Oral Glutamine Research Articles

Clinical and biochemical assessment of the effect of glutamine in management of radiation induced oral mucositis in patients with head and neck cancer: Randomized controlled clinical trial

BackgroundThis study aimed to evaluate the effect of oral glutamine suspension on salivary levels of transforming growth factor beta 1 (TGF-β1), a cytokine involved in inflammation and Tumor progression, and the severity of radiation-induced oral mucositis (RIOM) in head and neck cancer patients. This is the first study to investigate the impact of glutamine on TGF-β1 levels in head and neck cancer patients with radiation induced oral mucositis (RIOM). MethodsIn this randomized controlled clinical trial, 50 HNC patients were enrolled and received either glutamine oral suspension or maltodextrin as a placebo from the baseline of RIOM to the end of radiotherapy. Salivary TGF-β1 levels were measured at baseline and after treatment. Also, RIOM was assessed using the World Health Organization (WHO) Oral Toxicity Scale, the Oral Mucositis Assessment Scale (OMAS), the Pain Visual Analog Scale (Pain-VAS), the incidence of opioid use, and body mass index (BMI). ResultsGlutamine significantly reduced salivary TGF-β1 levels and improved RIOM symptoms, such as pain, opioid use, and weight loss. The reduction of TGF-β1 levels was associated with the improvement of RIOM severity. ConclusionGlutamine may modulate the inflammatory response and enhance wound healing in RIOM by decreasing salivary TGF-β1 levels. These findings support the use of glutamine as a potential intervention for RIOM and nutritional support for improving radiation sensitivity. Trial RegistrationThis study was registered on clinicalTrials.gov with identifier no. NCT05856188.

Oral glutamine: Is there a role in the amelioration of radiation-induced mucositis? A prospective case-control study at a tertiary care centre in North India.

The most frequently occurring painful and dose-limiting side effect of radiation therapy (RT) to the head and neck region is oral mucositis (OM). Several studies demonstrated that glutamine may reduce the severity and the duration of OM significantly during RT and chemo-radiotherapy in patients with head and neck cancer (HNC). Between January 2021 and August 2022, a prospective single institutional case-control study compared the efficacy and safety of oral glutamine on radiation-induced mucositis in patients with HNC. Of 60 biopsy-proven patients with HNC, 30 patients in the study arm received oral glutamine suspension (10 g in 500 mL of water) orally once daily, 2 hours before RT, receiving definitive or adjuvant RT and chemo-radiotherapy, while as 30 patients in the control arm received placebo with the same dose and schedule (n = 30 in the study arm and n = 30 in the control arm). A total of 27 (90%) in the glutamine arm and 28 (93.33%) patients in the control arm developed mucositis. Grade 3 mucositis (13.33%) and Grade 4 mucositis (6.66%), respectively, were significantly less ( P = .040 and P = .004) in the glutamine arm. The mean duration of grade 3 and grade 4 mucositis was significantly less in the glutamine arm (8.94 days in the study arm vs. 14.54 in the control arm; P = .0001). The mean time of onset of OM was significantly delayed in the glutamine arm in comparison to the control arm with P < .001. Glutamine delays the onset of OM and decreases the severity of OM in patients of HNC receiving RT with or without chemotherapy.

Acute and persistent effects of oral glutamine supplementation on growth, cellular proliferation, and tight junction protein transcript abundance in jejunal tissue of low and normal birthweight pre-weaning piglets.

Breeding for higher fertility has resulted in a higher number of low birthweight (LBW) piglets. It has been shown that LBW piglets grow slower than normal birthweight (NBW) littermates. Differences in growth performance have been associated with impaired small intestinal development. In suckling and weaning piglets, glutamine (Gln) supplementation has been associated with improved growth and intestinal development. This study was designed to examine the effects of oral Gln supplementation on growth and small intestinal parameters in LBW and NBW suckling piglets. At birth (day 0), a total of 72 LBW (1.10 ± 0.06 kg) and 72 NBW (1.51 ± 0.06) male piglets were selected. At day 1, litters were standardized to 12 piglets, and experimental piglets supplemented daily with either Gln (1 g/kg BW) or isonitrogenous amounts of Alanine (Ala) as control (1.22 g/kg BW) until day 12. Creep feed was offered from day 14 onward. Subgroups of piglets were euthanized at days 5, 12, and 26 for the analyses of jejunal morphometry, cellular proliferation, glutathione concentration and transcript abundance of tight junction proteins. From age day 11 to 21, Gln supplemented LBW (LBW-Gln) piglets were heavier than Ala supplemented LBW (LBW-Ala) littermates (P = 0.034), while NBW piglets were heavier until age day 26 compared to LBW littermates. Villus height was higher in LBW-Gln compared to LBW-Ala on age day 12 (P = 0.031). Sporadic differences among supplementation and birthweight groups were detected for jejunal cellular proliferation, cellular population and glutathione concentration, whereas age was the most dominant factor. These results show that Gln supplementation improved the growth of LBW piglets compared to LBW-Ala beyond the termination of Gln supplementation, but this was not associated with consistent effects on selected parameters of jejunal development.

