title: Coffee oil consumption increases plasma levels of 7alpha-hydroxy-4-cholesten-3-one in humans.
abstract: 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 7alpha-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 7alpha-hydroxylase in humans. Because liver biopsies were not feasible, we measured plasma levels of 7alpha-hydroxy-4-cholesten-3-one, a marker for the activity of cholesterol 7alpha-hydroxylase in the liver. Plasma 7alpha-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 7alpha-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 7alpha-hydroxy-4-cholesten-3-one levels for serum cholesterol levels, because coffee oil increases serum cholesterol and 7alpha-hydroxy-4-cholesten-3-one is probably present in the lipoprotein fraction of serum. After correction, the increase in 7alpha-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 7alpha-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 humans.
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands. Mark.Boekschoten@wur.nl
authors.forename: Mark V
authors.initials: MV
authors.lastname: Boekschoten
authors.forename: Maaike K
authors.initials: MK
authors.lastname: Hofman
authors.forename: Rien
authors.initials: R
authors.lastname: Buytenhek
authors.forename: Evert G
authors.initials: EG
authors.lastname: Schouten
authors.forename: Hans M G
authors.initials: HM
authors.lastname: Princen
authors.forename: Martijn B
authors.initials: MB
authors.lastname: Katan
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D002783:Cholestenones / Q000097:blood*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics; D003069:Coffee; D004224:Diterpenes / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D010938:Plant Oils / Q000494:pharmacology*; D012016:Reference Values
chemical_list: D002783:Cholestenones; D003069:Coffee; D004224:Diterpenes; D008055:Lipids; D010938:Plant Oils; C002656:7 alpha-hydroxy-4-cholesten-3-one; C053400:cafestol; D002790:Cholesterol 7-alpha-Hydroxylase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase