Clinical effects of glutamine
Sports performance and muscle recovery
Clinical trials have not shown any clear improvement in physical performance (strength, endurance, VO₂max) under glutamine.
A recent meta-analysis (25 trials, adult athletes) concluded that there was no effect on physical fitness and body composition. Similarly, a review (55 studies) noted that glutamine improved some markers of metabolic fatigue (increased glycogen replenishment, less ammonia accumulation) butdoes not increasemeasurable performance.
A randomized trial (Candow et al. 2001) compared 6 weeks of resistance training plus 0.9 g/kg glutamine per day (~30–40 g/d) vs. placebo: gains in strength, lean mass, or muscle catabolism were identical between groups (neutral outcome).
On the other hand, some studies suggest a favorable effect on muscle recovery and inflammation after exercise.
For example, in professional basketball players, 20 days of oral glutamine (6 g/d) during competition decreased blood markers of muscle damage (creatine kinase) and stabilized hormonal balance (catabolism vs. anabolism) without signs of infection.
These data suggest that glutamine could facilitate recovery after intense efforts (reduction of muscular stress).
Summary:On pure athletic performance, glutamine does not show any convincing benefit (neutral results). However, it can positively modulate certain markers of stress and recovery (decrease in CK, C-reactive cytokine, increase in glutathione) after intense exercise. The beneficial effects seem to appear at moderate to high doses (typically ≥0.3 g/kg/day) over several weeks.
Intestinal health (permeability, IBS, post-surgery)
Studies on intestinal permeability and functional disorders indicate a range of outcomes depending on the context.
A notable point concerns irritable bowel syndrome (IBS) of the post-infectious diarrhea type: a randomized controlled trial (8 weeks, 5 g 3×/d = 15 g/d) showed that a clear majority of patients on glutamine achieved a strong improvement (reduction of ≥50 points in the IBS severity score) compared to placebo (79.6% vs 5.8%, p<0.0001).
This treatment also significantly normalized intestinal permeability (lactulose/mannitol test) and reduced stool frequency.
A second trial (addition of glutamine to a low-FODMAP diet in IBS patients) obtained 88% responders (vs. 60% placebo) and 58% mean reduction in IBS score.
These results arevery positivefor IBS with high permeability.
On the other hand, general meta-analyses temper this optimism. A recent review (10 trials, 352 subjects) did not find a significant overall effect of glutamine on intestinal permeability in adults. Only a subgroup at high doses (>30 g/d) in the short term (<2 weeks) showed a small effect (reduced permeability).
In active Crohn's disease, two small trials (total 42 patients) concluded no significant benefit of glutamine (oral or parenteral) on clinical remission or patency.
For digestive surgery or intensive care: some preclinical and intensive care data suggest that glutamine could support mucosal integrity, but clinical meta-analyses have not validated a clear effect in preventing complications (see intensive care immune section).
Globally,positive effects in post-infectious IBS(glutamine 15 g/day x 8 weeks, marked improvement),neutralon permeability in the general population (except high doses), andno proof of effectivenessfor remission of active Crohn's.
Immune support (athletes, intensive care, oncology)
- Sportsmen: glutamine is sometimes used to prevent post-exercise immune depression. In practice, trials are disappointing: meta-analysis in athletes notes no significant effect on the immune system (lymphocytes, neutrophils, incidence of infection). Blood neutrophil counts do not differ consistently with/without glutamine (except perhaps a lower number at very high doses). Consequently, the overall effect on the immunity of athletes isneutral.
- Intensive care: Critically ill patients have a high demand for glutamine. Clinical data are mixed. Nutritional trials (parenteral and enteral, doses 0.3–0.5 g/kg/day) have shown trends towards reduction of nosocomial infections in some long-standing cases, but recent large meta-analyses conclude thatno improvement in mortality or number of infectionsin the majority of critical patients. For example, one meta-analyst (Sun 2020) recommendsnotsystematically add glutamine to intensive care nutrition, except perhaps in severe burns (absence of excess mortality and possibility of slight benefits in this subgroup). Note that a multicenter study (REDOXS, NEJM 2013) even suggested an increase in mortality with high parenteral doses in the most seriously ill (multi-trauma, sepsis). Overall, in intensive care, the effect isnegative or neutral(no net benefit, sometimes risk) on immune status and survival.
