Effects Of Glutamine Supplementation Research Articles

Effects Of Glutamine Supplementation On Overload-induced Muscle Growth And Function In Mice

Muscle hypertrophy induced by functional overload (FO) provides an in vivo model to study muscle growth. Glutamine has been shown to improve muscle function, maintain contractile protein levels, and reduce inflammation; however, its effects during muscle growth is unclear. PURPOSE: These experiments tested the hypothesis that glutamine supplementation positively impacts the skeletal muscle response to a growth stimulus as evidenced by greater hypertrophy, increased growth factor levels, and improved contractile function compared to placebo. METHODS: Mice underwent FO of the plantaris or sham surgery. In vivo plantaris force and fatigue resistance (% of maximal force after 10 contractions) were measured 14 days after FO or sham in mice receiving daily glutamine (1 g/kg body mass) or placebo (n= 7-9/group). Insulin-like growth factor 1 (IGF-1) was measured in the plantaris by ELISA after 14 days of FO or sham. Data were analyzed with 2-way ANOVAs. RESULTS: FO increased plantaris mass independent of treatment; however, glutamine tended to enhance muscle hypertrophy compared to placebo (Placebo: 15 ± 0.6 vs. 28 ± 2 mg and Glutamine: 16 ± 0.5 vs. 34 ± 3 mg, for sham and FO, respectively, p<0.05). Maximal isometric force relative to body mass was unchanged with FO, independent of glutamine. Fatigue resistance was increased with FO compared to sham, independent of glutamine (Placebo: 39 ± 4 vs. 50 ± 5% and Glutamine: 33 ± 2 vs. 56 ± 2%, for sham and FO, respectively, p<0.05). Muscle levels of IGF-1 were significantly increased with FO, independent of glutamine (Placebo: 55 ± 7 vs. 848 ± 131 pg/mg protein and Glutamine: 25 ± 10 vs. 813 ± 174 pg/mg protein, for sham and FO, respectively, p<0.05). CONCLUSIONS: Functional overload was associated with significant hypertrophy, elevated IGF-1 levels, and increased fatigue resistance, but these adaptations were not enhanced with glutamine supplementation. Supported by Iowa Space Grant Consortium Undergraduate Research Award

Effect of glutamine ingestion on the progression of induced periodontitis: experimental study in rats

Abstract Introduction With glutamine supplementation there is better performance in the body’s defense system. Objective The aim of this study was to analyze the effect of glutamine supplementation on ligand-induced periodontal disease in rats. Material and method 48 selected male Wistar rats were divided into 4 groups (N = 12): control group (CG) including healthy animals receiving daily saline solution via gavage; glutamine group (GG) including healthy animals receiving oral glutamine supplementation by gavage at a dose of 1.5 g / kg / day; periodontitis group (PG) including animals with induced periodontal disease on both upper sides receiving daily saline solution via gavage; experimental group (EG) including animals with induced periodontal disease on both upper sides receiving daily glutamine via gavage at a dose of 1.5 g / kg / day. On the 30th day, all animals were euthanized by excess anesthetic. Result In the various analyses, the EG (116.63 ± 22.50 mm2) compared to the CG (82.32 ± 7.48 mm2) obtained a p&lt;0.05. The PG (143.15 ± 35.24 mm2) compared to the EG group (116.63 ± 22.50 mm2 ) presented a p&lt;0.05. The PG (143.15 ± 35.24 mm2) compared to the CG (82.32 ± 7.48 mm2) presented a p&lt;0.05. The GG (118.09 ± 10.4 mm2) compared to the CG (82.32 ± 7.48 mm2) presented a p&gt;0.05. Conclusion Glutamine supplementation associated with induced periodontal disease demonstrated a smaller amount of bone loss compared to the periodontitis group.

SUN-P011: Effects of Glutamine Supplementation on Critically Ill Adults: an Umbrella Review of Systematic Reviews and Meta-Analyses

SUN-P011: Effects of Glutamine Supplementation on Critically Ill Adults: an Umbrella Review of Systematic Reviews and Meta-Analyses

Effects of glutamine supplementation on body composition, food intake and energy metabolism in high fat fed mice.

enhance recovery after surgery or trauma. It has also been reported to have beneficial effects on glycaemic control in diabetic patients, while rodent studies suggest that it may reduce body weight and lessen hyperglycaemia. Objective: The present study aimed to investigate the effects of daily supplementation of glutamine to high fat diet and to assess this in a mouse model with abnormal feeding behaviour: the Snord116 knockout mouse. Research methods: Adult male C57BL/6 mice and mice with deletion of the Snord116 gene cluster (implicated in Prader-Willi syndrome) were given ad libitum access to HFD for 12 weeks. Mice of both genotypes were randomly assigned to either the treatment or non-treatment group. Animals were supplemented with glutamine in food (40 mg/g HFD). Body weight was monitored weekly. Spontaneous and fasting-induced food intake, glucose tolerance and insulin sensitivity, energy expenditure and body composition were assessed between 14 and 18 weeks of age. Results: Glutamine treatment did not attenuate the development of HFD-induced obesity in either WT or Snord116 knockout mice, with treatment and non-treatment groups within genotypes gaining weight at a similar rate during the monitoring period. There was also no difference between treatment groups within genotypes in food intake, glucose tolerance, insulin tolerance, energy expenditure or adiposity. Conclusion: Our results did not find evidence that would support beneficial metabolic effects of glutamine when administered daily; either in WT or Snord116 knockout mice fed a HFD.

Effect of Glutamine Supplementation in Patients with Inflammatory Bowel Diseases

Effect of Glutamine Supplementation in Patients with Inflammatory Bowel Diseases

Effect of Glutamine Supplementation on Chemoradiotherapy-induced Mucositis in Patients with Head and Neck Cancer

Effect of Glutamine Supplementation on Chemoradiotherapy-induced Mucositis in Patients with Head and Neck Cancer

Glutamine supplementation in cystic fibrosis: A randomized placebo-controlled trial.

Pulmonary infection and malnutrition in cystic fibrosis are associated with decreased survival. Glutamine has a possible anti-microbial effect, with a specific impact against Pseudomonas aeruginosa. We aimed to test the hypothesis that oral glutamine supplementation (21 g/day) for 8 weeks in adults with cystic fibrosis would decrease pulmonary inflammation and improve clinical status. The study design was a randomized double-blind placebo-controlled study design with an iso-nitrogenous placebo. The primary analysis was intention to treat, and the primary outcome was change in induced sputum neutrophils. Thirty-nine individuals were recruited and thirty-six completed the study. Glutamine supplementation had no impact on any of the outcome measures in the intention-to-treat analysis. In the per protocol analysis, glutamine supplementation was associated with an increase in induced sputum neutrophils (P = 0.046), total cells (P = 0.03), and in Pseudomonas isolation agar colony forming units (P = 0.04) compared to placebo. There was no effect of glutamine supplementation on markers of pulmonary inflammation in the intention-to-treat analysis.

The Effects of Glutamine Supplementation on Markers of Autophagy and Apoptosis in Peripheral Blood Mononuclear Cells from Patients with Sickle Cell Disease

Introduction: Sickle cell disease (SCD) is a hemoglobinopathy associated with an increased risk of pulmonary hypertension (PH) due to a number of mechanisms that includes iron overload, hemolysis, erythrocyte-derived arginase (which limits both nitric oxide and arginine bioavailability), functional splenectomy, and a hypercoagulable state among others. Glutathione (GSH, and its oxidized pair glutathione disulfide GSSG) is the principal thiol redox buffer in erythrocytes, which has been linked to hemolysis when depleted. Glutamine is not only a precursor to GSH, but also plays an anti-oxidant role through preservation of the intracellular nicotinamide adenine dinucleotide (NAD) levels, required for reducing GSSG back to GSH, thus decreasing the risk for hemolysis. Low erythrocyte glutamine levels are associated with risk of PH as defined by a tricuspid regurgitant jet velocity of (TRV) ≥2.5 m/s measured by Doppler echocardiography. SCD also exhibits an elevated level of circulating leukocytes, known as leukocytosis, which may contribute to vascular occlusion. The mechanism by which leukocytosis occurs is currently unknown. However, leukocyte cell death can be informative on the regulation of leukocyte cell numbers and measurement of mitochondrial BAX and caspase 9, are classic indicators of an active intrinsic cell death pathway. Autophagy is responsible for the turnover of macromolecules and organelles via the lysosomal degradative pathway. In this pathway, LC3 is important for the maturation and transport of autophagosomes and therefore, a reflection of autophagic activity. Autophagy ensures cell survival under certain conditions of nutrient deprivation or growth factor withdrawal and has also been implicated in innate and adaptive immune responses. In this study, the mitochondrial apoptotic marker BAX and the autophagy marker LC3 were examined in a SCD trial of glutamine therapy in patients at risk for PH.Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from blood samples taken from SCD (n=13) and control patients (n=7) and BAX and LC3 were measured via western blot analysis. Western blot results were evaluated via densitometry. SCD patients with PH-risk were treated with oral L-glutamine supplementation (10 mg TID) with the objective of estimating the level of cell death and autophagy proteins in circulating PBMCs from SCD patients at baseline and after glutamine supplementation. SCD patients were sampled at baseline (BL),and then at two weeks (W2), four weeks (W4), six weeks (W6), and eight weeks (W8) during the glutamine therapy.Results: Mean age for patients with SCD was 46±14; 39% were male with 54% having Hb-SS, while 46% had Hb-SC. Mean TRV was 3.0±0.6 m/s. The mean age for controls was 32± 12 and 57% were male; all controls were Hb-AA with a mean TRV of 1.8±0.6. At baseline there was no statistical difference in BAX expression between control and SCD patients. In comparison to baseline, however, supplementation with glutamine in SCD patients resulted in significantly increased expression of BAX in PMBCs by 15% over the 8 weeks of therapy; potentially indicating a restorative effect of glutamine on the intrinsic mitochondrial apoptotic pathway, which may ultimately reduce leukocytosis. In contrast, glutamine supplementation over 8 weeks, significantly reduced LC3 expression by 42% in PBMCs, suggesting a decrease in cellular autophagy, thus reducing the ability for PBMCs to remain in circulation.Conclusions: At baseline there was no difference in BAX expression between control and SCD patients, however, after 8 weeks of glutamine supplementation, PBMCs had an increased BAX expression and a decreased LC3 expression. This suggests that PBMCs from glutamine supplemented SCD patients may lose their ability to remain in circulation via apoptosis upregulation and autophagy downregulation DisclosuresWalter:Novartis: Research Funding.

Effect of glutamine supplementation and replacement of tris-egg yolk based extender with defatted cow milk on spermatozoa quality after equilibration and thawing.

Aim:The present study was designed to evaluate the effect of supplementation of glutamine and replacement of Tris-egg yolk (TE) based buffer with defatted cow milk on the spermatozoa quality after equilibration and thawing.Materials and Methods:Semen was collected from five Bhadawari bulls biweekly, and a total of 30 ejaculates were taken. The semen ejaculates were pooled and divided into three equal parts. The pooled semen was diluted by TE based extender (control), TE + glutamine (8 mM) (T1) and 50% TE + 50% deffated cow milk + glutamine (8 mM) (T2). At two stages viz. after equilibration and after 12 h of cryopreservation (thawed samples), progressive motility, percent live, and percent acrosomal damage of the spermatozoa was assessed.Results:Supplementation of glutamine improved (p<0.05) the spermatozoa quality with respect to the progressive motility, percent live and acrosomal damage both post-equilibration and post-thaw. T2 improved (p<0.05) the spermatozoa quality as compared to control, however; it was less (p<0.05) effective as compared T1 both post-equilibration and post-thaw.Conclusion:From the results of present study it can be concluded that glutamine supplementation was effective in maintaining post-equilibration and post-thaw spermatozoa quality whereas defatted cow milk was not as effective as TE based buffer in the extender in improving the spermatozoa quality.

Adaptations of Arginine's Intestinal-Renal Axis in Cachectic Tumor-Bearing Rats

Malignancies induce disposal of arginine, an important substrate for the immune system. To sustain immune function, the tumor-bearing host accelerates arginine's intestinal-renal axis by glutamine mobilization from skeletal muscle and this may promote cachexia. Glutamine supplementation stimulates argi-nine production in healthy subjects. Arginine's intestinal-renal axis and the effect of glutamine supplementation in cancer cach-exia have not been investigated. This study evaluated the long-term adaptations of the interorgan pathway for arginine production following the onset of cachexia and the metabolic effect of glutamine supplementation in the cachectic state. Fischer-344 rats were randomly divided into a tumor-bearing group (n = 12), control group (n = 7) and tumor-bearing group receiving a glutamine-enriched diet (n = 9). Amino acid fluxes and net fractional extractions across intestine, kidneys, and liver were studied. Compared to controls, the portal-drained viscera of tumor-bearing rats took up significantly more glutamine and released significantly less citrulline. Renal metabolism was unchanged in the cachectic tumor-bearing rats compared with controls. Glutamine supplementation had no effects on intestinal and renal adaptations. In conclusion, in the cachectic state, an increase in intestinal glutamine uptake is not accompanied by an increase in renal arginine production. The adaptations found in the cachectic, tumor-bearing rat do not depend on glutamine availability.

頭頸部癌化学放射線療法による口内炎に対するグルタミン含有成分栄養剤の使用経験

頭頸部癌化学放射線療法による口内炎に対するグルタミン含有成分栄養剤の使用経験

The Effect of Glutamine Supplementation on Exercise-Induced Oxidative Stress

The Effect of Glutamine Supplementation on Exercise-Induced Oxidative Stress

The effect of 2 mMol glutamine supplementation on HSP70 and TNF-α release by LPS stimulated blood from healthy children

Glutamine has been shown to promote heat shock protein 70 (HSP70) release both within experimental in vitro models of sepsis (2-10 mM) and in adults post trauma (0.5 g/kg), although the efficacy varies and is dependent on the model used. The effect of glutamine supplementation on HSP70 release in children is less clear. Therefore, the aim of this study was to investigate the effect of 2 mM glutamine added to incubation media on HSP70 and inflammatory mediator release in an in vitro model of paediatric sepsis using whole blood from healthy paediatric volunteers. An in vitro whole blood endotoxin stimulation model using 1 μg/ml lipopolysaccharide (LPS) over a 24 h time period was used to investigate the effects of 2 mM glutamine on HSP70 and inflammatory mediator release in healthy children. The addition of 2 mM glutamine to the incubation media significantly increased HSP70 release over time (p < 0.05). This was associated with an early pro-inflammatory effect on TNF-α release at 4 h (p < 0.005) which was not seen at 24 h. There was a non significant trend towards higher levels of IL-6 and IL-10 following the addition of 2 mM glutamine, which appears to differ from the response reported in adult and animal models. Glutamine supplementation of incubation media promotes HSP70 and early TNF- α release in an in vitro model using blood samples from healthy children.

Effects of glutamine supplementation on brain development of very preterm children: A followup study at school-age

Effects of glutamine supplementation on brain development of very preterm children: A followup study at school-age

Effect of glutamine supplementation on cardiovascular risk factors in patients with type 2 diabetes

ObjectiveThe aim of this study was to assess clinical relevance of long-term oral glutamine supplementation on lipid profile and inflammatory and metabolic factors in patients with diabetes. MethodSixty-six patients with type 2 diabetes between the ages of 18 and 65 y were randomized to receive glutamine 30 g/d (10 g powder, three times a day) or placebo, in a double-blind, placebo-controlled trial during a 6-wk treatment period. Fifty-three patients completed the trial. Independent samples t test and analysis of covariance were used. ResultsAfter a 6-wk treatment period, a significant difference was observed between the two groups in body fat mass (P = 0.01) and percentage of body fat (P = 0.008). Moreover, a significant reduction in waist circumference (P < 0.001) and a tendency for an increase in fat-free mass (P = 0.03), with no change in body weight and body mass index (BMI) was found. Enhancement in body fat-free mass was mainly attributed to trunk (P = 0.03). There was a downward trend in systolic blood pressure (P = 0.005) but not diastolic. Fasting blood glucose (mmol/L) concentration significantly decreased after the 6-wk intervention (P = 0.04). Mean hemoglobin A1c was significantly different between the groups at week 6 (P = 0.04). No significant difference was detected for fasting insulin, homeostasis model assessment for insulin resistance and quantitative insulin sensitivity index between groups (P > 0.05). No significant difference was observed between groups in total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglyceride. No treatment effect on C-reactive protein was found (P = 0.44). ConclusionWe demonstrated that the 6-wk supplementation with 30 g/d glutamine markedly improved some cardiovascular risk factors, as well as body composition, in patients with type 2 diabetes. Future glutamine dose–response studies are warranted in these areas.

The influence of parenteral glutamine supplementation on glucose homeostasis in critically ill polytrauma patients—A randomized-controlled clinical study

Rapid onset of resistance to insulin is a prominent component of stress metabolism in multiple trauma patients. Recent studies have clarified the role of amino acids (especially glutamine) in glucose transportation and the benefits of parenteral alanyl-glutamine supplementation (0.3-0.6 g/kg/day) in glucose homeostasis. The aims of this study are to evaluate the incidence of hyperglycemic episodes and the need for exogenous insulin to maintain stable glucose levels in critically ill polytrauma patients supplemented with parenteral glutamine dipeptide (Dipeptiven(®)) versus standard nutritional support. This was an open-label randomized-controlled trial of 82 polytrauma patients aged 20-60 years old, randomly assigned into two equal groups independent of sex, age and Injury Severity Score. We excluded patients with diabetes mellitus, or renal or hepatic failure. One group received parenteral Dipeptiven(®) supplementation of 0.5 g/kg/day and the other received standard isocaloric isoproteinic nutritional support. We found that 63% of patients in the glutamine-supplemented group had no hyperglycemic episodes; only 37% required exogenous insulin (mean daily requirement of 44 units/day). In the control group, 51% of patients required insulin (mean daily requirement 63 unit/day; p = 0.0407). The effect of glutamine supplementation on glucose homeostasis is associated with a lower incidence of hyperglycemia among critically ill polytrauma patients, and leads to a lower mean daily dose of insulin. Controlled-trials.com Identifier: ISRCTN71592366 (http://www.controlled-trials.com/ISRCTN71592366/ISRCTN71592366).

Dietary l-glutamine supplementation increases Pasteurella multocida burden and the expression of its major virulence factors in mice

This study was conducted to determine the effects of graded doses of L-glutamine supplementation on the replication and distribution of Pasteurella multocida, and the expression of its major virulence factors in mouse model. Mice were randomly assigned to the basal diet supplemented with 0, 0.5, 1.0 or 2.0% glutamine. Pasteurella multocida burden was detected in the heart, liver, spleen, lung and kidney after 12h of P. multocida infection. The expression of major virulence factors, toll-like receptors (TLRs), proinflammatory cytokines (interleukin-1 beta, interleukin-6, and tumor necrosis factor alpha) and anti-oxidative factors (GPX1 and CuZnSOD) was analyzed in the lung and spleen. Dietary 0.5% glutamine supplementation has little significant effect on these parameters, compared to those with basal diet. However, results showed that a high dose of glutamine supplementation increased the P. multocida burden (P<0.001) and the expression of its major virulence factors (P<0.05) as compared to those with a lower dose of supplementation. In the lung, high dose of glutamine supplementation inhibited the proinflammatory responses (P<0.05) and TLRs signaling (P<0.05). In the spleen, the effect of glutamine supplementation on different components in TLR signaling depends on glutamine concentration, and high dose of glutamine supplementation activated the proinflammatory response. In conclusion, glutamine supplementation increased P. multocida burden and the expression of its major virulence factors, while affecting the functions of the lung and spleen.

Effect of intermittent glutamine supplementation on skeletal muscle is not long-lasting in very old rats.

Muscle is the major site for glutamine synthesis via glutamine synthetase (GS). This enzyme is increased 1.5-2 fold in 25-27-mo rats and may be a consequence of aging-induced stress. This stimulation is similar to the induction observed following a catabolic state such as glucocorticoid treatment (6 to 24 months). Although oral glutamine supply regulates the plasma glutamine level, nothing is known if this supplementation is interrupted before the experiment. Adult (8-mo) and very old (27-mo) female rats were exposed to intermittent glutamine supplementation for 50 % of their age lifetime. Treated rats received glutamine added to their drinking water and control rats water alone but the effect of glutamine supplementation was only studied 15 days after the last supplementation. Glutamine pretreatment discontinued 15 days before the experiment increased plasma glutamine to ~ 0.6 mM, a normal value in very old rats. However, it failed to decrease the up-regulated GS activity in skeletal muscle from very old rats. Our results suggest that long-term treatment with glutamine started before advanced age but discontinued 15 days before rat sacrifice is effective in increasing plasma glutamine to recover basal adult value and in maintaining plasma glutamine in very old rats, but has no long-lasting effect on the GS activity of skeletal muscle with advanced age.

Effect of glutamine supplementation and resistive training in signaling pathways of protein synthesis and degradation in rat skeletal muscle

The effect of physical training and glutamine supplementation on signaling pathways involved in protein synthesis (Akt, 4EBP‐1 and S6) and degradation (FOXO, MuRF‐1 and MAFbx) of rat skeletal muscle was determined by real time PCR and western blotting in the following groups: 1) control (C); 2) trained (T); 3) control supplemented with glutamine (G); and 4) trained supplemented with glutamine (GT). Exercise protocol was conducted once every 3 days, during 5 weeks. Each training session consisted of six climbs in a vertical ladder (1.1 m; 80° from horizontal). EDL muscle mass was not changed, but a significant increase in the cross‐sectional area of the fibers was observed. Expression of FOXO‐1, Akt, atrogin‐1, Murf‐1, 4E‐BP1, and S6 was not altered. In contrast, phosphorylated S6 and 4EBP‐1 expression was significantly increased in the G and GT groups, and 26S proteasome activity decreased in the T group as compared to C group. Our results suggest that glutamine supplementation led to an increase of the phosphorylation of state 4EBP‐1 and S6. The 5 weeks of a physical training protocol described in this study in rats is a useful model to investigated the molecular mechanisms underlying the increased muscle mass due to long‐duration exercise. This research was supported by FAPESP, CNPq, CAPES and Guggenheim Foundation.

Reverse Effects of DPI Administration Combined With Glutamine Supplementation on Function of Rat Neutrophils Induced by Overtraining

To examine the excessive reactive oxygen species (ROS) mediated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and the combined effect of glutamine supplementation and diphenyleneiodonium (DPI) on the function of neutrophils induced by overtraining. Fifty male Wistar rats were randomly divided into 5 groups: control group (C), overtraining group (E), DPI-administration group (D), glutamine-supplementation group (G), and combined DPI and glutamine group (DG). Blood was sampled from the orbital vein after rats were trained on treadmill for 11 wk. Cytokine and lipid peroxidation in blood plasma were measured by enzyme-linked immunosorbent assay. The colocalization between gp91phox and p47phox of the NADPH oxidase was detected using immunocytochemistry and confocal microscopy. The activity of NADPH oxidase was assessed by chemiluminescence. Neutrophils' respiratory burst and phagocytosis function were measured by flow cytometry. NADPH oxidase was activated by overtraining. Cytokine and lipid peroxidation in blood plasma and the activity of NADPH oxidase were markedly increased in Group E compared with group C. Neutrophil function was lower in group E than group C. Both lower neutrophils function and higher ROS production were reversed in Group DG. The glutamine and DPI interference alone in group D and group G was less effective than DPI and glutamine combined in group DG. Activation of NADPH oxidase is responsible for the production of superoxide anions, which leads to excessive ROS and is related to the decrease in neutrophil function induced by overtraining. The combined DPI administration and glutamine supplementation reversed the decreased neutrophil function after overtraining.