Benjamin Bikman: How insulin resistance silently grows fat

Bikman explains how eating carbohydrate often keeps insulin high: it tells fat cells to store, and the same loop quietly drives Alzheimer, PCOS, fatty liver.

Dr. Benjamin BikmanguestSteven Bartletthost

Feb 6, 20252h 43mWatch on YouTube ↗

EVERY SPOKEN WORD

150 min read · 30,002 words

0:00 – 2:19
Intro
1. BBDr. Benjamin Bikman
  When we're looking at smoking versus vaping, vaping is probably worse in terms of the damage to the airway and the insulin resistance that comes from it. But this gets worse because we know that insulin resistance is the core for most chronic diseases that are killing us, and there's a handful of other lifestyle habits that's contributing to it.
2. SBSteven Bartlett
  That's horrifying. So tell me everything.
3. BBDr. Benjamin Bikman
  Dr. Benjamin Bikman is a leading metabolic scientist-
4. SBSteven Bartlett
  ... whose research focuses on the hidden epidemic of insulin resistance and its devastating consequences.
5. BBDr. Benjamin Bikman
  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 US have some degree of insulin resistance, and people hear this and think America's just fat and metabolically sick, but we're not actually the worst country when it comes to this. And part of it is because of how different ethnicities store fat, and I'll come back to that. But there's two roads to insulin resistance. So there's the fast lane, and I could make you insulin resistant in 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 diets that are massively contributing to slow insulin resistance. Now, thankfully, this can be resolved through four pillars, which are very simple.
6. SBSteven Bartlett
  We'll get into that, but why don't we just sack all this off and just take Ozempic?
7. BBDr. Benjamin Bikman
  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-
8. SBSteven Bartlett
  Holy (beep) . (coin clanging) 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 wanna 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 (coin clanging) 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 gotta do is hit the subscribe button. So actually, this is the first time I'm gonna tell you not to subscribe (laughs) because it might end up costing me an awful... (laughs)
9. BBDr. Benjamin Bikman
  (coins clattering) Woo! Woo!
10. SBSteven Bartlett
  (chill music)
2:19 – 5:05
My Mission to Help with Chronic Diseases
1. SBSteven Bartlett
  Benjamin, what is the mission that you're on?
2. BBDr. Benjamin Bikman
  My mission is to help people appreciate that much of chronic disease, we look at them as these siloed, individual, distinct disorders with totally distinct origins, and yet much of them c- uh, share a common core. It's as if they're branches growing from the same tree, and the conventional clinical care will look at these branches and give someone a prescription for a medication which is only going to prune the branch back a little bit, never actually solving the problem. It can just grow right back. And so we can look at most of these chronic diseases that are killing us globally and g- and then say, "Okay, 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, uh, heart disease to type two diabetes to f- uh, liver failure or fatty liver disease. All of them share a common metabolic core. That's my mission.
3. SBSteven Bartlett
  And what is that common metabolic core?
4. BBDr. Benjamin Bikman
  Yeah, it's a little-known problem called insulin resistance. In fact, when I first started this topic, I stumbled on one paper that documented how when fat tissue is growing, it increases the risk of type two diabetes. That was this concept in the early 2000s that was really getting a lot of attention, diabesity, this kinda dual epidemic of wherever we see obesity, we see more type two diabetes. And this manuscript outlined something that was, to me, a revelation at the time. It was so fascinating, where when fat tissue is growing, it starts releasing proinflammatory proteins. That inflammation caused a problem called insulin resistance, and then that got me into this realm of ex- understanding that other tissues of the body, as they become insulin resistant, then you start to spread the chronic disease, w- a- and, and essentially coming to the conclusion that something like hypertension, high blood pressure, which is the most common cardiovascular problem and the main contributor to heart disease, well, insulin resistance is the main cause of hypertension. Um, they call Alzheimer's disease type three diabetes, or more accurately, um, insulin resistance of the brain. Even the most common forms of infertility, in men, it's erectile dysfunction. Well, that's because of insulin resistance of the blood vessels. In women, the most common form of infertility is polycystic ovary syndrome, or PCOS. That's because of the insulin resistance affecting her ovaries and the ability to produce the proper sex hormones.
5:05 – 13:53
What Is Insulin Resistance?
1. BBDr. Benjamin Bikman
2. SBSteven Bartlett
  I guess the really important question here is what is insulin resistance? And can you explain this to me like I'm a 10-year-old because-
3. BBDr. Benjamin Bikman
  Oh, yeah, for sure. Insulin resistance is it's kind of a... it's a disorder that has two parts. It's like a coin with two sides, that as much as we think of... we, we think of one side just because we hear the word insulin resistance, but there's another part to it that I need to... that is very important. So insulin, first of all, is a hormone that we make from the pancreas, a long kind of gland tucked underneath the stomach, and the pancreas is a very busy organ. It makes a lot of different hormones. It makes hormones that come into the blood. It also makes enzymes that go into the d- 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 one diabetes, their immune system has destroyed their beta cells, so they don't make insulin anymore. That's why for a person with type one 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.
4. SBSteven Bartlett
  So I eat sugar.
5. BBDr. Benjamin Bikman
  You eat sugar, or not even something as obvious as sugar, but bread or, or crackers.
6. SBSteven Bartlett
  White rice.
7. BBDr. Benjamin Bikman
  Chips. Oh, yes. Yes. So basically, anything that falls into the family of a carbohydrate. So if the earth grows it, that's a carbohydrate. Um, if it's a plant, it's a carbohydrate. Maybe that's a better way of describing it. And so it's going to have starches and sugars, which all 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 if blood sugar is too high for too long, that becomes very harmful to the body, so insulin comes in, um, and helps lower the blood glucose. And then having done its job, insulin comes back down.
