{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T09:29:01Z","timestamp":1791538141682,"version":"4.3.4"},"reference-count":44,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T00:00:00Z","timestamp":1777161600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000090","name":"Congressionally Directed Medical Research Programs","doi-asserted-by":"publisher","award":["W81XWH-18-1-0341"],"award-info":[{"award-number":["W81XWH-18-1-0341"]}],"id":[{"id":"10.13039\/100000090","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["CO 2129\/1-1"],"award-info":[{"award-number":["CO 2129\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mult Scler"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Metabolic dysregulations have been reported in multiple sclerosis (MS), but it is unclear whether metabolic profiles at disease onset predict long-term outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>We evaluated whether baseline metabolic profiles at MS onset could predict disease activity\/progression over 5\u2009years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>This prospective study included 468 patients enrolled in the BENEFIT trial at first clinical episode who completed 5\u2009years of follow-up. Untargeted metabolomic profiling of 545 metabolites was performed at baseline using liquid chromatography\u2013mass spectrometry. Associations with clinical and radiological outcomes were assessed using regression models, and machine learning was applied to identify metabolic signatures of worse outcomes. Models were adjusted for demographic, clinical, and lifestyle covariates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Distinct metabolomic signatures were associated with worse 5-year outcomes, including relapses, lesion volume, brain atrophy, and disability (Expanded Disability Status Scale (EDSS), multiple sclerosis functional composite (MSFC)). These signatures modestly improved outcome prediction beyond established predictors, with the largest gain for brain volume loss (area under the curve (AUC)\u2009=\u20090.68\u20130.86). Pathway analysis showed enrichment of nicotinate\/nicotinamide, histidine, and arginine metabolism across several outcomes, with unsaturated fatty acid biosynthesis specifically with relapses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Metabolic profiles in early MS modestly improve the prediction of 5-year outcomes beyond clinical factors. Consistent enrichment across some pathways suggests potential biological relevance, warranting further investigation of individual metabolites.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13524585261435409","type":"journal-article","created":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T17:11:00Z","timestamp":1777223460000},"page":"696-710","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Serum metabolic profile at clinical onset as predictor of multiple sclerosis activity and progression after 5\u2009years"],"prefix":"10.1177","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0441-6268","authenticated-orcid":false,"given":"Xiaojing","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kjetil","family":"Bjornevik","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clary B","family":"Clish","sequence":"additional","affiliation":[{"name":"Metabolomics Platform, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Edan","sequence":"additional","affiliation":[{"name":"CHU H\u00f4pital Pontchaillou, Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S","family":"Freedman","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Ottawa and Ottawa Hospital Research Institute, Ottawa, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Peter","family":"Hartung","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty, Heinrich-Heine Universit\u00e4t, D\u00fcsseldorf, Germany; Brain and Mind Center, Medical Faculty, The University of Sydney, Sydney NSW, Australia; Brain and Mind Centre, The University of Sydney, Sydney NSW, Australia; Department of Neurology, Palacky University Olomouc, Olomouc, Czechia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Montalb\u00e1n","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center of Catalonia (Cemcat), Vall d\u2019Hebron University Hospital, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupert","family":"Sandbrink","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty, Heinrich-Heine Universit\u00e4t, D\u00fcsseldorf, Germany; Sandbrink Drug Development Consulting &amp; Clinical Services (SDDCCS), Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6963-8892","authenticated-orcid":false,"given":"Jens","family":"Kuhle","sequence":"additional","affiliation":[{"name":"Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Departments of Head, Spine and Neuromedicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3543-3706","authenticated-orcid":false,"given":"Frederik","family":"Barkhof","sequence":"additional","affiliation":[{"name":"Department of Radiology &amp; Nuclear Medicine, Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands; Queen Square Institute of Neurology and Centre for Medical Image Computing, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva-Maria","family":"Wicklein","sequence":"additional","affiliation":[{"name":"Bayer AG, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4175-5509","authenticated-orcid":false,"given":"Ludwig","family":"Kappos","sequence":"additional","affiliation":[{"name":"Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Departments of Head, Spine and Neuromedicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Ascherio","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Harvard T.H. 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