Effects of Selenium Administration on Blood Lipids: A Systematic Review and Dose–Response Meta-Analysis of Experimental Human Studies

Context: Overexposure to the essential trace element selenium has been associated with adverse metabolic and cardiovascular outcomes, hypertension, and diabetes. However, dose–response meta-analyses analyzing the effects of selenium administration on the lipid profile in experimental human studies are lacking. Objective: Through a restricted cubic spline regression meta-analysis, the dose–response relation between the dose of selenium administered or blood selenium concentrations at the end of the trials and changes over time in blood lipids, ie, total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, and triglycerides was assessed. Data Sources: Searches were performed on PubMed, Web of Science, Embase, and the Cochrane Library from inception up to January 11, 2025 to identify randomized controlled trials (RCTs) investigating the impact of selenium supplementation on blood lipid profiles among adults. Data Extraction: A total of 27 eligible RCTs that enrolled healthy individuals, pregnant individuals, and participants with specific health conditions were identified and the relevant data was extracted. Data Analysis: Dose–response analysis indicated that selenium administration at and above 200 µg/day decreased HDL and LDL cholesterol and increased triglyceride levels. Blood selenium concentrations at the end of the trial above approximately 150 µg/L were positively associated with triglyceride and LDL cholesterol concentrations, and inversely associated with HDL cholesterol. Inorganic selenium supplementation showed stronger associations than organic selenium. At the lowest levels of baseline intake, selenium supplementation appeared instead to have beneficial effects on the lipid profile, with an overall indication of U-shaped curves, apart from HDL-cholesterol. The adverse effects of selenium were stronger in studies involving healthy participants as compared with unhealthy participants and pregnant females, in those having a longer duration of the intervention, particularly more than 3 months, and in European populations at selenium intake levels of above 300 µg/day. Conclusions: In this dose–response meta-analysis of experimental human studies, an adverse effect of selenium administration on blood lipids at levels around or above the current upper level of intake was observed.