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Adachi H, Kudo M, Ishiyama S, Mochizuki K. Protein restriction during the fetal period upregulates IL1B and IL13 while suppressing MUC2 expression in the jejunum of mice after weaning. Nutrition 2022; 98:111605. [DOI: 10.1016/j.nut.2022.111605] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 01/13/2022] [Accepted: 01/17/2022] [Indexed: 11/15/2022]
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2
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Toni T, Alverdy J, Gershuni V. Re-examining chemically defined liquid diets through the lens of the microbiome. Nat Rev Gastroenterol Hepatol 2021; 18:903-911. [PMID: 34594028 PMCID: PMC8815794 DOI: 10.1038/s41575-021-00519-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/31/2021] [Indexed: 12/13/2022]
Abstract
Trends in nutritional science are rapidly shifting as information regarding the value of eating unprocessed foods and its salutary effect on the human microbiome emerge. Unravelling the evolution and ecology by which humans have harboured a microbiome that participates in every facet of health and disease is daunting. Most strikingly, the host habitat has sought out naturally occurring foodstuff that can fulfil its own metabolic needs and also the needs of its microbiota, each of which remain inexorably connected to one another. With the introduction of modern medicine and complexities of critical care, came the assumption that the best way to feed a critically ill patient is by delivering fibre-free chemically defined sterile liquid foods (that is, total enteral nutrition). In this Perspective, we uncover the potential flaws in this assumption and discuss how emerging technology in microbiome sciences might inform the best method of feeding malnourished and critically ill patients.
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Affiliation(s)
- Tiffany Toni
- University of Chicago, Pritzker School of Medicine, Chicago, IL, USA
| | - John Alverdy
- University of Chicago, Pritzker School of Medicine, Chicago, IL, USA
| | - Victoria Gershuni
- University of Pennsylvania, Department of Surgery, Philadelphia, PA, USA and Washington University in St Louis, Department of Surgery, St Louis, MO, USA,Corresponding author
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The Effect of Amino Acids on Wound Healing: A Systematic Review and Meta-Analysis on Arginine and Glutamine. Nutrients 2021; 13:nu13082498. [PMID: 34444657 PMCID: PMC8399682 DOI: 10.3390/nu13082498] [Citation(s) in RCA: 59] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Revised: 07/16/2021] [Accepted: 07/20/2021] [Indexed: 01/08/2023] Open
Abstract
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.
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Vanderhoof JA, Blackwood DJ, Mohammadpour H, Park JH. Effects of Oral Supplementation of Glutamine on Small Intestinal Mucosal Mass Following Resection. J Am Coll Nutr 2020. [DOI: 10.1080/07315724.1992.12098247] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Affiliation(s)
- Jon A. Vanderhoof
- Department of Pediatrics, Creighton University School of Medicine (J.A.V., J.H.Y.P.), Department of Pediatrics, University of Nebraska School of Medicine, The Center for Human Nutrition (J.A.V., D.J.B., H.M., J.H. Y.P.), Omaha
| | - Darcy J. Blackwood
- Department of Pediatrics, Creighton University School of Medicine (J.A.V., J.H.Y.P.), Department of Pediatrics, University of Nebraska School of Medicine, The Center for Human Nutrition (J.A.V., D.J.B., H.M., J.H. Y.P.), Omaha
| | - Hamid Mohammadpour
- Department of Pediatrics, Creighton University School of Medicine (J.A.V., J.H.Y.P.), Department of Pediatrics, University of Nebraska School of Medicine, The Center for Human Nutrition (J.A.V., D.J.B., H.M., J.H. Y.P.), Omaha
| | - Jung H.Y. Park
- Department of Pediatrics, Creighton University School of Medicine (J.A.V., J.H.Y.P.), Department of Pediatrics, University of Nebraska School of Medicine, The Center for Human Nutrition (J.A.V., D.J.B., H.M., J.H. Y.P.), Omaha
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Haba Y, Fujimura T, Oyama K, Kinoshita J, Miyashita T, Fushida S, Harada S, Ohta T. Effect of Oral Branched-Chain Amino Acids and Glutamine Supplementation on Skeletal Muscle Atrophy After Total Gastrectomy in Rat Model. J Surg Res 2019; 243:281-288. [DOI: 10.1016/j.jss.2019.05.041] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Revised: 05/20/2019] [Accepted: 05/29/2019] [Indexed: 01/03/2023]
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Metabolic Differences between Dogs of Different Body Sizes. J Nutr Metab 2017; 2017:4535710. [PMID: 29225968 PMCID: PMC5684564 DOI: 10.1155/2017/4535710] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Accepted: 09/25/2017] [Indexed: 01/05/2023] Open
Abstract
Introduction The domesticated dog, Canis lupus familiaris, has been selectively bred to produce extreme diversity in phenotype and genotype. Dogs have an immense diversity in weight and height. Specific differences in metabolism have not been characterized in small dogs as compared to larger dogs. Objectives This study aims to identify metabolic, clinical, and microbiota differences between small and larger dogs. Methods Gas chromatography/mass spectrometry, liquid chromatography/tandem mass spectrometry, clinical chemistry analysis, dual-energy X-ray absorptiometry, and 16S pyrosequencing were used to characterize blood metabolic, clinical, and fecal microbiome systems, respectively. Eighty-three canines from seven different breeds, fed the same kibble diet for 5 weeks, were used in the study. Results 449 metabolites, 16 clinical parameters, and 6 bacteria (at the genus level) were significantly different between small and larger dogs. Hierarchical clustering of the metabolites yielded 8 modules associated with small dog size. Conclusion Small dogs had a lower antioxidant status and differences in circulating amino acids. Some of the amino acid differences could be attributed to differences in microflora. Additionally, analysis of small dog metabolites and clinical parameters reflected a network which strongly associates with kidney function.
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Wilmore DW. Food and Drug Administration Approval of Glutamine for Sickle Cell Disease: Success and Precautions in Glutamine Research. JPEN J Parenter Enteral Nutr 2017; 41:912-917. [PMID: 28858569 DOI: 10.1177/0148607117727271] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Rai VRH, Phang LF, Sia SF, Amir A, Veerakumaran JS, Kassim MKA, Othman R, Tah PC, Loh PS, Jailani MIO, Ong G. Effects of immunonutrition on biomarkers in traumatic brain injury patients in Malaysia: a prospective randomized controlled trial. BMC Anesthesiol 2017; 17:81. [PMID: 28619005 PMCID: PMC5472912 DOI: 10.1186/s12871-017-0369-4] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2016] [Accepted: 05/31/2017] [Indexed: 11/27/2022] Open
Abstract
Background Head injury is one of the top three diagnosis leading to intensive care unit (ICU) admission in Malaysia. There has been growing interest in using immunonutrition as a mode of modulating the inflammatory response to injury or infection with the aim of improving clinical outcome. The aim of the present study was to evaluate the effect of an immunonutrition on biomarkers (IL-6, glutathione, CRP, total protein and albumin) in traumatic brain injury patients. Methods Thirty six patients with head injury admitted to neurosurgical ICU in University Malaya Medical Centre were recruited for this study, over a 6-month period from July 2014 to January 2015. Patients were randomized to receive either an immunonutrition (Group A) or a standard (Group B) enteral feed. Levels of biomarkers were measured at day 1, 5 and 7 of enteral feeding. Results Patients in Group A showed significant reduction of IL-6 at day 5 (p < 0.001) with concurrent rise in glutathione levels (p = 0.049). Patients in Group A also demonstrated a significant increase of total protein level at the end of the study (day 7). Conclusion These findings indicate the potential of immunonutrition reducing cytokines and increasing antioxidant indices in patients with TBI. However, further studies incorporating patient outcomes are needed to determine its overall clinical benefits. Trial registration National Medical Research Register (NMRR) ID: 14–1430-23,171. ClinicalTrials.gov identifier: NCT03166449.
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Affiliation(s)
- Vineya Rai Hakumat Rai
- School of Medicine, Taylor's University, Lakeside Campus, 47500, Subang Jaya, Malaysia.,KPJ Tawakkal Specialist Hospital, Jalan Pahang Barat, 53000, Kuala Lumpur, Malaysia
| | - Lee Fern Phang
- Department of Anaesthesiology, Hospital Umum Sarawak, Jalan Hospital, 93586, Kuching, Sarawak, Malaysia
| | - Sheau Fung Sia
- Division of Neurosurgery, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | - Amirah Amir
- Department of Parasitology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
| | - Jeyaganesh S Veerakumaran
- Department of Anaesthesiology, Faculty of Medicine, University Malaya, 50603, Kuala Lumpur, Malaysia
| | | | - Rafidah Othman
- Department of Dietetics, University Malaya Medical Centre, 50603, Kuala Lumpur, Malaysia
| | - Pei Chien Tah
- Department of Dietetics, University Malaya Medical Centre, 50603, Kuala Lumpur, Malaysia
| | - Pui San Loh
- Department of Anaesthesiology, Faculty of Medicine, University Malaya, 50603, Kuala Lumpur, Malaysia
| | | | - Gracie Ong
- Department of Anaesthesiology, Faculty of Medicine, University Malaya, 50603, Kuala Lumpur, Malaysia
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Borel MJ, Williams PE, Jabbour K, Flakoll PJ. Chronic Hypocaloric Parenteral Nutrition Containing Glutamine Promotes Hepatic Rather Than Skeletal Muscle or Gut Uptake of Glutamine After Fasting. JPEN J Parenter Enteral Nutr 2016. [DOI: 10.1177/014860719602000105] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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Tamada H, Nezu R, Imamura I, Matsuo Y, Takagi Y, Kamata S, Okada A. The Dipeptide Alanyl-Glutamine Prevents Intestinal Mucosal Atrophy in Parenterally Fed Rats. JPEN J Parenter Enteral Nutr 2016; 16:110-6. [PMID: 1372946 DOI: 10.1177/0148607192016002110] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
This study was performed to determine whether the addition of alanyl-glutamine (Ala-Gln) can prevent intestinal mucosal atrophy induced by standard solution of total parenteral nutrition (S-TPN). Forty-one male Sprague-Dawley rats weighing 250 g were randomly divided into four groups: group I was killed after overnight fasting; group II received S-TPN. The other groups received S-TPN supplemented with amino acids other than glutamine (group III) or supplemented with Ala-Gln 2 g/100 mL (group IV); both solutions were isocaloric and isonitrogenous. After 1 week of TPN the rats were killed, and the duodenum, proximal jejunum, mid-small bowel, and distal ileum were obtained for morphologic and functional analysis. Weight gain did not differ significantly among these four groups, and there was no difference in nitrogen balance between groups III and IV. Serum glutamine in group IV (102.8 +/- 13.3 mumol/dL) was significantly increased (p less than .05) compared with groups I, II, and III (66.2 +/- 3.9, 55.7 +/- 7.8, and 61.3 +/- 10.8 mumol/dL, respectively). Mucosal wet weight, protein, RNA, sucrase, and maltase of group IV were significantly increased (p less than .05) compared with groups II and III. Villus height was significantly increased (p less than .05) in the jejunum of group IV rats compared with groups II and III, but not in any other segments of the intestine. No significant changes were observed in crypt depth among all groups. Diamine oxidase in groups II, III, and IV was significantly decreased (p less than .05) compared with group I in all segments except for the ileum.(ABSTRACT TRUNCATED AT 250 WORDS)
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Affiliation(s)
- H Tamada
- Department of Pediatric Surgery, Osaka University Medical School, Japan
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Moe‐Byrne T, Brown JVE, McGuire W. Glutamine supplementation to prevent morbidity and mortality in preterm infants. Cochrane Database Syst Rev 2016; 4:CD001457. [PMID: 27089158 PMCID: PMC7055588 DOI: 10.1002/14651858.cd001457.pub6] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
BACKGROUND 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. OBJECTIVES To determine the effects of glutamine supplementation on mortality and morbidity in preterm infants. SEARCH METHODS 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. SELECTION CRITERIA 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. DATA COLLECTION AND ANALYSIS 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. MAIN RESULTS 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. AUTHORS' CONCLUSIONS The available trial data do not provide evidence that glutamine supplementation confers important benefits for preterm infants.
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Affiliation(s)
| | | | - William McGuire
- Hull York Medical School & Centre for Reviews and Dissemination, University of YorkYorkY010 5DDUK
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12
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Moe-Byrne T, Brown JVE, McGuire W. Glutamine supplementation to prevent morbidity and mortality in preterm infants. Cochrane Database Syst Rev 2016:CD001457. [PMID: 26755330 DOI: 10.1002/14651858.cd001457.pub5] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
BACKGROUND 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. OBJECTIVES To determine the effects of glutamine supplementation on mortality and morbidity in preterm infants. SEARCH METHODS 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. SELECTION CRITERIA 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. DATA COLLECTION AND ANALYSIS 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. MAIN RESULTS 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. AUTHORS' CONCLUSIONS The available trial data do not provide evidence that glutamine supplementation confers important benefits for preterm infants.
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Salman AE, Yetişir F, Kılıç M, Onal O, Dostbil A, Zeybek D, Aksoy M, Kaymak F, Celik T, Unver S. The impact of pretreatment with bolus dose of enteral glutamine on acute lung injury induced by oleic acid in rats. J Anesth 2014; 28:354-62. [PMID: 24271996 DOI: 10.1007/s00540-013-1745-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2013] [Accepted: 10/30/2013] [Indexed: 01/29/2023]
Abstract
PURPOSE Both parenteral and enteral glutamine have shown beneficial effects in sepsis and ischemia/reperfusion-induced acute lung injury (ALI). Oleic acid (OA) has been used to induce ALI in experimental studies. In this study, we investigated the effects of pretreatment of a bolus dose of enteral glutamine on ALI induced by OA in rats. METHODS Twenty-eight adult female Sprague-Dawley rats weighing 240-300 g were divided into four groups, 7 in each. Group I and group II received normal saline for 30 days, group III and group IV received glutamine at a dose of 1 g/kg for 10 days by gavage, and in group II and group IV 100 mg/kg OA was administered i.v. Histopathological examination of the lung was performed with light and electron microscopy. Levels of protein carbonyl, malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase levels were measured in tissue samples. Levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and total tissue oxidant status and total tissue antioxidant status were measured in serum samples. RESULTS Light microscopy showed that the total lung injury score of group IV was significantly lower than group II. Change in thickness of the fused basal lamina was not significantly different in groups II and IV under electron microscopy. TNF-α, IL-6, and IL-10 serum levels were higher in group II when compared to group I and significantly attenuated in group IV. CONCLUSION Pretreatment with a bolus dose of enteral glutamine minimized the extent of ALI induced by OA in rats.
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Affiliation(s)
- A Ebru Salman
- Anesthesiology and Reanimation Department, Atatürk Research and Training Hospital, Ankara, Turkey
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Abstract
Intestinal adaptation is a natural compensatory process that occurs following extensive intestinal resection, whereby structural and functional changes in the intestine improve nutrient and fluid absorption in the remnant bowel. In animal studies, postresection structural adaptations include bowel lengthening and thickening and increases in villus height and crypt depth. Functional changes include increased nutrient transporter expression, accelerated crypt cell differentiation, and slowed transit time. In adult humans, data regarding adaptive changes are sparse, and the mechanisms underlying intestinal adaptation remain to be fully elucidated. Several factors influence the degree of intestinal adaptation that occurs post resection, including site and extent of resection, luminal stimulation with enteral nutrients, and intestinotrophic factors. Two intestinotrophic growth factors, the glucagon-like peptide 2 analog teduglutide and recombinant growth hormone (somatropin), are now approved for clinical use in patients with short bowel syndrome (SBS). Both agents enhance fluid absorption and decrease requirements for parenteral nutrition (PN) and/or intravenous fluid. Intestinal adaptation has been thought to be limited to the first 1-2 years following resection in humans. However, recent data suggest that a significant proportion of adult patients with SBS can achieve enteral autonomy, even after many years of PN dependence, particularly with trophic stimulation.
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Affiliation(s)
- Kelly A Tappenden
- Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, Illinois
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Takechi H, Mawatari K, Harada N, Nakaya Y, Asakura M, Aihara M, Takizawa H, Goto M, Nishino T, Minato T, Furukita Y, Yamamoto Y, Yuasa Y, Yamai H, Yoshida T, Seike J, Tangoku A. Glutamine protects the small intestinal mucosa in anticancer drug-induced rat enteritis model. THE JOURNAL OF MEDICAL INVESTIGATION 2014; 61:59-64. [DOI: 10.2152/jmi.61.59] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Affiliation(s)
- Hirokazu Takechi
- Department of Thoracic, Endocrine Surgery and Oncology, Institute of Health Biosciences, the University of Tokushima Graduate School
| | - Kazuaki Mawatari
- Department of Preventive Environent and Nutrition, Institute of Health Biosciences, the University of Tokushima Graduate School
| | - Nagakatsu Harada
- Department of Nutrition and Metabolism, Institute of Health Biosciences, the University of Tokushima Graduate School
| | - Yutaka Nakaya
- Department of Nutrition and Metabolism, Institute of Health Biosciences, the University of Tokushima Graduate School
| | - Megumi Asakura
- Department of Nutrition and Metabolism, Institute of Health Biosciences, the University of Tokushima Graduate School
| | - Mutsumi Aihara
- Department of Preventive Environent and Nutrition, Institute of Health Biosciences, the University of Tokushima Graduate School
| | - Hiromitsu Takizawa
- Department of Thoracic, Endocrine Surgery and Oncology, Institute of Health Biosciences, the University of Tokushima Graduate School
| | - Masakazu Goto
- Department of Thoracic, Endocrine Surgery and Oncology, Institute of Health Biosciences, the University of Tokushima Graduate School
| | - Takeshi Nishino
- Department of Thoracic, Endocrine Surgery and Oncology, Institute of Health Biosciences, the University of Tokushima Graduate School
| | - Takuya Minato
- Department of Thoracic, Endocrine Surgery and Oncology, Institute of Health Biosciences, the University of Tokushima Graduate School
| | - Yoshihito Furukita
- Department of Thoracic, Endocrine Surgery and Oncology, Institute of Health Biosciences, the University of Tokushima Graduate School
| | - Yota Yamamoto
- Department of Thoracic, Endocrine Surgery and Oncology, Institute of Health Biosciences, the University of Tokushima Graduate School
| | - Yasuhiro Yuasa
- Department of Thoracic, Endocrine Surgery and Oncology, Institute of Health Biosciences, the University of Tokushima Graduate School
| | - Hiromichi Yamai
- Department of Thoracic, Endocrine Surgery and Oncology, Institute of Health Biosciences, the University of Tokushima Graduate School
| | - Takahiro Yoshida
- Department of Thoracic, Endocrine Surgery and Oncology, Institute of Health Biosciences, the University of Tokushima Graduate School
| | - Junichi Seike
- Department of Thoracic, Endocrine Surgery and Oncology, Institute of Health Biosciences, the University of Tokushima Graduate School
| | - Akira Tangoku
- Department of Thoracic, Endocrine Surgery and Oncology, Institute of Health Biosciences, the University of Tokushima Graduate School
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Corbee RJ, Kerkhoven WJSV. Nutritional Support of Dogs and Cats after Surgery or Illness. ACTA ACUST UNITED AC 2014. [DOI: 10.4236/ojvm.2014.44006] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Ruth MR, Field CJ. The immune modifying effects of amino acids on gut-associated lymphoid tissue. J Anim Sci Biotechnol 2013; 4:27. [PMID: 23899038 PMCID: PMC3750756 DOI: 10.1186/2049-1891-4-27] [Citation(s) in RCA: 129] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2013] [Accepted: 07/29/2013] [Indexed: 12/11/2022] Open
Abstract
The intestine and the gut-associated lymphoid tissue (GALT) are essential components of whole body immune defense, protecting the body from foreign antigens and pathogens, while allowing tolerance to commensal bacteria and dietary antigens. The requirement for protein to support the immune system is well established. Less is known regarding the immune modifying properties of individual amino acids, particularly on the GALT. Both oral and parenteral feeding studies have established convincing evidence that not only the total protein intake, but the availability of specific dietary amino acids (in particular glutamine, glutamate, and arginine, and perhaps methionine, cysteine and threonine) are essential to optimizing the immune functions of the intestine and the proximal resident immune cells. These amino acids each have unique properties that include, maintaining the integrity, growth and function of the intestine, as well as normalizing inflammatory cytokine secretion and improving T-lymphocyte numbers, specific T cell functions, and the secretion of IgA by lamina propria cells. Our understanding of this area has come from studies that have supplemented single amino acids to a mixed protein diet and measuring the effect on specific immune parameters. Future studies should be designed using amino acid mixtures that target a number of specific functions of GALT in order to optimize immune function in domestic animals and humans during critical periods of development and various disease states.
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Affiliation(s)
- Megan R Ruth
- Department of Agricultural, Food and Nutritional Science, 4-126A Li Ka Shing Health Research Innovation Centre, University of Alberta, Edmonton, AB T6G 2E1, Canada.
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Aydoğmuş MT, Tomak Y, Tekin M, Katı I, Hüseyinoğlu U. Glutamine supplemented parenteral nutrition to prevent ventilator-associated pneumonia in the intensive care unit. Balkan Med J 2012; 29:414-8. [PMID: 25207045 DOI: 10.5152/balkanmedj.2012.043] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2012] [Accepted: 05/30/2012] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVE Ventilator-associated pneumonia (VAP) is a form of nosocomial pneumonia that increases patient morbidity and mortality, length of hospital stay, and healthcare costs. Glutamine preserves the intestinal mucosal structure, increases immune function, and reduces harmful changes in gut permeability in patients receiving total parenteral nutrition (TPN). We hypothesized that TPN supplemented by glutamine might prevent the development of VAP in patients on mechanical ventilator support in the intensive care unit (ICU). MATERIAL AND METHODS With the approval of the ethics committee and informed consent from relatives, 60 patients who were followed in the ICU with mechanical ventilator support were included in our study. Patients were divided into three groups. The first group received enteral nutrition (n=20), and the second was prescribed TPN (n=20) while the third group was given glutamine-supplemented TPN (n=20). C-reactive protein (CRP), sedimentation rate, body temperature, development of purulent secretions, increase in the amount of secretions, changes in the characteristics of secretions and an increase in requirement of deep tracheal aspiration were monitored for seven days by daily examination and radiographs. RESULTS No statistically significant difference was found among groups in terms of development of VAP (p=0.622). CONCLUSION Although VAP developed at a lower rate in the glutamine-supplemented TPN group, no statistically significant difference was found among any of the groups. Glutamine-supplemented TPN may have no superiority over unsupplemented enteral and TPN in preventing VAP.
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Affiliation(s)
- Meltem Türkay Aydoğmuş
- Department of Anesthesiology and Reanimation, Faculty of Medicine, Yüzüncü Yıl University, Van, Turkey
| | - Yakup Tomak
- Department of Anesthesiology and Reanimation, Faculty of Medicine, Rize University, Rize, Turkey
| | - Murat Tekin
- Department of Anesthesiology and Reanimation, Faculty of Medicine, Yüzüncü Yıl University, Van, Turkey
| | - Ismail Katı
- Department of Anesthesiology and Reanimation, Faculty of Medicine, Yüzüncü Yıl University, Van, Turkey
| | - Urfettin Hüseyinoğlu
- Department of Anesthesiology and Reanimation, Faculty of Medicine, Yüzüncü Yıl University, Van, Turkey
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Gardiner KR, Kirk SJ, Rowlands BJ. Novel substrates to maintain gut integrity. Nutr Res Rev 2012; 8:43-66. [PMID: 19094279 DOI: 10.1079/nrr19950006] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- K R Gardiner
- Department of Surgery, The Queen's University of Belfast, Institute of Clinical Science, Grosvenor Road, Belfast BT12 6BJ, Northern Ireland, UK
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20
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Atiomo W, Daykin CA. Metabolomic biomarkers in women with polycystic ovary syndrome: a pilot study. Mol Hum Reprod 2012; 18:546-53. [DOI: 10.1093/molehr/gas029] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
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Moe-Byrne T, Wagner JVE, McGuire W. Glutamine supplementation to prevent morbidity and mortality in preterm infants. Cochrane Database Syst Rev 2012:CD001457. [PMID: 22419279 DOI: 10.1002/14651858.cd001457.pub4] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
BACKGROUND 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. OBJECTIVES To determine the effects of glutamine supplementation on mortality and morbidity in preterm infants. SEARCH METHODS We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (The Cochrane Library, 2011, Issue 4), MEDLINE, EMBASE and CINAHL (to November 2011), conference proceedings and previous reviews. SELECTION CRITERIA 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. DATA COLLECTION AND ANALYSIS 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. MAIN RESULTS We identified 11 randomised controlled trials in which a total of 2771 preterm infants participated. Five trials assessed enteral glutamine supplementation and six trials assessed parenteral glutamine supplementation. The trials were generally of good methodological quality. Meta-analysis did not detect a statistically significant effect of glutamine supplementation on mortality [typical relative risk 0.98 (95% confidence interval 0.80 to 1.18); 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. Two trials that assessed neurodevelopmental outcomes at 18 to 24 months did not find any statistically significant differences in various assessments. AUTHORS' CONCLUSIONS The available trial data do not provide evidence that glutamine supplementation confers important benefits for preterm infants.
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Tazuke Y, Maeda K, Wasa M, Satoko N, Fukuzawa M. Protective mechanism of glutamine on the expression of proliferating cell nuclear antigen after cisplatin-induced intestinal mucosal injury. Pediatr Surg Int 2011; 27:151-8. [PMID: 21080177 DOI: 10.1007/s00383-010-2798-8] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
BACKGROUND Glutamine prevents the intestinal mucosal injury induced by chemotherapy. However, the mechanism has not yet been elucidated. Proliferating cell nuclear antigen (PCNA) is expressed in the nuclei of cells during the DNA synthesis phase of the cell cycle, and PCNA is also involved in the DNA damage tolerance pathway known as post-replication repair. We hypothesized that glutamine supplementation might stimulate the intestinal epithelial cell cycle interruption induced by chemotherapy. The effect of supplemental glutamine after cisplatin-induced intestinal mucosal injury on the expression of PCNA was investigated. MATERIALS AND METHODS The male Wister rats were divided into three groups; a control group (control n = 5), which received standard rat diet; the Cis group (cisplatin 6 mg/kg i.p., n = 5), and the Cis + Gln group [cisplatin + Ala-Glutamine (0.5 g/day × 3 days p.o., n = 5)]. After 1, 3, and 7 days of chemotherapy, PCNA, and glutamine transporter (ASCT2) expression in the small intestine (jejunum and ileum) was investigated. RESULTS The expression of PCNA in the crypt of the small intestine (jejunum and ileum) decreased after chemotherapy, while the expression strongly increased by glutamine administration, even if it was after chemotherapy. On day 1, both the mRNA expression of the glutamine transporter (ASCT2) and PCNA expression in crypt cells were significantly increased by administration of glutamine (Cis + Gln group). The increased expression of ACST2 appeared earlier than in the Cis group. In the Cis + Gln group, the PCNA expression was normalized on day 3, and the expression was same as that in the control group on day 3. CONCLUSION Glutamine supplementation rapidly improved the expression of PCNA after cisplatin-induced intestinal mucosal injury. The effects of glutamine may be due to an anti-oxidant effect, but the amino acid might also attenuate the initial mucosal injury and improve intestinal cell turnover.
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Affiliation(s)
- Yuko Tazuke
- Department of Pediatric Surgery, Jichi Children's Medical Center Tochigi/Jichi Medical University, Tochigi, Japan.
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Wolff BS, Meirelles K, Meng Q, Pan M, Cooney RN. Roux-en-Y gastric bypass alters small intestine glutamine transport in the obese Zucker rat. Am J Physiol Gastrointest Liver Physiol 2009; 297:G594-601. [PMID: 19556357 PMCID: PMC2739821 DOI: 10.1152/ajpgi.00104.2009] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The metabolic effects of Roux-en-Y gastric bypass (RYGB) are caused by postsurgical changes in gastrointestinal anatomy affecting gut function. Glutamine is a critical gut nutrient implicated in regulating glucose metabolism as a substrate for intestinal gluconeogenesis. The present study examines the effects of obesity and RYGB on intestinal glutamine transport and metabolism. First, lean and obese Zucker rats (ZRs) were compared. Then the effects of RYGB and sham surgery with pair feeding (PF) in obese ZRs were studied. Segments of small intestine (biliopancreatic limb, Roux limb, and common channel) mucosa were harvested and brush border membrane vesicles (BBMVs) were isolated on postoperative day 28. Glutamine transporter activity and abundance, B(0)AT1 protein, and mRNA levels were measured. Levels of glutaminase, cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C), and glucose-6-phosphatase (G6Pase) were measured to assess glutamine metabolism and intestinal gluconeogenesis. Obesity increased glutamine transport and B(0)AT1 expression throughout the intestine. RYGB increased glutamine transport activity in the biliopancreatic (3.8-fold) and Roux limbs (1.4-fold) but had no effect on the common channel. The relative abundance of B(0)AT1 mRNA and protein were increased in the biliopancreatic (6-fold) and Roux limbs (10-fold) after RYGB (P < 0.05 vs. PF), but not the common channel. Glutaminase levels were increased, whereas the relative abundance of PEPCK-C and G6Pase were decreased in all segments of intestine after RYGB. RYGB selectively increased glutamine absorption in biliopancreatic and Roux limbs by a mechanism involving increased B(0)AT1 expression. Post-RYGB glutaminase levels were increased, but the reductions in PEPCK-C and G6Pase suggest that RYGB downregulates intestinal gluconeogenesis.
