Glutamine is an amino acid, one of the building blocks of protein. It is the most abundant free amino acid in blood and muscle. It is the amide of glutamic acid (glutamic acid with an extra nitrogen group), which gives it two amino groups. It is a different amino acid from glutamic acid (glutamate), which has its own glutamic acid page.
The WHO and the European Food Safety Authority list glutamine as conditionally indispensable. That means the body usually makes enough but can fall short in severe illness or injury. The US National Academies list it the same way in their table of amino acids, although the text of their glutamine section calls it dispensable.
No daily requirement is set, and food does not have to supply it.
Beyond building protein, glutamine is the body’s main way of moving nitrogen between organs. Muscle, lung, liver, brain and fat tissue make it, and gut lining cells and immune cells burn it as fuel.
Its nitrogen goes into the building blocks of DNA and RNA and into amino sugars, and it gives glutamate for making glutathione. In the kidney, it supplies the ammonia that carries acid out in urine. In the brain, it is the raw material that nerve cells recycle into glutamate and GABA.
Here is what most readers do not know. Your body makes far more glutamine than you eat.
Estimates of its own output are 40 to 80 g a day in one review. The National Academies report gives 60 to 100 g a day. Food gives about 6.8 g a day in a large US study of women, an estimate, because USDA does not measure glutamine.
Gut and liver cells also keep more than half of the glutamine you swallow before it reaches the blood. And glutamine is sold as fuel for the immune system, yet the largest trials in intensive care found no benefit, and one found more deaths. One oral glutamine powder is approved in the United States as a medicine, for sickle cell disease.
Health benefits of glutamine
Almost everything tested in people is a supplement, not food. It is glutamine powder or capsules by mouth, or glutamine given by feeding tube or into a vein in hospital. It comes either as free L-glutamine or as alanyl-glutamine, a pair of two amino acids (see the forms section).
The best-supported findings are findings of no benefit. Pooled analyses of trials in intensive care and of trials in premature babies found no effect on deaths. In the REDOXS trial, early glutamine was linked to higher mortality in patients with multiple organ failure.
The trial result behind a recent drug approval is in sickle cell disease. The US FDA approved L-glutamine for it in 2017. The European Medicines Agency’s review in 2019 concluded that the main trial did not show the medicine worked. Small trials of gut symptoms, exercise and diabetes point in different directions.
The EU Register of health claims lists 22 entries for glutamine, for muscle, gut, immune and brain effects, and every one is non-authorized. None of the findings below is strong evidence of a benefit. Here is what 18 studies found, strongest evidence first, including the trials that found nothing.
Enteral glutamine did not change hospital deaths in critical illness
This 2024 meta-analysis (a study that pools earlier trials) covered 18 randomized trials in 2,552 critically ill adults. They got glutamine by feeding tube or by mouth (enteral), against none or placebo (a dummy). Trials that gave it only or partly into a vein (parenteral) were left out. Hospital deaths did not change (odds ratio 1.05), and trial sequential analysis confirmed the mortality result. Intensive care stay (mean difference -0.07 days) and infections (odds ratio 0.90) did not change either, while hospital stay was 2.85 days shorter. The authors, who declared no competing interests, say the data do not support routine enteral glutamine in critical illness.
Glutamine did not cut deaths or infections in preterm babies
This Cochrane review (Cochrane is a group known for careful reviews of trials) covered 12 trials in 2,877 preterm infants. Six gave glutamine by feeding tube and six by vein, against no glutamine, at any time from birth to discharge. The risk of death was 0.97 times that without glutamine, and necrotizing enterocolitis (a serious bowel disease) did not change either. Three trials that followed children to 18 to 24 months and beyond found no effects on development. The reviewers rated the trials as generally good quality and found no evidence of important benefits. This is the latest version of the review, from April 2016, and it is not withdrawn.
In organ failure, glutamine went with more deaths: 32.4% against 27.2%
This blinded 2-by-2 trial enrolled 1,223 ventilated patients with multiple organ failure in 40 intensive care units. The units were in Canada, the United States and Europe. Patients received glutamine, antioxidants, both, or placebo, starting within 24 hours of admission and given both into a vein and by feeding tube. The 28-day difference had an adjusted odds ratio of 1.28, and in-hospital and 6-month deaths were clearly higher with glutamine. Glutamine had no effect on organ failure or infections, and antioxidants had no effect on 28-day mortality (30.8% against 28.8%). A later analysis of the same trial found the greatest potential for harm in patients with kidney dysfunction at entry. Funded by the Canadian Institutes of Health Research.
In 1,200 burn patients, tube or oral glutamine did not speed discharge
This double-blind, placebo-controlled trial gave glutamine to 596 adults with severe burns and placebo to 604. The dose was 0.5 g per kg of body weight a day, by feeding tube or by mouth, started within 72 hours of admission. It continued until 7 days after the last skin graft, discharge from the acute care unit, or 3 months. Mean burn size was 33% of body surface. Median time to discharge alive was 40 days with glutamine and 38 with placebo (subdistribution hazard ratio 0.91), a gap that could be chance. Six-month mortality was 17.2% against 16.2%, and serious adverse events did not differ substantially. Funded by the U.S. Department of Defense and the Canadian Institutes of Health Research.
Show 14 more studies
Cochrane review of 53 trials: glutamine cut infections, not clearly deaths
The 53 trials enrolled 4,671 adults in intensive care or after major elective surgery. They compared glutamine by vein or gut with none or placebo. In 33 trials, infections fell to 0.79 times the risk. Short-term mortality did not clearly change (risk ratio 0.89, 36 trials), nor did mortality after more than six months (1.00). Hospital stay was 3.46 days shorter and intensive care stay slightly longer. The authors rated the evidence low to moderate because of bias, suspected publication bias and varied results. The search ended in May 2013, and this is the latest version.
