Today's guest on the proof is Dr. Kevin Hall, one of the most influential nutrition scientists of the last decade. Kevin is the man behind the landmark metabolic ward study that proved that ultra-process foods drive us to overeat. 500 extra calories a day without people even realizing it. He spent over two decades at the NIH. He ran the famous to biggest loser metabolism research study. He tested the carbohydrate insulin model in controlled settings and then last year walked away from his dream job, citing censorship of his findings. In this episode we go deep. Kevin's take on the new dietary guidelines and whether the current administration's approached food and health is grounded in science. Why he thinks we're far from done studying ultra-process foods. The mechanism's driving over consumption of these foods. Why your body fights so hard to regain lost weight. GLP want drugs and food industry politics. Let's get into it. Please enjoy. I wanted to start today's conversation with the brand new dietary guidelines for Americans. Okay. A little different to some of the episodes that you've done. They're obviously very topical right now. They just came out in the last month from your perspective grounded in, I guess, decades at the NIH and the broader nutrition science literature that you're across. What were your first impressions when you sold the new guidelines? So first of all, I should caveat this all with, you know, I'm a physiologist/physicist/ you know dabbling in nutrition and try to do my best to understand how the human body works and I'm not in the business of giving people lots of advice and very specific advice on dietary guidelines. So I just want to preface it with that. My background isn't necessarily well suited to kind of provide people with dietary advice. But the guidelines themselves, you know, from what I could tell from the actual documents, right, the things that this kind of new group of scientists who got together to rewrite or reconsider some of the evidence that the dietary guidelines advisory committee and if people aren't kind of familiar with the distinction, right? There's a long history of having a dietary guidelines advisory committee who advises the HHS and USDA secretaries about what the latest science is updating the previous guidelines on a five-year cycle. This time around that dietary guideline advisory committee presented their report and as far as we can tell, it's not clear how much of that report was incorporated directly into the new dietary guidelines. There's a new group of people who were assembled. I don't even remember exactly who all those folks were, but they were given the task of coming up with the new dietary guidelines. And when you look at the overall recommendations, they're not that much different than the previous guidelines as far as I can tell. They still kept the sort of 10% cap on saturated fat, which I think has gotten some people upset. It still recommends that people reduce their intake of refined grains and sugars and carbs and recommends, you know, lots of vegetables and fruit and maybe lean heavily on animal-based sources of protein. And then the pictures that kind of go along with it, the sort of inverted food pyramid, was, you know, maybe it doesn't mesh exactly with the guidelines. I'm sure you could come up with ways to kind of make that make sense, I suppose. But it seemed a little, you know, interesting that, you know, a big slab of beef and butter kind of, it seems like in the top left corner of this inverted food pyramid and how that meshes with some of the actual specifics in the document. I think people have been, you know, bickering about online and other places. As someone who has been interested in how food affects calorie intake and energy balance and the way that that relates to obesity, which then drives up the risk of a lot of chronic disease that people are suffering from, was there anything? And I appreciate that you're not in the business of giving specific nutrition advice, but was there anything in there related to proper processed foods or ultra-process foods that wasn't in there that you would have liked to have seen or was it, was for guidelines, was it pretty comprehensive? I was actually pleasantly surprised that they tried to tackle the issue of highly processed foods. They didn't use the terminology ultra-process foods. They used the term highly processed foods, if I remember correctly. And because I think that the previous dietary guidelines advisory committee tried to do a systematic review of the evidence upon which to answer the question of whether or not diets high in ultra-process foods give rise to increased risk of overweight nobicity. And they came back with a relatively limited recommendation on that basis. They said the evidence so far is limited. And, you know, I was interested in that because they, the way that they decided what their criteria it was for studies that would be included, were set in such a way that, you know, the very sort of short-term mechanistic studies that we'd been doing at the NIH would be excluded because they were less than 12 weeks long, for example. And it's one thing to do that when you have a wealth of data, right? And you've got like tons of data. It's a search from, but why have that exclusion when you're just trying to synthesize the available evidence on a topic that was new to the dietary guidelines for advisory for the advisory committee. And yeah, so I was a little disappointed about that decision early on for that. So I was actually pleasantly surprised that this new dietary guidelines started to tackle this question. And, you know, I thought that they made some reasonable recommendations. But at the same time, I think that there's a lot of nuance in the idea of ultra-process food. And I think we might get into that in this discussion. And so the degree to which people now talk about eating real food and, you know, we have Mike Tyson making commercials for HHS about eating real food and what that means in terms of what does that mean? Like what is what's the definition of real food now? I guess another question, right? From the outside, it seems like there's almost a few different perspectives here. There's the scientific committee that had the very strict kind of God rails, which led to this kind of limited body of evidence looking at ultra-process foods and how they affect obesity. And then there's the other end of the spectrum. I've heard people who have the view of look, you know, we know ultra-process foods are a problem. We don't even need to study them. We should just do whatever we can to eradicate them from the food supply. And what I'm hearing and I'm throwing this back to you. And this is from everything that you've said so far, but also listening to one of the shows and reading your book. What I'm hearing from you is that we can have guidelines that help people understand which types of processed foods they should eat less of. What foods they should eat more of. But we shouldn't just stop studying ultra-process foods because there's a lot more to learn. There's a lot more to learn. And, you know, as a planet, we may have to rely on ultra-process foods to feed a warming planet that has a sustained, you know, wants to sustain a population of, you know, 10 billion people at some point. I think that eliminating the idea that we could have ultra-process foods as part of that solution is, you know, maybe not necessarily the best idea to kind of remove that from the table of conversation, especially if we don't know what it is about diets that are high and ultra-process foods that lead to these associations with poor health outcomes. How much overlap is there based on the more nutrient considerations that we've talked about that those foods tend to be higher in, you know, sugar and saturated fat and salt and low in fiber and relatively low in protein. So I think there's a lot of nuance there that we need to kind of dig through. And yeah, it's, it's I think premature to say let's take this entire category of foods which now represent, you know, somewhere between 50 and 60 percent of the food supply in Western nations and say, yep, we're not going to have any more of those. That's maybe a little bit premature to make that sort of decision. So there's a world where ultra-process foods still make up the majority of the average Americans diet, but it's not having the same effect on their health as the current ultra-process foods that most people are consuming. I think that's certainly possible, right? And I think that the issue is that what we have now is we have a lot of these ultra-process foods do have poor nutritional profiles, right? And they do lead to, I would argue, for a variety of reasons, increased calorie intake, weight gain, and probably have played a pretty important role in the rise in obesity prevalence in downstream chronic diet related diseases. My argument is we need to figure out what it is about those foods because it's such a huge fraction of our food supply. And if we could better understand the mechanisms by which diets high in ultra-process foods have those deleterious consequences and come up with ways to make, you know, gosh forbid, a healthy ultra-process foods if that's even a possible thing. And I don't think it's an oxymoron by definition. It's something that we could actually study and better understand if that's possible that there could be a role. I'm not saying that we wouldn't still want to emphasize eating lots of whole foods and minimizing the kinds of ultra-process foods that we now have, you know, reasonable evidence to believe are deleterious to health, you know, things like sugar, sweet, and beverages, and various types of processed meat products. There seems to be reasonably good evidence that those types of products are not likely beneficial.
