[Content note: food, dieting, obesity]

I.

The Hungry Brain gives off a bit of a Malcolm Gladwell vibe, with its cutesy name and pop-neuroscience style. But don’t be fooled. Stephan Guyenet is no Gladwell-style dilettante. He’s a neuroscientist studying nutrition, with a side job as a nutrition consultant, who spends his spare time blogging about nutrition, tweeting about nutrition, and speaking at nutrition-related conferences. He is very serious about what he does and his book is exactly as good as I would have hoped. Not only does it provide the best introduction to nutrition I’ve ever seen, but it incidentally explains other neuroscience topics better than the books directly about them do.

I first learned about Guyenet’s work from his various debates with Gary Taubes and his supporters, where he usually represents the “scientific consensus” side. He is very careful to emphasize that the consensus doesn’t look anything like Taubes’ caricature of it. The consensus doesn’t believe that obesity is just about weak-willed people voluntarily choosing to eat too much, or that obese people would get thin if they just tried diet and exercise, or that all calories are the same. He writes

The [calories in, calories out] model is the idea that our body weight is determined by voluntary decisions about how much we eat and move, and in order to control our body weight, all we need is a little advice about how many calories to eat and burn, and a little willpower. The primary defining feature of this model is that it assumes that food intake and body fatness are not regulated. This model seems to exist mostly to make lean people feel smug, since it attributes their leanness entirely to wise voluntary decisions and a strong character. I think at this point, few people in the research world believe the CICO model. [Debate opponent Dr. David] Ludwig and I both agree that it provides a poor fit for the evidence. As an alternative, Ludwig proposes the insulin model, which states that the primary cause of obesity is excessive insulin action on fat cells, which in turn is caused principally by rapidly-digesting carbohydrate. According to this model, too much insulin reduces blood levels of glucose and fatty acids (the two primary circulating metabolic fuels), simultaneously leading to hunger, fatigue, and fat gain. Overeating is caused by a kind of “internal starvation”. There are other versions of the insulin model, but this is the one advocated by Ludwig (and Taubes), so it will be my focus. But there’s a third model, not mentioned by Ludwig or Taubes, which is the one that predominates in my field. It acknowledges the fact that body weight is regulated, but the regulation happens in the brain, in response to signals from the body that indicate its energy status. Chief among these signals is the hormone leptin, but many others play a role (insulin, ghrelin, glucagon, CCK, GLP-1, glucose, amino acids, etc.)

The Hungry Brain is part of Guyenet’s attempt to explain this third model, and it basically succeeds. But like many “third way” style proposals, it leaves a lot of ambiguity. With CICO, at least you know where you stand – confident that everything is based on willpower and that you can ignore biology completely. And again, with Taubes, you know where you stand – confident that willpower is useless and that low-carb diets will solve everything. The Hungry Brain is a little more complicated, a little harder to get a read on, and at times pretty wishy-washy.

But listening to people’s confidently-asserted simple and elegant ideas was how we got into this mess, so whatever, let’s keep reading.

II.

The Hungry Brain begins with the typical ritual invocation of the obesity epidemic. Did you know there are entire premodern cultures where literally nobody is obese? That in the 1800s, only 5% of Americans were? That the prevalence of obesity has doubled since 1980?

Researchers have been keeping records of how much people eat for a long time, and increased food intake since 1980 perfectly explains increased obesity since 1980 – there is no need to bring in decreased exercise or any other factors. Exercise has decreased since the times when we were all tilling fields ten hours a day, but for most of history, as our exercise decreased, our food intake decreased as well. But for some reason, starting around 1980, the two factors uncoupled, and food intake started to rise despite exercise continuing to decrease.

Guyenet discusses many different reasons this might have happened, including stress-related overeating, poor sleep, and quick prepackaged food. But the ideas he keeps coming back to again and again are food reward and satiety.

In the 1970s, scientists wanted to develop new rat models of obesity. This was harder than it sounded; rats ate only as much as they needed and never got fat. Various groups tried to design various new forms of rat chow with extra fat, extra sugar, et cetera, with only moderate success – sometimes they could get the rats to eat a little too much and gradually become sort of obese, but it was a hard process. Then, almost by accident, someone tried feeding the rats human snack food, and they ballooned up to be as fat as, well, humans. The book:

Palatable human food is the most effective way to cause a normal rat to spontaneously overeat and become obese, and its fattening effect cannot be attributed solely to its fat or sugar content.

