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Eagle
Scientific Name: Creatine
Other Names: Creatine Citrate, Creatine Monohydrate, Creatine Phosphate
Who is this for?
Uses
After several prominent athletes acknowledged using it in the past few years, creatine is best known for possibly improving athletic performance. Although multiple studies have been conducted to assess the effect of creatine on exercise potential, results are mostly inconclusive. While muscles may become bigger when creatine is taken, the gain in size may be due mainly to more water being held in the cells of muscle tissue. Additionally, it is important to note that many of the studies were done in clinics or laboratory settings that do not necessarily duplicate conditions at actual athletic events. Most of the studies tested small groups of young, trained athletes who took many different doses and forms of creatine. In general, results of the studies show that creatine supplementation may offer younger individuals a benefit for improving repeated, intensive spurts of effort such as weight-lifting. Less apparent improvement or no effects occurred for more sustained exercise such as swimming laps. Based on the responses of some individuals, taking creatine may actually decrease the ability to maintain prolonged exercise. Results among older individuals were inconclusive with small benefits seen in some studies, but no exercise improvement in others.
Since the potential muscle-enhancing effect of creatine supplementation may affect all muscles in the body, it has also been studied for treating heart conditions and muscular disorders such as muscular dystrophy. Several small studies of individuals with heart failure have had mixed results. In some studies, creatine has appeared to have a direct effect on the heart, causing it to beat more forcefully. Other studies found no effect on the heart itself, although an increase in overall muscle strength was seen in many of the individuals receiving creatine supplements. Creatine may have been more beneficial for improving heart function when it was injected into a vein than when it was taken orally. For individuals with muscle-weakening conditions, results of studies are also inconsistent. Animal studies show that creatine may lessen the effects of Huntington's disease, a hereditary degenerative disorder of brain tissue. In studies of individuals with a rare genetic condition known as McArdle's disease, daily doses of creatine at 60 mg per Kg (about 2.2 pounds) of body weight seemed to improve muscle function and lessen muscle fatigue. Higher doses seemed to worsen the condition, however. McArdle's disease involves the inability to produce energy from chemicals stored in muscle tissue. Muscle symptoms of individuals with muscular dystrophy and similar conditions have also seemed to be reduced by creatinine. Creatine supplements appeared to be effective in preserving sight for individuals with gyrate atrophy, a very rare condition affecting the muscles of the eyes. The use of creatine in all these conditions is under study and much more needs to be learned before creatine is proved to be effective for any of them.
Creatine may have non-muscular effects as well. In laboratory and animal studies, creatine and substances derived from it have shown inhibitory effects against cancer. One early theory is that creatine prompts cancer cells to disintegrate, but the exact ways it might work are not understood. In other laboratory, animal, and human studies, supplemental creatine may have had a lowering effect on cholesterol levels. It is thought that creatine may affect the way the body breaks down and uses cholesterol from foods, but this theory has not been confirmed by adequate research findings. Very early results from a few additional studies suggest that creatine may protect nerves from damage by chemicals and diseases. This effect may make it useful for treating conditions such as Parkinson's disease. All of these potential uses for creatine need further study before they can be recommended.
When should I be careful taking it?
Precautions
Some evidence suggests that creatine may worsen kidney conditions.
Creatine supplements are not recommended for individuals under 18 years of age because too little is known about possible long term effects. In addition, creatine may have different effects for children and teenagers than it does for adults.
Not enough is known about how creatine might affect a developing fetus or an infant to recommend its use during pregnancy or while breast-feeding.
What side effects should I watch for?
Major Side Effects
In continuous high doses (20,000 mg per day or more), creatine may contribute to high blood pressure -- possibly from water-retention. Water accumulation may also affect the function of the heart, kidneys, or liver.
Conversely, dehydration may also be possible during the use of supplemental creatine. Although creatine has not been proved to cause dehydration, it pulls water into muscle tissue, potentially leaving less water available for other body functions. Signs of dehydration range from dry mouth to fatigue. If it is severe, dehydration may cause the heart to beat rapidly. Athletes taking creatine are advised to drink additional fluids during and after exercise.
Less Severe Side Effects
Because creatine attracts and holds water in muscle cells, using it also includes gaining weight. Average amounts of weight gain seen during studies were between one pound and 4 pounds during the initial 5 days (of 20,000 mg per day). Long-term use of creatine may increase weight even more.
Other side effects associated with taking creatine include:
What interactions should I watch for?
Prescription Drugs
Theoretically, creatine may cause kidney damage because its by-product, creatinine, is filtered through the kidneys into urine. If it is taken at the same time as prescription drugs that might also damage kidney tissues, the risk of kidney damage may increase. Classes of prescription drugs that might cause kidney damage include:
Non-prescription strengths of non-steroidal anti-inflammatory drugs (NSAIDs) such as Advil, Aleve, ibuprofen, Motrin, naproxen, and many others have a slight risk of causing kidney damage. If creatine, which might also damage the kidneys, is taken at the same time as an NSAID, the risk of kidney damage could increase.
Herbal Products
Ephedra has been removed from the U.S. market. Its use is strongly discouraged. Individuals who take creatine and ephedra at the same time may have an increased risk of side effects. One case of a stroke has been reported in an individual who was taking several dietary supplements that included creatine and ephedra. The exact cause of the stroke is not known, but the combination of creatine and ephedra is best avoided.
Foods
Caffeine appears to cancel the exercise-enhancing effects of creatine when both are used together.
Some interactions between herbal products and medications can be more severe than others. The best way for you to avoid harmful interactions is to tell your doctor and/or pharmacist what medications you are currently taking, including any over-the-counter products, vitamins, and herbals. For specific information on how creatine interacts with drugs, other herbals, and foods and the severity of those interactions, please use our Drug Interactions Checker to check for possible interactions.
Should I take it?
Up to 2,000 mg (2 grams) of creatine are produced each day by the kidneys and liver. Another 1,000 mg to 2,000 mg (one gram to 2 grams) per day comes from the diet -- primarily from meat and fish. Creatine concentrates mostly in the large (skeletal) muscles, where it is involved in producing energy and moderating muscle fatigue. An adult of average weight (about 155 pounds) stores about 120,000 mg (120 grams) of creatine and uses about 2,000 mg (2 grams) every day. However, intensive exercise uses up creatine. It is believed that muscle stores of creatine are decreased dramatically during the first few seconds of exercise. Then, creatine stores gradually replenish over several minutes. As the muscles use energy, creatine is changed into a waste product known as creatinine, which is filtered into the urine by the kidneys. Creatine supplementation may increase the amount of creatine reserve up to 140,000 to 150,000 mg (140 grams to 150 grams), but any excess creatine is lost in the urine.
Supplemental creatine is manufactured artificially by reacting certain chemicals. It is usually sold as citrate, monohydrate, or phosphate salts, which may be easier for the body to use. Although some individuals feel that one salt is more beneficial than the others, no study evidence proves that any one of them works better than the others. Supplemental creatine should be labeled as "100% pure" or "free of impurities", because undesirable byproducts may be produced during manufacturing. Currently, the International Olympic Committee allows Olympic athletes to use creatine while competing in events.
