L-Ornithine L-Aspartate in Acute Treatment of Severe Hepatic Encephalopathy

Recently, researchers have studied L-ornithine L-aspartate and its efficacy in the treatment of hepatic encephalopathy. Two oral formulations of L-ornithine-L-aspartate were studied in healthy volunteers. Another study, by Lamparczyk H and Kruger B, studied Ornithine-L-aspartate and its effects on human plasma.


This study sought to assess the efficacy of L-ornithines L-aspartate (LOLA) as an acute treatment for severe hepatic encephalopathy. The drug can be given via oral or parenteral routes, and it may be administered in any dose or duration. The authors performed a comprehensive search to identify relevant studies. Specifically, they searched PubMed, LILACS, SciELO, and the Cochrane Collaboration Register of Controlled Trials.

The study involved eight patients with cirrhosis. Each participant had a portal catheter inserted for 24 hours to measure ammonia levels on two consecutive days. Participants also underwent electroencephalography and psychometric tests. During the study, participants received oral glutamine 20 mg, placebo, or one dose of LOLA. All infusions were administered by a double-blind method. The intervention had no effect on either the patients’ ammonia levels or the primary outcomes of the study.

Efficacy in reducing brain edema

Ammonia is one of the leading causes of neurological abnormalities in patients with liver disease. Approximately 15% of ammonia production occurs in the bowel. Therefore, a key part of management in this disease involves limiting ammonia generation in the bowel and manipulating systemic mechanisms of ammonia metabolism. As a dietary supplement, L-ornithine-L-aspartate has been shown to improve mental status and reduce serum ammonia levels, as well as increase glutamine synthesis in perivenous “scavenger” hepatocytes.

LOLA known as amino acids with a molecular formula of C9H19N3O6 and is freely soluble in water and ethanol. In the body, it is converted to alanine, glutamate, and urea. In the liver, aspartate oxidizes oxaloacetate. In addition, residual aspartate can combine with citrulline to form arginine-succinate, which in turn cleaves to fumarate.

Efficacy in lowering blood ammonia levels

Efficacy was measured as the time to confirmed clinical response to L-ornithine L-Aspartate in patients with acute hepatic encephalopathy. Response was defined as a reduction of HEST stage from baseline or an improvement to HEST stage 0/1 or -2. The time was calculated from the start of drug infusion to the first of two assessments that met the response criteria. If the patient was discharged before the second assessment, time to the second assessment was recorded. Post-hoc exploratory analyses were conducted in patients with baseline ammonia levels greater than the ULN determined by the central laboratory.

In a study by Kowalski P and Bieniecki M, ornithine-L-aspartate significantly decreased levels of ammonia and amino acids in livers with hepatic encephalopathy. The authors also studied the efficacy of L-ornithine-L-aspartate in human plasma.

Hepatoprotective properties

A recent study published in the J Coll Phys Surg Pak highlighted the efficacy of L-ornithine L’aspartate in acute treatment of severe cases of hepatic encephalopathy. It also concluded that L-ornithine L’aspartate was effective in patients with cirrhosis and hepatic encephalopathy. The study involved a meta-analysis of randomized controlled trials to evaluate the efficacy of L-ornithine L’aspartate in acute treatment of severe hepatic encephalopathy.

In a controlled trial, L-ornithine L’aspartate (LOLA) rescued the liver after chronic CCl4 administration. However, this drug is not safe in humans. Although it is not proven to be effective in treating severe hepatic encephalopathy, it is a promising therapy for asymptomatic liver disease.

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