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I think that we don't have a universally agreed upon definition of what a Mediterranean diet is. We don't have any problems recommending what a Mediterranean diet is. We don't have universal agreement on what people think is a fruit or a vegetable. A lot of people put tomatoes in the vegetable category and confuse botany with culinary definitions of these things. I guess the question about a definition is, has it been useful? Has it moved the field forward? What was its intent? Was it intended to be used for research purposes or for regulatory purposes? Those are very different things. It's one thing to have uncertainty around the edges and have these edge cases about whether or not given product is ultra-processed or not when it comes to a research program. Then you can do some sensitivity analysis. If we include those kinds of things, what kind of answer do we get when we remove them from the analysis? That's not an option a policymaker has. Policymaker needs to make a definition about if you're going to put into a policy that you need to reduce the number of ultra-process foods in a school lunch program. For example, you have to have a very clean definition about what an ultra-processed food is. You can see various people coming up with lots of different ways to tackle this. Some people are relying on a more nutrient-based idea and have basically targeted the usual suspects, saturated fat, sugar, sodium, and those kinds of things, and have basically used what I think many would argue as an even more solid foundation of nutritional evidence to make recommendations based on those kinds of nutrient-based targets. What is it that distinguishes an ultra-processed food from a process food? This is another question that depends on which definition you're using. Most folks in academia who have done research on ultra-process foods have used the NOVA classification system that Carlos Montero's team has come up with. The very brief classification there is four categories of foods. There's whole foods or minimally processed foods that are basically the kinds of foods that you'd see almost directly separated from nature where you can actually then still wash them. That's a form of processing, I suppose. You can chop them up. You can freeze them. You might even be able to can them if you don't use any sort of additives or preservatives. Those would still be considered minimally processed foods. He's got category two of the NOVA system, which basically are process culinary ingredients. The way I like to think about this category is these are the things that you don't generally consume on their own. It would be olive oil or vegetable oil or salt or sugar, flour, things that basically you are using to combine with category one foods to prepare dishes or meals or create a new kind of food, which is basically the definition of category three processed foods. Category one and category two foods. That's the definition of processed foods. In that category, you'll get bread and cheese and pasta, maybe again combinations of category one and category two foods to prepare these category three foods. Then basically you could almost use this by exclusion. Everything else is ultra processed. There's a long definition that is intended to guide people to better understand what these ultra processed foods are. I think that people quibble about this definition over and over again about because it does contain some things that certainly when I first learned about the definition, I found problematic. Things like the purpose of processing. There's something about the purpose of are you adding ingredients to make it more cosmetically pleasing? Is it industrially produced versus in a home kitchen? These kinds of aspects are a little bit squishier, a little bit more difficult to get your hands around, which is I think a valid reason why policy makers are saying maybe the Nova categorization system might be fine for research purposes. When it comes to making policies and identifying individual foods and whether or not they belong to this category or not, we need a more stringent definition, a more operational definition that can be applied at the individual food level. Some people may just say it's obvious that these foods are not as healthy as real, minimally processed foods. You can just look at them, look at the packaging and it's clear. How do we actually know that when you look at population studies and I think you said earlier about 50% of the average Americans calories are coming from this category of ultra processed foods or maybe even more depending on age, how do we know that it's the foods themselves that are increasing risk of acutymidabolic disease or some other outcome and it's not the fact that they're cheap and the people that are consuming them are often of low socioeconomic status and other variables that could be applied. I think that that's where you get into the limitations of different kinds of studies, right? So in these observational cohort studies, for example, you can start to make statistical adjustments for some of these things and try to see if the effect goes away or gets stronger as a result of making those statistical adjustments. But at the end of the day, there are certain confounds that you can't get around, right? I mean, these are not experiments, right? You can analyze the data in different ways to try to get around it, but it's an important factor. I've argued that we need those kinds of studies as well as the sort of more controlled studies where we take certain factors out of the equation. So for example, you asked the question about, you know, these foods tend to be less expensive and certainly a factor. They tend to also be more convenient. They tend to also be a lot easier to prepare and you don't need as much equipment or skill to prepare them, right? All of those factors are important. And so when I first started getting into this topic, I was interested in, well, what if you remove all those things and what if you just provide people with the foods themselves? Is there something about the foods themselves and you create meals that are highly, you know, have a lot of calories from ultra-process foods versus a lot of calories from minimally processed foods and no ultra-process foods, but matching for the nutrients in the meals that you're giving people? Is there something over and above those other factors that we mentioned that are important, you know, the price, the convenience and those kinds of things? Do people behave differently with these ultra-process meals? And that was the first study that we decided to do in this topic. It ended up being the first randomized control trial on this question. And what we found was that despite presenting people with the same number of calories, the meals were matched for a variety of nutrients of concern and giving them very simple instructions just eat as much or as little as you'd like, you shouldn't be trying to change your weight. And in fact, they didn't know the primary outcome of the study was we were giving them twice the number of calories that they would need to maintain their weight and what they didn't know as we were measuring their leftovers. And the same people were exposed to the highly ultra-process food environment. They were eating about 500 calories per day more on average than when the same people were exposed to the minimally processed food environment and gaining weight in the ultra-process food environment and losing it in the minimally processed food environment. So that says that when at least in that one study, and you know, there's very few of these kinds of randomized trials now, that the food environment that people were in was composed of ultra-process foods, 80% of the calories, they spontaneously chose to overeat calories and gain weight without knowing that they were doing so or intending to do so. And the same people were losing weight in the other case. And that's taking away. They didn't have to prepare the foods by the foods. They didn't have to have any skill and they rated them equally pleasant, which was also interesting, right? So it tells us something even beyond this, which I think is important, which is that the food environment that we find ourselves in is somehow integrating with our innate biology to shift where we're regulating our body weight and shift our appetite in very profound ways, which might give us some insights about, you know, why is it that we've had this increased nobicity prevalence over the past many decades? Is it something about the food environment and what is it about the food environment? And I think that just saying it's ultra-process food in general is a bit of a cop out. I think we want to know what the mechanisms are. What is it about ultra-process foods? Over and above the cheapness and the convenience and the fact that they're heavily marketed and all that sort of stuff. Our studies are suggesting there's something about the foods themselves that are causing people to overeat calories. And just to kind of underscore a point that you made there.
Those diets were matched for macronutrients, so carbs and fat and protein. So what was different? - We were a little off in the proteins. Let's talk about protein and then talk to us about what else was different, I guess, in terms of the characteristics. - Absolutely, sure. So one of the things that was pointed out afterwards is that the ultra-process diet was a little bit lower in the amount of protein that we gave them. I think it was within a couple of percentage points difference. So practically matched for protein, but when you talk to folks like Steven Simpson and David Robinheimer, who are big proponents of this protein leverage hypothesis, which I think is a fascinating idea, they were making claims that, oh, maybe you could explain the entirety of the effect based on the fact that we gave them a slightly lower protein content in the ultra-processed food environment context. I don't think that that's true. We did some analysis after the fact, and I can tell you about a new study that we ran where we actually matched the protein a lot better and we see similar effects. So I don't think that that's the main reason that that happened, but it's important to point out that was a limitation of the study. We didn't quite match for protein. Even though we say like we matched for sugar content of the diets, which is true. But of course, there's a lot more added sugar in the ultra-processed environment, and no added sugar in the or free sugars in the minimally processed diet condition, right? The sugars were contained in fruits and those kinds of whole foods where it also comes along with a lot of fiber. And even though we matched for fiber in the two conditions, the whole food condition had a lot of insoluble fiber, and what we were doing in the ultra-processed diet condition was adding a fiber supplement, which is a lot of soluble fiber. So even though it's one of those things in nutrition, you name something, but it actually has a lot more subcategories that might make a big difference. And I think that's an important caveat when it comes to doing these kinds of nutritional studies. And what was some of the other main differences between the foods, or when you went away and kind of reflected back on the fact that participants were eating about 500 more calories per day on the ultra-processed diet, despite doing your best to match those nutrients, what were some of the other things that maybe kind of suggest why people were eating more calories? Yeah, so maybe I'll take a step back and say, you know, there's lots of different ways you can design these kinds of trials, and the way that we ended up doing that trial was not the way that I wanted to do it initially. Like I wanted to do it in such a way that we would take a ultra-processed product, and then we would have our chefs prepare a minimally processed version of that same product. So we would have a food-by-food comparison, right? The minimally processed version with the ultra-processed version, trying to match for the macronutrients on a food-by-food basis. When I proposed that idea, basically the kitchen staff revolted. Like there's no way we can do this. This is like, we would have to, you know, increase our staff by a factor of 10 or something like that, and it's just not a doable process. And so we actually iterated back and forth on, okay, well, if we can't do it that way, what if we took process version of the food in, an ultra-processed version and did it that way? So same food still. And then the issue was, well, not all of those versions are in our branded food database. And so we would have to then chemically analyze the ones that weren't in the food database so that we would be sure that we matched the nutrients. And that chemical analysis of food is not cheap, right? So then that becomes unreasonable scale of expense that we couldn't afford. So we ended up settling on this idea of, okay, well, look, we're gonna choose very different foods in these different diets, right? So there is no equivalent of a chicken nugget on the minimally processed diet, right? That's clearly belongs in the ultra-process diet. There's like a grilled chicken, obviously, in the minimally processed version, but there's no like chicken nugget equivalent in the minimally processed diet. And so there's very different foods in these two sets of meals. And so we created these seven-day rotating menus that on average over the course of the day were matched at this very high level for the amount of fat, carbs, sugar, sodium, fiber, and then also the overall energy density of the meals that we gave people, the number of calories per gram of stuff that we presented to them were matched. Now later on, people started to say, well, wait a second, yeah, you matched for overall energy density, but in the one case, you've got all these beverages that you're dissolving this fiber supplements, and that's the ultra-process diet condition. But if I look on the plates, right, I'm not in the beverage glasses on the plates, those foods on the plates are higher in energy density. And the only reason you match the overall energy densities, 'cause you're adding these high fiber lemonade in the ultra-process diet condition. And there's this idea that energy density of beverages doesn't really contribute much to satiation. And so we should really look at the non-beverge energy density of the meals. And then, yeah, it turned out that the ultra-process diet had almost double the non-beverge energy density as compared to the minimally processed diet. And people have been studying this for years. Barbara Roles' group probably most famously for studying how energy density contributes to calorie intake in a very powerful way. And then we had this other interesting discussion. So I already told you about the protein discussion, right? So that was another factor that we were potentially playing a major role. Kieran Ford was a co-author on that first paper and he's very well known for his work on texture of food in oro-sensory processing. And the fact that ultra-process foods tend to be softer, easier to chew and swallow, and you tend to eat them more quickly. And indeed, people were eating the meals in the ultra-process diet condition on a gram per minute basis more quickly than the minimally processed diet condition. So that was another factor that could play a role, especially in combination with energy density of the foods on the plate. And then finally, Tarifazino from University of Kansas. So I think it's been on your program. She has, yes. Yeah, so she said to me, "I know you match the overall diets for salt and sugar and fat and carbs, but what about the number of individual foods on the plate that cross these pairs of thresholds that she is defined as being hyper-palatable combinations?" So even though the overall meals were matched for these nutrients, what about the individual foods? Did you present people with more individual foods that were either high in both fat and sugar, fat and salt or carbs and salt? And it turned out that, yep, we certainly did. We would present people with more of these pairs of combinations. And since then, we've worked with folks like Jeffrey Brunstrom in the UK who've looked at the ratio of carbs and fat in the individual foods that we were preparing and how that might play a role, as well as the micronutrient properties of the overall diet. So there's a variety of differences between these two things and lots of theories about what the main contributor was behind why people chose to over-consume calories on ultra-process diets. Okay, let me throw a few things back to you because there was a lot of in there, a lot of good stuff. So just to tie this back to the beginning of the conversation, the reason this is important is that if we can understand what are the actual traits or characteristics that are driving and what I found really interesting and I want to double click on this in a moment, driving it kind of subconscious wanting for, or urge for, for more calories, despite equal pleasantness. If we can work out what that is, then we can perhaps provide advice to the food industry or regulation or whatever it is, incentives to create this category of food in a way where people do not have that same urge to consume extra calories. Yeah, that's right. I mean, if we understood mechanisms by which ultra-process foods in general are thought to be causing harm and that's still an open question is that there's cause or relationship there. And we think that at least down the pathway of excess calorie intake that seems like there probably is a causal path. We've understood that piece. Then we could give both the food industry, consumers and regulators and policymakers the information that they would need to say, how do we minimize consumption of the problematic foods? What are your top three, top two or three things that you would say today, even though we don't fully understand it, that you would say probably explain the extra calorie consumption. Basically, what we did was we went back to that first paper and said, okay, look, now we know there's all these things that are not matched, right? Let's do a post-hoc analysis of the meal to the meal by meal energy intake. And like I said, we were matching over the course of the day. So the individual meals are varying quite a bit in terms of, for example, protein content or the energy density. And so we can ask the question, let's, on a post-hoc way, ask the question, how much of the individual meal, we gave these same people hundreds of meals, did the amount of protein that we presented people matter, if we gave them more protein or less protein, did they eat more calories of that meal? How about the number of hyper-palatable foods, these individual foods that cross these pairs of thresholds? What about the overall non-beverage energy that's in the meal? Or how quickly they were eating the meals? Like we didn't have measurements of the texture, but we did have measurements of the actual eating rates of the individual meals. And let's just put that into kind of a statistical model and let's let it tell us what the most important drivers are and what the direction of the effects were.
