Selenium Supplementation Significantly Reduces Thyroid Autoantibody Levels in Patients with Chronic Autoimmune Thyroiditis: A Systematic Review and Meta-Analysis

Background: Selenium supplementation may decrease circulating thyroid autoantibodies in patients with chronic autoimmune thyroiditis (AIT), but the available trials are heterogenous. This study expands and critically reappraises the knowledge on this topic. Methods: A literature search identified 3366 records. Controlled trials in adults (18 years of age) with AIT, comparing selenium with or without levothyroxine (LT4), versus placebo and/or LT4, were eligible. Assessed outcomes were serum thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) autoantibody levels, and immunomodulatory effects. After screening and full-text assessment, 16 controlled trials were included in the systematic review. Random-effects meta-analyses in weighted mean difference (WMD) were performed for 3, 6, and 12 months of supplementation in two different populations: one receiving LT4 therapy and one newly diagnosed and LT4-untreated. Heterogeneity was estimated using I-2, and quality of evidence was assessed per outcome, using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines. Results: In LT4-treated populations, the selenium group had significantly lower TPOAb levels after three months (seven studies: WMD=-271 [confidence interval (CI) -366 to -175]; p<0.0001; I-2=45.4%), which was consistent at six months (three studies) and 12 months (one study). TgAb decreased at 12 months, but not at three or six months. In LT4-untreated populations, the selenium group showed a decrease in TPOAb levels after three months (three studies: WMD=-512 [CI -626 to -398]; p<0.0001, I-2=0.0%), but not after 6 or 12 months. TgAb decreased at 3 months, but not at 6 or 12 months. Quality of evidence was generally assessed as low. Study participants receiving selenium had a significantly higher risk than controls of reporting adverse effects (p=0.036). Conclusions: Selenium supplementation reduced serum TPOAb levels after 3, 6, and 12 months in an LT4-treated AIT population, and after three months in an untreated AIT population. Whether these effects correlate with clinically relevant measures remains to be demonstrated.