A large body of literature indicates that protein from soybeans reduces blood cholesterol concentrations in experimental animals as well as in humans. The mechanism and component of soy responsible has not been established fully. Some suggest that when soy protein is fed, cholesterol absorption and/or bile acid reabsorption is impaired. This is observed in some animal species, such as rabbits and rats, but not in humans nor when amino acids replace intact soy protein. Others propose that changes in endocrine status, such as alteration in insulin:glucagon ratio and thyroid hormone concentrations, are responsible. The metabolic changes that have been observed on soy protein feeding in a variety of animal models, and in some cases humans, include increased cholesterol synthesis, increased bile acid synthesis (or fecal bile acid excretion), increased apolipoprotein B or E receptor activity and decreased hepatic lipoprotein secretion and cholesterol content, which are associated with an increased clearance of cholesterol from the blood. One hypothesis suggests amino acid composition or proportionality of soy causes changes in cholesterol metabolism (possibly via the endocrine system). Others have proposed that nonprotein components (such as saponins, fiber, phytic acid, minerals and the isoflavones) associated with soy protein affect cholesterol metabolism either directly or indirectly.