New study finds increased risk of dying, though critics say data analysis is flawed

High doses of vitamin E, which millions of people take to protect themselves against heart attacks, Alzheimer’s disease and other ailments, appear to actually increase the overall risk of dying, researchers reported Wednesday.

A new analysis of data from 19 international studies involving nearly 136, 000 people concluded that the overall risk of dying began to increase at the dose in a typical single capsule of vitamin E, and that the more vitamin E people took, the more their risk of death rose. Someone taking 400 international units of vitamin E a day for five years, for example, would face a 5 percent higher risk of dying, the researchers found.

The study found no increased risk from lower doses, particularly at doses of 200 international units or below, and perhaps even a benefit. A typical multivitamin contains between 30 and 60 international units of vitamin E.

Although the study did not examine how high-dose vitamin E might increase the risk for death, other studies have suggested the substance may boost the danger of heart attacks and strokes, perhaps by affecting blood clotting or blocking the beneficial effects of other nutrients, the researchers said.

Whatever the mechanism, the findings indicate that no one should take high doses regularly and that current guidelines for what is considered a safe maximum daily intake should be lowered, the researchers said in a study presented at an American Heart Association meeting in New Orleans.

“A lot of people take vitamins because they believe it will benefit their health in the long term and prolong life,” said Edgar Miller III, an associate professor of medicine at the Johns Hopkins University School of Medicine, who led the research. “But our study shows that use of high-dose vitamin E supplements certainly did not prolong life but was associated with a higher risk of death.”

In recent years, “antioxidant” substances were thought to provide protection against a host of illnesses. Some scientists and nutritionists theorizied that vitamins and other compounds found naturally in many foods might reduce the risk of heart disease, cancer and other illnesses by preventing unstable oxygen molecules known as free radicals from damaging DNA.

That has prompted many Americans to take supplements containing high doses of antioxidants, including vitamin E.

In 2003, Americans spent $710 million on vitamin E, making it the second most popular individual vitamin behind vitamin C, according to the Nutrition Business Journal.

But when researchers have attempted to give antioxidants to prevent disease, the results largely have been disappointing, and, when taken in large quantities, sometimes alarming. Beta carotene in high doses, for example, was found to increase rather than decrease the risk of lung cancer.

The latest study suggests that may be true for vitamin E in high doses as well, experts said.

“This just shows us once again that very high level of individual nutrients can have adverse effects,” said Alice Lichtenstein, a professor of nutrition at Tufts University. She chairs the nutrition committee of the American Heart Association, which in August recommended against antioxidant supplements to reduce the risk of heart disease.

Other researchers, however, questioned the new findings, saying that the analysis was flawed .

“There is a small statistical effect here that they have found, but we don’t believe it’s necessarily an important biological effect,” said Annette Dickinson, president of the Council for Responsible Nutrition, an industry- funded group. “We think they’ve overstated the importance of the findings.”

The study also failed to convince some statisticians, who noted that it was 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 David Freedman, a UC Berkeley statistician. But because there also is no evidence that the vitamin can help, he said, “I personally wouldn’t recommend that you take large doses.”

While there is only weak evidence that antioxidants reduce the risk of cancer, there is strong evidence that vitamin E and vitamin C can reduce the risk of heart and kidney disease, said Ishwarlal Jialal, an antioxidant researcher at UC Davis.

“Vitamin E is clearly an antioxidant and an anti-inflammatory agent, and it’s been shown in some studies to reduce heart disease either alone or in combination with vitamin C,” he said.

The latest study, however, found that the overall death rate appeared to increase, beginning with individuals taking 400 international units per day, Miller and his colleagues reported in a paper that will be published in the Jan. 4, 2005, issue of the Annals of Internal Medicine.

On average, people get about 10 international units of vitamin E from diet, primarily from consuming foods such as corn, nuts, seeds, olives, spinach, asparagus and other green leafy vegetables and vegetable oils. Vitamin E supplement capsules contain anywhere from about 200 to 800 international units.

Federal nutritional guidelines do not recommend vitamin E supplementation but state that doses as high as 1,000 international units per day are safe. Based on the findings, Miller and his colleagues recommended the upper limits be re-evaluated.