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Affiliation(s)
- Brynn S. Wolff
- Department of Surgery and Department of Cellular and Molecular Physiology, Penn State Milton S. Hershey Medical Center, Pennsylvania State College of Medicine, Hershey, Pennsylvania
| | - Katia Meirelles
- Department of Surgery and Department of Cellular and Molecular Physiology, Penn State Milton S. Hershey Medical Center, Pennsylvania State College of Medicine, Hershey, Pennsylvania
| | - Qinghe Meng
- Department of Surgery and Department of Cellular and Molecular Physiology, Penn State Milton S. Hershey Medical Center, Pennsylvania State College of Medicine, Hershey, Pennsylvania
| | - Ming Pan
- Department of Surgery and Department of Cellular and Molecular Physiology, Penn State Milton S. Hershey Medical Center, Pennsylvania State College of Medicine, Hershey, Pennsylvania
| | - Robert N. Cooney
- Department of Surgery and Department of Cellular and Molecular Physiology, Penn State Milton S. Hershey Medical Center, Pennsylvania State College of Medicine, Hershey, Pennsylvania
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Klaus JA, Rudloff E, Kirby R. Nasogastric tube feeding in cats with suspected acute pancreatitis: 55 cases (2001-2006). J Vet Emerg Crit Care (San Antonio) 2009; 19:337-46. [DOI: 10.1111/j.1476-4431.2009.00438.x] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Glutamine decreases the duration of postoperative ileus after abdominal surgery: an experimental study of conscious dogs. Dig Dis Sci 2009; 54:1208-13. [PMID: 18754091 DOI: 10.1007/s10620-008-0478-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2008] [Accepted: 07/24/2008] [Indexed: 12/09/2022]
Abstract
Postoperative ileus (POI) is a transient bowel dysmotility that occurs following many types of operations and is one of the most common complications of gastrointestinal surgery. We hypothesized that enteral supplementation of glutamine after abdominal surgery would restore fuel to the small intestine, suppress oxidative stress, and lead to improvement in POI. Twelve dogs underwent distal gastrectomy and were each randomly assigned to one of two groups based on postoperative treatment: the water injection (control) group and the glutamine injection group. Water (40 ml) or L(+)-glutamine (1 g/40 ml water) was injected into the residual stomach through the gastric tube every 12 h after surgery for 7 days. Changes in the plasma and intestinal intracellular concentration of glutamine and in gastrointestinal motility were measured. The plasma and intracellular glutamine levels decreased after the operation in both groups, although the decreased intracellular glutamine levels were not significantly different than preoperative levels. The glutamine group showed a significantly smaller decrease of the plasma glutamine level compared with the control group (P < 0.05). All the dogs showed gastrointestinal dysmotility after the operation. The mean length of time between the operation and the appearance of interdigestive migrating contractions in the glutamine group was significantly shorter than in the control group (22.4 +/- 3.1 h versus 37.8 +/- 4.0 h, respectively; P < 0.05). In conclusion, glutamine could act as a motility-recovery agent after abdominal surgery and thereby decrease the duration of POI.
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27
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Glutamine, arginine, and leucine signaling in the intestine. Amino Acids 2009; 37:111-22. [PMID: 19130170 DOI: 10.1007/s00726-008-0225-4] [Citation(s) in RCA: 231] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2008] [Accepted: 12/09/2008] [Indexed: 12/14/2022]
Abstract
Glutamine and leucine are abundant constituents of plant and animal proteins, whereas the content of arginine in foods and physiological fluids varies greatly. Besides their role in protein synthesis, these three amino acids individually activate signaling pathway to promote protein synthesis and possibly inhibit autophagy-mediated protein degradation in intestinal epithelial cells. In addition, glutamine and arginine stimulate the mitogen-activated protein kinase and mammalian target of rapamycin (mTOR)/p70 (s6) kinase pathways, respectively, to enhance mucosal cell migration and restitution. Moreover, through the nitric oxide-dependent cGMP signaling cascade, arginine regulates multiple physiological events in the intestine that are beneficial for cell homeostasis and survival. Available evidence from both in vitro and in vivo animal studies shows that glutamine and arginine promote cell proliferation and exert differential cytoprotective effects in response to nutrient deprivation, oxidative injury, stress, and immunological challenge. Additionally, when nitric oxide is available, leucine increases the migration of intestinal cells. Therefore, through cellular signaling mechanisms, arginine, glutamine, and leucine play crucial roles in intestinal growth, integrity, and function.
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Kerem M, Salman B, Pasaoglu H, Bedirli A, Alper M, Katircioglu H, Atici T, Perçin EF, Ofluoglu E. Effects of microalgae chlorella species crude extracts on intestinal adaptation in experimental short bowel syndrome. World J Gastroenterol 2008; 14:4512-7. [PMID: 18680231 PMCID: PMC2731278 DOI: 10.3748/wjg.14.4512] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the effects of chlorella crude extract (CCE) on intestinal adaptation in rats subjected to short bowel syndrome (SBS).
METHODS: Wistar rats weighing 230-260 g were used in the study. After anesthesia a 75% small bowel resection was performed. Rats were randomized and divided into groups. Control group (n = 10): where 5% dextrose was given through a gastrostomy tube, Enteral nutrition (EN) group (n = 10): Isocaloric and isonitrogen EN (Alitraq, Abbott, USA), study group (n = 10): CCE was administrated through a gastrostomy tube. Rats were sacrificed on the fifteenth postoperative day and blood and tissue samples were taken. Histopathologic evaluation, intestinal mucosal protein and DNA levels, intestinal proliferation and apoptosis were determined in intestinal tissues, and total protein, albumin and citrulline levels in blood were studied.
RESULTS: In rats receiving CCE, villus lengthening, crypt depth, mucosal DNA and protein levels, intestinal proliferation, and serum citrulline, protein and albumin levels were found to be significantly higher than those in control group. Apoptosis in CCE treated rats was significantly reduced when compared to EN group rats.
CONCLUSION: CCE has beneficial effects on intestinal adaptation in experimental SBS.
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29
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Marik PE, Zaloga GP. Immunonutrition in critically ill patients: a systematic review and analysis of the literature. Intensive Care Med 2008. [PMID: 18626628 DOI: 10.1007/s00134-008-1213-1216] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
BACKGROUND The role of immuno-modulating diets (IMDs) in critically ill patients is controversial. OBJECTIVE The goal of this meta-analysis was to determine the impact of IMD's on hospital mortality, nosocomial infections and length of stay (LOS) in critically ill patients. Outcome was stratified according to type of IMD and patient setting. DATA SOURCES MEDLINE, Embase, Cochrane Register of Controlled Trials. STUDY SELECTION RCT's that compared the outcome of critically ill patients randomized to an IMD or a control diet. DATA SYNTHESIS Twenty-four studies (with a total of 3013 patients) were included in the meta-analysis; 12 studies included ICU patients, 5 burn patients and 7 trauma patients. Four of the studies used formulas supplemented with arginine, two with arginine and glutamine, nine with arginine and fish oil (FO), two with arginine, glutamine and FO, six with glutamine alone and three studies used a formula supplemented with FO alone. Overall IMD's had no effect on mortality or LOS, but reduced the number of infections (OR 0.63; 95% CI 0.47-0.86, P = 0.004, I(2) = 49%). Mortality, infections and LOS were significantly lower only in the ICU patients receiving the FO IMD (OR 0.42, 95% CI 0.26-0.68; OR 0.45, 95% CI 0.25-0.79 and WMD -6.28 days, 95% CI -9.92 to -2.64, respectively). CONCLUSIONS An IMD supplemented with FO improved the outcome of medical ICU patients (with SIRS/sepsis/ARDS). IMDs supplemented with arginine with/without additional glutamine or FO do not appear to offer an advantage over standard enteral formulas in ICU, trauma and burn patients.
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Affiliation(s)
- Paul E Marik
- Division of Pulmonary and Critical Care Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.
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Marik PE, Zaloga GP. Immunonutrition in critically ill patients: a systematic review and analysis of the literature. Intensive Care Med 2008; 34:1980-90. [PMID: 18626628 DOI: 10.1007/s00134-008-1213-6] [Citation(s) in RCA: 217] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2008] [Accepted: 06/22/2008] [Indexed: 12/26/2022]
Abstract
BACKGROUND The role of immuno-modulating diets (IMDs) in critically ill patients is controversial. OBJECTIVE The goal of this meta-analysis was to determine the impact of IMD's on hospital mortality, nosocomial infections and length of stay (LOS) in critically ill patients. Outcome was stratified according to type of IMD and patient setting. DATA SOURCES MEDLINE, Embase, Cochrane Register of Controlled Trials. STUDY SELECTION RCT's that compared the outcome of critically ill patients randomized to an IMD or a control diet. DATA SYNTHESIS Twenty-four studies (with a total of 3013 patients) were included in the meta-analysis; 12 studies included ICU patients, 5 burn patients and 7 trauma patients. Four of the studies used formulas supplemented with arginine, two with arginine and glutamine, nine with arginine and fish oil (FO), two with arginine, glutamine and FO, six with glutamine alone and three studies used a formula supplemented with FO alone. Overall IMD's had no effect on mortality or LOS, but reduced the number of infections (OR 0.63; 95% CI 0.47-0.86, P = 0.004, I(2) = 49%). Mortality, infections and LOS were significantly lower only in the ICU patients receiving the FO IMD (OR 0.42, 95% CI 0.26-0.68; OR 0.45, 95% CI 0.25-0.79 and WMD -6.28 days, 95% CI -9.92 to -2.64, respectively). CONCLUSIONS An IMD supplemented with FO improved the outcome of medical ICU patients (with SIRS/sepsis/ARDS). IMDs supplemented with arginine with/without additional glutamine or FO do not appear to offer an advantage over standard enteral formulas in ICU, trauma and burn patients.
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Affiliation(s)
- Paul E Marik
- Division of Pulmonary and Critical Care Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.
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Tubman TRJ, Thompson SW, McGuire W. Glutamine supplementation to prevent morbidity and mortality in preterm infants. Cochrane Database Syst Rev 2008:CD001457. [PMID: 18253992 DOI: 10.1002/14651858.cd001457.pub3] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
BACKGROUND Glutamine endogenous biosynthesis may be insufficient for tissue needs in states of metabolic stress. Trials in adults have suggested that glutamine supplementation improves clinical outcomes in critically ill adults. It has been suggested that glutamine supplementation may benefit preterm infants, particularly very low birth weight infants. OBJECTIVES To determine the effects of glutamine supplementation on mortality and morbidity in preterm infants. SEARCH STRATEGY The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2007), MEDLINE (1966 - July 2007), EMBASE (1980 - July 2007), conference proceedings, and previous reviews. SELECTION CRITERIA 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. DATA COLLECTION AND ANALYSIS The standard methods of the Cochrane Neonatal Review Group were used, with separate evaluation of trial quality and data extraction by two authors. Data were synthesised using a fixed effects model and reported using typical relative risk, typical risk difference and weighted mean difference. MAIN RESULTS 2365 preterm infants have participated in seven randomised controlled trials. All of the participating infants were of very low birth weight. Three trials assessed enteral glutamine supplementation and four trials assessed parenteral glutamine supplementation. The trials were generally of good methodological quality with adequate allocation concealment, blinding of caregivers and assessors to the intervention, and complete or near-complete follow-up of recruited infants. Glutamine supplementation does not have a statistically significant effect on mortality: typical relative risk 0.98 (95% confidence interval 0.80 to 1.20); typical risk difference 0.00 (95% confidence interval -0.03 to 0.02). The only trial that assessed long-term outcomes did not find any statistically significant differences in various assessments of neurodevelopment at 18 months corrected age. Glutamine supplementation does not have a statistically significant effect on other neonatal morbidities including invasive infection, necrotising enterocolitis, time to achieve full enteral nutrition, or duration of hospital stay. AUTHORS' CONCLUSIONS The available data from good quality randomised controlled trials indicate that glutamine supplementation does not confer benefits for preterm infants. The narrow confidence intervals for the effect size estimates suggest that a further trial of this intervention is not a research priority.
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Affiliation(s)
- T R J Tubman
- Royal Maternity Hospital, Neonatal Intensive Care Unit, Grosvenor Road, Belfast, Northern Ireland, UK.
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Fan BG. Effects of Parenteral Nutrition on the Exocrine Pancreas in Response to Cholecystokinin. JPEN J Parenter Enteral Nutr 2008; 32:57-62. [PMID: 18165448 DOI: 10.1177/014860710803200157] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Affiliation(s)
- Bo-Guang Fan
- From the Centre for Gastrointestinal Disease, Taizhou Hospital, Zhejiang, China
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Vissers YLJ, Debats IBJG, Luiking YC, Jalan R, van der Hulst RRWJ, Dejong CHC, Deutz NEP. Pros and cons of L-arginine supplementation in disease. Nutr Res Rev 2007; 17:193-210. [DOI: 10.1079/nrr200490] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The amino acid arginine and one of its metabolites NO have gathered broad attention in the last decade. Although arginine is regarded as a conditionally essential amino acid in disease, L-arginine supplementation in severe illness has not found its way into clinical practice. This might be due to the invalid interpretation of results from studies with immune-enhancing diets containing L-arginine amongst other pharmaconutrients. However, not much attention is given to research using L-arginine as a monotherapy and the possibility of the alternative hypothesis: that L-arginine supplementation is beneficial in disease. The present review will discuss data from studies in healthy and diseased animals and patients with monotherapy of L-arginine to come to an objective overview of positive and negative aspects of L-arginine supplementation in disease with special emphasis on sepsis, cancer, liver failure and wound healing.
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Williams EA, Elia M, Lunn PG. A double-blind, placebo-controlled, glutamine-supplementation trial in growth-faltering Gambian infants. Am J Clin Nutr 2007; 86:421-7. [PMID: 17684214 DOI: 10.1093/ajcn/86.2.421] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Growth faltering during infancy is a characteristic of life in developing countries. Previous studies have shown that small-intestine mucosal enteropathy, accompanied by endotoxemia and a persistent systemic inflammatory response, accounts for up to 64% of the growth faltering in Gambian infants. OBJECTIVE The objective was to test whether glutamine, with its putative trophic effects on enterocytes, immune cells, and intestinal integrity, can accelerate the repair of the intestine, lower immunostimulation, and reduce growth faltering. DESIGN Ninety-three infants aged 4-10 mo from the West Kiang region of The Gambia were studied in a double-blind, double-placebo, controlled trial. Glutamine (0.25 mg/kg body wt) or a placebo that contained an isonitrogenous, isoenergetic mix of nonessential amino acids was orally administered twice daily throughout the 5-mo rainy season. Anthropometric measurements were made monthly during the supplementation period and for 6 mo after supplementation. Intestinal permeability was measured monthly (by determining the ratio of lactulose to mannitol), and finger-prick blood samples were collected for the analysis of plasma proteins on 3 occasions. RESULTS Gambian infants showed a seasonal deterioration in growth and persistently elevated acute phase protein concentrations and intestinal permeability. Oral supplementation with glutamine did not improve growth (x +/- SE: weight gain, 60 +/- 19 and 69 +/- 20 g/mo; length gain, 1.01 +/- 0.05 and 0.95 +/- 0.03 cm/mo) or intestinal permeability [lactulose:mannitol ratio: 0.29 (95% CI: 0.23, 0.35) and 0.26 (95% CI: 0.21, 0.32)] in the glutamine and placebo groups, respectively. It also had no effect on infant morbidity or on plasma concentrations of immunoglobulins or acute phase proteins. CONCLUSION Glutamine supplementation failed to improve growth or intestinal status in malnourished Gambian infants.
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Affiliation(s)
- Elizabeth A Williams
- Human Nutrition Unit, University of Sheffield, Royal Hallamshire Hospital, Sheffield, United Kingdom
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Jonasson R, Essén-Gustavsson B, Jensen-Waern M. Blood concentrations of amino acids, glucose and lactate during experimental swine dysentery. Res Vet Sci 2007; 82:323-31. [PMID: 17078986 DOI: 10.1016/j.rvsc.2006.08.005] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2006] [Revised: 08/16/2006] [Accepted: 08/18/2006] [Indexed: 11/20/2022]
Abstract
The aim of this study was to examine blood concentrations of amino acids, glucose and lactate in association with experimental swine dysentery. Ten pigs (approximately 23kg) were orally inoculated with Brachyspira hyodysenteriae. Eight animals developed muco-haemorrhagic diarrhoea with impaired general appearance, changes in white blood cell counts and increased levels of the acute phase protein Serum Amyolid A. Blood samples were taken before inoculation, during the incubation period, during clinical signs of dysentery and during recovery. Neither plasma glucose nor lactate concentrations changed during the course of swine dysentery, but the serum concentrations of gluconeogenic non-essential amino acids decreased during dysentery. This was mainly due to decreases in alanine, glutamine, serine and tyrosine. Lysine increased during dysentery and at the beginning of the recovery period, and leucine increased during recovery. Glutamine, alanine and tyrosine levels show negative correlations with the numbers of neutrophils and monocytes. In conclusion, swine dysentery altered the blood concentrations of amino acids, but not of glucose or lactate.
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Affiliation(s)
- R Jonasson
- Department of Clinical Sciences, Section for Comparative Physiology and Medicine, Swedish University of Agricultural Sciences, P.O. Box 7018, S-750 07 Uppsala, Sweden.
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Abstract
Glutamine is a non-essential amino acid that can be synthesized de novo from glutamate. This synthesis can be increased by intravenous infusion of carbon precursors (alpha-ketoglutarate or amino acids) in adults and in infants. The metabolism of glutamine is highly compartmentalized between the splanchnic tissues and the periphery, so that orally administered glutamine is completely metabolized in the splanchnic compartment. Data from studies in adults and children show that plasma levels of glutamine decline during acute stress and illness. Because of its importance in several physiological functions (the demonstrated benefits of supplemental glutamine in adult burns and trauma patients and the inhibitory effect on proteolysis in the skeletal muscle in vitro), it has been suggested that during 'acute stress' the demands of glutamine outweigh its de novo synthesis, resulting in a fall in plasma glutamine levels. As a consequence, glutamine has been considered a 'conditionally essential' amino acid. Because of its instability in solution, glutamine is not routinely added to the parenteral amino acid mixtures. A number of clinical trials of parenteral and enteral supplementation of glutamine have been performed. The outcome measures examined have varied between acute effects and long-term complex clinical events such as mortality and risk of infections. Although acute studies in LBW babies have shown some beneficial effects such as changes in protein metabolism and activation of immune system, these have not been translated into prolonged advantages such as reduction in mortality or in nosocomial infection. The reasons for these differences are discussed.
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Affiliation(s)
- Prabhu S Parimi
- Department of Pediatrics, Case Western Reserve University at MetroHealth Medical Center, 2500 MetroHealth Drive, Cleveland, OH 44109-1998, USA.
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van den Berg A, Fetter WPF, Westerbeek EAM, van der Vegt IM, van der Molen HRA, van Elburg RM. The effect of glutamine-enriched enteral nutrition on intestinal permeability in very-low-birth-weight infants: a randomized controlled trial. JPEN J Parenter Enteral Nutr 2006; 30:408-14. [PMID: 16931609 DOI: 10.1177/0148607106030005408] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Very-low-birth-weight (VLBW) infants are susceptible to glutamine depletion. Glutamine depletion has negative effects on intestinal integrity. The lower infection rate in VLBW infants receiving glutamine-enriched enteral nutrition may originate from improved intestinal integrity, as reflected by decreased intestinal permeability. The aim of our study was to investigate whether glutamine-enriched enteral nutrition in VLBW infants enhances the normal decrease in intestinal permeability, as measured by the sugar absorption test (SAT). METHODS In a double-blind, randomized, placebo-controlled trial, VLBW infants (gestational age <32 weeks or birth weight <1,500 g) received enteral glutamine supplementation (0.3 g/kg/d) or an isonitrogenous placebo supplementation (alanine) between days 3 and 30 of life. Intestinal permeability, determined from the urinary lactulose/mannitol (L/M) ratio after an oral dose of lactulose and mannitol, was assessed at 4 time points: before the start of the study, and at days 7, 14, and 30 of life. RESULTS At least 2 SATs were performed in 45/52 (86%) and 45/50 (90%) infants in the glutamine-supplemented and control groups, respectively. Baseline patient and nutrition characteristics were not different between the groups. There was no effect of glutamine-enriched enteral nutrition on the decrease of the L/M ratio between the start and end of the study (p = .78). In both treatment groups, median urinary lactulose concentrations decreased (p < .001), whereas median urinary mannitol concentrations increased (p = .003). CONCLUSIONS Glutamine-enriched enteral nutrition does not enhance the postnatal decrease in intestinal permeability in VLBW infants. Any beneficial effect of glutamine may involve other aspects of intestinal integrity; for example, modulation of the intestinal inflammatory response.
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Affiliation(s)
- Anemone van den Berg
- Department of Pediatrics, Division of Neonatology, VU University Medical Center, Amsterdam, The Netherlands.
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Steiger E, DiBaise JK, Messing B, Matarese LE, Blethen S. Indications and recommendations for the use of recombinant human growth hormone in adult short bowel syndrome patients dependent on parenteral nutrition. J Clin Gastroenterol 2006; 40 Suppl 2:S99-106. [PMID: 16770169 DOI: 10.1097/01.mcg.0000212680.52290.02] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Given the lack of published guidelines regarding the use of trophic factors to treat patients with short bowel syndrome (SBS), a group of experts in the field convened to discuss best-practice strategies. Trophic factors, such as recombinant human growth hormone (r-hGH) and glucagon-like peptide-2 (GLP-2), may enhance intestinal adaptation and decrease parenteral nutrition (PN) requirements; therefore, their utility in treating SBS patients was evaluated. Available clinical data on use of r-hGH therapy in SBS patients were discussed, as were the utility of r-hGH in the PN weaning process, the optimal timing of r-hGH therapy, and how to select appropriate patients for r-hGH therapy. In addition, contraindications and precautions as well as adverse effects of r-hGH treatment were discussed. The meeting culminated with the development of a treatment algorithm to summarize best-practice recommendations for the management of SBS in adult patients. This algorithm involves attempting to wean patients off PN without the use of trophic factors. If this is unsuccessful, it is recommended that patients be treated with an r-hGH regimen or participate in investigational studies using other trophic factors.
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Affiliation(s)
- Ezra Steiger
- Intestinal Rehabilitation Program, Nutrition Support and Vascular Access Department, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
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Déchelotte P, Hasselmann M, Cynober L, Allaouchiche B, Coëffier M, Hecketsweiler B, Merle V, Mazerolles M, Samba D, Guillou YM, Petit J, Mansoor O, Colas G, Cohendy R, Barnoud D, Czernichow P, Bleichner G. L-alanyl-L-glutamine dipeptide-supplemented total parenteral nutrition reduces infectious complications and glucose intolerance in critically ill patients: the French controlled, randomized, double-blind, multicenter study. Crit Care Med 2006; 34:598-604. [PMID: 16505644 DOI: 10.1097/01.ccm.0000201004.30750.d1] [Citation(s) in RCA: 195] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE Glutamine (Gln)-supplemented total parenteral nutrition (TPN) improves clinical outcome after planned surgery, but the benefits of Gln-TPN for critically ill (intensive care unit; ICU) patients are still debated. DESIGN Prospective, double-blind, controlled, randomized trial. SETTING ICUs in 16 hospitals in France. PATIENTS One-hundred fourteen ICU patients admitted for multiple trauma (38), complicated surgery (65), or pancreatitis (11). INTERVENTIONS Patients were randomized to receive isocaloric isonitrogenous TPN via a central venous catheter providing 37.5 kcal and 1.5 g amino acids.kg-1.day-1 supplemented with either L-alanyl-L-glutamine dipeptide (0.5 g.kg-1.day-1; Ala-Gln group, n=58) or L-alanine+L-proline (control group, n=56) over at least 5 days. MEASUREMENTS AND MAIN RESULTS Complicated clinical outcome was defined a priori by the occurrence of infectious complications (according to the criteria of the Centers for Disease Control and Prevention), wound complication, or death. The two groups were compared by chi-square test on an intention-to-treat basis. The two groups did not differ at inclusion for type and severity of injury (mean simplified acute physiology score II, 30 vs. 30.5; mean injury severity score, 44.9 vs. 42.3). Similar volumes of TPN were administered in both groups. Ala-Gln-supplemented TPN was associated with a lower incidence of complicated outcome (41% vs. 61%; p<.05), which was mainly due to a reduced infection rate per patient (mean, 0.45 vs. 0.71; p<.05) and incidence of pneumonia (10 vs. 19; p<.05). Early death rate during treatment and 6-month survival were not different. Hyperglycemia was less frequent (20 vs. 30 patients; p<.05) and there were fewer insulin-requiring patients (14 vs. 22; p<.05) in the Ala-Gln group. CONCLUSIONS TPN supplemented with Ala-Gln dipeptide in ICU patients is associated with a reduced rate of infectious complications and better metabolic tolerance.
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Targarona Modena J, Barreda Cevasco L, Arroyo Basto C, Orellana Vicuña A, Portanova Ramírez M. Total enteral nutrition as prophylactic therapy for pancreatic necrosis infection in severe acute pancreatitis. Pancreatology 2005; 6:58-64. [PMID: 16327282 DOI: 10.1159/000090024] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2004] [Accepted: 11/05/2004] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To evaluate the capacity of enteral nutrition, in comparison with the total parenteral nutrition (TPN) plus antibiotic therapy, for avoiding pancreatic necrosis infection in the severe acute pancreatitis. METHODS In the period between October 1998 and September 2003, 87 patients met the inclusion criteria and took part in this research. Within the first week from their admission, 43 patients received TPN and 44 patients received total enteral nutrition (TEN). An adequate prophylactic antibiotic therapy was used in both groups. The severity of the manifestations was similar for both groups having a tomographic 'severity index' of 8 and an entry C-reactive protein of 208 and 203 mg/l, respectively. RESULTS The group that received TPN suffered an organ failure in 79% of the cases, while the percentage showed by the group that received TEN was 31%; 88 and 25% of the patients in each group requiring a surgical intervention, respectively (p < 0.001). There was decreased presence of pancreatic necrosis infection in the group of patients that was supplied with TEN (20%) than in the group receiving TPN, where it reached 74% (p < 0.001). The death rate was significantly higher among the patients who received TPN, (35%), while for the patients who received TEN it was only 5% (p < 0.001). CONCLUSION TEN could be used as a prophylactic therapy for infected pancreatic necrosis since it significantly diminished the necrosis infection as well as the mortality.
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Affiliation(s)
- Javier Targarona Modena
- Department of General Surgery, Edgardo Rebagliati-Martins Hospital, Clinica Anglo Americana, Lima, Perú.
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Byrne TA, Wilmore DW, Iyer K, Dibaise J, Clancy K, Robinson MK, Chang P, Gertner JM, Lautz D. Growth hormone, glutamine, and an optimal diet reduces parenteral nutrition in patients with short bowel syndrome: a prospective, randomized, placebo-controlled, double-blind clinical trial. Ann Surg 2005; 242:655-61. [PMID: 16244538 PMCID: PMC1409868 DOI: 10.1097/01.sla.0000186479.53295.14] [Citation(s) in RCA: 125] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
OBJECTIVE To determine if growth hormone (GH) and glutamine (Gln) might allow for a reduction in parenteral nutrition (PN) in individuals with short bowel syndrome. BACKGROUND DATA Following massive intestinal resection, patients frequently sustain severe nutrient malabsorption and are dependent on PN for life. GH treatment with or without Gln might allow for a reduction in PN. METHODS A prospective, double-blind, randomized, placebo-controlled clinical trial performed in 41 adults dependent on PN. Following screening, patients were admitted to an in-house facility for 6 weeks. After 2 weeks of stabilization and dietary optimization, patients were randomized to one of 3 treatment arms (1:2:2 ratio): oral Gln (30 g/day) + GH placebo (control group, n = 9), Gln placebo + GH (0.1 mg/kg per day, n = 16), or Gln + GH (n = 16). Standard criteria based on clinical and laboratory measurements were followed to determine PN volume and content. After 4 weeks of treatment, patients were discharged and monitored; GH and GH placebo were discontinued, but the diet with Gln or Gln placebo was continued for 3 months. RESULTS Patients receiving GH + Gln placebo + diet showed greater reductions in PN volume (5.9 +/- 3.8 L/wk, mean +/- SD), PN calories (4338 +/- 1858 calories/wk), and PN infusions (3 +/- 2 infusions/wk) than corresponding reductions in the Gln + diet group (3.8 +/- 2.4 L/wk; 2633 +/- 1341 calories/wk; 2 +/- 1 infusions/wk, P < 0.05). Patients who received GH + Gln + diet showed the greatest reductions (7.7 +/- 3.2 L/wk; 5751 +/- 2082 calories/wk; 4 +/- 1 infusions/wk, P < 0.001 versus Gln + diet). At the 3-month follow-up, only patients who had received GH + Gln + diet maintained significant reductions in PN (P < 0.005) compared with the Gln + diet. CONCLUSIONS Treatment with GH + diet or GH + Gln + diet initially permitted significantly more weaning from PN than Gln + diet. Only subjects receiving GH + Gln + diet maintained this effect for at least 3 months.
