Glutamine-enriched Total Parenteral Nutrition Research Articles

Is additional enrichment of diet in branched-chain amino acids or glutamine beneficial for patients receiving total parenteral nutrition after gastrointestinal cancer surgery?

Total Parenteral Nutrition (TPN) is necessary in patients unable to receive oral or enteral feeding for a period of at least 7 days. Branched-chain amino acids (BCAA): valine (Val), leucine (Leu), and isoleucine (Ile) are essential amino acids, which are important regulators in protein metabolism. They are also the main nitrogen source for glutamine synthesis in muscles. In this process they undergo irreversible degradation and cannot be reutilised for protein synthesis. In catabolic states, like cancers, glutamine demand increases and therefore also its utilisation, which can decrease the level of BCAA required for Gln synthesis. The purpose of this study was to evaluate the necessity of BCAA or glutamine-enriched TPN in patients after gastrointestinal cancers surgery. Our aim was to investigate changes of plasma BCAA and glutamine concentrations in patients operated for colorectal, small intestine or pancreatic cancer and who are either receiving TPN or not in the postoperative period. Free amino acids plasma concentrations were determined by the ion-exchange chromatography. Surgery in the control group caused a decrease in Val, Ile and Leu concentrations in the postoperative period. In TPN patients this depression was inhibited beginning from the third day after surgery, except for Val and Leu in colorectal cancer group. In control and TPN patient groups, Gln concentration decreased after the surgery and subsequently increased beginning from the third day after the operation. Gastrointestinal cancer patients' surgery results in decrease in BCAA concentrations. Standard TPN exerts a beneficial effect on the BCAA level in patients with pancreatic and small intestine cancer. In colorectal cancer such TPN should be enriched with Leu and Val.

The Inflammatory Modulation Effect of Glutamine-Enriched Total Parenteral Nutrition in Postoperative Gastrointestinal Cancer Patients

The objective of this study is to explore the inflammatory modulation effect of glutamine-enriched total parenteral nutrition (TPN) by investigating the alterations of inflammation-related cytokines in gastrointestinal (GI) cancer patients postoperatively. Fifty GI cancer patients received postoperative 7 days of isocaloric and isonitrogenous TPN after operation. They were randomly divided to receive either glutamine-enriched TPN or standard TPN. The inflammation-related cytokines including interleukin-6, interleukin-10, and tumor necrosis factor-α were also determined. Records of nutritional assessments, inflammatory status, and postoperative complications were compared between the two groups. Of 50 enrolled patients, 25 patients were classified as the intervention group, and the control group also comprised 25 patients. The differences of gender, age, primary GI malignancies, and hematological and biochemical data between the two compared groups were not statistically significant (all P > 0.05). Compared with standard TPN, a higher serum prealbumin level and better nitrogen balance were observed in glutamine-enriched TPN (P = 0.039 and 0.048 respectively). A significantly lower serum interleukin-6 level was found in comparing glutamine-enriched with standard TPN (P = 0.01), but not in interleukin-10 (P = 0.374) and tumor necrosis factor-α levels (P = 0.653). Moreover, a significant lower serum C-reactive protein level was detected in glutamine-enriched TPN compared with standard TPN (P = 0.013). Indeed, four cases of postoperative infectious complications were noted in the control group, but no postoperative infectious complications were observed in the interventional group (P = 0.037). Our present study shows that glutamine-enriched TPN may be beneficial in improving the inflammatory status and decreasing the infectious morbidity in postoperative GI cancer patients.

Glutamine-supplemented total parenteral nutrition improves immunological status in anorectic patients

Objective Glutamine is an important substrate for critical cells of the immune system, in particular lymphocytes and macrophages, and it is considered a conditionally essential amino acid. Several studies have indicated that glutamine-enriched total parenteral nutrition improves immunologic status and shortens length of stay of critically ill patients. We investigated the effect of total parenteral nutrition supplemented with glutamine on the immune system in anorectic patients. Methods Thirty-six anorectic patients were randomized to receive standard parenteral nutrition or parenteral nutrition supplemented with glutamine 0.18 g · kg −1 · d −1 for 20 d. To evaluate the immune system status, we determined serum levels of neopterin and insulin growth factor-1 and lymphocyte count at baseline and after 10 and 20 d from the beginning of the therapy. Results and Conclusions The results showed a significant increase of the serum levels of neopterin after 10 d of treatment with glutamine (26.44 ± 3.08 versus 6.75 ± 1.73 nmol/L, P < 0.001), thus proving a probable stimulating action carried out by glutamine on the immune system, as testified by the increase of lymphocytes.

