Creatine Case Study

Case Study

History

Learning Goals /
Concept Map


Creatine and Related Compounds

Structure

Amino Acids

Creatine in the Body

Equilibrium

Creatine-Creatinine Equilibrium

Creatinine Test for Kidney Function

Detection

Regulation and Ethics

Amine & Nitrile Chemistry

Laboratory Synthesis

Chemical Analysis

Creatine-Phosphocreatine Equilibrium

Uses & Side Effects


Regulation and Ethics

Creatine Supplementation Facts

  • Creatine is considered a food supplement by the Food and Drug Administration (FDA).  As specified by the Dietary Supplement Health and Education Act (DSHEA) of 1994, the FDA’s rules for regulating food supplements are different from those for foods or drugs.  With food supplements, the manufacturer is responsible for establishing safety before marketing, and the FDA takes action if a supplement is found to be unsafe after it has reached the market[1].
  • As such, creatine is not banned by the National Collegiate Athletic Association (NCAA)[2].

NCAA Nutritional/Dietary Supplements Warning[2]

    • “Before consuming any nutritional/dietary supplement product, review the product and its label with your athletics department staff!  “Dietary supplements are not well regulated and may cause a positive drug test result. 
    • “Student-athletes have tested positive and lost their eligibility using dietary supplements.   
    • “Many dietary supplements are contaminated with banned drugs not listed on the label.
    • “Any product containing a dietary supplement ingredient is taken at your own risk.
    • “It is your responsibility to check with athletics staff before using any substance.”
  • Furthermore, creatine is not prohibited by the World Anti-Doping Agency (WADA)[3], which governs the use of drugs in sport, including the Olympics.

Points to Consider

Creatine Supplementation v. Dietary Creatine
Every day, approximately 1.7% of the body’s creatine pool, which is equal to the total amount of creatine and phosphocreatine in the body, is spontaneously and nonenzymatically converted into creatinine.  Therefore, a 155-pound (70 kg) man with 120 grams of creatine loses about 2 grams of creatine each day to creatinine formation.  The lost creatine must be replaced either through the diet or through biosynthesis in the body[4].  Creatine supplementation often involves the ingestion of 20-30 grams of creatine per day for 5 to 6 days.  In order to obtain this much creatine from food sources, a person would need to eat 7 kilograms of meat or fish a day[5].  Contrast this with the 7 ounces of meat and beans a day that the United States Department of Agriculture (USDA) MyPyramid recommends for an active 22-year-old man who is 5’10” and weighs 155 pounds[6].  What do you think about this?  Does creatine supplementation give athletes an unfair advantage?  Why or why not?
 
Creatine v. Caffeine
Like creatine, caffeine occurs naturally in food.  However, caffeine is restricted by the NCAA; if an athlete’s urine contains more than 15 micrograms of caffeine per milliliter of blood, that athlete can be disqualified[2].  Furthermore, until 2004, the International Olympic Committee (IOC) also listed caffeine as a restricted drug, with urinary levels not to exceed 12 milligrams of caffeine per liter of blood[7,8].  The former IOC limit of 12 mg/L could be exceeded with 3-8 cups of coffee a day, depending on the person’s metabolism, medications, and overall health[9,10]

How do the units used by the IOC (mg/L) compare to the units used by the NCAA (ug/mL)?
 
Today, the World Anti-Doping Agency (WADA) does not prohibit caffeine but lists it as one of the substances in its monitoring program[3].  What does this mean?  According to the WADA website, “The World Anti-Doping Code (Article 4.5) states: ‘WADA, in consultation with Signatories and governments, shall establish a monitoring program regarding substances which are not on the Prohibited List, but which WADA wishes to monitor in order to detect patterns of misuse in sport[11].’” Therefore, even though caffeine use is not forbidden for Olympic athletes, the WADA is paying attention to make sure that athletes do not abuse caffeine in competition.  What do you think about this?  Does it make sense for the NCAA to limit the use of caffeine while the WADA merely monitors its use?  What about creatine?  Is there a difference between using caffeine as a performance enhancer and using creatine?
 
