NUTRITION 267 



are chiefly creatinine and neutral sulphur ; to a less extent, uric acid and ethereal 

 sulphates. The variable products are urea and inorganic sulphates, not creatinine 

 and probably not neutral sulphur. The former obviously represent some constant 

 form of metabolism always proceeding, to which Folin gave the name of tissue or 

 endogenous metabolism, and to the variable type, that is, to the proteins used for 

 de-amination and giving of energy, the name intermediate or exogenous metabolism. 

 This view has been generally accepted, although some minor points as to the 

 complete distinction of the particular products in each case have been taken 

 exception to. Folin himself admits that urea is probably an end product of both. 

 According to Cathcart (1912, p. 95), the output of creatinine is itself subject to 

 small changes when the protein ingested is altered. 



The practical interest and importance of the question rests on the fact that the 

 amount of nitrogen which it is absolutely necessary to take in the food, is, in 

 theory, limited to that required bo form new tissues or replace wear and tear ; 

 that is, the endogenous fraction. Now the nitrogenous food is the most costly 

 part of a diet, so that it is of some importance to know how far it can wisely be 

 reduced. The value of the nitrogen minimum is therefore a question requiring 

 discussion. 



Firstly, what is the excretion of nitrogen in starvation 1 This may be taken 

 as the index of the waste of tissues, with certain qualifications. But it will be 

 clear that, for our present purpose, what we want to know is the loss of nitrogen 

 when sufficient carbohydrate is supplied for energy purposes, nitrogen being absent 

 from the food. The tissue proteins begin to break down in complete starvation in 

 order to afford the energy demanded by certain organs of vital necessity, such as 

 the heart, so that the issue becomes confused. If a particular excretory product, 

 under normal diet, were definitely known to be a product of endogenous 

 metabolism and of this alone, it would be more satisfactory to determine the amount 

 of this substance excreted. We cannot, as yet, be quite certain as to the existence 

 of such a product, although, according to Cathcart (1909), creatine, a constituent 

 of muscle tissue, is such a product, present only in starvation, so that the study of 

 its excretion gives valuable information, to which reference will be made later. 

 Some doubts, however, have been thrown by Graham and Poulton (1913) on the 

 cogency of the method used to estimate creatine in the urine. According to these 

 workers, there is no satisfactory evidence of the presence of this substance in the 

 urine, under any circumstances. According to Cathcart and Orr (1914), however, 

 these results do not affect the conclusions drawn by Cathcart from his experiments. 

 But, in any case, there is, according to M'Collum (1911, 1), another index in the 

 output of creatinine, a product obtained from creatine by removal of water (see 

 below, page 270). This is a constant fraction of the total nitrogen eliminated after 

 a long-continued diet free from nitrogen. In the pig, the creatinine nitrogen is, 

 under these conditions, 18 '5 per cent, of the total nitrogen excreted. So that if 

 the creatinine nitrogen be multiplied by 5 -5, the total nitrogen resulting from 

 endogenous metabolism is obtained. This conclusion rests on the fact that 

 creatine or creatinine is a characteristic product of the breakdown of muscular 

 tissue. 



In a later paper M'Collum and Hoagland (1913) show that this conclusion requires certain 

 modifications, which must be taken into account in attempts to make use of it. There are, 

 they say, at least two types of endogenous protein metabolism, one which can be stimulated 

 to increased production of ammonia by feeding with mineral acids, or to hippuric acid 

 production by glycine, while the other, which is represented by creatinine, remains unaffected 

 by these agents. 



From Cathcart's experiments (1909) it appears that, in man, the total output 

 of nitrogen on a carbohydrate diet, free from nitrogen, is about 5 g. per day. 

 Now Voit had laid it down that the daily intake of protein should be 120 g., 

 equivalent to 18 g. of nitrogen. Chittenderi (1905) regards this as far too 

 much and was able to maintain nitrogen equilibrium on 6 g. of nitrogen (40 g. 

 of protein) in various classes of men engaged in different kinds of work. There 

 is no doubt that Voit's amount is considerably in excess of that taken by a 

 large number of men. For example, Hamill and Schryver (1906) determined 



