Mechanistic studies on the lipid-raising coffee diterpenes cafestol and kahweol in monkeys, mice and man

B. de Roos

Research output: Thesisinternal PhD, WU

Abstract

<p>Cafestol and kahweol are lipid-raising diterpenes present in unfiltered coffee. The objective of this thesis was to study their lipid-raising action in man. Unravelling this action might lead to new insights into the regulation of serum cholesterol levels.</p><p>We first studied the absorption and urinary excretion of cafestol and kahweol in eight ileostomy volunteers. About 70% of the consumed cafestol and kahweol was absorbed and thus available for raising serum lipids in humans. Only 1.2% of the diterpenes was subsequently excreted as a conjugate of glucuronic acid or sulphate in urine, suggestive for an extensive metabolism of coffee diterpenes.</p><p>We then searched for an animal model to study the mechanism of action of cafestol and kahweol. In African green monkeys, both diterpenes raised total cholesterol less pronounced than in man. Unlike humans, the rise in cholesterol was predominantly due to a rise in HDL cholesterol rather than LDL cholesterol. In apolipoprotein E*3-Leiden mice, cafestol and kahweol increased total cholesterol with 61% after eight weeks of treatment. The increase in total cholesterol was mainly due to a rise in VLDL and IDL cholesterol. After three weeks of treatment, total cholesterol was increased due to suppression of bile acid synthesis, which caused a decreased expression of the LDL receptor. In addition, VLDL became enriched in cholesteryl esters.</p><p>Two mechanistic studies were performed in healthy human subjects. Consumption of cafetiere (French-press) coffee increased CETP activity by 15% after 12 weeks of intervention. The increase in CETP activity clearly preceded the increase in LDL cholesterol. Cafestol increased serum triglycerides by an 80% increase in the production rate of VLDL <sub>1</sub> apolipoprotein B after two weeks of intervention. This resulted in an increased amount of VLDL <sub>1</sub> particles in the circulation. Cafestol did not change the composition of VLDL <sub>1</sub> . VLDL <sub>2</sub> became enriched with cholesteryl esters.</p><p>In conclusion, cafestol first increases plasma triglycerides by increasing the production rate of VLDL <sub>1</sub> apolipoprotein B. The subsequent rise in LDL cholesterol might be due to suppression of bile acid synthesis, which probably leads to down-regulation of the LDL receptor and/or to an enrichment of VLDL <sub>2</sub> with cholesteryl esters. The mechanisms of action that raise plasma cholesterol and plasma triglycerides in humans might be regulated independently in the liver.</p>
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
Supervisors/Advisors
  • Katan, M.B., Promotor
Award date14 Jan 2000
Place of PublicationS.l.
Print ISBNs9789058081728
Publication statusPublished - 2000

Keywords

  • coffee
  • cholesterol metabolism
  • cafestol
  • diterpenes
  • blood lipids

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