Ornithine

Ornithine is an amino acid that, unlike the twenty standard amino acids, is not incorporated into proteins; instead it functions mainly as a metabolic intermediate ^[1]. It sits at the heart of the urea cycle, also called the ornithine cycle, a series of reactions in the liver that convert toxic ammonia into urea for excretion ^[1]. Within this cycle ornithine acts catalytically: it combines with a carbamoyl group to begin forming urea and is regenerated at the end of each turn, so it is continually reused rather than consumed ^[1].

Ornithine is chemically related to arginine and citrulline, and the three interconvert within the urea cycle ^[1]. The enzyme arginase breaks down arginine to yield urea and ornithine, while ornithine can be converted onward to citrulline; ornithine also serves as a precursor for other important molecules, including the polyamines and the amino acid proline. The compound was first identified in the nineteenth century, its name deriving from a Greek word for bird, reflecting its early isolation from bird excrement.

Interest in ornithine as a supplement follows from its role in handling ammonia ^[1][2]. Its best-established medical use is as L-ornithine L-aspartate (LOLA), a salt of ornithine and aspartate used to lower raised blood ammonia and to treat hepatic encephalopathy, the confusion and impaired brain function that can arise in advanced liver disease; the two amino acids feed reactions that lock ammonia into urea and glutamine ^[1]. Separately, small studies in healthy people have examined L-ornithine for exercise and fatigue: controlled trials reported that ornithine can enhance the body's ability to clear the ammonia produced during exertion and may reduce the subjective feeling of fatigue, though it did not clearly improve exercise performance itself ^[2][3].

Ornithine is sold as a dietary supplement in the form of L-ornithine and L-ornithine hydrochloride, sometimes combined with arginine, and as the medically used L-ornithine L-aspartate ^[1][3]. LOLA is available in oral and intravenous forms in a number of countries for liver-related use, whereas plain L-ornithine supplements are marketed for general wellness and exercise recovery ^[1]. As a naturally occurring amino acid it is generally well tolerated, with digestive upset the most common complaint at higher intakes ^[3].

Very well tolerated; the most common side effect at higher doses is loose stools or GI cramping. It is not associated with serious risks in healthy people. Those with kidney or liver disease should be cautious given its role in nitrogen handling.