552 NIACIN 



reactions which are catalyzed by these coenzymes. The chemistry of the 

 reactions and the manner in which the coenzymes function are known. Yet 

 with all this precise information, it is still impossible to offer any compre- 

 hensive explanation for the origin of many of the characteristic pathological 

 manifestations of human nicotinic acid deficiency such as dermatitis, skin 

 sensitivity to solar radiation, glossitis, atrophy of tongue papillae, and 

 mental abnormalities. An extensive field, still largely unexplored, exists in 

 which the biochemical reactions catalyzed by these coenzymes must be 

 integrated into the normal physiology and biochemistry of the intact ani- 

 mal. This will be necessary before any real picture of the specific effects of 

 malfunction of the enzyme systems can be drawn. Such will be a difficult 

 task, but until it is done our explanations for the manifestations of nicotinic 

 acid deficiency will be mostly educated guesswork based on reasoning 

 rather than demonstrated facts. 



2, The Deficiency State 



Only two mammalian species, man and dog, develop nicotinic acid defi- 

 ciency states which are characteristic and which can be readily differen- 

 tiated by their external manifestations from other vitamin deficiencies and 

 other diseases. The four D's of pellagra in man, dermatitis, diarrhea, 

 delirium, and death, form a characteristic picture which is readily diagnosed 

 by an experienced clinician. Milder and atypical syndromes are frequently 

 observed. Many excellent clinical descriptions of pellagra have been pub- 

 lished and need not be repeated here.^° Pellagra has been produced experi- 

 mentally in man on two occasions. The original demonstration of the 

 nutritional etiology of pellagra by Goldberger and associates in 1915"'^^ is 

 a classic and well-known story in nutrition. Their work represented the 

 first experimental production of pellagra in man and clearly demonstrated 

 the role of diet in the origin and prevention of the disease. It is of more 

 than passing interest, in view of the recently demonstrated tryptophan- 

 nicotinic acid relationship, that Goldberger suspected that an amino acid 



1" T. D. Spies in Clinical Nutrition, p. 531. Paul B. Hoeber, New York, 1950. 



" J. Goldberger and G. A. Wheeler, Public Health Repts. (U. S.) 30, 3336 (1915). 



12 J. Goldberger, Public Health Repts. {U. S.) 31, 3159 (1916). 



13 J. Goldberger, C. H. Waring, and D. G. Willets, Public Health Repts. (U . S.) 30, 

 3117 (1915). 



" J. Goldberger and G. A. Wheeler, [/. S. Public Health Service Hyg. Lab. Bull. 120 



(1920). 

 1^ M. X. Sullivan and K. K. Jones, U. S. Public Health Service Hyg. Lab. Bull. 120, 



117-126 (1920). 

 16 J. Goldberger and W. F. Tanner, Public Health Repts. {U. S.) 39, 87 (1924). 

 " J. Goldberger, G. A. Wheeler, E. Sydenstricker, W. I. King, W. S. Bean, R. E. 



Dyer, J. D. Reichard, P. M. Stewart, M. C. Edmonds, R. E. Tarbett, D. Wiehl, 



and J. C. Goddard, U. S. Public Health Service Hyg. Lab. Bull. 153, (1929). 