So what does cause this fattening effect? I think the book’s answer is “no single factor, but that doesn’t matter, because capitalism is an optimization process that designs foods to be as rewarding as possible, so however many different factors there are, every single one of them will be present in your bag of Doritos”. But to be more scientific about it, the specific things involved are some combination of sweet/salty/umami tastes, certain ratios of fat and sugar, and reinforced preferences for certain flavors.

Modern food isn’t just unusually rewarding, it’s also unusually bad at making us full. The brain has some pretty sophisticated mechanisms to determine when we’ve eaten enough; these usually involve estimating food’s calorie load from its mass and fiber level. But modern food is calorically dense – it contains many more calories than predicted per unit mass – and fiber-poor. This fools the brain into thinking that we’re eating less than we really are, and shuts down the system that would normally make us feel full once we’ve had enough. Simultaneously, the extremely high level of food reward tricks the brain into thinking that this food is especially nutritionally valuable and that it should relax its normal constraints.

Adding to all of this is the so-called “buffet effect”, where people will eat more calories from a variety of foods presented together than they would from any single food alone. My mother likes to talk about her “extra dessert stomach”, ie the thing where you can gorge yourself on a burger and fries until you’re totally full and couldn’t eat another bite – but then mysteriously find room for an ice cream sundae afterwards. This is apparently a real thing that’s been confirmed in scientific experiments, and a major difference between us and our ancestors. The !Kung Bushmen, everyone’s go-to example of an all-natural hunter-gatherer tribe, apparently get 50% of their calories from a single food, the mongongo nut, and another 40% from meat. Meanwhile, we design our meals to include as many unlike foods as possible – for example, a burger with fries, soda, and a milkshake for dessert. This once again causes the brain to relax its usual strict constraints on appetite and let us eat more than we should.

The book sums all of these things up into the idea of “food reward” making some foods “hyperpalatable” and “seducing” the reward mechanism in order to produce a sort of “food addiction” that leads to “cravings”, the “obesity epidemic”, and a profusion of “scare quotes”.

I’m being a little bit harsh here, but only to highlight a fundamental question. Guyenet goes into brilliant detail about things like the exact way the ventral tegmental area of the brain responds to food-related signals, but in the end, it all sounds suspiciously like “food tastes good so we eat a lot of it”. It’s hard to see where exactly this differs from the paradigm that he dismisses as “attributing leanness to wise voluntary decisions and a strong character…to make lean people feel smug”. Yes, food tastes good so we eat a lot of it. And Reddit is fun to read, but if someone browses Reddit ten hours a day and doesn’t do any work then we start speculating about their character, and maybe even feeling smug. This part of the book, taken alone, doesn’t really explain why we shouldn’t be doing that about weight too.

III.

There is only one fat person on the Melanesian island of Kitava – a businessman who spends most of his time in modern urbanized New Guinea, eating Western food. The Kitavans have enough food, and they live a relaxed tropical lifestyle that doesn’t demand excessive exercise. But their bodies match caloric intake to expenditure with impressive precision. So do the !Kung with their mongongo nuts, Inuit with their blubber, et cetera.

And so do Westerners who limit themselves to bland food. In 1965, some scientists locked people in a room where they could only eat nutrient sludge dispensed from a machine. Even though the volunteers had no idea how many calories the nutrient sludge was, they ate exactly enough to maintain their normal weight, proving the existence of a “sixth sense” for food caloric content. Next, they locked morbidly obese people in the same room. They ended up eating only tiny amounts of the nutrient sludge, one or two hundred calories a day, without feeling any hunger. This proved that their bodies “wanted” to lose the excess weight and preferred to simply live off stored fat once removed from the overly-rewarding food environment. After six months on the sludge, a man who weighed 400 lbs at the start of the experiment was down to 200, without consciously trying to reduce his weight.

