The Insulin & Glucose Doctor: This Will Strip Your Fat Faster Than Anything!

0:00 When we're looking at smoking versus vaping, vaping is probably worse in terms of the damage to the airway and the insulin resistance that comes from it. But this gets worse because we know that insulin resistance is the core for most chronic diseases that are killing us. And there's a handful of other lifestyle habits that's contributing to it. That's horrifying. So tell me everything. Dr. Benjamin Bikman is a leading metabolic scientist. His research focuses on the hidden epidemic of insulin resistance and its devastating consequences. And by regaining control of your insulin levels, he says you can regain control of your life. Insulin is a hormone that affects literally every single cell of the body. But if those cells become insulin resistant, you start to spread the disease. For example, they call Alzheimer's insulin resistance of the brain. And even the most common forms of infertility, erectile dysfunction, and PCOS, insulin resistance is a heavy contributor. Now, 88% of adults in the

0:45 US have some degree of insulin resistance. And people hear this and think America is just fat and metabolically sick. But we're not actually the worst country when it comes to this. And part of it is because of how different ethnicities store fat. And I'll come back to that. But there's two roads to insulin resistance. So there's the fast lane, and I could make you insulin resistant in 6 hours with either of these common three things. But if I removed them, your resistance would go away just as quickly. Now, the slow lane, that's a problem. And there's certain lifestyle habits and problems with our diet that are massively contributing to slow insulin resistance. Now, thankfully, this can be resolved through four pillars, which are very simple. We'll get into that. But why don't we just cycle this off and just take his Ozempic? Well, because people may not know about the negative side effects. For example, 40% of the weight that people are losing on these drugs is coming from Highly

1:32 I have been forced into a bet with my team. We're about to hit 10 million subscribers on YouTube, which is our biggest milestone ever, thanks to all of you. And we want to have a massive party for the people that have worked on this show for years behind the scenes. So, they said to me, "Steve, for every new subscriber we get in the next 30 days, can $1 be given to our celebration fund for the entire team?" And I've agreed to the bet. So, if you want to say thank you to the team behind the scenes at Diabetes Canada, all you've got to do is hit the subscribe button. So, actually, this is the first time I'm going to tell you not to subscribe because it might end up costing me AN AWFUL

2:19 BENJAMIN, WHAT IS THE MISSION THAT YOU'RE ON? My mission is to help people appreciate that much of chronic disease we look at them as these siloed individual distinct disorders with totally distinct origins, and yet much of them uh share a common core. It's as if they're branches growing from the same tree. And the conventional clinical care will look at these branches and give someone a prescription for a medication, which is only going to prune the branch back a little bit, never actually solving the problem. It can just grow right back. And so, we can look at most of these chronic diseases that are killing us globally and and then say, "Okay, there are in

3:06 fact some simple lifestyle changes that can be implemented that will help reduce the risk of not only one or two, but all of the top killers from things like Alzheimer's disease to uh heart disease to type 2 diabetes to uh liver failure or fatty liver disease. All of them share a common metabolic core. That's my mission. And what is that common metabolic core? Yeah, it's a little-known problem called insulin resistance. In fact, when I first started this topic, I stumbled on one paper that documented how when fat tissue is growing, it increases the risk of type 2 diabetes. That wasn't a concept in the early 2000s that was is getting a lot of attention.

3:51 Diabesity, this kind of dual epidemic of wherever we see obesity, we see more type 2 diabetes. And this manuscript outlined something that was to me a revelation at the time. It was so fascinating where when fat tissue is growing, it starts releasing pro-inflammatory proteins. That inflammation caused a problem called insulin resistance. And then that got me into this realm of understanding that other tissues of the body as they become insulin resistant, then you start to spread the chronic disease. And and essentially coming to the conclusion that something like hypertension, high blood pressure, which is the most common cardiovascular problem and the main contributor to heart disease. Well, insulin resistance is the main

4:38 cause of hypertension. Um they call Alzheimer's disease type 3 diabetes or more accurately um insulin resistance of the brain. Even the most common forms of infertility in men, it's erectile dysfunction. Well, that's because of insulin resistance of the blood vessels. In women, the most common form of infertility is polycystic ovary syndrome or PCOS. That's because of the insulin resistance affecting her ovaries and the ability to produce the proper sex hormones. I guess the really important question here is what is insulin resistance? And can you explain this to me like I'm a 10-year-old because for sure. Insulin resistance is it's kind of a it's a disorder that has two parts. It's like a coin with two sides that as much as we think of we we think of one side just because we hear the

5:24 word insulin resistance, but there's another part to it that I need to that is very important. So, insulin first of all is a hormone that we make from the pancreas, a long kind of gland tucked underneath the stomach. And the pancreas is a very busy organ. It makes a lot of different hormones. It makes hormones that come into the blood. It also makes enzymes that go into the the into the intestines to help digest food. But among the hormones that are being released into the blood is insulin. Now, in the person with type 1 diabetes, their immune system has destroyed their beta cells. So, they don't make insulin anymore. That's why for a person with type 1 diabetes, insulin is a life-saving therapy. You're giving them what they're not making anymore. But for everybody else,

6:10 we have beta cells and they're releasing insulin when they need to. Now, usually the main stimulus the main reason the beta cell is releasing the insulin is because blood glucose levels go up. So, I eat sugar. You eat sugar or not even something as obvious as sugar, but bread or or crackers. White rice. Chips. Oh, yes. Yes. So, basically anything that falls into the family of a carbohydrate. So, if the earth grows it, that's a carbohydrate. Um if it's a plant, it's a carbohydrate. Maybe that's a better way of describing it. And so, it's going to have starches and sugars, which all this kind of falls into this family of carbohydrate. Depending on how much starch or sugars that it has, then that will result in a bigger or a smaller blood glucose or blood sugar

6:56 response. But then, if blood sugar is too high for too long, that becomes very harmful to the body. So, insulin comes in um and helps lower the blood glucose. And then, having done its job, insulin comes back down. So, insulin comes out like a taxi and transports all the glucose in my blood to various places around the body to store them. Perfect. Perfect. Yeah, Yeah, that's right. It's that's you can say look at it's a shuttle. It's a taxi saying, "Hey, glucose, come on in. I'm dropping you off at the muscle." So, mostly, just as an interesting tangent of insulin before I finish answering insulin resistance, insulin will open the doors for blood sugar to come in and drive the taxi in, mostly at the muscle and the fat. Muscle and fat tissue need insulin to

