Folic acid is reduced by dihydrofolate reductase
to form tetrahydrofolate. Tetrahydrofolate is important in one carbon
transfer reaction and essential in the methylation of deoxyuridylate to
thymidylate during DNA synthesis. This leads to megaloblastic anemia,
although the mechanism is poorly understood in nutritional diseases. Folic
acid deficiency is caused by dietary deficiency, impaired absorption, or
increased requirements. Nutritional deficiency is seen in the elderly,
alcoholics, premature infants, infants raised on goat's milk and in
hemodialysis, hyperalimentation, and gastrectomy patients. Impaired
absorption occurs in sprue, regional enteritis, after extensive small bowel
resections, in Whipple disease, and in leukemic infiltration of the
intestine. Increased requirements are seen in pregnancy and in diseases with
increased cell turnover, such as hemolytic anemia.