Tolerability of glutamine supplementation in older adults: a double-blind placebo-controlled randomized clinical trial.

In this double-blind placebo-controlled randomized investigation, we assessed the tolerability of glutamine in older adults recruited from three daycare centers. The relevance of studying glutamine supplementation in elderly patients lies in its potential to provide a well-tolerated intervention. Glutamine, a crucial amino acid, plays a vital role in various physiological processes, including immune function and protein synthesis. Understanding its impact on older adults is essential, given the potential implications for their health and well-being. Participants received a daily dose of 12.4 g of oral effervescent glutamine (EGln group) or maltodextrin (placebo group) for 60 days. Fifteen patients from each group completed the study. The mean ages were 77.0±9.1 and 79.0±6.9 years for the EGln and placebo groups, respectively. We evaluated body mass index, aminogram, hemogram, plasma levels of glucose, prealbumin, albumin, urea, creatinine, uric acid, C-reactive protein, vitamin D, calcium, sodium, potassium, and the plasma activities of aspartate aminotransferase and alanine aminotransferase. Notably, we quantified a broad array of inflammatory markers and growth factors providing a holistic understanding of the potential effects of glutamine supplementation. The results demonstrated that oral glutamine did not induce significant changes in any evaluated parameters, and no adverse effects were reported. This finding suggested that the dosage of glutamine used in this study was well-tolerated and safe. This information contributes to the broader understanding of glutamine supplementation, emphasizing its safety and supporting its potential as a viable intervention for maintaining health in aging individuals.

Oral glutamine dipeptide or oral glutamine free amino acid reduces burned injury progression in rats.

This study was carried out to evaluate the effect of Glutamine, as a dipeptide or a free amino acid form, on the progression of burn injuries in rats. Thirty male Wistar rats were burned with a comb metal plate heated in boiling water (98 °C) for three minutes, creating four rectangular full-thickness burn areas separated by three unburned interspaces (zone of stasis) in both dorsum sides. The animals were randomized into three groups (n=10): saline solution (G1-Control) and treated groups that orally received Glutamine as dipeptide (G2-Dip) or free amino acid (G3-FreeAA). Two and seven days after burn injury, lesions were photographed for unburned interspaces necrosis evolution assessment. Seven days after injury, glutathione seric was measured and histopathological analysis was performed. By photographs, there was a significant reduction in necrosis progression in G3-Free-AA between days two and seven. Histopathological analysis at day 7 showed a significantly higher stasis zone without necrosis and a higher number of fibroblasts in G2-Dip and G3-FreeAA compared with G1-Control. Also, glutathione serum dosage was higher in G2-Dip. The plasmatic glutathione levels were higher in the G2-Dip than the G1-Control, and there was a trend to higher levels in G3-FreeAA. The reduction in histological lesions, greater production of fibroblasts, and greater amounts of glutathione may have benefited the evolution of burn necrosis, which showed greater preservation of interspaces.

Oral glutamine supplementation relieves muscle loss in immobilized rats, altering p38MAPK and FOXO3a signaling pathways

