Tier 3 — preclinical

Betaine Attenuates Hyperhomocysteinemia-Induced Cognitive Impairment by Suppressing Oxidative Stress and Activating the PI3K/AKT/GSK-3β Pathway

Xiaolong Gu, Yuan Fu, Yongli Zhao, Zhenyi Liu, Yixiao Yang, Qi Xie, Peng Ma, Zhiwei Peng, Zhizhen Liu, Jianting Li, Jun Xie
Antioxidants (Basel, Switzerland) 2026 15(7):807

Bibliography

PubMed
PMID 42510538
PubMed Central
PMC13405995
DOI
10.3390/antiox15070807
Funding
Reported funding/support: National Natural Science Foundation of Chinahttps://ror.org/01h0zpd94 82201841U23A20420Shanxi Basic Research Program202203021212369202403021221156 Science Research Start-up Fund for Doctor of Shanxi Medical Universityhttps://ror.org/0265d1010 XD2114Shanxi Province Higher Education “Billion Project” Science and Technology Guidance ProjectThis study is supported by the National Natural Science Foundation of China (No. 82201841; No. U23A20420), Shanxi Basic Research Program (No. 202203021212369 and 202403021221156) and Science Research Start-up Fund for Doctor of Shanxi Medical University (No. XD2114) and Shanxi Province Higher Education “Billion Project” Science and Technology Guidance Project.
Competing interests
Reported disclosure: The authors declare no conflicts of interest.

Study snapshot

DesignExperimental animal and/or laboratory research
ModelHigh-methionine-fed mice and HT-22 cells
SampleExperiment-specific biological replicates and model groups; see original methods
InterventionExperimental betaine after induced hyperhomocysteinemia
Duration8-week dietary model followed by 14-day supplementation
EndpointsMouse cognition; Tau; Oxidative stress

What the study showed, in plain terms

Published in 2026, this source examined preclinical aging, brain and metabolic mechanisms. Design: Experimental animal and/or laboratory research. Sample/model: Experiment-specific biological replicates and model groups; see original methods. The exposure or intervention was Experimental betaine after induced hyperhomocysteinemia. Follow-up or treatment period: 8-week dietary model followed by 14-day supplementation.

Betaine improved selected cognitive and oxidative-stress measures, with experiments implicating PI3K/AKT/GSK-3beta signaling.

Experimental model evidence. The intervention, concentrations and outcomes do not establish an effective human supplement dose or a clinical treatment benefit.

Continue with TMG Data Center

Continue with TMG, Methylation and MTHFR: Understanding the Evidence

Key findings

  • Betaine improved selected cognitive and oxidative-stress measures, with experiments implicating PI3K/AKT/GSK-3beta signaling.
  • The recorded outcome domains were Mouse cognition; Tau; Oxidative stress.
  • The result applies to the tested exposure: Experimental betaine after induced hyperhomocysteinemia; 8-week dietary model followed by 14-day supplementation.

What this study can and cannot tell us

  • Experimental model evidence. The intervention, concentrations and outcomes do not establish an effective human supplement dose or a clinical treatment benefit.
  • Cell concentrations, species, disease models and experimental routes cannot be converted directly into an effective or safe oral human regimen.
  • Source basis: Accessible full-text extract plus indexed bibliographic data. Missing method details, funding information or participant denominators are not inferred.

Related papers in the corpus

Tier 4
Betaine: A Promising Natural Product for Neurological and Psychiatric Diseases
Ying Zhang et al. · Current neuropharmacology · 2026
Tier 4
Association of trimethylamine oxide and its precursors with cognitive impairment: a systematic review and meta-analysis
Caiyi Long et al. · Frontiers in aging neuroscience · 2024
Tier 2
An open-label, 24-week pilot study of the methyl donor betaine in Alzheimer disease patients
D Knopman et al. · Alzheimer disease and associated disorders · 2001
Tier 4
Global DNA hypomethylation and its correlation to the betaine level in peripheral blood of patients with schizophrenia
Yui Murata et al. · Progress in neuro-psychopharmacology & biological psychiatry · 2020
Tier 3
Systematic profiling reveals betaine as an exercise mimetic for geroprotection
Lingling Geng et al. · Cell · 2025
Tier 4
Betaine and aging: A narrative review of findings, possible mechanisms, research perspectives, and practical recommendations
Emilia Zawieja et al. · Ageing research reviews · 2025

Editorial review

Reviewed by the Biohack Blueprint research team

Last verified

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