And that's not going to solve the problem, but it'll at least put us on a track to then run a prospective study to test our understanding, right? And so we worked on that kind of analysis. We actually collaborated with Terafazino to kind of get her definition of hyperpalible foods and work that out. And we actually applied it not just in that study, but both of this sort of ad-libitum feeding studies that we'd done up until that point. And what we found was that at the top of the list, the thing that had the most, the largest effect size was the non-bivered energy density of the meal. So independent of the different, whether it was ultra-processed or minimally processed meals, if it was low-carb or low-fat, the energy density of the meal seemed to be driving most of the effects. Next on the list were these hyperpalible combinations of nutrients. And now there's some overlap there, right? So there's some foods that are both hyperpalible and energy dense, and then there's some that aren't. And so we tried to disentangle that. And there was actually an interesting interaction effect between those two. The other thing that we looked at was eating, right? And eating, right, did have an effect faster than people ate the meals, the more calories they tended to consume with that meal. And then maybe the biggest surprise was the protein effect, because we fully anticipated based on, you know, lots of other data that a higher protein meal would lead to less calorie intake. In fact, we found the exact opposite direction. The more protein we presented to people in a given meal, the more calories they ended up eating, which was surprising, and I think still a little confusing. But that's the way that the numbers came out. So based on that rank order, what we decided to do was to design a new trial where we tried to vary the energy density and the number of hyperpalible foods that we presented to people while still keeping 80% of the calories from ultra-process foods. So we had, remember the idea was that one of the potential explanations was now that the ultra-process meals that we presented to people in that first study tended to be higher in non-veverage energy density. We tended to present people with more of those calories coming from hyperpalible foods, and they also tended to eat them more quickly, and they tended to be lower in protein. But then we had to choose, we can't do like 40 arms of a study, so we had to choose, okay, well, the top two were energy density and hyperpalible foods. So let's now re-engineer our ultra-process diets so that we have one that's kind of similar to the first one, high in energy density and high in hyperpalible foods. Then we'll do one where we keep the energy density high, but lower the amount of hyperpalible foods. So it's similar to a minimally processed diet. And then we'll do third ultra-process diet where we lower both energy density and hyperpalible foods, but still have 80% of calories from ultra-process foods. And the idea is if by re-engineering these meals in this way, if we're really getting at the mechanism, then this prospective study should show big differences in the number of calories people choose to eat. And. And. So. It's not published yet, but I have presented the results at conferences so I can talk to you about it. The answer is that is that when we lowered both the energy density and the number of hyperpalible foods to match the minimally processed diet conditions. So now you have the same people. There's again, spending a month with us 24 hours a day, seven days a week. They can't leave. We can take complete control over their food environment. I didn't mention that before, but I think it's important. And they're exposed to the minimally processed diet they were eating about 2400 calories per day. And they're losing a little bit of weight. They don't know that they're losing weight. They're back to the scale. They're wearing loose-fitting scrubs and stuff like that. When we gave them the ultra-process diet and just to make things easier for our chefs, instead of on an individual basis, giving people double their individual number of calories. In this case, we decided to give everybody 7,000 calories a day independent of how big or small they were. With that huge amount of calories available in an ultra-process diet condition, they ended up consuming 950 calories per day more than when the same people were exposed to the same number of calories of the minimally processed diet when it was high in energy density and high in hyperpalible foods. And then their gaining weight had a very rapid pace and gaining body fat. So again, the food environment is having a huge effect. Again, these same people are being told, eat as much as little as you want through reporting the same level of hunger, fullness, satisfaction, eating capacity on these different diets. But for whatever reason, that food environment is interacting with our brain in some way as to reset how many calories we want to be eating, at least on this one week basis. When we cut the number of hyperpalible foods, but kept the 80% of calories from ultra-processed and kept the energy density high, the calorie intake dropped significantly. But modestly, by about 160 calories per day. So these people are still overeating calories and they're still gaining weight and still gaining body fat. But when we cut both energy density and hyperpalible foods, it dropped by a substantial amount, I think 660 further calorie per day reduction. Now not statistically significantly different from the minimally processed diet despite now eating 80% of calories from ultra-processed foods. As long as they weren't high in energy density and high in hyperpalible foods, they're eating similar numbers of calories. Nominally still about 130 calories a day higher, but not statistically significant. And now they're losing weight. So the same people consuming an 80% ultra-processed diet and minimally processed diet are losing similar amounts of weight and eating similar numbers of calories. As we've addressed what we think are two of the primary mechanisms by which ultra-processed foods give rise to excess calorie intake because they tend to be higher in energy density and they tend to have these pairs of combinations of nutrients that are deemed hyperpalible. Although I've argued with Tara about this, it doesn't necessarily mean that that's the mechanism, right? It doesn't mean that they think that they're tastier. 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[email protected]" for a special discount on your first order of Iamate daily ultimate essentials. That's IamateHealth.com and use the promo code "Simon". Replace your cabinet full of supplement bottles today. Okay, so again, a lot for us to unpack here. If we just double-click for a moment on the fact that they're reporting similar levels of satisfaction yet consuming, I think you said in the first scenario where it was energy dance and hyperpallible, almost 950 calories more per day, which is a lot. What's the best explanation for what's happening in terms of satiety, signaling, brain physiology? Is our brain sensing that something's missing in these foods still? It seems to me that if there is this increased urge or want for food, there's some type of nutrient sensing that's occurring. So that's one of the theories that I think Mark Schatzger and Jeff Brunstrom are proposing. And I think it's an interesting theory. I'm not going to discount it. I just don't think we know the answer. I think that there's lots of things going on, right? There's the simplest explanations are that when you have very minimally energy
diet, you have to eat a lot more mass of food to get the same number of calories. And that mass tends to go along with volume. And so your stomach has to kind of expand to a certain amount, just to accommodate that amount of food. And that's simple stretch through the vagus nerve and other factors might just signal to the brain something about how much food you're consuming. And when you get to ultra-process foods, which again are the meals are matched for the fat and the carbs and now they're very well matched for the protein content. It's not that they're eating a higher fat foods. It's that they're concentrated in terms of not having a lot of water in them anymore. So the act of making ultra-process foods tends to extract the water from the foods because you're deconstructing the foods from their original food matrix and recombining them and reformulating them in these ways that have benefits from terms of shelf life, right? Because drying food is a way to preserve them and kind of increase shelf life and avoid a microbiological toxicities that can come from spoiled food. But in the process, you're concentrating the food and concentrating the calories. And so that's the reason why they're energy dense. And that might have just this very simple mechanism of the stomach not feeling that same sort of stretch. But we don't know. These are all just mechanistic stories at this point and tell you then go and take that next step further, which is, okay, well, what do you how would you do that? Maybe you like to study where you have like the gastric balloon, right? Everybody has that. And in one case, you give them the energy dense meal, but you fill up the balloon. And the other case, you give them the energy, the energy dilute meal and don't fill up the balloon. So you have the same stomach stretch to do. They still have differences in the number of calories that they that'd be a really fun study to do. I don't have a lab to do it. That's another story. Yeah, we can we can save time for that story later. But I think that's the point is that we can come up with all sorts of mechanistic ideas and many of them might be testable experimentally. And I know it's very unsatisfying to people because they like to hear mechanistic story very quickly after a result like this. But I think that that can sometimes lead us astray as well. And now that I reflect a little bit more on what you just shared about that study, the fact that you had those other arms where you changed the energy density and then the energy density and hyperpallotability according to to Terafosinos definition anyway. The fact that that tweaking those led to such significant decrease in calories and it was no longer significantly increased compared to the minimally processed diet. That's super interesting in and of itself. And I wonder based on those on on that arm of the study where you reduce energy density, decrease hyperpallotability, are those changes that you had your chefs and your team make? Are they realistic changes that the food industry could make? I had proposed actually a separate government program to actually start to do that original study that I talked about before, which was the food by food and work with food technologists and the food industry to start to make these minute reengineer individual foods along pathways like energy density and hyperpallotable combinations to see if we could reengineer some of these ultra processed foods to kind of mitigate their negative consequences. It was a very humbling experience I was spent about nine months trying to get members of the food industry interested in in collaborating on on a project of many webinars and basically the collaboration was not asking for money. We were saying we would the government would provide them with money to participate and have folks kind of participate in these programs. And I spoke to more than a dozen companies. Some very big that you will have all heard of but I'm never going to name names because I did this under an inemity. Some that you've probably never heard of before in your life. And of them more than dozen we got to the stage where we basically said you know this for this program to go and release this money from this government agency we at least need people to say that their in principle going to apply for this money and come up with come together with academia and develop project teams that would basically implement these kinds of studies and and industry involvement was key to do this. And I was just very disappointed that only three of the more than dozen companies said that they would be willing to even say that they might apply for the money. Everybody else was like yeah no I don't think that we really have a problem. It's not a big deal. Now this was years ago right this is not the current environment. It's not the when it's you know ultra-process foods were you know a topic of conversation among public health folks but it wasn't really reaching the same level of consumer interest as it has in recent years. So maybe things would be different but the point is I think that you could use this kind of information to reengineer into individual foods. Now clearly we didn't have that in this study. So what did we do right? Well it has to do with we're making these interventions not at the level of individual foods but at the level of the meals. And so what's the way that you can not change the number of calories from ultra-process foods very much but change the energy density of a meal. Well you can add a lot of fruits and vegetables right? So instead of having your chicken nuggets on their own you can make them as part of a salad. Chop them up put them on a salad and now you haven't added many calories but you've changed the overall nature of the of the meal instead of pairing it with french fries which are energy dense you've paired your