The following is the first article in a new two-monthly column published in Medical Observer, an Australian non-peer reviewed news/periodical for general practitioners.
It is on the Medical Observer website (may need registration).
Debbie, a woman in her early 30s saw me the other day. She smiled but appeared a shade uncomfortable in the consulting room, “Michael, I think I have another bladder infection”. She had typical symptoms, dipstick urinalysis demonstrated blood and nitrites. Her last UTI was 2 years ago. As we were finishing the consultation, Debbie asked, “Should I be taking cranberry juice?”
Does drinking cranberry juice reduce the frequency of UTIs in young women?
There is a widespread popular belief that cranberry juice is effective in the prevention of UTIs. If Debbie consulted “Dr Google” she would discover that a government website1 and a women’s magazine2 suggest that cranberry juice can prevent UTIs.
But what does the research evidence say?
Step 1: The Cochrane Library
A good first step is The Cochrane Library. Does a high-quality systematic review exist? Searching for the term “cranberry” reveals a hit, however, the conclusion suggests weakness in the evidence base (in 2008)3:
“There is some evidence that cranberry juice may decrease the number of symptomatic UTIs over a 12 month period… the large number of dropouts/withdrawals indicates that cranberry juice may not be acceptable over long periods of time… not clear what is the optimum dosage or method of administration… further properly designed studies with relevant outcomes are needed.”
Step 2: Pubmed
The second step is PubMed. Are there any new randomised controlled trials? I used the search strategy:
(cranberry juice) AND urinary tract infection; limited to randomised controlled trials, English language, and published since 2008 only
Five results! The first study seems very promising; a double-blind placebo-controlled trial on the effects of cranberry on recurrence of UTI in college women4. Let’s look at that study (Barbosa-Cesnik, et al. 2011) in detail.
It is tempting to jump straight to the results and conclusion. However, if the method is flawed, then the results may be misleading. Rather we should focus on methods first, and then results5. I use the critical appraisal sheets available from the Centre for Evidence Based Medicine website.
Participants: who was studied?
American college women, mean age 21 years, who presented with symptoms of UTI that was confirmed on urine culture. They were healthy, had a history of previous UTIs, sexually active, and 75% were on the pill. Notable exclusions: kidney stones, diabetes and pregnancy.
Intervention: what was the exposure?
8 oz (237 mL) of a cranberry juice cocktail twice daily, for 6 months, formulated to have a proanthocyanidin content of 112 mg per dose, and similar to “Ocean Spray”.
Comparator: what was the control/alternative?
Placebo juice imitated the colour and flavour of “Ocean Spray” without any cranberry content.
Outcomes: what was measured?
The primary endpoint was a confirmed urinary tract infection.
Internal validity: are the trial results valid?
Was the assignment of patients to treatment randomised?
Were the groups similar at the start of the trial?
Yes. There were no substantial difference between the two groups (Table 1, page 27)4.
Aside from the allocated treatment, were the groups treated equally?
Were all patients who entered the trial accounted for?
Yes. There were similar dropout rates and analyses were performed on intention to treat basis.
Were measures objective or were the patients and clinicians kept blind to which treatment was received?
Yes. Both the investigators and the participants were blinded to the allocation of juice.
What were the results?
The overall UTI recurrence rate at 6 months was 16.9%. No benefit was associated with cranberry; the intervention group had a higher recurrence rate (19.3%) compared to the placebo group (14.6%). The result was not statistically significant.
Questions to consider when deciding if these results help you care for your patients6:
- Is my patient so different to those in the study that the results cannot apply?
- Is the treatment feasible in my setting?
- Will the potential benefits of treatment outweigh the potential harms of treatment for my patient?
There is moderately-high level evidence that cranberry juice is ineffective in the prevention of UTIs in young sexually-active women, as compared to placebo juice. The overall recurrence rate of UTIs in above study was lower than expected and speculatively, it might be that the active ingredient is simply water7.
The results from the above study seem to apply to Debbie. So, in reply to Debbie’s question, it is unlikely that cranberry juice is harmful but also unlikely that it will be beneficial for the prevention of UTIs.
Practical EBM for GPs (adapted from the “five basic tenets”8)
- Best available scientific evidence should guide clinical decisions
- Generate answerable questions to clinical problems you encounter
- Seek the best evidence to your questions
- Put the evidence into action for your patients
- Evaluate your performance
- The Cochrane Library: http://www.thecochranelibrary.com
- PubMed: http://www.ncbi.nlm.nih.gov/pubmed
- Centre For Evidence Based Medicine; Critical Appraisal: http://www.cebm.net/index.aspx?o=1157
RCTs are a type of scientific experiment. Compared to other research designs, they provide the strongest evidence for concluding causation, that the result was the result of the intervention9. As the participants meeting entry criteria are randomised to the treatment groups, it reduces the likelihood of selection bias and confounding.
- Urinary tract infections. Better Health Channel [website]. Retrieved on 9 July 2011. http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/urinary_tract_infections
- Pan C. GP’s view: UTIs. Body+soul [website]. Retrieved on 9 July 2011. http://www.bodyandsoul.com.au/health+healing/expert+opinion/gps+view+utis,8657
- Jepson RG, Craig JC. Cranberries for preventing urinary tract infections. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD001321. DOI: 10.1002/14651858.CD001321.pub4
- 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
- Montori VM, Jaeschke R, Schünemann HJ, et al. Users’ guide to detecting misleading claims in clinical research reports. BMJ 329: 1093
- RCT Appraisal Sheets. Centre For Evidence Based Medicine [website]. Retrieved on 9 July 2011. http://www.cebm.net/index.aspx?o=1097
- Beetz R. Mild dehydration: a risk factor for urinary tract infection. European Journal of Clinical Nutrition 2007; 57, Suppl 2: S52-58
- Jacobson LD, Edwards AGK, Granier SK, Butler CC. Evidence-based medicine and general practice. British Journal of General Practice 1997; 47: 449-52
- Dawson B, Trapp RG. Study designs in medical research (Ch 2) in Basic & Clinical Biostatistics, 4th edition. The McGraw-Hill Companies. 2004