical and mental energy but also our ability to regulate hormones blood sugar and much more we discuss how exercise even simple exercise like walking as well as sleep as well as more vigorous exercise and in particular nutrition including the types of foods we eat the timing of food intake and the sources and quality of those Foods impact are mitochondria and other aspects of metabolic function we also discuss how particular micronutrients within specific foods can directly impact mitochondrial and metabolic Health Dr means explains how mitochondria inflammation and reactive oxygen species which are the byproducts of metabolism in our cells can combine to create conditions of obesity as well as ways that we can manage those things or even reverse mitochondrial inflammation and reactive oxygen species dysfunction in order to reverse obesity reverse diabetes and enhance our health in Myriad Ways by the end of today's discussion you'll have a clear picture of the cellular processes that occur in the brain and body that underly metabolic disease and metabolic health and most importantly you'll have a very clear picture of the actionable items that we can each and all carry out every day and every week in order to ensure metabolic Health proper mitochondrial function and indeed that can also body composition and overall feelings of well-being I would also like to share that Dr Casey means has a terrific new book coming out I know it's terrific because I've read it it is entitled good energy the surprising connection between metabolism and Limitless Health if you're interested in the book we provided a link to the book in the show note captions before we begin I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford it is however part of my desire and effort to bring zero cost to Consumer information about science and science Rel tools to the general public in keeping with that theme I'd like to thank the sponsors of today's podcast our first sponsor is Maui Nei venon Maui Nei venison is the most nutrient-dense and delicious red meat available I've spoken before on this podcast and with several expert guests on this podcast about the fact that most of us 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coffee meaning no bitterness and excellent taste Aeropress achieves this because it uses a very short contact time between the hot water and the coffee and that short contact time also means that you can brew an excellent cup of coffee very quickly the whole thing takes only about 3 minutes I started using an aero press over 10 years ago and I learned about it from a guy named Alan Adler who's a former Stanford engineer who's also an inventor he developed things like the aobi Frisbee in any event I'm a big fan of Adler inventions and when I heard he developed a coffee maker the Aro press I tried it and I found that indeed it makes the best possible Tas in cup of coffee it's also extremely small and portable so I started using it in the laboratory when I travel on the road and also at home and I'm not alone in my love of the Aeropress coffee maker with over 55,000 f-star reviews Aeropress is the best reviewed coffee press in the world if you'd like to try Aeropress you can go to Aero press.com huberman to get 20% off Aeropress currently ships in the USA Canada and to over 60 other countries around the world again that's Aero press.com huberman and now for my discussion with Dr Casey means Dr Casey means welcome Dr Andrew hman thank you so much for having me really excited to talk to you today about all things Health one of the things I love so much about your work is that you really give people a sense of agency through knowledge and actionable tools which is very near and dear to my mission and my heart but to kick things off let's talk about metabolic function and dysfunction I think most people hear the word metabolism and they think okay the burning of energy maybe they think about ATP maybe they think about calories in calories out that sort of thing but what are we talking about when we're talking about metabolic function and dysfunction because these are really important concepts for everyone to understand yeah I think you're exactly right I think that when we hear the word metabolism the first thing that comes to most people's minds is my weight do I have a fast metabolism or do I have a slow metabolism or something like basil metabolic rate and I think what's really important for people to realize is that metabolism is actually the foundation of all Health it is the core foundational pathway that drives all other aspects of health and it's also the core foundational pathway that's truly getting crushed in the modern American World and underlying nine of the 10 leading causes of death in the United States today it's really quite relevant to everyone and the spectrum of metabolic rooted disease is vast and actually really relevant to most Americans the latest research from American College of Cardiology suggests that 93% of American adults have suboptimal metabolism and we can go into what that means but fundamentally when we're talking about metabolism we're talking about how we convert food energy to human energy so we take in a astonishing 70 metric tons or so of food in our lifetime and that is potential energy it's energy from the environment that's outside of us that through our metabolic pathways gets converted to a currency of energy that can then be used to pay for essentially Every chemical reaction inside our body and the bubbling up of all of those chemical reactions is our lives and so when metabolism is not working properly it's essentially creating underpowered cells and like any City or factory or machine not having adequate power will lead to dysfunction and the reason that the metabolic spectrum of disease is so vast is because we have over 200 cell types in the body and underpowering in different cell types is going to look like different symptoms because underpowering in a asite is going to look different than underpowering an ovarian thica cell or an endothelial cell it's going to look different but the core foundational process that is dysfunctional can actually be the same and I think the biggest blind spot in Western healthc care and actually the reason that Health outcomes are actually getting worse every year in the United States is because fundamentally we are ignoring metabolic health and metabolic dysfunction we are laser focused on the downstream symptoms that result from metabolic dysfunction in different cell types and we spend all of our energy uh focusing on those symptoms playing wacl with them and really ignoring that underlying foundational root cause of metabolic function and what's so fascinating to me and what I saw in the Health Care system as like a Super Subs specialist as an ENT surgeon is that you know the more we specialize in health care we have over a hundred Specialties now that we've just like invented in the Health Care System the more we specialize in health care the sicker we're actually getting so the more we do technological innovation in all these different Specialties the sicker we're getting and I think what what the real nugget there that that everyone really needs to understand is we've bought into a system where we value specialization and this is the game in Western medicine but while we've done that what has happened is we have the worst chronic disease epidemic and the lowest life expectancy of any High income country in the world and the reason is because in that specialization were focused on the downstream manifestation of underpowering of cells the the cell specific symptoms and not the metabolic function itself so really our chronic disease epidemic in this country it is a metabolic dysfunction epidemic and underpowering epidemic and that is the biggest blind spot in health care and I think a focus on metabolic function as the center of our health care System it's a completely new paradigm for health that is urgently and I cannot overs say it enough it's urgently needed we know we're not in the right Paradigm right now when we have a hundred isolated Specialties and yet 85 to 90% of the conditions in those Specialties if you go to the science and look at the real physiology is metabolic dysfunction so that's kind of the landscape of what metabolic dysfunction is and how it's kind of creating a a big blind spot in the Health Care system that really represents an outdated way of categorizing disease that unfortunately is killing us I would say yeah thank you for that I have um several Reflections and a question uh first off the the analogy that comes to mind is an assembly line that's constructing let's say an automobile and it sounds like 80 to 90% of the automobiles that are coming off that assembly line are not working well tires aren't on line engines isn't working well transmission isn't working a bunch of issues and no Factory no car manufacturer would tolerate that nor would the customers but we're tolerating that in ourselves it sounds like many people are and then accepting the fact that then a bunch of other businesses are going to crop up like the business that aligns the tires the business that goes and repairs the Pistons and and essentially when you talk about these multi Specialties that have evolved in the in the medical care system they provide an opportunity to go and fix the problems or try and ameliorate the problems but really what we need to do to make this analogy uh much briefer than it otherwise would be is just to go further up the assembly line figure out whether or not the hardware is correct the software is correct and where the hardware and software are becoming deficient in this um in this analogy where we are the automobile that's essentially coming off the conveyor broken and the good news is and I know this because I've read your book and because I follow your work very closely the good news is that we each and all can take matters to some extent into our own hands collaborate with healthc care providers yeah and repair metabolic dysfunction essentially make us metabolically functional so um the question therefore is I think most people when they hear metabolism they think energy yep and when we hear energy we think ATP sometimes but typically people think about mitochondria right the PowerHouse of the cell so to speak um so you've talked about the trifecta or the the big three mitochondria inflammation and oxidative stress as three critical factors underlying metabolic dysfunction and I'm presuming those are also the Avenues to address in order to create metabolic function because ultimately what we want of course is an optimistic picture that we can actually take some control that we have some agency in all of this which I believe we do so if you would could you get us all on the same page about you know what are mitochondria and what they do why are they so important then we can turn to inflammation and oxidative stress yes absolutely so the mitochondria or are the structure within the cells we have 40 trillion cells and each cell might have a handful or many thousand mitochondria and they are the magical part of the cell that does that conversion process of food breaking down uh and then converting to energy to translating it to a currency of energy our body can recognize and So currently what's happening is that our environment the environment that our cells exist in across every single facet of our life over the past 50 to 75 years has changed rapidly you look at how our food system has changed from whole real food in good soil to Industrial food our sleep habits have changed we're sleeping less it's very fragmented our movement patterns have changed we're sitting 80% of the waking day our time in nature has changed we actually are indoors As Americans 93% of a 24-hour periods that totally changes our relationship with light we have 80,000 synthetic toxins in our food water air personal care products home care products we live a Thermon neutral existence now with our thermostats there's no real swings in temperature unless you're in intentionally trying to um and then our emotional health is very different we are very much exposed to lowgrade chronic stress triggers so across food sleep movement emotional health toxins light and temperature things are not what they once were and it's changed in the blink of an eye I mean the light bulb was created in 1806 this is like 0.04% of human history that we' even had artificial light so things have changed and the the unique thing about all of these Chang in our environment is that each one of those pillars each of those changes in our environment synergistically directly hurts the mitochondria through different mechanisms The Chronic low-grade stress the sitting the ultr processed nutrient devoid food even the the blue light at nighttime all of it through different core biologic mechanisms synergistically hits this part of the cell the mitochondria so we have the food coming in but we're not doing a a job of converting it to an energy form we can use so we have these underpowered dysfunctional cells because of mitochondrial dysfunction caused by our environment and of course what happens if you've got energy substrate that you can't process it's going to be stored and that's of course why we have an obesity and overweight epidemic that's affecting close to 80% of American so wild it's it's just we talk about obesity like it's the problem obesity is one branch of a tree that that's rooted in this mitochondrial dysfunction that's caused by our environment and just to back up a little bit to just sort of share kind of maybe like how I sort of started thinking about that you know I I had trained as an ENT surgeon and I was at Stanford Medical School and I I was so fascinated by this idea of like the way that we're defining the diseases we're treating in these in in like a specialty like ENT is like I I saw sinusitis day in and day out and we'd have these patients on the table that we'd be literally drilling into their skulls to suck out sinus pus and that's like the treatment for sinusitis and the way we diagnose the patients is we say like okay this patient has sinusitis if they have facial pressure purulent pus you know nasal discharge um nasal obstruction and low sense of smell so if they have these symptoms then they have this disease but when you actually go to the science and you actually go to the studies of like what is actually happening to create this what you find is a lot of papers about mitochondrial dysfunction because Chron you know sinusitis is a chronic inflammatory condition where the cells are essentially sensing some threat and then they mount this immune response that creates swelling and then you get pus buildup but we confuse the the pus buildup with the disease which is actually happening inside the cells and so you start looking at PubMed as a as a clinician through a slightly different lens of like what's actually happening in the cells and what you find for almost every chronic disease we're seeing in the US is that you will find a lot of papers on how the mitochondria are dysfunctional lower ATP generation in a lot of these cell types and then what does that do and this gets your question about chronic inflammation oxa of stress well when you've got that dysfunctional mitochondria let's say in a nasal mucosal tissue that is a cell that can't do its job that is a cell that's underpowered and what could be more threatening to the body than a cell that can't do its job so interestingly those cells will initiate a whole process which is called the cell danger response um it's work that's been done by Robert navio at uh UCSD where basically they understand the mitochondria is not working properly this is of course caused by the environment and they will actually release extracellular ATP which is not really supposed to go outside of the cell and that creates a massive innate immune response saying like I'm underpowered I need help my mitochondria is broken this is the cell releases ATP outside of the cell usually the concentration of ATP is a million times higher inside the cell so releases it almost as a neurotransmitter a purogen neurotransmitter that massively activates the immune system to come and help but the immune system comes and is like not much we can do for you here because the problem is not something that the immune system can help with like grabbing a bacteria and licing it or you know taking care of some cells infected with a virus the problem is outside the body it's the environment so you end up getting this tornado of dysfunction of mitochondrial dysfunction caused by the environment leading to the cell danger response which leads to innate immunity and then on top of this you get the oxa of stress which is the third piece of the trifecta which is essentially these mitochondria trying so hard to do their work but they're not working properly so they create damaging metabolic byproducts called oxid of stress free radicals that cause more damage so this is happening in the nose it's happening all over the American Body because of our environment so you've got these tornadoes of interrelated physiology of mitochondrial dysfunction chronic inflammation oxidative stress which if you start going to the research as a clinician who's focused on symptoms and confusing those for the disease and look at what's the pathophysiology of arthritis what's the pathophysiology of Alzheimer's dementia what's the pathophysiology of type2 diabetes obesity fatter fatty liver disease polycystic ovarian syndrome erectile dysfunction it all traces back to this Trifecta that no medication or surgery you obviously can't operate on oxidative stress you can operate on the downstream symptoms so that's the real secret that I really feel like we need to reorient the Healthcare System around since 90% of health care costs go towards treating the downstream symptoms of these and for every marginal dollar we're spending on treating symptoms we're getting s the rates are going up because they're doing nothing to actually affect that Trifecta but to really make it simple I like to think of this Trifecta of what I call Trifecta of bad energy Trifecta underlying metabolic dysfunction of chronic inflammation mitochondrial dysfunction oxidative stress as chronic inflammation is biochemical fear its response to a threat mitochondrial dysfunction is kind of like rolling blackouts it's not enough power and the oxid of stress is like wildfires so it's kind of what's funny to me a little bit is like what's happening inside the cell is almost like what's happening like in our society it's like this is like living in California it's like blackouts fire fear and that's literally what's happening inside our cell because of the environment and uh again the optimistic news that you alluded to is that we actually have tons of tools and tests that can actually help us understand our level of metabolic health and even give us hints about inflammation oxidative stress and mitochondria dysfunction and it's very easy easy to improve if we know what we're actually focused on well that's reassuring and we're definitely going to go there um I appreciate the analogy to living in California I've lived here my entire life I have been outside of California but um perhaps the only thing you left out besides rolling blackouts fires and what was the other one fear and fear is high taxes the taxes the health debt on on the on the body so in any case not to be too dark and pessimistic well that's the healthare cost I maintain great hope and and still a lot of love for California you know pretty great it's got It's Great aspects and it's not so great aspects and I can say that as a lifelong California resident um there are other wonderful places to live a couple of uh questions first of all about places to live you've been talking a lot about in the United States are some of the same issues with metabolic dysfunction occurring outside of the United States I would imagine so y any country where we've exported the standard American diet and some of the other Norms of Western living are starting to see the same rat uh of of chronic disease but like it is worth not mincing words here of all high income countries in the world the United States has the worst chronic disease rates and the lowest life expectancy and our life expectancy is going down and we spend about twice as much on health care than the second highest spending country in the world so we are we are abjectly failing and that failure is predicated in our Cult of siloing conditions into different you know different Specialties and not focusing on this root cause and I want to just be super clear like there's a war being fought right now to get us to believe that siloing is the way because as you alluded to siloing is profitable if you can convince doctors and people that they 10 different symptoms are separate things then they're going to 10 different specialist office office meanwhile 75% of American adults are overweight and obese some of the highest in the world um a full 50% of American adults now have pre-diabetes and type 2 diabetes 50% 30% of teens have pre-diabetes 40% of Americans have a mental health diagnosis cancer is set to reach 2 million cases this year in 2024 highest ever in recorded history Alzheimer's is going up fat liver disease is affecting 40% of adults 18% of teens autoimmune diseases skyrocketing infertility is going up at huge rates all these things are going up all at once in the US and yes in many of the other countries that are eating our diet um and there's no sign of it slowing down and so that's really if you look at if you look at the research through this this different lens you'll find that all of those diseases Trace back to metabolic dysfunction caused by our environment that no that no shot pill or surgery can really address unless we unpack the environmental piece scary picture I'm glad that but hopeful but hope exactly I'm glad that you are um creating Solutions and and I should say and just remind people I said this in my introduction but you know you're talking about siloed medical care you're talking about the kind of standard medical system but let's not forget right um I happen to be a faculty at Stanford you did your medical training at Stanford are a medical doctor right I mean you have MD and are highly trained you were an ENT your nose and throat doctor so if anyone would be familiar with the industry and the practice and the educational system around this it's you so uh you're not speaking outside your bwick so before we pivot to Solutions yeah I know people are eager to hear Solutions but in order to understand how to best apply those Solutions I do think it's worth drilling into um some of the issues here just a little bit more you talked about underpowered cells yeah you've also alluded to the fact that most people are consuming enough and probably excess amounts of caloric energy yes so is it the lack of mitochondria or mitochondrial dysfunction that's at the root of the problem the analogy I come up with is you've got um a power plant that can convert incoming power line to um Power that can be distributed to a community yeah the community in this analogy being the organs and cells of the body yeah there's plenty of potential energy but there's something about the power plant that is inefficient or dysfunctional they shorts they circuitry that's just not working such that the energy that the community can benefit from the cells and organs of the body is just not there so it's not a lack of input it's a lack of conversion and output and the consequence of this we see in the form of excess adapost tissue and all the Downstream effects it's not just aesthetic it's really all the downstream effects of visceral fat subcutaneous fat Etc what is it that would improve access to energy and energy utilization in cells is it simply a matter of getting the mitochondria to function better or is it that one can actually create more mitochondria this is the key question for how we can get healthy and it's really about creating capacity in the body to turn more potential energy to usable energy as opposed to taking that potential energy and shunting it to a storage form it's all just like I think about everything visually and I'm like you got the circular cell from high school biology textbook inside are all the little mitochondria with the squiggly lines inside and it's just like there's X's through those mitochondria so instead of you know after glycolisis and you've got the pyate instead of going through the mitochondria it's being shuttled into something else and I I mean this is fundamentally the the cause of insulin resistance because when the body senses that the mitochondria can't do that conversion process the cell basically says because I can't convert this I don't have the capacity to convert it to usable energy I'm going to take the substrates and I need to block them I mean got to turn them to basically a storage form which inside the cell could be toxic fats like ceramides and diog glycerol and I'm also going to block the cell from taking any more substrates because can't do anything with them that is fundamentally a root of insulin resistance so the body says okay we're going to block the ability of the insulin receptor to transduce its intercellular signaling pathway we're going to block it and when that insulin binds we're not actually going to allow for glucose to come in so essentially insulin resistance is the cell compensating for the mitochondria being broken and telling the insulin receptor that it it you know that it's not going to be functional and so you don't get the glute for you don't get the glute receptors on the cell membrane to allow the glucose to come in so that's that's insulin resistance again we talk about that as the problem but the problem is actually inside the cell leading to that you know so that's why just giving someone insulin isn't necessarily answer we have to increase mitochondrial capacity to let the flow happen through it to energy which then trickles up into relieving a lot of these problems so to answer your question what we really want to do to increase our metabolic capacity from a first principal perspective it's we need to make more mitochondria we need to get each mitochondria to be more functional and we need to have each more functional mitochondria processing more energy substrates it's it's really that simple and the beauty is we can do all of those things if you actually break down like what it what those three things mean it means promoting mitophagy the recycling of o old mitochondria to to new mitochondria it means promoting mitochondrial biogenesis it means increasing the oxitive capacity of our individual mitochondria it means improving mitochondrial Fusion which is actually when mitochondria come together to form long chains of mitochondria that are more efficient so there's like a lot of technicality to like what it means to print more mitochondria have them each be more efficient and have each one do more work but that's really what we want to do and that's when it just kind of gets into the simple Habits Like There's simple things we can do for each of those things for mitophagy you know we can focus on various types of like endurance exercise and uh high-intensity interval exercise there's compounds like Ethan a that promote mitophagy um when we talk about improving our you know oxy of capacity this is things like the Sprint workouts we want to build more mitochondria this is resistance training literally telling the body to make more so but first principles it's how do we get more of these working better do doing more work every day and then we think about you know you look at the data on walking and it's like people who walk more than 7,000 steps a day have a 50 to 65% lower chance of dying in 10year follow-ups and it's like yeah because walking is literally a glucose disposal signal so you're just simply asking it's not a great biogenesis signal it's not a great mitophagy signal but it's a great disposal so if you're doing lifestyle habits that do one of those three things which we can of course go into more you're improving the cell's capacity to um do that conversion process better I'd like to take a brief break and acknowledge our sponsor ag1 by now most of you have heard me tell my story about how I've been taking ag1 once or twice a day every day since 2012 and indeed that's true I started taking ag1 and I still take ag1 once or twice a day because it gives me vitamins and minerals that I might not be getting enough of from Whole Foods that I eat as well as adaptogens and micronutrients those adaptogens and micronutrients really critical because even though I strive to eat most of my foods from unprocessed or minimally processed Whole Foods it's often hard to do so especially when I'm traveling and especially when I'm busy so by 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drink a1.com huberman there's a lot of great science and a lot of um great stuff related to testing and assessment of one's metabolic Health that we should get into and will get into but since we touched on lifestyle and because we've been talking about the sort of dysfunctional dark side for a bit maybe we could just touch on some of the lifestyle factors that you just mentioned because I do think it's important that people really start to feel into their sense of agency and here we're talking about um things that are relatively low time investment certainly don't have much Financial cost in the sense that they could be done in gyms and with fancy equipment but they don't require that um again I I want to point out that these are not like strict prescriptives but if you had a magic wand and because you are interested in the health of humans um let's talk about a few of these things that can improve um glucose disposal um and mitochondrial function uh mitophagy the removal of of dead or dysfunctional mitochondria so they can be replaced um let's talk about the walking one first you said 7,000 steps a day I don't track my steps um what are we really talking about there we talking about taking the stairs and trying to walk as much as possible maybe we like if we were going to just give like a really crude prescription you're a doctor so you can prescribe things um what would you tell people to do like how many short walks per day is is it like three is it five is um what are we talking would say up I mean at at least three I would say aiming for more than that is good though there's so so to sort of just give a sense of the picture of walking if walking were a pill it would be the most uh impactful pill we've ever had in all of modern medicine um there was a paper in jamama uh 6,300 participants followed for uh 10 to 11 years and the people who simply walked seven th000 steps per day compared to less than that had in up to 70% lower risk of all cause mortality in the follow-up period so not causality but it's it's pretty incredible they've done follow-up research with slightly different numbers showing again though like many thousands of people uh in the study followed for about 10 years 8,000 to 12,000 steps per day was associated with 50 to 65% lower uh all cause mortality and this has been played out in many many studies showing about a 50% reduction in Alzheimer's uh dementia obesity type 2 diabetes depression cancer gastric reflux just all across the board and I think the key thing is that it's not about the steps it's about the fact that muscle contraction is medicine when we contract our muscles even in a very like lowgrade way like walking or doing a couple air squats you know we're activating ampk and we are essentially causing that cell to have a stimulus to push glucose channels to the cell membrane most of the time the glucose channels are like in vesicles ins in little bags inside the cells they're not on the cell membrane so of course that's going to keep the the glucose in your in your bloodstream not being processed by the mitochondria so when we think about steps it's a proxy metric for just moving more throughout the day so let's take two people you have a person who's walking for 1 to two minutes every 30 minutes throughout the day maybe they're exercising at the end of the day or the beginning of the day maybe they're not that person is stimulating glucose channels to be at the membrane all day now let's take another person who works out really hard for one hour in the beginning or the end of the day they feel great about it they've checked that off their box but they're sitting the entire rest of the day yes they have gotten the benefits from the exercise but for a lot of that day those glucose channels are inside the cell not doing the work they could be doing so I think about these little teeny short walking breaks or push-up breaks or air squat breaks every 30 minutes or so throughout the day as me essentially inside the cell pushing the glucose channels the cell membrane to make them constituently active um it's totally different physiology and it's so easy so it's not about the steps it's about muscle contraction regularly throughout the day and and this has been shown out in actually more clinical research which has taken there's been several studies two that I think are fascinating where they basically took two groups and they said okay we're going to have you walk 20 minutes before each meal three times a day 20 minutes after each meal so that's also three times a day or for like 2 minutes every 30 minutes throughout the day so these are three separate groups either 20 minutes before I either 20 minutes after or 2 to 3 minutes every 30 minutes all added up to 60 minutes of walking or light jogging a day I'm kind of paraphrasing two different studies that showed the same thing one was jogging one was walking but it was basically chunks versus short walks every 30 minutes throughout the waking day the groups that do the short movement regularly throughout the day even though the total time is the same across all the groups have significantly lower 24-hour glucose level averages 24-hour insulin level averages they are metabolically healthier and I believe and the research mechanistically has shown that it's because we're constitutively putting this these channels at the membrane to take up the substrate use the substrate so this is not in uh to to replace exercise but I think it's a reframe I think the concept of exercise is something we're really very wedded to in our Western culture and you look at more like the blue zones and the centenarians and it's like they're kind of moving is built into their everyday life so we've taken movement out of our everyday life as these knowledge workers as we've been industrialized and then we think that exercise replaces that all day movement but biochemically it does not so I think a big part of kind of digging ourselves out of this chronic disease mess and creating capacity for mitochondria is finding ways to take a lot of the activities we do now seated and just find a way to do more of them moving standing or walking or if that's tough you really need to sit at your desk all day then every 30 minutes taking 2 minutes to do some just light movement Flex those muscles get the glucose channels at the membrane get the mitochondria active so and I think another fascinating stat is like our gym memberships in the US have doubled since the year 2000 and obesity has gone up in the same period so there's some mismatch between our obsession with exercise and our actual outcomes that we're seeing and I think it's that we have not actually rebuilt constitutive movement into our daily lives very interesting because I think a lot of people are now working out so to speak doing resistance training which I think is terrific ter used to be such you know such so restricted to Niche subculture stuff like bodybuilding preseason football military Etc and now it's a more ubiquitous uh for everybody men women young old that's terrific same thing with things like yoga and cardiovascular training I mean I it like to study the history of exercise culture and it wasn't but in the' 60s when you know jogging was considered kind of like whoa that's like a really esoteric Niche culture thing so A lot's changed um I love the prescriptives you gave because it's just very straightforward a couple of short walks um it just makes so much sense um and I love the visual and I hope people will really hold it in mind so I'll reiterate it the the um translocation of these um energy utilization stores vles as you call them these little packets from the center of the cell out to the cell surface where then they can be Evol involved excuse me in metabolic processes and the utilization of energy in ways that um otherwise they wouldn't and glucose disposal being a big part of this so I have heard that a short walk after a meal will reduce blood glucose in a way that's really dramatic huge amount 30 35% just taking a walk around the block after meal that's definitely a prescription I think everyone should do because the research is so strong on it is that building in simply a 10minute walk around the block or a dance party in the kitchen moving your muscles for 10 minutes after a meal can drastically reduce your glucose response because you're just bringing all those channels to the membrane you're taking up the glucose you're using it it's a whole different physiology than sitting on the couch after a meal that's very high impact it's high leverage if it's after a meal so highly recommend that and the levels data and clinical data has shown that out time and time again whenever I go to a city like New York when I am forced to walk more I I always just feel so much better we also know that the optic flow that one experiences with walking has some interesting effects on the lyic pathways and quieting of some of the anxiety and stress related Pathways um this links up with things like EMDR although there are factors that are separate from EMDR basically moving through space um not outer space but walking through space with optic flow has a certain um anxiety reduction function in the brain which they beautiful data there in my opinion um okay so that touches on walking you did mention higher intensity exercise so let's um keep it within the cardiovascular realm for now so um getting heart rate way way up you know getting breathing hard for you know some minutes um each week maybe a couple times per week um seems that's a good way to increase mitochondrial function and mitochondrial number is that right yeah so you take sort of each each type of exercise we've got walking we've got resistance training we've got high-intensity interval training we've got endurance training and then we've got sort of more like zone two uh so we've got these different flavors of how we get our heart rate up how we get the blood flowing what we signal to the cells and each one actually has like a slightly different impact on the mitochondria when we think about biogenesis we're thinking mostly like endurance exercise and really um more of that zone two and like that is really going to be a stim inside the cell to print more mitochondria when we think about improving mitochondrial Fusion high-intensity interval training is really really good for that when we think about resistance training it's like that's like muscle hypertrophy we're going to be creating more muscle cells and we need more mitochondria for those so each one has kind of a different impact and I think this is where honestly I think the regular guidelines that we have even by our government you know actually make a lot of sense it's like work every major muscle group three times a week in a distance type training and then work to get 75 to 150 minutes of moderate activity so 75 minutes of strenuous activity or 150 minutes per week of moderate activity so that actually makes a lot of sense 80% of Americans are not meeting those very basic guidelines and 20% of Americans don't get any physical activity really at all activity for the average American is 3,000 to 4,000 steps per day which is less than 2 miles so we are not even close to even even meeting the basic recommendations that are out there but I think those are pretty reasonable resistance training two to three times a week most major muscle groups and working to you know get the get the heart rate up moderate level uh for 150 minutes a week or strenuous for 75 minutes a week those are going together to be potent stimuli for biogenesis mitophagy mitochondrial Fusion for increasing antioxidant enzymes that are going to protect the mitochondria from that oxa of stress um and the one that's just actually not in there in the in the sort of the basic recommendations for Americans is the walking and I would just absolutely add to that at least 7,000 steps per day based on what the the data is showing which honestly would probably take less than an hour total to do if you if you break it up throughout the day it's just a few minutes a day so that right there are going to be like a big multifaceted set of signals for increasing mitochondrial capacity in different ways terrific what what are your thoughts on um under the desk treadmilling I I don't own one of these but and I try and get walks and I definitely do my three resistance training exra uh sessions per week different muscle groups on different days so it ends up being each muscle group is hit directly once and indirectly a second time but I like to do a long hike once on the weekend a run in the middle of the week that's 30 maybe 35 minutes and then some V2 Max really short workout 12 minutes total where basically I'm just going for um you know the feeling that my uh heart is going to jump out of my chest and I'm going to get going to die from gasem of a but luckily thus far I haven't died nonetheless um the total time commitment isn't that great but I find that I'm at a desk a lot and I have a standing desk is it wise to get a treadmill to treadmill under the desk seems like it would be one of the best things one could do I'm a massive fan of under treadmill desks because genuinely I believe that if we if we move more of our daily activities that we're doing seated indoors to Outdoors moving it would it would it would radically change the health of the United States with real physiology underneath it so there's actually been research on underdesk standing desk that is pretty interesting small studies but they you know took a handful of people I think it was around 10 um in a workplace environment and they had them use under desk treadmills for two and a half hours uh per day during the workday so not a lot at very so speeds for uh two weeks and people lost on average 2.6 lb of fat and put on 2.2 lbs of lean mass wild in a very short period of time the study makes a somewhat wild claim that if this were extrapolated to a year we anticipate that we could see a loss of 44 to 66 pounds assuming assuming it's line near progression exactly which is not which is not the case folks but I that's why I'm saying it was it was a pretty but that was there in the discussion and but I think that short period is quite interesting um so that's that's pretty significant and that's just for two and a half hours a day so I think now that they're about $150 on Amazon these underd dust treadmills I think for anyone who's a knowledge worker it's a good thing to have at your house and the way I use it is like I basically just force myself to start my day on the treadmill desk and I say to myself if I don't like it after 5 minutes I'll sit down if I need to sit but I'll start and just see how it feels and then an hour goes by and I've forgotten I'm even on it is that right so you're able to work without thinking about having to to um to treadmill I am putting it at such a slow speed I think I'm usually walking at like one mile per hour I mean it's very very glacially slow I do put my aura ring on my second toe when I do this because otherwise it doesn't count my steps because if your hands are your desk they uh they it won't count your steps because the AA Rings measuring hand accelerometry yeah but um it it it's incredible how even at a 1.0 one mile per hour speed after two to three hours you're easily going to get six seven 8,000 steps and then throw in a couple other short walks throughout the day and you're you're getting there easily so it's just a it's just a great way to build back in what modernity took away and that unfortunately is unavoidable that that regular movement for good physiology so I'm a big fan of them and the data suggests that for a couple hours a day they can actually have a have an impact on body composition which I think is is a great easy inexpensive thing for people to do but if you if you don't want to buy one like just set those timers and uh and build in the walks you know throughout the day outside terrific yeah I'm a I'm a fan of getting walks when I can I also I wonder your thoughts on there was a study not sure if you're familiar with it um published at the University of Houston where they looked at what they called Solus push-ups um which all the gym goers are going to roll their eyes um imagine sitting down and raise pressing your toe against the ground and raising your heel so kind of like seated calf raay but no weight right under the desk and this study had some remarkable claims and conclusions um which included as I recall that the activation of this muscle the Solus which makes up about 1% of the body's total musculature um involved caused rather a disproportionate use of blood glucose so it mobilized blood glucose in a good way um and the idea was if people would it's not just bouncing your knee but would actively push their toes against the ground and raise their heels as they were seated and doing work that somehow there would be a positive effect on metabolism and blood glucose utilization I talked a little bit about this on social media and a few other podcasts and and it was interesting to see that sort of attacks that I got like people really didn't like the idea um that this was any different than so-called neat non-exercise and um activated thermogenesis so it's known that people that fidget a lot or or move around a lot burn a lot of calories this actually goes back to some really beautiful work um several decades or more ago from Rothwell and stock who talked about like the fact that animals and people who fidget a lot burn a lot of energy they tend to be thinner they tend to have lower adapost tissue stores um and it's because they're just burning a lot more calories and this is actually what um people who suffer from anorexia which is by the way the most deadly of the psychiatric condition so it's um we're talking about true anorexia are encouraged not to do because um they either do it spontaneously or they learn that it's a very efficient way to burn calories and that's not what they need but many people do need to burn more calories so um bounce in the knee that thing that drives everybody crazy if you're not the one doing it um Solus push-ups uh what are your thoughts about this in that study we don't have to pick it apart in detail but I thought it was kind of interesting it's all coming back to just moving the body as much as possible during the day Contracting muscles Contracting mus Contracting muscles it's medicine and I I find the concept of neat just endlessly fascinating you know because we we kind of come up with this term non-exercise activity thermogenesis and the data is really good about it like it's basically shows that this is a a prime potential intervention for the Obesity epidemic and it all goes back to the cell like it's a it's essentially a stimulus that's telling the body to stay metabolically active as opposed to keeping all those metabolic pathways you know dormant during the day um and I think that it just it is funny though that like we have these acronyms for basically like this is just the way life was a hundred years ago if you look at like the 1800s Almost 100% of Americans lived on a farm basically like pre-industrialization pre- urbanization most Americans not 100% but close lived they grew some of their own food they lived either on a farm or had a large garden now that number is less than 1% so like movement was just buil into everything we did and and you think from there like what has happened like we were outside we were moving our activities of daily living involved movement and if you just take the grocery example then it moved to like okay maybe farmers markets and sort of like you know outdoor open air markets then it's supermarkets then it's you know now it's literally buying food online with the click of the button and now some people aren't even doing that they're literally on the food delivered to them with Uber Eats so at every level we've taken away movement from everyday life and now we have sort of an acronym to like bring it back in but really it's about just you know giving the body stimulus stimuli that the cells have been entrained to expect throughout all of human history and building the back into our Modern Life so I think neat it's incredibly important and I think it also brings up this point that like is so critical which is like I really think our way out of this chronic disease epidemic and even for people who are listening don't have a chronic disease any real chronic symptoms we're dealing with and just the fact that we're not feeling as good as we could like the way out is pretty simple like it's it's some of these basic things like walking more throughout the day moving more throughout the day getting outside you know eating clean unpoisoned food the the a lot of these things that have the best data are so simple and I think it's like really important to just always remember like the game and the industry it's all about how complex can we make it like specialization talking about some of the minutia but like at the end of the day all the simple habits that we know are healthy like fundamentally improve cellular biology and like some of these things like the neat like the walking like it's emblematic of the fact that um some of the simplest Solutions are the ones that are by far the most effective and I think I think the biggest misconception in healthcare right now is that the way out and the way to get really back to to True incredible health is complicated like it's it's really not that complicated we we've got to move more you know throughout the day that's one of them and you know on each pillar that we touched on earlier food sleep all of this you know when we talk about the simple habits that know work the reason they work is because they all positively impact the mitochondria they positively impact oxy of stress they positively impact inflammation so yeah I love it I love Simple Solutions that hit multiple cellular Pathways that can make everybody healthier I'd like to just take a quick break and acknowledge one of our sponsors insid tracker inside tracker is a personalized nutrition platform that analyzes data from your blood and DNA to help you better understand your body and help you reach your health goals now I've long been a believer in getting regular blood work done for the simple reason that many of the factors that impact our immediate and long-term Health can only be addressed that is can only be measured with a quality blood test now one issue with many blood tests out there is that you get information back about lipid levels hormone levels metabolic factors Etc but you don't know what to do with that information with inside tracker they make it very easy to understand your levels and what they mean and specific actionable items that you can undertake in in order to bring those levels into the ranges that are optimal for you insid tracker also offers insid Tracker Pro which enables coaches and health professionals to provide premium and personalized Services by leveraging inside trackers analysis and recommendations with their clients if you'd like to try insid tracker you can go to insid tracker.com huberman and you'll get 20% off any of insid tracker's plans again that's insid tracker.com huberman I'd like to talk about assessment blood tests in particular um I remember in college I was just very curious about blood testing and I had read a little bit about it but it was really hard to access um I actually went to the Student Health Center and said you know can I just get um like my lipids measured some hormone stuff measured I was in great health I just want to do that and they're like no like what's the issue you know why why why would you do that now it's very easy to find places that will do blood tests but there is some cost often um and nowadays thanks to your efforts your innovative and Engineering efforts and the efforts of others there are ways to measure what's in your blood blood glucose in particular um with continuous monitoring and with um snapshot monitoring so um let's talk about blood tests what what do you think are um the three to five things that basically everybody if they can should know about what circulating in their blood I'm I'm imagining LDL HDL this kind of thing I guess apob is a big uh favorite of our our friend Peter AA um fasting blood glucose continuous blood glucose postmeal Etc just kind of evaluating how exercise food Etc impacts blood glucose and then I'll leave the other categories open because my my point here is not to answer the question for that's what comes to mind you've got you know you've got the big ones so this this is key is that every single person listening I hope after this episode will go to their health record or send their doctor a message and at least get the following test and the first seven that I'll mention are very basic and people might take umage to them because obviously there's a lot of debate about like what's everyone's favorite lab test but I think about it as like what are the basics that everyone should know and then what's like the next tier up that are easy to access and are cheap that'll give you a lot more richness but which you still might have to kind of fight your doctor for so the first few that you will not have to fight your doctor for and are often free on an annual physical and literally Define metabolic syndrome are fasting glucose fasting triglycerides HDL cholesterol hemoglobin A1c total cholesterol waste circumference and blood pressure okay sorry I hate to interrupt and my audience hates it even more but I'm going to just could you just explain what each of those is and what it what it corresponds to yes great thank you and and I will say first of all the reason I'm choosing these it's not it's not even my own choice really it's it's two reasons one is that the two studies over the past 5 years that have shown Us in large populations that the vast majority of American adults are metabolically dysfunctional use those biomarkers so I think because of that it's important to know them and the two studies that I'm referring to are one from UNCC in 2018 which showed that based on those biomarkers 88% of American adults are have suboptimal metabolism and then a follow-up study from the Journal of the American College of Cardiology from last year show that that number has gone to 93.2% of American adults are suboptimal in their metabolism and these are the metrics that they used and they're very basic if you had to pay out of pocket they would be less than $100 so let's talk through them why they're great is because together they give you kind of like a tapestry of what's actually happening inside the cell if you choose to look at them that way if you read The Tea Leaves of them are the doctors often if they see all these lab tests it'll be an electronic health record we've all been through this experiment experience they'll come up on the screen and there will either be like a green orange or red color next to it like it's high it's low it's borderline and the doctor will basically it's very algorithmic oh you know your LDL is high we need to bring it down oh your glucose is high we need to bring it down oh your blood pressure is high we need to bring it down but what I'm inviting people to do is understand a little bit about each test and then read the Tea Leaves of what it's telling us about our mitochondria so let's start with fasting glucose so f fting glucose when you look at these studies that I'm referring to they call Optimal less than 100 so to define whether you were in that 88 or 93% you had to essentially be in the their their optimal range for all biomarkers not on medication so I'll quickly run through what their ranges were my ranges for optimal are tighter than these but fasting glucose less than 100 triglycerides less than 150 HDL above 40 for men or 50 for women hemog glob1 C less than 5.7% total cholesterol to HDL ratio less than 3.5 to 1 waist circumference less than 35 in for women or 40 in for men and blood pressure less than 120 over 80 if those things were in those ranges and you weren't on medication for blood sugar or or blood pressure or whatnot you were considered optimally metabolically healthy that's now 6.8% of Americans um all of these biomarkers are easy to change in one to two months I would say with simple lifestyle habits could you remind us what hemoglobin A1c is I think most people are familiar with HDL cholesterol being the quote unquote good cholesterol and LDL being the bad cholesterol and as I say that I know I'm going to get dog piled oh totally but I'm not sure that I adhere to that I'm not sure I don't adhere to that I'm not sure about a lot of things but I am sure that most people think of them that way um so just as a yeah to stay functional here we we'll frame it that way for now with with the caveat that that might not be the whole story isn't the whole story but um triglycerides fat in the blood fatty stuff but so key to understand about the triglycerides it's not PE we don't want to confuse triglycerides with eating more fat triglycerides are a storage form of excess carbohydrates in the blood so this is why it can tell us something about and I know you and you and Rob lusting talked about this at length but LAN yeah I mean one of the things that's really tricky gosh is that the the language around nutrition and health is complicated because people hear the word fat they think body fat but then they also think the macronutrient fat we just need more words to better parse totally the reality in biology we call the two major groups of of people lumpers and Splitters lumpers like to lump everything together it oversimplifies and complicates Splitters like to split everything give a name for everything individual name for everything it complicates and so there's a middle ground right there's a there's a land of reasonable people and nomenclature and unfortunately that does not exist on the internet nor does it exist in any one specific subfield of medicine or science I mean so much of the confusion out in the world is because of a lack of adequate language right in order to explain okay so um the triglycerides are a reflection of excess carbohydrate intake and how it's helping us with that tapestry of understanding the trifecta of bad energy is that if you think about it let's just go back to that cell and that Poe mitochondria that's being absolutely decimated by our environment uh and its capacity is low okay so that mitochondria is like I can't process glucose or fatty acids to ATP very well so I'm going to block their entry into the cell so now you've got glucose rising in the bloodstream so okay fasting glucose that was one of our enviral markers if that's going up that is a little bit of that tapestry of maybe something's going on inside the cell that's blocking the entry into the cell so it's rising the bloodstream okay well where's all that the this the body does not want lots of glucose floating around in the bloodstream because it can literally independently cause endothelial dysfunction which is basically blood vessel problems it can cause oxidative stress in the bloodstream it can cause glycation which is sugar literally just sticking to things we the body doesn't want that glucose high in the bloodstream so it converts it to triglycerides to be stored in a storage form of energy that's a key point that I think is helpful to understand is that the body it's always trying to like kind of keep things in the right range so it'll convert things so then triglycerides a picture in your blood of glucose being high and triglycerides being high is very much should signal to everyone when they look at their Labs that there's probably something going on inside in inside the cell that's blocking the cell from being able to use and process it's a sign of mitochondrial dysfunction and chronic overnutrition too much substrate not enough processing glucose is going to go up Tri are going to go up and so so then if you kind of squint and read the tea leaves it's like huh I think metabolic dysfunction and what's fascinating is that the travesty in our healthare system is that a patient might go into the doctor and their fasting glucose is 99 one point under what we'd consider the normal range and their triglycerides are 149 one point under what we'd consider the normal range from these things that doctor might say to that patient you're totally fine both glucose and triglycerides are normal but that's just really problematic because they're on the upper end of normal for both of those and so really what that would say to me as someone thinking about the mitochondria is like this person is definitely metabolically dysfunctional they're on the highest end of normal for both triglycerides and glucose there's something there's definitely insulin resistance going on here I would much rather see that glucose at 703 and that triglyceride at 50 which to me would say oh this cell's processing through energy great and things are moving through and we're not backing up in the bloodstream we're not converting to triglycerides so that's where really optimal ranges get in but but so that's so that's glucose and triglycerides why if those are starting to creep up it's a sign that something is happening metabolically and then when we look at some of the other biomarkers so hemoglobin A1c is really so that's a marker that's looking at how many of the hemoglobin molecules that are in the red blood cells that carry oxygen how many of those hemoglobin molecules have sugar stuck to them and that's glycation so you're looking at glycated hemoglobin and you can imagine that if the concentration of glucose is higher over time more glucose is going to stick to red blood cells and that's going to create a higher percentage of glycated hemoglobin so that's why that lab is represented as a percentage so less than 5.7 is what we want you want those cells nice and smooth and slippery smooth no sugar stuck to them causing dysfunction um and because blood cells last for about 9 to 120 days hemoglobin A1c is giving us a basically a snapshot of average blood sugar levels over 9 to 120 days and if that average is higher again probably a sign that cells are rejecting glucose from the cell and it's causing to rise in the bloodstream and then just talking about one other biomarker in that that we talked about which was blood pressure people might say well how does blood pressure relate to like what's going on inside the cell you know in the mitochondria and whatnot and a really the fascinating link is that when that cell becomes insulin resistance which again is a compensatory mechanism for mitochondrial dysfunction the insulin is going to rise in the blood because the body's insulin resistant so the body's going to turn out more insulin to try and overcome the insulin block to drive the sugar into the cells so insulin levels rise well insulin is one of the key activators of nitric oxide which is the molecule in the blood that dilates and relaxes blood vessels and so when we become insulin resistant and we're not responding to that insulin signal we end up getting less nitric oxide activity so this is how kind of looking at even these very basic very cheap biomarkers through the lens of basic cellular physiology we can start to see man my body might be like underpowered I might I might have a mitochondrial issue here so that's a few of those tests that we really want to shoot for terrific and um thanks for bringing up blood pressure again it's sort of um comes across to many people as old school right but when AO was here um one of the several times he was here he he really pushed on blood pressure is such such a key metric right I mean obviously if blood pressure is high you're getting less nitric oxide through for whatever means here uh vessels and capillaries are constricted um cells aren't able to use the energy that's coming in there's excess energy there's buildup of metabolic waste there's all this stuff and now we can start to see the picture yeah it's trying to emerge and as you mentioned um briefly these markers can be put into healthy range or maybe even fantastic range in a very short period of time so we'll talk about um how to go about that um in terms of getting a basic blood test is you're a physician what's the secret code um I'll give away one that um a former guest who's also an MD shared which is oftentimes if you ask your physician for a blood test they will say well unless there's a particular need or you're um struggling with something they won't give it to you but if you have a shift from Baseline in a symptom or in a number that can help all the Physicians are going to come after me now with I guess with stethoscopes um uh I'm willing to Stand My Ground um if you want a blood test it's often useful to mention that there's 's been some Market shift um you want to be honest right but some Market shift in sleep in lifestyle in how you feel standing up sitting down I'm not trying to you know lace people's minds with ideas to to uh create narratives here but um oftentimes where Physicians are resistant they'll be more amendable if they understand that hey like something's changing and the patient saying something's changing it actually would be irresponsible of them to not give the blood test so there you go um Bring It On MDS so yeah truly and I think the nice thing about the again very basic tests and there are so many other tests that I talked about in my book and that you've talked about on your podcast apob uric acid fasting insulin hom IR hscrp liver function test ggt all these other tests that are great that can really tell us more about mitochondrial dysfunction oxidative stress chronic inflammation but the ones I'm mentioning are the ones that you will not have to fight with your doctor about like the the the everything I just mentioned like the doctor should order on an annual physical and it's really about us learning to act like read the Tea Leaves of what they're saying and not look at them in this algorithmic way but like how together if they're creeping up or if many of them are a little bit high like we need to focus all of our energy on improving mitochondrial capacity basically and and bring those numbers down which we can do very very quickly once you start getting the mitochondria moving through more of those substrates a lot of them will just naturally come down now in the book I give scripts to literally talk to your doctor with because you are going to get push back often if you ask for a fasting insulin I would say probably I mean even though doctors are waking up a little bit like maybe 85% of people are going to have their doctors say they won't order that for them so I actually think there's a huge benefit I hate to say it but like going outside the system this is where I think innovation has been valuable there's a lot of like amazing companies doing direct to Consumer lab testing so you can basically avoid the hassle and some of them are very affordable there's um function health is a company that's doing 110 biomarkers including all the key metabolic biomarkers for less than $500 and they'll do it twice a year so you don't ever have to and then they do interpretations um insid tracker uh next Health levels is doing labs and so there's a lot of this springing up because I think people are sick of fighting with their doctors to get a a crumb of information about their health and it's it's it's we should probably be testing these I would say three to four times a year um and the beauty is is that like I think a lot of what keeps people down in the health world is that they're confused about what to do there's a lot of noise there's a lot of different strategies you know do I do you know paleo keto carnivore vegan Mediterranean do I do hit or Zone 2 or Ecentric it's like there's so much noise and the beauty with having a plan for understanding your biomarkers regularly is that you can cut through all the noise try a strategy see where you stand re retest in a few months and see if you're moving in the right direction s you don't have to trust your doctor you don't have to trust me you don't have to trust anyone you can literally trust your own labs and I I I say to people like if your labs are optimal and the ranges I just mentioned are not optimal like we you want to actually get to better than all of those if you want to be optim if your if your key metabolic biomarkers are optimal if you feel absolutely freaking incredible and you have no symptoms then you're probably doing the right strategy whatever that is vegan keto whatever like and and exercise and your lifestyle because that is showing that your cells are fundamentally working properly so I think that's just a really empowering message and now there's phenomenal companies that are cropping up to basically help allow people to do this on their own schedule which I think is really the future of health and actually will help lessen I think some of the intensity of the diet Wars you know because it's like people can just say like I trust my strategy I know I'm doing what's right for me cuz like look at all my biomarkers and I feel great you know so yeah what used to be the before and after um you know pre-diet exercise post- diet exercise um photos on social media are now starting to also include numbers which is kind of interesting I mean obviously these aren't randomized control trials but it's cool to see people posting their numbers yeah of things that are not just related to Aesthetics but are um or body weight but are related to health metrics yeah uh it's it's it's fun I think it it speaks to um a more scientific or at least a more quantitative approach to things and I think it's inspiring for people um thanks for putting those scripts in the book that people can refer to um let's say that um I go in for these blood tests I do the basic 7 and I find that my fasting glucose is a little high my triglycerides are a little high my LDL is a little high um maybe a few other things are okay so I'm kind of in the you know not in the Red Zone but I'm in the like I should probably pay attention to these things what are some of the things that one can do in order to try and move those needles in the right direction um I know we talked about walking in movement before what are a few others and maybe we could start to touch into Nutrition a little bit and then we'll pivot to um insulin and blood glucose I think on the highest level it's about running through what are the science-based things that we know in our environment can lead to metabolic dysfunction and take honest stock of how those factors are playing out in your life and then choose a few to start moving in a different direction so the ones that I think are ones that we can really control um and that are we know based on the science are impacting our mitochondrial and metabolic health is the food the Sleep the movement the emotional health the toxins our relationship with light and our relationship with temperature and your journey to Optimal metabolic Health might be totally different from mine because I might really need to focus on the food and the sleep and the emotional health and you might really need to focus on the toxins and the light and the movement and so it's a lot of it is actually taking stock on where the levers are in your own life where are you crushing it and where is there a lot of room for improvement so Step One is knowing like that those are the thing those are the things in our environment that we need to to basically improve to have to give our CS the best capacity and then of course checking your biomarkers to make sure your interventions are working but but food I think is one that is like totally unavoidable of those pillars those Seven Pillars food is one that most of us are getting wrong and that we really actually have to get right to improve our metabolic health for a lot of reasons I mean our bodies are basically 100% molecularly made from food that's so wild it's so wild every time I think about that I kind of like blows my mind like babies are 3D printed from food basically inside a woman's body it's it's wild to me and then what's so cool about the body what brings me just immense awe every day is that like we have this conception in our Western world that the body is like a thing that we're with throughout our life because we kind of look the same and we like age slowly so it's like Casey is a thing and Andrew is a thing but the body is actually a process the body and there's this amazing dos statement like life is a process not an entity I love that no I'm sorry to interrupt I'm just I I always you know wish that if people could understand that um with Biology and health understanding the nouns and the names is important but it's verbs it's verbs verbs verbs if you understand that things are processes or processes depending on who you are and where you live in the world um it all becomes so much more tractable yes and it's so much more hopeful because if I'm a process if you're a process then every every day we're eating we are changing the process whereas if you think you're a thing then there's no hope cuz I'm just I'm Casey and that's who I am and I have this disease you know and I think so much in our language actually of healthc care both are Western sort of despir nature like we don't really have a lot of curiosity with with process but even like the ideas the way we talk about disease I have diabetes you know and I I and and we don't even talk about diabetes cures which now a lot of people are curing their diabetes we call it remission like it's this thing that's a part of you and I think I just love this idea of like we're evolving every day and food is so important because again we take in 70 metric tons of food in the lifetime two to three pounds per day one metric ton per year on average and that is like the printer ink that's the 3D printer ink to create tomorrow's version of oursel which is molecularly different than the Casey of today that's a hopeful message because if we can give the body food which you know I think we again our our conception of food I think is very limited um food is the molecular building blocks of the body it is the cell signaling functional molecules that tell our cells what to do they act as transcription factors epigenetic modifiers um cell signaling pathway intermediates and it's also of course the substrate to change what the microbiome does and the composition of the M microbiome which is basically a pharmacy inside our bodies to create different molecules that can affect our health so food is certainly a calorie is a calorie from the concept of thermodynamics but from the concept of molecular information it has three massively important parts that are unavoidable for creating cellular health so I would just say that that is the pillar that we can drill be happy to drill into of like what do we really do to you know build build as much metabolic Health as possible yeah I want to focus now if you're willing on food not just macronutrients proteins fats and carbohydrates not just calories although that as well but things like timing things like fasting um and micronutrients which I think is a a highly underexplored topic so with respect to food um gosh I feel like we've all been exposed to pretty much every variation of you know it's it's all calories in calories out and by the way I believe in the laws of thermodynamics um so yes total caloric load matters total energy expenditure matters without question within the framework of not consuming excess calories there's a lot to explore however um I can just say for myself for what it's worth I'm not very hungry until 11:00 a.m. noon or 1 I'm okay not eating until then and just you know water electrolyt and caffeine does me just fine I can exercise Etc but once I start eating I I really enjoy eating and I mostly like the proteins I like Meat and Fish and eggs and I like cheese and vegetables and carbohydrates and fruit and all of it I like all the stuff and I I tend to like single or few ingredient Foods I just naturally do so I've been lucky in that way but I know a lot of people like sandwiches processed foods things that are combinations of ingredients what do we know about about kind of uh I don't want to say optimal but if one we're going to explore different ways of eating for sake of adjusting these biomarkers in the right direction and improving metabolic health is there kind of a a generic jumping off point would most people for instance be wise to um cut back on the total number of sugars or the the total amount of sugar rather and perhaps reduce the amount of carbohydrate and replace it with some lean quality protein I mean are there generalizations that we can make or is it really all just about not getting excessive calories and trying to get those calories from the most nutrient-rich sources well just Drilling in on two things you just said there so one thing you said that was interesting was that you're lucky that you like all of those foods and then the second thing was is it just about not getting excess calories but I think what's interesting about both of those is that I would argue that the reason you like those Foods is because you have given your body enough whole real foods that now everything in your biology neurobiologically your reward circuitry your microbiome your satiety hormone threshold all of these are now basically creating a situation in which you like those foods and then the caloric thing fits into that because the reason we're eating excess calories the reason chronic nutrition is happening and the reason we are quite literally in the United States eating ourselves to death for the first time in human history is because we're not eating real food and we're eating 60 to 75% of our calories of ultra processed nutrient depleted foods that fundamentally don't give our cells what they need and a real premise that I think is so important to realize is that our cells are brilliant and if the cells aren't getting what they actually need to function properly they will drive you to eat until they get their needs met unfortunately because the ultra processed food is designed to be highly addictive and it's devoid of what the cells actually need for good function we end up eating ourselves into a grave and now almost 80% of Americans are overweight or obese close to 50% of the country is obese we literally gloss over this as a culture it has become so normal in such a short amount of time but I always think about the fact that like there are really no other animal species in the world that have obesity and chronic disease epidemics and they don't have social media they don't have experts they don't have PubMed they don't have the FDA they don't have the USDA they don't have any of it and they have somehow figured out a way to stay at a healthy weight and to not get heart disease and it's because they're eating real food that meets the needs of their cells and so I think to just boil that down the root cause of the problem is that we have a toxic food supply that's no longer filled with the molecular information that our body needs to know to be satiated and to function properly and so through the complex biology of satiety hormones and neurobiology and microbiome function we are driven to eat so so so much more so truly the jumping off point for anyone on the quest to Better Health is to eat as much real unprocessed food from good soil as possible and of really of any dietary philosophy they want truly I I think if someone's eating real unprocessed food from good soil who is you know plant-based or who is keto they are going to have such a higher chance of meeting their body's actual fundamental needs and the good thing about biomarker testing is they can track for themselves if they are having good cellular function with that strategy there's been studies that have panned this out you know we we know that the mor Ultra process food you eat the higher risk of obviously obesity but also chronic diseases are but then of course there's an amazing study from Kevin Hall just recently where he basically locked people up at the NIH and he for two weeks he had them eat Ultra processed food and for two weeks he had them eat real food and people ate 7,000 more calories in the two week period uh when they were eating Ultra processed food versus the unprocessed food they were locked at the NIH I've been to NIH quite a bit um I don't it's it's great for a day job or a day visit I don't know that I want to be locked there that sounds like a that sounds like the Stanford Prison prisoner experiment I say this tongue and Chic and with such admiration for what he had to do but I think it's so amusing that you know we have this totally Franken food toxic food system that's that's largely Ultra processed and it took amazing Kevin Hall to basically do an NIH you know funded study where people what I say by locked is that they were impatience at the NIH and every had ad Li you know unlimited access to food during each of those two week interventions so it was two weeks of ultra processed food two weeks of unprocessed or minely processed food and they could eat whatever they wanted as much as they wanted in both groups and then they would weigh every single bite that was left on their trays so they knew exactly exactly how many calories they ate and literally just giving people this Ultra processed food which is devoid of what our bodies need and and therefore will drive people to eat more they ate uh 500 calories more per day for a total of 7,000 calories more in that two weeks and they gained about two pounds and then lost two pounds in the unprocessed Group which makes sense of course because a pound is about 3500 calories and so we have to do these kind of crazy