Interrelationships of vitamin B12, folic acid, and iron in anemia of infancy and childhood: effect of vitamin B12 and iron therapy on folate metabolism

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Abstract
The interrelationship of vitamin B12, folic acid, and iron in 40 children from 6 months to 12 years of age have been studied. Vitamin B12 deficiency (serum B12 ≤ 140 pg/ml) was seen in 19 (48.7%) patients. Serum iron was less than 70 µg/100 ml in 36 (90%), and saturated transferrin was less than 15% in 31 (79.5%) patients. Serum folate was less than 3 ng/ml in eight, but red cell folate in the deficient range was seen in only two patients. High serum folate was associated with vitamin B12 deficiency, but concurrent severe iron deficiency appears to alter this relationship. Red cell folate in iron deficiency with or without concurrent lack of vitamin B12 was high, and upon iron repletion, it significantly fell. However, the red cell folate rose when vitamin B12 therapy was given; on both these occasions, the blood folate rose. It has been inferred that in severe iron deficiency, red cell affinity for folate (THF, methyl-THF) is high and leads to a greater uptake of folate by the newly forming red cells. This may not permit a greater accumulation of methyl-THF in plasma. The impaired generation of THF from methyl-THF seen in vitamin B12 deficiency, however, may not be affected. On repletion of iron, red cells release folate into the plasma. The folate is also released from stores (presumably from liver) with the administration of iron and vitamin B12, although the exact mechanism of its release is not known. Enhanced erythropoiesis may have a contributory role.