Selenium Supplementation in Rheumatoid Arthritis: Evidence from Controlled Clinical Trials and Mechanistic Insights

Selenium (Se) is a key micronutrient integrated into selenoproteins such as glutathione peroxidases (GPx), which are responsible for crucial antioxidant and anti-inflammatory mechanisms. Oxidative stress contributes to the immunopathogenesis and chronic joint damage of rheumatoid arthritis (RA), supporting interest in selenium supplementation as an adjunct therapeutic strategy. This review was based on a structured literature search of major biomedical databases and evaluated six controlled clinical trials involving a total of 234 RA patients who received selenium supplementation at daily doses of 200-256 μg for 12-26 weeks. Given the substantial clinical and methodological heterogeneity among trials—including differences in disease stage, selenium formulation, outcome measures, and trial duration—a quantitative meta-analysis was not performed, and a qualitative synthesis was undertaken. Supplementation consistently increased circulating selenium levels and enhanced GPx activity, particularly in erythrocytes. Clinical outcomes were heterogeneous: one study in early RA demonstrated significant improvements in joint symptoms and functional parameters versus placebo, whereas trials in long-standing disease generally showed biochemical benefits without significant differences in pain, joint counts, or inflammatory markers compared with control groups. More recent studies reported favorable within-group reductions in ESR, CRP, and anti-CCP titers, but between-group differences remained non-significant. This pattern highlights a dissociation between biochemical improvement and consistent clinical benefit, particularly in established RA. Selenium supplementation was well tolerated in all trials, with no major adverse events. These findings suggest that selenium may have therapeutic relevance in selected patient subgroups, including those with recent-onset disease or elevated oxidative burden. However, due to heterogeneity and limited sample sizes, conclusions should be interpreted with caution. Larger, rigorously designed clinical trials with standardized disease activity endpoints, stratification by disease stage and baseline selenium status, are needed to clarify selenium’s role within contemporary RA management.