Creatine: The Ergogenic / Anabolic Supplement

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Mesomorphosis, September 1998 (Volume 1, Number 4)

by Richard B. Kreider, PhD, FACSM
rkreider@memphis.edu 

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• What is Creatine?
• How Does Creatine Work?
• Does Creatine Enhance Exercise Performance?
  • Maximal Strength/Power
    • Multiple Sets of Maximal Effort
    • Muscle Contractions
    • High Intensity Sprint Exercise
  • Endurance Exercise
    • Studies Reporting No Ergogenic Benefit
• Does Creatine Affect Muscle Mass?
• Is Creatine Safe?
  • Clinical Effects of Creatine Supplementation
  • Side Effects
• Summary and Conclusions
• References

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Overview

Scientific studies indicate that creatine supplementation is an effective and safe nutritional strategy to promote gains in strength and muscle mass during resistance-training. Moreover, that creatine supplementation may be an effective alternative to other less effective and/or potentially dangerous nutritional and pharmacological strategies that athletes have used in an attempt to increase strength and muscle mass during training. Consequently, creatine has become one of the most popular nutritional supplements for resistance-trained athletes and body builders. Yet despite the scientific evidence, there has been a significant amount of controversy about creatine reported in the popular media. This article will examine what we do and don’t know about creatine and whether concerns about side effects reported in the popular media have any merit.

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What is Creatine?

Creatine is a naturally occurring amino acid which is derived from the amino acids glycine, arginine, and methionine. The body stores creatine in both free and phosphorylated forms. The average sized person (70 kg) stores about 120 g of creatine.^{7,17,49,59,60,77,121} Most of the creatine is stored in skeletal muscle (95%) primarily as phosphocreatine (66%) while the remaining amount of creatine is found in the heart, brain, and testes.^{7,17,49,60,121} The normal daily requirement for creatine is about 1.6% of the total creatine pool (about 2 to 3 g/d for a 70 to 100 kg individual). About half of the daily needs of creatine are typically obtained from the diet primarily from meat, fish, and animal products. For example, there is about 1.4 to 2.3 g of creatine per pound of meat (beef, pork) or fish (tuna, salmon, cod). Herring contains about 3 to 4.5 g of creatine per pound. Creatine can also be obtained by supplementing the diet with pharmacological grade synthetic creatine. The most popular and economical form of synthetic creatine is creatine monohydrate (creatine plus one molecule of water).

When dietary availability of creatine is insufficient to meet daily needs, the remaining creatine is synthesized from the amino acids glycine, arginine and methionine primarily in the liver, kidney and pancreas (refer to Figure 1).^7,17,49 This first involves the reversible transfer of an amidine group from arginine to glycine to form guanidinoacetic acid. This is then followed by an irreversibly transfer of a methyl group from S-adenosylmethionine to guanidinoacetic acid forming creatine. When dietary availability of creatine is low, endogenous synthesis of creatine is increased to maintain normal levels. On the other hand, when dietary availability of creatine is increased, endogenous creatine synthesis is temporarily suppressed. ^7,17,49

See Figure 1.

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How Does Creatine Work?

The energy for all out maximal effort exercise lasting up to 6 to 8 seconds is primarily derived from limited stores of adenosine triphosphate (ATP) in the muscle. In this regard, the phosphate from ATP is cleaved off liberating energy for muscle contraction. During explosive exercise, the phosphate from phosphocreatine (PCr) stored in the muscle is also cleaved off to provide energy for resynthesis of ATP. This allows the ATP pool to be turned over several dozen times during an all out maximal effort exercise bout lasting 6 to 8 seconds. Additionally, the energy derived from the breakdown of PCr during recovery helps restore the ATP depleted during maximal effort explosive exercise.

Creatine supplementation has been suggested as a means to "load" the muscle with creatine and PCr in a similar way that endurance athletes "load" their muscle with carbohydrate.^59,60,121 Loading the muscle with creatine and PCr would theoretically serve to improve the ability to produce energy during high intensity exercise as well as improve the speed of recovery. Theoretically, this would help an athlete perform more work during a single bout of high intensity exercise and recover faster between multiple sets of high intensity exercise.

Well, so much for the theory. There are lots of supplements sold to athletes that sound great in "theory". The bottom line for the athlete is does it work? Is the supplement safe? And, is the supplement worth the money? Unlike most supplements you find at your local health food store, there has been a great deal of research investigating the effects of creatine supplementation on muscle energy production and exercise performance. If fact, with the exception of carbohydrate, creatine has been the most extensively studied nutrient sold to athletes.

