By Dónal P. O’Mathúna
Athletes, competitive and recreational, are increasingly using dietary supplements and nutritional aids. Creatine is one of the most popular supplements among competitive athletes. A 2004 survey involving more than 200 varsity athletes at a Division 1 university found that 37.2% reported using creatine.1 Users were almost exclusively male and used creatine to increase muscle mass and strength. Other surveys found between 28% and 41% of all student-athletes at National Collegiate Athletic Association (NCAA) institutions use creatine, primarily in power sports (boxing, track and field, and those involving weightlifting).2 Creatine is not included in the list of banned substances adopted just prior to the 2004 Olympics, which, for the first time, had been adopted by all countries and for all sports.3 However, NCAA institutions are not permitted to provide athletes creatine as a nutritional supplement.2
Creatine use among recreational athletes is undocumented, but it is widely advertised and promoted as an aid to building muscle mass and strength. Physicians should be aware of this use and the claims made about creatine. Almost half the athletes in the 2004 Division 1 survey claimed they used creatine "for their health," yet physicians and pharmacists were 10th and 15th, respectively, among those used as sources of information on supplements.1 The most popular sources were family members, fellow athletes, and strength coaches.
Creatine’s role in exercise was discovered in 1847 when wild foxes killed after foxhunts were found to have more than 10 times the amount of creatine in their meat compared to foxes raised in captivity.4 Soon afterwards, creatine levels were correlated with muscle mass and urinary levels of creatinine, now known to be a byproduct of creatine metabolism. In spite of this early interest, creatine didn’t burst onto the athletic scene as a potent ergogenic aid (i.e., a performance-enhancing substance) until the 1990s.
Pharmacology
Creatine is made from three amino acids common to protein. On average, people require about 2 g of creatine daily, obtained equally from exogenous and endogenous sources.5 Humans store 95% of their creatine in skeletal muscle, with more found in fast-twitch muscle fibers than slow-twitch ones.4
Creatine is vital to the supply of energy for short-duration, high-intensity exercise, such as sprinting, jumping, power-lifting, and tackling. About 60% of the creatine in skeletal muscle exists as creatine phosphate (CP). Adenosine triphosphate (ATP) supplies energy for muscle contraction as it is converted into adenosine diphosphate (ADP). Muscle ATP stores provide fuel for only a few seconds of exercise, after which CP replenishes ATP (see Figure). Muscle CP stores contain fuel for 4-6 additional seconds of intense exercise, and its rate of replenishment depends on free creatine concentrations.6 Creatine is thus essential for short, intense, anaerobic exercise. Thirty seconds of rest will half-replenish CP levels, though complete recovery may take up to 3-4 minutes.7
Mechanism of Action
The mechanism of action by which creatine supplementation could increase muscle strength and athletic performance is not known with certainty. However, a number of physiological mechanisms have been proposed and are being investigated. Studies have provided evidence that up to 40% of the ergogenic effect could be due to a direct effect of making more creatine and CP available for muscle energy production.8
As CP stores are depleted with exercise, increased free plasma creatine would allow faster replenishment of CP stores and thus shorten recovery periods during repeated bouts of intense exercise. Athletes consuming creatine have been found to tolerate higher exercise volumes, which may thereby produce greater strength.8 Creatine also has been proposed to contribute to muscle fiber hypertrophy, to activate gene expression that leads to muscle growth, and to increase total body water.8 The latter may influence glycogen levels and increase the rate of muscle protein synthesis and/or decrease the rate of muscle protein breakdown.
These different mechanisms could contribute to increased muscle mass and strength. Variation in their influence could account for one of the ongoing controversies regarding creatine supplementation, namely, the great variability in individual responses to supplementation.
Clinical Studies
Creatine is one of the few ergogenic aids that has been extensively researched. When reviewed in this newsletter in 2000, several dozen small studies showed some ergogenic benefit but with considerable variability.9 Several hundred studies of creatine have now been published, with one review estimating that 70% of these found at least some ergogenic benefit.8
The first meta-analysis of studies examining the impact of creatine on strength performance was published in 2002.10 Of 66 studies identified, 16 met the inclusion criteria. Only studies measuring strength or power (and not endurance) were included, and all crossover studies were excluded because of controversy over the appropriate washout period. The analysis showed that creatine supplementation improves maximal resistance training performance in previously trained young men. Benefits were found only when supplementation was accompanied by resistance training. Improvements were not found with more complex exercise involving strength, speed, and coordination of several muscles, nor were they found in untrained men, women, or older adults. However, the analysis also reported poor overall study quality, with an average score of 3.5 out of 10 and the best score being 5.5.
A 2003 meta-analysis examined 100 studies.11 The inclusion criteria were broader than those above, including all randomized, placebo-controlled, blinded studies that measured any body composition or physical performance outcome. Although the results of individual studies were considerably variable, certain overall patterns emerged. The mean overall improvement after creatine supplementation (5.7% ± 0.5%) was significantly greater than after placebo (2.4% ± 0.4%). The authors concluded that creatine is effective in increasing total and lean body mass, and improving performance in high-intensity, short-duration, repetitive exercise. For example, of the 62 studies examining exercise duration of less than 30 seconds, 45 reported an ergogenic effect from creatine and 17 reported no benefit, for an overall effect size of 0.24 ± 0.02. Eighteen studies examining exercise of 150 seconds or longer found an equal number with and without ergogenic benefits.
