Don't bet your heart on these; if stores could only sell supplements that worked, you'd have a hard time finding any of these "heart disease fighters.".

ANTIOXIDANTS

Talk about underachievers. Despite promising early evidence in animals and people, high doses of beta-carotene and vitamin E have repeatedly failed to prevent heart attacks and death from heart disease.

Taking 50 IU to 800 IU of vitamin E a day didn't cut the risk of dying from heart disease in seven major studies that followed more than 81,000 men and women for up to six years. (1) And there's so little evidence for vitamin C that no one's been willing to fund a major heart disease trial.

While vitamin E doesn't help, at least it doesn't hurt. Not so beta-carotene. In eight studies that monitored a total of 138,000 men and women for two to 12 years, those who were given high doses of betacarotene--15 mg to 50 mg (25,000 IU to 83,000 IU)--every day were 10 percent more likely to die from heart disease than similar people who took a placebo. (1)

"The use of vitamin supplements containing that much beta-carotene should be actively discouraged," cautions Marc Penn of the Cleveland Clinic Foundation, who was on the team that examined the eight studies. (There's no need to cut back on sweet potatoes and other foods that contain beta-carotene.)

If you take Lipitor, Pravachol, or other statin drugs plus large doses of the B-vitamin niacin to control your cholesterol, there's another reason to avoid high doses of antioxidants: they may interfere with the drugs. In a three-year trial of 160 patients with heart disease, three percent of those who were given statins plus niacin to raise their HDL ("good") cholesterol and lower their triglycerides suffered a heart attack, stroke, or other "cardiovascular event." (2) The rate jumped to 14 percent in patients who combined the statins and niacin with large daily doses of antioxidants--800 IU of vitamin E, 1,000 mg of vitamin C, and 100 micrograms of selenium.

"Antioxidant vitamins should rarely, if ever, be recommended for cardiovascular protection," concludes the study's lead author, B. Greg Brown of the University of Washington School of Medicine in Seattle.

GARLIC

It's "cholesterol's natural enemy," say the makers of Garlique. Yet according to a U.S. government-sponsored review of the evidence, garlic's effect on cholesterol levels is "unclear." While garlic supplements seem to produce a slight drop in LDL for the first three months, the decline disappears after six months. (3) In fact, the better the design and execution of garlic studies, the less likely they were to detect any benefit, concluded a review by British alternative-medicine scientists in 2000. (4)

In Germany, where much of the early enthusiasm for garlic's cholesterol-busting potential originated, the government no longer allows companies to claim that garlic can lower cholesterol.

GUGGUL

The first good test of this tree-resin extract outside its native India backfired last year. Researchers at the University of Pennsylvania gave 67 men and women with high cholesterol one or two grams a day of a standardized guggul extract called guggulipid. (The manufacturer, Sabinsa Corporation of Piscataway, New Jersey, funded the study.)

Instead of lowering LDL, Sabinsa's guggulipid actually raised it by five percent. (5) And six of the guggul takers (but none of the placebo takers) developed unpleasant rashes that went away only after they stopped taking the supplement.

TOCOTRIENOLS

In early studies by researchers with a financial interest in the outcome, these vitamin E-like compounds, found in rice and other plant foods, seemed to lower LDL in people with high cholesterol. But three larger and longer trials by independent scientists have come up empty. In the most recent one, the tocotrienol formulation used in Evolve, once the leading national brand, had no impact on LDL. (6)

"Tocotrienols don't seem to affect cholesterol levels in people," says Andre Theriault of the University of Hawaii in Honolulu. "Cholesterol is made by the liver and tocotrienols can inhibit that process in test tubes, but it appears that not enough tocotrienols get into the liver when people consume them as supplements."

ISOFLAVONES 

Isoflavones are estrogen-like compounds that are found in soybeans, clover, and some other plants. Eating at least 25 grams of soy protein a day can lower cholesterol, but "there's no definitive experimental evidence to establish that this is due to the isoflavones in soy," says Thomas Clarkson of the Wake Forest University School of Medicine in Winston-Salem, North Carolina.

In fact, isoflavones extracted from soybeans or from red clover have failed in most attempts to lower LDL. According to a recent analysis that pooled the results of 10 studies, the drop in LDL from eating soy protein was unrelated to the amount of isoflavones in the protein. (7)

RED YEAST RICE 

For centuries, people in China have used powdered rice that has been fermented by red yeast to make wine, preserve food, and improve blood circulation. In a 1999 UCLA study that was funded by the company, the Cholestin brand of red yeast rice lowered LDL by an impressive 22 percent in 83 people with high cholesterol levels. (8)

But in 2001, the Food and Drug Administration pursuaded a federal district court to ban Cholestin because the supplement contained the same active ingredients found in the prescription statin drug Mevacor. Cholestin's manufacturer, Nu Skin of Provo, Utah, replaced the red yeast rice with a plant extract called policosanol (see below).

A lab analysis of eight other brands of red yeast rice found that none contained the same mix of cholesterol-lowering ingredients as the original Cholestin. (9)

The bottom line: the only red yeast rice known to lower cholesterol is no longer for sale.

POLICOSANOL

Policosanol (or polycosanol) extracted from sugarcane lowered LDL by 17 to 31 percent in 19 trials involving more than 1,900 people. But 16 of the studies were carried out by just one group of researchers in Havana, Cuba. (The other three were small trials done in Mexico, Argentina, and Chile.) Policosanol has never been tested in good studies in the U.S., Canada, Europe, or Japan.

What's more, the policosanol used in most U.S. supplements (including the reformulated Cholestin--see "Red Yeast Rice") is extracted from beeswax, not sugarcane. Beeswax policosanol hasn't been tested on cholesterol levels.

(1) Lancet 361:2017, 2003.

(2) New England Journal of Medicine 345: 1583, 2001.

(3) www.ahrq.gov/clinic/epcsums/garlicsum. htm.

(4) Annals of Internal Medicine 133: 420, 2000.

(5) Journal of the American Medical Association 290: 765, 2003.

(6) American Journal of Clinical Nutrition 76: 1237, 2002.

(7) European Journal of Clinical Nutrition 57: 940, 2003.

(8) American Journal of Clinical Nutrition 69; 231, 1999.

(9) Journal of Alternative and Complementary Medicine 7: 133, 2001.