Study findings published in the Journal of the American Medical Association report that supplements of vitamins A and E, and beta-carotene may increase the risk of death by up to 16 percent.
Vitamin C did not have an effect on mortality, while selenium was associated with a 9 percent lower risk of death.
The pooled analysis (called a meta-analysis) of 68 randomized trials used beta-carotene doses ranging from 1.2 to 50 milligrams, vitamin A from 1333 to 200 000 International Units, vitamin C from 60 to 2000 mg, vitamin E from 10 to 5000 IU, and selenium from 20 to 200 micrograms.
In 47 of the 68 trials classified as low-bias (a total of 180,938 participants), overall antioxidant supplement use was associated with a five per cent increased risk of mortality. When the reviewers classified vitamin A intake as "given singly or in combination with other antioxidants supplements" use of the vitamin was associated with a 16 per cent increased risk of mortality.
Beta carotene and vitamin E was linked with seven and four per cent greater risk of death, respectively, whereas there was no increased mortality risk associated with vitamin C, and selenium use was associated with a nine per cent decreased risk.
The study has drawn criticism from both inside and outside the dietary supplements industry concerning the methodology applied, and the conclusions drawn. The Canadian Health Food Association has questioned the findings because the researchers ignored a large body of scientific evidence supporting the benefits of antioxidants when drawing their conclusions.
The most prevalent criticism of the study has come from the diverse nature of the studies pooled together, described by one industry expert as comparing "apples and oranges". The combined studies were far too diverse and different in terms of supplement dosage, duration of use, study population and nutrients tested.
Additionally, most of the trials included in the meta-analysis tested for secondary prevention, looking at how a nutrient works in diseased populations, instead of primary prevention studies in healthy populations. Most of the studies included in the report enrolled subjects already classified as suffering from certain diseases. Indeed, only two of the studies classified as "low bias" were carried out in the 'general healthy population'.
"Combining secondary prevention and primary prevention trials and then making conclusions for the entire population is an unsound scientific approach," said Andrew Shao, Ph.D., Vice President of the US-based Council for Responsible Nutrition. "Additionally, many of the trials had limitations, including the expectation that a simple antioxidant vitamin could be expected to overturn serious illness, such as cancer or heart disease. These trials likely statistically skewed the results."
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