Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2018 Sep 24;9(9):CD008422.
doi: 10.1002/14651858.CD008422.pub3.

Vitamin D for the management of multiple sclerosis

Vanitha A Jagannath  1 , Graziella Filippini, Carlo Di Pietrantonj, G V Asokan, Edward W Robak, Liz Whamond, Sarah A Robinson
Affiliations
Meta-Analysis

Vitamin D for the management of multiple sclerosis

Vanitha A Jagannath et al. Cochrane Database Syst Rev. .

Abstract

Background: This review is an update of a previously published review, "Vitamin D for the management of multiple sclerosis" (published in the Cochrane Library; 2010, Issue 12). Multiple sclerosis (MS) is characterised by inflammation, demyelination, axonal or neuronal loss, and astrocytic gliosis in the central nervous system (CNS), which can result in varying levels of disability. Some studies have provided evidence showing an association of MS with low levels of vitamin D and benefit derived from its supplementation.

Objectives: To evaluate the benefit and safety of vitamin D supplementation for reducing disease activity in people with MS.

Search methods: We searched the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Specialized Register up to 2 October 2017 through contact with the Information Specialist with search terms relevant to this review. We included references identified from comprehensive electronic database searches and from handsearches of relevant journals and abstract books from conferences.

Selection criteria: We included randomised controlled trials (RCTs) and quasi-RCTs that compared vitamin D versus placebo, routine care, or low doses of vitamin D in patients with MS. Vitamin D was administered as monotherapy or in combination with calcium. Concomitant interventions were allowed if they were used equally in all trial intervention groups.

Data collection and analysis: Two review authors independently extracted data and assessed the methodological quality of studies, while another review author sorted any disagreements. We expressed treatment effects as mean differences (MDs) for continuous outcomes (Expanded Disability Status Scale and number of magnetic resonance imaging (MRI) gadolinium-enhancing T1 lesions), as standardised MDs for health-related quality of life, as rate differences for annualised relapse rates, and as risk differences (RDs) for serious adverse events and minor adverse events, together with 95% confidence intervals (CIs).

Main results: We identified 12 RCTs enrolling 933 participants with MS; 464 were randomised to the vitamin D group, and 469 to the comparator group. Eleven trials tested vitamin D₃, and one trial tested vitamin D₂. Vitamin D₃ had no effect on the annualised relapse rate at 52 weeks' follow-up (rate difference -0.05, 95% CI -0.17 to 0.07; I² = 38%; five trials; 417 participants; very low-quality evidence according to the GRADE instrument); on the Expanded Disability Status Scale at 52 weeks' follow-up (MD -0.25, 95% CI -0.61 to 0.10; I² = 35%; five trials; 221 participants; very low-quality evidence according to GRADE); and on MRI gadolinium-enhancing T1 lesions at 52 weeks' follow-up (MD 0.02, 95% CI -0.45 to 0.48; I² = 12%; two trials; 256 participants; very low-quality evidence according to GRADE). Vitamin D₃ did not increase the risk of serious adverse effects within a range of 26 to 52 weeks' follow-up (RD 0.01, 95% CI -0.03 to 0.04; I² = 35%; eight trials; 621 participants; low-quality evidence according to GRADE) or minor adverse effects within a range of 26 to 96 weeks' follow-up (RD 0.02, 95% CI -0.02 to 0.06; I² = 20%; eight trials; 701 participants; low-quality evidence according to GRADE). Three studies reported health-related quality of life (HRQOL) using different HRQOL scales. One study reported that vitamin D improved ratings on the psychological and social components of the HRQOL scale but had no effects on the physical components. The other two studies found no effect of vitamin D on HRQOL. Two studies reported fatigue using different scales. One study (158 participants) reported that vitamin D₃ reduced fatigue compared with placebo at 26 weeks' follow-up. The other study (71 participants) found no effect on fatigue at 96 weeks' follow-up. Seven studies reported on cytokine levels, four on T-lymphocyte proliferation, and one on matrix metalloproteinase levels, with no consistent pattern of change in these immunological outcomes. The randomised trials included in this review provided no data on time to first treated relapse, number of participants requiring hospitalisation owing to progression of the disease, proportion of participants who remained relapse-free, cognitive function, or psychological symptoms.