A number of other patterns emerged from this meta-analysis. Benefits were greater when supplementation continued at a lower dose after the initial loading dose. Few studies included women, and most of these found no ergogenic benefit. Creatine supplementation led to more pronounced benefit with upper-body exercise than lower-body or overall body exercise. Most studies involved controlled laboratory settings, but the few conducted in the field found creatine to lead to minimal improvement in running, swimming, or jumping performance. This may be due to the weight gain consistently found with creatine supplementation.8
Adverse Effects
Creatine frequently leads to weight gain of 1-3 kg, which is believed to be due to intramuscular water retention resulting from an osmotic effect.11 Numerous anecdotal reports claim creatine supplementation causes gastrointestinal problems, muscle cramping, and renal problems. Controlled studies generally do not support these concerns. A few case studies reported renal problems after creatine supplementation, especially with extended high-dose usage.12 However, a small study of healthy athletes taking 10 g creatine daily for as long as five years revealed no impaired renal function.12 Supplement use appears generally safe, although those at high risk for renal disease should be monitored medically.13
The NCAA and International Olympic Committee (IOC) do not ban creatine but warn about the risk of contamination with banned substances. An IOC study of more than 600 non-hormonal nutritional supplements purchased in 13 countries found 14.8% to be contaminated with hormones that were not listed on the labels.14 Tests showed that consumption led to urine levels that would have resulted in positive doping results.
No drug interactions are known, although creatine could interact with other drugs associated with renal toxicity.
Formulation
Creatine is readily available from meat and fish (containing roughly 4-5 g/kg) and therefore is classified as a dietary supplement, not a drug. It is most commonly available as the monohydrate in powder, candy, gum, and liquid. Numerous products combine it with vitamins, nutrients, and supplements, with no evidence of added benefits. Usually, athletes "load" on 20 g creatine per day for 4-6 days (usually 5 g qid), followed by one 2 g daily dose. The same creatine "loading" levels are achieved after 30 days of 3 g/d taken as a single dose.15
Conclusion
Oral creatine supplementation has been studied extensively over the past decade. Ergogenic improvements consistently occur with repeated bouts of maximal exertion lasting less than 30 seconds with a few minutes recovery—such as high-intensity weight-lifting, football plays, and short-burst training programs. The metabolic rationale for such benefits is well-established. Those most likely to benefit from supplementation are young, well-trained males. Very little evidence supports improvements with single-bout anaerobic exercise, submaximal exercise, or aerobic exercise. Most studies have been conducted in controlled environments and may not be replicable in competition. Additionally, people vary widely in their response to supplementation, with some being wholly unresponsive.
Recommendation
High-performance athletes involved in high-intensity, repeated exercise of very short duration may benefit from creatine supplementation with 2 g/d. Recreational and endurance athletes probably will not benefit from creatine. Adverse effects are rare, although few long-term studies have been conducted. Clinicians should ask their athletic patients if they take such supplements. Most will probably not be training at the intensity needed to see any benefit. Those who are highly competitive should be cautioned about the risks of contaminated products. Clinicians should remain informed of the latest developments in creatine research, so they can advise their patients, especially those who may be susceptible to renal damage.
Dr. O’Mathúna is a lecturer at the School of Nursing, Dublin City University, Ireland.
References
1. Froiland K, et al. Nutritional supplement use among college athletes and their sources of information. Int J Sport Nutr Exerc Metab 2004;14:104-120.
2. Meiggs R. Committee continues to monitor creatine use in sports. April 12, 2004. Available at: www1.ncaa.org/membership/ed_outreach/health-safety/Creatine04.pdf. Accessed on July 31, 2004.
3. World Anti-Doping Agency. The 2004 Prohibited List International Standard. March 17, 2004. Available at: www.wada-ama.org/docs/web/standards_harmonization/code/list_standard_2004.pdf. Accessed on July 31, 2004.
4. Demant TW, Rhodes EC. Effects of creatine supplementation on exercise performance. Sports Med 1999;28:49-60.
5. Benzi G. Is there a rationale for the use of creatine either as nutritional supplementation or drug administration in humans participating in a sport? Pharmacol Res 2000;41: 255-264.
6. Feldman EB. Creatine: A dietary supplement and ergogenic aid. Nutr Rev 1999;57:45-50.
7. Hahn AG. Physiology of training. In Bloomfield J, et al, eds. Textbook of Science and Medicine in Sport. Champaign, IL: Human Kinetics Books; 1992:66-86.
8. Volek JS, Rawson ES. Scientific basis and practical aspects of creatine supplementation for athletes. Nutr 2004;20:609-614.
9. O’Mathúna D. Creatine to enhance sports performance. Altern Med Alert 2000;3:112-115.
10. Dempsey RL, et al. Does oral creatine supplementation improve strength? A meta-analysis. J Fam Pract 2002;51: 945-951.
11. Branch JD. Effect of creatine supplementation on body composition and performance: A meta-analysis. Int J Sport Nutr Exerc Metab 2003;13:198-226.
12. 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.
13. Yoshizumi WM, Tsourounis C. Effects of creatine supplementation on renal function. J Herb Pharmacother 2003;4:1-7.
14. Schänzer W. Analysis of non-hormonal nutritional supplements for anabolic-androgenic steroids—an international study. Available at: http://multimedia.olympic.org/pdf/en_report_324.pdf. Accessed on July 31, 2004.
15. Hultman E, et al. Muscle creatine loading in men. J Appl Physiol 1996;81:232-237.
O'Mathuna DP. Creatine to improve muscle strength. Altern Med Alert 2004;7(11):128-131.
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