The Joe Rogan Experience - #1267 - Gary Taubes & Stephan Guyenet

Episode Date: March 19, 2019

Gary Taubes is a journalist, writer and low-carbohydrate diet advocate. Stephan Guyenet, PhD, is a neuroscientist and is also the founder and director of Red Pen Reviews.

four three two one and we're live all right so to set this up um when gary was on last gary tobs stefan how do i say your last name stefan dna dna yeah dna it's like DNA. Like DNA, but with a G. Right. Got it. Okay. When you were on last, Stephan had some opposition to some of the things that you were saying. We talked about getting him on and you on together. We finally pulled it off. There was a lot of wrangling.

There was a lot of back and forth and cat wrangling, but we got it. We're here. Give me your position on – this is all for folks listening, this is all about obesity and the mechanism for obesity. Is that fair to say? Yeah, yeah. So essentially, the main points that we want to talk about today are- Try to keep this a fist from your face.

Okay, sure. Just pull it, you can move it around. What causes obesity and what causes insulin resistance resistance which is behind a lot of our um chronic diseases that are common in society and please uh give us your background yeah so i have a bs in biochemistry a phd in neuroscience after After getting my PhD in neuroscience, I went on to study the neuroscience of obesity at the University of Washington, and particularly the brain circuits that regulate body fatness. Hopefully we'll get a chance to talk about those today. And then I went on to become a science consultant, science communicator, and write a book called The Hungry Brain that is my attempt to explain for a non-specialist audience what causes obesity.

And yeah, so that's my background. Now, what is your disagreement with Gary's position? Everything. Everything? Yeah. So how about I just, can I start by explaining what I believe causes obesity? I'm going to be long-winded here, is that okay? It's okay, go right ahead.

We have hours. Okay, cool. So first, a little bit of housekeeping. I'm going to be citing a lot of evidence today, and so I want- Just please bring this up to your face. Okay, sure. Just move it around, because you want to sit back. How's that?

Perfect, beautiful. I'm going to be citing a lot of evidence today, and I want people to be able to follow along at home. And so I've put many of the references that I'm going to be citing on. Do that so it doesn't cover your face. Okay. There we go. All right. I put a lot of the references that I'm going to be citing on my website,

stephangeana.com, or if you don't feel like spelling my name, you can go to wholehealthsource.org. And I have a numbered list of topics there. And I'm going to be calling out numbers. Just scroll down to the number that I referred to, and the references are all there. Second thing I want to say that I want to be really clear about today is that I'm not here to be the anti-low-carb guy. Okay. I'm not here to be the anti-low-carb guy.

I think low-carb diets are a valid tool for controlling body fatness and controlling blood sugar. I'm not here to talk anybody out of being on a low-carb diet. What I am here to try to talk people out of is some of the mythology that has accumulated around the low-carb diet. Okay, so I want to get started with an analogy to help people understand why the brain is important in obesity. So imagine you're an alien coming down from outer space, and you want to understand what's going on on Earth. And you notice that on the highway, some cars are traveling faster than others. Some cars go faster, some cars go slower, and you want to figure out why. And so you go and you start studying the tires of the cars because obviously the amount of force that is exerted by the tire onto the asphalt

is the thing that determines the speed of the car. We know this. This is just physics. And so you study the tires and you study the tires and you study them and you never figure out why some cars go faster than others. Now, why is that? The reason is that you're studying the wrong part of the system. If you want to understand why some cars go faster than others, you have to understand the part of the system that regulates speed and that is the person behind the wheel. And so in this analogy, the tires are fat cells and the person behind the wheel is the brain.

There has been tons of research on fat cell biology, on what factors put fat in fat cells, what take it out. There's been tons and tons of research on that. And it's intuitively obvious that we should be studying that to understand obesity, right? But in fact, all of that research has yielded very little insight into why some people are fatter than others. That's because it's the wrong part of the system to study.

Fat cells do not regulate the size of fat cells any more than the tires on a car regulate the speed of the car. The thing that regulates the size of fat cells is the brain. So let's talk about, first I'll give you a little framework for thinking about this. The brain evolved over about 600 million years to promote the survival and reproduction of our ancestors. And over the course of that time, we evolved all these different brain circuits that have specialized functions. They generate our hunger and our cravings and our fullness feelings. They generate our eating behavior, what and how much we eat, and they

actively regulate the amount of fat on our bodies. And that's one of the things I want to talk about. And all of these circuits evolved, and these are non-conscious, by the way. So you don't decide you want to be hungry. You don't decide that you want to have a craving. These are things that bubble up from non-conscious parts of your brain that you don't control. So these circuits are calibrated to an environment of our ancestors, not the environment we're living in right now. So these circuits all evolved to function optimally in the environment of our ancestors, promote the survival and reproduction of our ancestors. So what happens when you put these brain circuits in the modern environment where you have abundant, calorie dense, tasty foods rich in carbohydrate and fat is these same brain circuits push us to over consume and they push our bodies to accumulate and hold on to fat.

And then what you see as a result is the three hallmarks of obesity. First of all, the obvious, you see elevated body fat mass. Second of all, you see elevated calorie intake. People with obesity consume more calories than people who do not have obesity after correcting for height and sex and physical activity level. And third, you see that people with obesity defend their higher level of body fatness against changes. And so there's actually a regulatory change that happens. It's not conscious defense. You know, they're not trying to remain obese. It's these body fat regulatory circuits. And this is where Gary gets it right, is that people with obesity are not just lean people who eat more calories. There's actually a change in the regulatory activity that regulates body fat in the body.

And we can get back to how that happens, but I'll just leave it there for now. So up until this point, I've basically just been telling a plausible story, right? I mean, I haven't actually cited any evidence yet to support that my story is correct. And so let's get into that. Let's talk about what some of the evidence is that supports this idea that I've just laid out. So I want to start with the genetics of obesity. I think this offers some some can i interrupt for one second uh as long as it's very brief just a question i don't i still don't quite understand what the model is okay i understand the dysregulation of the brain environment if you don't understand

the model how about i lay out how about i finish laying it out and then you can ask a question because i may answer your question over the course of continuing. So let me just finish. Okay, so now the genetics of obesity offers us a lot of insight into the biological mechanisms that drive differences in body fatness in the general population. So you get these studies, like the most interesting studies are the genome-wide association studies. like the most interesting studies are the genome-wide association studies. They get hundreds of thousands of people together, and they sequence or they measure all these markers in their genomes,

and they figure out what parts of the genome make some people fatter than others. So if you have version A in this particular location, you end up a little fatter than if you have version B. And when you look at all the places where this is happening, you can see the genes where it's happening in. And that tells you, if you look at what those genes are doing, that tells you what the mechanisms are that underlie everyday differences in body fatness in the general population. And so to kind of warm ourselves up, let's start by talking about height genes. So height has a strong genetic component, so does body fatness. And researchers have figured out a lot of the genes that underlie

differences in height between people. And when you look at what those genes do, they tend to be involved in the growth and development of the skeleton and the connective tissue, which is what you would expect, right? Because growth of the skeleton determines your height. So genes that determine diabetes risk, type 2 diabetes, are all about insulin sensitivity, all about insulin secretion, and the function of the insulin-secreting pancreas, which is what you expect because diabetes is a disease that is all about insulin. So these studies are really good at getting at the underlying biological mechanisms that are driving these phenomena.

So what do these studies have to say about obesity? If Gary's model is correct, we should see a bunch of genes popping up related to fat cells and insulin. If my model is correct, we should see a bunch of genes popping up related to the brain. And in fact, that's exactly what we see. The genetics of obesity are overwhelmingly related to differences in brain activity between individuals. And okay, so that's one piece of evidence. Another piece of evidence, there are five FDA approved weight loss drugs. Four of those act in the brain. One of them reduces dietary fat absorption in the digestive tract. There are no effective

fat loss drugs that I'm aware of that target insulin or fat cells. Third piece of evidence. If you look at, some people get really unlucky in life and they end up with these horrible genetic mutations that, you know, knock out some biological pathways. Some of these people end up with extreme obesity. People and also animals, we see this in mice and rats, just occasionally you get unlucky and you get really, really fat. And researchers have been cataloging what are these mutations. When we find people who are genetically really obese, what are these mutations that are making them fat? What is the biological mechanism that's getting screwed up that's making them fat? And what they've found is that all of these

mutations that they've identified to date, a number of them are occurring in the leptin signaling pathway. And this is, the leptin is the primary fat-regulating hormone in the body. Gary avoids this, never talks about this in his writing, but leptin is the primary fat-regulating hormone in the body, and these mutations either knock out leptin, they knock out leptin receptors, or they knock out the leptin response pathway in the brain. And so that's the third piece of evidence. Okay. So now we haven't really gotten around to talking about what it is exactly about the bad interaction that happens between our ancient

brains and the modern food environment that causes us to become fat. We've established that the brain is central to obesity, but we haven't really established what it is exactly about that interaction. Why does our modern food, why does our modern environment promote obesity, right? So, basically, there are three different ways that I'm going to look at this from. But first, I want to say that probably the best way to answer this question is to start with the question, what is the most fattening diet in the world? What is the diet that is more fattening than any others? And the answer to that is it's human junk food. In a variety of non-human species and humans, it's human junk food that is variety of non-human species and humans it's human junk food that is more fattening than any others and i'm going to skip over some of the research here that

demonstrates this by the way i haven't been calling out numbers here okay let me call out some numbers um reference number two on my website is those genetic studies. Reference number one is the obesity drugs. Reference number six is those spontaneously occurring genetic mutations. And now I'm talking about reference number 52. So I'm going to gloss over some of the individual research because I'm being long-winded here, but essentially what you find is that this stuff is really fattening in animals, many different species. It's super fattening in humans, calorie dense. When you create an environment with abundant, easy, calorie dense, tasty foods, rich carbs and fat, you see this dramatic overconsumption and fat gain across many species,

including humans. And what you find in the research is that the sugar and the carbohydrate cannot explain that. They're part of the effect. Yes, they explain part of it, but you cannot replicate that effect by only feeding sugar and carbohydrate. You can't replicate it in animals. You can't replicate it in animals. You can't replicate it in humans. When you say you can't replicate it, you mean you can't replicate obesity? What do you mean? Yeah, that's right.

You cannot cause the same degree of fat gain, the same extent of fat gain, the same extent of overconsumption using only sugar and carbohydrate that you can cause with a variety of calorie-dense, palatable human foods. You can't fully replicate it with sugar and carbs. You cannot fully replicate it with fat alone either. If you put those, and we can get deeper in this if you want. But I'm confused. So you're saying that the diet that causes the most obesity is what we think, right? This human junk food diet, rich in sugar, simple carbs, bullshit diet, right?

You're saying that you can't replicate that with just sugar and carbs? You cannot fully replicate it. Fully in what sense? What I mean is that if you just feed, if you just increase sugar intake in animals or in humans, you do get weight gain, but it is modest compared to what you get when you put people around a variety of calorie-dense, palatable foods rich in carbohydrate and fat. Similarly, if you- That's very confusing. How's that? Because I'm not sure exactly what you're saying. You're saying if you give people this calorie-rich sugar diet of junk food,

you will make them gain weight, but not as much weight as what? So what I'm saying is that if you, if you give people or animals the, the actual human junk food with all the carbs and fat and everything, they gain a lot more weight and a lot faster than if you just give them a diet that's high in sugar and high in refined carbohydrate. And what that shows is that the sugar and the refined carbohydrate cannot fully explain the effect, can't fully explain why those foods are fattening. See, this is where I'm confused. No, I don't see what you're saying.

Because you're saying if you give people the diet of American junk food, you get not as much of an effect if you give them just the sugar and the carbohydrates? Correct. Is that what you're saying? Yep. So, but what are you giving them when you're giving them the diet of junk food? You're giving them sugar and carbs. Well, for example, in animals, no, it's different. Because if you think about human junk foods, generally those foods contain fat and carbohydrate and salt and all kinds of other things.

So, it's more. It's more than just carbs, right? Well, it's a lot of soda, too, right? There's no sugar. Yeah. It's just sugar and it's just okay just sugar and that so i'll get in more detail so the ways that you can do this you can add sugar just sugar table sugar to the feed of animals that's one way to do it or you can add it to their

drinking water sometimes it's a little bit fattening sometimes it's not it's not that fattening in animals um in humans you can ask them to drink sugar-sweetened beverages that are just sugar, and you can see what happens. And people will gain weight. Or you can tell them to stop drinking sugar-sweetened beverages, and you can see what happens. People will gain weight. They will lose weight, suggesting that that is part of the explanation,

but it's a much smaller effect Than you see with this full palette Of these foods that contain carbs And fat and all this other stuff So you're saying Obviously there's more calories right If there's carbs and fat and all these other things Correct if you think that calories matter Then we agree

Well for sure it matters right Gary doesn't think it matters You don't think it matters I think it's the wrong way to think about it What do you disagree if anything with what he said so far? Well, so far what he said hasn't been particularly revelatory. I think we have to step back for a second because, you know, while the low-carb community might have a better understanding of where we disagree I think the greater community that Joe reaches might not so

fundamentally what Stefan's saying and what the research community's saying and the conventional thinking in this field is that the brain and correct me any point I get this wrong but the brain regulates does the fundamental job of controlling how fat we are. And the way it does it is by controlling or miscontrolling our intake and our expenditure, and the difference ends up in fat tissue. Is that fair to say for the most part? Primarily intake, but yeah. Yeah. So Stefan has a brain-centric view of the universe and the community at large does as well. So if we go outside and we walk down

Ventura Boulevard and we see someone who weighs 400 pounds, they've clearly taken in more calories than they should have over the course of their life. They've clearly taken in more calories than they should have over the course of their life, and it's been stored in their fat tissue. And Stefan says, I think would say that the problem is in their brain's ability to regulate intake to expenditure. Is that correct? Yeah. Okay. And let me, I have to fix my headphones.

How are we going to do this? I'm getting feedback when I talk. You're getting feedback? Yeah, it's just weird. Could be the, hold on one sec. For those who don't know, I'm hearing impaired, as they say kindly. My kids would say deaf as a post. Is that better?

So I took off my hearing aids. That's a little better. Okay. So what I've been arguing, so I come along, my background, I'm a journalist. I'm an investigative journalist with a science background. Okay. That's what I do. And I'm curious. And I've got a lot of, you know, my first two books were studying what's called pathological science, which is about people who got the wrong results in science, because a lot of times scientists do. So I'm very sensitive to this.

And as I was doing the research for my first book, which took five years, what I noticed when you take a historical perspective is that the research community studying obesity was very focused on the brain. They just assumed that fat people are gluttons. And I'm going to use some socially unacceptable language because in part that's how they thought about it. In fact, when you read the obesity literature from the 40s and 50s, it's shocking the way these people talked about people with obesity

and the assumption was that they're gluttons or they're neurotic or they're anxious or they're just, you know, but it was all brain-centric. And when they got to the 1960s, the field was being run by psychologists and psychiatrists who were trying to get people with obesity to eat less. And my favorite example is one team that was trying to get, they got the wives to stop having sex with the husbands if they didn't lose weight every week. And that would motivate them. I think even you point out that sex is a greater motivator in your book than tasty foods. It didn't work.

I didn't say it was greater, but I said it was on par. On par. So, and I'm going to just read you, I won't read you that. So there was this, while the obesity research community is focusing on the brain, there were people studying fat metabolism. Endocrinologists, they study hormones and hormones-related disorders, saying that fat storage and fat mobilization, the burning of fat in the human body, and fat mobilization, the burning of fat in the human body is controlled by this very diverse set of hormones and enzymes and the nervous system is involved in well. And our body does a very careful job of basically orchestrating how we use fuels after we eat. And the implication was,

and I think Stefan kind of stepped into this with the very first thing you said, so the assumption was obesity is a disorder of excess fat accumulation. So today, when you read the literature, the articles will often say obesity is a sort of energy imbalance. You take in more calories than they expend. There were still the best scientists in the field, the best physician scientists would say, look, obesity is a sort of excess fat accumulation. Let's look at what regulates fat accumulation in the human body. Some people are programmed or dysregulated to store more fat. And if they store more fat, their behavior is going to respond. They'll be hungrier, they'll eat more, they'll be gluttons, all these things. So it was switching the causality. Instead of the brain determining energy balance and that determining fat accumulation, the idea was

sort of, let's see what regulates fat accumulation, if that's dysregulated. If I give birth to a daughter who weighs 100 pounds at age four, I'm not going to worry about how much she eats and exercises. I'm going to worry about how much he eats and exercises. I'm going to worry about what's going on with fat accumulation in this young girl that her body is just as if you give a, you know, if you have a child who's six foot eight when he's six years old, you're not going to worry about how much he eats and exercises. You're going to worry that he's over secreting growth hormone. So the idea, basically what I've done, my role in this is to say, look, in this vitally important period in the 1960s and

1970s, when obesity researchers came to understand, fat metabolism researchers came to understand the regulation of fat cells, the obesity people were convinced that the problem was in the brain. And those obesity people eventually grew into the world that Stefan got his PhD in, this neurobiological world where you study what's happening in the brain and you ignore what's happening in the fat cells and fat mobilization and fatty acid oxidation and fat stored. And when you look at that, you find a whole world of places in which people can be predetermined, you know, be driven to be fat. So, for example, when I was in high school, senior year in high school, I weighed 195 pounds and I played football.

Senior year in high school, I weighed 195 pounds and I played football. And my brother, two years older, weighed 195 pounds his senior year and played football. My brother never got more than 195 pounds. And I went up to 240. We both ate as much as humanly possible, you know, as you could imagine. That's what high school athletes do. My brother was always lean. I was always chubby. My brother stayed lean and became an endurance athlete.

I became a football player, and I lifted weights. I put on muscle easily, and I fattened easily. He didn't. The conventional wisdom would be the reason I went to 240 and he never got to 195 was that my brain was different than his. My argument is our bodies were fundamentally different. So if I see somebody walking down the street who weighs 300 pounds, I don't worry about, I don't think about what the problem is with her brain regulating intake and expenditure. I think about why is her body driving her to be 300 pounds.

So that's, I think, kind of the fundamental difference. And is it the brain that can't do the job, or is it the body that can't do the job, and the brain is responding to what's happening in the body? Yeah, is this a reductionist perspective? Because, I mean, isn't it a holistic, I mean, holistically, you're looking at the entire machine of the human body, the idea that the brain is somehow or another separate from the body is – I'm not saying it's separate.

The question is, is the brain driving what's happening in the body or is it responding to what's happening? Yeah, so – and the brain, of course, does respond a lot to what's happening in the body, and we can talk about that and how that works. works. But, you know, I think it's, we can tell stories, but the things, the thing that differentiates a story that's true from a story that is not true is evidence. And so, you know, you talk about the difference between your brother and you, this is where that genetics evidence comes back in that I was talking about. Your brother and you only share half of your genes. We know that genetics has a strong impact on who has a greater susceptibility to body fatness than others. And we also know what the genes do that underlie those differences.

Wait, wait, wait. I'm not done, Gary. Let me finish. I just want to read something from your book. Those genes. Can I read something from it? Nope, nope. Not right now.

I'm in the middle of saying something. Those genes are primarily related to differences in brain function. That is what the genetics say. And so that suggests that the reason why you had a greater propensity than your brother to become fat probably has to do with differences in genetics that relate to brain function. That is what the research says. Isn't it very difficult to parse out when you're talking about two 17-year-olds that weigh exactly the same amount?

Like, how do we know how much they consumed in calories? I mean, we don't have any studies. We don't have any tests. No, but I mean, I can guarantee you we both ate as much as humanly possible. Right, but maybe you ate more. Actually, my brother, who never got over 195, and I apologize for bringing you up on the air. I know you don't like that.

Used to say that he never gets stuffed he just gets bored of eating after a couple of hours okay okay but maybe even though like maybe if you looked at it scientifically you ate more than him or maybe you ate more sugar no i clearly more carbs well so that's a difference. So those are the two hypotheses. One hypothesis is my body, and this is what Stefan is talking about. So I want to, just the thing I wanted to read, how much, I'll ask you the question, how much of the variation in human obesity do those genes explain? So if you look at the genetics of... No, I didn't ask how much is genetic.

Gary, I'm answering your question. Once he starts talking, yeah, you got to ask how much – Gary, I'm answering your question. You need to let me – Once he starts talking, yeah, you got to let him talk. Yeah, please, Gary. So if you look at the genetics of obesity, what you find is that from twin studies and family studies that measure the overall contribution of genetics, about 75% of the differences in body fatness between individuals is due to genetic differences between those individuals. So, you know, 1995 America, if you just take a cross-section of people and you measure how much is genes, how much is environment, about 75% is genetic.

Now, we've only identified a small proportion of the specific genes that underlie the propensity to obesity. And so if you look at the percentage that we have specifically identified, it's very small, and that's what I refer to in my book. How much? It's like right now I think it's up to about 10%. It was 3% when your book was published. Yeah, that's correct. So you're saying they did 7%?

Absolutely, yeah. The latest, yeah. Actually, let me cite the study there. No, just a second. I'm going to cite this study. Just a second. I'm going to cite this study. The study is under reference number two.

So you can go check that out. It's about 10%. And these genetic studies are advancing very quickly, and that's why in the three years since I wrote that, we have explained a lot more than we did at the time that I wrote that. And so we have a portion of these genes identified. And what we're seeing is that most of that portion that we have identified relate to brain activity. And so that tells us that primarily the differences between individuals that determine differences in body fatness is about differences in brain activity. No one should be shocked about this. The brain generates all of our eating

behavior. It generates all of our physical activity behavior, and it actually regulates body fatness. No one should be surprised by this. I am. And I was. And how are you surprised? Well, again, I disagree with virtually everything. But let's begin with – I have to track back now. Okay, so drugs that explain obesity, 10%. With the argument that I was making and the argument I continue to make, imagine if – take Stefan's car medical – You see Stefan. He says Stefan. You say Stefan, he says Stefan. You say Stefan, right?

It's okay. I'm not offended. It's okay. But I mean, just so people don't get confused. Thank you. If you take Stefan's car analogy, and somewhere in the 1970s, I've used the car analogy for this too, but I don't think it's as appropriate. But one way to think is somewhere in the 1970s, the aliens didn't notice that there were humans driving the car. So now they're trying to solve the problem without the humans involved. Why do some cars drive faster than others?

And they come up with all kinds of hypotheses, and some of them can explain it. Even when they interpret the hypotheses, one of the common problems in science is called intellectual phase lock. So what I've been arguing is, in effect, the obesity research community left out of its research 1960s era endocrinology, the hormonal metabolic regulation of fatty acid metabolism, oxidation, burning. regulation of fatty acid metabolism, oxidation, burning. And as such, when they did it, pretty much everything they've done since has been interpreted incorrectly, just like the aliens would interpret the car problem if they never noticed the humans. And leptin is a good example. So leptin is discovered in 1993. And when leptin is discovered, obesity becomes sort of a legitimate field of science. Until then, it's a bunch of actually mostly psychologists studying it, and now it becomes a subdiscipline of molecular biology, and all the molecular biologists jump into the field.

And they assume that what leptin does is control the brain. It signals how much fat is available. brain. It signals how much fat is available. It's some kind of satiety or fuel deficiency hormone. And as such, they study the brain and they study the action of leptin in the brain. Now, in 2002, Jeff Friedman, who gets credit for discovering leptin, perhaps incorrectly, credit for discovering leptin, perhaps incorrectly, publishes a paper in the journal Science. It's saying perhaps as much as two-thirds or more of what leptin does is done in the periphery, in the body. And what leptin does is it's a hormone that sort of is secreted in response to how much fat you've accumulated. And then does it stimulate the brain to tell you to eat more or less, depending on how much fat, or it also works in liver cells, which were the cells that we're studying, and the

assumption is it probably does in all cells, to tell your cells to burn fat. So it makes perfect sense. If there's fat available in the fat cells, now you've got a signal telling, sort of influencing the other cells of the body to burn fat. So now you've got a hormone that could work in the periphery, below that neck. Or it could work above the neck, but you've got a community that's almost exclusively studying in the head. They don't know there are human drivers down here. So that's what they do. So even in this world, I think I know the genome paper. Stefan is probably referenced on his website.

There have been a number of them, but yeah, that's the most recent. The Harvard group? I don't remember. So they had two papers, because this is what you cited in the article you co-authored with Rudy Leibel. So they have two papers. One is genes associated with obesity papers. One is genes associated with obesity, and one is genes associated with body type. So with body type, they're all below the neck. They're all fat metabolism, basically, and the genes that aspects of your body that you would

expect to be controlled. Like when you build up muscle and you have to take in excess energy to do it, it makes you hungry. I don't think your brain is regulating how much muscle you're building other than your drive to go to the gym. Basically, your body is responding to the stress on the muscle, all the things you do in the weightlifting. It's all below the neck. So the argument here is, again, simple. When these people looked at body type, it was insulin-regulated genes, for the most part, growth hormone, all these things. When they looked at excess body fat, they decided they were in the head. But the question is, when they looked, they're programmed to think that excess body fat is caused by overeating. So they look in the brain. Did they do the same kind?

And I was going to call the researcher involved. I never got around to doing it, saying if body type, body shape is determined by these genes, then doesn't it make sense that excess variations of body shape are going to be determined by the same genes? And did you do the same kind of searches? I don't actually know how they determine where the genes work. It's the same kind of searches. They just came up with different sets of genes. So they didn't start with any assumptions.

They were just finding whatever was there. No, but the question is where the genes work. So there's a common phenomenon in all this. Like with leptin, a gene that everybody thinks about working in the hypothalamus seems to work in every cell in the body. Can I respond to that? Wait, let me finish talking. Because you say this in your book.

You say this in your book. Yeah, go ahead. I'm prepared to respond whenever you're done. Okay. In your book, you say that genes work. You know, the body is very, basically, it puts different mechanisms to work in many places as it can. And there are these homeostatic feedback loops. You know, something happens, your whole body has to respond. So a gene that might work primarily

on one cell is scattered all over the body because every cell, and it'll do different jobs on different cells. But if you think that the problem's in the brain, that's where you look. So you get this kind of intellectual phase lock where that's what we do, that's what we study. A neurobiologist studies the brain. Daniel Kahneman, Stefan likes to cite Daniel Kahneman as well, had this concept, what you see is all, he's a Nobel laureate, cognitive psychologist, what you see is all there is. And basically, if you're studying the brain, that's what you look at. If you're studying the gut, and so we all get trapped into that on some extent. And what I'm saying is even in these studies, so Stefan wrote a book about the hungry

brain that is supposed to be about obesity. But in fact, you never mentioned anything about the metabolic regulation of fat accumulation. It's just not there. And I would argue, it has to be there, even if it's wrong. If it's not there, the absence of it, you can't talk about leptin without talking about what it might be doing in the body. talk about leptin without talking about what it might be doing in the body. You can talk, you know, so there's a, and it's put me in a very odd position. So Stefan is kind of the defender of the orthodoxy, and I'm the one who comes along and says, look, you guys just, you missed it. You screwed up. You had psychologists and psychiatrists running the field when the endocrinologist solved it, and then you discovered leptin, and it became a molecular biology problem.

And you're now divorced from the very simplest observations about obesity. So we can do huge genome-wide association studies. They sound remarkable. But if I were to ask a simple question like, why is it I get fat here? You know, the love handle thing? It's in the back with me. It's not in the front, but it's here and not here. I don't see what the brain has to say about that.

Okay, so as you mentioned, there have been different genetic studies that have looked at body fat distribution versus total body fatness. So total body fatness is what we're talking about when we're talking about obesity. Body fat distribution is what we're talking about when we're talking about the fat being on your hips versus on your wrist. Now, what we see is different sets of genes that come up. So body fat distribution, we actually see insulin-related genes. So people that have a central body fat distribution, so body fat around their waist, tend to have these insulin related genes that are driving that. But when you look at

total body fatness, the thing that causes obesity, what you see is that those genes are dominated by the brain. And the really cool thing, the point I want to make about the genetics research is that it's... 10% of those genes might be dominated by the brain, if they looked. Come on, Gary. It is unbiased. That's the really cool thing about it, is that they're just, this is whatever genes are popping up. These studies do not care about what you believe about what causes obesity. This is just whatever genes are popping up. So, it's unbiased. And that's what they're saying. And I'm not done here, Gary. Now, I want to talk about, you mentioned, Gary,

that maybe leptin is having important actions, not just in the brain, but in the body. First of all, I'm glad, I'm flattered that you read my book and I'm glad that you acknowledge the existence of leptin now. This is good. But now you say that researchers

focus on leptin actions in the brain because we're phase locked and we can't get out of our, you know, blinders of thinking about it in terms of the brain and that that's why we focus on leptin action in the brain. The real reason we focus on leptin action in the brain is because it has been demonstrated that its effect on body fatness are via the brain. There are actual experiments demonstrating this, and I'll explain how these experiments work. This is all in the scientific literature. So if you knock out the leptin receptor only in the brain or only in the hypothalamus you get obesity so that is what tells us that actually the brain is the key site of action particularly this tells you it tells you a key site of action please let him talk he let you talk yeah and that's it so i mean you get the

same obesity if you knock leptin out of the brain, and particularly out of the hypothalamus, that you get if you knock it out of the whole body. So, that shows that the brain is the site of action that is controlling our appetite, that are controlling our metabolic rate. We have many of these neural populations worked out. In mice, we understand these systems so well. We can control specific tiny populations of neurons very precisely, cause them to eat a ton, to stop eating, to gain fat, to lose fat, like the animals are marionettes. I mean, that's the level of understanding we have right now of how these systems work. So, I mean, all of this evidence is converging on the same thing, that the brain is central and that fat cell metabolism, I'm just

not seeing the evidence for that. I mean, Gary, if you want to cite specific evidence demonstrating that that is an actual cause of differences in body fatness between individuals in the general population, I'm awaiting that evidence. And I'm happy to sit here and listen to you cite the evidence that demonstrates that. Can I pause here? Yeah. Leptin is produced where? Yeah. Leptin is produced.