Dosage and Administration
Creatine is available in a number of oral dose forms, with the most reliably consistent being capsules and powders that are usually added to water, low-acid fruit juice (such as apple, grape, pineapple, or tomato juice), or a sports drink that contains carbohydrates. Some research suggests that taking creatine with carbohydrates improves the absorption of creatine. Fruit juices with high acid contents (grapefruit, orange, and other citrus fruit juices) may interfere with the body's absorption of supplemental creatine. One teaspoon of most creatine powders supplies about 5,000 mg (5 grams). Many containers of creatine come with a scoop or spoon that is marked in dosage levels.
Note: Taking commercially-packaged liquid forms of creatine is not recommended due to the likelihood that creatine breaks down in solution.
Dosing for creatine varies depending on the desired effect. One general recommendation for enhancing exercise capability is to take a high dose of creatinine -- 20,000 mg (20 grams or about 4 teaspoons) per day for the first 2 to 7 days and then to reduce the daily dose to 2,000 mg (2 grams). Similar results have been seen with a dose of 3,000 mg (3 grams) every day. Usually, daily amounts of creatine are divided into two doses that are taken 10 to 12 hours apart.
Summary
Creatine is sold mainly to athletes and bodybuilders who want to increase muscle and improve exercise ability. Because it may strengthen muscle, creatine may be useful for degenerative heart and muscle conditions such as muscular dystrophy. Its potential effects on muscle-related diseases and other conditions remain to be proved.
Risks
Creatine is not recommended for individuals with kidney conditions or for children under the age of 18 years old. Pregnant and breast-feeding women are advised to avoid taking it, as well.
Side Effects
Although a definite connection has not been proved, a few individuals have died or experienced kidney collapse while taking creatine. Dehydration is possible and water retention probably will result in weight gain. Less serious side effects may be muscle-related (such as cramps) or gastrointestinal (such as diarrhea or nausea).
Interactions
Theoretically, creatine supplementation may increase the risk of kidney damage is it is taken at the same time as drugs such as certain antibiotics, cyclosporine, or NSAIDs that also may damage kidney tissue. The combination of ephedra and creatine may have adverse effects. Caffeine may cancel or reduce creatine's exercise-enhancing effects.
Last Revised May 26, 2004
References
Andreassen OA, Dedeoglu A, Ferrante RJ, et al. Creatine increase survival and delays motor symptoms in a transgenic animal model of Huntington's disease. Neurobiological Diseases. 2001;8(3):479-491.
Andrews R, Greenhaff P, Curtis S, Perry A, Cowley AJ . The effect of dietary creatine supplementation on skeletal muscle metabolism in congestive heart failure. European Heart Journal 1998;19(4):617-622.
Balsom PD, Soderland K, Ekblom B. Creatine in humans with special reference to creatine supplementation. Sports Medicine. 1994;18(4):268-280.
Balsom PD, Soderlund K, Sjodin B, Ekblom B. Skeletal muscle metabolism during short duration high-intensity exercise: influence of creatine supplementation. Acta Physiologica Scandinavia. 1995;154(3):303-310.
Barnett C, Hinds M, Jenkins DG. Effects of oral creatine supplementation on multiple sprint cycle performance. Australian Journal of Science and Medicine in Sports. 1996;28(1):35-39.
Bergnes G, Yuan W, Khandekar VS, et al. Creatine and phosphocreatine analogs: anticancer activity and enzymatic analysis. Oncology Research. 1996;8(3):121-130.
Bermon S, Venembre P, Sachet C, Valour S, Dolisi C. Effects of creatine monohydrate ingestion in sedentary and weight-trained older adults. Acta Physiologica Scandinavia. 1998;164(2):147-155.
Birch R, Noble D, Greenhaff PL. The influence of dietary creatine supplementation on performance during repeated bouts of maximal isokinetic cycling in man. European Journal of Applied Physiology. 1994;69(3):268-276.
Brose A, Parise G, Tarnopolsky MA. Creatine supplementation enhances isometric strength and body composition improvements following strength exercise training in older adults. Journals of Gerontology. Series A. Biological Sciences and Medical Sciences. 2003 Jan;58(1):11-19.
Brudnak MA. Creatine: are the benefits worth the risk? Toxicology Letters. 2004;150(1):123-130.
Chambers DJ, Haire K, Morley N, et al. St. Thomas' Hospital cardioplegia: enhanced protection with exogenous creatine phosphate. Annals of Thoracic Surgery. 1996;61(1):67-75.
Clarkson PM, Rawson ES. Nutritional supplements to increase muscle mass. Critical Reviews in Food Science and Nutrition. 1999;39(4):317-328.
ConsumerLab. Product review: muscular enhancement supplements: creatine, HM, and glutamine. Initial posting: September 24, 2003. Available at: http://www.consumerlab.com/results/creatine.asp. Accessed December 2, 2003.
Cooke WH, Barnes WS. The influence of recovery duration on high-intensity exercise performance after oral creatine supplementation. Canadian Journal of Applied Physiology. 1997;22(5):454-467.
Cooke WH, Grandjean PW, Barnes WS. Effect of oral creatine supplementation on power output and fatigue during bicycle ergometry. Journal of Applied Physiology. 1995;78(2):670-673.
Dawson B, Cutler M, Moody A, Lawrence S, Goodman C, Randall N. Effects of oral creatine loading on single and repeated maximal short sprints. Australian Journal of Science and Medicine in Sports. 1995;27(3):56-61.
Dedeoglu A, Kubilus JK, Yang L, Ferrante KL, Hersch SM, Beal MF, Ferrante RJ. Creatine therapy provides neuroprotection after onset of clinical symptoms in Huntington's disease transgenic mice. Journal of Neurochemistry. 2003;85(6):1359-1367.
Demant TW, Rhodes EC. Effects of creatine supplementation on exercise performance. Sports Medicine. 1999;28(1):49-60.
Dempsey RL, Mazzone MF, Meurer LN. Does oral creatine supplementation improve strength? A meta-analysis. Journal of Family Practice. 2002;51(11):945-951.
DesJardins M. Supplement use in the adolescent athlete. Current Sports Medicine Report. 2002;1(6):369-373.
Earnest CP, Almada AL, Mitchell TL. High-performance capillary electrophoresis-pure creatine monohydrate reduces blood lipids in men and women. Clinical Sciences. (London) 1996;91(1):113-118.
Farquhar WB, Zambraski EJ. Effects of creatine use on the athlete's kidney. Current Sports Medicine Report. 2002;1(2):103-106.
Febbraio MA, Flanagan TR, Snow RJ, et al. Effect of creatine supplementation on intramuscular TCr, metabolism and performance during intermittent, supramaximal exercise in humans. Acta Physiologica Scandinavia. 1995;155(4):387-395.
Ferraro S, Codella C, Palumbo F, et al. Hemodynamic effects of creatine phosphate in patients with congestive heart failure: a double-blind comparison trial versus placebo. Clinical Cardiology. 1996;19(9):699-703.
Francaux M, Poortmans JR. Effects of training and creatine supplement on muscle strength and body mass. European Journal of Applied Physiology. 1999;80(2):165-168.
