Creatine Supplementation for Enhancement of Athletic Performance

July 1998; Volume 1: 73-77

By E. P. Barrette, MD

The pressure for athletes to excel is great. with evidence of the severe complications of anabolic steroids, athletes have looked for alternatives to boost their anaerobic performance. Bodybuilders have reportedly accepted creatine as the most effective supplement, and many products are promoted for increasing muscle mass. Creatine has rapidly become the leader in spite of lingering renal and other concerns. Clinical studies have been mixed, and long-term safety is not known. But, because of creatine's popularity, clinicians should know its pros and cons.

History

Creatine was first identified in meat extract in the 1830s by Chevreul. Creatine supplements did appear to improve performance in rats in 1923; creatine's role in muscle contraction was elaborated by 1930.

Human studies did not appear for 60 years. In 1981, the earliest published study of creatine supplements was reported in patients with gyrate atrophy of the choroid and retina.1 Seven patients received 1.5 g for one year, which slowed progression of their disease. Some of the patients reported increased strength while receiving creatine, and one long-distance runner improved his 100 m sprint time. In 1992, Harris reported that 4-6 doses daily of 5 g of creatine for up to 10 days significantly increased total creatine content of the quadriceps muscle.2

Mechanism of Action

During brief, intense exercise, maximal efforts result in rapid depletion of creatine phosphate, which is used to replenish ATP. The onset of fatigue is partly explained by the inability of creatine phosphate to maintain the ATP/ADP ratio. During high intensity exercises, ATP regeneration is an anaerobic process. The hypothesis that increasing the creatine phosphate pool would result in improved short-term performance led to creatine supplement trials.

Two proposed mechanisms for improved muscle performance with creatine supplements include increased creatine phosphate synthesis from creatine during recovery from intense muscular contraction; and an attenuation of the loss of ATP during repeated intense muscular contractions.3,4

Biochemistry

Creatine is an amino acid, although it is not incorporated into proteins. More than 95% of total creatine is stored in skeletal muscle. Two-thirds of this total is phosphorylated as creatine phosphate. In a 70 kg man, the total creatine pool is estimated to be 120 g. Two grams are lost daily in the urine as the irreversible breakdown product, creatinine. A typical diet supplies 1-2 g of creatine a day, primarily from meat and fish. Endogenous biosynthesis from glycine, arginine, and methionine provides the rest; creatine supplementation suppresses endogenous biosynthesis.

Total creatine can be increased by approximately 20% with oral supplements, and 20% of the increase is stored as creatine phosphate. Twenty grams a day in four divided doses over 5-6 days will rapidly reach this limit.5 Two grams a day will maintain the increased level of muscle creatine. When supplements are stopped, the increased level will decrease over 30 days to the presupplement baseline.

Despite higher doses of creatine, there appears to be an upper limit of creatine storage in muscle, 150-160 mmol/kg. Presupplement muscle creatine levels vary from 115 to 150 mmol/kg (mean, 124.4 mmol/kg). Vegetarians appear to have a smaller total creatine pool (80 g vs 120 g), and it has been suggested that they may be able to increase this with supplements. However, no other factors have been identified that can predict the baseline content in muscles. This observation is important, since individuals with high baseline muscle creatine levels are not able to increase their muscle creatine. It is estimated that 20-30% of individuals will not respond to creatine supplements.

Clinical Studies

There are more than 25 studies of creatine supplements and athletic performance. Comparisons are difficult since many different protocols were used to measure performance. Since creatine supplements increase body mass, a well known fact among athletes, the degree of blinding is uncertain.

Studies of continuous aerobic activity have not shown any benefit with creatine. In a double-blind trial of 18 well-trained male athletes tested with either a 6 km run or a treadmill run to exhaustion (set for 3-6 minutes), no improvement was seen.6 In fact, the subjects randomized to creatine supplements ran slower than the subjects given placebo. The time required to complete the 6 km run was longer after creatine.

Most of the positive studies used trained athletes and have shown improvement in performance during maximal intermittent exercise. Two groups have published many of the reports. Balsom et al used 16 motivated physical education students (mean age, 26.7 years) in a double-blind protocol.7 Before and after six days of 20 g of creatine or placebo, the subjects exercised for 10 six-second bouts on a stationary cycle interspersed with 30-second rest periods. The subjects attempted to maintain 140 revolutions/min, which was chosen to result in fatigue. Creatine supplements resulted in subjects better able to maintain pedal speed measured during the last two seconds of each bout of exercise.

Although other trials of intermittent high intensity cycling showed creatine to be beneficial, several trials did not. Cooke et al took 12 untrained males and randomized them in a double-blind fashion to either 20 g of creatine a day or placebo for five days.8 Subjects were instructed to exercise as hard and fast as possible for 15 seconds on a stationary bicycle. After a 20-minute rest, a second trial was performed. No differences were seen after creatine supplementation in peak power, total work, or fatigue index compared to presupplement use. Also, no differences were seen between the placebo group or the creatine group.

