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This monograph is intended to serve as a guide to industry for the preparation of
Product Licence Applications (PLAs) and labels for natural health product
market authorization. It is not intended to be a comprehensive review of the
- Text in parentheses is additional optional information which can be included
on the PLA and product label at
the applicant's discretion.
- The solidus (/) indicates that the terms are synonyms
or that the statements are synonymous. Either term or statement may be selected
by the applicant.
April 12, 2011
N-(aminoiminomethyl)-N-methylglycine monohydrate (Merck 2011; US NLM 2011)
Creatine monohydrate (Merck 2011; US NLM 2011)
Synthetic (Merck 2011; Weiss and Krommer 1998)
Route(s) of administration
- The acceptable pharmaceutical dosage forms include, but are not limited
to chewables (e.g. gummies, tablets), caplets, capsules, strips, lozenges, or
Note: Liquids and solutions are not permitted due to
lack of stability of the finished product (Dash and Sawhney 2002).
- This monograph is not intended to include foods or food-like dosage
forms such as bars, chewing gums or beverages.
Use(s) or Purpose(s)
Statement(s) to the effect of:
- Increases [body/muscle/lean] [mass/size] when used in conjunction with a
resistance training regimen (Brose et al. 2003; Bemben et al. 2001; Volek et al. 1999;
Vandenberghe et al. 1997).
- Improves [strength/power/performance] in repetitive bouts of brief, highly-intense
physical activity (e.g. sprints, jumping, resistance training) (by increasing
[muscle/intramuscular] [creatine/phosphocreatine/energy] levels) (Okudan and Gökbel 2005;
Brose et al. 2003; Preen et al. 2003; Bemben et al. 2001; Volek et al. 1999; Vandenberghe
et al. 1997; Hultman et al. 1996).
Dose(s) and Duration of use
Note: Product licence applicants must include both a loading and maintenance
phase dose on the Product Licence Application and product label
Table 1 Dose and duration of use for creatine monohydrate
|15-20; not to exceed 5 g per dose
||Use for a minimum of 4 weeks
||No statement required
Directions for use: No statement required.
Statement(s) to the effect of:
Caution(s) and warning(s):
- Consult a health care practitioner prior to use if you have a kidney disorder
(Pline and Smith 2005; Pritchard and Kalra 1998).
- Consult a health care practitioner prior to use if you are pregnant or breastfeeding.
- May result in weight gain (Volek and Rawson 2004; Bemben et al. 2001; Mihic et al. 2001).
No statement required.
Known adverse reaction(s):
No statement required.
Must be chosen from the current NNHPD Natural Health Products Ingredients Database
and must meet the limitations outlined in the list.
- The finished product must comply with the minimum specifications outlined in the current NNHPD Compendium of Monographs.
- The finished product and/or raw material specifications must have limits for the following impurities: not more than 100
ppm creatinine; not more than 50 ppm dicyandiamide; non-detectable dihydrotriazine. The method used to detect dihydrotriazine
must have a limit of detection of not more than 5 ppm.
Note: The information detailed in this section is not to be submitted with a compendial
PLA, although it may be requested at Health Canada's discretion.
- Bemben MG, Bemben DA, Loftiss DD, Knehans AW. 2001. Creatine supplementation during resistance
training in college football athletes. Medicine & Science in Sports & Exercise 33(10):1667-1673.
- Brose A, Parise G, Tarnopolsky MA. 2003. Creatine supplementation enhances isometric strength and body
composition improvements following strength exercise training in older adults. The Journals of Gerontology
Series A: Biological Science and Medical Science 58(1):11-19.
- Dash AK, Sawhney A. 2002. A simple LC method with
UV detection for the analysis of creatine and creatinine and its application to
several creatine formulations. Journal of Pharmaceutical and Biomedical Analysis 29(5):939-945.
- Hultman E, Söderlund K, Timmons JA, Cederblad G, Greenhaff PL. 1996. Muscle creatine loading in men.
Journal of Applied Physiology 81(l):232-237.
- Merck 2011: The Merck Index Version 14.1. [Internet].
Whitehouse Station (NJ): Merck & Co., Inc. Copyright © 2006, 2011 Merck Sharp & Dohme Corp., a subsidiary
of Merck & Co., Inc. [Accessed 2011 April 8].
- Mihic S, MacDonald JR, McKenzie S, Tarnopolsky MA. 2000. Acute creatine loading increases fat-free mass, but does not
affect blood pressure, plasma creatinine, or CK activity in men and women.
Medicine & Science in Sports and Exercise 32(2):291-296.
- Okudan N, Gökbel H. 2005. The effects of creatine supplementation on performance during the repeated bouts of supramaximal
exercise. Journal of Sports Medicine and Physical Fitness 45(4):507-512.
- Pline KA, Smith CL. 2005. The effect of creatine intake on renal function. The Annals of Pharmacotherapy 39(6):1093-1096.
