Clinical Neuroimmunology pp 197-212
Michael J. Bradshaw Michael F. Holick James M. Stankiewicz
Bradshaw M.J., Holick M.F., Stankiewicz J.M.
In: Rizvi S., Cahill J., Coyle P. (eds) Clinical Neuroimmunology. Current Clinical Neurology. Humana, Cham. https://doi.org/10.1007/978-3-030-24436-1_10
Items in both categories Books/Video and Multiple Sclerosis are listed here:
- Vitamin D and Multiple Sclerosis – book chapter – Oct 2019
- Autoimmune and high-dose vitamin D (Dr. Coimbra) - Dr. Mahtani video and transcript - Nov 2020
- High-Dose Vitamin D Therapy – book July 2018
- Vitamin D has treated Multiple Sclerosis and autoimmune diseases for 16 years – Coimbra April 2018
- Multiple Sclerosis and Vitamin D – chapter and entire MS book - Nov 2017
- Multiple Sclerosis and (lots of) Vitamin D - book by patient on Coimbra protocol - Feb 2016
- Video by Dr. Coimbra – 95 percent of auto-immune cured with vitamin D in high doses - April 2014
Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system. Much has been learned about the role of vitamin D in MS, although our understanding remains incomplete. While the precise etiology of MS remains incompletely understood, low vitamin D status is one factor that appears to predispose to the development of MS, and patients with low 25(OH)D levels may be at greater risk of disease activity. Clinical trials are currently underway to more directly address the role of vitamin D supplementation in MS, yet further investigations are needed. This chapter reviews the role of vitamin D in the pathophysiology of MS and the evidence related to clinical outcomes in patients with MS who have vitamin D deficiency.
References
1.
Anderson DW, Ellenberg JH, Leventhal CM, Reingold SC, Rodriguez M, Silberberg DH. Revised estimate of the prevalence of multiple sclerosis in the United States. Ann Neurol. 1992;31(3):333–6.
PubMedCrossRefGoogle Scholar
2.
Pugliatti M, Rosati G, Carton H, Riise T, Drulovic J, Vecsei L, et al. The epidemiology of multiple sclerosis in Europe. Eur J Neurol. 2006;13(7):700–22.
PubMedCrossRefGoogle Scholar
3.
Koch-Henriksen N, Sorensen PS. The changing demographic pattern of multiple sclerosis epidemiology. Lancet Neurol. 2010;9(5):520–32.
PubMedCrossRefGoogle Scholar
4.
Holick MF. Vitamin D: a millenium perspective. J Cell Biochem. 2003;88(2):296–307.
PubMedCrossRefGoogle Scholar
5.
Wacker M, Holick MF. Sunlight and vitamin D: a global perspective for health. Dermatoendocrinol. 2013;5(1):51–108.
PubMedPubMedCentralCrossRefGoogle Scholar
6.
Yetley EA. Assessing the vitamin D status of the US population. Am J Clin Nutr. 2008;88(2):558S–64S.
PubMedCrossRefGoogle Scholar
7.
Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266–81.
PubMedCrossRefGoogle Scholar
8.
Hossein-nezhad A, Holick MF. Vitamin D for health: a global perspective. Mayo Clin Proc. 2013;88(7):720–55.
PubMedPubMedCentralCrossRefGoogle Scholar
9.
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(5):342–57.
PubMedCrossRefGoogle Scholar
10.
Kriegel MA, Manson JE, Costenbader KH. Does vitamin D affect risk of developing autoimmune disease?: a systematic review. Semin Arthritis Rheum. 2011;40(6):512–31.e8.
PubMedCrossRefGoogle Scholar
11.
Pilz S, Verheyen N, Grubler MR, Tomaschitz A, Marz W. Vitamin D and cardiovascular disease prevention. Nat Rev Cardiol. 2016;13(7):404–17.
CrossRefGoogle Scholar
12.
Provvedini DM, Tsoukas CD, Deftos LJ, Manolagas SC. 1,25-dihydroxyvitamin D3 receptors in human leukocytes. Science. 1983;221(4616):1181–3.
PubMedCrossRefGoogle Scholar
13.
Bhalla AK, Amento EP, Clemens TL, Holick MF, Krane SM. Specific high-affinity receptors for 1,25-dihydroxyvitamin D3 in human peripheral blood mononuclear cells: presence in monocytes and induction in T lymphocytes following activation. J Clin Endocrinol Metab. 1983;57(6):1308–10.
