Absorption, Distribution, and Biliary Excretion of Cafestol, a Potent Cholesterol-Elevating Compound in Unfiltered Coffees, in Mice

Abstract

ABSTRACT: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 3 H-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 h after administration. Next, radiolabeled cafestol was dosed intravenously to bile duct-cannulated mice.Five hours after the 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 the 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 gastrointestinal tract, we hypothesized 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 tract.

Decaffeinated Coffee and Nicotine-Free Tobacco Provide Neuroprotection in Drosophila Models of Parkinson's Disease through an NRF2-Dependent Mechanism

“…Although this finding could ultimately lead to the development of a preventative therapy for PD, it is unclear that cafestol itself represents a good candidate for therapeutic intervention because cafestol also potently elevates serum cholesterol through an unknown mechanism (van Cruchten et al, 2010), and serum cholesterol levels correlate with heart disease risk (Stamler et al, 2000). However, it is possible that a structural analog of cafestol can be identified that retains the neuroprotective feature of cafestol but lacks its cholesterol-elevating property.…”

The Pocket-4-Life project, bioavailability and beneficial properties of the bioactive compounds of espresso coffee and cocoa-based confectionery containing coffee: study protocol for a randomized cross-over trial

“…Volunteers will also be supplied with the cocoa-based product containing coffee (Pocket Coffee, Ferrero Commerciale Italia S.r.l., Alba, Italy). The content in phytochemicals of the coffee and the cocoa-based product containing coffee will be analyzed by ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) following methodologies described in previous reports [ 32 – 35 ]. Accurate calibration and absolute quantification will be achieved by comparison with authentic standards.…”

“…Plasma samples will be extracted according to Zhang et al [ 39 ], while urine samples will be centrifuged, diluted, and filtered. Methylxanthines, trigonelline, other pyridine metabolites, diterpenes, and phenolic metabolites will be determined as previously described [ 32 – 35 ]. Accurate calibration and absolute quantification will be achieved by comparison with authentic standards when commercially available or with standards previously synthesized [ 40 , 41 ].…”

Tea, Coffee, and Chocolate

“…Cafestol, a diterpene, is the most potent cholesterolelevating compound present in the human diet, although it also has a hepatoprotective effect [11]. Cafestol, a diterpene, is the most potent cholesterolelevating compound present in the human diet, although it also has a hepatoprotective effect [11].…”