Creatine, the Next Ergogenic Supplement?


R B Kreider

Affiliation: Exercise & Sport Nutrition Laboratory, Human Movement Sciences and Education, University of Memphis, Memphis, Tennessee, USA
Acknowledgments: Paul Greenhaff (reviewer), Duncan MacDougall (reviewer), Will G Hopkins and Mary Ann Wallace (editing)
Correspondence: kreider.richard=AT=coe.memphis.edu (Richard B. Kreider, Ph.D.)
Reference: Kreider, R.B. (1998). Creatine, the next ergogenic supplement? In: Sportscience Training & Technology. Internet Society for Sport Science. http://www.sportsci.org/traintech/creatine/rbk.html

Summary. Creatine is used in muscle cells to store energy for sprinting and explosive exercise. Athletes can increase the amount of creatine in muscle by taking creatine supplements. Although some studies report no ergogenic effect, most indicate that creatine supplementation (e.g. 20 g per day for 5 to 7 days) increases sprint performance by 1-5% and work performed in repeated sprints by up to 15%. These ergogenic effects appear to be related to the extent of uptake of creatine into muscle. Creatine supplementation for a month or two during training has been reported to promote further gains in sprint performance (5-8%), as well as gains in strength (5-15%) and lean body mass (1-3%). The only known side effect is increased body weight. More research is needed on individual differences in the response to creatine, periodic or cyclical use of creatine, side effects, and long-term effects on endurance.
Reviewers' comments

Introduction

Creatine is an amino acid, like the building blocks that make up proteins. Creatine in the form of phosphocreatine (creatine phosphate) is an important store of energy in muscle cells. During intense exercise lasting around half a minute, phosphocreatine is broken down to creatine and phosphate, and the energy released is used to regenerate the primary source of energy, adenosine triphosphate (ATP). Output power drops as phosphocreatine becomes depleted, because ATP cannot be regenerated fast enough to meet the demand of the exercise. It follows that a bigger store of phosphocreatine in muscle should reduce fatigue during sprinting. Extra creatine in the muscle may also increase the rate of regeneration of phosphocreatine following sprints, which should mean less fatigue with repeated bursts of activity in training or in many sport competitions.

So much for the theory, but can you get a bigger store of creatine and phosphocreatine in muscle? Yes, and it does enhance sprint performance, especially repeated sprints. Extra creatine is therefore ergogenic, because it may help generate more power output during intense exercise. In addition, long term creatine supplementation produces greater gains in strength and sprint performance and may increase lean body mass. In this article I'll summarize the evidence for and against these claims. I'll draw on about 42 refereed research papers and four academic reviews to make conclusions regarding the ergogenic value of creatine supplementation. In addition, I'll provide 25 references to studies published in abstract form, which report the most recent preliminary findings on creatine supplementation.

Effects of Creatine Supplements on Muscle Creatine, Phosphocreatine, and ATP

The daily turnover of creatine is about 2 g for a 70 kg person. About half of the daily needs of creatine are provided by the body synthesizing creatine from amino acids. The remaining daily need of creatine is obtained from the diet. Meat or fish are the best natural sources. For example, there is about 1 g of creatine in 250 g (half a pound) of raw meat. Dietary supplementation with synthetic creatine is the primary way athletes "load" the muscle with creatine. Daily doses of 20 g of creatine for 5-7 days usually increase the total creatine content in muscle by 10-25%. About one-third of the extra creatine in muscle is in the form of phosphocreatine (Harris, 1992; Balsom et al., 1995).

Extra creatine in muscle does not appear to increase the resting concentration of ATP, but it appears to help maintain ATP concentrations during a single maximal effort sprint. It may also enhance the rate of ATP and phosphocreatine resynthesis following intense exercise (Greenhaff et al., 1993a; Balsom et al., 1995; Casey et al., 1996).

