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

Abstract

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.

Keywords: Citrulline; enteropathy; meta-analysis; short bowel syndrome; systematic review.

Figures

Figure 1.

Flowchart for systematic review of studies.

Figure 2.

Risk of bias graph: Review authors’ judgements about each risk of bias item presented as percentages across all included studies (all studies).

Figure 3.

Forest plot. Correlation coefficient with small bowel length in short bowel syndrome. CI: confidence interval. IV: Inverse Variance.

Figure 4.

Funnel plot. Correlation coefficient with small bowel length in short bowel syndrome – there is asymmetry in the plot indicating publication bias.

Figure 5.

(a) Forest plot with overall weighted mean difference of patients with a condition against controls (30 studies). (b) Forest plot with correlation coefficients with severity in all available studies (28 studies). CI: confidence interval. IV: Inverse Variance, SD: Standard Deviation.

Figure 5.

(a) Forest plot with overall weighted mean difference of patients with a condition against controls (30 studies). (b) Forest plot with correlation coefficients with severity in all available studies (28 studies). CI: confidence interval. IV: Inverse Variance, SD: Standard Deviation.

Figure 6.

Summary receiver operating characteristic (SROC) curve for all studies of diagnostic accuracy (26 studies). SENS: sensitivity; SPEC: specificity; AUC: area under the curve.

Figure 7.

Forest plot with correlation coefficients of citrulline levels with enteral absorption (14 studies). CI: confidence interval. IV: Inverse variance.