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 μg/l and a significant benefit of CVD within a narrow selenium range of 
55-145 μg/l. Our meta-analyses of RCTs showed that oral selenium supplements 
(median dose: 200 μg/day) for 2 weeks to 144 months significantly raised the 
blood selenium concentrations by 56.4 μg/l (95% confidence interval (CI): 40.9, 
72.0 μg/l), whereas oral selenium supplements (median: 100 μg/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.