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Drugs and Health Products

Monograph: Cranberry

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This monograph is intended to serve as a guide to industry for the preparation of Product Licence Applications (PLA) and labels for natural health product market authorization. It is not intended to be a comprehensive review of the medicinal ingredient. Note: (i) 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. (ii) Claims for traditional use must include the term "Herbal Medicine".

Date: 2011-03-28

NHPID Name

Vaccinium macrocarpon (USDA 2008)

Proper Name(s)

Vaccinium macrocarpon Aiton (Ericaceae) ( USDA 2010 , McGuffin et al 2000 )

Common Name(s)

Source Material

Fruit ( Jepson and Craig 2008 , Mills and Bone 2005 , Stothers 2002 , Upton 2002 , Siciliano 1996 )

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:

Dose(s)

Adults:

Antioxidant
Preparation: Fresh Fruit Equivalents

Dose(s): not to exceed 30 Grams per day, fresh fruit
Preparation: Juice

Dose(s): not to exceed 950 Millilitres per day, fruit juice
Recurrent UTI - traditional; Recurrent UTI - herbal medicine
Preparation: Fresh Fruit Equivalents

Dose(s): 10 - 30 Grams per day, fresh fruit
Preparation: Juice

Dose(s): 90 - 950 Millilitres per day, fruit juice

See Appendix 1 for examples of appropriate dosage preparations and frequencies of use, according to cited references. The purpose of Appendix 1 is to provide guidance to industry.

Duration of use

Recurrent UTI - traditional: Use for a minimum of 4 weeks to see beneficial effects  (Jepson and Craig 2008, Blumenthal et al. 2003, Walker et al. 1997, Avorn et al. 1994)
Recurrent UTI - herbal medicine: Use for a minimum of 4 weeks to see beneficial effects  (Jepson and Craig 2008, Blumenthal et al. 2003, Walker et al. 1997, Avorn et al. 1994)

Risk Information

Statement(s) to the effect of:

Caution(s) and Warning(s):

Contraindication(s):
No statement is required

Known Adverse Reaction(s):
No statement is required

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).
  • Note: Information detailed in this section is not to be submitted with the compendial PLA, although it may be requested at Health Canada's discretion.
  • The medicinal ingredient may comply with the specifications outlined in the Cranberry Liquid Preparation published in the US Pharmacopeia (USP).

