GlycineAmino Acid
3 g before bed
Adults — the dose used in every human sleep trial reviewed here
None set
Upper limit — No government or international agency has set a tolerable upper intake level for glycine. A 2023 review that derived first-ever ULs or NOAELs for 10 amino acids left glycine out, for want of dose-response toxicity trials [1].
A 2025 metabolic review reports oral doses up to 0.8 g/kg/day — roughly 56 g/day at 70 kg — used safely across clinical studies [2].
A 2024 review on physical performance flags a far lower caution point, above about 500 mg/kg (~35 g at 70 kg), on glutamate-toxicity grounds [4]. That figure rests mainly on animal and cell data, not on a human trial that tested the threshold.
For informational use only; not medical advice. Check with your doctor before starting, particularly if taking other meds.
Glycine is the smallest amino acid there is — its entire side chain is a single hydrogen atom [14].
The body makes most of its own, mainly from serine, which is why it was never classed as dietary-essential [2].
Several reviews now call it conditionally essential instead. Internal synthesis may fall behind demand in late pregnancy, on low-protein diets, and in insulin resistance or metabolic syndrome [2,9].
It is also structural. Glycine occupies every third position in collagen's triple helix, giving it roughly three times the share of any other single amino acid in collagen [16].
The name comes from the Greek glykys, sweet. It genuinely tastes sweet, close to glucose [7].
What the Evidence Actually Supports
- Sleep after a short nightPossibly helps
A randomized trial gave 3 g of glycine before bed after three nights of 25%-restricted sleep [5]. Next-day fatigue fell on a visual analog scale, and psychomotor vigilance test performance improved versus placebo.
Plasma melatonin and circadian clock-gene expression did not shift, so whatever is happening is not a melatonin effect [5].
A companion rat study found oral glycine shortened NREM sleep latency and lowered core body temperature via NMDA-receptor vasodilation [6]. That is animal data offering a plausible route, not a human result.
A 2024 systematic review across human organ systems found nervous-system outcomes to be glycine's most consistent human evidence, with metabolic and muscular ones thinner [20]. [5] - Negative symptoms in schizophrenia, without clozapinePossibly helps
Heresco-Levy and colleagues, in Archives of General Psychiatry, added 0.8 g/kg/day of glycine to conventional or non-clozapine atypical antipsychotics [3].
Negative symptoms fell 30% ± 16% over 6 weeks versus placebo, in patients with enduring negative-symptom schizophrenia [3].
That is a single trial at that dose. Nothing in the sources reviewed here replicates it. [3] - Added on top of clozapineNot shown to help
Here the direction flips. In patients maintained on clozapine at 400–1,200 mg/day, adding 30 g/day of glycine for 12 weeks moved neither positive nor negative symptoms [8].
The clozapine-only arm reached a 35% reduction in positive symptoms that the glycine arm never matched. The authors concluded glycine may interfere with clozapine's antipsychotic efficacy [8].
This rests on one small trial of 19 to 24 patients and needs replication. It is still the most consequential finding on this page for anyone taking clozapine. [8] - Lean mass in dialysis patientsPossibly helps
A randomized double-blind crossover trial in malnourished chronic hemodialysis patients gave 14 g/day of oral glycine for 4 months [11].
Fat-free mass index and handgrip strength both rose. An equal dose of branched-chain amino acids lowered fat-free mass index in the same patients [11].
Six of 27 people on glycine reported nausea or vomiting [11]. None of this extends to healthy adults or to athletes. [11] - Blood sugar and metabolic markersPossibly helps
A 2025 randomized clinical trial in adults with severe obesity found no significant change in HbA1c, fasting glucose, fasting insulin, HOMA-IR or the Matsuda index after two weeks [15].
The same trial did lower plasma triglycerides and the liver enzymes ALT and AST [15].
The sources disagree on what to make of that.
A metabolic review notes that low circulating glycine tracks with obesity, type 2 diabetes and fatty liver disease, and reads supplementation as a plausible lever [9]. The two-week trial did not deliver on the glycemic half of that. [15]
Forms, If You're Comparing Supplements
Free-form glycine powderReaching the multi-gram amounts the trials actually used, from 3 g upward .
Elemental contentPure free amino acid, with nothing chelated to it
AbsorptionHighly water-soluble — a manufacturer data sheet lists about 25 g per 100 mL of water at 25°C [21].
No study compared powder against capsules for absorption or effect. That is a genuine evidence gap, not a settled point [17].Best forReaching the multi-gram amounts the trials actually used, from 3 g upward [5].
Magnesium glycinateDelivering magnesium in a well-tolerated form, not for reaching a studied glycine dose .
Elemental contentMagnesium chelated to glycine — a magnesium product first, a glycine one second
AbsorptionPer WebMD, it raises levels of both magnesium and glycine [17].
The glycine delivered per dose is far smaller than a dedicated glycine serving. Magnesium-glycinate marketing is not glycine evidence.Best forDelivering magnesium in a well-tolerated form, not for reaching a studied glycine dose [17].
