American Journal of Clinical Nutrition, Vol 12, 130-144, Copyright © 1963 by The American Society for Clinical Nutrition, Inc.

Interrelationships of Vitamin B₁₂, Folic Acid and Ascorbic Acid in the Megaloblastic Anemias

¹ From the Department of Internal Medicine, Division of Hematology, College of Medicine, University of Cincinnati, and the Cincinnati General Hospital, Cincinnati, Ohio

To summarize, combined deficiencies or errors in the metabolism of folic acid, vitamin B₁₂ and ascorbic acid are much more common than single deficiencies or uncomplicated metabolic errors. Still, it is reasonable to name the disease by the dominant deficiency or error in metabolism as we have done in the past. Each of these deficiencies, or all of them in combination, can result in the appearance of megaloblastic forms in the bone marrow and macrocytosis in the peripheral blood. We believe the usual defect responsible for a megaloblast is an abnormality in folic acid metabolism which reduces the amount or activity of the folic acid coenzymes. Deficiencies of vitamin B₁₂ and ascorbic acid adversely influence formation of these coenzymes and other substances essential for DNA production. These deficiencies impair the ability of cells to form DNA, probably because thymine deoxyribotide cannot be synthesized in sufficient amount. As a result, the nucleus remains young and division is delayed while protein and hemoglobin formation proceed and the cell grows large. These developments produce the megaloblast—a cell which, because of deficiencies of folic acid, vitamin B₁₂ or ascorbic acid, has a limited supply of DNA precursors.