Gordon A, Hultman E, Kaijser L, et al. Creatine supplementation in chronic heart failure increases skeletal muscle creatine phosphate and muscle performance. Cardiovascular Research. 1995;30(3):413-418.
Graham AS, Hatton RC. Creatine: a review of efficacy and safety. Journal of the American Pharmaceutical Association. (Washington) 1999;39(6):803-810.
Green AL, Simpson EJ, Littlewood JJ, Macdonald IA, Greenhaff PL. Carbohydrate ingestion augments creatine retention during creatine feeding in humans. Acta Physiologica Scandinavia. 1996;158(2):195-202.
Greenhaff P. Renal dysfunction accompanying oral creatine supplements. Lancet. 1998;352(9123):213-214.
Harris RC, Soderlund K, Hultman E. Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clinical Sciences. (London) 1992;83(3):367-374.
Heinanen K, Nanto-Salonen K, Komu M, et al. Creatine corrects muscle 31P spectrum in gyrate atrophy with hyperornithinaemia. European Journal of Clinical Investigation. 1999;29(12):1060-1065.
Heinanen K, Nanto-Salonen K, Komu M, et al. Muscle creatine phosphate in gyrate atrophy of the choroid and retina with hyperornithinaemia--clues to pathogenesis. European Journal of Clinical Investigation. 1999;29(5):426-431.
Hultman E, Soderlund K, Timmons JA, Cederblad G, Greenhaff PL. Muscle creatine loading in men. Journal of Applied Physiology. 1996;81(1):232-237.
Ingwall JS, Morales MF, Stockdale FE, Wildenthal K. Creatine: a possible stimulus skeletal cardiac muscle hypertrophy. Recent Advances in the Study of Cardiac Structure and Metabolism. 1975;8:467-481.
Jellin JM, Gregory P, Batz F, Hitchens K, et al, eds. Pharmacist's Letter/Prescriber's Letter. Natural Medicines Comprehensive Database, 3rd Edition. Stockton CA: Therapeutic Research Facility, 2000.
Jenkins MA. Creatine supplementation in athletes: review. SportsMed Web. 1998. Available at: http://www.rice.edu/~jenky/sports/creatine.html. Accessed May 26, 2004.
Jones AM, Atter T, Georg KP. Oral creatine supplementation improves multiple sprint performance in elite ice-hockey players. Journal of Sports Medicine and Physical Fitness. 1999;39(3):189-196.
Jowko E, Ostaszewski P, Jank M, et al. Creatine and beta-hydroxy-beta-methylbutyrate (HMB) additively increase lean body mass and muscle strength during a weight-training program. Nutrition. 2001;17(7-8):558-566.
Juhn MS. Oral creatine supplementation. Separating fact from hype. The Physician and Sports Medicine. 1999;27(5):232-234.
Juhn MS, Tarnopolsky M. Potential side effects of oral creatine supplementation: a critical review. Clinical Journal of Sports Medicine. 1998;8(4):298-304.
Kamber M, Koster M, Kreis R, Walker G, Boesch C, Hoppeler H. Creatine supplementation - part I: performance, clinical chemistry, and muscle volume. Medical Science in Sports and Exercise. 1999;31(12):1763-1769.
Kemper KJ. Creatine. The Longwood Herbal Task Force. Revised November 4, 1999. Available at: http://www.mcp.edu/herbal/creatine/creatine.pdf Accessed: December 1, 2003.
Klivenyi P, Calingasan NY, Starkov A, et al. Neuroprotective mechanisms of creatine occur in the absence of mitochondrial creatine kinase. Neurobiology of Disease. 2004;15(3):610-617.
Klivenyi P, Ferrante RJ, Matthews RT, et al. Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis. Nature Medicine. 1999;5(3):347-350.
Kocak S, Karli U. Effects of high dose oral creatine supplementation on anaerobic capacity of elite wrestlers. Journal of Sports Medicine and Physical Fitness. 2003;43(4):488-492.
Kreider RB. Effects of creatine supplementation on performance and training adaptations. Molecular and Cell Biochemistry. 2003;244(1-2):89-94.
Kreider RB, Ferreira M, Wilson M, et al. Effects of creatine supplementation on body composition, strength, and sprint performance. Medical Science in Sports and Exercise. 1998;30(1):73-82.
Kutz MR, Gunter MJ. Creatine monohydrate supplementation on body weight and percent body fat. Journal of Strength and Conditioning Research. 2003;17(4):817-821.
Leenders NM, Lamb DR, Nelson TE. Creatine supplementation and swimming performance. International Journal of Sports Nutrition. 1999;9(3):251-262.
Lillie JW, O'Keefe M, Valinski H, Hamlin HA Jr, Varban ML, Kaddurah-Daouk R. Cyclocreatine (1-carboxymethyl-2-iminoimidazolidine) inhibits growth of a broad spectrum of cancer cells derived from solid tumors. Cancer Research. 1993;53(13):3172-3178.
Lulinski, B. Creatine supplementation. Posted September 17, 1999. http://www.quackwatch.org/01Quackery.../creatine.html. Accessed May 26, 2004.
Martin KJ, Chen SF, Clark GM, et al. Evaluation of creatine analogues as a new class of anticancer agents using freshly explanted human tumor cells. Journal of the National Cancer Institute. 1994;86(8):608-613.
Matthews RT, Ferrante RJ, Klivenyi P, et al. Creatine and cyclocreatine attenuate MPTP neurotoxicity. Experimental Neurology. 1999;157(1):142-149.
Matthews RT, Yang L, Jenkins BG, et al. Neuroprotective effects of creatine and cyclocreatine in animal models of Huntington's disease. Journal of Neuroscience. 1998;18(1):156-163.
Maughan RJ, King DS, Lea T. Dietary supplements. Journal of Sports Science. 2004;22(1):95-113.
MedLine Plus. Dehydration. Updated August 21, 2003. Available at: http://www.nlm.nih.gov/medlineplus/e...cle/000982.htm. Accessed May 26, 2004.
Mendes RR, Tirapegui J. Creatine: the nutritional supplement for exercise - current concepts. [Article in Portuguese] Archivo Latinoamericano Nutrition. 2002;52(2):117-127.
Mihic S, MacDonald JR, McKenzie S, Tarnopolsky MA. Acute creatine loading increases fat-free mass, but does not affect blood pressure, plasma creatinine, or CK activity in men and women. Medical Science in Sports and Exercise. 2000;32(2):291-296.
Miller EE, Evans AE, Cohn M. Inhibition of rate of tumor growth by creatine and cyclocreatine. Proceedings of the National Academy of Sciences (USA). 1993;90:3304-3308.
Mujika I, Chatard J, Lacoste L, Barale F, Geyssant A. Creatine supplementation does not improve sprint performance in competitive swimmers. Medical Science in Sports and Exercise. 1996;28(11):1435-1441.
O'Dea JA. Consumption of nutritional supplements among adolescents: usage and perceived benefits. Health Education Research. 2003;18(1):98-107.
