From Association to Action: Personalizing Lifestyle Interventions in Multiple Sclerosis-A Critical Narrative Review

Lifestyle factors are increasingly incorporated into multiple sclerosis (MS) care, but association, modifiability and therapeutic justification are not equivalent. This critical narrative review examines when a lifestyle exposure should become a clinical target after MS diagnosis. Evidence across physical activity and exercise, smoking, obesity and cardiometabolic health, diet, sleep, psychological stress, vitamin D and sun exposure, cognitive reserve and engagement, and alcohol is interpreted through the sequence modifiable exposure → post-diagnostic prognostic relevance → deliberate intervention → verified target modification (target engagement) → demonstrated clinical benefit, while distinguishing general-health benefit, MS-relevant clinical benefit and evidence for MS disease-course modification. The strength and completeness of this evidence vary substantially across domains. Smoking cessation and physical activity provide particularly strong grounds for clinical action, whereas several other exposures show larger gaps between prognostic association and intervention evidence. Multidomain intervention is not inherently personalized; personalization requires selection and prioritization of targets according to the intended outcome, strength of evidence, individual relevance and feasibility, followed by verification that the target changed and that the expected benefit occurred. Lifestyle intervention should complement, not substitute for, disease-modifying therapy, and no MS-directed intervention may be the appropriate personalized decision when a clinically relevant or sufficiently supported target is absent. The objective is therefore to support proportionate lifestyle decisions in which the intervention, intended outcome and therapeutic claim are matched to the available evidence and the individual clinical context.