Yellow Yeast Rice Prepared Using Aspergillus terreus DSMK01 Lowers Cholesterol Levels by Stimulating Bile Salt Export Pump in Subjects with Mild-to-Moderate Hypercholesterolemia: A Randomized Controlled Trial

Scope: Aspergillus terreus is an industrial microorganism used in the brewing and sauce industries. It produces monacolin K, a natural statin. The study conducted an 8-week randomized controlled trial with hypercholesterolemic subjects to examine the hypocholesterolemic effects and mechanisms of supplementation with yellow yeast rice (YYR) prepared by growing Aspergillus fungi on steamed rice. Methods and Results: YYR supplementation markedly reduced total cholesterol, LDL, and apolipoprotein B100 levels in plasma compared with the placebo. In addition, YYR induced a significantly increased ATP binding cassette subfamily B member 11 (ABCB11) gene expression compared with the placebo, indicating the role of YYR in lowering intrahepatic cholesterol availability by stimulating the bile salt export pump. Upregulation of LDL receptor (LDLR) and 3-methylglutaryl-CoA reductase (HMGCR) gene expressions provided additional evidence to support the role of YYR in reducing hepatic cholesterol availability. Plasma metabolomic profiling revealed the possibility of diminishing bile acid absorption. Finally, Spearman rank analysis showed correlations of plasma cholesterol profiles with HMGCR and LDLR gene expressions (negative) and plasma bile acids (positive). Plasma bile acids also correlated with ABCB11 (negative) and LDLR (positive) gene expressions. Conclusion: These findings suggest that daily YYR supplementation exerted hypocholesterolemic effects in mild-to-moderate hypercholesterolemic subjects by reducing intrahepatic cholesterol availability through stimulating bile salt export pumps and inhibiting cholesterol biosynthesis.