Selenium Supplementation Reduces Thyroid Antibodies in Hashimoto Thyroiditis: Systematic Review and Meta-Analysis of 21 Randomized Controlled Trials
View StudyPlain-Language Summary
A systematic review and meta-analysis of 21 randomized controlled trials involving 1,610 patients with Hashimoto thyroiditis found that selenium supplementation significantly reduced levels of the key thyroid autoantibody TPOAb at both 3 and 6 months, with the organic form selenomethionine showing the strongest effects. Patients who received selenium also had significantly improved well-being and mood compared to those taking placebo, and TSH levels declined meaningfully after six months of supplementation. The findings add to growing evidence that selenium, an essential trace element highly concentrated in thyroid tissue, plays a meaningful role in managing the autoimmune inflammation that drives Hashimoto disease.
Abstract
Hashimoto thyroiditis (HT) is the most common autoimmune endocrine disorder and the leading cause of hypothyroidism in iodine-sufficient regions. It is characterized by elevated levels of antithyroid peroxidase antibody (TPOAb) and antithyroglobulin antibody (TgAb), lymphocytic infiltration of thyroid tissue, and progressive destruction of thyroid follicular cells. Selenium deficiency has been proposed as a contributing environmental factor: the thyroid gland contains the highest selenium concentration per unit of tissue in the body, and selenoproteins including glutathione peroxidases protect thyroid cells from oxidative stress generated during hormone synthesis. Prior meta-analyses have shown inconsistent results across different selenium formulations and patient populations, and no prior analysis had systematically compared selenomethionine, sodium selenite, and selenium-yeast side by side.
This PRISMA-based systematic review searched eight databases for randomized controlled trials of selenium supplementation in adults with Hashimoto thyroiditis published from inception through April 2022. Twenty-one studies enrolling a total of 1,610 subjects were included. Primary outcomes were changes in TPOAb, TgAb, and thyroid-stimulating hormone (TSH); secondary outcomes included free triiodothyronine (FT3), free thyroxine (FT4), patient well-being, and adverse effects. Risk of bias was assessed using Cochrane Handbook criteria. Subgroup analyses stratified findings by selenium formulation: selenomethionine (Seme), sodium selenite (NaSe), and selenium-yeast.
Selenium supplementation produced a statistically significant reduction in serum TPOAb at both 3 months (standardized mean difference [SMD] = -0.46, 95% CI: -0.74 to -0.18, p = 0.001) and 6 months (SMD = -0.80, 95% CI: -1.38 to -0.21, p = 0.008). TgAb declined significantly at 3 months but not at 6 months. TSH levels were significantly lower after 6 months of supplementation (SMD = -0.18, 95% CI: -0.35 to -0.01, p = 0.03). Patients receiving selenium were 2.79 times more likely to report improved well-being or mood versus placebo (RR = 2.79, 95% CI: 1.21 to 6.47, p = 0.02). Subgroup analysis confirmed that selenomethionine at 200 mcg/day was the most effective formulation, producing a significant TPOAb reduction at 3 months (SMD = -0.67, p = 0.01), while sodium selenite and selenium-yeast did not reach significance in subgroup analyses. Adverse effects, primarily gastrointestinal discomfort, were more common in selenium-treated patients but were generally mild. No changes in FT3 or FT4 were detected across the observation period. The authors conclude that selenium supplementation, particularly in selenomethionine form at 200 mcg/day, is a safe adjunctive strategy that reduces TPOAb and TSH while improving subjective well-being in patients with Hashimoto thyroiditis.