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Date Last Updated: 28/10/04

Cranberry for the prevention of urinary tract infection


Photographer: Robert R. Kowal, University of Wisconsin-Madison, USA. Obtained from Wisconsin State Herbarium, USA

Overview

A urinary tract infection is the over abundance of certain bacteria in the urinary tract, causing a variety of symptoms including pain upon urination, increased frequency of urination, cloudy urine, blood and pus in the urine, fever, tiredness, and vomiting. Cranberries (mainly the juice) are often used by people to help prevent urinary tract infections. This evidence summary identified one systematic review and nine clinical trials (involving a total of 689 people) on the use of cranberries for the prevention of urinary tract infection. The systematic review concluded that there is some evidence (based on findings from two randomised clinical trials involving 300 participants) that cranberries may reduce the number of urinary tract infections that have symptoms over a six to 12-month period, in women with frequent urinary tract infections. However, the effect of cranberries on urinary tract infections in other groups, such as children, elderly men and women, and people with spinal cord injuries, is not clear. Side effects related to the use of cranberries for urinary tract infection tend to be uncommon, mild and reversible, and include nausea, gastrointestinal upset, diarrhoea, and bitter taste. Side effects associated with the long-term use of more than one litre of cranberry juice per day include gastrointestinal upset, diarrhoea and an increased risk of kidney stone formation. Although rare, serious side effects associated with the consumption of cranberries have been reported. Five cases of increased bleeding, in people taking warfarin (coumadine), after consuming cranberry juice have been reported.


Background


Urinary Tract Infection
A urinary tract infection is the presence of a certain amount of bacteria in the urinary tract1-4. Women are more likely to experience urinary tract infections than men1-3, and up to 50% of all women are estimated to be affected by this condition at some stage of their lives2. Furthermore, children under two5, pregnant women, elderly men and women, people who have catheters (medical tubes to empty the bladder) as a result of spinal cord injury, people with diabetes, multiple sclerosis, or other chronic diseases are more prone to develop urinary tract infections than other people2, 4. Symptoms of a urinary tract infection may include mild discomfort while urinating, increased frequency of urination, cloudy urine, blood in the urine (haematuria), pus in urine (pyuria), pain on passing urine (dysuria), fever, tiredness (lethargy), and vomiting (especially in children)4, 6. In some instances a urinary tract infection can occur without symptoms (called asymptomatic bacteriuria)2, 4. The usual treatment for urinary tract infection is antibiotics7. Antibiotics are also used to help prevent urinary tract infections in susceptible people. However, an increasing number of urinary tract infections are caused by bacteria that are resistant to commonly used antibiotics1,8-10. Cranberry juice is also used by some people to help prevent urinary tract infections3.

Cranberry
Cranberry (Vaccinium macrocarpon) is an evergreen shrub which grows in most temperate climates11, 12. It is also known as American Cranberry, European Cranberry, Large Cranberry12, and marsh apple11. The ripe fruit of the cranberry is the part of the plant most commonly used for medical purposes, including the treatment of bladder and kidney disease13, the prevention of urinary tract infections3, 14, and the prevention of blockages in urinary catheters12. Cranberries are also used to disguise the smell of urine in people with urinary incontinence. Full strength cranberry juice is very acidic and unpalatable15, consequently most cranberry juice on the market contains about 30% pure cranberry juice, plus some form of sweetener, water, and added vitamin C15.


Evidence reviewed in this summary


Efficacy information
  • Systematic reviews: One systematic review on the use of cranberry for the prevention of urinary tract infections was identified for this evidence summary3. This review was conducted by the Cochrane renal group and was last updated on the 23rd February 2004. Two narrative reviews on cranberry juice and urinary tract infections15, 16, and one narrative review on prevention of urinary tract infections in spinal cord injured patients9 were also identified for this evidence summary.
  • Clinical trials: The above systematic review identified seven randomised controlled clinical trials on cranberry for the prevention of urinary tract infections13, 17-22. Since the systematic review was published, two additional clinical trials (involving 37 and 48 people - a total of 85 participants) have been conducted on the effect of cranberry juice for preventing recurrent urinary tract infections in people with spinal cord injury who use medical tubes to empty the bladder at varying intervals (intermittent catheterisation)23, 24. No clinical trials on the use of cranberry for preventing urinary tract infections are known to be currently underway (www.controlled-trials.com).
  • Case-control studies/Cohort studies/Case studies: Given the extensive coverage of the above systematic review, no case-control, cohort studies or case studies were assessed for this evidence summary.
Safety information
  • Systematic reviews: The systematic review3 identified in the efficacy section above summarised information on the side effects of cranberry.
  • Clinical trials: The seven clinical trials identified by the above systematic review reported data on side effects, as did the two recently conducted trials13, 17-24.
  • Other studies: Side effects related to the use of cranberry in general have been reported by the Committee on Safety of Medicines in the United Kingdom, Natural database internet sources and also from the United States Food and Drug Administration, Special Nutritionals Adverse Event Monitoring System12, 25.

              
          Evidence on efficacy


          Information on the use of cranberry for preventing urinary tract infection is available from one systematic review3, three narrative reviews9, 15, 16 and nine randomised clinical trials13, 17-24, representing 689 participants aged between 1-81 years. Trials ranged in size between 15 and 192 people and treatment periods varied between eight weeks and 12 months. Eight trials involved a highly selected group of people (e.g. spinal cord injured patients, patients at high risk of developing urinary tract infection, or women) and one focused on the general population. Results from the systematic review (that included seven of the trials and involved a total of 604 people) indicated that only three trials involved more than 100 people and many participants did not complete the trials they were involved in. For example, one trial had 58% of participants who originally took part in the trial withdraw19 and another had 47% withdraw18. Comparability of the trial results is made all the more difficult by the differing treatment periods and the fact that various types (eg. juice concentrate, juice cocktail, and cranberry capsules/tablets), concentrations and doses of cranberry products were tested. For example, preparations and doses varied between 150-600ml of cranberry juice daily (30% cranberry concentrate), to 300-400mg of standardised extract twice daily (dried cranberry powder in the form of capsules and tablets3, 15). Given this variability in study design and conduct, findings from the systematic review are based on combined results from only two trials13, 20. Overall results indicate that compared to a placebo, cranberry juice and tablets may reduce the risk of developing symptomatic urinary tract infection in sexually active women over a 12-month period. Furthermore, cranberry juice appears to reduce the risk of developing a urinary tract infection after six months in women who have frequent urinary tract infections, compared to no intervention. However, this effect was not clear for the other patient groups, such as children and elderly men and women. Specific details on the trials assessed in the systematic review are as follows:
          • One double-blind trial compared the effect of cranberry juice and cranberry tablets to a placebo on urinary tract infections in 150 sexually active women13. In those women taking cranberry juice over a year, there was a 12% reduction in the risk of developing at least one urinary tract infection, compared to those taking placebo juice. In those women taking cranberry tablets over a year, there was a 14% reduction in the risk of developing at least one urinary tract infection, compared to those taking placebo tablets.
          • One open (not blinded) trial involving 150 women who had had a urinary tract infection in the past year showed that a six month course of cranberry juice reduced the risk at six months of developing a urinary tract infection by 20%, compared to no intervention20. However, no significant difference between the groups was found at 12 months.
          • In the remaining five trials, four (involving a total of 285 people)17-19, 21 compared cranberry juice (cocktail) to a placebo drink and one (involving 19 women)22 compared cranberry capsules to placebo capsules. All five trials included only a small number of participants, were of poor methodological quality, and provided insufficient evidence on the use of cranberry for preventing urinary tract infections3, 15.
          Results from the narrative reviews9, 15, 16 were consistent with these findings. Results from the two trials published after the Cochrane review showed that cranberry (juice, tablet, capsule) was not effective in reducing the risk of developing recurrent urinary tract infection in people with spinal cord injury23, 24.


          Evidence on safety


          Evidence from one systematic review3 and nine clinical trials13, 17-24 on cranberry for the prevention of urinary tract infections showed that side effects associated with the consumption of cranberry are uncommon, mild, and reversible.
          • One double-blind randomised trial (involving 150 women) reported that 6% of people taking cranberry juice complained of reflux (upward flow of food), with two of the three women not completing the study because of this13. Furthermore, 8% of people taking the cranberry tablet complained of mild nausea compared to 4% of people taking the placebo. Two percent of people taking the cranberry tablet also complained of increased frequency of bowel movements whereas no one in the placebo group reported this effect.
          • One person in another double-blind trial (involving 37 people with spinal cord injury) had abdominal discomfort that he attributed to cranberry tablets and withdrew from the study23. Of the other 15 people who withdrew from the study six people decided to stop the study for no specific reason, and the remaining nine people did not attribute their withdrawal to cranberry.
          • One non-blinded randomised trial (involving 150 women) reported that apart from occasional complaints about the bitter taste of the cranberry juice, no adverse events were reported20.
          • One single-blind randomised trial (involving 40 children aged 1-18 years) reported that 89% of the children taking cranberry cocktail juice did not complete the trial for reasons directly related to the cranberry18. Seventy percent of the children complained of bitter taste, and 12% complained of caloric load (cranberry juice added extra calories).
          • There is one report of an allergic reaction associated with the consumption of cranberry juice13.The remaining five trials provided limited to no information on side effects. One trial did not report data on side effects17. In two trials no side effects were reported by participants21, 22. In one of these trials22, the nine withdrawals from the study were not related to cranberry. One trial reported that one of the reasons cited by participants for not completing the study was that taking the cranberry pills caused adverse effects. However, these effects were not specified24. The other trial did not state why 55% of randomised participants did not finish the study19.

          In very large doses (for example three to four litres per day) cranberry juice can cause gastrointestinal upset and diarrhoea12. Prolonged use of cranberry juice in large doses (more than one litre per day) may increase the risk of kidney stones formation12, 26.
          A number of more serious side effects have been reported on the use of cranberry in general. Since 1999, the Committee for Safety of Medicines in the United Kingdom has received five reports of increased INR (International Normalised Ratio, the test for increased bleeding tendency) in patients taking warfarin (Coumadine) and cranberry juice25. One of the cases proved fatal (a man died of internal bleeding after drinking cranberry juice over a six week period).


          Cited references

          To find out more about any of the references listed below go to the "About page" of this website and read the section titled "How can referenced articles be obtained."

