The Impact of Micronutrients and Dietary Supplements on the Immune System in Multiple Sclerosis

Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) that leads to myelin degradation and neuronal damage. MS symptoms detrimentally affect the quality of life and expectancy in MS patients. It affects frequently peoples, aged between 18 and 40 years, with an incidence 2–3 times higher in women. . MS can be arranged conforming to its clinical course in four various types of MS could be distinguished: relapsing remitting MS (RRMS), primary progressive MS (PPMS), secondary progressive MS (SPMS) and progressive-relapsing MS. Experimental animal pattern for the MS disease that commonly used is Experimental autoimmune encephalomyelitis (EAE) .inflammation, demyelination, axonal loss and gliosis in EAE associated with interaction among a variety of immunopathological mechanisms. The results of immunological, histopathological, and genetic studies on MS patients suggest that autoimmunity plays an important role in the pathogenesis of this disease. Th17 cells are thought to play an important role in the onset of the early phase of MS, while Th1 cells are involved in the late stages of CNS inflammation. Decreased number of regulatory T cells as well as dysfunction of these cells have been observed in MS patients. The results of previous studies showed a significant association between dietary supplements and the onset and progression of the MS disease. Researchers in last years, becoming more interest about relationship among the dietary MS and supplementation.  Supplementation with Vitamin D, vitamin A, Curcumin, Omega-3 and omega-6 fatty acids improve the patientchr('39')s physiological symptoms and increase life expectancy and reduce the symptoms of MS. Vitamin D establish an essential fat-soluble vitamin obtained through exposure to sunlight as well as dietary origin such as animal protein, fish liver oil, and fortified dairy and cereal products. The cellular mechanisms of vitamin D are mediated by the Vitamin D receptor (VDR). VDR is one of transcription factor that belong  steroid superfamily of nuclear receptors .heterodimer form of Ligand-bound VDR  and retinoid X receptor (RXR), together becomes translocated to the nucleus where it performs its functions on gene regulation. The vitamin D effects are associated with cell type-specific and depend on VDR/ RXR binding, which is influenced by the cellular chromatin condition and the availability of interacting DNA-binding protein component. VDR/RXR as nuclear receptors associated with a diversity of coactivators and corepressors in cells and resulting in local epigenetic changes that have either permissive or repressive effects on gene expression. DNA methylation, histone modifications and expression of noncoding RNAs (ncRNAs), which is important for cell survival and its physiological function are epigenetic condition comprises highly interconnected mechanisms. Vitamin D has impact on histone modifications and VDR/RXR associations with deacetylases, histone methyl transferases and histone acetyltransferases that its access on DNA methylation is just beginning to emerge. Curcumin (diferuloylmethane) origin turmeric plant Curcuma longa and its derivatives known as curcuminoids have been identified to be effective in experimental studies. In addition, curcumin has been tested as an anti-inflammatory agent for treatment of cancers and other diseases. Curcumin exerts its beneficial effects by anti-oxidative, anti-proliferative and anti-inflammatory properties and is commonly used in traditional medicine to treat inflammation and promote wound healing.  Moreover, curcumin has been gradually used as an auxiliary drug for various diseases, such as cancer, arthritis, and immune diseases. Curcumin exerts its beneficial effects by anti-oxidative, anti-proliferative and anti-inflammatory properties and is commonly used in traditional medicine to treat inflammation and promote wound healing .Curcumin inhibits EAE in association with the inhibition of neural antigen-specific Th1 and Th17 cell differentiation. Curcumin modulates Th1/Th17 responses by acting directly on T cells and indirectly by attenuating IL-12/IL-23 production by antigen presenting cells (APCs) in EAE and can improve the severity of symptoms in the Spinal Cord Injury (SCI) model by modulating the mammalian target of rapamycin (mTOR) Pathway signaling.  Curcumin enhances neurotrophic factors and repair mechanisms in CNS via repair of myelin. The proteins and cells involved in the immune system have specific actions and role. The role of T-helper 17(Th17) cells and T regulatory (Treg) cells in MS pathogenesis, the effect of vitamin A, and of its active metabolite retinoic acid (RA), as well as the management of inflammation, have been well analyzed, mainly in in vitro studies. Also it is known that in MS, the balance between Th17 cells and Treg cells is diminished. Vitamin A may amend MS pathogenesis via several mechanisms. Those mechanisms include the reduction of inflammatory processes by re-balancing pathogenic (Th1, Th17, Th9) and immune-protective (Th2, Treg) cells, modulating the B-cell and dendritic cell functions, as well as increasing autoimmunity and regeneration tolerance in the CNS . The aim of this study was to investigate the importance of micronutrients and dietary supplements on the immune system in MS. Thus, vitamin A could be considered as a potential co-treatment agent in MS disease management. Data of this review study were collected from PubMed, Science Direct, and Google Scholar databases from 2000 to 2019 and keywords like “Multiple Sclerosis, Vitamin D, Calcitriol, Retinoic acid, Vitamin A, Curcumin, Omega 3 and Omega 6 fatty acids” were used in this search.