Cranberry Juice and Urinary Tract Infection

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Table of Contents

Introduction
Cranberry: pharmacology and mechanisms of action
Uses and efficacy of cranberry juice
Cranberry juice: Evidence of efficacy
Conclusion
References

Introduction

Medicines of plant origin have been used by man in different cultures along history. Recently plant medicines have gained popularity because of safety, biological medicinal activity, and less cost. Urinary tract infection is a term that points to infection anywhere in the urinary tract although commonly linked to cystitis. Urinary tract infection is the second common type of infection caused in 80% of cases by gram-negat bacillus E. coli. Medicinal plants play a significant role in treating and preventing urinary tract infections as disinfectants, analgesics, and diuretics (Bag and colleagues, 2008). Cranberry is a low-lying evergreen vine that grows widely in the US and was first documented in 1614 by Captain John Smith, known as the admiral of New England. By 1686 it became popular to be considered with codfish and corn as the most prized American food (Cappelloni, 2002).

Recent evidence suggests that cranberry is effective in preventing urinary tract infection as it prevents E. coli from adherence to the walls of the urinary bladder (Bag and colleagues, 2008). The aim of this essay is to provide a brief review on the use of cranberry in preventing urinary tract infection.

Cranberry: pharmacology and mechanisms of action

Early research on cranberry use to prevent urinary tract infections suggested that its action in acidifying the urine is the main pharmacologic advantage (Lynch, 2004). However, current research centers on the role played by proanthocyanidins (cranberry falvonoids) to inhibit bacterial adherence to host tissues (Duguoa and others, 2008). Harkins (2000, pp. 9-12) suggested the fructose in cranberry contributes to its antibacterial action. Research suggested that proanthocyanidins are effective against many other microorganisms like P. aeuroginosa, K. pneumonia, P. mirabilis, and S. aureus. Evidence suggests that proanthocyanidins are effective also against H. pylori in the stomach, as well as against poliovirus (Duguoa and others, 2008). Evidence from recent studies suggests high level of antioxidants and anticarcinogenic effect of cranberry (Duguoa and others, 2008).

There are two E. coli strains responsible for urinary tract infection (UTI), a non-fimbriated and P-fimbriated type; the latter is responsible for the more serious UTI (acute pyelonephritis). Since the first step in developing infection is adherence of bacteria to target tissue surface, Liu and colleagues (2006, pp. 297-305) used Atomic Force Microscopy to study P-fimbriated strain bacterial adhesion and the effects of cranberry. Their results suggested that cranberry juice block the bacterial adhesive action after exposure period less than three hours. Not only that their finding suggested acidic medium is not needed to achieve such a block, which still occurs in PH 7. However, they did not show any effect of cranberry juice on fimbriae expression although evidence suggests there maybe interaction with bacterial DNA to inhibit fimbriae expression. They concluded that cranberry juice has an immediate effect on E. coli making the organism less adhesive and thus preventing infection (Liu and colleagues, 2006).

Greenberg and others (2005, p. 875) compared the antibacterial effect of dried cranberry raisins to that of the juice or sweetened juice cocktail in a pilot study. Data from this study showed a difference in bacterial anti-adhesion activity in human urine on using a single serving of sweetened dried cranberry and raisins where there was no effect. They suggested, because of the small sample, further investigation is needed, which may further enlighten the mechanism of cranberry action.

Uses and efficacy of cranberry juice

There is evidence suggesting cranberry juice is effective against Helicobacter pylori spiral organism blamed for nearly half the cases of gastric or duodenal ulcer, and is also effective against plaque bacteria causing periodontal disease. However, there is significant research pointing to its effectiveness in prevention of urinary tract infection (Lynch, 2004).

Raz and others (2004, p. 1417) reviewed the clinical studies on cranberry juice in urinary tract infection and inferred there is no enough evidence to suggest the fruit can be used in treating UTI. However, for prevention of UTI, evidence suggested the benefit of cranberry juice in prophylaxis from UTI, with sexually active adult females showing the strongest evidence. This group is followed by elderly group where using cranberry juice is successful in reducing bacteruria. They also noticed that clinical studies on patients with high risk of UTI (like patients with neurogenic bladder) are not enough to draw conclusions.

