L-Citrulline for Urea Cycle Disorders in Adults - Review

Key Findings

This review confirms L-citrulline is a standard nitrogen-scavenging therapy for specific urea cycle disorders (UCDs) in adults, particularly ornithine transcarbamylase deficiency and citrullinemia. It serves as an alternative to arginine supplementation to maintain nitrogen balance and prevent hyperammonemia-induced encephalopathy. No quantitative efficacy data (e.g., ammonia reduction percentages, p-values) are reported, as the study synthesizes existing clinical knowledge rather than presenting new trial results. The primary conclusion is that timely diagnosis and treatment—including L-citrulline—are critical for managing adult-onset UCDs to avoid neurological complications.

Study Design

This is a narrative review article (not an original clinical trial) analyzing current understanding of urea cycle disorders in adults. It synthesizes evidence from existing literature on UCD pathophysiology, diagnosis, and management. No original patient data, sample size, study duration, or demographic details (e.g., age, sex) are provided, as the work aggregates findings from prior studies rather than conducting new research.

Dosage & Administration

The review states L-citrulline is administered orally as part of conservative therapy for UCDs but does not specify exact doses, frequency, or formulation. It notes citrulline is used "in place of arginine" for certain UCDs (e.g., ornithine transcarbamylase deficiency) to bypass metabolic blocks, but quantitative dosing protocols (e.g., mg/kg/day) are not detailed in this summary. Administration is described as lifelong, integrated with protein-restricted diets and other nitrogen-scavenging agents.

Results & Efficacy

No original efficacy data are presented. The review asserts L-citrulline reduces hyperammonemia risk by replenishing urea cycle intermediates, but no effect sizes, statistical significance (p-values), or confidence intervals are provided. Efficacy is framed as clinical consensus: citrulline "should be considered" for long-term management, with success defined by normalized ammonia levels and prevention of encephalopathy. No comparative data (e.g., citrulline vs. arginine) are included.

Limitations

As a review, this study has no original data collection, limiting direct applicability. Key gaps include:
- Absence of dosing specifics, long-term outcomes, or head-to-head treatment comparisons.
- Reliance on heterogeneous prior studies without meta-analysis.
- No discussion of citrulline’s efficacy in non-UCD populations (e.g., healthy adults).
Future research needs highlighted include optimizing scavenger regimens and evaluating liver transplantation outcomes.

Clinical Relevance

L-Citrulline is strictly relevant as a medical therapy for diagnosed urea cycle disorders, not as a general supplement. For UCD patients, it prevents life-threatening hyperammonemia but requires physician supervision. This study provides zero evidence for L-citrulline use in healthy adults (e.g., for exercise performance or blood pressure). Users without UCDs should not extrapolate benefits; self-supplementation could mask undiagnosed metabolic issues. Clinicians must confirm UCD diagnosis via genetic/metabolite testing before prescribing.