Evidence map›Paper›PMID 40684250›Full record

Trial reportAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Role of B vitamins in modulating homocysteine and metabolic pathways linked to brain atrophy: Metabolomics insights from the VITACOG trial.

Tereza Kacerova, Abi G Yates, Jiayi Dai, Dawn Shepherd, Elisabete Pires, Sebastian de Jel, Qingxia Gong, Eric Schiffer, Fredrik Jernerén, Thomas Olsen and 6 more

Abstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Trial
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Tereza KacerovaDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, UK.ORCID 0000-0002-9477-0182
Abi G YatesDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, UK.
Jiayi DaiDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, UK.
Dawn ShepherdDepartment of Pharmacology, University of Oxford, Oxford, UK.
Elisabete PiresDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, UK.
Sebastian de Jelnumares AG, Regensburg, Germany.
Qingxia Gongnumares AG, Regensburg, Germany.
Eric Schiffernumares AG, Regensburg, Germany.
Fredrik JernerénDepartment of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
Thomas OlsenDepartment of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
Celeste A De Jager LootsThe Ageing Epidemiology Research Unit, School of Public Health, Imperial College London, Charing Cross Hospital, London, UK.
Helga RefsumDepartment of Pharmacology, University of Oxford, Oxford, UK.
A David SmithDepartment of Pharmacology, University of Oxford, Oxford, UK.
James S O McCullaghDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, UK.
Daniel C AnthonyDepartment of Pharmacology, University of Oxford, Oxford, UK.
Fay ProbertDepartment of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford, UK.

Funding

Alzheimer's Research TrustAqua-Synapse EU framework (European Union's Horizon 2020 Research and Innovation programme under the Marie Sklodowska-Curie Grant Agreement) 101086453Charles Wolfson Charitable TrustDorothy Hodgkin Early Career Fellowship in Chemistry in association with SomervilleEPSRC Doctoral Training Partnership EP/W524311/1Henry Smith CharityJohn Coates Charitable TrustMedical Research CouncilNumares AG (Am Biopark 9, 93053 Regensburg-Graß, Germany)Sidney and Elizabeth Corob Charitable TrustThames Valley Dementias and Neurodegenerative Diseases Research Network of the National Institute for Health Research
6 · The paper itself

Abstract

introductionElevated total homocysteine (tHcy) is a major predictor of brain atrophy, cognitive decline, and Alzheimer's disease (AD) progression. The VITACOG trial, a randomized, placebo-controlled 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.

methodsWe used untargeted, multi-platform metabolomics, with nuclear magnetic resonance and liquid chromatography-mass spectrometry to analyze serum samples from 89 B vitamin-treated and 84 placebo-treated MCI participants over a 2 year follow-up period.

resultsMultivariate modeling distinguished treated from placebo groups with 91.2 ± 1.8% accuracy. B vitamin supplementation induced significant metabolic reprogramming, lowering quinolinic acid, α-ketoglutarate, α-ketobutyrate, glucose, and glutamate. DISCUSSION: These findings reveal that B vitamins influence metabolic pathways beyond tHcy reduction, particularly the tricarboxylic acid cycle and glutamine-glutamate cycling, critical for brain energy homeostasis and neurotransmission. This metabolic signature supports B vitamin supplementation as a strategy for slowing MCI progression. HIGHLIGHTS: Nuclear magnetic resonance and multi-platform liquid chromatography tandem mass spectrometry metabolomics were performed on serum samples from 89 B vitamin-treated and 84 placebo participants in the VITACOG trial. Multi-platform metabolomics revealed B vitamin-driven metabolic reprogramming, achieving 91% classification accuracy. B vitamin supplementation modulates key neuroprotective metabolic pathways. Regulation of energy metabolism and neurotransmission by B vitamins contributes to brain health in elderly individuals. B vitamins demonstrate potential as an adjunct therapy in mild cognitive impairment, potentially mitigating progression to Alzheimer's disease.

Indexed as

BrainCognitive DysfunctionHomocysteineMetabolic Networks and PathwaysVitamin B ComplexAgedAged, 80 and overAtrophyDietary SupplementsDouble-Blind MethodFemaleHumansMagnetic Resonance SpectroscopyMaleMetabolomicsHomocysteineVitamin B ComplexB vitaminscognitive impairmenthomocysteinemass spectrometrynuclear magnetic resonanceuntargeted metabolomics

Identifiers

PMID40684250
PMCPMC12276071

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.