Joe Rogan Experience #1267 - Gary Taubes & Stephan Guyenet

1. 0:00 – 3:24

   Setting the stage: brain vs insulin models of obesity

   1. JRJoe Rogan0:00

      Four, three, two, one. (clearing throat) And we're live. All right, so to set this up, um, when Gary was on last, Gary Taubes? S- Stephan, how do I say your last name?

   2. SGStephan Guyenet0:16

      Stephan Guyenet.

   3. JRJoe Rogan0:17

      Guyenet.

   4. SGStephan Guyenet0:18

      Yeah.

   5. JRJoe Rogan0:19

      Guyenet.

   6. SGStephan Guyenet0:19

      It's like D-N-A.

   7. JRJoe Rogan0:20

      Like D-N-A, but with a G.

   8. SGStephan Guyenet0:22

      Right.

   9. JRJoe Rogan0:22

      Got it. Okay. Um, when you were on last, Stephan had, uh, 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. Took... There was a lot of wrangling, there was a lot of back and forth, and cat wrangling-

   10. SGStephan Guyenet0:40

       (laughs)

   11. JRJoe Rogan0:40

       ... but we got it. We're here. Um, give me your position on... This is all for, for folks listening, this is all about obesity and the m- the mechanism for obesity. Is that fair to say?

   12. SGStephan Guyenet0:54

       Yeah, yeah. So essentially, uh, the main points that we wanna talk about today are-

   13. JRJoe Rogan0:59

       Try to keep this a fist from your face.

   14. SGStephan Guyenet1:00

       Okay, sure.

   15. JRJoe Rogan1:01

       Just pull-

   16. SGStephan Guyenet1:01

       So-

   17. JRJoe Rogan1:01

       Just pull... You can move it around.

   18. SGStephan Guyenet1:02

       Um, what causes obesity and what causes insulin resistance, which is behind a lot of our, um, chronic diseases that are common in society.

   19. JRJoe Rogan1:11

       And please, uh, give us your background.

   20. SGStephan Guyenet1:14

       Yeah, so I have a, a BS in biochemistry, a PhD in neuroscience. 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, um, to become a science consultant, science communicator, and write a book called The Hungry Brain that is, um, my attempt to explain for a non-specialist audience what, uh, what causes obesity. And, uh, yeah, so that's my background.

   21. JRJoe Rogan1:53

       Now, what is your disagreement with Gary's position?

   22. SGStephan Guyenet1:57

       Everything. (laughs)

   23. JRJoe Rogan1:57

       Everything?

   24. SGStephan Guyenet1:58

       Yeah, so, uh-

   25. JRJoe Rogan1:59

       (laughs)

   26. SGStephan Guyenet1:59

       How about-

   27. JRJoe Rogan2:00

       Ask Gary.

   28. SGStephan Guyenet2:00

       ... how about I just-

   29. JRJoe Rogan2:02

       Mm-hmm, sure.

   30. SGStephan Guyenet2:02

       Can I start by explaining-
2. 3:24 – 7:34

   Stephan’s core thesis: the brain regulates fatness (car-and-driver analogy)

   1. JRJoe Rogan3:24

      (clears throat)

   2. SGStephan Guyenet3:24

      ... um, why the brain is important in obesity. So imagine you're an alien coming down from outer space, and you wanna 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 wanna 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.

   3. JRJoe Rogan4:03

      (clears throat)

   4. SGStephan Guyenet4:04

      Now, why is that? The reason is that you're studying the wrong part of the system. If you wanna understand the, uh, 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 s- the speed of the car. The thing that regulates the size of fat cells is the brain. So let's talk about, um... 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 wanna talk about. And all these circuits evolved, and these are non-conscious, by the way. So you don't decide you wanna be hungry. You don't decide that you wanna have a craving. These are things that bubble up from non-conscious parts of your brain that you don't control. So, um, these circuits are calibrated to an environment of our ancestors, not the environment we're li- we're living in right now. So these circuits all evolved to function optimally in the environment of our ancestors, prov- promote the survival and reproduction of our ancestors-So, um, 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 overconsume, and they push our bodies to accumulate and hold onto 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, um, and so let's get into that. Let's talk about what some of the evidence is that

3. 7:34 – 12:03

   Evidence claims for a brain-centric model: genetics, drugs, leptin pathway

   1. SGStephan Guyenet7:34

      supports this idea that I've just laid out. So I wanna start with, um, the genetics of obesity, and I think this offers some-

   2. GTGary Taubes7:42

      But can we... (clears throat) Can I interrupt for one second?

