Changes of tissue creatine concentrations upon oral supplementation of creatine-monohydrate in various animal species

Creatine is a nutritional supplement with major application as ergogenic an d neuroprotective substrate. Varying supplementation protocols differing in dosage and duration have been applied but systematic studies of total crea tine (creatine and phosphocreatine) content in the various organs of intere st are lacking. We investigated changes of total creatine concentrations in brain, muscle, heart, kidney, liver, lung and venous/portal plasma of guin ea pigs, mice and rats in response to 2-8 weeks oral creatine-monohydrate s upplementation (1.3-2g/kg/d; 1.4-2.8% of dietary intake). Analysis of creat ine and phosphocreatine content was pet-formed by high performance liquid c hromatography. Total creatine was determined as the sum of creatine and pho sphocreatine. Presupplementation total creatine concentrations were high in brain, skeletal and heart muscle (10-22 mu mol/g wet weight), and low in l iver, kidney and lung (5-8 mu mol/g wet weight). During creatine supplement ation, the relative increase of total creatine was low (15-55% of presupple mentation values) in organs with high presupplementation concentrations, an d high (260-500% of presupplementation values) in organs with low presupple mentation concentrations. The increase of total creatine concentrations was most pronounced after 4 weeks of supplementation. In muscle, brain, kidney and lungs, an additional increase (p<0.01) was observed between 2-4 and 2- 8 weeks of supplementation. Absolute concentrations of phosphocreatine incr eased, but there was no increase of the relative (percentual) proportion of phosphocreatine (14-45%) during supplementation. Statistical comparison of total creatine concentrations across the species revealed no systematicall y differences in organ distribution and in time points of supplementation. Results suggest that in organs with low presupplementation creatine levels (liver, kidney), a major determinant of creatine uptake is an extra-intrace llular concentration gradient. In organs with high presupplementation total creatine levels like brain, skeletal and heart muscle, the maximum capacit y of creatine accumulation is low compared to other organs. A supplementati on period of 2 to 4 weeks is necessary for significant augmentation of the creatine pool in these organs. (C) 2001 Elsevier Science Inc. All rights re served.