Sunlight, Vitamin D, and Multiple Sclerosis

  • C. E. Hayes
Part of the Topics in Neuroscience book series (TOPNEURO)


The biological mechanisms leading to multiple sclerosis (MS) are uncertain, but both genetic and environmental factors contribute to establishment and progression of the disease [1]. Compared with unrelated individuals, biological first-degree relatives of MS patients show a 20- to 40-fold increased risk of disease, and this increased risk is attributable to genetic factors, rather than a transmissible agent [2]. However, 70% of monozygotic twin pairs are discordant for MS, indicating that inheriting MS susceptibility genes is not sufficient for disease development [3]. Thus, MS development requires exposure to one or more environmental risk factors. This suggests that MS may be preventable if these risk factors can be identified and avoided.


Multiple Sclerosis Experimental Autoimmune Encephalomyelitis Multiple Sclerosis Patient Experimental Autoimmune Encephalomyelitis Induction Multiple Sclerosis Risk 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Willer CJ, Ebers, GC (2000) Susceptibility to multiple sclerosis: interplay between genes and environment. Curr Opin Neurol 13:241–247PubMedCrossRefGoogle Scholar
  2. 2.
    Ebers GC, Dyment DA (1998) Genetics of multiple sclerosis. Semin Neurol 18:295–299PubMedCrossRefGoogle Scholar
  3. 3.
    Ebers GC, Bulman DE, Sadovnick AD et al (1986) A population-based study of multiple sclerosis in twins. N Engl J Med 315:1638–1642PubMedCrossRefGoogle Scholar
  4. 4.
    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 Psychiatr Scand 35 [Suppl 147]:132–147CrossRefGoogle Scholar
  5. 5.
    Freedman DM, Dosemeci M, Alavanja MC (2000) Mortality from multiple sclerosis and exposure to residential and occupational solar radiation: a case-control study based on death certificates. Occup Environ Med 57:418–421PubMedCrossRefGoogle Scholar
  6. 6.
    Kurtzke JF, Kurland LT, Goldberg ID (1971) Mortality and migration in multiple sclerosis. Neurology 21:1186–1197PubMedCrossRefGoogle Scholar
  7. 7.
    Ebers GC, Sadovnick AD (1994) The role of genetic factors in multiple sclerosis susceptibility. J Neuroimmunol 54:1–17PubMedCrossRefGoogle Scholar
  8. 8.
    Hammond SR, English DR, McLeod JG (2000) The age-range of risk of developing multiple sclerosis: evidence from a migrant population in Australia. Brain 123:968–974PubMedCrossRefGoogle Scholar
  9. 9.
    Goldberg P (1974) Multiple sclerosis: vitamin D and calcium as environmental determinants of prevalance (a viewpoint). 1. Sunlight, dietary factors and epidemiology. Int J Environ Studies 6:19–27CrossRefGoogle Scholar
  10. 10.
    Hayes CE, Cantorna MT, De Luca HF (1997) Vitamin D and multiple sclerosis. Proc Soc Exp Biol Med 216:21–27PubMedGoogle Scholar
  11. 11.
    Hayes CE (2000) Vitamin D: a natural inhibitor of multiple sclerosis. Proc Nutr Soc 59:531–535PubMedCrossRefGoogle Scholar
  12. 12.
    Fuller KE, Casparian JM (2001) Vitamin D: balancing cutaneous and systemic considerations. South Med J 94:58–64PubMedGoogle Scholar
  13. 13.
    Holick MF (1995) Environmental factors that influence the cutaneous production of vitamin D. Am J Clin Nutr 61:638S–645SPubMedGoogle Scholar
  14. 14.
    Velluz L, Amiard G (1949) Chimie organique-equilibre de reaction entre precalciferol et calciferol. Comptes Rendus de l’Academie des Sciences 228:853Google Scholar
  15. 15.
