Speaker 1When 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.
Speaker 2That's horrifying. So tell me everything.
Speaker 1Dr. Benjamin Bickman is a leading metabolic scientist whose 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 U.S. 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. There's the insulin resistance. So there's the fast lane. And I could make you insulin resistant in six 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 tackle this off and just take a Zampac? 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.
Speaker 2Holy s**t. 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 Diary of a CEO, 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. Benjamin, what is the mission that you're on?
Speaker 1My mission is to help people appreciate that much, that much of chronic disease. We look at them as these siloed, individual, distinct disorders with totally distinct origins, and yet much of them 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 then say, OK, there are, in 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 heart disease to type 2 diabetes to liver failure, fatty liver disease. All of them share a common metabolic core. That's my mission.
Speaker 2And what is that common metabolic core?
Speaker 1Yeah, 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 was this concept in the early 2000s that was really getting a lot of attention. Diabesity, this kind of dual epidemic of, wherever we see obesity, we see more type 2 diabetes. In 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 essentially, coming to the conclusion that, you know, there's 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 cause of hypertension. They call Alzheimer's disease type 3 diabetes, or more accurately, 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.
Speaker 2I 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? Oh, yeah, for sure.
Speaker 1Insulin 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 think of one side just because we hear the word insulin resistance, but there's another part to it that I need to, it's 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 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, 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.
Speaker 2So I eat sugar.
Speaker 1You 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. 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 is 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 smaller blood glucose or blood sugar response. But then. And if blood sugar is too high for too long, that becomes very harmful to the body. So insulin comes in and helps lower the blood glucose. And then having done its job, insulin comes back down.
Speaker 2So insulin comes out like a taxi and transports all the glucose in my blood to various places around the body to store them.
Speaker 1Perfect. Yeah. And the main. Yeah, that's right. You can sit. Look, 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 come and bring the sugar in via taxi. However, other tissues 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. But even on those like the liver, for example, if the liver sees sugar driving by in the 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 of 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 at the entire body is to tell the body what to do with energy in all of the cells. What to do with all of its forms as these kind of caloric rich molecules, what to do with lactate, what to do with ketones, what to do with fats or glucose, what to do with amino acids. So insulin will tell the body what to do with all of those things. But again, its most famous effect is to control blood sugar. And that's not wrong because its most powerful activator is blood sugar. So with all of that in mind, insulin resistance is two problems wrapped into one. The 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.
Speaker 2So say that again. So the. Yeah. Insulin's coming past with the glucose inside it.
Speaker 1Well, 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 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. And normally the muscle will say, oh, yeah, sure. Okay. Open it up the doors and let the sugar come in. When the muscle is insulin resistant, the bouncer's 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. resistance of what we call insulin resistance where some of 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 is 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 and i'll i'll mention an example in just a moment that highlights the difference between the two but we have to consider any time we talk about insulin resistance we think of two things happening you 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've 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 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 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, earlier at the outset of the conversation, I mentioned that even infertility has an origin, has some degree of development because of insulin resistance. And it's a perfect example of both of these parts of insulin resistance, where 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 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 the 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 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 lot of stuff. Insulin does a lot of things. Again, including telling blood vessels to expand. Now, unfortunately, in the case of 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 dysfunction.
Speaker 2I don't want to be insulin resistant. No. No one does.
Speaker 1No one does.
Speaker 2So tell me how it happens.
Speaker 1Yeah, 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 roads that 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. 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 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 six 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 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 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 when you're feeling a little stressed. Especially adrenaline slash epinephrine that are making you feel a little jittery. It's making your heartbeat a little faster. You're a little more alert. That all starts to play into a stress response. But what those two hormones have in 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 because 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 the body has those stress hormones elevated because of, say, sleep deprivation, that's a very effective way to increase cortisol. Or they are drinking too much caffeine. That is a way to increase epinephrine quite strongly. If both of those signals are too incessant or 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 and I were commenting about earlier about how, boy, there's a cold going around. It's flu season. Even then, if a person were wearing a continuous glucose monitor on the back of their arm, measuring their blood 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 is having a harder time keeping the blood glucose levels in check. Any time 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 joints are achy because 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. Insulin 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 door of the muscle cell. If one bouncer wasn't enough or one molecule of insulin wasn't enough, the body will say, well, let's send. There's 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, a cell, if it's capable, we'll 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 said 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 because I'm working during the day. And so when I hear that, it's a very fresh signal to 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 less sensitive to it than you were before we started. But again, as I 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.
Speaker 2If we can take it away. But if we can't take it away, does it become sort of chronic?
Speaker 1Yeah. So 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. 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 it's cereal or it's bagels. And it's going to be a very starchy, sugary breakfast. And it's going to be a very starchy, 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 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. 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 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, I'll do this in kilos for the UK audience. Steve has 10 kilos of fat on your entire body. That's probably too much for you. Ben has 20 kilos. And yet. It's possible that I'm healthier metabolically than you. 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 in 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. But the bigger the fat cell gets, the more it initiates a cascade of events or a series of events that creates insulin resistance.
Speaker 2And am I right in thinking we have the same amount of fat cells for our whole life, pretty much?
Speaker 1That's a really, really safe assumption for most people. Yeah. For most people, a fat cell, 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. 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.
Speaker 2This is something people don't really understand. And this is something that we've actually discovered 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, expanding.
Speaker 1Exactly. That's exactly right. Now, there are differences across.
Speaker 2Which, by the way, makes liposuction a pretty fucking bad idea.
Speaker 1In fact, it makes things worse. Please, let's make sure we come back to that.
Speaker 2Okay, I'll write down liposuction.
Speaker 1Because it really becomes. The person ends up. I don't know. I don't know. I don't know. I don't know. Their vanity ends up really ruining their future metabolic outcomes. But there are differences across ethnicity. This is a little oversimplified, but not much. On one end, you'd have Caucasians, kind of Northern European Caucasians. On the other end, you'd have East Asians, like Chinese, Japanese, Korean, East Asians. And then if you look at that same spectrum of people making fat cells, and then stop right about here.
Speaker 2About sort of.
Speaker 1So 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 here we are. 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 I could. Be the same percent body fat, really, as Chinese Ben. 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, which as a pasty Caucasian, he's not going to look particularly good in that way. But I just am bulging a little more than I was before. But otherwise, I'm healthy. My blood pressure is fine. My blood sugar is fine. Everything's normal. Put that same 10 kilos of fat on Chinese Ben, hypertension, type 2 diabetes, fatty liver disease, infertility. 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 cell promotes insulin resistance very, very readily. And so that logically moves into the question of, well, 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 impossible 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 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 the fact that this exists is absolute proof that the growing and the shrinking of the fat cell is more complicated than just calories being high or low. Because like I'd said earlier, when I talked about hormones, hormones are a way for the very tissues of the body to grow. 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. Or maybe to make this more direct, back home in my lab, 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 four hours later, they're immediately fatter. If we check them four hours later, they're immediately fatter. 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 oh very much now if you so so a moment ago i said that the big fat cell is 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 because 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 keeps the fat cell from growing so the insulin signals 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
Speaker 2you'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 so 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
Speaker 1yeah yeah so so your body now it would partly depend on there are people where you you if you're 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 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 a thousand calories in one meal one version of this is the conventional way of eating which is lower fat higher carb and that's the same thing the other meal same number of calories 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 someone would say well where do the calories go you can't 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 of eating you're going to have a lower insulin response and you're going to have a lower 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
Speaker 2rate is that yeah that's
Speaker 1the total amount of energy that it just costs you and i to just live okay so we're just 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 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 don't intend to get onto that topic quite yet but suffice it to say every molecule of a ketone has a as a caloric load roughly similar to glucose and one of the 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 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 in the form of ketones because ketones have calories ketones are energy now we're just dumping them out into the universe
Speaker 2it'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
Speaker 1theories 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 what was the difference that had us become so different than them one of the leading theories 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 us to eat more meat and we started eating more meat and we started eating more meat and we started eating more meat and we started eating more meat and we started eating more meat two very distinct changes to occur in us compared to other primates one our intestines became significantly shorter so if you compare the human digestive tract to any other primate animal if we are a primate 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 colon as much because the colon is the largest intestine and the colon is the largest intestine 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 it allowed us to have more time to be curious and explore and so at the same time our intestines became more and more and so at the same time our intestines became more and more 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 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 fast straight for two days if you took a six-month-old baby that baby would be in a deeper state of ketosis in two hours than you and i would be in two 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 when 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 this idea which if if to use some convenient uk units if blood glucose is five millimolar that's a concentration a way of measuring an amount of of something blood glucose may be five millimolar or 80 milligrams per deciliter for the american audience 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 one 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 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 when it doesn't get them interesting i mean that's
Speaker 2a controversial thing to say it is and you
Speaker 1can cut but it really is it's a real thing and why does depression and go up so much when people stop eating animal source foods it's because you are depriving the brain of what it
Speaker 2needs what is it exactly you're depriving the brain of in that
Speaker 1situation 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 yes 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
Speaker 2so is that the the only evolutionary sort of hypothesis towards why we develop this insulin
Speaker 1resistance 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 the body is deficient in insulin resistance so it's a way for the body to know when the body it was needed to hold on to energy a little better so now i say that now 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've been talking about is pathological insulin resistance or harmful insulin resistance insulin resistance that serves no good purpose 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 muscle and bone but also including fat so in
Speaker 2pregnancy insulin's playing a role in growing the placenta it sure is the breasts yeah so in the
Speaker 1woman after she's finished puberty insulin's playing a role in growing the placenta it sure is the breasts yeah so in the woman after she's finished puberty insulin's playing a role in growing the placenta it sure is the breasts yeah so in the only other time of growth she'll ever have will be pregnancy 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 oh 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 as her body becomes insulin resistant it actually facilitates the growth of the baby a little more rapidly but as you noted it helps her store more fat and progesterone is another hormone that even accelerates that process but basically it's 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 of pregnancy so it's perfectly timed question because if you look at the average woman 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 and then in some women especially if she has a family history of type 2 diabetes the insulin resistance goes too far 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
Speaker 2eating loads and loads of sugar throughout a pregnancy
Speaker 1that 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
Speaker 2does that then impact the future baby oh for
Speaker 1sure it does yeah so think about it's almost like the baby is developed literally developing in a hyperglycemic hyperinsulinemic environment so the baby's the baby gets hardwired to want to continue to exist in a state of high insulin and 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
Speaker 2your book that these infants have a 40 percent higher chance to be obese and have metabolic complications in their teenage years
Speaker 1and beyond yes i mean a significant thing and i i say that with all of the sympathy i can for the fact that if you have diabetes you're not going to be able to have a baby if you don't have a baby
Speaker 2you're not going to be able to have a baby you're not going to be able to have a baby you're not going to be able to have a baby you're not going to be able to have a baby you're not going to be able to have a baby you're not going to be able to have a baby you're not going to be able to have a baby you're not going to be able to have a baby you're not going to be able to have a baby you're not going 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. this is cancer incidents by age and gender up to 49 years old. And I was wondering if you had any thoughts on why this is happening.
Speaker 1Yeah, yeah. Yeah, a few thoughts come to mind. Whenever I see these kinds of reports, I always make sure I look 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, 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 exciting answer, this is very, very likely almost entirely driven by breast cancer. Breast cancer is the main cancer for women 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, 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, very well documented, that if a woman has babies and breastfeeds, her risk of breast cancer goes down. So, yeah, in fact, it's very meaningful. I actually don't know the reasons for it. It could be the changes in estrogens during lactation phase.
Speaker 2I'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.
