1  Journal of the International Society of Sports Nutrition 201714:18


International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine


Richard B. Kreider, Douglas S. Kalman, Jose Antonio, Tim N. Ziegenfuss, Robert Wildman,Rick Collins, Darren G. Candow, Susan M. Kleiner, Anthony L. Almada and Hector L. Lopez



Creatine is one of the most popular nutritional ergogenic aids for athletes. Studies have consistently shown that creatine supplementation increases intramuscular creatine concentrations which may help explain the observed improvements in high intensity exercise performance leading to greater training adaptations. In addition to athletic and exercise improvement, research has shown that creatine supplementation may enhance post-exercise recovery, injury prevention, thermoregulation, rehabilitation, and concussion and/or spinal cord neuroprotection. Additionally, a number of clinical applications of creatine supplementation have been studied involving neurodegenerative diseases (e.g., muscular dystrophy, Parkinson’s, Huntington’s disease), diabetes, osteoarthritis, fibromyalgia, aging, brain and heart ischemia, adolescent depression, and pregnancy. These studies provide a large body of evidence that creatine can not only improve exercise performance, but can play a role in preventing and/or reducing the severity of injury, enhancing rehabilitation from injuries, and helping athletes tolerate heavy training loads. Additionally, researchers have identified a number of potentially beneficial clinical uses of creatine supplementation. These studies show that short and long-term supplementation (up to 30 g/day for 5 years) is safe and well-tolerated in healthy individuals and in a number of patient populations ranging from infants to the elderly. Moreover, significant health benefits may be provided by ensuring habitual low dietary creatine ingestion (e.g., 3 g/day) throughout the lifespan. The purpose of this review is to provide an update to the current literature regarding the role and safety of creatine supplementation in exercise, sport, and medicine and to update the position stand of International Society of Sports Nutrition (ISSN).

You can access the full article at https://jissn.biomedcentral.com/articles/10.1186/s12970-017-0173-z


2) Med Sci Sports Exerc. 2000 Mar;32(3):654-8.

Effects of oral creatine supplementation on muscular strength and body composition.

Becque MD1Lochmann JDMelrose DR.



The purpose of this investigation was to examine the effects of 6 wk of oral creatine supplementation during a periodized program of arm flexor strength training on arm flexor IRM, upper arm muscle area, and body composition.


Twenty-three male volunteers with at least 1 yr of weight training experience were assigned in a double blind fashion to two groups (Cr, N = 10; Placebo, N = 13) with no significant mean pretest one repetition maximum (IRM) differences in arm flexor strength. Cr ingested 5 g of creatine monohydrate in a flavored, sucrose drink four times per day for 5 d. After 5 d, supplementation was reduced to 2 g x d(-1). Placebo ingested a flavored, sucrose drink. Both drinks were 500 mL and made with 32 g of sucrose. IRM strength of the arm flexors, body composition, and anthropometric upper arm muscle area (UAMA) were measured before and after a 6-wk resistance training program. Subjects trained twice per week with training loads that began at 6RM and progressed to 2RM.


IRM for Cr increased (P < 0.01) from (mean +/- SD) 42.8 +/- 17.7 kg to 54.7 +/- 14.1 kg, while IRM for Placebo increased (P < 0.01) from 42.5 +/- 15.9 kg to 49.3 +/- 15.7 kg. At post-test IRM was significantly (P < 0.01) greater for Cr than for Placebo. Body mass for Cr increased (P < 0.01) from 86.7 +/- 14.7 kg to 88.7 +/- 13.8 kg. Fat-free mass for Cr increased (P < 0.01) from 71.2 +/- 10.0 kg to 72.8 +/- 10.1 kg. No changes in body mass or fat-free mass were found for Placebo. There were no changes in fat mass and percent body fat for either group. UAMA increased (P < 0.01) 7.9 cm2 for Cr and did not change for Placebo.


Creatine supplementation during arm flexor strength training lead to greater increases in arm flexor muscular strength, upper arm muscle area, and fat-free mass than strength training alone.


3 Mol Cell Biochem.2003 Feb;244(1-2):89-94.

Effects of creatine supplementation on performance and training adaptations.

Kreider RB1.


