**Special announcement: you’ll notice we’re now providing a full transcript for each new episode of the show. Special thanks to Lindsey Gosling from our community for volunteering to do this. She’s my hero.
One of the most hotly debated subjects in the Paleo-sphere over the last several months has been the causes and treatment of obesity and overweight. Some claim that it’s simply a matter of “calories in, calories out”, and weight loss is just a question of “eating less, and exercising more”. Others claim that it’s all about macronutrients (fat, carbs & protein), and calories don’t make a difference at all.
Over the last two decades a more sophisticated theory of weight regulation has emerged that encompasses the seeming contradictions in the prevailing paradigms. This theory holds that the brain is the primary driver of weight gain and loss, and that environmental and genetic factors that influence this neurobiological system are what account for the alarming rise in obesity we’ve seen in the Western world since the early 80s.
2:57 Why it’s so hard to lose weight and keep it off
8:00 The truth about food reward, calories in vs. calories out, and “the metabolic advantage”
13:32 The Body Fat Setpoint making you “gain the all weight back”
21:06 Why leptin is the master fat hormone and what happens when you’re leptin resistant
26:05 The link between inflammation and obesity
31:00 Are modern foods engineered to make us fat?
49:48 The one thing any successful weight loss intervention must have
Links We Discuss:
- Stephan Guyenet: Author of The Whole Health Source Blog
- Stephan Guyenet: Body Fat Setpoint Series
- “The End of Overeating”
Full Text Transcript:
Steve Wright: Hi everyone, and welcome to the Revolution Health Radio Show. I’m Steve Wright from SCDlifestyle.com, and with me is Chris Kresser, health detective and creator of ChrisKresser.com. How are you doing, Chris?
Chris Kresser: I’m pretty good. I have to confess to being quite sleep deprived. Sylvie is usually a pretty good sleeper actually, but the last several nights she has been — I don’t know what’s happening, maybe a growth spurt or something, but she has just been squirrelling around the bed like a little monkey all night. Yeah, so if I start slurring my speech or just have large pauses or gaps, you’ll know what’s going on. How are you doing, Steve?
Steve Wright: We’ll be a pretty good tag team today then, because I’m working one-handed here, so I can basically only talk. I had shoulder surgery nine days ago, and everything went well. It appears to be good. I had a labrum tear, but I do have an arm in a sling for four weeks, so that kinda slows down life.
Chris Kresser: Oh, wow. Well, all right, so we’re injured and impaired, but we’re still here.
Steve Wright: That’s right. We can still talk!
Chris Kresser: Yeah, thank God for the radio show! So, let’s see, we have one announcement to make before we get started. Some people are already aware of this, I’m sure, but we now have full transcripts for all of the Revolution Health Radio and previous Healthy Skeptic podcasts in the works, which is really exciting. We loved you so much that we just decided that we were finally gonna do it, and we have a volunteer from the community, Lindsey, who is helping us with this on an ongoing basis, and we’re really grateful to her. She’s doing an awesome job, and so we’ve already put some of the transcripts up on the website, on the actual episode posts, and some of the older ones are in progress right now, and we’ll be adding them as we get them done. But in the future, I think we’re gonna be able to have the transcript up there right as the podcast or the radio show goes live, so that’s really exciting, and I hope you enjoy the transcripts, all of those who have been asking for them. I hope you enjoy it!
Steve Wright: Yeah, it will make things much easier to find with the Ctrl+F function.
Chris Kresser: Yeah, definitely.
Why is it so hard to lose weight and keep it off?
Chris Kresser: So, today I decided to review a study that was recently published by a friend of mine who I’m sure many of you know and a colleague, Stephan Guyenet, from Whole Health Source, one of my favorite blogs, and if you don’t know his work, I would highly recommend checking it out. I think it’s WholeHealthSource.blogspot.com. And Stephan published this paper with his mentor, Michael Schwartz. Both of them are at the University of Washington School of Medicine. And Stephan is an obesity researcher. He has spent his career studying the mechanisms involved in particularly the neurobiology of weight regulation, and he just published a paper called Regulation of Food Intake, Energy Balance, and Body Fat Mass: Implications for the Pathogenesis and Treatment of Obesity. And we’ll put a link to the paper in the show notes. Unfortunately the full text is not available for free, but the abstract is, and if you’re really interested you can cough up the, I think, 30 bucks or 35 bucks for the full text. I want to talk about it because Stephan’s been on the show twice already to discuss obesity and all the various factors involved in obesity, but I wanted to take another opportunity to revisit this because I think it’s much misunderstood. I think our understanding of it is continually evolving, and this paper, I thought, was the most concise and thorough synopsis of all of the various mechanisms that are supported in the scientific literature in terms of what causes weight gain and what might cause weight loss and keeping the weight off, because as everybody knows, losing weight is hard and keeping it off is even harder, and I want to explain in some detail why that is because, again, I think there is a lot of misunderstanding about that. So, we’re gonna spend quite a bit of time talking about this. It might even take the whole show. If we have a chance, we’ll answer some questions at the end, and I’m sure we’ll come back to this again. I’m not gonna get too far into what this means in terms of practical mechanisms because we’ll probably devote another show to that later, so this is just gonna be more of the background theory.
Steve Wright: Sounds good.
Chris Kresser: OK, shall we do it?
Steve Wright: Yeah, are you gonna start with a high-level overview or just dive right in?
