In this paper the evidence for the effectiveness of the food supplement creatine in improving sports performance is considered
Athletes are always searching for nutritional supplements that will give them sufficient advantage over fellow competitors to ensure a position on the victory podium. To a great extent this accounts for the reports of illegal drug taking in sport. The secret, of course, is to find a product that is effective in improving performance, yet is not banned by the International Olympic Committee. Long-term safety would not seem be the prime concern for many athletes.
There have been claims for the performance enhancing qualities of many dietary supplements, collectively referred to as ergogenic aids. Within recent years a new arrival - creatine - has appeared. Many community pharmacists selling health foods and supplements will have been consulted on the potential benefits and dangers of using creatine to improve sporting performance.
The biggest ever survey of British sportsmen and women, organised by the Independent newspaper in 1998,1 revealed widespread use of creatine, which is claimed to have similar performance enhancing effects to those of steroids. More than 300 elite performers responded to a questionnaire about drug use in British sport. Nearly 57 per cent said they had taken creatine, which is presently marketed legally by mail order and over the counter in health shops. Among rugby league players and weight lifters creatine usage was 100 per cent. In America the public race between two baseball players to achieve a record number of home runs drew admissions from both men that they had consumed creatine.
The enthusiastic endorsement of creatine by high profile professional athletes has raised its popularity among teenagers and amateurs. It has also prompted questions about the long-term safety of the supplement.
Creatine (or methylguanidine-acetic acid) is a physiologically active substance indispensable to muscle contraction. The normal daily intake of creatine is less than 1g, obtained mainly from meat and fish and other animal products. However, the estimated daily requirement for the average individual is double that amount. The balance is produced in the body mainly by the kidneys together with smaller amounts from the liver and pancreas. The intake of exogenous creatine in the diet appears to play a role in the control of endogenous creatine synthesis by means of a feedback mechanism.2 Creatine is formed from three amino acids - argenine, glycine and methionine - and it reaches the muscle cells by an active membrane transport system.
There is a store of 120–140g of creatine in the body of which 98 per cent is stored in muscle. Approximately 30 per cent of muscle creatine is free, the balance being bound as phosphocreatine, which is replenished at a rate of 20mg/kg/day following its rapid degradation in the Lohman reaction3 to creatine. Phosphocreatine is present in resting muscle in a concentration three to four times that of adenosine triphosphate (ATP), the immediate energy source for muscle contraction.4 If cellular ATP concentration falls too far, fatigue occurs.
The rate of ATP hydrolysis to adenosine diphosphate (ADP) and free phosphorus is set by the power output of the muscles, ie, the intensity of the exercise. Regeneration of ATP at a rate close to that of its hydrolysis is vital if fatigue is to be delayed. Indeed, a decline in the rate of resynthesis of ATP as a result of depletion of phosphocreatine is recognised as a possible cause of reduction in muscle power in maximal intensity exercise.5
In the regeneration of ATP, transfer of the phosphate group from phosphocreatine is catalysed by the enzyme creatine kinase, resulting in the restoration of ATP and the release of free creatine.
The biochemical processes during exercise may be summarised thus:
ATP —> ADP + P
PCr + ADP + H+ —> ATP + Cr
The creatine kinase reaction is extremely rapid and since the muscle phosphocreatine concentration can fall to almost zero it is likely to contribute significantly to the energy supply required for short bursts of high intensity exercise. During the recovery stage following exercise, the creatine kinase reaction is reversed using oxygen resulting from a metabolic process in the mitochondria:
Cr + ATP —> PCr + ADP
ADP + P + metabolism —> ATP
In high intensity exercise, glycolysis will result in the formation of pyruvate at a rate higher than that at which it can be removed by oxidative metabolism. This leads to a build up of lactate within the muscle. Muscle pH falls as a result of the glycolysis and is thought to be involved in the development of fatigue. The breakdown of phosphocreatine acts as a buffer mechanism within the cell delaying the point at which a critically low pH is reached. An increased availability of phosphocreatine for breakdown may increase the buffering capacity in the muscles.
