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Cranberry: Vaccinium macrocarpon Vaccinium oxycoccus.

Common names

Cranberry, American cranberry, bog cranberry, kronsbeere, marsh apple, moosebeere, preisselbeere (Braun 2005, NIH 2005).

Part used

Berries (Braun 2005).

Family

Ericaceae (Foster 1999).

Constituents

Catechin, flavone glycosides, fructose, organic acids, proanthocyanidins, vitamin C, water (80%), carbohydrate 10% (Braun 2005, Raz 2004).

Traditional uses

The medicinal properties of the American cranberry (Vaccinium macrocarpon) have been recognised for centuries. Wound dressings were prepared by the Native Americans by using the whole dried fruit, and also included as part of their food stuff called Pemmican, a combination of crushed berries, fat and dried meat as a meal. The ripe fruit was used medically for treatment of bladder and kidney aliments and removing toxins from the blood (Ulbricht 2005, Lynch 2004, Siciliano 1996).

The value of cranberry was soon learnt by English settlers who healed a variety of ailments including appetite loss, digestive problems, blood disorders and scurvy by using the raw or cooked berries in a sauce for their meats. Relief of liver problems, vomiting and cancer were other documented therapeutic applications of cranberry during the 17th century. Boiled cranberries and seal oil to reduce the severity of gall bladder attacks was adopted by folk medicine practitioners of New England (NIH 2005, ADAM Inc 2004, Siciliano 1996).

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In the 1840s German scientists researched the connection between cranberries and urinary tract infections (UTIs) after noting that urinary excretion of hippuric acid increased after ingestion of cranberries, which are bacteriostatic in high concentrations (Hutchinson 2005, Ulbricht 2005, Siciliano 1996).

Major medicinal uses

Current evidence has built on earlier research relating to the ability of cranberries to assist urinary tract infections. It is now understood that the mechanism of action of cranberries does not lie in acidification of urine, rather it works by inhibiting adhesion of the bacteria E. coli to uroepithelial cells in the bladder.

A 75% anti-adhesion rate for 66 to 77 E. coli clinically isolated, uroepithelial cells, was demonstrated in one of the initial in vitro trials (Soboto 1984). On the bacterial cell wall there exist hairlike fimbriae or pili, which produce adhesions to attract themselves to specific receptors on the urinary bladder.

Cranberry juice contains two constituents, fructose and a group of compounds called proanthocyanidins (condensed tannins) that prevent attachment to the uropathogenic type 1 and Pfimbriated strains of E. coli that would otherwise result in the development of urinary tract infection (Hutchinson 2005, Ulbricht 2005, Dorren 2005, Howell 2002).

A recent open randomised control trial involving 150 women who had UTIs resulting from Escherichia coli, saw a risk reduction rate of 20% in the cranberry group, compared with the control group. Group one consumed 50 mL of cranberry-lingonberry juice concentrate daily; group 2 ingested 100 mL of lactobacillus drink; in the third group no intervention treatment was allocated. One reoccurrence of infection after 6 months of treatment was seen in 16% of cranberry group, 39% of the lactobacillus group and 36% of the control group (Kontiokari 2001).

Another randomised placebo controlled double blind study (Stothers 2002) involving 150 women with urinary tract infections supported the positive results of Kontiokari et al (2001) for the use of cranberry. After 1 year 32% of the placebo group, compared with 20% of the cranberry juice group and 18% of the cranberry tablet group, experienced UIT reoccurrence. This results in a 12-14% absolute risk reduction for the cranberry products (Raz 2004).

In an earlier large randomised double blind study conducted by Avorn et al (1994) it was revealed that elderly patients benefited from reduction of bacteriuria and pyuria after ingestion of cranberry juice, demonstrating a 42% less occurrence in the cranberry group compared with placebo. Another group of interest to benefit from cranberry and that was involved in a 2002 randomised placebo control trial were sexually active women who experienced recurrent UTIs. They were repeatedly shown to have a 50% reduction rate in disease and 50% decrease in antibiotic consumption (Stothers 2005).

