The Hungry Brain: How and Why Your Brain is Undermining Your Weight Goals - An Interview With Dr. Stephan Guyenet

What follows is a transcript for the podcast Weight Loss - Dr. Stephan Guyenet - Neuroscience.

Topics within the interview include:

• Can we change our weight set point?
• The role of dopamine in flavor learning.
• What an fMRI experience reveals about food cravings.
• Easy to implement tips to outsmart the hungry brain.

Dr. Greg Kelly: Hi, this is Dr. Greg Kelly, Senior Director of Research and Development at Qualia and today's host for Collective Insights. Today we have as our guest, Dr. Stephan Guyenet. He's a neuroscientist who has spent a total of 12 years in the neuroscience research world studying neurodegenerative disease and the neuroscience of body fatness. Stephan is the author of the book, The Hungry Brain, and our book club recommendation for this month, and founder and director of Red Pen Reviews. Stephan, welcome to the show.

Dr. Stephan J. Guyenet: Thanks for having me on, Greg.

Dr. Greg Kelly: Oh, it's definitely my pleasure. I've read your book, I've recommended it to other people on our team, and it's the reason we're going to use it as a kickoff for our what will eventually be a continuing series of basically book club events. And one of the reasons I thought your book was perfect for this goes back, I think it was the very first review I happened upon of your book, mentioned essentially it's a great book on diet, does a better job on nutrition than other nutrition books, and it's also one, if not the best books on the brain, on neuroscience, even though it's not per se, a book on that. And since our audience loves the brain, loves things to do with health, I thought you would just be the perfect book and author to start this series off.

The Hungry Brain: How and Why Your Brain is Undermining Your Weight Goals

Dr. Stephan J. Guyenet: Yeah, thank you. Yeah, it's kind of interesting because one of my goals with the book, which I think was a pretty ambitious goal, was to understand and communicate kind of the entire circuit that links inputs into the brain to eating behavior outputs of the brain. So what are the signals that the brain is taking in, and then how is it processing those through and how is that leading to eating behavior? And essentially, if you understand that, then you understand a lot about how the brain works in general. So it does have a component of general neuroscience.

Dr. Greg Kelly: Well, and since you mentioned it, what was, I guess the inspiration for writing the book? I know I'd seen you in some, I think pretty prominent debates is taking almost what I think of as the neuroscience position about how the brain regulates weight. But what was that the reason that you'd already made somewhat of a, I guess, position in the industry being an expert in this?

Dr. Stephan J. Guyenet: Well, I think having a platform was certainly part of it that made it easier for me to get a book deal. But the main thing for me was that I felt like I had a really interesting idea to communicate. And it's not my idea, the big picture is something that was put together by the neuroscience community with some small contributions from my research. But these were ideas that the neuroscience research community was publishing in scientific journals that were not making it to the public. And specifically the field of neuroscience of obesity was publishing evidence that I think is really pertinent for understanding the determinants of eating behavior, the determinants of over consumption and the determinants of obesity. And in my opinion, neuroscience is the field that has provided the greatest insight into how those things happen. And most of that information wasn't making it to the public.

So I'm sitting here in this field just soaking up all this really cool evidence that is so informative of why we have the eating behavior that we have and why we gain more fat than we would like to, and I'm just not seeing any public awareness of that evidence. And so I consider myself to be lucky that I was the person who was able to write this book, to pull together all of these insights from around my field and related fields and put them into a form that is understandable for the public. So basically my inspiration was being in a place where I felt like I had significant understanding from being in the field that I was in. And I didn't see that understanding trickling to the public. I felt like I was in a good position to be the person to communicate that because I'd been writing for a while, I had some writing skills and I had a platform.

Dr. Greg Kelly: Well, I know maybe, I mean, there's lots of areas that are misunderstood when it comes to health, but I think weight's one. I guess an analogy that I've used, and this comes from being fairly height challenged. So all my siblings, cousins are much taller than I am. I'm the short one in the family. And I've never spent a day thinking about, geez, what can I do to be taller? But we accept whatever our height is, it's been chosen for us. But with weight, I think one of the areas that's been misunderstood, not in your field and with your book, is that we tend to think that weight is way more changeable. I mean, clearly it's changeable in the sense that people gradually tend to accumulate more and more of it. But it's not height, it's not unchangeable. But I think the strategies people have often either been told, kind of we could say, eat less, exercise more being maybe the most dominant theme I've heard through me going back to when I was an officer in the Navy working with people struggling to meet the Navy's weight standards back in the eighties to even through my professional career. And it seems to me one of the things that the neuroscience of body fatness and eating has done is really unveil how these things are regulated. So it's not as chosen for us as height, but it's maybe not as plastic as we think either.

Can We Change Our Weight Set Point?

Dr. Stephan J. Guyenet: Yeah, that's right. And yeah, I think that's a good way to think about it. And the thing is that the amount of food that we eat is a very powerful lever, or let's say the number of calories that we eat is a very powerful lever that we have to change body fatness. But the problem is that changing the number of calories that we eat is not as easy as it may seem because of the fact that our calorie intake is not just regulated by conscious, rational brain regions. It's regulated by this whole interacting cluster of non-conscious brain regions that have their own agendas and that evolved under specific circumstances that were very different than the circumstances that we're in today.

