FAT Burners.

"Fat Magnet." "Exercise in a Bottle." "Thin-Thin." supplement displays are expanding as rapidly as Americans' waistlines.

And why not? To someone who wants help losing weight doesn't want to chance risky prescription drugs like phen-fen, those displays look awfully appealing--lots of choices, stunning claims, no prescriptions needed, few precautions, (mostly) "natural" ingredients, and (usually) cheaper prices.

But do fat-burners work? And how safe are they? Here's what we know about some of the ingredients top-selling weight-loss supplements.

Hydroxycitric acid 

"Nature's Perfect Diet Ingredient." That's what InterHealth Nutraceuticals of Concord California, calls hydroxycitric acid (HCA), which is added to weight-loss supplements like Burn" and "CitraLean." (Its most economical source is the tropical fruit garcinia cambogia, which has become synonymous with HCA.)

Citric acid is a key player in the process that turns the food we eat into the calories our bodies burn or store as fat. HCA is a modified form of citric acid that "inhibits the enzyme that normally helps convert citric acid to fat," explains John Lowenstein of Brandeis University in Waltham, Massachusetts. That means that HCA may be able to temporarily prevent calories from being stored in bellies, hips, and thighs.

In the 1980s, the pharmaceutical firm Hoffmann-La Roche tried to turn HCA into a drug.

"But we dropped it when we saw toxicities in animals," says company spokesperson Darien Wilson. Among the problems: testicular atrophy (withering). "We never got as far as testing it in humans," adds Wilson.

Trouble in animals may or may not translate into trouble in people. It depends on how much of which form of HCA was used and why it caused atrophy. Even so, it's unsettling that the two largest HCA manufacturers--InterHealth Nutraceuticals (CitriMax) and Sabinsa Corp. (Citrin)--apparently were unaware of HoffmannLa Roche's animal studies.

"I'm really, really surprised," said InterHealth's Susan Shaheen. "I've never heard anybody say anything like that about HCA. Something will need to be done if it truly is toxic, because a lot of people use a lot of it."

Are they wasting their money?

Only two good published studies have tested whether HCA helps people lose weight. (Several other studies combined HCA with different ingredients, so no one knows how much --if any--of the weight loss was due to the HCA.)

In Mexico, 18 obese men and women took 1,500 mg of a garcinia cambogia extract each day and were told to eat a 1,000-to-1,500-calorie diet.[1] After eight weeks, they lost nine pounds, significantly more than the two pounds lost by 17 others who were on the same diet plus a (look-alike but HCA-free) placebo.

But HCA went belly-up last year in a larger and longer study in the U.S. Every day for 12 weeks, 42 obese people took 1,500 mg of the Citrin brand of HCA while 42 other obese people got a placebo.[2] Both groups were told to eat high-fiber diets with only 1,200 calories a day.

After three months, the placebo-takers had lost nine pounds, the HCA-takers seven pounds. Statistically, that's a tie.

"The company that sponsored the research wasn't happy about the outcome," remembers lead researcher Steven Heymsfield of the Obesity Research Center at St. Luke's-Roosevelt Hospital in New York. "I came under a lot of pressure to not make the story as bad as it seems.

"It's still possible that HCA works under certain conditions that we haven't discovered yet, since it does cause weight loss in experimental animals at much higher dosages," notes Heymsfield.

Safety aside, with just two decent human studies that show opposite results, the bottom line is murky.

Chitosan

"You can enjoy fried chicken, pizza, cheeseburgers, even butter and sour cream, and stop worrying about the weight," said the slick TV infomercial this spring for "Fat Trapper," a pill that combines chitosan with plant fiber.

Chitosan (KITE-oh-san) is a dietary-fiber-like substance made from chitin, which forms the hard shells of lobsters, crabs, and other shellfish.

"Chitosan binds to fat and substances that are soluble in fat," explains Jan Wadstein of Natural Nutrition, a Norwegian chitosan manufacturer.

"Companies have been studying its effect in people," he adds, "because humans don't have the enzymes to break down chitosan." That allows it to pass through the intestinal tract, taking some fat along with it.

In a small, unpublished, company-sponsored study in Sweden, Wadstein fed 12 men and women of normal weight half a cup of cream along with 1,000 mg of chitosan. In eight of the people, the chitosan bound eight to 14 percent of the cream's fat, preventing about 50 calories--not very much--from being absorbed. Chitosan had no effect in the other four people.

Three studies (all done in Europe) have looked at whether chitosan alone helps people lose weight. Only one found that it did.

Ten overweight Italian men and women lost an average of nine pounds after taking 2,000 mg of chitosan and eating 1,200 calories a day for four weeks.[3] Ten similar men and women who ate the same diet but got a placebo instead of chitosan shed six pounds.

But smaller amounts of chitosan didn't help overweight people who ate a low-calorie diet for four weeks in an unpublished Swedish trial, or overweight people who didn't diet in a recent not-yet-published British study.

Chitosan-takers did lose an average of ten more pounds than placebotakers in four small Italian studies. But it was mixed with guar gum, a soluble fiber that may have accounted for some or all of the weight loss.

