Selenium supplementation might predispose some people to diabetes if they already have adequate levels of the metal, the author of a review cautioned.

Although an adequate selenium status confers multiple health benefits, the potential risks of unnecessary or inappropriate supplementation should not be discounted, according to an article published online in The Lancet.

“The crucial factor that needs to be emphasized with regard to the health effects of selenium is the inextricable U-shaped link with status,” Margaret P. Rayman, DPhil, of the University of Surrey in Guildford, England, wrote. “Whereas additional selenium intake may benefit people with low status, those with adequate-to-high status might be affected adversely and should not take selenium supplements.”

For more than a decade, evidence suggesting beneficial health effects of an optimal selenium status has fueled an “excessive zeal” for selenium supplementation, ending in adverse consequences for some people. The potential for harm should direct attention back to the initial recognition of selenium as a toxic element, Rayman wrote.

Much of the evidence on potential harms has centered on type 2 diabetes. Data from the National Health and Nutrition Examination Surveys showed an association between high selenium levels and an increased risk of type 2 diabetes (Diabetes Care 2007; 30: 829-834, Environ Health Perspect 2009; 117: 1409-1413).

A smaller French study demonstrated a positive association between baseline and follow-up plasma selenium and fasting plasma glucose (Am J Clin Nutr 2006; 84: 395-399).

Mixed results have come from randomized trials wherein type 2 diabetes was a secondary outcome. Similarly, conflicting evidence has come from studies of the relationship between selenium status and glucose metabolism.

Some studies have implicated specific selenoproteins in the association with type 2 diabetes, Rayman wrote. Studies involving animal models have shown that both low-level and high-level expression of certain stress-associated selenoproteins have similar adverse effects on insulin resistance and hyperglycemia.

“Hence, a U-shaped association between selenoproteins and type 2 diabetes risk might explain some of the apparently contradictory findings,” she wrote.

In a previous review, Rayman focused on the emergence of evidence supporting the health benefits of selenium and referred to planned and ongoing clinical trials designed to evaluate the benefits (Lancet 2000; 356: 233-241).

In the current update, she reviewed outcomes of key trials and the current evidence regarding the potential benefits of selenium.

With regard to mortality, results from several large cohort studies have been mixed but generally supported an association between adequate selenium and a reduced mortality risk. Rayman noted that such studies are fraught with potential confounders that leave the results open to a variety of plausible explanations.