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Drugs and Health Products

Creatine Monohydrate

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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 medicinal ingredient.

Notes:

  • 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.

Date

April 12, 2011

Proper name(s)

N-(aminoiminomethyl)-N-methylglycine monohydrate (Merck 2011; US NLM 2011)

Common name(s)

Creatine monohydrate (Merck 2011; US NLM 2011)

Source material(s)

Synthetic (Merck 2011; Weiss and Krommer 1998)

Route(s) of administration

Oral

Dosage form(s)

  • The acceptable pharmaceutical dosage forms include, but are not limited to chewables (e.g. gummies, tablets), caplets, capsules, strips, lozenges, or powders.
    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
Phase Dose (g/day) Duration of use

Footnotes

Footnote 1

References: Okudan and Gokbel 2005; Preen et al. 2003; Bemben et al. 2001; Vandenberghe et al. 1997; Hultman et al. 1996

Return to footnote 1 referrer

Footnote 2

Reference: Hultman et al. 1996

Return to footnote 2 referrer

Footnote 3

References: Preen et al. 2003; Bemben et al. 2001; Volek et al. 1999; Vandenberghe et al. 1997; Hultman et al. 1996

Return to footnote 3 referrer

Loading Phase Option 1Footnote 1 15-20; not to exceed 5 g per dose 5-7 days
Option 2Footnote 2 3-5 Use for a minimum of 4 weeks
Maintenance PhaseFootnote 3 2-5 No statement required

Directions for use: No statement required.

Subpopulation(s)

Adults (≥ 18 years)

Risk information

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).

Contraindication(s):

No statement required.

Known adverse reaction(s):

No statement required.

Non-medicinal ingredients

Must be chosen from the current NNHPD Natural Health Products Ingredients Database and must meet the limitations outlined in the list.

Specifications

  • 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.

References cited

  • 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: Next link will take you to another Web site 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. Next link will take you to another Web site 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. Nutrition 20(7-8):609-614.
  • Weiss S, Krommer H. 1998. Process for the preparation of creatine or creatine monohydrate. U.S. Patent 5,719,319.

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  • 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.
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  • 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 34(4):284-288.
  • 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.
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  • Shao A, Hathcock JN. 2006. Risk assessment for creatine monohydrate. Regulatory Toxicology and Pharmacology 45(3):242-251.
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  • 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 97(7):765-770.
  • 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.
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