Background: The multiple sclerosis (MS) community is highly interested in diet as a potential protective factor against disability, but empirical evidence remains limited. Objective: Evaluate associations between patient-reported Mediterranean diet alignment and objective disability in a real-world MS cohort. Methods: Data were analyzed from persons with MS, aged 18–65, who completed the Mediterranean Diet Adherence Screener (MEDAS), MS Functional Composite (MSFC; primary disability metric), and patient-reported outcomes (PROs; disability, gait disturbance, fatigue, anxiety, and depression) as part of our Comprehensive Annual Assessment Program. Multiple regression predicted MSFC (and PROs) with MEDAS after adjusting for demographic (age, sex, race, ethnicity, and socioeconomic status) and health-related (body mass index (BMI), exercise, sleep disturbance, hypertension, diabetes, hyperlipidemia, and smoking) covariates. Results: Higher MEDAS independently predicted better outcomes across MSFC ( z-score, B = 0.10 (95% confidence interval (CI): 0.06, 0.13), β = 0.18, p < 0.001), MSFC components, and PROs in 563 consecutive patients. Each MEDAS point was associated with 15.0% lower risk for MSFC impairment (⩽ 5th percentile on ⩾ 2 tasks; odds ratio (OR) = 0.850; 95% CI: 0.779, 0.928). Higher MEDAS attenuated effects of progressive disease and longer disease duration on disability. Conclusion: With robust control for potential confounds, higher Mediterranean diet alignment predicted lower objective and patient-reported disability. Findings lay the necessary groundwork for longitudinal and interventional studies to guide clinical recommendations in MS.
