Supplements

Glycine

Updated · 31 sources · Editorial policy

Glycine is the simplest amino acid. The body makes it from other nutrients and also gets it from food, especially from collagen-rich foods such as gelatin. It works as a building block for proteins (above all collagen), as a raw material for glutathione, creatine and heme, and as a signaling molecule in the brain and spinal cord.

As a supplement, glycine is mostly taken for sleep, usually 3 g before bed, and as half of “GlyNAC,” a glycine plus N-acetylcysteine combination studied in older adults. The most important fact is how thin the human evidence is. The sleep claim rests on three small Japanese trials with 7–19 analyzed participants each, run by one research group. A 2024 systematic review rated the sleep studies as small and at high risk of bias (Soh et al., GeroScience 2024).

This page summarizes what the clinical trials, systematic reviews and US regulations report. It is for education only and is not medical advice.

Property Detail
Class Non-essential amino acid; inhibitory neurotransmitter and co-agonist at NMDA glutamate receptors
Chemistry 2-aminoacetic acid, C2H5NO2, 75.07 g/mol
Forms Oral powder or capsules (supplement); 1.5% sterile irrigation solution (prescription, urologic surgery); ingredient of IV amino acid nutrition
Studied oral doses 3 g before bedtime (sleep trials); 15 g/day (metabolic trials); up to 0.8 g/kg/day (schizophrenia trials)
Half-life No oral figure found; after IV infusion, apparent half-life of 26–245 min, rising with dose
GlyNAC Glycine plus N-acetylcysteine, studied as glutathione precursors; small trials with mixed results
US status Amino acids are dietary supplement ingredients; FDA does not regard glycine added to conventional food as GRAS (since 1971)
WADA Not on the 2026 Prohibited List

What it is

Glycine’s side chain is a single hydrogen atom, which makes it the smallest amino acid (PubChem). Because of this, it has no separate L- and D- forms. “L-glycine” on a label is ordinary glycine.

It has several distinct jobs in the body:

  • Collagen. The tight packing of collagen’s triple helix requires glycine at every third position of the chain. This gives the repeating “Xaa-Yaa-Gly” pattern (Shoulders & Raines, Annu Rev Biochem 2009). This is why collagen and gelatin are rich glycine sources; the collagen peptides page covers those products.
  • Glutathione. Glutathione, the main antioxidant made inside cells, is built from glutamate, cysteine and glycine. This is the basis for pairing glycine with NAC, a cysteine source. The glutathione page covers glutathione itself.
  • Other molecules. Glycine is also a precursor of creatine, heme, purines and porphyrins (Razak et al., Oxid Med Cell Longev 2017).
  • Nerve signaling. Glycine acts as an inhibitory neurotransmitter through its own glycine receptors. It is also a required co-agonist at NMDA receptors, a type of excitatory glutamate receptor (Bannai & Kawai, J Pharmacol Sci 2012).

Betaine, sold as TMG, is glycine with three methyl groups attached. It is a different compound with different uses.

Is glycine really “non-essential”?

Glycine is classed as non-essential because the body can make it, mainly from serine. A 2009 theoretical analysis argued that this is not enough. It estimated that an adult makes about 3 g/day and eats 1.5–3.0 g/day, which may fall about 10 g/day short of total needs, mostly for collagen (Meléndez-Hevia et al., J Biosci 2009). This is a calculation from published metabolic fluxes, not a clinical finding. No trial has shown that extra glycine improves collagen-related outcomes in healthy people.

How it works in the body

Oral glycine is absorbed and raises blood glycine levels. A 2026 scoping review found 14 human trials of glycine, collagen or other glycine-containing supplements, which generally increased circulating glycine, with some sign of a dose effect (Fan et al., J Diet Suppl 2026). In a 2025 study, 19 adults with severe obesity took 100 mg/kg/day for two weeks, and plasma glycine rose significantly (Tan et al., Sci Rep 2025).

We found no published elimination half-life for oral glycine. The best kinetic data come from intravenous infusions and from glycine absorbed during prostate surgery (Hahn, Urol Res 1993):

Group Glycine amount Apparent half-life
17 patients during transurethral prostate surgery, plus 18 volunteers given IV infusions 10–91 g (patients); 15–22 g (volunteers) 26–245 min, rising in direct proportion to the dose

These are very large, mostly intravenous amounts. They do not tell you how long a 3 g oral dose lasts.

