Good Calories, Bad Calories (77 page)

The funding of research projects, laboratories, and entire academic centers by the food and pharmaceutical industries is now a fact of life in modern medical research, which is why many journals require that their authors declare potential conflicts of interest. But it raises important questions, just the same. When Science dedicated special issues to obesity research in 1998 and again in 2003, James Hil from the University of Colorado was selected both times to write the review article on diet and lifestyle factors that influence weight gain. In those articles Hil argued that passive overeating and sedentary behavior were the causes of obesity, and he recommended reducing fat in the diet. Hil had long been a defender of the role of carbohydrates and particularly sugar in weight regulation. He even wrote an article, paid for by the Sugar Association, promoting the use of sugar in weight-loss diets, under the assumption that a high-carbohydrate diet, even if loaded with sugar, would “reduce the likelihood of overeating, rather than increasing it, as some popular diet theories purport.” (“The theory that dietary sugar equals high insulin levels equals excess fat deposits is unproven and makes little biological sense,” Hil wrote.) Over the years, as Hil has acknowledged in his conflict-of-interest statements, he has also received consulting fees from Coca-Cola, Kraft Foods, and Mars (makers of Snickers, M&M’s and Mars Bars), companies that would stand to suffer significant setbacks if the notion of the fattening carbohydrate was institutionalized as a fact of science. He has also received over $2 mil ion in what are technical y termed “gifts” to his laboratory from Procter & Gamble, the maker of the fat substitute olestra, which has been described in the press as potential y a “dieter’s dream.”

Olestra’s only reason for existence is that it wil al egedly help us manage our weight by replacing fat in the diet and making it easier for us to consume a low-fat, low-calorie diet. If carbohydrates are the fattening nutrients in human diets rather than fat or al calories, as Atkins suggested, then these diets have no role in weight loss or weight regulation, and olestra’s rationale vanishes.

If the study of weight regulation were a legal issue, rather than a medical and scientific one, the support from Procter & Gamble would have been considered reason enough for Hil to recuse himself from any discussions of the dietary treatment of obesity or participation in any dietary trials that might directly influence Procter & Gamble’s profitability, and thus perhaps Hil ’s interests.

In 2002 and 2003, Hil also received over $300,000 a year from the NIH to do a clinical trial testing the Atkins diet against a low-calorie, low-fat diet and, by implication, the justification for olestra as a fat substitute in a weight-reduction diet. And Hil was one of three principal investigators in the fol ow-up trial of the Atkins diet, for which the NIH provided $5 mil ion. The salient question is whether Hil and the other academics in this pursuit are any less open to having their interpretation of the evidence influenced by financial considerations than Atkins or Tal er or any of the other diet-book authors.

“A resolution of the very controversial question of the efficacy of low carbohydrate diets has great practical and theoretical significance,” wrote Donald Novin of UCLA in 1978. Because a generation of obesity authorities were determined to dismiss the practical significance of carbohydrate-restricted diets, they dismissed the potential theoretical significance at the same time. Obesity researchers today say they stil have no hypothesis of weight regulation that can explain obesity and leanness, let alone account for a century of paradoxical observations. They insist that obesity is inevitably caused by overeating and thus consuming more calories than we expend, but when asked what causes someone to overeat, they have no answer. Yet the research on insulin and fat metabolism offers one, and it has for several decades.

THE CARBOHYDRATE HYPOTHESIS, III: HUNGER AND SATIETY

There is only one way to lose weight, and that is to grow accustomed to feeling hungry. This simple fact, known to most people in affluent countries, seems somehow lost on the authors of the diet, weight-loss, and exercise books that find their lucrative way through the drugstore book racks. Two questions, then: Why do they fail to mention it? And why is it so?

