Evidence Level
Limited
6 Clinical Trials
5 Documented Benefits
2/5 Evidence Score

Glycine is a non-essential amino acid found in protein-rich foods and made by the body; it is the most abundant amino acid in collagen and acts as a neurotransmitter. As a dietary supplement, it is mainly used for sleep, where three small trials of 3 grams at bedtime, all linked to the glycine seller Ajinomoto, reported better subjective sleep quality. Small trials have looked at blood sugar markers, and glycine combined with NAC (GlyNAC) has been studied in older adults, but no human trial has tested glycine alone for skin or joints.

Studied Dose 3 g at bedtime in the sleep trials; 15 g/day in one small metabolic trial; 30 to 60 g/day only in supervised psychiatric research.
Active Compound Glycine (free amino acid)

Benefits

Subjective Sleep Quality

In three small Japanese crossover trials (about 19, 11 and 7 people), 3 grams before bed improved self-rated sleep quality; one found faster sleep onset on brain-wave recordings and one found less next-day fatigue, with no significant difference in sleepiness. All three were linked to Ajinomoto, which sells glycine for sleep, and we found no independent repeat.

Blood Sugar Markers

In 9 healthy people, glycine taken with sugar cut the blood glucose response by more than half in a single test, and small Mexican trials in type 2 diabetes and metabolic syndrome reported lower lab markers. A genetic study of 80,003 people suggests insulin resistance may lower glycine rather than the reverse.

Collagen Building Block

Glycine makes up about a third of collagen. Whether extra glycine changes joint or skin collagen in people has not been tested in a published human trial.

Glutathione (with NAC)

Glycine combined with N-acetylcysteine (GlyNAC) raised glutathione and improved aging markers in small trials from one Baylor group, which holds a patent licensed to Nestle; a larger Nestle trial found no significant difference in its main glutathione measure. These results cannot be credited to glycine alone.

High-Dose Psychiatric Research

At about 60 grams a day under medical supervision, glycine added to some antipsychotics improved symptoms in small crossover trials, but the largest trial (157 patients) found no significant difference from placebo. These are drug-level research doses, not supplement use.

Mechanism of action

1

Neurotransmitter Role

Glycine is an inhibitory neurotransmitter in the central nervous system, acting on glycine receptors to hyperpolarize neurons, reducing neuronal excitability and promoting calmness.

2

Thermoregulation

In rats, oral glycine lowered core body temperature by widening skin blood vessels, acting through NMDA receptors in the suprachiasmatic nucleus, the brain's clock region; this has not been confirmed in peer-reviewed human studies.

3

NMDA Receptor Modulation

Glycine is a co-agonist at NMDA receptors, enhancing glutamatergic signaling critical for synaptic plasticity, learning, and memory.

4

Inhibitory Signaling

Its action on glycine receptors reduces neuronal excitability in the spinal cord and brainstem; no controlled trial of glycine for depression or anxiety at supplement doses was found.

5

Collagen Synthesis

Glycine occupies every third position of the collagen triple helix, about a third of its amino acids.

6

Anti-inflammatory Effects

In cell and animal studies, glycine dampens pro-inflammatory cytokines such as TNF-alpha; a hemodialysis trial found no significant effect on cytokines.

7

Insulin Sensitivity

Glycine may support insulin signaling, possibly through glutathione synthesis; human evidence is limited to small lab-marker trials.

8

Anti-inflammatory

It inhibits NF-κB activation, reducing systemic inflammation linked to metabolic disorders.

9

Detoxification

Glycine is a precursor to glutathione, a key antioxidant that neutralizes reactive oxygen species and supports liver detoxification.

10

Cytoprotection

In animal studies, glycine reduced oxidative damage in liver cells after alcohol or toxins; no human liver trial of glycine alone was found.

11

Protein Synthesis

Glycine supports mTOR signaling and provides building blocks for muscle protein synthesis, counteracting muscle breakdown.

