title: Metabolic effects of enteral versus parenteral alanyl-glutamine dipeptide administration in critically ill patients receiving enteral feeding: a pilot study.
abstract: BACKGROUND
  Glutamine (Gln) may become conditionally indispensable during critical illness. The short-term metabolic effects of enteral versus parenteral Gln supplementation are unknown in this clinical setting.
  
  
  OBJECTIVE
  We studied metabolic effects of intravenous (i.v.) alanyl-Gln dipeptide (AG) supplementation and enteral (e.n.) AG supplementation on plasma Gln concentration, antioxidant status, plasma lymphocyte subset number, gut permeability and nitrogen balance in adult critically ill patients requiring tube feeding compared to a control group not receiving Gln supplementation.
  
  
  METHODS
  In a double-blind, pilot clinical trial, 44 medical and surgical ICU patients received identical Gln-free tube feedings 24 h/day and were randomized to either isonitrogenous control (n=15), e.n. AG (n=15) or i.v. AG (n=14) groups (AG). Twelve patients were discontinued from the study. The goal AG dose was 0.5 g/kg/day. Biochemical and metabolic endpoints were measured at baseline and on day 9 (plasma Gln, antioxidant indices, lymphocyte subsets; serum IGF-1 and IGF-binding protein-3; intestinal permeability). Nitrogen balance was determined between study days 6 and 8.
  
  
  RESULTS
  Illness severity indices, clinical demographics, enteral energy and nitrogen intake and major biochemical indices were similar between groups during study. Plasma Gln was higher in the i.v. AG (565+/-119 microM, mean+/-SEM) vs the e.n. AG (411+/-27 microM) group by day 9 (p=0.039); however, subjects in the i.v. AG group received a higher dose of AG (i.v. AG 0.50 versus e.n. AG 0.32+/-0.02 g/kg/day; p<0.001). E.n. AG subjects showed a significant increase in plasma alpha-tocopherol levels over time and maintained plasma gamma-tocopherol concentrations. There were no differences between groups for plasma concentrations of vitamin C, glutathione, malondialdehyde (MDA), T-lymphocyte subsets, intestinal permeability or nitrogen balance.
  
  
  CONCLUSIONS
  This study showed that alanyl-Gln administration by enteral or parenteral routes did not appear to affect antioxidant capacity or oxidative stress markers, T-lymphocyte subset (CD-3, CD-4, CD-8) number, gut barrier function or whole-body protein metabolism compared to unsupplemented ICU patients requiring enteral tube feeding. Enteral Gln appeared to maintain plasma tocopherol levels in this pilot metabolic study.
authors.affiliation: Department of Medicine, Emory University, 1364 Clifton Road, Atlanta, GA 30322, United States.
authors.forename: Menghua
authors.initials: M
authors.lastname: Luo
authors.forename: Niloofar
authors.initials: N
authors.lastname: Bazargan
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Griffith
authors.forename: Concepción F
authors.initials: CF
authors.lastname: Estívariz
authors.forename: Lorraine M
authors.initials: LM
authors.lastname: Leader
authors.forename: Kirk A
authors.initials: KA
authors.lastname: Easley
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Daignault
authors.forename: Li
authors.initials: L
authors.lastname: Hao
authors.forename: Jon B
authors.initials: JB
authors.lastname: Meddings
authors.forename: John R
authors.initials: JR
authors.lastname: Galloway
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Blumberg
authors.forename: Dean P
authors.initials: DP
authors.lastname: Jones
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Ziegler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000378:metabolism; D003422:Critical Care; D016638:Critical Illness / Q000628:therapy*; D004151:Dipeptides / Q000276:immunology / Q000494:pharmacology*; D004311:Double-Blind Method; D004750:Enteral Nutrition; D005260:Female; D005973:Glutamine / Q000097:blood*; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009584:Nitrogen / Q000378:metabolism; D010288:Parenteral Nutrition; D010865:Pilot Projects; D012720:Severity of Illness Index; D016896:Treatment Outcome; D024502:alpha-Tocopherol / Q000097:blood; D024504:gamma-Tocopherol / Q000097:blood
chemical_list: D000975:Antioxidants; D004151:Dipeptides; D005973:Glutamine; D024504:gamma-Tocopherol; D024502:alpha-Tocopherol; D009584:Nitrogen; C054122:alanylglutamine