Cardiac surgery is associated with a widespread inflammatory response, by an additional release of free radicals. Due to the importance of these patient’s nutritional status, the present study was designed to evaluate the effectiveness of supplementation with a combination of glutamine, β-hydroxy-β-methylbutyrate (HMB) and arginine in patients undergoing to the heart surgery.

The experiment was performed in 1 month (30 days) before cardiac surgery. patients were asked to take 2 sachets of Heallagen® (a combination of 7 g l-arginine, 7 g l-glutamine, and 1.5 g daily HMB) or placebo with identical appearance and taste (maltodextrin) with 120 cc of water. Clinical and biochemical factors were evaluated in the baseline and end of the study.

Totally, 60 preoperative patients (30 interventions and 30 placeboes) with a mean age of 53.13 ± 14.35 years participated in the study. Subjects in Heallagen® group had a lower serum levels of interleukin-6 (P = 0.023), erythrocyte sedimentation rate (P < 0.01), high sensitivity C-reactive protein (P < 0.01), and lymphocyte number (P = 0.007) compared to the placebo, at end of the study.

In the patients undergoing heart surgery, Heallagen® significantly improved some of the inflammatory factors and hematological parameters. These results need to be confirmed in a larger trial.

Trial registration: The protocol of the study was registered in the IRCT.ir with registration no. IRCT20120913010826N31 at 13/10/2020.

• Arginine
• Beta-hydroxy-beta-methylbutyrate
• Glutamine
• HMB
• Heart surgery

• glutamine
• hypermetabolic and hypercatabolic syndrome
• parenteral nutrition
• surgical ICU patients

Under stress conditions, the metabolic demand for nutrients increases, which, if not met, may slow down or indeed stop the wound from healing, thus, becoming chronic wounds. This study aims to perform a systematic review and meta-analysis of the effect of arginine and glutamine supplementation on wound healing. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed for the systematic review and ten electronic databases were used. Five and 39 human studies met the inclusion criteria for arginine and glutamine, respectively. The overall meta-analysis demonstrated a significant effect of arginine supplementation on hydroxyproline content (MD: 4.49, 95% CI: 3.54, 4.45, p < 0.00001). Regarding glutamine supplementation, there was significant effect on nitrogen balance levels (MD: 0.39, 95% CI: 0.21, 0.58, p < 0.0001), IL-6 levels (MD: −5.78, 95% CI: −8.71, −2.86, p = 0.0001), TNFα levels (MD: −8.15, 95% CI: −9.34, −6.96, p < 0.00001), lactulose/mannitol (L/M) ratio (MD: −0.01, 95% CI: −0.02, −0.01, p < 0.00001), patient mortality (OR: 0.48, 95% CI: 0.32, 0.72, p = 0.0004), C-reactive protein (CRP) levels (MD: −1.10, 95% CI: −1.26, −0.93, p < 0.00001) and length of hospital stay (LOS) (MD: −2.65, 95% CI: −3.10, −2.21, p < 0.00001). Regarding T-cell lymphocytes, a slight decrease was observed, although it failed to reach significance (MD: −0.16, 95% CI: −0.33, 0.01, p = 0.07). Conclusion: The wound healing might be enhanced in one or at various stages by nutritional supplementation in the right dose.

• arginine
• collagen deposition
• contraction
• food
• glutamine
• growth factor
• gut permeability
• interleukin
• re-epithelialization
• wound healing

• Glutamina. Nutrición parenteral. Pacientes quirúrgicos críticos. Metaanálisis.

• Critical care nutrition
• Enteral nutrition
• Metabolic stress response
• Nutritional risk
• Parenteral nutrition
• Permissive underfeeding
• Supplemental parenteral nutrition
• Trophic feeding

• ERAS
• Enteral nutrition
• Parenteral nutrition
• Perioperative nutrition
• Prehabilitation
• Surgery

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.

Intravenous (i.v.) glutamine supplementation of parenteral nutrition (PN) can improve clinical outcomes, reduce mortality and infection rates and shorten the length of hospital and/or intensive care unit (ICU) stays compared with standard PN. This study is a pharmacoeconomic analysis to determine whether i.v. glutamine supplementation of PN remains both a highly favourable and cost-effective option for Italian ICU patients.

A previously published discrete event simulation model was updated by incorporating the most up-to-date and clinically relevant efficacy data (a clinically realistic subgroup analysis from a published meta-analysis), recent cost data from the Italian health-care system and the latest epidemiology data from a large Italian ICU database (covering 230 Italian ICUs and more than 77 000 patients). Sensitivity analyses were performed to test the robustness of the results.

Parenteral glutamine supplementation can significantly improve ICU efficiency in Italy, as the additional cost of supplemented treatment is more than completely offset by cost savings in hospital care. Supplementation was more cost-effective (cost-effectiveness ratio (CER)=€35 165 per patient discharged alive) than standard, non-supplemented PN (CER=€40 156 per patient discharged alive), and it resulted in mean cost savings of €4991 per patient discharged alive or €1047 per patient admitted to the hospital. Sensitivity analyses confirmed the robustness of these results.

Alanyl-glutamine supplementation of PN is a clinically and economically attractive strategy for ICU patients in Italy and may be applicable to selected ICU patient populations in other countries.

• Adult
• Critical Illness/mortality
• Cross Infection/mortality
• Cross Infection/prevention & control
• Glutamine/administration & dosage
• Hospital Mortality
• Humans
• Intensive Care Units/statistics & numerical data
• Length of Stay/statistics & numerical data
• Numbers Needed To Treat
• Randomized Controlled Trials as Topic
• Respiration, Artificial/statistics & numerical data
• Surgical Procedures, Operative/mortality

• Adolescent
• Adult
• Alanine/administration & dosage
• Alanine/blood
• Alanine/metabolism
• Brain Injuries/diagnosis
• Brain Injuries/drug therapy
• Brain Injuries/metabolism
• Dipeptides/administration & dosage
• Dipeptides/blood
• Dipeptides/metabolism
• Female
• Glutamic Acid/blood
• Glutamic Acid/metabolism
• Glutamine/administration & dosage
• Glutamine/blood
• Glutamine/metabolism
• Humans
• Infusions, Intravenous
• Male
• Middle Aged
• Severity of Illness Index
• Young Adult

The use of glutamine as a dietary supplement is associated with a reduced risk of infection. We hypothesized that the underlying mechanism could be an increase in the expression and/or functionality of Toll-like receptors (TLR), key receptors sensing infections. The objective of this study was to evaluate whether glutamine supplementation alters the expression and functionality of TLR2 and TLR4 in circulating monocytes of trauma patients admitted to the intensive care unit (ICU).

We designed a prospective, randomized and single-blind study. Twenty-three patients received parenteral nutrition (TPN) with a daily glutamine supplement of 0.35 g/kg. The control group (20 patients) received an isocaloric-isonitrogenated TPN. Blood samples were extracted before treatment, at 6 and 14 days. Expression of TLR2 and TLR4 was determined by flow cytometry. Monocytes were stimulated with TLR specific agonists and cytokines were measured in cell culture supernatants. Phagocytic ability of monocytes was also determined.

Basal characteristics were similar in both groups. Monocytes from patients treated with glutamine expressed the same TLR2 levels as controls before treatment (4.9 ± 3.5 rmfi vs. 4.3 ± 1.9 rmfi, respectively; P = 0.9), at Day 6 (3.8 ± 2.3 rmfi vs. 4.0 ± 1.7 rmfi, respectively; P = 0.7) and at Day 14 (4.1 ± 2.1 rfim vs. 4.6 ± 1.9 rmfi, respectively; P = 0.08). TLR4 levels were not significantly different between the groups before treatment: (1.1 ± 1 rmfi vs 0.9 ± 0.1 rmfi respectively; P = 0.9), at Day 6 (1.1 ± 1 rmfi vs. 0.7 ± 0.4 rmfi respectively; P = 0.1) and at Day 14 (1.4 ± 1.9 rmfi vs. 1.0 ± 0.6 rmfi respectively; P = 0.8). No differences in cell responses to TLR agonists were found between groups. TLR functionality studied by phagocytosis did not vary between groups.

In trauma patients in the intensive care unit, TPN supplemented with glutamine does not improve the expression or the functionality of TLRs in peripheral blood monocytes.

ClinicalTrials.gov Identifier: NCT01250080.