References cited

  • Aston JL, Lodolce AE, Shapiro NL. Interaction between warfarin and cranberry juice. Pharmacotherapy 2006;26(9):1314-1319.
  • Avorn J, Monane M, Gurwitz JH, Glynn RJ, Choodnovskiy I, Lipsitz LA. Reduction of bacteriuria and pyuria after ingestion of cranberry juice. Journal of the American Medical Association 1994;271(10):751-754.
  • Barnes J, Anderson LA, Philipson JD. 2007. Herbal Medicines, 3rd edition. London (GB): Pharmaceutical Press.
  • Blumenthal M, Hall T, Goldberg A, Kunz T, Kinda K, editors. 2003. The ABC Clinical Guide to Herbs. Austin (TX): American Botanical Council
  • Bodel PT, Cotron R, Kass EH. 1959. Cranberry juice and the antibacterial action of hippuric acid. The Journal of Laboratory and Clinical Medicine 54(6):881-888.
  • Brinker F. 2010. Final updates and additions for Herb Contraindications and Drug Interactions, 3rd edition. [internet]. Sandy (OR): Eclectic Medical Publications. [Updated 2010 July 13; Accessed 2011 March 28]. Available from: http://www.eclecticherb.com/emp/updateshcdi.html
  • Brinker F. 2010. Final updates and additions for Herb Contraindications and Drug Interactions, 3rd edition. [internet]. Sandy (OR): Eclectic Medical Publications. [Updated 2010 July 13; Accessed 2011 March 7]. Available from: http://www.eclecticherb.com/emp/updateshcdi.html
  • Bruyère F. Utilisation de la canneberge dans les infections urinaires récidivantes. Médecine et maladies infectieuses 2006;36(7):358-363.
  • Gettman MT, Ogan K, Brinkley LJ, Adams-Huet B, Pak CYC, Pearle MS. Effect of cranberry juice consumption on urinary stone risk factors. Journal of Urology 2005;174(2):590-594.
  • Grant P. Warfarin and cranberry juice: an interaction? Journal of Heart Valve Disease 2004;13(1):25-26.
  • Jepson RG, Craig JC. 2008. Cranberries for preventing urinary tract infections. Cochrane Database of Systematic Reviews Issue 3. Art. No.: CD001321. DOI: 10.1002/14651858.CD001321.pub4.
  • McGuffin M, Kartesz JT, Leung AY, Tucker AO, editors. 2000. Herbs of Commerce, 2nd edition. Austin(TX): American Herbal Products Association.
  • McGuffin M, Kartesz JT, Leung AY, Tucker AO, editors. 2000. Herbs of Commerce, 2nd edition. Silver Spring (MD): American Herbal Products Association
  • Mills S, Bone K. 2005. The Essential Guide to Herbal Safety. St. Louis (MO): Elsevier Churchill Livingstone.
  • Rindone JP, Murphy TW. Warfarin-cranberry juice interaction resulting in profound hypoprothrombinemia and bleeding. American Journal of Therapeutics 2005:13(3):283-284.
  • Ruel G, Pomerleau S, Bouture P, Lamarche B, Couillard C. 2005. Changes in plasma antioxidant capacity and oxidized low-density lipoprotein levels in men after short-term cranberry juice consumption. Metabolism Clinical and Experimental 54(7):856-861.
  • Siciliano A. Cranberry. Herbalgram 1996;38:51-54.
  • Stothers L. A randomized trial to evaluate effectiveness and cost effectiveness of naturopathic cranberry products as prophylaxis against urinary tract infection in women. Canadian Journal of Urology 2002;9(3):1558-1562.
  • Terris MK, Issa MM, Tacker JR. Dietary supplementation with cranberry concentrate tablets may increase the risk of nephrolithiasis. Urology 2001;57(1):26-29.
  • Upton R, editor. American Herbal Pharmacopoeia and Therapeutic Compendium: Cranberry Fruit (Vaccinium macrocarpon Aiton) - Standards of Analysis, Quality Control, and Therapeutics. Santa Cruz (CA): American Herbal Pharmacopoeia; 2002.
  • USDA 2010: United States Department of Agriculture, Agricultural Research Service, National Genetic Resources Program. Germplasm Resources Information Network (GRIN) [online database]. Beltsville (MD): National Germplasm Resources Laboratory. [Vaccinium macrocarpon Aiton.: Last updated 2010 January 14; Accessed 2011 March 22]. Available from: http://www.ars-grin.gov/cgi-bin/npgs/html/tax_search.pl.
  • USP 34: United States Pharmacopoeial and the National Formulary (USP 34-NF29). Volume 1 Rockville (MD): The United States Pharmacopeial Convention 2010
  • Valentenova K, Stejskal D, Bednar P, Vostalova J, Cihalik C, Vecerova R, Koukalova D, Kolar M, Reichenbach R, Sknouril L, Ulrichova J, Simanek V. 2007. Biosafety, antioxidant status, and metabolites in urine after consumption of dried cranberry juice in healthy women: a pilot double blind placebo-controlled trial. Journal of Agricultural and Food Chemistry 55(8):3217-3224.
  • Walker EB, Barney DP, Mickelsen JN, Walton RJ, Mickelsen RA. Cranberry concentrate: UTI prophylaxis. Journal of Family Practice 1997;45(2):167-168.
  • Wiersema J, León B. 1999. World Economic Plants: A Standard Reference. Boca Raton (FL): CRC Press LLC.

