Absorption of physiologic doses of folic acid in subjects with topical sprue responding to tetracycline therapy.

T HE MEGALOBLASTIC ANEMIA which is characteristically present in persons with advanced tropical sprue is usually due to a combined deficiency of folate and vitamin B12.1 Deficiency of vitamin B12 in this condition has been clearly demonstrated to be secondary to malabsorption of this vitamin.’ The factors responsible for folate deficiency are less well-defined. Impaired absorption of pharmacologic doses of crystalline folic acid has been found present in from 44 to 100 per cent of groups of patients investigated27 and reduced absorption of smaller, 200 p.g. doses detected in from 35 to 47 per cent.6’81#{176} In the few studies in which serum folate determinations have been correlated with the results of absorption studies of crystalline folic acid, reduced absorption has been found present in some, but not all, subjects with folate 710 In 1961, Sheehy and his associates in Puerto Rico reported that treatment with physiologic doses of 25 p.g. crystalline folic acid resulted in a hematologic response in some individuals with tropical sprue who had had no previous response to dietary folate.” This observation led these investigators to propose that the absorption of a physiologic dosage of crystalline folic acid is unimpaired in some patients with tropical sprue and that folate deficiency in this circumstance is secondary to malabsorption of dietary polyglutamate forms of folate. Subsequent work has established the fact that therapy with oral tetracycline results in improvement in the intestinal lesion and in a remission of the megaloblastic anemia in some persons with tropical sprue.’246 The hematologic response in this circumstance appears to be related to folate repletion, since serum folate concentrations have been found to rise to within the normal range during tetracycline therapy in some persons,’4’15 whereas serum vitamin B12 concentrations remain consistently depressed.12”4’15 The physiologic mechanisms responsible for folate repletion during tetracycline therapy are unknown. Two alternatives suggest themselves: 1) That tetracycline directly improves the mucosal lesion with resultant improvement in the absorptive capacity for crystalline folic acid. Such has been shown