After surgery, alanyl-glutamine drips did not change hospital deaths
This double-blind multicenter trial enrolled 150 surgical intensive care patients on parenteral nutrition (feeding by vein). They had had gastrointestinal, vascular or cardiac surgery, with no major kidney or liver failure or shock at entry. Everyone received 1.5 g per kg a day of amino acids. In the glutamine group, the dipeptide alanyl-glutamine (0.5 g per kg a day) replaced part of them. Hospital deaths were 14.7% with it and 17.3% without, and six-month mortality was 31.4% against 29.7%. Bloodstream infections were 9.6 against 8.4 per 1,000 hospital days. The authors found the supplement safe but without effect on clinical outcomes.
In sickle cell disease, L-glutamine cut pain crises to 3.0 from 4.0
This placebo-controlled, double-blind phase 3 trial ran 48 weeks in 230 people with sickle cell anemia or sickle beta-zero thalassemia. 152 took L-glutamine at 0.3 g per kg of body weight twice a day by mouth, and 78 took placebo. They were aged 5 to 58, all with 2 or more crises in the year before, and two thirds also took hydroxyurea. The crisis figures are medians, and hospitalizations were fewer too (median 2.0 against 3.0). Low-grade nausea, chest pain not from the heart, fatigue and muscle or bone pain were more common with glutamine. Funded by Emmaus Medical, the maker of the approved product, this single trial supported the 2017 US approval.
In athletes, glutamine did not change immunity, fitness or body composition
The review covered 47 studies and pooled 25 clinical trials in adults over 18, searched to January 2017, with various glutamine doses and forms. Glutamine was linked to a small weight loss (weighted mean difference -1.36) and to lower neutrophil counts at doses above 200 mg per kg. Neutrophils are a type of white blood cell. The dipeptide form gave higher blood glucose after exercise (0.51 mmol/L). The authors say the effect on neutrophils may depend on form and dose, and they found no link with the other outcomes.
In cancer, glutamine cut severe mouth sores, not overall cases
This meta-analysis pooled 15 trials in 988 people with cancer having chemotherapy, radiotherapy or both, and looked at oral mucositis (painful mouth sores). Severe mucositis fell (risk ratio 0.41), and glutamine reduced severity (standardized mean difference -0.73) but not the overall incidence (0.94). It also cut the use of opioid painkillers (risk ratio 0.84), feeding tubes (0.46), hospitalization (0.39) and treatment interruption (0.49). Searches ran to September 2020, and the results conflict with the meta-analysis in head and neck cancer below.
In head and neck cancer, glutamine did not prevent mouth sores
This meta-analysis pooled 6 trials in 441 people with head and neck cancer, having radiotherapy alone or with chemotherapy. Oral glutamine did not lower the incidence of oral mucositis (risk ratio 0.98). Nor did it clearly lower moderate-to-severe mucositis (0.81) or severe mucositis (0.45). Opioid use was slightly lower (0.84), which the authors call a marginal effect. They say better and larger trials are needed.
In post-infection IBS, glutamine cut symptoms far more than placebo
This randomized, double-blind 8-week trial enrolled 106 adults who developed irritable bowel syndrome (IBS) with diarrhea and raised gut permeability after an infection. They took glutamine at 5 g three times a day (15 g a day), and 54 on glutamine and 52 on placebo completed it. A 50-point drop in symptom score came in 79.6% on glutamine against 5.8% on placebo. Stool frequency, stool form and a lactulose-mannitol permeability test also improved, and the raised permeability normalized only in the glutamine group. Adverse events were low and similar, and no competing interests were declared. The effect is very large for a trial of this kind, and the authors call for larger trials to confirm it.
In 53 children, L-glutamine cut pain crises to 1.00 from 1.65
This double-blind, placebo-controlled trial enrolled children and teenagers with sickle cell anemia already on hydroxyurea (about 20 mg per kg a day). Over 6 months, 27 got added L-glutamine and 26 got placebo. Acute chest syndrome episodes were 0.19 against 0.77, hospitalizations fell by 40%, and hemoglobin rose more (0.78 against 0.32 g/dL). No serious adverse events occurred, and the abstract does not give the glutamine dose. The trial is small and short, and the authors say larger trials are needed to confirm it. No conflict of interest was declared.
In 10 men running in heat, glutamine lowered a gut leak marker
In this randomized crossover trial, the men ran 60 minutes in 30°C heat, with a placebo run and three glutamine runs. Glutamine doses were 0.25, 0.5 and 0.9 g per kg of fat-free mass, taken 2 hours before. The lactulose-to-rhamnose ratio in blood was lower than on placebo by 0.023, 0.019 and 0.034, most at the highest dose. Stomach and bowel symptoms were low and did not differ. For a man with 60 kg of fat-free mass, those doses are 15, 30 and 54 g (our arithmetic). The authors say it remains unclear whether this lowers symptoms.
In 10 men in 40°C heat, glutamine made gut permeability worse
In this randomized crossover trial, the men took about 20 g of glutamine (0.3 g per kg of fat-free mass) or placebo. They took it one hour before running to exhaustion. Permeability (lactulose-to-rhamnose ratio) was higher after glutamine, 0.043 against 0.034. A marker of gut lining injury and a marker of bacteria crossing the gut wall did not differ. Time to exhaustion was about 22 minutes in both trials. The authors say the results do not support glutamine to prevent exertional heat stroke.
In 31 young adults, glutamine added nothing to strength or lean mass
This double-blind trial gave young adults glutamine (17 people) or a maltodextrin placebo (14 people) by mouth for 6 weeks. The glutamine dose was 0.9 g per kg of lean mass a day, with total-body resistance training. Both groups raised their squat by about 30% and bench press by about 14%. Lean tissue mass rose 2% with glutamine and 1.7% with placebo, and a marker of muscle breakdown rose in both. The authors conclude glutamine has no clear effect on performance, body composition or muscle breakdown in healthy young adults.
After exercise, 81% on glutamine reported no infection, against 49% on placebo
The 151 athletes in different sports drank glutamine or placebo drinks right after exercise and 2 hours later (72 on glutamine, 79 on placebo). They then filled in a questionnaire about infections in the next 7 days. The infections were self-reported, and the abstract does not give the dose. Later controlled work did not confirm that glutamine prevents the dip in immune function after hard exercise (see How glutamine works).
