Glycine

Glycine

Glycine is the smallest and most abundant amino acid in your body. Your body synthesizes ~3g/day, but collagen turnover alone may demand 10–12g/day (Meléndez-Hevia et al. 2009, computational estimate from a single modelling study — not a directly measured requirement). Modern diets stripped out the main sources — bone broth, skin, cartilage, connective tissue. Classified as conditionally essential: your body makes it, but likely not enough for optimal function.

Key takeaways

• 3g before bed — most-tested sleep protocol; lowers core body temperature via peripheral vasodilation; improves subjective sleep quality and next-day alertness (Bannai et al. 2012)
• 10–15g/day estimated total need — your body makes ~3g/day; the remainder must come from diet or supplementation to cover collagen, glutathione, creatine, and other synthesis demands (single computational estimate — see note above)
• Collagen is ~33% glycine — joints, skin, tendons, gut lining, and bones all depend on glycine as a rate-limiting building block
• GlyNAC (glycine + NAC) — combination corrects age-related glutathione decline by >100% and improves multiple aging hallmarks in RCTs (Sekhar 2023); independently replicated
• Balances high-meat diets — eating lots of muscle meat creates an amino acid imbalance; glycine mimics methionine restriction in animal and mechanistic models, though human longevity evidence is limited
• Known caution — rapidly dividing cancer cells consume glycine as a substrate (Jain et al. 2012, in-vitro); not evidence that dietary glycine causes cancer, but high-dose supplementation warrants caution in individuals with active malignancy

What glycine does

• Collagen synthesis — collagen is ~33% glycine by weight (every third position in the triple helix). Without sufficient glycine, collagen production is rate-limited regardless of vitamin C or proline status. Joints (~67% collagen by dry weight), skin, tendons, ligaments, bones, and gut lining all depend on it. Note: no human clinical trials have tested isolated glycine supplementation for joint outcomes — the collagen evidence primarily uses collagen peptides (15g/day).
• Glutathione production — glycine is one of three amino acids (with cysteine and glutamic acid) required to synthesise glutathione, the body’s primary intracellular antioxidant. In older adults, glycine appears to be the rate-limiting precursor; GlyNAC supplementation corrected glutathione deficiency by 121% at 2 weeks and 164% at 16 weeks in a placebo-controlled RCT (Sekhar 2023).
• Creatine synthesis — your liver uses glycine (along with arginine and methionine) to make creatine. High-meat diets raise creatine demand further. See the creatine module.
• Sleep — 3g glycine before bed reduces core body temperature via peripheral vasodilation (blood flows to hands and feet, cooling the core). Bannai et al. (2012) showed reduced daytime fatigue and improved psychomotor vigilance in sleep-restricted subjects. Evidence is from small trials with subjective endpoints. See the sleep module for full sleep architecture details.
• Methionine balance — muscle meat is high in methionine and low in glycine. Glycine supplementation mimics methionine restriction, activating longevity-related pathways (AMPK, autophagy) in animal models (Zhang et al. 2022). Evidence in humans is limited to observational and mechanistic data. The review by Kumar et al. 2023 supports the mechanism but notes industry affiliation (Tally Health).
• Anti-inflammatory / antioxidant — glycine supplementation reduced oxidative stress markers and improved antioxidant status in human trials (Cruz et al. 2008; Sekhar 2023). These are surrogate endpoints — no hard health outcome data from glycine supplementation alone.
• Neurotransmitter — glycine acts as an inhibitory neurotransmitter in the brainstem and spinal cord. It is also a co-agonist at NMDA glutamate receptors (see cautions below).