Females are at higher risk of having UTI than males, and the risk increases during pregnancy. Given the high safety profile of cranberry juice on the mother and the fetus makes it a suitable choice for prevention of UTI for females especially during pregnancy and lactation (Duguoa and others, 2008).

Kontiokari and others (2001, p.1) studied three groups of females with urinary tract infection caused by E. coli, the first group received cranberry lingonberry juice, the second received Lactobacillus GG drink, and the third control group received no intervention. Their results pointed to a significant difference in UTI recurrence rate among the three groups in favor of the first group. They inferred regular consumption of cranberry juice reduces the recurrence rate of UTI.

Wing et al (2008, p. 1367) studied the effects of cranberry juice on pregnant females with asymptomatic bacteruria. Results showed reduced frequency of recurrent asymptomatic bacteruria and UTI on daily drinking of cranberry juice. Thus, they inferred the juice has a preventive effect against UTI during pregnancy.

Older people are the second common group to suffer from UTI (Raz et al, 2004). McMurdo et al (2005, p. 256) examined the potential of cranberry juice in preventing UTI in hospitalized elderly. Results suggested significant reduction of UTI caused by E. coli in the group receiving cranberry juice compared to control; however, the overall rate of UTI showed no significant difference between the two groups.

Cranberry juice: Evidence of efficacy

Cranberry juice or in tablet forms with increased fluid intake was found more effective than increased fluid intake alone in preventing UTI in sexually active females. Stothers (2002, p.1561) inferred if cranberry juice or products are added to the conservative measure of increased fluid intake to prevent UTI in this group, this would result in 10 to 15% lesser incidence of recurrent UTI. Di Martino and colleagues (2006, pp.21-27) tested the in vitro anti adherence activity of cranberry juice on E. coli strains. They reported the resulting decrease in bacterial adherence is dose-dependent and occurs unlinked to gene encoding or antibiotic resistance phenotype. Besides, they report that cranberry juice affects adherence of E. coli strains. McMurdo and colleagues compare cranberry extract to small doses of trimethoprim for prophylaxis of urinary tract infection in elderly females. Their results suggested a narrow advantage of low doses of trimethoprim over cranberry extracts in preventing recurrent UTI in older females. Given the higher safety, lack of resistance, and absent fungus superimposed infection, they inferred cranberry extract can be a successful measure to prevent recurrent UTI in this group of patients.

Tong and others (2006, p. 1417) examined the potential of cranberry juice in the treatment of UTI by examining the antibacterial activity of cranberry juice in urine. The result showed that urine collected after drinking cranberry juice does not have either bactericidal or bacteriostatic activity against E. coli. They inferred that efficacy of cranberry juice in UTI prevention is because of its anti adherence effect combined with factors other than antibiotic like effect. Therefore, they could not recommend therapeutic use of cranberry juice in UTI treatment.

Contraindications, drug interaction and side effects of cranberry juice Cranberry fruit (processed or not) has good safety profile despite the lack of long-term safety data as a drug. Cranberry use is reported to increase the absorption of vitamin B12 in patients receiving proton pump inhibitors for the treatment of gastric ulcers. Because of it its effect acidifying the urine, cranberry may cause the kidneys to excrete weakly alkaline drugs (like antidepressants) more quickly; thus reducing their effectiveness (Lynch, 2004).

Cranberry may cause significant rise in the urinary oxalate level; therefore with excessive use (around four liters a day), individuals with tendency to form urinary tract stones may be at increased risk. Excessive use may also be associated with gastrointestinal upsets like diarrhea especially in children and young adults (Duguoa and others, 2008).

