L-glutamine is an amino acid that the body makes on its own and also gets from dietary protein. It is the most abundant amino acid in the body, and immune cells consume it at high rates. As a supplement it is marketed to athletes for muscle recovery, immune support and “gut health.”
It is also a prescription drug. Under the brand name Endari, oral L-glutamine powder has been FDA-approved since 2017 to reduce the acute complications of sickle cell disease. The approved use rests on one phase 3 trial, and the European Medicines Agency judged the same data insufficient. For the claims made about supplements in healthy, well-fed people, the controlled trials are mostly negative.
This page keeps the prescription use and the supplement claims apart, and summarizes what the FDA labels, clinical trials and regulators report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Class | Amino acid (conditionally essential) |
| Prescription brands | Endari (NDA 208587, approved July 2017); generics since 2024; NutreStore (NDA 021667, 2004, discontinued) |
| Approved indication | Acute complications of sickle cell disease, ages 5 and up (Endari) |
| Route and strength | Oral powder, 5 g per packet |
| Labeled dose (Endari) | 5–15 g twice daily by body weight (10–30 g/day) |
| Half-life (label) | About 1 hour after an IV dose |
| Supplement status | Sold in the US as a dietary supplement ingredient; not a controlled substance |
| WADA status | Not on the 2026 Prohibited List |
What it is
L-glutamine is chemically (S)-2,5-diamino-5-oxopentanoic acid, the amide of glutamic acid: formula C₅H₁₀N₂O₃, molecular weight 146.15 g/mol (Endari label). Besides being built into proteins, it feeds into the production of glutamate, nucleotides and amino sugars.
A review in Nutrients describes glutamine as the most abundant and versatile amino acid in the body (Cruzat et al., Nutrients 2018). The review makes several points:
- Its supply to the blood is controlled mainly by skeletal muscle, the liver and the gut.
- Immune cells use it at a rate similar to or greater than glucose.
- Healthy people make enough of it, but during severe illness, injury or other catabolic (tissue-breakdown) states it can become essential. This is why it is called “conditionally essential.”
How it is thought to work in sickle cell disease
The Endari label states that the mechanism is not fully understood. Sickle red blood cells are more prone to oxidative damage than normal cells, which may contribute to their breakdown (hemolysis) and to the blocked blood vessels behind pain crises. The proposed mechanism is that L-glutamine improves the balance of NAD+ and NADH, molecules that protect red cells from oxidative damage, by increasing the supply of reduced glutathione (Endari label).
Pharmacokinetics
The Endari label summarizes published kinetic studies:
| Parameter | Finding |
|---|---|
| Peak level after a single 0.1 g/kg oral dose | Mean 1028 µM (150 mcg/mL), at about 30 minutes |
| Higher oral doses (0.1, 0.3 and 0.6 g/kg) | Peaks rise less than in proportion to dose, suggesting saturable absorption |
| Accumulation with twice-daily dosing | None |
| Effect of food | No significant change |
| Apparent volume of distribution | About 750 mL/kg |
| Terminal half-life (IV bolus) | About 1 hour |
| Urinary excretion | Under 0.3% of the dose; metabolism is the main route of removal |
Because the body breaks it down quickly and uses it for its own metabolism, oral glutamine does not build up in the blood with repeated dosing. No drug interaction studies have been done, and the kinetics have not been studied in kidney or liver impairment.
Approved medical use
Endari for sickle cell disease
Endari is indicated “to reduce the acute complications of sickle cell disease” in adults and children 5 years and older (Endari label). FDA approved it on July 7, 2017 (Drugs@FDA, NDA 208587). The first generic L-glutamine oral powder referenced to it was approved in July 2024 (Drugs@FDA, ANDA 215647).
The labeled dose is given twice daily, mixed into a cold or room-temperature drink or soft food:
| Body weight | Per dose | Per day |
|---|---|---|
| Under 30 kg | 5 g (1 packet) | 10 g |
| 30–65 kg | 10 g (2 packets) | 20 g |
| Over 65 kg | 15 g (3 packets) | 30 g |
The label lists no contraindications.
NutreStore for short bowel syndrome (discontinued)
The same molecule was first approved in 2004 as NutreStore, for short bowel syndrome (a malabsorption condition after loss of much of the small intestine). It was approved only together with recombinant human growth hormone (HGH) and a specialized diet (NutreStore label). The labeled dose was 30 g/day, taken as 5 g six times a day, for up to 16 weeks.