There is some evidence that not all subjects respond to creatine supplementation. For example, one study reported that subjects who experienced less of a change in resting muscle creatine (<20 mmol/kg dry mass) did not appear to benefit from creatine supplementation (Greenhaff et al., 1994). However, more recent studies indicate that taking creatine with large amounts of glucose increases muscle creatine content by 10% more than when creatine is taken alone (Green et al., 1996a; Green et al., 1996b). Consequently, ingesting creatine with glucose may increase its ergogenic effect.

Effects on Performance

Researchers first investigated the ergogenic effects of short-term creatine loading. In a typical study, a creatine dose of 5 g is given four times a day for five to seven days to ensure that muscle creatine increases. A control group is given a placebo (glucose or some other relatively inert substance) in a double-blind manner (neither the athletes nor the researchers doing the testing know who gets what until after the tests are performed). Most studies have shown that speed or power output in sprints--all-out bursts of activity lasting a few seconds to several minutes--is enhanced, typically by 5-8%. Repetitive sprint performance is also enhanced when the rests between sprints don't allow full recovery. In this case, total work output can be increased by 5-15%. There is also evidence that work performed during sets of multiple repetition strength tests may be enhanced by creatine supplementation, typically by 5-15%. In addition, one-repetition maximum strength and vertical-jump performance may also be increased with creatine supplementation, typically by 5-10%. The improvement in exercise performance has been correlated with the degree in which creatine is stored in the muscle following creatine supplementation, particularly in Type II muscle fibers (Casey et al., 1996).

Researchers have now turned their attention to longer-term creatine supplementation. In these studies, a week of creatine loading of up to 25 g per day is followed by up to three months of maintenance with reduced or similar dosages (2-25 g per day). Training continues as usual in a group given creatine and in a control group given a placebo. Greater gains are now seen in performance of single-effort sprints, repeated sprints, and strength (5-15%).

Table 1 at the end of this article lists the references to positive effects of creatine on performance. Theoretically, creatine may affect performance through one or more of the following mechanisms (Table 2): an increase in concentrations of creatine and phosphocreatine in resting muscle cells; an increased rate of resynthesis of phosphocreatine between bouts of activity; enhanced metabolic efficiency (lower production of lactate, ammonia, and/or hypoxanthine); and enhanced adaptations through higher training loads. Creatine supplementation during training may also promote greater gains in lean body mass (see Body Composition below).

Not all studies have reported ergogenic benefit of creatine supplementation (Table 3). In this regard, a number of equally well-controlled studies indicate that creatine supplementation does not enhance: single or repetitive sprint performance; work performed during sets of maximal effort muscle contractions; maximal strength; or, submaximal endurance exercise. What's more, one study reported that endurance running speed was slower, possibly because of an increase in body mass (Balsom et al., 1993b).

In analysis of these studies, creatine supplementation appears to be less effective in the following situations: when less than 20 g per day was used for 5 days or less; when low doses (2-3 g per day) were used without an initial high-dose loading period; in crossover studies with insufficient time (less than 5 weeks) to allow washout of the creatine; in studies with relatively small numbers of subjects; and when repeated sprints were performed with very short or very long recovery periods between sprints. It is also possible that subject variability in response to creatine supplementation may account for the lack of ergogenic benefit reported in these studies. In addition, there have been reports that caffeine may negate the benefit of creatine supplementation (Vandenberghe et al., 1996). Consequently, although most studies indicate that creatine supplementation may improve performance, creatine supplementation may not provide ergogenic value for everyone.

Body Composition

Although some studies have found no effect, most indicate that short-term creatine supplementation increases total body mass, by 0.7 to 1.6 kg. With longer use, gains of up to 3 kg more than in matched control groups have been reported (see Table 4 at the end of this article for references). For example, Kreider et al.(1998) reported that 28 days of creatine supplementation (16 g per day) resulted in a 1.1 kg greater gain in lean body mass in college football players undergoing off-season resistance/agility training. In addition, Vandenberghe et al. (1997) reported that untrained females ingesting creatine (20 g per day for 4 days followed by 5 g per day for 66 days) during resistance training observed significantly greater gains in lean body mass (1.0 kg) than subjects ingesting a placebo during training. The gains in lean body mass were maintained while ingesting creatine (5 g per day) during a 10-week period of detraining and in the four weeks after supplementation stopped.