GlyNAC — glycine + N-acetylcysteine

GlyNAC combines the two rate-limiting glutathione precursors: glycine (rate-limiting in aging) and NAC (provides cysteine). This combination has shown the most compelling clinical results for glycine-related supplementation:

• Baylor RCT (Sekhar 2023, PMID:35975308): 16-week placebo-controlled trial in 24 older adults. GlyNAC (not placebo) improved glutathione levels, oxidative stress, mitochondrial fatty acid oxidation, insulin resistance, inflammation, endothelial function, gait speed, grip strength, 6-minute walk distance, waist circumference, and systolic blood pressure. NIH-funded.
• USC replication (2025): Independent institution confirmed GlyNAC benefits for glutathione, oxidative stress, and physical function in older adults.
• Typical dose: 100 mg/kg/day each of glycine and NAC (~7g each for a 70kg adult).

Limitations: Small sample sizes (n=24); primary investigator developed the GlyNAC concept; 16-week duration; larger multi-centre trials needed. The combination is promising but not yet supported by the kind of large-scale evidence that would warrant a strong recommendation.

Doses

Timing: 3g before bed for sleep; remaining daily dose can be split across meals or taken with food. Glycine is slightly sweet and dissolves easily in water.

Sources

• Body synthesis — ~3g/day endogenous production (insufficient for estimated needs)
• Bone broth — ~1–2g glycine per cup from cartilage-rich cuts; long simmer (12+ hours) required
• Gelatin / collagen — gelatin is ~27% glycine; among the richest whole-food sources
• Animal and fish skin — skin, cartilage, and connective tissue are high in glycine; muscle meat is the part lowest in glycine
• Glycine powder — pure, dissolves in water or food; one of the cheapest supplements available (~$0.05–0.10/dose)
• Vitamin C is required to hydroxylate proline and incorporate glycine into functional collagen — ensure adequate intake alongside
• Vitamin B6 supports the AGT enzyme that prevents glycine → oxalate conversion — relevant at higher doses
• Check klatiCHECK for klati approved sources

Risks, cautions, and open questions

The post above describes the benefits. This section covers what could go wrong or what remains uncertain.

Cancer metabolism concern

Rapidly proliferating cancer cells consume glycine as a metabolic substrate. Jain et al. (2012, Nature) profiled the NCI-60 cancer cell panel and found glycine consumption correlated with proliferation rate; depriving cancer cells of exogenous glycine selectively impaired rapid division. The serine-glycine-one-carbon (SGOC) metabolic pathway is now a recognised therapeutic target in oncology.

This does NOT mean dietary glycine causes cancer. The in-vitro finding shows that cancer cells already present can use glycine as fuel. There are no human studies linking glycine supplementation to cancer incidence. However, as a precautionary measure: individuals with active malignancy or undergoing cancer treatment should discuss glycine supplementation with their oncologist before taking high doses.

Oxalate and kidney stone risk

Excess glycine can be converted to glyoxalate → oxalate via D-amino acid oxidase. Vitamin B6 (as cofactor for alanine-glyoxalate aminotransferase) redirects glyoxalate back to glycine, reducing oxalate formation. At standard doses (3–10g/day), this is unlikely to be clinically significant for healthy individuals. At higher doses or in individuals with a history of calcium oxalate kidney stones, ensuring adequate B6 status is prudent.

NMDA receptor co-agonism

Glycine is a required co-agonist for NMDA-type glutamate receptors — this is why 30–60g doses have been studied in schizophrenia (to enhance NMDA signalling). At typical supplemental doses (3–10g), the NMDA effect is minimal in healthy adults. However, glycine may interact with clozapine and other antipsychotic medications. Individuals on such medications should consult their prescriber.

GI effects at very high doses

Nausea and dry mouth were the most commonly reported side effects at 30–60g/day in psychiatric trials over 6–28 weeks. At 3–10g/day, GI issues are rare.

Open questions

• The 10–12g/day “requirement” is a computational estimate from one modelling study — no direct metabolic balance study has confirmed this number in humans.
• No human clinical trial has tested glycine alone for joint health outcomes; collagen peptide trials (which contain glycine) show joint benefit, but isolating glycine’s contribution is not yet possible.
• The methionine-restriction longevity benefit is established in animal models but unproven in humans.
• Long-term safety data beyond 28 weeks at any dose are sparse.

Research