food reward/palatability hypothesis

Catching up on lost time – the Ancestral Health Symposium, food reward, palatability, insulin signaling and carbohydrates… Part II(d)

November 23, 2011 by GT

When last I left off, the subject of discussion was the critical question about the food reward/palatability hypothesis of obesity: Can palatability and reward value of foods be disassociated from the metabolic and hormonal effects of the individual nutrients being consumed and, in particular, the sugar and refined grains that “hyper-rewarding” foods seem to invariably contain?

Let’s start with the experiment in humans that Dr. Stephan Guyenet of wholehealthsource.org finds such compelling support of the food reward hypothesis. This was work done by Ted Van Itallie and Sami Hashim back in the 1960s. (For an idea of the simplistic notions held by Dr. Hashim about obesity and its cause and prevention, I highly recommend this video here. I discuss Dr. Van Itallie’s critical role in shaping the current thinking about obesity — i.e., the mess we’re in today — in chapter 23 of Good Calories, Bad Calories.)

In his “Case for the Food Reward Hypothesis of Obesity, Part II” post, Dr. Guyenet argues that this experiment is important because it demonstrates what he considers one of several critical requirements for the validity of the food reward hypothesis: “Decreasing the reward/palatability of the diet should cause fat loss in animals and humans that carry excess fat.” Here’s what he says:

One of the most striking weight loss studies I’ve seen was conducted in 1965 and involved feeding a bland liquid diet through a dispensing straw (12). Lean and obese volunteers were instructed to eat as much of the liquid food as they wanted, but they were permitted no other food. While lean volunteers ate a normal amount of calories and maintained weight, obese volunteers dramatically reduced their spontaneous calorie intake and lost fat rapidly, with one man losing 200 lbs in 255 days without hunger. This is exactly what one would expect if unpalatable/unrewarding food lowered the biologically “defended” level of fat mass. Interestingly, the diet was high in sugar but was otherwise very low in palatability/reward value.

This was Dr. Guyenet’s second discussion of the tube-feeding paper. As he explained in an earlier post on this experiment, the total number of subjects was four: two lean and two obese. The two lean were kept on the feeding machine for 16 and 9 days. They didn’t bother to decrease caloric intake, and so their experiment ended then. The two obese subjects, however, curtailed intake dramatically, to 275 calories per day for the male volunteer and 144 for the female). The man stayed with the feeding machine for another 70 days and was then sent home with the formula and the instruction to drink only 400 calories a day. He kept this up for another half year until he had lost the 200 pounds. Says Dr. Guyenet (in “Food Reward: a Dominant Factor in Obesity, Part II”, his earlier post):

This machine-feeding regimen was nearly as close as one can get to a diet with no rewarding properties whatsoever. Although it contained carbohydrate and fat, it did not contain any flavor or texture to associate them with, and thus the reward value of the diet was minimized. As one would expect if food reward influences the body fat setpoint, lean volunteers maintained starting weight and a normal calorie intake, while their obese counterparts rapidly lost a massive amount of fat and reduced calorie intake dramatically without hunger. This suggests that obesity is not entirely due to a “broken” metabolism (although that may still contribute), but also at least in part to a heightened sensitivity to food reward in susceptible people. [The italics are mine.]

So immediately we have a problem, and it strikes me as near-fatal for the food reward hypothesis of obesity. In Dr. Guyenet’s first post on the experiment (the one immediately above), he says that the regimen “was nearly as close as one can get to a diet with no rewarding properties whatsoever…. It did not contain any flavor or texture to associate them with, and thus the reward value of the diet was minimized.” In his second post (the first of the two I quote, just to make life confusing), he notes that the diet was “high in sugar” although he tries to hold onto the food reward hypothesis by stating that it “was otherwise very low in palatability/reward value.”

This is why I asked Dr. Guyenet at the AHS whether the formula diet had sugar in it. If it did, then how could it be bland? And how could it have a low food reward value, which is, more or less, the whole point? It might have a lower food value than what the two obese subjects were eating prior to the experiment, but low?

As Hashim and Van Italie noted in a footnote in their 1965 paper, and as Dr. Guyenet notes in his blog, the formula used was Nutrament. This was a liquid diet formula that went on sale in 1960 (according to Wikipedia), and if the composition then was anything like the composition now, a significant portion of the carbohydrate calories came from sugar.

So was it non-rewarding? Hashim and Van Italie refer to it as “bland” and Guyenet assumes it was as well, hence his description of it as “otherwise very low in palatabily/reward value.” But it had to be sweet if it had significant sugar in it; and indeed in the modern incarnation of Nutrament, which may or may not be the same as the original, there are 47 grams in every 12-ounce serving. This happens to be more sugar than you’d find in a 12-ounce can of Coke.

Frankly, the stuff sounds awful, but low in reward value? Well, only if a Coke is, too, and certainly not if Dr. Guyenet includes “liquid calories, particularly sweetened beverages” among the low-hanging fruit of the food reward hypothesis, which he does.

In fact, the point of a diet formula like Nutrament is not just that it contains enough protein and other nutrients that people can thrive on, say, 400 or 800 calories-a-day of the stuff. But it also has to taste good, so that consumers will continue to buy it and drink it day in and day out, even after they’ve moved into the weight maintenance phase of their lives — i.e., for the rest of their lives. It’s an example from the 1960s of what Dr. Guyenet describes as “the goal of processed food manufacturers… to create a product that maximally reinforces purchase and consumption behaviors—food reward!”

