 Welcome to Ancestral Health Today, evolutionary insights into modern health. Have you struggled to maintain a healthy weight despite making great efforts? You're not alone. Since around 1970, the rates of overweight and obesity have skyrocketed in the US and other industrialized nations. Why is this happening and why is it so hard to lose weight? A good part of the explanation might lie in how the brain controls appetite and regulates weight. If we better understand how evolution has shaped the brain's response to food, we can look at how the modern food environment induces us to eat too much and figure out what we could do to change that. We'll be discussing these topics and more on this episode of Ancestral Health Today, a podcast providing evolutionary insights into modern health. I'm Todd Becker. We're talking today with Stefan Guine. Stefan is a neuroscientist who studied what drives many of us to overeat and become overweight, focusing on the role of brain circuits and how they respond to the food environment. He did his PhD in neurobiology at the University of Washington and he's spoken several times at the Ancestral Health Symposium. He's written a highly acclaimed book about this called The Hungry Brain. It's a great read and recently it got rave reviews in the New York Times. Welcome to the podcast, Stefan. Thanks for having me, Todd. So in today's episode, Stefan, we'd like to have you help us deconstruct the role that our brains play in eating and in overeating. And I'd like to start out by asking you to tell our audience what got you interested in studying neuroscience and the inner workings of the brain. Yeah, I've been interested in neuroscience from a very young age. It's one of the last remaining great scientific frontiers and it's the organ that more than any other makes us who we are as a species and as individuals. So I've always been fascinated in the brain. And studying the role of the brain in obesity has been also a great interest of mine. First of all, because obesity is a problem that affects so many people. It's so impactful. And also because it's something that I think the role of the brain in obesity is not necessarily intuitively obvious to people. So it presents a good opportunity for science communication. Yeah, it's a really fascinating area. And maybe before we get into the details around the brain, just reflect on the situation we're in today where if you go back and you studied hunter-gatherer type of societies and pre-industrial societies like the Katowins and even more recently our ancestors were not generally fat or overweight but now maybe what, more than a third of Americans are obese. So what do you think happened? Yeah, so first of all, let me give you the latest figures from the CDC. 43% of U.S. adults have obesity. So not just overweight, obesity. The lifetime risk of having obesity is over 50% now. So more than half of Americans are expected to have obesity at some point in their lives. Because if you think about the 43% statistic, that includes 18-year-olds, right? And those are probably people who are not as fat as they will eventually become on average. Even children, right, are starting to evidence more obesity. Oh yeah, I mean that's been going on for a long time. Yeah, I mean the childhood obesity rate, it depends on what age group you look at but something like 17% have obesity. And yeah, so if you think about how that sets someone up for life, it's pretty concerning. And yeah, so if you look back historically, you see that obesity rates tended to be lower both in the United States, just 40 years ago there was a lot less obesity and then if you go back further than that there was even less to where it was actually pretty uncommon about 120 years ago in the U.S. And then if you look at non-industrialized societies, you see that typically there's very little obesity. I mean, I'm not going to say that it's non-existent but in most of the societies that I've seen evidence on, it's pretty uncommon to have even a single individual with obesity. Like you look at the Hadza hunter-gatherers in Tanzania, there's no, as far as I know, there's no traditionally living Hadza person who has obesity. You look on the island of Katava, there's no traditionally living Katavan who was studied by Stoff and Lindeberg that has obesity. Not even a single one that had overweight, in fact, or maybe there were a couple that were slightly over the threshold for overweight. So it's not that no one, it's not that everyone, you know, ancestrally had what we would consider an ideal body proportions today. It's not like they were all supermodels and bodybuilders but in terms of obesity, in terms of having a large amount of excess body fat mass, that was not the typical human condition historically as far as we can tell. And even in American society or Western society up until 60s, 70s, right, it wasn't outrageously prevalent. So what happened in the 70s and 80s? Why did the curve start to move up? And before you answer, you know, within this ancestral community, there's a lot of theories, right? There's many different theories. One of them is based on macronutrients, we're eating too many carbohydrates or refined carbohydrates or saturated fat or one of the latest is seed oils. That could be a mismatch, right? Because you could say those weren't around during these long periods of human and pre-human evolution. But do you buy that idea? Is that a valid source of mismatch or do you think it's something else? Yeah, so let me just say a couple of framing things first. The first thing I want to say is that we don't have randomized trials where we rerun U.S. history with the