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The AtlasAmino acidsNonpolar, aliphatic

GlycineGly · G

The smallest amino acid, with a single hydrogen for a side chain: every third residue of collagen, the first atoms of heme, and an inhibitory transmitter in the spinal cord.

Status Reference · not yet an episodeSources 40Reviewed October 2026
Structural formula of Glycine, C2H5NO2.
Skeletal formula — every corner and every line end is a carbon, and the hydrogens on carbon are left implied.

Molecule · Gly · 5 heavy atoms

Glycine

C2H5NO275.07 g/mol

The smallest amino acid, with a single hydrogen for a side chain: every third residue of collagen, the first atoms of heme, and an inhibitory transmitter in the spinal cord.

Built fromthe charted ones open their own entry

Codes
Gly · G
Formula
C2H5NO2
Molar mass
75.07 g/mol
Systematic name
2-aminoacetic acid
Side chain
A single hydrogen atom; the smallest and most flexible residue in proteins.
Class
Nonpolar, aliphatic
In the diet
Conditionally essential
Carbon skeleton
Glucogenic
pKa
α-COOH 2.34 · α-NH3+ 9.60
Isoelectric point
pH 5.97
Hydropathy
-0.4 (Kyte–Doolittle)
Codons
GGU GGC GGA GGG
Main transporters
SLC6A9 (GlyT1), SLC6A5 (GlyT2)

pKa and isoelectric point: Nelson and Cox, Lehninger Principles of Biochemistry, table of amino acid properties (free amino acid, 25 °C). Hydropathy: Kyte and Doolittle, J Mol Biol 1982. Essentiality: Reeds, J Nutr 2000. Formula and mass computed from the structure.

In brief

What it is

The simplest amino acid: its side chain is one hydrogen atom, so it is the only one without left- and right-handed forms. The body makes it, mostly from serine 1.

Why it matters

Collagen, the most abundant protein in animals, is built on glycine at every third position 2; heme begins with glycine 3; and glycine is an inhibitory transmitter in the spinal cord and brainstem and a co-agonist of the NMDA receptor in the brain 4,5.

Where it runs short

Glycine is made, but perhaps not in enough: one estimate puts synthesis at about 3 g a day and diet at 1.5 to 3 g, against needs that may be about 10 g a day higher, mostly for collagen 1.

Where it turns

When the glycine cleavage system fails, glycine accumulates in every tissue, especially the brain, and severe nonketotic hyperglycinemia causes intractable seizures and no developmental progress 6,7.

A molecule with nothing on its side chain turns out to be a structural, signaling and metabolic requirement all at once.

The molecule

Glycine’s side chain is a hydrogen atom. That makes it the smallest residue, and the most flexible: it can take backbone angles no other amino acid can, which is why it turns up in tight turns and at the center of collagen’s triple helix 2.

Collagen is a right-handed bundle of three left-handed helices 2. Every third position faces the crowded axis where the three chains meet, and only glycine fits there. In osteogenesis imperfecta, substituting another amino acid for one of these glycines in type I collagen weakens bone, and in some stretches of the chain, where collagen binds its partners, the substitution is lethal 8,9.

StereochemistryGlycine has no stereocentre: with hydrogen as its side chain, its α-carbon carries two identical groups, so there is no L- or D-glycine.

Charge · pHGlycine carries almost no net charge at the pH of blood.
+2+10-1-202468101214Blood · pH 7.4pI 5.97pHNet charge

Move across the chart to read the charge at any pH.

Computed from its pKa values (α-carboxyl 2.34, α-amino 9.60) by the Henderson–Hasselbalch equation, for the free amino acid in water at 25 °C. Inside a folded protein the same groups can shift by a unit or more. The faint lines are the other amino acids.

