2011 November

Catching up on lost time – the Ancestral Health Symposium, food reward, palatability, insulin signaling and carbohydrates… Part II(e, as in “end” and “enough already”)

November 25, 2011 229 Comments

In our last post, we discussed, among other things, an experiment from the 1960s that Dr. Stephan Guyenet of wholehealthsource.org has evoked to support the food reward/palatability hypothesis of obesity. This was an experiment by Sami Hashim and Ted Van Itallie published in 1965. Four subjects, two lean and two obese, consumed a formula diet from a machine that dispensed it through a tube. The lean subjects consumed as many calories as they always did and maintained their weight. The obese subjects responded by dramatically reducing their caloric intake – to 400 calories a day or less. The male subject continued this regimen for the better part of a year (although dispensing with the tube-feeding) and lost 200 pounds, half his body weight, doing so.

When I interviewed Dr. Van Itallie for GC,BC he considered this tube-feeding device to be his primary contribution to the field of obesity research. I would question whether this is a significant contribution to anything, but his experiments were interesting, nonetheless, and I’d like to take a little more space here to discuss them.

The questions we want to answer ultimately about this experiment are simple ones: why did the obese subjects consume so few calories on the feeding tube, and why was the one guy able to keep this up with the formula, eating 400 calories a day, lose so much weight, and do so without apparently being particularly hungry. Dr. Guyenet evokes the low food reward value of the formula to explain this (nonsensical as it seems when the formula itself, as discussed in the last post, was loaded with sugar). But do we need the food reward/palatability hypothesis to explain this particular n=1 anecdotal observation about extreme weight loss?

One flaw I find in Dr. Guyenet’s interpretation of this experiment may have to do with the fact that he’s a laboratory researcher not a clinician working with human subjects or patients. As such, it may be hard for him to imagine all the various ways that humans will screw up an experiment, ideal as they might be otherwise as the experimental subject of interest.

One obvious problem with any such study like Hashim and Van Itallie’s – non-randomized, only a few subjects (4 in this case) – is that there are an almost infinite number of reasons to explain what they observed. Here’s Hashim and Van Itallie mulling this issue themselves:

Whether the inhibition of food intake exhibited by obese patients represents a physiologic effect of massive stores of fat, or whether it results from psychologic factors relating to guilt about the obesity, fear of the feeding device, inability to adjust to the formula, or some other cause, is unknown. The fact that such a striking difference does seem to be present merits further investigation.

Oddly enough, Hashim and Van Itallie neglect the most obvious explanation for what they witnessed, and I suspect it’s because they, too, had little experience until then with obesity research on human subjects. Maybe their two obese subjects reduced their food intake so dramatically because they had reason to do so. They wanted to lose weight and had significant excess weight to lose. The lean individuals didn’t, and so they didn’t bother to reduce their intake. That simple. The obese man, for instance, was pathologically obese – 400 pounds – and he volunteered for the experiment. So maybe he was using this as an opportunity to lose weight, consciously or unconsciously. Why else volunteer?

This is a very common problem with experiments that use obese or overweight human subjects and effectively any kind of diet or lifestyle intervention. People who are overweight have a motivation to lose weight. We could argue that the fatter they are, the greater their motivation. Even if they’re instructed specifically not to eat less, for instance, because the researcher want to study the efficacy of exercise or of ad libitum eating on, say, a low-fat or low-carb diet, the researchers can never be sure that the subjects didn’t ignore their instructions because, well, they want to lose weight and they’re in the kind of institutional setting that will help motivate them.

When I was researching GC,BC, quite a few obesity researchers made note of this problem. You could give obese subjects virtually any dietary or lifestyle instructions in an institutional setting, I was told, and they’ll promptly lose at least a little weight, because they want to lose weight. That’s why they’re there; that’s why they volunteered. And they are likely to eat less (calories and/or carbs or fat) no matter what instructions they get. That’s why when you do studies with obese subjects you randomize them into two or more arms and try to make sure that each arm has an equal intervention – a diet or lifestyle change that requires an equal amount of counseling and effort to get right. This should do a pretty good job of dealing with this motivation confounder, although you can never be sure.

In 1971 Hashim and Van Itallie returned to their food dispensing machine experiments in a paper in the New England Journal of Medicine. This time they reported that female obese subjects consumed less and lost weight on the tube-fed formula diet, while male lean subjects did neither. The NEJM published a letter in response, by a Virginia physician, making this precise point:

“All that one has to postulate to explain the differences in the behavior of the two groups is that the male group was at acceptable weight, and knew it, and that the other group was obese, and knew it, and that the obese females were trying to lose weight and did so by the very simple expedient of reducing the volume of food intake.”