In a similar experiment going the opposite direction, Ethan Sims got normal-weight prison inmates to eat extraordinary amounts of food – yet most of them still had trouble gaining weight. He had to dial their caloric intake up to 10,000/day – four times more than a normal person – before he was able to successfully make them obese. And after the experiment, he noted that “most of them hardly had any appetite for weeks afterward, and the majority slimmed back down to their normal weight”.

What is going on here? Like so many questions, this one can best be solved by grotesque Frankenstein-style suturing together of the bodies of living creatures.

In the 1940s, scientists discovered that if they damaged the ventromedial hypothalamic nucleus (VMN) of rats, the rats would basically never stop eating, becoming grotesquely obese. They theorized that the VMN was a “satiety center” that gave rats the ability to feel full; without it, they would feel hungry forever. Later on, a strain of mutant rats was discovered that seemed to naturally have the same sort of issue, despite seemingly intact hypothalami. Scientists wondered if there might be a hormonal problem, and so they artificially conjoined these rats to healthy normal rats, sewing together their circulatory systems into a single network. The result: when a VMN-lesioned rat was joined to a normal rat, the VMN-lesioned rat stayed the same, but the normal rat stopped eating and starved to death. When a mutant rat was joined to a normal rat, the normal rat stayed the same and the mutant rat recovered and became normal weight.

The theory they came up with to explain the results was this: fat must produce some kind of satiety hormone, saying “Look, you already have a lot of fat, you can feel full and stop eating now”. The VMN of the hypothalamus must detect this message and tell the brain to feel full and stop eating. So the VMN-lesioned rats, whose detector was mostly damaged, responded by never feeling full, eating more and more food, and secreting more and more (useless) satiety hormone. When they were joined to normal rats, their glut of satiety hormones flooded the normal rats – and their normal brain, suddenly bombarded with “YOU ALREADY HAVE WAY TOO MUCH FAT” messages, stopped eating entirely.

The mutant rats, on the other hand, had lost the ability to produce the satiety hormone. They, too, felt hungry all the time and ate everything. But when they were joined to a normal rat, the normal levels of satiety hormone flowed from the normal rat into the mutant rat, reached the fully-functional detector in their brains, and made them feel full, curing their obesity.

Skip over a lot of scientific infighting and unfortunate priority disputes and patent battles, and it turns out the satiety hormone is real, exists in humans as well, and is called leptin. A few scientists managed to track down some cases of genetic leptin deficiency in humans, our equivalent of the mutant rats, and, well…

Usually they are of normal birth weight and then they’re very, very hungry from the first weeks and months of life. By age one, they have obesity. By age two, they weigh 55-65 pounds, and their obesity only accelerates from there. While a normal child may be about 25% fat, and a typical child with obesity may be 40% fat, leptin-deficient children are up to 60% fat. Farooqi explains that the primary reason leptin-deficient children develop obesity is that they have “an incredible drive to eat”…leptin-deficient children are nearly always hungry, and they almost always want to eat, even shortly after meals. Their appetite is so exaggerated that it’s almost impossible to put them on a diet: if their food is restricted, they find some way to eat, including retrieving stale morsels from the trash can and gnawing on fish sticks directly from the freezer. This is the desperation of starvation […] Unlike normal teenagers, those with leptin deficiency don’t have much interest in films, dating, or other teenage pursuits. They want to talk about food, about recipes. “Everything they do, think about, talk about, has to do with food” says [Dr.] Farooqi. This shows that the [leptin system] does much more than simply regulate appetite – it’s so deeply rooted in the brain that it has the ability to hijack a broad swath of brain functions, including emotions and cognition.

It’s the leptin-VNM-feedback system (dubbed the “lipostat”) that helps people match their caloric intake to their caloric requirements so impressively. The lipostat is what keeps hunter-gatherers eating exactly the right number of mongongo nuts, and what keeps modern Western overeaters at much closer to the right weight than they could otherwise expect.

