Tier 4 — mechanistic

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, Maryse C J Osté, Dennis W Bennett, Elias J Jeyarajah, Irina Shalaurova, Eke G Gruppen, Stanley L Hazen, James D Otvos, Stephan J L Bakker, Robin P F Dullaart, Margery A Connelly
Journal of clinical medicine 2019 8(11):1813

Bibliography

PubMed
PMID 31683780
PubMed Central
PMC6912391
DOI
10.3390/jcm8111813
Funding
Indexed grant support: P01 HL147823 — NHLBI NIH HHS — United States; R01HL103866 — National Institutes of Health (NIH) and Office of Dietary Supplements. The indexed list may not contain the complete funding declaration.
Competing interests
Reported disclosure: E.G., D.W.B., E.J., I.S., J.D.O. and M.A.C. are currently, or were at the time of this study, employees of LabCorp. M.C.J.O., E.G.G., X.S.L., S.J.L.B. and R.P.F.D. have no conflicts of interest to reveal. S.L.H. reports being listed as a co-inventor on pending and issued patents held by the Cleveland Clinic relating to cardiovascular diagnostics and therapeutics, having been paid as a consultant for Proctor & Gamble, and having received research funds from LipoScience, Pfizer, Inc., and Proctor & Gamble.

Study snapshot

DesignProspective cohort with assay validation
ModelHuman participants
Sample4336 PREVEND participants
InterventionMeasured betaine status and related metabolites; no randomized TMG treatment
DurationProspective diabetes follow-up
EndpointsDiabetes incidence; Betaine assay

What the study showed, in plain terms

Published in 2019, this source examined human observational and biomarker research. Design: Prospective cohort with assay validation. Sample/model: 4336 PREVEND participants. The exposure or intervention was Measured betaine status and related metabolites; no randomized TMG treatment. Follow-up or treatment period: Prospective diabetes follow-up.

Higher circulating betaine was associated with lower subsequent type 2 diabetes risk after adjustment.

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 circulating betaine was associated with lower subsequent type 2 diabetes risk after adjustment.
  • The recorded outcome domains were Diabetes incidence; Betaine assay.
  • 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

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