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.