Creatine and creatinine metabolism in the normal male adult studied with the aid of isotopic nitrogen.

Experiments designed to demonstrate balance between the amount of creatine ingested and the amount retained or excreted as creatine and creatinine have so far failed in their purpose. The results of such studies have led to the opinion either that there is an end-product of creatine other than creatinine or that the synthesis of endogenous creatine is retarded by exogenous creatine (1). We have reinvestigated the question of creatine balance by means of isotope methods. By labeling the tissue creatine of a human subject with N15 it has been possible to observe the changes in the amount of creatine deposited in the body after the ingestion of non-isotopic creatine. At the same time, the relationship between the amount of creatine present in the tissues at any time and the amount excreted as creatinine has been studied. Finally, the rate of turnover of body creatine was measured before and after the administration of exogenous creatine. Bloch, Schoenheimer, and Rittenberg (2) have shown that the creatinine excreted in the urine of rats fed isotopic creatine while subsisting on a creatine-free diet must have been derived from body creatine, since the concentrations of N15 in the creatinine and the muscle creatine were identical. Experimental confirmation through the use of deuteriocreatine has been provided by du Vigneaud and his collaborators (3,4). In view of these observations we have used the isotope concentration of the creatinine isolated from the urine of the subject to calculate changes of body creatine.