Scientist Reveals the Truth About Carbs — and Why They’re Making You Sick! | Dr. Andrew Koutnik

I was a fat kid growing up. I had obesity as a kid. I failed for over half a decade on all these various diet strategies. And I eventually found success with reliably and sustainably changing my diet.

All these things that happen to people, who cares if it's unfair? You can use it as a tool on your journey to improve your health and use it to empower yourself.

When people think, well, what should the healthy person do? Well, that's an odd question to ask nowadays because that's actually the exception. Nine out of ten Americans have some type of metabolic dysfunction. Nine out of ten of them would have either an elevation in blood glucose levels, adverse changes in elevation in lipids like triglycerides, or one of these other biological biomarkers that we know are associated with health that are going in the wrong direction.

I hope the sports nutrition industry will pay attention to this. These heavy amounts of carbohydrates that are being pushed onto athletes is not for free. "Lionel Sanders," a world champion Ironman competitor, he went on to develop, following the sports nutrition guidelines, super lean, exercising sometimes four-plus hours per day, pre-diabetes. Went to the doctor, got his blood work back. Everything looked good except for his glucose levels were going into the pre-diabetes range.

I'm gonna give you the three free tips anyone could have to try to improve their health. No one's making money off this. This is just what works. Number one "Andrew," when it comes to the keto diet, who would you say it's right for and who would you say it's not?

I think the first thing we should talk about is what it's not good for. I think that's a term that we typically use in medical science or work called contraindications. And so contraindications are examples of what you would not use something for where it could be dangerous. So a ketogenic diet requires the ability to utilize fat that you consume in your own fat stores. And one of the key contraindications, while it is extremely rare, is genetic alterations to fat metabolism. So things where you're no longer able to metabolize certain parts of the fat in various tissues. This would make it very, very difficult to utilize the primary fuel source on the ketogenic diet in the form of fat. Those are incredibly rare though.

And so then it gets to something called what we call as relative contraindications. So things that we thought at one point might have been something you shouldn't use the ketogenic diet for, but there really wasn't solid evidence to suggest that was universally true, or maybe that was true at all. It was just hypothetical. And one was actually the type 1 diabetes, which is a disease that I have, which now that has completely flipped on its head. We now know that the ketogenic diet is a very evidence-based strategy for the management of glucose and insulin and other key biomarkers in diseases like type 1 diabetes. And so there remain a number of relative contraindications, but many of those are starting to be addressed by research. And we're finding out that there might be more applications for things like the ketogenic diet than we thought before. But in short, the main reason someone should not do a ketogenic diet is if they actually cannot metabolize fat appropriately. And that's usually due to some type of genetic alteration that is incredibly rare.

Now, what could it be for? Which is the opposite question, what could this actually be utilized for? Well, for essentially 200 years, or actually technically over 200 years, it's been used for managing and reversing diabetes. So we know back to 1796, the original report, or one of the original reports at least that I'm aware of, that actually showed the ability to utilize this diet in patients with type 2 diabetes. We know with standard of care in type 1 diabetes as well. Prior to discovery of insulin, we knew it was used for neurological disorders such as seizures. Since 1921, we've also had an emergence of evidence in other conditions with some emergent evidence in randomized controlled trials looking at things like early-onset cognitive decline or Alzheimer's. With some randomized controlled trials looking at ketogenic diet's ability to assist with - providing resilience against cognitive decline, we've also seen the emergence of what are observational and case reports in psychiatric conditions such as depression, schizophrenia, and bipolar. Now that it's a very emergent field, the evidence is not such that it's reached the point of massive mounds of randomized control trials. But there was a meta-analysis that came out in "JAMA Psychiatry" that actually showed that across 50 different studies and 10 randomized controlled trials - in depression, it has been shown to actually reduce depression in individuals. So it seems like it's quite a powerful approach for a large number of conditions.

The one I didn't mention that's the most common amongst those in the developed world and unfortunately growing in other parts of the world is obesity. So we know that the development of excess adipose tissue on your body, obviously driven largely by excess caloric intake, reduced physical activity, ultimately can lead to an abundance of excess adipose tissue on the body. And we have known since 1860s that the ketogenic diet can be utilized for that as well.

But really, this is really just a diet that has a couple key components to it. Number one, it's a diet that largely focuses on whole foods. - So you're removing a lot of the processed, refined foods that make it incredibly difficult to sustain normal body weight, keep hunger under control, which is one of the key drivers why people find themselves over-consuming and gaining excess weight. Excess weight is really one of the key drivers of a lot of the metabolic problems we see in the developed world. That's one key component. We also know that the reduction of carbohydrates in and of itself helps remove the likelihood of being exposed to foods that I was describing, these ultra-processed foods, the refined carbohydrates. It also is a pretty simplified approach. If you're just reducing carbohydrates, a lot of people are pretty familiar with what those are. And so just removing them makes it pretty, not completely, but largely makes it quite simple for people to understand how to do this. And people tend to find a lot of success with this approach. There's a lot of momentum because they tend to lose... weight rather quickly. And that doesn't mean it's fat weight necessarily, by the way. It means that there's water weight drops for a number of reasons we can get into if you're interested. But there's also the inherent volitional reduction in caloric intake for many individuals because they're removing so many of the foods that was driving hunger in the first place for them.

Ketogenic diet's not the only diet that works for many of these things, by the way. It's just one of the most effective evidence-based strategies that have been around for centuries because of its simplistic approach and another way of saying it's a lethal simplicity, a very potent strategy and one of the many powerful tools in the toolbox.

I think it's important early on in the conversation we zoom in on weight gain... and obesity... and talk about what happens there classically. And then we'll flip into keto. And when somebody switches their metabolism, how they can walk their way out of it.

Sure. So when someone, let's say they're in their younger years, they have never had a problem with weight before. Although that's becoming actually not uncommon to see people developing obesity in childhood. Actually, I was... someone who did about two decades ago... But when someone starts to consume more calories than their body is expending, their body begins to... store the excess nutrients they're not burning on their own body. So you start to store that predominantly in fat, because fat is the one area of the body where you can store excess tissue almost... in theory, to no upper limit. - You've all heard of examples of individuals up towards of 400, 500-plus pounds, and that 400, 500-plus pounds is not muscle, obviously. That's overwhelmingly fat. And that fat is being stored in excess because our body is extremely good at doing that. And it's extremely good at doing that because of our history. Our history as a species went through feast and famine. And when we went through famine, we needed excess storage of nutrients when we couldn't get food. And the best way to store that was in the form of fat. Well, unfortunately, our culture has evolved at such a rapid rate where our genetics have not caught up with that same evolutionary rate. And as a result, our bodies are prepared to constantly store nutrients in anticipation of famine that we never experience anymore. We're constantly over-consuming and our body is constantly placing that excess abundance of calories on our body and storing it predominantly as fat.

Now, when someone gains excess fat beyond, let's say, a normal healthy level on the body, that's when we start to see early changes of things like insulin. This is one of the first things that changes. So insulin starts to elevate when people get into and creep into levels of obesity, usually around doubling and up to typically... insulin will double, sometimes... quadruple, when people go from normal body weight to getting into a classification of obesity. Now, it's not just insulin though. We also know that there's excess amounts of amino acids and lipids that are now floating around the blood. So a lot of people call type 2 diabetes energy toxicity, which is the extreme end of this. But it's true. You're seeing an abundance of not just glucose that drives insulin higher, but also amino acids, also lipids. And there's also some other changes in things like inflammatory signals and oxidative stress signals. And so pretty early on, in the early onset of obesity, we see elevated insulin, early signs of insulin resistance, around a 33 to 36% reduction in insulin sensitivity in the muscle and whole body. And then as people progress further and further into obesity, before they even see elevations in blood glucose levels, insulin levels can go up sixfold. Their insulin resistance can go up to 75 to 80% in the muscle and whole body tissues and all these other biomarkers we're describing the amino acids, the lipids, inflammation, oxidative stress signals, they're also rising as well. And so we're seeing this composite change with obesity just because of the excess adipose tissue that is being stored in the body. And... it is at that point where, when multiple years of that persist, that the body can no longer maintain that level of excess homeostasis. And as a result, the blood sugar levels begin to rise. So this is when we start to see the incidence of something called prediabetes, where blood glucose levels can no longer be maintained in the normal range anymore. And as a result, they start to rise. But they only start to rise after years of these changes happening under the surface. And that's really the consequence of obesity. It isn't just a superficial thing when you look in the mirror or how people look at you. It's actually something that's happening under your skin, in your cells and in your blood.

Well, let's take it down to the cells and talk about changes there. How much of this growth or putting on tissue, in this case fat tissue, are cells getting bigger versus multiplying? And then let's talk about different fat deposits in different areas of the body, whether it be visceral fat, liver fat. We've been talking about it in a general sense, but let's really break it down.

So, great question. So actually, we'll take that in reverse order and talk about where the fat gets deposited. So initially, when people start to begin to gain weight, they start to begin to gain weight in these peripheral tissues like the leg and other regions. But there becomes a point where people start to gain excess amounts of weight in the general, central region of the body. Now, people may wonder, why does that matter? Well, that's something called visceral fat. And visceral fat has been associated with many health consequences, but it's the deposition of fat in the central part of the body which has been linked to many health consequences. But it's also linked to insulin resistance and a number of biological changes that is pushing your metabolism in the wrong direction.

Now, when it comes to the other question you pose, which is, what's happening with these cells or these fat cells? Well, there. There was a prevailing theory, obviously the fat cells are enlarging. So there's something called lipohypertrophy, or the hypertrophy means growth or growth in size. People think of hypertrophy typically in the context of muscle, but it also applies to fat as well. And lipo means fat. So fat growth and these grow. But there's also a prevailing belief that these cells grow to a point that and then they separate, divide into individual new adipocytes and then those grow. So you're actually growing not only the size, but also the number. - And then as people start to go into a deficit, there's also a belief that now you have more fat cells lingering around. And as a result, as more fat cells shrink, more counter-regulatory hormones are released to trigger your brain to think you're in a state of starvation. And that state of starvation triggers your brain to want to feed more. So this is where the biological mechanisms arise that say, hold on, we had all this excess adipose tissue and now it's all shrinking. We don't want that. And generally speaking, from an evolutionary perspective, we would not want that. But we don't live in the same state that our body evolved in. We live in a place of abundance where very few people ever go into a state of famine for more than 24 hours without food. And as a result, your body's constantly in a state of abundance. And this is where you find individuals gaining a ton of weight, and then you also find them struggling once they gain that weight to bring it off. This is why it's obviously, they say, an ounce of prevention is where the count, a pound of cure. - This is the case not just in scenarios like smoking is the best example, where if you stop smoking in the first place, you can prevent so many other problems down the road. Same thing with obesity. It tends to be much easier if you can prevent its onset in the first place than try to reverse it once it's initiated. But unfortunately...

90%. So there's two statistics here. There's one at Tufts University at 88% and "UNC," University of North Carolina, Chapel Hill, at 93%, showing that around basically nine out of ten Americans have some type of metabolic dysfunction or biomarkers shifting in the wrong direction. Meaning that if we were to go to United States of America, look around in a room, we have 10 adults in the room, nine out of 10 of them on the average would have either an elevated waistline, an elevation in blood glucose levels, adverse changes in elevation in lipids like triglycerides, or one of these other biological biomarkers that we know are associated with health that are going in the wrong direction. And that's almost every adult in the United States. So we know this isn't an uncommon thing. When people think, well, what should the healthy person do? Well, that's an odd question to ask nowadays because that's actually the exception. It's not. That's definitely the exception, not the rule. And so a lot of what we talk about nowadays is what is, what can we do to improve the health of the entire nation, which most people contend are largely sick or on their way to being developing some type of chronic metabolic condition.