8. SBSteven Bartlett
  So insulin comes out like a taxi and transports all the glucose in my-
9. BBDr. Benjamin Bikman
  Mm-hmm.
10. SBSteven Bartlett
  ... blood to various places around the body to store them?
11. BBDr. Benjamin Bikman
  Perfect. Perfect. Yeah, and the main-
12. SBSteven Bartlett
  So it's like a taxi for glucose.
13. BBDr. Benjamin Bikman
  Yeah. Yeah, that's right. It, that, you can sit, look at, it's a shuttle, it's a taxi saying, "Hey, glucose, come on in. I'm dropping you off at the muscle." So mostly, just as an interesting tangent of insulin, before I finish answering insulin resistance, insulin will open the doors for blood sugar to come in and dr- uh, 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, and the brain a little bit as well, other tissues will still respond to insulin, but they don't need insulin to tell it what to do with the sugar. It just takes it in. But even on those... Like the liver, for example. If the liver sees sugar driving by in a taxi, it just opens the doors and lets it in. It doesn't need insulin to come and tell it to let the sugar in. However, even at the liver and oth- 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 its forms as, as these kinda caloric-rich molecules. What to do with lactate, what to do with ketones, what to do with fats or glucose, what to do with pro- amino acids. So insulin will tell the body what to do with all of those things, but again, 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 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.
14. SBSteven Bartlett
  So say that again. So the-
15. BBDr. Benjamin Bikman
  Yeah.
16. SBSteven Bartlett
  ... insulin's coming past with the glucose inside it-
17. BBDr. Benjamin Bikman
  Well, no- not technically.
18. SBSteven Bartlett
  ... carrying it.
19. BBDr. Benjamin Bikman
  Yeah. But just to-
20. SBSteven Bartlett
  Yeah.
21. BBDr. Benjamin Bikman
  ... sort of go with your metaphor, but maybe to use another one, insulin comes and knocks on the doors. It's like the bouncer-
22. SBSteven Bartlett
  Yeah.
23. BBDr. Benjamin Bikman
  ... 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."
24. SBSteven Bartlett
  Mm-hmm.
25. BBDr. Benjamin Bikman
  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 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's just an obvious example because there's so much of it. You know, it is the biggest tissue on the average individual. Someone who's very obese perhaps now has more fat tissue, but even people who are overweight, most of us is muscle, so that's a good, it's a good tissue to look at. So part of insulin resistance is that of all the things insulin's trying to do, including lower blood sugar, it doesn't do it quite as well as it used to. Some of the cells or tissues of the body have become deaf to insulin's demands. Now, however, at the same time that's happening, insulin levels are higher, and that is really important. Um, and I'll, I'll 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, um, in concert. One, insulin isn't working quite as well as it used to in various places of the body. At the same time, insulin levels are higher, and that kinda 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. (clears throat) And so the body has adapted and it learns, "Oh, okay. Well, if one bouncer wasn't enough, let's send an angry mob of bouncers." And then the glucose, the muscle will start to open the door, and, and, and indeed it can. So those two problems go together. On one hand, insulin isn't working as well as it used to. That's what gives it the name insulin resistance. But there's another part that is equally present, which is that blood insulin levels are higher. Now, there's ear- um, earlier at the outset of the conversation, I mentioned that even infertility has an origin, has sh- has some degree of, um...... development because of insulin resistance, and it's a perfect example of both of these parts of insulin resistance where, 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 w- I was so struck by a title of a paper that had just been published which stated something like, "Is erectile dysfunction the earliest manifestation of insulin resistance in otherwise young, healthy men?" Now, what is the connection? It's because in a normal erectile function, in order for the man to have normal erectile function, he has to experience a pretty dramatic increase in the size of the blood vessels in his body. The 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, again, including telling blood vessels to expand. Now, unfortunately, in the case of this unf- uh, 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.
13:53 – 21:01
What Causes Insulin Resistance?
1. BBDr. Benjamin Bikman
2. SBSteven Bartlett
  Look, I don't wanna be insulin resistant.
3. BBDr. Benjamin Bikman
  No. No one does.
4. SBSteven Bartlett
  S-
5. BBDr. Benjamin Bikman
  No one does.
6. SBSteven Bartlett
  S- so tell me how it happens.
7. BBDr. Benjamin Bikman
  Yeah. Right. Yeah, so the origins are so important because it helps us understand why we've gotten into the situation we are, where it's the most common problem worldwide. There are two pathways to insulin resistance. So, uh, uh, two, 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, which is a more... I- 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, 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, uh, 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 any time 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 adrenaline/epinephrine, that are making you feel a little jittery. It's making your heart beat a little faster, you're a little more alert. Um, that all starts to play into a stress response. But what those two hormones have in 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 wanna be ready to run away or d- t-" That's the fight or flight kind of aspect to stress. And so they wanna push blood glucose levels up and they do very well. That, of course, puts them at odds with the hormone insulin 'cause 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 is... has those stress hormones elevated because of, say, sleep deprivation, that's a very effective way to, to increase cortisol, or they are taking too much... drinking too much caffeine. That is a way to increase epinephrine quite strongly. If both of those signals are too incessant or they're, you know, they're... they continue to be present and climb, then insulin has to work harder and harder and then we have insulin resistance. So stress is a cause of insulin resistance. But then next is inflammation. You, you know, you, you and I were commenting about... earlier about how, boy, there's a cold going