Abstract: Urinary tract infections (UTIs) are one the of the most common types of infections in adults older than 65 years of age. Preventing UTIs with prophylactic antibiotics increases the risk of side effects and microbial resistance, and is costly. Cranberry fruit and juices contain the compound proanthrocyanidins (PACs), specifically proanthrocyanidin-A, which exerts antiadhesion characteristics against bacteria. Cranberry products therefore have been an attractive, nonantibiotic preventative option for UTIs; however, the current literature supporting cranberry use in older adults is controversial. This could be multifactorial owing to the heterogeneity of the older population as well as inconsistencies in the recommended dose of PAC in the current literature. Evidence supports that cranberry may be beneficial in preventing UTIs in specific populations such as catheterassociated UTI and postradiotherapy prostate cancer. The cost of daily capsules versus the cost of preventing a UTI in older adults is an important consideration for initiating therapy.
Abstract: BACKGROUND: Urinary tract infections (UTIs) are common in pregnancy and account for the highest proportion of primary care antibiotic prescriptions issued to pregnant women in the UK. It is well known that antibiotic use is associated with increased antimicrobial resistance and therefore measures to minimise antibiotic use for UTI prevention have been studied. The efficacy and safety of these measures in pregnancy have not been addressed and therefore the aim of this study was to systematically review the literature to identify and evaluate potential measures to prevent UTIs in pregnant women. METHODS: Ten databases (EMBASE, AMED, BNI, CINAHL, Medline, PubMed, PsycINFO, Cochrane Trials, Scopus and Science Direct) were systematically searched in July 2017 for studies reporting non-antibiotic measures to prevent UTIs in pregnancy. The terms ("urinary tract infection" or UTI or bacteriuria or cystitis) AND (prevention) AND (pregnan*) were used. The quality of the publications was appraised using the Critical Appraisal Skills Programme (CASP) checklists for cohort study, case-control study and randomised controlled trial. The results were synthesised using a textual narrative approach. RESULTS: Search results yielded 3276 publications and after reviewing titles and removing duplicates, 57 full text articles were assessed for eligibility and eight were included in the review. Five different approaches (hygiene measures, cranberry juice, immunisation, ascorbic acid and Canephron N) have been identified, all of which are reported to be safe in pregnancy. CONCLUSION: The quality of the evidence varied considerably and only hygiene measures were supported by evidence to be recommended in practice. Future work needs to concentrate on strengthening the evidence base through improved design and reporting of studies with a focus on immunisation, ascorbic acid and Canephron N.
Abstract: This article describes the chemical composition, efficacy and risks of using cranberries for the treatment of cystitis in cats and dogs.
Abstract: The American cranberry (Vaccinium macrocarpon) is one of the fruits containing antioxidants in great quantity and of high quality. From recent research, it is evident that both cranberry and its products, when consumed chronically or acutely, boost the antioxidant effect. Likewise, most studies revealed the anti-inflammatory potential of the cranberry polyphenols. Both effects exert direct action mechanisms, revealed by the ability of the polyphenols to remove the reactive oxygen species, as well as indirect effects, represented by the action of these phytochemicals on the cell signaling pathways and genetic expression. A limited number of articles that evaluated the effects of cranberry on mitochondrial damages are available. However, an enhancement in the functions of this organelle was confirmed by the increased production of adenosine triphosphate (ATP). Therefore, further studies are required to demonstrate the benefits credited to the use of cranberry, as well as to describe the action mechanisms of the polyphenols.
Abstract: Chitosan interacts with proanthocyanidins through hydrogen-bonding, which allows encapsulation and development of stable nanoparticles via ionotropic gelation. Cranberry proanthocyanidins (PAC) are associated with the prevention of urinary tract infections and PAC inhibit invasion of gut epithelial cells by extra-intestinal pathogenic Escherichia coli (ExPEC). We determined the effect of cranberry proanthocyanidin-chitosan hybrid nanoparticles (PAC-CHTNp) on the ExPEC invasion of gut epithelial cells in vitro. PAC-CHTNp were characterized according to size, morphology, and bioactivity. Results showed a decrease in the size of the nanoparticles as the concentration of PAC was increased, indicating that PAC increases cross-linking by hydrogen-bonding on the surface of the chitosan nanoparticles. Nanoparticles were produced with diameters ranging from 367.3nm to 293.2nm. Additionally, PAC-CHTNp significantly inhibited the ability of ExPEC to invade the enterocytes by ~80% at 66mugGAE/mL and by ~92% at 100mugGAE/mL. Results also indicate that chitosan nanoparticles alone were not significantly different from controls in preventing ExPEC invasion of enterocytes (data not shown) and also there were not significant differences between PAC alone and PAC-CHTNp, suggesting that the new PAC-CHTNp could lead to an increase in the stability of encapsulated PAC, maintain the molecular adhesion of PAC to ExPEC.
Abstract: OBJECTIVES: Urinary tract infections (UTIs) are common after pelvic reconstructive surgery, likely due to high rates of urinary retention. We sought to determine if prescription of cranberry capsules reduced UTIs in postoperative patients requiring catheter use. METHODS: This was an institutional review board-approved retrospective cohort study. Two 6-month periods were compared: April to September 2015, before cranberry capsules were incorporated, and April to September 2016, after cranberry capsules were implemented. Our study population included patients discharged with a catheter after pelvic reconstructive surgery. All charts were reviewed for demographics, perioperative data, and urine cultures up to 6 weeks postoperatively. A UTI was defined as treatment with antibiotics or positive cultures. Statistical analysis was performed; logistic regression evaluated for relationships between UTI and other factors. Our a priori sample size calculation determined 88 subjects per group would be necessary. RESULTS: Over the 2 periods, 167 patients met inclusion criteria: 71 before and 96 after cranberry implementation. The 2 cohorts were similar in all data. Regarding incidence of UTI, rates were overall high and not significantly different between groups (76% before cranberry vs 69% with cranberry; P = 0.299). The median duration of catheter use was 8 days in both cohorts. The UTI was most likely to occur in the second week after surgery. Logistic regression revealed no associations between age, surgery type, duration of catheter use, and UTI. CONCLUSIONS: In this retrospective study, prescription of cranberry capsules did not significantly reduce UTI rates among patients with urinary catheters after pelvic reconstructive surgery.
Abstract: Candida albicans is one of the most common causes of hospital-acquired urinary tract infections (UTIs). However, azoles are poorly active against biofilms, echinocandins do not achieve clinically useful urinary concentrations, and amphotericin B exhibits severe toxicities. Thus, novel strategies are needed to prevent Candida UTIs, which are often associated with urinary catheter biofilms. We previously demonstrated that cranberry-derived proanthocyanidins (PACs) prevent C. albicans biofilm formation in an in vitro urinary model. To elucidate functional pathways unique to urinary biofilm development and PAC inhibition, we investigated the transcriptome of C. albicans in artificial urine (AU), with and without PACs. C. albicans biofilm and planktonic cells were cultivated with or without PACs. Genome-wide expression analysis was performed by RNA sequencing. Differentially expressed genes were determined using DESeq2 software; pathway analysis was performed using Cytoscape. Approximately 2,341 of 6,444 total genes were significantly expressed in biofilm relative to planktonic cells. Functional pathway analysis revealed that genes involved in filamentation, adhesion, drug response and transport were up-regulated in urinary biofilms. Genes involved in carbon and nitrogen metabolism and nutrient response were down-regulated. In PAC-treated urinary biofilms compared to untreated control biofilms, 557 of 6,444 genes had significant changes in gene expression. Genes downregulated in PAC-treated biofilms were implicated in iron starvation and adhesion pathways. Although urinary biofilms share key features with biofilms formed in other environments, many genes are uniquely expressed in urinary biofilms. Cranberry-derived PACs interfere with the expression of iron acquisition and adhesion genes within urinary biofilms.
Abstract: BACKGROUND: The effects of un-extruded (UCP) and extruded cranberry pomace (ECP) on fecal fat excretion, liver index, lipid and carbohydrate metabolism, and inhibition of oxidative stress due to a high-fat diet (HFD) in rats were studied. METHODS: The Wistar rats for 8 weeks received one of the four diets: (1) control (modified the American Institute of Nutrition: AIN based diet containing 7% fat), (2) HFD (AIN based diet containing 30% fat), (3) HFD with 3% un-extruded (UCP) and (4) HFD with 3% (ECP). RESULTS: Both UCP and ECP significantly improved the plasma antioxidant capacity and decreased lipid per- oxidation in rats fed a HFD. However, only the addition of 3% UCP into the HFD significantly increased the fecal lipid excretion and considerably decreased serum triglycerides level in rats. CONCLUSIONS: Further investigation is needed to determine the role of an individual components present in UCP and ECP in the improvement of metabolic conditions observed in the current study.
Abstract: Uropathogenic Escherichia coli (UPEC) is the main infectious agent of urinary tract infections (UTI) in humans, dogs and cats. Dietary consumption of cranberries is thought to be associated with prevention of UTI in humans based on decreased adhesion of UPEC to uroepithelial cells. The present study evaluated the impact of cranberry extract addition on the attachment of UPEC to canine Madin-Darby Canine Kidney and Crandell-Rees Feline Kidney uroepithelial cells. When the extract was present during bacterial growth or only during adhesion tests, a dose-dependent decrease of UPEC adhesion to all cell types was observed. Bacterial growth was weakly decreased only in the presence of the highest concentration of cranberry extract showing that the anti-adherence effect did not require a bacterial growth inhibitory effect. In conclusion, the addition of cranberry extract has preventive effects on the in vitro bacterial attachment to canine and feline uroepithelial cells in a dose dependent way.
Abstract: Uropathogenic Escherichia coli (UPEC), the most prevalent bacteria isolated in urinary tract infections (UTI), is now frequently resistant to antibiotics used to treat this pathology. The antibacterial properties of cranberry and propolis could reduce the frequency of UTIs and thus the use of antibiotics, helping in the fight against the emergence of antibiotic resistance. Transcriptomic profiles of a clinical UPEC strain exposed to cranberry proanthocyanidins alone (190micro g/mL), propolis alone (102.4micro g/mL) and a combination of both were determined. Cranberry alone, but more so cranberry+propolis combined, modified the expression of genes involved in different essential pathways: down-expression of genes involved in adhesion, motility, and biofilm formation, and up-regulation of genes involved in iron metabolism and stress response. Phenotypic assays confirmed the decrease of motility (swarming and swimming) and biofilm formation (early formation and formed biofilm). This study showed for the first time that propolis potentiated the effect of cranberry proanthocyanidins on adhesion, motility, biofilm formation, iron metabolism and stress response of UPEC. Cranberry+propolis treatment could represent an interesting new strategy to prevent recurrent UTI.
Abstract: Study design: This study was a double-blind, placebo-controlled trial of a concentrated PACs compound (36mg/capsule), in veterans with SCI and neurogenic lower urinary tract dysfunction (NLUTD) requiring intermittent catheterization (IC) over a 15-day period. Objectives: The objective of this study was to evaluate the acute effects of concentrated proanthocyanidins (PACs) in the cranberry supplement ellura on bacteriuria, leukocyturia, and subjective urine quality in catheter-dependent veterans with SCI. Setting: Spinal cord injury center (outpatient clinic and inpatient unit). Methods: Participants with positive urine bacterial colonization (>=50K CFU/ml) were randomized to once daily concentrated PACs or identical placebo and followed with daily (in-patients) or twice weekly (out-patients) urine cultures with colony forming units per milliliter (cfu/ml) range (bacteriuria), microscopic urine white blood cells per high-powered field (wbc/hpf) quantification (leukocyturia), and surveys assessing urine clarity, odor, color, sediment, and overall satisfaction. A repeated measure analysis of variance was used to compare treatment vs. control and evaluate serial trends. Results: A total of 13 male participants (7 randomized to concentrated PACs, 6 to placebo) completed the trial. There was no significant decrease over the study period in colony forming units per milliliter (cfu/ml) or log(wbc/hpf) in the treatment vs. the control group. Patients receiving concentrated PACs rated the clarity, odor, color, sediment, and overall satisfaction of their urine as insignificantly improved compared to placebo. Conclusions: Acutely, there was no reduction of bacteriuria and pyuria or improvement in subjective urine quality for SCI patients treated with daily concentrated PACs.
Abstract: Background/Aims: Clinical trials of older adults are increasingly common, but risks of serious adverse events (SAE) may vary. We describe the incidence of SAE in two randomized trials, one community-based and one nursing home-based. Methods: We performed a secondary data analysis from two randomized clinical trials at one academic health center and 21 nursing homes involving 200 sedentary community dwellers aged 70-89 years and 185 female nursing home residents aged 65 years or older. Interventions included structured physical activity to reduce mobility disability in the Lifestyle Interventions and Independence for Elders (LIFE) study and oral cranberry capsules to reduce bacteriuria plus pyuria in nursing home residents (CRANNY) trial. We measured SAE incidence per 100 person-years and incidence of protocol-related unanticipated SAE per 100 person-years in LIFE and CRANNY trials. Results: Mean age and proportion of patients with dementia in LIFE and CRANNY trials were 79.3 years and 86.4 years and 0% and 78%, respectively. There were 179 total SAE in LIFE including 8 (4%) deaths, and 116 total SAE in CRANNY including 33 (28%) deaths. SAE incidence was 33.7 (95% CI 27.2, 41.8) events per 100 person-years in LIFE and 69.4 (95% CI 49.1, 98.1) events per 100 person-years in CRANNY. No protocol-related unanticipated SAE occurred in either trial. Conclusions: The frequency and severity of SAE vary in older adults. While SAE are common in nursing home residents, protocol-related, unanticipated SAE are rare in nursing home residents and community dwellers. This finding can inform trial monitoring protocols.
Abstract: BACKGROUND: Urinary tract infections (UTIs) are amongst the most common bacterial infections affecting women. Although antibiotics are the treatment of choice for UTI, cranberry derived products have been used for many years to prevent UTIs, with limited evidence as to their efficacy. Our objective is to assess the efficacy of a cranberry extract capsule standardized in A-type linkage proanthocyanidins (PACs) for the prevention of recurrent urinary tract infection. METHODS: We will perform a 1:1 randomized, controlled, double blind clinical trial in women aged 18 years or more who present >=2 UTIs in 6 months or>=3 UTIs in 12 months. One hundred and forty-eight women will be recruited and randomized in two groups to either receive an optimal dose of cranberry extract quantified and standardized in PACs (2x18.5 mg PACs per day) or a control dose (2x1 mg PACs per day). The primary outcome for the trial is the mean number of new symptomatic UTIs in women during a 6-month intervention period. Secondary outcomes are: (1) To evaluate the mean number of new symptomatic UTIs with pyuria as demonstrated by a positive leucocyte esterase test; (2) To detect the mean number of new symptomatic culture-confirmed UTIs; (3) To quantify urinary PACs metabolites in women who take a daily dose of 37 mg PACs per day compared to women who take a daily dose of 2 mg per day for 6 months; (4) To characterize women who present recurrent UTI based on known risk factors for recurrent UTI; (5) To describe the side effects of daily intake of cranberry extract containing 37 mg PACs compared to 2 mg PACs. This report provides comprehensive methodological data for this randomized controlled trial. DISCUSSION: The results of this trial will inform urologists, gynaecologists, family physicians and other healthcare professionals caring for healthy women with recurrent UTI, as to the benefits of daily use of an optimal dose of cranberry extract for the prevention of recurrent UTI.
Abstract: The defense against influenza virus (IV) infections still poses a series of challenges. The current antiviral arsenal against influenza viruses is in fact limited; therefore, the development of new anti-influenza strategies effective against antigenically different viruses is an urgent priority. Bioactive compounds derived from medicinal plants and fruits may provide a natural source of candidates for such broad-spectrum antivirals. In this regard, cranberry (Vaccinium macrocarpon Aiton) extracts on the basis of their recognized anti-adhesive activities against bacteria, may provide potential compounds able to prevent viral attachment to target cells. Nevertheless, only few studies have so far investigated the possible use of cranberry extracts as an antiviral tool. This study focuses on the suitability of a cranberry extract as a direct-acting anti-influenza compound. We show that the novel cranberry extract Oximacro inhibits influenza A and B viruses (IAV, IBV) replication in vitro because of its high content of A-type proanthocyanidins (PAC-A) dimers and trimers. Mechanistic studies revealed that Oximacro prevents attachment and entry of IAV and IBV into target cells and exerts a virucidal activity. Oximacro was observed to interact with the ectodomain of viral hemagglutinin (HA) glycoprotein, thus suggesting the interference with HA functions and a consequent loss of infectivity of IV particles. Fluorescence spectroscopy revealed a reduction in the intrinsic fluorescence of HA protein after incubation with purified dimeric PAC-A (PAC-A2), thus confirming a direct interaction between HA and Oximacro PAC-A2. In silico docking simulations further supported the in vitro results and indicated that among the different components of the Oximacro chemical profile, PAC-A2 exhibited the best binding propensity with an affinity below 10 nM. The role of PAC-A2 in the anti-IV activity of Oximacro was eventually confirmed by the observation that it prevented IAV and IVB replication and caused the loss of infectivity of IV particles, thus indicating PAC-A2 as the major active component of Oximacro. As a whole, these results suggest Oximacro as a potential candidate to create novel antiviral agents of natural origin for the prevention of IV infections.
Abstract: Objective: The objective of this study was to assess relationships between clinical predictors of urinary tract infection (UTI) and effects of cranberry juice consumption on recurrence in a post hoc analysis of a 24-week, randomized, double-blind, placebo-controlled, multicenter clinical trial in women with a recent history of UTI. Methods: Participants consumed a cranberry (n=185) or placebo (n=188) beverage (240 mL) daily. Odds ratios (OR) from 20 candidate predictor variables were evaluated in univariate analyses to assess clinical UTI incidence relationships in the placebo group. A multivariate logistic regression model was developed. The effects of cranberry juice consumption were evaluated in subsets categorized by the likelihood of a UTI event based on the prediction model. Results: In the placebo group, the final multivariate regression model identified four variables associated with the odds for having >=1 UTI: intercourse frequency >=1 time during the prior 4 weeks (OR: 2.36; 95% confidence interval [CI]: 0.98, 5.71; p=0.057), use of vasectomy or hormonal methods for contraception (OR: 2.58; 95% CI: 1.20, 5.58; p=0.016), most recent UTI <90 days prior to screening (OR: 2.28; 95% CI; 1.12, 4.67; p=0.024), and living in France compared with the United States (OR: 0.17; 95% CI: 0.04, 0.79; p=0.024). Three propensity categories were investigated (24-week probability <10%, 10%-21%, and >21%). Incidence rate ratios for the cranberry vs placebo groups were 0.76 (95% CI: 0.22, 2.60; p=0.663) for those with <10% probability, 0.73 (95% CI: 0.35, 1.53; p=0.064) for those with 10% to 21% probability, and 0.58 (95% CI: 0.35, 0.97; p=0.039) for those with >21% probability. Conclusions: Results suggest that clinical predictors identify women with low and high risk of clinical UTI recurrence, which may be useful for design of clinical studies evaluating preventive therapies.
Abstract: The relationship among diet, human health, and disease is an area of growing interest in biomarker research. Previous studies suggest that the consumption of cranberries (Vaccinium macrocarpon) could beneficially influence urinary and digestive health. The present study sought to determine if daily consumption of sweetened dried cranberries (SDC) changes the urinary proteome and fecal microbiome, as determined in a prospective sample of 10 healthy individuals. Baseline urine and fecal samples were collected from the subjects in the fasted (8-12h) state. The subjects then consumed one serving (42g) of SDC daily with lunch for 2 weeks. Urine and fecal samples were collected again the day after 2 weeks of SDC consumption. Orbitrap Q-Exactive mass spectrometry of urinary proteins showed that consumption of SDC resulted in changes to 22 urinary proteins. Multiplex sequencing of 16S ribosomal RNA genes in fecal samples indicated changes in relative abundance of several bacterial taxonomic units after consumption of SDC. There was a shift in the Firmicutes:Bacteroidetes ratio, increases in commensal bacteria, and decreases or the absence of bacteria associated with negative health effects. A decrease in uromodulin in all subjects and an increase in Akkermansia bacteria in most subjects were observed and warrant further investigation. Future larger clinical studies with multiomics and multitissue sampling designs are required to determine the effects of SDC consumption on nutrition and health.
Abstract: PURPOSE: The study was conducted to investigate the effects of training provided by researcher and the use of cranberry capsule in preventing late term UTIs after urostomy. METHODS: The study included 60 patients who underwent ileal conduit diversion between June 2013 and November 2014. The participants were randomly divided into three groups. First group used cranberry capsule, second group received training about UTIs and the other control group. The patients were assessed for a UTI by laboratory analysis at 2, 3, and 4 months after discharge. RESULTS: When the effect of cranberry capsule use and training on the prevention of urinary tract infections were compared, we found that there was a significant difference between the group that used and didn't use cranberry capsules, favoring the cranberry capsule (log-rank test; p < 0.05). CONCLUSION: We found that the use of cranberry capsules is effective in the prevention of urinary tract infections.
Abstract: OBJECTIVE: The Affordable Care Act (ACA) established the Hospital-Acquired Condition (HAC) Reduction Program. The Centers for Medicare and Medicaid Services (CMS) established a total HAC scoring methodology to rank hospitals based upon their HAC performance. Hospitals that rank in the lowest quartile based on their HAC score are subject to a 1% reduction in their total Medicare reimbursements. In FY 2017, 769 hospitals incurred payment reductions totaling $430 million. This study analyzes how improvements in the rate of catheter-associated urinary tract infections (CAUTI), based on the implementation of a cranberry-treatment regimen, impact hospitals' HAC scores and likelihood of avoiding the Medicare-reimbursement penalty. METHODS: A simulation model is developed and implemented using public data from the CMS' Hospital Compare website to determine how hospitals' unilateral and simultaneous adoption of cranberry to improve CAUTI outcomes can affect HAC scores and the likelihood of a hospital incurring the Medicare payment reduction, given results on cranberry effectiveness in preventing CAUTI based on scientific trials. The simulation framework can be adapted to consider other initiatives to improve hospitals' HAC scores. RESULTS: Nearly all simulated hospitals improved their overall HAC score by adopting cranberry as a CAUTI preventative, assuming mean effectiveness from scientific trials. Many hospitals with HAC scores in the lowest quartile of the HAC-score distribution and subject to Medicare reimbursement reductions can improve their scores sufficiently through adopting a cranberry-treatment regimen to avoid payment reduction. LIMITATIONS: The study was unable to replicate exactly the data used by CMS to establish HAC scores for FY 2018. The study assumes that hospitals subject to the Medicare payment reduction were not using cranberry as a prophylactic treatment for their catheterized patients, but is unable to confirm that this is true in all cases. The study also assumes that hospitalized catheter patients would be able to consume cranberry in either juice or capsule form, but this may not be true in 100% of cases. CONCLUSION: Most hospitals can improve their HAC scores and many can avoid Medicare reimbursement reductions if they are able to attain a percentage reduction in CAUTI comparable to that documented for cranberry-treatment regimes in the existing literature.
Abstract: PURPOSE: Cranberry supplements are commonly used as a natural deterrent to urinary tract infection. However, one small study (n=5) which showed an increase in urinary oxalate levels following cranberry supplementation has led to its use with caution among patients susceptible to nephrolithiasis. Furthermore, most commonly available cranberry tablet preparations contain vitamin C, which has been independently shown to increase urinary oxalate excretion. The aim of this study is to investigate the influence of cranberry supplementation on urinary oxalate excretion. METHODS: Fifteen participants were randomised to receive cranberry tablets alone or cranberry tablets containing vitamin C. Tablets were taken at the manufacturers recommended dosage for a period of 14 days. Participants provided a 24 h urine collection at trial entry and day 14. Urinary variables were compared to assess for changes in oxalate levels. RESULTS: The median age was 27 years (21-43). There was no difference in the 24 h urine volume pre or post commencement of cranberry tablets (1.7 vs 2 L, p=0.07). An increase in median urinary oxalate excretion was observed in participants taking both cranberry-only tablets (0.10 mmol/day) and tablets containing vitamin C (1.15 mmol/day). CONCLUSION: Dietary supplementation with cranberry increases urinary oxalate excretion and should be avoided in patients at risk of urolithiasis.
Abstract: Urinary tract infections are common infectious diseases which can occur in any part of the urinary tract such as bladder, kidney, ureters, and urethra. They are commonly caused by bacteria that enter through the urethra. Urinary tract infections commonly develop in the bladder and spread to renal tissues. Up to now, there are different antimicrobial agents which have beneficial role on urinary tract infections. However, most of them cause different adverse effects and therefore, much attention has been paid to the search for effective therapeutic agents with negligible adverse effects. Cranberry is known as one of the most important edible plants, which possesses potent antimicrobial effects against the bacteria responsible for urinary tract infections. Growing evidence has shown that cranberry suppresses urinary tract infections and eradicates the bacteria. Therefore, the aim of this study is to critically review the available literature regarding the antimicrobial activities of cranberry against urinary tract infection microorganisms. In addition, we discuss etiology, epidemiology, risk factors, and current drugs of urinary tract infections to provide a more complete picture of this disease.
Abstract: 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 (I2 < 50%). Otherwise, we applied a random-effects model using the DerSimonian-Laird method.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; I2 = 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.
Abstract: INTRODUCTION: Catheter-associated urinary tract infections (CA-UTIs) are a prevalent and costly condition, with very few therapeutic options. We sought to evaluate the efficacy of an oral cranberry supplement on CA-UTIs over a six-month period. METHODS: Subjects with long-term indwelling catheters and recurrent symptomatic CA-UTIs were enrolled to take a once-daily oral cranberry supplement with 36 mg of the active ingredient proanthocyanidin (PACs). Primary outcome was reducing the number of symptomatic CA-UTIs. This was defined by >=103 (cfu)/mL of >=1 bacterial species in a single catheter urine specimen and signs and symptoms compatible with CA-UTI. Secondary outcomes included bacterial counts and resistance patterns to antibiotics. RESULTS: Thirty-four patients were enrolled in the trial; 22 patients (mean age 77.22 years, 77.27% were men) completed the study. Cranberry was effective in reducing the number of symptomatic CA-UTIs in all patients (n=22). Resistance to antibiotics was reduced by 28%. Furthermore, colony counts were reduced by 58.65%. No subjects had adverse events while taking cranberry. CONCLUSIONS: The cranberry supplement reduced the number of symptomatic CA-UTIs, antibiotic resistances, and major causative organisms in this cohort. Larger, placebo-controlled studies are needed to further define the role of cranberry in CA-UTIs.
Abstract: BACKGROUND: Individuals with spinal cord injury (SCI) consume more dietary supplements than the general population. However, there is limited information regarding the clinical effectiveness of dietary supplements in SCI population. OBJECTIVE: To systematically review the effectiveness of dietary supplements for the prevention or treatment of health-related conditions associated with SCI. METHODS: Randomized or non-randomized controlled clinical trials were selected, comparing the effect of any dose and form of a dietary supplement (defined by the Dietary Supplement Health and Education Act), with either no treatment, placebo, or other medication. Data Sources included the Cochrane Database, DARE, LILACS, CINAHL, EMBASE, MEDLINE, OTSeeker, PEDro, PsycINFO, SpeechBITE, ScienceDirect, Scopus, clinicaltrials.gov, Google Scholar, and OpenGrey. Two reviewers independently classified articles from January 1970 through October 2015, and 18 articles were selected. RESULTS: Due to the heterogeneity of outcome measures across studies, a meta-analysis was not conducted. However, high-quality evidence showed that cranberry supplementation is not effective for prevention of urinary tract infections (UTIs) in SCI. Moderate-quality evidence supported a beneficial effect of vitamin D, alpha-lipoic acid, and omega-3 supplementation, although replication of results is needed. There were conflicting results for the effect of creatine supplementation on improvement of motor outcomes. Low-quality evidence does not permit assessment of the effectiveness of melatonin, whey protein, vitamin C, and Chinese herb in SCI. CONCLUSIONS: There is sufficient data suggesting that cranberry supplementation is ineffective for prevention of UTIs in individuals with SCI. There is insufficient data to support or refute the use of any other dietary supplement in individuals with SCI.
Abstract: OBJECTIVE: The objective of this study was to assess relationships between clinical predictors of urinary tract infection (UTI) and effects of cranberry juice consumption on recurrence in a post hoc analysis of a 24-week, randomized, double-blind, placebo-controlled, multicenter clinical trial in women with a recent history of UTI. METHODS: Participants consumed a cranberry (n = 185) or placebo (n = 188) beverage (240 mL) daily. Odds ratios (OR) from 20 candidate predictor variables were evaluated in univariate analyses to assess clinical UTI incidence relationships in the placebo group. A multivariate logistic regression model was developed. The effects of cranberry juice consumption were evaluated in subsets categorized by the likelihood of a UTI event based on the prediction model. RESULTS: In the placebo group, the final multivariate regression model identified four variables associated with the odds for having >= 1 UTI: intercourse frequency >= 1 time during the prior 4 weeks (OR: 2.36; 95% confidence interval [CI]: 0.98, 5.71; p = 0.057), use of vasectomy or hormonal methods for contraception (OR: 2.58; 95% CI: 1.20, 5.58; p = 0.016), most recent UTI < 90 days prior to screening (OR: 2.28; 95% CI; 1.12, 4.67; p = 0.024), and living in France compared with the United States (OR: 0.17; 95% CI: 0.04, 0.79; p = 0.024). Three propensity categories were investigated (24-week probability < 10%, 10%-21%, and > 21%). Incidence rate ratios for the cranberry vs placebo groups were 0.76 (95% CI: 0.22, 2.60; p = 0.663) for those with < 10% probability, 0.73 (95% CI: 0.35, 1.53; p = 0.064) for those with 10% to 21% probability, and 0.58 (95% CI: 0.35, 0.97; p = 0.039) for those with > 21% probability. CONCLUSIONS: Results suggest that clinical predictors identify women with low and high risk of clinical UTI recurrence, which may be useful for design of clinical studies evaluating preventive therapies.
Abstract: Introduction: Although effectiveness of cranberry for preventing urinary tract infection (UTI) has been reported in Iranian traditional medicine and recent studies there is still controversy in this regard. Therefore, the present study was designed with a meta-analytic approach aiming to evaluate the effect of prophylaxis prescription of cranberry in prevention of UTI in children.Methods: In this study, a thorough search was performed in Medline, Embase, Web of Sciences, Scopus and CINHAL databases by the end of August 2017. Using keywords related to urinary tract infection combined with words related to cranberry, search strategy was designed. The articles were summarized and finally, the role of cranberry extract consumption in decreasing the incidence of UTI was evaluated by reporting odds ratio (OR) and 95 confidence interval (95 CI). Results: In the end, 10 studies were included (414 cases in control group and 380 in cranberry extract treatment group). Analyses showed that prescription of cranberry significantly reduced the odds of UTI manifestation in children compared to placebo (OR=0.31; 95 CI: 0.21 to 0.46; p
Abstract: Cranberry (Vaccinium macrocarpon Aiton) is used to treat noncomplicated urinary tract infections (UTIs). A-type procyanidins (PAC-A) are considered the active constituents able to inhibit bacterial adhesion to the urinary epithelium. However, the role of PAC-A in UTIs is debated, because of their poor bioavailability, extensive metabolism, limited knowledge about urinary excretion, and contradictory clinical trials. The effects of 35-day cranberry supplementation (11 mg/kg PAC-A, 4 mg/kg PAC-B) were studied in healthy rats using a ultra performance liquid chromatography-mass spectrometry (UPLC-MS)-based metabolomics approach. Microbial PAC metabolites, such as valeric acid and valerolactone derivatives, were related to cranberry consumption. An increased urinary excretion of glucuronidated metabolites was also observed. In a further experiment, urine samples were collected at 2, 4, 8, and 24 h after cranberry intake and their antiadhesive properties were tested against uropathogenic Escherichia coli. The 8 h samples showed the highest activity. Changes in urinary composition were studied by ultra performance liquid chromatography-time-of-flight (UPLC-QTOF), observing the presence of PAC metabolites. The PAC-A2 levels were measured in all collected samples, and the highest amounts, on the order of ng/mL, were found in the samples collected after 4 h. Results indicate that the antiadhesive activity against uropathogenic bacteria observed after cranberry consumption is ascribable to PAC-A metabolites rather than to a direct PAC-A effect, as the measured PAC-A levels in urine was lower than those reported as active in the literature.
Abstract: PURPOSE: We sought to clarify the association between cranberry intake and the prevention of urinary tract infections. MATERIALS AND METHODS: This systematic review, which complies with the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) statement, was done as a meta-analysis and trial sequential analysis of clinical trials. RESULTS: The findings clearly showed the potential use of cranberries for the clinical condition of urinary tract infection. Cranberry products significantly reduced the incidence of urinary tract infections as indicated by the weighted risk ratio (0.6750, 95% CI 0.5516-0.7965, p <0.0001). The results of subgroup analysis demonstrated that patients at some risk for urinary tract infections were more susceptible to the effects of cranberry ingestion. CONCLUSIONS: The results of the current study could be used by physicians to recommend cranberry ingestion to decrease the incidence of urinary tract infections, particularly in individuals with recurrent urinary tract infections. This would also reduce the administration of antibiotics, which could be beneficial since antibiotics can lead to the worldwide emergence of antibiotic resistant microorganisms.
Abstract: OBJECTIVE: To evaluate whether cranberries are able to prevent postoperative urinary bacteriuria in patients undergoing pelvic surgery and receiving transurethral catheterisation.DESIGN: Randomised, double-blind, placebo-controlled trial.SETTINGS: French tertiary Care centre, University Hospital.POPULATION: A total of 272 women undergoing pelvic surgery aged 18 or older.METHODS: Participants undergoing pelvic surgery were randomised to 36 mg cranberry (proanthocyanidins, PAC) or placebo once daily for 10 days. Statistical analysis was performed by a chi-square test.MAIN OUTCOME MEASURES: The primary and secondary outcomes were postoperative bacteriuria, defined by a positive urine culture, within the first 15 and 40 days, respectively.RESULTS: Two hundred and fifty-five participants received the intended treatment: 132 (51.8%) received PAC and 123 (48.2%) received placebo. There were no significant differences in baseline demographics, intra-operative characteristics or duration and type of catheterisation between the two groups. PAC prophylaxis did not reduce the risk of bacteriuria treatment within 15 days of surgery [27% bacteriuria with PAC compared with 25% bacteriuria with placebo: relative risk 1.05, 95% CI 0.78-1.4, P = 0.763). The same result was observed on day 40. Bacteriuria occurred more often in older women with increased length of catheterisation.CONCLUSION: Immediate postoperative prophylaxis with PAC does not reduce the risk of postoperative bacteriuria in patients receiving short-term transurethral catheterisation after pelvic surgery.
Abstract: F4+ E. coli and F18+ E. coli infections are an important threat for pig industry worldwide. Antibiotics are commonly used to treat infected piglets, but the emerging development of resistance against antibiotics raises major concerns. Hence, alternative therapies to prevent pigs from F4+ E. coli and F18+ E. coli infections need to be developed. Since cranberry previously showed anti-adhesive activity against uropathogenic E. coli, we aimed to investigate whether cranberry extract could also inhibit binding of F4+ E. coli and F18+ E. coli to pig intestinal epithelium. Using the in vitro villus adhesion assay, we found that low concentrations of cranberry extract (20 micro g or 100 micro g/ml) have strong inhibitory activity on F4+ E. coli (75.3%, S.D.=9.31 or 95.8%, S.D.=2.56, respectively) and F18+ E. coli adherence (100% inhibition). This effect was not due to antimicrobial activity. Moreover, cranberry extract (10 mg or 100 mg) could also abolish in vivo binding of F4 and F18 fimbriae to the pig intestinal epithelium in ligated loop experiments. Finally, two challenge experiments with F18+ E. coli were performed to address the efficacy of in-feed or water supplemented cranberry extract. No effect could be observed in piglets that received cranberry extract only in feed (1 g/kg or 10 g/kg). However, supplementation of feed (10 g/kg) and drinking water (1 g/L) significantly decreased excretion and diarrhea. The decreased infection resulted in a decreased serum antibody response indicating reduced exposure to F18+ E. coli.
Abstract: The antibacterial effect of cranberry juice and the organic acids therein on infection by uropathogenic Escherichia coli was studied in an experimental mouse model of urinary tract infection (UTI). Reduced bacterial counts were found in the bladder (P < 0.01) of mice drinking fresh cranberry juice. Commercially available cranberry juice cocktail also significantly reduced (P < 0.01) bacterial populations in the bladder, as did the hydrophilic fraction of cranberry juice (P < 0.05). Quinic, malic, shikimic, and citric acid, the preponderant organic acids in cranberry juice, were tested in combination and individually. The four organic acids also decreased bacterial levels in the bladder when administered together (P < 0.001), and so did the combination of malic plus citric acid (P < 0.01) and malic plus quinic acid (P < 0.05). The other tested combinations of the organic acids, and the acids administered singly, did not have any effect in the UTI model. Apparently, the antibacterial effect of the organic acids from cranberry juice on UTI can be obtained by administering a combination of malic acid and either citric or quinic acid. This study show for the first time that cranberry juice reduce E. coli colonization of the bladder in an experimental mouse model of urinary tract infection and that the organic acids are active agents.
Abstract: BACKGROUND: Urinary tract infection (UTI) is a common complication among patients with hip fractures. Receiving an indwelling urinary catheter is a risk factor for developing UTIs. Treatment of symptomatic UTIs with antibiotics is expensive and can result in the development of antimicrobial resistance. Cranberries are thought to prevent UTI. There is no previous research on this potential effect in patients with hip fracture who receive urinary catheters. AIM: The aim of this study is to investigate whether intake of cranberry juice concentrate pre-operatively decreases the incidence of postoperative UTIs in hip fracture patients that received a urinary catheter. DESIGN: This study employed a randomized, placebo-controlled double-blind trial. METHOD: Female patients, aged 60 years and older, with hip fracture (n=227) were randomized to receive cranberry or placebo capsules daily, from admission, until 5 days postoperatively. Urine cultures were obtained at admission, 5 and 14 days postoperatively. In addition, Euro Qual five Dimensions assessments were performed and patients were screened for UTI symptoms. RESULT: In the intention-to-treat analysis, there was no difference between the groups in the proportion of patients with hospital-acquired postoperative positive urine cultures at any time point. When limiting the analysis to patients that ingested at least 80% of the prescribed capsules, 13 of 33 (39%) in the placebo group and 13 of 47 (28%) in the cranberry group (P=0.270) had a positive urine culture at 5 days postoperatively. However, this difference was not statistically significant (P=0.270). CONCLUSION: Cranberry concentrate does not seem to effectively prevent UTIs in female patients with hip fracture and indwelling urinary catheter.
Abstract: BACKGROUND: Dogs with spinal cord injury are at increased risk of developing bacteriuria due to increased residual urine volume. Cranberry extract inhibits binding of E. coli to uroepithelial cells, potentially reducing risk of bacteriuria. HYPOTHESIS: Cranberry extract reduces risk of bacteriuria in dogs after acute TL-IVDH. ANIMALS: Client-owned dogs with acute onset TL-IVDH causing nonambulatory status. METHODS: Randomized, placebo-controlled, blinded, prospective clinical trial. Dogs with acute TL-IVDH were recruited 48 hours postoperatively and randomized to receive cranberry extract or placebo in a masked fashion. Urine cultures and neurological examinations were performed 2, 4, and 6 weeks postoperatively. The number of dogs with bacteriuria (all bacterial species) and bacteriuria (E. coli) were primary and secondary outcome measures and were evaluated using chi-squared test. Urine antiadhesion activity (AAA) was measured in a subset (N = 47) and examined in a secondary analysis evaluating additional risk factors for bacteriuria. RESULTS: Bacteriuria was detected 17 times in 94 dogs (6 placebo, 11 cranberry, P = .12). There were 7 E. coli. positive cultures (1 placebo, 6 cranberry, P = .09). Dogs in both groups had positive urine AAA (14/21: placebo, 16/26: cranberry), and dogs with urine AAA had significantly fewer E. coli positive cultures (n = 1) than dogs without it (n = 4) (P = .047). CONCLUSIONS AND CLINICAL IMPORTANCE: This clinical trial did not show a benefit of oral cranberry extract but had low power. Cranberry extract supplementation did not impact urine AAA, but a possible association between urine AAA and lower risk of E. coli bacteriuria was identified. Other doses could be investigated.
Abstract: INTRODUCTION: Worldwide, bacterial resistance to antibiotic therapy is a major concern for the medical community. Antibiotic resistance mainly affects Gram-negative bacteria that are an important cause of lower urinary tract infections (LUTIs). Pelvic irradiation for prostate cancer is a risk factor for LUTIs. Cranberry extract is reported to reduce the incidence of LUTIs. The prophylactic role of an enteric-coated, highly standardized cranberry extract (VO370) in reducing LUTI episodes, urinary discomfort, and nonsteroidal anti-inflammatory drug (NSAID) and antibiotic use during radiotherapy for prostate carcinoma was evaluated.METHODS: A total of 924 patients with prostate carcinoma treated by radiotherapy to the prostatic and pelvic areas were randomized to receive (n=489) or not (n=435) the enteric-coated, highly standardized cranberry extract for 6-7 weeks concurrently with irradiation. Outcomes were analyzed by using Mann-Whitney U test and Pearson's chi2 test. Primary endpoint was the number of patients with LUTI; secondary endpoints were incidence of recurrence, days of treatment with antibiotics and number of subjects treated with NSAIDs, and incidence of dysuria.RESULTS: The treatment was very well tolerated, and there were no serious side effects. All enrolled patients completed the study. Urinary infections were detected in 53 of the 489 patients (10.8%) treated with enteric-coated, highly standardized cranberry extract, while 107 of the 435 patients (24.6%) in the control group developed LUTIs (p=0.0001). A clear and significant reduction in urinary discomfort of ~50% was seen in treated subjects. The treatment also resulted in ~50% reduction in the use of anti-inflammatory drugs and antibiotics. CONCLUSION: The enteric-coated, highly standardized cranberry extract could be used as a prophylactic to reduce the incidence of LUTIs and decrease antibiotic therapy in patients receiving pelvic irradiation for prostate cancer.
Abstract: BACKGROUND:The female genital apparatus, the urinary tract and the perineal supporting tissues share a common embryological origin, whose differentiation depends on the action of estrogens. In adult women, the progressive decline of the ovarian function, with the ensuing estrogen deprivation, reduces tissue tropism causing urogenital atrophy, which makes these organs much more susceptible to traumatisms and urinary infections. The disorders associated with changes in the urogenital tract of peri- and postmenopausal women have significant clinical relevance, both on account of their chronicity and high frequency of occurrence and on account of their having major repercussions on the quality of life of the women, who often have to call their doctor seeking relief for their symptoms. In general, these patients report having a significant number of episodes of cystitis per year. With a view to verifying whether the use of a new dietary supplement (Kistinox® Forte sachets) containing cranberry (Vaccinium macrocarpon), Noxamicina® (propolis extract) and D-mannose can be of use in the treatment of cystitis, with or without bacteriuria, through the elimination of urinary symptoms, a multicenter clinical study was conducted on 150 women aged 40 to 50 suffering from recurrent episodes of cystitis as attested by at least one positive urine culture during the six months preceding their recruitment.METHODS:The subjects were randomly assigned to two groups: Group A: 100 women were given Kistinox® Forte, 1 sachet per day during the first 10 days of the month, for 3 months; Group B: 50 women did not receive any treatment to serve as a control group.RESULTS:The results of the present study show a complete remission of urinary symptoms in 92 women; a slight decrease in urinary symptoms was observed in 5 subjects, whereas 3 women who stopped the treatment after the first cycle were considered drop-outs.CONCLUSIONS:This multicenter clinical study revealed the excellent efficacy and tolerability of Kistinox® Forte sachets in the treatment and prevention of urinary disorders in peri- and postmenopausal women. The posology of a sachet a day during the first 10 days of the month for 3 months was well tolerated by the patients, who did not report any disorder arising from the product.
Abstract: 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.
Abstract: 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.
Abstract: 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
Abstract: 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: 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
Abstract: 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.
Abstract: 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.
Abstract: 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.
Abstract: 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.
Abstract: 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
Abstract: 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.
Abstract: 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.
Abstract: 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.
Abstract: 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).
Abstract: 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.
Abstract: 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.
Abstract: 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).
Abstract: 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.
Abstract: The overall metabolic changes caused by cranberry juice or apple juice consumption using a global 1H NMR-based metabolomics approach were investigated. Eighteen female college students were given either cranberry or apple juice for three days using a cross-over design. Plasma and urine samples were collected and analyzed using 1H NMR-based metabolomics followed by multivariate analyses. No metabolic difference was observed in plasma before and after juice consumption. However, metabolome in plasma and urine after cranberry juice consumption were different from those after apple juice consumption. Cranberry juice consumption caused a greater increase in urinary excretion of hippuric acid and a higher level of citric acid in the plasma. Furthermore, cranberry juice decreased the plasma level of lactate, D-glucose, and two unidentified metabolites compared to apple juice consumption. The metabolomic changes caused by cranberry juice consumption may help to explain its reported health benefits.
Abstract: In this study, we examined the ex vivo urinary anti-adhesion activity of low-calorie cranberry extract beverages in both a pilot study (n = 10) and a randomized, double-blind, placebo controlled clinical trial (n = 59). In the pilot study, subjects consumed a cranberry extract beverage (CEB) or a cranberry extract and juice beverage (CEJB), compared to placebo. Both cranberry beverages utilized a standardized cranberry extract powder at a level equivalent to low-calorie cranberry juice cocktail (LCJC) on a PAC content basis. Clean-catch urine samples collected at baseline and post intervention were tested for anti-adhesion activity utilizing a mannose-resistant human red blood cell hemagglutination assay specific for P-fimbriated E. coli. Results from the pilot study indicated that ex vivo anti-adhesion activity for both cranberry treatments were higher (p < 0.05) than placebo. In the clinical trial, we compared CEJB to LCJC and a placebo beverage. Post-consumption urine from both cranberry treatment groups showed significantly higher (p < 0.05) anti-adhesion activity compared to placebo. There were no differences observed in anti-adhesion activity between CJEB and LCJC, indicating similar bioactivity. Therefore, acute beverage consumption of cranberry extract and/or juice provides ex vivo anti-adhesion activity, which may help to improve urinary tract health.
Abstract: INTRODUCTION: Urinary tract infection (UTI) is among the most frequent complications after urinary tract surgical procedures, mainly when catheter placement is necessary. Although the use of American cranberry has been related with a reduced risk of UTI, there is no study reporting the value of its prevention effect against catheter-associated urinary tract infections.
MATERIAL AND METHODS: A prospective trial comparing UTI rate (positive urine culture) among 31 patients with double J catheter (JJ) and adding American cranberry (120 mg) in routine prophylactic therapy, and 31 patients with JJ catheter only receiving routine prophylactic therapy.
RESULTS: Regarding general characteristics of the populations no significant difference among groups have been found. Only significant differences have been observed when the variables ""cranberry treatment"" and ""dwell time of JJ catheter"" were related. ""Dwell time of JJ catheter"" was higher in patients with UTI (35.9 compared 28.5 days [P=.03]). UTI percentage was lower in cranberry supplemented patient group (12.9 compared to 38.7% [P=.04]).
CONCLUSIONS: We can conclude that American cranberry (120 mg) has an adjuvant effect in the prevention of UTI in patients with JJ catheter after surgery.
Abstract: Cranberry consumption has shown prophylactic effects against urinary tract infections (UTI), although the mechanisms involved are not completely understood. In this paper, cranberry phenolic compounds and their potential microbial-derived metabolites (such as simple phenols and benzoic, phenylacetic and phenylpropionic acids) were tested for their capacity to inhibit the adherence of uropathogenic Escherichia coli (UPEC) ATCC53503TM to T24 epithelial bladder cells. Catechol, benzoic acid, vanillic acid, phenylacetic acid and 3,4-dihydroxyphenylacetic acid showed anti-adhesive activity against UPEC in a concentration-dependent manner from 100-500 micro M, whereas procyanidin A2, widely reported as an inhibitor of UPEC adherence on uroepithelium, was only statistically significant (p < 0.05) at 500 micro M (51.3% inhibition). The results proved for the first time the anti-adhesive activity of some cranberry-derived phenolic metabolites against UPEC in vitro, suggesting that their presence in the urine could reduce bacterial colonization and progression of UTI.
Abstract: Urinary tract infection (UTI) is the most common infection
among nursing home residents, and the microorganisms pre-valent in this setting pose significant challenges for treatment. Cranberries (Vaccinium macrocarpon Aiton
) are thought to reduce UTIs; this view is supported by a placebo-controlled trial showing lower rates of bacteriuria plus pyuria with daily ingestion of 300 mL of cranberry juice cocktail (15.0% versus 28.1% in controls). However, subsequent studies of cranberries for prevention of UTI, including a large Cochrane meta-analysis, have shown mixed results. Various mechanisms of the bacteriologic effect of cranberries are postulated; however, inhibition of P fimbriae–mediated adhesion of E. coli by proanthocyanidin (PAC) remains the leading theory.
We sought to compare antibiotic susceptibility and proportions of non–E. coli Enterobacteriaceae among Gram-negative urinary isolates from participants randomized to cranberry capsules compared to placebo.
Abstract: Lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia increase with age. To date, several medications are available to treat LUTS, including herbal remedies which offer less side effects but lack robust efficacy studies.
This 6-month, randomized, double-blind, placebo-controlled study aimed at evaluating the dose effect of 250 or 500 mg cranberry powder (Flowens™) on LUTS and uroflowmetry in men over the age of 45. A total of 124 volunteers with PSA levels <2.5 ng/mL and an international prostate symptoms score (IPSS) score ≥8 were recruited and randomized. The primary outcome measure was the IPSS, evaluated at 3 and 6 months. Secondary outcome measures included quality of life, bladder volume (Vol), maximum urinary flow rate (Q max), average urinary flow rate (Q ave), ultrasound-estimated post-void residual urine volume (PVR), serum prostate-specific antigen, selenium, interleukin 6, and C-reactive protein at 6 months.
After 6 months, subjects in both Flowens™ groups had a lower IPSS (-3.1 and -4.1 in the 250- and 500-mg groups, p = 0.05 and p < 0.001, respectively) versus the placebo group (-1.5), and a dose-response effect was observed. There were significant differences in Q max, Q ave, PVR, and Vol in the Flowens™ 500-mg group versus baseline (p < 0.05). A dose-dependent effect on Vol was observed, as well as on PVR, for participants with a nonzero PVR. There was no effect on clinical chemistry or hematology markers.
Flowens™ showed a clinically relevant, dose-dependent, and significant reduction in LUTS in men over 45.
Abstract: OBJECTIVE: The risk of urinary tract infection (UTI) among women undergoing elective gynecological surgery during which a catheter is placed is high: 10-64% following catheter removal. We conducted the first randomized, double-blind, placebo-controlled trial of the therapeutic efficacy of cranberry juice capsules in preventing UTI after surgery.
STUDY DESIGN: We recruited patients from a single hospital between August 2011 and January 2013. Eligible participants were undergoing elective gynecological surgery that did not involve a fistula repair or vaginal mesh removal. One hundred sixty patients were randomized and received 2 cranberry juice capsules 2 times a day, equivalent to 2 8 ounce servings of cranberry juice, for 6 weeks after surgery or matching placebo. The primary endpoint was the proportion of participants who experienced clinically diagnosed and treated UTI with or without positive urine culture. Kaplan-Meier plots and log rank tests compared the 2 treatment groups.
RESULTS: The occurrence of UTI was significantly lower in the cranberry treatment group compared with the placebo group (15 of 80 [19%] vs 30 of 80 [38%]; odds ratio, 0.38; 95% confidence interval, 0.19-0.79; P = .008). After adjustment for known confounders, including the frequency of intermittent self-catheterization in the postoperative period, the protective effects of cranberry remained (odds ratio, 0.42; 95% confidence interval, 0.18-0.94). There were no treatment differences in the incidence of adverse events, including gastrointestinal upset (56% vs 61% for cranberry vs placebo).
CONCLUSION: Among women undergoing elective benign gynecological surgery involving urinary catheterization, the use of cranberry extract capsules during the postoperative period reduced the rate of UTI by half.
Abstract: OBJECTIVE: Cranberry extracts have been tested as a nutritional supplementation in the prevention of recurrent lower-urinary tract infections (R-UTIs), with mixed results. This pilot, registry study evaluates the prophylactic effects of oral supplementation with a new well-standardized cranberry extract in patients with R-UTI, over a 2-month follow-up.
