The Checkup with Doctor Mike - How RFK Jr. Manipulates Nutrition Research | Kevin Hall

Episode Date: August 31, 2025

Huge thanks to Kevin Hall for being so transparent in this interview. Check out his new book "Food Intelligence" now: https://www.penguinrandomhouse.com/books/671334/food-intelligence-by-julia-belluz-and-kevin-hall-phd/Check out his website here: http://kevinhallphd.com/I'll teach you how to become the media's go-to expert in your field. Enroll in The Professional's Media Academy now: https://www.professionalsmediaacademy.com/00:00 Intro02:22 Physics Over Nutrition17:01 Macros vs. Fat Loss29:50 Low Carb Diets38:11 Unexpected Changes41:02 Ketogenic Diet vs. Childhood Seizures42:55 The Biggest Loser Study1:13:35 Ultra-processed Foods1:33:20 High Performing Athletes1:35:27 Calories In/Out vs. CIM Model1:52:30 Ultra-processed foods mechanisms1:57:35 His Battle Against RFK Jr.2:15:30 RFK Jr. Censoring ResearchHelp us continue the fight against medical misinformation and change the world through charity by becoming a Doctor Mike Resident on Patreon where every month I donate 100% of the proceeds to the charity, organization, or cause of your choice! Residents get access to bonus content, an exclusive discord community, and many other perks for just $10 a month. Become a Resident today:https://www.patreon.com/doctormikeLet’s connect:IG: https://go.doctormikemedia.com/instagram/DMinstagramTwitter: https://go.doctormikemedia.com/twitter/DMTwitterFB: https://go.doctormikemedia.com/facebook/DMFacebookTikTok: https://go.doctormikemedia.com/tiktok/DMTikTokReddit: https://go.doctormikemedia.com/reddit/DMRedditContact Email: [e-mail] Producer: Doctor MikeProduction Director and Editor: Dan OwensManaging Editor and Producer: Sam BowersEditor and Designer: Caroline WeigumEditor: Juan Carlos Zuniga* Select photos/videos provided by Getty Images *** The information in this video is not intended nor implied to be a substitute for professional medical advice, diagnosis or treatment. All content, including text, graphics, images, and information, contained in this video is for general information purposes only and does not replace a consultation with your own doctor/health professional **

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Secretary Kennedy has this Maha movement, make America healthy again, frequently targeting ultra-processed foods. If I'm truly wanting to solve all those problems, like I would be calling you every day to try and solve these problems. Is that happening? No, not at all. In our health lead, a top researcher for the National Institutes of Health shocked the scientific and medical communities this week

by announcing his early retirement and blaming it on censorship from RFK Jr.'s administration. I was really excited about this piece of research, we were addressing the question about whether or not ultra-processed foods high in fat and sugar can cause the same kind of changes in the brain's dopamine response as highly addictive drugs. And they didn't seem to have the effect that many addictive drugs do. This narrative that...

It's as addictive as crack. That doesn't seem to be at work here. We had a reporter asked for an interview to discuss the findings of that paper for a piece that she was writing in the New York Times. And that interview was denied. Not only were we not able to give talks, not only were we not able to publish our papers in the normal way, but now they're manipulating the way that we communicate our results to the public.

That's a huge problem. If the premier biomedical research organization in the world is no longer interested in communicating science. Welcome to the Checkup podcast. Today's guest is Goat Tier in Nutrition Science, Kevin Hall, Ph.D., one of the top metabolism researchers in the country. His gold standard inpatient studies have changed how we think about diets,

especially ultra-processed foods, appetite, and weight loss. He's also the guy behind the biggest loser follow-up study that cut through so much diet hype with actual data. His new book, Food Intelligence, translates decades of studies into practical advice on metabolism, diet myths, and when to ignore the diet tribes on source. social media. You'll hear us tackle calories in versus calories out, how to spot good

versus bad nutrition advice, and why he recently left NIH, and why despite public promises by RFK Jr. around investing in nutrition and obesity research, the reality was that of censorship and corruption at the highest levels. It's honest, evidence-based, and incredibly valuable. With MX Platinum, access to exclusive MX pre-sale tickets can score you a spot trackside. So being a fan for life turns into the trip of a lifetime. That's the powerful backing of Amex. Pre-sale tickets for future events

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I've had misinformation nutrition experts on the channel. But I've never had someone of your caliber because you're really the top-tier goat-level nutrition expert that I think one could have on a show. So I appreciate you making the time to come here and talk with us about it. I appreciate those superlative introductions, especially given that my background in PhDs in physics, not in nutrition. So it's a little bizarre to be spoken of that way. Well, I think the contribution that you've made to the field of nutrition research is immense because when people like me, I'm a family medicine doctor, when I need to figure out what

to tell patients, it comes from the work you've done. In fact, when we think about the current state of health care in the United States, the Maha movement, and the things that they're talking about with chronic health diseases, if we want to fix those things, we need to look at the work you've done and we need to fund more work for you to do. And we're obviously going to get into that. But if you want to tell the audience of how you got to your degree, which seems unrelated to the work you were doing in metabolic research. How did you get there? Yeah, I mean, it's a bit of a long story. I'll try to shorten it as much as possible. This is the beauty of the podcast. Okay, great. Nuance is king here. I mean, one of the things that's really interesting to be described in that way

as a nutrition expert is I don't still see myself that way. Interesting. Because I've listened to folks on your show and friends of mine like Kevin Klat, who's his entire background is in nutritional science and dietetics. And he has such a wealth of knowledge that I learned so much from these folks still to this day. And I know that there's huge gaping holes in my knowledge. And I kind of hope I know where those are so I can not look like a fool talking about those particular areas. But that's what makes you an expert. A lot of people think expertise comes from an immense amount of knowledge. To me, I think it comes from immense knowledge of what you don't know. It's both, right? I mean, I think you have to know what you don't know. And you also have to

know with relative degrees of certainty and uncertainty about what we do know quite well, what we're still going to be surprised about in the future. We think we have a pretty good handle on something and it turns out, oh, that was wrong. I kind of messed up with that. And then there's always going to be some things that we think we have a really good handle on. It's going to take a lot to shake us out of our beliefs, but we should still be open to being wrong about those kinds of things and knowing the standard of evidence that's going to be required to do that. So, So, yeah, so back up of how I got interested in this. You know, I wanted to be a physicist.

I wanted to be, you know, one of these hardcore particle physicists, theoretical physicists. I was always, like, fascinated by, you know, why is anything exist? You know, why do we have matter? Why is it not mostly anti-matter as opposed to the normal kind of matter? All these, like, big questions that, you know, a high school student might have in their later years of high school. And I enrolled in a physics program and was doing pretty well. well. But there was almost this one guy who was always at the top of the class. And this was just easy for him. Right. I mean, for me, I was pretty easy for the most part until like the final year of my undergraduate physics degree where I realized, you know, I was pretty good at mathematics. But this guy had no challenges in math. I mean, not quite goodwill hunting level. It's funny. That's the comparison. That's where my head was also. I could see. But, but, you know, I sort of came to the realization that, you know, I could back.

my head against the wall for the next, you know, 40 years of my career and probably make a decent living? Or should I start to look around and see, you know, maybe those dreams weren't really for me? Could I, could I, could I, was I better suited to do something else? And I happened to get a job over a summer in a physiology lab. And I was doing some electrophysiology experiments with smooth muscle cells. And I started reading about these kind of very old papers by Hodgkin and Huxley back in the 1950. who were building mathematical models of how nerve cells were firing, like what was going on with respect to the action potentials,

how do nerve cells fire? Can we actually build a mathematical model of that? And I got really interested in this. Maybe this is kind of the sweet spot because there's something really interesting from a biological perspective. You could apply math to it. And fortunately, and this is in Canada, I'm Canadian originally, and there's this really interesting program at McGill University

called the Center for Non-Linear Dynamics and Physiology and Medicine. Okay. So non-linear dynamics is basically what a lot of people think of as chaos theory. Like that's where it got really popular for a brief spurt in like the early 90s or so. And this, it was basically a group of mathematicians, chemists, physicists, working in the physiology department. And they were trying to apply mathematical methods to understand abnormal heart rhythms, for example. And that's kind of what I did my PhD on.

I was interested in cardiac arrhythmias and trying to develop ways to diagnose one versus another was something an ectopic foci focus in the heart, or was it more of a reentrant loop? How could you tell that with a limited number of electrodes as the cardiac electrophysiologists were doing at the time? A lot of access diagnoses. Yeah, yeah, and trying to use the geometry of the heart and how waves propagate to kind of figure out what was going on. Now we have like these amazing mapping technologies that people can use to kind of really.

target where to ablate or burn pieces of heart, heart tissue. But back then, it was like you had like one little catheter with maybe four electrodes on it and you were just trying to figure out where it was, right? And so I was kind of trying to mathematically model this and come up with some useful algorithms. We actually started to file a patent about this, about how to kind of locate these different abnormal regions of the heart. And then we dropped it because my supervisor I'm a theorist. I don't want to deal with these patent things. And I think something got sold from a Stanford group many years later for like a hundred million dollar piece of technology that was like, man, if I just pursued that. But yeah, so it was a fun sort of

place to be. And there was a kind of a critical mass of folks who were doing this kind of work. but they had kind of done something which was really interesting. I never really thought of this before. The cardiologists weren't paying any attention to them. So they were building these mathematical models, and we published a couple papers in cardiac electrophysiology journals, but hardly anyone ever cites them. They're too mathematical for most of the folks reading those journals.

We weren't doing great SciCom back then on how to kind of translate these results to these folks. And yet they'd formed a critical mass of folks in the field that could then publish their own stuff over and over again, get grants to kind of do this kind of work. But they were having very, very little impact. And I thought, yeah, I don't want to do that. I want to do something that's actually going to be picked up by more people and maybe have an impact on improving the lives of folks. And so I was kind of in this weird disillusionment state at the end of my Ph.D. program. And a group of folks had come up to take a summer course that the institute was offering. I was teaching part of it.

And they were also recruiting folks to come to the San Francisco Bay Area to join this little biotech startup called Intelos. And I was, I think, employee number 14 or something like that. So it was early days. And they said to me, what we're doing is we're building computer simulation models of different disease types in coordination with, in coordination with, pharmaceutical partners. And we've decided that you're going to be in charge of our type two diabetes program. I'm like, okay, that's cool. What's diabetes? No clue, right? They said, don't worry about it. We're also hiring like a life science person who's going to work with you and you're going to have many meetings with the folks at Johnson and Johnson, who is the pharmaceutical development

partner. And yeah, that's where I started learning about endocrinology and metabolism and, you know, what happens to the food once we eat it in terms of carbs, fat, and protein, how do they interact in our bodies, how the different organs communicate with each other through hormones and metabolic fluxes and trying to then simulate that knowledge in a computer simulation, and not just in diabetes, but in the normal physiology as well. In other words, what do you have to do to do to the normal physiology to create, first of all, a normal simulation in normal physiology? What do you have to do to kind of make a realistic simulation of people of varying degrees of insulin resistance, of varying degrees of impaired glucose tolerance, and how does that progress over

time? It was a huge challenge. And I mean, we had some success. The company's no longer existence. So in that sense, it wasn't that successful. But this kind of area of research has kind of been absorbed into different pharmaceutical companies now. They do some of the stuff in-house. But that was just a fascinating area. And I just sort of realized, this is kind of my wheelhouse now. I have a sort of gut feel for how this system works. And I didn't feel like I was bashing my head against the wall as hard as it was. And I knew that there was certainly limits to not just my knowledge, but knowledge overall in this field. I felt like, you know, this was something I could make a difference. I could actually better understand this. So when I

saw that the business model of this company was kind of not working out. I was starting to think about, okay, where can I go and continue this kind of work? And right around then, the NIH was recruiting folks for a new lab that was, again, trying to recapitulate this idea of bringing people with quantitative training together to work on biological problems. And so I started a tenure track position at NIH, and I was there for 21 years. What was the timeframe that that was happening? It was 2003. Okay. I joined the NIH. And initially, I was just doing this computer simulation modeling again, now looking more at obesity and looking at kind of longer time scales about what happens to people's body composition as they gain and lose weight. How does

their metabolism slow down or speed up? You know, how do we swap out nutrients like carbs and fat in the diet? How does protein play a role in those kinds of things? And I was kind of, this was also during the one of the many rises of low-carb diets. And so there was this idea at the time that a calorie is not a calorie, that, you know, low-carb diets have some sort of metabolic advantage. I'd read, you know, South Beach, Atkins. Yeah, Atkins book and picking these very, you know, interesting claims about this. And I thought, well, what is the model that we're building? What does it say? And we made certain predictions. And I remember I was giving me, my sort of mid-tenure review talk.

And I was talking about this model that I built and how we were making certain predictions of experiments that could be run at the metabolic unit that had opened, I think, in 2004 at the NIH Clinical Center. And I thought, you know, it would be great if we could get some of the clinicians to do these kinds of experiments. And so after the meeting wrapped up, the scientific director at the time of our institute said,

you know, that was really interesting. Why don't you do those experiments? What are you talking about? I have a physics PhD. I can't do this, right? And that was one of the really remarkable things at the time. The NIH was the kind of place where they didn't care that much about your background. If they thought that you had a really good idea and the motivation and the drive to actually

learn what was needed to actually do this, they would take a chance. And that was, you know, I don't think that there's many other places on the planet that would allow me to do that. And they supported me. They said, okay, well, we're going to teach you what an IRB is. We're going to teach you what a clinical trial looks like, how to write one, how to power a study. In other words, how do you determine the number of people that you would need in order to see the kind of effects that you're predicting in your model? And then what's sort of feasible, what's not feasible? And yeah, I sort of thought, they're only going to give me one chance to do this. And I roped in all these other folks from different institutes.

At that time, the too big to fail was kind of the buzzword at the time. I'm like, I'm going to make this too big to fail. But they can't stop this study. I've got like folks from the Addiction Institute involved. I've got folks from the Mental Health Institute. I've got like, you got the buy-in across the board. We're going to do this crazy study. And yeah, it was, it was, it took forever, right?

and I hired this very brave postdoc who'd done some human metabolic physiology studies in the past. I said, look, I've never done this before. I'm maybe relying on you like a ton. And I sort of realized it was just me and him and eventually we had like an undergraduate research assistant. I learned early on like I should not touch any of this equipment. I like no skills in that regard whatsoever. I just would like stand back. I'm like, I'll help explain the study to the patient. you know, we'll get their consent and, you know, I'll check in every once in a while. And even that was like, yeah, probably not a good idea for me to check in. My bedside manner is not necessarily the best. But, but, you know, these folks did just a remarkable job, but it took forever.

Like, we started that study in 2009. So that's when we got the protocol approved. We published the first paper on it in 2015. It was in 19 men and women with obesity. They stayed for a month in two, two-week blocks at the NIH clinical center where we manipulated their diet under super highly controlled circumstances, trying to see if the effects that our model was predicting turned out to be correct, or were some of the effects that were being propagated at the time about low-carb diets being, or carbohydrate-restricted diets having the kinds of effects that on metabolism that were expected, were those going to win out? And, yeah, it was a fun and frustrating time because we were running on a very small team doing this.

I'm curious, based on the models you were running, how were they comparing to existing knowledge at the time? Were they finding things that disagreed with common understanding in the space? Yeah, so it was really interesting. It's a bit of a yes or yes and no type of question. Yeah, what which would? Yeah, so the idea at the time, depending on who you were listening to, if you were listening to the folks in the low carb space, there was this idea that, this idea that a calories, a calorie, is nonsense, right? Because, you know, bodies aren't bomb calorimeters as people talk about bomb calorim is a way that you measure calorie content of food.

And we metabolize fuels very differently. And so to kind of translate what you see in a calorimeter to what you see in a human is like a leap of logic that many folks in the space were like, yeah, that's just nonsense. But there actually is a very long history of this where people actually discovered this idea that a calorie is a calorie from doing exactly those kinds of studies. We talked a little bit about it in the book of Max Rubner, this amazing German physiologist who basically he was doing these experiments on dogs where he was interested in how do you feed dogs to change the rate at which they lose body fat. And he found out that if you give dogs sugar, you have to give them twice as much sugar in grams as you have to give them in fat and oils to kind of slow the rate of body fat loss from starvation to the same extent. And that was a big mystery. Like, why is it that you need so much more carbs than you do fat in a gram basis to slow body fat loss to the same extent? And so he worked out the precise ratio.

And then he had a bob calerameter. And he, lo and behold, found out that, you know, fat has twice the number of calories per gram a little more than sugar. And it was the same sort of relationship. And so he's kind of put two and two together. It's not the grams that mattered. It's the number of calories that the food contains that mattered. And then he went on to show that, you know, in dogs, this idea of conservation of energy holds in dogs. And this, thus was born the idea of a calories, a calorie.

our models were showing that in humans or human models were showing that yeah it's really close to that but you could actually devise diets that would deviate from that rule very slightly very slightly like we're talking it's hard very difficult to measure and that's why we designed the study with such meticulous care to measure like every you know 0.1 gram of food that people were eating and making sure they were eating all the food so just to catch the audience up you were designing a study that was looking to see if you change the macronutrient content of food. So basically changing the amount of carbohydrates, proteins or fats, someone's consuming to see if changing the combination of those but keeping the calories the same would impact their ability to lose or gain weight. Body fat.

Or body fat specifically. Exactly. And Rubner, this guy from the, you know, I guess it was the 19th century, would say, yeah, no, a calorie is a calorie. We've worked that out. at the time there are folks saying, you know, no, low-carb diets are going to have an advantage, right? Because you've cut carbs in the diet, insulin levels go down that releases fat from fat cells,

you're going to burn more fat, and therefore you're going to lose more fat, whereas if you don't cut carbs and you just cut fat, for example, the same number of calories, but keep carbs and protein at baseline, then you're not going to get a change in insulin, and that's going to keep the fat in the fat cells. You're not going to change how much fat. Which is known as the CIM model. No, that's not quite, that's, yeah, the CIM model is a little bit different than that, but we can maybe talk about that. But in this case, it was just a question of reducing the carbs, does that have a preferential

effect to increase body fat loss as compared to reducing fat, regardless of whether or not it has to do with obesity, which is what the carbohydrate insulin model is about. Got it. And so our model simulated many of these physiological processes. But it said that for certain amounts of cutting of carbs versus cutting of fat, if you just cut one versus the other and you kept the other two macronutrients at baseline values to kind of maintain weight, that if you cut 30% of calories from carbs versus cutting 30% of calories from fat, on the same people in different occasions, the time when you cut fat in the diet would lead to a tiny, tiny little bit more fat loss. because the model made a weird prediction which said that the amount of fat that the body is burning shouldn't depend at all on the amount of fat that it's eating that's really weird right i mean it's like you cut a stick a butter out of your daily diet and your body doesn't bother to register

that you did that and it keeps burning the same amount of fat um there are folks that said you know there's no way that's going to happen what's going to happen is your body is going to adapt to the fuels that it's being provided and the amount of fat that's being burnt is going to go down and as a you're not going to lose as much fat. That was one prediction. When you were creating the model, the simulation here, you need to obviously set parameters and rules for it. What research were you kind of feeding into the model? How were you deciding what research to use? And did you feel that the model had any gaps in its knowledge? Oh, the model has huge gaps, right? And we're feeding into the best sort of previous studies. And what we had done is we'd looked at the study where we had

at overfeeding of fat or overfeeding of carbs. And in that case, the data suggested that, indeed, when you overfeed fat, nothing happens to the amount of fat that the body burns, at least in a relatively short-term basis. And that was kind of interesting. And we used that piece of information in the model. And I thought, I kind of suspected that wasn't going to be the case. So my sort of MO when designing experiment is, I'm happy to be wrong.

We're trying to do the null hypothesis. I would love to learn something that we didn't know before because the model makes a prediction based on what we previously knew. If the model's wrong, it means we're learning something new or I should have known it. Maybe it's not new. Maybe I just was too boneheaded to have known it read the right paper previously. But at least it has the potential of showing something new. Alternatively, if the model's right, and in this case it was suggesting that the proponents of low carb diets and the metabolic advantage of low, carb diets might not quite have it right, then that's also interesting. So I try to design experiments

so that no matter what the outcome is, it tells us something interesting, right? So then when you compared the research that was coming out of the simulation versus doing it in real life, what did you find? Well, I was a little disappointed that the model was right. Which, I mean, again, it's a good thing that, okay, we kind of knew enough going in to build a model that accurately predicted what was happening in these real people, not a real world situation by any structure in the metabolic world in this, yeah, and it's an incredibly tiny difference. So that what happened was, many of the things happened that the low carb folks have said, which is absolutely right. You cut carbs in the diet, insulin secretion goes down. You know, insulin is secreted by the beta cells of the

pancreas, roughly in proportioned how much glucose is around in the blood. And if you cut carbs, the glucose levels go down, insulin secretion goes down. And that's exactly what we saw. We also saw that we have these wonderful respiratory chambers where we can put people in and measure on a minute-to-minute basis how much oxygen they're consuming, how much carbon dioxide they're producing. And from that, we can calculate how much carbs they're burning, how much fat they're burning, how much protein is being used, and how many calories they're burning overall. And what we found was indeed exactly like many of the folks were talking about mechanisms of low-carb diets is that The insulin secretion goes down, free fatty acids go up in the blood, the fat cells are releasing more fat into the circulation, and you're burning more fat.

And that sort of seemed to plateau after that week or so that we put these folks on the diet. And therefore, because the fat intake didn't change, right, you only cut carbs, fat oxidation goes up, you're burning fat, you lose body fat. the trouble is that when you do the opposite and you just cut fat keeping carbs and protein at baseline the model was correct and I was surprised that the model was correct that the body doesn't decrease the amount of fat that it was burning it keeps burning the same amount of fat and insulin secretion doesn't go down because carbs didn't go down so in this case you also lose fat right the fat that's coming in and the diet goes down you still burn the same amount. You've got to make up the difference from somewhere. It's coming from

body fat. It's always, body fat is always releasing fatty acids and re-synthesizing them. And so you didn't need to stimulate that process necessarily to lose body fat. And in fact, they lost a little bit more body fat. So, but again, tiny, tiny amounts, physiologically, clinically meaningless differences, but from a kind of a theoretical perspective, it suggested that, you know, if low-carb diets are working for some people. It's not because of some magic about, you know, reducing insulin levels and being able to have this metabolic advantage that Atkins had promised in his first edition of his book. He talks about the high calorie way to stay thin forever, right? You just have to lower carbs. You'll burn so much fat and your total calorie expenditure will go up like crazy and therefore

you will be able to even eat more calories as long as you don't eat carbs. You'll lose fat. And what we were seeing was not that. We were seeing something quite different that the reduced fat diet seemed to have a greater effect, although, like I said, meaningless from a practical perspective. And you were pointing out that this was going on for one month with two-week intervals? Yeah, so we brought people in on two one-month periods, five days. They kind of ate this baseline diet to kind of keep them in balance. And then we did another five days or six days where we cut the, you know,

either carbs by 30% of total calories or fat by 30% of total calories. Then they had like three days to eat whatever they wanted from vending machines. Then there was a washout period. They went home and then most of them came back for the second period of time. They got the alternate diet.

Got it. So it's a crossover study. So the same people on the same diets. And yeah, so it's a powerful study design because everyone is acting as their own control. And, yeah, we saw many of the physiological effects that were predicted. And, yeah, it just turned out that that particular mechanism of action wasn't occurring. Despite what was being at that time, we're talking, you know, in the late 2000s, early 2010s,

as being, you know, perhaps the most popular diet that was around. Were there critics at the time saying things like the study was too short? you would see different metabolic adaptations after the fact and what's your response to that's absolutely right yeah and not only was it too short but it's also completely unrealistic right so and and again i'm not trying to give diet advice to people and that was the other thing that was interesting there there were folks on the other side these low fat um especially the there's like this group of uh vegan low fat folks that were out there john mcdougal being one of the most prominent ones who would call me up and invite me to his like, give talks at his, his, uh, his events and saying,

you know, this is great. You know, I'm so sick of the low carb folks. And, you know, you're, you're showing that that low fat is better. I'm like, no, I'm not. I mean, there's like a meaningless difference here. But he was, he saw in our data what he wanted to see and the low carb folks saw in our data what they didn't want to see and made very valid criticisms, um, saying, you know, this is meaningless for most people because you didn't control. how hungry they were, they had to eat all the food and nothing else. You didn't go low carb enough, which is probably true for the way that most people do low carb diets, or at least they say they do low carb diets, was too short. If you'd waited longer period of time, you

would have seen something different. Lots of very, like every study has things that you can point to because you can't control everything. And if you do control everything, then it's not realistic. So it's always this sort of thing. But every study can then build on the knowledge that we have based on other things to try to piece together or triangulate what must be closer to truth than any one single study. So you've taken this first step to try and parse out at least this incredibly controlled physiology of what happens when you cut carbs versus when you cut fats. You've kind of created at least a starting point of it doesn't matter in the short term

in this highly controlled environment. What's the next step? How do you build off of it? Yeah. So we ended up doing, because of these very concerns about you didn't do it for long enough, you didn't go low carb enough. I think one of the other studies that we did next, and this was a multi-site study that I did with colleagues around the country, is we brought in people, 17 people, 17 men actually who were overweight. And we kept them for two continuous months. And we ran them in on this kind of standard American diet that was high in sugar, high in carbs. And we cut their carbs to 5% of their overall calories. ultra low carb. Yeah, so ketogenic diet is 80% fat, kept protein intake constant the whole way along. And there we were really, the main outcome was, okay, if you went to this very low carb diet, could we see this metabolic advantage, the increase in calorie burn that

is seen, or that Atkins has promoted since, you know, the early 1970s, the so-called metabolic advantage. And so what we did was we had these folks for the first month on this kind of run-in diet. were losing weight, which ended up being a little bit of a critique. We weren't able to kind of keep them in weight maintenance. And we sort of had early discussions of should we increase the number of calories? And then do we have to extend the duration of the run-in diet? So we decided, let's just keep calories constant. And we can see if the rate of weight change is altered. The rate of body fat change is altered. And we'll try to adjust for this in the data. So again,

not a perfect study. And then after that first month, we said, okay, we're going to put these folks in these respiratory chambers for two continuous days and measure the total number of calories they burn. And then after a month of this ketogenic diet, we'll do the same thing. Put them in the respiratory chamber for two continuous days. And if we powered the study to detect a difference of 150 calories a day, because our model suggested that there would be some differences in efficiency amounting to a little bit less than that.

And so we wanted to see if there was any additional benefit more than one. was expected. And lo and behold, we didn't see it. In fat loss specifically? No, this was in energy expenditure, calorie expenditure. So they were burning more or less the same number of calories, regardless of this huge swap. And you were calculating for those who lost weight to decrease? Yeah. So if we adjusted for that, yeah, it still was a very, very tiny amount, much less than 150 calories per day. But then what I didn't mention is we actually had people in those respiratory chambers every week for two days. And when we looked early on, we actually

saw a bigger effect. It kind of went up to, I think about 100 calories a day difference during sleep. And then it kind of petered out by the end of the experiment so that when we looked on those final days, that effect had dissipated. But something happened early on, which we still don't really fully understand. I have some hypotheses about what that might be, but those are just that. And so it seemed like the early phase you would see something, not the later phase. So the criticism about not waiting long enough didn't seem to hold up as it went away. As it went away over time. But then, of course, you could say that, oh, maybe it'll go back up again if you did instead

of a two-month study, a three-month or a six-month. Of course, that might happen. But I don't know that there's any reason to suspect that it might happen. The other thing that was interesting was that when we used another method to measure calorie expenditure, something called the doubly labeled water method. At the time, it actually did seem to detect a signal. And it was about 150 calories a day. But that's not how we powered the study. And that method has a lot more noise with it. And we didn't understand it at the time. So we actually published that data. We said, you know, that wasn't the primary outcome. But, you know,

it looks kind of interesting. And it was actually only later that we realized that the calculations for the doubly labeled water method, we actually, they overest, they overest, to make calorie expenditure when you make the wrong assumptions about low-carb diets. And so when we were able to correct those assumptions in a later paper, we actually brought them in line with the respiratory chamber. And that sort of started to make sense to us. Why was there a shift from focusing on fat loss to energy expenditure? Because we could measure it easier in this particular study. And it was also something that people were talking a lot more about at that time was they,

They said that, you know, the calorie expenditure that we could measure in a respiratory chamber has a much tighter confidence interval. It's much more precise measurement than body fat. Okay. And so, and that was another mechanism by which people had proposed. The body fat would occur. Yeah, exactly. It would, if you increased energy expenditure enough by a later time point, then,

then, of course, you could maybe extrapolate to how much body fat loss would be meaningful over a longer period of time. And what I didn't mention is that in that study, I mentioned that people were losing weight and losing a little bit of body fat during the standard high sugar standard American diet. When we switched them to the ketogenic diet in that kind of first couple weeks, they actually slowed down the rate of body fat loss just slightly and then it picked back up again. So that over the both two week periods, sorry, one month periods on each of those diets, they were actually losing more body fat on the higher carb, higher sugar diet than they were on the ketogenic diet. Now, again, meaningless small differences, and the uncertainty around those numbers is quite large. But, you know, it just kind of shows, again, that the body isn't completely perfect.

You don't have to completely be a calorie is a calorie. It just has to be good enough. And that's kind of how evolution works, right? If you, and there's a really good reason why this happens, right? It's because, you know. As humans, you never know what you're going to get. Exactly. And, you know, humans have been successful all over the planet on wide range of different diets.

