Validity of animal models for the cholesterol-raising effects of coffee diterpenes in human subjects.

Cafestol and kahweol, coffee lipids present in unfiltered coffee brews, potently increase LDL-cholesterol concentration in human subjects. We searched for an animal species in which cafestol similarly increases LDL-cholesterol. Such an animal model could be used subsequently as a model to study the mechanism of action of cafestol and kahweol. Cafestol and kahweol increased serum lipids in African green monkeys (Cercopithecus aethiops), cebus (Cebus apella) and rhesus (Macaca mulatta) monkeys, hamsters, rats and gerbils differently from the increase in human subjects. In African green monkeys, the rise in total cholesterol was less pronounced than that in human subjects. In addition, the increase in total cholesterol was predominantly due to a rise in HDL-cholesterol rather than LDL-cholesterol. Thus, the rise in plasma lipids might illustrate the mechanism in these monkeys rather than the mechanism in human subjects. In other animal species, cafestol and kahweol did not raise cholesterol consistently. The variability in effects on serum lipids could not be explained by the mode of administration or dose of diterpenes, nor by the amount of cholesterol in the diet. In conclusion, we did not find an animal model in which cafestol and kahweol elevate plasma lipoproteins to the same extent as in human subjects. For the time being, therefore, studies on the mechanism of action should be done preferably in human subjects.