FRUIT BROMELAIN

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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 and/or statements are synonymous. Either term or statement may be selected by the applicant.

Date

November 25, 2022

Proper name(s), Common name(s), Source information

Table 1. Proper name(s), Common name(s), Source information

Proper name(s)	Common name(s)	Source information
		Source material(s)	Part(s)
Fruit bromelain	Fruit bromelain Juice bromelain Pineapple fruit bromelain	Ananas comosus var. bracteatus Ananas comosus var. comosus	Fruit

References: Proper name: IUBMB 1992; Common names: IUBMB 1992; Source information: USDA 2018.

Route of Administration

Oral

Dosage Form(s)

This monograph excludes foods or food-like dosage forms as indicated in the Compendium of Monographs Guidance Document.

Acceptable dosage forms for oral use are indicated in the dosage form drop-down list of the web-based Product Licence Application form for Compendial applications.

Use(s) or Purpose(s)

• Used in Herbal Medicine to help relieve minor pain, swelling and inflammation (Walker et al. 2002, Blumenthal 1998).
• Digestive enzyme.

Dose(s)

Subpopulation(s)

Adults 18 years and older

Quantity(ies)

Minor pain, swelling and inflammation relief

• 480,000 - 20,000,000 FCC PU of enzymatic activity per day; Not to exceed 10,000,000 FCC PU per single dose (Kerkhoffs et al. 2004; Walker et al. 2002; Glade et al. 2001; Singer et al. 2001; Klein and Kullich 2000; Gutfreund et al. 1978).

Digestive enzyme

• Not to exceed 130,000,000 FCC PU of enzymatic activity per day and 45,000,000 FCC PU per single dose (Kerkhoffs et al. 2004; Walker et al. 2002; Glade et al. 2001; Singer et al. 2001; Klein and Kullich 2000; Gutfreund et al. 1978).

Notes

• Dose information must include the quantities of both the enzyme preparation and its enzymatic activity. The enzymatic activity quantity should be indicated in the Quantity/Unit field and its quantity of enzyme preparation in mg or ml in the Additional Quantity/Unit field.
• 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 microgram of tyrosine per hour under the conditions of the assay (FCC 8 2012).
• One gelatin digestion unit (GDU) is approximately equivalent to 15,000 FCC papain unit (1 GDU≈15,000 FCC PU).

Direction(s) for use

Digestive enzyme (optional for minor pain, swelling and inflammation relief)

Take with food/meal

Duration(s) of Use

Products providing up to 20,000,000 FCC PU of enzymatic activity per day

Consult a health care practitioner/health care provider/health care professional/doctor/physician for prolonged use.

Products providing more than 20,000,000 FCC PU of enzymatic activity per day

For occasional use only.

Risk Information

Caution(s) and warning(s)

• Consult a health care practitioner/health care provider/health care professional/doctor/physician prior to use if you are pregnant or breastfeeding.
• Consult a health care practitioner/health care provider/health care professional/doctor/physician prior to use if you have gastrointestinal lesions/ulcers or are having surgery (Martindale 2011; Brinker 2010; Blumenthal et al. 2000).
• Consult a health care practitioner/health care provider/health care professional/doctor/physician prior to use if you are taking anticoagulant agents, anti-inflammatory agents or antibiotics (Martindale 2011; Brinker 2010; Blumenthal et al. 2000).

Contraindication(s)

No statement required.

Known adverse reaction(s)

• Stop use if hypersensitivity/allergy occurs (Martindale 2011; Brinker 2010; Brien et al. 2006; Murray and Pizzorno 2006; Blumenthal et al. 2000; Baur and Fruhmann 1979).
• Some people may experience gastrointestinal discomfort/disturbances (Martindale 2011; Brinker 2010; Brien et al. 2006; Murray and Pizzorno 2006; Blumenthal et al. 2000; Baur and Fruhmann 1979).

Non-medicinal ingredients

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

Storage conditions

Must be established in accordance with the requirements described in the Natural Health Products Regulations (NHPR).

Specifications

• The finished product specifications must be established in accordance with the requirements described in the Natural and Non-prescription Health Products Directorate (NNHPD) Quality of Natural Health Products Guide.
• The medicinal ingredient must comply with the requirements outlined in the 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. The complete german Commission E monographs: Therapeutic guide to herbal medicines. Boston (MA): American Botanical Council; 1998.
• 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. Herb Contraindications and Drug Interactions, 4^th edition. Sandy (OR): Eclectic Medical Publications; 2010.
• FCC 8 2012: 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 2018 July 23]. 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, randomized, 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 randomized, 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 2018 July 23]. 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 2018: United States Department of Agriculture, Agricultural Research Service, National Genetic Resources Program. Germplasm Resources Information Network (GRIN) [Internet]. Beltsville (MD): National Germplasm Resources Laboratory. [Accessed 2018 July 23]. 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, 15^th edition. Washington (DC): APhA Publications; 2006.
• Repchinsky C, editor-in-chief. Patient Self-Care: Helping Patients Make Therapeutic Choices, 1^st edition. Ottawa (ON): Canadian Pharmacists Association; 2002.