Abstract
Substitution of casein for soybean protein in the diet causes high degrees of hypercholesterolemia in rabbits. When rats or humans were fed exactly the same diets, no response of the concentration of serum cholesterol to the type of protein was observed. The hypothesis is put forward that, in rabbits, dietary casein and peptides derived from it—because of their high degree of phosphorylation—inhibit the binding of glycine‐conjugated bile acids to insoluble calcium phosphate in the intestinal lumen. As a result, feeding of casein causes an increase in the availability of bile acids, which leads to enhanced absorption of bile acids and cholesterol. Eventually, the concentration of serum cholesterol will be increased. In rabbits this cascade of events occurs because these animals have a relatively low activity of intestinal alkaline phosphatase, and a high ratio of glycine to taurine in conjugated bile acids. Unlike glycine conjugates, taurine‐conjugated bile acids do not effectively bind to the intestinal calcium‐phosphate sediment. The low activity of intestinal alkaline phosphatase in rabbits secures the high degree of phosphorylation of casein and its peptide products in the small intestine. In contrast with rabbits, rats and humans have high activities of intestinal alkaline phosphatase and a low glycine‐to‐taurine ratio in conjugated bile acids. Thus the hypothesis presented would explain why rabbits, but not rats and humans, are susceptible to dietary casein with respect to the concentration of serum cholesterol. The relevance of the hypothesis as to the mechanisms underlying the hypercholesterolemic effect of some other dietary proteins is discussed.