Creatine to Enhance Sports Performance
October 2000; Volume 3; 112-115
By Dónal P. O’Mathúna, PhD
The olympic games have come and gone. elite athletes from around the world lined up in Australia and impressed us with their talents and perseverance. Gold, silver, and bronze were awarded—the fruit of years of training, coaching, and, in some cases, drugs.
The nagging question of how "clean" an athlete’s performance should be is raised at nearly every major sports event. For years we have pretended that the rare occasion of a snared athlete proved that performance-enhancing drugs rarely were used. In reality, some athletes at all levels are taking these substances. Each raises questions of medical safety.
Since creatine was last reviewed in these pages,1 official bodies have weighed in. The International Olympic Committee and the National Collegiate Athletic Association (NCAA) do not ban creatine, but in June 2000 the NCAA declared that college and university funds could no longer supply athletes with creatine.2 The American College of Sports Medicine recommends against creatine supplementation for those under 18 years because data are completely lacking for this population.3 Many high school and college football programs openly or quietly support its use. And its use is greater than ever—2.5 million kg of creatine was used in dietary supplements in the United States in 1999.3
Background
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 than sedentary foxes raised in captivity.4 Soon afterward, creatine levels were seen to correlate with muscle mass and urinary levels of creatinine, now known to be a byproduct of creatine metabolism. In spite of this early interest, it wasn’t until the 1990s that creatine burst onto the athletic scene as a potent ergogenic aid (i.e., a performance-enhancing substance).
Pharmacology
Creatine is made from three amino acids common to protein. On average, people require about 2 g/d creatine, which they obtain in roughly equal amounts from exogenous and endogenous sources.5 Vegetarians rely primarily on endogenous production by their livers and kidneys. Humans store 95% of their creatine in skeletal muscle, with more found in fast-twitch muscle fibers than in 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 becomes adenosine diphosphate. Muscle ATP stores provide fuel for only a few seconds of exercise, after which CP replenishes ATP. (See Figure 1.) Muscle CP stores contain fuel for four to six additional seconds of intense exercise; the replenishment rate of CP depends on free creatine concentrations.6
Creatine is thus essential for short, intense, anaerobic exercise.4 Thirty seconds of rest will half-replenish CP levels, though complete recovery may take up to 3-4 minutes.7
Mechanism of Action
Supplemental creatine reasonably could be expected to enhance performance via two mechanisms. Increased CP stores would make more energy immediately available to muscles. And, increased free creatine would allow depleted CP stores to recover faster and thus shorten recovery periods during repeated bouts of intense exercise.
Creatine supplementation increases plasma creatine concentrations (up to eight times normal after 5 g).8 Supplementation (5 g, 4-6 times daily, for at least three days) led to a significant (17%) increase in muscle creatine content, with 20-40% of the increase being in CP levels.8 However, more than half of the creatine was excreted unchanged in the urine, with more excreted as supplementation continued. Increased plasma and muscle levels varied considerably between subjects. The largest changes occurred with two vegetarians whose creatine levels were the lowest to start; the smallest changes were seen in those whose creatine levels were highest to start.8 Upon ceasing supplementation, muscle levels returned to normal within four weeks.3
Clinical Studies
Many clinical studies have been conducted with creatine, though none with more than 40 subjects. Thirty-four controlled studies reviewed in 1998 used, on average, 12 subjects.9 A 1999 review found 17 studies that showed some performance improvements, although six had both positive and negative findings.4 Most of these studies used 20 g creatine for five days and measured outcomes on various exercise machines. Another 11 studies using similar supplementation produced no performance improvements with mostly repeated sprints (running or swimming).
This year, four additional randomized, double-blind trials have been published and one meta-analysis presented.
In one study, 14 Spanish competitive male cyclists took either placebo or creatine (5 g qid for five days) and rode bicycle ergometers alternating every three minutes between 30% and 90% maximum output.10 The time to exhaustion increased from 29.9 to 36.5 minutes in the creatine group (P < 0.05) and was unchanged with placebo.
Another Spanish study randomly assigned 17 highly trained male soccer players to creatine (5 g qid for six days) or placebo.11 The sum of 6 x 5 meter and 6 x 15 meter sprint times improved significantly for the creatine group, as did the average 5-meter time (P < 0.05). However, the average 15-meter time and two jumping tests showed no significant changes.
A South African study randomly assigned 15 competitive weight lifters to placebo (n = 5) or creatine (3 g tid for six days).12 Three bouts of isokinetic knee extension exercises were conducted, with power and work output measured six ways. Of these 18 measurements, six improved significantly with creatine (P < 0.03) and five with placebo (P < 0.05). Product promotional materials claimed five days of creatine supplementation would give trained athletes a 5% performance improvement. The average dead lift increased 7.81 kg after creatine supplementation (2.6% improvement, P < 0.02). Those taking placebo lifted 7.00 kg more (2.3% improvement), not a statistically significant change. However, the researchers noted that inequalities between the two groups may have led to the differences and urged caution in generalizing their results.
In a U.S. study, researchers randomly assigned 23 male weight lifters to receive placebo (n = 13) or creatine (5 g qid for five days).13 Arm flexor muscle strength increased significantly compared to pretest values for both the creatine (29.9%) and placebo (16.5%) groups (P < 0.01). The percent increase for creatine was significantly greater than for placebo (P < 0.01). Upper arm circumference and muscle area also increased significantly more in the creatine group (P < 0.01).