And so we have parts of our brain that regulate body fatness in the same way that we have parts of our brain that regulate body temperature and blood pressure. And those brain regions are not under our conscious control. They're receiving inputs from our environment and from our physiology and they're generating outputs, and we can react to those things, but we can't directly control those things. And that's just one example. There are other brain systems that we can talk about as well that control our appetite. Like how hungry are you? Is that something that you chose for yourself or is that just the product of your physiology interacting with your neuroscience? I think it's pretty clearly the ladder. You can't just think your hunger away. And that's not to say we have no control, but the control is very indirect. So we can't just shut hunger on and off like a light switch. It's something that arises on its own and that goes away under certain circumstances like we eat food.

And so I think you said it well in saying that we do have some control. If somebody put a gun to my head and said, Don't eat that plate of food in front of you." Or, "Don't eat that bowl of ice cream," let's say, then I wouldn't eat it. But if there's not a gun to my head, then I probably am going to eat it if it's right in front of me and it looks delicious. And so there are these non-conscious brain systems that, let's say they strongly suggest what kind of eating behavior we should have. They're not dictating, but they're strongly suggesting what kind of eating behaviors we should engage in. And if you don't want to do what they say or what they're strongly suggesting, you're basically going to have a struggle on your hands. You're not going to be eating to hunger, you're not going to be satisfying your cravings, and you're basically going to be in a situation where your conscious, rational, so-called system two brain processes are battling your non-conscious instinctive system one brain processes indefinitely.

And that's a situation that's not very sustainable for most people. And it's a key reason why you see weight regain in weight loss trials. So people, they adopt a weight loss strategy like let's say a low fat diet or a calorie controlled diet or a low-carb diet, and usually they'll get maximum weight loss sometime around six months into the diet. Usually that maximum weight loss will not be as much as they hoped it would be. And then usually over the course of the next six months, they will regain some portion of the weight they had lost over the first six. And so by the time you look at them a year later, in the average program, the average weight loss program that's tested in rigorously in a randomized controlled trial, you're going to see usually people are maybe five to 15 pounds down, which is, it's not nothing, but it's not usually what people are setting out to lose.

And so I think there's this really big disconnect between, first of all, what is theoretically possible over that period of time. I mean, over a year, in theory, you could lose a ton of weight. A person with obesity could lose probably most of their excess fat mass over a year, depending on how fat they are and how aggressive they want to go at it, in theory. And then also you have this mismatch between what's possible in theory and what's possible in practice that's being accounted for by the activity of these non-conscious brain systems.

And then you have the difference between the impression that you might get from social media and from the examples that you might see promoted by a particular weight loss program, they find the most successful person and they amplify the story of that person, but that person's not representative. They're choosing the people who did the best on the program, not the average results. So when we look at randomized controlled trials where we can really look at averages, then what you're seeing is the real picture of what is closer to what the average results that the average person would actually get.

So there's all these disconnects between people's expectations and their preferences and what is theoretically possible and what is practically possible that not only leads to suboptimal results, but leads to a lot of frustration.

Dr. Greg Kelly: Well, and one of the things I think that you did a great job in your book at making clear is that so often I would've heard in practice, "Oh, willpower," right? A doctor will tell me, "Oh, my patient's not doing my diet hard enough or strict enough," or somehow they're failing. But what you point out in your book is, I think you called it the starvation response. I tend to think of the TV show Survivor in the early years when they would be calorie deprived, they wouldn't have enough food. So you start to see this slew of different behaviors pop out, which on that TV show would be they'd be a bit more lethargic. They'd want to talk about food all the time. Now of course, they were losing weight, but their brain would be fixated on food compared to what they would've been like in a non, I guess, Survivor scenario.

And I think in your book, you know, talked about the Minnesota starvation experiment and some other research that's really gone into how neuroscientists now understand this, I guess, starvation response kicking in when we're trying to live below the amount of weight or body fat that our brain thinks is right for it. So could you talk a bit more about the starvation response that would be seen in some of these studies?

Dr. Stephan J. Guyenet: Yeah, and I want to start by just taking a kind of high level view of the just use willpower perspective versus the, it's not about willpower perspective. And I think it's obvious that willpower does play some kind of role. I think if you have no discipline at all, it's going to be hard to do anything directly or indirectly to regulate your weight. So it's not like willpower is totally irrelevant, but I've always thought it was kind of funny when people assume that it's all about willpower. All you have to do is generate willpower and not eat the excess calories that you're currently eating. And I'm like, it's almost like people assume that the average person can just generate infinite willpower indefinitely every day forever. It's like, where is all this willpower going to come from people? We're not superhuman. We have the willpower that we have that's determined by our genes and environment. And so even the amount of willpower that we have is not completely under our conscious control.

And so I think it becomes pretty nuanced and to just say, "Just use willpower." Well, what's your strategy for giving people the willpower to resist the starvation response for years, potentially for the rest of their lives as they continue to eat less food than their body is telling them to? What's your strategy for making all of that willpower? It's just strange that people assume that others have this infinite source of willpower. It's not realistic.

So the starvation response, essentially what we see is that the brain detects when body fat has declined from the brain's preferred level of body fat. So the brain has a sort of level or range of body fat that it prefers, I call that a set point in my book. Other people might call it by different names. But it's basically the amount of fat, similar to how your body regulates temperature around a really narrow range, well, your brain regulates body fatness around a certain range that it prefers. And when a person gains fat, like develops overweight, develops obesity, their set point is actually elevated. So whatever their kind of comfortable weight is, if they're not trying to gain or lose, that's around where their set point is going to be.

So a person with obesity typically is at their set point. And when they start to lose weight, whether that person has obesity or not, their brain is going to detect that as a threat. So you start losing fat mass, the level of the hormone leptin in your bloodstream declines and your brain detects that, particularly your hypothalamus directly and indirectly gets the message that your fat is going away. And because of the conditions that we evolved in, it responds very vigorously to that. So it doesn't want your fat to go away. Same way as if your body temperature started to decline, your brain would start to engage behavioral and physiological responses to bring your body temperature back up. So it's going to engage around fat, it's going to engage shivering, it's going to do vasoconstriction, it's going to make you want to put on a sweater, go inside, drink a hot beverage, et cetera. And that system works really well at regulating your core body temperature.

And so similarly, when you start to lose fat, your brain, particularly your hypothalamus, engages a suite of physiological and behavioral responses to regain that lost fat. And so you feel more hungry, you're more interested in seductive calorie dense foods, your attention is biased toward food items rather than non-food items. If you lose enough weight, your metabolic rate will start to slow. So you're burning fewer calories even per unit lean mass. So your metabolic rate kind of slows down. And so basically your brain is trying to stop calories from leaving your body and increase the rate of calories coming into your body and take all that extra and put it in your fat. And that continues until you've regained your lost fat mass and then your brain is kind of satisfied and you're fine.

And so that's why you see, if you take a group of people with obesity and you have them lose 10% of their body weight, and then... let's say you have a group of people with obesity, they've lost 10% of their body weight, and then you have another group of people who are at their comfortable weight, but they're at the weight, the same weight as the first group after their loss. So same starting weight, but one group has lost weight to get there, the other group hasn't. What you're going to see is that the first group is going to regain weight a lot faster than the second group gains weight. So they're going to kind of rebound as a function of that starvation response, pushing their food up. So that's just another form of homeostatic regulation that the body does. There are many different kinds of homeostatic regulation. Many of them are regulated by the brain. Body fat is just one of those systems that works like that.

Dr. Greg Kelly: I think of it as being very similar to sleep. If we're sleep-deprived, then a fairly natural thing is to feel more tired, to feel sleepy. But there'll be all kinds of other bio-behavioral changes that our brain's doing to adapt to that. And I think that's something that's, other than experts like you in your book, that's often missed, that I know it'd be what I look for. So let's say person A changed their diet and they lost weight, but the starvation response didn't kick in. It would seem like, okay, what they did, their brain is now readjusting their set point. Where person B, they maybe decided to continue eating the same foods, eat less of them, they've lost the same amount of weight, and now they're hungry. They feel like they have no energy. The metabolism slowed. So in that sense, it's not just looking at the weight change, it's looking at the response the brain kicked in because of the weight loss.

Dr. Stephan J. Guyenet: Yeah, that's right. And this is an area where we really need more information on. Are there ways via diet or otherwise to change the set point and how does that affect people's ability to lose weight and their likelihood to regain weight? I think there's a little bit of direct evidence and a fair amount of indirect evidence that we actually can change the set point, that we can lower it that is, to make weight loss and maintenance easier. But I think we don't have great evidence to support that right now.

Dr. Greg Kelly: Yeah, it seemed like most of what you point out in the book has to do with animals, but I know it was one of the examples you mentioned was, I think it was mice or rats, but changing their diet drastically seemed to affect the set point that they seemed most comfortable at. And I believe it was maybe a few April Fool's days ago, you announced you were going to do a bland diet cookbook. And that's part of the idea behind it is, and I want to talk a bit more about dopamine and flavor learning, but how rewarding a diet is in animals seems to make a big impact on set points.

Dr. Stephan J. Guyenet: Yeah, that's right. There is some evidence in both humans and animals, but it's stronger in animals, that if you change basically how appealing the diet is, how seductive it is, you can change their set point. So the weight around which their brain wants to regulate, and you can increase the set point and you can decrease the set point in animals. And there's some evidence in humans that you can do that too, but again, it's not as strong.

Dr. Greg Kelly: I know for me, going way back, when I was college and before someone always put food in front of me and whatever was there I ate, and just as much as I was hungry enough to eat at the time. And had a pretty big appetite for being a fairly small person and was, through most of my early college years, fairly resistant to gaining weight. And then towards the end of college years, not as much. And going into the Navy was going to be the first time I had to feed myself basically. So I asked a friend that was a gym rat, what I should do, he gave me a book that was popular in '84 called Eat to Win, I believe, by Alison Haas, but it was the high complex carbohydrate, low fat was what was popular then. And that became my simple heuristic. If something had a lot of fat in it and something else, then that was my deciding point.

But one thing I do remember from that time period was that fairly quickly after I left college, no longer was doing the super late night eating, committed to doing more exercise, changed what I ate, my body pretty effortlessly dropped about 25 pounds that I never struggled to put back on. But it wasn't just one thing, it was the whole context of my life shifted and it seemed like my set point shifted with that.

Dr. Stephan J. Guyenet: Yeah, that makes a lot of sense. And that would be a situation where I would say we have indirect evidence that your set point changed. And the reason is that you weren't counting your calories. Well, I'm assuming that's true. Is that true?

Dr. Greg Kelly: That would be true, yes.

Dr. Stephan J. Guyenet: Okay.

Dr. Greg Kelly: I've never counted calories.

Dr. Stephan J. Guyenet: Okay, you weren't counting your calories, you were making qualitative changes to your diet and to your lifestyle and your calorie intake and body weight naturally dropped without you having to deliberately restrict. And so to me, that provides indirect evidence that the set point has changed and you're regulating around a lower level. And that's what you see in a lot of these diet trials. There are diet trials where people are setting calorie goals and trying to restrict calories, but there are a lot of diet trials where there's no calorie goal at all. All they're doing is doing qualitative changes to the diet.

