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While creatine's influence on physical performance has been well documented since the early twentieth century, it came into public view following the ] in ]. An August 7, 1992 article in '']'' reported that ], the gold medal winner at 100 meters, had used creatine before the Olympics. An article in '']'' named ], who was the gold medalist in the 400-meter hurdles, as another creatine user. In addition, ''The Times'' also noted that 100 meter hurdler ] began taking creatine before the Olympics.<ref>{{cite web|url=http://www.nationalreviewofmedicine.com/issue/2004_07_30/feature07_14.html|title=Supplement muscles in on the market |publisher=National Review of Medicine |date=204-07-30 |accessdate=2011-05-25}}</ref><ref>{{cite book |title=Creatine |last=Passwater |first=Richard A. |year=2005 |publisher= |location= |isbn=0-87983-868-X |page=9 |url=http://books.google.ca/books?id=umy67wOLOckC&printsec=frontcover#v=onepage&q&f=false |accessdate=2011-05-25}}{{page needed|date=May 2012}}</ref> | While creatine's influence on physical performance has been well documented since the early twentieth century, it came into public view following the ] in ]. An August 7, 1992 article in '']'' reported that ], the gold medal winner at 100 meters, had used creatine before the Olympics. An article in '']'' named ], who was the gold medalist in the 400-meter hurdles, as another creatine user. In addition, ''The Times'' also noted that 100 meter hurdler ] began taking creatine before the Olympics.<ref>{{cite web|url=http://www.nationalreviewofmedicine.com/issue/2004_07_30/feature07_14.html|title=Supplement muscles in on the market |publisher=National Review of Medicine |date=204-07-30 |accessdate=2011-05-25}}</ref><ref>{{cite book |title=Creatine |last=Passwater |first=Richard A. |year=2005 |publisher= |location= |isbn=0-87983-868-X |page=9 |url=http://books.google.ca/books?id=umy67wOLOckC&printsec=frontcover#v=onepage&q&f=false |accessdate=2011-05-25}}{{page needed|date=May 2012}}</ref> | ||
At the time, low-potency creatine supplements were available in Britain, but creatine supplements designed for strength enhancement were not commercially available until 1993 when a company called ] (EAS) introduced the compound to the sports nutrition market under the name ''Phosphagen''.<ref>{{Cite book |last= Stoppani |first= Jim |title= Creatine new and improved: recent high-tech advances have made creatine even more powerful. Here's how you can take full advantage of this super supplement |publisher= ] |date= May 2004 |url= http://findarticles.com/p/articles/mi_m0801/is_5_65/ai_n6005938 |accessdate= 2010-03-29}}</ref> Research performed thereafter demonstrated that the consumption of high ] carbohydrates in conjunction with creatine increases creatine muscle stores.<ref>{{cite journal |author=Green AL, Hultman E, Macdonald IA, Sewell DA, Greenhaff PL |title=Carbohydrate ingestion augments skeletal muscle creatine accumulation during creatine supplementation in humans |journal=Am. J. Physiol. |volume=271 |issue=5 Pt 1 |pages=E821–6 |date=November 1996|pmid=8944667 |url= http://ajpendo.physiology.org/cgi/pmidlookup?view=reprint&pmid=8944667}}</ref> In 1998, ] launched Cell-Tech, the first creatine-carbohydrate-alpha lipoic acid supplement.<ref>{{page needed|date=May 2012}}</ref> ] has been demonstrated to enhance muscle phosphocreatine levels and total muscle creatine concentrations. This approach to creatine supplementation was supported by a study performed in 2003.<ref>{{cite journal |pmid=14669930 |year=2003 |last1=Burke |first1=Darren G. |last2=Chilibeck |first2=Philip D. |last3=Parise |first3=Gianni |last4=Tarnopolsky |first4=Mark A. |last5=Candow |first5=Darren G. |title=Effect of α-Lipoic Acid Combined With Creatine Monohydrate on Human Skeletal Muscle Creatine and Phosphagen Concentration |volume=13 |issue=3 |pages=294–302 |journal=International Journal of Sport Nutrition and Exercise Metabolism |url=http://journals.humankinetics.com/ijsnem-back-issues/IJSNEMVolume13Issue3September/EffectofFONTFACESymbolaFONTLipoicAcidCombinedWithCreatineMonohydrateonHumanSkeletalMuscleCreatineandPhosphagenConcentration}}</ref> | At the time, low-potency creatine supplements were available in Britain, but creatine supplements designed for strength enhancement were not commercially available until 1993 when a company called ] (EAS) introduced the compound to the sports nutrition market under the name ''Phosphagen''.<ref>{{Cite book |last= Stoppani |first= Jim |title= Creatine new and improved: recent high-tech advances have made creatine even more powerful. Here's how you can take full advantage of this super supplement |publisher= ] |date= May 2004 |url= http://findarticles.com/p/articles/mi_m0801/is_5_65/ai_n6005938 |accessdate= 2010-03-29}}</ref> Research performed thereafter demonstrated that the consumption of high ] carbohydrates in conjunction with creatine increases creatine muscle stores.<ref>{{cite journal |author=Green AL, Hultman E, Macdonald IA, Sewell DA, Greenhaff PL |title=Carbohydrate ingestion augments skeletal muscle creatine accumulation during creatine supplementation in humans |journal=Am. J. Physiol. |volume=271 |issue=5 Pt 1 |pages=E821–6 |date=November 1996|pmid=8944667 |url= http://ajpendo.physiology.org/cgi/pmidlookup?view=reprint&pmid=8944667|last2=Hultman |last3=MacDonald |last4=Sewell |last5=Greenhaff }}</ref> In 1998, ] launched Cell-Tech, the first creatine-carbohydrate-alpha lipoic acid supplement.<ref>{{page needed|date=May 2012}}</ref> ] has been demonstrated to enhance muscle phosphocreatine levels and total muscle creatine concentrations. This approach to creatine supplementation was supported by a study performed in 2003.<ref>{{cite journal |pmid=14669930 |year=2003 |last1=Burke |first1=Darren G. |last2=Chilibeck |first2=Philip D. |last3=Parise |first3=Gianni |last4=Tarnopolsky |first4=Mark A. |last5=Candow |first5=Darren G. |title=Effect of α-Lipoic Acid Combined With Creatine Monohydrate on Human Skeletal Muscle Creatine and Phosphagen Concentration |volume=13 |issue=3 |pages=294–302 |journal=International Journal of Sport Nutrition and Exercise Metabolism |url=http://journals.humankinetics.com/ijsnem-back-issues/IJSNEMVolume13Issue3September/EffectofFONTFACESymbolaFONTLipoicAcidCombinedWithCreatineMonohydrateonHumanSkeletalMuscleCreatineandPhosphagenConcentration}}</ref> | ||