- Preen D, Dawson B, Goodman C, Beilby J, Ching S. 2003. Creatine supplementation: a comparison of loading and maintenance
protocols on creatine uptake by human skeletal muscle. International Journal of Sport Nutrition and Exercise Metabolism 13(1):97-111.
- Pritchard NR, Kalra PA. 1998. Renal dysfunction accompanying oral creatine supplements. The Lancet 351(9111):1252-1253.
- US NLM 2011: United States National Library of Medicine. ChemIDplus advanced [Internet]. Bethesda (MD): Specialized Information Services,
United States National Library of Medicine, National Institutes of Health, United States Department of Health & Human Services.
[Creatine monohydrate. RN: 6020-87-7. Accessed 2011 April 8].
- Vandenberghe K, Goris M, Van Hecke P, Van Leemputte M, Vangerven L, Hespel P. 1997. Long-term creatine intake is beneficial
to muscle performance during resistance training. Journal of Applied Physiology 83(6):2055-2063.
- Volek JS, Duncan ND, Mazzeti SA, Staron RS, Putukian M, Gomez AL , Pearson DR, Fink WJ, Kraemer WJ. 1999.
Performance and muscle fiber adaptations to creatine supplementation and heavy resistance training. Medicine and Science in
Sports Exercise 31(8):1147-1156.
- Volek JS, Rawson ES. 2004. Scientific basis and practical aspects of creatine supplementation for athletes.
- Weiss S, Krommer H. 1998. Process for the preparation of creatine or creatine monohydrate. U.S. Patent 5,719,319.
- Balsom PD, Söderlund K, Ekblom B. 1994. Creatine in humans with special reference to creatine supplementation.
Sports Medicine 18(4):268-280.
- Bemben MG, Lamont HS. 2005. Creatine supplementation and exercise performance. Sports Medicine 35(2):107-125.
- Bensky D, Gamble A, Kaptchuk T. 1993. Chinese Herbal Medicine Materia Medica. Vista (CA): Eastland Press.
- Benzi G, Ceci A. 2001. Creatine as nutritional supplementation and medicinal product. Journal of Sports Medicine
and Physical Fitness 2001; 41(1):1-10.
- Brudnak MA. 2004. Creatine: are the benefits worth the risk? Toxicology Letters 150(1):123-130.
- Cooke WH, Grandjean PW, Barnes WS. 1995. Effect of oral creatine supplementation on power output and fatigue during
bicycle ergometry. Journal of Applied Physiology 78(2):670-673.
- Cottrell GT, Coast JR, Herb RA. 2002. Effect of recovery interval on multiple-bout sprint cycling performance after
acute creatine supplementation. Journal of Strength and Conditioning Research 16(1):109-116.
- Cox HE. 1936. Composition of meat extracts and meat cubes. Chemistry and Industry 55:69-71.
- Derave W, Eijnde BO, Hespel P. 2003. Creatine supplementation in health and disease: what is the evidence for long-term
efficacy? Molecular and Cellular Biochemistry 244(1-2):49-55.
- Doherty M, Smith PM, Davison RC, Hughes MG. 2002. Caffeine is ergogenic after supplementation of oral creatine monohydrate.
Medicine and Science in Sports and Exercise 34(11):1785-1792.
- Edmunds JW, Jayapalan S, DiMarco NM, Saboorian MH, Aukema HM. 2001. Creatine supplementation increases renal disease progression
in Han:SPRD-cy rats. American Journal of Kidney Diseases 37(1):73-78.
- Emery JA, Henley RR. 1919. Meat extracts, their composition and identification. Journal of Agricultural Research 17(1):1-17.
- Gotshalk LA, Volek JS, Staron RS, Denegar CR, Hagerman FC, Kraemer WJ. 2002. Creatine supplementation improves muscular performance
in older men. Medicine and Science in Sports and Exercise 34(3):537-543.
- Greenwood M, Kreider RB, Melton C, Rasmussen C, Lancaster S, Cantler E, Milnor P, Almada A. 2003. Creatine supplementation during
college football training does not increase the incidence of cramping or injury. Molecular and Cellular Biochemistry 244(1-2):83-88.
- Harris RC, Soderlund K, Hultman E. 1992. Elevation of creatine in resting and exercised muscle of normal subjects by creatine
supplementation. Clinical Science (London) 83(3):367-374.
- HC 2010: Health Canada. MedEffect Canada:
Adverse Reaction Reporting [online]. Ottawa (ON): Canada Vigilance Program, Health Canada. [Accessed 2011 April 12].
- Izquierdo M, Ibanez J, Gonzalez-Badillo J, Gorostiaga EM. 2002. Effects of creatine supplementation on muscle power, endurance,
and sprint performance. Medicine and Science in Sports and Exercise 34(2):332-343.
- Kockler DR, McCarthy MW, Lawson CL. 2001. Seizure activity and unresponsiveness after hydroxycut ingestion. Pharmacotherapy 21(5):647-651.
- Koshy KM, Griswold E, Schneeberger EE. 1999. Interstitial nephritis in a patient taking creatine. The New England Journal
of Medicine 340(10):814-815.
- Kreider RB, Melton C, Rasmussen CJ, Greenwood M, Lancaster S, Cantler EC, Milnor P, Almada AL. 2003. Long-term creatine supplementation
does not significantly affect clinical markers of health in athletes. Molecular and Cellular Biochemistry 244(1-2):95-104.
- McKenna MJ, Morton J, Selig SE, Snow RJ. 1999. Creatine supplementation increases muscle total creatine but not maximal
intermittent exercise performance. Journal of Applied Physiology 87(6):2244-2252
- McRae CA, Agarwal K, Mutimer D, Bassendine MF. 2002. Hepatitis associated with Chinese herbs. European Journal of Gastroenterology
and Hepatology 14(5):559-562.
- Nissen SL and Sharp RL. 2003. Effects of dietary supplements on lean mass and strength gains with resistance exercise: a
meta-analysis. Journal of Applied Physiology 94(2):651-659.
- Ostojic SM, Ahmetovic Z. 2008. Gastrointestinal distress after creatine supplementation in athletes: are side effects dose
dependent? Research in Sports Medicine 16(1):15-22.
- Persky AM, Brazeau GA. 2001. Clinical pharmacology of the dietary supplement creatine monohydrate. Pharmacological Reviews
- Poortmans JR, Auquier H, Renault V, Durussel A, Saugy M, Brisson GR. 1997. Effect of short-term creatine supplementation on
renal responses in men. European Journal of Applied Physiology 76(6):566-567.
- Poortmans JR, Francaux M. 2000. Adverse effects of creatine supplementation: fact or fiction? SportsMedicine 30(3):155-170.
- Poortmans JR, Francaux M. 1999. Long-term oral creatine supplementation does not impair renal function in healthy athletes.
Medicine & Science in Sports & Exercise 31(8):1108-1110.
- Powers ME, Arnold BL, Weltman AL, Perrin DH, Mistry D, Kahler DM, Kraemer W, Volek J. 2003. Creatine supplementation increases
total body water without altering fluid distribution. Journal of Athletic Training 38(1):44-50.
- Prevost MC, Nelson AG, Morris GS. 1997. Creatine supplementation enhances intermittent work performance. Research Quarterly
for Exercise and Sport 68(3):233-240.
- Rawson ES, Clarkson PM, Price TB, Miles MP. 2002. Differential response of muscle phosphocreatine to creatine supplementation
in young and old subjects. Acta Physiologica Scandinavica 174(1):57-65.
- Rico-Sanz J, Mendez MTM. 2000. Creatine enhances oxygen uptake and performance during alternating intensity exercise. Medicine
and Science in Sports and Exercise 32(2):379-385.
- Robinson TM, Sewell DA, Casey A, Steenge G, Greenhaff PL. 2000. Dietary creatine supplementation does not affect some
haematological indices, or indices of muscle damage and hepatic and renal function. British Journal of Sports Medicine
- Saab G, Marsh GD, Casselman MA, Thompson RT. 2002. Changes in human muscle transverse relaxation following short-term
creatine supplementation. Experimental Physiology 87(3):383-389.
- Schilling BK, Stone MH, Utter A, Kearney JT, Johnson M, Coglianese R, Smith L, O'Bryant HS, Fry AC, Starks M, Keith R,
Stone ME. 2001. Creatine supplementation and health variables: a retrospective study. Medicine & Science in Sports &
- Shao A, Hathcock JN. 2006. Risk assessment for creatine monohydrate. Regulatory Toxicology and Pharmacology
- Vahedi K, Domigo V, Amarenco P, Bousser MG. 2000. Ischaemic stroke in a sportsman who consumed MaHuang extract and
creatine monohydrate for body building. Journal of Neurology, Neurosurgery, and Psychiatry 68(1):112-113.
- Volek JK, Kraemer WJ, Bush JA, Boetes M, Incledon T, Clark KL, Lynch JM. 1997. Creatine supplementation enhances
muscular performance during high-intensity resistance exercise. Journal of the American Dietetic Association
- Volek JS, Mazzetti SA, Farquhar WB, Barnes BR, Gómez AL, Kraemer WJ. 2001. Physiological responses to short-term
exercise in the heat after creatine loading. Medicine & Science in Sports & Exercise 33(7):1101-1108.
- Watson G, Casa DJ, Fiala KA, Hile A, Roti MW, Healey JC, Armstrong LE, Maresh CM. 2006. Creatine use and exercise
heat tolerance in dehydrated men. Journal of Athletic Training 41(1):18-29.
- WHO 2008: World Health Organization. World Health Organization Adverse Drug
Reaction database [online]. Uppsala (SE): WHO Collaborating Centre for International Drug Monitoring. [Accessed 24 July 2008].