Vitamin E is Not the Panacea for This Ill

Abstract & Commentary

By Rahul Gupta, MD, MPH, FACP, Clinical Assistant Professor, West Virginia University School of Medicine, Charleston, WV. Dr. Gupta reports no financial relationships relevant to this field of study.

Synopsis: In a large randomized trial of healthy men, dietary supplementation with vitamin E (400 IU/day) significantly increased the risk of prostate cancer.

Source: Klein EA, et al. Vitamin E and the risk of prostate cancer: The Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2011;306:1549-1556.

In the United States, prostate cancer remains the most common cause of nonskin-related cancer and the second most common cause of cancer deaths in men. Recently, the U.S. Preventive Services Task Force (USPSTF) concluded that the prostate-specific antigen-based screening results in small or no reduction in prostate cancer-specific mortality and is associated with harms related to subsequent evaluation and treatments, some of which may be unnecessary. This panel is recommending that men no longer undergo a prostate-specific antigen test.1 Older men, African American men, and men with a family history of prostate cancer are at increased risk for developing and dying from prostate cancer. We know that even if prostate cancer screening is determined to be effective, the length of time required to experience a mortality benefit is more than 10 years. Because a 75-year-old man has an average life expectancy of about 10 years, very few men age 75 years or older would experience a mortality benefit from an early diagnosis. Similarly, one can argue that men younger than age 75 years who have chronic medical problems and a life expectancy of fewer than 10 years are also unlikely to benefit from screening and treatment. Given the high prevalence of disease, coupled with uncertainties surrounding prostate cancer screening and treatment in men younger than age 75 years, it makes sense to develop an effective prevention strategy that would lead to a significant reduction in incidence of the disease. In the past, preclinical, epidemiological, and Phase 3 data from randomized, placebo-controlled clinical trials have suggested that both selenium and vitamin E have potential efficacy in prostate cancer prevention.2

In the current SELECT study (the Selenium and Vitamin E Cancer Prevention Trial), the authors report studying 35,533 healthy men over the past 10 years, looking at whether vitamin E or selenium would decrease the risk of prostate cancer. These men were randomized at 427 sites from the United States, Canada, and Puerto Rico and placed into four groups, giving them daily oral doses of 1) vitamin E (400 IU/d of all rac-α-tocopheryl acetate), 2) selenium (200 μg/d from L-selenomethionine), 3) vitamin E and selenium, and 4) placebo. Researchers found that compared with the placebo group, in which 529 men developed prostate cancer, 620 men in the vitamin E group (hazard ratio [HR], 1.17; 99% confidence interval [CI], 1.004-1.36, P = 0.008); 575 men in the selenium group (HR, 1.09; 99% CI, 0.93-1.27; P = 0.18), and 555 men in the selenium plus vitamin E group (HR, 1.05; 99% CI, 0.89-1.22, P = 0.46) developed prostate cancer. The absolute increase in risk of prostate cancer per 1000 person-years was noted to be 1.6 for vitamin E, 0.8 for selenium, and 0.4 for the combination as compared with placebo. The researchers noted important strengths in the current study, including the type of population that was included (fewer smokers, prescreened for prostate cancer which was the primary endpoint) that did not exist with other past trials.

The authors also conducted an extended follow-up of SELECT which showed that healthy men with an average risk of prostate cancer who took a common dose and formulation of vitamin E (400 IU/d) were observed to have a 17% increase in prostate cancer incidence.

Commentary

This study finding is the latest in a series of unexpected and disappointing research results demonstrating that high doses of vitamins and other supplements are not only unhelpful in preventing disease conditions, but may actually cause harm. In fact, there has never been any compelling evidence that taking dietary supplements for healthy adults serves any purpose. Most studies of vitamins and supplements have shown no cancer benefits and few similar to the above study have demonstrated harm. In 2007, a meta-analysis of 47 trials involving 181,000 patients showed that the antioxidant supplements significantly increased mortality (relative risk, 1.05; 95% CI, 1.02-1.08).3 Beta carotene, vitamin A, and vitamin E, either singly or combined, were the main culprits to significantly increased mortality. Yet, the supplement industry continues to remain vibrant and largely unregulated making claims that are often not supported by good science. The observed increased incidence for prostate cancer due to vitamin E supplementation demonstrates the potential for seemingly innocuous yet biologically active substances, such as vitamins, to cause harm. It is good clinical practice for physicians to discuss these findings with patients in order to convince those with healthy dietary intake that supplements may no longer be necessary and may even be injurious to their health.

References

1. U.S. Preventive Services Task Force: Screening for prostate cancer. A Review of the Evidence for the U.S. Preventive Services Task Force. October 2011. http://www.uspreventiveservicestaskforce.org/uspstf12/ prostate/prostateart.htm.

2. Klein EA. Selenium and vitamin E cancer prevention trial. Ann N Y Acad Sci 2004;1031:234-241.

3. 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. Review. Erratum in: JAMA 2008;299:765-766.