American Cranberry (Vaccinium macrocarpon) and Urinary tract infection (UTI): evidence and sources

Background and objective With over 50% of women suffering from at least one episode of urinary tract infection (UTI) throughout their lifetime and an increasing prevalence of antimicrobial resistance, efforts need to be made to clearly identify the evidence supporting potential non-drug interventions. This study aims to compare the effects of cranberry juice, cranberry tablets, and increased liquids for the management of UTIs. Methods PubMed, Embase, and Cochrane CENTRAL were searched for randomised controlled trials. The primary outcome was the number of UTIs, and the secondary outcomes were UTI symptoms and antimicrobial consumption. A risk of bias assessment was performed using the Cochrane risk of bias tool, and the certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. Key findings and limitations A total of 20 trials (3091 participants) were included, with 18 studies highlighting a 54% lower rate of UTIs with cranberry juice consumption than no treatment and a 27% lower rate than placebo liquid. Cranberry juice also resulted in a 49% lower rate of antibiotic use than placebo liquid and a 59% lower rate than no treatment, based on a network meta-analysis of six studies. The use of cranberry compounds also reduced the prevalence of symptoms associated with UTIs. Conclusions and clinical implications With moderate to low certainty, the evidence supports the use of cranberry juice for the prevention of UTIs. While increased liquids reduce the rate of UTIs compared with no treatment, cranberry in liquid form provides even better clinical outcomes in terms of reduction in UTIs and antibiotic use and should be considered for the management of UTIs. Patient summary With the increasing prevalence of antimicrobial-resistant UTIs, alternate non-drug treatment options for its management are required. Available evidence supports the use of cranberry compounds and increases in fluid intake for managing UTIs.

Background Cranberries contain proanthocyanidins (PACs), which inhibit the adherence of p-fimbriated Escherichia coli to the urothelial cells lining the bladder. Cranberry products have been used widely for several decades to prevent urinary tract infections (UTIs). This is the fifth update of a review first published in 1998 and updated in 2003, 2004, 2008, and 2012. Objectives To assess the effectiveness of cranberry products in preventing UTIs in susceptible populations. Search methods We searched the Cochrane Kidney and Transplant Specialised Register up to 13 March 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register Search Portal (ICTRP) and ClinicalTrials.gov. Selection criteria All randomised controlled trials (RCTs) or quasi-RCTs of cranberry products compared with placebo, no specific treatment or other intervention (antibiotics, probiotics) for the prevention of UTIs were included. Data collection and analysis Two authors independently assessed and extracted data. Information was collected on methods, participants, interventions and outcomes (incidence of symptomatic UTIs, positive culture results, side effects, adherence to therapy). Risk ratios (RR) with 95% confidence intervals (CI) were calculated where appropriate. Study quality was assessed using the Cochrane risk of bias assessment tool. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Main results For this update 26 new studies were added, bringing the total number of included studies to 50 (8857 randomised participants). The risk of bias for sequence generation and allocation concealment was low for 29 and 28 studies, respectively. Thirty-six studies were at low risk of performance bias, and 23 studies were at low risk of detection bias. Twenty-seven, 41, and 17 studies were at low risk of attrition bias, reporting bias and other bias, respectively. Forty-five studies compared cranberry products with placebo or no specific treatment in six different groups of participants. Twenty-six of these 45 studies could be meta-analysed for the outcome of symptomatic, culture-verified UTIs. In moderate certainty evidence, cranberry products reduced the risk of UTIs (6211 participants: RR 0.70, 95% CI 0.58 to 0.84; I² = 69%). When studies were divided into groups according to the treatment indication, cranberry products probably reduced the risk of symptomatic, culture-verified UTIs in women with recurrent UTIs (8 studies, 1555 participants: RR 0.74, 95% CI 0.55 to 0.99; I² = 54%), in children (5 studies, 504 participants: RR 0.46, 95% CI 0.32 to 0.68; I² = 21%) and in people with a susceptibility to UTIs due to an intervention (6 studies, 1434 participants: RR 0.47, 95% CI 0.37 to 0.61; I² = 0%). However, in low certainty evidence, there may be little or no benefit in elderly institutionalised men and women (3 studies, 1489 participants: RR 0.93, 95% CI 0.67 to 1.30; I² = 9%), pregnant women (3 studies, 765 participants: RR 1.06, 95% CI 0.75 to 1.50; I² = 3%), or adults with neuromuscular bladder dysfunction with incomplete bladder emptying (3 studies, 464 participants: RR 0.97, 95% CI 0.78 to 1.19; I² = 0%). Other comparisons were cranberry products with probiotics (three studies) or antibiotics (six studies), cranberry tablets with cranberry liquid (one study), and different doses of PACs (two studies). Compared to antibiotics, cranberry products may make little or no difference to the risk of symptomatic, culture-verified UTIs (2 studies, 385 participants: RR 1.03, 95% CI 0.80 to 1.33; I² = 0%) or the risk of clinical symptoms without culture (2 studies, 336 participants: RR 1.30, 95% CI 0.79 to 2.14; I² = 68%). Compared to probiotics, cranberry products may reduce the risk of symptomatic, culture-verified UTIs (3 studies, 215 participants: RR 0.39, 95% CI 0.27 to 0.56; I = 0%). It is unclear whether efficacy differs between cranberry juice and tablets or between different doses of PACs as the certainty of the evidence was very low. The number of participants with gastrointestinal side effects probably does not differ between those taking cranberry products and those receiving placebo or no specific treatment (10 studies, 2166 participants: RR 1.33, 95% CI 1.00 to 1.77; I² = 0%; moderate certainty evidence). There was no clear relationship between compliance with therapy and the risk for repeat UTIs. No difference in the risk for UTIs could be demonstrated between low, moderate and high doses of PACs. Authors' conclusions This update adds a further 26 studies taking the total number of studies to 50 with 8857 participants. These data support the use of cranberry products to reduce the risk of symptomatic, culture-verified UTIs in women with recurrent UTIs, in children, and in people susceptible to UTIs following interventions. The evidence currently available does not support its use in the elderly, patients with bladder emptying problems, or pregnant women.

