An Additional, Complementary Mechanism of Action for Folic Acid in the Treatment of Megaloblastic Anemia

Administration of supplemental folic acid addresses the impaired DNA synthesis causing megaloblastic anemia; however, despite the possibility of high doses of folic acid-5 to 15 milligrams (mg) daily for up to four months-the extremely rapid initial onset of action-30 to 60 minutes-when administered orally is not in keeping with the accepted mechanism, which can take up to nearly 22 hours, even under enzymatic control. This would suggest an additional, complementary non-enzymatic mechanism of nucleotide methylation at work; it is, therefore, proposed here, with in vitro evidence put forth, that rapid, non-enzymatic methylation by folic acid, via 5,10-methylenetetrahydrofolate and 7,8-tetrahydrofolate intermediates, of deoxyuridine monophosphate to form thymidylate using the cell membrane phospholipid phosphatidylcholine as a methyl donor, leaving de-methylated phosphatidylethanolamine, is a viable additional and complementary mechanism in helping reduce megaloblastic red blood cells to normal size and function.