Klein · JAMA 2011 · randomized controlled trial · n=34887

Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

Cited 1757 times in the scientific literature.

Level 2 - randomized trial

Large multicenter randomized controlled trial

PubMed 21990298 · doi:10.1001/jama.2011.1437 · record verified 2026-08-26

What was done

In the Selenium and Vitamin E Cancer Prevention Trial (SELECT), 35,533 relatively healthy men aged 50 or older (black men) or 55 or older (all others) with baseline PSA levels of 4.0 ng/mL or lower and non-suspicious digital rectal examinations were randomized across 427 sites in the US, Canada, and Puerto Rico. The primary analysis assessed 34,887 men randomized to one of four daily oral regimens: selenium (200 mcg/d from L-selenomethionine), vitamin E (400 IU/d of all rac-alpha-tocopheryl acetate), both agents, or matched placebos. The primary outcome was incident prostate cancer over long-term follow-up through July 2011.

What was found

With 54,464 additional person-years of follow-up and 521 new cases since the primary report, 620 men in the vitamin E group developed prostate cancer compared with 529 in the placebo group, representing a statistically significant 17% increase in risk (hazard ratio 1.17, 99% CI 1.004 to 1.36, P = .008; absolute increase of 1.6 cases per 1000 person-years). Prostate cancer incidence was not significantly increased in the selenium group (575 cases; HR 1.09, 99% CI 0.93 to 1.27, P = .18; absolute increase 0.8 per 1000 person-years) or the combined selenium plus vitamin E group (555 cases; HR 1.05, 99% CI 0.89 to 1.22, P = .46; absolute increase 0.4 per 1000 person-years).

Why it matters

This large trial demonstrates that routine high-dose vitamin E supplementation does not prevent prostate cancer in healthy men and actually increases cancer risk, arguing strongly against its use for chemoprevention.

Limits

The study tested only one specific formulation and dose of vitamin E (all rac-alpha-tocopheryl acetate at 400 IU/d) and selenium (L-selenomethionine at 200 mcg/d), so findings may not generalize to other doses, forms, or populations with baseline micronutrient deficiencies. The abstract does not report data on prostate cancer grade, disease-specific mortality, or potential biological mechanisms explaining why combining selenium with vitamin E attenuated the risk increase.

Cited by