Collagen and gelatinPeople already taking collagen.
Elemental contentPeptide-bound glycine — 26–34% of gelatin's amino acid content by weight, per a USDA AMS technical review [13]
AbsorptionBound into peptides rather than free, so the kinetics differ from a glycine powder.
No head-to-head human comparison of the two turned up in this research [16].Best forPeople already taking collagen. A 2025 study tested a 3:1:1 glycine-proline-hydroxyproline blend with no placebo arm, so it says nothing about glycine alone [16].
Side Effects
- Nausea, vomiting, loose stools
The most consistently reported effect at higher doses. Six of 27 hemodialysis patients on 14 g/day reported nausea or vomiting over 4 months [11].
Similar gastrointestinal complaints appear across the 15–60 g/day schizophrenia literature [3]. The 3 g sleep dose sits an order of magnitude below that range. [11]
Precautions
- Liver disease and urea cycle disorders
Unlike most amino acids, glycine is broken down straight to ammonia rather than being transaminated first [2].
A 2025 metabolic review therefore flags a theoretical hyperammonemia risk at high intakes in people with liver disease or a urea cycle disorder [2]. It is a mechanistic caution, not a documented case series. [2] - Blood pressure — a disputed signal
INTERMAP, a cross-sectional study of 4,680 adults across the US, UK, Japan and China, linked higher dietary glycine to higher blood pressure [10].
A 2-SD-higher intake (+0.71 g/24h) tracked with 2.0–3.0 mmHg higher systolic pressure. The association ran stronger in Western participants, whose glycine came mainly from meat [10].
This is a dietary correlation, not a supplement trial. No study has tested glycine supplements against antihypertensive drugs, so that interaction question is open rather than answered either way [10]. [10] - Pregnancy and breastfeeding
Two different questions with two different answers. A stable-isotope trial found a real dietary glycine requirement in late gestation, weeks 31–40 [12].
On supplement safety, WebMD states plainly that the effect on pregnancy or a fetus is not known, and that whether glycine passes into breast milk is not known [17].
Higher physiological need in late pregnancy is documented. Supplement safety in that window is not. [12] - A laboratory nitrosation finding
The same 2025 review notes that gut bacteria can nitrosate glycine derivatives, which then react with DNA to form carboxymethylguanosine [2].
It is raised inside gastrointestinal-cancer research as a laboratory observation. Nothing in the sources connects it to a clinical outcome in supplement users [2]. [2]
Interactions
- Clozapine
The most consequential interaction on this page. In patients on clozapine at 400–1,200 mg/day, 30 g/day of glycine for 12 weeks produced no symptom improvement [8].
The placebo arm — clozapine alone — reached a 35% reduction in positive symptoms; the glycine arm did not. The trial authors concluded glycine may interfere with clozapine's antipsychotic efficacy [8].
Glycine added to non-clozapine antipsychotics did the opposite, improving negative symptoms [3]. The drug it is paired with changes the direction of the result, so this is not a class-wide statement about antipsychotics. [8]
Food Sources
Collagen-rich animal tissue is the concentrated source. A USDA Agricultural Marketing Service technical review of gelatin puts glycine at 26–34% of its amino acid content by weight, alongside proline at 10–18% [13].
Ordinary high-protein foods — meat, fish, dairy, legumes — are described as good sources, with a typical diet supplying around 2 g/day [7]. Population datasets land a little higher, at 2.7–4.7 g/day depending on the cohort [1].
What counts as a glycine-rich food is partly cultural. In INTERMAP, meat dominated for US and UK participants, grains and rice for Chinese participants, fish and rice for Japanese ones [10].
Best Time to Take
Before bed, if the goal is sleep. Every human trial that found a sleep benefit dosed 3 g at bedtime rather than at any other point in the day [5,6].
No source pinned down a precise window. The familiar "30 to 60 minutes before bed" figure was not traceable to a primary source here, so it is not stated as fact.
For every other goal, timing is untested. The dialysis trial split 14 g into two doses with no stated rationale, and the schizophrenia trials reported daily totals only [11].
Common Questions
Can I take glycine every night, long term?
Untested. The trial behind the 3 g bedtime dose ran around a three-night sleep-restriction protocol, not months of nightly use [5].
No multi-month or multi-year randomized trial of nightly glycine turned up in this research. Nothing in the sources points to a specific long-term risk either — the data simply stops.
Does glycine cause weight gain or water retention?
The only relevant trial ran in hemodialysis patients, where 14 g/day for 4 months raised fat-free mass rather than fat mass [11].
It caused no more fluid overload or pulmonary edema episodes than an equal dose of branched-chain amino acids [11].
That is a dialysis population. No trial has measured weight or fluid changes from glycine in healthy adults.
Can high-dose glycine cause kidney stones?
The human data is thin and points both ways. In 6 stone-formers and 6 healthy men given about 4 g/day for a week, urinary oxalate rose in some but not all, without reaching significance [19].
