Tuesday July 26 2011
The Daily Telegraph reported that, “women who drink cranberry juice to ease urinary tract infections would be better off sticking to a low dose of antibiotics.”
The news coverage is based on a trial of whether cranberry tablets are ‘as good as’ at preventing urinary tract infections (UTIs) in premenopausal women who are prone to recurrent infections. Women with recurrent UTI (three or more in a year) are often given antibiotics as a preventative.
This 12-month study found that, compared to antibiotics, cranberry tablets were of no benefit at preventing UTIs in these women. The study had some limitations, including a high drop out rate, and so doesn’t represent the last word in whether cranberry juice can help in this way.
Importantly, this study did not assess whether cranberries have a preventative effect relative to no treatment. A Cochrane Systematic Review found that cranberry products reduced the recurrence of UTIs after 12 months treatment compared to placebo. However, like the current study, it found that the trials had a large number of participants that dropped out and that the optimum dose was not known.
Further research to see whether there is an optimum dose of cranberry to prevent UTIs is warranted. Taking preventative antibiotics is not ideal, and can lead to antibiotic resistance occurring. This study highlights the need for continued research for new non-antibiotic treatments for recurrent UTIs.
Where did the story come from?
The research was conducted by researchers from various medical centres in The Netherlands. The study was funded by the Netherlands Organisation for Health Research and Development and was published in the peer reviewed medical journal Archives of Internal Medicine.
The Daily Telegraph report does not say that this was a preventative treatment for women who were prone to recurrent UTIs. Although it mentions that cranberry capsules were used in the article, the top section implies that cranberry juice was assessed for treatment of active infections, which was not the case.
What kind of research was this?
The aim of this study was to compare the effectiveness of antibiotics to cranberry extract at preventing UTIs in a group of premenopausal women who were prone to getting them.
This was a ‘non-inferiority trial’, meaning that it tested whether a new treatment (in this case the cranberry extract) is equivalent to an existing standard treatment (trimethoprim-sulfamethazole (TMP-SMX). TMP-SMX is a standard antibiotic used in the treatment of UTIs.
The participants, who all had at least three infections over one year, were given either the extract or the antibiotic for 12 months.
The researchers said that for premenopausal women who have three or more UTIs a year, low-dose preventative antibiotics are usually recommended. However, this has the risk of leading to drug resistance not only of the bacteria that cause the infection but also the normal bacteria that live in that area. Therefore, alternative methods are needed.
Cranberries have been used for the prevention of UTIs for many years but it has not been established how they work. The researchers therefore wanted to see whether a cranberry tablet would prevent UTIs to a similar extent to antibiotics.
Women are, in general, at higher risk of UTIs compared to men. This is due to the short urethra and the close proximity of the urethral opening to the anus (which can allow transfer of bacteria such as E. coli from the digestive tract). Activities such as sexual intercourse can increase the likelihood of bacterial transfer.
What did the research involve?
The researchers recruited 221 premenopausal women who were over 18 years of age, who had self-reported at least three symptomatic UTIs in the past year. The women were from the Netherlands and were recruited between January 2005 and August 2007. The study excluded women who had a UTI at the time of enrolment or who had taken antibiotics or cranberries in the past two weeks.
Women with allergies to the TMP-SMX antibiotic were excluded, as were women taking oral anticoagulants or those who had renal stones as taking cranberries may be contraindicated in these women. The study also excluded women who were pregnant or planning pregnancy, breastfeeding or had previously had a kidney transplant.
The women were randomised to either receive for 12 months:
- One tablet with 480mg TMP-SMX at night, and one placebo capsule twice daily (110 women)
- One capsule with 500mg cranberry extract (Cran-Max, Proprietary Nutritionals Inc, Kearny, New Jersey) twice daily, and one placebo capsule at night (111 women)
Neither the participants nor the researchers knew which tablets the participants were taking. The participants were told not to use any other antibiotic or cranberry treatment alongside their study treatment for the course of the study.
The researchers collected demographic and clinical characteristics of the women at enrolment. The women were asked to collect a urine and faeces sample (to assess E Coli) just before starting the study treatments. They did this once a month for the 12-month test period and for another three months after they had stopped taking the study medication. During these times the women were also asked about any UTI symptoms, side effects, infections other than UTIs or whether they had taken antibiotics for any reason.
After 12 months (or earlier if women dropped out of the study) they were asked to guess which treatment they had received.