7:43 come and bring the sugar in via taxi. However, other tissues and and the brain a little bit as well. Other tissues will still respond to insulin, but they don't need insulin to tell it what to do with the sugar. It just takes it in. But even on those like the liver for example, if the liver sees sugar driving by in a taxi, it just opens the doors and lets it in. It doesn't need insulin to come and tell it to let the sugar in. However, even at the liver and other every other cell has a similar degree of this. The liver doesn't know what to do with it. So, this is back to something I'd mentioned earlier where insulin's thematic effect of the entire body is to tell the body what to do with energy in all of its forms as as these kind of

8:30 caloric rich molecules. What to do with lactate, what to do with ketones, what to do with fats or glucose, what to do with pro- amino acids. So, insulin will tell the body what to do with all of those things. But again, it's most famous effect is to control blood sugar. And that's not wrong because it's most powerful activator is blood sugar. So, with all of that in mind, insulin resistance is two problems wrapped into one. The one problem is the most obvious one, which is that insulin isn't working as well as it used to. So, back to the analogy of the taxis dropping off sugar, if the muscle tissue has become insulin resistant, insulin is coming and trying to pull the sugar-loaded taxi into the muscle, but the muscle's not listening.

9:16 So, say that again. So, the Yeah. Insulin's coming past with the glucose inside it. Well, not not technically. Yeah, but just to sort of go with your metaphor. But maybe to use another one, insulin comes and knocks on the doors. It's like the bouncer Yeah. at the door. It's coming and knocking on the door of the muscle saying, "Hey muscle, I've got some sugar that wants to come in. Mhm. And normally the muscle will say, oh yeah, sure, okay, open up the doors and let the sugar come in. When the muscle is insulin resistant, the bouncer is knocking. Maybe there's even I'm almost getting ahead of myself, but one bouncer maybe two or three bouncers pounding on the doors of the muscle cell, but the muscle cell's not listening. It's become deaf. That's the insulin resistance of what we call insulin resistance, where some of

10:01 insulin's effects, like helping lower blood sugar, it's not working very well anymore. And the muscle is just an obvious example because there's so much of it. You know, it is the biggest tissue on the average individual. Someone who's very obese perhaps now has more fat tissue, but even people who are overweight, most of us is muscle. So, that's a good it's a good tissue to look at. So, part of insulin resistance is that of all the things insulin's trying to do, including lower blood sugar, it doesn't do it quite as well as it used to. Some of the cells or tissues of the body have become deaf to insulin's demands. Now, however, at the same time that's happening, insulin levels are higher. And that is really important. Um and I'll I'll

10:47 mention an example in just a moment that highlights the difference between the two, but we have to consider anytime we talk about insulin resistance, we think of two things happening um in concert. One, insulin isn't working quite as well as it used to in various places of the body. At the same time, insulin levels are higher. And that kind of takes us back to the um the muscle cell, where I'd mentioned getting a little ahead of myself, that a bouncer is knocking on the door, and once upon a time the muscle cell would hear that one polite knock from that one bouncer or one molecule of insulin, if you will, and it would open the door and let the glucose or the blood sugar come in. But now the muscle cell um the the the bouncer insulin's knocking on the door, but the muscle

11:33 doesn't listen. It's resistant. And so, the body has adapted, and it learns, "Okay, well, if one bouncer wasn't enough, let's send an angry mob of bouncers." And then the glucose the muscle will start to open the door. And and and indeed it can. So, those two problems go together. On one hand, insulin isn't working as well as it used to. That's what gives it the name insulin resistance. But there's another part that is equally present, which is that blood insulin levels are higher. Now, there's um earlier at the outset of the conversation, I mentioned that even infertility has an origin has has some degree of um development because of insulin resistance. And it's a perfect example of both of these parts of insulin resistance, where

12:20 in some instances insulin isn't working very well, always with insulin resistance blood insulin levels are higher. So, for example, erectile dysfunction is the most common form of male infertility. In fact, its connection to insulin resistance is so strong that just a few years ago I I was so struck by a title of a paper that had just been published, which stated something like, "Is erectile dysfunction the earliest manifestation of insulin resistance in otherwise young healthy men?" Now, what is the connection? It's because in a normal erectile function, in order for the man to have normal erectile function, he has to experience a pretty dramatic increase in the size of the blood vessels in his body. The

13:05 blood vessels expand, that increases blood flow, and then he has normal function. Part of that signal that tells the blood vessels that it's time to expand is actually insulin. And so, this is what I said earlier, where insulin does so many things in the body, and we only think of it as being relevant to glucose, and that's not fair. Insulin does a a of stuff. Again, including telling blood vessels to expand. Now, unfortunately, in the case of this this unfortunate man, his blood vessels become insulin resistant. So, now it's insulin coming and knocking on the doors of the blood vessels saying, "Hey, it's time to expand and increase blood flow." But, the blood vessels don't respond. They don't listen. So, they stay constricted, blood flow stays insufficient, and thus he has erectile

13:52 dysfunction. Now, I don't want to be insulin resistant. No. No one does. No one does. So, so tell me how it happens. Yeah, right. Yeah, so the origins are so important because it helps us understand why we've gotten into the situation we are, where it's the most common problem worldwide. There are two pathways to insulin resistance. So, two two roads to get to the same destination. Again, the destination being insulin resistance. There's the fast lane, which I call fast insulin resistance, and it actually has three lanes, which I'll describe in a moment. Then, there's the slow insulin resistance, which is a more it takes a little longer to get there, but at the same time it takes a little longer to get away from it. So, I'll start with fast insulin resistance because the slow one ends up getting a little excitingly

14:38 complicated, but in a cool way. So, with fast insulin resistance, there are three things that I could take you to a clinical lab, and I could make you insulin resistant in 6 hours with either of these three things. But, as quickly as it settles in, if I remove those things, your insulin resistance would go away. So, these are fast causes, and they're fast resolution. They are stress is a is a primary cause of fast insulin resistance. So, too is inflammation. And then lastly, and this is going to sound somewhat paradoxical, too much insulin is also a cause, and I'll end with that one because I think it's the most important. Then transition to slow insulin resistance. So, anytime the body