I want to zoom back a couple of minutes and highlight something you brought up there. The fact that our fat has a memory and will pull us back towards wanting to gain weight if we've been at a weight for a certain period of time. Talk more about the nuance there. How long do we have to be overweight to have that physiological effect? And then for somebody that applies what we're talking about today, brings the weight down, gets metabolically healthy, does their metabolism and new balance of their body weight ever reset?

That's a great question. So what you're referring to is like a metabolic set point. So this idea of this, are you shifting the point at which your body feels normal or at... a neutral place? And I'm going to be honest with you, I don't know if we know that answer today. I don't know if we know the answer by which every individual person, as they progress through, why we see individual differences between some individuals who are very predisposed to not only gaining weight but not able to reverse that weight. Because we've always met that one person who could consume an abundance of calories and never worry about this, and then there's other people who look at food, the joke is they just look at food and they gain weight. So there's these huge biological differences of which we don't totally, completely understand why that is the case, although we do know that there are some key metabolic changes. For example, there's a hormone called leptin that got a lot of appreciation over the years because that's one of those hormones that actually, as the adipose tissue shrinks, is released and triggers hunger in the brain. In fact, we actually did studies when I was working with a clinical physiologist who actually looked at leptin and actually found some rare genetic disorders of leptin deficiency. And these individuals would be hungry all the time, meaning --- they were no longer able to produce leptin within the body, and as a result, they were never feeling satisfied. And as a result, then they administered a drug called metreleptin. This is a very expensive drug. I'm pretty sure it's not largely approved, but when it was administered, they lost an abundance of weight, a huge amount of weight. But this is a very rare thing that occurs. But it's an illustration of unique hormonal metabolism, or hormone-induced changes in hunger signaling where things like leptin, as a response to shrinkage of adipose tissue, can drive hunger. But it's not the only molecule that does this. We know that typically when fat cells shrink, there's also shrinking because insulin's also lower. Well, when insulin's lower, that sets off a cascade of changes within the body. Arguably, I would contend that insulin is the most powerful hormone in all metabolism. And when it goes high, it causes changes in virtually every major tissue in the body, and when it comes low, it does the same thing, and actually tends to regulate other tissues or other hormones like glucagon. And so as insulin goes higher, we know that it stores fat. As it goes lower, it frees up the ability for fat to be broken down and utilized as a fuel source. And so there's quite a lot of things that are happening. But the exact reason why someone would get to a set stage and then find it difficult once they lose weight, or what their set point is, let me get to that. That was something that was being proposed. Well, I actually don't know the original date it was proposed. I know there were theories being proposed upwards of over a decade ago as to why that was the case, but I'm not sure that we have the exact answer to that, unfortunately, today.

Okay, so to kind of summarize where we're at with all this. Over time, we're taking in too many carbs, too much sugar, insulin's ramping up to deal with blood glucose. A lot of times that'll be masked because the insulin is rising and keeping the blood glucose in check. So people are only measuring the blood glucose, they may be missing what we're talking about here. Let's talk about from an insulin and glucose perspective. The glucose would be later, after metabolism breaks. That would be down the line when somebody is in that type 2 diabetic range. But let's start with insulin, then get to blood glucose and talk about problems that arise in the body. Again, starting with insulin, things like cancer, damage to blood vessels. We've been focusing on obesity, but there's all kinds of other problems under the hood.

Sure. So, to back up for a second, when we were talking about things like excess sugar and carbohydrates, that's certainly one of the key drivers. But there are many ways that people can obviously gain weight. -- - But yes, that's one of the most common reasons, the excess consumption of these types of refined, sugary carbohydrates in the diet. - But as someone gets further along in that stage and they start to consume more of these foods, when sugar rises and you consume it, actually, let's back up for a second and take your audience through it. So let's say that someone were to consume rice or bread or a potato... what happens?

Okay, well, let's say you consume that food. Say you went and got Chinese food, who knows? And there's a bunch of rice and maybe some sushi or something like that. And you consume it. It goes to the stomach, your stomach starts to break it down, and it takes the rice and starts to break it down from these chains of glucose called polysaccharides because saccharides are sugar molecules to the individual glucose molecules. And then it's absorbed. And once it's absorbed... so the more you consume, the more sugar that's going to be absorbed. - And the more sugar that's absorbed, the more that those sugar molecules cause an elevation in blood glucose. Well, that elevation in blood glucose causes this very unique but yet powerful tissue called the pancreas to sense the elevation in glucose and work like a thermostat as glucose rises. The higher it rises, the more it's going to generate and release insulin rapidly into the bloodstream. Okay, rapidly because... an abundance and elevation in glucose signals the body, okay, we're in a... in a state of abundance. We need to now store this tissue, at least first in the liver. Also block fat breakdown because we want to keep that fat because now we're in an abundant state. And now, if we have excess spillover, we may put some more in the muscle. And as a result, it's... it's signaling all these growth and signals in the body. Once that happens, blood glucose comes back down. Then you go through this state of not -- consuming over time. However, your question is what happens when insulin, I assume what you're getting at, is in abundance... over time, in excess amounts?

Well, we know that insulin has a pretty powerful effect on various tissues. Excess amounts of insulin within the body, in and of itself, can cause insulin resistance, let's say at the peripheral tissues. One of the most common peripheral tissues... is the muscle. The muscle is the largest sink of glucose in the body, what we call the large glucose pool. You have the small glucose pool and a large glucose pool. We can explain that more if your audience is interested, but the large glucose pool is the muscle. This is where you can store, at least in an average body weight female, somewhere around 300 to 350 grams of... glucose and stored glycogen. And in males, 500 if you're very well trained, maybe north of that. - So 500 grams of glucose. We're talking about 2,000 calories worth of glucose just sitting in your muscle. --- When insulin is in excess at that tissue, in those tissues... what happens in type 2 diabetes, actually, is when it's in excess over time, you start to develop resistance towards that insulin. So at the cellular level, there's internal signals that allow for, when insulin binds to that muscle, to cause a cascade of internal signals that allows for glucose to be brought into the cell. Well, when excess amounts of insulin is exposed to that muscular tissue, it actually develops resistance. So internal signals within the muscle start to change. You start to develop... dysfunctions to the signals within the cellular tissue. And as a result, insulin doesn't work as well. Okay, that's one of the ways in which it occurs. But there are other ways in which insulin resistance may manifest. But... another area of the body that is key, beyond the muscle, is the brain. We know that insulin has a direct effect in key areas of the brain. - And so when we think about something like when someone goes during a lunch this may not be you, but someone may be listening who this may be the case for where let's say they had lunch... They --- woke up and they took their kids to school, they go to work, they've been at work for four or five hours. They say, okay, it's lunchtime, thank God. Let me leave and go get some food, enjoy my life for like an hour, if they're lucky. And then they go and eat like a sandwich. So they eat a sandwich. That sandwich probably has 60 to 80 grams of carbohydrates in it. They consume the sandwich, they feel great for 30 minutes. Then about an hour to an hour and a half, two hours later, they start to feel pretty... fatigued. All of a sudden, they're starting to feel that post lunch lull. They feel like they need to take a nap. Well, that is all... in part the rise in blood glucose levels, but a huge component of that... is the insulin effect on the brain. - And insulin's effect on the brain can cause some of these effects and alongside glucose changes like fatigue. So we know that insulin could also affect that, but we also know that insulin is associated with water uptake and water retention in various tissues. This is why excess amounts of insulin is associated with high blood pressure. And the reduction of insulin within the body, or reduction of insulin resistance within the body, is often associated with a resolution, in many cases, of hypertension or high blood pressure. And really, the list goes on and on and on. And this is why so many people talk about insulin resistance as one of the root causes of many... of the chronic diseases that we are seeing in excess amounts today. It's certainly not the only cause. I'm not going to sit here and say that it is, but it's... often... apparent in many of the major conditions... we see and rising levels within the developed world. Obesity is clearly one of them. - But there's other conditions that we know are also linked to this. We talked about high blood pressure, cardiovascular disease. -There's clearly a link there as well. We know that excess insulin is the hallmark physiologic change in type 2 diabetes called insulin resistance. I could go on and on and on and on and on, but we know that insulin resistance is at least... common and prevalent in many... of the major chronic diseases rising today. And if it's not the direct cause in the case of type 2 diabetes, it certainly is... argued to be one of the causal drivers. - And I say argued to be. There's many causes. Many different causes for each person. But in other conditions, maybe it's a passive bystander. Not a passive bystander, but an active bystander, adding gasoline onto the fire of other conditions, let's say mental health conditions, where these changes in things like glucose and insulin are challenging the brain's ability to stay in a normal metabolic state, a neurobiological state. And this could place some individuals who are at higher risk for maybe... rapid fluctuations or dysregulation within the brain. Which is interesting because we see this emergence of the ability, as individuals start to normalize glucose levels, normalize reduce and normalize insulin levels. So we're not having the high and variable insulin or glucose levels that individuals start to see improvements in some mental health conditions. Again, those data are very preliminary, I must acknowledge, but... it's very interesting nonetheless to see that linkage, knowing that there's a clear... neurological... impact of something like insulin in the body. So insulin's a very, very powerful hormone. It's the master regulator. It affects various tissues, we mostly think of it as a fat storage hormone, but it has a lot of other effects within the body. But really we're not concerned about it. It's essential to life, but in excess is where the problems arise.

You gave a couple examples there, somebody having rice, somebody having a sandwich. How different is that response in the body... with insulin and blood glucose, somebody metabolically healthy versus somebody metabolically deranged?

So... one of the first major changes we see is this change in beta-cell response. So when individuals start to develop things like prediabetes, or they start moving further and further along in insulin resistance and develop prediabetes, we see actually changes in the ability to actually have the first- and second-phase insulin response. So right as blood sugars rapidly start to elevate, you have this rapid initial response of insulin. Well, in individuals who start to develop prediabetes and we've seen this in individuals with obesity who have prediabetes they lose a lot of that initial first insulin response. As a result, their second insulin response is delayed, which means they have an initial higher peak in blood glucose than someone who is healthy. But then because it's delayed, they have a... delayed reduction in blood glucose after the food has already been absorbed and resolved from the bloodstream. And now you can get into incidents of a postprandial, or what they say post-food-intake, hypoglycemia. So that's really one of the initial changes that occurs is actually occurring at the beta cell, or where the insulin is actually produced, at the first-phase insulin response. But as you start progressing further and further, it can get so far down the road in the case of type 2 diabetes where the beta cells themselves begin to be damaged and not able to produce as much insulin at all. So not only are you not able to have insulin do its job when it is produced, but now you're not able to produce as much. And this is really what happens at the kind of extreme tail end... or further end of type 2 diabetes where individuals are very far along in the disease process. And insulin's not just the inability to function, but it's the inability to even produce enough of it. And now that's a very, very, very dangerous situation down the road of that disease.

Is that reversible when somebody gets to that point?

