Glutamine and the Liver and Kidneys: Is It Safe
Glutamine is the most abundant amino acid in the blood and muscles, and in sports nutrition it is offered for recovery and immunity. But glutamine is closely tied to ammonia metabolism, which is handled by the liver and kidneys. Are large doses of glutamine safe for these organs? The editorial team examines the physiology, the clinical data and the warning signals.
Glutamine as a nitrogen carrier
Glutamine is a conditionally essential amino acid: a healthy body synthesizes enough of it, mainly in skeletal muscle, but under severe stress, burns or sepsis the need may exceed synthesis. The glutamine molecule contains two nitrogen atoms, so it is the main “safe container” for transferring nitrogen between organs.
The key role of glutamine is to bind toxic free ammonia. In muscle and brain the enzyme glutamine synthetase attaches ammonia to glutamate, forming glutamine, which travels with the blood to the liver, kidneys and intestine. There the enzyme glutaminase splits off ammonia again for further utilization or excretion.
The liver has a clear “zonation”: periportal hepatocytes convert ammonia into urea, while perivenous ones “mop up” residual ammonia by synthesizing glutamine. Thanks to this, almost no free ammonia reaches the general circulation from a healthy liver.
The intestine also actively consumes glutamine as fuel for enterocytes, so a significant part of orally taken glutamine is used up in the intestinal wall and does not reach the blood in full. For an athlete this means that oral glutamine only partly affects plasma levels, and for the liver it means that part of the ammonia load forms already in the intestine.
The role of the kidneys: ammonia and acid–base balance
The kidneys use glutamine to maintain acid–base balance. In the cells of the proximal tubules glutaminase splits off ammonia, which binds hydrogen ions and is excreted in the urine as ammonium, while bicarbonate is formed in parallel and returns to the blood. In metabolic acidosis this mechanism intensifies sharply.
Intense training with high lactate production and a diet with a large amount of animal protein create a moderate acid load, so athletes’ kidneys constantly use glutamine for “buffering.” This is a normal physiological process, not a sign of overload.
When kidney function is reduced, the ability to excrete ammonium and acids decreases, and nitrogenous products may accumulate in the blood. That is why in people with marked kidney failure an additional nitrogen load, including from amino-acid supplements, requires monitoring.
For healthy kidneys, oral glutamine in usual sports doses has no documented harmful effect. Studies analyzed in the review by Gleeson (2008) did not report any worsening of kidney function measures in healthy people.
What is known about safe doses
The risk assessment by Shao and Hathcock (2008) for taurine, L-glutamine and L-arginine set the observed safe level (OSL) for glutamine at 14 g per day for healthy adults. This is not a toxicity threshold but a level for which enough data on the absence of side effects has been accumulated.
Garlick (2001), in a review of amino-acid safety, noted that clinical studies used even higher doses, including intravenously in hospital settings, with no obvious toxic effects in stable patients. However, the amount of data on long-term intake of high doses by healthy people is limited.
| Context | Doses in the literature | Safety conclusion |
|---|---|---|
| Sports supplements | Usually 5–10 g per day | No signals of liver or kidney damage in healthy people |
| OSL from risk assessment | Up to 14 g per day | Safe for healthy adults with long-term intake |
| Sickle cell anemia (prescription drug) | Dosing by body weight per the instructions | FDA-approved drug; physician supervision |
| Critically ill with multiple organ failure | High doses IV and enteral | Increased mortality in the REDOXS study |
The review by Holecek (2013) on the side effects of long-term glutamine supplementation drew attention to theoretical risks: changes in amino-acid metabolism, elevated ammonia and glutamate, effects on the kidneys in sensitive groups. The author called for caution specifically with long-term intake of large doses and in people with liver or kidney disorders.
The effectiveness of glutamine for athletic performance in healthy, well-nourished people remains doubtful. Gleeson (2008) found no convincing evidence of improved performance or immune measures, so the benefit/risk ratio for large doses does not favor increasing them.
A signal from intensive care
The most serious data on the danger of glutamine come not from sport but from intensive care. The randomized REDOXS study (Heyland et al., 2013) in the New England Journal of Medicine enrolled more than 1,200 critically ill patients with multiple organ failure. High doses of glutamine did not improve outcomes, and the glutamine group showed higher mortality.
Especially alarming was the subgroup of patients with kidney dysfunction at the start of the study. After this, the ESPEN guideline on nutrition in intensive care (Singer et al., 2019) recommends not prescribing additional intravenous glutamine to unstable patients, in particular those with liver or kidney failure.
These data do not transfer directly to a healthy person taking a few grams of glutamine after training. However, they clearly show that with impaired liver and kidney function the body copes worse with extra nitrogen, and a “harmless amino acid” can become a risk factor.
The editorial team’s practical conclusion: if you or those close to you have severe kidney or liver disease, the use of glutamine supplements should be discussed with a doctor, even if the product is sold as ordinary sports nutrition.
Cirrhosis, CKD and other risk groups
In liver cirrhosis the ability to convert ammonia into urea is reduced, and glutamine, which releases ammonia in the intestine and kidneys, could theoretically worsen hyperammonemia. Ammonia is linked to hepatic encephalopathy, so patients with cirrhosis are not advised to take glutamine on their own.
In chronic kidney disease the main issues are the overall nitrogen load and protein control, as set out in the KDOQI guideline (2020). Glutamine adds nitrogen, so its use should be accounted for in the overall nutrition plan agreed with a nephrologist.
People with epilepsy and some neurological conditions should also be cautious: glutamine is a precursor of glutamate, an excitatory neurotransmitter. There is little direct evidence of harm from supplements in this group, but caution is justified.
- Cirrhosis and hepatic encephalopathy — do not take without a hepatologist.
- CKD stage 3–5 — only within the prescribed diet.
- Critically ill — only at the decision of an intensive-care physician.
- Healthy athletes — up to 14 g per day is considered a safe level.
For monitoring, liver function tests, creatinine with GFR, urea and, if needed, blood ammonia are useful, but the latter is measured only on clinical indications.
Editorial conclusions
Glutamine is a central molecule of nitrogen metabolism, and the liver and kidneys work with it constantly. For healthy people, at doses up to 14 g per day, no serious risks to these organs have been found.
The danger signal comes from intensive care: in critically ill patients, especially with kidney dysfunction, high doses of glutamine are associated with higher mortality. In cirrhosis and CKD the supplement can worsen the balance of ammonia and nitrogen.
Since the athletic effectiveness of glutamine in healthy people is doubtful, the editorial team sees no point in large doses.
We also advise reading our materials on glutamine and athletes’ immunity, on ammonia and fatigue during training, and on nitrogen balance on a high-protein diet.
References
- Shao A, Hathcock JN. Risk assessment for the amino acids taurine, L-glutamine and L-arginine. Regul Toxicol Pharmacol. 2008;50(3):376–399.
- Garlick PJ. Assessment of the safety of glutamine and other amino acids. J Nutr. 2001;131(9 Suppl):2556S–2561S.
- Gleeson M. Dosing and efficacy of glutamine supplementation in human exercise and sport training. J Nutr. 2008;138(10):2045S–2049S.
- Holecek M. Side effects of long-term glutamine supplementation. JPEN J Parenter Enteral Nutr. 2013;37(5):607–616.
- 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.
- Singer P, Blaser AR, Berger MM, et al. ESPEN guideline on clinical nutrition in the intensive care unit. Clin Nutr. 2019;38(1):48–79.
- Ikizler TA, Burrowes JD, Byham-Gray LD, et al. KDOQI clinical practice guideline for nutrition in CKD: 2020 update. Am J Kidney Dis. 2020;76(3 Suppl 1):S1–S107.
Andriy Melnyk
A strength-sports coach and author of programs for beginner and intermediate levels. Writes about training planning.
