Effects of Creatine Supplementation on Body Composition and Renal Function. in Rats LARISSA GORAYB FERREIRA 1 , CASSIA DE TOLEDO BERGAMASCHI 2 , MARISE LAZARETTI-CASTRO 3 , and ITA P. HEILBERG' 'Nephrology Division, 2 Physiology Division, and 3 Endocrinology Division, Universidade Federal de Silo Paulo, Sio Paulo, BRAZIL ABSTRACT GORAYB FERREIRA, L., C. DE TOLEDO BERGAMASCHI, M. LAZARETTI-CASTRO, and I. P. HEILBERG. Effects of Creatine Supplementation on Body Composition and Renal Function in Rats. Med. Sci. Sports Exerc., Vol. 37, No. 9, pp. 1525-1529, 2005. Background: The aim of the present study was to evaluate the long-term effects of oral creatine supplementation on renal function and body composition (fat and lean mass) in an experimental model. Methods: Male Wistar rats were supplemented with creatine (2 g.kg- 1 of food) for 10 wk in combination with treadmill exercise, 12 mrmin-', 1 h'd-1 (CREAT+EX, N = 12) or not (CREAT, N = 10), and compared with exercised animals without creatine supplementation (EX, N = 7) and CONTROL animals, N = 7. Body composition and bone mineral density (BMD) were determined by dual x-ray absorptiometry and glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by inulin and pamraminohippurate clearance, respectively. Results: At the end of the study (post), CREAT+EX presented higher lean mass and lower fat mass than CREAT, EX or CONTROL (349.7 ± 19.7 vs 313.3 ± 20.3, 311.9 ± 30.8,312.4 ± 21.0 g and 5.7 ± 2.3 vs 10.0 ± 3.3, 9.8 ± 1.5, 10.0 ± 3.5%, P < 0.05, respectively). Post lean/fat mass ratio was higher than baseline only in CREAT+EX (18.9 ± 7.2 vs 8.6 ± 1.8,P < 0.05). Post BMD was significantly higher than baseline in all groups. GFR and RPF were lower in CREAT versus CONTROL (0.5 ± 0.1 vs 1.0 ± 0.1 and 1.5 ± 0.2 vs 2.4 ± 0.5 mL.min-1, P < 0.05, respectively). Conclusion: Creatine supplement in combination with exercise increased the proportion of lean mass more than EX or CREAT alone. The use of creatine alone induced an important and significant reduction of both RPF and GFR. Key Words: CREATINE, BODY COMPOSITION, LEAN MASS, RENAL FUNCTION reatine (Cr) or a-methyl guanidine-acetic acid is distributed throughout the body, with 95% of the pool being found in skeletal muscle and the remain- ing 5% in the brain, liver, kidney, and testes (17). The use of Cr supplement by professional and recre- ational athletes as a potential ergogenic agent has been based on the potential increase in intramuscular total crea- tine and phosphocreatine (PCr) (1,11,13), rendering the latter available for ATP rephosphorylation, thus leading to improved performance during repeated high-intensity exer- cise tasks (2,11,12). Typical training adaptations, including increases in body mass and fat-free or lean mass, are re- ported as being enhanced concurrent with Cr supplementa- tion (25). However, it is not yet known whether the initial gain in body mass during creatine loading is maintained following prolonged supplementation and, if so, whether this reflects a gain in total fat-free mass (12). Up to date, most short- (1-3,11,13,20,28) and long-term (9,12,21,27,29) studies about creatine supplementation have Address for correspondence: Ita Pfeferman Heilberg, M.D., PhD, Univer- sidade Federal de Silo Paulo, Nephrology Division, Rua: Botucatu, 740, Vila Clementino - Silo Paulo - SP, Brazil. 04023-900; E-mail: ipheilberg@nefro.epm.br. Submitted for publication January 2005. Accepted for publication April 2005. 0195-9131/05/3709-1525/0 MEDICINE & SCIENCE IN SPORTS & EXERCISE, Copyright 0 2005 by the American College of Sports Medicine DOI: 10.1249/01.mss.0000177555.94271.44 focused on ergogenic capacity but the effects of long-term use of oral creatine on renal function have not been well established. Whereas some studies did not report any alter- ation in renal function after creatine supplementation (12,21,23,24), others have observed that it can speed up renal disease progression (4,19). The lack of biochemical evidence about an eventual im- pairment of kidney function in controlled human studies relies, at least in part, on the difficulties concerning mea- surement of glomerular filtration rate (GFR). Because cre- atine is converted to creatinine, creatine supplementation may interfere with creatinine determination and conse- quently superestimate the value of creatinine clearance, a classic estimate of GFR. In order to prevent the bias of analytical interference by tubular secreted creatinine, gold- standard methods such as inulin clearance should be used instead. However, human studies are difficult to perform because inulin has to be injected and the procedure is time consuming. The purpose of the present study was to evaluate the effects of long-term creatine supplementation with or with- out physical exercise on total body composition (fat and lean mass) and renal function in an experimental model in rats. MATERIALS AND METHODS Animals. In all experiments, all ACSM guidelines for animal care were followed, and all protocols were autho- rized by the committee for ethics in animal research of the Institute of Biomedical Sciences (protocol no. 959/01), in 1525