Abstract
In the last few years, more attention has been given to the “non-calcemic” effect of vitamin D. Several observational studies and meta-analyses demonstrated an association between circulating levels of vitamin D and outcome of many common diseases, including endocrine diseases, chronic diseases, cancer progression, and autoimmune diseases. In particular, cells of the immune system (B cells, T cells, and antigen presenting cells), due to the expression of 1α-hydroxylase (CYP27B1), are able to synthesize the active metabolite of vitamin D, which shows immunomodulatory properties. Moreover, the expression of the vitamin D receptor (VDR) in these cells suggests a local action of vitamin D in the immune response. These findings are supported by the correlation between the polymorphisms of the VDR or the CYP27B1 gene and the pathogenesis of several autoimmune diseases. Currently, the optimal plasma 25-hydroxyvitamin D concentration that is necessary to prevent or treat autoimmune diseases is still under debate. However, experimental studies in humans have suggested beneficial effects of vitamin D supplementation in reducing the severity of disease activity. In this review, we summarize the evidence regarding the role of vitamin D in the pathogenesis of autoimmune endocrine diseases, including type 1 diabetes mellitus, Addison’s disease, Hashimoto’s thyroiditis, Graves’ disease and autoimmune polyendocrine syndromes. Furthermore, we discuss the supplementation with vitamin D to prevent or treat autoimmune diseases.
This is a preview of subscription content, access via your institution.

References
Aranow C. Vitamin D, and the immune system. J Investig Med Off Publ Am Fed Clin Res. 2011;59(6):881–6. doi:10.2310/JIM.0b013e31821b8755.
Bikle DD. Vitamin D, metabolism, mechanism of action, and clinical applications. Chem Biol. 2014;21(3):319–29. doi:10.1016/j.chembiol.2013.12.016.
Holick MF. Vitamin D, deficiency. New Engl J Med. 2007;357(3):266–81. doi:10.1056/NEJMra070553.
Battault S, Whiting SJ, Peltier SL, Sadrin S, Gerber G, Maixent JM. Vitamin D metabolism, functions, and needs: from science to health claims. Eur J Nutr. 2013;52(2):429–41. doi:10.1007/s00394-012-0430-5.
Muscogiuri G, Mitri J, Mathieu C, Badenhoop K, Tamer G, Orio F, et al. Mechanisms in endocrinology: vitamin D as a potential contributor in endocrine health and disease. Eur J Endocrinol / Eur Fed Endocr Soc. 2014;171(3):R101–10. doi:10.1530/EJE-14-0158.
Muscogiuri G, Altieri B, Annweiler C, Balercia G, Pal HB, Boucher BJ, et al. Vitamin D and chronic diseases: the current state of the art. Arch Toxicol. 2016. doi:10.1007/s00204-016-1804-x.
Altieri B, Grant WB, Casa SD, Orio F, Pontecorvi A, Colao A, et al. Vitamin D and pancreas: the role of sunshine vitamin in the pathogenesis of diabetes mellitus and pancreatic cancer. Crit Rev Food Sci Nutr. 2016. doi:10.1080/10408398.2015.1136922.
Moukayed M, Grant WB. Molecular link between vitamin D and cancer prevention. Nutrients. 2013;5(10):3993–4021. doi:10.3390/nu5103993.
Bikle D. Nonclassic actions of vitamin D. J Clin Endocrinol Metab. 2009;94(1):26–34. doi:10.1210/jc.2008-1454.
Hewison M, Gacad MA, Lemire J, Adams JS. Vitamin D as a cytokine and hematopoetic factor. Rev Endocr Metab Disord. 2001;2(2):217–27.
van Etten E, Mathieu C. Immunoregulation by 1,25-dihydroxyvitamin D3: basic concepts. J Steroid Biochem Mol Biol. 2005;97(1/2):93–101. doi:10.1016/j.jsbmb.2005.06.002.
Hossein-Nezhad A, Spira A, Holick MF. Influence of vitamin D status and vitamin D3 supplementation on genome wide expression of white blood cells: a randomized double-blind clinical trial. PLoS One. 2013;8(3):e58725. doi:10.1371/journal.pone.0058725.
Hewison M. Vitamin D and the immune system: new perspectives on an old theme. Endocrinol Metab Clin N Am. 2010;39(2):365–79. doi:10.1016/j.ecl.2010.02.010.
Prietl B, Treiber G, Pieber TR, Amrein K. Vitamin D and immune function. Nutrients. 2013;5(7):2502–21. doi:10.3390/nu5072502.
Kearns MD, Alvarez JA, Seidel N, Tangpricha V. Impact of vitamin D on infectious disease. Am J Med Sci. 2015;349(3):245–62. doi:10.1097/MAJ.0000000000000360.
Autier P, Boniol M, Pizot C, Mullie P. Vitamin D status and ill health: a systematic review. Lancet Diabetes Eendocrinol. 2014;2(1):76–89. doi:10.1016/S2213-8587(13)70165-7.
Kamen DL, Tangpricha V. Vitamin D and molecular actions on the immune system: modulation of innate and autoimmunity. J Mol Med (Berlin). 2010;88(5):441–50. doi:10.1007/s00109-010-0590-9.
Rosen Y, Daich J, Soliman I, Brathwaite E, Shoenfeld Y. Vitamin D and autoimmunity. Scand J Rheumatol 2016:1–9 doi:10.3109/03009742.2016.1151072.
Borges MC, Martini LA, Rogero MM. Current perspectives on vitamin D, immune system, and chronic diseases. Nutrition. 2011;27(4):399–404. doi:10.1016/j.nut.2010.07.022.
Grad R. Cod and the consumptive: a brief history of cod-liver oil in the treatment of pulmonary tuberculosis. Pharm Hist. 2004;46(3):106–20.
Griffin MD, Lutz WH, Phan VA, Bachman LA, McKean DJ, Kumar R. Potent inhibition of dendritic cell differentiation and maturation by vitamin D analogs. Biochem Biophys Res Commun. 2000;270(3):701708. doi:10.1006/bbrc.2000.2490.
Bartley J. Vitamin D: emerging roles in infection and immunity. Expert Rev Anti-Infect Ther. 2010;8(12):1359–69. doi:10.1586/eri.10.102.
Kivity S, Agmon-Levin N, Blank M, Shoenfeld Y. Infections and autoimmunity—friends or foes? Trends Immunol. 2009;30(8):409–14. doi:10.1016/j.it.2009.05.005.
Borella E, Nesher G, Israeli E, Shoenfeld Y. Vitamin D: a new anti-infective agent? Ann NY Acad Sci. 2014;1317:76–83. doi:10.1111/nyas.12321.
Yenamandra SP, Lundin A, Arulampalam V, Yurchenko M, Pettersson S, Klein G, et al. Expression profile of nuclear receptors upon Epstein–Barr virus induced B cell transformation. Exp Oncol. 2009;31(2):92–6.
Bizzaro G, Shoenfeld Y. Vitamin D and autoimmune thyroid diseases: facts and unresolved questions. Immunol Res. 2015;61(1/2):46–52. doi:10.1007/s12026-014-8579-z.
Dimeloe S, Nanzer A, Ryanna K, Hawrylowicz C. Regulatory T cells, inflammation, and the allergic response—The role of glucocorticoids and Vitamin D. J S Biochem Mol Biol. 2010;120(2/3):86–95. doi:10.1016/j.jsbmb.2010.02.029.
Figueiredo AS, Schumacher A. The T helper type 17/regulatory T cell paradigm in pregnancy. Immunology. 2016;148(1):13–21. doi:10.1111/imm.12595.
Ullah MI, Koch CA, Tamanna S, Rouf S, Shamsuddin L. Vitamin D deficiency and the risk of preeclampsia and eclampsia in Bangladesh. Hormone Metab Res [Hormon- und Stoffwechselforschung] [Hormones et metabolisme]. 2013;45(9):682–7. doi:10.1055/s-0033-1345199.
Chen S, Sims GP, Chen XX, Gu YY, Chen S, Lipsky PE. Modulatory effects of 1,25-dihydroxyvitamin D3 on human B cell differentiation. J Immunol. 2007;179(3):1634–47.
