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