Yeah. Let's talk about leptin a little bit. It's produced in fat cells. And it's produced in proportion to the size of fat tissue. So the amount of body fat you have, the more fat you have, the more leptin you have in the circulation. And basically what this is, it's what's called the negative feedback loop, which is a really simple engineering term that works like a thermostat. So with your thermostat, if you set your thermostat to 70, if it starts getting a

little bit hotter, your AC turns on to bring it back down. If it starts getting lower, the heat comes on to bring it up. That's called the negative feedback system, and it maintains the stability of the temperature of your house. We have many negative feedback loops in the human body to regulate body temperature, to regulate blood pressure, to regulate all sorts of things. One of the negative feedback loops we have regulates body fatness. And the hormone, so your thermostat measures temperature

by using a thermostat, sorry, a thermometer. Your brain measures body fatness using this hormone leptin that's in the circulation and then particularly when your body fat level drops your leptin levels drop and your brain hears that and it kicks in a starvation response basically and this is the main reason why weight loss is so difficult because your brain is like no i don't want to be losing fat and it makes you hungrier it increases your cravings yeah is that at a certain level of body fat is this um so here's just when you're losing body fat in general like even if you're a large person that's overweight

correct when you're losing body fat in general your body exacerbates your hunger and this is this is the thing that's really important to understand about obesity is that people with obesity have a higher set point. So it's like turning your thermostat from 70 to 80 and then your thermostat's regulating around 80. People with obesity, they're not regulating around 170 anymore. They're regulating around 250. And so when you cause a lean person to lose weight, you see the same thing as when you cause a person with obesity to lose weight. You see this reaction in their brain circuits that regulate body fatness that drives them to increase their cravings and their hunger, metabolic rate drops. So it would be an evolutionary mechanism to force you to seek food.

Correct. And not just to force you to seek food. That's the main thing, but it also slows your metabolic rate does everything it can to get more energy in your body and have less leaving and it keeps doing that until the fat comes back can i pause here yeah so when you're eating a sugary diet a high high calorie diet you will produce more fat your body will get fatter right it depends on how many calories you're eating. Okay. If you're overeating, you're consuming a lot of sugar, a lot of carbohydrates, your body will get fatter. Correct. So your body will produce more leptin.

Correct. So it comes from the diet. Yeah, indirectly, definitely. Can I pause? Please. So the leptin is produced not just in response to the size of the fat cell, but in response actually to glucose-mediated uptake into the fat cell, which is mediated in part by insulin. So you come back to insulin, even with the leptin, you raise blood sugar, and that's

the carbs. You eat the carbs, you raise blood sugar, you raise insulin, you raise fat storage, the glucose, and then you get more leptin. Again, one of the things you have to understand about this is everything that's said has two interpretations depending on which paradigm you're looking at, and these are fundamentally different paradigms. So in Stefan's world, and again, correct me if I'm wrong, though, leptin is signaling fuel availability in the fat cells the way I would think of it in my very small world, leptin is responding to fuel availability in the rest of the cells.

So it's basically a molecule that can tell other cells that there's fat available, and you could burn that fat for fuel, and then you don't have to go eat. Or it can tell that there isn't fuel available. And depending on how much leptin there is, the cells, and then that will respond by a signal to eat or not, to disinhibit eating behavior. Everything we're talking about, Stefan and I first sort of fell out, I don't know, eight years ago at Ancestral Health Symposium when I acted improperly, inappropriately. But one of the problems I had, so the way I think you should think about this, you have a hypothesis, and this is a fundamental thing, is obesity caused by overeating. Because we know if you're getting fatter, you're storing more calories than you expend.

That's just, you know, that just like if a room is getting more crowded more people are entering than leaving. That is the simplest but it doesn't tell you why the room is getting crowded it doesn't tell you why you're getting fatter. And again what I've been arguing is the why you're getting fatter part has been left out and people decided that overeating was somehow an explanation

and then they went to the brain to look at why people might overeat. So one of the questions I asked Stefan eight years ago, and it keeps coming up, is if we're going to blame obesity on the modern food environment, epidemics of obesity. You know, a simple question to ask is, can we find epidemics of obesity without this modern food environment? I mean, that's this sort of science 101, right? And it turns out that the world is full. And the first one I found in the literature was in 1902 in a population of the Pima, Native American tribe of the Pima living in Arizona. And observers saying these people are poor, they're malnourished, they're suffering through famines.

They've been suffering through a famine for 40 years, and famines, it's hard to overeat during a famine. And yet the women of the tribe who do virtually all the work, they were treated as pack animals in effect, were obese. So now we can disassociate obesity from the modern food environment, and we could disassociate it from this ultra-processed foods we eat and start to ask the question, what is it about? Can we find what might have driven obesity in that population, despite the existence of famine? So it's from very simple observation. Once we get into these kind of studies, say this, and human genome studies say that, I actually rarely do that in my books, because you can find studies that will say anything. And you'll see in the studies people misinterpreting them. What was the cause of the population of women to be obese?

Well, so one of the things that happened during the beginning in the 1860s, the Pima were put on a – well, they moved on to – they were reservationized, whatever the verb form would be. And they began eating Western foods. And back then it was sugar, flour, and lard for the most part and sugary beverages probably. So that's a reasonable hypothesis. And you could find the same thing in the Sioux, Native American Sioux population living on a reservation in 1928 where you had both obese men and women living with malnourished, stunted children who clearly weren't getting enough diet, but they were on a reservation. They were getting Western foods. So ultimately, you know, the question you ask in science determines the answer you get. So the question I was asking is we have this observation that any population that transitions to Western diet or Western diet and lifestyle gets obese and diabetic.

They develop what's called metabolic syndrome, which is insulin resistance and all these issues. And we know that's true all over the world, from the Inuit to the Pima to South Pacific Islanders to Africans to Europeans. So the genetics aren't that important. The question is, what's triggering it in the environment? And again, Stephan would say, well, there's too much food available, and it's too palatable, and we can't say no. And I have a lot of problems with the we can't say no part, because if we're lean, it means they can't say no, and they being the people with obesity, and I don't believe that's true. And then, or is it some specific item or some specific group in these foods that travel with Western populations? And so the ability, and today if you look up dual burden of obesity and malnutrition,

I have a Dropbox folder I could share with you. There's probably 50 studies all over the world. You see the same observation. Incredibly poor populations, malnourished. The children are stunted, which means they're protein deficient and they're calorie deficient. And often the mothers or the aunts are obese. The obesity tends to run in the females, which suggests it has a female sex hormone related effect that I don't believe works in the brain because we're dealing with populations that could not have overeaten. If they could have overeaten, why are

the kids starving? That's sort of the question. And this was the first thing that I think we fought about back then. And it's still, if you can find populations with obesity epidemics, You can find populations with obesity epidemics, but without the modern food system, without snack wells and without Lay's potato chips. And if you know that they're going through a famine or you know that the kids at least aren't getting enough food, how do you explain obesity in the mothers without assuming that the mothers are overeating. Let's pause right there. Stephan, is there a population of people that are obese, that are not eating a Western diet, that are not eating sugary foods? That are obese and that are not eating sugary foods? Probably not because generally once you have an industrialized food system,

that's going to include sugar but there are populations that eat a lot of sugar and are not obese and we should talk about some of these actually let's let's talk about can you go back to the yeah sure let's talk about the pima first um now gary has told a story he's told his version of the Pima story. Let me tell the story, the version of the story that appears in the scientific literature. Now, the Pima, originally, they were agriculturalists. They were eating, traditionally, a very high-carbohydrate diet based on unrefined carbohydrates. Originally, it was corn, beans, and squash, primarily. They were hunter-gatherers and agriculturalists.

They were hunters. Gary, okay. They were primarily eating agricultural foods. They were also collecting some wild foods. That's correct. They were fishing and eating mesquite pods, primarily agricultural. And data are very clear on that, Gary. No, no, no. Yes, they are.

Look, we have data. We can't say things like that, stephan because we're going to disagree on what the data let's let's move on you think they mostly fish that's incorrect okay according to the data that's i remember you saying that in your book something to that effect stephan read what you've got my book read what i say anyway just read what i say let's go on we don't have to argue about it. Read what I say. I'm going to move on here. Now, the Pima traditionally were agriculturalists. And what happened basically is you had all these farmers moving into their area, settlers of European descent, and they diverted the water from their river, the Gila or Gila River, if you can pronounce it. Gila. the Gila or Gila river, if you pronounce Gila. And so they were no longer able to grow their crops, their agricultural crops that they were primarily dependent on. And therefore the government started providing them with foods to eat. And these were calorie dense, refined foods.

They were like Gary said, uh, flour, lard and sugar. And then they became very obese now there was a population of pima right across the border from them in mexico also very similar culturally and all that that maintained their traditional high carbohydrate lifestyle and agricultural lifestyle and there have been studies comparing those two populations and the ones across the border with their traditional lifestyle are a lot leaner and healthier, not surprisingly, than the ones eating lard, flour, and sugar, okay? But Gary, you seem to believe that people can gain weight. You kept referring to famines and things.

You seem to believe that people can gain weight even if they are eating very few calories, and you refer to this many times in your writing. eating very few calories. And you refer to this many times in your writing. And, you know, these are very casual observations that you're making kind of these casual correlations and storytelling. But if you actually look at the data on this, what you see is that if you just measure calorie intake in people who have obesity. It is 20% to 35% higher than people who are lean. Okay. After correcting for height, physical activity level. And I've got the references there.

Can I? No. It's okay. We're getting a little bit into the weeds here. Let me give you an example. Reference number seven. Can I pause you guys right here? So these people, they have essentially the same lineage.

One group lives in Mexico. They're not eating these sugary foods in this Western diet. The ones that live in America are. The ones that live in America are becoming obese. The ones that live in Mexico are not. Is that correct? Correct, yeah. And so now if you have someone with obesity, like I've said, the most accurate measures that we have

suggest that they habitually consume and expend more calories. And now Gary's model says that that is downstream of the fattening effect. It's not causing the fattening effect. It is a result of the fattening effect. Whereas my model says that that is actually required for the fattening effect to occur. It is upstream. Now, what happens, Gary? What happens if you reduce their calorie intake by that same amount, 20% to 35%?

It doesn't matter if you do it by restricting carbs or fat. These experiments have been done. They lose weight when you restrict their calorie intake down to that of a lean person. So this is the argument, what you're saying, that consuming low amounts of calories but high amounts of sugar doesn't make sense, you can get obese that way. Right. So you're saying it's a calorie- Yeah, correct. And that's reference number nine and 10 to support what I just said.

And I want to talk about another one that really- Wait, wait, can we hold on, Stephan? Yeah, yeah, let's keep going. to support what I just said. And I want to talk about another one that really... Can we hold on, Stephen? You didn't... The reason I was using the dual burden example is because we have to explain how those women were eating all those calories. Usually women, again, it's just... Often these studies were done by diabetes researchers who were studying diabetes in these populations,

and the men had high levels of diabetes and the women had high levels of obesity. To give you an example where that measurement was done, in Trinidad in the 1960s, and again, all I'm doing, this is the role I played, is I asked the question, can you find populations that don't have a lot of food? Okay, you could say that the obese expend a lot of energy and they eat a lot of calories.

The question is, can they get obese without a lot of food? And so can we find populations? Like you asked, can you find a population that gets obese without sugar, which was exactly the question to ask. So in Trinidad in the 1960s, there's a malnutrition crisis. The U.S. government sends a team of researchers down to study this. And the researchers come back and say, yeah, there's malnutrition, there's stunting, there's deficiency diseases, and two-thirds of the adult women are obese. And this is a medical problem. And the next year, an MIT nutritionist goes down to do exactly what Stephan asks for, and to actually measure the diets in obese women and lean women, and to study it. And this is a

population where it's not like, I mean, this is a very poor Trinidad population, and reports that they, I think it was 1,800 calories a day, what the obese women were eating was actually a little less than what the lean people seemed to be eating, and that it was lower than what the Food and Agriculture Organization considered for a healthy diet. So again, what my role in this is to point out when you have populations like that, I don't see how the overeating hypothesis tells me the brain is in control of how much they eat, tells me anything about why the women were obese, especially when their kids are starving. This is the paradox of the stool burden, an obese mother with a starving child. If the obese mother has to eat superfluous calories to get fat, why isn't she giving those calories to her kids?

Because she doesn't need them. She clearly doesn't need them. She's got fuel. So what's going on there? If you posit a hypothesis, as I did, which says that the obesity is triggered by the macronutrient content of the diet, then you can explain. I mean, there are plenty of animal models. A famous quote I use in my books from Jean Maillard, it was like the famed leading Harvard nutritionist who studied an obese strain of animals in the 50s. He said, my animals will get

fat even when half-starved. They will make fat out of their food even when half-starved. These are generally animals with mutations in the leptin pathway, by the way. It doesn't. Whatever gene it is. Whatever gene it is. The question is if I can make fat out of my food at levels of – at caloric levels that, for instance, a lean person can't, then I'm going to get fat eating the same amount. since a lean person can't, then I'm going to get fat eating the same amount. And that fat accumulation is going to be, you know, means I'm taking in more calories than I expend. But the

point is, I'm for some metabolic hormonal reason, I'm taking the fuel I eat and turning it into fat and storing it in the fat tissue. What is your response to this? Yeah, so my response is that if you want the best answers, you have to use the best methods to answer the questions, okay? If you want a question answered properly, you have to use accurate methods to answer that question. Now, as you know, Gary, it's very difficult to measure food intake in free-living individuals, particularly you're traveling to a country you've never been to before. It's very difficult to get accurate measures. So just because some guy went to Trinidad and claimed... It was a woman, actually.

Okay, fine. Just because some woman went to Trinidad and claimed that people were eating 1,800 calories and becoming obese does not mean that that's what actually happened. Now, let me... No, no, no, no, no. Gary, I'm responding. No, no, no, no, Gary, I'm responding. Now, we have studies where researchers used accurate measures to measure calorie intake in people who had obesity. Many of these people were saying were only eating 1200 calories a day. When they actually measured their calorie intake, what they found was that they were consistently eating more calories than lean people. So this phenomenon that Gary describes is something that is only observed when inferior methods are used to measure calorie intake.

Wait, Stefan, the reason I'm using these populations, like I said, I'm just giving you an observation. Obese mother with a starving child, the dual burden of malnutrition and obesity. This isn't one observation. It's not one nutritionist. The existence of the starving children strongly suggests that there's not a lot of food available. And we have to explain obesity in the mother. That's what I would like you to respond to. Okay, fine. I will respond to that. Now, look, I haven't looked at these studies in particular. I brought them up eight years ago. We got in a fight about it. We fell out eight years ago. It ruined our, you know, it's like we used to be buddies.

So now, look, there are many reasons why a child could be malnourished in a non-industrial situation. And this is, I do a lot of work related to this. in a non-industrial situation. And this is, I do a lot of work related to this. What you see in non-industrial situations, you see a lot of infectious disease. You see a lot of malnutrition. So people not getting enough essential minerals and vitamins,

not getting enough protein. And you see a lot of children who are just barely hanging on because of this collection of really bad stuff that's happening in their lives. And so- Parasites, things along those lines. Yeah, yeah. Parasites, malaria. I don't know if there's malaria in Trinidad or not, but I mean, all the diarrhea, pneumonia, these are the things that we all had before we had modern medicine and great sanitation in a country like the United States. 30% of kids didn't even make it past childhood. And so there's a lot of things that

could have caused that, Gary. It's not necessarily because, you know, it's not necessarily the reason that you attribute it to. Now... I'm not attributing it to a reason. I'm just asking for explanations. Well, great. Well, I don't have the explanation, but I'm throwing out possibilities that are alternative to the one that you're implying. And that's quite possible. Okay. So, again, when you use accurate measures of calorie intake, you find that these people with magical metabolisms who have obesity and don't eat very much seem to not exist anymore. exist anymore. And furthermore, I want to get to another type of study that's really going to differentiate between this metabolic effect driven by insulin and the effect of calories.

So we have a lot of studies that compared diets in which calories were the same, but carbohydrate and fat intake differed. And the ones that I really want to focus on right now that I think are key here are the studies where they increased calorie intake. So they fed people. One study in particular, and let's see, I'm going to give you a number here. Let me see if I can give you a number here. Sorry. While you look at that, can we bring up another issue? Because what we're talking about ultimately is why people get fat. Okay. I don't want to divert here. I'm in the middle of something.

So now if we want to understand why people get fat, we can look at studies that overfed people on fat or carbohydrate exclusively. studies that overfed people on fat or carbohydrate exclusively. So this one study, the first one that I want to talk about, first they figured out people's baseline calorie intake, figured out how many calories they needed just to maintain, and then they increased that by 50% by exclusively giving them fat or exclusively giving them carbohydrate. Which study was this? This is Horton.

Okay. Give me a second when you're done. Yeah, so number 16. Number 16. So now if Gary's hypothesis is correct, these people should have gained body fat on the carbohydrate overfeeding but not the fat overfeeding because that increases your insulin and has these effects on your fat cells, et cetera. Okay very rigorous studies i want to emphasize that can i pause here did they

monitor the the actual calories they got correct yes they were they were good they had a baseline they used prisoners in the vermont state prison no that's incorrect this is a different study so they had a baseline and did they require them to maintain the same diet And then add additional fat or additional carbohydrates? Yes So same diet And then they just bump it up with fat Or bump it up with carbohydrate

Which study did Horton do? It wasn't Sims, it was Ethan Sims Which study did he do that was not prisoners? What was the He didn't have a metabolic war You know what, let me just finish describing this study. Gary, that's an irrelevant detail, okay? What's relevant is that you just implied that I don't know what I'm talking about.

Gary, you know what, I don't actually know. Maybe it was in prisoners, okay? Thank you. All right, you're welcome. Now, but it was not the Sims overfeeding study that was done in prisoners. That's what I know. Okay. Okay.

The reference, what's the reference? Yeah, it's on my website. You can go to my website, stephangeana.com, and it's reference number 16, and they're both there. Okay. So this was what's called a metabolic ward study where these people were in a research facility where the researchers could monitor and control every morsel of food. So there was no cheating, no inaccuracy, and they were measuring changes in body fatness using a gold standard method called underwater weighing. Okay. And so what they found was that at the end of a two week period of overfeeding, the carb and the fat groups gained the exact same amount

of body fat, exact same amount of body fat. There was another second study that did the same thing and found the same result. Independent lab group, very similar experiment, three-week long instead of two weeks, they found the exact same thing, same amount of fat gain, different insulin responses, different amounts of carbohydrate and fat, exact same amount of fat gain. So this demonstrates that insulin and carbs are not what controls what gets fat into fat tissue. Calorie intake is what controls that. So let me explain again. Remember I talked about the paradigm you work in determines the question you ask.

And this experiment is a classic example because they assume that people get fat by overfeeding. So then they say, if we overfeed them, we're just doing what happens naturally. Everything about the experiment is based on the assumption that they're supposed to be testing, which is can people get fat by overfeeding. And so from the very conception of the experiment, they've built in the paradigm that we want to test, the hypothesis. On top of it, if it's a typical Sims experiment, I actually wasn't familiar with this one.

Oh, it wasn't Sims. It was James Hill and J.C. Peters. James Hill was funded from about 1998 to about 2008 by Procter & Gamble because he was an Alestra shill. I hate to say that, Jim. I apologize, but I think it's a fair assessment. And then when he stopped being funded by Procter & Gamble, he was funded by the sugar industry. And J.C. Peters was the head of the Procter & Gamble Alestra. Alestra, which is now something that no one eats.

Yeah, Alestra was a fat substitute. The problem was you got, like, run out. Ruthless diarrhea. Yeah, and shit like that. But the whole idea of Alestra was to replace fat in the diet. So every study Hill and Peters did implicated dietary fat as a cause of obesity. I don't think we could ever use – I hate to say it. Typically, I don't think funding influences results, but I wouldn't use a James Hill study to make that point.

Because you think it's a biased study that was influenced by it? Everything Hill and Peters did. I mean, I talked about this in Good Calories, Bad Calories. When they reported their results, actually, I did a FOIA on James Hill because he works for the University of Colorado. So you could actually, again, I got all his documents back and forth between him and Alestra. I'd be happy to share them with you if you'd like. They're revelatory. I mean, him and Procter & Gamble.

But he basically held Procter & Gamble for ransom. He would get a $500,000 unrestricted gift, and then he would do a study, and then he would ask, and would conclude that fat is bad and carbs are good, and therefore Elestra is a viable product. Then he would ask for Procter & Gamble for more money before he then published the study. So it's a particularly egregious example of someone who's, I suspect it was just his belief system. He believed dietary fat was bad, fat caused obesity. Lester is a good thing because you eat that instead of fat,

you don't absorb it. And then every study he did confirmed that. The point that we keep getting away from that I haven't had an opportunity to and Stefan knows this as well as I do if you're gaining say four pounds a year of fat or let's say between 20 and 40 you've put on 40 extra pounds so now you're obese you're a nice lean healthy young guy in 20 like many of us were and by the time you're 40, you've got 40 pounds of excess fat. That's the equivalent of putting in about 10 calories a day, storing about 10 calories a day into your fat tissue that you don't burn or metabolize. So you eat, say,

2,700 calories a day, half carbs, 35% fat, 15% protein, and 10 calories a day get trapped in your fat tissue. Less than a bite's worth of food, less than a sip's worth of beer. So the question we're actually trying to ask is, or answer, and this is, again, just my approach as a curious journalist with a science background, is how do we explain those 10 calories? Because when we talk about those obese women with starving children, all those obese women were doing was storing 10 or 20 calories a day, depending on how quickly they became obese in those populations that tends to happen quickly in their 20s. So we're asking this question, how do we – you've got a situation where we have to end up with 10 calories stuck in the fat cells every day. That's 20, 30, 40 billion fat cells, so it's divided up very

small. And is the brain somehow regulating that? Or again, is there a dysregulation in the body involving pick your hormones, pick your enzymes that somehow traps fat in the fat cells or prevents the fat from being used for fuel when it's released from the fat cells? And so if you think about it that way, like you let yourself go to seed. Today, Joe Rogan decides, I'm done. I'm going to do nothing but drink beer. And you might start go to seed. Today, Joe Rogan decides, I'm done. I'm going to do nothing but drink beer. And you might start drinking five beers a day. And over the course of 10 years, you get 20 pounds and it's all here. That 20 pounds over the course of 10 years is still only about 20 calories. You might have added 800 calories of beer to your diet and stored 20 calories as fat. How does that happen? And why does it go here

and not elsewhere? And as Stefan said, this is insulin-dependent fat tissue. So when we're talking about this, like this question, can somebody get fat during a famine? Or can they stay fat during a famine? All they have to do is hold on to 10 calories a day extra. If they're only eating 1,200, 10 get stuck in their fat cells, 1,190 is excreted or expended. It's not that hard to imagine. And there's nothing in the laws of physics that says it. So what could be dysregulated about their fat cells even during a relative famine, not a complete famine, but a relative famine that might be? And again, animal experiments of which there are probably hundreds by now, different animal models, you can disassociate obesity from eating too much in the animals.

Can I pause you for a second? Yeah. So essentially you're saying that even if someone is taking in a good amount of calories a smart amount of calories 2 000 calories a day if you're taking in these calories in the form of sugar your body is going to take a certain percentage of them even if you're getting enough food and store it as fat. Whereas if you were taking in just protein and vegetables and things along those lines, your body would not do that. Well, so this gets to the mechanism question and the evidence question. But you're saying that, right?

So you're saying that if two people are on the same diet, one of them is on 2,000 calories of chicken and fish and vegetables, and the other one is on 2 2 000 calories of chicken and fish and vegetables and the other one is on 2 000 calories of milkshakes and you know sugary drinks and pasta and bullshit that that person is going to gain a certain amount of calories and just put them to fat right regardless that's yeah that's the same activity this being a science, that hypothesis can be tested. Yes. And Stefan thinks it's been tested 80 times, a dozen times. I think they've done a bad job of testing it, and we will both tend to reject the studies that we don't like when we define don't like by whether or not they got the answer we think is correct.

Your perspective is that this is not the case your perspective is that like as you were saying in the study where they closely monitored these people's diets and they added additional fat and additional carbohydrates that they both gain the same additional amount of weight that's right i mean if kerry's hypothesis is correct you have to see different levels of fat gain i mean gary's a short term study yeah it was how short term was it uh two and three weeks well that's very short yeah Is correct. You have to see different levels of fat gain. Was this a short-term study that they did? Yeah, it was short-term. How short-term was it? Two and three weeks.

Well, that's very short-term. Yeah, it is very short-term. But still, Gary says that insulin is the thing that gets fat in fat cells. I mean, you would see some kind of difference. If insulin made any difference, you should have seen some kind of effect, right? Some kind of difference in fat gain. Well, actually, I don't want to start taking out charts, but this gets into insulin dynamics that was worked out.

So over a – I promised I wasn't going to say oy. Oy? Oy on the show, but it's my – thanks to my Brooklyn-born mother, it's my program, Dan. And the same is true. A lot of these overfeeding experiments do the same thing. So when they talk about overfeeding, they literally overfeed. So they kind of do a reasonable way of figuring out what you're eating.

As Stefan said, they calculated how much energy they needed to stay in energy imbalance. And again, right there, that's a problem. Because one of the hypotheses says that energy balance is dependent on the macronutrient content of the food. So you're going to get a different level depending on what the macronutrient content is. And then- A different level of? Of what's necessary for energy balance.

Okay. So the classic example is a study that's my not-for-profit funded that's been very controversial, where they got their subjects, this is David Ludwig and Cara Ebeling and their colleagues at Harvard and Boston Children's Hospital. And they did this study in Framingham. And they basically got subjects to lose 10 or 12 percent of their body weight. And then they randomized them to three different diets of three different macronutrient compositions. And they basically calculated their energy expenditure on the three

different diets, which is kind of exactly what we're talking about, because if you want to be in energy balance, you know you feed people exactly what they're expending. And in that study, which was published a year ago, they saw different levels of energy expenditure depending on the carbohydrate content of the diet. So the higher level of carbohydrates, this is trying to keep them in energy balance. The higher the carbohydrate, the lower the energy expenditure. The lower the carbohydrate, the higher the energy expenditure. So again, it's just whether or not they did the study right. Who knows? Science is a compilation of a lot of studies, and we're trying to address exactly this point. But merely building that into the experiment, we know what their

energy expenditure should be. And then the point is when you increase, and again, part of the trick of doing science is to say, look, we have competing hypotheses, multiple hypotheses. And it's vitally important that you always keep the multiple hypotheses in mind when you're interpreting the study. So one hypothesis says it's how much they eat, and another hypothesis says it's what they eat, and that what they eat is moderated primarily through insulin. And when you do these experiments, like the experiment that Stephen is talking about, Stefan, now I'm completely confused. If you overfeed them, you start out with a 50% carb diet, now you overfeed them. If there's a threshold effect on insulin, which it turns out there is, then you're just

moving them. And when you look at insulin dynamics, when insulin is below a very low point, the fat cells will mobilize fat and the lean tissue will burn it for fuel. And above that point, you get pretty much flat. So if you start people who are eating 1,500 calories from carbs and you add them, bump them up to 2,500 calories from carbs, you're still in the plateau side of the insulin. You wouldn't necessarily expect to see any difference. The only way you expect to see a difference, and this is why it helps to really interrogate both hypotheses so that you know when you're doing the experiment whether or not you're actually testing something. You want to set up the experiment so the hypothesis predicts,

the two hypotheses predict something entirely different. This experiment, arguably the two hypotheses predict the same thing. You'll get fat gain because insulin is elevated regardless. And when insulin is elevated, you're going to get fat gain. The question comes back to this again, always vital to keep this in mind. What could possibly cause a 10 or 20 calorie excess that causes fat storage? I have a friend that was 400 pounds when he was 18. He was a tall kid, about six foot five. He was, say, 200 pounds overweight. 200 pounds overweight is roughly 100 excess calories over 18 years

stored in your fat cells. That's, you know, even if you assume that you have to consume 300 calories to have 100 excess stored in your fat cells, that's, you know, two Coca-Colas a day that he was drinking or one half a quarter pounder a day that he was eating that his lean friends weren't. And the question would be, why can't he just stop doing that? And again, Stephan would say, because his brain won't let him. And I would say, because his insulin is elevated, it doesn't matter whether he stops it or not. Can I respond here?

He's got to address the underlying mechanism. Okay. All right. So now, again, it's easy to tell stories. It's not easy to tell stories that are supported by scientific evidence. Now, I want to bring people's attention to reference number 11 on my site. There have been 29 studies now that have measured differences in energy expenditure, metabolic rate. Is this the Kevin Hall study?

Meta-analysis, correct. There have been 29 studies to date that have measured calorie expenditure, metabolic rate on diets differing in carbohydrate and fat content. And when you put all those studies together, or at least the first 28 together, and you look at what the overall literature says, it makes almost no difference to metabolic rate whether people are eating carbohydrate or fat. And in fact, this very small difference that it does make actually favors high-carbohydrate diets.