studies just to prove what we kind of know is true which is that this Ultra processed food environment that's cropped up over the past 50 years is an experiment that has failed it has failed you know close to 45% of kids are overweight or obese now like it's not working and that really is uh the root cause so I think a lot of food is about quality and how do we actually really meet the needs of of the cells so that our satiety hormones get secreted and we naturally stop eating because just telling people eat less calories but eat whatever you want that's just doesn't work we have to inspire the body to not want to eat excess calories which we do by stimulating satiety hormones you know helping the microbiome support that process and then change our reward circuitry which is done with nutrient-rich the most nutrient-rich food we can possibly get and that's why I mentioned the soil because our food is drastically dep depleted of nutrients so when we look at that 70 metric tons of food we're eating in the lifetime it's just fasting you that's that's the information for our body what it's going to be built from how it's going to function well right now 60 to 75% is ultra processed so we slash the value because the ultr processing just like slashes the nutrients we slash the value of that 70 metric tons and then we have crappy soil because our industrial agriculture system which means the the food in some cases has 70% less of key micronutrients in it so that 70 metric tons what's actually useful for our body becomes so much smaller so what we want to do is basically expand and the value of that substrate we're putting in the body and that means real food unprocessed from good soil meet the needs of the cells naturally don't be hungry maintain a healthy weight um and you know something I talk about is that we could I mean we could talk about nutrition the biochemistry of nutrition all day but in my review of sort of the biology and the biochemistry like there's five main things I think we can strive for in our food that can really help meet the needs of our cells and and when it really comes there are obviously more things our body needs but if we strive for these five things we will ultimately I think eat a really healthy diet and that is fiber Omega-3s adequate healthy protein a good amount of probiotics and high antioxidant sources and if we build our diet around knowing a few things in each of those categories that we really love and stock our kitchen with it and make our meals a mixing and matching of each of those components and we get a good amount of those we will give the body a lot of what it needs to have mitochondrial Health reduce chronic inflammation reduce oxy of stress it's interesting for me to take a step back from nutrition as it's typically presented and think about the brain the hypothalamic circuitry that drives hunger and satiety and things like that and to map that on to what I've heard and I I believe to be true based on my view of the literature which is that we are largely meaning these circuits in the brain make us largely amino acid foraging machines because we need those amino acids in order to carry out metabolic processes and reconstruct any tissues that need repair and and Recovery not just from exercise but just daily turnover um removal of waste Etc um so we're foraging for amino acids unconsciously we're foraging for micronutrients and of course we need macronutrients we need enough energy from proteins fats and carbohydrates or some either combination of the three I feel like I'm sort of in the dying category of omnivores right I'm neither you know I'm not meat-based and I'm not uh plant-based I'm omnivores I think most people are omnivores actually but uh omnivores aren't discussed quite as quite as much as um the other categories at least not on social media but that you know we're we think of ourselves as getting hungry and wanting to eat um and I think eating the foods some of them I listed off before like Meat and Fish and eggs and vegetables and fruits and some I do like starches like you know rice oatmeal some pastas some sourdough Breads and things I love butter who doesn't love butter um of course none of that stuff in excess olive oil but if one looks at kind of that um Buffet of of options you realize you can get some high quality amino acids you can get some high quality lipids you um probably want to get more of them from olive oil than from butter but you can get the micronutrients you need provided those food sources are healthy now contrast that with a highly processed diet or even a minimally processed diet and you can get the taste you can get the macronutrients you can get the calories but you don't meaning the brain doesn't really have a sense of it can't directly map taste calories micronutrients on um onto one another and so you can imagine that the neural circuits and here I'm it's a little bit of hypothesizing SL conjecture but that the neural circuits responsible for hunger and satiety would get immensely confused by what's in a highly processed food right a Snickers bar if you like sweets tastes pretty good but it's unclear what's in it except sugar except some you know it's got a certain Snickers bar taste right but if the circuits of the brain are really trying to drive us to get amino acids and micronutrients um for bodily health and repair well then highly processed and even moderately processed food has just got be pure confusion I'm sorry to go long here but it reminds me of the of an idea I had once where like imagine if you took a pill that in greatly increased the level of dopamine norepinephrine acetylcholine and serotonin all at once that's polypharmacology and it might make you feel a certain way maybe good maybe bad and then afterwards you'd probably have a bit of a crash from as the drug wore off no doubt you would but let's say you wanted more of that feeling you wouldn't really know what to go look for because you don't know what what was in it because it's poly pharmacology so I feel like Pro highly processed food is polypharmacology whereas when you are eating foods that create a more pure experience of micronutrients amino acid content calories and taste those four things map to one another that intuitively we can start to understand oh I like this food and it's good for me and this is enough of it right I don't know anyone who of reasonable size that that eats like four ribeye steaks you know they eat one I me I'm sure there's some freaks out there that do that but you know one you know even small piece of quality meat is very satiating yeah you will self-regulate because the body like every other animal in the world is exquisitly designed to regulate hunger on a very intuitive level if we eat natural food it's you know it's I think it's almost ridiculous to talk about calories and isolation because the reason we're eating more calories is because we're eating ultra-processed food and so but I love what you just said Andrew about the brain and the poly faracy I think that literally is it's I've never heard that said and I think it's like processed food is like poly Pharmacy of food it is the definition of processed food which I know you talked about with Rob lusting the Nova four criteria is literally it's breaking down Foods into these constituent parts that were never meant to be separated from each other like the endosperm of a wheat kernel separate from the brand and the you know the germ um and then take that and like a little science experiment pair it up with all these other individual components and synthetic chemicals that are made in a factory and put them together to create this thing that the body I I I truly think our insatiable hunger again we're eating ourselves to death in the United States that's the reality our insatiable hunger and our chronic disease epidemic fundamentally is a lot of it's It's Mass cellular confusion and when you think about what chronic inflammation is chronic inflammation is biochemical fear on the cellular level well when you put this stuff into the body that's never seen before obviously that's going to generate some confusion and you know you could you could trace that back to what that really means with leaky gut and you know all the sorts of the real physiology of that but um there's a wonderful book that is called the end of Cravings by Mark shatzer he also wrote the Dorito effect but he talks a little bit what you're talking about which is ideal that processed food is actually the ultimate sort of food um based variable reward so in the way that it in like things that I mean I'm speaking the expert here but things that the body can't predict what the outcome is going to be are going to kind of get you in that dopamine motivation pathway and that's actually what processed food is doing is it's every time we eat a different ver we think we're eating a tortilla but it's like completely different than all the other weird tortilla Ultra process tortillas on the Shelf so every time we eat tortilla and our brain is this incredible prediction machine and as it's coming towards our mouth we're predicting what the load is going to be but we have no idea is it a Coke Zero is it a Diet Coke with Aspartame is it is it a regular Coke it all tastes the same but the nutrients that our gut are totally different so we end up actually triggering the motivation Pathways because of process food representing a variable reward whereas every time you eat a ribeye your body is pretty much getting a similar thing each time and so the prediction um matching is going to be more conducive to uh getting off the motivation treadmill for more which I think is so fascinating um but I think backing up a little bit one one concept I have for food that really helps me is really thinking about the body's always trying to help me be satiated and trying to help reduce my Cravings I literally just have to give the body what it needs I have to stimulate the body in a way that it will serve me in giving me satiety hormones to basically regulate my hunger and again with visuals I think it's so helpful I think about these cells lining our small intestine that literally have nutrient sensors like and literal receptors on the cell membrane in the luminal side of the gut that's facing all the food that are just sitting there like waiting to bind with these things in our food that will stimulate the cell to make the satiety hormone that poof effortly makes us not hungry gets rid of that grip of attachment to Cravings that all of us are so plagued by and like I think you know we have this intense conversation happening in society right now about gp1 analoges and OIC and mjara and all these things gp1 Agonist but like you know we rarely talk about the fact that like we have nutrient sensing cells of the gut the L cells of the gut that when stimulated appropriately will make glp1 and when stimulated the way they want to be will secrete hordes of glp1 for us and so how do we actually think about just literally giving the body what it needs to stimulate the society hormones and the processed foods aren't giving us those things you know the things that are goingon to um stimulate those cells well well the things that will I mean this is kind of fascinating if you don't mind going down a little road talking yeah please with the gp1 conversation I feel like so missing from the conversation is the idea that like from a first principles perspective there's three ways our body could make more gp1 we make more cells that make it l cells of the gut each of those cells makes more glp1 and importantly we can also inhibit the inactivator of gp1 which is an enzyme called dpp4 so gp1 actually gets rapidly degraded by dpp4 in the body so if we can figure out how to inhibit dpp4 we can raise our glp1 levels what is dpp4 it's an enzyme that breaks down gp1 said that and I missed I apologize so fascinating and so how often have you seen in the headlines oh here's some strategies to inhibit your dpp4 never because OIC is is you know on track to be the highest grossing Med in human history and just like we talked about in the beginning of the episode the whole industry this4 trillion doll health care industry is desperate for not us to not understand how to do the things that drugs could do for us so when we look at those three first principles approaches of how do we make more L cells get them to produce more glp1 from each L cell and then inhibit the breakdown through the inhibition of dpp4 for the first one we know that short chain fatty acids which of course are the byproduct of microbial fermentation of fiber in the diet stimulates the differentiation of more L cells in the gut so more short chain fatty acids more L cells can we translate that into support the gut microbiome eat more fiber eat more fiber and um we had Justin sonenberg from Stanford on a world expert in gut microbiome and he was a big proponent of based on work he's done um with Chris Gardner and others at Stanford so happens of ingesting one to three servings of low sugar fermented foods each day things like sauerkraut kimchi again low sugar variety is probably best yeah maybe not you said not kombucha yeah cuz that's going to be like the highest sugar of the fermented foods which people often go to but now sod cly the sauerkraut you can actually make your own sauerkraut Tim Ferris had a great recipe for this in the 4our chef you have to be careful because you know that you can create some unhealthy ferment you have to do it the way he describes so check out the the recipe it's online um or you can buy sauerkraut and the brins um drinking the brine off the sauerkraut or off um seems to be good for the gut that's such a great point which is that ultimately we want the short chain fatty acids which is the the the medicine that the the microbiome are making for us through the microbial fermentation process and we can basically do that in three ways one is we can eat more fiber which is prebiotics we can also eat more polyphenols because we're now learning that the microbiome actually processes they ferment polyphenols from our which is basically you'll find those in colorful fruits and vegetables um spices teas cocoa things like that so fermentation of polyphenols and fiber to short chain fatty acids which then we absorb um and then like you just said in a fermented food the bacteria in that food will be making short chain fatty acids by fermenting the food in there and then if we drink that we're getting the short chain fatty acids directly so that's the kimchi sauerkraut uh Greek yogurt kavass which I'm obsessed with which is like low sugar kambucha it's like made with fermenting beets basically good stuff it's such good stuff uh miso NATO so that's one that has been shown to differentiate more L cells in the gut we also know that people with 2 diabetes have much fewer L cells in the gut and it's hard to know what the causality is there but I think a safe assumption is like if we keep our blood sugar under better control and sort of stay out of that diabetic range it probably lends itself I don't know what the chicken in the egg is there but blood sugar stability more L cell differentiation and then actually ginsing has been shown to um to improve l l cell differentiation so that's just sort of one one set of things and I don't think the dose on sing has been has been settled but um very high antioxidant component plant when we look at actually stimulating more glp1 you've talked about your remate I think having like a a mild effect on glp1 but there's actually a lot of other things um in the literature protein of course Very potently stimulates these nutrient receptor cells and specifically like veiling and glutamine seem to have a potent stimulatory effect on glp1 so you're find that and like meat and turkey and eggs and things like that what are your thoughts on supplementing El glutamine it's controversial I know that some people do it um in an effort to relieve leaky gut but that's but there aren't any randomized control trials for that so the um depending on one's stance on what's required for uh uh kind of a threshold for for adopting something you know some people say that's crazy other people really swear by supplementing El glutamine maybe it's through this this route of increasing um L cells um that some of the gut relief might might exist I guess we'd have to explore it so that's speculative folks um so this is interesting these are ways to increase the cells that then make gp1 so fiber Prebiotic probiotic fiber and fermented antioxidants lowering blood sugar Jin saying so those are kind of the L cell ones the actual secretion of more glp1 the one of the most potent ones and the study that looks at this like the bar graphs are very clearly statistically sign significant lots of asteris is actually thids thids tell me more about thid thids are so fascinating thids are actually a structure in plants that are part of the chloroplasts so you know chloroplast and this also is fascinating because chloroplasts are basically the plant version of mitochondria essentially and thids are a molecule in the chloroplast and there's actually been research that shows that when you eat about 100 gram of spinach which gives you five grams of straight thy covid over 12 weeks daily it led to a a significant increase in glp1 and again I don't remember the exact it was two or threefold higher um secretion so this is in part so so so that's a direct stimulatory effect of the the L cells and so this is this equates to 3.5 ounces of spinach a day which is like nothing so just getting ra spinach or cooked spinach I think I actually I don't think it actually it might have said in the methods but I I would imagine raw because you want to get those undenatured thids in the gut so just kind of another actually thids do a lot of other interesting stuff they inhibit lipase in the gut and so actually help more fat get down to the distal small bowel and promote satiety so this is one of the reasons why you talk about oh the people who eat all these healthy foods and greens they're less hungry it's like it's biochemistry like there's stuff happening in there that is making the hunger signals go down through things like inhibiting lipase you know in improving gp1 secretion so other things for gp1 secretion the thids also Fiers has been shown specific amino acids so high protein foods things that involve a lot of veine and glutamine uh green tea and specifically the uh elic the EC um ecgc that uh is one of the compounds in green tea that's been shown to stimulate glp1 curcumin um so there's several things that are all in that like food you know basically things you would associate with a healthy diet but we actually know they stimulate glp1 so I you know those are all things I try to include in my diet and the last one is inhibition of dpp4 and that one there's just actually when you look at the research there's some kind of random foods that tend to inhibit dpp4 um black beans Mexican oregano other forms of oregano Rosemary guava and um I wrote this one down because it's a word I hadn't seen very much before I started digging into this but mtin which is found in berries cranberries and peppers and and Swiss chards so all that is to say ultimately many of us are gripped by cravings and the idea of have you know just sort of not being constantly driven to eat more which I would argue that about 80% of Americans are feels really hard to overcome but a lot of it is literally just communicating to your CS in in a clear way through food to help you be satiated and the science can show us how to do this and a lot of it comes down to eating essentially what you were talking about how you eat omnivorous protein um healthy sources with nutrient you know density and lots of colorful fruits vegetables um spices herbs things like that um so yeah yeah it's interesting um again these aren't randomized control trials nor are they peer-reviewed studies but I have a few friends who I've known for most of my life who really struggled with their weight uh carried a lot of excess weight and we starting to suffer health issues um in their even their 30s but in their 40s I'm 48 so they're my peers and so they're about that age range and they've all done extremely well meaning they lost a tremendous amount of body fat are terrifically healthy now by way of basically restricting their uh food intake to proteins so fish and meat eggs fruits and vegetables they basically just cut out starches and um but I don't think it was the starches per se I think it was the satiety that comes from eating high quality protein fruits and vegetables and from limiting the number of Highly processed foods and actually the