An unpublished meta-analysis of 32 studies presented at the American College of Sports Medicine 2000 meeting showed no overall effect of creatine supplementation on anaerobic performance.2
Adverse Effects
Creatine causes weight gain of 1-3 kg because of water retention.3 Numerous anecdotal reports claim creatine supplementation causes gastrointestinal problems, muscle cramping, and renal problems. Controlled studies generally do not support these concerns. Creatine caused gastrointestinal problems during studies only when ingested immediately before or during exercise.14 Two case studies reported renal problems that resolved upon ceasing creatine supplementation.15,16 One patient had preexisting renal problems. A small study of healthy athletes taking 10 g/d creatine for up to five years revealed no impaired renal function.14 Those with preexisting renal dysfunction or at high risk for renal disease should be monitored medically.3
Drug Interactions
No drug interactions are known, although one athlete had an ischemic stroke after daily consumption of 6 g creatine, 400-600 mg caffeine, 40-60 mg ephedra, and several other supplements.2 Theoretically, creatine could interact with other drugs with renal toxicity.
Formulation
Readily available from meat and fish (containing roughly 4-5 g/kg), creatine 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 these provide added benefits. Usually, athletes "load" on 20 g/d creatine 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.17 (See Table 1.)
| Table 1-Creatine price and formulation comparison | |||
| Manufacturer/Product | Formulation per Serving | Manufacturer's Recommended Dose | Price/Quantity |
| Muscle Link Effervescent Creatine Elite |
5 g creatine monohydrate (99.5% pure) and 20 g dextrose |
Mix contents of one packet in 16 oz water or sports drink |
$41.99/20 packets (27 g each) |
| Met-Rx Anabolic Drive Series Creatine Accumulation Complex, Grape Punch Powder |
12.4 g micronized creatine, 400 mg alpha-lipoic acid, 10 g glutamine peptide |
Add three scoops to 16 oz cold water and stir until dissolved. Use one serving daily. |
$34.99/44.4 oz |
| Challenge Creatine Monohydrate | 500 mg creatine monohydrate; meets USP weight and disintegration requirements |
Maintenance: 10 tabs/d Loading: 40 tabs/d (10 tabs at four hour intervals). Ensure adequate liquid intake |
$34.99/500 tabs |
| Champion Nutrition Creatine Xtreme Island Punch |
6 g pure creatine monohydrate, 1,000 mg taurine, 500 mg L-Glutamine, 500 mg L-Glutamic acid, 200 mg hydroxycitrate, 15 mg vanadyl nicotinate, 120 µg chromium |
Maintenance: mix one scoop with 8 oz water, bid Loading: mix one scoop with 8 oz water, 5 times/d |
$29.95/920 g |
| Optimum Nutrition Creatine Liquid Energy, Tropical Punch |
6 g 99.9% pure pharmaceutical grade creatine monohydrate, 500 mg methylsulfonylmethane (MSM) |
Maintenance: 2 tablespoons/d for 8-10 weeks Loading: 2 tablespoons 4-5 times/d for 3-5 days |
$14.99/16 oz |
| Source: online mail-order companies | |||
Conclusion
In spite of the variable research results, some patterns are recognizable.9 Oral creatine supplementation does not improve single-bout anaerobic exercise, submaximal exercise, or aerobic exercise. Improvements occur primarily with repeated bouts of maximal exertion lasting 6-30 seconds with a few minutes recovery (CP-dependent exercise), such as many football plays, running bases, or playing soccer. This sort of protocol would allow athletes to train more vigorously and could indirectly improve performances. 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 unresponsive.
Recommendation
The performance of athletes involved in high-intensity, repeated exercise of very short duration may benefit from creatine supplementation of 2 g/d. Recreational and endurance athletes will not benefit from creatine. Few adverse effects have been found, but long-term effects have received little study. Clinicians should ask athletic patients if they take such supplements. Most probably will not be training at the intensity needed to see any benefits, and should be cautioned about the potential risks. Anyone susceptible to renal damage should not use creatine. Parents of promising athletes must choose between the unclear potential benefits and the unknown risks of taking creatine supplements, especially for extended periods. The psychological impact of the pressure to win must not override sound judgment.
Dr. O’Mathúna is Professor of Bioethics and Chemistry at Mount Carmel College of Nursing in Columbus, OH.
References
1. Barrette EP. Creatine supplementation for enhancement of athletic performance. Altern Med Alert 1998;1:73-77.
2. Creatine. Natural Medicines Comprehensive Database. Stockton, CA: Therapeutic Research Center. Available at: www.naturaldatabase.com. Accessed July 26, 2000.
3. Terjung RL, et al. The physiological and health effects of oral creatine supplementation. Med Sci Sports Exerc 2000;32:706-717.
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. Harris RC, et al. Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clin Sci 1992;83:367-374.
9. Juhn MS, Tarnopolsky M. Oral creatine supplementation and athletic performance: A critical review. Clin J Sport Med 1998;8:286-297.
10. Rico-Sanz J, Mendez Marco MT. Creatine enhances oxygen uptake and performance during alternating intensity exercise. Med Sci Sports Exerc 2000;32:379-385.
11. Mujika I, et al. Creatine supplementation and sprint performance in soccer players. Med Sci Sports Exerc 2000;32:518-525.
12. Rossouw F, et al. The effect of creatine monohydrate loading on maximal intermittent exercise and sport-specific strength in well trained power-lifters. Nutr Res 2000;20:505-514.
13. Becque MD, et al. Effects of oral creatine supplementation on muscular strength and body composition. Med Sci Sports Exerc 2000;32:654-658.
14. 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.
15. Koshy KM, et al. Interstitial nephritis in a patient taking creatine. N Engl J Med 1999;340:814-815.
16. Pritchard NR, Kalra PA. Renal dysfunction accompanying oral creatine supplements. Lancet 1998;351:1252-1253.
17. Hultman E, et al. Muscle creatine loading in men. J Appl Physiol 1996;81:232-237.
October 2000; Volume 3; 112-115
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