Authors' conclusions: To date, very low-quality evidence suggests no benefit of vitamin D for patient-important outcomes among people with MS. Vitamin D appears to have no effect on recurrence of relapse, worsening of disability measured by the Expanded Disability Status Scale (EDSS), and MRI lesions. Effects on health-related quality of life and fatigue are unclear. Vitamin D₃ at the doses and treatment durations used in the included trials appears to be safe, although available data are limited. Seven ongoing studies will likely provide further evidence that can be included in a future update of this review.

PubMed Disclaimer

Conflict of interest statement

Vanitha A Jagannath: none.

Graziella Filippini: none.

Zbys Fedorowicz: none.

GV Asokan: none.

Edward W Robak: none.

Liz Whamond: none.

Carlo Di Pietrantonj: none.

Sarah Robinson: none.

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
1.1
1.1. Analysis
Comparison 1: Vitamin D vs placebo, Outcome 1: Annualised relapse rate
1.2
1.2. Analysis
Comparison 1: Vitamin D vs placebo, Outcome 2: EDSS
1.3
1.3. Analysis
Comparison 1: Vitamin D vs placebo, Outcome 3: Number of MRI gadolinium‐enhancing T1 lesions
1.4
1.4. Analysis
Comparison 1: Vitamin D vs placebo, Outcome 4: QOL
1.5
1.5. Analysis
Comparison 1: Vitamin D vs placebo, Outcome 5: Serious adverse events
1.6
1.6. Analysis
Comparison 1: Vitamin D vs placebo, Outcome 6: Minor adverse events
See this image and copyright information in PMC

