Good Calories, Bad Calories

This alternative hypothesis may also tell us something profound about the relationship between nutrition and fertility. That shouldn’t be surprising, because reproductive biologists, as we discussed earlier (see Chapter 21), have long considered the availability of food to be the most important environmental factor in fertility and reproduction. By this hypothesis, the critical variable in fertility is not body fat, as is commonly believed, but the immediate availability of metabolic fuels. This was suggested in the late 1980s, when the reproductive biologists George Wade and Jill Schneider described their research on hamsters, which were chosen because of their clockwork four-day estrous cycles. The experiments were remarkably consistent. These animals will go into heat whether they are fat or lean, and they will continue to cycle, as long as they can eat as much food as they want. If both fatty-acid and glucose oxidation are inhibited, however, and they’re not allowed to increase their food intake in response, their estrous cycles stop. They’ll remain infertile, whether they are gaining or losing weight at the time. These animals are responding to the general availability of metabolic fuels. The same observation has been made about pigs, sheep, and cattle. Monkeys will shut down their secretion of the hormone that triggers ovulation if they go twenty-four hours without food, but they’ll re-establish secretion immediately upon eating. The more the monkeys are allowed to eat, the more hormone they’ll secrete.

If it is true that fertility is determined by the availability of metabolic fuels, as Wade and Schneider explained, then “it would be expected that ovulatory cycles would be inhibited by treatments that direct circulating metabolic fuels away from oxidation and into storage in adipose tissue.” This is what insulin does, of course, and, indeed, infusing insulin into animals will shut down their reproductive cycles. In hamsters, insulin infusion “totally blocks” estrous cycles, unless the animals are allowed to increase their normal food intake substantially to compensate. This hypothesis can also explain the infertility associated with obesity in both humans and lab animals. If “an excessive portion of available calories” is locked away in fat tissue, then the animal will act as if it’s starving. In such a situation, Wade and Schneider said, “there will be insufficient calories to support both the reproductive and the other physiological processes essential for survival” reproductive activity shuts down until more food is available to compensate.

This metabolic-fuel hypothesis of fertility has escaped the attention of clinicians. The clear implication is that a woman struggling with infertility or amenorrhea (the suppression of menstruation) will benefit more from a diet that lowers insulin but still provides considerable calories—a low-carbohydrate, high-fat diet—and thus repartitions the fuel consumed so that more is available for oxidation and less is placed in storage.

If this hypothesis of hunger, satiety, and weight regulation is correct, it means that obesity is caused by a hormonal environment—increased insulin secretion or increased sensitivity to insulin—that tilts the balance of fat storage and fat burning. This hypothesis also implies that the only way to lose body fat successfully is to reverse the process; to create a hormonal environment in which fatty acids are mobilized and oxidized in excess of the amount stored. A further implication is that any therapy that succeeds at inducing long-term fat loss—not including toxic substances and disease—has to work through these local regulatory factors on the adipose tissue.

If the principal effect of a drug, for example, is to suppress in the brain the desire to eat, and thus reduce food consumption, then the body will perceive the consequences as caloric deprivation and compensate accordingly. Energy expenditure will be reduced, and weight loss will be temporary at best. On the other hand, any drug that works locally on the fat cells to release fatty acids into the circulation will inhibit hunger because it will be increasing the flow of fuel to the cells. This could also be the case for any treatment that appears to increase metabolism or energy expenditure. A weight-loss drug that works in the brain to increase metabolism will also increase hunger, unless it also works on the fat tissue to mobilize fatty acids that can supply the necessary fuel.

Consider nicotine, for instance, which may be the most successful weight-loss drug in history, despite its otherwise narcotic properties. Cigarette smokers will weigh, on average, six to ten pounds less than nonsmokers. When they quit, they will invariably gain that much, if not more; approximately one in ten gain over thirty pounds. There seems to be nothing smokers can do to avoid this weight gain.