L-Glutamine/Glutamic acid
Also known as: Glutamine, L-glutamine, glutamic acid, glutamate, C₅H₁₀N₂O₃, C₅H₉NO₄, L-Glutamine
Overview
L-Glutamine is the most abundant free amino acid in the human body, considered conditionally essential during periods of catabolic stress such as critical illness or intense exercise. Glutamic acid, a non-essential amino acid, is a key neurotransmitter and metabolic intermediate. Both are naturally found in high-protein foods like meat, dairy, eggs, and legumes, and are available as dietary supplements. Supplemental L-Glutamine is primarily investigated for its roles in maintaining gut barrier integrity, modulating immune responses, and supporting recovery in clinical settings like critical illness or post-surgery. It serves as a major fuel source for enterocytes and immune cells, while glutamic acid is crucial for neurotransmission and is a precursor for GABA. The research maturity for L-Glutamine is moderate to high in specific clinical contexts, but less robust for general wellness or athletic performance. Evidence for direct glutamic acid supplementation is limited.
Benefits
L-Glutamine's benefits are primarily observed in specific clinical populations under stress, with limited evidence for healthy individuals. For gut barrier function, a meta-analysis found no significant overall effect on intestinal permeability, but subgroup analysis suggested a small reduction with very high doses (>30 g/day) for short durations (<2 weeks), though the clinical significance is uncertain. In surgical patients, particularly those undergoing colorectal cancer surgery, L-Glutamine has been shown to improve humoral immune markers (IgA, IgG, IgM) and the CD4+/CD8+ ratio, but it did not significantly reduce postoperative complications or hospital stay. For critically ill adults, a systematic review of 47 RCTs found no reduction in hospital mortality with L-Glutamine supplementation. While some limited evidence suggests L-Glutamine may support muscle protein synthesis during catabolic stress, these effects are inconsistent and generally small in healthy, exercising adults. Overall, effect sizes are generally small and of uncertain clinical relevance, with benefits, when present, more likely in specific subgroups or under severe physiological stress.
How it works
L-Glutamine functions as a primary energy source for rapidly dividing cells, including enterocytes (gut lining cells) and lymphocytes (immune cells), thereby supporting gut barrier integrity and immune function. It also plays a crucial role in glutathione synthesis, acting as a precursor for this important antioxidant, and helps modulate inflammatory responses. Glutamic acid, on the other hand, primarily acts as an excitatory neurotransmitter in the central nervous system. It participates in the glutamate-glutamine cycle in the brain, which is vital for neuronal communication, and is involved in various amino acid metabolic pathways. Both amino acids interact with multiple transporters and enzymes involved in nitrogen metabolism. Oral L-Glutamine is well absorbed, with plasma levels typically peaking within 30–60 minutes, though very high doses (>30 g/day) may saturate intestinal uptake mechanisms.
Side effects
L-Glutamine is generally well tolerated in clinical studies, even at high doses up to 0.5 g/kg/day. The most commonly reported side effects, occurring at very high doses, are mild gastrointestinal discomfort such as bloating and gas. Uncommon or rare serious adverse events directly attributed to L-Glutamine supplementation have not been frequently reported in meta-analyses. There are no well-documented significant drug interactions, though a theoretical risk of increased ammonia exists in patients with severe liver dysfunction, warranting caution. L-Glutamine is contraindicated in critically ill patients with multiorgan failure due to a lack of benefit and potential for harm in some subgroups. Safety in pregnancy and lactation has not been established, and while there are no specific concerns for elderly or pediatric populations, evidence in these groups is limited. Long-term safety in healthy populations is less thoroughly studied.
Dosage
The minimum effective dose for L-Glutamine is not well established, but clinical trials often use 0.3–0.5 g/kg/day in clinical settings. For specific effects on gut permeability, doses exceeding 30 g/day may show a small effect, though the clinical relevance remains unclear. In general wellness or athletic performance contexts, there is no established effective dose, and typical supplemental doses range from 5–20 g/day, despite a lack of strong evidence for benefit. The maximum safe dose appears to be up to 0.5 g/kg/day in short-term studies, with doses above 30 g/day potentially causing gastrointestinal discomfort. Timing considerations are not well studied, but divided doses may improve tolerance. L-Glutamine is available in oral (powder, capsules) and parenteral forms, with no clear advantage of one form over another in clinical trials. Absorption is efficient but can saturate at very high doses, and no specific cofactors are required.
FAQs
Is glutamine effective for leaky gut?
Evidence is mixed. High-dose glutamine (>30 g/day) may reduce intestinal permeability in the short term, but the effect is small and of uncertain clinical significance. No robust evidence supports its use in healthy individuals.
Does glutamine boost immunity?
In surgical patients, glutamine may modestly improve some immune markers, but it does not clearly reduce infections or complications. There is no consistent benefit in healthy adults.
Is glutamine safe long-term?
Short-term use is generally well tolerated, but long-term safety data are limited, especially in healthy populations. Caution is advised in individuals with severe liver disease.
When should I take glutamine?
Timing is not well established. Divided doses may improve tolerance. There is no strong evidence for specific timing relative to exercise or meals.
Are there drug interactions?
No significant drug interactions are well-documented. However, caution is advised in patients with severe liver disease due to a theoretical risk of increased ammonia levels.
Research Sources
- https://pubmed.ncbi.nlm.nih.gov/39397201/ – This systematic review and meta-analysis of 10 RCTs (n=352) investigated glutamine's effect on intestinal permeability. It found no significant overall effect but noted a small reduction with doses >30 g/day for durations <2 weeks, though the clinical relevance is uncertain due to heterogeneity and small effect size.
- https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2021.765809/full – This meta-analysis of 31 RCTs (n=2,201) in colorectal cancer patients post-surgery found that glutamine improved humoral immune markers (IgA, IgG, IgM, CD4+/CD8+ ratio). However, it did not significantly reduce postoperative complications or hospital stay, suggesting immune modulation without clear clinical outcome improvement.
- https://apm.amegroups.org/article/view/56468/html – This systematic review and meta-analysis of 47 RCTs in critically ill adults concluded that glutamine supplementation did not reduce hospital mortality, regardless of dose or route. The study highlights the lack of benefit in this vulnerable population and suggests potential harm in some subgroups.
