Selenium and immune function: a systematic review and meta-analysis of experimental human studies

Background Selenium is an essential trace element with both beneficial and detrimental effects on health depending on dose and chemical form. Currently, there is debate about recommendations for selenium supplementation as a public health measure to improve immune function and reduce infectious disease susceptibility. Objectives We performed a systematic review and meta-analysis of experimental studies assessing the effect of selenium supplementation on immunity-related outcomes in healthy people. Methods We undertook a search of published and unpublished studies in literature databases PubMed/MEDLINE, Embase and Clinicaltrials.gov up to October 17, 2022, and performed a meta-analysis comparing the effects on immunity-related outcomes between supplemented versus control arms. Whenever possible we assessed the nonlinear relation using a dose-response approach. Results Nine trials were included, five in North America, and four in Europe, with duration between 8-48 weeks and supplementation of both inorganic and organic selenium forms. Selenium supplementation did not substantially affect immunoglobulin or white blood cell levels, and the dose-response meta-analysis indicated that an increase in plasma selenium concentrations above 100 μg/L did not further increase IgA levels nor T-cells. An inverted U-shaped relation emerged for Natural killer (NK) cell count, with lower number of these cells both below and above 120 μg/L. The only beneficial effect of selenium supplementation was increased activity for NKlysis, but the available data did not permit dose-response analysis. Cytokine levels were substantially unaffected by selenium supplementation. Conclusions Although some of the data suggested beneficial effects of selenium supplementation on immune function, the overall picture appears to be inconsistent and heterogenous due to differences in trial duration and interventions, plus evidence of null and even detrimental effects. Overall, the evidence that we extracted from the literature in this systematic review does not support the need to supplement selenium beyond the recommended dietary intake to obtain beneficial effects on immune function. Keywords seleniumimmune functioninfectious diseaseexperimental studiessystematic reviewdose-response meta-analysis