Background/Aims: Caffeine and creatine are 2 of the most widely available and used compounds in sport. Although the use of either is not considered a doping infraction, the evidence does suggest ergogenic potential in certain sports. The purpose of this paper is to review the pharmacology and potential mechanism(s) of action of caffeine and creatine as they pertain to possible use as an ergogenic aid in sport. Methods: Previous review articles on caffeine and creatine use in sport were screened for relevant information and references, and studies for review and recent articles (2007 onwards) were obtained and reviewed using a PUBMED search with the terms ‘caffeine AND exercise’, ‘creatine and creatine monohydrate AND exercise’, and appropriate linked articles were evaluated. Results: Caffeine taken before (3–6 mg/kg) or during (1–2 mg/kg) endurance exercise enhances performance, through central nervous system and direct muscle effects. Creatine monohydrate supplementation at higher (approx. 20 g/day × 3–5 days) or lower (approx. 5 g/day × 30 days) doses increases skeletal muscle total and phosphocreatine by 10–20%. Creatine supplementation appears to minimally but significantly enhance high-intensity sport performance and the mass and possibly strength gains made during resistance exercise training over the first few months. Conclusions: Although caffeine and creatine appear to be ergogenic aids, they do so in a sport-specific context and there is no rationale for their simultaneous use in sport. Higher doses of caffeine can be toxic and appear to be ergolytic. There is no rationale for creatine doses in excess of the recommendations, and some athletes can get stomach upset, especially at higher creatine doses.

1.
Graham TE: Caffeine, coffee and ephedrine: impact on exercise performance and metabolism. Can J Appl Physiol 2001;26 (suppl):S103–S119.
2.
Graham TE, et al: Does caffeine alter muscle carbohydrate and fat metabolism during exercise? Appl Physiol Nutr Metab 2008;33:1311–1318.
3.
Tarnopolsky MA: Caffeine and endurance performance. Sports Med 1994;18:109–125.
4.
Kreider RB: Effects of creatine supplementation on performance and training adaptations. Mol Cell Biochem 2003;244:89–94.
5.
Terjung RL, et al: American College of Sports Medicine roundtable. The physiological and health effects of oral creatine supplementation. Med Sci Sports Exerc 2000;32:706–717.
6.
Tarnopolsky MA: Clinical use of creatine in neuromuscular and neurometabolic disorders. Subcell Biochem 2007;46:183–204.
7.
Greenhaff PL: Creatine and its application as an ergogenic aid. Int J Sport Nutr 1995;5(suppl):S100–S110.
8.
Kot M, Daniel WA: Caffeine as a marker substrate for testing cytochrome P450 activity in human and rat. Pharmacol Rep 2008;60:789–797.
9.
Chen X, et al: The G-113A polymorphism in CYP1A2 affects the caffeine metabolic ratio in a Chinese population. Clin Pharmacol Ther 2005;78:249–259.
10.
Robertson D, et al: Tolerance to the humoral and hemodynamic effects of caffeine in man. J Clin Invest 1981;67:1111–1117.
11.
Fisher SM, et al: Influence of caffeine on exercise performance in habitual caffeine users. Int J Sports Med 1986;7:276–280.
12.
Van Soeren MH, et al: Caffeine metabolism and epinephrine responses during exercise in users and nonusers. J Appl Physiol 1993;75:805–812.
13.
Ivy JL, et al: Influence of caffeine and carbohydrate feedings on endurance performance. Med Sci Sports 1979;11:6–11.
14.
Costill DL, Dalsky GP, Fink WJ: Effects of caffeine ingestion on metabolism and exercise performance. Med Sci Sports 1978;10:155–158.
15.
Tarnopolsky MA: Effect of caffeine on the neuromuscular system – Potential as an ergogenic aid. Appl Physiol Nutr Metab 2008;33:1284–1289.
16.
