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Drugs and Health Products

Monograph: Krill Oil

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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: (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: 2012-07-04

NHPID Name

Krill oil (ITIS 2007, FAO 2009)

Proper Name(s)

Krill oil ( US FDA 2008 , Bunea et al. 2004 , Takaichi et al. 2003 )

Common Name(s)

Krill oil ( US FDA 2008 , Bunea et al. 2004 , Takaichi et al. 2003 )

Source Material


Oil from whole bodies of Euphausia spp. (Euphausiidae)

Route Of Administration

Oral ( IOM 2002 , Bunea et al. 2004 , Sampalis et al. 2003 )

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:

Dose(s)

Adults:

Dose(s): not to exceed 4.1 Grams per day including at least 100 Milligrams Eicosapentaenoic acid + Docosahexaenoic acid per day

Duration of use

No statement is required

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

Contraindication(s):
No statement is required

Known Adverse Reaction(s):
Hypersensitivity/allergy has been known to occur with shellfish; if this occurs, discontinue use.  (Health Canada 2009)

Non-medicinal ingredients

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

Storage Conditions

  • For all products, except those encapsulated: Refrigerate after opening. (Wille and Gonus 1989)
  • For all products: Store in airtight container, protected from light. (Ph.Eur. 2012 - USP 35)

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).
  • Peroxide, anisidine, and totox values of krill oil or omega-3 fatty acids derived from krill oil must be in accordance with the methods set out by the Association of Analytical Community (AOAC) and/or Pharmacopoeial analytical methods. These specifications are necessary to ensure the oxidative stability of the krill oil and the omega-3 fatty acids from krill oil (HC 2007). The maximum peroxide value (PV) must be 5 mEq/kg, the maximum anisidine value (AV) must be 20 while the maximum Totox value must be 26 (calculated as 2 X PV + AV).
  • The dioxins, polychlorinated dibenzo-para-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs), the dioxin-like polychlorinated biphenyls (DL PCBs), and the polychlorinated biphenyls (PCBs) are contaminants in oils from marine sources. Testing for these contaminants are required, and must be performed using either the analytical method of the European Commission Regulation EU 252/2012 (EU 2012) or the U.S. Environmental Protection Agency's method 1613B for PCDDs and PCDFs and method 1668A for PCBs (USP 35, US EPA 2010, 2008, 1994). Applicants are advised to consult the Council of the European Union document on these contaminants for further information (EU 2011). The maximum limits from EU1259/2011 are: for dioxins (sum of PCDDs and PCDFs) -- a maximum of 1.75 pg/g, for the sum of dioxins and DL PCBs -- a maximum of 6 pg/g, and for PCBs -- a maximum of 200 ng/g. The maximum limits from USP 35 are for dioxins (sum of PCDDs and PCDFs) -- a maximum of 1.0 pg/g, and for PCBs -- a maximum of 0.5 ppm [(i)Maximums levels are expressed in World Health Organization (WHO) toxic equivalents using WHO-toxic equivalent factors (TEFs). Analytical results relating to 17 individual dioxin congeners of toxicological concern are expressed in a single quantifiable unit: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxic equivalent concentration (TEQ) (USP 35, EU 2011) (ii)Reference for sum of dioxins is: WHO-PCDD/F-TEQ (USP 35, EU 2011) (iii) Reference for sum of dioxins and dioxin-like PCBs is: WHO-PCDD/F-PCB-TEQ (EU 2011) (iv) Reference for sum of PCB congeners 28, 52, 101, 118, 138, 153 and 180 is (USP 35, EU 2011) (v) Equivalence: 0.5 ppm = 500ng/g]

