Enhanced Glutamine Availability Exerts Different Effects on Protein and Amino Acid Metabolism in Skeletal Muscle From Healthy and Septic Rats

Background: Enhanced glutamine (GLN) intake may affect the catabolism of branched‐chain amino acids (BCAAs; valine, leucine, and isoleucine), which play a regulatory role in protein turnover. We examined the effects of enhanced GLN availability on leucine oxidation, amino acid concentrations, and protein metabolism in muscles from healthy and septic rats. Methods: Cecal ligation and puncture were used as a model of sepsis. Twenty‐four hours after surgery, the soleus (SOL, red muscle) and the extensor digitorum longus (EDL, white muscle) were incubated in medium containing 0.5 or 2.0 mM GLN. Protein breakdown, protein synthesis, and leucine oxidation were determined via 3‐methylhistidine release, muscle L‐[1‐¹⁴C]leucine radioactivity, and the radioactivity of released ¹⁴CO₂, respectively. Results: In muscles from septic animals, increased proteolysis and leucine oxidation and decreased protein synthesis were detected. These effects were more pronounced in the EDL. In septic muscles, the addition of GLN decreased leucine oxidation in both muscles and increased protein synthesis in the EDL. In muscles from untreated animals, decreased leucine oxidation after the addition of GLN to the medium was associated with decreased protein synthesis in the SOL and decreased concentrations of serine, glycine, histidine, alanine, arginine, proline, and lysine in both muscles. Conclusions: White muscle fibers are more sensitive to septic stimuli than red fibers are. In sepsis, enhanced GLN intake may ameliorate GLN deficiency, inhibit BCAA catabolism, and stimulate protein synthesis. In the healthy state, surplus of GLN may lead to severe alterations in the intramuscular concentration of several amino acids and impair protein synthesis.     

Branched-chain amino acids and ammonia metabolism in liver disease: Therapeutic implications

The rationale for recommendation of branched-chain amino acids (BCAA; valine, leucine, and isoleucine) in treatment of liver failure is based on their unique pharmacologic properties, stimulatory effect on ammonia detoxification to glutamine (GLN), and decreased concentrations in liver cirrhosis. Multiple lines of evidence have shown that the main cause of the BCAA deficiency in liver cirrhosis is their consumption in skeletal muscle for synthesis of glutamate, which acts as a substrate for ammonia detoxification to GLN and that the BCAA administration to patients with liver failure may exert a number of positive effects that may be more pronounced in patients with marked depression of BCAA levels. On the other hand, due to the stimulatory effect of BCAA on GLN synthesis, BCAA supplementation may lead to enhanced ammonia production from GLN breakdown in the intestine and the kidneys and thus exert harmful effects on the development of hepatic encephalopathy. Therefore, to enhance therapeutic effectiveness of the BCAA in patients with liver injury, their detrimental effect on ammonia production, which is negligible in healthy people and/or patients with other disorders, should be avoided. In treatment of hepatic encephalopathy, simultaneous administration of the BCAA (to correct amino acid imbalance and promote ammonia detoxification to GLN) with α-ketoglutarate (to inhibit GLN breakdown to ammonia in enterocytes) and/or phenylbutyrate (to enhance GLN excretion by the kidneys) is suggested. Attention should be given to the type of liver injury, gastrointestinal bleeding, signs of inflammation, and the dose of BCAA.     

Glutamine therapy improves outcome of in vitro and in vivo experimental colitis models