So you get a slightly higher metabolic rate when the diet is predominantly carbohydrate now this study that gary cited is the one study out of these 29 that has reported a larger effect than any others of carbohydrate restriction on energy expenditure so this study reported an effect bigger than any of these other 28. And the difference, we would say, is this. Gary, I'm not done. Gary, please. Thank you.

And interestingly, if you actually look at the data, and these data have been reanalyzed by a researcher named Kevin Hall, and if you look at the data, you find that some of the participants, some of the data that represent some of these participants are literally physically impossible. They break the first law of thermodynamics. This is a conservation of energy. Gary knows about this. He has a physics background. And they literally don't add up. And when you start subtracting the clearly erroneous data from the pool of subjects, this big effect size starts to shrink and shrink and shrink and shrink until after you've gotten rid of all of it,

this study no longer reports a higher energy expenditure on a very low-carbohydrate diet, and it's consistent with the previous 28 studies that were done. So that's my perspective on that. But I want to go back to this energy. No, no, no, Gary, you talked for a long time, and I'm going to talk for as long as I want now. I want to talk about human energy metabolism

and this idea of the 10 extra calories a day. Gary, I really continue to get the feeling that you do not understand human energetics because that's not how it works. Well, no, I'm just saying 10 calories stored in a fat tissue. That's just mathematics. 10 calories. I didn't say anything about how much you have to eat.

I'm not done. Okay, no, but you're insulting me, Stephen. You've got to stop doing that, dude. You keep acting like you think I'm an idiot. All right, are you done now? Are you done? Can we be clear that we're talking about... Are you done now? Can I just finish this? No clear that we're talking about – Are you done now?

Can I just finish this? No, you can't until I am done. You can't attack me without – Gary, you have time to respond. You can respond. Write down notes on what you want to respond to, and after he's done, you can talk about it. Yeah, but we're going to get into a long discourse on something that's not the point. Well, let's find out if it is the point.

We don't know what he's going to say. Thank you. Okay. Now, what you see – there's basically two things you need to pay attention to here in terms of energetics. One is the imbalance between intake and expenditure, and that is very small. So it only takes a little bit of extra calories to cause somebody to start gaining fat. However, as they gain fat, their bodies get bigger. They're gaining fat and lean mass. People with obesity have more fat, more lean mass, and their calorie needs go up and up and up and up the larger their bodies get. And so even though the imbalance between energy intake and expenditure is small, their calorie needs end up being quite a bit higher. Can I pause for a second? Yeah. So you're saying that someone just gaining calories, eating additional calories,

their body gains lean mass as well? Yeah, that's correct. How does the brain regulate that? I didn't say it regulated that. Gary, Gary, Gary, hold on. That's fascinating. How does the brain do that? Muscle?

They're gaining muscle tissue? Some of it's muscle, some of it's liver and organs. Okay. Is this because they're carrying around this extra weight and so the extra calories and then on top of that carrying around the extra weight forces their body to grow larger? Presumably. I'm actually not sure what the mechanism is. But it doesn't have anything to do with the brain? It's just a coincidence? I don't know what it causes it. That's what I'm saying, Gary. Okay. Now, so, but the point is, by the time the person has obesity, they are consuming 20 to 35% more calories than they were when they were lean.

So, it's not just one or two Cokes a day that is allowing them to remain obese. They are consuming 20 to 35% more calories. of one or two Cokes a day that is allowing them to remain obese. They are consuming 20% to 35% more calories. That is what the most accurate studies are saying. And so it's not just 10 extra calories or maybe just one or two Cokes. We're talking about a substantial amount of extra calories. But isn't this a generalization? Because we don't know. I mean, what's the ratio of how much weight people are gaining?

Everybody gains a different amount of weight. Like when you're saying they're eating 20% to 30% more calories, like who is? Like how much are they gaining? Like people get fat, they get 20 pounds overweight. People get fat, they get 100 pounds overweight. I mean, it varies widely. Yeah, and that's why I give a range because what you see is that people who are overweight, so they're in the overweight range and just have some extra fat,

they eat about 10% extra calories. People who have a little bit of obesity eat about 20% extra calories. People who have very, very great obesity eat more like 35%. So it tracks with the amount. I'm sorry. Is it possible what he was saying, that if you do consume 10 extra calories over long periods of time, that will accumulate? No, it's not 10 extra calories. You're accumulating 10 extra calories.

It's like a dime is going into the bank. How much do you have to deposit to get the dime? It is correct that if every day you eat 10 calories more than what you need, then yes. Or your body stores. Or your body stores. Yeah, we'll say that. That's correct. If your body is storing 10 extra calories over top of what you need.

But the thing is that as you get bigger, what you need goes up and up and up. Because you're carrying around more weight. Correct. And so it's 10 extra calories on top of the elevated amount that you're already eating. So you end up with these big differences in calorie intake. So that's how it really works. But I want to talk about some interesting observations because, Gary, you like to talk about, you know, what's going on in different dietary trends and different cultures. And I find that pretty interesting, too. I want to talk about the fact that sugar intake in the

United States has been declining for the last 20 years. So it peaked in 1999. And it is currently depending on which source of evidence you believe 15 to 23% lower than it was in 1999. This has been corroborated by a number of different sources of evidence. This is number 17 on my blog. And, of course, we know that obesity has increased, diabetes has increased substantially over the last 20 years in the U.S. The percentage of the population or actual numbers? Correct. Percentage, yeah.

And in the U.K., sugar intake has been declining for 50 years. I don't believe that. Okay. Well, you can argue with the data. They're number 17 on my blog. They're about 22% lower. And this is what we see across a number of different industrialized countries. You see a stagnation or decline in sugar intake in recent decades as obesity rates are continuing to increase and of course that 50-year period that covers the decline in the uk covers the entire uk obesity and diabetes epidemics um but there's another one i want to talk about that can i respond to that yeah we should probably respond to that

stephan actually i'll let you respond for me because we had this debate with the Cato Foundation. So you know my counterargument. Do you want to give it? Yeah, sure. Absolutely. I mean, are you sure you want to let me give it, though? I might correct it. Okay.

All right. that the amount of sugar that we consumed 20 years ago, or even maybe 50 years ago, may be continuing to fatten us today. And it's about the sugar that we used to eat 20 or 50 years ago, and not necessarily about the sugar we eat today. Well, it's not exactly right. Okay. So the argument I made was, because he brought this up when we had to do a written debate on the Cato Foundation website. And it's interesting, if you think about, use tobacco as an example. So tobacco smoking, per capita smoking in America peaked in 1965 right after the Surgeon General's report. And it took 30 years before lung cancer rates turned over.

Okay, and I think we both agree that cigarettes are a major cause of lung cancer, smoking. So what you basically have is a system in which if there are any, there's the assumption that Stefan is making when he quotes this kind of data is that the relationship between sugar and obesity is linear. So as sugar goes up, obesity and diabetes goes up, and if sugar turns over, they don't. So here's the thought experiment I used in Cato, which is 1965, we're smoking per capita about 20 cigarettes a day.

As it starts to come down, imagine we only cut that to 17 cigarettes or 16 cigarettes, a 20% reduction in smoking. Would you expect to see a reduction in the lung cancer rates? Again, this is the point I made about what you would expect to see rather than using simplistic metaphors. So the question is, would you, like Joe, we go from 20 to 16, do you expect to see the lung cancer rates turn over? No. No. And in sugar, we went from-

Probably see them drop. No, you might, the derivative might drop you might expect it to slow a tiny bit still you it's there's a it's a weird comparison because one of them is poison the other one's food right well but in this case the food the question is how toxic is the food so in sugar we have a variety in, what happened is the equivalent of going from 20 cigarettes to 16 beginning in 1999. And Stefan is saying, I would expect to see an immediate change in obesity. And in fact, if you actually look at the rates, the rate of increase, the prevalence appeared to plateau around six or seven years later. Who knows whether that's relevant.

later. Who knows whether that's relevant? But to get a small decrease in sugar, even if it's 20%, that's 20 to 16 cigarettes. And the other factor that I talk about in my book, and Stefan knows this, is you very clearly have maternal transmission of the propensity to obesity and diabetes. So there's a generational effect. And this is studies that were done on the same Pima, the same Native American tribe, where each generation gets more and more susceptible to whatever it is in the diet that's triggering an obesity and diabetes. So if that's been happening in the United States and around the world, you've got a generational effect that could last far longer, might even keep going indefinitely, even if the sugar levels drop. So you have the sugar quick kicking off the obesity epidemic. And yes,

Stefan's about to say this is a story, and it is a story. But it's clearly the case that mothers who are obese during pregnancy or diabetic or gestationally diabetic, they become diabetic during pregnancy, or they have metabolic syndrome. They're just insulin resistant or they gain a lot of weight in pregnancy will give birth to children who are at higher risk of becoming an obese and diabetic when they get older and at younger ages. And those children will pass it on. So, again, we have, you know, it would be nice, I would love it if sugar consumption came down, and with it, obesity and diabetes plummeted. But it's not in any way a refutation of this hypothesis, which I just want to state what it is, because people get confused about it, and we never got to it.

The sugar hypothesis is a little different than what we've been talking about. And it's pretty simple. We have obesity and diabetes epidemics worldwide, as we talked about. It doesn't matter the genetics of the population. You add something about a Western diet to those populations, Western diet and lifestyle, you get these explosions of epidemics of obesity and diabetes. And what I'm hypothesizing in this book is that sugar is something that has to be added.

Maybe it's sugary beverages, for all I know. Or it could be a more complex hypothesis. The single possible one is you add sugar to any population's diet and sufficient, whether it's Southeast Asians living on rice or the Inuit living on reindeer and whatever, or the Native Americans of the Great Plains or, you know, Caucasians living in the Upper East Side of Manhattan, add enough sugar. And eventually, through the metabolic effects of the sugar and the generational effects, you will get explosions of obesity and diabetes and metabolic syndrome. Stephen, you want to respond to that? Sure. I mean, Gary, you called it, man. It's always possible to tell a story to salvage your hypothesis, but that doesn't necessarily make the story correct.

I mean, I can come up with a story that cosmic rays cause obesity by hitting my fat cells and making them fat you can't disprove that nobody here can disprove that but no no we could do an experiment to protect you from okay sure but we don't have we don't have the data right now you don't have data supporting your hypothesis no we do you just dismissed no no no no well can i get back to the kevin hall study i'm responding right now let's let him respond then we'll go to kevin hall later yeah so um what do you think about what he's saying about sugar and increased rates of diabetes and that this is the cause yeah i mean so let me put it this way we don't have any evidence supporting

what he just said so that is a story that is not supported by evidence. Now, does that mean that it's definitely incorrect? No, I cannot say that that's definitely incorrect. Same way I can't say it's definitely incorrect that cosmic rays cause obesity. But, you know, I'm going to use a Christopher Hitchens quote here. That which is asserted without evidence does not require evidence to refute. And that's the way I feel about this particular story. But, you know, there are cultures that consume large amounts of sugar and do not develop obesity.

We've talked about this also. Yeah, and we're going to talk about it again right now. So So this is reference number 21 on my blog. I'm going to talk about three different cultures, one of which we have not talked about, Gary. The first one is the Hadza, hunter-gatherers of Tanzania. This is a really interesting non-industrial culture. They, as part of their hunter-gatherer diet, eat a lot of honey. Honey is a very common food among hunter-gatherers living similarly to how our ancestors used to live. And if you measure their year-round honey intake, it's about 15% of their calories. So this is a major calorie source for them. That's about as much sugar as the average American eats.

And they eat fruit sugar on top of this. They eat a lot of fruit on top of that. And so they're eating quite a bit of sugar and the hadza men have about 12 body fat women have about 18 so they correspond pretty closely to our western ideals but isn't that high for hunter gatherers no not really i mean that's higher than me uh running around running around gathering food. Let me ask you this. How have you had your body fatness measured? I've had it measured a bunch of ways. Electricity. I've had this machine where you hold on to these things.

You stand on this platform. I've done it in a physician's office. I've done it with calipers. All the methods that you mentioned are not gold standard methods. So the gold standard methods are underwater weighing and DEXA. Are they underwater weighing these people on this island? Actually, I'm not sure. I highly doubt that they bring that equipment to this island.

Correct. But, okay, look, I can tell you that you can look up photos. I don't remember how they measured their body fat. But you can look. I am 12% as measured by DEXA. So I'll just tell you that you can look up photos i i don't remember how they how they measure their body fat but you can look i am 12 as measured by dexa so i'll just tell you that okay so you can get a sense of what 12 is by dexa um which is a gold standard method um so you can look at photos of these people they are very fit they're lean they're not like ripped you know they're not arnold schwarzenegger in peak form but they are no i understand, but it seems to correlate with a higher consumption of sugar, that they seem to have a higher percentage of body fat than the average hunter-gatherer.

If you look at a lot of the average hunter-gatherers, like a friend of mine does a lot of work with the pygmies in the Congo, and they're very lean. Okay, so the pygmies, that's the second culture I was going to cite that eats a ton of honey do they yeah the the if they're the same ones the mabuti pygmies of the congo um they eat up to 80 of their calories can come from honey during the rainy season so they also eat a lot of honey and are lean not just part of the year uh correct yeah for them it's part of the year the hadza eat it more consistently. And the Hadza have low levels of body fat.

Their cardiovascular risk markers are excellent. They don't have diabetes. But this is absolutely not like a controlled study in the consumption of their calories. Absolutely not. I absolutely agree with you. That's exactly the point I'm trying to make, is that when you have a culture that is eating a lot of sugar sugar but everything else is in place, they're doing everything else right, the sugar is not enough to make them fat. It's not single-handedly enough. I'm not saying it doesn't contribute.

I think sugar does contribute. Just to be very clear, I think sugar does contribute to obesity and diabetes and cardiovascular disease, but it's not single-handedly responsible, as Gary has argued. So the third culture is pretty interesting, the Kuna of Panama. And the reason they're interesting is that they actually aren't eating honey. They're actually eating white sugar. So they're a culture that they live primarily a non-industrial lifestyle. They're farmers and hunter-gatherers. But they do a little bit of trade.

