Tier 4 — mechanistic

1H-NMR-based metabolomics identifies disrupted betaine metabolism as distinct serum signature of pre-frailty

Carmen Marino, Alberto Imarisio, Clara Gasparri, Enza Napolitano, Anna Di Maio, Micol Avenali, Gabriele Buongarzone, Caterina Galandra, Marta Picascia, Manuela Grimaldi, Francesco Errico, Mariangela Rondanelli, Anna Maria D'Ursi, Enza Maria Valente, Alessandro Usiello
npj aging 2025 11(1):26

Bibliography

PubMed
PMID 40216769
PubMed Central
PMC11992162
DOI
10.1038/s41514-025-00218-z
Funding
Reported funding/support: http://dx.doi.org/10.13039/501100002803Fondazione Cariplo2017-05752017-0575 http://dx.doi.org/10.13039/501100003196Ministero della SaluteRicerca Corrente 2022-2024 http://dx.doi.org/10.13039/501100021856Ministero dell'Università e della RicercaMNESYS (PE0000006) DN. 1553 11.10.2022PRIN 2022 - COD. 2022XF7YYL_02
Competing interests
Reported disclosure: Competing interests: The authors declare no competing interests.

Study snapshot

DesignCross-sectional metabolomics study
ModelHuman participants
SampleOlder adults across fit, pre-frail and frail groups
InterventionMeasured betaine status and related metabolites; no randomized TMG treatment
DurationSingle serum profiling assessment
EndpointsFrailty biomarkers; Sex differences

What the study showed, in plain terms

Published in 2025, this source examined human observational and biomarker research. Design: Cross-sectional metabolomics study. Sample/model: Older adults across fit, pre-frail and frail groups. The exposure or intervention was Measured betaine status and related metabolites; no randomized TMG treatment. Follow-up or treatment period: Single serum profiling assessment.

Higher serum betaine emerged as a possible pre-frailty signature in women.

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 serum betaine emerged as a possible pre-frailty signature in women.
  • The recorded outcome domains were Frailty biomarkers; Sex differences.
  • 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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Elham Sharifi-Zahabi et al. · Journal of diabetes research · 2026
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Association of choline and betaine with the risk of cardiovascular disease and all-cause mortality: Meta-analysis
Qinglin Yang et al. · European journal of clinical investigation · 2023
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Jiyoung Youn et al. · Clinical nutrition (Edinburgh, Scotland) · 2019

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