Background: Pharmacologic doses of glutamine (GLN) can improve clinical outcome following acute illness and injury. Recent studies indicate enhanced heat shock protein (HSP) expression is a key mechanism underlying GLN's protection. However, such a link has not yet been tested in chronic inflammatory states, such as experimental inflammatory bowel disease (IBD). Methods: Experimental colitis was induced in Sprague‐Dawley rats via oral 5% dextran sulfate sodium (DSS) for 7 days. GLN (0.75 g/kg/d) or sham was administered to rats by oral gavage during 7‐day DSS treatment. In vitro inflammatory injury was studied using YAMC colonic epithelial cells treated with varying concentrations of GLN and cytokines (tumor necrosis factor–α/interferon‐γ). Results: Pharmacologic dose, bolus GLN attenuated DSS‐induced colitis in vivo with decreased area under curve for bleeding (8.06 ± 0.87 vs 10.38 ± 0.79, P < .05) and diarrhea (6.97 ± 0.46 vs 8.53 ± 0.39, P < .05). This was associated with enhanced HSP25 and HSP70 in colonic mucosa. In vitro, GLN enhanced cell survival and reduced proapoptotic caspase3 and poly(ADP‐ribose) polymerase cleavage postcytokine injury. Cytokine‐induced inducible nitric oxide synthase expression and nuclear translocation of nuclear factor‐κB p65 subunit were markedly attenuated at GLN concentrations above 0.5 mmol/L. GLN increased cellular HSP25 and HSP70 in a dose‐dependent manner. Conclusions: These data demonstrate the therapeutic potential of GLN as a “pharmacologically acting nutrient” in the setting of experimental IBD. GLN sufficiency is crucial for the colonic epithelium to mount a cell‐protective, antiapoptotic, and anti‐inflammatory response against inflammatory injury. The enhanced HSP expression observed following GLN treatment may be responsible for this protective effect.     

Glutamine reduces the expression of leukocyte integrins leukocyte function–associated antigen-1 and macrophage antigen-1 in mice exposed to arsenic

Chronic arsenic exposure results in an increased oxidative stress and inflammation in the body. Glutamine (GLN) is an amino acid considered to have immunomodulatory effects and attenuate the inflammatory reaction. This study was designed to examine the effect of GLN supplementation on inflammatory-related leukocyte integrin expression and in vitro splenocyte cytokine production in mice exposed to arsenic. Mice were assigned to the control and experimental groups. The control group drank deionized water, whereas the experimental group drank deionized water containing 50 ppm of sodium arsenite. Each control and experimental group was further divided into 2 subgroups and fed diets for 5 weeks. One subgroup was fed a semipurified diet, whereas the other subgroup was fed a diet where part of the casein was replaced with GLN, which provided 25% of the total amino acid nitrogen. The results showed that plasma GLN levels of mice in the arsenic group were significantly lower than those in the control groups. Glutamine supplementation reversed the depletion of plasma GLN in the arsenic group. β₂ intergins, including leukocyte function–associated antigen-1 and macrophage antigen-1 expressed by leukocytes, were significantly higher in the arsenic group than the control groups. Glutamine supplementation reduced leukocyte integrin expression in mice exposed to arsenic. There were no differences in interleukin 4, interleukin 6, interferon γ, and tumor necrosis factor α production between the 2 arsenic groups when splenocytes were stimulated with mitogen. These results suggest that arsenic exposure results in depletion of plasma GLN and higher leukocyte integrin expression. Glutamine supplementation normalized the plasma GLN levels and reduced leukocyte leukocyte function–associated antigen-1 and macrophage antigen-1 expression. However, cytokine modulation may not be responsible for reducing leukocyte integrin expression in mice exposed to arsenic.     

Glutamine Improves Innate Immunity and Prevents Bacterial Enteroinvasion During Parenteral Nutrition

Background: Patients receiving parenteral nutrition (PN) are at increased risk of infectious complications compared with enteral feeding, which is in part explained by impaired mucosal immune function during PN. Adding glutamine (GLN) to PN has improved outcome in some clinical patient groups. Although GLN improves acquired mucosal immunity, its effect on innate mucosal immunity (defensins, mucus, lysozymes) has not been investigated. Methods: Forty‐eight hours following venous cannulation, male Institute of Cancer Research mice were randomized to chow (n = 10), PN (n = 12), or PN + GLN (n = 13) for 5 days. Small intestine tissue and luminal fluid were collected for mucin 2 (MUC2), lysozyme, cryptdin 4 analysis, and luminal interleukin (IL)–4, IL‐10, and IL‐13 level measurement. Tissue was also harvested for ex vivo intestinal segment culture to assess tissue susceptibility to enteroinvasive Escherichia coli. Results: In both luminal and tissue samples, PN reduced MUC2 and lysozyme (P < .0001, respectively) compared with chow, whereas GLN addition increased MUC2 and lysozyme (luminal, P < .05; tissue, P < .0001, respectively) compared with PN alone. PN significantly suppressed cryptdin 4 expression, while GLN supplementation significantly enhanced expression. IL‐4, IL‐10, and IL‐13 decreased significantly with PN compared with chow, whereas GLN significantly increased these cytokines compared with PN. Functionally, bacterial invasion increased with PN compared with chow (P < .05), while GLN significantly decreased enteroinvasion to chow levels (P < .05). Conclusions: GLN‐supplemented PN improves innate immunity and resistance to bacterial mucosal invasion lost with PN alone. This work confirms a clinical rationale for providing glutamine for the protection of the intestinal mucosa.     

