How Long Does It Take To Get “FAT ADAPTED”, Is Insulin Good or Bad, How Many Carbs Do You *Really* Need & More With Dr. Andrew Koutnik.

Ben Greenfield [00:00:00]: My name is Ben Greenfield and on this episode of the Boundless Life podcast.

Dr. Andrew Koutnik [00:00:05]: And we ran these studies and what we saw is that there was no difference once the athletes adapted for four weeks on the ketogenic diet between a high carb diet and a very low carbohydrate ketogenic diet. But here was the kicker. Ben.

Ben Greenfield [00:00:20]: Welcome to the Boundless Life with me, your host, Ben Greenfield. I'm a personal trainer, exercise physiologist and nutritionist. And I'm passionate about helping you discover unparalleled levels of health, health, fitness, longevity, and beyond.

Ben Greenfield [00:00:41]: Hey everybody. Just finished a fantastic discussion with Dr. Andrew Kutnick. We geeked out. If you're into exercise physiology, nutrition, metabolism, high carb, low carb, how long it takes to become fat adapted man, get ready, strap on your propeller hat and there definitely will be a part two for this one. But for part one, go to BenGreenfieldLife.com DrAndrew that's Dr. Andrew. Well, anybody who's listening to this podcast for some time knows that I have a special place in my heart for all things human nutrition and metabolism, particularly as applies to the pointy edges of performance and some of the extreme conditions that my guest on today's show looks into.

Ben Greenfield [00:01:26]: He actually kind of has a career that bridges cutting edge science and elite performance and even personal experience for himself living with type 1 diabetes for quite some time. His name is Dr. Andrew Kutnik. He's got a PhD in medical sciences, molecular pharmacology and physiology from South Florida. He has extensive background in investigating nutrition and metabolism and health and disease and high performance contexts. He has been a part of over 100 different scientific publications and knows a lot about how to get a lot out of the body and the brain, particularly in performance scenarios and also just metabolism in general. So I've been super excited for the past few weeks since this episode got scheduled. So, Andrew, welcome to the show, man.

Dr. Andrew Koutnik [00:02:20]: Hey, it's an absolute honor. Ben, I. I've known you. We didn't even talk about this off here, but I've known you since your bodybuilding days, actually.

Ben Greenfield [00:02:27]: Oh, geez.

Dr. Andrew Koutnik [00:02:28]: I used to. Yeah, I was a teenage teenager attempting to be a bodybuilder at one point in my life. So yeah, I actually know you're that far back, but it's kind of cool to see how far you've come in the world of health and fitness.

Ben Greenfield [00:02:40]: Yeah, that is, that is way back. I don't even remember if I even had a much of a podcast back in those days. So that's funny, I mean, man, you have such a, such unique background. I know with the type 1 diabetes thing that of course is a big, big part of what it is that you focus on, particularly related to blood sugar and ketones etc. But just so people understand going in, because I'm sure it'll come up, how do you describe the difference between type 1 and type 2 diabetes for people who aren't that familiar with the D differentiation?

Dr. Andrew Koutnik [00:03:13]: Yeah, most people who would be listening would think of diabetes as someone who's probably overweight, may not exercise very much, probably doesn't eat the best diet, you know, maybe eats a little too many refined carbohydrates, or could probably have a, a better approach to their nutrition. But that's actually just one form of diabetes. There's actually quite a few. There's type 1 diabetes, type 2 diabetes, there's actually multiple forms of type 3 diabetes that impact people who have genetic disorders, hormonal disorders, insulin binding disorders, and there's also gestational diabetes, which happens during pregnancy. So there's quite a lot of people who have diabetes, but most think of it as type 2, which is a form of diabetes that affects about 90% of all people with diabetes. And this form of diabetes is known best for being what a lot of people believe to be more of a lifestyle based disease, meaning that lifestyle can effectively intervene and help in some cases prevent and also reverse this disease. But it's a disease of insulin resistance. So you do produce insulin, but your body is resistant to the insulin that is produced.

Dr. Andrew Koutnik [00:04:31]: As a result, you have very high levels of insulin in the body, Whereas in type 1 diabetes, as a alternative example, your body no longer has the. It's, it's an absence of insulin. So, you know, for me, around almost 18, actually 19 years ago, I had an autoimmune attack that found the beta cells in the bodies. These cells are the ones that produced insulin and killed them. And as a result, I have been living with no endogenous or internal insulin production. And from that day forward, I have been manually manipulating my metabolism and managing my own metabolism at every single meal of every single day for about two decades. And so the key difference is insulin resistance versus insulin deficiency. And type 1 diabetes is an insulin deficiency.

Ben Greenfield [00:05:27]: How old were you when that happened, that autoimmune attack?

Dr. Andrew Koutnik [00:05:30]: Sixteen, going on 17, actually on a family trip with great irony. And you know, I don't know exactly why I got it actually had lost a bunch of weight. I used to be an obese kid and so hence my interest in bodybuilding, as we were talking about earlier, you know, I wanted to be the polar opposite of what it was growing up, which is obese. I wanted to be, you know, super jacked and strong. But I did have obesity leading into for about six or seven years in childhood, did lose all the weight. But then a year later I get diagnosed with type 1 diabetes. And it appeared that these things had nothing to do with each other. But what I actually came to realize now that I'm a research scientist heavily involved in the exploration of both elite level human performance, but also people living with irreversible chronic diseases like I live with, I've realize that lifestyle actually is one of the strongest risk factors, increasing the risk for autoimmune attacks such as the ones that cause type 1 diabetes.

Dr. Andrew Koutnik [00:06:32]: So obesity certainly is and was a risk factor for me and me potentially getting the disease I have.

Ben Greenfield [00:06:39]: Okay, so you don't think OB or you think obesity was the more likely cause of something like an autoimmune incident versus some kind of extreme lifestyle you were living to get rid of the obesity?

Dr. Andrew Koutnik [00:06:53]: That's a great question because you know, I guess it depends on how you view extreme because what I was doing at the time to lose weight was maybe what most people in the traditional health lane would say is oh, you did everything right, you cut calories, you ate a well balanced diet, you exercised 30 plus minutes per day.

Ben Greenfield [00:07:12]: Right. You took a 20 minute ice bath every day.

Dr. Andrew Koutnik [00:07:17]: Well, even that's a little bit fringe for the general health, wellness or a health community. We're on the wellness trend. Right. But yeah, so we don't actually know even to today, with north of $100 million from the National Institutes of Health dumped into various institutes around the world trying to understand why someone like me gets this disease. We still don't completely understand, but what we do know is that there is an interaction from the environment that triggers an autoimmune attack or interacts with our own genetics to ultimately manifest in an autoimmune attack that kills, kills our own cells. And we know that lifestyle is one of the strongest risks for that. You know, we know that viral infections can be a common risk factor for getting at getting an autoimmune attack. We know that the nutrition you had during adolescence, so whether you were breastfed or not, whether you got vitamin D or enough sunlight, all these things are hypothesis that have been believed to contribute to the incidence of some people being at higher risk for getting a disease like type 1 diabetes.

