Coffee Oil Consumption Increases Plasma Levels of 7alpha-Hydroxy-4-cholesten-3-one in Humans

Unfiltered coffee brews such as French press and espresso contain a lipid from coffee beans named cafestol that raises serum cholesterol in humans. Cafestol decreases the expression and activity of cholesterol 7-hydroxylase, the rate-limiting enzyme in the classical pathway of bile acid synthesis, in cultured rat hepatocytes and livers of APOE3Leiden mice. Inhibition of bile acid synthesis has been suggested to be responsible for the cholesterol-raising effect of cafestol. Therefore, we assessed whether cafestol decreases the activity of cholesterol 7-hydroxylase in humans. Because liver biopsies were not feasible, we measured plasma levels of 7-hydroxy-4-cholesten-3-one, a marker for the activity of cholesterol 7-hydroxylase in the liver. Plasma 7-hydroxy-4-cholesten-3-one was measured in 2 separate periods in which healthy volunteers consumed coffee oil containing cafestol (69 mg/d) for 5 wk. Plasma levels of 7-hydroxy-4-cholesten-3-one increased by 47 ± 13% (mean ± SEM, n = 38, P = 0.001) in the first period and by 23 ± 10% (n = 31, P = 0.03) in the second treatment period. Serum cholesterol was raised by 23 ± 2% (P <0.001) in the first period and by 18 ± 2% (P <0.001) in the second period. We corrected individual 7-hydroxy-4-cholesten-3-one levels for serum cholesterol levels, because coffee oil increases serum cholesterol and 7-hydroxy-4-cholesten-3-one is probably present in the lipoprotein fraction of serum. After correction, the increase in 7-hydroxy-4-cholesten-3-one was 24 ± 11% (P = 0.04) in the first period and there was no effect in period 2. Our study showed that coffee oil did not decrease, and actually increased, plasma levels of 7-hydroxy-4-cholesten-3-one in humans in 2 separate treatment periods. Therefore, this study does not support the hypothesis that cafestol decreases bile acid synthesis in human