HydropathyGlycine scores -0.4: the 13th most water-loving of the twenty.
-4-20+2+4Arginine, -4.5RLysine, -3.9KAspartate, -3.5DGlutamate, -3.5EAsparagine, -3.5NGlutamine, -3.5QHistidine, -3.2HProline, -1.6PTyrosine, -1.3YTryptophan, -0.9WSerine, -0.8SThreonine, -0.7TGlycine, -0.4GAlanine, +1.8AMethionine, +1.9MCysteine, +2.5CPhenylalanine, +2.8FLeucine, +3.8LValine, +4.2VIsoleucine, +4.5I← Water-lovingWater-avoiding →

Kyte–Doolittle hydropathy index: positive values avoid water and tend to be buried inside a folded protein, negative values sit on its surface. Each letter is an amino acid; choose one to open it.

The genetic codeGlycine has 4 codons. The code is redundant, so most single-letter changes at the third position still write glycine.
The 64 codons of the standard genetic code. Codons for glycine are marked.
1st ↓  2nd →UCAG3rd
UUUUPheUCUSerUAUTyrUGUCysU
UUCPheUCCSerUACTyrUGCCysC
UUALeuUCASerUAAStopUGAStopA
UUGLeuUCGSerUAGStopUGGTrpG
CCUULeuCCUProCAUHisCGUArgU
CUCLeuCCCProCACHisCGCArgC
CUALeuCCAProCAAGlnCGAArgA
CUGLeuCCGProCAGGlnCGGArgG
AAUUIleACUThrAAUAsnAGUSerU
AUCIleACCThrAACAsnAGCSerC
AUAIleACAThrAAALysAGAArgA
AUGMetACGThrAAGLysAGGArgG
GGUUValGCUAlaGAUAspGGUGlyU
GUCValGCCAlaGACAspGGCGlyC
GUAValGCAAlaGAAGluGGAGlyA
GUGValGCGAlaGAGGluGGGGlyG

Where it comes from

The body makes glycine mainly from serine, by serine hydroxymethyltransferase, which also produces a one-carbon unit for folate metabolism. Comparing every reported flux in an adult, synthesis from serine provided more than 85% of glycine, about 3 g a day 1.

The same analysis estimated that synthesis plus 1.5 to 3 g from the diet may fall around 10 g a day short of total use, mostly by collagen, and argued that glycine should count as semi-essential 1. This is a calculation, not a measured deficiency.

Conditionally essentialMade mainly from serine, more than 85% of the total, by serine hydroxymethyltransferase; because that reaction yields only as much glycine as one-carbon units, some authors argue glycine is semi-essential 1,10.

How much

None set; the body makes it, though some argue not in sufficient amounts 1.

Where it is in food

  • Gelatin and collagen are about one-third glycine; collagen supplements raise blood glycine 2,11.

In the bottle · syntheticCommercial glycine is mostly made by chemical synthesis; because it has no stereocentre, there is no natural or unnatural form to choose between 12.

What the body does with it

Glycine is a building block for more molecules than its size suggests. The whole glycine molecule goes into creatine, along with parts of arginine and methionine 13. It is the third amino acid of glutathione 14. It supplies the carbons and nitrogen that begin heme 3. And through glycine-acyltransferase it conjugates carboxylic acids such as benzoate, so that they can be excreted 15,16.

In the spinal cord and brainstem glycine is an inhibitory transmitter. Its receptors are chloride channels built from α1 and β subunits, and a presynaptic transporter, GlyT2, recaptures it for reuse; mutations in all three cause hyperekplexia, startle disease 4,17,18.

In the brain glycine also works the other way. In 1987 it was found to potentiate the excitatory NMDA receptor through a site insensitive to strychnine 5; extrasynaptic NMDA receptors use glycine as their co-agonist, while synaptic ones prefer D-serine 19.

That second role — glycine as the co-agonist the NMDA receptor cannot open without — has carried the most ambitious drug program built on any amino acid, and in 2025 it ended. Iclepertin blocks the glycine transporter GlyT1, raising synaptic glycine, on the theory that this would lift the cognitive impairment of schizophrenia, for which there is no treatment at all. CONNEX-1, -2 and -3 randomized 1,835 adults across 338 psychiatric centers in 41 countries to 10 mg daily or placebo for 26 weeks on top of their antipsychotic. The adjusted mean difference on the MATRICS cognitive composite was 0.127 points (95% CI −0.396 to 0.650; p = 0.63) 20. It was well tolerated and it did nothing, in the largest test the hypothesis has had.

In three sentences each

Every third residue of collagen

Collagen is three helices wound into a rope, and only glycine is small enough to sit at the center where they touch, so the sequence repeats Gly-X-Y; substituting another amino acid for one glycine is a classic cause of osteogenesis imperfecta 2,9.

Two opposite signals

Glycine opens chloride-channel receptors that inhibit neurons in the spinal cord and brainstem, and separately is a co-agonist the excitatory NMDA receptor needs alongside glutamate 4,5,19.

The first atoms of heme

Aminolevulinic acid synthase joins glycine to succinyl-CoA to make aminolevulinic acid, the first step of heme synthesis; red cells import glycine for it through the transporter GlyT1 3,21.

How it is made, moved and broken down

Glycine is broken down by the mitochondrial glycine cleavage system into CO₂, ammonia and a one-carbon unit carried by folate. When it fails, glycine accumulates; molecular analysis in 124 patients identified 99% of mutant alleles, mostly in the gene for its P-protein 7.

Carbon skeleton · glucogenicConverted to serine and on to pyruvate, or split by the glycine cleavage system into CO₂, ammonia and a one-carbon unit 1,7.

Made from serineMore than 85% of the body’s glycine 1.
  1. Serine + THF
  2. Serine hydroxymethyltransferaseSHMT1, SHMT2 · vitamin B6
  3. Glycine + 5,10-methylene-THF
Broken downIts failure causes nonketotic hyperglycinemia 6,7.
  1. Glycine + THF
  2. Glycine cleavage systemGLDC, AMT, GCSH · vitamin B6, lipoate, NAD⁺
  3. CO₂ + NH₃ + 5,10-methylene-THF
Into heme and creatineTwo large consumers 3,13.
  1. Glycine + succinyl-CoA
  2. ALA synthaseALAS1, ALAS2 · vitamin B6
  3. δ-Aminolevulinic acid
  4. AGAT, then GAMTGATM, GAMT · SAM
  5. Guanidinoacetate → creatine

How it crosses membranes

  • SLC6A9 · GlyT1red cell precursors, astrocytes — imports glycine for heme; its inhibitor bitopertin lowers protoporphyrin 21,22
  • SLC6A5 · GlyT2presynaptic glycinergic neurons — recaptures glycine for release; mutations cause startle disease 17

Where it matters most

Connective tissue and bone
Collagen is glycine at every third residue 2,9.
Spinal cord and brainstem
Inhibitory glycinergic synapses 4.
Bone marrow
Red cell precursors import glycine through GlyT1 for heme 21.
Liver and kidney
Glycine conjugation of benzoate and other acids for excretion 15.
Muscle
Creatine synthesis consumes whole glycine molecules 13.

When it goes wrong

Inherited

Nonketotic hyperglycinemia

GLDC, AMT · autosomal recessive

Glycine accumulates in all tissues, especially the brain. The severe form brings intractable epilepsy and no developmental progress; the attenuated form is variable 6. In 124 patients, brain malformations were common in the severe form, 71%, and rare in the attenuated, 7.5% 7. Treatment with sodium benzoate, to conjugate glycine, and NMDA receptor blockers such as dextromethorphan is not curative 6. A 2026 comparison in 14 children makes the dietary position plainer: neither a ketogenic diet (n = 8) nor a glycine-restricted diet (n = 6) changed plasma glycine, motor function or swallowing, and mortality was high in both — but seizure frequency, seizure scores and antiepileptic drug use fell on the ketogenic diet, and seizure frequency ROSE on the restricted one 23. Restricting the amino acid whose accumulation names the disease is the obvious move, and on this evidence it is not the better one.

How it is foundPaired CSF and plasma glycine; GLDC and AMT sequencing 7.

Inherited

Hyperekplexia (startle disease)

GLRA1, GLRB, SLC6A5 · dominant or recessive

Newborn stiffness, exaggerated startle and stiffening after the startle, with a risk of apnoea and sudden death; most motor features respond to clonazepam 4,24. GLRA1 and SLC6A5 are the main genes, with GLRB the third 17,18.

How it is foundClinical, including the nose-tap test, and gene panel 24.

Inherited

Osteogenesis imperfecta

COL1A1, COL1A2 and others · mostly dominant

Fragile, deformed bones from defects of type I collagen or the proteins that process it 9. Glycine substitutions in the collagen helix are a major cause, and in some regions are lethal 8.

How it is foundClinical and genetic testing 9.

Drug

Erythropoietic protoporphyria

FECH, ALAS2

Protoporphyrin builds up in red cells and causes painful reactions to sunlight 3. In a phase 2 trial in 75 adults, the GlyT1 inhibitor bitopertin lowered protoporphyrin by 30 to 50% against placebo and reduced phototoxic reactions 22.

How it is foundWhole-blood metal-free protoporphyrin 22.

How it is measured

Glycine is part of the standard plasma, urine and CSF amino acid analysis, by ion-exchange chromatography or mass spectrometry 25. For nonketotic hyperglycinemia, paired CSF and plasma samples give both the diagnosis and a guide to prognosis 7.

Where plasma glycine is genuinely informative is as a marker rather than a target, and two 2026 analyses show both halves of that. In 2,408 people — 1,456 with MRI-confirmed lacunar stroke — 211 of 250 measured metabolites were associated with the disease, and Mendelian randomization supported a causal association for exactly two of them; glycine was one, inversely associated with isolated lacunar infarcts (OR 0.704, 95% CI 0.585 to 0.848) 26. In UK Biobank, higher plasma glycine went with a lower biological-age residual (β −0.729, 95% CI −0.815 to −0.643), partly mediated by inflammatory and redox markers 27. An association with a composite index is not a reason to take a supplement, and the second paper's own interaction analysis — the effect weakened in men eating a pro-inflammatory diet — says as much.

  • CSF and plasma glycineMeasured together to diagnose nonketotic hyperglycinemia, as part of the standard amino acid analysis 7,25.In 124 patients, CSF glycine above 230 µmol/L indicated a severe outcome and a CSF-to-plasma ratio of 0.08 or less predicted the attenuated form 7.Paired samples must be taken at the same time, and valproate raises glycine, which can unmask or mimic the disease 28.

Food, supplements and the evidence

Establishedreplicated in people, for a named outcome

  • Sodium benzoate, which removes glycine as hippurate, is part of treatment for nonketotic hyperglycinemia 6.

Uncertainsmall, short, mixed, surrogate or preclinical

  • Glycine, 3 g at bedtime, for sleep quality and next-day fatigue: three small trials, all positive, all from closely related groups 11,29.
  • GlyNAC, glycine with N-acetylcysteine, in aging: one small trial in 24 older adults reported broad improvements 14, while a 114-person trial in healthy older adults found no rise in glutathione, its primary endpoint 30.
  • Glycine and lifespan: 4 to 6% longer life in mice 31; no human data.
  • Glycine for the muscle lost in critical illness. 29 mechanically ventilated patients were randomized to enteral glycine at 0.2 or 0.4 g/kg/day or placebo for up to seven days, with ultrasound and needle biopsies of the vastus lateralis. Plasma and muscle glycine both rose dose-dependently — the delivery worked. Quadriceps thickness loss was numerically smaller on the high dose (mean difference 0.11 cm, 95% CI −0.10 to 0.31, p = 0.299) and myofibre diameter did not change at all 32. The trial was designed to show the amino acid gets there, and it did; whether that matters is the next trial's question.
  • Glycine in severe obesity, where the deficiency is real and the mechanism it was supposed to fix did not move. 19 people with a BMI of 38.3 took 100 mg/kg a day for two weeks: plasma glycine rose, urinary acylglycines rose — the conjugation pathway that clears excess metabolites sped up — triglycerides and aminotransferases fell, and the glutamate–serine–glycine index improved. Glutathione did not change, which is the pathway glycine is usually sold for, and neither did body weight 33.

Sold asthe claim on the label, against the evidence

  • “GlyNAC reverses aging.” The positive human evidence comes from one research group’s small trials; an independent, larger trial missed its primary endpoint 14,30.
  • “Glycine for alcohol craving.” Rat work showed glycine acting at glycine receptors in reward regions and reducing alcohol intake. In people with alcohol use disorder given 0.12 g/kg for five days, serum glycine rose 125% — and neither craving, nor the subjective effects of alcohol, nor how much they drank in a laboratory self-administration session differed from placebo 34. The dose reached the blood and the behavior did not follow.
  • “Collagen peptides turn back your biological age.” A 2025 paper identified the active unit of ingested collagen as a 3:1:1 ratio of glycine to proline to hydroxyproline, extended lifespan in C. elegans, improved grip strength in 20-month-old mice, and reported a 1.4-year reduction in biological age at six months in people (p = 0.04) 35. The human arm is an observational trial, not randomized against placebo; the biological-age clock is a commercial one; and several authors are employed by the company selling the composition. The worm and mouse data are the strong part, and they are not about people.
  • And one thing glycine is sold for that the causal evidence runs against: bone. In 18,769 UK Biobank participants, circulating glycine was negatively associated with bone mineral density (β −0.0486, p = 0.004), and Mendelian randomization supported a causal negative association in women (β −0.022, 95% CI −0.037 to −0.007) 36. Collagen is a third glycine by residue, which is exactly why that result is worth printing rather than leaving out.

What is strange about it

A drug that blocks a glycine transporter may treat a disease of sunlight. Erythropoietic protoporphyria has one approved treatment, which does not touch its cause 37; bitopertin, by starving red cell precursors of glycine for heme, cut protoporphyrin by up to half and reduced reactions to sunlight in a 17-week trial 21,22.

In the Interventions Testing Program, which tests drugs and diets in genetically mixed mice, a diet with 8% glycine extended median lifespan by 4 to 6% in both sexes 31. In people, genetic analysis of 80,003 participants supports a protective link between glycine and coronary disease, but suggests the link with diabetes runs the other way, insulin resistance lowering glycine 38.

Glycine for sleep rests on three small trials, a rat study that traced the effect to NMDA receptors in the body-clock region of the brain and a fall in core temperature, and a 2026 scoping review that called the mechanism plausible 11,29,39.

Glycine is also what makes the gentlest iron tablet gentle: ferrous bis-glycinate is iron chelated to two glycines, sold on the claim of better absorption and fewer gut symptoms. One of the randomized trials behind that claim, comparing it with ferrous glycine sulfate in iron deficiency anemia of pregnancy, was retracted by its journal in 2026 40. The chemistry of chelation is not in doubt. One of the clinical comparisons is now formally withdrawn, and a page that cited it without saying so would be repeating a paper that no longer exists.

Where it connects

On the map

A star in Longevity & NAD, one of 14. Made in the body but not always in enough: shortfalls show up in glutathione, collagen — and in homocysteine.

Find it on the map

Sources

40 sources, numbered as they are cited. Every one was checked against PubMed or its publisher before it was cited here; the note under each says what it shows and what it does not.

  1. 1
    Meléndez-Hevia E, De Paz-Lugo P, Cornish-Bowden A, et al. A weak link in metabolism: the metabolic capacity for glycine biosynthesis does not satisfy the need for collagen synthesis.J Biosci · 2009 · 34(6):853–872doi:10.1007/s12038-009-0100-9 · PMID 20093739

    A flux calculation, not a measured deficiency.

  2. 2
    Shoulders MD, Raines RT. Collagen structure and stability.Annu Rev Biochem · 2009 · 78:929–958doi:10.1146/annurev.biochem.77.032207.120833 · PMID 19344236

    The triple helix.

  3. 3
    Di Pierro E, Granata F, De Canio M, et al. Recognized and emerging features of erythropoietic and X-linked protoporphyria.Diagnostics (Basel) · 2022 · 12(1):151doi:10.3390/diagnostics12010151 · PMID 35054318

    ALAS2 joins glycine and succinyl-CoA.

  4. 4
    Bode A, Lynch JW. The impact of human hyperekplexia mutations on glycine receptor structure and function.Mol Brain · 2014 · 7:2doi:10.1186/1756-6606-7-2 · PMID 24405574

    Glycine receptors and startle disease.

  5. 5
    Johnson JW, Ascher P. Glycine potentiates the NMDA response in cultured mouse brain neurons.Nature · 1987 · 325(6104):529–531doi:10.1038/325529a0 · PMID 2433595

    The discovery of the NMDA co-agonist site.

  6. 6
    Nowak M, Chuchra P, Paprocka J. Nonketotic hyperglycinemia: insight into current therapies.J Clin Med · 2022 · 11(11):3027doi:10.3390/jcm11113027 · PMID 35683414

    Benzoate and NMDA antagonists; no causal treatment.

  7. 7
    Swanson MA, Coughlin CR, Scharer GH, et al. Biochemical and molecular predictors for prognosis in nonketotic hyperglycinemia.Ann Neurol · 2015 · 78(4):606–618doi:10.1002/ana.24485 · PMID 26179960

    124 patients; CSF glycine and the ratio as predictors.

  8. 8
    Sałacińska K, Pinkier I, Rutkowska L, et al. Novel mutations within collagen alpha1(I) and alpha2(I) ligand-binding sites, broadening the spectrum of osteogenesis imperfecta: current insights into collagen type I lethal regions.Front Genet · 2021 · 12:692978doi:10.3389/fgene.2021.692978 · PMID 34306033

    Lethal regions of glycine substitution.

  9. 9
    Forlino A, Marini JC. Osteogenesis imperfecta.Lancet · 2016 · 387(10028):1657–1671doi:10.1016/S0140-6736(15)00728-X · PMID 26542481

    Seminar.

  10. 10
    Reeds PJ. Dispensable and indispensable amino acids for humans.J Nutr · 2000 · 130(7):1835S–1840Sdoi:10.1093/jn/130.7.1835S · PMID 10867060

    Glycine as conditionally indispensable.

  11. 11
    Fan Z, Nelson JM, Wallace TC. Glycine bioavailability and sleep-related outcomes following oral glycine and collagen supplementation: a scoping review.J Diet Suppl · 2026 · 23(5):602–622doi:10.1080/19390211.2026.2726197 · PMID 42687500

    22 trials; three on glycine and sleep.

  12. 12
    Leuchtenberger W, Huthmacher K, Drauz K. Biotechnological production of amino acids and derivatives: current status and prospects.Appl Microbiol Biotechnol · 2005 · 69(1):1–8doi:10.1007/s00253-005-0155-y · PMID 16195792

    Fermentation, enzymatic and chemical routes.

  13. 13
    Brosnan JT, da Silva RP, Brosnan ME. The metabolic burden of creatine synthesis.Amino Acids · 2011 · 40(5):1325–1331doi:10.1007/s00726-011-0853-y · PMID 21387089

    The whole glycine molecule goes into creatine.

  14. 14
    Kumar P, Liu C, Suliburk J, et al. 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):75–89doi:10.1093/gerona/glac135 · PMID 35975308

    24 older adults; one research group.

  15. 15
    Rohwer JM, Schutte C, van der Sluis R. Functional characterisation of three glycine N-acyltransferase variants and the effect on glycine conjugation to benzoyl-CoA.Int J Mol Sci · 2021 · 22(6):3129doi:10.3390/ijms22063129 · PMID 33803916

    The glycine conjugation pathway.

  16. 16
    Nourbakhsh M, Miryounesi M, Tale A, et al. Glycine-acyltransferase deficiency due to a homozygous nonsense variant in the GLYAT: a novel inborn error of metabolism.JIMD Rep · 2025 · 66(5):e70032doi:10.1002/jmd2.70032 · PMID 40747359

    First reported case.

  17. 17
    Carta E, Chung SK, James VM, et al. Mutations in the GlyT2 gene (SLC6A5) are a second major cause of startle disease.J Biol Chem · 2012 · 287(34):28975–28985doi:10.1074/jbc.M112.372094 · PMID 22700964

    SLC6A5 in 17 of 93 index cases.

  18. 18
    Chung SK, Bode A, Cushion TD, et al. GLRB is the third major gene of effect in hyperekplexia.Hum Mol Genet · 2013 · 22(5):927–940doi:10.1093/hmg/dds498 · PMID 23184146

    117 gene-negative cases screened.

  19. 19
    Papouin T, Ladépêche L, Ruel J, et al. Synaptic and extrasynaptic NMDA receptors are gated by different endogenous coagonists.Cell · 2012 · 150(3):633–646doi:10.1016/j.cell.2012.06.029 · PMID 22863013

    D-serine at synapses, glycine outside them. Rodent work.

  20. 20
    Keefe RSE, Harvey PD, Correll CU, et al. Efficacy and safety of iclepertin for cognitive impairment associated with schizophrenia (CONNEX programme): results from three phase 3 randomised controlled trials.Lancet Psychiatry · 2025 · 12(12):906–920doi:10.1016/S2215-0366(25)00296-2 · PMID 41233083

    Three trials, 338 centers, 41 countries, 1,835 patients. The glycine hypothesis of schizophrenia, tested at the largest scale it has ever been.

  21. 21
    Ducamp S, Wu M, Putra J, et al. The GLYT1 inhibitor bitopertin mitigates erythroid PPIX production and liver disease in erythroid protoporphyria.J Clin Invest · 2025 · 135(18)doi:10.1172/JCI181875 · PMID 40663422

    Preclinical; GlyT1 in erythroid cells.

  22. 22
    Yeung AK, Bonkovsky HL, Balwani M, et al. Bitopertin shows efficacy in patients with erythropoietic protoporphyria: results from the randomized, double-blind, placebo-controlled AURORA trial.J Am Acad Dermatol · 2025 · 94(4):1167–1176doi:10.1016/j.jaad.2025.12.024 · PMID 41390126

    75 adults, 17 weeks; small and short.

  23. 23
    Bozacı AE, Erdal İ, Öner G, et al. Clinical and laboratory outcomes of ketogenic versus glycine-restricted diet in nonketotic hyperglycinemia: a comparative study.Mol Genet Metab · 2026 · 148(2):110118doi:10.1016/j.ymgme.2026.110118 · PMID 41966573

    Fourteen children. Neither diet moved plasma glycine; one of them moved the seizures.

  24. 24
    Falsaperla R, Sortino V, Giacchi V, et al. Neonatal hyperekplexia: is it still a diagnostic challenge? Evidence from a systematic review.J Child Neurol · 2024 · 39(11–12):415–424doi:10.1177/08830738241273425 · PMID 39223854

    14 genetically confirmed newborns.

  25. 25
    Sharer JD, De Biase I, Matern D, et al. Laboratory analysis of amino acids, 2018 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG).Genet Med · 2018 · 20(12):1499–1507doi:10.1038/s41436-018-0328-6 · PMID 30459394

    Methods for amino acid analysis.

  26. 26
    Ng WH, Aghakishiyeva E, Markus HS, Harshfield EL. Metabolic markers of MRI-confirmed lacunar stroke: observational and Mendelian randomization analyses.Neurology · 2026 · 107(7):e218409doi:10.1212/WNL.0000000000218409 · PMID 42721413

    250 metabolites measured, 211 associated, and two that survived the causal test. Glycine is one of them.

  27. 27
    Xu H, Pan S, Qi H, et al. Plasma glycine decelerates biological aging via the redox-inflammatory axis: a large-scale study modulated by sex and dietary patterns.Free Radic Biol Med · 2026 · 252:286–294doi:10.1016/j.freeradbiomed.2026.04.163 · PMID 42105789

    UK Biobank. An association with a biological-age residual, which is a composite of things glycine might not be causing.

  28. 28
    Subramanian V, Kadiyala P, Hariharan P, et al. A rare case of glycine encephalopathy unveiled by valproate therapy.J Pediatr Neurosci · 2015 · 10(2):143–145doi:10.4103/1817-1745.159200 · PMID 26167219

    Case report.

  29. 29
    Bannai M, Kawai N, Ono K, et al. The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers.Front Neurol · 2012 · 3:61doi:10.3389/fneur.2012.00061 · PMID 22529837

    3 g at bedtime after three nights of restricted sleep.

  30. 30
    Lizzo G, Migliavacca E, Lamers D, et al. 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 · 3:852569doi:10.3389/fragi.2022.852569 · PMID 35821844

    114 people, two weeks; no rise in glutathione.

  31. 31
    Miller RA, Harrison DE, Astle CM, et al. Glycine supplementation extends lifespan of male and female mice.Aging Cell · 2019 · 18(3):e12953doi:10.1111/acel.12953 · PMID 30916479

    Interventions Testing Program; 4–6% longer median life.

  32. 32
    Ali Abdelhamid Y, Bongetti AJ, Caldow MK, et al. The effect of enteral glycine on plasma glycine and muscle structure, size, and function in the critically ill: a randomized controlled trial.Clin Nutr · 2025 · 54:233–242doi:10.1016/j.clnu.2025.10.001 · PMID 41109034

    29 patients, with needle biopsies. The amino acid reached the muscle; the muscle fibers did not change.

  33. 33
    Tan HC, Hsu JW, Tai ES, et al. Metabolic impact of dietary glycine supplementation in individuals with severe obesity.Sci Rep · 2025 · 15(1):36433doi:10.1038/s41598-025-20511-x · PMID 41107432

    19 people, two weeks. The deficiency corrected, the conjugation pathway sped up, and glutathione unmoved.

  34. 34
    Olsson Y, Lidö H, Ericson M, Söderpalm B. Evaluation of glycine treatment for reducing alcohol craving and self-administration in individuals with alcohol use disorder: a human laboratory trial.Alcohol Clin Exp Res (Hoboken) · 2025 · 49(12):2836–2854doi:10.1111/acer.70187 · PMID 41189445

    Serum glycine up 125%, and the drinking unchanged.

  35. 35
    Dakhovnik A, Mantovani M, Knufinke M, et al. A collagen amino acid composition supplementation reduces biological age in humans and increases health and lifespan in vivo.NPJ Aging · 2025 · 11(1):91doi:10.1038/s41514-025-00280-7 · PMID 41266379

    Worms, mice and an observational human arm, with authors from the company selling the composition.

  36. 36
    Chen S, Lu R, Zhang Y, et al. Associations of dietary and circulating choline and glycine with bone mineral density: UK Biobank analyses with Mendelian randomization.Int J Endocrinol · 2026 · 2026:2237464doi:10.1155/ije/2237464 · PMID 41971710

    18,769 people, and a causal estimate pointing the wrong way for a supplement sold for connective tissue.

  37. 37
    Barman-Aksözen J, Granata F, Wäscher S, et al. New and currently investigated pharmacotherapies for the erythropoietic protoporphyrias: spotlight on dersimelagon and bitopertin.Expert Opin Pharmacother · 2026 · 27(4):331–346doi:10.1080/14656566.2026.2651281 · PMID 41885813

    Afamelanotide the only approved treatment.

  38. 38
    Wittemans LBL, Lotta LA, Oliver-Williams C, et al. Assessing the causal association of glycine with risk of cardio-metabolic diseases.Nat Commun · 2019 · 10(1):1060doi:10.1038/s41467-019-08936-1 · PMID 30837465

    80,003 people; Mendelian randomization.

  39. 39
    Kawai N, Sakai N, Okuro M, et al. The sleep-promoting and hypothermic effects of glycine are mediated by NMDA receptors in the suprachiasmatic nucleus.Neuropsychopharmacology · 2015 · 40(6):1405–1416doi:10.1038/npp.2014.326 · PMID 25533534

    Rats.

  40. 40
    Retraction statement: 'Efficacy of ferrous bis-glycinate versus ferrous glycine sulfate in the treatment of iron deficiency anemia with pregnancy: a randomized double-blind clinical trial'.J Matern Fetal Neonatal Med · 2026 · 39(1):2649296doi:10.1080/14767058.2026.2649296 · PMID 41883305

    The trial behind the gentlest-iron claim, withdrawn by its journal.

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