Skip to main content
×
×
Home

Vitamin D: a natural inhibitor of multiple sclerosis

  • Colleen E. Hayes (a1)
Abstract

Inheriting genetic risk factors for multiple sclerosis (MS) is not sufficient to cause this demyelinating disease of the central nervous system; exposure to environmental risk factors is also required. MS may be preventable if these unidentified environmental factors can be avoided. MS prevalence increases with decreasing solar radiation, suggesting that sunlight may be protective in MS. Since the vitamin D endocrine system is exquisitely responsive to sunlight, and MS prevalence is highest where environmental supplies of vitamin D are lowest, we have proposed that the hormone, 1,25-dihydroxycholecalciferol (1,25-(OH)2D3), may protect genetically-susceptible individuals from developing MS. Evidence consistent with this hypothesis comes not only from geographic studies, but also genetic and biological studies. Over-representation of the vitamin D receptor gene b allele was found in Japanese MS patients, suggesting it may confer MS susceptibility. Fish oil is an excellent vitamin D source, and diets rich in fish may lower MS prevalence or severity. Vitamin D deficiency afflicts most MS patients, as demonstrated by their low bone mass and high fracture rates. However, the clearest evidence that vitamin D may be a natural inhibitor of MS comes from experiments with experimental autoimmune encephalomyelitis (EAE), a model of MS. Treatment of mice with 1,25-(OH)2D3 completely inhibited EAE induction and progression. The hormone stimulated the synthesis of two anti-encephalitogenic cytokines, interleukin 4 and transforming growth factor β-1, and influenced inflammatory cell trafficking or apoptosis. If vitamin D is a natural inhibitor of MS, providing supplemental vitamin D to individuals who are at risk for MS would be advisable.

    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Vitamin D: a natural inhibitor of multiple sclerosis
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Vitamin D: a natural inhibitor of multiple sclerosis
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Vitamin D: a natural inhibitor of multiple sclerosis
      Available formats
      ×
Copyright
Corresponding author
Corresponding author:Professor C. E. Hayes, fax +1 608 262 3453, email hayes@biochem.wisc.edu
References
Hide All
Acheson, ED, Bachrach, CA & Wright, FM (1960) Some comments on the relationship of the distribution of multiple sclerosis to latitude, solar radiation and other variables. Acta Psychiatrica Neurologica Scandinavica Suppl. 147, 132147.
Anderson, O, Lygner, P-E, Bergström, T, Andersson, M & Vahlne, A (1993) Viral infections trigger multiple sclerosis relapses: A prospective seroepidemiological study. Journal of Neurology 240, 417422.
Bates, C, Cartlidge, NEF, French, JM, Jackson, HJ, Nightenhale, S, Shaw, DA, Smith, S, Woo, E, Hawkins, SA, Miller, JH, Belin, J, Conroy, DM, Gill, SK, Sidey, M, Smith, AD, Thompson, RHS, Zilkha, K, Gale, M & Sinclair, HM (1989) A double-blind controlled trial of long chain n-3 polyunsaturated fatty acids in the treatment of multiple sclerosis. Journal of Neurology Neurosurgery and Psychiatry 52, 1822.
Branisteanu, DD, Waer, M, Sobis, H, Marcelis, S, Vandeputte, M & Bouillon, R (1995) Prevention of murine experimental allergic encephalomyelitis: cooperative effects of cyclosporine and 1α,25(OH)2D3. Journal of Neuroimmunology 61, 151160.
Cantorna, MT, Hayes, CE & DeLuca, HF (1996) 1,25-Dihydroxyvitamin D3 reversibly blocks the progression of relapsing encephalomyelitis, a model of multiple sclerosis. Proceedings of the National Academy of Sciences USA 93, 78617864.
Cantorna, MT, Humpal-Winter, J & DeLuca, HF (1999) Dietary calcium is a major factor in 1,25-dihydroxycholecalciferol suppression of experimental autoimmune encephalomyelitis in mice. Journal of Nutrition 129, 19661971.
Cantorna, MT, Woodward, WD, Hayes, CE & DeLuca, HF (1998) 1,25-Dihydroxyvitamin D3 is a positive regulator for the two anti-encephalitogenic cytokines TGF-β1 and IL-4. Journal of Immunology 160, 53145319.
Chick, H, Dalyell, EJ, Hume, M, Mackay, HMM & Smith, HH (1922) The etiology of rickets in infants: prophylactic and curative observations at the Vienna University Kinderklinik. Lancet i, 712.
Cosman, F, Nieves, J, Komar, L, Ferrer, G, Herbert, J, Formica, C, Shen, V & Lindsay, R (1998) Fracture history and bone loss in patients with MS. Neurology 51, 11611165.
Davenport, CB (1922) Multiple sclerosis from the standpoint of geographic distribution and race. Archives of Neurology and Psychiatry 8, 5158.
Ebers, GC (1998) The pathogenesis of multiple sclerosis. European Journal of Neurology 5, Suppl. 2, S7S8.
Ebers, GC, Bulman, DE, Sadovnick, AD, Paty, DW, Warren, S, Hader, W, Murray, TJ, Seland, TP, Duquette, P, Gray, T, Nelson, R, Nicolle, M & Brunet, D (1986) A population-based twin study in multiple sclerosis. New England Journal of Medicine 315, 16381642.
Ebers, GC & Dyment, DA (1998) Genetics of multiple sclerosis. Seminars in Neurology 18, 295299.
Ebers, GC & Sadovnick, AD (1994) The role of genetic factors in multiple sclerosis susceptibility. Journal of Neuroimmunology 54, 117.
EURODIAB Substudy 2 Study Group (1999) Vitamin D supplement in early childhood and risk for Type I (insulin-dependent) diabetes mellitus. Diabetologia 42, 5154.
Fukazawa, T, Yabe, I, Kikuchi, S, Sasaki, H, Hamada, T, Miyasaka, K & Tashiro, K (1999) Association of vitamin D receptor gene polymorphism with multiple sclerosis in Japanese. Journal of Neurological Sciences 166, 4752.
Geiger, R (1965) The Climate Near the Ground, pp. 442446. Cambridge, MA: Harvard University Press.
Goldberg, P (1974 a) Multiple sclerosis: Vitamin D and calcium as environmental determinants of prevalence (a viewpoint). Part 1: Sunlight, dietary factors and epidemiology. International Journal of Environmental Studies 6, 1927.
Goldberg, P (1974 b) Multiple sclerosis: Vitamin D and calcium as environmental determinants of prevalence (a viewpoint). Part 2: Biochemical and Genetic Factors. International Journal of Environmental Studies 6, 121129.
Goldberg, P, Fleming, MC & Picard, EM (1986) Multiple sclerosis: decreased relapse rate through dietary supplementation with calcium, magnesium, and vitamin D. Medical Hypotheses 21, 193200.
Hammond, SR, English, DR & McLeod, JG (2000) The age-range of risk of developing multiple sclerosis. Evidence from a migrant population in Australia. Brain 123, 968974.
Haussler, MR, Haussler, CA, Jurutka, PW, Thompson, PD, Hsieh, JC, Remus, LS, Selznick, SH & Whitfield, GK (1997) The vitamin D hormone and its nuclear receptor: molecular actions and disease states. Journal of Endocrinology 154, 557573.
Hayes, CE, Cantorna, MT & DeLuca, HF (1997) Vitamin D and multiple sclerosis. Proceedings of the Society for Experimental Biology and Medicine 216, 2127.
Hess, AF (1929) Rickets, Osteomalacia and Tetany, pp. 3861. Philadephia, PA: Lea & Febiger.
Hess, AF & Unger, LF (1921) Cure of infantile rickets by sunlight. Journal of the American Medical Association 39, 7782.
Holick, MF (1995) Environmental factors that influence the cutaneous production of vitamin D. American Journal of Clinical Nutrition 61, Suppl., 638S645S.
Holick, MF (1998) Vitamin D requirements for humans of all ages: new increased requirements for women and men 50 years and older. Osteoporosis International Suppl. 8, S24S29.
Holick, MF, Schnoes, HK & DeLuca, HF (1971) Identification of 1,25-dihydroxycholecalciferol, a form of vitamin D3 metabolically active in the intestine. Proceedings of the National Academy of Sciences USA 68, 803804.
Inobe, JI, Chen, Y & Weiner, HL (1996) In vivo administration of IL-4 induces TGF-beta-producing cells and protects animals from experimental autoimmune encephalomyelitis. Annals of the New York Academy of Sciences 778, 390392.
Johns, LD, Flanders, KC, Ranges, GE & Sriram, S (1991) Successful treatment of experimental allergic encephalomyelitis with transforming growth factor-β1. Journal of Immunology 147, 17921796.
Kurland, LT (1952) The frequency and geographic distribution of multiple sclerosis as indicated by mortality statistics and morbidity surveys in the United States and Canada. American Journal of Hygiene 55, 457476.
