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Multiple Sclerosis is reduced by Vitamin D supplementation (even without Coimbra) – review Dec 2017

Vitamin D and Multiple Sclerosis: A Comprehensive Review.

Neurol Ther. 2017 Dec 14. doi: 10.1007/s40120-017-0086-4. [Epub ahead of print]
Sintzel MB1, Rametta M2, Reder AT3 areder at neurology.bsd.uchicago.edu
1 Medical Communication Services, Erlenbach, Zurich, Switzerland.
2 Bayer HealthCare Pharmaceuticals, Whippany, NJ, USA.
3 Department of Neurology, University of Chicago, Chicago, IL, USA.
A few images from the review



Note: Coimbra protocol typically has a vitamin D goal= = 375 nmol (150 ng)

Red added by VitaminDWiki

Comments by VitaminDWiki
  • The words Coimbra or Brazil do not occur a single time in this review
  • I feel certain that there are more people subscribed to Coimbra MS protocol groups on the web (> 50,000) than all previous MS trial participants combined
  • Trials reviewed in this study use up to 10,000 IU of Vitamin D daily
    Whereas the Coimbra protocol uses far more: 20,000 to 140,000 IU of Vitamin D daily
  • Coimbra does not do randomized controlled trials – for the following reasons
    1) The benefit is given to all with MS (or other autoimmune diseases) - not just the half getting the Vitamin D
    2) The Vitamin D dose size varies by 7X with the individual - not one dose-size fits all
    3) The protocol is not monotherapy (contains more than just Vitamin D)
    4) Vitamin D doses are so high as to cause hypercalcaemia if Calcium were not restricted and lots of water prescribed

Overview MS and vitamin D

MS updates from Brazil

Multiple Sclerosis and (lots of) Vitamin D - book by patient on Coimbra protocol - Feb 2016

contains protocol description and Coimbra protocol Facebook membership
Vitamin D Protocol used by Dr. Coimbra for Multiple Sclerosis etc.
Snips as of April 2016 http://www.vitamindprotocol.com/dr.-coimbra-s-ms-protocol.html

  • 1,000 IU's vitamin D per kilogram as a first approximation
    (apparently increased/decreased depending of resulting vitamin D blood level)
  • Vitamin B2, magnesium glycinate, boron, chromium picolinate, Omega 3 DHA, Zinc, Methylcobalamin form of B12, Choline, etc.
  • Lack of B12 may affect 10%–15% of the general population and may be the most prevalent genetic risk factor for several human diseases
  • Discontinue eating or drinking dairy products or calcium enriched foods or beverages, also no Ca supplements
  • Drink as least 2.5 liters [85 ounces] of fluids, preferably water
  • Required Tests:​ Vitamin D, Parathyroid, Blood calcium, urinary calcium

 Download the PDF from VitaminDWiki

Numerous observational studies have suggested that there is a correlation between the level of serum vitamin D and MS risk and disease activity. To explore this hypothesis, a literature search of large, prospective, observation studies, epidemiological studies, and studies using new approaches such as Mendelian randomization was conducted. Available data and ongoing research included in this review suggest that the level of serum vitamin D affects the risk of developing MS and also modifies disease activity in MS patients. Newer Mendelian randomization analyses suggest there is a causal relationship between low vitamin D level and the risk of MS. Post-hoc evaluations from two phase 3 studies, BENEFIT and BEYOND, support the findings of observational trials. Study limitations identified in this review recognize the need for larger controlled clinical trials to establish vitamin D supplementation as the standard of care for MS patients. Though there is increasing evidence indicating that lower vitamin D levels are associated with increased risk of MS and with greater clinical and brain MRI activity in established MS, the impact of vitamin D supplementation on MS activity remains inadequately investigated.


