“What happens when low calorie diets are applied is that the starved tissues of the obese are starved further,” Pennington wrote. Since the consequences of this food deprivation are likely to be the same in the obese as in the lean, they had already been adequately described by the semi-starvation experiments of Benedict and Keys. “The first noticeable effect of such a calorie shortage is limitation of the voluntary activities of leisure hours,” Pennington wrote. “The various avenues of caloric expenditure are all contracted in adjustment to the diminished food intake…and thus deflect the purpose for which low calorie diets are prescribed.”

“A more rational form of treatment,” Pennington suggested, would be one that makes fat once again flow readily out of the fat cells, that directs “measures primarily toward an increased mobilization and utilization of fuel” by the muscles and organs. Pennington believed that this is what carbohydrate restriction accomplished and this was why the diets worked. The cells would respond to this increased supply of fuel by accelerating the rate of metabolism—utilizing the fuel. Now the body would have to establish a new equilibrium between the three variables of the energy-balance equation—energy storage, intake, and expenditure. This new equilibrium, however, would be commensurate with a healthy—i.e., uninhibited—flow of fat from the adipose tissue.

If Pennington was right, a high-protein, high-fat diet that was restricted in carbohydrates but not calories would correct the metabolic fault. The adipose tissue (i.e., energy storage) would shrink, because fat would no longer be trapped in the fat tissue. It would flow out at an accelerated rate, and this would continue until a healthy equilibrium was reestablished between fat storage and fat release. Appetite (i.e., energy in) would adjust downward to compensate for the increased availability of fuel from the fat tissue. Edward Adolph of the University of Rochester and Curt Richter of Johns Hopkins had repeatedly demonstrated that laboratory animals will increase or decrease their food intake in response to the available calories. Slip nutrients into their drinking water or deposit them through a tube directly into their stomachs, and the animals compensate by eating less. Dilute their food with water or indigestible fiber, and the animals compensate by consuming a greater volume to get the same amount of calories. There is no reason to think that this adjustment in caloric intake will not occur if the increase in available nutrients comes from the internal fat stores, rather than external manipulations—no reason to think that the body or its cells and tissues could tell the difference. “Mobilization of increased quantity of utilizable fat, then, would be the limiting factor on the appetite, effecting the disproportion between caloric intake and expenditure which is necessary for weight reduction,” Pennington wrote.