• amino acid metabolism (first pass)
• amino acids
• branched-chain amino acids (BCAA)
• dipeptide

In surgery, indications for artificial nutrition comprise prevention and treatment of catabolism and malnutrition. Thus in general, food intake should not be interrupted postoperatively and the re-establishing of oral (e.g. after anastomosis of the colon and rectum, kidney transplantation) or enteral food intake (e.g. after an anastomosis in the upper gastrointestinal tract, liver transplantation) is recommended within 24 h post surgery. To avoid increased mortality an indication for an immediate postoperatively artificial nutrition (enteral or parenteral nutrition (PN)) also exists in patients with no signs of malnutrition, but who will not receive oral food intake for more than 7 days perioperatively or whose oral food intake does not meet their needs (e.g. less than 60–80%) for more than 14 days. In cases of absolute contraindication for enteral nutrition, there is an indication for total PN (TPN) such as in chronic intestinal obstruction with a relevant passage obstruction e.g. a peritoneal carcinoma. If energy and nutrient requirements cannot be met by oral and enteral intake alone, a combination of enteral and parenteral nutrition is indicated. Delaying surgery for a systematic nutrition therapy (enteral and parenteral) is only indicated if severe malnutrition is present. Preoperative nutrition therapy should preferably be conducted prior to hospital admission to lower the risk of nosocomial infections. The recommendations of early postoperative re-establishing oral feeding, generally apply also to paediatric patients. Standardised operative procedures should be established in order to guarantee an effective nutrition therapy.

• fast track surgery
• postoperative nutrition
• surgery
• transplantation

• Aged
• Amino Acids/physiology
• Cardiopulmonary Bypass/methods
• Double-Blind Method
• Female
• Glutamine/administration & dosage
• Glutathione/blood
• Humans
• Intensive Care Units
• Length of Stay
• Male
• Multiple Organ Failure/blood
• Oxidative Stress/drug effects
• Perioperative Care/methods
• Treatment Outcome

Mortality rates in the Intensive Care Unit and subsequent hospital mortality rates in the UK remain high. Infections in Intensive Care are associated with a 2–3 times increased risk of death. It is thought that under conditions of severe metabolic stress glutamine becomes "conditionally essential". Selenium is an essential trace element that has antioxidant and anti-inflammatory properties. Approximately 23% of patients in Intensive Care require parenteral nutrition and glutamine and selenium are either absent or present in low amounts. Both glutamine and selenium have the potential to influence the immune system through independent biochemical pathways. Systematic reviews suggest that supplementing parenteral nutrition in critical illness with glutamine or selenium may reduce infections and mortality. Pilot data has shown that more than 50% of participants developed infections, typically resistant organisms. We are powered to show definitively whether supplementation of PN with either glutamine or selenium is effective at reducing new infections in critically ill patients.

2 × 2 factorial, pragmatic, multicentre, double-blind, randomised controlled trial. The trial has an enrolment target of 500 patients. Inclusion criteria include: expected to be in critical care for at least 48 hours, aged 16 years or over, patients who require parenteral nutrition and are expected to have at least half their daily nutritional requirements given by that route.

Allocation is to one of four iso-caloric, iso-nitrogenous groups: glutamine, selenium, both glutamine & selenium or no additional glutamine or selenium. Trial supplementation is given for up to seven days on the Intensive Care Unit and subsequent wards if practicable. The primary outcomes are episodes of infection in the 14 days after starting trial nutrition and mortality. Secondary outcomes include antibiotic usage, length of hospital stay, quality of life and cost-effectiveness.

To date more than 285 patients have been recruited to the trial from 10 sites in Scotland. Recruitment is due to finish in August 2008 with a further six months follow up. We expect to report the results of the trial in summer 2009.

This trial is registered with the International Standard Randomised Controlled Trial Number system. ISRCTN87144826

• G0401633 Medical Research Council
• HERU1 Chief Scientist Office
• HERU2 Chief Scientist Office
• HSRU1 Chief Scientist Office

• Ampulla of Vater/surgery
• Common Bile Duct Neoplasms/surgery
• Dietary Supplements
• Double-Blind Method
• Female
• Glutamine/therapeutic use
• Humans
• Male
• Middle Aged
• Pancreaticoduodenectomy
• Postoperative Complications/epidemiology
• Postoperative Complications/prevention & control
• Prospective Studies
• Treatment Outcome

• Critical Care/methods
• Critical Illness/mortality
• Critical Illness/therapy
• Glutamine/blood
• Glutamine/therapeutic use
• Humans
• Nitrogen/metabolism
• Nutritional Physiological Phenomena
• Parenteral Nutrition
• Randomized Controlled Trials as Topic

• G0401633 Medical Research Council
• HSRU1 Chief Scientist Office

AIM: To assess the clinical and economical validity of glutamine dipeptide supplemented to parenteral nutrition (PN) in patients undergoing abdominal surgery.

