Glutamine Dipeptide Research Articles

Comment on: Early Enteral Supplementation With Key Pharmaconutrients Improves Sequential Organ Failure Assessment Score in Critically Ill Patients With Sepsis: Outcome of a Randomized, Controlled, Double‐Blind Trial

Objective: To assess the safety and efficacy of an early enteral pharmaconutrition supplement containing glutamine dipeptides, antioxidative vitamins and trace elements, and butyrate in critically ill, septic patients. Design: A prospective, randomized, controlled, double‐blind clinical trial. Setting: Adult intensive care unit in a university hospital. Patients: Fifty‐five critically ill, septic patients requiring enteral feeding. Interventions: Patients received either an enteral supplement (500 ml of Intestamin, Fresenius Kabi) containing conditionally essential nutrients or a control solution via the nasogastric route for up to 10 days. Inclusion occurred within 24 hours of intensive care unit admission. Additionally, patients received enteral feeding with an immunonutrition formula (experimental group) or standard formula (control group) initiated within 48 hours after enrollment. Measurements and main results: Organ dysfunction was assessed by daily total Sequential Organ Failure Assessment (SOFA) score over the 10‐day study period in both patient groups. Patients receiving the experimental supplement showed a significantly faster decline in the regression slopes of delta daily total SOFA score over time compared with control. The difference between the regression coefficients of the 2 slopes was significant irrespective of the level of analysis: intent to treat –0.32 vs –0.14, P < .0001; per protocol– 0.34 vs –0.14, P < .0001; and completers (patients receiving ≥80% of the calculated caloric target over a period of 6 days)– 0.26 vs –0.16, P = .0005. Vitamin C, as a marker of supplement absorption, increased from 10.6 (1.9‐159.4) μmol/L (normal range 20‐50 μmol/L) on day 1 to 58.7 (5.4‐189.9) μmol/L by day 3 (P = .002) in the intervention group but remained below the normal range in the control group 17.0 (2.8‐78.5) on day 1 and 14.3 (2.4‐179.6) on day 3. Serum levels of glycine, serine, arginine, ornithine, vitamin E, and β‐carotene all increased significantly with treatment in the supplementation group. Conclusions: In medical patients with sepsis, early enteral pharmaconutrition with glutamine dipeptides, vitamin C and E, β‐carotene, selenium, zinc, and butyrate in combination with an immunonutrition formula results in significantly faster recovery of organ function compared with control.

The pattern of amino acid exchange across the brain is unaffected by intravenous glutamine supplementation in head trauma patients

Exogenous intravenous glutamine supplementation to head trauma patients leaves intracerebral glutamate concentration unaffected. The effect of an exogenous supply upon glutamine and glutamate exchange across the brain has still not been characterised. A prospective randomised cross-over study, where i.v. glutamine dipeptide was compared with placebo. Arterio-venous concentration differences of free amino acids across the brain and amino acid flux across the leg were measured. In addition, the endogenous glutamine production was calculated. Fifteen mechanically ventilated head trauma patients with GCS < or =8 were included and studied during two consecutive 24-h periods on days 2-5 following head trauma. Glutamine was continuously released from both the brain and the leg. The arterio-venous (a-v) concentration differences over the brain were calculated to be -49+/-26 and -27+/-14 micromol/L during the treatment and control periods respectively, showing a continuous release of glutamine (p<0.0001). On the other hand, the a-v difference of glutamate was not different from zero (p>0.2). The whole-body glutamine rate of appearance (R(a)) was calculated to be 218+/-75micromol/kg body weight/h. Intravenous glutamine supplementation to head trauma patients was associated with an unaffected amino acid exchange pattern across head and leg, without any measurable uptake of glutamate across the brain. Endogenous glutamine production was in the normal range despite the low plasma glutamine concentration. This pilot study opens the possibility to perform prospective clinical trials in head trauma patients to evaluate the clinical efficacy of exogenous glutamine supplementation.

Efficacy of Parenteral Nutrition Supplemented With Glutamine Dipeptide to Decrease Hospital Infections in Critically Ill Surgical Patients

