The Hidden Players in Multiple Sclerosis Nutrition: A Narrative Review on the Influence of Vitamins, Polyphenols, Salt, and Essential Metals on Disease and Gut Microbiota.

Multiple sclerosis (MS) is a chronic neuroinflammatory and autoimmune disorder of the central nervous system (CNS) whose cause remains unknown. Disease-modifying therapies (DMTs) are the current standard of care, yet growing evidence highlights the importance of complementary lifestyle-based interventions, including nutrition, in modulating disease activity. Given the influence of diet on immune function, several studies have examined its effects in MS, with particular attention to specific dietary patterns and macronutrients. However, fewer studies have focused on micronutrients, bioactive compounds, and minerals and their influence in MS. In this narrative review, we report the latest evidence on micronutrients such as vitamins and essential metals, along with polyphenols and minerals like salt, in both experimental autoimmune encephalomyelitis (EAE) and MS. We also discuss how these dietary components may influence the gut microbiota, which is considered a contributor to disease onset due to its interaction with the immune system in the gut-brain axis. While findings for vitamins B, C, E, and K remain heterogeneous, vitamins A and D show the most consistent immunological and clinical effects, with immunomodulatory, antioxidative, and neuroprotective effects in both EAE and MS. Polyphenols also display anti-inflammatory and neuroprotective properties in EAE and, to a lesser extent, in clinical studies. Lastly, evidence suggests the importance of balanced salt intake and adequate levels of essential metals, as dysregulation may contribute to comorbidities or enhance inflammatory pathways relevant to MS. Although only a limited number of studies have explored these aspects, the gut microbiota appears to be differentially affected by these dietary factors. Overall, advancing our understanding of how these components interact with immune and microbial pathways may support the development of personalized nutritional strategies to complement current therapies and improve patient outcomes.