Article on UTI and Cranberry Products

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From Medscape Education Clinical

Briefs<http://www.medscape.org/index/list_968_0>Protection

Against Urinary Tract Infections Seen With Cranberry Products CME/CE

News Author: Troy Brown

CME Author: Désirée Lie, MD, MSEd

Faculty and Disclosures<http://www.medscape.org/viewarticle/767190?src=cmemp>

CME/CE Released: 07/11/2012; Valid for credit through 07/11/2013

CME/CE Information <http://www.medscape.org/viewarticle/767190?src=cmemp> Earn

CME/CE Credit »<http://www.medscape.org/qna/processor/25609?showStandAlone=true>

CLINICAL CONTEXT

According to the current study by Wang and colleagues, urinary tract

infection (UTI) is one of the most commonly acquired bacterial infections,

and cranberry-containing products have long been used as a folk remedy to

prevent UTIs. Up to 40% to 50% of women will experience at least 1 episode

of UTI during their lifetimes. Approximately 20% to 30% of women who have

had an infection will experience a recurrence. Other groups with an

increased risk for UTI include pregnant women, elderly patients, and

patients with neuropathic bladder.

This systematic review and meta-analysis of randomized controlled trials

determines the efficacy of cranberry products in the prevention of UTIs.

STUDY SYNOPSIS AND PERSPECTIVE

Cranberry-containing products may protect against UTIs, according to a recent

meta-analysis<http://archinte.jamanetwork.com/article.aspx?articleid=1213845>.

However, because there was substantial heterogeneity among the studies, the

results of the analysis should be viewed with caution, the researchers say.

Chih-Hung Wang, MD, from the Department of Emergency Medicine at National

Taiwan University Hospital and National Taiwan University College of

Medicine in Taipei and colleagues report their findings in the July 9 issue

of the*Archives of Internal Medicine*.

One of the most common bacterial infections, UTIs affect up to 40% to 50%

of women at least once in their lifetimes, the authors report. Pregnant

women, the elderly, and patients with neuropathic bladder are also at

increased risk for developing UTIs.

Cranberry (genus *Vaccinium*, including the species *V oxycoccus, V

macrocarpon, V microcarpum*, and *V erythrocarpum*) is a folk remedy that

has been used for years to relieve UTI symptoms. Cranberry was originally

thought to work by acidifying the urine, but its effects are now known to

be due to its interference with the attachment of bacteria to uroepithelial

cells. In fact, A-type proanthocyanidins were identified in cranberry in

1989 as compounds with the potential to inhibit the adherence of

P-fimbriated *Escherichia coli* to the urogenital mucosa.

Several new studies have been published since the last meta-analysis on

this issue. Therefore, Dr. Wang and his team wanted to reevaluate the

effectiveness of cranberry products for preventing UTIs and to study

factors that influence their effectiveness.

Dr. Wang and colleagues analyzed 10 trials with a total of 1494

participants (794 in the cranberry groups and 700 in the control groups) in

the meta-analysis. Significant heterogeneity was found among trials

(relative risk [RR], 0.68; 95% confidence interval [CI], 0.47 - 1.00; *I* *2

* = 59%). One trial was excluded from the main analysis because it had the

most significant effect on the pooled summary estimate.

*Cranberry Products Appear Effective*

Heterogeneity decreased after exclusion of this trial, and

cranberry-containing products appeared to effectively prevent UTIs (RR,

0.62; 95% CI, 0.49 - 0.80; *I* *2* = 43%).

According to sensitivity analysis, the pooled summary estimate was stable

to risks of bias in random sequence generation, study characteristics, and

definitions of UTI, but the protective effect was much stronger in 2

studies that did not use placebo in the control group (pooled RR, 0.36; 95%

CI, 0.21 - 0.62).

*Certain Populations Seem to Benefit More*

Subgroup analysis found that some populations seemed to experience higher

protective effects, including women with recurrent UTIs (RR, 0.53; 95% CI,

0.33 - 0.83; *I* *2* = 0%), female populations (RR, 0.49; 95% CI, 0.34 -

0.73; *I* *2* = 34%), children (RR, 0.33; 95% CI, 0.16 - 0.69; *I* *2* =

0%), cranberry juice users (RR, 0.47; 95% CI, 0.30 - 0.72; *I* *2* = 2%),

and people using cranberry-containing products more than twice daily (RR,

0.58; 95% CI, 0.40 - 0.84; *I* *2* = 18%). The findings, though, were not

statistically significant in meta-regression.

