Abstract
The cause of MS remains unknown, but a number of genetic and environmental risk factors, and their interactions, are thought to contribute to disease risk. A substantial evidence base now exists supporting an association between vitamin D and MS, primarily illustrated by a latitudinal gradient of MS prevalence, a month of birth effect, an interaction of vitamin D with MS-associated genes and the fact that high vitamin D levels have been associated with a reduced MS risk in longitudinal prospective work. The association is primarily based on epidemiological studies which renders the more elusive question of whether this association truly represents causation, or indeed reverse causality in the light of a potentially uncharacterised pro-dromal phase of the disease. The prospect of vitamin D supplementation preventing MS is a very attractive notion, but a number of areas of inconsistencies and unanswered questions exist. Most notably, future work will need to establish appropriate dosing, timing and method of vitamin D supplementation in optimising any potential clinical benefit. In this chapter, we discuss the strong epidemiological and growing mechanistic evidence supporting an association between vitamin D and MS, and aim to highlight areas of current debate and where future efforts would be well worth targeting. Given that MS is currently the most common, and a rising, cause of neurological disability in young adults in the Western world, elucidating the relationship between vitamin D and MS is a necessary priority in aiming to further develop therapeutic and preventative strategies against this disease.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Acheson ED, Bachrach CA, Wright EM (1960) Some comments on the relationship of the distribution of multiple sclerosis to latitude, solar radiation, and other variables. Acta Psychiatr Scand 35(Suppl 147):132–147
Ascherio A, Munger KL, White R, Köchert K, Simon KC, Polman CH, Freedman MS, Hartung HP, Miller DH, Montalbán X, Edan G, Barkhof F, Pleimes D, Radü EW, Sandbrink R, Kappos L, Pohl C (2014) Vitamin D as an early predictor of multiple sclerosis activity and progression. J Am Med Assoc Neurol 71(3):306–314
Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B (2006) Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr 84(1):18–28
Chen TC, Chimeh F, Lu Z, Mathieu J, Person KS, Zhang A, Kohn N, Martinello S, Berkowitz R, Holick MF (2007) Factors that influence the cutaneous synthesis and dietary sources of vitamin D. Arch Biochem Biophys 460:213–217
Correale J, Ysrraelit MC, Gaitan MI (2009) Immunomodulatory effects of vitamin D in multiple sclerosis. Brain 132:1146–1160
Disanto G, Watson CT, Meier UC, Ebers GC, Giovannoni G, Ramagopalan SV (2013) Month of birth and thymic output. J Am Med Assoc Neurol 70(4):527–528
Fiddes B, Wason J, Kemppinen A, Ban M, Compston A, Sawcer S (2013) Confounding underlies the apparent month of birth effect in multiple sclerosis. Ann Neurol 73(6):714–720
Hammond SR, McLeod JG, Millingen KS (1998) The epidemiology of multiple sclerosis in three Australian cities: Perth, Newcastle and Hobart. Brain 111:1–25
Holick MF (2007) Vitamin D deficiency. N Engl J Med 357:266–281
International Multiple Sclerosis Genetics Consortium (IMSGC) et al (2013) Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat Genet 45(11):1353–1360
Kampman MT, Wilsgaard T, Mellgren SI (2007) Outdoor activities and diet in childhood and adolescence relate to MS risk above the Arctic Circle. J Neurol 254(4):471–477
Koch-Henriksen N, Sørensen PS (2010) The changing demographic pattern of multiple sclerosis epidemiology. Lancet Neurol 9(5):520–532
Kurtzke JF, Beebe GW, Norman JE (1985) Epidemiology of multiple sclerosis in US veterans: III. Migration and the risk of MS. Neurology 35:672–678
Mowry EM, Waubant E, McCullock CE, Okuda DT, Evangelista AA, Lincoln RR, Gourraud PA, Brenneman D, Owen MC, Qualley P, Bucci M, Hauser SL, Pelletier D (2012) Vitamin D status predicts new brain magnetic resonance imaging activity in multiple sclerosis. Ann Neurol 72(2):234–240