Creatine has become a popular nutritional supplement among athletes. Recent research has also suggested that there may be a number of potential therapeutic uses of creatine. This paper reviews the available research that has examined the potential ergogenic value of creatine supplementation on exercise performance and training adaptations. Review of the literature indicates that over 500 research studies have evaluated the effects of creatine supplementation on muscle physiology and/or exercise capacity in healthy, trained, and various diseased populations. Short-term creatine supplementation (e.g. 20 g/day for 5-7 days) has typically been reported to increase total creatine content by 10-30% and phosphocreatine stores by 10-40%. Of the approximately 300 studies that have evaluated the potential ergogenic value of creatine supplementation, about 70% of these studies report statistically significant results while remaining studies generally report non-significant gains in performance. No study reports a statistically significant ergolytic effect. 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%). Moreover, creatine supplementation during training has been reported to promote significantly greater gains in strength, fat free mass, and performance primarily of high intensity exercise tasks. Although not all studies report significant results, the preponderance of scientific evidence indicates that creatine supplementation appears to be a generally effective nutritional ergogenic aid for a variety of exercise tasks in a number of athletic and clinical populations.


4) J Am Diet Assoc. 1997 Jul;97(7):765-70.

Creatine supplementation enhances muscular performance during high-intensity resistance exercise.

Volek JS1Kraemer WJBush JABoetes MIncledon TClark KLLynch JM.



This study was undertaken to investigate the influence of oral supplementation with creatine monohydrate on muscular performance during repeated sets of high-intensity resistance exercise.


Fourteen active men were randomly assigned in a double-blind fashion to either a creatine group (n = 7) or a placebo group (n = 7). Both groups performed a bench press exercise protocol (5 sets to failure using each subject’s predetermined 10-repetition maximum) and a jump squat exercise protocol (5 sets of 10 repetitions using 30% of each subject’s 1-repetition maximum squat) on three different occasions (T1, T2, and T3) separated by 6 days.


Before T1, both groups received no supplementation. From T1 to T2, both groups ingested placebo capsules. From T2 to T3, the creatine group ingested 25 g creatine monohydrate per day, and the placebo group ingested an equivalent amount of placebo.


Total repetitions for each set of bench presses and peak power output for each set of jump squats were determined. Other measures included assessment of diet, body mass, skinfold thickness, and preexercise and 5-minute postexercise lactate concentrations.


Lifting performance was not altered for either exercise protocol after ingestion of the placebos. Creatine supplementation resulted in a significant improvement in peak power output during all 5 sets of jump squats and a significant improvement in repetitions during all 5 sets of bench presses. After creatine supplementation, postexercise lactate concentrations were significantly higher after the bench press but not the jump squat. A significant increase in body mass of 1.4 kg (range = 0.0 to 2.7 kg) was observed after creatine ingestion.


One week of creatine supplementation (25 g/day) enhances muscular performance during repeated sets of bench press and jump squat exercise.


5) Mol Cell Endocrinol. 2010 Apr 12;317(1-2):25-30.

Effects of oral creatine and resistance training on serum myostatin and GASP-1.

Saremi A1Gharakhanloo RSharghi SGharaati MRLarijani BOmidfar K.


Myostatin is a catabolic regulator of skeletal muscle mass. The purpose of this study was to determine the effect of resistance training for 8 weeks in conjunction with creatine supplementation on muscle strength, lean body mass, and serum levels of myostatin and growth and differentiation factor-associated serum protein-1 (GASP-1). In a double-blinded design 27 healthy male subjects (23.42+/-2.2 years) were assigned to control (CON), resistance training+placebo (RT+PL) and resistance training+creatine supplementation (RT+CR) groups. The protocol consisted of 3 days per week of training for 8 weeks, each session including three sets of 8-10 repetitions at 60-70% of 1 RM for whole-body exercise. Blood sampling, muscular strength testing and body composition analysis (full body DEXA) were performed at 0, 4th and 8th weeks. Myostatin and GASP-1 was measured. Resistance training caused significant decrease in serum levels of myostatin and increase in that of GASP-1. Creatine supplementation in conjunction with resistance training lead to greater decreases in serum myostatin (p<0.05), but had not additional effect on GASP-1 (p>0.05). The effects of resistance training on serum levels of myostatin and GASP-1, may explain the increased muscle mass that is amplified by creatine supplementation.


6)  J Athl Train. 2003 Jan-Mar; 38(1): 44–50.

Creatine Supplementation Increases Total Body Water Without Altering Fluid Distribution

Michael E. Powers,* Brent L. Arnold, Arthur L. Weltman, David H. Perrin,§ Dilawaar Mistry, David M. Kahler,William Kraemer, and Jeff Volek




To examine the effects of oral creatine (Cr) monohydrate supplementation on muscle Cr concentration, body mass, and total body water (TBW), extracellular water (ECW), and intracellular water (ICW) volumes.

