Cortisol's Impact on Health and Diet

You are in for an amazing treat. We're being joined by Georgie Dinkoff, who is an advocate of bioenergetic medicine developed by Ray Peet, really rescued him from his personal health problems. I've learned so much this year. He's just opened my eyes to so many foundational basics. We are gonna dive deep into the science. I think there is hardly a chronic condition where you cannot look at the condition and don't see cortisol implicated. And usually, in the majority of cases, it is elevated cortisol versus the low cortisol. I think it's a very good argument that cortisol is catabolic to the brain. And clearly, if it's catabolic to the brain, it's probably not going to improve your mood. If anything, it's going to worsen it. If you don't consume a sufficient amount of glucose, you will, of course, raise cortisol at night. It has been shown that cortisol levels... do not decline with age unless you really have adrenal failure, while the levels of all of these anti-cortisol youth-promoting hormones declines with aging. Multiple intervention studies have demonstrated if you administer agents that oppose cortisol, block it at the receptor level, or reduce its synthesis, you can achieve really good health results and also the way you look. There's many clinics around the world that treat and even cure type 2 diabetes. by putting diabetics on this really restrictive diet until they lose most of their fat. And then suddenly the metabolism of glucose gets restarted. So I think this directly shows you that the problem with the glucose wasn't the glucose itself. It wasn't the glucose that was fattening them up and the glucose that's causing the problems, but they had too much fat in their bodies. Once you get rid of that fat, no matter how you do it, the problems with metabolizing glucose disappear, which to me is a great test about the Rando cycle. who is just beyond amazing. Thank you. Thanks for inviting me again. Hopefully the information we put out there is useful and people can improve their health. So from our very first conversation, what literally blew my mind was the information you shared about cortisol. Of course, everyone knows about cortisol. We've certainly taught about it in medical school. And if you look it up, you'll see that cortisol... is responsible for glucose homeostasis is what they typically for regular glucose levels. But they, you know, well, that's true. It really doesn't explain what it does. It's a rescue hormone and its primary function. It's a glucocorticoid means it's the first part of it is glucose. That's what it does. It increases your glucose levels because if you go too low, you will go into hyperglycemic coma and you are dead. So it's, it's a rescue hormone and thank God it's available. It's only secondary component is an anti-inflammatory. So what Georgie explained is that when your glucose levels drop, you have to do this and to shred your protein. It's just, it's a very highly anti-catabolic protein. And I was listening to one of your podcasts this morning, Georgie, where you explained that the primary benefit of anabolic steroids to build your muscle mass is that it's anti-cortisol. That's how it works. It's like, oh, who would have known? You would have thought it had some direct action on the muscles directly, but no, it's anti-portisols, like mind blown again. This is another mind blowing that does this, but it's also the primary driver for aging. It is the hormone responsible for accelerating your aging process. And one of the reasons I got into this, and most people are biohackers, is that they want to throttle that down. throttle it back so you're slowing the aging process yet virtually no one and i know almost every major leader and thought leader in this space and i've never really heard anyone talk about this this is this is like mind-blowing information so with all that massive introduction i don't think i've ever given a longer introduction before an interview to anyone but this is going to be a long interview so it's worth it just to frame it so why don't you comment on what i just said I mean, I fully agree. I think there's hardly a chronic condition where you cannot look at the condition and don't see cortisol implicated. And usually, in the majority of cases, it is elevated cortisol versus the low cortisol. In fact, the only situation where you have low cortisol and it becomes problematic is probably Addison's disease, which is truly adrenal failure. And that's rare, very, very rare. In fact, the only high-profile person that I know that had it was President Kennedy, John F. Kennedy. And he took for life, I think he took cortisol injections every couple of days. But for everybody else, now, if you look at John F. Kennedy, even with those injections, he basically was in a state of relative cortisol deficiency. But if you look at him, he looks remarkably young and handsome. Not that he was very old when he became president and killed, but he looks younger than what other people at this age look like. And especially people at this age that are, if you look at them these days, they're going to look on average a lot older than JFK. And studies as far back as the 1950s and 60s demonstrated that you can produce every single phenotype of aging if you inject cortisol or at least create a state of relative glucocorticoid excess in the animal. So you can do that either by injecting synthetic or natural glucocorticoids, or you can do it by reducing the levels of the natural anti-cortisol steroids in the body. And those are pregnenolone. progesterone, DHEA, but in males, testosterone, and also dihydrotestosterone. So if you reduce the levels of those anti-cortisol steroids and keep the cortisol levels normal as they are in the animal, you will still achieve the same kind of like the phenotype of aging. And that's actually pretty much what happens to people as well. It has been shown that cortisol levels do not decline with age unless you really have adrenal failure, while the levels of all of these anti-cortisol youth-promoting hormones... declines with aging. Prenatalone, DHEA, progesterone, by the time you're 80, their levels are at about 20% of what they used to be when you were in your 20s. So really what happens is that cortisol stays the same, but basically your relative state of cortisol increases because there's nothing to oppose the cortisol that is already there. And multiple intervention studies have demonstrated if you administer agents that oppose cortisol, block it at the receptor level, or reduce its synthesis. you can achieve really good, you know, both health results and also the way you look. The anabolic steroids are probably the best known example. It's really a misnomer because they're not anabolic. They're actually anti-catabolic. Muscle has one of the highest expressions of the glucocorticoid receptor through which cortisol shreds the muscle. It binds the receptor. It increases a number of different proteolytic enzymes. I just got to know muscle is the highest. It is? Really? And gastrointestinal tract and brain. So these are the three places where the receptor is the best. So cortisol actually shreds your brain tissue too? Exactly. And it causes massive brain atrophy. And it's been well established for the last five decades that cortisol can actually cause depression. People with depression have smaller brain mass and brain volume than people that don't have depression. This was probably one of the most convincing arguments to classify depression as actually as a... physiological condition in addition to being purely mental as well. They looked at MRI scans of people with depression. They saw they have, depending on how severe the depression is and for how long it went untreated, these people had much smaller brain volume and a number of brain cells as well, number of neurons. So they said, okay, can we form the hypothesis that maybe cortisol can cause depression if it's chronically elevated? Let's test it. Let's administer an anti- cortisol medication to animals and people and see what happens. Within 48 hours of the glucocorticoid blocker, RU486 being administered to people with clinical treatment-resistant depression, they experience remission. So I think it's a very good argument that cortisol is catabolic to the brain. And clearly, if it's catabolic to the brain, it's probably not going to improve your mood. If anything, it's going to worsen it. Well, thank you for that. And I think, so ultimately... As I mentioned, when your blood sugar level drops, that's a trigger for you to increase cortisol. This is the last thing you want to do. Really, one of your primary goals in achieving optimal health is to literally limit the elevation of your cortisol, much more dangerous than sugar level elevation, which almost everyone is focusing on. They've got monitors, the 24-7 glucose monitors, continuous glucose monitors called CGMs. that you can wear, and pretty much every five to 10 minutes, you're going to get a reading, because they're so concerned how dangerous glucose is. But that's not the issue. The issue is cortisol. Yep. And fats, right? So if your blood glucose is rising... They're connected. That's what we're going to talk about. They're connected. So instead of asking, okay, is elevated blood glucose a symptom or a cause of the pathology? So far, we've only been told that, hey, high blood glucose is the devil. You got to have everything in your power to lower it. However, all of the drugs on the market, especially the more recent ones that actually target lowering HbA1c, the glycated hemoglobin, all of them increase all-cause mortality. So clearly, messing directly with the levels of blood glucose, it's not something you want to do. You may temporarily decrease