Antioxidants: Good Or Bad?
Chester J. Zelasko, Ph.D. | March 2, 2007

Recent health-news headlines reported that antioxidants are not beneficial and may even be hazardous to your health. As a result, our e-mail inbox is full of questions from concerned readers who take antioxidants. What did the study say--are the headlines valid? That’s the topic of this Newsletter.

The Review and Analysis
European researchers examined the mortality rate (how many people died) in randomized clinical trials that tested antioxidant supplements as a method of preventing or treating disease (1). They conducted a systematic review of all the available clinical trials on several scientific databases, evaluating more than 1,200 studies; of those, they chose 68 studies that they determined met the qualifications for well-controlled clinical trials. They used a meta-analysis to determine the relative risk of mortality between those who used antioxidants and those who didn’t in the 68 clinical trials studied.

Their conclusions were that they could not find convincing evidence that antioxidant supplements have beneficial effects on mortality. Further, they felt they had found compelling evidence that beta carotene, vitamin A, and vitamin E seem to increase the risk of death. That conclusion generated the headlines we’ve all read.

Problems
The primary problem with the review study is that it was designed to answer a question that was not the hypothesis of the original studies. In other words, the questions the original researchers asked in most cases were about the effects of antioxidants on specific diseases or conditions--not mortality. For example, one was a study that examined the effects of vitamin E on the building of cartilage (2). In another, researchers examined whether antioxidants will improve fatigue in people with biliary cirrhosis (3). Another examined whether antioxidants reduced the rate of macular degeneration (4). Still another was to examine whether elderly patients who took a multivitamin got more infections over a year than those who did not (5). The focus of the research in those studies was not mortality, but in all cases, a few subjects in the experimental group happened to die. Few studies considered the deaths that happened to occur related to taking antioxidants.

A significant problem with the meta-analysis was that the researchers examined only all-cause mortality. The participants in those studies could have died for reasons completely unrelated to the study; we don’t know because the cause of death was not reported in most cases. For example, a pair of subjects in the antioxidant group could have been hit by a bus. If so, would we conclude that people who take antioxidants are more at risk of getting killed by a bus? Probably not. But if these deaths occur in a small study of only 20 people, the all-cause mortality rate would be 20% among the 10 members of the antioxidant group. That’s a very high mortality rate--and it has nothing whatsoever to do with antioxidants.

We can’t determine reliably the effects of antioxidants on mortality because we don’t know the cause of death. More than anything, that’s the major flaw of the study. The authors acknowledge that, but in the next sentence, they attribute the increased mortality to cancer and heart disease with absolutely no evidence to support that statement!

Careful examination of the studies reveals that of the 47 studies considered the most clinically sound by the authors, the 22 largest studies (accounting for 150,000 subjects) showed no difference in mortality between groups. Of the smaller studies, the difference in mortality was less than 1% between those who did and did not use antioxidants. While it may be statistically significant, it can’t be clinically relevant without knowing why the subjects died.

Bottom Line
This study was an exercise in statistics and mathematics; it’s absolutely meaningless for determining whether it’s safe for you to take antioxidants or not.

The TV series “NUMB3RS” shows how using advanced statistical techniques and mathematics can solve problems--but the correct question must be asked, and the data collected and examined must be relevant. It doesn’t matter what answer you get if you’ve asked the wrong question.

References:
  1. Bjelakovic, G, et al. Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention Systematic Review and Meta-analysis. JAMA. 2007;297:842-857.

  2. Wluka A, et al. Supplementary vitamin E does not affect the loss of cartilage volume in knee osteoarthritis: a two-year double-blind randomized placebo-controlled study. J Rheumatol. 2002;29(12):2585-91.

  3. Prince MI, et al. Oral antioxidant supplementation for fatigue associated with primary biliary cirrhosis: results of a multicentre, randomized, placebo-controlled, cross-over trial. Aliment Pharmacol Ther. 2003;17(1):137-43.

  4. Richer S. Multicenter ophthalmic and nutritional age-related macular degeneration study--part 2: antioxidant intervention and conclusions. Am Optom Assoc. 1996;67(1):30-49.

  5. Avenell, A et al. Effect of multivitamin and multimineral supplements on morbidity from infections in older people (MAVIS trial): pragmatic, controlled trial. BMJ 2005;331:324-329.
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