Update of

Comment in

References

References to studies included in this review

Achiron 2015 {published data only}
    1. Achiron A, Givon U, Magalashvili D, Dolev M, Liraz Zaltzman S, Kalron A, et al. Effect of alfacalcidol on multiple sclerosis-related fatigue: a randomized, double-blind placebo-controlled study. Multiple Sclerosis (Houndmills, Basingstoke, England) 2015;21(6):767-75. [PMID: ] - PubMed
Ashtari 2016 {published data only}
    1. Ashtari F, Toghianifar N, Zarkesh-Esfahani SH, Mansourian M. High dose vitamin D intake and quality of life in relapsing-remitting multiple sclerosis: a randomized, double-blind, placebo-controlled clinical trial. Neurological Research 2016;38(10):888-92. - PubMed
    1. Ashtari F, Toghianifar N, Zarkesh-Esfahani SH, Mansourian M. Short-term effect of high-dose vitamin D on the level of Interleukin 10 in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled clinical trial. Neuroimmunomodulation 2015;22(6):400-4. - PubMed
    1. Toghianifar N, Ashtari F, Zarkesh-Esfahani SH, Mansourian M. Effect of high dose vitamin D intake on interleukin-17 levels in multiple sclerosis: a randomized, double-blind, placebo-controlled clinical trial. Journal of Neuroimmunology 2015;15(285):125-8. - PubMed
Burton 2010 {published data only}
    1. Burton JM, Kimball S, Vieth R, Bar-Or A, Dosch HM, Cheung R, et al. A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis. Neurology 2010;74(23):1852-9. [DOI: 10.1212/WNL.0b013e3181e1cec2] - DOI - PMC - PubMed
    1. Kimball S, Vieth R, Dosch HM, Bar-Or A, Cheung R, Gagne D, et al. Cholecalciferol plus calcium suppresses abnormal PBMC reactivity in patients with multiple sclerosis. Journal of Clinical Endocrinology and Metabolism 2011;96(9):2826-34. - PMC - PubMed
Etemadir 2015 {published data only}
    1. 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. Iranian Journal of Neurology 2015;14(2):67-73. - PMC - PubMed
Golan 2013 {published data only}
    1. Golan D, Halhal B, Glass-Marmor L, Staun-Ram E, Rozenberg O, Lavi I, et al. Vitamin D supplementation for patients with multiple sclerosis treated with interferon-beta: a randomized controlled trial assessing the effect on flu-like symptoms and immunomodulatory properties. BMC Neurology 2013;13:60. [PMID: ] - PMC - PubMed
Hupperts 2016 {published data only}
    1. Hupperts R. Supplementation of VigantOL® Oil Versus Placebo as Add-on in Patients With Relapsing Remitting Multiple Sclerosis Receiving Rebif® Treatment (SOLAR). https://clinicaltrials.gov/ct2/show/NCT01285401 November 28, 2016 (last update posted).
    1. Muris AH, Smolders J, Rolf L, Thewissen M, Hupperts R, Damoiseaux J. Immune regulatory effects of high dose vitamin D3 supplementation in a randomized controlled trial in relapsing remitting multiple sclerosis patients receiving IFNbeta; the SOLARIUM study. Journal of Neuroimmunology 2016;300:47-56. - PubMed
    1. Smolders J, Hupperts R, Barkhof F, Grimaldi LM, Holmoy T, Killestein J, et al. Efficacy of vitamin D3 as add-on therapy in patients with relapsing-remitting multiple sclerosis receiving subcutaneous interferon beta-1a: a Phase II, multicenter, double-blind, randomized, placebo-controlled trial. Journal of the Neurological Sciences 2011;311(1-2):44-9. [PMID: ] - PubMed
Kampman 2012 {published data only}
    1. Holmoy T, Lindstrom JC, Eriksen EF, Steffensen LH, Kampman MT. High dose vitamin D supplementation does not affect biochemical bone markers in multiple sclerosis - a randomized controlled trial. BMC Neurology 2017;17(1):67. - PMC - PubMed
    1. Kampman MT, Steffensen LH, Mellgren SI, Jorgensen 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. Multiple Sclerosis (Houndmills, Basingstoke, England) 2012;18(8):1144-51. [PMID: ] - PubMed
    1. Røsjø E, Steffensen LH, Jørgensen L, Lindstrøm JC, Šaltytė Benth J, Michelsen AE, et al. Vitamin D supplementation and systemic inflammation in relapsing-remitting multiple sclerosis. Journal of Neurology 2015;262(12):2713-21. - PubMed
    1. Steffensen LH, Jorgensen L, Straume B, Mellgren SI, Kampman MT. Can vitamin D supplementation prevent bone loss in persons with MS? A placebo-controlled trial. Journal of Neurology 2011;258(9):1624-31. - PMC - PubMed
Mosayebi 2011 {published data only}
    1. Mosayebi G, Ghazavi A, Ghasami K, Jand Y, Kokhaei P. Therapeutic effect of vitamin D3 in multiple sclerosis patients. Immunological Investigations 2011;40(6):627-39. [PMID: ] - PubMed
Shaygannejad 2012 {published data only}
    1. Shaygannejad V, Janghorbani M, Ashtari F, Dehghan H. Effects of adjunct low-dose vitamin D on relapsing-remitting multiple sclerosis progression: preliminary findings of a randomized placebo-controlled trial. Multiple Sclerosis International 2012;2012:1-7. [PMID: ] - PMC - PubMed
Soilu‐Hanninen 2012 {published data only}
    1. Aivo J, Lindsrom BM, Soilu-Hanninen M. A randomised, double-blind, placebo-controlled trial with vitamin D3 in MS: subgroup analysis of patients with baseline disease activity despite interferon treatment. Multiple Sclerosis International 2012;2012:1-6. [PMID: ] - PMC - PubMed
    1. Soilu-Hanninen M, Aivo J, Lindstrom BM, Elovaara I, Sumelahti ML, Farkkila M, et al. A randomised, double blind, placebo controlled trial with vitamin D3 as an add on treatment to interferon beta-1b in patients with multiple sclerosis. Journal of Neurology, Neurosurgery, and Psychiatry 2012;83(5):565-71. [PMID: ] - PubMed
Sotirchos 2016 {published data only}
    1. Sotirchos ES, Bhargava P, Eckstein C, Haren K, Baynes M, Ntranos A, et al. Safety and immunologic effects of high- vs low-dose cholecalciferol in multiple sclerosis. Neurology 2016;86(4):382-90. - PMC - PubMed
Stein 2011 {published data only}
    1. Stein MS, Liu Y, Gray OM, Baker JE, Kolbe SC, Ditchfield MR, et al. A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis. Neurology 2011;77(17):1611-8. [PMID: ] - PubMed

References to studies excluded from this review

Lakatos 2000 {published data only}
    1. Lakatos P, Nagy Z, Kiss L, Horvath C, Takacs I, Foldes J, et al. Prevention of corticosteroid-induced osteoporosis by alfacalcidol. Zeitschrift fur Rheumatologie 2000;59(Suppl 1):48-52. [PMID: ] - PubMed
Najafipoor 2015 {published data only}
    1. Najafipoor A, Roghanian R, Zarkesh-Esfahani SH, Bouzari M, Etemadifar M. The beneficial effects of vitamin D3 on reducing antibody titers against Epstein-Barr virus in multiple sclerosis patients. Cellular Immunology 2015;294(1):9-12. - PubMed
Pierrot‐Deseilligny 2012 {published data only}
    1. Pierrot-Deseilligny C, Rivaud-Péchoux S, Clerson P, Paz R, Souberbielle JC. Relationship between 25-OH-D serum level and relapse rate in multiple sclerosis patients before and after vitamin D supplementation. Therapeutic Advances in Neurological Disorders 2012;5(4):187–98. [PMID: ] - PMC - PubMed
Røsjø 2017 {published data only}
    1. Røsjø E, Lossius A, Abdelmagid N, Lindstrom JC, Kampman MT, Jorgensen L, et al. Effect of high-dose vitamin D3 supplementation on antibody responses against Epstein-Barr virus in relapsing-remitting multiple sclerosis. Multiple Sclerosis (Houndmills, Basingstoke, England) 2017;23(3):395-402. - PubMed
Shirvani‐Farsani 2015 {published data only}
    1. Shirvani-Farsani Z, Behmanesh M, Mohammadi SM, Naser Moghadasi A. Vitamin D levels in multiple sclerosis patients: association with TGF-beta2, TGF-betaRI, and TGF-betaRII expression. Life Sciences 2015;1(134):63-7. - PubMed
Wingerchuk 2005 {published data only}
    1. Wingerchuk DM, Lesaux J, Rice GP, Kremenchutzky M, Ebers GC. A pilot study of oral calcitriol (1,25-dihydroxyvitamin D3) for relapsing-remitting multiple sclerosis. Journal of Neurology, Neurosurgery, and Psychiatry 2005;76(9):1294-6. [PMID: ] - PMC - PubMed

