Lippman · JAMA 2009 · Multicenter, double-blind, randomized, placebo-controlled trial · n=35,533

Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

Cited 2128 times in the scientific literature.

Level 2 - randomized trial

Individual randomized controlled trial

PubMed 19066370 · doi:10.1001/jama.2008.864 · record verified 2026-08-26

What was done

A randomized, double-blind, placebo-controlled phase III trial (SELECT) enrolled 35,533 men across 427 sites in the United States, Canada, and Puerto Rico. Eligible participants were relatively healthy men aged 50 or older (African American men) or 55 or older (all other men) with baseline prostate-specific antigen (PSA) of 4 ng/mL or less and a digital rectal examination not suspicious for prostate cancer. Participants were randomly assigned to 4 groups: oral selenium (200 µg/d from L-selenomethionine) plus vitamin E placebo, vitamin E (400 IU/d of all-rac-alpha-tocopheryl acetate) plus selenium placebo, selenium plus vitamin E, or double placebo. Planned follow-up was 7 to 12 years; primary outcome was prostate cancer, and secondary outcomes included lung, colorectal, and overall primary cancer.

What was found

At a median follow-up of 5.46 years (range, 4.17–7.33 years), prostate cancer hazard ratios (99% CIs) versus placebo (n = 416) were 1.13 (99% CI, 0.95–1.35; n = 473) for vitamin E, 1.04 (99% CI, 0.87–1.24; n = 432) for selenium, and 1.05 (99% CI, 0.88–1.25; n = 437) for selenium plus vitamin E. No statistically significant differences occurred for any other prespecified cancer end points (all P > .15). Statistically nonsignificant increases were observed for prostate cancer in the vitamin E group (P = .06) and type 2 diabetes mellitus in the selenium group (relative risk, 1.07; 99% CI, 0.94–1.22; P = .16), but not in the combination group.

Why it matters

This large trial established that selenium and vitamin E supplementation does not prevent prostate or other primary cancers in healthy men, overturning hypotheses from prior secondary analyses.

Limits

The trial examined only single doses and specific formulations (L-selenomethionine and all-rac-alpha-tocopheryl acetate). Follow-up ended at a median of 5.46 years rather than the planned 7–12 years. Baseline nutritional status and dietary intake levels were not reported in the abstract.

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