Evidence Level
Moderate
7 Clinical Trials
6 Documented Benefits
3/5 Evidence Score

Glycine is a non-essential amino acid found in protein-rich foods and synthesized by the body, playing a key role in collagen formation, neurotransmitter function, and muscle repair. As a dietary supplement, it is often used to improve sleep quality, reduce inflammation, and support joint and skin health. Preliminary studies suggest glycine may enhance sleep, protect against muscle loss, and aid in metabolic health, but more research is needed to fully validate its benefits.

Studied Dose 3–5 g/day for sleep quality; metabolic/detox: 5–10 g/day; collagen support: 3–5 g/day alongside proline; generally recognized as safe at up to 1 g/kg body weight
Active Compound Glycine (free amino acid)

Benefits

Improved Sleep Quality

Glycine may enhance sleep by reducing core body temperature and calming the nervous system. Studies suggest 3 grams taken before bed can improve sleep onset and quality, reducing daytime fatigue.

Cognitive and Mood Support

Glycine acts as a neurotransmitter and may improve memory, attention, and mood. It’s involved in NMDA receptor function, which supports learning and memory. Some evidence links glycine to reduced symptoms of depression and anxiety.

Collagen and Joint Health

Glycine is a key component of collagen, supporting skin, joint, and connective tissue health. Supplementation may aid tissue repair and reduce joint pain, particularly in conditions like osteoarthritis.

Metabolic Health

Glycine may improve insulin sensitivity and reduce inflammation, potentially lowering the risk of metabolic disorders. It’s been studied for its role in managing blood sugar and protecting against oxidative stress.

Liver Protection

Glycine may support liver function by aiding detoxification and reducing damage from alcohol or toxins. It’s shown promise in animal studies for protecting against liver injury.

Muscle Preservation

Glycine may help prevent muscle wasting, especially in conditions like sarcopenia or during caloric restriction, by supporting protein synthesis.

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

Glycine lowers core body temperature by increasing cutaneous blood flow, facilitating sleep onset. It interacts with NMDA receptors in the suprachiasmatic nucleus (regulating circadian rhythms).

3

NMDA Receptor Modulation

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

4

GABAergic Effects

Its inhibitory action on glycine receptors reduces overexcitation, potentially alleviating anxiety and depression symptoms.

5

Collagen Synthesis

Glycine is a primary amino acid in collagen (about 33% of collagen’s structure), providing structural support for connective tissues, skin, and joints.

6

Anti-inflammatory Effects

Glycine inhibits pro-inflammatory cytokines (e.g., TNF-α, IL-6), reducing joint inflammation and supporting tissue repair.

7

Insulin Sensitivity

Glycine enhances insulin signaling, possibly by improving glutathione synthesis, which reduces oxidative stress and supports glucose uptake.

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

It reduces oxidative damage and inflammation in hepatocytes, protecting against alcohol- or toxin-induced liver injury.

11

Protein Synthesis

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

12

Anti-catabolic

It reduces muscle degradation by inhibiting inflammatory pathways and oxidative stress.

Clinical trials

1
GlyNAC (Glycine + N-Acetylcysteine) for Aging Hallmarks in Older Adults — Clinical Trial

Randomized, placebo-controlled trial in 24 older adults (mean age 65) and 12 young adults receiving GlyNAC (glycine 1.33 mmol/kg/day + NAC 0.81 mmol/kg/day) for 16 weeks. Outcomes: glutathione, oxidative stress, mitochondrial dysfunction markers, body composition, multi-system function. (Nutrients)

24 older adults + 12 young adult comparators. 16-week intervention.

GlyNAC improved or normalized: glutathione levels, oxidative stress markers, mitochondrial dysfunction, inflammation, insulin resistance, endothelial function, gait speed, cognition, body composition. Multiple aging hallmarks improved. Note: small sample, single research group (Sekhar lab at Baylor); independent replication needed. Promising but preliminary evidence for an emerging anti-aging intervention.

2
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.