Kurtzke, JF (1967) On the fine structure of the distribution of multiple sclerosis. Acta Neurologica Scandinavica 43, 257282.
Kuruvilla, AP, Shah, R, Hochwald, GM, Liggitt, HD, Palladino, MA & Thorbecke, GJ (1991) Protective effect of transforming growth factor b1 on experimental autoimmune diseases in mice. Proceedings of the National Academy of Sciences USA 88, 29182921.
Lemire, JM & Archer, DC (1991) 1,25-Dihydroxyvitamin D3 suppresses the in vivo induction of murine experimental autoimmune encephalomyelitis. Journal of Clinical Investigation 87, 11031107.
Limburg, CC (1950) Geographic distribution of multiple sclerosis and its estimated prevalence in the US. Proceedings of the Association for Research into Nervous Diseases 28, 1524.
McDermott, MF, Ramachandran, A, Ogunkolade, BW, Aganna, E, Curtis, D, Boucher, BJ, Snehalatha, C & Hitman, GA (1997) Allelic variation in the vitamin D receptor influences susceptibility to IDDM in Indian Asians. Diabetologia 40, 971975.
Malabanan, A, Veronikis, IE & Holick, MF (1998) Redefining vitamin D insufficiency. Lancet 351, 805806.
Nashold, FE, Miller, DJ & Hayes, CE (2000) 1,25-Dihydroxyvitamin D3 treatment decreases macrophage accumulation in the CNS of mice with experimental autoimmune encephalomyelitis. Journal of Neuroimmunology 103, 171179.
Norman, AW, Myrtle, JF, Midgett, RJ, Nowicki, HG, Williams, V & Popjak, G (1971) 1,25-dihydroxycholecalciferol: identification of the proposed active form of vitamin D3 in the intestine. Science 173, 5154.
Noseworthy, JH (1999) Progress in determining the causes and treatment of multiple sclerosis. Nature 399, A40A47.
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, 16871692.
Olitsky, PK & Yager, RH (1949) Experimental disseminated encephalomyelitis in white mice. Journal of Experimental Medicine 90, 213223.
Panitch, HS (1994) Influence of infection on exacerbations of multiple sclerosis. Annals of Neurology 36, S25S28.
Pratt, RTC, Compston, ND & McAlpine, D (1951) The familial incidence of multiple sclerosis and its significance. Brain 74, 191232.
Presthus, J (1960) Report on the multiple sclerosis investigations in West Norway. Acta Psychiatrica Neurologica Scandinavica Suppl. 147, 8892.
Racke, MK, Dhib-Jalbut, S, Cannella, B, Albert, PS, Raine, CS & McFarlin, DE (1991) Prevention and treatment of chronic relapsing experimental allergic encephalomyelitis by transforming growth factor-β1. Journal of Immunology 146, 30123017.
Sibley, WA, Bamford, CR & Clark, K (1985) Clinical viral infections and multiple sclerosis. Lancet i, 13131315.
Steckley, JL, Dyment, DA, Sadovnick, AD, Risch, N, Hayes, C, Ebers, GC and the Canadian Collaborative Study Group (2000) Genetic analysis of vitamin D related genes in Canadian multiple sclerosis patients. Neurology 54, 729732.
Swank, RL, Lerstad, O, Strøm, A & Backer, J (1952) Multiple sclerosis in rural Norway: Its geographic and occupational incidence in relation to nutrition. New England Journal of Medicine 246, 721.
Ulett, G (1948) Geographic distribution of multiple sclerosis. Diseases of the Nervous System 9, 342.
Vieth, R (1999) Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. American Journal of Clinical Nutrition 69, 842856.
Velluz, L & Amiard, G (1949) Chimie organique-equilibre de reaction entre precalciferol et calciferol (Organic chemistry-balance of reaction between precalciferol and calciferol). Comptes Rendus de l'Academie des Sciences 228, 853855.
Webb, AR, Kline, L & Holick, MF (1988) Influence of season and latitude on the cutaneous synthesis of vitamin D3: exposure to winter sunlight in Boston and Edmonton will not promote vitamin D3 synthesis in human skin. Journal of Clinical Endocrinology and Metabolism 67, 373378.
Westlund, K (1970) Distribution and mortality time trend of multiple sclerosis and some other diseases of Norway. Acta Neurologica Scandinavica 46, 455483.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Proceedings of the Nutrition Society
  • ISSN: 0029-6651
  • EISSN: 1475-2719
  • URL: /core/journals/proceedings-of-the-nutrition-society
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed