Drugs, toxins and dietary amino acids affecting vitamin B12 or folic acid absorption or utilization

Abstract

Absorption, transport or utilization of vitamin B12 or folic acid is reduced by a growing number of drugs, as well as by ethanol and certain dietary amino acids. In most cases this results in only slight vitamin B12 or folic acid deficiency, but overt megaloblastic anemia may occur when drug dose is high and prolonged, and particularly when associated with pre-treatment borderline or decreased vitamin stores. Patients treated for protracted periods with anticonvulsants frequently have borderline folate stores, perhaps related both to poor diet and anticonvulsant-induced malabsorption. Oral contraceptive agents have been reported to be associated with folic acid deficiency and megaloblastic anemia. Folic acid antagonists (FAA) include agents for cancer chemotherapy, immunosuppression, psoriasis, protozoacides and antibacterials. Comparison of short-term cultures of human bone marrow with similar cultures of pathogenic microorganisms or neoplastic cells can measure the relative effects of new or suspected FAA on folate-dependent steps in DNA synthesis in vitro and may make it possible to predict use in vivo. Vitamin B12 antagonists are just beginning to be studied in this way. Various drugs reduce intestinal absorption of folic acid or vitamin B12. Ethanol may interfere with folic acid and B12 metabolism by a variety of mechanisms, including production of intestinal malabsorption and interference with folate metabolism, and possibly may act as a hematologic toxin by mechanisms other than disturbance of vitamin B12 or folic acid metabolism. Methionine, homocysteine, serine and glycine are involved in the biochemical cycle whereby folate coenzymes interconvert; vitamin B12 and pyridoxine are also involved in this cycle, and thus all these agents indirectly function in DNA-thymine synthesis. Homocystinuria and hyperglycinemia are associated with hematologic abnormalities which may relate to disturbed vitamin B12 and folic acid metabolism. Vitamin B12 deficient megaloblastosis may be provoked or aggravated by methionine.