PATIENTS AND METHODS: All subjects were suggested to take one capsule containing a cranberry extract (AnthocranTM) for 60 days and were also given lifestyle advice. Clinical outcomes were compared between patients on cranberry extracts and those who don't take this supplementation.
RESULTS: In total, 22 subjects completed the study in each of the two groups. In the cranberry group, the reduction in the frequency of UTI episodes during the study period compared with the two months before the inclusion was 73.3% (p < 0.05). This figure was 15.4% in the control group (p < 0.05; p = 0.012 vs cranberry group). Seven (31.8%) subjects in the cranberry group were symptom-free; no patient was symptom-free in the control group (p < 0.05). The mean duration of UTI episodes was 2.5 +/- 1.3 days in the cranberry group, compared with 3.6 +/- 1.7 days in subjects not on cranberry (p < 0.05). Three subjects (13.6%) in the cranberry group and 8 (36.3%) in the control group required medical consultation for UTI symptoms (p < 0.05). Urine evaluation was completely negative in 20/22 subjects in the Cranberry group (90.9%) and in 11 control subjects (50.0%; p < 0.005). No adverse events were observed.
CONCLUSIONS: These preliminary results, obtained in a field-practice setting, indicates the effectiveness and safety of a well-standardized cranberry extract in the prevention of R-UTI.
Abstract: Cranberry juice has been recognized as a treatment for urinary tract infections on the basis of scientific reports of proanthocyanidin anti-adhesion activity against Escherichia coli as well as from folklore. Xyloglucan oligosaccharides were detected in cranberry juice and the residue remaining following commercial juice extraction that included pectinase maceration of the pulp. A novel xyloglucan was detected through tandem mass spectrometry analysis of an ion at m/z 1055 that was determined to be a branched, three hexose, four pentose oligosaccharide consistent with an arabino-xyloglucan structure. Two-dimensional nuclear magnetic resonance spectroscopy analysis provided through-bond correlations for the alpha-l-Araf (1->2) alpha-d-Xylp (1->6) beta-d-Glcp sequence, proving the S-type cranberry xyloglucan structure. Cranberry xyloglucan-rich fractions inhibited the adhesion of E. coli CFT073 and UTI89 strains to T24 human bladder epithelial cells and that of E. coli O157:H7 to HT29 human colonic epithelial cells. SSGG xyloglucan oligosaccharides represent a new cranberry bioactive component with E. coli anti-adhesion activity and high affinity for type 1 fimbriae.
Abstract: The objective of this study was to determine the in-vitro and in-vivo activity of cranberry extracts against Escherichia coli O157:H7. This strain of E. coli was the most common etiologic agent of urinary tract infections isolated from patients. Filter sterilized aqueous and methanol extract of cranberry was prepared and used in the present study. The aqueous extract of cranberry produced inhibition zone ranging from (10.8-23.8) mm against the tested bacteria. While the methanol extract produces larger zones of inhibition (12.1-24.2) mm against the bacteria. The minimum inhibitory concentration (MIC) for the methanol and aqueous extract was 0.35 and 0.625 mg/ml, respectively. In vivo study involved inducing UTI in rats and then treated with (200 mg/kg B.W) aqueous and methanol extract and compared with Gentamicin treatment at a dose of (2 mg/kg B.W) subcutaneously for 14 days. Methanol extract succeeded in treated UTI caused by Escherichia coli in the infected rats and prevented infection comparing with aqueous extract and Gentamicin. Food, water intake, body weight, pH and creatinine level returned to normal values after treatment with methanol extract of Cranberry fruit (200 mg/Kg.B.W) comparing with aqueous extract of Cranberry fruit and 2 mg/Kg.B.W. of Gentamicin. These parameters used in this current study as indicator for curing from infection. These findings indicated that cranberry extract was effective at all levels in inhibiting E. coli O157:H7; thus it possesses antimicrobial activity and hold great promise as an antimicrobial agent.
Abstract: With the prevalence of inflammatory bowel disease (IBD) and its associated risk for development of colorectal cancer, it is of great importance to prevent and treat IBD. However, due to the complexity of etiology and potentially serious adverse effects, treatment options for IBD are relatively limited. Thus, the purpose of this study was to identify a safe food-based approach for the prevention and treatment of IBD. In this study, we tested the effects of cranberry products on preventing dextran sulphate sodium-induced murine colitis. Our results suggest that both cranberry extract and dried cranberries-fed groups had a significantly reduced disease activity index, where dried cranberries were more effective in preventing colitis than cranberry extract. Shortening of colon length, colonic myeloperoxidase activity and production of pro-inflammatory cytokines were attenuated in animals fed dried cranberries compared to the controls. The current report suggests that cranberries can be applied to prevent and reduce the symptoms of IBD.
Abstract: PURPOSE: Acute radiation cystitis, inflammation of the bladder, is a common side effect in men receiving external beam radiation for prostate cancer. Although several treatments provide symptomatic relief, there is no effective treatment to prevent or treat radiation cystitis. Cranberry products have been associated with urinary tract health. This study aimed to determine the effect of highly standardized cranberry capsules (containing 72 mg proanthocyanidins [PACS]) compared with that of placebo capsules on the incidence and severity of radiation cystitis.
METHODS: Forty-one men with prostate cancer participated in a double blinded randomized placebo controlled study. Men took one capsule a day at breakfast during treatment and for 2 weeks after treatment completion. Severity of urinary symptoms and the bother these caused were measured using the individual items of the urinary domain of the Modified Expanded Prostate Index Composite (EPIC).
RESULTS: The incidence of cystitis was lower in men taking cranberry capsules (65%) compared with those that took placebo capsules (90%) (p=0.058); severe cystitis was seen in 30% of men in the cranberry arm and 45% in the placebo arm (p=0.30). Overall, the incidence of pain/burning was significantly lower in the cranberry cohort (p=0.045). Men on the low hydration regimen who took cranberry had less pain/burning (p=0.038), stronger urine steam (p=0.030) and used significantly fewer pads/liners (p=0.042), which was significantly different from those on the high hydration regimen (p=0.028).
CONCLUSION: Men receiving radiation therapy for prostate cancer may benefit from using cranberry capsules, particularly those on low hydration regimens or with baseline urinary symptoms.
Abstract: OBJECTIVE: Our aim was to assess the usefulness of cranberry extract in multiple sclerosis (MS) patients suffering from urinary disorders.
METHODS: In total, 171 adult MS outpatients with urinary disorders presenting at eight centers were randomized (stratification according to center and use of clean intermittent self-catheterization) to cranberry versus placebo in a 1-year,
prospective, double-blind study that was analyzed using a sequential method on an intent-to-treat basis. An independent monitoring board analyzed the results of the analyses each time 40 patients were assessed on the main endpoint. Cranberry extract (36 mg proanthocyanidins per day) or a matching placebo was taken by participants twice daily for 1 year. The primary endpoint was the time to first symptomatic urinary tract infection (UTI), subject to validation by a validation committee.
RESULTS: The second sequential analyses allowed us to accept the null hypothesis (no difference between cranberry and placebo). There was no difference in time to first symptomatic UTI distribution across 1 year, with an estimated hazard ratio
of 0.99, 95% CI [0.61, 1.60] (p = 0.97). Secondary endpoints and tolerance did not differ between groups.
CONCLUSION: Taking cranberry extract versus placebo twice a day did not prevent UTI occurrence in MS patients with urinary disorders. Trial Registration NCT00280592.
Abstract: BACKGROUND: Urinary tract infections (UTIs) are the most common bacterial infection in women. Most UTIs are acute uncomplicated cystitis caused by Escherichia coli (86%). This study was undertaken to assess the effectiveness of an association of a cranberry dry extract, D-mannose, a gelling complex composed of the exopolysaccharides produced by Streptococcus thermophilus ST10 (DSM 25246) and tara gum, as well as the 2 microorganisms Lactobacillus plantarum LP01 (LMG P-21021) and Lactobacillus paracasei LPC09 (DSM 24243) in women affected by acute uncomplicated cystitis.
MATERIALS AND METHODS: Thirty-three premenopausal, nonpregnant women diagnosed with acute uncomplicated cystitis were enrolled in a pilot prospective study and
completed the treatment protocol. Subjects were instructed to take 2 doses per day during the first month, and then to continue with 1 sachet per day until the sixtieth day. Nitrites and leukocyte esterase on urine dipstick testing were used
as indicators of cystitis, with analysis performed at enrollment, after 30 and 60 days, and after 1 month of follow-up. Typical UTI symptoms, namely dysuria, frequent voiding of small volumes, urinary urgency, suprapubic pain, and gross
hematuria were scored 0 to 3 and evaluated at each visit.
RESULTS: Positive results for the presence of nitrites and leukocyte esterase were found in 14 and 20 subjects after 30 days and in 9 and 14 women after 60 days, respectively (P<0.001). At the end of the follow-up period, positive
results for nitrites and leukocyte esterase were recorded in only 4 and 3 of 24 and 19 subjects (16.7%, P=0.103; 15.8%, P=0.325, respectively), with negative results after 60 days. Typical symptoms of cystitis, specifically dysuria, frequent voiding, urgency, and suprapubic pain were significantly improved as well. No significant differences were recorded in the incidence and severity of hematuria at any visit.
CONCLUSION: The long-term ability of an association of cranberry, D-mannose, an innovative gelling complex, and the 2 microorganisms tested to significantly improve the uncomfortable symptoms reported by women with acute cystitis has been suggested.
Abstract: Urinary tract infections (UTIs) are among the most common bacterial infections affecting women. UTIs are primarily caused by Escherichia coli, which increases the likelihood of a recurrent infection. We encountered two cases of recurrent
UTIs (rUTIs) with a positive E. coli culture, not improving with antibiotics due to the development of antibiotic resistance. An alternative therapeutic regimen based on parsley and garlic, L-arginine, probiotics, and cranberry tablets has been given. This regimen showed a significant health improvement and symptoms relief without recurrence for more than 12 months. In conclusion, the case supports the concept of using alternative medicine in treating rUTI and as a prophylaxis or in patients who had developed antibiotic resistance.
Abstract: The purpose of this research was to correlate daily consumption of cranberry juice and symptoms of a diagnosed UTI among 26 volunteer adult female patients
Abstract: Pseudomonas aeruginosa colonizes the lungs in cystic fibrosis (CF) and mechanically ventilated patients by binding to the cellular receptors on the surface of the lung epithelium. Studies have shown that blocking this interaction could be achieved with sub-minimum inhibitory concentrations of antibiotics such as ciprofloxacin. The development of bacterial resistance is a probable drawback of such an intervention. The use of natural extracts to interfere with bacterial adhesion and invasion has recently gained substantial attention and is
hypothesized to inhibit bacterial binding and consequently prevent or reduce pathogenicity. This study used an A549 lung epithelial cell infection model, and the results revealed that a combination of aqueous cranberry extract with ciprofloxacin could completely prevent the adhesion and invasion of P. aeruginosa PAO1 compared to the untreated control. All of the natural extracts (cranberry, dextran, and soybean extracts) and ciprofloxacin showed a significant reduction (P<0.0001) in P. aeruginosa PAO1 adhesion to and invasion of lung epithelial
cells relative to the control. The cranberry, dextran, and soybean extracts could substantially increase the anti-adhesion and anti-invasion effects of ciprofloxacin to the averages of 100% (P<0.0001), 80% (P<0.0001), and 60%
(P<0.0001), respectively. Those extracts might result in a lower rate of the development of bacterial resistance; they are relatively safe and inexpensive agents, and utilizing such extracts, alone or in combination with ciprofloxacin,
as potential anti-adhesion and anti-invasion remedies, could be valuable in preventing or reducing P. aeruginosa lung infections.
Abstract: SCOPE: A major portion of ingested procyanidins is degraded by human microbiota in the colon into various phenolic compounds. These microbial metabolites are thought to contribute to the health benefits of procyanidins in vivo. The
objective of this study was to identify and quantify the microbial metabolites of procyanidins after anaerobic fermentation with human microbiota.
METHODS AND RESULTS: (-)-Epicatechin, (+)-catechin, procyanidin B2, procyanidin A2, partially purified apple and cranberry procyanidins were incubated with human
microbiota at a concentration equivalent to 0.5 mM epicatechin. GC-MS analysis showed that common metabolites of all six substrates were benzoic acid, 2-phenylacetic acid, 3-phenylpropionic acid, 2-(3'-hydroxyphenyl)acetic acid,
2-(4'-hydroxyphenyl)acetic acid, 3-(3'-hydroxyphenyl)propionic acid, and hydroxyphenylvaleric acid. 5-(3',4'-Dihydroxyphenyl)-γ-valerolactones and 5-(3'-hydroxyphenyl)-γ-valerolactones were identified as the microbial metabolites of epicatechin, catechin, procyanidin B2, and apple procyanidins but not from the procyanidin A2 or cranberry procyanidin ferments. 2-(3',4'-Dihydroxyphenyl)acetic acid was only found in the fermented broth of procyanidin B2, A2, apple, and cranberry procyanidins. The mass recoveries of microbial metabolites range from 20.0 to 56.9% for the six substrates after 24 h
CONCLUSION: Procyanidins, both B-type and A-type can be degraded by human gut microbiota. The microbial metabolites may contribute to the bioactivities of procyanidins.
Abstract: In the present study, the efficacy of generally recognised as safe (GRAS) antimicrobial plant metabolites in regulating the growth of Staphylococcus aureus and S. epidermidis was investigated. Thymol, carvacrol and eugenol showed the
strongest antibacterial action against these microorganisms, at a subinhibitory concentration (SIC) of ≤ 50 μg ml(-1). Genistein, hydroquinone and resveratrol showed antimicrobial effects but with a wide concentration range (SIC = 50-1,000 μg ml(-1)), while catechin, gallic acid, protocatechuic acid, p-hydroxybenzoic acid and cranberry extract were the most biologically compatible molecules (SIC ≥ 1000 μg ml(-1)). Genistein, protocatechuic acid, cranberry extract, p-hydroxybenzoic acid and resveratrol also showed anti-biofilm activity against S. aureus, but not against S. epidermidis in which, surprisingly, these metabolites stimulated biofilm formation (between 35% and 1,200%). Binary combinations of cranberry extract and resveratrol with genistein, protocatechuic or p-hydroxibenzoic acid enhanced the stimulatory effect on S. epidermidis biofilm formation and maintained or even increased S. aureus anti-biofilm
Abstract: Despite considerable controversy about their effects, cranberries in various forms have been used widely for several decades to prevent as well as treat urinary tract infections (UTIs). The purpose of this article is to present a review of research-based information regarding the ability of cranberries to prevent UTIs in adults at risk for UTIs. Current evidence suggests that cranberries decrease bacterial adherence to uroepithelial cells and thus decrease
the incidence of UTIs without adverse effects in most individuals. Thus clinicians may safely advise patients that cranberries are helpful in preventing UTIs. Cranberries may be a viable adjunct to antibiotics for patients with repeated UTIs.
Abstract: Urinary tract infections (UTIs) are relatively common in women and may be classified as uncomplicated or complicated, depending upon the urinary tract anatomy and physiology. Acute uncomplicated cystitis (AUC) occurs when urinary pathogens from the bowel or vagina colonize the periurethral mucosa and reach the bladder. The vast majority of episodes in healthy women involving the same bacterial strain that caused the initial infection are thought to be reinfections. About 90% of AUC are caused by uropathogenic Escherichia coli (UPEC), but Proteus mirabilis also plays an important role. Several studies support the importance of cranberry (Vaccinium macrocarpon) proanthocyanidins in preventing adhesion of P-fimbriated UPEC to uroepithelial cells. In this study, we evaluated the in vitro anti-adhesion activity of A2-linked proanthocyanidins from cranberry on a UPEC and Proteus mirabilis strains and their possible influence on urease activity of the latter. A significant reduction of UPEC adhesion (up to 75%) on the HT1376 cell line was observed vs. control. For the strains of P. mirabilis there was also a reduction of adhesion (up to 75%) compared to controls, as well as a reduction in motility and urease activity. These results suggest that A2-type cranberry proanthocyanidins could aid in maintaining urinary tract health.
Abstract: BACKGROUND & OBJECTIVES: Emergence of antimicrobial resistance in Pseudomonas aeruginosa has led to the search for alternative agents for infections control. Natural products have been a good alternative to present antibiotics. The present study was undertaken to evaluate the effectiveness of cranberry in attenuation of virulence of P. aeruginosa in experimental urinary tract infection (UTI) in mouse model. Efforts were also directed to explore the action of cranberry towards virulence of P. aeruginosa through quorum sensing (QS) inhibition.
METHODS: Efficacy of cranberry was evaluated in an experimental UTI mouse model and on production of QS signals, alginate, pyochelin, haemolysin, phospholipase-C, cell-surface hydrophobicity, uroepithelial cell-adhesion assay and biofilm formation by already standardized methods.
RESULTS: Presence of cranberry showed significant decline in the production of QS signals, biofilm formation and virulence factors of P. aeruginosa in vitro (P<0.001). Further, cranberry was found to be useful in prevention of experimental UTI in mouse model as indicated by reduced renal bacterial colonization and kidney tissues destruction.
INTERPRETATION & CONCLUSIONS: The findings of the present study indicated that cranberry inhibited QS and hence elaboration of virulence factors of P. aeruginosa. It also affected the adherence ability of this pathogen. This approach can lead to the discovery of new category of safe anti-bacterial drugs from dietary sources such as cranberry with reduced toxicity without the risk of antibiotic resistance.
Abstract: Consumption of polyphenol-rich foods is associated with lower risk from many chronic diseases. We hypothesized that a single dose of cranberry beverage would improve indices of oxidative stress, inflammation, and urinary antibacterial adhesion activity in healthy humans. Six males and 6 females (18-35 years; body mass index, 19-25 kg/m(2)) consumed placebo, cranberry leaf extract beverage, or low-calorie cranberry juice cocktail (LCJC) once in a randomized, double-blind, placebo-controlled cross-over experimental design trial. The washout period between beverages was 1 week. Blood was collected 0, 2, 4, 8, and 24 hours after beverage consumption for measuring oxidative and inflammatory biomarkers. Urine was collected at 0, 0 to 3, 3 to 6, 6 to 9, 9 to 12, and 24 hours postintervention to assess antibacterial adhesion activity. Consumption of cranberry leaf extract beverage elevated (P < .05) blood glutathione peroxidase activity, whereas LCJC consumption increased (P < .05) glutathione concentrations and superoxide dismutase activity compared with placebo. Cranberry leaf extract beverage and LCJC consumption had no effect on the inflammatory biomarkers measured as compared with placebo. At 0 to 3 hours postconsumption, urine from participants who consumed cranberry beverages had higher (P < .05) ex vivo antiadhesion activity against P-fimbriated Escherichia coli compared with placebo. An acute dose of cranberry beverages improved biomarkers of antioxidant status and inhibition of bacterial adhesion in urine. Copyright 2014 Elsevier Inc. All rights reserved.
Abstract: BACKGROUND: Urinary tract infections (UTIs) are common and result in an enormous economic burden. The increasing prevalence of antibiotic-resistant microorganisms has stimulated interest in non-antibiotic agents to prevent UTIs.
OBJECTIVE: To evaluate the cost-effectiveness of cranberry prophylaxis compared to antibiotic prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) over a 12 month period in premenopausal women with recurrent UTIs.
MATERIALS AND METHODS: An economic evaluation was performed alongside a randomized trial. Primary outcome was the number of UTIs during 12 months. Secondary outcomes included satisfaction and quality of life. Healthcare utilization was measured using questionnaires. Missing data were imputed using multiple imputation. Bootstrapping was used to evaluate the cost-effectiveness of the treatments.
RESULTS: Cranberry prophylaxis was less effective than TMP-SMX prophylaxis, but the differences in clinical outcomes were not statistically significant. Costs after 12 months in the cranberry group were statistically significantly higher than in the TMP-SMX group (mean difference 249, 95% confidence interval 70 to 516). Cost-effectiveness planes and cost-effectiveness acceptability curves showed that cranberry prophylaxis to prevent UTIs is less effective and more expensive than (dominated by) TMP-SMX prophylaxis.
CONCLUSION: In premenopausal women with recurrent UTIs, cranberry prophylaxis is not cost-effective compared to TMP-SMX prophylaxis. However, it was not possible to take into account costs attributed to increased antibiotic resistance within the framework of this randomized trial; modeling studies are recommended to investigate these costs. Moreover, although we based the dosage of cranberry extract on available evidence, this may not be the optimal dosage. Results may change when this optimal dosage is identified.
Abstract: OBJECTIVES: To investigate whether the preventive use of cranberry capsules in long-term care facility (LTCF) residents is cost-effective depending on urinary tract infection (UTI) risk. DESIGN: Economic evaluation with a randomized controlled trial. SETTING: Long-term care facilities. PARTICIPANTS: LTCF residents (N=928, 703 female, median age 84), stratified according to UTI risk. MEASUREMENTS: UTI incidence (clinically or strictly defined), survival, quality of life, quality-adjusted life years (QALYs), and costs. RESULTS: In the weeks after a clinical UTI, participants showed a significant but moderate deterioration in quality of life, survival, care dependency, and costs. In high-UTI-risk participants, cranberry costs were estimated at Euro 439 per year (1.00 euro=1.37 U.S. dollar), which is Euro 3,800 per prevented clinically defined UTI (95% confidence interval=Euro 1,300-infinity). Using the strict UTI definition, the use of cranberry increased costs without preventing UTIs. Taking cranberry capsules had a 22% probability of being cost-effective compared with placebo (at a willingness to pay of Euro 40,000 per QALY). In low-UTI-risk participants, use of cranberry capsules was only 3% likely to be cost-effective. CONCLUSION: In high-UTI-risk residents, taking cranberry capsules may be effective in preventing UTIs but is not likely to be cost-effective in the investigated dosage, frequency, and setting. In low-UTI-risk LTCF residents, taking cranberry capsules twice daily is neither effective nor cost-effective.
Cranberries have been used widely for several decades for the prevention and treatment of urinary tract infections (UTIs). This is the third update of our review first published in 1998 and updated in 2004 and 2008.
To assess the effectiveness of cranberry products in preventing UTIs in susceptible populations.
We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL in The Cochrane Library) and the Internet. We contacted companies involved with the promotion and distribution of cranberry preparations and checked reference lists of review articles and relevant studies.Date of search: July 2012
All randomised controlled trials (RCTs) or quasi-RCTs of cranberry products for the prevention of UTIs.
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) were calculated where appropriate, otherwise a narrative synthesis was undertaken. Quality was assessed using the Cochrane risk of bias assessment tool.
This updated review includes a total of 24 studies (six cross-over studies, 11 parallel group studies with two arms; five with three arms, and two studies with a factorial design) with a total of 4473 participants. Ten studies were included in the 2008 update, and 14 studies have been added to this update. Thirteen studies (2380 participants) evaluated only cranberry juice/concentrate; nine studies (1032 participants) evaluated only cranberry tablets/capsules; one study compared cranberry juice and tablets; and one study compared cranberry capsules and tablets. The comparison/control arms were placebo, no treatment, water, methenamine hippurate, antibiotics, or lactobacillus. Eleven studies were not included in the meta-analyses because either the design was a cross-over study and data were not reported separately for the first phase, or there was a lack of relevant data. Data included in the meta-analyses showed that, compared with placebo, water or not treatment, cranberry products did not significantly reduce the occurrence of symptomatic UTI overall (RR 0.86, 95% CI 0.71 to 1.04) or for any the subgroups: women with recurrent UTIs (RR 0.74, 95% CI 0.42 to 1.31); older people (RR 0.75, 95% CI 0.39 to 1.44); pregnant women (RR 1.04, 95% CI 0.97 to 1.17); children with recurrent UTI (RR 0.48, 95% CI 0.19 to 1.22); cancer patients (RR 1.15 95% CI 0.75 to 1.77); or people with neuropathic bladder or spinal injury (RR 0.95, 95% CI: 0.75 to 1.20). Overall heterogeneity was moderate (I² = 55%). The effectiveness of cranberry was not significantly different to antibiotics for women (RR 1.31, 95% CI 0.85, 2.02) and children (RR 0.69 95% CI 0.32 to 1.51). There was no significant difference between gastrointestinal adverse effects from cranberry product compared to those of placebo/no treatment (RR 0.83, 95% CI 0.31 to 2.27). Many studies reported low compliance and high withdrawal/dropout problems which they attributed to palatability/acceptability of the products, primarily the cranberry juice. Most studies of other cranberry products (tablets and capsules) did not report how much of the 'active' ingredient the product contained, and therefore the products may not have had enough potency to be effective.
Prior to the current update it appeared there was some evidence that cranberry juice may decrease the number of symptomatic UTIs over a 12 month period, particularly for women with recurrent UTIs. The addition of 14 further studies suggests that cranberry juice is less effective than previously indicated. Although some of small studies demonstrated a small benefit for women with recurrent UTIs, there were no statistically significant differences when the results of a much larger study were included. Cranberry products were not significantly different to antibiotics for preventing UTIs in three small studies. Given the large number of dropouts/withdrawals from studies (mainly attributed to the acceptability of consuming cranberry products particularly juice, over long periods), and the evidence that the benefit for preventing UTI is small, cranberry juice cannot currently be recommended for the prevention of UTIs. Other preparations (such as powders) need to be quantified using standardised methods to ensure the potency, and contain enough of the 'active' ingredient, before being evaluated in clinical studies or recommended for use.
Abstract: Epidemiologic studies indicate that millions of people suffer from recurrent cystitis, a pathology requiring antibiotic prophylaxis and entailing high social costs. Cranberry is a traditional folk remedy for cystitis and, which, in the form of a variety of products and formulations has over several decades undergone extensive evaluation for the management of urinary tract infections (UTI). The aim of this retrospective study is to summarize and review the most relevant and recent preclinical and clinical studies on cranberries for the treatment of UTIs. The scientific literature selected for this review was identified by searches of Medline via PubMed. A variety of recent experimental evidence has shed light on the mechanism underlying the anti-adhesive properties of proanthrocyanidins, their structure-activity relationships, and pharmacokinetics. Analysis of clinical studies and evaluation of the cranberry efficacy/safety ratio in the prevention of UTIs strongly support the use of cranberry in the prophylaxis of recurrent UTIs in young and middle-aged women. However, evidence of its clinical use among other patients remains controversial.