Cranberry juice was more effective than cranberry capsules. The authors

write that this could be due to increased hydration from drinking the juice

or the effects of unknown substances in the juice. The authors acknowledge

that drinking large quantities of juice could be problematic for some

individuals, including patients with diabetes and those with

gastrointestinal issues.

A dosing frequency of more than twice daily was more effective. " Because in

vitro data have suggested that the antiadhesion activity of cranberry juice

on fimbriated *E coli* lasts for approximately 8 hours after ingestion,

dosing more frequently than twice daily may be a reasonable choice, " write

the authors.

*Caution Needed*

" [T]he results of the present meta-analysis support that consumption of

cranberry-containing products may protect against UTIs in certain

populations. However, because of the substantial heterogeneity across

trials, this conclusion should be interpreted with great caution, " the

authors conclude.

*The authors have disclosed no relevant financial relationships.*

*Arch Intern Med*.

2012;172:988-996<http://archinte.jamanetwork.com/article.aspx?articleid=1213845>

..

STUDY HIGHLIGHTS

- The investigators systematically searched MEDLINE, EMBASE, and the

Cochrane Central Register of Controlled Trials from inception to November

2011 for randomized controlled trials that compared prevention of UTIs in

users of cranberry-containing products vs placebo or nonplacebo controls.

- There were no restrictions for language, population, or publication

year.

- 2 authors independently scanned the titles and abstracts of all

retrieved manuscripts to identify those pertinent to the review.

- Excluded were abstracts from conferences, proceedings, or clinical

trial registries.

- The investigators also manually searched bibliographies of relevant

studies, reviews, and meta-analyses to identify references that may have

been missed in the primary search.

- Prespecified inclusion criteria were randomized controlled trials,

comparison of cranberry-containing products vs placebo or nonplacebo

control for prevention of UTI, and outcomes reported as incidence of UTIs.

- The primary outcome was prespecified as the incidence of UTI, which

was expressed as either incidence or cumulative incidence rate, depending

on the original data.

- The Cochrane risk for bias tool was adopted to assess the risk for

bias for each trial, which was scored as " high risk, " " low risk, " or

" unclear. "

- 13 studies were identified as eligible for qualitative analysis, and

there were 9 parallel-group and 4 crossover trials.

- Of the 13 trials, 10 were performed in North America and 3 in Europe.

- All but 1 of the trials observed participants living in the community.

- Women with recurrent UTIs, elderly patients, patients with neuropathic

bladder, pregnant women, and children underwent further subgroup analysis.

- Administration of cranberry-containing products differed significantly

in form, daily dosage, A-type proanthocyanidin content, and dosing

frequency.

- 9 trials used cranberry juice, and 4 used cranberry capsules or

tablets.

- 6 trials used cranberry-containing products provided by a specific

manufacturer.

- Daily cranberry dose ranged from 0.4 to 194.4 g.

- In trials using daily cranberry amounts greater than 10 g, a huge

range of A-type proanthocyanidins, from 0.838 mg to 224 mg per day, was

reported.

- In contrast, those using daily cranberry amounts of less than 10 g did

not include information about A-type proanthocyanidin content.

- Cranberry-containing products were administered for 6 months in most

trials.

- 10 trials used a formulated placebo, 2 trials did not use a placebo,

and 1 trial used water as the placebo.

- 1494 participants across the 10 trials included in the quantitative

data synthesis, with 794 in the cranberry group and 700 in the control

group.

- There was significant heterogeneity among trials.

- The random-effects pooled RR for cranberry users vs nonusers was 0.62

(95% CI, 0.49 - 0.80), with a moderate degree of heterogeneity (*I* 2 =

43%) after the exclusion of 1 outlier study.

- A better preventive effect from cranberry-containing products was

noted with dosing frequency more than twice daily.

- Subgroup analysis showed that cranberry products seemed to be more

effective in women with recurrent UTIs (RR, 0.53; 95% CI, 0.33 - 0.83),

female populations (RR, 0.49; 95% CI, 0.34 - 0.73), children (RR, 0.33; 95%

CI, 0.16 - 0.69), cranberry juice users (RR, 0.47; 95% CI, 0.30 - 0.72),

and people using cranberry-containing products more than twice daily (RR,

0.58; 95% CI, 0.40 - 0.84).

- The authors concluded that cranberry-containing products were

associated with a protective effect against UTIs but that the result should

be interpreted in the context of substantial heterogeneity across trials.

CLINICAL IMPLICATIONS

- Use of cranberry products is associated with a reduction in the risk

for recurrent UTIs.

- The benefits of cranberry products for UTI prevention are greater in

women with recurrent UTI, female populations, children, those who drink

cranberry juice, and those who use the products more than twice daily.