Parenteral Glutamine Supplementation Research Articles

Postoperative parenteral glutamine supplementation improves the short-term outcomes in patients undergoing colorectal cancer surgery: A propensity score matching study.

The clinical utility of glutamine in patients undergoing colorectal cancer (CRC) surgery remains unclear. Therefore, we aimed to investigate the impact of postoperative treatment with glutamine on postoperative outcomes in patients undergoing CRC surgery. We included patients with CRC undergoing elective surgery between January 2014 and January 2021. Patients were divided into the glutamine and control groups. We retrospectively analyzed postoperative infections complications within 30 days and other outcomes using propensity score matching and performed between-group comparisons. We included 1,004 patients who underwent CRC surgeries; among them, 660 received parenteral glutamine supplementation. After matching, there were 342 patients in each group. The overall incidence of postoperative complications was 14.9 and 36.8% in the glutamine and control groups, respectively, indicating that glutamine significantly reduced the incidence of postoperative complications [p < 0.001; risk ratio (RR) 0.41 [95% CI 0.30-0.54]]. Compared with the control group, the glutamine group had a significantly lower postoperative infection complications rate (10.5 vs. 28.9%; p < 0.001; RR 0.36 [95% CI 0.26-0.52]). Although there was no significant between-group difference in the time to first fluid diet (p = 0.052), the time to first defecation (p < 0.001), first exhaust (p < 0.001), and first solid diet (p < 0.001), as well as hospital stay (p < 0.001) were significantly shorter in the glutamine group than in the control group. Furthermore, glutamine supplementation significantly reduced the incidence of postoperative intestinal obstruction (p = 0.046). Moreover, glutamine supplementation alleviated the decrease in albumin (p < 0.001), total protein (p < 0.001), and prealbumin levels (p < 0.001). Taken together, postoperative parenteral glutamine supplementation can effectively reduce the incidence of postoperative complications, promote the recovery of intestinal function, and improve albumin levels in patients undergoing CRC surgery.

Effect of Glutamine on Short-term Surgical Outcomes in Rectal Cancer Patients Receiving Neoadjuvant Therapy: A Propensity Score Matching Study

The effect of glutamine on postoperative complications and postoperative recovery in rectal cancer (RC) patients receiving neoadjuvant therapy (NT) is unclear. This study aimed to investigate the effects of intravenous glutamine supplementation on short-term postoperative outcomes in these patients. This retrospective study included patients with RC who received NT and underwent radical surgery between January 2013 and July 2022 and were either administered glutamine (glutamine group) or not administered glutamine (non-glutamine group). Propensity score matching method was used to analyze and compare postoperative complications and other outcome indicators. A total of 208 patients were reviewed, and 53 were included in each group post matching. While no significant difference in the time to first solid food intake between the two groups was observed, the glutamine group had a significantly reduced incidence of postoperative complications, shorter length of hospital stay, and shorter time to first defecation, first exhaust, and first fluid diet intake than those of the control group. Moreover, glutamine alleviated the reduction in albumin and prealbumin levels. Perioperative parenteral glutamine supplementation effectively reduces the incidence of postoperative complications, promotes postoperative recovery, and improves albumin levels in patients undergoing RC surgery and receiving NT.

Effects of Parenteral Glutamine Supplementation on Endocan Levels in Septic Patients

Effects of Parenteral Glutamine Supplementation on Endocan Levels in Septic Patients

Effects of parenteral glutamine in critically ill surgical patients: a systematic review and meta-analysis.

Introduction: glutamine (GLN), the most abundant non-essential amino acid in the plasma, tends to be rapidly depleted in cells in situations of metabolic stress. Some studies have demonstrated the benefits of GLN supplementation on mortality, infection, and length of hospital stay. The objective of this review was to analyze whether parenteral supplementation with GLN has any relevant effect in critically ill surgical patients. Methods: based on a systematic database search, randomized clinical trials (RCTs) published since 1985 were included if they had evaluated the effect of parenteral GLN supplementation in critical surgical patients. The statistical analysis was performed using the RevMan 5.3 software. Results: seven RCTs were eligible for the meta-analysis. Parenteral glutamine supplementation was associated with a non-significant 24 % reduction in mortality (RR = 0.76; 95 % CI: 0.50-1.15). Infections were significantly reduced (RR = 0.60; 95 % CI: 0.45-0.80), and length of hospital stay was 4.09 days shorter (95 % CI: -6.71 to -1.46). Conclusion: parenteral GLN usage in critical surgical patients seems to decrease infection and length of hospital stay, but we could not demonstrate a significant reduction in mortality.

