The Relationship of Tryptophane and Nicotinic Acid

Abstract

The name of Dr. Joseph Goldberger inevitably comes to mind in any discussion of the causation, prevention and cure of pellagra. He pioneered in the attempts to associate the appearance of the disease with causative nutritional factors; as he continued his studies he repeatedly showed the parallelism between presence or absence of pellagra and differences in the diet of the persons under examination. Particularly was the consumption of proteins of recognized superior biologic value regularly associated with the absence of the disease. In 1937 Elvehjem and his co-workers 1 demonstrated that nicotinic acid prevented and cured the canine analogue of human pellagra, and its efficacy in treating pellagra in man was promptly demonstrated.2 The earlier suggestion that protein of high nutritional value exerted a favorable effect on human pellagra and the discovery of the curative properties of nicotinic acid were partially harmonized by the observation that, in the rat, growth is retarded if corn grits are added to an experimental diet low in nicotinic acid and that either nicotinic acid or tryptophane brings about resumption of growth.3The foregoing observations suggest a more or less close relationship between protein and nicotinic acid in nutrition; indeed, hydrolyzed fibrin and gelatin both act like corn grits in retarding growth and glycine, and a mixture of amino acids simulating completely hydrolyzed casein will also have this effect.4 The influ¬ ence of corn grits in the diet has been ameliorated by use of dextrose or dextrin as a source of carbohydrate, which suggests that the metabolism of micro-organisms in the intestine may play a part in the phenomenon.5 Using the excretion of nicotinic acid and of N-methyl nicotinamide in the urine as a criterion, Rosen and co-workers 6 showed with this criterion that the same relationship exists between tryptophane and nicotinic acid. Later it was shown that human beings behave like laboratory animals with respect to a diminished output of the metabolites of nicotinic acid when a deficiency of nicotinic acid exists and its correction with tryptophane.7 On this basis, an amino acid imbal¬ ance produced by the administration of phenylalanine or threonine to rats gave evidence of interference with nicotinic acid-tryptophane metabolism, and the intra¬ venous route was as effective as the oral.8The rat is ordinarily able to synthesize enough nicotinic acid to maintain its physiologic well-being; however, when corn grits are added to a ration poor in nicotinic acid, the coenzyme content of liver, volun¬ tary muscle and brain is decreased.9 The vital part played by these enzymes in tissue oxidation suggests the gravity of the situation in which a widely used food can, through an amino acid imbalance from its protein of modest biologic value, cause this deep-seated alteration of usual physiologic chemical reactions. Fur¬ ther investigation of the interrelations of the known causative factors in the production of nicotinic acid deficiency is warranted by the considerable importance ...