Odland LM, MacDougall JD, Tarnopolsky MA, Elorriaga A, Borgmann A. Effect of oral creatine supplementation on muscle [PCr] and short-term maximum power output. Medical Science in Sports and Exercise. 1997;29(2):216-219.
Palazzetti S, Rousseau AS, Richard MJ, Favier A, Margaritis I. Antioxidant supplementation preserves antioxidant response in physical training and low antioxidant intake. British Journal of Nutrition. 2004;91(1):91-100.
Persky AM, Muller M, Derendorf H, Grant M, Brazeau GA, Hochhaus G. Single- and multiple-dose pharmacokinetics of oral creatine. Journal of Clinical Pharmacology. 2003;43(1):29-37.
Poortmans JR, Auquier H, Renaut V, Durussel A, Saugy M, Brisson GR. Effect of short-term creatine supplementation on renal responses in men. European Journal of Applied Physiology. 1997;76(6):566-567.
Poortmans JR, Francaux M. Adverse effects of creatine supplementation: fact or fiction? Sports Medicine. 2000;30(3):155-170.
Poortmans JR, Francaux M. Long-term oral creatine supplementation does not impair renal function in healthy athletes. Medical Science in Sports and Exercise. 1999;31(8):1108-1110.
Preen D, Dawson B, Goodman C, Lawrence S, Beilby J, Ching S. Effect of creatine loading on long-term sprint exercise performance and metabolism. Medical Science in Sports and Exercise. 2001;33(5):814-821.
Prevost MC, Nelson AG, Morris GS. Creatine supplementation enhances intermittent work performance. Research Quarterly in Exercise and Sports. 1997;68(3):233-240.
Pritchard NR, Kalra PA. Renal dysfunction accompanying oral creatine supplements. Lancet. 1998;351(9111):1252-1253.
Rawson ES, Clarkson PM. Acute creatine supplementation in older men. International Journal of Sports Medicine. 2000;21(1):71-75.
Rawson ES, Volek JS. Effects of creatine supplementation and resistance training on muscle strength and weightlifting performance. Journal of Strength and Conditioning Research. 2003;17(4):822-831.
Rawson ES, Wehnert ML, Clarkson PM. Effects of 30 days of creatine ingestion in older men. European Journal of Applied Physiology. 1999;80(2):139-144.
Rico-Sanz J, Mendez Marco MT. Creatine enhances oxygen uptake and performance during alternating intensity exercise. Medical Science in Sports and Exercise. 2000;32(2):379-385.
Rossiter HB, Cannell ER, Jakeman PM. The effect of oral creatine supplementation on the 1000-m performance of competitive rowers. Journal of Sports Science. 1996;14(2):175-179.
Schilling BK, Stone MH, Utter A, et al. Creatine supplementation and health variables: a retrospective study. Medical Science in Sports and Exercise. 2001;33(2):183-188.
Sipila I, Rapola J, Simell O, Vannas A. Supplementary creatine as a treatment for gyrate atrophy of the choroid and retina. New England Journal of Medicine. 1981;304(15):867-870.
Snow RJ, McKenna MJ, Selig SE, Kemp J, Stathis CG, Zhao S. Effect of creatine supplementation on sprint exercise performance and muscle metabolism. Journal of Applied Physiology. 1998;84(5):1667-1673.
Tarnopolsky MA. Potential benefits of creatine monohydrate supplementation in the elderly. Current Opinion in Clinical Nutrition and Metabolic Care. 2000;3(6):497-502.
Tarnopolsky MA, Beal MF. Potential for creatine and other therapies targeting cellular energy dysfunction in neurological disorders. Annals of Neurology. 2001;49(5):561-574.
Tarnopolsky M, Martin J. Creatine monohydrate increases strength in patients with neuromuscular disease. Neurology. 1999;52(4):854-857.
Tarnopolsky MA, MacLennan DP. Creatine monohydrate supplementation enhances high-intensity exercise performance in males and females. International Journal of Sports Nutrition, Exercise and Metabolism. 2000;10(4):452-463.
Terjung RL, Clarkson P, Eichner ER, et al. The American College of Sports Medicine Roundtable on the physiological and health effects of oral creatine supplementation. Medical Science in Sports and Exercise. 2000;32(3):706-717.
Theodorou AS, Cooke CB, King RF, et al. The effect of longer-term creatine supplementation on elite swimming performance after an acute creatine loading. Journal of Sports Science. 1999;17(11):853-859.
Vahedi K, Domingo V, Amarenco P, Bousser MG. Ischemic stroke in a sportsman who consumed ma huang extract and creatine monohydrate for bodybuilding. Journal of Neurology, Neurosurgery and Psychiatry. 2000;68:112-113.
Vanakoski J, Kosunen V, Meririnne E, Seppala T. Creatine and caffeine in anaerobic and aerobic exercise: effects on physical performance and pharmacokinetic considerations. International Journal of Clinical Pharmacology and Therapeutics. 1998;36(5):258-262.
Vandeberghe K, Gillis N, Van Leemputte M, Van Hecke P, Vanstapel F, Hespel P. Caffeine counteracts the ergogenic action of muscle creatine loading. Journal of Applied Physiology. 1996;80(2):452-457.
Vandeberghe K, Goris M, Van Hecke P, Van Leemputte M, Vangerven L, Hespel P. Long-term creatine intake is beneficial to muscle performance during resistance training. Journal of Applied Physiology. 1997;83(6):2055-2063.
van Loon LJ, Oosterlaar AM, Hartgens F, Hesselink MK, Snow RJ, Wagenmakers AJ. Effects of creatine loading and prolonged creatine supplementation on body composition, fuel selection, sprint and endurance performance in humans. Clinical Sciences. (London). 2003;104(2):153-162.
Vannas-Sulonen K, Sipila I, Vannas A, Simell O, Rapola J. Gyrate atrophy of the choroid and retina. A five-year follow-up of creatine supplementation. Ophthalmology. 1985;92(12):1719-1727.
Volek JS, Ratamess NA, Rubin MR, et al. The effects of creatine supplementation on muscular performance and body composition responses to short-term resistance training overreaching. European Journal of Applied Physiology. Published online December 18, 2003.
Vorgerd M, Grehl T, Jager M, et al. Creatine therapy in myophosphorylase deficiency (McArdle disease): a placebo-controlled crossover trial. Archives of Neurology. 2000;57(7):956-963.
Vorgerd M, Zange J, Kley R, et al. Effect of high-dose creatine therapy on symptoms of exercise intolerance in McArdle disease: double-blind, placebo-controlled crossover study. Archives of Neurology. 2002;59(1):97-101.
Walter MC, Lochmuller H, Reilich P, et al. Creatine monohydrate in muscular dystrophies: A double-blind, placebo-controlled clinical study. Neurology. 2000;54(9):1848-1850.
Williams MH, Branch JD. Creatine supplementation and exercise performance: an update. Journal of the American College of Nutrition. 1998;173):216-234.
Last Revised May 26, 2004
Eagle
Scientific Name: Creatine
Other Names: Creatine Citrate, Creatine Monohydrate, Creatine Phosphate
Who is this for?
