Cranberry products in the prevention of urinary tract infections: examining the evidence

Figures & data

Table 1 Clinical trials on cranberry products for UTI prophylaxis

Study population/intervention/design	Result	Publication
Trials mainly in premenopausal women
Population: 150 young women (mean age 30 years) with previous UTI Intervention: randomization to drink 50 mL European cranberry/lingonberry concentrate daily for 6 months, or to drink 100 mL of a Lactobacillus drink 5 days per week for 12 months or no intervention Design: open design with first re-occurrence of symptomatic UTI as study end point	After 6 months, of the 150 women 16% of the cranberry-lingonberry group, 39% of the Lactobacillus, and 36% of the control group had a UTI recurrence. Drinking cranberry juice reduced the cumulative rate of the first re-occurrence of UTI by 56% vs control group and the absolute risk for UTI was reduced by 20%	Kontiokari et al^Citation45
Population: 176 premenopausal women with a recent history of UTI Intervention: cranberry juice 118 ml or 236 ml daily or placebo juice. The PAC content of cranberry juice is not known Design: double-blind placebo-controlled RCT over 6 months. Time to first recurrence of UTI (symptoms + pyuria) was the main outcome. Bacteriuria and bacterial adherence were monthly assessed	Occurrence of UTI in both cranberry groups not different from placebo. Reduction of urinary p-fimbriated Escherichia coli strains in cranberry groups	Stapleton et al^Citation38
Population: 319 college women (mean age 21 years) with a history of UTI Intervention: cranberry juice 236 ml twice daily or placebo juice. The PAC content of the cranberry juice is monitored to be around 1 12 mg per dose Design: double-blind placebo-controlled RCT over 6 months. End point UTI (symptoms + positive urine culture)	At a lower than expected recurrence rate of UTI (16%) there were no differences between the groups	Barbosa-Cesnik et al^Citation49
Population: 221 premenopausal women with recurrent UTI Intervention: cranberry capsules (500 mg twice daily – amount of A-type PAC 9.1 mg/g) or TMP-SMX (480 mg once daily) Design: double-blind double-dummy non-inferiority trial over 12 months with primary end points of number of symptomatic UTIs, proportion of patients with at least one UTI, time to first UTI and development of antibiotic resistance	More UTI in cranberry group (4 vs 1.8 in TMP-SMX) and median time to first UTI shorter (4 vs 8 months). Emerging antibiotic resistance in TMP-SMX group An economic evaluation carried out alongside with this trial found higher costs for the cranberry-treated patients without taking into account possible costs related to antibiotic resistance	Beerepoot et al^Citation40 and Bosmans et al^Citation41
Population: 150 sexually active women (aged 21-72 years) with history of UTI Intervention: consumption of American cranberry juice (250 mL three times per day) or tablets with cranberry extract (two times per day) for 1 year Design: double-blind, placebo-controlled, intent-to-treat design and cost-effectiveness analysis Randomization to three groups: placebo juice + placebo tablets vs placebo juice + cranberry tablets vs cranberry juice + placebo tablets. Outcome measures: >50% decrease in symptomatic UTI per year (symptoms + ≥ 100,000 organisms/mL) and >50% decrease of annual antibiotic consumption	Both, cranberry juice and tablets decreased the number of patients experiencing at least one symptomatic UTI/year (to 20% and 18%, respectively) compared with placebo (to 32%) (P<0.05). The mean annual cost was lower for tablets than for juice	Stothers^Citation53
Population: 1 18 patients 20-79 years old, with a history of UTI Intervention: intake of cranberry juice or a placebo beverage (125 mL) once daily before going to sleep Design: RCT double-blinded, over 24 weeks	Less recurrence of UTI with cranberry juice intake in the subgroup of women >50 years	Takahashi et al^Citation55
Population: 188 pregnant women Intervention: cranberry or placebo in three treatment arms of A-cranberry three times daily, B-cranberry at breakfast then placebo at lunch and dinner, and C-placebo three times daily. After 52 subjects were enrolled, the dosing frequency was reduced to twice daily because of a high withdrawal rate and poor tolerability of the thrice daily dosing regimen Design: randomized controlled trial	There was a 57% and 41 % reduction in the frequency of asymptomatic bacteriuria and UTI in the multiple daily dosing group. However, this study was not sufficiently powered at the alpha 0.05 level (Cl 0.14-1.39 and 0.22-1.60, respectively, incidence rate ratios). Of 188 subjects 73 (38.8%) withdrew, most for gastrointestinal upset	Wing et al^Citation59
