INTRODUCTION 17 



limited supply of protein in the food on the physical well-being 

 of the individual or of a race. 



Since the introduction of Folin's colorimetric method of 

 creatinine estimation, a great amount of research has been 

 carried out on its elimination under various conditions of diet 

 intake and energy output. Van Hoogenhuyze and Verploegh 

 made a large series of experiments to determine the effect of 

 exercise ; they arrived at the conclusion that muscular work 

 only produces an increased elimination of creatinine when the 

 body is forced to live at the cost of its own tissues, as in starva- 

 tion. Noel Paton and Dorner, later also Cathcart, found 

 a relation between the creatinine excreted and the intaken 

 protein. 



The most complete study of the subject, however, is by 

 E. Mellanby, and the conclusions he has arrived at are of con- 

 siderable importance in connection with the views expressed by 

 Folin and others. The broad general conclusions to which 

 Mellanby comes are, that in the formation of creatinine muscle 

 plays a small part, whilst the liver, on the other hand, is inti- 

 mately connected with the production of creatine and the 

 excretion of creatinine. 



He believes the liver to be continuously forming creatinine 

 from substances carried to it by the blood-stream from other 

 organs, that in the developing muscle this creatinine is changed 

 to creatine and stored, while after the muscle has reached a 

 saturation -point creatinine is continuously excreted. Mellanby 

 brings forward a considerable mass of evidence to support his 

 conclusions. The fact that in the chick creatinine is not excreted 

 until a week after hatching, which he shows by analyses to mean 

 that the muscles are not until then saturated with creatine ; 

 that there is almost complete absence of creatinine from the urine 

 of young children and also of puppies, lends added support to 

 his findings. 



Later, Shaffer, from a careful study of the excretion of creatine 

 and creatinine by normal and pathological subjects, arrives at 

 the conclusion that creatinine is not an index of total endogenous 

 protein katabolism. Subjects of exophthalmic goitre and others, 

 in whom the total endogenous katabolism is probably much 

 increased, excrete very little creatinine. He states that creatinine 

 is derived from, and its amount is an index of, some special 

 process of normal metabolism taking place largely, if not wholly, 



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