The efficacy of cranberry (Vaccinium spp.) as adjuvant therapy in preventing urinary tract infections (UTIs) remains controversial. This study aims to update and determine cranberry effects as adjuvant therapy on the recurrence rate of UTIs in susceptible groups. According to PRISMA guidelines, we conducted a literature search in Web of Science, PubMed, Embase, Scopus, and the Cochrane Library from their inception dates to June 2021. We included articles with data on the incidence of UTIs in susceptible populations using cranberry-containing products. We then conducted a trial sequential analysis to control the risk of type I and type II errors. This meta-analysis included 23 trials with 3979 participants. We found that cranberry-based products intake can significantly reduce the incidence of UTIs in susceptible populations (risk ratio (RR) = 0.70; 95% confidence interval(CI): 0.59 ~ 0.83; P<0.01). We identified a relative risk reduction of 32%, 45% and 51% in women with recurrent UTIs (RR = 0.68; 95% CI: 0.56 ~ 0.81), children (RR = 0.55; 95% CI: 0.31 ~ 0.97) and patients using indwelling catheters (RR = 0.49; 95% CI: 0.33 ~ 0.73). Meanwhile, a relative risk reduction of 35% in people who use cranberry juice compared with those who use cranberry capsule or tablet was observed in the subgroup analysis (RR = 0.65; 95% CI: 0.54 ~ 0.77). The TSA result for the effects of cranberry intake and the decreased risk of UTIs in susceptible groups indicated that the effects were conclusive. In conclusion, our meta-analysis demonstrates that cranberry supplementation significantly reduced the risk of developing UTIs in susceptible populations. Cranberry can be considered as adjuvant therapy for preventing UTIs in susceptible populations. However, given the limitations of the included studies in this meta-analysis, the conclusion should be interpreted with caution.

Introduction Urinary tract infections (UTIs) represent a common and costly public health issue. The bacterium Escherichia coli is mainly responsible for most uncomplicated UTIs. Cranberry antibacterial effects have extensively been studied in order to understand the molecular mechanisms of action of its bioactive components and their clinical benefits against UTIs. In this respect, the present review aims to critically analyze the current clinical studies that have evaluated the efficacy of supplementing cranberry products against UTIs in different subpopulations. Methods PubMed database was comprehensively searched, using relative keywords in order to identify clinical trials exploring the efficacy of cranberry supplementation against UTIs. Results Current clinical evidence clearly indicates a possible benefit overall from the use of cranberries against UTIs. Cranberry consumption may prevent bacterial adherence to uroepithelial cells, reducing UTI related symptoms. Cranberry consumption could also decrease UTI related symptoms by suppressing inflammatory cascades as an immunologic response to bacterial invasion. The existing clinical trials have supported substantial evidence that the beneficial effects of cranberry against UTIs seem to be prophylactic by preventing infections recurrence; however, they exert low effectiveness in populations at increased risk for contracting UTIs. Moreover, a lack of cost-effectiveness for cranberry supplementation has been highlighted. Conclusions Additional well-designed, double-blind, placebo-controlled clinical trials that use standardized cranberry products for long study periods are strongly recommended in order to determine the efficiency of cranberry on the prevention of UTIs in susceptible populations. At present, cranberry supplementation can safely be suggested as complementary therapy in women with recurrent UTIs.

