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Vitamin D and multiple sclerosis: a critical review and recommendations on treatment

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Abstract

Multiple sclerosis (MS) is an immune-mediated and degenerative disease of nervous system, which affects mostly young adults. Vitamin D deficiency is a well-known environmental risk factor for MS and is considerable in terms of immediate clinical implications. In addition to its classical action on regulation of bone homeostasis, vitamin D may have a potent impact on cytokine profiles and neuro-inflammation. Given the immunomodulatory effects of vitamin D and its high rate of deficiency in MS patients, prescribing vitamin D is a remarkable issue in MS. The results from several experimental and clinical studies indicate that vitamin D supplementation may ameliorate the inflammation during the relapse phase and attenuate disease progression. We present the experimental and clinical studies, which assessed the effects of vitamin D on the pathophysiology, prevalence and management of MS. The authors also discuss current recommendations on prescription of this vitamin to MS patients.

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References

  1. Munger K, Levin L, Hollis B, Howard N, Ascherio A (2006) Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 296(23):2832

    Article  PubMed  CAS  Google Scholar 

  2. Giovannoni G (1997) The immunopathogenesis of multiple sclerosis. Baillière’s Clin Neurol 6(3):387

    CAS  Google Scholar 

  3. Ascherio A, Munger K (eds) (2008) Epidemiology of multiple sclerosis: from risk factors to prevention. Thieme-Stratton Inc., New York

  4. Ramagopalan SV, Ebers GC (2008) Genes for multiple sclerosis. The lancet 371(9609):283–285. doi:10.1016/S0140-6736(08)60145-2

    Google Scholar 

  5. Irizar H, Muñoz-Culla M, Zuriarran O, Goyenechea E, Castillo-Triviño T, Prada A et al (2011) HLA-DRB1* 15:01 and multiple sclerosis: a female association? Multiple Scler J

  6. Amirzargar A, Mytilineos J, Yousefipour A, Farjadian S, Scherer S, Opelz G et al (1998) HLA class II (DRB1, DQA1 and DQB1) associated genetic susceptibility in Iranian multiple sclerosis (MS) patients. Eur J Immunogenet 25(4):297–301

    Article  PubMed  CAS  Google Scholar 

  7. Sawcer S, Hellenthal G, Pirinen M, Spencer CC, Patsopoulos NA, Moutsianas L et al (2011) Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 476(7359):214–219

    Article  PubMed  CAS  Google Scholar 

  8. Handel A, Giovannoni G, Ebers G, Ramagopalan S (2010) Environmental factors and their timing in adult-onset multiple sclerosis. Nature Rev Neurol 6(3):156–166

    Google Scholar 

  9. Chaudhuri A (2005) Why we should offer routine vitamin D supplementation in pregnancy and childhood to prevent multiple sclerosis. Med Hypotheses 64(3):608–618

    Article  PubMed  CAS  Google Scholar 

  10. Holick MF (2004) Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am J Clin Nutr 80(6):1678S

    PubMed  CAS  Google Scholar 

  11. Arnson Y, Amital H, Shoenfeld Y (2007) Vitamin D and autoimmunity: new aetiological and therapeutic considerations. Ann Rheum Dis 66(9):1137

    Article  PubMed  CAS  Google Scholar 

  12. Cutolo M (2009) Vitamin D and autoimmune rheumatic diseases. Rheumatology 48(3):210

    Article  PubMed  CAS  Google Scholar 

  13. Holick MF, Krane SM, Potts J (1998) Calcium, phosphorus, and bone metabolism: calcium-regulating hormones. Harrisons Princ Intern Med:2214–2226

  14. Heaney RP (2008) Vitamin D criteria for safety and efficacy. Nutr Rev 66:S178–S181

    Article  PubMed  Google Scholar 

  15. Zittermann A (2003) Vitamin D in preventive medicine: are we ignoring the evidence? Br J Nutr 89(05):552–572

    Article  PubMed  CAS  Google Scholar 

  16. Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K et al (2008) Vitamin D deficiency and risk of cardiovascular disease. Circulation 117(4):503