Trials mainly in postmenopausal women
Population: 153 elderly postmenopausal women (mean age 78.5 years) Intervention: daily consumption of 300 mL standard cranberry beverage or placebo drink for 6 months Design: double-blind, placebo-controlled trial, no intent-to-treat design. Study groups were compared for the combined occurrence of bacteriuria and pyuria (= infected urine) in 818 urine samples collected at baseline and monthly during the study period	In the cranberry group, the odds for infected urine had been 42% of the odds of the control group. The difference was first detectable after 2 months. The odds for patients with infected urine to remain so was 27% of the control group. Patients in the cranberry group were far more likely to make the transition from infected to non-infected urine There was no acidification of urine by cranberry	Avorn et al^Citation56
Population: 137 older women with >2 UTI in the previous 12 months Intervention: cranberry extract (500 mg/day) or trimethoprim (100 mg/day). The PAC content of the cranberry extract not known Design: RCT over 6 months. End point UTI (clinical symptoms only)	The risk of recurrence of UTI was 60% higher in the cranberry group (not significantly different). Trimethoprim had a limited advantage, but more adverse effects	McMurdo et al^Citation61
Population: 928 residents of long-term care facilities (703 women, median age 84) stratified according to UTI risk (long-term catheterization, diabetes, UTI in preceding year) Intervention: cranberry (500 mg with 9 mg PAC) or placebo capsules twice daily Design: double-blind placebo-controlled RCT in two strata based on UTI risk over 1 year with incidence of UTI as primary outcome	No difference was found in participants with low UTI risk (n=413), but in those with a high risk (n=516) the incidence of clinical UTI was lower in the cranberry-treated group (63 vs 85 per 100 person-years at risk) This was true also for a strict definition of UTI. An economic evaluation carried out alongside with this trial did not find the prophylaxis with cranberries to be cost-effective, even not in the high-risk group	Caljouw et al^Citation42 and Van den Hout et al^Citation43
Population: 367 (mean age 81.5 years) older patients of both sexes in hospitals without previous history of UTI Intervention: daily ingestion of 300 mL cranberry juice or matching placebo beverage for a mean of 18 days Design: randomized, placebo-controlled, double-blind trial. End point: symptomatic UTI	UTI occurred in only 21/376 (5.6%) participants without differences between the groups (14/189 in the placebo group and 7/187 in the cranberry juice group). Infections with E. coli were significantly reduced in the cranberry group (13 vs 4)	McMurdo et al^Citation51
Population: 12 women (25-70 years old) with at least six UTI in the preceding year Intervention: twice daily intake of 200 mg concentrated cranberry extract standardized to 30% phenolics Design: open-label pilot study with 12-week duration of intervention. Follow-up for further 2 years. Recurrence of UTI reported by questionnaire	No UTI occurring during intake; 8/12 women remaining free of infection 2 years later	Bailey et al^Citation52
Trials in children
Population: 192 children (85 < 1 year, 107 > 1 years) with recurrent UTI Intervention: trimethoprim or cranberry, in weight-adapted dosages Design: double-blind observational trial with 75 patients receiving trimethoprim and 117 receiving cranberry over 1 year	Cranberry was not inferior to trimethoprim only in the children > 1 year old	Fernandez-Puentes et al^Citation62
Population: 40 children (39 girls) with median age of 7years Intervention: daily consumption of either cranberry juice with high content in PAC, or cranberry juice without PACs Design: RCT, blinded, for 12 months	65% risk reduction of UTI in the group receiving high PAC cranberry juice vs the juice with no PAC	Afshar et al^Citation58
Population: 263 children with a history of UTI Intervention: cranberry juice containing 41 g of cranberry concentrate/L 300 mL per day for 6 months Design: double-blind placebo-controlled RCT with an observation period of 1 year	Twenty children in the cranberry group and 28 in the placebo group had at least one recurrent UTI (ns). UTI incidence density per person- year at risk was 0.16 episodes lower in the cranberry group (95% Cl, -0.3 1 to -0.01; P=0.035). The children in the cranberry group had significantly fewer days on antimicrobials (-6 days per patient-year; 95% Cl, -7 to-5; P<0.001)	Salo et al^Citation57