BackgroundSkeletal muscle synthesizes, stores, and releases body L-glutamine (GLN). Muscle atrophy due to disabling diseases triggers the activation of proteolytic and pro-apoptotic cell signaling, thus impairing the body's capacity to manage GLN content. This situation has a poor therapeutic prognosis. ObjectiveEvaluating if oral GLN supplementation can attenuate muscle wasting mediated by elevated plasma cortisol and activation of caspase-3, p38MAPK, and FOXO3a signaling pathways in soleus and gastrocnemius muscles of rats submitted to 14-day bilateral hindlimbs immobilization. MethodsAnimals were randomly distributed into six groups: non-immobilized rats (Control), control orally supplemented with GLN (1 g kg−1) in solution with L-alanine (ALA: 0.61 g kg−1; GLN+ALA), control orally supplemented with dipeptide L-alanyl-L-glutamine (DIP; 1.49 g kg−1), hindlimbs immobilized rats (IMOB), IMOB orally GLN+ALA supplemented (GLN+ALA-IMOB), and IMOB orally DIP supplemented (DIP-IMOB). Plasma and muscle GLN concentration, plasma cortisol level, muscle caspase-3 activity, muscle p38MAPK and FOXO3a protein content (total and phosphorylated forms), and muscle cross-sectional area (CSA) were measured. ResultsCompared to controls, IMOB rats presented: a) increased plasma cortisol levels; b) decreased plasma and muscle GLN concentration; c) increased muscle caspase-3 activity; d) increased total and phosphorylated p38MAPK protein content; e) increased FOXO3a and decreased phosphorylated FOXO3a protein content; f) reduced muscle weight and CSA befitting to atrophy. Oral supplementation with GLN+ALA and DIP was able to significantly attenuate these effects. ConclusionsThese findings attest that oral GLN supplementation in GLN+ALA solution or DIP forms attenuates rats' skeletal muscle mass wasting caused by disuse-mediated muscle atrophy.

Preoperative Glutamine Supplementation in Gastric Cancer—Thrombocyte Phagocytic Activity and Early Postoperative Outcomes

Background: The aim of this study was to determine the phagocytic activity of thrombocytes in patients with gastric cancer and to assess the effect of oral and parenteral preoperative glutamine-based immunonutrition on nutritional status, thrombocyte phagocytic activity, and early postoperative outcomes. Methods: Patients suffering from invasive gastric cancer had been treated with preoperative immunonutrition with glutamine, and they were compared to patients without nutritional treatment. Nutritional status, percentage of weight loss, and BMI were assessed. Levels of total protein, albumin, cholesterol, triglycerides, platelets, and their phagocytic ability were measured twice. Postsurgical complications were assessed via the Clavien–Dindo classification. Results: Group I consisted of 20 patients with an oral glutamine—10 g daily. Group II had 38 patients who received intravenous glutamine, 1.5 mL per kg body weight of Dipeptiven. Group III consisted of 25 patients who did not receive preoperative immunonutrition. In total, 47% of patients in Group I, 54% of patients in Group II, and 33% of patients in Group III were malnourished. In Group I, the percentage of phagocytizing platelet (%PhP) was 1.1 preoperatively and 1.2 postoperatively. The phagocytic index (PhI) was 1.0 and 1.1. In Group II, %PhP was 1.1 and 1.2 and PhI was 1.0 and 1.1. In Group III, the %PhP was 1.0 and 1.2 and PhI was 1.0 and 1.1. An increase in triglyceride level was observed in both immunonutrition groups. There was a decline in total protein and albumin level in Group II. In Group III, there was a decline in total protein, albumin, and cholesterol level. The total platelet count and PhI were increased in both immunonutrition groups. There was also a rise in %PhP in Group II. In Group III, there was a rise in blood platelet level, %PhP, and PhI. The complication rates were 53% in Group I, 29% in Group II, and 40% in Group III. Conclusions: In invasive gastric cancer, laboratory nutritional parameters are significantly reduced, causing malnutrition in 44.7% of patients. Oral glutamine supplementation inhibited the postoperative decline in protein metabolism parameters; however, this did not affect the reduction in the percentage of postoperative complications. Glutamine used preoperatively significantly reduced the percentage of serious surgical complications, regardless of the way it was supplemented. Patients with invasive gastric cancer have a significant decrease in platelet phagocytic activity. The administered preoperative parenteral nutrition and the surgical procedure itself influenced the improvement of the phagocytic activity of blood platelets. Glutamine did not have this effect, regardless of the route of administration.

