Glutamine

What it is

Glutamine is considered a non-essential amino acid, so your body makes it itself. The review by Cruzat and colleagues describes it as the most abundant and most versatile amino acid in the body. Supply is regulated mainly by skeletal muscle, the liver and the gut.

In stress situations, demand can exceed the body’s own production, for example after severe injuries, during infections or after very long, hard exercise. That is why glutamine is also called conditionally essential. Through food it comes with every protein-rich food, that is, with meat, fish, dairy products, eggs and legumes. As a supplement there is free L-glutamine as a powder or in capsules, as well as glutamine dipeptides.

How it is supposed to work

Glutamine is a fuel for cells that divide rapidly. These include the cells of the gut lining and the immune cells. According to Cruzat and colleagues, immune cells use glutamine at a similar or even higher rate than glucose. From this follows the idea: anyone with enough glutamine keeps the gut barrier tight and the immune system functional.

For sport, a second observation was added. After long, hard exercise the glutamine level in the blood falls, and at the same time athletes are more susceptible to infections in such phases. This suggested that glutamine might support immune defense. Gleeson summarizes the experiments on this as follows: glutamine can keep the blood level constant, but it does not prevent the changes in immune function after exercise. The level does not fall far enough to actually slow down the immune cells.

For the gut, the chain of effects is more closely tied to measurements. The permeability of the gut wall can be determined with sugar tests, and here there are studies in which glutamine changes the markers. Whether that also relieves symptoms in each case is a separate question.

Glutamine in sport

The largest analysis on sport comes from Ramezani Ahmadi and colleagues: 47 studies in the review, 25 of them in the meta-analysis. They found no effect on the immune system, endurance performance or body composition. Only body weight fell somewhat more on glutamine. There is thus no basis for muscle building.

For muscle soreness the picture is more open. In a small crossover study with 16 participants, strength returned faster after eccentric leg training, and muscle soreness was lower after 24, 48 and 72 hours. The participants received 0.3 g per kilogram of body weight daily. A systematic review of glutamine and strength recovery, by contrast, found only 6 suitable studies and considered the data insufficient.

For endurance athletes in the heat, glutamine is discussed as protection for the gut wall. Pugh and colleagues found in 10 men running at 30 °C that glutamine lowered the permeability markers, at three different doses. Ogden and colleagues found the opposite in 10 men running to exhaustion at 40 °C: permeability was higher on glutamine. Both studies measure markers in the blood, not symptoms or heatstroke.

What the studies show

Post-infectious irritable bowel 2019: large effect

Randomized, double-blind, placebo-controlled, 8 weeks, 5 g glutamine 3 times daily. 54 participants on glutamine and 52 on placebo completed the study. A reduction in the irritable bowel score of at least 50 points was achieved by 43 on glutamine and 3 on placebo. The authors see this as a basis for larger studies, not as an end point.

Meta-analysis 2019: glutamine in athletes

Ramezani Ahmadi and colleagues analyzed 25 studies in adult athletes. Glutamine changed neither endurance performance nor body composition nor the immune system. Only at very high doses above 200 mg per kilogram did neutrophils fall, and body weight decreased somewhat more.

Intensive care 2013: higher mortality

In the REDOXS trial, 1,223 ventilated patients with multi-organ failure received glutamine, antioxidants, both or placebo. After 28 days, 32.4 % of the glutamine patients had died, compared with 27.2 % without glutamine. In-hospital and 6-month mortality were significantly higher with glutamine. A follow-up study with 1,200 burn patients found neither benefit nor increased mortality.

Sickle cell disease 2018: approval in the US

Niihara and colleagues gave 230 patients aged between 5 and 58 years glutamine or placebo for 48 weeks. On glutamine there were fewer pain crises and fewer hospitalizations, a median of 2.0 versus 3.0. The FDA then approved glutamine. The European Medicines Agency assessed the same study critically because of many study dropouts; the application was withdrawn in 2019.

Where the data stop

The strong irritable bowel finding rests on a single study in a narrowly defined group: people with the diarrhea type after an infection and demonstrably increased gut permeability. Whether glutamine helps in irritable bowel syndrome in general, or in a suspected leaky gut without a diagnosis, has not been studied. The authors themselves call for large confirmatory studies. The sickle cell approval, too, essentially rests on one study that did not convince in Europe.

In sport, the original hypothesis has been refuted as far as studies test it: no effect on performance, muscles or immune defense. For muscle soreness there are only small studies. On the gut barrier in the heat, two small studies contradict each other, and both measure markers instead of symptoms. For critically ill patients in intensive care, glutamine is not a harmless addition: the REDOXS trial found higher mortality there, and the mechanism behind it is unexplained.

Status, approval and legal

In Germany, glutamine is sold as a food supplement. A medicine containing glutamine to be swallowed is not approved in the EU: the application for sickle cell disease was withdrawn in 2019 after the European Medicines Agency had recommended refusal. In the US, L-glutamine powder has been approved for this disease since 2017. There is no official maximum amount for glutamine from EFSA or the BfR. For competitive athletes, the general advice of the German National Anti Doping Agency applies: food supplements can be contaminated, and the Cologne List offers guidance without a guarantee.

Safety

For healthy adults, glutamine is well studied. A risk assessment considers safety up to 14 g daily to be well supported; higher amounts have been tested but are too thinly documented for long-term statements. According to Gleeson, single amounts of 20 to 30 g had no harmful effect, and in one study athletes took 28 g daily for 14 days without harm. In the sickle cell study, mild nausea, fatigue, chest and muscle pain occurred more often on glutamine. The clear warning concerns the critically ill: in ventilated patients with multi-organ failure, mortality was higher with glutamine. Anyone who is seriously ill should take glutamine only after consulting a doctor.

Sources

• Zhou et al., Gut 2019 – post-infectious irritable bowel syndrome, RCT
• Rastgoo et al., Front Nutr 2021 – glutamine plus low-FODMAP, RCT
• Ramezani Ahmadi et al., Clin Nutr 2019 – meta-analysis in athletes
• Gleeson, J Nutr 2008 – dosing and efficacy in sport
• Legault et al., Int J Sport Nutr Exerc Metab 2015 – muscle soreness
• Pugh et al., Eur J Appl Physiol 2017 – gut permeability in the heat
• Ogden et al., Eur J Sport Sci 2022 – gut permeability in the heat
• Heyland et al., N Engl J Med 2013 – REDOXS, intensive care patients
• Niihara et al., N Engl J Med 2018 – sickle cell disease, phase 3
• Shao & Hathcock, Regul Toxicol Pharmacol 2008 – risk assessment of taurine, glutamine, arginine