In their response to the letter, Hashim and Van Itallie argued that this was unlikely to be the case based on the fact that all the obese subjects, men and women, behaved the same way: “It overstrains credulity to interpret such uniform behavior as being entirely the product of a systematic attempt to lose weight.” Well, not my credulity, but it’s open to investigation. In a real science, Hashim and Van Itallie would have tried to figure out a way to rigorously test the hypothesis, not leave it up to us to judge whether their defense was adequate.

(That van Itallie and Hashim defended their decision to compare male lean subjects with female obese subjects on the basis that this was the best they could do – “Unfortunately, our choice of subjects was limited; thus, this `fault’ in design was thrust upon us,” they say– boggles the mind. It may be all you need to know to understand why I consider most obesity research to border on pseudoscience. And this, in a paper published in what’s considered to be one of the two best medical journals in the world. Sigh.)

Okay, so we still haven’t answered the question of why even one obese subject – male or female – would be able to maintain a 400 calorie-a-day regimen of this formula for months and lose significant weight without apparent hunger. Is it because the formula has a low-food reward value (sugar or not) or because, well, it lowers insulin levels and so this man is happily consuming his own fat, just as if he was on a protein-sparing modified fast (as many as 600 or 800 calories a day, but no carbohydrates) or starving himself entirely, or even, perhaps, eating an ad libidum ketogenic diet of virtually all protein and fat, in which hunger is also apparently suppressed in association with weight loss?

This brings us back to the question of calories vs. carbohydrates and why diets work when they do, as I discussed in this post. And it always discourages me when this issue is missed by otherwise intelligent commentators like Dr. Guyenet.

Here’s the composition of the formula, according to Dr. Guyenet: “carbohydrate supplied 50 percent of the calories, protein 20 per cent and fat 30 percent.” So, regardless of the food reward value, the 400-pound subject was eating a diet of roughly 200 calories a day of carbohydrates. Hashim and Van Italie tell us that he was eating about 3000 calories a day prior to going on the feeding tube, and if his pre-experiment diet was half carbs, than our subject cut his carbohydrate consumption on the feeding tube from 1500 calories a day or so down to 200.

Two hundred calories of carbohydrates – 50 grams worth – was low enough to be ketogenic. “Ketonuria was always present,” Hashim and Van Itallie write, “ and the blood ketone levels on several occasions was 15 mg. per 100 ml.” This means insulin levels on the diet were extremely low, despite the 50 percent carbs.

Why wouldn’t he be hungry? Well, here’s a guy who lost 200 pounds in 265 days. Assuming three quarters of that weight loss is fat and the rest lean tissue, that’s 150 pounds of fat that he burnt in 265 days, and this was fat he wasn’t burning back when he was weight stable and eating 3000 calories a day to run his body. That’s an average of about 1980 calories of his own fat he was consuming every day. The calculation is simple:

150 pounds of fat x 3500 kcal per pound of fat/265 days = 1981 kcal/day

Add to this the fifth of a pound or so of lean tissue he’s also consuming daily (50 pounds of lean tissue/265 days), and we can easily add another few hundred calories a day from the protein. So the fact that he could reduce his food consumption from 3000 calories a day down to 400 without feeling hunger, is not something that requires a lot of extra thought if we realize that in doing so, and lowering his insulin levels, he was consuming far more than 2000 calories a day of his own body – fat and protein — to make up the difference. We don’t have to evoke somewhat vague properties about the hyper-rewarding nature of the food to explain this.

There’s one other aspect of Hashim and Van Itallie’s crazy exercise in dispensing formula diets from a tube that I find relevant. The goal of the experiment they published in the New England Journal of Medicine in 1971 was to examine whether obese and lean subjects would respond to surreptitious changes in the nutrient density of the formula they were consuming. Hashim and Van Itallie diluted the formula with different amounts of water, fed it through the tube, and measured whether the subjects responded to the dilution by taking in more formula.

In this case, we can assume that the formula might indeed have been bland and so low in food reward value because Van Itallie and his researchers made it themselves without sugar. The carbohydrates in it were dextrose (glucose) and lactose.

Now the obese female subjects all “lost weight as long as they fed themselves by machine.” The lean males seemed to adjust to dilution of the diet by drinking more of it. Not so the obese women. They just kept drinking little of the stuff and losing weight, regardless of the dilution.