And one of the things they trade for is sugar, and they eat sugar-sweetened foods as well. So like donuts and pastries, and they drink soda and Kool-Aid. What is their lifestyle in terms of like what are they? They have a natural lifestyle. They are hunter-gatherers and subsistence farmers so they're you know living a physically active natural lifestyle so this is the problem in comparison with any westernized civilization that you you burn off so many more cowards i 100 agree with you and i think that is exactly

the point i'm trying to make is that it's more complicated than just sugar. It is more complicated than just sugar, but with a normal lifestyle, it may not be. The thing about burning of the calories is also the glucose demands, the glycogen demands on the muscle. You're not just existing like the one of the problems with western lifestyle is that many people are just existing they're sitting in a chair they're walking to a desk they're sitting in their car they're not doing anything to burn any of this shit off so even if you have like if you get a baseline of a minimal amount of calories that you require for the day i I think what Gary's getting at is that if you have this lifestyle, the lifestyle that

many of us have, and then with that lifestyle consume sugar, that you're going to get fat. I don't think you can compare that to athletes. And in that respect, I don't think you can compare that to hunter-gatherers because you're requiring a much more significant load on your body. Like when I – I did this Sober October Fitness Challenge with my friends during October, and I was working out four hours a day. And I was fucking eating everything that moved. I was drinking soda. I never drink soda.

Yeah. I was eating cookies. I didn't gain any weight other than muscle i didn't get any fat at all yeah and i was eating a terrible fucking diet but i was going crazy when you're trying to stay alive and you're running around plowing and growing foods and hunting and gathering and fishing you're burning off insane amounts of calories. It's just the hiking that's required, the amount of exercise that's required. It's off the charts in comparison to a standard Western lifestyle. We are on the same wavelength here.

I mean, I completely agree with you that it is more complicated than just sugar. But if you read what Gary has written, and please correct me if I'm wrong here, Gary argues that sugar is the primary cause of obesity and that physical activity does not matter, calorie intake does not matter. Do you think that physical activity doesn't matter? I think it's a, no, I don't think it makes a hell of a lot of difference for fatty, when we're talking about the cause of obesity, I don't believe obese people get obese because

they're sedentary. But let me put it this way. So if you take someone who's an elite athlete and they start consuming a lot of sugar, but they ramp up their exercise accordingly. Like say if someone does what I did during the Sober October, they're working out three, four hours a day every day. You don't think that they have higher sugar demands that their body would just burn that off no absolutely i think that if there's a real benefit to exercise it's burning off the carbohydrates you consumed and and you need less insulin to do it can i respond to the kuna get back to them for a second okay i mean one of the the issues i have with

stephan is he writes off my stories as stories, which they are. All science begins as stories. Hypotheses. And then what you do is go look for the evidence. And then he quotes studies and refers to it as evidence as though this is somehow by calling it evidence. And we had this discussion a year and a half ago, and you didn't disagree with me at the time, and it had no influence. So I'm just going to read from the email I wrote to Stefan. Okay, go ahead.

Oh, boy. No, it's fine. We're reading emails. It's gotten to that point in the conversation. Yeah, indeed. Well, because I'm not only going to read from the email. If I have time, I'm going to read from your book. Read the Kuna.

The study you cited is interesting. Okay, so this was a study that professed to measure sugar intake of this population on an island, Aligandi, and compare it to the population in Veracruz where they had emigrated. And I say, but their added sugar intake on Aligandi, according to figure one, is 25 teaspoons per week, plus the equivalent of 24 ounces of sodas. That's 78 grams if it's Coke, 32 ounces of 24 ounces of sodas. That's 78 grams if it's Coke. 32 ounces of Kool-Aid. That's 96 grams.

I said I'm leaving out the cup of a sugar cane because I don't know what that is meant or how they assess it. One way or the other, it's not processed sugar. So it's roughly 274 grams of sugar per week or about 32 pounds per year. Now, that alone is very low intake, and we don't know how it changed over the years. We have no idea if it's increasing recently or been low for years. So, you just use the Kuhn as an example of a population that eats a lot of sugar and stated it dogmatically, but that lot of sugar is 32 pounds a year. And then I said, wait, hold on. I thought you did. That's what I heard. If we believe the study, the Kuna and Veracruz are consuming roughly the same amount, but I'm not sure I believe the study when it comes to the Veracruz population. move into the city, and they consume more sugar back where

they used to live because they trade for it than when they get into the city. So five glasses of Kool-Aid, no candy, no ice cream, nothing. I'd like to know more about the urban Kuna before I accept such an analysis as valid. On top of this, as they say, the analysis is done mostly of women because, quote, the women were available to study because they were at home during the day, unquote. So what were the men consuming and what were the children consuming when they weren't at home? And was there something magical about this freak food frequency questionnaire and these researchers that they captured it accurately? So this is what science is. You have studies.

You have evidence. And the question always is you've got competing hypothesis. Does this evidence really speak to the hypothesis? And one of my issues with Stephen, it's what provoked our initial discord, is that he's constantly citing studies that don't actually, either they only speak to one hypothesis, like the overfeeding study, or they're poorly constructed and poorly done. So even this HOSDA example with the honey is something we discussed in email very kindly, and we went back and forth. And I said, I don't actually think it's a refutation, because the hypothesis I'm defending

here, the case against sugar, is you add sugar to any population's native diet, and you get epidemics of obesity and diabetes. So here's a population that's been eating honey for maybe thousands of years. In fact, when they emigrated to this area, they may have added honey to their diet and had obesity and diabetes then. And as Stephen points out in the book, obesity and diabetes in a hunter-gatherer population is a death sentence for the child and for the mother who gives birth. So you're going to very quickly weed out anyone. So again, it just comes back to this question of does this actually,

is it a refutation of the hypothesis that I found a hunter-gatherer population that eats a lot of honey and isn't fat? And the answer is, I don't think so. Stephen thinks it does. You could flip a coin. All of this can be settled with experiments. One of the experiments we did at NUSI, so one of the metabolic problems that goes along with obesity and diabetes is non-alcoholic fatty liver disease. It's endemic. It used to be 20 years ago, if you had fatty liver disease, the doctor would, and you told the doctor you didn't smoke, they would assume you were lying. Now it's so common and so common in children and particularly common in Hispanic children that it's clear it's not caused by alcohol. And the question is what causes it?

Because if you could create a fatty liver with a macronutrient, you could probably create insulin resistance as well. And then this whole slew of disorders, including obesity and diabetes. So my not-for-profit funded a pilot study where we just took 40 kids by the researchers at UC San Diego and at Emory University in Atlanta, took 40 kids who had non-alcoholic fatty liver disease and randomized them into two groups. In one group, we gave them, the entire family, all the food they needed so they could overeat to their heart's extent, but no added sugars in their diet, no sugary beverages. And this study was published in JAMA four months ago,

and it just said, get rid of the sugar in the diet, the fatty liver disease resolves. You know, it was pretty simple. It tells you nothing about mechanism. The kids lost a little bit of weight. Maybe it was a weight loss. The conventional wisdom would be they just ate less, which I wouldn't be at all surprised because they probably didn't like the food as much without sugar in it.

But these are the kinds of ways you could test these hypotheses. And problems I have with, like, the meta-analysis, getting back to Kevin and Hall, there's two ways you could do science. You could say, let's look at all the junk that was done for 30, 40, 50 years. Let's find everything we can that even vaguely speaks to the experiment and ignore any quality of the study. So if it maybe asked, it asked this question, like, we want to know what happens when people do this, but in doing this, we switch their

fat intake around, fat and carb intake around. And then we can throw all that garbage into a meta-analysis. And the one thing I'm pretty confident is they did a poor job because the one study I looked up, the one with the biggest effect. They mistook kilojoules for kilocalories. So they reported a 400 kilocalorie decrease in energy expenditure on the low-fat diet. When was a 400 kilojoule, which is, what's that factor? You know these numbers. 0.8, 0.18 or something?

Several of the other studies were Jim Hill studies. We've talked about Jim Hill. The biggest studies were Jim Hill. And the way we approach it at the not-for-profit is say, you've got to understand what the question is, and you've got to design an experiment to get the right answer. So when Stephen dismissed this Harvard – You've got three names for him now. What's that? Stephan, Stefan, and now Stephen.

Jesus Christ. DNA. I can't get DNA right. Dr. DNA. Can I just do that? His name's Stephan. It's really easy. Stephan. I can't do it, dude. I just don't get names. My name's Joe. Hi, Gary. That I know. Hi, Joe. And Stephan ultimately rejected this study.

It's about a $12 million study that was done at Harvard based on Kevin Hall. So these are two names. It's about three people out there who are convinced that everything people like me are saying is wrong, or not everything, but most of it. And they keep coming up over and over again. wrong, or not everything, but most of it. And they keep coming up over and over again. So Kevin Hall claims that he has refuted the carbohydrate insulin model in his studies. So when a study comes out supporting it, he works to find out why that study's wrong. We all did the same thing. I did the same thing right here with the Kuna study, explaining why I don't find it meaningful. But anyway, that's the thing. The goal is to do the right study because ultimately, you got to remember what's on

the line here. We have obesity and diabetes epidemics. I mean, tragic shit is going on out there. I mean, people, you know, these are ruining lives. They're overwhelming the healthcare system. And the argument I made is that for the past 50 years, basically people have thought a lot like Stephan is thinking now, Dr. Guyenet, and that there appears to be another story that could be true. And what we have to do is find out if it is true because people are dying out there. Stephan? say is that this alternative explanation that gary is talking about has already been investigated intensively including studies that were funded by his own organization nusi two out of the three studies that have been published on that were clear reputations of the hypothesis and no no no i'm responded here i know i know but you've got to represent the studies correctly gary gary gary

i representing them according to your beliefs is not representing them correctly okay I'm responded here. I know, I know, but you've got to represent the studies correctly. Gary, Gary, Gary, Gary. Representing them according to your beliefs is not representing them correctly, okay? Now, I've noticed a remarkable correlation between studies undermining your beliefs and you thinking those studies are garbage. And we should talk about Jim Hill and his studies a little bit. Because, you know, to me, just saying this guy has a conflict of interest and then insinuating that that makes the study bad, if you can't actually find a problem with the study itself, these were very rigorous studies. If you cannot

point out a specific problem with the study, it was designed with an assumption. It was designed based on the assumption it was supposed to test. It wasn't designed how Gary wanted it to be designed. If you cannot find a problem with that study, then you can't just dismiss it by making these insinuations that the person had a conflict of interest, okay?

I explained to you the problem with the study. Okay, that's great, Gary. Now, let's go back to the Kuna. I didn't realize Jim Hill had done it at the time. All right, you're going to be able to respond in a moment. Now, the Kuna, I think we should really get back to this issue, this non-industrial culture, because the primary basis for Gary's book, The Case Against Sugar, the primary observation that underlies Gary's belief on this is this observational, belief on this is this observational correlational thing that cultures, when sugar gets into these cultures, they become fat. And that is the common thread and in obesity. And so what I'm doing is

I'm pointing out a culture where sugar came in and it did not make them fat. And that's one of three cultures. I haven't even looked that hard. Okay. These are just three cultures that I came across. It's probably a bunch more that are eating high levels of sugar. But they're eating high levels. The other two are obese. And I think honey is the same. And again, Joe explanation is right on point. There's a lot of other things going on in these cultures and it's more complicated than just sugar. That's exactly my point. Now I want to talk about the Cuban economic crisis. This is reference number 22. From 1989 through 1995, the Cuban economy collapsed, and the price of food went way up, the price of gasoline went way up, and so people started focusing on these really cheap foods.

Vaseline went way up. And so people started focusing on these really cheap foods. Cuba was a major sugar producer at the time. I don't know if they still are. And so the intake of sugar went way up. Intake of refined carbohydrate went way up. The diet became 77% carbohydrate, primarily white rice and sugar, 28% sugar of their total calorie intake. So that's like double what Americans eat. Now their calorie intake went down and because of the lack of gasoline, people got really physically active because they had to walk everywhere. So now,

again, if this is, this is a situation where we can test Gary's hypothesis. If Gary is right and calories don't matter, only refined carbohydrate and sugar matter, obesity should have gone through the roof in this population over that period of time. What you actually see is that the prevalence of obesity declined by half. So there was a 50% decline. It went from 14% to 7% over the period of this increase in sugar intake, increase in refined carbohydrate intake. And you might think, well, these people are just starving like crazy,

and that's why obesity rate went down. Well, we actually have evidence on the rate of underweight as well, and so we can check on that. The rate of underweight increased only slightly. It went from 8% to 10%. And so we know these people weren't just totally starving. And what happened then was as the diet rebounded, as the economy rebounded and the diet rebounded and their diet shifted away from these refined carbohydrates and sugar and back to the normal diet that was higher in fats and lower in carbohydrate, lower in sugar, the obesity rate went right back up as soon as

they went back to their normal diet. And so I find this- Because they were not walking as much. Yeah, it was the exercise and also just their diet became richer again. I mean, if you're eating a diet, that's a very poor diet, eating white rice and sugar. I mean, if you're eating a diet, that's a very poor diet, eating like white rice and sugar. I mean, it's not like, if that's most of what, if you're sitting there and on your plate is white rice and sugar, you're not going to be eating a ton of that and getting fat as opposed to eating a richer diet with more varied foods. And so, this is a case where you have an entire country testing Gary's hypothesis and finding that basically the opposite of what his hypothesis predicts. Gary?

Let's go with when he was refuting the studies and you wanted to oppose that. This is a level of discourse that I didn't really want to get into because that's a study that I'm going to have to read. He's right. I'm going to read it to try and figure out what the problem is. I remember looking at that study and thinking there wasn't the kind of data you're citing. Maybe there's multiple studies put together, but the one study I looked at, the kind of data you're citing wasn't in there. This is, again, a problem. References are on my website, so have at it.

No, I will, but we'll be off the air by then. The beginning of his, when he started talking, he was referencing some studies, and you had a problem with that? Well, this whole, it's a game people play. And again, it's why basically in my book, I try not to get into the he said, she said studies, because you never know how well they did. I think we both agree that there's a reproducibility crisis in science, and some huge proportion of the studies are just wrong. Whether they're experiments or observations, people sometimes aren't very good at what they do. And so anyone in either business, you have to, Stephen likes to say, I have no

evidence. Stephen, damn it. But simultaneously, people accuse me of writing a 600-page book with 150 pages of references that was too long to read. So there's clearly evidence for this observation and this hypothesis. My issue with Stephan is that he speaks as though he knows with this authority. And so, again, I would like to just read a little bit from your book because as I was prepping for this, I was— Before you do that, though, he was referencing studies— the cuban situation i don't know what the reality is before that when when he first started talking he was referencing things that you were stating that he was saying what were you saying that uh the the the organization that supports him actually

refuted oh that was the gym health studies yes No, no, no, no, no. The Newsy studies. No, we're talking about the Newsy studies. The first two of which and we can get into detail on this, on how those refuted Gary's beliefs. And I would say Gary's about the only person who thinks they did not refute his beliefs.

The scientific community is pretty unanimous. You can respond, but could you please say what the study stated? Well, let me do it before he. So the first study is a pilot study that depends what you look at to depend whether or not it refuted your belief. So, again, you have to understand this world. There are researchers who believe one thing. Kevin Hall at NIH tends to believe that obesity is an energy balance problem and people get fat because they eat too much.