Effects of oral supplementation with glutamine and alanyl-glutamine on glutamine,glutamate, and glutathione status in trained rats and subjected to long-duration exercise

ObjectiveWe investigated the effect of supplementation with the dipeptide L-alanyl-L-glutamine (DIP) and a solution containing L-glutamine and L-alanine, both in the free form, on the plasma and tissue concentrations of glutamine, glutamate, and glutathione (GSH) in rats subjected to long-duration exercise.MethodsRats were subjected to sessions of swim training. Twenty-one days before sacrifice, the animals were supplemented with DIP (1.5 g/kg, n = 6), a solution of free L-glutamine (1 g/kg) and free L-alanine (0.61 g/kg; GLN + ALA, n = 6), or water (CON, n = 6). Animals were sacrificed before (TR, n = 6) or after (LD, n = 6) long-duration exercise. Plasma concentrations of glutamine, glutamate, glucose, and ammonia and liver and muscle concentrations of glutamine, glutamate, and reduced and oxidized (GSSG) GSH were measured.ResultsHigher concentrations of plasma glutamine were found in the DIP-TR and GLN + ALA-TR groups. The CON-LD group showed hyperammonemia, whereas the DIP-LD and GLN + ALA-LD groups exhibited lower concentrations of ammonia. Higher concentrations of glutamine, glutamate, and GSH/GSSG in the soleus muscle and GSH and GSH/GSSG in the liver were observed in the DIP-TR and GLN + ALA-TR groups. The DIP-LD and GLN + ALA-LD groups exhibited higher concentrations of GSH and GSH/GSSG in the soleus muscle and liver compared with the CON-LD group.ConclusionChronic oral administration of DIP and free GLN + ALA before long-duration exercise represents an effective source of glutamine and glutamate, which may increase muscle and liver stores of GSH and improve the redox state of the cell.     

择期手术／意外创伤后补充谷氨酰胺的效应

The etabolic response to injury,whether a controlled electivesurgical procedure or an accidental injury,is characterized by the breakdown of skeletal muscle protein and the translocation of the amino acids to visceral organs and the wound.At these sites the substrate serves to dnhance host defenses,and support vital organ function and wound repair.Glutamine (GLN) plays a major role in this process,accounting for approximately one-third of the translocated nitrogen.From the data available,GLN supplemented intravenous nutrition in patients undergoing elective surgery improved nitrogen balance,helped correct the decreased GLN concentration found in the free intracellular skeletal muscle amino acid pool and enhanced net protein synthesis (particularly in skeletal muscel).Six rancomized blinded trials(two multicentered investigations) have reported a dereased length in hospital stay in postoperative patients receiving GLN supplementation.Following blunt trauma,GLN supplementation increased plasma concentrations,attenuated the immunosuppression commonly observed and decreased the rate of infection.Patients with burn injury have low GLN plasma and intramuscular concentrations,but turnover and synthesis rate are accelerated,yet apparently inadequate to support normal concentrations.These data suggests that GLN supplementation has important effects in catabolic surgical patients,but the exact mechanisms to explain these events remain unknown and more research is required to explain the apparent benefits of dietary GLN.     

Cisplatin Upregulates Glutamine Transport in Human Intestinal Epithelial Cells

Background: Glutamine (GLN) prevents the intestinal mucosal injury induced by chemotherapy, although the mechanism of this protective action has not yet been elucidated. Amino acid transport across the plasma membrane is essential for supplying enterocytes with amino acids for cellular metabolism. It was hypothesized that chemotherapy stimulates GLN transport, which enables GLN to be used more efficiently as a metabolic fuel. Methods: A rat model was used to examine the effect of enteral GLN on intestinal mucosal injury induced by intraperitoneal injection of cisplatin (7.0 mg/kg of body weight). The effects of cisplatin on amino acid transport and the expression of messenger RNA and protein were evaluated by real‐time polymerase chain reaction and Western blot analysis, respectively, in the human intestinal epithelial cell line Caco‐2. The effects of cisplatin on glutaminase activity and intracellular glutathione were also studied. Results: GLN prevented mucosal atrophy induced by cisplatin in rats. In Caco‐2 cells, cisplatin significantly increased GLN transport and the expression of GLN transporter ASCT2 messenger RNA and protein. Leucine, but not glutamate, transport significantly increased in the cisplatin‐treated group due to the increase in LAT1 (leucine transporter) protein expression. Glutaminase activity and intracellular glutathione increased significantly in the cisplatin‐treated group. Conclusions: Bolus enteral GLN prevents intestinal mucosal injury induced by cisplatin in rats, as demonstrated by increased GLN transport and increased GLN transporter expression after cisplatin administration.     