We can try to get around this problem by suggesting that bland and sweet is just not high in food reward value, as Dr. Guyenet tries to do, but we’re going to resort to this kind of, well, blatant contradiction only because we want to salvage this experiment as support for the hypothesis. So this formula must have a low-food reward value because an obese subject consumed less of it and lost weight and because we believe that foods with high reward value cause people to gain weight. Now we’re back to circular-definition land, a place I would prefer to never visit.

Now, how about the idea that a “cafeteria” or “junk food” diet makes humans and animals fat, a concept that was pioneered by Anthony Sclafani. The assumption is that such a diet is fattening because there’s something about eating a variety of foods, mostly junk foods, that is so rewarding or at least so less bland than a plain chow diet that both humans and animals get fat eating it. Here’s how Dr. Guyenet describes it:

In this model, animals are allowed free access to standard chow and water while concurrently offered highly palatable, energy dense, unhealthy human foods ad libitum.

In other words, they’re given an unlimited amount of human junk food in addition to their whole food-based “standard chow.” In this particular paper, the junk foods included Froot Loops, Cocoa Puffs, peanut butter cookies, Reese’s Pieces, Hostess Blueberry MiniMuffins, Cheez-its, nacho cheese Doritos, hot dogs, cheese, wedding cake, pork rinds, pepperoni slices and other industrial delicacies. Rats exposed to this food almost completely ignored their healthier, more nutritious and less palatable chow, instead gorging on junk food and rapidly attaining an obese state.

Aside from Dr. Guyenet’s description of standard rat chow as “whole-food based,” my major problem with this (which is the same problem Ramirez et al had 20-odd years ago with the existing research then) is that this is an experiment that changes an unholy host of variables, and the results are evoked to make a point about one: food reward value.

One advantage I have in this nutrition business as an arguably ignorant journalist is that I actually get to interview the researchers who do the work. (Technically anyone could do this, but the researchers are certainly more likely to give their time to a journalist, ignorant or not, than to what one of my acquaintances in academia refers to as “just a person.”) I interviewed Sclafani back on January 30, 2003 for GC,BC, and the interview revealed the obvious problem with this interpretation. As Sclafani told me, they started their cafeteria diet (which he was calling the “supermarket” diet at the time) with a variety of different foods (not quite as wide a variety as Dr. Guyenet is discussing above, but wide nonetheless): chocolate chip cookies, salami, cheese, bananas, marshmallows, milk chocolate, peanut butter and sweetened condensed milk, and then they later simplified it to four foods because the rats didn’t eat all the foods they gave them.

Which foods did they ignore? Sclafani said they never did a systematic study, nor had anyone else, as far as he knew (as of January 2003), but cheese, salami and peanut butter—the foods highest in fat and lowest in refined grains and sugar—seemed to be the foods they avoided in favor of the sweeter, starchy options. So the obvious question: are refined grains and/or sugar necessary to impart not just reward value, but reward value that leads to people and animals getting fat?

In fact, Sclafani told me that they had based their selection of foods on a hunch about what rats preferentially like, and so that’s why they included cheese in the list. It seemed like an obvious choice. After all, don’t you stick cheese in mouse traps when you want to rid your house of mice? And yet, cheese was not among the foods the Sclafani’s rats preferentially ate when given all these other refined carbs and sugary foods to eat instead. Maybe because the cheese was unrewarding. Or maybe because it was relatively if not completely refined-carb and sugar free, as were the salami and peanut butter.

This inability to differentiate food reward and/or palatability from the presence of refined carbs and sugars haunts virtually every example of the studies cited to document food reward and/or palatability.

Another example, not one used by Dr. Guyenet, is Kelly Brownell’s Yale Food Addiction Scale . This scale attempts to identify people who suffer from addiction to certain foods. The scale is based on a survey that gives a series of statements about eating habits. Subjects must say how true each statement is, on a scale from “never” to “four or more times or daily.” This goes along with a list of foods of which food addicted subjects might have “difficulty controlling their intake.” Here are the first four statements to give you an idea of what Brownell is getting at:

I find that when I start eating certain foods, I end up eating much more than planned.
I find myself continuing to consume certain foods even though I am no longer hungry.
I eat to the point where I feel physically ill.
Not eating certain types of food or cutting down on certain type of food is something I worry about.

So let’s assume, for the sake of argument at least, that the “certain foods” that illicit addictive behavior is very similar to the list of hyper-rewarding foods, the ones most likely to cause obesity. Here’s Brownell’s list of the foods that are most likely to be addictive:

–       Sweets like ice cream, chocolate, doughnuts, cookies, cake, candy, ice cream [yes, ice cream is listed twice.]

–       Starches like white bread, rolls, pasta, and rice

–       Salty snacks like chips, pretzels, and crackers

–       Fatty foods like steak, bacon, hamburgers, cheeseburgers, pizza, and French fries

–       Sugary drinks like soda pop

With the exception of steak and bacon, all of these foods are high in carbohydrates — refined or otherwise (the French Fries) — and/or sugars, even the foods defined as “fatty” with the aforesaid exceptions. If these foods are addictive and if they cause obesity, is it because they’re addictive or is it because of the metabolic and hormonal effects of consuming them — their effects on insulin signalling? There’s no way to tell without an exceedingly well-controlled and well-conceived experiment, but you can guess where my vote lies.