15:25 is experiencing too much stress, it will very quickly become insulin resistant. Now, as a professor who teaches endocrinology, no surprise, I define stress in the context of hormones. And there are two primary stress hormones, cortisol and what we call in the US epinephrine or in the UK adrenaline. Those are the two stress hormones. Now, those hormones are very distinct. They have almost nothing in common. But like when you are feeling a little stressed, it's both of those, especially adrenaline {slash} epinephrine, that are making you feel a little jittery. It's making your heart beat a little faster. You're a little more alert. Um that all starts to play into a stress response. But what those two hormones have in

16:10 common is that they both want blood glucose levels to climb. It's kind of their way of saying, "Hey, we don't really know what's going on right now, but we want to be ready to run away." Or that's the fight or flight kind of aspect to stress. And so they want to push blood glucose levels up, and they do very well. That, of course, puts them at odds with the hormone insulin. Cuz these two, epinephrine or adrenaline and cortisol, the two stress hormones, they're pushing glucose up, insulin wants to push it down. So, the more of the body is has those stress hormones elevated because of, say, sleep deprivation, that's a very effective way to increase cortisol, or they are taking too much drinking too much caffeine, that is a way to increase epinephrine

16:55 quite strongly. If both of those signals are too incessant, or the you know, they they continue to be present and climb, then insulin has to work harder and harder. And then we have insulin resistance. So, stress is a cause of insulin resistance. But then next is inflammation. You you know, you you and I were commenting about earlier about how, "Boy, there's a cold going around. People it's flu season. Even then, if a person were wearing a continuous glucose monitor on the back of their arm, measuring their glucose levels, they would see their glucose levels are much much higher like significantly higher during the time that they're struggling with this infection. That is a reflection of insulin resistance. Insulin's having a harder time keeping

17:40 the blood glucose levels in check. Anytime inflammation is up, insulin resistance will be up as well. Even in things like autoimmune diseases, there are reports in humans that document the degree to which someone has say active rheumatoid arthritis. Their their joints are achy and because of of an autoimmune attacking of the joints, they will note on some days, like every autoimmune disease, there is an ebb and a flow. Some days it's good, some days it's bad. And on the bad days, if you measure their insulin resistance, it is absolutely locked with the degree to which their immune system is turned on or off or higher or lower. So, inflammation is another cause. And then the last one of the fast lane of insulin

18:26 resistance is too much insulin itself. Now, the astute listener will realize the kind of circular thing I've just presented by invoking high insulin as a cause of insulin resistance because they will also think, "But wait a minute, Ben. You just said that high insulin is also a consequence of insulin resistance." That, you know, back to the bouncer knocking on the the the door of the muscle cell, if one bouncer wasn't enough or one molecule of insulin wasn't enough, the body will say, "Okay, well, let's send 10 molecules of insulin." So, high insulin is both a consequence of insulin resistance, but it's also a cause. And this is reflective of a fundamental principle in all of biology that if there is too much of a stimulus,

19:14 a cell, if it's capable, will try to become resistant to that stimulus. This would be like a funny analogy of in in in my in the Bickman home, my darling wife is home with the children. That is what she wants to do. She She is full-time mom. When I'm home, and I try to be home as much as I can, it's funny for me to note the difference in how quickly we each respond to our children. I will hear my child saying, "Mom. Mom. Mom." And she's not responding. Mom has heard this for so much that she's become kind of selectively deaf to when my children are demanding her attention. I'm not as around my children quite as much cuz I'm working during the day. And so when I hear that, it's a very fresh signal to

20:00 me. I've not heard it so much that I've become deaf to it. And so I will respond even though I'm in the other room because I'm so much more sensitive to the clamoring for attention. This is like the body in response to insulin. If there is always insulin, it's always going up, always going up, the body will start to say the muscle cell will start to say, "Boy, insulin, you are knocking on my door all the time. This is getting old. I'm not responding anymore. I'm not going to listen as much as I was before." So in that sense, insulin, too much insulin becomes a cause of insulin resistance. And back to what I said earlier, I could take you into the lab, start infusing you with just a little drip of insulin to increase your insulin, and over just a few hours, you would become demonstrably

20:46 less sensitive to it than you were before we started. But again, as I would take that away, give your body a few hours, and it's back to normal. In every one of those instances, it's a fast onset, and it's also a fast solution if we can take it away. If we can take it away, but if we can't take it away, does it become sort of chronic? Yes, so that especially all of these can contribute to a more lingering insulin resistance, but especially insulin. Where I focus on that one the most because of not only its relevance to the slow lane, but also just how present it is where 70% of all calories globally are carbohydrates. And now, perhaps with the best of intentions, our experts are telling us that we should be eating six times a day.

21:32 And so, we eat we wake up in the morning, insulin has finally been coming down while we've been fasting overnight. Insulin gets to take a little bit of a break. We're fasting. Then we break that fast by eating breakfast. And in the UK as it is in the US, by and large, this is going to be a very starchy sugary breakfast. It's toast with some jam or a cereal or it's bagels. That is going to be that is almost pure glucose. And so, what do we do? We wake up, we eat breakfast, we spike our blood sugar levels, and insulin has to come up. Insulin will take longer to come down than the blood sugar will. It will wait in the blood to make sure that all the blood sugar has gone back to normal. So, depending on how much carbohydrate we ate for breakfast, it could take our insulin levels three or

22:19 even four hours to come back down to normal. Long before it's had a chance to come back down to normal, we've had a mid-morning snack, of course. We need to go get a sugary coffee and another bagel or something. And so, after just a couple hours, we do it again. And once again, before insulin has had a chance to come back down, we have a starchy carbohydrate-heavy lunch, then an afternoon snack, and then a carbohydrate-heavy dinner, and then of course we have to have an evening snack before we go to bed. So, the average individual is spending every waking moment in a state of elevated insulin. And thus, the signal never really goes away because they they never give themselves a break. But one of the consequences of that I mentioned, which is that it directly causes insulin resistance.

23:04 But, when insulin is high, it starts to have a signal on the fat cell. And that then brings us to the slow insulin resistance, where you have something happening in the fat tissue that begins to set the stage for insulin resistance in the entire body. And it takes longer to settle in, but it takes also longer to go away. That's why I call this one slow insulin resistance. Now, in the case of insulin, most people So, the the the the key with the Yeah, I'll explain it this way first. So, the most relevant feature with fat tissue contributing to insulin resistance is the size of each fat cell. When we typically think of fat, we would maybe say, "Okay, Steve has um I'll do this in kilos for the UK audience. Steve has 10 kilos of fat on your entire body.

23:51 That's probably too much for you. Ben has 20 kilos. And yet, it's possible that I'm healthier metabolically than you. Um and that's because it's not the mass of fat that matters most. It's the size of the fat cell that matters. This is why women, despite universally being fatter than her male counterparts, are healthier with regards to insulin resistance and every single metabolic problem. It's because women, as a result of her particular sex hormones, have more fat cells, but they're smaller. So, she has more fat, but smaller fat cells. And small fat cells are healthy, insulin sensitive anti-inflammatory fat cells. The but the bigger the fat cell gets,

24:37 the more it initiates a cascade of events or a series of events that creates insulin resistance. Am I right in thinking we have the same amount of fat cells for our whole life, pretty much? That's really, really safe assumption for most people. Yeah, for most people the a fat cell um sometimes students will hear that fat cells are immortal. That is not true. But, they're long-lived. Fat cells will live about 10 years. And so, typically, by the time you if you think of if you look at a newborn, during infancy, childhood, and puberty, the number of fat cells is going up up up up up. Once they finish puberty, so mid to late teens for a young woman, late teens or even early 20s for a young man, usually at that point the number of fat cells they have is going to be very static.

25:22 This is something people don't really understand, and I actually need to discover it from doing this podcast and speaking to so many experts about this, that we pretty much, especially as an adult, have the same amount of fat cells, really regardless of what we eat. Yes. And it's actually just the fat cells we have shrinking Or growing. or expanding. Exactly. That's exactly right. Now, there are differences across makes liposuction a pretty bad idea. it in fact, it makes things worse. Please, let's make sure we come back to that. Okay, I'll write that on my list. Because it really becomes the person ends up their vanity ends up really ruining their their their future metabolic outcomes. But, there are differences across ethnicity. Like um this is a little oversimplified, but not much. On one end, you'd have Caucasians, kind of

26:08 northern European Caucasians. On the other wind end, you'd have East Asians, like uh Chinese, Japanese, uh Korean East Asians. And And then, if you look at that same spectrum of people making fat cells through their life, an East Asian will be making fat cells and then stop right about here. About sort of So, very few fat cells, relatively speaking, across all the ethnicities. They have very few fat cells. A Caucasian on the other end of the spectrum, they went way higher. And so, this guy, let's say American Ben versus Chinese Ben, overly simplified, but but here we are. Um so much of fat mass isn't the number of fat cells, even though American Ben has more, it's the size of the fat cell. So,

26:53 I could be the same percent body fat really as Chinese Ben, um but that would just be because my fat cells were just that much smaller. But this is the problem then. If you have let's say American Ben and Chinese Ben both gained 10 kilos of pure fat over the next 10 years. Very easily done. Most people do that quite often. Caucasian Ben just doesn't look as good in his speedo. Um which is a pasty Caucasian, he's not going to look particularly good in that speedo anyway. But I'm just indulging a little more than I was before, but otherwise I'm healthy. My blood pressure is fine, my blood sugar is fine, everything is normal. Put that same 10 kilos of fat on Chinese Ben, hypertension, type 2 diabetes, fatty

27:38 liver disease, infertility. Um and that is because Chinese Ben had fewer fat cells to start with. And so those fat cells, as the body was told to store fat, those fat cells were getting much, much bigger, much sooner. And the fat fat cell promotes insulin resistance very, very readily. And so that logically moves into this the question of what makes fat cells grow? And it is two essential variables that we only ever look at calories. And yet, if you take a person with type 1 diabetes and say, "I want you to eat 10,000 calories, but don't give yourself your insulin injection." They cannot gain weight. It is It is literally impossible

28:25 for the type 1 diabetic to get fat if they are skipping their insulin injections. In fact, this is so known that if you take Let's imagine a young woman who would maybe have more pressure to be thin than her male counterpart, although it's happening more in males, too. Imagine a young girl who gets diagnosed with type 1 diabetes at the age of 13 or 14. Very impressionable time. She's very worried about how how she looks and how thin she is. She learns that wait a minute, I can eat whatever I want and all I have to do is not inject my insulin and I'll be as skinny as I want and it works. It works so well that it's actually a formal eating disorder called diabulimia. So this the fact that this exists is absolute proof

29:10 that the growing and the shrinking of the fat cell is more complicated than just calories being high or low. Because like I had said earlier when I talked about hormones, hormones are a way for the bot for the very tissues of the body to know what it ought to do with energy. And so a fat cell will have energy all around it and if it doesn't have insulin to tell it what to do, it won't do anything with it. And or maybe to make this more direct back home in my lab my students my students are growing fat cells in Petri dishes. These fat cells are swimming in a little sea of calories, lots of glucose, lots of fats and yet they stay really small until we add insulin. The moment we add insulin into that little Petri dish, if we check those cells 4 hours later,

29:56 they're immediately fatter. If we check them 4 hours later, they're fatter still. Now they know what to do with the energy they have. So with slow insulin resistance it develops when fat cells get really really big. It's like a because they have to tell insulin, insulin you continue you you are telling me to keep growing, I can't keep growing. I'm so big that I'm going to pop. I mean literally the fat cell can get so big that it degrades its membrane. It's like a water balloon that a naughty little boy has overfilled and it's about to burst. The fat cell doesn't want to burst and so it tells insulin, insulin you are trying to make me grow. You're telling me to grow. I can't listen anymore. I'm becoming insulin resistant to stop growing. So insulin makes you fat?

