Selenium status and cardiovascular diseases: meta-analysis of prospective observational studies and randomized controlled trials

BACKGROUND/OBJECTIVES: Selenium was thought to have a role in cardiovascular disease (CVD) owing to its antioxidant properties; however, evidence from observational studies and randomized controlled trials (RCTs) has been inconsistent and controversial. We thus conducted a meta-analysis to assess the discrepancies between observational and randomized trial evidence. SUBJECTS/METHODS: We searched MEDLINE and EMBASE for eligible prospective studies regarding the relationship between selenium and CVD up to 15 December 2013 and finally included 16 prospective observational studies and 16 RCTs. Random effects model was used to estimate the pooled relative risk (RR). Generalized least-squares trend test and restricted cubic spline model were performed to assess a linear and a nonlinear dose-response relationship. RESULTS: Our meta-analysis of prospective studies showed a nonlinear relationship of CVD risk with blood selenium concentrations across a range of 30-165 mu g/l and a significant benefit of CVD within a narrow selenium range of 55-145 mu g/l. Our meta-analyses of RCTs showed that oral selenium supplements (median dose: 200 mu g/day) for 2 weeks to 144 months significantly raised the blood selenium concentrations by 56.4 mu g/l (95% confidence interval (CI): 40.9, 72.0 mu g/l), whereas oral selenium supplements (median: 100 mu g/day) for 6 to 114 months caused no effect on CVD (RR = 0.91; 95% CI: 0.74, 1.10). CONCLUSIONS: Our meta-analysis in prospective studies demonstrated a significant inverse association between selenium status and CVD risk within a narrow selenium range and a null effect of selenium supplementation on CVD was observed in RCTs. These findings indicate the importance of considering selenium status, dose and safety in health assessment and future study design.