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Glutamine is thought to have beneficial effects on the metabolic and stress response to severe injury. Clinical trials involving patients with burns and other critically ill patients have shown conflicting results regarding the benefits and risks of glutamine supplementation. In a double-blind, randomized, placebo-controlled trial, we assigned patients with deep second- or third-degree burns (affecting ≥10% to ≥20% of total body-surface area, depending on age) within 72 hours after hospital admission to receive 0.5 g per kilogram of body weight per day of enterally delivered glutamine or placebo. Trial agents were given every 4 hours through a feeding tube or three or four times a day by mouth until 7 days after the last skin grafting procedure, discharge from the acute care unit, or 3 months after admission, whichever came first. The primary outcome was the time to discharge alive from the hospital, with data censored at 90 days. We calculated subdistribution hazard ratios for discharge alive, which took into account death as a competing risk. A total of 1209 patients with severe burns (mean burn size, 33% of total body-surface area) underwent randomization, and 1200 were included in the analysis (596 patients in the glutamine group and 604 in the placebo group). The median time to discharge alive from the hospital was 40 days (interquartile range, 24 to 87) in the glutamine group and 38 days (interquartile range, 22 to 75) in the placebo group (subdistribution hazard ratio for discharge alive, 0.91; 95% confidence interval [CI], 0.80 to 1.04; P = 0.17). Mortality at 6 months was 17.2% in the glutamine group and 16.2% in the placebo group (hazard ratio for death, 1.06; 95% CI, 0.80 to 1.41). No substantial between-group differences in serious adverse events were observed. In patients with severe burns, supplemental glutamine did not reduce the time to discharge alive from the hospital. (Funded by the U.S. Department of Defense and the Canadian Institutes of Health Research; RE-ENERGIZE ClinicalTrials.gov number, NCT00985205.).

Purpose Radiation-induced oral mucositis (RIOM) severely impacts patients with head and neck cancer (HNC) undergoing radiotherapy, often leading to pain and malnutrition. L-arginine and glutamine are immune-enhancing amino acids with potential benefits in wound healing and inflammation control. This study evaluated the efficacy of L-arginine versus L-glutamine oral suspensions in managing RIOM. Methods In this triple-blind, randomized controlled trial, 69 HNC patients with RIOM were allocated to three groups ( n  = 23 each): Group I (L-arginine 5 g + maltodextrin 5 g), Group II (glutamine 5 g + maltodextrin 5 g), or Group III (maltodextrin 10 g). Outcomes, assessed at weeks 2, 5, and 7 of radiotherapy, included the WHO oral mucositis scale, Pain Visual Analogue Scale (Pain-VAS), body mass index (BMI), and Oral Health Impact Profile (OHIP-14) questionnaire. Results By week 5, WHO scale scores differed significantly among groups ( p  < 0.001), with arginine and glutamine groups exhibiting lower mucositis severity than the maltodextrin group. Pain-VAS scores at weeks 5 and 7 were significantly lower in the arginine and glutamine groups compared to maltodextrin ( p  = 0.004 and p  < 0.001, respectively). By 7th week of radiotherapy, BMI was significantly decreased in the maltodextrin group than in either the arginine ( p  = 0.028) or glutamine ( p  = 0.001) groups, indicative of treatment-mediated weight loss. In contrast, the BMI over time in the arginine ( p  = 0.87) and glutamine ( p  = 0.170) groups were almost constant. This indicates that compared to maltodextrin alone, both amino acid supplements prevented a decline in BMI during radiotherapy. OHIP-14 scores improved significantly in the arginine and glutamine groups at weeks 5 and 7 ( p  < 0.001), indicating better quality of life. Conclusions Both L-arginine and glutamine significantly reduced RIOM severity, pain, and weight loss compared to maltodextrin, while improving quality of life in patients with head and neck cancer. Although no statistically significant difference was found between the two, a higher proportion of patients receiving L-arginine achieved complete healing by week 7, suggesting a potential late advantage. These findings support the use of both amino acids as viable options for symptom management during radiotherapy. Trial registration ClinicalTrials.gov (NCT06764420), registered 08/01/2024.

Purpose To examine the dose–response effects of acute glutamine supplementation on markers of gastrointestinal (GI) permeability, damage and, secondary, subjective symptoms of GI discomfort in response to running in the heat. Methods Ten recreationally active males completed a total of four exercise trials; a placebo trial and three glutamine trials at 0.25, 0.5 and 0.9 g kg −1 of fat-free mass (FFM) consumed 2 h before exercise. Each exercise trial consisted of a 60-min treadmill run at 70% of V ˙ O 2max in an environmental chamber set at 30 °C. GI permeability was measured using ratio of lactulose to rhamnose (L:R) in serum. Plasma glutamine and intestinal fatty acid binding protein (I-FABP) concentrations were determined pre and post exercise. Subjective GI symptoms were assessed 45 min and 24 h post-exercise. Results Relative to placebo, L:R was likely lower following 0.25 g kg −1 (mean difference: − 0.023; ± 0.021) and 0.5 g kg −1 (− 0.019; ± 0.019) and very likely following 0.9 g kg − 1 (− 0.034; ± 0.024). GI symptoms were typically low and there was no effect of supplementation. Discussion Acute oral glutamine consumption attenuates GI permeability relative to placebo even at lower doses of 0.25 g kg −1 , although larger doses may be more effective. It remains unclear if this will lead to reductions in GI symptoms. Athletes competing in the heat may, therefore, benefit from acute glutamine supplementation prior to exercise in order to maintain gastrointestinal integrity.

AXA1125 and AXA1957 are novel, orally administered endogenous metabolic modulator compositions, specifically designed to simultaneously support multiple metabolic and fibroinflammatory pathways associated with nonalcoholic fatty liver disease (NAFLD). This study assessed safety, tolerability, and biologic activity of AXA1125 and AXA1957 in NAFLD. In this multicenter, 16-week, placebo-controlled, single-blind, randomized clinical study in subjects with NAFLD stratified by type 2 diabetes, AXA1125 24 g, AXA1957 13.5 g or 20.3 g, or placebo was administered twice daily. Key metabolism (MRI-proton density fat fraction [MRI-PDFF] and homeostasis model assessment of insulin resistance [HOMA-IR]) and fibroinflammation markers (alanine aminotransferase [ALT], corrected T1 [cT1], keratin-18 [K-18] M65, and N-terminal type III collagen propeptide [Pro-C3]) were evaluated. Safety outcomes included adverse events and standard laboratory assessments. Baseline characteristics of the 102 enrolled subjects, including 40 with type 2 diabetes, were consistent with presumed nonalcoholic steatohepatitis. AXA1125 showed consistently greater biologic activity than AXA1957 or placebo. Week 16 changes from baseline with AXA1125 vs placebo: MRI-PDFF -22.9% vs -5.7%, HOMA-IR -4.4 vs +0.7, ALT -21.9% vs -7.2%, K-18 M65 -13.6% vs +20.1%, cT1 -69.6 vs +18.3 ms (P < 0.05), and Pro-C3 -13.6% vs -3.6%. Week 16 changes from baseline with AXA1957 20.3 g: MRI-PDFF -8.1%, HOMA-IR +8.4, ALT -20.7%, K-18 M65 6.6%, cT1 -34.7 ms, and Pro-C3 -15.6%. A greater proportion of subjects treated with AXA1125 achieved clinically relevant thresholds: ≥30% MRI-PDFF, ≥17-IU/L ALT, and ≥80-ms cT1 reductions at week 16. Study products were safe and well tolerated with stable lipid and weight profiles. Both compositions showed multitargeted activity on relevant NAFLD pathways. AXA1125 demonstrated the greatest activity over 16 weeks, warranting continued clinical investigation in nonalcoholic steatohepatitis subjects.

To evaluate the safety and efficacy of L-glutamine in reducing vaso-occlusive crisis (VOC) and improving cerebral arterial blood flow in children with sickle cell disease (SCD). This is an interventional randomized controlled trial that recruited sixty SCD patients, aged 9.2 ± 3.7 years, who had at least two VOCs during the last 12 months and on a stable dose of hydroxyurea. They were randomly assigned in a 1:1 ratio to receive glutamine (0.3 gm/kg/dose/12h) orally for 24 weeks or the standard of care (SOC). All patients had VOCs in the last year > 3, those on glutamine had a higher number of VOCs and hospitalization for VOC in the last year. There was a decreasing trend in the number, severity, and hospitalization of VOC and a significantly lower cumulative number of VOCs and hospitalizations in the glutamine group than in SOC (p = 0.008, p < 0.001 respectively). Time-averaged mean maximum velocity for the glutamine group had a marginal increase in both middle cerebral arteries, all values remained normal within a normal range, and in both internal carotid arteries, values increased from abnormally low to normal ranges at week 24. Glutamine reduced the number of VOCs and severity and may have a potentially favorable impact on the cerebral arterial flow velocities.

Objective To investigate whether the application of L-glutamine (L-G) and hyaluronic acid (HA) associated with photobiomodulation (PBM) and the Preventive Oral Care Protocol (POCP) would present similar efficacy as the exclusive use of PBM, associated with POCP, in the prevention and control of severe oral mucositis (OM). Study design Patients with head and neck cancer undergoing radiochemotherapy (RCT) were randomized into two groups: group A, patients that received PBM + POCP ( n  = 24), and group B, patients that received PBM + POCP + L-G + HA ( n  = 24). OM was assessed using the National Cancer Institute (NCI) and World Health Organization (WHO) scales. The impact of oral health on patients’ quality of life and perception of OM symptoms was evaluated. Assessments were made at the 1st, 7th, 14th, 21st, and 30th radiotherapy (RT) sessions. Results When the severity of OM was assessed according to the WHO scale in the 30th RT, group B showed lower rates of severe OM than group A. There were no differences when using the NCI scale. The impact of oral health on quality of life and the symptoms reported by patients were lower in group B at all times evaluated. Conclusion The combination of PBM + POCP + L-G + HA resulted in a significantly lower severity of OM than PBM + POCP alone, according to the WHO scale at the 30th RT. Trial registration Brazilian Clinical Trials Registry—REBEC no. RBR-6ybmgcv. Registration March 27, 2022.

Background L‐glutamine and linoleic acid (LA) can suppress inflammatory cytokine expression; however, studies on their simultaneous application are limited due to polarity differences. Aims To investigate the effect of glutamine linoleate vesicles (QLAsomes) on skin sensitization by assessing their impact on sensitization‐related protein expression, bacterial growth, and clinical efficacy in relieving skin itchiness. Methods After synthesizing and analyzing QLAsomes, their inhibitory effects on capsaicin‐induced cytokine expression and Staphylococcus aureus growth were evaluated. In a double‐blind clinical trial, 24 participants (ages 22–63) with sensitized skin applied 10 wt% QLAsome cream on one side and a vehicle or no cream on the other twice daily for 2 weeks. Itchiness in the elbow area was assessed using a visual analog scale and expert evaluation. Skin barrier changes were measured using transepidermal water loss (TEWL), skin erythema, and stratum corneum (SC) hydration. Results QLAsomes, formed by L‐glutamine and LA through hydrogen bonding, were spherical vesicles (164.6 ± 3.1 nm). Based on the inhibitory effects of L‐glutamine and LA on inflammation‐related factors, QLAsomes inhibited the capsaicin‐induced expression of these factors more effectively than the individual components. IL‐4 inhibition was improved by over 26%. Matrix metalloproteinase‐1, which degrades collagen, showed 32% and 23% improvements compared to L‐glutamine and LA, respectively. In a clinical evaluation, 10 wt% QLAsome cream reduced itching by 45% compared to before application, which is a 67% improvement compared to placebo. Skin evaluations revealed improvements in erythema (12%), TEWL (15%), and SC hydration (19%), suggesting that QLAsomes enhance the skin barrier function. Conclusions QLAsomes showed up to 32% higher expression inhibition of key skin sensitization‐related factors than individual components, and based on this, improved pruritus by 67% more than placebo. As nanovesicles with skin‐soothing properties, they are effective for drug encapsulation and managing skin sensitivity in pharmaceutical and cosmetic industries.

In the present study, we aimed to investigate whether chronic oral glutamine (Gln) supplementation may alter metabolic parameters and the inflammatory profile in overweight and obese humans as well as whether Gln may modulate molecular pathways in key tissues linked to the insulin action in rats. Thirty-nine overweight/obese volunteers received 30 g of Gln or alanine (Ala-control) for 14 days. Body weight (BW), waist circumference (WC), hormones, and pro-inflammatory markers were evaluated. To investigate molecular mechanisms, Gln or Ala was given to Wistar rats on a high-fat diet (HFD), and metabolic parameters, euglycemic hyperinsulinemic clamp with tracers, and Western blot were done. Gln reduced WC and serum lipopolysaccharide (LPS) in overweight volunteers. In the obese group, Gln diminished WC and serum insulin. There was a positive correlation between the reduction on WC and LPS. In rats on HFD, Gln reduced adiposity, improved insulin action and signaling, and reversed both defects in glucose metabolism in the liver and muscle. Gln supplementation increased muscle glucose uptake and reversed the increased hepatic glucose production, in parallel with a reduced glucose uptake in adipose tissue. This insulin resistance in AT was accompanied by enhanced IRS1 O-linked-glycosamine association in this tissue, but not in the liver and muscle. These data suggest that Gln supplementation leads to insulin resistance specifically in adipose tissue via the hexosamine pathway and reduces adipose mass, which is associated with improvement in the systemic insulin action. Thus, further investigation with Gln supplementation should be performed for longer periods in humans before prescribing as a beneficial therapeutic approach for individuals who are overweight and obese.

The effects of two different dietary supplements on the redox status of healthy human participants were evaluated. The first supplement (GluS, Glutathione Synthesis) contains the precursors for the endogenous synthesis of glutathione and the second (GluReS, Glutathione and Resveratrol Synthesis) contains in addition polydatin, a precursor of resveratrol. To assess the influence of GluS and GluReS on the redox status, ten thiol species and three vitamins were measured before (t0) and after 8 weeks (t1) of dietary supplementation. An inflammatory marker, neopterin, was also assessed at the same time points. Both supplements were highly effective in improving the redox status by significantly increasing the reduced-glutathione (GSH) content and other reduced thiol species while significantly decreasing the oxidized species. The positive outcome of the redox status was most significant in the GluRes treatment group which also experienced a significant reduction in neopterin levels. Of note, the endogenous levels of vitamins C, E and A were significantly increased in both treatment groups, with best results in the GluReS group. While both dietary supplements significantly contributed to recognized antioxidant and anti-inflammatory outcomes, the effects of GluReS, the combination of glutathione and resveratrol precursors, were more pronounced. Thus, dietary supplementation with GluReS may represent a valuable strategy for maintaining a competent immune status and a healthy lifespan.

Objective To assess the efficacy of glutamine mouthwash versus standard oral hygiene protocol (SOHP) in reducing the overall incidence, duration and severity of oral mucositis in children with acute lymphoblastic leukemia (ALL) receiving High Dose Methotrexate (HDMTX). Methods In this cross-over trial, children with ALL due to receive four courses of HDMTX (2 g/m 2 /dose) (on days 8, 22, 36, and 50 of consolidation) were randomized to receive two consecutive courses of HDMTX with glutamine mouthwash plus SOHP, followed by two HDMTX courses with SOHP only; or vice-versa. Glutamine suspension was administered twice daily by swish and swallow technique, starting one day before the course of HDMTX and continued upto 7 days or till mucositis persisted. SOHP comprised supervised brushing, chlorhexidine mouthwash, and clotrimazole mouth-paint. Severity of mucositis was graded using WHO grading and pain was assessed by Wong-Baker FACES Pain Rating Scale. Results Sixty four courses of HDMTX were analyzed. The overall incidence of mucositis in the glutamine group was comparable to the SOHP group (71.8% vs 81.2%; P  = 0.08). The glutamine group had a significantly lesser incidence of severe mucositis [3.1% vs 44%; RR (95% CI) 0.07 (0.01, 0.35); P  < 0.001], shorter overall duration of mucositis [2 (0, 3) days vs 5 (3, 5) days, P  < 0.001] and lower median (IQR) pain scores [4.5 (0, 6) Vs 8 (5.25, 8), P  < 0.001]. Conclusion Glutamine mouthwash is effective in reducing the incidence of severe mucositis and overall duration of mucositis and associated pain in children receiving HDMTX.