Over the last decade, thousands of articles have been written about creatine supplementation in scientific journals, magazines, newspapers, and on the Internet. The reason for this interest is that creatine supplementation has proven to be one of the most effective methods available to increase strength, power, and muscle mass.1 Moreover, a number of potential therapeutic benefits of creatine supplementation have been suggested for various patient populations.2 Despite this impressive body of research, concerns have been raised about the safety of creatine supplementation and ethics of athletes taking performance-enhancing nutritional supplements.3,4 While a number of very good reviews have been published about creatine in the scientific literature1,2,5-8 a significant amount of misinformation has been written about creatine, particularly in the popular media. Additionally, several nutritional supplement companies have attempted to gain market share by perpetuating some of these creatine myths. The result is that people are often confused about the potential benefits and risks of creatine supplementation. The purpose of this article is to provide an update on the state of the science regarding creatine supplementation as well as to answer some common questions about creatine so that you can make an informed decision about whether to use creatine or not.

What is Creatine?
Creatine is a naturally occurring amino acid-like compound that is found primarily in the muscle (95%). There is also a small amount of creatine in the brain and testes. About two thirds of creatine found in the muscle is stored as phosphocreatine (PCr) while the remaining amount of creatine is stored as free creatine. The total creatine pool (PC + free creatine) in the muscle averages about 120 grams for a normal sized person. However, the body has the capacity to store up to 160 grams of creatine under certain conditions.

Sources of Creatine
The body breaks down 1 to 2% of the creatine pool per day (about 2 grams) into creatinine in the muscle. The creatinine is then excreted in urine. The body can replenish depleted creatine in two ways. First, about half of your daily creatine needs can be obtained from your normal diet by eating foods that contain creatine. For example, there is about 1 to 2 grams of creatine in a pound of uncooked beef and salmon. The remaining amount of creatine is synthesized from the amino acids glycine, arginine, and methionine. Normal dietary intake of creatine from food and creatine synthesis typically maintains creatine levels at about 120 grams for a normal size individual. Vegetarians have been reported to have lower than normal muscle creatine stores. Additionally, some people have been found to have creatine synthesis deficiencies and therefore must depend on dietary availability of creatine to maintain normal muscle concentrations.

Supplementation Protocols
The most common way to increase muscle creatine stores is to "load" creatine by taking 5 grams of creatine monohydrate four times per day for 5 to 7 days. Studies show that this protocol can increase muscle creatine and PC by 10 to 40%.2 Once muscle creatine stores are saturated, studies indicate that you only need to take 3 to 5 grams of creatine monohydrate per day in order to maintain elevated creatine stores. An alternative supplementation protocol is to ingest 3 grams/day of creatine monohydrate for 28-days 9. Studies show that this method can increase muscle concentrations of creatine as effectively as creatine loading techniques. However, this method would only result in a gradual increase in muscle creatine content compared to the more rapid loading method. Some athletes also cycle on and off creatine by taking loading doses of creatine monohydrate for 3 to 5 days every 3 to 4 weeks during training. Theoretically, since it takes 4 to 6 weeks for elevated creatine stores to return to baseline, this protocol would be effective in increasing and maintaining elevated creatine stores over time 1.

Effects of Creatine Supplementation on Muscle Creatine Stores
Numerous studies indicate that dietary supplementation of creatine monohydrate increases muscle creatine and phosphocreatine (PC) content by 10 to 40% 2,9. In simple terms, one can think of the normal creatine content of the muscle (about 120 grams) as being a gas tank that is 3/4 full. Creatine supplementation typically allows an individual to fill up their creatine storage tank up to 150 to 160 grams (i.e., 20 to 30%). It should be noted that the amount of creatine retained in the muscle following creatine supplementation depends on the amount of creatine in the muscle before supplementation. Individuals with low creatine content in muscle prior to supplementation may increase creatine stores by 20 to 40% while individuals with relatively high creatine levels before supplementation may only experience a 10 to 20% increase in muscle creatine content. Performance changes in response to creatine supplementation have been correlated with the magnitude of increase in muscle creatine levels. 10,11 Once creatine levels are elevated and an individual stops taking creatine, studies indicate it may take 4 to 6 weeks before creatine levels return to baseline.12 There is no evidence that muscle creatine levels fall below baseline after cessation of creatine supplementation, which might suggest a long-term suppression of endogenous creatine synthesis. 2,13

