Abstract
Background: Despite the vitamin D treatment in patients with multiple sclerosis (MS), there continues to be controversial discrepancy in outcomes according to the current research. Many systematic reviews have evaluated the effect of vitamin D as an adjuvant treatment in patients with MS; however, there is no consensus on the optimum administration time and dosage of vitamin D intake. A meta-analysis for exploring the different administration time and dosage of vitamin D is warranted. Methods: Randomized controlled trials (RCTs) on the effect of different administration time and dosage of vitamin D in patients with MS were recorded within 7 databases. This meta-analysis was performed with 2 clinical outcomes: EDSS (Expanded Disability Status Scale) and relapses during research. Results: The pooled results indicated that receiving different administration time and dosage of vitamin D as an adjuvant treatment had no significant therapeutic effect on MS according to the EDSS scores and relapses during research. Conclusion: According to our meta-analysis, the administration of vitamin D in different dosages (ranging from 2,857 to 14,007 IU/day) and treatment period (ranging from 6 to 24 months) did not affect the clinical outcomes (EDSS and relapses during research) in patients with MS. Additional RCTs should be conducted to explore whether a longer duration and a larger dosage of vitamin D without serious adverse effects might produce therapeutic effects in patients with MS.
References
1.
Thompson
AJ
, Baranzini
SE
, Geurts
J
, Hemmer
B
, Ciccarelli
O
. Multiple sclerosis
. Lancet
. 2018
;391
(10130
):1622
–36
. .2.
Hempel
S
, Graham
GD
, Fu
N
, Estrada
E
, Chen
AY
, Miake-Lye
I
, A systematic review of modifiable risk factors in the progression of multiple sclerosis
. Mult Scler
. 2017
;23
(4
):525
–33
. .3.
Tamblyn
JA
, Hewison
M
, Wagner
CL
, Bulmer
JN
, Kilby
MD
. Immunological role of vitamin D at the maternal-fetal interface
. J Endocrinol
. 2015
;224
(3
):R107
–21
. .4.
Yamout
B
, Sahraian
M
, Bohlega
S
, Al-Jumah
M
, Goueider
R
, Dahdaleh
M
, Consensus recommendations for the diagnosis and treatment of multiple sclerosis: 2019 revisions to the MENACTRIMS guidelines
. Mult Scler Relat Disord
. 2020
;37
:101459
. .5.
Rae-Grant
A
, Day
GS
, Marrie
RA
, Rabinstein
A
, Cree
BAC
, Gronseth
GS
, Practice guideline recommendations summary: Disease-modifying therapies for adults with multiple sclerosis: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology [published covrrection appears in Neurology. 2019 Jan 8;92(2):112]
. Neurology
. 2018
;90
(17
):777
–88
.6.
Goltzman
D
, Mannstadt
M
, Marcocci
C
. Physiology of the calcium-parathyroid hormone-vitamin D axis
. Front Horm Res
. 2018
;50
:1
–13
. .7.
Hayes
CE
, Hubler
SL
, Moore
JR
, Barta
LE
, Praska
CE
, Nashold
FE
. Vitamin D actions on CD4(+) T cells in autoimmune disease
. Front Immunol
. 2015
;6
:100
. Published 2015 Mar 18. .8.
Khosravi-Largani
M
, Pourvali-Talatappeh
P
, Rousta
AM
, Karimi-Kivi
M
, Noroozi
E
, Mahjoob
A
, A review on potential roles of vitamins in incidence, progression, and improvement of multiple sclerosis
. eNeurologicalSci
. 2018
;10
:37
–44
. Published 2018 Jan 28. .9.
Kuhle
J
, Disanto
G
, Dobson
R
, Adiutori
R
, Bianchi
L
, Topping
J
, Conversion from clinically isolated syndrome to multiple sclerosis: a large multicenter study
. Mult Scler
. 2015
;21
(8
):1013
–24
.10.
Hewer
S
, Lucas
R
, van der Mei
I
, Taylor
BV
. Vitamin D and multiple sclerosis
. J Clin Neurosci
. 2013
;20
(5
):634
–41
. .11.
Pierrot-Deseilligny
C
, Rivaud-Péchoux
S
, Clerson
P
, de Paz
R
, Souberbielle
JC
. Relationship between 25-OH-D serum level and relapse rate in multiple sclerosis patients before and after vitamin D supplementation
. Ther Adv Neurol Disord
. 2012
;5
(4
):187
–98
. .12.
Zhen
C
, Feng
X
, Li
Z
, Wang
Y
, Li
B
, Li
L
, Suppression of murine experimental autoimmune encephalomyelitis development by 1,25-dihydroxyvitamin D3 with autophagy modulation
. J Neuroimmunol
. 2015
;280
:1
–7
. .13.
Chiuso-Minicucci
F
, Ishikawa
LL
, Mimura
LA
, Fraga-Silva
TFC
, Donegá França
TG
, Zorzella-Pezavento
SFG
, Treatment with vitamin D/MOG association suppresses experimental autoimmune encephalomyelitis [published correction appears in PLoS One. 2015;10(7):e0131260]
. PLoS One
. 2015
;10
(5
):e0125836
.14.
Dörr
J
, Bäcker-Koduah
P
, Wernecke
KD
, Becker
E
, Hoffmann
F
, Faiss
J
, High-dose vitamin D supplementation in multiple sclerosis – results from the randomized EVIDIMS (efficacy of vitamin D supplementation in multiple sclerosis) trial
. Mult Scler J Exp Transl Clin
. 2020
;6
(1
):2055217320903474
. Published 2020 Jan 24. .15.