   3. SGStephan Guyenet7:44

      Uh, as long as it's very brief.

   4. GTGary Taubes7:46

      Just a question. I don't, I still don't quite understand what the model is.

   5. SGStephan Guyenet7:50

      Okay, how about, how about this?

   6. GTGary Taubes7:51

      I mean, I understand the dysregulation-

   7. SGStephan Guyenet7:52

      How about, how about-

   8. GTGary Taubes7:52

      ... of the brain with environment, but-

   9. SGStephan Guyenet7:53

      If, 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, uh, continuing.

   10. GTGary Taubes8:02

       Okay.

   11. SGStephan Guyenet8:02

       So let me, let me just finish. Um, 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, the, the most interesting studies are the genome-wide association studies. They get hundreds of thousands of people together, and they, um, sequence or they, 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 talk, by talking about height genes. So height has a strong genetic component, so does body fatness. Um, and researchers has 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? 'Cause growth of the skeleton determines your height. So genes that determine diabetes risk, type two diabetes, are all about insulin sensitivity, all about insulin secretion and the function of the, uh, 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, um, 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, um, 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... Leptin, um, 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, um, 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. Um, we've

4. 12:03 – 19:37

   Most fattening diet argument: junk food and ‘palatability’ vs single nutrients

   1. SGStephan Guyenet12:03

      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, um...... basically, there are three different ways that I'm gonna look at this from. Um, but first I wanna say that the... 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-

   2. JRJoe Rogan12:38

      (clears throat)

   3. SGStephan Guyenet12:38

      ... it's human junk food. In a variety of non-human species and humans, it's human junk food that is more fattening than any others. And I'm gonna skip over some of the research here-

   4. JRJoe Rogan12:49

      (clears throat)

   5. SGStephan Guyenet12:49

      ... um, 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, um, 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, um, I'm gonna, I'm gonna gloss over some of the individual research 'cause I'm being long-winded here. But, um, essentially what you find is that this s- stuff is really fattening in animals, many different species, it's super fattening in humans, calorie dense. When you put, create an environment with abundant, easy, calorie-dense, tasty foods rich i- carbs and fat, you see this dramatic overconsumption in 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.

   6. JRJoe Rogan14:01

      (clears throat)

   7. SGStephan Guyenet14:01

      You can't replicate it in animals. You can't replicate it in humans.

   8. JRJoe Rogan14:05

      Well, when you say you can't replicate it, you mean you can't replicate obesity? What do you mean?

   9. SGStephan Guyenet14:09

      Yeah, um, that's right. You cannot, 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, we can get deeper in this if you want.

   10. JRJoe Rogan14:37

       But I, I'm confused.

   11. SGStephan Guyenet14:38

       Yeah.

   12. JRJoe Rogan14:38

       So, you're, you're saying that the, the diet that causes the most obesity is what we think, right? This, uh, human junk food diet-

   13. SGStephan Guyenet14:46

       Correct.

   14. JRJoe Rogan14:46

       ... rich in sugar, simple carbs, bullshit, bullshit diet, right? Y- what are you... You're saying that you can't replicate that with just sugar and carbs?

   15. SGStephan Guyenet14:56

       You cannot fully replicate it.

   16. JRJoe Rogan14:57

       Fully, in what sense?

   17. SGStephan Guyenet14:57

       So, it's... What I mean is that if you just feed... if you just increase sugar intake-

   18. JRJoe Rogan15:04

       Right.

   19. SGStephan Guyenet15:04

       ... 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-

   20. JRJoe Rogan15:19

       Tha- that's very confusing. So-

   21. SGStephan Guyenet15:21

       How's that?

   22. JRJoe Rogan15:22

       Because I'm, I'm not sure exactly what you're saying. You're saying you... 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?