Preliminary clinical evidence supports the use of cranberry (juice and capsules) for the prevention of urinary tract infections in healthy women over a 12 month period, and not as a first line agent for treatment. Jepson et al reported in a 2006 Cochrane Review the need for further well designed trials; multiple studies have had poor methodological quality with no clear dosing guidelines established. Undetermined is the effectiveness for groups such as the elderly and children. However evaluation of the total sum of favourable evidence combined with laboratory research tends to support cranberry's use in the urinary system; currently classified as a grade B (meaning good scientific evidence exists) (Jepson 2006, Ulbricht 2005).

Cranberry's anti-adhesion properties may also inhibit bacteria associated with gum disease and stomach ulcers (Cranberry Institute 2006).

Helicobacter pylori infections are increasingly being suggested as the cause of peptic ulcer development. It has been shown through in vitro studies that a high molecular weight constituent of cranberry juice inhibits adhesion of Helicobacter pylori to cultured human gastrointestinal cells (Burger 2002). At present there is no clinical evidence for human benefit, although there is suggestion that inhibition of H. pylori adhesion to the gastric mucus and stomach epithelium by cranberry will possibly benefit prevention of peptic ulcers in the future (Cranberry Institute 2006, Burger 2002).

In vitro studies have shown that the coaggregation of certain oral bacteria responsible for dental plaque and periodontal disease is reversed by 58% with cranberry juice treatment suggesting a possible role in oral hygiene. The author notes however that high fructose and dextrose content in some juice preparations may make the cranberry unsuitable (Weiss 1998). Yamanaka et al (2004) through his in vitro work continued to confirm that the exposure of cranberry juice has inhibitory effects on colonisation of oral streptococci to the tooth surface, thus revealing the high molecular mass constituent in cranberry can slow development of dental plaques. There is an evident need for clinical trials to begin in this area (Yamanaka 2004).

Other promising areas of investigation are in cancer prevention; various fractions of cranberry as evaluated by in vitro screening tests have demonstrated a potential anticarcinogenic activity (Bomser 1996). Significant reduction in breast tumors and delayed tumor development from treatment with cranberry solids compared to controls, are evident in more recent in vivo research. Tumor lines from skin, colon, lung and brain also showed intermediate sensitivity, blocking cell cycle progression and inducing these cells to undergo apoptosis (Ferguson 2004).

The free radical scavenging activity of cranberry's flavonol glycosides has been found to be superior to vitamin E. Yan et al (2004) support cranberry's protection against some cancers and cardiovascular disease prevention, identifying the berry's ability to inhibit low density lipoprotein oxidation as seen through his in vitro studies. In human trials, 500 mL of cranberry was favoured over blueberry juice when a significant increase in antioxidant plasma levels was shown after 60-120 minutes of ingestion, attributed to the ascorbic acid content in cranberry, which is absent in blueberry. The clinical significance of the antioxidant activity remains unclear (Pedersen 2000).

Urinary odour associated with incontinence or intermittent bladder catheterisation has been suggested in preliminary evidence to benefit from cranberry, especially for elderly nursing home patients. Although not clinically confirmed, due to the low toxicity levels of the berries, patients may choose to try cranberry for this purpose (Ulbricht 2005, Dorren 2005).

Based on theoretical reasoning, cranberry has been utilised for treatment of gout due to its ability to increase uric acid secretion. This indication is without clinical evidence, however this is a potential consideration for further research (Braun 2005).

Adverse reactions

Doses higher that 3L/day can result in gastrointestinal discomfort and diarrhea (Ulbricht 2005, Braun 2005).

Warnings and contraindications

In cases of acute urinary tract infections substitution of cranberry for antibiotics is not advised. Caution is suggested for patients with diabetes or glucose intolerance; commercially prepared cranberry juices can contain large quantities of sugar; patients who have a risk of kidney stones should also use with care due to cranberry's high level of oxalate.

Based on historical use many experts believed the consumption of cranberry is safe for pregnancy and lactation, however this has not been scientifically determined (Ulbricht 2005, Braun 2005, ADAM 2004).

Interactions

Warfarin (coumadin): A suggestion made in preliminary studies is that an interaction between warfarin and cranberry exists. The antioxidants, including flavonoids, in cranberry are known to inhibit cytochrome P450 enzymes and warfarin, processed by this path, may be affected. More studies are needed for clarification and for a final conclusion to be drawn (Ulbricht 2005, Dorren 2005).

