Vitamin D deficiency is associated with the incidence and prevalence of a variety of neurologic disorders, including multiple sclerosis. However, available studies to date have not provided convincing evidence that vitamin D treatment improves fatigue and life quality in patients with multiple sclerosis.
To assess the relationship of vitamin D deficiency with health-related quality-of-life issues and fatigue in multiple sclerosis patients.
Vitamin D3 levels were measured in 149 multiple sclerosis patients. In patients with lower than 30 ng/mL levels, vitamin D was administered. Fatigue and health-related quality of life scores were measured at baseline and months 1, 3, 6, and 12 after the beginning of vitamin D3 administration.
Among 149 patients, 90% were vitamin D deficient. After vitamin D supplementation, health-related quality of life and fatigue scores improved significantly. There was a direct association between health-related quality of life with absence of fatigue and vitamin D status at the end of study.
The 90% frequency of multiple sclerosis patients with vitamin D deficiency, together with the significant association of vitamin D status with the absence of fatigue and improved physical and functional well-being, points to vitamin D supplementation as a potential therapy to enhance the patient’s quality of life.
Relevance of the article for predictive, preventive, and personalized medicine
This article emphasizes that vitamin D supplementation can improve clinical outcome in multiple sclerosis patients providing immune modulation and neuroprotection. Identification and correction of vitamin D deficiency has the potential to treat the related quality of life in patients with multiple sclerosis.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price excludes VAT (USA)
Tax calculation will be finalised during checkout.
Pawlitzki M, Neumann J, Kaufmann J, Stadler E, Sweeney-Reed C, Sailer M, et al. Loss of corticospinal tract integrity in early MS disease stages. Neurol Neuroimmunol Neuroinflamm. 2017;4(6):e399.
Wang C, Barnett MH, Yiannikas C, Barton J, Parratt J, You Y, et al. Lesion activity and chronic demyelination are the major determinants of brain atrophy in MS. Neurol Neuroimmunol Neuroinflamm. 2019;6:e593.
Zeydan B, Gu X, Atkinson EJ, Keegan BM, Weinshenker BG, Tillema JM, et al. Cervical spinal cord atrophy: an early marker of progressive MS onset. Neurol Neuroimmunol Neuroinflamm. 2018;5:e435.
Penner IK, Paul F. Fatigue as a symptom or comorbidity of neurological diseases. Nat Rev Neurol. 2017;13(11):662–75.
Lerdal A, Celius EG, Krupp L, Dahl AA. A prospective study of patterns of fatigue in multiple sclerosis. Eur J Neurol. 2007;14(12):1338–43.
Dörr J, Döring A, Paul F. Can we prevent or treat multiple sclerosis by individualised vitamin D supply? EPMA J. 2013;4(1):4.
Rotstein DL, Healy BC, Malik MT, Carruthers RL, Musallam AJ, Kivisakk P, et al. Effect of vitamin D on MS activity by disease-modifying therapy class. Neurol Neuroimmunol Neuroinflamm. 2015;2(6):e167.
Kepczynska K, Zajda M, Lewandowski Z, Przedlacki J, Zakrzewska-Pniewska B. Bone metabolism and vitamin D status in patients with multiple sclerosis. Neurol Neurochir Pol. 2016;50(4):251–7.
Polachini CR, Spanevello RM, Zanini D, Baldissarelli J, Pereira LB, Schetinger MR, et al. Evaluation of delta-aminolevulinic dehydratase activity, oxidative stress biomarkers, and vitamin D levels in patients with multiple sclerosis. Neurotox Res. 2016;29(2):230–42.
Duan S, Lv Z, Fan X, Wang L, Han F, Wang H, et al. Vitamin D status and the risk of multiple sclerosis: a systematic review and meta-analysis. Neurosci Lett. 2014;5(70):108–13.
Behrens JR, Rasche L, Gieß RM, Pfuhl C, Wakonig K, Freitag E, et al. Low 25-hydroxyvitamin D, but not the bioavailable fraction of 25-hydroxyvitamin D, is a risk factor for multiple sclerosis. Eur J Neurol. 2016;23:62–7.
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. Ann Neurol. 2011;69(2):292–302.
Holick M. Vitamin D deficiency. N EngJ Med 2007;266–81.
Kurtzke JF. Rating neurologic impairment in multiple sclerosis An expanded disability status scale (EDSS). Neurology. 1983;33(11):1444–52.
Armutlu K, Korkmaz NC, Keser I, Sumbuloglu V, Akbiyik DI, Guney Z, et al. The validity and reliability of the Fatigue Severity Scale in Turkish multiple sclerosis patients. Int J Rehabil Res. 2007;30(1):81–5.
Ozakbas S, Ormeci B, Idiman E. Utilization of the Multiple Sclerosis Functional Composite in Follow-up: Relationship to Disease Phenotype, Disability and Treatment Strategies. J Neurol Sci. 2005;232:65–9.
Golubnitschaja O, Baban B, Boniolo G, Wang W, Bubnov R, Kapalla M, et al. Medicine in the early twenty-first century: paradigm and anticipation - EPMA position paper 2016. EPMA J. 2016;7:23.
