An In-Depth Monograph on Ornithine (DB00129): From Biochemical Pathways to Clinical and Regulatory Landscapes

Executive Summary

Ornithine is a non-proteinogenic, non-essential amino acid that occupies a central position in human nitrogen metabolism. While not incorporated into proteins via direct genetic coding, it is a critical metabolic intermediary, most notably for its indispensable role in the urea cycle, the body's primary pathway for the detoxification of ammonia.[1] Its primary, evidence-based therapeutic application is in the form of its stable salt, L-Ornithine L-Aspartate (LOLA), for the management of hyperammonemia and its neurological consequence, hepatic encephalopathy (HE). The mechanism of LOLA involves stimulating the two key ammonia detoxification pathways: urea genesis and glutamine synthesis.[4]

Beyond its clinical use, ornithine is widely marketed as a nutraceutical and dietary supplement, with claims of enhancing athletic performance, stimulating growth hormone release, reducing fatigue, and promoting muscle growth. However, a critical appraisal of the scientific literature reveals that the evidence supporting these ergogenic claims is largely conflicting, inconsistent, and often derived from studies with methodological limitations.[2]

The safety profile of ornithine is generally favorable at moderate doses, with the most common adverse effects being dose-dependent gastrointestinal disturbances.[9] A significant and serious toxicological concern, however, is the risk of retinal toxicity associated with chronic, high-dose supplementation. Sustained high plasma concentrations of ornithine have been shown to be toxic to retinal pigment epithelial cells, a risk that is particularly relevant for individuals consuming high-dose supplements for performance enhancement.[11]