Once widely considered a panacea for protecting against diseases associated with aging, antioxidant supplementation is increasingly under fire. Earlier this month researchers reported that taking vitamin E at high doses may do more harm than good. Now new research suggests that low–dose antioxidant supplementation is of only limited value.

Supplementation with small doses of vitamin E, vitamin C, beta-carotene, selenium, and zinc did appear to lower the risk of cancer in men. But French researchers concluded that the observed benefits could easily be derived from eating a balanced diet that includes fruits and vegetables.

Findings from the large Supplementation With Antioxidant Vitamins and Minerals study are reported in the Nov. 22 issue of the journal Archives of Internal Medicine.

“Supplementation may be effective in men (and not women) because of their lower baseline status of certain antioxidants, especially beta-carotene,” researcher Serge Hercberg, MD, PhD, and colleagues write. “The present study reinforces the general recommendations of a lifelong diversified diet that includes an abundance of foods rich in antioxidant nutrients.”

Clinical Evidence for Vitamin E

Millions of Americans take vitamin E and other antioxidant nutrients with the belief that they will help them live longer and healthier lives, but the scientific evidence to back up the belief is contradictory.

Recent reviews of studies with vitamin E supplementation in patients with heart disease have not shown vitamin E to be effective in preventing heart attacks. However, observations continue to show that eating fruits, vegetables, and other antioxidant-rich foods, or taking antioxidant supplements can protect against heart disease and certain cancers.

The majority of studies on antioxidants and disease prevention have involved much higher doses of the nutrients than are found in the typical diet. The average U.S. diet, for example, supplies around 10 international units of vitamin E, but disease prevention studies generally involve dosages of 400 IU or higher.

In this study, Hercberg and colleagues investigated whether antioxidant supplementation at levels that more closely mimic the nutrient intake provided by a healthy diet helps prevent cancer or heart disease in middle-aged people.

Roughly 8,000 French women between the ages of 35 and 60, and 5,000 men between the ages of 45 and 60 took part in the study. Participants took either placebo pills or an antioxidant formulation consisting of 120 milligrams of vitamin C, 45 IU of vitamin E, 6 milligrams of beta-carotene, 100 micrograms of selenium, and 20 milligrams of zinc.

After 7.5 years, researchers found no differences between the antioxidant group and the placebo group in terms of heart disease, cancer incidence, or death from all causes. However, when the researchers looked at cancer incidence according to gender, supplementation did appear to protect men but not women from developing cancer. Men were 31% less likely to develop cancer than women.

On average, the men had lower levels of antioxidants in their blood at study entry than did the women, and the researchers conclude that this could explain the difference in protection.

“The ineffectiveness of supplementation in women may be due to their better baseline antioxidant status,” they wrote.

Time to Abandon Antioxidants?

So what do the new studies mean for people still taking mega doses of antioxidants? Johns Hopkins University epidemiology professor Eliseo Juallar, MD, says it is now clear that the practice is of little or no benefit for preventing disease and could be harmful.

Juallar coauthored the widely publicized review presented at an American Heart Association (AHA) meeting earlier this month, finding that high-dose vitamin E supplementation is associated with an increased risk of dying.

The study’s relevance for young, healthy people has been questioned, because the researchers focused on trials involving mostly elderly, chronically ill patients. But the Johns Hopkins researcher says the evidence is clear.

“There is no question that beta-carotene at high doses is harmful, and it is also clear that [high-dose] vitamin E is not protective and might be harmful,” he says.

Juallar contends that taking as little as 400 IU of vitamin E — the most widely sold dosage — may be dangerous. AHA nutrition spokeswoman Alice Lichtenstein, DSc, says it is now obvious that vitamin E supplementation does not protect against heart disease, but the evidence that it is harmful is not completely convincing.

“What we can say is that there do not appear to strong enough data to advise people to take antioxidant vitamins, including vitamin E, to reduce their risk of cardiovascular disease,” she tells WebMD.

By Salynn Boyles, reviewed by Brunilda Nazario, MD

SOURCES: Hercberg, S. Institut National de la Sante et de la Recherche Medicale (INSERM) and Unite de Surveillance et d’Epidemiologie Nutritionnelle, Paris. Eliseo Juallar, MD, DRPH, assistant professor of epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Md. Alice Lichtenstein, D.Sc, senior scientist and director, Cardiovascular Nutrition Laboratory, Tufts University Friedman School of Nutrition. Boston; chair, nutrition committee, American Heart Association. Eidelman et al., Archives of Internal Medicine, July 26, 2004; vol 164: pp 1552-1556. AHA Scientific Sessions 2004, New Orleans, Nov. 7-10, 2004.