Emory University anthropologist Melvin Konner,

The Tangled Wing, 2003

IN 1975, THE DUKE UNIVERSITY PEDIATRICIAN James Sidbury, Jr., described a “rational basis” for the dietary treatment of childhood obesity, one that would neither torment his young patients with hunger nor rely on pharmaceutical means to prevent it. Such a diet, he wrote, would induce weight loss with a

“minimum of anguish and struggle.” Sidbury had an advantage over other investigators treating obese patients in that he had spent his career studying disorders of carbohydrate metabolism and, indeed, had already earned international renown for his development of a diet, stil used today, to treat what are cal ed glycogen storage diseases. The same year Sidbury published his description of a “Program for Weight Reduction in Children,” however, he left his clinic at Duke to become director of the National Institute of Child Health and Human Development at NIH. By then, he had written only one short textbook chapter discussing his dietary treatment and one three-page article for an obscure journal cal ed Connecticut Medicine. In them, he described an approach to obesity therapy that differed from Robert Atkins’s only in the details of the application: Sidbury’s diet was very low in both carbohydrates and calories, and Sidbury was writing for medical professionals, not the general public.

He based the design of his diet on several key observations. Fasted children “rarely, if ever, complained of hunger,” Sidbury noted, and the “enzymes of lipogenesis”—insulin—rapidly decrease during fasting. Insulin is chronical y elevated in obese patients, and the obese children referred to him in his practice typical y consumed a diet dominated by carbohydrates—“crackers, potato chips, French fries, cookies, soft drinks, and the like.” These foods are digested and absorbed as simple sugars, Sidbury explained, “chiefly glucose, which is the most potent stimulator of insulin release and synthesis.”

Since insulin wil “facilitate lipogenesis” and inhibit the release of fat in the adipose tissue, this in turn created what Sidbury cal ed the “milieu for positive fat balance” in the cel s of the adipose tissue. “Thus it was reasoned,” Sidbury wrote, “that a low carbohydrate diet would create the conditions vis-à-vis insulin metabolism which would decrease the constant stimulation of the [insulin-secreting] cel s of the pancreas. The decreased insulin levels would then permit normal fatty acid mobilization.”

The diet that Sidbury eventual y used in his clinic and claimed to be uniquely effective contained only 15 percent carbohydrates—“the remaining being apportioned approximately equal y between protein and fat”—and from three to seven hundred total calories a day, depending on the child’s age. The older the child, the more calories al owed. “Many parents do not believe their child can be satisfied with so little food,” Sidbury wrote. “Their attitude changes completely,” however, when they see the “obvious change in the amount of food which satisfies the children.”*131

The phenomena of hunger and satiety have been the running subtext of al our discussions of obesity: the “persistent clamor of hunger” that attends semi-starvation diets; the absence of hunger during fasting and carbohydrate restriction; the question of whether insulin works as a fattening hormone or a hunger hormone when used to treat anorexia. And then, of course, there is the association of hunger, or at least positive caloric balance, with weight gain.

If there’s one thing the law of energy conservation does indeed tel us, it’s that anything that works to increase or decrease our body mass must have compensatory effects on the balance of calories consumed and calories expended. Thus, any viable hypothesis of obesity must also be a hypothesis of hunger and satiety, and perhaps, as Alfred Pennington noted, of energy expenditure as wel .

The study of human obesity, however, has included only a few vague conceptions of the physiological underpinnings of hunger and satiety. One common assumption is that when the stomach is empty it contracts, and that signals hunger. By this logic, dietary fat contributes to satiety by prolonging the drainage of nutrients out of the stomach. Another assumption is that hunger is a sensation that exists in the brain, having little or nothing to do with the immediate metabolic needs of the body itself. Though many obesity researchers wil reflexively disagree with this statement, it is essential to the conventional wisdom—that the ability to remain indefinitely on a calorie-restricted diet is a matter of wil power, and the failure to remain on such a diet is a failure of character. Once the pursuit of a therapy for obesity left physiology and biochemistry behind and became a subdiscipline of psychology and psychiatry, and once it was “established” that the only way to lose weight, as Melvin Konner suggested, is to grow accustomed to feeling hungry, the natural focus of virtual y al obesity research became, and has remained, the brain.

By the early 1970s, a handful of hypotheses had been proposed to explain how the brain might induce hunger and satiety, and in turn regulate weight by limiting caloric consumption to match expenditure. Two received the most attention and have entered the textbooks as the most likely explanations. Both hypotheses date to the 1950s; neither took into account the evolving research on insulin, insulin resistance, and fat metabolism. Both had conspicuous deficiencies that would be overlooked.

One is Jean Mayer’s glucostat hypothesis or, technical y, the glucostatic regulation of food intake, and it is invoked to explain the short-term initiation of meals. Receptors in the hypothalamus, said Mayer, metabolize glucose, initiating the sensation of hunger when the available supply of glucose fal s, and provoking satiety when it rises. This glucostatic regulation, as Mayer put it, is an “essential component of the mechanism by which the needs of the body make themselves felt in the satiety centers.” It couldn’t be the only one, however, because it offered no explanation for what Mayer cal ed “the problem of the nature of the very fine adjustment knob…the mechanism which wil make you regain the weight you lost after an il ness, and which makes so difficult the maintenance of weight loss after an arduous weight reduction course.”

The second hypothesis, what the Cambridge University physiologist Gordon Kennedy cal ed lipostatic regulation or the lipostat, would evolve in the 1970s into the remarkably durable notion that we are al endowed with a certain set point of body weight or adiposity that we defend against both caloric deprivation and (perhaps less vigorously) caloric surplus. By Kennedy’s logic, the lipostat is also located in the hypothalamus and accomplishes its fine-tuning job by monitoring the amount of fat in the body or some by-product of metabolism that is released into the bloodstream in relationship to our adiposity. When this adiposity signal dips below an acceptable level—the set point—the lipostat responds by increasing food intake or decreasing energy expenditure. When the adiposity signal moves above this set point, the lipostat works to suppress food intake and perhaps increase expenditure.

According to this hypothesis, the fundamental difference between the lean and the obese is the amount of fat stores that the hypothalamus is set to defend—the set point—not the manner or vigor with which it is defended. Whatever our weight, if we find ourselves in a situation where our current level of body fat is beneath that of our set point, we wil fatten easily until we’ve reached our predetermined level.

This hypothesis is a reformulation based on animal research of what had been considered a fact of life in pre–World War I nutrition textbooks, that

“weight loss triggers the dual pressures of increased food intake and decreased caloric expenditure,” as Stunkard put it. Nonetheless, obesity authorities have typical y considered it unacceptably nihilistic. “It is not appealing from the therapeutic point of view,” as Stunkard said, “because it sounds kind of

…hopeless. If you’re fat and your set point is elevated, you’re in bad shape.” And, of course, if we’re fat, or very fat, it is difficult to argue that our set point is not elevated. Moreover, the hypothesis simply failed to explain how the brain manages to monitor our fat stores, and then raise or lower food intake and energy expenditure in response. Saying that we’re al endowed with a lipostat that monitors our adiposity and then regulates hunger appropriately is just another way of saying that our weight remains remarkably stable, whether we’re lean or obese, and then assigning the cause to a mysterious mechanism in the brain whose function is to achieve this stability.

The more fundamental criticism is that the concept of a set point or a lipostat has little precedent in physiology, whereas the long-term stability of body weight can be explained by a much simpler mechanism that does. Life is dependent on homeostatic systems that exhibit the same relative constancy as body weight, and none of them require a set point, like the temperature setting on a thermostat, to do so. Moreover, it is always possible to create a system that exhibits set-point-like behavior or a settling point, without actual y having a set-point mechanism involved. The classic example is the water level in a lake, which might, to the naïve, appear to be regulated from day to day or year to year, but is just the end result of a balance between the flow of water into the lake and the flow out. When Claude Bernard discussed the stability of the milieu intérieur, and Walter Cannon the notion of homeostasis, it was this kind of dynamic equilibrium they had in mind, not a central thermostat like regulator in the brain that would do the job rather than the body itself.

This is where physiological psychologists provided a viable alternative hypothesis to explain both hunger and weight regulation. In effect, they rediscovered the science of how fat metabolism is regulated, but did it from an entirely different perspective, and fol owed the implications through to the sensations of hunger and satiety. Their hypothesis explained the relative stability of body weight, which has always been one of the outstanding paradoxes in the study of weight regulation, and even why body weight would be expected to move upward with age, or even move upward on average in a population, as the obesity epidemic suggests has been the case lately. And this hypothesis has profound implications, both clinical and theoretical, yet few investigators in the field of human obesity are even aware that it exists.