So I'm going to answer that by describing it... from before someone gets type 2 diabetes... So we've conducted randomized controlled trials in individuals who were... some of them developed pre-diabetes. And what we see is that individuals who are... more healthy than not who have pre-diabetes if they're able to make rapid changes in their diet, particularly the reduction in carbohydrates in their diet low enough to reduce glucose and insulin levels, they see a rapid, within days resolution of their pre-diabetes. It just disappears. - Now, we see individuals who aren't as healthy who develop pre-diabetes. It can take more time, and oftentimes, the individuals who have pre-diabetes who may have excess adipose tissue, -- not just a reduction in things like carbohydrates, but a reduction in body weight, sustained elevation in physical activity, because that keeps insulin more sensitive to really resolve that issue...

As you start pushing further and further along... from pre-diabetes to type 2 diabetes—the earlier on in the process, the easier it is to reverse. Why? Because you don't have a lot of the damage to various tissues and dysfunction that arise with... chronic elevations in glucose, insulin. But all the other things we spoke about the excess amino acids, the excess lipids, the excess inflammation, oxidative stress. And particularly those molecules, the inflammatory molecules and oxidative stress molecules are what are actually going to go to tissues and actually cause damage. - There are other causal effects of things like glucose in excess levels that directly damage tissues, by the way, like the vascular tissue, the brain tissue, et cetera... But... when insulin is in excess. When someone's pushing further and further along, they're starting to accumulate this damage. Which is why when we look at individuals who have developed type 2 diabetes and have lived with it for multiple years it's often believed that it's just a manageable disease, you're just managing this disease. Even examples where they put individuals on very low carbohydrate ketogenic diets and got them to lose weight. In the case of these big studies by "Virta," which is a company that puts individuals on very low carbohydrate-based diets, they have been able to reverse a large number of patients, but a lot of them are not. And if all those patients had pre-diabetes, you would expect them all if they had lost weight and changed their diet to resolve their pre-diabetes. But in the case of type 2 diabetes, we're not seeing that. And that is largely attributed to the damage that occurs over time. - And because in type 2 diabetes, -- oftentimes to reverse type 2 diabetes or put it into remission, whatever you want to call it, everyone's got their word they want to use. It also requires weight loss, sustained weight loss. In fact, one of the key drivers that someone reverses their type 2 diabetes is weight loss... And so... you have to lose weight too. And that is incredibly difficult for people to do in the first place. But two, sustain it. In fact, there's been statistics that have been around for quite some time that if someone tries to lose 20% of their body weight, which, by the way, a lot of people with type 2 diabetes need to do that, less than 5% of people will lose it and maintain it for at least a year. Well, if you have type 2 diabetes and you have 20% of body weight to lose, not only do you need to lose it, but you need to maintain that weight loss for the rest of your life. So if less than 5% of people are doing that at least up to a statistic about five, 10 years ago, then it's going to be incredibly challenging. And that's one of the biggest challenges, is that it also develops not just a shift in diet, but also a sustained commitment to a lifestyle that's going to allow you to sustain weight loss, which obviously has been a major challenge across the world.

You mentioned these people that went to "Virta" and weren't able to reverse their metabolic dysfunction. Are they able at this point to determine that up-front? Is there certain signs and symptoms that'll alert them to who these people are?

- I don't actually know the exact answer to that, to be totally honest with you. I would suspect that there's a number of factors that go beyond just why if someone, there's a sustainability factor as well here. - So when someone is recommended to go on a very low carbohydrate diet and do the exercise, are all the people doing it the same way? Are all the people adhering to the protocol the same way? Are all the people exercising as much as they should? And everyone requires a different degree of lifestyle change to induce these type of effects. So if that's the case, is everyone doing what they have to do, to the magnitude they need to do it, to cause those effects and sustain them? I bet the answer, a lot of that is just due to the inability for everyone to achieve the same outcomes by just adhering to the protocol to the same degree. Because this isn't necessarily an easy thing. We know that ketogenic diets, amongst all dietary changes, is maybe one of the few diets that by default has a ton of evidence that shows that people volitionally reduce their caloric intake. That's probably one of the few reasons that it's incredibly powerful and effective for that situation of weight loss because if it didn't resolve hunger, it is going to be incredibly difficult for it ever to be successful for sustaining weight loss for individuals... But in that case, I don't know the exact answer to that. I suspect a lot of it just has to do with the person's ability to actually sustain the lifestyle. Because I would put a lot of my money, and probably your money too. I'd take your money too. I'd take my money and your money and we'll put it into a pot and say, if those individuals fast safely for an extended period of time, I would bet that many of them will resolve their diabetes if they fasted long enough. But that's an extreme intervention that's not sustainable over time. You can't go without food forever. - But it goes to show if you push them to the extreme, then they probably would all resolve their type 2 diabetes at least for the time that they're in that state. So, I suspect a lot of it is just, are you able to put someone in a sustainable place that allows them to push their glucose and insulin biomarkers into an ideal range for long enough to get them to resolve their disease state? And if not, maybe they had to push further, and pushing further is not a sustainable thing for some of those individuals.

Do we know somebody who has pushed really far and they get to that point you talked about where the beta cells are being affected, destroyed, and insulin's actually decreasing because it can't produce it in the pancreas, is that ever reversible?

To my understanding, once tissues begin to die similar to Alzheimer's, very far progressive stage of Alzheimer's, when you actually start to see neurological or brain tissues dying, it's commonly believed that that is not reversible. ---- Which means that you would be... in the case of type 2 diabetes, where the beta cells are being destroyed. There is data that shows there are stem cells that you can restore various tissues within the body. -- All that is known to be true, but I don't think it has much application here. When someone has true death to various tissues, you often don't see a massive restoration of those tissues. There's a percentage of individuals that are more likely to restore some of that than others, but that's a small percentage. -- And so, it's largely believed to not be the case. So, if someone were to be able to reverse their type 2 diabetes when they're at that stage, it's almost certainly because the remaining amount of tissues present are able to assist them sufficiently with the dietary change to resolve glucose and insulin levels, or resolve glucose levels with a limited amount of insulin they're able to produce into a normal range. And actually, a great example of this is something called pancreatitis. So, when there's actually damage to the actual pancreas, like true damage to the pancreas where people lose complete functions of portions of their pancreas, you often don't see a massive resolution after the disease is present. - Like after disease is present, but after the event occurs, they've got permanent damage to the parts of the body that produce insulin, at least portions of it. And so, in large part, when those people develop that which is actually called type 3C diabetes is one where you actually develop a form of diabetes in response to pancreatitis. A lot of people say that like diabetes or Alzheimer's is type 3 diabetes in the brain. Well, there actually is a real type of type 3 diabetes, -- and there's actually like nine different types. And they're actually usually end result to damage the pancreas, like a pancreatitis. And it's largely believed that that's largely not reversible. But there are examples, although rare, of people doing very impressive revolutions to their health, their lifestyle, and seeing the ability to reverse some of these events. But it's usually the exception, not the rule.

Well, let's help people not get to that end of the spectrum by giving them early signs and symptoms. Obviously weight gain. You mentioned hypoglycemia. That would be a little bit more subtle, hard to detect. But what are the things early on people can look for and realize they're heading down this path we've been talking about?

Well, luckily, it's what you said, it's looking in the mirror. You can pretty quickly tell when you are. Most individuals are fully aware that they're gaining weight because they see themselves every day. They put on clothes that may not fit the way it used to. You look in the mirror, you don't look the way you used to. You're putting on excess body fat. A lot of people have scales in their home. They're seeing the scale rise. Those are the clear, easy signs. - Everything we're talking about after this is usually because that was let to persist for too long or not just persist, but actually get worse. And so, that's one of the early signs. But there are a number of biomarkers someone could assess early on to say, okay, even maybe I don't have excess adipose tissue, but am I metabolically healthy? And one of the big ones we talked about is insulin. - You can get a fasted insulin level to see if your insulin level is rising because one of the early signs, prior to elevations in glucose, is elevating insulin levels. So, a fasted insulin is probably not a bad idea. Although you want to make sure when you get that assessed that you control what you're eating the night before, because it can affect it. But just assuming you keep all these things controlled and you go get fasted blood work, your insulin levels are elevated that would start to indicate to you, okay, yeah, I'm gaining weight, my insulin's higher. - I'm starting to develop some degree of insulin resistance. If this continues, I'm in trouble. Because then what would happen? Well, when insulin starts to rise, we also see an elevation in things like triglycerides. Triglyceride elevation is not causal in things like heart disease, but it is a sign of underlying metabolic damage. - And so, you can test triglycerides. If they're elevated, that would be very concerning, particularly when looking at things like it's one of the many biomarkers related to metabolic syndrome. - Then you can also look at, obviously, fasting glucose levels, or an "HbA1c," which is a measure of your glucose levels over two to three months, or the emergence of continuous glucose monitors, which you can go test not just your fasting levels, but your response to meals and how each meal is affecting your blood glucose levels. That can be an incredibly informative process for individuals because there have been people who've reached out to me and said, hey, my doctor says I'm totally fine, but I slapped on one of these "CGMs," and now my blood sugar level goes to up to like 200 and 250 after meals. And by the way, I had pancreatitis two years ago. And I said, well, did they test you for type 3c diabetes? -- And did they test your C-peptide, which is a measure of how much insulin you produce? They said, oh, yeah, I did. My C-peptide is actually low. I was like, well, what number is it? And I was like, that number's diagnostic for diabetes. And so a lot of times, these are clues. But you have to advocate more often than not for these clues to understand what's going on. So we talked about weight. You can look in the mirror, you can see that change. You can also see it change on the scale. We talked about insulin because that's one of the first changes that occurs. And when that occurs, you start to see changes in triglycerides. Eventually you'll see an elevation in blood glucose levels. - And those are really the major early signs that things are starting to change in an adverse direction. But when that starts to change, when you have an elevation in body weight, when you start to see an elevation in triglycerides, an elevation in blood glucose levels those are actionable and changeable biomarkers, and you can do something about that when they elevate. So these aren't just biomarkers you can look at and say, oh, no, that's not good. Those are biomarkers that you can assess and actually manipulate immediately. And when we talked about things like continuous glucose monitors, those are things where you can manipulate what you're doing in real time, meal to meal, and actually see the differences. And I think that while just slapping a "CGM" on someone, a continuous glucose monitor by itself isn't necessarily going to induce a lifestyle change, although it has a minor effect, but it's not really meaningful, it can be incredibly empowering information for individuals to understand how they are responding to specific foods, specific lifestyle habits, and beyond. - I live with a disease called type 1 diabetes where we have had continuous glucose monitors for over a decade. It's actually how people without diabetes got them. It came from our disease, it was developed for us, and they were eventually given to other people. But we also can monitor insulin every single day. And the changes in glucose, they follow insulin levels. And you can just monitor this all the time to see, okay, I exercised today. I need about 10 to 20% less insulin all day. I go for a walk for one mile, and all of a sudden, I don't need nearly as much insulin today as I did the day before. These are incredible little insights into essentially gamifying your own health. But this also teaches you how things like exercise, things like various foods, will affect your biomarkers. And having that type of insight can be incredibly empowering if you use it to be empowered. Otherwise, it's just a bunch of junk information that's overwhelming and you do nothing with. But if you have the right intentions with it and you really use it as an actionable tool, they're very powerful.

Do you worry if somebody does get a "CGM" or tests "HbA1c" and they're in that early phase, relating back to everything we've been talking about where insulin's slowly rising, that a lot of the challenges could be masked, and they might give themselves that check that all is good and continue on the path they are? How do you see that concern?

