OBJECTIVE -The purpose of this study was to examine the relationship between serum selenium levels and the prevalence of diabetes among U.S. adults.RESEARCH DESIGN AND METHODS -We conducted a cross-sectional analysis of 8,876 adults Ն20 years of age who participated in the Third National Health and Nutrition Examination Survey. Diabetes was defined as the presence of a fasting plasma glucose Ն126 mg/dl, a self-report of a physician diagnosis of diabetes, or current use of insulin or oral hypoglycemic medication. Serum selenium was measured by atomic absorption spectrometry.RESULTS -Mean serum selenium levels in participants with and without diabetes were 126.5 and 125.7 ng/ml, respectively. Age-, sex-, race-, and BMI-adjusted mean selenium levels were 126.8 ng/ml in participants with diabetes and 124.7 ng/ml in participants without diabetes (adjusted difference 2.1 ng/ml [95% CI 0.4 -3.8]; P ϭ 0.02). The multivariable adjusted odds ratio for diabetes comparing the highest to the lowest quintile of serum selenium was 1.57 [1.16 -2.13]. However, the association between high serum selenium and the prevalence of diabetes was nonlinear, with no clear trend in quintiles 2-4.CONCLUSIONS -In a probability sample of the U.S. population, high serum selenium levels were positively associated with the prevalence of diabetes. Until findings from prospective studies and randomized controlled trials are available, selenium intake, including selenium supplementation, should not be recommended for primary or secondary diabetes prevention in populations with adequate selenium status such as the U.S. population. Diabetes Care 30:829 -834, 2007

In a representative sample of the US population, we found a nonlinear association between serum selenium levels and all-cause and cancer mortality. Increasing serum selenium levels were associated with decreased mortality up to 130 ng/mL. Our study, however, raises the concern that higher serum selenium levels may be associated with increased mortality.

Elevated serum selenium was associated with elevated serum concentrations of total cholesterol, LDL cholesterol, HDL cholesterol, triacylglycerols, apo B, and apo A-I among US adults, a selenium-replete population. Experimental studies are needed to determine cause and effect relations and the potential mechanisms underlying these associations.

Our meta-analysis showed no evidence of a protective effect of antioxidant or B vitamin supplements on the progression of atherosclerosis, thus providing a mechanistic explanation for their lack of effect on clinical cardiovascular events.