Effects of glutamine-enriched total parenteral nutrition on acute pancreatitis

This study was performed to determine the effects of glutamine enriched total parenteral nutrition (TPN) on the patients with acute pancreatitis (AP). Forty patients with AP, who had Ranson's score between 2 and 4 received either standard TPN (control group) or TPN with glutamine (treatment group). The patients in the treatment group received TPN containing 0.3 g/kg/days glutamine. At the end of the study, patients were evaluated for nutritional and inflammatory parameters, length of TPN and length of hospital stay. The length of TPN applications were 10.5+/-3.6 days and 11.6+/-2.5 days, and the length of hospital stays were 14.2+/-4.4 and 16.4+/-3.9 days for the treatment and control groups (NS), and the complication rates in the treatment and control groups were 10 and 40%, respectively (P<0.05). The transferrin level increased by 11.7% in the group that received glutamine-enriched TPN (P<0.05), whereas the transferrin level decreased by 12.1% in the control group (NS). At the end of the study, slight but not significant changes were determined in both groups in fasting blood sugar, albumin, blood urea nitrogen (BUN), creatinine, total cholesterol concentrations, aspartate aminotransferase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH) activities, leukocytes, CD(4), CD(8), serum Zn, Ca and P levels compare to the baseline levels (NS). Significant decreases were determined in serum lipase, amylase activities and C-reactive protein (CRP) levels in both groups (P<0.05). The results of this study have shown that glutamine supplementation to TPN have beneficial effects on the prevention of complications in patients with AP.

Glutamine-enriched total parenteral nutrition in patients with inflammatory bowel disease

Studies in animal models of inflammatory bowel disease (IBD) suggest that supplementation of total parenteral nutrition with glutamine (gln), a conditionally essential amino acid in catabolic conditions, increases gln plasma concentrations, reduces intestinal damage, improves nitrogen balance and may improve the course of the disease. However, human data supporting this assumption are missing. A total of 24 consecutive patients with an acute exacerbation of IBD (19 Crohn's disease; five ulcerative colitis) and scheduled for total parenteral nutrition (TPN) (>7 days) were randomised. Parallel to a standardised anti-inflammatory therapy, the patients received either a TPN with 1.5 g/kg body weight of a standard amino acid or an isonitrogenic, isocaloric TPN with 1.2 g/kg body weight of a standard amino acid and 0.3 g/kg L-alanine-L-glutamine. Primary end points were gln plasma concentrations and intestinal permeability assessed by urinary lactulose and D-xylose ratio. Gln plasma levels did not differ significantly in either group throughout the study. Intestinal permeability did not change within 7 days either with or without gln supplementation (Delta-lactulose/xylose ratio: 0.01+/-0.05 (gln+) vs 0.02+/-0.1 (gln-)). The observed changes in inflammatory and nutritional parameters, and also disease activity, length of TPN and hospital stay, were independent of glutamine substitution. Five (41%) patients in the gln+ group and three (25%) patients in the gln- group needed surgical intervention. Although limited by the sample size, these results do not support the hypothesis that glutamine substitution has an obvious biochemical or clinical benefit in patients with active IBD scheduled for total parenteral nutrition.

Does glutamine-enriched parenteral nutrition really affect intestinal morphology and gut permeability?

Background: Nutritional depletion has been related to low glutamine levels in plasma and gut mucosa. This study was set up to investigate the effects of glutamine-enriched total parenteral nutrition on intestinal morphology and permeability. Methods: Twenty-three depleted patients were randomized and after stabilization baseline measurements were performed. Plasma glutamine concentrations, gut morphology (including proliferation and lymphocyte markers) and intestinal permeability were measured. After administration during 8–10 days of a glutamine enriched total parenteral nutrition or an isonitrogenous control solution the measurements were repeated. Results: No significant changes in glutamine concentrations, intestinal permeability, mucosal morphology or gut mucosal inflammation were observed between groups. Conclusions: Glutamine enriched total parenteral nutrition in a depleted patient population does not result in improvements in gut morphology and gut barrier function.

