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Mar 11

Cranberry juice fails for urinary tract infections

Journal reference: Barbosa-Cesnik C, Brown MB, Buxton M, et al. Cranberry juice fails to prevent recurrent urinary tract infection: results from a randomised placebo-controlled trial. Clinical Infectious Diseases. 2011; 52(1): 23-30 [1]

Link: http://dx.doi.org/10.1093/cid/ciq073

Published: 1 January 2011

Evidence cookie says...

Cranberry juice is not associated with a lower incidence of UTI recurrence than placebo juice in young, sexually active college women.

This was a well conducted randomised controlled trial and provides moderate-high level evidence.

Prior studies supporting the use of cranberry offered only low/low-moderate level evidence.

Cranberry products are likely to be safe but come at substantial cost to the individual consumer. Australian general practitioners should not recommend or promote cranberry as an effective therapy for the prevention of urinary tract infections.

More details:


Article details


Study design:

double-blind randomised controlled trial


Study aim:

to determine the effect of drinking cranberry juice regularly on rate of recurrence of urinary tract infection (UTI) compared with placebo juice


Methods summary:

  • August 2005 to October 2007
  • consenting women presenting for urinalysis at the University of Michigan Health Service Laboratory
  • inclusion criteria:
    • aged 18-40 years
    • ≥ 3 urinary symptoms
    • would be in Ann Arbor for the following 6 months
  • exclusion criteria:
    • antibiotic treatment in the previous 48 hours
    • hospitalisation or catheterisation within the previous 2 weeks
    • kidney stones
    • diabetes
    • pregnancy
    • cranberry allergy
    • negative urine culture result
  • confirmation of UTI based on culture results
  • treatment of index UTI with antibiotics deemed adequate by their treating physicians
  • follow up for 6 months or first confirmed UTI, whichever was first
  • randomisation to either:
    • cranberry juice:
      • 8 oz (237 mL) of 27% low calorie cranberry juice cocktail (LCJC)
      • formulated to be similar to the commercially available Ocean Spray LCJC, the cranberry juice was provided by Ocean Spray Cranberries
      • standarised for proanthocyanidin content → mean 112 mg per dose
      • twice daily for 6 months
    • placebo control:
      • 8 oz (237 mL) of placebo juice twice daily
      • also formulated by Ocean Spray to imitate the flavour (sugar and acidity) and colour of cranberry juice without any cranberry content
      • taken twice daily for 6 months
  • regular follow up at 3 and 6 month visits with urinary culture analysis as well as interim urinary culture analysis if symptoms occurred
  • questionnaires about urinary symptoms, and risk behaviours
  • laboratory analysis of urine for uropathogens; similar repeated isolates were tested to distinguish treatment failure versus recurrence with different strain

Primary endpoint:

  • confirmed urinary tract infection

Analysis:

  • randomisation by a biometrics and research unit at the University of Michigan
  • participants, investigators and their staff remained blinded to treatment allocation until the end of the trial
  • power calculations made a priori
    • 120 subjects per group
    • 80% power to detect a 2-fold difference between the treatment and placebo groups (detected in unblinded trials)
    • assumption that 30% of participants would experience a UTI during the follow up period
  • intention to treat analysis

Results summary:

  • 1507 women screened
    • 269 unwilling to participate
    • 818 not eligible
    • of 419 enrolled and eligible → 319 had positive urine cultures
  • 319 participants underwent randomisation
    • 155 to cranberry juice and 164 to placebo beverage
    • 72% completed the entire protocol
      • drop out rates similar between the two study groups

Primary outcome:

  • overall recurrence rate: 16.9 %
    • note: less than the predicted 30%
    • cranberry juice group: 19.3%
    • placebo group: 14.6%
    • log-rank test: P = 0.21
  • no difference in risk of recurrence after adjusting for sexual activity and previous UTIs

Study conclusion:

Drinking twice daily cranberry juice fails to prevent recurrent UTIs in healthy college women.


