Vitamin E increases prostate cancer risk in middle-aged men relative to placebo: no significant association observed with selenium, either alone or in combination with vitamin E
- Correspondence to Gwen Wyatt
College of Nursing, Michigan State University, 515 W Fee Hall, East Lansing, MI 48824, USA;
Implications for practice and research
■ Clinicians should inform patients that vitamin E significantly increased the risk of prostate cancer among healthy men, and should be avoided.
■ Extended follow-up of common doses of vitamins and supplements may reveal new and critically significant findings.
The lifetime risk for prostate cancer in the USA is currently estimated to be 16%. The objective of this study was to determine the long-term effect of vitamin E and selenium on the risk of prostate cancer in healthy men who had participated in the original selenium and vitamin E Cancer Prevention Trial (SELECT). For the follow up study, a total of 35 533 men from 427 study sites in the USA, Canada and Puerto Rico were included in randomised trials between 2001 and 2004.
This follow-up study included 34 887 men who were randomly assigned to one of four treatment groups for the previous 7–12 years; 8752 received selenium (200 µg/day from L-selenomethionine); 8737 vitamin E (400 IU/day of all rac-α-tocopheryl acetate), 8702 both agents and 8696 placebo. Eligibility criteria for otherwise healthy men included a prostate-specific antigen of 4.0 mg/ml or less, a digital rectal examination not suspicious for prostate cancer, and age 50 years or older for black men and 55 years or older for all others. The primary end point was prostate cancer incidence confirmed by central pathology review. A proportional hazards model was used to compare prostate cancer and other cancer incidence between the placebo group and each of the three study groups with active agents. Men were monitored every 6 months and annually with a limited physical exam. Since the follow-up was unblinded, men in the placebo group were given a multiple vitamin that did not contain either active ingredient in order to facilitate adherence.
The primary analysis included 34 887 men. In the placebo (referent) group, 529 men developed prostate cancer. By comparison to the referent group, 620 (p=0.008) men in the vitamin E group, 575 (p=0.18) in the selenium group and 555 (p=0.46) in the group with both agents developed prostate cancer.
This extension of the SELECT study was well designed, and makes a critical contribution to the long-term effects of a common dose of vitamin E with healthy men. This study provides a clear indication that vitamin E, at this study dose and duration, not only does not protect against prostate cancer, but contributes to its growth among otherwise healthy men. These findings point to the potential harm of supplementing with a common vitamin.
It appears that the search for a prostate cancer protective agent for healthy men remains elusive. Similar to this study, selenium, lycopene and soy have also not shown to reduce the risk of prostate cancer.1 2 However, the findings of the present study are inconsistent with two other contemporary studies. First, the α-tocopherol, β carotene trial reported a 35% risk reduction for prostate cancer among men who were long-term smokers taking 50 mg/day of vitamin E for a median of 6.1 years.3 Second, the Physicians Health Study II (PHSII) found no effect on the incidence of prostate cancer or overall mortality with an every other day dose of 400 IU of vitamin E for a median of 8 years.4 Even though the findings of the present study do not support the two other most prominent studies that tested vitamin E for prostate cancer protective effects, this study provides a clear contraindication to vitamin E that is specific to the average healthy man, using a common daily dose.