Effect of Anticonvulsive Drugs on Folate Absorption and the Cerebrospinal Folate Pump

Effects of phenytoin on folate metabolism were studied in 94 subjects. Even healthy volunteers on diphenylhydantoin showed decreasing serum folates, but neurological disease other then epilepsy did not cause folate deficiency. In conjunction with earlier studies, this indicates that folate deficiency in epilepsy is caused by the drugs, rather than by the disease. Diphenylhydantoin as well as carbamazepine (Tegretolr̀) appear to be involved. No antimetabolite effect of diphenylhydantoin could be demonstrated in a microbiologic system, nor could any correlation be found between the serum concentrations of diphenylhydantoin and folates. Such a correlation would be expected in case of an antimetabolite action. Therefore, intestinal absorption was studied. No effect could be shown in man on the intestinal absorption of medicinal folates. The absorption of food folates, on the other hand, seemed to be inhibited. A cerobrospinal folate pump exists, which keeps the cerebrospinal folate concentration almost five times higher than that in the serum. This ratio was numerically but not significantly lower in the phenytoin‐treated patients.