IX. EFFECTS OF DEFICIENCY IN HUMAN BEINGS 307 



Very low levels of folic acid uiul folinic acid are found in the livers of 

 the deficient monkeys.''^ The degree of megalol)lastosis is proportional to 

 the folinic acid depletion, and those agents which increase the folinic acid 

 level in the liver reverse megaloblastic marrows to normoblastic ones. Folic 

 acid, ascorbic acid, and folic acitl conjugate (parenteral) have this property. 



In early publications. May and his coworkers felt that ascorbic acid 

 deficiency interferes with the metabolism of folic acid compounds and, 

 in animals on reduced folic acid intake, causes severe deficiency of meta- 

 bolicallj^ active folic acid compounds. The scurvy seems to add a conditioned 

 deficiency of folic acid to a dietary deficiency of this substance. This theory 

 is strengthened by the importance of ascorbic acid to the conversion of 

 folic acid to folinic acid in liver slices, as pointed out by Nichol and Welch,^^ 

 and the greater therapeutic efficiency of folinic acid as compared to folic 

 acid in this monkey anemia.^"* Furthermore the fact that deficiencies of 

 both folic acid and ascorbic acid in guinea pigs, monkeys, and infants 

 induce the same abnormality in tyrosine and phenylalanine metabolism 

 is additional evidence favoring this theory and emphasizing the close 

 chemical relationship of these two compounds. In ascorbic acid-deficient 

 infants, this abnormality in metabolism and excretion is rapidly rectified 

 by ascorbic acid and to some extent by large doses of folic acid. 



However, May and his associates believe now that ascorbic acid de- 

 ficiency merely acts as a "stress factor," possibly through the pituitary- 

 adrenal axis, which places a greater demand on folic acid metabolism than 

 usual .''^ They can find no direct evidence from the folinic acid levels in the 

 livers of their animals that ascorbic acid deficiency interferes with the con- 

 version of folic acid conjugates or folic acid to folinic acid. They conclude 

 that ascorbic acid is not essential for the normal metabolism of folic acid 

 compounds. This more recent theory does not explain the increased levels 

 of folinic acid in the livers of the monkeys treated with ascorbic acid, nor 

 the better response of these animals to folinic acid than to folic acid. It is 

 evident that this chapter is not yet complete. The inference is strong, 

 however, that many cases of megaloblastic anemia in infancy are analogous 

 to this monkey anemia. 



In adult persons also, ascorbic acid deficiency provokes many mechanisms 

 through which anemia may occur.^^- "-^^ There may be external blood loss 



« C. D. May, A. Hamilton, and C. T. Stewart, Blood 7, 978 (1952). 



« C. A. Nichol and A. D. Welch, Proc. Soc. Expt. Biol. Med. 74, 52 (1950). 



« S. R. Mettier, G. R. Minot, and W. C. Townsend, J. Am. Med. Assoc. 95, 1089 



(1930). 

 *' R. B. McMillan and J. C. Inglis, Brit. Med. J. 2, 233 (1944). 

 «B. Gottlieb, Brit. Med. J. 2, 119 (1945). 



" H. F. Dunlop and H. Scarborough, Edinburgh Med. J. 42, 47G (1935). 

 " L. J. Wade, E. W. Czebrinski, and G. Wood, J. Missouri State Med. Assoc. 43, 



756 (1946). 



