Vitamin D as a Potential Therapy for Multiple Sclerosis: Where Are We?

Abstract

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system and is caused by an aberrant immune response to myelin sheath. Disease-modifying medications, which mainly aim to suppress such aberrant immune response, have significantly improved MS treatment. However, the disease severity continues to worsen. In contrast, progressively more data suggest that 1,25-dihydroxyvitamin D or 1,25(OH)2D, i.e., the active vitamin D, suppresses the differentiation of potentially pathogenic T cells associated with MS, enhances the differentiation of regulatory T cells that suppress the pathogenic T cells, and promotes remyelination. These novel 1,25(OH)2D functions have encouraged investigators to develop vitamin D as a potential therapy for MS. However, because of the hypercalcemia that is associated with high 1,25(OH)2D concentrations, supplementation of native vitamin D has been a major focus in clinical trials for the treatment of MS, but such trials have produced mixed data. In this article, we will review current progress in the supplementation of different vitamin D forms for the treatment of experimental autoimmune encephalomyelitis (i.e., an MS animal model) as well as MS. Furthermore, we will review alternative strategies that our laboratory and others are pursuing in an attempt to circumvent the hurdles that are hampering the effective use of vitamin D as a potential therapy for MS.

Preclinical Therapy with Vitamin D3 in Experimental Encephalomyelitis: Efficacy and Comparison with Paricalcitol

“…However, nowadays, it is still accepted as necessary, in view of the ethical issues to test new procedures directly in human subjects. Even though most preclinical assays indicated a strong potential of VitD as useful for EAE prevention or therapy, clinical trials with patients revealed mixed data [ 87 ]. Despite the complexity of this subject, we believe that more clinical assays are worthwhile to be conducted and could clarify this controversy.…”

Vitamins D2and D3have overlapping but different effects on human gene expression revealed through analysis of blood transcriptomes in a randomised double-blind placebo-controlled food-fortification trial

“…The immunomodulatory effects of vitamin D on both innate and adaptive immunity are well documented (Liu et al, 2006, Hayes and Nashold, 2018, Teles et al, 2013). Vitamin D supplementation has the potential to ameliorate the symptoms of autoimmune diseases such as multiple sclerosis, as supported by several lines of evidence: the role in promoting differentiation of oligodendrocyte progenitor cells and therefore remyelination of CNS neurons (Gomez-Pinedo et al, 2020); suppression of the differentiation of potentially pathogenic T-cells and enhancement of regulatory T-cell differentiation (Wasnik et al, 2020). However, a recent Cochrane review found little benefit of vitamin D in this context (Jagannath et al, 2018).…”

Vitamins D2 and D3 have overlapping but different effects on human gene expression revealed through analysis of blood transcriptomes in a randomised double-blind placebo-controlled food-fortification trial

“…The immunomodulatory effects of vitamin D on both innate and adaptive immunity are well documented [45][46][47] . Vitamin D supplementation has the potential to ameliorate the symptoms of autoimmune diseases such as multiple sclerosis, as supported by several lines of evidence: the role in promoting differentiation of oligodendrocyte progenitor cells and therefore remyelination of CNS neurons 48 ; suppression of the differentiation of potentially pathogenic T-cells and enhancement of regulatory T-cell differentiation 49 . However, a recent Cochrane review found little benefit of vitamin D in this context 50 .…”