Glutamine Dipeptide Supplementation Research Articles

Glutamine dipeptide-supplemented parenteral nutrition improves the clinical outcomes of critically ill patients: A systematic evaluation of randomised controlled trials

Early randomised controlled trials (RCTs) testing whether parenteral nutrition regimens that include glutamine dipeptides improves the outcomes of critically ill patients demonstrated convincingly that this regimen associates with reduced mortality, infections, and hospital stays. However, several new RCTs on the same question challenged this. To resolve this controversy, the present meta-analysis was performed. Stringent eligibility criteria were used to select only those RCTs that tested the outcomes of critically ill adult patients without hepatic and/or renal failure who were haemodynamically and metabolically stabilised and who were administered glutamine dipeptide strictly according to current clinical guidelines (via the parenteral route at 0.3-0.5g/kg/day; max. 30% of the prescribed nitrogen supply) in combination with adequate nutrition. The literature research (PubMed, Embase, Cochrane Central Register of Controlled Trials) searched for English and German articles that had been published in peer-review journals (last entry March 31, 2015) and reported the results of RCTs in critically ill adult patients (major surgery, trauma, infection, or organ failure) who received parenteral glutamine dipeptide as part of an isoenergetic and isonitrogenous nutrition therapy. The following data were extracted: infectious complications, lengths of stay (LOS) in the hospital and intensive care unit (ICU), duration of mechanical ventilation, days on inotropic support, and ICU and hospital mortality rates. The selection of and data extraction from studies were performed by two independent reviewers. Fifteen RCTs (16 publications) fulfilled all selection criteria. They involved 842 critically ill patients. None had renal and/or hepatic failure. The average study quality (Jadad score: 3.8 points) was well above the predefined cut-off of 3.0. Common effect estimates indicated that parenteral glutamine dipeptide supplementation significantly reduced infectious complications (relative risk [RR]=0.70, 95% CI 0.60, 0.83, p<0.0001), ICU LOS (common mean difference [MD]-1.61 days, 95% CI-3.17,-0.05, p=0.04), hospital LOS (MD-2.30 days, 95% CI-4.14,-0.45, p=0.01), and mechanical ventilation duration (MD-1.56 days, 95% CI-2.88,-0.24, p=0.02). It also lowered the hospital mortality rate by 45% (RR=0.55, 95% CI 0.32, 0.94, p=0.03) but had no effect on ICU mortality. Visual inspection of funnel plots did not reveal any potential selective reporting of studies. This meta-analysis clearly confirms that when critically ill patients are supplemented with parenteral glutamine dipeptide according to clinical guidelines as part of a balanced nutrition regimen, it significantly reduces hospital mortality, infectious complication rates, and hospital LOS. The latter two effects indicate that glutamine dipeptide supplementation also confers economic benefits in this setting. The present analysis indicates the importance of delivering glutamine dipeptides together with adequate parenteral energy and nitrogen so that the administered glutamine serves as precursor in various biosynthetic pathways rather than simply as a fuel.

Glutamine dipeptide supplementation improves clinical responses in patients with diabetic foot syndrome

The effect of glutamine dipeptide (GDP) supplementation in patients with diabetic foot syndrome was evaluated. A total of 22 patients took part in the study. GDP was supplied in 10 g sachets, and was dissolved in water immediately before use, with ingestion once a day, after lunch or after dinner (20 g/day) over a period of 30 days. Quantification of foot insensitive areas, oxidative stress, blood cytokines, and biochemical, hematological and toxicological parameters was performed before and after GDP supplementation. We observed an increase in blood levels of interferon-α (P=0.023), interferon-γ (P=0.038), interleukin-4 (P=0.003), interleukin-6 (P=0.0025), interleukin-7 (P=0.028), interleukin-12 p40 (P=0.017), interleukin-13 (P=0.001), leukocytes (P=0.037), eosinophils (P=0.049), and typical lymphocytes (P<0.001) due to GDP administration. In addition, we observed a reduced number (P=0.048) of insensitive areas on the foot, and reduction (P=0.047) of fasting hyperglycemia. Patients also showed increased blood high density lipoprotein (P<0.01) and protein thiol groups (P=0.004). These favorable results were associated with the absence of renal and hepatic toxicity. These results are of clinical relevance, since supplementation with GDP over 30 days improved clinical responses in patients with diabetic foot syndrome.

