Citrulline: Is it Ready for Primetime. Its Uses and Limitations in Neonatal Medicine

Malvika Prasad

doi:10.4172/2167-0897.1000147

Abstract

Citrulline is a non-protein amino acid produced almost exclusively by the gut and present only in small amounts in the diet. Since the gut is the main source of citrulline, it could be used as a potential biomarker of intestinal function. Necrotizing Enterocolitis is an intestinal dysfunction in neonates leading to significant morbidity and mortality. This review discusses the various aspects of intestinal injury and the association of citrulline with bowel disorders, as well as recent developments with citrulline in the pediatric population. As citrulline is directly related to small bowel length, it has been recently shown that its levels are an efficient marker when the active mass of the bowel is affected. This could be used as a prognostic marker for parenteral nutrition weaning and development of enteral tolerance. Lower levels of citrulline are found in preterm neonates with necrotizing enterocolitis and such neonates demonstrate a more prolonged course of the disease. The concomitant increase in citrulline levels along with clinical improvement in neonates and progression of enteral feeds suggest that citrulline levels may be a sensitive marker of intestinal recovery. Studies have shown that citrulline levels are well correlated with the length of the bowel as well as intestinal function. Citrulline levels used as a sensitive biomarker for intestinal absorptive function would be clinically useful in diagnosis of necrotizing enterocolitis and detection of bowel function and recovery from intestinal disorders such as necrotizing enterocolitis, although more studies are needed in newborns affected with these diseases.

Highlights

L-Citrulline is a naturally occurring non-essential amino acid, an intermediate of the urea cycle and a potent hydroxyl radical scavenger
Citrulline produced by the enterocyte enters the urea cycle as an intermediate in the production of arginine, an amino acid that has key roles in protein synthesis, ammonia detoxification, nitric oxide production [4]
Many studies have demonstrated that citrulline as a marker of functional enterocyte mass, lower citrulline levels are expected in preterm neonates with necrotizing enterocolitis

Summary

Introduction

L-Citrulline is a naturally occurring non-essential amino acid, an intermediate of the urea cycle and a potent hydroxyl radical scavenger. Studies among adult populations have found a significant correlation between post-absorptive plasma citrulline level and remnant small bowel length. Small bowel syndrome patients have shown significant correlation between plasma citrulline levels postsurgery and the remnant bowel length [20,21]. Previous studies have shown significant correlations between citrulline levels and parenteral nutrition dependence in the small bowel syndrome patients. Crenn et al [1] demonstrated, a fasting citrulline less than 20 μmol/L was related to inability to wean home parenteral nutrition among adult patients from following an intestinal adaptation phase of 24 months. Many studies have demonstrated that citrulline as a marker of functional enterocyte mass, lower citrulline levels are expected in preterm neonates with necrotizing enterocolitis. Two studies [23,29] though prospective performed are observational further studies are needed to measure citrulline levels as a guide to the clinical management of neonates, especially among preterm to predict starting, recovery and prognosis of necrotizing enterocolitis (Table 1)

Major Findings

Findings

Conclusion