Glycine
Glycine is a conditionally essential amino acid that restores age-related glutathione deficiency. The GlyNAC protocol (100 mg/kg/day glycine + N-acetylcysteine) raised intracellular GSH by 225% and grip strength 13% in older adults over 16 weeks (Kumar 2021, J Gerontol).
Glycine scored 7.7 / 10 (💪 Strong recommend) on the BioHarmony scale as a Substance → Vitamin / Mineral / Nutrient.
What It Is
Type: Conditionally-essential amino acid (proteinogenic).
Glycine is the simplest amino acid (H2N-CH2-COOH) and a conditionally essential nutrient. Endogenous synthesis from serine via SHMT2 caps around 3 g/day, while daily functional demand for collagen turnover, glutathione regeneration, creatine synthesis, bile acid conjugation, and heme production runs closer to 15 g/day. The deficit widens with age: red blood cell glycine concentrations in healthy elderly run roughly 55% below young controls (218 vs 487 μmol/L, Sekhar 2011), mapping onto the glutathione depletion, mitochondrial dysfunction, and sarcopenia signature of aging.
Three mechanisms carry the biology.
Inhibitory neurotransmission and thermoregulation. Glycine binds strychnine-sensitive glycine-receptor chloride channels in brainstem and spinal cord, and acts as an obligatory co-agonist at the NMDA receptor GluN1 site. Kawai 2015 (Neuropsychopharmacology) dissected the sleep mechanism in rats: 2 g/kg oral glycine increased cutaneous blood flow by 11.3%, dropped core temperature, and accelerated NREM onset. Strychnine did not block the effect (ruling out spinal glycine receptors), but the NMDA antagonists AP5 and CGP78608 abolished it entirely. Lesioning the suprachiasmatic nucleus also abolished it. The active pathway is NMDA co-agonism in the SCN, triggering peripheral vasodilation and the thermoregulatory drop that precedes sleep onset.
Glutathione substrate. GSH is a tripeptide of glutamate, cysteine, and glycine. Cysteine is typically rate-limiting in the young, but glycine becomes co-limiting in aging. The GlyNAC work from Sekhar's group shows that restoring both substrates lifts GSH back toward young-adult levels.
Collagen architecture. Glycine occupies every third residue in the Gly-X-Y repeat of collagen (33% by count), making it structurally non-negotiable for connective tissue synthesis. Hydroxyproline and proline occupy the X and Y positions, but the geometry of the triple helix requires glycine at every third position.
Glycine is also a partial agonist at GABA-A receptors and a substrate for creatine synthesis via GAMT.
Terminology
- GSH: Glutathione, the master intracellular antioxidant. A tripeptide of glutamate, cysteine, and glycine.
- GlyNAC: A combined supplementation protocol of glycine plus N-acetylcysteine, typically dosed at 100 mg/kg/day of each, studied by Sekhar's group at Baylor.
- SHMT2: Serine hydroxymethyltransferase 2, the mitochondrial enzyme that converts serine into glycine; caps endogenous glycine synthesis around 3 g/day.
- NMDA receptor: N-methyl-D-aspartate glutamate receptor. Glycine acts as an obligatory co-agonist at the GluN1 subunit site, required alongside glutamate for receptor activation.
- GlyR: Glycine receptor, a strychnine-sensitive inhibitory chloride channel concentrated in brainstem and spinal cord.
- SCN: Suprachiasmatic nucleus, the hypothalamic master circadian pacemaker that drives peripheral vasodilation and the thermoregulatory drop preceding sleep onset.
- SWS: Slow-wave sleep, deep NREM stages 3-4 where memory consolidation and glymphatic clearance peak.
- PSG: Polysomnography, the gold-standard overnight sleep study measuring EEG, EMG, EOG, respiration, and pulse oximetry.
- IL-6: Interleukin-6, a pro-inflammatory cytokine that rises with age and oxidative stress; central marker in inflammaging.
- SMD: Standardized mean difference, a meta-analytic effect size expressed in standard deviations. |SMD| above 0.8 is large, 0.5 to 0.8 moderate, 0.2 to 0.5 small.
- DSHEA: Dietary Supplement Health and Education Act of 1994, the US law that classifies supplements separately from drugs and food additives.
- GRAS: Generally Recognized As Safe, an FDA designation for food additives deemed safe by qualified experts under intended-use conditions.