Dr. Andrew Koutnik [00:08:26]: But one of the most common and prevalent problems we have in society is obesity. You know, that affects over 68% of all adults in the United States today, which is absurdly high number. And I was one of those people in childhood around, you know, actually over two decades ago. So, um, I think that that's probably one of the strongest factors. But I can't negate your point though because I did drink a lot of diet sodas during that weight loss, even though I was doing a whole lot of things correct. You know, for the longest time been, I honestly looked at things like diet sodas. I'm like, oh, whatever, there's no health consequences to things like that. Now there's an emergence of evidence that suggests that the things that are in these drinks like diet sodas, aren't necessarily benign.

Dr. Andrew Koutnik [00:09:15]: There's. There, yes, there are no calories. That's better than having a drink that has, you know, a surplus of 90 grams of rapidly digested carbohydrates. It's going to spike your glucose and insulin. Sure, but it's not better than water, that's for sure. And, and I, I always look back and wonder if my excessive consumption of things that were kind of like sweet replacements at that stage didn't put me at an elevated risk of some sort because I have no genetic history whatsoever to type 1 diabetes.

Ben Greenfield [00:09:49]: Yeah. I used to say, at least from the little bit of data I've seen on something like say acetulfamin potassium, that you'd have to drink something ridiculous like 70 plus cans of diet Coke a day to reach any level of carcinogenicity. But now studies I've seen in the past year have shown data on microbiome disruption, a newer one on anxiety that even seems to affect the genetics in such a manner that it affects the anxiety or stress response of offspring. The more I see it, the farther and farther I space my Diet Cokes apart. And now they're the occasional when I'm going through the airport and that's about it.

Dr. Andrew Koutnik [00:10:37]: Right? Yeah. I think you put it correctly though in that look, we're exposed to many things in life. You could walk outside and you breathe the air and there's going to be maybe pollen in the air or some type of foreign object that you're going to be exposed to. Right. Same thing and what you consume. Right. But it's often, usually volume and load and duration over time that usually predicts whether someone's going to have a long term negative impact. Just like with cigarettes.

Dr. Andrew Koutnik [00:11:04]: No one here is going to promote cigarettes use. But there I think we both Agree that if you go smoke one cigarette, you're not getting lung cancer the next day. It's the accumulated impact of these choices over the lifespan that usually lead to these chronic problems that we see honestly at record levels in society. I mean, but you know, it's pretty, it's pretty solid number to say around 80% or more of America is on the precipice of some chronic disease diagnosis or already has one. You know, if you consider obesity, which the medical community does, a chronic medical disease, then you're at least talking about 70% of America and even children now have diseases like this, such as obesity and prediabetes around 20% today. So, and you know, it's, it's extremely concerning. But one of the biggest triggers that we know of based on that data is certainly the food environment and the food and drinks that adults and kids are consuming.

Ben Greenfield [00:12:03]: Yeah. And I know sweeteners aren't your specific area of expertise per se, and I definitely want to come back to how you're doing some of the extreme things you're doing without producing insulin. But that being said about the sweeteners, do you use like stevia or monk fruit or allulose or have an opinion on any of these ones that are purported to be healthier alternatives?

Dr. Andrew Koutnik [00:12:25]: So yes, we actually have about five or six different publications coming out on this exact topic. So we, but it hasn't come out yet. And so I, you know, listeners can stay tuned to that. I'm a big fan of natural forms of sweeteners that are largely non caloric. So a lot of the chemically synthesized sweeteners, yeah, sure, it's probably better that you consume them than a bucket load of sugar. I, I would contend that's the case. Someone would disagree with me, but I, I would contend that's the case. But we know that things like sucralose, we talked about diet sodas, but sucralose is not uncommon to see in a lot of product ingredients, at least it historically was.

Dr. Andrew Koutnik [00:13:04]: And we know that it doesn't take a lot of it to actually see a consumption that many people in American society would consume, actually inducing in some studies insulin resistance. And so I just generally have found that in my research over the last 15 to 20 years that the further we get away from just kind of natural lifestyle habits, more, more that you're, you increase your risk for problems or issues. And so I'm a big fan of things that may come from like say, plants. So stevia comes from a plant, monk fruit comes from a plant. Allulose comes from a plant you like.

Ben Greenfield [00:13:42]: Like the pure, the pure stevia that they're not adding a bunch of maltodextrin to, which I know some, some manufacturers do.

Dr. Andrew Koutnik [00:13:49]: They do. And the reason they largely have done that in the past is because stevia, when extracted and many of the major forms of chemical extraction do a liquid extraction. And as a result it gets in liquid form. And that's hard to put into a package. Right. That someone could put on the shelf. And as a result, that's why they usually put maltodextrin into stabilizer to keep it into a kind of raw component. But yeah, if you have a packet, let's say Truvia or some other brand, it is almost completely maltodextrin.

Dr. Andrew Koutnik [00:14:18]: But most of the sweetness comes from stevia because stevia's potency is hundreds fold higher in its sweetness per gram than most other sweeteners.

Ben Greenfield [00:14:27]: So much easier to just travel with a liquid bottle of stevia.

Dr. Andrew Koutnik [00:14:31]: Yeah, yeah. Because you can go through airport security with those smaller quantities they sell. But I'm a big fan of stevia. I'm a big fan of monk fruit. But I would also contend that there is a lot of data and you'll see some emergent data come from us as well, showing that allulose, I think is a unique sweetener that actually isn't just a non caloric sweetener, but actually could have some metabolic benefit and the potential to blunt the glucose elevation response to certain foods and also to lower insulin requirements as a response to food. And I think this has a really important impact in the case of diabetes. But a lot of this work has not yet been published. And so but it, you'll, your listeners will see that come out probably over the next 12 months.

Ben Greenfield [00:15:15]: It's my understanding the only real barrier to entry for allulose right now as far as it becoming more prevalent like stevia, monk fruit is from what I understand is a raw ingredients, it's slightly costlier or more costly.

Dr. Andrew Koutnik [00:15:28]: That's a good question. I don't know about the logistics. I do know that it's not necessarily even though it comes from a fruit like it's in figs and other natural food components. And you still have to label it as a carbohydrate, as sugar, even though it's large. Basically for all intents and purposes it's non caloric. And what's interesting about allulose is it's. Many people in your audience have probably heard of fructose, like high fructose corn Syrup and all the negative impacts it has compared to even things like sugar on liver health and obesity and other issues. But what's interesting about allulose is it's actually what they call an E3 Epimer of fructose.

Dr. Andrew Koutnik [00:16:05]: So it actually has a similar chemical structure to fructose, but its chemical structure is slightly changed to where it's largely non digestible and actually has some pretty potent metabolic benefits, not negative effects. But many countries to date, because of their typical slow nature in approving food products in other countries don't see allulose as a natural food ingredient even though it is. And so Canada doesn't see it that way. Many countries outside the United States don't see it that way. And I think that's one of the biggest issues. But I wouldn't be surprised that it also might be a little bit more expensive because typically the more people manufacturing it drive down the cost and it's probably not as prevalent currently.

Ben Greenfield [00:16:49]: Yeah. And interestingly, at least in my experience, unlike the digestion resistant say sugar alcohol like a maltitol or a, or a sorbitol, allulose doesn't really seem to cause like fermentation, bloating, gas type of issues compared to a sugar alcohol.

Dr. Andrew Koutnik [00:17:06]: So I agree with that. Although I think the dose matters. Right. So if someone were to just down a whole canister alulus, they may say something different.

