The Molecular Mechanisms of Vitamin A Deficiency in Multiple Sclerosis

Abstract

Vitamin A, considered to be an essential nutrient, has important actions in immunological responses and the central nervous system (CNS). Neuroimmunological functions of vitamin A are mediated through its active metabolite, retinoic acid (RA). In the CNS, RA contributes to regeneration and plasticity, while also playing a key role in enhancing tolerance and reducing inflammatory responses by regulating T cell, B cell and dendritic cell populations. However, evidence has indicated lower plasma levels of vitamin A in patients with multiple sclerosis (MS). Vitamin A deficiency leads to dysregulation of immune tolerance and pathogenic immune cell production in this disease. Vitamin A may ameliorate MS pathogenesis through numerous mechanisms including a reduction in inflammatory processes by re-establishing the balance between pathogenic (Th1, Th17, Th9) and immunoprotective cells (Th2, Tregs), modulating B cell and dendritic cell function as well as increasing tolerance of autoimmunity and regeneration in the CNS. Thus, the results from the current review suggest that vitamin A can be considered as a potential treatment in MS disease management.

Nutrition in Multiple Sclerosis: An integrative review of scientific publications from the last 5 years

“…There was also a predominance of studies (19.0%; n= 12) that assessed the role of antioxidant vitamins (A, C and/or E) in the development and/or evolution of MS [9][10][11][12][13][14][15][16][17][18][19][20] and the influence of some natural bioactive compounds, flavonoids and non-flavonoids with antioxidant and/or anti-inflammatory power (12.7%, n= 8), in the disease development, in particular in demyelination 21 control, and consequently, in the progress of symptoms such as muscular weakness and fatigue 22 .…”

“…There were a total of 101 dietary components/nutritional patterns studied because some studies assessed more than one of these components. 56 ; Jelinek et al 52 ; Koriem 57 ; Malli et al 31 ; Masullo et al 13 ; Peterlik 58 ; Polachini et al 16 ; Romero et al 59 ; Schmitz et al 18 ; Shiri-Shahsavar et al 19 ; Torkildsen et al 20 63 ; Hoare et al 62 ; Mauriz et al 14 ; Nieto et al 15 ; Pantzaris et al 61 ; Rezapour-Firouzi et al 28 ; Rezapour-Firouzi et al 30 ; Schmitz et al 18 ; Shiri-Shahsavar et al 19 ; Timmermans et al 60 ; Weiland et al 43 Antioxidant Vitamins 12 19.0 Dorosty-Motlagh et al 9 ; Geldern; Mowry 10 ; Honarvar et al 11 ; Loken-Amsrud 12 ; Masullo et al 13 ; Mauriz et al 14 ; Nieto et al 15 ; Polachini et al 16 ; Saboor-Yaraghi et al 17 ; Schmitz et al 18 ; Shiri-Shahsavar et al 19 ; Torkildsen et al 20 Bioactive compounds 8 12. Hagan et al 35 ; Jelinek et al 36 ; Oliveira et al 37 ; Wens et al 38 .…”

Elucidating the Molecular Basis of Multiple Sclerosis and Understanding the Disease Pathophysiology

“…They are able to recruit neutrophils into the CNS and induce further inflammatory reactions. Also, both Th17 cells and IL-17 were found to be elevated in several studies in the active form of MS [2,31]. IL-17 functions in induction of pro-inflammatory cytokines and chemokines, enhancing DC maturation and promoting neutrophil functions [57].…”

“…In MS cases, such supplementation leads to decreased myelin oligodendrocytes glycoprotein-reactive cells, reduces IL-17 levels, promotes TGF-β production as well as elevates Foxp3 expression [31].…”

“…More so, IL-17 increases BBB permeability upon binding to IL-17R and promotes further inflammatory cell migration into the CNS. Notably, MS endothelium showed increased levels of IL-17R expression [31].…”