The Metabolic Significance of Reduced Serum B₁₂ in Folate Deficiency

The depressed serum B₁₂ levels accompanying folate deficiency generally increase following folic acid therapy, and this phenomenon is cited as evidence that true B₁₂ deficiency did not preexist in such instances. In this study, the metabolic significance of reduced serum B₁₂ levels complicating folate deficiency was determined in bone marrow cultures by evaluation of abnormal incorporation of deoxyuridine into DNA-thymine, a defect characteristic of megaloblastic maturation due to folate or B₁₂ deficiency. In in vitro marrow cultures of seven patients with folate deficiency and normal serum B₁₂ levels, added B₁₂ resulted in no change in the depressed incorporation of deoxyuridine into DNA-thymine, with complete correction of the defect by added folate. However, in marrow cultures of five patients with folate deficiency and depressed serum B₁₂ levels, added B₁₂ produced a partial correction of the defective deoxyuridine incorporation, with complete correction by added folate. In vivo pharmacologic doses of B₁₂ in a patient with folate deficiency, but normal serum B₁₂ levels, resulted in no alteration in the degree of morphologic megaloblastic maturation or the abnormal deoxyuridine incorporation into DNA-thymine. In contrast, in a patient with both B₁₂ and folate deficiency, B₁₂ therapy resulted in partial correction of the abnormal deoxyuridine incorporation into DNA-thymine. with simultaneous reduction in the degree of morphologic megaloblastic maturation. However, abnormal deoxyuridine incorporation into thymine-DNA, consequent to folate deficiency, persisted. Similar findings were obtained in a patient with folate deficiency and associated reduced serum B₁₂. It is suggested that the depressed serum B₁₂ in patients with folate deficiency represents a true deficiency for hemopoietic tissue and contributes to the megaloblastic maturation by its effect on folate metabolism.