Drug-nutrient interactions of folate
Several folate antimetabolites are used clinically, as cancer chemotherapy (e.g., methotrexate), and as antibacterial (trimethoprim) and antimalarial (pyri-methamine) agents. Drugs such as trimethoprim and pyrimethamine act by inhibiting dihydrofolate reduc-tase, and they owe their clinical usefulness to a con-siderably higher affinity for the dihydrofolate reduc-tase of the target organism than the human enzyme; nevertheless, prolonged use can result in folate deficiency.
A number of anticonvulsants used in the treatment of epilepsy, including diphenylhydantoin (phenytoin), and sometimes phenobarbital and primidone, can also cause folate deficiency. Although overt megalo-blastic anemia affects only some 0.75% of treated epileptics, there is some degree of macrocytosis in 40%. The megaloblastosis responds to folic acid sup-plements, but in about 50% of such patients treated with relatively high supplements for 1–3 years there is an increase in the frequency of epileptic attacks.