Enteral Glutamine Supplementation Research Articles

Effectiveness of glutamine and arginine in wound healing of pressure ulcers: A systematic review protocol

IntroductionVarious nutrients play a physiological role in the healing process of pressure ulcers (PUs). Nutritional interventions include the administration of enteral nutritional supplements and formulas containing arginine, glutamine, and micronutrients. The aim of this systematic review is to evaluate the effectiveness of enteral nutritional supplements and formulas containing arginine and glutamine on wound-related outcomes. These include (1) time to healing, (2) changes in wound size, (3) local wound infection, (4) PU recurrence, and (5) PU-related pain. Materials and methodsThis protocol was developed according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). A search will be conducted in the Cochrane Library, EMBASE, PubMed (MEDLINE), CINAHL (EBSCOhost interface) and Web of Science. In addition, a manual search will be conducted to identify relevant records. Except for systematic reviews, no restrictions will be placed on the study design, the population studied or the setting. Studies that do not address PUs, in vitro studies and studies that do not report wound-related outcomes will be excluded. Study selection, risk of bias assessment and data extraction will be performed independently by three researchers. Depending on the extent of heterogeneity of interventions, follow-up time and populations, results will be summarised either by meta-analysis or narrative synthesis. ConclusionsThis is the first systematic review to identify, evaluate and summarise the current evidence for enteral arginine and glutamine supplementation on wound-related outcomes in PUs. The review will provide a solid basis for deriving valid and clinically relevant conclusions in this area.

Glutamine enteral therapy for critically ill adult patients: An updated meta-analysis of randomized controlled trials and trial sequential analysis

BackgroundThe efficacy of supplemental enteral glutamine (GLN) in critical illness patients remains uncertainty. ObjectiveBased on a recently published large-scale randomized controlled trials (RCTs) as regards the use of enteral GLN, we updated a meta-analysis of RCTs for further investigating the effects of enteral GLN administration in critically ill patients. MethodsWe searched RCTs reporting the impact of supplemental enteral GLN about clinical outcomes in adult critical illness patients from EMBASE, PubMed, Clinical Trials.gov, Scopus and Web of Science and subsequently registered the protocol in the PROSPERO (CRD42023399770). RCTs of combined enteral-parenteral GLN or parenteral GLN only were excluded. Hospital mortality was designated as the primary outcome. We conducted subgroup analyses of primary outcome based on specific patient populations, dosages and therapy regimens, and further performed trial sequential analysis (TSA) for clinical outcomes. ResultsEighteen RCTs involving 2552 adult critically ill patients were identified. There were no remarkable influences on hospital mortality regardless of different subgroups (OR, 1.05; 95% CI, 0.85 – 1.30; p = 0.67), intensive care unit (ICU) length of stay (LOS) (MD, -0.07; 95% CI, -1.12 – 0.98; p = 0.89) and infectious complications (OR, 0.90; 95% CI, 0.75 – 1.10; p = 0.31) with enteral GLN supplementation. Additionally, the results of hospital mortality were confirmed by TSA. However, enteral GLN therapy was related to a reduction of hospital LOS (MD, -2.85; 95% CI, -5.27 – -0.43; p = 0.02). ConclusionsIn this meta-analysis, it seems that enteral GLN supplementation is unlikely ameliorate clinical outcomes in critical illness patients except for the reduction of hospital LOS. Our data do not support enteral GLN supplementation used routinely in critical illness patients.

