Fasting, ketogenic and anti-inflammatory diets stabilized active relapsing-remitting multiple sclerosis over 18 months, a randomized, controlled study

Background: Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system in young adulthood leading to disability and early retirement. Ketone-based diets improve the disease course in MS animal models and health outcomes in different pilot studies of neurodegenerative diseases. Methods: We enrolled 105 individuals with relapsing-remitting MS (RRMS) in an 18-month, randomized, controlled study, and randomized them into 1) standard healthy diet (SD) as recommended by the German Nutrition Society, 2) fasting diet (FD) with 7-day fasts every 6 months with intermittent fasting at 6 of 7 days a week or 3) ketogenic diet (KD) with 20-40 g carbohydrates per day. Primary outcome was the number of new MRI lesions after 18 months in the KD and FD compared to SD and compared to baseline. Secondary outcomes included further MRI outcomes, disease biomarkers as well as metabolic, and clinical MS outcomes. Results: Eighty-one participants completed the study. The primary endpoint number of new T2 lesions after 18 months did not change in any of the groups (SD 0 (0-(-1)), FD 0 (2-0), KD 0 (2-0)). Compared to baseline, in the FD group, Neurofilament light chain (NfL) -concentrations were lower at 9 months (-1.94 pg/mL, p = 0.042) and depressive symptoms improved slightly at 18 months (p = 0.079). In the KD group, cognition improved at 18 months (symbol digit modalities test +3.7, p = 0.020). Cardiometabolic risk markers (body mass index, abdominal fat, blood lipids, adipokines, blood pressure) improved in all three groups at 9 months differently and were partially associated with clinical outcomes in the FD and KD group.