If you couldn't store fat after a big game hunt, it was like a carnivore-type diet, that would be a big problem, right? So, of course, you have mechanisms to store body fat when you're in calorie excess. And it's more or less equivalent when you account for those incoming calories to a higher carb diet. But there are slight differences that you can pick up in these kind of contrived studies. and that's kind of what we were interested in in delving into i'm curious looking back at it now do you feel like this could be just an assumption of my end that the critics were guiding your research in a way that perhaps you wouldn't have guided otherwise um yeah but i think that's a good thing right i mean i think that there's that you have to listen to critics um when they're making

sensible um do you feel like it was sensible in that case yeah yeah i mean i think like they Many of them went a little over the top with some comments here and there, which I didn't necessarily appreciate. And some of the comments I didn't think were reasonable. But yeah, I mean, I think as a scientist, you have to take, you can't pretend that you've designed the perfect study. And even that study, like I said, there's legitimate criticisms that they were losing weight the entire time. What would have happened if they'd been in a state of weight gain? the folks who talk about the carbohydrate insulin model of obesity will say, you know, we're interested in what causes body fat gain, not what most influences body fat loss, right?

Because those don't have to be the same thing. Right. You know, just because you're able to treat something with a drug doesn't mean that they had that disease because of a deficiency of the drug, right? The treatment doesn't have to be the same as the cause. Right. And so I think that's also a legitimate criticism, right? If you're going to talk about causes of obesity, does this really have a, have a something to say about it?

I think it does have something to say, but I think it's a legitimate criticism that, yeah, we haven't measured people in overfeeding experiments. Other people have and suggest that it actually doesn't, there's not much support for that theory, but we didn't do those studies. Right. Summer's here, and you can now get almost anything you need for your sunny days delivered with Uber Eats. What do we mean by almost? Well, you can't get a well-groom lawn delivered, but you can get a chicken parmesan delivered. A cabana? That's a no.

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sprinkled with pumpkin spice. It's full of real flavors you'll keep coming back for. Made just for you at Starbucks. Do you see any other changes in this research in people's biomarkers? Were you looking at any other variables as not the primary outcome? Oh, yeah. I mean, because we have this wealth of information from these people, right? We measure so many things on them, right?

And I think that's another thing that's important, right, is that people go on these diets not just to lose weight and lose body fat, but for all sorts of reasons. I mean, that's probably a main reason that many of them go on these kinds of diets. Some people find it really beneficial and some people don't. And again, depending on who you're talking to and what sort of tribe they're in, they'll tend to generalize to the other tribe as being misguided in some way. But yeah, so there's all sorts of things that happen, right? I mean, one of the things that was really interesting in that study

when we got to these very, very low carbohydrate levels is that insulin secretion goes down by like 50%, meaning that people don't require as much insulin. to kind of manage their glucose levels on a ketogenic diet as they did on the kind of higher carb, higher sugar diet, which isn't that surprising. And again, it's extrapolation, but, and there's been other studies that have looked at people with type 2 diabetes, they don't need exogenous insulin anymore when they go on and stick to some of these very low carb ketogenic ties, or at least a large chunk of folks. So there are therapeutic uses for these kinds of diets, not to make it.

mentioned the fact that under really controlled conditions, you know, ketogenic diets can help treat children with epilepsy that have been, you know, resistant to pharmaceutical interventions. We did another study where we did another ketogenic diet, which had a lot of, a lot of non-starchy vegetables with it to try to make it as healthy as possible as compared to a vegan diet that didn't have any animal products and was higher in carbs and starches. And we collaborated with folks looking at immune system function and seeing how it seems like, and again, this is early days, and we don't really know what this means, but it seems like when people go on a ketogenic diet, their adaptive immune system is amped up. Whereas when people go on a vegan

high starch diet, their innate immune system is amped up. And both were better than when they started at baseline by various different markers. What that means, I don't think we know, but it's really interesting to see how there's so many different physiological functions that are dependent on the kind of diet that people are on. And what does that mean for general health? We don't know yet. We need to do more studies. What does it mean for people with different kinds of pathophysiologies? We don't know that yet either. There's so much more to learn, which is exciting. Yeah. I'm probably going to be asking you to theorize a bit here, and this is just my medical curiosity, the connection that exists between the ketogenic diet and potentially

helping children with seizures, given your research in the EP world, is there some sort of link with arrhythmias and ketogenic diet that you see a potential for? I don't know anything about that. Okay, got it. Yeah, that's why I don't know. Because what is the mechanism by which maybe, again, you're not familiar with, but for why the ketogenic diet works in those children. Yeah, I mean, there's all sorts of theories.

And they range everything from the, you know, the hottest buzzwords in science of altering the gut microbiome. And that's somehow through the vagus nerve going to, you know, influence the brain and the sort of excitatory potential of. So there's all sorts of theories about that. There's theories about, well, when the brain is running on ketones as opposed to glucose or at least an increased proportion of ketones, that changes the redox state of the cell, and that can change

how excitable it is. And if it's more excitable, then you're more likely to kick off a seizure. All perfectly reasonable sounding mechanisms, but that's one of the things that's interesting in this space is that many folks will have a very convincing mechanism that sounds very sciencey and maybe even quite plausible. And yet, then you should go and try to design a study to test it. whether it's in animals or organoids or humans. For sure. And we're going to go into why that's problematic these days. All right, for sure.

So after you did the next building block of this research of doing the very low-carb diet, where did you go on from there? Yeah. So up until that point, you know, and we did this crazy biggest loser study too, which is another story. Yeah, yeah. Actually, let's talk about that because this gets referenced so much in probably ways that you wish it was going to use. Yeah, that's true. But, yeah.

Well, I mean, up until that point, I've been focusing. on, look, when we control people's diets, right? And we are focusing on how the body is using those fuels and how is metabolism slowing up or speeding down, slowing down, slowing down or speeding up, you know, what are the effect sizes that we're seeing? And there was one case where we actually started to see really big effects, right? And that was this biggest loser study, right? Which was, and again, this was a study that I just was watching reality TV.

and saw these folks stepping on scales at the end of one episode. And I'm like, he lost 15 pounds this way. What the hell is going on? You know, I've been studying, like, we built one of the kind of foundational studies for one of the models that we built was the Minnesota Starvation Experiment, which was done on conscientious objectors in World War II, who volunteered to serve their country by engaging in this starvation experiment. The Ansel Keys conducted.

And they're losing a lot of weight over a relatively short period of, time. And I'd seen people with bariatric surgery losing weight at a pretty rapid pace, but not at 15 pounds a week, right? It was like, what is going on? So I watched more episodes of this show and saw a lot of trainers yelling at people on treadmills and people throwing up and didn't really see them eating much. And so, but the message was clear. It's like the exercise was responsible for the weight loss. But it wasn't clear what was going on in terms of their metabolism. Because there was this idea at the time that if you just did enough exercise, we know from

that Minnesota starvation experiment that people, when they lose weight, by starvation, cutting calories, their resting energy expenditure. The number of calories are bodies burning just to kind of stay alive at rest before you're moving around crashes. And it's viewed as a very bad thing when it comes to weight loss. Of course, for these folks, it probably prevented them from dying in the starvation experiment. But when you say crashes, what is the number drop in the Yeah, so in the Minnesota starvation subjects, it went down by an absolute amount of 40%.

I guess that's a relative amount, 40% reduction. Now, some of that's to be expected just because if we have less cells or less amount of mass of the body, you need less energy to move around. But even when you account for that, there's a greater than expected reduction. of energy expenditure. Was that ever quantified with calories? Yeah. So I'm trying to think of for the Minnesota starvation experiment, I think it was roughly 200 calories a day,

greater than you would expect. So it went down by more than that in an absolute sense, but because they'd lost so much fat-free mass, there was a large expected reduction of calorie expenditure, but even then at the end of the starvation period, it was down by, I think it was a roughly 200 calories. Okay. And so the, and these folks had become very sedentary. It's like they couldn't move like former athletes were like frustrated with themselves. They were failing like their exercise treadmill tests and they just had no energy. They spent most of the time. Fortunately, that was summer in Minnesota. They spent laying out in the sun because they were cold most of the time. And so they just became as you might expect starving people to be ordinary folks who didn't want to talk about doing any of their chores. and things like that.

And so here were like these folks on this reality TV program, losing weight at a much faster clip, doing all this exercise. And I don't know how much they're eating at all. And there was this idea at the time that if you just did enough exercise, you could prevent the slowing of metabolism

because you preserve your muscle mass. And it was clear these folks weren't just doing aerobic exercise. They were doing resistance training, cross-training, all sorts of things. And then there was the other question, well, how much are they eating? And what fraction of the weight loss that we're seeing is because of what's being portrayed in television, which is all this grueling workout and these challenges versus are they eating anything, right? I had no idea.

And so I don't remember how I got this information, but I found the telephone number for the doctor who is in charge of the care of the, he has this nice little Beverly Hills clinic. And I got him on the phone and I actually, you know, for the first time in my life, I pulled out, hi, this is Dr. Hall from the National Institutes of Health. I like to talk to you about the biggest loser program. I was like, oh, yeah, yeah. And he's a very gregarious guy, a really interesting character. His name's Dr. Huizenga, Dr. H. on TV. And he told me about how it was partly his idea for this program because he used to be

the team physician for at that time the L.A. Raiders. And he noticed that many of the linemen couldn't keep their weight up when they did two-a-day trainings. And that was a big problem because they had to stay massive to play the game correctly. And he had the idea of, well, what if we could get people with obesity to exercise as much as a professional football player doing two-a-days? I mean, they wouldn't have any choice but to lose weight. And so I guess that was like part of the pitch for the biggest loser and it became the crazy. I mean, it's nowadays people don't realize how popular. that crazy program was. It was on for many, many, many seasons. But anyway, so I was more

interested in, is it true that they can prevent the slowing of metabolism? Right. How much is the exercise? Because it was obvious to you that they would lose weight with the massive amount of exercise, the fact that they're cutting huge amounts of calories. You assumed right at the time. And yet, and then there was this, and what was being talked about was that they wouldn't have the slowing of metabolism because they were doing this exercise. Right. Yeah. And so, which logically, did that make sense? to you? Not really. That's what I'm saying. Yeah, not really because, and I would always be my pushback against the folks who made that claim, because when you look at the resting metabolism

of skeletal muscle, it's really low. It's only 15 calories per kilogram. A kilogram of muscle, like 2.2 pounds of muscle. It's hard to grow 2.2 pounds of skeletal muscle, all for the benefit of a deficit. Yeah, while in a deficit, right? And all for the whopping benefit of 15 calories a day. Are you kidding me? This is like nonsense, right? But, you know, maybe there was something else going on with exercise. Maybe there was some sort of hormonal thing or inefficiency and the rebuilding of the proteins cost energy. There's all sorts of reasons why that might increase metabolism. So it wasn't a no-brainer that this could be complete fallacy.

So you are open to it. Yeah, of course. That's how I think everybody should go into every sort of study. They're contemplating. And so I got them on the phone. I'm like, okay, well, do we know any? about how many calories are burning? He's like, well, they exercise for like three hours a day. Jesus. And, you know, we can make some guesses, but no, we don't have any direct measurements.

I'm like, do you measure how many calories are burning at rest? He's like, yeah, no, we don't have anything on it. Okay. Do you know how much of the weight that they're losing comes from like body fat versus muscle? And he said, actually, yeah, because this is Beverly Hills Clinic was decked out with all the same body composition assessment equipment we had at the end. They had a Dexas scanner for very large people. They had a bod pod. They had bioimpedance. They had all sorts of toys.

And so he had data from all the seasons of all the contestants. Yeah, that's his wheelhouse. That's what he's interested in. Yeah, they lose by far more fat than people who are on bariatric surgery. And that kind of makes sense given the exercise that they were doing. And like, how much are they eating? It's like, oh, well, we give them instructions to eat above a certain amount. like okay um how much are they eating it's like well we don't know like oh they don't prepare

they they they don't get their meals prepared for them it's like no no no they they do it themselves and they just have a kitchen at this ranch in malibu and it's stocked with like the promoters of the show like i think at that time was genio turkey oh it's like everything jenio turkey in this in this refrigerator anyway so i was like well you know i'd be really interested in having like one of my postdocs come out and maybe make some measurements on some of the contestants over the course of one of the competitions. And he was really into it. And he was like, yeah, let me talk to the producers. And eventually that's what we ended up doing. I worked with a colleague of mine, Eric Ravison at the Pennington Biomedical Research Center. Another long story.

The NIH wouldn't let me do the study. They said, no, we're not going to associate ourselves with reality TV. one of the missed opportunity there yeah and and I sort of thought I'm not one to take no for an answer at least not the first answer and so I met Eric at a conference and I said Eric have you ever seen this show he's like yeah it's a horrible show I was like when I was president of the obesity society we wrote a scathing letter to NBC about how stigmatizing it is I'm like yeah yeah I agree wouldn't you like to study them he's like I got his postdoc interested and eventually we took the protocol I'd written for NIH and modified it for their IRB and it got approved there.

And so we sent out our postdocs and some equipment to Malibu to test. In fact, we sent supplies to the contestants before they knew there were contestants. At home, we got like the list of the folks who were selected and we gave them scales. We gave them doubly labeled water and to measure how many total calories they were burning even before they knew they were on the show. And then when they went to Malibu, we set up like a little pseudo metabolic unit where we had people measuring their resting metabolic rate with metabolic carts. And we designed the study to just assess, did their metabolic rate change by the amount that you'd expect given their weight loss? Or was there something extra going on?

Or were they able to preserve their metabolic rate at a higher level as many of the folks in the exercise and physiology community had predicted? And so, so yeah, so we went back out there several times. I say we, mostly the postdocs, again, don't let me touch equipment. And when we got the numbers back at the end of the weight loss program, it was really interesting because they had on average, they cut by about 65% of their calories, huge cut in calories. Right away. Yeah, like during the competition, they just cut calories. enormously and they were doing the equivalent of three hours of vigorous

exercise a day and their calorie expenditure went up by about a thousand calories per day and so they're eating this huge deficit and they're losing weight at a rate of a pound a pound a day of that's the other thing TV time is not real time right so 15 pounds 15 pounds a week it's more like 15 pounds over 12 to 15 days right that's between episodes right right So it's not a real week. So that was one thing I learned really early on. But so, so, but on the average weight loss was a pound a day when they were on the ranch.

When they went, there was the way the show worked is that people got voted off. Occasionally then at the end of 13 weeks, everybody went home. They came back at week 30 for like this, this reunion or, I guess the finale of the TV show to whoever be crowned the biggest loser. And at that point, even when they went home, they're still losing weight at about a pound. half pound a week, a day, sorry, half pound a day. So cutting their rate of weight loss and half, but still a huge deficit and still doing about an hour of vigorous exercise every day of the week. So the idea that people with obesity don't have willpower is just nonsense, right? This is like an insane amount of willpower. And then they left their families while they were in

Malibu, but they came back and they tried to go back to their usual life. And yet they're still able to do this for, you know, weeks and weeks and weeks at a time. And then when we looked at the metabolic rate, it had crashed. It had clearly gone down more than you would expect based on their body composition changes. And we're talking on average 400 calories a day more than you would expect. And the way that, and then what we were interested in was did that slowing of metabolism predict who would regain weight later? Because that was another kind of myth that was out there. It wasn't a myth at the time we didn't know, was that the people who would have burnt the fewest number of calories because their metabolism had slowed down the

most, they should be the ones who are most susceptible to weight regain. And so we brought, by this point, the NIH should kind of come on board. And so at six, the six year mark, we brought everybody back, actually minus two people, to the NIH clinical center to have the kind of follow-up measurements. And on average, they regained about two-thirds of the lost weight, We had one person continue to lose even more weight. Some people regain all of the weight and more. So it was a wide range of weight regain and continued weight loss. But there was no relationship between how many calories their metabolism had slowed at the end of the weight loss period.

