500 VITAMIN Bi2 



not entirely responsible, for the therapeutic efficacy of parenterally ad- 

 ministered liver extracts in pernicious anemia. By implication at least, the 

 conclusion has been drawn that pernicious anemia is a B12 deficiency state, 

 induced by a gastric abnormality, and that whatever other nutritional 

 factors or toxic agents may be operative are either the direct result of lack 

 of B12 or, in any event, are counteracted completely by supplying B12 to 

 the tissues. The presence in liver of PGA, or more probably its formyl 

 derivative CF,^^ is, or course, well known and presumably accounts for the 

 efficacy of this material in PGA deficiency states, such as megaloblastic 

 anemia of pregnancy. The responses obtained in pernicious anemia to the 

 oral administration of whole liver or liver extracts may be attributable to 

 PGA, perhaps augmented by absorption of some of the B12 present in the 

 liver. It is also entirely possible that there are other as yet unidentified 

 hemopoietic factors in liver. In the manufacture of refined liver extracts of 

 high potency almost all the PGA compounds are eliminated in the process 

 of fractionation, and the therapeutic efficacy of such preparations can be 

 entirely accounted for on the basis of their B12 content.** 



Most clinical observers are in agreement that crystalline B12, or concen- 

 trates of the vitamin obtained from cultures of streptomyces (Str. griseus, 

 Str. aureofaciens) , are fully as effective as liver extracts in the treatment of 

 pernicious anemia, and, in fact, U. S. P. liver injection preparations are now 

 standardized by B12 assay rather than by clinical response tests. *^ The re- 

 port of Beard and associates^"' ^^ that B12 failed to maintain normal hema- 

 tologic values in approximately half of a group of twenty-seven patients after 

 5 to 10 months of treatment is probably explained, as suggested by the 

 authors, by the poor diets of the patients, particularly with respect to 

 sources of good-quality protein. The importance of animal protein in hemo- 

 poiesis and a correlation between macrocytic anemia and low intake of 

 protein of good biologic quality during pregnancy have been previously re- 

 ported.^- Other statements in the literature to the effect that B12 may not 

 correct all the hematologic values in pernicious anemia, even with the addi- 

 tion of PGA, are of interest but have not been confirmed, possibly because 

 of the highly specialized techniques employed by those who claimed to have 

 demonstrated them. Thus Larsen^^ reported that erythrocytes of normal 

 volume but increased diameter and lessened thickness are present in the 



"M. E. Swendseid, F. H. Bethell, and W. W. Ackerniann, J. Biol. Chem. 190, 791 



(1951). 

 « R. H. Girdwood, K. M. Carmichael, and B. Woolf, Brit. Med. J. II, 1357 (1950). 

 *^ U. S. Pharmacopeia, 14th revision, 3rd Supplement, 1951. 



" M. F. Beard, S. K. Mcllvanie, and M. Nataro, Southern Med. J. 43, 678 (1950). 

 '^ M. F. Beard and S. K. Mcllvanie, Proc. 3rd Intern. Congr. Haematol. Cambridge, 



England, 1950, Grune & Stratton, New York, p. 34, 1951. 

 " F. H. Bethell, E. Blecha, and J. H. Van Sant, J. Am. Dietet. Assoc. 19, 165 (1943). 

 " G. Larsen, Proc. 3rd Intern. Congr. Haematol. Cambridge, England, 1950, Grune 



& Stratton, New York, p. 25, 1951. 