The researchers assessed the bacterial composition of the samples, the number of recurrences of UTIs the women experienced and whether the E. coli bacteria in the samples were resistant to TMP-SMX.
What were the basic results?
The researchers found that after 12 months, the cranberry group experienced on average more symptomatic UTIs than the TMP-SMX group. On average there were four infections in the cranberry group [95% confidence interval CI 2.3 to 5.6] compared to 1.8 in the antibiotics group [95% CI 0.8 to 2.7]).
The cranberry group also had a higher proportion of women who had experienced at least one symptomatic UTI (78.2% versus 71.1% in the antibiotic group). Women in the cranberry group had their first recurrence on average four months after starting treatment compared to eight months with the antibiotic group.
However, after one month of using TMP-SMX, resistance to this antibiotic had increased from around 21.1% - 27.8% to 72.5% - 90.5% in both the faeces and the urine samples. Three months after stopping treatment, the bacterial resistance had returned to the same levels as before treatment had started. Antibiotic resistance did not increase in the cranberry group.
In both groups, many people did not complete follow-up to 12 months. In the TMP-SMX group, only 57 out of 110 reached their 12-month assessment. In the cranberry group, 53 out of 111 had follow-up at 12 months. Reasons for not completing the study included, lack of efficiency of the treatment leading to withdrawal, burden of the study leading to withdrawal, and adverse events or losing participants to follow-up.
Cranberries and TMP-SMX were equally well tolerated with similar levels of mild adverse effects. At the end of the study the participants were not able to guess which treatment they had been on.
How did the researchers interpret the results?
The researchers said, ‘in premenopausal women, TMP-SMX, 480 mg once daily, is more effective than cranberry capsules, 500mg twice daily to prevent recurrent UTIs, at the expense of emerging antibiotic resistance’.
This was a well-conducted trial designed to see whether cranberry tablets were ‘as good as’ preventative antibiotic tablets at preventing recurrent UTIs in premenopausal women who were prone to UTI recurrence. Although the study showed that antibiotic treatments were more effective, it also found that antibiotic resistance became more prevalent in women taking them.
UTIs are common in women, and a single UTI is usually treated by a one-off three-day course of antibiotics. This study was specifically investigating women with recurrent UTI, which is usually defined as a woman who has three or more UTIs in one year. Such women are at higher risk of regular infections and they may be given preventative antibiotics. Therefore, no assumptions should be made from this study about the effect of cranberry tablets and antibiotics at treating UTIs in women who are not prone to recurrence in the general population.
There were high withdrawal rates in both groups, and any long-term preventative treatment needs people to keep on taking it. The researchers said that in the cranberry group, women experiencing higher recurrence were more likely to drop out, but that they had adjusted for these in the analysis. They also pointed out that they did not check whether people had taken the tablets, which may have meant that people did not take the complete course of treatment.
This study found that cranberry tablets (at that dose) were not beneficial compared to antibiotics for preventing UTI infections. However, taking prophylactic antibiotics is not ideal as this may lead to antibiotic resistance occurring. This study highlights the need for continued research for new non-antibiotic treatments for recurrent UTIs.
This study did not look at the effect of taking cranberry tablets compared to no treatment and it is not possible to say that cranberry products have no benefit based on this trial. A Cochrane review (updated in 2007) found that cranberry products taken as a preventative treatment reduced the recurrence of UTIs after 12 months treatment compared to placebo, but like the current study found that the trials had a large number of participants that dropped out. It was noted in the Cochrane review and the current study that the optimum dose of cranberry for the prevention of UTIs is not clear. A second Cochrane review (updated in 2010) assessed the evidence for cranberries to treat an active UTI, and the researchers concluded that there were a lack of published randomised controlled trials and so it was not possible to determine the effect of cranberries to treat UTIs.
Women are at higher risk of UTIs than men due to the short urethra and the close proximity of the urethral opening to the anus. Women who are experiencing regular UTIs should always consult their doctor.
Ways for all women to help prevent UTIs include:
- drinking plenty of water
- always urinating whenever you feel the need (not holding on)
- wiping front to back (to avoid transfer of bacteria from the anus to the urethra)
- avoiding using heavily scented shower gels or soaps or feminine hygiene sprays
- Activities such as sexual intercourse can increase the likelihood of bacterial transfer, and washing the genital area prior to having sex, or emptying the bladder after sex may help