toughest thing for all of them was to um stop asking me or themselves rather like can I include this condiment this this you know and what's interesting is all of them now seem to really enjoy eating Foods in their more pure form and I'm not somebody that like pushes on this on my friends they just come to me and say like how do I lose 50 lbs with um without having to exercise it all off you know um as the only source of of of weight loss they they all exercise as well but um it's just so daunting to try and lose you know 20 30 40 lounds and to do so quickly and then to keep it off cuz they've all had the experience of going on a diet and then you exercising a lot then um the point here is that I really think there's something powerful about that relationship between taste macronutrient value micronutrient value and um satiety yes I think there's really those powerful associations because the brain is such an associative machine uh one thing that I should have um said before um and I know most people are familiar with OIC yeah um and its commercial names are I forget what the the um OIC is the commercial name and munaro and movi and yeah got it um is that glp1 acts more or less as an appetite suppressant um powerful appetite suppressant so um many millions of people are now taking uh gp1 analogs is that right I think there were over 20 million pres scripts in the United States wow last year is it expensive it's it's $20,000 per year does insurance cover it typically uh right now insurance is covering it for indications um but there is a allout assault uh from the pharmaceutical industry to essentially classify obesity as a genetic disease and a chronic disease in order to be able to feed this medication more into the insurance pathway and essentially get more taxpayer dollars to pay for this medication um and it is extremely expensive and it's on track to be the highest grossy medication in history because uh it's now being recommended for people with obesity type 2 diabetes and then the American Academy Pediatrics recently has talked about giving this to children as young as 12 as part of the first line for overweight um and you know I think really it's such a travesty based on the conversation we've had because what OIC does not do in any way shape or form is impact the toxic environment that we're living in that's hurting our mitochondria losing weight is different than improving mitochondrial function and mitochondrial dysfunction is the root cause of basically every chronic illness and symptom that's torturing American lives today and so in many ways it represents like the ultimate Band-Aid for an environment that is not changing um and when you think about what we could do with $220,000 per year and it's a weekly injection so say well per person like oh it's and it's a medication that is intended to be taken for life because when people come off this medication many people are gaining back all of the weight or even more weight afterwards and then there's been conversations Peter Tia is waiting on this about loss in lean mass you know part of the weight loss is disproportionately muscle and so there's a lot of concerns about it um above and beyond its ability to lower the number on the scale that uh we should all be very alert too because um you know the reality is is that the 40 trillion cells in our body are in an environment in the western world right now that is not conducive to core biologic functioning and there is obviously no shot that can mitigate the multi-front assault on our biology that ultimately generates a body that's immensely profitable for those 100 Specialties of healthare so you know we're living in this this Matrix and this game of you know a devil's bargain between a $4 trillion dollar Healthcare and pharmaceutical industry and a$6 trillion dollar processed food industry that all want us to think that you know the answer is found in a shot and we don't need to change anything about our lifestyle but of course you know these simple habits that we're talking about eating real food moving walking Etc getting out in the sunlight um rapidly can inrease our mitochondrial capacity and um you know are just the most disruptive thing that we can do you know in our culture today is is learn about metabolic health and improve it and um it's it's just interesting to see what's happening in the media with sort of the assault against these empowering habits and very in favor of uh a medication like OIC and then when you trace you know unfortunately incentives there a huge percentage of these Outlets that cover you know OIC as a miracle drug their bills are paid by Pharma 60% of mainstream media advertising budget is Pharma and so you know I just I just say that because I think um it's it's a scandal um that we give so much air time to these medications and not to simple metabolic habits that can make us feel you know so incredible and and really change our core biology so walking exercise eating minimally processed or nonprocessed Foods um you also mentioned temperature yeah very very interested in that but uh before we we go a little bit further down the path of what one can do in terms of um having agency over their metabolic Health um I just feel obligated to just entertain the possibility presumably somebody who's really struggled with their weight a long time um maybe because of excess Cravings you know challenges in regulating their appetite or whatever we don't know what the reasons are um maybe they injured their knee and they can't exercise I mean this happens right um at least not yet um take a GP analog like OIC loses some weight probably loses some muscle also one would hope that that would give them the sense okay now I can move my body better I'll start exercising eating better as well I think that I have to imagine that there's a middle case condition where people are not just relying on Pharmaceuticals and not just relying on um behavioral uh routes uh to improve metabolic Health but can do both right I mean that and one would hope they are if if they're already taking these meds or is it the case that when people have a pill or an injection or a potion that gives them the effect that they want that they just remain sedentary I think we have to look at history here I mean you first of all there have been other weight loss medications throughout history that you've talked about in the podcast like the fenfen and then there was another one I think even before that that made people their temperature go up that you talked about so the two these are I used to work on thermal regulation as an undergrad so uh fenfen was eventually banned because it caused some cardiac issues I believe it was a stimulant F Flur me so um sorry it's not Fen Flur me it alone it's a combination of things that's why it's called Fen Fen um and then um dinitrophenol right which was um based on the observation that workers in ammunitions factories were being exposed to this stuff and losing a lot of body fat and weight um it actually made its way into the sports Community it's highly deadly highly deadly just don't even don't even look it up it's highly deadly don't because the moment people start looking it up they started thinking about dabbling the way the internet is now dinitrophenol um and I think it has to do with with um sort of uh processing of the of mitochondria I think this is happening in the the electron chains in mitochondria so anyway or free electron look it up excuse me um the bottom line here is that um there have been plenty of drugs mostly stimulants used to help people lose weight and um or that have acted directly on the mitochondria it has not worked out well historically it just hasn't and I think that I'm not just going to lump it's a different mechanism so I don't want to lump it in with past weight Lo loss drugs however if you look at the trends throughout history the medicalization and pharmacology towards chronic issues has been an abject failure I cannot I don't know of and I'm sure people can correct in the comments but of a single chronic condition for which the explosion of the pill to treat and manage that condition has lessened the rates of that condition the more ssris you prescribe the more depression we have the more metformin we prescribe the more type 2 diabetes rates are going up the more OIC is being prescribed obesi is going up you know this is on Wall Street they're not this is on track to be a blockbuster drug and they're not assuming the rates of obesity are going to go down that wouldn't actually make sense for the business mod model I mean these are being talked about at the JP Morgan Healthcare conferences do you think they're thinking that this is going to plummet no like there are I can't think of very many chronic conditions for which the explosion of the medication has reduced the frequency of the disease that's really something to think about um and the reason is because of exactly what we started this conversation with they're not actually truly impacting or healing the root cause physiology in some cases they're worsening that root cause physiology like they are inducing oxidative stress they may help with the symptomatic management um but not actually reducing that Trifecta that we talked about in the beginning and so why do we have reason to believe that medicalizing obesity and not actually getting at the root cause which has to be impacted by multimodal gent gentle nudges in our daily life habits and environment that that's actually going to reduce the rates of the conditions so no that's very helpful okay so I'll then return to the other question about temperature uh what are some things that can do with temperature and by the way as I do this I I can't resist any longer uh Casey Dr means brought me this jar of blueberries people that know me know that I um I'm a driveby blueberry eater so if there's blueberries out on a on a table I'm going to take some I've never eaten during a podcast but I'm going to now so um I'll try and chew quietly do you want some sure okay um um I love blueberry Beres and um no I don't eat them one by one so I'm but I'm going to try and eat them quietly so we'll keep them here in the middle for the time being and I'm going to eat them by the handful just cuz I got hungry and and you mentioned berries earlier and it triggered a a neural circuit for me so what about temperature people that know me or even that just listen to the podcast know that I like the cold shower thing cold plunge thing I don't do it every day I don't do it after resistance training workouts for at least 6 hours and mostly keep it on days separate from the resistance training because there are some data that can inhibit hypertrophy and strength um adaptations but I like it I like it it feels good um I feel great afterwards for many hours and I I believe there are some health effects and um I'm willing to weather the storm uh of of naysayers because more and more data keep emerging that that's the case um not all the data are spectacular yeah one paper on this actually was just retracted we need to do an update um to an episode to um it's not work from my lab but I still think that there's a lot of really terrific work on um deliberate cold exposure what's the deal with temperature and mitochondria so no one has basically described this better than you I feel like on your on your platform but I think about it very very simply throughout human history humans have really in so many different parts of the world been exposed to hugely fluctuating temperatures like if you look at the Sahara Desert or like a regular day in Colorado it's like you can go from let's talk about s deser you can go from 30° to 110 degrees in the span of one day and like even the concept of indoors is like a relatively New Concept in human history four walls you know insulation then Central Heating and Cooling that's like the last 50 75 years in most homes and so this idea our cells have evolved to respond to Big swings in temperature that very recently we have totally pulled away and I think that when I think about the mitochondria and increasing their capacity I'm thinking about well how do I use different energetic signals in my environment to essentially get the mitochondria to do better work and we can think about all the different types of energies that we're exposed to solar energy thermal energy acoustic energy mechanical energy you know food energy like there's there's that's basically what our environment is right and thermal energy is a big one of those we can speak to our mitochondria with the Lang of thermal energy and say hey it's cold outside we need you to print more of yourselves or work harder such that we can create heat inside the body to respond to this stimulus and so that's kind of the framing that I use for it and like you know this data is hard to know if it's totally accurate but like our population is is Cooling and some I think it was Data Stanford actually that was showing that like our temperature has gone down like 2% or something like that in the last 100 years and that fundamentally is mitochondria not working as well as they should research has shown we're making less ATP in a lot of our cells and that's you know function of mitochondrial dysfunction one fun fact I don't know if you knew this but uh the body makes about 88 pounds of ATP per day for like the average American so we're constantly making it we're constantly recycling it in this like you know like basically make it use it make it use it make it so fast that like we essentially don't change our weight but but it's kind of and of course as it's being broken down HP to ADP we release heat and so I just think of cold as like one of the tools in our tool belt to talk to the mitochondria to say make more heat and in a world in which our mitochondria Under Siege I think it's a valuable often very inexpensive one that can we can use of course it does not supplement or replace food sleep exercise but I think it can be a very valuable tool to stimulate you know through that signal to to basically make more heat and you know we know of course it can help and it the data you know is is mixed but like incre increase Brown fat which is like mitochondrial dense fat and have it do more work and whatnot so ultimately Brown fat is mitochondrial dense fat and we want to you know help promote that so that's how I use cold and then on the heat side you know just fascinating how that's kind of acting to help metabolic Health um through the activation of the heat St protein some of which have you know the ability to upregulate antioxidant defense systems and quell some of that wildfire that we talked about that can hurt our mitochondria so um I put them lesser on my list um but you know because we just can't we can't avoid the food and you know the sleep and and the movement but I think it's a great tool that we can use I love it and I will just point out that the reason the brown fat is Brown at all is because of the density of mitochondria it's literally Brown down the microscope this is not the kind of fat that um is subcutaneous although it you know it sits around the scapula neck upper back there's other um pockets of it on the body too and such an interesting tissue um yeah I don't know why deliberate cold exposure is so controversial I think it's because people who don't like it and frankly no one likes getting in it the the best part is getting out and how you feel afterwards but I think it um nothing Gres on people uh like deliberate cold exposure if they don't like deliberate cold exposure and there's no requirement for it but I think it's a very interesting stimulus and I think there's also a very interesting relationship between light and temperature because in most areas of the world as days get longer meaning more sunlight available temperatures go up um and nowadays we can really divorce ourselves from all this like day lengthening and shortening temperature fluctuations which is not to say that we should all be running around in a minimal amount of clothing Outdoors but there's just such beautiful data from Dr Susanna soberg work um showing for instance that deliberate cold exposure then leads to one feeling more comfortable at cold temperatures because you become a you know a essentially more of a furnace more more more Brown fat anyway we could go on and on but I think it's um yet another lever of of of autonomy in terms of taking control of one's Health as you said um not as critical as food intake and quality amount and maybe timing as well um speaking of timing what are your thoughts on fasting and then of course movement and exercise yeah the way I conceptualize the idea of fasting obviously this is one where we we need more work right because the word fasting is so limited there's so many different parts of this but skipping breakfast for me would be that or or skipping dinner sometimes I'll skip dinner sometimes I'll skip breakfast right um I think that some of the most interesting data that I've seen has been about if we reasonably compress our eating into daytime hours during the heart of the dial cycle when we are supposed to be eating so essentially matching our chronobiology with our Behavior which you know we are dial organism so we kind of need to respect that like when we do that and we compress it in a moderate way our metabolic health is better and so some of the studies that have looked at this one that was interesting was and I think very hopeful for people is that if you take all the food all the calories that you're going to eat and eat them in a sixh hour window versus a 12-hour window totally same amount of calories exact same food this is a controlled experiment people who eat the same amount of calories in a six-hour period are going to have much lower statistically significantly lower glucose uh 24-hour glucose and insulin levels compared to people who just space it out over the course of a 12-hour period and it makes sense because if you're spacing that food out over the course of 12 hours that is a different biochemical millu in your body throughout the day it's kind of similar to The Walking you know it's like you are then stimulating insulin several more times you are exposing the bloodstream to insulin and glucose just more throughout the day um and giving the bloodstream less of an opportunity to sort of be clear from that glucose and that insulin and so compressing our eating Windows seems to be helpful uh for for metabolic health and it's a bang for your buck right like you can eat the same amount of food you just have to eat in a shorter period of time so for people who want to eat you know a lot maybe just consider compressing it into daytime hours six to eight hour window yeah for me six is tough the one meal per day thing is tough I have friends like Lex Friedman that do the one meal per day I end up eating so much food at that meal I experience a lot of like kind of like mechanical distress it's typically later in the day I think an 8 to 10 hour window has worked well for me most most days um I know as soon as we talk about intermittent fasting which is what or Tim restricted feeding same thing which is what we're talking about right now I'm sure somebody's going to call up the um there's been a study that's been circulating about a um massive increase in cardiovascular risk in people doing intermittent fasting in particular the six-hour feeding window I just want to point out we study as far as I know I could be wrong but as far as I know that study is still in abstract form it's not yet peer-reviewed yeah it's like the fact that um studies that haven't been peer reviewed aren't even close to being peer-reviewed are um are being like put out there as news stories is is really problematic because um I can tell you as somebody who sat on the editorial Boards of many journals for many years I still sit on a few reviewed countless papers I've submitted and had to deal with reviews on countless papers the fact of the matter is like until the reviews are done the revisions are made like that paper may never see the light of day and it may end up in a journal that you is barely worthy of a placem it might end up in a high tier high quality Journal but it might not so because there was quote unquote a study done means very little but it means especially little maybe nothing until it's peer reviewed absolutely and the methods were very poor in that study it was a recall based study I think for two days of of recall of people's diets which is notoriously very bad in terms of accuracy so yeah and I think I'm not in any way suggesting that a six-hour window is the optimal window I'm just sharing the data that suggests that compressing