Citrulline as a marker of intestinal function and absorption in clinical settings: A systematic review and meta-analysis

Background: Citrulline has been described as a marker of intestinal function or absorption but evidence varies according to clinical settings.

Objective: The objective of this article is to examine the evidence of plasma citrulline as a marker of intestinal function and absorption in various clinical settings.

Methods: Studies were examined for p values, means and standard deviations, correlation coefficients or other metrics depicting the association of citrulline with intestinal function. A random effects model was used to produce a pooled estimate. A hierarchical summary receiver operating curve model was fitted for diagnostic accuracy measures.

Results: Citrulline levels are correlated strongly with small bowel length in short bowel syndrome patients (r = 0.67). Citrulline is strongly negatively correlated (r = -0.56) with intestinal disease severity with regards to enteropathies (coeliac disease, tropical enteropathy, Crohn's disease, mucositis, acute rejection in intestinal transplantation). Citrulline cut-off levels have an overall sensitivity and specificity of 80% and 84% respectively. Citrulline levels in untreated coeliac patients compared to controls were reduced by 10 µmol/l. Citrulline levels increase with gluten-free diet and with improvement of enteropathy. Citrulline is decreased in critical illness and sepsis.

Conclusion: These findings allow us to advocate quite reasonably that citrulline is a marker of acute and chronic intestinal insufficiency.