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

Role of Early Enteral Glutamine Supplementation in Reducing Infectious Morbidity in Burn Patients: A Case-Control Study

Severe burn injury is more challenging to sustain life than a preburn status. The situation changes drastically in terms of energy demands/ expenditure and the great degree of susceptibility to infections due to the loss of amino acids. Glutamine stimulates the immune system and prevents catabolism. The bacterial translocation from the gut can be decreased by glutamine supplementation, thereby suppressing the inflammatory response. In acute burn injury, plasma and muscle glutamine depletion is observed to contribute to muscle wasting, weight loss, and infection. Patients with 20%–50% TBSA burns presenting within 24 hours of injury to the emergency department or outpatient department were included in the study. The patients were divided into two groups randomly. In group 1 (Cases), all patients were given enteral glutamine supplementation at the dose of 0.5 mg/kg/day either orally or through a nasogastric tube started within 24 hours of injury. Group 2 (Control) had all the patients in whom enteral glutamine supplementation was not given. In both groups, blood analysis for total leucocyte count (TLC) and total serum proteins (TSP) was done upon admission. On Day 4, followed by analysis every fourth day, after that, till healing occurred or the patient was taken up for grafting. Blood and wound swab cultures were done on the third day of admission, then the first week, followed by weekly cultures for 4 weeks or till healing occurred or the patient was taken up for grafting. A total of 123 patients were studied. There was a decreasing trend in the mean values of the TLC and an increasing trend in TSP in both groups. The difference became statistically significant from Day 20 onwards. The pattern of wound cultures was found to be statistically significant in Week 3 and Week 4, whereas the difference in blood culture positivity among the groups was statistically significant in Week 3. We noted, in our study, that the glutamine supplementation to the early enteral nutrition increased the TSP levels and decreased the TLC, wound, and blood culture positivity rates in the study group. Glutamine supplementation can contribute to improved immunity and reduce burn wound sepsis and bacteremia. All these combined can lead to decreased morbidity, improved wound healing, and better outcomes with lesser costs.

Enteral Glutamine Supplementation is Associated with Lowering Wound Infection Morbidity and Length of Hospital Stay among Burn Patients: A Meta-analysis and Systematic Review

Background. Significant nutritional support to meet increased energy expenditure is vital for burn patient's survival. Burn injury may lead to a significant decrease in Glutamine levels, which inspired the hypothesis that glutamine supplementation following burn injury would improve outcomes. Hence, the purpose of this meta-analysis study was to provide the rationale for determining the efficacy and safety of enteral glutamine in burn patients.
 
 Methods. We conducted a meta-analysis based on PRISMA design to assess the potency of enteral glutamine supplementation as adjuvant treatment in patients with burn trauma. PubMed, Sciencedirect, and Google scholar were searched systematically using the following keywords: "enteral glutamine" and "burn patients" and "critical ill" and "infection" and "length of stay". Newcastle-Ottawa Scale (NOS) was used to assess the quality of papers included in our meta-analysis. A Z test was used to determine the significance of pooled effect estimates. Publication bias was assessed using Egger's. We used Comprehensive Meta-Analysis (CMA) version 2.1 to analyze the data.
 
 Results: A total of 12 studies recording 344 cases and 335 controls were enrolled for our analysis. Data on hospital Length of Stay (LOS) was found that enteral glutamine supplementation provided a significant result in reducing the LOS (Std mean diff: 0.70, 95%CI: 0.16 – 1.24; p=0.0100). We also found that a higher risk of positive wound culture was significantly observed in patients without the supplementation of enteral glutamine (OR 2.15, 95% CI: 1.41 – 3.27; p=0.0003) compared to patients receiving enteral glutamine supplementation among burn patients.
 
 Conclusion: In our meta-analysis study, enteral glutamine in burn patients confers significantly shorter LOS and lower risk of wound infection among burn patients. We suggest that enteral glutamine supplementation may be a beneficial intervention for the management of burn patients.