around. People... It's flu season. Even then, if a person were wearing a continuous glucose monitor on the back of their arm measuring their glucose levels, they would see their glucose levels are much, much higher, like significantly higher, during the time that they're struggling with this infection. That is a reflection of insulin resistance. Insulin's having a harder time keeping the blood glucose levels in check. (clears throat) Anytime inflammation is up, insulin resistance will be up as well. Even in things like autoimmune diseases, there are reports in humans that document the degree to which someone has, say, active rheumatoid arthritis. Their, their joints are achy, uh, because of, of an autoimmune attacking of the joints. They will note, on some days, like every autoimmune disease, there is an ebb and a flow. Some days it's good, some days it's bad. And on the bad days, if you measure their insulin resistance, it is absolutely locked with the degree to which their immune system is turned on or off or higher or lower. So inflammation is another cause. And then the last one of the fast lane of insulin resistance is too much insulin itself. Now, the astute listener will realize the kind of circular thing I've just presented by invoking high insulin as a cause.... of insulin resistance because they will also think, "But wait a minute, Ben. You just said that high insulin is also a consequence of insulin resistance, that..." You know, back to the bouncer knocking on the, the, the door of the muscle cell, if one bouncer wasn't enough or one molecule of insulin wasn't enough, the body will say, "Okay, well, let's send 10 molecules of insulin." So high insulin is both a consequence of insulin resistance, but it's also a cause. And this is reflective of a fundamental principle in all of biology, that if there is too much of a stimulus, a cell, if it's capable, will try to become resistant to that stimulus. This would be, like, a, a funny analogy of in, in, in my h- in the Bikman home, my darling wife is home with the children. That is what she wants to do. She s- 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 'cause 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 gonna 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.
21:01 – 25:22
Can Insulin Resistance Become Chronic?
1. BBDr. Benjamin Bikman
2. SBSteven Bartlett
  If we can take it away. But if we can't take it away, does it become sort of chronic
3. BBDr. Benjamin Bikman
  Yeah, so at that-
4. SBSteven Bartlett
  ... in some cases?
5. BBDr. Benjamin Bikman
  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. 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's 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..." Um, 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." Um, and that's because it's not the mass of fat that matters most. It's the size of the fat cell that matters. This is why women, despite universally being fatter than her male counterparts, are healthier with regards to insulin resistance and every single metabolic problem. It's because women, as a result of her particular sex hormones, have more fat cells, but they're smaller. So she has more fat, but smaller fat cells. And small ph- fat cells are healthy, insulin-sensitive, anti-inflammatory fat cells. B- But the bigger the fat cell gets-... the more it initiates a cascade of events or a series of events that creates insulin resistance.
6. SBSteven Bartlett
  And am I right in thinking we have the same amount of fat cells for our whole life pretty much?
7. BBDr. Benjamin Bikman
  That's a really, really safe assumption for most people. Yeah, for most people the n- uh, a fat cell, um, sometimes students will hear that fat cells are immortal. That is not true, but they're long-lived. Fat cells will live about 10 years. And so typically by the time you... If you think of... If you look at a newborn during infancy, childhood, and puberty, the number of fat cells is going up, up, up, up, up. Once they finish puberty, so mid to late teens for a young woman, late teens or even early 20s for a young man, usually at that point the number of fat cells they have is going to be very
25:22 – 34:53
The Importance of Fat Cells Shrinking or Expanding
1. BBDr. Benjamin Bikman
  static.
2. SBSteven Bartlett
  This is something people don't really understand, and I actually discovered it from doing this podcast and speaking to so many experts about this, that we pretty much, especially as an adult, have the same amount of fat cells really regardless of what we eat.
3. BBDr. Benjamin Bikman
  Yes.
4. SBSteven Bartlett
  And it's actually just the fat cells we have shrinking-
5. BBDr. Benjamin Bikman
  Or growing.
6. SBSteven Bartlett
  ... or expanding.
7. BBDr. Benjamin Bikman
  Exactly. That's exactly right. Now, there are differences across-
8. SBSteven Bartlett
  Which by the way makes liposuction a pretty fucking bad idea.
9. BBDr. Benjamin Bikman
  In fact, it, in fact, it makes things worse. Please, let's make sure we come back to that.
10. SBSteven Bartlett
  Okay. I'll write down liposuction.
11. BBDr. Benjamin Bikman
  Because it really becomes... The person ends up, their vanity ends up really ruining their, their, their future metabolic outcomes. But there are differences across ethnicity, like, um, this is a little oversimplified but not much. On one end you'd have Caucasians, kinda Northern European Caucasians. On the other wind- end you'd have East Asians, like, uh, Chinese, Japanese, uh, Korean, East Asians. Um, and then if you look at that same spectrum of people making fat cells through their life, an East Asian will be making fat cells and then stop right about here.
12. SBSteven Bartlett
  About sort of...
13. BBDr. Benjamin Bikman