Proton pump inhibitors (PPIs): Increased absorption of vitamin B12 in patients has been recorded in preliminary studies when taking cranberry juice concurrently with proton pump inhibitors (Ulbricht 2005).

Renally eliminated drugs and herbs: (Theoretically) the elimination of drugs excreted in urine could be enhanced by ingestion of cranberry juice (Ulbricht 2005).

Antacid drugs: (Theoretically) antacids may be counteracted by cranberry's acidic PH.

Antibiotics: (Theoretically) effects of antibiotics in the urinary tract could be increased by using cranberry (Ulbricht 2005).

Dosage: 18 years and older

There is no widely accepted standard for dosing; these studied doses are for prevention of urinary tract infections only.

UTI prevention

Juice: 300 mL has been demonstrated in well designed studies, the recommended dose ranges from 90-480 mL of cranberry juice cocktail twice daily or 1-30 mL of unsweetened 100% cranberry juice daily (Braun 2005, Ulbricht 2005).

Capsules: 300-400 mg of hard gelatine capsules of concentrated cranberry juice, twice daily, 1 hour before or 2 hours after meals with water (Ulbricht 2005).

Tincture: 4-5 mL of cranberry tincture, three times daily (Ulbricht 2005).

Juice verse capsules

Research results show there is no significant difference between incidences of UTI when using cranberry juice compared with cranberry tablets provided the right type of juice is selected (Raz 2004). However what needs to be considered is the leading brand of cocktail contains only 33% pure cranberry juice, with the rest of the juice comprised of water and sugar, resulting in a considerably higher calorie count than the tablet form. An inconvenience for the patient having to consume a larger amount of the juice exists, with the tablets having demonstrated a better cost effectiveness compared to the juice (Stothers 2002). In considering the best choice for clients, evaluation of these points suggests oral cranberry tablets appear a better option. Alternatively 100% cranberry concentrate should be used to ensure the strength of the therapeutic actives are present (Dorren 2005, Duke 2000).

The National Institutes of Health and National Centre for Complementary and Alternative Medicine Health have launched an initiative to provided approximately 2.6 million dollars in grants to build upon this foundation of evidence for cranberry treating and preventing urinary tract infections and other conditions. Appropriate forms of cranberry products, precise dosage levels, duration of treatment and further understanding into the mechanism of action for cranberry are to be concluded, with the primary interest to focus on cranberry juice cocktail and encapsulated powders (Dorren 2005, NIH 2005).

Conclusion

Enough positive evidence from studies drawn together suggests that the traditional use of cranberry for preventing and treating urinary tract infections is on the road to scientific clarification.

The direct ability of cranberry to affect bacterial attachment to cellular surfaces has warranted interest in further research in many other areas, for example oral hygiene, together with the fact that the berry's antioxidant activities provide disease treatment and/or prevention for cancer, heart, hyperlipidemia and Helicobacter pylori infection.

References

ADAM Inc. 2004 (last reviewed 2002). Cranberry. http://www.umm.edu/altmed/ConsHerbs/Cranberrych. html. Accessed 17 October 2006.

Avorn J, Monane M, Gurwitz JH, Glynn RJ, Choodnovskiy I, Lipsitz LA. 1994. Reduction of bacteriuria and pyuria after ingestion of cranberry juice. AMA 9:271(10);751-4.

Bomser J, Madhavi DL, Singletary K, Smith MA. 1996. In vitro anticancer activity of fruit extracts from Vaccinium species. Planta Med 62:3;212-6.

Braun L, Cohen M. 2005. Herb and Natural Supplements; An evidence-based guide. Australia: Elsevier Mosby.

Burger O, Weiss E, Sharon N, Tabak M, Neeman I, Ofek I. 2002. Inhibition of Helicobacter pylori adhesion to human gastric mucus by a high-molecular-weight constituent of cranberry juice. Crit Rev Food Sci Nutr 42:3;279-84.

Cranberry Institute. 2006. Emerging research. http://www.cranberryinstitute.org/healthresearch.htm. Accessed 29 October 2006.

Dorren R, Torkos S. 2005. Considering versatile cranberry. http://www.rhondadorren.com/images/article_Conside ring%20Versatile%20Cranberry%20Nat%20Pharm%2 0Final.pdf. Accessed 30 October 2006.

Duke JA. 2000. The Green Pharmacy: Herbal Handbook--your Comprehensive Reference to the Best Herbs for Healing. USA: St Martins Press.

Ferguson PJ, Kurowska E, Freeman DJ, Chambers AF, Koropatnick JD. 2004. A flavonoid fraction from cranberry extract inhibits proliferation of human tumor cell lines. Am Soc Nut Sci J Nutr 134;1529-35.

Foster S, Tyler VE. 1999. Tyler's Honest Herbal: A Sensible guide to the use of herbs and Related Remedies. 4th edn. New York: The Hawthorn Herbal Press.

Howell AB. 2002. Cranberry proanthocyanidins and the maintenance of urinary tract health. Crit Rev Food Sci Nutr 42:3;273-8.

Hutchinson J. 2005. Do cranberries help prevent urinary tract infections. Nurs Times 101:47;3840.

Jepson RG, Mihaljevic L, Craig J. 2006. Cranberries for preventing Urinary Tract infections. Cochrane Database Systemic Review, Issue 3. http://www.cochrane.org/reviews/en/ab001321.html. Accessed October 19 2006.

Kontiokari T, Sundqvist K, Nuutinen M, Pokka T, Koskela M, Uhari M. 2001. Randomised trail of cranberry lingonberry juice and Lactobacillus GG drink for the prevention of urinary tract infections in women. http://www.pubmedcentral.gov/articlerender.fcgi?artid =33514. Accessed 19 October 2006.

Lynch DM. 2004. Cranberry the prevention of Urinary Tract Infections. Am Fam Phys 10;2175-7.

National Institutes of Health (NIH). 2005 (last updated 30 May 2006). Cranberry. http://nccam.nih.gov/health/cranberry. Accessed 19 October 2006.

National Institutes of Health (NIH). 2005. Complementary and Alternative Medicine: Investigating the Science behind plants as treatments. http://nccam.nih.gov/news/newsletter/previous/index_ spring04.htm. Accessed 30 October 2006.

Pedersen CB, Kyle J, Jenkinson AMcE, Gardner PT, McPhail DB, Duthie GG. 2000. Effects of blueberry and cranberry juice consumption on the plasma antioxidant capacity of healthy female volunteers. Euro J Clinical Nut 54;405.

Raz R, Chazan B, Dan M. 2004. Cranberry juice and urinary tract infection. Clin Infect Disease 38;1413-19.

Siciliano AA. 1996. Cranberry. Herbalgram 38;51-3.

Sobota AE. 1984. Inhibition of bacterial adherence by cranberry juice: potential use for the treatment of urinary tract infections. J Urol 131;1013-16.

Stothers L. 2002. A randomized trial to evaluate effectiveness and cost effectiveness of naturopathic cranberry products as prophylaxis against urinary tract infection in women. Can J Urol 9:3;1558-62.

Ulbricht CE, Basch EM. 2005. Natural standard Herb & Supplement Reference: Evidence Based Clinical Reviews. US: Elsevier Mosby.

Ulbricht CE, Basch EM. 2005. Herb and supplement handbook: The clinical Bottom Line. USA: Elsevier Mosby.

Weiss E, Lev-dor R, Kashamn Y, Goldhar J, Sharon N, Ofek I. 1998. Inhibiting interspecies coaggregation of plaque bacteria with a Cranberry Juice Constituent. J Am Dent Assoc 129:12;1719-23.

Yan X, Murphy BT, Hammond GB, Vinson JA, Neto CC. 2002. Antioxidant activities and antitumor screening of extracts from cranberry fruit (Vaccinium macrocarpon). http://pubs.acs.org/cgibin/abstract.cgi/jafcau/2002/50/i 21/abs/jf0202234.html. Accessed 30 October 2006.

Yamanaka A, Kimizuka R, Kato T, Okuda K. 2004. Inhibitory effects of cranberry juice on attachment of oral streptococci and bioflim formation. Oral Microbiol Immunol 19;150-4.

Jade Mason

Email jmason@idl.net.au
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Title Annotation:Undergrad copy
Author:Mason, Jade
Publication:Australian Journal of Medical Herbalism
Geographic Code:8AUST
Date:Mar 22, 2008
Words:2575
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