Uses
After several prominent athletes acknowledged using it in the past few years, creatine is best known for possibly improving athletic performance. Although multiple studies have been conducted to assess the effect of creatine on exercise potential, results are mostly inconclusive. While muscles may become bigger when creatine is taken, the gain in size may be due mainly to more water being held in the cells of muscle tissue. Additionally, it is important to note that many of the studies were done in clinics or laboratory settings that do not necessarily duplicate conditions at actual athletic events. Most of the studies tested small groups of young, trained athletes who took many different doses and forms of creatine. In general, results of the studies show that creatine supplementation may offer younger individuals a benefit for improving repeated, intensive spurts of effort such as weight-lifting. Less apparent improvement or no effects occurred for more sustained exercise such as swimming laps. Based on the responses of some individuals, taking creatine may actually decrease the ability to maintain prolonged exercise. Results among older individuals were inconclusive with small benefits seen in some studies, but no exercise improvement in others.
Since the potential muscle-enhancing effect of creatine supplementation may affect all muscles in the body, it has also been studied for treating heart conditions and muscular disorders such as muscular dystrophy. Several small studies of individuals with heart failure have had mixed results. In some studies, creatine has appeared to have a direct effect on the heart, causing it to beat more forcefully. Other studies found no effect on the heart itself, although an increase in overall muscle strength was seen in many of the individuals receiving creatine supplements. Creatine may have been more beneficial for improving heart function when it was injected into a vein than when it was taken orally. For individuals with muscle-weakening conditions, results of studies are also inconsistent. Animal studies show that creatine may lessen the effects of Huntington's disease, a hereditary degenerative disorder of brain tissue. In studies of individuals with a rare genetic condition known as McArdle's disease, daily doses of creatine at 60 mg per Kg (about 2.2 pounds) of body weight seemed to improve muscle function and lessen muscle fatigue. Higher doses seemed to worsen the condition, however. McArdle's disease involves the inability to produce energy from chemicals stored in muscle tissue. Muscle symptoms of individuals with muscular dystrophy and similar conditions have also seemed to be reduced by creatinine. Creatine supplements appeared to be effective in preserving sight for individuals with gyrate atrophy, a very rare condition affecting the muscles of the eyes. The use of creatine in all these conditions is under study and much more needs to be learned before creatine is proved to be effective for any of them.
Creatine may have non-muscular effects as well. In laboratory and animal studies, creatine and substances derived from it have shown inhibitory effects against cancer. One early theory is that creatine prompts cancer cells to disintegrate, but the exact ways it might work are not understood. In other laboratory, animal, and human studies, supplemental creatine may have had a lowering effect on cholesterol levels. It is thought that creatine may affect the way the body breaks down and uses cholesterol from foods, but this theory has not been confirmed by adequate research findings. Very early results from a few additional studies suggest that creatine may protect nerves from damage by chemicals and diseases. This effect may make it useful for treating conditions such as Parkinson's disease. All of these potential uses for creatine need further study before they can be recommended.
When should I be careful taking it?
Precautions
Some evidence suggests that creatine may worsen kidney conditions.
Creatine supplements are not recommended for individuals under 18 years of age because too little is known about possible long term effects. In addition, creatine may have different effects for children and teenagers than it does for adults.
Not enough is known about how creatine might affect a developing fetus or an infant to recommend its use during pregnancy or while breast-feeding.
What side effects should I watch for?
Major Side Effects
In continuous high doses (20,000 mg per day or more), creatine may contribute to high blood pressure -- possibly from water-retention. Water accumulation may also affect the function of the heart, kidneys, or liver.
Conversely, dehydration may also be possible during the use of supplemental creatine. Although creatine has not been proved to cause dehydration, it pulls water into muscle tissue, potentially leaving less water available for other body functions. Signs of dehydration range from dry mouth to fatigue. If it is severe, dehydration may cause the heart to beat rapidly. Athletes taking creatine are advised to drink additional fluids during and after exercise.
Less Severe Side Effects
Because creatine attracts and holds water in muscle cells, using it also includes gaining weight. Average amounts of weight gain seen during studies were between one pound and 4 pounds during the initial 5 days (of 20,000 mg per day). Long-term use of creatine may increase weight even more.
Other side effects associated with taking creatine include:
- Diarrhea
- Dizziness
- Muscle cramps
- Nausea
- Stomach pain
What interactions should I watch for?
Prescription Drugs
Theoretically, creatine may cause kidney damage because its by-product, creatinine, is filtered through the kidneys into urine. If it is taken at the same time as prescription drugs that might also damage kidney tissues, the risk of kidney damage may increase. Classes of prescription drugs that might cause kidney damage include:
- Aminoglycoside antibiotics such as Amikacin, Nebcin, or tobramycin
- Immunosuppressants such as cyclosporine
- Non-steroidal anti-inflammatory drugs such as Advil, Aleve, ibuprofen, Motrin, or naproxen
Non-prescription strengths of non-steroidal anti-inflammatory drugs (NSAIDs) such as Advil, Aleve, ibuprofen, Motrin, naproxen, and many others have a slight risk of causing kidney damage. If creatine, which might also damage the kidneys, is taken at the same time as an NSAID, the risk of kidney damage could increase.
Herbal Products
Ephedra has been removed from the U.S. market. Its use is strongly discouraged. Individuals who take creatine and ephedra at the same time may have an increased risk of side effects. One case of a stroke has been reported in an individual who was taking several dietary supplements that included creatine and ephedra. The exact cause of the stroke is not known, but the combination of creatine and ephedra is best avoided.
Foods
Caffeine appears to cancel the exercise-enhancing effects of creatine when both are used together.
Some interactions between herbal products and medications can be more severe than others. The best way for you to avoid harmful interactions is to tell your doctor and/or pharmacist what medications you are currently taking, including any over-the-counter products, vitamins, and herbals. For specific information on how creatine interacts with drugs, other herbals, and foods and the severity of those interactions, please use our Drug Interactions Checker to check for possible interactions.
Should I take it?
Up to 2,000 mg (2 grams) of creatine are produced each day by the kidneys and liver. Another 1,000 mg to 2,000 mg (one gram to 2 grams) per day comes from the diet -- primarily from meat and fish. Creatine concentrates mostly in the large (skeletal) muscles, where it is involved in producing energy and moderating muscle fatigue. An adult of average weight (about 155 pounds) stores about 120,000 mg (120 grams) of creatine and uses about 2,000 mg (2 grams) every day. However, intensive exercise uses up creatine. It is believed that muscle stores of creatine are decreased dramatically during the first few seconds of exercise. Then, creatine stores gradually replenish over several minutes. As the muscles use energy, creatine is changed into a waste product known as creatinine, which is filtered into the urine by the kidneys. Creatine supplementation may increase the amount of creatine reserve up to 140,000 to 150,000 mg (140 grams to 150 grams), but any excess creatine is lost in the urine.
Supplemental creatine is manufactured artificially by reacting certain chemicals. It is usually sold as citrate, monohydrate, or phosphate salts, which may be easier for the body to use. Although some individuals feel that one salt is more beneficial than the others, no study evidence proves that any one of them works better than the others. Supplemental creatine should be labeled as "100% pure" or "free of impurities", because undesirable byproducts may be produced during manufacturing. Currently, the International Olympic Committee allows Olympic athletes to use creatine while competing in events.
