{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:12:20Z","timestamp":1790140340133,"version":"4.0.1"},"reference-count":74,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,19]],"date-time":"2025-07-19T00:00:00Z","timestamp":1752883200000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000852","name":"Henry Smith Charity","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000852","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's & Dementia"],"published-print":{"date-parts":[[2025,7]]},"abstract":"Abstract<\/jats:title>\n \n INTRODUCTION<\/jats:title>\n Elevated total homocysteine (tHcy) is a major predictor of brain atrophy, cognitive decline, and Alzheimer's disease (AD) progression. The VITACOG trial, a randomized, placebo\u2010controlled study in mild cognitive impairment (MCI), previously showed that B vitamin supplementation lowered tHcy, slowing brain atrophy and cognitive decline; however, the underlying mechanisms remained unclear.<\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n We used untargeted, multi\u2010platform metabolomics, with nuclear magnetic resonance and liquid chromatography\u2010mass spectrometry to analyze serum samples from 89 B vitamin\u2013treated and 84 placebo\u2010treated MCI participants over a 2 year follow\u2010up period.<\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n Multivariate modeling distinguished treated from placebo groups with 91.2\u00a0\u00b1\u00a01.8% accuracy. B vitamin supplementation induced significant metabolic reprogramming, lowering quinolinic acid, \u03b1\u2010ketoglutarate, \u03b1\u2010ketobutyrate, glucose, and glutamate.<\/jats:p>\n <\/jats:sec>\n \n DISCUSSION<\/jats:title>\n These findings reveal that B vitamins influence metabolic pathways beyond tHcy reduction, particularly the tricarboxylic acid cycle and glutamine\u2013glutamate cycling, critical for brain energy homeostasis and neurotransmission. This metabolic signature supports B vitamin supplementation as a strategy for slowing MCI progression.<\/jats:p>\n <\/jats:sec>\n \n Highlights<\/jats:title>\n \n \n \n Nuclear magnetic resonance and multi\u2010platform liquid chromatography tandem mass spectrometry metabolomics were performed on serum samples from 89 B vitamin\u2013treated and 84 placebo participants in the VITACOG trial.<\/jats:p>\n <\/jats:list-item>\n \n Multi\u2010platform metabolomics revealed B vitamin\u2013driven metabolic reprogramming, achieving 91% classification accuracy.<\/jats:p>\n <\/jats:list-item>\n \n B vitamin supplementation modulates key neuroprotective metabolic pathways.<\/jats:p>\n <\/jats:list-item>\n \n Regulation of energy metabolism and neurotransmission by B vitamins contributes to brain health in elderly individuals.<\/jats:p>\n <\/jats:list-item>\n \n B vitamins demonstrate potential as an adjunct therapy in mild cognitive impairment, potentially mitigating progression to Alzheimer's disease.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/alz.70521","type":"journal-article","created":{"date-parts":[[2025,7,20]],"date-time":"2025-07-20T03:24:56Z","timestamp":1752981896000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Role of B vitamins in modulating homocysteine and metabolic pathways linked to brain atrophy: Metabolomics insights from the VITACOG trial"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9477-0182","authenticated-orcid":false,"given":"Tereza","family":"Kacerova","sequence":"first","affiliation":[{"name":"Department of Chemistry Chemistry Research Laboratory University of Oxford Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abi G.","family":"Yates","sequence":"additional","affiliation":[{"name":"Department of Chemistry Chemistry Research Laboratory University of Oxford Oxford UK"},{"name":"Department of Pharmacology University of Oxford Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Chemistry Chemistry Research Laboratory University of Oxford Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn","family":"Shepherd","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Oxford Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabete","family":"Pires","sequence":"additional","affiliation":[{"name":"Department of Chemistry Chemistry Research Laboratory University of Oxford Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"de Jel","sequence":"additional","affiliation":[{"name":"numares AG Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingxia","family":"Gong","sequence":"additional","affiliation":[{"name":"numares AG Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Schiffer","sequence":"additional","affiliation":[{"name":"numares AG Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrik","family":"Jerner\u00e9n","sequence":"additional","affiliation":[{"name":"Department of\u00a0Pharmaceutical Biosciences Uppsala University Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Olsen","sequence":"additional","affiliation":[{"name":"Department of Nutrition Institute of Basic Medical Sciences Faculty of Medicine, University of Oslo Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celeste A.","family":"De Jager Loots","sequence":"additional","affiliation":[{"name":"The Ageing Epidemiology Research Unit School of Public Health Imperial College London Charing Cross Hospital London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helga","family":"Refsum","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Oxford Oxford UK"},{"name":"Department of Nutrition Institute of Basic Medical Sciences Faculty of Medicine, University of Oslo Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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