The citrulline generation test: Proposal for a new enterocyte function test

Abstract

Background: The amino acid citrulline is mainly produced by enterocytes from conversion of glutamine. As fasting plasma citrulline proved disappointing as a biomarker for enterocyte dysfunction in clinical practice, we propose a citrulline generation test (CGT) to assess enterocyte function. Aim: To assess the feasibility of a CGT in healthy subjects and patients with decreased enterocyte mass. Methods: Nineteen healthy subjects, 16 patients with intestinal villous atrophy and nine patients with short bowel syndrome (SBS) were given an oral bolus of 20 g of the dipeptide alanine-glutamine. Subsequent changes in plasma citrulline and other amino acid concentrations were determined using reverse-phase high-performance liquid chromatography. Results: Following the oral bolus of alanine-glutamine, plasma citrulline concentrations showed a time dependent rise in healthy subjects of 44 ± 13% (38-55 μmol/L, P < 0.0001). The slope from baseline plasma citrulline to peak concentrations was 0.22 ± 0.08, 0.13 ± 0.04 and 0.09 ± 0.04 μmol/L/min in healthy subjects, patients with coeliac disease (CeD) and refractory CeD, respectively (healthy subjects vs. CeD P < 0.05, healthy subjects vs. refractory CeD P < 0.001). In patients with SBS, the CGT was able to distinguish between non-adapted and adapted SBS by means of the incremental area under the CGT curve till 90 min (iAUC T90). The iAUC T90 was 447 ± 179 and 1039 ± 178 μmol/L/min in non-adapted and adapted SBS, respectively (P = 0.04). Conclusion: An oral bolus of alanine-glutamine induces a time-dependent rise in plasma citrulline concentration to an extent dependent on the existence of villous atrophy or enterocyte hyperplasia in CeD, and adapted SBS, respectively. © 2008 The Authors.