Dosage and Administration
Creatine is available in a number of oral dose forms, with the most reliably consistent being capsules and powders that are usually added to water, low-acid fruit juice (such as apple, grape, pineapple, or tomato juice), or a sports drink that contains carbohydrates. Some research suggests that taking creatine with carbohydrates improves the absorption of creatine. Fruit juices with high acid contents (grapefruit, orange, and other citrus fruit juices) may interfere with the body's absorption of supplemental creatine. One teaspoon of most creatine powders supplies about 5,000 mg (5 grams). Many containers of creatine come with a scoop or spoon that is marked in dosage levels.
Note: Taking commercially-packaged liquid forms of creatine is not recommended due to the likelihood that creatine breaks down in solution.
Dosing for creatine varies depending on the desired effect. One general recommendation for enhancing exercise capability is to take a high dose of creatinine -- 20,000 mg (20 grams or about 4 teaspoons) per day for the first 2 to 7 days and then to reduce the daily dose to 2,000 mg (2 grams). Similar results have been seen with a dose of 3,000 mg (3 grams) every day. Usually, daily amounts of creatine are divided into two doses that are taken 10 to 12 hours apart.
Summary
Creatine is sold mainly to athletes and bodybuilders who want to increase muscle and improve exercise ability. Because it may strengthen muscle, creatine may be useful for degenerative heart and muscle conditions such as muscular dystrophy. Its potential effects on muscle-related diseases and other conditions remain to be proved.
Risks
Creatine is not recommended for individuals with kidney conditions or for children under the age of 18 years old. Pregnant and breast-feeding women are advised to avoid taking it, as well.
Side Effects
Although a definite connection has not been proved, a few individuals have died or experienced kidney collapse while taking creatine. Dehydration is possible and water retention probably will result in weight gain. Less serious side effects may be muscle-related (such as cramps) or gastrointestinal (such as diarrhea or nausea).
Interactions
Theoretically, creatine supplementation may increase the risk of kidney damage is it is taken at the same time as drugs such as certain antibiotics, cyclosporine, or NSAIDs that also may damage kidney tissue. The combination of ephedra and creatine may have adverse effects. Caffeine may cancel or reduce creatine's exercise-enhancing effects.
Last Revised May 26, 2004
References
Andreassen OA, Dedeoglu A, Ferrante RJ, et al. Creatine increase survival and delays motor symptoms in a transgenic animal model of Huntington's disease. Neurobiological Diseases. 2001;8(3):479-491.
Andrews R, Greenhaff P, Curtis S, Perry A, Cowley AJ . The effect of dietary creatine supplementation on skeletal muscle metabolism in congestive heart failure. European Heart Journal 1998;19(4):617-622.
Balsom PD, Soderland K, Ekblom B. Creatine in humans with special reference to creatine supplementation. Sports Medicine. 1994;18(4):268-280.
Balsom PD, Soderlund K, Sjodin B, Ekblom B. Skeletal muscle metabolism during short duration high-intensity exercise: influence of creatine supplementation. Acta Physiologica Scandinavia. 1995;154(3):303-310.
Barnett C, Hinds M, Jenkins DG. Effects of oral creatine supplementation on multiple sprint cycle performance. Australian Journal of Science and Medicine in Sports. 1996;28(1):35-39.
Bergnes G, Yuan W, Khandekar VS, et al. Creatine and phosphocreatine analogs: anticancer activity and enzymatic analysis. Oncology Research. 1996;8(3):121-130.
Bermon S, Venembre P, Sachet C, Valour S, Dolisi C. Effects of creatine monohydrate ingestion in sedentary and weight-trained older adults. Acta Physiologica Scandinavia. 1998;164(2):147-155.
Birch R, Noble D, Greenhaff PL. The influence of dietary creatine supplementation on performance during repeated bouts of maximal isokinetic cycling in man. European Journal of Applied Physiology. 1994;69(3):268-276.
Brose A, Parise G, Tarnopolsky MA. Creatine supplementation enhances isometric strength and body composition improvements following strength exercise training in older adults. Journals of Gerontology. Series A. Biological Sciences and Medical Sciences. 2003 Jan;58(1):11-19.
Brudnak MA. Creatine: are the benefits worth the risk? Toxicology Letters. 2004;150(1):123-130.
Chambers DJ, Haire K, Morley N, et al. St. Thomas' Hospital cardioplegia: enhanced protection with exogenous creatine phosphate. Annals of Thoracic Surgery. 1996;61(1):67-75.
Clarkson PM, Rawson ES. Nutritional supplements to increase muscle mass. Critical Reviews in Food Science and Nutrition. 1999;39(4):317-328.
ConsumerLab. Product review: muscular enhancement supplements: creatine, HM, and glutamine. Initial posting: September 24, 2003. Available at: http://www.consumerlab.com/results/creatine.asp. Accessed December 2, 2003.
Cooke WH, Barnes WS. The influence of recovery duration on high-intensity exercise performance after oral creatine supplementation. Canadian Journal of Applied Physiology. 1997;22(5):454-467.
Cooke WH, Grandjean PW, Barnes WS. Effect of oral creatine supplementation on power output and fatigue during bicycle ergometry. Journal of Applied Physiology. 1995;78(2):670-673.
Dawson B, Cutler M, Moody A, Lawrence S, Goodman C, Randall N. Effects of oral creatine loading on single and repeated maximal short sprints. Australian Journal of Science and Medicine in Sports. 1995;27(3):56-61.
Dedeoglu A, Kubilus JK, Yang L, Ferrante KL, Hersch SM, Beal MF, Ferrante RJ. Creatine therapy provides neuroprotection after onset of clinical symptoms in Huntington's disease transgenic mice. Journal of Neurochemistry. 2003;85(6):1359-1367.
Demant TW, Rhodes EC. Effects of creatine supplementation on exercise performance. Sports Medicine. 1999;28(1):49-60.
Dempsey RL, Mazzone MF, Meurer LN. Does oral creatine supplementation improve strength? A meta-analysis. Journal of Family Practice. 2002;51(11):945-951.
DesJardins M. Supplement use in the adolescent athlete. Current Sports Medicine Report. 2002;1(6):369-373.
Earnest CP, Almada AL, Mitchell TL. High-performance capillary electrophoresis-pure creatine monohydrate reduces blood lipids in men and women. Clinical Sciences. (London) 1996;91(1):113-118.
Farquhar WB, Zambraski EJ. Effects of creatine use on the athlete's kidney. Current Sports Medicine Report. 2002;1(2):103-106.
Febbraio MA, Flanagan TR, Snow RJ, et al. Effect of creatine supplementation on intramuscular TCr, metabolism and performance during intermittent, supramaximal exercise in humans. Acta Physiologica Scandinavia. 1995;155(4):387-395.
Ferraro S, Codella C, Palumbo F, et al. Hemodynamic effects of creatine phosphate in patients with congestive heart failure: a double-blind comparison trial versus placebo. Clinical Cardiology. 1996;19(9):699-703.