Weber A, Herz R: The relationship between caffeine contracture of intact muscle and the effect of caffeine on reticulum. J Gen Physiol 1968;52:750–759.
17.
Tarnopolsky M, Cupido C: Caffeine potentiates low frequency skeletal muscle force in habitual and nonhabitual caffeine consumers. J Appl Physiol 2000;89:1719–1724.
18.
Lopes JM, et al: Effect of caffeine on skeletal muscle function before and after fatigue. J Appl Physiol 1983;54:1303–1305.
19.
Westerblad H, Allen DG: Mechanisms underlying changes of tetanic [Ca2+]i and force in skeletal muscle. Acta Physiol Scand 1996;156:407–416.
20.
Lindinger MI, Graham TE, Spriet LL: Caffeine attenuates the exercise-induced increase in plasma [K+] in humans. J Appl Physiol 1993;74:1149–1155.
21.
Cox GR, et al: Effect of different protocols of caffeine intake on metabolism and endurance performance. J Appl Physiol 2002;93:990–999.
22.
Jackman M, et al: Metabolic catecholamine, and endurance responses to caffeine during intense exercise. J Appl Physiol 1996;81:1658–1663.
23.
van Dam RM: Coffee consumption and risk of type 2 diabetes, cardiovascular diseases, and cancer. Appl Physiol Nutr Metab 2008;33:1269–1283.
24.
Robinson LE, et al: Caffeine ingestion before an oral glucose tolerance test impairs blood glucose management in men with type 2 diabetes. J Nutr 2004;134:2528–2533.
25.
Harris RC, et al: The concentration of creatine in meat, offal and commercial dog food. Res Vet Sci 1997;62:58–62.
26.
Wallimann T, et al: Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the ‘phosphocreatine circuit’ for cellular energy homeostasis. Biochem J 1992;281:21–40.
27.
Safdar A, et al: Global and targeted gene expression and protein content in skeletal muscle of young men following short-term creatine monohydrate supplementation. Physiol Genomics 2008;32:219–228.
28.
Tarnopolsky MA, Beal MF: Potential for creatine and other therapies targeting cellular energy dysfunction in neurological disorders. Ann Neurol 2001;49:561–574.
29.
Harris RC, Soderlund K, Hultman E: Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clin Sci (Lond) 1992;83:367–374.
30.
Hultman E, et al: Muscle creatine loading in men. J Appl Physiol 1996;81:232–237.
31.
Greenhaff PL, et al: Influence of oral creatine supplementation of muscle torque during repeated bouts of maximal voluntary exercise in man. Clin Sci (Lond) 1993;84:565–571.
32.
Birch R, Noble D, Greenhaff PL: The influence of dietary creatine supplementation on performance during repeated bouts of maximal isokinetic cycling in man. Eur J Appl Physiol Occup Physiol 1994;69:268–276.
33.
Casey A, et al: Creatine ingestion favorably affects performance and muscle metabolism during maximal exercise in humans. Am J Physiol 1996;271:E31–E37.
34.
Anomasiri W, Sanguanrungsirikul S, Saichandee P: Low dose creatine supplementation enhances sprint phase of 400 meters swimming performance. J Med Assoc Thai 2004;87(suppl 2):S228–S232.
35.
Vandebuerie F, et al: Effect of creatine loading on endurance capacity and sprint power in cyclists. Int J Sports Med 1998;19:490–495.
36.
Mihic S, et al: Acute creatine loading increases fat-free mass, but does not affect blood pressure, plasma creatinine, or CK activity in men and women. Med Sci Sports Exerc 2000;32:291–296.
37.
Becque MD, Lochmann JD, Melrose DR: Effects of oral creatine supplementation on muscular strength and body composition. Med Sci Sports Exerc 2000;32:654–658.
38.
Vandenberghe K, et al: Long-term creatine intake is beneficial to muscle performance during resistance training. J Appl Physiol 1997;83:2055–2063.
