A Feb. 28 article in the Journal of the American Medical Association that claims certain antioxidant supplements may increase mortality used flawed methods to reach its conclusions, according to leading trade associations for the U.S. dietary supplements industry.
Spokespersons for both the Council for Responsible Nutrition and the Natural Products Association condemned the study, which culled data from a large number of medical research trials on the effect of antioxidant supplements and various diseases. The article's authors claimed that beta-carotene, vitamin A and vitamin E may actually increase the risk of death, based on the results from 68 medical trials with more than 230,000 participants.
Overall, the researchers reported finding no correlation between antioxidant use and death rates among adults in all of the random trials they scrutinized. But when they narrowed their original analysis of 68 trials to include only those they determined to have a solid methodology, termed low-bias risk, they found "significant" mortality rates.
Andrew Shao, CRN's vice president of scientific and regulatory affairs, said picking and choosing criteria in that manner makes for an invalid study.
"While meta-analyses can be useful when the included studies are very similar in design and study population, this meta-analysis combined studies that differ vastly from each other in a number of important ways that compromise the results," Shao said in a statement.
Industry leaders also contended that the study is misleading because it based its conclusions mainly on secondary prevention—how an already sick population responded to treatment associated with the supplements.
Most people who take supplements want to maintain their health or fill gaps in their diet, according to Daniel Fabricant, vice president of scientific affairs at NPA. "The majority of the American population is healthy," Fabricant said. "A healthy population is generally not in a preventive trial."
Fabricant also noted that the researchers eliminated 405 trials outright because of zero mortality in the study groups. "It sounds like there was a high bias to begin with," he said.
Shao made a similar criticism. "This meta-analysis appears to be a predetermined conclusion in search of a method to support it."
The researchers concluded that vitamin A appeared to be the worst of the trio of antioxidant supplements, with an increased mortality rate of 16 percent. Beta-carotene followed at 7 percent and vitamin E at 4 percent for increased risk of death. There appeared to be no discernible health hazard involved with vitamin C or selenium. In fact, selenium seemed to reduce mortality when the results of all 68 trials were combined, according to the article.
"Our findings contradict the findings of observational studies, claiming that antioxidants improve health," wrote the study's authors. "Considering that 10 percent to 20 percent of the adult population (80 [million]-160 million people) in North America and Europe may consume the assessed supplements, the public health consequences may be substantial."
Fabricant argued that if the antioxidants had posed such a hazard in the trials, those researchers would have discontinued the tests. That was not the case, he said.
The study's lead author, Dr. Goran Bjelakovic, of the Center for Clinical Intervention Research, Copenhagen University Hospital, deferred comment to another of the article's authors. Dimitrinka Nikolova did not immediately respond to an e-mail query for further comment.
Antioxidants have become increasingly popular due to their perceived health benefits, particularly in possibly preventing some types of cancer. These substances are believed to work as the Homeland Security of the body, protecting cells from damage caused by unstable molecules known as free radicals. Antioxidants interact with and stabilize free radicals, possibly preventing the cellular damage that leads to disease such as cancer.
But the National Cancer Institute reports that evidence from clinical trials in the 1990s were inconclusive on whether or not antioxidants slow or stop the development of cancer.
For example, the Chinese Cancer Prevention Study, published in 1993, showed that a combination of beta-carotene, vitamin E and selenium significantly reduced the incidence of both gastric cancer and cancer overall. Yet, the next year, another cancer-prevention study demonstrated that lung cancer rates of Finnish male smokers increased significantly with beta-carotene, with no discernible effect from vitamin E.
Bjelakovic and colleagues concluded that there might be several reasons for the negative effects of antioxidants. The substances may interfere with the body's natural defense mechanisms, for example.
"Better understanding of mechanisms and actions of antioxidants in relation to a potential disease is needed," the researchers wrote. The meta-analysis only included synthetic antioxidants, and the findings do not include those antioxidant substances found naturally in fruit and vegetables, the authors noted.
The conflicting reports can understandably cause confusion and skepticism among consumers, say industry experts.
Fabricant cautioned consumers to examine the literature on antioxidants and not to rely on the analysis of one study to make a decision.
"Science doesn't always work in sound bites," he said.
Peter Rejcek is a Bailey, Colo.-based freelance writer.
Natural Foods Merchandiser volume XXVIII/number 4/p. 9, 12