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 parenteral glutamine supplementation in adult hematopoietic stem cell transplantation patients.

BackgroundHematopoietic stem cell transplantation (HSCT) patients need parenteral nutrition because of nausea, vomiting, and mucositis caused by conditioning regimens. The demand for glutamine increases during the HSCT period. We evaluated the effects of glutamine-containing parenteral nutrition on the clinical outcomes of HSCT patients.MethodsIn this retrospective analysis, we reviewed HSCT patients from Seoul National University from August 2013 to July 2017. Depending on their glutamine supplementation status, 91 patients were divided into 2 groups: glutamine group (N=44) and non-glutamine group (N=47). We analyzed the rate of weight change, infection (clinically/microbiologically documented), complications (duration of mucositis and neutropenia, acute graft versus host disease), and 100-days mortality in each group.ResultsRegarding the clinical characteristics of the patients, there were no significant differences between the 2 groups except that there was a larger proportion of myeloablative conditioning regimen in the glutamine group (P=0.005). In the glutamine group, the average number of days of glutamine use, parenteral nutrition, and mucositis was 7.6±1.4, 14.6±9.9, and 13.3±9.5, respectively. Furthermore, multivariate analysis revealed odds ratios of 0.37 (95% CI, 0.14–0.96; P=0.042) and 0.08 (95% CI, 0.01–0.98; P=0.048) for clinically documented infection and 100-days mortality, respectively, in the glutamine group.ConclusionResults showed that the glutamine group had less clinically documented infection and 100-days mortality than the non-glutamine group, but the other outcomes did not show significant differences. The extended duration of glutamine supplementation according to the period of total parenteral nutrition and mucositis should be considered.

Parenteral Glutamine Supplementation, Is It Optimal or Not?

Parenteral Glutamine Supplementation, Is It Optimal or Not?

Effect of parenteral glutamine supplementation combined with enteral nutrition on Hsp90 expression and Peyer's patch apoptosis in severely burned rats.

The aim of this study was to investigate the effects of parenteral glutamine (GLN) supplementation combined with enteral nutrition (EN) on heat shock protein (Hsp) 90 expression and Peyer's patch (PP) apoptosis in severely burned rats. Male Sprague-Dawley (SD) rats were randomly assigned to four groups: Sham burn+EN+GLN-free amino acid (AA; n=10), sham burn+EN+GLN (n=10), burn+EN+AA (n=10), and burn+EN+GLN (n=10). Two hours after a 30% total body surface area (TBSA), full-thickness scald burn injury on the back, burned rats in two of the experimental groups (burn+EN+AA and burn+EN+GLN groups) were fed with a conventional EN solution by oral gavage for 7d. Simultaneously, rats in the burn+EN+GLN group were given 0.35g GLN/kg body weight/d once via a tail vein injection for 7d and rats in the burn+EN+AA group were administered isocaloric/isonitrogenous GLN-free amino acid solution (Tyrosine) for comparison. Rats in two sham burn control groups (sham burn+EN+AA and sham burn+EN+GLN groups) were treated in the same manner except for the burn injury. All rats in the four groups were given 175kcal/kg body wt/d. There was isonitrogenous, isovolumic, and isocaloric intake among the four groups. At the end of the seventh day after completion of the nutritional program, all rats were anesthetized and samples were collected for further analysis. PP apoptosis was measured by terminal deoxyuridine nick-end labeling (TUNEL). The expression of Hsp90 in PPs was analyzed by western blotting. Caspase-3 activity of PPs was also assessed. Levels of proinflammatory cytokines of gut tissues were evaluated by enzyme-linked immunosorbent assay (ELISA). The intestinal immunoglobulin A (IgA) content was also determined by ELISA. The results revealed that intestinal IgA content in rats of the burn+EN+GLN group were significantly increased compared with those in the burn+EN+AA group (P<0.05). The expression of Hsp90 of PPs in rats in the burn+EN+GLN group was significantly upregulated compared with those in the burn+EN+AA group (P<0.05). On the other hand, levels of proinflammatory cytokines of gut tissues, caspase-3 activity, and the number of TUNEL-stained cells of PPs in rats of the burn+EN+GLN group were markedly decreased compared with those of the burn+EN+AA group (P<0.05). The results of this study show that parenteral glutamine supplementation combined with EN may upregulate the expression of Hsp90, reduce caspase-3 activity, lessen the release of proinflammatory cytokines, attenuate PP apoptosis, and improve intestinal IgA response in burned rats. Clinically, therapeutic efforts to improve intestinal immunity may contribute to a favorable outcome in severely burned patients.

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.

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).