If people start to see elevations in their fasting glucose levels, if they're seeing elevations in their "HbA1c," if they're seeing that their average glucose level on a "CGM" not only is elevated beyond normal levels, but are seeing high levels of variability that exceed what you would expect, then yes, you should do something yesterday. Because we know that in many of these conditions, particularly the best examples

are in diabetes, that there is... something called metabolic memory, that as glucose levels elevate and rise over time, that we start to see damage to tissues that are cumulative in response to how high they are, and it's not completely reversible. So the best day to figure it out is today. The best day to act is the second you find out you should act.

It's the best day. It's not tomorrow, the best day is today. Always. Every single time. And it isn't about revolutionizing your entire life, by the way, that's almost destined to fail. It's about just taking a single... step. Maybe you've heard, oh, wow, I heard on the podcast with "Jesse." I heard he said something about -exercise and the ketogenic diet. I don't exercise that much, but I might be able to reduce my carb intake. Awesome. Cool. Do that. Or maybe it's like, okay, well, I have a hard time reducing these diet factors, but I could go for a walk every morning. Awesome. Go do that. Just start. Because before you know it, you're walking one mile, you're walking two miles, you're walking three miles. You're starting to feel different. You're feeling more motivated, you feel more empowered. You feel like, maybe I don't need to have that food anymore because you know what, I just walked... three miles and I didn't used to do that anymore. So I can do hard things. And so you start to do other hard things, and before you know it you might be on the front of a cover magazine, or maybe "Jesse" will interview you on his next podcast. You never know what could come.

And I'm a lived example of that. I was a fat kid growing up. I had obesity as a kid. I failed for over half a decade on all these various diet strategies, these exercise protocols. My father was a marathon runner, my uncle had run 20 marathons, climbed mountains, done... century rides. I was around exercise my whole life, but I had a poor diet. I rode bikes every day, I played football, I did all these things. I got obesity. And I eventually found success... with reliably and sustainably changing my diet. And once I did that, I realized, oh my gosh, I feel so much better. My confidence is better... I can think better. And this was even in childhood. And I carried that for the rest of my life. And it became a career. Heck, it allowed me to do something that I felt was... meaningful and important. Now, I did get type 1 diabetes along the way, by the way, but that just changed it to a whole 'nother level. That just made me realize that my entire life was a scientific experiment that I could learn from. All these things that happen to people, it's not, who cares if it's unfair? It doesn't matter. You can use it as a tool on your journey to improve your health and use it to empower yourself. All these examples. I don't want to go any further. Go look on "YouTube." I'm sure you've interviewed tons of amazing people... who've been through something really powerful in their life, and it revolutionized their experience. And all of a sudden, now they're sharing their story with other people, and now they're empowering people. The people listening to your podcast, they could be that person... They just don't know it yet. The only thing they need to do is take the first step. That's what they need to do. They don't need to fix everything in their life, they're not going to. You're not going to be "LeBron James" tomorrow, you're not going to be "Lance Armstrong" tomorrow, but you might in 10 years, you might in 20 years. You never know.

So, again, it's just about taking the first step. Just as a quick side pivot as you share your story there. You mentioned being obese, getting type 1 diabetes. Do you feel like there's a connection there? That's a funny question because I think the last time we spoke, I would have said no. The answer to that is probably now yes. So as a researcher, you come across new data and information that makes you change the way you think, or at least hopefully changes the way you think when you're presented with new information. And I used to think type 1 diabetes, getting type 1 had nothing to do with lifestyle. Had nothing to do with the choices I made and the decisions I made, and as a result, it's not my fault. However, when you actually look at various reasons why someone gets type 1 diabetes, genetics doesn't explain it for the vast majority of people... It may increase your risk... for some people subtly. I have type 1 diabetes, my son's risk is 1 in 7 or 1 in 14. - Whereas "Jesse," if you don't have type 1 diabetes, or I assume you don't, if you had a son, his risk would be 1 in 300. Whereas mine is infinitely higher. But it's still very low. It's still less than a 10% chance.

But... when you start looking at things that... induce risk, and they look at this through these large epidemiological data sets where they look at people who have type 1 diabetes... and various factors that they had that would potentially link risk to developing disease. So let's say you had 100 people, they all had type 1 diabetes, and some people were overweight and some people weren't, some people had... got breastfed, some people didn't, some people had exercise, some didn't. And you can link what is the percentage of individuals or association between their onset of disease and one of those lifestyle... choices or habits or other factors. And so they looked at this for a number of different things. And one of the strongest... risks, reliably, not just for type 1 diabetes but for virtually every autoimmune disorder, is obesity. Obesity is one of the most powerful risk factors for developing type 1 diabetes. And I would have normally said in the past, honestly up to about two years ago, that obesity had nothing to do with my disease. In fact, I had lost a bunch of weight a year prior, but I did a whole hell of a lot in a five-year period with obesity. And as a result, I probably did put myself at dramatically higher risk for type 1 diabetes. In fact, I don't think I did, I know I did. Now, I don't know if it was the cause, but I don't know. No one knows what the cause is of their type 1 diabetes for the most part. Maybe you got a virus right before, maybe that was or wasn't the cause. Who knows? But we know that obesity dramatically increases the risk, just like we know certain viral infections increase the risk, and et cetera, et cetera.

I actually would say that the answer to that is almost certainly... it certainly added gasoline to the fire, and maybe it was the cause. And I don't ask that to point fingers towards type 1 diabetes, in your case, or anybody else with a chronic disease. But just to understand the physiology and give people a heads-up who are on that path that there's these other things that could be smoldering behind the scenes and certain consequences of living that lifestyle. Absolutely. And by the way, a lot of people do get offended when you talk about lifestyle factors causing type 1 diabetes. Probably largely because they've been told that it wasn't their fault. But the reality is that, yeah, there are a lot of things and choices that we're starting to realize that people are making that are putting them at risk. And yeah, type 1 diabetes isn't fair. Not everyone who's obese is gonna get type 1 diabetes, but it's dramatically increasing your risk. So let's just call a spade a spade. People need to have the accurate and right information. Obesity increases your risk. Obesity is something you can correct with lifestyle, period. So if you have obesity, it is potentially putting you at risk for getting one of these conditions. But it's also putting you at risk for diabetes. It's putting you at risk for cardiovascular disease. It's putting you at risk for neurological changes or at least, or at least early-onset adverse changes. There's so many things that it puts you at risk for. And arguably that's the most common universal theme among so many diseases, which is why the emergence of these new drugs like "GLP-1" receptor agonists, which reduce hunger in the diet so people can lose weight, are reducing virtually every major chronic condition in the United States when people take them. Because obesity is such a central driver of many of these adverse effects.

Now that we're into the "GLP-1" agonists, expand upon your thoughts in that realm. I think they're incredibly powerful tools. So when we think about people doing it, we've known that diet can help obesity for 200 years. Well, technically a little over 150 years, 170 years, actually. But still, people struggle with it. And so these are incredibly powerful tools that can help curb one of the most difficult parts of losing weight, which is the hunger. So if you're able to silence some of that hunger, it can help people make the right decisions they know they should make, but their brain and biology is telling them not to. And so that's what those tools are largely doing. Yes, there's some other peripheral effects, but the large overwhelming power of these drugs is to reduce hunger in the brain. And when they help reduce hunger, they allow people to make better choices with their food or -- let me say this differently. You would hope it would allow them to make better choices with their food, but what it's doing is just reducing the desire to eat. But what people should be aware of is that they need to be developing sustainable lifestyle strategies that allow them to shift towards better eating habits. Prioritizing the right type of food, which isn't always easy on these drugs because a lot of times on these drugs people want to have sugary and sweeter, sweeter-based foods. They just want a lot less of them. But the reality is that when you're in these massive caloric deficits these drugs induce, you need essential nutrients. That means protein and fat. And also a diet mostly composed of protein and fat will also help preserve things like muscle mass, which is something that some people are concerned about with these drugs and how rapid the weight loss is. - Although the data is kind of questionable if you're going to have that much muscle loss compared to just a diet-induced muscle loss. But either way.

The same theme is there are assistants and tools along the way. But you have to build sustainable lifestyle strategies. So I hope people would view these as tools in the toolbox to assist them in making the choices that are fundamental to overall health. Number one, choosing the right whole-foods dietary strategy that helps them feel good, maintain normal body weight, and remove themselves, if possible, of things that are conditions that they've developed. And we talked about the ketogenic diet, that's just one of the many choices that someone can make. Maybe one of the most evidence-based ways or diets that someone can make. But that's something that people need to develop along their journey. They also should be exercising. - "GLP-1s" don't necessarily make someone motivated to exercise, but they may help them lose weight so that every step they're taking around the block to walk that one mile... is not as heavy. -- Or maybe it helps them lose weight so they don't feel self-conscious walking into the gym for the first time, whatever it may be, they should be exercising as well, and realize that you're not alone. So anytime that you feel self-conscious of yourself and you're uncertain, I was that person, too. I was terrified to walk into the gym for the first time. No, but that's because I was terrified of what everyone's going to think of me. No one cared what I looked like. The only person who cared was myself. No one else cared. In fact, I can tell you as... someone who's been through this journey, when I see someone who is much heavier walking into the gym for the first time and getting after it. It's the most motivational thing. The most motivational thing. In fact, I was competing in a jiu-jitsu tournament recently, and there was a guy who was an ex-military vet who had lost both of his lower limbs due to an event in the military. Guy was out there on the mat in a jiu-jitsu tournament. Someone was about to go fight him and choke him out. And he showed up on the mat and fought multiple mats and he was good. This guy was legit. And so it just goes to show at the end of the day, you just gotta focus on your own progress. People are actually going to be cheering you on more than you realize. Don't worry too much and be self-conscious about those things. It's about getting after it and realize that the biggest critic is yourself. No one else cares. Only you really care. But the only thing that can really help you is actually taking steps on that journey. So... I kind of got a little bit of a soapbox there.

But ultimately, I hope someone can gain some motivation from that, because I'm not just someone sitting here as a researcher who studied these phenomenon, I've actually lived this. I know how much it sucks to be obese. I know how much it affects your self-esteem, especially in childhood. I know --- how much difficulty it is with all the information that people throw your way say, you should do this, you should do this, you should do this. Take all that information, take all the things that are consistent about what people are saying, and then find something that works for you. You may hear something I'm saying and say, oh look, I'm going to do what he said. Well, yeah, if you did it, it's probably going to work for you, but maybe it's not the approach for you. But you've heard something I've said, you've heard something from one of your other guests that "Jesse" has on here, or one of the other health experts, look at the common themes and then look around you for people who've actually been successful. - Don't look at the guy. - Take it for what it's worth. If you were to look at me when I was obese as a kid and I saw another kid and I started giving them advice on how to lose weight, he probably wouldn't listen to me. Should he listen to me? Probably not. - So you probably should look for people who actually have gone through that journey, who have actually gotten through to the other side and been successful and maintained it. Those are people who have really important information to share with you. Now, is that information going to be applicable to you universally? Oh, probably not, but it helps if you can find people who've done it successfully, learn from what they have to say, learn from the experts on this podcast. Find the themes of that that are universal, fundamental, and then apply the things that you can. They don't have to do everything, and we already talked about that, you can't do everything all at once. You just take the first step. That's the most important thing.

