Effect of diphenylhydantoin on the bioavailability of citrus folate

Long term use of the drug diphenylhydantoin (DPH) has been associated with biochemical evidence of folic acid deficiency and rarely with megaloblastic anemia. The mechanism of this nutritional deficiency is uncertain but is thought to result from DPH-induced alteration in the intestinal absorption of conjugated and/or free dietary folate. The effect of DPH on the intestinal absorption of free folates from a food source has heretofore not been reported. In this study triple lumen tube perfusion of the human jejunum was used to quantitate folate absorption from a control solution of orange juice and from an identical solution containing DPH. The results in eleven volunteers serving as their own controls indicate no effectof DPH at a concentration of 20 microgram/ml on folate absorption from this food source. The predominant form of folate in orange juice as determined by differential microbiologic assay is N-5-methyltetrahydrofolate. DPH does not appear to interfere with the absorption of free food folate which is both methylated and reduced.