Immunologic Research

, Volume 61, Issue 1–2, pp 46–52 | Cite as

Vitamin D and autoimmune thyroid diseases: facts and unresolved questions

  • Giorgia Bizzaro
  • Yehuda Shoenfeld


Vitamin D deficiency (levels lower than 20 ng/ml) is becoming a global health problem, since it is increasingly represented even among healthy subjects. Vitamin D, as an environmental factor, is involved in many biological processes, like perception of chronic pain and response to infections. In recent years, evidence has emerged pointing to an involvement of vitamin D in the development of many autoimmune diseases, and a severe vitamin D deficiency has been especially demonstrated in patients affected with autoimmune thyroid disease (AITD). Low levels of vitamin D were found associated with antithyroid antibody presence, abnormal thyroid function, increased thyroid volume, increased TSH levels, and adverse pregnancy outcome in women with AITD. Vitamin D mediates its effect through binding to vitamin D receptor (VDR), which is harbored on many human immune cells, and in this way is able to modulate immune cells activity, triggering both innate and adaptive immune responses. As VDR gene polymorphisms were found to associate with AITD, the evidence links vitamin D deficiency to AITD either through gene polymorphism or by environmental factors (lack of dietary uptake and sun exposure). Vitamin D supplementation may be offered to AITD patients, but further research is needed to define whether it should be introduced in clinical practice.


Vitamin D Autoimmune diseases Graves’ disease Hashimoto’s thyroiditis Vitamin D supplementation Autoantibodies 


  1. 1.
    Holick MF. Vitamin D Deficiency. N Engl J Med. 2007;357:266–81.PubMedCrossRefGoogle Scholar
  2. 2.
    Holick MF. Resurrection of vitamin D deficiency and rickets. J Clin Invest. 2006;116:2062–72.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Holick MF, Garabedian M. Vitamin D: photobiology, metabolism, mechanism of action, and clinical applications. In: Favus MJ, editor. Primer on the metabolic bone diseases and disorders of mineral metabolism. 6th ed. Washington, DC: American Society for Bone and Mineral Research; 2006. p. 129–37.Google Scholar
  4. 4.
    Bouillon R. Vitamin D: from photosynthesis, metabolism, and action to clinical applications. In: DeGroot LJ, Jameson JL, editors. Endocrinology. Philadelphia: W.B. Saunders; 2001. p. 1009–28.Google Scholar
  5. 5.
    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;96:1911–30.PubMedCrossRefGoogle Scholar
  6. 6.
    Oren Y, Shapira Y, Agmon-Levin N, Kivity S, Zafrir Y, Altman A, et al. Vitamin D insufficiency in a sunny environment: a demographic and seasonal analysis. Isr Med Assoc J. 2010;12:751–6.PubMedGoogle Scholar
  7. 7.
    Holick MF. The Vitamin D epidemic and its health consequences. J Nutr. 2005;135:2739S–48S.PubMedGoogle Scholar
  8. 8.
    Mithal A, Wahl DA, Bonjour JP, Burckhardt P, et al. Global vitamin D status and determinants of hypovitaminosis D. Osteoporos Int. 2009;20:1807–20.PubMedCrossRefGoogle Scholar
  9. 9.
    Heidari B, Shirvani JS, Firouzjahi A, Heidari P, Hajian-Tilaki KO. Association between nonspecific skeletal pain and vitamin D deficiency. Int J Rheum Dis. 2010;13:340–6.PubMedCrossRefGoogle Scholar
  10. 10.
    McBeth J, Pye SR, O’Neill TW, Macfarlane GJ, Tajar A, Bartfai G, et al. Musculoskeletal pain is associated with very low levels of vitamin D in men: results from the European Male Ageing Study. Ann Rheum Dis. 2010;69:1448–52.PubMedCrossRefGoogle Scholar
  11. 11.
    Straube S, Derry S, Moore RA, McQuay HJ. Vitamin D for the treatment of chronic painful conditions in adults. Cochrane Database Syst Rev. 2010;(1):CD007771. doi: 10.1002/14651858.CD007771.pub2.
  12. 12.
    Wepner F, Scheuer R, Schuetz-Wieser B, Machacek P, Pieler-Bruha E, Cross HS, et al. Effects of vitamin D on patients with fibromyalgia syndrome: a randomized placebo-controlled trial. Pain. 2014;155:261–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Warner AE, Arnspiger SA. Diffuse musculoskeletal pain is not associated with low vitamin D levels or improved by treatment with vitamin D. J Clin Rheumatol. 2008;14:12–6.PubMedCrossRefGoogle Scholar
  14. 14.
    Feldman D, Krishnan AV, Swami S, Giovannucci E, Feldman BJ. The role of vitamin D in reducing cancer risk and progression. Nat Rev Cancer. 2014;14:342–57.PubMedCrossRefGoogle Scholar
  15. 15.
    Ajabshir S, Asif A, Nayer A. The effects of vitamin D on the renin-angiotensin system. J Nephropathol. 2014;3:41–3.PubMedCentralPubMedGoogle Scholar
  16. 16.
    Dobnig H, Pilz S, Scharnagl H, Renner W, Seelhorst U, Wellnitz B, et al. Independent association of low serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels with all-cause and cardiovascular mortality. Arch Intern Med. 2008;168:1340–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Peterlik M, Boonen S, Cross HS, Lamberg-Allardt C. Vitamin D and calcium insufficiency-related chronic diseases: an emerging world-wide public health problem. Int J Environ Res Public Health. 2009;6:2585–607.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    García de Tena J, Hachem Debek A, Hernández Gutiérrez C, Izquierdo Alonso JL. The role of vitamin D in chronic obstructive pulmonary disease, asthma and other respiratory diseases. Arch Bronconeumol. 2014;50:179–84.PubMedCrossRefGoogle Scholar
  19. 19.
    Patrick RP, Ames BN. Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism. FASEB J. 2014;28:2398–413.PubMedCrossRefGoogle Scholar
  20. 20.
    Mostafa GA, Al-Ayadhi LY. Reduced serum concentrations of 25-hydroxy vitamin D in children with autism: relation to autoimmunity. J Neuroinflammation. 2012;9:201.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Shoenfeld N, Amital H, Shoenfeld Y. The effect of melanism and vitamin D synthesis on the incidence of autoimmune disease. Nat Clin Pract Rheumatol. 2009;5:99–105.PubMedCrossRefGoogle Scholar
  22. 22.
    Arnson Y, Amital H, Shoenfeld Y. Vitamin D and autoimmunity: new aetiological and therapeutic considerations. Ann Rheum Dis. 2007;66:1137–42.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Arnson Y, Amital H, Agmon-Levin N, Alon D, Sánchez-Castañón M, López-Hoyos M, et al. Serum 25-OH vitamin D concentrations are linked with various clinical aspects in patients with systemic sclerosis: a retrospective cohort study and review of the literature. Autoimmun Rev. 2011;10:490–4.PubMedCrossRefGoogle Scholar
  24. 24.
    Szodoray P, Nakken B, Gaal J, Jomsson R, Szegedi A, Zold E, et al. The complex role of vitamin D in autoimmune diseases. Scand J Immunol. 2008;68:261–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Orbach H, Zandman-Goddard G, Amital H, Barak V, Szekanecz Z, Szucs G, et al. Novel biomarkers in autoimmune diseases: prolactin, ferritin, vitamin D, and TPA levels in autoimmune diseases. Ann N Y Acad Sci. 2007;1109:385–400.PubMedCrossRefGoogle Scholar
  26. 26.
    Shoenfeld Y, Zandman-Goddard G, Stojanovich L, Cutolo M, Amital H, Levy Y, et al. The mosaic of autoimmunity: hormonal and environmental factors involved in autoimmune diseases. Isr Med Assoc J. 2008;10:8–12.PubMedGoogle Scholar
  27. 27.
    Kivity S, Agmon-Levin N, Blank M, Shoenfeld Y. Infections and autoimmunity—friends or foes? Trends Immunol. 2009;30:409–14.PubMedCrossRefGoogle Scholar
  28. 28.
    Borella E, Nesher G, Israeli E, Shoenfeld Y. Vitamin D: a new anti-infective agent? Ann N Y Acad Sci. 2014;1317:76–83.PubMedCrossRefGoogle Scholar
  29. 29.
    Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006;311:1770–3.PubMedCrossRefGoogle Scholar
  30. 30.
    White JH. Vitamin D as an inducer of cathelicidin antimicrobial peptide expression: past, present and future. J Steroid Biochem Mol Biol. 2010;121:234–8.PubMedCrossRefGoogle Scholar
  31. 31.