Zhang J, Li W, Liu J, Wu W, Ouyang H, Zhang Q, et al. Polymorphisms in the vitamin D receptor gene and type 1 diabetes mellitus risk: an update by meta-analysis. Mol Cell Endocrinol. 2012;355(1):135–42. doi:10.1016/j.mce.2012.02.003.
Ban Y, Taniyama M, Yanagawa T, Yamada S, Maruyama T, Kasuga A. Vitamin D receptor initiation codon polymorphism influences genetic susceptibility to type 1 diabetes mellitus in the Japanese population. BMC Med Genet. 2001;2:7.
Kahles H, Morahan G, Todd JA, Badenhoop K. Association analyses of the vitamin D receptor gene in 1654 families with type I diabetes. Genes Immun. 2009;10 Suppl 1:S60–3. doi:10.1038/gene.2009.93.
van Etten E, Verlinden L, Giulietti A, Ramos-Lopez E, Branisteanu DD, Ferreira GB, et al. The vitamin D receptor gene FokI polymorphism: functional impact on the immune system. Eur J Immunol. 2007;37(2):395–405. doi:10.1002/eji.200636043.
Moltchanova EV, Schreier N, Lammi N, Karvonen M. Seasonal variation of diagnosis of type 1 diabetes mellitus in children worldwide. Diabet Med. 2009;26(7):673–8. doi:10.1111/j.1464-5491.2009.02743.x.
Stene LC, Ulriksen J, Magnus P, Joner G. Use of cod liver oil during pregnancy associated with lower risk of type I diabetes in the offspring. Diabetologia. 2000;43(9):1093–8.
Stene LC, Joner G. Use of cod liver oil during the first year of life is associated with lower risk of childhood-onset type 1 diabetes: a large, population-based, case-control study. Am J Clin Nutr. 2003;78(6):1128–34.
Marjamaki L, Niinisto S, Kenward MG, Uusitalo L, Uusitalo U, Ovaskainen ML, et al. Maternal intake of vitamin D during pregnancy and risk of advanced beta cell autoimmunity and type 1 diabetes in offspring. Diabetologia. 2010;53(8):1599–607. doi:10.1007/s00125-010-1734-8.
Zipitis CS, Akobeng AK. Vitamin D supplementation in early childhood and risk of type 1 diabetes: a systematic review and meta-analysis. Arch Dis Child. 2008;93(6):512–7. doi:10.1136/adc.2007.128579.
Wolden-Kirk H, Rondas D, Bugliani M, Korf H, Van Lommel L, Brusgaard K, et al. Discovery of molecular pathways mediating 1,25-dihydroxyvitamin D3 protection against cytokine-induced inflammation and damage of human and male mouse islets of Langerhans. Endocrinology. 2014;155(3):736–47. doi:10.1210/en.2013-1409.
Wolden-Kirk H, Overbergh L, Christesen HT, Brusgaard K, Mathieu C. Vitamin D and diabetes: its importance for beta cell and immune function. Mol Cell Endocrinol. 2011;347(1/2):106–20. doi:10.1016/j.mce.2011.08.016.
Pitocco D, Crino A, Di Stasio E, Manfrini S, Guglielmi C, Spera S, et al. The effects of calcitriol and nicotinamide on residual pancreatic beta-cell function in patients with recent-onset Type 1 diabetes (IMDIAB XI). Diabetes Med. 2006;23(8):920–3. doi:10.1111/j.1464-5491.2006.01921.x.
Papadimitriou DT, Marakaki C, Fretzayas A, Nicolaidou P, Papadimitriou A. Negativation of type 1 diabetes-associated autoantibodies to glutamic acid decarboxylase and insulin in children treated with oral calcitriol. J Diabetes. 2013;5(3):344–8. doi:10.1111/1753-0407.12023.
Li X, Liao L, Yan X, Huang G, Lin J, Lei M, et al. Protective effects of 1-alpha-hydroxyvitamin D3 on residual beta-cell function in patients with adult-onset latent autoimmune diabetes (LADA). Diabetes/Met Res Rev. 2009;25(5):411–6. doi:10.1002/dmrr.977.
Walter M, Kaupper T, Adler K, Foersch J, Bonifacio E, Ziegler AG. No effect of the 1alpha,25-dihydroxyvitamin D3 on beta-cell residual function and insulin requirement in adults with new-onset type 1 diabetes. Diabetes Care. 2010;33(7):1443–8. doi:10.2337/dc09-2297.
