688 



SCIENCE 



[N. S. Vol. XXIX. No. 745 



dance of protein it may be preparing as mucii 

 creatin as is needed for the maintenance of its 

 normal supply. Creatin given with the food 

 is consequently not retained by the muscles to 

 the same extent as when the food contains an 

 insufficient supply of protein. 



Widely quoted as these experiments have 

 been, they are scarcely conclusive on this point. 

 Van Hoogenhuyze and Verploegh ('08) have 

 lately maintained that the variations in the 

 daily nitrogen output are large enough to 

 exceed the quantities which Folin failed to 

 recover when creatin was fed with a low diet. 

 All feeding experiments are further compli- 

 cated by the difficulty of ascertaining whether 

 creatin is to any considerable extent destroyed 

 by bacteria in the alimentary tract and thus 

 escapes absorption as such. At present there 

 is no way of telling what became of the cre- 

 atin-N in the feeding experiments on record. 



If, as we have learned, ingested creatin fails 

 to increase appreciably the output of creatinin 

 in the urine, must we not admit that the cre- 

 atinin of the urine has an origin quite inde- 

 pendent of the creatin of the muscle ? " It 

 would be most remarkable," writes EHercker, 

 " if the endogenous creatin of the muscle were 

 changed into creatinin in the body, whereas 

 ingested creatin is not transformed in this 

 way." It is, however, no more remarkable 

 than the fact that ingested cystin may be 

 completely oxidized in patients who are at the 

 same time excreting the cystin which arises 

 in their intermediary protein metabolism. 



The recent investigations with the Folin 

 method have shown that neither increased nor 

 decreased muscular activity uncomplicated by 

 other factors has any effect upon the excretion 

 of creatinin (van Hoogenhuyze and Verploegh, 

 '05; Shaffer, '08). This fact of itself can not 

 speak against the origin of creatinin from 

 creatin so long as it is not known what part 

 creatin may play in the contraction of muscles. 

 Shaffer has calculated a " creatinin-coeffi- 

 cient," representing the milligrams of excreted 

 creatinin-N per kilogram of body weight, in 

 a large number of individuals. This " coef- 

 ficient " is regularly found low in individuals 

 with lowered muscular efficiency and shows a 

 parallelism with the muscular development 



and strength. He concludes that creatinin 

 is not an index of the total endogenous pro- 

 tein katabolism, but is probably derived from, 

 and an index of, some special process of the 

 normal metabolism taking place largely, if not 

 wholly, in the muscles. And upon the in- 

 tensity of the process appears to depend the 

 muscular efficiency of the individual. As a 

 theory of metabolism this statement affords us 

 little help; but as an expression of fact it 

 elucidates a variety of interesting conditions. 

 Thus the coefficient is found low in women, 

 who as a rule are less developed muscularly 

 than men; in infants with small bulk of mus- 

 cular tissue; in the feeble aged; and in pa- 

 tients convalescent from wasting disease. 



Creatin, not present in normal urines unless 

 creatin is taken as food, is found in the urine 

 during inanition and in certain pathological 

 states. In starvation the creatinin output has 

 been found to diminish gradually with the 

 progress of the inanition. This is true like- 

 wise of another endogenous product, uric acid. 

 The unique appearance of creatin under these 

 circumstances must be borne in mind wherever 

 this substance is found accompanying ab- 

 normal conditions attended by inadequate 

 nutrition. In every such case it is reason- 

 able to ascribe the source to the creatin of the 

 muscles. Creatin may be excreted in acute 

 fevers and various manifestations where there 

 is a rapid loss of muscle proteins. Large out- 

 puts have been found in the urine of women 

 during the first week post partum, when reso- 

 lution of the uterus is taking place (Murlin; 

 Shaffer). The fact that the creatinin elim- 

 ination bears no appreciable relation to creatin 

 in these conditions speaks further for the 

 biological independence of the compounds. 



There are numerous data already on record 

 in attempts to connect the liver and other 

 organs with the phases of metabolism which 

 we are considering. It is almost too early to 

 interpret these adequately because of the com- 

 plexity of factors involved (Mellanby, '07; 

 Spriggs, '07 ; van Hoogenhuyze and Verploegh, 

 '08). In many instances, especially in the 

 cases of hepatic disease, under-nutrition is an 

 ever-present complication. Other cases, such 

 as the muscular dystrophies with lowered ere- 



