Multipl Skleroz ve Vitaminler

Yazarlar

Ali Doğan
https://orcid.org/0000-0003-1796-9451

Özet

Multipl Skleroz (MS) hastalığında vitaminlerin koruyucu ve düzenleyici rolleri, özellikle bağışıklık sistemi fonksiyonları ve sinir hasarının önlenmesi üzerinden ele alınmaktadır. Başta D vitamini olmak üzere, antioksidan özelliklere sahip A, C ve E vitaminlerinin yanı sıra nörotropik etkileri olan B grubu vitaminlerin MS patogenezi ve klinik seyri üzerindeki etkileri kapsamlı bir şekilde incelenmiştir. Mevcut araştırmalar, vitamin takviyelerinin nöroinflamasyonu azaltma, miyelin onarımını destekleme ve yorgunluk gibi semptomları iyileştirme potansiyeline sahip olduğunu vurgulasa da kesin tedavi protokolleri için daha fazla klinik çalışmaya ihtiyaç duyulmaktadır.

 

The roles of vitamins in Multiple Sclerosis (MS) are examined through their protective and regulatory functions, particularly concerning immune system responses and the prevention of nerve damage. The effects of vitamin D, antioxidant vitamins like A, C, and E, and neurotropic B vitamins on the pathogenesis and clinical progression of MS have been extensively reviewed. Current research highlights that vitamin supplementation has the potential to reduce neuroinflammation, support myelin repair, and improve symptoms such as fatigue, although more clinical trials are necessary to establish definitive treatment protocols.

Referanslar

Barnett MH, Parratt JDE, Pollard JD, et al. MS: is it one disease The International MS Journal. 2009; 16:57–65.

Anderson JM, Hampton DW, Patani R, et al. Abnormally phosphorylated tau is associated with neuronal and axonal loss in experimental autoimmune encephalomyelitis and multiple sclerosis. Brain. 2008; 131:1736–48.

Koch M, Mostert J, Heersema D, et al. Progression in multiple sclerosis: further evidence of an age dependent process. Journal Of the Neurological Sciences. 2007; 255:35–41.

Ramagopalan SV, Heger A, Berlanga AJ, et al. A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution. Genome Research, 2010; 20(10):1352–60.

Consortium IMSG. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nature Genetics. 2013; 45(11):1353–60.

Khosravi-Largani M., Pourvali-Talatappeh P., Rousta A.M., et al. A review on potential roles of vitamins in incidence, progression, and improvement of multiple sclerosis. eNeurologicalsci. 2018; 10:37–44. doi: 10.1016/j.ensci.2018.01.007.

M. Adamczyk-Sowa, S. Galiniak, E. Żyracka et al., Oxidative modification of blood serum proteins in multiple sclerosis after interferon beta and melatonin treatment, Oxidative Medicine and Cellular Longevity, 2017; vol. 2017, 8 pages.

M. Sadeghian, V. Mastrolia, A. Rezaei Haddad et al., Mitochondrial dysfunction is an important cause of neurological deficits in an inflammatory model of multiple sclerosis, Scientific Reports, 2016; vol. 6, no. 1.

D. J. Mahad, I. Ziabreva, G. Campbell et al., Mitochondrial changes within axons in multiple sclerosis. Brain: A Journal of Neurology, 2009; vol. 132, no. 5, pp. 1161–1174

L. Haider, M. T. Fischer, J. M. Frischer et al., “Oxidative damage in multiple sclerosis lesions,” Brain: A Journal of Neurology, 2011; vol. 134, no. 7, pp. 1914–1924,

I. Nikić, D. Merkler, C. Sorbara et al., A reversible form of axon damage in experimental autoimmune encephalomyelitis and multiple sclerosis. Nature Medicine, 2011; vol. 17, no. 4, pp. 495–499,

A. Bitsch, J. Schuchardt, S. Bunkowski, T. et al. Acute axonal injury in multiple sclerosis. Correlation with demyelination and inflammation. Brain. 2000; 123, no. 6, pp. 1174–1183.

J. van Horssen, G. Schreibelt, J. Drexhage et al., Severe oxidative damage in multiple sclerosis lesions coincides with enhanced antioxidant enzyme expression. Free Radical Biology & Medicine. 2008; vol. 45, no. 12, pp. 1729–1737.

