Glycylglutamine
Also known as: Gly-Gln, Glycyl-L-glutamine, Glycylglutamine dipeptide, H-Gly-Gln-OH
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Summary
Glycylglutamine is a dipeptide comprising glycine and glutamine that serves as a stable source of glutamine when added to parenteral nutrition. It has been investigated primarily in surgical and oncology settings to support protein metabolism, improve nitrogen balance, and reduce postoperative complications.
Mechanism of Action
After intravenous infusion, glycylglutamine is taken up by tissues, especially kidney and liver, where peptide transporters mediate cellular entry. Intracellular peptidases cleave the dipeptide, releasing free glutamine and glycine. The liberated glutamine supplies nitrogen for protein synthesis, supports ribosomal maintenance in muscle, and fuels hepatic gluconeogenesis and renal ammoniagenesis, thereby helping to preserve muscle protein synthesis and overall nitrogen balance.
What the Research Shows
Small clinical trials and meta‑analyses of randomized controlled studies have examined glycylglutamine‑supplemented parenteral nutrition. In peri‑operative patients, supplementation maintained ribosomal concentrations and muscle protein synthesis during the infusion period (n=9 vs 8 controls). Meta‑analyses of 14–16 trials (587–773 patients) reported reduced infectious complication rates (RR≈0.5–0.7) and shorter hospital stays (≈3–5 days) compared with standard nutrition, alongside improved cumulative nitrogen balance. In acute myeloid leukaemia patients receiving intensive chemotherapy, glycylglutamine accelerated neutrophil recovery (P=0.04) but did not affect fever duration. A metabolic study showed efficient tissue removal, renal predominance in clearance, and no alteration in plasma glucose or ammonia during infusion. A review lists glycylglutamine as a candidate respiratory stimulant, but no efficacy data are presented.
Reported Benefits
Evidence from peri‑operative trials suggests glycylglutamine can preserve muscle protein synthesis during short‑term infusion, improve nitrogen balance, shorten hospital stays, and lower postoperative infection rates. In chemotherapy patients, it may hasten neutrophil recovery. These benefits appear most reliable in the context of short‑term parenteral nutrition for surgical or intensive‑care populations.
Limitations of the Evidence
The data are confined to short‑term intravenous supplementation in specific clinical settings; oral use has not been studied. Sample sizes are modest, and many trials combine glycyl‑ and alanyl‑glutamine, making it hard to isolate glycylglutamine’s effect. Long‑term safety, efficacy in chronic disease, and impact on mortality remain unproven. No regulatory approval for therapeutic use has been reported.
Safety Considerations
Published studies report glycylglutamine to be well tolerated, with no increase in adverse events, no changes in plasma glucose, and no excess ammonia production during infusion. However, safety data are limited to short‑term use in hospitalized patients; caution is advised in renal impairment given the kidney’s role in clearance. Chronic or high‑dose safety has not been established.
How It Is Administered
Glycylglutamine is administered intravenously as part of total parenteral nutrition admixtures, typically providing about 20 g of glutamine equivalents per day. Oral formulations have been mentioned but lack clinical evaluation. The peptide is supplied as a sterile solution or powder for reconstitution and added to the nutrient bag before infusion.
Routes of Administration
Goals & Uses
- Antioxidant support (glutathione precursor)Oxidative StressLow
- Intestinal mucosal integrityGastrointestinal HealthModerate
- Glutamine supplementation in critical illnessClinical Nutrition / ICU SupportModerate
- Parenteral nutrition glutamine sourceClinical NutritionModerate
- Immune function supportImmunologyLow
Contraindications
- Severe renal failureRenal ImpairmentHigh
- Severe hepatic failureHepatic ImpairmentHigh
- Hypersensitivity to glutamine or glycineAllergyHigh
Adverse Effects
- Elevated blood urea nitrogenMetabolicUncommon
- NauseaGastrointestinalUncommonFeeling of sickness or urge to vomit
- HyperammonemiaMetabolicRare
Drug Interactions
- Lactulose / ammonia-lowering agentsModerate
Population Constraints
- Patients with inborn errors of amino acid metabolismGenetic/metabolicAbsolute
- Pediatric patientsAgeRelative
- Pregnant or lactating womenReproductiveRelative
Regulatory Status
- European UnionUnapprovedNot EMA-approved. Used in research contexts.
- United StatesUnapprovedNot FDA-approved as a drug. May be used as a research compound or dietary supplement ingredient.
- United KingdomUnapprovedNot MHRA-approved as a medicinal product.
Not independently approved by FDA, EMA, or other major regulatory agencies as a drug. Used primarily in research settings. Related glutamine dipeptides (e.g., alanyl-glutamine) have broader clinical use. Glycylglutamine may be available as a research chemical or nutritional supplement ingredient.
Evidence & Sources
- Journal ArticleModeratePetersson B, et al.1994-01-01T00:00:00.000000Z
- Journal ArticleModerateDahan A, et al.2018-01-01T00:00:00.000000Z
- Journal ArticleHighYue C, et al.2013-01-01T00:00:00.000000Z
- Journal ArticleHighWang Y, et al.2010-01-01T00:00:00.000000Z
- Journal ArticleModerateScheid C, et al.2004-01-01T00:00:00.000000Z
- Journal ArticleModerateAdibi SA, et al.1993-01-01T00:00:00.000000Z
Frequently Asked Questions
What is glycylglutamine?
Glycylglutamine is a dipeptide made of glycine linked to glutamine. It is used as a stable glutamine source in intravenous nutrition formulas to support protein synthesis and nitrogen balance.
How is glycylglutamine given to patients?
In the studies, it is added to total parenteral nutrition solutions and infused intravenously, usually delivering around 20 g of glutamine per day. Oral use has not been clinically evaluated.
What clinical situations has glycylglutamine been studied in?
Research has focused on peri‑operative patients undergoing abdominal surgery, intensive‑care surgical patients, and adults with acute myeloid leukaemia receiving high‑dose chemotherapy, mainly to improve protein metabolism and reduce infection.
Is glycylglutamine an approved drug?
No. Glycylglutamine is classified as a research‑stage compound and is not approved as a medication for any indication.
Are there any safety concerns with glycylglutamine?
Short‑term studies report good tolerability and no metabolic disturbances, but data are limited to hospitalized patients. Caution is advised in people with kidney dysfunction, and long‑term safety has not been established.
What is Glycylglutamine used for?
Glycylglutamine is educationally associated with: Antioxidant support (glutathione precursor), Intestinal mucosal integrity, Glutamine supplementation in critical illness, Parenteral nutrition glutamine source, Immune function support. Educational only — not medical advice.
How is Glycylglutamine administered?
Recorded routes of administration: Intravenous, Oral.
What are the potential side effects of Glycylglutamine?
Reported adverse effects include: Elevated blood urea nitrogen, Nausea, Hyperammonemia. This list is not exhaustive — consult a qualified clinician.
Who should avoid Glycylglutamine?
Recorded contraindications: Severe renal failure, Severe hepatic failure, Hypersensitivity to glutamine or glycine. Consult a qualified clinician before use.