Clinical Aspects of Vitamin D Deficiency in Multiple Sclerosis

Year 2020, Volume: 2 Issue: 4, 105 - 112, 29.10.2020

Elif Nalan Tolgay Meral Seferoglu , Özlem Taşkapılıoğlu Ömer Faruk Turan

https://doi.org/10.46310/tjim.771364

Abstract

Introduction:
Multiple Sclerosis (MS) is a multifactorial, immune-mediated disorder that occurs in genetically predisposed people. Vitamin D might be an important environmental factor in the development and prevention of MS disease. We aimed to investigate the role of vitamin D in MS disease activity.

Material and Methods:
The study was designed as a prospective study. Thirty-two patients and 15 healthy subjects were included. Variables were MS disease duration, number of relapses, Expanded Disability Status Scale (EDSS) scores, serum vitamin D levels, assessments through neuropsychological tests relevant to depression, cognition, anxiety and fatigue.

Results:
The mean age of the subjects was 32.6±6.9 years. A significant positive correlation was found between the vitamin D level during relapse and remission. A statistically significant difference was found between the patients in relapse and controls in serum vitamin D levels (p=0.002). A statistically significant difference was found between the patients in relapse and patients in remission, in serum vitamin D concentrations (p<0.001). Statistically significant differences were found between the patients in relapse and controls in MMSE, Beck Depression Inventory, Benedict's Cognition Test, Fatigue Severity Scale, PASAT, State-Trait Anxiety Inventory scores (p=0.01, p<0.001, p=0.01, p<0.001, p=0.007, p<0.001 and p<0.001, respectively).

Conclusion:
Vitamin D in association with other therapies may prevent the progression of MS-related disabilities and the relapses in RRMS. Vitamin D levels may have effects on the symptoms (depression, anxiety, cognitive deterioration, and fatigue) which are frequently seen in the course of MS.

Keywords

Multiple Sclerosis, Vitamin D, Cognition,, Disability, Psychiatric comorbidity

References

• 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. 2008 Nov;14(9):1220-4. doi: 10.1177/1352458508094399.
• Soilu-Hänninen M, Laaksonen M, Laitinen I, Erälinna JP, Lilius EM, Mononen I. 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. 2008 Feb;79(2):152-7. doi: 10.1136/jnnp.2006.105320.
• Cantorna MT. Vitamin D and multiple sclerosis: an update. Nutr Rev. 2008 Oct;66(10 Suppl 2):S135-8. doi: 10.1111/j.1753-4887.2008.00097.x.
• Jameson JL, Weetman AP. Tiroid bezi hastalıkları. In: Braunwald E, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL, eds. Çeviri editörü: Sağlıker Y. Harrison İç Hastalıkları Prensipleri. 15th ed. Istanbul: Nobel Matbaacılık; 2004:2060-75.
• Soilu-Hänninen M, Airas L, Mononen I, Heikkilä A, Viljanen M, Hänninen A. 25-Hydroxyvitamin D levels in serum at the onset of multiple sclerosis. Mult Scler. 2005 Jun;11(3):266-71. doi: 10.1191/1352458505ms1157oa.
• Smolders J. Vitamin D and multiple sclerosis: correlation, causality, and controversy. Autoimmune Dis. 2010 Oct 5;2011:629538. doi: 10.4061/2011/629538.
• Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD, Montalban X, O'Connor P, Sandberg-Wollheim M, Thompson AJ, Waubant E, Weinshenker B, Wolinsky JS. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011 Feb;69(2):292-302. doi: 10.1002/ana.22366.
• Armutlu K, Korkmaz NC, Keser I, Sumbuloglu V, Akbiyik DI, Guney Z, Karabudak R. The validity and reliability of the Fatigue Severity Scale in Turkish multiple sclerosis patients. Int J Rehabil Res. 2007 Mar;30(1):81-5. doi: 10.1097/MRR.0b013e3280146ec4.
• Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol. 1989 Oct;46(10):1121-3. doi: 10.1001/archneur.1989.00520460115022.
• Lezak MD. Memory I: Tests. In: Lezak MD, ed. Neuropsychological Assessment. 3rd ed. New York, NY: Oxford University Press; 1995:429-98.
• Forn C, Belenguer A, Belloch V, Sanjuan A, Parcet MA, Avila C. Anatomical and functional differences between the Paced Auditory Serial Addition Test and the Symbol Digit Modalities Test. J Clin Exp Neuropsychol. 2011 Jan;33(1):42-50. doi: 10.1080/13803395.2010.481620.
• Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry. 1961 Jun;4:561-71. doi: 10.1001/archpsyc.1961.01710120031004.
• Aydemir Ö, Köroğlu E. Psikiyatride kullanılan klinik ölçekler. Hekimler Yayın Birliği. 2006;121-291.
• Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975 Nov;12(3):189-98. doi: 10.1016/0022-3956(75)90026-6.
• Benedict RH, Munschauer F, Linn R, Miller C, Murphy E, Foley F, Jacobs L. Screening for multiple sclerosis cognitive impairment using a self-administered 15-item questionnaire. Mult Scler. 2003 Feb;9(1):95-101. doi: 10.1191/1352458503ms861oa.
• Peelen E, Knippenberg S, Muris AH, Thewissen M, Smolders J, Tervaert JW, Hupperts R, Damoiseaux J. Effects of vitamin D on the peripheral adaptive immune system: a review. Autoimmun Rev. 2011 Oct;10(12):733-43. doi: 10.1016/j.autrev.2011.05.002.
• Dörr J, Döring A, Paul F. Can we prevent or treat multiple sclerosis by individualised vitamin D supply? EPMA J. 2013 Jan 29;4(1):4. doi: 10.1186/1878-5085-4-4.
• Orbach H, Zandman-Goddard G, Amital H, Barak V, Szekanecz Z, Szucs G, Danko K, Nagy E, Csepany T, Carvalho JF, Doria A, Shoenfeld Y. Novel biomarkers in autoimmune diseases: prolactin, ferritin, vitamin D, and TPA levels in autoimmune diseases. Ann N Y Acad Sci. 2007 Aug;1109:385-400. doi: 10.1196/annals.1398.044.
• Smolders J, Menheere P, Thewissen M, Peelen E, Tervaert JW, Hupperts R, Damoiseaux J. Regulatory T cell function correlates with serum 25-hydroxyvitamin D, but not with 1,25-dihydroxyvitamin D, parathyroid hormone and calcium levels in patients with relapsing remitting multiple sclerosis. J Steroid Biochem Mol Biol. 2010 Jul;121(1-2):243-6. doi: 10.1016/j.jsbmb.2010.03.001.
• van der Mei IA, Ponsonby AL, Dwyer T, Blizzard L, Taylor BV, Kilpatrick T, Butzkueven H, McMichael AJ. Vitamin D levels in people with multiple sclerosis and community controls in Tasmania, Australia. J Neurol. 2007 May;254(5):581-90. doi: 10.1007/s00415-006-0315-8.
• Simpson S Jr, Taylor B, Blizzard L, Ponsonby AL, Pittas F, Tremlett H, Dwyer T, Gies P, van der Mei I. Higher 25-hydroxyvitamin D is associated with lower relapse risk in multiple sclerosis. Ann Neurol. 2010 Aug;68(2):193-203. doi: 10.1002/ana.22043.
• Pierrot-Deseilligny C, Souberbielle JC. Widespread vitamin D insufficiency: A new challenge for primary prevention, with particular reference to multiple sclerosis. Presse Med. 2011 Apr;40(4 Pt 1):349-56. doi: 10.1016/j.lpm.2011.01.003.
• Jagannath VA, Filippini G, Di Pietrantonj C, Asokan GV, Robak EW, Whamond L, Robinson SA. Vitamin D for the management of multiple sclerosis. Cochrane Database Syst Rev. 2018 Sep 24;9(9):CD008422. doi: 10.1002/14651858.CD008422.pub3.
• Hanwell HE, Banwell B. Assessment of evidence for a protective role of vitamin D in multiple sclerosis. Biochim Biophys Acta. 2011 Feb;1812(2):202-12. doi: 10.1016/j.bbadis.2010.07.017.
