Date Last Updated: 24/02/06
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Cranberries for preventing urinary tract infections

Contents

1.         Abstract
2.         Type of treatment
3.         Background
4.         Objectives
5.         Criteria for including studies
6.         Search strategy
7.         Methods
8.         Description of studies
9.         Methodological quality
10.       Results
11.       Discussion of Findings
12.       Conclusions
13.       References
 

1. Abstract
 Urinary tract infections (UTIs) are very common, especially in women and older people. They are usually caused by infection of the urinary tract by bacteria from the bowel, most commonly Escheria coli (E. coli).

Typical symptoms include a frequent and/or urgent need to pass urine or a burning sensation when passing urine. The diagnosis is confirmed by a urine test, which measures the amount of bacteria in the urine.

Cranberries contain substances that make it hard for bacteria to stick on the walls of the bladder. Cranberry juice has traditionally been used to reduce bladder and other urinary tract infections in high risk groups such as older people.

There was good evidence from a Cochrane systematic review [link to reference] that cranberry products such as juice and capsules can prevent recurrent UTIs in women. There was insufficient evidence to show whether cranberries are also effective for preventing UTIs in other groups, nor is there evidence as to which form or dose of cranberry is most effective.

There was no good evidence that cranberry products have adverse events. However, one trial found that 25% of children found the taste unpleasant.

2. Type of treatment Cranberry
    Scientific name (genus and species) Vacciniun macrocarpon
    Synonyms and Common names American cranberry, Bog cranberry
    Indication Prevention of urinary tract infections

3. Background
Urinary tract infections (UTIs) are usually caused by infection of the urinary tract by bacteria from the bowel, which live on the skin in the rectal area. The bacteria travel upwards through the urinary tract and may cause infection, most commonly in the bladder (cystitis), but also other areas such as the kidneys or urethra. UTIs are very common, especially in women, probably because women have a shorter urethra than men that allows bacteria to ascend more easily into the bladder. It has been estimated that 30 per cent of women suffer from the symptoms of cystitis at some stage during their lives (Kelly 1977).

Typical symptoms include a frequent or urgent need to pass urine or a burning sensation when passing urine (or a combination of these). Kidney infection (pyelonephritis) tends to cause flank pain and fever. Children typically develop a high fever and generalised symptoms such as tiredness, vomiting and poor feeding (Jepson 2004).

UTI may be diagnosed by the symptoms alone or by testing the urine for the presence of large numbers of bacteria: a threshold of over 100,000 bacteria per ml is normally used to confirm the diagnosis. However, the symptoms of UTI may occur without high bacteria counts, in a common condition that is called urethral syndrome. Similarly, high bacteria counts may be present without symptoms (asymptomatic UTI). Some people are prone to recurrent UTIs, which may occur two to three times per year (Roberts 1979; Wong 1984).

People who are at increased risk of urinary tract infection include the following groups:

• those who have had one or more UTIs in the past
• pregnant women
• the older

• people with urinary catheters

• people with an abnormality of the urinary tract.

Cranberry juice has traditionally been used for preventing urinary tract infections. Its effect may be due to its ‘antiadhesive’ properties, as it has been demonstrated that cranberries contain compounds that prevent common bacteria (such as E. coli) from sticking to the lining of the bladder (Zafriri 1989).

The aim of this review was to assess the effectiveness of cranberries in the prevention of UTIs in susceptible populations. Although the juice of cranberries is the form of cranberry most widely used for the prevention of UTIs, related products include cranberry powder in hard or soft gelatin capsules.
 

4. Objectives
To assess the potential benefits and harms of cranberries for the prevention of urinary tract infections.

5. Criteria for including studies
·        Types of study: published systematic reviews or randomised controlled trials (RCTs) of cranberry
       juice (or derivatives) versus placebo, no treatment or any other treatment.

·        Types of participants: adults or children at high risk of urinary tract infection.

·        Types of intervention: cranberry juice or a cranberry product such as capsules, taken for at least one month.

·        Types of outcome measure: number of UTIs (with or without symptoms), compliance with treatment and adverse events.

 ·        Exclusions: studies of cranberry for the treatment of UTI were excluded, as were studies of non-bacterial UTI.

6. Search strategy
The following databases were searched in December 2005: AMED, The Cochrane Library, MEDLINE, EMBASE, CINAHL. The reference lists of publications retrieved by the search for further relevant studies were checked.

