Antioxidant Selenium Offers No Heart-Disease Protection

Selenium does not protect against cardiovascular disease, despite its documented antioxidant and chemopreventive properties, analysis of a randomized placebo-controlled clinical trial covering 13 years has shown.

The selenium-CVD association was a secondary endpoint in the Nutritional Prevention of Cancer Trial, which was designed primarily to determine if selenium supplementation could prevent the recurrence of non-melanoma skin cancer.

Results of the trial, the only large randomized clinical trial to date to examine selenium supplementation alone in the prevention of CVD, appear in the April 15 issue of the American Journal of Epidemiology. Saverio Stranges, M.D., Ph.D., assistant professor of social and preventive medicine in the School of Public Health and Health Professions, University at Buffalo, is first author.

“Our results extend previous research based on smaller intervention trials focusing on cardiovascular risk factors,” said Stranges. “Our findings are consistent with those from previous studies that have shown no beneficial effect of selenium supplementation in combination with other antioxidants on the primary prevention of cardiovascular disease.”

Several antioxidants, vitamins C and E in particular, that were thought to play a role in preventing heart disease based on observational studies have turned out not to be protective in randomized clinical trials, and selenium now has joined this group.

The main findings of this report focus on the 1,004 participants in the study, conducted from 1983-96, who were free of cardiovascular disease when they were recruited. Participants came from seven dermatology clinics in low selenium areas of the eastern United States: Augusta and Macon, Ga.; Columbia, S.C.; Miami, Fla.; Wilson and Greenville, N. C.; and Newington, Conn.

Enrollees were assigned randomly to take a tablet containing 200 micrograms of selenium daily or a placebo. Information on sociodemographics, health habits, education and body mass index also was collected.

Participants provided blood samples at their respective clinics twice a year and reported any new illnesses or medications. Individuals were followed for an average of 7.6 years.

Results showed no association between selenium supplementation on any of the endpoints studied: coronary heart disease, stroke or deaths from cardiovascular disease, Stranges said. There also was no difference in the endpoints based on the level of selenium at baseline. In addition, the lack of significant association with CVD endpoints was confirmed even in the 246 participants who had CVD at baseline. (This data does not appear in the published manuscript.)

“These results must be interpreted cautiously,” said Stranges, “because they result from exploratory analyses, although from the largest randomized clinical trial available that has selenium only as the intervention. However, this report adds important information to our knowledge on the role of selenium in cardiovascular-disease prevention, indicating no overall benefit of supplementation by selenium alone in prevention of cardiovascular disease.”

Additional contributors to the study were James R. Marshal, Ph.D., Raj Natarajan and Mary E. Reid, Ph.D., from Roswell Park Cancer Institute in Buffalo; Maurizio Trevisan, M.D., and Richard P. Donahue, M.P.H., Ph.D., of the UB School of Public Health and Health Professions; Gerald F. Combs, Jr., Ph.D., from the USDA Human Nutrition Research Center in Grand Forks, N.D.; Eduardo Farinaro, M.D., of “Federico II” University of Naples Medical School, Naples, Italy, and the late Larry C. Clark, M.P.H., Ph.D., a major contributor to research on selenium and prostate cancer.

The University at Buffalo is a premier research-intensive public university, the largest and most comprehensive campus in the State University of New York.