Glycine

Glycine (symbol Gly or G) is the smallest of the amino acids found in proteins and the only one that is achiral, since its side chain is a single hydrogen atom that makes the molecule superimposable on its mirror image. It is a white, sweet-tasting crystalline solid, a property reflected in its name, which derives from the Greek word for sweet. The compound was first isolated in 1820 by the French chemist Henri Braconnot, who obtained it by breaking down gelatin, and it was among the earliest amino acids to be characterized.

Glycine plays several distinct roles in the body. As a protein constituent it is especially prominent in collagen, where it makes up roughly a third of the residues and allows the tight coiling of the collagen triple helix. In the nervous system it functions as an inhibitory neurotransmitter, opening chloride channels at glycine receptors in the spinal cord, brainstem, and retina; the blocking of glycine release by tetanus toxin illustrates its importance in motor control. Glycine is also a metabolic precursor, contributing to the synthesis of glutathione, the porphyrin ring of heme, the purine bases of DNA and RNA, and creatine ^[1]. It is produced in the body mainly from the amino acid serine.

Although humans synthesize glycine, analyses of metabolic fluxes suggest that this internal production, together with a typical diet, may fall short of the amount needed for full collagen synthesis, supporting the view that glycine is semi-essential and that supplementation could be beneficial ^[2]. As a supplement it has been examined for sleep and for metabolic and muscle-related outcomes. Small studies report that glycine taken before bed can improve subjective sleep quality and reduce daytime fatigue and sleepiness after sleep restriction ^[3], and reviews of its use in exercise describe possible benefits for muscle protection and recovery while calling for more rigorous human trials ^[1][4].

Glycine is produced industrially in large quantities, chiefly by reacting chloroacetic acid with ammonia, and it is used as a flavoring and buffering agent, in the manufacture of other chemicals, and as a nutritional supplement. Dietary glycine comes largely from collagen-rich and protein-rich foods such as gelatin, meat, and legumes. It is widely available as an inexpensive powder; supplementation is generally well tolerated, though reviews note that very high intakes could raise concerns related to glycine's role in neurotransmission ^[4].

Tolerability. Trials describe 0.8 g/kg/day (about 56 g for a 70 kg adult) as well tolerated over 6 weeks (PMID 9892253, PMID 14732596). The practical limits at these doses are gastrointestinal and palatability related: nausea, loose stools, and the sheer sweet-tasting volume. In the stroke trial slight sedation occurred in 9 of 200 patients (4.5%) with no other marked adverse events (PMID 10629347). The 16-week GlyNAC randomized trial was reported as safe and well tolerated (PMID 35975308).

Interaction that matters. Glycine added to clozapine did not improve symptoms, and one trial explicitly raised the possibility that glycine interferes with clozapine's antipsychotic efficacy, since the clozapine-plus-placebo group improved 35% on positive symptoms while the glycine group did not (PMID 9892314). The larger 60 g/day trial found no benefit with clozapine either (PMID 10784481), and the 2021 meta-analysis found NMDA-modulator augmentation effective only with non-clozapine antipsychotics (PMID 33406959). Anyone on clozapine should treat high-dose glycine as a live interaction question.

Pushing the site in an intact brain is not automatically good. A single 0.8 g/kg dose in healthy men reduced mismatch negativity amplitude, an NMDA-dependent EEG measure (PMID 17952411).

The clearest large-load toxicity is surgical, not nutritional. When litres of 1.5% glycine irrigation are absorbed intravascularly during transurethral prostate resection, the result is TURP syndrome: dilutional hyponatraemia, hyperammonaemia, encephalopathy and transient visual disturbance or blindness (PMID 9252792, PMID 6492293). This is not what an oral supplement does, but it is the best-documented evidence of what a very large glycine load can do, and glycine is metabolised to ammonia by the glycine cleavage system. Caution in advanced liver disease or urea-cycle disorders follows from that mechanism rather than from any trial.

Non-ketotic hyperglycinaemia, or glycine encephalopathy, is the inherited failure of glycine breakdown and defines the ceiling of what accumulated brain glycine does (PMID 36415754). It is not caused by supplementation.

No tolerable upper intake level has been set for glycine by any authority.

Regulatory. United States: the FDA rescinded glycine's GRAS status for human food in 1971 under 21 CFR 170.50, on evidence of adverse effects at high levels in animal diets and rising dietary exposure; GRAS status for animal feed was left intact, and glycine remains permitted as a food additive under narrow provisions and is sold freely as a dietary supplement. European Union: authorised food additive E 640 (glycine and its sodium salt), with specifications in Commission Regulation (EU) No 231/2012. As a medicine glycine carries ATC code B05CX03 and 1.5% glycine irrigation is a licensed sterile product. Glycine is not a controlled substance in any jurisdiction found.

WADA: glycine is not named on the Prohibited List and no prohibited class covers a dietary amino acid, so it is treated as permitted. The 2026 list PDF could not be fetched to quote directly, so this is reported as not listed rather than as a verified quotation.

Glycine acts as a co-agonist at the N-methyl-D-aspartate (NMDA) receptor and is used as an augmentation agent to antipsychotic medications for treatment of schizophrenia, particularly negative symptoms.

Meta-analysis of 40 randomized controlled trials involving 4,937 patients demonstrated that glycine, along with D-serine and sarcosine, improved multiple schizophrenia symptom domains when added to antipsychotics other than clozapine, with a favorable safety profile and minimal adverse events. ^[31] The augmentation strategy works through indirect enhancement of glutamatergic transmission; however, glycine shows no benefit in clozapine-resistant patients, and its efficacy is limited in patients already receiving clozapine monotherapy. ^[32] Clinical trials suggest glycine at typical doses of 0.8 g/kg weekly show no significant benefit over placebo in reducing alcohol consumption or craving in patients with comorbid schizophrenia and alcohol dependence, indicating that benefit in schizophrenia does not necessarily translate to other psychiatric or substance use disorders. ^[33]

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Glycine was among the first amino acids ever isolated, obtained in 1820 by the French chemist Henri Braconnot, who boiled gelatin with sulfuric acid and recovered a sweet-tasting crystalline substance he called the 'sugar of gelatin.' Because of its mildly sweet taste the compound was later given the name glycine, from the Greek 'glykys' for sweet, and was for a time also called glycocoll. Its structure was clarified in 1858 by Auguste Cahours, who recognized it as an amino derivative of acetic acid, making it the simplest of the proteinogenic amino acids. Long understood as a fundamental building block of proteins and an inhibitory neurotransmitter, glycine later found use as a dietary supplement studied for sleep and cognitive support.