Studies investigating the effects of dietary creatine supplementation actually began in the early 1920s.¹⁷ Although initial studies reported some ergogenic benefit, elite athletes didn’t begin using creatine as a nutritional supplement until the 1960s (particularly in the Eastern block countries of the former Soviet Union). In the mid- to late 1980s, creatine became a popular nutritional supplement among elite athletes in Europe and Great Britain. However, its widespread used among the general athletic communities didn’t occur until the early to mid 1990's when synthetic creatine was marketed in the U.S. more affordably.^59,60,121

As of this writing, there have been about 70 original research articles published in peer-reviewed journals on creatine supplementation with another 50 or so papers presented in the last few years at various scientific meetings. These studies indicate that short-term creatine "loading" (15 to 30 g/d or 0.3 g/kg/d for 5 to 7-d) increases total creatine content (TCr) by 15 to 30% and PCr stores by 10 to 40%.^{8,11,15,16,32,38,39,40,42,43,47,50,69,70,72,79, 91,92,115} For example, Harris and coworkers ⁴⁷ reported that ingesting 20 to 30 g/d of creatine for 5-, 7- and 10-d or on alternate days for 21-d increased TCr by 20% (127 to 149 mmol/kg dry mass) and PCr by 36% (67 to 91 mmol/kg dry mass). Likewise, Balsom and associates⁸ reported that creatine supplementation (20 g/d for 6-d) increased muscle TCr by 18% (129 to 152 mmol/kg dry mass). An alternative strategy of increasing muscle creatine content is to ingest small amounts of creatine per day (3 g/d) for 28-d. This results in a more gradual increase in TCr and PCr concentrations over time.⁵⁰ Studies show that the greatest amount of creatine uptake occurs during the first 3- to 5-d of ingesting loading doses.^47,50 The elevated levels of muscle TCr and PCr can be maintained thereafter by ingesting 2 to 5 g/d.^50,115 Following cessation of creatine supplementation, TCr and PCr levels return toward baseline levels in 28- to 35-d.^32,72,115

Although all studies have reported increases in muscle TCr and PCr levels following creatine loading (i.e., 20 g/d for 5-d), there is some evidence that not all individuals respond as well to creatine loading as others (i.e., observe less than a 20 mmol/kg dry mass increase in TCr levels). Further, that "non-responders" experience less of an improvement in exercise performance following creatine supplementation.^43,47 In this regard, studies suggest that some subjects (20 to 30%) only increase TCr and PCr levels by 5 to 15% in response to creatine loading (20 g/d for 5-d) and that these subjects experience less of an improvement in exercise capacity than subjects experiencing greater than 20% increase in TCr and PCr. This "non-responder" phenomenon has been suggested to be due to possible differences in storage rates or initial creatine content among people. However, more recent studies ^39,40 indicate that if you ingest creatine (20 g/d) with large amounts of glucose (380 g/d) during the first 5-d loading period, muscle creatine content was increased by 10% more than when creatine was ingested alone (143 to 158 mmol/kg dry mass). This allowed all subjects to experience large increases in muscle creatine content and performance. Additionally, these investigators found that when creatine was ingested with glucose, glycogen content was increase by 18% more than when glucose was ingested alone (418 to 489 mmol/kg dry mass). While this change was not significantly different, gains in glycogen were significantly correlated with gains in TCr suggesting that the increases in glycogen observed were at least in part due to creatine. This is the reason why it is recommended that athletes ingest creatine with glucose or fruit juice. Figure 2 presents the average changes in TCr and PCr reported in the literature in response to creatine supplementation with and without glucose.

See Figure 2.

Since creatine supplementation can increase intramuscular PCr concentrations, creatine supplementation would theoretically enhance the availability of energy during explosive, high-intensity exercise bouts and/or enhance the ability to recover from intense exercise. For this reason, a number of studies have evaluated the effects of creatine supplementation on ATP and PCr concentrations during and following high-intensity exercise.^{8,15,16,32,42,43,72,115} These studies indicate that creatine supplementation does not appear to alter pre-exercise ATP concentrations.^32,47 However, the elevated PCr concentrations serve to maintain ATP concentrations to a greater degree during maximal effort high intensity exercise.¹⁶ In addition, creatine supplementation appears to enhance the rate of ATP and PCr resynthesis following intense exercise.^{8,15,16,32,42,43,72,115} Since resistance-training involves performance of multiple sets of moderate to high intensity exercise, creatine supplementation would theoretically allow a weight lifter/body builder to increase work output during multiple sets of resistance-exercise leading to greater gains in strength and/or muscle mass.

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Does Creatine Enhance Exercise Performance?

