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.
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.7,17,49,59,60,77,121Most 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.7,17,49,60,121The 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).7,17,49This 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
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.59,60,121Loading 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.17Although 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, 91,92,115For example, Harris and coworkers47reported 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 associates8reported 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.50Studies show that the greatest amount of creatine uptake occurs during the first 3- to 5-d of ingesting loading doses.47,50The elevated levels of muscle TCr and PCr can be maintained thereafter by ingesting 2 to 5 g/d.50,115Following 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.43,47In 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 studies39,40indicate 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.
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.8,15,16,32,42,43,72,115These studies indicate that creatine supplementation does not appear to alter pre-exercise ATP concentrations.32,47However, the elevated PCr concentrations serve to maintain ATP concentrations to a greater degree during maximal effort high intensity exercise.16In addition, creatine supplementation appears to enhance the rate of ATP and PCr resynthesis following intense exercise.8,15,16,32,42,43,72,115Since 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.
|Table 1. Summary of the types of exercise and/or exercise conditions in which creatine supplementation has been reported to provide ergogenic benefit.|
|One Repetition Maximum and/or Peak Power10,12,24,28,29,38,44,54,56,57,65,74,76,82,89,94,115,116,117,119,120,124|
|Vertical Jump 13,37,104|
|Work Performed During Multiple Sets of Maximal Effort Muscle Contractions 1,3,13,29,38,44,46,54,64,69,72,98,115,116,117|
|Single Sprints/Maximal Effort Contractions Lasting 6 to 30-s1,8,12,16,28,29,33,44,45,70,87,94,104,124|
|Repetitive Sprints (recovery 0.5 to 5-min)1,5,8,12,24,27,29,31,33,48,55,57,64,73,74,85,91,109,124|
|High Intensity Exercise Lasting 1.5 to 10-min 26,27,30,48,97|
|Increased Ventilatory Anaerobic Threshold 80|
|Increase Maximal Exercise Capacity 52|
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.10,12,24,28,29,38,44,54,56,57,65,74,76,89,94,115,116,117,120,124For example, Earnest and associates29reported 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 colleagues116reported 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.12,24,38,44,54,57,124For example, Dawson and coworkers24reported 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 colleagues12reported 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 power54as well as vertical jump performance.13,37,104These 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.
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.1,3,13,29,38,44,46,54,64,69,72,98,115,116,117,122For example, Bosco et al13found 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 colleagues116reported 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 associates29found 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.64reported 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.
Creatine supplementation has also been reported to improve single effort1,8,12,16,28,29,33,44,45,70,87,94,104,123and/or repetitive sprint performance1,5,8,12,24,27,29,31,33,48,55,57,64,71,73,74,85,91,109,121,123particularly in sprints lasting 6 to 30-s with 30-s to 5-min of rest recovery between sprints. For example, Birch et al12reported 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 coworkers45reported 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 associates64reported 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 colleagues29reported 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.14,26,27,30,32,48,97,108The 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 coworkers48reported 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 colleagues26,27and Smith et al.97found that creatine supplementation significantly increased high intensity exercise performance lasting up to 600-s in duration. Moreover, Rossiter et al.91reported 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 associates52reported 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.
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.6,31,36,79These studies indicate that short-term creatine supplementation does not appear to improve submaximal exercise performance. In fact, Balsom and colleagues6reported 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.
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.43,47It 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-d9,53,92,81or involve low-dose supplementation regimens (2 to 3 g/d) without an initial higher dose loading period.44,52In 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.32,72,81,92Creatine 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.14,22,78,90Finally, short-term creatine supplementationdoes not appear to enhance endurance exercise.31,36,79Consequently, although most studies indicate that creatine supplementation may improve performance, creatine supplementation may not provide ergogenic value for everyone.
|Table 2. Summary of types of exercise and/or exercise conditions in which creatine supplementation has been reported to provide no ergogenic benefit.|
|One Repetition Maximum or Peak Force4,46,98,106,119,122|
|Vertical Jump 76|
|Work Performed During Multiple Sets of Low Intensity or Maximal Effort Muscle Contractions35,69,82,89,110,106|
|Single Sprints Lasting 6 to 30-s 13,24,37,53,81,85,92|
|Repetitive Sprints (recovery 30- to 120-s 51 and 5- to 25-min)9,14,21,22,78,90,94,96,111,114|
|Exercise Lasting 60-220-s14,32,108|
|Submaximal Endurance Exercise 31,36,79,105|
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).5,6,8,40,43,72,75,78,89,109,115,116,123In 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 10,29,37,57,61,63,66,77,84,95,104,115and fat-free mass.10,29,56,57,61,63,65,66,74,75,84,104,115The 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.64reported 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 coworkers115reported 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.
