The Hunger

The Hunger

The Hunger

Health and medicine explained.
Aug. 29 1997 3:30 AM

The Hunger

Body chemistry--not willpower--is the key to losing those 10 pounds.

"Food is not the boss in my life. I am stronger than the temptation of any food."

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--from the Richard Simmons home page

Then again, maybe not. Americans spend $30 billion a year on weight-loss programs, but obesity resists treatment more tenaciously than do viruses--90 percent to 95 percent of people who lose weight eventually regain it.

Why is that? We've learned much in the last few years about the role that hunger plays in obesity. Drug companies have capitalized on that knowledge to create powerful new appetite suppressants. But these "cures" come with serious risks. Researchers linked the popular diet-drug combination "fen-phen" to a rare heart disease a year ago. But doctors continued to prescribe it to millions, arguing that the health risks associated with obesity justified fen-phen's wide use. Now reports of new heart abnormalities in women on fen-phen raise fresh questions about using pills for obesity before all the facts are in.

Scientists didn't always view appetite as a cause of obesity. The dominant thinking for more than two decades was that the obese gained weight because they burned fewer calories. In experiments, overfed or underfed volunteers always returned to their original weight--the "setpoint"--when they ceased their diets. Also, when obese dieters lost weight, their metabolism slowed, conserving calories and driving their weight back to the setpoint. It seemed that obese people's only option was a combination of starvation and exercise, while skinny people got to feast and watch television. In the late '60s, amphetamine, which increases metabolism, became the rage for dieters. But it didn't keep the weight off, and proved to be addictive.

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As it turned out, thin people didn't have higher metabolic rates. On high-calorie diets, they gained weight just as easily as obese people. (In fact, obese people had to eat more to put on a given amount of weight.) The metabolism of obese dieters never slowed enough to explain how quickly their weight bounced back. They were also eating more. Put simply, even at their baseline weight, obese people eat more than thin people.

Swedish studies of pregnant women demonstrate this observation. Women weighed about a pound more one year after delivery than at the start of pregnancy. Some gained more than a pound, and many returned to their old weight. How were the gainers different from the non-gainers? Mainly, they ate more total calories, especially in the form of snacks. Although gainers ate lunch less often, their snacking increased to three or more times per day.

The study also demonstrated another frustrating fact about setpoints--they're easier to increase than decrease. Experts believe that once you've put on extra weight for six months to a year, the setpoint resets, as it does after pregnancy. To permanently lower the setpoint, you must keep weight off for about three years, perhaps longer. Until recently, nothing short of has kept the seriously obese from eating as much as they want to.

The big breakthrough in understanding obesity came in 1994, when experiments on lab mice revealed that the hormone leptin controls the setpoint by controlling satiety. When your weight falls, leptin decreases, hunger increases, and you eat more--until you return to your weight setpoint. This year, researchers in Cambridge, England, found an inbred family whose members all lacked the gene for producing leptin. Without leptin to signal satiety, the children in this family eat ravenously. The 2-year-old weighs 64 pounds and the 8-year-old, 189 pounds.

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These leptin findings imply that hormones and neurotransmitters control the instinctual desire to eat, overwhelming willpower in the process. In evolutionary terms, this makes sense. The drive to find and eat food was integral to the survival of our early ancestors. People who gorged themselves survived winter famines and reproduced more than others. But this behavior became "maladaptive" when access to round-the-clock hamburgers and ice cream became the norm. Now, as we gain weight and push our setpoints upward, we are reprogrammed to eat even more.

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T he leptin breakthrough spurred efforts to manipulate the brain's hunger centers. In 1995, a combination of two drugs, fenfluramine and phentermine--fen-phen--was shown to suppress appetite enough to help the severely obese lose an average of 24 pounds after two years. Fenfluramine increases the brain's serotonin levels (Prozac does, too, but not as dramatically) to produce a sense of satiety. Phentermine is a relative of amphetamine that reduces hunger and increases metabolism. Not surprisingly, when the obese patients stopped taking these drugs, their weights returned to baseline levels. But fen-phen was the first drug therapy proven to reduce weight over the long haul.

Other drugs for the hyperhungry are on the way. Dexfenfluramine (tradenamed Redux), a cousin of fenfluramine, was just released. Sibutramine, with fen-phen's effects in one pill, and orlistat, which prevents fat absorption from the intestines, are undergoing Food and Drug Administration approval testing. Leptin analogues (chemical cousins) are also being developed. Effective hunger control will probably require lifelong therapy with multiple drugs like these.

The first warning that these drugs could pose health risks came a year ago, when the New England Journal of Medicine published an article by French researchers linking fen-phen to a deadly cardiac disease called primary pulmonary hypertension. The study suggested that between 23 and 46 of every 1 million patients taking fen-phen would die from the condition each year. (At my hospital, a young woman died from it after taking fen-phen for 24 days to lose weight for her wedding.) Yet, the New England Journal of Medicine downplayed the risks at the time. It simultaneously published an editorial speculating that fen-phen would save more lives by reducing obesity than the associated heart disease would kill.

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The French findings were basically ignored: Eighteen million prescriptions were filled for fen-phen in the United States last year. Physicians opened offices and Internet sites to do nothing but prescribe fen-phen, and weight-loss operations like Jenny Craig and Nutri/System placed fen-phen prescription-writing doctors at the center of their programs.

Fen-phen consumption began to fall only this month, when the New England Journal of Medicine essentially withdrew its earlier cost-benefit argument with the emergency release of startling new fen-phen findings. Researchers in Minnesota and Nebraska documented 24 cases of unusual heart-valve abnormalities in women taking fen-phen. The average age of the patients was 43, and five required valve-replacement surgery. This week, the FDA reported 58 new cases of abnormal heart valves in patients on fen-phen, and the Journal of the American Medical Association reported animal evidence linking both dexfenfluramine and fenfluramine to toxic brain effects.

There are three reasons why nobody should have bought the obesity-is-deadlier argument. 1) Obesity's risks come from high blood pressure, high cholesterol, diabetes, and heart disease, each of which can be controlled with safe medicines. 2) The mildly overweight don't run these health risks, yet drug companies are using results from 300 pounders to sell drugs to 140 pounders who want to look good at the beach. 3) Even in the seriously obese, we don't know that these drugs really will save more than they kill, because no studies have been done. (Meanwhile, the drug lobby is blocking the FDA from monitoring for bad outcomes after it approves drugs.)

Fen-phen isn't our first go-round with a miracle cure for obesity, and it isn't likely to be our last. In the late '80s, doctors inflated a balloon device in obese patients' stomachs. Because patients couldn't eat nearly as much, they lost weight and kept it off. But some of the balloons deflated and got stuck in the intestines. Only after several people died was the device pulled off the market. The dieters' craving for something to quiet their hunger is almost as great as their craving for food.