Ben Greenfield [00:17:13]: A dozen keto donuts.

Dr. Andrew Koutnik [00:17:16]: Well, so yeah, I mean I could tell you there if you push. So I've actually done upwards of 80 grams of allulose in a single day and have had no issues. But I will say that there are some people like the data says that around 10 to 20 grams, typically more on the 10 gram side of things, has potential metabolic benefits and response when it's co ingested with things like food. I've actually attested it as someone with type 1 diabetes and it has just consuming alulose by itself and it's actually dropped my blood glucose levels at times 50 to 100 milligrams per deciliter. So there's clearly an impact of allulose. But it appears to be doing Ben is allulose appears to be when ingested triggering the cells within the gut that produce GLP1. Now that most people think of GLP1 through GLP1 receptor agonists like semagnetide, tirzepatide, Ozempic, Wagovi, these type of products, but you produce it endogenously at much smaller volumes. And when it's produced those molecules trigger the reduction of glucagon in the body.

Dr. Andrew Koutnik [00:18:20]: And glucagon causes the constant breakdown of glycogen in the liver into glucose. So he's constantly basically trickling in glucose in the body, but allulose appears to blunt that through a G GOP one to glucagon response. Which is why I also think in the case of type 1 and type 2 diabetes, where glucagon is chronically elevated, you can actually see a hyper response in those conditions.

Ben Greenfield [00:18:44]: Yeah, interesting. It's almost like a. Like a negative glycemic index sweetener.

Dr. Andrew Koutnik [00:18:49]: It is in many respects, it's an interesting thing. I've never heard anyone say that term, but it's actually a really good way to put it.

Ben Greenfield [00:18:57]: Yeah, yeah. So back to the type 1 diabetes thing. So you're not producing any insulin and insulin, my bastardized description, and I know there's all sorts of different takes on insulin, is that it would assist with shoving glucose into tissue so that you can. So that you can be active. If you don't have that at your disposal. I didn't really mention this in your bio, but you're doing things like Brazilian jiu jitsu and extreme endurance training. You're a very active guy. So what's the strategy?

Dr. Andrew Koutnik [00:19:32]: So with type 1 diabetes, the rules are totally different when it comes to managing lifestyle, particularly exercise. So to back up for a second for your audience, to give your audience a better picture, when you have type 1 diabetes, you don't produce insulin, the most powerful hormone the body produces, the most powerful hormone in all of metabolism. When you inject it, you are now overriding and inducing widespread metabolic changes across many tissues and cellular processes. And it's dose dependent. So you now control all the power of that molecule. And in the context of type 1 diabetes, we, unlike any other disease to date, you actually, number one, manually administer it and have total control over when you administer it. But number two, know the exact amount and dose by which you're administering at different times. So you can at all times track, unlike any other condition, any, unlike any other advanced laboratory in metabolism.

Dr. Andrew Koutnik [00:20:31]: Because I work with them and I still work with them. You can track metabolism and the impact of insulin in type 1 diabetes greater than in. In any other environment. So you have total control over insulin. But it comes at a price. It's also extremely dangerous. Many bodybuilders have injected insulin because of its anabolic properties and also died as a result of it. So there is a fatal potential when overdosing a molecule like insulin.

Dr. Andrew Koutnik [00:20:58]: There's Also, pretty profound negative implications to your physical well being and mental well being if you underdose at, let's say, any particular meal and your blood glucose runs high. And so it's a really tight game of trying to manage a number of key factors, but you have more control over your metabolism and gain more insights compared to any other environment or condition that I know of in science or in disease or in health. That said, when it comes to managing type 1 diabetes, you have to simplify it down. There is extreme nuance. There's over 40 different lifestyle factors that affect insulin sensitivity and absorption. As a result, all these lifestyle factors that people talk about in the health space, okay, getting sunlight, heat exposure, cold exposure, various medications, poor sleep. We have known for decades and sometimes centuries that those factors affect insulin sensitivity and also sometimes the release or absorption of glucose. And so when it comes to type 1 diabetes, I usually simplify it down and keep it more relevant to your general audience here as glucose and insulin, These are the two most important molecules in metabolism, the two most important molecules that regulate type 1 diabetes.

Dr. Andrew Koutnik [00:22:21]: Glucose levels are kept in this very tight range of 70-120mg per deciliter. And that tight range for people without disease is where most people spend their life. When you start developing diseases like diabetes, you start living above that range for higher and higher percentages of time, and it leads to accumulated impacts, negative impacts on various tissues. But there's a glucose focus. Well, glucose is the number one predictor of outcomes in type 1 diabetes. Not only every single meal, but over your lifespan, over the duration of this disease. Now, what's the number one factor that affects glucose? Well, food, but particularly carbohydrates. So there's a keen focus and interest around carbohydrates.

Dr. Andrew Koutnik [00:23:06]: Not only type, but also more importantly, quantity of carbohydrates that are consumed. But we also know that more glucose that enters the bloodstream requires more insulin. So carbohydrates not only directly impact glucose more than any other lifestyle factor does, but they also directly impact the quantity of insulin. Now, that brings a central focus to nutrition. Nutrition is the most potent factor in regulating glucose and insulin, the two most important markers in D type 1 diabetes management and also in all forms of diabetes management. But exercise, to your question, directly influences not only glucose, but more importantly, insulin absorption and sensitivity. So when someone has diabetes, they often have, particularly type 1 diabetes, where you have control over insulin, you have to be particularly vigilant. You almost immediately become a world expert in metabolism.

Ben Greenfield [00:24:08]: I know where you're going here, the same level of insulin is going to have a remarkably different effect if you've say, exercise versus been sedentary, for example.

Dr. Andrew Koutnik [00:24:17]: Absolutely, Ben. So all the data that we've heard about of, oh, resistant exercise improves your insulin sensitivity or hey, aerobic exercise for exhaustion, not only reduces your insulin, but maybe increases insulin independent glucose uptake. Like all these things you hear about. This is the lived experience of someone with type 1 diabetes. And it's a tightrope of every single day micromanaging all these variables to try to keep tight control in glucose. And so that is in essence, type 1 diabetes, the lived experience of type 1 diabetes.

Ben Greenfield [00:24:49]: Okay, so possibly a stupid question here. I wear a glucose monitor not because I have diabetes, just sheer curiosity. And what gets measured gets managed. Right. Less likely to candy bar in an airplane. But in your case, theoretically, couldn't you track your blood glucose and, and have some type of real time feedback go to say, like an automated insulin delivery mechanism and be able to have interplay between the two and in a pretty precise manner?

Dr. Andrew Koutnik [00:25:21]: So that is exactly what we utilize as the primary tools from a technology standpoint to regulate.

Ben Greenfield [00:25:29]: I was hoping I was the first person that thought of this and I was about to make a lot of money.

Dr. Andrew Koutnik [00:25:33]: Well, you know, we can just. Okay, I'll pretend like it didn't happen, Ben, you'll know we've never heard of that. It's amazing. Brilliant idea.

Ben Greenfield [00:25:39]: All right. I just invented this new thing.