Chris Kresser: Yeah, I’m gonna do a high-level overview, and so I’ll just give you kind of the basics of what we’re gonna be talking about, and then we’ll get into more detail about each point. The high-level overview, I’ve written about this on my blog as well, and as most of you know, I think, obesity is a multifactorial disease, and I think pretty much anybody who researches it seriously agrees with that. Anybody who says obesity is as simple as, you know, too much fat or too much carbohydrate or something like that is either misinformed or is intentionally misleading you. It’s far more complex than that, but I can boil it down into one simple phrase, which is modern lifestyle + genetic predisposition = obesity. And this is supported by the fact that obesity is virtually unheard of in populations that still follow their traditional diet and lifestyle. In modern hunter-gatherer societies, it is basically nonexistent. And then on the other hand, we know that there must be some genetic predisposition because not everyone who adopts a modern lifestyle becomes obese. I mean, surely we all have friends or family members that eat like crap and they’re still really lean, so there are obviously some genetic and epigenetic factors, as well.
Steve Wright: And lifestyle is food, stress, environment, everything?
Chris Kresser: Yeah, exactly, so everything from the food we eat to our — I mean, actually it starts even before that. It starts with our mother’s diet while she was pregnant with us, and it’s our gut flora particularly at the time of birth, whether we were breastfed. So, that’s maybe kind of depressing news for some people because we obviously didn’t have any control over that, but it turns out that those things can have a very significant impact on our risk for obesity as we get older.
The truth about food reward, calories in vs. calories out, and “the metabolic advantage”
Chris Kresser: One thing I want to talk about right up front is this whole — many of you who follow the Paleo blogs and are involved in this kind of thing have been aware of this debate that has been going on about food reward and calories in / calories out vs. the metabolic advantage or the idea that carbohydrates in particular predispose people to weight gain. You know, on one end of the spectrum you have people say that calories don’t matter at all; it’s more a matter of carbohydrate density and the type of carbohydrates that you eat, and if you eat a low-carb diet, for example, you can eat as many calories as you want and you won’t gain weight. And then you have on the other end of the spectrum people that say it’s all about calories, and as long as you’re in a negative energy balance, meaning as long as you expend more calories than you eat, then you will lose weight, and if you have an energy balance where you eat and expend about the same amount of calories, then you’ll maintain your weight. That’s a little bit of a false dichotomy, and I’ll explain why in a second, but I just want to say for the record that I think that calories do matter, and I think the research definitely supports the idea that calories matter. If you look at per capital energy intake — there’s actually a great graph in this study — in the U.S. it has increased about 20% since 1980, and that increase in energy intake or food intake over that period has closely paralleled the rapid rise we’ve seen over this past 30 years in obesity. I think where people get confused about this is that they mistake the idea that calories matter with the idea that eating less and exercising more is effective weight loss advice; and it’s not. And, you know, I absolutely agree with that. That’s been a monumental failure. The idea that you can just tell somebody to eat less and exercise more to lose weight is ridiculous and doesn’t work in the vast majority of cases, and we’re gonna talk a lot about why that is in the show today. But that doesn’t mean that calories aren’t a factor and that some interventions that reduce caloric intake wouldn’t contribute to long-term weight loss. This will be more clear as we get into it. I’m already kind of ignoring my own top-line review thing here.
Steve Wright: Hey, Chris, what was the 20%? Was that 300 extra calories a day or 400?
Chris Kresser: I don’t know the exact number, actually. Let me look here. I don’t know the exact number. I’d have to look it up. I just the percentage.
Steve Wright: OK.
Chris Kresser: So, another thing that we’re gonna focus on here is that over the last 20 years or so, research has shown that food intake and body fat regulation are primarily orchestrated by the brain. And of course, the brain gets input from another of other body systems, but it turns out that the hypothalamus in particular, and other regions of the brain play a really essential role in regulating weight and body fat mass and that obesity involves the biological defense of an elevated body fat mass, or another way of putting that is an increased setpoint, and we’ll talk more about this. And the increase in the setpoint, in turn, is mediated by interactions between the hedonic or pleasure/reward-seeking system and the homeostatic or energy-regulating system. And these, in turn, are influenced by inflammation, both peripherally, like in the gut and other parts of the body, and then in the brain, by leptin resistance and by other mechanisms that impair the function of the hypothalamus or those other parts of the brain that are involved in regulating weight. So, that’s the birds-eye view of what we’re gonna talk about, and it unfortunately gets a little bit complex in certain areas, so bear with me, and I hope it’s not overwhelming in those parts, but since we do have a transcript, you can go back and read it if it gets to be too much. So, all clear, Steve? Shall we go on?
Steve Wright: Yeah, I think one more time really fast do that crescendo of the various parts.
Chris Kresser: Well, basically obesity = modern lifestyle + genetic predisposition, and one of the ways that that is mediated, and the primary focus that we’re gonna talk about today, is the interaction between the hedonic and the homeostatic weight regulation mechanisms, and those are governed primarily by the brain. So, that’s kind of the gist of what we’re gonna get to today.
Steve Wright: OK, and then a bunch of things, like inflammation, affect the brain.
Chris Kresser: Yeah.
Steve Wright: Gotcha. Cool.