    Holick M, Schnoes HK, De Luca HF (1971) Identification of 1,25-dihydroxycholecalciferol, a form of vitamin D3 metabolically active in the intestine. Proc Natl Acad Sci U S A 68:803–804PubMedCrossRefGoogle Scholar
  16. 16.
    Norman AW, Myrtle JF, Midgett RJ, Nowicki HG, Williams V, Popjak G (1971) 1,25Dihydroxycholecalciferol: identification of the proposed active form of vitamin D3 in the intestine. Science 173:51–54PubMedCrossRefGoogle Scholar
  17. 17.
    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. J Clin Endocrinol Metab 67:373–378PubMedCrossRefGoogle Scholar
  18. 18.
    Haussier MR, Haussler CA, Jurutka PW, Thompson PD, Hsieh JC, Remus LS, Selznick SH, Whitfield GK (1998) The vitamin D hormone and its nuclear receptor: molecular actions and disease states. J Endocrinol 154 [Supp1]:557–573Google Scholar
  19. 19.
    Jones G, Strugnell SA, De Luca HF (1998) Current understanding of the molecular actions of vitamin D. Physiol Rev 78:1193–1231PubMedGoogle Scholar
  20. 20.
    Steckley JL, Dyment DA, Sadovnick AD, Risch N, Hayes C, Ebers GC (2000) Genetic analysis of vitamin D related genes in Canadian multiple sclerosis patients. Canadian Collaborative Study Group. Neurology 54:729–732PubMedCrossRefGoogle Scholar
  21. 21.
    Arnason A, Jensson O, Skaftadottir I, Birgisdottir B, Gudmundsson G, Johannesson G (1980) HLA types, GC protein and other genetic markers in multiple sclerosis and two other neurological diseases in Iceland. Acta Neurol Scand 62 [Suppl 78]:39–40Google Scholar
  22. 22.
    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. J Neurol Sci 166:47–52PubMedCrossRefGoogle Scholar
  23. 23.
    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 177:65–71PubMedCrossRefGoogle Scholar
  24. 24.
    Nashold FE, Hoag KA, Goverman J, Hayes CE (2001) Rag-l-dependent cells are necessary for 1,25-dihydroxyvitamin D3 prevention of experimental autoimmune encephalomyelitis. J Neuroimmunol 119:16–29PubMedCrossRefGoogle Scholar
  25. 25.
    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 246:721–728CrossRefGoogle Scholar
  26. 26.
    Goldberg P, Fleming MC, Picard EH (1986) Multiple sclerosis: decreased relapse rate through dietary supplementation with calcium, magnesium and vitamin D. Med Hypotheses 21:193–200PubMedCrossRefGoogle Scholar
  27. 27.
    Nordvik I, Myhr KM, Nyland H, Bjerve KS (2000) Effect of dietary advice and n-3 supplementation in newly diagnosed MS patients. Acta Neurol Scand 102:143–149PubMedCrossRefGoogle Scholar
  28. 28.
    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 44:1687–1692PubMedCrossRefGoogle Scholar
  29. 29.
    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 51:1161–1165PubMedCrossRefGoogle Scholar
  30. 30.
    Wuthrich R, Rieder HP (1970) The seasonal incidence of multiple sclerosis in Switzerland. Eur Neurol 3:257–264PubMedCrossRefGoogle Scholar
  31. 31.
    Bamford CR, Sibley WA, Thies C (1983) Seasonal variation of multiple sclerosis exacerbations in Arizona. Neurology 33:697–701PubMedCrossRefGoogle Scholar
  32. 32.
    Goodkin DE, Hertsgaard D (1989) Seasonal variation of multiple sclerosis exacerbations in North Dakota. Arch Neurol 46:1015–1018PubMedCrossRefGoogle Scholar
  33. 33.
    Jin YP, de Pedro-Cuesta J, Soderstrom M, Link H (1999) Incidence of optic neuritis in Stockholm, Sweden, 1990–1995: II. Time and space patterns. Arch Neurol 56:975–980PubMedCrossRefGoogle Scholar
  34. 34.