• Burton JM, Kimball S, Vieth R, Bar-Or A, Dosch HM, Cheung R, Gagne D, D'Souza C, Ursell M, O'Connor P. A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis. Neurology. 2010 Jun 8;74(23):1852-9. doi: 10.1212/WNL.0b013e3181e1cec2.
• Smolders J, Hupperts R, Barkhof F, Grimaldi LM, Holmoy T, Killestein J, Rieckmann P, Schluep M, Vieth R, Hostalek U, Ghazi-Visser L, Beelke M; SOLAR study group. Efficacy of vitamin D3 as add-on therapy in patients with relapsing-remitting multiple sclerosis receiving subcutaneous interferon β-1a: a Phase II, multicenter, double-blind, randomized, placebo-controlled trial. J Neurol Sci. 2011 Dec 15;311(1-2):44-9. doi: 10.1016/j.jns.2011.04.013.
• Kimball SM, Ursell MR, O'Connor P, Vieth R. Safety of vitamin D3 in adults with multiple sclerosis. Am J Clin Nutr. 2007 Sep;86(3):645-51. doi: 10.1093/ajcn/86.3.645.
• Bell DS. Protean manifestations of vitamin D deficiency, part 2: deficiency and its association with autoimmune disease, cancer, infection, asthma, dermopathies, insulin resistance, and type 2 diabetes. South Med J. 2011 May;104(5):335-9. doi: 10.1097/01.SMJ.0000397893.94525.0e.
• Kivity S, Agmon-Levin N, Zisappl M, Shapira Y, Nagy EV, Dankó K, Szekanecz Z, Langevitz P, Shoenfeld Y. Vitamin D and autoimmune thyroid diseases. Cell Mol Immunol. 2011 May;8(3):243-7. doi: 10.1038/cmi.2010.73.
• Zhang HL, Wu J. Role of vitamin D in immune responses and autoimmune diseases, with emphasis on its role in multiple sclerosis. Neurosci Bull. 2010 Dec;26(6):445-54. doi: 10.1007/s12264-010-0731-8.
• Smolders J, Damoiseaux J, Menheere P, Hupperts R. Vitamin D as an immune modulator in multiple sclerosis, a review. J Neuroimmunol. 2008 Feb;194(1-2):7-17. doi: 10.1016/j.jneuroim.2007.11.014.
• Tetlow LC, Woolley DE. The effects of 1 alpha,25-dihydroxyvitamin D(3) on matrix metalloproteinase and prostaglandin E(2) production by cells of the rheumatoid lesion. Arthritis Res. 1999;1(1):63-70. doi: 10.1186/ar12.
• Gezen-Ak D, Dursun E, Yilmazer S. The effects of vitamin D receptor silencing on the expression of LVSCC-A1C and LVSCC-A1D and the release of NGF in cortical neurons. PLoS One. 2011 Mar 3;6(3):e17553. doi: 10.1371/journal.pone.0017553.
• Buell JS, Tucker KL. The value of physiologic vitamin D as a biomarker of dementia. Drugs Today (Barc). 2011 Mar;47(3):223-31. doi: 10.1358/dot.2011.47.3.1517492.
• Kesby JP, Eyles DW, Burne TH, McGrath JJ. The effects of vitamin D on brain development and adult brain function. Mol Cell Endocrinol. 2011 Dec 5;347(1-2):121-7. doi: 10.1016/j.mce.2011.05.014.
• Nimitphong H, Holick MF. Vitamin D, neurocognitive functioning and immunocompetence. Curr Opin Clin Nutr Metab Care. 2011 Jan;14(1):7-14. doi: 10.1097/MCO.0b013e3283414c38.
• Howland RH. Vitamin D and depression. J Psychosoc Nurs Ment Health Serv. 2011 Feb;49(2):15-8. doi: 10.3928/02793695-20110111-02.
• Thacher TD, Clarke BL. . Vitamin D insufficiency. Mayo Clin Proc. 2011 Jan;86(1):50-60. doi: 10.4065/mcp.2010.0567.
• Stalpers-Konijnenburg SC, Marijnissen RM, Gaasbeek AB, Oude Voshaar RC. [Can I have some sunshine to cheer me up? vitamin D deficiency and depression in the elderly]. Tijdschr Psychiatr. 2011;53(6):365-70.
• Murphy PK, Mueller M, Hulsey TC, Ebeling MD, Wagner CL. An exploratory study of postpartum depression and vitamin D. J Am Psychiatr Nurses Assoc. 2010 May;16(3):170-7. doi: 10.1177/1078390310370476.
• Molnar E, Gonda X, Rihmer Z, Bagdy G. [Etiopathology and therapy of seasonal affective disorder]. Neuropsychopharmacol Hung. 2010 Dec;12(4):483-94.
• Sanders KM, Stuart AL, Williamson EJ, Jacka FN, Dodd S, Nicholson G, Berk M. Annual high-dose vitamin D3 and mental well-being: randomised controlled trial. Br J Psychiatry. 2011 May;198(5):357-64. doi: 10.1192/bjp.bp.110.087544.
• Zender R, Olshansky E. Women's mental health: depression and anxiety. Nurs Clin North Am. 2009 Sep;44(3):355-64. doi: 10.1016/j.cnur.2009.06.002.
• Armstrong DJ, Meenagh GK, Bickle I, Lee AS, Curran ES, Finch MB. Vitamin D deficiency is associated with anxiety and depression in fibromyalgia. Clin Rheumatol. 2007 Apr;26(4):551-4. doi: 10.1007/s10067-006-0348-5.
• Hoeck AD, Pall ML. Will vitamin D supplementation ameliorate diseases characterized by chronic inflammation and fatigue? Med Hypotheses. 2011 Feb;76(2):208-13. doi: 10.1016/j.mehy.2010.09.032.
• Knutsen KV, Brekke M, Gjelstad S, Lagerløv P. Vitamin D status in patients with musculoskeletal pain, fatigue and headache: a cross-sectional descriptive study in a multi-ethnic general practice in Norway. Scand J Prim Health Care. 2010 Sep;28(3):166-71. doi: 10.3109/02813432.2010.505407.
• Berkovitz S, Ambler G, Jenkins M, Thurgood S. Serum 25-hydroxy vitamin D levels in chronic fatigue syndrome: a retrospective survey. Int J Vitam Nutr Res. 2009 Jul;79(4):250-4. doi: 10.1024/0300-9831.79.4.250.
• Knippenberg S, Bol Y, Damoiseaux J, Hupperts R, Smolders J. Vitamin D status in patients with MS is negatively correlated with depression, but not with fatigue. Acta Neurol Scand. 2011 Sep;124(3):171-5. doi: 10.1111/j.1600-0404.2010.01447.x.