The Body Fat Setpoint making you “gain all the weight back”
Chris Kresser: OK, so let’s talk about the body fat setpoint. I mean, I don’t know if anyone has thought about this, but if you’ve wondered how most lean people stay the exact same weight or within a couple of pounds for years or maybe their whole life without counting calories or weighing what they eat, it’s actually a pretty remarkable system if you think about it. I mean, if it is true that the amount of calories you take in and the amount of calories you expend is what determines your weight, then it’s a pretty exquisitely regulated system to be able to maintain a range of weight within this 1 or 2 pounds without the person even thinking about it at all. So, this happens because survival in a natural environment is threatened by either too little or too much fat. If we have too little fat, we can’t survive periods of food scarcity and we starve; and if we have too much fat and we become obese, then we aren’t as fit to hunt and gather food and evade predators and survive. So, the body has a system for maintaining a level of fat that’s appropriate for the human ecological niche, and this is called the energy homeostasis system or the homeostatic regulation of weight, and it’s this system that’s one of the main reasons it’s so hard to keep weight off once you lose it, because the homeostatic system responds to any reduction in fat. Like if you lose 20 pounds, let’s say, this homeostatic system will increase hunger, it will decrease your resting energy expenditure, so even when you’re just sitting down the number of calories that you’ll burn will be lower, and it extract more calories from the food that you eat, so your metabolic efficiency goes up. So, it has all of these mechanisms that are basically working against you when you lose weight to get you back to that body fat setpoint or what it thinks is the ideal weight for you. On the other hand, if you were to gain 10 or 15 pounds, the body responds in the opposite way. It would decrease hunger, it would increase your resting energy expenditure, so you burn more calories just sitting there, and it would extract fewer calories from the food that you eat, and by doing that your weight would also fall back down to the setpoint. And so, a good analogy for this setpoint is a thermostat, and everyone knows how a thermostat works. Let’s say the thermostat is set at 70 degrees, and that’s the setpoint for the temperature in the house. And, you know, overnight the temperature drops down to 60 degrees, the heating system kicks in, and it brings it back up to 70 degrees. And then during the day the sun comes out, maybe the temperature goes up to 80 degrees, and then the air conditioner kicks in and brings it back down to 70 degrees. So, likewise, that’s how the body fat setpoint regulates our weight. That’s what happens in a normal-weight person, but what happens in obesity is that the thermostat, or the body fat setpoint, gets thrown off and the body defends a higher setpoint, which corresponds to a higher fat mass. And then when that person tries to lose weight, all of their efforts to reduce the fat mass are fought pretty strenuously by the body in the same way that a lean person maintains their normal weight. So, it’s an extremely effective system, and anyone who has tried to lose weight and keep it off knows exactly what I’m talking about. It’s really an up-hill battle, and that’s the depressing part about weight loss, and it’s probably why after all these years nobody has come up with the magic bullet. You know, weight loss is a billion dollar industry, it’s still a huge hot topic in the research literature, and really it still hasn’t been cracked, and that’s because we’re talking about some very old, very powerful, innate evolutionary mechanisms that are working against us, and any time we’re up against mechanisms like that, you know, that are mediated by our brain and not in our conscious control, it’s a challenge.
Steve Wright: So, when it comes to the setpoint, do we know anything about, like, how long it takes to slowly reset? Because there are a lot a people who do lose the weight. I’m not sure how many. There are people who lose the weight and keep it off, and then there are definitely plenty of people who lose the same amount of weight but then gain half of it back, so is it more of a time-based thing, do you think?
Chris Kresser: There are a number of factors that control what dysregulates the setpoint, which we’re gonna talk about, and as you say, there are some people who seem to be able to lose weight and keep it off, but statistically speaking, there is only really one treatment that we know of that reliably and substantially and durably lowers the setpoint in pretty much everybody that tries the treatment, or a vast majority of the people, and we’ll talk about that towards the end of the show. But in answer to your question, I don’t think that it’s an easy formula and certainly not black or white, and it depends on so many factors, beginning with genetics, you know, gene mutations, single gene mutations, which are relatively minor, and then epigenetic and developmental factors like I just was talking about, maternal status, maternal weight, birth weight, exposure to initial bacteria, gut flora, breast feeding, food, environmental toxins. I mean it’s so vastly complex that I don’t think there will ever be an easy, straightforward answer to that question.
Steve Wright: OK, and then did you say that the homeostatic system basically will also stimulate more hunger, as well?
Chris Kresser: Yeah, if you lose weight and you’re below what your setpoint is, then you’ll get hungrier. And that’s one of the ways that the homeostatic system regulates energy balance. You know, it’s one of the ways it tries to get you back to what it considers to be your normal weight. And that’s fine, that’s exactly how it should work in a lean person, but the problem in obesity is that the setpoint has become too high, and so the weight that the body is defending is inappropriate, and that’s again, of course, why weight loss and keeping it off is so difficult.
Why leptin is the master fat hormone and what happens when you have too much
Chris Kresser: So let’s talk about leptin because, as I’m sure most people have heard by now, leptin is really the master control hormone in this process. It is made by fat cells in proportion to body fat mass, so more body fat means you’ll be producing more leptin. And leptin basically informs the brain of changes in energy balance and the amount of energy stored as fat, so it’s a communication system where leptin signals to the brain how much energy is stored as fat, how much fat mass you have. And that leptin signal acts primarily on the hypothalamus in the brain. The hypothalamus is a little, pea-shaped gland kind of right between your eyes; if you were to extend back beyond that, that’s about where it would be. But there are also other more specific areas like the arcuate nucleus; the paraventricular nucleus; the ventromedial hypothalamic nucleus; and the lateral hypothalamic area, which is often referred to as the LHA; and then other parts of the brain that are leptin sensitive. So, clearly we know now from the last 20 years that leptin acts on several different areas of the brain, and that’s probably the main nexus of where leptin acts. So, in a normal-weight person, here’s what happens: When fat mass increases — if you go through a period of overfeeding or overeating, for example — leptin goes up, and then the brain gets the message to constrain the fat mass by reducing food intake and increasing energy expenditure, all of those mechanisms that we already talked about. And then, on the other hand, when fat mass decreases, leptin will go down, and then the brain will stimulate mechanisms that increase food intake and reduce energy expenditure and cause body fat accumulation. And so that’s how leptin regulates that homeostatic system. But in obesity, what we see is an increase of fat mass and a corresponding increase then in circulating leptin, but the appropriate response of reducing food intake and increasing energy expenditure doesn’t happen, and this suggests a state of leptin resistance, where increasing amounts of leptin are required to overcome the insensitivity to leptin in the brain. For people have heard of insulin resistance, and that’s a condition where the liver or the fat cells or the muscles cells become resistant to insulin, and the pancreas has to just continue to make more insulin in order to have the same response, in order to perform the functions that insulin should perform, because it’s basically like somebody is knocking on the door and nobody is answering, and so then they have to knock louder and louder or you have to get a couple more people to knock on the door before the person inside can actually hear it and open the door. So, that’s possible with the pancreas and insulin resistance because the pancreas can just make more insulin, right? But what happens with leptin resistance and in obesity, because leptin is produced by body fat, when there’s leptin resistance in the brain, the only way for the message to get through is for the body to increase fat stores, and that’s what will lead to a higher amount of leptin so that the message can finally get through. So, this is how leptin resistance promotes the defense of a higher setpoint for body fat mass, and we see this borne out in studies that show the genetic interventions that prevent leptin resistance in the hypothalamus will also prevent obesity, diet-induced obesity. We see this in rat studies, and we also have seen that leptin resistance precedes weight gain, so for example it can be detected in the brain even after relatively short periods of overfeeding, which suggests that it’s the leptin resistance that comes first, not the obesity.
