Abstract
This narrative review explores the impact of diet and physical exercise both as a risk factor of central nervous system inflammatory diseases, but more importantly as potential adjunctive disease modifiers in Multiple Sclerosis (MS), Neuromyelitis Optica Spectrum Disorders (NMOSD), and Myelin Oligodendrocyte Glycoprotein (MOG) antibody-associated disease (MOGAD). The majority of evidence relies on MS preclinical and clinical studies, but preclinical studies also support the benefit of lifestyle intervention in NMOSD and MOGAD. In MS, adherence to healthy diets (particularly Mediterranean and MIND diets) could lead to a milder disease course with reduced relapse rates, while structured exercise from early disease stages promotes neuroprotection by upregulating neurotrophic factors and preserving brain volume, possibly impacting disease progression. The ketogenic diet and intermittent caloric restriction also showed promising results. Physical activity, including both aerobic training and resistance training, emerges as a potential disease-modifying strategy by promoting neuroprotection, reducing inflammation, and supporting functional and cognitive outcomes, particularly when implemented early in the disease course. A synergistic approach alongside disease-modifying treatments (DMTs) would further positively modulate core pathological processes. Evidence for NMOSD and MOGAD warrants further investigation. We highlight that integrating personalized lifestyle strategies would be beneficial from the early stages. However, future large-scale, standardized trials are required to fully confirm the neuroprotective potential of diet and exercise across the entire spectrum of CNS disorders.