NutriDex

The Supplement Research Compendium
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Glutamine

L-Glutamine

Abundant amino acid sold for gut, immunity and recovery.

Mixed evidence ⚡Performance🛡️Gut & Immune

✚ Updated · How we grade evidence

Evidence tier
Mixed
Research weight
Citations
8 verified / 8
Classification
Performance
❝
What the evidence says. Graded mixed: glutamine is a genuine, FDA-approved drug for sickle cell disease, but for the way it is actually marketed — muscle recovery, immunity, and 'leaky gut' in healthy people — meta-analyses are largely null, and high-dose IV glutamine increased mortality in critically ill patients. (Mixed evidence: Conflicting results across studies; benefit uncertain.)

What is Glutamine?

Glutamine (L-Glutamine) is a performance supplement used for reduces sickle cell pain crises (rx). NutriDex grades the human evidence as Mixed. Glutamine is the most abundant free amino acid in the body and a fuel for gut and immune cells, which drives its supplement marketing. The evidence splits sharply. Pharmaceutical L-glutamine (Endari) is FDA-approved for sickle cell disease, where a phase-3 RCT cut pain crises ~25% and hospitalizations ~33%. In surgery, meta-analyses show fewer infections and shorter stays. But for popular fitness and wellness claims the data are weak: a meta-analysis of athletes found no effect on immune markers, VO2max or body composition, and high doses reduced intestinal permeability only modestly during heat-stress running. High-dose intravenous glutamine actually increased mortality in critically ill patients (REDOXS). Healthy, well-fed people make plenty of their own glutamine, so routine supplementation for recovery or 'gut healing' has little proven benefit. The clinical value is real but narrow and prescription-bound.

Purported Benefits

✓Reduces sickle cell pain crises (Rx)
✓May lower exercise gut permeability
✓Post-surgical immune support
✓Modest eccentric-exercise recovery

Evidence by outcome

The same supplement can be well-proven for one use and unproven for another — here is the human evidence graded outcome by outcome.

OutcomeEvidenceEffectStudies
Sickle cell pain crises (prescription Endari)Single phase-3 RCT cut crises ~25% and hospitalizations ~33%; basis for FDA approval. Moderate ↑ benefit · moderate 1
Post-surgical infections & recovery31-RCT meta-analysis in colorectal surgery showed fewer infections and leaks; benefit confined to catabolic states. Moderate ↑ benefit · moderate 1
Exercise gut permeabilityNo overall effect in meta-analysis; reduction only at very high doses/short term and during heat-stress running. Mixed ↔ mixed · small 2
Athletic immune/body-composition outcomes25-trial meta-analysis found no effect on immune cells, VO2max, fat or lean mass in athletes. Moderate — no effect · negligible 1
Eccentric-exercise recoverySmall crossover RCT (n=16) preserved torque and modestly reduced soreness; needs replication. Preliminary ↑ benefit · small 1
Mortality in critically ill patientsEnteral glutamine did not reduce mortality/infections; high-dose IV increased mortality elsewhere. Moderate — no effect · negligible 1

Dosing & Compounds

Typical Dose
Recovery/gut studies use 0.1–0.3 g/kg (roughly 5–30 g/day); the FDA-approved sickle-cell drug Endari is 0.3 g/kg twice daily.
Active Compounds
L-glutamine (free amino acid)Alanyl-glutamine (dipeptide form)

Safety & Cautions

Oral glutamine is well tolerated up to ~30 g/day; mild bloating, nausea or constipation can occur. Avoid in people with cirrhosis or hepatic encephalopathy, since glutamine raises ammonia. Do not assume IV/high-dose safety: in the REDOXS trial high-dose intravenous glutamine increased mortality in critically ill patients with renal or multi-organ failure. It may blunt some anti-seizure and chemotherapy effects and can lower the lactulose used as a laxative/ammonia treatment; discuss with a clinician if you take antiepileptics, are on cancer therapy, or have kidney or liver disease. Educational only — always check with your doctor or pharmacist before combining Glutamine with any medicine.

Key Studies

Meta-analysis Abbasi 2024 ✓ PubMed
Meta-analysis (10 trials, 428 adults): no overall effect on gut permeability; significant reduction only at >30 g/day and <2 weeks of use.
Meta-analysis Yang 2021 ✓ PubMed
Meta-analysis (31 RCTs, 2201 colorectal-surgery patients): glutamine raised immunoglobulins and cut infections and anastomotic leakage vs control.
Meta-analysis Ramezani Ahmadi 2019 ✓ PubMed
Meta-analysis (25 trials): glutamine had no effect on athletes' immune cells, VO2max, fat or lean mass, CK or glucose; only modest weight reduction.
Meta-analysis van Zanten 2015 ✓ PubMed
Meta-analysis (11 trials, 1079 critically ill): enteral glutamine did not reduce mortality or infections, though hospital stay was ~4.7 days shorter.
RCT Niihara 2018 ✓ PubMed
Phase-3 RCT (NEJM): L-glutamine cut median sickle-cell pain crises 25% (3 vs 4) and hospitalizations 33% over 48 weeks; basis for FDA approval.
RCT Pugh 2017 ✓ PubMed
RCT: oral glutamine before running in the heat lowered lactulose:rhamnose permeability dose-dependently (~25% at 0.25 g/kg, ~40% at 0.9 g/kg).
RCT Legault 2015 ✓ PubMed
Crossover RCT (n=16): 0.3 g/kg/day glutamine preserved knee-extensor torque (90% vs 79%) and modestly reduced soreness over 96 h after eccentric exercise.
Review Cruzat 2018 ✓ PubMed
Review of glutamine metabolism, immune/gut function and clinical use; details why benefit is largely confined to catabolic, depleted states.
8 sources cited · 8 verified Search all studies on PubMed ↗

Common questions about Glutamine

What is Glutamine used for?

Glutamine is most often taken for Reduces sickle cell pain crises (Rx), May lower exercise gut permeability, Post-surgical immune support, Modest eccentric-exercise recovery. Abundant amino acid sold for gut, immunity and recovery.

Does Glutamine work — what does the evidence say?

Mixed evidence. Conflicting results across studies; benefit uncertain. Glutamine is the most abundant free amino acid in the body and a fuel for gut and immune cells, which drives its supplement marketing. The evidence splits sharply. Pharmaceutical L-glutamine (Endari) is FDA-approved for sickle cell disease, where a phase-3 RCT cut pain crises ~25% and hospitalizations ~33%. In surgery, meta-analyses show fewer infections and shorter stays. But for popular fitness and wellness claims the data are weak: a meta-analysis of athletes found no effect on immune markers, VO2max or body composition, and high doses reduced intestinal permeability only modestly during heat-stress running. High-dose intravenous glutamine actually increased mortality in critically ill patients (REDOXS). Healthy, well-fed people make plenty of their own glutamine, so routine supplementation for recovery or 'gut healing' has little proven benefit. The clinical value is real but narrow and prescription-bound.

What is the typical dose of Glutamine?

Recovery/gut studies use 0.1–0.3 g/kg (roughly 5–30 g/day); the FDA-approved sickle-cell drug Endari is 0.3 g/kg twice daily.

Is Glutamine safe? Any cautions or side effects?

Oral glutamine is well tolerated up to ~30 g/day; mild bloating, nausea or constipation can occur. Avoid in people with cirrhosis or hepatic encephalopathy, since glutamine raises ammonia. Do not assume IV/high-dose safety: in the REDOXS trial high-dose intravenous glutamine increased mortality in critically ill patients with renal or multi-organ failure. It may blunt some anti-seizure and chemotherapy effects and can lower the lactulose used as a laxative/ammonia treatment; discuss with a clinician if you take antiepileptics, are on cancer therapy, or have kidney or liver disease.

How many studies support Glutamine?

NutriDex cites 8 sources for Glutamine, graded "Mixed".

Cite this page
APA

Peh, D. (2026). Glutamine (L-Glutamine): Benefits, Dosage, Side Effects & Evidence. NutriDex — The Supplement Research Compendium. Retrieved 26 Jun 2026, from https://nutridex.info/s/l-glutamine

BibTeX
@misc{nutridex_l_glutamine,
  author       = {Peh, Daryl},
  title        = {Glutamine (L-Glutamine): Benefits, Dosage, Side Effects \& Evidence},
  year         = {2026},
  howpublished = {NutriDex --- The Supplement Research Compendium},
  url          = {https://nutridex.info/s/l-glutamine},
  note         = {Reviewed by Dr Daryl Peh, MBBS Singapore, MMed FM. Accessed 2026-06-26}
}

For medical claims, citing the underlying primary studies linked above is preferred. NutriDex is an educational reference, not medical advice.

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