The lipostat-brain interface doesn’t just control the raw feeling of hunger, it seems to have a wide range of food-related effects, including some on higher cognition. Ancel Keys (of getting-blamed-for-everything fame) ran the Minnesota Starvation Experiment on some unlucky conscientious objectors to World War II. He starved them until they lost 25% of their body weight, and found that:

Over the course of their weight loss, Keys’s subjects developed a remarkable obsession with food. In addition to their inescapable, gnawing hunger, their conversations, thoughts, fantasies, and dreams revolved around food and eating – part of a phenomenon Keys called “semistarvation neurosis”. They became fascinated by recipes and cookbooks, and some even began collecting cooking utensils. Like leptin-deficient adolescents, their lives revolved around food. Also like leptin-deficient adolescents, they had very low leptin levels due to their semi-starved state.

Unsurprisingly, as soon as the experiment ended, they gorged themselves until they were right back at their pre-experiment weights (but no higher), at which point they lost their weird food obsession.

Just as a well-functioning lipostat is very good at keeping people normal weight, a malfunctioning lipostat is very good at keeping people obese. Fat people seem to have “leptin resistance”, sort of like the VMN-lesioned rats, so that their bodies get confused about how much fat they have. Suppose a healthy person weighs 150 lbs, his body is on board with that, and his lipostat is set to defend a 150 lb set point. Then for some reason he becomes leptin-resistant, so that the brain is only half as good at detecting leptin as it should be. Now he will have to be 300 lbs before his brain “believes” he is the right weight and stops encouraging him to eat more. If he goes down to a “mere” 250 lbs, then he will go into the same semistarvation neurosis as Ancel Keys’ experimental subjects and become desperately obsessed with food until they get back up to 300 again. Or his body will just slow down metabolism until his diet brings him back up. Or any of a bunch of other ways the lipostat has to restore weight when it wants to.

This explains the well-known phenomenon where contestants on The Biggest Loser who lose 200 or 300 pounds for the television camera pretty much always gain it back after the show ends. Even though they’re highly motivated and starting from a good place, their lipostat has seized on their previous weight as the set point it wants to defend, and resisting the lipostat is somewhere between hard and impossible. As far as I know, nobody has taken Amptoons up on their challenge to find a single peer-reviewed study showing any diet that can consistently bring fat people to normal weight and keep them there. After a certain level of lipostat dysregulation, “solving” weight problems by diet and exercise becomes hard-to-impossible, and the people who loudly insist otherwise tend to kind of be jerks.

And alas, it doesn’t seem to work to just inject leptin directly. As per Guyenet

People with garden variety obesity already have high levels of leptin…while leptin therapy does cause some amount of fat loss, it requires enormous doses to be effective – up to forty times the normal circulating amount. Also troubling is the extremely variable response, with some people losing over thirty pounds and others losing little or no weight. This is a far cry from the powerful fat-busting effect of leptin in rodents. [Leptin as] the new miracle weight-loss drug never made it to market. This disappointment forced the academic and pharmaceutical communities to confront a distressing possibility: the leptin system defends vigorously against weight loss, but not so vigorously against weight gain. “I have always thought, and continue to believe,” explained [leptin expert Rudy] Leibel, “that the leptin hormone is really a mechanism for detecting deficiency, not excess.” It’s not designed to constrain body fatness, perhaps because being too fat is rarely a problem in the wild. Many researchers now believe that while low leptin levels in humans engage a powerful starvation response that promotes fat gain, high leptin levels don’t engage an equally powerful response that promotes fat loss. Yet something seems to oppose rapid fat gain, as Ethan Sims’ overfeeding studies (and others) have shown. Although leptin clearly defends the lower limit of adiposity, the upper limit may be defended by an additional, unidentified factor – in some people more than others.

This is the other half of the uncomfortable dichotomy that makes me characterize The Hungry Brain as “wishy-washy”. The lipostat is a powerful and essentially involuntary mechanism for getting weight exactly where the brain wants, whether individual dieters are cooperative or not. Here it looks like obesity is nobody’s fault, unrelated to voluntary decisions, and that the standard paradigm really is just an attempt by lean people to feel smug. Practical diet advice starts to look like “inject yourself with quantities of leptin so massive that they overcome your body’s resistance”. How do we connect this with the other half of the book, the half with food reward and satiety and all that?

IV.

With more rat studies!

Dr. Barry Levin fed rats either a healthy-rat-food diet or a hyperpalatable-human-food diet, then starved and overfed them in various ways. He found that the rats defended their obesity set points in the expected manner, but that the same rats defend different set points depending on their diets. Rats on healthy-rat-food defended a low, healthy-for-rats set point; rats on hyperpalatable-human-food defended a higher set point that kept them obese.