Nosocomial infections are an important cause of morbidity and mortality in the surgical intensive care unit (SICU). Clinical benefits of glutamine-supplemented parenteral nutrition may occur in hospitalized surgical patients, but efficacy data in different surgical subgroups are lacking. The objective was to determine whether glutamine-supplemented parenteral nutrition differentially affects nosocomial infection rates in selected subgroups of SICU patients. This was a double-blind, randomized, controlled study of alanyl-glutamine dipeptide-supplemented parenteral nutrition in SICU patients requiring parenteral nutrition and SICU care after surgery for pancreatic necrosis, cardiac, vascular, or colonic surgery. Subjects (n = 59) received isocaloric/isonitrogenous parenteral nutrition, providing 1.5 g/kg/d standard glutamine-free amino acids (STD-PN) or 1.0 g/kg/d standard amino acids + 0.5 g/kg/d glutamine dipeptide (GLN-PN). Enteral feedings were advanced as tolerated. Nosocomial infections were determined until hospital discharge. Baseline clinical/metabolic data were similar between groups. Plasma glutamine concentrations were low in all groups and were increased by GLN-PN. GLN-PN did not alter infection rates after pancreatic necrosis surgery (17 STD-PN and 15 GLN-PN patients). In nonpancreatic surgery patients (12 STD-PN and 15 GLN-PN), GLN-PN was associated with significantly decreased total nosocomial infections (STD-PN 36 vs GLN-PN 13, P < .030), bloodstream infections (7 vs 0, P < .01), pneumonias (16 vs 6, P < .05), and infections attributed to Staphylococcus aureus (P < .01), fungi, and enteric Gram-negative bacteria (each P < .05). Glutamine dipeptide-supplemented parenteral nutrition did not alter infection rates following pancreatic necrosis surgery but significantly decreased infections in SICU patients after cardiac, vascular, and colonic surgery.

Effect Of Supplementation With Hydrolyzed Whey Protein Enriched With Glutamine Dipeptide On Performance Of Triathletes

Glutamine is a popular dietary supplement consumed for purported ergogenic benefits. Glutamine is the most abundant amino acid found in skeletal muscle and plasma, and it comprises over 60% of the total free amino acid pool. In situations of stress, such as intense exercise, the concentration of glutamine in the blood is decreased. Glutamine supplementation has been reported to enhance protein synthesis as well as improve immune function. PURPOSE: The effect of hydrolyzed whey protein enriched with glutamine dipeptide (Gln) supplementation on performance of triathletes was investigated. METHODS: Nine elite triathletes performed two exhaustive exercise trials in one week interval. Thirty minutes before starting a treadmill exhaustive exercise the subjects ingested 50 g of maltodextrin (placebo) or 50 g of maltodextrin plus 4 tablets of 700 mg of hydrolyzed whey protein enriched with 175 mg of glutamine dipeptide dissolved in 250 mL water. RESULTS: During the test, there was no difference in heart rate (190 ± 9 HR/min) and subjective perception of effort when compared the athletes supplemented or not with Gln. There was no difference in the VO2 max due to the effect of Gln supplementation. On the other hand, the % VO2 max increased when compared Gln supplemented athletes (87.22 ± 4.47 %) with placebo group (79.33 ± 4,3 %). CONCLUSION: Hydrolyzed whey protein enriched with glutamine dipeptide supplementation increased the performance of triathletes during treadmill exhaustive exercise. Suported by FAPESP, CAPES, CnpQ

Effects of exercise on leukocyte death: prevention by hydrolyzed whey protein enriched with glutamine dipeptide

Lymphocyte and neutrophil death induced by exercise and the role of hydrolyzed whey protein enriched with glutamine dipeptide (Gln) supplementation was investigated. Nine triathletes performed two exhaustive exercise trials with a 1-week interval in a randomized, double blind, crossover protocol. Thirty minutes before treadmill exhaustive exercise at variable speeds in an inclination of 1% the subjects ingested 50 g of maltodextrin (placebo) or 50 g of maltodextrin plus 4 tablets of 700 mg of hydrolyzed whey protein enriched with 175 mg of glutamine dipeptide dissolved in 250 mL water. Cell viability, DNA fragmentation, mitochondrial transmembrane potential and production of reactive oxygen species (ROS) were determined in lymphocytes and neutrophils. Exhaustive exercise decreased viable lymphocytes but had no effect on neutrophils. A 2.2-fold increase in the proportion of lymphocytes and neutrophils with depolarized mitochondria was observed after exhaustive exercise. Supplementation of maltodextrin plus Gln (MGln) prevented the loss of lymphocyte membrane integrity and the mitochondrial membrane depolarization induced by exercise. Exercise caused an increase in ROS production by neutrophils, whereas supplementation of MGln had no additional effect. MGln supplementation partially prevented lymphocyte apoptosis induced by exhaustive exercise possibly by a protective effect on mitochondrial function.

Early enteral supplementation with key pharmaconutrients improves Sequential Organ Failure Assessment score in critically ill patients with sepsis: Outcome of a randomized, controlled, double-blind trial*

To assess the safety and efficacy of an early enteral pharmaconutrition supplement containing glutamine dipeptides, antioxidative vitamins and trace elements, and butyrate in critically ill, septic patients. A prospective, randomized, controlled, double-blind clinical trial. Adult intensive care unit in a university hospital. Fifty-five critically ill, septic patients requiring enteral feeding. Patients received either an enteral supplement (500 mL of Intestamin, Fresenius Kabi) containing conditionally essential nutrients or a control solution via the nasogastric route for up to 10 days. Inclusion occurred within 24 hrs of intensive care unit admission. Additionally, patients received enteral feeding with an immunonutrition formula (experimental group) or standard formula (control group) initiated within 48 hrs after enrollment. Organ dysfunction was assessed by daily total Sequential Organ Failure Assessment (SOFA) score over the 10-day study period in both patient groups. Patients receiving the experimental supplement showed a significantly faster decline in the regression slopes of delta daily total SOFA score over time compared with control. The difference between the regression coefficients of the two slopes was significant irrespective of the level of analysis: intent to treat -0.32 vs. -0.14, p < .0001; per protocol -0.34 vs. -0.14, p < .0001; and completers (patients receiving > or = 80% of the calculated caloric target over a period of 6 days), -0.26 vs. -0.16, p = .0005. Vitamin C, as a marker of supplement absorption, increased from 10.6 (1.9-159.4) micromol/L (normal range 20-50 micromol/L) on day 1 to 58.7 (5.4-189.9) micromol/L by day 3 (p = .002) in the intervention group but remained below the normal range in the control group 17.0 (2.8-78.5) on day 1 and 14.3 (2.4-179.6) on day 3. Serum levels of glycine, serine, arginine, ornithine, vitamin E, and beta-carotene all increased significantly with treatment in the supplementation group. In medical patients with sepsis, early enteral pharmaconutrition with glutamine dipeptides, vitamin C and E, beta-carotene, selenium, zinc, and butyrate in combination with an immunonutrition formula results in significantly faster recovery of organ function compared with control.

Optimizing the Dose of Glutamine Dipeptides and Antioxidants in Critically Ill Patients: A Phase I Dose‐Finding Study

Supplementation with glutamine and antioxidants may be associated with an improvement in clinical outcomes, but the optimal dose of these substrates is unknown. The purpose of this study was to determine the safety of high doses of glutamine combined with antioxidants in critically ill patients. We conducted a single-center, open-label, dose-escalating clinical trial. Mechanically ventilated adult patients with clinical evidence of hypoperfusion were sequentially enrolled to 1 of 5 groups. Group 1 (n = 30): no supplementation; group 2 (n = 7): 0.35 g/kg/d of glutamine IV; group 3 (n = 7): same as group 2 plus 15 g/d of glutamine and 150 microg of selenium enterally; group 4 (n = 7): same as group 2 plus 30 g/d of glutamine and 300 microg of selenium enterally; and group 5 (n = 7): same as group 4 plus an additional 500 microg of selenium IV. After enrollment, nutrients were started as soon as possible. All patients were fed enterally according to clinical practice guidelines. The primary outcomes for this study were change in sequential organ function assessment (SOFA) score and safety parameters. Secondary outcomes included whole blood glutathione (GSH), thiobarbituric acid reactive substances (TBARS), and blood cells' mitochondrial DNA/nuclear DNA ratio (RATIO). There were no adverse events attributable to the study nutrients, and the maximum and Delta SOFA did not differ across groups. In group 2, a significant decrease in GSH levels was observed (p = .03). With subsequent groups, the slopes straighten out and the p values are no longer significant, suggesting a greater preservation of GSH levels with escalating doses. In group 2, the slope of the line representing TBARS was horizontal. With subsequent groups, the slopes decrease, and by group 5, this decrease reaches statistical significance (p = .03), suggesting a greater reduction in oxidative stress with the higher doses in group 5. The difference in slopes across all groups describing the mitochondrial RATIO is statistically significant (p = .001), again suggesting that, with higher doses, there is increased mitochondrial function. The doses of glutamine and antioxidants tested in this study seem to be safe and may have positive effects on some mechanistic endpoints. A larger trial will be necessary to confirm their therapeutic effects.

Glutamine Dipeptide Enriched Parenteral Nutrition Significantly Increase Short-Term Survival after HLA-Identical Allogeneic Stem Cell Transplantation.