chicken nuggets with a salad and this could also give you some practical advice on how you can still incorporate ultra-process foods into a meal in a way that possibly will mitigate the overeating aspect of these foods. And if someone's thinking oh that's cheating you added on processed foods so back to did you say that the study design it was 80% ultra-processed 20% of calories of calories from ultra-processed right? So not the mass foods right 80% of calories are coming from ultra-processed food. And then again this is one of the challenges of nutritional research right is that you have to come up with ways to manipulate these things and if you're not doing it at this highly technical level on a food by food basis you have to come up with other ways to do this right so you know you're either making soups and you're diluting the thickness of the soup in some way that can change the energy density of a soup for example or in this case where what are we combining these ultra-processed foods with to make a meal and how can we vary that so I know that when people look at you know one of the things that we'd like to do in our in our studies is that we provide photographs of all the meals right so some people will you know kind of block it the idea it's like well wait a second you've got all these minimally processed foods in the highly ultra-processed diet conditions yeah but they still don't make up very much of the calories and it's still most of the calories are coming from the ultra-process foods. Yeah you mentioned Bob or Rolls before and she wrote a great book volumetrics for people that haven't haven't seen it but this gets me thinking about her chef and talks about like a soup strategy having like a water-based soup with with a meal to lower calorie intake. Yeah no I think that there's lots of strategies that people can potentially come up with and I think that the criticisms of all of these kinds of studies are that you know you you can maybe do that for a meal or two meals and are you kind of eliminating some of the advantages of the ultra-processed diets because now you're pairing them with things that you actually have to prepare right on our studies it's not a big deal because people don't have to prepare them right but on a practical basis you're taking something with that was basically ready to eat ready to heat and you're adding a few more steps because you've got to you know cut up the vegetables and you know make up whatever whatever you're pairing it with to kind of lower the energy density and and maybe increase its beneficial nutrients in the foods and the meals I should say so I think that these are fascinating questions and how how much can people actually do that on a long-term basis especially if we're asking people to kind of you know is increasing the price is it increasing the prep time is it increasing the amount of skill and equipment that they need to have to prepare these meals great questions we didn't factor that in we're just interested in the properties of the meals themselves. To your point about engaging the the big food companies in this topic particularly this idea of reformulation if I was an owner of a big multinational company that was selling these foods I'm not sure if profits were my main priority I'm not sure how engaged I would be either with science that's looking at helping people reduce their want for my foods and consuming less calories. Yeah I guess the question is not whether or not you're changing the want for the foods because they're happy to I mean they're happy to sell you diet coke as much as they are coke right and coke has no calories and coke has lots of calories right and what they're interested in is the profit right and I think the question is is the re-engineering and reformulation of those foods going to make them inherently more expensive and more difficult to sell to people is it going to have other downsides like people like you're you're intending to say which is they're just not going to like them as much well you know that might be the case but at least in our hands again people do not report liking the meals that led them to consume many fewer calories any less than the meals that led them to over consume calories. Let me rephrase it.
that if people may like them the same, but if they're eating 500 or 900 calories less per day and then you multiply that out across the population, that's impacting the total net volume of food. And in this case, ultra-process food that's consumed. - Yeah, so another factor that I think is probably interesting for folks to consider is how much of the food that we currently produce that gets wasted already, right? So, and we did a study back in 2009 to try to quantify, we saw the increase rates of obesity and we were trying to track the calories. How much of the increase in obesity could be explained by the number of calories in the food system? And as we know over that time period, yes, the amount of ultra-process foods has gone up as well. - And I think the interesting point there was that it's not like we're demanding those calories. It's not like there's a poll on the calories that the consumer is saying, we need more calories and we need more of this kind of food. It's a push in the sense that of the increase in the calories available in the food supply corrected for exports and animal agriculture and all these types of things, the calories that were actually available in the food supply for people to eat on a per capita basis. It went up something like 800 or more calories per day since the 1970s. To explain the rate of increase in obesity, you only need to have consumed about a third of that. So two thirds of the increase in available calories ended up in the trash. And in fact, we independently got data from the Environmental Protection Agency that tracks food waste in municipal landfills and per capita, food waste has gone up in the US by about 50% since the 1970s. That's how much we calculated it has gone up on a calorie basis as well per capita. So we've really been taking a food system with a lot of calories. In fact, if you just look at the major commodity crops that for food, right, the soy, corn, wheat, and rice in the US, we produce 15,000 calories per person per day. Wrap your head around the back. Now a huge chunk of that goes to produce biofuels. So we take basically some corn and soy and convert that to ethanol and biodiesel. So we kind of offload some of those calories 'cause we have so much produced. We take another huge chunk and we feed it to animals to basically grow animals. And of course that metabolism is inherently a process that produces heat and not every calorie of food that you eat thankfully gets deposited on the body. And so an animal therefore you have to feed a lot of corn and soy to make it grow calorie of meat as a result. And so at the end of the day, once you've got that, that's when you get your available food after accounting for exports and imports. And that's when even still you're wasting a huge amount of food. So we're finding incredibly clever ways to engineer this glut of calories that our food system produces, offloading some of it to biofuels and offloading a bunch to animal agriculture and then creating really clever ways of making high fruit those corn syrup out of a lot of the corn, right? And figuring out really clever ways of re-engineering these foods and marketing them and testing them in the marketplace and almost doing like an evolution in the marketplace of the selection of the fittest, which are the ones that sell the most. So we've really been pushing these calories in some sense and selecting the ones that were the most successful, but still a huge chunker ending up in the trash. So this question about what it is that we want versus what it is that's available to us that's being pushed on us in this way is I think a really fascinating question. - I'm hugely selective about the supplements that I put into my body because the supplement industry is a low trust category where companies don't really have someone watching over their shoulders keeping them accountable. That's exactly why I partnered with Momentus. They weren't satisfied with the industry standard so they built the Momentus standard. Their own commitment to doing things the right way, not the easy way. Every single Momentus product is independently certified by NSF for sport or informed sport, meaning that it's tested for contaminants, for heavy metals and band substances and verified for label accuracy. So you always know exactly what you're putting into your body. That level of testing and transparency is why Momentus has earned my trust in what is a low trust category. Two of the five supplements that I take every single day are made by Momentus, their plant-based protein powder and their creopure, creatine monohydrate. Right now Momentus is offering our listeners here at the proof up to 35% off your first order with the promo code, the proof. Head to livemomentus.com and use code, the proof for up to 35% off your first order. Are those calories that we're wasting? Is that coming at the cost of the food industry or the consumer or is it a mix? Yeah, I mean, it's pretty much, I mean, they're being purchased, right? So I mean, there's a lot of attention on the idea of how much waste at supermarkets or when there became a bunch of people surviving by diving in dumpsters, right? Like there's a huge amount of waste that happens at supermarkets just to kind of keep the produce on the shelf that's beautiful condition and always stocked. And as a result of doing that, you end up having a certain amount of waste built into the system. But the vast amount of waste is occurring at the consumer level. So it's buying the food, putting it in the fridge and or on the shelf and thinking you're gonna get around to eating it and never actually getting around to eating it or it's spoiled or it's a little stale and not to your palate anymore and it ends up in the trash. So the vast amount is kind of at the consumer end. So how do we push for an environment with as less food waste at the consumer end and less calorie consumption at the consumer and whilst keeping these big food companies which are really important to food security, keeping them happy and profitable at the same time. - Yeah, no, I think these are some of the questions we explore in the later chapters of our book, right? Which is that what we have is a really unique situation, because we've had for centuries, probably since the beginning of agriculture worried about feeding the population, right? That there's Thomas Malfus had this idea that we can't, the population grows faster than our ability to increase agricultural production and he's been spectacularly wrong about that. (laughing) In other words, we've come up with lots of technical ways to increase yields of our crops, to come up with new uses for those crops, to specialize in crops in certain areas, as opposed to others in ways that have outpaced population growth in the way that we just mentioned. So that in the US, we produce 15,000 calories per person per day just in those four major commodity crops. That's just in the US, right? So there's this glut of calories, right? And it has been on purpose, right? I mean, a lot of people have been worried about this Malfusian problem for a very long time in policy and agricultural research has been, can have put in place to maximize production of calories and protein as in this kind of nutrient-centric way that we need calories and protein to feed the population, and we need to have enough of it to feed the population. And with this worry that there's never too much, right? I believe it's produced the obesity epidemic, right? I think that we've offloaded those calories to mostly in the trash, but a third of those excess calories since the 1970s have probably been generating the obesity epidemic. And now we're in a situation where we can actually, Malfus didn't know where we were going to plateau, right? In terms of population, it was always this increasing exponential in his time frame, and that was the problem, right? It was always growing at a faster rate. Now we actually have reasonable statistics and we can say, you know, look to 2050, 2060 or so, the world's population is going to plateau. In fact, it might actually overshoot a little bit and then come back down. We know where the target is. We know how many calories we can produce now. We know how much agricultural or arable land has been made available to humans and how much we can do with it. And we need to kind of start thinking about a broader scheme upon which to maybe look past the obesity epidemic for now. Now that we have lots of different treatments to look at the folks who are most susceptible to these changes in the food environment, that's a really wonderful prospect that we can treat the most susceptible folks and look past that and say, you know, and the next several decades, the problem that we're going to have is how do we still produce enough calories without wasting the amounts that we have? Given our constraints on water resources, fertilizer, producing calories and protein and actual healthful foods in a sustainable way that's going to kind of feed the planet and people in the way that's going to improve the health of all those things. And I think that's where folks like, you know, the Ead Lancet Commission were trying to get at some of that, right? And I think that there's a super valuable exercise.
And you know, I don't know that they got it all right or and neither are some debates about these things But I think that that's the right conversation that we need to be having and thinking about yes There's the individual aspect which is you know, what can I do that's best for me? this kind of smaller scale population aspect of what what do we do to kind of address diet related chronic disease and then in the near term But then we also have to look as a society as a whole about where we need to be in the next several decades to kind of hopefully keep Humanity as a viable At a high level right without you know mass starvation that mouth is warned us about or mass disease as well Get back to the the new dietary guidelines it did It seems like the the US government at least when it comes to the dietary guidelines doesn't want to to to talk about Sustainability in the context of food. Yeah, it's an interesting. It's an interesting point Although I've been encouraged in the past few days hearing a little bit about the investments that HHS and USDA are putting into regenerative agriculture and trying to think about Research in this matter to kind of you know, how do we actually come up with way to grow? crops and healthy crops more sustainably and feed people better It's it's a small piece of the puzzle But I think you're right that kind of the focus at least the messaging on kind of red meat and these kind of animal-based products that are very Intensive from and I don't think anyone Really argues that at a population level to kind of get a yes, there are kind of these niche markets where there's a lot of talk about Sustainable beef production and things like that and yeah, they can it certainly can be but to feed a population of 10 billion people in this way with with the kind of Amounts of meat that people are talking about. I don't think that there's anyone serious that that thinks that that's possible This is not my area, but you know, I'm just reading the best scientists that have been talking about this for for quite some time and sure if you're Living in a small rural community and there's like a regenerative farmer that has a cows and and and pork and whatnot That's raised that way. Yeah, sure. You're gonna pay a premium for it and that's probably not doing any damage to the environment But let's not pretend that that can be scaled to feed the populations at large. Yeah, I mean that Very much echoes. I had a conversation with Dr. Hannah Richie. I'm not sure if you know her from our our world and data and she You know, we don't need to digress on a linger on this point for too long But she she basically painted this picture of one thing that the current system does very well is Extracts a lot of calories from relatively small area of land and when you move to more Sustainable animal agriculture or practices while they can be better and at an individual level it might be the better decision On scale it would to produce the same number of calories from meat today It would just require so much land that it would be devastating to the planet. Can we come back to your Your ultra processed food study for a moment here. I haven't I haven't heard anyone ask you this Was there any meaningful differences between subjects? I know that average was about 500 calories more on the ultra processed diet But did that differ between individuals? Absolutely. Yeah, there was some pretty large amounts of variability and Not surprisingly the the differences in how much people consumed like explained very much of how much of their weight loss or gain that they were Experiencing on these two very different diets. So we had I think it was three folks who basically ate more Less the same number of calories in the ultra processed diet condition compared to the minimally processed diet condition and their weight Changes were more or less similar in both diet conditions and then we had wide range of much higher levels and one I think was eating 1700 calories per day more in the ultra processed diet as compared to the minimally processed diet So a huge amount of variability Again, it's we're talking about 20 people in that study. So it's not a large number of people When we went back and asked questions like was did men respond more to ultra processed Dites than the women the answer was no not statistically significantly differently I mean the men consume more total calories than women in both diet conditions on average But the difference between the diet conditions was not statistically significant But and again, these are extremely small studies that they weren't powered to detect these things These are really just exploratory things But we haven't been able to come up with anything even in this exploratory analysis that can explain that kind of variability And the other thing that's important to mention Is that we don't even know how repeatable that variability is right just because we saw at one time I had a conversation with Marta Catan who is famous for several things But one of the things he did was a remarkable experiment saw unsaturated fat and LDL cholesterol and he sought quite a wide range of variability In the participants in his controlled feeding studies where you know some people responded with a huge increase in LDL cholesterol To an increment and saturated fat. Oh, there is not so much and he told me that he was really interested in that variability and And he brought some of the same folks back for another experiment and it wasn't even repeatable within the same person So the second time around the responder was not a responder. So there's just a lot of noise in biology Unfortunately, I wish I knew of the CGM studies looking at Oh right, right. I was paying a blood glucose Yeah, yeah, no, it's the same sort of story right we attribute a lot of signal to what is oftentimes noise And designing the right studies to kind of disentangle the signal from the noise is I think it's tedious and not necessarily the The most exciting type of studies run, but I think it's really important to try to disentangle that otherwise We kind of run down these false paths to basically you know fitting our models to noise as opposed to signal I guess my question was coming from a big a question which is Do you think some people are more vulnerable to the current food environment because of biology? Yeah, let's step back. I think this is an important conversation. We've known for You know many decades now ever since Mickey Stunker's classic twin studies that obesity for example Has a huge heritable component which presumably means it's a genetic basis and that has been kind of documented over and over again And now we have you know these polygenic risk scores, right? Which still don't explain all of the variants in BMI But you know you put hundreds of genes together and you can start to explain why some people are more likely to have obesity than other people So there is a huge genetic component We're still not able to explain on this kind of gene by gene basis All of the heritability, right? So what do I mean by that? I mean that when you kind of do these kind of classic heritability studies Which I'm not an expert in but where you take twins and then adoptive that have been reared separately and Adopted and then you take fraternal twins and versus identical twins And you do these kinds of studies and look at for example body mass index, which is a very rough sort of measure of body size and adiposity BMI tends to have a heritability of something like 40 to 70% Of the variation within a given environment is due to this heritability turns out You know, there's a lot of hope when we've discovered the leptin gene and this family of people who had a mutation in the leptin gene That made their molecule that's leptin is a molecule secreted by fat cells that tells the brain How much fat we have on our bodies if that doesn't work properly the body thinks it's starving or the brain thinks it's starving all the time And these these folks end up gaining a huge amount of fat very early in life There was a huge amount of excitement when that gene was discovered and the fact that we could actually observe it in people But it turns out that it's exceedingly rare I just like it explains, and maybe one and a million cases of obesity So there aren't these single genes that explain, you know, the heritability It turns out it's probably hundreds of genes contributing a tiny tiny bit to your susceptibility to obesity Now That's a completely separate question about well Obesity prevalence has increased quite dramatically Since the 1970s for example now BMI has been going up for Even longer right if you look at there's these classic studies where you look at conscripts in the Civil War in the US And you can see BMI has been creeping upwards for a very long time and it's it's that that It's been happening because of addressing nutritional deficiencies in the past So height and weight has been going up and BMI has been going up in parallel But weight and height have kind of dissociated in more recent years and average weight has been going up faster than height since the 1970s And when you put a cutoff as to a body mass index the prevalence of obesity has been going up even more because you're at a Particularly a sharp part of the distribution, but weight has been going up a lot Now the question is is that the genetics susceptibility on the background of this environmental shift That's explaining the increased prevalence of obesity I think that that's the case. Understanding how that works is a different question And I don't think we understand it very well at all What we can see is that when you change people's food environments in these kind of silly studies like we do On average people are consuming very very many different numbers of calories and either gaining or losing weight Now I don't know
expect that those effects are going to last forever. They're eventually going to have, I think, body weight is under feedback control. And as you've been overreading for a period of time, your appetite will then go down and you will re-equilibrate at a higher weight. And similarly, in the reverse situation, you will eventually re-equilibrate at a lower weight. And the extent to which genetics determines the parameters of that feedback control system, as I think a really interesting question. And how does that work biologically? I don't think we have really the faintest idea yet, unfortunately. We know a lot about the neural populations that regulate body weight. We actually have very little understanding of how the environment impacts those circuits. There's only been a handful of studies, even, you know, among colleagues of mine, who've done the neuroscience of looking at this, of how these different neural circuits interact with each other and sense the environment in ways that are having an effect on the activity of these neural populations in such a way as to regulate body weight at very different places, given the environment. But we know that phenomena is robust in mice and rats and humans. You expose these animals to very different food environments. They regulate weight at very different places. So this idea that there's a set point body weight. Well, if it's set, it's being set by the environment just as much as the biology and it's that interaction that matters most. I want to go back a little bit to before your ultra-processed food study. If I recall correctly, I mean, the earlier part of your career, you're very well known for conducting these studies that kind of pitted carbohydrates up against fat. And I guess there was all sorts of hypotheses at the time around. Our is a calorie, a calorie, a carbohydrate's uniquely fattening, is fat uniquely fattening. And you ran all these experiments and need the turned out to be a clear driver. Would you say that it's it's case closed today on the idea that carbohydrates or fat are uniquely fattening, uniquely a problem? No, I don't think the case is ever closed really, but I also think that the different studies had different contexts, which I think are important to unpack. Again, I came into this field from a very different place. I was trying to build computer simulation models of how the body adapted to different fuels. And in the diet end, within the body, and where we get our fuels from when we're not eating and how that changes when we are eating and those types of things. And I heard about this kind of phrase of a calories, a calorie. And I didn't really know where it came from at the time. It's like, what do you mean by that? Number one, of course, you just repeated the same word and put in "is" in the middle. It's like, how is this insightful? And the challenge that I was having was, you know, I'm trying to build this computer simulation model where you have this input of nutrients, carbohydrate fat and protein. Your body's built of those nutrients, along with some water and minerals. And how is it that when we change the proportion of the nutrients coming into the body that the thing just doesn't break apart? I mean, I can't just kind of pull up my D's a lot of mobile to a fuel station and put regular gasoline in the fuel tank and expect it to work properly, right? But for whatever reason, we seem to have this remarkable ability to fuel ourselves on a wide array of mixtures of