In a trial that included about 35,000 men, those who were randomized to receive daily supplementation with vitamin E had a significantly increased risk of prostate cancer. The authors called the implications of the finding “substantial.”
In background information in the article, which appears in the Oct. 12 issue of the Journal of the American Medical Association, the authors noted “there has been considerable preclinical and epidemiological evidence that selenium and vitamin E may reduce prostate cancer risk.
“The initial  report of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) found no reduction in risk of prostate cancer with either selenium or vitamin E supplements but a statistically non-significant increase in prostate cancer risk with vitamin E. Longer follow-up and more prostate cancer events provide further insight into the relationship of vitamin E and prostate cancer.”
Eric A. Klein, MD, of the Cleveland Clinic, and colleagues examined the long-term effect of vitamin E and selenium on risk of prostate cancer in relatively healthy men. The primary analysis included 34,887 men who were randomly assigned to one of four treatment groups: 8,752 to receive selenium (200 micrograms/day); 8,737, vitamin E (400 IU/day); 8,702, both agents; and 8,696, placebo, with a planned follow-up of between seven and 12 years.
Since the 2008 report, a total of 521 additional prostate cancers have been diagnosed: 113 in the placebo group, 147 in the vitamin E group, 143 in the selenium group and 118 in the combination group. The researchers found that the rate of prostate cancer detection was greater in all treatment groups when compared with placebo but was statistically significant only in the vitamin E alone group a 17% increased rate of prostate cancer detection.
Compared with the placebo group, in which 529 men developed prostate cancer, 620 men in the vitamin E group developed prostate cancer, as did 575 in the selenium group and 555 in the selenium plus vitamin E group. The difference in rates of prostate cancer between vitamin E and placebo became apparent during the participants’ third year in the trial. The elevated risk estimate for vitamin E was consistent across both low- and high-grade disease.
“In this article, we report an observation of important public health concern that has emerged with continued follow-up of SELECT participants,” the authors wrote. “Given that more than 50% of individuals 60 years or older are taking supplements containing vitamin E and that 23% of them are taking at least 400 IU/d despite a recommended daily dietary allowance of only 22.4 IU for adult men, the implications of our observations are substantial.”
The fact that the increased risk of prostate cancer in the vitamin E group was apparent only after extended follow-up suggests that health effects from these agents may continue even after the intervention is stopped, the researchers noted, emphasizing the need for long-term follow-up. They added that the findings of this and other studies illustrate the importance of large-scale, population-based, randomized trials in accurately assessing the benefits and harms of micronutrients as dietary supplements.
“The observed 17% increase in prostate cancer incidence demonstrates the potential for seemingly innocuous yet biologically active substances such as vitamins to cause harm,” the authors wrote. “The lack of benefit from dietary supplementation with vitamin E or other agents with respect to preventing common health conditions and cancers or improving survival, and their potential harm, underscore the need for consumers to be skeptical of health claims for unregulated over-the-counter products in the absence of strong evidence of benefit demonstrated in clinical trials.”
UPDATE: The Council for Responsible Nutrition, which describes itself as the leading association representing the dietary supplement industry, responded to the study.
The study evidences the risks of examining a nutrient in isolation. Duffy MacKay, ND, vice president of scientific and regulatory affairs for CRN, said in a written statement. Interestingly, when vitamin E was combined with selenium, the risk was reduced to a non-significant statistic, perhaps even the result of chance. This reinforces the theory that vitamins work synergistically and that drug-like trials of nutrients, when used in isolation from other nutrients, may not be the most appropriate way to study them.
Because the results of this study are different from other studies, they are not a reason for men to stop using their vitamin E. The authors acknowledge other research has demonstrated the benefits of vitamin E for Alzheimers disease and age-related macular degeneration.
MacKay also wrote that even regarding prostate cancer, the researchers cited a study that demonstrated a 35% risk reduction for prostate cancer in men taking 75 IU vitamin E daily for six years, and another study that resulted in no effect on risk.
Even taking the results of this SELECT research at face value, although statistically significant to a statistician, one wonders if an absolute increase in the risk of prostate cancer of 1.6 cases per 1,000 person-years is really a significantly increased risk of prostate cancer’ as noted in the article, MacKay wrote.