Sixty-one consecutive patients with hematologic malignancies submitted to HLA-identical sibling allogeneic stem cell transplantation (allo-SCT) were followed in order to evaluate the relationship between the use of glutamine as part of parenteral nutrition (PN) and death/complications related to the procedure. Patients were randomly and blindly assigned to receive either glutamine enriched PN (group 1) or regular PN (group 2). The glutamine dipeptide (Dipeptiven® - Fresenius Kabi) was associated with parenteral nutrition in the first week following transplantation (D0−D+6). Infectious complications, acute GVHD, length of stay (LOS), deaths on D+100 and D+180 and, when possible, intestinal permeability as measured by urinary excretion of lactulosis and mannitol (on admission, D+6 and D+14) were the end-points. Eight patients were excluded from randomization because they refuse to take glutamine or glutamine was not available on D0, but were followed and analyzed as controls, so that group 1 comprised 27 patients and group 2 thirty-four (26+8). Demographics did not differ between groups (age - 37 ± 11 versus 36 ± 8.7, and gender - 14 versus 18 females). Diseases (CML n=37; AML n=12; ALL n=7; MDS n=4; MM n=1) were equally distributed between groups. Patients on group 1 received an average of 23.4g of glutamine/day, corresponding to 49% of the average protein delivery through PN (total 47.9g, against 50 g/day on group2, NS). They were allowed to eat ad libitum. Infection and acute GVHD incidences, and LOS median (36 versus 36.5) were similar on both groups. Intestinal permeability, which showed to be already affected on admission, was not affected by the use of glutamine, but consistently worsened throughout the study, from admission to D+14. Transplant-related mortality (TRM) rate was 29.5% on D+100 (18 deaths, 4 on group 1 and 14 on group 2) and 40.1% on D+180 (25 deaths, 7 on group 1 and 18 on group 2). Survival analysis showed statistical difference on univariate analysis, with a better survival for Group 1 both on D+100 (p= 0.02, log-rank) and D+180 (p=0.02). A Cox regression model was applied using variables that showed a p value of less than 0.2 (diagnosis-related risk, graft source - peripheral blood or bone marrow, conditioning regimen and use of glutamine). Use of glutamine, both on D+100 (HR 6.4; CI95% 1.81–22.44 - p=0.004) and D+180 (HR 4.9; CI95% 1.76–13.61 - p=0.002) was associated with a significantly higher chance of survival. Statistical significance is maintained if the cases excluded from randomization are also excluded from analysis. The results showed that glutamine dipeptide enriched PN plays a role on increasing short-term survival after allo-SCT. Benefits of glutamine dipeptide seems to be independent of mucosal damage/recovery, at least on short term, as intestinal permeability between admission and D +14 was not affected by its use.

Glutamine attenuates TPN-associated liver injury in infant rabbits

The aim of this study was to assess the effects of parenteral alanyl-glutamine dipeptide (Ala-Gln) on TPN-associated liver injury. Forty-three New Zealand rabbits (6-8 days old) were divided into three groups: 12 in the control group (maternal fed); 18 in the TPN group (TPN for 10 days); 13 in the Gln-PN group (TPN+Ala-Gln 400 mg kg(-1) day(-1) for 10 days). At the end of the experiment, liver function and histology were evaluated; MDA content of liver tissues and hepatocyte apoptosis by TUNEL assay were also determined. The serum concentration of direct bilirubin and bile acid in the Gln-PN group was significantly lower than TPN group (P < 0.05), but showed no difference compared with the control group. AST level of the Gln-PN group was lower than the other two groups. The light microscopy (LM) features in the TPN group included cholestasis or diffuse steatosis, while in the Gln-PN group, inflammatory infiltration and mild hydropic degenerative changes were mainly found without obvious cholestasis or proliferation of bile ducts. The electron microscopy appearances corresponded with LM findings. The liver MDA content in the Gln-PN group was clearly lower than the TPN group (P < 0.05), and was lower without statistical significance compared with control group. TUNEL assays showed the ratio of apoptotic hepatocytes in the TPN group was the highest among all the groups (44.59 +/- 6.68 vs. 0.92 +/- 0.85 in the control group, P < 0.01; 44.59 +/- 6.68 vs. 4.14 +/- 2.76 in the Gln-PN group, P < 0.01). There were significantly fewer apoptotic hepatocytes in the Gln-PN group. From this study, we found that glutamine dipeptide supplementation could attenuate TPN-associated liver injury in infant rabbits, and could also decrease liver MDA production and hepatocyte apoptosis during total parenteral nutrition.

The clinical efficacy of glutamine dipeptides on postoperative patients: an updated systematic review of randomized controlled trials from Europe and Asia (1997 - 2005)

To examine the effects of parenteral supplementation of glutamine dipeptide on the outcomes of surgical patients. The relevant data 1997 to March or May 2005 were retrieved from SCI, Medline, EMBASE, Chinese Cochrane Centre databases. The bibliographies of the retrieved papers and the personal file were searched as well. All the patients in the retrieved papers received parenteral nutrition, whether alanyl-glutamine dipeptide (Ala-Gln) was added was the only difference between the intervention and control groups. Methodological quality assessment was based on the Cochrane Reviewers' Handbook and Jadad's Score Scale. Statistical software RevMan4.2 was used for meta-analysis. The data were treated by intention-to-treat method. A total of 1074 relevant papers were screened. Thirteen prospective randomized controlled clinical trials (RCTs) from European & Asian studies met the inclusion criteria. Ten RCTs reported 355 cases of infectious complications showed that Ala-Gln administration significantly reduced the prevalence of infectious complications with a pooled relative risk (RR) of 0.42 (95% CI 0.24 - 0.72; P = 0.002). Eight studies with 273 cases reported the postoperative length of stay (LOS) and showed that Ala-Gln significantly reduced the postoperative LOS by 3.25 days (95% CI = -4.87 to -1.62; P = 0.00009). There was no significant effect of Ala-Gln on cost of hospitalization, though there was a trend to reduction (2 studies, pooled n = 52, P = 0.2). Parenteral Ala-Gln significantly reduces the post-operative infectious morbidity and LOS among surgical patients.

Route of administration (enteral or parenteral) affects the contribution of l-glutamine to de novo l-arginine synthesis in mice: a stable-isotope study

A pathway from enteral L-glutamine as substrate for L-arginine synthesis is suggested by previous studies. L-Glutamine and L-glutamine dipeptides exhibit numerous beneficial effects in experimental and clinical studies. In trauma patients, enteral L-glutamine supply increased plasma L-arginine. The present study was designed to quantify the contribution of L-glutamine to the de novo L-citrulline and L-arginine synthesis in mice when L-glutamine is administered in a high dose of labeled L-glutamine or L-alanyl-L-glutamine by the enteral or parenteral route. For this purpose, male Swiss mice (n = 43) underwent a laparotomy, and catheters were inserted for sampling and infusion. A primed, constant, and continuous infusion of L-alanyl-L-[2-(15)N]glutamine (dipeptide groups) or L-[2-(15)N]glutamine (free L-glutamine groups), simultaneously with L-[ureido-(13)C,(2)H(2)]citrulline and L-[guanidino-(15)N(2),(2)H(2)]arginine, was given (steady-state model). Mice received the L-glutamine tracers intravenously (jugular vein) or enterally (duodenum). Enrichments of metabolites were measured by LC-MS. Arterial L-glutamine concentrations were the highest in the intravenous dipeptide group. L-Glutamine was converted to L-citrulline and L-arginine when L-[2-(15)N]glutamine and L-alanyl-L-[2-(15)N]glutamine were given by enteral or parenteral route. The contribution of L-glutamine to the de novo synthesis of L-citrulline and L-arginine was higher in the enteral groups when compared with the intravenous groups (P < 0.005). Therefore, the route of administration (enteral or parenteral) affects the contribution of L-glutamine, provided as free molecule or dipeptide, to the de novo synthesis of L-arginine in mice.

CONFORMATION AND PHASE TRANSITION OF POLY-GLUTAMINE

In order to provide insights into the misfolding mechanism and the subsequent aggregate formation which cause what are known as the neurodegenerative polyglutamine diseases, we have simulated a 10-residue polyglutamine (poly-Q) chain in vacuum and in solvent by multicanonical method, which enabled us to study the system in a wide temperature range and discuss thermodynamic properties. It is understood that the system in vacuum shows two phase transitions, first of them occur at high temperature that is the well-known helix-coil transition and the second one is a solid-solid transition. However, the poly-Q chain in solvent is in a random coil state at higher temperatures, goes through a conformational change at T = 200 K and assumes predominantly a mixture of anti-parallel β-sheet and α-helix structures at low temperatures. One-residue glutamine dipeptide is also simulated and low-energy stable conformations are identified.

Glutamine dipeptide for parenteral nutrition in abdominal surgery: A meta-analysis of randomized controlled trials

To assess the clinical and economical validity of glutamine dipeptide supplemented to parenteral nutrition (PN) in patients undergoing abdominal surgery. A meta-analysis of all the relevant randomized controlled trials (RCTs) was performed. The trials compared the standard PN and PN supplemented with glutamine dipeptide in abdominal surgery. RCTs were identified from the following electronic databases: the Cochrane Library, MEDLINE, EMBASE and ISI web of knowledge (SCI). The search was undertaken in April 2006. Literature references were checked by computer or hand at the same time. Clinical trials were extracted and evaluated by two reviewers independently. Statistical analysis was performed by RevMan4.2 software from Cochrane Collaboration. A P value of < 0.05 was considered statistically significant. Nine RCTs involving 373 patients were included. The combined results showed that glutamine dipeptide has a positive effect in improving postoperative cumulative nitrogen balance (weighted mean difference (WMD = 8.35, 95% CI [2.98, 13.71], P = 0.002), decreasing postoperative infectious morbidity (OR = 0.24, 95% CI [0.06, 0.93], P = 0.04), shortening the length of hospital stay (WMD= -3.55, 95% CI [-5.26, -1.84], P < 0.00001). No serious adverse effects were found. Postoperative PN supplemented with glutamine dipeptide is effective and safe to decrease the infectious rate, reduce the length of hospital stay and improve nitrogen balance in patients undergoing abdominal surgery. Further high quality trials in children and severe patients are required, and mortality and hospital cost should be considered in future RCTs with sufficient size and rigorous design.

Effects of L-alanyl-glutamine upon the blood and kidney biochemical parameters in the rat hind limb model of ischemia/reperfusion

To investigate the effects of l-alanyl-glutamine (Ala-Gln) intragastric administration upon blood and kidney metabolic parameters alterations in rats subjected to ischemia/reperfusion of hind limb. Forty-eight male rats were randomized in 2 groups offered via gavage either saline 2.0 mL (G-1) or Ala-Gln solution 0.75 mgKg-1(G-2) once a day at 7 AM during 7 days. One-hour after the last gavage (Day 7) all rats were submitted to ether anesthesia, laparotomy and clamping of the left iliac artery for 3 h. Kidney and blood samples were collected at the end of ischemic period (3 h) and at 1-3-6 h during reperfusion period for metabolites (pyruvate, lactate, glucose and ketone bodies) enzymatic analysis. ATP was also assayed in kidney samples. Lactacemia and ketonemia were significantly increased in Ala-Gln treated rats during reperfusion. Kidney pyruvate concentrations were significantly decreased and tissue lactate concentrations were significantly increased during reperfusion (1 h and 3 h) in G-2 rats compared with respective controls. Glucose, ATP and ketone bodies concentrations were significantly increased in the kidney in L-Ala-Gln treated rats at 3 hours after reperfusion as compared to respective controls. Unilateral hind limb ischemia in L-Ala-Gln pre-treated rats may induce increased lactacemia and increased kidney lactate concentrations, indicating increased glycolytic activity in renal medulla and in other peripheral tissues. Higher ketonemia during reperfusion may reflect a possible increase in ketogenesis due to lower insulin plasma concentration hepatic signaling as a result of increased glucose oxidation in peripheral tissues, caused by the intra-gastric administration of glutamine dipeptide, suggesting also decreased insulin resistance.

Effects on glutathione of patients received glutamine dipeptide enriched parenteral nutrition post abdominal surgery

To observe the effects of glutamine (GLN) enriched parenteral nutrition (PN) on glutathione level, immune function, liver function, infectious complication and hospital stay of patients undergone abdominal operation. Forty patients with abdominal surgical disease undergoing elective surgical treatment were randomly divided into two groups (study and control group). All patients received total parenteral nutrition (TPN) for up to 7 days perioperatively. The control group received TPN while the study group received TPN including GLN dipeptide. Both groups received isonitrogen and isocaloric nutrition. Nonprotein caloric intake is 83.6 kJ.kg(-1).day(-1), glycogen: lipid ratio is 7:5, nitrogen intake is 0.16 g.kg(-1).d(-1), calories:nitrogen ratio is 489 kJ:1 g. The decreasing degree of glutathione levels of plasma and red blood cell in study group is lower than that in control group postoperatively. GSH/GSSG ratio of plasma in study group is higher than that in control group on 3rd day postoperatively (53 +/- 11 vs 31 +/- 7, F = 4.725, P = 0.001). Albumin (ALB) of both groups decreased slightly postoperatively. ALB level of study group was higher than that of control group on 3rd day postoperatively [(3.8 +/- 0.4) g.dl(-1) vs (3.4 +/- 0.4) g.dl(-1), F = 2.128, P = 0.02]. No significant differences were noted between immunoglobin (IgG, IgM and IgA) and T lymphocyte subgroup (CD4, CD8, CD4/CD8) levels of both groups postoperatively. There was no infectious complication in study group, while one in control group. There was shorten trend of hospital stay in study group compared with control group [(22.3 +/- 2.1) d vs (24.9 +/- 1.7) d, t = -0.935, P = 0.32]. Glutamine enriched PN has the trend of maintaining glutathione level of plasma and red blood cell in patients having undergone abdominal operation, and can sustain GSH/GSSG ratio and ALB level, protect antioxidant ability, promote liver function postoperatively. Glutamine enriched PN has the trend of shortening hospital stay, decreasing incidence of infectious complication.