Trials in children and adults with chronic genito-urinary disorders due to malformations or neu
Population: 20 children (mean age 7.25 years) with neurogenic bladder caused by myelomeningocele Intervention: placebo or cranberry extract tablets daily Design: RCT, double-blinded, with cross-over design: 6 vs 6 months	Reduction of symptomatic UTI in the cranberry group from 0.5/year (placebo) to 0/year, and also of pyuria	Mutlu et al^Citation66
Population: 171 outpatients with urinary disorders (eg, self-catherization) due to multiple sclerosis Intervention: cranberry extract (36 mg PAC/day) or matching placebo taken twice daily Design: prospective RCT in eight centers over 1 year with primary end point of time to first symptomatic UTI	No difference in time to first symptomatic UTI between cranberry and placebo There had been high drop-out rates and a low rate of UTI during the observation period	Gallien et al^Citation39
Population: 40 children with neuropathic bladder needing intermittent catheterization Intervention: 15 mL/kg/day cranberry cocktail or water Design: randomized single-blind cross-over study	High drop-out rate, only 21 finished trial. No effect greater than that of water on UTI occurrence	Foda et al^Citation65
Population: 15 children with neurogenic bladder receiving intermittent catheterization Intervention: cranberry concentrate or placebo concentrate Design: double-blind, placebo-controlled cross-over study for 6 months, change of intervention after 3 months. Urine samples were taken during weekly visits by catheterization, and infection symptoms recorded	No change of the high UTI prevalence of 75% by cranberry juice consumption. E. coli remained the predominant pathogen during placebo and cranberry periods	Schlager et al^Citation69
Population: 15 spinal cord injured patients (mean age 42 years) Intervention: commercial cranberry juice (three times 250 mL/day) Design: pilot study with open cross-over design to determine whether alteration of fluid intake and use of cranberry juice affects influenced biofilm generation. Urine samples investigated for bacterial biofilm load after 7 days drinking three glasses of water daily and after further 7 days of drinking three glasses of cranberry juice daily. Urine samples used to harvest uroepithelial cells to look for biofilm coating and to test for bacterial adhesion	Cranberry juice intake reduced the biofilm load compared with baseline (P=0.013) and the adhesion of Gram-negative (P=0.054) and Gram- positive (P=0.022) bacteria to cells. Water intake had no effect on bacterial adhesion or biofilm presence	Reid et al^Citation68
Population: 305 spinal cord-injured patients with neurogenic bladder and stable bladder management Intervention: methenamine hippurate 1 g twice daily or 800 mg cranberry extract twice daily, both indistinguishable in taste and appearance Design: double-blind randomized placebo-controlled trial with 6 months follow-up. The main outcome measure was time to occurrence of a symptomatic UTI	Both treatment groups had no longer UTI-free periods than placebo groups (P=0.70 for cranberry; P=0.75 for methenamine hippurate)	Lee et al^Citation67
Population: persons with spinal cord injury with neurogenic bladder managed by intermittent catheterization or external collection device and bacteriuria. Twenty-six persons received cranberry extract and 22 persons received placebo Intervention: daily ingestion of capsules with 2 g of concentrated cranberry juice or placebo for 6 months Design: randomized, double-blind, placebo-controlled study. Baseline urinalysis and cultures were performed at the time of the initial clinic visit and monthly for 6 months Trial in renal transplant patients	No differences or trends detected between participants and controls with respect to bacterial counts, types and numbers of different bacterial species, leukocyturia, urinary pH, or episodes of symptomatic urinary tract infection	Waites et al^Citation70
Population: 82 renal transplant recipients with recurrent UTI Intervention: prophylaxis with cranberry juice (two times 50 mL/day, n=39, or L-methionine (three times 500 mg/day, n=25, or both (n=l8) vs 30 patients without prophylaxis Design: retrospective analysis of UTI events, pyuria/nitriuria during 1 year before vs after initiation of prophylaxis	Prophylaxis decreased annual UTI by 58% with no change in control group. Cranberry reduced by 64%, L-methionine by 49%	Pagonas et al^Citation77

Abbreviations: CI, confidence interval; PAC, proanthocyanidin; RCT, randomized controlled trial; TMP-SMX, trimethoprim sulfamethoxazole; UTI, urinary tract infection; ns, not significant.

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