So if we buy into the food reward hypothesis (and we don’t buy the notion that the “obese females were trying to lose weight and did so by the very simple expedient of reducing the volume of food intake”), then we can conclude that non-rewarding food serves to lower the set-point of women and so they eat less and lose weight. All well and good, enormous assumption aside.

But Hashim and Van Italie also studied two obese adolescents under the same circumstances. The obese adolescents (boys, 13 and 15) ate as much as ever of the formula diet, although one of them actually refused to use the feeding machine after a week. Smart kid. One way or the other, “these two obese juvenile subjects differed from the adult subjects in that they either maintained or gained weight while receiving the machine-dispensing formula.”

Hmmmm…. Does this mean the reward value if a food is dependent on age? On sex? Men find bland formulas rewarding and get fat on them, women don’t? Or children do and adults don’t? Does it mean that Hashim and Van Italie’s food reward studies are so poorly controlled that, to steal a phrase, it overstrains credulity to consider any interpretation meaningful? My vote is with the latter, but once again I’m biased.

Filed Under: General

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

November 23, 2011 46 Comments

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.

Filed Under: Bad Science, Calories-in-Calories-out, Diets, food reward/palatability hypothesis, General, Glycemic Index, Obesity and weight regulation, Weightloss Diets

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

November 18, 2011 148 Comments

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?

Filed Under: Bad Science, Calories-in-Calories-out, Diets, food reward/palatability hypothesis, General, Obesity and weight regulation, Weightloss Diets

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

November 14, 2011 156 Comments

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.)

Filed Under: Calories-in-Calories-out, food reward/palatability hypothesis, General, Obesity and weight regulation

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

November 9, 2011 212 Comments

When last I posted, oh so long ago, I promised next to discuss the food reward/palatability hypothesis of obesity and why I find it so uncompelling and more than a little bit disheartening. Why, in effect, I think it is the kind of bad science that begs to be challenged, as I did, when it is presented in a public forum, as Dr. Stephan Guyenet of Whole Health Source did at the Ancestral Health Symposium back in August. This is the first of five posts to address this and I promise (really) that it will be days between posts, not months.

Here’s how Dr. Guyenet describes his hypothesis in his sixth of an increasing number of blog posts on food reward:

…The evidence as a whole shows that chronic consumption of foods with an excessive reward value causes abnormalities in parts of the brain that regulate body fatness, metabolism and reward/motivation. This can lead to weight gain and metabolic problems, and favor addictive and compulsive relationships to food and other things. The combination of readily accessible, cheap, high-reward food, and stressful lifestyles that drive us to eat it, is probably a major contributor to overweight, obesity, diabetes and perhaps other health problems in affluent nations.

What makes this hypothesis novel is that the ability of a particular food to make us fat — what makes a food fattening, in effect — is mediated, according to Dr. Guyenet, through its ability to stimulate neurochemical effects in the brain.

So why do I find this intriguing idea objectionable, so objectionable, in fact, that I was willing to stand up at the AHS and make a bit of spectacle of myself? Well, for starters, the food reward/palatability hypothesis can’t explain the kinds of observations about obesity and weight regulation that I’ve been arguing in my books must be explained by any viable hypothesis of why we get fat. This is the primary issue, obviously, as a hypothesis that can’t explain the necessary observations is a failed hypothesis. And we’ll get to this issue in the posts to come.

The lesser reason for my objections, and the subject of this post, is that this hypothesis seems to be yet another thinly-veiled variation on the energy balance paradigm of obesity — calories-in, calories-out — and I’ve been arguing that this particular paradigm is fatally misguided in a variety of different ways. I believe that obesity researchers will never make meaningful progress until they rid themselves of this belief system, and that so long as they hold onto it they’ll be effectively blaming the obese for the problem of their obesity. Hence, finding yet a new way to embrace it, or popularizing an old way, as Dr. Guyenet has, seems to be a step in precisely the wrong direction.

Ultimately, this comes down to what I consider the two competing obesity paradigms or belief systems.

Competing paradigms: 1. body rules

One is a body-rules paradigm and I’ve been arguing that it’s the only one that can do a reasonable job of explaining all the meaningful observations. Changes in the hormonal and enzymatic regulation of fat metabolism—in the regulation of fat storage and oxidation—drive changes in adiposity; and changes in adiposity drive compensatory changes in intake and expenditure.

