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RE: Lessons from the selenium and vitamin E cancer prevention trial (SELECT)

(Accepted 26 March 2009) If the Selenium and Vitamin E Cancer Prevention Trial (SELECT) demonstrated anything, it is that the long-term supplementation of vitamin E at pharmacological dosages is ineffective for cancer prevention and possibly even promotes prostate cancer development. As to selenium, its cancer-preventative effect may not have been seen because the participants were enrolled without consideration of their baseline selenium status. From the measured serum selenium levels on enrollment of 122.4–151.8 ng/mL, their basal selenium intakes reached 200–250 μg/day, and thus even in the placebo group were already close to, or within, the range of 200–300 μg/day, previously estimated as optimal for cancer risk reduction. This may have caused any additional protective effects of supplemental selenium to become unobservable under the conditions of the trial. There is also an issue with regard to the form of selenium chosen. In the SELECT Trial synthetic selenomethionine (Se-Met) was used, and in the Nutritional Prevention of Cancer Trial (NPC) it was selenium yeast, in which the Se-met was protein-bound, which causes the Se-Met to be better protected from oxidation than when exposed to air in the pure state. Ingestion of selenium as pure Se-Met, furthermore, may alter its uptake, excretion, tissue distribution, transport, and metabolism as compared to when it is provided in a protein-bound form that is similar to its normal presence in foods. The failure of SELECT to reduce prostate cancer incidence is in accordance with the results of a recent study, revealing an inverse association of serum selenium vs. cancer mortality only up to serum selenium levels (130 ng/mL). The additional 200 μg of supplemental selenium per day given to the participants of SELECT increased their serum selenium levels to >130 ng/mL and thus rendered the cancer-protective effects of selenium unobservable against the placebo group. Conversely, in the Nutritional Prevention of Cancer Trial (NPC), a significant protective effect of selenium against prostate cancer development was seen because the participants were specifically selected from low-selenium regions of the United States. The inconclusive outcome of SELECT with respect to selenium thus should not be interpreted to suggest a general ineffectiveness of selenium in cancer prevention.