Effective Absorption and Utilization of Oral Formyltetrahydrofolate in Man

Abstract

Reversal of the effects of antifolates requires effective expansion of the body pool of reduced folate coenzymes. In the past, this has required parenteral use of 5-formyltetrahydrofolate. By use of Radio-labeled 5-formyltetrahydrofolate, we showed that its oral administration also expands the body reduced folate pool. After oral administration of 5-formyl-¹⁴C-tetrahydrofolate-³H to fasting subjects, the labels appeared in the serum, peaking at 60 minutes. Chromatographic analysis showed that the labeled serum folate was principally the naturally occurring 5-methyltetrahydrofolate-³H. Close to 90 per cent of orally administered 5-formyltetrahydrofolate appeared to be absorbed. The most constant labeled urinary folate was found to be 10-formyltetrahydrofolate or 5, 10-methenyltetrahydrofolate. Renal excretion of labeled 5-formyltetrahydrofolate occurred at undetectable serum levels whereas renal excretion of labeled 5-methyltetrahydrofolate was proportional to its serum concentration.