  So very few fat cells, relatively speaking, across all the ethnicities they have very few fat cells. A Caucasian on the other end of the spectrum, they went way higher. And so this guy, let's say American Ben versus Chinese Ben, overly simplified, but, but here we are. Um, so much of fat mass isn't the number of fat cells, even though American Ben has more, it's the size of the fat cell. So I could be the same percent body fat really as Chinese Ben, um, but that would just be because my fat cells were just that much smaller. But this is the problem then. If you have, let's say, American Ben and Chinese Ben both gained 10 kilos of pure fat over the next 10 years, very easily done, most people do that quite often, Caucasian Ben just doesn't look as good in his Speedo, um, which as a pasty Caucasian he's not going to look particularly good in that Speedo anyway. But I just am bulging a little more than I was before, but otherwise I'm healthy. My blood pressure's fine, my blood sugar's fine, everything's normal. Put that same 10 kilos of fat on Chinese Ben, hypertension, type 2 diabetes, fatty liver disease, infertility. Um, and that is because Chinese Ben had fewer fat cells to start with, and so those fat cells, as the body was told to store fat, those fat cells were getting much, much bigger much sooner. And the fat fat cell promotes insulin resistance very, very readily, and so that logically moves into this, the question of, 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, it is literally 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, how she looks and how thin she is. She learns that, "Wait a minute, I can eat whatever I want and all I have to do is not inject my insulin and I'll be as skinny as I want," and it works. It works so well that it's actually a formal eating disorder called diabulimia. So this, the fact that this exists is absolute proof 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 bo- for the very tissues of the body to know what it ought to do with energy, and so a fat cell will have energy all around it, and if it doesn't have insulin to tell it what to do, it won't do anything with it. Uh, uh, or maybe to make this more direct, back home in my lab my students, my students are growing fat cells in Petri dishes. These fat cells are swimming in a little sea of calories, lots of glucose, lots of fats, and yet they stay really small until we add insulin. The moment we add insulin into that little Petri dish, if we check those cells four hours later, they're immediately fatter. If we check them four hours later, they're fatter still. Now they know what to do with the energy they have. So with slow insulin resistance, it develops when fat cells get really, really big. It's like a, 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."
14. SBSteven Bartlett
  So insulin makes you fat.
15. BBDr. Benjamin Bikman
  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, uh, 10,000 calories of chocolate cake, they cannot get fat. Not only can they not get fat, they can't hold onto their fat, 'cause if there's no insulin to tell the fat cell to hold onto it or get big, it has to shrink. It's breaking down its fat. So the body goes into such a dramatic fat burning state in the absence of insulin that keeping fat becomes impossible. So the insulin signal is 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 gonna 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 gonna give me the bulk." And if you have one without the other, it is death.
16. SBSteven Bartlett
  So if I'm eating 2,000 calories and I have a different insulin sensitivity to you, say we both eat 2,000 calories-
17. BBDr. Benjamin Bikman
  Mm-hmm.
18. SBSteven Bartlett
  ... and I'm insulin resistant, doesn't that mean that I will...
19. BBDr. Benjamin Bikman
  You'll store more as fat.
20. SBSteven Bartlett
  Oh, okay.
21. BBDr. Benjamin Bikman
  Yeah. Yeah. So, so your body ... Now, it would partly depend on, there are people where you, you, if your f- if all of your fat cells had reached its maximum point then you're done, you're not gonna gain more fat.
22. SBSteven Bartlett
  Sure.
23. BBDr. Benjamin Bikman
  You're just gonna become more and more and more insulin resistant.
24. SBSteven Bartlett
  Okay, fine.
25. BBDr. Benjamin Bikman
  So you kind of start limiting yourself. But there are studies in humans to show that if you give humans isocaloric diet meals, so the exact same number of calories, but they ... and the same amount of protein, but you differ those meals based on the amount of carbs to the amount of fat, so let's say two meals, exact same calories, 2,000 calories or ... That's, in one meal that's too high. 1,000 calories in one meal. One version of this is the conventional way of eating, which is lower fat, higher carb; the other meal, same number of calories, but it's lower carb, higher fat. This lower carb, higher fat version will have a lower insulin response and they h- they will store less fat from that meal. Their meta- ... And someone would say, "Well, where do the calories go?" You can't d- this ... It's the laws of thermodynamics. You can't destroy energy. The metabolic rate will go up. So when insulin is low, if you have someone going a full day eating the same number of calories but lower carb calories, their metabolic rate will be almost 300 calories higher in that day.
26. SBSteven Bartlett
  And metabolic rate is the-
27. BBDr. Benjamin Bikman
  Yeah, that's the total amount of energy that it just costs you and I to just live.
28. SBSteven Bartlett
  Okay. So-
29. BBDr. Benjamin Bikman
  Your risk going through the day.
30. SBSteven Bartlett
  S-
34:53 – 42:17
What's the Evolutionary Basis of Insulin Resistance?
1. BBDr. Benjamin Bikman
2. SBSteven Bartlett
  It's worth ... Before we talk about how to keep my insulin levels low so that I can benefit from all the health benefits we've talked about, it's probably also worth just spending a little bit of time trying to understand the evolutionary basis of insulin resistance.
3. BBDr. Benjamin Bikman
  There are some theories that are very interesting that attempt to explain why is it that we became so fantastically different from, let's say, our closest animal relatives, other primates like chimpanzees or, or apes. What was the difference that had us become so different than them? One of the leading theories is a, is a theory called the expensive tissue hypothesis, and it actually does have something to do with ketones. In the expensive tissue hypothesis, as the theory goes, our earlier ancestors deviated in this kind of animal family line because we started eating more meat. We started eating food that was so nutritious, so nutrient dense, so loaded with good calories and all of the fats and proteins that we need, that it allowed two very distinct changes to occur in us compared to other primates. One, our intestines became significantly shorter. So if you compare the human digestive tract to any other primate animal, if, if we are a primate, um, then if you look at the intestines, they're fantastically different, particularly the large intestine or the colon, because our ancestors, as the theory goes, began eating meat, we didn't need the colon as much, um, a- because 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. (clears throat) So we started eating food that was so nutrient dense our colons 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 were shrinking, because we didn't need them to be so big, our brain was growing. And, and it's because it had so much nutrition, including ketones. So ketones are an extraordinary fuel for the brain. In fact, one of the reasons why a baby that is born premature will be more likely to have learning disorders later in life is because premature baby didn't have time to get very fat, and fat baby is healthy baby, and fat baby gets into ketosis. Let's say you and I were to, to fast straight for 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 bloodstream, 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. Um, that would be a normal glucose, and if you and I were to fast for 24 or so hours, we may get up to about 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 i- i- again, is so nutritious that it allowed our brain, 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 sh- seen in humans, that the less a human eats meat, then the smaller the brain becomes. The brain is so dependent on the nutrient density that comes from animal-sourced foods that it will suffer, um, when it doesn't get them.
