What is L-arginine L-aspartate?

L-Ornithine L-Aspartate: Composition, Function, and Clinical Applications

L-ornithine L-aspartate (LOLA) is a stable salt of two naturally occurring amino acids that functions primarily as an ammonia-lowering agent in liver disease and plays a role in multiple metabolic pathways including the urea cycle and glutamine synthesis.

Composition and Basic Properties

L-ornithine L-aspartate consists of two amino acids:

• L-ornithine: A non-essential amino acid involved in the urea cycle
• L-aspartate: A non-essential amino acid that participates in multiple metabolic pathways

Biochemical Functions

LOLA works through two primary mechanisms:

• Ammonia detoxification:

  • Enhances urea synthesis in periportal hepatocytes (via L-ornithine)
  • Promotes glutamine synthesis in perivenous hepatocytes and skeletal muscle (via both components) 1

• Metabolic roles:

  • Serves as substrates for the urea cycle
  • Contributes to proline and polyamine biosynthesis
  • Supports tissue regeneration and wound healing 2

Clinical Applications

1. Hepatic Encephalopathy

LOLA is primarily used in the management of hepatic encephalopathy:

• Dosage: Typically administered as 30g/day intravenously in clinical settings 1
• Efficacy: Studies show LOLA can:
  • Reduce recovery time from hepatic encephalopathy (1.92 vs 2.50 days compared to lactulose alone) 1
  • Lower plasma ammonia concentrations 1
  • Potentially reduce mortality and serious adverse events in acute-on-chronic liver failure 1

2. Non-Alcoholic Fatty Liver Disease (NAFLD)

Emerging research suggests potential benefits in NAFLD:

• May lower liver ammonia concentrations
• Provides anti-oxidative glutamine and glutathione
• Currently under investigation for hepatoprotective effects 3

3. Other Potential Applications

• Tissue regeneration: Polyamines derived from ornithine stimulate hepatic regeneration 2
• Wound healing: Animal studies show enhanced wound breaking strength and collagen deposition with ornithine supplementation 2

Clinical Considerations

• Formulations:

  • Low doses (around 1g/day): Used as food supplements
  • High doses (above 5g): Used as medicinal products for hepatic encephalopathy 2

• Safety profile:

  • Generally well-tolerated at therapeutic doses
  • No major adverse effects reported in clinical trials 1

Important Distinctions

It's important to distinguish LOLA from L-arginine L-aspartate:

• L-arginine is a precursor for nitric oxide (NO) synthesis and has different clinical applications related to vascular function 4, 5
• While both compounds contain L-aspartate, their primary clinical uses differ significantly

Clinical Practice Guidelines

Current guidelines suggest:

• LOLA may be used in acute-on-chronic liver failure patients with overt hepatic encephalopathy (conditional recommendation, very low quality evidence) 1
• LOLA is not routinely recommended for acute liver failure patients with hyperammonemia due to insufficient evidence 1
• LOLA is included in pharmacological options for managing overt hepatic encephalopathy at a dose of 30g/day intravenously 1

In summary, LOLA represents an important therapeutic option primarily for hepatic encephalopathy, with emerging applications in other liver conditions based on its ammonia-lowering properties and metabolic functions.