Dr. Andrew Koutnik [00:25:41]: Yeah. So there's actually the gold standard Technology in type 1 diabetes today is utilizing a continuous glucose monitor. And by the way, the use of continuous glucose monitors are incredibly valuable tools outside of diabetes, regardless of how much anyone tells you they are, they are. They're incredibly valuable tools. But they started in type 1 diabetes first. In fact, the first continuous glucose monitor was developed for the use of type 1 diabetes. But they were then refined multiple times over, and then they became accessible to people with type 2 diabetes and then the general population as well. And so a lot of times things start here with type 1 diabetes when it comes to metabolism.

Dr. Andrew Koutnik [00:26:16]: But most people with type 1 diabetes have a continuous glucose monitor because it tracks the most important metric in your management of your disease and how you feel of every single meal of every single day, continuously, minute by minute, 24, 7. Now, on the other end of things, you also have people who either inject insulin or on the back of my arm here is an insulin pod which essentially holds insulin and releases that insulin into my tissue. In this case, it sits usually on the skin and Releases it into the, what they call interstitial fluid, the fluid that sits between your cells, like let's say, fat cells and muscle cells. It sits in between these cells and that is where the insulin is deposited with type 1 diabetes. Now there are technologies, Ben, that actually integrate, using computer algorithms in the interaction between the continuous glucose monitor, glucose readings, but also insulin administration, and they're called automatic insulin delivery systems. They, they're basically the AI technology and medical management for glucose and insulin and type 1 diabetes. Here's one major caveat to these tools though, Ben. While they are remarkable tools, they do very little in actually improving glucose control.

Dr. Andrew Koutnik [00:27:36]: And someone may wonder, how is that the case? If you're able to completely override and have computers control everything when it comes to insulin and glucose management, why doesn't it work basically perfectly and guide you into normal glucose control with type 1 diabetes? Here's the kicker. When you inject insulin from outside the body, it is three to four times slower than the insulin that's produced within the body. As a result, it doesn't have its peak insulin response until 60 to 90 minutes later.

Ben Greenfield [00:28:10]: Is it slower because it's in the interstitial fluid initially, or is it slower because it's actually a different molecule than what would be endogenously produced?

Dr. Andrew Koutnik [00:28:19]: It is because of the tissue it's injected into. So in your case, Ben. So let's say Ben's decides, you know what, I'm going to eat a box of donuts, okay? So he's sitting here, he's walking on a treadmill right now, but you know, he's like, I'm going to eat a whole box of donuts. So he starts downing them back. The second those donuts in his gut start being digested from these, with these, these chains of glucose molecules into individual glucose molecules, they're going to be absorbed into the body. Once they're absorbed into the body, those glucose molecules are first, first going to go into our, what they call first pass, first mass metabolome, or they're going to go to the liver first, then they're going to go through the bloodstream in the pancreas. The second that the pancreas, particularly the beta cells, the ones that I don't produce as someone with type 1 diabetes, are going to sense the elevation in glucose and instantly they will start releasing insulin that is already made, already manufactured in these pre stored, almost bubbles that these bubbles essentially pop open and release the insulin directly into the bloodstream, the central bloodstream. Why is that important? Because when it's Released into central bloodstream, it goes directly to the liver.

Dr. Andrew Koutnik [00:29:44]: And that's where you start having resynthesis of glycogen in the liver. All about 3, 4, an estimated around 66% to 75% of all the glucose and insulin the body originally sees in a normal environment without diabetes. And insulin from outside the body is going to go to the liver first and be stored as glycogen, Only about a fourth to maybe a third is actually going to get to the peripheral tissues like the muscle and fat tissues. This is where things get interesting. With type 1 diabetes, you flip that equation. With type 1 diabetes, when you inject insulin in the exterior tissue, it has to absorb from the external interstitial fluid into the bloodstream, then go through circulation. And actually about 66 to 75% of that insulin is now going to go direct to the fat tissue. But also, which could be a sports performance advantage if you know what you're doing, the muscle tissue.

Dr. Andrew Koutnik [00:30:44]: So when you inject insulin from outside the body, you actually disproportionately bind these tissues, such as the muscle tissue, at around 3 to 4 higher levels. Whereas when someone just endogenously eats or eats carbohydrates or various foods, and insulin's elevated, most of that is actually going to be stored in the liver first. And so in this way, this is a unique, not paradox, but almost flip of the coin when it comes to how insulin works in type 1 diabetes, depending on where you're administering it, much less about the type of insulin, you.

Ben Greenfield [00:31:23]: Know, and I don't really have any interest in doing this, but I find it intriguing. You know, you said if you know what you're doing, it could increase sports performance. And you referenced earlier the, the anabolic potential of insulin when used correctly. And it sounds like some bodybuilders are doing that. How effective are we talking when it comes to improving? And I'm assuming you mean muscle hypertrophy or muscle recovery or something like that. If. When we're actually injecting insulin as some kind of ergogenic aid.

Dr. Andrew Koutnik [00:31:54]: That's a really great question. There's actually very little research on the implications of exogenous insulin when it comes to sports performance. Performance or metrics related to sports performance. But let me back up for a second on that, because there's plenty of evidence that tells us what should happen as a result of how we know insulin injected outside the body versus insulin produced inside the body should work. One key example of that is, of course, how much higher it binds, as we spoke about, to Fat and muscle tissue. So when bodybuilders are utilizing insulin, they have to be, I'm not telling them what to do, I think this is a very dangerous practice. But they have to be very careful because insulin is much more anabolic to fat tissue than it is to muscle tissue. Much more anabolic.

Dr. Andrew Koutnik [00:32:42]: And so as a result, when people inject exogenous insulin hoping for this muscle benefit, yes, there is a muscle benefit, but you gotta be careful because it's also potently anabolic to the fat tissue. As we know, in the case of obesity and type 2 diabetes, insulin is much higher. As a result, you also see much higher fat storage. So in the context of type 1 diabetes, when we think about, in the injection of insulin, you will see more insulin at the muscle tissue. And when you do, that means that most of the insulin that you injected isn't going to just store it into liver, it's going to tissues that work for performance, particularly the muscle tissue. And to give you a stark and extreme example, you can force this during environments where it normally physiologically wouldn't happen. No, these are, let me make clear, this is not recommendations, I'm just telling you the physiology here. So there are reported cases of, let's say, ultramarathon athletes with type 1 diabetes who at the end of an ultramarathon gained eight pounds because of the ingestion of glucose, but also the administration of exogenous insulin to control the exogenous glucose they consume.

Dr. Andrew Koutnik [00:34:01]: Whereas in a normal older man marathon, you would not be gaining weight, you would be losing a lot of weight. So it's a stark contrast of what can happen when you have total control over insulin.

Ben Greenfield [00:34:13]: Yeah, and it was a weight gain because they were simultaneous, like burning glycogen, but then also massively storing glycogen.

Dr. Andrew Koutnik [00:34:21]: So when people think about performing in sports, there's the sports nutrition guidelines say that people should be consuming 60 to 100, well around 60 plus grams of carbohydrates per hour. And if you exercise like one of these elite level athletes, you know, upwards of four plus hours per day, you should be consuming five to 12 grams per kilogram per day, which for an average body weight male. So like Ben, if you were to be meeting those guidelines and you did the upper end, you'd be consuming over a thousand grams of carbohydrates per day.

Ben Greenfield [00:34:51]: Yeah, I was gonna say, like even a low end day, I'd be at 800 grams. So like 3200 calories worth of carbohydrate alone.

