The study is being simultaneously released on the website of the Annals of Internal Medicine.
In animal and observational studies, vitamin E supplementation was shown to prevent cardiovascular disease and cancer. However, other studies suggested that high doses could be harmful.
To determine if there is a "dose response," researchers examined different doses of vitamin E supplements and risk of death from any cause. They studied death rates in published clinical trials comparing vitamin E supplementation to placebo and included findings from 14 studies, from 1993 to 2004. Doses ranged from 15 to 2000 IU/day, and average intake was about 400 IU a day.
"Increasing doses of vitamin E were linked to an increase in death," said lead author Edgar R. Miller, M.D., Ph.D., associate professor of medicine at Johns Hopkins University in Baltimore, Md.
According to the analysis, there is no increased risk of death with a dose of 200 IU per day or less, and there may even be some benefit. However, an increased risk was found at amounts above 200 IU per day and significant risk of death was found starting at 400 IU a day. Those who take greater than 400 IU of vitamin E a day are about 10 percent more likely to die than those who do not, researchers said. "Many people who take vitamin E supplements take between 400 and 800 IU in a single capsule," said Miller.
The confusion for many, said Miller, is that some doctors have recommended vitamin E supplementation based on studies suggesting that it is beneficial for specific illnesses. One study in people with a history of prior heart attack showed that vitamin E use correlated with a lower risk of having a second event. In another trial, patients with end-stage kidney disease seemed to benefit. However, in both of these studies (in fact, in seven of the eight high-dose vitamin E trials in this analysis) the patients on vitamin E supplementation were more likely to die than those in the placebo group.
"Typically, we get about 6-10 IU per day of vitamin E in our diets. Vegetable oils, nuts and green leafy vegetables are the main dietary sources of vitamin E. Supplementation can increase intake by 100-fold," said Miller.
Researchers said the current U.S. dietary guidelines do not recommend vitamin E supplementation, but indicate that the upper tolerable limit of intake is 1000 IU per day.
These findings parallel the findings of beta carotene supplementation trials. Two major studies showed that beta carotene supplementation results in an increased risk for lung cancer and death. And, as a result, you will never see beta carotene supplements recommended again," he said.
There is room for more research, however, on the effects of 200 IU or less per day of vitamin E and how low doses taken in combination with other vitamins might positively affect death rates, he said.
"The big questions that need to be answered are: What is the dose? And how low a dose - in what combination - would be most useful?" Miller said.
Co authors are Roberto Pastor-Barriuso Ph.D.; Darshan Dalal M.D., M.P.H.; Rudolph A. Riemersma Ph.D.; Lawrence J. Appel M.D., M.P.H. and Eliseo Guallar M.D., Dr.P.H.
Statements and conclusions of study authors that are published in the American Heart Association scientific journals are solely those of the study authors and do not necessarily reflect association policy or position. The American Heart Association makes no representation or warranty as to their accuracy or reliability.
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