And who had regained? We couldn't predict it. And the most shocking thing and the thing that got all the press attention was the fact that despite regaining the weight, like we mentioned before, larger bodies have higher metabolisms, burning more calories at rest, they're on average didn't change from at the end of the weight loss competition. So they permanently decreased? It was decreased. Yeah.

It was still at this low level. Even though they were a third still lighter? Because they regained two thirds, but they had a third lighter than when they... Yeah. Yeah. So they were still down by a third on average. And my expectation was that their resting metabolic rate would go on. up as they regained weight and they didn't that didn't happen and that was like so shocking to me

i was like all right what's different between when we measured it then and when we measured it now we realized we were using different actual pieces of equipment to measure metabolism we used the one from the pennington center when we were out in malibu using the nihish one like okay well we calibrate them on both occasions but it's possible let's fly the one at the pentington center to the NIH to check and see if they're measuring the same. And that wasn't it. They were measuring the same thing. So we had no choice but to kind of, you've got to believe the data as unbelievable as it is.

And then it got even stranger because when we look to see who was most successful at keeping the weight off, it was the ones who continued to have the greatest slowing metabolism. It's like contradiction after contradiction of what you would expect. And it turned out that that was also true in Malibu. The ones who had lost the most weight were the ones who had slowed their metabolism the most. And another piece that was kind of interesting was that when you looked for a correlation between who was doing the most exercise or the most physical activity versus who was cutting their calories and their diet the most, it was there was no correlation between the differences in physical activity and weight loss, but whoever cut their calories the most lost the most weight. They were the ones who kept their, had the greatest slowing of metabolism and the complete flip at six years. The ones who had, the ones who had increased their physical activity the most, had the slowest metabolisms and had the most success at weight loss.

Whereas energy intake didn't, or calorie intake didn't, there was no correlation there. So really weird stuff. Turns out that, you know, some of those things have been replicated in other cohorts, right? But not all of them. And there's still some mysteries there. But the way we like to think about it, or at least the way I like to think about it now, is the only way to make sense of that relationship between energy expenditure and metabolic slowing and weight change is that it's a response, not a determinant.

In other words, think of it, think of that metabolic slowing like the tension on a spring, and you've got the spring, you're not doing anything, and there's no tension. You pull the spring, that could be the equivalent of weight loss, however much you can pull the spring, you get a greater tension. And there's a greater pull back. And so that's the metabolic adaptation. You pull more, you get more weight loss, and you get more pullback. But it's always in proportion to the, it's a proportionate response to the amount that you're pulling. So for whatever reason, the people who are most successful at making those lifestyle changes, either on the ranch and the biggest loser competition or in their live six years,

later, we'll get the most weight loss, but they'll also experience the greatest tension on the spring, the greatest amount of pullback of metabolism. And the frustrating thing was that when we reported that and it got all this press attention, it was like literally on the front page of the New York Times, no one reported it right. How are they reporting? They were saying, oh, it's the slowing of metabolism that caused them to regain the weight. Which is not the pattern. It's not the pattern. We saw no correlation between those two things. And that this is the reason why they can't keep the weight off. I was like, no, the people who kept the most weight off,

even lost even more weight, they had the greatest slowing metabolism. And so it's not determinative. It's not helpful necessarily. In other words, if it didn't happen. The spring analogy works because you're essentially, the spring ends up losing its elasticity. Yeah.

If you magically, you're pulling at it with the same tension, you magically cut the tension on the spring. Of course, you'd pull it to infinity, right? But so you would be even more. successful, right. But meaning that it doesn't, at some point, it doesn't bounce back. At some point, it doesn't recoil. Well, no, at some point, that would make it easy, right? Then you would suggest that the people who are most successful, if you've waited long enough, we should have the least tension in the spring. That's not the case, right? I don't think it resets that way. At least we didn't see

any evidence of resetting over six years. But how come when they gain the weight back, like what is your theory as to why the rate didn't go back up? Yeah, I mean, there's, that's what I mean yeah yeah yeah so so again complete speculation but when you look at um there's this idea from um ecology where we have energy budgets for different um different amounts of everything that we do in our bodies is cost energy right yeah um and this was most recently popularized by herman pontzer who wrote the book burn which is a great exposition on this idea um because he looked at hunter gatherer tribes who are very physically active and they're also smaller. So you have to adjust somehow by their body size. But when you adjust their body size and you look at how many calories they're

burning in total, it's no different than sedentary office workers. And so for a wide range of physical activities, it seems like there's some sort of trade-off going on. And so what we saw in the biggest losers was that the ones who'd become the most physically active. And by the way, they'd all become much more physically active than they were at baseline. Right. That perhaps, for many, many good reasons, their metabolic rate dropped. So for example, if, you know, their liver is making less pro-inflammatory proteins, right? Protein synthesis is an energy-consuming process.

Maybe that is getting toned down because they're now more physically active. We know physical activity does have a beneficial effect on these kinds of processes. Other cases are, you know, the example of, you know, female athletes who do or training for marathons and things. They stop menstruating, right? And so there's an energy cost to doing that. Maybe this kind of budgeting of energy is changing depending on the amount of physical activity. So I think that on average our sort of guess, and it's only a guess, is that people when they started the biggest loser competition, they were not particularly active. they become crazy active during the competition unsustainably so but many of them kind of are able

to incorporate that into their daily life and even though they regained two-thirds of the lost weight by the way they're still down i think 12% on average from where they started six years before and the ones who are most successful are doing the most physical activity and they're the ones who have the greatest slowing in metabolism so maybe there's this interplay between the energy that your body's devoting to physical activity and these other compensatory metabolic changes that are going on. Complete speculation. Speculation, but it would strengthen the notion of why it's so difficult to lose weight

with just exercise. Yeah, yeah, absolutely. I mean, there is that aspect. And that's been one of the messages that Herman Ponsor has been talking about. And there was a recent paper about this in a big cohort of folks using doubly labeled water and resting energy expenditure. But it really spoke to the idea that you could have these big effects on metabolism, finally, but they worked in exactly the opposite way that many people thought they would work

in terms of how they relate to weight loss and success at maintaining weight loss. So you do this research, you find all of these very interesting, perhaps unexpected findings. The New York Times is publishing the incorrect evaluation. They got some of it, right? Well, right. They got some of it right. But the major takeaway, they kind of flipped and went in the wrong direction. What do you do?

It wasn't just them. I mean, even my co-author of the book, she admits, oh, yeah, I've reported that wrong, too. So what, what do you do in that moment when you're seeing these headlines pop up? And you're like, well, wait, wait, that's not the. Yeah, I mean, well, the thing is, is that the other thing that was obvious was that people were clearly tying the concept of metabolism to weight in a way that wasn't accurate and was also. very distracting from the really wonderful science of metabolism, right? That metabolism is in common among every living organism. And even folks when they look for signs of life on Mars, they look for signs of metabolism. And it's because it's so fundamental, it's the thing that

allows, you know, complex organisms to be there because that process by which we're harnessing the, you know, energy and matter from the foods that were being provided, or even the sun and the air in the case of plant metabolism. And this flow of matter and energy is what allows humans and every other living thing to exist. And so it was frustrating to kind of see the popular concept of metabolists, not only being wrong in terms of its directionality

of its predictions, but it's link with weight as the only thing that's important here. And just ignoring the fact that every cell of our body is doing metabolism. It's this complex like biochemical waltz of miraculous ability to kind of turn the food and air that we breathe into, you know, everything that we are and everything that we do, as my friend Charlie Brenner likes to say. And just missing that, the wonder and awe of that process, which I think is just fascinating. And that's kind of part of what our book is about is to kind of give people that appreciation and the idea that, you know, we're thinking of this

this miracle of nature as, oh, it's just about weight, right? I'm curious to better understand your speculation as to the exercise being the component that's driving the potential drop in metabolic rate. What if, let's say, the biggest loser had no exercise component. Yeah. If it was just strictly a mini starvation experiment, essentially, would you have expected to see the same in the speculation? Yeah, I mean, there have been studies that have looked at people who have lost weight and

regain some of that weight, and they did not have an exercise component, and metabolic rate goes up. Interesting. And not only that. So then it's not speculation, then. Well, is it backed by some data now? Well, it's a different group of people, and there are limitations to those studies as well. You would have to kind of, the way you would do it is you'd do a randomization, right?

You'd take a group of people and you randomize them to a diet alone or a diet plus exercise, and you'd follow them up for long periods of time and you would measure different components of energy expenditure, their body composition over time. And that was the other thing that was really interesting was that as silly and stupid as this biggest loser study was,

there are a very small number of studies that have made those types of repeated measurements on the same people over time as they undergo major changes over years. You've got your, you know, several week long weight loss studies, maybe a year long weight loss study, and then you kind of let them go and, you know, maybe we'll see what happens in some subset of them. But that's not often the case. And those are the rare, those are the very rare examples. And who knows, maybe that's because of the

funding cycles and the only last typically five years or so. It's not exactly clear why that's the case. But yeah, I was shocked when I went back and said, okay, well, how many studies do we have to compare this to, even the silly non-randomized study, kind of an opportunistic experiment that was natural experiment, natural experiment that was happening, there really aren't that many, but the ones that we do have didn't involve a lot of exercise and they did see their metabolic rate going up, which again, lends some support to that speculation, but I think it really is speculation. You could do that study better, obviously. How were people these days misusing the research from that study?

or misapplying the research. Yeah, I mean, I think it's still the same thing, right? Which is that they think that metabolism is somehow determinative of weight loss success. And it wasn't in the biggest loser case. And it kind of actually speaks to what ended up being a huge shift in my research program, which was I've been focusing on either really small effects of like carbs versus fat and energy expenditure or body fat changes or even in this case, a big effect on metabolism that turned out to work in the opposite direction.

So I started to think, okay, well, maybe more of the action is happening on the appetite and food intake side of the equation, right? We'd been doing these studies where we were measuring what people were eating or even controlling what they were eating, but we hadn't done studies where we tried to let people eat whatever they wanted and try to understand how is appetite controlled. How does it relate to body weight change? Is there some sort of feedback of as people lose weight, do they become, does their appetite go? Yeah, I mean, there's anecdotes about this and people report this and have even seen changes

in hormone levels that would tend to support this, these appetite-related hormones. But how is that quantitatively related? How does that play out over long periods of time? And what is it about our foods and our food environment that might actually change the basic biology of appetite control. And that gets now to the question of why do we have, you know, an epidemic of obesity? What's different now compared to before? We know that, you know, a huge chunk of the heritability of obesity.

There's, you know, somewhere between 40 and 60 or 70 percent of body size in a given environment is heritable. And we've now come up with more than a thousand different genes or at least single nucleotide polymorphisms that are correlated with body size, BMI in particular. Most of those, the vast majority, seem to be genes that are acting in the central nervous system, in the brain likely. How does that work? You know, what is going on there? And what is the interaction between those genetic susceptibility? and our environment. Is it on the physical activity side of things? Is it on the food

environment side of things? Is it something completely different in our, in our environments that may be causing this change? Or is it, you know, a general lack of willpower that manifest simultaneously. Which some people believe is. Yeah, simultaneously in all people around the 19, you know, mid-1970s and 80s, right? By the way, there have been folks who've studied this, right? They've looked to see, well, are there other in other kind of metrics that might be about conscientiousness and willpower that, uh, you know, did, did people, um, you know, wear seatbelts and like these kinds of behaviors that, and there's no difference in the rates. Obviously, when before seatbelts were popular,

it's not a good example. I don't remember exactly what the examples were, but there was no evidence that there was these dramatic changes in conscientiousness or, or willpower over the course of the time that we had this increase in obesity prevalence. Um, and the fact that it happened simultaneously in all age groups and all internationally. But it's not simultaneous internationally, right? Because it took a while. We were leading the world in that respect in some sense. So what is it?

And can we actually even explain that based on just the changes in the food supply? That would be one thing. Or can we explain it based on changes in physical activity? So I got interested in those kinds of questions. And then so I was trying to, you know, building these mathematical models of how, you know, how much does it cost to gain weight, how many calories does it cost to gain weight and deposit tissue and how does metabolism change? How does body composition change? And how does energy expenditure change? And that would have been like much of my research previously. And I was working with my colleague at NIH Carson Chow and he just asked a really simple question. It's like, did the calories go up enough in the food supply to explain obesity? When I found out my friend got a great deal on a wool coat from winners, I started wondering. Is every fabulous item I see from winners? Like that woman over there with the designer jeans.

Are those from winners? Ooh, are those beautiful gold earrings? Did she pay full price? Or that leather tote? Or that cashmere sweater? Or those knee-high boots? That dress, that jacket, those shoes. Is anyone paying full price for anything?

Stop wondering. Start winning. Winners. Find fabulous. for less. It's a really good question, right? We have data about what's in the food supply. We don't have data about what was eaten, but we have data about what was in the food supply, and we know what it was in the U.S. for very long periods of time. Because currently it's around 4,000 per person. Yeah, it's around 4,000 calories per day per person in the U.S. is available to be

eaten. And, you know, in the 1970s, it wasn't that. It was about 3,200. or so per person per day. By the way, and clearly we're not, we're not eating that number of calories. Of course, yeah. Well, at least you can't point to something to prove that. Well, that was kind of, again, what we were trying to figure out because, you know, we know something now. We've measured a lot of people about how many calories they're burning just to kind

of maintain their weight. We know a lot about the calorie costs of weight gain. And so that was a question that we asked. Was that increase in the number of calories in the food supply since the 1970s enough to explain the average weight gain of an American. And it turned out it was way more than enough. So of that, you know, 800 to 1,000 calorie a day increase in the food supply, only about a third is accounted for by the gain in body weight of the population.

Two thirds were missing. And we're like, what the hell's going on? We called it the dark matter of all these at the time. And then it occurred to me that, um, there's actually some data that we could look at because the EPA collects data on what's in municipal landfills, like how much construction materials there and how much food waste, solid food waste, is in municipal landfills. And they've been tracking this for decades. They don't normalize it usually per person in the population. So we took the census data and we normalized it. And we could

track the same 50% increase in food waste since the 1970s. which was calculated based on our model that two-thirds of the extra food calories in the food supply that wasn't eaten represented about a 50% increase in food waste. And the EPA numbers turned out to be exactly the same per capita, 50% increase in food waste found in municipal landfills. So we were basically this calorie glut in the U.S. food supply that at least could more than fully account for the obesity epidemic and in fact

accurately predicted how much food was wasted which was really interesting and so yeah it really raises the question okay well what is it about our food environment that's how are some people resistant to this? Clearly we didn't

eat all of those extra calories in fact two thirds of those extra calories went in the trash what's the biology by which changes in the food environment change how much we eat I mean it could have been 100%. It turned out to be, you know, not 100%. It was, you know, only a third of the increased calories that were available were eaten. How are we so successful at getting people to eat those extra calories or how it's the food industry and the food environment so successful? And what was it

about those food environments that has driven this increase in calorie intake? And so we decided to do some kind of silly, again, silly studies saying, okay, well, we can take people and put them in a very artificial environment and control their food environment. And just give them more than enough food that they would need to eat in order to maintain their body weight. In the first study that we did of this kind, we kept the macronutrients the same, so carbs, fat, and protein more or less the same, amount of fiber was the same. The glycemic load of the diet was the same. The sodium content was the same. And in one case, we basically said we're going to design a diet that was 80% of these so-called ultra-processed foods, which we could talk a little bit about. I know you've had

others on your podcast talking about this. And in another case, we'll have no ultra-processed foods, all just like 80% of calories from minimally processed foods. And just give people really simple instructions. We're going to meals will all be prepared for you. You don't have to do any work. You don't have to buy the food. We're just going to give you three meals a day and snacks. Eat as much as little as you want. We're not even going to tell you why you're in the study. We're measuring lots of stuff. We're interested in how these different foods affect your health. And you're blinded to your weights, you're wearing loose-fitting scrubs so you can't tell if your clothes are getting tighter or looser, and just eat as much or as little as you'd like. And in that study, I kind of thought that if we match for the nutrients and give them the same number of calories and they don't have to do anything, they'll probably eat more or less the same amount.

and maybe this idea of ultra-processed foods has more to do with the economics of food and how they're advertised and whatnot probably not something about the foods themselves but I'm happy to be wrong and if I'm wrong then we'll show something else maybe maybe they eat more of the mentally processed foods who knows what's going to happen right and it was the first kind of study that I'd done of this kind of focusing on the food environment and people choosing whatever they wanted to eat the more behavioral aspect Yeah, exactly. And I was really surprised to find that these same folks, again, random order, two weeks on each of these different diets, same people, when they were exposed to this ultra-processed food environment, for whatever reason, they chose to eat more calories, about 500 calories per day more than when they were on the minimally processed diet.

And they gained body weight, they gained body fat. And when the same folks were on the minimally processed diet, they lost body weight and lost body fat. And when we looked at their blood markers, in fact, the biggest difference from baseline was the minimally processed diet because most of the U.S. food environment is already ultra-processed. It's a hypothesis about why we saw that. But, you know, for example, like, and again, these are not primary outcomes. The primary outcome was the difference in calorie intake. But when we were exploring these other things, you know, C-reactor protein, which was, you know, not high, but it was somewhat elevated in folks at baseline, you know, two or so. it dropped by 40% on the minimally processed diet after two weeks and stayed at the same level

of two or so in the case of the ultra-processed diet. So it was really the minimally processed diet that were driving some of the biochemical changes. But then they were gaining weight and gaining fat on the ultra-processed diet. And so that kind of was surprising. And I think again, it's one of those things where you're like, okay, now I've got to try to figure out what the hell's going on. But, yeah, for whatever reason, the diets that we provided to these folks, and that's the other thing, they didn't report them being any more pleasant. So we had them rate the meals. And they're also reporting eating to the same degree of appetite, same amount of hunger, fullness, satisfaction, eating capacity. Yeah, meals are equally pleasant, but for whatever reason, they're eating more calories on the ultra-process diet.

And that study got way more attention than the biggest loser study. You got more attention than any other study I've ever done. And people had some very strong opinions about, you know, what's going on. And again, it's one of those things where everybody sees in that what they want to see, right? The low carb folks are all of a sudden, no, it's highly processed carbohydrates that were driving it, right? And the low fat folks, it's like, oh, it's too much saturated fat. The seed oil folks are like, oh, there's the omega-6 to omega-3 ratio is all off. And so, and folks who've been studying eating rate noted that, yeah, in fact, people ate the ultra-processed meals more quickly than the minimally processed meals.

And, you know, we saw some. And the marketing folks were like, all the foods are more colorful and pretty. Yeah, who knows, right? So all sorts of things. And it was so interesting because they're all perfectly plausible sounding explanations, right? And even from scientists, right, who see in their body of past work, in this study, it's like, oh, well, this, I know how to explain this. And many of them very confidently said, I know what's going on. Oh, great. I guess I don't need to do any more work. I'm done.

Just tell me and you'll write it up. And I think they got frustrated because I would say, well, yeah, that's a great and really plausible thing. But we have to study it. We have to actually design a new study to determine what's going on. And, you know, we did a bunch of, we worked with some of them to kind of do post-talk analyses of let's take the meals and say, well, the meals were, the overall diets were matched for these different macronutrients, but on a meal-by-meal basis, they could vary quite a bit. Some of them had higher protein than others was protein a correlate. So we do some statistical analysis.

And again, that was another funny thing. It's like the higher protein meals led people to eat more calories, which is not what a lot of people would have expected. And I'm against association. We didn't do a trial to test that. It might work out to be the opposite if you actually did a trial. And, you know, other folks were like a colleague Tara Fazzino from University of Kansas, said, yeah, I know you matched the overall macronutons, but what about an individual

foods? Did you present people with more foods that crossed either high fat and high sugar? So the overall diets are matched for fat and sugar. But maybe individual foods, maybe you gave them more individual foods that had these pairs of nutrients that she calls hyperpalable, either high in fat and sugar, high in salt and fat, or high in carbs and salt. And sure enough, when we looked at the data, it's like, yeah, we actually did give them more individual. Well, that's, there is not, there is some non-overlap. Okay. There is, there are some ultra-processed foods that are not high in both of those nutrients.

Okay. And so when we did some analysis, it turned out that, yeah, that actually, actually might explain some of the effect. Another person, Barbara Rolls at Penn State University, has done remarkable career looking at the energy density of diets, so the calories per gram of food. And she said, well, yeah, I know that the energy density of the overall diets was matched,

but if you take out the beverages and you just look at what's on the plate, the ultra-processed diet had much more calories per gram. And she's right, they did. And there's this argument about whether or not beverages can contribute to, you know, appetite control or not and whether or not they can, you can dilute the overall energy density of your diet by, you know, drinking more water or something like that. But she's right. When we took out the beverages, the calorie density was different. And it's interesting, right, because the macronutrients are the same.

So it's not because it has more fat versus carbs. And remember, fat has more calories per gram than carbs. It was because the ultra-process foods are drier. they have less water in them you've destroyed the food matrix the cellular structure of the food and and that's actually on purpose because um you're trying to extract the water to make them more shelf stable and prevent bacterial growth so really good things to do if you're going to have and potentially lead to overeating yeah well yeah who knows right theory yeah in theory right and so and so energy density turned out to also play a role in our post hoc sort of analysis and other folks had other

ideas like the ratio of overall carbs to fat and we've worked with them to kind of look at some of these other things. But at the end of the day, you've actually got to design a study to test it, right? And you can only design its study to test so many things at once. And so before I left NIH, we'd started that study. We'd been running it for almost three years because it takes forever to do these kinds of studies. Because the facilities that we were doing it at where we kind of bring people in, house them for a month at a time. And even for modest-sized studies, we can only house nowadays about two people at a time. So to do a study... Why is that a limitation of cost? It's, well, it's a limitation of the facilities. So it's basically a hospital ward.

Hospital awards are expensive. You have to have nursing care. But for our studies, you don't really need all that degree of expense. And that's something that I've been, had been working with NIH folks for years about could we could we just rent like a retreat facility for a summer and bring in everybody at once and hire some staff to kind of go out there and measure all these things we'd have a study that takes three years done in a matter of three months over a summer and we were working on kind of doing some pilot studies like that and even broader i was like you know if we really and i was trying to get the new administration interested in actually developing a facility like this not just for us but for nutrition scientists all over the country to do the best quality science where we have the

most control over people's environment for not just food environmental exposures, other environmental exposures, and be able to test some of these hypotheses that are now being treated as facts. Right. And so anyway, it takes a really long time in doing this for the three years. And so we designed this study to try to get at what was it about ultra-processed diets that were driving people to over consume calories. And as we speak, the last participant is currently enrolled at the NIH. It's been about three years since we've been doing this darn thing. And hopefully we'll have an answer for that question soon. Interesting. This is going back a bit. It stuck out

in my mind in the Minnesota study where it wasn't exercise driven and it was nutritionally driven weight loss. We saw the rate drop, the metabolic rate drop. After they were fed, was their data collected if their metabolic rate return to normal? Yeah, so they did follow up a subs. So they did, the study was actually designed for the rehabilitation phase. So these folks were conscientious to the projectors, not starving for the sake of starvation, but because people in Europe were starving during the war. And Anselkies wanted to know what's the best protein relationship, what's different amounts of vitamins do we give, what's going to have the best benefit in terms of rehabilitation? The short answer was that, and he had them divided

up into different groups with different kind of re-feeding diets. And to his surprise, there wasn't any measurable differences between the different diets that he designed. So he had this refeating phase. And yes. Which needed to be done carefully to avoid refeating syndrome. Exactly. Absolutely. Yeah. And it was done in this very stepwise methodical manner. Were they aware of that at the time? Or did that develop from his research? No, I think that they knew something about refeating syndrome, just in treating like cases of severe malnutrition in the past. So he was very aware that he had to ramp this up slowly. And so, yeah, so there was this period of ramped up where it's very controlled,

kind of gradually introducing the calories and people were regaining weight. And yes, their metabolic rate started to climb. So again, another data point suggesting that the physical activity might have played a role in the biggest loser folks. And then he had a subset of them after the main study was done. And he said, okay, just eat whatever you want. And they hadn't recovered all of their body weight yet. And they ate like at that point, I think it was like almost 6,000 calories a day for a while. Like they way overshot what they were eating initially.

And that eventually came back down as they regained all their weight and all their body fat. So yeah, so it was a really interesting study, again, suggesting that there might be some feedback between how much weight you've lost and the signals to your brain to kind of recover weight that has been lost. Yeah. And I would argue that that set point is, well, we've got, if there really is a set point, then why is it that when I change someone's food environment, all of a sudden they're eating 500 calories per day more gaining weight? And the other case, they're eating 500 calories a day less and losing weight, right? So it's hijackable.

It's a resettable set point. Actually, we're, you know, some of my colleagues that are doing these really sophisticated neuroscience experiments in mice are starting to piece together how that works. And it's really the early days of this. But the point is that these are not just kind of independent ideas of our food environment really does affect the biology of appetite control in very fundamental ways. It's not just like I used to have this analogy that I used to think about of maybe what's happening is, you know, it's like you're well it's a very hot day in new york here today maybe if it was um you know we have an air conditioning system that works and can keep this room pretty comfortable but if it

goes up another 15 or 30 degrees outside right the air condition's nothing broken right the thermostat still set at this level yeah maybe it's just being overwhelmed now right it's always on but the temperature difference between inside and outside is too much maybe that's what was going on with these different food environments, right? You're being this, the same physiological system as just being overridden. That's the way I used to think about it. I don't think that anymore. I think that you're also just resetting the thermostat. And that's based on, you know, what little I understand and know about the biology of how the so-called hedonic and homeostatic feeding circuits actually interact with each other, how different food environments affect where animal models are regulating

body weight. There's this classic experiment that Tony Sclafani did, where he gave rats a supermarket diet. And he was able to see that for the first time in his experience, he was able to get adult rats to gain weight at a rate that was similar to when he ablated part of their brains. So something about the food environment is actually affecting our brain in ways that we don't fully understand. And it's doing it more like resetting the thermostat than it is overwhelming the air conditioning system. Kind of to maybe make an analogy to a person listening who's not a researcher in this space, the opposite of a GLP1.

Like an anti-GLP-1. Right. And yeah, and how GLP1 drugs work and how bariatric surgery works to reset at a lower level, I think, again, are really amazing questions that we haven't fully worked out. And it's not like people initially thought for Barry. psychiatric surgery. Oh, you're just not absorbing the calories. It's like, no, for most bariatric surgeries, you know, digestibility and absorption of calories is, is pretty darn good, right? There's some malabsorptive procedures, but those are few and far between. And GLP1s are

working to somehow reset our appetite control in a very unphysiological way, right? I mean, the GLP1 is a naturally occurring hormone that goes up after, after eating. And, and now we're able to pharmacologically increase it by, you know, a hundredfold more than the normal levels and keep them high for, you know, a week at a time. And that's not a normal situation, right? That's, that's a very abnormal situation. Again, it treats obesity and type 2 diabetes quite well in many people, but it's, again, it's not because they were GLP1 deficient, right? And that's not the cause of the obesity epidemics. Also, this is a curiosity point of mind, because in all of these studies where we're looking at

the decrease in the metabolic rate, perhaps tied to initial weight loss based on nutrition, perhaps retained drop in metabolic rate from perhaps exercise, that's in individuals who are losing weight, who perhaps had some sort of malnutrition state, right? So what happens in people who are, let's say, high performing athletes or people who exercise regularly, does that mechanism still hold true in them? Or is that a completely different model? Yeah, that is not my field. And I don't know enough about it. I was really interested in this idea of professional athletes after they retire, right? Because again, the idea that they're doing so much training and they might be so focused on their nutrition and building muscle and trying to

be so efficient and different kinds of sports have different, you know, different things that they're optimizing under. And what happens after they retire and are no longer doing that? I think that's a really interesting question. I haven't done no research on that. Because I'm just trying to follow if we do the speculation of exercise impacting metabolic rate. I could think of a retired NFL player, how easy it might be for them to gain weight if they've hurt their or lowered their metabolic rate.

It's a perfectly reasonable hypothesis. I guess the question is, is it true? Yeah, exactly. Or is it more again on the food intake side of the equation? And is metabolism only responding to those changes and those other lifestyle changes? And again, I just want to be clear. Exercise is great. Yeah, we're not saying.

But yeah, it's one of those things that, and in fact, like the biggest loser suggested, it might even be beneficial. And other studies have shown this, too, for weight loss maintenance. again, the people who were the most physically active at six years tended to maintain the most amount of weight loss, they also had the greatest slowing of metabolism. So again, metabolism following the horse, not leading the horse. Yeah, very interesting stuff. Before we get into the current state of research and where you are now, take me through your thoughts on the competing models. Based on what we know now, calorie is a calorie. Calories in,

calories out versus CIM model. Okay. And there's all sorts of other things in between, yeah. The reason I bring up those two specifically is there's been some guests on the channel that I've had debates with me about what they think is going on. They disagree that dropping someone's calories will lead to weight loss, calories consumed, would lead to weight loss. They explain that they believe if you cut someone's calories by even 800, let's say,

that there wouldn't be weight loss long term because. because their body would adapt to that 800 calorie deficit. And my response has always been, like, even in the biggest loser study, we saw 400 calorie drop in extreme weight loss. How would the body compensate 800 calories? So what's your thoughts on that? I mean, so I think that the point that they are trying to accurately make is that that calories in calories out is not like a zero interest bank account, right?

Okay. So if you think of your body fat as being the balance in your bank account and all that happens if you withdraw more than you're putting in is that you linearly will or if you if there's a constant imbalance then you will just withdraw all your money until it goes negative right until you start owing the bank money right and similarly if you eat a little bit more calories than you burn then you'll just accumulate body fat in this case you're depositing a little bit more than you than you're withdrawing you will gain as much money as as you need these two things calorie intake and calorie expenditure are not independent quantities in the body, right? So like we'd mentioned

before, you cut calories in the diet. Yes, calorie expenditure goes down and appetite goes up. We did this really interesting analysis with my colleagues at Johnson and Johnson, where they were giving SGLT2 inhibitors. These are drugs that increase the amount of glucose that spilled in the urine and people with type 2 diabetes to manage their glucose, but it also acts as a sink of calories, right? And And for the higher doses, you're getting to about 360 calories a day lost. And it's pretty consistent after the first initial period. And cardio protective. Yeah, there's all sorts of really interesting questions about how they have those

effects and they're really interesting drugs. But I was interested in the question of, okay, well, in a placebo control trial, do these folks lose as much weight as you'd expect based on the calorie output side of the equation? right now you're increasing calories out by 360 calories per day and they lose weight and they plateau after about a year and on average in this placebo control trial i think they'd lost four kilos so not nothing but if you actually did the math they should have lost three times that amount and what it ended up happening we we validated a model to kind of try to predict how calorie intake changes very slowly over time was that people compensate for a huge amount of those um those

excess spilled calories by increasing their appetite. Oh, okay. Yeah, so they're eating more calories. They're eating, they end up eating very close to the 300 plus calories per day, more after one year. Their overall energy expenditures drop by a very tiny amount because they only lost four kilos. And the thermic effect of food is only 10% of that drop.

It's actually maintained because it's going up a little bit. So, yeah, so appetite. seems to be related to how much weight people are losing. And so that's one of the reasons why I think it's important to kind of not have this zero interest bank account analogy, because what's happening when people are trying to change their lifestyle to lose weight is that they have this dynamic effect on metabolism, it's not as big as your previous guests have suggested it is to prevent. And in fact, the bigger effect is the increase in appetite, which is, again, in proportion to weight

loss. And we come up with some numbers about this. So roughly speaking, for every kilo of weight that you lose, your body's overall calorie expenditure will go down by about 25 calories per day. So you lose like, you know, 20 pounds or so. You're looking at 250 calories per day less energy expenditure to maintain that lower weight. Appetite, on the other hand, goes up by about 95 calories per day, above baseline for every kilogram of weight that you lose. So the appetite control side of the equation is much more powerful in determining where you're going to plateau, how much weight you're going to lose, and how hard you're working constantly, even after you've plateaued, right? Because you're fighting a greater and greater battle in terms of your

appetite, the more weight that you lose. And you're also burning fewer calories. But that's the minority of things. It's the appetite control piece that I think is the really important fact. And so I think it's no accident that these most successful weight loss drugs on the market are really focused primarily on on changing people's appetite by mechanisms that are, again, still not fully understood. So yeah, so working, so that's how calorie in, calorie out really works. It's this dynamic phenomenon. And it's not the zero interest bank account. So from that perspective, they're completely right. Now, the other question is, what is driving those appetite changes? What's driving the changes in calorie expenditure? And oftentimes people will say,

well, it's hormones, right? And yeah, some hormones can play a role. Oversimplification. Yeah, they certainly can, right? And there are some people who, yeah, have obesity because, you know, they're hypothyroid or something like that. But they're the minority of folks. And what, again, some of these folks have focused on, they'll say, okay, well, let's just take a more basic approach and they come up with a very compelling sounding story, which is that, well, what is it that drives accumulation of fat inside fat cells? Well, at the level of the fat cell, it's seeing these hormones. And one of the hormones that's involved is insulin. We've known from basic endocrinology for decades and decades

that insulin slows the release of fat from fat cells. It also stimulates the uptake of fatty acids from triglycerides that are circulating in the blood, stimulates production of fat from carbohydrates in a process called de novo lipogenesis. And so from the level of the fat cell, maybe insulin is a big player, and it is a big player. Is it the only player? No, it's not the only player. But they ignore that other side because they're building us case here.

They're building a story. And the story goes that, okay, well, if insulin has this major role, then what drives insulin? Well, glucose in the blood drives insulin. What drives glucose in the blood? Carbs in the diet drive glucose in the blood. And so if you're eating a very high carbohydrate diet, you'll drive up insulin levels,

and that will tend to promote storage of fat and fat cells. And every one of those, yeah, there's evidence behind every single one. And then they might be oversimplified. There are other things playing a role, like triglycerides in the blood also slow. release of fat from fat cells and stimulate uptake of fat. But then we're going to ignore that. And fat can be direct, dietary fat can be directly absorbed.

Well, it's not directly absorbed. Meaning stored. It can be stored, right? But the point is, is that people focus mostly on insulin in its role there. And there have been really interesting experiments done by Keith Frayne at Oxford when he was active. He's retired now. But he's done these really remarkable studies where he keeps insulin constant and infuses

lipid emulsion that has these triglycerides and he measures the same processes of how much fat is being released from adipose tissue the fat tissue and how much is being taken up and triglyceride molecules themselves especially dietary triglycerides from chylomicrons also inhibit lipolysis as potently as insulin and they also stimulate the uptake of fat from those triglyceride molecules themselves so the body he has lots of ways of getting those calories stored inside fat cells. But again, those are only a few pieces of data. We need to better understand that process.

We don't understand it nearly as well as we understand the role of insulin in regulation of fat storage and fat tissue. There's lots of really interesting research that should go on there. But it's been demonstrated to hold. And so the story then goes, well, if the calories are being stored in fat tissue, because you're eating too many carbs that are causing these spikes in insulin, then that's going to starve the rest of the body of fuels, which is going to make you hungrier and it's going to slow down your metabolic rate.

That's a really interesting theory, right? I mean, it's kind of turning the causality on its head in terms of, oh, well, you're just overeating calories and you're too sedentary, and that's the reason you're storing all these calories in fat tissue. This kind of makes a compelling case that, no, actually, the hormonal meal you because of the diet that I'm eating is what's storing the calories and the fat tissue and I'm only overeating because of my fat tissue expanding and keeping those calories. And so it's a really compelling story and people have made that story and modified

it over the years in various different ways. And we've designed studies to try to test that and we don't see all of those pieces of the puzzle kind of coming together in that way. It doesn't mean it's wrong. It's just incomplete. It's incomplete. And are there other theories that are out there that are perhaps more compelling? We kind of hold to another theory that we think is a little bit more compelling, happy to be wrong, but you have to design the right to experiments to kind of test these competing

theories. And I think everybody agrees on that. What's the other theory that you're... So it has a terrible name. I don't think it's the right name. It's called the energy balance model. It's what you would... I think you were alluding to as...

calories in calories out. But I think the point is that it's not the simple zero interest bank account model. It's the model that says, yes, the body sends the brain signals all the time about what its needs are. Hormones play a role. The nervous system itself plays a role. Who knows the gut microbiome may play a role. The different tissues and their energy states may play a role. Clearly, we have to have this in order to grow an organism, right? If you have to modify the composition of a growing body, the body has to send the signal somehow of what its needs are. But the environment that we find ourselves in also plays a role. We're seeing what the availability of food is. We're learning about food in our environment and our social interactions and what's

available to us versus what's kind of aspirational, what kind of time constraints we have, the social pressures, all these broader things that we call the food environment. And that those two things, the internal signals and these external factors of the food environment are being integrated in our brains in very complicated ways that we clearly don't fully understand right now. But it's that integration of those two facts. So in your analogy of the bank account? We're not factoring in the interest when we do calories in calories out exclusively. Does the interest represent behavior?

Is that all encompassing from an intrinsic and extrinsic viewpoint of what could be happening? Yeah, no, I mean, I think this is where the bank account thing falls apart, right? Because what your social environment is, is how much you can put into the or withdraw from the bank account, right? So these extraneous factors, in addition to you're monitoring what's happening inside the bank account itself to, to redistribute your funds into different place. Yeah, maybe you could stretch the analogy to its breaking point. But the point is that our bodies have evolved in such a way that we're listening to our bodies. We're listening to what's in our environment and we're integrating that in a very complicated way that we're only beginning to work out.

At the end of the day, yes, there are things that are called laws of conservation of energy, which I think is what a lot of folks in the calories in calories out camp will harp on. but the determinants of why is it that we choose to eat the way that we choose to eat and given social situations and given our backgrounds in our economic environment and what is it our bodies are telling us that we should be eating and how does that modified by the foods themselves right that complicated interaction is what you know I think we need a lot more research to figure out yeah I to defend the calories in calories out folks, I don't think they disbelieve that fact. Okay.

I think a lot of them believe that, but it feels like to them, the people who are in other groups just discount at baseline, the calories in calories out model. Okay. So to them, it's like, no, no, no, that just doesn't exist. And it's, no, no, it exists. And then there's all these other factors that play. So at least that's the way I've seen a play out on the social media sphere. Can you know, I would love to, but the fact is I feel like,

whenever they're presented with data that's conflicting, instead of explaining, yeah, it's complex and there's other factors, they try to shed some sort of shade on the research that was. Well, let me push back a little bit on that. I think that they are unfair in a certain extent, but they're also doing something which is rational in another way. Because what they do is they say, okay, Kevin Hall, you did this experiment, seems to suggest that the carbon slim model isn't giving the predictions

that the data suggest, well, you just haven't looked long enough and you haven't done the right experiment. And they would say that one way to say that is that they're throwing shade on the studies and they're throwing shade on my motivations for doing the studies. And there's probably a part of that. But there's also the unspoken fact, which was, look, the basis of the carbohydrate insulin model was all short-term studies on how insulin affects adipose tissue. What you've just done is you've modified your own model.

And you've modified it in a way that you haven't admitted to modifying it. But you've said, oh, actually, yeah, it probably plays out in a little bit longer time scale. And you weren't able to detect it in that experiment. If they were very open about that, I would be like, okay, cool. We can work together, right? But they're not. Some of them are. I mean, some are, but then others will try and find the holes and find lean mass hyper responders as the outlier group or what have you.

It's always something wrong in order to prove. And I don't know why there's this, like it almost became a church or a religion to them. Yeah. And I don't get that. Yeah. I mean, but to be fair, I see exactly the same thing on the opposite side. Like I said, the McDougal camp of folks. I mean, he's, what at the McDougal?

So John McDowell, he's passed away, sadly now. He's a very nice guy and very enthusiastic about my research. But he was a low-fat vegan proponent. Got it. And he saw in our research and what and how the low carb community had responded to our research. And he was very enthusiastic invited me to give talks to his, to his followers and got me connected with some other folks who are vegan advocates and I would go give talks to them. And I remember one day after one of McDougal's advanced study workshops in California,

I was a very similar setting to here. He brought me in for an interview afterwards. And he wanted me to say that, you know, yeah, the low-carb diets are horrible for you. Yeah, low-fat vegan is the way to go. And isn't your research really showing? I just, I couldn't. I'm like, you know, I think our research is interesting. I think it's really interesting, but I don't think it's saying what you think it's saying.

And maybe I'm wrong. But we need to do more research that's more practical. If those are the practical questions that you're interested, I'm, I sort of view myself more as a physiologist who's interested in how the body responds and working out what these appetite circuits are and how the foods in our food environment are driving excess calorie intake and how we can redesign our food environment to actually prevent that. So those are practical questions, but I don't design practical studies that are necessarily translatable in the way that many physicians want me to translate those studies. Although I venture to say,

while we don't know the exact mechanistic reason for the ultra-processed food group to gain more weight or consume more food, to me, that's practical enough data for me to recommend to my patients to limit ultra-processed foods. So what if I told you, and I presented this data in November in London, the interim analysis of our current study is that we were able to design a diet that also had 80% of calories from ultra-processed food, and people did not gain weight. I would take away, and this is speculative because I don't know the research, I would venture to say that the people on a practical level in the United States are consuming American standard

diet are not consuming the ultra-processed foods that you would be pre-selecting for that study. Yeah, I mean, that might be true. I guess the question is, can we use the knowledge about how we design that diet to give both consumers advice of, look, ultra-processed foods just because they're ultra-processed doesn't mean that they're necessarily unhealthy for you. Many of them are. What are the mechanisms? And if we could understand the mechanisms,

then we would be able to tell our policy folks, are people who do regulation. Without a doubt. But I need to tell my patient something. Yeah, yeah. And it's like almost, you know, when you're teaching first grade math, I don't know if it's the right class

where they teach math, and they say, oh, no, you can't subtract five from two. Because negative numbers don't exist. But it's valuable to teach them that. Sure, of course. So in the same way that I have a limited amount of time with my patient, I need to make some impact on their life, largely the assumption that they're consuming ultra-processed foods that are driving their weight gain based on the knowledge I know now will help them.

Do I know the mechanism? Can I be 100% sure? It feels like it's the best advice I can give. So here's the potential problem with that, is that ultra-processed foods by design are convenient. They can be incorporated into your life. They're inexpensive. They don't require a lot of skill and equipment to prepare or store. And if you have the privilege of being able to avoid them, I'm not going to stand in your way.

I think that, yes, you could do Michael Pollan's advice of eat food and what he means is avoid ultra-processed foods. Or increase whole foods. And not too much. Yeah. And in fact, that's how we did it in our ultra-process food. And that's where you saw the best outcomes from a CRP model, for example. Well, in that case, we avoided all ultra-processed foods, but the way that we designed a diet that was still 80% of calories from ultra-processed foods, but lead that did not lead to weight gain is that we chose ultra-processed foods and combine them with fresh whole foods or even frozen whole foods that reduced the energy density of the diet. We chose ultra-processed foods that weren't hyper-palatable by that Terrafezino's definition. And again, people were rating them.

the meals is equally pleasant, they just weren't overeating them. But my point is that if an ultra-processed pasta sauce or salad dressing makes it a lot easier for you to make a salad and make pasta that that's healthy for you and add some vegetables to that, then that should be encouraged, even though the overall meal is going to be labeled as mostly ultra-processed. I agree in the future. This is a great reality for us to come to. I just don't feel like that's the reality for most.

most these days. I don't think most people, if we survey the American standard diet, if we see what percentage that they're consuming ultra-processed foods. You're absolutely right. But I think if we take this very broad category, right, which is a huge category. Right. The definition by which is not speculative. Yeah, I mean, it's a, it's a reasonable first step, right? And I think that what I would like to introduce is the concept that there are probably healthy ultra-process foods. Right. And there's a bunch that are probably neutral for health. And then there's a fraction that are driving most of the problems. And I think what you're pointing out is that the ones that are driving most of the problems

are often the ones that are most heavily marketed. They're available everywhere. They're also convenient, tasty, and shelf stable and are the ones that most people have access to. And lobbyists are fighting for subsidies for. Yeah. So I think that that's the, and there I'm totally on board with you. But what I would love to see is the kind of promotion of the health, varieties. That would be amazing, yeah. And what sort of policies can we put in place?

Which is where we are today. Yeah. In a very bad position because, you know, the last hour and a half or so, you've pointed out all the amazing work you've done, the intricacies, the fact that you're always questioning your own work, even questioning others' interpretation of your own work, even though it could be beneficial to you. So A, I applaud you for that. B, we need to celebrate individuals like yourself who are willing to do this work, because not everyone is, people oftentimes get married to ideas as researchers, and you're still trying to keep the most practical mindset to try and help the biggest number of people. Bank more oncores when you switch to a Scotia Bank banking package.