Creatine v. Erythropoietin (EPO)
Like creatine, erythropoietin (EPO) is produced endogenously (in the body).  EPO is made in the kidneys and is used in the bone marrow to stimulate the production of red blood cells (RBCs; erythrocytes).  It is used medicinally to treat certain types of anemia; furthermore, some endurance athletes—such as cyclists and cross-country skiers—use EPO to increase the number of RBCs and therefore the oxygen-carrying capacity of their blood.  This is a dangerous practice because more RBCs means thicker blood, and thicker blood can lead to clots.  A blood clot in the brain results in a stroke, and a blood clot in the heart leads to a heart attack[12].  For these reasons—unfair advantage and safety—EPO is banned by both the NCAA[2] and the WADA[3].  What do you think about this?  Does it make sense for the NCAA and WADA to ban an endogenous substance like EPO but not creatine?  Why or why not?
 
Practical Aspects of Testing
Because substances like creatine and erythropoietin are produced by the body, it is challenging to detect whether athletes are supplementing with them.  For example, until recently, doping with EPO had to be determined indirectly by measuring hematocrit levels (that is, the percentage of red blood cells in whole blood).  Today, however, a urine test can distinguish between naturally and synthetically produced EPO[12]
 
Another consideration is that different people produce different amounts of endogenous substances, such as creatine and EPO.  For this reason, even though urine and serum tests for creatine and creatinine are useful, it has been suggested that the only real way to obtain an accurate determination of creatine levels in athletes would be to conduct “serial muscle biopsies over the course of several months[5].”  This process is both invasive and time-consuming.  If creatine were to be banned, how would you resolve the practical issues surrounding detection?

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References

[1]  Dietary Supplements. U. S. Food and Drug Administration, updated 18 Jun 2009. http://www.fda.gov/food/DietarySupplements/default.htm (accessed Dec 2009).
 
[2]  2009-10 NCAA Banned Drugs. The National Collegiate Athletic Association, 10 Jun 2009. http://www.ncaa.org/wps/wcm/connect/53e6f4804e0b8a129949f91ad6fc8b25/2009-10+Banned+Drug+Classes.pdf?MOD=AJPERES&CACHEID=53e6f4804e0b8a129949f91ad6fc8b25 (accessed Dec 2009).
 
[3]  The 2010 Prohibited List, International Standard. The World Anti-Doping Code, in effect 1 Jan 2010. World Anti-Doping Agency. http://www.wada-ama.org/Documents/World_Anti-Doping_Program/WADP-Prohibited-list/WADA_Prohibited_List_2010_EN.pdf (accessed Dec 2009).
 
[4] Wyss, Markus; Kaddurah-Daouk, Rima. “Creatine and Creatinine Metabolism.” Physiol. Rev., 2000, 80(3), 1107-1213.
 
[5]  Williams, Melvin H.; Kreider, Richard B.; Branch, J. David. Creatine: The Power Supplement. Human Kinetics: Champaign, IL, 1999; Ch. 10, pp 217-222.
 
[6]  MyPyramid Plan. United States Department of Agriculture. http://www.mypyramid.gov/mypyramid/index.aspx (accessed Dec 2009).
 
[7] Kennedy, Michael C. “Drugs, Sport and the Olympics 2000–2004.” Med. J. Australia [Online] 2004, 181(4), 227. http://www.mja.com.au/public/issues/181_04_160804/letters_160804_fm-1.html (accessed Dec 2009).
 
[8]  Salleh, Anna. “Athletes’ Caffeine Use Reignites Scientific Debate.” ABC Science Online. http://www.abc.net.au/news/stories/2008/08/02/2322263.htm?site=olympics/2008 (accessed Dec 2009).
 
[9]  Birkett, D. J.; Miners, J. 0. “Caffeine Renal Clearance and Urine Caffeine Concentrations during Steady State Dosing. Implications for Monitoring Caffeine Intake during Sports Events.” Br. J. Clin. Pharmac. [Online] 1991, 31, 405-408. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1368325/pdf/brjclinpharm00059-0037.pdf (accessed Dec 2009).
 
[10] Jenkins, Mark A. “Caffeine and the athlete.” SportsMed Web. Rice University. http://www.rice.edu/~jenky/sports/caffeine.html (accessed Dec 2009).
 
[11]   The 2010 Monitoring Program. The World Anti-Doping Code. World Anti-Doping Agency. http://www.wada-ama.org/Documents/World_Anti-Doping_Program/WADP-Prohibited-list/WADA_Monitoring_Program_2010_EN.pdf (accessed Dec 2009).
 
[12]  Jenkins, Mark A. “Erythropoietin.” SportsMed Web. Rice University. http://www.rice.edu/~jenky/sports/epo.html (accessed Dec 2009).