|Table 3. Effects of Creatine on Body Mass and Composition|
|Significant Increase in Total Body Mass Following Short-term Supplementation Regimens 5,6,8,40,43,72,75,78,89,109,115,116,122|
|No Significant Effect on Total Body Mass or Fat Free Mass Following Short-term Supplementation Regimens25,36,45,46,76,90,108,116|
|Significant Increase in Total Body Mass Following Long-term Supplementation Regimens 10,29,37,57,61,63,66,77,84,95,104,116|
|Significant Increase in Fat Free Mass following Short- and/or Long-term Creatine Supplementation10,29,56,57,61,63,65,66,74,75,77,84,104,116,121,124|
|No Significant Changes in Fat Free Mass following Short- and/or Long-term Creatine Supplementation 122|
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.50Additionally, recent papers suggests that intracellular fluid volume increases during the first 3-d of creatine supplementation.56,123,124Yet, 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).63,64,66,108In 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.7,11,51,112,124This 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.11,83,123For example, Ziegunfuss et al.123reported 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.64reported 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.
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.
When someone takes a 5 g dose of creatine, serum creatine levels typically increase for several hours.7,47,72This 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.47,91Thereafter, excess creatine that is ingested is primarily excreted as creatine in the urine with small amounts converted to creatinine and urea.7,17,47,91Serum creatinine levels have been reported to be either not affected2,25or slightly increased64,95following 28-d,6456-d2,25and 365-d95of 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.7,25,47,59Yet, these increases have been a source of concern by some physicians in case reports of an athlete68or a patient with renal disease88taking 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.41Consequently, 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).64Interestingly though, several studies which involved creatine supplementation without training have found no effects on serum or urinary creatinine levels.75These 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 effect2,95or may moderately increase creatine kinase (CK),2,64lactate dehydrogenase (LDH),64and/or aspartate amino transferase (AST)64levels 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.7,59,60,121Interestingly, 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 topositivelyaffect lipid profiles in middle-aged male and female hypertriglyceremic patients25and trained male athletes.64In this regard, Earnest and colleagues25reported 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 coworkers64reported 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 healthbenefitby 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.3,19,20,83,93,118,119The 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 associates38reported 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.107reported 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.4,34,99-103Collectively, 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.75,84However, 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.
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 beenweight gain.7,59,60,121However, 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 isnoevidence 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 aboutpossibleside 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 creatine32and phosphocreatine115levels 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.2,64Further, Poortmans and colleagues86reported 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 someof these studies have evaluated highly trained athletes undergoing intense training14,36,45,48,57,61,63-66,73,78,91,104,110,116in hot/humid environments.36,61,63,65,104For 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.67Most 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.
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.
1. Almada A, Kreider R, Ferreira M, Wilson M, Grindstaff P, Plisk S, Reinhardy J, Cantler E.Effects of calcium ß-HMB supplementation with or without creatine during training on strength and sprint capacity. FASEB J 1997;11:A374. Abstract
2. Almada A, Mitchell T, Earnest C. Impact of chronic creatine supplementation on serum enzyme concentrations. FASEB J 1996;10:A4567. Abstract
3. Andrews R, Greenhaff P, Curtis S, Perry A, Cowley AJ. The effect of creatine supplementation on skeletal muscle metabolism in congestive heart failure. Eur Heart J. 1998;19:617-622.
4. Arias-Mendoza F, Konchanin LM, Grover WD, Salganicoff L, Selak MA, Brown TR. Possible creatine synthesis deficit studied by in vivo magnetic resonance spectroscopy. Med Sci Sports Exerc. 1998;30:S234. Abstract.
5. Balsom P, Ekblom B, Sjodin B, Hultman E. Creatine supplementation and dynamic high-intensity intermittent exercise. Scand J Med Sci Sport 1993;3:143-9.
6. Balsom P, Harridge S, Söderlund K, Sjodin B, Ekblom B. Creatine supplementation per se does not enhance endurance exercise performance. Acta Physiol Scand 1993;149:521-3.
7. Balsom P, Söderlund K, Ekblom B. Creatine in humans with special references to creatine supplementation. Sports Med 1994;18:268-80.
8. Balsom P, Söderlund K, Sjödin B, Ekblom B. Skeletal muscle metabolism during short duration high-intensity exercise: influence of creatine supplementation. Acta Physiol Scand 1995;1154:303-10.
9. Barnett C, Hinds M, Jenkins D. Effects of oral creatine supplementation on multiple sprint cycle performance. Aust J Sci Med. Sport 1996;28:35-9.
10. Becque B, Lochmann J, Melrose D. Effect of creatine supplementation during strength training on 1 RM and body composition. Med Sci Sport Exerc 1997;29:S146.Abstract
11. Bessman S, Savabi F. The role of the phosphocreatine energy shuttle in exercise and muscle hypertrophy. In: Taylor A, Gollnick P, Green H editors. International Series on Sport Sciences: Biochemistry of Exercise VII: Champaign, IL: Human Kinetics, 1988:167-78.
12. Birch R, Noble D, Greenhaff P. The influence of dietary creatine supplementation on performance during repeated bouts of maximal isokinetic cycling in man. Eur J Appl Physiol 1994;69:268-70.
13. Bosco C, Tihanyi J, Pucspk J, Kovacs I, Gobossy A, Colli R, Pulvirenti G, Tranquilli C, Foti C, Viru M, Viru A. Effect of oral creatine supplementation on jumping and running performance. Int J Sports Med 1997;18:369-72.
14. Burke L, Pyne D, Telford R. Effect of Oral creatine supplementation on single-effort sprint performance in elite swimmers. Int J Sport Nutr. 1996;6:222-33.
15. Brannon,T. Effects of creatine loading and training on running performance and biochemical properties of rat muscle. Med Sci Sport Exerc 1997;29:489-95.
16. Casey A, Constantin-Teodosiu D, Howell D, Hultman E, Greenhaff P. Creatine ingestion favorably affects performance and muscle metabolism during maximal exercise in humans. Am J Physiol 1996;271:E31-7. Abstract
17. Chanutin A. The fate of creatine when administered to man. J Biol Chem 1926;67:29-41.
18. Chetlin R, Schoenleber J, Bryner R, Gordon P, Ullrich I, Yeater R. The effects of two forms of oral creatine supplementation on anaerobic performance during the Wingate test. J Str Cond Res. 1998;12:In press. Abstract
19. Constantin-Teodosiu D, Greenhaff P, Gardiner S, Randall M, March J, Bennett T. Attenuation by creatine of myocardial metabolic stress in Brattleboro rats caused by chronic inhibition of nitric oxide synthase. Br J Pharmacol 1995;116:3288-92.
20. Conway M, Clark J editors. Creatine and Creatine Phosphate: Scientific and Clinical Perspectives. San Diego, CA: Academic Press, 1996.
21. Cooke W., Barnes W. The influence of recovery duration on high-intensity exercise performance after oral creatine supplementation. Can J Appl Physiol 1997;22:454-67.
22. Cooke W, Grandjean P, Barnes W. Effect of oral creatine supplementation on power output and fatigue during bicycle ergometry. J Appl Physiol 1995;78:670-3.
23. Cordain L. Does creatine supplementation enhance athletic performance? J Am Coll Nutr 1998;17:205-206.
24. Dawson B, Cutler M, Moody A, Lawrence S, Goodman C, Randall N. Effects of oral creatine loading on single and repeated maximal short sprints. Aust J Sci Med Sport 1995;27:56-61.
25. Earnest C, Almada A, Mitchell T. High-performance capillary electrophoresis-pure creatine monohydrate reduces blood lipids in men and women. Clin Sci 1996;91:113-18.
26. Earnest C, Almada A, Mitchell T. Effects of creatine monohydrate ingestion on intermediate duration anaerobic treadmill running to exhaustion. J Str Cond Res 1997;11:234-8.
27. Earnest C, Beckham S, Whyte BO, Almada AL. Effect of acute creatine ingestion on anaerobic performance. Med Sci Sports Exerc. 1998;30:S141. Abstract.
28. Earnest C, Beckham S, Whyte BO, Almada AL. Acute creatine monohydrate ingestion and anaerobic performance in men and women. J Str Cond Res. 1998; 12:In press. Abstract
29. Earnest C, Snell P, Rodriguez R, Almada A, Mitchell T. The effect of creatine monohydrate ingestion on anaerobic power indices, muscular strength and body composition. Acta Physiol Scand 1995;153:207-9.
30. Earnest C, Stephens D, Smith J. Creatine ingestion effects time to exhaustion during estimation of the work rate-time relationship. Med Sci Sport Exerc 1997;29:S285. Abstract
31. Englehardt, M., Neumann G., Berbalk, A., Reuter, I. Creatine supplementation in endurance sports. Med Sci Sports Exerc 1998;30:1123-1129.
32. Febbraio M, Flanagan T, Snow R, Zhao S, Carey M. Effect of creatine supplementation on intramuscular TCr, metabolism and performance during intermittent, supramaximal exercise in humans. Acta Physiol Scand 1995;155:387-95.
33. Ferreira M, Kreider R, Wilson M, Grindstaff P, Plisk S, Reinhardy J, Cantler E, Almada A. Effects of ingesting a supplement designed to enhance creatine uptake on strength and sprint capacity. Med Sci Sport Exerc 1997;29:S146. Abstract
34. Ganesan V, Johnson A, Connelly A, Eckhardt S, Surtees RA. Guanidinoacetate methyltransferase deficiency: new clinical features. Pediatr Neurol 1997;17:155-157.
35. Gilliam JD, Hohzom C, Martin AD. Effect of oral creatine supplementation on isokinetic force production. Med Sci Sports Exerc. 1998;30:S140. Abstract.
36. Godly A, Yates J. Effects of creatine supplementation on endurance cycling combined with short, high-intensity bouts. Med Sci Sport Exerc 1997;29:S251. Abstract
37. Goldberg P, Bechtel P. Effects of low dose creatine supplementation on strength, speed and power by male athletes. Med Sci Sport Exerc 1997;29:S251. Abstract
38. Gordon A, Hultman E, Kaijser L, Kristgansson S, Rolf C, Nyquist O, Sylven C. Creatine supplementation in chronic heart failure increases skeletal muscle creatine phosphate and muscle performance. Cardiovasc Res 1995;30:413-18.
39. Green A, Sewell D, Simpson L, Hulman E, Macdonald I, Greenhaff P. Creatine ingestion augments muscle creatine uptake and glycogen synthesis during carbohydrate feeding in man. J Physiol 1996;491:63. Abstract
40. Green A, Simpson E, Littlewood J, Macdonald I, Greenhaff P. Carbohydrate ingestion augments creatine retention during creatine feedings in humans. Acta Physiol Scand 1996;158:195-202.
41. Greenhaff P. Renal dysfunction accompanying oral creatine supplements. Lancet. 1998; 352:233-234.
42. Greenhaff P, Bodin K, Harris R, Hultman E, Jones D, McIntyre D, Soderlund K, Turner, DL. The influence of oral creatine supplementation on muscle phosphocreatine resynthesis following intense contraction in man. J Physiol 1993;467:75P. Abstract
43. Greenhaff P, Bodin K, Söderlund K, Hultman E. Effect of oral creatine supplementation on skeletal muscle phosphocreatine resynthesis. Am J Physiol. 1994;266:E725-30.
44. Greenhaff P, Casey A, Short A, Harris R, Söderlund K, Hultman E. Influence of oral creatine supplementation of muscle torque during repeated bouts of maximal voluntary exercise in man. Clin Sci 1993;84:565-71.
45. Grindstaff P, Kreider R, Bishop R, Wilson M, Wood L, Alexander C, Almada A.Effects of creatine supplementation on repetitive sprint performance and body composition in competitive swimmers. Int J Sport Nutr 1997;7:330-46.
46. Hamilton-Ward K, Meyers M, Skelly W, Marley R, Saunders J. Effect of creatine supplementation on upper extremity anaerobic response in females. Med Sci Sport Exerc 1997;29:S146. Abstract
47. Harris R, Söderlund K, Hultman E. Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clin Sci 1992;83:367-74.
48. Harris R, Viru M, Greenhaff P, Hultman E. The effect of oral creatine supplementation on running performance during maximal short term exercise in man. J Physiol 1993;467:74P. Abstract
49. Hultman E, Bergstrom J, Spriet L, Söderlund K. Energy metabolism and fatigue. In: Taylor A, Gollnick P, Green H, editors. Biochemistry of Exercise VII. Champaign, IL: Human Kinetics, 1990:73-92.
50. Hultman E, Söderlund K, Timmons J, Cederblad G, Greenhaff P. Muscle creatine loading in man. J Appl Physiol 1996;81:232-7.
51. Ingwall J. Creatine and the control of muscle-specific protein synthesis in cardiac and skeletal muscle. Circ Res 1976;38:I115-23.
52. Jacobs I, Bleue S, Goodman J. Creatine ingestion increases anaerobic capacity and maximum accumulated oxygen deficit. Can J Appl Physiol 1997;22:231-43.
53. Javeirre C, Lizarraga MA, Ventura JL, Garrido E, Segura R. Creatine supplementation does not improve physical performance in a 150 m race. Rev Esp Fisiol. 1997;53:343-348.
54. Johnson K, Smodic B, Hill R. The effects of creatine monohydrate supplementation on muscular power and work. Med Sci Sport Exerc 1997;29:S251. Abstract
55. Jones AM, Atter T, George KP. Oral creatine supplementation improves multiple sprint performance in elite ice-hockey players. Med Sci Sports Exerc. 1998;30:S140. Abstract.
56. Knehans A, Bemben M, Bemben D, Loftiss D. Creatine supplementation affects body composition and neuromuscular performance in football athletes. FASEB J. 1998;A863. Abstract
57. Kirksey K, Warren B, Stone M, Stone M, Johnson R. The effects of six weeks of creatine monohydrate supplementation in male and female track athletes. Med Sci Sport Exerc 1997;29:S145. Abstract
58. Kreider R. Effects of creatine loading on muscular strength and body composition. Str Cond 17:72-3, 1995.
59. Kreider, R.B. Creatine, the next ergogenic supplement? In Sportscience Training & Technology, Internet Society for Sport Science. Available: http://www.sportsci.org/traintech/creatine/rbk.html 1998.
60. Kreider, R. B. Creatine supplementation: Analysis of ergogenic value, medical safety, and concerns. Journal of Exercise PhysiologyOnline. 1(1): 7-19, 1998. Available: http://www.css.edu/users/tboone2/asep/jan3.htm
61. Kreider R, Ferreira M, Wilson M, Almada A. Effects of creatine supplementation with and without glucose on body composition in trained and untrained men and women. J. Str Cond Res. 1997;11:283. Abstract
62. Kreider R, Ferreira M, Wilson M, Grindstaff P, Plisk S, Reinhardy J, Cantler E, Almada A. Effects of ingesting a supplement designed to enhance creatine uptake on body composition during training. Med Sci Sport Exerc 1997;29:S145. Abstract
63. Kreider R, Ferreira M, Wilson M, Grindstaff P, Plisk S, Reinhardy J, Cantler E, Almada A. Effects of calcium ß-HMB supplementation with or without creatine during training on strength and sprint capacity. FASEB J 1997;11:A374. Abstract
64. Kreider R, Ferreira M, Wilson M, Grindstaff P, Plisk S, Reinhardy J, Cantler E, Almada A. Effects of creatine supplementation on body composition, strength and sprint performance. Med Sci Sport Exerc 1998;30:73-82.
65. Kreider R, Grindstaff P, Wood L, Bullen D, Klesges R, Lotz D, Davis M, Cantler E, Almada A..Effects of ingesting a lean mass promoting supplement during resistance training on isokinetic performance. Med Sci Sport Exerc 1996;28:S36. Abstract
66. Kreider R, Klesges R, Harmon K, Grindstaff P, Ramsey L, Bullen D, Wood L, Li Y, Almada A. Effects of ingesting supplements designed to promote lean tissue accretion on body composition during resistance exercise. Int J Sport Nutr 1996;6:234-46.
67. Kreider R, Rasmussen C, Ransom J, Almada A. Effects of creatine supplementation during training on the incidence of muscle cramping, injuries, and GI distress. J Str Cond Res. 1998; 12:In press. Abstract
68. Kuehl K, Goldberg L, Elliot D. Renal insufficiency after creatine supplementation in a college football athlete. Med Sci Sports Exerc. 1998;30:S235. Abstract.
69. Kurosawa Y, Iwane H, Hamaoka T, Shimomitsu T, Katsumura T, Sako T, Kuwamon M, Kimura N. Effects of oral creatine supplementation on high-and low-intensity grip exercise performance. Med Sci Sport Exerc 1997;29:S251. Abstract
70. Kurosawa Y, Katsumura T, Hamoaka T, Sako T, Kuwamori M, Kimura N, Shimomitsu T. Effects of oral creatine supplementation on localized muscle performance and muscle creatine phosphate concentration. Jap J Phys Fit Sports Med. 1998;47:361-366.
71. Lefavi RG, McMillan JL, Kahn PJ, Crosby JF, Digioacchino RF, Streater JA. Effects of creatine monohydrate on performance of collegiate baseball and basketball players. J Str Cond Res. 1998; 12:In press. Abstract
72. Lemon P, Boska M, Bredle D, Rogers M, Ziegenfuss T, Newcomer B. Effect of oral creatine supplementation on energetic during repeated maximal muscle contraction. Med Sci Sport Exerc 1995;27:S204. Abstract
73. Leenders N, Lesniewski L, Sherman W, Sand G, Sand S, Mulroy M, Lamb D. Dietary creatine supplementation and swimming performance. Overtraining and Overreaching in Sport Conference Abstracts. 1996;1:80. Abstract
74. Michaelis J, Vukovich M. Effect of two different forms of creatine supplementation on muscular strength and power. Med Sci Sports Exerc. 1998;30:S272. Abstract.
75. Mihic S, MacDonald JR, McKenzie S, Tarnopolsky MA. The effect of creatine supplementation on blood pressure, plasma creatine kinase, and body composition. FASEB J. 1998;12:A652. Abstract
76. Miszko TA, Baer JT, Vanderburgh PM. The effect of creatine loading on body mass and vertical jump of female athletes. Med Sci Sports Exerc. 1998;30:S141. Abstract.
77. Mujika I, Padilla S. Creatine supplementation as an ergogenic aid for sports performance in highly trained athletes: a critical review. Int J Sports Med. 1997;18:491-496.
78. Mujika I, Chatard J, Lacoste L, Barale F, Geyssant A. Creatine supplementation does not improve sprint performance in competitive swimmers. Med Sci Sport Exerc 1996;28:1435-41.
79. Myburgh K, Bold A, Bellinger B, Wilson G, Noakes T. Creatine supplementation and sprint training in cyclists: metabolic and performance effects. Med. Sci. Sport Exerc. 1996;28:S81. Abstract
80. Nelson A, Day R, Glickman-Weiss E, Hegstad M, Sampson B. Creatine supplementation raises anaerobic threshold. FASEB J 1997;11:A589. Abstract
81. Odland L, MacDougall J, Tarnopolsky M, Elorriage A, Borgmann A. Effect of oral creatine supplementation on muscle [PCr] and short-term maximum power output. Med Sci Sport Exerc 1997;29:216-219.
82. Oopik V, Paasuke M, Timpamann S, Medijainen L, Ereline J, Smirnova T. Effect of creatine supplementation during rapid body mass reduction on metabolism and isokinetic muscle performance capacity. Eur J Appl Physiol 1998;78:83-92.
83. Pauletto P, Strumia E. Clinical experience with creatine phosphate therapy. In Conway M and Clark J. editors. Creatine and Creatine Phosphate: Scientific and Clinical Perspectives. San Diego, CA: Academic Press, 1996:185-98.
84. Peeters BM, Lantz CD, Mayhew JL. Effect of oral creatine monohydrate and creatine phosphate supplementation on maximal strength indices, body composition, and blood pressure. J Str Cond Res. 1998; 12:In press.
85. Peyrebrune MC, Nevill ME, Donaldson FJ, Cosford DJ. The effects of oral creatine supplementation on performance in a single and repeated sprint swimming. J Sports Sci. 1998; 16:271-279.
86. Poortmans J, Auquier H, Renaut V, Durassel A, Saugy M, Brisson G. Effect of short-term creatine supplementation on renal responses in men. Eur J Appl Physiol 1997;76:566-7.