Learn more at scotia bank.com slash banking packages. Conditions apply. Scotia Bank, you're richer than you think. currently we have people in the healthcare space secretary kennedy has this maha movement make america healthy again he frequently speaks on the amount of chronic health conditions we have in the u.s that it's a rising number obesity is a rising number frequently targeting ultra processed foods you have to be his hero i mean like if based on that notion of secretary kelly there has to be a photo of you hanging up in his office. Does it have a dartboard behind? No, but like you, if I'm truly wanting to solve all those problems, like I would be calling

you every day to try and solve these problems. Is that happening? Um, no, not at all. Um, you know, it was interesting, like, I may or may not have mentioned, you know, nutrition science and the kind of work that we've been doing has had dwindling support for a very long period of time. back in the 2010s, the NIH defunded the clinical research centers across the country that were, that had the facilities to do the kinds of work that we'd been doing at the NIH. And so the kinds of controlled feeding studies that we were doing and the investigation of the causes of metabolic disease just dropped like a rock.

People wrote eulogies in the journal Diabetes. My friend Mike Jensen wrote a eulogy for the clinical metabolic investigator. And I don't know the answer to that question. I think that there's always been a stigma to nutrition science. It was in the home economics department in many universities. It was dominated by women for a very long period of time. And I don't know if there's a sexism involved in that. It was always a soft science.

I'm not sure. I don't really know the answer. It's just strange because we're seeing a curve go up with chronic health conditions related to nutrition. and there were secretion research. Right. Well, I mean, to be fair, and I think this is, again, one of the messages that is probably accurate,

and James Tabori did a really interesting book called The Tyranny of the Gene, which is about this idea of, you know, the NIH has focused on treatment of disease looking for, genetic underpinnings, precision medicine. A huge chunk of money has gone to those kinds of things and has devalued environmental causes. and better understanding how environmental exposures contribute to the rise of many of these

kinds of chronic disease. And so, and similarly, I think metabolic disease and obesity in particular has had stigma and continues to have stigma where many folks just think, oh, people with obesity just lack willpower. And here's just the gluttony and sloth idea of original sins. and in fact, you know, when I was doing my research many, many years ago, I would get, and I would study people with obesity and insulin resistance because I'm not a physician, I would not study people with type 2 diabetes typically.

When I started to think about studying folks with specific medical conditions, I was told, oh, I'm great that you would study people with disease. I'm like, decade before, the NIH was one of the first to come out and say obesity is a disease. But even at the NIH, the higher-ups didn't consider obesity as a disease. And we're saying, well, why don't you study people with a disease? I'm like, yeah, I am. Is that just medical inertia from? Probably.

Who knows? But then there was a period of time they actually tried to close our metabolic ward. In fact, that happened right after our ultra-processed food paper got all this media attention. And I don't want to take credit for the fact that we didn't close. But, you know, I kind of went outside my lane and found somebody. higher up in the Health and Human Services Department, who I knew had read our paper and thought it was really interesting. After I was told that I should have no confidence, I'll still be able to continue my research

after our unit closes by a leader at the NIH. I'm like, okay, I got nothing to lose. And I talked to this guy and said, well, you know, they're proposing closing our research facilities and it'd be really tragic because we'd never figure out what it is about ultra-process foods that are driving the effects that you know you're so interested in and um and with some other pushback from some outside organizations we were able to prevent the closure but they actually still took um 30 percent of the beds from the from our unit and that slowed our studies to a crawl so there's been this kind of stigma against nutrition research against these

highly controlled metabolic studies that's been in existence for years and so you must have an ecstatic hearing that secretary county was coming in excited about nutrition well i mean it went even before that right i mean to be fair it was a bipartisan thing right so corey booker and bernie sanders were just as vocal about you know diet related chronic disease and ultra-processed foods and better understanding you know the these conditions that are now costing americans so much suffering and so much economically as well um not to mention you know medicare spending and Medicaid. And so there really was this movement of folks on both sides of the aisle. And even when Kennedy was running as an independent, you know, the Maha movement was really getting

started. And you couldn't tell the difference between what Robert F. Kennedy Jr. was saying about food and Bernie Sanders was saying about food and the role of the food industry and marketing and creating these foods and pushing them. And so I was thinking, yeah, this might be, not only could, you know, we'd prevent further closure of our, of our research, but we have to start really thinking about no matter what happens in this election, how are we going to actually expand our research? How are we going to actually provide scientists outside the NIH with the kind of facilities that would allow us to supercharge this kind of research so that we could instead of having a hypothesis and then three years later being able to answer it? How can we do that in months? And it really came down to this issue of, well, we just don't have the capacity

to comfortably house and feed people and measure what they're eating and control their food environment. And by food environment, in our case, it's very artificial. We could do other things like have a little marketplace where we manipulate the prices of foods. We could have a restaurant where we change the menu labels as well as lots of behavioral science aspects

as well as just really the basic metabolic effects of these foods. So we put together a proposal that no matter who was going to be in office, we were going to start to try to pitch. And I worked on this with the director of the Office of Nutrition Research at the NIH, my colleagues in the diabetes endocrinology and obesity branch in the diabetes institute got input from several other people. And we're kind of putting together like what would we need to do to really supersize this? and as well as kind of demonstrate that if we could understand these things better, then we could actually make real changes. Like I said, we had that interim analysis in November where we suggested,

if we understood the mechanisms, we could create a diet that was still high in ultra-processed foods that doesn't cause overeating. And that could give policymakers as well as manufacturers and regulators the kind of information as well as consumers to make changes, practical changes in their diet. So, yes, I was super excited. And then the election turned out this way. And it was clear that by that point, you know, the Republicans and RFK Jr. were talking more about this than Kamala Harris was talking about it. So I was like, okay, well, you know, let's try to engage the folks who are leaders in the Maha movement at the political level.

I know there's a grassroots level, which is not necessarily thrilled with many of the things that are going on now. But at the political level, you know, we can hopefully get some, get some space to have some conversations about it. So I reached out to some folks multiple times. I got a couple like DMs back saying, oh yeah, let's send me an email and sent him an email. It's like, okay, I know you're really busy with no response. A few weeks later, send another email. It's like, yeah, I really still love to talk, no response. Jeez, this is weird. And then you see that they're engaging all a time with these social media influencers, right, of like who talk a lot about things which, you know, I didn't see as being the top of the list of problems that we should be focusing on,

like food dies. You know, changing the color of fruit loops is not going to make fruit loops a health food, right? Changing from high fructose corn syrup to cane sugar and Coca-Cola is not can make me want to promote Coca-Cola products as healthy products. So, you know, maybe that's just the window dressing, the low-hanging fruit. I would hope so. But I didn't see a lot of engagement. They certainly were ignoring me, right? And then we, maybe it was the transition period.

At first, it was like, okay, no, you can't talk to outside people. You're not allowed to give talks at conferences. This was across the board for a period of time. When that was starting to, and to be fair, that happened in the Obama transition. I think it lasted for a few days as the new administration came. That's within reason, I guess. Yeah, I guess. I mean, they just kind of wanted to vet what was coming down the pike and whatnot.

I don't know what the real reasons for these things are. But this lasted a little bit longer. And then eventually it was that some areas of research you could start. maybe you couldn't practically travel, but you could at least give a talk virtually at a conference. And I had an invitation from the Bloomberg Philanthropies group in their yearly summit on health and food. And they invited me to talk about ultra-process food. And I said, well, you know, I have to put it through the normal process. I'd be delighted to do this, but it has to pass through the NIH.

What I learned was that there were certain topics that were deemed politically of interest, a bunch on diversity and health equity, nutrition and ultra-processed food was on the list. Meaning like censorship, you're not allowed to talk about those things? No, no, meaning that at that point it was like anything that was flagged internally at the NIH that was on these topics had to be approved by a political appointee. And so my request went up the chain and it was denied. I wasn't allowed to give this talk. And I'm like, okay, was it just the travel thing? Because we had to worry about travel stuff separately than these other things. And I went back to the Bloomberg folks and we'd be delighted for you to do it virtually.

Same response. And this is meanwhile, now some of my colleagues are able to give talks on other topics, but not on ultra-processed foods. So that was, and this is now, you know, many, many weeks into this, into this, to this new administration. I wasn't allowed to give a talk about our research, which I never had that in my entire history of 21 years at the NIH. I've always been allowed to talk about our research at conferences and meetings like this. So, and then there was, I'd been working on a paper with a bunch of researchers. I don't know if it's out yet. It was with the American Heart Association working on consensus statement on ultra-processed foods.

It had lots of different pieces to it. There was one piece written by a colleague of mine who wrote about health equity aspects and how these foods are sometimes targeted to communities that are, you know, have low-so. Exactly. And then I wrote some of the section on proposed mechanisms by which ultra-processed foods work. And again, the normal process is you submit your manuscript. It gets cleared and it goes off and gets published. And in this case, it actually cleared and then it was unclear.

Okay. I'm like, how do they notify you that it's clear than unclear? Like they send you an email so you're good? Yeah, because I got an email saying, yep, we're good to go. Just submit the paper. And I wrote to my colleagues. I'm like, yeah, we're good. Go ahead and submit.

And then I got the unclear, I'm like, whoa, wait a second. I'm not sure what's happening. And I was told, and this is the level of the NIH, was that there was an executive order about health equity and certain language around health equity that's prohibited. And so if you want to remain an author on this paper, you've got to address the section of the paper on health equity. I'd dress to, like, remove it?

That could have been an option. that probably would have satisfied their concerns. I didn't want to press it because I'm not willing to... It's not your part either. I'm not willing to censor my colleague, right? I mean, this is complete and total nonsense. And so I'm like, fine, I'm off.

I'm off as an author. And, of course, everyone was like, oh, well, maybe we could, you know, try this. I'm like, no, we should not change the wording to satisfy this kind of level of censorship of what's a legitimate scientific question about how different, different groups in this country who have health disparities are being

differentially targeted by marketing schemes and whatnot it's a perfectly legitimate thing it's not my area but it should not be edited right so that was the second piece and then we had a really I was really excited about this piece of research conducted by a you know superstar postdoc in my lab who actually now has a tenure track position at and I where we were addressing the question about whether or not ultra-processed foods high in fat and sugar can cause the same kind of changes in the brain's dopamine response as highly addictive drugs because there's all this rhetoric about sugars as addictive as cocaine and and from our colleagues

in the addiction institute there's been a really interesting progress in understanding the biochemical mechanisms, or at least correlates of addiction. And one of them is that drugs that are highly addictive, many of them give rise to this supersized dopamine response in brain reward regions, which hijack them. And over time, you build up a tolerance and changes in the receptor numbers in the brain. But initially in the early phases, you should be able to detect a big change in dopamine. And then people who become addicted or develop tolerance, you'll be able to see it gets downregulated the receptors and even the response.

So we designed this big study looking at 50 people with a very wide range of BMI. The idea was if people with obesity are addicted to ultra-process foods high in fat and sugar in the same way that people that are addicted to cocaine, then the more fat you have on your body. the lower your dopamine response should be to eating the ultra-process food in the same way that the addicted person taking the cocaine is going to have a lower response than a person who's not addicted and so we designed a study to test that effect and it was a large study because we're now looking at for a correlation between body fat and the dopamine release and we presumed we were going to see a dopamine release when we gave these kinds of foods because really small studies in the past had shown it and we like were taken in by the rhetoric that you We're going to see the dopamine. We kind of presumed we would see it. And when we looked at the data, we didn't see, on average, any dopamine response that was measurable using the same techniques that our colleagues in the addiction.

So it's not that there wasn't a change. There was no response. Well, the methods that are being used have relatively low sensitivity. So you have to see a really big response in order to measure it reliably. And yeah, when you give cocaine, methamphetamine, even nicotine. in many studies. You can see this response. And we presumed you'd see it with food. And in fact, other people had shown it with food. But then when we look back at those other things, they were so tiny and it was driven by only a couple of outliers. And studies weren't really designed to test

this idea. And so we kind of think that maybe they were underpowered. And it was like a false positive. Because when we did it in a much, much larger group of subjects, there's a lot of variability. So some people respond. Some people don't respond. But on average, there was no mean change in dopamine in the reward regions of their brain. And there was no relationship even with that variability with adiposity or BMI. So it was interesting. Our conclusion was not that there's no dopamine response. It's just lower than these drugs, right? Yeah, exactly. Maybe it's an opioid response. Maybe it's something else. Maybe there really are people who are addicted to food in similar ways, but we didn't. The pathway is not unknown yet.

The Pathways Unknown, or maybe we recruited the wrong folks in this particular study, it had all that nuance associated with it. And this was a study that ran over COVID. Like, it was a huge amount of work to do this. And so we put together, we'd had a press release already. And this was now the transition period. The paper was already accepted. It was coming out in the next several weeks.

And we were saying, yeah, no press release. This was now, again, at the level above NIH, because of it. all ultra-processed food stuff was being evaluated by a political appointee and we're okay maybe we can put together not a press release which had quotes from us and maybe we'll just put what they called a media advisory which is like just a very short paragraph saying this paper's coming out no quotes denied none of that so we're like okay this is really weird and and so but the journal puts out it was part of their special issue on obesity they put out their notification to journalists.

One of them from the New York Times says that they're really interested in interviewing me about the paper. And so we do the usual thing. I put it to our media office to get approval. And then I hear, yeah, HHS isn't approving this interview. And this reporter had interviewed me many times in the past. And she's like, what's going on? This is really weird.

Like, is there a reason I'm not giving the chance to interview? done this many times before, were you not happy about, like, the way the articles turned out? Did I, did I do a hack job of the study? Like, what's going on? And it turned out then she told me she got a call from the Health and Human Services Communications Director who asked if this was really an article about RFK Jr. because the results of the study don't support his views on ultra-processed food. And that was my reaction. like, wait a second. So the concern is that the concern is that this isn't really about the science,

this interview is about somehow saying that the science doesn't agree with, first of all, I don't know that it disagrees. I don't know what RFK's juniors are ultra-processed foods. And certainly I didn't think that my study had anything to say about that these foods might be addictive and many people, be harmful. You were looking at a me.

Exactly. I'm like, what, what's going on? And, and, and, and, and then I'm like, okay, this is really weird. And apparently in that discussion, she convinced him this isn't, you know, she was going to talk about how she wasn't going to be able to interview me. That was the only thing that would be weird about the, about, about the piece that she was writing. But it really was about our ultra-process foods addictive and what does this new study say and how does it relate to what other folks are saying. And so I guess she got permission to give written questions. So we got her written questions and me and my co-author, we wrote our responses and we got some input from the Addiction Institute because it was obviously related to addiction and we worked those responses together. And I said, okay, well, here's, here are our responses and submitted them to our press office. And then the next day I got C-Ced on the email back to the reporter from the press office. and the responses had been edited. And they were downplaying our study. They were saying, in response to I think the question was, what's the most important takeaway from the study?

This is clearly not something I would have written. This was a very small study and a limited number of ultrapros. It's like, yeah, I'm fully aware of all the limitations. We have another paragraph about that lower down. That's not the most important takeaway that this was a small study. In fact, this is the largest study of its kind that had ever been done. done. And there were other edits throughout this to really try to downplay, you know, whether or not these results have anything to say about ultra-processed foods. I mean, that's unprecedented.