References reviewed

  • Barnes J, Anderson LA, Philipson JD. 2002. Herbal Medicines: A Guide for Healthcare Professionals, 2nd edition. London (GB): The Pharmaceutical Press.
  • Blatherwick NR, Long ML. 1923. Studies of urinary acidity. II. The increased acidity produced by eating prunes and cranberries. The Journal of Biological Chemistry 57(3):815-818.
  • Boon H, Smith MJ. 2004. The Complete Natural Medicine Guide to the 50 Most Common Medicinal Herbs, 2nd edition. Toronto (ON): Robert Rose Inc.
  • Bristol Myers Squibb. 2005. Coumadin (warfarin) package insert. Princeton (NJ) : Bristol-Myers Squibb [Consulté le 27 février 2009]. Disponible en ligne à : http://www.bms.com/cgi-bin/anybin.pl?sql=select%20PPI%20from%20TB_PRODUCT_PPI%20where%20PPI_SEQ=91&key=PPI
  • Brown DJ. 1996. Herbal Prescriptions for Better Health. Rocklin (CA): Prima Publishing.
  • Chandler F, editor. 2000. Herbs: Everyday Reference for Health Professionals. Ottawa (ON): Canadian Pharmacists Association and the Canadian Medical Association.
  • Di Martino P, Agniel R, David K, Templer C, Gaillard JL, Denys P, Botto H. Reduction of Escherichia coli adherence to uroepithelial bladder cells after consumption of cranberry juice: a double-blind randomized placebo-controlled cross-over trial. World of Urology 2006;24(1):21-27.
  • Fetrow CW, Avila JR. Professional's Handbook of Complementary and Alternative Medicines, 3rd edition. Philadelphia (PA): Lippincott Williams and Wilkins; 2004.
  • Foster S, Tyler VE. Tyler's Honest Herbal: A Sensible Guide to the Use of Herbs and Related Remedies. 4th edition. Binghamton (NY): Haworth Herbal Press; 1999.
  • Gibson L, Pike L, Kilbourn JP. Clinical study: Effectiveness of cranberry juice in preventing urinary tract infections in Long-Term Care Facility patients. Journal of Naturopathic Medicine 1991;2(1):45-47.
  • Gotteland M, Andrews M, Toledo M, Munoz L, Caceres P, Anziani A, Wittig E, Speisky H, Salazar G. 2008. Modulation of Helicobacter pylori colonization with cranberry juice and Lactobacillus johnsonii La1 in children. Nutrition 24(5):421-426.
  • Greenblatt DJ, von Moltke LL von, Perloff ES, Luo Y, Harmatz JS, Zinny MA. 2006. Interaction of flurbiprofen with cranberry juice, grape juice, tea, and fluconazole: In vitro and clinical studies. Clinical Pharmacology and Therapeutics 79(1):125-133.
  • Greenblatt DJ, von Moltke LL. 2006. Interaction of warfarin with drugs, natural substances, and foods. Journal of Clinical Pharmacology 45(2):127-132.
  • Griffiths J, Murty M, Pilon K. 2004. Suspected warfarin-cranberry juice interaction [online]. Ottawa (ON): Health Products and Food Branch, Marketed Health Products Directorate, Health Canada, Canadian Adverse Reaction Newsletter. [Accessed 2009 February 27]. Available from: http://www.hc-sc.gc.ca/dhp-mps/medeff/bulletin/carn-bcei_v14n3_e.html
  • Haverkorn MJ, Mandigers J. 1994. Reduction of bacteriuria and pyuria using cranberry juice [letter]. Journal of the American Medical Association 272(8):590.
  • Henig YS, Leahy MM. 2000. Cranberry juice and urinary tract health: science supports folklore. Nutrition 16(17/18):684-687.
  • Jellin JM, Batz F, Hitchens K, editors. 2003. Pharmacist's Letter/Prescriber's Letter Natural Medicines Comprehensive Database. Stockton (CA): Therapeutic Research Faculty.
  • Jepson RG, Milhaljevic L, Craig J. Cranberries for preventing urinary tract infections (Review). The Cochrane Database of Systematic Reviews, Issue 2. Art. No.: CD001321.pub3. DOI: 10.1002/14651858.CD001321.pub3.; 2004.