Background: Cranberry ( Vaccinium spp.) has been advocated for treatment of urinary tract infection (UTI); however, its efficacy is controversial. Women have a 50% risk of UTI over their lifetime, and ∼20-30% experience a subsequent UTI recurrence. Objective: We conducted this meta-analysis to assess the effect of cranberry on the risk of UTI recurrence in otherwise healthy women. Methods: Literature published before January 2011 was obtained from 2 published systematic reviews, and we conducted updated searches in EMBASE and MEDLINE (through July 2017). We included randomized controlled trials that were conducted in generally healthy nonpregnant women aged ≥18 y with a history of UTI, compared cranberry intervention to a placebo or control, and reported the outcome as the number of participants experiencing a UTI. Two researchers conducted abstract and full-text screenings, data extractions, and risk of bias assessments independently, and discrepancies were resolved by group consensus. Meta-analyses were performed by using Stata SE software (version 13). We employed a fixed-effect model using the Mantel-Haenszel method to estimate the summary risk if the heterogeneity was low to moderate ( I 2 Results: We identified 7 randomized controlled trials conducted in healthy women at risk of UTI ( n = 1498 participants). Results of the meta-analysis showed that cranberry reduced the risk of UTI by 26% (pooled risk ratio: 0.74; 95% CI: 0.55, 0.98; I 2 = 54%). Risk of bias indicated that 2 studies had high loss to follow-up or selective outcome reporting. Overall, the studies were relatively small, with only 2 having >300 participants. Conclusion: These results suggest that cranberry may be effective in preventing UTI recurrence in generally healthy women; however, larger high-quality studies are needed to confirm these findings. This trial was registered at crd.york.ac.uk/prospero as CRD42015024439.

Cranberries exert a dose-dependent inhibition of the adherence of E. coli fimbriae to uroepithelial cells. This was demonstrated in vitro but also ex vivo in vitro with urine from cranberry consumers. The active principle has not been identified in detail but type-A proanthocyanidins (PAC) play an important role in the mechanism of action. Since the three species, American cranberry (Vaccinium macrocarpon), European cranberry (Vaccinium oxycoccus) and/or lingonberry (Vaccinium vitis-idaea), have different patterns of type-A PACs, results from one species cannot be transferred to the others. It seems likely that most of the studies with monopreparations from V. macrocarpon were underdosed. Whereas photometric PAC quantification may overestimate the true content on co-active compounds, reversed phase high-performance liquid chromatograpy may underestimate them. Recent studies with PAC doses in the upper range (DMAC method) or declared type-A PAC content in the daily dose reveal a dose-dependent trend of clinical effectiveness, however, with a possible ceiling effect. In order to clarify this, future three-arm studies should investigate Vaccinium preparations with higher type-A PAC doses than previously used. We analysed two popular European vitis-idaea products, a mother juice and a proprietary extract. Both preparations may be appropriate to confirm the Vaccinium urinary tract infection-preventive effect beyond doubt.

Aim To review the scientific publications concerning the clinical use and mechanism of action of the North American cranberry (Vaccinium macrocarpon) for women with recurrent urinary tract infections (UTI) and other health conditions. Methods This is a retrospective study of published information concerning Vaccinium macrocarpon retrieved from a PubMed and individual searches. Results Urinary tract infections are very common in women, cause discomfort, and may aggravate other genitourinary conditions. The available scientific information supports a clinical benefit of Vaccinium macrocarpon in the prevention of recurrent UTI in women. There is a non-significant reduction of UTI associated with Vaccinium macrocarpon treatment during pregnancy. A group of proanthocyanidins (PAC) with A-type linkages have been isolated from Vaccinium macrocarpon which inhibit P-fimbriae synthesis and induce a bacterial deformation, on both antibiotic-susceptible and antibiotic-resistant uropathogenic Escherichia coli. It is plausible that cranberry PAC prevent bacteria from adhering to the uroepithelium of the bladder, thereby blocking the ability of E. coli to infect the urinary mucosa. Conclusion Cranberry treatment is a safe, well-tolerated supplement that does not have significant drug interactions. Although investigations are in the early stages, experimental and preclinical studies suggest that cranberry components may have other potential benefits, including anti-infective, anticancer and antioxidant effects, which may be considered as positive for different age-related conditions. In addition, cranberry components may induce positive cardiovascular and metabolic changes, and may improve neuropsychological activity. These effects warrant further clinical research to better place the role of cranberry products for women.

