582 NIACIN 



the more of the supplements which were added, the more severe the appar- 

 ent nicotinic acid deficiency became. In most instances nicotinic acid and 

 tryptophan were equally effective in overcoming the growth depression 

 (within certain hmits). 



Most, if not all, of these observations can be explained according to the 

 concept of amino acid balance. When the diet contains more tryptophan, 

 in proportion to available amounts of other ammo acids, than is required 

 for protein synthesis and other anabolic demands, then a portion of the 

 tryptophan is converted into nicotinic acid in an efficient fashion. When, 

 however, the supply of tryptophan is restricted so that it is the most limit- 

 ing amino acid, then the tissues seem to metabolize it in a different fashion. 

 Its utilization becomes quite inefficient and very little nicotinic acid is 

 formed, as shown by Krehl and associates.^- The greater the deficit of 

 tryptophan in proportion to the other amino acids, the more severe the 

 nicotinic acid deficiency seems to be. If nicotinic acid is supphed in these 

 low-tryptophan rations, the tissues seem to be relieved of the necessity 

 for converting tryptophan to nicotinic acid and the metabolism of trypto- 

 phan becomes efficient once again; i.e., the added nicotinic acid seems to 

 "spare" tryptophan. 



This concept, if valid, implies that the metabolic channels into which an 

 amino acid can be directed may vary according to the needs of the tissues 

 for essential substances. It also implies that the metabolic utilization of an 

 amino acid may become quite inefficient when it is the most limiting amino 

 acid. Further, it is evident that the absolute requirement of an organism 

 for an amino acid varies not only with the relative supply of other amino 

 acids but with the dietary supply of essential substances which can, in case 

 of need, be made from the amino acid. 



The role of amino acid balance in nutrition has been reviewed by El- 

 vehjem and KrehP^ and by Krehl. "^ 



c. Influence of Carbohydrates 



Krehl and associates^ were the first to note that dextrin, starch, glucose, 

 and lactose had a nicotinic acid sparing action when compared to diets 

 containing sucrose in the rat. These findings have been confirmed and 

 extended.^' ^^' *^ A similar phenomenon may exist in the rabbit,"- ^^ al- 

 though the reverse apparently obtains in chicks; i.e., starch increases 

 nicotinic acid requirements. ^^ The explanation usually given these phenom- 

 ena is that different carbohydrates alter the intestinal flora and thereby 



62 W. A. Krehl, J. de la Huerga and C. A. Elvehjem, J. Nutrition 164, 551 (1946). 



63 C. A. Elvehjem and W. A. Krehl, J. Avi. Med. Assoc. 135, 279 (1947). 

 6^ W. A. Krehl, Vitamins and Hormones 7, 111 (1949). 



66 L. M. Henderson, T. Deodhar, W. A. Krehl, and C. A. Elvehjem, /. Biol. Chem. 

 170, 261 (1947). 



