TAMPA, FLA. (FRONTLINE MEDICAL NEWS) – The far higher rate of eating disorders in women than men appears to be explained at least in part by a greater acute depletion of tryptophan, which is essential for the formation of serotonin, a key mediator of risk, according to a research review presented at the annual meeting of the American College of Psychiatrists.

“The specific vulnerability of women to eating disorders relates to the fact that women’s brains are much more sensitive to dietary intake of tryptophan than are men’s brains,” explained Allan S. Kaplan, MD, senior scientist at the Center for Addiction and Mental Health at the University of Toronto.

Almost 20 years ago, moderate dieting was found more likely in women than men to lower plasma tryptophan levels, impairing serotonin synthesis, according to Dr. Kaplan. About this time, a separate study associated acute tryptophan depletion with relapse of bulimia and depression in women. There is now a coherent hypothesis to explain why.

“Women are more likely than men to be dieting,” said Dr. Kaplan, walking through the evidence. “Low-calorie diets tend to be high in protein and low in cholesterol and fat. Such diets lead to tryptophan depletion and decreased serotonin synthesis in the brain. Because of lower levels of central serotonin, women are more vulnerable to mood and eating disorders than men.”

Not all women who diet may be vulnerable to this sequence of events. Genetics are likely to be a factor, according to Dr. Kaplan, who said, “Genes load the gun; the environment pulls the trigger.”

However, women do appear to be more susceptible for a number of reasons. For one, the mean rate of serotonin synthesis is 52% higher in normal males than normal females, giving them a greater buffer when dietary intake of tryptophan is low. For another, there is evidence that intake of nutrients most rich in tryptophan, particularly proteins, is typically lower in women than men.

The ratio of females to males for both anorexia nervosa and bulimia nervosa is about 10:1. Although the female-to-male ratio of binge eating is lower at 2:1, women dominate these psychiatric diagnoses. Several environmental factors associated with eating disorders are more closely associated with women than men, including a history of sexual or physical abuse and female preoccupation with body image, but acute tryptophan depletion may be an important factor participating in the translation of risk to an active disease, according to Dr. Kaplan.

Acute tryptophan deficiency may also explain why treatment of eating disorders with SSRIs has been disappointing. With low levels of tryptophan leading to serotonin depletion, “there is no substrate” for drugs administered to increase serotonin-mediated signaling, Dr. Kaplan explained.

Ensuring adequate dietary intake of tryptophan, which is “found mainly in high-protein animal foods,” may be important, even though Dr. Kaplan warned that achieving optimal levels of serotonin “can be challenging from food alone.” Nevertheless, behavioral therapies are commonly effective for eating disorders, presumably at least partially as a result of their ability to normalize diet.

Overall, the tryptophan hypothesis has provided a major shift in the understanding of eating disorders, according to Dr. Kaplan. Further studies are needed, but he said that the key message is that, “For women’s brains, you are what you eat.”

Dr. Kaplan reported no conflicts of interest relevant to this topic.

This story was updated on 2/25/2018.


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