3
GlyNAC Dose-Finding Clinical Trial in Older Adults

Randomized controlled trial in 114 healthy older adults (mean age 65) receiving GlyNAC at low (2.4 g/day), medium (4.8 g/day), or high (7.2 g/day) doses for 12 weeks. Outcomes: glutathione, biomarkers, tolerability. (2022)

114 healthy older adults. 12-week dose-finding.

Dose-dependent glutathione elevation; higher doses produced more robust biomarker improvements. Generally well-tolerated across doses. Adds dose-response data to the GlyNAC research program.

4
Oral Glycine for Cystic Fibrosis — Pilot Clinical Trial

Pilot clinical trial in children with cystic fibrosis receiving oral glycine vs placebo for 8 weeks. Outcomes: clinical status, spirometry (FEV1), inflammatory markers. (2017)

Children with CF (small pilot).

Modest improvements in inflammatory markers vs placebo; minimal effect on lung function. Pilot study; not established CF intervention. Modern CF management has been transformed by CFTR modulators (elexacaftor-tezacaftor-ivacaftor / Trikafta®) — supplemental glycine should not be considered comparable.

5
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 (0.4-0.8 g/kg/day, ~30-60 g for 75 kg adult) as adjuvant to antipsychotics. Outcomes: PANSS, negative symptoms. (Heresco-, Biol Psychiatry — or related work)

22 treatment-resistant schizophrenia patients. Crossover.

High-dose glycine reduced negative symptoms (avolition, blunted affect) vs placebo. Mechanism: NMDA glycine modulatory site agonism. Critical context: this finding has been replicated with mixed results; large definitive Phase 3 trials of glycinergic agents (sarcosine, glycine) for schizophrenia have been less impressive. CATIE-style trials of D-cycloserine (related mechanism) were negative. Modern schizophrenia treatment has not adopted high-dose glycine. Doses required are very large (30-60 g/day) — challenging for compliance.

6
Glycine for Viral Infection Prevention — Observational Study

3-year observational study in 127 volunteers prone to frequent viral infections. 85 received glycine 10 g/day; 42 controls. Outcomes: infection frequency. (2020 observational)

127 volunteers, observational design.

Glycine group reported fewer viral infections than controls. Critical caveat: not a randomized trial — observational; selection effects and recall bias likely. Evidence is weak. Should not be cited as established viral prevention.

7
Glycine for Tumor Biology — Animal Study

Animal study in rats with colorectal liver metastasis evaluating glycine alone or with FOLFOX chemotherapy. Outcomes: tumor volume, vascularization. (2020)

Rats — animal model, not clinical trial.

Glycine reduced tumor volume and vascularization in this animal model. Critical caveat: animal research — does not establish clinical relevance. Many cancer-relevant findings in animal models have not translated to human cancer treatment. Cancer patients should consult their oncologist before any supplementation; some supplements interfere with chemotherapy.

Side effects and drug interactions

Common Potential side effects

Gastrointestinal Issues:: Mild nausea, upset stomach, diarrhea, or soft stools. These are the most frequently reported side effects, typically occurring at doses above 10 g/day. Studies using 3–5 g/day (e.g., for sleep or metabolic benefits) report minimal gastrointestinal effects, comparable to placebo.
Drowsiness or Sedation:: Mild drowsiness or lethargy, particularly when taken in the evening for sleep benefits. Glycine’s calming effect on the nervous system (via glycine receptor activation) can cause drowsiness, which is often intentional for sleep improvement but may be undesirable during the day.

Important Drug interactions

Clozapine — glycine is a co-agonist at NMDA receptors; high-dose glycine (30–60 g/day) has been studied as adjunctive therapy for schizophrenia alongside clozapine; may enhance antipsychotic effects
NMDA receptor antagonists (ketamine, memantine, dextromethorphan) — glycine co-agonism at NMDA receptors may modulate effects of NMDA antagonists; complex interaction
Anticoagulants — glycine may mildly affect platelet aggregation at very high doses; monitor with warfarin at doses above 10 g/day

Frequently asked questions about Glycine

How much glycine should I take?

