Effect of high-dose vitamin D supplementation on autoimmunity and thyroid function in women with Hashimoto’s thyroiditis: a randomized crossover clinical trial

Background: Vitamin D exerts immunomodulatory effects that may influence thyroid autoimmunity. In Hashimoto’s thyroiditis (HT), clinical evidence regarding vitamin D supplementation remains limited and heterogeneous. Objective: To evaluate the effect of two cholecalciferol doses aimed at achieving different serum 25(OH)D concentrations (Methods: A randomized, double-blind, crossover clinical trial with an active comparator was conducted. Thirty-four women aged 18 to 45 years with HT, TPOAb ≥35 IU/mL, and serum 25(OH)D Results: No significant differences were observed between treatments in TPOAb or other thyroid parameters (all p > 0.05). In exploratory analyses by achieved serum 25(OH)D concentration, levels ≥40 ng/mL were associated with lower parathyroid hormone levels (ratio, 0.74; 95% CI, 0.62–0.88; p = 0.001) and improved psychological well-being on the ThyPRO-39 (difference, −6.81; 95% CI, −13.19 to −0.43; p = 0.037). No serious adverse events occurred. Conclusion: In women with HT and vitamin D deficiency, high-dose cholecalciferol did not demonstrate a statistically significant effect on thyroid autoimmunity or thyroid function compared with low-dose supplementation over 12 weeks. In exploratory analyses, higher achieved serum 25(OH)D concentrations were associated with a small improvement in psychological well-being.