INTRODUCTION: Low-to-moderate intensity exercise improves muscle contractile properties and endurance capacity in multiple sclerosis (MS). The impact of high intensity exercise remains unknown. METHODS: Thirty-four MS patients were randomized into a sedentary control group (SED, n = 11) and 2 exercise groups that performed 12 weeks of a high intensity interval (HITR, n = 12) or high intensity continuous cardiovascular training (HCTR, n = 11), both in combination with resistance training. M vastus lateralis fiber cross sectional area (CSA) and proportion, knee-flexor/extensor strength, body composition, maximal endurance capacity and self-reported physical activity levels were assessed before and after 12 weeks. RESULTS: Compared to SED, 12 weeks of high intensity exercise increased mean fiber CSA (HITR +21 +/- 7%, HCTR +23 +/- 5%). Furthermore, fiber type I CSA increased in HCTR (+29 +/- 6%), whereas type II (+23 +/- 7%) and IIa (+23 +/- 6%) CSA increased in HITR. Muscle strength improved in HITR and HCTR (between +13 +/- 7% and +45 +/- 20%) and body fat percentage tended to decrease (HITR -3.9 +/- 2.0% and HCTR -2.5 +/- 1.2%). Furthermore, endurance capacity (Wmax +21 +/- 4%, time to exhaustion +24 +/- 5%, VO2max +17 +/- 5%) and lean tissue mass (+1.4 +/- 0.5%) only increased in HITR. Finally self-reported physical activity levels increased 73 +/- 19% and 86 +/- 27% in HCTR and HITR, respectively. CONCLUSION: High intensity cardiovascular exercise combined with resistance training was safe, well tolerated and improved muscle contractile characteristics and endurance capacity in MS. TRIAL REGISTRATION: ClinicalTrials.gov NCT01845896.

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