87. Prevost M, Nelson A, Morris G. The effects of creatine supplementation on total work output and metabolism during high-intensity intermittent exercise. Res Q Exerc Sport 1997;68:233-40.
88. Pritchard NR, Kaira PA. Renal dysfunction accompanying oral creatine supplements. Lancet 1998 Apr 25;351(9111):1252-1253.
89. Rawson ES, Clarkson PM, Melanson EL. The effects of oral creatine supplementation on body mass, isometric strength, and isokinetic performance in older individuals. Med Sci Sports Exerc. 1998;30:S140. Abstract.
90. Redondo D, Dowling E, Graham B, Almada A, Williams M. The effect of oral creatine monohydrate supplementation on running velocity. Int J Sport Nutr 1996;6:213-21.
91. Rossiter H, Cannell E, Jakeman P. The effect of oral creatine supplementation on the 1000-m performance of competitive rowers. J Sports Sci 1996;14:175-9.
92. Ruden T, Parcell A, Ray M, Moss K, Semler J, Sharp R, Rolfs G, King D. Effects of oral creatine supplementation on performance and muscle metabolism during maximal exercise. Med Sci Sport Exerc 1996;28:S81. Abstract
93. Saks V, Stepanov V, Jaliashvili I, Konerev E, Kryzkanovsky S, Strumia E. Molecular and cellular mechanisms of action for cardioprotective and therapeutic role of creatine phosphate. In Conway M, Clark J editors. Creatine and Creatine Phosphate: Scientific and Clinical Perspectives. San Diego, CA: Academic Press, 1996:91-114.
94. Schneider D., McDonough P, Fadel P, Berwick J. Creatine supplementation and the total work performed during 15-s and 1-min bouts of maximal cycling. Aust J Sci Med Sport. 1997;29(3):65-8.
95. Sipila I, Rapola J, Simell O, Vannas A. Supplementary creatine as a treatment for gyrate atrophy of the choroid and retina. New Eng J Med 1981;304:867-70.
96. Smart NA, McKenzie SG, Nix LM, Baldwin SE, Page K, Wade D, Hampson PK. Creatine supplementation does not improve repeat sprint performance in soccer players. Med Sci Sports Exerc. 1998;30:S140. Abstract.
97. Smith JC, Stephens DP, Hall EL, Jackson AW, Earnest CP. Effect of oral creatine ingestion on parameters of the work rate-time relationship and time to exhaustion in high-intensity cycling. Eur J Appl Physiol. 1998;77:360-365.
98. Stevenson SW, Dudley GA. Creatine supplementation and resistance exercise. J Str Cond Res. 1998; 12:In press. Abstract
99. Stockler S, Hanefeld F. Guanidinoacetate methyltransferase deficiency: a newly recognized inborn error of creatine biosynthesis. Wien Klin Wochenschr 1997 Feb 14;109(3):86-88.
100. Stockler S, Hanefeld F, Frahm J. Creatine replacement therapy in guanidinoacetate methyltransferase deficiency, a novel inborn error of metabolism. Lancet. 1996; 21;348:789-790.
101. Stockler S, Holzbach U, Hanefeld F, Marquardt I, Helms G, Requart M, Hanicke W, Frahm J. Creatine deficiency in the brain: a new, treatable inborn error of metabolism. Pediatr Res. 1994; 36:409-413.
102. Stockler S, Isbrandt D, Hanefeld F, Schmidt B, von Figura K. Guanidinoacetate methyltransferase deficiency: the first inborn error of creatine metabolism in man. Am J Hum Genet. 1996;58:914-922.
103. Stockler S, Marescau B, De Deyn PP, Trijbels JM, Hanefeld F. Guanidino compounds in guanidinoacetate methyltransferase deficiency, a new inborn error of creatine synthesis. Metabolism. 1997;46:1189-1193.
104. Stout J, Eckerson J, Noonan D, Moore G, Cullen D. The effects of a supplement designed to augment creatine uptake on exercise performance and fat-free mass in football players. Med Sci Sport Exerc 1997;29:S251. Abstract
105. Stroud M, Holliman D, Bell D, Green A, MacDonald I, Greenhaff P. Effect of oral creatine supplementation on respiratory gas exchange and blood lactate accumulation during steady-state incremental treadmill exercise and recovery in man. Clin Sci 1994;87:707-10.
106. Syrotuik DG, Bell GJ, Burnham R, Sim LL, Calvert RA, MacLean IM. Absolute ane relative strength performance following creatine monohydrate supplementation combined with periodized resistance training. J Str Cond Res. 1998; 12:In press. Abstract
107. Tarnapolosky M, Roy B, MacDonald J. A randomized controlled trial of creatine monohydrate in patients with mitochondrial cytopathies. Muscle Nerve 1997;20:1502-9.
108. Terrilion K, Kolkhorst F, Dolgener F, Joslyn S. The effect of creatine supplementation on two 700-m maximal running bouts. Int J Sport Nutr 1997;7:138-43.
109. Theoduru A, Cooke CB, King RFGJ, Ducket R. The effect of combined carbohydrate and creatine ingestion on anaerobic performance. Med Sci Sports Exerc. 1998;30:S272. Abstract.
110 Thompson C, Kemp G, Sanderson A, Dixon R, Styles P, Taylor D, Radda G.Effect of creatine on aerobic and anaerobic metabolism in skeletal muscle in swimmers. Br J Sports Med 1996;30:222-5.
111. Thorensen E, McMillan J, Guion K, Joyner B. The effect of creatine supplementation on repeated sprint performance. J Str Cond Res. 1998; 12:In press. Abstract
112. Tullson P, Rundell K, Sabina R, Terjung R. Creatine analogue beta-guanidinopropionic acid alters skeletal muscle AMP deaminase activity. Am J Physiol 1996;270:C76-85.
113. Vanakoski J, Kosunen V, Meririnne E, Seppala T. Creatine and caffeine in anaerobic and aerobic exercise: effects on physical performance and pharmacokinetic considerations. Int J Clin Pharmacol Ther. 1998;36:258-262.
114. Vandenberghe K, Gillis N, Van Leemputte M, Van Hecke P, Vanstapel F, Hespel P. Caffeine counteracts the ergogenic action of muscle creatine loading. J Appl Physiol 1996;80:452-7.
115. Vanderberghe, K., Goris M., Van Hecke P., Van Leeputte M., Vangerven L., Hespel P. Long-term creatine intake is beneficial to muscle performance during resistance-training. J Appl Physiol 1997;83:2055-63.
116. Volek J, Kraemer W, Bush J, Boetes M, Incledon T, Clark K, Lynch J. Creatine supplementation enhances muscular performance during high-intensity resistance exercise. J Am Diet Assoc 1997;97:765-70.
117. Wakatsuki T, Ohira Y, Nakamura K, Asakura T, Ohno H, Yamamoto M. Changes of contractile properties of extensor digitorum longus in response to creatine-analogue administration and/or hindlimb suspension in rats. Jpn J Physiol 1995;45:979-89.
118. Wakatsuki T, Ohira Y, Yasui W, Nakamura K, Asakura T, Ohno H, Yamamoto M. Responses of contractile properties in rat soleus to high-energy phosphates and/or unloading. Jpn J Physiol 1994;44:193-204.
119. Walters PH, Olrich TW. The effects of creatine supplementation on strength performance. J Str Cond Res. 1998; 12:In press. Abstract
120. Warber JP, Patton JF, Tharion WJ, Montain SJ, Mello RP, Lieberman HR. Effects of creatine monohydrate supplementation on physical performance. FASEB J. 1998;12:A1040.Abstract
121. Williams MH, Branch JD. Creatine supplementation and exercise performance: an update. J Am Coll Nutr. 1998;17:216-234.
122. Wood KK, Zabik RM, Dawson ML, Frye PA. The effects of creatine monohydrate supplementation on strength, lean body mass, and circumferences in male weightlifters. Med Sci Sports Exerc. 1998;30:S272. Abstract.
123. Ziegenfuss T, Lemon P, Rogers M, Ross R, Yarasheski K. Acute creatine ingestion: effects on muscle volume, anaerobic power, fluid volumes, and protein turnover. Med Sci Sports Exerc 1997;29:S127. Abstract
124. Ziegunfuss T, Lemon PWR, Rogers M, Ross R, Yarasheski K. Acute Fluid Volume Changes in Men During Three Days of Creatine Supplementation. Journal of Exercise Physiology Online. 1998;1:In press.