Second thoughts about antioxidants - includes related article

Harvard Health Letter, Feb, 1995 by Larry Husten

The sun has been shining brightly on the antioxidant vitamins. A parade of reports has trumpeted these nutrients - vitamin C, beta carotene, and vitamin E - as stalwarts in the fight against heart disease and cancer.

Now the weather forecast has been modified by recent studies suggesting that these vitamins, when taken as supplements, might not only lack benefit but may also carry the possibility of slight harm. Although it's too soon to say if the antioxidant parade will be rained out, there's no doubt that a cloud of skepticism hovers overhead.

April showers

The wind began to shift in April 1994, when results of the Alpha-Tocopherol, Beta Carotene Cancer Prevention Study (ATBC) were published in the New England Journal of Medicine. In this highly publicized trial, nearly 30,000 male Finnish smokers were randomly assigned to take a daily dose of either alpha-tocopherol (vitamin E, 50 mg), beta carotene (20 mg), both, or neither for 5-8 years. The impetus for the study came from epidemiologic evidence that people who ate more antioxidant-rich vegetables were less likely to develop cancer, especially of the lungs. The ATBC set out to determine whether supplements of these same vitamins could protect against lung cancer and other malignancies as well.

The researchers - not to mention droves of consumers optimistically taking supplements - were surprised to see that vitamin E had no effect on the occurrence of lung cancer. Even more disturbing was the finding that men who took beta carotene showed a slight but statistically significant increase in risk for the disease.

When the investigators turned their attention to overall death rates and to the occurrence of cardiovascular problems, they found that vitamin E had no apparent effect on total mortality. Although participants who took this vitamin were less likely to die of thrombotic strokes (caused by blood clots) than those in the other experimental groups, they were more prone to fatal hemorrhagic strokes (due to bleeding in the brain). Overall mortality was 8% higher in the beta carotene group than for the groups taking vitamin E or no supplements at all, primarily due to more deaths from lung cancer and coronary heart disease. All in all, the study was a major disappointment for people who had hoped that bottled antioxidants would keep them healthy.

Summer doldrums

Only a few months after the Finnish results came out, the New England Journal of Medicine carried another report that shook the confidence of antioxidant boosters. This time the subject was colorectal polyps, which in earlier epidemiologic studies appeared less frequently among people who consumed lots of fruits and vegetables than in those who shunned these foods. Although this association surfaced repeatedly, scientists weren't sure whether protection arose from antioxidant vitamins in the fruits and vegetables, from other constituents of these foods, or from the simple fact that people who fill up on fruits and vegetables won't have room for foods rich in saturated fats and possible carcinogens.

The Polyp Prevention Study Group, led by Dartmouth epidemiologist E. Robert Greenberg, tested the ability of antioxidant supplements to block the formation of colorectal adenomas, polyps that are precursors to invasive colorectal cancer. In this trial, 751 people with a history of colon polyps were assigned to one of four regimens: beta carotene only, vitamins C and E, all three vitamins, or a placebo. After four years, the researchers found that the antioxidant supplements had no effect whatsoever on polyp formation. Although they noted that such pills might yet prove to have an anticancer effect, the investigators said it was likely that "other dietary factors" explain the reduction in cancer risk associated with a diet rich in fruits and vegetables.

Results such as these come as no surprise to hematologist Victor Herbert, who has been trying to dampen enthusiasm for the antioxidant parade for several years. The potential dangers of these supplements are often underestimated, according to Dr. Herbert, a professor of medicine at Mt. Sinai School of Medicine in New York. He claims, for instance, that vitamin C supplements can become "violently prooxidant" in the presence of high iron stores in the body, a condition that he says occurs in "more than 10% of American whites and perhaps as many as 30% of American blacks." Dr. Herbert also points to the unexpectedly high number of hemorrhagic strokes among vitamin E users in the ATBC study as evidence that this vitamin interferes with normal blood clotting when taken as a supplement.

The silver lining

Many scientists believe that it's too early to toss vitamin supplements in the trash, although some people probably have been tempted to do so. In an editorial that accompanied the Finnish report in the New England Journal of Medicine, three leading epidemiologists advised that "the results of the ATBC trial should not . . . be seen as proving these vitamins to be ineffective or even hazardous."