Findings like these suggest that creatine supplementation may promote gains in lean body mass during training, but we don't yet understand how it works. The two prevailing theories are that creatine supplementation promotes either water retention or protein synthesis. More research is needed before we can be certain about the contribution each of these processes makes to the weight gain.

Side Effects

In studies of preoperative and post-operative patients, untrained subjects, and elite athletes, and with dosages of 1.5 to 25 g per day for up to a year, the only side effect has been weight gain (Balsom, Soderlund & Ekblom, 1994). Even so, concern about possible side effects has been mentioned in lay publications and mailing lists. Before discussing these possible side effects, it should be noted that they emanate from unsubstantiated anecdotal reports and may be unrelated to creatine supplementation. We must be careful to base comments regarding side effects of creatine supplementation on factual evidence, not speculation. But we must also understand that few studies have directly investigated any side effects of creatine supplementation. Consequently, discussion about possible side effects is warranted.

Anecdotal reports from some athletic trainers and coaches suggest that creatine supplementation may promote a greater incidence of muscle strains or pulls. Theoretically, the gains in strength and body mass may place additional stress on bone, joints and ligaments. Yet no study has documented an increased rate of injury following creatine supplementation, even though many of these studies evaluated highly trained athletes during heavy training periods. Athletes apparently adapt to the increase in strength, which is modest and gradual.

There have been some anecdotal claims that athletes training hard in hot or humid conditions experience severe muscle cramps when taking creatine, and the cramps have been attributed to overheating and./or changes in the amount of water or salts in muscle. But no study has reported that creatine supplementation causes any cramping, dehydration, or changes in salt concentrations, even though some studies have evaluated highly trained athletes undergoing intense training in hot/humid environments. In my experience with athletes training in the heat (e.g., during 2-a-day football practice in autumn), cramping is related to muscular fatigue and dehydration while exercising in the heat. It is not related to creatine supplementation. Nevertheless, athletes taking creatine while training in hot and humid environments should be aware of this possible side effect and take additional precautions to prevent dehydration.

Some concern has been raised regarding the effects of creatine supplementation on kidney function. The body seems to be able to dispose of the extra creatine without any problem (Poortmans et al., 1997). The extra creatine is eliminated mainly in the urine as creatine, with small amounts broken down and excreted as creatinine or urea. No study has shown that creatine supplementation results in clinically significant increases in liver damage or impaired liver function.

It has also been suggested that creatine supplementation could suppress the body's own creatine synthesis. Studies have reported that it takes about four weeks after cessation of creatine supplementation for muscle creatine (Vandenberghe et al., 1997) and phosphocreatine (Febbraio et al., 1995) content to return to normal. It is unclear whether muscle the content falls below normal thereafter. Although more research is needed, there is no evidence that creatine supplementation causes a long-term suppression of creatine synthesis when supplementation stops (Balsom, Soderlund & Ekblom, 1994; Hultman et al., 1996).

Does creatine supplementation have undiscovered long-term side effects? Trials lasting more than a year have not been performed, but creatine has been used as a nutritional supplement for over 10 years. Although long-term side effects cannot discounted, no significant short-term side effects other than weight gain have been reported. In addition, I am not aware of any significant medical complications that have been linked to creatine supplementation. Furthermore, creatine and phosphocreatine have been used medically to reduce muscle wasting after surgery and to improve heart function and exercise capacity in people with ischemic heart disease (Pauletto & Strumia, 1996; Gordon et al., 1995). Creatine supplementation may even reduce the risk of heart disease by improving blood lipids (Earnest, Almada & Mitchell, 1996; Kreider et al., 1998). On the basis of the available research, I consider creatine supplementation to be a medically safe practice when taken at dosages described in the literature.