the biomarker, the glycated hemoglobin, but it does not mean you're getting healthier. There was a famous Harvard medical professor who said that the moment a biomarker becomes a goal, it's easiest to become, it's easiest to be a biomarker. So you're starting to chase something that's just a symptom. And unfortunately, for many conditions, simply because medicine says that they don't know what the cause is, then you're kind of relegating yourself to symptomatic treatment. And that's really what most of these blood glucose lowering drugs do. They may lower your blood glucose, but they may kill you in the long run faster than the elevated blood would have done by itself. I just want to make it clear that we are not saying that it is not important if your blood glucose is elevated, but it's a symptom. It is not the, you don't want to hit that directly. You want to address the fundamental foundational cause and then everything else comes into place. And just to give you an example, when on my first interview with you, I was still relatively high fat, 70, 80% fat. Now I realize that wasn't a serious chapter. Fortunately, I could tolerate it. I didn't have too many bad side effects, but it wasn't optimizing my health. Now I am down to like 27% fat and like 57, 58% carbohydrates. And so having said that, you say, oh my gosh, you must be diabetic. So no, I lost five pounds more. I really was a healthy body weight. And my blood sugar, I just hadn't been done. It went down. My fasting blood sugar went down 10. So. You know, it's not, that's just to me, personal anecdotal proof that it's not the carbohydrate ingestion. It's that what's happening at the mitochondrial level. And to help us understand that I created a graphic because this science can get somewhat complex when, when Georgie describes it. And I just thought having a simple graphic. Now you can look at this, it looks complicated, but when we discuss it, it will be okay. So basically it shows that you only have two primary fuels that you can burn in your body, food, and that's fats and carbs. And the fats are broken down from a process called beta-oxidation and ultimately wind up going to acetyl-CoA, which gets fed into the Krebs cycle. Now, carbs are different chemical structures. So they are a six-carbon molecule. And when they're broken down, they break down to pyruvate. And this is really important because pyruvate then can also turn into acetyl-CoA, but it has to be enzymatically changed through an enzyme called pyruvate dehydrogenase, PDH, or some people call it PDC, pyruvate dehydrogenase complex. So when this complex or the enzyme itself is inhibited, we've got major problems because glucose can, you know, the substrate pyruvate cannot go into the electron-sense point of change. And instead it has to go backwards, not really backwards, but to another pathway, a primitive pathway. pathway, one of all the central single cell organisms and bacteria and such. And that is glycolysis, where it essentially anaerobically ferments that fuel to create energy. And it's very inefficient. It doesn't create a lot of ATPs. And the lactate molecule itself, when produced in large quantities systemically as a result of glucose being shunted, will cause wreck havoc with your system. Your body has a metabolic switch. In many ways, a switch is a switch very similar to the one on a railroad track, where the train comes along and then you throw the switch and it goes down a different track. It can only go down one track at a time. You can't do, the train can't split itself in two and go down both tracks. So there's a switch. And actually, this switch has a name. It's called the Randall cycle. It essentially describes a process where your tissue can only burn one fuel at a time. It can't burn fat and glucose at the same time. And glucose is the same as a synonym for sugar. So the threshold appears to be, and this is different for different people, but it's about 30%. And what do I mean? If your fat level is above 30%, and you're not going to be able to take that sugar, that glucose, and run it through your mitochondria, which is a small organelle within almost every blood. in cell in your body, except for the red blood cells, that produces cellular energy in the form of ATP. That's really one of the primary differences between higher order organisms and lower order ones like bacteria. They don't have mitochondria, we do. And it's very efficient at creating energy. However, if your fat content, the percentage of fat that you're consuming in your diet is over 30%, then this sugar is backed up and it can't go through the mitochondria. It has an alternate source. That alternate source is called glycolysis and essentially is very inefficient. You can take one molecule of glucose and you only make two, two ATP. That's it. And it also doesn't require oxygen. And then so we think, well, that's great. It's not going to create many reactive oxygen synthesis, which is actually quite to the contrary, because it's so inefficient, it's going to create a lot more. reactive oxygen species. And we'll talk about that in a moment. So if your fat level is under 30%, And in some cases where there's some pretty severe metabolic inflexibility, like obesity or diabetes, that level may have to decrease to 15 to 20%, which is pretty extreme. That's a pretty low-fat diet. I don't think it ever really should go under 10%, but the lower you can go, the better that you can tolerate. Usually diets under 10% fat are going to be very hard to tolerate. It's just not doable for most people. But if you... the threshold appears to be 30%. If you have less than 30% of your total calories as fat, then the glucose that you're ingesting can be used efficiently in your mitochondria. And we'll talk, there's some different ways that you can burn that even within the mitochondria if your fat is less than 30%. And we'll talk about that in a moment. But that's the primary principle is you got to get the fat level right first, first and foremost. And then you can hope that you're going to have a chance of burning this. The ideal ratio is not really known, but the epidemiological studies kind of show that about an equal percentage in terms of calories is probably optimal for long-term health, unless you're trying to tackle a specific... Equal of fats and carbs? No, no. I'm saying 33%, 33%, 33% for a healthy person. No, here's where I would respectfully, very respectfully disagree, because... And that's in the whole of the discussion is the protein. I've got so many insights from you, but most people don't get it now. but you can get too much. So like in my case, you know, I have some kidney challenges because of mercury fillings that I had removed incorrectly 30, over 30 years ago. And as a result, I have to be really, really, really careful. So, you know, I think, and I think most people, you've been, I've heard you say before that you don't really need a lot more than 120 grams, most people, because you just can't burn like after 30, 40 grams at a meal. you're not getting much benefit. And you're just a burden on the kidneys. They've already had compromised kidney function. It's a challenge. So if you have to go, I think for most people, it's about 15% protein. And that level stays the same. The real challenge for everyone is to figure out the balance between carbs and fats. That's the key thing. Once you understand what your protein level, that doesn't change. You pretty much should have the same amount of protein continuously. The only other thing is to figure out what's the fat, what's the carbs. It's a central... argument or essential challenge for everyone to figure out. So for the protein, in fact, I think we have a pretty good idea. It's about one gram per kilogram of lean body mass. So it's not used to be, you know, every day, I think like 0.5, which I think is too low. But also one gram per kilogram of body weight turns out to be too much for some people too, because a lot of your tissue, which is fat tissue, is not metabolically active with the protein that you're ingesting. So it's really mostly for the lean muscle mass that you ingest in this protein. And for most people, let's say they're about 20% fat and another significant percentage bone. So you're about like 0.7 grams per kilogram of body weight is probably what you need to be striving for protein-wise. Now for fat, you know, basically the, I guess the level at which the fatty acid oxidation will compete with the glucose oxidation and kind of like shut it out is different for. different people and depends mostly on the endocrine balance. If you look at older people, they have the so-called, and sick people as well, they have metabolic inflexibility. So if you give them a meal that's comprised of equal number of calories of carbs and fats, they're going to oxidize most of the fats and the carbohydrates will go unmetabolized. So they will raise their blood glucose and also the lactic acid, which is the byproduct of unsuccessful of the fermentative carbohydrate utilization. So I guess you need to play with a ratio, but I've noticed that between 15% and 20% is probably where most people in their current health state are, at which they can metabolize the fat without causing problems through the rental cycle for the glucose. Diabetic people, especially type 2 diabetes, most of them are overweight. In fact, most of them are obese. which means they have a plenty of supply of fat. In fact, they have two sources of fat, of supplying fat, one through the diet and the second one through their, from their fatty tissue, basically because there's always some process of lipolysis going on, which means shredding the fatty tissue and supplying the rest of the body with the fatty acids from your fatty tissue. So they