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CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Meta-Analysis

Myasthenia Gravis and Vitamin D Serum Levels: A Systematic Review and Meta-analysis

Author(s): Giovanni Bonaccorso*

Volume 22, Issue 5, 2023

Published on: 05 September, 2022

Page: [752 - 760] Pages: 9

DOI: 10.2174/1871527321666220707111344

open access plus

Abstract

Background: Vitamin D has been extensively studied for its role in immune modulation, especially in the process of tolerance induction. The loss of tolerance towards self-antigens is the basis of several autoimmune disorders; this seems to be related to lower levels of Vitamin D. A neurological autoimmune disorder due to the loss of tolerance to compounds at the neuromuscular junction is known as Myasthenia Gravis (MG).

Objective: To assess the possible correlation between altered Vitamin D levels and MG.

Methods: In this systematic review, all recruited studies compared Vitamin D levels in MG patients and healthy controls. Five studies fulfilled the selection criteria and were included in the quantitative synthesis. The meta-analysis involved data of a total population size of 450 individuals, equally divided into 219 cases and 231 controls.

Results: The results showed a statistically significant mean difference between cases and controls. The overall mean Vitamin D levels in MG patients were 4.69 ng/ml lower than control levels (95% CI -6.17; -3.22); by applying a random-effects model, this mean difference was estimated at -3.79 (95% CI -7.24; -0.33), after exclusion of data source of heterogeneity and through applying a fixed-effect model, resulted in a mean difference -5.39 (95% CI -6.91; -3.88). The p-value was lower than 0.05.

Conclusion: There are statistically significant lower levels of Vitamin D in MG patients, so routine checking and possible correction should be advised in MG patients based on the current data.

Keywords: Myasthenia Gravis, Autoimmunity, Tolerance, Vitamin D, cholecalciferol, 25-hydroxy-cholecalciferol.