  1. Munger K, Levin L, Hollis B, Howard N, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006;296(23):2832.
  2. Munger K, Ascherio A. Prevention and treatment of MS: studying the effects of vitamin D. Mult Scler J. 2011;17(12):1405-11.
  3. Munger K, Aivo J, Hongell K, Soilu-Hanninen M, Surcel H, 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.
  4. Ross AC, Manson JE, Abrams SA, 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;96:53-8.
  5. ChemSpider | Search and share chemistry [Internet]. Chemspider.com. 2017 [cited 30 June 2016]. http://www.chemspider.com.
  6. Conlan R, Sherman E. Unraveling the enigma of vitamin D [Internet]. National Academy of Sciences;2000 [cited 28 June 2016].
  7. Ascherio A, Munger K, Simon K. Vitamin D and multiple sclerosis. Lancet Neurol. 2010;9(6):599-612.
  8. Holick M. Vitamin D: a millenium perspective. J Cell Biochem. 2002;88(2):296-307.
  9. Health Quality Ontario. Clinical Utility of Vitamin D Testing: An Evidence-Based Analysis. 2010 p. 193.
  10. Wacker M, Holick M. Vitamin D—effects on skeletal and extraskeletal health and the need for supplementation. Nutrients. 2013;5(1):111-48.
  11. Holick M, Binkley N, Bischoff-Ferrari H, 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.
  12. Yang L, Ma J, Zhang X, Fan Y, Wang L. Protective role of the vitamin D receptor. Cell Immunol. 2012;279(2):160-6.
  13. Hossein-nezhad A, Holick M. Vitamin D for health: a global perspective. Mayo Clin Proc. 2013;88(7):720-55.
  14. Mora J, Iwata M, von Andrian U. Vitamin effects on the immune system: vitamins A and D take centre stage. Nat Rev Immunol. 2008;8(9):685-98.
  15. Pierrot-Deseilligny C, Souberbielle J. Contribution of vitamin D insufficiency to the pathogenesis of multiple sclerosis. Ther Adv Neurol Disor. 2013;6(2):81-116.
  16. Ross A, Taylor C, Yaktine A, Del Valle H. Dietary reference intakes: calcium and vitamin D. Committee to review dietary reference intakes for vitamin D and calcium food and nutrition board [Internet]. Washington, D.C.: National Academy of Sciences;2011 [cited 28 June 2016]. http://www.ncbi.nlm.nih.gov/books/NBK56070/pdf/TOC.pdf.
  17. Houghton L, Vieth R. The case against ergocalciferol (vitamin D2) as a vitamin supplement. The Am J Clin Nutr. 2006;84(4):694-7.
  18. Christakos S, Dhawan P, Liu Y, Peng X, Porta A. New insights into the mechanisms of vitamin D action. J Cell Biochem. 2003;88(4):695-705.
  19. Holick M, Vitamin D. Deficiency. N Engl J Med. 2007;357(3):266-81.
  20. Heaney R. Functional indices of vitamin D status and ramifications of vitamin D deficiency. Am J Clin Nutr. 2004;80(6):1706S-9S.
  21. Heaney R, Davies K, Chen T, Holick M, Barger-Lux M. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutri. 2003;77(1):204-10.
  22. Burton J, Kimball S, Vieth R, et al. A phase I/II dose- escalation trial of vitamin D3 and calcium in multiple sclerosis. Neurology. 2010;74(23):1852-9.
  23. Kimball S, Ursell M, O'Connor P, Vieth R. Safety of vitamin D3 in adults with multiple sclerosis. Am J Clin Nutr. 2007;86(3):645-51.
  24. Smolders J, Peelen E, Thewissen M, et al. Safety and T Cell modulating effects of high dose vitamin D3 supplementation in multiple sclerosis. PLoS One. 2010;5(12):e15235.
  25. Bell D, Crooke M, Hay N, Glendenning P. Prolonged vitamin D intoxication: presentation, pathogenesis and progress. Int Med J. 2013;43(10):1148-50.
  26. Fragoso Y, Adoni T, Damasceno A, et al. Unfavorable outcomes during treatment of multiple sclerosis with high doses of vitamin D. J Neurol Sci. 2014;346(1-2):341-2.
