Roberta Lanzillo, M Clerico, S. Stranges
Multiple sclerosis (MS) is a chronic, immune-mediated neurological disorder characterized by inflammation, demyelination, and progressive neurodegeneration. While genetic susceptibility contributes to disease risk, a growing body of evidence highlights the crucial role of modifiable lifestyle factors in influencing MS onset, disease activity, progression, and overall quality of life. In this narrative review, we explored the relevant literature from commonly used datasets (PubMed, Scopus, Google Scholar), using search terms such as "Lifestyle and Multiple Sclerosis", "Diet and Multiple Sclerosis", "Sleep and Multiple Sclerosis", "Alcohol consumption and Multiple Sclerosis", and "Physical Activity and Multiple Sclerosis". Obesity, particularly during adolescence, has emerged as a significant risk factor for MS, acting through immunometabolic mechanisms such as chronic low-grade inflammation, insulin resistance, and dysregulated adipokine signaling. Sleep disturbances are increasingly recognized as contributors to neuroinflammation and cognitive dysfunction, potentially mediated by impaired glymphatic clearance. Smoking is consistently associated with accelerated disability progression, while alcohol consumption shows dose-dependent effects, with excessive intake negatively impacting sleep and glymphatic function. Overall, lifestyle factors converge on shared biological pathways involving immune regulation, metabolic health, vascular integrity, and glymphatic function. Integrating evidence-based lifestyle counseling with disease-modifying therapies may represent a complementary strategy to optimize long-term outcomes in people with MS, while highlighting key areas for future translational and clinical research.