How glycine might affect sleep

The proposed mechanism comes mainly from rat studies by the same research group as the human sleep trials. In rats, oral glycine raised glycine in blood and cerebrospinal fluid, increased blood flow to the skin and lowered core body temperature (Bannai & Kawai, J Pharmacol Sci 2012). A fall in core temperature is part of normal sleep onset.

A 2015 rat study traced this effect to NMDA receptors in the suprachiasmatic nucleus (the brain’s master clock). Oral glycine shortened the time to non-REM sleep and lowered core temperature. Destroying the suprachiasmatic nucleus abolished both effects. Blocking NMDA receptors prevented the rise in skin blood flow caused by glycine injected into the brain (Kawai et al., Neuropsychopharmacology 2015). In another rat experiment, a large oral dose of glycine (2 g/kg) did not change blood melatonin levels (Bannai et al., Front Neurol 2012). The proposed mechanism therefore differs from that of melatonin.

Regulatory status

  • Dietary supplement. US law lists “an amino acid” as a dietary ingredient, so glycine can be sold as a dietary supplement (21 U.S.C. 321(ff)).
  • Conventional food. In 1971 FDA stopped regarding glycine and its salts as generally recognized as safe (GRAS) when added to human food. It cited reports of adverse effects in animals fed high levels and a rising dietary intake (21 CFR 170.50). Glycine is now permitted as a food additive only for narrow technical uses, such as masking saccharin’s aftertaste in beverages at no more than 0.2% (21 CFR 172.812).
  • Prescription irrigation fluid. A sterile 1.5% glycine solution is labeled as an irrigating fluid during transurethral urologic surgery. It is not for injection or oral use (Baxter label, DailyMed).
  • Sport. Glycine is not named on the WADA 2026 Prohibited List.

What the research shows

Sleep

Three small human trials tested 3 g of glycine before bedtime. All came from one Japanese research group. Its members included scientists at Ajinomoto Co. (Bannai et al., Front Neurol 2012). Trial details below are from the original reports and from the table of a 2024 systematic review (Soh et al., GeroScience 2024):

Study Participants Design and dose Reported findings
Inagawa et al., Sleep Biol Rhythms 2006 19 women dissatisfied with their sleep Crossover vs flavored placebo; 3 g 1 h before bed for 4 days Better subjective sleep quality on questionnaires
Yamadera et al., Sleep Biol Rhythms 2007 11 adults (73% women) with ongoing unsatisfactory sleep Randomized crossover vs flavored placebo; 3 g 1 h before bed for 2 nights; polysomnography (overnight sleep recording) Better subjective sleep quality and sleep efficiency; shorter time to fall asleep and to reach slow-wave sleep; no change in sleep architecture; less daytime sleepiness; better memory-recognition scores
Bannai et al., Front Neurol 2012 10 healthy men (company employees) without sleep complaints; 7 analyzed Randomized, single-blind crossover; sleep cut by 25% for 3 nights; 3 g 30 min before bed Less daytime fatigue (significant) and a trend toward less sleepiness; better psychomotor vigilance test performance

In the 2012 trial, 1 participant dropped out and 2 were excluded for taking medication, which left 7 (Bannai et al., Front Neurol 2012).

How to read this evidence:

  • Very small and short. The trials analyzed 7–19 people for 2–4 nights each. None tested use for longer than 4 nights.
  • High risk of bias. The 2024 systematic review concluded that the sleep findings in healthy people came from “small sample sizes with a high risk of bias.” None of the crossover trials it assessed had a low overall risk of bias (Soh et al., GeroScience 2024).
  • No independent replication. A 2026 scoping review again found only these 3 glycine sleep trials. All reported a benefit on at least one sleep outcome, and the authors called for larger trials with standard sleep measures (Fan et al., J Diet Suppl 2026).

For comparison, sleep trials of magnesium, L-theanine and melatonin are covered on their own pages.

Glycine and collagen as a source of glycine

Because glycine fills every third position in collagen’s helix, some researchers suggest that collagen’s reported sleep effects may come from its glycine. The 2026 scoping review found 1 placebo-controlled collagen trial with fewer awakenings on sleep recordings, and 1 with lower fatigue scores. It concluded that glycine is a plausible mechanism, but that this has “not been directly tested” (Fan et al., J Diet Suppl 2026). See the collagen peptides page for those products.

