Tier 4 — mechanistic

Dietary Choline and Betaine Intake and 2-year Changes in Cognitive Function in Older Adults With Overweight or Obesity and Metabolic Syndrome: A Prospective Cohort Analysis

Héctor Vázquez-Lorente, José María Manzanares-Errazu, Nancy Babio, Miguel Ruiz-Canela, Dolores Corella, Javi Hernando, José Alfredo Martínez, Ángel M Alonso-Gómez, Julia Wärnberg, Jesús Vioque, Dora Romaguera, José López-Miranda, Ramon Estruch, Francisco J Tinahones, Víctor Urbano-Fernández, Lluís Serra-Majem, Naomi Cano-Ibáñez, Josep A Tur, Vicente Martín Sánchez, Xavier Pintó, Miguel Delgado-Rodríguez, Pilar Matía-Martín, Josep Vidal, Clotilde Vázquez, Emili Ros, Fernando Fernández-Aranda, Estefanía Toledo, Liliana Gutiérrez-Carrasquilla, José V Sorlí, María Dolores Zomeño, Antonio Garcia-Rios, Alejandro Oncina-Canovas, Raquel Cueto-Galán, María Angeles Zulet, Lara Prohens, Rosa Casas, María Durán-Luque, Lucas Tojal-Sierra, Víctor Simón-Frapolli, Zenaida Vázquez-Ruiz, Rebeca Fernández-Carrión, Olga Castañer, Aquiles Lozano Rodriguez-Mancheño, Alberto Asencio, Ana García-Arellano, Montse Fitó, Lidia Daimiel, Jordi Salas-Salvadó
The American journal of clinical nutrition 2026 123(5):101265

Bibliography

PubMed
PMID 41825530
PubMed Central
PMC13197923
DOI
10.1016/j.ajcnut.2026.101265
Funding
Reported funding/support: This study was supported by the official Spanish Institutions for Funding Scientific Biomedical Research, CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), and Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigación para la Salud (FIS), which is cofunded by the European Regional Development Fund (6 coordinated FIS projects led by JSS and JV, including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, PI19/01332, PI20/01802, PI20/00138, PI20/01532, PI20/00456, PI20/00339, PI20/00557, PI20/00886, and PI20/01158); the Especial Action Project entitled: Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus grant to JSS; the European Research Council (Advanced Research Grant 2014–2019; agreement #340918) granted to MMG; the Recercaixa (number 2013ACUP00194) grant to JSS; grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016, and PI0137/2018); the PROMETEO/21/2021 and the AICO/2021/347 grants from the Generalitat Valenciana; and the Horizon 2020 PRIME study (Prevention and Remediation of Insulin Multimorbidity in Europe; grant agreement #847879). HVL holds a Sara Borrell (CD25/00181) research contract from Instituto de Salud Carlos III, cofounded by the European Social Fund (ESF). None of the funding sources took part in the design, collection, analysis, interpretation of the data, or writing the report, or in the decision to submit the manuscript for publication. JSS, senior author, gratefully acknowledges the financial support by ICREA under the ICREA Academia program.
Competing interests
Reported disclosure: The authors declare that there are no known financial interests or personal relationships that could have appeared to influence the work reported in this manuscript.

Study snapshot

DesignProspective cohort analysis within PREDIMED-Plus
ModelHuman participants
Sample6610 adults aged 55-75 with metabolic syndrome
InterventionHabitual dietary choline and/or betaine intake; no randomized TMG treatment
Duration2 years
EndpointsCognitive change

What the study showed, in plain terms

Published in 2026, this source examined human observational and biomarker research. Design: Prospective cohort analysis within PREDIMED-Plus. Sample/model: 6610 adults aged 55-75 with metabolic syndrome. The exposure or intervention was Habitual dietary choline and/or betaine intake; no randomized TMG treatment. Follow-up or treatment period: 2 years.

Higher dietary betaine was associated with modest improvements in selected cognitive domains, including language.

Observational exposure analysis: residual confounding and reverse causation remain possible. Associations do not establish that betaine supplementation causes the same outcome.

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Key findings

  • Higher dietary betaine was associated with modest improvements in selected cognitive domains, including language.
  • The recorded outcome domains were Cognitive change.
  • The exposure was observed rather than assigned as an isolated supplement treatment.

What this study can and cannot tell us

  • Observational exposure analysis: residual confounding and reverse causation remain possible. Associations do not establish that betaine supplementation causes the same outcome.
  • Confounding, dietary patterns, illness, medication use and reverse causation can influence an association. Blood or dietary concentrations do not identify the effect of starting a capsule.
  • Source basis: Accessible full-text extract plus indexed bibliographic data. Missing method details, funding information or participant denominators are not inferred.

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Editorial review

Reviewed by the Biohack Blueprint research team

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology