Contribution of vitamin D insufficiency to the pathogenesis of multiple sclerosis

Therapeutic Advances in Neurological Disorders

Volumn 6, Issue 2, 2013, Pages 81-116

  Pierrot Deseilligny, Charles ^a   Souberbielle, Jean Claude ^b  

^a ASSISTANCE PUBLIQUE HÔPITAUX DE PARIS   (France)

^b HÔPITAL NECKER ENFANTS MALADES   (France)

Author keywords

Epstein Barr virus; genetics; multiple sclerosis; smoking; vitamin D

Indexed keywords

VITAMIN D;

EPSTEIN BARR VIRUS INFECTION; GENETIC RISK; HUMAN; MULTIPLE SCLEROSIS; NEUROPATHOLOGY; PRIORITY JOURNAL; RELAPSE; REVIEW; RISK FACTOR; SMOKING; VITAMIN D DEFICIENCY; VITAMIN METABOLISM;

EID: 84874506801     PISSN: 17562856     EISSN: 17562864     Source Type: Journal    
DOI: 10.1177/1756285612473513     Document Type: Review

References (370)

1. 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 Suppl 35: 37–42.
2. Adorini L. Penna G. (2008) Control of autoimmune diseases by the vitamin D endocrine system. Nat Clin Pract Rheumatol 4: 404–412.
3. Agliardi C. Guerini F. Saresella M. Caputo D. Leone M. Zanzottera M. et al. (2011) Vitamin D receptor (VDR) gene SNPs influence VDR expression and modulate protection from multiple sclerosis in HLA-DRB1*15 positive individuals. Brain Behav Immun 25: 1460–1467.
4. Allen A. Kelly S. Basdeo S. Kinsella K. Muready K. Mills K. et al. (2012) A pilot study of immunological effects of high-dose vitamin D in healthy volunteers. Mult Scler 18: 1797-1800.
5. Alloza I. Otaequi D. de Lapuente A. Antiqüedad A. Varadé G. Núnez C. et al. (2012) ANKRD 55 and DHCR 7 are novel multiple sclerosis risk loci. Genes Immun 13: 253–257.
6. Aloisi F. Serafini B. Magliozzi R. Howell O. Reynolds R. (2010) Detection of Epstein–Barr virus and B-cell follicles in the multiple sclerosis brain: what you find depends on how and where you look. Brain 133: 1–5.
7. Alonso A. Hernan M. (2008) Temporal trends in the incidence of multiple sclerosis: a systematic review. Neurology 7: 129–135.
8. ANZgene and the Australia and New Zealand Multiple Sclerosis Genetics Consortium (2009) Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20. Nat Genet 41: 824–828.
9. Armas L. Dowell S. Akhter M. Duthuluru S. Huerter C. Hollis B. et al. (2007) Ultraviolet-B radiation increases serum 25-hydroxyvitamin D levels: the effect of UVB dose and skin colour. J Am Acad Dermatol 57: 588–593.
10. Ascherio A. Munger K. (2007 a) Environmental risk factors for multiple sclerosis. Part I: the role of infection. Ann Neurol 61: 288–299.
11. Ascherio A. Munger K. (2007 b) Environmental risk factors for multiple sclerosis. Part II: non-infectious factors. Ann Neurol 61: 504–513.
12. Ascherio A. Munger K. Lünemann J. (2012 a) The initiation and prevention of multiple sclerosis. Nat Rev Neurol 8: 602–612.
13. Ascherio A. Munger K. Simon K. (2010) Vitamin D and multiple sclerosis. Lancet Neurol 9: 599–612.
14. Ascherio A. Munger K. Simon C. Kappos L. Polman C. Freedman M. et al. (2012 b) Serum 25-hydroxyvitamin D concentrations among patients in BENEFIT predicts conversion to multiple sclerosis, MRI lesions, and brain volume loss. Mult Scler 18(Suppl. 4): 374–375.
15. Axtell R. de Jong B. Boniface K. van der Voort L. Bhat R. de Samo P. et al. (2010) T helper type 1 and 17 cells determine efficacy of interferon-β in multiple sclerosis and experimental encephalomyelitis. Nat Med 16: 406–412.
16. Azizi E. Pavlotski F. Kudish A. Flint P. Solomon A. Lerman Y. et al. (2012) Serum levels of 25-hydroxy-vitamin D 3 among sun-protected outdoor workers in Israel. Photochem Photobiol 88: 1507–1512.
17. Bäärnhielm M. Hedström A. Kockum I. Sundqvist E. Gustafsson S. Hillert J. et al. (2012) Sunlight is associated with decreased MS risk: no interaction with HLA-DRB1*15. Eur J Neurol 19: 955–962.
18. Baas D. Prufer K. Ittel M. Kuchler-Boop S. Labourdette G. Sarlieve L. Brachet P. (2000) Rat oligodendrocytes express vitamin D (3) receptor and respond to 1,25-dihydroxyvitamin (D)3. Glia 1: 59–68.
19. Baeke F. Korf H. Overbergh H. van Etten E. Verstuyf A. Gysemans C. Mathieu C. (2010) Human T lymphocytes are direct targets of 1,25-dihydroxyvitamin D 3 in the immune system. J Steriod Biochem Mol Biol 121: 221–227.
20. Banwell B. Bar-Or A. Arnold D. Sadovnick D. Narayanan S. McGowan S. et al. (2011) Clinical, environmental, and genetic determinants of multiple sclerosis in children with acute demyelination: a prospective national cohort study. Lancet Neurol 10: 436–445.
21. Barger-Lux M. Heaney R. (2002) Effects of above average summer sun exposure on serum 25-hydroxyvitamin d and calcium absorption. J Clin Endocrinol Metab 87: 4952–4956.
22. Bartosik-Psujek H. Tabarkiewicz J. Pocisnska K. Stelmasiak Z. Rolinski J. (2010) Immunomodulatory effects of vitamin D on monocyte-derived dendritic cells in multiple sclerosis. Mult Scler 16: 1513–1516.
23. Bayes H. Weir C. O'Leary C. (2009) Timing of birth and risk of multiple sclerosis in the Scottish population. Eur Neurol 63: 36–40.
24. Becklund B. Severson K. Vang S. Deluca H. (2010) UV radiation suppresses experimental autoimmune encephalomyelitis independent of vitamin D production. Proc Natl Acad Sci U S A 107: 6418–6423.
25. Beretich B. Beretich T. (2009) Explaining multiple sclerosis prevalence by ultraviolet exposure: a geospatial analysis. Mult Scler 15: 891–898.
26. Berlanga-Taylor A. Disanto G. Ebers G. Ramagopalan S. (2011) Vitamin D-gene interactions in multiple sclerosis. J Neurol Sci 311: 32–36.
27. Bhalla A. Amento E. Clemens T. Holick M. Krane S. (1983) Specific high-affinity receptors for 1,25-dihydroxivitamin D 3 in human peripheral blood mononuclear cells: presence in monocytes and induction in T lymphocytes following activation. J Clin Endocrinol Metab 57: 1308–1310.
28. Binkley N. Krueger D. (2008) Evaluation and correction of low vitamin D status. Curr Osteoporos Rep 6: 95–99.
29. Binkley N. Novotny R. Krueger D. Kawahara T. Daida Y. Lensmeyer G. et al. (2007) Low vitamin D status despite abundant sun exposure. J Endocrinol Metab 92: 2130–2135.
30. Bischoff-Ferrari H. Dawson-Hughes B. Staehelin H. Orav J. Stuck A. Theiler R. et al. (2009 a). Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. BMJ 339: b3692.
31. Bischoff-Ferrari H. Dietrich T. Orav E. Dawson-Hughes B. (2004) Positive association between 25-hydroxyvitamin D level and bone mineral density: a population-based study of younger and older adults. Am J Med 116: 634–639.
32. Bischoff-Ferrari H. Giovannucci E. Willett W. Dietrich T. Dawson-Hughes B. (2006) Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr 84: 18–28.
33. Bischoff-Ferrari H. Willett W. Orav E. Lips P. Meunie P. Lyons R. et al. (2012) A pooled analysis of vitamin D requirements for fracture prevention. New Engl J Med 367: 40–49.
34. Bischoff-Ferrari H. Willett W. Wong J. Stuck A. Staehelin B. Orav E. et al. (2009 b) Prevention of non-vertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Arch Intern Med 169: 551–561.
35. Bodnar L. Catov J. Simhan H. Holick M. Powers R. Roberts J. (2007) Maternal vitamin D deficiency increases the risk of preeclampsia. J Clin Endocrinol Metab 92: 3517–3522.
36. Boiko A. Deomina T. Favorova O. Gusev E. Sudomoina M. Turestkaya R. (1995) Epidemiology of multiple sclerosis in Russia and other countries of the former Soviet Union: investigations of environmental and genetic factors. Acta Neurol Scand Suppl 161: 71–76.
37. Boonstra A. Barrat F. Crain C. Heath V. Savekoul H. O'Garra A. (2001) 1alpha,25-Dihydroxyvitamin d 3 has a direct effect on naïve CD4(+) T cells to enhance the development of Th 2 cells. J Immunol 167: 4974–4980.
38. Borradale D. Kimlin M. (2009) Vitamin D in health and disease: an insight into traditional functions and new roles of ‘sunshine vitamin’. Nutr Res Rev 10: 1–19.
39. Bruce D. Yu S. Ooi J. Cantorna M. (2011) Converging pathways lead to overproduction of IL-17 in the absence of vitamin D signalling. Int Immunol 23: 519–528.
40. Burrell A. Handel A. Ramagopalan S. Ebers G. Morahan J. (2011) Epigenetic mechanisms in multiple sclerosis and the major histocompatibility complex (MHC). Discov Med 11: 187–196.
41. Burton J. Kimball S. Vieth R. Bar-Or A. Dosch H. Cheug R. et al. (2010) A phase I / II dose escalation trial of vitamin D 3 and calcium in multiple sclerosis. Neurology 74: 1852–1859.
42. Bushnell S. Zhao Z. Stebbins C. Cadavid D. Buko A. Whalley E. et al. (2012) Serum IL-17F does not predict poor response to IM IFNβ-1a in relapsing-remitting MS. Neurology 79: 531–537.
43. Calvo M. Whiting S. Barton C. (2004) Vitamin D fortification in the United States and Canada: current status and data needs. Am J Clin Nutr 80(Suppl.): 1710S–1716S.
44. Cantorna M. (2006) Vitamin D and its role in immunology: multiple sclerosis and inflammatory bowel disease. Prog Biophys Mol Biol 92: 60–64.
45. Cantorna M. (2008) Vitamin D and multiple sclerosis: an update. Nutr Rev 66(10 Suppl. 2): S135–S138.
46. Cantorna M. Hayes C. de Luca H. (1996) 1,25-Dihydoxyvitamin D 3 reversibly blocks the progression of encephalomyelitis, a model of multiple sclerosis. Proc Natl Acad Sci U S A 93: 7861–7864.
47. Cantorna M. Humpal-Winter J. de Luca H. (1999) Dietary calcium is a major factor in 1,25-dihydroxycholecalciferol suppression of experimental autoimmune encephalomyelitis in mice. J Nutr 129: 1966–1971.
48. Cantorna M. Woodward W. Hayes C. de Luca H. (1998) 1,25-Dihydroxyvitamin D 3 is a positive regulator for the two anti-encephalitogenic cytokines TGF-beta 1 and IL-4. J Immunol 160: 5314–5319.
49. Cantorna M. Zhao J. Zhang L. (2012) Vitamin D, invariant natural killer T-cells and experimental autoimmune disease. Proc Nutr Soc 71: 62–66.
50. Carlens C. Hergens M. Grunewald J. Ekbom A. Eklund A. Hoglund C. et al. (2010) Smoking, use of moist snuff, and risk of chronic inflammatory diseases. Am J Respir Crit Care Med 181: 1217–1222.
51. Carmel A. Shieh A. Bang H. Bockman R. (2012). The 25(OH)D level needed to maintain a favourable bisphosphonate response is >33 ng/mL. Osteoporos Int 23: 2479–2487.
52. Cashman K. Fitzgerald A. Kiely M. Seamans K. (2011) A systematic review and meta-regression analysis of the vitamin D intake-serum 25-hydroxyvitamin D relationship to inform European recommendations. Br J Nutr 106: 16171–627.
53. Ceglia L. Harris S. (2012) Vitamin D and its role in skeletal muscle. Calcif Tissue Int 12 September (Epub ahead of print).
54. Chang J. Cha H. Lee D. Seo K. Kweon M. (2010) 1,25-Dihydroxyvitamin D 3 inhibits the differentiation and migration of T(H)17 cells to protect against experimental autoimmune encephalomyelitis. PlosOne 5: e12925.
55. Chao M. Herrera B. Ramagopalan S. Deluca G. Handunnetthi L. Orton S. et al. (2010) Parent-of-origin effects at the major histocompatility complex in multiple sclerosis. Hum Mol Genet 19: 3679–3689.
56. Chao M. Ramagopalan S. Herrera B. Lincoln M. Dyment D. Ebers G. (2009) Epigenetics in multiple sclerosis susceptibility: difference in transgenerational risk localizes to the major histocompatibility complex. Hum Mol Genet 18: 261–266.
57. Chapuy M. Preziosi P. Maamer M. Arnaud S. Galan P. Hercberg S. et al. (1996) Prevalence of vitamin D insufficiency in an adult normal population. Osteoporosis Int 7: 439–443.
58. Chen S. Sims G. Chen X. Gu Y. Chen S. Lipsky P. (2007) Modulatory effect of 1,25-dihydroxyvitamin D 3 on human B cell differentiation. J Immunol 179: 1634–1647.
59. Cocco E. Meloni A. Murru M. Corongiu D. Tranquilli S. Fadda E. et al. (2012) Vitamin D responsive elements within the HLA-DRB1 promoter region in Sardinian multiple sclerosis alleles. PloS ONE 7: e41678.
60. Correale J. Ysrraelit M. Gaitan M. (2009) Immunomodulatory aspects of vitamin D in multiple sclerosis. Brain 132: 1146–1160.
61. Correale J. Ysrraelit M. Gaitan M. (2010) Gender differences in 1,25 dihydroxyvitamin D 3 immunomodulatory effects in multiple sclerosis patients and healthy subjects. J Immunol 185: 4948–4958.
62. Cox M. Ban M. Bowden N. Baker A. Scott R. Lechner-Scott J. (2012) Potential association of vitamin D receptor polymorphism Taq 1 with multiple sclerosis. Mult Scler 18: 16–22.
63. Dabbaghmanesh M. Yousefipour G. (2011) Bone loss with multiple sclerosis: effect of glucocorticoid use and functional status. Iran Red Crescent Med J 13: 9–14.
64. Dawson-Hughes B. Heaney R. Holick M. Lips P. Meunier P. Vieth R. (2005) Estimates of optimal vitamin D status. Osteoporos Int 16: 713–716.
65. Dean G. Elian M. (1997) Age at immigration to England of Asian and Caribbean immigrants and the risk of developing multiple sclerosis. J Neurol Neurosurg Psychiatry 63: 565–568
66. Décard B. von Ahsen N. Grunwald T. Streit F. Stoet A. Niggermier P. et al. (2012) Low vitamin D and elevated immunoreactivity against Epstein-Barr virus before first clinical manifestation of multiple sclerosis. J Neurol Neurosurg Psychiatry 83: 1170–1173.
67. de Jager P. Simon K. Munger K. Rioux J. Hafler D. Ascherio A. (2008) Integrating risk factors. HLA-DRB1*1501 and Epstein-Barr virus in multiple sclerosis. Neurology 70: 1113–1118.
68. de Luca H. Plum L. (2011) Vitamin D deficiency diminishes the severity and delays onsets of experimental autoimmune encephalomyelitis. Arch Biochem Biophys 513: 140–143.
69. Di Pauli F. Reindl M. Ehling R. Schautzer F. Gneiss C. Lutterotti A. et al. (2008) Smoking is a risk factor for early conversion to clinically definite multiple sclerosis. Mult Scler 14: 1026–1030.
70. Disanto G. Chaplin G. Morahan J. Giovannoni G. Hyponnen E. Ramagopalan S. (2012 a) Month of birth, vitamin D and risk of immune mediated disease: a case control study. BMC Med 10: 69.
71. Disanto G. Magalhaes S. Handel A. Morrison K. Sadovnick A. Ebers G. et al. (2011 a) HLA-DRB1 confers increased risk of pediatric-onset MS in children with acquired demyelination. Neurology 76: 781–786.
72. Disanto G. Meier U. Giovannoni G. Ramagopalan S. (2011 b) Vitamin D: a link between Epstein-Barr virus and multiple sclerosis development? Expert Rev Neurother 11: 1221–1224.
73. Disanto G. Morahan J. Ramagopalan S. (2012 b) Multiple sclerosis: risk factors and their interactions. CNS Neurol Disord Drug Targets 11: 545–555.
74. Disanto G. Morahan J. Barnett M. Giovannoni G. Ramagopalan S. (2012 c) The evidence or role of B cells in multiple sclerosis. Neurology 78: 823–832.
75. Disanto G. Pakpoor J. Morahan J. Hall C. Meier U. Giovannoni G. Ramagopalan S. (2012 d) Epstein–Barr virus, latitude and multiple sclerosis. Mult Scler 5 July (Epub ahead of print)
76. Disanto G. Ramagopalan S. Para A. Handunnetthi L. (2011 c) The emerging role of vitamin D binding protein in multiple sclerosis. J Neurol 258: 353–358.
77. Disanto G. Sandve G. Berlanga-Taylor A. Ragnedda G. Morahan J. Watson C. et al. (2012 e) Vitamin D receptor binding, chromatin states and association with multiple sclerosis. Human Mol Genet 21: 3575–3586.
78. Dobson R. Giovannoni G. Ramagopalan S. (2012) The month of birth effect in multiple sclerosis: systematic review, meta-analysis and effect of latitude. J Neurol Neurosurg Psychiatry 18: 1522–1528.
79. Dorr J. Ohlraun S. Skarabis H. Paul F. (2012) Efficacy of vitamin D supplementation in multiple sclerosis (EVIDIMS Trial): study protocol for a randomized trial. Trials 13: 15.
80. Durazo-Arvizu R. Dawson-Hughes B. Sempos C. Yetley E. Looker A. Cao G. et al. (2010) Three-phase model harmonizes estimates of the maximal suppression of parathyroid hormone by 25-hydroxyvitamin D in persons 65 years of age and older. J Nutr 140: 595–599.
81. Dwyer T. van der Mei I. Ponsonby A. Taylo B. Stankovich J. McKay J. et al. (2008) Melanocortin 1 receptor genotype, past environmental sun exposure, and risk of multiple sclerosis. Neurology 71: 583–589.
82. Dyment D. Yee I. Ebers G. Sadovnick A. (2006) Multiple sclerosis in stepsiblings: recurrence risk and ascertainment. J Neurol Neurosurg Psychiatry 77: 258–259.
83. Earthman C. Beckman L. Masodkar K. Sibley S. (2012) The link between obesity and low circulating 25-hydroxyvitamin D concentrations: considerations and implications. Int J Obes 3: 387–396.
84. Ebers G. (2008) Environmental factors and multiple sclerosis. Lancet Neurol 7: 268–277.
85. Ebers G. (2009) Editorial regarding ‘Explaining multiple sclerosis prevalence by ultraviolet exposure: a geospatial analysis’ by Beretich and Beretich. Mult Scler 15: 889–890.
86. Elian M. Nightingale S. Dean G. (1990) Multiple sclerosis among United Kingdom-born children of immigrants from the Indian subcontinent, Africa and the West Indies. J Neurol Neurosurg Psychiatry 53: 906–911.
87. Eyles D. Smith H. Kinobe R. Hewison M. McGrath J. (2005) Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. J Chem Neuroanat 29: 21–30.
88. Fernandes de Abreu D. Babron M. Rebeix I. Fontenille C. Yaouang J. Brassat D. et al. (2009) Season of birth and not vitamin D promoter polymorphisms is a risk factor for multiple sclerosis. Mult Scler 15: 1146–1152.
89. Fernandes de Abreu D. Landel V. Féron F. (2011) Seasonal, gestational and postnatal influences of multiple sclerosis: the beneficial role of vitamin D supplementation in early life. J Neurol Sci 311: 64–68.
90. Fragoso Y. Shearer K. Adoni T. Alves-Leon S. Bidin Brooks J. Comini-Frota E. et al. (2012) Month of birth does not seem to interfere with the development of multiple sclerosis later in life in Brazilian patients. Neuroepidemiology 39: 70–71.
91. Freedman D. Dosemeci M. Alavanja M. (2000) Mortality from multiple sclerosis and exposure to residential and occupational solar radiation: a case-control study based on death certificates. Occup Environ Med 57: 418–421.
92. Gale C. Martyn C. (1995) Migrant studies in multiple sclerosis. Prog Neurobiol 47: 425–448.
93. Garcion E. Wion-Barbot N. Monteiro-Menei C. Berger F. Wion D. (2002) New clues about vitamin d functions in the nervous system. Trends Endocrinol Metab 13: 100–105.
94. Garrett-Mayer E. Wagner C. Hollis B. Kindy M. Gattoni-Celli S. (2012) Vitamin D 3 supplementation (4000 IU / d for 1 y) eliminates differences in circulating 25-hydroxyvitamin D between African American and white men. Am J Clin Nutr 96: 332–336.
95. Gibson J. Summers G. (2011) Bone health in multiple sclerosis. Osteoporos Int 22: 2935–2949.
96. Givon U. Zeilig G. Dolev M. Achiron A. (2012) The month of birth and the incidence of multiple sclerosis in the Israeli population. Neuroepidemiology 38: 64–68.
97. Goldberg P. (1974) Multiple sclerosis: vitamin D and calcium as environmental determinants of prevalence (a view point). Part I: sunlight, dietary factors and epidemiology. Int J Envion Studies 6: 19–27.
98. Goldberg P. Fleming M. Picard E. (1986) Multiple sclerosis: decreased relapse rate through dietary supplementation with calcium, magnesium and vitamin D. Med Hypotheses 21: 193–200.
99. Goodin D. (2009) The causal cascade to multiple sclerosis: a model for pathogenesis. PloS ONE 4: e4565.
100. Grant W. Holick M. (2005) Benefits and requirements of vitamin D for optimal health: a review. Altern Med Rev 10: 94–111.
101. Grau-Lopez L. Granada M. Raich D. Naranjo M. Borras F. Martinez-Caceres E. et al. (2012) Regulatory role of vitamin D in T-cell reactivity against myelin peptides in relapsing-remitting multiple sclerosis patients. BMC Neurol 12: 103.
102. Griffin M. Lutz W. Phan V. Bachman L. McKean D. Kumar R. (2001) Dentritic cell modulation by 1 alpha,25 dihydroxyvitamin D 3 and its analogs: a vitamin D receptor-independent pathway that promotes a persistent state of immaturity in vitro and in vivo. Proc Natl Acad Sci U S A 98: 6800–6805.
103. Haddad J. Chyu K. (1971) Competitive protein-binding radioassay for 25 hydroxycholecalciferol. J Clin Endocrinol Metab 33: 992–995.
104. Haddock L. Corcino J. Vasquez M. (1982) 25(OH)D serum levels in the normal Puerto Rican population and in subjects with tropical sprue and parathyroid disease. Puerto Rico Health Sci J 1: 85–91.
105. Hagenau T. Vest R. Gissel T. Poulsen C. Erlandsem M. Mosekilde L. et al. (2009) Global vitamin D levels in relation to age, gender, skin pigmentation and latitude: an ecologic meta-regression analysis. Osteoporos Int 20: 133–140.
106. Hall L. Kimlin M. Aronov P. Hammock B. Slusser J. Woodhouse L. (2010) Vitamin D intake needed to maintain target serum 25-hydroxyvitamin D concentrations in participants with low sun exposure and dark skin pigmentation is substantially higher than current recommendations. J Nutr 140: 542–550.
107. Hammond S. English D. McLeod J. (2000) The age-range risk of developing multiple sclerosis: evidence from a migrant population in Australia. Brain 123: 968–974.
108. Handel A. Giovannoni G. Ebers G. Ramagopalan S. (2010 a) Environmental factors and their timing in adult-onset multiple sclerosis. Nat Rev Neurol 6: 156–166.
109. Handel A. Williamson A. Disanto G. Dobson R. Giovannoni G. Ramagopalan S. (2011) Smoking and multiple sclerosis: an updated meta-analysis. PloS ONE 6: e16149.
110. Handel A. Williamson A. Disanto G. Handunnetthi L. Giovannoni G. Ramagopalan S. (2010 b) An updated meta-analysis of risk of multiple sclerosis following infectious mononucleosis. PloS ONE 5: e124986.
111. Handunnetthi L. Ramagopalan S. Ebers G. Handunnetthi L. Ramagopalan S. Ebers G. (2010) Multiple sclerosis, vitamin D, and HLA-DRB1*15. Neurology 74: 1905–1910.
112. Hanwell H. Banwell B. (2011) Assessment of evidence for a protective role of vitamin D in multiple sclerosis. Biochim Biophys Acta 1812: 202–212.
113. Hart P. Gorman S. Finley-Jones J. (2011) Modulation of the immune system by UV radiation: more than just the effects of vitamin D? Nat Rev Immunol 11: 584–596.
114. Harvey L. Burne T. McGrath J. Eyles D. (2010) Developmental vitamin D 3 deficiency induces alterations in immune organ morphology and function in adult offspring. J Steroid Biochem Mol Biol 121: 239–242.
115. Hathcock J. Shao A. Vieth R. Heaney R. (2007) Risk assessment for vitamin D. Am J Clin Nutr 85: 6–18.
116. Hayes C. (2000) Vitamin D: a natural inhibitor of multiple sclerosis. Proc Nutr Soc 59: 531–535.
117. Hayes C. Donald Acheson E. (2008) A unifying multiple sclerosis aetiology linking virus infection, sunlight, and vitamin D, through viral interleukin-10. Med Hypotheses 71: 85–90.
118. Healy B. Ali E. Guttmann C. Chitnis T. Glanz B. Buckle G. et al. (2009) Smoking and disease progression in multiple sclerosis. Arch Neurol 66: 858–864.
119. Heaney R. (2000) Vitamin D: how much do we need and how much is too much? Osteoporos Int 11: 553–555.
120. Heaney R. Davies K. Chen T. Holick M. Bager-Lux J. (2003 a) Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr 77: 204–210.
121. Heaney R. Dowell M. Hale C. Bendich A. (2003 b) Calcium absorption varies within the reference range for serum 25-hydroxy vitamin D. J Am Coll Nutr 22: 142–146.
122. Heaney R. Holick M. (2011) Why the IOM recommendations for vitamin D are deficient. J Bone Min Res 26: 455–457.
123. Heaney R. Horst R. Cullen D. Armas L. (2009) Vitamin D 3 distribution and status in the body. J Am Coll Nutr 28: 252–256.
124. Hedström A. Bäärnhielm M. Olsson T. Alfredsson L. (2009) Tobacco smoking, but not Swedish snuff use, increases the risk of multiple sclerosis. Neurology 73: 696–701.
125. Hedström A. Bäärnhielm M. Olsson T. Alfredsson L. (2011 a) Exposure to environmental tobacco smoke is associated with increased risk for multiple sclerosis. Mult Scler 17: 788–793.
126. Hedström A. Olsson T. Alfredsson L. (2012) High body mass index before age 20 is associated with increased risk for multiple sclerosis in both men and women. Mult Scler 18: 1334–1336.
127. Hedström A. Sundqvist E. Bäärnhielm M. Nordin N. Hillert J. Kockum I. et al. (2011 b) Smoking and two human leukocyte antigen genes interact to increase the risk for multiple sclerosis. Brain 134: 653–664.
128. Heine G. Niesner U. Chang D. Steimeyer A. Zügel U. Zuberbier T. et al. (2008) 1,25-dihydroxyvitamin D (3) promotes IL-10 production in human B cells. Eur J Immunol 38: 2210–2218.
129. Hensiek A. Sawcer S. Feakes R. Deans J. Mander A. Akesson E. et al. (2002) HLA-DR 15 is associated with female sex and younger age at diagnosis in multiple sclerosis. J Neurol Neurosurg Neuropsychiatry 72: 184–187.
130. Hernan M. Olek M. Ascherio A. (2001) Cigarette smoking and incidence of multiple sclerosis. Am J Epidemiol 154: 69–74.
131. Hernan M. Jick S. Logroscino G. Olek M. Ascherio A. Jick H. (2005) Cigarette smoking and the progression of multiple sclerosis. Brain 128: 1461–1465.
132. Hewison M. (2012) An update on vitamin D and human immunity. Clin Endocrinol 76: 315–325.
133. Hiremath G. Cettomai D. Baynes M. Ratchord 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. Mult Scler 15: 735–740.
134. Holick M. (2004) Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am J Clin Nutr 80(Suppl.): 1678S–1688S.
135. Holick M. (2007) Vitamin D deficiency. N Engl J Med 357: 266–281.
136. Holick M. (2011) Vitamin D: evolutionary, physiological and health perspectives. Curr Drug Targets 12: 4–18.
137. Holick M. (2012) Vitamin D: extraskeletal health. Rheum Dis Clin North Am 38: 141–160.
138. Holick M. Binkley N. Bischoff-Ferrari H. Gordon C. Hanley D. Heaney R. et al. (2011) Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96: 1911–1930.
139. Holick M. Chen T. Lu Z. Sauter E. (2007) Vitamin D and skin physiology. J Bone Mineral Res 2(Suppl. 2): V28–V33.
140. Hollis B. (2005) Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D. J Nutr 135: 317–322.
141. Holmes V. Barnes M. Alexander H. McFaul P. Wallace J. (2009) Vitamin D deficiency and insufficiency in pregnant women: a longitudinal study. Br J Nutr 102: 876–881.
