Evidence map›Paper›PMID 40107652›Full record

Trial reportMetabolism: clinical and experimental2025

A multi-metabolite signature robustly predicts long-term mortality in the PREDIMED trial and several US cohorts.

Gonzalo Fernández-Duval, Cristina Razquin, Fenglei Wang, Huan Yun, Jie Hu, Marta Guasch-Ferré, Kathryn Rexrode, Raji Balasubramanian, Jesús García-Gavilán, Miguel Ruiz-Canela and 18 more

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

Trial report in Metabolism: clinical and experimental, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Dogs and humans share biomarkers of mortality.The journals of gerontology. Series A, Biological sciences and medical sciences · 2026
    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

28 authors.

Gonzalo Fernández-DuvalDepartment of Preventive Medicine and Public Health, Navarra Health Research Institute (IdiSNA), University of Navarra, Pamplona, Spain; Institute of Data Science and Artificial Intelligence (DATAI), University of Navarra, Pamplona, Spain. Electronic address: ghfernandezd@unav.es.
Cristina RazquinDepartment of Preventive Medicine and Public Health, Navarra Health Research Institute (IdiSNA), University of Navarra, Pamplona, Spain; Consorcio CIBER, Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
Fenglei WangDepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Huan YunDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Jie HuDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Marta Guasch-FerréDepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Public Health, Section of Epidemiology, University of Copenhagen, Copenhagen, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Kathryn RexrodeDivision of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Division of Women's Health, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Raji BalasubramanianDivision of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Division of Women's Health, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Jesús García-GavilánConsorcio CIBER, Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Unitat de Nutrició Humana, Reus, Spain; Institut d'Investigació Sanitària Pere Virgili (IISPV), Reus, Spain.
Miguel Ruiz-CanelaDepartment of Preventive Medicine and Public Health, Navarra Health Research Institute (IdiSNA), University of Navarra, Pamplona, Spain; Consorcio CIBER, Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
Clary B ClishMetabolomics Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Dolores CorellaConsorcio CIBER, Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Department of Preventive Medicine and Public Health, University of Valencia, Valencia, Spain.
Enrique Gómez-GraciaDepartment of Preventive Medicine, University of Malaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain.
Miquel FiolConsorcio CIBER, Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Platform for Clinical Trials, Instituto de Investigación Sanitaria Illes Balears (IdISBa), Hospital Universitario Son Espases, Palma de Mallorca, Spain.
Ramón EstruchConsorcio CIBER, Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain.
José LapetraConsorcio CIBER, Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Department of Family Medicine, Research Unity, Distrito Sanitario Atención Primaria Sevilla, Sevilla, Spain.
Montse FitóConsorcio CIBER, Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Hospital del Mar Research Institute, Barcelona, Spain.
Luis Serra-MajemConsorcio CIBER, Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Nutrition Research Group, Research Institute of Biomedical and Health Sciences (IUIBS), University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain.
Emilio RosConsorcio CIBER, Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain.
Liming LiangDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Courtney DennisMetabolomics Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Eva M AsensioConsorcio CIBER, Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Department of Preventive Medicine and Public Health, University of Valencia, Valencia, Spain.
Olga CastañerConsorcio CIBER, Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Hospital del Mar Research Institute, Barcelona, Spain.
Francisco J PlanesInstitute of Data Science and Artificial Intelligence (DATAI), University of Navarra, Pamplona, Spain; Tecnun School of Engineering, University of Navarra, San Sebastián, Spain; Biomedical Engineering Center, University of Navarra, Pamplona, Spain.
Jordi Salas-SalvadóConsorcio CIBER, Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Unitat de Nutrició Humana, Reus, Spain; Institut d'Investigació Sanitària Pere Virgili (IISPV), Reus, Spain.
Frank B HuDepartment 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; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Estefanía ToledoDepartment of Preventive Medicine and Public Health, Navarra Health Research Institute (IdiSNA), University of Navarra, Pamplona, Spain; Consorcio CIBER, Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
Miguel A Martínez-GonzálezDepartment of Preventive Medicine and Public Health, Navarra Health Research Institute (IdiSNA), University of Navarra, Pamplona, Spain; Consorcio CIBER, Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Funding

STATISTICAL INNOVATIONS IN RISK MODELINGP01CA087969 · BRIGHAM AND WOMEN'S HOSPITAL · 2000 to 2005
$22.5M
Risk Factors for Breast Cancer in Younger NursesR01CA050385 · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · 1989 to 2005
$10.4M
THE PURPOSE OF THIS MODIFICATION IS TO DE-OBLIGATE NHLBI FUNDING FROM THE WOMEN'S HEALTH INITIATIVE (WHI) - CLINICAL COORDINATING CENTER (CCC).75N92021D00001 · FRED HUTCHINSON CANCER CENTER · 2025 to 2025
$9.3M
BIOCHEMICAL MARKERS IN THE NURSES'HEALTH STUDY COHORTR01CA049449 · BRIGHAM AND WOMEN'S HOSPITAL · 1989 to 2005
$7.7M
Life Course Cancer Epidemiology Cohort in WomenU01CA176726 · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · 2025 to 2025
$6.4M
ROLE OF DIETARY CONSTITUENTS ON GENE EXPRESSION IN INTESTINAL EPITHELIUMP30DK040561 · MASSACHUSETTS GENERAL HOSPITAL · 1994 to 2025
$6.0M
SIGNAL TRANSDUCTION IN HUMAN ABDOMINAL AND GLUTEOFEMORAL ADIPOCYTESP30DK046200 · TUFTS MEDICAL CENTER · 1992 to 2005
$5.3M
RISK FACTORS FOR CVD IN WOMENR01HL034594 · TULANE UNIVERSITY OF LOUISIANA · 1985 to 2025
$3.5M
Premenopausal Hormone Levels and Risk of Breast CancerR01CA067262 · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · 2002 to 2005
$2.7M
Integrating lifecourse approaches, biologic and digital phenotypes in support of heart and lung disease epidemiologic researchU01HL145386 · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · 2025 to 2025
$2.5M
DIETARY ETIOLOGIES OF HEART DISEASE AND CANCERR01HL035464 · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · 1986 to 2005
$2.2M
Hormone, cytokine, and genetic risks for RA in womenR01AR049880 · BRIGHAM AND WOMEN'S HOSPITAL · 2003 to 2005
$1.5M
NCI NIH HHS P01 CA087969NCI NIH HHS R01 CA049449NCI NIH HHS R01 CA050385NCI NIH HHS R01 CA067262NCI NIH HHS U01 CA167552NCI NIH HHS U01 CA176726NCI NIH HHS UM1 CA186107NHLBI NIH HHS 75N92021D00001NHLBI NIH HHS 75N92021D00002NHLBI NIH HHS R01 HL034594NHLBI NIH HHS R01 HL035464NHLBI NIH HHS R01 HL060712NHLBI NIH HHS R01 HL088521NHLBI NIH HHS R01 HL118264NHLBI NIH HHS U01 HL145386NIAMS NIH HHS R01 AR049880NIDDK NIH HHS P30 DK040561NIDDK NIH HHS P30 DK046200NIDDK NIH HHS R01 DK112940NIDDK NIH HHS R01 DK119268NIDDK NIH HHS R01 DK120870NIDDK NIH HHS R01 DK127601WHI NIH HHS 75N92021D00003WHI NIH HHS 75N92021D00004WHI NIH HHS 75N92021D00005
6 · The paper itself

Abstract

Metabolome-based biomarkers contribute to identify mechanisms of disease and to a better understanding of overall mortality. In a long-term follow-up subsample (n = 1878) of the PREDIMED trial, among 337 candidate baseline plasma metabolites repeatedly assessed at baseline and after 1 year, 38 plasma metabolites were identified as predictors of all-cause mortality. Gamma-amino-butyric acid (GABA), homoarginine, serine, creatine, 1-methylnicotinamide and a set of sphingomyelins, plasmalogens, phosphatidylethanolamines and cholesterol esters were inversely associated with all-cause mortality, whereas plasma dimethylguanidino valeric acid (DMGV), choline, short and long-chain acylcarnitines, 4-acetamidobutanoate, pseudouridine, 7-methylguanine, N6-acetyllysine, phenylacetylglutamine and creatinine were associated with higher mortality. The multi-metabolite signature created as a linear combination of these selected metabolites, also showed a strong association with all-cause mortality using plasma samples collected at 1-year follow-up in PREDIMED. This association was subsequently confirmed in 4 independent American cohorts, validating the signature as a consistent predictor of all-cause mortality across diverse populations.

Indexed as

MetabolomeMortalityAgedAged, 80 and overBiomarkersCohort StudiesFemaleFollow-Up StudiesHumansMaleMiddle AgedUnited StatesBiomarkersAll-cause mortalityBiomarkersMetabolomicMetabolomic signaturePlasma metabolites

Identifiers

PMID40107652
PMCPMC12245597

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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 Socratic graph.