Purpose: Urinary tract infections (UTIs) are widespread and affect a large portion of the human population. Cranberry juices and extracts have been used for UTI prevention due to their content of bioactive proanthocyanidins (PACs), particularly of the A type (PAC-A). Controversial clinical results obtained with cranberry are often due to a lack of precise determination and authentication of the PAC-A content. This study used OximacroReg. (Biosfered S.r.l., Turin, Italy), a cranberry extract with a high content of PAC-A, to prevent UTIs in female and male volunteers. Materials and Methods: The OximacroReg. PACs content was assayed using the Brunswick Laboratories 4-dimethylaminocinnamaldehyde (BL-DMAC) method, and the dimer and trimer PACs-A and PACs-B percentages were determined via high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ESI-MS/MS). A balanced group of female (ranging from 19 to over 51 years) and male volunteers (over 51 years) was divided into two groups. The experimental group received 1 capsule containing OximacroReg. (36 mg PACs-A) twice per day (morning and evening) for 7 days, and the placebo group was given the same number of capsules with no PACs. Results: Analysis of OximacroReg. revealed a high total PAC content (372.34 mg/g+or-2.3) and a high percentage of PAC-A dimers and trimers (86.72%+or-1.65). After 7 days of OximacroReg. administration, a significant difference was found between the placebo and OximacroReg. groups for both females (Mann-Whitney U-test=875; P=.001; n=60) and males (Mann-Whitney U-test=24; P=.016; n=10). When the female and male age ranges were analysed separately, the female age range 31-35 showed only slightly significant differences between the placebo and OximacroReg. groups (Mann-Whitney U-test=20.5; P=.095; n=10), whereas all other female age ranges showed highly significant differences between the placebo and OximacroReg. groups (Mann-Whitney U-test=25; P=.008; n=10). Furthermore, colony forming unit/mL counts from the urine cultures showed a significant difference (P<.001) between the experimental and the placebo groups (SD difference=51688; df=34, t=-10.27; Dunn-Sidak Adjusted P<.001, Bonferroni Adjusted P<.001). Conclusion: Careful determination of the total PAC content using the BL-DMAC method and the authentication of PACs-A with mass spectrometry in cranberry extracts are necessary to prepare effective doses for UTI prevention. A dose of 112 mg OximacroReg. containing 36 mg PACs-A was found to be effective in preventing UTIs when used twice per day for 7 days.

Objective: We assessed the effects of the consumption of a cranberry beverage on episodes of clinical UTIs.

Design: In this randomized, double-blind, placebo-controlled, multicenter clinical trial, women with a history of a recent UTI were assigned to consume one 240-mL serving of cranberry beverage/d (n = 185) or a placebo (n = 188) beverage for 24 wk. The primary outcome was the clinical UTI incidence density, which was defined as the total number of clinical UTI events (including multiple events per subject when applicable) per unit of observation time.

Results: The dates of the random assignment of the first subject and the last subject’s final visit were February 2013 and March 2015, respectively. The mean age was 40.9 y, and characteristics were similar in both groups. Compliance with study product consumption was 98%, and 86% of subjects completed the treatment period in both groups. There were 39 investigator-diagnosed episodes of clinical UTI in the cranberry group compared with 67 episodes in the placebo group (antibiotic use–adjusted incidence rate ratio: 0.61; 95% CI: 0.41, 0.91; P = 0.016). Clinical UTI with pyuria was also significantly reduced (incidence rate ratio: 0.63; 95% CI: 0.40, 0.97; P = 0.037). One clinical UTI event was prevented for every 3.2 woman-years (95% CI: 2.0, 13.1 woman-years) of the cranberry intervention. The time to UTI with culture positivity did not differ significantly between groups (HR: 0.97; 95% CI: 0.56, 1.67; P = 0.914).

Conclusion: The consumption of a cranberry juice beverage lowered the number of clinical UTI episodes in women with a recent history of UTI. This study was registered at clinicaltrials.gov as NCT01776021.

Full article: http://ajcn.nutrition.org/content/103/6/1434.full

Most research on American cranberry in the prevention of urinary tract infection (UTI) has used juices. The spectrum of components in juice is limited. This study tested whether whole cranberry fruit powder (proanthocyanidin content 0.56%) could prevent recurrent UTI in 182 women with two or more UTI episodes in the last year. Participants were randomized to a cranberry (n=89) or a placebo group (n=93) and received daily 500mg of cranberry for 6months. The number of UTI diagnoses was counted. The intent-to-treat analyses showed that in the cranberry group, the UTIs were significantly fewer [10.8% vs. 25.8%, p=0.04, with an age-standardized 12-month UTI history (p=0.01)]. The Kaplan-Meier survival curves showed that the cranberry group experienced a longer time to first UTI than the placebo group (p=0.04). Biochemical parameters were normal, and there was no significant difference in urinary phenolics between the groups at baseline or on day180. The results show that cranberry fruit powder (peel, seeds, pulp) may reduce the risk of symptomatic UTI in women with a history of recurrent UTIs.

Research suggests that cranberry (Vaccinium macrocarpon) helps maintain urinary tract health. Bacterial adhesion to the uroepithelium is the initial step in the progression to development of a urinary tract infection. The bacterial anti-adhesion activity of cranberry proanthocyanidins (PACs) has been demonstrated in vitro. Three different cranberry extracts were developed containing a standardized level of 36 mg of PACs. This randomized, double-blind, placebo controlled, ex vivo, acute study was designed to compare the anti-adhesion activity exhibited by human urine following consumption of three different cranberry extracts on uropathogenic P-fimbriated Escherichia coli in healthy men and women. All three cranberry extracts significantly increased anti-adhesion activity in urine. from 6 to 12 hours after intake of a single dose standardized to deliver 36 mg of PACs (as measured by the BL-DMAC method), versus placebo.

OBJECTIVE: To evaluate the existing data regarding the use of cranberry products for the prevention of urinary tract infections (UTIs) in pediatric patients.
DATA SOURCES: A literature search of Medline databases from 1966 to June 2015 was conducted.
STUDY SELECTION AND DATA EXTRACTION: The databases were searched using the terms ""pediatrics,"" ""children,"" ""cranberry,"" ""cranberry juice,"" and ""urinary tract infections."" The identified trials were then searched for additional references applicable to this topic.
DATA SYNTHESIS: A total of 8 clinical trials were identified that examined the use of cranberry products, mostly juice, for the prevention of UTIs in children. Three trials examined the use in otherwise healthy children. Five trials examined the use in pediatric patients with underlying urogenital abnormalities of which 2 compared cranberry to antibiotics. In healthy pediatric patients, cranberry use was associated with a reduction in the overall number of UTIs and a decrease in the number of antibiotic days per year for UTI treatment. In patients with urogenital abnormalities, results were conflicting, with some studies showing no reduction in UTIs compared with placebo, but others demonstrating a significant reduction. However, cranberry products had similar efficacy when compared with both cefaclor and trimethoprim. All studies used a wide variety of doses and frequencies of cranberry, making specific product recommendations difficult.
CONCLUSIONS: Cranberry appears effective for the prevention of UTIs in otherwise healthy children and is at least as effective as antibiotics in children with underlying urogenital abnormalities. However, recommendations for cranberry dosing and frequency cannot be confidently made at this time. Larger, well-designed trials are recommended.

OBJECTIVE: Cranberry prophylaxis of recurrent urinary tract infection in infants has proven effective in the experimental model of the adult. There are few data on its efficacy, safety and recommended dose in the pediatric population.
METHODS: A controlled, double-blind Phase III clinical trial was conducted on children older than 1 month of age to evaluate the efficacy and safety of cranberry in recurrent urinary tract infection. The assumption was of the non-inferiority of cranberry versus trimethoprim. Statistical analysis was performed using Kaplan Meier analysis.
RESULTS: A total of 85 patients under 1 year of age and 107 over 1 year were recruited. Trimethoprim was prescribed to 75 patients and 117 received cranberry. The cumulative rate of urinary infection associated with cranberry prophylaxis in children under 1 year was 46% (95% CI; 23-70) in children and 17% (95% CI; 0-38) in girls, effectively at doses inferior to trimethoprim. In children over 1 year-old cranberry was not inferior to trimethoprim, with a cumulative rate of urine infection of 26% (95% CI; 12-41). The cranberry was well tolerated and with no new adverse effects.
CONCLUSIONS: Our study confirms that cranberry is safe and effective in the prophylaxis of recurrent urinary tract infection in infants and children. With the doses used, their efficiency is not less than that observed for trimethoprim among those over 1 year-old. (Clinical Trials Registry ISRCTN16968287).

Background: Urinary tract infection is the most common bacterial infection in the community, mainly caused by Escherichia coli (E. coli). Due to its high incidence and recurrence, problems are faced in the treatment with antibiotics. Cranberry being herbal remedy have long been the focus of interest for their beneficial effects in preventing urinary tract infections. This study was conducted to analyse in vitro activity of cranberry (Vaccinium macrocarpon) on uropathogenic E. coli in uncomplicated urinary tract infections. Methods: In this laboratory based single group experimental study, anti-bacterial activity of Vaccinium macrocarpon concentrate on urinary tract E. coli was investigated, in vitro. Ninety-six culture positive cases of different uropathogens were identified. Vaccinium macrocarpon concentrate at different concentrations was prepared in distilled water and put in wells punched in nutrient agar. E. coli isolates were inoculated on the plates and incubated at 37 oC for 24 hours. A citric acid solution of the same pH as that of Vaccinium macrocarpon was used and put in a well on the same plate to exclude the effect of pH. Results: A total of 35 isolates of E. coli were identified out of 96 culture positive specimens of urine and found sensitive to Vaccinium macrocarpon (p<0.000). Results revealed that Vaccinium macrocarpon has antibacterial effect against E. coli. Furthermore the antibacterial activity of Vaccinium macrocarpon has dose response relationship. Acidic nature of Vaccinium macrocarpon due to its pH is not contributory towards its antibacterial effect. Conclusion: Vaccinium macrocarpon concentrate may be used in urinary tract infection caused by E. coli.

For investigation of the molecular interaction of cranberry extract with adhesins of uropathogenic Escherichia coli (UPEC), urine from four volunteers consuming standardized cranberry extract (proanthocyanidin content = 1.24%) was analyzed within ex vivo experiments, indicating time-dependent significant inhibition of 40-50% of bacterial adhesion of UPEC strain NU14 to human T24 bladder cells. Under in vitro conditions a dose-dependent increase in bacterial adhesion was observed with proanthocyanidin-enriched cranberry Vaccinium macrocarpon extract (proanthocyanidin content = 21%). Confocal laser scanning microscopy and scanning electron microscopy proved that V.m. extract led to the formation of bacterial clusters on the outer plasma membrane of the host cells without subsequent internalization. This agglomerating activity was not observed when a PAC-depleted extract (V.m. extract(PAC)) was used, which showed significant inhibition of bacterial adhesion in cases where type 1 fimbriae dominated and mannose-sensitive UPEC strain NU14 was used. V.m. extract(PAC) had no inhibitory activity against P- and F1C-fimbriae dominated strain 2980. Quantitative gene expression analysis indicated that PAC-containing as well as PAC-depleted cranberry extracts increased the fimH expression in NU14 as part of a feedback mechanism after blocking FimH. For strain 2980 the PAC-containing extract led to up-regulation of P- and F1C-fimbriae, whereas the PAC-depleted extract had no influence on gene expression. V.m. and V.m. extract(PAC) did not influence biofilm and curli formation in UPEC strains NU14 and 2980. These data lead to the conclusion that also proanthocyanidin-free cranberry extracts exert antiadhesive activity by interaction with mannose-sensitive type 1 fimbriae of UPEC.

The effectiveness of cranberry in the treatment of urinary tract infection (UTI) has been associated with its polyphenol content, particularly proanthocyanidins (PACs) and the inhibition of adherence of Escherichia coli to the uroepithelium. This paper describes a controlled, double blind, clinical trial of children aged over one month with recurrent urinary tract infection. The study aims were to evaluate the safety and efficacy of cranberry syrup in children and to investigate the relationship between the excretion of phenolic acids in urine with the antiadherent activity of cranberry syrup. In the study population, cranberry syrup was found to be similar to trimethoprim, with a rate of UTI (reinfection) of 26% (95% CI 12-41). The administration of cranberry syrup was associated with high levels of hydroxycinnamic and hydroxybenzoic acids in urine; in both cases these molecules present activity in the biofilm inhibition or reduction of surface hydrophobicity of E. coli (Clinical Trials Registry ISRCTN16968287).

OBJECTIVES: To evaluate the compliance with and tolerability of daily cranberry capsule ingestion for asymptomatic bacteriuria (ASB) prevention in pregnancy.
DESIGN: A total of 49 pregnant women from two sites were randomly assigned to cranberry or matching placebo, two doses daily, at gestational ages less than 16 weeks. Patients were followed monthly for urinary tract infection until delivery. Up to seven monthly visits were scheduled for each patient. Delivery data were evaluated.
RESULTS: Of 38 evaluable patients, the mean compliance rate over the study period was 82% (range, 20%-100%). This compliance rate and the 74% of patients achieving good (>75%) compliance were similar between those who received cranberry capsules and placebo. Compliance evaluation revealed that most patients stopped capsule consumption after 34-38 weeks of participation. Multivariate logistic regression and longitudinal analysis showed a significant interaction time effect with cranberry treatment. However, cranberry consumption was not a significant predictor of gastrointestinal intolerance or study withdrawal. Although 30% of patients withdrew for various reasons, only 1 withdrew because of intolerance to the cranberry capsules. Loss to follow-up was mostly due to provider change (9 of 49 [18%]) and therapy disinterest (4 of 49 [8%]). Seven cases of ASB occurred in 5 patients: 2 of 24 (8%) in the cranberry group and 3 of 25 (12%) in the placebo group. No cases of cystitis or pyelonephritis were observed.
CONCLUSION: One third of pregnant women could not complete the study protocol for various reasons. Compliance with and tolerability of cranberry capsule ingestion appear good; these capsules provide a potentially effective means to prevent ASB in pregnancy. Further studies with large samples are necessary to confirm the findings.