No, I think that was great and could be the most important part of this conversation because, to me, there's a couple different pillars that need to be addressed, and the information is just one piece. Having the motivation is the other big piece. And then I'll add to that and say, take action now. Because if you're motivated hearing "Andrew" right now, that may fade over the next couple of days. So if you're hearing his story, hearing this information it's resonating. Take action right away. Take that one step, build the momentum while you're motivated here, because that may fade and you might lose that opportunity. I actually suggest people to pause the episode right now, go out, put their shoes on, and go walk outside and listen to this. Because at the end of the day, motivation is just going to fade. I can promise you that. But you've gotta show up, you've gotta know what's going to work, you've gotta build consistent routines and just do it. You know the amount of times that even to today, if I go eat a ton of food, I'm going to go get massive, I'm going to blow up like a balloon. Trust me, I've done it. So I know what I'm talking about here. I still live this journey as someone who has abs. Right now, I exercise an hour and a half, two hours a day. - And people would think... Oh, I actually have an example here, "Jesse," for you. I went and spoke at a world-renowned obesity center about our research on the ketogenic diet and diabetes. And the head researcher at an institute is a huge name and said, yeah, because you haven't struggled with obesity before, you probably haven't experienced "XYZ." I'm like, I was clinically obese in adolescence for five years, and just the shock on their face, I'm like, yeah, I have to work at this all the time. I just developed tools that allow me to have power over the situation. It didn't go away from me... I'm just like everyone else. Just like everyone else. - But I show up every single day. I'm consistent. I don't always want to be, I can promise you that. Someone puts a pizza in front of my face, do I want to eat it? Yes. Yes, I do. But I also know the consequences of it. I know over the next few days -- that 30 minutes of pleasure is going to lead to 6... 12-plus hours of hell. I know that. It's usually about thinking forward. If I continue to make these same choices in my life, what's going to happen in one year? What's going to happen in five years, what's going to happen in 10 years? And do I want that? Because I can promise you, it's not going to magically change tomorrow, not unless you make a choice to change. I guarantee you. Because if that was going to happen, it would have already happened for you, and it hasn't. So the only way it's going to change is if you make a decision today to just do it. Don't overthink it. Don't even wait for it to be perfect. I promise you that day never comes. There's no day where it's just perfect, and it's just going to be perfect, and you just fall into doing everything you're supposed to do. No, that doesn't happen. You have to know that you got to show up and you have to be consistent and you have to have the right lifestyle techniques. And also, by the way, you will stumble and hit your face a few times along the way. You just got to get back up and keep walking. Most people don't. So if you can do it, you'll get further. That's all you got to do. Get up, keep walking. Get up, keep walking, and go. Don't wait, just do it.

I want to come back to the "CGM," "HbA1c," and make sure we highlight the point we're trying to make there. The fact that if you're seeing changes there, the time to act was actually yesterday, a quote from you. What I want to bring up in that realm, what is the one test somebody can do objectively to see where they're at? Is it fasting insulin? What would you say to that person who is in that phase right now where they're wondering, am I heading down this path, early stage? And they want an objective test just to see where they are. I would say periodic testing of fasting glucose and insulin, because it also gives you a "HOMA-IR" scale, which is a measure of insulin resistance. However, if you really wanted me to say the gold standard, I would get an "HbA1c" test, and I would also get a fasting insulin test. - But fasting glucose and "HbA1c" are just choices along the spectrum of what might be more telling and more optimal, because a fasting glucose can change due to the meal you ate the night before, whereas an "HbA1c" is a measure over a two to three month period of time. So it's much more... It's less influenced by subtle acute changes. So in that way, I would say a fasting insulin and an "HbA1c" because everyone can look in the mirror everyone knows what's normal body weight and what's not normal body weight. You often hear in our world that skin tags are a sign that somebody is headed down this path. Have you found from your experience that is true, and does it come way too late? I don't know anything about that, if I'm being totally honest with you. I have heard about that and they describe it's associated with insulin, but honestly, I have no idea.

All right, we'll leave that one then. I want to come back to insulin resistance. When we were deep into that, you mentioned that when it comes to chronic disease, it was a big player, but there were other players. I'm curious, what would you consider other big players in that realm? Yeah. So it's hard to really say what the universal problem is. A lot of people get very upset when people say, well, it's metabolic dysfunction because they're like, what does that even mean? Well, then you can get down to the mitochondria. Is there mitochondrial or energetic disruption? "Martin Picard" is someone who's written an entire book about this concept and has talked extensively about it. He's a professor at Columbia. He does a lot of research on mitochondria. There are disruptions in energy that is a pretty universal concept. We know that there's elevation in insulin and insulin resistance with some of these major conditions. We also know that elevations and chronic elevations of blood glucose levels can also be problematic.

But... I guess the question for a lot of people would be asking, okay, these are things that are early signs of things going in the wrong direction, "Jesse." But what do I do about that? And what I do about that can also give you clues. So we know that dramatically reducing the things that cause glucose exposure into the blood at very high and variable levels, or things that will cause insulin levels to be spiked or released at higher levels, are solutions to many of these problems. Now, for whatever reason, that's controversial. When someone says if you lower your carbohydrates in the diet, because that's the most common and potent way to elevate glucose and insulin in the blood, that that becomes controversial. I think the only controversy to that, "Jesse," is that people would contend, through maybe some false argument, that one is superior to another tool that may also work. Look, if there's another tool that works, awesome. There's multiple options in the toolbox. But there's nothing controversial about looking at the ability to reduce carbohydrates in the diet. Carbohydrates increase blood sugar levels, they increase insulin levels. And yes, if you reduce them, if you have one of these conditions we spoke about, you can reduce glucose and insulin. And if those are the driver of your condition, you can reduce those as well. Now, this may seem like I'm getting a total tangent from what you asked, but it's not.

What you have seen is that when we were analyzing athletes, of all people lean, normal body weight, highly active athletes we were seeing that some of these athletes on high carbohydrate diets were developing prediabetes, up to 30%. And what we found is that when they reduced carbohydrates, they were able to eliminate all blood glucose levels consistent with prediabetes. So they resolved their prediabetes glucose levels almost immediately. And when we were trying to understand, what is driving that? Which is to your question, what is driving this adverse change? Why? I reached out to other researchers, we pulled all our data. I was looking at various biomarkers that were associated with these rising glucose levels. We were seeing arguably the people we thought were immune to these type of conditions, "Jesse." And what we found was that it wasn't their body mass index or an index of their body composition. It wasn't that. I thought that was definitely going to come out as a signal, it didn't. It also wasn't necessarily age. Age was only a very small factor. It was associated with it, but it was a very small factor because as we get older, we suspect glucose levels would be more at risk for being elevated due to insulin resistance as we age. But that wasn't it. It wasn't fitness level in the concept of a biomarker of "VO2" max, which is your maximal aerobic capacity, a measure of fitness. The amount of carbohydrates that these athletes were consuming during the day was the strongest predictor, explained over 30% of the rising blood glucose levels we were seeing in these athletes. So what people were consuming during the day in the form of carbohydrates was actually predicting the changes they were seeing when they weren't eating. Do we know why that is? No, we don't know why carbohydrate intakes during the day are causing, in this case, individuals that we thought would be immune to these adverse health consequences from the food environment to develop elevated glucose levels consistent with prediabetes. We never thought that'd be the case. And nor did I suspect that the carbohydrate intake they were consuming because when you look at what they were consuming, it wasn't necessarily unhealthy. It was completely aligned with the sports nutrition guidelines for athletes today. Completely aligned with it. Average carbohydrate intake was slightly above 350 grams per day. These individuals were very fit, high VO2 max active athletes. But they had prediabetes glucose levels. And they resolved it by reducing the amount of carbohydrates in the diet while keeping activity, body composition, and calories consistent. So it was just this change in the macronutrients. So that then lends a theory not a proven one, but a theory that the amount of carbohydrates being consumed in the diet for some individuals, again, I only said 30% of athletes, I didn't say 100% were developing glucose levels consistent with prediabetes as carbohydrates started to elevate. And I will tell you, for most people in the nutrition world, dietetics world, exercise physiology world, their mind would blow up thinking oh, carbohydrates are causing diabetes. No, they're not. Then why was it linked? Why? Why? Why was it linked? The body composition in those athletes that had prediabetes wasn't higher, their fat wasn't higher, their fitness level wasn't uniquely higher or lower. They weren't that --- much older or younger, they were right in the middle of the cohort. Nothing else explained it. Now, we didn't have all their biomarkers, we didn't have their genetic background, which could have been a risk factor. We didn't have a lot of things, but we had some pretty important signals that we know are associated with it. And it did pop out that carbohydrates were the strongest predictor of elevation in blood glucose levels during the fasted state. So... that lends a theory that these type of foods are causing some individuals to develop prediabetes. In fact, we've seen that at the top end of elite athletics. We've seen individuals, the prior Ironman champions getting diabetes largely explained at least through their own lived experience, anecdotally from their diet. Because keep in mind some of these athletes, according to sports nutrition guidelines and, honestly, if you look at the prior dietary guidelines of America, they're all pushing very high carbohydrate intakes. Now I'm not going to sit here and tell you that carbs are evil. In fact, some of our research shows that carbs can improve performance. But it's not about carbs being evil, it's about the precise dose of them to be aligned with the physiology and mechanisms we know drive the changes people want to see. That's it. It's about being precise. It's not about a universal blanket statement that they are good or evil. That's not true. They are a tool just like anything, and the amount matters.

So back to your original point, when we talk about things that may put someone, let's say, at risk, or things that they could look at, or things that they could monitor to adjust. -- I think people could look at the various biomarkers we spoke about. But one of the things that's emerging is the dietary choice that people are making. Because not only can it resolve the issue, but now we're having evidence that it's associated with the incidence of adverse outcomes in metabolic health, even in people we thought would be immune to it.

Okay, to make sure I understand this correctly, these athletes are consuming carbs, they are performing, so utilizing more energy assuming, than the average person. But fasting blood glucose was still elevated because of the carbs they were taking in. So... if I were to say a very blanket statement in layman response, I would say generally, yes, that is what we observe. But there's some nuance there. So we don't know the carbs... caused the elevation in blood glucose levels. What we know is that when people reduce the carbohydrates, it resolved the elevations in pre-diabetic... glucose levels. We also know that when we looked across seven different analyses in athletes who are wearing these continuous, every-five-minute monitors of their blood glucose to get a high resolution on their glucose levels, that the strongest predictor of rising glucose levels when they weren't eating, which is the basal metabolic state. So the fasted state, which is where people look at to see if there's changes in your metabolism absent of other factors. We were seeing that carbohydrate intake was the strongest predictor of that. So this is again illustrating a consistent theme that that higher carbohydrate intake is one, when you reduce it, it eliminates. Two, it's linked more than any other biomarker that we were able to assess to the rising glucose levels. And we know that, physiologically speaking, that if you consume more carbohydrates, your blood sugar elevates, your insulin elevates, and then again, if you do that in excess, that there's problems that arise. But again, these athletes weren't doing it in excess. They didn't gain any weight. They didn't gain any weight, they were lean the entire time. Their activity was controlled, their calories were controlled the entire time, and their body weight was controlled. And they still developed pre-diabetes just from a macronutrient shift. So... what we're illustrating here is not necessarily a causal A to B relationship, but a very consistent kind of central and consistent theme that, yeah, what you're choosing when you consume a diet can have a pretty powerful impact. But to support that theme was one of these major analyses from Duke and researchers in the United States and China. 30, I think 34 or 36 different countries, over 4,000 different subjects had really refined assessments on nutrition, energy expenditure using these techniques called deuterium-labeled water. And what they were finding is they were trying to understand what was the cause of the obesity epidemic. Was it the diet, a lack of activity or something else? What they found is that the diet explained over 90% of the obesity epidemic observed across various parts of the globe. So, yes, it does seem that the diet is driving things like obesity. We know that diet can be a contributor or causal relation not causal, but linked very strongly to diseases that can be reversed by lifestyle like diabetes.

