A Comprehensive Pharmacological and Clinical Monograph on L-Citrulline (DB00155)

Executive Summary

L-Citrulline is a non-proteinogenic α-amino acid with a unique and multifaceted role in human physiology. While endogenously synthesized, its therapeutic and supplemental applications stem from a distinctive pharmacological profile, primarily its function as a highly bioavailable precursor to L-arginine. This report provides an exhaustive analysis of L-Citrulline, synthesizing its chemical properties, metabolic pathways, clinical pharmacology, therapeutic efficacy, and safety profile.

A central finding of this monograph is the "Citrulline Paradox": oral administration of L-citrulline is a more effective strategy for increasing systemic L-arginine levels than supplementing with L-arginine itself. This is due to L-citrulline's ability to bypass the extensive first-pass metabolism in the gut and liver that significantly limits L-arginine's bioavailability. This superior pharmacokinetic profile is the foundation for its clinical applications, which are primarily mediated by the subsequent enhancement of the L-arginine-nitric oxide (NO) pathway.