Munger KL, Zhang SM, O’Reilly E, Hernan MA, Olek MJ, Willett WC, Ascherio A (2004) Vitamin D intake and incidence of multiple sclerosis. Neurology 62(1):60–65
Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A (2006) Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. J Am Med Assoc 296(23):2832–2838
Ramagopalan SV, Link J, Byrnes JK, Dyment DA, Giovannoni G, Hintzen RQ, Sundqvist E, Kockum I, Smestad C, Lie BA, Harbo HF, Padyukov L, Alfredsson L, Olsson T, Sadovnick AD, Hillert J, Ebers GC (2009a) HLA-DRB1 and month of birth in multiple sclerosis. Neurology 73(24):2107–2111
Ramagopalan SV, Maugeri NJ, Handunnetthi L, Lincoln MR, Orton SM, Dyment DA, Deluca GC, Herrera BM, Chao MJ, Sadovnick AD, Ebers GC, Knight JC (2009b) Expression of the multiple sclerosis-associated MHC class II allele HLA-DRB1*1501 is regulated by vitamin D. PLoS Genet 5(2):e1000369
Ramagopalan SV, Dyment DA, Cader MZ, Morrison KM, Disanto G, Morahan JM, Berlanga-Taylor AJ, Handel A, De Luca GC, Sadovnick AD, Lepage P, Montpetit A, Ebers GC (2011) Rare variants in the CYP27B1 gene are associated with multiple sclerosis. Ann Neurol 70(6):881–886
Runia TF, Hop WC, de Rijke YB, Buljevac D, Hintzen RQ (2012) Lower serum vitamin D levels are associated with a higher relapse risk in multiple sclerosis. Neurology 79(3):261–266
Salzer J, Hallmans G, Nyström M, Stenlund H, Wadell G, Sundström P (2012) Vitamin D as a protective factor in multiple sclerosis. Neurology 79(21):2140–2145
Simpson S Jr, Taylor B, Blizzard L, Ponsonby AL, Pittas F, Tremlett H, Dwyer T, Gies P, van der Mei I (2010) Higher 25-hydroxyvitamin D is associated with lower relapse risk in multiple sclerosis. Ann Neurol 68(2):193–203
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
Smolders J, Thewissen M, Peelan E, Menheere P, Cohen JW, Tervaert J, Damoiseaux J, Hupperts R (2009) Vitamin D status is positively correlated with regulatory T cell function in patients with multiple sclerosis. PloS one 4:e6635
Staples J, Ponsonby AL, Lim L (2010) Low maternal exposure to vitamin D in pregnancy, month of birth and risk of multiple sclerosis in offspring: longitudinal analysis. Br Med J 340:c1640
Swank RL, Lerstad O, Strom A, Backer J (1952) Multiple sclerosis in rural Norway: its geographic and occupational incidence in relation to nutrition. N Engl J Med 246:721–728
The International Multiple Sclerosis Genetics Consortium (IMSGC), Wellcome Trust Case Control Consortium 2 (WTCCC2) et al (2011) Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 476:214–219
Torkildsen O, Knappskog PM, Nyland HI, Myhr KM (2008) Vitamin D-dependent rickets as a possible risk factor for multiple sclerosis. Arch Neurol 65:809–811
Tremlett H, van der Mei IA, Pittas F, Blizzard L, Paley G, Mesaros D, Woodbaker R, Nunez M, Dwyer T, Taylor BV, Ponsonby AL (2008) Monthly ambient sunlight, infections and relapse rates in multiple sclerosis. Neuroepidemiology 31(4):271–279
van der Mei I, Ponsonby AL, Dwyer T, Blizzard L, Simmons R, Taylor BV, Butzkueven H, Kilpatrick T (2003) Past exposure to sun, skin phenotype, and risk of multiple sclerosis: case-control study. Br Med J 327:316–321
Willer CJ, Dyment DA, Sadovnick AD, Rothwell PM, Murray TJ, Ebers GC (2005) Canadian Collaborative Study Group. Timing of birth and risk of multiple sclerosis: population based study. Br Med J 340:c1640
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Pakpoor, J., Ramagopalan, S. (2014). Evidence for an Association Between Vitamin D and Multiple Sclerosis. In: La Flamme, A., Orian, J. (eds) Emerging and Evolving Topics in Multiple Sclerosis Pathogenesis and Treatments. Current Topics in Behavioral Neurosciences, vol 26. Springer, Cham. https://doi.org/10.1007/7854_2014_358
Download citation
DOI: https://doi.org/10.1007/7854_2014_358
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-25541-5
Online ISBN: 978-3-319-25543-9
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)