Greenhaff et al studied 12 subjects in a randomized, double-blind trial of placebo or 20 g of creatine for five days in a protocol of five bouts of 30 maximal unilateral knee extensions separated by a one-minute rest period.9 After creatine, peak torque was statistically greater during all of the second through fourth bout and for one-third of the first and fifth bout. In a study of 17 patients with chronic congestive heart failure (EF < 40%), 20 g daily of creatine for 10 days improved stationary bicycle performance compared to baseline (P < 0.01) and compared to placebo (P < 0.05).10

Adverse Effects

No serious adverse event has been noted, although almost all studies lasted less than a week. Increases in the 24-hour urinary creatine, creatinine, and urate have been observed.11 In addition, with few exceptions, the studies included only healthy, young participants. Experts have cautioned that long-term use of high doses of creatine may damage kidneys. The Association of Professional Team Physicians has cautioned that creatine may cause dehydration and heat-related illnesses, cramps, reduced blood plasma volume, and electrolyte imbalances. The FDA has 20 reports of adverse events involving creatine, but there are no specifics available on those events to show any pattern of specific injuries or to detail the circumstances involved.

Creatine supplements result in an increase in body mass of 0.5-1 kg after five days of 20 g of creatine, and 1.8 kg after longer use. This is felt to be from water retention because high doses of creatine cause an acute decrease in urine volume. The long-term consequences of doses greater than 1 g daily are not known.

Drug Interactions

No specific drug interactions have been reported. However, cimetidine, trimethoprim, and probenecid are all known to interfere in the secretion of creatinine in the kidney. This could result in an increase in serum values of either the competing drug, creatinine, or both. In addition, athletes who take nonsteroidal antiinflammatory medications with creatine may stress their renal function.

Formulation/Dosage

Creatine supplements are available as pills, liquid, or powder. The powder form is the most common and is usually mixed up to four times daily with 4-8 ounces of orange or grape juice. Retail price varies greatly; 210 g will provide a 90-day supply if one follows the most common regimen (20 g/d for 5 days, then 2 g/d). Mail order prices range from $12 to $36.

Since studies have shown that combining creatine with carbohydrates will further increase muscle creatine compared to creatine alone,12 companies have marketed combination products (e.g., with dextrose) for a premium price. Many companies sell formulations that include other ingredients (e.g., vitamins, minerals, pyruvate, taurine, L-glutamine, and alpha-ketoglutarate). Some sample creatine formulations and prices are shown in the Table.

Table

Sample Creatine Prices and Formulations

Product Formulation Price
Mother Nature Creatine Monohydrate Powder 250 g $22
Source Naturals Creatine Tablets 1 g $26/100
Twin Creatine Fuel Plus 2 oz. Drink Mix packs $60/15
Weider Creatine Powder 100 g $19

Note: Most creatine advocates recommend initial "loading" dosages of 5 g four times daily for five days followed by maintenance doses of 5 g once or twice daily. Concentrations of creatine vary from product to product.

Conclusion

Although most studies have reported increased muscle mass and decreased fatigability with creatine use, the benefits were generally limited to high intensity intermittent activities. For the casual athlete, the improvements are likely inconsequential. For the trained athlete, creatine does appear to increase strength and performance in sports requiring rapid bursts of energy (e.g., soccer, football, basketball). This improvement may be due to increased strength and less susceptibility to fatigue. However, no benefit for aerobic activity has been seen; the weight gain with creatine may degrade performance. Also, 20-30% of people do not respond due to high baseline muscle creatine levels.

Chronic use of high doses of creatine, 5 or more g daily, should not be recommended until long-term safety is known. No one with impaired renal function should use creatine. High doses of creatine supplements should be discouraged for patients taking renally cleared medications until safety data are available.

References

    1. Sipila I, Rapola J, Simell O, et al. Supplementary creatine as a treatment for gyrate atrophy of the choroid and retina. N Engl J Med 1981;304:867-870.

    2. Harris RC, Soderlund K, Hultman E. Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clin Sci 1992;83:367-374.

    3. Greenhaff PL, Bodin K, Soderlund K, et al. Effect of oral creatine supplementation on skeletal muscle phosphocreatine resynthesis. Am J Physiol 1994;266:E725-E730.

    4. Casey A, Constantin-Teodosiu D, et al. Creatine ingestion favorably affects performance and muscle metabolism during maximal exercise in humans. Am J Physiol 1996;271:E31-E37.

    5. Hultman E, Soderlund K, Timmons JA, et al. Muscle creatine loading in men. J Appl Physiol 1996;81:232-237.

    6. Balsom PD, Harridge SDR, Soderlund K, et al. Creatine supplementation per se does not enhance endurance exercise performance. Acta Physiol Scand 1993;149:521-523.

    7. Balsom PD, Ekblom B, Soderlund K, et al. Creatine supplementation and dynamic high-intensity intermittent exercise. Scand J Med Sci Sports 1993;3:143-149.

    8. Cooke WH, Grandjean PW, Barnes WS. Effect of oral creatine supplementation on power output and fatigue during bicycle ergometry. J Appl Physiol 1995;78: 670-673.

    9. Greenhaff PL, Casey A, Short AH, et al. Influence of oral creatine supplementation of muscle torque during repeated bouts of maximal voluntary exercise in man. Clin Sci 1993;84:565-571.

    10. Gordon A, Hultman E, Kaijser L, et al. Creatine supplementation in chronic heart failure increases skeletal muscle creatine phosphate and muscle performance. Cardiovasc Res 1995;30:413-418.

    11. Vandenberghe K, Goris M, Van Hecke P, et al. Long-term creatine intake is beneficial during resistance training. J Appl Physiol 1997;83:2055-2063.

    12. Green AL, Hultman E, MacDonald IA, et al. Carbohydrate ingestion augments skeletal muscle creatine accumulation during creatine supplementation in humans. Am J Physiol 1996;271:E821-E826.