GlyNAC (glycine plus N-acetylcysteine)

GlyNAC supplies two of glutathione’s three building blocks. Most of the human data come from one group at Baylor College of Medicine:

Study Design Participants Main reported results
Sekhar et al., AJCN 2011 Open-label, 2 weeks of cysteine plus glycine 8 older and 8 younger adults In older adults, red-cell glutathione rose 94.6% and glutathione synthesis rose; markers of oxidative stress fell
Kumar et al., Biomedicines 2020 Open-label, 12 weeks, then 8 weeks off 8 people with HIV and 8 uninfected controls (controls not supplemented) Improvements in oxidative stress, mitochondrial, strength and cognition measures; benefits receded after stopping
Kumar et al., Clin Transl Med 2021 Open-label, 24 weeks, then 12 weeks off; glycine 1.33 mmol/kg/day plus cysteine 0.81 mmol/kg/day as NAC 8 older adults aged 71–80; 8 young adults studied once for comparison See table below; benefits declined after stopping
Sekhar, Antioxidants 2022 Open-label, 14 days 10 adults with type 2 diabetes; 10 unsupplemented controls Insulin resistance fell 22%; mitochondrial fat oxidation rose 30%
Kumar et al., J Gerontol A 2023 Randomized, placebo-controlled, 16 weeks 24 older adults (12 GlyNAC, 12 alanine placebo); 12 young adults given GlyNAC for 2 weeks Authors report that GlyNAC, not placebo, improved glutathione, oxidative stress, mitochondrial function, inflammation, insulin resistance, physical function and other measures

In the 24-week pilot, the older adults’ results were as follows (Kumar et al., Clin Transl Med 2021):

Measure (mean) Young adults Older adults, baseline After 24 weeks of GlyNAC 12 weeks after stopping
Red-cell total glutathione (mmol/L RBC) 1.8 0.8 1.6 0.9
Gait speed (m/s) 1.4 1.0 1.5 1.2
6-minute rapid walk (m) 723 546 603 562
Waist circumference (m) 0.78 0.91 0.86 0.88

The only randomized trial from a different research group did not confirm the main biochemical effect. It was run by Nestlé, which markets a GlyNAC product, and randomized 117 healthy adults aged 60–85 to placebo or GlyNAC at 2.4, 4.8 or 7.2 g/day (equal parts glycine and NAC) for 2 weeks (Lizzo et al., Front Aging 2022):

  • Primary outcome missed. No dose raised whole-blood total glutathione compared with placebo (7.2 g arm vs placebo, p = 0.28).
  • Possible subgroup effect. In a post-hoc analysis, people with high oxidative stress and low baseline glutathione who took the two higher doses did show increased glutathione. Post-hoc findings like this need confirmation.
  • Safety. No serious adverse effects were reported, and no one stopped because of side effects.

Taken together, the GlyNAC evidence is promising but early:

  • Small and mostly uncontrolled. Apart from the Nestlé trial, the studies enrolled 8–24 supplemented people, and most had no placebo group.
  • One research group. The positive findings come mainly from a single team.
  • Outcome questions. The registered primary outcome of the 16-week randomized trial was muscle glutathione concentration (NCT01870193). The published abstract reports a broad set of outcomes.
  • Not replicated. The only trial from another group lasted 2 weeks and did not reproduce the main glutathione result.

The NAC page covers NAC on its own, including its risks.

Other claimed uses

Use Best human evidence Evidence level
Schizophrenia (negative symptoms), added to antipsychotics Small crossover trial of 17 patients: 0.8 g/kg/day for 6 weeks cut negative symptoms by 23% (Heresco-Levy et al., Biol Psychiatry 2004). Cochrane review: glycine and D-serine moderately reduced negative symptoms (SMD −0.66, 95% CI −1.0 to −0.3) but results were inconsistent (Tuominen et al., Cochrane 2006). The largest trial, CONSIST (157 patients, 16 weeks), found no benefit over placebo (Buchanan et al., Am J Psychiatry 2007) Mixed; largest trial negative
Obsessive-compulsive disorder 24 patients randomized to placebo or glycine titrated to 60 g/day; only 14 could be evaluated because of dropouts. The result did not reach significance (p = 0.053) (Greenberg et al., J Psychiatr Res 2009) Very weak
Type 2 diabetes 74 patients allocated to glycine (5 g three times daily) or placebo for 3 months: lower HbA1c and some inflammatory markers with glycine (Cruz et al., J Endocrinol Invest 2008; dose per Soh et al. 2024) Single small trial
Metabolic syndrome 60 patients, 15 g/day or placebo for 3 months: a lipid-peroxidation marker fell 25%; systolic blood pressure fell only in men (Díaz-Flores et al., Can J Physiol Pharmacol 2013) Single small trial
Severe obesity and fatty liver markers 19 adults, 100 mg/kg/day for 2 weeks with no control group: no weight change; lower triglycerides and liver enzymes; glutathione unchanged (Tan et al., Sci Rep 2025) Uncontrolled pilot
Strength and muscle recovery One dose of 0.3 g/kg had no effect on strength in 6 resistance-trained adults. 30 g/day for 14 days before a marathon did not prevent muscle injury. In a crossover trial in hemodialysis patients with protein-energy wasting, 14 g/day for 4 months (vs BCAA) was reported to improve handgrip strength and fat-free mass index (Soh et al., GeroScience 2024) No support in healthy athletes

Side effects and risks

Typical supplement doses

The sleep studies used 3 g and were too small and too short to describe side effects reliably. Longer trials at much higher doses give some guide:

  • High doses were generally tolerated in psychiatric trials. Heresco-Levy’s group gave 0.8 g/kg/day for 6 weeks and described it as well tolerated (Heresco-Levy et al., Biol Psychiatry 2004).
  • Taste and nausea limit very large doses. In the OCD trial at up to 60 g/day, many participants stopped, mainly because of the taste or nausea (Greenberg et al., J Psychiatr Res 2009).
  • Large single doses may affect the brain. In healthy volunteers, a single oral dose of 0.8 g/kg (or 200 mg/kg intravenously) worsened sensorimotor gating (the brain’s filtering of incoming stimuli) and cognitive performance (Soh et al., GeroScience 2024).
  • GlyNAC was well tolerated in its trials. In the 24-week pilot, participants reported no gastrointestinal or other adverse effects, and creatinine and liver enzymes did not rise (Kumar et al., Clin Transl Med 2021). The Nestlé trial reported no serious adverse effects (Lizzo et al., Front Aging 2022).

Lessons from glycine absorbed in surgery

The 1.5% irrigation solution label describes what happens when large amounts of glycine enter the bloodstream. This applies to absorption during surgery, not to oral supplements, but it shows where glycine’s limits lie (Baxter label, DailyMed):

  • Large intravenous doses of glycine are known to cause salivation, nausea and lightheadedness.
  • In people with impaired liver function, ammonia produced from glycine breakdown may build up in the blood.
  • Large absorbed volumes can cause fluid overload and low blood sodium, which is why the label urges caution in severe heart, lung or kidney disease.

Who should be careful

There are no labeled warnings for oral glycine supplements. Based on the sources above, caution is reasonable in these groups:

  • People with severe liver or kidney disease. The irrigation label flags ammonia build-up in liver impairment and caution in kidney dysfunction.
  • People taking antipsychotic medicines. High-dose glycine has been tested as an add-on for schizophrenia, with inconsistent results. This should only happen under psychiatric care.
  • GlyNAC users. NAC has its own side effects and interactions, covered on the NAC page.

Key takeaways

  • A simple amino acid with many roles. Glycine makes up every third residue of collagen and is needed for glutathione, creatine and heme. It is also an inhibitory neurotransmitter and an NMDA receptor co-agonist.
  • The sleep evidence is thin. Three small crossover studies from one group, with 7–19 people analyzed for 2–4 nights each, found better subjective sleep and shorter time to fall asleep with 3 g at bedtime. A systematic review rated them at high risk of bias.
  • GlyNAC is early-stage. Open-label studies from one lab reported broad benefits in older adults. The only randomized trial from another group (117 adults, 2 weeks) found no rise in blood glutathione compared with placebo.
  • Most other uses are unproven. Single small trials in diabetes and metabolic syndrome showed modest marker changes. The largest schizophrenia trial was negative, and studies in athletes found no benefit.
  • Well tolerated in trials, with limits at very high doses. Doses up to 0.8 g/kg/day were tolerated in psychiatric trials, but taste and nausea caused many dropouts at 60 g/day. Large amounts absorbed into the blood may raise ammonia in people with liver disease.

Sources

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  28. 21 U.S.C. 321(ff). Definition of “dietary supplement.” govinfo.
  29. 21 CFR 170.50. Glycine (aminoacetic acid) in food for human consumption. eCFR.
  30. 21 CFR 172.812. Glycine. eCFR.
  31. World Anti-Doping Agency. The 2026 Prohibited List. WADA 2026 Prohibited List.