39.
Jowko E, et al: Creatine and beta-hydroxy-beta-methylbutyrate (HMB) additively increase lean body mass and muscle strength during a weight-training program. Nutrition 2001;17:558–566.
40.
Kreider RB, et al: Effects of creatine supplementation on body composition, strength, and sprint performance. Med Sci Sports Exerc 1998;30:73–82.
41.
Brose A, Parise G, Tarnopolsky MA: Creatine supplementation enhances isometric strength and body composition improvements following strength exercise training in older adults. J Gerontol A Biol Sci Med Sci 2003;58:11–19.
42.
Chrusch MJ, et al: Creatine supplementation combined with resistance training in older men. Med Sci Sports Exerc 2001;33:2111–2117.
43.
Tarnopolsky MA, Safdar A: The potential benefits of creatine and conjugated linoleic acid as adjuncts to resistance training in older adults. Appl Physiol Nutr Metab 2008;33:213–227.
44.
Balsom PD, et al: Creatine supplementation per se does not enhance endurance exercise performance. Acta Physiol Scand 1993;149:521–523.
45.
Koshy KM, Griswold E, Schneeberger EE: Interstitial nephritis in a patient taking creatine. N Engl J Med 1999;340:814–815.
46.
Pritchard NR, Kalra PA: Renal dysfunction accompanying oral creatine supplements. Lancet 1998;351:1252–1253.
47.
Poortmans JR, et al: Effect of short-term creatine supplementation on renal responses in men. Eur J Appl Physiol Occup Physiol 1997;76:566–567.
48.
Poortmans JR, Francaux M: Long-term oral creatine supplementation does not impair renal function in healthy athletes. Med Sci Sports Exerc 1999;31:1108–1110.
49.
Tarnopolsky M, et al: Creatine monohydrate and conjugated linoleic acid improve strength and body composition following resistance exercise in older adults. PLoS One 2007;2:e991.
50.
Kreider RB, et al: Long-term creatine supplementation does not significantly affect clinical markers of health in athletes. Mol Cell Biochem 2003;244:95–104.
51.
Tarnopolsky MA, et al: Creatine monohydrate enhances strength and body composition in Duchenne muscular dystrophy. Neurology 2004;62:1771–1777.
52.
Groeneveld GJ, et al: A randomized sequential trial of creatine in amyotrophic lateral sclerosis. Ann Neurol 2003;53:437–445.
53.
Wyss M, Kaddurah-Daouk R: Creatine and creatinine metabolism. Physiol Rev 2000;80:1107–1213.
54.
Tarnopolsky MA, et al: Histological assessment of intermediate- and long-term creatine monohydrate supplementation in mice and rats. Am J Physiol Regul Integr Comp Physiol 2003;285:R762–R769.
55.
Volek JS, et al: Physiological responses to short-term exercise in the heat after creatine loading. Med Sci Sports Exerc 2001;33:1101–1108.
56.
Yang L, et al: Combination therapy with coenzyme Q10 and creatine produces additive neuroprotective effects in models of Parkinson’s and Huntington’s diseases. J Neurochem 2009;109:1427–1439.
57.
Zhu S, et al: Prophylactic creatine administration mediates neuroprotection in cerebral ischemia in mice. J Neurosci 2004;24:5909–5912.
58.
Louis M, et al: Beneficial effects of creatine supplementation in dystrophic patients. Muscle Nerve 2003;27:604–610.
59.
Kley R, Vorgerd M, Tarnopolsky M: Creatine for treating muscle disorders. Cochrane Database Syst Rev 2007:CD004760.
60.
Vandenberghe K, et al: Caffeine counteracts the ergogenic action of muscle creatine loading. J Appl Physiol 1996;80:452–457.
61.
Desbrow B, et al: An examination of consumer exposure to caffeine from retail coffee outlets. Food Chem Toxicol 2007;45:1588–1592.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.