tuneTypical Dose
5,000–10,000 mg/day (outpatient, evidence-poor context)
Amino Acid
L-Glutamine
L-2-amino-4-(carbamoylamino)butanoic acid
Evidence TierCWADA NOT PROHIBITED
watchEffect Window
2–12 weeks
check_circleCompliance
WADA NOT PROHIBITED
Overview
Clinical Summary
L-glutamine is a conditionally essential amino acid used by gut and immune cells. It is used for gut barrier support and recovery during physiologic stress, with mixed benefits in healthy athletes.
In clinical and high-stress states, glutamine supports gut mucosal integrity and immune function, with evidence for reduced intestinal permeability in select contexts. Athletic performance benefits are mixed, with stronger effects during extreme training or illness stress. Minority studies report symptom reductions in IBS subgroups and chemotherapy-related mucositis. Effects are condition dependent and generally modest in healthy individuals.
Conditionally essential in catabolic stress, supports enterocyte and immune cell substrate utilization. Routine anabolic claims in healthy users are not strongly supported.
Outcomes
What This Is Expected To Influence
Primary Outcomes
- No clear performance or body-composition benefit in athletes/healthy adults.
- No overall mortality/LOS benefit in mixed critically ill populations.
- Context-specific possible benefit in selected burn cohorts for wound outcomes.
Secondary Outcomes
- Mixed/insufficient evidence for intestinal permeability endpoints in GI disease populations.
- Weak evidence for muscle-building claims in healthy adults.
Safety
Contraindications and Interactions
Contraindications
- Pregnancy
- Lactation
- Renal/hepatic insufficiency
- Unstable critical illness
- Active sepsis without specialist oversight
Side effects
- Generally well tolerated
- Bloating at high doses
Interactions
- Caution with nephrotoxic and complex critical-care regimens
Avoid if
- Renal failure
- Hepatic failure
- Active severe organ dysfunction
Evidence
Study-level References
l-glutamine-SRC-001Systematic review and meta-analysis of clinical trials
Sourceopen_in_newAhmadi ER et al., Clin Nutr 2019;38(3):1076-1091. DOI: 10.1016/j.clnu.2018.05.001 (PMID 29784526)
Population: Adults >18 in athletic populations (25 trials in meta-analysis)
Dose protocol: Heterogeneous dosing, includes oral supplementation regimens >200 mg/kg in subgroup analyses
Key findings: No reliable effect on athletic immune function, aerobic performance, or body composition. Modest pooled weight reduction (WMD -1.36, 95% CI -2.55 to -0.16).
Notes: Trial heterogeneity in formulations, dosing, blinding, and reporting.
Paper content
No reliable effect on athletic immune function, aerobic performance, or body composition; modest pooled weight reduction (WMD -1.36, 95% CI -2.55 to -0.16).
l-glutamine-SRC-002Meta-analysis of RCTs
Sourceopen_in_newChen QH et al., Crit Care 2014;18(1):R8. DOI: 10.1186/cc13185 (PMID 24401636)
Population: Critically ill adults, 18 trials; 3383 patients for mortality, 2862 for infection outcomes
Dose protocol: Enteral/parenteral glutamine with mixed doses
Key findings: No overall mortality/LHS benefit. Infection incidence reduced in pooled analyses (RR 0.85). Mortality increased in high-dose subgroup (>0.5 g/kg/day) with RR 1.18 (95% CI 1.02–1.38).
Notes: Clinical practice variation over time, mixed nutrition backgrounds. Subgroup interpretation vulnerable to confounding.
Paper content
No overall mortality/LHS benefit; infection incidence reduced in pooled analyses (RR 0.85). Mortality increased in high-dose subgroup (>0.5 g/kg/day) with RR 1.18 (95% CI 1.02–1.38).
l-glutamine-SRC-003Systematic review and meta-analysis
Sourceopen_in_newTao W et al., J Burn Care Res 2024;45(3):675-684. DOI: 10.1093/jbcr/irae007 (PMID 38243579)
Population: Burn patients across RCTs; 22 trials, 2170 participants
Dose protocol: Short-course inpatient glutamine supplementation (varied dose/route)
Key findings: Wound/infection outcomes improved (infection RR 0.38), LOS and wound healing time improved. No in-hospital mortality signal. Recommendations not routine due small-study dependence.
