Highlights
- •Genetics has confirmed that hypovitaminosis D is one of the risk factors for MS.
- •A modulation of the global risk for MS may exist from conception to the disease onset.
- •The main mechanism of action of vitamin D in MS appears to be immunomodulatory.
- •Vitamin D could mainly be active in the inflammatory component of MS.
- •Systematic moderate vitamin D supplementation of MS patients is recommended.
Abstract
The most recent findings linking exposure to sun and vitamin D insufficiency to multiple
sclerosis (MS) are reviewed. Due to insufficient sunshine and changing lifestyles,
hypovitaminosis D is widespread in temperate countries. Numerous epidemiological studies
have strongly suggested that sunshine and vitamin D insufficiency contributes to MS
risk in these countries. Moreover, several large genetic studies in MS patients have
recently stated unequivocally that diverse abnormalities involving vitamin D metabolism
are related to the risk of the disease. The important implications of such results
are discussed here. Then, the interactions of hypovitaminosis D with the other genetic
and environmental protective and risk factors, such as the allele HLA DRB1*1501, Epstein-Barr
virus infection, obesity, smoking and sexual hormones, are summarized. Vitamin D insufficiency
and sufficiency could be a risk and a protective factor, respectively, among many
other factors possibly continuously modulating the global MS risk from the mother's
pregnancy to the triggering of MS in adulthood. However, many interactions between
these different factors occur more particularly between conception and the end of
adolescence, which corresponds to the period of maturation of the immune system and
thymus and may be related to the dysimmune nature of the disease. The main mechanisms
of action of vitamin D in MS appear to be immunomodulatory, involving the various
categories of T and B lymphocytes in the general immune system, but neuroprotector
and neurotrophic mechanisms could also be exerted at the central nervous system level.
Furthermore, several controlled immunological studies performed in MS patients have
recently confirmed that vitamin D supplementation has multiple beneficial immunomodulatory
effects. However, there is still an enduring absence of major conclusive randomized
clinical trials testing vitamin D supplementation in MS patients because of the quasi-insurmountable
practical difficulties that exist nowadays in conducting and completing over several
years such studies involving the use of a vitamin. Nevertheless, it should be noted
that similar robust statistical models used in five different association studies
have already predicted a favorable vitamin D effect reducing relapses by 50–70%. If
there is now little doubt that vitamin D exerts a beneficial action on the inflammatory
component of MS, the results are as yet much less clear for the progressive degenerative
component. Lastly, until more information becomes available, vitamin D supplementation
of MS patients, using a moderate physiological dose essentially correcting their vitamin
insufficiency, is recommended.
Abbreviations:
anti-EBNA1 (antibodies against EBV antigen nuclear 1), CIS (clinically isolated syndrome), CNS (central nervous system), CYP27B1 (enzyme 1α-hydroxylase), EAE (experimental autoimmune encephalopathy), EBV (Epstein–Barr virus), HLA (human leukocyte antigen), MS (multiple sclerosis), RCTs (randomized clinical trials), UVB (ultraviolet B rays), VDR (vitamin D receptor), VDRE (vitamin D responsive element), Tregs (T regulator lymphocytes)Key words
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Article info
Publication history
Published online: March 28, 2017
Accepted:
March 27,
2017
Received in revised form:
March 23,
2017
Received:
February 14,
2017
Identification
Copyright
© 2017 Elsevier B.V. All rights reserved.