Steve Wright: So, once you’re obese then, you don’t want to focus on more leptin, you want to focus on the leptin resistance and making new receptors.
Chris Kresser: Yeah, decreasing the factors that cause leptin resistance — and inflammation is a big one, improving leptin sensitivity, and decreasing fat mass because that’s part of what caused the problem in the first place.
The link between inflammation and obesity
Chris Kresser: Let’s talk about what causes leptin resistance then, because we just touched on it. So, one of the main causes is inflammation, and Stephan has written some good articles about this on his blog. Maybe we can link to them, as well, in the show notes. But we know that proinflammatory cytokines inhibit leptin signalling in a whole bunch of different cell types, so leptin is getting to the brain, again, but the hypothalamus can’t hear it, and then the fat mass has to increase to produce more leptin. This inflammation can be caused by a lot of different factors. There are, of course, a lot of foods that promote inflammation: processed and refined foods in particular and sugar and some unprocessed, improperly prepared grains. Gut infections that produce an increase in endotoxins like lipopolysaccharide and then intestinal permeability, which allows those endotoxins to get out of the gut and into the blood stream, that promotes inflammation and has been implicated in hypothalamic leptin resistance. Then certain micronutrient deficiencies and fatty acid imbalances can also promote inflammation and leptin resistance in the brain. And finally, another cause of leptin resistance is injury to the neurons that is, in turn, caused by accumulation of free fatty acids in the brain, and this has been shown in experiments with rodents, where researchers overfeed them, you know, they feed them a purified, which means processed, high-fat diet, and then they observe the damage to the neurons prior to the onset of obesity. So, just like leptin resistance seems to precede obesity, then the damage to the neurons also precedes obesity. So, let’s talk about now what else increases the body fat setpoint. We just discussed inflammation, and inflammation is a pretty broad term that can include causes like gut infections and intestinal permeability and environmental toxins and food toxins and micronutrient deficiencies, etc.; but there’s another main cause, I think, and this is one that Stephan has really spent a lot of time and energy highlighting on his blog, and he has taken a lot of flack for it, which I don’t really understand why. I mean, I understand people’s reaction, but I think he has presented really solid evidence supporting this. I mentioned before that the modern lifestyle is one of the primary causes of obesity, and one aspect of that lifestyle that affects weight regulation is the availability of highly energy-dense and palatable and rewarding foods. So, again, we have two systems that interact to regulate fat mass, and one is the hedonic or pleasure-seeking system and the other is the homeostatic system. And we’ve talked a bit about the homeostatic system, but the hedonic system evolved to help our hunter-gatherer ancestors seek out and take advantage of any highly palatable, energy-dense foods they happened to come upon, and its job is to make it hard to resist those foods because they’ve been so rare for most of evolutionary history. You know, having a 7-Eleven on the corner and being able to access extremely calorie-dense, rewarding, palatable foods is a very recent development on the overall scale of human history, so the hedonic system evolved at a time where that wasn’t the case, and it was to our survival advantage to be naturally drawn to those energy-dense foods and eat pretty much as much as we could of them and then store them because inevitably there were would be times where those foods were scarce and possibly even most of the time.
Are modern foods engineered to make us fat?
Chris Kresser: But, like I said, over the last 50 years in particular, there has been a huge increase in the availability of these foods and actually a systematic effort by food manufacturers to increase the reward value of food, and there’s a book that’s all about this that Stephan referenced in one of his blog posts. I can’t remember the title off the top of my head, but the book covers the intentional effort on the part of food manufacturers who hire scientists, people who really understand all of these mechanisms in depth, and they purposely engineer the food to be highly rewarding. And reward in this context is actually a term borrowed from psychology literature, which means that it reinforces a particular behavior in response to a stimuli; in this case, eating. So, eating a rewarding food makes you want to eat more of it, and there are a number of factors that influence the reward value of food — and believe me, the processed food industry has, like I said, teams of scientists that study these factors — and they include caloric density, the texture of food, the content of fat and starch and simple sugar and salt and free glutamate. They talk about it with terms like ‘mouth feel,’ like when you put a food into your mouth, how it feels in the mouth; and they study the neurobiology of it, like what centers in the brain are stimulated when you eat that particular food. It’s really quite insidious, and if you study it and become aware of how much effort has gone into this, it starts to become obvious, at least from this perspective, why there is such a dramatic increase in obesity.
Steve Wright: Is that book The End of Overeating?
Chris Kresser: It might be. Is it? Have you read it?