What about the steak and bacon, then? Well, if you ate nothing but those—steak and bacon every day, plus, say, the hamburgers or cheeseburgers without the refined grains attached, i.e., the buns—you’d be eating a weight loss diet (a ketogenic diet) and would almost assuredly lose weight doing it. So whether or not you consider steak and bacon addictive, it’s unlikely that they could be defined as foods high in reward value because they would tend to refute the hypothesis that high food reward value causes obesity. And now we’d be back to this problem of having to differentiate between hyper-rewarding foods or at least addictive foods that come with refined/easily digestible carbohydrates and sugars and cause fat accumulation and hyper-rewarding foods that don’t, and well, don’t.

Of the examples I could find in Dr. Guyenet’s discussions of the food reward/palatability hypothesis that held the promise of differentiating food reward value from underlying metabolic effects of the foods themselves (and the presence of refined or easily-digestible carbs and sugars), none of them actually came through with meaningful evidence.

The studies most likely to offer such a differentiation were those mentioned by Dr. Guyenet in his post, “The Case for the Food Reward Hypothesis of Obesity, Part II.” These were the studies evoked as evidence for the hypothesis because they demonstrate that “Individual sensitivity to food reward should predict future fat gain.” About this evidence he says:

I’m aware of three studies that have investigated this question. In the first, researchers found that the reinforcing value of food relative to a non-food stimulus predicted fat gain over the next year in 7-10 year old children (19). In the second, the responsiveness of reward-related brain regions to imagining palatable vs. unpalatable foods (as assessed using fMRI) predicted body mass index (BMI) gains in adolescent girls, and this effect was modified by gene polymorphisms in dopamine receptor genes (20). The third study also used fMRI to demonstrate that greater activation in reward-related brain regions during exposure to appetizing food cues predicted greater BMI gains over time in adolescent girls (21).

But of those three studies, none of them define what the high reward foods were, which foods were considered palatable and which were unpalatable. For all we know, the palatable foods were the ones rich with refined grains and sugars and the reason reward-related regions of our brain light up when we eat them (or at least when obese people do) is because our brains are responding to what these foods do to our bodies.

Reference 19 doesn’t specify at all which foods are actually high in reward value, nor do references 20 and 21, which are both by the same authors. They do, however, include a “cheeseburger” as an example of a processed food, demonstrating a certain bias against cheeseburgers that may be misplaced.

And reference 21 says that while BMI may have been related to the extent of activation in reward-related brain regions, as Dr. Guyenet points out, this was true regardless of whether the food being imagined was rewarding or palatable or not. Or the authors put it, “BMI [body mass index] was positively correlated with behavioral response to both appetizing and unappetizing food images, implying that food cues in general trigger greater attention in overweight vs. lean individuals.”

One obvious interpretation is that overweight individuals are hungrier than lean individuals, and so they have a greater response to any food in their reward centers. And, in fact, one point Dr. Guyenet’s mentor, Michael Schwartz, made of interest in his 2006 review in Nature “Central nervous system control of food intake and body weight” was that “food deprivation strongly augments the reward value… reduced food availability seems to exert a global, stimulatory effect on reward perception.” And so maybe the greater the BMI, the more likely the subjects were hungry or food deprived—a phenomenon I discuss at length in GC,BC— a state that could be due to increased insulin secretion and chronic hyperinsulinemia. And maybe refined grains and sugars augment reward value because they cause us to secrete more insulin and store calories away as fat and glycogen and make us hungry.

In GC,BC I quote Mark Friedman commenting on this potential carbs-insulin-hunger connection regarding just the cephalic phase of insulin secretion, the one that comes just by thinking about a particular food:

This cephalic release of insulin also serves to clear the circulation of “essentially anything an animal or a person can use for fuel. Not just blood sugar, but fatty acids, as well. All those nutrients just go away.” Hence, the thought of eating makes us hungry, because the insulin secreted in response depletes the bloodstream of the fuel that the peripheral tissues and organs need to survive.

And if this happens more in individuals who are insulin resistant, as most obese individuals are, we’re now back at a hypothesis that maybe the insulin signaling in the body is running the brain’s response, not vice versa. Yes, it’s the brain that’s stimulating the insulin secretion when we think about food, but what makes us hungry and makes the food then seem so rewarding is the effect of the insulin secreted in the body.

Catching up on lost time – the Ancestral Health Symposium, food reward, palatability, insulin signaling and carbohydrates… Part II(c)

November 18, 2011 by GT

We’ve been discussing the food reward/palatability hypothesis of obesity and whether this idea adds anything meaningful to our understanding of obesity. Is the evidence for it sufficiently compelling that we should cease to pay attention to the fact that insulin, as Yalow and Berson noted in 1965, is “the principal regulator of fat metabolism?”

One point I’ve been making in my posts and in my books is that it’s possible to find evidence in favor of virtually any idea – including the Flying Spaghetti Monster as the ruling force in the universe. More important to the validation of an idea or a hypothesis is the strength of the evidence that seems to refute it. Can the hypothesis survive more or less intact our best attempts to refute it?

This is one of the points I was trying to get across at the Ancestral Health Symposium: that the foods we eat today during our current obesity epidemic might have a high reward value, and that diets consumed by lean populations in faraway locales might not, isn’t particularly interesting. Yes, it supports the hypothesis, but how do we explain epidemics of obesity in populations that eat diets that don’t appear to have a high reward value? Do we need an entirely different hypothesis for them? That would be unfortunate.