Clinical trials

1
Glycine Before Bed in Sleep-Restricted Volunteers: Crossover Trial

Randomized, single-blind crossover trial: 3 g glycine or placebo 30 minutes before bed during 3 nights of sleep cut by 25%. Volunteers were full-time Ajinomoto employees and 3 of 5 authors worked for Ajinomoto. (Bannai et al. 2012, Front Neurol)

10 healthy men enrolled, 7 analyzed.

Next-day fatigue on a visual scale was lower on glycine (p = 0.022) and reaction time improved; sleepiness showed no significant difference (p = 0.098). Sleep itself was tracked only by sleep logs.

2
GlyNAC (Glycine + N-Acetylcysteine) in Older Adults: Randomized Trial

Double-blind, placebo-controlled trial in 24 older adults (mean age about 71) randomized to GlyNAC or an alanine placebo for 16 weeks, plus 12 young adults given GlyNAC for 2 weeks. Dose: 100 mg/kg/day each of glycine and NAC. Outcomes: glutathione, oxidative stress, mitochondrial markers, physical function, body composition. (J Gerontol A Biol Sci Med Sci, 2023)

24 older adults (12 GlyNAC, 12 placebo) plus 12 young adult comparators. 16-week intervention.

Reported improvements in glutathione, oxidative stress, mitochondrial markers, inflammation, insulin resistance, endothelial function, gait speed and body composition, mostly as within-group changes; cognition was not measured. The arms differed by sex (8 men in GlyNAC vs 4 in placebo). Small sample, single research group (Sekhar lab at Baylor); Baylor holds a GlyNAC patent licensed to Nestle Health Science. Every result reflects glycine plus NAC, not glycine alone.

3
GlyNAC Dose-Finding Clinical Trial in Older Adults

Randomized controlled trial in 114 healthy older adults receiving GlyNAC at low (2.4 g/day), medium (4.8 g/day), or high (7.2 g/day) doses for 2 weeks. Outcomes: glutathione redox status, oxidative damage, tolerability. (Lizzo/Migliavacca 2022, Front Aging)

114 healthy older adults. 2-week dose-finding.

Primary endpoint negative: over the 2-week intervention, GlyNAC did not significantly raise total glutathione or the glutathione redox ratio in the overall cohort. Only a post-hoc subset with high baseline oxidative stress and low baseline glutathione, on the medium or high dose, showed increased glutathione generation. Well-tolerated across doses. Because this trial was run by Nestle, which licenses GlyNAC patents, rather than by the Baylor group, its negative primary result tempers rather than confirms the glutathione-raising claims from the single-group Sekhar GlyNAC studies.

4
Enteral Glycine for Severe COVID-19: Clinical Trial

Open-label, controlled trial in 56 patients with severe COVID-19 requiring mechanical ventilation receiving enteral glycine vs standard care. Outcomes: clinical recovery, ICU outcomes, mortality. (2024 Mexican trial)

56 severe COVID-19 ICU patients.

Primary endpoint negative: enteral glycine did not improve major clinical outcomes (mortality, ventilator-free days, ICU LOS) in severe COVID-19. Negative finding important; extrapolating GlyNAC anti-aging signals to acute critical illness was not supported.

5
Oral Glycine in Cystic Fibrosis: Small Crossover Trial

Double-blind crossover trial in 13 people with cystic fibrosis aged 6 to 23 taking oral glycine 0.5 g/kg/day or placebo for 8 weeks. Outcomes: symptom score, spirometry (FEV1), inflammatory markers. (Vargas et al. 2017, BMC Pulm Med)

13 people with CF aged 6 to 23, crossover.

Symptom scores and lung function measures improved on glycine versus placebo; inflammatory marker changes were mostly not significant. A small pilot only, at a supervised dose far above supplement amounts; modern CF care relies on CFTR modulators, and glycine is not a substitute.