In diabetes, glutamine lowered glucose and HbA1c a little
This double-blind trial gave 66 adults with type 2 diabetes glutamine or placebo for 6 weeks. The dose was 10 g three times a day (30 g a day). In the 53 who finished, fasting glucose and HbA1c (a long-term blood sugar marker) fell a little more with glutamine. Body fat mass and waist circumference also fell more with glutamine. Fasting insulin, cholesterol, triglycerides and C-reactive protein did not differ. A later trial from the same group (33 patients per group) found no change in glucose or insulin after a meal.
Low blood glutamate, not glutamine, predicted death in medical inpatients
This secondary analysis of the EFFORT randomized trial of nutritional support measured plasma glutamine and glutamate in 234 medical inpatients at nutritional risk. Low glutamate went with 2.35 times the risk of death within 30 days, after adjustment. It stayed linked to mortality for up to 5 years. Plasma glutamine itself was not linked to short- or long-term death, which differs from studies in intensive care. Neither measure was related to how well the nutritional support worked.
Foods high in glutamine
Glutamine is in every protein, and USDA does not report it. The usual lab method breaks glutamine down to glutamic acid, so food tables count the two together as glutamic acid. That is why our food ranking has no glutamine list.
The numbers below come from a Harvard study that calculated glutamine from protein sequence data. By those estimates, glutamine makes up from 1% of the protein in kidney beans to 33% of the protein in whole grain bread. It runs from 0.01 g per 100 g in apple juice to 9.49 g per 100 g in wheat germ.
Per 100 g, beef leads the six foods the study lists in full, because it holds the most protein. But grains carry the largest share: 16.2% of the protein in corn and 11.1% in white rice, against 4.8% in beef and 4.4% in egg.
A separate lab analysis of plant foods found glutamine to be the most abundant amino acid in wheat flour, white rice and pistachios. It was the second most abundant in corn, peanuts, potatoes and soybeans.
Almost all the amino acids in these foods are bound in protein. Free amino acids were 3.1% or less of the total in corn, peanuts, pistachios, soybeans, wheat flour and white rice, but 34.4% in potatoes.
| Food | Glutamine per 100 g of food | Share of the food’s protein | Source |
|---|---|---|---|
| Wheat germ | 9.49 g | not stated | 1 |
| Beef | 1.23 g | 4.8% | 1 |
| Tofu (soy) | 0.60 g | 9.1% | 1 |
| Egg | 0.56 g | 4.4% | 1 |
| Corn | 0.41 g | 16.2% | 1 |
| White rice | 0.30 g | 11.1% | 1 |
| Skim milk | 0.28 g | 8.1% | 1 |
No daily amount is set, so we cannot say what share of a requirement a serving gives. For scale, the women in the Nurses’ Health Study ate an estimated 6.84 g of glutamine a day.
By our arithmetic, 100 g of beef (1.23 g) is about 18% of that, and 100 g of tofu about 9%. One 50 g egg (0.28 g) is about 4%. Standard tube-feeding formulas hold 2 to 4 g per liter, a Swedish intensive care specialist writes. That is not enough to bring low blood glutamine back to normal.
Sources
- Lenders CM, Liu S, Wilmore DW, et al. Evaluation of a novel food composition database that includes glutamine and other amino acids derived from gene sequencing data. Eur J Clin Nutr. 2009.
- Hou Y, He W, Hu S, et al. Composition of polyamines and amino acids in plant-source foods for human consumption. Amino Acids. 2019.
- WHO/FAO/UNU Expert Consultation. Protein and amino acid requirements in human nutrition. WHO Technical Report Series 935. World Health Organization. 2007.
- Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids. National Academies Press. 2005.
- Wernerman J. Glutamine supplementation. Ann Intensive Care. 2011.
How glutamine works
Most of what follows comes from reviews, tracer studies in small groups of people and lab work, not from trials of pills.
Four ideas cover it. Muscle makes glutamine and shares it with the gut, immune cells and kidney, and the gut keeps over half of what you eat. In the brain it carries nitrogen between cells, and in sickle cell disease it may protect red cells. Then comes what has been seen in people.
Muscle makes it and shares it
A 70 kg adult holds roughly 70 to 80 g of glutamine. Blood plasma carries 500 to 800 µmol/L (micromoles per liter) of it, about 20% of the free amino acids there. Skeletal muscle holds about 80% of the body’s supply.
In the post-absorptive state (after a meal has been absorbed), glutamine and alanine make up 48% and 32% of the amino acids that muscle releases. Glutamine has two amino groups, so it is the main way muscle sends nitrogen to other organs.
Gut cells and immune cells burn it as fuel. In the kidney, it supplies the ammonia that combines with acid to be excreted. EFSA adds that glutamine is used to make the nucleotides in DNA and RNA.
Where glutamine is made and used. Not to scale; the share figures come from reviews.
In severe illness the balance tips. The WHO notes that plasma glutamine falls in critical illness. It adds that muscle glutamine fell by more than half in patients with bacteremia (bacteria in the blood). A review of intensive care says use rises while muscle’s ability to make more is impaired, so the whole body runs short.
Another review puts the average drop in muscle glutamine at about 80%. It puts the fall in plasma at 500 to 800 down to 300 to 400 µmol/L. Yet immune cells still multiplied in the lab at about 400 µmol/L.
A low plasma level is an independent risk factor for death in intensive care, according to a Swedish specialist. Whether giving glutamine fixes this is what the trials above tested, and it did not.
The gut keeps more than half of what you eat
Glutamine you swallow does not all reach the blood. In 14 healthy adults given labeled amino acids by feeding tube, the gut and liver kept 54% of the glutamine on the first pass. They kept 88% of the glutamate. In five preterm babies, first-pass uptake was 73% and 57% on two study days, and its carbon was an important fuel.
In five men, the share kept on the first pass was 74% for a trace dose. It fell to 53% when the tracer came with a large glutamine load. That load also doubled blood glutamine, from 630 to 1,297 µmol/L. It lowered the body’s own production from 156 to 93 µmol per kg per hour.
How much of a tube-fed amino acid the gut and liver keep on the first pass. Drawn to scale.
Higher doses do not raise blood levels in proportion. After a single dose of 0.1 g per kg, the FDA label says, blood glutamine peaked at about 1,028 µmol/L within roughly 30 minutes. Higher doses suggested a saturable absorption process (absorption that tops out).
A study in sickle cell patients and healthy adults confirmed that peaks did not rise in proportion to dose. Nothing accumulated on twice-daily dosing, and food did not change clearance.
In the brain it carries nitrogen between cells
Nerve cells cannot make the neurotransmitters glutamate and GABA from glucose on their own. After they release them, support cells called astrocytes take them up, turn them into glutamine and send it back. The cycle also moves nitrogen, as ammonia, between the two cells.
Glutamine is not the signal itself; for glutamate as a brain signal, see the glutamic acid page. The need for the supply shows in a very rare disease. Two newborns with congenital glutamine synthetase deficiency had almost no glutamine in blood, urine and spinal fluid, had severe brain malformations, and died. A 2016 review counted only three such patients known.
The glutamate/GABA-glutamine cycle between nerve cells and astrocytes. Not to scale.
It may protect sickled red cells
Red cells in sickle cell disease are prone to oxidative damage. The FDA label says L-glutamine may improve the cells’ NAD redox balance by raising the supply of reduced glutathione, an antioxidant. It adds that its mechanism is not fully understood.
A small lab study tested red cells from 5 patients on 30 g a day for at least 4 weeks. They stuck to vessel-wall cells about half as much as cells from untreated patients (0.97 against 1.91, in the paper’s units).
The proposed way L-glutamine may act in sickle cell disease. A proposed pathway, not proven.
Regulators weighed the trial differently. For the phase 3 trial, the FDA label reports a median of 3 crises against 4, and hospitalizations of 2 against 3. Acute chest syndrome affected 8.6% against 23.1%.
The European Medicines Agency reviewed the same product in 2019. It considered that the main study did not show it reduced crises or hospital visits. Its reasons: many patients dropped out, more of them on glutamine, and the way their data were handled was not appropriate. It also had concerns about the supporting study of 70 patients, in which more people on glutamine than on placebo also took hydroxyurea.
The company withdrew its application on September 18, 2019, giving a change in marketing strategy as its reason.
A 2018 review in Blood says there are few published studies of L-glutamine for the disease and many unanswered questions. A 2019 systematic review found only three eligible studies, of which one randomized trial gave strong evidence.
What has been seen in people
The clearest human results are negative. In intensive care, 18 pooled trials of enteral glutamine found no change in hospital deaths. One large trial found higher mortality in patients with multiple organ failure, and in severe burns 1,200 patients gained nothing in time to discharge. In premature babies, 12 trials found no benefit.
In sickle cell disease, one large trial found fewer pain crises, and regulators disagreed about it. In post-infection IBS with diarrhea, one trial reported a large benefit that needs confirming. In runners in heat, the results went both ways.
Meta-analyses in athletes found no effect on performance, immune markers or body composition. A review of dosing looked at the reasons for taking glutamine: immunity, glycogen and anti-catabolic effects (less muscle breakdown). It says they have received little support from well-controlled studies in healthy, well-nourished people.
Two small Crohn’s trials (42 patients in all) and trials in short bowel syndrome, mostly with growth hormone, are too small to settle anything. In type 2 diabetes, one 6-week trial found small improvements in fasting glucose, and a later one found no change after a meal. We found no trial showing that more glutamine from food improves any health outcome.
Sources
- WHO/FAO/UNU Expert Consultation. Protein and amino acid requirements in human nutrition. WHO Technical Report Series 935. World Health Organization. 2007.
- Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids. National Academies Press. 2005.
- EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Scientific opinion on dietary reference values for protein. EFSA Journal. 2012;10(2):2557. Version published February 5, 2015.
- Cruzat V, Macedo Rogero M, Noel Keane K, et al. Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation. Nutrients. 2018.
- Biolo G, Zorat F, Antonione R, et al. Muscle glutamine depletion in the intensive care unit. Int J Biochem Cell Biol. 2005.
- Wernerman J. Glutamine supplementation. Ann Intensive Care. 2011.
- Matthews DE, Marano MA, Campbell RG. Splanchnic bed utilization of glutamine and glutamic acid in humans. Am J Physiol. 1993.
- Hankard RG, Darmaun D, Sager BK, et al. Response of glutamine metabolism to exogenous glutamine in humans. Am J Physiol. 1995.
- van der Schoor SR, Schierbeek H, Bet PM, et al. Majority of dietary glutamine is utilized in first pass in preterm infants. Pediatr Res. 2010.
- Sadaf A, Dong M, Pfeiffer A, et al. A Population Pharmacokinetic Analysis of L-Glutamine Exposure in Patients with Sickle Cell Disease: Evaluation of Dose and Food Effects. Clin Pharmacokinet. 2024.
- Emmaus Medical. ENDARI (L-glutamine) oral powder: prescribing information. US National Library of Medicine, DailyMed. Label version of June 27, 2025.
- Bak LK, Schousboe A, Waagepetersen HS. The glutamate/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer. J Neurochem. 2006.
- Häberle J, Görg B, Rutsch F, et al. Congenital glutamine deficiency with glutamine synthetase mutations. N Engl J Med. 2005.
- Spodenkiewicz M, Diez-Fernandez C, Rüfenacht V, et al. Minireview on Glutamine Synthetase Deficiency, an Ultra-Rare Inborn Error of Amino Acid Biosynthesis. Biology (Basel). 2016.
- Niihara Y, Matsui NM, Shen YM, et al. L-glutamine therapy reduces endothelial adhesion of sickle red blood cells to human umbilical vein endothelial cells. BMC Blood Disord. 2005.
- Quinn CT. l-Glutamine for sickle cell anemia: more questions than answers. Blood. 2018.
- European Medicines Agency. Withdrawal of application for the marketing authorisation of Xyndari (glutamine). EMA/521995/2019. October 18, 2019.
- Gleeson M. Dosing and efficacy of glutamine supplementation in human exercise and sport training. J Nutr. 2008.
- 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.
- Akobeng AK, Elawad M, Gordon M. Glutamine for induction of remission in Crohn’s disease. Cochrane Database Syst Rev. 2016.
- Wales PW, Nasr A, de Silva N, et al. Human growth hormone and glutamine for patients with short bowel syndrome. Cochrane Database Syst Rev. 2010.
- Mansour A, Mohajeri-Tehrani MR, Qorbani M, et al. Postprandial glycemia and insulin secretion following glutamine administration: A randomized controlled trial. Int J Vitam Nutr Res. 2020.
How much glutamine do you need?
There is no daily amount of glutamine to aim for. The body makes it, and neither the WHO nor the US National Academies sets a requirement. The National Academies say the amounts needed for conditionally indispensable amino acids have not been determined and probably vary greatly with the condition. The site has no Daily Value for glutamine, because neither the FDA nor the EU has set one.
Food supplies a few grams a day. In the Nurses’ Health Study, 70,356 women aged 38 to 63 in 1984 had an estimated mean glutamine intake of 6.84 g a day. The spread (standard deviation) was 2.19. It was calculated from their food questionnaires with protein sequence data, because USDA tables lack glutamine.
The body’s own output is much larger: 40 to 80 g a day by one review and 60 to 100 g by the National Academies. That is roughly 6 to 15 times the dietary intake (our arithmetic).
Babies start life on a milk that is rich in it. In 16 women, free glutamine in human milk rose about 20 times from colostrum (the first milk) to 3 months. With glutamic acid, it made up more than half of the free amino acids. We found no source that gives a glutamine requirement for children, pregnancy or breastfeeding.
Glutamine deficiency: signs and who is at risk
A shortfall caused by diet alone is not known. The WHO says that when total nitrogen intake is low, making the dispensable amino acids may become limited. It names glycine and glutamine as the likely limits. That is a protein shortage, and the fix is enough total protein.
The clearest at-risk group is people under severe catabolic stress (heavy tissue breakdown), such as critical illness, serious burns or sepsis. The National Academies describe adults in this state whose tissues cannot make enough glutamine. For them, a dietary source is needed to keep nitrogen in balance. They add that glutamine and arginine can become indispensable when the gut’s metabolism fails.
Blood levels fall and muscle stores fall further, and a low plasma level goes with a worse outcome in intensive care. As the trials on this page show, giving glutamine has not improved outcomes in these patients. So a low level alone is not a reason to supplement.
Two rarer situations are on record. EFSA names premature babies among those who can run short of conditionally indispensable amino acids, yet 12 trials found no important benefit from adding glutamine.
And a few newborns have been born unable to make glutamine, because of a defect in glutamine synthetase. They had low glutamine and high ammonia in the blood. A 2016 review counted three known patients, all with severe epilepsy from birth.
Sources
- WHO/FAO/UNU Expert Consultation. Protein and amino acid requirements in human nutrition. WHO Technical Report Series 935. World Health Organization. 2007.
- Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids. National Academies Press. 2005.
- EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Scientific opinion on dietary reference values for protein. EFSA Journal. 2012;10(2):2557. Version published February 5, 2015.
- Lenders CM, Liu S, Wilmore DW, et al. Evaluation of a novel food composition database that includes glutamine and other amino acids derived from gene sequencing data. Eur J Clin Nutr. 2009.
- Agostoni C, Carratù B, Boniglia C, et al. Free glutamine and glutamic acid increase in human milk through a three-month lactation period. J Pediatr Gastroenterol Nutr. 2000.
- Cruzat V, Macedo Rogero M, Noel Keane K, et al. Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation. Nutrients. 2018.
- Biolo G, Zorat F, Antonione R, et al. Muscle glutamine depletion in the intensive care unit. Int J Biochem Cell Biol. 2005.
- Wernerman J. Glutamine supplementation. Ann Intensive Care. 2011.
- Häberle J, Görg B, Rutsch F, et al. Congenital glutamine deficiency with glutamine synthetase mutations. N Engl J Med. 2005.
- Spodenkiewicz M, Diez-Fernandez C, Rüfenacht V, et al. Minireview on Glutamine Synthetase Deficiency, an Ultra-Rare Inborn Error of Amino Acid Biosynthesis. Biology (Basel). 2016.
- Moe-Byrne T, Brown JV, McGuire W. Glutamine supplementation to prevent morbidity and mortality in preterm infants. Cochrane Database Syst Rev. 2016.
Forms of glutamine: absorption and effects
Glutamine comes in a few packages. It is bound in food protein, sold as free L-glutamine powder or capsules, or sold as the dipeptide alanyl-glutamine (glutamine joined to alanine). It is also in tube feeds and nutrition drips for hospital patients. In the blood it ends up the same, free L-glutamine. The forms differ in stability, and in how fast and how high they raise blood glutamine.
The honest bottom line: no form has been shown to work better than another for a health outcome. Free glutamine is unstable in water, a Swedish intensive care specialist writes, which is why standard nutrition drips contain none.
A review adds that the dipeptides are stable during sterilization and storage. They are also far more soluble: 154 and 568 g per liter of water, against 36 for free glutamine. The review says the alanine dipeptide tends to give a higher peak than free glutamine, citing animal and human work.
But we found no randomized trial that compared free glutamine, alanyl-glutamine and glutamine peptides for any health outcome. We also found no human trial of N-acetyl-L-glutamine or of other forms sold online. The sickle cell trials used free L-glutamine, and the intensive care and surgery trials used both free glutamine and the dipeptide.
| Form | What it is | What studies show | Source |
|---|---|---|---|
| Protein-bound glutamine | Part of the protein chain in meat, dairy and grains; about 5% to 6% of bound amino acids | Among six foods the share of protein ranges from 4.4% in egg to 16.2% in corn. In 13 bodybuilders, 1.5 g per kg a day of hydrolyzed whey isolate or casein for 10 weeks left blood glutamine unchanged. In 30 randomized Crohn’s patients in remission, 0.5 g per kg of ideal body weight a day of glutamine or of whey protein for 2 months improved gut permeability in both groups equally. | 1, 2, 3, 4 |
| Free L-glutamine powder | White crystalline powder; the prescription product comes in 5 g packets | After 0.1 g per kg, blood glutamine peaked at about 1,028 µmol/L in 30 minutes and the half-life after a vein bolus was about 1 hour. Peaks rose less than the dose, nothing built up on twice-daily dosing, and food did not change clearance. The label says to mix each dose into a drink or soft food just before taking it. | 5, 6 |
| Alanyl-glutamine dipeptide | Glutamine joined to alanine; stable in water and used in hospital nutrition | A 20 g oral bolus raised blood glutamine by 794 µmol/L and the same amount in portions by 398 (cards below). By vein it gave higher blood glutamine than by tube at a higher dose, with no clear difference in antioxidant or gut markers, and in surgery patients 0.5 g per kg a day did not change outcomes. | 7, 8, 9, 10 |
| Glutamine peptides and glutamine-enriched products | Protein pieces from hydrolyzed wheat or milk protein, or foods with glutamine added | We found no human trial that tests them for a health outcome. The EU Register lists claims for glutamine and glutamine peptide, and all are non-authorized. | 12 |
| Tube feeds and nutrition drips | Standard enteral formulas hold some glutamine; standard parenteral formulas hold none | Standard enteral formula holds 2 to 4 g per liter, not enough to normalize blood glutamine. In the EU, glutamine is an active substance in several parenteral nutrition medicines. | 7, 11 |
| Glutamic acid and MSG | A different amino acid that the body converts to and from glutamine | Not a form of glutamine, and trials of one say nothing about the other. The National Academies name high blood ammonia and high glutamic acid as the potential hazards of glutamine consumption. See the glutamic acid page. | 13 |
Here are the two studies that compare how glutamine given as the dipeptide behaves in people, one by dosing pattern and one by route.
A 20 g alanyl-glutamine bolus gave a higher peak than split doses
In 8 healthy adults, oral L-alanyl-glutamine was given as one bolus or in intermittent doses. The peak rise was 794 against 398 µmol/L, but the total exposure over time did not differ. The acid-suppressing drug omeprazole did not change the response in 4 of the volunteers, and 8 patients with dengue fever responded like healthy people. Alanine rose in parallel.
Drip alanyl-glutamine beat tube feeding for blood glutamine, at a higher dose
This double-blind pilot trial in 44 tube-fed intensive care patients gave alanyl-glutamine into a vein or by tube, against an isonitrogenous control (same nitrogen). The goal was 0.5 g per kg a day, but the tube group actually received 0.32. Blood glutamine reached 565 µmol/L with the vein route against 411 with the tube. After 9 days there were no differences between groups in antioxidant markers, T-cell numbers, gut permeability or nitrogen balance. Twelve patients stopped the study early, and the authors call it a pilot.
Sources
- Cruzat V, Macedo Rogero M, Noel Keane K, et al. Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation. Nutrients. 2018.
- Lenders CM, Liu S, Wilmore DW, et al. Evaluation of a novel food composition database that includes glutamine and other amino acids derived from gene sequencing data. Eur J Clin Nutr. 2009.
- Cribb PJ, Williams AD, Carey MF, et al. The effect of whey isolate and resistance training on strength, body composition, and plasma glutamine. Int J Sport Nutr Exerc Metab. 2006.
- Benjamin J, Makharia G, Ahuja V, et al. Glutamine and whey protein improve intestinal permeability and morphology in patients with Crohn’s disease: a randomized controlled trial. Dig Dis Sci. 2012.
- Emmaus Medical. ENDARI (L-glutamine) oral powder: prescribing information. US National Library of Medicine, DailyMed. Label version of June 27, 2025.
- Sadaf A, Dong M, Pfeiffer A, et al. A Population Pharmacokinetic Analysis of L-Glutamine Exposure in Patients with Sickle Cell Disease: Evaluation of Dose and Food Effects. Clin Pharmacokinet. 2024.
- Wernerman J. Glutamine supplementation. Ann Intensive Care. 2011.
- Klassen P, Mazariegos M, Solomons NW, et al. The pharmacokinetic responses of humans to 20 g of alanyl-glutamine dipeptide differ with the dosing protocol but not with gastric acidity or in patients with acute Dengue fever. J Nutr. 2000.
- Luo M, Bazargan N, Griffith DP, et al. Metabolic effects of enteral versus parenteral alanyl-glutamine dipeptide administration in critically ill patients receiving enteral feeding: a pilot study. Clin Nutr. 2008.
- Ziegler TR, May AK, Hebbar G, et al. Efficacy and Safety of Glutamine-supplemented Parenteral Nutrition in Surgical ICU Patients: An American Multicenter Randomized Controlled Trial. Ann Surg. 2016.
- European Medicines Agency. Withdrawal of application for the marketing authorisation of Xyndari (glutamine). EMA/521995/2019. October 18, 2019.
- European Commission. EU Register of nutrition and health claims made on foods. Export generated February 14, 2013.
- Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids. National Academies Press. 2005.
Is glutamine safe? Supplements, dose and interactions
Glutamine from food is safe for almost everyone, since it is part of every protein. For supplements, the National Academies could not set an upper intake level, because the data are conflicting and not sufficient for a dose-response assessment.
The only adverse effect they found was a rise in liver enzymes in patients on nutrition drips with about 20 g a day. It went away after stopping. Doses up to 0.57 g per kg a day, about 40 g for a 70 kg adult (our arithmetic), were given without reported adverse effects.
We found no EFSA upper level for glutamine. In the US, glutamine for sickle cell disease is a prescription medicine, and its label lists no contraindications.
- One safe-level estimate. A risk assessment by authors from the Council for Responsible Nutrition, a supplement industry trade group, could not identify a no-effect or lowest-effect dose. That was because no pattern of adverse effects appeared. It set an observed safe level of 14 g a day for healthy adults. That is about twice the 6.84 g from food in the women’s study (our arithmetic). It says much higher doses were tested without harm, but the data were not enough for a confident long-term conclusion. This is one assessment’s finding, not an official limit.
- What trials report. A review of dosing found that single intakes of 20 to 30 g seem to cause no ill effect in healthy adults. Athletes took 28 g a day for 14 days without reported harm, and patients tolerated up to 0.65 g per kg. In 30 older residents, 0.5 g per kg a day for 14 days caused no adverse clinical effects. But blood urea and creatinine rose, and the filtration rate fell 13.3%, against 2.9% on a casein comparison. The authors judged this below the limit of biological significance. A later trial of 12.4 g a day for 60 days in 30 older adults saw no changes and no adverse effects. The label lists side effects that were more common on glutamine in the sickle cell trials. They include constipation (21% against 18%), nausea (19% against 14%), back pain (12% against 5%) and chest pain (12% against 8%).
- Long-term use. A review of side effects notes that some people take about 40 g a day. It warns that large intakes could change how amino acids share transporters, how ammonia is carried, blood amino acid patterns and immune function. It adds that withdrawal could matter, and concludes that long-term studies are needed. Another review finds no evidence that supplements permanently suppress the body’s own production. Yet in the tracer study above, a large load lowered it from 156 to 93 µmol per kg per hour.
- Critical illness. In REDOXS, glutamine with antioxidants was the arm with the highest death rate. The greatest potential for harm was in patients with kidney dysfunction at entry. A reanalysis estimated that a rise in the blood urea-to-creatinine ratio, a marker of catabolism, mediated the extra risk. This is a decision for the intensive care team, and the meta-analysis above does not support routine enteral glutamine.
- Liver, kidney and urea cycle. The National Academies name high blood ammonia and high glutamic acid as the potential hazards of glutamine. In 17 people with cirrhosis, an oral glutamine challenge raised blood ammonia and slowed reaction times, while 4 healthy people saw no change. A 10 g load is used as a test of risk of hepatic encephalopathy (brain effects of liver failure). A review of kidney safety found no significant adverse effects of short-term and long-term use in healthy athletes. But it said glutamine can raise serum creatinine and cause glomerulosclerosis (kidney scarring) in diabetic nephropathy.
- Cancer. Tumor cells use glutamine in the lab, and the National Academies say it is important to ask whether supplements could promote cancer. But in vivo studies (in living organisms) have not confirmed it, and oral glutamine did not enhance tumor growth in rats. A review of 36 clinical studies in cancer patients looked at this. In the great majority, glutamine improved host metabolism or clinical state without increasing tumor growth. Another review says the choice should be individual, and a review of side effects says chronic intake needs to be tested. People in cancer treatment should ask their team.
- Pregnancy, children, medicines and who should ask a doctor. The label says there are no data on use in pregnancy or breastfeeding. Safety and benefit were established only from age 5 in sickle cell disease. The label also says no drug interaction studies have been done, and we found no official list of interactions. People with liver or kidney disease, a urea cycle disorder or cancer should ask a doctor first. So should anyone in hospital, pregnant or on regular medicines, and anyone thinking of more than 14 g a day over the long term.
How to get enough glutamine
- Best food. Of the foods in the Harvard estimates, wheat germ leads with 9.49 g per 100 g, then beef with 1.23 g. Tofu, egg, corn, rice and skim milk give 0.28 to 0.60 g per 100 g.
- Eat enough protein from varied foods. Food supplies about 6.84 g a day in one US study, and the body makes 40 to 100 g. So food is a small share, and no group has a set requirement.
- Skip pills unless a clinician prescribes them. Where glutamine is used as a medicine, in sickle cell disease and in some hospital feeding, a team manages the dose. For gut, sport or blood sugar the trials are small, mixed or negative.
Sources
- Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids. National Academies Press. 2005.
- EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Scientific opinion on dietary reference values for protein. EFSA Journal. 2012;10(2):2557. Version published February 5, 2015.
- Emmaus Medical. ENDARI (L-glutamine) oral powder: prescribing information. US National Library of Medicine, DailyMed. Label version of June 27, 2025.
- Shao A, Hathcock JN. Risk assessment for the amino acids taurine, L-glutamine and L-arginine. Regul Toxicol Pharmacol. 2008.
- Gleeson M. Dosing and efficacy of glutamine supplementation in human exercise and sport training. J Nutr. 2008.
- Galera SC, Fechine FV, Teixeira MJ, et al. The safety of oral use of L-glutamine in middle-aged and elderly individuals. Nutrition. 2010.
- Nóbrega TCM, Silva MARCPD, Rampani EM, et al. Tolerability of glutamine supplementation in older adults: a double-blind placebo-controlled randomized clinical trial. Braz J Med Biol Res. 2024.
- Holecek M. Side effects of long-term glutamine supplementation. JPEN J Parenter Enteral Nutr. 2013.
- Cruzat V, Macedo Rogero M, Noel Keane K, et al. Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation. Nutrients. 2018.
- Hankard RG, Darmaun D, Sager BK, et al. Response of glutamine metabolism to exogenous glutamine in humans. Am J Physiol. 1995.
- Heyland DK, Elke G, Cook D, et al. Glutamine and antioxidants in the critically ill patient: a post hoc analysis of a large-scale randomized trial. JPEN J Parenter Enteral Nutr. 2015.
- Haines RW, Fowler AJ, Wan YI, et al. Catabolism in Critical Illness: A Reanalysis of the REducing Deaths due to OXidative Stress (REDOXS) Trial. Crit Care Med. 2022.
- Oppong KN, Al-Mardini H, Thick M, et al. Oral glutamine challenge in cirrhotics pre- and post-liver transplantation: a psychometric and analyzed EEG study. Hepatology. 1997.
- Romero-Gómez M, Grande L, Camacho I. Prognostic value of altered oral glutamine challenge in patients with minimal hepatic encephalopathy. Hepatology. 2004.
- Davani-Davari D, Karimzadeh I, Sagheb MM, et al. The Renal Safety of L-Carnitine, L-Arginine, and Glutamine in Athletes and Bodybuilders. J Ren Nutr. 2019.
- Kuhn KS, Muscaritoli M, Wischmeyer P, et al. Glutamine as indispensable nutrient in oncology: experimental and clinical evidence. Eur J Nutr. 2010.
- Garlick PJ. Assessment of the safety of glutamine and other amino acids. J Nutr. 2001.
- Lenders CM, Liu S, Wilmore DW, et al. Evaluation of a novel food composition database that includes glutamine and other amino acids derived from gene sequencing data. Eur J Clin Nutr. 2009.
- European Medicines Agency. Withdrawal of application for the marketing authorisation of Xyndari (glutamine). EMA/521995/2019. October 18, 2019.
History of glutamine
Glutamine was first treated as an important molecule in 1873, when indirect evidence showed it was part of proteins. In 1883, abundant free glutamine was found in certain plants. Research took off after Hans Krebs showed in the 1930s that mammalian tissues can both make and break it down.
In the 1950s, Eagle and colleagues reported that cells grown in culture used more glutamine than any other amino acid. In the 1980s, Eric and Philip Newsholme showed that lymphocytes and macrophages (immune cells) use it actively.
In 1990 Lacey and Wilmore asked whether glutamine is a conditionally essential amino acid. They argued that in the critically ill, the body’s need may exceed its ability to make it. Supplements in hospital feeding might then help recovery. That idea drove the trials above.
In 2005 doctors reported two newborns with an inherited failure to make glutamine. The REDOXS trial in 2013 then linked high-dose glutamine to harm in the sickest patients.
In 2017 the FDA approved L-glutamine powder for sickle cell disease. In 2019 the European Medicines Agency reviewed the same product, then named Xyndari in Europe. The review ended with an opinion that the application should be refused. The company withdrew it on September 18, 2019, before the re-examination was complete.
Sources
- Cruzat V, Macedo Rogero M, Noel Keane K, et al. Glutamine: Metabolism and Immune Function, Supplementation and Clinical Translation. Nutrients. 2018.
- Krebs HA. Metabolism of amino-acids: The synthesis of glutamine from glutamic acid and ammonia, and the enzymic hydrolysis of glutamine in animal tissues. Biochem J. 1935.
- Lacey JM, Wilmore DW. Is glutamine a conditionally essential amino acid?. Nutr Rev. 1990.
- Häberle J, Görg B, Rutsch F, et al. Congenital glutamine deficiency with glutamine synthetase mutations. N Engl J Med. 2005.
- Heyland D, Muscedere J, Wischmeyer PE, et al. A randomized trial of glutamine and antioxidants in critically ill patients. N Engl J Med. 2013.
- Emmaus Medical. ENDARI (L-glutamine) oral powder: prescribing information. US National Library of Medicine, DailyMed. Label version of June 27, 2025.
- European Medicines Agency. Withdrawal of application for the marketing authorisation of Xyndari (glutamine). EMA/521995/2019. October 18, 2019.
Frequently asked questions about glutamine
What is glutamine good for?
In the body, it moves nitrogen between organs and fuels gut and immune cells. As a supplement, its use with a drug approval based on a trial is sickle cell disease. There, L-glutamine at 0.3 g per kg twice a day cut median pain crises to 3 from 4 in 230 people. The US FDA approved it in 2017, but the European Medicines Agency’s review did not accept that trial as proof. In intensive care, burns and premature babies, large trials and meta-analyses found no benefit, and REDOXS found more deaths in patients with multiple organ failure.
Is glutamine an essential amino acid?
No, it is not essential. The WHO and EFSA call it conditionally indispensable. That means the body usually makes enough, but severe illness, injury or gut failure can outrun its supply. The National Academies list it as conditionally indispensable in their table, although the text of their glutamine section calls it dispensable. The body makes 40 to 100 g a day, far more than the 6.84 g a day from food in one US study.
What is the difference between glutamine and glutamic acid?
They are two different amino acids. Glutamine is the amide of glutamic acid, with an extra nitrogen group, and the body converts one into the other. The enzyme glutaminase turns glutamine into glutamate and ammonia, and glutamine synthetase does the reverse. Glutamic acid is the taste behind umami and a brain signal, while glutamine is a nitrogen carrier and fuel for gut and immune cells. Trials of one say nothing about the other. See the glutamic acid page.
Does glutamine build muscle or speed recovery?
Mostly not in healthy people. A meta-analysis of 25 trials in athletes found no effect on aerobic fitness, immune function or body composition. In 31 young adults, 0.9 g per kg of lean mass a day for 6 weeks of training added nothing to strength or lean mass. A review of dosing found little support for taking glutamine for immunity, glycogen or anti-catabolic effects in well-controlled studies of healthy, well-fed people. The EU Register lists muscle-related glutamine claims as non-authorized.
Does glutamine help leaky gut or IBS?
Maybe for one kind of IBS, but it needs confirming. In 106 people with IBS and diarrhea after an infection, 15 g a day for 8 weeks was tested. A 50-point symptom drop came in 79.6% on glutamine against 5.8% on placebo, a very large effect from a single trial. For gut permeability in runners in heat, one trial found a lower leak marker and another found it higher. In active Crohn’s disease, a Cochrane review found only two small trials (42 patients) and no clear difference in remission, 44% against 56%.
How much glutamine can you take a day?
No official upper limit exists. The National Academies could not set one, and we found no EFSA limit. One risk assessment by authors from a supplement industry trade group set an observed safe level of 14 g a day for healthy adults. That is not an official limit. Trials used 15 g a day in IBS and 30 g in diabetes. The sickle cell medicine is dosed by weight from 10 to 30 g a day on prescription. Food gives about 6.84 g a day.
What are the side effects of glutamine?
In the sickle cell trials, constipation, nausea, headache, abdominal pain, cough and back, limb and chest pain each affected more than 10% of people. Back pain was 12% on glutamine against 5% on placebo. In older adults, 0.5 g per kg a day raised blood urea and creatinine a little. People with cirrhosis can have a rise in blood ammonia after a glutamine dose. High doses are a concern in kidney disease and urea cycle disorders.
Does glutamine feed cancer?
Tumor cells use glutamine in the lab, but no study has shown that supplements feed tumors in people. The National Academies say in vivo studies have not confirmed the worry. A review of 36 clinical studies in cancer patients found that in the great majority, glutamine did not increase tumor growth. Meta-analyses on mouth sores in cancer patients disagree. People in treatment should ask their oncology team before taking it.