Effect of glutamine dipeptide on hepatic regeneration in partially hepatectomized malnourished rats

Objective Glutamine promotes hepatic regeneration in nourished (N) rats. The aim of the present study was to evaluate the effects of glutamine-enriched total parenteral nutrition (TPN) on liver regeneration in malnourished (MN) rats. Methods Seventy-two male Wistar rats (≅270 g) were assigned to one of two groups: N and MN. Each group was then subdivided into three groups: the first underwent partial hepatectomy (PH) and received standard TPN enriched with l-alanyl- l-glutamine (Ala-Gln); the second also underwent PH and received standard TPN, but enriched with a solution containing proline and alanine (Ala-Pro); and the third underwent no surgical procedure (control group). All experimental groups received isocaloric (188 kcal · kg −1 · d −1) and isonitrogenous (1.12 g of nitrogen · kg −1 · d −1) TPN for 96 h. All animals were injected with bromodeoxyuridine 2 h before death. The hepatic regeneration index (HRI), hepatic growth percentage (HG) and hepatic morphology were analyzed. Results In MN rats, HRI and HG were higher with glutamine enrichment (HRI = 81 and HG = 190) than with proline-containing TPN (HRI = 66 and HG = 154; P < 0.05) and HRI was 100 times higher in animals that underwent PH than in control animals. Morphologic analysis of hepatic tissue showed no difference among the six groups. Conclusion Glutamine-enriched TPN promoted growth of the remnant liver in MN rats after PH, maintained cellular proliferation in the various experimental groups after surgery, and maintained hepatic morphology of MN rats after surgery.

Immunonutrients and the Critically Ill Neonate

After completing this article, readers should be able to: 1. List the otherwise “nonessential” nutrients that may be required by the critically ill neonate. 2. Explain why omega-3 fatty acids do not cause as much inflammation as their omega-6 counterparts. 3. Define pre- and probiotics and describe how they can prevent colonization of the intestine by pathogenic organisms. 4. Describe the potential protective effects of lactoferrin on the neonatal gastrointestinal tract. In a critically ill individual, the intestinal barrier becomes compromised because of stress, lack of enteral feedings, and ischemic-reperfusion injury. In the preterm neonate, the mucosal barrier is not fully functional (see article on innate immunity in this issue of NeoReviews ). The combination of a damaged and immature gut barrier may lead to increased intestinal permeability, aberrant antigen transfer, and immune response, which can explain the vulnerability to infection, inflammation, and hypersensitivity at an early age. In patients dying of sepsis, there is clear evidence of an imbalance in pro- and anti-inflammatory cytokine production, a failure to maintain antioxidant defenses, and high levels of activation of nuclear factor- kappa-B (NF-kappa-B). Over the past several years, it has become more evident that the proinflammatory cytokine response, as part of an uncontrolled systemic inflammatory response syndrome (SIRS), plays an integral role in premature labor, chronic lung disease, cerebral palsy, necrotizing enterocolitis (NEC), and sepsis. Because the gut is a primary origin of SIRS, it is reasonable to suggest that nutritional agents might stabilize the intestinal mocosal barrier, alter the balance of pro- and anti- inflammatory cytokines, and prevent excessive activation of NF-kappa-B or other signaling pathways. Some nutrients, such as glutamine, arginine, omega-3 fatty acids, nucleotides, and probiotics, have been shown to have a considerable influence on immune function (eg, delayed hypersensitivity, lymphocyte subpopulation counts, immunologic test) and improve metabolic and nutritional indices such as …

Effect of glutamine-enriched total parenteral nutrition in patients with acute pancreatitis

Background: The management of acute pancreatitis (AP) frequently includes parenteral nutrition, but conditionally essential amino acids such as glutamine are not included in conventional total parenteral nutrition (TPN). Aim: This study was conducted to determine whether the inclusion of glutamine has a beneficial effect in patients with AP receiving TPN. Methods: In a randomized, controlled study 28 patients with AP received either a standard TPN with 1.5 g/kg body weight protein or an isonitrogen, isocaloric TPN which contains 0.3 g/kg L -alanine- L -glutamine. Patients were assessed for nutritional and inflammatory parameters, infectious complications, length of TPN, length of hospital stay (LOS) and cost of TPN. Results: There were no side-effects related to glutamine substitution observed. Glutamine was associated with a significant increase of cholinesterase, albumin and lymphocyte count in AP as well a decrease of C-reactive protein compared to standard TPN at day 14. There was a reduced length of TPN (10 [6–16] vs 16 [10–18] days, P<0.05) and a trend of reduced LOS (21 [14–32] vs 25 [19–40] days) in AP patients receiving glutamine. The overall cost per patient for TPN did not differ (gln+: 929±586 vs gln−: 981±507 euro/patient). Conclusion: Our results suggest that glutamine substitution is beneficial and does not increase the overall cost of parenteral feeding in patients with acute pancreatitis.