Speaker 1Oh, yeah. I promised I was going to talk about that. I wouldn't leave that.
Speaker 2Sorry for interrupting there. No, no, no problem. And then the other one was delayed childbearing. That's what I'm saying. Which is what you were saying.
Speaker 1Yeah. So as childbirth rates are going down, it does increase the risk of breast cancer. a baby you're not going to have a baby you're not going to have a baby you're not going to have a baby and 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.
Speaker 2As 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 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 of Whoop, said, 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 slash CEO and try Whoop for 30 days, risk-free and zero commitment. That's join.whoop.com slash CEO. Let me know how you get on. You know, one of the big subjects you touched on at the start 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 3 diabetes. Worldwide, there is a new case of dementia every 3.2 seconds. It seems like, I don't know if this is true, but is Alzheimer's and dementia on the rise?
Speaker 1Oh, yes. Yeah, it is. In fact, it went from not being even on the radar to being at top. Top 10 killer. 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, certainly in the West. And I would argue it's because it has a metabolic origin. One of the interesting things about Alzheimer's disease is we have spent billions of dollars on Alzheimer's research trying to identify the plaque. So just to set the stage here so that people listening to this can appreciate 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 have normal cognition. And yet, there are those of us, and I'm 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 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 post-mortem or look at tissue donor people who'd 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 whether the brain had Alzheimer's disease or 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 metabolic origins, about two or three years ago, they found out that the plaque-based theory of Alzheimer's disease was the result of a study that was published in the New York Times. 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 indeed, all of it was fabricated. So the entire idea that Alzheimer's—and we have spent billions of dollars on studies to try to determine how do plaques cause cancer, 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 these little specks than other brains, and they don't contribute to Alzheimer's disease at all. Now, 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 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 a trinity of high metabolic rate organs, 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 needs 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 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 know, mind the gap. And the brain has an energy gap now. And it's not just the ketones that are filling the gap. It's the ketones that are filling the gap now, 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. And so 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 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 use people with the 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 it. Migraines have a brain glucose hypometabolism to it. And so you can see that the brain is not getting as much hypometabolism epilepsy um and parkinson's disease 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 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
Speaker 2interesting on this point of alzheimer's because i don't think people have spent enough time talking about the link between insulin resistance and alzheimer's um and one of the things 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 percent there's a study i found here that has it at 70 to 80 percent 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 percent of individuals with alzheimer's but another study in alzheimer's patients sometimes found it to be as high as 70 or 80 for instance research by dr suzanne de la monte at brown university has drawn attention to the concept of type 3 diabetes?
Speaker 1Yeah, again, I don't love the term, but I appreciate it. appreciate the use of it which is it does suggest a metabolic origin but even you look at those ranges steven you'd say well one was 41 was 80 boy what a difference i suspect a lot of that is just how did they measure insulin resistance right if they were looking at the glucose like so many do you're just going to miss a lot of people
Speaker 2yeah it's quite hard to i think there's different criteria right for how one defines someone is insulin resistant well
Speaker 1yeah 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 they need to be looking for yeah they need to be looking at insulin
Speaker 2so is that easy to measure
Speaker 1well it is technically easy to measure it's just that we have we don't have enough systems in place to allow it to enable it like again um 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 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 where the system is such they have said out of ignorance but perhaps well placed 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 pressure and they don't have insulin resistance blood glucose levels it's the insulin that's high and so i would say if a person can get their insulin measured get it measured in u.s 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 picomoles that's a warning insulin is high you could have insulin resistance and
Speaker 2you could be skinny oh yes and have insulin resistance
Speaker 1yes that's especially depending on the ethnicity like if someone listening to this is east asian and they say well i'm quite thin i don't have insulin resistance you very well could um it depends even in in young women a group out of northern canada which is of course pretty far north they found that even in young healthy weight women with pcos they if they compared them to their identically matched other women without pcos they were more insulin resistant in the other group so so anyway that's my way of saying even if you look at yourself and think well i'm not insulin resistant you very well
Speaker 2could be okay so i've got a friend who's a woman who has pcos yeah and one of the things that she often says to me is that she gains weight easily is
Speaker 1this true oh for sure and in fact i wouldn't be surprised if she does because the fact that she has pcos is not absolute evidence but very likely evidence that she has insulin resistance which would mean at any given moment her insulin is at the risk of being a little higher than her non-insulin resistant counterparts so if she goes and gets the test done i bet her insulin would be high um and so all that would mean is which is good i mean knowledge is power and my hope would be that as someone goes and gets their insulin measured and there are a handful of other tests they could also look at but that's the most succinct then it would be all the more impetus or encouragement to say okay i heard i listened to steven and ben i really do need to start making some changes and even in pcos there are reports that document the absolute reversal of the disease with nothing more than just dietary changes i was looking
Speaker 2also a second ago because we mentioned ethnicity a few times and it says the research i was looking at says that east asians have east asians have fewer fat cells and they're more resistant to obesity related metabolic issues
Speaker 1well that's second part of that statement is not true they're more resistant to obesity but they are like if it's an interesting dichotomy because okay i got you yeah so they're
Speaker 2more resistant to obesity but they're more resistant
Speaker 1you like to find a japanese man who's as fat as the average american boy you're gonna have to look it's hard it's hard but to find a japanese man who has is just as much likely to get diabetes type 2 diabetes very easy
Speaker 2africans have more fat cells typically yeah so
Speaker 1so on that ethnicity if now there's a lot of kind of wiggle room here but on one end we'd have caucasians blacks would be right nearby african ethnicities would be quite close um to the to the caucasians but on the other hand kind of northern european ethnicity and then we would move through and i don't mean to miss anyone here but on the other end it would be east asian and then sprinkled through that would be um uh latino latino would be somewhere in the middle and hispanic and then other southeast asian and east asian kind of on the worst end or the least sensitive or the most sensitive to their fat the most sensitive to their fat this actually is a concept that has been presented called the personal fat threshold which is this really interesting idea born from a group in australia suggesting that across every individual body which of course is heavily influenced by both ethnicity and sex like we'd mentioned earlier a body is going to have a rate at which it can store fat in a healthy way and then once that threshold is met any further pressure to store fat will start creating insulin resistance and that threshold is essentially how big how many fat cells do you have and how much room do they have if you have more fat cells you have a higher fat threshold you can get fatter before it starts to
Speaker 2hurt you does your fat distribution also matter here because it does different yeah races this research is telling me have different fat distribution it's saying that africans have better fat distribution lower visceral fat and less metabolic risk because of that yeah yeah yeah caucasians moderate fat cell quantity more prone to subcutaneous fat accumulation which is subcutaneous which is that's the fat around the organ yeah so
Speaker 1caucasians and so so let's say northern european african both store more of their fat subcutaneously which is the fat just beneath the skin or the fat that you can pinch and jiggle that has an ability to expand more because there's nothing really to limit it um however the other place for people to store fat is their visceral adipose which is the fat that is tucked within the abdominal cavity so tucked around the organs it's sort of surrounding the kidneys and the intestines and the liver that is an unhealthy place to gain fat but an unhealthy place to gain fat and that's why we're going to talk a little bit more about that in just a few minutes because we're going to talk about that in just a few minutes east asian all things equal is putting much more fat there than they are subcutaneously the advantage of subcutaneous fat is which is the fat on the outside yeah yeah so the the fat beneath the skin yeah the yeah the loose belly fat the fat that can pinch and jiggle that fat has a greater ability to make new fat cells so as much as earlier you and i said fat cells remain static for the most part they do there's a little bit of wiggle room where it can go up and that's purely subcutaneous and
Speaker 2hispanics have higher fat cell quantity more visceral fat yes and increased risk of obesity
Speaker 1related conditions yes and so the problem with visceral fat is this is such a finite space there's so little room within the core of your body that if we allowed those fats to multiply it could theoretically start physically compressing on tissues right and so those fat cells only grow through hypertrophy which is the thing we talked about earlier with slow insulin resistance subcutaneous fat cells are more abundant but smaller visceral fat cells are fewer but much larger and so any ethnicity including hispanic or asian that promotes relatively more fat storage in the visceral space is going to suffer from the consequences of that fat much sooner and again it still comes back to size the bigger the fat cell the sicker the fat cell according
Speaker 2to alzheimer's disease international the total number of people living with dementia globally is expected to reach 139 million by 2050 which is up from around 50% of the world's population and that's a lot of fat cells in 2020 which i imagine is in part related to people living a bit longer yeah they want it as
Speaker 1well although all over the past few years life expectancy actually turned down for the first time in the history of modern world so who knows if it will continue to go up but yeah it could be people are living longer i mean one of the effects of modern medicine is that people live longer with disease um alzheimer's included but it's absolutely a consequence further of our metabolic milieu that we put ourselves in a position where we're making our brains insulin resistant and thus they're going hungrier and hungrier
Speaker 2there's a study you talk about um which you've cited before that shows that if you move visceral fat from an obese animal to a lean animal this immediately caused insulin resistance
Speaker 1yeah in the animal that received it okay yeah so just to be clear if if we took what they did in this study just to reflect or the different depots of fat are harmful and so the human body has two distinct fat depots and you and i described them subcutaneous which is the fat beneath the skin or visceral which is the fat tucked within the organs of the abdominal space and if you move subcutaneous fat which is like the belly fat the belly fat and from one animal to another you couldn't do this in humans if you move belly fat if you will or subcutaneous fat from one animal to the other the animal is very healthy it's no problem subcutaneous fat is inert it really is just sort of hanging out there and minding its own business but in that same study if you move the visceral adipose over now all of a sudden that animal that got that extra dose of visceral fat is going to become sicker it's going to become more insulin resistant and diabetic because you've increased its visceral fat the amount of fat that it has in that space the body wants to limit the amount of fat that it has there because if the fat again if the fat grows too much you can physically start compressing the fat and it's going to become more and more and squishing organs that you need functioning like the kidneys and the intestines have you seen brian johnson i have i don't know him personally but you've seen
Speaker 2the documentaries and stuff made about him in the work that he's doing what do you make of what he's doing to extend his age because you know one of the subjects i think is linked to this is the idea of longevity yeah in aging and he's become a bit of a poster child for the subject of longevity
Speaker 1right right well i want to address this because this is a real person so i want to address it very politely and diplomatically i think that i want to distinguish the difference between longevity research and science which is a very real living breathing field and i'm proud to know individuals who are longevity scientists and distinguish them from um longevity you said poster child so the the gurus of longevity and that's not the same thing so what i say i don't mean to it to be an indictment of longevity research but i don't mind if people hear a bit of an indictment in my voice of the modern longevity guru approach so these individuals and he is certainly the most um well known they do have the advantage of never really being able to be proven wrong you know so there's an inherent problem here but i will say that the the application of being a longevity um expert or not a scientist but a guru and i don't mean for that to be negative but it does have a bit of a negative sound to it is that you have to rely on what i would call weak evidence now what do i mean by that so all of the approaches to longevity nowadays rely on either correlational studies or basic research or animals and insect studies and then extrapolating that results or assuming those same results will apply to the human so let me briefly just mention my concerns with correlational research so the longevity guru will say correlational evidence suggests that people who eat meat um die more and that's not the case with longevity well a correlational study is by my estimation some of the weakest evidence that you can ever generate a correlational study would just have someone come to your home and say steven can you please answer this survey about what you eat you answered the survey you may lie you may not remember you may have things that you don't even think about including like for example that you're part of a very um well put together religious organization and i actually use that example very deliberately because people who are known to be part of good tight social circles like a formal religious group always live longer than people who don't maybe you're really lonely loneliness is a greater contributor to death than cigarette smoking and it's not even close so there could be things on that survey that you just cannot capture and yet we end up making a conclusion and so all of that correlational evidence is deeply flawed research and yet that becomes the basis for the longevity guru to be able to do that so i think that's a great question and i think that's a great question to determine diet
