Why Diets Flop

Hormone may help explain success of stomach surgery

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HealthDay Reporter

WEDNESDAY, May 22, 2002 (HealthDayNews) -- Crash diets rarely work, but stomach-reduction surgeries seem to keep the weight off.

Now, a surprising new study helps explain why the former fail and the latter succeed.

The key isn't simply that the altered organ holds so much less food. Instead, a hormone called ghrelin that's a relative newcomer to the appetite research scene appears to play an important role in keeping calories out of the mouth to begin with.

The new study, published tomorrow in The New England Journal of Medicine, found ghrelin rises in obese dieters, but falls sharply in people who've had gastric bypass operations. What's more, the hormone surges in anticipation of meals in those who deprive themselves of calories -- which is typical of crash dieters -- but stays more or less constant in patients after surgery.

Dr. David E. Cummings, a researcher at the University of Washington in Seattle and lead author of the study, says drugs that block ghrelin might one day help dieters slim down. By the same token, the hormone itself might be a treatment for anorexia, since studies have found that giving it to rodents spurs them to eat. Indeed, ghrelin is the first hormone identified that promotes -- as opposed to quashes -- appetite, he says.

Ghrelin is secreted in the gut, where it acts as a sort of chemical room-service call to the brain for more energy. In other words, people who try to shed pounds by depriving themselves of food through crash diets are fighting against a feedback mechanism that becomes more insistent the more weight they lose.

In gastric bypass procedures, surgeons stitch off most of the stomach to restrict food intake. They also reroute the passage of nutrients to the small intestine, leading to a "dumping" phenomenon that makes eating high-calorie meals unpleasant, says Dr. Joseph F. Capella, a Ramsey, N.J., doctor who performs the operation.

Bypass can lead to radical weight loss of potentially hundreds of pounds in some patients, Capella says. Better still, he adds, he recently published a study in the American Journal of Surgery showing that patients who underwent the procedure keep an average of 77 percent of their lost weight off for at least five years. For crash dieters, that figure is effectively zero, he says. "Essentially, nobody has success with dieting."

Ghrelin's role in appetite has only recently been identified. Unlike its more famous cousin leptin, which acts as a long-term modulator of appetite, ghrelin has hints of a role both in day-to-day mealtime hunger as well as long-term body weight.

In the new study, Dr. David Cummings, of the VA Puget Sound Health Care System in Seattle, and his colleagues compared ghrelin levels in 13 obese men and women trying to lose pounds on low-calorie diets and five who'd had gastric bypass surgery.

For both the crash dieters and 10 "normal-weight" subjects, ghrelin spiked before meals and fell off after eating. As the dieters lost weight, their daily ghrelin levels rose an average of 24 percent.

When the pattern is plotted on a graph, Cummings says, "you can see mountains at each meal, and that entire waveform looks almost the same after weight loss. It's just that the whole thing is shifted upwards."

However, surgery patients had a different pattern. Even after losing an average of 36 percent of their body weight -- about twice as much as the dieters -- their ghrelin levels were nearly three-quarters lower than those of the other two groups. What's more, they remained steady throughout the day with no spikes before meals.

The findings suggest that at least part of the success of gastric bypass may be due to the missing ghrelin, though it's "undoubtedly not the whole story," Cummings says.

Cummings' group plans to test that hypothesis in patients who've undergone "stomach stapling," or gastroplasty, which doesn't reduce ghrelin secretion. He'd also like to test ghrelin-blocking compounds in people to see if they can, in fact, suppress hunger.

Although many drug companies are probably working on ghrelin-blocking drugs, Cummings says it has been difficult for researchers in the public sector to obtain them to use in their own labs.

What To Do: For more information about gastric bypass surgery, try the National Institute of Diabetes and Digestive and Kidney Diseases. More than one-quarter of American adults in 1999 were considered obese, defined as having a body mass index -- a ratio of height to weight -- of 30 or higher, according to the Centers for Disease Control and Prevention.

SOURCES: David E. Cummings, M.D., assistant professor, medicine, University of Washington, VA Puget Sound Health Care System, Seattle; Joseph F. Capella, M.D., Ramsey, N.J.; May 23, 2002, The New England Journal of Medicine

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