    Article  PubMed  CAS  Google Scholar 

  17. Hollis BW (2004) Editorial: the determination of circulating 25-hydroxyvitamin D: no easy task. J Clin Endocrinol Metab 89(7):3149

    Article  PubMed  CAS  Google Scholar 

  18. Ross AC, Manson JAE, Abrams SA, Aloia JF, Brannon PM, Clinton SK et al (2011) 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 96(1):53

    Article  PubMed  CAS  Google Scholar 

  19. Staud R (2005) Vitamin D: more than just affecting calcium and bone. Curr Rheumatol Rep 7(5):356–364

    Article  PubMed  CAS  Google Scholar 

  20. Phinney KW (2008) Development of a standard reference material for vitamin D in serum. Am J Clin Nutr 88(2):511S

    PubMed  CAS  Google Scholar 

  21. Rafique I, Frederiksen J A (2010) complete literature survey: vitamin D and multiple sclerosis–what is clearly evident? Eur Neurol J 2(2):113–120

    Google Scholar 

  22. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP et al (2011) Evaluation, treatment, and prevention of vitamin d deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 96(7):1911

    Article  PubMed  CAS  Google Scholar 

  23. Hanwell HEC, Banwell B (2011) Assessment of evidence for a protective role of vitamin D in multiple sclerosis. Biochim et Biophys Acta (BBA)-Mol Basis Dis 1812(2):202–212

    Google Scholar 

  24. Penna G, Adorini L (2000) 1, 25-Dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J Immunol 164(5):2405

    PubMed  CAS  Google Scholar 

  25. Ponsonby AL, Lucas R, Mei IAF (2005) UVR, vitamin D and three autoimmune diseases—multiple sclerosis, type 1 diabetes, rheumatoid arthritis. Photochem Photobiol 81(6):1267–1275

    Article  PubMed  CAS  Google Scholar 

  26. Lemire JM (1995) Immunomodulatory actions of 1, 25-dihydroxyvitamin D3. J Steroid Biochem Mol Biol 53(1–6):599–602

    Article  PubMed  CAS  Google Scholar 

  27. van Etten E, Gysemans C, Branisteanu D, Verstuyf A, Bouillon R, Overbergh L et al (2007) Novel insights in the immune function of the vitamin D system: synergism with interferon-beta. J Steroid Biochem Mol Biol 103(3–5):546–551

    Article  PubMed  Google Scholar 

  28. van Halteren AGS, Tysma OM, van Etten E, Mathieu C, Roep BO (2004) 1 [alpha], 25-dihydroxyvitamin D3 or analogue treated dendritic cells modulate human autoreactive T cells via the selective induction of apoptosis. J Autoimmun 23(3):233–239

    Article  PubMed  Google Scholar 

  29. Mark BL, Carson JAS (2006) Vitamin D and autoimmune disease–implications for practice from the multiple sclerosis literature. J Am Diet Assoc 106(3):418–424

    Article  PubMed  CAS  Google Scholar 

  30. Pierrot-Deseilligny C (2009) Clinical implications of a possible role of vitamin D in multiple sclerosis. J Neurol 256(9):1468–1479

    Article  PubMed  CAS  Google Scholar 

  31. Correale J, Ysrraelit M, Gaitán M (2009) Immunomodulatory effects of Vitamin D in multiple sclerosis. Brain 132(5):1146

    Article  PubMed  Google Scholar 

  32. Knippenberg S, Smolders J, Thewissen M, Peelen E, Tervaert JWC, Hupperts R et al (2011) Effect of vitamin D3 supplementation on peripheral B cell differentiation and isotype switching in patients with multiple sclerosis. Multiple Scler J

  33. Smolders J, Peelen E, Thewissen M, Tervaert JWC, Menheere P, Hupperts R et al (2010) Safety and T cell modulating effects of high dose vitamin D3 supplementation in multiple sclerosis. PLoS One 5(12):e15235

    Article  PubMed  CAS  Google Scholar 

  34. Mahon B, Gordon S, Cruz J, Cosman F, Cantorna M (2003) Cytokine profile in patients with multiple sclerosis following vitamin D supplementation. J Neuroimmunol 134(1–2):128–132

    Article  PubMed  CAS  Google Scholar 

  35. Ebers G, Sadovnick A (1993) The geographic distribution of multiple sclerosis: a review. Neuroepidemiology 12(1):1–5

    Article  PubMed  CAS  Google Scholar 

  36. Acheson E, Bachrach C, Wright F (1960) Some comments on the relationship of the distribution of multiple sclerosis to latitude, solar radiation, and other variables. Acta Psychiatr Scand 35(S147):132–147

    Google Scholar 

  37. Smolders J (2011) Vitamin D and multiple sclerosis: correlation, causality, and controversy

  38. Poppe AY, Wolfson C, Zhu B (2008) Prevalence of multiple sclerosis in Canada: a systematic review. Can J Neurol Sci 35(5):593–601

    PubMed  Google Scholar 

  39. Grønlie SA, Myrvoll E, Hansen G, Grønning M, Mellgren SI (2000) Multiple sclerosis in North Norway, and first appearance in an indigenous population. J Neurol 247(2):129–133

    Google Scholar 

  40. Fernandes de Abreu DA, Landel V, Féron F (2011) Seasonal, gestational and postnatal influences on multiple sclerosis: the beneficial role of a vitamin D supplementation during early life. J Neurol Sci 311(1–2):64–68

    Article  PubMed  CAS  Google Scholar 

  41. Van der Mei I, Ponsonby A, Dwyer T, Blizzard L, Simmons R, Taylor B et al (2003) Past exposure to sun, skin phenotype, and risk of multiple sclerosis: case-control study. BMJ 327(7410):316

    Article  PubMed  Google Scholar 

  42. Kampman M, Wilsgaard T, Mellgren S (2007) Outdoor activities and diet in childhood and adolescence relate to MS risk above the Arctic Circle. J Neurol 254(4):471–477

    Article  PubMed  CAS  Google Scholar 

  43. Noonan F, Bucana C, Sauder D, De Fabo E (1984) Mechanism of systemic immune suppression by UV irradiation in vivo. II. The UV effects on number and morphology of epidermal Langerhans cells and the UV-induced suppression of contact hypersensitivity have different wavelength dependencies. J Immunol 132(5):2408

    PubMed  CAS  Google Scholar 

  44. Hanneman K, Cooper K, Baron E (2006) Ultraviolet immunosuppression: mechanisms and consequences. Dermatol Clin 24(1):19

    Article  PubMed  CAS  Google Scholar 

  45. Beretich B, Beretich T (2009) Explaining multiple sclerosis prevalence by ultraviolet exposure: a geospatial analysis. Multiple Scler 15(8):891

    Article  CAS  Google Scholar 

  46. Mirzaei F, Michels KB, Munger K, O’Reilly E, Chitnis T, Forman MR et al Gestational vitamin D and the risk of multiple sclerosis in offspring. Ann Neurol 70(1):30–40

  47. Soilu-Hänninen M, Airas L, Mononen I, Heikkilä A, Viljanen M, Hänninen A (2005) 25-Hydroxyvitamin D levels in serum at the onset of multiple sclerosis. Multiple Scler 11(3):266

    Article  Google Scholar 

  48. Munger K, Zhang S, O’Reilly E, Hernan M, Olek M, Willett W et al (2004) Vitamin D intake and incidence of multiple sclerosis. Neurology 62(1):60

    Article  PubMed  CAS  Google Scholar 

  49. Munger K, Chitnis T, Frazier A, Giovannucci E, Spiegelman D, Ascherio A (2011) Dietary intake of vitamin D during adolescence and risk of multiple sclerosis. J Neurol 258(3):479–485

    Article  PubMed  CAS  Google Scholar 

  50. Simon K, Munger K (2010) Polymorphisms in vitamin D metabolism related genes and risk of multiple sclerosis. Multiple Scler 16(2):133