Design and Setting:

After an overnight fast, urinary Cr and creatinine concentrations, muscle Cr concentration, body mass, TBW, ECW, and ICW were measured, and subjects were randomly assigned to either a Cr or a placebo (P) group. The Cr group ingested 25 g/d of Cr for 7 days (loading phase) and 5 g/d for the remaining 21 days (maintenance phase), whereas the P group ingested a sucrose P using the same protocol. All the measures were reassessed immediately after the loading and maintenance phases.


Sixteen men (age = 22.8 ± 3.01 years, height = 179.8 ± 7.1 cm, body mass = 84.8 ± 11.2 kg) and 16 women (age = 21.8 ± 2.51 years, height = 163.4 ± 5.9 cm, body mass = 63.6 ± 14.0 kg) involved in resistance training volunteered to participate in this study.


Muscle Cr concentration was determined from the vastus lateralis muscle using a percutaneous needle-biopsy technique. Total body water, ECW, and ICW volumes were assessed using deuterium oxide and sodium bromide dilution analyses.


The Cr group experienced a significant increase in muscle Cr concentration, body mass, and TBW. The P group experienced a small but significant increase in TBW only.


The Cr supplementation protocol was effective for increasing muscle Cr concentrations, body mass, and TBW; however, fluid distribution was not changed.



7)  Int J Sport Nutr Exerc Metab. 2008 Aug;18(4):389-98.

Effect of creatine supplementation and resistance-exercise training on muscle insulin-like growth factor in young adults.

Burke DG1Candow DGChilibeck PDMacNeil LGRoy BDTarnopolsky MAZiegenfuss T.


The purpose of this study was to compare changes in muscle insulin-like growth factor-I (IGF-I) content resulting from resistance-exercise training (RET) and creatine supplementation (CR). Male (n=24) and female (n=18) participants with minimal resistance-exercise-training experience (=1 year) who were participating in at least 30 min of structured physical activity (i.e., walking, jogging, cycling) 3-5 x/wk volunteered for the study. Participants were randomly assigned in blocks (gender) to supplement with creatine (CR: 0.25 g/kg lean-tissue mass for 7 days; 0.06 g/kg lean-tissue mass for 49 days; n=22, 12 males, 10 female) or isocaloric placebo (PL: n=20, 12 male, 8 female) and engage in a whole-body RET program for 8 wk. Eighteen participants were classified as vegetarian (lacto-ovo or vegan; CR: 5 male, 5 female; PL: 3 male, 5 female). Muscle biopsies (vastus lateralis) were taken before and after the intervention and analyzed for IGF-I using standard immunohistochemical procedures. Stained muscle cross-sections were examined microscopically and IGF-I content quantified using image-analysis software. Results showed that RET increased intramuscular IGF-I content by 67%, with greater accumulation from CR (+78%) than PL (+54%; p=.06). There were no differences in IGF-I between vegetarians and nonvegetarians. These findings indicate that creatine supplementation during resistance-exercise training increases intramuscular IGF-I concentration in healthy men and women, independent of habitual dietary routine.


8)  J Sports Med Phys Fitness. 1999 Sep;39(3):189-96.

Oral creatine supplementation improves multiple sprint performance in elite ice-hockey players.

Jones AM1Atter TGeorg KP.



The purpose of this study was to assess the effect of oral creatine monohydrate supplementation on multiple sprint cycle and skating performance in ice-hockey players.



sixteen elite ice-hockey players were selected as subjects.


subjects were randomly assigned to either a creatine (Cr) (n = 8) or a placebo (P) group (n = 8) in a double blind design. After familiarization and baseline tests, subjects loaded with 5 g of creatine monohydrate or placebo (glucose) four times per day for 5 days, after which a maintenance dose of 5 g per day for 10 weeks was administered. At baseline, and after 10 days and 10 weeks of supplementation, subjects performed i) a cycle test involving 5 all-out sprints of 15 sec duration separated by 15 sec recovery with the resistance set at 0.075 body mass (kg), and ii) 6 timed 80-m skating sprints with the sprints initiated every 30 sec and a split time taken at 47 m.