    Shapira Y, Agmon-Levin N, Shoenfeld Y. Mycobacterium tuberculosis, autoimmunity, and vitamin D. Clin Rev Allergy Immunol. 2010;38:169–77.PubMedCrossRefGoogle Scholar
  32. 32.
    Barzilai O, Sherer Y, Ram M, Izhaky D, Anaya JM, Shoenfeld Y. Epstein–Barr virus and cytomegalovirus in autoimmune diseases: are they truly notorious? A preliminary report. Ann N Y Acad Sci. 2007;1108:567–77.PubMedCrossRefGoogle Scholar
  33. 33.
    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;31:92–6.PubMedGoogle Scholar
  34. 34.
    Cutolo M, Pizzorni C, Sulli A. Vitamin D endocrine system involvement in autoimmune rheumatic diseases. Autoimmun Rev. 2011;11:84–7.PubMedCrossRefGoogle Scholar
  35. 35.
    Amital H, Szekanecz Z, Szucs G, Danko K, Nagy E, Csepany T, et al. Serum concentrations of 25-OH vitamin D in patients with systemic lupus erythematosus (SLE) are inversely related to disease activity: is it time to routinely supplement patients with SLE with vitamin D? Ann Rheum Dis. 2010;69:1155–7.PubMedCrossRefGoogle Scholar
  36. 36.
    Miheller P, Muzes G, Hritz I, Lakatos G, Pregun I, Lakatos PL, et al. Comparison of the effects of 1,25 dihydroxyvitamin D and 25 hydroxyvitamin D on bone pathology and disease activity in Crohn’s disease patients. Inflamm Bowel Dis. 2009;15:1656–62.PubMedCrossRefGoogle Scholar
  37. 37.
    Rosati G. The prevalence of multiple sclerosis in the world: an update. Neurol Sci. 2001;22:117–39.PubMedCrossRefGoogle Scholar
  38. 38.
    Boucher BJ. Vitamin D insufficiency and diabetes risks. Curr Drug Targets. 2011;12:61–87.PubMedCrossRefGoogle Scholar
  39. 39.
    Cutolo M, Otsa K. Review: vitamin D, immunity and lupus. Lupus. 2008;17:6–10.PubMedCrossRefGoogle Scholar
  40. 40.
    Cutolo M, Otsa K, Paolino S, Yprus M, Veldi T, Seriolo B. Vitamin D involvement in rheumatoid arthritis and systemic lupus erythaematosus. Ann Rheum Dis. 2009;68:446–7.PubMedCrossRefGoogle Scholar
  41. 41.
    Agmon-Levin N, Blank M, Zandman-Goddard G, Orbach H, Meroni PL, Tincani A, et al. Vitamin D: an instrumental factor in the anti-phospholipid syndrome by inhibition of tissue factor expression. Ann Rheum Dis. 2011;70:145–50.PubMedCrossRefGoogle Scholar
  42. 42.
    Carvalho J, Blank M, Kiss E, Tarr T, Amital H, Shoenfeld Y. Antivitamin D vitamin D in SLE: preliminary results. Ann NY Acad Sci. 2007;1109:550–7.PubMedCrossRefGoogle Scholar
  43. 43.
    Mathieu C, Waer M, Laureys J, Rutgeerts O, Bouillon R. Prevention of autoimmune diabetes in NOD mice by 1,25 dihydroxyvitamin D3. Diabetologia. 1994;37:552–8.PubMedCrossRefGoogle Scholar
  44. 44.
    Cantorna MT, Hayes CE, DeLuca HF. 1,25-Dihydroxyvitamin D3 reversibly blocks the progression of relapsing encephalomyelitis, a model of multiple sclerosis. Proc Natl Acad Sci USA. 1996;93:7861–4.PubMedCentralPubMedCrossRefGoogle Scholar
  45. 45.
    Cantorna MT, Munsick C, Bemiss C, Mahon BD. 1,25-dihydroxycholecalciferol prevents and ameliorates symptoms of experimental murine inflammatory bowel disease. J Nutr. 2000;130:2648–52.PubMedGoogle Scholar
  46. 46.
    Mazokopakis EE, Kotsiris DA. Hashimoto’s autoimmune thyroiditis and vitamin D deficiency current aspects. Hell J Nucl Med. 2014;17:37–40.PubMedGoogle Scholar
  47. 47.