4. SBSteven Bartlett
  Interesting. I mean, that's a controversial thing to say. (laughs)
5. BBDr. Benjamin Bikman
  It is, and you can cut it out. (laughs)
6. SBSteven Bartlett
  (laughs)
7. BBDr. Benjamin Bikman
  But it really is, it's a real thing. And why does depression go up so much when people stop eating animal-sourced foods? It's because you are depriving the brain of what it needs.
8. SBSteven Bartlett
  What is it exactly you're depriving the brain of in that situation?
9. BBDr. Benjamin Bikman
  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.
10. SBSteven Bartlett
  And you could supplement?
11. BBDr. Benjamin Bikman
  Absolutely.
12. SBSteven Bartlett
  Right. And that would-
13. BBDr. Benjamin Bikman
  Yes. Yeah, you can, but, but the, that, th- 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.
14. SBSteven Bartlett
  So is that the, the only evolutionary sort of hypothesis towards why we develop this insulin resistance?
15. BBDr. Benjamin Bikman
  Mm, oh, yeah. (laughs) In fact, it's funny that you bring the question up again, because I realize I didn't quite answer it that way. So insulin resistance, why would it exist at all? It would probably be a way for the body to know when it was needed to hold onto energy a little better. So now, I, I say that now and, and someone would think, well, but you just ... Why would I wanna hold onto energy in a way where it's causing hypertension and Alzheimer's disease and increasing the risk of heart disease? Not all versions of insulin resistance are negative. So there is, um, there is ... What all the insulin resistance that you and I have been talking about is pathological insulin resistance or harmful insulin resistance, insulin resistance that serves no good purpose 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 Ps 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
42:17 – 43:39
The Role of Insulin During Pregnancy
1. BBDr. Benjamin Bikman
  fat.
2. SBSteven Bartlett
  So in pregnancy, insulin's playing a role in growing the placenta-
3. BBDr. Benjamin Bikman
  It sure is.
4. SBSteven Bartlett
  ... the breasts?
5. BBDr. Benjamin Bikman
  Yeah, so in the woman, after she's finished puberty, the only other time of growth she'll ever have will be pregnancy. And, and so those are the two instances where the body has become insulin resistant to take advantage of the heightened scenario where it can grow.
6. SBSteven Bartlett
  Because the woman's body needs to, more fat.
7. BBDr. Benjamin Bikman
  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 sh- 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
43:39 – 45:05
What Is Gestational Diabetes?
1. BBDr. Benjamin Bikman
  born."
2. SBSteven Bartlett
  What is gestational diabetes?
3. BBDr. Benjamin Bikman
  Hmm, 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, um, who is very healthy, very insulin-sensitive at the beginning of her pregnancy. So glucose is normal and insulin is normal. Over the course of her pregnancy, she stays normal, healthy pregnant woman, which is to say she has physiological insulin resistance. She doesn't get diagnosed with gestational diabetes though, which means her glucose is normal. But to keep her glucose normal because she is insulin resistant but for a purpose, to help her body grow, her insulin levels are high, and then the glucose is still in a normal range. And then in some women, especially if she has a family history of type 2 diabetes, the insulin resistance goes too far. Now she has high insulin, like all pregnant women do, but she's not able to keep her glucose levels in check.
4. SBSteven Bartlett
  So if I'm eating loads and loads of sugar throughout pregnancy-
5. BBDr. Benjamin Bikman
  That will compound the problem. Absolutely. So then she will go from the normal insulin resistance of pregnancy into the insulin resistance of diabetes. So it really is like type 2 diabetes, but a microcosm of it, a mini version that was really instigated or initiated because of the pregnancy, combined with a bit of a genetic predisposition, combined with her eating the worst
45:05 – 45:59
Does It Impact the Future Baby?
1. BBDr. Benjamin Bikman
  possible way.
2. SBSteven Bartlett
  Does that then impact the future baby?
3. BBDr. Benjamin Bikman
  Oh, for sure it does. Yeah, so think about it's almost like the baby is devel- literally developing in a hyperglycemic, hyperinsulinemic environment. So the babies get- the baby gets hardwired to want to continue to exist in a state of high insulin and high glucose after the baby is born. And so yes, the offspring of mothers who have gestational diabetes are significantly more likely to gain weight and be chubbier or fatter than their counterparts, and to later develop type 2 diabetes. Yeah, a resounding yes.
4. SBSteven Bartlett
  I read in your book that these infants have a 40% higher chance to be obese and have metabolic complications-
5. BBDr. Benjamin Bikman
  Yeah.
6. SBSteven Bartlett
  ... in their teenage years and beyond.
7. BBDr. Benjamin Bikman
  Yes, I mean, a significant thing, and I- I say that with all of the sympathy I can for the mother who may be struggling with this, but it is certainly a motivation for mom to just be mindful o- of what you're
45:59 – 50:33
Women's Cancer Is Increasing While Men's Remains the Same
1. BBDr. Benjamin Bikman
  eating.
2. SBSteven Bartlett
  One of the things that- that I saw the other day on social media, which I wanted to ask you about, was this. I've got a picture of it here. Um, it was someone online that posted this photo and they said... well, this graph, and they said, "We need to figure out what's going on here." Um, this is the graph, I'll put it on screen for anybody that's watching, but also it'll be linked in the comment section below. Um, it essentially shows that over the last, let's say, 20 years, there's been a really significant rise in cancer amongst women, but when we look at cancer amongst men, it's pretty flat.
3. BBDr. Benjamin Bikman
  Mm-hmm.
4. SBSteven Bartlett
  Um, and this is cancer incidents by age and gender up to 49 years old.
5. BBDr. Benjamin Bikman
  Mm-hmm.
6. SBSteven Bartlett
  And I was wondering if you had any thoughts on why this is happening?
7. BBDr. Benjamin Bikman
  Yeah, yeah. Yeah, a few thoughts come to mind. Um, 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. Um, breast cancer is the main cancer for women, um, by far. And so if I had to guess, I bet almost all of this increase in cancer incidents is because of breast cancer. Why might that be going up? I would suggest there's probably a couple instances. One, um, although people might not appreciate this, is that one of the best ways for a woman to reduce her risk of breast cancer is actually having babies. It's very well known, um, very well documented that if a woman, um, has a fa- has babies and breastfeeds, her risk of, um, breast cancer goes down. So yeah, in fact it's very meaningful. I actually don't know, um, the reasons for it. It could be the changes in estrogens during lactation phase, but-
8. SBSteven Bartlett
  I've just- I've just actually done a quick search here to... I put a picture of that graph into AI and asked it the same question, and it said pretty much what you said. It said there's a rising breast cancer incidence according to Cancer Research UK. The other one that it came up with is obesity trends.
9. BBDr. Benjamin Bikman
  Oh, yeah.
10. SBSteven Bartlett
  ... because of-
11. BBDr. Benjamin Bikman
  I- I promised I was gonna talk about that.
12. SBSteven Bartlett
  Oh, yeah, yeah.
13. BBDr. Benjamin Bikman
  I- I wouldn't leave that. Yeah.
14. SBSteven Bartlett
  Sorry for interrupting there. Um-
15. BBDr. Benjamin Bikman
  No, no, no problem.
16. SBSteven Bartlett
  Uh, and then the other one was delayed childbearing.
17. BBDr. Benjamin Bikman
  That's what I'm saying.
18. SBSteven Bartlett
  Which is what you were saying.
19. BBDr. Benjamin Bikman
  Yeah, so as child rates- as childbirth rates are going down, it does...... increase the risk of breast cancer. Now, as, I'm a cell biologist, right? I like to understand the direct mechanism, and so as much as I invoke the perhaps lower rates of childbirth among women, I don't know the mechanisms, so I'm sort of loathe to describe it. The mechanisms I'm very familiar with are the metabolic, um, which is, if you take a breast tissue that is tumor tissue and compare it to... Like, if you take a breast tumor and compare it to the normal tissue right next to it, like that it would have shared its origins with, the cancer from the breast will have seven times more insulin receptors than the normal breast tissue. So the idea of this tracking quite nicely with obesity rates going up over the past 20 years, I wouldn't say that it's the obesity per se, but I would say it's the entire metabolic milieu, which is the insulin resistance, that as much as the high insulin is promoting fat cells getting bigger, that high insulin is also accelerating the growth of the tumor cells because again, the main, one of the main mutations in breast cancer is a sevenfold, so a seven times increase in the number of insulin receptors, and 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 wanna 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, it's very, very likely a consequence of the rising incidence of insulin resistance.
20. SBSteven Bartlett
  As
50:33 – 51:29
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1. SBSteven Bartlett
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51:29 – 1:05:34
Alzheimer's and Dementia Are on the Rise
1. SBSteven Bartlett
  You know, one of the big subjects you touched on at the start was the ide- was Alzheimer's and dementia.
2. BBDr. Benjamin Bikman
  Yes.
3. SBSteven Bartlett
  And I have heard several people on this podcast tell me that they think of Alzheimer's as type 3-
4. BBDr. Benjamin Bikman
  Mm-hmm.
5. SBSteven Bartlett
  ... diabetes.
6. BBDr. Benjamin Bikman
  Mm-hmm.
7. SBSteven Bartlett
  Worldwide there is a new case of dementia every 3.2 seconds. Um, it seems like, I don't know if this is true, but is Alzheimer's and dementia on the rise?
8. BBDr. Benjamin Bikman
  Oh, yes. Yeah, it is. In fact, it went from not being even on the radar to being a top 10 killer. Um, now, it's interesting how people even die from Alzheimer's disease. It's a very kind of vague death, but yeah, Alzheimer's disease is one of the top 10 diseases now, um, certainly in the West. Um, and, and I would argue it's because it has a metabolic origin. Now, one of the interesting things about Alzheimer's disease is we have spent billions of dollars on Alzheimer's research trying to identify the, the plaque. So, so just, just set the stage here so that people listening can appreciate this, this paradigm shift that's occurred in Alzheimer's research. Originally, and even in many people still, people thought that Alzheimer's disease is the result of these plaques accumulating in the brain. These kind of little proteinaceous little th- thick things that are preventing neurons from sending the signals, uh, throughout the brain for the brain to think and, and, and have normal cognition. And, and yet there are those of us, and I am proud to say I have long been one of them, who has said that the plaque-based theory doesn't make sense. We have had drugs that have been available for human use for years that have effectively 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 the, 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 very first published papers that implicated plaque as a cause of Alzheimer's disease were based on fabricated data. So the scientists who published those first reports that led to the entire theory that Alzheimer's disease is plaque-based were called out as fraudulent. And, and indeed all of it was fabricated. So the entire idea that Alzheimer... And, and we have spent billions of dollars on studies to try to s- how, determine how do plaques cause Al- uh, cause Alzheimer's disease? Why when we reduce plaques it doesn't appear to help the disease, because the plaques had nothing to do with it. That's just something that some brains have. Some brains have more of these little specks than other brains, and they don't contribute to Alzheimer's disease at all. Now, what did con- 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 diabe- type 2 diabetes. Now, I will say personally, I don't like the term type 3 diabetes because it makes it sound like it's a whole new version of diabetes. To say it more succinctly and accurately, it is simply insulin resistance of the brain, and the brain is a very hungry organ. It is in, what I teach as- as a trife- 