   23. SGStephan Guyenet15:38

       Um, so (clears throat) what I'm saying is that if you, if you give people or animals the, uh, the actual human junk food-

   24. JRJoe Rogan15:47

       Right.

   25. SGStephan Guyenet15:47

       ... with all the carbs and fat and everything-

   26. JRJoe Rogan15:50

       Mm-hmm.

   27. SGStephan Guyenet15:50

       ... 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, like, fully explain why those foods are fattening.

   28. JRJoe Rogan16:07

       See, this is where I'm confused.

   29. SGStephan Guyenet16:08

       You see what I'm saying?

   30. JRJoe Rogan16:08

       No, I don't see what you're saying.
5. 19:37 – 27:41

   Gary’s counter-model: fat accumulation driven by hormonal regulation (not willpower)

   1. GTGary Taubes19:37

      So I took off my hearing aids, and it'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, and I, I... My first two books were studying what's called pathological science, which is about people who got the wrong results in science, 'cause a lot of times scientists do. So my- I'm very sensitive to this, and as I was doing the research for my first book, which took five years, what I noticed in- 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 gonna use some socially unacceptable, uh, language, 'cause in part that's how they thought about it. In fact, when you read the, uh, 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, they're... But it- but it was all brain centric.

   2. SGStephan Guyenet20:46

      Mm-hmm.

   3. GTGary Taubes20:47

      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 the- they got the wives to stop having sex with the husbands if they didn't lose weight every week-

   4. SGStephan Guyenet21:03

      Hmm.

   5. GTGary Taubes21:04

      ... and that would motivate them. I think even you point out that sex is a greater motivator in your book than tasty foods.

   6. SGStephan Guyenet21:11

      (laughs) I didn't say-

   7. GTGary Taubes21:12

      It didn't work.

   8. SGStephan Guyenet21:12

      ... it was greater, but I said it was on par, yeah.

   9. GTGary Taubes21:15

      On par. So a- and I'm gonna just read you, uh... I won't read you that. The- so there was this... While the obesity research community is focusing on the brain, there were people studying fat metabolism. Uh, endocrinologists, they study hormones and hormone-related disorders, saying that the o- you know, fat storage 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 it well. And our body does a very careful job of deci- 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 disorder 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, they're gonna... their behavior is gonna respond. They'll be hungrier, they'll eat more, they'll be gluttons, all these things. So it was a switching the, the causality. Instead of the brain determining energy balance and that determining fat accumulation, the idea was, uh, sort of, "Let's see what regulates fat accumulation." If that's dysregulated, if I have a- if I give birth to a daughter who weighs 100 pounds at age four, I'm not gonna worry about how much she eats and exercises, I'm gonna worry about what's going on with fat accumulation and this young girl, that her body is... Just as if you give a- you know, if you have a, a child who's six foot eight when he's six years old, you're not gonna worry about how much he eats and exercises, you're gonna 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, uh, 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 pre- be predetermined, you know, be driven to be fat.

   10. SGStephan Guyenet24:13

       Mm-hmm.

   11. GTGary Taubes24:14

       So for example, when I was in high school, 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.

   12. JRJoe Rogan24:38

       Mm-hmm.

   13. GTGary Taubes24:38

       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. Um, 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 that. I don't think about what the problem is with her brain regulating intake and expenditure. I think about what's, why is her body driving her to be 300 pounds? So that's, I think, kind of the fundamental difference. Um, and is it, 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?

   14. JRJoe Rogan25:33

       Yeah, is this a reductionist perspective? 'Cause I mean, i- i- isn't it a holis- 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 l- is seems-

   15. GTGary Taubes25:45

       I'm not saying it's separate.

   16. JRJoe Rogan25:46

       Right.

   17. GTGary Taubes25:46

       The question is, is the brain driving what's happening in the body or is it responding to what's happening in the body?

   18. SGStephan Guyenet25:51

       Yeah, so-

   19. JRJoe Rogan25:51

       Mm-hmm.

   20. SGStephan Guyenet25:52

       Um, and you know, 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. Um, 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 o- than others, and we also know what the genes do that underlie those differences.

   21. GTGary Taubes26:32

       No, no, w- wait, wait. Let me-

   22. SGStephan Guyenet26:33

       And they are primar- I'm not done, Gary. Let me finish.

   23. GTGary Taubes26:35

       I just wanna read something-

   24. SGStephan Guyenet26:35

       Those genes-

   25. GTGary Taubes26:36

       ... from your book.

   26. SGStephan Guyenet26:36

       Those genes-

   27. GTGary Taubes26:37

       Can I read something from it?

   28. SGStephan Guyenet26:38

       No, nope.

   29. GTGary Taubes26:38

       Okay.

   30. SGStephan Guyenet26:38

       Not right now. I'm, I'm in the middle of saying something. Those genes are, um, 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.
6. 27:41 – 41:34

   Genes, effect sizes, and where they act: brain vs peripheral tissues

   1. GTGary Taubes27:41

      One hypothesis is my body... And this is what Stephan has talked about. So I wanna... Just the thing I wanted to read, how much... I'll ask you the question. How much of the, the variation in human obesity do those genes explain?

   2. SGStephan Guyenet27:56

      So if you look at the genetics of-

   3. GTGary Taubes27:59

      No, I didn't ask how much g- is genetic.

   4. JRJoe Rogan28:01

      Gary, I'm answering your question.

   5. SGStephan Guyenet28:02

      Look, once he starts talking-

   6. JRJoe Rogan28:03

      You need to let me-

   7. SGStephan Guyenet28:04

      Yeah, please, Gary. Um, 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.

   8. GTGary Taubes28:50

      How much?

   9. SGStephan Guyenet28:52

      It's like, uh, right now, I think it's up to about 10%.

   10. GTGary Taubes28:55

       It was 3% when your book was published.

   11. SGStephan Guyenet28:57

       Yeah, that's correct.

   12. GTGary Taubes28:58

       So you're saying they did 7%?

   13. SGStephan Guyenet28:59

       Absolutely, yeah. The latest... Yeah, actually let me cite the, uh, the study there.

   14. GTGary Taubes29:04

       S- so, while, while Stephan s-

   15. SGStephan Guyenet29:04

       No, just a second. I'm gonna cite the study. Just a second. I'm gonna cite the study. Uh, the study is under reference number two. So you can, 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, and 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.

   16. JRJoe Rogan29:57

       I am.

   17. GTGary Taubes29:58

       And I was.

   18. JRJoe Rogan29:59

       And how are you surprised? Do you-

   19. GTGary Taubes30:00

       Well, again, I-

   20. JRJoe Rogan30:00

       What do you disagree with?

   21. GTGary Taubes30:02

       Well, virtually everything, but, um, let's begin with... I have to track back now. The, um, okay, so drugs that explain obesity, 10%. Well, the argument that I was making and the argument I continue to make, i- imagine if, you know, take Stephan's, uh, car metaphor.

   22. JRJoe Rogan30:22

       You see Stephan, he says Stefan.

   23. GTGary Taubes30:24

       Okay, sorry.

   24. JRJoe Rogan30:24

       You say Stefan, right?

   25. SGStephan Guyenet30:25

       It's okay.

   26. JRJoe Rogan30:25

       Stefan.

   27. SGStephan Guyenet30:25

       I'm not offended.

   28. JRJoe Rogan30:26

       That's okay.

   29. GTGary Taubes30:26

       But I mean-

   30. SGStephan Guyenet30:27

       I apologize.
7. 41:34 – 46:06

   Leptin deep dive: thermostat/set point and site-of-action dispute

   1. JRJoe Rogan41:34

      Um, leptin is produced where?

   2. SGStephan Guyenet41:36

      Yeah, leptin is produced... Yeah, let's talk about leptin a little bit. It's produced in fat cells, um, 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 a negative feedback loop, um, which is a really simple engineering term that works like a thermostat. So with your thermostat, you, uh, 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, AC comes on, or the heat comes on to bring it up. That's called a 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, your thermostat measures temperature by using a thermostat, uh, 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, 'cause your brain is like, "No, I don't wanna be losing fat." And it makes you hungrier. It increases your cravings-

   3. JRJoe Rogan43:05

      Can I pause there?

   4. SGStephan Guyenet43:05

      Yeah. Sure.

