ABSTRACT
Identification of folic acid as a cure for megaloblastic anemia occurred in 1945.5 Since then, folate deficiency is recognized as one of the most prevalent vitamin deficiencies common in all areas of the world. Deficiency results from inadequate intake, defective absorption, abnormal metabolism, or conditions such as drug therapy, leading to increased requirements.5 Marginal deficiency produces general symptoms including tiredness, irritability, and decreased appetite. Severe deficiency produces megaloblastic anemia or the production of large immature red blood cells. Other symptoms include abdominal pain, diarrhea, ulcers in the mouth and pharynx, skin changes, hair loss, and neurological disorders such as dementia and depression.5,6
Close relationships between folate and vitamin B12 deficiencies result from the involvement of the vitamins in DNA synthesis. Megaloblastic anemia produced by deficiencies of folate and vitamin B12 are characterized by abnormally large megaloblasts in the bone marrow and abnormally large red cells in the blood.6 Impaired DNA synthesis arises from decreased production of 5,10-methylene tetrahydrofolate (5,10-CH2H4 folate), which is required for the synthesis of deoxythymidine monophosphate nucleotide.7 Similarities in the megaloblastic anemias produced by deficiencies of vitamins require biochemical assessment for accurate diagnosis and differentiation of the causative vitamin. Plasma folate levels (5-CH3-H4 folate) rapidly fluctuate with recent intake; therefore, erythrocyte folate levels are considered a more reliable status index.6 Serum folate levels stabilize after a few weeks at about 7 nmol L−1 when subjects are on a folate-deficient diet,8 indicating acute status but not the level of tissue stores.6 Erythrocyte folate levels follow liver levels and reflect tissue stores. The Institute of Medicine, in consideration of Dietary Reference Intake (DRI) values for folate, used an erythrocyte level of <305 nmol L−1 as the indicator of inadequate status.9 An indirect clinical measure is the urinary excretion of formiminoglutamic acid (FIGLU).