METHODS: A meta-analysis of all the relevant randomized controlled trials (RCTs) was performed. The trials compared the standard PN and PN supplemented with glutamine dipeptide in abdominal surgery. RCTs were identified from the following electronic databases: the Cochrane Library, MEDLINE, EMBASE and ISI web of knowledge (SCI). The search was undertaken in April 2006. Literature references were checked by computer or hand at the same time. Clinical trials were extracted and evaluated by two reviewers independently. Statistical analysis was performed by RevMan4.2 software from Cochrane Collaboration. A P value of < 0.05 was considered statistically significant.

RESULTS: Nine RCTs involving 373 patients were included. The combined results showed that glutamine dipeptide has a positive effect in improving postoperative cumulative nitrogen balance (weighted mean difference (WMD = 8.35, 95% CI [2.98, 13.71], P = 0.002), decreasing postoperative infectious morbidity (OR = 0.24, 95% CI [0.06, 0.93], P = 0.04), shortening the length of hospital stay (WMD= -3.55, 95% CI [-5.26, -1.84], P < 0.00001). No serious adverse effects were found.

CONCLUSION: Postoperative PN supplemented with glutamine dipeptide is effective and safe to decrease the infectious rate, reduce the length of hospital stay and improve nitrogen balance in patients undergoing abdominal surgery. Further high quality trials in children and severe patients are required, and mortality and hospital cost should be considered in future RCTs with sufficient size and rigorous design.

• Glutamine dipeptide
• Parenteral nutrition
• Abdominal surgery
• Meta-analysis

• Abdomen/surgery
• Dietary Supplements
• Dipeptides/administration & dosage
• Humans
• Parenteral Nutrition/methods
• Randomized Controlled Trials as Topic

• Animals
• Atrophy/etiology
• Dietary Supplements
• Glutamine/physiology
• Glutamine/therapeutic use
• Humans
• Intestinal Mucosa/pathology
• Intestinal Mucosa/physiopathology
• Intestine, Small/pathology
• Intestine, Small/physiopathology
• Parenteral Nutrition/adverse effects
• Stress, Physiological/drug therapy
• Stress, Physiological/physiopathology
• Treatment Outcome

• Adult
• Aged
• Dipeptides/administration & dosage
• Dipeptides/chemistry
• Dipeptides/metabolism
• Dipeptides/pharmacokinetics
• Dipeptides/urine
• Double-Blind Method
• Female
• Humans
• Hydrolysis
• Infusions, Intravenous
• Injections, Intraventricular
• Intensive Care Units
• Kinetics
• Male
• Middle Aged
• Placebos
• Time Factors

• Adult
• Aged
• Aged, 80 and over
• Chromatography, High Pressure Liquid
• Chromatography, Ion Exchange
• Critical Care
• Dose-Response Relationship, Drug
• Female
• Glutamine/administration & dosage
• Glutamine/blood
• Glutamine/pharmacology
• Humans
• Infusions, Intravenous
• Intensive Care Units
• Lactic Acid/analysis
• Male
• Middle Aged
• Muscle, Skeletal/drug effects
• Nitrogen/urine
• Prospective Studies
• Single-Blind Method
• Sulfhydryl Compounds/analysis
• Treatment Outcome

• Burns/drug therapy
• Burns/metabolism
• Glutamine/blood
• Glutamine/metabolism
• Glutamine/therapeutic use
• Humans
• Nutritional Support

• Critical Care
• Dipeptides/administration & dosage
• Dipeptides/therapeutic use
• Female
• Glutamine/blood
• Hospital Mortality
• Humans
• Intensive Care Units
• Length of Stay
• Male
• Middle Aged
• Parenteral Nutrition, Total
• Postoperative Care
• Treatment Outcome

• Critical Care
• Glutamine/therapeutic use
• Hospital Mortality
• Humans
• Information Storage and Retrieval
• Length of Stay
• Parenteral Nutrition
• Postoperative Care
• Randomized Controlled Trials as Topic

• Amino Acids
• Energy Metabolism
• Humans
• Nitrogen
• Nutritional Requirements

• Clinical Trials as Topic
• Conflict of Interest
• Humans
• Nutritional Physiological Phenomena

• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Bone Marrow Transplantation
• Clinical Trials as Topic
• Combined Modality Therapy
• Diarrhea/prevention & control
• Dietary Supplements
• Disease Models, Animal
• Enteral Nutrition
• Glutamine/administration & dosage
• Humans
• Infusions, Intravenous
• Neoplasms/drug therapy
• Neoplasms/therapy
• Parenteral Nutrition, Total

• M01 RR00039 NCRR NIH HHS
• R01 DK55850 NIDDK NIH HHS