Michels AW, Eisenbarth GS. Autoimmune polyendocrine syndrome type 1 (APS-1) as a model for understanding autoimmune polyendocrine syndrome type 2 (APS-2). J Intern Med. 2009;265(5):530–40. doi:10.1111/j.1365-2796.2009.02091.x.
Bratland E, Husebye ES. Cellular immunity and immunopathology in autoimmune Addison’s disease. Mol Cell Endocrinol. 2011;336(1/2):180–90. doi:10.1016/j.mce.2010.12.015.
Pani MA, Seissler J, Usadel KH, Badenhoop K. Vitamin D receptor genotype is associated with Addison’s disease. Eur J Endocrinol / Eur Fed Endocr Soc. 2002;147(5):635–40.
Lopez ER, Zwermann O, Segni M, Meyer G, Reincke M, Seissler J, et al. A promoter polymorphism of the CYP27B1 gene is associated with Addison’s disease, Hashimoto’s thyroiditis, Graves’ disease, and type 1 diabetes mellitus in Germans. Eur J Endocrinol / Eur Fed Endocr Soc. 2004;151(2):193–7.
Fichna M, Zurawek M, Januszkiewicz-Lewandowska D, Gryczynska M, Fichna P, Sowinski J. Association of the CYP27B1 C(-1260)A polymorphism with autoimmune Addison’s disease. Exp Clin Endocrinol Diabetes Off J German Soc Endocrinol German Diabetes Assoc. 2010;118(8):544–9. doi:10.1055/s-0029-1241206.
Jennings CE, Owen CJ, Wilson V, Pearce SH. A haplotype of the CYP27B1 promoter is associated with autoimmune Addison’s disease but not with Graves’ disease in a UK population. J Mol Endocrinol. 2005;34(3):859–63. doi:10.1677/jme.1.01760.
Gittoes NJ. Vitamin D—what is normal according to latest research and how should we deal with it? Clin Med. 2016;16(2):171–4. doi:10.7861/clinmedicine.16-2-171.
Ramagopalan SV, Goldacre R, Disanto G, Giovannoni G, Goldacre MJ. Hospital admissions for vitamin D-related conditions and subsequent immune-mediated disease: record-linkage studies. BMC Med. 2013;11:171. doi:10.1186/1741-7015-11-171.
Bellastella G, Maiorino MI, Petrizzo M, De Bellis A, Capuano A, Esposito K, et al. Vitamin D and autoimmunity: what happens in autoimmune polyendocrine syndromes? J Endocrinol Investig. 2015;38(6):629–33. doi:10.1007/s40618-014-0233-z.
Montoli A, Colussi G, Minetti L. Hypercalcaemia in Addison’s disease: calciotropic hormone profile and bone histology. J Intern Med. 1992;232(6):535–40.
Suliman AM, Freaney R, Smith TP, McBrinn Y, Murray B, McKenna TJ. The impact of different glucocorticoid replacement schedules on bone turnover and insulin sensitivity in patients with adrenal insufficiency. Clin Endocrinol. 2003;59(3):380–7.
Muscogiuri G, Tirabassi G, Bizzaro G, Orio F, Paschou SA, Vryonidou A, et al. Vitamin D and thyroid disease: to D or not to D? Eur J Clin Nutr. 2015;69(3):291–6. doi:10.1038/ejcn.2014.265.
Wang J, Lv S, Chen G, Gao C, He J, Zhong H, et al. Meta-analysis of the association between vitamin D and autoimmune thyroid disease. Nutrients. 2015;7(4):2485–98. doi:10.3390/nu7042485.
Sonmezgoz E, Ozer S, Yilmaz R, Onder Y, Butun I, Bilge S. Hypovitaminosis D in children with Hashimotos thyroiditis. Rev Med Chil. 2016;144(5):611–6. doi:10.4067/S0034-98872016000500009.
Muscogiuri G, Mari D, Prolo S, Fatti LM, Cantone MC, Garagnani P, et al. Hydroxyvitamin D deficiency and its relationship to autoimmune thyroid disease in the elderly. Int J Environ Res Public Health. 2016;13(9). doi:10.3390/ijerph13090850.
