Effects of Monacolin K in Nondiabetic Patients with NAFLD: A Pilot Study

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver condition with significant risk of progression to steatohepatitis and cirrhosis. Therapeutic strategies in NAFLD include lifestyle changes mainly related to dietary interventions and use of drugs or nutritional components that could improve plasma lipid profiles and insulin sensitivity and decrease the local inflammatory response. In this study, we tested the effects of monacolin K, an inhibitor of HMCoA reductase. In a prospective, uncontrolled, open study, we treated 24 patients with NAFLD and mild hypercholesterolemia with 10 mg/day of monacolin K. At baseline and after 26 weeks, we measured in plasma liver tests, lipids, malondialdehyde, and oxidized glutathione, and assessed biochemical steatosis scores, liver elastography, and body composition with bioimpedance analysis. Monacolin K significantly reduced plasma alanine aminotransferase, cholesterol, triglycerides and the homeostatic model assessment (HOMA) index that indicated improved insulin sensitivity. No significant changes were found in body fat mass and visceral fat, nor in liver elastography, while the fatty liver index (FLI) was significantly decreased. Plasma levels of both malondialdehyde and oxidized glutathione were markedly reduced by monacolin K treatment, suggesting a reduction in oxidative stress and lipid peroxidation. In summary, this pilot study suggests possible benefits of monacolin K use in NAFLD patients that could be linked to a reduction in oxidative stress. This hypothesis should be further investigated in future studies.

Keywords: bioimpedance; glutathione; liver fibrosis; liver steatosis; liver ultrasound; malondialdehyde.

Figure 1

Box plot of baseline and follow-up plasma malondialdheyde and oxidized glutathione levels in 24 NAFLD patients that were treated for 26 weeks with monacolin K.