“Here’s the fundamental concept that I think explains a lot of obesity in industrialized nations,” writes Dr. Stephen Guyenet of wholehealthsource.org .

We live in a more or less Darwinian economic framework (capitalism). Food manufacturers are in constant competition, and any food that sells poorly will rapidly disappear from stores. How do you get people to buy your product? You produce something that causes them to come back and buy it again. In other words, the goal of processed food manufacturers is to create a product that maximally reinforces purchase and consumption behaviors – food reward! If the product is not extremely rewarding, it won’t sell because it’s competing against other products that are extremely rewarding. Only the most rewarding products survive.

This certainly sounds reasonable, but don’t we also want a hypothesis of obesity that explains obesity rates in populations that lack such highly evolved food industries – obesity in non-industrialized nations? This would be a hypothesis that explains obesity-ridden populations in which the local industry isn’t quite so diligent in increasing food reward, if there are food manufacturers to speak of at all?

This is the question I asked in chapter one of Why We Get Fat. It’s why I listed a host of populations in which levels of obesity were reported, in some cases, approaching or exceeding those in the U.S. today, and yet with none of this Darwinian competition between food manufacturers, none of this extremely rewarding food (or at least not extremely-rewarding as we would define it today).

These populations included the Pima in 1902, the Sioux on the Crow Creek Reservation in 1928, the citizens of Naples in the years of extreme poverty following the Second World War and African-Americans in Charleston South Carolina in 1959. They included Zulu in Durban South Africa in 1960, and the citizens of Nauru in the South Pacific in 1961 — “By European standards,” a local physician wrote, “everyone past puberty is grossly overweight.” They included Trinidadians in the early 1960s and Chilean factory workers. They included urban Bantu pensioners “the most indigent of elderly Bantu,” in Johannesburg, South Africa in 1965, and so on.

What these populations had in common was varying degrees of poverty — from very poor to unimaginably poor — and the absence of a Darwinian food industry as Dr. Guyenet and others would describe it. They did have sugar and refined grains, but don’t we want a hypothesis of food reward that can make a claim more meaningful than “rewarding (or hyper-rewarding) foods are foods with sugar and/or refined grains in them?” (And if this ultimately is our definition, as I’ll discuss shortly, then we should be able to establish whether the reason they’re rewarding is or is not due to the peripheral effects of these foods, rather than their ability to influence brain chemistry, set point, etc.)

We also want a concept (or at least I do) that explains how we can have populations in which obesity and malnutrition and under-nutrition co-exist — for example, obese mothers with starving children, a common observation now in the literature.

Take Jamaica, for instance, where the British-trained diabetologist Rolf Richards, as I have quoted in Why We Get Fat and in my lectures, discussed the situation in 1973:

It is difficult to explain the high frequency of obesity seen in a relatively impecunious [very poor] society such as exists in the West Indies, when compared to the standard of living enjoyed in the more developed countries. Malnutrition and subnutrition are common disorders in the first two years of life in these areas, and account for almost 25 per cent of all admissions to pediatric wards in Jamaica. Subnutrition continues in early childhood to the early teens. Obesity begins to manifest itself in the female population from the 25th year of life and reaches enormous proportions from 30 onwards.

Now if we blame the mother’s obesity on the hyper-rewarding nature of the food she’s eating, we have to ask why these foods are rewarding only to the women and not to their children. The children aren’t fat, after all (not yet, anyway). In fact they’re starving. They’re under-nourished. We also have to explain why these foods only become rewarding from “the 25^th year of life” onward? And, perhaps most important, we have to explain why these women don’t fight the hyper-rewarding nature of these foods and remain lean.

After all, the food reward/palatability hypothesis of obesity, as we discussed in the first post on the subject, dictates that these foods cause neurochemical changes in the brain, which then raises the adiposity set point, thus making us eat more and get fat. Put simply, raising the set point in the brain makes us hungry or at least hungrier. Okay, so if this is right, then we can assume that the reward value of the food eaten in Jamaica made these women hungrier; they ate more, they got fatter. But why couldn’t they control their impulses and remain lean? Why couldn’t they experience the semi-starvation—or at least the perception of not having enough to eat—rather than their children who are indeed semi-starved?

Rather than giving in to the urge, consuming the superfluous calories themselves, and getting fat, why didn’t these mothers fight the urge and give those excess calories to their starving kids? If one of them has to go hungry or at least feel hungry, evolution, it seems, would always favor the mother doing it rather than the child.

We can try to rescue the food reward/palatability hypothesis of obesity in a case like this by simply making the claim that if these people are fat, then obviously something about their food must have been hyper-rewarding. (Something other than the refined carbs and sugars, as we’ll discuss in the next post.) But now our definition is becoming circular: The women get fat because of the hyper-rewarding nature of the food they’re eating, and we know that the food is hyper-rewarding because they’re fat. We just have to find or identify the particular foods in their diet that are the hyper-rewarding ones, and, as I said, it would be nice if they weren’t just sugar and refined carbs.