142. Holmøy T. (2008) Vitamin D status modulates the immune response to Epstein–Barr virus: synergistic effect of risk factors in multiple sclerosis. Med Hypotheses 70: 66–69.
143. Holmøy T. Kampman M. Smolders J. (2012) Vitamin D in multiple sclerosis: implications for assessment and treatment. Exp Rev Neurother 12: 1101–1112.
144. Huang J. Xie Z. (2012) Polymorphisms in the vitamin D receptor gene and multiple sclerosis risk. A meta-analysis of case control studies. J Neurol Sci 313: 79–85.
145. Hypponen E. Power C. (2007) Hypovitaminosis D in British adults at age 45 y: nationwide cohort study of dietary and lifestyle predictors. Am J Clin Nutr 85: 860–868.
146. Ikeda U. Wakita D. Ohkuri T. Chamato K. Kitamura H. Iwakura Y. et al. (2010) 1alpha,25-Dihydroxyvitamin D (3) and all-transretinoic acid synergistically inhibit the differentiation and expression of Th 17 cells. Immunol Lett 134: 7–16.
147. Irizar H. Munoz-Culla M. Zuriarran O. Goyenechea E. Castillo-Trivino T. Prada A. et al. (2012) HLA-DRB1*15:01 and multiple sclerosis: a female association? Mult Scler 18: 569–577.
148. Islam T. Gauderman W. Cozen W. Mack T. (2007) Childhood sun exposure influences risk of multiple sclerosis in monozygotic twins. Neurology 69: 381–388.
149. Jeffery L. Burke F. Mura M. Zheng Y. Quershi O. Hewison M. et al. (2009) 1,25-Dihydroxyvitamin D 3 and IL-2 combine to inhibit T cell production of inflammatory cytokines and promote development of regulatory cells expressing CTLA-4 and FoxP3. J Immunol 183: 5458–5467.
150. Jilek S. Schluep M. Harari A. Canales M. Lysandropoulos A. Zekeridou A. et al. (2012) HLA-B7-restricted EBV-specific CD8+ T cells are dysregulated in multiple sclerosis. J Immunol 188: 4671–4680.
151. Joshi S. Pantalena L. Liu X. Gaffen S. Liu H. Rohowsky-Cochan C. et al. (2011) 1,25-Dihydoxryvitamin B (3) ameliorates Th 17 autoimmunity via transcriptional modulation of interleukin-17A. Mol Cell Biol 31: 3653–3669.
152. Kampman M. Brustad M. (2008) Vitamin D: a candidate for the environmental effect in multiple sclerosis – observations from Norway. Neuroepidemiology 30: 140–146.
153. Kampman M. Steffensen L. Mellgren S. Jørgensen L. (2012) Effect of vitamin D 3 supplementation on relapses, disease progression and measures of function in persons with multiple sclerosis: exploratory outcomes from a double-blind randomised controlled trial. Mult Scler 18: 1144–1151.
154. 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: 471–477.
155. Khoo A. Koenen H. Chai L. Sweep F. Netea M. van der Ven A. Joosten I. (2012) Seasonal variation in vitamin D 3 levels is paralleled by changes in the peripheral human blood cell compartment. PlosOne 7: e29250.
156. Kickler K. Ni Choileain S. Williams A. Richards A. Astier A. (2012) Calcitriol modulates the CD46 pathway in T cells. PloS ONE 7: e48486.
157. Kim M. Kondo T. Takada I. Youn M. Yamamoto Y. Takahashi S. et al. (2009) DNA demethylation in hormone-induced transcriptional derepression. Nature 461: 1007–1012.
158. Kimball S. Burton J. O'Connor P. Vieth R. (2011 a) Urinary calcium response to high dose vitamin D 3 with calcium supplementation in patients with multiple sclerosis. Clin Biochem 44: 930–932.
159. Kimball S. Vieth R. Dosch H. Ber-Or A. Cheung R. Gagne D. et al. (2011 b) Cholecalciferol plus calcium suppresses abnormal PBMC reactivity in patients with multiple sclerosis. J Clin Endocrinol Met 96: 2826–2834.
160. Kirbas A. Kirbas S. Anlar O. Turkyilmaz A. Cure M. Efe H. (2012) Investigation of the relationship between vitamin D and bone mineral density in newly diagnosed multiple sclerosis. Acta Neurol Belg 16 August (Epub ahead of print).
161. Knippenberg S. Bol Y. Damoiseaux J. Hupperts R. Smolders J. (2010) Vitamin D status in patients with MS is negatively correlated with depression but not with fatigue. Acta Neurol Scand 124: 171–175.
162. Knippenberg S. Smolders J. Thewissen M. Peelen E. Terwaert J. Hupperts R. et al. (2011) Effect of vitamin D (3) supplementation on peripheral B cell differentiation and isotype switching in patients with multiple sclerosis. Mult Scler 17: 1418–1423.
163. Koch M. Metz L. Kovalchuk O. (2012) Epigenetic changes in patients with multiple sclerosis. Nat Rev Neurol 9: 35–43.
164. Koch M. van Harten A. Uyttenboogaart M. de Keyser J. (2007) Cigarette smoking and progression in multiple sclerosis. Neurology 69: 1515–1520.
165. Kragt J. van Amerongen B. Killestein J. Dijkstra C. Uitdehaag B. Polman C. et al. (2009) Higher levels of 25-hydroxyvitamin D are associated with a lower incidence of multiple sclerosis only in women. Mult Scler 15: 9–15.
166. Kurtzke J. (1967) On the fine structure of the distribution of multiple sclerosis. Acta Neurol Scan 43: 257–282.
167. Kurtzke J. (1995) MS epidemiology world wide. One view of current status. Acta Neurol Scand 161(Suppl.): 23–33.
168. Kurtzke J. (2008) Some contributions of the Department of Veterans Affairs to the epidemiology of multiple sclerosis. Mult Scler 14: 1007–1012.
169. Kurtzke J. Beebe J. Norman J. (1985) Epidemiology of multiple sclerosis in US veterans: III. Migration and the risk of MS. Neurology 35: 672–678.
170. Lassmann H. Niedobitek G. Aloisi F. Middeldorp J. and the NeuroproMiSe EBV Working Group (2010) Epstein–Barr virus in the multiple sclerosis brain: a controversial issue-report on a focused workshop held in the Centre for Brain Research of the Medical University of Vienna, Austria. Brain 134: 2772–2786.
171. Lemire J. Adams J. Sakai R. Jordan S. (1984) 1 alpha,25-dihydroxyvitamin D 3 suppresses proliferation and immunoglobulin production by normal human peripheral blood mononuclear cells. Clin Invest 74: 657–661.
172. Lemire J. Archer D. (1991) 1,25-Dihydroxyvitamin D 3 prevents the in vivo induction of murine experimental autoimmune encephalomyelitis. J Clin Ivest 87: 1103–1107.
173. Lemire J. Archer D. Beck L. Spiegelberg H. (1995) Immunosuppressive actions of 1,25-dihydroxyvitamin D3: preferential inhibition of Th 1 functions. J Nutr 125: 1704S–1708S.
174. Leu M. Giovannucci E. (2011) Vitamin D: epidemiology of cardiovascular risks and events. Best Pract Res Clin Endocrinol Met 25: 633–646.
175. Levin L. Munger K. O'Reilly E. Falk K. Ascherio A. (2010) Primary infection with the Epstein-Barr virus and risk of multiple sclerosis. Ann Neurol 67: 824–830.
176. Levin L. Munger K. Rubertone M. Peck C. Lenette E. Spiegeman D. et al. (2005) Temporal relationship between elevation of Epstein-Barr virus antibody titers and initial onset of neurological symptoms in multiple sclerosis. JAMA 293: 2496–2500.
177. Lewis S. Lucas R. Halliday J. Ponsonby A. (2010) Vitamin D deficiency and pregnancy: from preconception to birth. Mol Nutr Food Res 54: 1092–1102.
178. Lin R. Charlesworth J. van der Mei I. Taylor B. (2012) The genetics of multiple sclerosis. Pract Neurol 12: 279–288.
179. Lindsey J. Khan U. Ansari W. Powell T. Wang Y. Guirguis M. (2012) The antibody response to Epstein–Barr virions is altered in multiple sclerosis. J Neuroimmunol 254: 146–153.
180. Lips P. (2006) Vitamin D physiology. Prog Biophys Mol Biol 92: 4-8.
181. Løken-Amsrud K. Holmøy T. Bakke S. Beiske A. Bjerve K. Bjørnarå B. et al. (2012) Vitamin D and disease activity in multiple sclerosis before and during interferon-β treatment. Neurology 79: 267–273.
182. Lonergan R. Kinsella K. Fitzpatrick P. Brady J. Murray B. Dunne C. et al. (2011) Multiple sclerosis prevalence in Ireland: relationship to vitamin D status and HLA genotype. J Neurol Neorosurg Psychiatry 82: 317–322.
183. Lossius A. Vartdal S. Holmøy T. (2011) Vitamin D sensitive EBNA-1 specific T cells in the cerebrospinal fluid of patients with multiple sclerosis. J Immunol 240-241: 85–96.
184. Lucas R. Ponsonby A. Dear K. Valery P. Pender M. Burrows J. et al. (2011 a) Current and past Epstein–Barr virus infection in risk of initial CNS demyelination. Neurology 77: 371–379.
185. Lucas R. Ponsonby A. Dear K. Valery P. Pender M. Taylor B. et al. (2011 b) Sun exposure and vitamin D are independent risk factors for CNS demyelination. Neurology 76: 540–548.
186. Lünemann J. Tintoré M. Messmer B. Strowiq T. Rovira A. Perkal H. et al. (2010) Elevated Epstein–Barr virus-encoded nuclear antigen-1 immune responses predict conversion to multiple sclerosis. Ann Neurol 57: 159–169.
187. Luxwolda M. Kuiperst R. Kema I. Dijck-Brouwer J. Muskiet F. (2012) Traditionally living populations in East Africa have a mean serum 25-hydroxyvitamin D concentration of 115 nmol/L. Br J Nutr 108: 1557-1561.
