18 THE PROTEIN ELEMENT IN NUTRITION 



in the muscles, and upon the intensity of this process appears to 

 depend the muscular efficiency of the individual. 



Still more recently Levene and Kristeller undertook a series 

 of investigations as to the role of the muscular system in regulating 

 the creatinine output. Observations were made on twenty-four 

 patients affected with disease in which the muscular system was 

 involved. The influence of diet was also studied whenever the 

 creatinine output was found abnormal. Three forms of diet were 

 generally employed : one of low protein content, but containing 

 sufficient calories, the nitrogen intake not exceeding 6 grammes, 

 and the calories reaching 3,000 per day ; the second diet of 

 approximately the same calorific value contained milk and eggs, 

 with a nitrogen content of about 10 grammes ; and the third, a 

 beef diet, with a nitrogen content of 20 grammes per day. In 

 health these diets should not markedly influence the creatinine 

 output. 



A review of the results brings to light the following facts : 

 In all pathological conditions involving the muscular system 

 the rate of katabolism of ingested creatine is lowered, and part 

 of the ingested substance is removed in the form of creatinine. 

 When there was dissolution of muscular tissue with diminution 

 of muscular activity, the output of creatinine was low and that 

 of creatine high. In some cases the output of both creatine and 

 creatinine was influenced by the protein content of the diet. 

 The findings cannot be interpreted adequately on the basis of any 

 one of the existing views on the mechanism of creatine metabo- 

 lism. Thus, Shaffer's hypothesis that the extent of creatinine 

 output is determined by muscular efficiency does not harmonize 

 with the observations on progressive muscular atrophy, where 

 there may be an extreme degree of muscular wasting, without 

 any marked alteration of the creatinine output. Folin's theory, 

 which regards the intensity of cellular katabolism as the principal 

 factor in influencing the creatinine output, is not supported by 

 these investigations. Mellanby's view, likewise, is not sufficient 

 to interpret the results obtained. These authors believe that in 

 the regulation of the creatinine output at least two factors are 

 concerned : the formation of the substance, very probably from 

 protein, and its further oxidation. Any disturbance of either 

 may lead to an abnormal output of creatinine. 



The constant value in the amount of the creatinine output in 

 normal individuals is explained as being due to a condition of 



