Hydrolyzed Collagen

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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.

• For the purpose of this monograph, hydrolyzed collagen has no jelling power and is soluble in cold water (Schrieber and Gareis 2007; Moskowitz 2000).The average molecular weight of hydrolyzed collagen is approximately 2-6 kDa (Moskowitz 2000; Oesser et al. 1999).
• 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

Proper name(s)

Hydrolyzed collagen (ChemID 2012; ICIDH 2008)

Common name(s)

• Hydrolyzed collagen (ChemID 2012; ICIDH 2008)
• Collagen hydrosylate (ChemID 2012; ICIDH 2008; Moskowitz 2000)

Source material(s)

• Porcine skin (FCC 7; Baziwane and He 2003)
• Porcine bones (FCC 7; Baziwane and He 2003)
• Fish skin (FCC 7; Baziwane and He 2003)
• Fish bones (FCC 7; Baziwane and He 2003)
• Bovine skin/hide split (FCC 7; Schrieber and Gareis 2007; Baziwane and He 2003)
• Gallus gallus (chicken) cartilage (Schauss et al 2012)

Route(s) of administration

Oral

Dosage form(s)

• The acceptable pharmaceutical dosage forms include, but are not limited to capsules, chewables (e.g. gummies, tablets), liquids, powders, strips or tablets.
• 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

• Source of the essential amino acids histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, valine for the maintenance of good health and involved in protein synthesis (CNF 2010; Eastoe 1955).
• Source of the non-essential amino acids alanine, arginine, aspartic acid, glutamic acid, glycine, proline, serine, tyrosine involved in protein synthesis (CNF 2010; Eastoe 1955).
• Source of the essential amino acid lysine to help in collagen formation (derMarderosian and Beutler 2011; Baziwane and He 2003; Garrison and Somer 1995; Jansen 1962)
• Helps to reduce joint pain associated with osteoarthritis (Bruyère et al. 2012; Benito-Ruiz et al. 2009; Clark et al. 2008).

Dose(s)

Quantity(ies)

Source of the essential amino acids histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, valine:
Minimum 5%^{Quantity footnote1} of each specific amino acid Recommended Dietary Allowance^{Quantity footnote2} to a maximum of 10 g hydrolyzed collagen, per day (JC 2012; Benito-Ruiz et al. 2009; IOM 2005; Moskowitz 2000).

Source of the non-essential amino acid(s) (alanine, arginine, aspartic acid, glutamic acid, glycine, proline, serine, tyrosine):
Minimum 5%^Footnote1 of each specific amino acid Mean Intake^{Quantity footnote3} to a maximum of 10 g hydrolyzed collagen, per day (JC 2012; Benito-Ruiz et al. 2009; IOM 2005; Moskowitz 2000).

Source of lysine:
Minimum 5%^{Quantity footnote 1} of the Recommended Dietary Allowance^{Footnote 2} to a maximum of 10 g hydrolyzed collagen, per day (derMarderosian and Beutler 2011; IOM 2005; Flodin 1997).

Joint pain:
1.2 – 10 g hydrolyzed collagen, per day (Bruyère et al. 2012; Benito-Ruiz et al. 2009; Clark et al. 2008).

Refer to Appendix 2 for examples of dosage preparations. The purpose of Appendix 2 is to provide guidance to industry.

Duration(s) of use

Joint pain:
Use for a minimum of 5 months to see beneficial effects (Bruyère et al. 2012; Benito-Ruiz et al. 2009; Clark et al. 2008).

Risk information

Statement(s) to the effect of

Caution(s) and warning(s)

• If you are pregnant or breastfeeding, consult a health care practitioner prior to use.
• If you have liver or kidney disease or if you have been instructed to follow a low protein diet, consult a health care practitioner prior to use (Shils et al. 2006; Goldman and Ausiello 2004).

Known adverse reaction(s)

May cause mild gastrointestinal disturbances (Moskowitz 2000).

Non-medicinal ingredients

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

Storage conditions

Protect from heat and moisture (Ph.Eur. 2012).

Specifications

• The finished product specifications must be established in accordance with the requirements described in the NNHPD Quality of Natural Health Products Guide.
• The medicinal ingredient must comply with the requirements outlined in the Natural Health Products Ingredients Database (NHPID). In addition the medicinal ingredient may comply with the specifications outlined in the Gelatin Monograph published in the British, European, or United States Pharmacopoeias.

References cited

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• Baziwane D, He Q. Gelatin: The paramount food additive. Food Reviews International 2003;19(4):423-435.
• Benito-Ruiz P, Camacho-Zambrano MM, Carrillo-Arcentales JN, Mestanza-Peralta MA, Vallejo-Flores CA, Vargas-López SV, Villacís-Tamayo RA, Zurita-Gavilanes LA. A randomized controlled trial on the efficacy and safety of a food ingredient, collagen hydrolysate, for improving joint comfort. International Journal of Food Sciences and Nutrition 2009;60 Suppl 2:99-113.
• BP 2012: British Pharmacopoeia 2012. Volume I. London (GB): The Stationary Office on behalf of the Medicines and Healthcare products Regulatory Agency (MHRA); 2012.
• Bruyère O, Zegels B, Leonori L. Rabenda V, Janssen A, Bourges C, Reginster JY. Effect of collagen hydrolysate in articular pain: A 6-month randomized, double-blind, placebo controlled study. Complementary Therapies in Medicine 2012;20:124-130.
• Clark KL, Sebastianelli W, Flechsenhar KR, Aukermann DF, Meza F, Millard RL, Deitch JR, Sherbondy PS, Albert A. 24-Week study on the use of collagen hydrolysate as a dietary supplement in athletes with activity-related joint pain. Current Medical Research and Opinions 2008;24(5):1485-1496.
• CNF 2010: Canadian Nutrient File. Health Canada. [Last modified: 2010 October 21]. [Accessed 2013 May 21].
• derMarderosian A, Beutler JA, editors. The Review of Natural Products. ?Lysine: Issue date February 2011? St Louis (MO): Facts and Comparisons, Wolters Kluwer Health; Printed in 2008 and Updated to June 2011.
• Eastoe JE. The amino acid composition of mammalian collagen and gelatin. Biochemical Journal 1955;61(4):589-600.
• FCC 7: Food Chemical Codex, Seventh Edition. Rockville (MD): The United States Pharmacopeial Convention, 2010.
• Flodin NW. The Metabolic Roles, Pharmacology, and Toxicology of Lysine. Review Article. Journal of the American College of Nutrition 1997;16(1):7-21.
• Garrison RH, Somer E. Nutrition Desk Reference, 3^rd edition. New Canaan (CT): Keats Publishing, 1995.
• Goldman L, Ausiello D, editors. Cecil Textbook of Medicine, Volume 1, 22^nd edition. Philadelphia (PA): Saunders; 2004.
• ICIDH 2008: International Cosmetic Ingredient Dictionary and Handbook, Twelfth Edition, Volume 1. Gottschalck TE, Bailey JE, editors. Washington (DC): The Cosmetic, Toiletry, and Fragrance Association, 2008.
• IOM 2005: Institute of Medicine of the National Academies. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Food and Nutrition Board, [Accessed 2012 May 15].
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• NAS 2005: National Academy of Sciences, Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients), Food and Nutrition Board, [Accessed 2012 May 15].
• Oesser S, Adam M, Babel W, Seifert J. Oral administration of ¹⁴C labeled gelatin hydrolysate leads to an accumulation of radioactivity in cartilage of mice (C57/BL). Journal of Nutrition 129(10):1891-5, 1999.
• Ph.Eur. 2012: European Pharmacopoeia. 7th edition. Strasbourg (FR): Directorate for the Quality of Medicines and HealthCare of the Council of Europe (EDQM); 2012.
• Schauss AG, Stenehjem J, Park J, Endres JR, Clewell A. Effect of the novel low molecular weight hydrolyzed chicken sternal cartilage extract, BioCell Collagen, on improving osteoarthritis-related symptoms: a randomized, double-blind, placebo-controlled trial. J Agric Food Chem. 2012 Apr 25;60(16):4096-101
• Schrieber R, Gareis H. Gelatine Handbook: Theory and Industrial Practice. Weinheim: Wiley-VCH. 2007
• Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ, editors. Modern Nutrition in Health and Disease, 10th edition. Philadelphia (PA): Lippincott Williams and Wilkins, 2006.
• USDA 2002. National Organic Standards Board Technical Advisory Panel Review for the USDA National Organic Program. Gelatin processing. Compiled by Organic Materials Review Institute [Dated: 2002 March 1; Consulted: 2012 May 23].
• USP 35: United States Pharmacopeia and the National Formulary (USP 35 - NF 30). Rockville (MD): The United States Pharmacopeial Convention; 2012.

References reviewed

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• Bello AE, Oesser S. Collagen hydrolysate for the treatment of osteoarthritis and other joint disorders: a review of the literature. Current Medical Research and Opinion 2006;22(11):2221-2232.
• Bornstein P, Sage H. Structurally Distinct Collagen Types. Annual Review of Biochemistry 1980;49:957-1003.
• BP 2008: British Pharmacopoeia Commission. 2007. British Pharmacopoeia 2008. Volume I. London (GB): The Stationary Office on behalf of the Medicines and Healthcare products Regulatory Agency (MHRA).
• ChemID 2012: ChemIDplus advanced. Bethesda (MD): United States National Library of Medicine; 2012. [Hydrolyzed collagen: CAS # 92113-31-0; Accessed 2012 May 22].
• Clark KL, Sebastianelli W, Flechsenhar KR, Aukermann DF, Meza F, Millard RL, Deitch JR, Sherbondy PS, Albert A. 24-Week study on the use of collagen hydrolysate as a dietary supplement in athletes with activity-related joint pain. Current Medical Research and Opinions 2008;24(5):1485-1496.
• Deparle LA, Gupta RC, Canerdy TD, Goad JT, D'Altilio M, Bagchi M, Bagchi D. Efficacy and safety of glycosylated undenatured type-II collagen (UC-II) in therapy of arthritic dogs. Journal of Veterinary Pharmacology and Therapeutics 2005;28(4):385-90.
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Appendix 1 Minimum doses for Amino Acids present in Hydrolyzed Collagen

Appendix 2 Examples of dosage preparations and duration of use for Hydrolyzed Collagen

• 10 g hydrolyzed collagen, per day, for two months (Adam 1991)
• 10 g collagen hydrolysate, per day, for 24 weeks (Moskowitz 2000)
• 10 g hydrolyzed collagen, per day, for 6 months (Benito-Ruiz et al. 2009)