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What is needed to keep persons with multiple sclerosis vitamin D-sufficient throughout the year?

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Abstract

Vitamin D sufficiency has been associated with lower risk of multiple sclerosis and may also have a favorable effect on the course of the disease. The aim of this work was to identify predictors of serum 25-hydroxy vitamin D (25[OH]D) levels in persons with multiple sclerosis (MS) and to assess the effect of high-dose vitamin D3 supplementation on vitamin D status. A 96-week randomized controlled trial was performed to assess the effect of supplementation with 20,000 IU of vitamin D3 weekly on bone mineral density in 68 patients. We collected data on vitamin D intake and UV-exposure and repeatedly measured serum 25(OH)D levels. Half of the participants had sufficient winter vitamin D levels at baseline (≥50 nmol/l). Vitamin D status was predicted by sun exposure during the last 3 months and by ingested vitamin D from diet and supplements. In the placebo group, the proportion of the participants with sufficient levels increased from 55 % in winter to 92 % during the summer. In the intervention group, all participants had winter 25(OH)D levels above 50 nmol/l at the end of the study. MS patients who have no sun exposure and low dietary vitamin D intake during the winter months should be recommended to take vitamin D supplements to achieve serum 25(OH)D levels of at least 50 nmol/l.

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References

  1. Amezcua L, Chung RH, Conti DV, Langer-Gould AM (2012) Vitamin D levels in Hispanics with multiple sclerosis. J Neurol. doi:10.1007/s00415-012-6537-z

    PubMed  Google Scholar 

  2. Baarnhielm M, Hedstrom AK, Kockum I, Sundqvist E, Gustafsson SA, Hillert J, Olsson T, Alfredsson L (2012) Sunlight is associated with decreased multiple sclerosis risk: no interaction with human leukocyte antigen-DRB1*15. Eur J Neurol 19:955–962

    Article  PubMed  CAS  Google Scholar 

  3. Barnes MS, Bonham MP, Robson PJ, Strain JJ, Lowe-Strong AS, Eaton-Evans J, Ginty F, Wallace JM (2007) Assessment of 25-hydroxyvitamin D and 1, 25-dihydroxyvitamin D3 concentrations in male and female multiple sclerosis patients and control volunteers. Mult Scler 13:670–672

    Article  PubMed  CAS  Google Scholar 

  4. Brustad M, Alsaker E, Engelsen O, Aksnes L, Lund E (2004) Vitamin D status of middle-aged women at 65–71 degrees N in relation to dietary intake and exposure to ultraviolet radiation. Public Health Nutr 7:327–335

    PubMed  CAS  Google Scholar 

  5. Brustad M, Sandanger T, Aksnes L, Lund E (2004) Vitamin D status in a rural population of northern Norway with high fish liver consumption. Public Health Nutr 7:783–789

    PubMed  CAS  Google Scholar 

  6. Burton JM, Kimball S, Vieth R, Bar-Or A, Dosch HM, Cheung R, Gagne D, D’Souza C, Ursell M, O’Connor P (2010) A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis. Neurology 74:1852–1859

    Article  PubMed  CAS  Google Scholar 

  7. Compston A, Coles A (2008) Multiple sclerosis. Lancet 372:1502–1517

    Article  PubMed  CAS  Google Scholar 

  8. Correale J, Ysrraelit MC, Gaitan MI (2009) Immunomodulatory effects of Vitamin D in multiple sclerosis. Brain 132:1146–1160

    Article  PubMed  Google Scholar 

  9. 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 51:1161–1165

    Article  PubMed  CAS  Google Scholar 

  10. Dawson-Hughes B, Heaney RP, Holick MF, Lips P, Meunier PJ, Vieth R (2005) Estimates of optimal vitamin D status. Osteoporos Int 16:713–716

    Article  PubMed  CAS  Google Scholar 

  11. Engelsen O, Brustad M, Aksnes L, Lund E (2005) Daily duration of vitamin D synthesis in human skin with relation to latitude, total ozone, altitude, ground cover, aerosols and cloud thickness. Photochem Photobiol 81:1287–1290

    Article  PubMed  CAS  Google Scholar 

  12. Grimnes G, Almaas B, Eggen AE, Emaus N, Figenschau Y, Hopstock LA, Hutchinson MS, Methlie P, Mihailova A, Sneve M, Torjesen P, Wilsgaard T, Jorde R (2010) Effect of smoking on the serum levels of 25-hydroxyvitamin D depends on the assay employed. Eur J Endocrinol 163:339–348

    Article  PubMed  CAS  Google Scholar 

  13. Hagenau T, Vest R, Gissel TN, Poulsen CS, Erlandsen M, Mosekilde L, Vestergaard P (2009) Global vitamin D levels in relation to age, gender, skin pigmentation and latitude: an ecologic meta-regression analysis. Osteoporos Int 20:133–140