Effect of glutamine supplementation in elderly people with emphasis on sarcopenia, immunity and hypertrophy: a concise systematic review

Currently, the aging of the population is no longer a forgotten subject for health professionals in Brazil. This is due to the decrease in the birth rate in the country and the improvement in quality of life, this first factor was boosted after the ease of access to information on contraceptive methods and their distribution by the health system. As a result, the Nutrition area has been studying more diligently ways to provide elderly people with methods that contribute to a more comfortable, healthy, and long-lasting life. The nutritionist is essential to identify the deficits and disharmonization of the body of the elderly caused naturally over the years in people's lives, such as loss of muscle mass, and lack of nutrients, among others. Given this scenario, this work will be focused on showing that the use of oral Glutamine supplementation contributes to the gain of muscle mass in the elderly since this natural amino acid present mainly in the muscle tissue of the human body is greatly reduced due to loss of mass skin and body weight gain caused by the slow metabolism found in older people. In this way, supplementation along with a well-designed nutritional table and an exercise routine will promote less chance of injury to the elderly due to a lack of nutrients and greater physical resistance. To reinforce and prove this study, we will use the literature review method distributed in topics.

Hydrolyzed whey protein enriched with glutamine dipeptide attenuates skeletal muscle damage and improves physical exhaustion test performance in triathletes.

To investigate the effects of hydrolyzed whey protein enriched with glutamine dipeptide on the percentage of oxygen consumption, second ventilatory threshold, duration and total distance covered, and skeletal muscle damage during an exhaustion test in elite triathletes. The study was a randomized, double-blinded, placebo-controlled, crossover trial. Nine male triathletes performed a progressive incremental test on a treadmill ergometer (1.4 km h-1·3 min-1) 30 min after ingesting either 50 g of maltodextrin plus four tablets of 700 mg hydrolyzed whey protein enriched with 175 mg of glutamine dipeptide diluted in 250 ml of water (MGln) or four tablets of 700 mg maltodextrin plus 50 g maltodextrin diluted in 250 ml of water (M). Each athlete was submitted to the two dietary treatments and two corresponding exhaustive physical tests with an interval of one week between the interventions. The effects of the two treatments were then compared within the same athlete. Maximal oxygen consumption, percentage of maximal oxygen consumption, second ventilatory threshold, and duration and total distance covered were measured during the exhaustion test. Blood was collected before and immediately after the test for the determination of plasma lactate dehydrogenase (LDH) and creatine kinase (CK) activities and lactate concentration (also measured 6, 10, and 15 min after the test). Plasma cytokines (IL-6, IL-1β, TNF-α, IL-8, IL-10, and IL-1ra) and C-reactive protein levels were also measured. A single dose of MGln increased the percentage of maximal oxygen consumption, second ventilatory threshold duration, and total distance covered during the exhaustion test and augmented plasma lactate levels 6 and 15 min after the test. MGln also decreased plasma LDH and CK activities indicating muscle damage protection. Plasma cytokine and C-reactive protein levels did not change across the study periods. Conditions including overnight fasting and a single dose of MGln supplementation resulted in exercising at a higher percentage of maximal oxygen consumption, a higher second ventilatory threshold, blood lactate levels, and reductions in plasma markers of muscle damage during an exhaustion test in elite triathletes. These findings support oral glutamine supplementation's efficacy in triathletes, but further studies require.

Evaluation of Dosage and Food Effect on L-Glutamine Exposure for Sickle Cell Anemia: A Population Pharmacokinetic Analysis