Golubnitschaja O, Costigliola V, EPMA. General report & recommendations in predictive, preventive and personalised medicine 2012: white paper of the European association for predictive, preventive and personalised medicine. EPMA J. 2012;3(1):14.
Veauthier C, Paul F. Sleep disorders in multiple sclerosis and their relationship to fatigue. Sleep Med. 2014;15:5–14.
Pöttgen J, Moss MR, Wendebourg MJ, Feddersen LK, Lau S, Köpke S, Meyer B, Friede T, Penner IK,Heesen C, Gold SM. Randomised controlled trial of a self-guided online fatigue intervention in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2018;1–7.
Gaede G, Tiede M, Lorenz I, Brandt AU, Pfueller C, Dörr J, et al. Safety and preliminary efficacy of deep transcranial magneticstimulation in MS-related fatigue. Neurol Neuroimmunol Neuroinflamm. 2017;5(1):e423.
Brenton JN, Banwell B, Bergqvist AGC, Lehner-Gulotta D, Gampper L, Leytham E, et al. Pilot study of a ketogenic diet in relapsing- remitting MS. Neurol Neuroimmunol Neuroinflamm. 2019;6:e565.
Coe S, Cossington J, Collett J, Soundy A, Izadi H, Ovington M, et al. A randomised double-blind placebo-controlled feasibility trialof flavonoid-rich cocoa for fatigue in people with relapsing and remittingmultiple sclerosis. J Neurol Neurosurg Psychiatry. 2019;90(5):507–13.
Camu W, Lehert P, Pierrot-Deseilligny C, Hautecoeur P, Besserve A, Jean Deleglise AS, et al. Cholecalciferol in relapsing-remitting MS: A randomized clinical trial(CHOLINE). Neurol Neuroimmunol Neuroinflamm. 2019;6(5):e597.
Jagannath VA, Filippini G, Di Pietrantonj C, Asokan GV, Robak EW, Whamond L, et al. Vitamin D for the management of multiple sclerosis. Cochrane Database Syst Rev. 2018;9:CD008422.
Koduah P, Paul F, Dörr JM. Vitamin D in the prevention, prediction and treatment of neurodegenerative and neuroinflammatory diseases. EPMA J. 2017;8(4):313–25.
Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006;296:2832–8.
Martinelli V, Dalla Costa G, Colombo B, Dalla Libera D, Rubinacci A, Filippi M, et al. Vitamin D levels and risk of multiple sclerosis in patients with clinically isolated syndromes. Mult Scler. 2014;20(2):147–55.
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. Ann Neurol. 2010;67(5):618–24.
Simpson S, Taylor B, Blizzard L, Simpson S Jr, Taylor B, Blizzard L, et al. Higher 25-hydroxyvitamin D is associated with lower relapse risk in multiple sclerosis. Ann Neurol. 2010;68(2):193–203.
Ascherio A, Munger KL, White R, Köchert K, et al. Vitamin D as an early predictor of multiple sclerosis activity and progression. JAMA Neurol. 2014;71(3):306–14.
Fitzgerald KC, Munger KL, Köchert K, et al. Association of vitamin D levels with multiple sclerosis activity andprogression in patients receiving Interferon Beta-1b. JAMA Neurol. 2015;72(12):1458–65.
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. Mult Scler. 2015;21(6):767–75.
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. Neurol Res. 2016;38(10):888–92.
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 Neurol. 2013;13:60.
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. Mult Scler. 2012;18(8):1144–51.
Smith MM, Arnett PA. Factors related to employment changes in individuals with multiple sclerosis. Mult Scler. 2005;11(5):602–9.
Veauthier C, Hasselmann H, Gold SM, Paul F. The Berlin Treatment Algorithm: recommendations for tailored innovative therapeutic strategies for multiple sclerosis- related fatigue. EPMA J. 2016;7:25.
Veauthier C, Radbruch H, Gaede G, Pfueller C, Dorr J, Bellmann-Strobl J, et al. Fatigue in multiple sclerosis is closely related to sleep disorders: a polysomnographic cross-sectional study. Mult Scler. 2011;17(5):613–22.
Kaminska M, Kimoff R, Benedetti A, Robinson A, Bar-Or A, Lapierre Y, et al. Obstructive sleep apnea is associated with fatigue in multiple sclerosis. Mult Scler. 2012;18(8):1159–69.
The authors declare that they have no competing interests.
The research did not involve any risk for the participants. All ethical guidelines were followed as required for conducting human research. The procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional research, the study being approved to be run by the manager of the Izmir Katip Celebi University, where the study was conducted and by the Committee for Ethical Research of Izmir Katip Celebi University (Ethical approval number 307/2016). The research complies with the provisions of the Declaration of Helsinki. All the participants gave their informed consent for the research, and their anonymity was preserved.
Consent for publication
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Beckmann, Y., Türe, S. & Duman, S.U. Vitamin D deficiency and its association with fatigue and quality of life in multiple sclerosis patients. EPMA Journal 11, 65–72 (2020). https://doi.org/10.1007/s13167-019-00191-0
- preventive personalized medicine
- multiple sclerosis
- vitamin D
- health-related quality of life