Steve Wright: I think it is. I’ve read that one. There’s also Mindful Eating, I believe.
Chris Kresser: I don’t think it’s Mindful Eating. It could be The End of Overeating. We’ll look it up and put it in the show notes.
Steve Wright: Yeah, if it’s that book, that book just literally blew my mind. It talks all about that, about the chemistry and the various — I think they have five variables that they rate food on.
Chris Kresser: Right, so this is a highly developed science, right? I mean, they talk about that in the book.
Steve Wright: Yeah. I think they talk about — I think it’s over a billion dollars that is kind of spent in R&D, or it’s some astronomical number that’s spent in R&D just to make us like the food, and they call it a craveability. So, they want to create foods that just — like, for some people maybe it’s a Dorito, like the Cool Ranch Doritos, or something — and they’re only looking to promote foods that are craveable. In a capitalistic, you know, consumer marketplace, that’s the only thing that’s gonna survive is that one food where you’re like, “Man, I just want some of that Cool Ranch,” or something like that.
Chris Kresser: Yeah, exactly. So, like I said, it’s an insidious and very highly developed industry. Well, we know from many animal and human studies that the reward value of a food has repeatedly been shown to influence food intake and body fatness in both animals and humans; whereas, palatability, on the other hand, is defined as the pleasure or the hedonic value associated with a food. So, when Stephan was writing this series, people got reward and palatability really confused, so let’s say again reward value reinforces a particular behavior; in this case, eating more of it; so eating a rewarding food makes you want to eat more. Whereas, a palatable food is just one that tastes good, and you know, of course, they often are related. Like, a highly palatable food might be one that is highly rewarding, in that since it tastes so good, you want to eat more of it. But it’s not necessarily to the same degree. A good example of this is steak. Steak, in my opinion, is a pretty palatable food. It tastes great. I love it. But how often do you hear somebody say, “I’m really addicted to steak. I can’t get enough steak”? People like it, they eat it, but it doesn’t tend to stimulate addictive eating behavior, right? But you do often hear people say that about chocolate or ice cream or chips and crackers. I mean, the whole Pringles thing, right? What was their slogan? “I bet you can’t eat just one.”
Steve Wright: Perfect.
Chris Kresser: Yeah! There’s a reason for that, because the scientists have designed it that way, and their marketing department is even making a baldfaced bet against you in their advertising slogan. They’re betting that your hedonic system’s evolutionary effectiveness is gonna override any willpower that you might have and that you won’t be able to eat just one, and so they’re doing everything they can to make sure that’s possible, and they’re capitalizing on our innate, you know, our evolutionary mechanism here that was designed from the beginning to be a survival advantage, but in an obesogenic environment where you have access to all these super-energy-dense, palatable, rewarding foods, that system kind of backfires.
Steve Wright: So, let me repeat that back really quick. So, palatability is just all about the food in itself and our judgement of whether it tastes good.
Chris Kresser: Right. It’s the pleasure and taste. If you find a food to be palatable, that means you like it and it tastes good.
Steve Wright: And then the reward that we’re talking about is multilevel — it’s a chemical in the brain, it’s psychological in our actions, and it potentially is also driven from, like, our ancestors in a deeper lizard brain as far as seeking certain nutrients, as well?
Chris Kresser: Well, I think they’re both driven by neurobiological mechanisms, which we’re gonna talk about a little bit more. I think that the easiest way to simplify it is that palatability doesn’t necessarily imply a change in behavior. It just means that it tastes good and you like it and you get pleasure from eating it. Whereas, food that’s rewarding will make you want to eat more, so it will actually influence your behavior. And I think, again, the really good way to piece that out in your mind is just to think of certain foods that you like the taste of but you don’t have any kind of addictive relationship with them, like steak or something. And those would tend to be foods that taste good and they’re probably part of our evolutionary history in terms of eating them, you know, like a plain sweet potato. I think most people would think a plain sweet potato tastes pretty good. It’s sweet and it’s pleasurable to eat, but how many people, again, do you know that just would go crazy eating plain sweet potatoes? It just doesn’t really happen. On the other hand, chips that have fat and salt and a particular mouth feel all engineered to stimulate the centers in your brain that motivate a particular behavior, that’s gonna have a really high reward value. Does that make sense?
Steve Wright: Yeah, it totally makes sense, and I think a lot of people listening probably in the Paleo crowd or the Specific Carbohydrate Diet crowd will relate, because I know that previously if I ate mashed potatoes or sweet potatoes I never thought of them as particularly intensely flavorful, and I think that’s just because I was eating that other stuff. Then once you drop off and you eat something that has some more carbs in it like that, you can definitely taste the sweetness and it’s much more subtle.
Chris Kresser: You got it, and I’m glad you brought that up, because one of the reasons I love this overarching theory is that it can explain why both low-carb and low-fat diets can be effective for weight loss and why when people tend to start adding carbs back if they have been on a low-carb diet or they start adding fat back when they’ve been on a low-fat diet that they tend to gain the weight back, and that’s because carbohydrates and fat have reward value on their own. And so, when you remove or really limit a whole entire class of macronutrients, that reduces the reward value of that diet. And then when you bring them back in, that increases the reward value and it tends to make you want to eat more of that. So, in your example that you just used, if you’re on a low-carb diet, which the SCD and GAPS typically are, and then you start eating carbohydrates, you’re adding reward value back to your diet, and if you had a weight problem before and the setpoint hadn’t been actually adjusted, then the chances are that you’ll gain weight back. We’re gonna talk a litte bit more about that in a moment here. So, one of the best examples of how reward and palatability affect weight regulation is something called the cafeteria diet model of rodent obesity, and this is where they give rats a bunch of human junk food, so you know, just chips, crackers, candy — it’s all human, processed food — and then they also give them an unlimited amount of the standard rat chow, which compared to the human junk food is pretty boring. And what do you suppose happens? I mean, you can probably guess. They over consume the junk food, and they don’t even touch the rat chow. And the rats that are genetically susceptible become obese, and how addicted do they get to the junk food? Well, the rats that are put on this cafeteria diet will voluntarily endure foot shocks and extreme cold just to obtain the cafeteria diet, even when the standard rat chow is freely available.
