Desperately Seeking a Flab-Fighting Formula

By Christine Gorman

If only there were a magic potion for losing weight. The morning trudge to the bathroom scale would no longer be so disheartening. The obligatory resolution to shed a few pounds would be easier to keep. And the canny scientists and entrepreneurs who developed this antiflab formula would be richer than Ross Perot. Unfortunately, repeated efforts to produce a weight-loss wonder drug have been no more successful than Perot's presidential bid. Dozens of diet pills have come and gone, raking in billions of dollars for pharmaceutical manufacturers. But for long-term effectiveness, the pills might as well have been chocolate-covered bonbons.

In labs and clinics around the world the search goes on, and -- hold your breath -- there seems to be progress. In the past several years scientists have discovered a great deal about how the body creates and sustains its craving for food. They now believe that, at least in some cases, they have learned enough to block such biological triggers with drugs. No one is claiming a cure for obesity, but the early results are encourageing. "For the first time, I feel that I have some ability to actually help people lose weight beyond simply trying to motivate them," says Dr. Michael Hamilton of Duke University.

The new treatments, which are still in the experimental stage, include several drugs not yet approved by the Food and Drug Administration and some that are available by prescription but up to now have been used for purposes other than weight loss. They appear to be much safer than addicive amphetamines -- whose widespread abuse 20 years ago temporarily gave diet pills a bad reputation -- and may be far more effective than the many popular over-the-counter remedies, such as Dexatrim and Acutrim, that are marketed as appetite suppressants. Nonetheless, Hamilton and other doctors caution that the new medications do not work for everyone and cannot do the job entirely on their own. Those old stalwarts, diet and exercise, still play a crucial role in any good weight-loss program. All that drugs can do is tilt the odds in favor of success. "It's a way of modifying the struggle," says Dr. Arthur Frank, director of the obesity clinic at George Washington University. "It can offer a 10% to 20% boost."

To be effective, a weight-loss drug must counteract some of the body's most basic biological mechanisms. Evidence suggests that weight is controlled in much the same way that a thermostat regulates room temperature. According to this explanation, known as the set-point theory, the brain plays an importatnt role in determining a person's ideal weight, which remains more or less constant throughout adult life. Whenever a person loses weight, a portion of the brain called the hypothalamus responds by increasing the appetite and slowing the metabolism so that the body can store more fat. By contrast, when a person gains weight, the hypothalamus decreasses appetite and speeds metabolism. However, the brain does not seem to work as hard to ward off weight gain as it does to combat weight loss; overeating can overload the system. Moreover, the discovery of an obesity gene suggests that many people inherit a tendency to maintain a set point that is too high.

Like more tradtiional approaches, the latest obestity treatments try to lower an elevated set point by decreasing a person's appetite. But they have added a new twist by also affecting the level of a chemical in the brain called serotonin. A shortage of this chemical has been linked to depression and other mental ills. Serotonin may curb the appetite by helping a person feel full and satisfied. And, it turns out, a growing body of research suggests that fatty foods can increase the amount of serotonin in the brain. So it appears that some people who are obese do not make enough serotonin and are in effect trying to treat their depression, or at least feel more satisfied, by overeating. That is why antidepressant drugs, like Prozac, seem to help people shed pounds. Unfortunately, the results are short-lived: patients lose weight at first, but after a year's treatment they have usually gained all of it back.

So far, the most successful medical regiments have addressed both mood and appetiete control. In a four-year study, Dr. Michael Weintraub, formerly of the University of Rochester and now at the FDA, found that a combination of the drug phentermine, which seems to speed metaboliusm, and fenfluramine, which may boost serotonin levels, improved an obese person's chances of losing weight. Of the 120 people in the study, those who took the drugs achieved an average 16% weight loss over eight months, compared with a 5% loss for those who had to depend on diet and exercise alone. By the end of the trail, nearly all participatnts had added back some of the lost weight, but those who were part of the drug-treatment group had regianed fewer poiunds. More research is needed to identify possible side effects.

Many doctors are beginning to view obesity as a chronic disease, much like high blood pressure or diabetes, that requreies lifelong therapy. The ailment can be controlled but not conquered, and treatment cannot stop even when the bathroom scale reports good results.

With reporting by Ann Blackman/ Washington and Alice Park/New York