Combination of recombinant human growth hormone and glutamine-enriched total parenteral nutrition to surgical patients: effects on circulating amino acids

Background & Aims: Both recombinant human growth hormone (rhGH) and glutamine (GLN) may have beneficial anabolic actions on amino acid metabolism. The aim of this study was to evaluate the additive effects of rhGH and GLN on plasma amino acids postoperatively.Methods: 31 females undergoing laparoscopic cholecystectomy were randomized to three groups: Group I (n=10) received 13 IU/m2 of rhGH the morning of surgery and the following three postoperative days, together with glutamine-free TPN for the first two postoperative days. Group II (n=11) received rhGH as the first group, together with glutamine-enriched (7 g GLN/m2/day) TPN. Group III (n=10) received glutamine-enriched TPN as the second group, but rhGH was replaced by placebo. Daily plasma amino acid concentrations and nitrogen balance were determined.Results: In the GH treated groups, the plasma concentrations of several amino acids were decreased on the third postoperative day, compared to preoperatively. This was not observed in Group III. The changes were more pronounced in Group II. In Group II the negative AV-differences of amino acids tended to be attenuated, while the patients in Group III had increased negative AV-differences. The cumulative nitrogen balance was significantly improved in the GH groups, compared with Group III.Conclusion: The combined treatment of growth hormone and glutamine has additive effects on AV-balances of amino acids postoperatively, whereas nitrogen balance is not further improved when adding glutamine to rhGH treatment.

Tissue antioxidant capacity and bacterial translocation under total parenteral nutrition.

Alterations in the antioxidative system have been observed during total parenteral nutrition (TPN). Light exposure or changes in the composition of TPN formulas may affect this system. Bacterial translocation (BT) is frequent under TPN and may be related to oxidative status. The aim of this study was to determine the adverse effects of standard and glutamine-enriched TPN, with or without light exposure, on oxidative status (liver and kidney-reduced glutathione, GSH) and its relationship to BT. Thirty-three adult Wistar rats underwent central-venous cannulation and were randomly assigned to one of four groups receiving different TPN regimes for 10 days. The TPN group (n = 10) had standard TPN, the TPN(-) group (n = 8) standard TPN without light exposure, the GTPN group (n = 8) glutamine-enriched TPN, and the GTPN(-) group (n = 7) glutamine-enriched TPN without light exposure. A sham group (n = 16) receiving chow and water ad libitum and saline i.v. served as controls. At the end of the experiment, GSH was determined in liver and kidney tissue. Mesenteric lymph nodes and peripheral and portal blood samples were cultured for BT. Compared to sham rats, TPN groups had statistically significant lower GSH levels, but there were no differences between standard or glutamine-enriched groups or light-exposure groups. Sham animals had 12% BT. Significantly higher BT (P < 0.05) occurred in TPN rats: 70% in the TPN group, 88% in the TPN(-) group, 86% in GTPN (-) animals, and only 50% in the GTPN group (P = 0.06 vs TPN group). In conclusion, (1) TPN reduces antioxidant capacity; (2) glutamine supplementation or light protection does not improve tissue antioxidant capacity under TPN; (3) the absence of light exposure does not improve TPN-related BT; and (4) glutamine supplementation tends to reduce BT only in the presence of light.

Enteral glutamine feeding and some aspects of immune function in intensive care patients

