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.

Objectives: 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.

Figure 1. Study design

Eligible medical and surgical ICU subjects were assigned in a double-blind, block randomization format to one of three isonitrogenous, isocaloric study groups; control (tube feeds + daily intravenous Gln-free amino acids), intravenous alanyl-Gln dipeptide (IV AG; tube feeds + daily intravenous Gln dipeptide) or enteral alanyl-Gln dipeptide (EN AG; tube feeds + daily enteral Gln dipeptide added to tube feeds). All patients received a standard polymeric tube feeding formula. Block randomization was based on APACHE II illness severity. Major endpoints were determined at baseline and again on study day 9 and nitrogen balance was estimated between study days 6 and 9.

Figure 2. Plasma glutamine concentrations

Plasma glutamine concentrations were higher in the IV AG group versus the control and EN-AG groups after 8 days of treatment. ^* p=0.039 versus baseline values.

Figure 3. Plasma indices of antioxidant capacity

Compared with the baseline values, plasma glutathione peroxidase GSHPX was decreased in the enteral alanyl-Gln group (panel a). However, enteral alanyl-Gln supplementation increased plasma α-tocopherol concentrations (panel d) and maintained plasma γ-tocopherol concentrations (panel e), compared to the other two study groups, in which no change in plasma α-tocopherol or a fall γ-tocopherol occurred. Plasma zinc concentrations were increased from baseline to day 9 in the control group and IV alanyl-Gln group, while no change was observed in the enteral AG group (panel f). Plasma GSH concentrations remained unchanged among the three treatment groups (panel g). ^* p=0.049; ^** p=0.019; ^† p=0.011 versus baseline values.