Speaker 2so if i'm trying to extend my longevity yeah trying to live longer then exactly what should i be thinking
Speaker 1about yeah so my view on longevity is a metabolic view no surprise i'm a metabolic scientist and i don't mind someone sort of smirking at me declaring that or admitting it but i'm somewhat justified just by way of setting the stage the earliest the birth of the influenced by the work of a woman named cynthia cynthia kenyon k-e-n-y-o-n cynthia kenyon was one of the kind of she really did in my mind kind of give give birth to the modern longevity focus what her lab found using an insect model and this is again a problem with the longevity gurus is that they rely on insect data for example but it was compelling what she found i think it was worms she found in worms that if they were shocked by the longevity gurus they would be shocked by the longevity gurus they would be shocked by the longevity gurus they would be shocked by the the glucose that the worms were eating they would live 50 percent longer or some some fantastic increase in the how long the animals lived that kind of gave birth to the idea of fasting being beneficial but it also allowed her lab to start playing around with some of the genes of these little insects and when they started knocking down or under expressing some of the genes involved in insulin they didn't have to restrict the food the animals just lived longer and so that touches on this metabolic aspect and everyone nowadays is really interested in autophagy autophagy is a term for a cell essentially cleaning itself out which is
Speaker 2typically associated with long
Speaker 1fasting yeah that's yeah yeah in fact yes so that is partly why fasting has been so embraced within the longevity community it's because if you can promote longevity or autophagy rather if you can that is thought to be a key contributor to longevity so autophagy equating to longevity i don't disagree with that i think that probably is a very valid view then the question comes well how can i control autophagy well there is a humble hormone that comes from the pancreas that has a very powerful effect on autophagy called insulin so as much as people are fasting what's the value of fasting and reducing autophagy it's because insulin comes down now what becomes interesting is what happens if you were to put someone allow them to eat calories but the calories are such that their insulin is staying low and they're making ketones in other words a ketogenic diet you also enable autophagy there was a very well done animal study finding that they didn't have to restrict calories and fast the animals they could let the animals eat as much as they wanted but it was a ketogenic diet they lived significantly longer than their other litter mates that were eating the normal high carb chow similar to what humans eat nowadays and so autophagy probably does matter for longevity all the more reason to keep your insulin in check because insulin is a powerful inhibitor of autophagy so as much as we have longevity gurus who are taking thousands of dollars worth of supplements i can't help but look at that and think just control your insulin that within every cell there's this battle there's a yin yang of growth and death or building and breaking to say it a little more politely in fact that is metabolism the very word metabolism encompasses anabolism which is anabolic or building up and catabolism or catabolic which is breaking down the key to a healthy growing living cell is this nice ongoing balance of build and break build and break you have to build something up and then modestly break it down and then you build some things up again and autophagy is a very important part of that breaking cycle within the cell that hey it's time to get rid of some old parts and now we'll rebuild some of that again now we're going to break down these parts and rebuild it insulin is the key to that process if insulin stays high for too long you never allow the catabolic or the breakdown this is one reason why insulin is so facilitative to cancer insulin wants things to grow cancer is a disease of growth we don't ever let the cancer start to break down insulin won't let it in part
Speaker 2you've um repeatedly talked about ketosis i have we'll eventually get there we're kind of teasing the audience a little bit yeah
Speaker 1we are yeah but rightly so i mean ketones are a very vilified misunderstood part of the body and to my great delight um it's getting it's getting a sort of
Speaker 2new appreciation well i'm currently on the keto diet as well so i am incredibly interested to understand a like what's going on in my body but b i i'm quite compelled by both the pros and cons of doing it and i want to talk about the cons and the pros um because they both exist one thing you say in your book why we get sick is that the longest living humans are also the most insulin sensitive yeah so you're telling me that the longest living humans are the ones that are able to stave off that insulin resistance yes yes there are keep their insulin levels
Speaker 1lower that's right yeah in fact most of the longevity research was sort of a final point on this um is that when you look at these studies that look back in time and say okay what is it about these people that are so insulin sensitive and that they're so insulin sensitive people what variables tend to go along with the longest lived humans one of them is that they're insulin sensitive and their blood glucose levels are in fact a very well done study just last year out of sweden i think it was just one year ago they looked at all and sweden is meticulous in its in its record keeping which is an advantage in a fairly homogenous society so it kind of eliminates some confounding variables but they attempted to document what were the variables that were just the most consistent and the most consistent and the most consistent and the most consistent theme of people who lived very long one of them was good glucose control and this next one is very controversial because they found that they also the longest lived people had high cholesterol levels and isn't that funny it is one of the most consistent themes of longevity research that the longest lived people have higher cholesterol and yet we live in a world that hates cholesterol and the moment cholesterol goes up we put them on a cholesterol lowering medication we could be doing the perfectly wrong thing to help these people live longer so that was and then low uric acid and there's a handful of other little variables that fit into
Speaker 2this sorry they found that some of the longest living humans had high cholesterol levels that's
Speaker 1right that's what the sweden study found for example the paper just published a year or so ago what were some of the most consistent themes they had good glucose control and high cholesterol i'm a great defender of of cholesterol it is a molecule of life and it's so many so much depends on it mitochondria for example. Mitochondria have to have a cholesterol molecule in their them in order to work, like the very powerhouse of the cell. And the more you lower cholesterol through, say, drug interventions, the more you compromise the mitochondria. The sex hormones, all sex hormones are built on cholesterol. It's no surprise if someone takes a cholesterol-lowering medication, their sex hormones go down. This is why some men experience such terrible loss of libido, because he's becoming low testosterone because of the war on cholesterol.
Speaker 2But it's good and bad cholesterol, right?
Speaker 1Well, that's, as the story goes, yes. And yet I think that's overly simplified, where people will say LDL cholesterol is the bad cholesterol. And yet that gets included in these studies of longevity. So I think the good and bad aspect of it is not entirely fair or accurate. We need LDL. And LDL is just as much a component of the immune system. LDL actually helps the body fight infections. So it's also an unsung hero of immunity.
Speaker 2There is research suggesting that LDL is a good and bad cholesterol. In very old age, high cholesterol levels do not always correlate with higher mortality. And in some studies may even be linked to longer life. Exactly. Which is bizarre.
Speaker 1Yeah, well, you say that, and yet maybe our anti-cholesterol view is the bizarre one. Yeah. And so as a cynic who's very familiar with biomedical research, I sometimes will look at clinical markers and say, why are we so obsessed with glucose? Why not insulin? Why another lipid that can be measured that is far more predictive of who's going to have a heart attack or not. And I think it's because we have chosen markers in modern medicine that we have well-designed drugs. So it's a really, really good way to sell a lot of drugs. So there's no drug that's going to address insulin. So let's not measure it. But there are lots of drugs that will lower glucose. So let's measure glucose because then we can diagnose the problem and then we can give them a drug and make a lot of money. That's a cynical view, but I don't think it's unjustified. Similarly with cholesterol. Why look at LDL when triglycerides, another lipid marker, are a much better indicator? It's because we don't have a drug that effectively lowers triglycerides. You can with diet, but we do have drugs that very effectively lower LDL.
Speaker 2One thing that really surprised me when I was reading your work is there was a study done in Bulgaria, which proved that smoking. Smoking causes insulin resistance in humans by having seven healthy non-smokers smoke four cigarettes over an hour for three days. What did they find in that study?
Speaker 1Yeah, so they found that if you took healthy non-smoking people and had them start smoking, they became insulin resistant. I believe I invoked that study in the section where I was talking about inflammation, where when you cigarette smoke, there's a lot of junk coming in and there's a powerful inflammatory response and that contributes to insulin resistance. It's vaping as well. Oh, that is a very good question. I have, in fact, published now multiple papers with a very good friend and colleague who is a lung expert at my university, a guy by the name of Paul Reynolds. Paul and I, we have published reports together looking at cigarette smoking and the inflammatory and insulin resistance effects that come from that. And now we've even started looking at the molecules, the hyperheated molecules from vaping, and they're terrible. In fact, yes, very similar results. If you were to take a comparable amount of the chemicals from normal cigarette smoke with its filter versus vaping, the vaping ones are probably worse, chemical for chemical. In terms
Speaker 2of their insulin?
Speaker 1Yeah, in terms of their inflammatory effect, the damage to the airway and the insulin resistance that comes from it. That's horrifying. It is, in part because of just how common it's become. Does smoking make us fat? Oh, that's a great question. It doesn't because it replaces other interests. So if the cigarette smoker ate the way everyone else was eating, it would. But because the cigarette smoke satisfies a craving, they have less of an interest in food. What's so interesting about cigarette smoking is, again, as I said, you begin to smoke, other things don't tempt you as much, like the cookies and the cakes. But one of the ways the smoker helps kick the habit of cigarette smoking is actually eating candy. They will literally start carrying around little candies in their pocket. So if they feel a craving for cigarette smoking, they will take out a little candy, open it up and pop it in their mouth. And so it's no surprise that very commonly, when a person quits smoking, they gain significant weight. They end up trading out their addictions, if you will. And unfortunately, in humans, all of the study of addictions with food, people only manifest an addiction to one type of food, and that is carbohydrate. There's no evidence of addiction to fat, but there's no evidence of addiction to fats or proteins.
Speaker 2You published a study in 2024, which found that exposure to diesel exhaust gas was associated with increased fat mass, enlarged fat cells, insulin resistance, and increased levels of inflammation. And that was published in the International Journal of Molecular Sciences.
Speaker 1Yeah, that was one of the studies I just was referring to with regards to my colleague, Paul Reynolds. Paul and I, that was one of the papers we published, looking at these inhaled particulates. The reason I was interested in this field of study in the first place was just to continue to kill the caloric model of obesity. So, and this touches on an earlier part of the conversation. Overwhelmingly, if you ask someone, why do we get fat? Well, because you eat more calories than you burn. Why do you lose fat? Because you eat fewer calories. And I have long just been frustrated by how naive that view is. Yes, energy matters, but again, the fat cell must be told what to do with the energy that it has. That, of course, points an obvious finger at insulin, which is the strongest of all. And I think that's a good point. I think that's a good point. All signals. But what we found in that study is that even something as seemingly unrelated as diesel exhaust particles, mind you, we did not do this study in humans. Full disclosure, we did the study in animals where we could perfectly control how much diesel exhaust they're getting. So we have this mechanism through, in Paul's lab, where you can aerosolize these particulates and know exactly how much the animal's breathing. And then at the end of the study, after, even though they ate the exact same amount of food, the animals that were exposed to the diesel exhaust, particulates, had fatter fat cells and more insulin resistance than the animals that had just been breathing normal room air.
Speaker 2So what we're breathing in, theoretically, could then be determining how fat we're getting.
Speaker 1Yeah, in fact, this evidence would suggest that it goes beyond theory. So our evidence would state conclusively that yes, what you breathe does matter. Then theoretically, we would say, well, how much does that apply to humans? That is where it would get into the realm of theoretical. But the evidence certainly suggests, yes, the very air we breathe matters. And you can't just say, well, how much does that apply to humans? That is where it goes. You see this at a population level. Look in areas where there are, now, there are confounding variables here. Here I am invoking correlational research, and I was just criticizing it a moment ago with regards to longevity. But you look in areas where they have higher pollution levels, where the particulates are higher in the atmosphere, and those same areas are always fatter and more diabetic. Interesting.
