Last week's big nutritional news was that taking certain nutritional supplements increases risk of death. Apparently. News headlines throughout the U.K. [and the United States] were awash with the report of a study, which found that the taking of antioxidant nutrients (namely beta-carotene, vitamin A, and vitamin E) in supplement form is associated with a statistically significant increase in risk of dying [1]. The increased risk for vitamin A, beta-carotene, and vitamin E was found to be 16, 7, and 4 percent, respectively.
The study in question was a meta-analysis, where similar studies are lumped together and analyzed in an effort to assess the broad effects of a treatment. Sixty-seven studies were used in the original analysis. These trials were randomized trials, in which individuals were allocated to receive either the nutritional supplement or placebo. These studies were designed to be double-blind, which means efforts were made to ensure that neither the study participants nor the investigators knew who was taking what until the end of the study.
When all relevant studies were included in the analysis, neither vitamin A, beta-carotene, nor vitamin E were associated with either an increased or decreased risk of death. Plus, studies involving selenium showed that taking this nutrient was associated with a 10 percent reduced risk of death.
Not content with leaving it there, however, the authors of this study went on to do some further analysis of the data. Specifically, they culled about a third of the studies if there was evidence of bias. For example, if there was evidence that the double-blind nature of the study was compromised, it was excluded.
It was on the basis of this more focused analysis that the results showing increased mortality came to the fore.
I can understand the authors of this study wanted to use the very best methodology to assess the available data. However, it needs to be borne in mind the 67 studies analyzed by the authors represented only a small part of several hundred studies available for analysis. It turns out that many studies were not deemed suitable for inclusion in the meta-analysis because no one died during the course of the study. I can see no good reason to exclude such studies. One thing is for sure: their presence in the overall analysis would have diluted its negative findings, and may have negated them altogether. It seems that while the authors of this review were concerned about bias regarding the methodology of the studies they analyzed, their methodology for picking studies was somewhat biased from the start.
Another thing to bear in mind is that the studies analyzed in this review were of relatively high doses of nutrients, and in the main, far higher than the sorts of dosages found, say, in a multivitamin and mineral preparation. Another potential deficiency of this analysis is that it focused on studies in which nutrients had been used in their synthetic form, that is, a form not found naturally in food and some supplements.
Another deficiency of the analysis is that it included a bit of a hotchpotch of studies. Ideally, meta-analyses should include studies that have similar protocols, such as duration of treatment and treatment dosage.
However, the studies included were widely different in terms of these things. For example, vitamin E dosages ranged from 10 and 5,000 international units (that's a 500-fold difference), and study periods ranged from four weeks to 14 years.
No piece of science is perfect, but some research is more perfect than others. My opinion is this review's weaknesses and limitations mean that it's hard to draw any conclusions from it. The selective approach to selecting studies, the very variable protocols of the studies, and the fact that the focus was on high doses of synthetic nutrients, means that this review has little or no relevance to individuals taking, say, a multivitamin and mineral each day as nutritional insurance.
Reference:
1. Bjelakovic G, et al. Antioxidant supplements for the prevention of
mortality in healthy participants and patients with various disease
(Review). The Cochrane Library 2008 Issue 2.
Dr. John Briffa is a London-based doctor and author with an interest in nutrition and natural medicine.
Dr. Briffa's Web site
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