Tier 4 — mechanistic

Associations of plasma trimethylamine N-oxide, choline, carnitine, and betaine with inflammatory and cardiometabolic risk biomarkers and the fecal microbiome in the Multiethnic Cohort Adiposity Phenotype Study

Benjamin C Fu, Meredith A J Hullar, Timothy W Randolph, Adrian A Franke, Kristine R Monroe, Iona Cheng, Lynne R Wilkens, John A Shepherd, Margaret M Madeleine, Loïc Le Marchand, Unhee Lim, Johanna W Lampe
The American journal of clinical nutrition 2020 111(6):1226-1234

Bibliography

PubMed
PMID 32055828
PubMed Central
PMC7266689
DOI
10.1093/ajcn/nqaa015
Funding
Reported funding/support: National Institutes of Health10.13039/100000002P01 CA168530P30 CA71789R01 CA204368T32 CA009001T32 CA094880
Competing interests
A competing-interest declaration was not available in the indexed record or accessible disclosure metadata.

Study snapshot

DesignCross-sectional study
ModelHuman participants
Sample1653 older Multiethnic Cohort participants
InterventionMeasured betaine status and related metabolites; no randomized TMG treatment
DurationSingle blood and microbiome assessment
EndpointsInsulin resistance; Metabolites; Microbiome

What the study showed, in plain terms

Published in 2020, this source examined human observational and biomarker research. Design: Cross-sectional study. Sample/model: 1653 older Multiethnic Cohort participants. The exposure or intervention was Measured betaine status and related metabolites; no randomized TMG treatment. Follow-up or treatment period: Single blood and microbiome assessment.

Lower betaine was associated with greater insulin resistance, while other choline-pathway metabolites had different cardiometabolic patterns.

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

  • Lower betaine was associated with greater insulin resistance, while other choline-pathway metabolites had different cardiometabolic patterns.
  • The recorded outcome domains were Insulin resistance; Metabolites; Microbiome.
  • 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: Indexed abstract and 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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Association of choline and betaine levels with cancer incidence and survival: A meta-analysis
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