Glutamine-enriched total parenteral nutrition (TPN) is beneficial in reducing both infective complications and mortality of critically ill patients. Similar results were observed in bone marrow transplant patients, as well as increased circulating numbers of lymphocytes, in particular T-cell subsets. An increase was observed in T-cell DNA synthesis in colorectal cancer patients receiving glutamine-enriched TPN. However, TPN is associated with complications such as intestinal atrophy, and enteral nutrition is now the preferred route. The present study assessed the effects of feeding glutamine enterally in 14 intensive care patients who were not immunosuppressed. Blood samples were analysed for plasma glutamine concentration (enzymatically), lymphocyte proliferation via 3H thymidine incorporation into DNA (counts per minute — CPM) with and without mitogenic stimulation (Concanavalin-A), neutrophil activity (using an oxidative burst technique) and cytokine production in culture medium (IL-2 and IL-8). Patients were randomly divided into two groups and fed 15-g bolus doses in water of either glutamine (n = 7; 60 ± 8 years) or placebo (n = 7; 60 ± 6 years) for 5 days. Nasogastric nutrition was discontinued daily at midday and a blood sample was taken; 1 hour later, a bolus dose of glutamine/placebo was administered via the tube; 2 hours later total nutrition was started again. Lymphocyte proliferation increased in the glutamine group (P < 0.04) compared with the placebo, as measured by CPM and the stimulation index. IL-2 production increased in culture medium from Day 0 to Day 5 for patients receiving glutamine (P < 0.02) compared with the placebo group. IL-8 production, neutrophil numbers or activity, and plasma glutamine did not change. Our results suggest that glutamine is able to induce an IL-2 mediated increase in the proliferative ability of T-cells, and we hypothesise that these changes may underlie previously observed clinical benefits from glutamine administration in critically ill patients.

Response of glutamine metabolism to glutamine-supplemented parenteral nutrition

Increasing evidence suggests that glutamine is important for the function of many organ systems and supports the use of glutamine-enriched total parenteral nutrition (TPN) during severe illness. However, the effect of prolonged glutamine supplementation on glutamine kinetics has not been studied. We investigated the effect of 8-10 d of TPN enriched with glutamine dipeptides on glutamine kinetics. Twenty-three preoperative patients were randomly allocated to receive either TPN enriched with glutamine dipeptides (60 micromol glutamine*kg body wt(-1)*h(-1)) or isonitrogenous, isoenergetic, glutamine-free TPN. A primed, continuous, 6-h intravenous infusion of L-[5-(15)N]glutamine and L-[1-(13)C]leucine was given before (baseline) and 8-10 d after the TPN solutions were administered. Baseline measurements were performed after a 40-h administration of a standard solution of glucose and amino acids (no glutamine). Glutamine-enriched TPN increased the total appearance rate of glutamine (P: < 0.05) but did not inhibit or increase the endogenous appearance rate. The standard TPN solution also increased the glutamine appearance rate (P: < 0.05), but the change was much smaller than in the glutamine-supplemented group (P: < 0.01). The plasma glutamine concentration did not rise significantly during either treatment, suggesting increased tissue glutamine utilization, especially in the glutamine-supplemented group. In view of the enhanced glutamine requirements in response to trauma and disease by tissues such as those of the gut, the immune system, and the liver, increased glutamine availability during glutamine-enriched TPN may be beneficial preoperatively in patients with gastrointestinal disease.

Glutamine-enriched total parenteral nutrition maintains intestinal interleukin-4 and mucosal immunoglobulin A levels.

Total parenteral nutrition (TPN) prevents progressive malnutrition but fails to maintain intestinal gut-associated lymphoid tissue (GALT) or established respiratory antiviral or antibacterial mucosal immunity. Our previous work demonstrated that decreases in intestinal immunoglobulin A (IgA) were associated with decreases in Th2-type IgA-stimulating cytokines, interleukin (IL)-4 and IL-10. Because glutamine supplementation of TPN partially preserves respiratory defenses and normalizes GALT, we investigated the ability of parenteral glutamine to normalize respiratory and intestinal IgA levels and measured Th2 cytokines in intestinal homogenates. Animals were cannulated and randomly assigned to receive chow (n = 17), TPN (n = 18), or an isonitrogenous, isocaloric TPN solution formulated by removing the appropriate amount of amino acids and replacing them with 2% glutamine (n = 18) for 5 days. Respiratory tract and intestinal washings were obtained for IgA and the intestine homogenized and analyzed for IL-4 and IL-10. TPN decreased intestinal and respiratory IgA in association with decreases in intestinal IL-4 and IL-10 compared with chow-fed animals. Glutamine significantly improved respiratory and intestinal IgA levels, significantly improved IL-4 compared with TPN animals, and maintained IL-10 levels midway between chow-fed and TPN animals. Glutamine-enriched TPN preserved both extraintestinal and intestinal IgA levels and had a normalizing effect on Th2-type IgA-stimulating cytokines.