That is, suppose you give a rat as much Standardized Food Product as it can eat. It eats until it weighs 8 ounces, and stays that weight for a while. Then you starve it until it only weighs 6 ounces, and it’s pretty upset. Then you let it eat as much as it wants again, and it overeats until it gets back to 8 ounces, then eats normally and maintains that weight.

But suppose you get a rat as many Oreos as it can eat. It eats until it weighs 16 ounces, and stays that weight for a while. Then you starve it until it only weighs 6 ounces. Then you let it eat as much as it wants again, and this time it overeats until it gets back to 16 ounces, and eats normally to maintain that weight.

Something similar seems to happen with humans. A guy named Michel Cabanac ran an experiment in which he put overweight people on two diets. In the first diet, they ate Standardized Food Product, and naturally lost weight since it wasn’t very good and they didn’t eat very much of it. In the second diet, he urged people to eat less until they matched the first group’s weight loss, but to keep eating the same foods as normal – just less of them. The second group reported being hungry and having a lot of trouble dieting; the first group reported not being hungry and not having any trouble at all.

Guyenet concludes:

Calorie-dense, highly rewarding food may favor overeating and weight gain not just because we passively overeat it but also because it turns up the set point of the lipostat. This may be one reason why regularly eating junk food seems to be a fast track to obesity in both animals and humans…focusing the diet on less rewarding foods may make it easier to lose weight and maintain weight loss because the lipostat doesn’t fight it as vigorously. This may be part of the explanation for why all weight-loss diets seem to work to some extent – even those that are based on diametrically opposed principles, such as low-fat, low-carbohydrate, paleo, and vegan diets. Because each diet excludes major reward factors, they may all lower the adiposity set point somewhat.

(this reminds me of the Shangri-La Diet, where people would drink two tablespoons of olive oil in the morning, then find it was easy to diet without getting hungry during the day. People wondered whether maybe the tastelessness of the olive oil had something to do with it. Could it be that the olive oil is temporarily bringing the lipostat down to its “bland food” level?)

Why should some food make the lipostat work better than other food? Guyenet now gets to some of his own research, which is on a type of brain cell called a POMC neuron. These neurons produce various chemicals, including a sort of anti-leptin called Neuropeptide Y, and they seem to be a very fundamental part of the lipostat and hunger system. In fact, if you use superprecise chemical techniques to kill NPY neurons but nothing else, you can cure obesity in rats.

The area of the hypothalamus with POMC neurons seem to be damaged in overweight rats and overweight humans. Microglia and astrocytes, the brain’s damage-management and repair cells, proliferated in appetite-related centers, but nowhere else. Maybe this literal damage corresponds to the metaphorically “damaged” lipostat that’s failing to maintain weight normally, or the “damaged” leptin detector that seems to be misinterpreting the body’s obesity?

In any case, eating normal rat food for long enough appears to heal this damage:

Our results suggest that obese rodents suffer from a mild form of brain injury in an area of the brain that’s critical for regulating food intake and adiposity. Not only that, but the injury response and inflammation that developed when animals were placed on a fattening diet preceded the development of obesity, suggesting that this brain injury could have played a role in the fattening process.

Guyenet isn’t exactly sure what aspect of modern diets cause the injury:

