Abstract
Some dietary studies have been carried out on the metabolism of cholesterol and bile acids, in an attempt to elucidate the roles of three nutrients, namely, polyunsaturated fats, ascorbic acid and iron, which are known to influence the incidence of hyperlipidaemia and atherosclerosis. The rate-limiting enzyme of bile acid biosynthesis, cholesterol 7alpha-hydroxylase, is a member of the mixed function oxidase group of enzymes, in which cytochrome P-450 acts as the terminal oxidase. Thus, the influence of these nutrients on some parameters of mixed function oxidase metabolism was also examined. The hypercholesterolaemia and atheroma, induced by feeding a diet containing 20% saturated fat to rabbits, was prevented by giving a 20% polyunsaturated fat diet. However, the mechanism of the observed hypocholesterolaemia was shown not to be due to the influence of the unsaturated fat on the activity of cholesterol 7alpha-hydroxylase. Ascorbic acid deficiency was shown to impair the metabolism of both cholesterol and foreign compounds in the guinea pig. However, there is apparently a critical threshold level of dietary intake required to permit normal metabolism,which shows an interindividual and inter-species variability. "Megadose" quantities of ascorbic acid did not appear to adversely affect cholesterol or foreign compound metabolism. The administration of an iron-deficient diet to rats was shown to influence serum cholesterol concentrations, at least partly by an effect on cholesterol 7alpha-hydroxylase activity; however the direction of this effect was not consistent. It is possible that the influence of dietary iron deficiency on cholesterol and foreign compound metabolism may be dependent on the relative depletion of iron stores and/or on an interaction with other trace minerals such as copper. Finally, a hypothesis has been proposed, which suggests that cytochrome P-450 may play a central role in the pathogenesis of atherosclerosis.