A. A. Mossakowski, J. Pohlan, D. Bremer et al., Tracking CNS and systemic sources of oxidative stress during the course of chronic neuroinflammation. Acta Neuropathologica. 2015; vol. 130, no. 6, pp. 799–814.

L. Haider, Inflammation, iron, energy failure, and oxidative stress in the pathogenesis of multiple sclerosis. Oxidative Medicine and Cellular Longevity. vol. 2015, 10 pages, 2015.

V. H. Perry, J. A. R. Nicoll, and C. Holmes, Microglia in neurodegenerative disease. Nature Reviews. Neurology. 2010; 6(4),193–201.

Smolders J, Damoiseaux J, Menheere P, et al. Vitamin D as an immune modulator in multiple sclerosis, a review. Journal of Neuroimmunology. 2008; 194:7–17.

Goldberg P. Multiple sclerosis: vitamin D and calcium as environmental determinants of prevalence: (A viewpoint) part 2. biochemical and genetic factors. Journal of Environmental Studies. 1974;6(2–3):121–9.

Munger KL, Levin LI, Hollis BW, et al. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 2006;296(23):2832–8.

Munger KL, Zhang S, O’reilly E, et al. Vitamin D intake and incidence of multiple sclerosis. Neurology. 2004;62(1):60–5.

Salzer J, Hallmans G, Nyström M, et al. Vitamin D as a protective factor in multiple sclerosis. Neurology. 2012;79(21):2140–5.

McLaughlin L, Clarke L, Khalilidehkordi E, et al. Vitamin D for the treatment of multiple sclerosis: a meta-analysis. Journal of Neuroimmunology. 2018; 265:2893–905.

Ascherio A, Munger KL, Simon KC. Vitamin D and multiple sclerosis. Lancet Neurology 2010;9(6):599–612.

Weinstock-Guttman B, Zivadinov R, Qu J, et al. Vitamin D metabolites are associated with clinical and MRI outcomes in multiple sclerosis patients. Journal of Neurology, Neurosurgery and Psychiatry. 2011;82(2):189–95.

Smolders J, Menheere P, Kessels A et al. Association of vitamin D metabolite levels with relapse rate and disability in multiple sclerosis. Multiple Sclerosis. 2008;14(9):1220–4.

Martinelli V, Dalla Costa G, Colombo B, et al. Vitamin D levels and risk of multiple sclerosis in patients with clinically isolated syndromes. Multiple Sclerosis Journal. 2014;20(2):147–55.

Ascherio A, Munger KL, White R, et al. Vitamin D as an early predictor of multiple sclerosis activity and progression. JAMA Neurology. 2014;71(3):306–14.

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.

Mirzaei F, Michels KB, Munger K, et al. Gestational vitamin D and the risk of multiple sclerosis in offspring. Annals of Neurology. 2011;70(1):30–40.

Willer CJ, Dyment DA, Sadovnick AD, et al. Timing of birth and risk of multiple sclerosis: population-based study. British Medical Journal. 2005;330(7483):120.

Staples J, Ponsonby A-L, Lim L. Low maternal exposure to ultraviolet radiation in pregnancy, month of birth, and risk of multiple sclerosis in offspring: longitudinal analysis. British Medical Journal 2010;340:c1640.

Kivity S, Agmon-Levin N, Zisappl M, et al. Vitamin D and autoimmune thyroid diseases. Cellular & Molecular Immunology. 2011;8(3):243–7.

Rajakumar K, Fernstrom JD, Holick MF, et al. Vitamin D status and response to vitamin D3 in obese vs. nonobese African American children. Obesity. 2008;16(1):90–5.

Kimball SM, Ursell MR, O’Connor P, et al. Safety of vitamin D3 in adults with multiple sclerosis. The American Journal of Clinical Nutrition. 2007;86(3):645–51.

Wingerchuk DM, Lesaux J, Rice G, Kremenchutzky M, et al. 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.

Cantorna MT, Hayes CE, DeLuca HF. 1, 25-Dihydroxyvitamin D3 reversibly blocks the progression of relapsing encephalomyelitis, a model of multiple sclerosis. Proceedings of the National Academy of Sciences. 1996;93(15):7861–4.

Spach KM, Hayes CE. Vitamin D3 confers protection from autoimmune encephalomyelitis only in female mice. Journal of Immunology. 2005;175(6):4119–26.