variables different. So a lot of what we're doing is guesswork based on bodies of evidence that we're kind of trying to indirectly apply to this situation. So there's a lot of uncertainty about this and anything that we say about it is going to be necessarily somewhat speculative, including what I'm going to say. And this is me doing my best to put the pieces together, but I don't want people to think this is like the gospel coming down from heaven and the concrete truth. This is just my best attempt to explain what happened. And then the other point I want to make is that a lot of these explanations are not mutually exclusive. So, you know, just on a pure logic level, many things could be true at once, right? So you could have, you know, it could be somewhat due to carbs and chemical contaminant and a virus. And like there could be 10 different things and that would be logically possible. And so I just want to acknowledge that it doesn't have to be just one thing necessarily. I'm glad you say that because there's a lot of folks out there who are sure that it's one thing, right? It's got to be seed oil, so it's got to be sugar. Yeah. But you're right. It could be it's most likely multifactorial, but still there's this inflection point, right? Yeah. How do you explain that? Yeah. So I think that essentially what we've seen is over time there has been a gradual but profound change in how we interact with food. And the big picture is that we have outsourced the preparation of food to restaurants and the food industry. And you see this in the data, we're spending way more of our money on food eaten outside the home than we used to. And that I think even underestimates the change because a lot of the food that we're eating at home today is processed food, whereas it would have been cooked from scratch 50, 100 years ago. And so that's kind of like the longer term context. And if you look at what happened in the kind of like late 70s, early 80s, what you see is proliferation of kind of between meal eating options, like processed food that people are eating between meals as snacks. And that includes sugar, sweetened beverages, by the way, which is kind of its own thing. And what you see is that people are eating a lot more snacks. And these tend to be processed, you know, sweet and savory foods and sweetened beverages. And then you see that calorie intake goes up at that time. And so I think, you know, one explanation for the increase in calories that I think is compelling is we're having more eating occasions, we're eating more processed foods, we're kind of swimming in this more abundant food environment with food options at all times a day that weren't necessarily available or socially sanctioned prior to that. And our calorie intake goes up. And that, you know, some people have pointed to the macronutrient composition. It is true that carbohydrate went up more than the other macronutrients. So it was primarily carbohydrate, calories went up. But, you know, if we're asking like, was it the carbohydrate specifically? Did that play a special role? I think that is kind of hard to square with the historical evidence because the amount of carbohydrate that we eat right now is not historically unprecedented. If you go back 100 years, we were eating about the same amount of carbohydrate and I think actually somewhat more. And it wasn't whole grains either. It was white flour mostly. And essentially what happened was in the mid 1800s, there were a series of technological advances that made the production and refining of wheat much, much more efficient. So things like advances in plow technology, the advent of tractors, mechanical tractors. The advances in milling technology, advances in transportation, like the railway system that allowed wheat to be transported from long distances. And so there were all these advances that basically made white flour go from a luxury item to absolutely dirt cheap, like the cheapest thing you could get. But it was still viewed as a luxury item. That was like what rich people ate. And so people were glad to shift their diets to this luxurious, delicious food and they were eating a ton of white flour, a lot more than we eat today actually. It peaked around 1900 and the amount of sugar they were eating was actually pretty substantial too. Not quite as much as today, but it had already increased most of the way that it was going to increase by that time. So people were eating this really carb-heavy refined carb diet at that time and it wasn't good for them by the way. They had nutritional deficiencies, their teeth were falling out. This was prior to fortification. So it wasn't healthy, but there wasn't an obesity epidemic either. And so I think that the idea that it's just about the carbs or just about the refined carbs is pretty hard to square with historical evidence. That said, I do think that carbs are part of the reason why we grow fat. So I don't think that it's nothing. I just think that they don't necessarily play an outside role relative to dietary fat. So you mentioned refining of carbohydrates. There's also refining of oils and seed oils and some have pointed to that and the uptick in Omega-6 as a driver. Do you think that's significant? Yeah, I think this is another one that's kind of complicated because this is another one where, like with carbohydrate, it can impact body fatness. So carbohydrate, we know low-carb diets can cause weight loss, so obviously it can impact body fatness and it's the same way with seed oils, at least in animal studies. If you reduce linoleic acid, the primary Omega-6 polyunsaturated fat in seed oils, you reduce it to a low level, like 