Citrulline increases arginine pools and restores nitrogen balance after massive intestinal resection

Abstract

Objective: Arginine supplementation seems logical in situations where this amino acid becomes essential, for example after massive intestinal resection. Arginine is taken up and metabolised by the liver to a large extent and its supplementation is potentially unsafe. Citrulline is not captured by the liver and passes freely to the kidneys where it is metabolised to arginine, and so is a good candidate to generate arginine and thereby improve nutritional status.

Methods: Twenty four rats were assigned to four groups: citrulline, arginine, control, and sham. The sham group underwent transection and the three other groups resection of 80% of the small intestine. All rats were fed by enteral nutrition and its composition was as follows: supplementation with citrulline in the citrulline group, supplementation with arginine in the arginine group, and standard polymeric enteral nutrition in the control and sham groups. All groups received isonitrogenous nutrition and citrulline and arginine intakes were equimolar in their respective groups. After 10 days, the rats were sacrificed.

Results: Arginine concentration was higher (p<0.05) in plasma and muscle in the citrulline group than in the three other groups. Plasma levels of arginine were 110 (12), 79 (7), 167 (22), and 228 (13) mumol/l in the sham, control, arginine, and citrulline groups respectively. Arginine concentrations in the gastrocnemius were: 0.15 (0.02), 0.16 (0.02), 0.40 (0.05), and 0.94 (0.20) mumol/g, respectively. Citrulline preserved nitrogen balance in resected rats but not in arginine supplemented rats (mean J10: 2.27 (0.29), 1.67 (0.15), 1.98 (0.29), and 2.43 (0.41) g/24 hours in the sham, control, arginine, and citrulline groups, respectively).

Conclusion: Supplementing the diet with citrulline is a very efficient means of increasing arginine levels and improving nitrogen balance after massive intestinal resection. The results of this study form a strong rationale for citrulline supplementation in these patients.

Figures

Figure 1

Plasma citrulline, ornithine, and arginine concentrations at the end of the enteral nutrition programme. Four groups of rats were studied: sham (transected rats fed standard enteral nutrition), control (resected rats fed standard enteral nutrition), arginine (Arg; resected rats fed arginine supplemented diet), citrulline (Cit; resected rats fed citrulline supplemented diet). Results are expressed as mean values (SEM). Values with different superscript letters are statistically different.

Figure 2

Nitrogen balance during 10 days of total enteral nutrition. Four groups of rats were studied: sham (transected rats fed standard enteral nutrition), control (resected rats fed standard enteral nutrition), arginine (resected rats fed arginine supplemented diet), and citrulline (resected rats fed citrulline supplemented diet). Results are expressed as the difference between daily nitrogen intake and daily urinary nitrogen excretion. Results are presented as mean values (SEM). *p