For sleep, studies use about 3 grams taken before bed. As a general amino acid supplement it is used at 3 to 5 grams per day. It is a sweet-tasting powder that dissolves easily in water.

Does glycine help with sleep?

Glycine taken before bed has been studied for improving sleep quality and helping people feel more rested, possibly by gently lowering core body temperature. Around 3 grams about an hour before bed is the studied approach.

When should I take glycine?

For sleep, take about 3 grams 30 to 60 minutes before bed. For general or daytime use, such as alongside collagen or for antioxidant support, timing is flexible and it can be taken any time of day.

Is glycine safe?

Glycine is an amino acid the body makes itself and is generally very well tolerated, with occasional mild digestive upset at higher doses. It is considered safe for most people at typical supplemental amounts.

What is Glycine?

Glycine is a non-essential amino acid found in protein-rich foods and synthesized by the body, playing a key role in collagen formation, neurotransmitter function, and muscle repair. As a dietary supplement, it is often used to improve sleep quality, reduce inflammation, and support joint and skin health.

What is Glycine used for?

Glycine is researched primarily for Muscle & Recovery and Sleep Health. Glycine may enhance sleep by reducing core body temperature and calming the nervous system. Studies suggest 3 grams taken before bed can improve sleep onset and quality, reducing daytime fatigue.

What is the recommended dosage of Glycine?

The clinically studied dose is 3–5 g/day for sleep quality; metabolic/detox: 5–10 g/day; collagen support: 3–5 g/day alongside proline; generally recognized as safe at up to 1 g/kg body weight Always follow the product label and check with a healthcare provider for personal advice.

Is Glycine safe, and does it have side effects?

For most healthy adults, Glycine is well tolerated at studied doses. Reported effects can include: Gastrointestinal Issues:: Mild nausea, upset stomach, diarrhea, or soft stools. These are the most frequently reported side effects, typically occurring at doses above 10 g/day. Studies using 3–5 g/day (e.g. It may also interact with some medications. Glycine is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does Glycine interact with any medications?

Possible interactions include: Clozapine — glycine is a co-agonist at NMDA receptors; high-dose glycine (30–60 g/day) has been studied as adjunctive therapy for schizophrenia alongside clozapine; may enhance antipsychotic effects NMDA receptor antagonists (ketamine, memantine, dextromethorphan) — glycine co-ag… 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 Moderate (3 out of 5). It is backed by 7 clinical trials and 8 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(8 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: Metabolic analysis: endogenous glycine synthesis (~3 g/day) plus typical dietary intake (1.5-3 g/day) falls short of collagen-synthesis demand by ~10 g/day in a 70-kg adult. Argues glycine should be considered semi-essential. Backs the page's collagen and joint-health benefit claim and supports the 3-5 g/day collagen-support dose recommendation.
  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: Crossover trial in healthy volunteers sleep-restricted to 75% of usual sleep for 3 nights: 3 g glycine before bedtime significantly reduced VAS fatigue and showed a trend toward reduced sleepiness the following day vs placebo. Backs the page's claim that 3 g pre-bed improves sleep quality and reduces daytime fatigue.
  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 pilot in older adults: GlyNAC substantially elevated intracellular glutathione, reduced oxidative stress, improved mitochondrial fuel oxidation, insulin sensitivity, endothelial function, muscle strength, and cognition vs placebo. Benefits disappeared 12 weeks after stopping — sustained treatment is required. Matches the page's trial card #3 framing of dose-response biomarker improvements.
  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 71): GlyNAC improved oxidative stress, glutathione deficiency, mitochondrial dysfunction, mitophagy, inflammation, insulin resistance, endothelial dysfunction, genomic damage, stem cell fatigue, and cellular senescence — alongside gains in muscle strength, gait speed, exercise capacity, waist circumference, and blood pressure. Directly matches the page's trial card #1; small sample, single research group (Sekhar lab) caveat applies.
  8. Vargas MH, Del-Razo-Rodríguez R, López-García A, Lezana-Fernández JL, Chávez J, Furuya MEY, Marín-Hernández A. 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.