Determining whether creatine supplementation has any short- or long-term side effects is an area receiving additional research attention. If there are side effects from long-term creatine supplementation, an important issue will be the liability of coaches, trainers, universities, and athletic governing bodies who provide creatine to their athletes. Anyone advising athletes to take creatine should make it clear that side effects from long-term use cannot be completely ruled out, and that the athletes do not have to take the supplements. It would be wise to have a formal policy for dosages to reduce the chances of athletes taking excessive amounts.

Ethics

Creatine supplementation is not banned, but is a nutritional practice that enhances performance nevertheless unethical? Anyone pondering this question should consider that creatine supplementation is a practice similar to carbohydrate loading, which is well accepted. Some are also concerned that creatine supplementation could cause a carryover effect, whereby athletes who have learned to take creatine are more likely to use dangerous or banned substances. Proper education among athletes, coaches, and trainers regarding acceptable and unacceptable nutritional practices is probably the best way to reduce any carryover.

How to Use Creatine

A typical loading regime for a 70-kg athlete is a 5-g dose four times a day for a week. Thereafter the dose can be reduced to 2 to 5 g per day in order to maintain elevated creatine content. This supplementation protocol will increase intramuscular creatine and phosphocreatine content and enhance high intensity exercise performance. There is now some evidence that taking glucose (100 g) with the creatine (5 to 7 g) increases the uptake of creatine into muscle (Green et al., 1996a; Green et al., 1996b). Consequently, I recommend that athletes take creatine with carbohydrate (e.g. with grape juice) or ingest commercially available creatine supplements that combine creatine with glucose. For athletes wanting to promote additional gains in lean body mass, I recommend 15 to 25 g per day for 1 to 3 months. Although many athletes cycle on or off creatine, no study has determined whether this practice promotes greater gains in fat free mass or performance than continuous use. More research is needed here.

Creatine supplements are good value. Creatine is now being sold for as little as US$30 per kg, or about $0.60 per day when taking 20 g per day. Popular sports drinks are more expensive.

Table 1. Positive Ergogenic or Anabolic Effects
of Creatine Supplementation

Type of performance

References

one repetition maximum and/or peak power

Becque, Lochmann & Melrose (1997); Birch, Noble & Greenhaff (1994); Earnest et al. (1995); Greenhaff et al. (1993b); Johnson, Smodic & Hill (1997); Kirksey et al. (1997); Kreider et al. (1996a); Stout et al. (1997);Vandenberghe et al. (1996); Volek et al. (1997); Ziegenfuss et al. (1997).

vertical jump

Bosco et al. (1997); Goldberg & Bechtel (1997); Stout et al. (1997).

multiple sets of maximal effort muscle contractions

Alamada et al. (1997); Bosco et al. (1997); Earnest et al. (1995); Greenhaff et al. (1993b); Hamilton-Ward et al. (1997); Johnson, Smodic & Hill (1997); Kreider et al. (1998); Kurosawa et al. (1997); Lemon et al. (1995); Vandenberghe et al. (1996); Vandenberghe et al. (1997); Volek et al. (1997).

single sprints lasting 6 to 30 s

Alamada et al. (1997); Balsom et al. (1995); Birch, Noble & Greenhaff (1994); Casey et al. (1996); Earnest et al. (1995); Ferreira et al. (1997); Greenhaff et al. (1993b); Grindstaff et al. (1997); Prevost, Nelson & Morris (1997); Stout et al. (1997); Ziegenfuss et al. (1997).

repetitive sprints (recovery 0.5-5 min)

Alamada et al. (1997); Balsom et al. (1993a); Balsom et al. (1995); Birch, Noble & Greenhaff (1994); Dawson et al. (1995); Earnest et al. (1995); Ferreira et al. (1997); Grindstaff et al. (1997); Harris et al. (1993); Kirksey et al. (1997); Kreider et al. (1998); Leenders et al. (1996); Prevost, Nelson & Morris (1997); Schneider et al. (1997); Ziegenfuss et al. (1997).

exercise lasting 1.5-5 min

Earnest, Almada & Mitchell (1997); Earnest, Stephens & Smith (1997); Harris et al. (1993); Jacobs, Bleue & Goodman (1997); Rossiter, Cannell & Jakeman (1996).

