Vitamin E Linked to Higher Death Rates

Touted antioxidant may be harmful in doses of 400 IUs or more

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HealthDay Reporter

WEDNESDAY, Nov. 10, 2004 (HealthDayNews) -- High doses of the antioxidant vitamin E could increase the risk of death, Johns Hopkins researchers have found.

By re-analyzing the data from 19 vitamin E studies over the past decade, the scientists found that a daily dose of 400 IUs or more was linked to a 6 percent increased risk of death.

"People take significant amounts of vitamin E because they have a perception that it will provide some health benefit and that this will help them live longer, but just the opposite could be the case," said study author Dr. Edgar R. Miller, an associate professor of medicine at Johns Hopkins University.

The finding was presented Wednesday at the American Heart Association's scientific sessions in New Orleans, and will be simultaneously published online in the Nov. 10 issue of the Annals of Internal Medicine.

Miller said this study is similar to recent findings that high doses of another antioxidant, beta carotene -- which has been touted as a cancer preventive -- can do more harm than good.

"This is not new. In several large studies, high doses of beta carotene have been shown to increase the risk for lung cancer and death compared to risk in those who took placeboes, but vitamin E has been given a pass," Miller said.

The Hopkins' researchers noted one caveat: Most of the patients in the trials were over age 60 and were not well, so the study's relevance for younger, healthy adults might be limited.

Dean Jones, a professor of medicine at Emory University Hospital in Atlanta, said the new study warrants reconsideration of the amount of vitamin E people should take.

"When I lecture on this, which I have done for years, the textbook standard is that vitamin E is relatively non-toxic in excess, and I have never distinguished between the amounts of 200 IUs, 400 IUs or even 800 IUs, but in the future I will," he said.

However, the Council for Responsible Nutrition (CRN), a Washington, D.C.-based trade association representing the dietary-supplement industry, was sharply critical of the new study.

The study "inappropriately tries to draw conclusions for the whole population based on a combination of studies of people who were already at grave risk with existing diseases, including cancer, heart disease, Alzheimer's, Parkinson's and kidney failure," the council said in a prepared statement.

John Hathcock, the council's vice president for scientific and international affairs, added, "In reviewing the totality of evidence on vitamin E, including all clinical trial data and several large observational studies, CRN agrees with the Institute of Medicine in finding vitamin E supplements safe at levels of at least up to 1,000 mg (1,600 IU) for normal, healthy adults. This meta-analysis provides no convincing evidence to the contrary."

Hopkins' Miller said the reason for the increase in mortality risk needs to be studied further. But it could be that high doses of vitamin E disrupt the natural balance of antioxidants in the body and increase vulnerability to oxidative damage. Previous research has suggested that antioxidants may protect cells from damage to their DNA caused by oxygen molecules called free radicals. Another possibility is that the vitamin's anticoagulant properties interfere with clotting mechanisms, he said.

For the study, Miller and his colleagues used a process called meta-analysis to reevaluate the data from the 19 studies, which involved 135,967 people, sorting information by whether they were taking high or low doses of the vitamin. Nine of the trials tested vitamin E alone and 10 tested it in combination with other vitamins.

Eleven trials involved intake of 400 IUs or more daily, and nine of those trials showed a 6 percent higher death rate among those who took the vitamin, compared to those who took placeboes. The other eight trials involved low-dose use, 200 IUs daily or less, and it was unclear whether the low doses increased a person's risk of death, Miller said.

Jones explained that the antioxidants vitamin E, vitamin C and beta carotene are different from other vitamins. Most vitamins have specific recommended doses based on the function they perform in the body. For instance, the B vitamin folate interacts with certain proteins in the body, so it's known how much folate is needed to saturate these proteins, he said.

But the antioxidant vitamins react chemically to the free radicals in the body. Because doctors can't accurately measure free radicals, a recommended dose of antioxidants is difficult.

Further, while vitamin C is water-soluble and any excess leaves the body via urine, beta carotene and vitamin E are both fat-soluble so any excess accumulates in the fat cell membranes, Jones said.

There is no recommended dose for vitamin E, although current guidelines set a tolerable limit of up to 1,500 IUs per day. On average, Miller said, daily intake of vitamin E through foods is 10 IUs, and multivitamin pills usually contain 30 to 60 IUs of vitamin E. Vitamin E is found in nuts, leafy green vegetables and wheat germ oil.

More information

The National Institutes of Health offers a fact sheet on vitamin E.

SOURCES: Edgar R. Miller, M.D., Ph.D., associate professor, medicine, Johns Hopkins University, Baltimore; Dean Jones, Ph.D., professor, medicine, Emory University School of Medicine, Atlanta; Nov. 10, 2004, Annals of Internal Medicine; Nov. 10, 2004, presentation, American Heart Association's scientific sessions, New Orleans; statement by the Council for Responsible Nutrition, Washington, D.C.

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