Health Canada
Symbol of the Government of Canada
Drugs and Health Products

Monograph: Bromelain, Fruit

Help on accessing alternative formats, such as Portable Document Format (PDF), Microsoft Word and PowerPoint (PPT) files, can be obtained in the alternate format help section.



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: (i) Text in parentheses is additional optional information which can be included on the PLA and product label at the applicant's discretion. (ii) The solidus (/) indicates that the terms and/or the statements are synonymous. Either term or statement may be selected by the applicant.

Date: 2012-07-05

NHPID Name

Fruit bromelain (IUBMB 2007)

Proper Name(s)

Fruit bromelain ( IUBMB 1992 )

Common Name(s)

Source Material

Ananas comosus var. comosus (Fruit) ( USDA 2011 )

Route 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:

Digestive enzyme  (NHPD 2012)

Dose(s)

Adults:

Dose(s):
not to exceed 600 Milligrams per day of enzyme preparation , not to exceed 300 Milligrams per single dose
 (Kerkhoffs et al. 2004, Walker et al. 2002, Singer et al. 2001, Klein and Kullich 2000, Gutfreund et al. 1978)

Directions For Use: Take with food/meal

Dose(s):
not to exceed 20000000 FCC papain units per day , not to exceed 10000000 FCC papain units per single dose
 (Glade et al. 2001, Gutfreund et al. 1978)

Directions For Use: Take with food/meal


  • Dose unit information must include the quantities of both the enzyme preparation (mg or ml) and its enzymatic activity (FCC or USP units). When submitting by ePLA, please put the enzymatic activity quantity in the Quantity/Unit fields (field 77) and the quantity of enzyme preparation in mg or ml in the Additional Quantity/Unit fields.
  • For multi-ingredient products containing both Papain and Bromelain (fruit and/ or stem), the combined proteolytic activity should not exceed the maximum proteolytic activity of 130 000 000 FCC PU per day.
  • One papain unit (PU) is defined as that quantity of enzyme that liberates the equivalent of 1 g of tyrosine per hour under the conditions of the assay (FCC 8). One gelatin digestion unit (GDU) is approximately equivalent to 15 000 FCC papain unit (1 GDU = approx. 15 000 FCC PU).

Duration of use

For prolonged use, consult a health care practitioner.

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 a gastrointestinal lesion/ ulcer, are taking an anticoagulant/ blood thinner, anti-inflammatory or antibiotic, or are having surgery, consult a health care practitioner prior to use  (Martindale 2011, Brinker 2010, Blumenthal et al. 2000)

Contraindication(s):
No statement is required

Known Adverse Reaction(s):

Non-medicinal ingredients

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

Specifications

  • The finished product specifications must be established in accordance with the requirements described in the NHPD Quality of Natural Health Products Guide.
  • The medicinal ingredient must comply with the requirements outlined in the Natural Health Products Ingredient Database (NHPID).
  • Details of the manufacturing of the enzyme at the raw material stage should include fermentation medium, and the isolation process of the medicinal ingredient.
  • The specifications must include testing for enzymatic activity of the medicinal ingredient at appropriate stages of formulation and manufacturing using the assay outlined in the current Food Chemicals Codex (FCC): PLANT PROTEOLYTIC ACTIVITY.
  • Where published methods are not suitable for use, manufacturers will use due diligence to ensure that the enzymes remain active to the end of the shelf life indicated on the product label.

