Does vitamin D improve the serum level of anti-TPO and anti-TG in Autoimmune thyroid diseases? A systematic review and meta-analysis
AbstractPurpose: Accumulating evidence suggests vitamin D play a role in autoimmune diseases. However, at this time the finding on its role in autoimmune and thyroid disease is not conclusive. Then, we aimed to review and update data on the effectiveness of vitamin D on thyroid auto antibodies, anti-TPO and anti-TG in adults.Methods: Scopus and PubMed search engines were used up to February 2018 for clinical trials without any restriction in time and language. The outcome parameters were thyroid auto antibodies, anti-TPO and anti-TG. We included studies which reported aim parameters. Results were summarized as mean differences (MD) with 95% confidence intervals (CI). Effect sizes were pooled using random-effects models (the DerSimonian-Laird estimator).Results: Eight trials involving 526 subjects were included in this meta-analysis. Vitamin D supplementation did not significantly changed the serum level of anti-TPO (MD: -46.901 IU/mL, 95% CI: -111.841, 18.039, p=0.157) and anti-TG (MD: -0.903 IU/mL, 95% CI: -2.208, 0.401, p = 0.175) with high heterogeneity (I2= 77.1%, p= 0.000, I2= 26.5%, p= 0.253). Anti-TPO reduction was considerable in mixed-sex and low quality trials, doses of ≥ 1000 IU, periods of ≥ 2 months , AITD patients and in subjects with lower initial serum levels of vitamin D and higher initial serum level of anti-TPO (p <0.0001).Conclusions: Vitamin D supplementation did not improve the serum levels of anti-TPO and anti-TG. The effects of vitamin D supplementing on AITD should be further investigated by conducting larger sample size and well-defined trials of long enough duration.
Jacobson, D.L., et al (1997) Epidemiology and estimated population burden of selected autoimmune diseases in the United States. Clin Immunol Immunopathol. 84(3): 223-43.
Antonelli, A., et al (2015) Autoimmune thyroid disorders. Autoimmun Rev. 14(2): 174-80.
Caturegli, P., A. De Remigis, and N.R. Rose (2014) Hashimoto thyroiditis: clinical and diagnostic criteria. Autoimmun Rev. 13(4-5): 391-7.
Iddah, M.A. and B.N. Macharia (2013) Autoimmune thyroid disorders. ISRN Endocrinol. 2013: 509764.
Dayan, C.M. and G.H. Daniels (1996) Chronic autoimmune thyroiditis. N Engl J Med. 335(2): 99-107.
Pyzik, A., et al (2015) Immune Disorders in Hashimoto’s Thyroiditis: What Do We Know So Far? J Immunol Res. 2015: 8.
Verstuyf, A., et al (2010) Vitamin D: a pleiotropic hormone. Kidney Int. 78(2): 140-5.
Abou-Raya, A., S. Abou-Raya, and M. Helmii (2013) The effect of vitamin D supplementation on inflammatory and hemostatic markers and disease activity in patients with systemic lupus erythematosus: a randomized placebo-controlled trial. J Rheumatol. 40(3): 265-72.
Ananthakrishnan, A.N., et al (2014) Higher plasma 25(OH)D is associated with reduced risk of Clostridium difficile infection in patients with inflammatory bowel diseases. Aliment pharmacol therap. 39(10): 1136-1142.
Arnson, Y., H. Amital, and Y. Shoenfeld (2007) Vitamin D and autoimmunity: new aetiological and therapeutic considerations. Ann Rheum Dis. 66(9): 1137-42.
Deluca, H.F. and M.T. Cantorna (2001) Vitamin D: its role and uses in immunology. Faseb j. 15(14): 2579-85.
Grishkan, I.V., et al (2013) 1,25-Dihydroxyvitamin D3 selectively and reversibly impairs T helper-cell CNS localization. Proc Natl Acad Sci U S A. 110(52): 21101-6.
Lemire, J.M., et al (1984) 1 alpha,25-dihydroxyvitamin D3 suppresses proliferation and immunoglobulin production by normal human peripheral blood mononuclear cells. J Clin Invest. 74(2): 657-661.
Skaaby, T., et al (2015) Prospective population-based study of the association between vitamin D status and incidence of autoimmune disease. Endocrine. 50(1): 231-8.
Choi, Y.M., et al (2014) Low levels of serum vitamin D3 are associated with autoimmune thyroid disease in pre-menopausal women. Thyroid. 24(4): 655-661.