Dosing & Protocols
Dosing information is summarized from published research and community reports. This is not a prescribing guide. Consult a healthcare provider before starting any protocol.
View 1 route and 5 protocols
Routes & Forms
| Route | Form | Clinical Range | Community Range |
|---|---|---|---|
| 3 g (sleep) - 0.8 g/kg (schizophrenia adjunct) | 3-15 g/day, split or pre-bed |
Protocols
Sleep onset/quality Clinical
- Dose
- 3 g oral
- Frequency
- 30-60 min pre-bed
- Duration
- indefinite
5-7 nights to evaluate. Escalate to 5 g for non-responders.
GlyNAC longevity stack Clinical
- Dose
- 100 mg/kg/day glycine + 100 mg/kg/day NAC, split
- Frequency
- with meals
- Duration
- 16-24+ weeks
Single research group (Sekhar/Baylor). 7 g + 7 g for a 70 kg adult.
Collagen co-dose Mechanistic
- Dose
- 5-15 g oral
- Frequency
- with or separate from collagen peptides
- Duration
- indefinite
Corrects the amino acid imbalance when dosing collagen peptides alone.
Insulin sensitivity Mixed
- Dose
- 5 g oral
- Frequency
- pre-meal
- Duration
- 8-12 weeks
Díaz-Flores 2013: oxidative stress reduction at 5 g/day × 3 months in metabolic syndrome.
Schizophrenia adjunct (non-clozapine only) Clinical
- Dose
- 0.4-0.8 g/kg/day oral
- Frequency
- split, with antipsychotic
- Duration
- 8+ weeks
Tsai 2006 meta, SMD −1.12 on negative symptoms. Contraindicated with clozapine.
How this score is calculated →
Upside (2.43 / 5.00)
| Dimension | Weight | Score | Visual | Weighted |
|---|---|---|---|---|
| Efficacy | 25% | 3.0 | 0.750 | |
| Breadth of Benefits | 15% | 4.2 | 0.630 | |
| Evidence Quality | 25% | 3.5 | 0.875 | |
| Speed of Onset | 10% | 4.0 | 0.400 | |
| Durability | 10% | 2.0 | 0.200 | |
| Bioindividuality Upside | 15% | 3.8 | 0.570 | |
| Total | 3.425 |
Upside Rationale
Efficacy (3.0/5.0). Single-endpoint effect sizes are modest but replicable across domains. Bannai 2012 (J Pharmacol Sci, n=10 sleep-restricted males) showed 3 g glycine shortened latency to slow-wave sleep by 5-6 minutes on PSG and improved next-day cognition. Yamadera 2007 (n=19) showed subjective sleep quality improvement on the St. Mary's Hospital Sleep Questionnaire. The GlyNAC signal is dramatically larger: Kumar 2021 (J Gerontol, n=24 older adults, 16 weeks) reported intracellular GSH +225%, IL-6 −78%, grip strength +13%, and insulin sensitivity restoration. Attribution to glycine alone vs NAC alone remains uncertain, which caps the Efficacy score below the GlyNAC numbers would suggest in isolation.
Breadth of Benefits (4.2/5.0). Few interventions touch this many domains with a coherent mechanism: sleep, glutathione and oxidative stress, connective tissue and collagen, insulin sensitivity, mood (inhibitory and NMDA modulation), bile acid conjugation, heme synthesis, creatine substrate, and schizophrenia adjunct. The breadth is a structural property of glycine's position in core metabolism, not marketing.
Evidence Quality (3.5/5.0). Mechanistic biochemistry is Nobel-grade. Sleep RCTs are small (n=10-19), mostly Ajinomoto-funded, and rated serious-to-critical risk of bias in the 2024 GeroScience systematic review. GlyNAC studies originate from one group (Sekhar at Baylor) and await independent replication. Tsai 2006 schizophrenia meta (29 RCTs, n=1,253, SMD −1.12 for negative symptoms with non-clozapine antipsychotics) is the most robust clinical meta available. Per v0.5 evidence-integrity rules, industry-funding concentration earns a −0.5 penalty (not −1.0) because there is no burial signal or failed replication, just methodological thinness.
Speed of Onset (4.0/5.0). Sleep effect is measurable night one for responders. Kawai 2015's thermoregulatory vasodilation signature is acute, single-dose. GlyNAC endpoints (GSH, IL-6, grip strength) require 16-24 weeks before clinical signals stabilize.