Mazokopakis EE, Papadomanolaki MG, Tsekouras KC, Evangelopoulos AD, Kotsiris DA, Tzortzinis AA. Is vitamin D related to pathogenesis and treatment of Hashimoto’s thyroiditis? Hell J Nucl Med. 2015;18(3):222–7.
Maciejewski A, Wojcicka M, Roszak M, Losy J, Lacka K. Assessment of vitamin D level in autoimmune thyroiditis patients and a control group in the Polish population. Adv Clin Exp Med Off Organ Wroclaw Med Univ. 2015;24(5):801–6. doi:10.17219/acem/29183.
Chaudhary S, Dutta D, Kumar M, Saha S, Mondal SA, Kumar A, et al. Vitamin D supplementation reduces thyroid peroxidase antibody levels in patients with autoimmune thyroid disease: an open-labeled randomized controlled trial. Indian J Endocrinol Metab. 2016;20(3):391–8. doi:10.4103/2230-8210.179997.
Effraimidis G, Badenhoop K, Tijssen JG, Wiersinga WM. Vitamin D deficiency is not associated with early stages of thyroid autoimmunity. Eur J Endocrinol / Eur Fed Endocr Soc. 2012;167(1):43–8. doi:10.1530/EJE-12-0048.
Goswami R, Marwaha RK, Gupta N, Tandon N, Sreenivas V, Tomar N, et al. Prevalence of vitamin D deficiency and its relationship with thyroid autoimmunity in Asian Indians: a community-based survey. Br J Nutr. 2009;102(3):382–6. doi:10.1017/S0007114509220824.
Yasmeh J, Farpour F, Rizzo V, Kheradnam S, Sachmechi I. Hashimoto thyroiditis not associated with vitamin D deficiency. Endocr Pract Off J Am Coll Endocrinol Am Assoc Clin Endocrinol. 2016;22(7):809–13. doi:10.4158/EP15934.OR.
Yazici D, Yavuz D, Tarcin O, Sancak S, Deyneli O, Akalin S. Vitamin D receptor gene ApaI, TaqI, FokI, and BsmI polymorphisms in a group of Turkish patients with Hashimoto’s thyroiditis. Minerva Endocrinol. 2013;38(2):195–201.
Inoue N, Watanabe M, Ishido N, Katsumata Y, Kagawa T, Hidaka Y, et al. The functional polymorphisms of VDR, GC, and CYP2R1 are involved in the pathogenesis of autoimmune thyroid diseases. Clin Exp Immunol. 2014;178(2):262–9. doi:10.1111/cei.12420.
Feng M, Li H, Chen SF, Li WF, Zhang FB. Polymorphisms in the vitamin D receptor gene and risk of autoimmune thyroid diseases: a meta-analysis. Endocrine. 2013;43(2):318–26. doi:10.1007/s12020-012-9812-y.
Giovinazzo S, Vicchio TM, Certo R, Alibrandi A, Palmieri O, Campenni A, et al. Vitamin D receptor gene polymorphisms/haplotypes and serum 25(OH)D3 levels in Hashimoto’s thyroiditis. Endocrine. 2016. doi:10.1007/s12020-016-0942-5.
Agmon-Levin N, Theodor E, Segal RM, Shoenfeld Y. Vitamin D in systemic and organ-specific autoimmune diseases. Clin Rev Allergy Immunol. 2013;45(2):256–66. doi:10.1007/s12016-012-8342-y.
Cooper GS, Stroehla BC. The epidemiology of autoimmune diseases. Autoimmun Rev. 2003;2(3):119–25.
Yasuda T, Okamoto Y, Hamada N, Miyashita K, Takahara M, Sakamoto F, et al. Serum vitamin D levels are decreased and associated with thyroid volume in female patients with newly onset Graves’ disease. Endocrine. 2012;42(3):739–41. doi:10.1007/s12020-012-9679-y.
Menconi F, Marcocci C, Marino M. Diagnosis and classification of Graves’ disease. Autoimmun Rev. 2014;13(4/5):398–402. doi:10.1016/j.autrev.2014.01.013.
