Absorption, distribution and biliary excretion of cafestol, a potent cholesterol elevating compound in unfiltered coffees in mice

Cafestol is a diterpene present in unfiltered coffees. It is the most potent cholesterol-elevating compound present in the human diet. However, the precise mechanisms underlying this effect are still unclear. In contrast, cafestol is also known as a hepatoprotective compound which is likely to be related to the induction of glutathione biosynthesis and conjugation. In the present study we investigated whole body distribution, biliary excretion and portal bioavailability of cafestol in mice. First, dissection was used to study distribution. Five hours after an oral dose with 3H labeled cafestol, most activity was found in small intestine, liver and bile. These results were confirmed by quantitative whole body autoradiography in a time course study which also showed elimination of all radioactivity within 48 hours after administration. Next, radiolabeled cafestol was dosed i.v. to bile duct cannulated mice. Five hours post dose 20% of the radioactivity was found in bile. Bile contained several metabolites but no parent compound. After intestinal administration of radioactive cafestol to portal vein cannulated mice, cafestol was shown to be rapidly absorbed into the portal vein as parent compound, a glucuronide and an unidentified metabolite. From the presence of a glucuronide in bile that can be deconjugated by a bacterial enzyme and the prolonged absorption of parent compound from the GI tract we hypothesize that cafestol undergoes enterohepatic cycling. Together with our earlier observation that epoxidation of the furan ring occurs in liver these findings merit further research on the process of accumulation of this coffee ingredient in liver and intestinal trac