560 NIACIN 



of this test is simple. If an organism is suffering from nicotinic acid defi- 

 ciency, its tissues are depleted of the vitamin and urinary excretion should 

 be low. A standard dose of nicotinic acid (usually as the amide) should 

 then go principally to replete the tissue stores; less should be excreted in 

 the urine than when the same amount is given to individuals whose tissues 

 are already normally saturated with the vitamin. This test undoubtedly 

 has some usefulness, but interpretation of individual tests is often difficult. 

 It has been useful as a research tool.^^' ^^' '^'^^ '^^' ^^- ^^- ^^-^''^ Doses of 50 to 

 500 mg. of nicotinamide and urine collection periods of 2 to 24 hours have 

 been recommended. There seems to be no agreement on any "standard" 

 technique for doing the test. 



5. Stomach 



About 60% of pellagrins have histamine-resistant achlorhydria.^^- ^^ A 

 return of normal gastric secretion frequently follows therapy with nico- 

 tinamide. It is of interest that one of the human subjects in whom Gold- 

 smith and associates'^ induced pellagra developed a histamine-resistant 

 achlorhydria with return of acid secretion following therapy. Another pa- 

 tient developed a slight reduction in gastric acidity. It has also been re- 

 ported that swine on a Goldberger type of blacktongue-producing diet 

 develop achlorhydria, although nicotinic acid-deficient dogs*^ and rats^'' 

 show essentially normal gastric secretion. It is also well known that nico- 

 tinic acid and the amide are capable of stimulating gastric secretion in 

 normal individuals as well as in patients with pellagra (p. 575). The acid- 

 secreting (oxyntic) cells of the stomach are known to have a very high 

 concentration of coenzyme I (DPN) (see Table VII). 



These facts have led to considerable speculation that DPN and TPN 

 may play a vital role in the mechanism by which gastric hydrochloric acid 

 is secreted. Patterson and Stetten^' have evolved a theory, and supported 

 it with some experimental evidence, that DPN is an essential component 

 of a stratified sequence of enzyme systems which transport the hydrogen 

 necessary for gastric hydrochloric acid production. Hawk and Hundley^" 

 were unable to obtain supporting evidence in nicotinic acid-deficient rats, 

 but these experiments certainly do not rule out the possibility of such a 

 mechanism. 



86 H. P. Sarett and G. A. Goldsmith, /. Biol. Chem. 167, 293 (1947); 177, 461 (1949); 



182, 679 (1950). 

 8' W. A. Perlzweig, E. D. Levy, and H. P. Sarett, /. Biol. Chem. 136, 729 (1940). 

 "^ D. Melnick, W. D. Robinson, and H. Field, Jr., J. Biol. Chem. 136, 145 (1940). 

 s^b p. Ellinger and R. Benesch, Lancet II, 197 (1945). 



88 V. P. Sydenstricker and E. S. Armstrong, Arch. Internal Med. 59, 883 (1937). 

 8s J. A. Layne and J. B. Carey, Gastroenterology 2, 133 (1944). 



90 E. A. Hawk and J. M. Hundley, Proc. Sac. Exptl. Biol. Med. 78, 318 (1951). 



91 W. B. Patterson and D. Stetten, Jr., Science 109, 256 (1949). 