188. Lysandropoulos A. Jaquiéry E. Jilek S. Pantealo G. Schluep M. Du Pasquier R. (2011) Vitamin D has a direct immunomodulatory effect on CD8+ T cells of patients with early multiple sclerosis and in healthy controls. J Neuroimmunol 233: 240–244.
189. Ma Y. Zhang P. Wang F. Yang J. Liu Z. Qin H. (2011) Association between vitamin D and risk of colorectal cancer: a systematic review of prospective studies. J Clin Oncol 29: 3775–3782.
190. 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: 128–132.
191. Mameli G. Poddighe L. Mei A. Uleri E. Sotgiu S. Serra C. et al. (2012) Expression and activation by Epstein Barr virus of human endogenous retroviruses in blood cells and astrocytes: inference for multiple sclerosis. PloS ONE 7: e44991.
192. Marrie R. Cutter G. Tyry T. Vollmer T. (2009) A cross-sectional study of bone health in multiple sclerosis. Neurology 73: 1394–1398.
193. Mattner F. Smiroldo S. Gabliati F. Muller M. Di Lucia P. Poliani P. et al. (2000) Inhibition of Th 1 development and treatment of chronic-relapsing experimental allergic encephalomyelitis by a non-hypercalcemic analogue of 1,25-dihydroxyvitamin D3. Eur J Neuroimmunol 30: 498–508.
194. Mayne C. Spanier J. Relland L. Williams C. Hayes C. (2011) 1,25-Dihydroxyvitamin D 3 acts directly on the T lymphocyte vitamin D receptor to inhibit experimental autoimmune encephalomyelitis. Eur J Immunol 41: 822–832.
195. McDowell T. Amr S. Culpepper W. Langenberg P. Royal W. Bever C. et al. (2011) Sun exposure, vitamin D and age at disease onset in relapsing multiple sclerosis. Neuroepidemiology 36: 39–45.
196. McDowell T. Amr S. Langenberg B. Royal W. Bever C. Culpepper W. et al. (2010) Time of birth, residential solar radiation and age at onset of multiple sclerosis. Neuroepidemiology 34: 238–244.
197. McLeod J. Hammond S. Kurtzke J. (2011) Migration and multiple sclerosis in immigrants to Australia from United Kingdom and Ireland: a reassessment. I. Risk of MS by age at immigration. J Neurol 258: 1140–1149.
198. Mehan T. de Luca H. (2002) The vitamin D receptor is essential for 1alpha,25-dihydroxyvitamin D (3) to suppress experimental autoimmune encephalomyelitis in mice. Arch Biochem Biophys 408: 200–204.
199. Mikaeloff Y. Caridade G. Tardieu M. Suissa S. and the KIDSEP Study Group (2007) Parental smoking at home and the risk of childhood-onset multiple sclerosis in children. Brain 130: 2589–2595.
200. Mirzaei F. Michels K. Munger K. O'Reilly E. Chitnis T. Forman M. et al. (2011) Gestational vitamin D and the risk of multiple sclerosis in offspring. Ann Neurol 70: 30–40.
201. Moen S. Celius E. Sandvik L. Brustad M. Nordsletten L. Eriksen E. et al. (2012) Bone turnover and metabolism in patients with early multiple sclerosis and prevalent bone mass deficit. A population-based case-control study. PloS ONE 7: e45703.
202. Moen S. Celius E. Sandvik L. Nordsletten L. Eriksen E. Holmøy T. (2011) Low bone mass in newly diagnosed multiple sclerosis and clinically isolated syndrome. Neurology 77: 151–157.
203. Montgomery S. Bahmanyar S. Hillert J. Ekbom A. Olsson T. (2008) Maternal smoking during pregnancy and multiple sclerosis amongst offspring. Eur J Neurol 15: 1395–1399.
204. Moore C. Murphy M. Holick M. (2005) Vitamin D intakes by children and adults in the United States differ among ethnic groups. J Nutr 135: 2478–2485.
205. Morgan J. Morgan D. Lasky S. Ford D. Kouttab N. Maizel A. (1996) Requirements for induction of vitamin D-mediated gene regulation in normal human B lymphocytes. J Immunol 157: 2900–2908.
206. Morris H. Anderson P. (2010) Autocrine and paracrine actions of vitamin d. Clin Biochem Rev 31: 129–138.
207. Mosayebi G. Ghazavi A. Ghasami K. Kokhaei P. (2011) Therapeutic effect of vitamin D 3 in multiple sclerosis patients. Immunol Invest 40: 627–639.
208. Mowry E. (2011) Vitamin D: evidence for its role as a prognostic factor in multiple sclerosis. J Neurol Sci 311: 19–22.
209. 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 MS. Ann Neurol 67: 618–624.
210. Mowry E. Waubant E. McCulloch C. Okuda D. Evangelista A. Lincoln R. et al. (2012) Vitamin D status predicts new brain magnetic resonance imaging activity in multiple sclerosis. Ann Neurol 72: 234–240.
211. Müller K. Odum N. Bendizen K. (1993) 1,25-Dihydroxyvitamin D 3 selectively reduces interleukin-2 levels and proliferation of human T cell lines in vitro. Immunol Lett 35: 177–182.
212. Munger K. Ascherio A. (2011) Prevention and treatment of MS: studying the effects of vitamin D. Mult Scler 17: 1405–1411.
213. Munger K. Chitnis T. Ascherio A. (2009) Body size and risk of MS in two cohorts of US women. Neurology 73: 1543–1550.
214. Munger K. Chitnis T. Frazier A. Giovannucci E. Spiegelman D. Ascherio A. (2011 a) Dietary intake of vitamin D during adolescence and risk of multiple sclerosis. J Neurol 258: 479–485.
215. Munger K. Levin L. Hollis B. Howard N. Ascherio A. (2006) Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 296: 2832–2838.
216. Munger K. Levin R. O'Reilly E. Falk K. Ascherio A. (2011 b) Anti-Epstein Barr virus antibodies as serological markers of multiple sclerosis: a prospective study among United States military personal. Mult Scler 17: 1185–1193.
217. Munger K. Zhang S. O'Reilly E. Hernan M. Olek M. Willet W. et al. (2004) Vitamin D intake and incidence of multiple sclerosis. Neurology 62: 60–65.
218. Muthian G. Raikvar H. Rajasingh J. Brigh J. (2006) 1,25-Dihydroxyvitamin D 3 modulates JAK STAT pathway in IL-12/IFNgamma axis leading to Th 1 response in experimental allergic encephalomyelitis. J Neurosci Res 83: 1299–1309.
219. Myrh K. (2009) Vitamin D treatment in multiple sclerosis. J Neurol Sci 286: 104–108.
220. Nashold F. Miller D. Hayes D. (2000) 1,25-Dihydroxyvitamin D 3 treatment decreases macrophage accumulation of mice with experimental autoimmune encephalomyelitis. J Neuroimmunol 103: 171–179.
221. Nashold F. Spach K. Spanier J. Hayes C. (2009) Estrogen controls vitamin D3-mediated resistance to experimental autoimmune encephalomyelitis by controlling vitamin D 3 metabolism and receptor expression. J Immunol 183: 3672–3681.
222. Neau J. Artaud-Uriot M. Lhomme V. Bounaud J. Lebras F. Boissonnot L. et al. (2011) Vitamin D and multiple sclerosis. A prospective survey of patients of Poitou-Charentes area. Rev Neurol 167: 317–323.
223. Nielsen T. Pedersen M. Rostgaard K. Frisch M. Hjalgrim H. (2007 a) Correlations between Epstein–Barr virus antibody levels and risk factors for multiple sclerosis in healthy individuals. Mult Scler 13: 420–423.
224. Nielsen T. Rostgaard K. Askling J. Steffensen R. Oturai A. Jersild C. et al. (2009) Effects of infectious mononucleosis and HLA-DRB1*15 in multiple sclerosis. Mult Scler 15: 431–436.
225. Nielsen T. Rostgaard K. Nielsen N. Koch-Henriksen N. Haarh S. Sørensen P. et al. (2007 b) Multiple sclerosis after infectious mononucleosis. Arch Neurol 64: 72–75.
226. 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: 1687–1694.
227. Niino M. Fukazawa T. Kikuchi S. Sasaki H. (2008) Therapeutic potential of vitamin D for multiple sclerosis. Cur Med Chem 15: 499–505.
228. Niino M. Fukazawa T. Yabe I. Kikuchi S. Sasaki H. Tashiro K. (2000) Vitamin D receptor gene polymorphism in multiple sclerosis and the association with HLA class II alleles. J Neurol Sci 177: 65–71.
229. Niller N. Wolf H. Minarovits J. (2008) Regulation and dysregulation of Epstein–Barr virus latency: implications for the development of autoimmune diseases. Autoimmunity 41: 298–328
230. Nolan D. Castley A. Tschoschner M. James I. Qiu W. Sayer D. et al. (2012) Contributions of vitamin D elements and HLA promoters to multiple sclerosis risk. Neurology 79: 538–546.
231. Norman A. Bouillon R. (2010) Vitamin D nutritional policy needs a vision for the future. Exp Biol Med 235: 1034–1045.
232. Novakovic B. Sibson N. Ng A. Manuelpillai U. Rakyan V. Down T. et al. (2009) Placenta-specific methylation of the vitamin D 24-hydroxylase gene: implications for feedback autoregulation of vitamin D levels at the fetomaternal interface. J Biol Chem 284: 14838–14848.
233. O'Donnell S. Cranney A. Horsley T. Weiler H. Atkinson S. Hanley D. et al. (2008) Efficacy of food fortification on serum 25-hydroxyvitamin D concentrations: systematic review. Am J Clin Nutr 88: 1528–1534.
234. Okazaki R. Sugimoto T. Kaji H. Fujii Y. Shiraki M. Inoue D. et al. (2011) Vitamin D insufficiency defined by serum 25-hydroxyvitamin D and parathyroid hormone before and after oral vitamin D 3 supplementation load in Japanese patients. J Bone Miner Metab 29: 103–110.