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. (clears throat) 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, and you- you mind the gap, and the brain has an energy gap now, and- and where- where the brain needs, you know, an amount of energy, I- I'm kinda acting it out for those that are watching, but the brain has a certain energy demand that it needs. And if there's a lot of glucose in a healthy insulin-sensitive person, glucose will fill all of that need. But as the brain becomes progressively insulin resistant, it cannot get all of its energy from glucose, and thus there's an energetic gap. And in the absence of ketones, there's nothing to fill that gap, and the brain says, "Well, I don't have enough energy to keep functioning as well as I did before, so I have to reduce my function," which manifests as a reduction in the ability to think and process. In other words, cognition goes down. But what's so interesting is I just got finished describing a scenario that scientists refer to as brain glucose hypometabolism, or a reduction in the amount of glucose the brain is using. There are scientists that measured this. We don't in my lab because we don't do these kinds of techniques, but you can actually infuse people with a glucose that you can take pictures of and see how much the brain is taking it in and metabolizing it. In Alzheimer's disease, the brain is not getting as much glucose, so they call that a hypo or a reduction in metabolism of glucose. And as much as you and I are describing that scenario as relevant for Alzheimer's disease, you can essentially open up the book of neurological disorders and see the same thing. Depression has a brain glucose hypometabolism to it. Migraines have a brain glucose 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. Um, but that only can happen if the person is giving their body a break from the insulin long enough to actually start making ketones.
9. SBSteven Bartlett
  Really, really interesting on this point about 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- I was looking at there was how many people with Alzheimer's have- meet the criteria for insulin resistance, and some studies have it at 40%. There's a study I found here that has it at 70 to 80%, um, which I wanted to say, um, uh, exact percentages vary, but one example is a study in the Journal of Neurology in 2011 that found insulin resistance at approximately 40% of individuals with Alzheimer's. Um, but another study, uh, in Alzheimer's patients sometimes found it to be as high as 70 or 80%. For instance, research by Dr. Suzanne DiLamonte?
10. BBDr. Benjamin Bikman
  Mm-hmm.
11. SBSteven Bartlett
  ... at Brown University has drawn attention to the concept of type 3 diabetes.
12. BBDr. Benjamin Bikman
  Yeah. Again, I don't love the term, but I appreciate the use of it, which is- it does suggest a metabolic origin. But even- you look at those ranges, Steven, you'd say, "Well, one was 40, one was 80. Boy, what a difference." I suspect a lot of that is just how did they measure insulin resistance?
13. SBSteven Bartlett
  Right.
14. BBDr. Benjamin Bikman
  If they were looking at the glucose, like so many do, you're just going to miss a lot of people.
15. SBSteven Bartlett
  Yeah, it's quite hard to
16. NANarrator
  (pen clicks)
17. SBSteven Bartlett
  ... s- uh, I think there's different criteria, right, for how one defines someone as insulin resistant.
18. BBDr. Benjamin Bikman
  Well, the, yeah, and that's just, that's right. That's because there's not enough training, which is at the beginning of the conversation you asked my mission. One of my missions is to help people learn what to look for.
19. SBSteven Bartlett
  What do they need to be looking for?
20. BBDr. Benjamin Bikman
  Yeah, they need to be looking at insulin. So-
21. SBSteven Bartlett
  Is that easy to measure?
22. BBDr. Benjamin Bikman
  Well, it is technically easy to measure. It's just that we have- we don't have enough systems in place to allow bl- uh, uh, 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, 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, and Canada, um, where the system is such that they have said, out of ignorance, but perhaps well-placed or, or well-intentioned, they will say, "Well, insulin isn't a marker that matters." It is. And if you're measuring insulin resistance, just to put things back to where we had talked about it earlier, many people with insulin resistance have normal blood glucose levels. It's the insulin that's high. And so I would say if a person can get their insulin measured, get it measured. In US units, if it is anything above about 10 microunits per mL, 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-
23. SBSteven Bartlett
  And you could be skinny-
24. BBDr. Benjamin Bikman
  Oh, yes.
25. SBSteven Bartlett
  ... and have insulin resistance.
26. BBDr. Benjamin Bikman
  Yes, 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, it depends. E- even in, in young women, a g- 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 than the other group. So, so anyway, that's my way of saying, e- even if you look at yourself and think, "Well, I'm kind of lean. I'm not insulin resistant," you very well could be.
27. SBSteven Bartlett
  Okay, so I've got a friend who's a, a woman-
28. BBDr. Benjamin Bikman
  Mm-hmm.
29. SBSteven Bartlett
  ... who has PCOS.
30. BBDr. Benjamin Bikman
  Yeah.
1:05:34 – 1:10:03
Ethnicities and Their Different Fat Distributions
1. BBDr. Benjamin Bikman
  you.
2. SBSteven Bartlett
  Does your fat distribution also matter here? Because-
3. BBDr. Benjamin Bikman
  Oh, it does.
4. SBSteven Bartlett
  ... different g-
5. BBDr. Benjamin Bikman
  Yeah.
6. SBSteven Bartlett
  ... races, this research is telling me, have different fat distribution. It's saying that Africans have better fat distribution-
7. BBDr. Benjamin Bikman
  Mm-hmm.
8. SBSteven Bartlett
  ... lower visceral fat-
9. BBDr. Benjamin Bikman
  Yep.
10. SBSteven Bartlett
  ... and less metabolic risk because of that?
11. BBDr. Benjamin Bikman
  Yeah, yeah, yeah.
12. SBSteven Bartlett
  Caucasians, moderate fat cell quantity, more prone to subcutaneous fat accumulation which is-
13. BBDr. Benjamin Bikman
  Subcutaneous. Mm-hmm.
14. SBSteven Bartlett
  Which is, that's the fat around the organs, right?
15. BBDr. Benjamin Bikman
  Yes, so Caucasians 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 East Asian, all things equal, is putting much more fat there than they are subcutaneously. The advantage of subcutaneous fat is that it-
16. SBSteven Bartlett
  Which is the fat on the outside.
17. BBDr. Benjamin Bikman
  Yeah, yeah, so the s- the fat beneath-
18. SBSteven Bartlett
  Like belly fat.
19. BBDr. Benjamin Bikman
