Benefits
Gut Health Support
Strengthens the intestinal lining, potentially reducing "leaky gut" by supporting tight junction proteins. May alleviate symptoms of irritable bowel syndrome (IBS) or inflammatory bowel diseases like Crohn’s by reducing inflammation and promoting mucosal repair. Acts as a primary fuel source for enterocytes (gut cells), aiding in gut barrier maintenance.
Immune System Boost
Supports immune cell function, particularly lymphocytes and macrophages, which rely on glutamine for energy and proliferation. May reduce infection risk during periods of stress, illness, or intense physical activity by maintaining immune cell activity.
Muscle Recovery and Exercise Performance
Reduces muscle soreness and supports recovery after intense exercise by replenishing glutamine stores depleted during physical stress. May help preserve muscle mass during catabolic states (e.g., illness, fasting, or intense training). Some evidence suggests it aids hydration by improving electrolyte and water absorption in cells.
Wound Healing and Recovery from Injury
Promotes tissue repair and collagen synthesis, which can accelerate healing of wounds, burns, or surgical incisions. Used in clinical settings to support recovery in critically ill patients or those with trauma.
Brain Health and Cognitive Function
Serves as a precursor to neurotransmitters like glutamate and GABA, potentially supporting mental clarity and mood regulation.May reduce cravings for sugar or alcohol by stabilizing blood sugar and supporting brain function (anecdotal evidence).
Metabolic Health
May improve insulin sensitivity and glucose metabolism, though evidence is mixed and dose-dependent. Supports detoxification by aiding in ammonia clearance in the liver.
Mechanism of Action
Protein Synthesis and Cellular Function
L-Glutamine is a building block for proteins, contributing to tissue repair and muscle growth. It serves as a precursor for the synthesis of other amino acids, peptides (e.g., glutathione), and nucleotides, which are essential for cell division and repair.
Energy Source
L-Glutamine is a major fuel source for rapidly dividing cells, such as enterocytes (gut cells) and immune cells (e.g., lymphocytes). It is metabolized into alpha-ketoglutarate, feeding the Krebs cycle to produce ATP.
Gut Health
It maintains intestinal integrity by supporting the tight junctions of the gut lining, reducing permeability (e.g., "leaky gut"). It promotes the growth and repair of the intestinal mucosa, aiding conditions like inflammatory bowel disease or chemotherapy-induced damage.
Immune System Support
L-Glutamine is critical for immune cell proliferation and function, particularly for lymphocytes and macrophages. It supports the production of cytokines and antibodies, enhancing immune responses.
Nitrogen Transport and Acid-Base Balance
It acts as a nitrogen shuttle between tissues, facilitating ammonia detoxification in the liver via the urea cycle. It helps regulate acid-base balance in the kidneys by serving as a substrate for ammoniagenesis, aiding in acid excretion.
Antioxidant Support
L-Glutamine is a precursor to glutathione, a major antioxidant, which protects cells from oxidative stress and supports detoxification.
Muscle Recovery and Anti-Catabolism
In muscle tissue, L-glutamine reduces protein breakdown (catabolism) during stress, trauma, or intense exercise. It supports glycogen replenishment and hydration of muscle cells, aiding recovery.
Neurotransmitter Precursor
L-Glutamine is converted to glutamate, a key excitatory neurotransmitter, and subsequently to GABA, an inhibitory neurotransmitter, influencing brain function.
Clinical Trials
A Phase 3 Trial of L-Glutamine in Sickle Cell Disease
Study: A multicenter, randomized, placebo-controlled, double-blind, phase 3 trial (NCT01179217) enrolled 230 patients (aged 5–58 years) with sickle cell anemia or sickle β0-thalassemia, who had ≥2 pain crises in the prior year. Patients received oral pharmaceutical-grade L-glutamine (0.3 g/kg/dose, up to 30 g/day) or placebo twice daily for 48 weeks, with a 3-week tapering period. Patients on stable hydroxyurea continued treatment. The primary outcome was the number of sickle cell crises (pain requiring parenteral narcotics/ketorolac, chest syndrome, priapism, or splenic sequestration).
Findings: L-glutamine reduced the median number of pain crises (3 vs. 4 in the placebo group, p<0.05). It also decreased hospitalizations (median 2 vs. 3, p<0.05), reduced cumulative hospital days, and lowered the incidence of acute chest syndrome. Common side effects included constipation, nausea, headache, and abdominal pain, with a low discontinuation rate (2.7%). No significant safety concerns were noted. The FDA approved L-glutamine (Endari) for sickle cell disease in 2017 based on these results.
Link: https://pubmed.ncbi.nlm.nih.gov/30021096/
A Systematic Review and Meta-Analysis of Clinical Trials on the Effects of Glutamine Supplementation on Gut Permeability in Adults
Study: This 2024 meta-analysis (PRISMA protocol) reviewed 10 randomized placebo-controlled trials (1998–2014) with 352 participants (mean age 46.52 years) to assess L-glutamine’s impact on intestinal permeability. Studies included various health conditions (e.g., Crohn’s disease, chemotherapy-induced mucositis). Glutamine was administered orally (doses ≥30 g/day or <30 g/day) for varying durations. Gut permeability was measured using lactulose/mannitol ratio (LMR) or 51Cr-EDTA methods. Statistical analysis used weighted mean differences (WMD) with a random effects model.
Findings: Overall, glutamine supplementation did not significantly reduce intestinal permeability (WMD: -0.00, 95% CI: -0.04, 0.03). However, subgroup analysis showed significant reductions with high doses (>30 g/day) for <2 weeks (WMD: -0.01, 95% CI: -0.10, -0.08) and in studies with sample sizes <20 or using LMR. No publication bias was detected (Egger’s test, p=0.460). The study suggests short-term, high-dose glutamine may improve gut barrier function in specific contexts.
Link: https://link.springer.com/article/10.1007/s00726-024-03420-0
A Comprehensive Insight into the Effect of Glutamine Supplementation on Metabolic Variables in Diabetes Mellitus: A Systematic Review
Study: This 2020 systematic review evaluated 19 studies (10 animal, 9 human) from 1482 articles, assessing L-glutamine’s effects on metabolic variables in diabetes mellitus. Databases (PubMed, SCOPUS, Embase, ProQuest, Google Scholar) were searched through April 2020. Studies included clinical trials and animal models, focusing on outcomes like glycemic control, incretin hormones (GLP-1, GIP), lipid profiles, oxidative stress, and inflammation. Quality was assessed using the PEDro scale.
Findings: Nine studies reported significant increases in serum GLP-1 levels. Eight studies showed reductions in fasting blood sugar, four in postprandial blood sugar, and four in triglycerides. Seven studies noted increased insulin production, but HbA1c effects were inconclusive. Glutamine showed promise for weight reduction, oxidative stress, and inflammation, but more precise trials are needed. No major adverse effects were reported.
Link: https://nutritionandmetabolism.biomedcentral.com/articles/10.1186/s12986-020-00489-4
A Randomized Trial of Glutamine and Antioxidants in Critically Ill Patients (REDOXS)
Study: A 2013 blinded, 2x2 factorial, randomized controlled trial (NCT00133978) evaluated glutamine and antioxidant supplementation in 1,218 critically ill patients with organ dysfunction. Patients received glutamine (0.35 g/kg/day enterally or parenterally) or placebo within 24 hours of ICU admission, primarily via enteral nutrition. Outcomes included in-hospital mortality, 6-month mortality, organ failure, infections, and hospital length of stay (LOS).
Findings: Glutamine supplementation increased in-hospital mortality (32.4% vs. 27.2% in non-glutamine, p<0.05) and 6-month mortality. It also extended ICU and hospital LOS without affecting organ failure or infection rates. The study did not consistently find glutamine deficiency in patients, challenging the hypothesis that supplementation benefits critically ill patients. High-dose glutamine was associated with harm in this population, particularly those with multiorgan failure.
Link: https://www.nejm.org/doi/full/10.1056/NEJMoa1212722
The Effect of Glutamine Supplementation on Serum Levels of Some Inflammatory Factors, Oxidative Stress, and Appetite in COVID-19 Patients
Study: A 2021 case-control study included 452 COVID-19 patients with respiratory involvement (222 received L-glutamine, 230 controls). The case group consumed 30 g/day (10 g three times daily) for 5 days. Outcomes included serum levels of inflammatory markers (IL-1β, TNF-α, hs-CRP), oxidative stress markers (malondialdehyde, total antioxidant capacity), appetite, hospitalization duration, ICU need, and mortality.
Findings: Glutamine significantly reduced IL-1β, TNF-α, hs-CRP, and malondialdehyde (p<0.05) while increasing total antioxidant capacity and appetite (p<0.05). Hospitalization duration was shorter (10.5 vs. 14.3 days, p=0.015), ICU need was lower (p=0.008), and mortality was reduced (3.47% in controls vs. none reported in glutamine group, p<0.05). No significant adverse effects were noted.
Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC7883760/
Potential Side Effects
Gastrointestinal
Bloating, gas, nausea, or mild abdominal discomfort.
Headache
Some users report mild headaches, particularly at higher doses.
Fatigue or Dizziness
Occasional reports of tiredness or lightheadedness.