Effects of Parenteral Nutrition Supplemented with Alanyl‐Glutamine on Nutrition Status in Rats

Glutamine, a nonessential amino acid, has received increasing attention because it becomes essential during stress and catabolic conditions. Many investigations have shown that during severe stress, the consumption of glutamine exceeds glutamine synthesis, resulting in depletion of glutamine stores. The aim of this study was to evaluate the effects of supplementing parenteral diets with a glutamine-containing dipeptide, L-alanyl-L-glutamine, on rat nutrition status. Male Wistar rats were used. Animals (n = 36) were centrally catheterized and randomly assigned to 1 of the following groups based on method of parenteral nutrition (PN): control group with oral nutrition and IV infusion of a saline solution; standard parenteral nutrition (SPN) group; or alanyl-glutamine-supplemented PN (ALA-GLN PN) group (20 g/L). Parenteral nutrition was isocaloric and isonitrogenous. Infusions were administered at a rate of 2.0 mL/h over 5 days. Nutrition status was assessed by body weight change, plasma proteins, accumulated urinary creatinine, and nitrogen balance. Accumulated urinary creatinine increased significantly after day 4 in the ALA-GLN PN group, compared with the SPN group and the controls. Body weight change significantly differed on day 5 between the ALA-GLN PN and SPN groups. After 3 days, nitrogen balance was significantly lower and nitrogen retention higher in the ALA-GLN PN group when compared with the SPN group. Albumin and transferrin concentrations decreased significantly in the SPN group, but did not differ from the controls in the ALA-GLN PN group. Weight, plasma proteins, urinary accumulated creatinine, and nitrogen retention showed a better evolution in the group supplemented with the glutamine dipeptide when compared with the SPN group. Our results suggest a more suitable nutrition support in animals receiving L-alanyl-L-glutamine.

Intestinal renal metabolism ofl-citrulline andl-arginine following enteral or parenteral infusion ofl-alanyl-l-[2,15N]glutamine orl-[2,15N]glutamine in mice

Previously, we observed increased plasma arginine (ARG) concentrations after glutamine (GLN)-enriched diets, in combination with clinical benefits. GLN delivers nitrogen for ARG synthesis, and the present study was designed to quantify the interorgan relationship of exogenous L-GLN or GLN dipeptide, by enteral or parenteral route, contributing to intestinal citrulline (CIT) and renal de novo ARG synthesis in mice. To study this, we used a multicatheterized mouse model with Swiss mice (n = 43) in the postabsorptive state. Stable isotopes were infused into the jugular vein or into the duodenum {per group either free L-[2,(15)N]GLN or dipeptide L-ALA-L-[2,(15)N]GLN, all with L-[ureido-(13)C-(2)H(2)]CIT and L-[guanidino-(15)N(2)-(2)H(2)]ARG} to establish renal and intestinal ARG and CIT metabolism. Blood flow was measured using (14)C-para-aminohippuric acid. Net intestinal CIT release, renal uptake of CIT, and net renal ARG efflux was found, as assessed by arteriovenous flux measurements. Quantitatively, more de novo L-[2,(15)N]CIT was produced when free L-[2,(15)N]GLN was given than when L-ALA-L-[2,(15)N]GLN was given, whereas renal de novo L-[2,(15)N]ARG was similar in all groups. In conclusion, the intestinal-renal axis is hereby proven in mice in that L-[2,(15)N]GLN or dipeptide were both converted into de novo renal L-[2,(15)N]ARG; however, not all was derived from intestinal L-[2,(15)N]CIT production. In this model, the feeding route and form of GLN did not influence de novo renal ARG production derived from GLN.

Safety and intestinal tolerance of high-dose enteral antioxidants and glutamine peptides after upper gastrointestinal surgery

Safety and intestinal tolerance of an early high-dose enteral administration of antioxidative vitamins, trace elements, and glutamine dipeptides. open intervention trial. Two university teaching hospitals. A total of 14 patients requiring jejunal feeding (64+/-14 y). A measure of 500 ml/day Intestamin (FreseniusKabi: 250 kcal/1.050 kJ, 300 microg selenium, 20 mg zinc, 400 mug chromium, 1500 mg vitamin C, 500 mg vitamin E, 10 mg beta-carotene, 30 g glutamine) for 5 days beginning 6 h after surgery. Parenteral/enteral nutrition was provided to achieve energy target (25 kcal/kg/day). Intestinal complaints, plasma nutrients, and glutathione. Only minor signs of nausea, hiccups, flatulence (3/14). Plasma micronutrients (except beta-carotene) postoperatively decreased and increased to normal on day 5. Extracellular glutamine remained low (preop: 520+/-94; d1: 357+/-67; d5: 389+/-79 micromol/l); total glutathione decreased (d1: 9.4+/-3.8; d5: 3.6+/-2.5 micromol/l). Study feed is well tolerated and metabolically safe representing a valuable tool for targeted pharmaconutrient supply.