References cited

  • Baur X, Fruhmann G. Allergic reactions, including asthma, to the pineapple protease bromelain following occupational exposure. Clinical Allergy 1979;9(5):443-450.
  • Blumenthal M, Goldberg A, Brinckmann J, editors. Herbal Medicine: Expanded Commission E Monographs. Boston (MA): Integrative Medicine Communications; 2000.
  • Brien S, Lewith G, Walker AF, Middleton R, Prescott P, Bundy R. Bromelain as an adjunctive treatment for moderate-to-severe osteoarthritis of the knee: a randomized placebo-controlled pilot study. QJM: An International Journal of Medicine 2006;99(12):841-850.
  • Brinker F. Online Updates and Additions to Herb Contraindications and Drug Interactions, 3rd edition [Internet]. Sandy (OR): Eclectic Medical Publications. [Last update July 13, 2010; Accessed 2012 March 28]. Disponible : http://www.eclecticherb.com/emp/updatesHCDI.html
  • FCC 8: Food Chemicals Codex, Eighth edition. Rockville (MD): The United States Pharmacopeial Convention; 2012.
  • Glade MJ, Kendra D, Kaminski MV. Improvement in protein utilization in nursing-home patients on tube feeding supplemented with an enzyme product derived from Aspergillus niger and bromelain. Nutrition 2001;17(4):348-350.
  • Gutfreund AE, Taussig SJ, Morris AD. Effect of oral bromelain on blood pressure and heart rate of hypertensive patients. Hawaii Medical Journal 1978;37(5):143-146.
  • IUBMB 1992: IUBMB Enzyme Nomenclature [Internet]. London (GB): Queen Mary, University of London. [fruit bromelain: CAS 9001-00-7, EC 3.4.22.33 created 1965 as EC 3.4.4.24, transferred 1972 to EC 3.4.22.4, part transferred 1992 to EC 3.4.22.33; Accessed 2012 March 28]. Available from: http://www.chem.qmul.ac.uk/iubmb/enzyme/EC3/4/22/33.html
  • Kerkhoffs GM, Struijs PA, de Wit C, Rahlfs VW, Zwipp H, van Dijk CN. A double blind, randomised, parallel group study on the efficacy and safety of treating acute lateral ankle sprain with oral hydrolytic enzymes. British Journal of Sports Medicine 2004;38;431-435.
  • Klein G, Kullich W. Short-term treatment of painful osteoarthritis of the knee with oral enzymes: a randomised, double-blind study versus diclofenac. Clinical Drug Investigation 2000;19(1):15-23.
  • Martindale 2011: Sweetman SC, editor. Martindale: The Complete Drug Reference [Internet]. London (GB): Pharmaceutical Press; 2012. [Bromelains: syn: EC 3.4.22.33, CAS: 9001-00-7, latest modification 10 Oct 2011; Accessed 2012 March 28]. Available from: http://www.medicinescomplete.com
  • Murray MT, Pizzorno JE. Bromelain. In: Pizzorno JE, Murray MT, editors. Textbook of Natural Medicine, Third edition, volume 1. St. Louis (MI): Churchill Livingstone Elsevier; 2006. p. 791-795.
  • Singer F, Singer C, Oberleitner H. Phlogenzym versus diclofenac in the treatment of activated osteoarthritis of the knee. A double-blind prospective randomized study. International Journal of Immunotherapy XVII 2001;(2/3/4):135-141.
  • USDA 2011: United States Department of Agriculture, Agricultural Research Service, National Genetic Resources Program. Germplasm Resources Information Network (GRIN) [Internet]. Beltsville (MD): National Germplasm Resources Laboratory. [Ananas comosus (L.) Merr. var. comosus (Bromeliaceae): last updated 16-Jun-2011; Accessed 2012 March 28]. Available from: http://www.ars-grin.gov/cgi-bin/npgs/html/tax_search.pl
  • Walker AF, Bundy R, Hicks SM, Middleton RW. Bromelain reduces mild acute knee pain and improves well-being in a dose-dependent fashion in an open study of otherwise health adults. Phytomedicine 2002;9:681-686.

References reviewed

  • Baur X. Studies on the specificity of human IgE-antibodies to the plant proteases papain and bromelain. Clinical & Experimental Allergy 1979;9(5):451-457.
  • Berardi RR, Kroon LA, McDermott JH, Newton GD, Oszko MA, Popovich NG, Remington TL, Rollins CJ, Shimp LA, Tietze KJ, editors. Handbook of Nonprescription Drugs: An Interactive Approach to Self-Care, 15th edition. Washington (DC): APhA Publications; 2006.
  • Repchinsky C, editor-in-chief. Patient Self-Care: Helping Patients Make Therapeutic Choices, 1st edition. Ottawa (ON): Canadian Pharmacists Association; 2002.