The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Clinical Pharmacology of the Dietary Supplement Creatine Monohydrate
Abstract
Creatine is a dietary supplement purported to improve exercise performance and increase fat-free mass. Recent research on creatine has demonstrated positive therapeutic results in various clinical applications. The purpose of this review is to focus on the clinical pharmacology and therapeutic application of creatine supplementation. Creatine is a naturally occurring compound obtained in humans from endogenous production and consumption through the diet. When supplemented with exogenous creatine, intramuscular and cerebral stores of creatine and its phosphorylated form, phosphocreatine, become elevated. The increase of these stores can offer therapeutic benefits by preventing ATP depletion, stimulating protein synthesis or reducing protein degradation, and stabilizing biological membranes. Evidence from the exercise literature has shown athletes benefit from supplementation by increasing muscular force and power, reducing fatigue in repeated bout activities, and increasing muscle mass. These benefits have been applied to disease models of Huntington's, Parkinson's, Duchenne muscular dystrophy, and applied clinically in patients with gyrate atrophy, various neuromuscular disorders, McArdle's disease, and congestive heart failure. This review covers the basics of creatine synthesis and transport, proposed mechanisms of action, pharmacokinetics of exogenous creatine administration, creatine use in disease models, side effects associated with use, and issues on product quality.
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Citations
Cites
Creatine and Creatinine Metabolism
Wyss, M., & Kaddurah-Daouk, R. (2000) · Physiological Reviews · doi:10.1152/physrev.2000.80.3.1107 · Cited by 2,950
Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation
Harris, R. C., Söderlund, K., & Hultman, E. (1992) · Clinical Science · doi:10.1042/cs0830367 · Cited by 1,168 · cited 9×
“However, there does appear to be an upper limit of intramuscular tCr content at ;160 mmol kg(21) of DM (Harris et al., 1992; Casey et al., 1996).”
InfluentialNeuroprotective Effects of Creatine in a Transgenic Mouse Model of Huntington's Disease
Ferrante, R. J., Andreassen, O. A., Jenkins, B. G., Dedeoglu, A., Kuemmerle, S., Kubilus, J. K., Kaddurah-Daouk, R., Hersch, S. M., & Beal, M. F. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-12-04389.2000 · Cited by 522
Long-term creatine intake is beneficial to muscle performance during resistance training
Vandenberghe, K., Goris, M., Van Hecke, P., Van Leemputte, M., Vangerven, L., & Hespel, P. (1997) · Journal of Applied Physiology · doi:10.1152/jappl.1997.83.6.2055 · Cited by 430 · cited 4×
“, 1998) with increases coming from fat-free mass (Vandenberghe et al., 1997; Kreider et al., 1998; Volek et al., 1999; Becque et al., 2000; Mihic et al., 2000).”
InfluentialEffects of creatine supplementation on body composition, strength, and sprint performance
KREIDER, R. B., FERREIRA, M., WILSON, M., GRINDSTAFF, P., PLISK, S., REINARDY, J., CANTLER, E., & ALMADA, A. L. (1998) · Medicine & Science in Sports & Exercise · doi:10.1097/00005768-199801000-00011 · Cited by 430
Creatine deficiency in the brain: A new, treatable inborn error of metabolism
Stöckler, S., Holzbach, U., Hanefeld, F., Marquardt, I., Helms, G., Requart, M., Hänicke, W., & Frahm, J. (1994) · Pediatric Research · doi:10.1203/00006450-199409000-00023 · Cited by 417
Creatine in humans with special reference to creatine supplementation
Balsom, P. D., Söderlund, K., & Ekblom, B. (1994) · Sports Medicine · doi:10.2165/00007256-199418040-00005 · Cited by 404 · cited 1×
“Previous reviews have focused primarily on the improvements in exercise performance seen in human subjects ingesting Cr (Balsom et al., 1994; Mujika and Padilla, 1997; Volek and Kraemer, 1997; Juhn and Tarnopolsky, 1998a; Demant and Rhodes, 1999; Graham and Hatton, 1999; Jacobs, 1999; Kraemer and Volek, 1999; Benzi, 2…”
The creatine kinase system in normal and diseased human myocardium
Ingwall, J. S., Kramer, M. F., Fifer, M. A., Lorell, B. H., Shemin, R., Grossman, W., & Allen, P. D. (1985) · New England Journal of Medicine · doi:10.1056/nejm198510243131704 · Cited by 396
Performance and muscle fiber adaptations to creatine supplementation and heavy resistance training
VOLEK, J. S., DUNCAN, N. D., MAZZETTI, S. A., STARON, R. S., PUTUKIAN, M., G??MEZ, A. L., PEARSON, D. R., FINK, W. J., & KRAEMER, W. J. (1999) · Medicine & Science in Sports & Exercise · doi:10.1097/00005768-199908000-00011 · Cited by 366
