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Supplement

Glutamine

The most abundant amino acid in the body; fuel for the gut and the immune system. Useful mainly in illness or catabolism, less so in healthy people.
Category
Scientific evidence
Moderate
Number of findings
1
Sources
Our own summaries · Cited studies
Recommended dose and how to use
5–10 g/day; in clinical settings, higher doses.

How to take it

5–10 g/day; in clinical settings, higher doses.

Safety

Safe.

Effect by goal · level of evidence

Gut and immunity (severe illness)

improves (modest) Low-moderate RCT (AA)
Small effect

Supports the intestinal mucosa and immunity in situations of catabolism.

View the study (meta-analysis) →

Muscle and performance (healthy people)

no clear effect Moderate RCT (AA)
No effect

Does not increase muscle mass in healthy, well-nourished people.

In depth

⏱ 3 min read

L-glutamine is the most abundant free amino acid in human plasma and skeletal muscle (it makes up more than 60 percent of the plasma pool of free amino acids and approximately 60 percent of the intramuscular pool), an abundance that reflects its multiple biological functions: it is the main energy substrate of enterocytes (the cells of the intestinal epithelium) and of immune system cells (lymphocytes, macrophages), it is a substrate for nucleotide synthesis, it maintains the hepatic glutathione pool, it takes part in renal acid-base balance, and it serves as a nontoxic carrier of nitrogen between tissues for the final elimination of metabolic ammonium.

Clinically, glutamine is classified as "conditionally essential": the body synthesizes it endogenously in adequate amounts under normal conditions, but in situations of severe metabolic stress (trauma, sepsis, extensive burns, major surgery, prolonged extreme exercise, critical illness) consumption exceeds endogenous production and levels fall significantly, which translates into dysfunction of the most dependent tissues (gut and immunity); this characteristic makes glutamine a supplement with specific applications in critical care medicine, clinical nutrition, and recovery in athletes with extreme loads, not a universal ergogenic supplement for healthy people with moderate training.

Intestinal permeability and digestive health

The indication with the strongest mechanistic basis and growing clinical support is improving intestinal barrier integrity in situations of intestinal hyperpermeability: glutamine is the main energy substrate of enterocytes and improves the expression of tight junction proteins (claudins, occludins) between epithelial cells; several small trials have documented improvements in markers of intestinal permeability (urinary lactulose/mannitol, zonulin) and in digestive symptoms with supplementation at 5-30 grams daily for weeks to months.

In post-infectious diarrhea-predominant irritable bowel syndrome, several trials have shown significant improvements in stool frequency and consistency with doses of 15 grams daily divided over 8 weeks, an indication with moderate clinical support and a coherent mechanism.

Critically ill patients and clinical nutrition

In hospitalized critically ill patients, especially burn, trauma, or septic patients, parenteral or enteral glutamine at high doses significantly reduces infectious complications, length of ICU stay, and mortality in some studies, although others (especially the REDOXS trial published in NEJM in 2013) have shown unfavorable trends with very high doses in certain subpopulations; current guidelines recommend glutamine with specific criteria and adjusted doses, not universally.

Post-exercise recovery and immunity in athletes

In athletes with extreme training loads (ultra-distance running, multi-day cycling, intensive military training), where "post-exercise immune depression" increases the risk of respiratory infections, several studies have documented reductions in infection frequency with supplementation during periods of high load; with moderate to moderately intense training, the benefits for performance, recovery, or immunity are quantitatively small, and most people with an adequate protein diet do not benefit from specific glutamine supplementation.

Oral mucositis and radiotherapy

In oral mucositis induced by chemotherapy or radiotherapy, glutamine mouthwashes have shown significant reductions in the severity and duration of the condition in several studies, a practical indication in oncology with reasonable clinical support.

How to take it and precautions

The doses studied vary enormously depending on the indication: for gut health, 5-15 g/day divided into 2-3 doses; for athletic recovery under extreme loads, 5-10 g/day; for oncology-related mucositis, 15-30 g/day divided between an oral rinse and/or oral intake; for critically ill ICU patients, doses adjusted according to protocol; the powder dissolves easily in water and has a neutral taste; capsules are a more practical option for small to moderate doses.

Generally well tolerated; the adverse effects described are rare and mild (mild digestive discomfort at high doses); the most relevant safety considerations are specific: people with advanced liver cirrhosis or hepatic encephalopathy should avoid high doses because of the risk of worsening the encephalopathy (glutamine is a precursor of ammonia); people with cancers that are highly dependent on glutamine (some specific tumors) should exercise theoretical caution because of the role of glutamine in the proliferation of some tumor cells (although clinical data show no clear signals of increased tumor progression with supplementation at usual nutritional doses); in pregnancy and breastfeeding, specific data on use as a supplement are limited, although usual dietary intake is safe; people with monosomy 22 or with glutamate sensitivity may have reactions; glutamine supplements are among the best-selling and most overrated supplements in the sports market: most people with normal training and an adequate protein diet do not obtain significant benefits.

References

  1. Gleeson, M. (2008). Dosing and efficacy of glutamine supplementation in human exercise and sport training. J Nutr 138, 10. doi:10.1093/jn/138.10.2045S
  2. Bertrand, J. et al. (2013). Glutamine restores tight junction protein claudin-1 expression in colonic mucosa of patients with diarrhea-predominant irritable bowel syndrome. JPEN J Parenter Enteral Nutr 37, 4. doi:10.1177/0148607113477603
  3. Heyland, D. et al. (2013). A randomized trial of glutamine and antioxidants in critically ill patients (REDOXS). N Engl J Med 368, 16. doi:10.1056/NEJMoa1212722
  4. Zhou, Q. et al. (2019). Randomised placebo-controlled trial of dietary glutamine supplements for postinfectious irritable bowel syndrome. Gut 68, 6. doi:10.1136/gutjnl-2017-315136
  5. Anderson, P.M.; Lalla, R.V. (2020). Glutamine for amelioration of radiation and chemotherapy associated mucositis during cancer therapy. Nutrients 12, 6. doi:10.3390/nu12061675

Information, not medical advice. Scientific evidence reflects the quality of the studies.

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