X. EFFECTS OF DEFICIENCY 559 



nicotinic acid restriction is instituted and considerably before any symp- 

 toms of the deficiency become evident. This finding might be anticipated 

 from animal studies and in view of the fact that the tissues would undoubt- 

 edly attempt to conserve all available nicotinic acid if the supply were 

 limited, hence leaving little available for excretion. 



It should be mentioned that there are several published reports which 

 have failed to find any significant correlation between nicotinic acid intake 

 and excretion of nicotinic acid metabolites and hence are in seeming contra- 

 diction to the conclusions stated aboveJ^"^^ It is obvious, however, that if 

 the dietary circumstances are such that appreciable and undeterminable 

 amounts of nicotinic acid are synthesized from tryptophan, or possibly by 

 intestinal microorganisms or from any other source, then it would be almost 

 impossible to establish any correlation of intake to excretion or to the state 

 of nicotinic acid nourishment of the tissues. As pointed out by Ellinger 

 and Coulson^^ the urinary excretion of nicotinic acid derivatives is influ- 

 enced by the intake, the need in the body, the amount of methyl donors, 

 the efficiency of the methylating mechanisms, the amount of biosynthesis, 

 and other factors. 



Consequently, it is not surprising that most studies in which an attempt 

 has been made to determine nutritional status with respect to nicotinic 

 acid by determining the amount of urinary nicotinic acid derivatives have 

 encountered much variability and overlapping of results between normal 

 and presumably deficient groups. ''^■^^'' Studies in animals, where the dietary 

 and environmental circumstances can be controlled, have given much more 

 consistent results.^^- ^^' ^^ 



d. Load Tests 



Attempts have been made to increase the sensitivity and diagnostic use- 

 fulness of urinary excretion by employing the "load" principle. The theory 



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