OBJECTIVE:Several studies have investigated the role of cranberry extract in the prevention of recurrent urinary tract infections (UTIs), on different selected subpopulations at increased risk of UTI. In this registry, we tested the prophylactic effects of an oral supplementation containing a highly standardized cranberry extract (Anthocran®) in young subjects with a previous history of recurrent UTIs, over a 2-months follow-up.PATIENTS AND METHODS:36 otherwise healthy subjects in juvenile age (between 12 and 18 years of age) suffering by recurrent UTIs were enrolled. Participants received either a standard management (SM) (control group, n=17) or SM associated with an oral daily supplementation (supplementation group, n=19). Oral supplementation consisted in one capsule containing 120 mg of cranberry extract (Anthocran®), standardized to 36 mg proanthocyanidins, for 60 days. The effectiveness in the prevention of UTIs was determined by: the number of UTIs evaluated two months before the inclusion in the registry and during the supplementation period; the number of symptom-free subjects during the registry period. Safety considerations and measurement of adherence to treatment were also performed.RESULTS:The two groups were comparable for age, gender distribution, the days of follow-up and also for the number of UTIs before inclusion. The mean number of UTIs observed during the registry in the supplemented group (0.31±0.2) was significantly lower compared to the control group (2.3±1.3) and to the mean number of UTIs assessed before inclusion (1.74±1.1) (p-value = 0.0001 for both). Moreover, 63.1% of supplemented subjects was symptom-free during the registry period, whereas 23.5% subjects were asymptomatic in the control group (p-value <0.05).CONCLUSIONS:This registry supplement study provides compelling evidence on the efficacy of an oral supplementation, based on a highly standardized cranberry extract (Anthocran®), as prophylaxis in young healthy subjects suffering by recurrent UTIs.

Background: Catheter-associated urinary tract infections (CAUTIs) represent over 30% of hospital-acquired infections with an annual incidence of 560,000 CAUTIs per year in the United States. An estimated 13,000 deaths are attributable to CAUTIs annually. Standard prevention strategies frequently fail to eliminate CAUTI in intensive care units. The effectiveness of a hospital-based program of cranberry products (CP) and meatal antimicrobials to prevent CAUTI in a heterogeneous ICU population has not been evaluated. Methods: Data of Foley days and incidence of CAUTI in the Critical Care Unit (CCU) and the general wards (GW) in a single 245-bed suburban medical center were collected as a part of routine infection control surveillance. Standard CAUTI prevention bundles were applied throughout the hospital in 2009. In May 2012 an intervention of applying Bacitracin ointment to the urinary meatus-Foley junction and oral cranberry juice or tablets was started only in the CCU. A retrospective review of the data collected before and after the intervention in both the GW and CCU was completed. Results: Prior to the QI intervention in May 2012, average CAUTI rates were 2.8 CAUTIs per 1000 catheter days (CI 0.26-1.89) in the CCU and 1.6 CAUTIs per 1000 catheter days (CI 0.71-4.97) on the GW (p = 0.28). After the intervention, the average number of CAUTIs/1000 days in the CCU was 0, which was significantly different from the average of 1.52 CAUTIs/1000 days (CI 0.78-2.26) on the GW (p < 0.001). Conclusion: Our data indicate that the addition of cranberry-containing products and antimicrobial meatal care may further reduce incidence of CAUTI when added to standard recommendations. Further research will be necessary to determine if these interventions could be effective in a wider population.

Background and Objectives. Recently, we described an inverse association between cranberry supplementation and serum prostate specific antigen (PSA) in patients with negative biopsy for prostate cancer (PCa) and chronic nonbacterial prostatitis. This double blind placebo controlled study evaluates the effects of cranberry consumption on PSA values and other markers in men with PCa before radical prostatectomy. Methods: Prior to surgery, 64 patients with prostate cancer were randomized to a cranberry or placebo group. The cranberry group (n=32) received a mean 30 days of 1500 mg cranberry fruit powder. The control group (n=32) took a similar amount of placebo. Selected blood/urine markers as well as free and total phenolics in urine were measured at baseline and on the day of surgery in both groups. Prostate tissue markers were evaluated after surgery. Results: The serum PSA significantly decreased by 22.5% in the cranberry arm (n=31, P<0.05). A trend to down-regulation of urinary beta-microseminoprotein (MSMB) and serum gamma-glutamyltranspeptidase, as well as upregulation of IGF-1 was found after cranberry supplementation. There were no changes in prostate tissue markers or, composition and concentration of phenolics in urine. Conclusions: Daily consumption of a powdered cranberry fruit lowered serum PSA in patients with prostate cancer. The whole fruit contains constituents that may regulate the expression of androgen-responsive genes.

Bacteriuria plus pyuria is highly prevalent among older women living in nursing homes.Cranberry capsules are an understudied, nonantimicrobial prevention strategy used in this population. Objective:To test the effect of 2 oral cranberry capsules once a day on presence of bacteriuria plus pyuria among women residing in nursing homes.Design, Setting, and Participants:Double-blind, randomized, placebo-controlled efficacy trial with stratification by nursing home and involving 185 English-speaking women aged 65 years or older, with or without bacteriuria plus pyuria at baseline, residing in 21 nursing homes located within 50 miles (80 km) of New Haven, Connecticut (August 24, 2012-October 26, 2015).Interventions:Two oral cranberry capsules, each capsule containing 36 mg of the active ingredient proanthocyanidin (ie, 72 mg total, equivalent to 20 ounces of cranberry juice) vs placebo administered once a day in 92 treatment and 93 control group participants.Main Outcomes and Measures:Presence of bacteriuria (ie, at least 105 colony-forming units [CFUs] per milliliter of 1 or 2 microorganisms in urine culture) plus pyuria (ie, any number of white blood cells on urinalysis) assessed every 2 months over the 1-year study surveillance; any positive finding was considered to meet the primary outcome. Secondary outcomes were symptomatic urinary tract infection (UTI), all-cause death, all-cause hospitalization, all multidrug antibiotic-resistant organisms, antibiotics administered for suspected UTI, and total antimicrobial administration.Results:Of the 185 randomized study participants (mean age, 86.4 years [SD, 8.2], 90.3% white, 31.4% with bacteriuria plus pyuria at baseline), 147 completed the study. Overall adherence was 80.1%. Unadjusted results showed the presence of bacteriuria plus pyuria in 25.5% (95% CI, 18.6%-33.9%) of the treatment group and in 29.5% (95% CI, 22.2%-37.9%) of the control group. The adjusted generalized estimating equations model that accounted for missing data and covariates showed no significant difference in the presence of bacteriuria plus pyuria between the treatment group vs the control group (29.1% vs 29.0%; OR, 1.01; 95% CI, 0.61-1.66; P = .98). There were no significant differences in number of symptomatic UTIs (10 episodes in the treatment group vs 12 in the control group), rates of death (17 vs 16 deaths; 20.4 vs 19.1 deaths/100 person-years; rate ratio [RR], 1.07; 95% CI, 0.54-2.12), hospitalization (33 vs 50 admissions; 39.7 vs 59.6 hospitalizations/100 person-years; RR, 0.67; 95% CI, 0.32-1.40), bacteriuria associated with multidrug-resistant gram-negative bacilli (9 vs 24 episodes; 10.8 vs 28.6 episodes/100 person-years; RR, 0.38; 95% CI, 0.10-1.46), antibiotics administered for suspected UTIs (692 vs 909 antibiotic days; 8.3 vs 10.8 antibiotic days/person-year; RR, 0.77; 95% CI, 0.44-1.33), or total antimicrobial utilization (1415 vs 1883 antimicrobial days; 17.0 vs 22.4 antimicrobial days/person-year; RR, 0.76; 95% CI, 0.46-1.25).Conclusions and Relevance:Among older women residing in nursing homes, administration of cranberry capsules vs placebo resulted in no significant difference in presence of bacteriuria plus pyuria over 1 year.Trial Registration:clinicaltrials.gov Identifier: NCT01691430.

Please see this link for the Cranberry Institute's official statement regarding this research: http://www.cranberryinstitute.org/HCP/cranutiresponse.html

OBJECTIVE: Recently, cranberry extracts have been tested as a nutritional supplementation in the prevention of lower urinary tract symptoms (LUTS) as well as recurrent urinary tract infections (UTIs) in subjects at risk, with mixed results. However, evidence of efficacy should be considered only for well-characterized and standardized products in a more selected study population. Moreover, the efficacy of these interventions in elderly must be further investigated. The aim of this pilot, registry study was to evaluate the prophylactic effects of an oral supplementation containing a highly concentrated and standardized cranberry extract reproducing the natural total profile of cranberry fruits, in elderly men with benign prostatic hyperplasia (BPH), suffering from recurrent UTIs, over a 2-months follow-up.PATIENTS AND METHODS: 43 men (age > 65 years) enrolled in this study freely decided to receive either a standard management (SM) only (n = 21) or SM associated with an oral supplementation (n = 23). Supplementation consisted in a daily administration of one capsule containing cranberry extract (Anthocran®) for 60 consecutive days. The clinical effectiveness in the prevention of UTIs was determined by the number of UTIs in the two months before the inclusion in the registry and during the supplementation period, and the number of symptom-free subjects during the registry period. Safety considerations were also performed.RESULTS: In the supplemented group, the mean number of UTI episodes reported during the registry (0.8 ± 0.5) significantly decreased compared with inclusion time (3.2 ± 1.3), p-value = 0.0001. No significant changes were observed in control, SM-only group. Importantly, the cranberry oral supplementation was superior over SM at reducing the mean number of UTIs (p-value = 0.0062).CONCLUSIONS: These results suggest that cranberry supplementation could be an effective and safe approach, within an SM program, for the prevention of recurrent UTIs in elderly men suffering from BPH avoiding some antibiotic treatments.

ABSTRACT: Cranberry is reported to have health benefits, including prevention of urinary tract infections and other chronic diseases, due to the high content of polyphenols, including flavonols and flavan-3-ols. The aim of this study was to determine the clearance of flavonol glycosides and flavan-3-ols and/or their metabolites in human urine. Ten healthy women volunteers ingested 240 mL of cranberry juice containing flavonol glycosides. Urine samples were collected at 0, 90, 225, and 360 min postingestion. While flavan-3-ols were not detected, five flavonol glycosides common in cranberry were identified. Quercetin-3-galactoside, the most abundant cranberry flavonol, exhibited the highest peak urine concentration (Cmax) of 1315 pg/mg creatinine, followed by quercetin-3-rhamnoside, quercetin-3-arabinoside, myricetin-3-arabinoside, and myricetin-3-galactoside. Quercetin-3-arabinoside showed delayed clearance, Cmax at 237 min (Tmax), relative to other flavonols (90−151 min). Both aglycone and the conjugated sugar moiety structure mediate the flavonol’s bioavailability. Interindividual variation for bioavailability and clearance is also apparent. Metabolites, e.g. glucoronides, were not detected. KEYWORDS: flavonols, glycosides, flavan-3-ols, cranberry juice, human urine, MS-MS

Cranberry has been used traditionally to prevent urinary tract infections (UTIs), primarily among generally healthy women prone to recurrent UTIs. Results from a number of published clinical studies have supported this benefit; however, meta-analyses on cranberry and UTI prevention have reported conflicting conclusions. This article explores the methodological differences that contributed to these disparate findings. Despite similar research questions, the meta-analyses varied in the studies that were included, as well as the data that were extracted. In the 2 most comprehensive systematic reviews, heterogeneity was handled differently, leading to an I2 of 65% in one and 43% in the other. Most notably, the populations influencing the conclusions varied. In one analysis, populations with pathological/physiological conditions contributed 75.6% of the total weight to the summary risk estimate (RR: 0.86; 95% CI: 0.71, 1.04); another weighted the evidence relatively equally across UTI populations (RR: 0.62; 95% CI: 0.49, 0.80); and a third included only women with recurrent UTIs (RR: 0.53; 95% CI: 0.33, 0.83). Because women with recurrent UTIs are the group to whom most recommendations regarding cranberry consumption is directed, inclusion of other groups in the efficacy assessment could influence clinical practice quality. Therefore, conclusions on cranberry and UTIs should consider differences in results across various populations studied when interpreting results from meta-analyses.

PURPOSE: To evaluate the effect of cranberry extract (PAC-A ~ proanthocyanidin-A) on the in vitro bacterial properties of uropathogenic (E. coli) and its efficacy/tolerability in patients with subclinical or uncomplicated recurrent UTI (r-UTI). MATERIALS AND METHODS: After obtaining clearance from the ethics committee and administering a written informed consent, 72 patients with r-UTI were enrolled as per protocol (November 2011 to March 2013) in this prospective study, to randomly receive (PAC-A: group I, 36) or (placebo: group II, 36), for 12 weeks. Any change/reduction in the incidence of r-UTI at 12 weeks was construed to be the primary endpoint of this study. RESULTS: After 12 weeks, bacterial adhesion scoring decreased (0.28)/(2.14) in group I/II (p < 0.001); 32/36 (88.8 %) and 2/36 (5.5 %) in groups I and II, respectively, turned MRHA negative (p < 0.001); biofilm (p < 0.01) and bacterial growth (p < 0.001) decreased in group I; microscopic pyuria score was 0.36/2.0 in group I/II (p < 0.001); r-UTI decreased to 33.33 versus 88.89 % in group I/II (p < 0.001); mean subjective dysuria score was 0.19 versus 1.47 in group I/II (p < 0.001), while mean urine pH was 5.88 versus 6.30 in group I/II (p < 0.001). No in vitro antibacterial activity of cranberry could be demonstrated, and no adverse events were noted. CONCLUSIONS: The overall efficacy and tolerability of standardized cranberry extract containing (PAC-A) as a food supplement were superior to placebo in terms of reduced bacterial adhesion; bacterial MRHA negativity; urine pH reduction; and in preventing r-UTI (dysuria, bacteriuria and pyuria). Larger randomized controlled trials are needed to elucidate the precise role, exact dose and optimal duration of PAC-A therapy in patients at risk of r-UTI.

Urinary tract infections (UTIs) are common in women and many patients with recurrent UTIs do not eradicate the condition albeit being treated with multiple courses of antibiotics. The use of nutritional supplements might reduce the risk of recurrent UTIs. However, the role of supplements taken as single agents appears to be limited. We hypothesized that a combination of cranberries, Lactobacillus rhamnosus, and vitamin C might produce a clinical benefit due to their additive or synergistic effects. We prospectively enrolled 42 consecutive women with recurrent UTIs treated with 120mg cranberries (minimum proanthocyanidin content: 32mg), 1 billion heat-killed L. rhamnosus SGL06, and 750mg vitamin C thrice daily for 20 consecutive d. Patients were advised to stop taking these supplements for 10 d and then to repeat the whole cycle three times. Patients were contacted three mo and six mo following the end of the administration of these supplements and evaluated with a semistructured interview and urinalysis. Responders were defined as the absence of symptoms and negative urinalysis or urine culture. Follow-up data were available for 36 patients. Overall, 26 (72.2%) and 22 patients (61.1%) were responders at the 3-mo and 6-month follow-up. No major side effects were recorded. The administration of cranberries, L. rhamnosus, and vitamin C might represent a safe and effective option in women with recurrent UTIs.

OBJECTIVE: To determine effects of cranberry extract on development of urinary tract infection (UTI) in dogs and on adherence of Escherichia coli to Madin-Darby canine kidney (MDCK) cells. ANIMALS: 12 client-owned dogs (in vivo experiment) and 6 client-owned dogs (in vitro experiment). PROCEDURES: 12 dogs with a history of recurrent UTI received an antimicrobial (n=6) or cranberry extract (6) orally for 6 months. Dogs were monitored for a UTI. For the in vitro experiment, cranberry extract was orally administered to 6 dogs for 60 days. Voided urine samples were collected from each dog before and 30 and 60 days after onset of extract administration. Urine was evaluated by use of a bacteriostasis assay. An antiadhesion assay and microscopic examination were used to determine inhibition of bacterial adherence to MDCK cells. RESULTS: None of the 12 dogs developed a UTI. The bacteriostasis assay revealed no zone of inhibition for any urine samples. Bacterial adhesion was significantly reduced after culture with urine samples obtained at 30 and 60 days, compared with results for urine samples obtained before extract administration. Microscopic examination revealed that bacterial adherence to MDCK cells was significantly reduced after culture with urine samples obtained at 30 and 60 days, compared with results after culture with urine samples obtained before extract administration. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of cranberry extract prevented development of a UTI and prevented E. coli adherence to MDCK cells, which may indicate it has benefit for preventing UTIs in dogs.