235. Orton S. Ramagopalan S. Para A. Lincoln M. Handunnetthi L. Chao M. et al. (2011 a) Vitamin D metabolic pathway genes and risk of multiple sclerosis in Canadians. J Neurol Sci 305: 116–120.
236. Orton S. Wald L. Confavreux C. Vukusic S. Krohn J. Ramagopalan S. et al. (2011 b) Association of UV radiation with multiple sclerosis prevalence and sex ratio in France. Neurology 76: 425–431.
237. Owens G. Bennett J. (2012) Trigger, pathogen or bystander: the complex nexus linking Epstein-Barr virus and multiple sclerosis. Mult Scler 18: 1204–1208.
238. Ozgocmen S. Bulut S. IIhan N. Gulkesen A. Ardicoglu O. Ozkan Y. (2005) Vitamin D deficiency and reduced bone mineral density in multiple sclerosis: effect of ambulatory status and functional capacity. J Bone Miner Metab 23: 309–313.
239. Pakpoor J. Disanto G. Gerber J. Dobson R. Meier U. Giovannoni G. et al. (2012) The risk of developing multiple sclerosis in individuals negative for Epstein–Barr virus: a meta-analysis. Mult Scler 11 June (Epub ahead of print).
240. Pedersen L. Nashold F. Spach K. Hayes C. (2007) 1,25 Dihydroxyvitamin D 3 reverses experimental autoimmune encephalomyelitis by inhibiting chemokines synthesis and monocyte trafficking. J Neurosci Res 85: 2480–2490.
241. Peferoen L. Lamers F. Lodder L. Gerritsen W. Huitinga I. Melief J. et al. (2010) Epstein Barr virus is not a characteristic feature in the central nervous system in established multiple sclerosis. Brain 133: 1–4.
242. Pekmezovic T. Drulovic J. Milenkovic M. Jarebinski M. Stojsavljevic N. Mesaros S. et al. (2006) Lifestyle factors and multiple sclerosis: a case-control study in Belgrade. Neuroepidemiology 27: 212–216.
243. Perron H. Germi R. Bernard C. Garcia-Montojo M. Deluen C. Farinelli L. et al. (2012) Human endogenous retrovirus type W envelope expression in blood and brain cells provides new insights into multiple sclerosis disease. Mult Scler 18: 1721-1736.
244. Pierrot-Deseilligny C. (2009) Clinical implications of a possible role of vitamin D in multiple sclerosis. J Neurol 256: 1468–1479.
245. Pierrot-Deseilligny C. Rivaud-Péchoux S. Clerson P. de Paz R. Souberbielle J. (2012) Relationship between 25-OH-D serum level and relapse rate in multiple sclerosis patients before and after vitamin D supplementation. Ther Adv Neurol Disord 5: 187–198.
246. Pierrot-Deseilligny C. Souberbielle J. (2010) Is hypovitaminosis D one of the environmental risk factors for multiple sclerosis? Brain 133: 1869–1888.
247. Pierrot-Deseilligny C. Souberbielle J. (2011) Widespread vitamin D insufficiency: a new challenge for primary prevention with particular reference to multiple sclerosis. Presse Médicale 40: 349–356.
248. Pike J. Meyer M. (2010) The vitamin D receptor: new paradigms for the regulation of gene expression by 1,25-dihydroxyvitamin D (3). Endocrinol Metab Clin North Am 39: 255–269.
249. Pittas F. Ponsonby A. van der Mei I. Taylor B. Blizzard L. Groom P. et al. (2009) Smoking is associated with progressive disease course and increased progression in clinical disability in a prospective cohort of people with multiple sclerosis. J Neurol 256: 577–585.
250. Priemel M. von Doramus C. Klatte T. Kessler S. Schlie J. Meier S. et al. (2010) Bone mineralization defects and vitamin D deficiency: histomorphometric analysis of iliac crest bone biopsies and circulating 25-hydroxyvitamin D in 675 patients. J Bone Miner Res 25: 305–312.
251. Prietl B. Pilz S. Wolf M. Tomaschitz A. Obermayer-Pietsch B. Graninger W. et al. (2010). Vitamin D supplementation and regulatory T cells in apparently healthy subjects: vitamin D treatment for autoimmune diseases? IMAJ 12: 136–139.
252. Prosser D. Jones G. (2004) Enzymes involved in the activation and inactivation of vitamin D. Trends Biochem Sci 29: 664–673.
253. Provvedini D. Tsoukas C. Deftos L. Manolagas S. (1983) 1,25-Dihydroxyvitamin D 3 receptors in human leukocytes. Science 221: 1181–1183.
254. Pugliatti M. Rosati G. Carton H. Riise T. Drulovic J. Vécsei L. et al. (2006) The epidemiology of multiple sclerosis in Europe. Eur J Neurol 13: 700–722.
255. Ramagopalan S. Dyment D. Cader M. Morrison K. Disanto G. Morahan J. et al. (2011 a) Rare variants in the CYP27B1 gene are associated with multiple sclerosis. Ann Neurol 70: 881–886.
256. Ramagopalan S. Handel A. Giovannoni G. Rutherford Siegel S. Ebers G. Chaplin G. (2011 b) Relationship of UV exposure to prevalence of multiple sclerosis in England. Neurology 76: 1410–1414.
257. Ramagopalan S. Link J. Byrnes J. Dyment D. Giovannoni G. Hintzen R. et al. (2009 a) HLA-DRB1 and month of birth in multiple sclerosis. Neurology 73: 2107–2111.
258. Ramagopalan S. Maugeri N. Handunnetthi I. Lincoln M. Orton S. Dyment D. et al. (2009 b) Expression of the multiple sclerosis-associated MHC class II Allele HLA-DRB1*1501 is regulated by vitamin D. PLoS Genet 5: e1000369.
259. Ramagopalan S. Valdar W. Dyment D. de Luca G. Yee I. Giovannoni G. et al. (2009 c) Association of infectious mononucleosis with multiple sclerosis. A population-based study. Neuroepidemiology 32: 257–262.
260. Reichel H. Koeffler H. Tobler A. Norman A. (1987) 1 alpha,25-Dihyroxyvitamin D 3 inhibits gamma-interferon synthesis by normal human peripheral blood lymphocytes. Proc Natl Acad Sci U S A 84: 3385–3389.
261. Rigby W. Waugh M. Graziano R. (1990) Regulation of human monocyte HLA-DR and CD4 antigen expression, and antigen presentation of 1,25-dihydroxyvitamin D3. Blood 76: 189–197.
262. Riise T. Nortvedt M. Ascherio A. (2003) Smoking is a risk factor for multiple sclerosis. Neurology 61: 1122–1124.
263. Ross A. Manson E. Abrams S. Aloia J. Brannon P. Steven K. 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: 53–58.
264. Royal W. 3rd Mia Y. Li H. Nauton K. (2009) Peripheral blood regulatory T cell measurements correlate with serum vitamin D levels in patients with multiple sclerosis. J Neuroimmunol 213: 135–141.
265. Runia T. Hop W. de Rijke Y. Buljevac D. Hintzen R. (2012) Lower serum vitamin D levels are associated with a higher relapse risk in multiple sclerosis. Neurology 79: 261–266.
266. Saastamoinen K. Auvinen M. Tienari P. (2012) Month of birth is associated with multiple sclerosis but not with HLA-DR15 in Finland. Mult Scler 18: 563–568.
267. Šaltytė Benth J. Myhr K. Løken-Amsrud K. Beiske A. Bjerve K. Hovdal H. et al. (2012) Modelling and prediction of 25-hydroxyvitamin D levels in Norwegian relapsing-remitting multiple sclerosis patients. Neuroepidemiology 39: 84–93.
268. Salzer J. Hallmans G. Nyström M. Stenlund H. Wadell G. Sundström P. (2012 a) Vitamin D as a protective factor in multiple sclerosis. Neurology 79: 2140–2145.
269. Salzer J. Nyström M. Hallmans G. Stenlund H. Wadell G. Sundström P. (2012 b) Epstein–Barr virus and vitamin D as risk factors for multiple sclerosis. Mult Scler 18(Suppl. 4): 373-374.
270. Salzer J. Svenningsson A. Sundström P. (2010) Season of birth and multiple sclerosis in Sweden. Acta Neurol Scand 121: 20–23.
271. Sargsyan S. Shearer A. Ritchie A. Burgoon M. Anderson S. Hemmer B. et al. (2010) Absence of Epstein–Barr virus in the brain and CSF of patients with multiple sclerosis. Neurology 74: 1127–1135.
272. Sawcer S. Hellenthai G. Pirinen M. Spencer C. Patsopoulos N. Moutsanias L. et al. The International Multiple Sclerosis Genetics Consortium and Wellcome Trust Case Control Consortium 2 (2011) Genetic risk and primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 476: 214–219.
273. Schlingmann K. Kaufman M. Weber S. Inwin A. Goos C. John U. et al. (2011) Mutations in CYP24A1 and idiopathic infantile hypercalcemia. N Engl J Med 365: 410-421.
274. Schmidt H. Williamson D. Ashley-Koch A. (2007) HLA-DR15 haplotype and multiple sclerosis: a HuGE review. Am J Epidemiol 165: 1097–1109.
275. Schwalfenberg G. Genuis S. Hiltz M. (2010) Addressing vitamin D deficiency in Canada: a public health innovation whose time has come. Public Health 124: 350–359.
276. Serafini B. Rosicarelli B. Franciotta D. Magliozzi R. Reynolds R. Cinque P. et al. (2007) Dysregulated Epstein–Barr virus infection in the multiple sclerosis brain. J Exp Med 204: 2899–2912.
277. Serafini B. Severa M. Columba-Cabezas S. Rosicarelli B. Veroni C. Chiappetta G. et al. (2010) Epstein–Barr virus latent infection and BAFF expression in B cells in the multiple sclerosis brain: implications for viral persistence and intrathecal B-cell activation. J Neuropathol Exp Neurol 69: 677–693.
278. Shaygannejad V. Janghorbani M. Ashtari F. Dehghan H. (2012) Effect of adjunct low-dose vitamin D on relapsing remitting multiple sclerosis progression: preliminary findings of a randomized placebo-controlled study. Mult Scler Int 2012: 452541.