Glutamine attenuates lipopolysaccharide-induced acute lung injury

ObjectivesIt has been reported that glutamine (GLN) can attenuate acute lung injury after sepsis. GLN is also thought to be a precursor of glutathione (GSH) synthesis. Using the GSH synthesis blocker, L-buthionine-(S,R)-sulfoximine (BSO), we investigated the role of GSH synthesis in the protective effect of GLN on acute lung injury.MethodsIn this study, we used an acute lung injury model induced by intratracheal injection of lipopolysaccharide (1 mg · mL^?1 · kg^?1). GLN (0.75 g/kg, intravenous) and BSO (2 mmol/kg, intraperitoneal) were administrated simultaneously. At 2 and 18 h after the injections, the rats were sacrificed by right ventricular puncture and bronchoalveolar lavage was done. The lower right lung was excised for histologic examination. Total protein concentration and total cell and neutrophil counts in the bronchoalveolar lavage fluid were determined. CD11b expression in the blood was determined by flow cytometry. We also analyzed myeloperoxidase activity, and GSH and interleukin-8 levels in lung tissues.ResultsGLN supplementation reduced the total protein concentration and total cell and neutrophils counts in bronchoalveolar lavage fluid after lipopolysaccharide challenge. GLN enhanced GSH synthesis and attenuated interleukin-8 release and myeloperoxidase activity in lung tissues. GLN also decreased CD11b expression in blood neutrophils and prevented lung histologic changes. BSO abolished the effects of GLN and attenuated its protection on acute lung injury.ConclusionThese results indicate that GLN could prevent neutrophil recruitment and infiltration, protect the alveolar barrier, and attenuate inflammatory injury during sepsis. This effect may be related to enhanced GSH synthesis.     

Evaluation of the effects of a preoperative 2-hour fast with maltodextrine and glutamine on insulin resistance, acute-phase response, nitrogen balance, and serum glutathione after laparoscopic cholecystectomy: a controlled randomized trial

Background: Prolonged preoperative fasting increases insulin resistance (IR). The authors investigated whether an abbreviated preoperative fast with glutamine (GLN) plus a carbohydrate (CHO)–based beverage would improve the organic response after surgery. Methods: Forty‐eight female patients (19‐62 years) were randomized to either standard fasting (control group) or to fasting with 1 of 3 different beverages before video‐cholecystectomy. Beverages were consumed 8 hours (400 mL; placebo group: water; GLN group: water with 50 g maltodextrine plus 40 g GLN; and CHO group: water with 50 g maltodextrine) and 2 hours (200 mL; placebo: water; GLN: water with 25 g maltodextrine plus 10 g GLN; and CHO: water with 25 g maltodextrine) before anesthesia. Blood samples were collected pre‐ and postoperatively. Results: The mean (SEM) postoperative homeostasis model assessment–insulin resistance was greater (P < .05) in control patients (4.3 [1.3]) than in the other groups (placebo, 1.6 [0.3]; CHO, 2.3 [0.4]; and GLN, 1.5 [0.1]). Glutathione was significantly higher (P < .01) in the GLN group than in both CHO and control groups. Interleukin‐6 increased in all groups except the GLN group. The C‐reactive protein/albumin ratio was higher (P < .05) in controls than in CHO and GLN groups. The nitrogen balance was less negative in GLN (–2.5 [0.8] gN) than in both placebo (–9.0 [2] gN; P = .001) and control (–6.6 [0.4] gN; P = .04) groups. Conclusions: Preoperative intake of a GLN‐enriched CHO beverage appears to improve IR and antioxidant defenses and decreases the inflammatory response after video‐cholecystectomy.     

