Men receiving vitamin E supplements showed a 17% increase in the risk of developing prostate cancer, reports the SELECT study published in the Journal of the American Medical Association. Coming hot on the heels of another study linking dietary supplements to increased mortality in older women (published in the Archives of Internal Medicine on Monday) this week's news could be described as " a bit of a downer" for the supplements industry.

To date preclinical and epidemiological evidence has suggested that selenium and vitamin E might reduce the risk of prostate cancer. In the SELECT trial Eric Klein and colleagues, from the Cleveland Clinic (Ohio, US), undertook a prospective randomised trial to explore the effects of selenium and vitamin E in the prevention of prostate cancer.

Between 2001 and 2004 the SELECT study randomised 35,553 men, aged 50 years and older, to one of four study arms. One group took selenium (n=8752), one took vitamin E (n=8737), one group took both agents (n=8702) and one group took just placebo (n=8696). Participants were then monitored every six months for development of prostate cancer.

Results at seven years showed that in comparison with the placebo reference group where 529 men developed prostate cancer, 620 men in the vitamin E group developed prostate cancer (HR 1.17, P=.008); 575 men in the selenium group (HR 1.09, P=.18) and 555 in the selenium plus vitamin E group (HR 1.05, P=.46). Furthermore, In comparison with placebo, the absolute increase in risk of prostate cancer per 1000 person years was 1.6 for vitamin E, 0.8 for selenium and 0.4 for the combination.

"The lack of benefit from dietary supplementation with vitamin E or other agents with respect to preventing common health conditions and cancers or improving overall survival, and their potential harm, underscore the need for consumers to be sceptical of health claims for unregulated over-the counter products in the absence of strong evidence of benefit demonstrated in trials," conclude the authors.

Taken together with other studies that have previously reported an increased incidence of lung cancer with high-dose beta carotene, and increased risk of colon polyps with high dose folate, they add, suggests "caution" should be used when recommending or studying high doses of micronutrients.

Since there was not a statistically significant increase in the risk of prostate cancer in the vitamin E and selenium combination arm, comment the authors, this suggests that selenium may exert a protective effect by dampening the increase risk associated with vitamin E alone. The biological explanation for the observed increased risk of prostate cancer in the vitamin E arm was not apparent from the data.

The fact that the increased risk of prostate cancer in the vitamin E group of participants was only apparent after extended follow-up, suggests that health effects from these agents may continue even after the intervention has stopped, emphasizing the need for long-term follow-up.

"As opposed to synthetic pharmaceuticals, these naturally occurring dietary constituents are part of normal physiology, and a U-shaped dose response curve may exist where either deficiency or supra-physiological doses are harmful," write the authors.

Reference

E Klein, I Thompson, C Tangen. Vitamin E and the Risk of Prostate Cancer: The selenium and vitamin E cancer prevention trial (SELECT), JAMA 2011; 306: 1549-1556.