Yeah, I couldn't believe it. And, you know, I think it was characterized as censorship, but when I talked to folks afterwards, but it's worse than censorship, right? I mean, they're literally, they signed my name to something. And it was funny because Alice, the journalist, then wrote back and said, oh, who do we attribute these responses to? And the media folks called me, like, frantically, like, okay, what am I supposed to say? I'm like, my advice to you, because you know these were edited, is you don't respond to this email because clearly either you're going to lie to them and say that whoever edited, I have no idea who edited them.

I'm guessing it's probably the HHS Communications Director or at his direction. They were edited because he was the one who expressed concerns about the piece and said that they didn't agree with RFK Jr's views on ultra-processed foods, which was news to me. Or you're going to have to say who edited them. And I don't envy you in either situation. So I suggest you just don't respond to the query. And of course, I made sure that the reporter knew that it was. Knew that what our original answers were.

And when she quoted from them, she only quoted from the parts. that we had answered, not the edited version. But yeah, this was so concerning to me now because not only were we not able to give talks, not only were we not able to publish our papers in the normal way, but now they're manipulating the way that we communicate our results to the public.

And I was really concerned that, well, what about... And not for any good reason. They're not saying, oh, this is complex science speak. We're trying to translate. They're literally changing... how data should be interpreted based on the fact that it disagrees with someone's opinion. Right. And, you know, I would have even been open to a discussion about it, right? Right. Like, call me and tell me why you don't like our responses.

Right. And I can argue about it. And yeah, I can still tell you you're full of shit. But at least engage me in this exercise. That did not happen. I've had no direct communications with the folks at HHS ever. And so, yeah, it was just like crazy. And so what I'm worried about at this point is that, okay, if they didn't like the reporting of the study results, I've got this other study, like I said, that's just, you know, we're going to wrap up very, very soon. What if they, and this case, the paper was accepted already, right? What's it going to be like when I now submit, I've already got the precedent of it not being released to be submitted for peer review, right? I had to remove myself as an author from that other paper. What about now my main paper, if they don't like the messaging around the results,

are they going to try to manipulate the way the paper is written? That's unacceptable to me. And what about a new study I want to design? Are they going to manipulate the way that the study is designed in a way that's going to potentially give rise to the result that they want? And more concerningly, it suggested to me that they're not interested in what the science has to say. If it complicates their narrative that ultra-processed foods are as addictive as cocaine and work by the same mechanism, who cares about that from a practical standpoint, from a

scientific standpoint, it's important, then that's a huge problem. If the premier biomedical research organization in the world is no longer interested in communicating science, that's That's the genuine fear because it might interfere with a preconceived narrative. Which is the exact opposite of what research is. Research like you were saying at the beginning of our conversation, you would be excited to learn something if it disagreed with your preconceived notions. They, on the other hand, don't want to hear disagreement. They want to hear confirmation only.

Right. And I can see how, I mean, science has a way of introducing complexity and nuance when it's done right in a way that complicates things. I get that. And if you want to move fast and break things and just kind of get something done, I could understand why it would be inconvenient to have that science. And if I thought that they were doing all the right things, you know, maybe I could be more forgiving of, you know, okay, well, yeah,

let's suppress some of the inconvenient stuff for a while or downplay it. But we're not going to manipulate your studies. If they come back and say, okay, look, just, you know, maybe. This one press release. Press release, because it wasn't done with us on board, et cetera. You were being reasonable. I was hoping to be reasonable, yeah. And so I actually then wrote to RFK Jr., several of his deputies,

because who knows who's reading these things, Jay Batachari, Matt Memley, and other folks at NIH, and just kind of said, look, and this is right around the time they're starting to fire people. They set up all these programs to get people to leave voluntarily, in one of those programs was voluntary early retirement. And what they do is basically retirement from the federal government has one huge benefit, which is you get to keep your health insurance for your family.

I'm Canadian originally. It would normally seem like a big benefit, but it's a huge benefit, right? Because health insurance is extraordinarily expensive. And if you can get health insurance for life, that's a big benefit. And they made that available to people. They dropped the retirement age to 50, I'm 54, and you had to have 20 years of service. I had 21 years of service. And I thought, look, I'm either going to hate my job every day if my worst fear has turned out to be true,

in which case I'm going to quit, I'm going to lose my health insurance. And it's going to be a huge problem. Or I can take early retirement and preserve my health insurance. or I can try to convince somebody to sit down and talk with me and tell me why I'm misled and misguided by this. And so I wrote this email to all these senior folks at HHS and NIH saying, look, here's what we're doing some of the world's leading research on ultra-process foods and trying to figure out why many of them are bad for us and what we can do about it.

We're having a lot of success. We're conducting the premier research in the world. I kind of pointed out some of the interim results and how that might be effective for policy. I said how excited I am about the Maha movement, right? This group of folks across the country, this grassroots initiative that has finally made diet-related chronic disease, put it on the map of what's a super important thing to solve. And the fact that we actually have, I submitted a proposal and they've been working with folks at NIH about how to provide the kind of facility. for researchers around the country to conduct studies that are much better than the ones that I'm currently able to conduct and get answers much more quickly.

But here's my concern. My concern is that I'm getting censored and that you're not interested in the science and manipulating the communications to the public. And I'd love to sit down and talk with you about this and why I just might have all this wrong. And I really hope I do have it all wrong. But otherwise, I don't see any way forward. And by the way, while all this is happening, we're having troubles buying food for our participants

because of the stuff that they're doing with purchasing and purchasing agents getting fired. We're having troubles buying supplies for our studies. We haven't been able to use CGMs for a long time because we haven't been able to purchase them. We had a period of time where these wonderful recent undergraduates who do the vast amount of the legwork and the study coordination and whatnot, we weren't able to replace them for a period of time. I think that's finally lifted, but it was bleak, like super bleak. And the leadership of our institute and the intramural side of NIH told me, yeah, we don't see this getting any better.

And it's only going to get worse when they start to try to consolidate institutes and change the organizational structure. Right. So I'm like, gosh, this is really horrible. I want to sit down and talk to some folks about this. And at least find out the plan. found out the plan, you know, what is the plan, and how can we actually do something good, at least in the midst of all this chaos and destruction?

What did you hear back? I heard nothing. And I know that someone read my email because the Office of Nutrition Research Director said, hey, yeah, I saw your email. Like, I didn't send it to you. And she says, no, no, no, the NIH director's office sent it around to a bunch of people. Just kind of as an FYI. I'm like, oh, well, someone read it and bothered to send it around to a bunch of people in NIH,

but they didn't bother to respond to me. So I basically started the process, a week's long process of having my staff reassigned, assigning my protocols to other people, closing down a lab that I'd had for 21 years at the NIH. And yeah, it kind of ended one day in April and I gave, I had instructions of where to put my badge and my parking pass and my office key and it cleaned out all of my desk. And yeah, it was a very, very sad day. I mean, I loved my job. I mean, this was a place I'd spent 21 years at. I mean, I took a pay cut to go there.

I came from that biotech company. We had lots of freedom that I told you about the kind of support that I had in our institute, despite, you know, some struggles along the way, this was, you know, my dream job. And I thought we were starting to make a difference. I thought we had all this amazing opportunity to really expand on it and give folks around the country the kinds of facilities that we had had access to only on a greater scale to really improve nutrition science, which has been chronically underfunded, like I said. so yeah so it was very sad day and and i posted on social media and um it got a little bit of

press attention understatement and uh and then the next day i got a DM from j baticharia the NIH director on x saying oh i heard about your retirement oh now you've now you've heard about it and i sort of it's a very media focus administration yeah right that's that's that's that's probably true. If you're on the news and I was in the news, then you might get some attention. And so I said, y'all, I'm delighted to hear from you. You know, I'd love to talk. And he invited me back to the NIH campus the next day. And yeah, it was really interesting. I was first time as a visitor at the NIH since I interviewed 22 years prior or so. And, and, you know, you know, thought you might be able to go back well i didn't know i had no idea at that point right i mean i

i left i didn't have a lab so there's nothing to go back to um my staff had all been reassigned by protocols had been reassigned and um you know basically closed um i've been able to what were your colleagues saying um yeah so it was interesting i mean some of them were especially after the media attention, they were actually really heartened by the fact that there was such an outpouring of support. Because up until that point, it'd just been bleak and seeing colleagues fired. And by the way, all the press office folks that dealt with all of the stuff, they'd all been fired. And so, you know, several of them were just very supportive and they were delighted that it was getting some attention in the public that

basically there was kind of destruction of the biomedical research enterprise going on. And even something as high profile as ultra-processed foods that were obviously the huge Maha movement was based around much of that was part of the momentum and much discussion about it that even in that kind of space where everyone would have expected there to be all this support, we weren't getting it. And so, so yeah, so anyway, I got the chance to meet with J. Badacharya and the deputy director for intramural research at the NIH who was like my, at the top of the food chain of the intramural side, which was where I was at the NIH the next day. And, and it was clear that Jay Batachari wanted to talk about the censorship thing most of the time and because he feels like he was censored during COVID and he has a deep personal sort of

experience about that and and he was also kind of shocked about the usual process that we've had for decades and decades of having to have manuscripts cleared right before but I was like yeah that's never been a problem before and I can even understand maybe why there's a hiccup with that but what about this editing of the responses and he kind of didn't believe me at first I kind of showed him some signal screenshot so here's what happened and he was like he kind of didn't really and he was like oh well maybe this was all just sort of you know a miscommunication or something I'm like that'd be great if it was but then why didn't anyone respond when I tried to reach out even before the election right I mean yeah you know why why is no one engaging in this

and he said you know well he's not sure and he thinks that there's things that he wants to do at NIH to improve the ability for people to have opposing viewpoints. And he said all the right things. And I kind of shifted to the question of, well, look, there's all this destruction going on. One of the things that I proposed in that email that is about how to improve, like how can you build something, how to improve nutrition science. And it would clear that he'd read the document. And he'd even read the transition plan because He said, oh, yeah, I saw that the clinical center has a really low census right now. Maybe we could expand beds for your facility while we built something else.

And I said, yeah, that would be amazing. He said, well, yeah, I'd like to work on this with you. And he shook my hand and he said, welcome back. I said, well, I'm not back yet. I don't have anything to come back to, but I'd be delighted to work on this new initiative. And he said, okay, well, talk to the deputy director here and we'll figure out way for whether we can do this. And so for the next weeks, you know, I worked with the Office of Nutrition Research Director and the Deputy Director for Intramural Research and other folks. And

it was presented in a couple of other meetings, not that I wasn't a part of. And I got, you know, feedback that was pretty glowing. And everyone was really on board and excited about this possibility. So I thought I was going to go back. And I made it very clear. Like, I would love to come back. before I retired, I checked with human resources. Can I come back and work full time? And like a triple check. And I was like, yeah, you can do that. It's not a problem. And so I was getting very excited that we would finally be able to kind of achieve something and be able to get rapid answers to the kinds of questions that many of the folks in the Maha movement have been begging for answers to for quite some time and at least improve the quality of the evidence on these things. And then a couple of weeks into this, many back and forth. We were talking to the foundation for NIH about raising money for this, all sorts of stuff. I get this call out of the blue from the Office of Nutrition Research Director and he said, yeah, I don't know what happened, but I was just told it's not going to happen. It's dead. And I was like, what? What's the reason? I couldn't get a reason. I

don't know. And I knew that the deputy director for intramural research was supposed to meet with Jay Batacharya the next day. I didn't tell her that I got this phone call. I wanted to see how that meeting went. That was a Friday. I emailed her on Monday and said, hey, so how did it go? And this person who had been very optimistic in the past basically wrote to me and said, yeah, Jay wasn't there. I talked with Matt Memley, who was the kind of political interim appointee deputy director. And, yeah, she said, it's not going to happen. And I don't see a path forward. And I wish I could, I'm usually an optimistic person, but that's how I see it.

I was just like, yeah, terrible. Okay, I guess it's not going to happen. And that's where it left. And so, yeah, so not going back to age anytime soon. I mean, I think that symbolizes where the administration currently falls of making a lot of promises, and then when there's an opportunity to do the thing, it's not done. And the things that they are doing are perhaps minutia-related or not beneficial at all or not borne about by evidence. So that's obviously very concerning to me.

For individuals that want to support you, you know, I just had Dr. Jen Gunter on and she said she gave a speech somewhere in Australia, there was a billionaire in the audience who ended up funding an endometriosis research institute for 50 million or something. So maybe we have a billionaire listening. If people want to reach out to support you, where can they reach you? Well, yeah, they can reach me on my website, Kevin Hall, PhD.com. I didn't have one before. I'd have one. But yeah, I mean, I think that that's the question is, can we, if the NIH isn't going to do this, is there another path forward? Can we actually provide, the nutrition science and metabolism community with the kind of support that they need

to actually come up with answers to these questions in a rapid way. Can we actually, we're not talking about billions of dollars. We're talking about, you know, tens of millions of dollars. If you're building it from scratch, if you're renovating, it's, you know, much less than that. And there's stages that we could kind of get to. I think that this kind of research is super important. I think it's been lacking for a long period of time. time. And I think that, you know, I've been talking with some folks about how could we best do this?

How could we best put together the kind of institute that would allow for the, you know, even even industry to have that kind of Chinese wall of sponsorship where they have absolutely no say in the research that gets conducted and the ability to manipulate or influence the research. but they experience in a way that is non-competitive the insights, right? I mean, and how will that inform our policymakers? What's the right science that needs to get done in or to make a difference? Because, you know, I fear that, you know, and I hope I'm wrong, that addressing food dies and discussing ultra-processed foods

in the way that they're being discussed actually does move the needle on public health. my fear is they're not targeting the right things and that they're expending this enormous political capital that the maha movement has really earned right i mean never before in kind of the history of the u.s since maybe the dawn of the 20th century when the fda was created did we have this popular movement of people that were concerned about the food in the american food system yeah and i don't want that squandered i want that used to kind of advance the science and and really give people the answers that they deserve, not just the ones that are easy to do or might sound good. I'm not optimistic about our current administration, but I am optimistic for you to get the

dream lab. I'm going to work on my part to try and do whatever we can to help amplify your message. Obviously, I want to thank you for your work that you've done historically and continue to do in fighting for this because I think it's leaders like yourself that ultimately will get us the answers that I need as a primary care physician to help my patients that my loved ones need in order to help guide their health decisions. So I thank you for that. I think the audience really thanks you for that. Definitely going to be linking your website in the description of this conversation. I definitely learned a lot. So I most definitely want to thank you for all of it. Thanks so much. Thank you. Huge thanks to Kevin Hall for all the work that he's doing. Definitely

check out his book, Food Intelligence. If you enjoyed our conversation, don't hesitate to give it five stars, leave a comment to start the conversation. It really helps us find new viewers for this podcast. And if you want another really good conversation, just to show you the opposite end of the nutrition spectrum, check out my interview with Dr. Jason Fung. Find it. I know you'll enjoy seeing the differences. And as always, stay happy and healthy.