A two-way ANOVA demonstrated no significant change in any of the variables in the P group over the period of study. However, in the Cr group, average mean power output over the 5 sprints was significantly higher at 10 days (1074 +/- 241 W) and 10 weeks (1025 +/- 216 W) than at baseline (890 +/- 172 W), (p < 0.01). Average peak power output over the 5 sprints improved significantly from baseline (1294 +/- 311 W) to 10 days (1572 +/- 463 W), (p < 0.01). Average on-ice sprint performance to 47 m was significantly faster at 10 days (6.88 +/- 0.21 sec) and 10 weeks (6.96 +/- 0.19 sec) than at baseline (7.17 +/- 0.27 sec), (p < 0.005).


This study demonstrates that creatine supplementation has an ergogenic effect in elite ice-hockey players.


9)  J Int Soc Sports Nutr. 2007 Nov 26;4:20.

Effects of creatine loading on electromyographic fatigue threshold during cycle ergometry in college-aged women.

Smith AE1Walter AAHerda TJRyan EDMoon JRCramer JTStout JR.


The purpose of this study was to examine the effects of 5 days of Creatine (Cr) loading on the electromyographic fatigue threshold (EMGFT) in college-aged women. Fifteen healthy college-aged women (mean +/- SD = 22.3 +/- 1.7 yrs) volunteered to participate in this double-blind, placebo-controlled study and were randomly placed into either placebo (PL – 10 g of flavored dextrose powder; n = 8) or creatine (Cr – 5 g di-creatine citrate plus 10 g of flavored dextrose powder; n = 7; Creatine Edge, FSI Nutrition) loading groups. Each group ingested one packet 4 times per day (total of 20 g/day) for 5 days. Prior to and following supplementation, each subject performed a discontinuous incremental cycle ergometer test to determine their EMGFT value, using bipolar surface electrodes placed on the longitudinal axis of the right vastus lateralis. Subjects completed a total of four, 60 second work bouts (ranging from 100-350 W). The EMG amplitude was averaged over 10 second intervals and plotted over the 60 second work bout. The resulting slopes from each successive work bouts were used to calculate EMGFT. A two-way ANOVA (group [Cr vs. PL] x time [pre vs. post]) resulted in a significant (p = 0.031) interaction. Furthermore, a dependent samples t-test showed a 14.5% +/- 3.5% increase in EMGFT from pre- to post-supplementation with Cr (p = 0.009), but no change for the PL treatment (-2.2 +/- 5.8%; p = 0.732). In addition, a significant increase (1.0 +/- 0.34 kg; p = 0.049) in weight (kg) was observed in the Cr group but no change for PL (-0.2 kg +/- 0.2 kg). These findings suggest that 5 days of Cr loading in women may be an effective strategy for delaying the onset of neuromuscular fatigue during cycle ergometry.


10)  Amino Acids. 2008 Feb;34(2):245-50.

Effects of creatine supplementation on glucose tolerance and insulin sensitivity in sedentary healthy males undergoing aerobic training.

Gualano B1Novaes RBArtioli GGFreire TOCoelho DFScagliusi FBRogeri PSRoschel HUgrinowitsch CLancha AH Jr.


Recent findings have indicated that creatine supplementation may affect glucose metabolism. This study aimed to examine the effects of creatine supplementation, combined with aerobic training, on glucose tolerance in sedentary healthy male. Subjects (n = 22) were randomly divided in two groups and were allocated to receive treatment with either creatine (CT) ( approximately 10 g . day over three months) or placebo (PT) (dextrose). Administration of treatments was double blind. Both groups underwent moderate aerobic training. An oral glucose tolerance test (OGTT) was performed and both fasting plasma insulin and the homeostasis model assessment (HOMA) index were assessed at the start, and after four, eight and twelve weeks. CT demonstrated significant decrease in OGTT area under the curve compared to PT (P = 0.034). There were no differences between groups or over time in fasting insulin or HOMA. The results suggest that creatine supplementation, combined with aerobic training, can improve glucose tolerance but does not affect insulin sensitivity, and may warrant further investigation with diabetic subjects.



11)  Diabetes. 2001 Jan;50(1):18-23.

Effect of oral creatine supplementation on human muscle GLUT4 protein content after immobilization.

Op ‘t Eijnde B1Ursø BRichter EAGreenhaff PLHespel P.