279. Sigmundsdottir H. Pan J. Debes J. Alt C. Habtezion A. Soler D. et al. (2007) DCs metabolize sunlight-induced vitamin D 3 to ‘program’ T cell attraction to the epidermal chemokine CCL27. Nat Immunol 8: 285–293.
280. Silva K. Alvarenga R. Fernandez Y. Alvarenga H. Thuler L. (2009) Potential risk factors for multiple sclerosis in Rio de Janeiro: a case-control study. Arq Neuropsiquiatr 67: 229–234.
281. Simon K. Munger K. Ascherio A. (2012 a) Vitamin D and multiple sclerosis: epidemiology, immunology and genetics. Curr Opin Neurol 25: 246–251.
282. Simon K. Munger K. Kraft P. Hunter D. de Jager P. Ascherio A. (2011) Genetic predictors of 25-hydroxyvitamin D levels and risk of multiple sclerosis. J Neurol 258: 1676–1682.
283. Simon K. O'Reilly E. Munger K. Finerty S. Morgan A. Ascherio A. (2012 b) Epstein–Barr virus neutralizing antibody levels and risk of multiple sclerosis. Mult Scler 18: 1185–1187.
284. Simon K. van der Mei I. Munger K. Ponsonby A. Dickinson J. Dwyer T. et al. (2010) Combined effects of smoking, anti-EBNA antibodies and HLA-DBR1*1501 on multiple sclerosis risk. Neurology 74: 1365–1411.
285. Simpson S. Jr Blizzard L. Otahal P. van der Mei I. Taylor B. (2011) Latitude is significantly associated with the prevalence of multiple sclerosis: a meta-analysis. J Neurol Neurosurg Psychiatry 82: 1132–1141.
286. Simpson S. Taylor B. Blizzard L. Ponsonby A. Pittas F. Tremlett H. et al. (2010) Higher 25-hydroxyvitamin D is associated with lower relapse risk in MS. Ann Neurol 68: 193–203.
287. Sioka C. Kyritsis A. Fotopoulos A. (2009) Multiple sclerosis, osteoporosis, and vitamin D. J Neurol Sci 287: 1–6.
288. Sloka J. Pryse-Phillips W. Stefanelli M. (2008) The relation of ultraviolet radiation and multiple sclerosis in Newfoundland. Can J Neurol Sci 35: 69–74.
289. Sloka S. Silva C. Pryse-Phillips W. Patten S. Metz L. Yong V. (2011 a) A quantitative analysis of suspected environmental causes of MS. Can J Neurol Sci 38: 98–105.
290. Sloka S. Silva C. Wang J. Yong V. (2011 b) Predominance of Th 2 polarization by vitamin D through a STAT6-dependent mechanism. J Neuroinflammation 8: 56.
291. Smolders J. Damoiseaux J. Menheree P. Hupperts R. (2008 a) Vitamin D as an immune modulator in multiple sclerosis, a review. J Neuroimmunol 194: 7–17.
292. Smolders J. Hupperts R. Barkhof R. Grimaldi L. Holmoy T. Killestein J. et al. (2011 a) Efficacy of vitamin D (3) as add-on therapy in patients with relapsing-remitting multiple sclerosis receiving subcutaneous interferon beta 1-a: a phase II, multicenter, double-blind, randomized, placebo-controlled trial. J Neurol Sci 311: 44–49.
293. Smolders J. Menheere P. Kessels A. Damoiseaux J. Hupperts R. (2008 b) Association of vitamin D metabolite levels with relapse rate and disability in multiple sclerosis. Mult Scler 14: 1–5.
294. Smolders J. Menheere P. Thewissen M. Peelen E. Tervaert J. Hupperts R. et al. (2010 a) Regulatory T cell function correlates with serum 25-hydroxyvitamin D, but not with 1,25 dihydroxyvitamin D, parathyroid hormone and calcium levels in patients with relapsing remitting multiple sclerosis. J Steroid Biochem Mol Biol 121: 243–246.
295. Smolders J. Moen S. Damoiseaux J. Huitinga I. Holmøy T. (2011 b) Vitamin D in the healthy and inflamed central nervous system: access and function. J Neurol Sci 311: 37–43.
296. Smolders J. Peelen E. Thewissen M. Cohen Tervaet J. Menheere P. Hupperts R. et al. (2010 b) Safety and T cell modulating effects of high dose vitamin D 3 supplementation in multiple sclerosis. PloS ONE 5 (12): e15235.
297. Smolders J. Thewissen M. Peelen E. Menheere P. Tervaert J. Damoiseaux J. et al. (2009) Vitamin D status is positively correlated with regulatory T cell function in patients with multiple sclerosis. PloS ONE 4: e6635.
298. Smolders J. Thewissen M. Theunissen R. Peelen E. Knippenberg S. Menheere P. et al. (2011 c) Vitamin D-related gene expression profiles in immune cells of patients with relapsing remitting multiple sclerosis. J Neuroimmunol 235: 91–97.
299. Soilu-Hänninen M. Airas L. Monnonen I. Heikkilä A. Viljanen N. Hänninen A. (2005) 25 Hydroxyvitamin D levels in serum at the onset of multiple sclerosis. Mult Scler 11: 266–271.
300. Soilu-Hänninen M. Aivo J. Lindström B. Elovaara I. Sumelhati M. Färkkilä M. et al. (2012) A randomised, double blind, placebo controlled trial with vitamin D 3 as an add-on treatment to interferon β-1b in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 83: 565–571.
301. Sokal E. Hoppenbrouwers K. Vandermeulen C. Moutschen S. Léonard P. Moreels A. et al. (2007) Recombinant gp 350 vaccine for infectious mononucleosis: a phase 2, randomized, double-blind, placebo-controlled trial to evaluate the safety, immunogenicity, and efficacy of an Epstein–Barr virus vaccine in healthy young adults. J Infect Dis 196: 1749–1753.
302. Sotgiu S. Pugliatti M. Sotgiu M. Fois M. Arru G. Sanna A. et al. (2006) Seasonal fluctuation of multiple sclerosis births in Sardinia. J Neurol 253: 38–44.
303. Souberbielle J. Body J. Lappe J. Plebani M. Shoenfeld Y. Wang T. et al. (2010) Vitamin D and musculoskeletal health, cardiovascular disease, autoimmunity and cancer: recommendations for clinical practice. Autoimmun Rev 9: 709–715.
304. Spach K. Hayes C. (2005) Vitamin D 3 confers protection from autoimmune encephalomyelitis only in female mice. J Immunol 175: 4119–4126.
305. Spach K. Nashold F. Dittel B. Hayes C. (2006) IL-10 signaling is essential for 1,25 dihydroxyvitamin d3-mediated inhibition of experimental autoimmune encephalomyelitis. J Immunol 177: 6030–6037.
306. Spach K. Pedersen L. Nashold F. Kayo T. Yandell B. Prolla T. et al. (2004) Gene expression analysis suggests that 1,25-dihydroxyvitamin D 3 reverses experimental autoimmune encephalomyelitis by stimulating inflammatory cell apoptosis. Physiol Genomics 18: 141–151.
307. Spanier J. Nashold F. Olson J. Hayes C. (2012) The Ifng gene is essential for VDR gene expression and vitamin D3-mediated reduction of pathogenic T cell burden in the central nervous system in experimental autoimmune encephalomyelitis. J Immunol 189: 3188–3197.
308. Staples J. Ponsonby A. Lim L. (2010) Low maternal exposure to ultraviolet radiation in pregnancy, month of birth, and risk of multiple sclerosis in offspring: longitudinal analysis. BMJ 340: c.
309. Steffensen L. Jørgensen L. Straume B. Mellgren S. Kampman M. (2011) Can vitamin D supplementation prevent bone loss in persons with MS? A placebo-controlled trial. J Neurol 258: 1624–1631.
310. Steffensen L. Mellgren S. Kampman M. (2010) Predictors and prevalence of low bone mineral density in fully ambulatory persons with multiple sclerosis. J Neurol 257: 410–418.
311. Stein M. Liu Y. Gray O. Baker J. Kolbe S. Ditchfield M. et al. (2011) A randomized trial of high-dose vitamin D 2 in relapsing-remitting multiple sclerosis. Neurology 77: 1611–1618.
312. Stewart N. Simpson S. van der Mei I. Ponsonby A. Blizzard L. Dwyer T. et al. (2012) Interferon-β and serum 25-hydroxyvitamin D interact to modulate relapse risk in MS. Neurology 79: 254–260.
313. Subramanian S. Miller L. Grafe M. Vanderbark A. Offner H. (2012) Contribution of GPR 30 for 1,25-dihydroxyvitamin D 3 protection in EAE. Metab Brain Dis 27: 29–35.
314. Sundqvist E. Bäärnhielm M. Alfredsson L. Hillert J. Olsson T. Kockum I. (2010) Confirmation of association between multiple sclerosis and CYP27B1. Eur J Hum Gen 18: 1349–1352.
315. Sundqvist E. Sundström P. Lindén M. Hedström A. Aloisi F. Hillert J. et al. (2012 a) Epstein–Barr virus and multiple sclerosis: interaction with HLA. Genes Immun 13: 14–20.
316. Sundqvist E. Sundström P. Lindén M. Hedström A. Aloisi F. Hillert J. et al. (2012 b) Lack of replication of interaction between EBNA 1 IgG and smoking in risk for multiple sclerosis. Neurology 79: 1363–1368.
317. Sundström P. Juto P. Wadell G. Hallmans G. Svenninggson A. Nyström R. et al. (2004) An altered immune response to Epstein-Barr virus in multiple sclerosis: a prospective study. Neurology 62: 2277–2282.
318. Sundström P. Nyström L. (2008) Smoking worsens the prognosis in multiple sclerosis. Mult Scler 14: 1031–1035.
319. Sundström P. Nyström L. Hallmans G. (2008) Smoke exposure increases the risk for multiple sclerosis. Eur J Neurol 15: 579–583.