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Affiliation(s)
- Theresa A Byrne
- Laboratory for Surgical Metabolism and Nutrition, Department of Surgery, Brigham and Woman's Hospital, Harvard Medical School, Boston, MA, USA
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Ropeleski MJ, Riehm J, Baer KA, Musch MW, Chang EB. Anti-apoptotic effects of L-glutamine-mediated transcriptional modulation of the heat shock protein 72 during heat shock. Gastroenterology 2005; 129:170-84. [PMID: 16012946 DOI: 10.1053/j.gastro.2005.05.017] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS During physiologic stress, L-glutamine becomes conditionally essential. Its deficiency results in altered epithelial barrier competence, bacterial translocation, and decreased survival. L-glutamine may attenuate these effects by modulating heat shock protein expression, a well-described effect in vitro. We sought to characterize L-glutamine-dependent transcriptional regulation in heat-shocked intestinal cells and to determine its physiologic relevance. METHODS IEC-18 and H4 intestinal cells were used. Heat shock protein 72 (Hsp72) gene expression was determined by Northern blotting and luciferase assays. Heat shock factor-1 (HSF-1) activation was assessed by electromobility shift assay, Western blotting, and HSF-1 minimal promoters. Phosphorylation and trimerization of HSF-1 were determined by immunoprecipitation and native nonreducing gradient polyacrylamide gel electrophoresis (PAGE). Camptothecin-induced apoptosis was monitored using caspase-3 and poly (ADP-ribose) polymerase [PARP]-specific antibodies and DNA Elisa +/- Hsp72 siRNA. RESULTS L-glutamine specifically augmented Hsp72 transcript abundance and HSF-1 DNA binding during heat shock. No glutamine-dependent differences in HSF-1 phosphorylation, trimerization, nuclear localization during heat shock, or HSF-1 minimal promoter activity were observed. Nevertheless, the presence of L-glutamine was an important determinant of wild-type Hsp72 promoter transcriptional activation. Reduced Hsp72 was associated with increased camptothecin-induced caspase-3 and PARP cleavage in glutamine-deficient cells. siRNA treated cells were less resistant to camptothecin. CONCLUSIONS Taken together, the data suggest that glutamine does not affect the classical pathway of HSF-1 activation and that glutamine-dependent upstream trans -factor binding elsewhere in the Hsp72 promoter or coactivator recruitment may determine Hsp72 abundance. L-glutamine potentiation of Hsp72 is associated with increased epithelial resistance to apoptotic injury.
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Affiliation(s)
- Mark J Ropeleski
- Gastrointestinal Diseases Research Unit, Department of Medicine, Queen's University, Kingston, Ontario, Canada
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van den Berg A, van Elburg RM, Teerlink T, Lafeber HN, Twisk JWR, Fetter WPF. A randomized controlled trial of enteral glutamine supplementation in very low birth weight infants: plasma amino acid concentrations. J Pediatr Gastroenterol Nutr 2005; 41:66-71. [PMID: 15990633 DOI: 10.1097/01.mpg.0000167497.55321.65] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVE Glutamine depletion has negative effects on the functional integrity of the gut and leads to immunosuppression. Very low birth weight (VLBW) infants are susceptible to glutamine depletion, as enteral nutrition is limited in the first weeks of life. Enteral glutamine supplementation may have a positive effect on feeding tolerance, infectious morbidity and short-term outcome. The aim of the study was to determine the effect of enteral glutamine supplementation on plasma amino acid concentrations, reflecting one aspect of safety of enteral glutamine supplementation in VLBW infants. METHODS In a double-blind placebo-controlled randomized controlled trial, VLBW infants (gestational age <32 weeks or birth weight <1500 g) received enteral glutamine supplementation (0.3 g/kg per day) or isonitrogenous placebo supplementation (alanine) between day 3 and day 30 of life. Supplementation was added to breast milk or to preterm formula. Plasma amino acid concentrations were measured at four time points: before the start of the study and at days 7, 14 and 30 of life. RESULTS Baseline patient and nutritional characteristics were not different in glutamine (n = 52) and control (n = 50) groups. Plasma concentrations of most essential and non-essential amino acids increased throughout the study period. There was no effect of enteral glutamine supplementation. In particular, the increase of plasma glutamine and glutamate concentrations was not different between the treatment groups (P = 0.49 and P = 0.34 respectively, day 30). CONCLUSIONS Enteral glutamine supplementation in VLBW infants does not alter plasma concentrations of glutamine, glutamate or other amino acids. Enteral supplementation in a dose of 0.3 g/kg per day seems safe in VLBW infants.
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Affiliation(s)
- Anemone van den Berg
- Department of Pediatrics, VU University Medical Center, Amsterdam, the Netherlands.
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van den Berg A, van Elburg RM, Westerbeek EAM, Twisk JWR, Fetter WPF. Glutamine-enriched enteral nutrition in very-low-birth-weight infants and effects on feeding tolerance and infectious morbidity: a randomized controlled trial. Am J Clin Nutr 2005; 81:1397-404. [PMID: 15941893 DOI: 10.1093/ajcn/81.6.1397] [Citation(s) in RCA: 74] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Glutamine depletion has negative effects on the functional integrity of the gut and leads to immunosuppression. Very-low-birth-weight (VLBW) infants are susceptible to glutamine depletion because nutrition is limited in the first weeks of life. OBJECTIVE The objective was to determine the effect of glutamine-enriched enteral nutrition on feeding tolerance, infectious morbidity, and short-term outcome in VLBW infants. DESIGN In a double-blind randomized controlled trial, VLBW infants (gestational age <32 wk or birth weight <1500 g) were allocated to receive enteral glutamine supplementation (0.3 g . kg(-1) . d(-1)) or isonitrogenous control supplementation (alanine) between days 3 and 30 of life. The supplementations were added to breast milk or to preterm formula. The primary endpoint for the study was time to full enteral feeding. Secondary endpoints were other variables of feeding tolerance, infectious morbidity, and short-term outcome. RESULTS Baseline patient and nutritional characteristics were not significantly different in the glutamine-supplemented (n = 52) and the control (n = 50) groups. The median time to full enteral feeding was 13 d (range: 7-31 d) in the glutamine-supplemented group and 13 d (range: 6-35 d) in the control group (hazard ratio: 1.19; 95% CI: 0.79, 1.79; P = 0.40). In the glutamine-supplemented group, 26 of 52 infants (50%) had >/=1 serious infection compared with 38 of 50 (76%) in the control group (odds ratio: 0.32; 95% CI: 0.14, 0.74; P = 0.008). Other variables of feeding tolerance and short-term outcome were not significantly different between groups. CONCLUSIONS Glutamine-enriched enteral nutrition did not improve feeding tolerance or short-term outcome in VLBW infants. However, infectious morbidity was significantly lowered in infants who received glutamine-enriched enteral nutrition.
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Affiliation(s)
- Anemone van den Berg
- Department of Pediatrics and the Institute of Research in Extramural Medicine, VU University Medical Center, Amsterdam, Netherlands.
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Duran B. The effects of long-term total parenteral nutrition on gut mucosal immunity in children with short bowel syndrome: a systematic review. BMC Nurs 2005; 4:2. [PMID: 15686591 PMCID: PMC549542 DOI: 10.1186/1472-6955-4-2] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2004] [Accepted: 02/01/2005] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND: Short bowel syndrome (SBS) is defined as the malabsorptive state that often follows massive resection of the small intestine. Most cases originate in the newborn period and result from congenital anomalies. It is associated with a high morbidity, is potentially lethal and often requires months, sometimes years, in the hospital and home on total parenteral nutrition (TPN). Long-term survival without parenteral nutrition depends upon establishing enteral nutrition and the process of intestinal adaptation through which the remaining small bowel gradually increases its absorptive capacity. The purpose of this article is to perform a descriptive systematic review of the published articles on the effects of TPN on the intestinal immune system investigating whether long-term TPN induces bacterial translocation, decreases secretory immunoglobulin A (S-IgA), impairs intestinal immunity, and changes mucosal architecture in children with SBS. METHODS: The databases of OVID, such as MEDLINE and CINAHL, Cochran Library, and Evidence-Based Medicine were searched for articles published from 1990 to 2001. Search terms were total parenteral nutrition, children, bacterial translocation, small bowel syndrome, short gut syndrome, intestinal immunity, gut permeability, sepsis, hyperglycemia, immunonutrition, glutamine, enteral tube feeding, and systematic reviews. The goal was to include all clinical studies conducted in children directly addressing the effects of TPN on gut immunity. RESULTS: A total of 13 studies were identified. These 13 studies included a total of 414 infants and children between the ages approximately 4 months to 17 years old, and 16 healthy adults as controls; and they varied in design and were conducted in several disciplines. The results were integrated into common themes. Five themes were identified: 1) sepsis, 2) impaired immune functions: In vitro studies, 3) mortality, 4) villous atrophy, 5) duration of dependency on TPN after bowel resection. CONCLUSION: Based on this exhaustive literature review, there is no direct evidence suggesting that TPN promotes bacterial overgrowth, impairs neutrophil functions, inhibits blood's bactericidal effect, causes villous atrophy, or causes to death in human model.The hypothesis relating negative effects of TPN on gut immunity remains attractive, but unproven. Enteral nutrition is cheaper, but no safer than TPN. Based on the current evidence, TPN seems to be safe and a life saving solution.
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Affiliation(s)
- Beyhan Duran
- School of Nursing, University of Connecticut, Storrs, Connecticut, USA.