  27. Swank R, Lerstad O, Str0m A, Backer J. Multiple Sclerosis in Rural Norway. N Eng J Med. 1952;246(19):721-8.
  28. Westlund K. Distribution and mortality time trend of multiple sclerosis and some other diseases in Norway. Acta Neurol Scand. 1970;46(4-5):455-83.
  29. van der Mei I, Ponsonby A, 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.
  30. Vukusic S, Van Bockstael V, Gosselin S, Confavreux C. Regional variations in the prevalence of multiple sclerosis in French farmers. J Neurol Neurosurg Psychiatry. 2006;78(7):707-9.
  31. Pierrot-Deseilligny C, Souberbielle J. Is hypovitaminosis D one of the environmental risk factors for multiple sclerosis. Brain. 2010;133(7):1869-88.
  32. Orton S, Wald L, Confavreux C, et al. Association of UV radiation with multiple sclerosis prevalence and sex ratio in France. Neurology. 2011;76(5):425-31.
  33. Kurtzke J, Beebe G, Norman J. Epidemiology of multiple sclerosis in US veterans: III. Migration and the risk of MIS. Neurology. 1985;35(5):672.
  34. Ascherio A, Munger K. Environmental risk factors for multiple sclerosis. Part II: noninfectious factors. Ann Neurol. 2007;61(6):504-13.
  35. Lucas R, Ponsonby A, Dear K, et al. Sun exposure and vitamin D are independent risk factors for CNS demyelination. Neurology. 2011;76(6):540-8.
  36. Hauser S, Weiner H, Che C, Shapiro M, Gilles F, Letvin N. Prevention of experimental allergic encephalomyelitis (EAE) in the SJL/J mouse by whole body ultraviolet irradiation. J Immunol. 1984;132(3):1276-81.
  37. Willer C. Timing of birth and risk of multiple sclerosis: population based study. BMJ. 2005;330(7483):120.
  38. Fiddes B, Wason J, Sawcer S. Confounding in association studies: month of birth and multiple sclerosis. J Neurol. 2014;261(10):1851-6.
  39. Rodriguez Cruz P, Matthews L, Boggild M, et al. Time- and region-specific season of birth effects in multiple sclerosis in the United Kingdom. JAMA Neurol. 2016;73(8):954.
  40. Munger K, Zhang S, O'Reilly E, et al. Vitamin D intake and incidence of multiple sclerosis. Neurology. 2004;62(1):60-5.
  41. Nielsen N, Munger K, Stenager E, Ascherio A. Author response: neonatal vitamin D status and risk of multiple sclerosis: a population-based case-control study. Neurology. 2017;89(4):411.
  42. Mokry L, Ross S, Ahmad O, et al. Vitamin D and risk of multiple sclerosis: a mendelian randomization study. PLOS Med. 2015;12(8):e1001866.
  43. Gianfrancesco M, Stridh P, Rhead B, et al. Evidence for a causal relationship between low vitamin D, high BMI, and pediatric-onset MS. Neurology. 2017;88(17):1623-9.
  44. Jelinek G. Determining causation from observational studies: a challenge for modern neuroepidemiology. Front Neurol. 2017;8:1-3.
  45. Rhead B, Baarnhielm M, Gianfrancesco M, et al. Mendelian randomization shows a causal effect of low vitamin D on multiple sclerosis risk. Neurol Gen. 2016;2(5):e97.
  46. Ueda P, Rafatnia F, Baarnhielm M, et al. Neonatal vitamin D status and risk of multiple sclerosis. Ann Neurol. 2014;76(3):338-46.
  47. Ascherio A, Munger K. Not too late to take vitamin D supplements. Ann Neurol. 2014;76(3):321-2.
  48. Pihl-Jensen G, Frederiksen J. 25-Hydroxyvitamin D levels in acute monosymptomatic optic neuritis: relation to clinical severity, paraclinical findings and risk of multiple sclerosis. J Neurol. 2015;262(7):1646-54.
  49. Marrie R, Daumer M. A gestational dose of vitamin D per day keeps the MS doctor away. Neurology. 2016;88(1):13-4.