Steve Wright: That’s how good those researchers are.
Chris Kresser: Exactly! So, I mean, it’s pretty amazing, and it works the other way around, and again, we’re gonna talk about that in a second, but before we do that, I want to back up a little bit and talk at least a little about how food reward and the central nervous system interact and the regions of the brain that are involved in this, because I thinks it’s important to have a basic understanding of it. So, there are a lot of regions of the brain involved in evaluating and reinforcing the reward value of food, including the corticolimbic system, the hypothalamic system, and parts of the midbrain, and we know that signalling of dopamine and opioid peptides is especially important in the reward and hedonic value. And this kind of gets at what you were asking before, Steve. Dopamine signalling is thought to contribute particularly to reward, to the wanting of food and to the motivation to obtain food, and this is supported by the observation that changes in dopamine signalling are associated with other kinds of addictive behavior like drugs and alcohol and other substance abuse. There are lots of studies showing in drug addicts or alcoholics that there is a problem in the dopamine signalling system. We also know that interventions that alter dopamine signalling in the central nervous system have been shown to powerfully influence food intake and body fat mass, and we know that inherited or acquired reduction of dopamine signalling favors the accumulation of body fat. And one theory on this is that overexposure to these highly palatable, rewarding, and energy-dense foods desensitizes the dopamine circuits, although there is some controversy about that. Now on the other hand, opioids are connected to the liking or the hedonic value or palatability of food, and studies have shown that opioid receptor agonists — an agonist is a substance that mimics the action of a natural substance, so an opioid receptor agonist would be something that increases the effect of opioids. They strongly increase intake of palatable food in rats, so if you stimulate the opioid receptors, rats will really go crazy for palatable food. Whereas, on the other hand, opioid antagonists have the opposite effect. So, we’ve talked a lot about low-dose naltrexone on the show, but full-dose naltrexone at 50 mg is an opioid antagonist, so it completely blocks the opioid receptors, and that’s why it was used for opiate and heroin and alcohol withdrawal, because if a heroin addict, for example, is on 50 mg of naltrexone and they shoot heroin they’ll feel absolutely nothing. So, the naltrexone has been shown in clinical trials to reduce body weight because when people are taking it, they’re not inclined to eat as much palatable food, so that’s more evidence that these parts of the brain are involved.
Steve Wright: I was just going to repeat that back: So, dopamine is the craving, it’s the wanting, and then opioids are the high?
Chris Kresser: Opioids are the liking. Yeah, the hedonic — it goes to palatability. So, dopamine is connected to reward and the motivation and the behavior, and opioids are connected to the liking or the experience of pleasure or the high, yeah, if you want to put it that way. Definitely.
Steve Wright: So, that’s how LDN works, is by taking away the high, then all you’re left with is craving, and you could eat a case of chocolate and —
Chris Kresser: Well, that’s how full-dose naltrexone would work, but the problem with that is that it also, I mean, opioids are what regulate our sense of pleasure overall, so if you’re taking 50 mg of naltrexone, yeah, you won’t experience pleasure when you shoot heroin, and you won’t experience pleasure when you eat that bowl of ice cream, but you’re not going to experience much pleasure any other time. So, there are pretty obvious problems with that.
Steve Wright: Yeah.
Chris Kresser: And then a third neurochemical that’s involved in this whole process are the endocannabinoids. These are involved in the brain reward area, and of course, they earn their name after it was discovered that marijuana acts primarily through the CB1 endocannabinoid receptor. Stimulating that receptor selectively increases the consumption of highly palatable foods, and this explains, of course, why people get the munchies when they smoke pot. So, if they smoke pot and then those endocannabinoid receptors are activated, then they’re gonna want to increase palatable foods, and when people get the munchies they’re seeking out particularly palatable foods, right? They’re usually not getting the munchies for, I don’t know, brussels sprouts. I mean some people find them to be palatable. I actually like them, but it’s not the food that people tend to eat when they get the munchies, right? They’re going for the more palatable and probably more rewarding foods, as well. On the other hand, just like naltrexone, drugs that block the endocannabinoid receptors have been shown to cause weight loss and selectively suppress the consumption of highly palatable foods in rodents. So, that means it didn’t suppress consumption of all food across the board; it just selectively suppressed the consumption of the highly palatable foods. But, again, there are some problems with using this as a treatment for human obesity because these drugs are known to have psychiatric side effects including an increased risk of suicide because the endocannabinoid system probably, again, plays a role in our overall experience of pleasure and enjoyment or life. So, you have a drug that blocks those receptors, it does serve the goal of reducing consumption of palatable food, but it also, you know, really screws up people’s mood. And, of course, that’s often the problem with drugs is they suppress function. So, they suppress symptoms, but they also suppress functions, and that means that in solving one problem, they end up causing several others, because the receptors and proteins and things that drugs affect in the body don’t tend to have just one effect; they tend to have several different effects. And so, when you suppress something, you’re not just suppressing the one effect that you want to get rid of. You’re suppressing multiple effects, many of which are beneficial. So, when you put all of this together, it suggests that in an environment where humans are exposed to food that’s way more palatable and way more rewarding than what we’re adapted to, that’s when you get obesity. And I just want to reiterate that I don’t think that food reward and palatability is the only environmental factor involved in the obesity epidemic by a long shot. We’ve already talked about other factors like food environmental toxins and genetics and micronutrient deficiencies and gut flora and birth weight, etc. But I do think that reward and palatability is definitely a factor, and I think the research pretty clearly supports that it is.