Introduction: L-glutamine (Endari®) is an amino acid approved for the treatment of sickle cell disease (SCD). The mechanism of action of L-glutamine in SCD is not fully understood but believed to involve, at least partly, augmentation of the de novo synthesis of intracellular glutathione, which can protect sickle erythrocytes from oxidant injury. As an endogenous compound, the pharmacokinetics (PK) of L-glutamine have not been extensively studied, and currently recommended dosing is based on single-dose studies. It is also unclear how physiology, food intake, and dose impact L-glutamine drug exposure in patients with SCD. Our objective was to understand the PK of multiple dose L-glutamine therapy using a population PK analysis to identify factors that may inform optimal dosing of L-glutamine in children and adults with SCD. Methods: A total of 400 L-glutamine plasma concentration-time data points collected from 12 participants (NCT04684381) were available for population PK analysis. Each participant received 3 ascending oral doses (0.1 and 0.3 g/kg given BID and 0.6 g/kg given once daily) during a four-week study. Plasma L-glutamine and other amino acid levels were obtained before and after oral L-glutamine doses at each visit and quantified by ion exchange chromatography. Population PK analysis was performed using nonlinear mixed effect modeling by NONMEM 7.4 (ICON, Ellicott City, MD, USA). Multiple base model structures including one-compartment and two-compartment models were explored to describe the L-glutamine PK. In addition to the primary PK parameters clearance (CL/F) and volume of distribution (V/F), a relative bioavailability (F) was included in the modeling to account for the potential impact of dose and food on L-glutamine PK. Patient demographics and laboratory data, including body weight, body surface area, age, serum creatinine levels, urine creatinine levels, baseline glutamine level, meal intake, and dosages were evaluated as potential covariates using the stepwise selection method. The change in the objective function value (OFV) between two nested models was assumed to follow the χ2 distribution and was tested at a significance level of <0.01 (-6.64 points in OFV). The final model was evaluated by goodness-of-fit (GOF) plots and visual predictive check (VPC) analysis. For the VPC analysis, one thousand replicates of simulated datasets were generated using the final model, and the distribution of simulated observations was compared with the actual observations. Results: A one-compartment with first-order absorption model best described the oral dose L-glutamine concentration-time profiles. The data did not support the inclusion of a lag time in drug absorption, which is consistent with the observed rapid absorption. In accordance with allometric theory, body size was found to be significantly correlated with glutamine oral clearance (CL/F; where F represents bioavailability, which is not measured and therefore unknown) and volume of distribution (V/F). We therefore used allometrically scaled body weight to account for differences in body size. Dose-normalized peak concentration (Cmax) decreased with dose escalation (Figure 1), indicating capacity-limited, non-linear PK of oral L-glutamine. Covariate analysis identified that baseline glutamine levels and dosages negatively correlated with glutamine clearance, whereas food intake did not significantly impact glutamine clearance. Higher doses decreased the relative bioavailability of oral glutamine, again indicating a non-linear saturable absorption. Model evaluation indicated no systemic bias (Figure 2). The estimates of L-glutamine oral clearance and volume of distribution were 66 L/h/70 kg and 140 L/70 kg, respectively. Conclusions: This is the first report of a population PK analysis of L-glutamine in patients with SCD. We identified that higher baseline glutamine levels and higher doses were associated with lower L-glutamine clearance. In addition, increased doses reduced relative bioavailability, indicating that higher doses (>0.3 g/kg) may not provide higher drug concentrations. Food intake did not have a significant influence on glutamine clearance, implying that L-glutamine can be taken with or without food. Our findings will help to inform optimized dosing of L-glutamine for patients with SCD and potentially permit individualized PK-guided dosing to maximize treatment benefits. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

ORAL GLUTAMINE SUPPLEMENTATION FOR REFRACTORY ECZEMA AND ERYTHRODERMA WITH A HYPER-IGE PHENOTYPE

<h3>Introduction</h3> Severe eczema is managed with ceramide-containing emollients, topical glucocorticoids, dupilumab and/or JAK inhibitors. However, targeted treatments may not be readily available. Glutamine is a safe, inexpensive, over-the-counter oral amino acid that could aid eczema control. <h3>Case Description</h3> A 5-year-old, previously healthy female presented with diffuse erythroderma (Figure 1). Rashes appeared 4 months prior, associated with pruritus. She had inadequate relief despite moisturization, topical and oral glucocorticoids. On exam, she had diffuse erythroderma (40% BSA) and bilateral supraclavicular and axillary lymphadenopathy. Serum IgE was significantly elevated - 45,850 IU/mL (ref. ≤ 90 IU/mL), she had increased eosinophils (1.69k/uL [0-0.8k/uL) and total CD4+ and memory (CD4+CD45RO+) T cells (1153 cells/uL [100-510cells/uL). Due to lymphadenopathy and family history of childhood leukemia in maternal aunt, she had a T-cell clonality assay by PCR which was unremarkable. Targeted primary immunodeficiency genetics panel (obtained for her hyper-IgE phenotype) was negative for pathogenic variants. Skin biopsy showed spongiotic dermatitis with staphylococcal impetiginization. She was treated with 10 days of oral cephalexin without significant improvement. She started oral glutamine 5g daily with continued skin moisturization. Two months later, she had only mild erythema of the shins, with decreased IgE 30,982 IU/mL and resolution of adenopathy. <h3>Discussion</h3> The patient had a hyper-IgE phenotype, raising concern for a primary atopic disorder. She achieved sustained improvement with glutamine supplementation. Previous studies reported improvement with glutamine among patients with eczema and heterozygous dominant-negative CARD11 mutations and decreased eczema risk in infants receiving early glutamine.

Amino acids for the prevention of mortality and morbidity in preterm infants: a systematic review and network meta-analysis

To determine the effectiveness and safety of amino acids in preventing the mortality and morbidity among preterm infants. We conducted a systematic review and network meta-analysis. We searched MEDLINE, EMBASE, Web of Science, CINAHL, Scopus, Cochrane, and Google Scholar, and grey literature, from databases inception to January 2021. We included randomized trials that evaluated any amino acids on preterm or low-birth weight infants. We performed frequentist pairwise and network meta-analyses and used the GRADE methodology to assess the certainty of the evidence and provide a summary of the results.We included 18 trials (3702 infants). Low certainty evidence showed that there seems to be no benefit for arginine, glutamine, or N-acetylcysteine in reducing all-cause mortality. Oral arginine likely results in reduction of necrotizin enterocolitis (NEC) stage ≥ II (OR 0.48; 95% CI 0.26–0.90; moderate certainty). Oral glutamine may reduce the likelihood of developing late-onset sepsis (LOS) compared to placebo (OR 0.62; 95% CI 0.47–0.82; low certainty); and likely reduces time to reach full enteral feeding (MD = − 2.63 days; 95% CI − 4.99 to − 0.27; moderate certainty). Amino acids may have no effect on mortality. Oral arginine may reduce severe NEC, and oral glutamine may reduce LOS and the time to reach full feeding.Systematic review registration: PROSPERO registration number: CRD4201603873.

Effects of Oral Glutamine Supplementation, Birthweight and Age on Colonic Morphology and Microbiome Development in Male Suckling Piglets.

Mortality, impaired development and metabolic dysfunctions of suckling low-birthweight piglets may be influenced by modulating the intestinal microbiome through glutamine supplementation. Therefore, this study examined whether glutamine supplementation may affect the colonic development and microbiome composition of male low- and normal-birthweight piglets at 5 and 12 days of age. Suckling piglets were supplemented orally with glutamine or alanine. Colonic digesta samples were obtained for 16S rDNA sequencing, determination of bacterial metabolites and histomorphological tissue analyses. Glutamine-supplemented piglets had lower concentrations of cadaverine and spermidine in the colonic digesta (p < 0.05) and a higher number of CD3+ colonic intraepithelial lymphocytes compared to alanine-supplemented piglets (p < 0.05). Low-birthweight piglets were characterised by a lower relative abundance of Firmicutes, the genera Negativibacillus and Faecalibacterium and a higher abundance of Alistipes (p < 0.05). Concentrations of cadaverine and total biogenic amines (p < 0.05) and CD3+ intraepithelial lymphocytes (p < 0.05) were lower in low- compared with normal-birthweight piglets. In comparison to the factor age, glutamine supplementation and birthweight were associated with minor changes in microbial and histological characteristics of the colon, indicating that ontogenetic factors play a more important role in intestinal development.

A validated UPLC-MS/MS method for quantification of glutamine in plasma and pharmacokinetic study of oral glutamine tablets in healthy Beagles.

This study aimed to clarify the laws of glutamine tablets absorption, distribution, and metabolism in Beagles and to provide a basis for formulating dosing regimens. Twelve healthy Beagles were enrolled the absolute bioavailability study with a crossover design . Glutamine tablets (240 mg/kg b.w.) or glutamine sterile solution (60 mg/kg b.w.) were administered. A method for the determination of glutamine in Beagles' plasma by UPLC-MS/MS was established, with high sensitivity, specificity, and simplicity. Based on the study of endogenous glutamine concentration, the mean concentration of the four time points before drug administration was selected as the background concentration of glutamine. Pharmacokinetic parameters were calculated by non-compartment model. The Cmax of glutamine was 136.11 ± 72.51 μg/ml, Tmax was 0.85 ± 0.29 h, and t1/2λz was 0.42 ± 0.27 h after oral administration. The AUC0-t of glutamine was 116.30 ± 75.15 h·μg/ml vs. 44.55 ± 22.48 h·μg/ml following oral and IV administration, respectively, with an absolute bioavailability of 64.74% ± 19.18%. The results showed glutamine was quickly absorbed and eliminated in Beagles with high bioavailability. Therefore, glutamine is suitable to be prepared as oral tablets and recommended to shorten the dosing interval.

P130. Bacterial metabolites in stomach and jejunum of neonatal piglets and the influence of oral glutamine supplementation on them

P130. Bacterial metabolites in stomach and jejunum of neonatal piglets and the influence of oral glutamine supplementation on them

Effects of oral glutamine supplementation on jejunal morphology, development, and amino acid profiles in male low birth weight suckling piglets.

BackgroundIt has been shown that small intestine development in low birth weight (LBW) piglets is impaired. Glutamine (Gln) has been reported to improve piglet health and intestinal function in weaned piglets, but data is scarce in suckling piglets. This study was conducted to investigate the effects of oral Gln supplementation compared to Alanine (Ala) on jejunal development and function in 5 and 12 d old male LBW and normal birth weight (NBW) suckling piglets.ResultsGln had no effect on the jejunal morphology, development, tissue and digesta amino acid profiles and mRNA abundance of genes involved in amino acid transport, metabolism, glutathione synthesis in LBW piglets when compared to Ala supplementation and birth weight controls at 5 and 12 d. Only the concentration of Gln in jejunal tissue was higher in NBW piglets supplemented with Gln compared to Ala at 5 d (P < 0.05). A comparison of the birth weight groups showed no differences between LBW and NBW piglets at 5 and 12 d in any parameter. Jejunal crypt depth, villus height / width, tunica muscularis thickness, number of goblet and IgA positive cells, the ratio of jejunal RNA to DNA and the concentration of DNA, protein and RNA changed (P < 0.05) from 5 compared to 12 d. The concentrations of several free, and protein bound amino acids as well as amino metabolites differed between age groups in jejunal tissue but the digesta concentrations were affected to a lesser extent.ConclusionsOral Gln supplementation to suckling male piglets over the first 12 d of life was not associated with changes in jejunal parameters measured in this study. The absence of effects may indicate that Gln is absorbed as well as metabolized in the upper intestinal tract and thus could benefit intestinal development at a more proximal location.

Ca2+-Permeable Channels/Ca2+ Signaling in the Regulation of Ileal Na+/Gln Co-Transport in Mice.

Oral glutamine (Gln) has been widely used in gastrointestinal (GI) clinical practice, but it is unclear if Ca2+ regulates intestinal Gln transport, although both of them are essential nutrients for mammals. Chambers were used to determine Gln (25 mM)-induced I sc through Na+/Gln co-transporters in the small intestine in the absence or the presence of selective activators or blockers of ion channels and transporters. Luminal but not serosal application of Gln induced marked intestinal I sc , especially in the distal ileum. Lowering luminal Na+ almost abolished the Gln-induced ileal I sc , in which the calcium-sensitive receptor (CaSR) activation were not involved. Ca2+ removal from both luminal and serosal sides of the ileum significantly reduced Gln- I sc . Blocking either luminal Ca2+ entry via the voltage-gated calcium channels (VGCC) or endoplasmic reticulum (ER) release via inositol 1,4,5-triphosphate receptor (IP3R) and ryanodine receptor (RyR) attenuated the Gln-induced ileal I sc , Likewise, blocking serosal Ca2+ entry via the store-operated Ca2+ entry (SOCE), TRPV1/2 channels, and Na+/Ca2+ exchangers (NCX) attenuated the Gln-induced ileal I sc . In contrast, activating TRPV1/2 channels enhanced the Gln-induced ileal I sc . We concluded that Ca2+ signaling is critical for intestinal Gln transport, and multiple plasma membrane Ca2+-permeable channels and transporters play roles in this process. The Ca2+ regulation of ileal Na+/Gln transport expands our understanding of intestinal nutrient uptake and may be significant in GI health and disease.

Effects of oral cystine and glutamine on exercise-induced changes in gastrointestinal permeability and damage markers in young men

