Creatine ingestion favorably affects performance and muscle metabolism during maximal exercise in humans A. CASEY, D. CONSTANTIN-TEODOSIU, S. HOWELL, E. HULTMAN, AND P. L. GREENHAFF Department of Physiology and Pharmacology, University of Nottingham Medical School, Queen’s Medical Center, Nottingham NG7 2UH, United Kingdom; and Department of Clinical Chemistry, Karolinska Institute, Huddinge University Hospital, S-141 86 Huddinge, Sweden Casey, A., D. Constantin-Teodosiu, S. Howell, E. Hult- man, and P. L. Greenhaff. Creatine ingestion favorably affects performance and muscle metabolism during maximal exercise in humans. Am. J. Physiol. 271 (Endocrinol. Metab. 34): E31-E37, 1996.-Nine male subjects performed two bouts of 30-s maximal isokinetic cycling before and after ingestion of 20 g creatine (Cr) monohydrate/day for 5 days. Cr ingestion produced a 23.1 ? 4.7 mmol/kg dry matter increase in the muscle total creatine (TCr) concentration. Total work production during bouts 1 and 2 increased by -4%, and the cumulative increases in both peak and total work production over the two exercise bouts were positively correlated with the increase in muscle TCr. Cumulative loss of ATP was 30.7 2 12.2% less after Cr ingestion, despite the increase in work production. Resting phosphocreatine (PC,) increased in type I and II fibers. Changes in PCr before exercise bouts 1 and 2 in type II fibers were positively correlated with changes in PCr degradation during exercise in this fiber type and changes in total work production. The results suggest that improvements in performance were mediated via improved ATP resynthesis as a consequence of increased PCr availabil- ity in type II fibers. phosphocreatine; adenosine 5’-triphosphate; muscle fiber types FATIGUE SUSTAINED DURING short-term maximal-inten- sity exercise in humans has been associated with the inability of skeletal muscle to maintain a high rate of anaerobic ATP production from phosphocreatine (PC,) hydrolysis (6, 18, 21). Furthermore, evidence is also available to suggest that fatigue under these conditions may be attributable to an impairment of ATP produc- tion predominantly in type II muscle fibers, in which the PCr concentration is rapidly depleted (7a, 25). Harris et al. (16) were the first to demonstrate that ingestion of 5 g creatine (Cr) monohydrate on four to six occasions each day for several consecutive days could increase the total creatine (TCr; XPCr and Cr) concen- tration of human skeletal muscle by an average of 25 mmol/kg dry matter, some 30% of which occurred in phosphorylated form as PCr. The authors went on to suggest that these changes might have a beneficial effect on exercise performance in humans, and indeed recent placebo controlled studies, using a variety of experimental models, have confirmed that dietary Cr supplementation can improve exercise performance during repeated bouts of maximal-intensity exercise (1, 5,8,12, 17). To date, there has been no direct investigation of the effects of Cr ingestion on muscle metabolism during maximal-intensity ‘dynamic exercise. However, several of the performance studies cited above found a reduc- tion in plasma ammonia (5, 12) and hypoxanthine (1) accumulation during exercise after Cr ingestion, de- spite increases in muscle torque/work production. As a consequence of these findings, the ergogenic effect of Cr ingestion was attributed to possible improvements in the ability of muscle to sustain ATP rephosphorylation from ADP during exercise, which may have been achieved as a result of an increase in preexercise PCr availability, an improvement in muscle buffering capac- ity, and/or an acceleration of PCr resynthesis during exercise and recovery. In support of this latter hypoth- esis, acceleration of PCr resynthesis during recovery from intense electrically evoked isometric muscle con- traction has been shown to occur after Cr supplementa- tion (11). Whether a similar relationship exists between Cr availability and changes in metabolism during maximal dynamic exercise of short duration has yet to be ascertained. The studies of Harris et al. (16) and Greenhaff et al. (11) also drew attention to the large interindividual variation in the change in muscle TCr concentration, which appeared to be at least partly related to the initial TCr concentration of the muscle. However, per- haps more importantly, Greenhaff et al. (11) showed that a measurable effect of Cr ingestion on PCr resyn- thesis during recovery from maximal-intensity exercise was only observed in individuals who demonstrated more than a 20 mmol/kg dry matter increase in muscle TCr concentration after Cr ingestion. These results suggest that a favorable effect of Cr ingestion on metabolism and performance during exercise and recov- ery may be critically dependent on the magnitude of the increase in muscle TCr concentration during supple- mentation. The aim of the present experiment, therefore, was to perform a direct investigation of the effects of Cr supplementation on skeletal muscle energy metabo- lism and performance during repeated bouts of maxi- mal exercise in humans. It was hypothesised that 1) a relationship would exist between increases in muscle Cr availability and improvements in maximal dynamic exercise performance and 2) that, since fatigue during maximal exercise is associated with a fall in ATP resynthesis from PCr degradation in type II muscle fibers (7a, 25), an increase in type II fiber PCr availabil- ity might improve the maintenance of force production via an effect on ATP resynthesis. METHODS Subjects. Nine healthy male subjects gave their written consent to take part in the present study, which was approved by the University of Nottingham Medical School Ethical 0193-1849/96 $5.00 Copyright o 1996 the American Physiological Society E31