have two supplies, two sources of fat. So for diabetic people, it's probably a good idea to lower the intake of fat from the diet because they already have a lot. coming from their own bodies. In fact, there's many clinics around the world that treat and even cure type 2 diabetes by putting diabetics on this really restrictive diet until they lose most of their fat. And then suddenly the metabolism of glucose gets restarted. So I think this directly shows you that the problem with the glucose wasn't the glucose itself. It wasn't the glucose that was fattening them up and the glucose that's causing the problems, but they had too much fat in their bodies. Once you get rid of that fat, no matter how you do it, you can do it through. fasting. You can do it through uncoupling agents such as dinitrophenol, which raises your metabolic rate, right? Once you get rid of the fat, the problems with metabolizing glucose disappear. Which to me is a great test about the Randall cycle. So anyway, the question on the Randall cycle is, is it, is it the, is it the organism level, that percentage of fat concentration? Is it throughout the day? Is it through each meal? And is that cycle shifted in each mitochondria or is the cell level or the tissue level? So I would want to dive into some of the specifics of where is that control mechanism? And, you know, I think ideally you probably want it. Certainly the average for the day should be that, but should you also go to the effort of seeking to have that ratio of not more than 30% at each meal? So different tissues have different preference for the amount of fat versus the amount of glucose they burn. As I mentioned, the muscles at rest, but not during activity, prefer to burn predominantly fat. The brain prefers to burn predominantly glucose. And in fact, now they're saying that the reason the ketogenic diet is beneficial for things like epilepsy. it's because it has a glucose-sparing effect. There is something about the brain of epileptic people that don't utilize glucose as much. By the way, they do produce a lot of lactic acid as well, which means they're not metabolizing, which means they need a lot more of it. And by giving them a little bit of ketones, they can basically get by on a lesser amount of glucose. So the brain prefers to burn glucose. The reproductive system prefers to burn glucose. The gastrointestinal tract prefers to burn glucose. I think the liver... It's kind of like it can go both ways. You can actually produce, you can use lactate to convert back into glucose and then oxidize that. You can oxidize fat, right? But the different organs have different preferences. And I think the best way to kind of like to gauge whether you're eating too much fat is cognitive function. If you're eating too much fat to the point where you're basically, you know, interfering with glucose metabolism, you'll start getting the so-called brain fog. Your thinking process will slow. You'll start like basically, you know, spend more time searching for words. Your reaction time, coordination time will basically decrease. You'll kind of feel out of it, out of it a little bit. And that's actually notorious for people with type 2 diabetes and even type 1 diabetes. Their cognitive symptoms are overwhelming to the point that sometimes some of these people basically saying that there are certain days they cannot get out of the house because they feel like if they get in the car, they're going to crash it. Or if they go to a meeting, they can't even, you know. compose the normal set of words that they need to compose in order to actually get through the meeting. So brain fog is a great one. I think sleep quality is another great example of whether you're consuming the wrong ratio of macronutrients. Also exercise capacity. So if you're always catching your breath and you're feeling fatigued all the time, that is actually a great sign slash symptom of elevated lactic acid. And in fact, many different interventions that lower lactic acid are used as... performance-improving substances, vitamin B1 being one of the nice, cinnamite also being a great one. I'm going to talk about this later, I guess. So really, I guess the goal would be is to eat the fuel with each meal, probably different macroration nutrients depending on the time of the day. I would say eat the more fat-heavy meals earlier in the day, breakfast and maybe lunch, and then eat the more carb-heavy meals at night because your brain and many of the other organs will really need that. So it's very common. that if you don't consume sufficient amount of carbs before going to bed, you will have trouble sleeping. People in high-protein diet know that it's notorious, but they shouldn't be on the diet to start with. But people in a high-fat diet also have problem with sleeping. And I think one of the reasons is that if you don't consume sufficient amount of glucose, you will, of course, raise cortisol at night and elevated cortisol at night, which, by the way, it's already higher than what it should be. The cortisol is lowest at around 3 or 4 p.m., and it starts rising with the with the coming darkness. And his cortisol is highest at around 6 to 8 a.m. in the morning. So it keeps rising from about 4 to 5 p.m. on the previous day until 8 o'clock in the morning of the next day. But if you don't consume sufficient amount of carbs, that cortisol will be like that much higher, up to 40% higher. There was a study that measured the cortisol level of people on low-carb diets and found them to be not statistically significant different than people with Cushing syndrome. So basically people that do not eat sufficient amount of carbs at night before going to bed. And I think to me, that's probably the greatest example is that because sleep quality can determine so much more than just what are you going to feel the rest of the next day. People with sleep disturbances are known to have much higher rates of every chronic disease out there. Cancer, diabetes, Alzheimer's disease, Parkinson's disease. In fact, now they call it the shift worker disease. People that are now working these night shifts are suing various governments around the world and saying, These nice shifts are killing us. You need to pay us 10 times more because we need to compensate for this. But they are. That's well documented. That's well documented. And I think the reason is they basically work throughout the night when they should be resting. Their cortisol is higher when they're actually active because at least when you're asleep, cortisol doesn't have to maintain an additional activity, which if there's no fuel, the cortisol basically, you know, basically if you're awake during the night, the cortisol has to be that much more higher to shred your muscles and provide you with additional glucose. But even without the extra activity. If you're not consuming sufficient carbs at night, you will have problems sleeping and you will wake up feeling unrested and probably jittery the next morning because cortisol and adrenaline will be too high for comfort. Okay, well, you just walked into one of my three dozen or more questions I compiled since the last time I interviewed you, because I've been keeping track for this business interview. So there is a lot of evidence, Sachin Pandit being one of the primary researchers out of California at the Salk Institute, that suggests that there's great benefit to not eating three to four hours before you go to sleep. Essentially, enhance autophagy regeneration repair mechanisms. So I think there's probably still some value to that. But I just want to tease out the details with you because it would seem from my perspective that you don't want to eat a big meal before you go to bed. So but there's still this issue. And I think I violated this rule that I thought it was no calorie. But just from just what you said, it appears that there's some value in eating some clean carbohydrates. That's going to be the next question we discuss is what is a clean carbohydrate before you go to bed? So I'm wondering if you could talk about. any potential impairment for autophagy and regeneration response with respect to timing before bed? And what is the, I imagine a clean carbohydrate would be like honey or maple syrup or some, even some fruit, but what is the quantity and the timing before you go to bed? So a couple of things on autophagy. I know it's the hot thing right now, just like AMPK activation. I had a recent blog post about that, but AMPK and autophagy, and by the way, AMPK promotes autophagy. are actually implicated in cancer. You do not want to mess with autophagy too much. It has a lot of beneficial effects in terms of getting rid of dead or metabolically deranged tissue. However, if you do have an already present form tumor, autophagy and AMPK can actually drastically increase its aggressiveness and promote metastasis. Number one, so let's say you do want to increase autophagy. I think it's a bit of a myth that eating will somehow suppress autophagy. below and put it at a suboptimal level. I sent Dr. Saladino several studies demonstrating that actually several of the carbohydrates are autophagy enhancers. Fructose is, tracheolose, which is a fungal sugar, yes, it is. Sucrose is. Fructose, sucrose enhance, increase autophagy. Who would have known? Who would have known? Yeah, same to the link, similar to the link that I sent you. Chorizo increases inflammation. If you say this in the medical school, they'll probably throw you out. They'll say you're out of your mind. So what is the quantities and what do you find? I know it's a range. The timing, is it like right before bed? Is it an hour before bed? I would say an hour before bed because if you eat a meal that's too high in carbohydrates, basically you can