Regan Licciardello

Background: Hashimoto’s disease is the most common autoimmune condition that impacts the thyroid gland.¹ Pathogenesis of Hashimoto’s involves both B lymphocytes creating autoantibodies against the thyroid gland and T lymphocytes proliferating into Th1 and Th17 proinflammatory cell types.² If left untreated, Hashimoto’s eventually causes thyroid cell apoptosis in disease end stages.² Clinical symptoms of the condition include dry skin, hair loss, constipation, irritability, weight gain, lack of concentration, fatigue and depression.² Hashimoto’s is diagnosed by the presence of anti-thyroid peroxidase antibody biomarker (anti-TPO).² The standard current treatment is Levothyroxine which acts as an artificial T4 (thyroxine) to bypass the body’s lack of ability to produce the thyroid hormone, providing relief of symptoms.² In cases where symptoms are too severe, a partial or total thyroidectomy can be considered. While it is known that nutritional deficiencies in Vitamin D increase an individual’s chance of developing Hashimoto’s disease, research gaps are still present in investigating alternative ways to minimize the autoimmune response in Hashimoto’s disease to address negative symptoms, reduce inflammation and promote well-being for patients.³

Objective: Vitamin D is classified as an immunomodulator and it is hypothesized that supplementation of Vitamin D can minimize inflammation and reduce side-effects in Hashimoto’s patients.³

Search Methods: An online search in the PubMed database was conducted from 2017-2025 using the following keywords: “Hashimotos”, Vitamin D”, “Inflammation” and “Lymphocytes”.

Results: Studies show that Vitamin D works to reduce thyroid tissue damage and thyroid peroxidase antibody levels in mice models induced to have autoimmune thyroiditis, indicating a reduced autoimmune response against the thyroid gland.⁴ Vitamin D also promotes Treg upregulation and differentiation of B lymphocytes into anti-inflammatory B cells while simultaneously inhibiting differentiation of T lymphocytes into pro-inflammatory cells like Th17 and Th1in similar mice models.⁴ Autoimmune thyroiditis mice treated with Vitamin D were further found to have increased Yap protein expression, which is a transcription factor that activates the JAK/STAT pathway indirectly by upregulating STAT5, an anti-inflammatory molecule and downregulating STAT3, a pro-inflammatory molecule.⁵ Moreover, Vitamin D significantly suppressed Th17 cell production in an in vitro experiment indirectly by regulating the NF-κB pathway via translocation of p65.⁶ Lastly, one preliminary clinical trial found that Vitamin D decreases the Th17/Tr1 ratio in women with Hashimoto’s, minimizing inflammatory levels in those patients.⁷

Conclusions: Studies have found that Vitamin D has potential for reducing inflammation in Hashimoto’s patients through three main mechanisms. Vitamin D promotes B and T lymphocyte differentiation into anti-inflammatory forms, while also decreasing levels of thyroid peroxidase antibodies in mice and reducing the Th17/Treg ratio in adult female humans. These results indicate that Vitamin D may reduce the inflammatory response associated with Hashimoto’s disease and may be a valuable asset in treatment. Consideration of Vitamin D supplementation could lead to alternative treatment avenues for Hashimoto’s patients.

Works Cited:

1. Vargas-Uricoechea H. Molecular Mechanisms in Autoimmune Thyroid Disease. Cells. 2023 Mar 16;12(6):918. doi: 10.3390/cells12060918. PMID: 36980259; PMCID: PMC10047067.
2. Wrońska K, Hałasa M, Szczuko M. The Role of the Immune System in the Course of Hashimoto’s Thyroiditis: The Current State of Knowledge. Int J Mol Sci. 2024 Jun 23;25(13):6883. doi: 10.3390/ijms25136883. PMID: 38999993; PMCID: PMC11241408.
3. Zhao R, Zhang W, Ma C, Zhao Y, Xiong R, Wang H, Chen W, Zheng SG. Immunomodulatory Function of Vitamin D and Its Role in Autoimmune Thyroid Disease. Front Immunol. 2021 Feb 19;12:574967. doi: 10.3389/fimmu.2021.574967. PMID: 33679732; PMCID: PMC7933459.
4. Wang CM, Chen YJ, Yang BC, et al. Supplementation with active vitamin D3 ameliorates experimental autoimmune thyroiditis in mice by modulating the differentiation and functionality of intrathyroidal T-cell subsets. Front Immunol. 2025;16:1528707. Published 2025 Jan 30. doi:10.3389/fimmu.2025.1528707
5. Zhang Q, He X, Chen W, Jiu J, Gao C, Gao T. Vitamin D3 attenuates autoimmune thyroiditis by regulating Th17/Treg cell differentiation via YAP/JAK1/STAT1 axis. Immunol Lett. 2024;269:106890. doi:10.1016/j.imlet.2024.106890
6. Sun D, Luo F, Xing JC, Zhang F, Xu JZ, Zhang ZH. 1,25(OH)2 D3 inhibited Th17 cells differentiation via regulating the NF-κB activity and expression of IL-17. Cell Prolif. 2018;51(5):e12461. doi:10.1111/cpr.12461
7. Nodehi M, Ajami A, Izad M, et al. Effects of vitamin D supplements on frequency of CD4+ T-cell subsets in women with Hashimoto’s thyroiditis: a double-blind placebo-controlled study. Eur J Clin Nutr. 2019;73(9):1236-1243. doi:10.1038/s41430-019-0395-z