Theoretical Benefits of Creatine Supplementation
Increasing muscle availability of creatine and PC can affect exercise and training adaptations in several ways. First, increasing the availability of PC in the muscle may help maintain availability of energy during high intensity exercise, like sprinting and weightlifting. Second, increasing the availability of PC may help speed recovery between sprints and/or bouts of intense exercise. These adaptations would allow an athlete to do more work over a series of sprints and/or sets of exercise theoretically leading to greater gains in strength, muscle mass, and/or performance over time. For this reason, creatine supplementation has primarily been recommended as an ergogenic aid for power/strength athletes. However, recent research indicates that endurance athletes may also benefit from creatine supplementation. In this regard, studies indicate creatine loading prior to carbohydrate loading promotes greater glycogen retention 14. Additionally, studies indicate that ingesting creatine with carbohydrate during carbohydrate loading promotes greater creatine and glycogen retention 15-18. Theoretically, this may improve glycogen availability for endurance athletes. Creatine has also been shown to improve repetitive sprint performance. Since endurance athletes employ interval training techniques in an attempt to improve speed and anaerobic threshold, creatine supplementation during training may improve interval training adaptations leading to improved performance. Finally, studies also indicate that creatine supplementation can help maintain body weight and muscle mass during training. Since many endurance athletes have difficulty maintaining body mass during training, creatine supplementation may help maintain optimal body composition.

Effects of Creatine on Exercise Performance or Training Adaptations
As of this writing, there have been more than one thousand articles published in the peer-reviewed scientific literature on creatine supplementation. Slightly over half of these studies have evaluated the effects of creatine supplementation on exercise performance. The majority of these studies (about 70%) indicate that creatine supplementation promotes a statistically significant improvement in exercise capacity 6. This means that 95 times out of 100, if you take creatine as described in the study, you will experience an improvement in exercise performance. The average gain in performance from these studies typically ranges between 10 to 15%. For example, short-term creatine supplementation has been reported to improve maximal power/strength (5-15%), work performed during sets of maximal-effort muscle contractions (5-15%), single-effort sprint performance (1-5%), and work performed during repetitive sprint performance (5-15%).6 Long-term creatine supplementation appears to enhance the quality of training generally leading to 5 to 15% greater gains in strength and performance.6 Nearly all studies indicate that creatine supplementation increases body mass by about 1 to 2 kg in the first week of loading.6 In training studies, subjects taking creatine typically gain twice as much body mass and/or fat free mass (i.e., an extra 2 to 4 pounds of muscle mass during 4 to 12 weeks of training) than subjects taking a placebo. No study has reported that creatine supplementation significantly impairs exercise capacity. Although all studies do not report significant results, the preponderance of scientific evidence indicates that creatine supplementation appears to be an effective nutritional ergogenic aid for a variety of exercise tasks in a number of athletic and clinical populations.1,6 The following highlights some of the recent research that has evaluated the effects of short and long-term creatine supplementation on exercise performance and/or training adaptations.

Short-Term Supplementation
Numerous studies have been conducted to evaluate the effects of short-term creatine supplementation (3-7 days) on exercise performance. For example, Volek and colleagues 19 reported that creatine supplementation (25 grams/day for 7 days) 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. Tarnopolsky and coworkers 20 reported creatine supplementation (20 grams/day x 4 days) increased peak cycling power, dorsi-flexion maximal voluntary contractions (MVC) torque, and lactate in men and women with no apparent gender effects. Moreover, Wiroth and colleagues 21 reported that creatine supplementation (15 grams/day x 5 days) significantly improved maximal power and work performed during 5 x 10-s cycling sprints with 60-s rest recovery in younger and older subjects.