   5. JRJoe Rogan43:05

      Is that, is that at a certain level of body fat? Is that at a s-

   6. SGStephan Guyenet43:08

      Um, so here's the-

   7. JRJoe Rogan43:09

      Is this just when you're losing body fat in general, like even if you're-

   8. SGStephan Guyenet43:11

      Yeah.

   9. JRJoe Rogan43:11

      ... a large person that's overweight?

   10. SGStephan Guyenet43:13

       Correct.

   11. JRJoe Rogan43:13

       When you're losing body fat in general, your body, it- it exacerbates-

   12. SGStephan Guyenet43:17

       Yeah.

   13. JRJoe Rogan43:17

       ... your hunger?

   14. SGStephan Guyenet43:18

       And this is, this is the thing that's really important to understand about obesity, um, 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.

   15. JRJoe Rogan43:37

       Mm.

   16. SGStephan Guyenet43:37

       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-

   17. JRJoe Rogan43:53

       So it'd be-

   18. SGStephan Guyenet43:53

       ... and their metabolic rate drops.

   19. JRJoe Rogan43:55

       So it'd be an evolutionary mechanism to force you to seek food.

   20. SGStephan Guyenet43:58

       Correct. And not just to force you to seek food. That's the main thing, but it also slows your metabolic rate.

   21. JRJoe Rogan44:03

       Mm.

   22. SGStephan Guyenet44:04

       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.

   23. JRJoe Rogan44:10

       Can I pause here?

   24. SGStephan Guyenet44:11

       Yeah.

   25. JRJoe Rogan44:11

       So when you're eating a sugary diet, a high, a high-calorie diet, you will produce more fat. Your body will get fatter, right? Is this correct?

   26. SGStephan Guyenet44:20

       Um, it depends on how many calories you're eating.

   27. JRJoe Rogan44:22

       Okay. If you're overeating, you're-

   28. SGStephan Guyenet44:23

       Yeah.

   29. JRJoe Rogan44:24

       ... you're consuming a lot of sugar, a lot of carbohydrates, your body will get fatter.

   30. SGStephan Guyenet44:27

       Correct.
8. 46:06 – 1:03:14

   Dual burden paradox: obese mothers with malnourished children

   1. GTGary Taubes46:06

      But one of the problems I... So the way I think you should think about this, you have a hypothesis, and, and this is the fundamental thing. Is obesity caused by overeating? 'Cause we know if you're getting fatter, you're storing more calories in your expend. That's just the, you know, that's 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's getting crowded. It doesn't tell you why the f- 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 what I... One of the questions I asked Stefan eight years ago, and it keeps coming up, is if we're gonna 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 a sort of Science 101, right?

   2. JRJoe Rogan47:07

      Mm-hmm.

   3. GTGary Taubes47:08

      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 the Pima living in Arizona. And observers saying these people are poor, they're malnourished, they're suffering through famines. They'd 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, uh, 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, uh, 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, um, I actually rarely do that in my books because you can find studies that will say anything.

   4. JRJoe Rogan48:13

      (laughs)

   5. GTGary Taubes48:14

      And you'll see in the studies, um, people misinterpreting them.

   6. JRJoe Rogan48:20

      What was the cause of the population of women to be o- obese in this?

   7. GTGary Taubes48:23

      Well, so one thing that happened during the fa- beginning in the 1860s, the Pima were put on a reserv- well, they moved onto a reserv- 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, uh, o- 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, y- 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, 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, Stefan 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, 'cause 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 this, these foods that travel with Western populations? And so, the exist- the ability ... And today, if you look up, uh, 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. See, 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 'cause 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, you know, and this was the first thing that I think we thought about back then, and it's still, if you can find populations with, uh, obesity epidemics, but without the modern food system, without Snackwell's and without Lay's potato chips-

   8. JRJoe Rogan51:09

      Mm-hmm.

   9. GTGary Taubes51:11

      ... um, and if you know that they're going through a famine or you know that the kids at least aren't getting enough food,-

   10. JRJoe Rogan51:17

       Mm-hmm.

   11. GTGary Taubes51:17

       ... how do you explain obesity in the mothers without assuming that the mothers are overeating?

   12. JRJoe Rogan51:22

       L- let's pause right there. Y- Stefan, is there a population of people that are obese that are not eating a Western diet, that are not eating sugary foods?