- Oncology: Oral glutamine is being studied to reduce chemotherapy/radiotherapy-induced mucositis. In head and neck cancers (HNC), a randomized trial (20 patients vs. 20) showed that oral glutamine significantly reduced the severity of oral mucositis: no grade 4 mucositis in the glutamine group (vs. 25% in placebo) and reduced mean grade (2.9 vs. 3.3, p=0.005).
In conclusion:protective effecton the oral mucosa in oncology (improved mucositis). These results are positive, suggesting that glutamine, by providing a nitrogenous substrate for tissue repair, attenuates the toxicity of treatments.
Immune synthesis:No demonstrated improvement in immune function in athletes or in intensive care (overall neutral/negative). In oncology, on the other hand, the efficacy against side effects (mucositis) ispositive(oral glutamine reduces the severity of RTT mucositis).
Wound healing, oxidative stress and inflammation
Glutamine is involved in cellular metabolism (precursor of glutathione, supporting the synthesis of nitrogenous amino acids for repair), hence the hypothesis of beneficial effects on healing and modulation of oxidative stress. Human data are fragmentary.
- Wound healing: Few trials isolate the effect of glutamine alone. One clinical trial in diabetic patients with foot ulcers used a combination drink (arginine + glutamine + HMB) for 16 weeks.
Overall, no difference in complete healing in the entire population, but a malnourished/ischemic subgroup (albumin ≤ 40 g/L or ankle-brachial pressure index <1.0) saw more healing with supplementation (RR≈1.7, p<0.01).
This suggests that in a state of metabolic stress, nitrogen supplements (including glutamine) may aid wound healing. Overall, however, clinical trials isolating glutamine alone for wound healing are few and show a marginal effect.
- Oxidative stress and inflammation: A controlled trial in men after exhausting exercise (14 days at 0.3 g/kg/d) found a decrease in markers of oxidative stress and inflammation. Malondialdehyde (MDA) and CRP decreased significantly under glutamine, while total antioxidant capacity (TAC) and glutathione increased.
In contrast, the metalloproteinases MMP-2 and MMP-9 remained unchanged.
So,antioxidant/inflammation modulating effectmoderate in humans under physical stress.
Meta-analyses on wound healing and inflammatory response suggest that glutamine may improve nitrogen balance and lower IL-6, TNF-α, CRPpubmed.ncbi.nlm.nih.gov, as well as the lactulose/mannitol ratio (permeability), and even slightly reduce mortality and length of hospitalization in certain critical settingspubmed.ncbi.nlm.nih.govHowever, these analyses often mix critical patients and various nutritional modalities.
Healing/anti-inflammatory synthesis:few clinical trials focused on pure healing. The few available data indicate a modest potential: improvement in antioxidant status and reduction in inflammatory markers (MDA, CRP, IL-6, TNF), but a clinical impact on wound closure not clearly demonstrated (except co-supplementation in complex cases).
Summary conclusion
Overall,Human clinical data on glutamine are mixed. For athletic performance, ergogenicity is disappointing (neutral), but discreet benefits on muscle recovery and oxidative stress have been observed.
Regarding intestinal health, glutamine appears very effective for certain subgroups (e.g., post-infectious IBS with high permeability, IBS-D), while its effect on mucosal integrity in the general population remains uncertain (need for high doses). In terms of immunity, no clear benefit has been observed in athletes or critically ill patients (not recommended for routine use).
In oncology, oral glutamine has been shown to be beneficial in reducing chemoradiotherapeutic mucositis.
Finally, for healing and inflammation, studies suggest a slight protective effect (improved antioxidant status and decreased CRP/IL-6), but no evidence of clinical acceleration of healing.
In summary, glutamine has documented positive clinical effects in certain specific indications (notably IBS-D and oncological mucositis) and for biological markers of recovery or inflammation. Elsewhere, the results are most often neutral., justifying that its use is not systematic outside of these targeted situations. The benefits depend strongly on the dosage (generally high, ~0.3–0.5 g/kg/day) and the population (patients with protein-energy deficiency, specific inflammatory pathology).
Main sources:recent clinical trials and meta-analyses cited above (see references).