In his blogs, Dr. Guyenet suggests that home cooked food has a lower food reward value than processed, restaurant-produced fast food. This is one reason why, he suggests, populations like the Ache of Paraguay, the !Kung San, Polynesians and Melanesians (not counting those on Nauru and other islands that were obese) were lean: They “cooked their food in earth ovens and used no flavorings or salt .“

That we don’t cook our foods by these simple, spice-free, salt-free methods is offered as another explanation for the current obesity epidemic — “the shift from simpler home-cooked food to professionally engineered/processed food designed to maximize palatability and reward.” And this is also an explanation often offered for why carbohydrate restriction and paleo diets (not necessarily two different things) are weight loss diets. It’s not that they’re simply absent refined grains and sugars, as they are, but that the meats, fish, fowl, vegetables, and maybe tubers consumed are home cooked and/or so relatively bland that somehow they are low in food reward value.

But we can be confident that these extremely poor populations with high levels of obesity were also getting by on simple home-cooked food. Without having had the opportunity to visit Trinidad in the early 1960s or the South Dakota Crow Creek Reservation in 1928, I’m going to assume with confidence that a large proportion of the population, if not all, were not frequenting fast food joints and buying hyper-rewarding candy bars and soft drinks. So why were they fat? Certainly the presence or absence of flavorless home cooking is not enough to explain it. Nor can we explain it by claiming that only the affluent were obese, as Dr. Guyenet suggests, because these populations were anything but affluent.

So why were they fat? A familiar question.

Well, maybe it’s the low-hanging fruit of food reward—the refined grains and sugars? Populations that got fat ate significant quantities—particularly, the sugar—and populations that didn’t, well, didn’t. And when obesity suddenly blossomed in populations, it was because sugar and refined grains were new additions to their diets. And so diets that work for weight loss and weight maintenance are those that restrict refined grains and sugars (and maybe easily digestible starchy vegetables, as well, or maybe not) and diets that don’t, well, don’t.

This is what I argued in my books, although I’m arguing that the problem is caused by the metabolic hormonal effects of these foods in the periphery, their effect primarily on insulin signaling and, ultimately, fat accumulation. And the reason we find these foods rewarding and palatable is because of these metabolic hormonal effects.

As I’ve suggested in prior posts, the kinds of observations that are meaningful in situations like this—two competing hypotheses/paradigms—are only those that can differentiate between the two competitors. Evidence or observations that can be explained equally well by either hypothesis might have rhetorical value—good in an argument, in the spur of the moment—but they don’t add much to the scientific question at hand: Which hypothesis/paradigm is the right one?

This is why the observation that the Ache, the !Kung San, the Polynesians and Kitavans and Masai are lean or were lean, for instance, doesn’t tell us anything of significance about which hypothesis is right: Their lack of excess adiposity might be a result of their bland, unrewarding diets or it might be because their diets lack or lacked any significant amount of refined grains and/or sugars.

And even if the foods or diets that are consumed by obese populations and individuals today in the U.S. and elsewhere do seem indisputably rewarding and palatable, we’re still left having to demonstrate that this palatability, this high food reward value, is not due to the nutritional composition of the diet and the peripheral effects of the nutrients—the metabolic and hormonal effects in the body.

This was a point made back in 1989 by Israel Ramirez, Michael Tordoff and Mark Friedman of the Monell Chemical Senses Center in Philadelphia in an article entitled “Dietary Hyperphagia and Obesity: What causes them?”(Friedman is one of the scientists whose thoughts on obesity and over-eating significantly shaped my own. I owe him a debt of gratitude. For those who want to read what I think may be the single most thoughtful article written on obesity and hunger in the post-WW2 era, I’d recommend Friedman’s article with Edward Stricker, The Physiological Psychology of Hunger: A Physiological Perspective.)

The Monell researchers were discussing only the concept of palatability, not the food reward value of a particular food. (The idea that food reward and palatability could be differentiated — that they weren’t precisely the same thing — hadn’t gotten much if any play up until then.) So the question was whether or not palatability (whether a food tastes good) could be legitimately disassociated from nutrient composition and peripheral effects of the food. As Ramirez et al said repeatedly in this article, researchers almost invariably assumed that a food could be defined as palatable if the animals (or humans) ate more of that food than some other food, but this was an inference and nothing more.

It was well known at the time (although it may have been forgotten since then), as I discussed in Good Calories, Bad Calories, that animals can be made to like one food more than another, and so eat more of the one than the other, by interventions that influenced their underlying physiologic/metabolic/hormonal states. Here’s how I illustrated this in GC,BC:

Throughout the first half of the twentieth century, a series of experimental observations, many of them from [Curt] Richter’s laboratory [at Johns Hopkins University], raised questions about what is meant by the concepts of hunger, thirst and palatability, and how they might reflect metabolic and physiological needs. For example, rats in which the adrenal glands are removed cannot retain salt and will die within two weeks on their usual diet from the consequences of salt depletion. If given a supply of salt in their cages, however, or given the choice of drinking salt water or pure water, they will chose to either eat or drink the salt and, by doing so, keep themselves alive indefinitely. These rats will develop a “taste” for salt that did not exist prior to the removal of their adrenal glands. Rats that have had their parathyroid glands removed will die within days of tetany, a disorder of calcium deficiency. If given the opportunity, however, they will drink a solution of calcium lactate rather than water—not the case with healthy rats—and will stay alive because of that choice. They will appear to like the calcium lactate more than water. And rats rendered diabetic voluntarily choose diets devoid of carbohydrates, consuming only protein and fat. “As a result,” Richter said, “they lost their symptoms of diabetes, i.e., their blood sugar fell to its normal level, they gained weight, ate less food and drank only normal amounts of water.

In short, change underlying physiologic/hormonal conditions and it will affect what an animal chooses to eat and so seems to like or find rewarding. The animal’s behavior and perceptions will change in response to a change in homeostasis – in the hormonal milieu of the cells in the body.

It’s quite possible that all those foods we seem to like, or even the ones we find rewarding but don’t particularly like, as Dr. Guyenet argues, and that subsequently cause obesity (not necessarily the same thing) are those foods that somehow satisfy an underlying metabolic and physiological demand. This in turn might induce our brains to register them as more palatable or rewarding, but the initial cause would be the effect in the periphery. The nutrient composition of the food, in this case, would be the key—what it’s doing in the body, not necessarily the brain.

Here’s how Ramirez, Tordoff and Friedman phrased this issue back in 1989:

In order to demonstrate that diet palatability per se causes hyperphagia [overeating or a voracious appetite], it must be shown that obesity-inducing foods are more palatable than control foods, this greater palatability is not merely a reflection of the postingestive [after entering the digestive tract] consequences of the foods, and altering palatability without altering nutritional composition can cause obesity. This has not been done.… Although various experiments have been cited as supporting the palatability hypothesis, they are not decisive because, in every case, palatability was confounded with changes in nutritional composition.

That an experiment is “not decisive” unless this is done is the critical point. If an experiment that ostensibly changes food reward makes an animal eat more of a particular food and/or get fatter, and it does so by changing nutritional composition—say, the foods that are defined as more rewarding have more sugar in them, or are more refined, or have a greater water or fat content—then the researchers have to demonstrate that it’s not the change in nutritional composition and post-ingestive effects of that change that is causing the overeating and obesity. An observation that one diet produces obesity compared to another because it’s ostensibly more rewarding or palatable has to do the same. Otherwise either hypothesis could be true, and we haven’t learned anything.

Take the idea, as Dr. Guyenet suggests, that people will eat more at a sitting if foods are palatable than if they’re not, which seems kind of obvious. The better a food tastes, the more likely we are to eat more of it. But then Dr. Guyenet adds that this is true even of foods with “little or no nutritional quality.” This is how he phrases it in a recent post:

Many human studies have shown that people eat more food at a sitting if the food is higher palatability than if it is lower palatability (11). This is true even if palatability is manipulated using substances that have little or no impact on the nutritional quality of the food, including saccharin (sweet), monosodium glutamate (savory) and herbs/spices.

The reference is a review article that actually makes the point that the evidence is ambiguous on the eating more issue when the foods have little or no nutritional quality. “Several studies showed no effect of sweet taste on either hunger ratings or food intake,” the authors write, “when the sweetener was provided in the form of gelatine, corn flakes or fromage blanc or as aspartame- or saccharin-sweetened drinks.” In fact, the authors then go on to suggest this is true of all “sweet taste” whether from caloric sweeteners or non-caloric, which doesn’t seem to do my hypothesis any favors either.

But what I’m arguing is that the key isn’t whether people eat more, but whether the foods stimulate fat accumulation. And if they do make us fatter, how?

The food reward hypothesis suggests that it happens because of the effect of the sweet taste in the brain, not in the body. If the former, then sugar and saccharine might be expected to be equally fattening, so long as we consider sugar and saccharine-sweetened beverages to have equal reward value or to be considered equally palatable by humans.

If the reward value is not the critical factor, then it’s a reasonable assumption that sugar-sweetened beverages will be more fattening than saccharine or aspartame-sweetened beverages. And we could do a clinical trial and see which turns out to be true, although we can also guess what we think such a trial (randomized, well-controlled) would find. Not surprisingly, I’d vote for the sugar-sweetened beverages being more fattening.

This doesn’t mean, by the way, that artificially-sweetened beverages could be absolved of having any fattening properties because we might still secrete insulin in response to these beverages. They may fool us into thinking that they have carbohydrate or sugar calories in them. And this insulin secretion could be cephalic — a kind of Pavlovian response — which would mean that the brain is telling the pancreas to secrete insulin (via the vagus nerve). But it would now be doing so not because the food is rewarding necessarily, but because the body has come to associate sweet taste with the presence of carbohydrates and feedback loops in the brain are working to get the body ready by secreting insulin.

In my next post, I’ll discuss more of the evidence offered in support of the food reward/palatability hypothesis and ask the question that Ramirez et al did: are palatability and food reward confounded with changes in nutritional composition, and if so, what might that confounding be?

Catching up on lost time – the Ancestral Health Symposium, food reward, palatability, insulin signaling and carbohydrates… Part II(b)

November 14, 2011 by GT

When last we left off, the subject was the food reward/palatability hypothesis of obesity and why I find it so unconvincing and problematic.

This post is going to address that issue by first discussing three new papers published on the subject of sugar. Then I’m going to ask a lot of questions, hoping at least some of the answers will be obvious. All three papers are from Peter Havel and his collaborators at U.C. Davis and Vanderbilt; all three looked at the metabolic effect of the fructose-component of sugar, while one of them one also looked at the effect of sugar itself in the form of high fructose corn syrup (HFCS).

Paper number one describes an experiment in which rhesus monkeys were fed their usual monkey chow diet supplemented by a daily 300-calorie ration of fructose-sweetened water. After a year, every last one of the 29 monkeys had developed “insulin resistance and many features of metabolic syndrome, including central obesity, dyslipidemia and inflammation.” Four of the monkeys progressed to type 2 diabetes.

Worth noting is that the monkeys apparently drank all the fructose-sweetened drinks they were given, but they adjusted for the 300 additional calories by cutting back significantly on the chow. All in all, they averaged only 26 calories per day more with the fructose than they did without it. This suggests that the negative sequelae observed over the course of the year were indeed caused by the fructose itself and not an increased intake of total calories (unless we’re willing to accept that increasing calories by just a couple a dozen a day is sufficient to do some very bad things to monkeys and do them relatively quickly.)

The second and third papers, both published in October, were randomized controlled trials in humans — rather than primates or rodents — which is always a nice attraction in nutrition research since there’s no guarantee any animal model really reflects the physiological situation in, well, us.

The second paper reported that overweight and obese older adults (40 to 72 years-old) getting a quarter of their calories from fructose-sweetened beverages used less fat for fuel and actually expended less energy than did the same subjects when they were getting the equivalent calories from glucose drinks. So the calories were the same; the metabolic effects were different. For the fructose, the effects were what we’d expect (okay, what I’d expect) if the fructose beverages were causing or exacerbating insulin resistance, an observation that Havel et al had published earlier. The more insulin resistant these people became, the less fat they used for fuel—hence, we can assume, the more fat they stored—and the lower their basal metabolic rate. (The rhesus monkeys, too, had decreased their energy expenditure in response to drinking fructose.)

The third study was a trial in younger subjects (18 to 40-year-olds), some lean, some not. These subjects were given three beverages to drink every day, constituting again about a quarter of their day’s ration of calories. The beverages were sweetened either with fructose, glucose or high fructose corn syrup. For the HFCS group, this 25 percent of calories was compatible with what the U.S. Dietary Guidelines considers a safe upper limit for sugar consumption. Still, after only 12 days—less than two weeks—subjects in both the HFCS and fructose groups, but not the glucose group, saw a significant increase in heart disease risk. Triglycerides went up; LDL cholesterol went up, and ApoB concentrations, a measure of the number of LDL particles, increased.

What can we take away from these studies? Well, these three papers certainly support the contention that the sugars consumed in western diets have very specific deleterious metabolic effects, and that maybe these sugars are the, or at least a proximate cause of insulin resistance and metabolic syndrome, and so, we can assume, obesity and type 2 diabetes and perhaps all the other chronic diseases that associate with these two conditions (cancer anyone?). This was the thesis of my April New York Times Magazine cover article “Is Sugar Toxic.” Here’s how Havel et al phrased this notion in the monkey paper:

The incidence and prevalence of insulin resistance and metabolic syndrome in the United States has increased dramatically over the past several years, and we and others have proposed that this increase may in part be attributable to increased consumption of fructose derived from dietary sugars, principally sucrose and high-fructose corn syrup (HFCS).

And, yes, the three papers certainly add fuel to this possible fire.

So on one hand, we can explain the metabolic abnormalities observed in these three studies—the insulin resistance, metabolic syndrome, raised triglycerides and increases in ApoB and LDL cholesterol—as all caused by the metabolism of the fructose in the liver in concert perhaps with the insulin-stimulating effects of glucose. This is not a particularly controversial position. The sugar industry is not a fan, but research has consistently demonstrated these effects and has since the 1960s, and the biochemistry behind them is well understood.

So now we have three clear propositions and we’ll follow them up with the obvious question:

Proposition #1: The metabolism of fructose in large quantities by the liver results in a system-wide hormonal disruption — insulin resistance, in particular.

Proposition #2: Insulin resistance is intimately associated with obesity and is the underlying defect in type 2 diabetes.

Proposition #3: Insulin is the fundamental hormonal regulator of fat accumulation in fat cells.

Obvious question: Considering these three propositions, isn’t it likely that insulin resistance and the chronically elevated levels of insulin that go with it are causal factors in the obesity seen in the monkeys and, well, in humans who consume significant sugar, too?

This line of reasoning is one of the principle reasons that I’ve argued in my books and this blog that the carb/insulin hypothesis should be considered the null hypothesis of obesity, the one we believe until remarkable, unambiguous evidence comes along to refute it.

We have a disorder, obesity, that associates with a host of chronic diseases of western diets, all of which are associated as well with metabolic syndrome – i.e., insulin resistance — and type 2 diabetes. So if insulin plays a major role in regulating fat accumulation in individual fat cells, which is not a point of controversy, and if dysregulation of insulin signaling is a major component if not the causal factor in the diseases that associate with obesity, also not particularly controversial, it seems like a very good assumption that obesity, too, is caused by a the same dysregulation in insulin signaling.

Now the salient questions are these: How remarkable and unambiguous does the evidence have to be before we toss all this out in favor of the idea that we get fat because rewarding foods stimulate neurochemical changes in brain centers that raise our adiposity set point and ultimately make us eat more than we expend? And what do we gain by doing it?

I will argue that tossing out the role of insulin on fat accumulation to embrace the idea that rewarding foods stimulate brain centers seems inherently foolish, because the evidence is by no means unambiguous and in the process we disassociate weight gain from all these other insulin-mediated and very closely related disorders.

Let’s first try to address this cost-benefit ratio — what we gain from the food reward/palatability hypothesis compared to what we lose — by narrowing our scope to the three sugar papers from Havel’s group. We want to answer these two questions: 1). what does the food reward/palatability hypothesis of obesity add to our understanding of the fructose-related effects documented in these papers? 2). Is it a valuable addition?