In the supporting trial, 41 patients dependent on intravenous nutrition were randomized to three arms. After 4 weeks, growth hormone plus glutamine cut weekly IV nutrition volume by 7.7 L, compared with 5.9 L for growth hormone alone (p = 0.023). Glutamine without growth hormone cut it by 3.8 L. NutreStore is now listed as discontinued (Drugs@FDA, NDA 021667).
Europe
Emmaus Medical applied to the European Medicines Agency to market the same product as Xyndari for sickle cell disease. EMA recommended refusal, judging that the main study did not show it reduced crises or hospital visits (EMA, Xyndari). EMA’s main concerns were:
- many patients dropped out, more of them on glutamine than on placebo, and the way their missing data were handled was not appropriate;
- the supportive trial was small, also had many early dropouts, and more patients on glutamine than on placebo were taking hydroxyurea.
The company withdrew the application on September 18, 2019, during re-examination, citing a change in marketing strategy.
What the research shows
Sickle cell disease (prescription use)
The pivotal phase 3 trial randomized 230 patients aged 5–58 with sickle cell anemia or sickle β⁰-thalassemia, each with 2 or more pain crises in the prior year, 2:1 to L-glutamine or placebo for 48 weeks (Niihara et al., NEJM 2018). The dose was 0.3 g/kg twice daily. About two thirds of patients in both groups stayed on hydroxyurea. The trial was funded by the manufacturer.
Results, as reported in the FDA label:
| Outcome over 48 weeks | L-glutamine (n = 152) | Placebo (n = 78) |
|---|---|---|
| Median number of sickle cell crises | 3 | 4 |
| Median hospitalizations for sickle cell pain | 2 | 3 |
| Median cumulative days in hospital | 6.5 | 11 |
| Median time to first crisis | 84 days | 54 days |
| Patients with acute chest syndrome | 8.6% | 23.1% |
The hazard ratio for time to first crisis was 0.69 (95% CI 0.52–0.93). A recurrent-event analysis gave a rate ratio of 0.75 (95% CI 0.62–0.90), about 25% fewer crises over the 48 weeks. A second method gave a wider interval that crossed 1 (95% CI 0.55–1.01) (Endari label).
A 2019 systematic review found three eligible studies of L-glutamine in sickle cell disease and noted conflicting results, small samples, lack of blinding and baseline differences in some of them. It concluded that only one randomized trial gives strong support for the approved indication (Cieri-Hutcherson et al., Pharmacotherapy 2019).
The sickle cell results apply to pharmaceutical-grade L-glutamine given under medical supervision for a specific disease. They do not show benefits of glutamine supplements in people without sickle cell disease.
Muscle mass and strength (supplement claim)
Glutamine is often sold as “anti-catabolic,” meaning it is claimed to reduce muscle breakdown. Controlled trials in healthy people do not support this.
In a double-blind trial, 31 young adults did 6 weeks of whole-body resistance training while taking glutamine (0.9 g per kg of lean tissue mass per day) or a maltodextrin placebo (Candow et al., Eur J Appl Physiol 2001):
| Measure | Glutamine (n = 17) | Placebo (n = 14) |
|---|---|---|
| Squat 1RM | About +30% | About +30% |
| Bench press 1RM | About +14% | About +14% |
| Lean tissue mass | +2% | +1.7% |
| Urinary 3-methylhistidine (marker of muscle protein breakdown) | +41% | +56% |
None of the differences between groups were significant. The authors concluded that glutamine had no effect on performance, body composition or muscle protein breakdown.
A 2019 meta-analysis of trials in adult athletes included 47 studies in the review and 25 in the pooled analysis (Ramezani Ahmadi et al., Clin Nutr 2019). It found:
- no effect on lean body mass, body fat percentage or aerobic capacity (VO₂max);
- a small greater reduction in body weight (weighted mean difference −1.36, 95% CI −2.55 to −0.16);
- no overall effect on immune cell counts, apart from fewer neutrophils at doses above 200 mg/kg.
Muscle soreness and recovery (supplement claim)
One small crossover trial in 16 healthy young adults tested 0.3 g/kg/day of glutamine or placebo for 72 hours after a bout of damaging eccentric (lengthening) knee-extension exercise (Legault et al., Int J Sport Nutr Exerc Metab 2015). Glutamine was associated with faster recovery of peak torque at one test speed and lower soreness ratings, for example 1.7 vs 2.9 at 72 hours. The effect on force recovery appeared larger in men. This is a single small study and has not been confirmed by larger trials.
