Is vitamin E dangerous?

"Vitamin E supplements carry death risk," read the headline from the United Press International news service last November. The Ottawa Citizen in Canada was even more blunt: "High doses of vitamin E can kill you."

What provoked the sudden warning about a supplement that 40 percent of Americans take, usually in their daily multivitamin?

"We were reviewing vitamin E studies for a chapter in a book when we noticed that those taking vitamin E seemed more likely to die than those taking a placebo," says epidemiologist Pete Miller of Johns Hopkins University in Baltimore. "So we decided to do a meta-analysis of vitamin E research."

Unfortunately, Miller's meta-analysis didn't resolve the question of whether vitamin E is safe.

Studying Studies

A meta-analysis combines the data from smaller studies into one large, more powerful study. Pete Miller's included 19 studies on 136,000 men and women who took anywhere from 17 IU to 2,000 IU a day of vitamin E for up to eight years. (1)

When Miller looked only at people who took 400 IU or more, his analysis showed that the death rate was slightly (about four percent) higher than in those who took a placebo. That amounted to an extra 48 deaths for every 10,000 people who were getting the vitamin.

"It didn't matter whether the vitamin E was synthetic or natural, or whether the subjects were healthy adults," says Miller. "The results were the same."

The take-home message? "High-dose vitamin E supplements should be discouraged," Miller and his colleagues concluded.

Others disagree.

"The meta-analysis is flawed," charges Donald Berry, chairman of the Department of Biostatistics and Applied Mathematics at the University of Texas MD Anderson Cancer Center in Houston. In March, Berry was invited by the National Institutes of Health (NIH) to review the meta-analysis for a workshop in Washington.

"The meta-analysis is based on the assumption that the underlying rate of death in all 19 studies is the same," he explains. A more valid approach, in Berry's view, would be to assume that the death rate varied from study to study.

"If you make [that] alternate assumption," he says, "then vitamin E is unlikely to increase mortality at any dose."

"This meta-analysis does not provide a reason to take or not take vitamin E."

Abandon All HOPE

Less than a week after the workshop, new evidence that vitamin E may harm the heart emerged from an international trial.

In the HOPE-TOO study, researchers from 13 countries followed more than 7,000 men and women with cardiovascular disease or diabetes who were given 400 IU a day of vitamin E or a placebo for seven years. (2) The scientists were testing whether the vitamin helped prevent heart attacks, strokes, or cancer. It didn't.

But the vitamin E takers were slightly (13 percent) more likely to suffer heart failure. That translated into 140 additional cases of heart failure for every 10,000 people who took the vitamin.

"In conjunction with its lack of efficacy, the potential for harm suggested by our findings strongly supports the view that vitamin E supplements should not be used in patients with vascular disease or diabetes," the researchers wrote.

But others aren't yet ready to write off vitamin E.

The National Cancer Institute has recruited 35,000 men in North America to test whether vitamin E (400 IU a day) and/or selenium (200 micrograms a day) can prevent prostate cancer over a five-year period. The NCI launched the study because in 1994 researchers found a lower rate of prostate cancer in Finnish smokers who were given 50 IU a day of vitamin E for five to eight years.

And the National Eye Institute is launching a new trial to see if vitamin E, together with lutein and omega-3 fats, can slow the onset of macular degeneration, the leading cause of blindness in older Americans. (Researchers haven't yet determined the dosages.)

Why? In 2001, the institute found that the disease progressed more slowly if people with macular degeneration were given a daily dose of vitamin E (400 IU), beta-carotene (25,000 IU), vitamin C (500 mg), zinc (80 mg), and copper (2 mg).

The Bottom Line

When it comes to preventing heart disease, "vitamin E has been a real bust," says epidemiologist E.R. Greenberg of Dartmouth Medical School in Hanover, New Hampshire. "But whether it's causing measurable harm, I don't know. If it were substantially increasing the risk of congestive heart failure in a wide range of people, researchers would probably have noticed it by now."

"In the absence of any evidence that it's helping and the suggestion that it may be harmful, I would discourage people from taking high doses of vitamin E unless they're participating in a monitored research trial or have been told to take it by their doctor as part of a strategy. to prevent macular degeneration."

Our advice: if you take vitamin E, keep it to no more than 100 IU a day. The same meta-analysis that reported an increased risk of death at 400 IU or more saw no harm at 100 IU. And 50 IU a day decreased the risk of prostate cancer, at least in smokers.

(1) Annals of Internal Medicine 142: 37, 2005,

(2) J. Amer. Med. Assoc. 293: 1338, 2005.