So, that's a more nuanced way of describing to your audience that in general terms, if someone were to take something away from this, they may take away exactly what you said. But it's also important to illustrate where we actually stand with some of the information and data, so that when people are exposed to new information, they're able to assimilate that more accurately. Because they'll probably hear me say something, they hear someone else say something, and say, well, they're just saying two different things. It's like, well, no, take the nuance of what I said, and hopefully the other person gave some nuance as well. And you can put all those pieces together to come up with a better puzzle and a better solution to what's happening.

When these athletes were on the carbs, they weren't fat overall. Do we know if they were gaining visceral fat? Well, the study was over a four-week period, so almost certainly they wouldn't have. And their body composition, their body weight didn't change, so it'd be very unlikely that they would have had a massive shift in the type of fat they were consuming. Because keep in mind, their inherent diet they were consuming before they started the study was a high-carbohydrate diet to begin with. So, they were already consuming, on average, a high-carbohydrate-based diet. And so, we didn't dramatically shift those athletes away from that when they went onto that diet, but it was a pretty profound shift when they went onto the ketogenic diet. --- Very unlikely that it was associated with visceral fat. But to be fair, we didn't do an "MRI" scan, but it would have been unlikely that was the case. And refresh my memory, what kind of exercise were they doing? So, these were runners. So, this was middle-aged runners who were avid runners. And the minimum criteria was to run at least 50 kilometers per week. They had to have a high enough "VO2" max to be very high levels of fitness. - They all happen to be very lean, normal body weight. And most of them, actually, I think all of them were competing in local or national tournaments for running.

Okay. And then take me into treatment and how quickly things changed. So --- we did a randomized fashion, so individuals either went on a high or low-carb diet in a randomized fashion. And we controlled a bunch of variables to ensure that we were just looking at whether the diet-induced changes were real. And the athletes went on a diet for four weeks. So, they went on a diet for at least four weeks. That's very, very, very important because a lot of studies that show changes, diet-induced changes, we see that a lot of those changes are still happening within the first three weeks. So, we wanted to get to four weeks so we can see a lot of those changes get back to homeostasis or normalize, so we could actually test the effects of the diet on changes. So, they went on one of the two diets initially, and then they took time off the diets for multiple weeks and then went on the other diet. So, these athletes were doing this intervention for roughly around 12 weeks. You have a familiarization, early testing, four weeks on a diet, you're taking at least a couple weeks off the diet, and then doing the other diet in a randomized fashion across the board. So, same person. We're controlling their genetics and environment as well. -- And when they went on the high-carbohydrate diet, just like they did with the low-carbohydrate ketogenic diet, they had a registered dietitian monitoring them, giving them guidance, nutritional advice. All these are very consistent with sports nutrition guidelines. So is the very low-carbohydrate diet consistent with many of the thought leaders of how you perform and fuel on a very low-carbohydrate-based diet? So, we followed both those criteria, and they were monitored throughout. In fact, on the ketogenic diet, they were also monitored for ketone levels as a measure of compliance. And we also had continuous glucose monitors. So, we were measuring how they were adhering to the diet. So, someone's on a ketogenic diet, but all of a sudden at 12:00 at night, you see a spike to 200. -- I don't know, were you adhering to the diet? This is where questions may arise, and we try to come up with a rationale to make sure the athletes were actually adhering to the diet. But this is our way of actually confirming they were on the diet. So, that's what the study looked like. - Across both of these studies, though, the glucose levels that we were measuring was from continuous glucose monitoring. We also measured "HbA1c," insulin levels, a bunch of other cardiometabolic biomarkers. --- But we really wanted to look at the continuous glucose monitor levels as a measure of metabolic health. And the reason we want to do that is because we know that things like "HbA1c" don't reliably change completely until around at least two months. And the study was four weeks on each diet. So, we knew that a fasting blood glucose levels would be insufficient, because acute changes over 24 hours can change fasting glucose levels and exercise, or even the meal you ate the night before. We didn't see much value in an oral glucose tolerance test here because that's a whole 'nother laboratory visit, and you have to control a bunch of environments the night before, just like with a fasting glucose test. So we chose a continuous glucose monitor because it allowed them to live their normal life and we could capture their entire fasting glucose levels, not just at one single time point, but... every five minutes, 288 times per day, thousands and thousands of times over the entire study duration. It gave us way better resolution on what was happening with their glucose control, not just in the fasted state. But... in their food dynamics, how they're responding to food, how high they went. And so we were able to look at their entire glucose control over the entire circadian clock... so from sun-up to sundown.

Let's talk about their performance throughout. So what we were monitoring is athletes were asked to adhere to a very strict activity protocol because we wanted to control activity as a variable. A lot of studies that look at performance or diet-induced changes, they'll be changing their calories, they'll be changing their activity level, they'll be losing weight. Those are all things that are going to affect someone's metabolic state or their performance, which is also something we're looking at in this study. And what we wanted to do at this stage was we said, okay, well, those are obviously huge confounders on the study outcomes. But we really wanted to test whether there was a macronutrient-induced change. If you just shift around the calories but keep the calories consistent, is that inducing an effect? Because that's something that really hadn't been answered very well in rigorous randomized controlled trials. So... we controlled all of those variables and luckily we had a very adherent group of individuals. You don't often get that. And they stuck through this for over 10 weeks, start to finish. And... what we wanted to do, and it was really the impetus of this study, is we wanted to understand what happens when we take these athletes and we put them on these grueling assessments. - A one-mile time-trial test or 6x800-meter sprints. Now I don't mean they went and ran a mile, -- your audience is like, oh, I can run a mile. That's not grueling. No, no, no, no, no, no, no. I mean run the fastest mile of your entire life. That's what we're asking you to do, run a mile. So somewhere between four to seven minutes as fast as you possibly can. Most of the audience listening to this will not be able to even do this in sub-seven minutes. - It's a grueling endeavor... A grueling endeavor because it's long enough to be impossible to ignore the pain, but you have to push extremely hard the entire time and grind that out. So it was a one-mile time trial and 6x800-meter sprints. And what we saw is, historically speaking, "Jesse," we would expect that in these very intense forms of exercise sprints, these one-mile time trials that you would be almost completely relying on carbohydrates as a fuel source. But what we actually saw is that individuals who were on these very low-carbohydrate ketogenic diets were performing exactly the same in fact, non-significantly better than those on the high-carbohydrate diet. The same athlete too, by the way. So the question was, are carbohydrates really essential to performance if -- we are doing an exercise bout that's intense enough to require, quote-unquote require carbohydrates? Well, obviously, it wasn't requiring carbohydrates because when we actually measured the amount of fat and sugar or -- what we're saying here is carbs as energy, we saw that at these very high levels of exercise intensity, that fat made up the majority of fuel at over 85% of someone's "VO2" max so, maximal aerobic capacity. Exercise textbooks, exercise guidelines would say that carbohydrates would be the predominant or essential fuel during an exercise intensity that high. But what we observed is that individuals who adapted to a ketogenic diet for sufficient. So at least four weeks in duration that they were able to observe that their ability to perform was equivalent to high-carb, and they were able to fuel that predominantly with fat as a fuel. This fundamentally flipped the way that we looked at fueling athletes with these various diets. Because keep in mind, when we talk about these ketogenic diets, "Jesse," a lot of times you'll hear this from the athletic community and say, well, that sounds great, but it’s going to cause a negative effect on our performance. And we said, okay, well, that sounds interesting, but no one's really done a study that controlled all these variables and actually answered that direct question... So let’s try it. And to our shock they performed exactly the same. Which means, wow, now I have a choice. Now the diet I choose isn’t going to determine whether I perform better or not, but it may have metabolic health consequences... Because what we were seeing is that 30% of the athletes on the high-carb diet—were developing glucose levels consistent with prediabetes. And when they switch over to a ketogenic diet, all of those athletes resolve their glucose levels into normal range. They resolve their prediabetes. But then we need a follow-on study, "Jesse," because a lot of the feedback with that is oh look, these short-duration, intense exercise bouts. Yeah, well, maybe during something that’s short, it won't, fat’s fine. - Even though before they didn’t say it was fine, but now -- it’s fine. But what about these Ironman-type of events? What about these long-duration aerobic exercise bouts? There’s no way they'd perform the same if you need to oxidize carbohydrates throughout to maximally perform and you need muscle glycogen to perform on these exercise bouts. So we did another study... We said, that’s a really good question. We haven’t actually answered that question... We’re going to recruit Ironman competitors. We’re going to ask Ironman competitors to adhere to a diet for six weeks. We’re going to do the same thing put them on one diet in randomized fashion, control the same variables, cross them over to the other diet after time off of each diet... and let’s see how they now do in a time-to-exhaustion trial. So we’re going to ask them to do 70% of their "VO2" max and sustain it for as long as humanly possible... until they could no longer go, until they hit the wall. They bonked. And so athletes were doing this. We had athletes go up to some of them over four hours. But what we found is yet again that when athletes reduce their carbohydrates to less than 50 grams per day, they saw no deterioration in performance. Their performance was exactly the same on the ketogenic diet versus the high-carbohydrate diet. This goes against so much of the sports nutrition guidelines and ideologies that push these super-high volumes of carbohydrates as virtually essential to perform... And what we’re seeing is that’s not the case, even in Ironman competitors in long-duration rides. And... what we also observed is that we were looking at the advanced biomarkers that would predict changes in metabolism. We were looking at continuous glucose monitors and ketones. And what we were observing is that many of these circulating metabolites in response to a ketogenic diet would not reach normal homeostasis until after the three-week time point. So around the four-week time point this is the same time point that we were talking about, "Jesse" that was linked to performance normalization on the ketogenic diet. Because so many of these studies before were three weeks or less. They were looking at individual biomarkers of a ketone elevation or fat burning going up. Yes, that happens pretty quickly. But we know that circulating metabolites since the 1960s don’t normalize on very low carbohydrate interventions for weeks. And what we saw for the very first time is that when we monitored the circulating... brain metabolites... in the form of ketones and glucose, that they came back up to normal after four weeks. So this then brought up the idea of what was the key driver of performance outcomes? Well, we did one more thing with that experiment. We then gave the individuals... just enough... glucose after that to see if just trickling enough glucose, not to change glycogen levels, because you need a lot of glucose to do that. Not enough glucose to change the entire landscape of how your body burns fat and carbs. Because when you consume a lot of carbs, your body starts shifting to burning a lot of carbs... What we did is we just trickled in enough glucose... 3.4 grams, actually 3.4 grams... every 20 minutes. So a teaspoon of sugar every 20-minute window. So a tablespoon every hour, basically. - So basically nothing... like -- go take a big teaspoon and put a little bit of sugar on it. That's what we're giving every hour. Not one of these "Gatorades" or gels or some people are recommending that you consume 90 to 120 grams per hour, which is basically the equivalent of an entire loaf of bread. So imagine eating an entire loaf of bread every hour while you're exercising. And that’s what some people are essentially recommending in carbohydrate content. But we just gave enough to trickle in to maintain blood glucose levels in the normal range. Because the thinking was, well, if all we're doing is not affecting the amount of carbohydrates that are being burned in the body... and not enough to change muscle glycogen what we're actually isolating out and determining is whether a change in maintaining normal blood... glucose and ultimately brain energy could do... And we saw just giving 10 grams per hour, six to nine times lower than current recommendations for carb intake we saw a 22% improvement in performance. Now, that was kind of mind-blowing because in that same experiment, we did this on both low and high carb diets, and they both saw improvements in performance because both

avoided hypoglycemia. But yet one diet, the ketogenic diet, had low carbohydrate content and was burning less carbs and more fat. So it wasn't the amount of fat or carbs they were burning because each diet had completely distinct levels of each they were burning, but that they performed the same. It wasn't the amount of muscle glycogen either, because we know that ketogenic diets, at least in four weeks in duration. All studies with athletes have shown reduction in muscle glycogen, but they performed exactly the same. So it must not be the muscle glycogen.