== Athletic performance == | == Athletic performance == | ||
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Since body mass gains of about 1 kg can occur in a week's time, many studies suggest that the gain is simply due to greater water retention inside the muscle cells.<ref>{{cite journal |pmid=12937471 |year=2003 |last1=Powers |first1=ME |last2=Arnold |first2=BL |last3=Weltman |first3=AL |last4=Perrin |first4=DH |last5=Mistry |first5=D |last6=Kahler |first6=DM |last7=Kraemer |first7=W |last8=Volek |first8=J |title=Creatine Supplementation Increases Total Body Water Without Altering Fluid Distribution |volume=38 |issue=1 |pages=44–50 |pmc=155510 |journal=Journal of athletic training}}</ref> Other studies, however, have shown that creatine increases the activity of ], which make ] possible. Creatine supplementation appears to increase the number of myonuclei that satellite cells will 'donate' to damaged ]s, which increases the potential for growth of those fibers. This increase in myonuclei probably stems from creatine's ability to increase levels of the myogenic transcription factor MRF4.<ref>{{cite journal |pmid=11897886 |year=2001 |last1=Hespel |first1=P |last2=Eijnde |first2=BO |last3=Derave |first3=W |last4=Richter |first4=EA |title=Creatine supplementation: Exploring the role of the creatine kinase/phosphocreatine system in human muscle |volume=26 Suppl |pages=S79–102 |journal=Canadian journal of applied physiology = Revue canadienne de physiologie appliquee |doi=10.1139/h2001-045}}</ref><ref>{{cite journal |doi=10.1113/jphysiol.2006.107359 |title=Creatine supplementation augments the increase in satellite cell and myonuclei number in human skeletal muscle induced by strength training |year=2006 |last1=Olsen |first1=S. |journal=The Journal of Physiology |volume=573 |issue=2 |pmid=16581862 |pages=525–34 |last2=Aagaard |first2=P |last3=Kadi |first3=F |last4=Tufekovic |first4=G |last5=Verney |first5=J |last6=Olesen |first6=JL |last7=Suetta |first7=C |last8=Kjaer |first8=M |pmc=1779717}}</ref> | Since body mass gains of about 1 kg can occur in a week's time, many studies suggest that the gain is simply due to greater water retention inside the muscle cells.<ref>{{cite journal |pmid=12937471 |year=2003 |last1=Powers |first1=ME |last2=Arnold |first2=BL |last3=Weltman |first3=AL |last4=Perrin |first4=DH |last5=Mistry |first5=D |last6=Kahler |first6=DM |last7=Kraemer |first7=W |last8=Volek |first8=J |title=Creatine Supplementation Increases Total Body Water Without Altering Fluid Distribution |volume=38 |issue=1 |pages=44–50 |pmc=155510 |journal=Journal of athletic training}}</ref> Other studies, however, have shown that creatine increases the activity of ], which make ] possible. Creatine supplementation appears to increase the number of myonuclei that satellite cells will 'donate' to damaged ]s, which increases the potential for growth of those fibers. This increase in myonuclei probably stems from creatine's ability to increase levels of the myogenic transcription factor MRF4.<ref>{{cite journal |pmid=11897886 |year=2001 |last1=Hespel |first1=P |last2=Eijnde |first2=BO |last3=Derave |first3=W |last4=Richter |first4=EA |title=Creatine supplementation: Exploring the role of the creatine kinase/phosphocreatine system in human muscle |volume=26 Suppl |pages=S79–102 |journal=Canadian journal of applied physiology = Revue canadienne de physiologie appliquee |doi=10.1139/h2001-045}}</ref><ref>{{cite journal |doi=10.1113/jphysiol.2006.107359 |title=Creatine supplementation augments the increase in satellite cell and myonuclei number in human skeletal muscle induced by strength training |year=2006 |last1=Olsen |first1=S. |journal=The Journal of Physiology |volume=573 |issue=2 |pmid=16581862 |pages=525–34 |last2=Aagaard |first2=P |last3=Kadi |first3=F |last4=Tufekovic |first4=G |last5=Verney |first5=J |last6=Olesen |first6=JL |last7=Suetta |first7=C |last8=Kjaer |first8=M |pmc=1779717}}</ref> | ||
In another study, researchers concluded that changes in substrate oxidation may influence the inhibition of fat mass loss associated with creatine after weight training when they discovered that fat mass did not change significantly with creatine but decreased after the placebo trial in a 12-week study on ten active men. The study also showed that ] bench press and total body mass increased after creatine, but not after placebo.<ref>{{cite journal |first1=M. Erik |last1=Huso |first2=Jeffrey S |last2=Hampl |first3=Carol S. |last3=Johnston |first4=Pamela D. |last4=Swan |journal=Journal of Applied Physiology |pmid=12391059 |url=http://jap.physiology.org/cgi/pmidlookup?view=long&pmid=12391059 |doi=10.1152/japplphysiol.01170.2001 |year=2002 |title=Creatine supplementation influences substrate utilization at rest |volume=93 |issue=6 |pages=2018–22|doi_inactivedate=2014-02-02 }}</ref> The underlying effect of creatine on body composition has yet to be determined, as another study with a similar timeframe suggests no effect on body composition, but had less overall emphasis on metabolic effects.