shrinking because he was eating less. “The result would appear to be a ‘negative energy balance,’” Pennington said, “because so much of the energy needs would be supplied from stored amounts.”
Energy expenditure would also increase on such a diet. The now unconstrained flow of fat calories from the adipose tissue would increase the fuel available for cellular metabolism. The cells would no longer be undersupplied, as though living in a constant state of semi-starvation, and their metabolism would no longer be inhibited. Metabolic rate would increase, as would the impulse to physical activity—the urge to expend some of the energy now freely available. That such an effect is possible in humans, Pennington said, had been one of the observations reported by Du Bois and his colleagues in their yearlong all-meat-diet experiment with Stefansson and his colleague Anderson. These investigators had measured Stefansson’s and Anderson’s metabolism on a balanced diet and then measured their metabolism repeatedly during the yearlong trial. Both men lost some weight while eating the meat diet; both increased their basal-metabolic rate—7 percent for Stefansson and 5 percent for Anderson. Such an increase in energy expenditure could account for a weight loss of twenty pounds or more over the course of a year. If this change in expenditure went in the other direction when the diet included carbohydrates, it could easily account for the slow development of obesity.
When the obese or overweight go on a carbohydrate-restricted diet, Pennington theorized, there will be an increase in metabolic and physical activity as their bodies expend this newly available energy, and an attendant weight loss. The naive assumption would be that the physical activity caused the weight loss, and it would be wrong. They will finally be burning off their accumulated fat stores and putting that energy to use.
Under these conditions, the energy expenditure of the obese individual might rise to what it otherwise would have been in a healthy state. It was not out of the question, as Frank Evans had reported and Sidney Werner had speculated, that this might be more than four thousand calories a day for someone who was definitively obese. Such an individual might easily eat over three thousand calories a day and still lose a pound or two a week.
This brings us back to the questions we asked earlier: If people eat less on carbohydrate-restricted diets, why aren’t they hungry. And if they don’t eat less, why do they lose weight? If the restriction of carbohydrates works to ameliorate this defect in fat metabolism, as Pennington speculated, then weight will be lost, hunger will be absent, and calorie consumption may decrease, while energy expenditure will increase. This is no more than the consequences of the law of energy conservation applied to a biological system that works to conserve body composition and maintain a healthy flow of fuel to the cells and tissues.
In an ideal world, Pennington’s metabolic-defect hypothesis of obesity would have been tested directly. Instead, it was ignored. Pennington made this easier by speculating that the root cause of obesity was an inability to metabolize properly a compound called pyruvic acid. This made physiological sense, but further research quickly refuted it. Pennington’s error allowed his contemporaries in nutrition and obesity research to dismiss him as just another renegade who refused to accept the reality of energy conservation. He deserved far better, as it wouldn’t be long before researchers pinned down the precise nature of the metabolic-hormonal defect that appears to be the driving force in the accumulation of excess fat.
THE CARBOHYDRATE HYPOTHESIS, I: FAT METABOLISM
Looking at obesity without preconceived ideas, one would assume that the main trend of research should be directed toward an examination of abnormalities of the fat metabolism, since by definition excessive accumulation of fat is the underlying abnormality. It so happens that this is the area in which the least work has been done.
HILDE BRUCH,
IN JUNE 1962, EDWIN ASTWOOD OF Tufts University gave the presidential address to the annual meeting of the Endocrinology Society in Chicago. Although Astwood was not known as an obesity researcher, he nonetheless took the opportunity to present what he considered the obvious explanation for its cause. A physician who had spent thirty years studying and treating hormone-related disorders, Astwood had discovered the reproductive hormone luteotropin (now known as luteinizing hormone), and he had created the standard technique for purifying pituitary hormones. He had performed what
Astwood believed that obesity and a disposition to fatten are genetic disorders. If genes determine stature and hair color, the size of our feet, and a “growing list of metabolic derangements,” he asked, then “why can’t heredity be credited with determining one’s shape?” Although it’s possible to fatten animals by stuffing them, “and doubtless we could do the same thing to ourselves if we put our minds to it,” Astwood did not consider this a cause of overweight. “Not many people try to get into the circus this way,” he said—“they become candidates spontaneously.” He also considered inactivity to be of dubious importance. “Many of our moderately fat patients sit like bumps on a log,” he said, but that could be an effect, not a cause. “It would be interesting to know whether adiposity and inertia go together for some reason common to both. If fatty acid is needed for energy, a deficit could indeed promote lethargy and indolence.”
Astwood then described what had been learned over the past thirty years about the hormonal regulation of fat metabolism. “To turn what is eaten into fat, to move it and to burn it requires dozens of enzymes and the processes are strongly influenced by a variety of hormones,” he explained. Sex hormones, for instance, determine where fat is stored, as evidenced by the differences in fat distribution between men and women. Thyroid hormones, adrenaline, and growth hormone accelerate the release of fatty acids from fat depots, as does a hormone known as glucagon, secreted by the pancreas. “The reverse process,” Astwood said, “the reincorporation of fat into the depots and the conversion of other food to fat, tends to be reduced by these hormones, but to be strongly promoted by insulin.” All of this demonstrated “what a complex role the endocrine system plays in the regulation of fat.”
Finally, Astwood speculated on what he considered the simplest possible explanation for obesity, and here he echoed Alfred Pennington, although, if he had read Pennington’s work, he neglected to mention it. “Now just suppose that any one of these (or other unlisted) regulatory processes were to go awry,” Astwood said.
Suppose that the release of fat or its combustion was somewhat impeded, or that the deposition or synthesis of fat was promoted; what would happen? Lack of food is the cause of hunger and, to most of the body, [fat] is the food; it is easy to imagine that a minor derangement could be responsible for a voracious appetite. It seems likely to me that hunger in the obese might be so ravaging and ravenous that skinny physicians do not understand it.
There is no reason to suppose that only one of these mechanisms ever goes wrong…. There are so many possibilities here that I am willing to give odds that obesity is caused by a metabolic defect. I would not want to wager about how many enzymes determine the shape of voluminous pulchritude.
This theory would explain why dieting is so seldom effective and why most fat people are miserable when they fast. It would also take care of our friends, the psychiatrists, who find all kinds of preoccupation with food, which