So what we had been doing over the last five years is we had been looking at what was the key determinant of exercise performance. Because every time we would look at these studies in a rigorous randomized controlled fashion and ask these questions, we were coming up with answers that showed that the amount of carbohydrates someone was consuming -- was not predicting performance. And what I mean by that is when you had to give enough carbohydrates to change glycogen or carbohydrate oxidation levels. So how much sugar you burn and muscle glycogen or how much carbs you load up with to fill up your muscle before a race did not seem to predict performance. But that's what everyone's recommending. That's what the sports nutrition guidelines recommend 5 to 12 grams per kilogram of carbohydrates per day. On top of in athletes who are normal body weight in some males, that's over a thousand carbohydrates per day. Over a thousand. Keep in mind, we saw levels at just, on average, 350 where middle-aged runners who were fit, normal body weight were developing pre-diabetes, 30% of them were at 350 grams on average per day. And some of these are pushing up to a thousand. So that's astronomical.

So we were looking back at all the data that said, where did this come from? -- Where's the data on this that shows that they're pushing this? Because it must be from somewhere. Well, we look back in the -- literature and we were finding all the way back to the 1890s, the Olympians all the way up to 1970 were essentially consuming fat and protein focused diets. You can look at the cafeteria records of Olympic athletes, the catering orders. It was a fat and protein --- heavy diet. But in the 1960s, or, sorry, the 1970s, there was a major shift in mindset. Well, in the 1960s, right before this, there was a famous physician called "Jonas Bergström" who developed a muscle biopsy technique called the "Bergström" muscle biopsy, where he put a needle in the muscle and pulled out muscle tissue and put it into an analysis and found that, oh wow, look, there is muscle, there's glucose stored in this muscle tissue. It must be important to performance if it's stored in the muscle. So then they gave a ton of carbohydrates, found that more glucose was being stored in the muscle and that more glucose being stored in the muscle was associated with longer performance.

Then in the 1980s, '70s and '80s a researcher called "Coyle." So C-O-Y-L-E or "Coyle," however you want to pronounce it. - Was discovering that there was this new technique emerged where you could actually measure the amount of oxygen being consumed, the amount of "CO2" being expired. And that ratio would tell you how many for carbs and fat they were burning. And what they were seeing is, wow, when they consume more carbohydrates, they burn more carbs. And the amount of carbs being burned was linked to better performance. Now keep in mind, they never causally proved it. They were just showing associations. But then in the 1980s, there was a concept called the crossover effect that was developed, and it's been sitting in the exercise textbooks for the last 40 years, which showed that as you get higher and higher levels of intensity, that you rely more predominantly on carbohydrates as a fuel source. And that is a hundred percent true, "Jesse," that as you get higher, you rely more on carbohydrates. And then as you get higher in intensity, you can use less and less fat as fuel because it becomes more anaerobic. Think about someone sprinting, you can't really breathe if you're doing a max-effort sprint. You can barely breathe, but you feel like you can't gasp for air. That's what we're talking about here. -- Now... that was prevailing belief for years, but again these were all based on associations.

Then in the 2017 through 2021, there were three separate studies by a very prominent group, "Louise Burke's" group and "John Hawley's" group that showed that just comparing ketogenic diets to high-carb diets. And what they saw is that these elite-level Olympic race walkers who went on a ketogenic diet saw a reduction in performance. It was only 2%. So for most individuals, 2% is completely unnoticeable. But it made headlines all over because 2% can be the difference between first and second place in an Olympic athlete. But... most of those studies actually didn't show inherently a performance decline. What they showed instead was a reduction in exercise efficiency. So in a measure of how much these athletes are actually able to perform over a set period of time. And what they were also showing is that they were showing these marginal reductions in performance. Now keep in mind, those studies from 2017 to 2021, essentially they said it in their own manuscript put the nail in the coffin that carbohydrates were important for performance, that low-carbohydrate diets would impair performance. However... those studies were... five days to three weeks in duration. Not a single one of them ever went to four weeks in duration. Despite knowing since the 1960s that key circulating metabolites for things like the brain don't normalize when you shift on a diet for at least, at least over three weeks. So four weeks in duration.

So we then conducted these randomized controlled trials. We were seeing that not only just us, but others were seeing that if you sustained the diet for sufficiently long that you were no longer seeing these performance declines anymore. And -- this then led to this theory of what is actually driving performance? And so we had actually pulled virtually every exercise study that ever administered carbohydrates. And for over a hundred years so over a hundred years of evidence we looked at 600 different citations, over 160 different performance studies took over five years. And when we looked at why carbohydrates were improving performance, what we saw is that when carbohydrates improve performance, "Jesse," 88% of the time it did. It wasn't the carbohydrate group that had a massive change in their biomarkers. It was the placebo group or the non-carbohydrate group that was seeing a reduction in brain energy metabolites in the blood. They were seeing drops in blood glucose levels. Those studies back in the 1960s and 1970s by "Bergström" and "Coyle," they also showed a reduction in blood glucose levels. But they didn't blame it on the blood glucose levels. They blamed it on the amount of muscle glucose in the muscle or the amount of carbohydrates the body burns. Despite knowing that a drop in blood glucose levels has a certified, well-known mechanistic neuroendocrine counter-regulatory response that impairs performance to preserve brain energy.

And so what we were finding is that the overwhelming majority of time it wasn't reliably that the carbohydrate or the amount of glycogen in the muscle predicted performance. It wasn't the amount of carbohydrates being burned that predicted performance. It was the amount of brain energy metabolites circulating in the blood present that was reliably predicting, or was the predominant primary predictor of performance, or if someone got early fatigue. And that fundamentally shifted the way we think about this, because what it fundamentally showed for the first time, to our knowledge, is there's two distinct pools of glucose in the blood. There's the large glucose pool, which is the muscle, and then there's a small glucose pool which is the liver, which holds glucose as glycogen, and the circulating amount of glucose in the blood. Again, you only have about five --- grams of glucose circulating in the blood at any one moment. Basically the equivalent of a teaspoon of glucose at any one moment. So it's a very small amount there that's present there but yet when that is reduced even marginally, you can see dramatic reductions in performance due to an established neuroendocrine counter-regulatory response to preserve and protect the brain. However, the large glucose pool is what's gotten almost all the attention because people focus on muscle glycogen or the amount of carbs the body burns. And as you pump your body full of carbohydrates at super-high levels, the body fills up these large glucose pools. And people believe, well, obviously if I just fill the muscle with more glucose, it's going to predict my performance. But yet it did not reliably predict performance. In fact, one of the best ways to tell us is they've done genetic manipulation of pre-clinical models, animal systems. And what they found is that individuals who basically have an over-expression or an overabundance of muscle glycogen, they don't perform better than those who don't. So you overload the muscle with glycogen in these animals artificially through a genetic manipulation. The best type of science someone could possibly do is genetically modify something as a single variable and determine if it has an effect. And they've done this and it didn't improve performance. But if you actually overload the liver so you genetically manipulate till you can fill the liver with glycogen but not the muscle that did improve performance again through a genetic manipulation. So this is one of the cleanest ways to actually get at that question. But that's in pre-clinical models. And so they may say, well, that's pre-clinical animal models that doesn't apply to humans. But yet when we looked at 160 different performance studies, 88% of the time it was this circulating amount of the small glucose pool the amount in the blood and the liver that was predicting performance, whereas the large glucose pool as a distinct pool was not reliably predicting performance.

And so that's really the impetus of a major paper that was just released in "Endocrine Reviews" actually, very recently. - Essentially showing this over a hundred years of evidence 600 citations, 160 different performance studies, and really a five-year haul of effort to try to understand what was going on and what was actually predicting performance and try to get clues as to why carbohydrates are manipulating metabolism and why they are manipulating performance, and also get at, is it this large glucose pool or is it the small glucose pool? Because if it's the large glucose pool, then yes, the sports nutrition guidelines are right you need to load up an abundance of carbohydrates. But if they're wrong, which our evidence shows that they are. Then all you need is the amount of carbohydrates required to maintain the small glucose pool, which is infinitely lower. And as a result, athletes may start to ask some really important questions. If it's the small glucose pool that predicts performance, do I need to have these astronomical amounts of carbohydrates that the sports nutrition industry is telling me I need? Do I? Do I need to consume literally 120 grams of carbohydrates for four to six hours straight on my ride? Or do you need less than that? Because it's consistent with the small glucose pool that we reliably see as the strongest predictor of performance. Now I also want to acknowledge here that the small glucose pool is not the only thing that predicts performance. We know that when athletes hit the wall. Eventually, that even when you completely prevent hypoglycemia by giving a sufficient amount of carbohydrates, they will eventually hit fatigue. So just because you maintain normal glucose levels forever doesn't mean that you're going to prevent fatigue. There are other factors that are secondary to the small glucose pool that also affect performance. But the primary predictor of performance, particularly in these long-duration efforts over a two-hour ride of any type of strenuous activity, is this small glucose pool. And that's consistent with multiple meta-analyses, "Jesse," that I've looked at for resistance exercise where resistance exercise is more of an anaerobic-based exercise and carbohydrates don't improve performance in that either until you get past 45 minutes in duration and it needs to be a strenuous form of it. So typically, leg-based resistance exercise. So again, all showing the same exact consistent phenomenon.

