Associations between lifestyle factors and 2.5-year clinical outcomes differ by time since multiple sclerosis diagnosis

BACKGROUND: Healthy lifestyle factors are associated with better health outcomes in people with multiple sclerosis (pwMS). Whether these associations differ according to time since diagnosis remains unclear. Understanding this may inform optimal timing for lifestyle modification. METHODS: This prospective cohort study included 1,401 pwMS who completed baseline and 2.5-year follow-up surveys from the HOLISM study. Five lifestyle factors were assessed at baseline (high-quality diet, physical activity, smoking status, vitamin D supplementation, meditation). Outcomes included fatigue, depression, and disability. Multivariable log-binomial regression examined associations between individual and multiple lifestyle factors and outcomes stratified by time since diagnosis (≤ 5 vs. > 5 years). RESULTS: Physical activity showed stronger prospective associations with reduced fatigue, depression, and disability among participants within 5 years of diagnosis than among those with longer duration. Non-smoking was associated with lower disability risk within the ≤ 5-year group. In contrast, high-quality diet was associated with lower depression and disability among participants with > 5-year since diagnosis, though non-significant between-group difference. Vitamin D supplementation and meditation were not associated with outcomes. Meeting 4-5 healthy lifestyle criteria was associated with lower depression risk in both duration groups and with lower fatigue and disability risk in the ≤ 5-year group, with a between-group difference for disability. CONCLUSION: Associations between lifestyle factors and MS outcomes may vary across the disease course, suggesting that the duration and timing of lifestyle engagement may influence their potential impact. These findings support further research on stage-specific lifestyle management strategies in MS.