Early enteral nutrition with L-glutamine improves anastomotic healing in rats administered hyperthermic intraperitoneal chemotherapy with cisplatin and 5-FU

Background/Aim: One of the most significant aspects of intestinal surgery is anastomotic wound healing. After intestinal surgery, the most serious complication is gastrointestinal leakage, which is associated with a high rate of morbidity and mortality. The rate of morbidity and mortality can be reduced by increasing the mechanical resistance of the anastomosis. Glutamine improves impaired wound healing through effects on the healing process. This study investigated the effects of early enteral glutamine supplementation on colonic anastomosis healing in rats treated with hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin and fluorouracil (5-FU). Methods: Twenty-four rats were divided into three groups. Group 1 underwent colonic anastomosis and intraabdominal hyperthermic saline administration, Group 2 underwent colonic anastomosis and HIPEC, and Group 3 underwent colonic anastomosis and HIPEC and postoperative administration of glutamine solution via an orogastric tube for 7 days. On day 7, all rats were sacrificed and anastomotic bursting pressure (ABP) was evaluated. Tissue specimens were taken to examine tissue hydroxyproline levels and histopathological changes in the anastomotic line. Results: The ABP was significantly greater in Group 2 than in Groups 1 and 3 (P=0.001 and P=0.046, respectively). The tissue hydroxyproline level was higher in Group 1 and Group 3 than in Group 2 (P=0.001 and P=0.043, respectively). The histopathological findings in Group 3 were better than those in Group 2. The histopathological findings were observed to improve in the early enteral nutrition with Glutamine group. Conclusions: The findings of this study indicate that early enteral glutamine supplementation facilitates colonic anastomosis healing following HIPEC with cisplatin and 5-FU, by increasing the ABP and tissue concentrations of hydroxyproline and decreasing the inflammatory response.

Effects of enteral glutamine supplementation on intestinal permeability in acute pancreatitis: A literature review

Background. Glutamine has been shown to improve the gut mucosal barrier. However, the evidence for benefit of enteral glutamine on intestinal permeability in acute pancreatitis (AP) is limited.
 Objective. To identify the effect of enteral glutamine supplementation on intestinal permeability in patients with AP.
 Method. A systematic search was conducted by extracting evidence from published studies on enteral glutamine supplementation in three databases (PubMed, Cochrane Central Register of Controlled Trials, and SciElo) relevant to AP from 1 January 2010 till 31 December 2020. Outcomes assessed were intestinal permeability, infectious complication, hospital length of stay, and mortality rate.
 Results. A total of 6 studies found by search, in which 2 human RCTs with 7 days duration of intervention with 1b-1c quality based on Criteria by Center of Evidence-Based Medicine, University of Oxford. Both studies showed the benefit of early enteral glutamine supplementation on intestinal permeability in patients with AP.
 Conclusions. Enteral glutamine supplementation has been shown to improve the gut mucosal barrier in AP. Despite its significant improvement in intestinal permeability, glutamine supplementation did not display a consistently positive effect on clinical outcomes.

Effects of early enteral glutamine supplementation on the outcome of severe burns: A randomized control study

Context: Burns is a condition associated with high mortality and morbidity. Nutrition plays an important role in the recovery of these patients. Amino acid glutamine is an important energy substrate for immune cells and for the intestinal epithelium. Glutamine is the preferred respiratory fuel for both lymphocytes and enterocytes. It stimulates the immune system and prevents catabolism. Aim: This study is aimed at determining if oral supplementation of glutamine can improve the outcome in patients with severe burns. Materials and Methods: It is a randomized controlled study. Patients of severe burns (30%–50%) were randomized into two groups. The first group was started on enteral nutrition but without glutamine supplementation. The second group received enteral nutrition with glutamine supplementation. All patients were followed up for a period of 1 month from the day of burns. Blood culture, wound culture, blood counts, and serum total proteins were done once every week for all patients. Statistical Analysis: Student's t-test was used to analyze the quantitative and Chi-square test was used to measure the qualitative data. Results: One hundred and two patients were included in the study, of which 49 were in Group 1 and 53 patients in Group 2. The mean percentage of burns in the two groups was comparable at 40.71% and 41.72%, respectively. Total leukocyte counts, mean duration of hospital stay, and mortality rates did not show any statistically significant difference between the two groups. However, serum protein levels showed a significant increase in the glutamine-supplemented group from the 3rd week onward. Wound infection rates were also lower in the glutamine-supplemented group, i.e., 19.5% vs. 2.1% by the 4th week. Conclusion: Glutamine supplementation has shown to enhance serum protein levels and hence improve nutritional status of these patients. It is also useful for its immunomodulatory effects, thus reducing burn wound infection, as shown by lesser number of burn wound culture positivity rates.

The Effect of Glutamine Supplementation on Microbial Invasion in Surgical Infants Requiring Parenteral Nutrition: Results of a Randomized Controlled Trial.

To determine whether parenteral plus enteral glutamine supplementation influences microbial invasion in surgical infants who require parenteral nutrition (PN). An prospective double-blind randomized controlled trial studying surgical infants receiving PN for at least 5days for congenital or acquired intestinal anomalies (2009-2012) was used. Infants were randomized to receive either glutamine supplementation (parenteral plus enteral; total 400mg/kg/d) or isonitrogenous control. The primary end point was microbial invasion evaluated after 5days of supplementation and defined as: (i) positive conventional blood culture, (ii) evidence of microbial DNA in blood (polymerase chain reaction), (iii) plasma endotoxin level ≥50 pg/mL, or (iv) plasma level of lipopolysaccharide binding protein ≥50 ng/mL. Data are given as median (range) and compared by logistic regression. Sixty infants were randomized and reached the primary end point. Twenty-five patients had intestinal obstruction, 19 had abdominal wall defects, and 13 had necrotizing enterocolitis. Thirty-six infants showed evidence of microbial invasion during the study, and 17 of these were not detected by conventional blood culture. There was no significant difference between the 2 groups in the primary outcome; evidence of microbial invasion after 5days was found in 9/31 (control group) and 8/29 (glutamine group) (odds ratio 0.83 [0.24-2.86; P=0.77]). More than half of surgical infants requiring PN showed evidence of microbial invasion. Approximately half of this was not detectable by conventional blood cultures. Parenteral plus enteral glutamine supplementation had no effect on incidence of microbial invasion.

Efficacy of enteral glutamine supplementation in patients with severe andpredicted severe acute pancreatitis- Arandomized controlled trial.

In severe acute pancreatitis (AP), intravenous glutamine has been shown to reduce the rate of complications, hospital stay, and mortality. In the present randomized trial, we aimed to evaluate the effect of enteral glutamine supplementation on clinical outcomes, gut permeability, systemic inflammation, oxidative stress, and plasma glutamine levels in patients with severe and predicted severe AP. Patients with AP admitted within 72h of onset of symptoms were included. The primary outcome measurewas development of infected pancreatic and peri-pancreaticnecrosis and in-hospital mortality. High-sensitivity C-reactive protein (HS-CRP) and interleukin-6 (IL-6) were evaluated as markers of inflammation; plasma thiobarbituric acid reactive substances (TBARS) and activities of serum superoxide dismutase and glutathione peroxidase were determined to evaluate oxidative stress; serum polyethylene glycol (PEG) was tested for intestinal permeability; subjective global assessment (SGA) was used for nutritional assessment, and an improvement in organ function was measured by the Modified Marshall score. Intention-to-treat analysis was used. Ap-value of < 0.05 was considered statistically significant. After power calculation, we enrolled 18 patients in the glutamine and 22 in the control arm. There was no significant improvement in the development of infected necrosis and in-hospital mortality between the groups. Improvement in Modified Marshall score was observed in a higher proportion of patients receiving glutamine (15 [83.3%] vs. 12 [54.5%]; p = 0.05). Plasma glutamine levels improved more in glutamine-treated group (432.72 ± 307.83 vs. 618.06 ± 543.29μM/L; p = 0.004), while it was lower in controls (576.90 ± 477.97 vs. 528.20 ± 410.45μM/L; p = 0.003). PEG level was lower after glutamine supplementation (39.91 ± 11.97 vs. 32.30 ± 7.39ng/mL; p = 0.02). Statistically significant reduction in IL-6 concentration was observed in the glutamine group at the end of treatment (87.44 ± 7.1 vs. 63.42 ± 33.7μM/L; p = 0.02). Despite absence of improvement in infected necrosis and in-hospital mortality, enteral glutamine supplementation showed improvement in gut permeability, oxidative stress, and a trend towards improvement in organ function as depicted by improvement in the Modified Marshall score. NCT01503320.

Effect of enteral glutamine supplementation for low-birth-weight infants on weight gain patterns and levels of fecal secretory immunoglobulin A.

Glutamine is needed for optimal cell growth and for the immune system, especially in the enterocytes of gut mucosal immune responses. Low birth weight makes infants susceptible to glutamine depletion because nutrition is limited in the first week of life. To determine the effect of enteral glutamine supplementation on weight gain patterns and fecal secretory immunoglobulin A. This study is a double-blind, randomized controlled trial. Infants were randomly assigned to the glutamine group and placebo group. The glutamine group was supplemented with glutamine 400 mg/kg/day for 14 days, and placebo group received glucose 400 mg/kg/day for 14 days. The infants were observed for 30 days. Return-to-birth-weight, weight gain velocity, and fecal secretory immunoglobulin A levels were monitored during the study. Thirty-seven low-birth-weight infants were randomly assigned to the glutamine and placebo groups. The glutamine group had a shorter return-to-birth-weight time than the placebo group (8.1±0.9 vs. 11.0±1.6 days) and faster weight gain velocity (20.0±1.8 vs. 15.5±2.2 g/kg/day) (p<0.001). Secretory immunoglobulin A levels after glutamine supplementation were higher than in the placebo group (0.456±0.057 vs. 0.376±0.035 mg/g) (p<0.001). Levels of secretory immunoglobulin A after treatment in each group were increased. However, there was a significant difference before and after supplementation between the glutamine and placebo groups (0.247±0.024 vs. 0.140±0.016 mg/g) (p<0.001). Enteral glutamine supplementation in low-birth-weight infants accelerates return to birth weight, increases the weight gain velocity, and the levels of fecal secretory immunoglobulin A.

Effects of Early Enteral Glutamine Supplementation on Intestinal Permeability in Critically Ill Patients

ABSTRACTBackground and aimsEnteral administration of glutamine has been proposed as an effective recovery of intestinal barrier function. This amino acid has a modulating effect on the reducing bacterial translocation, which can influence immune functions of the intestine. The objective was to evaluate the effects of early enteral glutamine supplementation on intestinal permeability in critically ill patients.Materials and methodsA total of 80 critically ill patients older than 18 years were randomly assigned to one of two groups according to the stratified blocked randomization by age and admission category. Consecutive participants took enteral formula plus 0.3 g/kg/day glutamine powder or enteral formula plus maltodextrin during the ICU stay for a maximum of 10 days. Plasma glutamine, endotoxin, zonulin, and antiendotoxin immunoglobulin (Ig)G/IgM concentrations were measured on days 5 and 10 of intervention.ResultsOut of 80 participants, 36 patients in the glutamine group and 34 patients in the control group were included in the analysis of the outcomes. Enteral glutamine significantly reduced plasma zonulin concentration up to 40% during 10 days. This reduction was significantly greater compared with that of the placebo group (p<0.001). Endotoxin concentration decreased in both groups; this reduction was significantly greater in the glutamine group (p = 0.014). The antiendotoxin IgM and IgG antibody levels increased in the glutamine group but decreased in the control group (p <0.001). There were no significant differences in clinical outcomes between two groups.ConclusionEarly enteral glutamine supplementation led to a declined intestinal permeability in critically ill patients.How to cite this articleShariatpanahi ZV, Eslamian G, Ardehali SH, Baghestani AR. Effects of Early Enteral Glutamine Supplementation on Intestinal Permeability in Critically Ill Patients. Indian J Crit Care Med 2019;23(8):356–362.

Combined Enteral and Parenteral Glutamine Supplementation in Endotoxemic Swine: Effects on Portal and Systemic Circulation Levels

Objective: To measure plasma glutamine (GLN) levels in systemic and portal circulation after combined enteral and parenteral administration in early endotoxemic swine. We hypothesized that this combination will be more efficient than intravenous administration alone in restoring plasma levels during the course of endotoxemia. Materials and Methods: Endotoxemia was induced with Escherichia coli O111:B4 lipopolysaccharide (LPS) (250 μg/kg body weight) in 16 anes­thetized, fasted swine and maintained by constant infusion (2 μg/kg/h) over 180 min. Another 16 swine served as controls. After infusion with LPS or placebo, GLN was administered intravenously, enterally or in combination (0.5 g/kg i.v. plus 0.5 g/kg enterally) over 30 min. At 0, 15, 30, 45, 60, 120 and 180 min, blood was drawn from the systemic and portal circulation for colorimetric assessment of GLN. Results: In healthy, placebo-alone swine, GLN levels remained stable throughout the study. Intravenous and combined infusion increased systemic levels (p = 0.001), but after enteral administration alone, a smaller effect was observed (p = 0.026). Portal levels were increased after combined, enteral and intravenous administration (p = 0.001). In endotoxemia, systemic and portal levels decreased significantly. Intravenous and, to a greater extent, combined administration increased systemic levels (p = 0.001), while enteral administration only had a small effect (p = 0.001). In the portal vein, intravenous and combined treatment increased plasma levels (p = 0.001), whereas enteral supplementation alone had again a small, yet significant effect (p = 0.001). Conclusions: The findings indicate that combined GLN supplementation is superior to intravenous treatment alone, in terms of enhanced availability in systemic and portal circulations. Thus, combined treatment at the onset of endotoxemia is a beneficial practice, ensuring adequate GLN to compensate for the resulting intracellular shortage.

A randomised trial of enteral glutamine supplementation for very preterm children showed no beneficial or adverse long-term neurodevelopmental outcomes.

This study evaluated the long-term effects of enteral glutamine supplementation on neurodevelopmental outcomes of a Dutch cohort of very preterm children at 13years of age. The cohort was enrolled in a randomised placebo-controlled trial between 2001 and 2003 in which infants received glutamine- or alanine-supplemented enteral nutrition during the first month of life. Participants were invited for follow-up at a mean age of 13.30years. Motor, neurocognitive, academic and behavioural outcomes were assessed in 61 children. No differences were found between the groups regarding motor, intellectual, academic and behavioural functioning. Forward span visuospatial working memory performance was better in the controls (crude/adjusted model: d=0.67/0.64, p=0.02/0.02), but no difference was found for backward span. After the data were adjusted for confounders, the groups differed regarding parent-rated attention (crude/adjusted model: d=0.47/0.73, p=0.07/0.003), but both groups scored within the normal range. This was the first study on the long-term effects of enteral glutamine supplementation on the neurodevelopmental outcomes of very preterm children. Our study provided no evidence that enteral glutamine supplementation had any beneficial or adverse effects on the children's motor, neurocognitive, academic and behavioural outcomes at 13years of age.

Influence of enteral glutamine on inflammatory and hormonal response in patients with rectal cancer during preoperative radiochemotherapy.

