Calorie restriction diets and changes in the metabolome in people with multiple

Background: People with multiple sclerosis (MS) often ask if diet could influence their MS. Intermittent fasting or calorie restriction may provide additional anti‐inflammatory and neuroprotective advantages beyond the positive benefits obtained from weight loss alone. In the mouse forms of MS, fasting delays the onset of the disease, reduces pro‐inflammatory cytokines and promotes oligodendrocyte precursor cell regeneration. However, data in humans are lacking. Methods: We conducted a controlled feeding study of different calorie restriction diets in 36 people with MS for a period of 8 weeks. Energy expenditure was determined using indirect calorimetry, and patients were randomized to receive 1 of 3 diets: a continuous calorie restriction diet (22% daily reduction in energy needs), an intermittent calorie restriction diet (75% reduction in calorie needs 2 days/week; 100% of daily needs 5 days/week), and a weight‐stable diet (100% of daily calorie needs). Participants provided blood samples for metabolomics at baseline and during weeks 4 and 8. To estimate the short term effects of aggressive reduction in calorie intake on the metabolome, all subjects had 2 visits during weeks 4 and 8. Those in the intermittent calorie restriction arm had one of those visits following a 25% intake day. Untargeted metabolomics was performed at each time point (5 total) and identified over 500 metabolites. Results: Of the 36 patients enrolled, 31 (86%) completed the trial. Participants randomized to calorie restriction diets lost an average of 7.3 (SD: 4.6) lbs over 8 weeks; changes in weight (P50.12) did not differ by type of calorie restriction diet. Over time (and associated with weight loss), we observed increases in acyl‐carnitine metabolites (involved in fatty acid metabolism), sphingolipids (fatty acid deriva‐tives largely in cell membranes of brain/nervous tissue) and decreases in plasmalogens and phosphatidyl choline metabolites (both involved in glycerolipid metabolism). Interestingly, similar changes in these metabolites were also observed in the short‐term after aggressive calorie reduction (e.g. between a 25% vs. 100% calorie day). CoNCLusions: In people with MS, calorie restriction diets were associated with weight loss and with significant changes to the circulating metabolome. In particular, we observed notable changes in lipid metabolites (with relevance to neuro‐logic and immunologic function) occurring over time as well as following a short‐term aggressive reduction in calorie intake. Subsequent studies will integrate changes in the metabolome with changes in changes in the gut microbiota.