As I said, few of us, if any, would doubt that sugar-sweetened beverages (SSBs, as they’re now fashionably known) or fructose-sweetened beverages have a high-food reward value. The monkeys seemed content to drink all their 300 calories-a-day of fructose, and to do so at the expense of other more nourishing food (the chow). Put simply, they apparently found the fructose more rewarding. Havel told me when I interviewed him for the NYT Magazine article that they had difficulty finding any of the younger (human) subjects for their experiments who didn’t already drink at least two daily sugar-sweetened beverages, and quite a few were drinking six.

So it’s certainly a reasonable assumption that SSBs are hyper-rewarding, among the low-hanging fruit in the food reward/palatability world, as , as Dr. Guyenet of Whole Health Source has categorized them in his posts on this subject. Easy targets in other words—indisputably rewarding.

Now these highly rewarding beverages are given in a randomized-controlled trial to human subjects, as Havel and colleagues did, and the amount given is fixed. They’re given daily to monkeys as part of their dietary regimen, as Havel and colleagues did, again a fixed amount. In both species, they cause the metabolic/hormonal effects we would expect on the basis of a few decades of biochemical and endocrinological research on insulin and on the metabolism of fructose in the liver.

So now we’re going to take a leap of faith and assume that the hyper-rewarding nature of these beverages explains why the monkeys got fatter drinking them, and maybe the humans, too, if any of them did indeed gain fat in such a short period on the beverages, but what about the metabolic and hormonal effects observed? Does the fact that SSBs have a high food reward/palatability value tell us anything meaningful about why these sugar- or fructose-sweetened beverages cause peripheral effects in addition to increased adiposity—insulin resistance, metabolic syndrome, type 2 diabetes, raised triglycerides and ApoB number, etc.?

Here’s another way to phrase that same question: If consuming these different sugar waters have very well-specified effects in the body (peripheral effects, as they’re known in the lingo), and these effects are sufficient to explain all the observations – increases in adiposity, insulin resistance, dyslipidemia, type 2 diabetes, etc. — why evoke a couple of arguably vague concepts like food reward and palatability to explain one of them alone, the increase in adiposity?

Let’s agree for the moment, that it’s worth it. We’re going to accept this hypothesis because it’s just right and the carbohydrate/insulin hypothesis is not. It’s the hyper-rewarding nature of sugar- and fructose-sweetened beverages causes fat accumulation, as seen in the monkeys in paper number one, and in free-living humans drinking SSBs. If we decide this reward value thing is at least a major contributor, we’re still stuck with having to explain the metabolic and hormonal disorders. We can’t just ignore those, so we have to complicate the hypothesis to do so — add epicycles, as historians or philosophers of science would put it. We have to explain how these SSBs also cause insulin resistance and metabolic syndrome, why they raise triglycerides and LDL cholesterol and ApoB etc..

Researchers who study obesity and insulin resistance have been confronted with this same problem since the early 1960s, once they decided that obesity had to be caused by taking in more calories than we expend. The way they’ve traditionally done it is to say that we get fatter because we take in more calories than we expend, and then we get insulin resistant because we are getting fatter. Two different mechanisms.

This rationale can help proponents of the food reward/palatability hypothesis out of the same hole. In this case, blame the excess fat accumulation on the hyper-rewarding nature of sugar and the neurochemical effects it induces in the brain; this raises set point and so we eat more than we did and get fatter. Then we can blame the insulin resistance and all that goes with it on the process of getting fatter.

Not too bad, but then we have to explain why the same metabolic effects happen in individuals who remain lean, who do not accumulate the offending fat, and we can’t, or at least not without adding yet another mechanism (another epicycle) for the lean people. Because lean people can also be insulin resistant and dyslipidemic and get type 2 diabetes and all the associated chronic diseases. So one way or the other (or so it seems to me), we need our knowledge of the peripheral effects of sugar consumption – the metabolic and hormonal effects in the liver, the pancreas and other organs – to understand at least some of the observations, if not all of them.

In its current form, the palatability/food reward hypothesis explains only fat accumulation. It explains why the monkeys gained weight, and I guess why we do too when we drink a lot of sugared beverages, but it offers no explanation for the the metabolic consequences that accompany the weight gain, both in the studies discussed and in real life.

Here’s yet another question to always keep in mind when thinking about the food reward/palatability hypothesis of obesity: Do we gain anything from it other than the obvious: that if these foods weren’t highly rewarding or palatable, we probably wouldn’t eat them, or at least not enough of them to make us fat and cause the deleterious metabolic effects?

And even if we do gain something meaningful from acknowledging that the food reward/palatability value of foods causes us to consume more of them, this benefit to our understanding would still come with a very important caveat: Maybe the reason these foods have a high reward value or are so palatable is because of the metabolic and hormonal effects of eating them. Maybe a food that can cause insulin resistance or hyperinsulinemia can also cause us, through its various peripheral effects, to crave it more, to find it more rewarding.

Anything’s possible, and this is one hypothesis, a very important one, we should always keep in mind. And it’s one I’ll return to shortly, or at least shortly by my standards—i.e., over a few more posts and several thousand words more words.

(And when I’m done with these food reward hypothesis posts, I’ll get to the evidence against the insulin hypothesis. Lord knows when that will be, but I’ll get there.)

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