carbohydrate fat and protein. And what's the underlying physiology that allows that to happen? So the idea that the body treated all calories in terms of carbs, fat and protein as equivalent was it's patently false, right? It's just not true, right? I mean, there are internal responses to carbs are very different than they are for fat and they're very different than they are for protein. And when we walk through some of that physiology in our book, but it's classic physiology that goes back to the beginning of the 20th century. But prior to that, I found out where this concept of a calorie's a calorie came from. And it was this really brilliant scientist named Max Rubner from Germany who noticed something very interesting in a kind of a mystery that his mentors had, which was they were doing these experiments in dogs where they would take a dog and they would try to measure how the rate of fat body fat loss of a dog when it was starving. You're not giving it any food at all and you can measure how much fat it's losing. And they asked the question, okay, well, what happens when you feed the dog? Different kinds of nutrients, like what happens if you feed a dog sugar? And lo and behold, you feed a dog different amounts of sugar in the rate of fat loss. Well, change, it'll be slowed down as compared to feeding it nothing at all. And you can do the same thing with fat, right? So large, you can give the dog different amounts of large and you can slow down fat. And the conundrum was that you had to give twice as much sugar as large to slow the body fat loss to the same amount a little bit more than twice as much. And so why? Why is it so much different per gram of sugar than per gram of fat to keep the dogs fat mass from going down at the same rate? And what Rubner did was something really interesting, he took the sugar and took the fat and tried to figure out how many calories, how much heat energy are in these two things. And what he found was that it precisely matched the ratio per gram as the amount of sugar and fat that would prevent the body fat loss to the same extent in the dog. And so he was a one who came up with what he called his isodinamic law that the cow, it wasn't the mass of the sugar and the mass of the fat that mattered for slowing body fat loss. It was the calories of sugar and the calories of fat that mattered when it came to body fat loss. Now he had no idea what was going on inside the body to make that a, seeming equivalency of calories for body fat changes. We learned about insulin only after it was discovered in 1920s in Toronto by banting in best in MacLeod and we started to understand and unpack the remarkable hormonal changes that take place inside the body that shuttle these nutrients from different organs in their storage form. And in such a way, they do it in a remarkable way so that the fuels that are being selected to burn are such that what's left over ends up either as fat inside fat tissue or being removed as fat from inside fat tissue, almost independent of how many, how much of that came from carbs or fat or protein. And that's amazing to me, right? So that was like, okay, now can I model that in a computer? And is it perfect? Like, is this a, did evolution devise this so that it's a perfect system? And what we, what I kind of came to the conclusion was that, you know, you could actually engineer a diet where there could be really tiny differences. And maybe a calorie isn't exactly a calorie. And that led me to the first study that, that we ever did, which was based on a computer simulation model prediction, which was that if I cut the same number of calories from a diet that was weight maintenance sort of diet to keep people's body fat constant, if I cut 30% of calories from carbs versus cutting 30% of calories just from fat, the prediction of the model was that the reduction in fat would lead to just a tiny bit more body fat loss than the same number of calories coming from carbs. And the only way we would be able to measure this is if we put people in these respiratory chambers and measured on a daily basis, how much fat they were burning and how much fat they were taking in. And so that was the first study that we, that we published. And it was happening at a time when there was this resurgence in low carb diets, they were getting to be extremely popular. Gary Talb said, published his book, Good Calories, Bad Calories, and it was, you know, New York Times best seller and everybody was talking about restricting carbs. And so here we came along and we had this computer simulation in this, and this result, which showed actually, you know, what over this really small period of time, all these major hormonal changes are going on inside the body. And the calories almost a calorie, but at least in this particular circumstance, a little bit more body fat was lost in the reduced fat period as compared to the reduced carb period and the same people eating the same number of calories in different occasions. And so yes, that was my first sort of step into this world. I didn't know I was doing a, because it wasn't a weight loss study, right? It's like not, it's a meaninglessly small difference in body fat over a very short period of time. But it got a huge amount of pushback from the low carb community. It was my first introduction to some of the nastiness that kind of occurred when people receive a result that doesn't match their kind of their way of thinking about things. So yeah, so we've done several studies since then that basically I think show that this system isn't perfect that the calorie isn't exactly a calorie when it comes to body fat loss. But the differences are incredibly tiny. And certainly they're tiny even when it comes to how many calories are being burned by the body. So this sort of efficiency, the metabolic efficiency on these different diets. Yeah, you can detect small effects. But they're you know, a hundred calories. Maybe if you believe some people's data, two hundred calories a day differently. But compare that to what happens when you put people in two different food environments that vary in energy density and hyperpellable foods. It's a very small effect size. When you were riding or published that first study, were you aware of the carbohydrate insulin?
model at that point. That's a good question. Yeah, because I'd read Gary Gary's book. I credit him with the, I mean, he was, I think the first one to really put the way that we think about the carbohydrate insulin model together. I think he was really the first one to put that together in the sort of modern way. I mean, people have talked a lot about, you know, lipophilic fat tissue in the past and had, like, those are very historical concepts, but the idea that, you know, carbs in the diet causing excess insulin secretion, causing the fat to be, you know, prevent lipolusus from occurring because, as we know, fat tissue is incredibly sensitive to insulin and that that leads to some sort of internal starvation that leads people to, to kind of decrease their energy expenditure and increase their hunger. That sequence of events, at least from my point of view, the first time I heard that articulated was in Gary's book, which is pretty remarkable for a journalist, right? I mean, he's not a scientist. He's a journalist and that theoretical concept, I thought was really interesting. And in fact, I remember first meeting Gary while that study was ongoing, right? And I remember he gave a talk at the NIH and we met afterwards and I remember walking back to my office and I said, you know, we got this, we got this study going on and I'd love to get your prediction about what would happen, right? So we've got this one case where we've got the same people, we reduce carbs and I'm guessing that their insulin secretion is going to go down, whereas I don't think it's going to go down as much with the reduced fat. According to your theory, what do you think is going to lead to more body fat loss? And he predicted that the reduced carb diet would lead to more body fat loss. I mean, I think that when the paper came out, he wrote a pretty scathing editorial about it in the New York Times about how it's a meaningless result, how it ignored the hunger aspect because we made people eat exactly what we were giving them. Fair. That's right. We didn't design the study to do that point. But yeah, I thought it counted as evidence against this theory, right? You had a case where carbs were definitely lower. Insulin secretional was 20% lower and it didn't go down in the reduced fat case and yet they lost more slightly, not a meaningful amount, but slightly more body fat in the case with the reduced fat diet and they burned more calories in that case as well. And subsequently, since then, if I recall correctly, you have done a study comparing low carb to low fat in the setting where people can eat as much calories as they want. Yeah, that's right. So we did a few other studies about doing a longer durations of more extreme kinds of diets, very ketogenic diets, over like a two month study. And yeah, we saw some very small effects on energy expenditure and fat differences again. In one sense, working towards maybe what the predictions of the carbohydrate insulin model might be, although not nearly to the same magnitude as we had planned at the outset of the study and then the slowing of fat loss was kind of against the model predictions on the ketogenic diet. But then yeah, we were interested in, well, what about the the hunger aspect and the appetite aspect? And this was, we, I just finished the ultra-process food trial and I said, well, look, now we know we can actually measure what people eat and it can have a meaningful effect. Let's design two diets. Basically, the same study design as the ultra-process food study design. And in one case, we'll give people a ketogenic diet and in the other case, we'll give them a very low fat sort of diet. And the only kind of ecologically relevant low fat diet that we could come up with were the category of the vegans who, you know, they skew all of the, they don't even like olive oil, right? All fats and oils are bad and but they actually had cookbooks and that we could base our menus off of. And so we had like the 75% carb, 10% fat diet in that arm. And then we had kind of a pretty traditional sort of keto with a bunch of animal-based products in the other arm, which was 10% carbs and clearly induced ketosis. So yeah, so same sort of study design as the ultra-process food study design. People spent a month with us in two week periods. They consume one diet or the other. And in that case, yeah, we saw that the people when they were on the ketogenic diet, they consume more calories than when the same folks were on the reduced fat diet. Again, energy density being a primary difference between the two, right? So in this case, we're manipulating macronutrients having much more fat in the ketogenic diet. And even though we kind of gave these people a kilogram of non-starchy vegetables a day to eat as a base, that was a common base between the two, the energy density of the ketogenic diet was much higher. So at least that's our main hypothesis as to why those folks ended up eating so many more calories when they were on the ketogenic diet. Was there a bit of pushback from the low-cob community after that paper came out and there's always a pushback where any of the criticisms constructive good feedback. So I want to be clear, all of the criticisms are constructive, right? I mean, the discussion about what the motivation of the study was or that I was rigged or something, that's not constructive. But you know, there is no perfect study, right? And I think it's important. And one of the things I hope people would appreciate is I take all these criticisms. You know, the first study we talked about with their selective restriction, they said, "Oh, it wasn't low carbon, if it wasn't long enough." It's like, "Okay, so we did a two-month study with a ketogenic diet and, you know, we didn't see much of a big effect." And then, "Oh, as well, you know, you're not controlling for the appetite and hunger." And it's like, "Okay, well, let's do a study with appetite and hunger." And so we try to take on and board many of these different criticisms. And in this one, yeah, it's also not a perfect study. And yeah, there are things that could have been done better, not practically, however. Part of the problem is when you're designing studies, you have to wrestle with, pick your poison sort of aspect, right? So in this particular study, I think that the biggest criticism, and it's a valid criticism, is that there was no passive washout between the two diet harms, right? So they went directly from the ketogenic diet to the low fat diet or the reverse, right? And we tried to account for that by pre-specifying a primary outcome, which was only looking at the last week of each of the two-week periods. So that's something called an active washout. I learned that afterwards, but that's what they call it in a drug trial. It's called an active washout because you're basically ignoring the first, you're allowing the first part of the study to act as your washout. And you only look at the second part. And we still saw the effect. And it was slightly lower in magnitude. And we asked the question at the time, did the size of the difference between the two diets? In other words, when every single participant ate more calories on the ketogenic diet compared to the low fat diet. And we asked the question, the magnitude of that difference, did it depend on the order that people were assigned to the diets? In other words, was there a significant difference between people who first went on the low fat diet and then ate more calories on the ketogenic diet or first went on the ketogenic diet than ate less calories on the low fat diet? And it wasn't any different. So that's what we published. And then later, we looked at our data and said, but there's something else interesting going on here. Even though the difference between the two diets wasn't statistically significantly different depending on the diet order, if you happen to be randomized to one diet sequence versus the other diet sequence, we saw very different effects on, for example, body weight and body fat. So if you were assigned to the ketogenic diet first and then to the low fat diet, overall over the entire duration of the study, you ate many fewer calories than if you happened to be assigned to the reverse order. So the difference between the two pairs, like the two two week pairs wasn't any statistically different, but the two groups, the two parallel groups, there was this big effect. And I thought it was really fascinating. We kind of wrote that up and published it. And of course, people then subsequently tried to re-analyze the data in a dozen different ways, some sense. And in one case, they made a complete mess of the analysis and treated every data point as if it was independent and had p-values of like 10 to the minus 12 or something. It was really kind of awful re-analysis. But yeah, they tried to interpret it as being supportive of the low carb diet and the carbohydrate insulin model. And it's like, okay, I didn't quite understand their argument, but it was interesting. And so I think what they were trying to say was that the carryover effect from the low carb period into the low fat period was so important that it trumped any effect of the increased insulin during the low fat period to basically have its effect. In other words, the insulin levels two weeks before on the reduced carb diet were driving the effects on appetite two weeks later, despite now having a much higher insulin level. And so what they were focused on was that second period in saying, oh, it's the carryover effect that's really driving this and it's really the low carb diet that's winning. And then when we pointed out the problems with that analysis, they turned around and said, oh, well, yeah, now forget the second part. We got to throw out that data because it's all garbage because of the carryover effect. It's really the first period that we're interested in now. And now we think we see a hint of a signal for the low carb diet in that period. How many ways do you want to cut the data off? Yeah, exactly. It's like that kind of idea of torturing the data until confesses what you want it to and so, you know, we published all the raw data so people can look at it however they want. But I think that's the reason why you pre-specify the
things, right? You say, here's how I'm going to look at the data because there often is a way to carve up the data to get the way the analysis that you want. It's the so-called researchers degrees of freedom. And I think that's been one of the most positive developments in clinical trial design over the past several decades is that we have to register our studies, pre-register how we're going to analyze them in advance. And you have to report the data that way. That should be your primary analysis. You should say, this is way I plan to do the study here is how it was. Yeah, there's caveats. And maybe I think it's a better way to analyze the data. That should be an exploratory analysis in the same sort of way that we did with our ultra-process food study, right? We've then explored, oh, well, what about, you know, hyperpalible foods or what about these other things? And say, this is a post-hoc exploratory thing. The original results stand, but now we think we have a better way to design a new experiment. And that's that second piece that's almost never done, right? It's like you think you understand it based on some post-hoc explanation, which matches your bias or whatever. And very few people then say, okay, well, now we know how to design a better experiment to really test this. And let's prospectively go ahead and do it. Okay, so I'm going to ask you a question in a way that may prompt you to give some personal advice. We'll see. I know that's not your thing, but I'll do my best here. So let's say, okay, you've done your computer model study, and then you've done these metabolic board studies. And you're in the elevator. Someone recognizes you. They're trying to lose weight. And they say, "Doc, do I try a low fat or a low carb diet? How would you respond to that?" I'd first say, I'm not the kind of doc you think I am, and a PhD doc, not a medical doc. So you should take everything I say with a grain of salt. I think that the question is what's the purpose of you're trying to lose weight, right? And is it because you want to lose weight really quickly to, for cosmetic reasons, to kind of fit into a wedding dress or something like that? And you're not really intending on doing it for health reasons for a long period of time. Yeah, I mean, I think that people have seen over and over again that you get much more rapid initial weight loss with a lower carb diet. And we see that. We see that in our studies all the time, right? Much more weight loss because a huge chunk of it is coming from fluid loss, right? And but fluid counts, right? It is, but it's weight and it is distributed on your body and you will see that effect very quickly. If you're asking a question of what is for health purposes, what's the best diet that I can go on? And for the next question that I would have is, well, you know, we actually don't throw everything else that we know about nutrition, right? You should probably eat lots of non-stargy vegetables, no matter what kind of diet that you go on. If you choose to eat a low carb diet, there's healthy ways for you to eat a low carb diet. And the most important thing is on any of these diets is whether or not you're going to be able to stick with it for a long period of time. And there are healthy ways to eat a low carb diet. There are healthy ways to eat a low fat diet. You have to eat a certain amount of protein. That's another topic of conversation about how much that is. And there are lots of choices within those different dietary patterns on how to eat a healthful diet. And what's happening inside your body from a weight loss perspective is I think much more interesting, metabolically and hormonally, what's going on inside your body on these two different dietary patterns. They both will probably lead to similar amounts of body fat loss over time. That's what the longer-term randomized control trials show. But inside your body, the hormonal and metabolic milieu will be very different. And I think that that's why the weight aspect has been a huge distraction. I mean, I think there's some really interesting data about how ketogenic diets help control glycemia in people who have prediabetes and diabetes. Is that sustainable over long periods of time? And does that really improve insulin sensitivity? There's some debate about those kinds of things. I think it's really important and interesting questions to discuss. How does it change overall states of inflammation and your immune system function? We actually partnered with some folks in the Imminology Institute at the NIH to look at those low carbon versus low fat diets and how they affect the innate and adaptive immune systems. Big differences even in two weeks. What the implications of that are over longer periods of time. I think are really interesting. How does it affect autoimmune disease? How does it affect other kinds of conditions of increased inflammation? I don't think we know the answers to those questions. So in some sense, I think that the most interesting questions on low carb versus low fat diets have yet to be answered. And you know, Christopher Palmer has been very interested in mental health aspects of these diets. Perfectly legitimate question. Right? I mean, you could imagine that your brain, you know, functioning on ketones for, you know, a good chunk of its energy expenditure as opposed to just glucose might have some effect on neural plasticity and neurodegeneration. I don't know. We don't have good data on that yet. So I think that this concept is always a question of for what purpose? Why do you want to do these diets for what purpose? And there's just still a lot of open questions about how the body responds, especially over longer periods of time. And it's challenging to do those kinds of studies without the sort of investment that has not been available to nutrition scientists for quite some time. Do these diets whichever way you go on average, if you go low fat or you go low carb in the real world, how well do they work over the long term? I don't know what the latest statistics are and the earlier ones were incredibly discouraging about when it came to just weight, right? So when it comes to weight, weight regain is incredibly common when people try to lose weight from a dietary perspective or a lifestyle perspective. Now, I think that the original statistics on that were really bleak. It was like above 90% of people who'd lost weight on a diet regained it. I don't think it's quite that bad. And there's certainly some people who do extremely well on lots of in different these different diet groups. And they will attribute their success to the dietary pattern as opposed to other things in their life, which might have been allowing them to kind of make these big changes. So that was one thing that was really interesting. Christopher Gardner did this amazing study called the Dietfit Study, which basically was a year-long randomized controlled trial. I was signing people to a low fat versus a low carb diet. And you see this variability that we talked about before, right? And it's really tempting to say that a big chunk of that variability is biological, right? Maybe there's some genetic basis that there's some responders to low carb diets and the responders to low fat diets. And my co-author in the book, Julia Ballouz, did a story at the time for Vox on that study and she went and interviewed some of the people who had had some success and others who had had not so much success in losing weight. And it turned out it's anecdotal, but the people that she happened to talk to who didn't have success were undergoing some major life change at the time like they lost a job or something like that. And the people who were successful were pretty stable in their careers and their families. And maybe that explains as much of the variability as biology. And I think that we underappreciate the social aspects potentially. Again, it's something that really does need to be studied. I have to also imagine you know, in fact, is like how supportive your family are when you come home and all of a sudden say you're going to cut cobs out. I'm going keto. Yeah, I'm going carnivore, no more vegetables in the house, right? I don't know. It would be interesting to see how much support that would have or versus the opposite, right? Yeah, no more no more me, no more. We're going extremely low fat vegan for the rest of the year that sort of family support system. I mean, you would imagine it has an effect, but I don't think that's been well studied or if it has, I'm not aware of the date on it. All right, just before we close things out here, coming back to I guess really the core of what we've been discussing, which is the food environment. RFK, Jr says that there will be a federal definition of ultra-process foods that's coming out imminently, I believe. And then there will be front of pack labeling to follow. That's what I've read anyway, but he's also said that he won't regulate these foods. It's more about informing people, educating the public. I'm interested given what your research shows about ultra-process foods as a broad category appreciating that they're not all the same and how they tend to override our kind of conscious decision making. We do say that is education is transparency, front of pack labeling is that enough or do you feel like significant regulation would be required to change the food environment? Again, it's not my particular field of expertise on policy, but my intuition from what Little Life understood about how successful policies have changed population level behavior in the past is that that sort of information alone is not enough. The examples that people tend to use are tobacco. Tobacco was a case where we certainly put labels on cigarettes as how they can cause cancer and death in heart disease. The biggest contributor to reducing smoking as best as I understand it was taxation, so increasing the price. That's a regulatory thing that was the most effective means of reducing smoking rates. Not that these other things aren't important and that you have to do many things at once. The difference that we have with food.