the window uh seems to have a favorable effect and I certainly don't do six hours but I think when you look at what the average American is doing which is the average American has 11 eating events per day and 50% of Americans eat over a 15h hour window per day I can recall those because I remember when I was writing the book I I was like that's a long time 15 hours and 11 events and and every time you're doing that you're going to be stimulating this glucose in the bloodstream explo exposing the blood vessels to that glucose you're going to be turning on all the pathways with insulin to basically store it or you know and it's so it's it's strain for the body and so I think giving the body times intentionally to allow insulin to come down and to allow glucose to come down what that does is it generates metabolic flexibility it gives our body an opportunity to have space to use accessible glucose and then convert into using stored fat but be and that ultimately is metabolic flexibility the ability for the body giving the body opportunities to use glucose but then have times when there's not high glucose and Insulin around to actually get into the fat stores and I think one of the reasons why we have such a massive overweight and obesity you know rates in the country is because with the way the culture of eating right now 11 eating events per day eating over the course of 15 hours per day I would imagine the average American body is rarely if ever tapping into their fat stores for energy and a meaningful way because we always have glucose available to the body if you think about again the stats about ultr processed food um about 70% of the the items on the shelves in the grocery store Ultra processed food and those ultr processed foods are built on refined added sugars and refined added grains so we're just we very rarely give the body the opportunity to rest and and move into fat burning and that's where compressing the eating window can be valuable um obviously people have talked about this before but fasting can be a stress for the body especially if your body's not used to using fat for energy and so it's something to ease into and go slow but I think if you're slowing down enough to really hear what your body's signal are saying you can kind of know whether I think your fasting is working for you or not I I can tell I've got too many other things going on I haven't slept well lot of stress I can tell that fasting is kind of making me jittery and not feel good versus if I'm really if I have good capacity I can feel that it's actually making me feel really incredible and so tune in with your body obviously and you know you can check your biomarkers if you have a CGM on you can see what's happening to your glucose if you have a ketone monitor you can see what's happening to your ketones and really actually track which I think makes fasting actually even even more fun I'll mention one other piece of data that I think is actually really kind of fun as well with timing of eating um there was a study that looked at people who ate the exact same meal at 9:30 a.m. or 8:30 p.m. so basically after dark essentially in the part of the dial phase when we probably shouldn't be eating versus early in the morning 9:30 um and the glucose and Insulin responses for the same meal at 8:30 p.m. were significantly higher than when eating at 9:30 a.m. and so again banging for your buck it appears that eating in that earlier part of the day when we're active and our chronobiology is set up for metabolism and activity we have a a lower glucose and insulin response there's also some evidence that melatonin um which is secreted you know as we get closer to sleep um has somewhat of an effect on impairing our insulin sensitivity transient and so we may actually just be not absorbing the glucose from those meals effectively later at night so I tend to kind of move a little bit more a little bit more low carb I I would say throughout the day based on that data and what I've seen on my continuous glucose monitor basically just higher spikes for the same meal later in the day so why not just kind of move it up earlier very interesting something I'll I'll definitely try I tend to push my carbohydrates to a little bit later in the day for sake of sleep um unless of course I've done resistance training which I do three time I aim to do three times a week and post resistance training I try and get some start carbohydrate in me um just to replenish glycogen and that's um then tends to reduce my carbohydrate craving later in the day I love bread and butter bread and olive oil pastas and the other day I found this Argentine place and I love the steaks there but they had Mii that it took everything I had every neural circuit in uh that releases Gaba inhibition to my brain to not order three of those ORD it was so good but you can walk after the no yeah sure I'll allow myself to do those things I'm not super restricted but again I to eat high quality foods by the way these blueberries are amazing um I need to figure out where you got those cuz they're just Tangy enough um I'm doing everything I can to just not take the jar and funnel them into my into my mouth um yeah I think you know if if we're looking at blood sugar blood glucose and Insulin um and as as long as we're talking about that I I did use a levels tracker and yeah full disclosure they're sponsor of the podcast regularly and I I learned a ton I'll tell you tell you what I learned I I learned that um indeed my blood sugar goes up after I eat um that certain foods although the foods that did this surprise me um certain foods tend to spike my my blood sugar um quite a bit um grapes that shouldn't be surprising um Foods food order was very powerful for me I know that the dayon food order are a little bit mixed and it's controversial but um I like to eat like the French I like some soup then I like my entree I like the salad at the end that turned out to have the steadiest um and lowest rise in blood glucose for me and then across time I also found that um I love hot sauna I go um so hot with the sauna that I've been accused by Rogan and other people I'm going to turn myself into a brisket um but um after the sauna my um blood sugar spikes presumably because I'm a bit dehydrated and it's the concentration of blood glucose is that is that possible does that make sense it does make sense but also the heat can affect the accuracy of the sensor itself ah okay so that could be it too but yeah basically what it allowed me to do is make a few adjustments in terms of foods that I eliminated or eat less of food ordering within a meal and I find that I'm very susceptible to um if I don't include enough fat dietary fat in the meal then my blood glucose spikes even if it's just like tuna right but by including olive oil and other things it really blunts it and of course here we're doing correlative um anic data but for me I felt far better when I included a bit more fat um and when the food order was adjusted the way I mentioned before always including a little bit of fiber really helped it and that makes sense right slow the absorption of the food presumably um so I I found that it was a very valuable experiment for me again this isn't an advertisement it just so happens I did this and and really benefited from it um what are some other things that one can learn from continuous monitoring of blood glucose what are some things to watch for that might signal a problem and what are some fun things that one could do to explore an experiment because I like to explore an experiment yeah well I mean a lot of the things that you just naturally learned are the things that have been shown in data and and like you said some of this data it's like small studies small groups of people but for instance adding fat and fiber to meals has a significant and repeatable impact in populations on lowering gluc response uh fat probably in some part due to slowing uh gastric emptying and actually slowing the diges process so the rise in the bloodstream is going to slow down and then fiber both for that reason but also because fiber can in a sense create like a mesh sort of blocking the absorption of some of the glucose that's in the meal so literally kind of actually preventing you from absorbing all of the carbs and we've actually seen that in the levels data set that the more fiber people include with their meals we see essentially a direct relationship with lowering of their their glucose excursions which is really exciting because fiber is something that you can add to meals very easily I put basil seeds chia seeds hemp seeds flax seeds on a lot of my food at this point because it's essentially a little bit of fat a lot of fiber uh and it's kind of just helps you kind of get more from your from your meal um so what you can learn so I think step one the way I think about a glucose monitor first of all I'll say the purpose of the glucose monitor is not to have to game the system and get flat glucose the purpose of the glucose monitor is curiosity it's to start to understand how it's essentially an MRI for how all of our different dietary and lifestyle strategies are creating this readout of glucose in our body which I think can be really interesting and in a world where so many cards are stacked against us with diet and lifestyle and where there's a lot of confusion about what's right for us that can be like very helpful in actually reducing the confusion and the cognitive load of our choices we know that keeping your blood sugar through the course of a lifetime in a low and healthy range so I don't mean up and down spikes during the day but keeping your blood sugar healthy throughout the course of your lifetime is probably the best thing we can do for longevity staying insulin sensitive staying out of the diabetic range and so one thing that the glucose monitor does for us is just us more uh awareness and agency into like what the trends of our glucose are over time as opposed to a literally one Daya Point snapshot once a year in the doctor's office which is what the majority of us are used to um I really love the idea that people who are able to wear glucose monitors every now and again maybe once a year maybe more than once a year they know what their glucose is and so they're never going to walk into to a doctor's office and have a bomb dropped on them about pre-diabetes or type 2 diabetes because you have the data which is ultimately I hope the world that we can move towards for a lot of biomarkers so you can see Trends over time which I think is very valuable one thing that's fascinating in terms of early prediction of metabolic disease is that you can see how long it takes your glucose to come down after a meal so in a normal healthy insulin sensitive body even if the glucose goes way up it should come way down very quickly because the insulin is buying to insulin receptors and the glucose is getting taken up and it it'll lower what is quickly over the course of it should be down by two hours but from what I've actually seen in our like most insulin sensitive people and also in research that looks at young healthy populations you should basically be spiking and coming down Spike about 45 minutes and come down hour and a half 90 minutes to two hours but if this is after sorry after last bite after last bite although it's hard to kind of exactly but yeah is over I would say about 45es to go up to the and thenly now if you start to see that glucose is going up and then trailing very slowly back down to normal maybe taking more than two hours three hours that is going to be one of those early indicators of potential insulin resistance your body's not clearing the glucose but that's not a metric that we use in standard practice at all and I've actually seen myself very insulin sensitive my insulin is like 2.5 and you know if I don't sleep and I am stressed and I have been sitting my glucose will take way longer to come down I have become transiently insulin resistant so I think that's just fascinating to see that so looking what that ultimately the metric that we call that is area under the curve you want a low area under the curve a you see after a glucose Spike so you want to spike and come down quickly that's going to be if you shade the area under the curve it's a small amount if you go up and then Trail off for two to three hours um that's going to be a lot of shading under that curve and high Au is associated with insulin resistance basically another thing that you can see um is essentially glycemic variability and glycemic variability GV is a metric of how spiky your curves are fasinating paper out of Michael Schneider's lab uh at Stanford in 2018 called glucotype reveal new patterns of glucose disregulation totally Landmark study but basically they put continuous glucose monitors on non-diabetic individuals who by standard criteria of diabetes do not have diabetes and he showed that on a CGM a continuous glucose monitor you have these low variability people that are pretty much flat throughout the day with little teeny little teeny Rolling Hills after their meals you have moderately spiky people and then you have very spiky people who are going up down up down up down up down when you correlate those different patterns of glycemic variability in non-diabetic people you find that the spikier they are the worse their biomarkers are metabolically across the board insulin triglycerides Etc so basically they're they're showing signs through variability of underlying dysfunction that you would never know from a standard test those are the people who I imagine are probably going to go on to develop diseases and yet based on standard criteria their doctors telling them that they're fine that they're all the same so he also showed in that study that non-diabetic individuals when you have a CGM on are going into the diabetic range and the pre-diabetic range a fairly significant amount and we would never know that if you weren't um if you weren't actually tracking like a movie of the glucose so that's so glycemic variability um area under the curve those are two things another really interesting thing you can know from a CGM is Dawn effect so Dawn effect is basically a term in the literature for how high your glucose Rises right when you wake up in the morning I don't know if you noticed this when you were wearing a CGM but some people notice that the second they wake up their glucose jumps up 5 10 20 30 points What's Happening Here is that the cortisol Awakening response to actually get you to wake up and get out of bed that cortisol can cause you to dump a bunch of glucose from your liver because it's basically saying stress hormone cortisol we got to get up we need glucose to fuel the muscles let's dump a little glucose so it's it's normal but what the research shows is that magnitude of dawn effect is correlated with insulin resistance so the more the dawn effect you're getting I think it can signal maybe the more stress you're under the more cortisol you have floating around how big your cortisol Awakening responses but also if you imagine if you're dumping all that glucose from your liver and your cells aren't taking it up well because you're insulin resistant that that response that Dawn effect is going to be higher so I I don't have the numbers right in front of me but typically I I would want to see a dawn effect I think of like less than 10 points so you wake up and you you may very well see a rise this is absence of any food yet and you do not want to see that going up 20 30 40 points um some people see a little bump again with caffeine in the morning because it's more cortisol and so that's another thing that standard stuff would never tell you so those are kind of some of the looking at early predictors of metabolic dysfunction more of the fun stuff is like actually just figuring out like how is food affecting your body and this is where people really enjoy it and like figure out like oh my God this food that I thought was healthy is actually not you know serving me and actually a lot of people I think who are trying to make healthy choices my boyfriend like he when we started dating he started using levels his healthy snack he worked in Venice would be to go to Moon Juice and get oh gosh I I don't want to throw Moon Juice on the bus here but he would get tasty stuff they do but he would get this green juice that was sweetened with dates and it was like $9 and this was like the healthy choice and he saw the second he put on levels that it was causing a huge Spike like 50 60 70 points and then he was crashing um and he was actually trying to make a good decision so now he's he's swapped his snacks out for more like you know grassfish cheese and some flax crackers and maybe like a venison stick or something like grab and go stuff that isn't spiking as glucose but I think it can help people figure out like which foods are doing what I want them to do and which maybe aren't um and same thing happened for so many of our members with oatmeal unfortunately oatmeal instant oatmeal is one of the biggest spikers in our data set for breakfast and a lot of people are making that choice because they think it's heart healthy and in many people it's actually causing a big GL glucose Excursion and crash and then in some other people it's not and so it's it's really helping with um what are the sneaky spikers and then where's the biochemical individuality and there was a phenomenal paper out of um uh um Israel that from from cell about seven years ago called uh personalized Nutrition By prediction of glycemic responses it made big waves but it basically showed that you and I could eat the same handful of blueberries and have totally different glycemic responses so the idea of glycemic index as like a certain amount of food with a certain amount of glucose causes a certain glucose rise it it kind of debunked that and that matters because repeated sustained glycemic variability over time is not good for our health we want to choose the foods or balance the foods that are going to keep us relatively more stable um so that that's that's very helpful just understanding your personal respon to food and then what are the lifestyle strategies you can use sleeping better walking after meals more resistance training cold plunging breath work that can actually serve to modulate the food environment to actually reduce the glucose spikes and people find that all of those things can positively impact glucose spikes especially the walks after the meals but um to fascinating to see a lot of women especially like menopausal women in our community who find that their glucose pattern are getting worse because estrogen's dropping and that's going to you know really take a hit on insulin sensitivity they start resistance training glucose comes kind of right back down so because of the monitor they can feel more confident in the intervention they've chose to do to help with metabolism that kind of creates a virtuous cycle so um so those are some of the big things those are big can I mention one more I'm so I know I love I just I could obviously talk about this all day think fascinating but this is just one more that I think is fascinating because this was a paper in nature from last year that talked about and this might actually be one of the most valuable things to people which is that again talking about Cravings we all want to get off the craving grip this paper in nature showed that essentially when people Spike their glucose with high carb High starchy Foods they'll often have a big crash afterwards and the reason for that is because a big spike leads to a lot of insulin secretion and then you soak up all the GL glucose and sometimes you can actually go below your Baseline so a small Spike usually won't lead to a crash but a big spike often will that's called reactive hypoglycemia postprandial hypoglycemia a lot of people think they're dealing with hypoglycemia when in fact what they're really dealing with is that they're spiking their glucose too high and then they're crashing I see and the paper showed that the extent of postmeal dips the crash after the spike was pred predictive of 24-hour energy intake and cravings for carbohydrates and this makes sense if you crash low that is a signal to your body we have to get our glucose back up and it it will drive you to eat high energy foods carbohydrate rich foods and Cravings so one of the best things we can do I I believe from my personal experience from Members experience and with some data to support this is that one of the adjuncts we can use to monitor our to manage our Cravings is actually to like lower the the the extent of our spikes so that we crash less