• 11/11/2004
  • GINA KOLATA
  • New York Times

People who take high doses of vitamin E to improve their health may not be getting any benefits and may, in fact, be slightly increasing their risks of dying earlier, researchers reported yesterday.

The adverse effect was tiny, however, and some experts with no connections to the vitamin industry say they are not convinced it was demonstrated. It emerged only when the researchers pooled the results from 19 clinical trials involving 135,967 participants. That led them to conclude that there were 39 additional deaths per 10,000 people who were taking vitamin E doses exceeding 400 international units a day.

The recommended daily amount of vitamin E is about 20 international units a day, and the dose in a multivitamin pill is about 30 units. People take much higher doses because they believe that at high doses the vitamin acts like a drug, protecting them from disease.

The new study, by Dr. Edgar R. Miller III, an associate professor of medicine and epidemiology at Johns Hopkins University, will be published on Jan. 4 in The Annals of Internal Medicine. Dr. Miller presented the data at the American Heart Association meeting yesterday in New Orleans, and the journal is making the paper available free on its Web site, www.annals.org.

The results, some nutrition experts said, were disconcerting because vitamin E is widely used by people who hope it will act as an antioxidant and prevent heart disease, cancer, Alzheimer’s disease, and even the common cold. In fact, said Dr. William Thies, the vice president for medical and scientific affairs at the Alzheimer’s Association, taking vitamin E has become “part of the standard of care” for Alzheimer’s patients, even in the absence of solid evidence that it helps.

The Council for Responsible Nutrition, an industry group, says the exact number of people who take vitamin E is not known, but the vitamin is among the most popular of all nutritional supplements. In 2003, sales of the vitamin totaled $710 million and it accounted for 11 percent of all vitamin sales, behind multivitamins , B vitamins and vitamin C.

Dr. Miller said he began the study when he was asked to write a chapter on antioxidants and heart disease for a textbook on preventive cardiology. When he looked at data from clinical trials, however, he noticed that many seemed to show that vitamin users had more heart disease, not less.

“The a priori hypothesis would be that antioxidants are protective, but there hasn’t been any evidence of protection and there has been a hint of harm,” he said. But the evidence of harm was weak, so he and his colleagues decided to pool data from 19 studies to get more definitive answers. Their paper, however, failed to convince some statisticians, who noted that it is notoriously difficult to pool data from disparate studies with different populations and weak results.

“They may well be right, but as a statistician I find this paper unpersuasive,” said Dr. David Freedman, a statistician at the University of California at Berkeley. But since there also is no evidence that the vitamin can help, he added, “I personally wouldn’t recommend that you take large doses.”

Dr. James Robins, a Harvard statistician, had a similar reaction.
“They may be right but they somewhat oversold it statistically,” Dr. Robins said. “It is definitely true that there is no evidence that the low dose does anything for you, and a high dose may be bad. I wouldn’t tell anyone to take this stuff, but this is hardly definitive evidence.”

But even a hint of risk should swing scientists’ reasoning, some said. Dr. John Erdman, a professor of nutritional sciences at the University of Illinois at Urbana-Champaign, said doctors and scientists themselves were taking high doses of vitamin E.

“I remember going to meetings where they said, ‘Raise your hands if you’re taking vitamin E.’ An awful lot of people raised their hands.”
Now, he said, “The increase in risk is extremely small, but it appears to be real.”

Dr. Benjamin Caballero, the director of the Center for Human Nutrition at Johns Hopkins Bloomberg School of Public Health, said the study showed the problem with assuming that vitamins at least would do no harm.

“This reaffirms what many have already said,” Dr. Caballero said. “The evidence for supplementing with any vitamin, and particularly vitamin E, is just not there. This idea that people have that even if it does not have any effect, at least it will not hurt, may not be that simple.”

But Dr. John Hathcock, the vice president for scientific and nutritional affairs at the Council for Responsible Nutrition disagrees. He is not convinced by the new study’s conclusion that high doses of vitamin E are risky, Dr. Hathcock says, and he believes there is at least presumptive evidence that it can help.

For the past 15 years he has taken 400 international units of vitamin E a day, he says, and he does not intend to stop.