LOLA in NAFLD/MASH

The clinical data on the use of LOLA in NAFLD/NASH is limited as compared to the clinical data on the use of LOLA to manage Hepatic Encephalopathy.

While the clinical data in NAFLD/NASH is limited, the use of LOLA is promising and may be of benefit to appropriate patients.

The clininical data support the consideration of treating NAFLD/NASH pateints with elevated ammonia and those with cognitive impairment due to elevated ammonia.

Mechanism of action of LOLA in NAFLD/MASH

The beneficial effect of LOLA on NAFLD/NASH involve the ammonia lowering effect of LOLA as well as the potential metabolic transformations of the LOLA constituent amino acids into L-glutamine, L-arginine, and glutathione. These metabolites have been implicated in the prevention of lipid peroxidation, and anti-inflammatory and anti-oxidant properties.

Some research has also indicated lowering ammonia in itself has a benefit in NAFLD/NASH by improving hepatic microcirculation.

HepLOLA doing in NAFLD/MASH

LOLA dosing in the clinical trials in the NAFLD/NASH setting indicates that 6g BID is the most effective dose.

As a comparison, LOLA dosing in Hepatic Encephalopathy is typically 6g TID.

A canister of HepLOLA has 90 6g doses.

LOLA in Chronic Liver Disease, including NAFLD/MASH in 463 patients. Potential Hepato-Protective properties

  • In a groundbreaking report of HepLOLA in 463 patients with fatty liver, 29% of whom were nonalcoholic, LOLA reduced ASAT, ALT and y-GT by up to 70%
  • HepLOLA has shown a reduction in ALT from 52.6 to 39.2
  • HepLOLA has shown a reduction in AST from 48.1 to 25.7

  • Efficacy of L-Ornithine L-Aspartate granules in chronic liver disease. Grungreiff K, Lambert-Baumann J, Med Welt 2001, 219
Link to publication

Dose comparison of LOLA in NASH in 72 patients.

  • Aspartate ornithine granules in the treatment of nonalcoholic steatohepatitis: A multiple-dose parallel controlled clinical trial.
Link to publication

LOLA improves intrahepatic microcirculation in NASH.

  • Correction of intrahepatic microcirculation disorders by L-Ornithine L-Aspartate at the chronic liver disease patients. Journal of Hepatology 2018
Link to abstract

Elevated ammonia in NASH is associated with Cognitive Impairment.

  • Graph that shows contribution of hyperammonemia and inflammatory factors to cognitive impairment in minimal hepatic encephalopathy. Metabolic Brain Disorders 2012. The graph shows that patients NASH/MASH with Chronic Liver Disease have the largest reduction in cognitive impairment.
Link to Publication

Ammonia as a target in treating NAFLD/NASH

  • Clinical trial titled: Ammonia: A novel target for the treatment of non-alcoholic steatohepatitis. Published in Medical Hypotheses 2018
Link to publication

Editorial on potential hepatoprotection with LOLA in NAFLD/NASH

  • Clinical Editorial on the Hepatoprotection of HepLOLA L-Ornithine L-Aspartate in Non-alcoholic Fatty Liver Disease. Published in Digestive Disease 2019
Link to editorial

Editorial on LOLA as a therapy for NAFLD/NASH.

  • Clinical Editorial titled: L-Ornithine L-Aspartate (LOLA) as a novel approach for Therapy of Non-Alcoholic Fatty Liver disease. Pubblished in the Journal Drugs in 2019
Link to publication