Clinical and experimental studies on folic acid deficiency due to anticonvulsants. 2. Investigations on patients receiving anticonvulsants and experimental study on the effect of diphenylhydantoin on the absorption of folic acid in rats

A high incidence of subnormal serum folic acid levels was observed in 48 patients receiving anticonvulsants (75 %). In peripheral blood, macrocytosis was detected in 46 % and an increase of hypersegmented neutrophils was also seen in 24 % of the patients. Correlation existed between these signs and low serum folate levels. The growth response of Lactobacillus casei and L. leichmannii was not suppressed by the addition of various anticonvulsants to the medium of the bioassay systems. Administration of 5 mg of folic acid for a month corrected macrocytosis and an increase of hypersegmented neutrophils significantly. Folic acid supply also decreased mean diameters of the nuclei of oral epithelial cells significantly. It is concluded that subclinical folic acid deficiency is common among the patients receiving anticonvulsants. Absorption of 3H.folic acid from the small intestine of rats was inhibited by large dose of diphenylhydantoin (20 mg) not by 5 mg. This fact suggests that in patients on diphenylhydantoin, the quantity balance of folic acid and diphenylhydantoin in the intestine regulates the absorption of folic acid.