PubMedCrossRefGoogle Scholar
14.
Brennan A, Katz DR, Nunn JD, Barker S, Hewison M, Fraher LJ, et al. Dendritic cells from human tissues express receptors for the immunoregulatory vitamin D3 metabolite, dihydroxycholecalciferol. Immunology. 1987;61(4):457–61.
PubMedPubMedCentralGoogle Scholar
15.
Morgan JW, Kouttab N, Ford D, Maizel AL. Vitamin D-mediated gene regulation in phenotypically defined human B cell subpopulations. Endocrinology. 2000;141(9):3225–34.
PubMedCrossRefGoogle Scholar
16.
Chen L, Cencioni MT, Angelini DF, Borsellino G, Battistini L, Brosnan CF. Transcriptional profiling of gamma delta T cells identifies a role for vitamin D in the immunoregulation of the V gamma 9V delta 2 response to phosphate-containing ligands. J Immunol. 2005;174(10):6144–52.
PubMedCrossRefGoogle Scholar
17.
Jeffery LE, Qureshi OS, Gardner D, Hou TZ, Briggs Z, Soskic B, et al. Vitamin D antagonises the suppressive effect of inflammatory cytokines on CTLA-4 expression and regulatory function. PLoS One. 2015;10(7):e0131539.
PubMedPubMedCentralCrossRefGoogle Scholar
18.
Dankers W, Colin EM, van Hamburg JP, Lubberts E. Vitamin D in autoimmunity: molecular mechanisms and therapeutic potential. Front Immunol. 2016;7:697.
PubMedGoogle Scholar
19.
Rolf L, Muris AH, Hupperts R, Damoiseaux J. Illuminating vitamin D effects on B cells—the multiple sclerosis perspective. Immunology. 2016;147(3):275–84.
PubMedPubMedCentralCrossRefGoogle Scholar
20.
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(12):733–43.
PubMedCrossRefPubMedCentralGoogle Scholar
21.
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(5):2405–11.
PubMedCrossRefPubMedCentralGoogle Scholar
22.
Unger WW, Laban S, Kleijwegt FS, van der Slik AR, Roep BO. Induction of Treg by monocyte-derived DC modulated by vitamin D3 or dexamethasone: differential role for PD-L1. Eur J Immunol. 2009;39(11):3147–59.
PubMedCrossRefPubMedCentralGoogle Scholar
23.
Xu H, Soruri A, Gieseler RK, Peters JH. 1,25-Dihydroxyvitamin D3 exerts opposing effects to IL-4 on MHC class-II antigen expression, accessory activity, and phagocytosis of human monocytes. Scand J Immunol. 1993;38(6):535–40.
PubMedCrossRefPubMedCentralGoogle Scholar
24.
Liu PT, Stenger S, Tang DH, Modlin RL. Cutting edge: vitamin D-mediated human antimicrobial activity against Mycobacterium tuberculosis is dependent on the induction of cathelicidin. J Immunol. 2007;179(4):2060–3.
PubMedCrossRefPubMedCentralGoogle Scholar
25.
Chen Y, Liu W, Sun T, Huang Y, Wang Y, Deb DK, et al. 1,25-Dihydroxyvitamin D promotes negative feedback regulation of TLR signaling via targeting microRNA-155-SOCS1 in macrophages. J Immunol. 2013;190(7):3687–95.
PubMedPubMedCentralCrossRefGoogle Scholar
26.
Palmer MT, Lee YK, Maynard CL, Oliver JR, Bikle DD, Jetten AM, et al. Lineage-specific effects of 1,25-dihydroxyvitamin D(3) on the development of effector CD4 T cells. J Biol Chem. 2011;286(2):997–1004.
PubMedCrossRefPubMedCentralGoogle Scholar
27.
Joshi S, Pantalena LC, Liu XK, Gaffen SL, Liu H, Rohowsky-Kochan C, et al. 1,25-dihydroxyvitamin D(3) ameliorates Th17 autoimmunity via transcriptional modulation of interleukin-17A. Mol Cell Biol. 2011;31(17):3653–69.
PubMedPubMedCentralCrossRefGoogle Scholar
28.
Meehan TF, DeLuca HF. The vitamin D receptor is necessary for 1alpha,25-dihydroxyvitamin D(3) to suppress experimental autoimmune encephalomyelitis in mice. Arch Biochem Biophys. 2002;408(2):200–4.
