Effects of vitamin A and ascorbic acid on in vitro cholesterol biosynthesis in the rat

In order to determine the effect of various doses of vitamin A and the interaction between vitamin A and ascorbic acid on cholesterol synthesis, male weanling rats were fed four levels of vitamin A as retinyl acetate (0, 20, 436 and 6,666 IU/g diet) and two levels of ascorbic acid (0 and 1 mg/g diet) for 28 days except the highest level of retinyl acetate which was fed for only 3 days. The incorporation of [2-14C]mevalonic acid into cholesterol intermediates, fatty acids and bile acids was determined in liver slices prepared from rats fed the above diets. The results may be summarized as follows: (a) ascorbic acid synthesis was reduced in both a deficiency and excess of vitamin A; (b) ascorbic acid in the diet prevented or blocked the decrease in liver ascorbic acid in vitamin A deficiency but not at the highest level of retinyl acetate (6,666 IU/g); (c) retinyl acetate inhibited the incorporation of [2-14C]mevalonic acid into cholesterol, lanosterol, dimethylallyl alcohol, geranol and farnesol, but had no inhibitory effect on the incorporation into squalene, nerolidol or bile acids, and (d) ascorbic acid had no inhibitory effect on cholesterol synthesis and no interaction between retinyl acetate and ascorbic acid was observed.