As stated above, during brief intense anaerobic actions like sprinting or weightlifting, phosphocreatine regenerates ATP to provide the energy necessary to maintain muscle contractions.
What evidence is there that taking creatine orally does in fact increase its resting levels?
Studies have shown the concentrations of phosphocreatine and free creatine in resting human skeletal muscle to vary widely. Several factors may be responsible, including dietary creatine uptake6 and relative amounts of slow-twitch and fast-twitch fibres. The fast-twitch fibres have a higher total creatine content than the slow fibres. For reasons not yet understood, females appear to have slightly higher resting levels of creatine than males. The starting point therefore is far from fixed.
Most of the studies have been well controlled, but crossover designs are impractical because of the long washout period from the muscle. When high doses are taken over a period of four to six days, the muscle creatine content will remain elevated for several weeks. If athletes are used as subjects, the increased training loads that result after taking creatine make it difficult to interpret results from crossover trials in which placebo was administered as the second treatment.4 As a result of these experimental difficulties, most of the reported studies have used matched groups of subjects.
Harris et al showed in a comprehensive trial that ingestion of 1g or less of creatine had a negligible effect on the circulating creatine concentration, whereas doses in the region of 5g resulted in an approximately 15-fold increase.7 Repeated feeding of 5g of creatine four times a day for four to five days caused a marked increase in total creatine content of the quadriceps femoris muscle. An increase in muscle creatine content was apparent within two days of starting this regimen and the increase was greatest in those subjects with a low initial level. In later work, Harris et al used a creatine dose of 30g per day for six days and compared matched treatment and placebo groups.8 The subjects were trained runners, and two different exercise tests were conducted on separate days. One test comprised four 300m runs with a four-minute rest period between each run, and the other test comprised four 1,000m runs with three-minute rest periods. At the 300m distance there was a significant improvement only on the last outing, while for the longer distance a mean improvement of 13 seconds was achieved on each of the four runs.
Greenhaff et al showed that 20g of creatine administered over five days caused an increase in total creatine of 20 to 25 per cent, of which 20 per cent was available as phosphocreatine.9 This innovative experiment involved an hour of hard exercise per day using one leg which produced an increase in muscle creatine in the exercised leg but not in the other leg.
Peyrebrune et al demonstrated that ingesting 9g of creatine per day for five days could improve swimming performance in elite competitors during repeated sprints, but appeared to have no effect on a single, 50-yard sprint.10
The effect of creatine was also studied by Thompson et al.11 Studies were performed on a group of 10 female swimmers before and after a six-week period of training during which they were randomised to take either 2g of creatine daily (the manufacturer's recommended dose) or placebo. Calf muscle metabolism was studied in resting muscle, during plantar flexion exercise (10–15 minutes) and during recovery from exercise. It was concluded that oral creatine supplementation at the daily dosage chosen had no effect on muscle creatine concentration. It is probable that the daily dose levels were too low for any effect to be noticed. Further, the exercise was submaximal. No beneficial effect of creatine supplementation was reported by Odland et al using a cross over design involving control, placebo and creatine supplementation.12 A daily dose of 20g of creatine was administered for three days. Neither creatine nor phosphocreatine levels were enhanced. There may be two main reasons for this result. Only a single exercise test was used in this study, unlike in studies by other workers, who generally used multiple bouts of activity, and the total amount of creatine administered was less than in other research.
Few studies of creatine supplementation in strength-trained athletes or in prolonged exercise are to be found in the literature. The object of a study by Engelhardt et al was to investigate the changes in creatine and creatine concentration after supplementation of low creatine dosages in 12 regional class triathletes.3 The endurance athlete has to use anaerobic exercise in his or her sport to a varying degree. It may influence performance when intermediate or finishing bursts of energy are needed. The authors concluded that doses of 6g of creatine daily had positive effects on short term exercise included in an aerobic endurance event.3 Unfortunately, only a small number of subjects were tested, and the trial was not double blinded.