PubMedCrossRefPubMedCentralGoogle Scholar
29.
Sintzel MB, Rametta M, Reder AT. Vitamin D and multiple sclerosis: a comprehensive review. Neurol Ther. 2018;7(1):59–85.
PubMedCrossRefPubMedCentralGoogle Scholar
30.
Correale J, Ysrraelit MC, Gaitan MI. Vitamin D-mediated immune regulation in multiple sclerosis. J Neurol Sci. 2011;311(1–2):23–31.
PubMedCrossRefGoogle Scholar
31.
Spach KM, Hayes CE. Vitamin D3 confers protection from autoimmune encephalomyelitis only in female mice. J Immunol. 2005;175(6):4119–26.
PubMedCrossRefGoogle Scholar
32.
Nashold FE, Spach KM, Spanier JA, Hayes CE. Estrogen controls vitamin D3-mediated resistance to experimental autoimmune encephalomyelitis by controlling vitamin D3 metabolism and receptor expression. J Immunol. 2009;183(6):3672–81.
PubMedCrossRefGoogle Scholar
33.
Hauser SL, Weiner HL, Che M, Shapiro ME, Gilles F, Letvin NL. Prevention of experimental allergic encephalomyelitis (EAE) in the SJL/J mouse by whole body ultraviolet irradiation. J Immunol. 1984;132(3):1276–81.
PubMedGoogle Scholar
34.
Lucas RM, Ponsonby AL. Considering the potential benefits as well as adverse effects of sun exposure: can all the potential benefits be provided by oral vitamin D supplementation? Prog Biophys Mol Biol. 2006;92(1):140–9.
PubMedCrossRefGoogle Scholar
35.
Holick MF. Sunlight, ultraviolet radiation, vitamin D and skin cancer: how much sunlight do we need? Adv Exp Med Biol. 2014;810:1–16.
PubMedGoogle Scholar
36.
Nataf S, Garcion E, Darcy F, Chabannes D, Muller JY, Brachet P. 1,25 Dihydroxyvitamin D3 exerts regional effects in the central nervous system during experimental allergic encephalomyelitis. J Neuropathol Exp Neurol. 1996;55(8):904–14.
PubMedCrossRefGoogle Scholar
37.
Sotirchos ES, Bhargava P, Eckstein C, Van Haren K, Baynes M, Ntranos A, et al. Safety and immunologic effects of high- vs low-dose cholecalciferol in multiple sclerosis. Neurology. 2016;86(4):382–90.
PubMedPubMedCentralCrossRefGoogle Scholar
38.
Tzartos JS, Friese MA, Craner MJ, Palace J, Newcombe J, Esiri MM, et al. Interleukin-17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis. Am J Pathol. 2008;172(1):146–55.
PubMedPubMedCentralCrossRefGoogle Scholar
39.
Armas LA, Hollis BW, Heaney RP. Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004;89(11):5387–91.
PubMedCrossRefGoogle Scholar
40.
Trang HM, Cole DE, Rubin LA, Pierratos A, Siu S, Vieth R. Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2. Am J Clin Nutr. 1998;68(4):854–8.
PubMedCrossRefGoogle Scholar
41.
Heaney RP. The vitamin D requirement in health and disease. J Steroid Biochem Mol Biol. 2005;97(1–2):13–9.
PubMedCrossRefGoogle Scholar
42.
Carpenter TO, Shaw NJ, Portale AA, Ward LM, Abrams SA, Pettifor JM. Rickets. Nat Rev Dis Primers. 2017;3:17101.
PubMedCrossRefGoogle Scholar
43.
Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96(1):53–8.
CrossRefGoogle Scholar
44.
Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911–30.
CrossRefGoogle Scholar
45.
Manson JE, Brannon PM, Rosen CJ, Taylor CL. Vitamin D deficiency – is there really a pandemic? N Engl J Med. 2016;375(19):1817–20.
CrossRefGoogle Scholar
46.
Holick MF. The vitamin D deficiency pandemic: approaches for diagnosis, treatment and prevention. Rev Endocr Metab Disord. 2017;18(2):153–65.
PubMedCrossRefGoogle Scholar
47.
Rosen CJ, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, et al. IOM committee members respond to Endocrine Society vitamin D guideline. J Clin Endocrinol Metab. 2012;97(4):1146–52.