Francaux M, Poortmans JR. Effects of training and creatine supplement on muscle strength and body mass. European Journal of Applied Physiology. 1999;80(2):165-168.
Gordon A, Hultman E, Kaijser L, et al. Creatine supplementation in chronic heart failure increases skeletal muscle creatine phosphate and muscle performance. Cardiovascular Research. 1995;30(3):413-418.
Graham AS, Hatton RC. Creatine: a review of efficacy and safety. Journal of the American Pharmaceutical Association. (Washington) 1999;39(6):803-810.
Green AL, Simpson EJ, Littlewood JJ, Macdonald IA, Greenhaff PL. Carbohydrate ingestion augments creatine retention during creatine feeding in humans. Acta Physiologica Scandinavia. 1996;158(2):195-202.
Greenhaff P. Renal dysfunction accompanying oral creatine supplements. Lancet. 1998;352(9123):213-214.
Harris RC, Soderlund K, Hultman E. Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clinical Sciences. (London) 1992;83(3):367-374.
Heinanen K, Nanto-Salonen K, Komu M, et al. Creatine corrects muscle 31P spectrum in gyrate atrophy with hyperornithinaemia. European Journal of Clinical Investigation. 1999;29(12):1060-1065.
Heinanen K, Nanto-Salonen K, Komu M, et al. Muscle creatine phosphate in gyrate atrophy of the choroid and retina with hyperornithinaemia--clues to pathogenesis. European Journal of Clinical Investigation. 1999;29(5):426-431.
Hultman E, Soderlund K, Timmons JA, Cederblad G, Greenhaff PL. Muscle creatine loading in men. Journal of Applied Physiology. 1996;81(1):232-237.
Ingwall JS, Morales MF, Stockdale FE, Wildenthal K. Creatine: a possible stimulus skeletal cardiac muscle hypertrophy. Recent Advances in the Study of Cardiac Structure and Metabolism. 1975;8:467-481.
Jellin JM, Gregory P, Batz F, Hitchens K, et al, eds. Pharmacist's Letter/Prescriber's Letter. Natural Medicines Comprehensive Database, 3rd Edition. Stockton CA: Therapeutic Research Facility, 2000.
Jenkins MA. Creatine supplementation in athletes: review. SportsMed Web. 1998. Available at: http://www.rice.edu/~jenky/sports/creatine.html. Accessed May 26, 2004.
Jones AM, Atter T, Georg KP. Oral creatine supplementation improves multiple sprint performance in elite ice-hockey players. Journal of Sports Medicine and Physical Fitness. 1999;39(3):189-196.
Jowko E, Ostaszewski P, Jank M, et al. Creatine and beta-hydroxy-beta-methylbutyrate (HMB) additively increase lean body mass and muscle strength during a weight-training program. Nutrition. 2001;17(7-8):558-566.
Juhn MS. Oral creatine supplementation. Separating fact from hype. The Physician and Sports Medicine. 1999;27(5):232-234.
Juhn MS, Tarnopolsky M. Potential side effects of oral creatine supplementation: a critical review. Clinical Journal of Sports Medicine. 1998;8(4):298-304.
Kamber M, Koster M, Kreis R, Walker G, Boesch C, Hoppeler H. Creatine supplementation - part I: performance, clinical chemistry, and muscle volume. Medical Science in Sports and Exercise. 1999;31(12):1763-1769.
Kemper KJ. Creatine. The Longwood Herbal Task Force. Revised November 4, 1999. Available at: http://www.mcp.edu/herbal/creatine/creatine.pdf Accessed: December 1, 2003.
Klivenyi P, Calingasan NY, Starkov A, et al. Neuroprotective mechanisms of creatine occur in the absence of mitochondrial creatine kinase. Neurobiology of Disease. 2004;15(3):610-617.
Klivenyi P, Ferrante RJ, Matthews RT, et al. Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis. Nature Medicine. 1999;5(3):347-350.
Kocak S, Karli U. Effects of high dose oral creatine supplementation on anaerobic capacity of elite wrestlers. Journal of Sports Medicine and Physical Fitness. 2003;43(4):488-492.
Kreider RB. Effects of creatine supplementation on performance and training adaptations. Molecular and Cell Biochemistry. 2003;244(1-2):89-94.
Kreider RB, Ferreira M, Wilson M, et al. Effects of creatine supplementation on body composition, strength, and sprint performance. Medical Science in Sports and Exercise. 1998;30(1):73-82.
Kutz MR, Gunter MJ. Creatine monohydrate supplementation on body weight and percent body fat. Journal of Strength and Conditioning Research. 2003;17(4):817-821.
Leenders NM, Lamb DR, Nelson TE. Creatine supplementation and swimming performance. International Journal of Sports Nutrition. 1999;9(3):251-262.
Lillie JW, O'Keefe M, Valinski H, Hamlin HA Jr, Varban ML, Kaddurah-Daouk R. Cyclocreatine (1-carboxymethyl-2-iminoimidazolidine) inhibits growth of a broad spectrum of cancer cells derived from solid tumors. Cancer Research. 1993;53(13):3172-3178.
Lulinski, B. Creatine supplementation. Posted September 17, 1999. http://www.quackwatch.org/01Quackery.../creatine.html. Accessed May 26, 2004.
Martin KJ, Chen SF, Clark GM, et al. Evaluation of creatine analogues as a new class of anticancer agents using freshly explanted human tumor cells. Journal of the National Cancer Institute. 1994;86(8):608-613.
Matthews RT, Ferrante RJ, Klivenyi P, et al. Creatine and cyclocreatine attenuate MPTP neurotoxicity. Experimental Neurology. 1999;157(1):142-149.
Matthews RT, Yang L, Jenkins BG, et al. Neuroprotective effects of creatine and cyclocreatine in animal models of Huntington's disease. Journal of Neuroscience. 1998;18(1):156-163.
Maughan RJ, King DS, Lea T. Dietary supplements. Journal of Sports Science. 2004;22(1):95-113.
MedLine Plus. Dehydration. Updated August 21, 2003. Available at: http://www.nlm.nih.gov/medlineplus/e...cle/000982.htm. Accessed May 26, 2004.
Mendes RR, Tirapegui J. Creatine: the nutritional supplement for exercise - current concepts. [Article in Portuguese] Archivo Latinoamericano Nutrition. 2002;52(2):117-127.
Mihic S, MacDonald JR, McKenzie S, Tarnopolsky MA. Acute creatine loading increases fat-free mass, but does not affect blood pressure, plasma creatinine, or CK activity in men and women. Medical Science in Sports and Exercise. 2000;32(2):291-296.
Miller EE, Evans AE, Cohn M. Inhibition of rate of tumor growth by creatine and cyclocreatine. Proceedings of the National Academy of Sciences (USA). 1993;90:3304-3308.
Mujika I, Chatard J, Lacoste L, Barale F, Geyssant A. Creatine supplementation does not improve sprint performance in competitive swimmers. Medical Science in Sports and Exercise. 1996;28(11):1435-1441.