1% or below in the diet of rodents. It does attenuate their fat gain on a fattening diet. So it's one of these things where there are biological effects. It's not like there's nothing at all to the story. But at the same time, there's this kind of narrative that has emerged that, by the way, I contributed to a decade ago that we evolved in this ancestral context with a really low linoleic acid intake and that now we're eating a lot and that is the driver of our health problems and obesity. And I think that that narrative just doesn't really hold up because there are ancestral populations that have a relatively high intake of linoleic acid. And if you look at, for example, the Kung San foragers of Botswana, that's one of the best characterized hunter-gatherer populations. One of the main articles of their diet was mongongo nut and you look up mongongo nut and it's got a lot of linoleic acid in it. And then you look up, there were populations, I don't know as much about these populations' health, but there were populations that ate a lot of pine nuts in the United States or in what currently is the United States in North America. There were Native American populations who relied heavily on pine nuts. Those are also high in linoleic acid. So this narrative that, ancestrally, we had this consistently low linoleic acid diet that we're adapted to, I think is pretty hard to square with the evidence. I think we just had a variety of different diets and sometimes it was high, sometimes it was low. And you pointed out the odds I had high carbohydrate diet, right? It was maybe less processed and they had to work for it. So let's get to, I think, something that comes up in your book, The Hungry Brain, which is a key factor here, which is that we didn't just all of a sudden just decide to choose to, well, let's just start eating more, right? Or let's eat more snacks. There was something driving this and you point to this idea of food cravings and that there's something about the food itself that's driving those cravings. Can you see more about that? And first of all, what is a craving? How does it different than generalized hunger and what's driving those cravings? Yeah, so I'm going to dive into this and tie it into some of the previous stuff we've been discussing here, because if it's not the linoleic acid, then what is it about seed oils that might be driving our intake? And I think basically it's that fats in general, including seed oils are brought together in delectable combinations that really stimulate the motivational circuits in our brains. So if you, at a really simple fundamental level, if you just ask the question, what makes a rodent overeat? Well, like how can you get a rodent to overeat as much as possible? And the answer is calorie dense, tasty human food. You just go to the grocery store, you buy tasty human food like cookies and salami and French fries and stuff like that. And you put a variety of it in their cage at all times and they'll eat a bunch of it and get super fat and they will ignore healthier food. In fact, can you just give us a little bit of insight into this observation that I think it was Anthony Sclafini had where he was trying to get rats to become obese on some kind of rat chow and failing. And he had this chance discovery. Can you say, you know, what happened there? Yeah. So in the 1970s, this was kind of a landmark discovery in obesity research. In the 1970s, at that time, you know, there was obesity. It was less prevalent than today, but it was still, you know, a health problem that existed in society and researchers were trying to study it. And they were trying to do it in various ways. A common way was you would add fat to their normal chow. And that the animals would gain weight, but it was slower and less reliable of a method of weight gain than they wanted. You know, if you have these experimental models, you want them to get, if you're studying obesity, you want them to get really fat, really fast. Otherwise, it's inefficient, you know. And they weren't able to do that, right? They were having problems getting the rats. And so, yeah. And so one day, Anthony Sclafini was in the lab. This was back in the day when rats were just kind of around in the lab instead of locked in these intense facilities. And there was a rat on the lab bench. And there was also a bowl of fruit loops that I guess another graduate student must have been eating. And so fruit loops for anyone who doesn't know, it's like this sugary breakfast cereal that has a kind of like fruity flavor. And the rat walked over to the fruit loops and started eating it voraciously. And this was really a strange, unexpected observation because usually rats have this thing called neophobia where they are really wary of new foods. They'll need a little bit, see if it makes them sick. And then if it doesn't, then they'll go back and eat more. But the rat was just chowing down on these fruit loops. And it occurred to Sclafini that maybe a way to make these animals fat would be to go to the grocery store and buy a variety of tasty human foods, things that humans like to eat and put it in their cages. And that's what he did. And the results were spectacular. So their calorie intake went way up. Their body fatness increased rapidly. And you could give them an enriched environment with lots of toys and stuff and cool things to do. That didn't stop the obesity. You could put a running wheel in their cage so they would exercise. And that made them gain less fat, but they still got quite fat. Was there any difference in the macronutrient composition of the fruit loops or any of these other supermarket foods? Or was there something else about those foods? Yeah. So this is a key question. And so for this, you have to look at other experiments where there's one in particular that I like where they actually manipulated. They compared side by side in mice, the cafeteria diet, which is what I just described, versus a diet that's high in fat versus a diet that's high in sugar. And what they found was that the animals gained weight on the high fat refined diet and the high sugar refined diet, but not nearly as much as on the cafeteria diet. And calorie intake was also not as high. So basically, there is nothing you can do to a rodent pellet that makes it as fattening as tasty human food. There's no macronutrient combination. There's no amount of sugar. There's no amount or type of fat that you can put into a rodent pellet that makes it as fattening as a variety of highly palatable calorie dense human foods. Okay. So what is it about these calorie dense human foods from the supermarket or from the cafeteria that makes rats and presumably humans want to eat them more than the same macronutrients synthetically put together? Yeah. So first, let me acknowledge that I don't want to say that manipulating the nutrients in the food doesn't have any effect. I don't want people to come away with that. I'm just trying to emphasize that it is not as fattening as human highly palatable calorie dense food. So there's something that can't, there is a portion of the effect that cannot be explained by just the nutrient composition of the food. And it's a pretty substantial portion actually. Yeah. So I think essentially what you see is their calorie intake goes up. So the question is what is causing them to have increased eating drive relative to these processed pellets? And I think there are a few different answers to that. One of them that you were kind of hinting at earlier is this heightened reward drive. So certain types of foods, certain combinations of nutrients stimulate dopamine release in the brain more than others. And basically highly processed taste of human foods are optimized to increase dopamine release. Not explicitly, but just by selection for what is successful on the shelves. The things that sell are the things that reinforce purchase and consumption behavior, which almost by definition are the things that stimulate our dopamine. And so you have these foods that are very stimulating to food reward circuits in the brain, motivational circuits that increase our eating drive independent of energy needs. And that is one of the things that stimulates, that I think probably stimulates these animals to over consume. And then another thing is sensory specific satiety. So this is a term that I think was coined by Barbara Rolls nutrition researcher. And essentially it's the concept that we can get full on foods that have a certain sensory profile, like a certain taste, but not full on foods that don't have that sensory profile. So for example, if you have a meal of steak and potatoes and salad, you can eat until you're full on those things. And then if somebody brings out another steak, you're not going to eat more steak. But if they bring out ice cream or a brownie or cookies, you're prepared to eat that different type of food. On the other hand, I call that the second stomach, right? Yeah. It's almost like you have a different thing you can fill. So why is that? Why do you fill up on the steak and then you still have room for the dessert? Yeah. So I mean, I think there's basically two explanations. One of them is sensory specific satiety. So we experience satiety or fullness relative to specific sensory properties of food. So the brain is kind of like, you know, I've had enough of this particular food, but that doesn't mean I haven't had enough of this other food. And so that's something that drives us to overeat a lot at buffet is because there are foods that have a variety of sensory properties. You know, every other bite, you've got a different sensory experience. And so you don't hit sensory satiety for sensory specific satiety for a long time and you end up over consuming. And you see in rodent studies, the variety per se when you do controlled experiments does impact their calorie intake and body fatness. And it's pretty substantial. So if you had just one calorie dense, palatable human food in the cage, you're not going to get the same effect as if you have a variety of calorie dense, palatable foods. Palatable foods. In terms of, yeah, the fattening effect in rodents. Stefan, you're using this term palatability, suggesting there's something about the food itself, right? So what is it about foods that make them palatable? Is this an innate thing? Is it learned? And if it's learned, can it vary between cultures and people? Or is there an inherent property of these foods that innately appeals to us humans? Yeah, it's both. And let me take a little step back and talk about palatability and what it means and what its importance is. Palatability is just how good a food tastes. And I use that term a lot because it's a term that people understand. But the real concept that I think is more important is our motivational drive to eat. And that is something that is correlated usually with palatability, but it's not perfectly correlated. But that's really what I am interested in mostly is that dopamine release and the motivational drive and the learning, eating behaviors and habits that it causes. So I use palatability again just kind of for its communication value. But what I'm really talking about is that motivational drive that's distinct from the conscious experience of pleasure, which is what palatability