Pedersen LB, Nashold FE, Spach KM, et al. 1, 25-dihydroxyvitamin D3 reverses experimental autoimmune encephalomyelitis by inhibiting chemokine synthesis and monocyte trafficking. Journal of Neurosciences Research. 2007;85(11):2480–90.

Cocco E, Meloni A, Murru MR, et al. Vitamin D responsive elements within the HLA-DRB1 promoter region in Sardinian multiple sclerosis associated alleles. PLoS ONE 2012;7(7): e41678.

Lu M, Taylor B, Körner H. Genomic effects of the vitamin D receptor: potentially the link between vitamin D, immune cells, and multiple sclerosis. Frontiers Immunology. 2018; 9:477.

Haussler MR, Jurutka PW, Mizwicki M, et al. Vitamin D receptor (VDR)-mediated actions of 1α,25(OH)2vitamin D3: Genomic and non-genomic mechanisms. Best Practice & Research Clinical Endocrinology & Metabolism. 2011;25(4):543–59.

Disanto G, Sandve GK, Berlanga-Taylor AJ, et al. Vitamin D receptor binding, chromatin states and association with multiple sclerosis. Human Molecular Genetics. 2012;21(16):3575–86.

Ramagopalan SV, Heger A, Berlanga AJ, et al. A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution. Genome Research. 2010;20(10):1352–60.

Consortium IMSG. 2 WTCCC. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature. 2011;476(7359):214–9.

Smolders J, Peelen E, Thewissen M, et al. The relevance of vitamin D receptor gene polymorphisms for vitamin D research in multiple sclerosis. Autoimmunity Reviews. 2009;8(7):621–6.

Berlanga-Taylor AJ, Disanto G, Ebers GC, et al. Vitamin D–gene interactions in multiple sclerosis. Journal of the Neurological Sciences. 2011;311(1):32–6.

Huang J, Xie Z-F. Polymorphisms in the vitamin D receptor gene and multiple sclerosis risk: a meta-analysis of case–control studies. Journal of the Neurological Sciences. 2012;313(1):79–85.

Rigby W, Waugh M, Graziano R. Regulation of human monocyte HLA-DR and CD4 antigen expression, and antigen presentation by 1, 25-dihydroxyvitamin D3. Blood. 1990;76(1):189–97.

Ramagopalan SV, Maugeri NJ, Handunnetthi L, et al. Expression of the multiple sclerosis- associated MHC class II Allele HLA-DRB1* 1501 is regulated by vitamin D. PLoS Genetics. 2009;5(2):e1000369.

Nolan D, Castley A, Tschochner M, et al. Contributions of vitamin D response elements and HLA promoters to multiple sclerosis risk. Neurology, 2012;79(6):538–46.

Niino M, Fukazawa T, Yabe I, et al. Vitamin D receptor gene polymorphism in multiple sclerosis and the association with HLA class II alleles. Journal of the Neurological Sciences. 2000;177(1):65–71.

Chao MJ, Barnardo MC, Lincoln MR, Ramagopalan SV, et al. HLA class I alleles tag HLA-DRB1* 1501 haplotypes for differential risk in multiple sclerosis susceptibility. Proceedings of the National Academy of Sciences. 2008;105(35):13069–74.

Consortium IMSG. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nature Genetics. 2013;45(11):1353–60.

Cox MB, Ban M, Bowden NA, et al. Potential association of vitamin D receptor polymorphism Taq1 with multiple sclerosis. Multiple Sclerosis Journal. 2012;18(1):16–22.

Orton S-M, Morris AP, Herrera BM, et al. Evidence for genetic regulation of vitamin D status in twins with multiple sclerosis. The American Journal of Clinical Nutrition. 2008;88(2):441–7.

Lin R, Taylor BV, Simpson S, et al. Novel modulating effects of PKC family genes on the relationship between serum vitamin D and relapse in multiple sclerosis. Journal of Neurology, Neurosurgery and Psychiatry. 2014;85(4):399–404.

Gross C, Krishnan AV, Malloy PJ, et al. The vitamin D receptor gene start codon polymorphism: a functional analysis of FokI variants. Journal of Bone and Mineral Metabolism. 1998;13(11):1691–9.

Henry HL. Regulation of vitamin D metabolism. Best Practice & Research Clinical Endocrinology & Metabolism. 2011;25(4):531–41.

Ramagopalan SV, Dyment DA, Cader MZ, et al. Rare variants in the CYP27B1 gene are associated with multiple sclerosis. Annals of Neurology. 2011;70(6):881–6.