Dr. Andrew Koutnik [00:34:59]: A lot Quite a lot. And that is the, that's the, that's the gold standard recommendation from most sports nutrition guidelines. So as a result, when people think about fueling for performance, they think just like people with, with, with diseases or not, they think I need to follow these guidelines. Yeah.

Ben Greenfield [00:35:18]: And it's really good business for Gatorade and the bakery case at the local coffee shop on the cycling trail. Right?

Dr. Andrew Koutnik [00:35:24]: Yes, of course. I mean, absolutely. I mean, it certainly doesn't hurt the gel companies and other sports drink companies. But here's a little bit of a caveat to this, is that when you have type 1 diabetes and you're ingesting that glucose, you have to take insulin for it and that insulin is going to now store that as not only does insulin, when in the bloodstream, pull in glucose into fat tissue, into muscle tissue for storage and then use, but it also pulls in water and sodium. So you're pulling a tremendous amount of water weight into these tissues as well. Like if you're running an ultramarathon, last thing you want to do is gain eight pounds while running, you know, the longest race of your entire life. Right. That's not, that's not a good choice.

Dr. Andrew Koutnik [00:36:12]: You're going to be carrying around eight extra pounds unnecessarily.

Ben Greenfield [00:36:15]: Right. A little bit of a balancing act. Of course. You know, I don't even know where glycerol now stands on the WADA band list or on global dro, but there was a time when endurance athletes would hyperhydrate using glycerol and actually like a camel, carry a little bit of extra water weight. I don't think it was anywhere near £8. But, you know, some have hypothesized this strategy of carrying a little bit of extra water on board maybe beneficial, you know, in long, potentially dehydrating events.

Dr. Andrew Koutnik [00:36:43]: So that's a good point. But there's also evidence that mild dehydration makes people perform better in body weight based exercise.

Ben Greenfield [00:36:50]: Yeah, yeah. You look at the top finishing times of all the marathoners, Right. And they're, you know, they're not the hyponatremic ones at the back of the pack. They're like whatever, like 3% dehydrated at the finish line or more.

Dr. Andrew Koutnik [00:37:00]: Yes. And that's, it's not uncommon to see that because there are some consequences to over hydrating not through glycerol per se, but actually through over consumption of water without appropriate minerals alongside it. But that said, we've actually done a number of trials looking at the implications of various diets, specifically the ones that are commonly recommended, which are high carbohydrate diets, and directly comparing them to very low carbohydrates, specifically ketogenic diets as a stark contrast, because we know the ketogenic diets, you have much less glucose consumption.

Ben Greenfield [00:37:33]: Wait, I got, I gotta ask you before you jump into this. Are you talking about like in a performance scenario?

Dr. Andrew Koutnik [00:37:38]: Yes.

Ben Greenfield [00:37:39]: Okay. Okay, this is interesting.

Dr. Andrew Koutnik [00:37:41]: So we've done studies getting, we had experienced runners, minimum requirements, you know, we're not talking about elite here, but very experienced runners who are actually competing in races. The minimum is at least, they're running at least 50 kilometers per week. They, their VO2 max had specific minimums, um, and their body weight was very low. They were very fit athletes. And what we asked them to do is we said, hey, sports nutrition guidelines say that you need to consume these high volumes of carbohydrates. But let's pause for a second. The rates of metabolic dysfunction in America are reaching unprecedented levels, even in athletes, by the way, fit athletes at that. And what.

Dr. Andrew Koutnik [00:38:22]: And we know there's these powerful therapeutic potentials of diets like the ketogenic diet, but many people won't even try these diets because of their concern around the hypothesis that not consuming enough carbohydrates will impair performance. And so we asked the question, what if we conducted studies where we asked athletes, legit athletes, to not only do a high carbohydrate diet, but then switch to a very low carbohydrate ketogenic diet for at least four weeks in duration? That is extremely important, Ben, because a lot of prior studies have shown minority impairments in performance around 2%. You know, the average weekend warrior never know the difference, but elite level athletes, first and second place is less than 2% almost always. And so when we think about performance in the context of, of ketogenic diets, we wanted to allow the body to fully adapt to the diet effects. And we know that there was literature dating back to the 1960s and 70s that when you induced very low carbohydrate intake that it could take over three weeks to see normalization of things like glucose free fatty acids, ketones. There's these conic changes that are occurring over time that we've known for almost a century. But all these people were running studies saying, well, hold on, we see ketones elevate, we see insulin go down, we see whole body oxidation changes and reductions in carbohydrates being utilized during exercise, dramatic increases in fats being oxidized during exercise, even within the first five days to two weeks. And the answer is sure that is true, particularly in athletes.

Dr. Andrew Koutnik [00:40:07]: But there are changes that happen within the kidneys, changes that happen with other tissue systems, particularly normalizations of key metabolites within the body that regulate performance that don't normalize reliably for at least four weeks. So we asked them, we want you to, to do these diets for at least four weeks in a randomized fashion. We also controlled their body weight, Ben, we controlled their physical activity, their calories. We did everything to control variables that commonly are not controlled in exercise performance studies, but they directly impact the outcome. Because we really wanted to explicitly answer the question, Ben. If you shift around the macronutrients in your diet, particularly from a high carbohydrate diet, which is recommended for sports performance, to a very low carbohydrate diet, which people hypothesize will impair performance, but we allow the body to adapt and we control the key variables, what happens. And we did this in two different key studies. The first study was in very short duration, high intensity, 1 mile max effort time trial.

Dr. Andrew Koutnik [00:41:12]: We also did 6 by 800 meter sprints because we really wanted to look at these two very highly intense energy system perform or forms of performance that usually are highly dependent on carbohydrates.

Ben Greenfield [00:41:27]: Right, what we call like glycolytic or even, even carbohydrate depleting type of activity.

Dr. Andrew Koutnik [00:41:34]: Yes, exactly, Ben. Because in theory, if these are highly dependent on carbohydrates and you consume a diet deplete of carbohydrates, you should in theory see a deterioration in performance in those specific exercise bouts. And we ran these studies and what we saw is that there was no difference once the athletes adapted for four weeks on the ketogenic diet between a high carb diet and a very low carbohydrate ketogenic diet. But here was the kicker, Ben, that really blew my mind. As someone who lives with a chronic metabolic disease, we actually track the glucose levels in these athletes, not at a single time point like HbA1C or fasting glucose levels, but over every minute of every day, over weeks and weeks. And what we found is that 30% of these fit athletes, high VO2 maxes, exercising over 50 kilometers per week and running at a minimum, had glucose levels consistent with pre diabetes. And this was a total shocker to me because 30% of these athletes presented with this. This shocked me because I had never seen this before.

Dr. Andrew Koutnik [00:42:46]: And when we published these results, I actually Had a number of athletes as well as clinicians reach out to me and say, hey, that actually happened to me and I don't understand what's happening. But I just wanted to let you know you're the first people to ever show this was happening. And that shocked me because what we also showed in the study, Ben, is that when the athletes went on the very low carbohydrate ketogenic diet, not only did they have the same performance, they had no deterioration in performance, but 100% of the athletes improved their glycemic control. There was no signs of prediabetes in any of the athletes anymore. Completely resolved this instantly, Ben. It wasn't like over multiple weeks. Almost upon the first initiation of the diet, it was resolved. So, and that was a shocker because now it changed the conversation around.

Dr. Andrew Koutnik [00:43:32]: Well, if you can do this diet and maintain performance, particularly on short duration, high intensity, maybe it's a conversation about performance, about health. And one thing that arose out of this is, well, how, how is it possible that someone is fueling this very high form of ex. High intense form of exercise on an exercise bout that is almost exclusively glycolytic? I mean, There are over 85% of their VO2 max the entire time, which based on our understand understanding of sports nutrition and exercise physiology, would estimate that less than 10% of all energy would be coming from fat.

Ben Greenfield [00:44:10]: Right. And, and, and, and you should have a banana, bro.

Dr. Andrew Koutnik [00:44:13]: Exactly. You should be having a banana. You should be downing the carbohydrates. Because you quote, unquote, I put quotes around this, require carbohydrates for this exercise bout. But what we found is that these extremely high intense form of exercise, when athletes actually adapted for long enough, even in athletic endeavors that are extremely glycolytic, where almost no fat should in theory be able to be utilized as a fuel substrate. We found that over 50% of the total fuel was coming from car, coming from fat at record levels. We actually reported the highest ever levels of fat oxidation in the literature in this report. And it, it goes to show that this hypothesis that carbohydrates were required for exercise, and yet very high intense forms of exercise does not hold weight.

Dr. Andrew Koutnik [00:45:02]: We see that you can actually perform even at 85% of your VO2 max, extremely high levels of fat can be utilized to fuel that exercise. Now many people saw that performance study and thought, okay, that's interesting, but it's short duration. There's no way that athletes were able to do very long duration forms of exercise where the amount of Carbohydrates being oxidized play a quote, unquote critical role in your overall speed and performance. The amount of glycogen that you store would be extremely important for that performance bout. And so we then tested a different form of exercise. We then recruited Ironman competitors, people who are actively competing and had completed an Ironman. And, and we asked these athletes to do the exact opposite. We asked them to go as long as they could at 70, 70% of their VO2 max, a prolonged, strenuous form of exercise until they, quote, unquote, hit the wall.

Dr. Andrew Koutnik [00:46:04]: But we asked them to do it not just on a high carb diet, but also on a very low carbohydrate ketogenic diet. And we allowed them to adapt for, again, at least four weeks, controlling all these key variables. And again, Ben, what we found was that in these athletes they were able to not only perform identically to high carbohydrate based diets, but then we found that when we just trickled in enough glucose, Ben, not enough glucose to change the amount of glycogen in the muscle, not enough glucose to change the amount of carbohydrates that are utilized during exercise, but just enough to maintain blood glucose levels because it requires so much less. So 1 tablespoon every hour, equivalent to 10 grams per hour, or 6 to 12 times lower than gold standard fueling recommendations for carbohydrates based on sports nutrition guidelines. And what we found is that just that little bit of trickling it in was able to not only maintain blood glucose levels, completely eliminate hypoglycemia, which we did see without it, and improve performance on both a high carb diet and a very low carbohydrate ketogenic diet, 22%, illustrating that one of the key determinants of exercise performance does not appear to be carbohydrate oxidation levels, does not appear to be the level of glycogen it appears to be more consistently than any other biomarker, the control and regulation of glucose levels in the blood. And what that shows, Ben, is something extremely critical. We just got accepted the largest review ever conducted over a hundred years of data, over 600 citations, multiple meta analysis in the same report and endocrine reviews. And what this report shows is that when we reviewed all the exercise performance studies where carbohydrates, quote, unquote, improve performance over 80% of those trials, I think the exact number is 88%, the placebo group had a drop in blood glucose levels, which means that the reason primary Reason that's more consistent across the literature of all published data over a hundred years of why someone is improving performance with any volume of carbohydrates appears to be primarily the regulation of blood glucose levels, not inherently carbohydrate oxidation levels, muscle glycogen, et cetera.

Ben Greenfield [00:48:33]: Yeah, yeah, this, this reminds me of some of the studies, multiple studies that you're no doubt familiar with, of the swishing glucose in the mouth response and the fact that that reduces rating of perceived exertion or improves performance despite someone not actually consuming carbohydrates with. From what I understand, the prevailing hypothesis being that you have this central governor that would limit your ability to reach certain levels of performance if it suspects that blood glucose is going low. Therefore, the mere taste of a glucose substance or the small amount of absorption that occurs in the salivary environment might actually improve performance. You and I didn't talk at all before this podcast about this research, but I don't know if you're aware of this. I was part of the Volek study on endurance athletes in which we followed a pretty low carb, very low carb, almost 85% fat based ketogenic diet for, in my case, 12 months leading up to an endurance and a VO2 max trial, and had results very similar to what you've described in terms of rewriting the textbooks on how much fat can you oxidize during exercise and how many carbohydrates do you really, or not really need. But I do have some clarifying questions for you that I'm super curious about. So teacher, I have questions with these studies that you did. You know, people talk about becoming a fat burning machine and like you alluded to Andrew, having a certain number of weeks or even months before you reach the full ability to be able to really burn carbon or burn fats efficiently.

Ben Greenfield [00:50:10]: Did you guys look into or have you come across anything in terms of like dose response, of time, like how long it takes before the results really start to kick in significantly in terms of weeks or months?

Dr. Andrew Koutnik [00:50:23]: We didn't do it on purpose, we did it on accident. What we found was that when we actually were tracking key metabolites over using continuous glucose monitoring, actually doing plasma levels or, sorry, capillary levels, blood ketone levels, what we found is that the level of key metabolites in the blood related to fuel, particularly glucose and ketones, that they appeared to peak and then normalize after the three week mark. So we found that ketone levels actually peaked right out to the three week mark and stabilized and Reached homeostasis. We also found that glucose levels initially drop even in healthy individuals who have no chronic disease, but then they come back up to normal baseline at the four week window. So we actually did find key metabolites that had not been previously discovered to actually show that alongside the performance normalization effect, we also were seeing a normalization and plateau of metabolic homeostasis through metrics of ketone normalization and also blood glucose normalization through continuous glucose monitoring.

Ben Greenfield [00:51:34]: Okay, super interesting. So it just speaks to the remarkable metabolic plasticity of the human body. Somebody could probably grow up on Cheerios and donuts and whatever and within three to four weeks experience those metabolic adaptations with a macronutrient adjustment. Okay, so that's super interesting. How about in terms of the hypotheses about why, especially in the more glycolytic events, the people eating the high fat diet were able to still have stable blood sugar? Was it more a situation which they were depleting their glycogen reserves less rapidly because they were able to burn fats more efficiently? You know, some kind of like a glycogen conservation mechanism? Or was it more something related to like, I don't know, insulin sensitivity or some other factor that allowed them to maintain stable blood glucose values?

Dr. Andrew Koutnik [00:52:30]: You're asking all the right questions. What we found, and no one's asking these questions, by the way, ironically, we don't, I don't often get this question asked, but this is actually a super important question that leads to something that we recently discovered, which is that when you think about the impact of what actually regulated exercise, what we found is that while the ketogenic diet group had the same level of performance, and by the way, these are the same people. Like they crossed over, they did both diets. So we were controlling environment and genetic factors, the same person. What we found was that on the very low carbide ketogenic diet arm, there was a higher incidence of hypoglycemia or lower blood glucose levels, but yet they had the same level of performance. So then what I did, Ben, is I then calculated the total amount of brain energy fuel in the blood. Now keep in mind, glucose, we have known this since the 1960s, is not the only fuel for the brain. We know that things like ketones are also fuel for the brain.

Dr. Andrew Koutnik [00:53:35]: More recently, over the last couple decades, we've also know that lactate is a fuel for the brain. And, and, and it's also important for your listeners to appreciate that lactate and ketones are used at higher preference in a dose Response to how available they are to the tissue, meaning their levels in the blood, whereas glucose is utilized only proportional to the energetic demand of the tissues themselves. So what I did is I calculated, okay, we have these two groups, they had the same performance, but yet one had higher levels of hypoglycemia. I'm going to now calculate the total brain energy metabolites that were present in both groups because we know that when you have lower glucose on a ketogenic diet, you also have higher ketone levels. So I calculate the total net brain energy metabolite calories between both diets. And what we found is that the ketones and lactate, which were much higher in the ketogenic diet arm, but the glucose was lower, actually had equivalent levels of brain energy substrates as the high carbohydrate diet arm. And this totally aligns with our major review that came out, looking over a hundred years of evidence showing that performance begins in the brain. If you don't have sufficient brain energy metabolites, you will not perform well physically.

Dr. Andrew Koutnik [00:55:00]: You know, no greater example, chop the head off, you don't perform well. You know, that's extreme example, obviously, right? But you need your brain to perform well. Just like you use the example of carbohydrates swishing, the anticipatory effect, the positive relationship with carbohydrates in the brain. This dopamine response has been largely levied to believe to be why it's improving performance, not because it had a metabolic benefit per se. And so that's important to realize. But we also know these molecules, such as ketone bodies, have very unique metabolic effects that extends far beyond just their ability to fuel the brain around physical performance. In this case, they also have a wide sweeping impact in other areas as well, which we've done a lot of research on to date.

Ben Greenfield [00:55:50]: Super interesting. Okay, couple more questions. I know we're getting close to time here and we are going to have to have a part two, by the way, because I've asked you a third of the questions I wanted to ask you. Okay, so you, I don't know if you were choosing your words carefully, but you said that you saw better glycemic control in the low carbohydrate group. One thing that I've seen, and I don't recall if I've seen this in literature or if it's more of a hypothesis in the nutrition science and metabolic community, is that when somebody shifts to a low carb diet, even though glycemic variability can stabilize or like how much Your blood sugar is going up and down. During any given day, the average blood glucose might slightly rise due to a greater amount of glycogenolysis occurring, freeing up endogenous glycogen stores to keep glucose a little bit more elevated because there's less coming in exogenously. So I guess what I'm wondering is, did these people have better glycemic control, lower glycemic variability and lower the same or higher average blood glucose?

Dr. Andrew Koutnik [00:57:02]: Great question. They had lower blood glucose on the average, lower variability on the. And by the way, every single person had lower blood glucose levels. Every single person had lower variability. It wasn't a average response, it was every single person had this response. But I want to address your point because you brought up a very important point that is controversial in the ketogenic diet world, which is. Well, there's this, you know, we always think about rising glucose levels as this terrifying thing that has negative consequences is. And in the general sense that's true.

Dr. Andrew Koutnik [00:57:32]: There's a clear dose response that as glucose levels are reliably getting higher and higher on average over 24, 7 periods of time, over weeks, months and years, they have clear negative implications on your cells, your tissues, and lead to complications of the eyes, the kidneys, the, the cardiovascular disease. A whole bunch of different array of complications long term. But we also know that when in the normal range, these risk factors are almost completely non existent. Right. So if someone were to have normal glucose and they move down in glucose, even into slightly more normal glucose, one could contend there's no meaningful difference here. Now, some would argue there's a meaningful difference. There might be an optimal level of glucose, but when we think about even within the normal range. So let's say your average glucose is still in the normal range, but may not be optimal, that's a totally different thing to unwrap.

Dr. Andrew Koutnik [00:58:35]: But I wanted to get direct to your question. Your question is more around the conversation around the ketogenic diet, this very low carbohydrate diet, that while you might see lower variability, your average glucose may rise slightly. That only happens, Ben, if someone is a normal healthy individual who is typically free of disease. Because when someone initiates a ketogenic diet and the, the glucose load that they're consuming is usually five fold lower, the amount of insulin that they're now producing. Or let's say in the case of type 1 obese, having to inject goes down upwards of sometimes, you know, 60, 60, 75%. These are all remarkable positive changes. But it depends on where you start, if you start at a normal blood glucose level and you go on a ketogenic diet, yes, you see less variability. But you start utilizing other fuel substrates at higher proportions like fat, like ketone bodies, and so your reliance on glucose is also lower.

Dr. Andrew Koutnik [00:59:30]: And as a result, people often talk about, well hold on, if I take glucose, then glucose goes higher. Well, you're utilizing a more diverse array of nutrients at higher proportions. Now as an example, we know that a lot of our studies, we have found that when you're on a ketogenic diet, the volume of fat that's making up the calories burned during exercise is around 55% where it's carbs is 45%. Whereas on the high carbohydrate diet arm, the proportion of carbohydrates being burned is infinitely higher. So you actually appear to be more metabolically flexible. If you, if you think about it from a core quantifiable biomarker standpoint of how much of each carbs and fat are using, it's more equivalent on these ketogenic diet studies or ketogenic diets than it is with higher carbohydrate diets. But we do see in some cases where very lean healthy individuals who already have normal glucose control go on the ketogenic diet, they typically have a lowering of glucose.

Ben Greenfield [01:00:27]: I'm raising my hand. If I eat 30 to 40% carb based diet, I hang around in the 85s ish for blood glucose. If I go keto low carb, especially once I start to drop below about 20% and who knows, maybe part of this is like a hypercortisolic response, I tend to be closer to the 95s.

Dr. Andrew Koutnik [01:00:50]: And that this is fascinating stuff. So for your audience who this is getting the nitty gritty. So in your case, Ben, you're still in the normal range. Actually, if you look at continuous glucose monitors for the average healthy individual with no form of chronic disease as, as a biomarker, a lot of people talk about fasting glucose levels or HbA1c. That's a completely different measurement than interstitial glucose values coming from continuous glucose monitors. So if we focus on the actual continuous glucose monitor interstitial value that is associated with health, that number actually is between 90 and 100 milligrams per deciliter. And yes, it may be true that lower is better. That absolutely might be true, but it's still in the normal range.

Dr. Andrew Koutnik [01:01:32]: But the fact that it's creeping higher is likely explained, Ben, because when you get on a ketogenic Diet across the literature, across how we know physiology works, you see this flip of glucose based metabolism towards a more predominant fat based metabolism that doesn't reliably happen until carbohydrates get low enough. That's extremely important for people to realize because they may say, oh, I reduced my carbohydrates. I didn't see all these effects that all these studies show that a ketogenic diet can do. A ketogenic diet is defined not only by the amount of carbohydrates, but also the physiologic elevation of ketone bodies which only reliably elevate when insulin is sufficiently low. This is how this diet is distinct from, from all these other forms of just carbohydrate modulated forms of diets. When you get into a ketogenic diet, you only actually get there by inducing a clear change in physiology induced by a reduction of insulin below a specific threshold. Before that, you have no guarantee of any metabolic benefit. And that's why that is a distinct metabolic state that is objectively defined versus just lowering carbohydrates in the diet.

Ben Greenfield [01:02:49]: Yeah, it's so interesting. Okay. But I mean, honestly, we're also kind of like grasping at straws a little bit because both are 85 and 95 are both somewhat within range. I just think it's an interesting relic. Okay, last question, at least for this round. The group, especially the Ironman group, following the low carb diet, did you guys track anything related to endocrine function or other organ systems, particularly thyroid and testosterone, the two that I see most often referred to as something that might be deleteriously affected by combining a ketogenic very low carb diet with high amounts of exercise.

Dr. Andrew Koutnik [01:03:40]: So when people talk about those effects, I actually looked into the literature on these effects, things like thyroid function, the hypothesis and change on various other tissue systems that may be seen as negative related to the ketogenic diet. And so to answer your question, first, we did not look at these in the ironman athletes. However, in the prior study we did look at cardiometabolic effects like insulin glucose levels in various other cardiometabolic biomarkers and we saw the typical changes we would expect on the ketogenic diet. However, I actually, our group has published the longest ever longitudinal report of a ketogenic diet in history. 10 years in duration. And longitudinal meaning, what's important about longitudinal means we didn't just ask someone, hey, have you been on a ketogenic diet for 10 years? We're going to study you at one time point we actually had data over a 10 year period on someone with a chronic metabolic disease and type 1 diabetes over a 10 year period, having followed a, you know, the American Diabetes Association, Whole Foods higher carbohydrate based approach and then switched over a 10 year period while controlling their weight, their calories, their physical activity to see the long term implications over a ten year window of the ketogenic diet, not only on things like glucose control and insulin, which improved dramatically and insulin reduced 43%, but also on thyroid function, kidney function, liver function, bone health, something that people talk about because of these short term studies showing deterioration and biomarkers of bone health. What we saw in this study, the longest report ever of the ketogenic diet with longitudinal data, was that there was no deterioration in thyroid function. In fact, when I reviewed the literature on thyroid function, there isn't consistent data saying that people will reliably see deterioration Thyroid health.

Dr. Andrew Koutnik [01:05:38]: That is something that has come up as a result of the general Internet community about hypothesis about these changes. And for some people that's certainly the case. But you have to be careful because often when someone goes on a ketogenic diet, they also calorically restrict inadvertently and when you caloric restrictions, you will change thyroid biomarkers.

Ben Greenfield [01:05:58]: Yeah, and there's also just like so many other factors, like did you increase your intake of goitrogenic vegetables? Did you all of a sudden get healthy and start swimming in a chlorinated swimming pool every day? Like, like there's a lot of variables that could affect just the thyroid alone that people might mistake for the macronutrient adjustment that could be attributed to something else.

Dr. Andrew Koutnik [01:06:18]: You nailed it. And this is why it's so important to understand what's happening and also to test it on yourself. Right? You know, here's the thing, is that a lot of people were like, well why would I even consider doing such a thing? Or an athlete may wonder, okay, I've heard you just talk about this, you know, but I perform fine. I say that's awesome, that's great. There's no need to change unless you want to. But sometimes you never know the effect that some intervention may have on me unless you try. What if you were to got better and you would have never known even if the studies, even if I tell you here, Ben. Hey, Ben.

Dr. Andrew Koutnik [01:06:49]: We did the longest reported study ever conducted on ketogenic over 10 year period. We looked at the cardiovascular health. We saw no deterioration in cardiovascular health, we saw no deterioration in bone health, no deterioration in thyroid health, liver function, kidney Health, none of them, no adverse effects whatsoever. In fact, an apparent dramatic overall cardiovascular function that was better than those people of similar age, sex, even without chronic disease. But I could say all that, Ben, but also tell you that what if you tried it by yourself? What if you tried it and you didn't have a good response? Or what if you tried it and you had a remarkable response? You should trust your results because in science we often talk about, you'll hear people say, well no, this is what the science says. And science is the best tool that we have been to understand how the body works, how it functions, how you respond to certain tools and strategies. But when we do science, and I, we, I do science every day. I've been a research scientist for two decades.

Dr. Andrew Koutnik [01:07:51]: We study average outcomes in individuals doing a specific intervention, exercise, nutritional, etc. But what we often report is the average. But we know that each person is unique individual. Look no further than just look at my physical appearance and Ben's physical appearance. We're two different looking humans.

Ben Greenfield [01:08:13]: You heard it here first. You're, you're a special snowflake as everyone.

Dr. Andrew Koutnik [01:08:17]: Is and it's true you are. And so if you find that you don't respond well, what if you were the single person who had a negative response? What if you're the single person had a positive response but the average says that it would have been a different response? It doesn't mean you say oh no, that wasn't a real response because this published study said this. The published study tells us what would happen on the average to most people. But each person has to be their own experiment, test things out on their own and see how they respond because ultimately all of us are unique and maybe they don't respond the same way as someone else. And you must trust your own experience but of course do it in a well informed way, understanding how to go about it the right way because oftentimes that's not always the case.

Ben Greenfield [01:09:03]: Yeah. Well folks, if you're listening, I had wanted to have a discussion with Andrew also about you know, nutrition in extreme environments and exogenous ketones and a little bit more about CGMs and blood glucose tracking and plenty more. So we are going to do a part two for sure. I just committed you Andrew. But in the meantime for the show notes for this episode go to BenGreenfieldLife.com Dr. Andrew as in Dr. Andrew. Dr.

Ben Greenfield [01:09:31]: Andrew. I will link to his website, his, his papers, his work and you can leave your comments, your questions and your feedback there. Also Andrew, this has been just this went by so fast. It's just a fascinating discussion. I love this stuff.

Dr. Andrew Koutnik [01:09:47]: Hey Ben, it's been an absolute pleasure especially getting to know and see how you progressed over the years into such an impactful person in the health and wellness space. And to leave one teaser for people out there on part two and for Ben himself, A lot of the stuff we've done in NASA, astronauts in elite level special operations forces communities looking at these nutrients, let's say like exogenous ketone bodies in extreme environments actually give us incredible tools and insights into a lot of similar implications that we see in chronic disease. And a lot of the ongoing studies that we we have and are looking into. In fact we have a number of ongoing trials currently. One of the trials we did actually was with a group called Atrium or Ketone iq, but we've done a bunch of other trials in this space and looking at the cognitive implications, looking at the the imp on physical performance, on long term adaptations that occur with chronic administration for short term administration. But even beyond that, a lot of the work we've done in other spaces I think lend incredible unique insights into how we can take extremes. Whether it be someone living in outer space or performing in one of the most dangerous environments in the world, or someone living with a chronic irreversible metabolic disease. What those things actually teach us that are often overlapping on overall health.

Dr. Andrew Koutnik [01:11:06]: And that's I think something that will be of great interest to individuals to check out maybe in part two.

Ben Greenfield [01:11:11]: Or someone in outer space living with a chronic irreversible metabolic disease. You never know. Yeah, that's all that much, much more. The next episode all right. BenGreenfieldLife.com DrAndrew DoctorAndrew thanks everybody for listening. Until next time, I'm Ben Greenfield along with Dr. Andrew Kudnik, scientists signing out from the Boundless Life podcast. Have an incredible week to discover even.

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