The one thing any successful weight loss intervention must have
Chris Kresser: So, let’s wrap all of this up and talk a little bit about what it means for people who are trying to lose weight, and as I said in the beginning, we’re not gonna — you know, we’re already getting to the end of the show here, so we’re not gonna have time to cover this in detail, but we will revisit it later. At the simplest level, what it means is that any successful weight loss intervention has to involve lowering the setpoint. And if it doesn’t lower the setpoint, the effect is just flat-out not gonna work at all or it’s gonna work for a short period of time and then the weight will come back, and of course, that explains why something like over 90% of people who go on calorie-restricted diets end up gaining the weight back at some point, and oftentimes they gain more weight back than they lost in the first place. There is some evidence that low-carb diets and Mediterranean diets have been shown to induce moderate fat loss over the long term, and I think Paleo Diets can do that, too. There are a few studies that suggest that, but we don’t have any long-term Paleo Diet studies yet on weight loss. I certainly, you know, anecdotally in my practice have seen that, and I’m sure a lot of other people have had that experience, as well. But on the other hand, I have a lot of patients in my practice who come to me for weight loss, and they’ve been on a Paleo Diet, they lost weight to begin with, sometimes quite a bit of weight, and then they either plateau and can’t lose the last 10 or 15 pounds or they start gaining the weight back and eventually gain it all back. So, even though the Paleo Diet, I think, helps a lot of people and in some cases is the only thing that people need to lose weight and keep it off, there are clearly a lot of people whom that’s not enough for, and that’s one of the reasons I wanted to do this show, is I wanted to explain some of the mechanisms involved and help people appreciate how deeply rooted those mechanisms are, that they’re evolutionary in nature and that it’s not a failure of willpower, it’s not your fault that these systems are in place and that they work so strenuously against our efforts to lose weight. So, getting back to the setpoint, right now, as I mentioned earlier in the show, the only intervention that we know that substantially and consistently and durably, meaning in a lasting way, reduces the defended level of body fat or the setpoint is bariatric surgery or gastric bypass. So, this is a surgery where they divide the stomach into a small upper pouch and a much larger lower remnant pouch, and then they rearrange the small intestine to connect to both of these chambers. In the most popular variation of this, the small intestine is divided about 18 inches below the lower stomach outlet, and then it is rearranged into a Y-configuration, and that enables outflow of food from the small upper stomach, and what it does is it causes a rapid onset of satiation, which is feeling full. So, people who have had this surgery will feel full very quickly after they start eating, and then that is followed by growing satiety, which is an indifference to food or a lack of appetite after you’ve started eating. So, people who have had gastric bypass, on average, they lose about 60% of the excess body weight that they were carrying — at least, morbidly obese people do, and those are the ones who generally have this surgery. And in contrast to calorie restriction and other weight loss programs, the bariatric surgery causes a reduction in hunger and reduced cravings for energy-dense foods, and it doesn’t cause any change in circulating thyroid hormones that would suggest a compensatory homeostatic response to fat loss. In other words, the body doesn’t respond to this surgery in the same way that it responds to caloric restriction that I described earlier by increasing hunger and decreasing resting energy expenditure and decreasing the conversion of T4 to T3 and all of those things. And then we have studies that suggest that gastric bypass alters food reward processing in the brain, and so it’s changing the food reward system in some way, but those mechanisms aren’t entirely clear at this point. So, at this point, it may seem like I’m recommending gastric bypass, and —
Steve Wright: Are you?
Chris Kresser: I’m not really. I think it has some use in people who are extremely obese and who have tried every other way of losing weight and haven’t been able to because morbid obesity along with extreme, you know, metabolic syndrome is a real significant risk factor for a number of different diseases that can kill you. So, in those situations, gastric bypass might actually be a valid alternative, but I’m not bringing it up to suggest it for people who are just trying to lose a little bit of weight or are even 10, 20, 30, 40, 50 pounds overweight. I don’t think it’s a viable alternative in that situation. There are risks, of course, associated with any invasive procedure like that, and you know, I’m more talking about this as a way of, first of all, just sharing what this surgery and what happens after it can tell us about the setpoint and other interventions that might help to lower the setpoint, because at this point that’s not altogether clear. And that’s the million dollar question, really. I talked earlier about how we just haven’t cracked the nut yet in this whole weight loss thing, and whoever figures out what nonsurgical method can reliably lower the setpoint is gonna get the Nobel Prize and be a multi-billionaire — if there even is such a, I mean, I frankly don’t think that there is gonna be just one thing and that it’s that simple because this is so complex.
Steve Wright: Yeah, I think you made it pretty clear that this is pretty complex, and any thought that a surgery could just magically turn things around — because I think there is a lot of new stuff coming out now about long-term studies with the bypass surgeries, and they’re having onset of other diseases because of lack of nutrients now and that kind of thing.
