NEW YORK (Reuters Health) – In the largest and longest clinical trial to date comparing the effects of selenium supplements versus placebo, daily oral doses of the mineral failed to reduce the incidence of type 2 diabetes and may have increased it.

Because of its anti-oxidant properties, selenium was believed to improve glucose metabolism and protect against diabetes, Dr. Saverio Stranges and colleagues explain in an early release article in the Annals of Internal Medicine, scheduled for print publication in the August 21st issue. However, evidence for such a benefit is inconclusive.

To take a new look at the issue, Dr. Stranges, at the Warwick Medical School in Coventry, UK, and his group analyzed data from the Nutritional Prevention of Cancer (NPC) Trial. New-onset diabetes was a secondary outcome in the randomized, double-blind trial.

The 1202 subjects (almost all white) in their analysis had normal glucose metabolism at the start of the trial when average age was 63 years. Close to 40% were already using vitamin supplements. Participants were randomly assigned to selenium 200 micrograms daily (n = 600) or placebo (n = 602), and followed for an average of 7.7 years.

The cumulative incidence of 12.6 cases of diabetes per 1000 person-years in the selenium group was significantly higher than the 8.4 cases per 1000 person-years in the placebo group (hazard ratio, 1.55), the investigators found. The risk was particularly notable among those with highest baseline selenium levels.

Dr. Stranges’ team notes that the detrimental effect remained higher in the selenium group in analyses stratified by age, gender, body mass index, and smoking status.

"The public health implications of these findings are substantial," epidemiologists at the Johns Hopkins University Bloomberg School of Public Health in Baltimore write in an accompanying editorial. "More than 1% of the US population take selenium supplements," they say, and more than 35% take multi-vitamins that often contain selenium.

According to Dr. Eliseo Guallar and his associates, selenium has a narrow therapeutic range, and 99% of people in the US have dietary intakes of selenium that surpass the Recommended Dietary Allowance. So until high-quality studies establish that the benefits outweigh any risks, they advise that selenium supplements should be avoided.