Ma, J., et al (2015) Lower serum 25-hydroxy Vitamin D level is associated with 3 types of autoimmune thyroid diseases. Medicine (United States). 94(39): . e1639.
Yasmeh, J., et al (2016) Hashimoto thyroiditis not associated with vitamin D defficiency. Endocr Pract. 22(7): 809-13.
Effraimidis, G., et al (2012) Vitamin D deficiency is not associated with early stages of thyroid autoimmunity. Eur J Endocrinol. 167(1): 43-8.
Vondra, K., et al (2017) Vitamin D supplementation changed relationships, not levels of metabolic-hormonal parameters in autoimmune thyroiditis. Physiol Res. 66(Supplementum 3): S409-s417.
Krysiak, R., B. Kowalska, and B. Okopien (2015) Serum 25-Hydroxyvitamin D and Parathyroid Hormone Levels in Non-Lactating Women with Post-Partum Thyroiditis: The Effect of L-Thyroxine Treatment. Basic Clin Pharmacol Toxicol. 116(6): 503-7.
Krysiak, R., K. Kowalcze, and B. Okopien (2016) The effect of vitamin D on thyroid autoimmunity in non-lactating women with postpartum thyroiditis. Eur J Clin Nutr. 70(5): 637-9.
Krysiak, R., W. Szkrobka, and B (2017) Okopien, 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. 125(4): 229-233.
Simsek, Y., et al (2016) Effects of Vitamin D treatment on thyroid autoimmunity. Journal of Research in Medical Sciences : The Official Journal of Isfahan University of Medical Sciences . 21: 85.
Moher, D., et al (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 6(7): e1000097.
Richardson, W.S., et al (1995) The well-built clinical question: a key to evidence-based decisions. ACP J Club. 123(3): A12-3.
Jadad, A.R., et al (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 17(1): 1-12.
Higgins JP1, T.S (2002) Quantifying heterogeneity in a meta-analysis. Stat Med,.
Anaraki, P.V., et al (2017) Effects of Vitamin D deficiency treatment on metabolic markers in Hashimoto thyroiditis patients . J Res Med Sci. 22: p. 5
Knutsen, K.V., et al (2017) Effect of Vitamin D on Thyroid Autoimmunity: A Randomized, Double-Blind, Controlled Trial Among Ethnic Minorities. Journal of the Endocrine Society 1(5): 470-479.
Chaudhary, S., et al (2016) Vitamin D supplementation reduces thyroid peroxidase antibody levels in patients with autoimmune thyroid disease: An open-labeled randomized controlled trial. Indian J Endocrinol Metab. 20(3): 391-8.
Mazokopakis, E.E., et al (2015) Is Vitamin D related to pathogenesis and treatment of Hashimoto's thyroiditis? Hell J Nucl Med. 18(3): 222-227.
Vahabi Anaraki, P., et al (2017) Effect of Vitamin D deficiency treatment on thyroid function and autoimmunity markers in Hashimoto's thyroiditis: A double-blind randomized placebo-controlled clinical trial. J Res Med Sci. 22: 103.
Mazokopakis, E.E., et al (2015) Is vitamin D related to pathogenesis and treatment of Hashimoto's thyroiditis? Hell J Nucl Med. 18(3): 222-7.
Simsek, Y., et al (2016) Effects of Vitamin D treatment on thyroid autoimmunity. J Res Med Sci. 21: 85.
Chaudhary, S., et al (2016) Vitamin D supplementation reduces thyroid peroxidase antibody levels in patients with autoimmune thyroid disease: An open-labeled randomized controlled trial. Indian J Endocrinol Metab. 20(3): 391-398.
Goswami, R., et al (2009) Prevalence of vitamin D deficiency and its relationship with thyroid autoimmunity in Asian Indians: a community-based survey. Br J Nutr. 102(3): 382-6.
Antico, A., et al (2012) Can supplementation with vitamin D reduce the risk or modify the course of autoimmune diseases? A systematic review of the literature. Autoimmun Rev. 12(2): 127-36.
Bozkurt, N.C., et al (2013) The association between severity of vitamin D deficiency and Hashimoto's thyroiditis. Endocr Pract. 19(3): 479-484.
Mathieu, C., et al (1992) 1,25-Dihydroxyvitamin D3 prevents insulitis in NOD mice. Diabetes. 41(11): 1491-5.