Immune function in athletes (supplement claim)
Plasma glutamine falls after prolonged exercise and heavy training, which led to the idea that supplements could prevent exercise-related immune suppression. A review of the dosing and efficacy data concluded that supplements can keep plasma glutamine steady during and after hard exercise but do not prevent the post-exercise changes in immune function (Gleeson, J Nutr 2008). The review found little support from well-controlled studies in healthy, well-nourished people for the usual reasons to take glutamine: immune support, more glycogen storage, or an anti-catabolic effect.
Gut symptoms (supplement claim)
The gut is one of the main organs that handle glutamine, which is the basis for “gut health” marketing. The best controlled human evidence is narrow. A double-blind trial in adults who developed diarrhea-predominant irritable bowel syndrome (IBS) with increased intestinal permeability after a gut infection compared 5 g three times daily with placebo for 8 weeks (Zhou et al., Gut 2019):
- Response (a drop of at least 50 points on the IBS severity score): 79.6% on glutamine vs 5.8% on placebo, among 106 completers.
- Stool frequency, stool form and a urine test of gut permeability also improved.
- Adverse events were low and similar in the two groups.
The authors called for larger trials to confirm the result. It applies to this specific post-infectious IBS group and does not establish benefits for general digestive health.
Critical illness and burns
Glutamine was long added to nutrition for critically ill patients. Two large trials changed that view:
| Trial | Population | Glutamine arm | Main result |
|---|---|---|---|
| REDOXS (Heyland et al., NEJM 2013) | 1223 ICU adults with multiorgan failure on ventilators | IV plus enteral glutamine, 2×2 factorial with antioxidants | 28-day mortality 32.4% vs 27.2% without glutamine (adjusted OR 1.28, 95% CI 1.00–1.64; p = 0.05); in-hospital and 6-month mortality significantly higher |
| RE-ENERGIZE (Heyland et al., NEJM 2022) | 1200 patients with severe burns | 0.5 g/kg/day enteral | No faster discharge (median 40 vs 38 days; HR 0.91, 95% CI 0.80–1.04); 6-month mortality 17.2% vs 16.2% |
Side effects and risks
In the Endari trials
Across the two placebo-controlled trials (187 patients on Endari, 111 on placebo, 48 weeks plus a 3-week taper), these adverse reactions occurred in more than 10% of patients on Endari (Endari label):
| Adverse reaction | Endari | Placebo |
|---|---|---|
| Constipation | 21% | 18% |
| Nausea | 19% | 14% |
| Headache | 18% | 15% |
| Abdominal pain | 17% | 16% |
| Cough | 16% | 14% |
| Pain in extremity | 13% | 7% |
| Back pain | 12% | 5% |
| Chest pain | 12% | 8% |
Five patients (2.7%) stopped Endari because of adverse reactions. Three patients on Endari died during the studies and none on placebo; none of the deaths were judged related to the drug. Serious adverse reactions were more frequent on placebo and were consistent with the underlying disease.
Ammonia and glutamate
Glutamine is broken down into glutamate and ammonia. The NutreStore label warned that these may rise in people with liver dysfunction and recommended routine monitoring of kidney and liver function in patients also receiving IV nutrition, especially with kidney or liver impairment (NutreStore label). The phase 3 Endari trial excluded patients with renal insufficiency or uncontrolled liver disease, so data in those groups are lacking.
Critically ill patients
The REDOXS trial found higher mortality with high-dose glutamine in ventilated ICU patients with multiorgan failure, and the RE-ENERGIZE burn trial found no benefit. Glutamine is not harmless in every setting.
Intake levels studied in healthy adults
No consistent pattern of adverse effects has been found in trials of oral glutamine in healthy adults, so no standard upper limit exists. A risk assessment by authors from the Council for Responsible Nutrition, a supplement-industry trade group, set an “observed safe level” of 14 g/day for supplemental glutamine. It noted that higher intakes had been tested without harm, but the data were too limited to be confident about long-term safety above that level (Shao and Hathcock, Regul Toxicol Pharmacol 2008). A separate review reported that single intakes of about 20–30 g appeared to be without ill effect, and one study in athletes found no harm at 28 g/day for 14 days (Gleeson, J Nutr 2008).
Pregnancy, breastfeeding and interactions
There are no human data on Endari in pregnancy or breastfeeding, and no animal reproduction studies were done. No formal drug interaction studies have been done (Endari label).