Graphical Abstract

[1]
Bubuioc AM, Kudebayeva A, Turuspekova S, Lisnic V, Leone MA. The epidemiology of myasthenia gravis. J Med Life 2021; 14(1): 7-16.
[http://dx.doi.org/10.25122/jml-2020-0145] [PMID: 33767779]
[2]
Dresser L, Wlodarski R, Rezania K, Soliven B. Myasthenia gravis: Epidemiology, pathophysiology and clinical manifestations. J Clin Med 2021; 10(11): 2235.
[http://dx.doi.org/10.3390/jcm10112235] [PMID: 34064035]
[3]
Gilhus NE. Myasthenia gravis. N Engl J Med 2016; 375(26): 2570-81.
[http://dx.doi.org/10.1056/NEJMra1602678] [PMID: 28029925]
[4]
Rodolico C, Nicocia G, Damato V, Antonini G, Liguori R, Evoli A. Benefit and danger from immunotherapy in myasthenia gravis. Neurol Sci 2021; 42(4): 1367-75.
[http://dx.doi.org/10.1007/s10072-021-05077-6] [PMID: 33543421]
[5]
Katz NK, Barohn RJ. The history of acetylcholinesterase inhibitors in the treatment of myasthenia gravis. Neuropharmacology 2021; 182: 108303.
[http://dx.doi.org/10.1016/j.neuropharm.2020.108303] [PMID: 32918950]
[6]
Leopardi V, Chang YM, Pham A, Luo J, Garden OA. A systematic review of the potential implication of infectious agents in myasthenia gravis. Front Neurol 2021; 12: 618021.
[http://dx.doi.org/10.3389/fneur.2021.618021] [PMID: 34194378]
[7]
Huang YT, Chen YP, Lin WC, Su WC, Sun YT. Immune checkpoint inhibitor-induced myasthenia gravis. Front Neurol 2020; 11: 634.
[http://dx.doi.org/10.3389/fneur.2020.00634] [PMID: 32765397]
[8]
Martens PJ, Gysemans C, Verstuyf A, Mathieu AC. Vitamin D’s effect on immune function. Nutrients 2020; 12(5): 1248.
[http://dx.doi.org/10.3390/nu12051248] [PMID: 32353972]
[9]
Ao T, Kikuta J, Ishii M. The effects of vitamin D on immune system and inflammatory diseases. Biomolecules 2021; 11(11): 1624.
[http://dx.doi.org/10.3390/biom11111624] [PMID: 34827621]
[10]
Charoenngam N, Holick MF. Immunologic effects of vitamin d on human health and disease. Nutrients 2020; 12(7): 2097.
[http://dx.doi.org/10.3390/nu12072097] [PMID: 32679784]
[11]
Fritsche J, Mondal K, Ehrnsperger A, Andreesen R, Kreutz M. Regulation of 25-hydroxyvitamin D3-1 α-hydroxylase and production of 1 α25-dihydroxyvitamin D3 by human dendritic cells. Blood 2003; 102(9): 3314-6.
[http://dx.doi.org/10.1182/blood-2002-11-3521] [PMID: 12855575]
[12]
Li CH, Zhang J, Baylink DJ, et al. Dendritic cells, engineered to overexpress 25-hydroxyvitamin D 1α-hydroxylase and pulsed with a myelin antigen, provide myelin-specific suppression of ongoing experimental allergic encephalomyelitis. FASEB J 2017; 31(7): 2996-3006.
[http://dx.doi.org/10.1096/fj.201601243R] [PMID: 28363955]
[13]
Justo ME, Aldecoa M, Cela E, et al. Low vitamin D serum levels in a cohort of myasthenia gravis patients in Argentina. Photochem Photobiol 2021; 97(5): 1145-9.
[http://dx.doi.org/10.1111/php.13432] [PMID: 33866582]
[14]
Askmark H, Haggård L, Nygren I, Punga AR. Vitamin D deficiency in patients with myasthenia gravis and improvement of fatigue after supplementation of vitamin D3: A pilot study. Eur J Neurol 2012; 19(12): 1554-60.
[http://dx.doi.org/10.1111/j.1468-1331.2012.03773.x] [PMID: 22672742]
[15]
Guan Y, Lv F, Meng Y, et al. Association between bone mineral density, muscle strength, and vitamin D status in patients with myasthenia gravis: A cross-sectional study. Osteoporos Int 2017; 28(8): 2383-90.
[http://dx.doi.org/10.1007/s00198-017-4041-0] [PMID: 28439619]
[16]
Kang SY, Kang JH, Choi JC, Song SK, Oh JH. Low serum vitamin D levels in patients with myasthenia gravis. J Clin Neurosci 2018; 50: 294-7.
[http://dx.doi.org/10.1016/j.jocn.2018.01.047] [PMID: 29396067]
[17]
Chroni E, Dimisianos N, Punga AR. Low vitamin D levels in healthy controls and patients with autoimmune neuromuscular disorders in Greece. Acta Neurol Belg 2016; 116(1): 57-63.
[http://dx.doi.org/10.1007/s13760-015-0512-2] [PMID: 26183131]
[18]
Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies in epidemiology: A proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000; 283(15): 2008-12.
[http://dx.doi.org/10.1001/jama.283.15.2008] [PMID: 10789670]
[19]
Shamseer L, Moher D, Clarke M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: Elaboration and explanation. BMJ 2015; 350(jan02 1): g7647.
[http://dx.doi.org/10.1136/bmj.g7647] [PMID: 25555855]
[20]
Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol 2014; 14(1): 135.
[http://dx.doi.org/10.1186/1471-2288-14-135] [PMID: 25524443]
[21]
NIH. Quality assessment of case-control studies https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools
[22]
Sakai T, Shirai T, Oishi T. Vitamins K and D deficiency in severe motor and intellectually disabled patients. Brain Dev 2021; 43(2): 200-7.
[http://dx.doi.org/10.1016/j.braindev.2020.09.011] [PMID: 33139126]
[23]
Sato Y, Oizumi K, Kuno H, Kaji M. Effect of immobilization upon renal synthesis of 1,25-dihydroxyvitamin D in disabled elderly stroke patients. Bone 1999; 24(3): 271-5.
[http://dx.doi.org/10.1016/S8756-3282(98)00185-9] [PMID: 10071922]
[24]
Moradi S, Shahdadian F, Mohammadi H, Rouhani MH. A comparison of the effect of supplementation and sunlight exposure on serum vitamin D and parathyroid hormone: A systematic review and meta-analysis. Crit Rev Food Sci Nutr 2020; 60(11): 1881-9.
[http://dx.doi.org/10.1080/10408398.2019.1611538] [PMID: 31107101]
[25]
Hanel A, Carlberg C. Vitamin D and evolution: Pharmacologic implications. Biochem Pharmacol 2020; 173: 113595.
[http://dx.doi.org/10.1016/j.bcp.2019.07.024] [PMID: 31377232]
[26]
Stewart AF, Adler M, Byers CM, Segre GV, Broadus AE. Calcium homeostasis in immobilization: An example of resorptive hypercalciuria. N Engl J Med 1982; 306(19): 1136-40.
[http://dx.doi.org/10.1056/NEJM198205133061903] [PMID: 6280047]
[27]
Sato Y, Asoh T, Oizumi K. High prevalence of vitamin D deficiency and reduced bone mass in elderly women with Alzheimer’s disease. Bone 1998; 23(6): 555-7.
[http://dx.doi.org/10.1016/S8756-3282(98)00134-3] [PMID: 9855465]
[28]
Hiemstra TF, Casian A, Boraks P, Jayne DR, Schoenmakers I. Plasma exchange induces vitamin D deficiency. QJM 2014; 107(2): 123-30.
[http://dx.doi.org/10.1093/qjmed/hct208] [PMID: 24131546]
[29]
Cadegiani FA. Remission of severe myasthenia gravis after massive-dose vitamin D treatment. Am J Case Rep 2016; 17: 51-4.
[http://dx.doi.org/10.12659/AJCR.894849] [PMID: 26822380]
[30]
Silva LFF, Martins MC, Caplum MC, et al. Myasthenia gravis in pregnancy treated with daily massive vitamin D dose. Asp Biomed Clin Case Rep 2020; 3(2): 171-7.
[http://dx.doi.org/10.36502/2020/ASJBCCR.6208]
[31]
Okparasta A, Indrasyah MI, Haddani H, et al. Effect of vitamin D3 supplementation towards vitamin D serum levels and Myasthenia Gravis Composite Score (MGCS). J Phys Conf Ser 2019; 1246(1): 012032.
[http://dx.doi.org/10.1088/1742-6596/1246/1/012032]
[32]
Lewis SJ, Smith PE. Osteoporosis prevention in myasthenia gravis: A reminder. Acta Neurol Scand 2001; 103(5): 320-2.
[http://dx.doi.org/10.1034/j.1600-0404.2001.103005320.x] [PMID: 11328209]
[33]
Lv F, Guan Y, Ma D, et al. Effects of alendronate and alfacalcidol on bone in patients with myasthenia gravis initiating glucocorticoids treatment. Clin Endocrinol (Oxf) 2018; 88(3): 380-7.
[http://dx.doi.org/10.1111/cen.13537] [PMID: 29266368]

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