    Article  PubMed  CAS  Google Scholar 

  14. Hiremath GS, Cettomai D, Baynes M, Ratchford JN, Newsome S, Harrison D, Kerr D, Greenberg BM, Calabresi PA (2009) Vitamin D status and effect of low-dose cholecalciferol and high-dose ergocalciferol supplementation in multiple sclerosis. Mult Scler 15:735–740

    Article  PubMed  CAS  Google Scholar 

  15. Hjartaker A, Andersen LF, Lund E (2007) Comparison of diet measures from a food-frequency questionnaire with measures from repeated 24-hour dietary recalls. The Norwegian Women and Cancer Study. Public Health Nutr 10:1094–1103

    Article  PubMed  Google Scholar 

  16. Hollis BW (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

    PubMed  CAS  Google Scholar 

  17. Holmoy T, Moen SM, Gundersen TA, Holick MF, Fainardi E, Castellazzi M, Casetta I (2009) 25-hydroxyvitamin D in cerebrospinal fluid during relapse and remission of multiple sclerosis. Mult Scler 15:1280–1285

    Article  PubMed  Google Scholar 

  18. Kampman MT, Steffensen LH, Mellgren SI, Jorgensen L (2012) 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 18(8):1144–1151

    Article  PubMed  Google Scholar 

  19. Kimball SM, Ursell MR, O’Connor P, Vieth R (2007) Safety of vitamin D3 in adults with multiple sclerosis. Am J Clin Nutr 86:645–651

    PubMed  CAS  Google Scholar 

  20. Knippenberg S, Bol Y, Damoiseaux J, Hupperts R, Smolders J (2011) Vitamin D status in patients with MS is negatively correlated with depression, but not with fatigue. Acta Neurol Scand 124:171–175

    Article  PubMed  CAS  Google Scholar 

  21. Kragt J, van Amerongen B, Killestein J, Dijkstra C, Uitdehaag B, Polman C, Lips P (2009) Higher levels of 25-hydroxyvitamin D are associated with a lower incidence of multiple sclerosis only in women. Mult Scler 15:9–15

    Article  PubMed  CAS  Google Scholar 

  22. Loken-Amsrud KI, Holmoy T, Bakke SJ, Beiske AG, Bjerve KS, Bjornara BT, Hovdal H, Lilleas F, Midgard R, Pedersen T, Benth JS, Sandvik L, Torkildsen O, Wergeland S, Myhr KM (2012) Vitamin D and disease activity in multiple sclerosis before and during interferon-beta treatment. Neurology 79(3):267–273

    Article  PubMed  CAS  Google Scholar 

  23. Lonergan R, Kinsella K, Fitzpatrick P, Brady J, Murray B, Dunne C, Hagan R, Duggan M, Jordan S, McKenna M, Hutchinson M, Tubridy N (2011) Multiple sclerosis prevalence in Ireland: relationship to vitamin D status and HLA genotype. J Neurol Neurosurg Psychiatry 82:317–322

    Article  PubMed  CAS  Google Scholar 

  24. Lucas RM, Ponsonby AL, Dear K, Valery PC, Pender MP, Taylor BV, Kilpatrick TJ, Dwyer T, Coulthard A, Chapman C, van der Mei I, Williams D, McMichael AJ (2011) Sun exposure and vitamin D are independent risk factors for CNS demyelination. Neurology 76:540–548

    Article  PubMed  CAS  Google Scholar 

  25. McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, McFarland HF, Paty DW, Polman CH, Reingold SC, Sandberg-Wollheim M, Sibley W, Thompson A, van den Noort S, Weinshenker BY, Wolinsky JS (2001) Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 50:121–127

    Article  PubMed  CAS  Google Scholar 

  26. Meyer HE, Brunvand L, Brustad M, Holvik K, Johansson L, Paulsen JE (2006) Report IS-1408: measures to ensure a good vitamin D status in the population. Norwegian Directorate of Health, Oslo

    Google Scholar 

  27. Munger KL, Ascherio A (2011) Prevention and treatment of MS: studying the effects of vitamin D. Mult Scler 17:1405–1411

    Article  PubMed  CAS  Google Scholar 

  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 44:1687–1692

    Article  PubMed  CAS  Google Scholar 

  29. Orton SM, Morris AP, Herrera BM, Ramagopalan SV, Lincoln MR, Chao MJ, Vieth R, Sadovnick AD, Ebers GC (2008) Evidence for genetic regulation of vitamin D status in twins with multiple sclerosis. Am J Clin Nutr 88:441–447

    PubMed  CAS  Google Scholar 

  30. Ozgocmen S, Bulut S, Ilhan 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

    Article  PubMed  Google Scholar 

  31. Pierrot-Deseilligny C (2009) Clinical implications of a possible role of vitamin D in multiple sclerosis. J Neurol 256:1468–1479