   13. SGStephan Guyenet51:33

       Um, that are obese and that are not eating sugary foods, probably not, because generally, once you have an industrialized food system, that's gonna 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-

   14. GTGary Taubes51:51

       Oh, can you-

   15. JRJoe Rogan51:51

       ... let's talk about the Pima first.

   16. GTGary Taubes51:51

       ... can you go back to the ... Yeah, okay.

   17. SGStephan Guyenet51:53

       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, um, originally the, they were agriculturalists. They were eating traditionally a very high carbohydrate diet based on unrefined carbohydrates. Originally, it was corn, beans, and squash primarily.

   18. GTGary Taubes52:19

       They were hunter-gatherers-

   19. SGStephan Guyenet52:20

       Um-

   20. GTGary Taubes52:20

       ... and agriculturalists.

   21. JRJoe Rogan52:21

       They were hunters-

   22. SGStephan Guyenet52:21

       They were primarily ... Gary, okay.

   23. GTGary Taubes52:24

       Go ahead.

   24. SGStephan Guyenet52:24

       They were primarily eating agricultural foods. They were also collecting some wild foods. That's correct. Um, they were fishing and eating mesquite pods, primarily agricultural. And, um, data are very clear on that, Gary. So-

   25. GTGary Taubes52:40

       No, no, no, n- yeah.

   26. JRJoe Rogan52:41

       (laughs)

   27. SGStephan Guyenet52:41

       Yes, they are. Uh, look, we have data-

   28. GTGary Taubes52:43

       We, we can't say things like that, Stefan-

   29. SGStephan Guyenet52:45

       (laughs)

   30. GTGary Taubes52:45

       ... 'cause we're gonna disagree-
9. 1:03:14 – 1:09:39

   Metabolic-ward overfeeding test: carbs vs fat at equal calorie surplus

   1. SGStephan Guyenet1:03:14

      diets in which calories were the same, but carbohydrate and fat intake differed. And the ones that I really wanna focus on right now that I think are key here are the studies where they increased calorie intake. So they fed people, they, they f... one study in particular, and, um, let's see, I'm gonna give you a number here. Um, let me see if I can give you a number here. Sorry.

   2. GTGary Taubes1:03:41

      While you look at that, um, can we, uh, bring up another issue? 'Cause what we're talking about ultimately is why people get fat.

   3. SGStephan Guyenet1:03:48

      Okay, I, I don't, I don't wanna divert here. I'm in the middle of something. So, um, now if we wanna understand why people get fat, we can look at studies that overfed people on fat or carbohydrate exclusively. So there's one study, um, the first one that I wanna talk about, first they figured out peoples' baseline calorie intake, figure out wh- 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, okay?

   4. GTGary Taubes1:04:21

      Which study was this?

   5. SGStephan Guyenet1:04:22

      This is Horton.

   6. GTGary Taubes1:04:23

      Okay.

   7. SGStephan Guyenet1:04:24

      Um, and-

   8. GTGary Taubes1:04:25

      Give me a sec, and when you're done-

   9. SGStephan Guyenet1:04:25

      Yeah, so number 16, number 16. So, um, 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? Now, these were very rigorous studies. I wanna emphasize that.

   10. JRJoe Rogan1:04:46

       Can I pause here?

   11. SGStephan Guyenet1:04:47

       Yeah.

   12. JRJoe Rogan1:04:47

       Did they monitor the, the actual calories they got?

   13. SGStephan Guyenet1:04:51

       Correct, yeah. So they were-

   14. JRJoe Rogan1:04:52

       So, they-

   15. SGStephan Guyenet1:04:52

       They were... go ahead.

   16. JRJoe Rogan1:04:53

       They, they had a baseline?

   17. SGStephan Guyenet1:04:54

       Yeah.

   18. GTGary Taubes1:04:54

       They used prisoners-

   19. JRJoe Rogan1:04:55

       But they-

   20. GTGary Taubes1:04:55

       ... in the Vermont State Prison.

   21. SGStephan Guyenet1:04:57

       Uh, no that's incorrect.

   22. JRJoe Rogan1:04:58

       But hold on sec-

   23. SGStephan Guyenet1:04:58

       This is a different study.

   24. JRJoe Rogan1:04:59

       So they, they had a baseline, and did they require them to maintain the same diet and then add additional fat or additional carbohydrates?

   25. SGStephan Guyenet1:05:07

       Yes.

   26. JRJoe Rogan1:05:08

       Yeah.

   27. SGStephan Guyenet1:05:08

       So same diet-

   28. JRJoe Rogan1:05:09

       So they studied the same foods?

   29. SGStephan Guyenet1:05:10

       ... and then they just bumped it up with fat or bumped it-

   30. GTGary Taubes1:05:12

       Wait, wait, wait.
10. 1:09:39 – 1:27:11

    The ‘10 calories per day’ argument and escalating tone

    1. GTGary Taubes1:09:39

       Um, the point that we keep getting away from that I haven't had an opportunity to, um ... 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, uh, f- 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, you know, 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? 'Cause 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, it tends to happen quickly in their 20s. Um, so we're asking this question. How do we ... If f- you've got a situation where we have to end up with 10 calories stuck in the fat cells every day, that's, uh, 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, when they'll en- ... Um, 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 gonna 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. Um, so those are ... That's ... When we're talking about this, like this question, could somebody get fat during a famine? Or can they stay fat during a famine? All they have to do is hold onto 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 th- 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 le- ... And again, uh, animal experiments of which there are probably hundreds by now, different animal models, you can disassociate obesity from hype- from eating too much in the animals.

    2. JRJoe Rogan1:12:59

       Can I pause you for a second?

    3. GTGary Taubes1:13:00

       Yeah.

    4. JRJoe Rogan1:13:00

       Y- so, uh, essentially you're saying that even if someone is taking in, uh, uh, uh, a good amount of calories, like, uh, a s- 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, uh, vegetables and things along those lines, your body would not do that.

    5. GTGary Taubes1:13:30

       Well, so this is, uh, gets to the mechanism question-

    6. JRJoe Rogan1:13:33

       Yes.

    7. GTGary Taubes1:13:33

       ... and the evidence question.

    8. JRJoe Rogan1:13:34

       So but, but you're saying that, right?

    9. GTGary Taubes1:13:36

       Yeah.

    10. JRJoe Rogan1:13:36

        So you're saying that if, 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 2,000 calories of milkshakes and, uh, you know, sugary drinks and p- pasta and bullshit, that that person is going to gain a certain amount of calories and just put them to fat-

    11. GTGary Taubes1:13:58

        Right.

    12. JRJoe Rogan1:13:58

        ... regardless.

    13. GTGary Taubes1:13:59

        That's ... Yeah. That's the hypothesis.

    14. JRJoe Rogan1:14:01

        Same-

    15. GTGary Taubes1:14:01

        And that hypothesis-

    16. JRJoe Rogan1:14:02

        ... same activity?

    17. GTGary Taubes1:14:02

        This being a science, that hypothesis can be tested.

    18. JRJoe Rogan1:14:05

        Yes.

    19. GTGary Taubes1:14:05

        And, uh, Stefan thinks it's been tested 80 times, a dozen times-

    20. JRJoe Rogan1:14:09

        So, Stefan, your-

    21. GTGary Taubes1:14:10

        ... I think it's, 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.

    22. JRJoe Rogan1:14:22

        From your perspective, this is not the case. Your perspective is that, like, uh, as you were saying, in the study where they c- closely monitored these people's diets, and they added additional fat and a- a- additional carbohydrates, that they both gained-

    23. GTGary Taubes1:14:34

        Yeah.

    24. JRJoe Rogan1:14:34

        ... the same additional amount of weight.

    25. GTGary Taubes1:14:36

        Yeah, that's right. I mean, if Gary's hypothesis-

    26. JRJoe Rogan1:14:38

        But is this a short term?

    27. GTGary Taubes1:14:38

        ... is correct, you have to see different levels of fat gain. I mean, Gary's-

    28. JRJoe Rogan1:14:41

        Was this a short term study that they did?

    29. GTGary Taubes1:14:43

        Yeah, it was short term.

    30. JRJoe Rogan1:14:43

        How, how short term was it?

Episode duration: 2:37:41