    Article  CAS  Google Scholar 

  51. Wüthrich R, Rieder H (1970) The seasonal incidence of multiple sclerosis in Switzerland. Eur Neurol 3(5):257

    Article  PubMed  Google Scholar 

  52. Tremlett H, Van der Mei I, Pittas F, Blizzard L, Paley G, Mesaros D et al (2008) Monthly ambient sunlight, infections and relapse rates in multiple sclerosis. Neuroepidemiology 31(4):271–279

    Article  PubMed  Google Scholar 

  53. Embry A, Snowdon L, Vieth R (2000) Vitamin D and seasonal fluctuations of gadolinium enhancing magnetic resonance imaging lesions in multiple sclerosis. Ann Neurol 48(2):271–272

    Article  PubMed  CAS  Google Scholar 

  54. Cantorna MT, Hayes CE, DeLuca HF (1996) 1, 25-Dihydroxyvitamin D3 reversibly blocks the progression of relapsing encephalomyelitis, a model of multiple sclerosis. Proc Natl Acad Sci USA 93(15):7861

    Article  PubMed  CAS  Google Scholar 

  55. Spach KM, Pedersen LB, Nashold FE, Kayo T, Yandell BS, Prolla TA et al (2004) Gene expression analysis suggests that 1,25-dihydroxyvitamin D3 reverses experimental autoimmune encephalomyelitis by stimulating inflammatory cell apoptosis. Physiol Genomics 18(2):141–151

    Article  PubMed  CAS  Google Scholar 

  56. Orton S, Morris A, Herrera B, Ramagopalan S, Lincoln M, Chao M et al (2008) Evidence for genetic regulation of vitamin D status in twins with multiple sclerosis. Am J Clin Nutr 88(2):441

    PubMed  CAS  Google Scholar 

  57. Smolders J, Damoiseaux J, Menheere P, Tervaert J, Hupperts R (2009) Association study on two vitamin D receptor gene polymorphisms and vitamin D metabolites in multiple sclerosis. Ann NY Acad Sci 1173(1):515–520

    Article  PubMed  CAS  Google Scholar 

  58. Mowry E, Krupp L, Milazzo M, Chabas D, Strober J, Belman A et al (2010) Vitamin D status is associated with relapse rate in pediatric-onset multiple sclerosis. Ann Neurol 67(5):618–624

    PubMed  CAS  Google Scholar 

  59. Goldberg P, Fleming M, Picard E (1986) Multiple sclerosis: decreased relapse rate through dietary supplementation with calcium, magnesium and vitamin D. Med Hypotheses 21(2):193–200

    Article  PubMed  CAS  Google Scholar 

  60. Wingerchuk D, Lesaux J, Rice G, Kremenchutzky M, Ebers G (2005) A pilot study of oral calcitriol (1,25-dihydroxyvitamin D3) for relapsing–remitting multiple sclerosis. Br Med J 76(9):1294

    CAS  Google Scholar 

  61. Burton J, Kimball S, Vieth R, Bar-Or A, Dosch H, Cheung R et al (2010) A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis. Neurology 74(23):1852

    Article  PubMed  CAS  Google Scholar 

  62. Kampman MT, Steffensen LH, Mellgren SI, Jørgensen L (2012) Effect of vitamin D3 supplementation on relapses, disease progression and measures of function in persons with multiple sclerosis: exploratory outcomes from a double-blind randomised controlled trial. Multiple Scler [Epub ahead of print]

  63. Soilu-Hänninen M, Ãivo J, Lindström BM, Elovaara I, Sumelahti ML, Färkkilä M et al (2012) A randomised, double blind, placebo controlled trial with vitamin D3 as an add on treatment to interferon β-1b in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 83(5):565–571

    Article  PubMed  Google Scholar 

  64. van Etten E, Gysemans C, Branisteanu DD, Verstuyf A, Bouillon R, Overbergh L et al (2007) Novel insights in the immune function of the vitamin D system: synergism with interferon-beta. J Steroid Biochem Mol Biol 103(3):546–551

    Article  PubMed  Google Scholar 

  65. Nieves J, Cosman F, Herbert J, Shen V, Lindsay R (1994) High prevalence of vitamin D deficiency and reduced bone mass in multiple sclerosis. Neurology 44(9):1687

    Article  PubMed  CAS  Google Scholar 

  66. Hiremath G, Cettomai D, Baynes M, Ratchford J, Newsome S, Harrison D et al (2009) Vitamin D status and effect of low-dose cholecalciferol and high-dose ergocalciferol supplementation in multiple sclerosis. Multiple Scler 15(6):735

    Article  CAS  Google Scholar 

  67. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK et al (2011) 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 96(1):53–58

    Article  PubMed  CAS  Google Scholar 

  68. Pierrot-Deseilligny C, Souberbielle JC (2011) Widespread vitamin D insufficiency: a new challenge for primary prevention, with particular reference to multiple sclerosis. La Press Med

  69. Adams JS, Hewison M (2010) Update in vitamin D. J Clin Endocrinol Metab 95(2):471

    Article  PubMed  Google Scholar 

  70. Haroon M, Regan MJ (2010) Vitamin D deficiency: the time to ignore it has passed. Int J Rheum Dis 13(4):318–323

    Article  PubMed  Google Scholar 

  71. Dawson-Hughes B, Heaney RP, Holick MF, Lips P, Meunier PJ, Vieth R (2005) Estimates of optimal vitamin D status. Osteoporos Int 16(7):713–716

    Article  PubMed  CAS  Google Scholar 

  72. Soilu-Hänninen M, Laaksonen M, Laitinen I, Erälinna J, Lilius E, Mononen I (2008) A longitudinal study of serum 25-hydroxyvitamin D and intact parathyroid hormone levels indicate the importance of vitamin D and calcium homeostasis regulation in multiple sclerosis. J Neurol Neurosurg Psychiatry 79(2):152

    Article  PubMed  Google Scholar 

  73. Cantorna M, Mahon B (2004) Mounting evidence for vitamin D as an environmental factor affecting autoimmune disease prevalence. Exp Biol Med 229(11):1136–1142

    CAS  Google Scholar 

  74. Kimball S, Ursell M, O’Connor P, Vieth R (2007) Safety of vitamin D3 in adults with multiple sclerosis. Am J Clin Nutr 86(3):645

    PubMed  CAS  Google Scholar 

  75. Mosayebi G, Ghazavi A, Ghasami K, Jand Y, Kokhaei P (2011) Therapeutic effect of vitamin D3 in multiple sclerosis patients. Immunol Investig 40(6):627–639

    Article  CAS  Google Scholar 

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Acknowledgments

The authors would like to express their gratitude to Professor Abdolmohamad Rostami for constructive comments. We are also so grateful to Ms. Katherine Regan for kindly editing the manuscript.

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Authors and Affiliations

  1. Department of Neurology, University of California, San Francisco, USA

    Alireza Faridar

  2. Brain and Spinal Injury Research Center, Tehran University of Medical Sciences, Sina Hospital, Hassan Abad Square, Tehran, Iran

    Ghazaleh Eskandari & Amirreza Azimi

  3. SinaMS Research Center, Brain and Spinal Injury Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Mohammad Ali Sahraian

  4. Department of Neurology, LSU Health Sciences Center, Shreveport, LA, 71130, USA

    Alireza Minagar

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  1. Alireza Faridar
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  2. Ghazaleh Eskandari
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  3. Mohammad Ali Sahraian
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  5. Amirreza Azimi
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Correspondence to Amirreza Azimi.

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A. Faridar, G. Eskandari contributed equally to this work.

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Faridar, A., Eskandari, G., Sahraian, M.A. et al. Vitamin D and multiple sclerosis: a critical review and recommendations on treatment. Acta Neurol Belg 112, 327–333 (2012). https://doi.org/10.1007/s13760-012-0108-z

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