Subnormal Serum Folate and Macrocytosis Associated with Anticonvulsant Drug Therapy

Hematologic studies and microbiological assay of serum folate levels with L. casei and serum vitamin B₁₂ concentrations with L. leichmannii were performed on 60 subjects receiving anticonvulsant drug therapy and five epileptics receiving no treatment. Subnormal serum folate levels of less than 5.0 mµg./ml. were observed in 58 per cent of 53 subjects receiving Dilantin and one of seven patients on other anticonvulsant agents. The incidence of subnormal serum folate values was greater in those subjects who had been taking Dilantin for periods of time greater than 5 years, but did not appear to bear any correlation to the dosage of the drug. Slight or moderate macrocytosis was observed in 71 per cent of subjects receiving Dilantin who had subnormal serum folate levels and in 18 per cent of subjects with normal levels. Serum B₁₂ concentrations were within the normal range.

The growth of L. casei was not inhibited by anticonvulsant drugs when added to culture media containing folic acid or serum from patients on Dilantin with normal or low folate concentrations. Folic acid clearance studies were abnormally rapid in three of nine patients studied who were receiving Dilantin.

Possible sites of metabolic inhibition resulting in disturbances in folic acid metabolism during therapy with anticonvulsant medications are discussed.