get, there's the infamous fructose malabsorption. There's only a certain amount of carbohydrates that your gastrointestinal tract can absorb per unit of time. So you need about an hour or two before basically the meal, if it's composed of simple carbohydrates. God forbid you ate the resistant ones because then you... We'll talk about that next. Yeah. Then you've been about an hour to two hours for people with really slow digestion to get these things into your bloodstream. And then I think at that point, you'll probably be fairly relaxed at that point and you'll naturally be inclined to fall asleep. Now, if you're eating the resistant starch, then you're basically going to have this issue of endotoxin buildup. and you're going to have the so-called restless leg syndrome. For a long time, medicine has been mystified by this condition, but they've noticed that people who eat resistant starches have a higher incidence of restless leg syndrome. Why would that be? And then one scientist said, well, okay, so it's probably something to do with the bacteria because these people always complain of bad digestion at night. So they administer drugs that block either the TLR4 receptor, which is the endotoxin receptor, Or they gave them the dopamine agonist known as Pramipexol, which also turned out to be blocking many of endotoxin's effects. In both cases, the restless leg syndrome disappeared. So the issue with basically being jittery and not being able to relax at night has to do with two things. Either increased inflammation due to the increased endotoxin coming from your gastrointestinal tract. If you eat non-easily digestible foods and or. the subsequent elevation of cortisol, which is already high because it's at night, right? The cortisol has to keep you alive. Don't let blood sugar drop too low. So, but if you're eating a resistant starches, then you're going to raise cortisol even more. So you have high inflammation, a high cortisol going throughout the night. And I think most people who eat primarily resistant starches, especially the vegan types, if you go to the message boards on the internet, they're notorious for complaints of like, okay, I love this diet. I lost a lot of weight on it. but it's really destroying my sleep. What can I do about it? And so far, based on what I've seen in these message boards, nobody has really proposed any solution, simply because I guess it's kind of like not kosher to admit that eating certain type of carbs is going to mess up your digestion, which is fairly well established in the research circles. It's just not very widely publicized. Yeah. So this is another huge, massive, important concept that people need to understand because when they first, in the introduction, I mentioned that I'm eating about 60% of my diet is carbohydrates, but it's not just any carbohydrates. You have to be very, very specific and people think you can just throw them on there. And no, you can't. And especially when the Randall cycle is activated towards fat burning, because if you have, if you're, my experience clinically, and from what I read is that if you're fat. intake is over 40% and you throw these carbohydrates on there, you're going to disrupt your lipoprotein profiles. You're going to increase your risk for heart disease. You're going to shoot out triglycerides because you're not metabolizing the carbs and it's going to disrupt your lipoprotein. So you do not want to do that. The fat has got to be below 35%, somewhere in that range. But anyway, the carbs are not just for this restless leg syndrome at night. This is for the whole day. You want to eat the right types of carbs because this endotoxin is a huge... deal driving increased cortisol levels and inflammation in the body with the endotoxin and serotonin it's it's massively so you've got to so what we talk about this resistant starches so why don't you expand a little bit i have some questions about some of the healthy carbs that are either tip their brains or tubers like potatoes and rice that probably don't qualify it can be safe carbs but not quite as good as the ripe fruits just three days ago you basically mainstream media admitted that endotoxin drives obesity and diabetes. I thought I would never see this in a mainstream news media, but The Guardian and The New York Times and I think The Washington Post, because they were copying each other's articles, but they all came out and said, endotoxin is probably what's making you fat. It's not so much basically how much you exercise or the amount of calories in. If you're eating, which means really the calories in versus calories out, that article for me kind of did it, did it in. It said, okay. It's not so much about that. It's about what you eat, right? And how you metabolize it. So the resistant starches are starches that are basically resistant to hydrolysis, which mostly happens into the stomach and the small intestine, which means they arrive almost undigested to the colon where the massive microbiome, which outnumbers our cells in at least, I think 10 to one, something like that. There's like 10 copies of you in your colon. Then they say, oh, yummy, give me those resistant starches. And they have the necessary enzymes and the acids to actually hydrolyze them into simpler carbs that they can actually consume and digest. However, every time you eat a bacterial colony food, the turnover of the bacterial cells into that colony is going to increase. And all of the gram-negative bacteria, there's gram-positive and gram-negative, have this component in their wall called endotoxins. So all the bacteria die, they rupture, and they spill it out into your colon. That... That amount of endotoxin basically can attach to your intestinal wall and just the presence of endotoxin, just physical adsorption, AD, to the colonic wall can cause an inflammatory reaction which makes the cells of the colon produce a lot of nitric oxide and serotonin. Both of these are actually very inflammatory. Over time, if you keep producing this endotoxin and the colonic wall is chronically low-grade inflamed, you're going to compromise the gut barrier. And basically what's going to happen is some of the endotoxin will get into your bloodstream and it is known universally. Even if you pick up a mainstream doctor off the street, he'll tell you endotoxin in your bloodstream, major problem. We don't want that. We're using it, you know, to test for various, you know, immunosuppressive reactions, immunoactivating reactions. A lot of the adjuvants in the vaccines are actually acting like endotoxin. They're triggering an inflammatory reaction to wake up your immune system and say, oh, pathogen. Start producing antibodies against that pathogen. But it's known that chronically doing that, right, you don't get injected with a vaccine every day. And it's for a good reason. These adjuvants can actually wreak havoc. So they act the same way as endotoxin. And every time you're eating long chain carbohydrates that are not capable of hydrolysis in the stomach, but a gastric acid, which is mostly hydrochloric acid, then they reach the colon, the microbiome, and then, you know, they start feeding the bacteria there and causing a chronic inflammatory reaction. To make things worse, as your metabolic rate declines, the amount of gastric acid you produce also declines. And the gastric acid is the primary barrier for bacteria present in the food and in general surroundings, in basically the nose and the respiratory system, from actually going through your digestive system and starting to colonize the small intestine. Ideally, the small intestine and the stomach should be as close to sterile as possible. Now, you may have an H. pylori infection, which causes... ulcers and whatnot, but that's relatively rare and can be treated with antibiotics. It's not, the H. pylori does not really cause these metabolic disturbances that the regular, you know, bacteria that's in your colon that can cause. So once you start colonizing the small intestine, that compromises its digestive, its... nutrient-absorbent abilities. So with advancing age or declining metabolic rate or increased inflammation, you produce even less acid. So more of these carbohydrates that you ingest, even the simple ones may not even get properly digested and end up into the colon or even the small intestine now colonized by bacteria. And all of this process drives the chronic production of endotoxin every time you eat. So with each meal, whatever does not get digested and absorbed in the stomach and the upper third of the small intestine. becomes food for bacteria. And ultimately, that's a huge problem down the road for you health-wise. Yeah. So this is something we generally want to avoid. This is really one of the central tenets of your and Ray P's work is to avoid these for the most part. The amount of serotonin we need is really, really very low. The biggest role of serotonin is gastrointestinal motility. And for everything else, any increase, even minor increase of serotonin, It's been known since the 1920s to rapidly lead to fibrosis. The most successful antifibrotic drugs on the market currently are serotonin blockers, specifically the- We're going to go deep on that in a future podcast with you because that's a big rabbit hole we can dive down. Because so many people are taking drugs, and especially I think it's like 40% of women over 40 are on SSRIs. So this is a big issue for a lot of people. And I don't want to dismiss it and treat it superficially. So we'll go deeper on that. It's just another one. But- All right. Well, thanks so much, Charlie. Appreciate it. Thanks so much for watching. Remember, hit the like and subscribe button so you can get more videos that can help you and your family take control of your health.

