Supplements that millions of Americans take to stave off disease and slow the aging process do not boost longevity and appear to actually increase the risk of dying, according to the most comprehensive study of whether popular "antioxidants" help users live longer.
The analysis, which pooled data from 68 studies involving more than 232,000 people, found no evidence that taking beta carotene, Vitamin A or Vitamin E extends life span and, in fact, indicated that the supplements increase the likelihood of dying by about 5 percent. Vitamin C and selenium appeared to have no impact -- either way -- on longevity.
Based on the findings, published in today's issue of the Journal of the American Medical Association, the researchers warned that consumers should be cautious about taking supplements containing the nutrients. At least 150 million Americans regularly take dietary supplements that often include antioxidants.
"The message is: We shouldn't be putting anything in our mouths until we know whether it works," said Christian Gluud of the Copenhagen University Hospital in Denmark, who led the study. "It appears as if these substances may be harmful."
Representatives of the vitamin industry, as well as some other researchers, disputed the findings, criticizing the study for, among other things, including people who were already sick. People tend to take vitamins to stay healthy, they said.
"There's a large body of data that shows that antioxidant supplementation is beneficial," said Andrew Shao of the Council for Responsible Nutrition, an industry group. "The message to the average consumer is: Don't pay attention to this. This doesn't apply to you. You can go ahead and continue taking your antioxidant supplements in addition to the other things you do in your life to stay healthy."
But Gluud and his colleagues defended the findings, saying that the study used careful methods developed by the internationally respected Cochrane Collaboration, an independent nonprofit effort to methodically assess medical claims. The analysis included many large studies involving healthy people, and the increased risk was clear after accounting for factors that could confuse the findings, Gluud said.
"That is what is disturbing," he said.
Other researchers, while noting that vitamins are useful for people who have nutritional deficiencies, said the findings should prompt people to reconsider whether to continue taking megadoses in an effort to live longer.
"This study shows that these products do not prolong life and may actually shorten it," said Paul M. Coates, who directs the Office of Dietary Supplements at the National Institutes of Health. "If you are taking antioxidant supplements, it would be a good idea to review the results of this study, reflect on why you are taking them and what you hope to gain."
The findings do not necessarily apply to antioxidants found naturally in fruits, vegetables and other foods, Gluud and other researchers stressed. But the findings are consistent with evidence suggesting that some nutrients may be harmful at high doses or could interfere with the body's natural defenses, Gluud and other researchers said.
"By taking these supplements, you might be impeding your immune system's ability to fight off disease or risk factors for chronic disease," said Edgar Miller III of Johns Hopkins University, who in 2004 reported similar findings about Vitamin E. "People are taking these supplements with the presumption that they will live longer or better. This shows they are not living longer and in fact may be at higher risk of dying."
Other researchers were cautious about concluding that the substances were dangerous but said the study added to the now large body of evidence indicating that the hoped-for health benefits have not materialized.
"They probably won't kill you, but they're not going to do any good for you if what you want is to live longer," said Donald A. Berry, a professor of biostatistics at the University of Texas M.D. Anderson Cancer Center in Houston.
Antioxidant supplements became a multibillion-dollar business after studies indicated that the substances may promote health by mopping up damaging "free radicals," which are natural byproducts of cellular processes in the body.
But a series of studies testing the benefits of taking antioxidants and other nutritional supplements have been disappointing. Another study released Monday found that consuming garlic does not lower cholesterol. And several studies have even been alarming, indicating, for example, that beta carotene increased rather than decreased the risk of lung cancer among smokers, and that Vitamin E -- touted to prevent heart disease -- appeared to boost the overall risk of death.
Gluud and his colleagues combed the scientific literature for every study published about antioxidants since 1990 and found 68 involving 232,606 people. Among those, the researchers identified 47 trials involving 180,938 subjects that they classified as "low-bias" because they did the best job of eliminating factors that might produce faulty results.
When they analyzed that data, the researchers found that those taking any antioxidant were 5 percent more likely to die than those who were not. With Vitamin E, the risk rose 4 percent; with beta carotene, 7 percent; and with Vitamin A, 16 percent.
Even though the possible increased risk was relatively small, the "public health consequences may be substantial" because of the large number of people taking the substances, the researchers said.
Vitamin C and selenium did not appear to have any effect on the risk of dying. But Gluud said that "the verdict is still out on those two."
Efforts are still underway to assess the value of taking individual antioxidants for specific purposes, including a large federal study that is testing whether Vitamin E and selenium reduce the risk of prostate cancer.