Some Antioxidant Supplements May Raise Death Risk

But critics say the review of the data has serious flaws

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By
HealthDay Reporter

TUESDAY, Feb. 27, 2007 (HealthDay News) -- For years, the word "antioxidant" has been synonymous with disease-fighting goodness for most health-conscious Americans, but too much of the compounds just might be bad for you.

A controversial new review of data from 68 studies concludes that some of the antioxidant supplements that people take to prevent or treat disease might actually increase their risk of death.

The study, published in the Feb. 28 issue of the Journal of the American Medical Association, drew quick criticism from one independent expert.

"One of the major premises of doing such a meta-analysis is that the studies should be comparable," said Jeffrey Blumberg, director of the Antioxidants Research Laboratory at Tufts University in Boston. "Here, they looked at primary prevention, treatment, old people, young people, smokers, nonsmokers. Only when they used their own criteria of what was good and what was bad were they able to show an increase in all-cause mortality."

The study, led by Dr. Goran Bjelakovic of the Center for Clinical Intervention Research at Copenhagen University Hospital, Denmark, covered trials encompassing more than 232,600 participants.

It found no overall increase in death rates when all the trials were considered. But when the trials were divided into classes using the researchers' own criteria, they found an increased risk of mortality associated with beta carotene, vitamin A and vitamin E supplements. No increased risk was found for two other antioxidants, vitamin C and selenium.

"Our findings contradict the findings of observational studies claiming that antioxidants improve health," the researchers wrote. They hypothesized that eliminating free radicals might interfere with a natural defense mechanism and possibly increase the risk of death.

A representative of the supplements industry was not impressed with the study, however.

The mortality risk finding was unwarranted and the study badly flawed, said Andrew Shao, vice president for science and regulatory affairs at the Council for Responsible Nutrition, a trade association representing the dietary supplement industry.

"They included every trial under the sun," Shao said. "Some [studies] were a day long, some were several years long. The majority of trials involved very sick patients -- treatment trials that were very, very different from how antioxidant supplements are used by most consumers, which is to maintain health."

In fact, antioxidants were used to treat a variety of diseases in 47 of the trials used in the study. Those therapeutic trials included more than 68,000 participants. There were another 21 trials, involving more than 114,000 people, where people took antioxidants in hopes of preventing disease.

Even then, "overall, they didn't find a mortality effect," Shao said. "Only when they divided the trials up using their own criteria were they able to come up with this statistically significant effect."

That effect -- an increase of 7 percent in death risk associated with beta carotene supplements, a 16 percent rise associated with vitamin A use, and 4 percent increased risk associated with vitamin E -- was found in trials described as "low-bias," meaning that they met Bjelakovic group's criteria for careful scientific controls.

Blumberg offered some technical criticisms of the study, as well.

The antioxidants in the study have widely different modes of action, he noted. "It's like putting two very different drugs together and drawing one conclusion," Blumberg explained.

In addition, he said, "they do not mention anywhere in the report what people are dying of," so that it is difficult to attribute the deaths to the supplements.

"You don't see people dropping dead right and left from overdoses of antioxidant supplements," Blumberg said. "It is just not happening. You have to explain to me how some essential nutrients kill you in a couple of years."

Antioxidant supplements "have been shown in a number of studies to have no adverse effects," Blumberg said. "They are not toxic, but evidence that they prevent heart disease and cancer is equivocal."

So, in his opinion, it remains "perfectly reasonable" to take a multivitamin. "Whether you take an additional antioxidant depends on how you feel about the evidence," he said.

Both the American Heart Association and the American Cancer Society have said that the evidence for the benefits of antioxidant supplements is inconclusive. Both recommend getting antioxidants from a diet rich in fruits and vegetables.

But some studies have hinted at benefits for specific conditions, Blumberg said. For example, there is some evidence that taking antioxidant supplements may slow the development of neurological problems such as Alzheimer's disease in older people, he said.

The research center that Blumberg heads receives no funding from the supplement industry, Blumberg noted. About 85 percent of its money comes from federal agencies, with the rest given by producers of products such as California oranges.

More information

There's more on antioxidants at the American Heart Association.

SOURCES: Andrew Shao, Ph.D., vice president, science and regulatory affairs, Council for Responsible Nutrition, Washington, D.C.,; Jeffrey Blumberg, Ph.D., director, Antioxidants Research Laboratory, Jean Mayer USDA Human Nutrition Center on Aging, Tufts University, Boston; Feb. 28, 2007, Journal of the American Medical Association

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