Many researchers have tried to narrow down the mechanisms by which this food causes changes in the hypothalamus and obesity, and they have come up with a number of hypotheses with varying amounts of evidence to support them. Some researchers believe the low fiber content of the diet precipitates inflammation and obesity by its adverse effects on bacterial populations in the gut (the gut microbiota). Others propose that saturated fat is behind the effect, and unsaturated fats like olive oil are less fattening. Still others believe the harmful effects of overeating itself, including the inflammation caused by excess fat and sugar in the bloodstream and in cells, may affect the hypothalamus and gradually increase the set point. In the end, these mechanisms could all be working together to promote obesity. We don’t know all the details yet, but we do know that easy access to refined, calorie-dense, highly rewarding food leads to fat gain and insidious changes in the lipostat in a variety of species, including humans. This is particularly true when the diet offers a wide variety of sensory experiences, such as the hyperfattening “cafeteria diet” we encountered in chapter 1. Personally, I believe overeating itself probably plays an important role in the process that increases the adiposity set point. In other words, repeated bouts of overeating don’t just make us fat; they make our bodies want to stay fat. This is consistent with the simple observation that in the United States, most of our annual weight gain occurs during the six-week holiday feasting period between Thanksgiving and the new year, and that this extra weight tends to stick with us after the holidays are over…because of some combination of food quantity and quality, holiday feasting ratchets up the adiposity set point of susceptible people a little bit each year, leading us to gradually accumulate and defend a substantial amount of fat. Since we also tend to gain weight at a slower rate during the rest of the year, intermittent periods of overeating outside of the holidays probably contribute as well. How might this happen? We aren’t entirely sure, but researchers, including Jeff Friedman, have a possible explanation: excess leptin itself may contribute to leptin resistance. To understand how this works, I need to give you an additional piece of information: Leptin doesn’t just correlate with body fat levels; it also responds to short-term changes in calorie intake. So if you overeat for a few days, your leptin level can increase substantially, even if your adiposity has scarcely changed (and after your calorie intake goes back to normal, so does your leptin). As an analogy for how this can cause leptin resistance, imagine listening to music that’s too loud. At first, it’s thunderous, but eventually, you damage your hearing, and the volume drops. Likewise, when we eat too much food over the course of a few days, leptin levels increase sharply, and this may begin to desensitize the brain circuits that respond to leptin. Yet Rudy Leibel’s group has also shown that high leptin levels alone aren’t enough – the hypothalamus also seems to require a second “hit” for high leptin to increase the set point of the lipostat. This second hit could be the brain injury we, and others, have identified in obese rodents and humans.

And he isn’t sure exactly what aspect of the normal rodent diet promotes the healing:

I did do some research in mice suggesting that unrefined, simple food does reverse the brain changes and the obesity. I don’t claim that it’s all attributable to the blandness though– the two diets differed in many respects (palatability, calorie density, fiber content, macronutrient profile, fatty acid profile, content of nonessential nutrients like polyphenols). Also, we don’t know how well the finding applies to humans yet. One of the problems is that it’s very hard to get a group of humans to adhere strictly to a whole food diet for long enough to study its long-term effects on appetite and body fatness. People are very attached to the pleasures of the palate!

But all of this together seems to point to a potential synthesis between the hyperpalatability and lipostat models. For most of human history, the lipostat faced only mild stresses and was able to maintain a normal weight without much trouble. Modern society has been incentivized to produce hyperpalatable, low-satiety food as superstimuli. This modern food is able to overwhelm normal satiety cues and produce short-term overeating. And for some reason this short-term overeating raises the lipostat’s set point (maybe because of brain damage and leptin resistance), causing long-term weight gain in a way that is very difficult to reverse.

V.

But I still have trouble reconciling these two points of view.

A couple of days ago, I walked by an ice cream store. I’d just finished lunch, and I wasn’t very hungry at the time, but it looked like really good ice cream, and it was hot out, so I gave in to temptation and ate a 700 calories sundae. Does this mean:

1. Based on the one pound = 3500 calories heuristic, I have now gained 0.2 lbs. That extra weight will stay with me my whole life, or at least until some day when I diet and eat 700 calories less than my requirement. If I were to eat ice cream like this a hundred times, I would gain twenty pounds.

2. My lipostat adjusts for the 700 extra calories, and causes me to exercise more, or ramp up my metabolism, or burn more brown fat, or eat less later on, or something. I don’t gain any weight, and eating the ice cream was that rarest of all human experiences, a completely guiltless pleasure. I should eat ice cream whenever I feel like it, or else I am committing the sin of denying myself a lawful pleasure.

3. My lipostat will more or less take care of the ice cream today, and I won’t notice the 0.2 pounds on the scale, but it is very gradually doing hard-to-measure damage to my hypothalamus, and if I keep eating ice cream like this, then one day when I’m in my forties I’m going to wake up weighing three hundred pounds, and no diet will ever be able to help me.