PurposeAlthough acute prolonged strenuous exercise has been shown to increase markers of gastrointestinal permeability and damage, little is known regarding the efficacy of nutritional supplement interventions on the attenuation of exercise-induced gastrointestinal syndrome. This study addressed the effects of oral amino acid supplementation on markers of gastrointestinal permeability and damage in response to exercise.MethodsSixteen active men aged 22.7 ± 2.6 years (mean ± standard deviation) completed placebo or cystine and glutamine supplementation trials in random order. Participants received either a placebo or cystine and glutamine supplements, three times a day for 5 days, separated by a 2-week washout period. On day 6, participants took their designated supplements 30 min before running at a speed corresponding to 75% of maximal oxygen uptake for 1 h, followed by a 4-h rest period. Blood samples were collected pre-exercise, immediately post-exercise, 30 min post-exercise, and 1, 2 and 4 h post-exercise on day 6. The plasma lactulose to mannitol ratio (L:M) and plasma intestinal fatty acid-binding protein (I-FABP) were used as markers of gastrointestinal permeability and damage, respectively.ResultsPlasma L:M (linear mixed model, coefficient ± standard error: − 0.011 ± 0.004, P = 0.0090) and changes (i.e., from pre-exercise) in plasma I-FABP (linear mixed model, − 195.3 ± 65.7 coefficient ± standard error (pg/mL), P = 0.0035) were lower in the cystine and glutamine supplementation trial than in the placebo trial.ConclusionOral cystine and glutamine supplementation attenuated the markers of gastrointestinal permeability and damage after 1 h of strenuous running in young men.Trial registration numberUMIN000026008.Date of registration13 December 2018.

Implications for the metabolic fate of oral glutamine supplementation within plasma and erythrocytes of patients with sickle cell disease: A pharmacokinetics study

ObjectivesL-Glutamine is FDA-approved for sickle cell disease (SCD), yet the mechanism(s)-of-action are poorly understood. We performed a pharmacokinetics (pK) study to determine the metabolic fate of glutamine supplementation on plasma and erythrocyte amino acids in patients with SCD. DesignA pK study was performed where patients with SCD fasting for > 8 h received oral L-glutamine (10 g). Blood was analyzed at baseline, 30/60/90 min/2/3/4/8 hrs. A standardized diet was administered to all participants at 3 established time-points (after 2/5/7hrs). A subset of patients also had pK studies performed without glutamine supplementation to follow normal diurnal fluctuations in amino acids. SettingComprehensive SCD Center in Oakland, California ResultsFive patients with SCD were included, three of whom performed pK studies both with and without glutamine supplementation. Average age was 50.6 ± 5.6 years, 60% were female, 40% SS, 60% SC. Plasma glutamine levels increased significantly after oral glutamine supplementation, compared to minimal fluctuations with diet. Plasma glutamine concentration peaked within 30-min of ingestion (p = 0.01) before decreasing to a plateau by 2-h that remained higher than baseline by 8 h. Oral glutamine also increased plasma arginine concentration, which peaked by 4-h (p = 0.03) and remained elevated through 8-h. Erythrocyte glutamine levels began to increase by 8-h, while erythrocyte arginine concentration peaked at 4-h. ConclusionsOral glutamine supplementation acutely improved glutamine and arginine bioavailability in both plasma and erythrocytes. This is the first study to demonstrate that glutamine therapy increases arginine bioavailability and may provide insight into shared mechanisms-of-action between these conditionally-essential amino acids.

No protective benefits of low dose acute L-glutamine supplementation on small intestinal permeability, epithelial injury and bacterial translocation biomarkers in response to subclinical exertional-heat stress: A randomized cross-over trial

ABSTRACT Exertional heat stress disrupts gastrointestinal permeability and, through subsequent bacterial translocation, can result in potentially fatal exertional heat stroke. Glutamine supplementation is a potential countermeasure although previously validated doses are not universally well tolerated. Ten males completed two 80-minute subclinical exertional heat stress tests (EHSTs) following either glutamine (0.3 g kg FFM−1) or placebo supplementation. Small intestinal permeability was assessed using the lactulose/rhamnose dual sugar absorption test and small intestinal epithelial injury using Intestinal Fatty-Acid Binding Protein (I-FABP). Bacterial translocation was assessed using the total 16S bacterial DNA and Bacteroides/total 16S DNA ratio. The glutamine bolus was well tolerated, with no participants reporting symptoms of gastrointestinal intolerance. Small intestinal permeability was not influenced by glutamine supplementation (p = 0.06) although a medium effect size favoring the placebo trial was observed (d = 0.73). Both small intestinal epithelial injury (p < 0.01) and Bacteroides/total 16S DNA (p = 0.04) increased following exertional heat stress, but were uninfluenced by glutamine supplementation. Low-dose acute oral glutamine supplementation does not protect gastrointestinal injury, permeability, or bacterial translocation in response to subclinical exertional heat stress.