320. Sundström P. Nyström R. Ruuth K. Lundgren E. (2009) Antibodies to specific EBNA-1 domains and HLA-DRB1*1501 interact as risk factors for multiple sclerosis. J Neuroimmunol 215: 102–107.
321. Tang J. Zhou R. Luger D. Zhu W. Silver P. Grajewski R. et al. (2009) Calcitriol suppresses antiretinal autoimmunity through inhibitory effects on the Th 17 effector response. J Immunnol 182: 4624–4632.
322. Taylor B. Lucas R. Dear K. Kilpatrick T. Pender M. van der Mei I. et al. (2010) Latitudinal variation in incidence and type of first central nervous system demyelinating events. Mult Scler 16: 398–405.
323. Taylor B. Richardson A. Mason D. Willoughby E. Abenethy D. Sabel C. (2008) Prevalence of multiple sclerosis in New Zealand. Mult Scler 14(Suppl. 1): S202.
324. Templer D. Trent N. Spencer D. Trent A. Corgiat M. Mortensen P. et al. (1992) Season of birth in multiple sclerosis. Acta Neurol Scand 85: 107–109.
325. Thacker E. Mizraei F. Ascherio A. (2006) Infectious mononucleosis and risk of multiple sclerosis: a meta-analysis. Ann Neurol 59: 499–503.
326. Torkildsen Ø. Knappskog P. Nyland H. Myhr K. (2008) Vitamin D-dependent rickets as a possible risk factor for multiple sclerosis. Arch Neurol 65: 809–811.
327. Torskilden Ø. Stansberg C. Anglelskår S. Kooi E. Geurts J. van der Valk P. et al. (2010) Upregulation of immunoglobulin-related genes in cortical sections from multiple sclerosis patients. Brain Path 20: 720–729.
328. Tracy S. Kakalacheva K. Lünemann J. Luzuriaga K. Middeldorp J. Thorley-Lawson D. (2012) Persistence of Epstein–Barr virus in self-reactive memory B cells. J Virol 86: 12330–12340.
329. Triantafyllou N. Lambrinoudaki I. Thoda P. Andreadou E. Kararizou E. Alexandrou A. et al. (2012) Lack of association between vitamin D levels and bone mineral density in patients with multiple sclerosis. J Neurol Sci 313: 137–141.
330. Tselis A. (2012) Epstein–Barr virus cause of multiple sclerosis. Curr Opin Rheumatol 24: 424–428.
331. Tulic M. Andrews D. Crook M. Charles A. Tourigny M. Moqbel R. et al. (2012) Changes in thymic regulatory T-cell maturation from birth to puberty: differences in atopic children. J Allergy Clin Immunol 129: 199–206.
332. Tzartos J. Khan G. Vossenkamper A. Cruz-Sadaba M. Lonardi S. Sefia E. et al. (2012) Association of innate immune activation with latent Epstein-Barr virus in active MS lesions. Neurology 78: 15–23.
333. Urry Z. Chambers E. Xystrakis E. Dimeloe S. Richards D. Gabryšová L. et al. (2012) The role of 1α,25-dihydroxyvitamin D 3 and cytokines in the promotion of distinct Foxp3(+) and IL-10(+) CD4(+) T cells. Eur J Immunol 42: 2697–2708.
334. Välimäki V. Löyttyniemi E. Välimäki M. (2007) Vitamin D fortification of milk products does not resolve hypovitaminosis D in young Finnish men. Eur J Clin Nutr 61: 493–497.
335. van Amerongen B. Dijkstra C. Lips P. Polman C. (2004) Multiple sclerosis and vitamin D: an update. Eur J Clin Nutr 58: 1095–1109.
336. van der Mei I. Dore D. Winzenberg T. Blizzard L. Jones G. (2012 a) Vitamin D deficiency in Tasmania: a whole life perspective. Intern Med J 42: 1137–1144.
337. van der Mei I. Ponsonby A. Blizzard L. Dwyer T. (2001) Regional variation in multiple sclerosis prevalence in Australia and its association with ambient ultraviolet radiation. Neuroepidemiology 20: 168–174.
338. 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: 1–6.
339. van der Mei I. Ponsonby A. Dwyer T. Blizzard L. Taylor B. Kilpatrick T. et al. (2007 a) Vitamin D levels in people with multiple sclerosis and community controls in Tasmania, Australia. J Neurol 254: 581–590.
340. van der Mei I. Ponsonby A. Engelsen O. Pasco J. McGrath J. Eyles W. et al. (2007 b) The high prevalence of vitamin D insufficiency across Australian population is only partly explained by season and latitude. Environ Health Perspect 115: 1132–1139.
341. van der Mei I. Simpson S. Jr Knippenberg S. Winzenberg T. Taylor B. (2012 b) Role of vitamin D in multiple sclerosis: implications for disease management. Neuroden Dis Manage 1: 523–536.
342. 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: 546–551.
343. van Etten E. Mathieu C. (2005) Immunoregulation by 1,25-dihydroxyvitamin D3: basic concepts. J Steroid Biochem Mol Biol 97: 93–101.
344. van Etten E. Stoffels K. Gysemans C. Mathieu C. Overbergh L. (2008) Regulation of vitamin D homeostasis: implications for the immune system. Nutr Rev 66(10 Suppl. 2): S125–S134.
345. Vatanparast H. Calvo M. Green T. Whiting S. (2010) Despite mandatory fortification of staple food, vitamin D intakes of Canadian children and adults are inadequate. J Steroid Biochem Mol Biol 121: 301–303.
346. Vedman C. Cantorma M. de Luca H. (2000) Expression of 1,25-dihydroxyvitamin D (3) receptor in the immune system. Arch Biochem Biophys 374: 334–338.
347. Vieth R. (1999) Vitamin D supplementation, 25-hydoxyvitamin D concentrations, and safety. Am J Clin Nutr 69: 842–849.
348. Vieth R. (2006) What is the optimal vitamin D status for health? Prog Biophys Mol Biol 92: 26–32.
349. Vieth R. (2007) Vitamin D toxicity, policy and science. J Bone Mineral Res 22(Suppl. 2): V64–V68.
350. Vieth R. Bischoff-Ferrari H. Boucher B. Dawson-Hughes B. Garland C. Heaney R. et al. (2007) The urgent need to recommend an intake of vitamin D that is effective. Am J Clin Nutr 85: 649–650.
351. von Essen M. Kongsbak M. Schjerling P. Olgaard K. Odum N. Geisler C. (2010) Vitamin D controls T cell antigen receptor signaling and activation of human T cells. Nat Immunol 4: 344–349.
352. von Geldern G. Mowry E. (2012) The influence of nutritional factors on the prognosis of multiple sclerosis. Nat Rev Neurol 13: 678–689.
353. Vukusic S. van Bokstael V. Gosselin S. Confavreux C. (2007) Regional variations of multiple sclerosis prevalence in French farmers. J Neurol Neurosurg Psychiatry 78: 707–709.
354. Wagner H. Hennig H. Jabs W. Siekhaus A. Wessel K. Wandinger K. (2000) Altered prevalence and reactivity of anti-Epstein-Barr virus antibodies in patients with multiple sclerosis. Viral Immunol 13: 497–502.
355. Walters M. (1992) New identified actions of the vitamin D endocrine system. Endocr Rev 13: 719–764.
356. Wandinger K. Jabs W. Siekhaus A. Bubel S. Trillenberg P. Wagner H. et al. (2000) Association between clinical disease activity and Epstein-Barr virus reactivation in MS. Neurology 55: 178–184.
357. Wang T. Tavera-Mendoza L. Laperriere D. Libby E. MacLeod N. Nagai Y. (2005) Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D 3 target genes. Mol Endocrinol 19: 2685–2695.
358. Wang Y. Marling S. Zhu J. Severson K. de Luca H. (2012) Development of experimental autoimmune encephalomyelitis (EAE) in mice requires vitamin D and the vitamin D receptor. Proc Natl Acad Sci U S A 109: 8501–8504.
359. Wergeland S. Torkildsen O. Myhr K. Aknes L. Mørk S. Bø L. (2011) Dietary vitamin D 3 supplements reduce demyelination in the cuprizone model. PloS ONE 6: e26262.
360. Whiting S. Calvo M. (2010) Correcting poor vitamin D status: do older adults need higher repletion doses of vitamin D (3) than younger adults? Mol Nutr Food Res 54: 1077–1084.
361. Willer C. Dyment D. Sadovnick A. Rothwell P. Murray T. Ebers G. et al. (2005) Timing of birth and risk of multiple sclerosis: population based study. BMJ 330: 120.
362. Willis S. Stadelmann C. Rodig S. Caron T. Gattenloehner S. Mallozzi S. et al. (2009) Epstein–Barr virus infection is not a characteristic feature of multiple sclerosis brain. Brain 132: 3318–3328.
363. Wingerchuk D. (2012) Smoking: effects on multiple sclerosis susceptibility and disease progression. Ther Adv Neurol Disord 5: 13–22.
364. Wingerchuk D. Lesaux J. Rice J. Kremenchtzky M. Ebers G. (2005) A pilot study of oral calcitriol (1,25-dihydroxyvitamin D3) for relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry 76: 1294–1296.
365. Yetley E. (2008) Assessing the vitamin D status of the US population. Am J Clin Nutr 88: 558S–564S.
366. Yildiz M. Tettenborn B. Putzki N. (2011) Vitamin D levels in Swiss multiple sclerosis patients. Swiss Med Wkly 141: w13192.
367. Yu S. Cantorna M. (2011) Epigenetic reduction in invariant NKT cells following in utero vitamin D deficiency in mice. J Immunol 186: 1384–1390.
368. Zehdner D. Bland R. Williams M. McNinch R. Howie A. Stewart P. et al. (2001) Extrarenal expression of 25-hydoxyvitamin D (3)-1 alpha-hydroxylase. J Clin Endocrinol Metab 86: 888–894.
369. Zerwekh J. (2008) Blood biomarkers on vitamin D status. Am J Clin Nutr 87: 1087S–1091S.
370. Zhang Y. Leung D. Richers B. Liu Y. Remiglio L. Riches D. et al. (2012) Vitamin D inhibits monocyte / macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1. J Immunol 188: 2127–2135.