But it makes total sense because when you actually understand how the body tries to protect itself, what's the most important tissue? The brain. The brain, without a doubt. When the brain senses low blood glucose levels, it does everything it can to shut down all the systems that will eat away and starve the brain from that glucose. And what does it do? It stops activity. - Another key example of this is when ketones elevate and lactate elevate. Those are typically signs within the body that you're in a caloric deficit or a high energy expenditure state. And when those are present in the blood, the brain eats them preferentially over glucose even all the way down to the receptor, "Jesse." The receptor for ketones and lactate allow for passive diffusion into tissues to be burned and utilized. Whereas glucose, in many tissues, requires active transport. It requires active transport in the form of insulin for glucose to get into the muscle. Why? Because it only is going to the muscle in abundance. It's not essential, it only goes there in abundance. - Because insulin actually goes to the liver first to restore liver glycogen and the small glucose pool. Why would it go to the liver first, "Jesse?" Because it's protecting the most important tissue in the brain from being energy deprived. If the muscle was the most important tissue, then it would go there first. And guess what? It doesn't. 66 to 75% of insulin that's released from the pancreas goes through what they call the hepatic portal vein straight to the liver, and it goes there first. And when it goes there first, it binds that tissue, and that eats the overwhelming amount of glucose. And it does it to protect you. It protects you from going into a brain energy deficit, which is critical to save your life. At least historically it would. Nowadays you're like, I'm just getting hypoglycemic. Let me go eat some orange juice. Well, guess what? Before, there wasn't orange juice sitting on the sideline. - So it did everything it could to protect you from that deficit. And all the mechanistic and physiologic rationale has been elucidated in this review that explains exactly why that is. But it's there as an evolutionary protective mechanism for the brain, which is why even small micro-amounts of glucose are able to dramatically improve performance, equivalent to what we see in these other studies that give astronomical amounts of carbohydrates. It's also why, "Jesse," when you look at dose-response studies in exercise where you give, let's say, 30, 60, or 90 grams of carbohydrates, you do not consistently see a performance improvement once you give some carbohydrates versus a lot more. Why is that? Well, if it was the large glucose pool that was important for more muscle glycogen and carbohydrate oxidation, then the more you gave, the better performance would be. But yet we don't consistently see that. Why is that? But we do see that if you give some carbohydrates versus none, so long as the exercise is sufficiently long to induce a drop in blood glucose, carbohydrates reliably improve performance. 88% of 160 different studies that have looked at this. So I'm off my soapbox. It took us five years to actually analyze that. And I hope the sports nutrition industry will pay attention to this, because what we're also seeing is that these heavy amounts of carbohydrates that are being pushed onto athletes is not for free. It's not for free. Some of these athletes are developing adverse metabolic changes. One of the most prominent examples is a gentleman who came out publicly, his name's "Lionel Sanders," a world champion Ironman competitor. He went on to eventually develop, following the sports nutrition guidelines. Super lean, exercising sometimes four-plus hours per day. Pre-diabetes. He was fatigued, lethargic, wasn't recovering well, went to the doctor, got his blood work back... Everything looked good except for his glucose levels were going into the pre-diabetes range. So he had developed pre-diabetes. He changed his diet, reduced these ultra-processed forms of carbohydrates in his diet. Boom. Almost immediately, his glucose went to normal. He went on to win an Ironman championship. ---

The point here is that this review, through a number of our work and 100 years of evidence, is essentially showing for the first time ever that there's these two distinct forms of glucose pools with very important, distinct effects on the body. One with a clearly more important role in the body regulating performance, but also preserving your brain energy and your brain's metabolism. And as a result, it also has impacts in performance. And we see that it makes sense that the brain would drive performance. It isn't all about the muscle, "Jesse." A lot of physical performance, is also about the brain. All right, that was fascinating. Very detailed. My question to you after all that, from the research you did, research you looked at, for the athlete out there wanting to get practical with this, distill it down in the most general sense. So athletes that are doing over 60 minutes of strenuous exercise, whether it be aerobic or anaerobic exercise, they can benefit from carbohydrates. It's a tool. But the amount of carbohydrate you probably need is much lower than you've probably been told. We see that even just as little as 10 grams is sufficient to potentially do this, maybe up to 30. Excess amounts beyond that may not have any additional benefit. Now if it's less than 60 minutes in duration, it doesn't seem to have much of a performance impact for these athletes. And that's the practical advice at the event itself, at the training session itself. But don't negate your actual diet that you're consuming over the 24 hours of the day. Every study that has looked at these effects has done so while controlling these key dietary factors, activity factors, etc., etc. So if your diet's all messed up and you have to consume. Let me give you a perfect example on these "Peloton" rides, these Tour de France rides where they're doing four to seven plus hours on back-to-back days, they're pushing 120 to 200 grams of carbohydrates per hour. And people will point to that as an example and say, hey look at these guys. They're the best in the world. They're doing, 120 to 200. Well, yeah, guess what? They're on a bike for four to seven hours every single day, and they need to consume astronomical amounts of calories. When are they going to consume them? Some of them have to be on a bike. That's the most extreme example of all time where they're actually consuming their diet on a bike. Whereas in these other examples where people are going into exercise for different bouts and they're not doing it for back-to-back days like a Tour de France ride, which is the most extreme thing there probably is in athletic performance. --- They're preparing for an individual event, a marathon or an individual 5k, a 10k, a cycle ride, a performance bout. -- Maybe they're an athlete, they have a football game, they have soccer or any of these one things. They're not going for multiple days back-to-back, they're doing an individual performance bout, and then they have time to eat and recover outside of that. And that's where the overwhelming majority of their diet and calories come from. Again, these exceptions like the Tour de France are not the same thing we're talking about here. Those athletes, by default, logically speaking, have to consume calories during their ride. But what those athletes do should not be what everyone else is doing. - They're literally doing the most extreme sport of all time. And so that's an inherently different scenario. I can't tell you the amount of times I've heard this. But either way, for the average person who's listening to this, who isn't a Tour de France peloton rider what should you do if it's less than 60 minutes in duration? Carbohydrates don't seem to reliably improve performance. If it's over 60 minutes in duration, whether it's aerobic or anaerobic exercise, so resistance training, running, jiu-jitsu, yes, all those things can improve with precise amounts of carbohydrates, but probably a lot less than sports nutrition guidelines recommend, assuming you're getting sufficient calories on a well-formulated background diet that you consume outside of your training window.

All right, last question for today. What can we take from the research, apply to the average person who's not an athlete? Just looking at the physiology, somebody that just wants to lose weight and get metabolically healthy? I'm going to give you the three free tips anyone could have to try to improve their health. And these -- simple tips that work for everyone. And by the way, they're all free. No one's making money off this. This is just what works. Number one, athletes should eat whole foods. ---- Not athletes, but anyone out there should be focused on whole foods. You probably don't want to consume your food in packaged format. You probably don't want to consume liquid calories. You want to focus on whole foods as a set precedent that's going to eliminate so many of these food components and ingredients that drive hunger through the roof, that makes it easy to over-consume calories that are micronutrient-deficient. Eat whole foods from your diet, regardless of the diet. - If you want some added extra benefit you could get the additional benefits of things like nutritional ketosis by lowering your carbohydrates specifically. But focus on eating whole foods and reducing calories in liquid format. Number two, exercise. Any type of physical activity is better than no activity. So move. Try to do it. If you don't move right now, do a 30-minute walk. That's it, just a 30-minute walk every single day. If you can do that, do more. So any activity is better than no activity. More activity is better than some activity. And if you want to get very prescriptive and precise, then you can start talking about a specific amount of resistance exercise training days per week at least three, maybe upwards of five and aerobic exercise bouts. They recommend anywhere between around the same amount per week. But the more you do of it, the better it is, and there's usually a pretty clear dose-response of exercise. The more you do, the healthier you are across multiple biomarkers, the more you reduce your risk for most major diseases and mortality. All right, that's number two. Doesn't cost you anything. You can go outside and walk right now. You can go run right now. You can do pushups on the ground, you can do them on the counter, on the wall, you can start somewhere. Bodyweight exercises and walking it doesn't cost you any money, nor does diet, by the way, because you have to go spend money in the grocery store. It's about making a choice on what you consume. It's not about buying expensive food. It's about changing the choice you make in the grocery store. Not about buying new things or expensive things. It's about changing what you buy. And the third thing free is sleep. If people really want to prioritize their health, that's the third pillar. And how do you do that, and how do you do it for free? You wake up in the morning and you get sunlight in the morning. Now this is something that people talk about all the time. It's so trendy now. We've known this for so long that if you just wake up and get sunlight, that's going to set your circadian block it's going to... clock. It's going to help you go to sleep on time later in the day. Then when you get towards the end of the day, you want to reduce the amount of artificial light exposure you get so that you are more likely to fall asleep and feel rested. So it's about getting the right amount of sleep and the right quality of sleep. You getting sunlight first thing in the morning doesn't cost you a dime. You not looking at screens or TV right before bed doesn't cost you a dime. Those are the three pillars of health, well-formulated nutrition from whole foods, reducing liquid calories. Exercise, more is better than less. And sleep, focus on the free things. Getting out sunlight and reducing artificial light late at night. And by exercising, you reduce inflammation, you're able to sleep better. When you get better sleep, you're able to make better choices with nutrition because you're less impulsive and you're less inclined to overeat poor food choices. -- All these things interact with each other. If you avoid one, other things start to crumble. So focus on those three things. Those are the priorities. Nothing about it's fancy, and it works every time. Love it. Great tips there.

Coming back to that hundred years of research though, anything specific that we can pull from there and apply to the average person? Well, I think the message is pretty clear that you don't need to have an abundance of carbohydrates to function. You can function on. This evidence is just more reinforcement that people can choose the diet of their choice in a well-formulated format and function. If elite athletes or high-level athletes can choose what diet they need and perform the same, then certainly an individual who's not worried about their race time can do the same. - And so this idea that anything is essential is... the thing you should be focusing on is ensuring you get adequate protein, essential nutrients in the form of fat, and the rest of the calories can be made up with, ideally, whole food nutritious components of your choice. So... but there's a lot of things that come out of this article. We really focused on the practical take-homes for the average person. -- There's so many things that we had to go through in this article, "Jesse." We went through 16 different points knowing full well when we were seeing this evidence and having to review all this data, and what we were finding, that we needed to address every single stone and turn it upside down... What we were essentially seeing is that one thing that we also found here, which is also applicable to an athlete-specific thing. But I think it can apply to other people is that. And this kind of gets to food labeling and food packaging and what people's choices they make in the grocery store is a lot of the recommendations that athletes are given from let's say, sports nutrition industry. Let's say you go to the grocery store and you look at the front of a package and it says... zero sugar, keto friendly. And you're thinking this must be healthy. Well, not necessarily. - Because the same thing has been applied in the sports nutrition world where they said, have this drink, it's going to help you perform better. And -- "Gatorade's" in front of -- some of the healthiest people in the world... And it makes you look like they're doing these really important forms of exercise and they're super healthy and they're functioning great with this "Gatorade." Not hating on "Gatorade." There's a ton of companies that do sugar water and gels and crap. But... either way... what we're finding is that when these athletes consume these prior to exercise at very high levels, they actually... spike insulin, they block fat oxidation, they... accelerate muscle glycogen breakdown. The sports nutrition industry has said, -- you consume these to prevent muscle glycogen breakdown. Spare it. No, you actually break it down faster when you exercise with consuming these things. Yes, you can resynthesize it afterwards... with high amounts of carbohydrates, but you actually break it down faster... So one other theme that comes out of this is just you have to be your own advocate. You have to be your own advocate for what works for you and and and try to avoid putting trust into things like food companies or sports nutrition industries and other places to quote-unquote give you the best guidance and advice. You have to look for the trusted resources, look for examples of what's worked, and follow... or take the information that you're seeing... as helpful... in those examples and apply it to your own life. -- But if people are interested in learning more about that, it's a pretty extensive article... We summarize everything in the first 16 points in the first introduction so people who can't read the whole thing... we try to make it easier for them. We also put out a lot of content... to help explain these things. They can find the article at "Endocrine Reviews." - And I also on my "Instagram" page and... "Twitter" page, or "X," whatever you want to call it, have tried to break down a lot of the key variables in association with this article. And... you can also find the article there as well. So if people want to hear out more, they can check out those places. All right, "Andrew," really enjoyed round two. We're going to link up the research, your social media, everything in the show notes. Thank you. Honor to be here. Thank you for watching. Stick around here for this other great interview. You don't want to miss it. I'll see you over there. There's this multi-year progression of metabolic dysfunction that accumulates over time. Once you actually get the full-fledged diagnosis of something like type 2 diabetes, which is kind of the behemoth in the room that you progress towards when you think about metabolic health, despite... throwing weight loss at