Hepatoprotection by L-Ornithine L-Aspartate in Non-Alcoholic Fatty Liver Disease

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is the leading chronic hepatic condition worldwide and new approaches to management and treatment are limited. Summary: L-ornithine L-aspartate (LOLA) has hepatoprotective properties in patients with fatty liver of diverse etiology and results of a multicenter randomized clinical trial reveal that 12 weeks treatment with oral LOLA (6–9 g/d) results in a dose-related reduction in activities of liver enzymes and triglycerides together with significant improvements of liver/spleen CT ratios. A preliminary report described improvements of hepatic microcirculation in patients with non-alcoholic steatohepatitis (NASH) following treatment with LOLA. Mechanisms responsible for the beneficial effects of LOLA in NAFLD/NASH involve, in addition to its established ammonia-lowering effect, metabolic transformations of the LOLA-constituent amino acids L-ornithine and L-aspartate into L-glutamine, L-arginine, and glutathione. These metabolites have well-established actions implicated in the prevention of lipid peroxidation, improvement of hepatic microcirculation in addition to anti-inflammatory, and anti-oxidant properties. Key Messages: (1) LOLA is effective for the treatment of key indices in NAFLD/NASH. (2) Mechanisms other than LOLA’s ammonia-lowering action have been postulated. (3) Further assessments in the clinical setting are now required.

Hepatoprotective effect of a novel lactic acid‐fermented garlic extract functional food product against acute liver injury

“…It was also shown that l ‐arginine improved hepatic microcirculation following ischemia‐reperfusion injury (Uhlmann, Scommotau, Witzigmann, & Spiegel, ). Clinically, a mixture of l ‐ornithine and l ‐aspartate (LOLA) has been shown to have hepatoprotective properties in individuals with fatty liver diseases (Butterworth & Canbay, ). Such hepatoprotection seems to result from the transamination of l ‐ornithine into glutamate (Butterworth & Canbay, ).…”

“…Clinically, a mixture of l-ornithine and l-aspartate (LOLA) has been shown to have hepatoprotective properties in individuals with fatty liver diseases (Butterworth & Canbay, 2019). Such hepatoprotection seems to result from the transamination of l-ornithine into glutamate (Butterworth & Canbay, 2019). Indeed, IV infusion of LOLA in patients with chronic liver disease induced an increase in plasma glutamate, and subsequently restored glutamine levels (Staedt et al, 1993).…”

“…Most importantly, it is well-known for its hepatoprotective, antioxidative, antimicrobial, anti-inflammatory, and immune-regulatory activities (Kao, Wu, & Yen, 2014;Wang, Yang, Yuan, Liu, & Liu, 2015;Yang, Yuan, Ma, Zhou, & Liu, 2017). l-arginine is the precursor of nitric oxide (NO) and has been known to play various roles in animals including hepatoprotection (Kurokawa et al, 2012;Ozsoy et al, 2011;Stuehr, 2004); l-ornithine is known for its role in ammonia removal and thus is currently used to treat cirrhosis in humans (Butterworth & Canbay, 2019;Durgun et al, 2015). We have recently developed an advanced hepatoprotective food product named D-18-007, a LAFGE (Choi et al, 2014)-based product that had been reformulated to contain the extracts of artichoke and licorice as well as l-arginine and l-ornithine.…”

L-Ornithine L-Aspartate for the Treatment of Sarcopenia in Chronic Liver Disease: The Taming of a Vicious Cycle

“…Finally, the focus of the present review has principally been directed at the potential benefits of LOLA treatment for sarcopenia in cirrhosis. However, there is emerging evidence to support the notion that it may also be beneficial in patients with sarcopenia related to NAFLD/NASH [29]. For example, in a study of 463 patients with fatty liver, 29% of whom were nonalcoholic, treated with oral LOLA for up to 60 days, significant decreases of liver enzymes [30] were noted and in a subsequent RCT, 72 patients treated with oral LOLA for 12 weeks manifested significant dose-related reductions of transaminases together with decreases in triglycerides and improvements in liver/spleen ratios [31].…”

L-Ornithine L-Aspartate: Multimodal Therapeutic Agent for Hyperammonemia and Hepatic Encephalopathy in Cirrhosis

“…Studies of the potential mechanisms responsible for the hepatoprotective properties of LOLA are few in number and are currently focused on the synthesis of agents derived from the conversion of the constituent amino acids of LOLA to agents with established anti-oxidant properties such as glutathione (GSH) and glutamine [21]. Figures 2a and 2b above and the synthesis of glutamine from glutamate occurs readily in liver and skeletal muscle via the enzyme GS (Figure 2d).…”