INTERRELATIONS OF VITAMIN B12 AND FOLIC ACID METABOLISM: FOLIC ACID CLEARANCE STUDIES*

Abstract

In slightly to severely anemic vitamin Bl2-deficient subjects, after the intravenous injection of 15 [mu]g pteroylglutamic acid (PGA)per kg of body weight, folic acid activity for S. faecalis disappears rapidly but activity for L. casei disappears slowly from the serum. Markedly elevated serum folic acid activity for L. casei (25 or more m [mu]g per ml) was observed in 17 of 100 consecutive subjects with vitamin B12 deficiency. During specific therapy with daily doses of 5 to 1,000 [mu]g of vitamin B12, serum folic acid activity for L. casei may fall sharply and may reach levels below normal before rising again into the normal range. The phenomenon may be due to release of the block in utilization of L. casei folic acid activity caused by lack of vitamin B12, with subsequent rapid utilization in hematopoiesis, and may be similar to the fall in serum iron during therapy. Serum folic acid activity for L. casei may fall more slowly during specific therapy with smaller (1 [mu]g) daily doses of vitamin B12. These findings suggest that in the vitamin B12-deficient subject, PGA is rapidly converted to an L. casei-active and presumably metabolically useful form (probably N5- methyl-tetrahydro-folic acid) which then "piles up" in the serum because vitamin B12 is required for its normal utilization. This "piled up" folate activity would tend to reduce the amount of folic acid available for other 1-carbon unit transfers. These studies, by providing evidence for the concept that vitamin B12 is required for normal folic acid metabolism, support the possibility that the apparent folic acid deficiency in many patients with vitamin B12 deficiency may be in large measure due to secondarily deranged folic acid metabolism.