and so that was a fascinating study looking at CGM data that's interesting so the cgms can reveal things not just in the immediate meal period but can relate to sort of Downstream uh consequences yeah again I found it to be tremendously useful I'm so glad you mentioned sleep by the way I'm going to resist the temptation to Rattle off 20 studies showing that oh god um you know even having um too much bright light in a room while one is sleeping at night even dim light which is you know I don't want to scare people into thinking they have to sleep in complete darkness although an eye mask can be can be great um can alter uh morning blood glucose levels in I believe it was adults and kids as well this a study in proceedings in the National Academy of Sciences uh have to go back and check if it included kids but um pretty striking and then it's there's something very clear about the fact that when people get the early night sleep of four to 5 hours but then don't get the dominating um you know last hour or two of sleep in the morning that resting blood glucose is is altered it's so interesting to think about what's going on in sleep there's at least one paper that I'm aware of where they had people breathing into a tube during sleep to measure what sorts of um met metabolism they were undergoing and it's interesting during a full night's sleep um all of us seem to transition between um different forms of metabolism I'll send you this paper it's really it's really cool and I'll put a link to in the show note caption such that at one portion of the night we're met we're rely more on let's just call it sugars for a sake of Simplicity other times we're more Ketone dominant there's a a market shifts in metabolism throughout the night it's almost like the brain and body cycle through all the different modes of of metabolism throughout the night and then almost like a rehearsal of the metabolic pathways if you know we can anthropomorphize a bit here but then if um sleep is truncated it clearly has an effect on daytime uh fuel regulation um just so interesting so um getting sufficient sleep getting quality sleep is is absolutely key there's a lot for people to pay attention to but you've given us a lot of tractable avenues for people to do that um that are mostly behavioral there's a few don'ts but mostly some dos yeah yeah we haven't mentioned that um you know you don't need to even perhaps belong to a gym it's like and with the cold uh exposure thing I always say you know if anything it'll save you money on the heating bill so um there's a there's a literally NE potential negative cost there um I think levels and other cgms are really interesting and value um to experiment with what sorts of other stuff is going to soon be monitored in our blood because for instance I would love to know continuous hormone levels lipid levels blood blood sugar levels I mean are we moving past um just blood glucose and are are there soon to be other um things in these monitors so that when we and by the way if you haven't used this it's really cool you just take your phone you scan it over the the sensor and then it basically gives you a chart graph of of what's going on in your bloodstream and now they're all the latest gen of each of them are all Bluetooth now so no more scanning which is kind of nice and the answer is yes there're are several different um analytes that we're going to be able to track and uh Abbot which is one of the three main manufacturers of cgms has announced that they're they have a new product called the lingo which is going to actually be able to measure ketones lactate and alcohol um continuously which is pretty interesting from like a metabolic comprehensive metabolic standpoint different sensors for each not all in one so I think we'll have to like polka dot ourselves if we're tracking all those things um and then Dexcom which is the other main company that makes cgms has just announced they're coming out with an over-the-counter non-prescription version of a CDM CGM called the Stell later this year so there's exciting things happening in the industry and I I really do think um continuous monitoring it's it's going to expand to a lot these other things that you're talking about hormones Etc and I mean it it it really needs to I think that um you know snapshots of dynamic system are just never going to really be able to give us a full picture on what's going on and um what we really want to be able to do to dig our way out of this Health Care crisis I think is is empowerment individually and understanding how this rapidly changing environment is affecting our own biology so we can make the targeted choices to hopefully change the environment to be more conducive to Cellular health and continuous monitoring is a closed loop bio feedback that can that can help us with that decision- making and and essentially predict failure of the system rather than wait for failure of the system before we do something about it so yeah I think lot's coming down the pipeline love it yeah let's talk a little bit about mindset this is a really interesting topic that you included in your book we've had guests come on and talk about growth mindset stress can be enhancing mindset I'm big on mindset um because I'm interested in how our cognitive reframing or cognitive framing can just change the way our biology works and vice versa of course um but you talk about mindset in a certain context and one of the um favorite passages around that that I really enjoyed was the relationship between kind of like trying to control everything and nature you know like and uh and how uh getting into nature uh itself um can be valuable for us so maybe touch a little bit on mindset if you will and um yeah what are your thoughts on nature literally getting out of doors yeah so I think I think that mindset and more broadly than mindset I think psychology and our relationship specifically with fear and control I think they're probably the most underrecognized thing that is impacting the metabolic Health crisis the chronic disease epidemic there has been data that's looked into this we know that there's studies showing that loneliness impacts mitochondrial function and that loneliness is a risk factor and stress is a risk factor and these things and something really fascinating actually with the CGM data is that many people who wear a CGM I don't know if you saw this but when you feel stressed it actually has a diabetogenic effect it literally causes our blood sugar to go up when we feel stress and that can be a fascinating um unlock for people to realize I kind of feel like I'm okay right now but my body is telling me something different it's telling me that biochemically I'm actually releasing energy stores from my liver glucose to fight some threat that you know I wasn't really aware of so there's there's we definitely understand there's this link here but but it's certainly not made its way into clinical practice so the way I think about it is that what we know about the cells and especially the mitochondria is that the mitochondri more than the PowerHouse of the cell they actually are a part of the cell is constantly tracking resources and threats and are basically modulating energy resources based on that and the threats can be anything they can be a virus they can be and this is all coordinated through this thing called the cell danger response it can be a virus it can be a toxin in the environment it can be lack of micronutrients for the electron transport chain that it needs to do its function it can also be psychological threats because of course our psychological milu translates through nerves and hormones and neurotransmitters and our microbiome to affect our cellular biology throughout our whole body our cells hear every single thought that we're thinking through biochemistry and when a cell and a mitochondria are getting the message that there is a threat or something to be afraid of they are going to change metabolic function towards defense alarm threat response and away from repair homeostasis build building essentially thriving so our and and and I think what's really maybe the most unnatural thing about our modern world you know the food of course is unnatural 70% is ultra processed but we also have this device in our hands literally with us all the time streaming fear inducing media into our brains and eyeballs every waking moment of the day if we let it so we're glued to our screens and our devices and right now essentially the traumas and fears of eight billion people all over an entire Globe are now ours to process and our cells and our mitochondria there is no escaping it they are going to respond to that and so I think a big part of the metabolic Health conversation is how do we create a sense of safety in our bodies no matter what is happening out out side of our bodies and this can come down to every person's Journey will be different for this because the things that cause a sense of threat or fear for any two people are going to be different and I think some of the main categories is one unresolved childhood trauma like something that I think is getting a lot more talked about these days but like what's embedded in our nervous system these limiting beliefs and memories that are really wired that create a sense of hypervigilance in US sort of all the time what's coming in through our devices our phones our computers the media that we're exposed to that's constantly giving a fear signal and I think on a broader level a big Western one that we don't talk about is literally like existential feel of fear of mortality we have a very Des spiritualized very uniquely death fearing culture like you look at other cultures Eastern indigenous the stoics they all had intense curiosity about death we talk about the cycles of life there's this real engagement with it that we are so afraid of in the in the western system to the extent that our entire healthc care system actually I think you know we've built it around like we're not going to we're we're not going to help you thrive we're just going to do whatever we can to make sure you don't die like that's it's built in everywhere and so we've got the devices we've got the childhood trauma we've got the fear of mortality we have a very poor system of mental health care in the culture and I think that through all these things Americans are getting crushed mindset and psychology wise and that is a big big trigger of our mitochondria essentially diverting resources towards defense threat and alarm rather than homeostasis building repair so again it comes back to taking really honest stock of what are the true fear triggers in our lives across those and others and creating a sense of safety in our minds and bodies no matter what the external world looks like which may mean putting boundaries up to you know the media doing the therapy doing the different modalities what I believe and I talk about in the book getting back to the question about nature is one of the best things that we can do is actually literally just go outside and I it sounds so simple but one of the most astonishing stats I literally found in researching this entire book was that the average American is spending 93.7% of their time indoors wild 93.7 that's in a car or in a building so we are locked in these cages staring at fear inducing media and our mitochondria are like what like what I don't know where to channel my energy it's just I it's short circuiting I think so many things happen when we go outside as you know I mean even what the vision system is doing to our anxiety levels we are getting sunlight which of course for uh for you know complex reasons is very helpful for our metabolic Health separately entrains our you know chronobiology and uh you know light light from the sun as an incredible regulator of our mitochondrial function um but it also it's our best teacher you know when we're out nature and we really look at how beautiful the world is and the cycles of nature we see the cycles of you know the the seasons and we see the awe of the sun and the trees and just this all this Alchemy that's happening outside of us we see you know spring to Summer to fall to winter we see the tides moving in and out everything's in phases and I think when we reflect and meditate on all the cycles and the polarities in nature night and day cold and hot new moon you know quarter moon full moon you know all these things it's actually it it entrenches on a subconscious and conscious level that there is a fundamental Harmony and pattern to the world we're living in that is bigger than us and that is fundamentally good and beautiful um and we are locked inside of the Four Walls of our house I think we get very scared we get very controllable and the system wants it that way because when we are scared and when we are existentially afraid we will literally do anything we will buy anything do anything watch anything that will in some way ameliorate that pain that we're feeling and we will take any pill we'll get any surgery anything that makes us feel like we're controlling this seemingly out ofc control situation and that's what drives us into all the dopamine Loops you know the the social media the process food the porn the gambling the alcohol all of it it's all to amate I think ultimately fear and I think yeah I think by actually really just spending a lot more time try and get that 93.7% down to like 50% spend as much time as you can outside we know that people who spend more time outside are metabolically healthier and I think it's for pleotropic reasons but I think one of it is that it is the ultimate convincing of abundance and fundamental abundance in our world and of awe which I think is really the antidote to fear and that has a profoundly soothing effect on our psychology um and the sense of scarcity that drives a lot of the decisions that actually make us unhealthy it's fundamentally rooted in in scarcity and I think also when we realize we are part of nature again going back to that doubt statement we're a process not an entity realizing like you know all the trees around us and we take that walk even in a city we see all the trees all those plants all those leaves are making the oxygen that process that that literally let us do oxid of phosphorilation and that sun and that leaf on the tree the sun's energy is literally being stored in the carbon carbon bonds that the plants are generating in photosynthesis that ultimately all metabolism is is unlocking the potential energy stored from the sun to create the human energy that lets us love and move and live and think and do all the things we love to do and then it just becomes so obvious like of course we have to like eat real food and of course we have to not poison our soil with pesticides and of course we have to like you know care about the environment and we have to get outside and move and we have to be in the sunlight during the day because we are the environment we are a process that's constantly in Dynamic conversation with it and um I think I think a lot of people will find that their health gets a lot better if they spend radically more time outdoors and I think a lot of people might say well I can't I work on a computer and I'm like you know Rome is burning like we're sick as hell right now we need to get creative like move your computer outside take a walking meeting open your mail Outdoors chop your vegetables on your balcony at your apartment like we we have to find a way to connect back with our source understand that the world is abundant and harmonious uh re-enchanting from that sense of gratitude and awe and that will lead us right where we need to go which is um a really I think joyful experience of our health Journey um that's rooted fundamentally in connection rather than us being siloed from all of this which going back to the beginning of the conversation that's fundamentally what's wrong with the Healthcare System it's silos and we have siloed oursel from all of the life-giving things in our environment and that has ultimately leted us to be very very very sick and we've just I think we got to go back outside so that's one of the things but there there's many other things we can do to change those our relationship with fear but um we can't change the world as a whole but we can change what happens inside our body in terms of how we respond to it and for our mitochondria we have to we have to create a sense of safety in our bodies for our mitochondria to do the work we need them to do for health I love it and I love it for many reasons I I think um it was my I know it was my friend and former guest on this podcast Rick Rubin who several times early in our friendship he said um Back To Nature the only truth um and I asked him what he meant by that and you know cuz Rick can be a little bit um cryptic sometimes um not always but sometimes and what he was saying is you know it's a real thing you know you can immediately feel the connectedness between The Human Experience and um life of other types plants animals you know sunlight the circadian rhythms and the and the rhythms of the of light and dark um because they impact us so powerfully I mean if if there were ever a force in the world that impacts how we feel it's the Circadian rhythm it's the rising and setting of the sun it's um the impact of light and dark and then all the other things that you talked about today um I can't help but reflect on kind of your take on kind of what a lot of not all but a lot of U modern society attempts to do um it attempts to do a lot of good things too I believe I'm a Believer in technology um but that it if I were to translate it sounded like um what you were saying is that it gives us a sense of loss of control by instilling fear like we don't have control and then um there are a number of let's just call them programs in the world um that then sell back the illusion of some sense of agency little by little right a temporary agency and then puts you back into the cycle and there's something about going into nature which just um removes one from all of that at least temporarily gives you a more basic understanding of the relationship to self and things around us even just looking being able to see it to a distance we know is powerful for the the brain reducing anxiety we know being outdoors for 2 hours or more per day reduces myopia nearsightedness this is independent of all the other effects of of uh circadian rhythms Etc anyway and on and on so I second and third and um and uh here here all the um all the statements you made before I also just have to say I I really appreciate how you are able to tackle the cellular biology the molecular biology the macroscopic things that we can all do walking resistance training um cold exposure sleep um high-intensity interval training um and make make a case for each and all of those as it relates to the underlying biochemistry and weave all that together in a way that then uh you beautifully wrapped into this idea of connecting to Nature and not divorcing ourselves from Modern Life but really looking at the ways in which certain components of Modern Life are really making us sick not just the the behaviors not just the dos and the don'ts that it's kind of imparting on us but also so kind of the psychology around it it's uh that it is quietly but powerfully oppressive is is the message that I'm getting and that we have to take a stand against it and the way to take a stand against it is to do what are very um basic and fairly easy to access things making better choices about food timing quality amount exercise and on and on so so I'm running long in my response to your much more eloquent description of mindset uh but what I want to say is on behalf of myself and everyone listening I so appreciate we appreciate the work that you're doing to be a medical doctor specialized in one of these silos and then to take a step out and say nope not me I'm going to do what I see as best for the greater good in terms of giving people tools giving people a sense of agency and autonomy to take control of their health this is in some ways a heretical idea um but luckily the numbers of folks like you are growing and you're a real leader in this field um by example and by the incredible work you're doing with technology and information sharing love love love the book I did go through it um front to back um I haven't tried the recipes yet but thank you for bringing the blueberries I'll try the recipes um at least one of them and um I just want to thank you for sharing what you do and um for continuing to do what you do we we need it and we appreciate it so thank you 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