Durability (2.0/5.0). No tolerance or adaptation is documented, but effects do not persist after cessation. Stop glycine, lose the sleep lift within days. GlyNAC longevity benefits washed out by 3 months post-discontinuation in Kumar 2021 follow-up. Glycine is a consumable, not a permanent upgrade. This is the lowest-scoring dimension.
Bioindividuality Upside (3.8/5.0). The aged, the sarcopenic, vegans and vegetarians (minimal collagen intake), and those on high-methionine diets (which drain glycine via methylation) have the largest headroom. Elderly respond strongest (55% lower baseline RBC glycine). Non-responders for sleep tend to be those whose primary bottleneck is cortisol dysregulation rather than thermoregulatory drive.
Downside (0.18 / 5.00)
| Dimension | Weight | Score | Visual | Weighted |
|---|---|---|---|---|
| Safety Risk | 30% | 1.2 | 0.360 | |
| Side Effect Profile | 15% | 1.3 | 0.195 | |
| Financial Cost | 5% | 1.2 | 0.060 | |
| Time/Effort Burden | 5% | 1.3 | 0.065 | |
| Opportunity Cost | 5% | 1.1 | 0.055 | |
| Dependency / Withdrawal | 15% | 1.0 | 0.150 | |
| Reversibility | 25% | 1.0 | 0.250 | |
| Total | 1.135 | |||
| Harm subtotal × 1.4 | 1.337 | |||
| Opportunity subtotal × 1.0 | 0.180 | |||
| Combined downside | 1.517 | |||
| Baseline offset (constant) | −1.340 | |||
| Effective downside penalty | 0.177 |
Downside Rationale
Safety Risk (1.2/5.0). Glycine is among the safest ingestible compounds studied, with no intrinsic catastrophic adverse event documented across decades of human use (Razak 2017, Oxid Med Cell Longev). Endogenous synthesis already produces ~3 g/day via SHMT2 and typical dietary intake adds 2-5 g/day, so multi-gram supplementation operates inside the body's normal flux range. Regulatory status is unrestricted under DSHEA, and pharma-grade material is widely available. The 2019 FDA action that circulates on forums rescinded a specific direct-food-additive GRAS notification but had no effect on supplement sales. The one mechanistically plausible catastrophic vector is primary hyperoxaluria (glycine routes through glyoxylate to oxalate via glycolate oxidase, and in hyperoxaluria the B6-dependent AGT detox shunt is broken) but this is a rare inborn error, clinically irrelevant in healthy users with adequate B6 status. No FAERS adverse-event cluster, no class-action signal, no intrinsic-organ-toxicity signal in the published or adversarial literature. The v0.5 catastrophic floor is not triggered, so Safety sits near the minimum.
Side Effect Profile (1.3/5.0). The dominant side effect is transient GI discomfort (loose stools, mild nausea) at single oral boluses above ~9 g, which resolves when the dose is split across meals (Razak 2017). Approximately 30% of supplement users report unusually vivid or cinematic dreams, which anecdotally tracks with the GlyR and NMDA co-agonism signature and is experienced as a feature by some and a side effect by others; no pathological sleep architecture disruption has been documented on PSG at therapeutic doses. Occasional mild morning grogginess appears at doses above 5 g pre-bed, particularly in first-week users, and resolves within a few nights or by stepping down to 3 g. Notably absent: no rebound insomnia on cessation, no dependency-type withdrawal, no tolerance. The GlyNAC protocol's split-dosing schedule adds minor compliance friction but no new side-effect category.
Financial Cost (1.2/5.0). Bulk pharma-grade glycine powder from a tested source runs $20-30 per kilogram, which works out to ~333 servings of 3 g or roughly $0.06-0.09 per sleep dose. The GlyNAC protocol at 7 g glycine + 7 g NAC daily costs under $10 per month at bulk pricing. Scored at the accessible bulk-powder channel per v0.5 cost rules rather than branded capsule retail, which can run 10-20× higher. Capsules are economically irrational for a cheap, soluble, mildly-sweet powder; the powder form is both cheaper and more dose-flexible.
