L-glutamine

L-glutamine, C₅H₁₀N₂O

Evidence: Moderate

L-Glutamine is the most abundant amino acid and a primary fuel for intestinal cells. It directly supports the repair and maintenance of the gut lining and barrier. This is crucial for preventing increased gut permeability ('leaky gut') and preserving overall gut integrity.

There are 56,110 peer-reviewed scientific studies on this ingredient.

Selected Study 1/2:

Achamrah N, Déchelotte P, Coëffier M. Glutamine and the regulation of intestinal permeability: from bench to bedside. Curr Opin Clin Nutr Metab Care. 2017 Jan;20(1):86-91. doi: 10.1097/MCO.0000000000000339. PMID: 27749689.

Study Summary:

Study type: Narrative review synthesizing recent cell, animal and small human studies on L-glutamine and intestinal barrier function; it reports no new participants of its own.

Observed benefits: Across models, glutamine supplementation curtailed villus atrophy, restored claudin-, occludin- and ZO-1 expression, reduced paracellular leak and improved clinical or biomarker indices of gut permeability in settings such as critical illness, exercise stress and post-infectious IBS.

Mechanisms of action: The authors highlight glutamine’s role as the preferred fuel for enterocytes and immune cells; its provision preserves ATP, attenuates NF-κB–driven inflammation, boosts glutathione, modulates mTOR and MAPK signalling, up-regulates tight-junction gene transcription and limits epithelial apoptosis—collectively sustaining barrier integrity.

Side effects: Safety data are sparse but generally reassuring. The review notes no consistent adverse events at usual oral doses, and a subsequent 10-day ICU RCT reported “no adverse events attributable to glutamine.”

Strength of evidence: Pre-clinical findings are robust and coherent, yet human evidence remains limited to heterogeneous, under-powered trials; therefore the review judges the clinical evidence as only moderate and calls for larger, well-controlled RCTs before routine supplementation can be recommended.

Selected Study 2/2:

Kim, M., & Kim, H. (2017). The Roles of Glutamine in the Intestine and Its Implication in Intestinal Diseases. International Journal of Molecular Sciences, 18(5), 1051. https://doi.org/10.3390/ijms18051051

Study Summary:

Study type: Narrative review pooling ≈140 cell, animal and human studies on intestinal L-glutamine; it reports no new participants of its own.

Observed benefits: Across experimental models, glutamine boosts enterocyte proliferation, up-regulates tight-junction proteins, cuts apoptosis and dampens pro-inflammatory signaling, preserving barrier integrity and mucosal healing. Clinical data cited in the review—and confirmed by an 8-week randomized trial in 106 post-infectious IBS patients—show reduced intestinal permeability and large improvements in bowel-symptom scores, with similarly favorable trends in trauma, sepsis and short-bowel cohorts.

Mechanisms of action: Benefits are linked to MAPK activation and optimisation of growth-factor signalling (EGF, IGF-I), induction of claudin-1/4, occludin and ZO-1-3, inhibition of NF-κB and STAT pathways, enhanced glutathione-dependent antioxidant defence and HSP expression, plus relief of ER stress via mTOR inhibition and autophagy promotion; emerging work also suggests microbiota modulation.

Side effects: The review notes glutamine is “generally safe” at clinical doses (≤15 g/day), with no consistent adverse events. A focused JPEN review warns that chronic high intakes (~40 g/day) might disturb amino-acid transport, raise ammonia and conceivably influence tumor growth, though human evidence is scarce. The IBS RCT reported low, similar minor-event rates in glutamine and placebo groups and no serious events.

Strength of evidence: Mechanistic and pre-clinical findings are robust, but human trials remain small, heterogeneous and sometimes conflicting; the authors therefore judge current clinical support as moderate and call for larger, standardized RCTs before routine supplementation can be recommended.