Glycine (longevity / metabolic)

What this is

NIA Interventions Testing Program (Miller 2019, Aging Cell) — 8% glycine diet extended median lifespan ~4-6% in both sexes across 3 independent sites with reduced pulmonary adenocarcinoma mortality. Soultoukis 2023 (PMID 37004845) reviews glycine's role mimicking methionine restriction via GNMT-mediated SAM consumption; methionine restriction itself robustly extends lifespan across species. Razak 2023 PRISMA systematic review (GeroScience) covered 11 physiological systems in humans; cardiovascular and nervous-system signals were strongest. 2025 Singapore RCT (Cossiga et al, Scientific Reports, n=19 severe obesity, 100 mg/kg × 2 weeks) — no weight change but significant reductions in plasma triglycerides and aminotransferases plus improved glutamate-serine-glycine MASLD index, supporting glycine as a MASLD-adjacent intervention; larger trial NCT07285135 ongoing. Hannan 2024 Nutrients update review (PMID 39453231) covers exercise/recovery applications. Background: typical Western diet supplies ~3-5 g glycine vs. ~10-15 g daily metabolic demand for collagen turnover and one-carbon flux — chronic shortfall worsens with age. Distinct from Sleep entry (3 g pre-bed) and GlyNAC (paired with NAC for glutathione).

Mechanism

Conditionally essential amino acid; ~33% of collagen by residues; substrate for glutathione/creatine/heme/purines/bile salts; key acceptor for GNMT (glycine N-methyltransferase) which consumes excess SAM (S-adenosylmethionine) — acts as a methionine restriction mimetic; lowered SAM/mTOR signaling permits autophagy; plasma glycine declines with age and is reduced in obesity/MASLD

Dose & route

10-15 g/day in divided doses (covers age-related collagen-turnover shortfall); 100 mg/kg/day in MASLD/obesity trials

Citations

• https://onlinelibrary.wiley.com/doi/10.1111/acel.12953
• https://pubmed.ncbi.nlm.nih.gov/37004845/
• https://link.springer.com/article/10.1007/s11357-023-00970-8
• https://www.nature.com/articles/s41598-025-20511-x
• https://pubmed.ncbi.nlm.nih.gov/39453231/
• https://clinicaltrials.gov/study/NCT07285135

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