Speaker 2But of course, that's
Speaker 1correlational, so it's hard to. I think we're citing the problem with the correlational study there. We need to always cite the problem with correlational studies when it comes to informing nutrition policy, like don't eat eggs because they cause diabetes. But when you actually look at the studies, you find nothing of the sort.
Speaker 2What about other sort of environmental toxins and their impact on insulin resistance? Yeah.
Speaker 1So there are the ones that you inhale. A handful of inhaled particulates will matter. We have shown in my lab alone with my collaborators, diesel exhaust will do it, cigarette smoke will do it. And we have a funded grant right now to look at the effects of vaping. So apparently, stuff we breathe will matter. To some unknown degree, things that we drink will that are non-caloric. So there can be. People have heard of the microplastics. Microplastics are things that you can't. They're so small that you drink them, and they will absorb through the intestine and get into the bloodstream. For reasons that are unknown to me at the moment, one of the sites where those microparticles will go is the fat cells. And once there, they will directly promote the growth of the fat cells. So that's actual microscopic segments of plastic. But separate from that are molecules that can come from plastics and soaps and detergents like BPA or diethylstilbestrol, DES. That's actually an estrogen mimetic, kind of what we referred to earlier with regards to other endocrine disruptors. But there are other chemicals that a can inhale, like I mentioned earlier, but that will directly impact the growth of fat cells or mimic what insulin wanted to do, which is tell the fat cell to grow.
Speaker 2I've invested more than a million pounds into this company, Perfect Ted, and they're also a sponsor of this podcast. I switched over to using matcha as my dominant energy source, and that's where Perfect Ted comes in. They have the matcha powders, they have the matcha drinks, they have the pods, and all of this keeps me focused throughout a very, very long recording day, no matter what's going on. And their team. is obsessed with quality, which is why they source their ceremonial-grade matcha from Japan. So when people say to me that they don't like the taste of matcha, I'm guessing that they haven't tried Perfect Ted. Unlike low-quality matcha that has a bitter, grassy taste, Perfect Ted is smooth and naturally sweet. And without knowing it, you're probably a Perfect Ted customer already if you're getting your matcha at places like Blank Street or Joe and the Juice. But now, you can make it yourself at home. So give it a try, and we'll see if you still don't like matcha. So here's what I'm going to do. I'm going to give you 40% off our matcha if you try it today. Head to PerfectTed.com and use code DIARY40 at checkout. Or if you're in a supermarket, you can get it at Tesco's or Holland & Barrett or in the Netherlands at Albert Heijn. And those of you in the US, you can get it on Amazon. 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 think it really comes down to the most overlooked yet crucial feature. 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 let's talk about ketosis and ketones. The diet, the keto diet is becoming increasingly popular from what I've seen. It's actually the diet that I'm on at the moment. How does that play into everything we've talked about?
Speaker 1Yeah. Yeah. So this is an opportunity for me to do a little bit of nutrient biochemistry or a little discussion of metabolism so that people appreciate what ketones, ketones even are and where they come from. So the entirety of the human body is a metabolic hybrid in that the body is largely burning fuel from two sources. It is burning blood glucose or sugar, blood sugar, or it's burning fat. Those are the two main fuels for the body by extension. Now, the brain was an exception. The brain is glucose or ketones, but I'll get to where the ketones come from. The rest of the body isn't really relying on ketones as much. It's fats or gluten. Glucose or blood sugar. Insulin is what decides which fuel is used. So as much as the metabolic engine has two fuel sources, insulin will decide which one is opened and which one is closed. If insulin is high, the body is sugar burning. And you can measure this in the whole body level by measuring the amount of oxygen and CO2 that the body is producing because different biochemistry or the burning of the fuels will produce a different amount of CO2.
Speaker 2So if I'm burning glucose, I might be producing more CO2.
Speaker 1Yes. Yeah. So we could. We could hook you up to something called an indirect calorimeter and measure that your RER, the respiratory exchange ratio, the balance between CO2 and oxygen, would go higher. So we increase your insulin. Like if I infused you with insulin, in the next few minutes, we would see that your RER would go up and we'd say, boy, you're sugar burning. Or we allow insulin to come down and then the RER goes down, which is reflective of fat burning. So it's insulin that determines whether the body is sugar burning or fat burning. Now, when insulin has been low for about 16 or so hours, something interesting starts happening at the liver. So the liver, with insulin being low, is burning a lot of fat, including its own fat that the liver can store. The liver can store fat, but also fat coming from fat cells. Because if insulin is low, the fat cells are just leaking out fat to be burned by the body. And because insulin is low, the liver keeps burning it. And the liver essentially. Burns, continues to burn so much fat that it fills its own needs. It meets its own needs and says to itself, hey, I don't need to keep burning fat. I have all the energy I need. I'm doing great. But it can't stop burning fat because insulin is low. And if insulin stays low, fat burning keeps going. And so. Because the body doesn't have enough glucose. Well, it's acting. Yeah, so in this sense, it's doing it to help replace the glucose that isn't coming in. That's the value of the ketone. If the liver is continuing to burn fat, it essentially gets to a point of fat burning where it's burning more fat than it needs. And that excess, if you will, is what becomes ketones. So ketones are kind of a metabolic release valve for the liver cell to say, I can't. I don't know what to do with all this fat burning. Okay, I know what I'm going to do. There's not a lot of glucose coming in. And so the brain may start to get hungry. So I'm going to start making ketones. And so ketones are nothing more than a product. A product of a lot of fat burning. And anyone who even fasts for 24 hours, you wake up that next morning, you're in some degree of ketosis. Lest anyone think it's an extreme thing. People are going in and out of ketosis, ideally, often. Now, why do I say ideally? It's because ketones are, as we've already outlined, perhaps the best fuel for the brain. The brain thrives on ketones. You can take a person with early-stage Alzheimer's disease and have them go through a series of cognitive tests, and they do horribly on them. Like one example is you ask the patient with Alzheimer's to draw the face of an analog clock, a circle with 1, 2, through 12, and then some hands on it. And it is utter chaos. This is published reports. You then put them into ketosis, ask them, can you please draw the face of a clock? It's still sloppy, but it is absolutely the face of a clock. You ask them, when they're not in ketosis, to try to tie their shoelaces, they can't think through the puzzle of tying the shoelaces. Ask them to do it again when they're in ketosis, all of a sudden, they can tie their shoelaces. More than that, they can get themselves dressed. All of these are published case reports. It's just my long-winded way of saying the brain thrives when it has ketones as a fuel source. But the benefits don't stop there. My lab published a report finding that when humans were in ketosis, which is just a term for ketones being elevated, we pulled out small pieces of belly fat and measured the metabolic rate of that belly fat. And we found that in ketosis, the metabolic rate of that belly fat was three times higher than when the people were not in ketosis. What does that mean? Yeah, so that means that the fat was suddenly behaving in a much more energetic way. That fat tissue has a very low metabolic rate. And then all of a sudden, when the ketones came into them, they started getting much more active and they started burning more energy, which is going to be very helpful for someone who wants to lose fat. If your fat cells now have a three times higher metabolic rate, that means that the fat cells are starting to act a little bit more like your muscle cells and they're just burning
Speaker 2more energy. So does that mean that I'm going to lose fat faster?
Speaker 1Yes, absolutely. And that is what happens. There are very well done controlled studies to show that if you control for all calories, when a human is in ketosis, their metabolic rate goes up. Your body, your whole body is just burning more. It's just everything's kind of been turned on a little more. The, the, the, the furnace of the metabolism has just been, it's, you have a little more fuel kind of stoking the fire. So ketones will increase metabolic rate of fat tissue. We found a paper that we published documenting how we took muscle cells and kind of insulted the muscle cells to determine how tough the muscle cells were. When we incubated the muscle cells with ketones, they were much more resistant to injury. So the ketones act to protect muscle tissue. And in a way that is reflective of a function of ketones, ketones are a defender of muscle. Ketones are basically the way to tell the brain saying, brain, you think you need a lot of glucose. And if you don't get enough glucose, you would start stripping the protein from muscle to turn it into glucose. But I'm here as a ketone, so you can eat me instead and not, and leave the muscle alone. So we published again, a direct report finding that ketones actually make muscle more resistant to injury. And this could be why you're seeing more and more elite athletes using ketones as an actual ergogenic aid or like a supplement to help them better, be better. So at my university at BYU, just this year, our men's and women's cross country team took the national championships, the best college runners in the nation, pretty impressive. One of the things they do is they take these ketone drinks before they train and before their rate, they race some more and more of the tour de France teams. Tour de France teams take ketone supplements because it is just another fuel. It is something And they're like, oh, we're going to do this. that the body can burn, that we always say, well, once you start running out of glucose, you're going to bonk or you're going to hit the wall. Well, what if you don't really use glucose because you're burning a lot of fat and a lot of ketones instead, and that keeps your glucose kind of untouched or you're not relying on the glucose? And we see this in humans. If there's a human that has adapted to a ketogenic diet, they burn fat at a higher rate than was ever thought humanly possible, that that fat is basically fueling all of their muscle movement during the exercise session rather than relying predominantly on glucose the body has adapted it's burning fat for fuel and when available it's burning ketones for fuel and it's leaving the muscle as sort of a last resort when it really needs a big kick
Speaker 2i've seen these keto drinks yes little they're almost like little shots well
Speaker 1there's a bunch of different types if you look at the spectrum of ketones on one end you have the cheapest most readily available although less effective called ketone salts, where it takes a molecule of ketone and binds it to a mineral like calcium or magnesium. Not as effective. And it's a lot of minerals. So people will find that they may get a lot of plaque on their teeth, maybe increased risk of kidney stones. So it comes with some consequences. Then you have the ketone ester, which often comes in shots. Then you have the bioidentical BHB or the bioidentical ketone. One company, which is Original Ketone, they make it. Now, more effective, you take a little bit of these and you get an increase in ketones. They're a little more expensive too. But as the space is becoming more competitive, the price is coming down.
Speaker 2And what exactly does it do? So if I took a shot of identical ketone drink, what would go on in my body and how would that impact my cognitive performance or athletic performance?
Speaker 1Yeah, yeah. So it would result, so you're drinking it in, you're immediately absorbing it from your gut. So if you were not in ketosis, let's say you had, and I'm not encouraging people to do this, you would just have eaten two bagels and a cup of sugary coffee. You're no ketones, undetectable because insulin has come up. It's inhibited ketone production. And then you drink a shot of the ketone. Within an hour, we would detect your ketones. They would have gone up maybe to one millimolar, which is a pretty significant bump. Yeah. And they're capable of that kind of movement. And maybe you do so because you're thinking, I really need to be sharp right now. Would that make me sharper? Well, that's where we have to speculate. There's no, my lab published, animal evidence suggesting that yes, indeed, it makes you sharper. That we had these animals navigate mazes and recognize objects. And when the animals were on a ketogenic diet, they were much sharper. They were much quickly, much better at solving problems and remembering solutions to previous problems.
Speaker 2It's one of the, I asked this in particular, because as my team know, because I've said it to them a lot over the last couple of weeks, I've been on the keto diet and I've been literally pricking my finger to check my keto levels. And the highest, I've gotten to is like 2.5.
Speaker 1Which is high.
Speaker 2Is it high?
Speaker 1That's not problematic. Right. I mean, that is just proof positive that you're on ketosis, which itself is proof positive that you're burning a lot of fat. Yeah. And three, that your insulin levels are low.
Speaker 2Fat dropped off my body like I've never seen in my life. Exactly. Yeah, it's crazy.
Speaker 1So the power there is, like, if you'll allow me to kind of springboard off of that comment, the power of, so if someone is listening to this and they're thinking, okay, I need to shrink my fat cells. Yeah. Unfortunately, they don't realize that there's two variables to what caused their fat cells to grow in the first place. They have no awareness of the value of insulin in this, in this formula. All they do is pay attention to the calories. And so the average individual is looking down the road of this fat cell shrinking journey. And they're thinking, okay, what I have to do is just cut my calories. And what do they do to cut their calories? They do the exact wrong thing. And before I even answer that, let me just present the scenario. Let's imagine that Stephen and I, everyone listening is invited. Stephen and I are hosting a buffet. We have the world's best chefs. It is going to be a table filled with the most delicious foods you can imagine. You're in our invitation. We say, come hungry, because you're going to want to try a little bit of everything. Everyone listening, ask yourselves, what would you do to come as hungry as possible? You'd probably do two things. Or think, how did you go to your Thanksgiving or your Christmas dinner as hungry as possible? You would eat a little less in some period of time. You would go for the event, and you would exercise a little more, and it would work. You would be very hungry. That's why the traditional advice given for weight loss doesn't work. Because we tell people, eat less, exercise more. Sure, you maybe lose a little bit of weight in the short term, but all that does, you've given them the perfect recipe to promote hunger, and hunger always wins. As a good example, in the US, we have a game show. Maybe there was some version of this in the UK called The Biggest Loser. It was essentially, who can lose the most weight? And it was through a punishing regimen of caloric restriction. Eat less, exercise more. That is like the perfect embodiment of that approach. They were starving, and they were exercising to insane degrees. And oh my goodness, did they lose a lot of weight. And yet, you never see them again. They don't do a reunion tour five years or ten years later, because they gain it all back. Do you know they gain it all back? They do. In fact, a paper published in the US from the National Institutes of Health documented not only the degree to which they gain weight, but also how it almost literally breaks their metabolism, that normally a person's metabolic rate is connected to their body mass. A bigger body has a higher metabolic rate. A smaller body has a lower metabolic rate. This is just human physiology. And no surprise, when someone loses weight, there's less of body, and so metabolic rate goes down. As they gain weight back, metabolic rate will typically go back up as well. Except for the contestants in The Biggest Loser. They started with a high metabolic rate, and because of a high body fat level, they lost a substantial amount of weight. No surprise, metabolic rate went down substantially. But this is such a dramatic change that as they started gaining weight back, metabolic rate did not come back with it. It stayed lower than it should have. Normally, it's connected, sort of one to one. Wherever body weight is going, metabolic rate is going, except in these people. That method of dramatic weight loss through such severe restriction which is based purely on the caloric theory of obesity leads to significant hunger. So, no surprise, if a person's attempting to shrink their fat cells or lose weight, if the first step is, "I'm going to cut my calories," and they don't address their high insulin, they're never going to lose weight in the long run. They're going to step right back to where they were. Because if they start cutting calories, but insulin is still high, that's going to make them very hungry because insulin wants to be storing energy. A professor from Harvard, named David Ludwig, found this. If you have people eating a lower-calorie meal that spikes their insulin, it makes them much hungrier than a lower-calorie meal that doesn't spike insulin. So, that's the key. Anyone listening, if you're thinking, "I need to be on a fat-cell-shrinking journey," let the first step of that journey be, "I'm going to lower my insulin." -Which means? -Which means I'm going to control my carbohydrates. I'm going to stop eating carbohydrates that come from bags and boxes with barcodes. And while I am restricting those carbohydrates, I'm going to focus more on protein and fat. So, control carbs, prioritize protein, and don't fear the fat that comes with those proteins. Fat and protein together is a miraculous combination of helping you feel full. And it is literally giving everything you need. There are such things as essential proteins. There are such things as essential fats. So, focus on those. And that will be the key to helping insulin come down. Then, as you have found, you haven't-- And when you're hungry, eat. If you're not hungry, don't eat. But what the person will find is they're lowering their insulin all while their metabolic rate is going up. They're learning how to burn their own fat for fuel. Because remember the metabolic hybrid, that metaphor, that if you want to lose fat, you need to burn fat. You're not going to lose fat if you're always burning glucose. It's fat that you need to burn. And as you start burning more fat, you realize that it's like the hump of a camel. That hump exists because it is a big source of fat for that animal to be using its own fat for energy. We have our own version of that. So, where you think about the average individual who's chubby, they have hundreds of thousands of calories waiting to be burned in those fat cells. It's just that their chronically elevated insulin is never letting them burn it. And so, as the person starts making these changes in their diet to lower insulin, they now can finally start relying on their own fat for fuel, so it's no surprise that their hunger starts to come down. Let that be the natural way in which you're controlling your calories. Don't control your calories because you're forcing yourself to be hungry and eat less. Control your calories because you simply aren't hungry.
Speaker 2So, I'll overlay this with my own sort of anecdotal experience. So, I, every year, do a keto diet, usually for about eight weeks. This time, it's going to go on for a little bit longer. The reason in part why it's going to go on a little bit longer is I've just learned more about what's going on in my body. And also, because I podcast now and do a lot of speaking on stage and those kinds of things, I see tremendous variance in my ability for my brain to articulate what I want to say. I feel the same way. It's like, it's absurd. Yes. I was saying this the other night to the team that was with me here in Los Angeles, and I've tried to say it to so many people. As someone that can spend nine hours a day trying to think of the next question to ask or trying to remember the research or on stage in front of a thousand people, and trying to deliver a story or a point, I get to see variance, which I've never been able to explain, where some days, I'll go up on stage or I'll be in a podcast, and it's like my brain and my mouth aren't connected. And then on other days, specifically when I started doing ketosis or having a ketogenic diet, it just flows. It just flows so well. And I was saying to my team, it feels like I'm looking at the world like this these days. Like I've got this intense, for anyone that can't see me, I just stretched my eyes. Like I've got this intense focus on the world. And the other thing I've noticed with my diet is I get hungry, but not like I used to get hungry. And then very quickly after I start eating, I stop. I don't seem to be like doing like these, I used to kind of binge a little bit. I used to have like longer eating sessions and my hunger goes very quickly. I also found that I didn't have these like fluctuating energy levels throughout the day. I don't crash anymore. I used to get like slumped. I don't slump anymore. And then the other thing which a lot of people care mostly about is the fat, so like belly fat. I have never seen anything that has stripped belly fat off me faster. And I'm talking in a matter of weeks that I could count on one hand than doing the ketogenic diet. And if I could literally show a picture of my scales, because I have these digital scales on the screen, and it's just trundling along, and then there's this cliff edge where it goes directly down and so much so actually that one of my concerns with the ketogenic diet is how the hell do I keep my muscles muscle
Speaker 1oh that's a great question
Speaker 2because my girlfriend to her credit when i did ketosis the first time she was like i've never ever seen you look like this when i took my top off but also it was quite clear that my my muscles had got smaller i was lean as fuck but my muscles were smaller yeah yeah so with with caution this time i did ketosis again and i've been thinking how the
Speaker 1fuck do i keep my muscles yeah yeah okay so first of all let me just add a hearty amen i'm an advocate of a ketogenic diet although it can be applied differently across different people but i would say anyone would benefit from having some modest period of time of elevated ketones at least in some portion of the day now how do you maintain muscle mass in the midst of such obvious weight loss i can only speculate now there are peer-reviewed studies that i can cite which do support the idea that a human can be on a ketogenic diet and have a total maintenance of muscle and strength that is public so we know it's possible although that isn't that doesn't seem to be what happened with you i would suspect that there were two things two things happening possibly now i'm speculating here and i'm pretending to be your coach or your expert here one could have been that you had relatively lower energy during your workouts because of a slight degree of dehydration and then the other one would be calories which i'll come back to in a moment i just wanted to put it out there so when insulin comes down one of the other one of the many effects in the body is that another hormone comes down called aldosterone which is one we've never invoked yet but low insulin leads to lower aldosterone when aldosterone comes down the kidneys become much uh begin to eliminate salt and water much more rapidly now that's not problematic but it does mean that a person does have to focus more on hydration and salts so if someone's going on this strategy and they actually have to focus more on exercise fairly often you need to be much more focused on your hydration literally drinking more because you will be urinating more which is partly why people's blood pressure gets so good so quickly and just to pause on that point there if someone is on one or two blood pressure medications and they adopt a ketogenic diet they usually have to stop their medications within two days because their blood pressure goes to normal so quickly that if they stay on the medication they're going too low so one of the things that i've seen is that people who are on a ketogenic diet one could be that you were actually working out a little less intensely because of the dehydration but then two it's possible that you were eating too few calories to actually maintain muscle muscle is a hungry organ it is metabolically expensive for the body to keep that muscle on and as you start to get leaner and leaner it gets harder and harder for the body to defend that muscle in fact that's the difference between fasting and starvation the longest known evidence of a fast was a man in the uk who fasted for 384 days literally not eating or drinking a single calorie he was under medical supervision getting vitamins and minerals and water and he was went to live on went on to live a perfectly healthy life um so but what was the difference why was that not starvation starvation is when you run out of fat so you might have gotten to the point of so lean that you didn't have enough fat to burn to make enough ketones to fuel the brain if you don't have enough fat to burn to make enough ketones and the brain is saying all right well i wanted to switch to ketones so that i could spare the glucose but i can't there's not enough ketones here so i have to rely 100 on glucose but if you're not eating glucose now the body has to start stripping the protein from muscle and it sends those amino acids to the liver then the liver is so capable it will turn those amino acids into glucose so it turns my muscle into glucose to feed the brain so my comment then getting finally getting to my answer is in your version of a ketogenic diet with your level of muscle mass and your inherent metabolic rate based on your body size and your activity you probably ought to eat more fat i wasn't
Speaker 2actually doing the blood tests at that point i'm doing it this time around yeah but i wasn't doing the blood test so i can actually see my keto levels yeah so maybe i wasn't even in ketosis because i wasn't you might have been
Speaker 1but it could have been that you were simply not eating enough calories i have to so this is an example where that's what i'm trying to do this time i'm trying to eat more fat like every time you're making a steak put butter on there and when you're drinking a cup of coffee as crazy as it sounds i drink yerba mate every morning i will put a big dab of butter like a big dab of butter in my tea and i'm sipping on it while the world's still asleep and the kids are haven't woken up yet and so i know because i want to keep my muscle as a guy who's almost 50 um i i find that when during my strict ketogenic phase and i'm currently in it as well every january i go to kind of a carnivore diet and i mostly do it to one lean down but also to check any addictions and habits i don't like feeling addicted to things and and my wife will comment and even as an almost 50 year old it's fun to see my six-pack coming i don't want to lose my mass my muscle mass because you have to work so hard to get it yeah and what i find is if i increase my fat i always get plenty of protein but if i increase my fat content i have an easier time maintaining my bulk are there any
Speaker 2downsides of following a ketogenic diet that we need to be aware of
Speaker 1the only downside i can articulate so in fact i didn't even finish because i distracted myself mentioning some of the benefits of ketones but ketones are further anti-inflammatory like they directly reduce inflammation in the body by inhibiting inflammatory processes and they also improve antioxidant defenses so it helps reduce oxidative stress so ketones do have benefits that go beyond even what we've taken the time to articulate if there's any negative to a ketogenic diet it could be that you start you acutely or you temporarily become less metabolically flexible now that's me invoking a term we haven't brought up yet but metabolic flexibility is is a term to refer to the body's ability to when it eats glucose to burn glucose when it's not eating glucose it burns fat so you're shifting between the two metabolic fuels that we outlined earlier when someone has been adhering to a ketogenic diet they're not adhering to a ketogenic diet for some time it's almost as if their body is stuck in fat burning mode and that if you and i being in such adapted ketogenic state as we are if we were to go to lunch and eat two bagels and a sugary drink it would take us a very long time to clear that glucose from our blood much longer than otherwise like let's say we go out with the production team they're eating a normal higher carb diet all things equal same body size same activity their glucose levels would come up and down in 90 minutes for example perhaps yours and mine may take 180 minutes to come back down so the person may say well gosh steven and ben are no longer burning glucose very well and that's true in that one moment um our bodies had almost forgotten what it was like to burn a bunch of glucose because we had adapted to fat
Speaker 2burning so what about the gut microbiome oh yeah because i told someone who is a nutritionist that i was doing a keto diet at the and they said oh your poor gut
Speaker 1ah yes well what a naive um thing to say if i may gently reprimand your friend there's no evidence to support that there's any harmful change in the microbiome in fact a paper was just published that looked at a man who went from a normal omnivorous human diet with abundant plant matter to a purely carnivorous diet literally zero carb and they documented precisely no change in his microbiome none whatsoever but it's is he eating plants no well he had been eating plants so the case study was a person eating a normal diet of plants and meat a normal omnivore diet and adopt and then looked at the microbiome and then adapted to a purely carnivorous diet purely meat and the microbiome didn't change at all what's the time period months i think the problem with the microbiome the reason i don't take microbiome research too seriously as a scientist is that it is a big black box you you came from the uk to london to to la to california if we took a microbiome sample analysis of your time in the uk now it would be different now even though you're eating the same but you're drinking different water you're breathing different air things i was just on a plane from utah to california give me a day or so i would have some sort of shift in my microbiome so the microbiome can change in response to all kinds of things the idea that you somehow have decimated your microbiome because you aren't eating fiber is absolutely false that is that is completely false now there might be a change in some of the population of your microbiome more of one less of another but there's no evidence to suggest that's problematic your microbiome is intact those bacteria do not die they're just simply metabolizing other things maybe they're relying more on short chain fatty acids maybe they're relying more on amino acids they're not eating as much they're not eating fiber but there's still stuff in the meat or the eggs that the microbiome will eat
Speaker 2but if if if eating lots of plants does give me a more diverse gut microbiome then if i stop eating plants i'm gonna have a less diverse gut microbiome yeah
Speaker 1but but steven but even then there's a bit of an assumption built into the question because it's do we know that the microbiome will be less diverse the case study i just mentioned found that in this one single man it didn't change his microbiome at all it was the exact same populations in all the same
Speaker 2Because aren't the plants like feeding the bacteria?
Speaker 1bacteria yeah yeah so the the fiber is so fiber will but again it's not that's not the only thing bacteria can eat bacteria can eat fats bacteria can eat amino acids they can eat glutamine for example they um they can even meat will have a little bit of glucose in it where the muscle has something called glycogen and so there's you know trace amounts of glucose and even the meat that you're eating so i do not look at the argument that you know you're destroying your microbiome that has no that has no scientific support you may be changing your microbiome but who's to say that's a bad change maybe it's a better change you certainly are feeling better you're thinking better you're getting leaner your insulin sensitivity is improved cognition is improved i would argue if there is a change in your microbiome it's probably one that's for the best and no one can prove that wrong as much as i just stated that comment in a speculative fashion it's speculative because there's no evidence this is why i look at the microbiome and just say yeah it appears to matter but in ways that we
Speaker 2don't know but the the you agree with the argument that if i sat here now and i ate a wide range of plants for the next let's say six months when you analyzed my gut microbiome it would be much more diverse i'm
Speaker 1not agreeing to that
Speaker 2really i
Speaker 1don't know if that's true um and again i would cite that one case report i just mentioned now which is the a man who did this they reported that the microbiome was identical that there was no significant change that
Speaker 2that's just one man
Speaker 1it was one man it was a case report which is not a randomized clinical study so um but even still i i with my speculation um heavily handed here i would say probably more diverse microbiome but i would say but then the next step is a harder one which is is that good or bad i don't know maybe all you're doing is promoting the growth of bacteria that make more gas because they're fermenting the fiber and you just have more flatulence as a result of it people dieticians will say well a diverse microbiome is a good microbiome we'll prove it how do we know that how can you prove that to me as a basic scientist i want to see the hard evidence because what i can prove is that we can take humans who are overweight and diabetic and hypertensive eating a standard american or global diet and put them into a ketogenic diet which is going to be a much simpler diet and yet every clinical marker gets better and so if someone were to say yeah but sure you've reversed your diabetes and your hypertension but your poor microbiome i would say well i don't care about my microbiome i care about the human and so if there's less diversity but every single clinical marker has gotten better perhaps more diversity is not what we want in our bacteria and i'm speculating but so is the person who
Speaker 2states that yes i i'm not aware of um research that links the two um but i i could always have a look but um i would i was always under the assumption that a more diverse microbiome is a healthier person yeah and i don't know
Speaker 1yeah but but do you do you feel
Speaker 2healthier now um feel healthier i certainly feel and it's only been a short amount of time so i don't know what what my health might look like if i'd done this for like two years right because then there could be a really sort of deeper change to um i know people who've done it for
Speaker 1more than two years and they're
Speaker 2they're great because some of the some of the changes that occur in our health take time now you you show this a lot in your work with insulin resistance that if you're insulin resistance for 10 years your brain i think i read in your work is like it ages it ages by an additional two years yeah yeah it
Speaker 1accelerates the aging and i
Speaker 2wonder the same thing with like my gut microbiome if i'm if my gut microbiome is not diverse so i have a very sort of um narrow diet or you know i'm not getting not eating my plants could it take me a couple of years to really understand the net negative impact that that has on my overall health
Speaker 1it's entirely possible yeah yeah i would just i would just ask that we be careful with the i would just ask that we be careful with the an increase in diversity with more plant matter that's an if um is that change beneficial it are the bacteria that we're now promoting the growth of are they better for us or are they just bacteria that exist in order to handle more fiber and again the outcome being that perhaps it's just making more gas um you know the more plants you eat the more gas you have to produce by fermenting more fiber what if those bacteria are only existing to just eat the fiber and not actually improve the human host at all
Speaker 2so ketosis possible to live in us it's i think one of the important points on ketosis is when i do my blood keto test i fluctuate wildly after i've gone for a run my ketone levels are super high sometimes later at night i'm just on the verge of ketosis sometimes um and i think that's interesting because we don't have to live in this necessarily deep state of ketosis the whole time we can fluctuate uh yeah a little bit yeah yeah maybe even sometimes
Speaker 1my thought on it is that a person would benefit from some state of ketosis on a frequent basis if for no other reason than to really give the brain a heavy dose of just straight energy um not that everyone needs to be as strict as perhaps you and i are being at the moment um but i would say the more a person has a disorder or a disease that benefits from ketosis the more than they ought to focus on it like if someone has type 2 diabetes if they adopt a all of their diabetes medications in months all of them um if someone has epilepsy if they're or migraine headaches if some of the from 1913 i think was the first published report on this if there's someone who suffers from migraines as long as they're in ketosis they may never have another migraine again i mean it is completely curative or preventative for the same with epilepsy that many forms of epilepsy so depending on the person they would benefit from being in for everyone else who's just sort of a normal individual who wants to be lean and keep their brain healthy and happy etc i would say it's generally prudent to just control your carbs be mindful of the type of carbohydrate you're eating and as i said earlier just try to focus on the carbs that don't come from bags and boxes with barcodes i'm actually quite liberal in my view when it comes to whole fruits and vegetables i'd say eat them enjoy them liberally but then also make sure you're getting some good protein and fat because there's no such thing as an essential carbohydrate that sounds controversial but humans do not need we have no requirement for carbohydrate we do have requirement for fat and
Speaker 2protein what about artificial sweetness yeah one of the things that i am tempted by when i'm on a ketosis diet is like the soda zeros of the world or the diet sodas of the world what impact does that have on my insulin
Speaker 1levels yeah yeah great question there is such a breadth of of diversity when it comes to sweeteners from artificial to natural to another rare sugar more and more you know there's all these random i'm not random but a very broad spectrum of molecules that we have developed or found that taste like sugar but don't have the effect of sugar so on on the good end are things like that have been shown to have no insulin effect and so you know i appreciate everyone listening letting me kind of stay with that as my framework people are going to go on and criticize all kinds of other things about other sweeteners and that's just too broad that's a topic for a whole book with regards to just insulin on the good end where they have no effect it would be one as common as aspartame so like diet drinks not the zero drinks but the diet drinks will have aspartame as the sweetener is it a difference there is a difference and i'll get to that other one in a moment so i should be having diet instead of zero well i personally go to diet rather than zero um but that's because aspartame is the sole sweetener in the zero in the diet rather and it has no effect on insulin so to erythritol uh sorry erythritol is a little right around aspartame is generally a good one but monk fruit extract stevia and especially allulose those are inert when it comes to insulin you know allulose stevia monk fruit extract um aspartame no effect erythritol no effect but erythritol that ending ol is reflective of a class of sweetener called the sugar alcohol and that does not mean it's alcoholic that just refers to the actual chemical structure that puts it in the alcohol family once you get into the sugar alcohols you start to get a little problematic where erythritol is a good one and xylitol is generally a good one but then you get to things like maltitol and mannitol and they do have an insulin effect and what was what
Speaker 2kind of foods have
Speaker 1those yeah so often like you can get in like artificially sweetened chocolate sometimes for reasons that i don't know i don't know why the food formulator puts them in some things and not other things the the problem i chuckle because it becomes so apparent with some of those artificial sweeteners like the sugar alcohols is that as you eat them you taste it sweet in your mouth and it doesn't have any caloric value in the body because it stays in the intestines and this is something that is largely unique to the sugar alcohols whereas that stays in the intestines and it stays in the intestines and it stays in the intestines it starts pulling in water from the body which starts to create a fairly inconvenient degree of flatulence and diarrhea and so a person will know if they've eaten too many of those types of sweeteners because their intestines will tell them so so but also on that spectrum kind of in the middle is the one that's in the zero drinks which is one called sucralose and while sucralose is generally not a problem with insulin it is a sweetener that has been shown to cross the blood-brain barrier and so the reason i avoid the zero drinks and refer or go to the diet drinks is that aspartame does no such thing aspartame just gets divided into amino acids we just digest it and absorb amino acids sucralose will go can cross the blood-brain barrier and i don't know what it's doing there but i don't want it there and so i avoid the zero drinks because i don't want that sweetener but but personally when i'm adhering to this diet a diet soda is my actual indulgence where i want something sweet and yet i don't want the metabolic effect of it one thing you
Speaker 2mentioned earlier which i've been thinking a lot about is salt and i think a lot about salt because i went to the doctor many years ago and i think i was using this like maggie seasoning that i put on my food and the doctor said to me that my salt levels were too high and i and then i've heard since then from other people that we're actually probably not getting enough salt in our diet yeah
Speaker 1so i'm interested to hear that your physician would have said your salt is too high that is very rare that that gets measured it's not sodium i think yeah yep they could have measured sodium and that could have been higher they absolutely could have it's just not common so salt has been has earned a terrible reputation because of a series of studies that implicated salt consumption as a cause of high blood pressure and and really briefly as a as a momentary physiology professor that is a real effect and i think that's a really good point because i think that's a really good point and i think that's a really good point because i think that's a really good point because i think that's a really good point if you and i were to go eat salt our body for the next several hours afterwards would retain its water in order to balance out the salt so that we didn't get too salty so we would retain water in order to keep our salt at a normal level and so that could be reflected by an elevated blood pressure however multiple huge studies have found that if you go to a population of humans that have high blood pressure and you tell them you need to cut your salt in order to correct your blood pressure they may at most move their blood pressure by one or two points it has an absolutely negligible irrelevant effect and it's because salt is not a key contributor to blood pressure it's actually insulin resistance insulin resistance will force the body to hold on to salt insulin resistance will force the blood vessels to be very constricted all of which play together to make for a very high blood pressure so as much as we have been telling the world that we should be cutting salt we should be cutting back salt no we should have been telling them to cut back on what spikes your insulin refined starches and sugars but with regards to salt it's interesting for me to note where did that whole view come from within the united states decades ago there was a study that was published and they called it the dash diet dietary approaches to stop hypertension d-a-s-h the dash diet and in the dash diet one of the critical changes was to tell people to eat less salt and when they found that when people adopt a dash diet it's amazing their blood pressure goes down however unfortunately they also tell people to do lots of other things with the dash diet like when they tell someone to go on the dash diet they also tell them to eat less sugar and less refined starches and sugars well it's possible indeed i would say it's absolutely the case that what's actually lowering their blood pressure isn't that they cut their salt back it's that they were cutting their refined starches and sugars back and it's that that had the main effect and the cutting the salt was just some innocent bystander but to put a fine point on it in human studies if you have humans cut back their salt considerably they become insulin resistant so take a healthy group of humans say you need to eat less salt and they do so if you measure them a week later while they're adhering to this they will be significantly more insulin resistant than before they ever cut back their salt it's one of the ironies of the whole scenario where a physician may be telling a patient with high blood pressure you need to cut back your salt and they end up eating less salt and yet their their blood their blood pressure gets worse it's because the main contributor to high blood pressure is insulin resistance and by telling them to cut back on their salt you made them more insulin resistant and that whole mechanism is because one of insulin's many many effects is to want the body to hold on to salt and water and so if you start cutting your salt all of a sudden insulin says well there's little salt coming in i need to do what i can to retain whatever salt we do have and so it starts retaining salt and water more in order to try to offset the lack of salt coming in and while insulin's going higher and higher the body's becoming more and more insulin resistant so salt restriction can cause insulin resistance in humans you