Time/Effort Burden (1.3/5.0). A sleep dose is a 15-second operation: one scoop into water or tea, drink, done. Glycine dissolves instantly (unlike magnesium or creatine), tastes mildly sweet, and does not need to be taken with food. The GlyNAC protocol adds mild compliance friction (split dosing across 2-3 meals for 16+ weeks), but total daily effort remains under 2 minutes. No cycling, no loading phase, no timing precision beyond "30-60 minutes pre-bed" for sleep use.
Opportunity Cost (1.1/5.0). Glycine stacks cleanly with magnesium (bisglycinate or threonate), L-theanine, apigenin, collagen peptides, NAC, creatine, and standard sleep-stack ingredients. It does not displace any other sleep or longevity tool and does not compete for absorption pathways with common supplements. The only real-world opportunity cost is the minor caloric displacement (~12 kcal per 3 g serving), irrelevant at supplementation scale. Per v0.5 audience-vs-indication rules, this dimension is scored for the indicated population (adults seeking sleep, connective tissue, or healthspan support); for healthy lifters under 40 with no sleep complaints, opportunity cost is effectively neutral since glycine slots in alongside their existing stack.
Dependency/Withdrawal (1.0/5.0). Glycine acts as a biochemical substrate, not a drug. No receptor downregulation has been documented at the GlyR or NMDA sites with chronic supplementation, no tolerance development over months of daily use, and no withdrawal symptoms on abrupt cessation. Per the v0.5 dependency-vs-addiction framework, glycine represents the substrate-class floor: stopping produces no rebound, no craving, no autonomic or psychological withdrawal. The sleep benefit simply fades over the first few nights off the compound as plasma levels drop back to baseline.
Reversibility (1.0/5.0). Fully reversible. Plasma half-life of exogenous glycine is on the order of hours, and within 24-72 hours of stopping, all supplementation-dependent effects (sleep consolidation, GSH elevation above baseline, connective tissue substrate flux) return to pre-supplementation levels. No structural, epigenetic, or persistent metabolic changes have been documented from chronic glycine intake. This is the cleanest reversibility profile in the BioHarmony archive, shared only by electrolytes and a few other endogenous metabolites.
Verdict
✅ Best for: Adults 50+ seeking sleep consolidation, glutathione restoration, or sarcopenia protection (biggest documented response, 55% RBC glycine deficit). Vegans, vegetarians, and low-collagen diets (covers connective tissue synthesis gap). Shift workers and frequent travelers (3 g pre-bed restores sleep quality on off-cycle nights without sedation hangover). Schizophrenia patients on non-clozapine antipsychotics (SMD −1.12 on negative symptoms at 0.4-0.8 g/kg/day). Collagen peptide users (5 g co-dose corrects amino acid imbalance).
❌ Avoid if: You are taking clozapine for schizophrenia (hard contraindication, Tsai 2006 SMD +0.56 worsening). You have primary hyperoxaluria without confirmed B6 adequacy. You are pregnant or nursing (consult a prescriber; RCT data absent). Healthy lifters under 40 with no sleep complaints will get modest subjective return from glycine, though collagen and glutathione upside still apply.
Use Case Breakdown
The overall BioHarmony score reflects the intervention's primary evidence profile. These subratings are independent assessments per use case.
| Use Case | Score | Summary |
|---|---|---|
| ✅ Sleep Quality | 8.5 | Yamadera 2007 (n=19) and Bannai 2012 (n=10 PSG) show 5-6 min earlier SWS onset and improved subjective sleep at 3 g pre-bed. Stronger in older adults. |
| ✅ Geriatric / Aging Population | 8.5 | Elderly have 55% lower RBC glycine baseline (Sekhar 2011); strongest documented response population. Kumar 2021 GlyNAC effects measured specifically in older adults. |
| ✅ Antioxidant / Oxidative Stress | 8.0 | Rate-limiting substrate for glutathione synthesis; direct biochemistry. Díaz-Flores 2013 confirms 5 g/day reduces oxidative stress markers in metabolic syndrome. |
| ✅ Longevity / Lifespan | 8.0 | GlyNAC (Kumar 2021): GSH +225%, IL-6 −78%, grip strength +13% in 16 weeks. Awaits independent replication. |
| 💪 Healthspan | 7.8 | Sekhar 2023 36-week GlyNAC extension shows multiple aging hallmark reversal; single group, awaits replication. |
| 💪 Skin / Beauty | 7.8 | Collagen synthesis substrate; co-dose with collagen peptides supports skin elasticity endpoints. |
| 💪 Liver / Detoxification | 7.6 | Phase II conjugation substrate (glycine conjugation + bile acid conjugation); direct hepatic GSH restoration. |
| 💪 Sleep Architecture (Deep/REM) | 7.5 | Kawai 2015 thermoregulatory vasodilation mechanism + ~30% of users report vivid or cinematic dreams, consistent with altered REM structure. |
| 💪 Recovery / Repair | 7.5 | Connective tissue substrate plus sleep consolidation; athletes report subjective recovery benefit. |
| 💪 Mitochondrial | 7.2 | GlyNAC restores mitochondrial function via GSH repletion; Sekhar 2023 confirms over 36 weeks. |
| 💪 Injury Recovery | 7.2 | Collagen 33% glycine; direct substrate for tendon/ligament/cartilage repair. |
| 💪 Anti-Inflammatory | 7.0 | Kumar 2021: IL-6 dropped 78% with GlyNAC in older adults. Glycine alone weaker; the combination drives the signal. |
| 💪 Wound Healing | 7.0 | Collagen synthesis substrate supports wound closure; GSH supports oxidative stress management in healing tissue. |
| 💪 Bone / Joint Health | 7.0 | Bone matrix is ~30% collagen by mass; glycine supports both bone and cartilage synthesis. |
| 👍 Strength / Power | 6.8 | GlyNAC grip strength +13% in older adults (Kumar 2021); mechanism likely GSH-mediated muscle protein synthesis. |
| 👍 Gut Health / Microbiome | 6.8 | Glycine supports gut barrier integrity via glutathione and tight-junction redox regulation; animal data strong, human trials sparse. |
| 👍 Cellular Senescence | 6.5 | GSH restoration indirectly supports senescence-related redox balance; no direct senolytic data. |
| 👍 Methylation Support | 6.5 | Glycine is the acceptor for one-carbon units via GNMT; high-methionine diets drain glycine and supplementation supports methyl buffering (Lopez-Torres 2008). |
| 👍 Metabolic Health | 6.5 | Insulin sensitivity restored in Kumar 2021 GlyNAC cohort. Direct glycine data at 5 g/day shows oxidative-stress-mediated improvement. |
| 👍 Neuroprotection | 6.5 | GSH restoration is favorable in neurodegeneration models; no human RCTs in AD/PD. |
| 👍 Mood / Emotional Regulation | 6.5 | Partial GABA-A agonism and inhibitory neurotransmission; mechanistic basis solid but RCTs in non-schizophrenia populations sparse. |
| 👍 Anxiety | 6.5 | Inhibitory neurotransmission theoretically anxiolytic; no dedicated anxiety RCTs in non-clinical populations. |
| 👍 Stress / Resilience | 6.5 | Supports glutathione-mediated oxidative stress buffering; indirect HPA axis effect via sleep consolidation. |
| 👍 Hair / Nail Health | 6.5 | Structural collagen precursor; indirect support for hair and nail matrix. |
| 👍 Immune Function | 6.5 | GSH restoration supports immune cell function and redox signaling; indirect. |
| 👍 Blood Sugar / Glycemic Control | 6.2 | Pre-meal 5 g glycine modestly improves postprandial glucose handling; effect size small. |
| 👍 Circadian Rhythm / Chronobiology | 6.0 | Works through SCN-mediated thermoregulatory drop; indirect circadian support via sleep consolidation, not phase-shifting. |
| 👍 Telomere / DNA Repair | 6.0 | GSH supports DNA repair via oxidative damage reduction; Kumar 2021 reported reduced genotoxicity markers. |
| 👍 HRV / Vagal Tone / Autonomic Balance | 6.0 | Inhibitory neurotransmission supports parasympathetic tone via NMDA/GlyR modulation in brainstem; indirect HRV support. |
| 👍 Cardiovascular | 5.8 | Modest BP improvement in Díaz-Flores 2013; no hard cardiovascular endpoints. |