Effect of parenteral glutamine supplementation combined with enteral nutrition on Hsp90 expression and lymphoid organ apoptosis in severely burned rats

ObjectiveThe aim of this study is to investigate the effects of parenteral glutamine(GLN) supplementation combined with enteral nutrition (EN) on heat shock protein 90(Hsp90) expression, apoptosis of lymphoid organs and circulating lymphocytes, immunological function and survival in severely burned rats. MethodsMale SD rats were randomly assigned into 4 groups: a sham burn+EN+GLN-free amino acid (AA) group (n=10), a sham burn+EN+GLN group (n=10), a burn+EN+AA group (n=10), and a burn +EN +GLN group (n=10). Two hours after a 30% total body surface area (TBSA), full-thickness scald burn injury on the back was made, the burned rats in two experimental groups (the burn+EN+AA group and the burn+EN +GLN group) were fed with a conventional enteral nutrition solution by oral gavage for 7 days. Simultaneously, the rats in the burn+EN+GLN group were given 0.35g GLN/kg body weight/day once via a tail vein injection for 7 days, whereas those in the burn+EN+AA group were administered isocaloric/isonitrogenous GLN-free amino acid solution (Tyrosine) for comparison. The rats in two sham burn control groups (the sham burn+EN+AA group and the sham burn+EN +GLN group) were treated in the same procedure as above, except for burn injury. All rats in each of the four groups were given 175kcal/kg body wt/day. There was isonitrogenous, isovolumic and isocaloric intake among four groups. At the end of the 7th day after nutritional programme were finished, all rats were anesthetized and samples were collected for further analysis. Serum immunoglobulin quantification was conducted by ELISA. Circulating lymphocyte numbers were counted by Coulter LH-750 Analyzer. The percentages and apoptotic ratio of CD4 and CD8T lymphocytes in circulation were determined by flow cytometry (FCM). The neutrophil phagocytosis index (NPI) was examined. The GLN concentrations in plasma, thymus, spleen and skeletal muscle were measured by high performance liquid chromatography (HPLC). The organ index evaluation and TUNEL analysis of thymus and spleen were carried out. The expression of Hsp90 in thymus and spleen was analyzed by western blotting. Moreover, the survival in burned rats was observed. ResultsThe results revealed that parenteral GLN supplementation combined with EN significantly increased the GLN concentrations of plasma and tissues, the serum immunoglobulin content, the circulating lymphocyte number, the CD4/CD8 ratio, the indexes of thymus and spleen, NPI and survival as compared with the burn+EN+AA group (p<0.05). The expression of Hsp90 in thymus and spleen in the burn+EN+GLN group was significantly up-regulated as compared with the burn+EN+AA group (p<0.05). The apoptosis in circulating CD4 and CD8 lymphocytes, thymus and spleen in the burn+EN+GLN group was significantly decreased as compared with the burn+EN+AA group (p<0.05). ConclusionThe results of this study show that parenteral GLN supplementation combined with EN may increase the GLN concentrations of plasma and tissues, up-regulate the expression of Hsp90, attenuate apoptosis in lymphoid organ and circulating lymphocyte, enhance the immunological function and improve survival in severely burned rats. Clinically, therapeutic efforts at the modulation of the immune dysfunction may contribute to a favorable outcome in severely burned patients.

Perioperative glutamine supplementation restores disturbed renal arginine synthesis after open aortic surgery: a randomized controlled clinical trial.

Postoperative renal failure is a common complication after open repair of an abdominal aortic aneurysm. The amino acid arginine is formed in the kidneys from its precursor citrulline, and citrulline is formed from glutamine in the intestines. Arginine enhances the function of the immune and cardiovascular systems, which is important for recovery after surgery. We hypothesized that renal arginine production is diminished after ischemia-reperfusion injury caused by clamping of the aorta during open abdominal aortic surgery and that parenteral glutamine supplementation might compensate for this impaired arginine synthesis. This open-label clinical trial randomized patients who underwent clamping of the aorta during open abdominal aortic surgery to receive a perioperative supplement of intravenous alanyl-glutamine (0.5 g·kg(-1)·day(-1); group A, n = 5) or no supplement (group B, n = 5). One day after surgery, stable isotopes and tracer methods were used to analyze the metabolism and conversion of glutamine, citrulline, and arginine. Whole body plasma flux of glutamine, citrulline, and arginine was significantly higher in group A than in group B (glutamine: 391 ± 34 vs. 258 ± 19 μmol·kg(-1)·h(-1), citrulline: 5.7 ± 0.4 vs. 2.8 ± 0.4 μmol·kg(-1)·h(-1), and arginine: 50 ± 4 vs. 26 ± 2 μmol·kg(-1)·h(-1), P < 0.01), as was the synthesis of citrulline from glutamine (4.8 ± 0.7 vs. 1.6 ± 0.3 μmol·kg(-1)·h(-1)), citrulline from arginine (2.3 ± 0.3 vs. 0.96 ± 0.1 μmol·kg(-1)·h(-1)), and arginine from glutamine (7.7 ± 0.4 vs. 2.8 ± 0.2 μmol·kg(-1)·h(-1)), respectively (P < 0.001 for all). In conclusion, the production of citrulline and arginine is severely reduced after clamping during aortic surgery. This study shows that an intravenous supplement of glutamine increases the production of citrulline and arginine and compensates for the inhibitory effect of ischemia-reperfusion injury.