Table 2. How Creatine Enhances Performance

Proposed Mechanism

References

increased intramuscular creatine and phosphocreatine content

Balsom et al. (1995); Brannon (1997); Casey et al. (1996); Febbraio et al. (1995); Green et al. (1996a); Green et al. (1996b); Greenhaff et al. (1993a); Greenhaff et al. (1994); Harris, Soderlund & Hultman (1992); Hultman et al. (1996); Kurosawa et al. (1997); Lemon et al. (1995); Myburgh et al. (1996); Rossiter, Cannell & Jakeman (1996); Ruden et al. (1996); Vandenberghe et al. (1996); Vandenberghe et al. (1997).

greater resynthesis of phosphocreatine

Balsom et al. (1995); Casey et al. (1996); Greenhaff et al. (1993a); Lemon et al. (1995); Ruden et al. (1996); Vandenberghe et al. (1996).

increased metabolic efficiency

Balsom et al. (1993a); Balsom et al. (1995); Birch, Noble & Greenhaff (1994); Casey et al. (1996); Greenhaff et al. (1993b); Nelson et al. (1997).

enhanced adaptations with training

Alamada et al. (1997); Becque, Lochmann & Melrose (1997); Earnest et al. (1995); Ferreira et al. (1997); Goldberg & Bechtel (1997); Grindstaff et al. (1997); Kirksey et al. (1997); Kreider et al. (1997b); Kreider et al. (1998); Kreider et al. (1996a); Leenders et al. (1996); Stout et al. (1997).

Table 3. Negative or No Effect of Creatine Supplementation

Type of performance

References

one repetition maximum

Hamilton-Ward et al. (1997)

work performed during low intensity muscle contractions

Kurosawa et al. (1997)

work performed during high intensity muscle contractions

Thompson et al (1996)

single sprints lasting 6-60 s

Burke, Pyne & Telford (1996); Dawson et al. (1995); Goldberg & Bechtel (1997); Odland et al. (1997). Ruden et al. (1996).

repetitive sprints (recovery 30 s to 25 min)

Barnett, Hinds, & Jenkins (1996); Cooke & Barnes (1997); Cooke, Grandjean & Barnes (1995); Mujika et al. (1996); Redondo et al. (1996).

exercise lasting >60 s

Burke, Pyne & Telford (1996); Febbraio et al. (1995); Godly & Yates (1997); Myburgh et al. (1996); Terrilion et al. (1997).

Table 4. Effects of Creatine on Body Mass

Effect

References

short-term increase in total body mass

Balsom et al. (1993a); Balsom et al. (1993b); Balsom et al. (1995); Green et al. (1996b); Greenhaff et al. (1994); Lemon et al. (1995); Redondo et al. (1996); Vandenberghe et al. (1996); Vandenberghe et al. (1997); Volek et al. (1997).

no short-term increase in body mass

Earnest, Almada & Mitchell (1996); Godly and Yates (1997); Grindstaff et al. (1997); Hamilton-Ward et al. (1997); Redondo et al. (1996); Terrilion et al. (1997).

long-term increase in total body mass

 

Becque, Lochmann & Melrose (1997); Earnest et al. (1995); Goldberg & Bechtel (1997); Kirksey et al. (1997); Kreider et al (1997a); Kreider et al (1997b); Kreider et al. (1996a); Kreider et al. (1996b); Sipila et al. (1981); Stout et al. 1997; Vandenberghe et al. (1997).

increase in lean body mass

Becque, Lochmann & Melrose (1997); Earnest et al. (1995); Kirksey et al. (1997); Kreider et al (1997a); Kreider et al (1997b); Kreider et al. (1996a); Kreider et al. (1996b); Stout et al. (1997); Vandenberghe et al. (1997); Ziegenfuss et al. (1997).

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