    Auer DP, Schumann EM, Kumpfel T, Gossl C, Trenkwalder C (2000) Seasonal fluctuations of gadolinium-enhancing magnetic resonance imaging lesions in multiple sclerosis. Ann Neurol 47:276–277PubMedCrossRefGoogle Scholar
  35. 35.
    Embry AF, Snowdon LR, Vieth R (2000) Vitamin D and seasonal fluctuations of gadolinium-enhancing magnetic resonance imaging lesions in multiple sclerosis. Ann Neurol 48:271–272PubMedCrossRefGoogle Scholar
  36. 36.
    Olitsky PK, Yager RH (1949) Experimental disseminated encephalomyelitis in white mice. J Exp Med 90:213PubMedCrossRefGoogle Scholar
  37. 37.
    Cantorna MT, Hayes CE, De Luca HF (1996) 1,25-Dihydroxyvitamin D3 reversibly blocks the progression of relapsing encephalomyelitis, a model of multiple sclerosis. Proc Natl Acad Sci U S A 93:7861–7864PubMedCrossRefGoogle Scholar
  38. 38.
    Cantorna MT, Humpal-Winter J, De Luca HF (1999) Dietary calcium is a major factor in 1,25-dihydroxycholecalciferol suppression of experimental autoimmune encephalomyelitis in mice. J Nutr 129:1966–1971PubMedGoogle Scholar
  39. 39.
    Lemire JM, Archer DC (1991) 1,25-dihydroxyvitamin D3 prevents the in vivo induction of murine experimental autoimmune encephalomyelitis. J Clin Invest 87:1103–1107PubMedCrossRefGoogle Scholar
  40. 40.
    Nashold FE, Miller DJ, Hayes CE (2000) 1,25-dihydroxyvitamin D3 treatment decreases macrophage accumulation in the CNS of mice with experimental autoimmune encephalomyelitis. J Neuroimmunol 103:171–179PubMedCrossRefGoogle Scholar
  41. 41.
    Bhalla AK, Amento EP, Clemens TL, Holick MF, Krane SM (1983) 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 57:1308–1310PubMedCrossRefGoogle Scholar
  42. 42.
    Provvedini DM, Tsoukas CD, Deftos LJ, Manolagas SC (1983) 1,25-dihydroxyvitamin D3 receptors in human leukocytes. Science 221:1181–1183PubMedCrossRefGoogle Scholar
  43. 43.
    Veldman CM, Cantorna, MT, De Luca HF (2000) Expression of 1,25-dihydroxyvitamin D(3) receptor in the immune system. Arch Biochem Biophys 374:334–338PubMedCrossRefGoogle Scholar
  44. 44.
    Reichel H, Koeffler HP, Tobler A, Norman AW (1987) 1 alpha,25-Dihydroxyvitamin D3 inhibits gamma-interferon synthesis by normal human peripheral blood lymphocytes. Proc Natl Acad Sci U S A 84:3385–3389PubMedCrossRefGoogle Scholar
  45. 45.
    Rigby WF, Denome S, Fanger MW (1987) Regulation of lymphokine production and human T lymphocyte activation by 1,25-dihydroxyvitamin D3. Specific inhibition at the level of messenger RNA. J Clin Invest 79:1659–1664PubMedCrossRefGoogle Scholar
  46. 46.
    Rigby WF (1988) The immunobiology of vitamin D. Immunol Today 9:54–58PubMedCrossRefGoogle Scholar
  47. 47.
    Lemire JM, Archer DC, Beck L, Spiegelberg HL (1995) Immunosuppressive actions of 1,25-dihydroxyvitamin D3: preferential inhibition of Th1 functions. J Nutr 125:17045–1708SGoogle Scholar
  48. 48.
    Muller K, Bendtzen K (1996) 1,25-Dihydroxyvitamin D3 as a natural regulator of human immune functions. J Invest Dermatol Symp Proc 1:68–71Google Scholar
  49. 49.
    Lemire J (2000) 1,25-Dihydroxyvitamin D3--a hormone with immunomodulatory properties. Z Rheumatol 59:24–27PubMedCrossRefGoogle Scholar
  50. 50.
    D’Ambrosio D, Cippitelli M, Cocciolo MG, Mazzeo D, Di Lucia P, Lang R, Sinigaglia F, Panina-Bordignon P (1998) Inhibition of IL-12 production by 1,25-dihydroxyvit-amin D3. Involvement of NF-kappaB downregulation in transcriptional repression of the p40 gene. J Clin Invest 101:252–262PubMedCrossRefGoogle Scholar
  51. 51.
    Griffin MD, Lutz WH, Phan VA, Bachman LA, McKean DJ, Kumar R (2000) Potent inhibition of dendritic cell differentiation and maturation by vitamin D analogs. Biochem Biophys Res Commun 270:701–708PubMedCrossRefGoogle Scholar
  52. 52.
    Penna G, Adorini L (2000) 1 Alpha,25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J Immunol 164:2405–2411PubMedGoogle Scholar
  53. 53.
    Piemonti L, Monti P, Sironi M, Fraticelli P, Leone BE, Dal Cin E, Allavena P, Di Carlo V (2000) Vitamin D3 affects differentiation, maturation, and function of human monocyte-derived dendritic cells. J Immunol 164:4443–4451PubMedGoogle Scholar
  54. 54.
    Trinchieri G, Scott P (1999) Interleukin-12: basic principles and clinical applications. Curr Top Microbiol Immunol 238:57–78PubMedCrossRefGoogle Scholar
  55. 55.
    Zamvil SS, Mitchell DJ, Moore AC, Kitamura K, Steinman L, Rothbard JB (1986) T-cell epitope of the autoantigen myelin basic protein that induces encephalomyelitis. Nature 324:258–260PubMedCrossRefGoogle Scholar
  56. 56.
    Goverman J, Woods A, Larson L, Weiner LP, Hood L, Zaller DM (1993) Transgenic mice that express a myelin basic protein-specific T cell receptor develop spontaneous autoimmunity. Cell 72:551–560PubMedCrossRefGoogle Scholar
  57. 57.
    Cantorna MT, Woodward WD, Hayes CE, De Luca HF (1998) 1,25-dihydroxyvitamin D3 is a positive regulator for the two anti-encephalitogenic cytokines TGF-beta 1 and IL-4. J Immunol 160:5314–5319PubMedGoogle Scholar
  58. 58.
    Cantorna MT, Humpal-Winter J, De Luca HF (2000) In vivo upregulation of interleukin-4 is one mechanism underlying the immunoregulatory effects of 1,25-dihydroxyvitamin D(3). Arch Biochem Biophys 377:135–138PubMedCrossRefGoogle Scholar
  59. 59.
    Van de Keere F, Tonegawa S (1998) CD4(+) T cells prevent spontaneous experimental autoimmune encephalomyelitis in anti-myelin basic protein T cell receptor trans-genic mice. J Exp Med 188:1875–1882PubMedCrossRefGoogle Scholar
  60. 60.
    Olivares-Villagomez D, Wang Y, Lafaille JJ (1998) Regulatory CD4(+) T cells expressing endogenous T cell receptor chains protect myelin basic protein-specific transgenic mice from spontaneous autoimmune encephalomyelitis. J Exp Med 188:1883–1894PubMedCrossRefGoogle Scholar
  61. 61.
    Brabb T, von Dassow P, Ordonez N, Schnabel B, Duke B, Goverman J (2000) In situ tolerance within the central nervous system as a mechanism for preventing autoimmunity. J Exp Med 192:871–880PubMedCrossRefGoogle Scholar
  62. 62.
    Pyke DA (1969) The geography of diabetes. Postgrad Med J [Supp1]:796–801Google Scholar
  63. 63.
    Group DERI (1988) Geographic patterns of childhood insulin-dependent diabetes mellitus. Diabetes 37:1113–1119CrossRefGoogle Scholar
  64. 64.
    Green A, Gale EA, Patterson CC et al (1992) Incidence of childhood-onset insulin-dependent diabetes mellitus: the EURODIAB ACE Study. Lancet 339:905–909PubMedCrossRefGoogle Scholar
  65. 65.
    Nystrom L, Dahlquist G, Ostman J, Wall S, Arnqvist H, Blohme G, Lithner F, Littorin B, Schersten B, Wibell L (1992) Risk of developing insulin-dependent diabetes mellitus (IDDM) before 35 years of age: indications of climatological determinants for age at onset. Int J Epidemiol 21:352–358PubMedCrossRefGoogle Scholar
  66. 66.
    Williams DR (1993) Epidemiological and geographic factors in diabetes. Eye 7:202–204PubMedCrossRefGoogle Scholar
  67. 67.
    Dahlquist G, Mustonen L (1994) Childhood onset diabetes--time trends and climatological factors. Int J Epidemiol 23:1234–1241PubMedCrossRefGoogle Scholar
  68. 68.
    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 40:971–975PubMedCrossRefGoogle Scholar
  69. 69.
    Group ES (1999) Vitamin D supplement in early childhood and risk for type I (insulin-dependent) diabetes mellitus. Diabetologia 42:51–54CrossRefGoogle Scholar
  70. 70.
    Mathieu C, Waer M, Laureys J, Rutgeerts O, Bouillon R (1994) Prevention of autoimmune diabetes in NOD mice by 1,25 dihydroxyvitamin D3. Diabetologia 37:552–558PubMedCrossRefGoogle Scholar
  71. 71.
    Sonnenberg A, McCarty DJ, Jacobsen SJ (1991) Geographic variation of inflammatory bowel disease within the United States. Gastroenterology 100:143–149PubMedGoogle Scholar
  72. 72.
    Sonnenberg A, Wasserman IH (1991) Epidemiology of inflammatory bowel disease among U.S. military veterans. Gastroenterology 101:122–130PubMedGoogle Scholar
  73. 73.
    Shivananda S, Lennard-Jones J, Logan R, Fear N, Price A, Carpenter L, van Blankenstein M (1996) Incidence of inflammatory bowel disease across Europe: is there a difference between north and south? Results of the European Collaborative Study on Inflammatory Bowel Disease (EC-IBD). Gut 39:690–697PubMedCrossRefGoogle Scholar
  74. 74.
    Sonnenberg A (1986) Geographic variation in the incidence of and mortality from inflammatory bowel disease. Dis Colon Rectum 29:854–861PubMedCrossRefGoogle Scholar
  75. 75.
    Sonnenberg, A (1990) Occupational distribution of inflammatory bowel disease among German employees. Gut 31:1037–1040PubMedCrossRefGoogle Scholar
  76. 76.
    Sonnenberg A (1990) Occupational mortality of inflammatory bowel disease. Digestion 46:10–18PubMedCrossRefGoogle Scholar
  77. 77.
    Cucino C, Sonnenberg A (2001) Occupational mortality from inflammatory bowel disease in the United States 1991–1996. Am J Gastroenterol 96:1101–1105PubMedGoogle Scholar
  78. 78.
    Asian A, Triadafilopoulos G (1992) Fish oil fatty acid supplementation in active ulcerative colitis: a double-blind, placebo-controlled, crossover study. Am J Gastroenterol 87:432–437PubMedGoogle Scholar
  79. 79.
