Homocysteinemia in rats induced by folic acid deficiency

Abstract

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°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<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.