PubMedPubMedCentralCrossRefGoogle Scholar
48.
Pierrot-Deseilligny C, Souberbielle JC. Is hypovitaminosis D one of the environmental risk factors for multiple sclerosis? Brain. 2010;133(Pt 7):1869–88.
PubMedCrossRefGoogle Scholar
49.
Swank RL, Lerstad O, Strom A, Backer J. Multiple sclerosis in rural Norway its geographic and occupational incidence in relation to nutrition. N Engl J Med. 1952;246(19):722–8.
PubMedCrossRefGoogle Scholar
50.
van der Mei IA, Ponsonby AL, Blizzard L, Dwyer T. Regional variation in multiple sclerosis prevalence in Australia and its association with ambient ultraviolet radiation. Neuroepidemiology. 2001;20(3):168–74.
PubMedCrossRefGoogle Scholar
51.
Vukusic S, Van Bockstael V, Gosselin S, Confavreux C. Regional variations in the prevalence of multiple sclerosis in French farmers. J Neurol Neurosurg Psychiatry. 2007;78(7):707–9.
PubMedPubMedCentralCrossRefGoogle Scholar
52.
Westlund K. Distribution and mortality time trend of multiple sclerosis and some other diseases in Norway. Acta Neurol Scand. 1970;46(4):455–83.
PubMedCrossRefGoogle Scholar
53.
Orton SM, Wald L, Confavreux C, Vukusic S, Krohn JP, Ramagopalan SV, et al. Association of UV radiation with multiple sclerosis prevalence and sex ratio in France. Neurology. 2011;76(5):425–31.
PubMedPubMedCentralCrossRefGoogle Scholar
54.
Gale CR, Martyn CN. Migrant studies in multiple sclerosis. Prog Neurobiol. 1995;47(4–5):425–48.
PubMedCrossRefGoogle Scholar
55.
Kurtzke JF, Beebe GW, Norman JE Jr. Epidemiology of multiple sclerosis in US veterans: III. Migration and the risk of MS. Neurology. 1985;35(5):672–8.
PubMedCrossRefGoogle Scholar
56.
Ascherio A, Munger KL. Environmental risk factors for multiple sclerosis. Part II: Noninfectious factors. Ann Neurol. 2007;61(6):504–13.
CrossRefGoogle Scholar
57.
Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006;296(23):2832–8.
CrossRefGoogle Scholar
58.
van der Mei IA, Ponsonby AL, Dwyer T, Blizzard L, Taylor BV, Kilpatrick T, et al. Vitamin D levels in people with multiple sclerosis and community controls in Tasmania, Australia. J Neurol. 2007;254(5):581–90.
PubMedCrossRefGoogle Scholar
59.
Fiddes B, Wason J, Kemppinen A, Ban M, Compston A, Sawcer S. Confounding underlies the apparent month of birth effect in multiple sclerosis. Ann Neurol. 2013;73(6):714–20.
PubMedPubMedCentralCrossRefGoogle Scholar
60.
Grytten N, Torkildsen O, Aarseth JH, Benjaminsen E, Celius EG, Dahl OP, et al. Month of birth as a latitude-dependent risk factor for multiple sclerosis in Norway. Mult Scler. 2013;19(8):1028–34.
PubMedCrossRefGoogle Scholar
61.
Torkildsen O, Grytten N, Aarseth J, Myhr KM, Kampman MT. Month of birth as a risk factor for multiple sclerosis: an update. Acta Neurol Scand Suppl. 2012;(195):58–62.
CrossRefGoogle Scholar
62.
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. 2011;70(1):30–40.
PubMedPubMedCentralCrossRefGoogle Scholar
63.
Munger KL, Aivo J, Hongell K, Soilu-Hanninen M, Surcel HM, Ascherio A. Vitamin D status during pregnancy and risk of multiple sclerosis in offspring of women in the Finnish Maternity Cohort. JAMA Neurol. 2016;73(5):515–9.
PubMedPubMedCentralCrossRefGoogle Scholar
64.
Nielsen NM, Munger KL, Koch-Henriksen N, Hougaard DM, Magyari M, Jorgensen KT, et al. Neonatal vitamin D status and risk of multiple sclerosis: a population-based case-control study. Neurology. 2017;88(1):44–51.
