366 ASCORBIC ACID 



from studies in adult scurvy and the megaloblastic anemia of infancy, 

 ascorbic acid deficiency probably contributes to the anemia also and, be- 

 cause of its relationship to the metabolism of folic acid, tends to make the 

 anemia slightly macrocytic. The type of anemia which one finds in a scor- 

 butic child depends upon which metabolic factor is most critically needed. 



The etiology of the megaloblastic anemia of infancy is related indirectly 

 in many cases to vitamin C deficiency. This type of anemia, first described 

 by Veeneklaas in 1941^^ and by Zuelzer and Ogden^^ in 1946, occurs most 

 commonly in infants fed dried milk formulas unsupplemented by foods 

 rich in vitamin C. It occurs at the same age that infantile scurvy is most 

 prevalent, and at least 25% of infants with megalobalstic anemia have 

 scurvy also. The infant loses its appetite, becomes weak and apathetic, and 

 anemia develops rapidly. It may be macrocytic; more commonly it is 

 normocytic and normochromic though it may be hypochromic. The mega- 

 lobasts and bizarre metamyelocytes in the bone marrow typical of a de- 

 ficiency of one of the erythrocyte maturation factors are frequently the 

 only distinctive diagnostic feature. The anemia does not respond to the 

 administration of ascorbic acid alone, and rather poorly if at all to the 

 administration of vitamin B12. It responds dramatically to folic acid medi- 

 cation. 



The probable relationship of this type of anemia to ascorbic acid de- 

 ficiency has been demonstrated by May and his coworkers^* by a series of 

 experiments on monkeys fed the same milk diets which infants with megalo- 

 blastic anemia had been eating. These diets were deficient in folic acid and 

 ascorbic acid. Megaloblastic anemia usually follows the appearance of 

 scorbutic lesions within a week or two. Either folic acid or ascorbic acid 

 supplements will prevent it, although when folic acid supplements alone 

 are given, scurvy and normocytic anemia occur. Folic acid treatment after 

 the anemia has occurred will rapidly convert the megaloblastic marrow to 

 a normoblastic one and induce reticulocytosis and an erythrocyte response. 

 Ascorbic acid administration alone cures the scurvy and induces reticulo- 

 cytosis and remission in the anemia, although normalization in the mar- 

 row does not occur as rapidly as after folic acid therapy. 



Vitamin Bi2 alone does not have any therapeutic effect, but in combina- 

 tion with ascorbic acid it is said to have as dramatic an effect as folic acid 

 on the megalol)lastosis and anemia. There is no clear-cut evidence, however, 

 that the improvement is not due to the ascorbic acid alone. Folinic acid 

 is reported to lie effective in smaller doses than folic acid."*^ 



4' G. M. H. Vooneklaas, Folia Hannatol. 65, 303 (1941). 



« W. W. Zuelzer and F. N. Ogdeii, Proc. Soc. Exptl. Biol. Med. 61, 176 (1946). 



^' C. D. May, K. N. Nelson, C. U. Lowe, and K. J. Salmon, .4w. ./. Di.-^rases Children 



80, 191 (1950). 

 *^C. D. May, R. D. Sundberg, and F. ISchaar, J. Lab. Clin. Med. 36, 963 (1950). 