I hope I'm doing Kevin justice. And then there's David Ludwig and his colleagues at Harvard who tend to believe what I believe. And we funded them both to do studies. And Kevin Hall's study, if you believe Kevin interpreted it correctly, was not supportive of this model that carbohydrates are ultimately driving insulin and insulin is driving up fat accumulation. And then the David Ludwig study reported the opposite. And David has criticized Kevin's study, and Kevin has criticized David's study. And this is the nature of science. This is what you do in science. You do an experiment, people critique it. Ideally,

you do another one. Kevin has decided, well, Kevin is doing another one. I think he's asking the wrong questions, but I just saw the other day that he's doing another experiment. Today, the middle study was a free-living diet study done by Christopher Gardner at Stanford University. And the original idea was 600 people randomized to either a very low-carbohydrate diet or a very low-fat diet. And we funded it in part because we hoped that Christopher would be able to get people to almost a ketogenic diet on the low-carb side. And Dean Ornish, who promotes a low-fat diet, always complained that the low-fat diet wasn't fat enough, so hopefully they'd be able to separate out these two. At the end of the trial, they got pretty lousy adherence. Low-carb was about 25% to 28% carb, which is by no means a low-meaningful low-carb diet.

Pretty typical. In free-living studies, and the low-fat was about equal. What they did, which it's funny, we realize this on one side but not the other, they told the low carb group not to eat sugars and refined grains, which are, by my hypothesis, the most fattening carbohydrates. And they also told the low fat group to not eat refined sugars and refined grains. So they basically removed the most fattening parts of the diet from both arms of the study. It's funny.

We knew they were going to do it with the low-carb group because you have to, and my colleagues actually knew they were going to do it with the low-fat group. I didn't know that when I found out. I was stunned because now you're testing two diets. Neither one of them have sugar or white bread. So now you see similar weight loss with relatively poor compliance. Why would they do that? That doesn't make any sense with the low fat diet.

Well, their argument, and we talked to Chris for a lot of his argument, he was afraid. There were two things. He wanted the diet to be healthy. So a healthy diet in 2015 has become a diet that doesn't have sugar and white bread in it. So he wasn't going to promote sugar and white bread to one diet or another. How long was the period of time where they were studying these people? They were on the diet. They were supposed to be on the diet for a year.

Okay, that makes sense then. Yeah. So the question is, again, would you expect to see a difference? I can send you an email I wrote to my NUSI colleagues in 2015. I could read it. When I found out about this low-fat thing, saying, this is insane. He's removed the – both groups are carbohydrate-restricted. Right.

So you could think of it as a low-fat, carbohydrate-restricted diet and a high-fat, carbohydrate-restricted diet. And then he kind of got the same answer, which could be for any reason whatsoever. There's a paper, I don't know if I can, well, I'm not going to talk about it. It's bad enough talking about the ambiguous studies that have been published without getting into unpublished research. So people see this. The New York Times, for instance, did two stories on it. One of them said it's not about calories, it's about the quality, the sugar and the refined grain, because both groups restricted sugar and refined grains and lost weight. And that was written by a reporter who tends to believe what we believe. And the other article said it's all about the calories, because

both groups ended up, on average, eating 500 calories each it ends up from a scientific perspective being a poorly done study even though we funded it i'm not it's just it didn't answer the question you said 500 calories each 500 calories less and that's actually self-reported so it's not so it's not particularly meaningful so again these are i don't like using it's whether that's a complicated study because it's low in sugar. Well, and it's also free living. Yeah. So both sides are low in sugar.

Both sides are not eating processed food. There were two full differences in total carbohydrate intake. Okay. So even though they were both not eating as much refined carbohydrate, there were still two fullfold differences or greater over the period of that study in total carbohydrate intake. If you believe the food frequency questionnaires that you just said, we don't know whether we have. Carbohydrate.

And you could be talking about vegetables. You could be talking about fruits. Well, these are healthy carbohydrates that they had primarily in this study. Can we agree that that study can be interpreted from virtually any way you want it, especially because it was a pre-living study? No, I definitely don't agree with that. Now, what we will agree on, I'll agree with you on this,

is that refined carbohydrates and sugar are the most fattening type of carbohydrate. That we can agree on. Oh my God, we came to an agreement? No, but the question is why? Is it because people eat too much of them? Here's the thing. If if you believe gary's hypothesis now any kind of carbohydrate increases insulin levels some do it more than others refined carbohydrates do it more any kind of carbohydrate

increases insulin levels relative to fat okay and so if that is true And these groups And that matters for fat loss These groups had two full differences In carbohydrate intake Even though it was predominantly healthy carbs You should have seen something You shouldn't have seen the exact same amount Of weight loss in these two groups, right? Right, but they're not high in sugar

Correct Isn't your argument as always That's sugar That's the other part of the argument Which is you take away the sugar And that was the problem part of the argument, which is you take away the sugar, and that was the problem with one of the problems with the energy. Yeah, the argument I'm making, and Stefan's completely right. I'm defending my hypothesis, okay?

I see a study that he does the same thing. He did it here. We all do it. You see a study that disagrees with you, you find the reason why they're not. Believe it, and every study ever done has plenty of reasons not to do not to believe that's why independent replication is something you always wanted you get another group to do the study ideally a third group people come in they criticize the study then you do it again yes and again and again and so you know what i was trying when we even

when we started the nutrition science initiative the choice that was a non-profit, the choice of the word initiative was to get nutrition researchers to, in effect, stop using these garbage, poorly designed studies to come to conclusions because they like or dislike the interpretation, but try to get them to think the way harder scientists would. In developing studies, it asks precisely the right question. scientists would in developing studies that asked precisely the right question. And then so even the pilot study that was interpreted as not supporting this hypothesis, and again, you could argue that for an hour and nobody's going to care, that study was not randomized.

So a non-randomized study, you can't infer causality. That's why it was a pilot study. One of the many reasons it was a pilot study. The people who think this carbohydrate model. So when we talk about the carbohydrate-insulin model, it means carbohydrates are fattening. That's the basis of it. Bread, pasta, potato, and sugar may be the thing that's necessary to add to the diet to make all these carbs fattening. Because sugar, as we talked about this a year and a half ago,

the fructose molecule is metabolized in the liver. It's linked to fat accumulation in the liver, which is linked to insulin. The way you're squeezing your stomach fat while we're talking about this. I got to work out, dude. I'm just bored. For these experiments to be done right, they have to be tested right. You can't use poorly designed experiments and every experiment ever done. And so what we've tried to do is keep working towards better experiments.

There's now a new version of the Ludwig experiment being done at the Arnold Foundation. Lauren John Arnold funded to the tune of, I think, $13 million. And whatever that study finds, Kevin Hall will probably find a reason, look in it, and find a reason to question it. And ideally, they would be working together so that you come up with the criticisms before you've spent $13 million. But this is how science works. My job was to tell a good story, as Stephan would say. And I believe people who read the books can judge whether it's a good – Am I convincing in arguing that you add sugar – there's counter-evidence to everything. There wasn't counter-evidence.

It wouldn't require a journalist to come along in 20-whatever-it-is-19 to make these arguments. Let me ask you this because this is something that you've admitted to, something you said rather. Why are sugary carbohydrates the most fattening? Well, if this hypothesis is correct, I think you would say that they trigger a food reward or they are food reward. Yeah, absolutely. Wait, wait, wait. Let me just finish. I would say the counterargument is that they create a hormonal milieu in the body that over-responds to insulin. And insulin, what we haven't said is if you look in a textbook for fat metabolism and

fatty, you know, what causes fat storage, insulin is the hormone that primarily regulates fat storage in your fat cells. So the idea is you raise insulin and the sugar because of this half of it being fructose and that mostly being metabolized in the small intestine and the liver, seems may indeed cause insulin resistance. And if it does, you over-respond insulin. So one is a peripheral explanation, not that people don't love it and they don't want to, you know, over-consume it, whatever that means. And the other is a central explanation.

Yeah. So, I mean, sugar is a factor that makes us want to eat foods, right? I mean, this is one of the many food properties, and I would love to talk about this more, that cause dopamine release in the brain. And dopamine is a chemical that sets our motivational levels to do certain behaviors. So the reason we become addicted to drugs is that they go in the brain and they stimulate dopamine release and that reinforces drug seeking behaviors right but this is just causing you to consume more correct but you're saying that the actual amount let's say if you have the same amount of carbohydrates that are sugary carbohydrates versus the same amount that are vegetable carbohydrates the sugary carbohydrates are

going to be more fattening no no i didn't say it was independently of calories. It's entirely dependent on calories. Yeah, correct. And we have randomized controlled trials demonstrating this. So if you look at the randomized – by the way, we're not operating in an evidence vacuum. There's tons of randomized controlled trials on sugar. Can I ask you this? Yeah. These randomized controlled studies, are they short-term?

Well, it depends on how you define short term they're not lasting years and years and years isn't the issue though long-term chronic effects like that seems to be possibly but let me put it this way you know if you believe that insulin is the cause the effect of insulin on fat cells happens almost immediately. So insulin, I'm not aware of any mechanism of insulin on fat cells that takes more than a few hours to occur. And so if you believe that insulin causes obesity, this should be happening immediately. You shouldn't have to wait months and months for this to occur. No, that doesn't make any sense at all.

No, it does make sense. Why doesn't it make sense to me? You make sense. Why doesn't it make sense? It doesn't make sense to me. You eat carbohydrate. Why doesn't it make sense to you? Well, because again, he's kind of making this up as he goes along.

So the idea is... Well, explain why it doesn't make sense without insulting him if that's possible. Has he not been insulting me? Or am I just biased? I realize that everything is perspective. Well, I don't necessarily think he's insulting your stories, not you personally.

But why doesn't it make sense to you what he's saying? Okay, so the idea is when your insulin is elevated, you're storing fat, right? It depends on what you mean by that. See, you do a little bit of bait and switch here. No, no, no mean by that That's not See you do a little bit of bait and switch here No no no that's an insulin Just answer the question If it's not true clarify

Well it depends What do you mean by store? I mean your fat cells are accumulating fat When insulin is elevated Do you mean accumulate like Like next day you'll have I called on to fat Like it inhibits

Yeah that's incorrect It stimulates lipoprotein lipase, and it inhibits hormone synthesis. We should really talk about this, because that's incorrect. It's in the textbooks. Oh, yeah. We'll talk about what's in the textbook. Don't worry, Gary. Jesus.

Okay, so you don't believe insulin. Well, just give me your position, and I'll let him refute it. It's here. But just say it. No, no. We'll just show it, okay? Because position and I'll let him refute it. It's here. But just say it. No, no. We'll just show it, okay? Because, again, you're going to say it's not in here. So I have the same textbook.

And then we'll let Joe here. Suppression of fat mobilization by insulin. And there's another graph that is stimulation of fat mobilization. Congratulations to all of you people That are listening to this I know we're in the weeds scientifically Let me just say This is going to take a long time

So we agree on the molecular mechanisms We agree on the molecular mechanisms The impact of insulin On enzymes and fat cells What we disagree about Is the implications of that And I think that's what we should talk about the implications of that and yeah and i think that's what we should talk about that's true because nowhere in that textbook does it say that insulin

regulates the total size of body fat stores absolutely absolutely that is that is something that you have added on to absolutely that mechanism would you like to know the conversation I had with the author of that textbook? No, not right now, actually. So, the, now, the... Let me tell you about the conversation I had with Keith Frey. No, actually, Gary, let me finish explaining this. I was actually in Oxford. We talked about this for three hours. Gary, can you stop interrupting me, please?

Okay. Now, let me explain. So, insulin essentially does have effects on enzymes that cause fat cells to take up more fat and to release less fat. So that's the part that you're right about. That's what that textbook talks about. Now, that does not mean, that does not imply that insulin causes fat storage as in the accumulation of fat from day to day. And let me explain why that is. So insulin is basically a traffic cop that allows your body to burn the fuel that you just consumed. So when you eat a diet that's high in carbohydrate and low in fat, your insulin goes up,

your body restricts the fat from going out of fat cells. It turns that down, not off, but down. It causes less fat to come out of your fat cells, and then your body's burning carbs. That's what you just ate, right? Now, if you eat a diet that's high in fat and lower in carbohydrate, you secrete less insulin. Those effects don't occur on your fat cells, and that allows your body to burn the fat that you just ate. But at the end of the day, the amount of fat that you have in your body is the amount that you ate minus the amount that you burned. That's what determines the amount. This is just arithmetic, right?

Amount that you ate minus the amount that you burned. And if you eat a low fat diet, you're not eating much and you're not burning much. You're in the same place as if you're eating a diet where you're eating a lot of fat and burning a lot of fat. And the way we know that's true is because varying the amount of carbohydrate and fat in the diet makes no difference to body fatness in randomized controlled trials. That's why we know that what I just said is correct. No. So, first of all, it's one randomized controlled trial. It's Kevin Hall again. No, I'm talking about a meta-analysis of 20 randomized controlled trials. We can't talk about the meta-analyses.

We decided that I think, you know, that the... What's wrong with the meta-analysis? You get every crappy study ever done. He doesn't like who did it, basically. No, no, no, no. I don't care who does it. I don't like meta-analyses. I don't like the concept of them.

I think it's one of the problems with modern nutritional and medical science is you do crappy studies, generate garbage, and then you sift through the garbage and say, I can find a truth in here. And the answer is do better studies. The answer is always do better studies. You can't do – meta-analyses exist for everything. The issue is just as a simple one. Remember, we're talking about the 10 calories a day. So when you said the difference between the fat burned and the fat stored or the fat consumed and the fat expended has to be 10 calories a day. That's what we're talking about, 10 calories in the fat tissue. Okay? I consume 1,500 calories a day, and I somehow metabolize or excrete 1,490, and I guarantee that no such study was ever so carefully done. Can you cite evidence to support this thing you're saying right now? Well, you could take, for instance, the Energy Balance Consortium study, the Kevin Hall study that we've talked about. There are two things that happen when you put people on a ketogenic diet.

Among other things, you generate ketones, and you lose ketones in the breath and in the urine. And one of the things you have to do in these energy balance experiments is measure calories lost through fecal material. Who knows? Maybe you jack up the fat consumption. Maybe they lose more fat calories when they shit it out. Or maybe you jack up the fiber. So you think calories matter? I think when you're measuring the fat balance, which you're talking about, you have to measure the amount of fat in and out. And so I'm giving you an example in response to your question was because you gave me an example. In that study, they didn't do either of those measurements. They modeled one and the other one, they couldn't get the assay to work after a year or two years and gave up on it.

And so you just don't know. But getting back to this question, we're talking about somebody storing 10 calories of fat in their fat cells. Let's never get away from that or 20 calories. And so the question is always is this mechanism capable of explaining the 20 calories or is the – What did you find from looking in that book? Well, it's essentially what he was saying. And insulin inhibits fat mobilization from fats. Well, I could read it if you want me to read it. I mean, Gary and I both agree with what's in that textbook.