Participants:

  • August 2005 to October 2007
  • population of American college women aged 18-40 years, otherwise healthy, sexually active and most with history of prior UTIs
  • all had culture confirmed UTI at enrolment
  • notable exclusions:
    • kidney stones
    • diabetes
    • pregnancy
  • Baseline participant characteristics:
    • mean age: 21.2 years, SD = 3.4
    • mean UTIs in past 12 months: 1.30
    • mean frequency of vaginal intercourse in previous 4 weeks: 10.1
    • oral contraceptives: 75.2%
    • ethnicity:
      • Hispanic: 6.0%
      • White: 73.3%
      • Black: 6.9%
      • Asian: 16.0%

Methodological weaknesses

  • placebo juice contained ascorbic acid (vitamin C) which has been suggested possess antibacterial activity in a previous study [2]
    • Morsel of Evidence author’s note:
      • the distribution of organisms of recurrent UTI appeared to be different between cranberry and placebo groups
      • E. coli comprised 95% of cranberry group versus 58.3% of placebo group
      • speculation: perhaps there is a specific antibacterial activity in the ascorbic acid contained in placebo that is effective against E. coli in particular, but less so against other uropathogens
  • study design assumed a 30% rate of UTI recurrence but only a rate of 16.9% was observed
    • the lower rate reduced the power of the study and it may have masked a real difference between two groups
  • compliance with regular drinking of juice was based upon self reporting in both groups

Methodological strengths

  • attempts made to formulate placebo juice in similar way to cranberry juice
  • standardisation of presumed active ingredient (proanthocyanidin)
  • well conducted study with good blinding and randomisation procedure
  • good representation of different ethnicities in the participants

Biases and conflicts of interests

  • none declared
  • study was funded by grant from National Centre for Alternative Medicine at NIH

Clinical relevance to primary health care

Urinary tract infections (UTIs) are the most commonly seen bacterial infections seen the primary health care setting. The incidence is highest among young sexually active women. Cranberry is a traditional remedy used to prevent UTI. Encouraging results from observation studies and small randomised trials have led to the widespread use and promotion of cranberry as a preventative agent against recurrent urinary tract infections.

This well conducted trial does not demonstrate any beneficial association between the use of cranberry juice and the incidence of UTI recurrence, compared to placebo juice.

This trial was possibly underpowered given the lower than expected incidence of UTI recurrence and dropouts. However, there was no trend favouring the cranberry group; indeed, it had a higher cumulative incidence of UTI recurrence. The study design, formulation of the placebo juice, randomisation and blinding all served to minimise the likelihood of bias.

If there is an active component to cranberry juice, it might be that it is not unique to cranberry. Both the cranberry juice and placebo juice contained ascorbic acid (vitamin C). This has been suggested to prevent UTIs but has never been demonstrated to reduce risk in controlled trials. Another speculation and possible hypothesis is that the lower than expected rate of UTIs was simply due to the participants being better hydrated.

There was prior low level evidence suggesting efficacy of cranberry in the prevention of UTIs. This study provides moderate-high level evidence (NHMRC Level II) that cranberry is ineffective in young sexually active women who were otherwise well.

Although cranberry products are likely to be safe, regular cranberry juice and capsules come at substantial cost to the individual consumer. Australian general practitioners should not recommend or promote cranberry as an effective therapy for the prevention of urinary tract infections.

References

  1. Barbosa-Cesnik C, Brown MB, Buxton M, et al. Cranberry juice fails to prevent recurrent urinary tract infection: results from a randomised placebo-controlled trial. Clinical Infectious Diseases. 2011; 52(1): 23-30
  2. Carlsson S, Wiklund NP, Engstrand L, et al. Effects of pH,nitrite, and ascorbic acid on nonenzymatic nitric oxide generation and bacterial growth in urine. Nitric Oxide 2001; 5:580–586.

Editor: Michael Tam

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1 comment

  1. avatar
    Michael Tam

    I now have a regular column, Examining the Evidence in Medical Observer, a weekly general practice news magazine. My first article was published on 16 August 2011, “Can cranbery prevent UTIs?“. The simplified critical appraisal was on this article.

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