References to ongoing studies

NCT01198132 {published data only}
    1. NCT01198132. A Multicentre Study of the Efficacy and Safety of Supplementary Treatment With Cholecalciferol in Patients With Relapsing Multiple Sclerosis Treated With Subcutaneous Interferon Beta-1a 44 µg 3 Times Weekly [A Multicentre, Randomised, Double-blind, Placebo-controlled Study of the Efficacy of Supplementary Treatment With Cholecalciferol (Vitamin D3) in Patients With Relapsing-Multiple Sclerosis (RMS) Treated With Subcutaneous Interferon Beta-1a 44 µg 3 Times Weekly]. https://clinicaltrials.gov/ct2/show/record/NCT01198132, 8 September 2010.
NCT01440062 {published data only}
    1. NCT01440062. Efficacy of Vitamin D Supplementation in Multiple Sclerosis (EVIDIMS) [Phase II Study of Efficacy of Vitamin D Supplementation in Multiple Sclerosis]. https://clinicaltrials.gov/ct2/show/record/NCT01440062, 19 September 2011.
NCT01490502 {published data only}
    1. NCT01490502. Vitamin D Supplementation in Multiple Sclerosis [A Randomized Controlled Trial of Vitamin D Supplementation in Multiple Sclerosis]. https://clinicaltrials.gov/ct2/show/record/NCT01490502, 6 December 2011.
NCT01753375 {published data only}
    1. NCT01753375. Role of Vitamin D on the Relapse Rate of Multiple Sclerosis [Role of Vitamin D in Reducing the Relapse Rate in Patients With Multiple Sclerosis]. https://clinicaltrials.gov/ct2/show/record/NCT01753375, 17 December 2012.
NCT01768039 {published data only}
    1. NCT01768039. Vitamine D in Multiple Sclerosis [Randomised Double Blind Placebo-controlled Trial of Vitamine D Supplement in Multiple Sclerosis]. https://clinicaltrials.gov/ct2/show/record/NCT01768039, 11 January 2013.
NCT01817166 {published data only}
    1. NCT01817166. Efficacy of Cholecalciferol (Vitamin D3) for Delaying the Diagnosis of MS After a Clinically Isolated Syndrome [Multicentric, Randomized, Double-blind Versus Placebo Study Evaluating the Efficacy of Treatment With Cholecalciferol (Vitamin D3) for Delaying the Diagnosis of Multiple Sclerosis (MS) After a Clinically Isolated Syndrome (CIS). Comparison of Conversion Rates After 2 Years]. https://clinicaltrials.gov/ct2/show/record/NCT01817166, 20 March 2010.
O'Connell 2013 {published data only}
    1. O'Connell K, Kelly S, Kinsella K, Jordan S, Kenny O, Murphy D, et al. Dose-related effects of vitamin D on immune responses in patients with clinically isolated syndrome and healthy control participants: study protocol for an exploratory randomized double-blind placebo-controlled trial. Trials 2013;(14):272. [DOI: 10.1186/1745-6215-14-272] - DOI - PMC - PubMed