30:41 Oh very much. Now, if you So, so I A moment ago I said that the big fat cell has two variables. You must have both. You must have both a signal to tell the fat cell to get big, which is insulin. It is the There's no other signal that can do it. You can in a human just simply take away the insulin, like type 1 diabetes. It doesn't matter any other hormone in the body, it does not matter. They cannot get fat. They could Again, they can eat thousand They could eat 10,000 calories of chocolate cake. They cannot get fat. Not only can they not get fat, they can't hold on to their fat. Cuz if there's no insulin to tell the fat cell to hold on to it or get big, it has to shrink. It's breaking down its fat. So, the body goes into such a dramatic fat burning state in the absence of insulin that keeping fat

31:28 becomes impossible. So, the insulin signal's necessary to tell the fat cell what to do. But, the fat cell will say, "Okay, insulin, you're high. You're telling me to grow, but what am I going to grow with?" That's where the calories come in. Now, the fat cell will say, "Hey, fats and glucose in the blood, insulin has told me to get big, and so I need to pull you in to help me grow. You're going to give me the bulk." And if you have one without the other, it is death. So, if I'm eating 2,000 calories and I have a different insulin sensitivity to you. Say we both eat 2,000 calories and I'm insulin resistant, doesn't that mean that I will You'll store more as fat. Oh okay. Yeah. Yeah, so so your body now it would

32:14 partly depend on There are people where you you if your if all of your fat cells had reached its maximum point, then you're done. You're not going to gain more fat. You're just going to become more and more and more insulin resistant. Okay fine. So, you kind of start limiting yourself. But, there are studies in humans to show that if you give humans isocaloric diet meals, so the exact same number of calories, but they in the same amount of protein, but you differ those meals based on the amount of carbs to the amount of fat. So, let's say two meals, exact same calories, 2,000 calories, or that's in one meal, that's too high. 1,000 calories in one meal. One version of this is the conventional way of eating, which is lower fat, higher carb. The other meal, same number of calories,

33:01 but it's lower carb, higher fat. This lower carb, higher fat version will have a lower insulin response, and they they will store less fat from that meal. And their meta- And someone would say, "Well, where do the calories go?" You can't this it's the laws of thermodynamics. You can't destroy energy. The metabolic rate will go up. So, when insulin is low, if you have someone going a full day eating the same number of calories, but lower carb calories, their metabolic rate will be almost 300 calories higher in that day. And metabolic rate is the the total amount of energy that it just costs you and I to just live. Okay. So, It was going through the day. But that's But that's a significant amount. Like, if you and I were to go exercise and say, "Let's go burn 300 calories." We

33:47 got to be on the stair stepper for an hour or something. So, it's 300 calories, but at the same time, if your insulin is low, you're burning so much fat that you start making ketones. And I I don't intend to get onto that topic quite yet, but suffice it to say, every molecule of a ketone has a has a caloric load roughly similar to glucose. And one of the And And what the body when it starts making a lot of ketones, it starts eliminating the ketones. So, every time someone is breathing out ketones, they're literally breathing out calories. Or they're urinating, and they're urinating out ketones if they have higher ketones in their blood. They're urinating out calories, because ketones have energy. And so, this is the way that if insulin is low, it becomes impossible for the

34:33 body to hold on to its energy. It is so determined to spend energy that it will both increase metabolic rate, and it will make the energy, the calories be wasted in the breath and in the urine, and and in the form of ketones because ketones have calories. Ketones are energy. Now we're just dumping them out into the universe. It's worth, before we talk about how to keep my insulin levels low so that I can benefit from all the health benefits we've talked about, it's probably also worth just spending a little bit of time trying to understand the evolutionary basis of insulin resistance. There are some theories that are very interesting that attempt to explain why is it that we became so fantastically different from let's say our closest animal relatives, other primates like chimpanzees or or apes.

35:20 What was the difference that had us become so different than them? One of the leading theories is a is a theory called the expensive tissue hypothesis. And it actually does have something to do with ketones. In the expensive tissue hypothesis, as the theory goes, our earlier ancestors deviated in this kind of animal family line because we started eating more meat. We started eating food that was so nutritious, so nutrient dense, so loaded with good calories and all of the fats and proteins that we need, that it allowed two very distinct changes to occur in us compared to other primates. One, our intestines became significantly shorter.

36:06 So if you compare the human digestive tract to any other primate animal, if if we are a primate, um then if you look at the intestines, they're fantastically different, particularly the large intestine or the colon. Because our ancestors, as the theory goes, began eating meat, we didn't need the the as much. Um and the colon is a place for food to ferment. And so, if you're eating a lot of plant matter, like other primates do, you need a much, much larger colon. So, we started eating food that was so nutrient-dense, our colon shrunk considerably. We didn't need to waste energy on a big, busy colon. At the same time, as we were eating food that was so nutrient-dense and so loaded with good fat,

36:52 it allowed us to have more time to be curious and explore. And so, at the same time our intestines were shrinking, because we didn't need them to be so big, our brain was growing. And and it's because it had so much nutrition, including ketones. So, ketones are an extraordinary fuel for the brain. In fact, one of the reasons why a baby that is born premature will be more likely to have learning disorders later in life, is because premature baby didn't have time to get very fat. And fat baby is healthy baby. And fat baby gets into ketosis. Let's say you and I were to to fast straight for 2 days. If you took a 6-month-old baby, that baby would be in a deeper state of

37:37 ketosis in 2 hours than you and I would be in 2 days. Because the baby is burning so much of its beautiful chubby fat, and the more the body burns fat, the more it makes ketones. And the tissue of the body that appears to benefit the most in response to ketones is the brain. The brain, the moment ketones hit the blood stream, the brain immediately starts taking in ketones for a fuel. Very often, I have students who have had a professor, perhaps with the best of intentions, but ignorant nonetheless, tell the student that the brain the main fuel for the brain is glucose, that the brain prefers glucose. And I show them just one or two papers to prove that wrong immediately. And it is reflected in in in this idea

38:22 which if if to use some convenient UK units, if blood glucose is 5 millimolar, that's a concentration, a way of measuring an amount of of something. Blood glucose may be 5 millimolar or 80 mg per deciliter for the American audience. Um that would be a normal glucose. And if you and I were to fast for 24 or so hours, we may get up to about 1 millimolar of of ketones. And yet even then, the brain has already switched to get the majority of its energy from the ketone. And so don't tell me that in this dynamic the brain prefers this one because this one's five times higher than this one. And even in that scenario, the brain is already getting more than half of its energy from the ketone. So all of this is my long-winded

39:08 way of saying, when we look at the principles of evolution, one of the leading theories is this idea that we began eating essentially a meat-heavy diet that again is so nutritious that it allowed our brains to grow. Maybe one final point on this, although it is a bit of a barbed comment, people may find this somewhat amusing or disappointing or frustrating, the title of a book just published which is that vegetarians have smaller brains. This is seen in humans that the less a human eats meat, then the smaller the brain becomes. The brain is so dependent on the nutrient density that comes from animal-sourced foods that it will suffer um when it doesn't get them. Interesting. I mean, that's a controversial thing to say. It is, and you can cut it out.