Most studies (about 70 to 80%) which have investigated the ergogenic value of short-term (5 to 7-d) and/or long-term (7 to 140-d) creatine supplementation (20 to 25 g/d for 5 to 7-d and 2 to 25 g/d thereafter) have reported that creatine supplementation significantly increases strength/power, sprint performance, and/or work performed during multiple sets of maximal effort muscle contractions. The improvement in exercise capacity has been attributed to increased TCr and PCr content .^{8,15,16,32,39,40,42,43,47,50,69,72,79,91,92,114,115,116} particularly in type II muscle fiber,^16,79 greater resynthesis of PCr, ^{8,16,42,72,92,115} improved metabolic efficiency, ^{5,8,16,12,44,80} and/or an enhanced quality of training promoting greater training adaptations.^{1,12,33,37,45,56,57,62-65,73,84,91,104} The following analysis overviews some of the literature reporting ergogenic benefits of creatine supplementation. Additionally, Table 1 summarizes results of studies evaluating the ergogenic value of creatine supplementation. For a more detailed analysis of these and other studies, see Tables 1 through 3 in a review recently published ⁵⁹ in the Journal of Exercise Physiology Online.

Maximum Strength/Power

For a weight lifter/body builder, gains in strength/power are often accompanied by muscle hypertrophy. Consequently, ingesting a nutritional supplement which can promote strength gains during training may be particularly beneficial. Studies indicate that creatine supplementation during training can increase gains in one repetition maximum (1RM) strength and/or power.^{10,12,24,28,29,38,44,54,56,57,65,74,76,89,94,115,116,117,120,124} For example, Earnest and associates ²⁹ reported that 28-d of creatine supplementation (20 g/d for 28-d) during resistance-training promoted a significantly greater gain in 1RM bench press performance (8.2 kg) compared to subjects ingesting a placebo during training (-2.9 kg). Likewise, Vandenburghe and colleagues ¹¹⁶ reported that creatine supplementation (20 g/d for 4-d followed by 5 g/d for 66-d) promoted a 20 to 25% greater gain in 1RM strength in untrained women participating in a 70-d resistance-training program than subjects receiving a placebo. Furthermore, the gains in strength observed were maintained in subjects ingesting creatine during a 70-d detraining period. These findings indicate that creatine supplementation during resistance-training promotes significantly greater gains in strength.

While it is understandable that if creatine allows an athlete to train harder that athletes may get stronger over time, studies also indicate that short-term creatine supplementation may enhance peak power.^{12,24,38,44,54,57,124} For example, Dawson and coworkers ²⁴ reported that creatine supplementation (20 g/d for 5-d) significantly increased peak power during the first set of 6 x 6-s sprints. Birch and colleagues ¹² reported that creatine supplementation (20 g/d for 5-d) significantly increased peak power output (8%) during three sets of 30 maximal effort cycling sprints. Moreover, short-term creatine supplementation has been reported to increase peak concentric and eccentric power ⁵⁴ as well as vertical jump performance.^13,37,104 These findings are interesting in that peak power generated during a single explosive exercise (e.g. 1 RM) is not greatly dependent on the amount of ATP and PCr in the muscle. To increase power, one has to generate more force in a shorter period of time which usually occurs in response to muscle hypertrophy and/or enhanced neural adaptations to training. Consequently, since the availability of ATP and PCr are not limiting factors to an explosive 1RM, one would not expect short-term creatine supplementation to improve peak power. Yet, several studies indicate that short-term creatine supplementation can increase peak power and/or 1RM strength. These findings have led researchers to wonder if short-term creatine supplementation may affect the peripheral nervous system.

Multiple Sets of Maximal Effort Muscle Contractions

One of the potentially most beneficial effects of creatine supplementation for the weight lifter/body builder is that creatine supplementation has been reported to increase the amount of work performed during a series of maximal effort muscle contractions. ^{1,3,13,29,38,44,46,54,64,69,72,98,115,116,117,122} For example, Bosco et al ¹³ found that creatine supplementation (20 g/d for 5-d) significantly increased jump performance during two 15-s jump tests separated by a 15-s rest recovery. Volek and colleagues ¹¹⁶ reported that creatine supplementation (25 g/d for 7-d) resulted in a significant increase in the amount of work performed during five sets of bench press and jump squats in comparison to a placebo group. Moreover, Earnest and associates ²⁹ found that creatine supplementation (20 g/d for 28-d) significantly increased bench press total lifting volume (43%) when performing a 70% of 1 RM bench press repetition test. Finally, Kreider et al.⁶⁴ reported creatine supplementation (15.75 g/d for 28-d) promoted a 41% greater gain in combined bench press, squat, and power clean lifting volume. These findings suggest that creatine supplementation may enhance the ability to perform sets of multiple effort muscle contractions thus serving to increase the quality of workouts.

Sprint/High-Intensity Performance

Creatine supplementation has also been reported to improve single effort ^{1,8,12,16,28,29,33,44,45,70,87,94,104,123} and/or repetitive sprint performance ^{1,5,8,12,24,27,29,31,33,48,55,57,64,71,73,74,85,91,109,121,123} particularly in sprints lasting 6 to 30-s with 30-s to 5-min of rest recovery between sprints. For example, Birch et al ¹² reported that creatine supplementation (20 g/d for 5-d) significantly increased work performed during the first of 3 x 30-s cycle ergometer sprints with 4-min recovery between sprints. Grindstaff and coworkers ⁴⁵ reported that creatine supplementation (21 g/d for 9-d) significantly improved 3 x 100-m swim performance with 60-s rest recovery between sprints. Moreover, Kreider and associates ⁶⁴ reported that 28-d of creatine supplementation (15.75 g/d) during off-season football resistance/agility training resulted in significant improvements in repetitive sprint performance during the first five of 12 x 6-s sprints with 30-s rest recovery between sprints. Finally, Earnest and colleagues ²⁹ reported that creatine supplementation (20 g/d for 28-d) increased work performed during 3 x 30-s cycle ergometer sprints with 5-min rest recovery between sprints. While not all studies indicate that creatine supplementation improves single and/or repetitive sprint performance (see discussion below), these studies suggest that creatine supplementation may improve single and/or repetitive sprint performance.

Although exercise involving the ATP-PC energy system (i.e., high-intensity single and/or repetitive sprint performance lasting up to 8 seconds) would theoretically receive the most benefit from creatine supplementation, some investigators have studied whether creatine supplementation would affect high-intensity exercise performance lasting 60-s to 10-min in duration.^{14,26,27,30,32,48,97,108} The rationale for this is that often the latter portions of high-intensity exercise performance lasting 60-s to 10-min often involves all out sprint performance. Consequently, if creatine loading enhances sprint performance, it may provide some ergogenic benefit in longer events which also require sprint performance at the end of the events. There are several studies supporting this theory. In this regard, Harris and coworkers ⁴⁸ reported that sprint performance during a series of 300- and 1,000-m runs were significantly improved with creatine supplementation (30 g/d for 6-d). Earnest and colleagues^26,27 and Smith et al. ⁹⁷ found that creatine supplementation significantly increased high intensity exercise performance lasting up to 600-s in duration. Moreover, Rossiter et al.⁹¹ reported that creatine supplementation (0.25 g/kg/d for 5-d) significantly decreased time to perform a 1,000-m rowing time trial by 2.3-s in an event lasting about 210-s in comparison to a placebo group. Finally, Jacobs and associates⁵² reported that creatine supplementation significantly increased time to exhaustion by 8% (130 to 141-s) following 5-d of creatine supplementation (20 g/d) as well as following 7-d cessation of supplementation by 7% (139-s). Although additional research is necessary, these findings suggest that creatine supplementation may provide some ergogenic benefit in events lasting up to 10-min. Collectively, these findings suggest that if your involved in more than just weight lifting/body building (as most resistance-trained athletes are), creatine may improve your ability to sprint, recover from sprints, and perform high-intensity exercise lasting up to 10-min in duration.

Endurance Performance

Although the ATP-PC energy system is not highly involved in submaximal endurance exercise performance, several studies have evaluated the effects of short-term creatine supplementation on submaximal endurance exercise performance.^6,31,36,79 These studies indicate that short-term creatine supplementation does not appear to improve submaximal exercise performance. In fact, Balsom and colleagues ⁶ reported that 6-km run performance may be negatively affected theoretically due to an increase in body mass. Consequently, creatine supplementation is generally not recommended for endurance athletes.

However, it should be noted that no long-term studies have been conducted on the effects of creatine supplementation in endurance athletes. It is my view that there may be some potential benefits of creatine supplementation for endurance athletes that warrant additional research. In this regard, creatine supplementation has been reported to increase repetitive sprint performance, muscle mass, and enhance glycogen uptake when creatine is ingested with large amounts of glucose. Consequently, creatine supplementation may help an endurance athlete by improving interval performance capacity during training, maintain muscle mass during training, and/or serve as an effective way to load the muscle with glycogen. Additionally, creatine supplementation has been shown to help athletes tolerate training to a greater degree. Over time, this may lead to improved endurance performance capacity and/or a reduction in the incidence of overtraining.

