The Role of Vitamin D in Neuroprotection in Multiple Sclerosis: An Update

Abstract

Multiple sclerosis (MS) is a complex neurological condition that involves both inflammatory demyelinating and neurodegenerative components. MS research and treatments have traditionally focused on immunomodulation, with less investigation of neuroprotection, and this holds true for the role of vitamin D in MS. Researchers have already established that vitamin D plays an anti-inflammatory role in modulating the immune system in MS. More recently, researchers have begun investigating the potential neuroprotective role of vitamin D in MS. The active form of vitamin D, 1,25(OH)2D3, has a range of neuroprotective properties, which may be important in remyelination and/or the prevention of demyelination. The most notable finding relevant to MS is that 1,25(OH)2D3 promotes stem cell proliferation and drives the differentiation of neural stem cells into oligodendrocytes, which carry out remyelination. In addition, 1,25(OH)2D3 counteracts neurodegeneration and oxidative stress by suppressing the activation of reactive astrocytes and M1 microglia. 1,25(OH)2D3 also promotes the expression of various neuroprotective factors, including neurotrophins and antioxidant enzymes. 1,25(OH)2D3 decreases blood–brain barrier permeability, reducing leukocyte recruitment into the central nervous system. These neuroprotective effects, stimulated by 1,25(OH)2D3, all enhance neuronal survival. This review summarizes and connects the current evidence supporting the vitamin D-mediated mechanisms of action for neuroprotection in MS.

Adherence to Mediterranean Diet Is Associated with Multiple Sclerosis Severity

“…The MedDiet is primarily a plant-based dietary pattern characterized by abundance in fruit and vegetables, which are naturally rich in antioxidants, such as vitamins and (poly)phenols. Certain vitamins, including vitamin D, vitamin E, and vitamin C have been shown in experimental models to promote neural stem cell proliferation and differentiation into oligodendrocytes, which carry out remyelination [ 45 ], decrease tau-protein hyperphosphorylation and increase superoxide dismutase and brain-derived neurotrophic factor levels [ 46 ], and more broadly to potentially prevent inflammation and subsequent oxidative damage [ 47 ]. Other non-nutrient compounds, such as (poly)phenols, have been demonstrated to exert neuroprotection through directly counteracting impaired neurogenesis, mitochondrial dysfunction, microglia activation and neuroinflammation (those compounds passing through the blood-brain barrier) [ 48 ] or modulating the gut microbiota toward an anti-inflammatory profile and immunomodulatory activity ultimately resulting, among others, in neuroprotective effects [ 49 ].…”

Risk Factors for Cognitive Impairment in Multiple Sclerosis Patients

“…Regulation of Ca 2+ intake in neurons Astrocyte activation, Oligodendrocyte maturation [51][52][53][54][55]…”

“…Lastly, there is considerable interest in the role of micronutrients in MS, particularly vitamin D. Low serum vitamin D levels were considered for a long time a significant risk factor for the onset and progression of MS [51]; however, only recently was vitamin D deficiency associated with impaired cognition in MS patients [52,53]. Among the most affected cognitive domains, low vitamin D was demonstrated to be a marker of poor information processing speed [54].…”

Multiple sclerosis with comorbidity depression and its association with vitamin D deficiency in a narrative review of the current literature

“…The observed association of s25(OH)D deficiency and increased proinflammatory cytokines as well as increased CRP makes correcting the calcidiol levels by VitD supplementation in order to curb chronic inflammation a logic consequence [179].…”