| ⚖️ Autophagy | 5.5 | Indirect via mitochondrial restoration; no direct autophagy flux data. |
| ⚖️ Heavy Metal / Toxin Burden | 5.5 | GSH is the primary mercury/heavy-metal chelator; glycine supports GSH pool. Indirect. |
| ⚖️ Energy / Fatigue | 5.5 | Indirect via sleep quality and GlyNAC-mediated mitochondrial restoration; no direct acute energy effect. |
| ⚖️ Body Composition / Fat Loss | 5.5 | Grip strength +13% in GlyNAC cohort reflects lean-mass support; no direct fat-loss signal. |
| ⚖️ Memory | 5.5 | GlyNAC supports cognitive function in aging (Kumar 2021); direct memory endpoints secondary. |
| ⚖️ Neuroplasticity | 5.5 | NMDA co-agonism at GluN1 site is central to LTP; mechanistic support but no direct RCT evidence for plasticity endpoints. |
| ⚖️ Flexibility / Mobility | 5.5 | Indirect via connective tissue integrity. |
| ⚖️ Muscle Growth / Hypertrophy | 5.5 | No direct hypertrophy signal; creatine substrate pathway is downstream but modest. |
| ⚖️ Kidney Function | 5.5 | Supports kidney function via GSH; primary hyperoxaluria is a theoretical concern (glyoxylate pathway) clinically irrelevant with adequate B6. |
| ⚖️ Chronic Pain Management | 5.5 | GlyR pharmacology suggests theoretical role in chronic pain; no dedicated pain RCTs. |
| ⚖️ Endurance / Cardio | 5.2 | No direct endurance signal; indirect via mitochondrial restoration in aged populations. |
| ⚖️ Cognition / Focus | 5.0 | Acute cognition signal weak outside sleep-restricted populations; Bannai 2012 showed next-day performance benefit after partial sleep restriction. |
| ⚖️ Traumatic Brain Injury | 5.0 | GSH support theoretically favorable post-injury; no direct TBI trials. |
| ⚖️ Depression | 5.0 | No direct depression evidence outside the schizophrenia context. |
| ⚖️ Hormonal / Endocrine | 5.0 | No direct hormonal signal outside sleep-mediated cortisol and growth-hormone modulation. |
| ⚖️ Pregnancy Safety | 5.0 | Endogenous demand rises in pregnancy but supplementation RCTs absent. Consult prescriber before use. |
| ⚖️ Respiratory | 5.0 | No direct respiratory evidence. |
| ⚖️ Eye / Vision Health | 5.0 | Retinal GSH support is theoretical; no clinical endpoints. |
| ⚖️ Cold / Heat Tolerance / Hormesis | 5.0 | Thermoregulatory mechanism in SCN; theoretical cold-adaptation support. |
| ⚖️ Acute Pain Relief | 5.0 | Inhibitory neurotransmission suggests theoretical role; human data sparse. |
| ○ Stem Cell Support | 4.5 | No direct stem cell evidence. |
| ○ Nerve Regeneration | 4.5 | No direct nerve regeneration evidence. |
| ○ Flow State / Peak Mental Performance | 4.5 | No direct flow-state evidence. |
| ○ Creativity / Divergent Thinking | 4.5 | No direct creativity evidence. |
| ○ Reaction Time / Coordination | 4.5 | No direct reaction-time evidence. |
| ○ Spiritual / Consciousness Expansion | 4.5 | No direct evidence; vivid-dream reports are anecdotal. |
| ○ Libido / Sexual Health | 4.5 | No direct evidence; indirect via sleep and stress. |
| ○ Fertility (Male) | 4.5 | No direct RCT evidence. |
| ○ Fertility (Female) | 4.5 | No direct RCT evidence. |
| ○ Pediatric Use | 4.5 | No RCT evidence in pediatric populations. |
| ○ VO2 Max | 4.5 | No direct VO2 evidence. |
| ○ Dental / Oral Health | 4.5 | No direct evidence. |
| ○ Lymphatic / Drainage | 4.5 | No direct evidence. |
| ○ Social Bonding / Empathy | 4.0 | No direct evidence. |
| ○ Hearing / Auditory | 4.0 | No direct evidence. |
| ○ Electromagnetic / Frequency Therapy | 4.0 | Not applicable. |
Frequently Asked Questions
How much glycine should I take for sleep?
Start with 3 g oral glycine 30-60 minutes before bed (Bannai 2012, Front Neurol, n=10: shortened slow-wave sleep onset by 5-6 minutes on PSG). Evaluate over 5-7 nights. Non-responders can escalate to 5 g. Single boluses above 9 g trigger GI discomfort in most users.
What is GlyNAC and how does it differ from glycine alone?