Effects of parenteral nutrition supplemented with glutamine or glutamine dipeptides on liver antioxidant and detoxication systems in rats

Our aim was to determine the effects of glutamine or alanyl glutamine parenteral supplementation on the liver oxidant/antioxidant balance and on cytochrome-P450-mediated detoxication in rats. Animals were infused for 5 d with standard total parenteral nutrition (TPN), glutamine-enriched TPN, or alanyl glutamine-enriched TPN. The hepatic concentration of glutathione was reduced, and the levels of thiobarbituric-acid-reactive substances (TBARS) were increased in animals receiving standard TPN. Both glutamine and alanyl glutamine supplementation normalized glutathione, but thiobarbituric-acid-reactive substance concentration was only decreased by alanyl glutamine. This effect was parallel to a partial recovery of the activity of antioxidant enzymes. Cytochrome-P450 liver content, cytochrome-P450-dependent monooxygenases, and antipyrine clearance were not modified by glutamine or alanyl glutamine. Our data suggest a better protection against free radicals by alanyl glutamine supplementation and an absence of effects of both glutamine and alanyl glutamine on liver oxidative metabolism.

Growth hormone treatment prevents the decrease in insulin-like growth factor I gene expression in patients undergoing abdominal surgery.

Acquired GH resistance together with reduced skeletal muscle mass are found in patients with increased protein catabolism due, for example, to sepsis, trauma, or major surgery. Both administration of glutamine-containing parenteral nutrition and GH treatment have been found to diminish this catabolism. The effects of GH are mediated in part by insulin-like growth factor I (IGF-I) that is produced in the liver and locally in GH target tissues. The aim of this study was to investigate the effect of GH treatment on expression of the IGF-I gene and GH receptor (GHR) gene in skeletal muscle after major surgery. A new quantitative RT-PCR-based assay was established to measure IGF-I gene expression. Metabolically healthy patients, without significant preoperative weight loss, who were undergoing elective abdominal surgery were included in the study. Five patients (one woman and four men) were treated with daily injections of GH (0.3 IU/kg.day) in addition to being given total parenteral nutrition including glutamine (0.28 g/kg.day). The control group consisted of eight patients (three women and five men), who were given glutamine-enriched total parenteral nutrition but no GH. A muscle biopsy was taken from the lateral portion of the quadriceps femoris muscle preoperatively (day 0) after induction of anesthesia. A second biopsy was taken under local anesthesia on postoperative day 3. Total ribonucleic acid (RNA) was extracted from the muscle biopsies, and IGF-I messenger RNA (mRNA) and GHR mRNA were measured by competitive quantitative RT-PCR assays. IGF-I mRNA and GHR mRNA levels were related to the expression of a housekeeping gene (cyclophilin). In the control group, IGF-I mRNA levels decreased from 1505 +/- 265 (mean +/- SEM) transcripts/cpm cyclophilin on day 0 to 828 +/- 172 on day 3 (P < 0.05). In contrast, IGF-I mRNA levels did not change in the GH-treated group (1188 +/- 400 transcripts/cpm cyclophilin on day 0 vs. 1089 +/- 342 transcripts/cpm cyclophilin on day 3). No statistically significant changes were seen in GHR expression. We conclude that administration of GH prevents the reduction in IGF-I gene expression in skeletal muscle after abdominal surgery.

Effect of glutamine-enriched total parenteral nutrition on small intestinal gut-associated lymphoid tissue and upper respiratory tract immunity

Background. Our prior work shows that total parenteral nutrition (TPN) causes small intestinal gut-associated lymphoid tissue (GALT) atrophy, lowers small intestinal immunoglobulin A (IgA) levels, and impairs secretory IgA-mediated mucosal immunity of the upper respiratory tract. These experiments examine whether an isonitrogenous 2% glutamine-enriched TPN solution prevents these changes. Methods. Institute of Cancer Research mice were randomized to chow (chow), intravenous feeding of a TPN solution (TPN), or glutamine-enriched TPN (glutamine) groups. After mice were fed for 5 days, lymphocytes were isolated from Peyer's patches, the intraepithelial layer, and lamina propria to determine cell yields and phenotypes. Total small intestinal IgA levels were analyzed by means of enzyme-linked immunosorbent assay. In a second series of experiments, mice underwent intranasal inoculation with H1N1 virus to establish immunity. After 3 weeks mice were randomized to chow, TPN, or glutamine groups. After feeding for 5 days, mice were rechallenged with intranasal virus and killed at 40 hours to determine viral shedding from the upper respiratory tract. Results. Total lymphocyte yield in the Peyer's patches, the intraepithelial layer, and lamina propria, small intestinal IgA levels, and the CD4+ CD8+ ratio in the lamina propria decreased with TPN but remained normal with glutamine. On rechallenge, 87% of the mice in the TPN group shed virus in nasal secretions, whereas only 38% of the glutamine-treated group (p < 0.05 versus TPN) and 7.1% of the chow group (p < 0.002 versus TPN) were virus positive. Conclusions. Isonitrogenous supplementation of TPN with 2% glutamine improves IgA-mediated protection in the upper respiratory tract and normalizes GALT populations.