Earnest et al investigated the influence of creatine supplementation on the muscular power and strength indices in 10 experienced, weight-trained male subjects.13 Three series of high-intensity, anaerobic type muscular work bouts were used. Subjects received, in double blind fashion, either glucose-based placebo or 14 days of creatine supplementation similar to that used in earlier studies by Harris et al6 and Greenhaff et al.7 Higher work outputs were observed in the creatine group, and these were explained in terms of increases in intramuscular phosphocreatine stores. An associated weight gain was not so easily explained, although an osmetic effect is likely.
Generally, elite performers do not seem to have positive outcomes from taking creatine. Balsom et al demonstrated using highly trained runners as subjects that ingesting creatine for six days was of no use for endurance exercise performance.14 Their subjects showed no improvement during a supramaximal treadmill run to exhaustion and significantly slower performance during a six-kilometre road run. Increased body weight, possibly due to increased body water, may be in part responsible for this reduced performance.
Using a double-blind, placebo-controlled design involving 32 elite male and female swimmers from the Australian national team, Burke et al reported that oral creatine (20g per day for five days) did not enhance performance in maximal single effort swim sprints of 25m and 50m each interspersed with a 10-minute recovery period.15
A similar negative outcome was observed by Mujika et al who studied the effects of five days of creatine or placebo supplementation on 25m, 50m and 100m performance in elite swimmers performing their best stroke.16 Swimmers showed a tendency towards increased 25m and 50m times. The authors hypothesised that the swimmers' increased body weight was the reason.
There is a consensus in the literature to suggest that oral creatine supplementation of 20 to 30g per day (equivalent to eating about 5kg of raw steak) for five to six days ("rapid loading") can improve performance in high-intensity, short-term exercise by increasing the resting concentrations of creatine and phosphocreatine, and by improving the rate of phosphocreatine and ATP resynthesis in skeletal muscle.
These higher muscle levels can be maintained by ingesting 2g per day thereafter. A similar, but slower 20 per cent rise in muscle creatine levels can be achieved in one month by ingesting 3g per day ("no-load method").9
There are several important factors to consider when taking creatine:17
The matter of long-term effects and the possibility of adverse reactions are beginning to cause considerable concern, particularly as the death of three American wrestlers was linked to its use (although it has been stated that the men were taking other ergogenic products concurrently). Substantial renal dysfunction has been reported in a patient who had taken creatine supplement to augment his pre-season soccer-training regime.18 A complication could arise with anyone who is taking supplemental creatine, and for some other reason has urinary creatine measured. The increased levels could lead a doctor to suspect (wrongly) that the patient has renal impairment. Pharmacists should ensure that individuals are aware of this fact.
Creatine supplementation may cause an electrolyte imbalance, leading to a predisposition to dehydration and heat-related illness. There are no reliable scientific data on possible adverse reactions at present.
Should the supplement be banned on the grounds of an ergogenic effect, as is the case with caffeine? Sports bodies will no doubt consider the matter in the foreseeable future. Already the Irish Rugby Union is considering imposing sanctions on schools that endorse creatine use to boost muscle efficiency.
Studies involving highly trained elite athletes performing single sport specific sprint activities have not yielded positive results for creatine supplementation. The answer to the question posed at the beginning of this paper as to whether athletes can consider creatine to be a wonder supplement rather depends on their individual acceptance of the trade off between the risk and benefit of taking it. Research evidence shows that it appears to work for some athletes but not for others. There are, as yet, uncharted side effects. There are ethical considerations, as with all chemical aids. "Use it judiciously," would seem to be good advice.
Dr Kayne is a community pharmacist in Glasgow. Correspondence to 20 Main Street, Busby, Glasgow G76 8DU (e-mail SKayne9665@cs.com)