Urinary calcium and urine volume did rise significantly in the healthy men, yet the calculated probability of stone formation did not shift [19].
Separately, a rat study found glycine suppressed calcium-oxalate crystal formation, and human stone patients had lower urine glycine than controls [18]. Rat kidneys are not human kidneys, and no supplementation trial has tested the question properly.
Does glycine do anything for skin or collagen?
Glycine sits at every third position in collagen's triple helix, roughly three times the share of any other single amino acid [16].
A 2025 human study of a 3:1:1 glycine-proline-hydroxyproline blend reported better skin appearance and a lower biological-age marker over 6 months [16].
That study tested the blend, had no placebo arm, and never isolated glycine. It does not tell you what glycine alone does for skin.
Why does glycine taste sweet, and can it replace sugar?
The sweetness is real, and it is where the name comes from — Greek glykys, sweet, with a taste close to glucose [7].
One review notes this makes it a popular addition to health-focused drinks [7].
No source tested it as a sugar substitute. It is an amino acid carrying calories and nitrogen, unlike a non-nutritive sweetener [2].
Is glycine polar or nonpolar?
Nonpolar, by the standard textbook classification [14].
Its side chain is a single hydrogen atom, which behaves much like the nonpolar alkyl chains of alanine or valine, despite not being an alkyl group [14].
You will see it called borderline or ambivalent in wider discussions, since a bare hydrogen has essentially no polarizing character in either direction.
Sources
- Elango et al., Advances in Nutrition — pmc.ncbi.nlm.nih.gov. https://pmc.ncbi.nlm.nih.gov/articles/PMC10334138/ (2023-04-13)
- Glycine as a conditionally essential amino acid and its relationship to l-serine — sciencedirect.com. https://www.sciencedirect.com/science/article/pii/S0026049525001994 (2025-08-31)
- Heresco-Levy et al., Archives of General Psychiatry — jamanetwork.com. https://jamanetwork.com/journals/jamapsychiatry/fullarticle/204616 (1998-12-31)
- Ramos-Jiménez et al., Sports — pmc.ncbi.nlm.nih.gov. https://pmc.ncbi.nlm.nih.gov/articles/PMC11510825/ (2024-09-24)
- Bannai et al., Frontiers in Neurology — pmc.ncbi.nlm.nih.gov. https://pmc.ncbi.nlm.nih.gov/articles/PMC3328957/ (2012-04-17)
- Kawai et al., Neuropsychopharmacology — pmc.ncbi.nlm.nih.gov. https://pmc.ncbi.nlm.nih.gov/articles/PMC4397399/ (2015-01-13)
- Razak et al., Oxidative Medicine and Cellular Longevity — pmc.ncbi.nlm.nih.gov. https://pmc.ncbi.nlm.nih.gov/articles/PMC5350494/ (2017-02-28)
- https://pubmed.ncbi.nlm.nih.gov/9892314 (date unknown)
- Alves et al., Nutrients — pmc.ncbi.nlm.nih.gov. https://pmc.ncbi.nlm.nih.gov/articles/PMC6627940/ (2019-06-15)
- https://pmc.ncbi.nlm.nih.gov/articles/PMC3683815/ (date unknown)
- Genton et al., Journal of Cachexia, Sarcopenia and Muscle — pmc.ncbi.nlm.nih.gov. https://pmc.ncbi.nlm.nih.gov/articles/PMC8718019 (2021-09-13)
- Rasmussen et al., The Journal of Nutrition — pmc.ncbi.nlm.nih.gov. https://pmc.ncbi.nlm.nih.gov/articles/PMC7850138/ (2020-09-15)
- https://www.ams.usda.gov/sites/default/files/media/Gelatin%20Fish%20TR%20Review.pdf (date unknown)
- Amino Acids - Glycine — biology.arizona.edu. https://biology.arizona.edu/biochemistry/problem_sets/aa/Glycine.html (date unknown)
- Tan et al., Scientific Reports — pmc.ncbi.nlm.nih.gov. https://pmc.ncbi.nlm.nih.gov/articles/PMC12534614/ (2025-10-16)
- A collagen amino acid composition supplementation reduces biological age in humans and increases health and lifespan in vivo | npj Aging — nature.com. https://www.nature.com/articles/s41514-025-00280-7 (2025-11-19)
- Glycine: Overview, Uses, Side Effects, Precautions, Interactions, Dosing and Reviews — webmd.com. https://www.webmd.com/vitamins-supplements/glycine (date unknown)
- https://pubmed.ncbi.nlm.nih.gov/33772775 (date unknown)
- Effect of glycine on urinary risk factors of kidney stone disease — sciencedirect.com. https://www.sciencedirect.com/science/article/pii/S0271531789800636 (2006-05-25)
- Janjira et al., GeroScience — link.springer.com. https://link.springer.com/article/10.1007/s11357-023-00970-8 (2024-01-31)
- https://www.sigmaaldrich.com/deepweb/assets/sigmaaldrich/product/documents/294/989/g7126pis.pdf (date unknown)