A prospective randomized study of glutamine-enriched parenteral compared with enteral feeding in postoperative patients

Plasma amino acids were measured in 17 postoperative subjects randomly assigned to receive for > or = 5 d tube feeding or total parenteral nutrition (TPN) that had identical energy, nitrogen, and glutamine contents. Subjects required gastric or pancreatic surgery for malignancy and were well-matched for age and body mass index. Tube feeding or TPN began on postoperative day 1 and advanced in daily 25% increments to meet goals of 105 kJ . kg body wt-1 . d-1, 1.5 g protein . kg body wt-1 . d-1, and 0.3 g glutamine . kg body wt-1 . d-1. Delivered energy, nitrogen, and glutamine were closely matched on day 4. Nitrogen balance and plasma proteins did not differ significantly between feeding groups. Total indispensable amino acids, branched-chain amino acids, and glutamine declined 25% on postoperative day 1 compared with preoperative day 0. Indispensable and branched-chain amino acid concentrations were restored with 5 d of either tube feeding or TPN. Glutamine concentrations did not differ significantly by feeding group, though a trend suggested that glutamine recovered more slowly in the tube-fed than in the TPN-fed subjects. Plasma amino acids otherwise reflected formula composition with ratios of valine to leucine of 1.24 and 3.69 mumol/L in subjects receiving 5 d of tube feeding or TPN, respectively. These findings suggest that glutamine-enriched tube feeding and TPN can result in similar profiles for most plasma amino acids at carefully matched doses.

Alanyl-glutamine-supplemented total parenteral nutrition improves survival and protein metabolism in rat protracted bacterial peritonitis model.

The effects of glutamine-enriched total parenteral nutrition (TPN) solution on survival, and protein turnover in the whole body and in individual organs were investigated in a rat protracted peritonitis model. Twenty-three rats underwent venous catheter insertion. Osmotic pumps were implanted in the peritoneal cavity to allow continuous delivery of Escherichia coli (4 x 10(8) CFU/d). The conventional TPN group received a conventional amino acid solution. The Ala-Gln TPN group received an alanyl-glutamine-enriched TPN solution. The two TPN solutions were isocaloric and isonitrogenous. Over the 5 days of TPN treatment, the survival rate of the Ala-Gln group was significantly higher than that of the conventional group. The Ala-Gln group tended to have increased whole-body protein turnover compared with the conventional group. Fractional protein synthetic rates (FSR) in the liver and gastrocnemius muscle of the Ala-Gln group were significantly higher than those of the conventional group. The serum glutamine concentration correlated positively with the FSR of both liver and muscle. The Ala-Gln group showed significantly greater mucosal height and mitoses per crypt, in the small intestine, than did the conventional group. Our results suggested that, in comparison with standard glutamine-free TPN, Ala-Gln-supplemented TPN increases protein synthesis in the liver and skeletal muscle, protects the morphology of the intestinal mucosa, and improves survival in protracted bacterial peritonitis. Ala-Gln supplementation may be useful in septic patients.

DOES INTRAVENOUS GLUTAMINE PREVENT BACTERIAL TRANSLOCATION IN HEMORRHAGIC SHOCK?

Bacterial translocation across the gut wall may be associated with insult to the latter. In this situation, intestinal flora can enter the blood stream and lymph nodes and be transported to other organs. Glutamine is a nonessential amino acid not presently included in total parenteral nutrition (TPN) preparations. The use of glutamine-enriched TPN in the rat has resulted in a significant reduction in bacterial translocation. This study attempted to evaluate the role of glutamine in preventing bacterial translocation following hemorrhagic shock in a rat model. Forty Sprague-Dawley rats were equally divided into two groups. The controls were given TPN solution, while the treated group had glutamine instead of the standard alanine present in TPN. Hemorrhagic shock was induced in both groups and blood cultures were performed. Glutamine-treated rats did not show a significant difference in survival suggesting that it is of no particular value in severe hemorrhagic shock in rats.