6
High-Dose Glycine Adjuvant for Treatment-Resistant Schizophrenia: Crossover Clinical Trial

Double-blind, placebo-controlled crossover trial in 22 patients with treatment-resistant schizophrenia receiving high-dose glycine (0.8 g/kg/day, about 60 g for a 75 kg adult) added to antipsychotics for 6 weeks. (Heresco-Levy 1999, Arch Gen Psychiatry)

22 treatment-resistant schizophrenia patients. Crossover.

Negative symptoms and total symptom scores improved versus placebo. Context: in the largest trial, CONSIST (157 patients), neither glycine nor D-cycloserine beat placebo, and added to clozapine glycine did not help and may have worsened positive symptoms. Modern treatment has not adopted high-dose glycine; these are drug-level research doses.

Side effects and drug interactions

Common Potential side effects

Gastrointestinal Issues:: Mild nausea, upset stomach or loose stools, mostly at high doses; in a 60 g/day trial, people dropped out over taste and nausea. People taking 3 grams at bedtime rarely report digestive upset.
Drowsiness or Sedation:: Glycine is taken at bedtime for sleep; a Russian stroke trial of sublingual glycine reported slight sedation in 4.5% of patients, so avoid driving if it makes you drowsy.

Important Drug interactions

Clozapine: in small trials, high-dose glycine (30 to 60 g/day) added to clozapine did not improve symptoms, and one pooled analysis found positive symptoms worsened. People taking clozapine should check with their prescriber before using glycine.
NMDA receptor antagonists (ketamine, memantine, dextromethorphan); glycine co-agonism at NMDA receptors may modulate effects of NMDA antagonists; complex interaction
Other prescription medicines: no human interaction studies at 3 g were found; ask a pharmacist if you take sedatives or other prescription drugs.

Frequently asked questions about Glycine

How much glycine should I take?

For sleep, the trials used 3 grams taken 30 to 60 minutes before bed. It is a mildly sweet powder that dissolves easily in water.

Does glycine help with sleep?

Three small Japanese trials, all linked to the glycine seller Ajinomoto, found that about 3 grams before bed improved self-rated sleep quality, and one found faster sleep onset on brain-wave recordings. No independent group has repeated them.

When should I take glycine?

For sleep, take about 3 grams 30 to 60 minutes before bed, as in the trials.

Is glycine safe?

At 3 grams a day it is generally well tolerated, with occasional mild digestive upset at higher doses. People taking clozapine should ask their prescriber first, and it has not been studied as a supplement in pregnancy.

What is Glycine?

Glycine is a non-essential amino acid found in protein-rich foods and made by the body; it is the most abundant amino acid in collagen and acts as a neurotransmitter.

What is Glycine used for?

Glycine is researched primarily for Muscle & Recovery and Sleep Health. In three small Japanese crossover trials (about 19, 11 and 7 people), 3 grams before bed improved self-rated sleep quality; one found faster sleep onset on brain-wave recordings and one found less next-day fatigue, with no significant diffe…

Does Glycine interact with any medications?

Possible interactions include: Clozapine: in small trials, high-dose glycine (30 to 60 g/day) added to clozapine did not improve symptoms, and one pooled analysis found positive symptoms worsened. People taking clozapine should check with their prescriber before using glycine. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Glycine?