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.

Effect of Previous High Glutamine Infusion on Inflammatory Mediators and Mortality in an Acute Pancreatitis Model.

Parenteral glutamine supplementation in acute inflammatory conditions is controversial. We evaluated the inflammatory and survival responses after parenteral glutamine infusion in sodium taurocholate-induced acute pancreatitis (AP) model. Lewis rats received 1 g/kg parenteral glutamine (n = 42), saline (n = 44), or no treatment (n = 45) for 48 h before AP induction. Blood, lung, and liver samples were collected 2, 12, and 24 h after AP to measure serum cytokines levels and tissue heat shock protein (HSP) expression. From each group, 20 animals were not sacrificed after AP for a 7-day mortality study. Serum cytokine levels did not differ among groups at any time point, but the intragroup analysis over time showed higher interferon-γ only in the nontreatment and saline groups at 2 h (versus 12 and 24 h; both p ≤ 0.05). The glutamine group exhibited greater lung and liver HSP90 expression than did the nontreatment group at 2 and 12 h, respectively; greater liver HSP90 and HSP70 expression than did the saline group at 12 h; and smaller lung HSP70 and liver HSP90 expression than did the nontreatment group at 24 h (all p ≤ 0.019). The 7-day mortality rate did not differ among groups. In experimental AP, pretreatment with parenteral glutamine was safe and improved early inflammatory mediator profiles without affecting mortality.

Role of Parenteral Glutamine in Nutrition Support for Critically Ill Patients

Glutamine is the most abundant amino acid, composed of more than 50 percent of free amino acid in the human body. It had been regarded as a conditional essential amino acid and its concentration is markedly reduced in critically ill patients with trauma, burn, or sepsis. From the early 1990s, many parenteral glutamine studies on critical illness have reported the benefits in mortality, infection, and length of stay. However, its clinical efficacy was based on out-of-date, smaller, single-center studies. Clinical effects of parenteral glutamine have shown no benefits or even harms in recent clinical trials and meta-analysis. Furthermore, it has challenged the hypothesis that low plasma glutamine concentration was associated with poor outcomes in critically ill patients. Although many studies showing the efficacy of glutamine have been reported, parenteral glutamine supplementation may be harmful in patients with multiorgan failure or baseline kidney dysfunction. Further studies should be conducted to identify the use of glutamine supplementation in combination with parenteral and enteral nutrition or enteral/oral nutrition alone, specific adult or pediatric patients, the appropriate time and doses for administration of glutamine, cost-benefit analysis, and the exact mechanisms of action.

Effects of enteral nutrition with parenteral glutamine supplementation on the immunological function in septic rats.

The aim of the present study was to investigate the effects of enteral nutrition (EN) with parenteral glutamine (GLN) supplementation on inflammatory response, lymphatic organ apoptosis, immunological function and survival in septic rats by caecal ligation and puncture (CLP). Male rats were randomly assigned into two experimental groups and two sham CLP control groups (n 10 per group). After CLP or sham CLP model and nutrition programme were completed, the GLN concentrations of plasma and tissues and several indices of immunological function including serum Ig content, circulating lymphocyte number, the CD4:CD8 ratio, the neutrophil phagocytosis index (NPI), the organ index and apoptosis of thymus and spleen, and plasma cytokine levels were determined. Moreover, the survival in septic rats was observed. The results revealed that EN with parenteral GLN supplementation remarkably increased the GLN concentrations of plasma and tissues, serum Ig content, the circulating lymphocyte number, the CD4:CD8 ratio, the indexes of thymus and spleen, NPI and survival compared with the control group (P< 0·05). In contrast, the apoptosis of thymus and spleen and the levels of TNF-α, IL-1β and IL-6 in plasma were obviously decreased compared with the control group (P< 0·05). These results show that EN with parenteral GLN supplementation diminished the release of inflammatory cytokines, attenuated lymphatic organ apoptosis, enhanced the immunological function and improved survival in septic rats.