39:54 But it really is it's a real thing. And why does depression go up so much when people stop eating animal-sourced foods? It's because you are depriving the brain of what it needs. What is it exactly you're depriving the brain of in that situation? Yeah. Yeah. So at least among other things, at least it would be the the essential omega-3 fats. So there are three omega-3s, and you humans can only we can only get one from plants, but it's one that the humans don't use. We need the other two, and they only come from animal source foods. And you could supplement. Absolutely. Right. I mean, that's what I was Yeah, you can, but but that that So, the the solution in that regard is the vegan must be educated enough to know what they're deficient in, and then wealthy enough to afford the supplements to make up for it. So, is that the the only evolutionary sort of hypothesis towards why we

40:41 develop this insulin resistance? Mm. Oh, yeah. In fact, it's funny that you bring the question up again because I realized I didn't quite answer it that way. So, insulin resistance, why would it exist at all? It would probably be a way for the body to know when it was needed to hold on to energy a little better. So, now Now, I say that now, and and someone would think, well, but you just why would I want to hold on to energy in a way where it's causing hypertension and Alzheimer's disease and increasing the risk of heart disease? Not all versions of insulin resistance are negative. So, there is um there is what all the insulin resistance that you and I have been talking about is pathological insulin resistance, or harmful insulin resistance. Insulin resistance that serves no good purpose,

41:27 and it's making us sick. However, there is insulin resistance in human development, which is physiological, or helpful. It's supposed to happen. And that is the two P's of physiological insulin resistance, puberty and pregnancy. Because in both of those instances, as we outlined earlier, when the body's insulin resistant, insulin is high. That's not always bad, because insulin wants things to grow. It is like a fertilizer in the body. Now, sometimes it's misplaced, and results in problems, like increasing the risk of cancer, for example. But in other instances, if you have a young child who needs some explosive growth during puberty, well, then that's really helpful. Insulin's telling the body to store more energy, to build up tissues, including

42:14 muscle and bone, but also including fat. So, in pregnancy, insulin's playing a role in growing the placenta. is. The breasts. Yes, so in the woman, after she's finished puberty, the only other time of growth she'll ever have will be pregnancy. And and so, those are the two instances where the body has become insulin resistant to take advantage of the heightened scenario where it can grow. Because the woman's body needs to more fat. goodness, yes. Yes, so her body not only needs to grow tissue mass, like the uterus has to get much bigger. She has to grow a placenta. She also needs to become a little insulin resistant to give a little more glucose to her baby, because she is after all now living for two people. And so, as she as her body becomes insulin resistant, it actually facilitates the growth of the baby a little more rapidly. But as you noted,

43:01 it helps her store more fat, and progesterone is another hormone that even accelerates that process. But basically, it's the her way of her body's way of saying, "Hey, I am committing to growing another human, and it's going to be metabolically very demanding, and so I'm going to have as much extra fat or much as much extra energy as I can in order to ensure that if there's any sort of scarcity in food that happens during the course of the pregnancy, I'll have enough energy to get through it all. And then maybe I'll even have enough to continue to feed the baby with lactation after the baby's born." What is gestational diabetes? Yeah, it's a great question. Gestational diabetes is essentially type 2 diabetes

43:46 of pregnancy. So, it's perfectly timed question because if you look at the average woman um who is very healthy, very insulin sensitive at the beginning of her pregnancy. So, glucose is normal and insulin is normal. Over the course of her pregnancy, she stays normal healthy pregnant woman, which is to say she has physiological insulin resistance. She doesn't get diagnosed with gestational diabetes though, which means her glucose is normal. But to keep her glucose normal because she is insulin resistant, but for a purpose to help her body grow, her insulin levels are high. And then the glucose is still in a normal range. And then in some women, especially if she has a family history of type 2 diabetes, the insulin resistance goes too far.

44:33 Now, she has high insulin, like all pregnant women do, but she's not able to keep her glucose levels in check. So, if I'm eating loads and loads of sugar throughout pregnancy, That will compound the problem. Absolutely. So, then she will go from the normal insulin resistance of pregnancy into the insulin resistance of diabetes. So, it really is like type 2 diabetes, but a microcosm of it, a mini version that was really instigated or initiated because of the pregnancy combined with a bit of a genetic predisposition combined with her eating the worst possible way. Does that then impact the future baby? Oh, for sure it does. Yeah. So, think about it's almost like the baby is develop literally developing in a hyperglycemic hyperinsulinemic environment. So, the baby's get the baby

45:19 gets hardwired to want to continue to exist in a state of high insulin and high glucose after the baby is born. And so, yes, the offspring of mothers who have gestational diabetes are significantly more likely to gain weight and be chubbier or fatter than their counterparts and to later develop type 2 diabetes. Yeah, a resounding yes. I read in your book that these infants have a 40% higher chance to be obese and have metabolic complications in their teenage years and beyond. Yes, I mean a significant thing and I I say that with all of the sympathy I can for the mother who may be struggling with this, but it is certainly a motivation for mom to just be mindful of what you're eating. One of the things that that I saw the other day on social media, which I wanted to ask you about, was this. I've

46:05 got a picture of it here. Um it was someone online that posted this photo, and they said, well, this graph, and they said, we need to figure out what's going on here. Um this is the graph. I'll put it on screen for anybody that's watching, but also it'll be linked in the comments section below. Um it essentially shows that over the last, let's say, 20 years, there's been a really significant rise in cancer amongst women, but when we look at cancer amongst men, it's pretty flat. Mhm. Um and this is cancer incidence by age and gender up to 49 years old. Mhm. And I was wondering if you had any thoughts on why this is happening. Yeah. Yeah. Yeah, a few thoughts come to mind. Um whenever I see these kinds of reports, I always make sure I look

