Randomized Clinical Trial of Intermittent Calorie Restriction in People with Multiple Sclerosis: Effects on Immunometabolic and Cognitive Measures

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Abstract BACKGROUND Intermittent calorie restriction (iCR) reduces inflammation in preclinical models and in people with Multiple Sclerosis (pwMS). Mechanisms could be related to changes in levels of adipose tissue-derived adipokines with reduced systemic inflammation and gut microbiota composition. AIMS Evaluate the effects of iCR on adipokines levels, metabolic and immune/inflammatory biomarkers compared to a control unrestricted diet (Ctr) in pwMS. METHODS PwMS (relapsing Remitting MS) were randomly assigned to the iCR or Ctr groups for 12 weeks. Blood was collected at baseline, 6 and 12 weeks. Leptin and adiponectin levels, peripheral blood metabolic and immunologic profiling, anthropometric and total body fat measures, and clinical and cognitive measures were evaluated. Differences between iCR and Ctr were examined using a linear, repeated measures mixed model and adjusted for baseline levels, age, sex and DMTs. RESULTS 42 pwMS were randomized (iCR=22 and Ctr=20). 34 pwMS completed the study (iCR=17 and Ctr=17). PwMS on iCR showed a significant reduction of anthropometric (weight and BMI) and body adiposity measures (waist circumference and fat mass) over the 12 weeks. Leptin levels decreased and were significantly lower in the iCR group at 6 weeks and approaching significance at 12 weeks. Adiponectin increased from baseline in the iCR group at 6 and 12 weeks. The iCR group showed a significant decrease in Th1 cells and an increase in CD45RO+ regulatory T cells after 6 weeks. Cognitive testing using symbol digit modality test showed significantly greater improvement in the iCR group versus Ctr at 12 weeks. CONCLUSIONS Short term iCR is safe and feasible in pwMS, and it can ameliorate metabolic, immunologic, and cognitive profiles. National Multiple Sclerosis Society # RG-1607-25158

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