Speaker 2talk about four pillars to eating in your book while we get sick you outline these four essential pillars to develop a strategy for maintaining low insulin levels and combating insulin resistance what are the four pillars yes
Speaker 1so when it comes to controlling insulin resistance the key is to manage macronutrients and the best way to manage macronutrients is going to be a strategy that helps lower insulin lowering insulin is the key to both slow insulin resistance and fast insulin resistance so the more insulin the more effective it's going to be and there are poor there are four pillars so the first one control carbohydrates second prioritize protein third don't fear fat and then fourth after the first three have been taken care of four frequently fast so with the first one very briefly by control carbohydrates i mean that it is time to focus more on whole fruits and vegetables eat them don't drink them and then don't get your carbohydrates from bags and boxes with barcodes that the more you're opening up a package and getting your chips or your crackers or your cereal or your bread the more you're going to be spiking your glucose and your insulin keep that on the shelves at the grocery store focus on whole fruits and vegetables that's going to be the key for number one control carbs now while you're eating fewer carbohydrates you need to eat something and so prioritize protein i would say particularly animal source protein which is the best source of all of the amino acids that humans need and then with those proteins will come fat don't fear that fat that's number three fat is very satiating when combined with protein when fat and protein come together we digest it better sometimes people will find that if they just have a scoop of whey protein it can be very upsetting on their stomach it's because we're not to eat protein alone in nature that never happens in nature protein always comes with fat that's how we should eat protein and that's how we should eat protein and that's how we should eat protein we should eat it we digest it better and human studies have shown that when a human eats pure protein there's some degree of muscle growth albeit microscopically minuscule but when we eat protein with fat we have significantly greater muscle growth than we do with the protein alone so that is the three pillars that encompass the macronutrients or the big parts of our diet but once a person has done that then they are well positioned to adopt a strategy a structured strategy of fasting and that can be there are as many ways to fast as there are people who want to do it there's no right way or wrong way my goal by invoking that fourth principle and and i do think it should come last once you've learned how to eat better food your your body has adapted to burning its own fat for fuel but it can take the it can take uh intermittent fasting where it's one meal of the day you're fasting through um it can do where people do alternate day fasting there are different ways to do it even if i'm in ketosis then you don't need to do it as much because you're already lowering your insulin so if a person's already in ketosis in fact if a person were in ketosis and frequently fasting um depending on how lean they are it's going to become extremely difficult to retain muscle yeah so those are the four pillars it will be an extraordinarily effective way to address insulin resistance but the problem as i started when i that i mentioned is that while these concepts are simple that does not mean they're easy because humans show addiction addictive tendencies to only one macronutrient not fats not proteins all of the evidence of the neurobiology of addiction in humans points to carbohydrates and so as much as i lay out this simple plan it can be difficult and this is why this self-discipline required is difficult enough that it's why people find that they have to result in you know relying on drugs for these kinds of things
Speaker 2physical activity exercise useful for keeping my insulin levels in check
Speaker 1yeah yeah i'm really glad you brought up exercise i'm an enormous advocate of exercise the best exercise to improve insulin sensitivity is the one you'll do and so if someone listening to this is an 80 year old grandma and um if she if her form of exercise is walking around the street down around the block with her girlfriends but then if someone else has the ability to go cross-country skiing or crossfit do it so the best exercise is the one you'll do now having said that the better exercise is the one that you're going to you'll do that keeps muscle. Muscle building work is going to be minute for minute, a more effective way of improving insulin sensitivity than, than any kind of aerobic activity. And that's because muscle is the great consumer of glucose. And back to the, in fact, not only does muscle eat the most glucose from the blood, but it's also how it eats the glucose when it's exercising. So earlier we talked about how insulin kind of comes and knocks on the door of the muscle cell and then the muscle cell will open the door and allow the glucose to come in, thereby lowering blood glucose, unless the muscle is exercising. When a muscle is exercising, and I'm kind of mimicking the contraction and relaxation, relaxation of a muscle, when the muscle is exercising, it has its own way of opening those doors. So there's an insulin independent method where the muscle cell essentially tells insulin, insulin, I know normally I have to wait for you to come and open these doors, but I'm so hungry during this exercise that I'm not going to wait. And so the door is just open. So the contracting muscle has its own way to rush, to pull the glucose in, which means of course, that a person is going to have an easier time controlling their blood glucose, which in turn would mean a better time controlling insulin. But the more muscle a person has, the easier it is. And this could be one of the reasons why, if you look at longevity and look at the markers of muscle strength versus the markers of cardiovascular aerobic fitness, the aerobic fitness markers are terrible predictors of longevity. It's muscle and strength that predicts longevity for multiple reasons, including just the very act of living and moving, but also because if you have more muscle, you're going to control your glucose better, which means you're going to control your insulin better. Then you're back to these variables that people use to predict, or what are the most accurate indicators of longevity? It's who has the best glucose control. More muscle helps that happen.
Speaker 2There's a big debate around whether we should be calorie restricting and low fat diet, whether we should be calorie restricting and a moderate fat diet, or calorie restricting and a low carb diet. Yes. What's your take on that?
Speaker 1Yeah, I am unabashedly in favor of carbohydrate restriction. I would say for two reasons, that one reason I think that carbohydrates should be the macronutrient that is most scrutinized is because it's the one we eat the most of. Seventy percent of all calories consumed globally come from carbohydrates. That is the one that has the biggest insulin effect, and that's a problem for all the reasons we've discussed. But two, carbohydrates are not essential. This is controversial. People don't like to acknowledge it, but there is literally no biological need that humans have for carbohydrate. In the United States, a report decades ago from the Department of Agriculture, looking at the needs of human nutrition, there's a quote there, and I'm not going to get it exactly right, but I'll get it pretty close. It stated in this document that the lower limit of carbohydrate consumption in humans is zero. In other words, there is no such thing as an essential carbohydrate. Now, I'm not saying, well, then let's not eat any of them. No. But I am saying, why is that the one we focus the most on? As 70% of all calories globally are coming from that one. You're telling me that most of what we eat comes from what we don't need? Why not put the focus on the things we do need? There are such things as essential fatty acids. Let's eat fat. There are such things as essential amino acids. So let's eat protein and make sure we get what we need. And then on any remainder of the plate, we can get some other things that we want to nibble on, like plants.
Speaker 2Why don't we just tackle this off and just take a break?
Speaker 1Ah, yeah. Great question. So I have kept my finger on the pulse of the whole field of gut-derived hormones, which is what we talk about with these weight loss drugs, almost since their beginning. My dissertation work was in a lab, one of the first funded labs to look at these drugs, although in the context of diabetes. And then it's blossomed into the context in the use of obesity. This is the class of drug, GLP-1 receptor agonist. First of all, what is GLP-1? GLP-1 is a hormone that we all make from our guts. Our small intestine will make GLP-1. We're making it all the time to varying degrees. Some things we eat will result in a higher GLP-1. Sometimes it'll be a lower GLP-1. Like, for example, a paper just published a few months ago found that if you have people eat the exact same meal of calories, but lower carb or higher carb, the lower carb version of the meal will increase GLP-1 three times higher in the blood than the high carb version of the meal. So if you have people who eat the exact same meal of calories, the lower carb version of the meal.
Speaker 2Which means that they'll feel.
Speaker 1Yeah. So what's the point? Who cares about GLP-1? One of GLP-1's main effects is to tell the brain that we're full.
Speaker 2Okay. So more GLP-1, less hunger.
Speaker 1More satiety. Yeah. More GLP-1, less hunger, which is very impactful. In fact, I would be remiss if I didn't mention a study that was published in Humans a while ago. They took obese humans and lean humans and had them eat fat, pure fat. And they found that the GLP-1 response was the same. Whether you were lean or obese, you had the same amount of GLP-1. That would suggest that whether you're lean or obese, both of your brains in both of these populations will have the fat and have the same sense of, I'm full. Because it was matched with GLP-1. However, when they had these same groups eat pure carbohydrate, the lean group had a robust GLP-1 response. Big GLP-1. In other words, they would eat the carbohydrate and say, I'm full. Because GLP-1 would tell them so. However, in the obese group, they ate that exact same amount of carbohydrate and they had an almost negligible GLP-1 effect.
Speaker 2They were still hungry.
Speaker 1In other words, they would eat the same amount of carbohydrate as their lean counterpart and then just say, okay, what's next? I'm still hungry. And so it is prudent to focus on GLP-1. GLP-1 is a powerful hormone that does have an effect on human health. What I feel inclined to comment on is the negative side effects. Because the only thing we hear about is social media influencers extolling the benefits. And hey, I'm on this weight loss drug and I've lost 50 pounds. Someone has to be the voice that says, yeah, but what about this? And there are some significant but what abouts when it comes to these weight loss drugs. One of them is the loss of muscle mass or lean mass. You've mentioned a couple of papers from the New England Journal of Medicine, a paper a couple of years ago from what was called the Step 5 trial, looking at these drugs. They found that for every six pounds of fat a person was losing on these drugs, they were losing four pounds of fat-free mass or lean mass. So 40% of the weight they were losing on these drugs is coming from lean mass, like including muscle and bone. So there are now case reports of young healthy women who are overweight who go on the drug for some period of time and after they get diagnosed with osteoporosis. Where they have eroded their bone health, they're losing lean mass. So again. They've eroded their bone health. Yeah. So 40% of the weight that people are losing on these drugs appears at these high doses is coming from lean mass. So fat-free mass, including muscle and bone. The reason I find that so troubling is that in the UK, at two years on the drug, 69% of people get off the drug. They don't want to be on it anymore. And now imagine this in individual. Imagine, if you will, a 60-year-old woman who's been on the drug. I take that age and that sex on purpose because it's so hard for her to grow new muscle and bone. Let's say she's been on this drug for a year and she's lost 20 kilos. Well, 40% of that will have come from her lean mass and 60% of it came from her fat. And then when she gets off the drug, now all of a sudden her lean mass, her muscle and bone, that's never coming back. The muscle and bone that she has lost is gone forever probably at that age because after the age of 60, good luck developing new muscle and bone. But what can come back rapidly is the fat mass. And so at two years, she decides to get off the drug, which again, about 70% of people do. They're going to gain that fat back, but they're not going to gain their muscle and bone back. That is a significant loss that may be, depending on their age, gone forever.
Speaker 2I was scrolling on Twitter the other day and I saw a video going viral, which is now being reported in a bunch of news publications. It was yesterday that I saw this video going viral. And I'm going to play this video to you. It's from a singer called Avery. And she talks about her experience with Ozempic. I just
Speaker 3left the doctor's office. I went to get a checkup because I'd been off of Ozempic for two months now. And I just wanted to see if my body was in better condition. If there were any permanent damages. Kind of in shock right now because I wasn't expecting this, but I guess Ozempic can cause bone density loss. And I didn't think that that would happen to me because I was only on it for a year. But I have significant bone loss. I have osteoporosis and osteopenia. So there's like several of them that I have. And I wasn't expecting that. But that's what happens if you. you use ozempic for weight loss and you lose too much weight.
Speaker 1Yeah, I wonder. She's so lean. I wouldn't be surprised if she had it even worse than normal because we see it has become, I don't mean to suggest this is the case for her, but you do see people using these weight loss drugs who are already very lean. I mean, I've got a picture of her
Speaker 2here and she does look incredibly lean
Speaker 1already. But see, this is what people are doing. They're basically using it to facilitate an eating disorder in the people who are lean. This has become so common that there are complaints saying that, you know, lean, healthy people are getting the prescription and people who are obese and diabetic aren't because of shortages. The more the leaner, I've seen this. I know someone personally who is already a perfectly lean, healthy woman. And then she now looks sickly. And what caused it? Well, she wasn't lean enough. And when you take enough of that drug that you have no more hunger because of how it's acting at your brain, you do just stop eating. And the malnutrition, at least in part, is going to cause a loss of lean mass. But that also is even further exacerbated by the mental health problems where there was a paper recently published with the use of these drugs, finding that people, when they begin the drug, their risk of suicidal thoughts doubles. It goes up by over 100 percent. And their risk of major depression triples. And this so as much as we talk about these drugs and we say the drug helps you control your cravings. What it's what it's doing is perhaps reducing your craving for everything that while you're eating less food, which is resulting in the weight loss, you also are not interested as much in exercise as you used to be, which is going to make it even easier for you to lose your muscle and bone. You're also less interested in hobbies like going to play a ball with your friends or going out and drinking with the boys. So there is this kind of what's reflected across all of their interests is that their cravings for everything starts to decline.
Speaker 2On the case of that girl mentioned there, Avery, I've just seen she's uploaded a post that says, thanks. My record label told me I was fat. They dropped me. I got addicted to a Zenpec. Oh, my gosh. And now as a result, I have osteoporosis and my bones are as fragile as wafer cookies.
Speaker 1Yeah, it's hard. It's heartbreaking. So now that.
Speaker 2Obviously, you know, these are claims that she's alleging. Now we don't know the full picture of her health and there might be something more.
Speaker 1Yeah. But we do know, based on that one report, that 40% of weight loss is coming from fat-free mass. And so it is in people's best interest to be mindful of that tendency and that if they're going to explore the use of the drug to do so responsibly. And I want to mention that kind of caveat or angle to everything, because I don't want someone listening to me thinking, all right, Ben says I should never touch this and it is uniformly evil and bad. I'm not saying that. I find that I have to speak a little more boldly about the negative consequences because nobody talks about them. What would she have done if she knew about them, for example? No one knows about these kinds of negatives because people want to sweep them under the rug. Now, I believe there is a use case for these drugs, although different from how it's being used currently. In my mind, the best use of these drugs is to help someone learn how to control their carbohydrate addiction, because it will help you control your addiction. Sweet cravings goes down significantly within six months of the person taking the drug. So I think in addition to getting proper education, and if I may be so bold, I would say it's those pillars I mentioned earlier, control carbohydrates, prioritize protein, and don't fear fat. All the more reason, prioritize protein and fat to help preserve your muscle and bone. Muscle and bone are not made of carbohydrate. They're made of protein and fat. Eat protein and fat. Lift weights to keep any of that lean mass you can. Keep the integrity of your bones intact, but take advantage of the drug helping reduce your cravings for sweet things especially. I would say find the lowest effective dose you can where you are able, with a little bit of self-discipline, where you're not assigning all of the self-discipline to the syringe that you're going to inject into your tummy. There is value in doing something to deny yourself something you know you shouldn't be doing. There's life lessons to learn there. And so enough of the drug that makes it a little easier for you to overcome your carbohydrate addiction. At the same time, you're learning how to eat well. You're learning how to eat properly by managing your macronutrients and lifting weights. And then over time, ideally, I would say you find that you are able to reduce the dose of the drug and then eventually get off of it
Speaker 2entirely. You're saying that I did also search to see if there was a link between a Zempec and bone density and there was no clear link in the studies that have been done. I don't know whether there's been a lot of studies done. It says in the studies and reviews, some of glutide generally shows no harmful effect on bone mineral density, although rapid weight loss itself can sometimes affect bone health.
Speaker 1Yeah, so I actually think it's an artifact. That's a term that we would use as a scientist to say that it's an effect that's happening without being a main effect. So I don't believe the GLP-1 drug is attacking the bone. I think it's because the person has just stopped eating and stopped moving. Remember what I said earlier, people find that they're just less interested in doing stuff, like going to the gym, for example. And so that is probably combining where a little bit of malnutrition combined with a little less physical activity means you're accelerating some lean mass loss.
Speaker 2One of the things that this podcast has taught me is that liposuction is dangerous. Do you agree with that statement?
Speaker 1I do. From a metabolic perspective, I absolutely do. Liposuction is not dangerous to fit into the clothes you want to wear, but it's deeply problematic for metabolic health. And that's because, as a reminder, it's not the mass of fat we have that matters most when it comes to metabolic health. It's the size of our fat cells. So let's imagine an individual who has more fat than they want in some particular part of the body. The best way to help them is to have a fat cell. And the best way to help reduce that fat is to shrink your fat cells. So that's very important for people to realize. When you lose weight, you're not killing fat cells. You're not getting rid of them. You're shrinking them. And small fat cells are very healthy fat cells. They are literally anti-inflammatory. They're releasing hormones that fight inflammation in the body. And they're very insulin sensitive, which helps the body, by extension, be very insulin sensitive. So very healthy. Small fat cells are healthy fat cells. The problem with liposuction is, is that you are going in, and rather than shrinking the fat cells, you are sucking them out. Now, let's say, like a study that was done in the U.S. in women. They found that when women had liposuction from their buttocks and hips area, which is where most women gain their weight, which is because of sex hormones telling her body to store that weight there, they may look at that fat on their buttocks and hips and say, there's more than I want. I'm going to suck it out. So they do. But they don't change their habits. So they're still eating the same way they were before. Essentially, now they have fewer fat cells, but the body wants to store that same amount of fat based on how they're eating. In other words, there's enough insulin telling the body to store a certain amount of fat, and there's enough calories to fuel that fat storage. But the fat would be saying, hey, we don't have all these fat cells in the buttocks and hips like we used to. Let's go somewhere else. And so it's no surprise that over the ensuing years, after she's had liposuction, she's been able to store that fat in the buttocks and hips. And so she's been able to store that fat in the buttocks and hips. And so not only does she not experience any improvement in any health marker, nothing gets better with regards to her health. And that is, again, reflective of the fact that it's the size of the fat cell that matters. Maybe she has lost 10 kilos of fat. That might be a little much for liposuction, six kilos. And you would say, well, you have six kilos of less fat. Clearly, you're healthier. And yet they're not at all. Nothing has gotten better. And then if you follow them over the years, they cannot gain that fat back. And so they're not getting that fat back. And on their buttocks and hips, because it was literally sucked out. And adults have a hard time making new fat cells. So it's no surprise that they start storing more fat in an area that wasn't sucked out, namely their belly. And so a woman who's gone through liposuction, yes, she will have lost fat by liposuction at her buttocks and hips. But if she doesn't change her lifestyle habits, the body will take those six kilos and say, well, I need to store those now somewhere else. Because you're eating in a way that makes me want to store that much fat. And so her remaining fat cells that are intact, get bigger and store a bigger burden. And so over time, it's no surprise that health outcomes can start to get worse. By having fewer fat cells, she's increasing the burden that the remaining fat cells have to carry. Not only does that result in a change in where she's storing fat, namely storing more on her abdomen, but all the fat cells will get bigger. And thus, metabolic health can get worse.
Speaker 2We have a closing tradition on this podcast where the last guest leaves the last question for the next guest, not knowing who they're leaving it for. And the question that's been left for you, Ben, is who in your life gave you a chance or believed in you when no one else did?
Speaker 1What a fun question. Thank you. Probably my wife. Frankly, I just adore her. I think about, so when we were newlyweds, we got married quite young, if you'll allow me to be a little personal for a moment. We both really wanted a family. We knew that we wanted to be mom and dad. And she really wanted to be an at-home mom, just full-time mom, which I loved. I benefited. My mother, who died when I was quite young, she was a full-time mom. And most of my memories come from her being home when I would come home from lunch or I had a tummy ache and she would come pick me up. And I mean, I thank God for my mother, of course, but also for the time I had with her because I had so little. And we both really wanted Cheryl to be able to be full-time mom. Mom is just that special. That meant as a young, newly married husband, I was anticipating a future where I would be the sole provider for the family. And it was very daunting, very scary for me as a 23-year-old. That's how old I was when we got married. And I worried, how am I going to provide for my family? And I would look at the trust that my beautiful wife had in me, and I felt inadequate. And I have moments where I remember young Ben in his early 20s as a newlywed and how scared I was and how my wife's ongoing devotion put us in a position where I both make a wonderful amount of money to provide for the family and help secure our future. And then at the same time, I was afraid that I would be the sole provider for my family. I still have a schedule that lets me be really home, to go home early and help one of our daughters with her homeschooling, which I do, to always not go into work until I've made breakfast for the kids. And we've had some family time. So much of all of it is just the support of my wife because at any moment, if she would have said, no, I'm done. You got to go get a job right now. I would have. I love her and respect her enough and even rely on her insight that I would have done it. I just really believed that, okay, Ben, you're not dumb. I didn't marry you for your looks. I think you've got something. I'm going to trust you. And that trust was, it was both humbling and scary, but also very empowering. And it's given us a beautiful life.
Speaker 2Ben, thank you. My pleasure. It's been truly eye-opening and you've answered so many of the questions that I've had for so, so long, especially as it relates to ketosis and the broader link between insulin, infertility, pregnancy, PCOS, all of these kinds of things, which are topics of conversation. Amongst my friends and people that I love. Ben, thank you.
Speaker 1My pleasure. Thank you.
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