He's just opened my eyes to so many foundational basics. We are gonna dive deep into the science. I think there is hardly a chronic condition where you cannot look at the condition and don't see cortisol implicated. And usually, in the majority of cases, it is elevated cortisol versus the low cortisol.

I think it's a very good argument that cortisol is catabolic to the brain. And clearly, if it's catabolic to the brain, it's probably not going to improve your mood. If anything, it's going to worsen it.

If you don't consume a sufficient amount of glucose, you will, of course, raise cortisol at night. It has been shown that cortisol levels... do not decline with age unless you really have adrenal failure, while the levels of all of these anti-cortisol youth-promoting hormones declines with aging.

Multiple intervention studies have demonstrated if you administer agents that oppose cortisol, block it at the receptor level, or reduce its synthesis, you can achieve really good health results and also the way you look. There's many clinics around the world that treat and even cure type 2 diabetes. by putting diabetics on this really restrictive diet until they lose most of their fat. And then suddenly the metabolism of glucose gets restarted. So I think this directly shows you that the problem with the glucose wasn't the glucose itself.

It wasn't the glucose that was fattening them up and the glucose that's causing the problems, but they had too much fat in their bodies. Once you get rid of that fat, no matter how you do it, the problems with metabolizing glucose disappear, which to me is a great test about the Rando cycle. who is just beyond amazing.

Thank you. Thanks for inviting me again. Hopefully the information we put out there is useful and people can improve their health.

So from our very first conversation, what literally blew my mind was the information you shared about cortisol. Of course, everyone knows about cortisol. We've certainly taught about it in medical school. And if you look it up, you'll see that cortisol... is responsible for glucose homeostasis is what they typically for regular glucose levels.

But they, you know, well, that's true. It really doesn't explain what it does. It's a rescue hormone and its primary function.

It's a glucocorticoid means it's the first part of it is glucose. That's what it does. It increases your glucose levels because if you go too low, you will go into hyperglycemic coma and you are dead. So it's, it's a rescue hormone and thank God it's available.

It's only secondary component is an anti-inflammatory. So what Georgie explained is that when your glucose levels drop, you have to do this and to shred your protein. It's just, it's a very highly anti-catabolic protein. And I was listening to one of your podcasts this morning, Georgie, where you explained that the primary benefit of anabolic steroids to build your muscle mass is that it's anti-cortisol.

That's how it works. It's like, oh, who would have known? You would have thought it had some direct action on the muscles directly, but no, it's anti-portisols, like mind blown again. This is another mind blowing that does this, but it's also the primary driver for aging.

It is the hormone responsible for accelerating your aging process. And one of the reasons I got into this, and most people are biohackers, is that they want to throttle that down. throttle it back so you're slowing the aging process yet virtually no one and i know almost every major leader and thought leader in this space and i've never really heard anyone talk about this this is this is like mind-blowing information so with all that massive introduction i don't think i've ever given a longer introduction before an interview to anyone but this is going to be a long interview so it's worth it just to frame it so why don't you comment on what i just said I mean, I fully agree.

I think there's hardly a chronic condition where you cannot look at the condition and don't see cortisol implicated. And usually, in the majority of cases, it is elevated cortisol versus the low cortisol. In fact, the only situation where you have low cortisol and it becomes problematic is probably Addison's disease, which is truly adrenal failure. And that's rare, very, very rare.

In fact, the only high-profile person that I know that had it was President Kennedy, John F. Kennedy. And he took for life, I think he took cortisol injections every couple of days. But for everybody else, now, if you look at John F. Kennedy, even with those injections, he basically was in a state of relative cortisol deficiency.

But if you look at him, he looks remarkably young and handsome. Not that he was very old when he became president and killed, but he looks younger than what other people at this age look like. And especially people at this age that are, if you look at them these days, they're going to look on average a lot older than JFK. And studies as far back as the 1950s and 60s demonstrated that you can produce every single phenotype of aging if you inject cortisol or at least create a state of relative glucocorticoid excess in the animal.

So you can do that either by injecting synthetic or natural glucocorticoids, or you can do it by reducing the levels of the natural anti-cortisol steroids in the body. And those are pregnenolone. progesterone, DHEA, but in males, testosterone, and also dihydrotestosterone.

So if you reduce the levels of those anti-cortisol steroids and keep the cortisol levels normal as they are in the animal, you will still achieve the same kind of like the phenotype of aging. And that's actually pretty much what happens to people as well. It has been shown that cortisol levels do not decline with age unless you really have adrenal failure, while the levels of all of these anti-cortisol youth-promoting hormones... declines with aging. Prenatalone, DHEA, progesterone, by the time you're 80, their levels are at about 20% of what they used to be when you were in your 20s.

So really what happens is that cortisol stays the same, but basically your relative state of cortisol increases because there's nothing to oppose the cortisol that is already there. And multiple intervention studies have demonstrated if you administer agents that oppose cortisol, block it at the receptor level, or reduce its synthesis. you can achieve really good, you know, both health results and also the way you look.

The anabolic steroids are probably the best known example. It's really a misnomer because they're not anabolic. They're actually anti-catabolic. Muscle has one of the highest expressions of the glucocorticoid receptor through which cortisol shreds the muscle.

It binds the receptor. It increases a number of different proteolytic enzymes. I just got to know muscle is the highest.

It is? Really? And gastrointestinal tract and brain.

So these are the three places where the receptor is the best. So cortisol actually shreds your brain tissue too? Exactly. And it causes massive brain atrophy. And it's been well established for the last five decades that cortisol can actually cause depression.

People with depression have smaller brain mass and brain volume than people that don't have depression. This was probably one of the most convincing arguments to classify depression as actually as a... physiological condition in addition to being purely mental as well.

They looked at MRI scans of people with depression. They saw they have, depending on how severe the depression is and for how long it went untreated, these people had much smaller brain volume and a number of brain cells as well, number of neurons. So they said, okay, can we form the hypothesis that maybe cortisol can cause depression if it's chronically elevated? Let's test it. Let's administer an anti- cortisol medication to animals and people and see what happens.

Within 48 hours of the glucocorticoid blocker, RU486 being administered to people with clinical treatment-resistant depression, they experience remission. So I think it's a very good argument that cortisol is catabolic to the brain. And clearly, if it's catabolic to the brain, it's probably not going to improve your mood. If anything, it's going to worsen it. Well, thank you for that.

And I think, so ultimately... As I mentioned, when your blood sugar level drops, that's a trigger for you to increase cortisol. This is the last thing you want to do.

Really, one of your primary goals in achieving optimal health is to literally limit the elevation of your cortisol, much more dangerous than sugar level elevation, which almost everyone is focusing on. They've got monitors, the 24-7 glucose monitors, continuous glucose monitors called CGMs. that you can wear, and pretty much every five to 10 minutes, you're going to get a reading, because they're so concerned how dangerous glucose is. But that's not the issue.

The issue is cortisol. Yep. And fats, right?

So if your blood glucose is rising... They're connected. That's what we're going to talk about. They're connected. So instead of asking, okay, is elevated blood glucose a symptom or a cause of the pathology?

So far, we've only been told that, hey, high blood glucose is the devil. You got to have everything in your power to lower it. However, all of the drugs on the market, especially the more recent ones that actually target lowering HbA1c, the glycated hemoglobin, all of them increase all-cause mortality.

So clearly, messing directly with the levels of blood glucose, it's not something you want to do. You may temporarily decrease the biomarker, the glycated hemoglobin, but it does not mean you're getting healthier. There was a famous Harvard medical professor who said that the moment a biomarker becomes a goal, it's easiest to become, it's easiest to be a biomarker.

