Tier 3 — preclinical

Induction of glutathione biosynthesis by glycine-based treatment mitigates atherosclerosis

Rom O, Liu Y, Finney AC, Ghrayeb A, Zhao Y, Shukha Y, Wang L, Rajanayake KK, Das S, Rashdan NA, Weissman N, Delgadillo L, Wen B, Garcia-Barrio MT, Aviram M, Kevil CG, Yurdagul A Jr, Pattillo CB, Zhang J, Sun D, Hayek T, Gottlieb E, Mor I, Chen YE
Redox biology 2022 52:102313

Bibliography

PubMed
PMID 35447412
PubMed Central
PMC9044008
DOI
10.1016/j.redox.2022.102313
Funding
Support included NIH, American Heart Association, Michigan-Israel Partnership and Israel Science Foundation grants.
Competing interests
Several authors filed a relevant tripeptide patent application. Y.E. Chen founded Diapin Therapeutics, which supplied DT-109.

Study snapshot

DesignHuman association/genetic analyses with animal experiments
ModelHuman CAD samples; ApoE-deficient mice; macrophages
SampleHuman CAD samples, atherosclerosis-prone mice and macrophage experiments; n varies by component
InterventionGlycine restriction/supplementation and the tripeptide DT-109
DurationModel-specific intervention periods
EndpointsAtherosclerotic lesions; Glutathione synthesis; Oxidative stress

What the study showed, in plain terms

This translational study supports a link between glycine availability, glutathione and atherosclerosis in experimental models. Some of the strongest intervention findings involved DT-109, a distinct glycine-containing tripeptide.

Key findings

  • Glycine deficiency worsened atherosclerosis in the tested mice.
  • Supplementation and especially DT-109 attenuated selected lesion and oxidative-stress measures.

What this study can and cannot tell us

Human data were associative; there was no human efficacy trial.

DT-109 cannot be treated as ordinary glycine, and later mouse/genetic findings have not uniformly supported causality.

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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