    Łacka K, Maciejewski A. Vitamin D in the etiopathogenesis of autoimmune thyroiditis. Pol Merkur Lekarski. 2013;34:281–5.PubMedGoogle Scholar
  48. 48.
    Misharin A, Hewison M, Chen CR, Lagishetty V, Aliesky HA, Mizutori Y, et al. Vitamin D deficiency modulates Graves’ hyperthyroidism induced in BALB/c mice by thyrotropin receptor immunization. Endocrinology. 2009;150:1051–60.PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    Chen W, Lin H, Wang M. Immune intervention effects on the induction of experimental autoimmune thyroiditis. J Huazhong Univ Sci Technol Med Sci. 2002;22(343–5):354.Google Scholar
  50. 50.
    Tamer G, Arik S, Tamer I, Coksert D. Relative vitamin D insufficiency in Hashimoto’s thyroiditis. Thyroid. 2011;21:891–6.PubMedCrossRefGoogle Scholar
  51. 51.
    Kivity S, Agmon-Levin N, Zisappl M, Shapira Y, Nagy EV, Dankó K, et al. Vitamin D and autoimmune thyroid diseases. Cell Mol Immunol. 2011;8:243–7.PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Bozkurt NC, Karbek B, Ucan B, Sahin M, Cakal E, Ozbek M, et al. The association between severity of vitamin D deficiency and Hashimoto’s thyroiditis. Endocr Pract. 2013;19:479–84.PubMedCrossRefGoogle Scholar
  53. 53.
    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;42:739–41.PubMedCentralPubMedCrossRefGoogle Scholar
  54. 54.
    Matalon ST, Blank M, Ornoy A, Shoenfeld Y. The association between antithyroid antibodies and pregnancy loss. Am J Reprod Immunol. 2001;45:72–7.PubMedCrossRefGoogle Scholar
  55. 55.
    Poppe K, Velkeniers B, Glinoer D. Thyroid disease and female reproduction. Clin Endocrinol (Oxf). 2007;66:309–21.CrossRefGoogle Scholar
  56. 56.
    Twig G, Shina A, Amital H, Shoenfeld Y. Pathogenesis of infertility and recurrent pregnancy loss in thyroid autoimmunity. J Autoimmun. 2012;38:J275–81.PubMedCrossRefGoogle Scholar
  57. 57.
    Shin DY, Kim KJ, Kim D, Hwang S, Lee EJ. Low serum vitamin D is associated with anti-thyroid peroxidase antibody in autoimmune thyroiditis. Yonsei Med J. 2014;55:476–81.PubMedCentralPubMedCrossRefGoogle Scholar
  58. 58.
    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 pre-menopausal women. Thyroid. 2014;24:655–61.PubMedCrossRefGoogle Scholar
  59. 59.
    Chailurkit LO, Aekplakorn W, Ongphiphadhanakul B. High vitamin D status in younger individuals is associated with low circulating thyrotropin. Thyroid. 2013;23:25–30.PubMedCrossRefGoogle Scholar
  60. 60.
    Zhang Q, Wang Z, Sun M, Cao M, Zhu Z, Fu Q, et al. Association of high vitamin d status with low circulating thyroid-stimulating hormone independent of thyroid hormone levels in middle-aged and elderly males. Int J Endocrinol. 2014;2014:631819.PubMedCentralPubMedGoogle Scholar
  61. 61.
    Mackawy AM, Al-Ayed BM, Al-Rashidi BM. Vitamin D deficiency and its association with thyroid disease. Int J Health Sci (Qassim). 2013;7:267–75.CrossRefGoogle Scholar
  62. 62.
    Goswami R, Marwaha RK, Gupta N, Tandon N, Sreenivas V, Tomar N, et al. Prevalence of vitamin D deficiency and its relationships with thyroid autoimmunity in Asian Indians: a community-based survey. Br J Nutr. 2009;102:382–6.PubMedCrossRefGoogle Scholar
  63. 63.
    Effraimidis G, Badenhoop K, Tijssen JG, Wiersinga WM. Vitamin D deficiency is not associated with early stages of thyroid autoimmunity. Eur J Endocrinol. 2012;167:43–8.PubMedCrossRefGoogle Scholar
  64. 64.
    Haussler MR, Whitfield GK, Haussler CA, Hsieh JC, Thompson PD, Selznick SH, et al. The nuclear vitamin D receptor: biological and molecular regulatory properties revealed. J Bone Miner Res. 1998;13:325–49.PubMedCrossRefGoogle Scholar
  65. 65.
    Feng M, Li H, Chen SF, Li WF, Zhang FB. Polymorphisms in the vitamin D receptor gene and risk of autoimmune thyroid disease: a meta-analysis. Endocrine. 2013;43:318–26.PubMedCrossRefGoogle Scholar
  66. 66.
    Kurylowicz A, Ramos-Lopez E, Bednarczuk T, Badenhoop K. Vitamin D-binding protein (DBP) gene polymorphism is associated with Graves’ disease and the vitamin D status in a Polish population study. Exp Clin Endocrinol Diabetes. 2006;114:329–35.PubMedCrossRefGoogle Scholar
  67. 67.
    Ban Y, Ban Y, Taniyama M, Katagiri T. Vitamin D receptor initiation codon polymorphism in Japanese patients with Graves’ disease. Thyroid. 2000;10:475–80.PubMedCrossRefGoogle Scholar
  68. 68.
    Bailey R, Cooper JD, Zeitels L, Smyth DJ, Yang JH, Walker NM, et al. Association of the vitamin D metabolism gene CYP27B1 with type 1 diabetes. Diabetes. 2007;56:2616–21.PubMedCentralPubMedCrossRefGoogle Scholar
  69. 69.
    Pani MA, Regulla K, Segni M, Krause M, Hofmann S, Hufner M, et al. Vitamin D 1α-hydroxylase (CYP1α) polymorphism in Graves’ disease, Hashimoto’s thyroiditis and type 1 diabetes mellitus. Eur J Endocrinol. 2002;146:777–81.PubMedCrossRefGoogle Scholar
  70. 70.
    Baeke F, Takiishi T, Korf H, Gysemans C, Mathieu C. Vitamin D modulator of the immune system. Curr Opin Pharmacol. 2010;10:482–96.PubMedCrossRefGoogle Scholar
  71. 71.
    Toubi E, Shoenfeld Y. The role of vitamin D in regulating immune responses. IMAJ. 2010;12:174–5.PubMedGoogle Scholar
  72. 72.
    Peelen E, Knippenberg S, Muris AH, Thewissen M, Smolders J, Tervaert JW, et al. Effects of vitamin D on the peripheral adaptive immune system: a review. Autoimmun Rev. 2011;10:733–43.PubMedCrossRefGoogle Scholar
  73. 73.
    Almerighi C, Sinistro A, Cavazza A, Ciaprini C, Rocchi G, Bergamini A. 1Alpha,25-dihydroxyvitamin D3 inhibits CD40L-induced pro-inflammatory and immunomodulatory activity in human monocytes. Cytokine. 2009;45:190–7.PubMedCrossRefGoogle Scholar
  74. 74.
    van Halteren AG, Tysma OM, van Etten E, Mathieu C, Roep BO. 1alpha,25-dihydroxyvitamin D3 or analogue treated dendritic cells modulate human autoreactive T cells via the selective induction of apoptosis. J Autoimmun. 2004;23:233–9.PubMedCrossRefGoogle Scholar
  75. 75.
    Penna G, Adorini L. 1 Alpha, 25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J Immunol. 2000;164:2405–11.PubMedCrossRefGoogle Scholar
  76. 76.
    Berer A, Stöckl J, Majdic O, Wagner T, Kollars M, Lechner K, et al. 1,25-Dihydroxyvitamin D(3) inhibits dendritic cell differentiation and maturation in vitro. Exp Hematol. 2000;28:575–83.PubMedCrossRefGoogle Scholar
  77. 77.
    Griffin MD, Lutz W, Phan VA, Bachman LA, McKean DJ, Kumar R. Dendritic cell modulation by 1alpha,25 dihydroxyvitamin D3 and its analogs: a vitamin D receptor-dependent pathway that promotes a persistent state of immaturity in vitro and in vivo. Proc Natl Acad Sci USA. 2001;98:6800–5.PubMedCentralPubMedCrossRefGoogle Scholar
  78. 78.