46:52 firstly at the What are they actually measuring? So, just to set the stage, this is the number of women who are being diagnosed with cancer, so not dying from cancer, but it's going up. So, one one simple explanation, although perhaps the most disappointing, could be that more women are going in for testing younger, and so we're just seeing kind of an artifact of more women are just going in sooner, and they're detecting a problem that they wouldn't have otherwise detected, you know, for 10 or 20 years. And which is a good thing. You want to detect cancer as soon as possible. So, that's the boring answer, that it could be a reflection of just more women going in for ultrasounds or MRIs or mammary scans, whereas men don't ever get tested for anything, which is why we die more from everything, possibly. But to give a more

47:38 exciting answer, this is very, very likely almost entirely driven by breast cancer. Um breast cancer is the main cancer for women um by far. And so, if I had to guess, I bet almost all of this increase in cancer incidence is because of breast cancer. Why might that be going up? I would suggest there's probably a couple instances. One, um although people might not appreciate this, is that one of the best ways for a woman to reduce her risk of breast cancer is actually having babies. It's very well known, um very well documented, that if a woman um has a fam- it has babies and breastfeeds, her risk of um breast cancer goes down. So, yeah, in fact, it's very meaningful. I actually don't know um the reasons for it. It could be the changes in estrogens during lactation phase.

48:25 I've just I've just actually done a quick search here to I put a picture of that graph into AI and asked it the same question, and it said pretty much what you said. It said, "There's a rising breast cancer incidence according to Cancer Research UK." The other one that it came up with is obesity trends. Oh, yeah. I promise I was going to talk about that. I wouldn't leave that. Yeah. Sorry for interrupting there. No, no, no problem. Uh and then the other one was delayed childbearing. That's what I'm saying. Which is what you were saying. Yeah, so as child rates as childbirth rates are going down, it does increase the risk of breast cancer. Now, as I I'm a cell biologist, right? I like to understand the direct mechanism. And so, as much as I invoke the perhaps lower rates of childbirth among women, I don't know the mechanism, so I'm sort of loath to describe it. The mechanisms I'm very familiar with are the metabolic, um which is if you take a breast tissue

49:13 that is tumor tissue and compare it to like if you take a breast tumor and compare it to the normal tissue right next to it, like that it would have shared its origins with, the cancer from the breast will have seven times more insulin receptors than the normal breast tissue. So, the idea of this tracking quite nicely with obesity rates going up over the past 20 years, I wouldn't say that it's the obesity per se, but I would say it's the entire metabolic milieu, which is the insulin resistance, that as much as the high insulin is promoting fat cells getting bigger, that high insulin is also accelerating the growth of the tumor cells. Because again, the main one of the main mutations in breast cancer is a sevenfold so a seven times increase in the number of insulin receptors. And

50:00 insulin wants to tell things to grow. So it's no surprise that almost every tumor that's ever been measured for having insulin receptors will have a lot more. It's basically telling its neighboring cells, "Insulin's going to come by and it's going to tell us all to grow. I want to grow more than you." And that's what cancer is. Cancer is growth, unregulated growth. Insulin tells things to grow. So the connection between obesity with the rising incidence of breast cancer is very, very likely a consequence of the rising incidence of insulin resistance. As you guys know, Whoop is one of my show sponsors. It's also a company that I have invested in and it's one that you guys ask me about a lot. The biggest question I get asked is why I use Whoop over other wearable technology options. And there is a bunch of reasons, but I

50:45 think it really comes down to the most overlooked yet crucial feature. It's non-invasive nature. When everything in life seems to be competing for my attention, I turn to Whoop because it doesn't have a screen. And Will Ahmed, the CEO who came on this podcast, told me the reason that there's no screen. Because screens equal distraction. So when I'm in meetings or I'm at the gym, my Whoop doesn't demand my attention. It's there in the background constantly pulling data and insights from my body that are ready for when I need them. If you've been thinking about joining Whoop, you can head to join.whoop.com/ceo and try Whoop for 30 days risk-free and zero commitment. That's join.whoop.com/ceo. Let me know how you get on. You know, one of the big subjects you

51:30 touched on at the start was the was Alzheimer's and dementia. Yes. And I have heard several people on this podcast tell me that they think of Alzheimer's as type three diabetes. Worldwide, there is a new case of dementia every 3.2 seconds. Um it seems like I don't know if this is true, but is Alzheimer's and dementia on the rise? Oh, yes. Yeah, it is. In fact, it went from not being even on the radar to being a top 10 killer. Um now, it's interesting how people even die from Alzheimer's disease. It's a very kind of vague death. But yeah, Alzheimer's disease is one of the top 10 diseases now. Um certainly in the West. Um and and I would argue it's because it has a metabolic origin. Now, one of the interesting things about Alzheimer's disease is we have spent

52:18 billions of dollars on Alzheimer's research trying to identify the the plaque. So so just to set the stage here so that people listening can appreciate this this paradigm shift that's occurred in Alzheimer's research. Originally, and even in many people still, people thought that Alzheimer's disease is the result of these plaques accumulating in the brain. These kind of little proteinaceous little thick things that are preventing neurons from sending the signals throughout the brain for the brain to think and and and have normal cognition. And and yet, there are those of us and I am proud to say I have long been one of them who has said that the plaque-based theory doesn't make sense. We have had drugs that have been available for human use for years that have effectively

53:05 reduced plaques in the brain and yet did nothing to improve cognition. So that is an immediate challenge of the plaque-based theory of Alzheimer's. Even further, even beyond older than that evidence, when you would look postmortem or look at tissue donor, people who passed away, you would look at the brains of people who died with confirmed Alzheimer's disease at the time of death and look at the brain of someone who died without any evidence of any cognitive decline or any compromised thinking whatsoever. And you would be just as likely to find plaques in both brains. So the So whether the brain had Alzheimer's disease not, you would still see plaques in the brain. So the whole idea that plaques mattered has long been controversial. And just to put a fine point on it before transitioning to the

53:51 metabolic origins, about two or three years ago, they found out that the very first published papers that implicated plaque as a cause of Alzheimer's disease were based on fabricated data. So the scientists who published those first reports that led to the entire theory that Alzheimer's disease is plaque-based were called out as fraudulent. And and indeed, all of it was fabricated. So the entire idea that Alzheimer And and we have spent billions of dollars on studies to try to how determine how do plaques cause cause Alzheimer's disease? Why when we reduce plaques, it doesn't appear to help the disease. Because the plaques had nothing to do with it. That's just something that some brains have. Some brains have more of

54:37 these little specs than other brains, and they don't contribute to Alzheimer's disease at all. Now, what did can what kept rising to the top, and I would hope now is the dominant theory, is that people with Alzheimer's disease almost always have some detectable instance of insulin resistance, if not full-on diabetic type 2 diabetes. Now, I will say personally, I don't like the term type 3 diabetes because it makes it sound like it's a whole new version of diabetes. To say it more succinctly and accurately, it is simply insulin resistance of the brain. And the brain is a very hungry organ. It is in what I teach as as a tri a trinity of high metabolic rate organs.