Ebers G, Ramagopalan S, Dyment D, et al. Rare variants in the CYP27B1 gene are associated with multiple sclerosis. Journal of Neurology Neurosurgery Psychiatry 2012;83(Suppl 2): A35.

Barizzone N, Pauwels I, Luciano B, et al. No evidence for a role of rare CYP27B1 functional variations in multiple sclerosis. Annals Neurology. 2013;73(3):433–7.

Reinthaler E, Machetanz G, Hotzy C, et al. No evidence for a role of rare CYP27B1 variants in Austrian multiple sclerosis patients. Multiple Sclerosis Journal. 2013; http://dx.doi.org/10.1177/1352458513498130.

Handel AE, Sandve GK, Disanto G, et al. Vitamin D receptor ChIP-seq in primary CD4+ cells: relationship to serum 25-hydroxyvitamin D levels and autoimmune disease. BMC Medicine. 2013;11(1):1–11.

Berge T, Leikfoss I, Brorson I, et al. The multiple sclerosis susceptibility genes TAGAP and IL2RA are regulated by vitamin D in CD4+ T cells. Genes & Immunity. 2016; 25(4):531–41.

Provvedini D, Tsoukas C, Deftos L, et al. 1, 25-dihydroxyvitamin D3 receptors in human leukocytes. Science. 1983;221(4616):1181–3.

Veldman CM, Cantorna MT, DeLuca HF. Expression of 1,25-dihydroxyvitamin D3 receptor in the immune system. Archives of Biochemistry and Biophysics. 2000;374(2):334–8.

Baeke F, Takiishi T, Korf H, et al. Vitamin D. modulator of the immune system. Current Opinion in Pharmacology. 2010;10(4):482–96.

Adams JS, Hewison M. Unexpected actions of vitamin D: new perspectives on the regulation of innate and adaptive immunity. Nature Clinical Practice Nephrology. 2008;4(2):80–90.

Saccone D, Asani F, Bornman L. Regulation of the vitamin D receptor gene by environment, genetics, and epigenetics. Genetics. 2015;561(2):171–80.

von Essen MR, Kongsbak M, Schjerling P, et al. Vitamin D Controls T cell antigen receptor signaling and activation of human T cells. Nature Immunology. 2010;11(4):344–9.

Hayes CE, Hubler SL, Moore JR, et al. Vitamin D actions on CD4(+) T cells in autoimmune disease. Frontier Immunology. 2015; 6:100.

Hayes CE, Acheson ED. A unifying multiple sclerosis etiology linking virus infection, sunlight, and vitamin D, through viral interleukin-10. Medical Hypotheses. 2008;71(1):85–90.

Mayne CG, Spanier JA, Relland LM, et al. 1, 25-Dihydroxyvitamin D3 acts directly on the T lymphocyte vitamin D receptor to inhibit experimental autoimmune encephalomyelitis. European Journal of Immunology. 2011;41(3):822–32.

Correale J, Ysrraelit MC, Gaitán MI Immunomodulatory effects of Vitamin D in multiple sclerosis. Brain. 2009: 3-3.

Smolders J, Thewissen M, Peelen E, et al. Vitamin D status is positively correlated with regulatory T cell function in patients with multiple sclerosis. PLoS ONE 2009;4(8): e6635.

Adorini L. Penna G. Control of autoimmune diseases by the vitamin D endocrine system. Nature Clinical Practice Rheumatology. 2008;4(8):404–12.

Tiosano D, Wildbaum G, Gepstein V, et al. The role of Vitamin D receptor in innate and adaptive immunity: A study in hereditary Vitamin D–resistant rickets patients. The Journal of Clinical Endocrinology & Metabolism. 2013;98(4):1685–93.

Satoh J-I, Tabunoki H. Molecular network of chromatin immunoprecipitation followed by deep sequencing-based vitamin D receptor target genes. Multiple Sclerosis Journal. 2013;19(8):1035–45.

Liu PT, Stenger S, Li H, Wenzel L, et al. Tolllike receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006;311(5768):1770–3.

Zwart SR, Mehta SK, Ploutz-Snyder R, et al. Response to vitamin D supplementation during Antarctic winter is related to BMI, and supplementation can mitigate Epstein–Barr virus reactivation. The Journal of Nutrition. 2011;141(4):692–7.

Lossius A, Vartdal F, Holmøy T. Vitamin D sensitive EBNA-1 specific T cells in the cerebrospinal fluid of patients with multiple sclerosis. Journal of Neuroimmunology. 2011; 240:87–96.

Correale J, Gaitan M. Multiple sclerosis and environmental factors: the role of vitamin D, parasites, and Epstein–Barr virus infection. Acta Neurologica Scandinavica. 2015;132(S199):46–55.

Ramien C, Pachnio A, Sisay S, et al. Hypovitaminosis-D and EBV: no interdependence between two MS risk factors in a healthy young UK autumn cohort. Multiple Sclerosis Journal. 2014;20(6):751–3.

Disanto G, Handel AE, Damoiseaux J, et al. Vitamin D supplementation and antibodies against the Epstein–Barr virus in multiple sclerosis patients. Multiple Sclerosis Journal. 2013. http://dx.doi.org/10.1177/1352458513494494.

Salzer J, Nyström M, Hallmans G, et al. Epstein–Barr virus antibodies and vitamin D in prospective multiple sclerosis biobank samples. Multiple Sclerosis Journal. 2013;19(12):1587–91.

Disanto G, Meier U, Giovannoni G, et al. Vitamin D: a link between Epstein–Barr virus and multiple sclerosis development? Expert Review of Neurotherapeutics. 2011;11(9):1221–4.

Munger K, Ascherio A. Understanding the joint effects of EBV and vitamin D in MS. Multiple Sclerosis Journal. 2013;19(12):1554–5.

Holmøy T. Vitamin D status modulates the immune response to Epstein–Barr virus: Synergistic effect of risk factors in multiple sclerosis. Medical Hypotheses. 2008;70(1):66–9.

Martinez-Forero I, Garcia-Munoz R, Martinez-Pasamar S, et al. IL-10 suppressor activity and ex vivo Tr1 cell function are impaired in multiple sclerosis. European Journal of Immunology. 2008;38(2):576–86.

Özenci V, Kouwenhoven M, Huang YM, et al. Multiple sclerosis is associated with an imbalance between tumour necrosis factor-alpha (TNF-α)-and IL-10-secreting blood cells that is corrected by interferon-beta (IFN-β) treatment. Clinical & Experimental Immunology. 2000;120(1):147–53.

Vandenbark AA, Finn T, Barnes D, et al. Diminished frequency of interleukin-10-secreting, T-cell receptor peptide-reactive T cells in multiple sclerosis patients might allow expansion of activated memory T cells bearing the cognate BV gene. Journal of Neuroscience Research. 2001;66(2):171–6.

Spach KM, Nashold FE, Dittel BN, et al. IL-10 signaling is essential for 1, 25-dihydroxyvitamin D3-mediated inhibition of experimental autoimmune encephalomyelitis. The Journal of Immunology. 2006;177(9):6030–7.

Bender DA. B vitamins in the nervous system. In: NN Osborne, eds. Selected Topics from Neurochemistry. 1985: 397- 423.

Kennedy D. B vitamins and the brain: mechanisms, dose, and efficacy—a review. Nutrients. 2016; 8(2): 68.

Zempleni J, Suttie JW, Gregory JF III, Stover PJ. Handbook of Vitamins. Boca Raton, Florida, USA: CRC Press; 2013.

Shideler C. Vitamin B6: an overview. American Journal of Medical Technology. 1983; 49(1): 17- 22.

Sechi G, Sechi E, Fois C, et al. Advances in clinical determinants and neurological manifestations of B vitamin deficiency in adults. Nutrition Reviews. 2016; 74(5): 281- 300.

Geller M, Oliveira L, Nigri R, et al. Vitamins and Minerals. 2017.

Isenberg-Grzeda E, Kutner HE, Nicolson SE. Wernicke-Korsakoff-syndrome: under-recognized and under-treated. Psychosomatics. 2012; 53(6): 507- 516.

Costantini A, Nappo A, Pala MI, et al. High dose thiamine improves fatigue in multiple sclerosis. BMJ Case Reports. 2013.doi:10.1136/bcr-2013-009144

Mikkelsen K, Stojanovska L, Tangalakis K, Bosevski M, Apostolopoulos V. Cognitive decline: a vitamin B perspective. Maturitas. 2016; 93: 108- 113.

Martin P. Molecular mechanisms of thiamine utilization. Current Molecular Medicine. 2001;1(2):197-207.