          1. Uehling D, Hopkins W, Elkahwaji J, Schmidt D, Leverson G. Phase 2 clinical trial of a vaginal mucosal vaccine for urinary tract infections. Journal of Urology 2003;170(3):867-869.
          2. Foxman B. Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Disease-a-Month 2003;49(2):53-70.
          3. Jepson R, Mihaljevic L, Craig J. Cranberries for preventing urinary tract infections. [Systematic Review]. Cochrane Database of Systematic Reviews 2004;2.
          4. Stamm W. Acute UTIs: urethritis, cystitis, and pyelonephritis. In: Braunwald E, Fauci AS, Isselbacher KJ, Kasper DL, Hauser SL, Longo DL, et al., editors. Harrison's online. New York: McGraw Hill; 2004. p. Chapter 280. Urinary tract infections and pyelonephritis.
          5. Verrier-Jones K, Hockley B, Scrivener R, Pollock J. Diagnosis and management of urinary tract infections in children under two years: assessment of practice against published guidelines. London: Royal College of Paediatrics and Child Health; 2001.
          6. Haslett C, Chilvers E, Boon N, Colledge N, Hunter J, editors. Davidson's principles and practice of medicine. 19th ed. Edinburgh: Churchill Livingstone; 2002.
          7. Pittler M. Regular drinking of cranberry-lingonberry juice seems to reduce the recurrence of urinary tract infection. Focus on Alternative & Complementary Therapies 2001;6(4):258-259.
          8. Gupta K, Scholes D, Stamm W. Increasing prevalence of antimicrobial resistance among uropathogens causing acute uncomplicated cystitis in women.[see comment]. JAMA 1999;281(8):736-738.
          9. Trautner B, Darouiche R. Prevention of urinary tract infection in patients with spinal cord injury. Journal of Spinal Cord Medicine 2002;25(4):277-283.
          10. Uehling D, Hopkins W, Beierle L, Kryger J, Heisey D. Vaginal mucosal immunization for recurrent urinary tract infection: extended phase II clinical trial. Journal of Infectious Diseases 2001;183(Suppl 1):81-83.
          11. Ernst E, Pilter M, Stevinson C, White A. The desktop guide to complementary and alternative medicine: an evidence-based approach. London: Mosby; 2001.
          12. Natural Medicines Comprehensive Database. Cranberry. Therapeutic Research Center, Stockton, CA.; Available by subscription from: http://www.naturaldatabase.com Accessed on 30.8.04.
          13. 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.
          14. Jepson R, Mihaljevic L, Craig J. Cranberries for treating urinary tract infections. The Cochrane Library, 2004;1.
          15. Raz R, Chazan B, Dan M. Cranberry juice and urinary tract infection. Clinical Infectious Diseases 2004;38(10):1413-1419.
          16. Lowe F, Fagelman E. Cranberry juice and urinary tract infections: What is the evidence? Urology 2001;57(3):407-413.
          17. Avorn J, Monane M, Gurwitz J, Glynn R, Choodnovskiy I, Lipsitz L. Reduction of bacteriuria and pyuria after ingestion of cranberry juice. JAMA 1994;271(10):751-754.
          18. Foda M, Middlebrook P, Gatfield C, Potvin G, Wells G, Shillinger J. Efficacy of cranberry in prevention of urinary tract infection in a susceptible pediatric population. Canadian Journal of Urology 1995;2(1):98-102.
          19. Haverkorn M, Mandigers J. Reduction of bacteriuria and pyuria using cranberry juice. JAMA 1994;272(8):590.
          20. Kontiokari T, Sundqvist K, Nuutinen M, Pokka T, Koskela M, Uhari M. Randomised trial of cranberry-lingonberry juice and Lactobacillus GG drink for the prevention of urinary tract infections in women. BMJ 2001;322(7302):1571.
          21. Schlager T, Anderson S, Trudell J, Hendley J. Effect of cranberry juice on bacteriuria in children with neurogenic bladder receiving intermittent catheterization.[see comment]. Journal of Pediatrics. 1999;135(6):698-702.
          22. Walker E, Barney D, Mickelsen J, Walton R, Mickelsen R. Cranberry concentrate: UTI prophylaxis. Journal of Family Practice 1997;45(2):167-168.
          23. Linsenmeyer T, Harrison B, Oakley A, Kirshblum S, Stock J, Millis S. Evaluation of cranberry supplement for reduction of urinary tract infections in individuals with neurogenic bladders secondary to spinal cord injury. A prospective, double-blinded, placebo-controlled, crossover study. Journal of Spinal Cord Medicine 2004;27(1):29-34.
          24. Waites K, Canupp K, Armstrong S, DeVivo M. Effect of cranberry extract on bacteriuria and pyuria in persons with neurogenic bladder secondary to spinal cord injury. Journal of Spinal Cord Medicine 2004;27(1):35-40.
          25. Committee on the Safety of Medicines. Possible interaction between warfarin and cranberry juice. Current Problems in Pharmacovigilance 2003;29:8.
          26. Uehling D, Hopkins W, Elkahwaji J, Schmidt D, Leverson G. Phase 2 clinical trial of a vaginal mucosal vaccine for urinary tract infections. Journal of Urology 2003;170(3):867-869.


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