    Article  PubMed  CAS  Google Scholar 

  32. Rosen CJ (2011) Clinical practice. Vitamin D insufficiency. N Engl J Med 364:248–254

    Article  PubMed  CAS  Google Scholar 

  33. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Mayne ST, Rosen CJ, Shapses SA (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

    Article  PubMed  CAS  Google Scholar 

  34. 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

    Article  PubMed  CAS  Google Scholar 

  35. Simpson S Jr, Taylor B, Blizzard L, Ponsonby AL, Pittas F, Tremlett H, Dwyer T, Gies P, van den Mei I (2010) Higher 25-hydroxyvitamin D is associated with lower relapse risk in multiple sclerosis. Ann Neurol 68:193–203

    PubMed  CAS  Google Scholar 

  36. Smolders J, Menheere P, Kessels A, Damoiseaux J, Hupperts R (2008) Association of vitamin D metabolite levels with relapse rate and disability in multiple sclerosis. Mult Scler 14:1220–1224

    Article  PubMed  CAS  Google Scholar 

  37. Soilu-Hanninen M, Airas L, Mononen I, Heikkila A, Viljanen M, Hanninen A (2005) 25-Hydroxyvitamin D levels in serum at the onset of multiple sclerosis. Mult Scler 11:266–271

    Article  PubMed  CAS  Google Scholar 

  38. Soilu-Hanninen M, Aivo J, Lindstrom BM, Elovaara I, Sumelahti ML, Farkkila M, Tienari P, Atula S, Sarasoja T, Herrala L, Keskinarkaus I, Kruger J, Kallio T, Rocca MA, Filippi M (2012) A randomised, double-blind, placebo-controlled trial with vitamin D3 as an add on treatment to interferon beta-1b in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 83:565–571

    Article  PubMed  Google Scholar 

  39. Soilu-Hanninen M, Laaksonen M, Laitinen I, Eralinna JP, Lilius EM, Mononen I (2008) A longitudinal study of serum 25-hydroxyvitamin D and intact parathyroid hormone levels indicate the importance of vitamin D and calcium homeostasis regulation in multiple sclerosis. J Neurol Neurosurg Psychiatry 79:152–157

    Article  PubMed  CAS  Google Scholar 

  40. Steffensen LH, Jorgensen L, Straume B, Mellgren SI, Kampman MT (2011) Can vitamin D supplementation prevent bone loss in persons with MS? A placebo-controlled trial. J Neurol 258:1624–1631

    Article  PubMed  CAS  Google Scholar 

  41. Stein MS, Liu Y, Gray OM, Baker JE, Kolbe SC, Ditchfield MR, Egan GF, Mitchell PJ, Harrison LC, Butzkueven H, Kilpatrick TJ (2011) A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis. Neurology 77:1611–1618

    Article  PubMed  CAS  Google Scholar 

  42. van der Mei I, Ponsonby AL, Dwyer T, Blizzard L, Taylor BV, Kilpatrick T, Butzkueven H, McMichael AJ (2007) Vitamin D levels in people with multiple sclerosis and community controls in Tasmania, Australia. J Neurol 254:581–590

    Article  PubMed  Google Scholar 

  43. Weinstock-Guttman B, Zivadinov R, Ramanathan M (2011) Inter-dependence of vitamin D levels with serum lipid profiles in multiple sclerosis. J Neurol Sci 311:86–91

    Article  PubMed  CAS  Google Scholar 

  44. Yildiz M, Tettenborn B, Putzki N (2011) Vitamin D levels in Swiss multiple sclerosis patients. Swiss Med Wkly 141:w13192

    PubMed  Google Scholar 

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Acknowledgments

We thank the patients for participating in the study. At the University Hospital of North Norway, study nurses Grethe Berg Johnsen and Marianne Røst (Department of Neurology) and May Rokstad Solem, Elin Hanssen, and Trond Isaksen (Clinical Trial Unit) performed measurements and function tests. Inger Sperstad handled files (Clinical Research Department). The Department of Laboratory Medicine analyzed blood samples and provided skilled assistance and support throughout the study. Bjørg Almås performed 25(OH)D measurements (Hormone Laboratory, Haukeland University Hospital, Bergen, Norway). The study received financial support from the University of Tromsø, the Research Council of Norway, and Odd Fellows Research Foundation for Multiple Sclerosis.

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The authors declare that they have no conflict of interest.

Ethical standard

The human studies have been approved by the appropriate ethics commitee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.

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Correspondence to Linn H. Steffensen.

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Steffensen, L.H., Brustad, M. & Kampman, M.T. What is needed to keep persons with multiple sclerosis vitamin D-sufficient throughout the year?. J Neurol 260, 182–188 (2013). https://doi.org/10.1007/s00415-012-6611-6

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  • DOI: https://doi.org/10.1007/s00415-012-6611-6

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