  50. Runia T, Hop W, de Rijke Y, Buljevac D, Hintzen R. Lower serum vitamin D levels are associated with a higher relapse risk in multiple sclerosis. Neurology. 2012;79(3):261-6.
  51. Mowry E, Krupp L, Milazzo M, et al. Vitamin D status is associated with relapse rate in pediatric- onset MS. Ann Neurol. 2010;67(5):618-24.
  52. Simpson S, Taylor B, Blizzard L, et al. Higher 25-hydroxyvitamin D is associated with lower relapse risk in MS. Ann Neurol. 2010;68(2):193-203.
  53. Mowry E, Waubant E, McCulloch C, et al. Vitamin D status predicts new brain magnetic resonance imaging activity in multiple sclerosis. Ann Neurol. 2012;72(2):234-40.
  54. Mowry E, Pelletier D, Gao Z, Howell M, Zamvil S, Waubant E. Vitamin D in clinically isolated syndrome: evidence for possible neuroprotection. Eur J Neurol. 2015;23(2):327-32.
  55. Smolders J, Menheere P, Kessels A, Damoiseaux J, Hupperts R. Association of vitamin D metabolite levels with relapse rate and disability in multiple sclerosis. Mult Scler J. 2008;14(9):1220-4.
  56. Harandi A, Shahbeigi S, Pakdaman H, Fereshtehnejad S, Nikravesh E, Jalilzadeh R. Association of serum 25(OH) vitamin D3 concentration with severity of multiple sclerosis. Iran J Neurol [Internet]. 2012 [cited 22 August 2017];11(2):54-58. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC38 29240/.
  57. Shahbeigi S, Pakdaman H, Fereshtehnejad S, Jalil- zadeh G, Heydari M. Serum Vitamin D3 Concentration Correlates with the Severity of Multiple Sclerosis. Int J Prev Med. 2013;4(5):585-91.
  58. Martinelli V, Dalla Costa G, Colombo B, et al. Vitamin D levels and risk of multiple sclerosis in patients with clinically isolated syndromes. Mult Scler J. 2013;20(2):147-55.
  59. Koven N, Cadden M, Murali S, Ross M. Vitamin D and long-term memory in multiple sclerosis. Cogn Behav Neurol. 2013;26(3):155-60.
  60. Ascherio A, Munger K, White R, et al. Vitamin D as an early predictor of multiple sclerosis activity and progression. JAMA Neurol. 2014;71(3):306-14.
  61. Fitzgerald K, Munger K, Kochert K, 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.
  62. Kappos L, Polman C, Freedman M, et al. Treatment with interferon beta-1b delays conversion to clinically definite and McDonald MS in patients with clinically isolated syndromes. Neurology. 2006;67(7):1242-9.
  63. Kappos L, Freedman M, Polman C, et al. Effect of early versus delayed interferon beta-1b treatment on disability after a first clinical event suggestive of multiple sclerosis: a 3-year follow-up analysis of the BENEFIT study. Lancet. 2007;370(9585):389-97.
  64. Kappos L, Freedman M, Polman C, et al. Long-term effect of early treatment with interferon beta-1b after a first clinical event suggestive of multiple sclerosis: 5-year active treatment extension of the phase 3 BENEFIT trial. Lancet Neurol. 2009;8(11):987-97.
  65. McDonald W, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: Guidelines from the international panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50(1):121-7.
  66. Taylor B, Moses H, Paul F, Suarez G, Rametta M. Treatment of multiple sclerosis-relationship between Vitamin D and Interferon b-1b. Eur Neurol Rev. 2015;10(2):124.
  67. Munger K, Kochert K, Simon K, et al. Molecular mechanism underlying the impact of vitamin D on disease activity of MS. Ann Clin Trans Neurol. 2014;1(8):605-17.
  68. Stewart N, Simpson S, van der Mei I, et al. Interferon- and serum 25-hydroxyvitamin D interact to modulate relapse risk in MS. Neurology. 2012;79(3):254-60.
  69. Rotstein D, Healy B, Malik M, et al. Effect of vitamin D on MS activity by disease-modifying therapy class. Neurol Neuroimmunol Neuroinflamm. 2015;2(6):e167.