The purpose of this study was to investigate the effect of oral creatine supplementation on muscle GLUT4 protein content and total creatine and glycogen content during muscle disuse and subsequent training. A double-blind placebo-controlled trial was performed with 22 young healthy volunteers. The right leg of each subject was immobilized using a cast for 2 weeks, after which subjects participated in a 10-week heavy resistance training program involving the knee-extensor muscles (three sessions per week). Half of the subjects received creatine monohydrate supplements (20 g daily during the immobilization period and 15 and 5 g daily during the first 3 and the last 7 weeks of rehabilitation training, respectively), whereas the other 11 subjects ingested placebo (maltodextrine). Muscle GLUT4 protein content and glycogen and total creatine concentrations were assayed in needle biopsy samples from the vastus lateralis muscle before and after immobilization and after 3 and 10 weeks of training. Immobilization decreased GLUT4 in the placebo group (-20%, P < 0.05), but not in the creatine group (+9% NS). Glycogen and total creatine were unchanged in both groups during the immobilization period. In the placebo group, during training, GLUT4 was normalized, and glycogen and total creatine were stable. Conversely, in the creatine group, GLUT4 increased by approximately 40% (P < 0.05) during rehabilitation. Muscle glycogen and total creatine levels were higher in the creatine group after 3 weeks of rehabilitation (P < 0.05), but not after 10 weeks of rehabilitation. We concluded that 1) oral creatine supplementation offsets the decline in muscle GLUT4 protein content that occurs during immobilization, and 2) oral creatine supplementation increases GLUT4 protein content during subsequent rehabilitation training in healthy subjects.


12)  Proc Biol Sci. 2003 Oct 22; 270(1529): 2147–2150.

Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial.

Caroline RaeAlison L DigneySally R McEwan, and Timothy C Bates


Creatine supplementation is in widespread use to enhance sports-fitness performance, and has been trialled successfully in the treatment of neurological, neuromuscular and atherosclerotic disease. Creatine plays a pivotal role in brain energy homeostasis, being a temporal and spatial buffer for cytosolic and mitochondrial pools of the cellular energy currency, adenosine triphosphate and its regulator, adenosine diphosphate. In this work, we tested the hypothesis that oral creatine supplementation (5 g d(-1) for six weeks) would enhance intelligence test scores and working memory performance in 45 young adult, vegetarian subjects in a double-blind, placebo-controlled, cross-over design. Creatine supplementation had a significant positive effect (p < 0.0001) on both working memory (backward digit span) and intelligence (Raven’s Advanced Progressive Matrices), both tasks that require speed of processing. These findings underline a dynamic and significant role of brain energy capacity in influencing brain performance.



13) ) Neuropsychol Dev Cogn B Aging Neuropsychol Cogn. 2007 Sep;14(5):517-28.

Creatine supplementation and cognitive performance in elderly individuals.

McMorris T1Mielcarz GHarris RCSwain JPHoward A.


The purpose of this study was to examine the effect of creatine supplementation on the cognitive performance of elderly people. Participants were divided into two groups, which were tested on random number generation, forward and backward number and spatial recall, and long-term memory tasks to establish a baseline level. Group 1 (n = 15) were given 5 g four times a day of placebo for 1 week, followed by the same dosage of creatine for the second week. Group 2 (n = 17) were given placebo both weeks. Participants were retested at the end of each week. Results showed a significant effect of creatine supplementation on all tasks except backward number recall. It was concluded that creatine supplementation aids cognition in the elderly.


14)  Am J Phys Med Rehabil. 2001 Jan;80(1):38-43; quiz 44-6.

Resistance training and gait function in patients with Parkinson’s disease.

Scandalis TA1Bosak ABerliner JCHelman LLWells MR.



To determine whether patients with Parkinson’s disease who are enrolled in a resistance training program can gain strength similar to that of normal control subjects and whether these gains in strength would improve their gait function.


Subjects included 14 patients with mild-to-moderate Parkinson’s disease of either gender and six normal control subjects of similar age. The training consisted of an 8-wk course of resistance training twice per week, focused primarily on the lower limbs. The primary outcome measures consisted of exercise performance monitoring and quantitative gait analysis before and after the training course.


Both the patients with Parkinson’s disease and normal control subjects significantly increased their performance with resistance training. Subjects with Parkinson’s disease had gains in strength similar to those of normal elderly adults. Patients with Parkinson’s disease also had significant gains in stride length, walking velocity, and postural angles compared with pretreatment values.


Patients with mild-to-moderate Parkinson’s disease can obtain increases in performance or strength similar to that of normal adults of the same age in a resistance training program. Resistance training can produce functional improvements in gait and may, therefore, be useful as part of a physical rehabilitation and/or health maintenance program for patients with Parkinson’s disease.