Calorie restriction diets and changes in the metabolome in people with multiple sclerosis
ECTRIMS Online Library. Fitzgerald K. 10/27/17; 200899; P1244
Kathryn C. Fitzgerald
Kathryn C. Fitzgerald
Contributions
Abstract

Abstract: P1244

Type: Poster

Abstract Category: Therapy - disease modifying - 32 Others

Background: Intermittent fasting or calorie restriction diets may provide additional anti-inflammatory and neuroprotective advantages beyond the benefits obtained from weight loss alone. In the mouse form of multiple sclerosis (MS), fasting delays the onset of the disease, reduces pro-inflammatory cytokines and promotes oligodendrocyte regeneration. However, data in humans are lacking.
Methods: We conducted a controlled feeding study of different calorie restriction diets in 36 people with MS over 8 weeks. Energy expenditure was determined using indirect calorimetry. Patients were randomized to receive 1 of 3 diets: an intermittent calorie restriction diet (75% reduction in calorie needs 2 days/week; 100% of daily needs 5 days/week), a continuous calorie restriction diet (22% daily reduction in energy needs), and a weight-stable diet (100% of daily calorie needs). Participants provided morning blood samples for metabolomics at baseline and during weeks 4 and 8. To estimate the short term effects of aggressive calorie reduction 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. Those randomized to calorie restriction diets lost an average of 7.3(SD: 4.6)lbs over 8 weeks; changes in weight (P=0.12) 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 derivatives 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. We observed notable changes in lipid metabolites (with relevance to neurologic and immunologic function) occurring over time and following a short-term aggressive reduction in calorie intake. Further studies will integrate changes in the metabolome with changes in the gut microbiota.
Disclosure:
Kathryn Fitzgerald receives postdoctoral fellowship support from the National MS Society and from NARCOMS.
Diane Vizthum: nothing to disclose
Bobbie Henry Barron: nothing to disclose
David Baer: nothing to disclose
Patrick Sullivan: nothing to disclose
Ellen Mowry receives research funding from the National MS Society (RG4407A2, Harry Weaver Award) and Department of Defense. Teva Neuroscience provides free glatiramer acetate for the investigator-initiated vitamin D trial, of which she is the am PI. She is also the PI of investigator-initiated studies funded by Biogen, Sanofi-Genzyme. She is also a site investigator of trials sponsored by Sun Pharma, Biogen and receives royalties from Up to Date.

Abstract: P1244

Type: Poster

Abstract Category: Therapy - disease modifying - 32 Others

Background: Intermittent fasting or calorie restriction diets may provide additional anti-inflammatory and neuroprotective advantages beyond the benefits obtained from weight loss alone. In the mouse form of multiple sclerosis (MS), fasting delays the onset of the disease, reduces pro-inflammatory cytokines and promotes oligodendrocyte regeneration. However, data in humans are lacking.
Methods: We conducted a controlled feeding study of different calorie restriction diets in 36 people with MS over 8 weeks. Energy expenditure was determined using indirect calorimetry. Patients were randomized to receive 1 of 3 diets: an intermittent calorie restriction diet (75% reduction in calorie needs 2 days/week; 100% of daily needs 5 days/week), a continuous calorie restriction diet (22% daily reduction in energy needs), and a weight-stable diet (100% of daily calorie needs). Participants provided morning blood samples for metabolomics at baseline and during weeks 4 and 8. To estimate the short term effects of aggressive calorie reduction 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. Those randomized to calorie restriction diets lost an average of 7.3(SD: 4.6)lbs over 8 weeks; changes in weight (P=0.12) 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 derivatives 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. We observed notable changes in lipid metabolites (with relevance to neurologic and immunologic function) occurring over time and following a short-term aggressive reduction in calorie intake. Further studies will integrate changes in the metabolome with changes in the gut microbiota.
Disclosure:
Kathryn Fitzgerald receives postdoctoral fellowship support from the National MS Society and from NARCOMS.
Diane Vizthum: nothing to disclose
Bobbie Henry Barron: nothing to disclose
David Baer: nothing to disclose
Patrick Sullivan: nothing to disclose
Ellen Mowry receives research funding from the National MS Society (RG4407A2, Harry Weaver Award) and Department of Defense. Teva Neuroscience provides free glatiramer acetate for the investigator-initiated vitamin D trial, of which she is the am PI. She is also the PI of investigator-initiated studies funded by Biogen, Sanofi-Genzyme. She is also a site investigator of trials sponsored by Sun Pharma, Biogen and receives royalties from Up to Date.

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies