Glutamine
L-glutamine

Glutamine is an amino acid, and amino acids are the bricks proteins are built from. It is the most abundant of those circulating free in the blood, and the body makes it on its own: an estimated 40–80 grams a day.

It also arrives with food, inside proteins: glutamine and glutamate together make up between 5% and 15% of dietary protein, about 6.84 grams of glutamine a day on average in the cohort of US nurses where it has been measured.

A serving from the tub is generally 5 grams. Next to what the body already produces, that amounts to between 6% and 12.5%.

Glutamine is called a conditionally essential amino acid: under normal conditions the body makes all it needs, but in certain states of metabolic stress demand can outstrip the capacity to make it. This is documented in people with trauma, major surgery, sepsis, burns and critical illness, where glutamine in muscle and blood falls. It is a concept from the physiology of stress, not a demonstration that a healthy adult who supplements gets anything.

The same molecule occupies two different legal boxes. In the European Union it is sold as a food supplement, which legally is a food: the product needs no prior authorization and cannot claim to prevent or treat any disease. In the United States, the tub is sold as a dietary supplement, a category that does not require prior authorization of the product. In the United States there are also two glutamine medicines, with an authorized indication and prescribing information behind them. There is no harmonized maximum dose in the European Union: some Member States set their own and others set none.

Its documented functions are several, and none of them looks like that of a nutrient missing from a normal diet. It is a precursor of the nucleotides from which DNA and RNA are built, it takes part in regulating acid-base balance through the renal production of ammonia, and it serves as a substrate for making glucose. It is an amino acid in heavy traffic, and that is precisely why an oral dose of 5 grams is hard to tell apart from the background noise.

Glutamine has been studied in digestion, strength, recovery after exercise, immune defenses and mental performance.

Digestion. A trial in people with diarrhea-predominant irritable bowel syndrome that appeared after an infection found a much greater improvement in symptoms than with placebo. It is a single trial, done at one center, and no independent replication has been located.

Strength and muscle mass. The trial that put it to the test, alongside six weeks of strength training, found no difference at all between the glutamine group and the placebo group.

Recovery after exercise. Two small trials find favorable signals: in one, less muscle soreness and somewhat more strength recovered; in the other, fewer markers of muscle damage in the blood. Neither of the two measured athletic performance.

The athlete’s immune defenses. The starting idea, that prolonged exercise empties glutamine and that it has to be replaced to avoid falling ill, has been questioned in humans since 2002.

Brain. We have located only one trial, with a single 2-gram dose in healthy adults. It improved nothing of what it measured, and on one of the tasks those who took glutamine actually made more errors.

In the hospital, it is another matter. Glutamine is a medicine authorized in the United States for two specific diseases, and in intensive care it is given into a vein. All of that belongs to another molecule, another route or seriously ill patients, and is not equivalent to what is in a tub.

The European Food Safety Authority assessed two applications on glutamine, one on immune health and another on the integrity of the intestinal barrier, and neither of the two went on to be authorized. We have not located any health claim on glutamine authorized in the European Union.

Digestion. The digestive trial did not measure only how the patients felt. It measured the frequency and consistency of bowel movements and, with a test of two sugars that are drunk and then collected in urine, intestinal permeability: how far the intestinal wall lets through what it should not. Everything moved in the same direction. Two things are worth knowing about it: the placebo was not inert, it was whey protein, and it is not confirmed that it supplied the same nitrogen; and the population had a diagnosis, they were not healthy people with complaints.

Strength, recovery and performance. The three trials we have used point in different directions. The one that trained strength for six weeks found nothing. The two that measured recovery found something: less soreness and somewhat more strength recovered in one, fewer markers of muscle damage in the blood in the other. None measured whether anyone ran faster, jumped higher or lifted more weight. All three compare glutamine with maltodextrin or starch, which supply no nitrogen, so none of them answers whether what was observed is down to the amino acid or to taking a little more protein.

Glutamine does not appear on the World Anti-Doping Agency Prohibited List in force since January 1, 2026.

Brain. The biochemical route exists: glutamine crosses the barrier that protects the brain, glutamate does not, and that is why the brain makes its own glutamate mostly from glutamine, which is in turn a precursor of GABA. From there to a promise about mood or calm is a short step, and that is where the chain breaks: that cycle is tightly regulated by the brain’s support cells. On mood, sleep and anxiety, the search for trials of glutamine alone against placebo was done and came up empty.

There is a methodological problem that runs through this entire page, and it is worth seeing once and for all. None of the five trials that support it compared glutamine with an equivalent amount of nitrogen. Four used maltodextrin, starch or cellulose, which supply no nitrogen at all. The fifth, the digestive one, used whey protein, which does supply it, but there is no record that the amount was matched. The consequence is the same across the three axes: when an effect appears, what glutamine does cannot be separated from what any other equivalent protein intake would do. It is not the flaw of one particular study, it is a hole in the field.

On intestinal permeability during exercise there is one trial that found a dose-dependent attenuation with the two-sugar test, and a later one that, with a single dose within that range, found nothing. The direction is documented; the magnitude is not, because the figures from that work are still pending verification against the article. And in both cases what is measured is a biomarker, not a symptom.

What happened in the hospital. In the United States there are two authorized glutamine medicines: one for sickle cell disease, since 2017, and another for short bowel syndrome, since 2004 and only in combination with a growth hormone. The European medicines agency examined the same sickle cell dossier, its committee issued a negative opinion in 2019 because the main study did not show that it reduced crises or hospital admissions, and the company withdrew the application. These are medicines authorized for specific diseases, and comparing them with a tub does not establish that one replaces the other.

The trials of oral glutamine do not sketch a profile of a healthy person for whom glutamine would be of any use. It has been studied in people with one specific digestive problem, in young people doing strength training, in athletes under heavy load, in university students and in patients with diseases that are treated with glutamine as a medicine. Of all those groups, only in the first did a large effect appear, and it still has not been repeated.

The groups studied here in which glutamine has shown something are defined by a disease or by a high training load, and in none of them has it been shown that the effect comes from the amino acid and not from the extra protein intake. To a healthy person on an adequate diet, the available evidence offers no reason. And anyone with one of the diseases that are treated with glutamine is not facing a supplement, but a clinical decision that belongs to their doctor.

The trials in healthy people have not all used the same amount. Some give a fixed amount, such as the 2 grams in a single serving in the mental performance trial or the 6 grams a day for twenty days in the trial in basketball players. Others calculate it from body weight, and then the daily amount comes out higher. The digestive trial, done in patients, used 15 grams a day split into three servings over eight weeks.

The amounts listed for the glutamine medicines are far higher and are set for specific diseases, on prescription. They are not intake guidelines or Suplepedia recommendations.

None of the above is medical advice. Anyone considering taking glutamine, and especially anyone on a treatment or with a disease, would do well to discuss it first with their doctor or pharmacist.

A risk assessment published in 2008 set at 14 grams of supplement a day the amount up to which the evidence of absence of adverse effects is solid. Above that figure, what is missing is enough data for a long-term safety conclusion, which is not the same as having found harm. It is not an official limit. None of the agencies we have consulted has set a maximum for glutamine, and several explain that the available data do not allow one to be set. Its two authors belonged to a supplement-industry trade association and declare as much in the article: Shao A, Hathcock JN. Regul Toxicol Pharmacol 2008;50(3):376–399. DOI 10.1016/j.yrtph.2008.01.004

The doses of the oral trials that support this page, exactly as each one set them. They are not recommendations.

Two rows have been left out on purpose. The doses from the permeability trial in runners are not included because its figures are still pending verification against the article. And the maximum intake figures from two official bodies, one Norwegian and one Spanish, are not either: neither of the two documents has been opened, and a limit figure that has not been read in its source does not reach this page.

On a formal maximum limit, the agencies we have consulted have set none, and several say so for the same reason: the available data do not allow a dose-response analysis.

The authorized dosing regimens, in descriptive mode and only so that the distance can be seen. The medicine for sickle cell disease is given at 5, 10 or 15 grams twice a day according to the patient’s body weight band. The one for short bowel syndrome, 30 grams a day split into six servings, for a maximum of sixteen weeks and in combination with a growth hormone. These are regimens for medicines for specific diseases, on prescription, and they do not establish that a supplement can replace them or the other way around.

A good part of the glutamine that is swallowed never reaches the general circulation: the gut and the liver take it out along the way. One study in humans put that removal at 66.7%, a figure still pending verification against the original article. In people who already have normal levels, what is described is that supplementing does not appreciably raise glutamine in the blood.

That removal has a name: splanchnic first pass, the toll charged by the gut and the liver on what arrives through the digestive tract before it passes into the general circulation. With glutamine the toll is high, and on top of that the gut and the immune cells consume it, so that a good part is spent where it is absorbed. The same study that measured it compared free glutamine with glutamine that came inside a protein and found that the two are retained equally, which undercuts the idea that taking it loose is a privileged route.

The dipeptide does raise glutamine in the blood markedly: a single oral 20-gram serving in adults raised the plasma glutamine concentration by 794 µmol/L above baseline. The direct comparison in people between one and the other at equivalent amounts is still open.

The kidney barely takes part in elimination. Glutamine is filtered in the glomerulus but the tubules reabsorb it almost completely. The body does not get rid of it: it recovers it and uses it.

No. In the powder tub there is almost always free L-glutamine. In the hospital another molecule is often used: a dipeptide called alanyl-glutamine, which carries glutamine bonded to another amino acid.

The reason for the switch is chemical. Free glutamine is unstable in water and poorly soluble, and it does not withstand the heat sterilization that a solution intended for a vein requires. The dipeptide was synthesized to solve that problem, not because it worked better.

The consequence matters when reading studies: part of the best-designed research was done with the dipeptide and by the intravenous route, and it does not speak about the powder.

The specific chemical problem is that free glutamine, in aqueous solution and with heat, cyclizes to pyroglutamic acid and releases ammonia. That is why it cannot be part of a preparation for a vein, which is sterilized by heat. Fürst and Stehle synthesized, for that reason, dipeptides containing glutamine, heat-stable and highly soluble, which the body splits quickly, releasing the glutamine; they have been available for parenteral nutrition since 1994.

Given the absence in our search of peer-reviewed analyses of commercial products or documents from the certifiers, we choose to name none in this section.

There is indeed a pharmacopoeia monograph that sets identity and purity criteria for glutamine as a raw material, and it is worth understanding what it does and what it does not do. It defines how to identify the substance, the range its assay must fall within and which impurities are allowed, and it serves so that a manufacturer can buy raw material meeting a standard. It says nothing about the finished product that reaches a shelf: neither about what was added to it afterwards, nor about whether the label declares what the tub contains. Between the raw-material standard and the tub there is a gap that closes only by analyzing commercial products, and those analyses are precisely what is missing. We do not reproduce the values of the monograph here because we have not read it directly.

“It repairs leaky gut,” in more detail. The images of intestinal cells multiplying with glutamine are real and they are from the laboratory: tissue in a dish, not an intestine inside a person. In people, the only placebo-controlled trial that found an improvement in permeability in patients with a digestive diagnosis has no independent replication. In runners exposed to heat the signal appeared with doses calculated by body weight, and a later trial with an intermediate dose from that same range found nothing. In every case what is involved is a surrogate biomarker, a laboratory measure used as an approximation to what really matters, not a symptom or a disease.

“It stops you losing muscle,” in more detail. To the negative trial is added the regulator: the European authority also assessed the claim applications on maintenance of muscle mass, and none of those was authorized either.

“Five grams change something next to what the body already produces.” It is the myth that holds up the rest. Five grams are a small fraction of what the body makes each day, of the same order as what the diet already supplies, and of that dose a good part stays in the gut and the liver before reaching anywhere else. That does not prove that supplementing does nothing; it explains why finding an effect is so hard.

Long-term studies in healthy people are missing. The digestive finding still has no independent replication. And none of the trials that support this page compared glutamine with another equivalent source of nitrogen, so it remains unanswered whether what is observed is an effect of the amino acid or of taking a little more protein.

There are three more gaps. It is not known whether the passing rise in blood glutamine after a dose translates into anything real in the tissues of someone who already has normal levels. It is not settled whether the dipeptide, which does raise glutamine in the blood, does anything different from the powder when taken by mouth. And there is no established dose either: each trial chose its own, some with a fixed amount and others by kilogram of body weight, which makes the results hard to compare with one another.

Two more gaps, of another kind. The first is that there is no dose-response program on clinical outcomes: the two works that compared several doses measure a permeability biomarker and digestive tolerance, not a benefit. That is why no agency has been able to set a maximum limit with method: the available data do not allow a dose-response analysis. The second is that there are no accessible degradation constants with which to compare the stability of free glutamine and that of the dipeptide, so the statement that one is more stable than the other is qualitative and is kept that way on this page.

And a note on how to read all of the above: that data are missing does not mean that glutamine is dangerous or that it is useless. It means that the questions a buyer rightly asks do not yet have a measured answer.

The prescribing information for the glutamine medicine approved in the United States for sickle cell disease states that there are no data on its use during pregnancy, nor on its passage into breast milk, nor on its safety in people with impaired liver or kidney function, and that its safety in children under five is not established. Absence of data is not absence of risk: it means it has not been studied.

In people with cirrhosis, an oral serving of glutamine raises ammonia in the blood, something that was not seen in the control group without cirrhosis in the same study. The direction of that effect is documented; its exact magnitude is not.

In older people on high doses, changes in kidney function parameters have been described.

Outside those cases, what the sources consulted describe in healthy people are headaches and digestive complaints, such as loose stools and abdominal discomfort, which increase with the dose. That nothing else has been described is not the same as nothing else existing.

This section describes, it does not advise. Anyone on a treatment, with a liver or kidney disease, pregnant or breastfeeding would do well to discuss it with their doctor before taking any supplement.

On interactions with medicines, the prescribing information for the glutamine medicine authorized in the United States says literally that no interaction studies have been carried out. That does not mean there are none: it means they have not been looked for.

A caution with antiepileptics circulates, built on a reasonable chain: glutamine is a precursor of glutamate, which is an excitatory neurotransmitter, and from there to a possible effect on the seizure threshold. We have not located any trial or any published case documenting that interaction in people. It is a mechanistic hypothesis and it is presented as such: it is neither asserted nor ruled out.

With cancer something similar happens, and in the opposite direction to the alarm. That tumor cells consume glutamine avidly is described in the laboratory and in animals, and it varies a great deal with the type of tumor. In people we have not located evidence that supplemental glutamine makes a tumor grow, and the review by the US Institute of Medicine (now the National Academy of Medicine) points the other way. This page is not a basis for any decision in cancer treatment; that conversation belongs to the oncologist.

In people with diabetes, effects on gut hormones, on insulin and on glucose after eating have been described. They are not described as harmful in the short term, and their authors note that more studies are needed.

The most complete safety data that exist do not come from supplements but from the prescribing information of a medicine, and that conditions how they have to be read. They come from two pooled placebo-controlled trials, with 187 patients in the glutamine arm and 111 in the placebo arm, all with sickle cell disease or beta-zero thalassemia and between 5 and 58 years old. They are not healthy people.

The adverse reactions that exceeded 10% incidence were constipation, nausea, headache, abdominal pain, cough, pain in an extremity, back pain and chest pain. Their exact percentages have not been verified. In fact, 2.7% of the patients, five people, discontinued treatment because of adverse reactions.

There were three deaths among the 187 in the glutamine arm and none in the placebo arm. The prescribing information states that none was considered related to treatment and that serious adverse reactions were more frequent in the placebo group and consistent with the underlying disease. The three things go together or none of them goes: the isolated figure alarms without informing.

In healthy people, the work that measured digestive tolerance with three increasing doses found more cumulative symptoms with the highest one, and concluded that even that one was well tolerated, with mild complaints in some of the participants. Earlier works described good tolerance with oral doses per kilogram of body weight in the same range.

The rise in ammonia in cirrhosis even has a procedure name, the oral glutamine challenge, and it has been proposed as a way of identifying patients at risk of hepatic encephalopathy. That it happens in people with cirrhosis and not in controls is documented by more than one group. The magnitude of the rise is not carried over here because none of the series has been verified against its primary source.

On the kidney, the available data arrive indirectly: in institutionalized older people who received high doses, a rise in creatinine and a fall in estimated glomerular filtration rate were described, and it also happened in the group that received casein, so it cannot simply be attributed to glutamine. The recommendation that accompanies that finding is to monitor kidney function and ammonia in older people on high doses, and it is a clinical recommendation, not ours.