Parenteral glutamine supplementation in combination with enteral nutrition improves intestinal immunity in septic rats

ObjectivesThe gut-associated lymphoid tissue is continuously exposed to antigens in the gut lumen and becomes the first line of defense against enteric bacteria and associated toxin. The aim of this study was to investigate the effects of parenteral glutamine (GLN) supplementation in combination with enteral nutrition (EN) on intestinal mucosal immunity in septic rats by cecal ligation and puncture (CLP). MethodsMale Sprague-Dawley rats were randomly assigned into four groups: A sham CLP + EN + saline group (n = 10), a sham CLP + EN + GLN group (n = 10), a CLP + EN + saline group (n = 10), and a CLP + EN + GLN group (n = 10). At 2 h after CLP or sham CLP, all rats in each of the four groups received an identical enteral nutrition solution as their base formula. Then, the rats in the sham CLP + EN + GLN group and CLP + EN + GLN group were given 0.35 g GLN/kg body weight daily for 7 d, all at the same time, via a tail vein injection; whereas those in the sham CLP + EN + saline group and CLP + EN + saline group were daily administered isovolumic sterile 0.9% saline for comparison. All rats in each of the four groups were given 290 kcal/kg body wt/d for 7 d. At the end of the seventh day after the nutritional program was finished, all rats were euthanized and the entire intestine was collected. Total Peyer's patches (PP) cell yield was counted by a hemocytometer. The percentage of PP lymphocyte subsets was analyzed by flow cytometry. The number of intestinal lamina propria IgA plasma cells was determined by the immunohistochemistry technique. The intestinal immunoglobulin A (IgA) levels were assessed by ELISA. PP apoptosis was evaluated by terminal deoxyuridine nick-end labeling. ResultsThe results revealed total PP cell yield, the numbers of PP lymphocyte subsets, intestinal lamina propria IgA plasma cells, and intestinal IgA levels in the CLP + EN + GLN group were significantly increased when compared with the CLP + EN + saline group (P < 0.05). On the other hand, the number of TUNEL-stained cells within PPs in the CLP + EN + GLN group was markedly decreased as compared with the CLP + EN + saline group (P < 0.05). ConclusionThe results of this study show that parenteral glutamine supplementation in combination with enteral nutrition may attenuate PP apoptosis, increase PP cell yield and intestinal lamina propria IgA plasma cells, and subsequently improve intestinal mucosal immunity. Clinically, these results suggest therapeutic efforts at improving intestinal immunity may contribute to the prevention and treatment of sepsis.

Intravenous glutamine supplementation enhances renal de novo arginine synthesis in humans: a stable isotope study

Arginine plays a role in many different pathways in multiple cell types. Consequently, a shortage of arginine, caused by pathologic conditions such as cancer or injury, has the potential to disturb many cellular and organ functions. Glutamine is the ultimate source for de novo synthesis of arginine in humans via the intestinal-renal axis. Therefore, we hypothesized that parenteral glutamine supplementation may stimulate the interorgan pathway of arginine production. The objectives were to quantify arginine production from its precursor glutamine and to establish the contribution of the kidneys to de novo synthesis of arginine in patients receiving intravenous supplementation of glutamine dipeptide during major abdominal surgery. Whole-body and renal metabolism of glutamine, citrulline, and arginine was assessed by stable isotope techniques in 7 patients receiving a perioperative supplement of intravenous alanyl-glutamine (0.5 g · kg(-1) · d(-1)). Plasma glutamine, citrulline, and arginine concentrations increased significantly in patients receiving intravenous glutamine dipeptide. At whole-body level, 91% of total citrulline turnover was derived from glutamine, whereas 49% of whole-body citrulline turnover was used for de novo synthesis of arginine. The kidneys were responsible for 75% of whole-body arginine production from citrulline. Glutamine and citrulline are important sources for de novo arginine synthesis. The kidneys are the main production site for endogenous arginine. After comparison of these results with previous similar studies, our data suggest that an intravenous glutamine supplement doubles renal arginine production from citrulline. This trial was registered at www.trialregister.nl as NTR2914.

Uncertainty about the safety of supplemental glutamine: an editorial on "A randomized trial of glutamine and antioxidants in critically ill patients".

Previously small randomized clinical trials and several meta-analyses have suggested improved patient outcomes from parenteral glutamine supplementation. A recent large multi-center randomized trial conducted in critically ill patients with documented multiple organ failure at enrollment demonstrated an increase in mortality among those receiving supplemental glutamine. This article discusses the discrepancies in trial outcomes and the risks associated with glutamine administration during critical illness.