Distinct Effects of Growth Hormone and Glutamine on Activation of Intestinal Stem Cells

Background: For patients with short bowel syndrome under parenteral nutrition support, growth hormone (GH) and glutamine (GLN) have been found to help the growth of intestinal mucosa. In this research, we studied the effects of GH and GLN on intestinal stem cells (ISCs). Methods: The in vitro and in vivo effects of GH and/or GLN on ISCs were evaluated by observing the ability of ISCs to form organoids in a Matrigel culture system. The expression levels of stemness and differentiation markers in ISCs and organoids were assessed using quantitative real‐time polymerase chain reaction, immunofluorescence assay, and immunohistochemistry staining. Results: In vitro administration of GH activated the stemness of ISCs, whereas GLN enhanced the expression of chromogranin A and Muc2, which are differentiation markers in enteroendocrine and goblet cells, respectively. Administration of GH or GLN in mice showed that GH, but not GLN, upregulated the proliferative activity of ISCs with increased formation of crypt organoids. In addition, GH increased the expression of Lgr5 and GLN enhanced expression of Muc2 in the crypt fractions of the intestines in mice. Conclusion: These results suggest that GH mainly enhances proliferative activities, whereas GLN promotes the differentiation potential of ISCs.     

Glutamine restores myocardial cytochrome C oxidase activity and improves cardiac function during experimental sepsis

Background: Cardiac dysfunction occurs commonly in sepsis. Impaired mitochondrial function is a potential cause of sepsis‐associated myocardial depression. Cytochrome oxidase (COX), the terminal oxidase of the electron transport chain, is inhibited in the septic heart. Glutamine (GLN) increases Krebs cycle intermediates and supports oxidative phosphorylation. Exogenous GLN has been shown to restore myocardial adenosine triphosphate levels and cardiac function following ischemia–reperfusion injury. The authors hypothesize that exogenous GLN will abrogate sepsis‐induced myocardial COX inhibition and improve sepsis‐associated myocardial depression. Methods: Under general anesthesia, male Sprague‐Dawley rats underwent cecal ligation and double puncture (CLP) or sham operation. At the time of operation, rats underwent intraperitoneal injection of either GLN (0.75 g/kg) or an equal volume of saline. Twenty‐four hours after the procedure, animals were killed, cardiac ventricles harvested, and mitochondria isolated. Steady‐state COX kinetic activity was measured and normalized to citrate synthase activity. Steady‐state levels of COX subunit I protein were determined with immunoblot analysis. Cardiac function was assessed using an isolated rat heart preparation. Five animals per group were evaluated. Significance was determined with analysis of variance and post hoc Tukey test. Results: CLP significantly decreased myocardial COX activity, oxygen consumption, left ventricular pressure (LVP), and pressure developed during isovolumic contraction (+dP/dt) and relaxation (?dP/dt). GLN restored COX activity to sham levels, significantly increased myocardial oxygen extraction and consumption, increased LVP toward sham values, and increased ±dP/dt by >30% following CLP. Conclusion: The beneficial effects of GLN therapy during sepsis may be in part due to restoration of oxidative phosphorylation and abrogation of sepsis‐associated myocardial depression.     

Effect of Glutamine Dipeptide Supplementation on Primary Outcomes for Elective Major Surgery: Systematic Review and Meta-Analysis

To evaluate if glutamine (GLN) supplementation may affect primary outcomes in patients undergoing major elective abdominal operations, we performed a systematic literature review of randomized clinical trials (RCTs) published from 1983 to 2013 and comparing intravenous glutamine dipeptide supplementation to no supplementation in elective surgical abdominal procedures. A meta-analysis for each outcome (overall and infectious morbidity and length of stay) of interest was carried out. The effect size was estimated by the risk ratio (RR) or by the weighted mean difference (WMD). Nineteen RCTs were identified with a total of 1243 patients (640 receiving GLN and 603 controls). In general, the studies were underpowered and of medium or low quality. GLN supplementation did not affect overall morbidity (RR = 0.84, 95% CI 0.51 to 1.36; p = 0.473) and infectious morbidity (RR = 0.64; 95% CI = 0.38 to 1.07; p = 0.087). Patients treated with glutamine had a significant reduction in length of hospital stay (WMD = −2.67; 95% CI = −3.83 to −1.50; p < 0.0001). In conclusion, GLN supplementation appears to reduce hospital stay without affecting the rate of complications. The positive effect of GLN on time of hospitalization is difficult to interpret due to the lack of significant effects on surgery-related morbidity.     