Legal status
- United States. Endari and its generics are prescription drugs. L-glutamine is also widely sold in dietary supplements (Shao and Hathcock, Regul Toxicol Pharmacol 2008), which are not reviewed by FDA for efficacy. It is not a controlled substance.
- European Union. The Xyndari application for sickle cell disease was withdrawn before a final decision, so it was not authorized.
- Sport. Glutamine is not named on the WADA 2026 Prohibited List.
Related library pages: taurine (assessed alongside glutamine in the same safety review), HMB and creatine monohydrate.
Key takeaways
- Two different products. Prescription Endari is FDA-approved for sickle cell disease; supplement glutamine is sold for muscle, recovery, immune and gut claims that FDA has not evaluated.
- The approval rests on one trial. In sickle cell disease, glutamine reduced the median number of crises from 4 to 3 over 48 weeks and cut acute chest syndrome, but EMA judged the same data insufficient because of dropouts and missing-data handling.
- No muscle-building effect shown. In resistance-trained young adults and in a meta-analysis of athletes, glutamine did not improve strength, lean mass or body composition.
- Immune and gut claims are thin. Supplements keep plasma glutamine up after exercise but do not prevent immune changes; one trial showed a large benefit only in post-infectious IBS.
- Generally well tolerated orally, but not risk-free. About 14 g/day is the observed safe level in healthy adults; high doses increased mortality in critically ill ICU patients, and people with liver or kidney disease were not studied.
Sources
- Emmaus Medical. Endari (L-glutamine oral powder), prescribing information. DailyMed; Drugs@FDA, NDA 208587.
- Emmaus Medical. NutreStore (L-glutamine powder for oral solution), prescribing information, NDA 021667/S-007, revised 10/2020. FDA; Drugs@FDA, NDA 021667.
- Food and Drug Administration. L-glutamine oral powder, ANDA 215647, approved July 8, 2024. Drugs@FDA.
- European Medicines Agency. Xyndari: withdrawal of application for marketing authorisation (EMA/521995/2019). EMA.
- Niihara Y, Miller ST, Kanter J, et al. A phase 3 trial of l-glutamine in sickle cell disease. N Engl J Med. 2018;379(3):226–235. PubMed.
- Cieri-Hutcherson NE, Hutcherson TC, Conway-Habes EE, et al. Systematic review of l-glutamine for prevention of vaso-occlusive pain crisis in patients with sickle cell disease. Pharmacotherapy. 2019;39(11):1095–1104. PubMed.
- Cruzat V, Macedo Rogero M, Noel Keane K, et al. Glutamine: metabolism and immune function, supplementation and clinical translation. Nutrients. 2018;10(11):1564. PubMed.
- Candow DG, Chilibeck PD, Burke DG, et al. Effect of glutamine supplementation combined with resistance training in young adults. Eur J Appl Physiol. 2001;86(2):142–149. PubMed.
- Ramezani Ahmadi A, Rayyani E, Bahreini M, et al. The effect of glutamine supplementation on athletic performance, body composition, and immune function: a systematic review and a meta-analysis of clinical trials. Clin Nutr. 2019;38(3):1076–1091. PubMed.
- Legault Z, Bagnall N, Kimmerly DS. The influence of oral L-glutamine supplementation on muscle strength recovery and soreness following unilateral knee extension eccentric exercise. Int J Sport Nutr Exerc Metab. 2015;25(5):417–426. PubMed.
- Gleeson M. Dosing and efficacy of glutamine supplementation in human exercise and sport training. J Nutr. 2008;138(10):2045S–2049S. PubMed.
- Zhou Q, Verne ML, Fields JZ, et al. Randomised placebo-controlled trial of dietary glutamine supplements for postinfectious irritable bowel syndrome. Gut. 2019;68(6):996–1002. PubMed.
- Heyland D, Muscedere J, Wischmeyer PE, et al. A randomized trial of glutamine and antioxidants in critically ill patients. N Engl J Med. 2013;368(16):1489–1497. PubMed.
- Heyland DK, Wibbenmeyer L, Pollack J, et al. A randomized trial of enteral glutamine for treatment of burn injuries. N Engl J Med. 2022;387(11):1001–1010. PubMed.
- Shao A, Hathcock JN. Risk assessment for the amino acids taurine, L-glutamine and L-arginine. Regul Toxicol Pharmacol. 2008;50(3):376–399. PubMed.
- World Anti-Doping Agency. The 2026 Prohibited List. WADA 2026 Prohibited List.