Tier 3 — preclinical

Exploring the Role of Glycine Metabolism in Coronary Artery Disease: Insights from Human Genetics and Mouse Models

Biswas S, Hilser JR, Woodward NC, Wang Z, Gukasyan J, Nemet I, Schwartzman WS, Huang P, Han Y, Fouladian Z, Charugundla S, Spencer NJ, Pan C, Tang WHW, Lusis AJ, Hazen SL, Hartiala JA, Allayee H
Nutrients 2025 17(1):198

Bibliography

PubMed
PMID 39796632
PubMed Central
PMC11723402
DOI
10.3390/nu17010198
Funding
NIH support, including the GeneBank research program.
Competing interests
Certain investigators disclosed cardiovascular-diagnostic patents, royalties, consulting and industry research relationships.

Study snapshot

DesignHuman association/genetic analyses with animal experiments
ModelHuman observational/genetic datasets and ApoE-deficient mice
Sample105,718 UK Biobank participants in the clinical association analysis; additional genetic cohorts and mouse experiments
InterventionHuman glycine/CAD analyses and glycine feeding in atherosclerosis-prone ApoE-deficient mice
DurationHuman epidemiology plus controlled mouse feeding
EndpointsCoronary disease associations; Genetic causal inference; Mouse aortic lesions

What the study showed, in plain terms

This 2025 investigation found a favorable clinical association with glycine but did not find supporting causal evidence from its genetic analyses or mouse-feeding experiment. It is a key counterpoint to earlier positive mechanistic studies.

Key findings

  • Higher glycine correlated with lower prevalent coronary-disease risk.
  • The genetic and mouse intervention results did not substantiate a causal antiatherosclerotic effect.

What this study can and cannot tell us

Mixed methods answer different questions and have distinct limitations.

Neither the observational association nor the animal null result alone determines efficacy of human supplementation.

Related papers in the corpus

Tier 4
Plasma Glycine and Risk of Acute Myocardial Infarction in Patients With Suspected Stable Angina Pectoris
Ding Y et al. · Journal of the American Heart Association · 2015
Tier 2
Oral administration of glycine in the prevention of restenosis after coronary angioplasty. A double blind placebo controlled randomized feasibility trial evaluating safety and efficacy of glycine in the prevention of restenosis after angioplasty
Khan M et al. · Acute cardiac care · 2006
Tier 4
Assessing the causal association of glycine with risk of cardio-metabolic diseases
Wittemans LBL et al. · Nature communications · 2019
Tier 4
Genetic Determinants of Circulating Glycine Levels and Risk of Coronary Artery Disease
Jia Q et al. · Journal of the American Heart Association · 2019
Tier 4
The association of genetically determined serum glycine with cardiovascular risk in East Asians
Chang X et al. · Nutrition, metabolism, and cardiovascular diseases : NMCD · 2021
Tier 4
Interplay Between Plasma Glycine and Branched-Chain Amino Acids Contributes to the Development of Hypertension and Coronary Heart Disease
Dziedzic M et al. · Hypertension (Dallas, Tex. : 1979) · 2024

Editorial review

Reviewed by the Biohack Blueprint research team

Last verified

Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction