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The role of cranberry in disease prevention

Stewart E Glaspole
BSc(Hons) PGCert MRPharmS
Senior Clinical Lecturer in Pharmacology and Therapeutics
Brighton and Sussex University Hospitals NHS Trust
E:glaspole@nhs.net

The American cranberry is an indigenous fruit of the North American continent. Although native Americans did not cultivate it, there is evidence dating back to the 15th century indicating that the fruit was used for such maladies as blood poisoning and wound infections.(1) Early settlers first named the fruit the craneberry as the developing flowers resembled the crane, as well as being a particularly favoured foodstuff of the bird.
Today, as a result of advanced harvesting techniques  there are 50,000 acres worldwide producing cranberries, much of which will appear on supermarket shelves as cranberry juice drinks.

Urinary tract infections
In modern-day medicine, the use of cranberry was first recognised as an efficacious treatment in urinary tract infections by Blatherick in 1914.(2) At this time it was thought that acidification of the urine (from hippuric acid - a cranberry component) was the healing effect. Subsequent in-vitro studies have shown that cranberry can prevent the adhesion of pathogenic Escherichia coli to uroepithelial cells.(3)
The results of the first randomised controlled trial looking at the effects of commercially available cranberry juice drinks were published in 1994. A total of 153 elderly women given 300ml of cranberry juice drink daily had a significantly reduced incidence (58%) of bacteriuria and pyuria compared with the placebo group.(4)
In a subsequent 12-month follow-up trial, 150 women with urinary tract infections caused by E coli were randomised to receive 50ml of a cranberry-lingonberry juice drink , 100ml lactobacillus drink or no intervention. The results of the study showed a 20% reduction in absolute risk of symptomatic reinfection compared with the placebo group.(5)

Cardiovascular events
There is still much debate regarding the use of cranberry in halting cardiovascular events. Cranberries contain thousands of active chemical compounds, the activities of many of which are not known. It is known, however, that the flavonoids contained in cranberries have a wide spectrum of physiological activities, which include:

  • Inhibition of low-density lipoprotein oxidation.
  • Inhibition of platelet aggregation and adhesion.
  • Alteration of lipid enzyme metabolism.
  • Effects on endothelium-dependent vasorelaxation.

Whereas specific trials have not been designed to study these outcomes, this is a promising area nonetheless, and one that will undoubtedly provoke stimulating debate.(6)

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Helicobacter pylori eradication
For some time there has been a known link between peptic ulcers and H pylori infection. Peptic ulcers have been found in 25% of dyspeptic patients whose blood tests positive for H pylori, compared with only 3% of similar patients who test negative.(7) One in-vitro study has shown that a high molecular constituent of cranberry juice prevents the adhesion of H pylori to the gastric mucosa.(8) This effect is probably mediated in a similar way to E coli adhesion, since H pylori are also flagellated bacteria.

Drug interactions
One area of current debate is the possible interaction between warfarin and cranberry juice. At present, it is thought that the flavonoids contained within the cranberry inhibit cytochrome P450, the liver enzyme responsible for the metabolism of warfarin.(9) The interaction requires further investigation, but it should be noted that many therapies are used successfully even when interactions are present - aspirin and warfarin being a prime example. With regular INR testing (which should always be carried out with warfarin therapy) and adequate patient counselling, cranberry can still be used concomitantly with warfarin.

Research
Over 95% of the research to date uses a juice with a high cranberry content (25% concentration). Patients may not be aware of the differing levels of cranberry concentrate contained in commercially available juice drinks. The Cranberry Information Bureau (see Resources) provides details of commercially-available products at this concentration.

Conclusion
Multinational pharmaceutical companies are among the only organisations that can fund and support good-quality randomised controlled trials. As healthcare professionals, we are told that this evidence is the most robust and relevant to patient care. However, it is argued that where such investment into clinical trials is not available, the usefulness of smaller studies should not be discounted. With prudent selection of the correct candidates, and a holistic attitude to treatment, there is undoubtedly a niche for nutriceutical therapies.

References

  1. Eck P. The American cranberry. New Jersey, USA: Rutgers University Press; 1990.
  2. Blatherwick NR. The specific role of foods in relation to the composition of the urine. Arch Int Med 1914;14:409-50.
  3. Schmidt DR, Sobota AE. An ­examination of the anti-adherence activity of cranberry juice on urinary and nonurinary bacterial isolates. Microbios 1988;55:173-81.
  4. Avorn J, Monane M, Gurwitz JH, et al. Reduction of bacteriuria and pyuria after ingestion of cranberry juice -a reply. JAMA 1994;272:589-90.
  5. Kontiokari T, Sundqvist K, Nuutinen M, et al. Randomised trial of cranberry- lingonberry juice and lactobacillus GG drink for the prevention of urinary tract infections in women. BMJ 2001;322:1-5.
  6. Reed J. Cranberry flavonoids, ­atherosclerosis and cardiovascular health. Crit Rev Food Sci Nutr 2002;42 Suppl:301-16.
  7. Moore RA. Helicobacter pylori and peptic ulcer. A systematic review of ­effectiveness and an overview of the economic benefits of implementing what is known to be effective. Oxford: Health Technology Evaluation Association; 1995.
  8. Burger O, Weiss E, Sharon N, et al. Inhibition of Helicobacter pylori ­adhesion to human gastric mucus by a high-molecular weight constituent of cranberry juice. Crit Rev Food Sci Nutr 2002;42 Suppl:279-84.
  9. Rettie AE, Korzekwa KR, Kunze KL, et al. Hydroxylation of warfarin by human cDNA-expressed cytochrome P-450: a role for P-4502C9 in the ­etiology of (S)-warfarin-drug ­interactions. Chem Res Toxicol 1992;5:54-9.

Resources
The Cranberry Institute
Specialises in the dissemination of health-related information regarding ­cranberry
W:www.cranberryinstitute.org
Cranberry Information Bureau Field McNally Leathes Limited
Field House
8 High Street
Hurstpierpoint
West Sussex
BN6 9TY
E:siobhan@fml-pr.co.uk

Events
Cranberry Symposium
A London-based meeting, held in November 2004, brought together ­international scientists to ­present and debate latest research into cranberry and its health ­properties.
W:www.cransym. org