Linking Nutrients to Multiple Sclerosis Pathogenesis: Biological Evidence and Clinical Implications

Multiple Sclerosis (MS) is an autoimmune and neurodegenerative disorder of the central nervous system (CNS), characterized by demyelination, neuronal loss and physical disability. To date, the exact causes of MS remain unknown. Lifestyle factors, in particular diet, have received growing attention due to their impact on human health, their role in modulating disease pathogenesis, and their influence on gut microbiota composition and activity. As a result, numerous studies have been conducted to examine how specific nutrients, and thereby distinct dietary patterns, may affect the onset and progression of MS. In this narrative review, we aim to explore the most recent and updated evidence concerning the role of fatty acids, carbohydrates, proteins and fibers macronutrients in MS development and progression by evaluating the most relevant literature findings from preclinical models, and clinical trials on people with MS. Dietary macronutrients influence MS pathology through immune and gut-brain axis modulation. Diets rich in saturated fats and refined carbohydrates exacerbate neuroinflammation, promote Th1/Th17 polarization, and worsen disease severity. Conversely, monounsaturated and omega-3 polyunsaturated fatty acids, dietary fibers, and adequate tryptophan metabolism exert anti-inflammatory effects, enhance regulatory T cell (Treg) activity, and improve clinical outcomes. Fiber-derived short-chain fatty acids (SCFAs) and omega-3 metabolites also support gut barrier integrity and suppress astrocyte activation. Evidence on dairy, meat and gluten remains inconclusive, though certain milk proteins and certain components of red/processed meat and of wheat may promote inflammation. Overall, anti-inflammatory and fiber-rich diets, such as those emphasizing unsaturated fats and low sugar intake, appear to confer protective effects in MS. The clarification of the role of dietary components in relation to the disease could help to guide patients toward a healthy and balanced diet, with positive effects on their overall health.