Effect of glutamine dipeptide supplementation on primary outcomes for elective major surgery: systematic review and meta-analysis.

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

Effectiveness of perioperative glutamine in parenteral nutrition in patients at risk of moderate to severe malnutrition.

To determine whether perioperative glutamine supplementation of parenteral nutrition (PN) has an impact on morbidity and mortality of patients with previous moderate to severe risk of malnutrition. A quasi-experimental study was conducted comparing the following groups: Control group 1: without glutamine dipeptide supplementation of PN during the perioperative period. Control group 2: PN was supplemented with glutamine dipeptide (0.4 g/kg/day) after surgery only. Group 3 (follow-up group): PN was supplemented with glutamine dipeptide (0.4 g/kg/day) in the perioperative period. Postoperative morbidity and mortality was recorded. Sixty-seven patients matched for baseline and surgical characteristics were recruited into the study. Univariate analysis showed a lower incidence of hyperglycemia and ICU admission in group 3, and a trend to significance (P = 0.078) in terms of a lower incidence of infection. In the multivariate analysis, only group 3 met the models of ICU admission (OR = 0.28), hyperglycemia (OR = 0.11), and renal failure (OR = 0.19). The results show that perioperative use of glutamine dipeptide in patients at risk of moderate to severe malnutrition before surgery is an effective option for decreasing the morbidity associated with malnutrition, as it improves blood glucose modulation and reduces infection and ICU stay.

Effect on immune indices of preoperative intravenous glutamine dipeptide supplementation in malnourished abdominal surgery patients in the preoperative and postoperative periods

Objective To determine if parenteral glutamine dipeptide supplementation given only in the preoperative period in malnourished patients after gastrointestinal surgery would sustain its effects into the first postoperative week, as shown by immune indices. Methods A prospective randomized study on malnourished adult patients for abdominal surgery was done where one group ( n = 17) received preoperative glutamine supplementation (0.3 g · kg −1 · d −1) for 5 d and the other ( n = 17) had none. Both received isocaloric (30 kcal · kg −1 · d −1) and isonitrogenous (1.5 g · kg −1 · d −1) nutrition. Outcomes were 1) immune indices on admission (day 1), the day before surgery (day 2), and the seventh postoperative day (day 3); and 2) clinical outcomes were infection, wound complication, days in the intensive care unit, and mortality. Statistical tests were repeated samples analysis of variance, Friedman's test, Wilcoxon's test, and t test for individual comparison. Results The glutamine-supplemented group showed an increase in total white blood cells (from 8700 on day to 11 080 on day 2, P = 0.026), granulocytes (from 6177 on day 1 to 8568 on day 2, P = 0.039), and lymphocytes (from 1516 on day 1 to 1747 on day 2, P = 0.049). Significant decreases in glutamine-supplemented group values from day 2 to day 3 occurred in granulocytes, lymphocytes, and CD8, CD22, and CD19 cells. Clinical outcome was similar in both groups. Intake was adequate in both groups (preoperative 85% versus postoperative 82% computed) and the mean glutamine delivered was 18 g/d. Conclusion Parenteral glutamine supplementation in the preoperative period resulted in increased white blood cell, granulocyte, and lymphocyte counts, which was not sustained in the first week of the postoperative period, when supplementation was discontinued before surgery.

Pilot Study: Effects of Parenteral Glutamine Dipeptide Supplementation on Neutrophil Functions and Prevention of Chemotherapy-Induced Side-Effects in Acute Myeloid Leukaemia Patients

The effect of parenteral glutamine dipeptide (Gln) supplementation on neutrophil phagocytosis, superoxide anion generation (SAG), prevention of chemotherapy-induced side-effects and cost-effectiveness was examined in a pilot study of acute myeloid leukaemia (AML) patients receiving chemotherapy. Sixteen AML patients were randomized to receive intravenous supplementation with Gln (30 g/day) or an equivalent quantity (25 g/day) of a standard amino acid mixture (control) on days 1 - 5 of chemotherapy. Complete blood count was evaluated twice a week until hospital discharge, and neutrophil phagocytosis and SAG were measured when absolute neutrophil count reached > 500 /microl. Patients were observed for development of infection, mucositis and diarrhoea. In Gln-treated patients, the percentage of neutrophil phagocytosis and the SAG levels were significantly higher than in control patients (20.5 +/- 6.0% and 18.9 +/- 2.9 nmol/10(6) neutrophils per 10 min, respectively). The Gln-treated patients lost significantly less weight, tended to have shorter in-patient duration and had less severe oral mucositis than controls. This pilot study provides preliminary indication that parenteral Gln supplementation enhances neutrophil phagocytic function, maintains nutritional status and is cost effective. Parenteral Gln may also prevent oral mucositis, although further studies involving more patients need to be undertaken to confirm this and the other results.

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

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

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

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

Glutamine attenuates TPN-associated liver injury in infant rabbits

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

Effect of total parenteral nutrition (TPN) with and without glutamine dipeptide supplementation on outcome in severe acute pancreatitis (SAP)

Objective: To investigate the effect of total parenteral nutrition (TPN) and glutamine-supplemented TPN in patients with serious acute pancreatitis (SAP). Methods: Sixty-four patients with SAP were randomly divided into three therapeutic groups. Twenty-three cases (group I) were treated by traditional therapeutic program combined with traditional therapy, the 21 cases in group II and 20 cases in group III were treated by TPN and glutamine-supplemented TPN, respectively. The concentration of serum albumin was determined, recovery time of blood amylase, the incidence of complications, mortality, length of hospital stay (LOS) and body mass of the patients in each group were monitored. Results: The concentrations of serum albumin were low in all three groups at admission. After 2 weeks of treatment, the serum albumin concentration increased in groups II and III, while it remained almost the same in group I. Mortalities for groups I, II, and III were 43.5% (10/23), 14.3% (3/21, vs. group I P<0.05) and 0% (vs. group I P<0.01), respectively. The incidence of complications in group I (21/23) was much higher than those in group II (11/21, P<0.01) and group III (4/20, P<0.01), and in group III they were less frequent than in group II (P<0.05). In fact no pancreatic infection occurred in group III with glutamine dipeptide supplementation. The loss of body mass in group I was more profound than in groups II and III, P<0.05. The length of stay (LOS) in group I (39.1±10.60 d) was longer than those of group II (28.6±6.90 d, P<0.05) and III (25.3±7.60 d, P<0.01). Conclusions: Combined with conventional therapy, TPN and glutamine dipeptide-supplemented TPN therapy can reduce mortality and the incidence of infectious complications, shorten the LOS, and improve the nutritional status of patients with SAP. Glutamine-supplemented TPN therapy can apparently prevent the occurrence of pancreatic infection.

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

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

Why should a single nutrient—glutamine—improve outcome?The remarkable story of glutamine dipeptides

Summary Recent knowledge about efficient utilization of intravenously supplied dipeptides has made it possible to supplement available amino acids solutions with stable, highly soluble glutamine-containing dipeptides. This novel approach has opened up a new dimension: today, glutamine-containing dipeptides are an integral part of the routine in clinical practice. In numerous controlled clinical trials it could be convincingly demonstrated that supplemental glutamine (dipeptide) nutrition was associated with improved nitrogen balance and mood; increased protein synthesis and lymphocyte count (total and subpopulation); maintained intestinal function; intracellular muscle free glutamine pool; gut permeability and function; and reduced 3-MeHis excretion. More importantly it could be demonstrated that glutamine (dipeptide) supplementation reduced the rate of infectious complications, length of hospital stay and mortality. Stable glutamine containing dipeptides introduced a new dimension in clinical glutamine research; at present these dipeptides are integral parts of routine clinical practice.

Glutamine dipeptide-supplemented parenteral nutrition in patients with colorectal cancer

Summary Objectve : To study the impact of glutamine-supplemented parenteral nutrition on immune-function and protein metabolism in postoperative patients with colorectal cancer. Methods : Forty colorectal cancer patients were randomized into two groups and were administered isonitrogenous and isocaloric parenteral nutrition with (ala-gln group) or without (TPN group) glutamine dipeptide (0.3–0.4g/kg –1 d –1 ) for 7 days postoperatively. Immune function and nitrogen balance were assessed peri-operatively. Results : Compared to a matched group of patients with gastrointestinal benign diseases (control group) colorectal cancer patients showed immune suppression preoperatively. Postoperatively, from the fourth day onwards CD4, NK cell counts, CD4/CD8 ratio and IL-2R expression were higher ( P Conclusions : Glutamine dipeptide supplementation improved immune-function and nitrogen balance in patients with colorectal cancer postoperatively.

The impact of glutamine dipeptides on outcome of surgical patients: systematic review of randomized controlled trials from Europe and Asia

Summary Introduction : We systematically reviewed the clinical efficacy of glutamine dipeptide supplementation in surgical patients from prospective randomized controlled clinical trials (RCTs) from Europe and Asia. Material and methods : Medline, SCI, Embase, Cochrane Library and the Chinese Biomedicine Database were searched for European and Asian studies published in 1996 or later, that were RCTs for elective surgical patients. Parenteral nutrition, with or without l-alanyl-l-glutamine dipeptides (ala–gln), or in one study with or without glycyl-l-glutamine (gly–gln) dipeptides, was the only difference between intervention and control groups. Methodological quality assessment was based on Cochrane Reviewers' Handbook and Jada's Score Scale. Statistical software RevMan4.2 was used for meta-analysis. The data were treated by intention-to-treat method. Results : A total of 1335 titles were screened. Thirteen studies met our inclusion–exclusion criteria. Impact on infectious complication: 10 studies (pooled n = 355 ) were analyzed. Ala–gln significantly reduced infectious complications. Pooled relative risk (RR) was 0.42 (95% CI 0.24–0.72; P = 0.002 ). Impact on the length of hospital stay (LOS): Five studies (pooled n = 179 ) met our criteria. Glutamine dipeptides significantly reduced LOS by a weighted mean difference of 3.86 days (95% CI −6.03 to −1.68d; P 0.00001 ). Conclusion : Parenteral glutamine dipeptides showed significant reduction in infectious morbidity and LOS in a meta-analysis of European and Asian RCTs in elective surgery patients.

The effect of glutamine-supplemented total parenteral nutrition on nitrogen economy depends on severity of diseases in surgical patients