NutraSmarts rates the evidence for Glycine as Limited (2 out of 5). It is backed by 6 study summaries and 14 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(14 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Heresco-Levy U, Javitt DC, Ermilov M, Mordel C, Silipo G, Lichtenstein M. Efficacy of high-dose glycine in the treatment of enduring negative symptoms of schizophrenia. Arch Gen Psychiatry. 1999;56(1):29-36. doi: 10.1001/archpsyc.56.1.29.PubMedUsed to support: 6-week double-blind placebo-controlled crossover trial in 22 patients with treatment-resistant schizophrenia: high-dose glycine (0.8 g/kg/day) added to ongoing antipsychotic medication significantly reduced negative symptoms (avolition, blunted affect) vs placebo. Mechanism: NMDA glycine-modulatory-site agonism. Directly matches the page's trial card #5; replication has been mixed.
  2. Meléndez-Hevia E, De Paz-Lugo P, Cornish-Bowden A, Cárdenas ML. A weak link in metabolism: the metabolic capacity for glycine biosynthesis does not satisfy the need for collagen synthesis. J Biosci. 2009;34(6):853-72. doi: 10.1007/s12038-009-0100-9.PubMedUsed to support: Theoretical metabolic analysis arguing that glycine synthesis may fall short of collagen needs; not a human trial, and no trial has tested glycine for joints or skin.
  3. Bannai M, Kawai N, Ono K, Nakahara K, Murakami N. The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers. Front Neurol. 2012;3:61. doi: 10.3389/fneur.2012.00061.PubMedUsed to support: Single-blind crossover in 7 analyzed men (Ajinomoto employees) sleep-restricted to 75% of usual sleep for 3 nights: 3 g glycine before bed lowered next-day fatigue on a visual scale (p = 0.022); sleepiness showed no significant difference (p = 0.098). Three of five authors worked for Ajinomoto.
  4. Kawai N, Sakai N, Okuro M, Karakawa S, Tsuneyoshi Y, Kawasaki N, Takeda T, Bannai M, Nishino S. The sleep-promoting and hypothermic effects of glycine are mediated by NMDA receptors in the suprachiasmatic nucleus. Neuropsychopharmacology. 2015;40(6):1405-16. doi: 10.1038/npp.2014.326.PubMedUsed to support: Mechanistic study: oral glycine induced NREM sleep and shortened NREM sleep latency with concurrent core temperature decrease. Pretreatment with NMDA receptor antagonists (AP5, CGP78608) blocked the cutaneous blood flow increase from glycine; confirming NMDA-mediated thermoregulatory and sleep-promoting actions in the suprachiasmatic nucleus.
  5. Razak MA, Begum PS, Viswanath B, Rajagopal S. Multifarious Beneficial Effect of Nonessential Amino Acid, Glycine: A Review. Oxid Med Cell Longev. 2017;2017:1716701. doi: 10.1155/2017/1716701.PubMedUsed to support: Comprehensive review of glycine's roles across metabolic disorders (cardiovascular, inflammation, obesity, diabetes), sleep quality, neurological function, and as precursor for creatine, glutathione, haem, purines, and porphyrins. Backs the page's framing of glycine as a multi-purpose amino acid with applications spanning metabolic health, sleep, and antioxidant support.
  6. Kumar P, Liu C, Hsu JW, Chacko S, Minard C, Jahoor F, Sekhar RV. Glycine and N-acetylcysteine (GlyNAC) supplementation in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, muscle strength, and cognition: Results of a pilot clinical trial. Clin Transl Med. 2021;11(3):e372. doi: 10.1002/ctm2.372.PubMedUsed to support: 24-week open-label pilot with no placebo group in 8 older and 8 young adults: GlyNAC raised glutathione and improved oxidative stress, insulin resistance, strength and other markers, which declined after stopping. Results reflect glycine plus NAC.
  7. Kumar P, Liu C, Suliburk J, Hsu JW, Muthupillai R, Jahoor F, Minard CG, Taffet GE, Sekhar RV. Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial. J Gerontol A Biol Sci Med Sci. 2023;78(1):75-89. doi: 10.1093/gerona/glac135.PubMedUsed to support: 16-week double-blind RCT in 24 older adults (mean age about 71), GlyNAC 100 mg/kg/day each of glycine and NAC vs alanine placebo: within-group gains in glutathione, oxidative stress, mitochondrial markers, gait speed and strength; cognition not measured; single research group whose institution holds a GlyNAC patent licensed to Nestle.
  8. Vargas MH, Chávez J, Del-Razo-Rodríguez R, Muñoz-Perea C, Romo-Domínguez KJ, Báez-Saldaña R, Rumbo-Nava U, Guerrero-Zúñiga S. Glycine by enteral route does not improve major clinical outcomes in severe COVID-19: a randomized clinical pilot trial. Sci Rep. 2024;14(1):11566. doi: 10.1038/s41598-024-62321-7.PubMedUsed to support: Randomized pilot in severe COVID-19 patients on mechanical ventilation: 0.5 g/kg/day enteral glycine did not improve mortality (63.6% glycine vs 52.2% control), ventilator-free days, ICU length of stay, or other major outcomes. Important negative trial that constrains extrapolation of GlyNAC anti-aging signals to acute critical illness. Matches the page's trial card #2.
  9. Lizzo G, Migliavacca E, Lamers D, Frezal A, Corthesy J, Vinyes-Pares G, Bosco N, Karagounis LG, Hovelmann U, Heise T, von Eynatten M, Gut P. A Randomized Controlled Clinical Trial in Healthy Older Adults to Determine Efficacy of Glycine and N-Acetylcysteine Supplementation on Glutathione Redox Status and Oxidative Damage. Front Aging. 2022;3:852569. doi: 10.3389/fragi.2022.852569.PubMedUsed to support: Nestle-run (patent licensee) 2-week RCT in 114 healthy older adults testing GlyNAC at 2.4, 4.8, or 7.2 g/day. The trial MISSED its primary endpoint: GlyNAC did not significantly increase total glutathione or the glutathione redox ratio in the overall cohort; only a post-hoc subset with high oxidative stress and low baseline glutathione (medium/high dose) showed increased glutathione. Provides the source for trial card #3 and corrects its overstated 'dose-dependent glutathione elevation' framing.
  10. Singh SP, Singh V. Meta-analysis of the efficacy of adjunctive NMDA receptor modulators in chronic schizophrenia. CNS Drugs. 2011;25(10):859-85. doi: 10.2165/11586650-000000000-00000.PubMedUsed to support: Meta-analysis: glycine added to clozapine worsened positive symptoms (SMD +0.56); benefit only with other antipsychotics.
  11. Potkin SG, Jin Y, Bunney BG, Costa J, Gulasekaram B. Effect of clozapine and adjunctive high-dose glycine in treatment-resistant schizophrenia. Am J Psychiatry. 1999;156(1):145-7. doi: 10.1176/ajp.156.1.145.PubMedUsed to support: Trial of 30 g/day glycine added to clozapine: glycine was not effective; placebo group improved more.
  12. Buchanan RW, Javitt DC, Marder SR, Schooler NR, Gold JM, McMahon RP, Heresco-Levy U, Carpenter WT. The Cognitive and Negative Symptoms in Schizophrenia Trial (CONSIST): the efficacy of glutamatergic agents for negative symptoms and cognitive impairments. Am J Psychiatry. 2007;164(10):1593-602. doi: 10.1176/appi.ajp.2007.06081358.PubMedUsed to support: CONSIST trial, 157 patients: glycine not significantly different from placebo on negative symptoms or cognition.
  13. Wittemans LBL, Lotta LA, Oliver-Williams C, Stewart ID, Surendran P, Karthikeyan S, Day FR, Koulman A, Imamura F, Zeng L, Erdmann J, Schunkert H, Khaw KT, Griffin JL, Forouhi NG, Scott RA, Wood AM, Burgess S, Howson JMM, Danesh J, Wareham NJ, Butterworth AS, Langenberg C. Assessing the causal association of glycine with risk of cardio-metabolic diseases. Nat Commun. 2019;10(1):1060. doi: 10.1038/s41467-019-08936-1.PubMedUsed to support: Genetic study of 80,003 people: insulin resistance appears to lower glycine; weaker evidence for glycine lowering diabetes risk.
  14. Soh J, Raventhiran S, Lee JH, Lim ZX, Goh J, Kennedy BK, Maier AB. The effect of glycine administration on the characteristics of physiological systems in human adults: A systematic review. Geroscience. 2024;46(1):219-239. doi: 10.1007/s11357-023-00970-8.PubMedUsed to support: Systematic review: glycine sleep studies in healthy people were small with a high risk of bias.