    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;270:701–8.PubMedCrossRefGoogle Scholar
  79. 79.
    van Etten E, Mathieu C. Immunoregulation by 1,25-dihydroxyvitamin D3: basic concepts. J Steroid Biochem Mol Biol. 2005;97:93–101.PubMedCrossRefGoogle Scholar
  80. 80.
    Mathieu C. Vitamin D and the immune system: getting it right. IBMS BonekEy. 2011;8:178–86.CrossRefGoogle Scholar
  81. 81.
    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;179:1634–47.PubMedCrossRefGoogle Scholar
  82. 82.
    Geldmeyer-Hilt K, Heine G, Hartmann B, Baumgrass R, Radbruch A, Worm M. 1,25- dihydroxyvitamin D3 impairs NF-κB activation in human naïve B cells. Biochem Biophys Res Commun. 2011;407:699–702.PubMedCrossRefGoogle Scholar
  83. 83.
    Souberbielle JC, Body JJ, Lappe JM, Plebani M, Shoenfeld Y, Wang TJ, et al. Vitamin D and musculoskeletal health, cardiovascular disease, autoimmunity and cancer: recommendations for clinical practice. Autoimmun Rev. 2010;9:709–15.PubMedCrossRefGoogle Scholar
  84. 84.
    Institute of Medicine (US). Committee to Review Dietary Reference Intakes for Vitamin D and Calcium. In: Ross AC, Taylor CL, Yaktine AL, Del Valle HB, editors. Dietary reference intakes for calcium and vitamin D. Washington, DC: National Academies Press; 2011.Google Scholar
  85. 85.
    Singh A, Kamen DL. Potential benefits of vitamin D for patients with systemic lupus erythematosus. Dermaoendocrinol. 2012;4:146–51.CrossRefGoogle Scholar
  86. 86.
    Theodoratou E, Tzoulaki I, Zgaga L, Ioannidis JPA. Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ. 2014;348:g2035.PubMedCentralPubMedCrossRefGoogle Scholar
  87. 87.
    Chowdhury R, Kunutsor S, Vitezova A, Oliver-Williams C, Chowdhury S, Kiefte-de-Jong JC, et al. Vitamin D and risk of cause specific death: systematic review and meta-analyses of observational cohort and randomised intervention studies. BMJ. 2014;348:g1903.PubMedCentralPubMedCrossRefGoogle Scholar
  88. 88.
    Bolland MJ, Grey A, Reid IR. Vitamin D supplements do not reduce mortality risk. BMJ. 2014;348:g2860.PubMedCrossRefGoogle Scholar
  89. 89.
    Kmietowicz Z. Vitamin D shows no clear evidence of benefits despite hundreds of studies. BMJ. 2014;348:g2489.PubMedCrossRefGoogle Scholar
  90. 90.
    Boucher BJ. Causal link between vitamin D deficiency and ill health still possible. BMJ. 2014;348:g2923.PubMedCrossRefGoogle Scholar
  91. 91.
    Pludowski P, Holick MF, Pilz S, Wagner CL, Hollis BW, Grant WB, et al. Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality-a review of recent evidence. Autoimmun Rev. 2013;12:976–89.PubMedCrossRefGoogle Scholar
  92. 92.
    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;12:127–36.PubMedCrossRefGoogle Scholar
  93. 93.
    Pelajo CF, Lopez-Benitez JM, Miller LC. Vitamin D and autoimmune rheumatologic disorders. Autoimmun Rev. 2010;9:507–10.PubMedCrossRefGoogle Scholar
  94. 94.
    Prietl B, Pilz S, Wolf M, Tomaschitz A, Obermayer-Pietsch B, Graninger W, et al. Vitamin D supplementation and regulatory T cells in apparently healthy subjects: vitamin D treatment for autoimmune diseases? Isr Med Assoc J. 2010;12:136–9.PubMedGoogle Scholar
  95. 95.
    Prietl B, Treiber G, Mader JK, Hoeller E, Wolf M, Pilz S, et al. High-dose cholecalciferol supplementation significantly increases peripheral CD4(+) Tregs in healthy adults without negatively affecting the frequency of other immune cells. Eur J Nutr. 2014;53:751–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.The Zabludowicz Center for Autoimmune DiseasesSheba Medical CenterTel-HashomerIsrael
  2. 2.Incumbent of the Laura Schwarz-Kip Chair for Research of Autoimmune Diseases, Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael

Personalised recommendations