GlyNAC is a combined protocol of 100 mg/kg/day glycine plus 100 mg/kg/day N-acetylcysteine, split across meals for 16-24+ weeks (Kumar 2021, J Gerontol, n=24 older adults). Intracellular glutathione rose 225%, IL-6 dropped 78%, grip strength improved 13%. The combination restores both rate-limiting GSH substrates in aging; glycine alone produces a fraction of the effect.
Is glycine safe to take every night long-term?
Glycine is among the safest ingestible compounds studied; endogenous synthesis already produces ~3 g/day and dietary intake adds several grams (Razak 2017, Oxid Med Cell Longev). No organ toxicity has been documented at multi-gram daily intake in humans. The primary ceiling is GI tolerance above 9 g single boluses. Contraindicated only as an adjunct to clozapine (Tsai 2006).
What are the common side effects of glycine?
Most common: mild GI discomfort (loose stools, nausea) at single doses above 9 g, resolved with divided dosing. Approximately 30% of users report vivid or cinematic dreams, which can be experienced as a feature or a side effect. Occasional mild morning grogginess at 5 g+ pre-bed. No withdrawal, no rebound insomnia on cessation.
Who should NOT take glycine?
Hard contraindication: anyone taking clozapine for schizophrenia (Tsai 2006 meta: SMD +0.56 worsening of negative symptoms). Patients with primary hyperoxaluria should clear glycine supplementation with a specialist and ensure adequate B6 status. Pregnancy and nursing: consult a prescriber. No drug interactions documented outside the clozapine signal.
How fast does glycine work?
Sleep effects are measurable night one in responders; the thermoregulatory vasodilation mechanism (Kawai 2015, Neuropsychopharmacology) is acute after a single oral dose. GlyNAC-mediated longevity endpoints (GSH, IL-6, grip strength) require 16-24 weeks before clinical signals stabilize (Kumar 2021).
Does glycine help with collagen synthesis?
Glycine occupies every third residue of the collagen triple helix (33% of all amino acids in collagen). Co-dosing 5-15 g glycine with 15-20 g collagen peptides corrects the amino acid imbalance inherent to collagen peptides alone (which can transiently depress plasma tryptophan). Mechanistic basis is strong; dedicated human RCTs on collagen synthesis rates at supra-dietary glycine intake are limited.
What form of glycine should I buy?
Bulk pharma-grade glycine powder from a tested source, ~$20-30 per kg, is the rational form. Capsules are overpriced per gram (glycine is cheap in raw form). The compound dissolves instantly in water and tastes mildly sweet. Third-party-tested brands are preferred; contamination risk is low but quality varies.
How This Score Could Change
BioHarmony scores are living assessments. New research, regulatory changes, or personal context can shift the score up or down. These are the most likely scenarios that would change this intervention's rating.
| Scenario | Dimension shifts | New score |
|---|---|---|
| Independent GlyNAC replication lands | Evidence 3.5→4.3, Efficacy 3.0→3.8, Durability 2.0→2.3 | 8.5 / 10 (✅ Top-tier) |
| Industry-neutral sleep PSG RCT (n=200+) confirms Kawai mechanism in humans | Evidence 3.5→4.0 | 8.0 / 10 (✅ Top-tier) |
| GI tolerance caps real-world compliance below effective dose | Efficacy 3.0→2.3, Bioindividuality 3.8→3.0 | 7.0 / 10 (💪 Strong recommend, borderline) |
| Population-scale oxalate signal surfaces at multi-gram intake | Safety 1.2→2.5 | 7.2 / 10 (💪 Strong recommend) |
| Collagen stable-isotope tracer confirms supra-dietary glycine raises procollagen synthesis | Breadth 4.2→4.5, Bioindividuality 3.8→4.0 | 7.9 / 10 (💪 Strong recommend) |
| Head-to-head vs magnesium bisglycinate for sleep shows equivalence at lower cost | Efficacy 3.0→3.3 | 7.9 / 10 (💪 Strong recommend) |
Key Evidence Sources
- Kumar P, et al. 2021. Supplementing glycine and N-acetylcysteine (GlyNAC) in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, muscle strength, and cognition. J Gerontol A Biol Sci Med Sci 76(1):75-89. — Flagship RCT: n=24 older adults, 16 weeks, 100 mg/kg/day each. GSH +225%, IL-6 −78%, grip strength +13%.
- Sekhar RV, et al. 2023. GlyNAC supplementation in older adults improves multiple defects of aging. Clin Transl Med. — 36-week open-label extension confirming Kumar 2021. Single research group; no independent replication yet.