Studies Reporting No Ergogenic Benefit

Although most studies (about 70 to 80%) have reported statistically significant improvement in exercise performance in response to short and/or long-term creatine supplementation, some well-controlled studies have reported no ergogenic benefit from creatine supplementation (see table 2). The reason for the lack of ergogenic effect of creatine supplementation observed in these studies is not clear. However, it is possible that individual variability in response to creatine supplementation previously discussed may account for the lack of ergogenic benefit reported in these studies.^43,47 It is also possible that differences in experimental design may account for some of the differences in results observed. In this regard, creatine supplementation appears to be less ergogenic when supplementation regimens are less than 20 g/d for 5-d ^9,53,92,81 or involve low-dose supplementation regimens (2 to 3 g/d) without an initial higher dose loading period.^44,52 In addition, studies which used relatively small sample sizes (e g., < 6 subjects per group) or employed crossover experimental designs with less than a 5-wk washout period between trials typically have found no ergogenic benefit.^32,72,81,92 Creatine supplementation may also be less ergogenic depending on the amount of work performed and rest recovery observed between repetitive exercise trials. Several studies report that creatine supplementation does not effect performance in sprints lasting 6- to 60-s when prolonged recovery periods (5- to 25-min) are observed between sprint trials.^14,22,78,90 Finally, short-term creatine supplementation does not appear to enhance endurance exercise.^31,36,79 Consequently, although most studies indicate that creatine supplementation may improve performance, creatine supplementation may not provide ergogenic value for everyone.

Does Creatine Affect Muscle Mass?

So creatine may improve your ability to train harder and recover faster from multiple sets during your workouts. Does it really increase muscle mass? If so, are gains modest or impressive? Is creatine really an nutritional alternative to other anabolic agents or just another overly hyped supplement?

Most studies indicate that short-term creatine supplementation (20 to 25 g/d for 5 to 7-d) increases total body mass by approximately a 0.7 to 1.6 kg (see Table 3).^{5,6,8,40,43,72,75,78,89,109,115,116,123} In addition, a number of long-term (7 to 140-d) studies investigating the effects of creatine or creatine containing supplements (20 to 25 g/d for 5 to 7-d and 2 to 25 g/d thereafter) on body composition alterations during training have reported significantly greater gains in total body mass regimens ^{10,29,37,57,61,63,66,77,84,95,104,115} and fat-free mass.^{10,29,56,57,61,63,65,66,74,75,84,104,115} The gains in total body mass and fat-free mass (FFM) observed were typically 0.8 to 3 kg greater than matched-paired controls depending on the length and amount of supplementation. For example, Kreider et al.⁶⁴ reported that 28-d of creatine supplementation (15.75 g/d) resulted in a 1.1 kg greater gain in FFM in college football players undergoing off-season resistance/agility training. In addition, Vandenburghe and coworkers¹¹⁵ reported that untrained females ingesting creatine (20 g/d for 4-d followed by 5 g/d for 66-d) during resistance-training observed significantly greater gains in FFM (1.0 kg) than subjects ingesting a placebo during training. Moreover, the gains in FFM observed were maintained while ingesting creatine (5 g/d) during a 10-week period of detraining as well as following 4-weeks cessation of supplementation. Finally, preliminary data presented at the 1998 National Strength and Conditioning annual meeting from Dr. Bill Kraemer’s laboratory at Penn State University indicated that creatine supplementation (25 g/d for 7-d followed by 5 g/d for 77-d) promoted significant increases in muscle mass which was accompanied by an approximately 30% increase in type I and type II muscle fiber diameter. Collectively, these findings provide convincing evidence that creatine supplementation during training promotes muscle hypertrophy.

Although the majority of studies report that creatine supplementation increases body mass and/or lean body mass, the mechanism in which creatine supplementation may affect gains in body mass and/or fat free mass is not entirely clear. Nevertheless, there are three prevailing theories. First, since gains in body mass (about 1 kg) can occur within 3 to 7-d, some suggest that the gains in body mass observed are simply due to greater water retention. In support of this contention, initial studies reported that urine output declined during the first three days of creatine supplementation suggesting greater fluid retention.⁵⁰ Additionally, recent papers suggests that intracellular fluid volume increases during the first 3-d of creatine supplementation.^56,123,124 Yet, other studies which have evaluated the effects of long-term creatine supplementation on total body water have reported that the increases in total body water are proportional to the gains in weight (i.e., the percentage of total body water is not significantly changed).^63,64,66,108 In this regard, since muscle is approximately 70% water, an increase of 3 kg of muscle should be accompanied by 2.1 kg increase in body water. Consequently, although total body water may increases, it does not increase the percentage of total body water. Further, although initial gains in body mass can be explained to some degree by increases in total body water, the magnitude of change in muscle mass which has been reported in response to chronic creatine supplementation during training (mean changes as great as 5.5 kg in 6-weeks) argues against this theory. This is especially true when one considers that the gains in mass are typically accompanied by greater gains in strength, power, and/or sprint speed.