Glutamine Supplementation Decreases Intestinal Permeability and Preserves Gut Mucosa Integrity in an Experimental Mouse Model

Background: Glutamine (GLN) is the preferred fuel for enterocytes, and GLN supplementation is critical during stressful conditions. The aim of this study was to evaluate the effect of GLN on intestinal barrier permeability and bacterial translocation in a murine experimental model. Methods: Swiss male mice (25–30 g) were randomized into 3 groups: (1) sham group; (2) intestinal obstruction (IO) group; (3) IO and GLN (500 mg/kg/d) group. Two different experiments were carried out to assess intestinal permeability and bacterial translocation. In the first experiment, the animals were divided into the 3 groups described above and received diethylenetriamine pentaacetate radiolabeled with technetium (^99mTc) on the eighth day. At different time points after intestinal obstruction, blood was collected to determine radioactivity. The animals were killed, and the small intestine was removed for histological analyses. In the bacterial translocation study, on the eighth day all groups received Escherichia coli labeled with ^99mTc. After 90 minutes, the animals underwent intestinal obstruction and were killed 18 hours later. Blood, mesenteric lymph nodes, liver, spleen, and lungs were removed to determine radioactivity. Statistical significance was considered when P ≤ .05. Results: The levels of intestinal permeability and bacterial translocation were higher in the IO group than in the sham and GLN groups (P < .05). GLN decreased intestinal permeability and bacterial translocation to physiologic levels in the treated animals and preserved intestinal barrier integrity. Conclusions: GLN had a positive impact on the intestinal barrier by reducing permeability and bacterial translocation to physiologic levels and preserving mucosal integrity.     

Efficacy and tolerability of a prolonged release ferrous sulphate formulation in iron deficiency anaemia: a non-inferiority controlled trial

Background  

Iron deficiency anaemia (IDA) is the last stage of iron deficiency, consecutive to an imbalance between iron supply through food intake and iron loss through physiological or pathological processes. As well as by haemoglobin levels, IDA is diagnosed by measuring biomarkers of iron stores. Women are most affected by IDA since their teenage years, as menstruation constitutes a chronic iron loss. Oral supplementation with ferrous sulphate is an effective therapy, but gastrointestinal side effects may impair treatment compliance.     

Dietary treatment of rheumatoid cachexia with beta-hydroxy-beta-methylbutyrate, glutamine and arginine: a randomised controlled trial

BACKGROUND & AIMS: Rheumatoid arthritis (RA) is complicated by cytokine-driven alterations in protein and energy metabolism and consequent muscle wasting (cachexia). The aim of this randomised controlled trial was to investigate the efficacy of a mixture of beta-hydroxy-beta-methylbutyrate, glutamine and arginine (HMB/GLN/ARG) as nutritional treatment for rheumatoid cachexia. METHODS: Forty RA patients supplemented their diet with either HMB/GLN/ARG or a nitrogen (7.19 g/day) and calorie (180 kcal/day) balanced mixture of alanine, glutamic acid, glycine, and serine (placebo) for 12 weeks. Body composition and other outcomes were assessed at baseline and follow-up, and analysed by mixed ANOVA. RESULTS: Dietary supplementation with HMB/GLN/ARG was not superior to placebo in the treatment of rheumatoid cachexia (groupxtime interactions P>0.05 for all outcomes). Both amino acid mixtures significantly increased (main effect of time) fat-free mass (727+/-1186 g, P<0.01), total body protein (719+/-1703 g, P=0.02), arms (112+/-183 g, P<0.01) and legs (283+/-534 g, P<0.01) lean mass, and some measures of physical function. No significant adverse event occurred during the study, but patients in the HMB/GLN/ARG group reported fewer gastrointestinal complaints compared to placebo. CONCLUSIONS: Dietary supplementation with HMB/GLN/ARG is better tolerated but not more effective in reversing cachexia in RA patients compared to the mixture of other non-essential amino acids used as placebo. Further controlled studies are necessary to confirm the beneficial anabolic and functional effects of increased nitrogen intake in this population.     