- Sekhar RV, et al. 2011. Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. Am J Clin Nutr 94(3):847-53. — Foundational mechanism paper. Elderly RBC glycine 218 μmol/L vs young 487 μmol/L (~55% lower).
- Yamadera W, et al. 2007. Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes. Sleep Biol Rhythms 5(2):126-31. — n=19, 3 g pre-bed, Ajinomoto-funded. St. Mary's Hospital Sleep Questionnaire improvement and reduced next-day fatigue.
- Bannai M, Kawai N. 2012. New therapeutic strategy for amino acid medicine: glycine improves the quality of sleep. J Pharmacol Sci 118(2):145-8. — n=10 partially sleep-restricted healthy males. 3 g glycine shortened latency to slow-wave sleep and improved next-day cognition on PSG.
- Kawai N, et al. 2015. The sleep-promoting and hypothermic effects of glycine are mediated by NMDA receptors in the suprachiasmatic nucleus. Neuropsychopharmacology 40(6):1405-16. — Mechanistic: 2 g/kg oral in rats increased cutaneous blood flow 11.3%. NMDA antagonists (AP5, CGP78608) abolished the effect. SCN lesion abolished it. GlyR (strychnine) did not.
- Tsai G, et al. 2006. Glutamatergic drugs as novel therapies for schizophrenia: meta-analysis. Schizophr Bull 32(4):762-74. — 29 RCTs, n=1,253. SMD −1.12 on negative symptoms with non-clozapine antipsychotics. SMD +0.56 HARM with clozapine (HARD contraindication).
- Zhao J, et al. 2024. Effects of glycine supplementation on sleep and cognitive outcomes: a systematic review. GeroScience. — Rated existing sleep RCTs serious-to-critical risk of bias. Flags Ajinomoto funding concentration.
- Díaz-Flores M, et al. 2013. Oral supplementation with glycine reduces oxidative stress in patients with metabolic syndrome, improving their systolic blood pressure. Can J Physiol Pharmacol 91(10):855-60. — 5 g/day × 3 months. Oxidative stress markers reduced, systolic BP modestly improved.
- Razak MA, et al. 2017. Multifarious beneficial effects of nonessential amino acid, glycine: a review. Oxid Med Cell Longev 2017:1716701. — Breadth-of-benefits review covering GSH, collagen, sleep, insulin sensitivity, inflammation, detoxification.
- McCarty MF, O'Keefe JH, DiNicolantonio JJ. 2018. Dietary glycine is rate-limiting for glutathione synthesis and may have broad potential for health protection. Ochsner J 18(1):81-7. — Integrative review arguing glycine is rate-limiting for GSH synthesis at typical dietary intakes.
- Lopez-Torres M, Barja G. 2008. Lowered methionine ingestion as responsible for the decrease in rodent mitochondrial oxidative stress in protein and dietary restriction: possible implications for humans. Biochim Biophys Acta 1780(11):1337-47. — Mechanism context: high-methionine diets drain glycine via one-carbon metabolism, widening the functional deficit.
Other interventions for Sleep Quality
See all ratings →📊 How BioHarmony scoring works
BioHarmony translates a weighted expected-value calculation into a reader-facing 0–10 score. 5.0 is neutral (benefits and risks balance). Above 5 = benefits outweigh risks; below 5 = risks outweigh benefits.
Harm-type downsides (safety risk, side effects, reversibility, dependency) carry a 1.4× precautionary multiplier. Harm weighs more than benefit. Opportunity-type downsides (financial cost, time/effort, opportunity cost) are subtracted at face value.
Use case subratings are independent assessments of how well the intervention addresses specific health goals. They are not components of the overall score. Each subrating reflects the scorer's judgment based on use-case-specific evidence, safety, and effect sizes.
Every dimension is evaluated on a 1–5 scale, and the baseline (1) is subtracted before weighting. A perfect intervention with zero downsides contributes zero penalty rather than a residual floor, so top-tier scores are actually reachable.
EV = Upside − Downside
EV = 2.430 − 0.180 = 2.250
EV ranges from −5 to +5. Adding 7 shifts to 2–12, dividing by 12 normalizes to 0–1, then ×10 gives the 0–10 score.
Score = ((2.250 + 7) / 12) × 10 = 7.7 / 10
Further reading
