Selenium supplementation reduced cancer deaths by 51% in low-selenium study population.

SELENIUM SUPPLEMENTATION HALVED CANCER DEATHS IN LOW-SELENIUM POPULATION, Larry Clark, PhD, University of Arizona, reported at an Oct. 2 session of the Council for Responsible Nutrition's annual meeting in Amelia Island, Fla. Clark presented soon-to-be-published results, gathered from 1983 to 1993, of an ongoing Arizona Cancer Center trial cosponsored by the American Institute of Cancer Research, the American Cancer Society and the National Cancer Institute.

The study shows a 51% reduction in overall cancer mortality, a 37% lower incidence of internal malignancies, a 46% reduction in lung cancer, a 63% reduction in prostate cancer and reduction of a "similar magnitude" in the risk of colorectal cancer for subjects living in low-selenium regions who supplemented their diets with 200 mcg selenium daily, Clark said. The U.S. RDA for selenium is 55 mcg for women and 70 mcg for men.

Selenium appears to be a "preventative agent that acts during the promotional or progressive stage of cancer," Clark reported, and treatment effects varied by stage of disease, with high levels of protection in the earlier stages but no effect on metastatic disease.

In addition to supporting treatment effects of selenium, the data are noteworthy in that there is "no convincing evidence of significant adverse health events in long-term supplementation with 200 mcg of selenium," Clark said. This is "a very important point," he noted, "because selenium has a history" of being viewed as a toxic element, "and we certainly had a lot of trouble getting this project funded because of the reviewers' concern about potential toxicity."

The study looked at "about 150 different illness endpoints, and none of them achieved significance as adverse events," Clark stated. An adverse association was shown for breast cancer in the treatment group, he noted, "but that's based only on 12 cases and, fortunately, in the continued follow-up, the magnitude of that [association] has diminished."

The study was spurred by prior geographic research demonstrating an increase of approximately 10% in cancer mortality "for most of the major sites in the low-selenium regions of the U.S.," as well as research showing that low-selenium populations are more likely to develop skin cancer. "There are marked differences in the [geographic] distribution of selenium," Clark explained, and these differences affect the "availability of selenium in foods and thus the selenium status in the population."

Clark noted that the trial used "a nutritional dose of selenium, a dose that you would get if you lived in the Dakotas or Wyoming in the selenium-adequate regions of the country. The agent was given as a high-selenium food rather than a pure compound [and] thus it mimics what people consume" in selenium-adequate regions of the country, he explained.

The researchers randomized approximately 13,000 subjects in low-selenium regions to receive either a supplement of 200 mcg selenium yeast or a placebo of brewer's yeast. Subjects had plasma selenium levels "in the low range" although "certainly not deficient and not as low as you see in Finland or New Zealand," Clark noted. Subjects on treatment took approximately 12 to 18 months to achieve their maximum selenium levels and then "remained relatively constant over time."

Participants were enrolled at seven clinics located throughout the low-selenium areas of the southeastern U.S. At randomization, subjects had an average age of over 60. About 75% of the subject pool was male, reflecting "the high incidence of skin cancer in males relative to females." There were no significant differences between the treatment and placebo groups in distribution of risk factors, Clark said.

Subjects were given a clinical interview every six months to record illnesses and new medications. In addition, the researchers garnered information from death certificates, medical reports, tumor registries and other sources. "I believe we have almost complete ascertainment of illness" in the study population, the researcher stated.

Clark pointed out that the research "really represents seven replications of the same study" because it was conducted at seven separate clinics. "Six out of the seven clinics had lower cancer incidence and cancer mortality, and five out of the seven had lower total cancer mortality," which is "a rather consistent finding," he said. In addition, "looking at the treatment effect by year for the 10 years in which events occurred, cancer incidence was lower in eight of the 10 years [and] mortality, both cancer and all-cause, [was] lower in nine out of the 10 years, again a rather consistent finding."

The ongoing trial was unblinded in February, at which point subjects in the placebo group were offered the opportunity to go on treatment, Clark reported.