Background: Multiple sclerosis (MS) is a progressive, demyelinating condition of the central
nervous system, manifesting in loss or alterations in function of sensory, motor and cognitive function.
Of the various environmental and behavioural risk factors identified as playing a role in MS onset
and progression, perhaps none has been as consistent as vitamin D.
Objective: In this review, we will endeavour to present a general background on the role of vitamin D
in human health and particularly in MS, as well as the substantial epidemiological evidence in support
of vitamin D's role in MS.
Results: Initially identified via the oft-noted latitudinal gradient in MS prevalence and incidence, vitamin
D has since been demonstrated to have a strong and consistent inverse association with MS risk
and clinical course. Cases have much lower levels of the diagnostic metabolite of vitamin D, 25-
hydroxyvitamin D (25(OH)D) compared to healthy controls, while those with more active disease have
lower levels of 25(OH)D than other cases with less active disease. These case-control and crosssectional
study results led the way to cohort studies which indicated significant inverse associations between
serum 25(OH)D and clinical activity in MS. The combined weight of indirect and direct observational
evidence have been the impetus for completed and ongoing randomised trials of vitamin D
supplementation, alone or in addition to standard immunomodulatory medications, as an intervention
in MS onset and clinical course. Moreover, in addition to being a distinct factor in MS aetiology, vitamin
D has been demonstrated to interact with a variety of other risk factors, from genetic predictors
like HLA-DR1 genotype to behavioural factors like smoking.
Conclusion: There is an abundance of epidemiological evidence, both direct and indirect, as well as
significant biological plausibility substantiating a role for vitamin D in the onset & progression of multiple