O'Dea JA. Consumption of nutritional supplements among adolescents: usage and perceived benefits. Health Education Research. 2003;18(1):98-107.
Odland LM, MacDougall JD, Tarnopolsky MA, Elorriaga A, Borgmann A. Effect of oral creatine supplementation on muscle [PCr] and short-term maximum power output. Medical Science in Sports and Exercise. 1997;29(2):216-219.
Palazzetti S, Rousseau AS, Richard MJ, Favier A, Margaritis I. Antioxidant supplementation preserves antioxidant response in physical training and low antioxidant intake. British Journal of Nutrition. 2004;91(1):91-100.
Persky AM, Muller M, Derendorf H, Grant M, Brazeau GA, Hochhaus G. Single- and multiple-dose pharmacokinetics of oral creatine. Journal of Clinical Pharmacology. 2003;43(1):29-37.
Poortmans JR, Auquier H, Renaut V, Durussel A, Saugy M, Brisson GR. Effect of short-term creatine supplementation on renal responses in men. European Journal of Applied Physiology. 1997;76(6):566-567.
Poortmans JR, Francaux M. Adverse effects of creatine supplementation: fact or fiction? Sports Medicine. 2000;30(3):155-170.
Poortmans JR, Francaux M. Long-term oral creatine supplementation does not impair renal function in healthy athletes. Medical Science in Sports and Exercise. 1999;31(8):1108-1110.
Preen D, Dawson B, Goodman C, Lawrence S, Beilby J, Ching S. Effect of creatine loading on long-term sprint exercise performance and metabolism. Medical Science in Sports and Exercise. 2001;33(5):814-821.
Prevost MC, Nelson AG, Morris GS. Creatine supplementation enhances intermittent work performance. Research Quarterly in Exercise and Sports. 1997;68(3):233-240.
Pritchard NR, Kalra PA. Renal dysfunction accompanying oral creatine supplements. Lancet. 1998;351(9111):1252-1253.
Rawson ES, Clarkson PM. Acute creatine supplementation in older men. International Journal of Sports Medicine. 2000;21(1):71-75.
Rawson ES, Volek JS. Effects of creatine supplementation and resistance training on muscle strength and weightlifting performance. Journal of Strength and Conditioning Research. 2003;17(4):822-831.
Rawson ES, Wehnert ML, Clarkson PM. Effects of 30 days of creatine ingestion in older men. European Journal of Applied Physiology. 1999;80(2):139-144.
Rico-Sanz J, Mendez Marco MT. Creatine enhances oxygen uptake and performance during alternating intensity exercise. Medical Science in Sports and Exercise. 2000;32(2):379-385.
Rossiter HB, Cannell ER, Jakeman PM. The effect of oral creatine supplementation on the 1000-m performance of competitive rowers. Journal of Sports Science. 1996;14(2):175-179.
Schilling BK, Stone MH, Utter A, et al. Creatine supplementation and health variables: a retrospective study. Medical Science in Sports and Exercise. 2001;33(2):183-188.
Sipila I, Rapola J, Simell O, Vannas A. Supplementary creatine as a treatment for gyrate atrophy of the choroid and retina. New England Journal of Medicine. 1981;304(15):867-870.
Snow RJ, McKenna MJ, Selig SE, Kemp J, Stathis CG, Zhao S. Effect of creatine supplementation on sprint exercise performance and muscle metabolism. Journal of Applied Physiology. 1998;84(5):1667-1673.
Tarnopolsky MA. Potential benefits of creatine monohydrate supplementation in the elderly. Current Opinion in Clinical Nutrition and Metabolic Care. 2000;3(6):497-502.
Tarnopolsky MA, Beal MF. Potential for creatine and other therapies targeting cellular energy dysfunction in neurological disorders. Annals of Neurology. 2001;49(5):561-574.
Tarnopolsky M, Martin J. Creatine monohydrate increases strength in patients with neuromuscular disease. Neurology. 1999;52(4):854-857.
Tarnopolsky MA, MacLennan DP. Creatine monohydrate supplementation enhances high-intensity exercise performance in males and females. International Journal of Sports Nutrition, Exercise and Metabolism. 2000;10(4):452-463.
Terjung RL, Clarkson P, Eichner ER, et al. The American College of Sports Medicine Roundtable on the physiological and health effects of oral creatine supplementation. Medical Science in Sports and Exercise. 2000;32(3):706-717.
Theodorou AS, Cooke CB, King RF, et al. The effect of longer-term creatine supplementation on elite swimming performance after an acute creatine loading. Journal of Sports Science. 1999;17(11):853-859.
Vahedi K, Domingo V, Amarenco P, Bousser MG. Ischemic stroke in a sportsman who consumed ma huang extract and creatine monohydrate for bodybuilding. Journal of Neurology, Neurosurgery and Psychiatry. 2000;68:112-113.
Vanakoski J, Kosunen V, Meririnne E, Seppala T. Creatine and caffeine in anaerobic and aerobic exercise: effects on physical performance and pharmacokinetic considerations. International Journal of Clinical Pharmacology and Therapeutics. 1998;36(5):258-262.
Vandeberghe K, Gillis N, Van Leemputte M, Van Hecke P, Vanstapel F, Hespel P. Caffeine counteracts the ergogenic action of muscle creatine loading. Journal of Applied Physiology. 1996;80(2):452-457.
Vandeberghe K, Goris M, Van Hecke P, Van Leemputte M, Vangerven L, Hespel P. Long-term creatine intake is beneficial to muscle performance during resistance training. Journal of Applied Physiology. 1997;83(6):2055-2063.
van Loon LJ, Oosterlaar AM, Hartgens F, Hesselink MK, Snow RJ, Wagenmakers AJ. Effects of creatine loading and prolonged creatine supplementation on body composition, fuel selection, sprint and endurance performance in humans. Clinical Sciences. (London). 2003;104(2):153-162.
Vannas-Sulonen K, Sipila I, Vannas A, Simell O, Rapola J. Gyrate atrophy of the choroid and retina. A five-year follow-up of creatine supplementation. Ophthalmology. 1985;92(12):1719-1727.
Volek JS, Ratamess NA, Rubin MR, et al. The effects of creatine supplementation on muscular performance and body composition responses to short-term resistance training overreaching. European Journal of Applied Physiology. Published online December 18, 2003.
Vorgerd M, Grehl T, Jager M, et al. Creatine therapy in myophosphorylase deficiency (McArdle disease): a placebo-controlled crossover trial. Archives of Neurology. 2000;57(7):956-963.
Vorgerd M, Zange J, Kley R, et al. Effect of high-dose creatine therapy on symptoms of exercise intolerance in McArdle disease: double-blind, placebo-controlled crossover study. Archives of Neurology. 2002;59(1):97-101.
Walter MC, Lochmuller H, Reilich P, et al. Creatine monohydrate in muscular dystrophies: A double-blind, placebo-controlled clinical study. Neurology. 2000;54(9):1848-1850.
Williams MH, Branch JD. Creatine supplementation and exercise performance: an update. Journal of the American College of Nutrition. 1998;173):216-234.
Last Revised May 26, 2004
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