194 PTEROYLGLUTAMIC ACID 



6. Vitamin Bi2 plus ascorbic acid administered simultaneously intra- 

 muscularly effects a prompt correction of the megaloblastic marrow. 



7. Vitamin B12 given intramuscularly prophylactically does not prevent 

 characteristic development of the megaloblastic marrow. 



8. PGA given prophylactically prevents the development of the megalo- 

 blastic marrow on the vitamin-deficient diets even though scurvy and 

 anemia develop. 



9. Marked reduction in food intake alone leading to severe malnutrition 

 does not cause anemia or megaloblastic marrow. 



The role of vitamin B12 in the experimental anemia of monkeys just de- 

 scribed and in megaloblastic anemia of infancy seems secondary to that of 

 PGA. Pure vitamin B19 and liver extracts containing vitamin B12 but only 

 small amounts of PGxA. are sometimes able to completely cure megaloblastic 

 anemia in infants.^"'' Pteroylglutamic acid is almost always effective. In 

 the monkey vitamin B12 is ineffective in preventing the megaloblastosis, 

 but it is effective when given together with ascorbic acid. It should be borne 

 in mind that the diets contained milk and hence some PGA. Thus, the 

 vitamin B12 and ascorbic acid together may have increased the effective- 

 ness of the PGA in the basal diet used. 



The basal diets used by the Arkansas workers"^- to produce nutritional 

 cytopenia in the monkey contained orange juice. Liver extract was unable 

 to cure the macrocytic anemia in these experiments, which shows that 

 vitamin B12 in the presence of vitamin C is ineffective when no PGA is pres- 

 ent in the basal diet. The failure of May to observe megaloblastic anemia 

 on his milk diet supplemented with ascorbic acid, whereas Day observed 

 anemia on his cereal diet with orange, is undoubtedly due to the presence 

 of some PGA in the milk rations. Thus it appears that the PGA require- 

 ments of the monkey are increased by a deficiency of ascorbic acid. 



The most unique aspect of the scorbutically induced anemia in the mon- 

 key is its capacity to respond to small quantities of "folinic acid" (citro- 

 vorum factor). Fifteen micrograms of the factor per day in the form of 50 

 7 of concentrate produced the maximum hematological response, whereas 

 750 7 of PGA produced a suboptimal effect.'- The folinic acid produced a 

 prompt reticulocytosis followed by regeneration of the bone marrow to a 

 normal cellular pattern. Nichol and Welch^''^ have found that ascorbic acid 

 functions in the conversion of PGA to citrovorum factor. These data, to- 

 gether with observations on the high activit}^ of citrovorum factor in the 

 monkey, suggest that in the absence of adequate le^'cls of ascorbic acid the 



1"^ C. W. Woodruff, H. W. Ripy, J. C. Peterson, and VV. J. Darby, Feilialrics 4, 723 

 (1949), cited by C. D. May, E. N. Nelson, C. U. Lowe, and R. J. Salmon, Am. J. 

 Diseases Children 80, 191 (1950). 



i"5 C. A. Nichol and A. D. Welch, Proc. Soc. Exptl. Biol. Med. 74, 52 (1950). 