Here, the body is running things. Indeed the organ in control may be the fat tissue itself in concert with the liver. The University of Vienna endocrinologist/geneticist Julius Bauer described this fat-rules concept back in 1929 by saying that the fat tissue of someone who’s obese (what he called “abnormal lipophilic tissue) “maintains its stock, and may increase it independent of the requirements of the organism. A sort of anarchy exists; the adipose tissue lives for itself and does not fit into the precisely regulated management of the whole organism.”

In this scenario, the brain plays no more role in regulating the growth of the fat tissue than it would regulating the growth of any tissue — a tumor, for instance, which is a metaphor that Bauer uses, or the growth of fat tissue in breasts and hips and butt when a young girl goes through puberty, or the fat put on by a mother-to-be when she is pregnant, another Bauer metaphor, or just the growth of lean and fat tissue in children as they develop and mature.

In all these cases, the body is doing its own thing, more or less independent of the brain’s input, even though the brain, in the case of growing children, is the source of the growth hormone that is driving the growth. More energy has to be taken in than expended while growth is occurring (at least by the tissue itself, if not the whole body), but that “positive energy balance” — calories in greater than calories out — is a compensatory effect of the growth; it’s not a cause. The brain does what it always does, which is reacting and modulating homeostasis in response to environmental signals. But it’s a secondary organ in this sense.

In this paradigm, specific foods are fattening because they induce metabolic and hormonal responses in the body — in the periphery, as its known in the lingo — that in turn induce fat cells to accumulate fat. The brain has little say in the matter. As I describe it in my books (and as it was described to me by the few researchers today who hold this view), we don’t get fat because we overeat; we overeat because we’re getting fat.

If we come to crave specific foods or find them more rewarding than others and these foods are fattening — not necessarily the same thing — then we likely do so because of their physiologic effects, the changes in the hormonal milieu of the body caused by the consumption of these foods. Foods that make us fat come to be foods we crave, because these foods are also the foods that make us hungry. So how much we might like a food or how rewarding we might find it or how much we might crave it are primarily consequences of the peripheral metabolic/hormonal effects.

In this paradigm, meals stimulate hormonal responses—insulin, in particular, either in the short term (glucose) or the long term (fructose)— and this in turn directly influences both the storage of fat and the oxidation of fatty acids elsewhere in the body. The balance of forces working on the fat tissue, a dynamic equilibrium, ultimately determines how much fat we accumulate. As fat accumulation increases, so does secretion of leptin and other adipokines that work in a variety of feedback loops in the brain and the body (as does insulin itself) to ideally prevent excessive fat accumulation.

This body-rules hypothesis, of course, isn’t the conventional wisdom. If it were, I would be doing something else with my career.

Competing paradigms: 2. brain rules

The conventional wisdom is that we get fat because we take in more calories than we expend. Simple enough. We get fat because we overeat, not the other way around. Changes in energy balance—calories-in minus calories-out—drive changes in adiposity, in how much fat we carry around in our fat cells.

Ultimately, as I discuss in Why We Get Fat, this is a brain-rules paradigm. After all, both the components of overeating — eating too much, aka gluttony, or moving too little, aka sloth — are both behaviors and in this paradigm behaviors are psychological phenomena not physiological.

Researchers who live in this paradigm are invariably trying to discover what’s wrong with our brains or the signaling to our brains that cause this particularly cherished organ (what Woody Allen memorably described as his “second favorite organ”) to screw up. Why can’t the brains of people who become obese or overweight get the energy balance thing right? Or why do these brains effectively desire more fat on the body than is healthy? Why do they set the “set point” of adiposity too high? The problem with people who get obese is in their brains, not their bodies (even though the excess fat is in the body).

In this paradigm, the fat tissue is more or less passively following the brain’s lead. Meals will stimulate a variety of gut hormones and fat-derived hormones like leptin, grhelin, etc., and these in turn signal the brain whether to continue eating or not, whether to act on hunger or satiation, and perhaps how much energy to drive the body to expend. But ultimately the deciding factor on whether a person gets fatter or leaner is the balance of energy expended or consumed—calories-in minus calories-out—and this is regulated by the brain. The fat tissue’s say in the matter is mostly relegated to its secretion of leptin and other adipokines, as these fat-derived hormones are known, that might in turn work in the brain to curb hunger or maybe work in the body to increase expenditure. Energy balance, though, drives adiposity and energy balance (energy homeostasis, as its often called) is ultimately a brain thing not a body thing.

The twist that the food reward/palatability hypothesis of obesity gives to this energy balance paradigm is to make the meaningful effect of a fattening food that of changing the neurochemical balance in the brain. This in turn changes set point and adiposity increases (or decreases) in response. This scenario can appear to be one that rejects, as I do, the simplistic calories-in-calories-out idea, but I’m going to argue that this appearance is an illusion. And that, as I said, is one reason why the hypothesis irks me so.

Here’s one way to look at these two competing paradigms, now with the food reward/palatability hypothesis of obesity standing in for the conventional wisdom:

Here’s the fat-rules paradigm: We’re not getting fat because we are overeating; we are overeating because we’re getting fat—because a hormonal disorder, caused by the consumption of certain foods (refined grains, easily-digestible starches and sugars) drives us to accumulate fat in our fat tissue.

And here’s the food reward/palatability hypothesis, a brain-rules hypothesis: We’re not getting fat because we are overeating; we are overeating because our brains are driving us to get fat—because a neurochemical disorder, caused by the consumption of certain foods (refined grains and sugars, as well as fats and salty foods and industrially processed foods of other types as well), in turn drives us to accumulate fat in our fat tissue.

So you can see how confusing this can be, how similar these two hypotheses can appear. But the question ultimately is how does the brain go about increasing fat accumulation in the food reward/palatability hypothesis. What do these neurochemical changes do to the brain and then what does the brain do that ultimately leads to more fat in the fat cells, which are, after all, mostly half-a-body or so away? What’s ultimately driving the fat?

Here’s where the food reward/palatability hypothesis seems to collapse back down to just another failed twist on calories-in-calories-out. It’s yet another attempt to explain why fat people get fat, and why it’s caused by eating too much (or exercising too little), without explicitly blaming obese or overweight individuals for not being able to control their behaviors (as we lean people do). Chapter 7 in Why We Get Fat goes into this problem in detail.

(A caveat here: I’m willing to be convinced that this hypothesis is not an energy balance hypothesis, and so not a brain-rules-and-the-fat-passively-follows notion, but so far I haven’t seen an argument that’s convincing. I confess, though, that I find the hypothesis surprisingly difficult to understand, which suggests that either I’m losing my intellectual facilities in my dotage — always possible — or that I’m so blinded by my love of my own hypothesis that I refuse to understand it—at least equally likely — or maybe, just maybe, that Dr. Guyenet and other proponents of the hypothesis don’t really understand it either.)

The food reward/palatability hypothesis: looking for a mechanism

As Dr. Guyenet says, as I quoted above, the chain of causality in this hypothesis goes like this: “abnormalities in parts of the brain that regulate body fatness, metabolism and reward/motivation… can lead to weight gain and metabolic problems…” But he doesn’t say how. How do abnormalities in parts of the brain lead to weight gain? The answer seems to be that the brain raises our adiposity set point, but then how does that actually make us fatter? Now we have a change in the brain — set point has gone up — but we still have to explain the change in the body — adiposity increases. How does that happen?

And the answer is that the brain affects this change in fat mass, as proponents of the hypothesis seem to see it (or seem to see it most often), by either increasing food consumption or decreasing expenditure. So the brain is regulating the fat mass not by regulating fat accumulation directly, but by making us eat more and maybe expend less — calories-in-calories-out. And fat people get fat not because their fat tissue is living for itself, as Bauer put it, and increasing its stock of fat, independent of the nutritional state of the organism, but because fat people either respond to rewarding foods differently than lean people do or because they can’t resist this drive to eat more food once their set point goes up. Lean people either can resist the urge, or the rewarding foods don’t have the same neurochemical effects in their brains. Either way, the brains of lean people are more resistant to fattening foods (those with high food reward/palatability value) than the brains of fat people, and the body, in either case, is kind of irrelevant.

Now, the brain could regulate fat mass directly by increasing, for instance, insulin secretion via increased stimulation of the vagus nerve, but Dr. Guyenet would like to dismiss the role of insulin in excess fat accumulation. (This is another post I’ve promised in my last post and one that might come along, well, maybe in a month or two, after we’re done with these food reward posts). As a result, this particular mechanism is not apparently part of the hypothesis.

When I asked Dr. Guyenet, shortly after my last post, why he believed so strongly that the food reward hypothesis was not an energy balance idea, he suggested that I could significantly improve my understanding of this issue by reading his current mentor Michael Schwartz’s 2006 review article in Nature – “Central nervous system control of food intake and body weight.”

A lengthy but not necessarily irrelevant digression

Curiously enough, I had a run-in with Professor Schwartz himself over precisely this issue back in March 2005 when I was reporting Good Calories, Bad Calories. Schwartz built his reputation in obesity research in part by demonstrating that insulin in the brain suppresses food intake – or at least that it does when it is injected directly into the cerebral spinal fluid of baboons. He then argued that this is the hormone’s primary role; Dr. Guyenet is now making very similar arguments. In their opinion, what happens in the brain trumps what happens in the body. Schwartz has actually suggested that one reason for the obesity epidemic may be that we’re not secreting enough insulin because we’re not eating enough carbohydrates. Dr. Guyenet does not go that far.

I argued in an e-mail exchange with Schwartz that because insulin is secreted in the periphery, and that because it can be shown in both humans and animals that increasing insulin in the periphery increases fat accumulation, this would seem to be the primary effect. The appetite-suppression effect in the brain, therefore, would be a secondary effect—a negative feedback loop of the kind that you would expect to see in a homeostatic system.

Schwartz took exception to being questioned by a journalist and he argued that the role of journalists in this field was that of ”helping to debunk profit-motivated, unscientific views that are so prevalent in our culture.” I took exception to being told what my journalistic role should be and replied that my role was to help debunk unscientific views prevalent in our culture, regardless of their institutional provenance or apparent motivation. It took us several e-mails back and forth to achieve a peaceful co-existence again.

Back on track: the mechanism of food reward/palatability

The Schwartz article that Dr. Guyenet suggest I study, though, makes it relatively clear that the food reward/palatability hypothesis of obesity is indeed firmly entrenched in the energy balance paradigm. (I pointed this out to Dr. Guyenet in an e-mail, and he said he would get back to me on it. Apparently other concerns interceded on his side, though, and so I write this without benefit of his clarification.) “Through a process known as energy homeostasis,” Schwarz and his co-author write, “food intake is adjusted over time so as to promote stability in the amount of body fuel stored as fat.” And energy homeostasis, they explain, is regulated via a negative feedback model:

Introduced more than 50 years ago, the `adiposity negative-feedback’ model of energy homeostasis is founded on the premise that circulating signals inform the brain of changes in body fat mass and that in response to this input, the brain mounts adaptive adjustments of energy balance to stabilize fat stores.

So the brain adjusts energy balance (intake and expenditure) to stabilize fat stores; the brain rules, we eat more or expend less, and the fat tissue inflates or deflates accordingly. And this is why Dr. Guyenet and others can write thousands of words about food reward and palatability without ever actually discussing the hormonal/enzymatic regulation of the fat tissue itself, which is, after all, the ultimate organ of interest, and without discussing the hormonal/metabolic regulation of fatty acid oxidation in the lean tissue, when it’s the fatty acids that are ultimately being stored.

The alternative would be to suggest that the brain adjusts fat stores directly via hormonal and central nervous system mechanisms, and this leads to compensatory changes in energy balance. But then, as I said, we would have to discuss the direct peripheral effect of insulin on fat storage and fatty acid oxidation, and that’s not allowed.

“Obesity, by definition, results from ingesting calories in excess of ongoing requirements,” Schwartz and his co-author write, and I’m arguing that any researcher who makes this statement for any reason other than to make the point that it’s meaningless and misleading is living and working in an energy balance paradigm — calories-in, calories-out.

And because I think the energy balance paradigm of obesity is more or less the root of all scientific evil in this business — not just because it’s taken obesity researchers down a century-long blind alley, but because of its implications that fat people just can’t control their urges the way lean people do — I find Dr. Guyenet’s promotion of this hypothesis and its acceptance, limited as it may be, in the paleo and low-carb blogospheres to be very disheartening. I could be wrong (of course) about the scientific bankruptcy of this hypothesis, but I’m going to argue (of course) that I’m not.

In my next post—just a few days from now, I promise (barring extenuating circumstances like the Hayward fault underlying our neighborhood deciding to go off with a magnitude significantly higher than the 3 to 4s we’ve been getting for the past two weeks) — we’ll continue this discussion by looking at the other major limitations of this hypothesis, beginning with some recent observations that it can’t seem to explain.

Filed Under: Calories-in-Calories-out, food reward/palatability hypothesis, General, Obesity and weight regulation

Catching up on lost time – the Ancestral Health Symposium, food reward, palatability, insulin signaling and carbohydrates… Part II(e, as in “end” and “enough already”)

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

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

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

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

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Good Calories, Bad Calories (2007)

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