Orlistat, the first drug intended to control weight by interfering with the uptake of fat, is under consideration for approval by the FDA, and last week the manufacturer, Hoffmann-La Roche, announced the results of a study described as ““the largest and longest of an obesity drug ever.’’ The study enlisted 892 overweight adults who participated in a standard weight-loss program involving a 1,500- to 1,800-calorie diet and exercise. One in four received a placebo pill, while the rest took one capsule of orlistat before each meal. After a year, of the 591 left, the placebo group had lost an average of about 13 pounds. Those on orlistat lost what a company official described, accurately, as 50 percent more weight. But another way of looking at the same statistic is that, after a year, they lost, on average, an additional 6 1/2 pounds.
Still, that’s an improvement. And some subjects lost as much as 60 pounds on orlistat. In the second year, when the subjects switched to a higher-calorie maintenance diet, they gained back some weight, but those on orlistat gained less; they also had lower blood pressure, blood sugar and cholesterol levels. ““This drug really does lower cardiovascular risk,’’ says one of the study’s authors, John Foreyt, head of behavioral medicine at Baylor University.
But as a way to get thin, orlistat has obvious drawbacks. It works by blocking the action of lipase, a digestive enzyme that breaks down fat (chart), and thus has no apparent effect on the other main source of dietary calories, carbohydrates. It blocks no more than 30 percent of the fat consumed in a given meal. And, since the drug has to be in the digestive tract when the food is consumed, it won’t do much good against between-meal snacks, which are what make many people fat in the first place.
In theory, people could take a pill before a midnight pint of vanilla-caramel fudge, and get 1,200 calories’ worth of fun for only 1,000 calories’ worth of weight gain. But they’ll only do that once, researchers predict, because the fat that doesn’t get absorbed goes right through to the bowel. People who eat much more than about 20 grams of fat at a meal (the equivalent of two tablespoons of mayonnaise) are likely to suffer side effects ranging from cramps to calamitously embarrassing accidents. In fact, some researchers think the real benefit of orlistat came less from directly blocking fat uptake than from punishing people for eating too much fat in the first place. ““You can think of this as a gastric Antabuse,’’ says Thomas Wadden, director of the eating-disorders program at the University of Pennsylvania, referring to the drug that helps control alcoholism by making liquor intolerable. ““This is a drug to change behavior.''
A spokesman for Hoffmann-La Roche, which hopes to bring orlistat to market as a prescription drug this year under the trade name Xenical, says that people can learn their fat tolerance on the drug and avoid the side effects–which he describes as ““more of an inconvenience than a safety problem.’’ The FDA is reviewing data on orlistat’s safety. But given the drug’s relatively modest effects, the secret of losing weight still lies in what goes into your mouth, not what happens to it afterward.
HOW FAT GETS DIGESTED–OR NOT: 1 Triglycerides (fat molecules) enter the intestine.
2 Fat molecules bind with pancreatic lipase enymes. (Orlistat blocks this process by binding with some of the enzymes instead. Thirty percent of the fat molecules are excreted.)
3 Without orlistat, the triglyceride separates into a fatty acid and a monoglyceride, a fat fragment.
4 They bind with the bile acid. The resulting complex (a micelle) carries the fat pieces into the intestinal wall. The fat enters the bloodstream.
SOURCE: HOFFMAN-LA ROCHE, INC.
GNAWING SUSPICION: LESS FAITH IN FIBER FOR 30 YEARS, IT’S BEEN an article of faith that dietary fiber could help prevent cancer of the colon and rectum. The idea–reinforced by early clinical studies and cereal-company advertising–was that the fiber in whole grains, veggies and citrus fruit acted as ““colonic brooms,’’ carrying carcinogens away as it swept through the bowels. Apparently not, says Charles Fuchs of the Dana-Farber Cancer Institute in Boston. After following almost 89,000 women and their eating habits over 16 years, his team concluded last week in The New England Journal of Medicine that there is no connection between dietary fiber and colorectal cancer, which caused some 57,000 deaths in the United States last year.
Doctors emphasize that eating a high-fiber diet still has many health benefits, and that there are other ways for both men and women (they are stricken roughly equally) to avoid colorectal cancer. Like staying away from tobacco, getting more exercise and losing weight. The nutrient folic acid and regular aspirin use might protect you, too. But when it comes to colon cancer, it seems, salvation doesn’t come in a cereal box.
