Interrelations of vitamin B12 and folic acid metabolism: folic acid clearance studies.

The studies of many investigators have led to a unified concept of the megaloblastic anemias as a single morphologic entity due to defective nucleoprotein synthesis from various causes. The vast majority of patients with megaloblastic anemia have been found to have deficiency of vitamin B12, of folic acid, or of both vitamins. For this reason, the possible interrelations of these two vitamins have long piqued the curiosity of investigators (1, 2). Orally administered or injected pteroylglutamic acid (PGA) (folic acid) has been reported to disappear rapidly into the tissues of vitamin B12(leficient patients, as manifested by rapid disappearance of Streptococcus faecalis activity from serum and urine (3-6). 'The purpose of the present investigation was to determine whether the rapid disappearance of folic acid activity for S. faecalis from the serum of subjects with pernicious anemia reflects tissue depletion of folic acid, as believed by prior investigators, or instead indicates inadequate utilization of folic acid due to vitamin B12 deficiency. Prior results of part of these studies (7-10) suggest that the latter is the case. Incidental to these observations, the effect of intravenously administered PGA on serum vitamin B12 and on erythrocyte folic acid activity was determined. The studies here presented elaborate on our preliminary reports (7-10), indicating that folic acid activity "piles up" in human serum in the presence of vitamin B12 deficiency. The accumulation of this folic acid activity (probably N5methyl-tetrahydrofolic acid) provides direct evidence of deranged folic acid metabolism due to vitamin B12 deficiency. This folic acid-vitamin B12 interrelationship may explain much of the confu-