Marino M, Latrofa F, Menconi F, Chiovato L, Vitti P. Role of genetic and non-genetic factors in the etiology of Graves’ disease. J Endocrinol Investig. 2015;38(3):283–94. doi:10.1007/s40618-014-0214-2.
Jurecka-Lubieniecka B, Bednarczuk T, Ploski R, Krajewska J, Kula D, Kowalska M, et al. Differences in gene–gene interactions in Graves’ disease patients stratified by age of onset. PLoS One. 2016;11(3):e0150307. doi:10.1371/journal.pone.0150307.
Wiersinga WM. Thyroid autoimmunity. Endocr Dev. 2014;26:139–57. doi:10.1159/000363161.
Wiersinga WM. Clinical relevance of environmental factors in the pathogenesis of autoimmune thyroid disease. Endocrinol Metab. 2016;31(2):213–22. doi:10.3803/EnM.2016.31.2.213.
Xu MY, Cao B, Yin J, Wang DF, Chen KL, Lu QB. Vitamin D and Graves’ disease: a meta-analysis update. Nutrients. 2015;7(5):3813–27. doi:10.3390/nu7053813.
Rotondi M, Chiovato L. Vitamin D deficiency in patients with Graves’ disease: probably something more than a casual association. Endocrine. 2013;43(1):3–5. doi:10.1007/s12020-012-9776-y.
Choi YM, Kim WG, Kim TY, Bae SJ, Kim HK, Jang EK, et al. Low levels of serum vitamin D3 are associated with autoimmune thyroid disease in premenopausal women. Thyroid Off J Am Thyroid Assoc. 2014;24(4):655–61. doi:10.1089/thy.2013.0460.
Van Belle TL, Gysemans C, Mathieu C. Vitamin D in autoimmune, infectious and allergic diseases: a vital player? Best Pract Res Clin Endocrinol Metab. 2011;25(4):617–32. doi:10.1016/j.beem.2011.04.009.
Zhou H, Xu C, Gu M. Vitamin D receptor (VDR) gene polymorphisms and Graves’ disease: a meta-analysis. Clin Endocrinol. 2009;70(6):938–45. doi:10.1111/j.1365-2265.2008.03413.x.
Cutolo M. Autoimmune polyendocrine syndromes. Autoimmun Rev. 2014;13(2):85–9. doi:10.1016/j.autrev.2013.07.006.
Lindmark E, Chen Y, Georgoudaki AM, Dudziak D, Lindh E, Adams WC, et al. AIRE expressing marginal zone dendritic cells balances adaptive immunity and T-follicular helper cell recruitment. J Autoimmun. 2013;42:62–70. doi:10.1016/j.jaut.2012.11.004.
Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96(1):53–538. doi:10.1210/jc.2010-2704.
Aspray TJ, Bowring C, Fraser W, Gittoes N, Javaid MK, Macdonald H, et al. National Osteoporosis Society vitamin D guideline summary. Age Aging. 2014;43(5):592–5. doi:10.1093/ageing/afu093.
Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911–30. doi:10.1210/jc.2011-0385.
Hewison M. An update on vitamin D and human immunity. Clin Endocrinol. 2012;76(3):315–25. doi:10.1111/j.1365-2265.2011.04261.x.
Mathieu C, Waer M, Casteels K, Laureys J, Bouillon R. Prevention of type I diabetes in NOD mice by nonhypercalcemic doses of a new structural analog of 1,25-dihydroxyvitamin D3, KH1060. Endocrinology. 1995;136(3):866–72. doi:10.1210/endo.136.3.7867594.
Antico A, Tampoia M, Tozzoli R, Bizzaro N. Can supplementation with vitamin D reduce the risk or modify the course of autoimmune diseases? A systematic review of the literature. Autoimmun Rev. 2012;12(2):127–36. doi:10.1016/j.autrev.2012.07.007.
Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr. 2003;77(1):204–10.
Heaney RP. The Vitamin D requirement in health and disease. J Steroid Biochem Mol Biol. 2005;97(1-2):13–9. doi:10.1016/j.jsbmb.2005.06.020.