  70. Loken-Amsrud K, Holmoy T, Bakke S, et al. Vitamin D and disease activity in multiple sclerosis before and during interferon-treatment. Neurology. 2012;79(3):267-73.
  71. Mosayebi G, Ghazavi A, Ghasami K, Jand Y, Kokhaei P. Therapeutic effect of vitamin D3 in multiple sclerosis patients. Immunol Invest. 2011;40(6):627-39.
  72. Stein M, Liu Y, Gray O, et al. A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis. Neurology. 2011;77(17):1611-8.
  73. Kampman M, Steffensen L, Mellgren S, J0rgensen 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 J. 2012;18(8):1144-51.
  74. Shaygannejad V, Janghorbani M, Ashtari F, Deh- ghan 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;2012:1-7.
  75. Soilu-Hanninen M, Aivo J, Lindstrom B, et al. A randomised, double blind, placebo controlled trial with vitamin D3as an add on treatment to interferon b-1b in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry. 2012;83(5):565-71.
  76. Etemadifar M, Janghorbani M. Efficacy of high-dose vitamin D3 supplementation in vitamin D deficient pregnant women with multiple sclerosis: Preliminary findings of a randomized-controlled trial. Iran J Neurol. 2015;14(2):67-73.
  77. Jelinek G, Marck C, Weiland T, Pereira N, van der Meer D, Hadgkiss E. Latitude, sun exposure and vitamin D supplementation: associations with quality of life and disease outcomes in a large international cohort of people with multiple sclerosis. BMC Neurol. 2015;15(1):1-6.
  78. Laursen J, S0ndergaard H, S0rensen P, Sellebjerg F, Oturai A. Vitamin D supplementation reduces relapse rate in relapsing-remitting multiple sclerosis patients treated with natalizumab. Mult Scler Rel Dis. 2016;10:169-73.
  79. Darwish H, Haddad R, Osman S, et al. Effect of vitamin D replacement on cognition in multiple sclerosis patients. Sci Rep. 2017;7:45926.
  80. Smolders J, Hupperts R, Vieth R, et al. High dose cholecalciferol (vitamin D3) oil as add-on therapy in subjects with relapsing-remitting multiple sclerosis receiving subcutaneous interferon b-1a. In: Presented at the European Committee for Treatment and Research in Multiple Sclerosis conference. London, England, September 14-17, 2016. Abstract S166.
  81. Camu W, Pierrot-Deseilligny C, Hautecoeur P, et al. Cholecalciferol supplementation in relapsing multiple sclerosis patients treated with subcutaneous interferon beta-1a: a randomized, controlled trial. In: Presented at the European Committee for treatment and research in multiple sclerosis conference. London, England, September 14-17, 2016. Abstract P750.
  82. Sotirchos E, Bhargava P, Eckstein C, et al. Safety and immunologic effects of high- vs low-dose chole- calciferol in multiple sclerosis. Neurology. 2015;86(4):382-90.
  83. Fox R, Miller D, Phillips J, et al. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med. 2012;367(12):1087-97.
  84. Cohen J, Barkhof F, Comi G, et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med. 2010;362(5):402-15.
  85. James E, Dobson R, Kuhle J, Baker D, Giovannoni G, Ramagopalan S. The effect of vitamin D-related interventions on multiple sclerosis relapses: a metaanalysis. Mult Scler J. 2013;19(12):1571-9.
  86. ClinicalTrials.gov [Internet]. Clinicaltrials.gov. 2017 [cited 30 June 2016]. http://www.clinicaltrials.gov.
  87. 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):1-6.
  88. Bhargava P, Cassard S, Steele S, 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.

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