Abstract
Background: Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system in young adults that may lead to progressive disability. Since pharmacological treatments may have substantial side effects, there is a need for complementary treatment options such as specific dietary approaches. Ketone bodies that are produced during fasting (FD) and ketogenic diets (KD) are an alternative and presumably more efficient energy source for the brain. Studies on mice with experimental autoimmune encephalomyelitis showed beneficial effects of KD and FD on disease progression, disability, cognition and inflammatory markers. However, clinical evidence on these diets is scarce. In the clinical study protocol presented here, we investigate if a KD and a FD are superior to a standard diet (SD) in terms of therapeutic effects and disease progression. Methods: This study is a single-center, randomized, controlled, parallel-group study. One hundred and eleven patients with relapsing-remitting MS with current disease activity and stable immunomodulatory therapy or no disease-modifying therapy will be randomized to one of three 18-month dietary interventions. The dietary interventions are 1) a KD with a restricted carbohydrate intake of 20-40 g/day, 2) a FD with a 7 day fast every 6 months and 14 hours daily intermittent fasting in between, and 3) a fat-modified SD as recommended by the German Nutrition Society. The primary outcome measure is the number of new T2-weighted MRI lesions after 18 months. Secondary endpoints are safety, changes in relapse rate, disability progression, fatigue, depression, cognition, quality of life, changes of gut microbiome as well as markers of inflammation, oxidative stress and autophagy. Safety and feasibility will also be assessed. Discussion: Preclinical data suggest that KD and FD may modulate immunity, reduce disease severity and promote remyelination in the mouse model of MS. However, clinical evidence is lacking. This study is the first clinical study investigating the effects of a KD and FD on disease progression of MS. Trial Registration: ClinicalTrials.gov; NCT03508414; Registered 25 April 2018, retrospectively registered; https://clinicaltrials.gov/ct2/show/NCT03508414
Dietary interventions for multiple sclerosis-related outcomes
