Cafestol

The extraction yield of cafestol from roast and ground (R&G) coffee beans was evaluated using brews prepared by four brewing mechanisms (boiled, Turkish, French Press and Mocha Pot). The cafestol content of the R&G coffee and the resulting brews was measured and extraction yield calculated. The R&G coffee had an average cafestol content of 603 mg/100 g R&G coffee with a slight reduction at higher roast intensities. In the brews, preparation method had an impact on cafestol concentration with French, Turkish and boiled preparation methods producing the highest cafestol concentrations. The extraction yield of cafestol was shown to be dependent on the brew mechanism and roasting time, with the lightest roast coffee prepared by French press or boiled preparations having the highest cafestol extraction yield (6.5% and 5.84%) and dark roast Mocha and Turkish preparations had the lowest extraction yields of 2.42% and 2.88% respectively.

—Cafestol, a diterpene present in unfiltered coffee, potently increases serum cholesterol levels in humans. So far, no suitable animal model has been found to study the biochemical background of this effect. We determined the effect of cafestol on serum cholesterol and triglycerides in different mouse strains and subsequently studied its mechanism of action in apolipoprotein (apo) E*3-Leiden transgenic mice. ApoE*3-Leiden, heterozygous low density lipoprotein– receptor (LDLR/) knockout, or wild-type (WT) C57BL/6 mice were fed a high-(0.05% wt/wt) or a low-(0.01% wt/wt) cafestol diet or a placebo diet for 8 weeks. Standardized to energy intake, these amounts are equal to 40, 8, or 0 cups of unfiltered coffee per 10 MJ per day in humans. In apoE*3-Leiden mice, serum cholesterol was statistically significantly increased by 33% on the low-and by 61% on the high-cafestol diet. In LDLR/ and WT mice, the increases were 20% and 24%, respectively, on the low-cafestol diet and 55% and 46%, respectively, on the high-cafestol diet. These increases were mainly due to a rise in very low density lipoprotein (VLDL) and intermediate density lipoprotein cholesterol in all 3 mouse strains. To investigate the mechanism of this effect, apoE*3-Leiden mice were fed a high-cafestol or a placebo diet for 3 weeks. Cafestol suppressed enzyme activity and mRNA levels of cholesterol 7-hydroxylase by 57% and 58%, respectively. mRNA levels of enzymes involved in the alternate pathway of bile acid synthesis, ie, sterol 27-hydroxylase and oxysterol 7-hydroxylase, were reduced by 32% and 48%, respectively. The total fecal bile acid output was decreased by 41%. Cafestol did not affect hepatic free and esterified cholesterol, but it decreased LDLR mRNA levels by 37%. The VLDL apoB and triglyceride production rates, as measured after Triton injection, were 2-fold decreased by cafestol, indicating that the number of particles secreted had declined and that there was no change in the amount of triglycerides present in the VLDL particle during cafestol treatment. However, the VLDL particles contained a 4-times higher amount of cholesteryl esters, resulting in a net 2-fold increased secretion of cholesteryl esters. The decrease in triglyceride production was the result of a reduction in hepatic triglyceride content by 52%. In conclusion, cafestol increases serum cholesterol levels in apoE*3-Leiden mice by suppression of the major regulatory enzymes in the bile acid synthesis pathways, leading to decreased LDLR mRNA levels and increased secretion of hepatic cholesterol esters. We suggest that suppression of bile acid synthesis may provide an explanation for the cholesterol-raising effect of cafestol in humans. (Arterioscler Thromb Vasc Biol. 2000;20:1551-1556.) Key Words: bile acid synthesis cholesterol 7-hydroxylase sterol 27-hydroxylase apolipoprotein E*3-Leiden mice cafestol U nfiltered coffee markedly increases serum cholesterol levels in humans. The compounds responsible for this effect are cafestol and kahweol, 2 diterpenes that are present in coffee beans. 1 From our experiments, cafestol appeared to be by far the more potent compound. 2 We estimated that each 10 mg of cafestol ingested per day raises serum cholesterol levels by 0.13 mmol/L. 3 In humans, 80% of the rise in total cholesterol is accounted for by LDL cholesterol, and the rest is due to a rise in VLDL cholesterol. 4 The mechanism by which coffee diterpenes influence lipid metabolism is largely unknown. Recently, we reported that cafestol suppressed bile acid synthesis in cultured rat hepa-tocytes by downregulation of cholesterol 7-hydroxylase and sterol 27-hydroxylase. 5 Suppression of bile acid synthesis will lead to an increased pool of regulatory cholesterol, resulting in decreased expression of the hepatic LDL receptor (LDLR). This may provide an explanation for the cholesterol raising effect of cafestol in humans. 5 The availability of an