Endocrinology · Medical Literature
Effect of vitamin D supplementation on thyroid hormones in hypothyroid females of child-bearing age: a systematic review.
Abstract
To assess the impact of vitamin D supplementation on thyroid function and autoimmunity in hypothyroid females of child-bearing age. The systematic review was conducted from October 2024 to May 2025, and comprised search on PubMed, Cochrane Library, Google Scholar and the International Clinical Trials Registry Platform databases using predefined key words and medical subject heading terms, with no date restrictions, up to May 2025. The studies included were randomised controlled and clinical trials in hypothyroid females receiving vitamin D supplementation, and reporting thyroid-stimulating hormone and anti-thyroid peroxidase antibody values. Three reviewers independently screened records, extracted data, and assessed bias using the Cochrane Risk of Bias tool. Of the 384 identified records, 11(2.86%) were analysed in detail. Dosages of vitamin D administered ranged from 800 IU/day to 60,000 IU/week, over 2-24 weeks. Of the total, 9(81.81%) studies reported significant thyroid-stimulating hormone reduction, particularly with ≥50,000 IU/week dose and baseline deficiency correction, whereas anti-thyroid peroxidase antibodies declined in eight autoimmune hypothyroidism studies with three documented more than 50% reduction from baseline. Vitamin D supplementation, especially at higher doses and longer durations, could lower thyroid stimulating hormone and thyroid autoantibodies in hypothyroid females of reproductive age. CRD42023469980.
Clinical relevance
In hypothyroid females of child-bearing age, does vitamin D supplementation significantly reduce thyroid-stimulating hormone (TSH) and anti-thyroid peroxidase (anti-TPO) antibody levels compared to baseline or control? __SNAPSHOT__ {"studyDesign":"Systematic review of randomized controlled trials and clinical trials","setting":"Multicenter/multinational; databases searched: PubMed, Cochrane Library, Google Scholar, and the International Clinical Trials Registry Platform; search conducted October 2024 – May 2025 with no date restrictions","sampleSize":"11 studies included from 384 identified records (2.86% inclusion rate); aggregate participant n not reported in the abstract","population":"Hypothyroid females of child-bearing age receiving vitamin D supplementation and reporting TSH and anti-TPO antibody values; subgroup with autoimmune hypothyroidism analyzed separately for anti-TPO outcomes","intervention":"Vitamin D supplementation; dosages ranging from 800 IU/day to 60,000 IU/week, administered over 2–24 weeks","comparator":"Not explicitly reported in the abstract; individual included trials were described as randomized controlled and clinical trials, implying placebo or no-supplementation comparators in at least some studies","primaryOutcome":"TSH reduction and anti-TPO antibody decline","followUp":"2 to 24 weeks across included studies","fundingSource":"Not reported"}
Key findings
Of 11 included studies, 9 (81.8%) reported a statistically significant reduction in TSH, with the effect most pronounced at doses ≥50,000 IU/week and in participants with documented baseline vitamin D deficiency who achieved correction of that deficiency. Anti-TPO antibodies declined in 8 studies that specifically enrolled patients with autoimmune hypothyroidism. Absolute and relative effect sizes (e.g., mean TSH reduction in mIU/L, percent change in anti-TPO), confidence intervals, p-values, and heterogeneity statistics (I²) are not reported in the abstract. NNT/NNH cannot be calculated from available data. No specific adverse events were reported in the abstract. Risk of bias was assessed using the Cochrane Risk of Bias tool; results of that assessment are not detailed in the abstract.
Practice implications
This systematic review suggests that vitamin D supplementation may reduce TSH and anti-TPO antibody levels in hypothyroid females of child-bearing age, particularly when baseline vitamin D deficiency is corrected and higher weekly doses (≥50,000 IU/week) are used. However, several key uncertainties preclude definitive clinical conclusions: (1) Only the abstract was available for review, and full methodology, risk-of-bias results, effect sizes, heterogeneity statistics, and pooled estimates are not accessible; (2) the inclusion of only 11 studies from 384 records, with heterogeneous dosing regimens (800 IU/day to 60,000 IU/week) and follow-up durations (2–24 weeks), limits the ability to identify an optimal dose or treatment duration; (3) the review is restricted to females of child-bearing age, limiting generalizability to males, postmenopausal women, and pediatric populations; (4) whether TSH and anti-TPO reductions translate into clinically meaningful outcomes (e.g., reduced levothyroxine requirements, improved quality of life, pregnancy outcomes, or reduced progression to overt hypothyroidism) is not established by this review; (5) the absence of reported aggregate participant numbers precludes assessment of statistical power; and (6) the distinction between autoimmune hypothyroidism (Hashimoto's thyroiditis) and non-autoimmune etiologies is partially addressed but not fully resolved across all 11 studies. These findings are hypothesis-generating and should not be used to alter current management protocols without corroborating evidence from adequately powered, pre-registered RCTs with clinically meaningful primary endpoints. __LIMITATIONS__ Only the abstract was available; full methodology, risk-of-bias summary, pooled effect sizes, and heterogeneity data cannot be evaluated.,Small number of included studies (n=11) from a large initial pool (384 records); high exclusion rate raises the possibility of selection bias.,Highly heterogeneous vitamin D dosing (800 IU/day to 60,000 IU/week) and follow-up duration (2–24 weeks) make dose-response conclusions unreliable and preclude robust pooled estimates.,Total aggregate participant number across included trials is not reported, preventing assessment of statistical power.,TSH and anti-TPO antibody are surrogate endpoints; no patient-important outcomes (e.g., levothyroxine dose reduction, pregnancy outcomes, quality of life, progression to overt hypothyroidism) are reported.,Restriction to females of child-bearing age limits generalizability; males, older women, and adolescents are excluded.,Blinding status, allocation concealment, and comparator arms of individual included trials are not described in the abstract.,The Cochrane Risk of Bias tool was applied, but results are not detailed in the abstract, preventing assessment of overall study quality.,Funding sources for neither the systematic review nor the included primary studies are disclosed, precluding assessment of sponsorship bias.,The 2-week minimum follow-up in some included trials is unlikely to be sufficient to detect sustained thyroid hormonal effects. __BOTTOM_LINE_CATEGORY__ promising_but_preliminary __BOTTOM_LINE__ This systematic review of 11 trials suggests that vitamin D supplementation—particularly at doses ≥50,000 IU/week with correction of baseline deficiency—may reduce TSH and anti-TPO antibody levels in hypothyroid females of child-bearing age, but effect sizes, pooled estimates, and confidence intervals are not reported in the available abstract. Given the absence of patient-important outcome data, marked heterogeneity in dosing protocols, and the surrogate-endpoint focus, these findings are preliminary and insufficient to change clinical practice. Clinicians should screen for and treat vitamin D deficiency as indicated by established guidelines, but should not yet use vitamin D supplementation as a therapeutic strategy for hypothyroidism outside of a formal clinical trial context.