What is the role of vitamin E in prostate cancer risk-reduction?

Updated: Oct 11, 2019
  • Author: Mark A Moyad, MD, MPH; Chief Editor: Edward David Kim, MD, FACS  more...
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Vitamin E is a mixture of various antioxidant tocopherols that are particularly effective against unsaturated fatty acids and that protect against oxidative cell membrane damage. It also seems to lower testosterone levels. Vitamin E is a lipid-soluble antioxidant found in vegetable oils, nut oils (eg, almond, cottonseed, safflower, sunflower), hazelnuts, sweet potatoes, whole grains, and leafy vegetables. Gamma tocopherol is the most prevalent form of vitamin E in the diet, whereas alpha tocopherol, found in dietary supplements, is the most biologically available form.

The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study reported a 30-40% decrease in prostate cancer incidence and mortality in men receiving 50 IU of alpha tocopherol daily, compared with placebo. [64] The preventive effect of alpha tocopherol supplementation continued several years post-trial and resulted in lower prostate cancer mortality. [65] The Health Professionals Follow-up Study reported a decreased risk of advanced prostate cancer. In both of these studies, the benefit was identified only in smokers. Studies of gamma tocopherol have shown variable responses.

It should be noted that the risk for some nutrient deficiencies is higher in current smokers than in nonsmokers. This suggests the study of whether improving the status of some primary antioxidant nutrients in smokers would reduce the risk for prostate cancer. Of course, regardless of what such research might determine, the impact of quitting smoking on reduction of all-cause morbidity and mortality should be heavily emphasized over any discussion of potential supplementation. 

The Prostate, Lung, Colorectal, and Ovarian Screening trial (PLCO) studied dietary vitamin E, beta carotene, and vitamin C intake and evaluated prostate cancer risk, but the results did not provide strong evidence for the ingestion of large amounts of antioxidants, either from the diet or from supplements, for the prevention of prostate cancer, although smokers did derive some benefit. This was a questionnaire study, and the doses reported by the participants varied.

The SELECT trial found no protective effect from vitamin E, taken alone or in combination with selenium. Ultimately, SELECT found a significant increase in the risk of prostate cancer in healthy men who took a vitamin E supplement. [57]

To the credit of the SELECT research group, participant follow-up continued (54,464 added person-years), which provided data on outcomes after cessation of dietary supplementation. [66] This follow-up period revealed potential harm from supplement use, and perhaps helped change the perception that dietary supplement use in healthy populations is innocuous.

A significant (P=0.008; hazard ratio [HR]=1.17) increased risk of prostate cancer was found in the vitamin E group, but not in the selenium or combination intervention arm. More concerning was a trend toward increased risk of Gleason 7 or higher disease in the intervention arms compared with the placebo group, although that did not reach statistical significance in any group. The increased risk of prostate cancer with vitamin E began to emerge after only 3 years, and was found to be consistent for low- and high-grade disease types—so conceivably, the risk might have attained statistical significance if the trial had continued for several more years. 

The negative results from SELECT cannot be explained by bias or increased biopsy rates. Rather, they suggest that the dietary supplements themselves are the issue, and the confidence intervals have only continued to narrow with time.

The Physicians' Health Study II (PHSII), a long-term, randomized, controlled trial involving male physicians, found that neither vitamin E nor vitamin C supplementation reduced the risk of prostate cancer or other cancers. [67] The potential for vitamin E supplements to increase the risk of bleeding events (hemorrhagic stroke, HR=1.74; p=0.04) was also observed in this trial. [68]

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