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Are Antioxidants Bad for the Heart?

A new study suggests this might be so

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Updated November 29, 2003

Dateline: August 20, 2001

Researchers from the University of Washington have reported that patients taking antioxidant vitamins in addition to statin and niacin therapy failed to increase their HDL cholesterol (the "good" cholesterol) as much as patients not taking antioxidants. These results, reported in the August 9, 2001 issue of Arteriosclerosis, Thorombosis, and Vascular Biology, are but the latest in a series of disappointing results in trials examining the ability of antioxidants to prevent heart disease.

It has long been believed that antioxidant supplements like vitamins E and C might help slow or even prevent the formation of plaques within coronary arteries. Indeed, several epidemiological studies seem to confirm that antioxidant vitamins can improve outcomes. As a result, millions of individuals (including many doctors) now routinely take vitamin E and C supplements.

Randomized trials have not been kind to antioxidants

During the last two years, a number of randomized trials using antioxidant vitamin supplements have finally been reported, and the results have generally been disappointing. Because of the failure of randomized trials to demonstrate a benefit from taking antioxidants, both the American Heart Association and the Institute of Medicine have released recent statements saying that, while a diet rich in antioxidant vitamins seems prudent, there is insufficient evidence to recommend using supplements of of vitamin C, vitamin E, beta-carotine, selenium, or other antioxidants to prevent heart disease.

The latest study suggests the possibility of harm

The study from the University of Washington, reported last week, brings up the possibility that antioxidant therapy may do more than merely fail to halt the progression of coronary artery disease. This new study suggests the possibility of harm.

In this trial, patients with coronary artery disease who also had low levels of HDL cholesterol were randomly assigned to one of 4 groups: 1) low-dose statin and niacin therapy; 2) low-dose statin and niacin therapy plus a cocktail of antioxidants; 3) a cocktail of antioxidants without statin and niacin, and 4) placebo. The cocktail of antioxidants consisted of vitamin E, vitamin C, beta-carotene, and selenium.  The study results showed that the increase in HDL levels seen in patients receiving statin-niacin therapy was eliminated when they also received the antioxidants. That is, in these patients the antioxidants were potentially harmful.

As it turns out, this "negative" finding is less than statistically perfect. (The finding that antioxidants would reduce HDL levels was not postulated ahead of time by the investigators, but instead was discovered in a routine review of their data, bringing up the possibility that the reported finding was a random data error instead of an actual physiologic phenomenon.) But the primary endpoints of the study also suggest that antioxidants blunt the benefits seen with statin-niacin therapy. (While patients receiving statin-niacin had a 4% reduction in coronary artery blockage, those who received antioxidants in addition to statin-niacin had a 7% increase in blockage. In contrast, those receiving antioxidants alone had a 15% increase in blockage, and those receiving placebo had a 34% increase in blockage.)

The bottom line: this new study seems to validate the unpopular stance on antioxidant supplements taken by both the American Heart Association and the Institute of Medicine.

What to do about antioxidants

DrRich is sorry to say that he must agree with the policy statements of the AHA and the IOM. So far, there is insufficient data from well-designed randomized trials to issue a general recommendation for people to take supplements of the antioxidant vitamins in order to prevent heart disease. Eating lots of fruits and vegetables - in other words, a good diet - seems the most prudent course at the moment.

But are antioxidants actively harmful? Based on data from randomized trials completed to date, it is likely that they are usually not harmful. But it does seem prudent to recommend that - especially if statins and niacin are being used in the attempt to increase HDL levels - either antioxidant supplements should be avoided, or at the very least, HDL levels should be remeasured both with and without antioxidant supplementation, in order to document whether those supplements are blunting the benefits of statin-niacin therapy.

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