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 yesterday.

A new analysis of data from 19 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 30 to 60 international units of Vitamin E.

Although the study did not examine how high-dose Vitamin E might increase the risk of death, other studies have suggested that 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 R. 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."

The findings are the latest in a series of recent findings undermining the theory that "antioxidant" substances may provide powerful protection against a host of illnesses. Evidence had suggested 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, which tracks industry trends.

But when researchers have attempted to give antioxidants to prevent disease, the results largely have been disappointing, and sometimes alarming. Beta carotene, 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, as well, experts said.

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

Other researchers, however, questioned the new findings, saying the analysis was flawed and that other studies have shown a benefit from taking Vitamin E and other antioxidants.

"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."

Maret G. Traber, an Oregon State University researcher who served on a National Academy of Sciences panel that evaluated Vitamin E, agreed. "Vitamin E won't kill you," Traber said. "Everything we know about Vitamin E is that it's incredibly safe."

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 the University of California at 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 people 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. They reached that conclusion by reanalyzing data collected by 19 studies conducted between 1993 and 2004 involving a total of 135,967 patients in North America, Europe and China using a technique known as meta-analysis.

On average, people get about 10 international units of Vitamin E from diet, primarily from consuming foods such as corn, nuts, seeds, olives, asparagus, spinach, other leafy green vegetables, and vegetable oils. But Vitamin E supplement capsules contain anywhere from about 400 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 reevaluated.

"Certainly there's no benefits to high-dose Vitamin E intake, and we did demonstrate harm, so we're not recommending people take high-dose Vitamin E supplementation," Miller said.

Someone taking 400 international units of vitamin E a day for five years would face a higher risk of dying. The study found no increased risk at 200 international units.