You can read it if you want, but I don't see the point. Yeah, it says insulin restrains fat mobilization through two mechanisms. So suppression of lipolysis. Is that right? Yeah. Lipolysis. So mechanisms are described in the text and the stimulation of the re-esterification of fatty acids within the adipocytes. Adipocytes.

Adipocytes. Adipocytes. Fat cells. Fat cells. Fat cells. Note that the same process of esterification will also be simultaneously incorporated fatty acids from circulating triglycerol. Triglycerides.

Yeah. Triacylglycerol. Triacylglycerol, right. Released by lipoprotein lipos. Limpase. Limpase. That's enough, Joe. Limpase.

L-I-P-A-S-E. Into stored triacylglycerol. Yeah. So let me, just to explain this briefly. A lot of big words. The argument I've been making, and others, is that insulin inhibits fat loss. Fat mobilization. Like if you're a fat cell, and you see insulin, you hold on to your fat.

Right. Kind of that simple. Stefan's absolutely right. This book, which we're talking about, is a metabolic regulation of human perspective. It's written by Keith Frayn, who's a retired Oxford professor, who's a wonderful man. And he was the world's leading authority on metabolic regulation, how your body controls its use of fuel and orchestrates storage and oxidation. And in this book, Keith Frayn talks about how insulin determines fat accumulation in fat cells. Not accumulation. Whatever, fat storage in fat cells. Not accumulation.

That's not the correct word. Whatever, fat storage, fat storage. Dynamic fatty acid trafficking in and out of fat cells. Okay, thank you. So the first time I ever interviewed Keith was for a piece I was doing for the Journal of Science on insulin resistance. And we spent about an hour on the phone, and he explained to me for 20 minutes all the ways insulin traps determines fatty acid trafficking across the fat cell membrane. And you raise insulin, you accumulate more fat on the short term. And then we got to obesity, and he said, well, obesity is caused by people eating too much.

And they said, well, obesity is caused by people eating too much. And I said, Keith, when we were talking about why fat cells get fat, it was all insulin-mediated. And when we were talking about people get fat, it was this eating too much thing. And you switched mechanisms on me. So my assumption is the same reason people get fat is the same reason their fat cells get fat, and you've got a whole lot of, you've got this disorder, metabolic syndrome we're talking about, which includes not just problems with your blood lipids,

but it includes getting fat or your waistline increasing, and it's an insulin resistance-related disorder, which means your insulin is elevated. And again, this is where we end up with two hypotheses about why insulin is elevated. But if, for instance, sugar can elevate insulin, you end up with metabolic syndrome. You're in fat storage mode. That's the terminology of diet book doctors. So now you're storing fat and you only have to do 10 calories a day. 20 calories a day, you're going to get obese. And it's insulin-mediated and insulin's responding to the carbohydrate content of the diet primarily. And that's it.

And when I said this to Keith, you've got one mechanism for why fat cells get fat and a different mechanism for why humans get fat. And I'd like to talk about this overeating concept. He said, you know, I never thought of that. I mean, the guy had been in the field 40 years and he lived maybe 50. And then I had a long conversation with him. I was back in Oxford when I did that insane Alan Aragon debate. I stopped off at Oxford on the way to Manchester and we had a long conversation with Keith. And I said, look, what I want you to do is just come up with a hypothesis of obesity from the fat cells perspective, right? Shed your brain centric, energy balance centric thing and ask yourself, what does the fat cells see? And if

nothing else, ask a student to do it as an experiment. I mean, that would be a great thought experiment for a kid. What's going to make a fat cell fat? And then our assumption is going to be that's what's going to make a human fat. And Keith said, he literally said to me, he was retiring and he was going off to garden. I kind of envied him. But he said, you know, I just can't, I can't put energy balance aside. You're telling me to not think in terms of intake and expenditure, and I can't do it. And I mean, wonderful man. He literally, and this is, again, what I've been arguing is all these people are so, including Stefan, who was learned in this world,

they're so locked into this thinking that obesity is this energy imbalance, and they can't get away from it. So everything they do, everything they interpret, and when Stefan says there's study after study, and there's 20 randomized control studies, and it's sort of I'm going to shovel the evidence on top of you, and I'm saying, look, I guarantee if we go through those 20 studies, they'll be just like the Jim Hill study.

They assumed energy balance was the cause, and then they wanted to see what caused energy imbalance, and they started with the wrong hypothesis. They're trapped in a paradigm. We've all seen this. Can I respond to this? Please. Okay. So, Gary, I pre-ordered your book. I have a copy of your book right here, Good Calories, Bad Calories. I pre-ordered this in 2008 because I was so excited to read this book. Yes. And you emailed me. I tore through it and I was so persuaded when I initially read this 10 years ago that I ate a low carbohydrate diet for six months because I thought the carbs were going to make me fat and give me diabetes. So I was fully immersed and

convinced by your perspective when I read this book. And you signed this book. I have your signature. We had a very nice dinner together. And the thing that caused me to go away from that perspective was when I actually started investigating the evidence on my own, underlying these ideas. I started doing my own research. I didn't take your word for it.

I started doing my own research. I didn't take your word for it. I started doing my own research in the lab as well and actually doing real scientific studies. And I found that it did not line up with what you were saying in your book. And what I ended up realizing about good calories, bad calories is essentially your arguments primarily rely on historical narratives and speculation. And there's very little of actually saying what is the most pertinent scientific evidence to answer this question and what does that evidence have to say. It's mostly historical narratives. And honestly, you know, I'm going to try to say this in a non-insulting way, but I will simply say that others who have looked at

the same historical evidence have come to different conclusions than you have um and that includes me in the places where i've looked at the historical evidence and so um i think that you know this idea that i am like locked in some paradigm and can't see what you're talking about i was there gary i am post so let me okay so let me let me let me just it was interesting because you're we're gonna wrap this up soon so let's uh have we really gone there three hours almost um remember when you i was drove up here from san diego this morning and i was listening to stefan on a different podcast and you were talking about how your eating behavior differed on low carbcarb diets versus the higher-carb diet you eat now.

And you talked about your resistance. It was easier to fast on the low-carb diet. Correct. Okay. And you didn't really have an explanation for it. I don't have a very – well, anyway, go ahead. Yeah. So, again, the argument I've been making is there's two ways to look at everything.

So one way is the low-carb diet somehow because of, I don't know, food reward issues affects your urge to eat low-carb foods. And because of that, you don't hunger for them as much. And when you're on a higher carb diet, I think the way you phrased it on this other podcast was your body sort of tells you it's mealtime, so it's conditioned to mealtime better. So the alternative hypothesis here, the other way to think about it is on the low carb diet

his insulin levels are staying lower. And when they're staying lower, he's mobilizing fat and he's oxidizing that fat. And as you said on the podcast, even a 135-pound marathoner has enough fat in his body to run for a week. So the reason you're able to skip meals is because insulin is low. My wife is calling. She's probably telling me I'm getting shrill.

There's a different way to look at everything. That's the point I'm trying to, with every study. I mean, can you tell me evidence that, can you give me actual evidence that the lower level of insulin is the cause of not needing to eat those meals? No. Okay. I'm giving you a hypothesis. I'm glad you're being honest. Well, again, let's, no, let's.

Well, you're saying, like, we're talking about fasting, right? If you're fasting for a certain prolonged period of time, your body's going to go into a ketogenic state. We all agree with that, right? And that's the reason why it's easier to fast. Once you're in ketogenic states, your body starts burning off fat, and this is a widely reported side effect. Well, it's living on fat. It's metabolically flexible. You don't have to eat because so – but it's the idea that it's living on your fat is evidence

that you're getting thinner on that low-carb diet. No, because it's fat balance. It's the amount you're eating minus the amount you're burning. No, but the question is it's also the amount you're trapping, and that's what you keep leaving out. So if you have- No, that has been tested and refuted is what I'm saying. It has not been tested. That's what I'm saying. That's why been tested. That's what I'm saying.

That's why we founded NUSI. That's why we spent $30 million. That's why David Ludwig is doing another $13 million study. It has not been tested. When you feed people, whether it's overfeeding or underfeeding and you're causing weight loss or weight maintenance, the carb to fat ratio of the diet makes almost no difference. Let me give you another example.

There are many studies on this. The famous feeding study from the 60s, which I thought when you said Horton, I thought you meant Ed Horton, not T.J. Horton. So Ed Horton and Ethan Sims did a prisoner study. They literally, they wanted to get overfeed. Again, they're using their thinking in terms of eating too much. They wanted to first get college kids to gain 25% of excess body weight. This was in the 60s, and they couldn't get the college kids to do it, which suggests that college kids

were different in the 60s than they are today. So they used prisoners in the Vermont State Prison, and they overfed them. And you discuss this in your book. They could get these prisoners to eat 10,000 calories a day of excess carbohydrates. Excess calories. It was calories, not carbohydrates. It might have been calories. They couldn't get them to add more than 1,000 calories of fat. Okay. And they talked about this.

Some studies were crazy because they published in 15 different journals. So they interpreted the study. If you looked at pounds gained per calorie added, they gained more per calorie of fat than they did per calorie of carbs. But if you looked at how much they could eat, they couldn't add that much fat. And they could add 8,000, 7,000 extra calories of carbs. There's actually a line in one of the papers where they said they would eat 10,000 calories and then go to bed hungry, craving more carbs. So then the question becomes, again, is it because the carbs are doing something in the

brain to increase food reward, or is it the carbs are doing something in the body so that their body has figured out a way it can orchestrate, deal with this massive influx of carbs versus fat. But there's always two ways to look at it. And every time Stefan says there's masses of evidence, my job as a journalist was to go through and say, does this refute that hypothesis? And if it doesn't, we have to hold on to it. Because remember, we have an obesity and diabetes epidemic. And the kind of advice where we tell people to sleep better and eat less or avoid foods that they love, don't have pizza and ice cream,

it implies that the reason they get fat, even the overeating hypothesis. So you think they should be eating pizza and ice cream? What do you think? No, I think we would both say don't eat pizza and ice cream. Okay, don't ask questions like that. Thank you. There's something wrong out there, tragically wrong. We know if nothing else, I think you would agree with this.

So the whole low-carb movement, as you said it on this podcast, was that what I've done, if nothing else, is I've convinced people they could eat low-carb diets without killing themselves. So that's a good thing. Yeah, I agree. And I'm implying that with the, I assume with the sugar book, even if I'm wrong,

that getting people to eat less sugar is a good thing. So ultimately, these are good things that I've done. My overall contribution. Not entirely, Gary. Not entirely, because you're telling people that only carbohydrate matters. I'm telling people that only carbohydrate matters I'm not telling people only carbohydrate matters You have argued at length that calorie intake and dietary fat intake and physical activity

Do not influence body fatness and are not important You're explaining it the wrong way I'm arguing that Look at the model that we published that you contributed to and we signed off on It doesn't say anything about physical activity. It says that physical activity, dietary fat intake, and calorie intake are not important contributors to obesity and insulin resistance. Stefan, I refuse to believe that somebody who's obese got that way because they were sedentary. Okay.

Okay. In part, and again, it just requires. But what I'm saying is that there is harm in what you're saying, because, yes, we all agree that these carbohydrates are fattening, but you're saying that these other important things are irrelevant, and that's the dangerous part of what you're saying. No, no, no, no, no, no, no, no. What I'm saying about calories is it's the wrong way to think about it. So, wait, you think they do matter?

I'm saying calories are the wrong... Don't put words in my mouth. Okay, do they matter or not? I'm saying calories are the wrong... Do calories matter or not? Calories are a way to measure the quantity of food you're eating. You could use grams, you could use anything else you want. The question is, is it the right way to think about it?

Can you solve an obesity problem? Let me give you an example before we go. Let me just read you. So, excess calorie intake and physical inactivity are secondary to this process And not themselves determinants Of body fatness That is what you said In our Debate notes

I'm not putting words in your mouth here But that's different than what you just tried to give me Okay sure it is Okay let me read you something There just never seemed to be enough food To satiate Carl's growing body After school he would eat a foot-long sub Before his mother's home-cooked dinners

Even after having a hefty lunch Of homemade chicken, rice, and vegetables And his favorite snacks, granola bars And a bunch of crunch Okay A lot of calories We're talking about one person We are talking about one person

Yeah, how is this going to Well, I just want to know One of my problems We're talking about one person. We are talking about one person. Yeah, how is this going to differentiate? Well, I just want to know. We're wrapping this up and we're talking about one anecdotal. One of my problems with the whole overeating hypothesis is it's tautological. You don't know if someone's overeating unless they're fat, right? Incorrect. Well, this fellow, I just read you. You can measure their calorie intake and you can know.

I don't know what you're talking about there, Gary. We would eat a foot-long sub before his mother's home-cooked dinners, even after having a hefty lunch of homemade chicken, rice, and vegetables. Yeah, yeah, yeah. Again, that's one story. We're really getting in the weeds here. My point is, it's like, you cannot tell if someone's fat. You have no idea how many calories I consume, right?

I could probably get a pretty decent estimate, actually, based on published formulas. Okay. And then how would you know whether I was overeating? Remember, we're talking about 10 calories a day. No. It gets stored in the fat tissue. Well, that depends on whether you mean how you define that but um i i could look at your body composition and i could tell you whether you were overeating relative to a lean person yes because i have excess body fat correct yes so

without knowing if i have excess body fat you cannot tell whether i'm overeating which is the cause of the excess body fat, right? Doesn't that strike you as circular? There's nothing circular about it. Look, if you take somebody and you increase their calorie intake, carbs or fat, either way, they gain body fat. There's nothing circular about saying that calories increase body fat. I'm pretty confident that the fellow on this regular. And if you take someone who currently has obesity and you reduce their calorie intake, carbs or fat doesn't make any difference. They lose body fat.

So there's nothing circular about this calorie thing at all. But it does make it. No, no. I just see. I don't understand how you could possibly think that was circular. It's so simple and direct. So let me go through it one more time. Listen, you're not going through anything one more time.

We're going to wrap this up because I don't think we're getting anything done here. Yeah, neither do I. It was a lot of fun. It wasn't that much fun. It was. It was interesting. I mean, I don't know who to believe, quite honestly.

I think you both make some excellent points, and I think there's definitely some real legitimate concern that you have about his position and I think that your position has some merit as well the position about insulin and about carbohydrates and sugar this is a really long conversation and I think we could probably do this for another six days forget about hours I think if I would recommend I think people have to really kind of figure this out for themselves I would recommend Stephan please recommend your book

what is your book again? yeah the book is called The Hungry Brain and it's available everywhere Amazon all that jazz and Gary yeah it's good calories bad calories or why we get fat or the case against sugar.

I think we've just begun this debate. I think legitimately. It's been going on for 70 years. Yeah, I've got a lot of evidence here that I didn't have time to cite, unfortunately. Yeah, well, it was a long one. But thank you, gentlemen. Thank you. All right.

Thank you.