Cranberry is not known to interact with drugs; however, there are reports of interaction with warfarin. These reports point to increased antithrombotic effects of warfarin when administered in patients receiving cranberry fruits. This may be because the juice inhibits the activity of cytochrome P450-2C9 enzyme responsible for metabolism of S-warfarin (metabolized derivative responsible for anticoagulant effect) resulting in higher plasma levels and accordingly increased anticoagulant effect (Greenblatt and von Moltke, 2005).

Conclusion

There is evidence that cranberry juice is useful to prevent urinary tract infections especially in adult sexually active females. However there is no clear evidence about the amount and concentration to be takes, therefore further research is needed to determine its efficacy in prevention of UTI in susceptible population. There is a need to study the effect of other forms of cranberry as capsules, tablets or other products.

References

Bag, A., Bhattacharyya, S.K., and Chattopadhyay, R.R. (2008). Medicinal Plants and Urinary Tract Infections: An update. PHCOG. REV., 2(4), 277-284.
Cappelloni, N. (2002). Cranberry Cooking for All Seasons. New Bedford, Ma: Spinner Publications.
Di Martino, P., Angiel, R., David, K. et al (2006). Reduction of Escherichia coli adherence to uroepithelial bladder cells after consumption of cranberry juice: a double-blind randomized placebo-controlled cross-over trial. World J Urol, 24, 21-27.
Dugoua, J-J., Seely, D., Perri, D. et al (2008). Safety and Efficacy of Cranberry (Vaccinium Macrocapron) During Pregnancy and Lactation. Can J Clin Pharmacol, 15(1), e80-e86.
Greenberg, J.A., Newman, S.J., and Howell, A.B. (2005). Consumption of Sweetened Dried Cranberries Versus Unsweetened Raisins for Inhibition of Uropathogenic Escherichia coli Adhesion in Human Urine: A Pilot Study. The Journal of Alternative and Complementary Medicine, 11(5), 875-878.
Greenblatt, D.J., and von Moltke, L.L. (2005). Interaction of warfarin with drugs, natural substances, and foods. J Clin Pharmacol, 45, 127-132.
Harkins, K. (2000). What’s the use of cranberry Juice? Age and Ageing, 29, 9-12.
Kontiokari, T., Sundqvist, K., Nuutinen, M. et al (2001). Randomized trial of cranberry-lingonberry juice and Lactobacillus GG drink for the prevention of urinary tract infections in women. BMJ, 322, 1-5.
Liu, Y., Black, M.A., Caron, L., and Camesano, T.A. (2006). Role of Cranberry Juice on Molecular-Scale Surface Characteristic and Adhesion Behavior of Escherichia coli. Biotechnol Bioeng., 93(2), 297-305.
Lynch, D.M. (2004). Cranberry for Prevention of Urinary Tract Infections. Am Fam Physician, 70, 2175-2177.
McMurdo, M.E.T., Bisset, L.Y., Price, R.J.G. et al (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, 256-261.
McMurdo, M.E.T, Agro, I., Phillips, G. et al (2009). Cranberry or trimethoprim for the prevention of recurrent urinary tract infection? A randomized controlled trial in older women. Journal of Antimicrobial Chemotherapy, 63, 389-395.
Raz, R., Chazan, B., and Dan, M. (2004). Cranberry Juice and Urinary Tract Infection. Clinical Infectious Diseases, 38, 1413-1419.
Stothers, L. (2002). A randomized trial to evaluate effectiveness and cost effectiveness of naturopathic cranberry products as prophylaxis against urinary tract infection in women. The Canadian Journal of Urology, 9(3), 1558-1562.
Tong, H., Heong, S., and Chang, S. (2006). Effect of ingesting cranberry juice on bacterial growth in urine. Am J Health-Syst Pharm, 63, 1417-1419.
Wing, D.A., Rumney, P.J., Preslicka, C.W., and Chung, J.H. (2008). Daily Cranberry Juice for the Prevention of Asymptomatic Bacteruria in Pregnancy: A Randomized, Controlled Pilot Study. The Journal of Urology, 180, 1367-1372.

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