And the low-carb diet is a classic example of this. Low-carb diet. People typically are not counting calories, they're not deliberately restricting calories. And the diet often is pretty calorie dense. So often a lot of the foods people are eating are higher in calorie density because they're higher in fat. Not necessarily, but I think typically that would be the case. But yet nevertheless, people spontaneously, their calorie intake declines and their body weight declines. So they're not trying to restrict calories that's just happening as a natural result of the qualitative change in their diet. And we can talk more about why I think that happens, but I think that that is a scenario where I would say we have indirect evidence that the set point has changed.

And we see the same thing, you can look at diet trials where they increase protein content of the diet under really strict controlled conditions. People's calorie intake drops by hundreds of calories just spontaneously when you increase the protein content of the diet. And the trials that I'm thinking of, some people, their kind of immediate objection would be, well, if carbs are the reason they're overeating and the protein's replacing carbs, then that would be why. But in these trials, they were replacing fat with the protein, and so the carb content is not changing. What's changing is the fat to protein ratio. And you can see it works the same way with carbs and with fat, basically, if you replace either one with protein, people's calorie intake spontaneously declines. And anything you do to go away from a diet that's rich in both carbohydrate and fat. So if you reduce fat or you reduce carbohydrate, even if you're increasing the other macronutrient proportionally, total, total calorie intake tends to spontaneously drop and body weight tends to spontaneously drop.

And there are lifestyle factors too. It's not necessarily all just about diet, but there are these things that you can change in your diet that cause spontaneous decline in calorie intake and body fatness. And to me, we don't have the neuroscience in humans to say that this is because of a change in set point. So I want to caveat with that, but I would say this provides some indirect evidence that there is a change in set point when you see these changes occurring without a deliberate restriction of calories.

Dr. Greg Kelly: And I think I like your use of the word spontaneous. So would this be fair to say that if someone's struggling with or dissatisfied with the amount of weight and eating a certain diet, eating less of the same foods is maybe more likely to cause that starvation response? But qualitatively shifting the diet in a way that maybe now you effortlessly lose weight would be an indirect idea of, oh, these qualitative changes made an impact on set point, where simply trying to eat less of what you're already eating is maybe less likely to work?

Dr. Stephan J. Guyenet: Yeah. I tend to think that that is the way that has a higher likelihood of success. And I just want to be clear that I'm not presenting this as the weight loss silver bullet, lose every last gram of excess fat. So weight loss is really challenging. So I'm not trying to say that this is the ultimate solution, but I do tend to think that for most people it's going to be easier if they are working with these brain circuits and recruiting those brain circuits to support them rather than engaging in an ongoing struggle with these brain circuits.

The Role of Dopamine in Flavor Learning

Dr. Greg Kelly: Well great, this is a great segue now into dopamine, which I know our community loves to hear about dopamine, and it was one of the star neurotransmitters in your books. Can you tell us a bit about the role dopamine has in food learning? Or would conditioned flavor learning be a right term to use? Or is there one neuroscientists prefer?

Dr. Stephan J. Guyenet: Yeah, I mean, condition conditioned flavor preferences or conditioned flavor learning is kind of a facet of it. So I'm going to give it a little more of a big picture view, if that's all right? So essentially we have this system in our brain that helps us to learn how to behave based on experience. And there are different ways our brains do this, but one of the really simple ways is reinforcement learning. And the way the system works is really simple, when something good happens, your brain just makes it more likely that the behaviors that you did right before that good thing happened are going to recur. So that's reinforcement is your brain says, "Oh, you just got a whole bunch of carbs and salt and fat in your belly. That's a good thing. And so we're going to increase the likelihood and the intensity of the behaviors that you did right before that," which might involve going to the store and buying cookies or might involve baking cookies or might involve visiting your grandma who makes cookies, whatever the scenario was that got you those cookies.

So this is a system that evolved over hundreds of millions of years where you have animals that are trying to find food in their natural environment, and they're engaging in certain behaviors to get there, and successful behaviors are rewarded by the dopamine system and increase in intensity and frequency after that when the right cues are encountered.

So to get a little bit more specific, if we, let's say that you're a little kid, let's say you're three years old and you've never had pizza before and you're about to have pizza for the first time. And so you sit down at the table and you start eating this pizza and that starts hitting receptors in your digestive tract. It hits receptors in your nose, in your mouth as you swallow. There's information being collected in your stomach about the volume of food that you've eaten. There's information in your small intestine being collected about the composition of what you ate, amount of carbohydrate, the amount of fat, the amount of protein, the amount of salt, and the amount of glutamate, which is like that meaty umami flavor.

And all that information gets sent up to your brain. And your brain is hardwired to recognize certain chemical and physical properties of food as good. And those are the ones that your brain is hardwired to release dopamine when you consume. And so this is what's called an unconditioned stimulus. You don't have to learn that fat is good. You don't have to learn that sugar is good. Your brain is pre-wired to value the acquisition of those substances.

And so all that stuff hits your digestive tract. It's hitting all these receptors, these chemical receptors all throughout, and that's sending a signal up to your brain and that releases dopamine. So you have dopamine getting released, especially by the ventral tegmental area, and to some extent the substantia nigra. Those are going into the striatum, especially the ventral striatum, but also the dorsal striatum, that dopamine is getting released there and in associated brain regions in the cortex. And that's basically saying, whoa, something good happened here. Something really cool just happened. And that dopamine signal is reinforcing, it's stamping in all the cues that you experienced. So the smell of the pizza, the texture that you detected in your mouth, the taste of it, the context you were in, the people you were with, the location you were in, all of the sensory cues that you were experiencing while you were consuming that get stamped in by that dopamine. So that's the reinforcement learning aspect.

And so the next time you experience those same cues, so let's say it's a week later and you smell the smell of pizza, your brain recognizes that smell. Well, that's a cue that's associated with all of these desirable nutrients, that's a cue that predicts all of these desirable nutrients. So bam, it's going to activate that behavioral program again of seeking and consuming that pizza. So your subjective experience is going to be that you experience a motivational state, you experience, you feel motivated, you feel a craving to eat that pizza, and probably to eat a lot of it, because that's got a high concentration of all those nutrients that your brain inherently values. And so you're going to want to really chow down on that to get all these valuable nutrients that would've increased the survival and reproduction potential of your distant ancestors.

And so that's the way that these sensory cues get reinforced. Eventually, the dopamine release gets attached to all those sensory cues. So as soon as you smell the smell or see the box or whatever, your dopamine's spiking, your motivation is going, you're feeling that craving. So you don't even have to eat the food anymore to get that motivational surge.

And that's how we acquire flavors. So we started off this question you were asking me about flavor learning or flavor conditioning. And so if you have a flavor that starts off as a neutral flavor, maybe the first time you taste tomato sauce on a pizza, you don't like it, you don't dislike it, it's just take it or leave it. But once it's been associated with the salt and the fat and the carbohydrate and the protein in a really calorie dense form over and over again, you're going to acquire a taste for that tomato sauce. So that is a conditioned stimulus at that point, meaning that it's not something that's hardwired into your brain, it's something that you have learned as a result of pairing flavors and nutrients.

And so that's how we learn to like bitter beer and bitter coffee. Coffee of course, contains a habit-forming drug that acts on the dopamine system, also we put sugar and fat into it typically. That's how we acquire a taste for strong cheeses, for bitter beer, for all of the kind of culture specific foods that one culture likes and another culture doesn't. Meanwhile, everybody likes fat and salt and carbs, right? So that's how it works.

Dr. Greg Kelly: My understanding is that a big part of food science, so companies making foods that they want us to consume more of, buying more of often, is taking advantage of flavor learning and high palatability, combining things like salt, sugar, fat, intense flavors so that we'd have a big flavor learning experience when we eat that food. Would that be somewhat accurate? Or [inaudible 00:38:34]?

Dr. Stephan J. Guyenet: Oh, absolutely. Absolutely. And the thing is, I don't know how much companies deliberately optimize for this. I know if are some companies that have FMRI machines so they can see brain activity when people are eating their food? So there probably is some awareness at a few major food corporations, but I think mostly what happens is we have an intuitive sense of it. We know what we like and we know what we want to eat over and over again instead of just eating it once and never buying it again. And people know how to design foods with certain... your grandma knew how to make cookies that were really good and that you liked, right? There's an intuitive sense of what is seductive to the human palette. And so I don't think you necessarily have to have the neuroscience perspective if you're a food corporation to design foods that are appealing.

And I also think even if we didn't have that intuition, even if we knew nothing, you would still end up just by, you could call it natural selection in the consumer marketplace, you would still end up where the foods that were successful and that stayed on the shelves were the ones that are the most rewarding dopaminergically, because what does dopamine do? It reinforces purchase and consumption behavior of these foods. And so the ones that are selling well are the ones that are really good at stimulating your dopamine. And of course, dopamine's not the only thing that determines whether we buy a food or not, but it's a big one. And so you're not going to have foods on the shelf that are not seductive to the dopamine system. Those are just not going to survive in a competitive capitalist economy. So there's this weeding out process that is happening in the grocery stores where, for a food to be successful on the shelf, it has to stimulate the dopamine system really effectively.

What an fMRI Experience Reveals About Food Cravings

Dr. Greg Kelly: Well, you had mentioned the FMRI, it was one of my favorite stories in your book, when you talk about biking over to have your brain looked at. Could you maybe share a little bit of that experience and the take home from it for our audience?

Dr. Stephan J. Guyenet: Yeah, absolutely. So I have a colleague whose name is Ellen Scher and her research team, they do FMRI, functional magnetic resonance imaging, which is where they are, I don't need to get into the details, but they're measuring brain activity in real time. So instead of just a anatomical scan like you would typically get in an MRI where you just see what the tissue looks like, in this case, you're actually looking at brain activity. And it's looking at blood flow basically, which is a measure of brain activity. And so you're sitting in an FMRI machine, your head is kind of contained in this thing to keep it still, and you are looking at images.

And so you can show people images to stimulate different activity in their brain and study how that interaction works. And so in this case, what Ellen's team was doing and the protocol that they used for me was they were showing people images of either highly caloric, very seductive foods, like junk food fries, hamburgers, chocolate, stuff like that, lower calorie, less seductive foods like vegetables and fruits, and then non-food items. So the non-food items are basically to weed out what brain activity is happening when you're just looking at an image that's unrelated to the actual fact that this is food.

And so they show people these different images and they see how it affects people's brain activity in areas related to eating drive and other things in people who either have not eaten or people who have eaten. And that tells you something about the impact of satiety on these type of motivational eating drive related brain regions. So that that's kind of the general idea of what they were studying at that time.

And so I go in, I hadn't eaten anything. It was, I think early afternoon I hadn't had breakfast, hadn't had lunch, and I had ridden my bike for an hour to get to the medical center. And I thought that they were going to do a scan then give me food and then do another scan, but in fact, we just did one scan. And so that's why I didn't eat because I thought I was going to eat something there.

And what they found is that when I was looking at the high calorie food items, these motivation related brain regions, I was just telling you about, the VTA, ventral tegmental area, and the ventral striatum, which is that dopamine circuit that we were talking about, was just going crazy when I was looking at those foods. Specifically the high calorie foods. The low calorie foods, my brain barely had any response. It was like I was not interested in chowing down on some broccoli when I was starving, would be the interpretation there. And then there was also some activity in the orbit of frontal cortex, which is involved in integrating all of this information about your body's energy status and many other things and helping you to make a decision about what to do next. And my brain at that moment, presumably was telling me thinking about eating some food.

But one interesting thing that I didn't discuss in the book actually is that I was looking at those high calorie foods and I actually wasn't experiencing hunger at that time. So I wasn't consciously aware of feeling like, oh, I could totally chow down on this pizza right now. And the reason is that I was getting an uncomfortable side effect from the F MRIs, getting something called peripheral nerve stimulation. And that's something where the MRI is such a powerful magnet, it'll actually trigger some of your motor nerves. And so I had this nerve in my abs that was just firing every time the FMRI was going on, and it was really uncomfortable. I didn't know what it was. And so it was kind of freaking me out. And nevertheless, despite the fact that I was kind of freaked out and wasn't actually feeling hungry, on some level, on some deep primordial level, my brain was still totally drooling over that food I was looking at.

And so I think that's really a really interesting example of how these brain circuits, when you're in an energy depleted state especially, are really, really interested in calorie dense foods. But if there's another stimulus that's more important at the time like perception of danger, then that's not necessarily going to trickle up to your conscious perception. It might not be until after the danger has passed that you experience that craving.

Dr. Greg Kelly: I think to me, one of the takeaways was again, just below that level of our awareness, how powerful the brain was acting to correct an energy imbalance, which yours was short term because it was just one or two missed meals and some exercise. But as you mentioned, if someone's been calorie restricted to lose a lot of weight, it might be reasonable to think their brain's going to be in a state like that much of the time.

Dr. Stephan J. Guyenet: Yeah, that's right. And my brain was... those circuits were really activated. That was one of the strongest responses they had ever seen in my substantia nigra and VTA. So the exercise and the fasting that I did, my brain was really fired up on that non-conscious food seeking level.

Tips to Outsmart the Hungry Brain

Dr. Greg Kelly: One of the things I wanted to get to, and now is I think a good time would be, since your book came out, because it's a few years old at this point, has there been any new research that's really grabbed your eye or any new research that might have said, oh, this really confirmed something that I was less sure about when I wrote the book?

Dr. Stephan J. Guyenet: Yeah, I'll give you two examples. I'm going to do a high level answer to this first and then I'm going to give you two examples, one that confirmed something in the book and one that has challenged something in the book. So the big picture I want to say is that there's been a lot of research on this that has happened since I published my book. But also even aside from that, being the director of Red Pen Reviews and kind of bathing in issues of information quality and how do you write the best book you can possibly write and how do you judge what's high information quality and what's low? I've just gotten better at interpreting evidence over time. And so I think even the evidence I had at the time, I think I could do a better job of interpreting now. But in addition, the research has moved on over time. And so there are some updates.

So the one that I'll say that has challenged something in the book is there's been some research, primarily from this researcher named Herman Pontzer who is a-

Dr. Greg Kelly: I've read his book, Burn.

Dr. Stephan J. Guyenet: ... Okay, yeah, it's a great book. It's a great book.

Dr. Greg Kelly: I would agree, an excellent book. Yep.

Dr. Stephan J. Guyenet: Yeah. He's a physiologist and anthropologist, I think that would be a good description of what he is. And he has this hypothesis that, let me see how I can describe it in a concise way. I think everybody always kind of assumed that when you exercise, your calorie expenditure goes up, and obviously it does while you're exercising. We get hot, we get sweaty, your body's burning more energy. And people always assumed that that extra energy that you burn when you're exercising just kind of gets added on top of the total that your body is burning each day. And so if your body at rest burns 2000 calories and you do 500 calories of exercise, you're going to burn 2,500 a day. And that's kind of what everybody always just assumed. And all the energy expenditure calculators pretty much ever have assumed that. And basically he's saying, no, I don't think that's right. What the body does over long periods of time, if you're exercising regularly, your body cuts back on your energy expenditure from other stuff in order to constrain your total energy expenditure for the day.

So in that situation, if you're consistently exercising, burning 500 calories from exercise a day every day for let's say a year, two years, you're not going to be burning 2,500 calories anymore. You're going to be burning like 2100 or maybe 2150, whereas your previous was 2000. If you weren't exercising, you're at 2000. So it's not that your body is getting more efficient in exercise itself, it's that your body's getting more efficient about all the other stuff. Your basal metabolic rate is declining to keep your total expenditure under control. And so he has this hypothesis and he's collected some data that support it. I think there have been some, I think, effective critiques of it from Javier Gonzalez for example, had a really great paper recently that was critiquing Herman Pontzer's model. So it's not completely airtight, but there's some pretty compelling data for it. And I think based on what I've seen, it's probably at least partially correct, and it might even be entirely correct.

So basically this assumption that we had, this simple addition, this simple arithmetic that we used to do for total energy expend is may not be correct. And that was one of the assumptions in my book that I made in one of the earlier chapters is that, you do more physical activity, you burn 500 calories a day in physical activity and that's an important change to your overall energy balance sheet. But in fact, that may not be true. It may be the case that your exercise just is not as powerful of a lever as we thought over your body fatness and your overall energy balance, and that in fact it really is more about how much you eat.

