A group of epileptic patients with low serum and cerebrospinal fluid (CSF) folate levels were treated in a double-blind controlled study over a six-month period with replacement using folic acid (pteroylglutamic acid). No statistical change in seizure frequency or severity was detected and no improvement in psychological test performance was observed. Significant decreases in mean serum and CSF phenobarbital and diphenylhydantoin concentrations were found in the folic acid treated subjects. In spite of marked elevation of folate in serum, there was no apparent entry into the CSF. It is assumed that anticonvulsants interfere with conversion of folic acid to 5-methyltetrahydrofolate, a form which enters the CSF. Confirmation of this was obtained in a small group of patients treated with leucovorin in whom CSF fluid levels rose to seven times normal.
Mattson RH, Gallagher BB, Reynolds EH, Glass D. Folate Therapy in Epilepsy: A Controlled Study. Arch Neurol. 1973;29(2):78–81. doi:10.1001/archneur.1973.00490260022002
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