504 VITAMIN Bi2 



trigeminal neuralgia have been reportedly benefited by the administration 

 of Bi2.^''^^ The favorable effect of B12 on the neurologic lesions of pernicious 

 anemia was undoubtedly a major factor in leading to its use in other ner- 

 vous system disorders. However, it should be pointed out that in these 

 conditions of obscure etiology and therapeutic refractoriness a great variety 

 of agents have temporarily enjoyed enthusiastic acceptance. The parenteral 

 doses of B12 for which effectiveness has been claimed have varied from 15 

 7 to as much as 1000 7. In general, relatively massive doses have been em- 

 ployed. Since amounts in the order of 1000 7 are far beyond the range of 

 dosage required for replacement therapy, any particular effect obtained 

 from them is probably attributable to a pharmacologic action rather than 

 to the supply of a deficient nutrient. 



It seems entirely possible that lack of B12 may be a component of complex 

 deficiency states associated with peripheral neuropathy. However, by anal- 

 ogy with pernicious anemia, it is difficult to explain the rarity of subacute 

 combined degeneration of the spinal cord in such nutritional disorders if 

 their neurologic manifestations are due in any large part to Bi2 deficiency. 

 The function of B12 in the maintenance of the integrity of the neurones is 

 not understood, and its therapeutic role in various neuropathies, other 

 than that associated with pernicious anemia, has not been clearly defined. 



9. Summary 



In summary, the major manifestation of B12 deficiency in man is ane- 

 mia characterized by an abnormal, or megaloblastic, type of erythro- 

 poiesis. Concurrently, alterations in leukopoiesis and thrombocyte pro- 

 duction occur. The hematologic changes associated with a lack of B12 are 

 identical with those observed in PGA deficiency states, and there is evidence 

 to indicate that the function of B12 in hemopoiesis is mediated through its 

 effect on the metabolism of PGA and related compounds. 



Vitamin B12, including some of its analogs, is identical with the extrinsic 

 factor of Castle. In pernicious anemia, deficiency of the vitamin results 

 from the aVjsence of Castle's intrinsic factor, which is secreted b}'^ the normal 

 stomach. Intrinsic factor may act by combining stoichiometrically with 

 B12 to form an unstable complex which protects the vitamin from utiliza- 

 tion by bacteria or its destruction in some other manner within the in- 

 testinal tract. An intrinsic factor present in the tissues may also function 

 in the normal metabolism of B12. Furthermore, there is evidence that in 

 pernicious anemia, as a result of Bio deficiency, toxic or inhibiting agents 



71 W. B. Bean, M. Franklin, and A. L. Salis, Am. J. Med. Set. 220, 431 (1050). 



72 S. M. Sancetta, P. R. Ayres, and R. W. Scott, Ann. Internal. Mai. 35, 1028 (1951). 

 " W. S. Fields and II. K. Hoff, Ncurolocjy 2, 131 (1952). 



7" W. S. Fields and II. E. Hoff, Merck Kept. October, 1952. 



76 J. Lereboullet and R. Pluvinage, J. Am. Med. Assoc. 148, 667 (1952). 