And I think that's kind of consistent with the fact that if you look at randomized trials of diet interventions for weight loss versus exercise interventions, the diet interventions tend to be a lot more effective. So you do get some weight loss with exercise interventions, but the effect size is smaller. It's smaller than you would predict if the additive model of energy expenditure were correct. And it's a lot smaller than what you get from dietary changes. So I think that's one update that I think is pretty important. And if that's true, it suggests the diet piece is a lot more important for weight control than the exercise piece, at least for weight loss.

And then the second thing where research has just confirmed and fleshed out something that the book has talked about is I talk about the way that the brain gets the information from the digestive tract that allows it to measure the nutrient content of what you ate to determine how much dopamine to release. So somehow that signal has to get from your gut to your brain for your brain to know how much dopamine to release in response to that fat and carbohydrate and salt, et cetera. And at the time I wrote my book, there was only speculation, well, there was more than speculation, but we didn't know how it got from the gut to the brain.

I'm a neuroscientist, so my bias was that it was conducted by nerves. That would make the most sense because the information content that you can deliver from nerves is just much richer than what you can deliver from hormones. Hormones are a really crude communication method, whereas nerves are a very sophisticated communication method physiologically. And so that was my bias and that was confirmed. I didn't say that in the book by the way, but that was confirmed. And essentially what we now know is that there are specialized cells in the lining of the digestive tract, especially the small intestine, that detect nutrients in food. They detect the fat and the carbs and other nutrients. And those cells, they're called neuropod.

Dr. Greg Kelly: The gastropod? Okay, yeah.

Dr. Stephan J. Guyenet: Neuropod, yeah. Neuropod cells. I think that's right, isn't it neuropod? I think that's right. Anyway, they're directly connected to the nervous system. So they are directly connected both to the intestinal lumen, the inside of your digestive tract, and to a neuron. And so they detect those compounds in your digestive tract and they directly stimulate those nerve terminals. And that then takes its winding path up to your dopamine centers that releases dopamine in the brain.

And those neural pathways, if you stimulate them, are powerfully reinforcing. So that shows that this nutrient, gut-brain pathway is mediating a reinforcement signal that has a powerful impact over our motivations and our behaviors.

Dr. Greg Kelly: Yeah, I think it was when the research first was, those cells, I would use the term tasting, but tasting sugars that made it to that point. So wasn't just what we can taste in our mouth, it's what our gut brain access is tasting and responding to. So with that segue, we're starting to run shorter on time and I wanted to find out if there was any really suggestions that you would make for an audience member that's maybe been struggling with trying to lose weight. I'm not saying that they have to be UMAM studies, but just some things that, based off either indirect or animal, that you feel like this would be an experiment that might be worth running if the things you've been doing haven't worked to date?

Dr. Stephan J. Guyenet: Yeah, so as I said earlier, I think the strategy that I prefer is of trying to understand that we have these non-conscious brain systems that are influencing our motivations and our behavior. And instead of trying to fight those systems, try to understand what they are and work with them and even try to recruit them to support our weight management goals.

And so there are a number of things that I talk about in my book that you can do in that regard. But I think some of the simplest and most impactful ones, one is to control your food environment. So as we talked about this dopamine motivation system, it's triggered by sensory cues that predict the acquisition of certain nutrients. And so as a complicated way of saying if you're in your kitchen and there's chips on the counter, you're probably going to want to eat them really bad. And so don't have chips on the counter. But it goes beyond that to, you don't want to have the sight or smell of seductive food items in your personal environment if you can avoid it. So don't have things on the counter, don't have things that are easily accessible in the place where you spend most of your time, so outside of meal times at home and at work.

So that's one thing. Another thing related to that is you can create little effort barriers. Because a lot of times, you might be motivated to eat, maybe you're a little hungry, maybe you're a little bored, but you're not like starving. You might go start grazing because you're bored or a little hungry, but if you had to actually do real work to get that food, you probably wouldn't do it. And in fact, if you knew in the back of your head that you would have to do that work to get the food, you probably wouldn't even even think about it.

And so that's why I think the foods that you do have around, it's helpful to have little effort barriers built into them and have them be foods that are not especially seductive. So for example, whole oranges that you would have to peel if you wanted to eat them. So if you're actually really hungry, you can have an orange, you don't have to go starving. But if you're just a little hungry or you're bored, you're probably not going to peel an orange to eat it. Whereas you probably would open a bag of chips or grab a cookie or something like that. Or nuts in shell, unsalted nuts in shell. So by omitting the salt, you're reducing how seductive it is. And the shell is an effort barrier. And how long are you going to be sitting there cracking nuts and eating them? Probably not very long, unless you're actually genuinely hungry. So those are a couple of things around helping you naturally regulate your food intake.

And then another thing that I think is really helpful, we didn't talk a lot about satiety, but I think the satiety system in the brain is really impactful of our calorie intake. And essentially when you eat food, there are all these receptors in your gut that detect what you ate, the volume, the composition, et cetera, all the stuff we were talking about. Well, that information doesn't just go to your reward centers, it also goes to your satiety center. And essentially as you continue to take bites of food, you have this signal going up into your satiety center that's building up, building up, building up, and eventually your satiety center and your brainstem just says, okay, we've had enough. And then you lose your interest in continuing to eat food, it doesn't taste as good anymore, you don't have any more motivation to eat it, and you push the plate away and do something else.

We tend to intuitively think that that happens when our stomach fills up, like we sit down and eat till the stomach is full and then that's when we terminate our meal. But in fact, usually people are eating less than half of their stomach capacity at a particular meal. That feeling of fullness, of satiety, of loss of eating drive, that is brain activity. That's not your stomach filling up, that is your brain saying that you've had enough.

And so how do you get your brain there? How do you get your brain to that point where it's had enough? Well, it turns out that it's, that's not just determined by your calorie intake, it's also determined by other things in your diet. And so you can achieve that point. You can get to the satiety, or satiation technically, while eating fewer calories. So you can still be satisfied with fewer calories. And there are studies that have measured how you do this and eat higher protein, higher fiber, lower calorie density, that's going to give you more satiety per unit calorie. Conversely, if you're eating low protein, high calorie density, low fiber and high palatability, you're going to require more calories to get to that place of feeling more full.

So in those two scenarios, you're, you're going to end up full either way, but you just will have consumed a lot more calories in one than the other. So basically the calorie dense, processed junk foods are the ones that have very low satiety per calorie, and the less processed, less refined foods, more like the whole grains and the fresh meats and the fresh fruits and the vegetables, the eggs, those are the kind of things that have properties that provide more satiety per calorie. And so I think that's two tips, one related to controlling your food environment and one related to the types of foods that you're eating. And I think those two together can, I think, make a lot of headway with those two.

Dr. Greg Kelly: You mentioned the satiety index, and I think it's Dr. Holt's work back in the nineties on that. But I know I'm Irish American from Boston originally, so I feel like my ancestors learned how to eat potatoes over at least multiple generations. And I think before encountering work, I was familiar with the glycemic index, and potatoes typically not being great on that index, but on the satiety index, boiled potatoes scored really high, because again, what you point out, they're relatively low palatability, they're a fairly bland food, there's a lot of water and other things in them, and they strongly stimulate our satiety center in the brain that we've had enough without having super high amounts of calories. Now, if we slice them really thin, fry them in oil, put salt, flavoring, all kinds of other things to make them yummy, not so much.

Dr. Stephan J. Guyenet: Yeah, a different story.

Dr. Greg Kelly: For me, it's understanding that context that if foods have been engineered to be yummy and they taste yummy to us, then probably they're going to be not satisfying to that satiety part of our brain. Where if we can, I mentioned your April fool's joke about the bland diet cookbook, if we can do things to just, not make food non-enjoyable, but to just eat simpler foods, that might be a solution for many of us to get incrementally better body fat results over time.

Dr. Stephan J. Guyenet: Yeah, I think that's helpful. And simple food is what our distant ancestors ate. If you look at what hunter-gatherers eat, it's incredibly simple. Most of these cultures didn't have salt, they didn't have any kind of flavorings, or very few, and none that they used on a regular basis. They didn't usually have added fat or added sugars. They were just pulling foods out of the ground or pulling fruits off plants or killing animals and eating the meat cooked, or in some cases, for example, the fruit, raw. So really minimal processing. Cooking was really the main processing method. And I think that was the context that the human brain did a lot of its evolving in. The human brain didn't evolve to eat these foods that are just maxed out on calorie density and palatability and seductiveness. And so I think it just overstimulates us and we lose control.

Dr. Greg Kelly: Well, and the last thing I wanted just to mention before we wrap things up is I know I follow you on Twitter, and I think fairly recently you had put something talking about this condition flavor preference. And I think the suggestion was we might do a lot of that when we're younger, first learning about food, but obviously that's somewhat speculative. But I know the way it's worked for me at one point, traditional diet, Western diet, and then the high complex carb, that changed what I ate. So my brain learned about different foods. I became a vegetarian for six years. I had never eaten a whole bunch of things that then I was forced to try.

And what it's always seemed like for my brain when it encounters a new food that it hasn't had before, and typically these are simple foods, but persimmons would be an example from maybe five, six years back, I'd never had a persimmon. Pick some up at the farmer's market and for the next four or five weeks, my brain just could not get enough. Constantly like, "You want more persimmons." It seemed like it was dedicated to really learning about that food. And once it had learned it, put it in its memory bank, now if I get a craving for a persimmon, it feels like, oh, my brain learned about that. There's something in that flavor pairing that it really wants, let me go get it, a persimmon. My sense is that if we were more, I guess, conscious of flavor learning, that might actually also get us a long way to almost developing a richer language around how our brain regulates fatness and appetite and food intake.

Dr. Stephan J. Guyenet: And the scenario you describe, I don't know about it, I haven't heard of that before. But I will say that a fruit has sugar and sugar is an unconditioned stimulus, meaning that the brain instinctively recognizes it as desirable. And so there's not necessarily a lot of learning that has to happen around food that is high in sugar, like candy. Kids tend to candy the first time, they don't have to learn to candy. And probably that's because fruit and honey were sources of sweetness in the ancestral environment and those were both good things for our ancestors to get their hands on.

Dr. Greg Kelly: Wonderful. Well, thank you so much for being our guest on Collective Insights Podcast today. Is there any place where you can direct them to follow you? I know I follow you on Twitter, but are there other places that you think would be great places for our audience that wants to get more access to your work?

Dr. Stephan J. Guyenet: Yeah, I would say, first of all, check out Red Pen Reviews. RedPenReviews.org. We have free expert reviews of popular nutrition books and we have this really unique method that we use that gives really rigorous, but also really easy to understand evaluations of popular nutrition books. So check that out. On Twitter I'm @sguyenet, G-U-Y-E-N-E-T. And I have a website too, StephanGuyenet.com. I haven't been writing there a lot lately, but I do have some older articles posted still.

Dr. Greg Kelly: Well, thank you so much and again, thanks for being with us today on Collective Insights.

Dr. Stephan J. Guyenet: Okay, thanks for having me.