A handful of small studies with inconsistent results is hardly what you'd call a ringing endorsement.

But if you're thinking of taking chitosan anyway, be careful. While it may prevent fat from being absorbed, it can do the same to fat-soluble nutrients like vitamin D, vitamin E, and carotenoids. That's a list you don't want to mess with.

Blood levels of vitamin E dropped quickly and sharply in laboratory rats fed the equivalent of ten to 20 times the human dosage of chitosan for two weeks.[4] And their bones lost calcium and other minerals.

"So far, that hasn't been observed in people,' says Wadstein. But the human studies lasted only four weeks or less--possibly not enough time for deficiencies to develop.

And many of the disease-fighting phytochemicals in plant foods are fat-soluble, which makes them vulnerable to chitosan. Some drugs--including estrogen and contraceptives-are fat-soluble, too.

"These are concerns to be considered very carefully," says Wadstein. "It means you have to take your multivitamins and certain drugs at different times of the day than when you take your chitosan."

And it means that you can't take chitosan indefinitely.

"People should take it for just one or two three-month periods, with a break in between,' says Wadstein.

Tell that to the folks who hawk supplements.

"Just take Fat Trapper before any meal you eat that contains fat," former baseball player Steve Garvey told infomercial viewers earlier this year. "It will be part of your life for the rest of your life."

Conjugated Linoleic Acid 

Conjugated linoleic acid (CLA) is a mixture of polyunsaturated fats that forms in the gut of cattle. It's found in their meat and milk.

"In pigs and cattle and in laboratory rats and mice, CLA can increase the amount of muscle and decrease the amount of fat the animals develop as they grow," says Richard Atkinson of the University of Wisconsin.

Humans should only be so lucky. Atkinson and his colleagues gave 80 very obese volunteers--some of them weighing 400 pounds--capsules with either a placebo or about three grams of CLA a day. All were also put on a diet.

Nine months into the study, when it became clear that the people taking CLA weren't losing any more weight than those taking the placebo, the research was halted. No more tests of CLA on weight loss have been attempted.

"It appears at this point that CLA is unlikely to be effective for inducing weight loss," concludes the University of Wisconsin's Michael Pariza, who discovered CLA.

Where CLA may be useful, he adds, is in helping people put on more muscle and less fat if they regain lost weight. "That appears to be CLA's greatest potential."

Other Fat Burners

* Ephedrine. "There's strong evidence that the use of ephedrine leads to weight loss," notes Steven Heymsfield. The amphetamine-like substance, which is derived from the Chinese herb ephedra (ma huang), is found in weight-loss supplements like Diet Fuel and Metabolife.

"When I contrast the evidence for HCA to that for ephedrine, it's nightand day," adds Heymsfield, who has tested both. "But I can't believe that ephedra is still sold over-the-counter." The Food and Drug Administration has received more than 800 reports linking the herb to everything from dizziness, headaches, and chest pain to psychosis, seizures, and strokes. About three dozen deaths have been linked to ephedra.

* Pyruvate. Pyruvate, which is made by our bodies and found naturally in food, is the major ingredient in products like Exercise in a Bottle and Pyruvate Punch.

Here's how the "Reach4Life" web site (www.reach41ife.com) boasts about its Provate I Weight Management Formula: "Pyruvate supplementation has been shown to contribute to a 48% greater rate of fat loss and a 3 7% greater rate of weight loss over nonpyruvate users in clinical studies."

What Reach4Life doesn't tell its customers is that the people in the study it's talking about--who were on 1,800-calorie diets--took 30 grams (the equivalent of half a bottle) of pyruvate a day yet lost only 3 1/2 pounds more than dieters who took a placebo.[5] The retail cost of that much pyruvate: $300 a month.

Would pyruvate work for nondieters or for people taking less than half a bottle a day? Nobody knows.

* Cellasene. Can a little red pill banish cellulite, the spongy fat deposits that make millions of women hate their thighs? That's what Rexall Sundown of Boca Raton, Florida, claimed in a big media splash this spring for a mixture of herbs, lecithin, and fish oil called Cellasene.

So far, only one study has tested Cellasene against a placebo. It hasn't been published in a peer-reviewed journal, so you have to take Rexall's word for what it supposedly showed: the thighs of the 25 women who took Cellasene for eight weeks dropped two-thirds of an inch in circumference--a half inch more than the drop in the thighs of the 15 women who took a placebo. But the study didn't measure changes in the appearance of their skin--which is what bothers women most about cellulite.

Rexall Sundown has promised to do a larger and better study this summer. Meanwhile, if you want to take Cellasene you'll have to shell out about $275 for the first two months and $90 for the second two months.

[1] Invest. Med. Intern. 22: 97, 1995.

[2]) J. Amer. Med. Assoc. 280:1596, 1998.

[3] Acta Toxicol. Ther. 17: 303, 1996.

[4] Biosci. Biotech. Biochem. 59:1211, 1995.

[5] Amer. J. Clin. Nutr. 56: 630, 1992.