Harmful effect of megadoses of vitamins: electroencephalogram abnormalities and seizures induced by intravenous folate in drug-treated epileptics

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Abstract
Folic acid was administered intravenously during constant EEG monitoring to eight epileptic subjects who had received diphenylhydantoin therapy for more than 1 year. Six of the subjects displayed low folate levels by Lactobacillus casei assay in plasma and/or whole blood. Six patients received 75 mg of folate intravenously over a 30-min period without clinical effect of EEG change. One patient exhibited an increase in spike discharges on the EEG in comparison to the baseline pattern, but no clinical change or seizure while receiveing 150 mg of folate in a 30-min period. One patient displayed a 2-sec burst of spike and slow wave activity on the EEG after receiveing 7.2 mg of folate in a 3-min period. A tonic-clonic seizure occured after the infusion of 14.4 mg of folate, and again after infusion of 19.2 mg of folate. There appear to be wide variation in the ability of drug-treated epileptic subjects to tolerate infusions of folic acid. These variations help explain conflicting reports in the literature concerning the effect of folic acid administration on seizure control. Megadoses of folic acid should be employed with great caution in all subjects, but particularly among epileptics. Information is lacking as to whether folate might induce seizures in certain ostensibly normal individuals. It is postulated that folic acid exerts a direct effect among sensitive subjects on existing pathways concerned with the metabolism of folate, histidine, or other important brain metabolites. The mechanism of the anticonvulsant action of diphenylhdantoin remains unknown, but there is considerable evidence to suggest that it interferes with the deamination of histidine.