Background Τhe adherence of p-fimbriated Escherichia coli (E. coli) to urothelial cells leading to recurrent urinary tract infections (rUTIs) may be prevented by proanthocyanidins (PACs) contained in American cranberries. Purpose The purpose of this clinical trial was to assess the clinical utility of prophylactic use of high-dose PACs daily in women with a history of rUTIs. Materials and methods 172 adult women with a history of rUTIs, defined as ≥ 2 within a 6-month period or ≥ 3 within a 12-month period were enrolled and randomized in two groups to receive either Cysticlean™ 240 mg or placebo for a 12-month period. Urine samples, vaginal and rectal swabs were collected at initial and quarterly study visits. The primary study endpoints were the number of urinary tract infections (UTIs) and changes in Quality of Life (QoL), assessed by the 36-Item Short Form Survey (SF-36) questionnaire. Results 160 adult women of median age 40 years old (range 19-82) were finally analyzed in this randomized, placebo-controlled, double-blinded clinical trial. In response to intervention, the number of UTIs was significantly lower (Incidence rate ratio IRR 0.49, p Conclusion The daily use of Cysticlean™ 240 mg was associated with a reduction of UTIs and a prolongation of UTI-free survival compared to placebo treatment, supporting its use as prophylaxis in this patient population. Trial registration Clinicaltrials.gov, identifier NCT03032003.

Purpose Our objective was to assess the efficacy of a high dose cranberry proanthocyanidin extract for the prevention of recurrent urinary tract infection. Material and methods We recruited 145 healthy, adult women with a history of recurrent urinary tract infection, defined as ≥ 2 in the past 6 months or ≥ 3 in the past 12 months in this randomized, controlled, double-blind clinical trial. Participants were randomized to receive a high dose of standardized, commercially available cranberry proanthocyanidins (2 × 18.5 mg daily, n = 72) or a control low dose (2 × 1 mg daily, n = 73) for a 24-week period. During follow-up, symptomatic women provided urine samples for detection of pyuria and/or bacteriuria and received an appropriate antibiotic prescription. The primary outcome for the trial was the mean number of new symptomatic urinary tract infections during a 24-week intervention period. Secondary outcomes included symptomatic urinary tract infection with pyuria or bacteriuria. Results In response to the intervention, a non-significant 24% decrease in the number of symptomatic urinary tract infections was observed between groups (Incidence rate ratio 0.76, 95%CI 0.51-1.11). Post-hoc analyses indicated that among 97 women who experienced less than 5 infections in the year preceding enrolment, the high dose was associated with a significant decrease in the number of symptomatic urinary tract infections reported compared to the low dose (age-adjusted incidence rate ratio 0.57, 95%CI 0.33-0.99). No major side effects were reported. Conclusion High dose twice daily proanthocyanidin extract was not associated with a reduction in the number of symptomatic urinary tract infections when compared to a low dose proanthocyanidin extract. Our post-hoc results reveal that this high dose of proanthocyanidins may have a preventive impact on symptomatic urinary tract infection recurrence in women who experienced less than 5 infections per year. Trial registration Clinicaltrials.gov, identifier NCT02572895.

Background Urinary tract infections (UTIs) are among the most common bacterial infections and are often treated with antibiotics. Concerns about multidrug-resistant uropathogens have pointed to the need for safe and effective UTI-prevention strategies such as cranberry consumption. 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.

Cranberry ( Vaccinium macrocarpon ) is a distinctive source of polyphenols as flavonoids and phenolic acids that has been described to display beneficial effects against urinary tract infections (UTIs), the second most common type of infections worldwide. UTIs can lead to significant morbidity, especially in healthy females due to high rates of recurrence and antibiotic resistance. Strategies and therapeutic alternatives to antibiotics for prophylaxis and treatment against UTIs are continuously being sought after. Different to cranberry, which have been widely recommended in traditional medicine for UTIs prophylaxis, probiotics have emerged as a new alternative to the use of antibiotics against these infections and are the subject of new research in this area. Besides uropathogenic Escherichia coli (UPEC), the most common bacteria causing uncomplicated UTIs, other etiological agents, such as Klebsiella pneumoniae or Gram-positive bacteria of Enterococcus and Staphylococcus genera, seem to be more widespread than previously appreciated. Considerable current effort is also devoted to the still-unraveled mechanisms that are behind the UTI-protective effects of cranberry, probiotics and their new combined formulations. All these current topics in the understanding of the protective effects of cranberry against UTIs are reviewed in this paper. Further progresses expected in the coming years in these fields are also discussed.