ROLE OF ASCORBIC-ACID IN REGULATION OF CHOLESTEROL-METABOLISM AND IN PATHOGENESIS OF ATHEROSCLEROSIS

Chronic latent vitamin C deficiency may lead to hypercholesterolemia and the accumulation of cholesterol in certain tissues. Ascorbic acid supplementation of the diet of hypercholesterolemic humans and animals generally results in a significant reduction in plasma cholesterol concentration. Most studies relating ascorbic acid to atherosclerosis have used the rabbit as a model; but those studying the role of ascorbic acid in the regulation of cholesterol metabolism have generally used the guinea pig. A significant advance was the development of a model of chronic latent scurvy in the guinea pig. Chronic dietary inadequacy of vitamin C may influence the pathogenesis of atherosclerosis since it affects plasma cholesterol and triglyceride concentrations and vascular wall integrity. Ascorbic acid is involved in the regulation of cholesterol metabolism in several ways. Vitamin C deficiency is associated indirectly with a lowering of cholesterol absorption, this effect resulting from a reduction in the availability of bile acids, monoglycerides and fatty acids. The excretion of cholesterol as neutral steroids seems to be unaffected by ascorbic acid. Although much of the evidence for the involvement of ascorbic acid in cholesterol synthesis is equivocal, it seems likely that cholesterol synthesis may be decreased in vitamin C deficiency. Studies using guinea pigs with chronic latent vitamin C deficiency provided clear evidence that bile acid synthesis is reduced in this condition. This may result from a decrease in the activity of the microsomal enzyme cholesterol 7.alpha.-hydroxylase. The mitochondrial reactions of bile acid synthesis may require ascorbic acid. The role of ascrobic acid in the regulation of steroidogenesis appears to involve selective inhibitory and stimulatory effects on the desmolase, hydroxylase and dehydrogenase reactions which lead to the formation of pregnenolone and its subsequent conversion to steroid hormones.