PubMedPubMedCentralCrossRefGoogle Scholar
65.
Salzer J, Hallmans G, Nystrom M, Stenlund H, Wadell G, Sundstrom P. Vitamin D as a protective factor in multiple sclerosis. Neurology. 2012;79(21):2140–5.
PubMedCrossRefGoogle Scholar
66.
Munger KL, Hongell K, Aivo J, Soilu-Hanninen M, Surcel HM, Ascherio A. 25-Hydroxyvitamin D deficiency and risk of MS among women in the Finnish Maternity Cohort. Neurology. 2017;89(15):1578–83.
PubMedPubMedCentralCrossRefGoogle Scholar
67.
Mokry LE, Ross S, Ahmad OS, Forgetta V, Smith GD, Goltzman D, et al. Vitamin D and risk of multiple sclerosis: a Mendelian Randomization Study. PLoS Med. 2015;12(8):e1001866.
PubMedPubMedCentralCrossRefGoogle Scholar
68.
Rhead B, Baarnhielm M, Gianfrancesco M, Mok A, Shao X, Quach H, et al. Mendelian randomization shows a causal effect of low vitamin D on multiple sclerosis risk. Neurol Genet. 2016;2(5):e97.
PubMedPubMedCentralCrossRefGoogle Scholar
69.
Gianfrancesco MA, Stridh P, Rhead B, Shao X, Xu E, Graves JS, et al. Evidence for a causal relationship between low vitamin D, high BMI, and pediatric-onset MS. Neurology. 2017;88(17):1623–9.
PubMedPubMedCentralCrossRefGoogle Scholar
70.
Ueda P, Rafatnia F, Baarnhielm M, Frobom R, Korzunowicz G, Lonnerbro R, et al. Neonatal vitamin D status and risk of multiple sclerosis. Ann Neurol. 2014;76(3):338–46.
PubMedCrossRefGoogle Scholar
71.
Ascherio A, Munger KL. Not too late to take vitamin D supplements. Ann Neurol. 2014;76(3):321–2.
PubMedCrossRefGoogle Scholar
72.
Mowry EM, Krupp LB, Milazzo M, Chabas D, Strober JB, Belman AL, et al. Vitamin D status is associated with relapse rate in pediatric-onset multiple sclerosis. Ann Neurol. 2010;67(5):618–24.
PubMedGoogle Scholar
73.
Runia TF, Hop WC, de Rijke YB, Buljevac D, Hintzen RQ. Lower serum vitamin D levels are associated with a higher relapse risk in multiple sclerosis. Neurology. 2012;79(3):261–6.
CrossRefGoogle Scholar
74.
Simpson S Jr, Taylor B, Blizzard L, Ponsonby AL, Pittas F, Tremlett H, et al. Higher 25-hydroxyvitamin D is associated with lower relapse risk in multiple sclerosis. Ann Neurol. 2010;68(2):193–203.
PubMedGoogle Scholar
75.
Mowry EM, Waubant E, McCulloch CE, Okuda DT, Evangelista AA, Lincoln RR, et al. Vitamin D status predicts new brain magnetic resonance imaging activity in multiple sclerosis. Ann Neurol. 2012;72(2):234–40.
PubMedPubMedCentralCrossRefGoogle Scholar
76.
Mowry EM, Pelletier D, Gao Z, Howell MD, Zamvil SS, Waubant E. Vitamin D in clinically isolated syndrome: evidence for possible neuroprotection. Eur J Neurol. 2016;23(2):327–32.
PubMedCrossRefGoogle Scholar
77.
Martinelli V, Dalla Costa G, Colombo B, Dalla Libera D, Rubinacci A, Filippi M, et al. Vitamin D levels and risk of multiple sclerosis in patients with clinically isolated syndromes. Mult Scler. 2014;20(2):147–55.
PubMedCrossRefGoogle Scholar
78.
Ascherio A, Munger KL, White R, Kochert K, Simon KC, Polman CH, et al. Vitamin D as an early predictor of multiple sclerosis activity and progression. JAMA Neurol. 2014;71(3):306–14.
PubMedPubMedCentralCrossRefGoogle Scholar
79.
Fitzgerald KC, Munger KL, Kochert K, Arnason BG, Comi G, Cook S, et al. Association of vitamin D levels with multiple sclerosis activity and progression in patients receiving interferon beta-1b. JAMA Neurol. 2015;72(12):1458–65.