as compared to tobacco is that people need to eat something, and they need to be able to afford to eat something. And that something should be nutritious and healthy. And so there's a lot of discussion about, you know, removing ultra-process foods from SNAP, which is like the food stamps program. There's a lot of discussion about potentially increasing the price of ultra-process foods with taxes, although you're right to say that I don't, I think I've heard that from this administration, but some people believe that that should be the case. There's discussions about, you know, limiting marketing, especially to children, but in the US, that's sometimes problematic because of first amendment issues in the constitution and limiting free speech of companies. But what I have heard precious little talked about, which I think needs to be talked about, is not so much the punitive aspects, but how do we actually subsidize and make healthy alternatives as convenient, tasty, and available, and inexpensive to people to replace the harmful ultra-process products that are gonna be penalized? That aspect, I think, doesn't get enough attention. And what do those types of things need to look like? So for example, how do we incentivize food manufacturers to create healthy products that are convenient? They might end up being ultra-process. So for example, I used to give all the time was, I don't make my own marinara sauce. Because I can buy a marinara sauce that's low in sodium and low in sugar, it still tastes really good. It happens to have some preservatives in it that are cosmetic to make the color not degrade over time, that make it ultra-process, but from a nutritional perspective, I don't believe that that's an unhealthy food. And it makes making a whole grain pasta primavera a lot easier, right? It turns out that that product is more expensive than the sugar-laden version of a tomato sauce, right? And how do we switch that? How do we switch the economics of that? Because it is more expensive to produce that product. How do we potentially subsidize the healthier alternatives? What policies would we need to put in place to make that the case? Or how would we incentivize food companies to make those products more widely available? We have a whole chapter in our book about some ideas of how to do that. You could imagine the taxation is part of that and where the incentives are put in place in terms of the FDA has come up with a definition of what healthy is, right? And it's only currently being proposed to be an optional marketing aid for products that are healthy, but you could imagine using the same definition. And saying if a product is healthy by the current definition, which is based on previous dietary guidelines of recommendations, and it's not energy dense, and it's not hyper-palatable, then it might actually be beneficial. And if it doesn't meet those requirements, then it could be subjected to some sort of policy like attacks or something like that. How would we incentivize supermarkets, for example, if we could track the average healthy eating index of a grocery cart and basically incentivize supermarkets to improve the healthy eating index of the average grocery cart? What kind of pressure would that apply upstream to the purchasing on manufacturers to improve the healthfulness of their products? So there's several of these sorts of what we think are potential things that could move the needle to actually improve the availability of convenient and healthy products regardless of whether or not the ultra-process, because if we can pinpoint the mechanistic basis by which ultra-process foods are harmful, then those can be part of the policymaking decisions. They can also be part of the information systems that consumers have and also part of what manufacturers are engineering their foods around. Yeah, I love that distinction that you made between the tobacco industry and the food industry and that we have to eat. And because I think on this topic, you kind of run the risk of throwing the baby out with the bath water, just food companies bad, ultra-process food companies bad, and it oversimplifies what is a very complex problem of, we have to have food accessible to a large population of people of different socioeconomic backgrounds. And it deserves deeper kind of thought in terms of what that solution looks like. And I think it would be really neat if as a customer you went to the supermarket, like you said, and you bought all these products and like on your receipt, it kind of gave you a health, that score of how healthy your food was and maybe like a coupon or something for future purchase. Right, all right, yeah, your price of your basket maybe depended on your healthy eating index, right? It could be some way to do that and government could subsidize the supermarket in a way that would make that attractive to them, right? So yeah, I think that there's clever ways to start to think about policies that could really, instead of just focusing on being penalizing the foods that we think are harmful, which we should do. I think that we really should, you know, tax sodas, remove them from staff. I think we should do all those things, but that's not gonna be enough. We need to make healthier alternatives that I'm not talking about making twinkies a health food, right? I'm talking about reformulating something like pizza. So we talk about this in the book, you know, Mike Lean and Donnie McLean in the UK, basically redesigned pizza so that it matched the eat well guidelines. And it's more expensive, it's tasty. People like it, it's not scaled to the nation yet, but the point is is that you could actually, you know, redesign something like pizza so that it is more like a health food than its current versions and at least in US supermarkets. There's like an entire freezer section of pizzas that do not meet the same nutritional standards. And a modeling study that was published several years ago is that pizza is so often eaten in the US that just reformulating pizza could make a measurable difference in public health. Just that one food. Do you find that some people have a kind of a version to the word reformulation? And maybe here you're talking about like working with the food industry and sort of wrongly position you or misunderstand and see you as someone who's trying to protect the interests of the food industry. - Yeah, I mean, I certainly kind of felt that a little bit. I mean, no one's come out and said, you're a shell for the food industry and I've certainly haven't worked for the food industry. I don't work for the food industry. I've never accepted money from the food industry. I've been frustrated with the food industry, as I mentioned before, about their lack of willingness to participate in research. But I just think practically speaking, we're not gonna let all live on family farms again in subsistence farming unless civilization collapses, right? I mean, we shouldn't be planning for that. And if you have the wherewithal in the means and the interest and the skills to avoid ultra-process foods and have your personal chef and your backyard garden prepare all of your foods, more power to you. It's not gonna be harmful for your health, but I kind of live in the real world and I know that making that sort of shift in my family, I mean, maybe I'm lazy. I'm just not willing to do it, but I try to make these smaller changes. Like, okay, how do I make it easier to prepare a healthy meal for my family? How can I incorporate the healthiest versions of some of these products? And within my means, I can afford to pay a little bit more for that marinara sauce, right? I can afford to buy fresh vegetables to cut up, but I would, you know, someone else could buy frozen vegetables and that would be just as good or canned vegetables. Would be just as good, nutritionally speaking, at least from a practical standpoint. So how do we make it easier for people to eat better and still like the food that they're eating, right? I think that's the issue. Well, at the same time, disincentivizing the poor choices are making them a treat. Like, basically, I don't wanna eliminate people's favorite, you know, junk food, but it should be a treat, right? It should be treated as a recreational substance, as opposed to a daily habit, right? So that's the kind of flip of the food environment that we'd like to see and the question is, how do we get there? And what data do we need? What research do we need to kind of inform that, right? I mean, I think that everybody, you mentioned this earlier in the discussion that some people think we got all the answers and we don't need to anymore research to figure out how to do this. And I'm not one of those people. I think we actually do need more research and we've under-invested in nutrition science for a very, very long time. And I think that now is the time to really invest in that and coordinate nutrition science research with food science and technologists, as well as agricultural scientists. And because we're gonna have to be targeting, not again, just the next several years, but decades into the future. Speaking of more research and answering more questions, I know you've stepped down from your role at the NIH, but do you have any more interest to run experiments? - Yeah, no, I mean, definitely. I definitely do. And what capacity that will be is, I think, still an open question. Right now, I'm designing trials for a drug company to treat obesity. We have a pipeline of new kinds of categories of drugs to treat obesity that hopefully will improve upon what's currently on the marketplace. And I'm trying to design mechanistic studies to better understand how these drugs work earlier in the pipeline.
and thereby, you know, position those drugs better to help the most people possible and the right people. So, you know, it's not the same research, but it's still definitely in the space of obesity science and understanding how the body responds and how appetite is controlled and what the underlying biology is. So that's been a unique and interesting experience so far. I've been on the job for one month. So it's been a little bit of a culture shock stepping into Big Pharma. But, um, but yeah, I'm enjoying it so far and who knows if that's going to be right for me long term, but I'm, you know, interested in seeing where things go with that and maybe in the future, I'll have a lab in an academic department somewhere and we'll be doing more of the kinds of nutrition and metabolic science in obesity and people without obesity in the future. Is there any tension there in terms of the the kind of competing ideas or competing interests? If the food environment's cleaned up and less people are obese, is that reducing the demand for these medications? You know, I think a lot of people listening will be thinking, well, Big Pharma doesn't want the food in the food environment to be cleaned up because it's not in their interest. How do you as someone who's now sat in kind of in both areas? Both states, how do you reconcile that? To be honest, from again, I've been in Big Pharma for a very, very short period of time. They don't think about the food environment, to be honest with you. They are just trying to make the most efficacious and safe drugs that will treat the people who have, in fact, been most susceptible to these changes in the food environment and do it in a way that's better than their competitors and take more of the market share. There's a lot of people right now, like I said, I think I view these kinds of interventions, these pharmaceutical interventions as the bridge that's going to get us from the calorie glut and the food system that we currently have. In which we've been focusing solely on maximizing protein and calorie production to where we're going to have to end up in the next several decades with a food system that hopefully is a lot healthier and a lot more equitably distributed and is a lot healthier for the planet as well. And there's a lot of work that needs to go into both helping manage that bridge between now and then, which I think that these drugs are really helping and we can even do better in the future. And what it's going to look like when we hopefully all work together, these different sectors of the food industry that have not worked together very much in the past and as well as the nutrition scientists who need to play a role in that as well. And last question here, if you had unlimited funding to run another metabolic world study or if there's a nutrition scientist listening right now who has a grant, what study would be top of your list? What question are you kind of really wanting to answer? Yeah, I mean, it might not be a surprise given where I am now. I'm really interested in this question of what it is about our food environment that's interacting with our fundamental biology to regulate our body weights at very different places. And how is it that given the age of obesity pharmacotherapy that we have now, what is the interaction between the food environment and how these drugs work biologically that's giving rise to their effects? I think that that, you know, we're at a really interesting place in history, right? Where we have these huge shifts in our food environment and increasing exposure to, you know, what is it that we need to do to improve things while at the same time actually having effective treatments that appear to be safe so far for many people with obesity and lots of work to do there. And yet, we also know that, you know, it's this biological interaction with our environment that has driven the problem in the first place. How does the biological interaction between the pharmacotherapy and the shifting food system actually play out over time? I think that those are a fascinating set of research questions. I think the challenge is that currently there are very, very few facilities that have the capacity to actually effectively answer those questions in a period of time that's reasonable. So, for example, when I was at the NIH, I could maybe house two or three people at a time to do these studies. So doing a study that would last a month each and each of those people with only two or three people at a time, getting to 20 or 30 people takes years. There's no reason that that has to be the case. I think that we could scale that up quite dramatically and answer these questions much more quickly if we had those kinds of facilities. It's something that I was proposing before I left the NIH. It's something that I proposed after I left the NIH and briefly thought I was going to go back to the NIH to lead such an effort. Unfortunately, that didn't pan out. But, you know, someday I hope somebody will do that and we'll have that sort of capacity and be able to kind of answer these questions in a much more efficient way. Kevin, thank you so much for joining us today, as I said, at the top. It's a long time coming. So it's an honor to have this time with you and thank you for all of your contribution to science. Your studies have come up on this show in, I don't know how many episodes. So you've given us plenty to talk about it and think about I encourage everyone to go out and grab a copy of Food Intelligence, your new book, which I'll put a link to that in the show. Wonderful. Thanks for having me, Sam. There you have it, friends. I hope you enjoyed this episode. If you did and want to stay up to date with future episodes, be sure to hit that subscribe button on YouTube and follow on Apple or Spotify. Finally, thank you for showing up and the effort that you're making to take control of your health. I look forward to hanging out with you again in the next episode.
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