  • Lavigne JP, Bourg G, Combescure C, Botto H, Sotto A. 2008. In-vitro and in-vivo evidence of dose-dependant decrease of uropathogenic Escherichia coli virulence after consumption of commercial Vaccinium macrocarpon (cranberry) capsules. Clinical Microbiology and Infection: The Official Publication of the European Society of Clinical Microbiology and Infectious Diseases 14(4):350-355.
  • Lilja JJ, Backman JT, Neuvonen PJ. 2007. Effects of daily ingestion of cranberry juice on the pharmacokinetics of warfarin, tizanidine, and midazolam - probes of CYP2C9, CYP1A2, and CYP3A4. Clinical Pharmacology and Therapeutics 81(6):833-839.
  • McHarg T, Rodgers A, Charlton K. 2001. Influence of cranberry juice on the urinary risk factors for calcium oxalate kidney stone formation. British Journal of Urology 87(4):307-311.
  • McMurdo ME, Bissett LY, Price RJ, Phillips G, Crombie IK. 2005. Does ingestion of cranberry juice reduce symptomatic urinary tract infections in older people in hospital? A double-blind, placebo-controlled trial. Age and Ageing 34(3):256-261.
  • Nowack R. 2007. Cranberry juice - a well-characterized folk-remedy against bacterial urinary tract infection. Wiener Medizinische Wochenschrift 157(13/14):325-330.
  • Pedersen CB, Kyle J, Jenkinson A McE, Gardner PT, McPhail DB, Duthie GG. 2000. Effects of blueberry and cranberry juice consumption on the plasma antioxidant capacity of health female volunteers. European Journal of Clinical Nuttrition 54(5):405-408.
  • Shamseer L, Vohra S. 2007. Complementary, holistic, and integrative medicine: cranberry. Pediatrics in Review/American Academy of Pediatrics 28(8):e43-e45.
  • Shmuely H, Yahav J, Samra Z, Chodick G, Koren R, Niv Y, Ofek I. 2007. Effect of cranberry juice on eradication of Helicobacter pylori in patients treated with antibiotics and a proton pump inhibitor. Molecular Nutrition & Food Research 51(6):746-751.
  • Sobota AE. Inhibition of bacterial adherence by cranberry juice: potential use for the treatment of urinary tract infections. Journal of Urology 1984;131(5):1013-1016.
  • Suvarna R, Pirmohamed M, Henderson L. 2003. Possible interaction between warfarin and cranberry juice. British Medical Journal 327(7429):1454.
  • Vinson JA, Bose P, Proch J, Al Kharrat H, Samman N. 2008. Cranberries and cranberry products: powerful in vitro, ex vivo, and in vivo sources of antioxidants. Journal of Agricultural and Food Chemistry 56(14):5884-5891.
  • Yarnell E. Botanical medicine for cystitis. Alternative Complementary Therapy 1997;269-275.
  • Zhang L, Ma J, Pan K, Go VLW, Chen J, You W. 2005. Efficacy of cranberry juice on Helicobacter pylori infection: a double-blind, randomized placebo-controlled trial. Helicobacter 10(2):139-145.

Appendix 1: Examples of appropriate dosage preparations, frequencies of use and directions for use

Fruit juice preparations equivalent to:

  • 120-950 ml cranberry juice, per day (Blumenthal et al. 2003)
  • 7 ml cranberry juice cocktail per kg body weight, per day (Ruel et al. 2005) (30% cranberry juice)
  • 250 ml cranberry juice, 3 times per day (Stothers et al. 2002)
  • 30-300 ml unsweetened cranberry juice, per day (Upton 2002)
  • 300 ml cranberry juice cocktail, per day (Avorn et al. 1994) (30% cranberry juice)

Other preparations:

  • 200 mg dried cranberry juice, 2 times per day (Valentenova et al. 2007)
  • 400 mg dried cranberry juice, 2 times per day (Valentenova et al. 2007)
  • Preparations equivalent to 10-20 g fresh fruit, per day (Mills and Bone 2005)
  • 400-800 mg dry concentrate (25:1), per day (Mills and Bone 2005)
  • 400 mg cranberry dry extract, 2-3 times per day (Upton 2002)
  • Dry extracts equivalent to 10-30 g fresh fruit (25:1), per day (Upton 2002)
  • 400 mg cranberry concentrate / concentrated cranberry extract, 2 times per day (Walker et al 1997)