Immunoregulatory effects and therapeutic potential of vitamin D in multiple sclerosis

Abstract

Initially recognised as an important factor for bone health, vitamin D is now known to have a range of effects on the immune system. Vitamin D deficiency is associated with an increased risk of multiple sclerosis (MS), a chronic immune-mediated demyelinating disease of the CNS. In this review, we explore the links between vitamin D deficiency, MS risk, and disease activity. We also discuss the known immune effects of vitamin D supplementation and the relevance of these observations to the immunopathology of MS. Finally, we review the existing evidence for vitamin D supplementation as an MS therapy, highlighting several recent clinical studies and trials.

Keywords: cholecalciferol; genetic; immune; multiple sclerosis; supplementation; therapeutic; transcriptome; treatment; vitamin D.

FIGURE 1

Structural formulae of vitamin D₂ (ergocalciferol) (a) and vitamin D₃ (cholecalciferol) (b), respectively (Wishart et al., 2018)

FIGURE 2

Metabolism and mechanism of action of vitamin D. Vitamin D is either synthesised in the skin during UVB exposure or obtained through intake from supplementation or dietary sources. Vitamin D is then metabolised first to 25(OH)D by the liver and then to 1,25(OH)₂D, which is its active form, by the kidney. The kidney can also metabolise 1,25(OH)₂D to the inactive calcitroic acid by the action of CYP24A1. Many target cells have the metabolic enzymes required to convert vitamin D to its active form. In the target cell, 1,25(OH)₂D binds to vitamin D receptor (VDR) and retinoid X receptor (RXR). This complex then binds to the genome at vitamin D response elements to modulate gene expression