References cited

  • Batetta B, Griinari M, Carta G, Murru E, Ligresti A, Cordeddu L, Giordano E, Sanna F, Bisogno T, Uda S, Collu M, Bruheim I, Di Marzo V, Banni S. Endocannabinoids may mediate the ability of (n-3) fatty acids to reduce ectopic fat and inflammatory mediators in obese Zucker rats. J Nutr. 2009 Aug;139(8):1495-501
  • Bunea R, El Farrah K, Deutsch L. Evaluation of the effects of Neptune Krill Oil on the clinical course of hyperlipidemia. Alternative Medicine Review. 2004 9(4):420-428
  • EU 2011: European Commission. Commission Regulation (EU) No 1259/2011 of 2 December 2011 amending Regulation (EC) No 1881/2006 as regards maximum levels for dioxins, dioxin-like PCBs and non dioxin-like PCBs in foodstuffs. Official Journal of the European Union L 320/18 3.12.2011 [Internet]. [Accessed 2012 June 9]. Available from: http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2011:320:0018:0023:EN:PDF
  • EU 2012: European Commission. Commission Regulation (EU) No 252/2012 of 21 March 2012 laying down the methods of sampling and analysis for the official control of levels of dioxins and dioxin-like PCBs and non-dioxin-like PCBs in certain foodstuffs and repealing Regulation (EC) No 1883/2006. Official Journal of the European Union L 84/1 23.3.2012 [Internet]. [Accessed 2012 June 29]. Available from: http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2012:084:0001:0022:EN:PDF
  • HC 2007: Health Canada. 2007. Evidence for Quality of Finished Natural Health Products. Ottawa (ON): Natural Health Products Directorate, Health Canada. Available at: http://www.hc-sc.gc.ca/dhp-mps/prodnatur/legislation/docs/eq-paq-eng.php
  • HC 2009: Health Canada, It's your health. Food Allergies [Internet]. Ottawa (ON): Health Canada. [Original: June 2009; Accessed 2012 March 23] Available from: http://www.hc-sc.gc.ca/hl-vs/alt_formats/pacrb-dgapcr/pdf/iyh-vsv/food-aliment/allerg-eng.pdf
  • IOM 2002: Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Food and Nutrition Board, Institute of Medicine. Washington (DC): National Academy Press; 2002.
  • Ph.Eur. 2012: European Pharmacopoeia, 8th edition. Strasbourg (FR): Directorate for the Quality of Medicines and HealthCare of the Council of Europe (EDQM), 2012.
  • Sampalis F, Bunea R, Pelland MF, Kowalski O, Duguet N, Dupuis S. Evaluation of the effects of Neptune Krill Oil on the management of premenstrual syndrome and dysmenorrhea. Altern Med Rev. 2003 May;8(2):171-9
  • Takaichi S, Matsui K, Nakamura M, Muramatsu M, Hanada S. Fatty acids of astaxanthin esters in krill determined by mild mass spectrometry. Comp Biochem Physiol B Biochem Mol Biol. 2003 Oct;136(2):317-22
  • US EPA 1994: United States Environmental Protection Agency. October 1994. Method 1613, Revision B: Tetra- through Octa-Chlorinated Dioxins and Furans by Isotope Dilution HRGC/HRMS [Internet]. Washington (DC): Engineering and Analysis Division, Office of Water, U.S. Environmental Protection Agency. [Accessed 2012 March 23]. Available from: http://water.epa.gov/scitech/methods/cwa/organics/dioxins/upload/2007_07_10_methods_method_dioxins_1613.pdf
  • US EPA 2008: United States Environmental Protection Agency. November 2008. Method 1668B: Chlorinated Biphenyl Congeners in Water, Soil, Sediment, Biosolids, and Tissue by HRGC/HRMS [Internet]. Washington (DC): Engineering and Analysis Division, Office of Science and Technology, Office of Water, U.S. Environmental Protection Agency. [Accessed 2012 March 23]. Available from: http://water.epa.gov/scitech/methods/cwa/bioindicators/upload/2009_01_07_methods_method_1668.pdf
  • US EPA 2010: United States Environmental Protection Agency. April 2010. Method 1668C: Chlorinated Biphenyl Congeners in Water, Soil, Sediment, Biosolids, and Tissue by HRGC/HRMS [Internet]. Washington (DC): Engineering and Analysis Division, Office of Science and Technology, Office of Water, U.S. Environmental Protection Agency. [Accessed 2012 March 23]. Available from: http://water.epa.gov/scitech/methods/cwa/upload/M1668C_11June10-PCB_Congeners.pdf
  • US FDA 2008. GRAS Notice No GRN 000242. Agency letter GRAS Notice No. GRN 000242. [Internet]. CFSAN/Office of Food Additive Safety. [Accessed 2012 January 30]. Available from: http://www.fda.gov/Food/FoodIngredientsPackaging/GenerallyRecognizedasSafeGRAS/GRASListings/ucm154374.htm
  • USP 35: United States Pharmacopoeial and the National Formulary (USP 35-NF30). Rockville (MD): The United States Pharmacopeial Convention 2012
  • Wille HJ, Gonus P. 1989. Preparation of Fish Oil for Dietary Applications. In: Galli C, Simopolous AP, editors. Dietary omega3 and omega6 Fatty Acids. Biological Effects and Nutritional Essentiality. New York (NY): Plenum Press.

References reviewed

  • Augusti PR, Conterato GM, Somacal S, Sobieski R, Spohr PR, Torres JV, Charão MF, Moro AM, Rocha MP, Garcia SC, Emanuelli T. 2008. Effect of astaxanthin on kidney function impairment and oxidative stress induced by mercuric chloride in rats. Food and Chemical Toxicology 46(1):212-219
  • Calder P C. 2002. Dietary modification of inflammation with lipids. Proceedings of the Nutrition Society 61: 345-358
  • Commission of the European Communities. Commission Regulation (EC) No 1881/2006 of 19 December 2006 setting maximum levels for certain contaminants in foodstuffs. Official Journal of the European Union L 364/5 20.12.2006 [Internet]. [Accessed 2012 March 23]. Available from: http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2006:364:0005:0024:EN:PDF
  • Commission of the European Communities. Commission Regulation (EC) No 1883/2006 of 19 December 2006 laying down the methods of sampling and analysis for the official control of levels of dioxins and dioxin-like PCBs in certain foodstuffs. Official Journal of the European Union L 364/32 20.12.2006 [Internet]. [Accessed 2012 March 23]. Available from: http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2006:364:0032:0043:EN:PDF
  • Grimm H, Mayer K, Mayser P, Eigenbrodt E. 2002. Regulatory potential of n-3 fatty acids in immunological and inflammatory processes. British Journal of Nutrition 87 (suppl): S59-S67
  • Harbige LS. 2003. Fatty Acids, the Immune Response, and Autoimmunity: A Question of n-6 Essentiality and the Balance between n-6 and n-3. Lipids 38: 323-341
  • Higuera-Ciapara I, Félix-Valenzuela L, Goycoolea FM. 2006. Astaxanthin: a review of its chemistry and applications. Critical Reviews in Food Science and Nutrition 46(2):185-96
  • Naguib YM. 2000. Antioxidant activities of astaxanthin and related carotenoids. Journal of Agriculture and Food Chemistry 48(4):1150-1154
  • Simopoulos AP. 1991. Omega-3 fatty acids in health and disease and in growth and development. American Journal of Clinical Nutrition 54: 438-463