Glutamine supplementation increases postprandial energy expenditure and fat oxidation in humans

BACKGROUND: Glutamine interacts with insulin-mediated glucose disposal, which is a component of the increase in energy expenditure (EE) after a meal. The study aim was to examine if glutamine supplementation alters postmeal nutrient oxidation. METHODS: Ten healthy young adults consumed a mixed meal (6.5 kcal/kg, 14%:22%:64% = protein:fat:carbohydrate) containing either glutamine (GLN:1.05 kcal/kg) or an isocaloric amino acid mixture (alanine: glycine:serine = 2:1:0.5; CON). GLN and CON treatments were administered on separate days in random order for each subject. EE, nonprotein respiratory quotient (RQ), and fat and carbohydrate oxidation rates were assessed using indirect calorimetry for 30 minutes before and for 360 minutes after meal ingestion. RESULTS: Premeal EE and RQ were similar between treatments. The increase in EE above basal during both early (0-180 minutes) and late (180-360 minutes) postmeal phases was greater in GLN than in CON (p < .05), resulting in postmeal EE being 49% greater during the total postmeal phase (p < .05). Net change of carbohydrate oxidation was 38% higher during the early phase with GLN (p < .05), whereas it was 71% lower during the later phase (p < .05). GLN enhanced fat oxidation by approximately 42 kcal compared with CON during the late phase (p < .05). CONCLUSIONS: Glutamine supplementation with a mixed meal alters nutrient metabolism to increase postmeal EE by increasing carbohydrate oxidation during the early postmeal phase and fat oxidation during the late postmeal phase. Consideration must be given to the potential that these postprandial changes in EE are related to glutamine-mediated changes in insulin action and consequently glucose disposal.     

Heterocyclic Aromatic Amine [HCA] Intake and Prostate Cancer Risk: Effect Modification by Genetic Variants

The association between heterocyclic aromatic amine (HCA) intake and prostate cancer (PCa) risk may be modified by genetic variation in enzymes involved in HCA metabolism. We examined this question in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition Heidelberg cohort. The study included 204 PCa cases and 360 matched controls. At baseline, participants provided dietary and lifestyle data and blood samples that were used for genotyping. Dietary HCA intake—2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP), 2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline (MeIQx), and 2-amino-3,4,8-dimethylimidazo [4,5-f]quinoxaline (DiMeIQx—was estimated using information on meat consumption, cooking methods, and browning degree. Risk estimates for gene × HCA interactions were calculated by unconditional logistic regression. We found inverse associations between PhIP, MeIQx, or DiMeIQx intake and PCa risk when having <2 deletions of the GSTT1 and GSTM1 genes (P _interaction: 0.03, 0.01, and 0.03, respectively), which is supported by analysis of darkly browned meat consumption data. Statistically significant effect modification of both HCA (DiMeIQx) and darkly browned meat intake and PCa risk was observed for allelic variants of MnSOD (rs4880) (P _interaction: 0.02). Despite limitations due to study size, we conclude that the association between HCA intake and PCa risk could be modified by polymorphisms of GSTT1, GSTM1, and MnSOD.     

Effect of Acute and Chronic Dietary Supplementation with Green Tea Catechins on Resting Metabolic Rate,Energy Expenditure and Respiratory Quotient: A Systematic Review

The consumption of green tea catechins (GTC) is associated with modulations of fat metabolism and consequent weight loss. The aim of this systematic review was to investigate the effect of GTC on resting metabolic rate (RMR), energy expenditure (EE), and respiratory quotient (RQ). Eligible studies considered both the chronic and acute intake of GTC-based supplements, with epigallocatechin gallate (EGCG) doses ranging between 100–800 mg. Findings from 15 studies (n = 499 participants) lasting 8–12 weeks (for chronic consumption) or 1–3 days (for acute intake) are summarized. This review reveals the positive effects of GTC supplementation on RQ values (272 subjects). Regarding the effects of acute and chronic GTC supplementation on RMR (244 subjects) and EE (255 subjects), the results did not allow for a definitive conclusion, even though they were promising, because some reported a positive improvement (two studies revealed an increase in RMR: one demonstrated an RMR increase of 43.82 kcal/day and another demonstrated an increase of 260.8 kcal/day, mainly when subjects were also engaged in resistance training exercise). Considering GTC daily dose supplementation, studies in which modifications of energetic parameters occurred, in particular RQ reduction, considered GTC low doses (100–300 mg). GTC may be useful for improving metabolic profiles. Further investigations are needed to better define adequate doses of supplementation.