Tier 4 — mechanistic

Betaine and Trimethylamine-N-Oxide as Predictors of Cardiovascular Outcomes Show Different Patterns in Diabetes Mellitus: An Observational Study

Michael Lever, Peter M George, Sandy Slow, David Bellamy, Joanna M Young, Markus Ho, Christopher J McEntyre, Jane L Elmslie, Wendy Atkinson, Sarah L Molyneux, Richard W Troughton, Christopher M Frampton, A Mark Richards, Stephen T Chambers
PloS one 2014 9(12):e114969

Bibliography

PubMed
PMID 25493436
PubMed Central
PMC4262445
DOI
10.1371/journal.pone.0114969
Funding
Reported funding/support: Support from the Heart Foundation of New Zealand (grant 1090) and the Maurice and Phyllis Paykel Trust are acknowledged. The parent CDCS study was funded by the Health Research Council of New Zealand (Programme 02/152). These funding bodies had no role in the conduct of the research or its interpretation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests
Reported disclosure: Competing Interests: The authors have declared that no competing interests exist.

Study snapshot

DesignProspective observational cohort
ModelHuman participants
Sample475 post-coronary-admission patients; 79 with diabetes
InterventionMeasured betaine status and related metabolites; no randomized TMG treatment
DurationMedian follow-up 1804 days
EndpointsCardiovascular events; Diabetes interaction

What the study showed, in plain terms

Published in 2014, this source examined human observational and biomarker research. Design: Prospective observational cohort. Sample/model: 475 post-coronary-admission patients; 79 with diabetes. The exposure or intervention was Measured betaine status and related metabolites; no randomized TMG treatment. Follow-up or treatment period: Median follow-up 1804 days.

Higher betaine predicted more events in patients with diabetes, whereas lower betaine predicted some events in those without diabetes.

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

Continue with TMG Data Center

Continue with TMG for Weight Loss: Body-Fat Findings and Their Limits

Key findings

  • Higher betaine predicted more events in patients with diabetes, whereas lower betaine predicted some events in those without diabetes.
  • The recorded outcome domains were Cardiovascular events; Diabetes interaction.
  • 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.

Related papers in the corpus

Tier 4
Dietary Choline and Betaine Are Not Associated With the Risk of Type 2 Diabetes. A Systematic Review and Meta-Analysis of Observational Studies
Elham Sharifi-Zahabi et al. · Journal of diabetes research · 2026
Tier 2
Metabolic Effects of Betaine: A Randomized Clinical Trial of Betaine Supplementation in Prediabetes
Ana Maria Grizales et al. · The Journal of clinical endocrinology and metabolism · 2018
Tier 4
High Betaine, a Trimethylamine N-Oxide Related Metabolite, Is Prospectively Associated with Low Future Risk of Type 2 Diabetes Mellitus in the PREVEND Study
Erwin Garcia et al. · Journal of clinical medicine · 2019
Tier 4
Associations between Serum Betaine, Methyl-Metabolizing Genetic Polymorphisms and Risk of Incident Type 2 Diabetes: A Prospective Cohort Study in Community-Dwelling Chinese Adults
Xiaoting Lu et al. · Nutrients · 2022
Tier 4
Dietary Choline and Betaine and Risk of CVD: A Systematic Review and Meta-Analysis of Prospective Studies
Katie A Meyer et al. · Nutrients · 2017
Tier 4
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

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