Background: Gln is an important substrate for enterocyte and rapid proliferation cells. Studies have shown that parenteral supplementation of Gln maintains the intracellular Gln pool, improves nitrogen balance and shortens hospital stay. However, some studies showed Gln-supplemented TPN had no effect on restoring the Gln pool in critically ill patients. Objective: To evaluate the effect of glutamine (Gln) dipeptide supplementation of total parenteral nutrition (TPN) on postoperative nitrogen balance and immune response of patients undergoing surgery. Methods: This study is a prospective, randomized double-blind clinical trial. APACHE II score and TISS were used to evaluate the patients after admission. Forty-eight patients with major abdominal surgery were allocated to two groups to receive isonitrogenous (0.228 g nitrogen/kg/day) and isoenergetic (30 kcal/kg/day) TPN for 6 days. Two groups (Conv and Ala-Gln) were further divided to high (APACHE⩾6) and low (APACHE <6) groups. Control group (Conv) received 1.5 g amino acids/kg/day, whereas the Ala-Gln group received 0.972 g amino acids/kg/day and 0.417 g of L -alanyl- L -glutamine (Ala-Gln)/kg/day. Blood samples were collected on day 1 and day 6 after surgery for plasma amino acid and CD4, CD8 cell and T lymphocyte analysis. Cumulative nitrogen balance were also measured on day 2, 3, 4, 5 postoperatively. Results: Although there was a tendency to have better cumulative nitrogen balance on the postoperative days in the Ala-Gln group, no significant difference was observed between two groups. However, a better significant cumulative nitrogen balance was observed on the 2nd, 3rd and 5th postoperative day in the Ala-Gln group than in the Conv group in patients with APACHE II <6, whereas no significant difference was noted in patients with APACHE II ⩾ 6. No difference in urine 3-methylhistidine excretion were observed between the 2 groups. Patients in the Ala-Gln group had significant higher T lymphocyte and CD4 cells than did those in the Conv group.Conclusion: TPN supplemented with Gln dipeptide had beneficial effect on enhancing the immune response. However, the effect of Ala-Gln administration on improving nitrogen economy was only observed in patients with low APACHE II scores. These results may indicate that Gln required for reversing the catabolic condition may depend on the characteristics and severity of the diseases.

Glutamine dipeptide-supplemented parenteral nutrition reverses gut atrophy, disaccharidase enzyme activity, and absorption in rats.

Total parenteral nutrition (TPN) is associated with intestinal atrophy and dysfunction possibly attributed to the absence of the nonessential amino acid glutamine from commercially available TPN solutions because of the instability of the monoamino acid during heat sterilization and storage. The use of stable dipeptides may overcome this problem. In this study we tested the hypothesis that glutamine dipeptide supplementation with alanyl-L-glutamine during TPN for 10 days would reverse small bowel atrophy and TPN-induced dysfunction in rats. A conventional TPN solution (250 kcal/kg bw) was compared with an isocaloric and isonitrogenous TPN supplemented with alanyl-L-glutamine dipeptide. A food-fed control group was included (n = 6 each group). Jejunum mucosal architecture, absorption of water and glucose, and disaccharidase activity of maltase and alkaline phosphatase were evaluated. TPN-induced villous atrophy, significantly reduced absorption rate, and decreased activity of villous enzymes, compared with the TPN group, could be reversed by supplementation of glutamine dipeptide alanyl-L-glutamine to parenteral nutrition solutions with no difference to the control group. Glutamine dipeptide-enriched parenteral nutrition preserves mucosal structure and reversed atrophy-associated dysfunction.

Glutamine dipeptide-supplemented parenteral nutrition maintains intestinal function in the critically III

Background/Aims: Long-term total parenteral nutrition is accompanied with mucosal atrophy and subsequent malabsorption syndrome. Current information attests the important role of glutamine in maintaining intestinal structure and function. The aim of this study was to investigate the effect of glutamine dipeptide supplementation on small intestinal absorption capacity during critical illness. Methods: Twelve intensive care unit patients were uniformly randomized to receive isonitrogenous (0.26 g nitrogen·kg−1·day−1) and isoenergetic (155 kJ·kg−1·day−1) parenteral nutrition over 9 days. The control group received a conventional amino acid solution (1.5 g amino acids·kg−1·day−1), and the test group received a complete amino acid solution containing the dipeptide l-alanyl-l-glutamine (20 g/L). On days 8 and 9, a modified d-xylose test was performed. Results: Excretion of d-xylose during the 5-hour test period was 7.4 ± 1.1 g (test) vs. 3.8 ± 0.9 g (control) (P < 0.05). The 2-hour serum d-xylose concentration was 38.7 ± 3.0 (test) vs. 27.8 ± 2.9 mg/100 mL (control) (P < 0.05). Kinetic evaluation showed higher maximum d-xylose blood concentration and higher values for the area under the curve with the peptide. Conclusions: The results strongly suggest that glutamine dipeptide-containing total parenteral nutrition prevents intestinal atrophy and increased permeability associated with glutamine-free parenteral nutrition.