Johnson WD, Storts RW. Peripheral neuropathy associated with dietary riboflavin deficiency in the chicken, I: light microscopic study. Veterinary Pathology. 1988; 25(1):9-16.

Naghashpour M, Amani R, Sarkaki A, et al. Brain-derived neurotrophic and immunologic factors: beneficial effects of riboflavin on motor disability in murine model of multiple sclerosis. Iranian Journal of Basic Medical Sciences. 2016;19(4):439-448.

Naghashpour M, Majdinasab N, Shakerinejad G, et al. Riboflavin supplementation to patients with multiple sclerosis does not improve disability status nor is riboflavin supplementation correlated to homocysteine. International Journal for Vitamin and Nutrition Research. 2013;83(5): 281-290

Graf, J., Leussink, V. I., Dehmel, T., et al. Infectious risk stratification in multiple sclerosis patients receiving immunotherapy. Annals of clinical and translational neurology., 2017; 4(12), 909-91

F. Sedel, D. Bernard, D. M. Mock et al. Targeting demyelination and virtual hypoxia with high-dose biotin as a treatment for progressive multiple sclerosis. Neuropharmacology. 2016; 110, 644–653.

F. Sedel, C. Papeix, A. B ellanger, et al. High doses of biotin in chronic progressive multiple sclerosis. Multiple Sclerosis and Related Disorders. 2015; 4, 159–169.

A. Tourbah, C. L ebrun-F renay, et al. MD1003 (high-dose biotin) for the treatment of progressive multiple sclerosis: A randomised, double-blind, placebo-controlled study. Multiple Sclerosis Journal. 2016; 22, 1719–1731.

Solomon LR. Cobalamin-responsive disorders in the ambulatory care setting: unreliability of cobalamin, methylmalonic acid, and homocysteine testing. Blood. 2005;105(3):978-985

Reynolds EH, Linnell JC, Faludy JE. Multiple sclerosis associated with vitamin B12 deficiency. Journal of Neuroimmunology. 1991; 48:808–11.

Miller A, Korem M, Almog R, et al. Vitamin B12, demyelination, remyelination and repair in multiple sclerosis. Journal of the Neurological Sciences.2005;93–7.

Wade DT, Young CA, Chaudhuri KR, et al. A Randomized placebo controlled exploratory study of vitamin B-12, lofepramine, and L-phenylalanine (the “Cari Loder regime”) in the treatment of multiple sclerosis. Journal of Neurology, Neurosurgery and Psychiatry. 2002; 73:246–9.

Reynolds EH. Multiple sclerosis and vitamin B12 metabolism. Journal of Neuroimmunology. 1992:225–30.

Nijist TQ, Wevers RA, Schoonderwaldt HC, et al. Vitamin B12 and folate concentrations in serum and cerebrospinal fluid of neurological patients with special reference to multiple sclerosis and dementia. Journal of Neurology, Neurosurgery and Psychiatry. 1990; 53:951–4.

Vrethem M, Mattsson E, Hebelka H, et al. Increased plasma homocysteine levels without signs of vitamin B12 deficiency in patients with multiple sclerosis assessed by blood and fluid homocysteine and methylmalonic acid. Multiple Sclerosis.2003; 9:239–45.

Kira J, Tobimatsu S, Goto J. Vitamin B12 metabolism and massivedose methyl vitamin B12 therapy in Japanese patients with multiple sclerosis. Internal Medicine.1994; 33:82–6.

Besler H. T., Çomoğlu S. Ç., Okçu Z. İ., “Serum levels of antioxidant vitamins and lipid peroxidation in multiple sclerosis,” Nutritional Neuroscience. 2013;5(3),215–220.

Vladutiu A, Cringulescu N. Suppression of experimental allergic encephalomyelitis by vitamin A. Experientia. 1968;24(7):718-719.

Mohammadzadeh Honarvar N, Harirchian MH, Abdolahi M, et al. Retinyl palmitate supplementation modulates t-bet and interferon gamma gene expression in multiple sclerosis patients. Journal of Molecular Neuroscience. 2016;59(3):360-365.

Raverdeau M., Breen C. J., A. Misiak, K. H. G. Mills. Retinoic acid suppresses IL-17 production and pathogenic activity of γδ T cells in CNS autoimmunity. Immunology and Cell Biology. 2016; 94(8),763–773.

Bitarafan S, Saboor-Yaraghi A, Sahraian M-A, et al. Effect of vitamin A supplementation on fatigue and depression in multiple sclerosis patients: a double-blind placebo-controlled clinical trial. Iran J Allergy Asthma Immunology. 2016;15(1):13-19.

A. Carr and B. Frei. Does vitamin C act as a pro-oxidant under physiological conditions? FASEB Journal. 1999;13(9),1007–1024.

Y.-e. Guo, N. Suo, X. Cui, et al. Vitamin C promotes oligodendrocytes generation and remyelination. Glia. 2018; 66(7), 1302–1316.

Spitsin SV, Scott GS, Mikheeva T, et al. Comparison of uric acid and ascorbic acid in protection against EAE. Free Radical Biological Medicine. 2002; 33(10):1363-1371.

Besler HT, Comoğlu S, Okçu Z. Serum levels of antioxidant vitamins and lipid peroxidation in multiple sclerosis. Nutritional Neuroscience. 2002;5(3):215-220.

Burton, G.W. Vitamin E: Molecular and biological function. Proceedings of the Nutrition Society. 1994; 53, 251–262.

Southam, E. Thomas, P.K. et al. Experimental vitamin e deficiency in rats: Morphological and functional evidence of abnormal axonal transport secondary to free radical damage. Brain. 1991; 114, 915–936.

Urano, S. Asai, Y. Makabe, S. et al. Oxidative injury of synapse and alteration of antioxidative defense systems in rats, and its prevention by vitamin. European Journal of Biochemistry. 1997; 245, 64–70.

Jiang, Q. Natural forms of vitamin E: Metabolism, antioxidant, and anti-inflammatory activities and their role in disease prevention and therapy. Free Radical Biology & Medicine. 2014, 72, 76–90.

Xue H, Ren H, Zhang L, et al. Alpha tocopherol ameliorates experimental autoimmune encephalomyelitis through the regulation of Th1 cells. Iranian Journal of Basic Medical Sciences 2016;19(5):561-566.

Blanchard B, Heurtaux T, Garcia C, et al. Tocopherol derivative TFA-12 promotes myelin epair in experimental models of multiple sclerosis. Journal of Neuroscience. 2013;33(28):11633-11642.

Goudarzvand M, Javan M, Mirnajafi-Zadeh J, et al. Vitamins E and D3 attenuate demyelination and potentiate remyelination processes of hippocampal formation of rats following local injection of ethidium bromide. Cellular and Molecular Neurobiology. 2010;30(2):289-299

K. I. Løken-Amsrud, K. M. Myhr, S. J. Bakke et al., “Alpha-tocopherol and MRI outcomes in multiple sclerosis--association and prediction,” PloS ONE. 2013. 8(1),54-417.

Li J, Lin JC, Wang H, et al. Novel role of vitamin K in preventing oxidative injury to developing oligodendrocytes and neurons. Journal of Neuroscience. 2003;23(13):581626.

Li J, Wang H, Rosenberg PA. Vitamin K prevents oxidative cell death by inhibiting activation of 12-lipoxygenase in developing oligodendrocytes. Journal of Neuroscience. 2009;87(9):1997–2005.

Fusaro, M. Cianciolo, G. Brandi, et al. Vitamin K and Osteoporosis. Nutrients. 2020; 12, 3625.

Lasemi, R.; Kundi, M.; Moghadam, N.B. et al. Vitamin K2 in multiple sclerosis patients. KlinWochenschr. 2018; 130, 307–313.

Sakaue, M. Mori, N. Okazaki, M. et al. Vitamin K has the potential to protect neurons from methylmercury-induced cell death In Vitro. Journal Neuroscience Research. 2011; 89,1052–1058.

Popescu, D.C. Huang, H. Singhal, N.K. et al. Vitamin K enhances the production of brain sulfatides during remyelination. PLoS ONE. 2018; 13.

Goudarzi, S. Rivera, A. Butt, A.M. et al. Gas6 Promotes Oligodendrogenesis and Myelination in the Adult Central Nervous System and After Lysolecithin-Induced Demyelination. ASN Neurology. 2016; 8.

Moriya M, Nakatsuji Y, Okuno T, et al. Vitamin K2 ameliorates experimental autoimmune encephalomyelitis in Lewis rats. Journal of Neuroimmunology. 2005;170(1):11–20.

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