Additional references

Autier 2014
    1. Autier P, Boniol M, Pizot C, Mullie P. Vitamin D status and ill health: a systematic review. Lancet. Diabetes & Endocrinology 2014;2(1):76-89. [PMID: ] - PubMed
Bartosik‐Psujek 2010
    1. Bartosik-Psujek H, Tabarkiewicz J, Pocinska K, Stelmasiak Z, Rolinski J. Immunomodulatory effects of vitamin D on monocyte-derived dendritic cells in multiple sclerosis. Multiple Sclerosis (Houndmills, Basingstoke, England) 2010;16(12):1513-6. [PMID: ] - PubMed
Bohannon 1987
    1. Bohannon RW, Smith MB. Interrater reliability of a modified Ashworth scale of muscle spasticity. Physical Therapy 1987;67(2):206-7. [PMID: ] - PubMed
CADTH 2016
    1. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health. Vitamin D for the Treatment or Prevention of Multiple Sclerosis: A Review of the Clinical Effectiveness [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK168998, 2016 March 10. [PMID: ] - PubMed
Cella 1996
    1. Cella DF, Dineen K, Arnason B, Reder A, Webster KA, Karabatsos G, et al. Validation of the functional assessment of multiple sclerosis quality of life instrument. Neurology 1996;47(1):129-39. [PMID: ] - PubMed
Danner 2016
    1. Danner OK, Matthews LR, Francis S, Rao VN, Harvey CP, Tobin RP, et al. Vitamin D3 suppresses class II invariant chain peptide expression on activated B-lymphocytes: a plausible mechanism for downregulation of acute inflammatory conditions. Journal of Nutrition and Metablism 2016;2016:4280876. [PMID: ] - PMC - PubMed
Deeks 2011
    1. Deeks JJ, Higgins JPT, Altman DG (editors). Chapter 9. Analysing data and undertaking meta-analyses. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
Dörr 2013
    1. Dörr J, Döring A, Paul F. Can we prevent or treat multiple sclerosis by individualised vitamin D supply? EPMA Journal 2013;4(1):4. [PMID: ] - PMC - PubMed
Embry 2000
    1. Embry AF, Snowdon LR, Vieth R. Vitamin D and seasonal fluctuations of gadolinium-enhancing magnetic resonance imaging lesions in multiple sclerosis. Annals of Neurology 2000;48(2):271-2. [PMID: ] - PubMed
Freedman 2000
    1. Freedman DM, Dosemeci M, Alavanja MC. Mortality from multiple sclerosis and exposure to residential and occupational solar radiation: a case-control study based on death certificates. Occupational and Environmental Medicine 2000;57(6):418-21. [PMID: ] - PMC - PubMed
Ganesh 2013
    1. Ganesh A, Apel S, Metz L, Patten S. The case for vitamin D supplementation in multiple sclerosis. Multiple Sclerosis and Related Disorders 2013;2(4):281-306. [PMID: ] - PubMed
GRADEproGDT 2015 [Computer program]
    1. GRADEpro GDT. Hamilton (ON): GRADE Working Group, McMaster University, 2015. Available at gradepro.org, Version accessed 8/5/18.
Hempel 2017
    1. Hempel S, Graham GD, Fu N, Estrada E, Chen AY, Miake-Lye I, et al. A systematic review of the effects of modifiable risk factor interventions on the progression of multiple sclerosis. Multiple Sclerosis (Houndmills, Basingstoke, England) 2017;23(4):513-24. [PMID: ] - PubMed
Holick 2011
    1. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. Journal of Clinical Endocrinology and Metabolism 2011;96:1911–30. [PMID: ] - PubMed
IOM 2010
    1. Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academy Press, 2010.
IOM 2011
    1. Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press, 2011. - PubMed
James 2013
    1. James E, Dobson R, Kuhle J, Baker D, Giovannoni G, Ramagopalan SV. The effect of vitamin D-related interventions on multiple sclerosis relapses: a meta-analysis. Multiple Sclerosis (Houndmills, Basingstoke, England) 2013;19(12):1571-9. [PMID: ] - PubMed
Johnston 1995
    1. Johnston M, Weinman M, Wright S. Measures in Health Psychology: A User's Portfolio. Windsor: NFER-NELSON, 1995.
Khosravi‐Largani 2018