<ref>{{cite journal |doi=10.1139/H07-072 |title=Effect of in-season creatine supplementation on body composition and performance in rugby union football players |year=2007 |last1=Chilibeck |first1=Philip D. |last2=Magnus |first2=Charlene |last3=Anderson |first3=Matthew |journal=Applied Physiology, Nutrition, and Metabolism |volume=32 |issue=6 |pmid=18059577 |pages=1052–7}}</ref> | In another study, researchers concluded that changes in substrate oxidation may influence the inhibition of fat mass loss associated with creatine after weight training when they discovered that fat mass did not change significantly with creatine but decreased after the placebo trial in a 12-week study on ten active men. The study also showed that ] bench press and total body mass increased after creatine, but not after placebo.<ref>{{cite journal |first1=M. Erik |last1=Huso |first2=Jeffrey S |last2=Hampl |first3=Carol S. |last3=Johnston |first4=Pamela D. |last4=Swan |journal=Journal of Applied Physiology |pmid=12391059 |url=http://jap.physiology.org/cgi/pmidlookup?view=long&pmid=12391059 |doi=10.1152/japplphysiol.01170.2001 |year=2002 |title=Creatine supplementation influences substrate utilization at rest |volume=93 |issue=6 |pages=2018–22|doi_inactivedate=2014-02-02 |doi_brokendate=2015-01-11 }}</ref> The underlying effect of creatine on body composition has yet to be determined, as another study with a similar timeframe suggests no effect on body composition, but had less overall emphasis on metabolic effects.<ref>{{cite journal |doi=10.1139/H07-072 |title=Effect of in-season creatine supplementation on body composition and performance in rugby union football players |year=2007 |last1=Chilibeck |first1=Philip D. |last2=Magnus |first2=Charlene |last3=Anderson |first3=Matthew |journal=Applied Physiology, Nutrition, and Metabolism |volume=32 |issue=6 |pmid=18059577 |pages=1052–7}}</ref> | ||
Creatine use is not considered ] and is not banned by the majority of sport-governing bodies. However, in the ], the ] recently ruled that colleges could not provide creatine supplements to their players, though the players are still allowed to obtain and use creatine independently.<ref>{{cite web| title = Creatine | url=http://www.umm.edu/altmed/articles/creatine-000297.htm | publisher = University of Maryland Medical Center | accessdate=8 April 2013}}</ref> | Creatine use is not considered ] and is not banned by the majority of sport-governing bodies. However, in the ], the ] recently ruled that colleges could not provide creatine supplements to their players, though the players are still allowed to obtain and use creatine independently.<ref>{{cite web| title = Creatine | url=http://www.umm.edu/altmed/articles/creatine-000297.htm | publisher = University of Maryland Medical Center | accessdate=8 April 2013}}</ref> | ||
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===Testosterone=== | ===Testosterone=== | ||
A study of male college football players published in 2006 found a 22% increase in resting ] levels, from 20.0 to 24.4 nmol/L, after a 10 week resistance training program in the creatine supplemented group compared to placebo.<ref>{{Cite journal|author=USA |pmid=17136944 |title=Effect of creatine and beta-ala... [Int J Sport Nutr Exerc Metab. 2006] - PubMed - NCBI |publisher=Ncbi.nlm.nih.gov |date=2013-03-25 |volume=16 |issue=4 |journal=Int J Sport Nutr Exerc Metab |pages=430–46}}</ref> | A study of male college football players published in 2006 found a 22% increase in resting ] levels, from 20.0 to 24.4 nmol/L, after a 10 week resistance training program in the creatine supplemented group compared to placebo.<ref>{{Cite journal|author=USA |pmid=17136944 |title=Effect of creatine and beta-ala... [Int J Sport Nutr Exerc Metab. 2006] - PubMed - NCBI |publisher=Ncbi.nlm.nih.gov |date=2013-03-25 |volume=16 |issue=4 |journal=Int J Sport Nutr Exerc Metab |pages=430–46|last2=Ratamess |first2=N |last3=Kang |first3=J |last4=Mangine |first4=G |last5=Faigenbaum |first5=A |last6=Stout |first6=J }}</ref> | ||
===Muscle insulin-like growth factor-I=== | ===Muscle insulin-like growth factor-I=== | ||
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===Buffered creatine=== | ===Buffered creatine=== | ||
Buffered creatine monohydrate (trademarked as Kre-Alkalyn) is claimed to enhance the effects of creatine through the promotion of greater creatine retention and training adaptations with fewer side effects at lower doses (1.5 g/d for 28-days vs. 4 x 5 g/d for 7-days). Research performed found no significant difference in muscle creatine content, body composition, or training adaptations between buffered creatine monohydrate and creatine monohydrate. There was also no evidence that supplementing the diet with a buffered form of creatine resulted in fewer side effects.<ref>{{Cite journal|author= Jagim AR, Oliver JM, Sanchez A, Galvan E, Fluckey J, Riechman S, Greenwood M, Kelly K, Meininger C, Rasmussen C, Kreider RB |pmid=22971354 |title=A buffered form of creatine does not promote greater changes in muscle creatine content, body composition, or training adaptations than creatine monohydrate | journal = J Int Soc Sports Nutr | year = 2012 | volume = 9 | issue = 1 | pages = 43 | doi = 10.1186/1550-2783-9-43 | pmc=3479057}}</ref> | Buffered creatine monohydrate (trademarked as Kre-Alkalyn) is claimed to enhance the effects of creatine through the promotion of greater creatine retention and training adaptations with fewer side effects at lower doses (1.5 g/d for 28-days vs. 4 x 5 g/d for 7-days). Research performed found no significant difference in muscle creatine content, body composition, or training adaptations between buffered creatine monohydrate and creatine monohydrate. There was also no evidence that supplementing the diet with a buffered form of creatine resulted in fewer side effects.<ref>{{Cite journal|author= Jagim AR, Oliver JM, Sanchez A, Galvan E, Fluckey J, Riechman S, Greenwood M, Kelly K, Meininger C, Rasmussen C, Kreider RB |pmid=22971354 |title=A buffered form of creatine does not promote greater changes in muscle creatine content, body composition, or training adaptations than creatine monohydrate | journal = J Int Soc Sports Nutr | year = 2012 | volume = 9 | issue = 1 | pages = 43 | doi = 10.1186/1550-2783-9-43 | pmc=3479057|last2=Oliver |last3=Sanchez |last4=Galvan |last5=Fluckey |last6=Riechman |last7=Greenwood |last8=Kelly |last9=Meininger |last10=Rasmussen |last11=Kreider }}</ref> | ||
===Creatine hydrochloride=== | ===Creatine hydrochloride=== | ||
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===Creatine gluconate=== | ===Creatine gluconate=== | ||
Creatine gluconate is a form of creatine where the molecule is bound to gluconic acid.<ref>{{Cite journal|title=Creatine supplementation with specific view to exercise/sports performance |pmc=3407788 | pmid=22817979 | doi=10.1186/1550-2783-9-33 |volume=9 |issue=1 |year=2012 |journal=J Int Soc Sports Nutr |pages=33}}</ref> | Creatine gluconate is a form of creatine where the molecule is bound to gluconic acid.<ref>{{Cite journal|title=Creatine supplementation with specific view to exercise/sports performance |pmc=3407788 | pmid=22817979 | doi=10.1186/1550-2783-9-33 |volume=9 |issue=1 |year=2012 |journal=J Int Soc Sports Nutr |pages=33|author1=Cooper |first1=R |last2=Naclerio |first2=F |last3=Allgrove |first3=J |last4=Jimenez |first4=A }}</ref> | ||
=== Micronized creatine === | === Micronized creatine === | ||
Since 2011, products containing micronised creatine monohydrate have been marketed as sports supplements. Micronization involves reducing the size of creatine particles to between 0.36 and 9.08 μm in diameter.<ref>{{cite journal|last=Hezave|first=Ali Zeinolabedini|author2=Aftab, Esmaeilzadeh|title=Micronization of creatine monohydrate via Rapid Expansion of Supercritical Solution (RESS)|journal=Journal of Supercritical Fluids|date=November 2010|volume=5|issue=1|pages=316–324 |
Since 2011, products containing micronised creatine monohydrate have been marketed as sports supplements. Micronization involves reducing the size of creatine particles to between 0.36 and 9.08 μm in diameter.<ref>{{cite journal|last=Hezave|first=Ali Zeinolabedini|author2=Aftab, Esmaeilzadeh|title=Micronization of creatine monohydrate via Rapid Expansion of Supercritical Solution (RESS)|journal=Journal of Supercritical Fluids|date=November 2010|volume=5|issue=1|pages=316–324|doi=10.1016/j.supflu.2010.05.009}}</ref> | ||
Purported benefits of these products include easier mixing into drink format for supplementation and faster absorption of the creatine into the bloodstream. While reducing particle size may make powdered creatine easier to dissolve in water due to exposure of a greater total particle surface area to collisions with solvent molecules (increasing the rate of reaction), it cannot change its overall solubility. There is no evidence that micronized creatine monohydrate offers any physiological benefit over other forms or can reduce the risk of gastrointestinal side effects. | Purported benefits of these products include easier mixing into drink format for supplementation and faster absorption of the creatine into the bloodstream. While reducing particle size may make powdered creatine easier to dissolve in water due to exposure of a greater total particle surface area to collisions with solvent molecules (increasing the rate of reaction), it cannot change its overall solubility. There is no evidence that micronized creatine monohydrate offers any physiological benefit over other forms or can reduce the risk of gastrointestinal side effects. | ||
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Current studies indicate that short-term creatine supplementation in healthy individuals is safe, although those with ] should avoid it due to possible risks of renal dysfunction{{citation needed|date=June 2014}}, and before using it healthy users should bear these possible risks in mind. Small-scale, longer-term studies have been done and seem to demonstrate its safety.<ref>{{cite journal |pmid=12500988 |year=2002 |last1=Mayhew |first1=DL |last2=Mayhew |first2=JL |last3=Ware |first3=JS |title=Effects of long-term creatine supplementation on liver and kidney functions in American college football players |volume=12 |issue=4 |pages=453–60 |journal=International journal of sport nutrition and exercise metabolism}}</ref><ref name="Kreider 95–104" /> There have been reports of ] with the use of creatine, though a study showed no reports of muscle cramping in subjects taking creatine on a 15-item panel of qualitative urine markers. Creatine did not cause any clinically significant changes in serum metabolic markers, muscle and liver enzyme efflux, serum electrolytes, blood lipid profiles, red and white whole blood cell hematology, or quantitative and qualitative urinary markers of renal function.<ref name="Kreider 95–104">{{cite journal |doi=10.1023/A:1022469320296 |year=2003 |last1=Kreider |first1=Richard B. |last2=Melton |first2=Charles |last3=Rasmussen |first3=Christopher J. |last4=Greenwood |first4=Michael |last5=Lancaster |first5=Stacy |last6=Cantler |first6=Edward C. |last7=Milnor |first7=Pervis |last8=Almada |first8=Anthony L. |journal=Molecular and Cellular Biochemistry |volume=244 |pages=95–104 |pmid=12701816 |title=Long-term creatine supplementation does not significantly affect clinical markers of health in athletes |issue=1–2}}</ref> | Current studies indicate that short-term creatine supplementation in healthy individuals is safe, although those with ] should avoid it due to possible risks of renal dysfunction{{citation needed|date=June 2014}}, and before using it healthy users should bear these possible risks in mind. Small-scale, longer-term studies have been done and seem to demonstrate its safety.<ref>{{cite journal |pmid=12500988 |year=2002 |last1=Mayhew |first1=DL |last2=Mayhew |first2=JL |last3=Ware |first3=JS |title=Effects of long-term creatine supplementation on liver and kidney functions in American college football players |volume=12 |issue=4 |pages=453–60 |journal=International journal of sport nutrition and exercise metabolism}}</ref><ref name="Kreider 95–104" /> There have been reports of ] with the use of creatine, though a study showed no reports of muscle cramping in subjects taking creatine on a 15-item panel of qualitative urine markers. Creatine did not cause any clinically significant changes in serum metabolic markers, muscle and liver enzyme efflux, serum electrolytes, blood lipid profiles, red and white whole blood cell hematology, or quantitative and qualitative urinary markers of renal function.<ref name="Kreider 95–104">{{cite journal |doi=10.1023/A:1022469320296 |year=2003 |last1=Kreider |first1=Richard B. |last2=Melton |first2=Charles |last3=Rasmussen |first3=Christopher J. |last4=Greenwood |first4=Michael |last5=Lancaster |first5=Stacy |last6=Cantler |first6=Edward C. |last7=Milnor |first7=Pervis |last8=Almada |first8=Anthony L. |journal=Molecular and Cellular Biochemistry |volume=244 |pages=95–104 |pmid=12701816 |title=Long-term creatine supplementation does not significantly affect clinical markers of health in athletes |issue=1–2}}</ref> | ||
In addition, experiments have shown that creatine supplementation improved the health and lifespan of mice.<ref>{{cite journal |doi=10.1016/j.neurobiolaging.2007.03.001 |title=Creatine improves health and survival of mice |year=2008 |last1=Bender |first1=A. |last2=Beckers |first2=J. |last3=Schneider |first3=I. |last4=Hölter |first4=S.M. |last5=Haack |first5=T. |last6=Ruthsatz |first6=T. |last7=Vogt-Weisenhorn |first7=D.M. |last8=Becker |first8=L. |last9=Genius |first9=J. |journal=Neurobiology of Aging |volume=29 |issue=9 |pages=1404–11 |pmid=17416441 }}</ref> Whether these beneficial effects would also apply to humans is still uncertain. | In addition, experiments have shown that creatine supplementation improved the health and lifespan of mice.<ref>{{cite journal |doi=10.1016/j.neurobiolaging.2007.03.001 |title=Creatine improves health and survival of mice |year=2008 |last1=Bender |first1=A. |last2=Beckers |first2=J. |last3=Schneider |first3=I. |last4=Hölter |first4=S.M. |last5=Haack |first5=T. |last6=Ruthsatz |first6=T. |last7=Vogt-Weisenhorn |first7=D.M. |last8=Becker |first8=L. |last9=Genius |first9=J. |last10=Rujescu |first10=D. |last11=Irmler |first11=M. |last12=Mijalski |first12=T. |last13=Mader |first13=M. |last14=Quintanilla-Martinez |first14=L. |last15=Fuchs |first15=H. |last16=Gailus-Durner |first16=V. |last17=De Angelis |first17=M. Hrabé |last18=Wurst |first18=W. |last19=Schmidt |first19=J. |last20=Klopstock |first20=T. |journal=Neurobiology of Aging |volume=29 |issue=9 |pages=1404–11 |pmid=17416441 |display-authors=8 }}</ref> Whether these beneficial effects would also apply to humans is still uncertain. | ||
Creatine supplementation may accelerate the growth of cysts in humans with ]. PKD is prevalent in approximately 1 in 1000 people and may not be detectable until affected individuals reach their thirties.{{citation needed|date=November 2014}} | Creatine supplementation may accelerate the growth of cysts in humans with ]. PKD is prevalent in approximately 1 in 1000 people and may not be detectable until affected individuals reach their thirties.{{citation needed|date=November 2014}} | ||
In 2004 the ] (EFSA) published a record that stated that oral long-term intake of 3 g pure creatine per day is risk-free.<ref>{{cite journal |doi=10.2903/j.efsa.2004.36 |title=Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food on a request from the Commission related to Creatine monohydrate for use in foods for particular nutritional uses Question number EFSA-Q-2003-125 |journal=The EFSA Journal |year=2004 |volume=36 |pages=1–6|doi_inactivedate=2014-02-02 }}</ref> The reports of damage to the kidneys or liver by creatine supplementation have been scientifically refuted.<ref name="Kreider 95–104" /><ref>{{cite journal |doi=10.1007/s00421-007-0669-3 |title=Effects of creatine supplementation on renal function: A randomized, double-blind, placebo-controlled clinical trial |year=2008 |last1=Gualano |first1=Bruno |last2=Ugrinowitsch |first2=Carlos |last3=Novaes |first3=Rafael Batista |last4=Artioli |first4=Guilherme Gianini |last5=Shimizu |first5=Maria Heloisa |last6=Seguro |first6=Antonio Carlos |last7=Harris |first7=Roger Charles |last8=Lancha |first8=Antonio Herbert |journal=European Journal of Applied Physiology |volume=103 |pages=33–40 |pmid=18188581 |issue=1}}</ref><ref>{{cite journal |doi=10.1186/1550-2783-4-6 |title=International Society of Sports Nutrition position stand: Creatine supplementation and exercise |year=2007 |last1=Buford |first1=Thomas W |last2=Kreider |first2=Richard B |last3=Stout |first3=Jeffrey R |last4=Greenwood |first4=Mike |last5=Campbell |first5=Bill |last6=Spano |first6=Marie |last7=Ziegenfuss |first7=Tim |last8=Lopez |first8=Hector |last9=Landis |first9=Jamie |journal=Journal of the International Society of Sports Nutrition |volume=4 |page=6 |pmid=17908288 |pmc=2048496|last10=Antonio |first10=Jose }}</ref><ref>{{cite journal |doi=10.1053/j.ajkd.2009.10.053 |title=Effect of Short-term High-Dose Creatine Supplementation on Measured GFR in a Young Man with a Single Kidney |year=2010 |last1=Gualano |first1=Bruno |last2=Ferreira |first2=Desire Coelho |last3=Sapienza |first3=Marcelo Tatit |last4=Seguro |first4=Antonio Carlos |last5=Lancha |first5=Antonio Herbert |journal=American Journal of Kidney Diseases |volume=55 |issue=3 |pages=e7–9 |pmid=20060630}}</ref> | In 2004 the ] (EFSA) published a record that stated that oral long-term intake of 3 g pure creatine per day is risk-free.<ref>{{cite journal |doi=10.2903/j.efsa.2004.36 |title=Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food on a request from the Commission related to Creatine monohydrate for use in foods for particular nutritional uses Question number EFSA-Q-2003-125 |journal=The EFSA Journal |year=2004 |volume=36 |pages=1–6|doi_inactivedate=2014-02-02 |doi_brokendate=2015-01-11 }}</ref> The reports of damage to the kidneys or liver by creatine supplementation have been scientifically refuted.<ref name="Kreider 95–104" /><ref>{{cite journal |doi=10.1007/s00421-007-0669-3 |title=Effects of creatine supplementation on renal function: A randomized, double-blind, placebo-controlled clinical trial |year=2008 |last1=Gualano |first1=Bruno |last2=Ugrinowitsch |first2=Carlos |last3=Novaes |first3=Rafael Batista |last4=Artioli |first4=Guilherme Gianini |last5=Shimizu |first5=Maria Heloisa |last6=Seguro |first6=Antonio Carlos |last7=Harris |first7=Roger Charles |last8=Lancha |first8=Antonio Herbert |journal=European Journal of Applied Physiology |volume=103 |pages=33–40 |pmid=18188581 |issue=1}}</ref><ref>{{cite journal |doi=10.1186/1550-2783-4-6 |title=International Society of Sports Nutrition position stand: Creatine supplementation and exercise |year=2007 |last1=Buford |first1=Thomas W |last2=Kreider |first2=Richard B |last3=Stout |first3=Jeffrey R |last4=Greenwood |first4=Mike |last5=Campbell |first5=Bill |last6=Spano |first6=Marie |last7=Ziegenfuss |first7=Tim |last8=Lopez |first8=Hector |last9=Landis |first9=Jamie |journal=Journal of the International Society of Sports Nutrition |volume=4 |page=6 |pmid=17908288 |pmc=2048496|last10=Antonio |first10=Jose }}</ref><ref>{{cite journal |doi=10.1053/j.ajkd.2009.10.053 |title=Effect of Short-term High-Dose Creatine Supplementation on Measured GFR in a Young Man with a Single Kidney |year=2010 |last1=Gualano |first1=Bruno |last2=Ferreira |first2=Desire Coelho |last3=Sapienza |first3=Marcelo Tatit |last4=Seguro |first4=Antonio Carlos |last5=Lancha |first5=Antonio Herbert |journal=American Journal of Kidney Diseases |volume=55 |issue=3 |pages=e7–9 |pmid=20060630}}</ref> | ||
==Cognitive performance== | ==Cognitive performance== |
Revision as of 19:09, 11 January 2015
For the biochemistry and physiology of creatine, see Creatine.Creatine supplements are athletic aids used to increase high-intensity athletic performance. Researchers have known of the use of creatine as an energy source by skeletal muscles since the middle of the 20th century. They were popularized as a performance-enhancing supplement beginning in the 1990s.
History
In 1912, Harvard University researchers Otto Folin and Willey Glover Denis found proof that ingesting creatine can dramatically boost the creatine content of the muscle. In the late 1920s, after finding that the intramuscular stores of creatine can be increased by ingesting creatine in larger than normal amounts, scientists discovered creatine phosphate, and determined that creatine is a key player in the metabolism of skeletal muscle. The substance creatine is naturally formed in vertebrates.
While creatine's influence on physical performance has been well documented since the early twentieth century, it came into public view following the 1992 Olympics in Barcelona. An August 7, 1992 article in The Times reported that Linford Christie, the gold medal winner at 100 meters, had used creatine before the Olympics. An article in Bodybuilding Monthly named Sally Gunnell, who was the gold medalist in the 400-meter hurdles, as another creatine user. In addition, The Times also noted that 100 meter hurdler Colin Jackson began taking creatine before the Olympics.
At the time, low-potency creatine supplements were available in Britain, but creatine supplements designed for strength enhancement were not commercially available until 1993 when a company called Experimental and Applied Sciences (EAS) introduced the compound to the sports nutrition market under the name Phosphagen. Research performed thereafter demonstrated that the consumption of high glycemic carbohydrates in conjunction with creatine increases creatine muscle stores. In 1998, MuscleTech Research and Development launched Cell-Tech, the first creatine-carbohydrate-alpha lipoic acid supplement. Alpha lipoic acid has been demonstrated to enhance muscle phosphocreatine levels and total muscle creatine concentrations. This approach to creatine supplementation was supported by a study performed in 2003.
Athletic performance
There is scientific evidence that short term creatine use can increase maximum power and performance in high-intensity anaerobic repetitive work (periods of work and rest) by 5 to 15%. This is mainly bouts of running/cycling sprints and multiple sets of low RM weightlifting. Single effort work shows an increase of 1 to 5%. This refers mainly to single sprints and single lifting of 1-2RM weights. However, some studies show no ergogenic effect at all. Studies in endurance athletes have been less than promising, most likely because these activities are sustained at a given intensity and thus do not allow for significant intra-exercise synthesis of additional creatine phosphate molecules. Ingesting creatine can increase the level of phosphocreatine in the muscles up to 20%. Creatine has no significant effect on aerobic endurance, though it will increase power during short sessions of high-intensity aerobic exercise.
