PurposeTo investigate the effects of a multimodal intervention including a modified Paleolithic diet, nutritional supplements, stretching, strengthening exercises with electrical stimulation of trunk and lower limb muscles, meditation and massage on walking performance and balance of subjects with progressive multiple sclerosis (MS).Materials and methodsTwenty subjects with mean (standard deviation) age of 51.7 (6.4) years and Expanded Disability Status Scale score of 6.2 (1) participated in a 12-month study. Assessments were completed at baseline, 3, 6, 9, and 12 months.ResultsThe entire cohort did not show significant changes in any of the assessments over 12 months except higher speed of walking toward the 10 feet mark during timed up and go (TUG) test at 6 months compared with baseline (mean change 7.9 cm/s [95% confidence interval {CI}]: 0.3, 15.2; p=0.041). Sub-group analysis revealed that 50% subjects (n=10) showed decrease in TUG time from baseline to at least 3 of 4 time-points post-intervention and were considered as responders (TUG-Res), the remaining 10 subjects were considered as nonresponders (TUG-NRes). Over 12 months, TUG-Res showed decreased mean TUG time by 31% (95% CI: −52%, −2%), increased median Berg Balance Scale scores (42 to 47), 30% increase in mean timed 25-foot walk speed (>20% considered clinically significant) and increased speed of walk toward 10 feet mark during TUG by 11.6 cm/s (95% CI: −3.0, 25.9) associated with increases in step lengths and decrease in step duration. TUG-NRes showed deterioration in walking ability over 12 months. Comparison of TUG-Res and TUG-NRes showed no significant differences in adherence to intervention but better stride duration and longer step length at baseline for TUG-Res than for TUG-NRes (p<0.05).ConclusionA multimodal lifestyle intervention may improve walking performance and balance in subjects with progressive MS who have mild-to-moderate gait impairment, whereas subjects with severe gait impairments may not respond to this intervention. Future trials should assess effects of this intervention in subjects with MS during early stages of the disease.