Homocysteinemia in rats induced by folic acid deficiency

The effect of folate deficiency on homocysteine metabolism was examined in rats given a folate-deficient diet. Total homocysteine was determined in serum stored at -22 degrees C for 3 wk. All animals in the control group had more than 20 ng.ml-1 of serum folate and more than 1000 pg.ml-1 of serum cyanocobalamin throughout the experimental period. In contrast, serum folate in animals given the folate-deficient diet decreased to less than 3 ng.ml-1 after 4 wk and to less than 2 ng.ml-1 (a subnormal level) after 10 wk of the experiment while serum cyanocobalamin remained at more than 1000 pg.ml-1 throughout the experiment. In the control group, mean serum total homocysteine +/- SD was 4.04 +/- 1.07 nmol.ml-1 during the 20 wk of experiment. At the 10th wk before serum folate reached subnormal levels, the animals given the folate-deficient diet had a mean serum total homocysteine of 7.67 +/- 1.53 nmol.ml-1, demonstrating a significant increase (P less than 0.001). No further significant increase of mean serum total homocysteine concentrations was observed after serum folate became subnormal. This study demonstrated for the first time that a selective deficiency of folic acid caused a 2-4 fold increase in serum total homocysteine when serum folate was at low normal and at subnormal levels in rats.