Tier 4 — mechanistic

Plasma homocysteine, dietary B vitamins, betaine, and choline and risk of peripheral artery disease

Monica L Bertoia, Jennifer K Pai, John P Cooke, Michel M Joosten, Murray A Mittleman, Eric B Rimm, Kenneth J Mukamal
Atherosclerosis 2014 235(1):94-101

Bibliography

PubMed
PMID 24819748
PubMed Central
PMC4102310
DOI
10.1016/j.atherosclerosis.2014.04.010
Funding
Indexed grant support: R01 HL091874 — NHLBI NIH HHS — United States; P01 CA087969 — NCI NIH HHS — United States; R01 CA49449 — NCI NIH HHS — United States; UM1 CA167552 — NCI NIH HHS — United States; R01 HL035464 — NHLBI NIH HHS — United States; R01 CA049449 — NCI NIH HHS — United States; P01 CA87969 — NCI NIH HHS — United States; R01 HL034594 — NHLBI NIH HHS — United States. The indexed list may not contain the complete funding declaration.
Competing interests
A competing-interest declaration was not available in the indexed record or accessible disclosure metadata.

Study snapshot

DesignProspective cohorts and nested case-control analyses
ModelHuman participants
Sample72348 women and 44504 men; 790 peripheral-artery cases in dietary analyses
InterventionHabitual dietary choline and/or betaine intake; no randomized TMG treatment
DurationUp to about two decades of follow-up
EndpointsPeripheral-artery disease

What the study showed, in plain terms

Published in 2014, this source examined human observational and biomarker research. Design: Prospective cohorts and nested case-control analyses. Sample/model: 72348 women and 44504 men; 790 peripheral-artery cases in dietary analyses. The exposure or intervention was Habitual dietary choline and/or betaine intake; no randomized TMG treatment. Follow-up or treatment period: Up to about two decades of follow-up.

Dietary betaine and choline were not consistently associated with peripheral-artery disease, unlike some sex-specific homocysteine and folate findings.

Observational exposure analysis: residual confounding and reverse causation remain possible. Associations do not establish that betaine supplementation causes the same outcome. Diet recall, case selection or illness-related metabolite changes may introduce bias.

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Key findings

  • Dietary betaine and choline were not consistently associated with peripheral-artery disease, unlike some sex-specific homocysteine and folate findings.
  • The recorded outcome domains were Peripheral-artery disease.
  • 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. Diet recall, case selection or illness-related metabolite changes may introduce bias.
  • 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

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Dietary Choline and Betaine and Risk of CVD: A Systematic Review and Meta-Analysis of Prospective Studies
Katie A Meyer et al. · Nutrients · 2017
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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