4. Not only will I gain 0.2 pounds immediately, but my lipostat will adjust to want to be 0.2 pounds heavier, and I will never lose it, even if I try really hard to diet later.

5. The above scenario is impossible. Even if I think I just ate ice cream because it looked good, in reality I was driven to do it by my lipostat’s quest for caloric balance. Any feeling of choice in the matter is an illusion.

I think the reason this is so confusing is because the real answer is “it could be any one of these, depending on genetics.”

Note the position of the grey squares representing BMI

Right now, within this culture, variation in BMI is mostly genetic. This isn’t to say that non-genetic factors aren’t involved – the difference between 1800s America and 2017 America is non-genetic, and so is the difference between the perfectly-healthy Kitavans on Kitava and the one Kitavan guy who moved to New Guinea. But once everyone alike is exposed to the 2017-American food environment, differences between the people in that environment seem to be really hereditary and not-at-all-related to learned behavior. Guyenet acknowledges this:

Genes explain that friend of yours who seems to eat a lot of food, never exercises, and yet remains lean. Claude Bouchard, a genetics researcher at the Pennington Biomedical Research Center in Baton Rouge, Louisiana, has shown that some people are intrinsically resistant to gaining weight even when they overeat, and that this trait is genetically influenced. Bouchard’s team recruited twelve pairs of identical twins and overfed each person by 1,000 calories per day above his caloric needs, for one hundred days. In other words, each person overate the same food by the same amount, under controlled conditions, for the duration of the study. If overeating affects everyone the same, then they should all have gained the same amount of weight. Yet Bouchard observed that weight gain ranged from nine to twenty-nine pounds! Identical twins tended to gain the same amount of weight and fat as each other, while unrelated subjects had more divergent responses…Not only do some people have more of a tendency to overeat than others, but some people are intrinsically more resistant to gaining fat even if they do overeat. The research of James Levine, an endocrinologist who works with the Mayo Clinic and Arizona State University, explains this puzzling phenomenon. In a carefully controlled overfeeding study, his team showed that the primary reason some people readily burn off excess calories is that they ramp up a form of calorie-burning called “non-exercise activity thermogenesis” (NEAT). NEAT is basically a fancy term for fidgeting. When certain people overeat, their brains boost calorie expenditure by making them fidget, change posture frequently, and make other small movements throughout the day. It’s an involuntary process, and Levine’s data show that it can incinerate nearly 700 calories per day. The “most gifted” of Levine’s subjects gained less than a pound of body fat from eating 1,000 extra calories per day for eight weeks. Yet the strength of the response was highly variable, and the “least gifted” of Levine’s subjects didn’t increase NEAT at all, shunting all the excess calories into fat tissue and gaining over nine pounds of body fat… Together, these studies offer indisputable evidence that genetics plays a central role in obesity and dispatch the idea that obesity is primarily due to acquired psychological traits.

These studies suggest that one way genetics affects obesity is by altering the tolerance level of the lipostat. Genetically privileged people may have very finicky lipostats that immediately burn off any extra calories they eat, and which never become dysregulated. Genetically unlucky people may have weak lipostats which fail to defend against weight gain, or which are too willing to adjust their set point up in the presence of an unhealthy food environment.

So, given how many people seem to have completely different weight-gain-related experiences to each other, the wishy-washyness here might be a feature rather than a bug.

One reason I’ve always found genetics so exciting is that there are all these fields – nutrition is a great example, but this applies at least as much to psychiatry – where everyone has wildly different personal experiences, and where there’s a large and vocal population of people who say that the research is exactly the opposite of their lived experiences. People have tried to shoehorn the experiences to fit the research, with various levels of plausibility and condescendingness. And for some reason, it’s always really hard to generate the hypothesis “people’s different experiences aren’t an illusion; people are genuinely really different”. Once you start looking at genetics, everything sort of falls into place, and ideas which seemed wishy-washy or self-contradictory before are revealed as just reflecting the diversity of nature. People who were previously at each other’s throats disputing different interpretations of the human condition are able to peacefully agree that there are many different human conditions, and that maybe we can all just get along. The Hungry Brain and other good books in its vein offer a vision for how we might one day be able to do that in nutrition science.

VI.