55:22 That there are three organs in the body whose metabolic rate is so high that it just really sets it apart from everything else. And the brain is one of them. The brain has a very high metabolic rate. So this is a very hungry organ that that a lot of energy all the time. But the brain is unique in that it primarily will only use two fuel sources, and I've mentioned them, namely glucose and ketones. But glucose in that section of the brain that gets compromised with Alzheimer's disease, the glucose can't just come straight in. It needs someone to open the door for it, and that is insulin, of course, just like we described with the muscle cell. Where in order for the glucose to go into the muscle, insulin had to come and knock on the door, if you will. And then the muscle, being a polite, responsive

56:08 host, would open and allow the glucose to come in. The brain is similar. That in that section of the brain, it has doors that need insulin. It's locked until insulin comes and opens them. So, even though glucose levels may be high in the blood, like in type 2 diabetes, you would think, "Well, the brain can just get all the glucose it wants." And yet it cannot because it has insulin regulating the entrance of the glucose. And if the brain is insulin resistant, there's not enough glucose coming in. And thus the brain is forced to rely on the only other fuel that it can rely on, namely ketones. But the same person who's eating all the time to keep their blood glucose high all the time has so much insulin in their blood that they're never making enough ketones to fill the gap. You

56:53 know, mind the gap, and the brain has an energy gap now. And where where the brain needs, you know, an amount of energy, I'm kind of acting it out for those that are watching, but the brain has a certain energy demand that it needs. And if there's a lot of glucose in a healthy insulin-sensitive person, glucose will fill all of that need. But as the brain becomes progressively insulin-resistant, it cannot get all of its energy from glucose. And thus there's an energetic gap. And in the absence of ketones, there's nothing to fill that gap, and the brain says, "Well, I don't have enough energy to keep functioning as well as I did before, so I have to reduce my function, which manifests as a reduction in the ability to think and process. In other words, cognition goes down. But, what's so interesting

57:39 is I just got finished describing a scenario that scientists refer to as brain glucose hypometabolism, or a reduction in the amount of glucose the brain is using. There are scientists that measured this. We don't in my lab because we don't do these kinds of techniques, but you can actually infuse people with a glucose that you can take pictures of and see how much the brain is taking it in and metabolizing it. In Alzheimer's disease, the brain is not getting as much glucose, so they call that a hypo, or a reduction in metabolism of glucose. And as much as you and I are describing that scenario as relevant for Alzheimer's disease, you can essentially open up the book of neurological disorders and see the same thing. Depression has a brain glucose hypometabolism to

58:25 it. Migraines have a brain glucose hypometabolism. Epilepsy um and Parkinson's so all of these disorders of the brain, of the central nervous system, the one thing they all have in common is the brain isn't getting enough energy from glucose. And another way of saying that is the one thing all of those seemingly unrelated brain problems have in common is that they all have some degree of insulin resistance. But, then it's no surprise that they all benefit when ketones can swoop in to save the day. Um but that only can happen if the person is giving their body a break from the insulin long enough to actually start making ketones. Really, really interesting on this point about Alzheimer's because I don't think people have spent enough time talking

59:10 about the link between insulin resistance and Alzheimer's. Um and one of the things I was I was looking at there was how many people with Alzheimer's have meet the criteria for insulin resistance. And some studies have it at 40%. There's a study I found here that has it at 70 to 80%. Um which I wanted to cite. Um Exact percentages vary, but one example is a study in the Journal of Neurology in 2011 that found insulin resistance at approximately 40% of individuals with Alzheimer's. Um but another study uh in Alzheimer's patients sometimes found it to be as high as 70 or 80%. For instance, research by Dr. Suzanne de la Monte Mhm. at Brown University has drawn attention to the concept of type 3 diabetes.

59:58 Yeah, again, I don't love the term, but I appreciate the use of it, which is it does suggest a metabolic origin. But even you look at those ranges, Stephen, you'd say, "Well, one was 40, one was 80. Boy, what a difference." I suspect a lot of that is just how did they measure insulin resistance? If they were looking at the glucose like so many do, you're just going to miss a lot of people. Yeah, it's quite hard to I think there's different criteria, right, for how one defines someone as insulin resistant. Well, there Yeah, and that's just that's right. That's because there's not enough training, which is at the beginning of the conversation you asked my mission. One of my missions is to help people learn what to look for. What do they need to be looking for? Yeah, they need to be looking at insulin. So Is that easy to measure? Well, it is technically easy to measure. It's just that we have we don't have enough systems in place to allow to

1:00:43 enable it. Like again, if if someone listening in the UK were to go to their GP and say, "Can you measure my insulin?" In many instances, they literally can't get it done. The system just isn't in place to take it to the lab and and measure it. Now, some do. I know some physicians in the UK who do so, and they have developed their own way of getting it done, and they're incredible advocates of this whole idea. But it is harder in the UK and Canada um where the system is such that they have said, out of ignorance, but perhaps well-placed or or well-intentioned, they will say, "Well, insulin isn't a marker that matters." It is. And if you're measuring insulin resistance, just to put things back to where we had talked about it earlier, many people with insulin resistance have normal blood glucose levels. It's the

1:01:30 insulin that's high. And so, I would say if a person can get their insulin measured, get it measured. In US units, if it is anything above about 10 micro units per mil, that's a warning. In UK units, if it's anything above about 40

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