We conducted a randomized double-blind placebo-controlled study evaluating the influence of 5 weeks' duration of 30 g enteral glutamine supplementation on inflammatory and hormonal responses in 73 patients with rectal cancer undergoing preoperative radiochemotherapy. Plasma levels of inflammatory and hormonal parameters were controlled at the beginning and at the end of supplementation. Enteral glutamine resulted in modulation of inflammatory and hormonal responses as shown by a decreased plasma interleukin 6 and cortisol levels in glutamine compared with placebo group: 5.5±3.8 versus 11.1±19.9 ng/l (P=0.02) for IL-6 and 386±168.4 to 312.7±111.7 nmol/l (P=0.03) for cortisol. We conclude that enteral glutamine exhibits some anti-inflammatory activity and, consequently, leads to a lower hormonal stress response during radiochemotherapy in patients with rectal cancer.

Role of Glutamine Supplementation in Critically ill patients: A Narrative Review

Enteral nutrition has been known to bring about reduction in infectious complications in post major abdominal surgery. Previous systematic reviews and meta-analysis have suggested that immune nutrition in critically ill have been associated with reduced hospital stay, infection rate and inflammatory response. Glutamine is considered an essential amino acid during stress and critical illness. Parenteral glutamine supplementation in critically ill patients has been shown to improve survival rate and minimise infectious complications, costs and hospital length-of-stay. The purpose of this article is to provide a narrativereview of the current evidence and trials of enteral and parenteral glutamine supplementation in multipletrauma patients. A search in PubMed and EMBASE was conducted and relevant papers that investigated the effect of enteral or parenteral glutamine supplementation in patients with multiple trauma were reviewed. Although recent nutritional guidelines recommend that glutamine supplementation should be considered in these patients, further well-designed trials are required to provide a confirmed conclusion. Due to the inconclusive results of enteral glutamine supplementation trials in patients receiving enteral nutrition, future trials should focus on intravenous glutamine supplementation in patients requiring enteral nutrition and on major clinical outcome measures (e.g. mortality rate, infectious complications).

Efficacy of glutamine-enriched enteral feeding formulae in critically ill patients: a systematic review and meta-analysis of randomized controlled trials.

Critically ill patients usually suffer from catabolic stress that could lead to malnutrition and nutritional support therefore is essential to maintain lean body mass, improve metabolic and immune response and decrease rate of mortality and comorbidity in these patients. This meta-analysis was aimed to evaluate effect of glutamineenriched enteral nutrition in critically ill patients. In order to obtain randomized clinical trial studies (RCTs), international databases including MEDLINE and Google scholar and also electronic resources in Iran, including IRAN MEDEX, IRAN DOC, SID, Magiran were systematically searched without language and publication restriction before December 2014. The final included number of studies for meta-analysis was 10. The methodological quality of eligible studies was assessed by four investigators using the Jadad 5-point scale, a scale containing three items describing randomization, blinding and fate of participants. We analyzed data from the included studies using STATA version 12.0, and calculated a pooled odds ratio for dichotomous data and mean differences for continuous data with 95% confidence intervals (CIs). There was no significant difference in mortality in elevated pooled odds ratios (p-value=0.070). A funnel plot was drawn for evaluation of publication bias, but none was found. The fixed effect model shows significant reduction in gut permeability in who received enteral feeding enriched with glutamine (-0.84, 95% CI=-1.25 to -0.44), moreover the funnel plot did not show publication bias. Based on the available data, our meta-analysis showed that enteral glutamine (Gln) supplementation increased mortality rate, though non-significantly, but decreased gut permeability significantly.

Glutamine supplementation to prevent morbidity and mortality in preterm infants.

Glutamine is a conditionally essential amino acid. Endogenous biosynthesis may be insufficient for tissue needs in states of metabolic stress. Evidence exists that glutamine supplementation improves clinical outcomes in critically ill adults. It has been suggested that glutamine supplementation may also benefit preterm infants. To determine the effects of glutamine supplementation on mortality and morbidity in preterm infants. We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, 2015, Issue 12), MEDLINE, EMBASE and Maternity and Infant Care (to December 2015), conference proceedings and previous reviews. Randomised or quasi-randomised controlled trials that compared glutamine supplementation versus no glutamine supplementation in preterm infants at any time from birth to discharge from hospital. We extracted data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by two review authors. We synthesised data using a fixed-effect model and reported typical relative risk, typical risk difference and weighted mean difference. We identified 12 randomised controlled trials in which a total of 2877 preterm infants participated. Six trials assessed enteral glutamine supplementation and six trials assessed parenteral glutamine supplementation. The trials were generally of good methodological quality. Meta-analysis did not find an effect of glutamine supplementation on mortality (typical relative risk 0.97, 95% confidence interval 0.80 to 1.17; risk difference 0.00, 95% confidence interval -0.03 to 0.02) or major neonatal morbidities including the incidence of invasive infection or necrotising enterocolitis. Three trials that assessed neurodevelopmental outcomes in children aged 18 to 24 months and beyond did not find any effects. The available trial data do not provide evidence that glutamine supplementation confers important benefits for preterm infants.

Glutamine supplementation to prevent morbidity and mortality in preterm infants.

Glutamine is a conditionally essential amino acid. Endogenous biosynthesis may be insufficient for tissue needs in states of metabolic stress. Evidence exists that glutamine supplementation improves clinical outcomes in critically ill adults. It has been suggested that glutamine supplementation may also benefit preterm infants. To determine the effects of glutamine supplementation on mortality and morbidity in preterm infants. We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, 2015, Issue 12), MEDLINE, EMBASE and Maternity and Infant Care (to December 2015), conference proceedings and previous reviews. Randomised or quasi-randomised controlled trials that compared glutamine supplementation versus no glutamine supplementation in preterm infants at any time from birth to discharge from hospital. We extracted data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by two review authors. We synthesised data using a fixed-effect model and reported typical relative risk, typical risk difference and weighted mean difference. We identified 12 randomised controlled trials in which a total of 2877 preterm infants participated. Six trials assessed enteral glutamine supplementation and six trials assessed parenteral glutamine supplementation. The trials were generally of good methodological quality. Meta-analysis did not find an effect of glutamine supplementation on mortality (typical relative risk 0.97, 95% confidence interval 0.80 to 1.17; risk difference 0.00, 95% confidence interval -0.03 to 0.02) or major neonatal morbidities including the incidence of invasive infection or necrotising enterocolitis. Three trials that assessed neurodevelopmental outcomes in children aged 18 to 24 months and beyond did not find any effects. The available trial data do not provide evidence that glutamine supplementation confers important benefits for preterm infants.

Immunonutrition - the influence of early postoperative glutamine supplementation in enteral/parenteral nutrition on immune response, wound healing and length of hospital stay in multiple trauma patients and patients after extensive surgery.

Introduction: In the postoperative phase, the prognosis of multiple trauma patients with severe brain injuries as well as of patients with extensive head and neck surgery mainly depends on protein metabolism and the prevention of septic complications. Wound healing problems can also result in markedly longer stays in the intensive care unit and general wards. As a result, the immunostimulation of patients in the postoperative phase is expected to improve their immunological and overall health. Patients and methods: A study involving 15 patients with extensive ENT tumour surgery and 7 multiple-trauma patients investigated the effect of enteral glutamine supplementation on immune induction, wound healing and length of hospital stay. Half of the patients received a glutamine-supplemented diet. The control group received an isocaloric, isonitrogenous diet.Results: In summary, we found that total lymphocyte counts, the percentage of activated CD4+DR+ T helper lymphocytes, the in-vitro response of lymphocytes to mitogens, as well as IL-2 plasma levels normalised faster in patients who received glutamine-supplemented diets than in patients who received isocaloric, isonitrogenous diets and that these parameters were even above normal by the end of the second postoperative week.Summary: We believe that providing critically ill patients with a demand-oriented immunostimulating diet is fully justified as it reduces septic complications, accelerates wound healing, and shortens the length of ICU (intensive care unit) and general ward stays.