Chahardoli R, Saboor-Yaraghi AA, Amouzegar A, Khalili D, Vakili AZ, Azizi F. Can supplementation with vitamin D modify thyroid autoantibodies (anti-TPO Ab, anti-Tg Ab) and thyroid profile (T3, T4, TSH) in Hashimoto’s thyroiditis? A double blind, randomized clinical trial. Horm Metab Res. 2019;51(5):296-301.
Randomized, double-blind, placebo-controlled clinical trial.
The study included 42 women aged 18 to 48 years with Hashimoto’s thyroiditis. All participants were treated with levothyroxine for hypothyroidism. Exclusion criteria included diseases of the immune system, liver function abnormalities, malnutrition, body mass index (BMI) <18 or >40, and other autoimmune diseases including type 1 diabetes, inflammatory bowel disease, and multiple sclerosis. Women who had used vitamin D, vitamin A, or omega-3 fatty acid supplements in the past 6 months were also excluded from the study.
Study Parameters Assessed
Participants were randomly divided into 2 groups. One group received oral 50,000 IU vitamin D pearls per week for 3 months. The other group received a placebo pearl made of edible paraffin oil.
At the beginning and end of the study, the researchers measured serum levels of TSH (thyroid-stimulating hormone), T4 (levorotatory thyroxine), T3 (triiodothyronine), 25-hydroxy vitamin D [25(OH)D], calcium, antithyroglobulin antibodies (anti-Tg Ab), and antithyroperoxidase antibodies (anti-TPO Ab). They also assessed at the beginning and end of the study sun exposure (in hours/day) and dietary intake of vitamin D (via dietary record).
Primary Outcome Measures
The primary outcome measures were any changes observed in the blood tests noted above.
After 3 months of supplementation, the vitamin D group had increased serum levels of vitamin D and calcium. There was significant reduction of anti-Tg Ab and TSH over the course of the study. There were no significant changes in anti-TPO Ab levels in the vitamin D group compared to placebo. No significant changes in T3 or T4 levels occurred in either group.
This is the latest of several studies that have shown vitamin D may have an impact on Hashimoto’s thyroiditis.1,2 In addition to the well-known effects of vitamin D on calcium metabolism, vitamin D plays an integral role in regulation of the immune system.2 This study further elucidates its potential for modifying the course of autoimmunity, specifically as it relates to the thyroid.3
Vitamin D receptors are found in lymphocytes, macrophages, and antigen-presenting cells.4 Also, 1-alpha hydroxylase, which is found in antigen-presenting cells, is necessary to convert vitamin D to its active form. Vitamin D also downregulates production of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) as well as decreasing T cell proliferation. Nettore et al note that innate immunity is enhanced and the acquired immune response (such as found in Hashimoto’s thyroiditis) is suppressed in the presence of vitamin D.4
Regardless of the specific cause and effect, the literature is generally associating a decreased autoimmune response with higher levels of vitamin D.
The antibodies found in autoimmune thyroid disease include TPO antibodies and Tg antibodies. TPO is an enzyme that facilitates the synthesis of T4 and T3. Anti-TPO Ab increase production of TNF-α and interferon gamma (IFN-γ). As mentioned above, vitamin D has been shown to inhibit these inflammatory cytokines.
Tg is a glycoprotein present in the thyroid, where thyroid hormones are synthesized. An increase in anti-Tg Ab is associated with an upregulated Th1 and Th2 response. Again, vitamin D suppresses these responses. In this study the effect of vitamin D was more pronounced on anti-Tg Ab than on anti-TPO Ab. Other studies have found a greater impact on anti-TPO Ab,5,6 and another study theorizes that elevated thyroid antibodies cause a decrease in systemic vitamin D.7 Regardless of the specific cause and effect, the literature is generally associating a decreased autoimmune response with higher levels of vitamin D.
It is important to remember that vitamin D is not the only nutrient that plays a role in maintaining and restoring thyroid health. In addition to the obvious substrates for thyroid hormone production (iodine and tyrosine), selenium assists in decreasing antibody titers in Hashimoto’s thyroiditis.8 In keeping with this, the combination of selenomethionine along with vitamin D therapy increased the overall efficacy of therapy.6
With this in mind, when we look at the role of vitamin D in treatment of Hashimoto’s thyroid disease, it is useful to remember that its mechanism likely lies in modifying immune response. In the study reviewed here, there was some change in TSH and thyroid hormone production, but the main benefit was seen in decreasing antibodies. Vitamin D is just one piece of a treatment protocol that addresses the whole person. Strategizing therapies to decrease initiation of the autoimmune response, improve production of T4 and T3, and optimize conversion of T4 to T3 is necessary. Also, addressing stressors, other endocrine imbalances, metabolism, environmental exposures, etc. is a crucial part of a holistic approach to autoimmune thyroid disease.
- Ibrahim NAK, Abbas ZN, mohammad WJ. Association among vitamin D deficiency with some inflammatory marker in Iraqi patients with autoimmune thyroiditis. Indian J Forensic Med Toxicol. 2020;14(1):655-660.
- Villa A, Corsello A, Cintoni M, et al. Effect of vitamin D supplementation on TSH levels in euthyroid subjects with autoimmune thyroiditis. Endocrine. 2020. Online ahead of print. doi: 10.1007/s12020-020-02274-9.
- Kim D. The role of vitamin D in thyroid diseases. Int J Mol Sci. 2017;18(9):1949.
- Nettore IC, Albano L, Ungaro P, et al. Sunshine vitamin and thyroid. Rev Endocr Metab Disord. 2017;18(3):347-354.
- Krysiak R, Szkróbka W, Okopień B.The effect of vitamin D on thyroid autoimmunity in levothyroxine-treated women with Hashimoto's thyroiditis and normal vitamin D status. Exp Clin Endocrinol Diabetes. 2017;125(4):229-233.
- Krysiak R, Kowalcze K, Okopień B. Selenomethionine potentiates the impact of vitamin D on thyroid autoimmunity in euthyroid women with Hashimoto's thyroiditis and low vitamin D status. Pharmacol Rep. 2019;71(2):367-373.
- Botelho IMB, Neto AM, Silva CA, Tambascia MA, Alegre SM, Zantut-Wittmann DE. Vitamin D in Hashimoto's thyroiditis and its relationship with thyroid function and inflammatory status. Endocr J. 2018;65(10):1029-1037.
- Rayman MP. Multiple nutritional factors and thyroid disease, with particular reference to autoimmune thyroid disease.Proc Nutr Soc. 2019;78(1):34-44.