L-ornithine L-aspartate (LOLA) has been an effective ammonia-lowering agent for over 50 years, with good evidence in hepatic encephalopathy. Administration of LOLA clears ammonia through two different mechanisms: by synthesizing urea and by synthesizing glutamine via the enzyme glutamine synthetase. 

Although LOLA is widely used in cirrhosis and acute liver injury settings, its role in non-alcoholic fatty liver disease (NAFLD) remains unclear. NAFLD and the progressive form of non-alcoholic steatohepatitis (NASH) make the major cause of chronic liver disease globally, with approximately 25% of the world population affected by NAFLD. NASH may terminate to end-stage liver disease and cardiovascular morbidity and mortality. 

Since excess calorie uptake and excess adipose tissue mass comprise the etiology of NAFLD, the conservative therapeutic approach of weight loss by intense lifestyle change is advisable. However, we still await pharmacological treatment options for approval. 

LOLA is now investigated as a pharmacological tool to ameliorate liver injury in NAFLD since it lowers liver ammonia concentrations and supplies anti-oxidative glutamine and glutathione. Indirect hepatoprotective effects, which are currently under investigation, may also prove beneficial.

Canbay A, Sowa JP. L-Ornithine L-Aspartate (LOLA) as a Novel Approach for Therapy of Non-alcoholic Fatty Liver Disease. Drugs. 2019; 79 (1): 39–44. https://doi.org/10.1007/s40265-018-1020-5