So you're starting to chase something that's just a symptom. And unfortunately, for many conditions, simply because medicine says that they don't know what the cause is, then you're kind of relegating yourself to symptomatic treatment. And that's really what most of these blood glucose lowering drugs do.

They may lower your blood glucose, but they may kill you in the long run faster than the elevated blood would have done by itself. I just want to make it clear that we are not saying that it is not important if your blood glucose is elevated, but it's a symptom. It is not the, you don't want to hit that directly.

You want to address the fundamental foundational cause and then everything else comes into place. And just to give you an example, when on my first interview with you, I was still relatively high fat, 70, 80% fat. Now I realize that wasn't a serious chapter. Fortunately, I could tolerate it.

I didn't have too many bad side effects, but it wasn't optimizing my health. Now I am down to like 27% fat and like 57, 58% carbohydrates. And so having said that, you say, oh my gosh, you must be diabetic.

So no, I lost five pounds more. I really was a healthy body weight. And my blood sugar, I just hadn't been done.

It went down. My fasting blood sugar went down 10. So. You know, it's not, that's just to me, personal anecdotal proof that it's not the carbohydrate ingestion.

It's that what's happening at the mitochondrial level. And to help us understand that I created a graphic because this science can get somewhat complex when, when Georgie describes it. And I just thought having a simple graphic.

Now you can look at this, it looks complicated, but when we discuss it, it will be okay. So basically it shows that you only have two primary fuels that you can burn in your body, food, and that's fats and carbs. And the fats are broken down from a process called beta-oxidation and ultimately wind up going to acetyl-CoA, which gets fed into the Krebs cycle.

Now, carbs are different chemical structures. So they are a six-carbon molecule. And when they're broken down, they break down to pyruvate. And this is really important because pyruvate then can also turn into acetyl-CoA, but it has to be enzymatically changed through an enzyme called pyruvate dehydrogenase, PDH, or some people call it PDC, pyruvate dehydrogenase complex.

So when this complex or the enzyme itself is inhibited, we've got major problems because glucose can, you know, the substrate pyruvate cannot go into the electron-sense point of change. And instead it has to go backwards, not really backwards, but to another pathway, a primitive pathway. pathway, one of all the central single cell organisms and bacteria and such. And that is glycolysis, where it essentially anaerobically ferments that fuel to create energy.

And it's very inefficient. It doesn't create a lot of ATPs. And the lactate molecule itself, when produced in large quantities systemically as a result of glucose being shunted, will cause wreck havoc with your system. Your body has a metabolic switch.

In many ways, a switch is a switch very similar to the one on a railroad track, where the train comes along and then you throw the switch and it goes down a different track. It can only go down one track at a time. You can't do, the train can't split itself in two and go down both tracks. So there's a switch. And actually, this switch has a name.

It's called the Randall cycle. It essentially describes a process where your tissue can only burn one fuel at a time. It can't burn fat and glucose at the same time.

And glucose is the same as a synonym for sugar. So the threshold appears to be, and this is different for different people, but it's about 30%. And what do I mean? If your fat level is above 30%, and you're not going to be able to take that sugar, that glucose, and run it through your mitochondria, which is a small organelle within almost every blood. in cell in your body, except for the red blood cells, that produces cellular energy in the form of ATP.

That's really one of the primary differences between higher order organisms and lower order ones like bacteria. They don't have mitochondria, we do. And it's very efficient at creating energy. However, if your fat content, the percentage of fat that you're consuming in your diet is over 30%, then this sugar is backed up and it can't go through the mitochondria. It has an alternate source.

That alternate source is called glycolysis and essentially is very inefficient. You can take one molecule of glucose and you only make two, two ATP. That's it.

And it also doesn't require oxygen. And then so we think, well, that's great. It's not going to create many reactive oxygen synthesis, which is actually quite to the contrary, because it's so inefficient, it's going to create a lot more. reactive oxygen species. And we'll talk about that in a moment.

So if your fat level is under 30%, And in some cases where there's some pretty severe metabolic inflexibility, like obesity or diabetes, that level may have to decrease to 15 to 20%, which is pretty extreme. That's a pretty low-fat diet. I don't think it ever really should go under 10%, but the lower you can go, the better that you can tolerate. Usually diets under 10% fat are going to be very hard to tolerate. It's just not doable for most people.

But if you... the threshold appears to be 30%. If you have less than 30% of your total calories as fat, then the glucose that you're ingesting can be used efficiently in your mitochondria.

And we'll talk, there's some different ways that you can burn that even within the mitochondria if your fat is less than 30%. And we'll talk about that in a moment. But that's the primary principle is you got to get the fat level right first, first and foremost.

And then you can hope that you're going to have a chance of burning this. The ideal ratio is not really known, but the epidemiological studies kind of show that about an equal percentage in terms of calories is probably optimal for long-term health, unless you're trying to tackle a specific... Equal of fats and carbs?

No, no. I'm saying 33%, 33%, 33% for a healthy person. No, here's where I would respectfully, very respectfully disagree, because...

And that's in the whole of the discussion is the protein. I've got so many insights from you, but most people don't get it now. but you can get too much. So like in my case, you know, I have some kidney challenges because of mercury fillings that I had removed incorrectly 30, over 30 years ago.

And as a result, I have to be really, really, really careful. So, you know, I think, and I think most people, you've been, I've heard you say before that you don't really need a lot more than 120 grams, most people, because you just can't burn like after 30, 40 grams at a meal. you're not getting much benefit.

And you're just a burden on the kidneys. They've already had compromised kidney function. It's a challenge.

So if you have to go, I think for most people, it's about 15% protein. And that level stays the same. The real challenge for everyone is to figure out the balance between carbs and fats.

That's the key thing. Once you understand what your protein level, that doesn't change. You pretty much should have the same amount of protein continuously.

The only other thing is to figure out what's the fat, what's the carbs. It's a central... argument or essential challenge for everyone to figure out. So for the protein, in fact, I think we have a pretty good idea. It's about one gram per kilogram of lean body mass.

So it's not used to be, you know, every day, I think like 0.5, which I think is too low. But also one gram per kilogram of body weight turns out to be too much for some people too, because a lot of your tissue, which is fat tissue, is not metabolically active with the protein that you're ingesting. So it's really mostly for the lean muscle mass that you ingest in this protein. And for most people, let's say they're about 20% fat and another significant percentage bone. So you're about like 0.7 grams per kilogram of body weight is probably what you need to be striving for protein-wise.

Now for fat, you know, basically the, I guess the level at which the fatty acid oxidation will compete with the glucose oxidation and kind of like shut it out is different for. different people and depends mostly on the endocrine balance. If you look at older people, they have the so-called, and sick people as well, they have metabolic inflexibility.

So if you give them a meal that's comprised of equal number of calories of carbs and fats, they're going to oxidize most of the fats and the carbohydrates will go unmetabolized. So they will raise their blood glucose and also the lactic acid, which is the byproduct of unsuccessful of the fermentative carbohydrate utilization. So I guess you need to play with a ratio, but I've noticed that between 15% and 20% is probably where most people in their current health state are, at which they can metabolize the fat without causing problems through the rental cycle for the glucose. Diabetic people, especially type 2 diabetes, most of them are overweight.

In fact, most of them are obese. which means they have a plenty of supply of fat. In fact, they have two sources of fat, of supplying fat, one through the diet and the second one through their, from their fatty tissue, basically because there's always some process of lipolysis going on, which means shredding the fatty tissue and supplying the rest of the body with the fatty acids from your fatty tissue.

So they have two supplies, two sources of fat. So for diabetic people, it's probably a good idea to lower the intake of fat from the diet because they already have a lot. coming from their own bodies.

In fact, there's many clinics around the world that treat and even cure type 2 diabetes by putting diabetics on this really restrictive diet until they lose most of their fat. And then suddenly the metabolism of glucose gets restarted. So I think this directly shows you that the problem with the glucose wasn't the glucose itself.

It wasn't the glucose that was fattening them up and the glucose that's causing the problems, but they had too much fat in their bodies. Once you get rid of that fat, no matter how you do it, you can do it through. fasting. You can do it through uncoupling agents such as dinitrophenol, which raises your metabolic rate, right? Once you get rid of the fat, the problems with metabolizing glucose disappear.

Which to me is a great test about the Randall cycle. So anyway, the question on the Randall cycle is, is it, is it the, is it the organism level, that percentage of fat concentration? Is it throughout the day? Is it through each meal?

And is that cycle shifted in each mitochondria or is the cell level or the tissue level? So I would want to dive into some of the specifics of where is that control mechanism? And, you know, I think ideally you probably want it. Certainly the average for the day should be that, but should you also go to the effort of seeking to have that ratio of not more than 30% at each meal?

So different tissues have different preference for the amount of fat versus the amount of glucose they burn. As I mentioned, the muscles at rest, but not during activity, prefer to burn predominantly fat. The brain prefers to burn predominantly glucose. And in fact, now they're saying that the reason the ketogenic diet is beneficial for things like epilepsy. it's because it has a glucose-sparing effect.

There is something about the brain of epileptic people that don't utilize glucose as much. By the way, they do produce a lot of lactic acid as well, which means they're not metabolizing, which means they need a lot more of it. And by giving them a little bit of ketones, they can basically get by on a lesser amount of glucose.

So the brain prefers to burn glucose. The reproductive system prefers to burn glucose. The gastrointestinal tract prefers to burn glucose. I think the liver...

It's kind of like it can go both ways. You can actually produce, you can use lactate to convert back into glucose and then oxidize that. You can oxidize fat, right?

But the different organs have different preferences. And I think the best way to kind of like to gauge whether you're eating too much fat is cognitive function. If you're eating too much fat to the point where you're basically, you know, interfering with glucose metabolism, you'll start getting the so-called brain fog. Your thinking process will slow.

You'll start like basically, you know, spend more time searching for words. Your reaction time, coordination time will basically decrease. You'll kind of feel out of it, out of it a little bit.

And that's actually notorious for people with type 2 diabetes and even type 1 diabetes. Their cognitive symptoms are overwhelming to the point that sometimes some of these people basically saying that there are certain days they cannot get out of the house because they feel like if they get in the car, they're going to crash it. Or if they go to a meeting, they can't even, you know. compose the normal set of words that they need to compose in order to actually get through the meeting. So brain fog is a great one.

I think sleep quality is another great example of whether you're consuming the wrong ratio of macronutrients. Also exercise capacity. So if you're always catching your breath and you're feeling fatigued all the time, that is actually a great sign slash symptom of elevated lactic acid. And in fact, many different interventions that lower lactic acid are used as...

performance-improving substances, vitamin B1 being one of the nice, cinnamite also being a great one. I'm going to talk about this later, I guess. So really, I guess the goal would be is to eat the fuel with each meal, probably different macroration nutrients depending on the time of the day.

I would say eat the more fat-heavy meals earlier in the day, breakfast and maybe lunch, and then eat the more carb-heavy meals at night because your brain and many of the other organs will really need that. So it's very common. that if you don't consume sufficient amount of carbs before going to bed, you will have trouble sleeping. People in high-protein diet know that it's notorious, but they shouldn't be on the diet to start with. But people in a high-fat diet also have problem with sleeping.

And I think one of the reasons is that if you don't consume sufficient amount of glucose, you will, of course, raise cortisol at night and elevated cortisol at night, which, by the way, it's already higher than what it should be. The cortisol is lowest at around 3 or 4 p.m., and it starts rising with the with the coming darkness. And his cortisol is highest at around 6 to 8 a.m.

in the morning. So it keeps rising from about 4 to 5 p.m. on the previous day until 8 o'clock in the morning of the next day. But if you don't consume sufficient amount of carbs, that cortisol will be like that much higher, up to 40% higher.

There was a study that measured the cortisol level of people on low-carb diets and found them to be not statistically significant different than people with Cushing syndrome. So basically people that do not eat sufficient amount of carbs at night before going to bed. And I think to me, that's probably the greatest example is that because sleep quality can determine so much more than just what are you going to feel the rest of the next day.

People with sleep disturbances are known to have much higher rates of every chronic disease out there. Cancer, diabetes, Alzheimer's disease, Parkinson's disease. In fact, now they call it the shift worker disease. People that are now working these night shifts are suing various governments around the world and saying, These nice shifts are killing us. You need to pay us 10 times more because we need to compensate for this.

But they are. That's well documented. That's well documented.

And I think the reason is they basically work throughout the night when they should be resting. Their cortisol is higher when they're actually active because at least when you're asleep, cortisol doesn't have to maintain an additional activity, which if there's no fuel, the cortisol basically, you know, basically if you're awake during the night, the cortisol has to be that much more higher to shred your muscles and provide you with additional glucose. But even without the extra activity.

If you're not consuming sufficient carbs at night, you will have problems sleeping and you will wake up feeling unrested and probably jittery the next morning because cortisol and adrenaline will be too high for comfort. Okay, well, you just walked into one of my three dozen or more questions I compiled since the last time I interviewed you, because I've been keeping track for this business interview. So there is a lot of evidence, Sachin Pandit being one of the primary researchers out of California at the Salk Institute, that suggests that there's great benefit to not eating three to four hours before you go to sleep. Essentially, enhance autophagy regeneration repair mechanisms.

So I think there's probably still some value to that. But I just want to tease out the details with you because it would seem from my perspective that you don't want to eat a big meal before you go to bed. So but there's still this issue. And I think I violated this rule that I thought it was no calorie. But just from just what you said, it appears that there's some value in eating some clean carbohydrates.

That's going to be the next question we discuss is what is a clean carbohydrate before you go to bed? So I'm wondering if you could talk about. any potential impairment for autophagy and regeneration response with respect to timing before bed? And what is the, I imagine a clean carbohydrate would be like honey or maple syrup or some, even some fruit, but what is the quantity and the timing before you go to bed?

So a couple of things on autophagy. I know it's the hot thing right now, just like AMPK activation. I had a recent blog post about that, but AMPK and autophagy, and by the way, AMPK promotes autophagy.

are actually implicated in cancer. You do not want to mess with autophagy too much. It has a lot of beneficial effects in terms of getting rid of dead or metabolically deranged tissue. However, if you do have an already present form tumor, autophagy and AMPK can actually drastically increase its aggressiveness and promote metastasis.

Number one, so let's say you do want to increase autophagy. I think it's a bit of a myth that eating will somehow suppress autophagy. below and put it at a suboptimal level.

I sent Dr. Saladino several studies demonstrating that actually several of the carbohydrates are autophagy enhancers. Fructose is, tracheolose, which is a fungal sugar, yes, it is. Sucrose is. Fructose, sucrose enhance, increase autophagy.

Who would have known? Who would have known? Yeah, same to the link, similar to the link that I sent you. Chorizo increases inflammation. If you say this in the medical school, they'll probably throw you out.

They'll say you're out of your mind. So what is the quantities and what do you find? I know it's a range. The timing, is it like right before bed? Is it an hour before bed?

I would say an hour before bed because if you eat a meal that's too high in carbohydrates, basically you can get, there's the infamous fructose malabsorption. There's only a certain amount of carbohydrates that your gastrointestinal tract can absorb per unit of time. So you need about an hour or two before basically the meal, if it's composed of simple carbohydrates. God forbid you ate the resistant ones because then you...

We'll talk about that next. Yeah. Then you've been about an hour to two hours for people with really slow digestion to get these things into your bloodstream. And then I think at that point, you'll probably be fairly relaxed at that point and you'll naturally be inclined to fall asleep.

Now, if you're eating the resistant starch, then you're basically going to have this issue of endotoxin buildup. and you're going to have the so-called restless leg syndrome. For a long time, medicine has been mystified by this condition, but they've noticed that people who eat resistant starches have a higher incidence of restless leg syndrome.

Why would that be? And then one scientist said, well, okay, so it's probably something to do with the bacteria because these people always complain of bad digestion at night. So they administer drugs that block either the TLR4 receptor, which is the endotoxin receptor, Or they gave them the dopamine agonist known as Pramipexol, which also turned out to be blocking many of endotoxin's effects.

In both cases, the restless leg syndrome disappeared. So the issue with basically being jittery and not being able to relax at night has to do with two things. Either increased inflammation due to the increased endotoxin coming from your gastrointestinal tract. If you eat non-easily digestible foods and or. the subsequent elevation of cortisol, which is already high because it's at night, right?

The cortisol has to keep you alive. Don't let blood sugar drop too low. So, but if you're eating a resistant starches, then you're going to raise cortisol even more.

So you have high inflammation, a high cortisol going throughout the night. And I think most people who eat primarily resistant starches, especially the vegan types, if you go to the message boards on the internet, they're notorious for complaints of like, okay, I love this diet. I lost a lot of weight on it.

but it's really destroying my sleep. What can I do about it? And so far, based on what I've seen in these message boards, nobody has really proposed any solution, simply because I guess it's kind of like not kosher to admit that eating certain type of carbs is going to mess up your digestion, which is fairly well established in the research circles.

It's just not very widely publicized. Yeah. So this is another huge, massive, important concept that people need to understand because when they first, in the introduction, I mentioned that I'm eating about 60% of my diet is carbohydrates, but it's not just any carbohydrates.

You have to be very, very specific and people think you can just throw them on there. And no, you can't. And especially when the Randall cycle is activated towards fat burning, because if you have, if you're, my experience clinically, and from what I read is that if you're fat. intake is over 40% and you throw these carbohydrates on there, you're going to disrupt your lipoprotein profiles.

You're going to increase your risk for heart disease. You're going to shoot out triglycerides because you're not metabolizing the carbs and it's going to disrupt your lipoprotein. So you do not want to do that. The fat has got to be below 35%, somewhere in that range.

But anyway, the carbs are not just for this restless leg syndrome at night. This is for the whole day. You want to eat the right types of carbs because this endotoxin is a huge... deal driving increased cortisol levels and inflammation in the body with the endotoxin and serotonin it's it's massively so you've got to so what we talk about this resistant starches so why don't you expand a little bit i have some questions about some of the healthy carbs that are either tip their brains or tubers like potatoes and rice that probably don't qualify it can be safe carbs but not quite as good as the ripe fruits just three days ago you basically mainstream media admitted that endotoxin drives obesity and diabetes. I thought I would never see this in a mainstream news media, but The Guardian and The New York Times and I think The Washington Post, because they were copying each other's articles, but they all came out and said, endotoxin is probably what's making you fat.

It's not so much basically how much you exercise or the amount of calories in. If you're eating, which means really the calories in versus calories out, that article for me kind of did it, did it in. It said, okay. It's not so much about that. It's about what you eat, right?

And how you metabolize it. So the resistant starches are starches that are basically resistant to hydrolysis, which mostly happens into the stomach and the small intestine, which means they arrive almost undigested to the colon where the massive microbiome, which outnumbers our cells in at least, I think 10 to one, something like that. There's like 10 copies of you in your colon. Then they say, oh, yummy, give me those resistant starches.

And they have the necessary enzymes and the acids to actually hydrolyze them into simpler carbs that they can actually consume and digest. However, every time you eat a bacterial colony food, the turnover of the bacterial cells into that colony is going to increase. And all of the gram-negative bacteria, there's gram-positive and gram-negative, have this component in their wall called endotoxins. So all the bacteria die, they rupture, and they spill it out into your colon. That...

That amount of endotoxin basically can attach to your intestinal wall and just the presence of endotoxin, just physical adsorption, AD, to the colonic wall can cause an inflammatory reaction which makes the cells of the colon produce a lot of nitric oxide and serotonin. Both of these are actually very inflammatory. Over time, if you keep producing this endotoxin and the colonic wall is chronically low-grade inflamed, you're going to compromise the gut barrier.

And basically what's going to happen is some of the endotoxin will get into your bloodstream and it is known universally. Even if you pick up a mainstream doctor off the street, he'll tell you endotoxin in your bloodstream, major problem. We don't want that.

We're using it, you know, to test for various, you know, immunosuppressive reactions, immunoactivating reactions. A lot of the adjuvants in the vaccines are actually acting like endotoxin. They're triggering an inflammatory reaction to wake up your immune system and say, oh, pathogen. Start producing antibodies against that pathogen. But it's known that chronically doing that, right, you don't get injected with a vaccine every day.

And it's for a good reason. These adjuvants can actually wreak havoc. So they act the same way as endotoxin.

And every time you're eating long chain carbohydrates that are not capable of hydrolysis in the stomach, but a gastric acid, which is mostly hydrochloric acid, then they reach the colon, the microbiome, and then, you know, they start feeding the bacteria there and causing a chronic inflammatory reaction. To make things worse, as your metabolic rate declines, the amount of gastric acid you produce also declines. And the gastric acid is the primary barrier for bacteria present in the food and in general surroundings, in basically the nose and the respiratory system, from actually going through your digestive system and starting to colonize the small intestine.

Ideally, the small intestine and the stomach should be as close to sterile as possible. Now, you may have an H. pylori infection, which causes...

ulcers and whatnot, but that's relatively rare and can be treated with antibiotics. It's not, the H. pylori does not really cause these metabolic disturbances that the regular, you know, bacteria that's in your colon that can cause.

So once you start colonizing the small intestine, that compromises its digestive, its... nutrient-absorbent abilities. So with advancing age or declining metabolic rate or increased inflammation, you produce even less acid. So more of these carbohydrates that you ingest, even the simple ones may not even get properly digested and end up into the colon or even the small intestine now colonized by bacteria.

And all of this process drives the chronic production of endotoxin every time you eat. So with each meal, whatever does not get digested and absorbed in the stomach and the upper third of the small intestine. becomes food for bacteria.

And ultimately, that's a huge problem down the road for you health-wise. Yeah. So this is something we generally want to avoid. This is really one of the central tenets of your and Ray P's work is to avoid these for the most part. The amount of serotonin we need is really, really very low.

The biggest role of serotonin is gastrointestinal motility. And for everything else, any increase, even minor increase of serotonin, It's been known since the 1920s to rapidly lead to fibrosis. The most successful antifibrotic drugs on the market currently are serotonin blockers, specifically the- We're going to go deep on that in a future podcast with you because that's a big rabbit hole we can dive down.

Because so many people are taking drugs, and especially I think it's like 40% of women over 40 are on SSRIs. So this is a big issue for a lot of people. And I don't want to dismiss it and treat it superficially.

So we'll go deeper on that. It's just another one. But- All right.

Well, thanks so much, Charlie. Appreciate it. Thanks so much for watching.

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Transcript for:Cortisol's Impact on Health and Diet

Transcript for:
Cortisol's Impact on Health and Diet