7. Data Collection, Analysis and Development of Recommendations
We used the above search strategy to obtain titles and abstracts of studies that were potentially relevant to this review. Where studies met the criteria for inclusion, they were assessed in full text. The quality of each study was evaluated using the SIGN criteria (http://www.sign.ac.uk/methodology/checklists.html) for the evaluation of RCTs and systematic reviews.Where primary studies were included in a good quality systematic review, the systematic review was included rather than the individual primary studies.

The overall quality of the body of evidence (considering all the included studies) was graded according to the CEBM levels of evidence system (www.cebm.net/levels_of_evidence.asp).

Relevant data were extracted from the studies selected for inclusion.

8. Description of studies
Two studies met the criteria for inclusion, comprising a Cochrane systematic review of randomised and quasi-randomised controlled trials of cranberries for UTI prevention (Jepson 2004) and one RCT published since the publication of the systematic review (McMurdo 2005).

Summary details of the trials included in the systematic review are as follows:

Study	Participants		Intervention & Comparison	Outcomes measured	Comment
Avorn 1994 (Also reported in Avorn 1993)   USA	192 older women in institutional care or sheltered accomodation, mean age 78.5		300 ml cranberry juice cocktail (30% cranberry concentrate) daily vs placebo that looked and tasted similar for 6 months	·     Bacteria count	Quasi-randomised Double blinded Poor reporting 20% loss to follow up/withdrawals, reasons not stated Industry funded
Foda 1995   Canada	40 children aged 1-18 with neuropathic bladder and intermittent catheterisation		Cranberry cocktail (30% cranberry concentrate) daily vs water for 6 months	·      Number of months of positive culture plus symptomatic or asymptomatic UTI	RCT Randomisation method not stated Cross over design 47% loss to follow up/withdrawals (19/40), reasons stated
Haverkorn 1994 The Netherlands	38 older men and women (mean age 81)		30 ml cranberry juice mixed with water vs same volume of water for 4 weeks	·      Bacteria count	Quasi randomised Crossover design 58% loss to follow up/withdrawals (22/38), reasons unclear
Kontiokari 2001 Finland	150 women in Finnish student health service with UTI caused by E. coli. Mean age 29-32 yrs		50 ml cranberry & lingonberry juice concentrate (7.5g cranberry concentrate) daily for 5 days per week for 6 months vs 100 mls lactobacillus GG drink daily for for five days per week for 12 months vs no treatment	·      Recurrent symptomaticUTI (after clearance of UTI at study entry)	RCT Unblinded 8% (13/150) losses to follow up/withdrawals, reasons given Stopped early as cranberry juice supplier stopped production Analysed by intention to treat
Schlager 1999   USA	15 children aged 2-18 yrs with neuropathic bladder and intermittent catheterisation		300 ml cranberry juice daily vs similar looking and tasting placebo for 3 months each	·      Bacteria count ·      Symptomatic UTI	RCT Double blind Cross over design
Stothers 2002 Canada	150 sexually active women aged 21-72 yrs with hx of recurrent UTI		Placebo juice + cranberry tablets twice daily vs Cranberry juice 250 mls 3 times daily + placebo tablets vs Placebo juice + placebo tablets for one year	·      Symptomatic UTIs per year ·      Annual antibiotic consumption ·      Cost effectiveness	2 losses to follow up/withdrawals, reasons given Analysed by intention to treat
Walker 1997 USA	19 married sexually active women aged 28-44 with hx of recurrent UTI	Cranberry capsules (400 mg of cranberry solids): daily dose not stated vs placebo capsule		·      Symptomatic UTI	47% lost to follow up/withdrew (9/19), reasons given

 

Summary details of the trial published since publication of the Cochrane review are as follows:

Study	Participants	Intervention/Comparison	Outcomes measured	Comment
McMurdo 2005	376 hospital patients aged ³60 yrs	150 mls cranberry juice (25% cranberry concentrate) vs placebo beverage that looked and tasted identical twice daily for 35 days or until discharge from hospital	Time to onset of symptomaticUTI, Antibiotic use Adverse events	RCT Double blinded Study failed to meet recruitment target of 440 participants and incidence of UTI was low, further reducing study power 30% loss to follow up/withdrawals - reasons given   Median observation time was 22-23 days

Three RCTs were excluded. Two of these trials evaluated cranberry juice for the treatment as opposed to the the prevention of UTI (Waites 2004, Linsenmeyer 2004). The third enrolled children at daycare centres and measured the incidence of any infection; these children were not at high risk of UTI and UTIs were so rare that no comparison could be made between the groups (Kontiokari 2005). 

9. Methodological quality
The included studies were evaluated using the SIGN criteria.

The Cochrane review (Jepson 2004) was of good quality. However, four out of seven of the individual trials included in the review were of questionable quality with very high (over 45%) losses to follow up (Foda 1995, Haverkorn 1994, Walker 1997) or a poor standard of reporting (Avorn 1994). Only two of the studies in this review were suitable for meta-analysis (Kontiokari 2001, Stothers 2002).

 The primary study published since the systematic review (McMurdo 2005) was fair quality, but had a 30% rate of withdrawals and losses to follow up. This trial was statistically underpowered, partly because it did not meet the target for enrolment and partly because the incidence of UTI among the older hospital patients enrolled was lower than anticipated.

10. Results

Effectiveness for preventing UTIs

In the systematic review, two good quality RCTs (Kontiokari 2001; Stothers 2002) were pooled. These trials compared cranberry products (capsules and juice) with placebo or control capsules/drinks in women with recurrent urinary tract infections. Symptomatic UTIs were significantly less likely to recur over one year follow-up among women taking cranberry products (risk ratio 0.61, 95% confidence interval 0.40 to 0.91). Both these trials were analysed by intention to treat.

Among the other five trials in the systematic review, two reported statistically significant results favouring the use of cranberry for preventing recurrence of symptomatic UTI (Walker 1997) and for reducing the incidence of high urinary bacteria counts (Avorn 1997). However, as noted above, these trials were of low quality. No statistically significant benefit was shown for cranberry in the other trials.

The trial published since the systematic review (McMurdo 2005) found no statistically significant difference between the two groups in the incidence of symptomatic urinary tract infections. The trial was probably underpowered to find a difference. There were 7/187 infections (3.7%) in the cranberry group and 14/189 (7.4%) in the placebo group.

 Adverse events

The authors of the systematic review speculated that the high rate of losses to follow up in the included trials might indicate that cranberry juice is not acceptable over long periods. However, only one of the trials that systematically measured adverse events reported a higher rate in the cranberry group; in this trial of 40 children, 17/19 withdrawals occurred during treatment with cranberry, and twelve withdrawals were due to adverse events, namely taste (9/40), caloric load (2/40) and cost (1/40) (Foda 1995).

The additional trial published since the systematic review found no statistically significant difference between the cranberry juice group and the placebo drink group in the incidence of adverse events (3–4% in each group), nor in the number of participants withdrawing because they disliked the beverage (6% in the placebo group, 4% in the cranberry group).

Cost of treatment

One trial reported on the cost of using cranberry to prevent UTIs (Stothers 2002). Costs were over twice as high for juice as for tablets. Cost effectiveness was highest when people experienced more than two symptomatic UTIs per year (assuming three days of antibiotic coverage) and had more than two days of missed work or required protective undergarments for urgency incontinence.

Summary of results for the outcome Recurrent urinary tract infection

Study	Sample size	Comparison	Relative risk (95% confidence interval)
Jepson 2004	Two RCTS pooled n = 251 total	Cranberry products vs placebo/control	0.61 (0.40 to 0.91)

11. Discussion of Findings
The Cochrane systematic review (Jepson 2004) found evidence that cranberry juice decreased the number of symptomatic UTIs over a 12-month period in women with a histroy of recurrent UTI. However, the effectiveness of cranberry products for other groups, such as children, older men and women, was unclear. Moreover, the optimum dosage and method of administration (eg, juice or tablets) was also unclear, with treatments differing widely between trials.

A more recent trial (McMurdo 2005) was underpowered and inconclusive as to the effectiveness of cranberry for preventing UTI in older people in hospitals. This trial found that cranberry juice was acceptable for older hospital patients, and there was a similar rate (4–6%) of adverse events in both cranberry and placebo groups.

There was no consistent evidence in these studies of any adverse events associated with cranberries, but the trials were probably underpowered to adequately assess adverse events. A report from the UK’s Committee on Safety of Medicines in 2003 suggested, based on a series of case reports, that cranberry might interact with warfarin medications, preventing their effectiveness. Until this possible interaction between cranberry juice and warfarin has been investigated further, patients taking warfarin should limit their intake of cranberry or avoid taking it (Suvarna 2003).

12. Conclusions
There is level one evidence from meta-analysis of two RCTs included in the systematic review (Jepson 2004) that cranberry juice decreases the risk of recurrent urinary tract infection in women with a history of UTI. The effectiveness of cranberry products for preventing UTI in other groups is unclear.

There was no consistent evidence in these studies of any adverse events associated with cranberries, although one small trial reported that 23 per cent of children (9/40) could not tolerate the taste. There is level two evidence from a recent RCT (McMurdo 2005) that cranberry juice is well accepted and tolerated by older people. However, in view of reports of an interraction between warfarin and cranberry products, people taking warfarin should be cautious in using cranberries.

There is no evidence as to what form of cranberry treatment is most effective, what dose is optimum or how long it should be taken for.

13. References

Avorn J, Monane M, Gurwitz J, Glynn R. Reduction of bacteriuria and pyuria with cranberry beverage: a randomized trial. Journal of the American Geriatrics Society 1993;41(10 Suppl):13.

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

Foda MM, Middlebrook PF, Gatfield CT, Potvin G, Wells G, Schillinger JF. Efficacy of cranberry in prevention of urinary tract infection in a susceptible pediatric population. Canadian Journal of Urology 1995;2(1):98-102.

Haverkorn MJ, Mandigers J. Reduction of bacteriuria and pyuria using cranberry juice [letter]. JAMA 1994;272(8):590.

Jepson 2004. Cranberries for preventing urinary tract infections (full Cochrane review):
http://www.mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD001321/frame.html

Kelly J. Clinical syndromes of urinary tract infection. Current Therapeutic Research 1977;38(7):15-21.

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):1571–3.

Kontiokari T, Salo J, Eerola E, Uhari M. Cranberry juice and bacterial colonization in children - A placebo-controlled randomized trial. Clinical Nutrition 2005;24: 1065-72.

Linsenmeyer TA, Harrison B, Oakley A, Kirshblum S, Stock JA, Millis SR. Evaluation of cranberry supplement for reduction of urinary tract infections in individuals with neurogenic bladders secondary to spinal cord injury. Journal of Spinal Cord Medicine 2004; 27(1): 29-34.

McMurdo MET, Bissett LY, Price RJG, Phillips G. Does ingestion of cranberry juice reduce symptomatic urinary tract infections in older people in hospital? A double-blind, placebo-controlled trial. Age and Ageing 2005; 34:256-61.

Roberts AP, Phillips R. Bacteria causing symptomatic urinary tract infection or asymptomatic bacteriuria. Journal of Clinical Pathology 1979;32(5):492-6

Schlager TA, Anderson S, Trudell J, Hendley JO. Effect of cranberry juice on bacteriuria in children with neurogenic bladder receiving intermittent catheterization. Journal of Pediatrics 1999;135(6):698-702.

Stamm WE, Hooton TM. Management of urinary tract infections in adults. New England Journal of Medicine 1993;329: 1328-34

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):1558-62.

Suvarna R, Pirmohamed M, Henderson L. Possible interraction between warfarin and cranberry juice. BMJ 2003; 327: 1454.

Waites KB, Canupp KC, Armstrong S, DeVivo MJ. 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.

Walker EB, Barney DP, Mickelsen JN, Walton RJ, Mickelsen RA Jr. Cranberry concentrate: UTI prophylaxis [letter]. Journal of Family Practice 1997;45(2):167-8.

Wong ES, Fennell Cl, Stamm WE. Urinary tract infection among women attending a clinic for sexually transmitted diseases. Sexually Transmitted Diseases 1984;11(1):18-23

Zafriri D, Ofek I, Adar R, Pocino M, Sharon N. Inhibitory activity of cranberry juice on adherence of type 1 and type P fimbriated E. coli to eucaryotic cells. Antimicrobial Agents & Chemotherapy 1989;33(1):92-8.

 

Date report prepared: 27 Jan 2006                                                     Last updated: 7 Feb 2006

 

 

 

 

 

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