Chris Kresser: Absolutely. Those are the complications that I was referring to, so there’s no magic bullet. It does work for weight loss, that’s for sure, but as you pointed out, there are a lot of other problems that the surgery causes, and there is a lot more to health than weight. There are some other interventions, though, that might lower the setpoint that research supports, and Stephan, again, of course, has written about this. Just as increased food reward and palatability can increase the setpoint, there are studies that suggest that decreased reward and palatability lowers it in both rodents and humans. And Stephan blogged about a really great 1965 paper that was published in the Annals of the New York Academy of Sciences, and in this study researchers developed a machine that basically dispenses bland liquid food through a tube at the push of a button, and it was kind of like sci-fi, if you look at the picture; it’s pretty funny. And the formula was 50% carbohydrate, 20% protein, and 30% fat. So, at first they fed two lean people with no weight problems for 16 and 9 days, respectively, and both people maintained their typical caloric intake and weight eating this really bland liquid food. And then they fed morbidly obese volunteers, and over the first 18 days, one obese volunteer ate only 275 calories a day, and the second volunteer ate even less, 144 calories a day over 12 days, and that person lost 23 pounds in 12 days. The first volunteer continued eating from the machine for 70 more days in the ward and lost 70 pounds total in that 70 days, and then he was sent home with the formula and instructed to eat about 400 calories a day with it for another 185 days, and he ended up losing 200 pounds in that 185-day period and, remarkably, never complained of hunger or GI discomfort. So, some people might say, yeah, big deal; of course you’re gonna eat less food when it’s not palatable or rewarding. But that doesn’t explain why the lean people maintained their weight and their caloric intake on that diet, because if both lean and obese people ate less of it, then you would expect the lean people to lose weight, but they ate the same amount of it, and they maintained their weight over that period of time. And then there was another study in 1976 that confirmed that reducing food reward by feeding bland food lowers the body fat setpoint in humans. So, all of this implies that, of course, highly rewarding food can increase the body fat setpoint in certain susceptible people, not in everybody, and that food with few rewarding properties can allow them to return to a lean state, and that doesn’t happen necessarily with everybody either. And there’s also some evidence that suggests another technique called the protein sparing modified fast may reset the setpoint, but we’re out of time here, so we can’t talk about that in any detail. Before we close, I just want to say a brief word about genetics. There’s absolutely no doubt, as I’ve said a few times already, that genetics play a role in fat gain and fat loss, but how much is the question. We know that heritable factors, when you combine genetics and epigenetics, are estimated to account for somewhere between 45% and 75% of body mass index variability. But we also know that monogenic disorders, which mean mutations of one single gene, account for less than 5% of obesity, and some estimates say it’s even less than 2%. So, this means, of course, that obesity is a polygenic trait, which means that it involves both developmental and epigenetic factors, as well as genetics, and we’ve talked about some of those before. Things like low birth weight and maternal obesity and maternal overnutrition can increase subsequent obesity risk. And likewise, prepregnancy fat loss, like women who have had the bariatric surgery before they get pregnant, tends to reduce the future risk of obesity. So, this suggests that genetics do play a role, but that role is pretty small on its own but pretty large when you combine genes with environmental and developmental factors. So, again, it’s the interaction of the genes and the environment that really makes a difference. OK, I think that’s it!
Steve Wright: Yeah, that’s pretty powerful! So, the moral of the story is that you could have been set up from the beginning, unbeknownst to you, from genetics. And there are a bunch of scientists and a large, billion dollar industry that are trying to set you up on the corner, and so you definitely need to get some help, right?
Chris Kresser: That’s it! I hope that the effect of this — one interpretation of this is to get really depressed and say, “Wow! It’s just pointless to even try to lose weight.” But I hope that’s not the result of this. My intention was that people who have been having a hard time might be able to find some more compassion for themselves, because if you think about the forces you’re up against — as you pointed out, so you’ve got genetics, genetic predisposition. Then you’ve got epigenetic factors that start from before you were even born. I mean they basically start at conception or even before conception with your mom’s nutritional status during her pregnancy and then your birth and the manner of your birth and whether you were breastfed and your early exposure to all of these environmental factors. And then you encounter the food industry, which, like you said, is on every corner, trying to get you to eat these highly energy-dense, palatable foods, and that is interacting with all kinds of neurobiological mechanisms, opioids, endocannabinoids, dopamine, and the whole hedonic, pleasure-seeking system that we’ve had as part of our wiring for millions of years. So, when you put all that together, I hope it leads to just an appreciation of the difficulty of the task and maybe some compassion for yourself if you’re struggling with this for why it is so difficult, and hopefully in the future we’ll get a chance to dive more into what can be done about it, and I will frankly say that weight loss is difficult. It’s one of the hardest things for me to treat in my practice. I’m experimenting with some different programs designed to reduce the body fat setpoint, and sometimes they’re successful and sometimes they’re not. And I’d be really suspicious of anybody who claims to have a program that works for everybody.
Steve Wright: Yeah, I hope this isn’t depressing either. I hope this is eye-opening, as you said, and I think it should be eye-opening in the fact that there is no magic pill. There’s not a magic pill that’s even in testing that could come, and the appreciation that it’s a multifaceted problem, which means that the answer is likely multifaceted. So, it’s a food problem; therefore, there’s gonna be a food answer. It’s potentially a psychological problem; there might be a psychological component. It’s a chemical problem; there’s probably a chemical answer. And altogether, I think it should be encouraging to take multiple steps in every area.
Chris Kresser: Yeah, that’s very well said, and the takeaway is that it’s extremely individual, and it’s really important to first identify what all the mechanisms are in each individual case and then address those one by one, and that’s, of course, why there is, again, no magic bullet that works for everybody in the same way. OK, so thanks everybody for listening, and we’ll see you next time!
Steve Wright: Yeah, it’s been a great show! OK, so if you’re confused about what to eat, which, after the show, you might be, check out the PersonalPaleoCode. It’s a 3-step program designed to help you discover your own ideal diet and create highly customized meal plans with a few clicks of a button. You can visit PersonalPaleoCode.com to learn more. And if you’re trying to get pregnant or are already pregnant or nursing, don’t miss out on The Healthy Baby Code. It guides you through the essential steps to naturally boost fertility and promote lifelong health for you and your baby. Find out more at HealthyBabyCode.com.