Hupperts
R
, Smolders
J
, Vieth
R
, Holmøy
T
, Marhardt
K
, Schluep
M
, Randomized trial of daily high-dose vitamin D3 in patients with RRMS receiving subcutaneous interferon β-1a
. Neurology
. 2019
;93
(20
):e1906
–16
. .16.
Camu
W
, Lehert
P
, Pierrot-Deseilligny
C
, Hautecoeur
P
, Besserve
A
, Jean Deleglise
AS
, Cholecalciferol in relapsing-remitting MS: A randomized clinical trial (CHOLINE) [published correction appears in Neurol Neuroimmunol Neuroinflamm. 2019 Nov 15;7(1):]
. Neurol Neuroimmunol Neuroinflamm
. 2019
;6
(5
):e597
.17.
Soilu-Hänninen
M
, Aivo
J
, Lindström
BM
, Elovaara
I
, Sumelahti
ML
, Färkkilä
M
, A randomised, double blind, placebo controlled trial with vitamin D3 as an add on treatment to interferon β-1b in patients with multiple sclerosis
. J Neurol Neurosurg Psychiatry
. 2012
;83
(5
):565
–71
. .18.
Burton
JM
, Kimball
S
, Vieth
R
, Bar-Or
A
, Dosch
HM
, Cheung
R
, A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis [published correction appears in Neurology. 2010 Aug 3;75(5):480] [published correction appears in Neurology. 2010 Sep 14;75(11):1029. Dosage error in article text]
. Neurology
. 2010
;74
(23
):1852
–9
.19.
Mosayebi
G
, Ghazavi
A
, Ghasami
K
, Jand
Y
, Kokhaei
P
. Therapeutic effect of vitamin D3 in multiple sclerosis patients
. Immunol Invest
. 2011
;40
(6
):627
–39
. .20.
Golan
D
, Halhal
B
, Glass-Marmor
L
, Staun-Ram
E
, Rozenberg
O
, Lavi
I
, 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 Jun 14
;13
:60
. .21.
Kampman
MT
, Steffensen
LH
, Mellgren
SI
, Jørgensen
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
. .22.
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
. Mult Scler Int
. 2012
;2012
:452541
. .23.
Stein
MS
, Liu
Y
, Gray
OM
, Baker
JE
, Kolbe
SC
, Ditchfield
MR
, A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis
. Neurology
. 2011
;77
(17
):1611
–8
. .24.
McLaughlin
L
, Clarke
L
, Khalilidehkordi
E
, Butzkueven
H
, Taylor
B
, Broadley
SA
. Vitamin D for the treatment of multiple sclerosis: a meta-analysis
. J Neurol
. 2018
;265
(12
):2893
–905
. .25.
Doosti-Irani
A
, Tamtaji
OR
, Mansournia
MA
, Ghayour-Mobarhan
M
, Ferns
G
, Daneshvar Kakhaki
R
, The effects of vitamin D supplementation on expanded disability status scale in people with multiple sclerosis: a critical, systematic review and metaanalysis of randomized controlled trials
. Clin Neurol Neurosurg
. 2019
;187
:105564
. .26.
Zheng
C
, He
L
, Liu
L
, Zhu
J
, Jin
T
. The efficacy of vitamin D in multiple sclerosis: a meta-analysis
. Mult Scler Relat Disord
. 2018
;23
:56
–61
. .27.
Martínez-Lapiscina
EH
, Mahatanan
R
, Lee
CH
, Charoenpong
P
, Hong
JP
. Associations of serum 25(OH) vitamin D levels with clinical and radiological outcomes in multiple sclerosis, a systematic review and meta-analysis
. J Neurol Sci
. 2020
;411
:116668
. .28.
McDonald
WI
, Compston
A
, Edan
G
, Goodkin
D
, Hartung
HP
, Lublin
FD
, Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the Diagnosis of Multiple Sclerosis
. Ann Neurol
. 2001
;50
:121
–7
. .29.
Polman
CH
, Reingold
SC
, Edan
G
, Filippi
M
, Hartung
HP
, Kappos
L
, Diagnostic criteria for multiple sclerosis: 2005 revisions to the McDonald Criteria
. Ann Neurol
. 2005
;58
:840
–6
.30.
Kurtzke
JF
. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS)
. Neurology
. 1983
;33
:1444
–52
. .31.
Higgins
JPT
, Thomas
J
, Chandler
J
, Cumpston
M
, Li
T
, Page
MJ
, , editors. Cochrane handbook for systematic reviews of interventions
. 2nd ed. Chichester (UK)
: John Wiley & Sons
; 2019
.32.
McMaster University, Evidence Prime Inc
. GRADEpro GDT
; 2015
. Available from: https://gradepro.org/ (accessed Oct 1, 2019).33.
Feige
J
, Salmhofer
H
, Hecker
C
, Kunz
AB
, Franzen
M
, Moré
E
, Life-threatening vitamin D intoxication due to intake of ultra-high doses in multiple sclerosis: a note of caution
. Mult Scler
. 2019
;25
(9
):1326
–8
. .34.
Ontaneda
D
. Progressive multiple sclerosis
. Continuum
. 2019
;25
(3
):736
–52
. .35.
Findling
O
, Hauer
L
, Pezawas
T
, Rommer
PS
, Struhal
W
, Sellner
J
. Cardiac autonomic dysfunction in multiple sclerosis: a systematic review of current knowledge and impact of immunotherapies
. J Clin Med
. 2020
;9
(2
):335
. Published 2020 Jan 24. .36.
Feige
J
, Moser
T
, Bieler
L
, Schwenker
K
, Hauer
L
, Sellner
J
. Vitamin D supplementation in multiple sclerosis: a critical analysis of potentials and threats
. Nutrients
. 2020
;12
(3
):783
. Published 2020 Mar 16. .© 2021 S. Karger AG, Basel
2021
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.