Creatine supplementation has also been shown to improve exercise performance during various sport activities. For example, Skare and associates 22 reported that creatine supplementation (20 grams/day) decreased 100-m sprint times and reduced the total time of 6 x 60-m sprints in a group of well-trained adolescent competitive runners. Mujika and colleagues 23 reported that creatine supplementation (20 grams/day x 6 days) improved repeated sprint performance (6 x 15m sprints with 30-s recovery) and limited the decay in jumping ability in 17 highly trained soccer players. Similarly, Ostojic and coworkers 24 reported that creatine supplementation (30 grams/day for 7 days) improved soccer-specific skill performance in young soccer players. Theodorou et al 25 reported that creatine supplementation (25 grams/day x 4-days) significantly improved mean interval performance times in 22 elite swimmers. Mero and colleagues 26 reported that supplementation of creatine (20 grams/day) for 6-d combined with sodium bicarbonate (0.3 grams/kg) ingestion 2-h prior to exercise significantly improved 2x100m swim performance. Finally, Preen and associates 27 evaluated the effects of ingesting creatine (20 grams/day x 5 days) on resting and post-exercise creatine and PC content as well as performance of an 80-min intermittent sprint test (10 sets of 5-6 x 6-s sprints with varying recovery intervals). The authors reported that creatine increased resting and post-exercise creatine and PC content, mean work performed, and total work performed during 6 x 6-s sets with 54-s and 84-s recovery. In addition, work performed during 5 x 6-s sprints with 24-s recovery tended to be greater. Collectively, these findings and many others indicate that creatine supplementation can significantly improve performance of athletes in a variety of sport-related field activities.

Long-Term Supplementation. Theoretically, increasing the ability to perform high-intensity exercise may lead to greater training adaptations over time. Consequently, a number of studies have evaluated the effects of creatine supplementation on training adaptations. For example, Vandenberghe et al 1228 reported that creatine supplementation (20 grams/day x 5 days; 0.1 or 0.3 grams/kg/day of FFM x 51-d) in conjunction with resistance and speed/agility training significantly improved 40-yd dash time and bench press strength in 39 college athletes. Kreider and associates 29 reported that creatine supplementation (15.75 grams/day x 28-days) during off-season college football training promoted greater gains in FFM and repetitive sprint performance in comparison to subjects ingesting a placebo. Likewise, Stone et al 30 reported that 5-weeks of creatine ingestion (~10 or 20 grams/day with and without pyruvate) promoted significantly greater increases in body mass, FFM, 1 RM bench press, combined 1 RM squat and bench press, vertical jump power output, and peak rate of force development during in-season training in 42 Division IAA college football players.

Volek and coworkers 31 reported that 12-weeks of creatine supplementation (25 grams/day x 7 days; 5 grams/day x 77 days) during periodized resistance training increased muscle total creatine and PC, FFM, type I, IIa, and IIb muscle fiber diameter, bench press and squat 1 RM, and lifting volume (weeks 5-8) in 19 resistance-trained athletes. Kirksey and colleagues 32 found that creatine supplementation (0.3 grams/kg/day x 42 days) during off-season training promoted greater gains in vertical jump height and power, sprint cycling performance, and FFM in 36 Division IAA male and female track and field athletes. Moreover, Jones and collaborators 3334 reported that creatine supplementation (20 grams/day x 7 days; 10 grams/day x 14 days) significantly increased FFM and cumulative strength gains during training in 40 subjects initiating training. Additional gains were observed when 3 grams/day of calcium beta-hydroxy-beta-methylbutyrate (HMB) was co-ingested with creatine. Finally, Willoughby and associates 35 reported that in comparison to controls, creatine supplementation (6 grams/day x 12 weeks) during resistance training (6-8 repetitions at 85-90%; 3 x weeks) significantly increased total body mass, FFM, and thigh volume, 1 RM strength, myofibrillar protein content, Type I, IIa, and IIx myosin heavy chain (MHC) mRNA expression, and MHC protein expression. In a subsequent paper, Willoughby and colleagues 36 reported that Cr supplementation (6 grams/day x 12 weeks) increased M-CK mRNA expression apparently due to increases in the expression of myogenin and MRF-4. The researchers concluded that increases in myogenin and MRF-4 mRNA and protein may play a role in increasing myosin heavy chain expression. These data indicate that creatine supplementation can directly influence muscle protein synthesis. Collectively, these studies and others provide strong evidence that creatine supplementation during intense resistance training leads to greater gains in strength and muscle mass.

Possible Medical Uses of Creatine
Creatine and phosphocreatine are involved in numerous metabolic processes. Creatine synthesis deficiencies and/or abnormal availability of creatine and PC have been reported to cause a number of medical problems. For this reason, the potential medical uses of creatine have been investigated since the mid 1970s. Initially, research focused on the role of creatine and/or creatine phosphate in reducing heart arrhythmias and/or improving heart function during ischemia events (i.e., lack of oxygen) 1. Initial studies also evaluated the effects of treating various medical populations who had creatine deficiences (i.e., gyrate atrophy, infants and children with low levels of PC in the brain, etc). Interest in the potential medical uses of creatine has increased over the last ten years. Researchers have been particularly interested in determining whether creatine supplementation may reduce rates of atrophy and/or muscle wasting; speed the rate of recovery from musculoskeletal and/or spinal cord injuries; and improve strength and muscle endurance in patients with various neuromuscular diseases.1,2 For example, researchers have been evaluating whether creatine supplementation37-41 muscular dystrophy, 42-4445-49 Huntington's disease, 50-53 amyotrophic lateral sclerosis or Lou Gerhig's Disease, 54-57 arthritis, 58 diabetes, 59 high cholesterol and triglyceride levels, 29,60 and elevated homocysteine levels.61-64 Other studies have reported that creatine supplementation during training reduces injury rates in athletes 65-69 and/or allows athletes to tolerate intensified training to a greater degree.70 Although more research is needed, some promising results have been reported in a number of studies suggesting that creatine may have therapeutic benefits in certain patient populations.

Common Questions About Creatine reported that in comparison to a placebo group, creatine supplementation (20 grams/day x 4 days; 5 grams/day x 65 days) during 10-weeks of training in women increased total creatine and PC content, maximal strength (20-25%), maximal intermittent exercise capacity of the arm flexors (10-25%), and fat free mass (FFM) by 60%. In addition, the researchers reported that creatine supplementation during 10-weeks of detraining helped maintain training adaptations to a greater degree. Noonan and collaborators reported that creatine (20 grams/day x 5 days; 5 grams/day x 10 weeks) promoted greater gains in sprint performance (5 x 15-s with 15-s recovery) and average on-ice sprint performance (6 x 80-m sprints) in 16 elite ice-hockey players. Interestingly, Jowko et al may improve clinical outcomes in patients with brain and/or spinal cord injuries, myophathies,
Are There Any Side Effects from Creatine? The only side effect reported in the scientific and medical literature from creatine supplementation has been weight gain.1,2,71 However, there have been a number of anecdotally reported side effects reported in the popular literature such as gastrointestinal distress, muscle cramping, dehydration, and increased risk to musculoskeletal injury (i.e., muscle strains/pulls). Additionally, there has also been concern that short and/or long-term creatine supplementation may increase renal stress and/or adversely affect the muscles, liver, or other organs of the body. Over the last few years a number of studies have attempted to assess the medical safety of creatine. These studies indicate that creatine is not associated with any of these anecdotally reported problems.66,72-80 In fact, there is recent evidence that creatine may lessen heat stress and reduce the susceptibility to musculoskeletal injuries among athletes engaged in trainin.66,79,80 While people who take creatine may experience some of these problems, the incidence of occurrence in creatine users does not appear to be greater than subjects who take placebos and in some cases have been reported to be less.73

What is the Best Form of Creatine to Take? Nearly all studies on creatine supplementation have evaluated pharmacuetical grade creatine monohydrate in powder form or have used oral or intravenous phosphocreatine formulations (a more expensive form of creatine). However, since creatine has become a popular supplement, there are a number of different forms of creatine that have been marketed (e.g., creatine candy/bars, liquid creatine, creatine gum, creatine citrate, effervescent creatine, etc). Many of these forms of creatine claim to be better than creatine monohydrate. However, I am aware of no data that indicates that any of these forms of creatine increases creatine uptake to the muscle better than creatine monohydrate. In fact, a recent study from my lab indicated that liquid creatine has no effect on muscle creatine store.81 A few published studies have compared the ergogenic value of several of these types of supplements to creatine monohydrate. However, results have generally indicated that although some of these supplements (i.e., creatine candy, creatine gum, and effervescent creatine) can improve exercise capacity, they do not appear to work any better than creatine monohydrate. Consequently, the only potential benefits that I see from many of these different forms of creatine are convenience, supplement variety, and/or taste preferences. The greatest disadvantage, however, is that many of these supplements are more expensive than creatine monohydrate. There is absolutely no evidence that you can take less of these types of supplements (e.g., liquid creatine or effervescent creatine) and get the same benefits as you would by ingesting higher amounts of creatine monohydrate, due to less degradation in the stomach, greater intestinal absorption, faster absorption in the blood, and/or greater muscle uptake. Finally, there are three primary sources for creatine (Germany, the U.S., and China). Independent testing has revealed that Chinese sources of creatine may have less purity and/or contain higher amounts of contaminants like dicyandiamide, dihydrotriazine, and/or creatinine (converted form of creatine). The best raw sources of creatine monohydrate appear to be from Germany (e.g., AlzChem CreaPure