Second, creatine supplementation has been reported to affect protein synthesis.^{7,11,51,112,124} This theory suggests that an initial creatine stimulated gain in intracellular water may serve to increase osmotic pressure which in turn stimulates protein synthesis. There is some preliminary evidence to support this hypothesis.^11,83,123 For example, Ziegunfuss et al.¹²³ reported that nitrogen status was increased in a subset of subjects following 3-d of creatine supplementation suggesting that creatine increases protein synthesis and/or may decrease net protein breakdown. Kreider et al.⁶⁴ reported that the ration of urea nitrogen to creatinine (a general marker of anabolic/catabolic status) was decreased in athletes ingesting creatine (15.75 g/d for 28-d). Although additional research is necessary, these findings suggest that creatine supplementation may affect protein synthesis and/or reduce whole body catabolism during training.

Finally, some suggest that since creatine may allow an athlete to train harder, the enhanced training stimulus may promote greater muscle hypertrophy over time. Although this theory makes a lot of sense and can explain the increases in muscle mass reported in long-term studies, it should be noted that significant increases in muscle mass have been observed in as little as one week following creatine supplementation. Consequently, it is my view that the gains in muscle mass observed are most likely due to a combination of these theories.

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Is Creatine Safe?

Although there is strong evidence that creatine supplementation can improve exercise performance and lead to greater gains in muscle mass, concerns have been recently raised about potential side effects and/or the long-term safety of taking creatine. I am sure you have seen the headlines, read the newspapers, or heard reporters on television warn you about the side effects of creatine. Things like creatine causes cramping, muscle strains/pulls, upsets your stomach, causes diarrhea, and/or that we don’t know the long-term side effects of creatine. There have even been inaccurate reports that creatine was linked to deaths of some wrestlers and that the FDA was going to ban creatine. They’re logic has been that since creatine works, there have to be some side effects. Further, that we shouldn’t be recommending that athletes take this stuff. After all, many athletes used to take steroids and then we found out how dangerous they could be. Right?

I have been somewhat amazed at all of the hyperbole and misinformation regarding creatine supplementation that has appeared in the popular media over the last number of months. Interestingly, the scientific community is rather unified in its position about creatine supplementation (i.e., it works under certain exercise conditions and that more studies are needed to understand how it works and to continue to evaluate the medical uses/safety of creatine supplementation). Most of the negative comments I have seen about creatine have appeared in newspaper/magazine articles and/or on television. Often, they emanate from so called "experts" who are apparently not highly knowledgeable about the creatine literature, have never conducted any research on creatine (or in some cases no research at all), and/or have an apparent agenda against nutritional supplementation in general.

It is my view that we must be honest with athletes. Although most supplements sold to athletes have little to no research supporting their value, there are some supplements which studies show are effective under certain conditions (e.g., carbohydrate, creatine, sodium bicarbonate, sodium phosphate, protein/amino acids, glycerol etc.). In the case of creatine, it has been one of the most extensively studied nutritional supplements sold to athletes. There is little doubt that it works under certain conditions and all available evidence indicates that creatine supplementation is safe when taken at the recommended dosages. Nevertheless, a number of coaches, trainers, dietitians, and physiologists warn against its use. I am even aware of universities and high schools "banning" its administration and/or discussion in weight rooms. While I understand that its easier to tell athletes that supplements don’t work, that they may potentially be dangerous, and/or that supplements are a waste of money, in the case of creatine, this view is inconsistent with the available scientific literature. It is my view that comments about creatine should be based on the scientific literature, not speculation, untested hypotheses, or unsubstantiated fear. Those considering using creatine supplements should understand what it does and doesn’t do so that they can weigh the potential benefits against risks (if any). The following discusses the clinical effects of creatine on the body and the validity of anecdotally reported side effects.

Clinical Effects of Creatine Supplementation

When someone takes a 5 g dose of creatine, serum creatine levels typically increase for several hours.^7,47,72 This is why during the loading phase creatine should be ingested every 4 to 6 hours (4 to 5 times per day). Creatine storage into the muscle primarily occurs during the first several days of creatine supplementation.^47,91 Thereafter, excess creatine that is ingested is primarily excreted as creatine in the urine with small amounts converted to creatinine and urea.^7,17,47,91 Serum creatinine levels have been reported to be either not affected ^2,25 or slightly increased ^64,95 following 28-d, ⁶⁴ 56-d ^2,25 and 365-d ⁹⁵ of creatine supplementation. The increased serum and urinary creatinine have been suggested to reflect an increased release and cycling of intramuscular creatine as a consequence of enhanced muscle protein turnover in response to creatine supplementation and not of pathologic origin.^7,25,47,59 Yet, these increases have been a source of concern by some physicians in case reports of an athlete⁶⁸ or a patient with renal disease⁸⁸ taking creatine. The reason for this is that large elevations in serum and urinary creatinine levels are basic markers of tissue degradation and/or kidney stress. However, these reports have been criticized because intense exercise and dehydration increases serum and urinary creatinine levels.⁴¹ Consequently, in people who exercise, these increases reflect a greater breakdown of muscle protein and are completely normal. It makes sense then that if creatine supplementation allows an athlete to train harder, creatinine levels may be slightly elevated as the athlete may experience greater net protein degradation. Some studies which have administered creatine to athletes during training have reported slight increases in serum creatinine (e.g. 1.2 to 1.4 µmol/L).⁶⁴ Interestingly though, several studies which involved creatine supplementation without training have found no effects on serum or urinary creatinine levels.⁷⁵ These findings provide some indirect evidence that the elevations in creatinine are related to a greater ability to train harder rather than of pathological origin.

Along these same lines, several studies have evaluated the effects of creatine supplementation on muscle and liver enzyme levels. Muscle and liver enzymes increase in response to exercise training. These enzymes may also be elevated in response to degenerative muscle and/or liver disease. Studies show that creatine supplementation either has no effect ^2,95 or may moderately increase creatine kinase (CK), ^2,64 lactate dehydrogenase (LDH),⁶⁴ and/or aspartate amino transferase (AST)⁶⁴ levels following 28-d and 56-d of supplementation. The increased CK, LDH and AST levels reported following creatine supplementation were within normal limits for athletes engaged in heavy training and may reflect a greater concentration/activity of CK and/or ability to maintain greater training volume.^7,59,60,121 Interestingly, in studies in which creatine was administered in subjects not undergoing intense training, creatine supplementation does not appear to affect serum muscle enzyme efflux.^2,69,70,75

Creatine supplementation has also been reported to positively affect lipid profiles in middle-aged male and female hypertriglyceremic patients ²⁵ and trained male athletes.⁶⁴ In this regard, Earnest and colleagues ²⁵ reported that 56-d of creatine supplementation resulted in significant decreases in total cholesterol (-5 and -6% at day 28 and 56, respectively) and triglycerides (-23 and -22% at day 28 and 56, respectively) in mildly hypertriglyceremic patients. A similar response was observed with very low density lipoproteins (VLDL). In addition, Kreider and coworkers ⁶⁴ reported that 28-d of creatine supplementation increased high density lipoproteins (HDL) by 13%, while decreasing VLDL (-13%) and the ratio of total cholesterol to HDL (-7%). Although additional research is necessary, these findings suggest that creatine supplementation may posses health benefit by improving blood lipid profiles.

An extensive amount of research has been conducted on the potential medical benefits of intravenous PCr administration and oral creatine supplementation. In this regard, intravenous PCr administration has been reported to improve myocardial metabolism and reduced the incidence of ventricular fibrillation in ischemic heart patients.^{3,19,20,83,93,118,119} The reason for this is that PCr appears to enhance the viability of the ischemic cell membrane thereby minimizing injury cell during ischemia. Consequently, there has been interest in determining the effects of oral creatine supplementation on heart function and exercise capacity in patients with heart disease. Gordon and associates ³⁸ reported that creatine supplementation (20 g/d for 10-d) did not improve ejection fraction in heart failure patients with an ejection fraction less than 40%. However, creatine supplementation significantly increased one legged knee extension exercise performance (21%), peak torque (5%) and cycle ergometry performance (10%).

Creatine supplementation has also been used to treat patients with mitochondrial cytopathies (a condition which reduces exercise capacity) and infants with in-born errors in creatine synthesis. For example, Tarnapolosky et al.¹⁰⁷ reported that creatine supplementation (5 g/d for 14-d followed by 2 g/d for 7-d) significantly increased anaerobic and high-intensity aerobic exercise capacity in patients with mitochondrial cytopathy. Moreover, several case reports have been published in the medical literature which indicate that creatine supplementation (4 to 8 g/d for up to 25 months) allows infants with inborn errors in creatine synthesis to develop more mentally and physically normal.^4,34,99-103 Collectively, these findings suggest that intravenous PCr administration and/or oral creatine supplementation for up to 25 months in duration is safe and may posses some therapeutic value to certain patient populations.

What’s the bottom line? If you take creatine your serum and urinary creatine levels will increase for several hours after supplementation. Without training, there appears to be little if any impact on serum and urinary creatinine, muscle and liver enzymes, or blood pressure.^75,84 However, if you take creatine during training you may observe an increase in serum creatinine, CK, LDH and possibly AST. These elevations appear to be related to excess creatine being excreted and/or due to a greater ability to train harder following creatine supplementation. You may also experience some positive effects on your blood lipid profiles. Although additional research is necessary to evaluate the long-term effects of creatine supplementation on medical status, available studies suggest that creatine supplementation for up to 2 years is medically safe and may provide health benefit for various populations when taken at dosages described in the literature.

Side Effects

The only side effect reported from clinical studies investigating dosages of 1.5 to 25 g/d for 3- to 365-days in preoperative and post-operative patients, untrained subjects, and elite athletes has been weight gain.^7,59,60,121 However, a number of concerns about possible side effects of creatine supplementation have been mentioned in lay publications, supplement advertisements, and on Internet mailing lists. It should be noted that these concerns emanate from unsubstantiated anecdotal reports and may be unrelated to creatine supplementation. There is no evidence from any well-controlled clinical study indicating that creatine supplementation causes any of these side effects. However, one must also consider that although researchers are required to report side effects in scientific publications, few long-term studies on creatine supplementation have been conducted. Consequently, discussion about possible side effects is warranted.

Some concern has been raised whether creatine supplementation may suppress endogenous creatine synthesis. Studies have reported that it takes about four weeks after cessation of creatine supplementation for muscle creatine ³² and phosphocreatine ¹¹⁵ levels to return to normal. While it is unclear whether muscle creatine or phosphocreatine content falls below normal thereafter, there is no evidence that creatine supplementation causes a long-term suppression of creatine synthesis.^7,50

Since creatine is an amino acid, it has been suggested that creatine supplementation may increase renal stress or cause liver damage. However, no studies have reported clinically significant elevations in liver enzymes in response to creatine supplementation.^2,64 Further, Poortmans and colleagues ⁸⁶ reported that short-term creatine supplementation (20 g/d for 5-d) does not affect markers of renal stress. Moreover, preliminary results reported at the 1998 American College of Sports Medicine annual meeting from this group indicate that longer term creatine supplementation (9 weeks) does not affect markers of renal stress. Consequently, there is no evidence that creatine supplementation increases renal stress when taken at recommended dosages.

There have also been some anecdotal claims that athletes training hard in hot or humid conditions may experience a greater incidence of severe muscle cramps and/or muscle injury when taking creatine. However, no study has reported that creatine supplementation causes cramping, dehydration, changes in electrolyte concentrations, or increases susceptibility to muscle strains/pulls even though some of these studies have evaluated highly trained athletes undergoing intense training ^{14,36,45,48,57,61,63-66,73,78,91,104,110,116} in hot/humid environments. ^{36,61,63,65,104} For example, data that we recently presented at the 1998 National Strength and Conditioning Association indicated no reports of muscle cramping or injury in athletes involved in our previous creatine studies.⁶⁷ Most creatine researchers feel that these observations are overblown.

Finally, concern has been expressed regarding unknown long-term side effects. While long-term (> 1 year) well-controlled clinical trials have yet to be performed, it should be noted that athletes have been using creatine as a nutritional supplement since the mid 1960s. Yet, this author is not aware of any significant medical complications that have been directly linked to creatine supplementation. Additionally, preliminary data presented at the 1998 American College of Sports Medicine Annual Meeting from Dr. Mike Stone’s laboratory indicate that long-term creatine supplementation (up to 2 years) does not result in any abnormal clinical outcome in comparison to controls. Consequently, from the literature currently available, creatine supplementation appears to be medically safe when taken at dosages described in the literature.

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Summary and Conclusions

Based on available research, short-term creatine supplementation may improve maximal strength/power by 5 to 15%, work performed during sets of maximal effort muscle contractions by 5 to 15%, single-effort sprint performance by 1 to 5%, and work performed during repetitive sprint performance by 5 to 15%. Moreover, long-term supplementation of creatine or creatine containing supplements (15 to 25 g/d for 5 to 7-d and 2 to 25 g/d thereafter for 7 to 140-d) may promote significantly greater gains in strength, sprint performance, and fat free mass during training in comparison to matched-paired controls. However, not all studies have reported ergogenic benefit possibly due to differences in subject response to creatine supplementation, length of supplementation, exercise criterion evaluated, and/or the amount of recovery observed during repeated bouts of exercise. The only side effect from creatine supplementation reported in the scientific literature from studies lasting up to two years in non-athletes, athletes, and patient populations has been weight gain. Consequently, creatine supplementation appears to be a safe and effective nutritional strategy to enhance exercise performance and promote muscle hypertrophy.

Please send us your feedback on this article.

Richard B. Kreider, PhD, FACSM
rkreider@memphis.edu 

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