# Glycine Supplementation (3g) - Clinical Longevity Review & Consensus Audit > **Consensus Verdict**: Glycine is a foundational longevity amino acid that acts as an obligate NMDA co-agonist in the suprachiasmatic nucleus to induce peripheral vasodilation and core body cooling, while serving as the indispensable rate-limiting substrate for glutathione synthesis (GlyNAC) and collagen structural repair. ## 1. Executive Summary & Scores - **Longevity Evidence Score**: **91/100** - **Evidence Quality Tier**: **silver** - **Human Clinical Evidence Strength**: 93/100 - **Primary Longevity Classification**: supplements - **Safety Margin Score**: 97/100 (Higher is safer) - **Time Burden**: ~1 minutes/day - **Estimated Monthly Cost**: inexpensive - **Adherence Friction**: 1/10 (Lower is easier to sustain) --- ## 2. Biological Mechanisms of Action Human clinical trials (Yamadera et al. 2007, Bannai et al. 2012) prove shortened sleep latency and deepened slow-wave sleep; landmark Stanford study (Kawai et al. 2015) identified SCN thermoregulatory mechanism; Baylor human RCTs prove GlyNAC reverses hallmark aging. --- ## 3. Canonical Longevity Vector Impacts (The 8 Longevity Pillars) - **Heart Health & Endothelial Function**: **58/100** [Rank #101 of 133 in Heart] - Effect: Moderate (Supports nitric oxide synthesis, reduces arterial stiffness, and lowers blood pressure) - Mechanism: Serves as an essential precursor for vascular elastin and glutathione, improving endothelial nitric oxide release and arterial elasticity. - **Brain Longevity & Neuroprotection**: **76/100** [Rank #49 of 141 in Brain] - Effect: Strong (-28% Slow-Wave Sleep Latency, SCN NMDA Co-Agonist, Distal Vasomotor Cooling) - Mechanism: Acts as an obligate co-agonist at NMDA receptors in the suprachiasmatic nucleus (SCN) to trigger peripheral vasodilation and core temperature drop, and exerts inhibitory neurotransmission via brainstem glycine receptors. - **Metabolic Flexibility & Glycemic Control**: **54/100** [Rank #94 of 129 in Metabolic] - Effect: Moderate (Improves insulin sensitivity, stimulates GLP-1 secretion, and mitigates postprandial glucose spikes) - Mechanism: Stimulates intestinal L-cell secretion of glucagon-like peptide-1 (GLP-1) and enhances insulin-mediated cellular glucose uptake. - **Cancer Defense & DNA Repair**: **30/100** [Rank #75 of 120 in Cancer Defense] - Effect: Mild (Antioxidant cellular defense via glutathione replenishment) - Mechanism: Substrate for glutathione synthesis, neutralizing reactive oxygen species that cause somatic DNA mutations. - **Endocrine & Anabolic Balance**: **32/100** [Rank #59 of 120 in Endocrine] - Effect: Mild (Amino acid substrate for steroidogenic hormone and collagen synthesis) - Mechanism: Supports testicular connective tissue structural integrity and systemic anabolic amino acid availability. - **Chronic Inflammation Reduction**: **65/100** [Rank #93 of 126 in Inflammation] - Effect: Moderate-Strong (Substrate for glutathione synthesis alongside cysteine, suppressing systemic ROS) - Mechanism: Inhibits inflammatory macrophage cytokine production and serves as the rate-limiting backbone for intracellular glutathione. - **Bone Density & Connective Matrix**: **68/100** [Rank #56 of 142 in Bone Matrix] - Effect: Moderate-Strong (Comprises 33% of amino acid residues in triple-helical type I/III collagen) - Mechanism: Every third amino acid residue in triple-helical collagen is glycine; mandatory rate-limiting substrate for bone collagen lattice and cartilage repair. - **Cellular Longevity & Autophagy**: **85/100** [Rank #43 of 131 in Cellular] - Effect: Strong (Essential rate-limiting substrate for glutathione replenishment, reversing mitochondrial oxidative decay) - Mechanism: Direct precursor alongside cysteine for de novo glutathione biosynthesis (GlyNAC), reversing age-related mitochondrial dysfunction and genomic oxidative damage. --- ## 4. Practical Protocol & Administration Guidelines - **Standard Clinical Dosage**: Refer to individualized clinical assessment - **Recommended Timing**: Consistent daily schedule - **Administration Type**: Behavioral / Compound - **Recommended Biomarkers to Monitor**: sleep_quality, sleep_latency, soreness, waking_restedness, bone_density, heart_health --- ## 5. Safety, Contraindications & Drug Interactions - **Contraindications**: Anuria / end-stage renal disease without specialist nephrology oversight - **Safety Profile**: High Margin - Mild osmotic softening of stool if taken in single boluses exceeding 15 grams; Transient nausea if taken on an entirely empty stomach without fluid --- ## 6. Peer-Reviewed Human Clinical Trials & Key PMIDs 1. **Dietary glycine supplementation protects against muscle wasting and enhances tendon collagen synthesis** [PMID: 24615238] - Link: https://pubmed.ncbi.nlm.nih.gov/24615238/ 2. **The Sleep-Promoting Action of Glycine is Mediated by Peripheral Cutaneous Vasodilation** [PMID: 25533534] - Link: https://pubmed.ncbi.nlm.nih.gov/25533534/ 3. **The sleep-promoting and hypothermic effects of glycine are mediated by NMDA receptors in the suprachiasmatic nucleus** [PMID: 17456740] - Link: https://pubmed.ncbi.nlm.nih.gov/17456740/ 4. **Subjective effects of glycine on sleep quality in healthy volunteers with unsatisfactory sleep** [PMID: 17610547] - Link: https://pubmed.ncbi.nlm.nih.gov/17610547/ 5. **Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes** [PMID: 22529837] - Link: https://pubmed.ncbi.nlm.nih.gov/22529837/ 6. **Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency and Aging Hallmarks** [PMID: 35999978] - Link: https://pubmed.ncbi.nlm.nih.gov/35999978/ --- ## 7. Canonical Citation & Web Verification - **Official Web Review**: [Glycine Supplementation (3g) on LongevityReviews](https://longevityreviews.org/modalities/glycine) - **Last Evidence Calibration**: 2026-09-09 - **Review Policy**: 0% sponsored placements, independent peer-reviewed consensus.