Mammalian skeletal muscle fibers distinguished by contents of phosphocreatine, ATP, and Pi
Kushmerick, M. J., Moerland, T. S., & Wiseman, R. W. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.16.7521 · Cited by 301
Brewer, G. J., & Wallimann, T. W. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0741968.x · Cited by 230
Increase of total creatine in human brain after oral supplementation of creatine-monohydrate
Dechent, P., Pouwels, P. J. W., Wilken, B., Hanefeld, F., & Frahm, J. (1999) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1999.277.3.r698 · Cited by 221
Renal dysfunction accompanying oral creatine supplements
Pritchard, N., & Kalra, P. (1998) · The Lancet · doi:10.1016/s0140-6736(05)79319-3 · Cited by 213
Carbohydrate ingestion augments creatine retention during creatine feeding in humans
GREEN, A. L., SIMPSON, E. J., LITTLEWOOD, J. J., MACDONALD, I. A., & GREENHAFF, P. L. (1996) · Acta Physiologica Scandinavica · doi:10.1046/j.1365-201x.1996.528300000.x · Cited by 182
Supplementary creatine as a treatment for gyrate atrophy of the choroid and retina
Sipilä, I., Rapola, J., Simell, O., & Vannas, A. (1981) · New England Journal of Medicine · doi:10.1056/nejm198104093041503 · Cited by 181
Effects of oral creatine supplementation on muscular strength and body composition
BECQUE, M. D., LOCHMANN, J. D., & MELROSE, D. R. (2000) · Medicine & Science in Sports & Exercise · doi:10.1097/00005768-200003000-00016 · Cited by 168
Effects of Creatine Supplementation on Exercise Performance
Demant, T., & Rhodes, E. (1999) · Sports Medicine · doi:10.2165/00007256-199928010-00005 · Cited by 142
Protein- and carbohydrate-induced augmentation of whole body creatine retention in humans
Steenge, G. R., Simpson, E. J., & Greenhaff, P. L. (2000) · Journal of Applied Physiology · doi:10.1152/jappl.2000.89.3.1165 · Cited by 132
Kraemer, W. J., & Volek, J. S. (1999) · Clinics in Sports Medicine · doi:10.1016/s0278-5919(05)70174-5 · Cited by 130
Effects of 30 days of creatine ingestion in older men
Rawson, E. S., Wehnert, M. L., & Clarkson, P. M. (1999) · European Journal of Applied Physiology and Occupational Physiology · doi:10.1007/s004210050570 · Cited by 128
Stimulatory effect of insulin on creatine accumulation in human skeletal muscle
Steenge, G. R., Lambourne, J., Casey, A., Macdonald, I. A., & Greenhaff, P. L. (1998) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1998.275.6.e974 · Cited by 125
Gyrate Atrophy of the Choroid and Retina
Vannas-Sulonen, K., Sipilä, I., Vannas, A., Simell, O., & Rapola, J. (1985) · Ophthalmology · doi:10.1016/s0161-6420(85)34098-8 · Cited by 124
The nutritional biochemistry of creatine
Greenhaff, P. L. (1997) · The Journal of Nutritional Biochemistry · doi:10.1016/s0955-2863(97)00116-2 · Cited by 121
The regulation of total creatine content in a myoblast cell line
Odoom, J., Kemp, G., & Radda, G. (1996) · Molecular and Cellular Biochemistry · doi:10.1007/bf00225844 · Cited by 101
MAGANARIS, C. N., & MAUGHAN, R. J. (1998) · Acta Physiologica Scandinavica · doi:10.1046/j.1365-201x.1998.00395.x · Cited by 98
Earnest, C. P., Almada, A. L., & Mitchell, T. L. (1996) · Clinical Science · doi:10.1042/cs0910113 · Cited by 88
Yu, P. H., & Deng, Y. (2000) · Medical Hypotheses · doi:10.1054/mehy.1999.0938 · Cited by 71 · cited 1×
“It was recently hypothesized that Cr supplementation could be cytotoxic (Yu and Deng, 2000).”
Cited by
The NINDS NET-PD Investigators (2006) · Neurology · doi:10.1212/01.wnl.0000201252.57661.e1 · Cited by 453
Creatine supplementation with specific view to exercise/sports performance: An update
Cooper, R., Naclerio, F., Allgrove, J., & Jimenez, A. (2012) · Journal of the International Society of Sports Nutrition · doi:10.1186/1550-2783-9-33 · Cited by 306
Sestili, P., Martinelli, C., Bravi, G., Piccoli, G., Curci, R., Battistelli, M., Falcieri, E., Agostini, D., Gioacchini, A. M., & Stocchi, V. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2005.10.035 · Cited by 220
Effects of creatine on mental fatigue and cerebral hemoglobin oxygenation
Watanabe, A., Kato, N., & Kato, T. (2002) · Neuroscience Research · doi:10.1016/s0168-0102(02)00007-x · Cited by 196
Helms, E. R., Aragon, A. A., & Fitschen, P. J. (2014) · Journal of the International Society of Sports Nutrition · doi:10.1186/1550-2783-11-20 · Cited by 178
Metadata
- Authors
- Persky, A. M., & Brazeau, G. A.
- Venue
- Pharmacological Reviews
- Publisher
- Elsevier BV
- Published
- 2001-06
- Volume
- 53
- Issue
- 2
- Pages
- 161-176
- ISSN
- 0031-6997 (ISSN-L)
- OpenAlex
- W2154589167
- Cited by
- 332
- References
- 27
- FWCI
- 5.49
- Type
- journal article
- Language
- en
- Open access
- closed
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