CrossRefGoogle Scholar
80.
Munger KL, Kochert K, Simon KC, Kappos L, Polman CH, Freedman MS, et al. Molecular mechanism underlying the impact of vitamin D on disease activity of MS. Ann Clin Transl Neurol. 2014;1(8):605–17.
PubMedPubMedCentralCrossRefGoogle Scholar
81.
Stewart N, Simpson S Jr, van der Mei I, Ponsonby AL, Blizzard L, Dwyer T, et al. Interferon-beta and serum 25-hydroxyvitamin D interact to modulate relapse risk in MS. Neurology. 2012;79(3):254–60.
PubMedCrossRefGoogle Scholar
82.
Loken-Amsrud KI, Holmoy T, Bakke SJ, Beiske AG, Bjerve KS, Bjornara BT, et al. Vitamin D and disease activity in multiple sclerosis before and during interferon-beta treatment. Neurology. 2012;79(3):267–73.
PubMedCrossRefGoogle Scholar
83.
Gauthier SA, Glanz BI, Mandel M, Weiner HL. A model for the comprehensive investigation of a chronic autoimmune disease: the multiple sclerosis CLIMB study. Autoimmun Rev. 2006;5(8):532–6.
PubMedCrossRefGoogle Scholar
84.
Rotstein DL, Healy BC, Malik MT, Carruthers RL, Musallam AJ, Kivisakk P, et al. Effect of vitamin D on MS activity by disease-modifying therapy class. Neurol Neuroimmunol Neuroinflamm. 2015;2(6):e167.
PubMedPubMedCentralCrossRefGoogle Scholar
85.
Munger KL, Zhang SM, O’Reilly E, Hernan MA, Olek MJ, Willett WC, et al. Vitamin D intake and incidence of multiple sclerosis. Neurology. 2004;62(1):60–5.
PubMedCrossRefGoogle Scholar
86.
Munger KL, Chitnis T, Frazier AL, Giovannucci E, Spiegelman D, Ascherio A. Dietary intake of vitamin D during adolescence and risk of multiple sclerosis. J Neurol. 2011;258(3):479–85.
PubMedCrossRefGoogle Scholar
87.
Marrie RA, Beck CA. Preventing multiple sclerosis: to (take) vitamin D or not to (take) vitamin D? Neurology. 2017;89(15):1538–9.
PubMedCrossRefGoogle Scholar
88.
Pozuelo-Moyano B, Benito-Leon J, Mitchell AJ, Hernandez-Gallego J. A systematic review of randomized, double-blind, placebo-controlled trials examining the clinical efficacy of vitamin D in multiple sclerosis. Neuroepidemiology. 2013;40(3):147–53.
PubMedCrossRefGoogle Scholar
89.
James E, Dobson R, Kuhle J, Baker D, Giovannoni G, Ramagopalan SV. The effect of vitamin D-related interventions on multiple sclerosis relapses: a meta-analysis. Mult Scler. 2013;19(12):1571–9.
PubMedCrossRefGoogle Scholar
90.
Kampman MT, Steffensen LH, Mellgren SI, Jorgensen L. 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. Mult Scler. 2012;18(8):1144–51.
PubMedCrossRefPubMedCentralGoogle Scholar
91.
Stein MS, Liu Y, Gray OM, Baker JE, Kolbe SC, Ditchfield MR, et al. A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis. Neurology. 2011;77(17):1611–8.
PubMedCrossRefPubMedCentralGoogle Scholar
92.
Shaygannejad V, Janghorbani M, Ashtari F, Dehghan H. Effects of adjunct low-dose vitamin D on relapsing-remitting multiple sclerosis progression: preliminary findings of a randomized placebo-controlled trial. Mult Scler Int. 2012;2012:452541.
PubMedPubMedCentralGoogle Scholar
93.
Mosayebi G, Ghazavi A, Ghasami K, Jand Y, Kokhaei P. Therapeutic effect of vitamin D3 in multiple sclerosis patients. Immunol Investig. 2011;40(6):627–39.
CrossRefGoogle Scholar
94.
Smolders J, Hupperts R, Barkhof F, Grimaldi LM, Holmoy T, Killestein J, et al. Efficacy of vitamin D3 as add-on therapy in patients with relapsing-remitting multiple sclerosis receiving subcutaneous interferon beta-1a: a Phase II, multicenter, double-blind, randomized, placebo-controlled trial. J Neurol Sci. 2011;311(1–2):44–9.
PubMedCrossRefPubMedCentralGoogle Scholar
95.
Hupperts R, Smolders J, Vieth R, Holmøy T, Marhardt K, Schluep M, Killestein J, Barkhof F, Grimaldi LM, Beelke M. High dose cholecalciferol (vitamin D3) oil as add-on therapy in subjects with relapsing-remitting multiple sclerosis (RRMS) receiving subcutaneous interferon β-1a (scIFNβ-1a). Neurology. 2017;88(16 Suppl):S44.005.
Google Scholar
96.
Camu W, Pierrot-Deseilligny C, Hautecoeur P, Besserve A, Deleglise A-SJ, Lehert P, Souberbielle J-C. Cholecalciferol supplementation in relapsing multiple sclerosis patients treated with subcutaneous interferon beta-1a: a randomized controlled trial. Neurology. 2017;88(16 Suppl):S44.004.
Google Scholar
97.
Dorr J, Ohlraun S, Skarabis H, Paul F. Efficacy of vitamin D supplementation in multiple sclerosis (EVIDIMS Trial): study protocol for a randomized controlled trial. Trials. 2012;13:15.
PubMedPubMedCentralCrossRefGoogle Scholar
98.
Bhargava P, Cassard S, Steele SU, Azevedo C, Pelletier D, Sugar EA, et al. The vitamin D to ameliorate multiple sclerosis (VIDAMS) trial: study design for a multicenter, randomized, double-blind controlled trial of vitamin D in multiple sclerosis. Contemp Clin Trials. 2014;39(2):288–93.
PubMedCrossRefGoogle Scholar
99.
Tripkovic L, Lambert H, Hart K, Smith CP, Bucca G, Penson S, et al. Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis. Am J Clin Nutr. 2012;95(6):1357–64.
PubMedPubMedCentralCrossRefGoogle Scholar
100.
Ekwaru JP, Zwicker JD, Holick MF, Giovannucci E, Veugelers PJ. The importance of body weight for the dose response relationship of oral vitamin D supplementation and serum 25-hydroxyvitamin D in healthy volunteers. PLoS One. 2014;9(11):e111265.
PubMedPubMedCentralCrossRefGoogle Scholar
101.
Rosen CJ. Clinical practice. Vitamin D insufficiency. N Engl J Med. 2011;364(3):248–54.
PubMedCrossRefPubMedCentralGoogle Scholar
102.
Burton JM, Kimball S, Vieth R, Bar-Or A, Dosch HM, Cheung R, et al. A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis. Neurology. 2010;74(23):1852–9.
PubMedPubMedCentralCrossRefGoogle Scholar
103.
Jones G. Pharmacokinetics of vitamin D toxicity. Am J Clin Nutr. 2008;88(2):582S–6S.
PubMedCrossRefPubMedCentralGoogle Scholar
104.
Pham TM, Ekwaru JP, Loehr SA, Veugelers PJ. The relationship of serum 25-hydroxyvitamin D and insulin resistance among nondiabetic Canadians: a longitudinal analysis of participants of a preventive health program. PLoS One. 2015;10(10):e0141081.
PubMedPubMedCentralCrossRefGoogle Scholar
105.
Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation. 2008;117(4):503–11.
CrossRefGoogle Scholar
106.
Stolzenberg-Solomon RZ, Jacobs EJ, Arslan AA, Qi D, Patel AV, Helzlsouer KJ, et al. Circulating 25-hydroxyvitamin D and risk of pancreatic cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Am J Epidemiol. 2010;172(1):81–93.
PubMedPubMedCentralCrossRefGoogle Scholar
107.
Melamed ML, Michos ED, Post W, Astor B. 25-Hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med. 2008;168(15):1629–37.
PubMedPubMedCentralCrossRefGoogle Scholar
108.
Ford JA, MacLennan GS, Avenell A, Bolland M, Grey A, Witham M, et al. Cardiovascular disease and vitamin D supplementation: trial analysis, systematic review, and meta-analysis. Am J Clin Nutr. 2014;100(3):746–55.
CrossRefGoogle Scholar
109.
Bjelakovic G, Gluud LL, Nikolova D, Whitfield K, Wetterslev J, Simonetti RG, et al. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev. 2014;(1):CD007470.