Vieth R. Why the optimal requirement for Vitamin D3 is probably much higher than what is officially recommended for adults. J Steroid Biochem Mol Biol. 2004;89/90(1/5):575–9. doi:10.1016/j.jsbmb.2004.03.038.
Kriegel MA, Manson JE, Costenbader KH. Does vitamin D affect risk of developing autoimmune disease? A systematic review. Semin Arthritis Rheum. 2011;40(6):512–531 e8. doi:10.1016/j.semarthrit.2010.07.009.
Gloth III FM, Tobin JD, Sherman SS, Hollis BW. Is the recommended daily allowance for vitamin D too low for the homebound elderly? J Am Geriatr Soc. 1991;39(2):137–41.
Bischoff HA, Stahelin HB, Dick W, Akos R, Knecht M, Salis C, et al. Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. J Bone Miner Res. 2003;18(2):343–51. doi:10.1359/jbmr.2003.18.2.343.
Vieth R, Cole DE, Hawker GA, Trang HM, Rubin LA. Wintertime vitamin D insufficiency is common in young Canadian women, and their vitamin D intake does not prevent it. Eur J Clin Nutr. 2001;55(12):1091–7. doi:10.1038/sj.ejcn.1601275.
Munro I. Derivation of tolerable upper intake levels of nutrients. Am J Clin Nutr. 2001;74(6):865–7.
Vieth R. Critique of the considerations for establishing the tolerable upper intake level for vitamin D: critical need for revision upwards. J Nutr. 2006;136(4):1117–22.
Jones G. Pharmacokinetics of vitamin D toxicity. Am J Clin Nutr. 2008;88(2):582S–6S.
Zittermann A, Prokop S, Gummert JF, Borgermann J. Safety issues of vitamin D supplementation. Anticancer Agents Med Chem. 2013;13(1):4–10.
Lowe H, Cusano NE, Binkley N, Blaner WS, Bilezikian JP. Vitamin D toxicity due to a commonly available “over the counter” remedy from the Dominican Republic. J Clin Endocrinol Metab. 2011;96(2):291–5. doi:10.1210/jc.2010-1999.
Romagnoli E, Mascia ML, Cipriani C, Fassino V, Mazzei F, D’Erasmo E, et al. Short and long-term variations in serum calciotropic hormones after a single very large dose of ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) in the elderly. J Clin Endocrinol Metab. 2008;93(8):3015–20. doi:10.1210/jc.2008-0350.
Heaney RP, Recker RR, Grote J, Horst RL, Armas LA. Vitamin D(3) is more potent than vitamin D(2) in humans. J Clin Endocrinol Metab. 2011;96(3):E447–52. doi:10.1210/jc.2010-2230.
Authors contribution
B.A. and G.M. designed the study. B.A., G.M., L.B., C.M., C.V.V., L.M. and G.B. participated in the literature search and performed the selection of studies. B.A. wrote the Introduction, Methods and the Conclusion of the review, as well as the paragraphs on Addison’s disease and on vitamin D supplementation. C.V.V. supported B.A. in writing the Introduction and the paragraphs on vitamin D supplementation. G.M., S.S., N.B. and C.L.R. collaborated to the preparation of the manuscript providing relevant suggestions and corrections according to their long-lasting expertise in different research fields. L.B. wrote the paragraph on Grave’s disease and autoimmune polyendocrine syndromes. C.M. wrote the paragraph on diabetes mellitus. L.M. prepared the figure and wrote the paragraph on clinical and basic evidence. G.B. wrote the paragraph on Hashimoto thyroiditis. V.M.A., G.T. and G.B. contributed to the final version of the manuscript. A.C., A.P. and S.D.C. coordinated and supervised the preparation of the manuscript. All the authors reviewed and approved the final version of the manuscript.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Altieri, B., Muscogiuri, G., Barrea, L. et al. Does vitamin D play a role in autoimmune endocrine disorders? A proof of concept. Rev Endocr Metab Disord 18, 335–346 (2017). https://doi.org/10.1007/s11154-016-9405-9
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11154-016-9405-9
Keywords
- Vitamin D
- Autoimmunity
- Type 1 diabetes mellitus
- Addison’s disease
- Hashimoto’s thyroiditis
- Graves’ disease
- Autoimmune polyendocrine syndromes
- Environment
- Lifestyle