Perioperative administration of parenteral fish oil supplements in a routine clinical setting improves patient outcome after major abdominal surgery

Background & aims: It is hypothesized that provision of pre- and/or postoperative omega-3 fatty acids to surgical patients in clinical routine improves clinical outcome. Methods: Retrospective evaluation of a 2-year-longitudinal data base of ICU patients (n=249) elected for major abdominal surgery. Group I (n=110): postoperative standard parenteral nutrition (1.2g amino acids, 0.3g glutamine dipeptide, 0.6g lipids, 4g/kg glucose; energy ratio glucose to lipid 2:1); group II (n=86): part of postoperative lipid emulsion replaced by fish oil; group III (n=53): in addition 2–3 days preoperative fish oil supplementation (max. 100ml/d). Results: A decrease in mortality was observed in group III compared to group I (P=0.02). The number of patients requiring mechanical ventilation was lower with perioperative fish oil (n=34 in groups I and II. 10 in III, P<0.05). The number of days in ICU was not different (group I: 7.6 days, group II: 7.0, group III: 7.3), the length of hospital stay was shorter in group I (group I: 29.2 days, group II: 24.9, group III: 22.2, P<0.05 vs I). Conclusions: In a retrospective evaluation, perioperative provision of parenteral fish oil (ca. 10g/day) beneficially influences patient outcome probably by modulating the immune response.

The effects of supplemental glutamine dipeptide on gut integrity and clinical outcome after major escharectomy in severe burns: a randomized, double-blind, controlled clinical trial

Summary Objective : To evaluate the effects of glutamine dipeptides on gut permeability, plasma endotoxin and outcome variables following extensive eschar excision on severe burns. Methods : Thirty patients with severe burns (total body surface burns, 30–50% and third degree burns, 15–25%) were investigated in a prospective, randomized, double-blind clinical trial, to receive parenteral nutrition with (test group) or without (control group) glutamine dipeptide supplementation. Protocol was approved by the local ethical committee and the informed consents were obtained. Parenteral iso-energetic and iso-nitrogenous nutrition was initiated on postoperative day 1 (POD+1) and was administered to both groups until postoperative day 12 (POD+12). Glutamine dipeptide supplement (Dipeptiven ® , Fresenius Kabi, Bad Homburg, Germany) corresponded to 0.5g/kg bw/d (equal to 0.35g glutamine kg bw/d). Plasma glutamine (gln-p), serum endotoxin concentrations, and the lactulose/mannitol absorption ratio (L/M, which reflects gut permeability) were measured throughout the clinical course. Survival rate of skin graft, wound healing time and infection rate were assessed and length of hospital stay and total costs were determined at discharge. Results : The concentrations of gln-p remained low in the control group, but increased in the supplemented group (POD+1: control, 321±40μmol/l, vs. test 431±52μmol/l, P 0.001 ; POD+12: control, 397±38μmol/l, vs. test 532.1±48.9μmol/l, P 0.001 ). L/M ratio was initially increased in both groups, reflecting enhanced intestinal permeability; the levels being normalized at POD+12. Endotoxin levels were equally elevated in both groups at commencement (POD+1), but decreased significantly in patients receiving gln (POD+12: control, 0.141±0.045 vs. test 0.112±0.026, P 0.043 ). Wound healing time was significantly shorter in the gln group compared to controls (32±3 days vs. 37±6, P 0.012 ). Infection rate revealed an obviously lower tendency (control: 26% vs. test 13% NS), yet without approaching a significant difference. Total cost of hospitalization was 45.300±5.500 RMB (about 5500 US$) in controls vs. 41.400±3.400 RMB (about 5000 US$) in the gln group, P 0.029 ; although it should be emphasized that the cost of glutamine supplementation was accounted for in the calculation. The skin graft survival rate and length of hospital stay were not significantly different between the groups. Conclusion : Supplementation with glutamine dipeptide was associated with enhanced gln plasma concentrations, decreased gut permeability and endotoxin levels as well as wound healing time and lower cost of hospitalization.