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Tubman TRJ, Thompson SW, McGuire W. Glutamine supplementation to prevent morbidity and mortality in preterm infants. Cochrane Database Syst Rev 2005:CD001457. [PMID: 15674878 DOI: 10.1002/14651858.cd001457.pub2] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
BACKGROUND Glutamine endogenous biosynthesis may be insufficient for tissue needs in states of metabolic stress. Trials in adults have suggested that glutamine supplementation improves clinical outcomes in critically ill adults. It has been suggested that glutamine supplementation may benefit preterm infants, particularly very low birth weight infants. OBJECTIVES To determine the effects of glutamine supplementation on mortality and morbidity in preterm infants. SEARCH STRATEGY We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2004), MEDLINE (1966 - August 2004), EMBASE (1980 - August 2004), conference proceedings, and previous reviews. SELECTION CRITERIA Randomised or quasi-randomised controlled trials that compared glutamine supplementation versus no glutamine supplementation in preterm babies at any time from birth to discharge from hospital. DATA COLLECTION AND ANALYSIS We extracted the data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by two reviewers, and synthesis of data using relative risk, risk difference and weighted mean difference. MAIN RESULTS More than 2300 infants have participated in six randomised controlled trials. All of the participating infants were of very low birth weight. Three trials assessed enteral glutamine supplementation, and three trials assessed parenteral glutamine supplementation. These trials were generally of good methodological quality with adequate allocation concealment, blinding of care-givers and assessors to the intervention, and complete or near-complete follow-up of recruited infants. We found that glutamine supplementation does not have a statistically significant effect on mortality: typical relative risk 0.98 (95% confidence interval 0.80 to 1.21); typical risk difference 0.00 (95% confidence interval -0.03 to 0.03). One of the trials assessed longer term neurodevelopmental outcomes (Poindexter 2004). The investigators reported that they did not find any statistically significant differences in various assessments of neurodevelopment (including Bayley scales) on follow up at 18 months corrected age. We found that glutamine supplementation does not have a statistically significant effect on the incidence of systemic infection (typical relative risk 1.02 (95% confidence interval 0.92 to 1.13); typical risk difference 0.01 (95% confidence interval -0.03 to 0.05)), necrotising enterocolitis (typical relative risk 1.02 (95% confidence interval 0.79 to 1.33); typical risk difference 0.00 (95% confidence interval -0.02 to 0.03)), days to full enteral nutrition (weighted mean difference -1.1 days (95% confidence interval -3.4 to 1.2)), or duration of hospital stay (weighted mean difference 0.65 days (95% confidence interval -2.9 to 4.2)). AUTHORS' CONCLUSIONS The available data from good quality randomised controlled trials suggest that glutamine supplementation does not confer clinically significant benefits for preterm infants. The narrow confidence intervals for the effect size estimates suggest that a further trial of this intervention is not a research priority.
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Affiliation(s)
- T R J Tubman
- Neonatal Intensive Care Unit, Royal Maternity Hospital, Grosvenor Road, Belfast, Northern Ireland, UK.
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Thomas S, Prabhu R, Balasubramanian KA. Surgical manipulation of the intestine and distant organ damage—protection by oral glutamine supplementation. Surgery 2005; 137:48-55. [PMID: 15614281 DOI: 10.1016/j.surg.2004.04.038] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
BACKGROUND The intestine is increasingly recognized as a primary effector of distant organ damage, such as the lung, after any abdominal surgery. Earlier studies have shown that surgical manipulation of the intestine induces generation of reactive oxygen species in the intestine, resulting in mucosal and lung damage. Because glutamine is preferentially used by the small intestine as an energy source, this study examined the effect of glutamine and glutamic acid on intestinal and lung damage after surgical manipulation. METHODS Controls and rats were pretreated for 7 days with 2% glutamine or glutamic acid, or the isonitrogenous amino acids glycine or alanine in the diet and subjected to surgical manipulation of the intestine. The intestine and lung were assessed for damage, and protection offered by various amino acids was studied. RESULTS Surgical manipulation resulted in oxidative stress in the intestine as evidenced by increased xanthine oxidase activity and decreased antioxidant status. Enterocyte mitochondria were also functionally impaired with altered calcium flux, decreased respiratory control ratio, and increased swelling. Gut manipulation also resulted in neutrophil infiltration and oxidative stress in the lung as assessed by an increase in myeloperoxidase activity, lipid peroxidation, and antioxidant status. Glutamine or glutamic acid supplementation for 7 days before surgical manipulation showed a protective effect against the intestinal and lung damage. CONCLUSIONS This study suggests that preoperative enteral glutamine or glutamic acid supplementation attenuates intestinal and lung damage in rats during surgical manipulation and that this effect might offer protection from postsurgical complications.
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Affiliation(s)
- Simmy Thomas
- Department of Gastrointestinal Sciences, Wellcome Trust Research Laboratory, Christian Medical College, Ida Scudder Road, Vellore-632004, India
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48
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van den Berg A, van Elburg RM, Twisk JWR, Fetter WPF. Glutamine-enriched enteral nutrition in very low birth weight infants. Design of a double-blind randomised controlled trial [ISRCTN73254583]. BMC Pediatr 2004; 4:17. [PMID: 15341667 PMCID: PMC517718 DOI: 10.1186/1471-2431-4-17] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2004] [Accepted: 09/01/2004] [Indexed: 12/27/2022] Open
Abstract
Background Enteral feeding of very low birth weight (VLBW) infants is a challenge, since metabolic demands are high and administration of enteral nutrition is limited by immaturity of the gastrointestinal tract. The amino acid glutamine plays an important role in maintaining functional integrity of the gut. In addition, glutamine is utilised at a high rate by cells of the immune system. In critically ill patients, glutamine is considered a conditionally essential amino acid. VLBW infants may be especially susceptible to glutamine depletion as nutritional supply of glutamine is limited in the first weeks after birth. Glutamine depletion has negative effects on functional integrity of the gut and leads to immunosuppression. This double-blind randomised controlled trial is designed to investigate the effect of glutamine-enriched enteral nutrition on feeding tolerance, infectious morbidity and short-term outcome in VLBW infants. Furthermore, an attempt is made to elucidate the role of glutamine in postnatal adaptation of the gut and modulation of the immune response. Methods VLBW infants (gestational age <32 weeks and/or birth weight <1500 g) are randomly allocated to receive enteral glutamine supplementation (0.3 g/kg/day) or isonitrogenous placebo supplementation between day 3 and 30 of life. Primary outcome is time to full enteral feeding (defined as a feeding volume ≥ 120 mL/kg/day). Furthermore, incidence of serious infections and short-term outcome are evaluated. The effect of glutamine on postnatal adaptation of the gut is investigated by measuring intestinal permeability and determining faecal microflora. The role of glutamine in modulation of the immune response is investigated by determining plasma Th1/Th2 cytokine concentrations following in vitro whole blood stimulation.
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Affiliation(s)
- Anemone van den Berg
- Department of Paediatrics, Division of Neonatology, VU University Medical Center, Amsterdam, the Netherlands
| | - Ruurd M van Elburg
- Department of Paediatrics, Division of Neonatology, VU University Medical Center, Amsterdam, the Netherlands
| | - Jos WR Twisk
- Institute of Research in Extramural Medicine, VU University Medical Center, Amsterdam, the Netherlands
| | - Willem PF Fetter
- Department of Paediatrics, Division of Neonatology, VU University Medical Center, Amsterdam, the Netherlands
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Duggan C, Stark AR, Auestad N, Collier S, Fulhan J, Gura K, Utter S, Teixeira-Pinto A, Donovan K, Lund D. Glutamine supplementation in infants with gastrointestinal disease: A randomized, placebo-controlled pilot trial. Nutrition 2004; 20:752-6. [PMID: 15325681 DOI: 10.1016/j.nut.2004.05.013] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
OBJECTIVE Glutamine (Gln) is a non-essential amino acid that plays an important role in energy metabolism for gastrointestinal epithelia and other cells with rapid turnover. We evaluated the effects of enteral supplementation with Gln in infants undergoing surgery for congenital or acquired gastrointestinal disease. METHODS This was a randomized, double-masked, controlled clinical trial. RESULTS Twenty infants were randomly assigned to receive Gln (n = 9) or placebo amino acid (n = 11), with a goal of supplemental amino acid intake of 0.4 g.kg(-1).d(-1). Infants were weaned from parenteral nutrition, and enteral feeds were started according to a standardized feeding protocol. Median (interquartile range) durations of parenteral nutrition were 39 d (12 to 99) in the Gln group and 21 d (6 to 59) in the control group (P = 0.201). Median (interquartile range) durations needed to reach 80% of the US recommended dietary allowance for energy with enteral nutrition were 24 d (8 to 55) in the Gln group and 12.5 d (5 to 32) in the control group (P = 0.313). There were no differences in the occurrence of infections between groups. Among all infants enrolled, significant correlations were found between duration of parenteral nutrition and residual small bowel length, peak concentrations of direct bilirubin, and alanine aminotransferase. Peak direct bilirubin was associated with longer duration of parenteral nutrition, shorter gestation, older age before feeds were started, shorter bowel length, and larger amounts of parenteral energy and protein intake. CONCLUSIONS In this pilot trial, enteral Gln supplementation was well tolerated among infants with surgical gastrointestinal disease. There was no effect observed on the duration of parenteral nutrition, tolerance of enteral feeds, or intestinal absorptive or barrier function. Larger, multicenter trials in infants with surgical gastrointestinal disease are needed due to the variability in important outcome measurements.
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Yalçin SS, Yurdakök K, Tezcan I, Oner L. Effect of glutamine supplementation on diarrhea, interleukin-8 and secretory immunoglobulin A in children with acute diarrhea. J Pediatr Gastroenterol Nutr 2004; 38:494-501. [PMID: 15097437 DOI: 10.1097/00005176-200405000-00007] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVE Glutamine is an important fuel for rapidly dividing cells such as enterocytes and lymphocytes. Exogenous glutamine supplementation in catabolic states preserves intestinal mucosal structure and function, decreases bacterial translocation, and supports normal immunologic responses. This study was planned to assess the effect of glutamine supplementation on duration and severity of diarrhea and to assess its immunomodulatory effect by measuring serum interleukin-8 (IL-8) and salivary immunoglobulin A (sIgA) in children with acute diarrhea. METHODS In this placebo-controlled, double-blind and randomized trial, 6- to 24-month-old otherwise healthy children admitted to the Diarrheal Diseases Training and Treatment Center with acute diarrhea received either 0.3 g/kg/day of glutamine (n = 63) or placebo (n = 65) for 7 days. Serum IL-8 and sIgA levels were determined on admission and 7 days later. All cases were followed until the diarrheal episode ended. Anthropometric measurements and history of subsequent infectious diseases were monitored monthly for 3 months after treatment. RESULTS Mean duration of diarrhea in the glutamine treated group was significantly shorter than that of the placebo group (3.40 +/- 1.96 days, 4.57 +/- 2.48 days, respectively; P = 0.004). No differences in serum IL-8 and sIgA were found between groups on admission or 1 week later. During 3 month follow-up, mean weight gain and incidence of infectious diseases were similar in both groups. CONCLUSION Duration of diarrhea was shorter in children supplemented with glutamine. The beneficial impact of glutamine supplementation seems to be through effects on gastrointestinal mucosa rather than the host immune response.
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Affiliation(s)
- S Songül Yalçin
- Department of Pediatrics, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
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