Notes: High between-trial heterogeneity and possible small-center effects limit certainty.
Paper content
Wound/infection outcomes improved (infection RR 0.38), LOS and wound healing time improved; no in-hospital mortality signal; recommendations not routine due small-study dependence.
l-glutamine-SRC-004Randomized controlled trial
Sourceopen_in_newDen Hond E et al., JPEN J Parenter Enteral Nutr 1999;23(1):7-11. DOI: 10.1177/014860719902300107 (PMID 9888411)
Population: Adults with Crohn disease and raised permeability (n=14 randomized)
Dose protocol: 7 g oral glutamine three times daily for 4 weeks
Key findings: No significant restoration of intestinal permeability or inflammatory/nutritional markers.
Notes: Very small sample size and disease-specific, legacy trial period.
Paper content
No significant restoration of intestinal permeability or inflammatory/nutritional markers.
l-glutamine-SRC-005Practice guideline
Sourceopen_in_newESPEN guideline on clinical nutrition in the intensive care unit, 2019; DOI:10.1016/j.clnu.2018.08.037 and 2023 update DOI:10.1016/j.clnu.2023.07.011
Population: Critically ill adults across multiple guideline-consensus domains
Dose protocol: ICU nutrition recommendations, including glutamine indications/limitations
Key findings: Supports selective/limited glutamine use. Emphasizes that routine supplementation is not broadly recommended in ICU populations.
Notes: Recommendations reflect pooled/clinical evidence and expert consensus. May lag publication timing in rapidly evolving ICU literature.
Paper content
Supports selective/limited glutamine use; emphasizes that routine supplementation is not broadly recommended in ICU populations.
l-glutamine-SRC-006Systematic review and meta-analysis.
Sourceopen_in_newArribas-Lopez E, Zand N, Ojo O, Snowden MJ, Kochhar T. The Effect of Amino Acids on Wound Healing: A Systematic Review and Meta-Analysis on Arginine and Glutamine. Nutrients. 2021;13(8):2498. doi:10.3390/nu13082498. PMID:34444657.
Population: Human subjects across multiple wound-healing studies.
Dose protocol: Glutamine supplementation at various doses and routes in wound-healing populations (multiple trials pooled).
Key findings: Pooled mortality OR 0.48 favoring glutamine. Hospital LOS reduced by 2.65 days. Significant IL-6 and TNF-alpha reductions. Improved nitrogen balance and gut permeability.
Notes: Mixed surgical and critical-care populations with heterogeneous dosing. Supports conditionally essential role in wound healing contexts.
Paper content
This systematic review and meta-analysis examined glutamine (and arginine) supplementation for wound healing. For glutamine specifically, pooled results showed significant improvements in nitrogen balance, reductions in IL-6 and TNF-alpha, improved gut permeability, lower mortality (OR 0.48), reduced CRP, and shorter hospital stays (MD -2.65 days). The findings support glutamine as a conditionally essential nutrient in wound-healing contexts, particularly surgical and critical-care populations. However, the included studies varied considerably in dose, route, and patient populations, limiting the precision of dose recommendations.
l-glutamine-SRC-007Systematic review and meta-analysis of randomized placebo-controlled trials
Sourceopen_in_newAbbasi F, Haghighat Lari MM, Khosravi GR, Mansouri E, Payandeh N, Milajerdi A. A systematic review and meta-analysis of clinical trials on the effects of glutamine supplementation on gut permeability in adults. Amino Acids. 2024;56(1):60. PMID:39397201.
Population: Adults enrolled in clinical trials evaluating oral glutamine and gut permeability.
Dose protocol: Oral glutamine at varying doses across placebo-controlled RCTs (352 participants).
Key findings: No significant overall effect on intestinal permeability. Modest benefit in high-dose (>30 g/day) short-duration subgroup only.
Notes: Important null result for calibrating gut-permeability supplementation claims. Typical supplement doses not convincingly supported.
Paper content
Modern pooled human evidence suggests glutamine can improve gut-permeability markers in adults, but the signal is context-specific and heterogeneous rather than a universal performance or wellness effect.