Lest I end on too positive a note, let me reiterate the part where happiness is inherently bad and a sort of neo-Puritan asceticism is the only way to avoid an early grave.

There’s a sort of fatalism to talking about “food reward”. If the enemy were saturated fat, we could just stick with the sugary sweetness of Coca-Cola. If the enemy were carbohydrates, we could go out for steak every night. But what do we do if the enemy is deliciousness itself?

A few weeks ago Guyenet announced The Bland Food Cookbook, a collection of tasteless recipes guaranteed to be low food-reward and so discourage overeating. It was such a natural extension of his philosophy that it took me a whole ten seconds to realize it was an April Fools joke. But why should it be? Shouldn’t this be exactly the sort of thing we’re going for?

I asked him, and he responded that:

If I thought enough people would actually be capable of following the diet, I would consider making such a cookbook non-ironically. The second point I want to make here is that there are many ways to lose weight, and deliberately reducing food reward is only one of them. You could also exercise, eat a low-calorie-density diet, eat a high-protein diet, restrict a macronutrient, restrict animal foods, restrict plant foods, eat nothing but potatoes. Most approaches overlap with a low-reward diet to varying degrees, but I don’t think the low reward value encapsulates everything about why every weight loss strategy works. BTW, low-carb folks often have a knee-jerk reaction to the low-reward thing that goes something like this: “I eat food that’s delicious, such as steaks, bacon, butter, etc. It’s not low in reward.” But it is low reward in the sense that you’re cutting out a broad swath of foods, and an entire macronutrient, that the brain very much wants you to eat. Eating more of a particular category of rewarding food doesn’t completely make up for the fact that you’re cutting out a whole other category of rewarding food that you would avidly consume if you weren’t restricting yourself.

So things aren’t maximally bad. And hunter-gatherers enjoy their healthy diets just fine. And certainly there are things like steak and wine and so on which are traditionally “good food” without being hyperprocessed hyperpalatable junk food. But if you really enjoy a glass of Chardonnay, is that “food reward” in a sense that’s potentially dangerous? Is anything safe? What about mongongo nuts? Is there anywhere we can get them?

At least the consolation of things making a little more sense. One thing that always used to bother me was the so-called “ice cream diet” – that is, if you eat a 700-calorie ice cream sundae for breakfast, lunch, and dinner every day, that’ll be only 2100 calories – around the average person’s daily requirement, and low enough for many people to lose weight. Why wouldn’t you want to do that? The idea of junk food being inherently damaging – while it has a bit of Puritan feel to it – at least fits our intuitions on these sorts of things and gives us a first step towards reconciling the conventional wisdom and the calorie math.

Overall I strongly recommend The Hungry Brain for everything I talk about here and for some other good topics I didn’t even get to (stress, sleep, economics). I would also recommend Guyenet’s other writing, especially his debate with Dr. David Ludwig on the causes of obesity (Part 1, Part 2, Part 3. I also recommend the list of diet tips that Guyenet gives at the end of the book. I won’t give them all away here – he’s been nice enough to me that maybe I should repay him by not reprinting the entire text of his book online for free. But it’s similar to a lot of standard advice for healthy living, albeit with more interesting reasoning behind it. Did you know that exercise might help stabilize the lipostat? Or that protein might do the same? Also, one piece of advice you might not hear anywhere else – potatoes are apparently off-the-charts in terms of satiety factor and may be one of the single best things to diet on.

And speaking of good things to diet on…

(note that this next part is my own opinion, not taken from The Hungry Brain or endorsed by Stephan Guyenet)

Slate Star Codex’s first and most loyal sponsor is MealSquares, a “nutritionally complete” food product sort of like a whole-foods-based, protein-rich, solid version of Soylent (it looks and tastes basically like a scone). I’m having some trouble writing this paragraph, because I want to recommend them as potentially dovetailing with The Hungry Brain‘s philosophy of nutrition without using phrases that might make MealSquares Inc angry at me like “bland”, “low food reward”, or “not hyperpalatable”. I think the best I can come up with is “unlikely to injure your hypothalamus”. So, if you’re looking for an easy way to quit the junk food and try a low-variety diet that’s unlikely to injure your hypothalamus, I recommend MealSquares as worth a look.