    1. Khosravi-Largani M, Pourvali-Talatappeh P, Rousta AM, Karimi-Kivi M, Noroozi E, Mahjoob A, et al. A review on potential roles of vitamins in incidence, progression, and improvement of multiple sclerosis. eNeurologicalSci 2018;10:37-44. [PMID: ] - PMC - PubMed
Krupp 1989
    1. Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Archives of Neurology 1989;46(10):1121-3. [PMID: ] - PubMed
Krupp 1995
    1. Krupp LB, Coyle PK, Doscher C, Miller A, Cross AH, Jandorf L, et al. Fatigue therapy in multiple sclerosis: results of a double-blind, randomized, parallel trial of amantadine, pemoline, and placebo. Neurology 1995;45(11):1956-61. [PMID: ] - PubMed
Kurtzke 1983
    1. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an Expanded Disability Status Scale (EDSS). Neurology 1983;33(11):1444-52. [PMID: ] - PubMed
Lysandropoulos 2011
    1. Lysandropoulos AP, Jaquiery E, Jilek S, Pantaleo G, Schluep M, Du Pasquier RA. Vitamin D has a direct immunomodulatory effect on CD8+ T cells of patients with early multiple sclerosis and healthy control subjects. Journal of Neuroimmunology 2011;233(1-2):240-4. [PMID: ] - PubMed
Mahon 2003
    1. Mahon BD, Gordon SA, Cruz J, Cosman F, Cantorna MT. Cytokine profile in patients with multiple sclerosis following vitamin D supplementation. Journal of Neuroimmunology 2003;134(1-2):128-32. [PMID: ] - PubMed
McDonald 2001
    1. McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the international panel on the diagnosis of multiple sclerosis. Annals of Neurology 2001;50(1):121-7. [PMID: ] - PubMed
McNair 1981
    1. McNair DM, Lorr M, Droppleman LF. Manual for the Profile of Mood States. San Diego, CA: Educational and Industrial Testing Service, 1981.
Mirshafiey 2014
    1. Mirshafiey A, Asghari B, Ghalamfarsa G, Jadidi-Niaragh F, Azizi G. The significance of matrix metalloproteinases in the immunopathogenesis and treatment of multiple sclerosis. Sultan Qaboos University Medical Journal 2014;14(1):e13-25. [PMID: ] - PMC - PubMed
Mowry 2010
    1. Mowry EM, Krupp LB, Milazzo M, Chabas D, Strober JB, Belman AL, et al. Vitamin D status is associated with relapse rate in pediatric-onset multiple sclerosis. Annals of Neurology 2010;67(5):618-24. [PMID: ] - PubMed
Munger 2006
    1. Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 2006;296(23):2832-8. [PMID: ] - PubMed
Nielsen 2017
    1. Nielsen NM, Munger KL, Koch-Henriksen N, Hougaard DM, Magyari M, Jørgensen KT, et al. Neonatal vitamin D status and risk of multiple sclerosis: a population-based case-control study. Neurology 2017;88(1):44–51. [PMID: ] - PMC - PubMed
Niino 2008
    1. Niino M, Fukazawa T, Kikuchi S, Sasaki H. Therapeutic potential of vitamin D for multiple sclerosis. Current Medicinal Chemistry 2008;15(5):499-505. [PMID: ] - PubMed
O'Shea 2002
    1. O'Shea JJ, Ma A, Lipsky P. Cytokines and autoimmunity. Nature Reviews. Immunology 2002;2(1):37-45. [PMID: ] - PubMed
Pierrot‐Deseilligny 2017
    1. Pierrot-Deseilligny C, Souberbielle JC. Vitamin D and multiple sclerosis: an update. Multiple Sclerosis and Related Disorders 2017;14:35-45. [PMID: ] - PubMed
Polman 2005
    1. Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria". Annals of Neurology 2005;58(6):840-6. [PMID: ] - PubMed
Polman 2011
    1. Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Annals of Neurology 2011;69:292–302. - PMC - PubMed
Ponsonby 2005
    1. Ponsonby AL, Lucas RM, Mei IA. UVR, vitamin D and three autoimmune diseases-multiple sclerosis, type 1 diabetes, rheumatoid arthritis. Photochemistry and Photobiology 2005;81(6):1267-75. [PMID: ] - PubMed
Poser 1983
    1. Poser CM, Paty DW, Scheinberg L, McDonald WI, Davis FA, Ebers GC, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Annals of Neurology 1983;13(3):227-31. [PMID: ] - PubMed
Pozuelo‐Moyano 2013