means, although they usually operate together. So having explained that, essentially there are specific food properties that the brain is hardwired to be motivated by and to release dopamine in response to. And the ones that are either known or strongly suspected are carbohydrate, including starch and sugar, fat and protein and salt and umami glutamate, which is that umami meaty flavor in soy sauce and cooked meats and things. So those are things that the brain innately responds to everyone or almost anyone from any culture will enjoy those food properties. But through the process of conditioning, Pavlovian conditioning to be precise, we learn to prefer, we learn to like things that are associated with those properties. So if you eat, let's say, strong cheeses, let's say you grow up eating strong cheeses, let's say you grow up in France. Your brain comes to associate the taste and the texture and the appearance and the aroma of that cheese with the concentrated fat and salt and protein that it delivers. And once your brain makes that association through dopamine mediated reinforcement, then you come to enjoy and be motivated by those sensory qualities. So even the aroma before you've put it in your mouth, the aroma of the cinnamon bun or even the appearance of the cheese can all of a sudden start those circuits firing up. Exactly. Yeah. So what happens is the dopamine release, initially it happens when you consume the food, but over time the dopamine release comes to be associated with those sensory cues. And so when you see the cheese or you smell it or you smell the brownies coming out of the oven or you're in a situation where you would normally have pizza with your colleagues or a beer or something like that, that's when the dopamine starts firing and that's when your motivation gets triggered and you experience the craving for that item. So it's the dopamine response gets transferred onto the sensory predictors, the predictors of those nutrients. And that's kind of how the brain works and that's how cravings work. So eventually the things that predict the receipt of those nutrients are the things that stimulate your motivational drive and cause you to experience a craving. So going back to evolution, obviously this is not a malfunction. This is a feature, not a bug, right? Obviously our ancestors, hunter-gatherers, it was useful to pick up cues that there might be gained there or berries there. So it's not a defect, but how is it then coming back to the modern mismatch? What's gone wrong in that cue signaling that's driven cravings to the point where people overeat? Because it existed already in our ancestors, right? Yeah, and it existed long before humans existed. These brain structures that regulate this go all the way back to lamprey as before the evolution of most of the types of fish that we know today. So this is extremely deep. And as you said, it's not a malfunction. It's how our brains are designed to operate. This is the process that happens even when we eat healthy foods. But the problem is that the system gets overstimulated with modern, highly processed foods. And essentially what we have done over the course of history through the progress of technology and affluence, we have become better and better at extracting and recombining the, quote, active ingredients, the active dopamine releasing ingredients in food. So it's more concentrated now. Yeah. So, you know, it used to be that humans would get salt from whole foods or maybe sometimes from sea water or from blood. And now we have 100% pure salt in unlimited quantities to add to anything we want. Sugar is the same way. You used to be able to get it from fruit or honey. Honey is pretty concentrated. But now we have it in 100% concentrated form to add to anything we want. You know, glutamate. That's another one that umami flavor. Processed food is full of that stuff. And usually it won't say monosodium glutamate. It'll say like yeast extract or some other thing. Hydro-hydrolyzed vegetable protein. Yeah, yeah. Same thing. It'll be something where it's the same thing, but it's not something you would recognize in the ingredients list. But it's still, you know, the same compound doing the same thing to your brain. And so, yeah, so everywhere you look, essentially we have mastered the active ingredients, quote, unquote, in food and recombine them to maximally stimulate our own palate. And so we are surrounded by food that is simply more tempting than what our ancestors would have experienced. And that's not to say that they never ate anything tasty. Sometimes they did, you know, like there was honey, there were fruit, there was meat. Sometimes the meat was fatty, so it's not like there were never anything that tasted good at all. But it just wasn't available in this concentrated form, right? Yeah. So there was no way to, yeah. Yeah. And you think about the meat, for example, which is probably one of the tastier things they would eat. Most of these cultures didn't have salt. So you're not salting it, you're not putting herbs all over it. You're cooking it the best you can over an open fire, and some parts are burned, some parts are raw. And, you know, it's not up to modern cuisine standards, even the stuff that would have been relatively tasty. So basically we've just like through all of the methods, cooking methods and extracting ingredients and, you know, absolutely abundant availability of everything, we've just kind of like optimized the entertainment of our own palates. So we're getting an abnormal secretion of dopamine in response to these hyper-palatable foods. And you've mentioned dopamine now several times here. In the