Chen, W., H. Lin, and M. Wang (2002) Immune intervention effects on the induction of experimental autoimmune thyroiditis. J Huazhong Univ Sci Technolog Med Sci. 22(4): 343-5, 354.
Misharin, A., et al (2009) Vitamin D deficiency modulates Graves' hyperthyroidism induced in BALB/c mice by thyrotropin receptor immunization. Endocrinology. 150(2): 1051-60.
Wang, J., et al (2015) Meta-analysis of the association between vitamin D and autoimmune thyroid disease. Nutrients. 7(4): 2485-98.
Maciejewski, A., et al (2015) Assessment of Vitamin D Level in Autoimmune Thyroiditis Patients and a Control Group in the Polish Population. Adv Clin Exp Med. 24(5): 801-6.
Mansournia, N., et al (2014) The association between serum 25OHD levels and hypothyroid Hashimoto's thyroiditis. J Endocrinol Invest. 37(5): 473-6.
Evliyaoglu, O., et al (2015) Vitamin D Deficiency and Hashimoto's Thyroiditis in Children and Adolescents: a Critical Vitamin D Level for This Association? J Clin Res Pediatr Endocrinol. 7(2): 128-33.
Muscogiuri, G., et al (2016) 25 hydroxyvitamin D deficiency and its relationship to autoimmune thyroid disease in the elderly. IInt J Environ Res Public Health,. 13(9).
Metwalley, K.A., et al (2016) Vitamin D status in children and adolescents with autoimmune thyroiditis. J Endocrinol Invest. 39(7): 793-7.
Kim, D (2016) Low vitamin d status is associated with hypothyroid hashimoto’s thyroiditis. Hormones. 15(3): 385-393.
Tamer, G., et al (2011) Relative vitamin D insufficiency in Hashimoto's thyroiditis. Thyroid. 21(8): 891-6.
Çamurdan, O.M., et al (2012) Vitamin D status in children with Hashimoto thyroiditis. J Pediatr Endocrinol Metab. 25(5-6): 467-470.
Unal, A.D., et al (2014) Vitamin D deficiency is related to thyroid antibodies in autoimmune thyroiditis. Cent Eur J Immunol. 39(4): 493-497.
Arslan, M.S., et al (2015) Isolated vitamin D deficiency is not associated with nonthyroidal illness syndrome, but with thyroid autoimmunity. ScientificWorldJournal. 239815.
Shin, D.Y., et al (2014) Low serum vitamin D is associated with anti-thyroid peroxidase antibody in autoimmune thyroiditis. Yonsei Medical Journal. 55(2): 476-481.
Wortsman, J., et al (2000) Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr. 72(3): 690-3.
Cheng, S., et al (2010) Adiposity, cardiometabolic risk, and vitamin D status: the Framingham Heart Study. Diabetes. 59(1): 242-8.
Liel, Y., et al. (1988) Low circulating vitamin D in obesity. Calcif Tissue Int. 43(4): 199-201.
Blaak, E (2001) Gender differences in fat metabolism. Curr Opin Clin Nutr Metab Care. 4(6): 499-502.
Kojecky, V (2016) A. Adamikova, and P. Klimek, Vitamin D supplementation in inflammatory bowel disease: the role of dosage and patient compliance. Bratisl Lek Listy. 117(3):148-51.
Mahon, B.D., et al (2003) Cytokine profile in patients with multiple sclerosis following vitamin D supplementation. J Neuroimmunol. 134(1-2): 128-32.
Burton, J.M., et al (2010) A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis(e–Pub ahead of print)(LOE Classification). Neurology. 74(23): 1852-1859.
Aranow, C., et al (2015) Randomized, Double-Blind, Placebo-Controlled Trial of the Effect of Vitamin D3 on the Interferon Signature in Patients With Systemic Lupus Erythematosus. Arthritis Rheumatol. 67(7): 1848-57.
Petri, M., et al (2013) Vitamin D in systemic lupus erythematosus: modest association with disease activity and the urine protein-to-creatinine ratio. Arthritis Rheum. 65(7): 1865-71.
Andreoli, L., et al (2015) A 24-month prospective study on the efficacy and safety of two different monthly regimens of vitamin D supplementation in pre-menopausal women with systemic lupus erythematosus. Lupus. 24(4-5): 499-506.