  ... 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.
20. SBSteven Bartlett
  And Hispanics have higher fat cell quantity, more visceral fat-
21. BBDr. Benjamin Bikman
  Yes.
22. SBSteven Bartlett
  ... and increased risk of obesity-related conditions.
23. BBDr. Benjamin Bikman
  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.
24. SBSteven Bartlett
  Right.
25. BBDr. Benjamin Bikman
  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.
26. SBSteven Bartlett
  According to 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 55 million in 2020, which I imagine is in part related to people living a bit longer-
27. BBDr. Benjamin Bikman
  Yeah, yeah.
28. SBSteven Bartlett
  ... than they once did as well.
29. BBDr. Benjamin Bikman
  Could be, although, although 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 overall 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.
30. SBSteven Bartlett
  There'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.
1:10:03 – 1:19:31
What to Do to Extend Our Lives
1. SBSteven Bartlett
  Bryan Johnson?
2. BBDr. Benjamin Bikman
  I have. I don't know him personally, but...
3. SBSteven Bartlett
  You've seen the documentaries and stuff made about him-
4. BBDr. Benjamin Bikman
  Yeah.
5. SBSteven Bartlett
  ... and the work that he's doing. What do you make of what he's doing to extend his age? 'Cause, you know, one of the subjects I think is linked to this is the idea of longevity-
6. BBDr. Benjamin Bikman
  Yeah.
7. SBSteven Bartlett
  ... and aging, and he's become a bit of a poster child for the subject of longevity.
8. BBDr. Benjamin Bikman
  Right, right. Well, I wanna address this 'cause this is a real person, so I wanna 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, 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? Uh, so all of the approaches to longevity nowadays rely on either correlational studies or basic research on 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." Well, a correlational study is by my estimation some of the weakest evidence that you can ever generate. A, 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 answer 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 determine diet.
9. SBSteven Bartlett
  So if I'm trying to extend my longevity-
10. BBDr. Benjamin Bikman
  Yeah.
11. SBSteven Bartlett
  ... trying to live longer-... then exactly what sh- should I be thinking about?
12. BBDr. Benjamin Bikman
  Yeah. Yeah. So my view on longevity is a metabolic view. No surprise. I am 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... Th- the birth of the modern longevity research, uh, at lea- if it didn't start, it was heavily influenced by the work of a woman named Cynthia Ke- Cynthia Kenyon, K-E-N-Y-O-N. Cynthia Kenyon was one of the kind of... She really did, in my mind, kinda 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, uh, um, for example, but it was compelling what she found. I think it was worms. She found, in worms, that if they restricted the glucose that the worms were eating, they would live 50% longer or some- some fantastic increase in the- how long the animals lived. That kinda 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 underexpressing 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.
13. SBSteven Bartlett
  Which is typically associated with long fasting.
14. BBDr. Benjamin Bikman
  Yeah. That's... Yeah. Yeah. In fact-
15. SBSteven Bartlett
  Uh-huh.
16. BBDr. Benjamin Bikman
  Yes. So that is partly why fasting has been so embraced within the fa- uh, longevity community. It's because if you can promote longevity or autophagy rather, if you can promote autophagy, the cell keeping itself cleaned out, 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 gonna 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.
17. SBSteven Bartlett
  You've, um, repeatedly talked about ket- ketosis-
18. BBDr. Benjamin Bikman
  I have.
19. SBSteven Bartlett
  ... and ketones.
20. BBDr. Benjamin Bikman
  Yeah.
21. SBSteven Bartlett
  We'll eventually get there. We're kinda teasing the audience a little bit, but I do wanna-
22. BBDr. Benjamin Bikman
  Yeah. We are. Yeah.
23. SBSteven Bartlett
  ... speak about it.
24. BBDr. Benjamin Bikman
  But rightly so. I mean, ketones are a very vilified, misunderstood part of the body. An- and to my great delight, um, it's getting- it's getting a sort of new appreciation.
25. SBSteven Bartlett
  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.
26. BBDr. Benjamin Bikman
  Mm-hmm.
27. SBSteven Bartlett
  And I wanna talk about the cons and the pros-
28. BBDr. Benjamin Bikman
  Mm-hmm.
29. SBSteven Bartlett
  ... 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.
30. BBDr. Benjamin Bikman
  Yeah.
1:19:31 – 1:22:15
Cholesterol: The Molecule of Life
1. BBDr. Benjamin Bikman
  this.
2. SBSteven Bartlett
  Sorry, the- they found that some of the longest living humans had high chole-
3. BBDr. Benjamin Bikman
  Yeah.
4. SBSteven Bartlett
  ... cholesterol levels?
5. BBDr. Benjamin Bikman
  That's right. 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, and so many- so much depends on it. Mitochondria, for example. Mitochondria have to have a cholesterol molecule in 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. Um, 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.
6. SBSteven Bartlett
  But there's good and bad cholesterol, right?
7. BBDr. Benjamin Bikman
  Well, that's... As the story goes, yes, and yet I think that's overly simplified. Um, where people will say LDL cholesterol is the bad cholesterol, and yet that gets included in these studies of longevity. So I, 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.
8. SBSteven Bartlett
  There is research suggesting that 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.
9. BBDr. Benjamin Bikman
  Exactly.
10. SBSteven Bartlett
  Which is bizarre.
11. BBDr. Benjamin Bikman
  Yeah. Well, you say that, and yet maybe our anti-cholesterol view is the bizarre one.

Episode duration: 2:43:50

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Intro

My Mission to Help with Chronic Diseases

What Is Insulin Resistance?

What Causes Insulin Resistance?

Can Insulin Resistance Become Chronic?

The Importance of Fat Cells Shrinking or Expanding

What's the Evolutionary Basis of Insulin Resistance?

The Role of Insulin During Pregnancy

What Is Gestational Diabetes?

Does It Impact the Future Baby?

Women's Cancer Is Increasing While Men's Remains the Same

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Alzheimer's and Dementia Are on the Rise

Ethnicities and Their Different Fat Distributions

What to Do to Extend Our Lives

Cholesterol: The Molecule of Life

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