popular press, the word dopamine is thrown around, you know, all the time. You know, all addictions come down to dopamine, whether it's smartphones or sex or gambling or anything else. But, you know, what is dopamine? Can you say more about that and how does that work in the brain? Is dopamine about pleasure? You've used the term reward, you know? And does dopamine happen before you eat or after you eat? So say more about dopamine. What is it and how does it work in our brain? Yeah, so dopamine is a neurotransmitter that is involved in motivation and learning. And it is often associated with pleasure in the popular press, but that's not well supported by the evidence. So dopamine is really a learning and motivation chemical. And it does absolutely play a critical central role in those processes. And particularly that kind of like visceral, craving level motivation. I'm not talking about the kind of motivation where you're like, man, I should really put my shoes on and go for a jog right now. And I'm going to force myself to do it. That's not the kind of motivation I'm talking about. I'm talking about the kind where you have to force yourself not to do it. There's a slice of pizza in front of you and you're smelling it and you're like, I really shouldn't have another one. That's the kind of motivation we're talking about. More of a visceral, craving level. So the dopamine happens before you acquire the object of your desire or it happens after. When does dopamine go up? Yeah, so it's an incredibly elegant system. And to walk you through that because there's not a yes or no answer to that. So to walk you through that, I'll take you through a hypothetical example. Let's go through Ivan Pavlov's experiment because I think that really can illustrate this well. And Pavlov did his research before. We knew what dopamine was. But now we know what role dopamine plays in this sort of thing. So what Pavlov did is he noticed that when he would come in to feed the dogs that he would do his experiments with, they would start salivating like crazy. So they would start drooling. And so they were experiencing behavioral and physiological activation in preparation for ingestion of that food. And that food is what's called an unconditioned stimulus. So that means they innately have a motivational response to that food. Now what he showed subsequently was if he just rang a bell, it was a meaningless stimulus if he just rang a bell. And the dogs didn't really respond to it, meaningless stimulus. However, if he started ringing the bell at the same time that he gave them food, eventually the dogs would come to salivate and have that anticipatory behavioral and physiological response in response to the bell itself. They made the association with me. Yeah, okay. And so what happens there is initially the dopamine is associated with the food. It's getting released with the food. But as that association forms, as the brain comes to understand that the bell is a reliable predictor of the food, the dopamine signal transfers over to the bell. And so it's no longer being released with the food, it's being released with the bell. And so essentially, and it gets a little bit more complicated than that because dopamine essentially, it tunes your brain to the value of the item that it's responding to. So if you ring the bell, then they get the dopamine response and then you bring the food out. But if that food is not as good as it usually is, if the food is not as rewarding as usual, there will actually be a negative dopamine response as they eat the food. A disappointment. The dopamine will actually drop. Right. Yeah, exactly. And if the food is better than usual, there'll be a bump in the dopamine as they eat the food. And that retunes for next time, retunes how intense their motivational drive should be when they hear that bell. And so maybe if the food is consistently bad after the bell, then maybe they won't salivate as much, won't get as excited about it over time, they'll tune the strength of their association. But if the food is always the same, then there's no tuning that happens when they actually receive the food and there's no change in dopamine. And they just get this bump when the bell rings. Okay. So you form this association and the more you then experience this cue, the bell or the aroma of the bun or whatever, that dopamine comes back and it keeps getting reinforced. Once you've consumed the food, it goes away. So is it really just the buildup that teaches you to pursue the food or does do you get a lingering pleasure afterward and the dopamine stays high? Well, initially, if you're eating a new food that you've never had before, then, and it has a lot of, let's say, fat and carbohydrate together, which seems to stimulate a particularly powerful dopamine response. If you're having that for the first time, then you're going to get a big dopamine burst when you consume that food. And that is teaching your brain that that's a really valuable food. But over time, when you have that multiple times, that dopamine is going to transfer onto the sensory cues, like the smell of it, the appearance of it, things that predict it. But at that point, it's already been stamped into your brain that that's a highly valuable motivating food. And the only thing that's going to change that is if you then consume that food again and it's either better or worse than your expectation. And then dopamine will retune your motivation level at the time of consumption. So you can... Does that make sense? Yes. Or also if you... How about if you don't experience the cue for a long time, will there be a fading or extinction effect too? Yes. Or will it just stay there? No, there is a fading that happens. And I don't know... I would guess that that does relate to lower dopamine response over time. I don't know whether research, probably research has been done on that. I haven't looked into it. But certainly on a behavioral and motivational level, yes, there is a forgetting that happens. And those motivational circuits will weaken over time. Just to give an analogy that I think is helpful that most people will have at least some familiarity with. If someone is addicted to cigarettes and they're trying to quit, they're having a strong... Those cigarettes have been strongly dopamine reinforced. And so they have this strong behavioral drive and craving to smoke cigarettes. When they stop smoking cigarettes, initially they're going to have really strong cravings to continue smoking cigarettes. But if you don't smoke for a week, the cravings are going to diminish. And if you don't smoke for a month, they're going to diminish even more. And then by the time you haven't smoked for a year, you probably won't even want to smoke at all. You probably think it's gross. And so there is this process of forgetting that happens with these dopamine-reinforced stimuli. And that happens with food as well. So can we use this to... So you've said that these sort of supernormal stimuli in our current diet ramp up the reinforcement, ramp up the dopamine. Can we use this knowledge to decondition or to extinguish this by avoiding these foods and eating, I think you've used the term bland, a blander or less palatable food. It doesn't have to be boring. But can we actually get on a different path by understanding this? Yeah. And I think there are a variety of different ways of doing this. And I think most popular weight loss diets actually are already leveraging this to some degree. Because one of the key killer elements for stimulating dopamine is combining carbs and fat together. That really gets the circuits going. And what we see is that people who go on low carb or low fat diets tend to eat less and lose weight as a result without having to necessarily deliberately restrict their calorie intake. Their appetites just naturally diminish and they lose weight. And if obesity were all about one macronutrient, then you would expect to see one of those diets making people gain weight and the other people losing weight. And really what seems to be the case is eating both abundantly is super fattening and taking out either one is slimming. And I think the most obvious explanation for that is the food reward idea that it's really the combination that is the problem because it stimulates our motivational circuits to eat. And so go ahead. So that's separating out the individual ingredients, but there's also the component of flavor too. So less palatable can be just dialing down the flavor itself. And going back to these observations from Sclifani, breaking that flavor calorie association, you probably remember Seth Roberts who was active in ancestral health society. And he had this funny diet called Shangri-La diet. Just eat calories with very little flavor or a flavor with very little calories. And it actually, I tried it, it does work. I don't know how sustainable it is. But generalizing that a little bit more, making sure that you don't have a flavor bomb in combination with the calories. Does that make some sense to you? Or is it just about the calorie combination? I mean, ultimately it comes down to how many calories you're eating, I think. But what's the most sustainable path to that, I think, is the question. And I think you can envision different ways of controlling your calorie intake that are either trying to work with these non-conscious brain systems or are pitting different brain systems against one another. So the calorie counting approach is kind of taking your conscious rational brain and pitting it against your appetite circuits and other non-conscious circuits that are trying to get you to eat more. So I would say that working on lowering the reward value of your diet is more trying to recruit those non-conscious circuits to support your conscious goals. So I think that controlling or limiting the reward value of the diet is one lever that you can use. It's not the only lever that you can use to control appetite, but it is a lever. And I think it's something that people can experiment with. I think different people are going to respond better or worse to it. But I think it's a tool in the toolbox. I'll put it that way. Yeah. So looking at diets then and applying this, do you have a favored diet? Do you have an opinion about paleo, keto, or low-fat, or vegan, or Mediterranean? Do you think any of them could, in principle, work or is there one that you gravitate toward based on that? In terms of weight control? And also this understanding of appetite? Yeah. So I think, you know, I'm also very kind of pragmatic and empirical about this stuff. There have been a lot of studies that have been done on weight loss diets, and there are a lot of data we can look at. So part of it is just what does the evidence say about what diets cause weight loss and how sustainable are they in the average person? And I think that, you know, the first thing to acknowledge is that weight loss diets are not super effective in the average person. So the average person is not going from having obesity to being lean with these diets. It's more like, you know, 10 pounds of weight loss at the one-year mark. Usually people will lose more around the six-month, and then they'll regain some of it, and maybe they're 10 pounds down on average. And part of that's just adherence. Like people generally have a hard time sticking to any diet for more than a few months. You know, they just go back to their old preferences and habits, and they might be struggling against appetite issues as well. So, but if you look at the evidence that's been published, I mean, basically you can use a wide variety of different diets and lose weight. Low carb diets are some of the most effective. Higher protein diets are effective. Low fat diets are effective. And there's been less. So I would say if we're going from first principles, what diet is going to kind of maximize some of the properties that I think are important for a weight loss diet, I would point toward the, like, old school, cordane-style paleo as a really good contender. And can you define that a little bit more? Is that a... Yeah, I will. Yeah. And I want to say that there's not a lot of really high-quality empirical evidence on that. So I just want to acknowledge that. I think based on the principles, I would expect it to be one of the more effective diets, but we don't have really solid randomized controlled trial evidence demonstrating the long-run impacts. So, cordane-style is higher protein. It's based on unrefined omnivorous diet. It's low-ish in carbohydrate, but it's not particularly low in carbohydrate. I think it's... I don't remember exactly off the top of my head, but I think it's something like 30% carbohydrate calories. And then the fat component focusing on unrefined fats and more unsaturated fats. And so just to list also some of the things that it doesn't contain or de-emphasizes processed foods of any kind, sugar sweetened beverages, dietary salt, grains, both refined and unrefined, and legumes like beans and peas. So that's an overview of what the diet is. And the properties that I think are important in terms of weight control, the higher protein, the lower calorie density that comes from eating whole, water-rich and fiber-rich and protein-rich foods. The moderate palatability that you get from eating whole foods and not eating much salt and not eating these super-processed, craveable foods like chips and pizza and things. So I think there's a combination of factors in that diet that I think should tend to promote weight control better than your average diet, kind of on first principles. That's what I think. But again, I do wish the empirical evidence was stronger. No, good point. And it sounds like it's for a combination of reasons. Some of it is the relationship to appetite stimulation that we've talked about for most of this podcast. But there's other factors relating to the macronutrients and their interaction with our energy balance systems, hormones like leptin, insulin, things like that as well, that we haven't really discussed. So would you say it's both the impact on the reward circuitry but also other factors that also enter in? Yeah, reward and satiety, I think, are two big ones. I want to say, yeah, so just to unpack the satiety thing a little bit to make sure that people are following, I mean fullness, so how full you're feeling, particularly per calorie that you're eating. So foods differ greatly in how much satiety they cause per calorie that you're eating. And if you have lower calorie density, higher protein, higher fiber foods, you're going to get more satiety per calorie, and that will cause you to naturally terminate your meal having eaten fewer calories but still feeling satisfied. And if you look at the weight loss drugs that have been really successful, the most successful, including the ones currently that are doing so well, what you see is they generally are targeting both appetite like the hunger piece, the satiety piece, and the reward piece. So the most effective weight loss drugs are targeting both. And I tend to think that the most effective diets are also going to target both of those. Both systems, right, great. Well, Stefan, this has been a great conversation, I've learned a lot, could get into so many more aspects even within the brain. We didn't even really get into the anatomy of the brain, but we talked about some of the reward circuits. We talked about the relationship between contemporary diets and how we evolved. So it's been great. And before we end, I'd like to just give you a chance to talk about what are you working on these days and where can listeners go to learn more about your work? Yeah, in terms of science communication, a lot of what I've been working on has been related to nutrition misinformation lately. So I just published an article in Asterisk magazine about nutrition misinformation. That is kind of my attempt to wrap my own head around it and understand how common it is, how impactful it is, and communicate that to other people. So anyone who's interested in nutrition misinformation, check that out. Also related to that is I'm the director of a nonprofit called Red Pen Reviews that publishes free reviews, free expert reviews of popular nutrition books. And so we're really trying to give readers the tools they need to understand what the information quality is of the nutrition information they're consuming. So that's something else that I'm working on. And my website is SteffenGinae.com. I haven't been publishing there much lately. I'm mostly on Twitter at S-Ginae. Great. Well, thanks so much for talking with us today. And good luck with your current endeavors. It's been a pleasure. OK, thanks for having me. All right. Thank you. Thanks for joining us on this episode of Ancestral Health Today. We hope you enjoyed our discussion on how evolutionary insights can inform modern health practices. Be sure to subscribe to our podcast to catch future episodes.