77 SPECIES DEPENDENCE OF THE HYPERCHOLESTEROLEMIC EFFECT OF DIETARY CASEIN

We have hypothesized that casein, a phosphorylated protein, binds to an intestinal calcium-phosphate (CaP.) sediment and thus inhibits the efflux of bile acids from the enterohepatic cycle (EHC); consequently serum cholesterol may increase. This hypothesis has been supported by in vitro studies, which showed that unconjugated and glycine-conjugated bile acids bind to insoluble CaPi. This binding is inhibited by casein but not by dephosphorylated casein. In vivo studies with rabbits showed that dietary casein immediately inhibited the fecal output of bile acids. This inhibition preceded casein-induced hypercholesterolemia, indicating a cause-and-effect relationship. When rabbits were fed dephosphorylated casein, none of these casein-specific effects was observed. This indicates that the hypercholesterolemic effect of casein is due to its phosphorylation state. In species (like rat and man) with a high activity of intestinal phosphatase and a significant taurine conjugation of bile acids, casein neither affects the EHC of bile acids nor the serum cholesterol concentration. Results indicate that in these species the mucosal enzyme alkaline phosphatase dephosphorylates dietary casein, thus preventing hypercholesterolemia.