Folic acid (pteroylglutamic acid) is a vitamin derived from many dietary sources. Folic acid is an important coenzyme for the transfer of single carbon units in purine and pyrimidine nucleotide synthesis and amino acid conversions. The site of absorption of dietary folate is the duodenum and upper jejunum. Deficiency of this enzyme results from inadequate intake (common among alcoholics and drug addicts), or increased requirement (pregnancy and hemolytic anemias), and results in a macrocytic anemia with oval-shaped macrocytes. The anemia of folate deficiency is identical to that caused by B12 deficiency; however, the neurologic damage associated with B12 deficiency is not present with folate deficiency. Other symptoms of folate deficiency include infertility, glossitis, stomatitis and intestinal malabsorption.

Associated lab abnormalities include the above-mentioned macrocytic anemia with a low reticulocyte index. Hyperbilirubinemia and an elevated serum LDH may be present. The diagnosis is firmly established by the presence of a low serum folate level. If the serum folate level is normal and folate deficiency is still suspected, a more sensitive test is the red blood cell folate level. Serum folate normalizes rapidly after dietary supplementation; however, red cell folate levels remain depressed for the life of the red blood cell.

When confusion exists between the diagnosis of folate or B12 deficiency anemia, measurement of serum or urinary homocysteine and methylmalonic acid levels may be helpful. B12 is essential for the conversion of homocysteine to methionine and for the conversion of methylmalonyl-CoA to succinyl-CoA. Folate is also necessary for the conversion of homocysteine to methionine but not for the conversion of methylmalonyl-CoA to succinyl-CoA. Therefore, an elevation in both homocysteine and methylmalonic acid is seen with B12 deficiency whereas folate deficiency results in an elevation of only homocysteine.

Folate deficiency may develop in patients on hemodialysis or in patients with chronic hemolytic states. Hemodialysis patients are prone to deficiency of this vitamin as folate is dialyzable. Therefore, patients on either hemodialysis or peritoneal dialysis should be on empiric folate replacement therapy as should patients prone to chronic hemolytic states.

Therapy for folate deficiency is oral replacement with folic acid 1 mg PO QD. Alcoholics sometimes require higher doses of replacement therapy with folic acid 5 mg PO QD.