The activity of the
cholesterol 7 alpha-hydroxylating system containing cyto-chrome P-450 is depressed in the liver of guinea-pigs with chronic marginal
vitamin C deficiency. Slowing-down of this rate-limiting reaction of
cholesterol transformation to
bile acids causes
cholesterol accumulation in the liver, blood plasma and arteries, increase in the index total:
HDL cholesterol, prolongation of plasma
cholesterol half-life, increase in the index
cholesterol:
bile acids in the gall-bladder bile,
cholesterol gallstone formation and atheromatous changes on coronary arteries in guinea-pigs with long-lasting marginal
vitamin C deficiency. The most effective means for preventing these changes are
vitamin C doses ensuring maximal steady-state levels of ascorbate in the tissues. In most of hypercholesterolemic persons with a low
vitamin C status, the administration of
ascorbic acid in doses 500-1000 mg per day lowers total
cholesterol concentration in blood plasma. This effect may be reinforced through a simultaneous administration of
bile acids sequestrants, such as
cholestyramine or
pectin. In every form of
hypercholesterolemia therapy (dietary and/or pharmacological), an adequate
vitamin C supply should be ensured in doses capable of creating maximal steady-state levels of ascorbate in human tissues.