    Stenson WF, Cort D, Rodgers J, Burakoff R, De Schryver-Kecskemeti K, Gramlich TL, Beeken W (1992) Dietary supplementation with fish oil in ulcerative colitis. Ann Intern Med 116:609–614PubMedGoogle Scholar
  80. 80.
    O’Sullivan MA, O’Morain CA (1998) Nutritional therapy in Crohn’s disease. Inflamm Bowel Dis 4:45–53PubMedCrossRefGoogle Scholar
  81. 81.
    Fournier C, Gepner P, Sadouk M, Charreire J (1990) In vivo beneficial effects of cyclosporin A and 1,25-dihydroxyvitamin D3 on the induction of experimental autoimmune thyroiditis. Clin Immunol Immunopathol 54:53–63PubMedCrossRefGoogle Scholar
  82. 82.
    Lemire JM, Ince A, Takashima M (1992) 1,25-Dihydroxyvitamin D3 attenuates the expression of experimental murine lupus of MRL/l mice. Autoimmunity 12:143–148PubMedCrossRefGoogle Scholar
  83. 83.
    Cantorna MT, Hayes CE, De Luca HF (1998) 1,25-Dihydroxycholecalciferol inhibits the progression of arthritis in murine models of human arthritis. J Nutr 128:68–72PubMedGoogle Scholar
  84. 84.
    Holick MF (2001) Sunlight “D”ilemma: risk of skin cancer or bone disease and muscle weakness. Lancet 357:4–6PubMedCrossRefGoogle Scholar
  85. 85.
    Malabanan A, Veronikis IE, Holick MF (1998) Redefining vitamin D insufficiency. Lancet 351:805–806PubMedCrossRefGoogle Scholar
  86. 86.
    Chapuy MC, Preziosi P, Maamer M, Arnaud S, Galan P, Hercberg S, Meunier PJ (1997) Prevalence of vitamin D insufficiency in an adult normal population. Osteoporos Int 7:439–443PubMedCrossRefGoogle Scholar
  87. 87.
    Vieth R (1999) Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr 69:842–856PubMedGoogle Scholar
  88. 88.
    Holick MF (1998) Vitamin D requirements for humans of all ages: new increased requirements for women and men 50 years and older. Osteoporos Int 8:S24–S29PubMedCrossRefGoogle Scholar
  89. 89.
    Utiger RD (1998) The need for more vitamin D. N Engl J Med 338:828–829PubMedCrossRefGoogle Scholar
  90. 90.
    Glerup H, Mikkelsen K, Poulsen L, Hass E, Overbeck S, Thomsen J, Charles P, Eriksen EF (2000) Commonly recommended daily intake of vitamin D is not sufficient if sunlight exposure is limited. J Intern Med 247:260–268PubMedCrossRefGoogle Scholar
  91. 91.
    Zerath E, Holy X, Gaud R, Schmitt D (1999) Decreased serum levels of 1,25-(OH)2 vitamin D during 1 year of sunlight deprivation in the Antarctic. Eur J Appl Physiol Occup Physiol 79:141–147PubMedCrossRefGoogle Scholar
  92. 92.
    Compston JE (1998) Vitamin D deficiency: time for action. Evidence supports routine supplementation for elderly people and others at risk. BMJ 317:1466–1467PubMedCrossRefGoogle Scholar
  93. 93.
    Vieth R, Chan PC, MacFarlane GD (2001) Efficacy and safety of vitamin D(3) intake exceeding the lowest observed adverse effect level. Am J Clin Nutr 73:288–294PubMedGoogle Scholar
  94. 94.
    Hess AF, Unger LF (1929) Rickets, osteomalacia and tetany. Lea and Febiger, Philadelphia, pp 38–61Google Scholar
  95. 95.
    Hess AF, Unger LF (1921) Cure of infantile rickets by sunlight. JAMA 39:77–82Google Scholar
  96. 96.
    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 1:7–12CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2004

Authors and Affiliations

  • C. E. Hayes

There are no affiliations available

Personalised recommendations