Since body mass gains of about 1 kg can occur in a week's time, many studies suggest that the gain is simply due to greater water retention inside the muscle cells. Other studies, however, have shown that creatine increases the activity of satellite cells, which make muscle hypertrophy possible. Creatine supplementation appears to increase the number of myonuclei that satellite cells will 'donate' to damaged muscle fibers, which increases the potential for growth of those fibers. This increase in myonuclei probably stems from creatine's ability to increase levels of the myogenic transcription factor MRF4.
In another study, researchers concluded that changes in substrate oxidation may influence the inhibition of fat mass loss associated with creatine after weight training when they discovered that fat mass did not change significantly with creatine but decreased after the placebo trial in a 12-week study on ten active men. The study also showed that 1-RM bench press and total body mass increased after creatine, but not after placebo. The underlying effect of creatine on body composition has yet to be determined, as another study with a similar timeframe suggests no effect on body composition, but had less overall emphasis on metabolic effects.
Creatine use is not considered doping and is not banned by the majority of sport-governing bodies. However, in the United States, the NCAA recently ruled that colleges could not provide creatine supplements to their players, though the players are still allowed to obtain and use creatine independently.
Endocrine and other effects
Myostatin levels
In a study from 2010 it was found that 8 weeks of resistance training together with creatine supplementation resulted in lower serum myostatin levels compared to 8 weeks of resistance training and placebo as well as to control (no resistance training or supplementation), ~98 ng/ml, ~110 ng/ml and ~120 ng/ml respectively. In a study from 2011 where broiler chickens were fed creatine for 42 days, myostatin levels were significantly decreased compared to control. Myostatin is a protein that has catabolic effects on skeletal muscle to limit the growth of muscle.
Dihydrotestosterone
A 2009 study examined changes in testosterone levels in college-aged male rugby players receiving Creatine supplementation. Subjects were given a 7 day loading phase of creatine supplementation followed by a further 14 days of creatine maintenance supplementation. While testosterone levels in blood serum were unchanged, levels of dihydrotestosterone increased by 56% after the initial 7 days of creatine loading and remained 40% above baseline after 14 days maintenance. The ratio of dihydrotestosterone to testosterone was therefore increased by 36% after the 7 day creatine supplementation and remained elevated by 22% after the maintenance dose.
Testosterone
A study of male college football players published in 2006 found a 22% increase in resting testosterone levels, from 20.0 to 24.4 nmol/L, after a 10 week resistance training program in the creatine supplemented group compared to placebo.
Muscle insulin-like growth factor-I
One study done in 2008 showed that levels of insulin-like growth factor-1 (IGF-I) in muscle increased by 15% with creatine supplementation compared to placebo after 8 weeks of resistance training. In the same study on broiler chickens mentioned above, IGF-I levels increased compared to control after being fed with creatine for 42 days.
Side effects and drug interactions
Side effects
- Weight gain
- Potential muscle cramps / strains / pulls
- Stomach upset
- Diarrhea
- Dizziness
- High blood pressure
- Liver dysfunction
- Kidney damage
At the recommended dose of being loaded with 20 grams per day for 5 days followed by a maintenance dose of 2 or more grams daily (up to 5 grams), creatine is likely safe and most studies have not found significant side effects. However, people with kidney disease, high blood pressure, or liver disease should not take creatine as a dietary supplement. Being a dietary supplement, it is advised that creatine should be taken under the supervision of a health professional.
Drug interactions
Creatine taken with medications that can harm the kidney can increase the risk of kidney damage. It is advised to speak with your doctor or pharmacist before taking creatine if you are on these type of medications.
- Non-steroidal anti-inflammatory drugs (NSAIDs) - some examples are ibuprofen (Motrin, Advil) and naproxen (Aleve)
- Caffeine - Caffeine and creatine taken together can increase risk of dehydration and cause kidney damage.
- Diuretics (water pills) - An example is furosemide (Lasix)
- Cimetidine (Tagamet)
- Probenicid
Creatine ingestion
Creatine is often taken by many fitness enthusiasts, athletes of all levels, and bodybuilders all around the world to increase performance in anaerobic type activities. There are a number of forms but the most common are creatine monohydrate, (creatine complexed with a molecule of water) and creatine ethyl ester (CEE). A number of methods for ingestion exist: as a powder mixed into a drink, or as a capsule or caplet. Once ingested, creatine is highly bioavailable, whether it is ingested as the crystalline monohydrate form, the free form in solution, or even in meat. Creatine salts will become the free form when dissolved in aqueous solution. Conventional wisdom recommends the consumption of creatine with high glycemic index carbohydrates or a combination of 50% protein and 50% carbohydrate mixture for maximal insulin release and creatine retention.
Endogenous serum or plasma creatine concentrations in healthy adults are normally in a range of 2–12 mg/L. A single 5 g (5000 mg) oral dose in healthy adults results in a peak plasma creatine level of approximately 120 mg/L at 1–2 hours post-ingestion. Creatine has a fairly short elimination half-life, averaging just less than 3 hours, so to maintain an elevated blood plasma level it would be necessary to take small oral doses every 3–6 hours throughout the day. Creatine is consumed by the body fairly quickly, and if one wishes to maintain the high concentration of creatine, 2-5 g daily is the standard amount to intake.
Creatine ethyl ester
Main article: Creatine ethyl esterCEE is a form of commercially available creatine touted to have higher absorption rates and a longer serum half-life than regular creatine monohydrate by several supplement companies. However, no peer-reviewed studies have emerged on creatine ethyl ester which conclusively prove these claims. A study presented at the 4th International Society of Sports Nutrition (ISSN) annual meeting demonstrated that the addition of the ethyl group to creatine actually reduces acid stability and accelerates its breakdown to creatinine. The researchers concluded that creatine ethyl ester is inferior to creatine monohydrate as a source of creatine.
As a supplement, the compound was patented, and licensed through UNeMed, the technology transfer entity of the University of Nebraska Medical Center.
Buffered creatine
Buffered creatine monohydrate (trademarked as Kre-Alkalyn) is claimed to enhance the effects of creatine through the promotion of greater creatine retention and training adaptations with fewer side effects at lower doses (1.5 g/d for 28-days vs. 4 x 5 g/d for 7-days). Research performed found no significant difference in muscle creatine content, body composition, or training adaptations between buffered creatine monohydrate and creatine monohydrate. There was also no evidence that supplementing the diet with a buffered form of creatine resulted in fewer side effects.
Creatine hydrochloride
Creatine hydrochloride (Creatine HCL) is a hydrochloride salt patented in 2009 and marketed as an athletic and bodybuilding supplement. A study by Vireo Systems (commissioned by supplement manufacturer ProMera Health) found creatine hydrochloride to be 59 times more soluble in water than creatine monohydrate. Due to its higher solubility, the recommended dosage for creatine hydrochloride is much lower than that for creatine monohydrate.
Creatine magnesium chelate
Creatine magnesium chelate (pronounced key-late) is a form of creatine bound to two magnesium atoms. Its effects are similar to creatine monohydrate.
Creatine malate
Creatine malate is a creatine compound containing three creatine monohydrate molecules attached to one molecule of malic acid. Creatine monohydrate supports the production of ATP, the muscles primary source of energy in the body. Malic acid plays a supporting role as an intermediate substance that encourages energy transport to the muscles during physical activity, enhancing the Krebs cycle. Because creatine malate combines creatine monohydrate and malic acid into one formula, it can be used to promote lean body mass, muscle strength, explosiveness, endurance, focus, and overall athleticism. Creatine malate is also water-soluble, allowing for fast absorption and meaningful results.
Creatine nitrate
Creatine nitrate is a nitrate salt form of creatine. No benefits have been noted except that it may be more water-soluble.
Creatine gluconate
Creatine gluconate is a form of creatine where the molecule is bound to gluconic acid.
Micronized creatine
Since 2011, products containing micronised creatine monohydrate have been marketed as sports supplements. Micronization involves reducing the size of creatine particles to between 0.36 and 9.08 μm in diameter. Purported benefits of these products include easier mixing into drink format for supplementation and faster absorption of the creatine into the bloodstream. While reducing particle size may make powdered creatine easier to dissolve in water due to exposure of a greater total particle surface area to collisions with solvent molecules (increasing the rate of reaction), it cannot change its overall solubility. There is no evidence that micronized creatine monohydrate offers any physiological benefit over other forms or can reduce the risk of gastrointestinal side effects.
Manufacture
Synthetic creatine is usually made from sarcosine (or its salts) and cyanamide which are combined in a reactor with catalyst compounds. The reactor is heated and pressurized, causing creatine crystals to form. The crystalline creatine is then purified by centrifuge and vacuum dried. The dried creatine compound is milled into a fine powder for improved bioavailability. Milling techniques differ, resulting in final products of varying solubility and bioavailability. For instance, creatine compounds milled to 200 mesh are referred to as micronized.
Safety
Current studies indicate that short-term creatine supplementation in healthy individuals is safe, although those with renal disease should avoid it due to possible risks of renal dysfunction, and before using it healthy users should bear these possible risks in mind. Small-scale, longer-term studies have been done and seem to demonstrate its safety. There have been reports of muscle cramping with the use of creatine, though a study showed no reports of muscle cramping in subjects taking creatine on a 15-item panel of qualitative urine markers. Creatine did not cause any clinically significant changes in serum metabolic markers, muscle and liver enzyme efflux, serum electrolytes, blood lipid profiles, red and white whole blood cell hematology, or quantitative and qualitative urinary markers of renal function.
In addition, experiments have shown that creatine supplementation improved the health and lifespan of mice. Whether these beneficial effects would also apply to humans is still uncertain.
Creatine supplementation may accelerate the growth of cysts in humans with Polycystic Kidney Disease. PKD is prevalent in approximately 1 in 1000 people and may not be detectable until affected individuals reach their thirties.
In 2004 the European Food Safety Authority (EFSA) published a record that stated that oral long-term intake of 3 g pure creatine per day is risk-free. The reports of damage to the kidneys or liver by creatine supplementation have been scientifically refuted.
Cognitive performance
Creatine administration was shown to significantly improve performance in cognitive and memory tests in vegetarian individuals involved in double-blind, placebo-controlled cross-over trials. Vegetarian supplementation with creatine seems to be especially beneficial as they appear to have lower average body stores, since meat is a primary source of dietary creatine. This study did not, however, compare the differing effects of creatine on vegetarians and non-vegetarians. In a later study, a 20g daily dose of creatine monohydrate over 5 days was shown to improve memory in young adult female vegetarians, compared with young adult female omnivores. Note that the vegetarians and non-vegetarians had similar memory scores at the beginning of the study.
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: Unknown parameter|doi_brokendate=
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suggested) (help); Unknown parameter|doi_inactivedate=
ignored (help) - Gualano, Bruno; Ugrinowitsch, Carlos; Novaes, Rafael Batista; Artioli, Guilherme Gianini; Shimizu, Maria Heloisa; Seguro, Antonio Carlos; Harris, Roger Charles; Lancha, Antonio Herbert (2008). "Effects of creatine supplementation on renal function: A randomized, double-blind, placebo-controlled clinical trial". European Journal of Applied Physiology. 103 (1): 33–40. doi:10.1007/s00421-007-0669-3. PMID 18188581.
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{{cite journal}}
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