TY - JOUR
T1 - Metabolic alterations in multiple sclerosis and the impact of vitamin D supplementation
AU - Bhargava, Pavan
AU - Fitzgerald, Kathryn C.
AU - Calabresi, Peter A.
AU - Mowry, Ellen M.
N1 - Funding Information:
Conflict of interest: P.A. Calabresi reports grants from MedImmune, grants from Biogen, grants from Novartis, grants from Teva, personal fees from Biogen, and personal fees from Vertex outside the submitted work. E.M. Mowry reports grants from Biogen, other support from UpToDate, nonfinancial support from Teva, other support from Sun Pharma, other support from Biogen, and grants from Sanofi Genzyme outside the submitted work.
Funding Information:
FUNDING. This study was supported by NIH grant K23 NS067055, grants from the Race to Erase MS, the National Multiple Sclerosis Society, the American Academy of Neurology, and North American Research Committee on Multiple Sclerosis.
Funding Information:
This study was supported by a grant from the Race to Erase MS to EMM and by NIH grant K23 NS067055 to EMM. PB was supported by a Career Transition Award from the National Multiple Sclerosis Society, the John F. Kurtzke clinician scientist development award from the American Academy of Neurology, and a Junior Faculty Award from the Race to Erase MS. KCF was supported by a post-doctoral fellowship from the National Multiple Sclerosis Society and the North American Research Committee on Multiple Sclerosis.
Publisher Copyright:
© 2017 American Society for Clinical Investigation. All rights reserved.
PY - 2017/10/5
Y1 - 2017/10/5
N2 - BACKGROUND. Our goal was to identify changes in the metabolome in multiple sclerosis (MS) and how vitamin D supplementation alters metabolic profiles in MS patients and healthy controls. METHODS. We applied global untargeted metabolomics to plasma from a cross-sectional cohort of age- and sex-matched MS patients and controls and a second longitudinal cohort of MS patients and healthy controls who received 5,000 IU cholecalciferol daily for 90 days. We applied partial least squares discriminant analysis, weighted correlation network analysis (WGCNA), and pathway analysis to the metabolomics data. Generalized estimating equations models were used to assess change in WGCNA-identified module scores or metabolite pathways with vitamin D supplementation. RESULTS. Utilizing multiple analytical techniques, we identified metabolic alterations in oxidative stress (γ-glutamyl amino acid, glutathione) and xenobiotic metabolism (benzoate, caffeine) in MS patients compared with healthy controls in the first cohort. In the vitamin D supplementation cohort, we identified two sets of metabolites altered differentially between MS patients and healthy controls with vitamin D supplementation. The first included markers of oxidative stress and protein oxidation (P = 0.006), while the second contained lysolipids and fatty acids (P = 0.03). CONCLUSIONS. Using metabolomics, we identified alterations in oxidative stress and xenobiotic metabolism in MS patients and subsequently demonstrated a reduction of oxidative stress markers with vitamin D supplementation in healthy controls but not in MS patients. We demonstrate the utility of metabolomics in identifying aberrant metabolic processes and in monitoring the ability of therapeutic interventions to correct these abnormalities.
AB - BACKGROUND. Our goal was to identify changes in the metabolome in multiple sclerosis (MS) and how vitamin D supplementation alters metabolic profiles in MS patients and healthy controls. METHODS. We applied global untargeted metabolomics to plasma from a cross-sectional cohort of age- and sex-matched MS patients and controls and a second longitudinal cohort of MS patients and healthy controls who received 5,000 IU cholecalciferol daily for 90 days. We applied partial least squares discriminant analysis, weighted correlation network analysis (WGCNA), and pathway analysis to the metabolomics data. Generalized estimating equations models were used to assess change in WGCNA-identified module scores or metabolite pathways with vitamin D supplementation. RESULTS. Utilizing multiple analytical techniques, we identified metabolic alterations in oxidative stress (γ-glutamyl amino acid, glutathione) and xenobiotic metabolism (benzoate, caffeine) in MS patients compared with healthy controls in the first cohort. In the vitamin D supplementation cohort, we identified two sets of metabolites altered differentially between MS patients and healthy controls with vitamin D supplementation. The first included markers of oxidative stress and protein oxidation (P = 0.006), while the second contained lysolipids and fatty acids (P = 0.03). CONCLUSIONS. Using metabolomics, we identified alterations in oxidative stress and xenobiotic metabolism in MS patients and subsequently demonstrated a reduction of oxidative stress markers with vitamin D supplementation in healthy controls but not in MS patients. We demonstrate the utility of metabolomics in identifying aberrant metabolic processes and in monitoring the ability of therapeutic interventions to correct these abnormalities.
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U2 - 10.1172/jci.insight.95302
DO - 10.1172/jci.insight.95302
M3 - Article
C2 - 28978801
AN - SCOPUS:85054732521
SN - 2379-3708
VL - 2
JO - JCI Insight
JF - JCI Insight
IS - 19
M1 - e95302
ER -