    1. Pozuelo-Moyano B, Benito-Leon J, Mitchell AJ, Hernandez-Gallego J. A systematic review of randomized, double-blind, placebo-controlled trials examining the clinical efficacy of vitamin D in multiple sclerosis. Neuroepidemiology 2013;40(3):147-53. [PMID: ] - PMC - PubMed
Rao 1991
    1. Rao SM, Leo GJ, Bernardin L, Unverzagt F. Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction. Neurology 1991;41(5):685-91. [PMID: ] - PubMed
RevMan 2017 [Computer program]
    1. Review Manager 5 (RevMan 5). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2017.
Rosen 2012
    1. Rosen CJ, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, et al. IOM committee members respond to Endocrine Society vitamin D guideline. The journal of clinical endocrinology and metabolism 2012;97(4):1146-52. [PMID: ] - PMC - PubMed
Rosenberg 1965
    1. Rosenberg M. Society and the Adolescent Self-Image. Princeton, NJ: Princeton University Press, 1965.
Rotstein 2000
    1. Rotstein Z, Barak Y, Noy S, Achiron A. Quality of life in multiple sclerosis: development and validation of the 'RAYS' scale and comparison with the SF-36. International Journal for Quality in Health Care 2000;12(6):511-7. [PMID: ] - PubMed
Sandberg 2016
    1. Sandberg L, Biström M, Salzer J, Vågberg M, Svenningsson A, Sundström P. Vitamin D and axonal injury in multiple sclerosis. Multiple Sclerosis 2016;22:1027-31. - PubMed
Schumacker 1965
    1. Schumacker GA, Beebe G, Kibler RF, Kurland LT, Kurtzke JF, McDowell F, et al. Problems of experimental trials of therapy in multiple sclerosis: report by the panel on the evaluation of experimental trials of therapy in multiple sclerosis. Annals of the New York Academy of Sciences 1965;122:552-68. [PMID: ] - PubMed
Schwartz 1993
    1. Schwartz JE, Jandorf L, Krupp LB. The measurement of fatigue: a new instrument. Journal of Psychosomatic Research 1993;37(7):753-62. [PMID: ] - PubMed
Shirazi 2015
    1. Shirazi HA, Rasouli J, Ciric B, Rostami A, Zhang GX. 1,25-dihydroxyvitamin D3 enhances neural stem cell proliferation and oligodendrocyte differentiation. Experimental and Molecular Pathology 2015;98:240-5. - PMC - PubMed
Simpson 2011
    1. Simpson S Jr, Blizzard L, Otahal P, Van der Mei I, Taylor B. Latitude is significantly associated with the prevalence of multiple sclerosis: a meta-analysis. Journal of Neurology, Neurosurgery, and Psychiatry 2011;82(10):1132-41. [PMID: ] - PubMed
Soilu‐Hanninen 2005
    1. Soilu-Hanninen M, Airas L, Mononen I, Heikkila A, Viljanen M, Hanninen A. 25-Hydroxyvitamin D levels in serum at the onset of multiple sclerosis. Multiple Sclerosis (Houndmills, Basingstoke, England) 2005;11(3):266-71. [PMID: ] - PubMed
Thompson 2018
    1. Thompson AJ, Baranzini SE, Geurts J, Hemmer B, Ciccarelli O. Multiple sclerosis. Lancet 2018;391:1622–36. [PMID: ] - PubMed
Ueda 2014
    1. Ueda P, Rafatnia F, Bäärnhielm M, et al. Neonatal vitamin D status and risk of multiple sclerosis. Annals of Neurology 2014;76:338–46. - PubMed
Vickrey 1995
    1. Vickrey BG, Hays RD, Harooni R, Myers LW, Ellison GW. A health-related quality of life measure for multiple sclerosis. Quality of Life Research 1995;4(3):187-206. [PMID: ] - PubMed
Wagner 2017
    1. Wagner CL, Hollis BW, Kotsa K, Fakhoury H, Karras SN. Vitamin D administration during pregnancy as prevention for pregnancy, neonatal and postnatal complications. Reviews in Endocrine & Metabolic Disorders 2017;18(3):307-22. [PMID: ] - PubMed
Zheng 2018
    1. Zheng C, He L, Liu L, Zhu J, Jin T. The efficacy of vitamin D in multiple sclerosis: a meta-analysis. MultIple Sclerosis and Related Disorders 2018;23:56-61. [PMID: ] - PubMed

References to other published versions of this review

Jagannath 2010
    1. Jagannath VA, Fedorowicz Z, Asokan GV, Robak EW, Whamond L. Vitamin D for the management of multiple sclerosis. Cochrane Database of Systematic Reviews 2010, Issue 12. Art. No: CD008422. [DOI: 10.1002/14651858.CD008422] - DOI - PubMed

MeSH terms