Selenium for preventing cancer

Systematic review of prospective observational studies and six randomized controlled trials assessing selenium exposure or selenium supplementation for cancer prevention in adults. The randomized evidence comprised 43,408 participants, 94% men, across the United States, China, Canada, and Puerto Rico, with baseline selenium exposure measured by biomarkers or dietary/supplement intake.

The randomized evidence evaluated oral selenium supplementation in several forms and doses, including selenium yeast 200 µg/day in the main NPCT trial, 400 µg/day in a NPCT sub-study, sodium selenite 0.5 mg/day for 3 years, selenium yeast 200 µg/day for 2 to 4 years, and L-selenomethionine 200 µg/day in SELECT for a median 5.5 years. One SELECT arm tested selenium 200 µg/day combined with vitamin E; comparators were placebo or other non-selenium arms.

Overall, selenium supplements did not provide convincing cancer prevention benefit, and regular supplementation cannot be recommended on current evidence. In SELECT, selenium alone did not reduce prostate cancer risk versus placebo (HR 1.04, 95% CI 0.90 to 1.18) or total cancer incidence (HR 1.01, 95% CI 0.89 to 1.15), and selenium plus vitamin E was similarly null for prostate cancer (HR 1.05, 95% CI 0.91 to 1.20). The NPCT main trial reported lower total cancer incidence (adjusted HR 0.75, 95% CI 0.58 to 0.97) and cancer mortality (adjusted HR 0.59, 95% CI 0.39 to 0.87), but also increased non-melanoma skin cancer (RR 1.27, 95% CI 1.11 to 1.45; adjusted HR 1.17, 95% CI 1.02 to 1.34). Some liver cancer trials reported reductions, including Li 2000 (RR 0.51, 95% CI 0.34 to 0.77), but the review judged the randomized findings inconsistent and not sufficient to support a preventive effect.

The evidence was heterogeneous in populations, baseline selenium status, selenium species, dose, and follow-up duration, which limits comparability across trials. Most randomized participants were men, so applicability to women is limited, and several outcomes had sparse or inconsistent reporting. Observational findings were vulnerable to confounding, bias, and effect modification, and some trials suggested possible adverse effects, including increased non-melanoma skin cancer and diabetes risk signals.