Abstract: OBJECTIVES: Candida albicans is a common cause of nosocomial urinary tract infections (UTIs) and is responsible for increased morbidity and healthcare costs. Moreover, the US Centers for Medicare & Medicaid Services no longer reimburse for hospital-acquired catheter-associated UTIs. Thus, development of specific approaches for the prevention of Candida urinary infections is needed. Cranberry juice-derived proanthocyanidins (PACs) have efficacy in the prevention of bacterial UTIs, partially due to anti-adherence properties, but there are limited data on their use for the prevention and/or treatment of Candida UTIs. Therefore, we sought to systematically assess the in vitro effect of cranberry-derived PACs on C. albicans biofilm formation in artificial urine.
METHODS: C. albicans biofilms in artificial urine were coincubated with cranberry PACs at serially increasing concentrations and biofilm metabolic activity was assessed using the XTT assay in static microplate and silicone disc models.
RESULTS: Cranberry PAC concentrations of >16 mg/L significantly reduced biofilm formation in all C. albicans strains tested, with a paradoxical effect observed at high concentrations in two clinical isolates. Further, cranberry PACs were additive in combination with traditional antifungals. Cranberry PACs reduced C. albicans adherence to both polystyrene and silicone. Supplementation of the medium with iron reduced the efficacy of cranberry PACs against biofilms.
CONCLUSIONS: These findings indicate that cranberry PACs have excellent in vitro activity against C. albicans biofilm formation in artificial urine. We present preliminary evidence that cranberry PAC activity against C. albicans biofilm formation is due to anti-adherence properties and/or iron chelation.
Abstract: OBJECTIVES: To determine whether cranberry capsules prevent urinary tract infection (UTI) in long-term care facility (LTCF) residents. DESIGN: Double-blind randomized placebo-controlled multicenter trial. SETTING: Long-term care facilities (LTCFs). PARTICIPANTS: LTCF residents (N=928; 703 women, median age 84). MEASUREMENTS: Cranberry and placebo capsules were taken twice daily for 12 months. Participants were stratified according to UTI risk (risk factors included long-term catheterization, diabetes mellitus, >=1 UTI in preceding year). Main outcomes were incidence of UTI according to a clinical definition and a strict definition. RESULTS: In participants with high UTI risk at baseline (n=516), the incidence of clinically defined UTI was lower with cranberry capsules than with placebo (62.8 vs 84.8 per 100 person-years at risk, P=.04); the treatment effect was 0.74 (95% confidence interval (CI)=0.57-0.97). For the strict definition, the treatment effect was 1.02 (95% CI=0.68-1.55). No difference in UTI incidence between cranberry and placebo was found in participants with low UTI risk (n=412). CONCLUSION: In LTCF residents with high UTI risk at baseline, taking cranberry capsules twice daily reduces the incidence of clinically defined UTI, although it does not reduce the incidence of strictly defined UTI. No difference in incidence of UTI was found in residents with low UTI risk.
Abstract: Despite cranberry being associated with the prevention of bacterial infections for over a century, our understanding of the bioavailability and mechanisms by which cranberry prevents infection is limited. This study investigates the interactions between cranberry proanthocyanidins (CPAC) and human serum proteins (albumin, alpha-1-acid glycoprotein, and fibrinogen) that may be encountered during CPAC metabolism following ingestion. To better understand how CPAC might interfere with bacterial infection, we also examined the interactions between CPAC and selected bacterial virulence factors; namely, lipopolysaccharide (LPS) and rhamnolipid. The binding of CPAC to the serum proteins, rhamnolipids and LPS from Escherichia coli O111:B4 can be described by Langmuir-type isotherms, allowing the determination of the apparent adsorption affinity constants, with CPAC interacting most strongly with fibrinogen with a binding constant of 2.2 x 10(8) M(-1). These binding interactions will limit the bioavailability of the CPAC at the site of action, an important consideration in designing further clinical trials. Furthermore, CPAC interacts with Pseudomonas aeruginosa 10 LPS, E. coli O111:B4 LPS, and P. aeruginosa rhamnolipids in fundamentally different manners, supporting the theory that cranberry prevents bacterial infections via multiple mechanisms.
Abstract: Cranberry juice polyphenols have gained importance over the past decade due to their promising health benefits. The bioactive component, proanthocyanidins is mainly responsible for its protective effect. A lot has been said about its role in urinary tract infection and other systemic diseases, but little is known about its oral benefits. An extensive search was carried out in the PubMed database using the terms "cranberry polyphenols" and "periodontitis" together. The institute library was also thoroughly scrutinized for all relevant information. Thus, a paper was formulated, the aim of which was to review the role of high molecular weight cranberry fraction on oral tissues and periodontal diseases.
Abstract: 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.
Abstract: Gut colonization by extra-intestinal pathogenic Escherichia coli (ExPEC) increases the risk of subsequent infections, including urinary tract infection and septicemia. Previous work suggests that cranberry proanthocyanidins (PAC) interact with bacterial surface factors, altering bacterial interaction with host cells. Methods were developed to determine if ratios of "A-type" to "B-type" interflavan bonds in PAC affect ExPEC agglutination and invasion of enterocytes. In cranberries, 94.5% of PAC contain one or more "A-type" bonds, whereas in apples, 88.3% of PAC contain exclusively "B-type" bonds. Results show that cranberry "A-type" PAC have greater bioactivity than apple "B-type" PAC for increasing ExPEC agglutination and decreasing ExPEC epithelial cell invasion.
Abstract: BACKGROUND: Recurrent urinary tract infections (UTIs) are a common problem among women. However, comparative effectiveness strategies for managing recurrent UTIs are lacking.
METHODS: We performed a systematic literature review of management of women experiencing >3 UTIs per year. We then developed a Markov chain Monte Carlo model of recurrent UTI for each management strategy with >2 adequate trials published. We simulated a cohort that experienced 3 UTIs/year and a secondary cohort that experienced 8 UTIs/year. Model outcomes were treatment efficacy, patient and payer cost, and health-related quality of life.
RESULTS: Five strategies had >2 clinical trials published: (1) daily antibiotic (nitrofurantoin) prophylaxis; (2) daily estrogen prophylaxis; (3) daily cranberry prophylaxis; (4) acupuncture prophylaxis; and (5) symptomatic self-treatment. In the 3 UTIs/year model, nitrofurantoin prophylaxis was most effective, reducing the UTI rate to 0.4 UTIs/year, and the most expensive to the payer ($821/year). All other strategies resulted in payer cost savings but were less efficacious. Symptomatic self-treatment was the only strategy that resulted in patient cost savings, and was the most favorable strategy in term of cost per quality-adjusted life-year (QALY) gained.
CONCLUSIONS: Daily antibiotic use is the most effective strategy for recurrent UTI prevention compared to daily cranberry pills, daily estrogen therapy, and acupuncture. Cost savings to payers and patients were seen for most regimens, and improvement in QALYs were seen with all. Our findings provide clinically meaningful data to guide the physician-patient partnership in determining a preferred method of prevention for this common clinical problem.
Abstract: "PURPOSE: Plants extracts are used in urology to manage urinary tract infections. We aimed to evaluate the efficacy of a preparation with solidago, orthosiphon, birch and cranberry extracts (CISTIMEV PLUS()) in reducing microbial colonization and biofilm development in patients with indwelling urinary catheters.
METHODS: All consecutive outpatients attending our department between January and June 2010 for the substitution of indwelling catheters were considered for this single-blinded, randomized and controlled pilot study to test superiority of the preventative management (CISTIMEV PLUS(), 1 tablet daily for 30 days) in respect to no treatment. A sample size of 10-40 participants per group was considered adequate. All patients underwent urine culture the same day of the catheter substitution and were then randomized into test group (n = 48) and control group (n = 35). Ultrastructural analysis was also performed. After 30 days, the catheter was replaced and the analysis repeated. The primary outcome was the rate of positive urinary culture at the end of the entire study period.
RESULTS: Ten patients abandoned the study. At 30 days, according to per-protocol analysis, the groups statistically differed regarding the rate of positive urine cultures: test group 10/43 and control group 16/30 (p = 0.013) (-30.1 % [95 % CI -51.94 to -8.21]). The most common isolated bacteria were Escherichia coli and Enterococcus faecalis.
CONCLUSIONS: The use of solidago, orthosiphon, birch and cranberry extracts resulted in a significant reduction of microbial colonization in patients with indwelling urinary catheters. Larger clinical trials are needed to demonstrate that the effects here reported are sufficient to reduce symptomatic catheter-associated urinary tract infections."
Abstract: BACKGROUND: Urinary tract infections (UTIs) are one of the most common bacterial infections, and over 50% of women will have a UTI during their lifetimes. Antibiotics are used for prophylaxis of recurrent UTIs but can lead to emergence of drug-resistant bacteria. Therefore, it is reasonable to investigate nutritional strategies for prevention of UTIs. Cranberry juices and supplements have been used for UTI prophylaxis, but with variable efficacy. Because dried cranberries may contain a different spectrum of polyphenolics than juice, consuming berries may or may not be more beneficial than juice in decreasing the incidence of UTIs in susceptible women. The primary objectives of this study were to determine if consumption of sweetened, dried cranberries (SDC) decreases recurrent UTIs and whether this intervention would alter the heterogeneity, virulence factor (VF) profiles, or numbers of intestinal E. coli.
METHODS: Twenty women with recurrent UTIs were enrolled in the trial and consumed one serving of SDC daily for two weeks. Clinical efficacy was determined by two criteria, a decrease in the six-month UTI rates pre- and post-consumption and increased time until the first UTI since beginning the study. Strain heterogeneity and virulence factor profiles of intestinal E. coli isolated from rectal swabs were determined by DNA fingerprinting and muliplex PCR, respectively. The numbers of intestinal E. coli eluted from rectal swabs pre- and post-consumption were also quantified.
RESULTS: Over one-half of the patients did not experience a UTI within six months of SDC consumption, and the mean UTI rate per six months decreased significantly. Kaplan-Meier analysis of infection incidence in women consuming SDC compared to patients in a previous control group showed a significant reduction in time until first UTI within six months. The heterogeneity, VF profiles, and prevalence of intestinal E. coli strains were not significantly different after cranberry consumption.
CONCLUSIONS: Results of this study indicate a beneficial effect from consuming SDC to reduce the number of UTIs in susceptible women. Because there were no changes in the heterogeneity or VF profiles of E. coli, additional studies are needed to determine the mechanism of action of SDC for reduction of UTIs.
Abstract: Recent observational and clinical studies have raised interest in the potential health effects of cranberry consumption, an association that appears to be due to the phytochemical content of this fruit. The profile of cranberry bioactives is distinct from that of other berry fruit, being rich in A-type proanthocyanidins (PACs) in contrast to the B-type PACs present in most other fruit. Basic research has suggested a number of potential mechanisms of action of cranberry bioactives, although further molecular studies are necessary. Human studies on the health effects of cranberry products have focused principally on urinary tract and cardiovascular health, with some attention also directed to oral health and gastrointestinal epithelia. Evidence suggesting that cranberries may decrease the recurrence of urinary tract infections is important because a nutritional approach to this condition could lower the use of antibiotic treatment and the consequent development of resistance to these drugs. There is encouraging, but limited, evidence of a cardioprotective effect of cranberries mediated via actions on antioxidant capacity and lipoprotein profiles. The mixed outcomes from clinical studies with cranberry products could result from interventions testing a variety of products, often uncharacterized in their composition of bioactives, using different doses and regimens, as well as the absence of a biomarker for compliance to the protocol. Daily consumption of a variety of fruit is necessary to achieve a healthy dietary pattern, meet recommendations for micronutrient intake, and promote the intake of a diversity of phytochemicals. Berry fruit, including cranberries, represent a rich source of phenolic bioactives that may contribute to human health.
Abstract: Urinary tract infections (UTIs) represent a common and quite costly medical problem, primarily affecting the female population which may be due to a shorter urethra. The bacterium Escherichia coli are mainly responsible for most uncomplicated UTIs. Cranberry antibacterial effects have widely been studied in vitro, and laboratory and clinical studies have also been performed to elucidate the mechanisms of cranberry actions and the clinical benefits of cranberry consumption against UTIs. The present review aimed to summarize the proposed mechanisms of cranberry actions against UTIs and the clinical trials that evaluated the efficacy of supplementing cranberry products in different subpopulations. Taking into consideration the existing data, cranberry consumption may prevent bacterial adherence to uroepithelial cells which reduces the development of UTI. Cranberry consumption could also decreasing UTI related symptoms by suppressing inflammatory cascades as an immunologic response to bacteria invasion. The existing clinical trials suggest that the beneficial effects of cranberry against UTIs seem to be prophylactic by preventing the development of infections; however, they exert low effectiveness in populations at increased risk for contracting UTIs. Additional well-designed, double-blind, placebo-controlled clinical trials that use standardized cranberry products are strongly justified in order to determine the efficiency of cranberry on the prevention of UTIs in susceptible populations. Copyright 2013 Elsevier Inc. All rights reserved.
Abstract: BACKGROUND: The present study was aimed at determining the prophylactic efficacy of American cranberry (AC) extract (Cysticlean) in women with recurrent symptomatic postcoital urinary tract infections (PCUTI), non-consumer of AC extract in the past 3 months before inclusion, and to determine changes in their quality of life (QoL).
METHODS: This was a single center, observational, prospective study in a total of 20 women (mean age 35.2 years; 50.0% were married). Patients were followed up for 3 and 6 months during treatment.
RESULTS: The number of PCUTIs in the previous 3 months prior to start the treatment with Cysticlean was 2.8+1.3 and it was reduced to 0.2+0.5 at Month 6 (P<0.0001), which represent a 93% improvement. At baseline, the mean score on the VAS scale (range from 0 to 100) for assessing the QoL was 62.4+19.1, increasing to 78.2+12.4 at Month 6 (P=0.0002), which represents a 20% improvement. All patients had an infection with positive urine culture at baseline, after 6 months there were only 3 symptomatic infections (P<0.001). The most common bacterium was Escherichia coli.
CONCLUSIONS: Prophylaxis with American cranberry extract (Cysticlean) could be an alternative to classical therapies with antibiotics. Further studies are needed to confirm results obtained in this pilot study.
Abstract: The "A-type" proanthocyanidins in cranberry fruit (Vaccinium macrocarpon Ait.) are bioactive components associated with prevention of urinary tract infections (UTI). Cranberry juice, fruit (fresh and dried), functional foods, and cranberry dietary supplements are promoted for prevention of UTI and for maintenance of urinary tract health (UTH), on the basis of their content of cranberry proanthocyanidins (c-PAC) with "A-type" interflavan bonds. With increasing consumer use of cranberries for maintenance of UTH and an expanding number of commercial cranberry products of different types, the availability of unified methods for measuring levels of c-PAC is important. This review discusses quantitative and qualitative analysis of c-PAC with "A-type" interflavan bonds in relation to their biological activity for UTI prevention. The integrity (including authenticity, standardization, efficacy, and safety) of cranberry fruit, juices, and dietary supplements may now be measured by using recent advances in mass spectrometry, liquid chromatography, production of c-PAC standards, and improved simple quantitative techniques.
Abstract: Basic studies have proven that cranberries may prevent urinary tract infections through changing the adhesiveness of Escherichia coli (E. coli) to urothelial cells. Various cranberry preparations, including extract powder, capsules, and juice, have been shown to be effective in clinical and epidemiological research. Because cranberries are most commonly consumed as juice in a diluted concentration, the aim of this study was to investigate whether the equivalent daily dose of cranberry juice is sufficient to modify host urine to change the uropathogenicity of E. coli. Urine from rats taking an equivalent daily dose of cranberry juice has been shown to decrease the capability of E. coli in hemagglutination, urothelium adhesion, nematode killing, and biofilm formation. All these changes occurred after E. coli was incubated in cranberry metabolite-containing urine, defined as urine opsonization. Urine opsonization of E. coli resulted in 40.9% (p = 0.0038) decrease in hemagglutination ability, 66.7% (p = 0.0181) decrease in urothelium adhesiveness, 16.7% (p = 0.0004) increase in the 50% lethal time in killing nematodes, and 53.9% (p = 5.9 x 10(-4)) decrease in biofilm formation. Thus, an equivalent daily dose of cranberry juice should be considered sufficiently potent to demonstrate urine opsonization in E. coli.
Abstract: Recent observational and clinical studies have raised interest in the
potential health effects of cranberry consumption, an association that
appearsto be due to the phytochemical content of this fruit. The profile of
cranberry bioactives is distinct from that of other berry fruit, being
rich in A-type proanthocyanidins (PACs) in contrast to the B-type PACs present
in most other fruit. Basic research has suggested a number of potential
mechanisms of action of cranberry bioactives, although further molecular
studies are necessary. Human studies on the health effects of cranberry
products have focused principally on urinary tract and cardiovascular
health, with some attention also directed to oral health and
gastrointestinal epithelia. Evidence suggesting that cranberries may decrease the
recurrence of urinary tract infections is important because a nutritional
approach to this condition could lower the use of antibiotic treatment
and the consequent development of resistance to these drugs. There is
encouraging, but limited, evidence of a cardioprotective effect of
cranberries mediated via actions on antioxidant capacity and lipoprotein
profiles. The mixed outcomes from clinical studies with cranberry
products could result from interventions testing a variety of products,
often uncharacterized in their composition of bioactives, using different
doses and regimens, as well as the absence of a biomarker for compliance
to the protocol. Daily consumption of a variety of fruit is necessary to
achieve a healthy dietary pattern, meet recommendations for micronutrient
intake, and promote the intake of a diversity of phytochemicals. Berry
fruit, including cranberries, represent a rich source of phenolic bioactives
that may contribute to human health.
Abstract: We examined the rate of relapse, as a variable index, in patients with urinary tract infection (UTI) who suffered from multiple relapses when using cranberry juice (UR65). A randomized, placebo-controlled, double-blind study was conducted from October 2007 to September 2009 in Japan. The subjects were outpatients aged 20 to 79 years who were randomly divided into two groups. One group received cranberry juice (group A) and the other a placebo beverage (group P). To keep the conditions blind, the color and taste of the beverages were adjusted. The subjects drank 1 bottle (125 mL) of cranberry juice or the placebo beverage once daily, before going to sleep, for 24 weeks. The primary endpoint was relapse of UTI. In the group of females aged 50 years or more, there was a significant difference in the rate of relapse of UTI between groups A and P (log-rank test; p = 0.0425). In this subgroup analysis, relapse of UTI was observed in 16 of 55 (29.1 %) patients in group A and 31 of 63 (49.2 %) in group P. In this study, cranberry juice prevented the recurrence of UTI in a limited female population with 24-week intake of the beverage.
Abstract: Proteus mirabilis is an etiological agent of complicated urinary tract infections. North American cranberries (Vaccinium macrocarpon) have long been considered to have protective properties against urinary tract infections. This work reports the effects of cranberry powder (CP) on the motility of P. mirabilis HI4320 and its expression of flaA, flhD, and ureD. Our results show that swimming and swarming motilities and swarmer-cell differentiation were inhibited by CP. Additionally, transcription of the flagellin gene flaA and of flhD, the first gene of the flagellar master operon flhDC, decreased during exposure of P. mirabilis to various concentrations of CP. Moreover, using ureD-gfp, a fusion of the urease accessory gene ureD with gfp, we show that CP inhibits urease expression. Because we demonstrate that CP does not inhibit the growth of P. mirabilis, the observed effects are not attributable to toxicity. Taken together, our results demonstrate that CP hinders motility of P. mirabilis and reduces the expression of important virulence factors.
Abstract: As the beneficial effects of American cranberry (Vaccinium macrocarpon) can be partly attributed to its phenolic composition, the evaluation of the physiological behaviour of this fraction is crucial. A rapid and sensitive method by ultra-performance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) has been used to identify phenolic metabolites in human urine after a single dose of cranberry syrup. Prior to the analysis, metabolites were extracted using an optimised solid-phase extraction procedure. All possible metabolites were investigated based on retention time, accurate mass data and isotope and fragmentation patterns. Free coumaroyl hexose (isomer 1 and 2), dihydroxybenzoic acid, caffeoyl glucose, dihydroferulic acid 4-O--d-glucuronide, methoxyquercetin 3-O-galactoside, scopoletin, myricetin and quercetin, together with other 23 phase-I and phase-II metabolites, including various isomers, could be tentatively identified in the urine. Afterwards, the metabolites were simultaneously screened in the urine of different subjects at 0, 2, 4, and 6h after the ingestion of cranberry syrup by Target Analysis(TM) software.
Abstract: BACKGROUND: Cranberry fruits possess many biological activities partly due to their various phenolic compounds; however the underlying modes of action are poorly understood. We studied the effect of cranberry fruit extracts on the gene expression of Staphylococcus aureus to identify specific cellular processes involved in the antibacterial action.
METHODS: Transcriptional profiles of four S. aureus strains grown in broth supplemented or not with 2 mg/ml of a commercial cranberry preparation (Nutricran90) were compared using DNA arrays to reveal gene modulations serving as markers for biological activity. Ethanol extracted pressed cakes from fresh fruits also produced various fractions and their effects on marker genes were demonstrated by qPCR. Minimal inhibitory concentrations (MICs) of the most effective cranberry fraction (FC111) were determined against multiple S. aureus strains and drug interactions with -lactam antibiotics were also evaluated. Incorporation assays with [(3)H]-radiolabeled precursors were performed to evaluate the effect of FC111 on DNA, RNA, peptidoglycan (PG) and protein biosynthesis.
RESULTS: Treatment of S. aureus with Nutricran90 or FC111 revealed a transcriptional signature typical of PG-acting antibiotics (up-regulation of genes vraR/S, murZ, lytM, pbp2, sgtB, fmt). The effect of FC111 on PG was confirmed by the marked inhibition of incorporation of D-[(3)H]alanine. The combination of -lactams and FC111 in checkerboard assays revealed a synergistic activity against S. aureus including strain MRSA COL, which showed a 512-fold drop of amoxicillin MIC in the presence of FC111 at MIC/8. Finally, a therapeutic proof of concept was established in a mouse mastitis model of infection. S. aureus-infected mammary glands were treated with amoxicillin, FC111 or a combination of both; only the combination significantly reduced bacterial counts from infected glands (P<0.05) compared to the untreated mice.
CONCLUSIONS: The cranberry fraction FC111 affects PG synthesis of S. aureus and acts in synergy with -lactam antibiotics. Such a fraction easily obtained from poorly exploited press-cake residues, may find interesting applications in the agri-food sector and help reduce antibiotic usage in animal food production.
Abstract: The motility of bacteria plays a key role in their colonization of surfaces during infection. Derivatives of cranberry fruit have been shown to interfere with bacterial motility. Herein, we report on the incorporation of cranberry derived materials (CDMs) into silicone substrates with the aim of impairing bacterial pathogen motility and spreading on the substrate surface. The release of CDMs from the silicone substrates when soaking in an aqueous medium was quantified for a period of 24h. Next, we showed that CDMs released from two silicone substrates remain bioactive as they downregulate the expression of the flagellin gene of two key uropathogens - Escherichia coli CFT073 and Proteus mirabilis HI4320. Furthermore, we demonstrate that CDM-modified silicone inhibits the swarming motility of P. mirabilis, an aggressive swarmer. The bioactive, CDM-modified substrates can find broad applications in the medical device and food industries where the impairment of bacterial colonization of surfaces is of paramount importance.
Abstract: BACKGROUND: Periodontitis is a polymicrobial infectious disease. A novel potential chemical treatment modality may lie in bacterial anti-adhesive materials, such as cranberry juice fractions. The aim of this study is to explore the effect of high molecular weight cranberry constituent (non-dialyzable material [NDM]) on the virulence of a mixed infection with Porphyromonas gingivalis and Fusobacterium nucleatum in mice.
METHODS: In vitro, the anti-adhesive property of NDM was validated on epithelial cell culture, and inhibition of coaggregation was tested using a coaggregation assay. The in vivo effect was tested on the outcome of experimental periodontitis induced by a P. gingivalis and F. nucleatum mixed infection, and also on the local host response using the subcutaneous chamber model of infection. Phagocytosis was also tested on RAW macrophages by the use of fluorescent-labeled bacteria.
RESULTS: NDM was found to inhibit the adhesion of both species of bacteria onto epithelial cells and to inhibit coaggregation in a dose-dependent manner. NDM consumption by mice attenuated the severity of experimental periodontitis compared with a mixed infection without NDM treatment. In infected subcutaneous chambers, NDM alone reduced tumor necrosis factor-alpha (TNF-alpha) levels induced by the mixed infection. In vitro, NDM eliminated TNF-alpha expression by macrophages that were exposed to P. gingivalis and F. nucleatum, without impairing their viability. Furthermore, NDM increased the phagocytosis of P. gingivalis.
CONCLUSIONS: The results indicate that the use of NDM may hold potential protective and/or preventive modalities in periodontal disease. Underlying mechanisms for this trait may perhaps be the anti-adhesive properties of NDM or its potential effect on inflammation.
Abstract: The antimicrobial properties of the American cranberry were studied against Escherichia coli O157:H7, Listeria monocytogenes, and Lactobacillus rhamnosus to determine the effects on growth inhibition, membrane permeability, and injury. Cranberry powder was separated using a C-18 Sep-Pak cartridge into sugars plus organic acids (F1), monomeric phenolics (F2), and anthocyanins plus proanthocyanidins (F3). Fraction 3 was further separated into anthocyanins (F4) and proanthocyanidins (F5) using an LH-20 Sephadex column. Each fraction was diluted in the brain heart infusion (BHI) broth to determine the minimum inhibitory/bactericidal concentrations (MIC/MBC). L. monocytogenes was the most susceptible to cranberry fraction treatment with the lowest MIC/MBC for each treatment, followed by E. coli O157:H7 and L. rhamnosus. Membrane permeability and potential was studied using LIVE/DEAD viability assay and using Bis (1, 3-dibutylbarbituric acid) trimethine oxonol (DiBAC4), respectively. L. rhamnosus demonstrated the highest permeability followed by E. coli O157:H7, and L. monocytogenes. L. rhamnosus demonstrated the highest recovery followed by E. coli O157:H7, and L. monocytogenes. Each cranberry fraction demonstrated membrane hyperpolarization at their native pH, while F2, F3, and F5 demonstrated membrane depolarization at neutral pH. With this knowledge cranberry compounds may be used to prevent maladies and potentially substitute for synthetic preservatives and antibiotics.
Abstract: Cranberry A-type proanthocyanidins (PACs) have been recognized for their inhibitory activity against bacterial adhesion and biofilm-derived infections. However, the precise identification of the specific classes of degree-of-polymerization (DP) conferring PACs bioactivity remains a major challenge owing to the complex chemistry of these flavonoids. In this study, chemically characterized cranberries were used in a multistep separation and structure-determination technique to isolate A-type PAC oligomers of defined DP. The influences of PACs on the 3D architecture of biofilms and Streptococcus mutans-transcriptome responses within biofilms were investigated. Treatment regimens that simulated topical exposures experienced clinically (twice-daily, 60s each) were used over a saliva-coated hydroxyapatite biofilm model. Biofilm accumulation was impaired, while specific genes involved in the adhesion of bacteria, acid stress tolerance, and glycolysis were affected by the topical treatments (vs the vehicle-control). Genes (rmpC, mepA, sdcBB, and gbpC) associated with sucrose-dependent binding of bacteria were repressed by PACs. PACs of DP 4 and particularly DP 8 to 13 were the most effective in disrupting bacterial adhesion to glucan-coated apatitic surface (>85% inhibition vs vehicle control), and gene expression (eg rmpC). This study identified putative molecular targets of A-type cranberry PACs in S. mutans while demonstrating that PAC oligomers with a specific DP may be effective in disrupting the assembly of cariogenic biofilms.
Abstract: BACKGROUND: Recurrent urinary tract infections (UTIs) increase mortality and reduce graft survival after renal transplantation. Strategies to prevent recurrent UTIs include L-methionine, cranberry juice, and antibiotics. Data on the efficacy of cranberry and L-methionine, however, are controversial in the general population; there are few data in renal transplant recipients.
METHODS: We performed a retrospective analysis of 82 transplant recipients with recurrent UTIs, who underwent prophylaxis with cranberry juice (2 x 50 mL/d, n = 39, 47.6%), or L-methionine (3 x 500 mg/d, n = 25, 30.5%), or both modalities (n = 18, 21.9%). Thirty patients without prophylaxis served as controls. We analyzed symptoms, pyuria/nitrituria, and incidence of UTI events during 1 year before versus after initiation of prophylaxis.
RESULTS: Prophylaxis highly significantly decreased the annual UTI incidence by 58.3% (P < .001) in the study population with no change in the control group (P = .85); in addition, 53.7% of symptomatic patients reported relief of symptoms and pyuria/nitrituria disappeared in 42.4% of the dipstick-positive patients (P < .001 each). Cranberry reduced the annual number of UTI episodes by 63.9% from 3.6 +/- 1.4 to 1.3 +/- 1.3/year (P < .001) and L-methionine by 48.7% from 3.9 +/- 1.8 to 2.0 +/- 1.3/year (P < .001).
CONCLUSION: Cranberry juice and L-methionine successfully reduced the incidence of UTI after renal transplantation.
Abstract: Lactobacillus plantarum IFPL935 was incubated with individual monomeric flavan-3-ols and dimeric A- and B-type procyanidins to identify new metabolites and to determine the effect of compound structural features on bacterial growth and catabolism. Complex extracts rich in A-type proanthocyanidins and phenolic acids from cranberry were also tested. The results showed that L. plantarum IFPL935 exhibited higher resistance to nongalloylated monomeric flavan-3-ols, A-type dimeric procyanidins, and cranberry extract than to (−)-epicatechin-3-O-gallate and B-type dimeric procyanidins. Despite these findings, the strain was capable of rapidly degrading (−)-epicatechin-3-O-gallate, but not A- or B-type dimeric procyanidins. However, it
was able to produce large changes in the phenolic profile of the cranberry extract mainly due to the catabolism of
hydroxycinnamic and hydroxybenzoic acids. Of most relevance was the fact that L. plantarum IFPL935 cleaved the heterocyclic ring of monomeric flavan-3-ols, giving rise to 1-(3′,4′-dihydroxyphenyl)-3-(2″,4″,6″-trihydroxyphenyl)propan-2-ol, activity exhibited by only a few human intestinal bacteria.
Abstract: Purpose: Proanthocyanidins found in cranberry have been reported to have in vitro and in vivo antibacterial activity. We determined the effectiveness of cranberry juice for the prevention of urinary tract infections in children.
Materials and Methods: A total of 40 children were randomized to receive daily cranberry juice with high concentrations of proanthocyanidin vs cranberry
juice with no proanthocyanidin for a 1-year period. The study was powered to detect a 30% decrease in the rate of symptomatic urinary tract infection with type I and II errors of 0.05 and 0.2, respectively. Toilet trained children up to age 18 years were eligible if they had at least 2 culture
documented nonfebrile urinary tract infections in the calendar year before enrollment. Patients with anatomical abnormalities (except for primary vesicoureteral
reflux) were excluded from study. Subjects were followed for 12 months. The participants, clinicians, outcome assessor and statistician were all blinded to treatment allocation.
Results: Of the children 39 girls and 1 boy were recruited. Mean and median patient age was 9.5 and 7 years, respectively (range 5 to 18). There were 20 patients with comparable baseline characteristics randomized to each group. After 12 months of followup the average incidence of urinary tract infection in the treatment group was 0.4 per patient per year and 1.15 in the placebo group
(p 0.045), representing a 65% reduction in the risk of urinary tract infection.
Conclusions: Cranberry juice with high concentrations of proanthocyanidin appears to be effective in the prevention of pediatric nonfebrile urinary tract infections. Further studies are required to determine the cost-effectiveness of this approach.
Abstract: The effects of 13 food extracts and juices, including shellfish, fruits, and vegetables, on the binding ability of human norovirus (NoV) were examined, using P particles of human NoV GII.4 as a research surrogate. The enhancements (positive values) or reductions (negative values) of NoV P particle detection (changes in optical density at 450 nm) in the presence of different
food extracts and juices as compared with P particles diluted in phosphate-buffered saline were tested by saliva-binding, enzymelinked immunosorbent assay in triplicate. In the presence of different food extracts and juices at different concentrations, an increase or decrease of the receptor-binding ability of the NoV P particles was observed. Due to a higher specific binding and thus a higher
accumulation of the viral particles, oysters may be contaminated with human NoV more often than other shellfish species (mussel, hard clams, and razor clams). Cranberry and pomegranate juices were shown to reduce the specific binding ability of human NoV P particles. No such binding inhibition effects were observed for the other tested extracts of fresh produce (strawberry, blackberry,
blueberry, cherry tomato, spinach, romaine lettuce) or, notably, for raspberry, which has been associated with human NoV outbreaks.
Abstract: The experiment consisted in assessing the effectiveness of a commercial product based on cranberry extracts (pHDReg.-Biomin LTDA) in the treatment of urinary tract infections (UTI) in sows. Were used 42 sows, with gestational ages ranging between 50 and 70 days, either suffering from UTI or not. Healthy animals were differentiated from affected animals by urinalysis and urine culture. The experiment was composed of sows with UTI that received the cranberry extract product in the diet for a period of 14 days; sows negative for UTI (negative controls) and sows positive for UTI (positive controls). The former two groups did not receive the cranberry extract product in the diet. Urine samples were collected on days zero, seven and 14 after initiation of treatment. Complete urinalysis of these samples, urine specific gravity, pH, bacterial count and bacterial isolation were performed. E. coli was the most frequent isolated agent (90.62%). The results showed that the commercial product made with cranberry extract was effective in promoting a reduction of urinary pH, but did not interfere in any other parameters observed.
Abstract: Background: Cranberry (Vaccinium macrocarpon) proanthocyanidins can interfere with adhesion of bacteria to uroepithelial cells, potentially preventing lower urinary tract infections (LUTIs). Because LUTIs are a common side effect of external beam radiotherapy (EBRT) for prostate cancer, we evaluated the clinical efficacy of enteric-coated tablets containing highly standardized V. msacrocarpon (ecVM) in this condition.
Methods: A total of 370 consecutive patients were entered into this study. All patients received intensity-modulated radiotherapy for prostate cancer; 184 patients were also treated with ecVM while 186 served as controls. Cranberry extract therapy started on the simulation day, at which time a bladder catheterization was performed. During EBRT (over 6–7 weeks), all patients underwent weekly examination for urinary tract symptoms, including regular urine cultures during the treatment period.
Results: Compliance was excellent, with no adverse effects or allergic reactions being observed, apart from gastric pain in two patients. In the cranberry cohort (n = 184), 16 LUTIs (8.7%) were observed, while in the control group (n = 186) 45 LUTIs (24.2%) were recorded. This difference was statistically significant. Furthermore, lower rates of nocturia, urgency, micturition frequency, and dysuria were observed in the group that received cranberry extract.
Conclusion: Cranberry extracts have been reported to reduce the incidence of LUTIs significantly in women and children. Our data extend these results to patients with prostate cancer undergoing irradiation to the pelvis, who had a significant reduction in LUTIs compared with controls. These results were accompanied by a statistically significant reduction in urinary tract symptoms (dysuria, nocturia, urinary frequency, urgency), suggesting a generally protective effect of cranberry extract on the bladder mucosa.
Abstract: Surface-associated swarming motility is implicated in enhanced bacterial spreading and virulence, hence it follows
that anti-swarming effectors could have clinical benefits. When investigating potential applications of anti-swarming
materials it is important to consider whether the lack of swarming corresponds with an enhanced sessile biofilm
lifestyle and resistance to antibiotics. In this study, well-defined tannins present in multiple plant materials (tannic
acid (TA) and epigallocathecin gallate (EGCG)) and undefined cranberry powder (CP) were found to block swarming motility and enhance biofilm formation and resistance to tobramycin in Pseudomonas aeruginosa. In contrast, gallic acid (GA) did not completely block swarming motility and did not affect biofilm formation or tobramycin resistance. These data support the theory that nutritional conditions can elicit an inverse relationship between swarming motility and biofilm formation capacities. Although anti-swarmers exhibit the potential to yield clinical benefits, it is important to be aware of possible implications regarding biofilm formation and antibiotic resistance.
Abstract: Natural chemicals have been reported to have antibacterial effects against a variety of bacteria. The present study evaluated the antibacterial effects of commercially available grape-seed extract (GSE), pomegranate polyphenols (PP), and lab-prepared cranberry proanthocyanidins (C-PAC) against two strains of methicillin-resistant Staphylococcus aureus (MRSA). GSE, PP, and C-PAC at concentrations of 2 mg/mL, 10 mg/mL, or controls were mixed with equal volumes of overnight cultures of MRSA at ~6 log10 colony-forming units (CFU)/mL and incubated for 0, 1, 2, 8, and 24 h at 37 degrees C. Treatments were neutralized/stopped using tryptic soy broth containing 3% beef extract. Serial dilutions of the treated MRSA strains and controls were spread-plated on trypticase soy agar and incubated for 24-48 h at 37 degrees C and colonies were counted. Among the three tested agents, GSE at 1 and 5 mg/mL was found to be most effective against MRSA, resulting in a 2.9-4.0 log10 CFU/mL reduction of both strains after 2 h at 37 degrees C. PP at 1 and 5 mg/mL was found to cause 1.1-2.3 log10 CFU/mL reduction, while C-PAC at 1 mg/mL caused <1 log10 CFU/mL reduction of the two MRSA strains after 2 h at 37 degrees C. All three extracts at the tested concentrations decreased the two MRSA strains to undetectable levels within 24 h, with the exception of 1 mg/mL PP for strain 33591. Scanning electron microscopy of MRSA after 2 h of treatment showed that GSE and PP caused bacterial cell wall alteration, with negligible effect observed by C-PAC treatment. However, the in vivo activity and clinical safety applications of GSE, PP, and C-PAC need to be evaluated before suggestion for use as a treatment/control measure.
Abstract: The 4-(dimethylamino)cinnamaldehyde (DMAC) assay is currently used to quantify proanthocyanidin (PAC) content in cranberry products. However, this method suffers from issues of accuracy and precision in the analysis and comparison of PAC levels across a broad range of cranberry products. Current use of procyanidin A2 as a standard leads to an underestimation of PACs content in certain cranberry products, especially those containing higher molecular weight PACs. To begin to address the issue of accuracy, a method for the production of a cranberry PAC standard, derived from an extraction of cranberry (c-PAC) press cake, was developed and evaluated. Use of the c-PAC standard to quantify PAC content in cranberry samples resulted in values that were 2.2 times higher than those determined by procyanidin A2. Increased accuracy is critical for estimating PAC content in relationship to research on authenticity, efficacy, and bioactivity, especially in designing clinical trials for determination of putative health benefits.
Abstract: "Aims:  Periodontitis is an inflammatory disease of polymicrobial origin that affects the tooth-supporting tissues. With the spread of antibiotic resistance among pathogenic bacteria, alternative strategies are required to better control infectious diseases such as periodontitis. The aim of our study was to investigate whether two natural compounds, A-type cranberry proanthocyanidins (AC-PACs) and licochalcone A, act in synergy against Porphyromonas gingivalis and the host inflammatory response of a macrophage model.
Methods and Results:  Using a checkerboard microtitre test, AC-PACs and licochalcone A were found to act in synergy to inhibit P. gingivalis growth and biofilm formation. Fluorescein isothiocyanate-labelled P. gingivalis adhesion to oral epithelial cells was also inhibited by a combination of the two natural compounds in a synergistic manner. Fluorometric assays showed that although AC-PACs and licochalcone A reduced both MMP-9 and P. gingivalis collagenase activities, no synergy was obtained with a combination of the compounds. Lastly, AC-PACs and licochalcone A also acted in synergy to reduce the lipopolysaccharide (LPS)-induced secretion of the pro-inflammatory mediators IL-1β, TNF-α, IL-6 and IL-8 in a macrophage model.
Conclusions:  A-type cranberry proanthocyanidins and licochalcone A, natural compounds from cranberry and licorice, respectively, act in synergy on both P. gingivalis and the host immune response, the two principal etiological factors of periodontitis.
Significance and Impact of the Study:  The combined use of AC-PACs and licochalcone A may be a potential novel therapeutic strategy for the treatment and prevention of periodontal disease."
Abstract: Objectives: The present study forms part of the ISRCTN16968287 clinical assay. The objective of this study was to determine the effectiveness of cranberry syrup in the prophylaxis of recurrent urinary tract infection (UTI).
Design: Phase III randomized clinical trial. Setting: The study was conducted at the San Cecilio Clinical Hospital (Granada, Spain). Participants: A total of 192 patients were recruited. The subjects were aged between 1 month and 13 years. Criteria for inclusion were a background of ecurrent UTI (more than two episodes of infection in the last 6 months), associated or otherwise with vesicoureteral reflux of any degree, or renal pelvic dilatation associated with UTI. Criteria for exclusion from recruitment to the study included the co-existence of UTI with other infectious diseases or with metabolic diseases, chronic renal insufficiency, and the presence of allergy or intolerance to any of the components of cranberry syrup or trimethoprim.
Primary outcome measures: The primary objective was to determine the risk of UTI associated with each intervention.
Results: Of the 198 patients initially eligible, 192 were finally included in the study to receive either cranberry syrup or trimethoprim. UTI was observed in 47 patients, 17 of whom were males and 30 females. We recruited 95 patients diagnosed with recurrent UTI on entry; during
follow-up, 26 patients had a UTI (27.4%, 95% CI: 18.4%–36.3%). Six patients (6.3%) were male and 20 (21.1%) were female. Eighteen patients (18.9% of the total, 95% CI: 11%–26.3%) receiving trimethoprim had a UTI and eight patients (8.4% of the total, 95% CI: 2.8%–13.9%) were given cranberry. Sixty-six percent of the episodes of UTI recurrence were caused by Escherichia coli, with no significant differences being found between the two
treatment branches. No differences were observed between the two treatment branches in the rate of resistance to antibiotics.Conclusion: Our study confirms that cranberry syrup is a safe treatment for the pediatric population. Cranberry prophylaxis has noninferiority with respect to trimethoprim in recurrent UTI.
Abstract: BACKGROUND Urinary tract infection (UTI) is one of the most commonly acquired bacterial infections. Cranberry-containing products have long been used as a folk remedy to prevent UTIs. The aims of this study were to evaluate cranberry-containing products for the prevention of UTI and to examine the factors influencing their effectiveness. METHODS MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were systemically searched 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. RESULTS Thirteen trials, including 1616 subjects, were identified for qualitative synthesis from 414 potentially relevant references; 10 of these trials, including a total of 1494 subjects, were further analyzed in quantitative synthesis. The random-effects pooled risk ratio (RR) for cranberry users vs nonusers was 0.62 (95% CI, 0.49-0.80), with a moderate degree of heterogeneity (I2 = 43%) after the exclusion of 1 outlier study. On subgroup analysis, cranberry-containing products seemed to be more effective in several subgroups, including women with recurrent UTIs (RR, 0.53; 95% CI, 0.33-0.83) (I2 = 0%), female populations (RR, 0.49; 95% CI, 0.34-0.73) (I2 = 34%), children (RR, 0.33; 95% CI, 0.16-0.69) (I2 = 0%), cranberry juice drinkers (RR, 0.47; 95% CI, 0.30-0.72) (I2 = 2%), and subjects using cranberry-containing products more than twice daily (RR, 0.58; 95% CI, 0.40-0.84) (I2 = 18%). CONCLUSIONS Our findings indicate that cranberry-containing products are associated with protective effect against UTIs. However, this result should be interpreted in the context of substantial heterogeneity across trials.
Abstract: In a randomized, double-blind, placebo-controlled clinical cross-over study with 18 subjects of both sexes (aged 21-52 years), the effect of cranberry (Vaccinium macrocarpon) and pumpkin seed extract combination (Cystorenal Cranberry plus) on the urinary tract through inhibition of Escherichia coli adherence to urothelial cells was examined. With the ingestion of Cystorenal Cranberry plus, the bacterial adherence was decreased by 33.4% compared to the placebo. The recommended amount of the preparation is sufficient to protect the healthy bladder. There was no adverse effects observed.
Abstract: Biofilm producing bacteria such as Staphylococcus species and Escherichia coli are the most common cause of catheter related urinary tract infections (UTIs). The American cranberry (Vaccinium macrocarpon) is utilized widely as a prophylaxis for UTIs due to its prevention of microbial adhesion. Cranberry contains proanthocyanidins (PACs), which have been implicated as active constituents responsible for its bacterial antiadhesive properties. Despite overwhelming data supporting cranberry's beneficial effects against human pathogenic bacteria, there is limited information regarding its effects on biofilm formation. This study evaluated the effects of three proprietary PAC-standardized cranberry extracts on the inhibition of bacterial growth and biofilm production against a panel of clinically relevant pathogens: Staphylococcus epidermidis, Staphylococcus aureus, clinical methicillin-resistant S. aureus (MRSA), Staphylococcus saprophyticus and Escherichia coli. The extracts inhibited the growth of the Gram-positive bacteria (Staphylococcus spp.) but not the Gram-negative species (E. coli) with minimum inhibitory concentrations in the range 0.02–5 mg/mL. The extracts also inhibited biofilm production by the Gram-positive bacteria but did not eradicate their established biofilm. These results suggest that cranberry may have beneficial effects against the growth and biofilm producing capability of Gram-positive bacteria pathogens.
Abstract: Cranberry juice contains high molecular weight non-dialyzable material (NDM) which was found to inhibit hemagglutination induced by the influenza virus (IV) as well as to neutralize the cytotoxicity of IV in cell cultures. Because influenza virus surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) are involved in viral replication and in the infectious process, we sought in the present study to examine the effect of NDM on neuraminidases which are the target of most anti-influenza drugs today. NDM inhibited the NA enzymatic activity of influenza A and B strains as well as that of Streptococcus pneumoniae. This finding is of importance considering the emergence of influenza isolates resistant to antiviral drugs, reaching 90 % in some places. The anti-NA activity of NDM, evaluated by the MUNANA method and expressed as the concentration required for 50 % inhibition (IC50), was most potent against N1 (IC50, 192 microg/mL), less active against BN and N2 (IC50, 509 microg/mL and 1128 microg/mL, respectively), and moderately active against Streptococcus pneumoniae NA (IC50, 594 microg/mL). The in vitro findings of the present study suggest that cranberry constituents may have a therapeutic potential against both A and B influenza virus infections and might also interfere with the development of secondary bacterial complications
Abstract: The impact of cranberry juice was investigated with respect to the initial adhesion of three isogenic strains of the bacterium Burkholderia cepacia with different extracellular polymeric substance (EPS) producing capacities, viz. a wild-type cepacian EPS producer PC184 and its mutant strains PC184rml with reduced EPS production and PC184bceK with a deficiency in EPS production. Adhesion experiments conducted in a parallel-plate flow chamber demonstrated that, in the absence of cranberry juice, strain PC184 had a significantly higher adhesive capacity compared to the mutant strains. In the presence of cranberry juice, the adhesive capacity of the EPS-producing strain PC184 was largely reduced, while cranberry juice had little impact on the adhesion behavior of either mutant strain. Thermodynamic modeling supported the results from adhesion experiments. Surface force apparatus (SFA) and scanning electron microscope (SEM) studies demonstrated a strong association between cranberry juice components and bacterial EPS. It was concluded that cranberry juice components could impact bacterial initial adhesion by adhering to the EPS and impairing the adhesive capacity of the cells, which provides an insight into the development of novel treatment strategies to block the biofilm formation associated with bacterial infection.
Abstract: Cranberry products are a nonantimicrobial
method for prevention of urinary tract infection
(UTI). Cranberry proanthocyanidin (PAC), a type of condensed tannin, is the active ingredient in cranberry that
inhibits adherence of P-fimbriated Escherichia coli to
uroepithelial cells. Previous cranberry studies for UTI
prevention yielded conflicting results, probably because
of variability of PAC dose and clinical populations studied. In a clinical trial of 300 mL of cranberry juice beverage daily (36 mg PAC), older women (mean age 78.5) had 58% lower odds of having bacteriuria and pyuria than controls, but nursing home residents have difficulty ingesting the volume of juice necessary to prevent bacteriuria. Cranberry capsules are feasible to administer to nursing home residents, but their efficacy has not been demonstrated. In vitro, 36–108 mg of PAC is efficacious at inhibiting bacterial adherence to uroepithelial cells, but the most efficacious dose for older nursing home residents has not been identified. The goal of this study was to identify the optimal dose of cranberry capsules that reduced the incidence of bacteriuria plus pyuria over 1 month.
Abstract: Objectives. The aim of this randomized controlled prospective study is to evaluate the efficacy of cranberry capsules for prevention of UTI in children with neurogenic bladder caused by myelomeningocele. Patients and Methods. To be eligible for this study, patients had to be diagnosed as neurogenic bladder caused by myelomeningocele, evaluated urodynamically, followed up with clean intermittent catheterization and anticholinergic drugs. Intervention. Six months of treatment with placebo; after a week of wash-out period treatment of cranberry extract tablets (1 capsule/day) for an additional 6 months. Randomization was performed sequentially. Patients and care givers were blinded to drug assignment. Main outcome measure was infection rate. Group comparisons were performed with Wilcoxon test. Results. The study population included 20 (F/M: 13/7) patients with neurogenic bladder with the mean age of 7.25 ± 3.49 (4, 18) years. The median UTI rate was 0.5/year during placebo usage whereas 0/year during cranberry capsule usage. Decrease in infection rate was significant with cranberry capsule usage (P = 0.012). Decrease in the percentage of the pyuria was also recorded as significant (P = 0.000). Any adverse events or side effects were not recorded. Conclusion. We concluded that cranberry capsules could be an encouraging option for the prevention of recurrent UTI in children with neurogenic bladder caused by myelomeningocele.
Radical pelvic radiotherapy is one of the main treatment modalities for cancers of the bladder and cervix. The side-effects of pelvic radiotherapy include urinary symptoms, such as urinary frequency and cystitis. The therapeutic effects of cranberry juice in the prevention and treatment of urinary tract infections in general are well documented. The purpose of this study was to evaluate the effectiveness of cranberry juice on the incidence of urinary tract infections and urinary symptoms in patients undergoing pelvic radiotherapy for cancer of the bladder or cervix.
MATERIALS AND METHODS:
The study was a placebo-controlled, double-blind design. Participants were randomised to receive cranberry juice, twice a day (morning and night) for the duration of their radiotherapy treatment and for 2 weeks after treatment (6 weeks in total) or a placebo beverage, for the same duration.
The incidence of increased urinary symptoms or urinary tract infections was 82.5% on cranberry and 89.3% on placebo (P=0.240, adjusted odds ratio [cranberry/placebo] 0.48, 95% confidence interval 0.14-1.63).
The power of the study to detect differences was limited by the below target sample size and poor compliance. Further research is recommended, taking cognisance of the factors contributing to the limitations of this study.
Abstract: The antimicrobial effect of thirty HPLC fractions of different polarity obtained from two cranberry juices and three extracts (anthocyanins, water-soluble and apolar phenolic compounds) isolated from frozen cranberries and pomace was investigated against seven bacterial strains Enterococcus faecium resistant to vancomycin (ERV), Escherichia coli O157:H7 EDL 933, Escherichia coli ATCC 25922, Listeria monocytogenes HPB 2812, Pseudomonas aeruginosa ATCC 15442; Salmonella Typhimurium SL1344 and Staphylococcus aureus ATCC 29213) The minimum inhibitory concentration (MIC) and the maximal tolerated concentration (MTC) of each fraction were determined for each pathogen using a 96-well microtiter plate method. The results, reported in mg phenol/mL, indicated that all the bacterial strains, both Gram-positive and Gram-negative, were selectively inhibited by the cranberry phenolic compounds. All pathogens were very sensitive to at least seven fractions with MTCs below 2 mg phenol/mL and five fractions with MICs below 10 mg phenol/mL. In addition, four fractions rich in apolar phenolic compounds were very efficient against all bacteria with MICs below 10 mg phenol/mL, and twenty five fractions completely inhibited microbial growth with MICs below100 mg phenol/well. L. monocytogenes exhibited the highest sensitivity with twelve very active fractions (MTCs and MICs below 1 and
10 mg phenol/mL, respectively) while E. coli O157H7 was the least sensitive to twenty seven fractions (with the highest MICs). Also, it appears that the technological process to manufacture cranberry juice can reduce the antimicrobial activity of phenolic fractions.
Abstract: Cranberry-lingonberry juice (CLJ) was effective in preventing urinary tract infections (UTIs) in our earlier randomized clinical trial. We aimed to test whether consumption of CLJ at a similar dose to earlier reduces the biofilm formation and virulence of uropathogenic Escherichia coli in urine. Twenty healthy women drank 100 ml of CLJ daily for two weeks. Urine samples were obtained 2–4 hours after the last dose. Control samples were taken after a one-week period without berry consumption. Biofilm formation of 20 E. coli strains was measured at 72 hours by the polystyrene microtitre plate method. Quantitative real-time PCR analyses were performed for selected genes. Four of the 20 clinical strains produced more biofilm in urine after CLJ consumption (P < 0.05) and one produced less. Expression levels of the pga, cpxA, fimA and papF genes did not differ between bacteria grown in control urine and urine obtained after CLJ consumption, except for pga gene expression, which was reduced in one strain after CLJ (P = 0.04). It appears that the effect of CLJ in preventing UTIs is not explained by mechanisms that reduce biofilm formation or the expression of selected virulence genes of Escherichia coli in urine.
Abstract: Cranberry ( Vaccinium macrocarpon ) products have been widely recommended in traditional American medicine for the treatment of urinary tract infection (UTI). A total of 19 different commercial cranberry products from American and European markets have been analyzed by different global phenolic methods and by UPLC-DAD-ESI-TQ MS. In addition, in vitro antioxidant capacity and uropathogenic bacterial antiadhesion activity tests have been performed. Results revealed that products found in the market widely differed in their phenolic content and distribution, including products completely devoid of flavan-3-ols to highly purified ones, either in A-type proanthocyanidins (PACs) or in anthocyanins. The product presentation form and polyphenolic profile widely affected the antiadhesion activity, ranging from a negative (nulel) effect to a MIC = 0.5 mg/mL for cranberry powders and a MIC=112 mg/mL for gel capsule samples. Only 4 of 19 products would provide the recommended dose of intake of 36 mg total PACs/day. Of most importance was the fact that this dose would actually provide as low as 0.00 and up to 205 μg/g of procyanidin A2, indicating the lack of product standardization and incongruence between global and individual compound analysis.
Abstract: ABSTRACT: BACKGROUND: Oral candidiasis is a common fungal disease mainly caused by Candida albicans. The aim of this study was to investigate the effects of A-type cranberry proanthocyanidins (AC-PACs) on pathogenic properties of C. albicans as well as on the inflammatory response of oral epithelial cells induced by this oral pathogen. METHODS: Microplate dilution assays were performed to determine the effect of AC-PACs on C. albicans growth as well as biofilm formation stained with crystal violet. Adhesion of FITC-labeled C. albicans to oral epithelial cells and to acrylic resin disks was monitored by fluorometry. The effects of AC-PACs on C. albicans-induced cytokine secretion, nuclear factor-kappa B (NF-kappaB) p65 activation and kinase phosphorylation in oral
epithelial cells were determined by immunological assays. RESULTS: Although AC-PACs did not affect growth of C. albicans, it prevented biofilm formation and reduced adherence of C. albicans to oral epithelial cells and saliva-coated acrylic resin discs. In addition, AC-PACs significantly decreased the secretion of IL-8 and IL-6 by oral epithelial cells stimulated with C. albicans. This
anti-inflammatory effect was associated with reduced activation of NF-kappaB p65 and phosphorylation of specific signal intracellular kinases. CONCLUSION: AC-PACs by affecting the adherence properties of C. albicans and attenuating the inflammatory response induced by this pathogen represent potential novel therapeutic agents for the prevention/treatment of oral candidiasis.
Abstract: Proanthocyanidin is commonly used for inhibiting urinary tract infection (UTI) of sensitive strains of Escherichia coli. The aim of this study was to investigate the effect of proanthocyanidin on adherence of uropathogenic multi-drug resistant E. coli to uroepithelial cells, which has not yet been investigated so far. Extracts of the purified proanthocyanidin were prepared from dried cranberry juice. Purity and structural assignment of proanthocyanidin was assessed using high performance liquid chromatography and (13)C nuclear magnetic resonance spectroscopy, respectively. Subsequently, its affect on multi-drug resistant bacteria as well as quantification of anti-adherence bioactivity on human vaginal and bladder epithelial cells was appraised. Inhibition of adherence to an extent of about 70% with multi-drug resistant E. coli strains was observed on uroepithelial cell. The anti-adherence bioactivity of the proanthocyanidin was detected at concentrations of 10-50 µg/ml with significant bacteriuria. Probable proanthocyanidin through A-type linkages either combines to P-fimbriae of bacterial cells or modifies the structural entity of P-fimbriae and inhibits bacterial adherence to uroepithelial cells. The proanthocyanidin exhibited anti-adherence property with multi-drug resistant strains of uropathogenic P-fimbriated E. coli with in vitro study. Hence proanthocyanidin may be considered as an inhibitory agent for multi-drug resistant strains of E. coli adherence to uroepithelial cells.
Abstract: Previous studies demonstrated that a cranberry high-molecular-mass, nondialyzable material (NDM) can inhibit adhesion of numerous species of bacteria and prevents bacterial coaggregation of bacterial pairs. Bacterial coaggregation leads to plaque formation leading to biofilm development on surfaces of oral cavity. In the present study, we evaluated the effect of low concentrations of NDM on Streptococcus gordonii metabolic activity and biofilm formation on restorative dental surfaces. We found that the NDM selectively inhibited metabolic activity of S. gordonii, without affecting bacterial viability. Inhibiting the metabolic activity of bacteria in biofilm may benefit the health of the oral cavity.
To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice daily.
PATIENTS AND METHODS:
Premenopausal women with a history of recent UTI were enrolled from November 16, 2005, through December 31, 2008, at 2 centers and randomized to 1 of 3 arms: 4 oz of cranberry juice daily, 8 oz of cranberry juice daily, or placebo juice. Time to UTI (symptoms plus pyuria) was the main outcome. Asymptomatic bacteriuria, adherence, and adverse effects were assessed at monthly visits.
A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days. The cumulative rate of UTI was 0.29 in the cranberry juice group and 0.37 in the placebo group (P=.82). The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 0.68 (95% confidence interval, 0.33-1.39; P=.29). The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (43.5%) in the cranberry juice group and 8 of 10 (80.0%) in the placebo group (P=.07). The mean dose adherence was 91.8% and 90.3% in the cranberry juice group vs the placebo group. Minor adverse effects were reported by 24.2% of those in the cranberry juice group and 12.5% in the placebo group (P=.07).
Cranberry juice did not significantly reduce UTI risk compared with placebo. The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger, well-powered studies of women with recurrent UTI. The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity.
clinicaltrials.gov Identifier: NCT00128128.
Abstract: Consumption of cranberries is known to exert positive health effects, especially against urinary tract infections. For this reason, presumably, they are widely used in folk medicine. Different aspects of cranberry phenolics activity were studied in individual papers but complex study in this matter is missing. The aim of the present study is to provide complex data concerning various aspects of cranberry extract activity. We studied the effects of subinhibitory concentrations of commercially available extract (Żuravit S·O·S(®)) against two Escherichia coli strains isolated from urine of patients with pyelonephritis. Additionally the main extract anthocyanins were characterized. The activity of extract against lipid peroxidation and its radical scavenging ability were also assessed. Żuravit S·O·S(®) decreased the hydrophobicity of one of the studied E. coli strains, reduced swimming motility and adhesion to epithelial cells of both studied strains, it also limited the ability of bacteria to form biofilm. Expression of curli was not affected by cranberry extract, the assessment of P fimbriae expression was not reliable due to extract-induced agglutination of erythrocytes. Cranberry extract caused filamentation in both studied E. coli strains. It also showed pronounced antioxidant and radical scavenging properties. The properties of the studied cranberry extract show that it could be effectively used in prevention and/or elimination of urinary tract infections, specially the recurrent ones.
Abstract: The antimicrobial effects of the American cranberry (Vaccinium macrocarpon) on a major food-borne pathogen, Staphylococcus aureus, were investigated using commercially obtained Lakewood® organic cranberry juice and Ocean Spray® cranberry juice cocktail and four other berry fruit extracts (acai berry, strawberry, raspberry, and blueberry). The results showed that cranberry is a potent antimicrobial against S. aureus and the most potent among the berries studied. The order of percentage inhibition of bacterial growth at the same concentration of phenolic materials as gallic acid equivalents was Lakewood cranberry juice > Ocean Spray cranberry juice ≫ blueberry > acai berry ≫ raspberry ≫ strawberry. The antimicrobial effect was not due to the acidity of the berries as NaOH-neutralized samples were almost as effective in terms of percentage inhibition of viable cell growth. Solid-phase extraction of cranberry juice using C18 solid phase showed that the antimicrobial effects reside exclusively with the C18-bound materials.
Abstract: Urinary tract infections (UTIs) represent a recurrent health problem especially for women. More than 50% of women will suffer from a UTI at least once in their lifetime. Cranberries have long been used for their beneficial effects in preventing symptomatic UTIs in several published studies. However, cranberry products used in these clinical studies do not indicate the amount of active ingredients delivered that help to prevent UTIs. Therefore, a dose-dependent study was designed to understand the impact and safety profile of a standardized cranberry product (Proanthocyanidins Standardized Whole Cranberry Powder,PS-WCP) on reducing the recurrences of symptomatic UTI in culture-positive subjects. A 90- day randomized clinical trial including an untreated control group with a total of 60 female subjects between 18-40 years of age was conducted. Study subjects were randomly selected and assigned to three groups including an untreated control group (n=16), a low dose (500 mg daily, n=21) and a high dose (1000 mg daily, n=23) treatment group. The safety of PSWCP was assessed by evaluation of biochemical and hematological parameters on days 10, 30, 60 and 90 during the study, comparing the values with those at the baseline. Occurrence of UTI at baseline and during the follow-up period was characterized by the presence of symptoms and Escherichia coli in the culture of urine samples. The statistical analysis used was ANOVA. At the end of the 90-day treatment period, no significant changes were observed in the hematological and serum biochemical parameters. At the end of the study, change in the presence of E. coli in the untreated control group was not significant (p=0.7234), whereas, there was significant reduction (p<0.05) in the subjects positive for E. coli in both the high dose and low dose treatment groups, compared to baseline evaluation. Symptomatic relief was also reported in the low and high dose treatment groups, while none was reported by subjects in the untreated control group. In conclusion, PS-WCP was effective in safely reducing the number of E. coli positive subjects at both the 500 mg and 1000 mg dose levels and in ameliorating the symptoms of UTI in these subjects. Therefore, a daily dose of 500 mg or 1000 mg of PS-WCP may be considered as an adjunct to antibiotic prophylactic therapy against recurrent UTIs.
Abstract: Absorption and excretion of twenty cranberry-derived phenolics were studied following the consumption of cranberry juice, sauces, and fruits by healthy human volunteers. Plasma and urine samples were collected and analysed by gas chromatography–mass spectrometry (GC–MS). A high performance liquid chromatography (HPLC) method was employed for analysing urinary creatinine, which was used as a normalisation agent. Significant increases in the sum of plasma phenolics were observed with different concentration peaks (between 0.5 and 2 h) for individual subjects. Some of the phenolics, such as trans-cinnamic, vanillic, p-coumaric acids, and catechin showed second plasma concentration peaks. All of cranberry-derived phenolics increased significantly in urine samples after the intake of each cranberry product. The high molecular weight quercetin and myricetin, which were abundant in cranberry foodstuffs, were not found in either plasma or urine samples. This study provided the fundamental information for understanding the absorption and excretion of phenolics in the human gastrointestinal system after dietary intake of cranberry products.
Abstract: Background. Cranberry juice prevents recurrences of urinary tract infections (UTIs) in adult women. The objective of this study was to evaluate whether cranberry juice is effective in preventing UTI recurrences in children.
Methods. A double-blind randomized placebo-controlled trial was performed in 7 hospitals in Finland. A total of 263 children treated for UTI were randomized to receive either cranberry juice (n = 129) or placebo (n = 134) for 6 months. Eight children were omitted because of protocol violations, leaving 255 children for the final analyses. The children were monitored for 1 year, and their recurrent
UTIs were recorded. Results. Twenty children (16%) in the cranberry group and 28 (22%) in the placebo group had at least 1 recurrent UTI (difference, -6%; 95% confidence interval [CI], -16 to 4%; P = .21). There were no differences in timing between these first recurrences (P = .32). Episodes of UTI totaled 27 and 47 in the cranberry and placebo groups, respectively, and the UTI incidence density per person-year at risk was 0.16 episodes lower in the cranberry group (95% CI, -.31 to -.01; P = .035). The children in the cranberry group had significantly fewer days on antimicrobials (-6 days per patient-year; 95% CI, -7 to -5; P < .001). Conclusions. The intervention did not significantly reduce the number of children who experienced a recurrence of UTI, but it was effective in
reducing the actual number of recurrences and related antimicrobial use.
Abstract: Cranberry ( Vaccinium macrocarpon ) is known to have a beneficial effect on several aspects of human health. Proanthocyanidins (PACs), the most abundant flavonoids extracted from red cranberry fruits, have been reported to possess antimicrobial, antiadhesion, antioxidant, and anti-inflammatory properties. Recent in vitro studies have shown that cranberry PACs may be potential therapeutic agents for the prevention and management of periodontitis, an inflammatory disease of bacterial origin affecting tooth-supporting tissues. After presenting an overview of cranberry phytochemicals and their potential for human health benefits, this review will focus on the effects of cranberry PACs on connective tissue breakdown and alveolar bone destruction, as well as their potential for controlling periodontal diseases. Possible mechanisms of action of cranberry PACs include the inhibition of (i) bacterial and host-derived proteolytic enzymes, (ii) host inflammatory response, and (iii) osteoclast differentiation and activity. Given that cranberry PACs have shown interesting properties in in vitro studies, clinical trials are warranted to better evaluate the potential of these molecules for controlling periodontal diseases.
Abstract: ABSTRACT Cranberry extract has been reported as a therapeutic agent, mainly in urinary tract infections due to its antiadhesive capacity. In order to compare the effects of proanthocyanidin (procyanidin) (PAC)-standardized cranberry extracts and commercial PAC A2, we first investigated the presence of genes encoding known adhesins on 13 strains of uropathogenic strains coming from patients with cystisis. After this characterization, the anti-adhesive effects of PAC A2 were assayed on selected uropathogenic Escherichia coli strains before testing cranberry extracts. Before checking inhibitory effect on bacterial adhesion to cells, we showed that neither PAC A2 or three cranberry extracts (A, B, and C) specifically inhibited the growth and did not supply any potential nutrient to E. coli strains, including the unrelated control strain. PAC A2 exhibited an inhibitory effect on the adhesion of two selected uropathogenic strains of E. coli. This work also showed that a preliminary exposure of bacteria to PAC A2 significantly reduced the adhesion. This phenomenon has been also observed with a lesser impact when uroepithelial cells were pretreated with PAC A2. Moreover, the assays were more robust when bacteria were in fast growing conditions (exponential phase): the adhesion to uroepithelial cells was greater. Significant reduction of adhesion to urepithelial cells was observed: around 80% of inhibition of adhesion with the cranberry extracts at equivalent PAC concentration of 50 µg/mL. The effects of the different assayed extracts were not obviously different except for extract B, which inhibited approximately 55% of adhesion at an equivalent PAC concentration of 5 µg/mL
Abstract: Cranberry juice cocktail (CJC) has been shown to inhibit the formation of biofilm by uropathogenic Escherichia coli. In order to investigate whether the anti-adhesive components could reach the urinary tract after oral consumption of CJC, a volunteer was given 16 oz of either water or CJC. Urine samples were collected at 0, 2, 4, 6, and 8 hours after consumption of a single dose. The ability of compounds in the urine to influence bacterial adhesion was tested for six clinical uropathogenic E. coli strains, including four P-fimbriated strains (B37, CFT073, BF1023, and J96) and two strains not expressing P-fimbriae but exhibiting mannose-resistant hemagglutination (B73 and B78). A non-fimbriated strain, HB101, was used as a control. Atomic force microscopy (AFM) was used to measure the adhesion force between a silicon nitride probe and bacteria treated with urine samples. Within 2 hours after CJC consumption, bacteria of the clinical strains treated with the corresponding urine sample demonstrated lower adhesion forces than those treated with urine collected before CJC consumption. The adhesion forces continued decreasing with time after CJC consumption over the 8-hour measurement period. The adhesion forces of bacteria after exposure to urine collected following water consumption did not change. HB101 showed low adhesion forces following both water and CJC consumption, and these did not change over time. The AFM adhesion force measurements were consistent with the results of a hemagglutination assay, confirming that oral consumption of CJC could act against adhesion of uropathogenic E. coli.
Abstract: Cranberry ( Vaccinium macrocarpon ) has been shown in clinical studies to reduce infections caused by Escherichia coli and other bacteria, and proanthocyanidins are believed to play a role. The ability of cranberry to inhibit the growth of opportunistic human fungal pathogens that cause oral, skin, respiratory, and systemic infections has not been well-studied. Fractions from whole cranberry fruit were screened for inhibition of five Candida species and Cryptococcus neoformans , a causative agent of fungal meningitis. Candida glabrata , Candida lusitaniae , Candida krusei , and Cryptococcus neoformans showed significant susceptibility to treatment with cranberry proanthocyanidin fractions in a broth microdilution assay, with minimum inhibitory concentrations as low as 1 mug/mL. MALDI-TOF MS analysis of subfractions detected epicatechin oligomers of up to 12 degrees of polymerization. Those containing larger oligomers caused the strongest inhibition. This study suggests that cranberry has potential as an antifungal agent.
Abstract: PURPOSE: To assess the effects of NDM from cranberries on Staphylococcus epidermidis biofilm formed on soft contact lenses.
METHODS: Soft contact lenses were incubated in Tryptic Soy Broth (TSB) together with S. epidermidis (ATCC35984/RP62A) and various concentrations of NDM, and inspected by scanning electron and confocal microscopy. The TSB was collected after sonification and monitored turbidometrically.
RESULTS: NDM at >=500 mug/mL concentration caused a significant (P < 0.01) reduction of biofilm. Scanning electron microscopy of biofilm in the presence of 500 to 1000 mug/mL NDM confirmed these results. In control lenses, multilayered mushroom-shaped biofilm and complete coverage of the lens surface were seen, whereas after incubation with 500 mug NDM per mL TSB, the biofilm was thinner with smaller protuberances, and exposed lens surface was partially seen. In samples incubated with 1000 mug NDM per mL TSB, the lens surface was clearly seen between sporadic microcolonies.
CONCLUSIONS: NDM reduces formation of biofilm on soft contact lenses. This has important implications for the prevention of contact lens-related corneal infections caused by S. epidermidis.
Abstract: Bacterial motility plays a key role in the colonization of surfaces by bacteria and the subsequent formation of resistant communities of bacteria called biofilms. Derivatives of cranberry fruit, predominantly condensed tannins called proanthocyanidins (PACs) have been reported to interfere with bacterial adhesion, but the effects of PACs and other tannins on bacterial motilities remain largely unknown. In this study, we investigated whether cranberry PAC (CPAC) and the hydrolyzable tannin in pomegranate (PG; punicalagin) affected the levels of motilities exhibited by the bacterium Pseudomonas aeruginosa. This bacterium utilizes flagellum-mediated swimming motility to approach a surface, attaches, and then further spreads via the surface-associated motilities designated swarming and twitching, mediated by multiple flagella and type IV pili, respectively. Under the conditions tested, both CPAC and PG completely blocked swarming motility but did not block swimming or twitching motilities. Other cranberry-containing materials and extracts of green tea (also rich in tannins) were also able to block or impair swarming motility. Moreover, swarming bacteria were repelled by filter paper discs impregnated with many tannin-containing materials. Growth experiments demonstrated that the majority of these compounds did not impair bacterial growth. When CPAC- or PG-containing medium was supplemented with surfactant (rhamnolipid), swarming motility was partially restored, suggesting that the effective tannins are in part acting by a rhamnolipid-related mechanism. Further support for this theory was provided by demonstrating that the agar surrounding tannin-induced nonswarming bacteria was considerably less hydrophilic than the agar area surrounding swarming bacteria. This is the first study to show that natural compounds containing tannins are able to block P. aeruginosa swarming motility and that swarming bacteria are repelled by such compounds.
Abstract: Traditional first-line treatment of chronic bacterial prostatitis (CBP) is administration of empirical antibiotics. However, the efficacy rate is low and long-term antibiotic therapy can result in adverse events and bacterial resistance. For these reasons, a new treatment or preventive modality that can replace traditional antibiotic therapy is required. There are several reports that E. coli extract has a preventive effect on recurrent urinary tract infection (UTI). Cranberries are also known to have beneficial effects in preventing UTI. To evaluate the preventive effect of E. coli extract and cranberries on CBP, 48 rats were randomly divided into 4 groups; control, ciprofloxacin, E. coli extract, and cranberry groups. All drug treatments were conducted for 3 weeks, and then we developed a CBP rat model. After 4 weeks, the results of microbiological culture of prostate and urine samples as well as histological findings for the prostate were analyzed for each group. The infection rate in the ciprofloxacin group was significantly lower than that in the control group. The microbiological cultures of the prostate and urine samples demonstrated reduced bacterial growth in all experimental groups compared with the control group. Histopathologic examination showed significantly decreased prostatic inflammation in all groups compared with the control group. These results suggest that E. coli extract has a potential preventive effect on the development of CBP, and cranberry also exhibits promising activity in this context
Abstract: The effects of the industrial juice process on the ability of neutralized cranberry samples and extracts (polar, apolar and anthocyanins) to inhibit the growth of Enterococcus faecium resistant to vancomycin (ERV), Escherichia coli O157:H7 EDL 933, E. coli ATCC 25922, Listeria monocytogenes HPB 2812, Pseudomonas aeruginosa ATCC 15442, Salmonella Typhimurium SL1344 and Staphylococcus aureus ATCC 29213 were investigated. The juice process appeared to have a general enhancing effect on the antibacterial properties of cranberry polar and anthocyanin extracts. The lowest minimum inhibitory concentrations (MICs) (1.80-7.0 micro g phenol/well) were obtained when S. aureus, S. Typhimurium, and ERV were exposed to the juice concentrate. The growth of P. aeruginosa, L. monocytogenes, E. coli ATCC, and E. coli O157:H7 was not inhibited by the juice concentrate, but did show sensitivity (maximal tolerated concentrations of 0.007-0.4 micro g phenol/well). The lowest MICs (22.6-90.5 micro g phenol/well) for P. aeruginosa, S. aureus, S. Typhimurium, and ERV were observed when they were exposed to the cranberry anthocyanin extract obtained from cranberry pomace. The results also showed a negative effect of the juice process on the antibacterial properties of the cranberry apolar extracts: the one obtained from frozen cranberries was most efficient against P. aeruginosa, S. aureus, L. monocytogenes and S. Typhimirium (MIC of 45.50 micro g phenol/well). The tested bacteria showed the greatest resistance toward the cranberry extracts obtained from the mash and the macerated and depectinized mash
Abstract: Transcriptional profiles of uropathogenic Escherichia coli CFT073 exposed to cranberry-derived proanthocyanidins (PACs) were determined. Our results indicate that bacteria grown on media supplemented with PACs were iron deprived. To our knowledge, this is the first time that PACs have been shown to induce a state of iron limitation in this bacterium.
Abstract: In humans, uropathogenic Escherichia coli (UPEC) is the most common etiological agent of uncomplicated urinary tract infections (UTIs). Cranberry extracts have been linked to the prevention of UTIs for over a century; however, a mechanistic understanding of the way in which cranberry derivatives prevent bacterial infection is still lacking. In this study, we used a fliC-lux reporter as well as quantitative reverse transcription-PCR to demonstrate that when UPEC strain CFT073 was grown or exposed to dehydrated, crushed cranberries or to purified cranberry-derived proanthocyanidins (cPACs), expression of the flagellin gene (fliC) was inhibited. In agreement with these results, transmission electron microscopy imaging of bacteria grown in the presence of cranberry materials revealed fewer flagella than those in bacteria grown under control conditions. Furthermore, we showed that swimming and swarming motilities were hindered when bacteria were grown in the presence of the cranberry compounds. Because flagellum-mediated motility has been suggested to enable UPEC to disseminate to the upper urinary tract, we propose that inhibition of flagellum-mediated motility might be a key mechanism by which cPACs prevent UTIs. This is the first report to show that cranberry compounds inhibit UPEC motility via downregulation of the fliC gene. Further studies are required to establish whether these inhibitors play a role in vivo.
Abstract: The various health benefits of Vaccinium macrocarpon (cranberry) are well documented and have been attributed mainly to its antioxidant capacity and anti-adhesive activity. Several different mechanisms have been proposed to explain the possible role of cranberries, cranberry juice, and cranberry extracts in inhibiting bacterial growth. These mechanisms of action (i.e., inhibition of the microbial growth) have not been thoroughly studied. Here, we took advantage of current advances in microarray technology and used GeneChip® Escherichia coli genome 2.0 arrays to gain insight into the molecular mechanisms involved in the impact of cranberry juice on the properties of E. coli growth. The inclusion of cranberry juice in bacterial growth media was found to significantly impact the doubling time of E. coli. The gene expression results revealed altered expression of genes associated with iron transport and essential metabolic enzymes as well as with adenosine triphosphate (ATP) synthesis and fumarate hydratase in these cultures. The altered expression of genes associated with iron transport was consistent with the strong iron chelating capability of proanthocyanidins, a major constituent of cranberry juice. The iron depletion effect was confirmed by adding exogenous iron to the growth media. This addition partially reversed the inhibitory effect on bacterial growth observed in the presence of cranberry juice/extracts.
Abstract: Background: The increasing prevalence of uropathogens resistant to antimicrobial agents has stimulated interest in cranberries to prevent recurrent urinary tract infections (UTIs). Methods: In a double-blind, double-dummy noninferiority trial, 221 premenopausal women with recurrent UTIs were randomized to 12-month prophylaxis use of trimethoprim-sulfamethoxazole (TMP-SMX), 480 mg once daily, or cranberry capsules, 500 mg twice daily. Primary end points were the mean number of symptomatic UTIs over 12 months, the proportion of patients with at least 1 symptomatic UTI, the median time to first UTI, and development of antibiotic resistance in indigenous Escherichia coli. Results: After 12 months, the mean number of patients with at least 1 symptomatic UTI was higher in the cranberry than in the TMP-SMX group (4.0 vs 1.8; P=.02), and the proportion of patients with at least 1 symptomatic UTI was higher in the cranberry than in the TMP-SMX group (78.2% vs 71.1%). Median time to the first symptomatic UTI was 4 months for the cranberry and 8 months for the TMP-SMX group. After 1 month, in the cranberry group, 23.7% of fecal and 28.1% of asymptomatic bacteriuria E. coli isolates were TMP-SMX resistant, whereas in the TMP-SMX group, 86.3% of fecal and 90.5% of asymptomatic bacteriuria E. coli isolates were TMP-SMX resistant. Similarly, we found increased resistance rates for trimethoprim, amoxicillin, and ciprofloxacin in these E. coli isolates after 1 month in the TMP-SMX group. After discontinuation of TMP-SMX, resistance reached baseline levels after 3 months. Antibiotic resistance did not increase in the cranberry group. Cranberries and TMP-SMX were equally well tolerated. Conclusion: In premenopausal women, TMP-SMX, 480 mg once daily, is more effective than cranberry capsules, 500 mg twice daily, to prevent recurrent UTIs, at the expense of emerging antibiotic resistance.
Abstract: Urinary tract infections (UTI) are common in childhood. In 30-50% of children with UTI the infections occur recurrently, especially in those with vesicoureteral reflux (VUR), neurogenic bladder (NB), previous cystitis or pyelonephritis and malformative uropathies. To reduce the likelihood of UTI, antibiotic prophylaxis has been regarded as the therapeutic standard for many years. However, the disadvantage of long-term antibiotic therapy is the potential for development of collateral effects and resistant organisms in the host. Such reasons have induced scientists to search for alternative modalities of UTI prevention and have contributed to determining the increasing desire for "naturalness" of the population and preventing excessive medication. The use of cranberry fulfils these needs by potentially replacing or enhancing traditional procedures. The purpose of this study was to assess the effectiveness of cranberry in preventing UTI in pediatric populations. We searched Pubmed, the Cochrane Central Register of Controlled Trials and Internet. Cranberry in patients with previous UTI was evaluated in three studies, cranberry in patients with VUR in three studies and four studies analyzed the efficacy of cranberry in children with NB. In seven of nine studies cranberry had a significant effect in preventing UTI.
Abstract: The glycosides of flavonoid, anthocyanins and A type proanthocyanidins in cranberry concentrate were characterized and quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Cranberry concentrate (1 g/body weight) was orally gavaged to Fischer-344 rats (n = 6), and blood and urine samples were collected over 24 h periods. Quercetin, 3'-O-methylquercetin (isorhamnetin), myricetin, kaempferol, and proanthocyanidin dimer A2, together with thirteen conjugated metabolites of quercetin and methylquercetin and intact peonidin 3-O-galactoside and cyanidin 3-O-galactoside were identified in the rat urine after cranberry treatment. Very low levels of isorhamnetin (0.48 +/- 0.09 ng/mL) and proanthocyanidin dimer A2 (0.541 +/- 0.10 ng/mL) were found in plasma samples after 1 h of cranberry administration. Although no quercetin was detected in plasma, MRM analysis of the methanolic extract of urinary bladder showed that chronic administration of cranberry concentrate to rats resulted in accumulation of quercetin and isorhamnetin in the bladder. These results demonstrate that cranberry components undergo rapid metabolism and elimination into the urine of rats and are present in the urinary bladder tissue potentially allowing them to inhibit urinary bladder carcinogenesis.
Abstract: This study investigated the effect of A-type cranberry proanthocyanidins (AC-PACs) on osteoclast formation and bone resorption activity. The differentiation of human pre-osteoclastic cells was assessed by tartrate-resistant acid phosphatase (TRAP) staining, while the secretion of interleukin-8 (IL-8) and matrix metalloproteinases (MMPs) was measured by ELISA. Bone resorption activity was investigated by using a human bone plate coupled with an immunoassay that detected the release of collagen helical peptides. AC-PACs up to 100 microg/mL were atoxic for osteoclastic cells. TRAP staining evidenced a dose-dependent inhibition of osteoclastogenesis. More specifically, AC-PACs at 50 microg/mL caused a 95% inhibition of RANKL-dependent osteoclast differentiation. This concentration of AC-PACs also significantly increased the secretion of IL-8 (6-fold) and inhibited the secretion of both MMP-2 and MMP-9. Lastly, AC-PACs (10, 25, 50 and 100 microg/ml) affected bone degradation mediated by mature osteoclasts by significantly decreasing the release of collagen helical peptides. This study suggests that AC-PACs can interfere with osteoclastic cell maturation and physiology as well as prevent bone resorption. These compounds may be considered as therapeutic agents for the prevention and treatment of periodontitis.
Abstract: Plant material screening was performed to study anti-Helicobacter pylori activity in vitro using an agar diffusion method on Columbia blood agar. 33 substances, juices and plant extracts and 35 of their combinations were tested. Quince (Cydonia oblonga) juice demonstrated the strongest anti-H. pylori activity followed by cranberry juice. Concentrated apple juice, plum, red currant, black chokeberry, raspberry and bilberry juice also showed significant activity. Green tea and apple pomace extract as well as sweet flag rhizome, ginger and wild bergamot extract, cherry syrup, red beet juice and whey did not exhibit anti-Helicobacter activity. Quince juice in combination with bilberry, black chokeberry, red currant juice, green tea, sweet flag rhizome or apple pomace extract as well as cranberry juice in combination with sweet flag rhizome extract demonstrated a synergistic effect on inhibition of H. pylori. The obtained results offer new perspectives for development of functional anti-Helicobacter food product(s) for dietary management of H. pylori infection. The essential components of these products could be the most active juices and extracts like quince and cranberry juice supplemented with a corresponding synergist. Further studies are required to investigate the mechanism of antibacterial action of plant products and their efficacy in vivo.
Abstract: The antimicrobial effect of cranberry juice and of three cranberry extracts (water-soluble (E1) and apolar phenolic compounds (E2), and anthocyanins (E3)) was investigated against seven bacterial strains (Enterococcus faecium resistant to vancomycin (ERV), Escherichia coli O157:H7 EDL 933, Escherichia coli ATCC 25922, Listeria monocytogenes HPB 2812, Pseudomonas aeruginosa ATCC 15442, Salmonella Typhimurium SL1344, and Staphylococcus aureus ATCC 29213). Each cranberry sample was analyzed to determine the minimum inhibitory concentration (MIC) and the maximal tolerated concentration (MTC) at neutral pH. The results, reported in micro g phenol/mL, indicated that all the bacterial strains, both Gram-positive and Gram-negative, were selectively inhibited by the cranberry phenolic compounds. The extract rich in water-soluble phenolic compounds caused the most important growth inhibitions. The bacteria ERV, and to a lesser degree, P. aeruginosa, S. aureus and E. coli ATCC 25922, were the most sensitive to the antimicrobial activity of extract E1. The growth of P. aeruginosa and E. coli ATCC was also affected by the presence of the anthocyanin-rich cranberry extract E3, although the observed antibacterial effect was not as important as with extract E1. In general, L. monocytogenes, E. coli O157:H7 and S. Typhimurium were the most resistant to the antibacterial activity of the cranberry extracts. Within 30 min of exposure with pure neutralized cranberry juice, L. monocytogenes and ERV were completely inactivated.
Abstract: Cranberry juice (CJ) and grape juice (GJ) from Vaccinium macrocarpon and Vitis labrusca, respectively, and purified proanthocyanidins (PACs) from these species are recognized to possess antiviral activity. The effects of CJ and GJ on tight junction (TJ) structure and function among rotavirus-infected monkey kidney epithelial cells (MA-104) in monolayer cultures were evaluated. Antiviral activity by cranberry PACs of rotavirus in cell-free suspension was investigated by a rotavirus antigen [i.e., viral capsid protein 6 (VP6)] capture enzyme-linked immunosorbent assay (ELISA) and by transmission electron microscopy (TEM). MA-104 monolayers were treated with CJ, GJ, or cranberry juice cocktail (CJC) drink before inoculation with rotavirus. TJ function and structural integrity were measured by changes in transepithelial electrical resistance (TEER) and by reduction of signal intensity of the TJ α-claudin 1 by immunofluorescence. The inhibitory activity of CJ and GJ on viral RNA synthesis, as a function of viral concentration, was determined by reverse transcription polymerase chain reaction (rtPCR). After 4 days, virus-infected monolayers pretreated with GJ (Concord and Niagara GJs) had TEER readings similar to uninfected controls. CJ and CJC also had a significant protective effect (P < 0.05) on TJ function, but to a lesser extent than GJ. Disorganization of TJ integrity commenced at 24- to 36-h post-viral inoculation, but this effect was reduced by pretreatment with CJ or GP of monolayer cultures. TEM showed aggregation of rotavirus by cranberry PACs. The destruction of rotavirus capsid proteins VP6, in cell-free suspension was inversely related to the concentration of cranberry PACs (C-PAC). Loss of rotavirus RNA by CJ or GJ was inversely related to viral infectivity titers. CJ, GJ, or PAC-associated antiviral activity has been linked to modifications in cellular physiologic events and to physical factors (e.g., PAC-mediated viral aggregation) that probably compromise viral infectivity. Multiple cell physiological and physical events must be considered when determining the mechanisms associated with the antiviral (i.e., rotavirus) activity of CJ, GJ, and PACs.
Abstract: The effects of cranberry juice cocktail (CJC) and proanthocyanidins (PACs) on biofilm formation were investigated. Escherichia coli strain HB101pDC1 and nonfimbriated strain HB101 were grown in 10 wt% CJC or 120 μg/mL PACs for 12 consecutive cultures. Biofilm formation was investigated by incubating bacteria in 96-well polyvinyl chloride (PVC) plates and studying the optical density of the solution using the crystal violet method. We suspect that biofilm formation occurred due to non-specific interactions between the bacteria and the polymer. Both P-fimbriated E. coli HB101pDC1 and the non-fimbriated strain HB101 formed biofilms. E. coli strain HB101pDC1 formed a thicker and more mature biofilm. Cranberry juice inhibited biofilm formation after the first culture; however, for bacteria grown in PACs, a decrease in biofilm formation was observed with increasing number of cultures. The inhibitory effect was reversible. These results demonstrate that CJC is more effective than isolated PACs at preventing biofilm formation, possibly suggesting that other cranberry compounds also play a role in anti-biofilm activity.
Abstract: Twenty-seven patients with indwelling urinary catheters and chronic bacteriuria were studied for methenamine efficacy. In a crossover fashion, each patient received methenamine mandelate granules 4 g/day alone, with ascorbic acid 4 g/day, and with ascorbic acid 4 g/day plus cranberry cocktail one 1/day. Proteus vulgaris, Pseudomonas aeruginosa, and E. coli were the common pathogens. Urinary acidifiers had no significant effect on mean urine pH, however, high urinary formaldehyde concentrations were associated with the use of ascorbic acid. Bacteriocidal formaldehyde levels were more frequently present in patients with acidic urine pH than those with alkaline pH. Although ascorbic acid increased formaldehyde levels, additional cranberry cocktail had no further effect. Despite higher formaldehyde levels, urine culture results were positive in most cases with or without urine acidification. Methenamine therapy may be of limited value in asymptomatic chronic bacteriuric patients with indwelling catheters.
Abstract: This study involved 27 geriatric patients with asymptomatic chronic bacteriuria; all had indwelling Foley catheters. The treatment regimens (daily oral dosage) were: methenamine mandelate (MM) granules, 4 gm; MM, 4 gm, plus ascorbic acid, 4 gm; and MM, 4 gm, plus ascorbic acid, 4 gm, plus cranberry cocktail, 1 liter--administered according to a cross-over design. Proteus vulgaris, Pseudomonas aeruginosa and E. coli were the most common urinary organisms. Proteus organisms were more often found in alkaline than in acidic urines, but the type of pathogen had no influence on urinary pH. Urinary formaldehyde concentration [HCHO] was lower in patients with Proteus infection (17.7 micrograms/ml) than in those with Pseudomonas (21.9 micrograms/ml) or E. coli infection (21.8 micrograms/ml). However, for Proteus infection, [HCHO] was higher in patients receiving MM plus ascorbic acid than in those receiving MM alone. Addition of cranberry cocktail to ascorbic acid did not enhance urinary pH, [HCHO] or methenamine efficacy. Our data suggest that in Foley catheter patients with chronic asymptomatic bacteriuria secondary to Proteus, Pseudomonas or E. coli infection, the type of urinary pathogen or the urinary pH cannot be used to predict the efficacy of methenamine therapy either with or without urinary acidifying agents.
Abstract: Bacterial adhesion to the cell surface is a crucial step before infection can take place. Inhibition of bacterial binding offers a novel preventive approach against infections. Cranberry (Vaccinium macrocarpon Ait.) juice has been found to have antiadhesive activity against different bacteria. Streptococcus pneumoniae is an important pathogen and the most common cause for pneumonia, meningitis, and otitis media. In this study the inhibitory activity of cranberry (Vaccinium oxycoccos L.), bilberry (Vaccinium myrtillus L.) and crowberry (Empetrum nigrum and Empetrum hermaphroditum L.) juice fractions against pneumococcal binding was tested using human bronchial cells (Calu-3) as an adhesion model. In addition, the antimicrobial activity of the berry juice fractions was tested. It was found that the studied berry juice fractions had antiadhesion activity and cranberry juice was the most active. The adhesion inhibition activity of cranberry juice was nearly 90% at a concentration of 8.7mg/g of soluble solids. The antimicrobial activity of the studied berry juice fractions was found to be remarkable; pneumococcal growth was inhibited totally at a concentration of ~86mg/g. Both antiadhesion and antimicrobial activities were reduced after solid-phase extraction of the berry juices, which may suggest molecular synergistic effects of the berry juice molecules against S. pneumoniae. The findings indicate that cranberry, bilberry and crowberry juices have potential against pneumococcal infections.
Abstract: The in vitro effectivity of cranberry derived proanthocyanidins (PACs) for the mitigation of kidney cell
infection by selected uro- and entero-pathogens is examined with an adhesion/invasion assay and confocal
microscopy. This study demonstrates that PACs effectively reduce invasion of canine kidney cells by
pathogenic bacteria: Escherichia coli CFT073 and O157:H7, Enterococcus faecalis 29212, and Pseudomonas
aeruginosa 10145. These effects demonstrate the potential for cranberry derived PACs as a useful tool in
the prevention of kidney infection
Abstract: We studied the relation between sexual and health behaviors of women and first-time urinary tract infection (UTI). The study population was women using a university health service who were unmarried, had no UTI history, and who had engaged in sexual activity at least once. We found 86 cases of UTI, defined as one or more urinary symptoms and ^1,000colony-forming units per ml urine of a known pathogen. We randomly sampled 288 controls from the student body. Vaginal intercourse increased the risk of UTI; this risk was further increased with condom use. After adjusting for vaginal intercourse with other birth control methods and recentness of current sexual partnership, a single sex act with a condom in the past 2 weeks increased UTI risk by 43%. Having a sex partner for less than 1 year vs 1 year or more, after adjustment for frequency of vaginal intercourse and birth control method, was associated with about twice the risk of UTI [odds ratio (OR) = 1.97; 95% confidence interval (CI) = 1.04-3.74].After adjusting for frequency of vaginal intercourse, regular drinking of cranberry juice was protective against UTI (OR =
0.48; 95% CI = 0.19-1.02), whereas drinking carbonated soft
drinks appeared to be associated with increased risk (OR =
2.37; 95% CI = 0.75-7.81). Using deodorant sanitary napkins
or tampons was associated with a slight increase in risk of UTI (OR = 1.51; 95% CI = 0.74-3.06). Blacks had five times
greater risk of UTI than whites after adjusting for frequency of vaginal intercourse (OR = 5.2; 95% CI = 1.89-24.63). We
observed only modest differences in health behavior between racial groups.
Abstract: Cranberries have long been the focus of interest for their beneficial effects in preventing urinary tract infections (UTIs). The objective of this study was to determine in vitro activity of cranberry extract on common etiologic agents of urinary tract infections isolated from patients. Filter sterilized methanol extract of cranberry was prepared and used in the present study. The minimum inhibitory concentration (MIC) was evaluated for active crude extract. The MIC value of methanol extract were 0.391 mg/ml for
Enterobacter aerogenes and Staphylococcus aureus whereas the MIC of methanol extract of cranberry were 1.2500 and 0.0195 mg/ml for Escherichia coli and Klebsiella pneumoniae respectively. The lower MIC value of cranberry extract against K. pneumoniae in comparison to other three organisms suggests that K. pneumoniae showed greater sensitivity towards the extracts of the cranberry extract.
Abstract: The treatment of chronic pelvic pain syndrome (CPPS) is based on antibiotic therapy, but many patients experience a relapse after treatment. Cranberry juice is known for its roles in both the treatment and prevention of urinary tract infections. This study was performed to evaluate the effectiveness of cranberry juice in the prevention of a relapse after the treatment of CPPS.
Materials and Methods: Fifty patients, diagnosed as CPPS (National Institutes of Health; NIH-catagory IIIa), were included in this study. All the patients had initially been treated with levofloxacin and supportive treatment for 8-12 weeks. After completion of the initial treatment, 26 olunteer patients were recommended to drink 150ml of cranberry juice twice a day, 24 patients, as a control group, received no cranberry juice and all the patients re-evaluated after 3 months. Results: On initial diagnosis, the white blood cell (WBC) count in the high power field (HFP) of expressed prostatic secretions (EPS) and the NIHChronic
Prostatitis Symptom Index (NIH-CPSI) in cranberry group were 18.2±3.4 and 23.1±4.4 and those of the control group 16.4±4.8 and 22.4±3.7, respectively. When the medical treatment was ended, the WBC of the EPS and NIH-CPSI in the cranberry group were 2.5±2.1 and 14.1±4.1, and those of the control group were 2.7±1.9 and 13.7±2.1, respectively. After the three month follow-up, the cranberry group showed a WBC of 2.2±2.5 in the EPS and a NIH-CPSI of 12.7±3.9, a slight decrease or similar result compared to the treatment completion period. No patient showed aggravation of symptoms after drinking cranberry juice, whereas five from the control group did. Conclusions: Cranberry juice showed an effect in the prevention of a relapse in CPPS patients, with no adverse effects.
Abstract: Ethyl acetate extracts of Sephadex LH20-purified proanthocyanidins of American cranberry (Vaccinium macrocarpon Ait.) exhibited potent biological activity by inhibiting adherence of uropathogenic isolates of P-fimbriated Escherichia coli bacteria to cellular surfaces containing a-Gal(1 4 4)b-Gal receptor sequences similar to those on epithelial cells in the urinary tract. The chemical structures of the proanthocyanidins were determined by 13C NMR, electrospray mass spectrometry, matrix-assisted
laser absorption time-of-flight mass spectrometry and by acid catalyzed degradation with phloroglucinol. The proanthocyanidin molecules consisted predominantly of epicatechin units with mainly DP of 4 and 5 containing at least one A-type linkage. The procyanidin A2 was the most common terminating unit occurring about four times as frequently as the epicatechin monomer
Abstract: Cranberry and its products are important components of the cranberry processing industry and have historically been associated with positive health benefits such as preventing urinary tract infections. These health benefits are associated with phenolic phytochemicals in the juice which are now known to have potential for inhibition of development and progression of cancer and cardiovascular diseases. Helicobacter pylori is an important human pathogen linked to peptic ulcer and now to cardiovascular diseases. Control of this pathogen using synthetic antimicrobials such as currently approved antibiotics has limitations due to potential development of resistance and low compliance. We believe a profile of antimicrobials compared to a single compound could be potentially more effective in managing H. pylori infections. We have investigated the effect of cranberry, blueberry and grape seed extracts on inhibiting H. pylori have been investigated. The ability of blueberry, grape seed and oregano extract on enhancing the antioxidant and anti-H. pylori activity of cranberry powder in a mixture was also investigated. The anti-H. pylori activity of the cranberry fruit extracts and their synergies correlated with antioxidant activity and the presence of biphenyls as well as polyphenolic phytochemicals. The anti-H. pylori activity of cranberry juice extract was significantly improved by its synergistic blending with blueberry, grape seed and oregano extract. The lower efficacy of purified phenolics in inhibiting H. pylori compared with fruit powder at similar dosage levels suggests a synergistic mode of functionality of these individual phenolics in whole food background. Consumption of blends of fruit juices with other fruit as well as herb extracts can impart unique functional attributes and could be an effective strategy in developing diet-based management of H. pylori infections as well as other oxidation linked diseases.
Abstract: Cranberry fruit is a rich source of polyphenols, and has shown biological activities against Streptococcus mutans. In the present study, we examined the influence of extracts of flavonols (FLAV), anthocyanins (A) and proanthocyanidins (PAC) from cranberry on virulence factors involved in Streptococcus mutans biofilm development and acidogenicity. PAC and FLAV, alone or in combination, inhibited the surface-adsorbed glucosyltransferases and F-ATPases activities, and the acid production by S. mutans cells. Furthermore, biofilm development and acidogenicity were significantly affected by topical applications of PAC and FLAV (P<0.05). Anthocyanins were devoid of any significant biological effects. The flavonols are comprised of mostly quercetin glycosides, and the PAC are largely A-type oligomers of epicatechin. Our data show that proanthocyanidins and flavonols are the active constituents of cranberry against S. mutans.
Abstract: Several studies have shown the antimutagenic DNA protective functions of some naturally occurring phenolic phytochemicals. Emerging research also indicates that synergistic functionality of these phytochemicals in whole foods benefits the management of many diseases. This study investigated the potential antimutagenic properties of cranberry phenolics, ellagic acid (EA), rosmarinic acid (RA) and their synergistic interactions on enhancing the antimutagenic properties in Salmonella typhimurium tester system against the mutagens sodium azide and N-methyl-N'-nitro-N-nitrosoguanidine. The ability of these phytochemical treatments to protect oxidative damage to DNA was also investigated using the supercoiled DNA strand scission assay. The results showed that EA was most effective in inhibiting the mutations in S. typhimurium system, whereas RA and EA were equally effective in protecting the DNA from oxidative damage. In addition, the antimutagenic activity of cranberry powder (CP) made from juice extracts was significantly enhanced when 30% (w/w) of phenolics in CP was substituted with RA and EA, possibly because of synergistic redox modulation that can influence mutagen function. It was also suggested that the synergistic mixture of cranberry phenolics with RA could also be protecting the cell from mutations by modulating the DNA repair systems
Abstract: Cranberry cocktail has been reported to reduce bacteriuria and pyuria in elderly women and self-reported urinary tract infection (UTI) in young female undergraduates, but commercially prepared cranberry concentrate supplements have never been evaluated in multiple sclerosis (MS) patients with neurogenic bladder. The purpose of this study was to determine whether one 8,000-mg cranberry concentrate supplement daily could prevent UTI in MS participants with bladder symptoms. We conducted a double-blind, randomized, placebo-controlled longitudinal trial of cranberry supplement versus placebo with participants who have MS. After informed consent had been obtained from the participants, baseline data were collected and participants were randomized to receive either one cranberry supplement or placebo daily for 6 months. The sample consisted of 135 participants. In the cranberry group 34.6% of participants failed (i.e., developed a UTI) versus 32.4% in the control group (p = .849). Not all cranberry supplements have been found to contain proanthocyanidins, the active ingredient of cranberries. Because there is no way for the consumer to distinguish supplements that contain proanthocyanidins from those that do not, taking juice or whole cranberries may be preferrable.
Abstract: Cranberry, the fresh or dried ripe fruit of Vaccinium macrocarpon Ait. (Ericaceae), is currently used as adjunct therapy for the prevention and symptomatic treatment of urinary tract infections. Data from clinical trials suggest that extracts of cranberry or cranberry juice reduce the bacterial load of E. coli and also suppress the inflammatory symptoms induced by E. coli infections. A methanol extract prepared from 10 kg of dehydrated cranberries did not directly inhibit the growth of E coli strains ATCC 700336 or ATCC 25922 in concentrations up to 256 mug/mL in vitro. However, the methanol extract (CR-ME) inhibited the activity of cyclooxygenase-2, with an IC(50) of 12.8 mug/mL. Moreover, CR-ME also inhibited the NF-kappabeta transcriptional activation in human T lymphocytes with an IC(50) of 19.4 mug/mL, and significantly (p < 0.01) inhibited the release of interleukin (IL)-1beta, IL-6, IL-8 and tumor necrosis factor-alpha from E. coli lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells in vitro, at a concentration of 50 mug/mL. The extract had no effect on inducible nitric oxide synthase activity in the murine macrophage cell line RAW 264.7. The compounds responsible for this activity were identified using a novel LC-MS based assay as ursolic acid and ursolic acid derivatives. Taken together, these data suggest CR-ME and its constituent chemical compounds target specific pathways involved in E. coli-induced inflammation.
Abstract: Background. A number of observational studies and a few small or open randomized clinical trials suggest that
the American cranberry may decrease incidence of recurring urinary tract infection (UTI).
Methods. We conducted a double-blind, placebo-controlled trial of the effects of cranberry on risk of recurring
UTI among 319 college women presenting with an acute UTI. Participants were followed up until a second UTI or
for 6 months, whichever came first. A UTI was defined on the basis of the combination of symptoms and a urine
culture positive for a known uropathogen. The study was designed to detect a 2-fold difference between treated and
placebo groups, as was detected in unblinded trials. We assumed 30% of participants would experience a UTI during
the follow-up period.
Results. Overall, the recurrence rate was 16.9% (95% confidence interval, 12.8%–21.0%), and the distribution
of the recurrences was similar between study groups, with the active cranberry group presenting a slightly higher
recurrence rate (20.0% vs 14.0%). The presence of urinary symptoms at 3 days, 1–2 weeks, and at >1 month was
similar between study groups, with overall no marked differences.
Conclusions. Among otherwise healthy college women with an acute UTI, those drinking 8 oz of 27% cranberry
juice twice daily did not experience a decrease in the 6-month incidence of a second UTI, compared with those
drinking a placebo.
Abstract: CONTEXT: Cranberry juice has long been recognized in folk medicine as a therapeutic agent, mainly in urinary tract infections. Its proposed mechanism of action is antiadhesion of bacteria.
OBJECTIVE: Investigation of the potential antiadhesion effect of nondialyzed material of cranberry (NDM) via its influence on secretion, gene expression, and promoter activity of the fructosyltransferase (FTF), which is among the extracellular enzymes associated with dental biofilm formation and pathogenesis of oral bacteria.
MAIN OUTCOME MEASURES: Secretion of FTF from Streptococcus mutans, in the presence of NDM, was measured by immunoblotting and confocal scanning laser microscopy. Its influence on ftf gene expression was determined by reverse transcription followed by real-time RT-PCR. The luciferase assay was used to detect bioluminescence expressed by the ftf promoter activity of bacteria exposed to NDM.
RESULTS: NDM at concentrations between 0.2/mL and 1mg/mL significantly (P<.05) decreased secretion of extracellular FTF, as well as down-regulated ftf expression in a dose-dependent manner. NDM also markedly reduced the luciferase activity under the ftf promoter.
Abstract: Cranberry juice has long been recognized in folk medicine as a therapeutic agent, mainly in urinary track infections. It acts as an antibiofilm agent against various pathogens. Quorum sensing is process where bacteria communicate with each other via signal molecules known as autoinducers. This process is strongly involved in various bacterial pathological and physiological pathways. Various strains of Vibrio harveyi bacteria were incubated with different concentrations of nondialyzable material of cranberry (NDM) with or without addition of exogenous autoinducer. Bioluminescence regulated by the autoinducers was measured in GENios reader. Effect of NDM alone or NDM supplemented with autoinducer on quorum sensing was determined as change in bioluminescence in each treated sample compared to appropriate control in every strain. Using model of V. harveyi, we found an inhibitory effect of cranberry constituents on bacterial signaling system. This effect was reversible, since exogenous autoinducer was able to recover bioluminescence which was decreased by NDM. We hypothesized that cranberry NDM interacts with V. harveyi quorum sensing by competition with autoinducer
Abstract: PURPOSE: Vaccinium macrocarpon--the American cranberry--irreversibly inhibits the expression of P-fimbriae of E. coli. Further effects on the function and expression of P-fimbriae were studied by growing P-fimbriated E. coli in solid media laced with cranberry juice.
METHODS: Cranberry concentrate at pH 7.0 was added to CFA medium to a final concentration of 25%. E. coli strains JR1 and DS17 were plated on this medium with a plain CFA control and incubated at 37C. Cultures were tested for ability to agglutinate P-receptor specific beads. Bacteria were washed in PBS and agglutination retested. Cultures were also replated on plain CFA agar and rechecked for their ability to agglutinate. Transmission electron micrographs were performed on positive control and test bacteria.
RESULTS: For E. coli strain JR1, P-fimbrial agglutination was inhibited after the third plating. DS17 was fully inhibited after the second plating. Washing in PBS did not affect agglutination, but replating on CFA agar allowed agglutination to recur. Electron micrographic study of control populations confirmed fimbriae. Fully inhibited bacteria had a 100% reduction in expression of fimbriae. Additionally, inhibited bacteria showed cellular elongation.
CONCLUSIONS: Cranberry juice irreversibly inhibits P-fimbriae. Electron micrographic evidence suggests that cranberry juice acts on the cell wall preventing proper attachment of the fimbrial subunits or as a genetic control preventing the expression of normal fimbrial subunits or both.
Abstract: Because previous studies have shown that a high molecular mass constituent of cranberry juice inhibited adhesion of Escherichia coli to epithelial cells and coaggregation of oral bacteria, we have examined its effect on the adhesion of Helicobacter pylori to immobilized human mucus and to erythrocytes. We employed three strains of H. pylori all of which bound to the mucus and agglutinated human erythrocytes via a sialic acid-specific adhesin. The results showed that a high molecular mass constituent derived from cranberry juice inhibits the sialic acid-specific adhesion of H. pylori to human gastric mucus and to human erythrocytes.
Abstract: In the 20th century, the health benefit most often attributed to the cranberry is its role in maintaining urinary-tract health. A 1998 study by the International Food Information Council (personal communication) indicated that 47% of consumers surveyed were aware of a link between cranberry juice and urinary-tract health.
Abstract: Twenty-one female and 19 male subjects who had normal physical and laboratory examinations were randomly assigned into four groups of 10 subjects each. Each group was then randomly assigned a number (150, 180, 210, 240) which determined the amount of cranberry juice, in milliliters, members of that group would ingest with each meal during the experimental phase of the study. The study took place over a 12-day period. A one-group before-and-after design was used, with each subject serving as his or her own control. Diet was controlled; menus on days 1 through 6 were repeated on days 7 through 12 with the addition of cranberry juice at each meal. Subjects used nitrazine pH tape to measure the pH of midstream urine at each voiding. There were significant (.01 level) differences in mean urinary pH between each control group and its corresponding experimental group. Anticipated problems with increased number of bowel movements, weight gain, increased voiding frequency, and subject pH measurement inaccuracy did not occur.
Abstract: Most research suggests that ingestion of cranberry juice may be useful in preventing urinary tract infections. This pilot study examines the effect of drinking moderate amounts of commercially available cranberry juice cocktail on urinary pH in older, institutionalized adults. The results of the study have implications for home care nurses who have similar patients in their case loads.
Abstract: The purpose of this study was to quantitate the effect of cranberry juice ingestion on urinary acidification and calcium excretion, in a diet-controlled situation.
Abstract: The influence of diet on aryl acid metabolism was determined in normal and azotemic subjects. Aryl acid content of serum and urine was estimated by fluorometry in relation to hippuric acid as a standard (FI-Hipp). Secretory activity, a reflection of the biological potency of aromatic acids in serum and urine, was determined by bioassay. The urinary excretion of FI-Hipp and secretory activity of five normal persons on an ad lib diet was 0.78 and 2.25 mM/day, respectively; similar values were observed in two subjects with chronic renal insufficiency. Subjects were fed prunes and cranberries, since these foods contain abundant quantities of hippurate precursors. Prunes 1.5 g/kg body weight, caused the urinary excretion of both FI-Hipp and secretory activity to increase about tenfold in normal and azotemic subjects. Prune feeding caused the serum levels of FI-Hipp and secretory activity to increase about threefold. Cranberries increased the renal excretion of FI-Hipp and secretory activity as did the ingestion of a beverage containing benzoate as a preservative. On the basis of these studies it is clear that diet is an important determinant of the load of aryl acids for urinary excretion; in patients with renal insufficiency the ingestion of foods containing precursors may cause serum level of biologically active aryl acids to increase strikingly.
Abstract: Bacterial surface properties, such as electrostatic potential play an important role in the bacterial adhesion process, which is widely considered as the first step leading to infections. Cranberry juice and its compound A-type proanthocyanidins (PACs) were used to treat two isogenic E. coli strains and human uroepithelial cells and the zeta potentials were measured at several cranberry juice or PACs concentrations. P fimbriae were shown to be slightly positively charged, which helps bacteria adhere onto mammalian cells. PACs significantly decreased the bacterial zeta potentials from -15.6 ± 0.9 mV to -41.5 ± 0.7 mV, which increased the electrostatic repulsion forces to mammalian cells. Cranberry juice treatment did not change bacterial zeta potentials significantly, ranging from -14.9 ± 1.8 mV to -16.3 ± 0.8 mV. The abundance of other compounds in cranberry juice may have blocked the influence of PACs, considering the relatively small proportion of PACs in cranberry juice.
Abstract: An extract from fresh cranberries was shown to decrease the strength of attachment of Escherichia coli to glass coverslips when incubated together for 2 h. Pre-conditioning of the surface prior to biofilm formation also significantly weakened the strength of attached cells.
Abstract: BACKGROUND: The inhibition of Escherichia coli growth in the presence of Vaccinium macrocarpon has been extensively described; however, the mechanisms of this activity are not well characterized.
FINDINGS: Here, E. coli was grown in media spiked with cranberry juice. The growth rate and media pH were monitored over more than 300 generations. The pH of the growth media was found to decrease during cell growth. This result was unique to media spiked with cranberry juice and was not reproduced through the addition of sugars, proanthocyanidins, or metal chelators to growth media.
CONCLUSION: This study demonstrated that factors other than sugars or proanthocyanidins in cranberry juice result in acidification of the growth media. Further studies are necessary for a complete understanding of the antimicrobial activity of cranberry products.
Abstract: An ethanolic extract of Cranberry exerted a significant antimicrobial effect on Saccharomyces bayanus and Pseudomonas fluorescens. The antimicrobial properties of cranberries were due to a number of factors. First, the low pH (2.6) inhibited many microorganisms per se, and its effect on the dissociation of benzoic acid made the inhibition more drastic. Secondly, after raising the pH to 5.2, cranberry juice still did not support the growth of S. bayanus. Growth did occur at pH 5.2 after 0.3% yeast nitrogen base was added. Thirdly, proanthocyanidins and flavonols were found to be the major microbial inhibitors other than benzoic acid. The results showed that proanthocyanidins provided 21.3% of the inhibition, the flavonols 18.5% and benzoic acid 15.6%.
Abstract: Cranberry juice has developed a following as a simple, nonpharmacologic means to reduce or treat urinary tract infections, yet the scientific basis for such a claim has been lacking. A new study suggests that bacterial infections (bacteriuria) and associated influx of white blood cells into the urine (pyuria) can be reduced by nearly 50% in elderly women who drink 300 mL of cranberry juice cocktail each day over the course of a 6-month study. The results of this study suggest that consumption of cranberry juice is more effective in treating than preventing bacteriuria and pyuria. Along with earlier reports on the ability of cranberry juice to inhibit bacterial adherence to urinary epithelial cells in cell culture, this new work suggests that drinking cranberry juice each day may be clinically useful. Additional work must be conducted, however, to more completely define the efficacy of cranberry juice.
Abstract: OBJECTIVES: To determine the safety, tolerability, maximal tolerated dose, and efficacy of a concentrated cranberry liquid blend, UTI-STAT with Proantinox, in female patients with a history of recurrent urinary tract infections (rUTIs).
METHODS: The study agent was administered orally at 15, 30, 45, 60, and 75 mL daily for 12 weeks to women with a history of 2.78 ± 0.73 rUTIs <6 months. Blood and urine samples were collected at baseline and weeks 4 and 12. The women took daily doses of the agent. The primary endpoints were the safety, tolerability, and maximal tolerated dose. The secondary endpoints were the efficacy with regard to rUTI and quality-of-life (QOL) symptoms.
RESULTS: A total of 28 subjects were included in the study. Of these 28 women, the data from 23 were analyzable. The average age was 46.5 ± 12.8 years. The maximal tolerated dose of UTI-STAT was 75 mL/d, and the recommended dose was set at 60 mL/d. The secondary endpoints demonstrated that only 2 (9.1%) of 23 reported a rUTI, a markedly better rate than the historical data. At 12 weeks, the reduction in worry about rUTIs and increased QOL with regard to the physical functioning domain and role limitations from physical health domain, as measured by the Medical Outcomes Study short-form 36-item questionnaire, were significant (P = .0097). A lower American Urological Association Symptom Index indicating greater QOL was also significant (P = .045).
CONCLUSIONS: The novel concentrated cranberry liquid blend showed a good safety profile and tolerability in both pre- and postmenopausal women with history of rUTIs. The secondary endpoints demonstrated its effectiveness in reducing the incidence of rUTI and increasing QOL. Given this evidence, supplementation might be beneficial in the prevention of rUTIs in this population.
Abstract: In this study, urine was collected from groups of volunteers following the consumption of water, ascorbic acid, or cranberry supplements. Only ascorbic acid intake consistently produced acidic urine. Photospectroscopy data indicated that increased water consumption produced urine with lower protein content. Surface tension measurements of the collected urine showed that both water and cranberry supplementation consistently produced urine with surface tensions higher than the control or urine collected following ascorbic acid intake. These urine samples were also employed to study uropathogen adhesion to silicone rubber in a parallel plate flow chamber. Urine obtained after ascorbic acid or cranberry supplementation reduced the initial deposition rates and numbers of adherent Escherichia coli and Enterococcus faecalis, but not Pseudomonas aeruginosa, Staphylococcus epidermidis, or Candida albicans. Conversely, urine obtained from subjects with increased water intake vastly increased the initial deposition rates and numbers of adherent E. coli and E. faecalis (P < 0.05).
Abstract: The objective of the study was to evaluate liquid cranberry products as prophylaxis against bacterial urinary tract infection in a pediatric neuropathic bladder population. Forty cases managed by clean intermittent catheterization with or without pharmacotherapy were enrolled in a randomized single-blind cross-over study. Subjects ingested 15 mL/kg/day of cranberry cocktail or water for six months followed by the reverse for another six months. Initial catheter urine samples and subsequent monthly and interim cultures were obtained. Associated symptoms were recorded along with follow-up attendance/compliance registry. The number of negative culture months to the number of months contributed was tabulated and compared between interventions. Individual, cumulative and antimicrobial subset analysis was performed. Twenty one patients completed the study;12 dropped out for reasons related to the cranberry (taste, caloric load and cost); seven patients dropped out for other reasons (parents too busy, death, no stated reason). Wilcoxon matched-pairs Signed-ranks analysis revealed no difference between intervention periods (2-tailed P=.5566 [whole group]; p=.2845 [antimicrobial subset]) with respect to infection. Fewer infections were observed in nine patients taking cranberry juice and in nine patients given water; no difference was noted in three. Liquid cranberry products, on a daily basis, at the dosage employed, did not have any effect greater than that of water in preventing urinary tract infections in this pediatric neuropathic bladder population.
Abstract: No abstract
Abstract: STUDY DESIGN: A pilot study of 15 spinal cord injured patients. Objective: To determine whether alteration of fluid intake and use of cranberry juice altered the bacterial biofilm load in the bladder. SETTING: London, Ontario, Canada. METHODS: Urine samples were collected on day 0 (start of study), on day 7 following each patient taking one glass of water three times daily in addition to normal diet, and on day 15 following each patient taking one glass of cranberry juice thrice daily. One urine sample was sent for culture and a second processed to harvest, examine by light microscopy and Gram stain non-squamous uroepithelial cells to generate bacterial adhesion per 50 cells data. RESULTS: The results showed that cranberry juice intake significantly reduced the biofilm load compared to baseline (P=0.013). This was due to a reduction in adhesion of Gram negative (P=0.054) and Gram positive (P=0.022) bacteria to cells. Water intake did not significantly reduce the bacterial adhesion or biofilm presence. CONCLUSION: The findings provide evidence in support of further, larger clinical trials into the use of functional foods, particularly cranberry juice, to reduce the risk of UTI in a patient population highly susceptible to morbidity and mortality associated with drug resistant uropathogens
Abstract: No abstract - Methods: We tested a 5-fold concentrated preparation of the juice to simulate the cranberry concentrate currently available commercially. The concentrate was diluted 1:1 with trypticase soy broth and adjusted to a pH of 7.0 to ensure that the results would not be confounded by the acidity of the medium. We added an inoculum of approximately 104 colony-forming units per milliliter from an overnight culture of a variety of American Type Culture Collection–quality control strains both to plain broth and the broth to which the cranberry juice had been added. Both cultures were incubated at 35°C and bacterial counts performed in duplicate at 90 minutes and 24 hours.
Abstract: OBJECTIVES: The American cranberry proanthocyanidins (PACs) are the main responsible for its efficacy in urinary tract infections. Their mechanism of action is related to inhibition of Escherichia coli to urothelial cells. Cysticlean contains an extract of American cranberry which provides 118 mg of PACs per dose. The activity of Cysticlean tablets on Escherichia Coli adherence to bladder epithelial cells has been studied in vitro. Moreover, the activity of Cistyclean both in powder for oral suspension and tablets has been compared ex-vivo. METHODS: The rats received both Cysticlean preparations per orem, and urine from each animal was collected during the following 16 hours and preincubated with E. coli. Subsequently, bacteria were incubated with T24 cells. After 1 hour the number of bacteria adhered per cell was calculated. For the in vitro study, E. Coli preincubated at various concentrations of the products were incubated with T24 cells and the same process previously referred was carried out. RESULTS: Urine samples from rats taking Cysticlean powder for oral suspension and tablets (118 mg PACs/animal) showed an important inhibition of E. Coli adherence (83% and 52%respectively). The inferior dose of 59 mg PACs/animal also showed marked inhibition of E. Coli adherence (29% after Cysticlean tablets intake and 40% for powder). In vitro, Cysticlean showed inhibition of bacterial adherence in all tested concentrations: 5, 25 and 75 PACs mg/ml, diminishing the number og bacteria adhered to epithelial cells by 25%, 36% and 34% respectively. CONCLUSIONS: Cysticlean shows a significant inhibition of E. Coli adherence to urothelial cells. Cysticlean powder for suspensión preparation is more effective tha tablets. Cysticlean powder for suspensión is well tolerated, and compliance has been observed. Its use is very recommendable in pediatric urinary tract infection prophylaxis. Due to the variety of products with American cranberry extracts in the market, with different proanthocyanidins declared content, it would be interesting to compare their activity using established pharmacological methods.
Abstract: Ascorbic acid and hippuric acid (from cranberry juice) are commonly used to acidify the urine for the purpose of enhancing the degradation of therapeutic methenamine mandelate to urinary formaldehyde. A study was made of 27 nondiabetic geriatric patients with indwelling Foley catheters and chronic bacteriuria who were treated with methenamine mandelate (4 gm), ascorbic acid (4 gm), and cranberry cocktail (1 liter) daily. All of 972 urine samples showed formaldehyde in mean concentrations between 14 and 25 microgram/ml. No glucose was found when the urine was tested by the copper-reduction method. In vitro false positive reactions reported in the literature do not appear to be duplicated as an in vivo problem.
Abstract: AIMS: The aim of the study was to assess whether the oral intake of cranberry juice cocktail compared with apple juice was associated with a significant difference in urinary symptoms experienced during radical external beam radiation therapy (EBRT) for prostate carcinoma. MATERIALS AND METHODS: One hundred and twelve men with prostate cancer were randomised to either 354 ml cranberry juice or apple juice a day. Stratification was based on a history of a previous transurethral resection of prostate (TURP yes/no) and baseline International Prostate Symptom Score (IPSS < 6 or > or = 6) of urinary symptoms. RESULTS: The maximum IPSS (MRT) and the maximum change in IPSS from baseline (DRT) are used to report the results. We analysed the effects of juice allocation on DRT and MRT using analysis of covariates (ANCOVA). We observed no significant difference for DRT (P = 0.39) or MRT (P = 0.76) related to the consumption of cranberry compared with apple juice. However, we found a significant relationship between the history of a previous TURP and both DRT (P = 0.01) and MRT (P = 0.01). The history of a previous TURP was associated with lower values for both end points. Baseline IPSS was significant for DRT (P = 0.004) and MRT (P < or = 0.001). We found a significant relationship between the baseline IPSS < 6 or > or = 6 cut point on MRT (P < or = 0.001) but not on DRT (P = 0.43). The use of neoadjuvant hormones had no significant effect on DRT (P = 0.64) or MRT (P = 0.76). The use of additional symptomatic medication during the study was not significantly different between the two arms. CONCLUSIONS: This study shows no significant difference in the urinary symptoms experienced during EBRT related to the consumption of cranberry juice compared with apple juice.
Abstract: Periodontitis is a chronic inflammatory disease affecting oral tissues. The continuous, high production of cytokines by host cells triggered by periodontopathogens is thought to be responsible for the destruction of tooth-supporting tissues. Macrophages play a critical role in this host inflammatory response to periodontopathogens. The aim of this study was to investigate the effect of non-dialyzable material prepared from cranberry juice concentrate on the pro-inflammatory cytokine response of macrophages induced by lipopolysaccharides (LPS) from Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum subsp. nucleatum, Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, and Escherichia coli. Interleukin-1 beta (IL-1beta), IL-6, IL-8, tumor necrosis factor alpha (TNF-alpha), and Regulated on Activation Normal T-cell Expressed and Secreted (RANTES) production by macrophages treated with the cranberry fraction prior to stimulation by LPS was evaluated by ELISA. Our results clearly indicate that the cranberry fraction was a potent inhibitor of the pro-inflammatory cytokine and chemokine responses induced by LPS. This suggests that cranberry constituents may offer perspectives for the development of a new therapeutic approach to the prevention and treatment of periodontitis.
Abstract: Cranberry juice consumption is often used for the treatment of urinary tract infections, but the effect of cranberry juice on heart disease has not been investigated. We evaluated how a cranberry extract containing 1,548 mg gallic acid equivalents/liter (initial pH=2.50) affected low density lipoprotein (LDL) oxidation induced by 10 micromolar cupric sulfate. When LDL oxidation took place in the presence of diluted cranberry extracts, the formation of thiobarbituric acid reactive substances (TBARS) and LDL electrophoretic mobility were reduced. LDL electrophoretic migration was also reduced when the cranberry extract had a pH of 7.00 prior to dilution. This study suggests that cranberry extracts have the ability to inhibit the oxidative modification of LDL particles.
Abstract: In urostomy patients, peristomal skin problems are common and may stem from alkaline urine. Cranberry juice appears to acidify urine and has bacteriostatic properties, and is widely recommended for the reduction of urinary tract infections. Therefore, it is hypothesized that drinking cranberry juice might also prevent and/or improve skin complications for urostomy patients. To test this hypothesis, pH measurements of the skin around the stoma and of the urine of 13 urostomy patients were taken before and after instituting a regimen of drinking 160 to 320 g of cranberry juice each day for an average period of six months. Results showed an improvement in skin condition from 6 patients with erythema, maceration or pseudoepithelial hyperplasia at the beginning of the study to 2 patients with maceration or PEH. The average pH of the urine taken from the patients' pouches decreased a statistically significant amount from 8.0 to 7.3 (p = 0.0277), yet unexpectantly, the average pH of the fresh urine increased a statistically significant amount from 5.8 to 6.2 (p = 0.0178). Other results were not statistically significant. The authors conclude that while drinking cranberry juice did not appear to acidify the urine as expected, improvements were still seen in the skin conditions of the study participants, suggesting that drinking cranberry juice does positively impact the incidence of skin complications for these patients.
Abstract: OBJECTIVES: Cranberry juice has been recommended for patients with recurrent urinary tract infections. However, cranberry juice has a moderately high concentration of oxalate, a common component of kidney stones, and should be limited in patients with a history of nephrolithiasis. Cranberry concentrate tablets are currently available at nutrition stores and are sold as promoters of urinary tract health. After one of our patients with a distant history of calcium oxalate nephrolithiasis developed recurrent stones following self-administration of cranberry concentrate tablets, we sought to investigate the potential lithogenic properties of cranberry supplements.
METHODS: Five healthy volunteers on a normal diet provided 24-hour urine collection for pH, volume, creatinine, oxalate, calcium, phosphate, uric acid, sodium, citrate, magnesium, and potassium. Cranberry tablets were administered to these volunteers at the manufacturer's recommended dosage for 7 days. On the seventh day, a second 24-hour urine collection was obtained.
RESULTS: The urinary oxalate levels in the volunteers significantly increased (P = 0.01) by an average of 43.4% while receiving cranberry tablets. The excretion of potential lithogenic ions calcium, phosphate, and sodium also increased. However, inhibitors of stone formation, magnesium and potassium, rose as well.
CONCLUSIONS: Cranberry concentrate tablets are marketed for urinary tract ailments. Physicians and manufacturers of cranberry products should make an effort to educate patients at risk for nephrolithiasis against ingestion of these dietary supplements.
Abstract: PURPOSE: We evaluated the effect of cranberry juice on urinary stone risk factors.
MATERIALS AND METHODS: A total of 12 normal subjects and 12 calcium oxalate stone formers underwent 2, 7-day phases of study in random order while on a controlled metabolic diet. Subjects ingested 1 l of cranberry juice (CBJ) daily in 1 phase and 1 l of deionized water in the other phase. On the last 2 days of each phase 2, 24-hour urine collections and blood samples were obtained for stone risk factors and serum chemistries.
RESULTS: No significant differences were found between normal subjects and stone formers in response to CBJ and, therefore, the groups were combined. CBJ significantly increased urinary calcium (from 154 to 177 mg per day, p =0.0008) and urinary oxalate (from 26.4 to 29.2 mg per day, p =0.04), thereby increasing urinary saturation of calcium oxalate by 18%. Urinary citrate was unchanged and urinary magnesium increased slightly. Urinary pH decreased (from 5.97 to 5.67, p =0.0005), and urinary ammonium, titratable acidity and net acid excretion increased during CBJ ingestion. Urinary uric acid decreased (from 544 to 442 mg per day, p <0.0001) as did serum uric acid. Thus, the urinary saturation of brushite and monosodium urate was reduced by CBJ but the amount of undissociated uric acid increased.
CONCLUSIONS: CBJ exerts a mixed effect on urinary stone forming propensity. It reduces urinary pH likely by providing an acid load and decreases urinary uric acid perhaps by retarding urate synthesis. Overall CBJ increases the risk of calcium oxalate and uric acid stone formation but decreases the risk of brushite stones.
Abstract: OBJECTIVE: To determine the effect of cranberry prophylaxis on rates of bacteriuria and symptomatic urinary tract infection in children with neurogenic bladder receiving clean intermittent catheterization.
DESIGN: Double-blind, placebo-controlled, crossover study of 15 children receiving cranberry concentrate or placebo concentrate for 6 months (3 months receiving one concentrate, followed by 3 months of the other). Weekly home visits were made. During each visit, a sample of bladder urine was obtained by intermittent catheterization. Signs and symptoms of urinary tract infection and all medications were recorded, and juice containers were counted.
RESULTS: During consumption of cranberry concentrate, the frequency of bacteriuria remained high. Cultures of 75% (114 of 151) of the 151 samples obtained during consumption of placebo were positive for a pathogen (>/=10(4) colony-forming units/mL) compared with 75% (120 of 160) of the 160 samples obtained during consumption of cranberry concentrate. Escherichia coli remained the most common pathogen during placebo and cranberry periods. Three symptomatic infections each occurred during the placebo and cranberry periods. No significant difference was observed in the acidification of urine in the placebo group versus the cranberry group (median, 5.5 and 6.0, respectively).
CONCLUSION: The frequency of bacteriuria in patients with neurogenic bladder receiving intermittent catheterization is 70%; cranberry concentrate had no effect on bacteriuria in this population.
Abstract: BACKGROUND: Porphyromonas gingivalis is a major aetiological agent of periodontitis, a destructive disease affecting the tooth-supporting tissues. Recent reports have indicated that high-molecular-weight molecules from cranberry juice concentrate can prevent the attachment of human pathogens to host tissues.
OBJECTIVES: The aim of the present study was to investigate the effect of non-dialysable material (NDM) prepared from cranberry juice concentrate on growth, biofilm formation and adherence properties of P. gingivalis.
METHODS: The effect of cranberry NDM on biofilm formation was studied using a polystyrene microplate assay and by scanning electron microscopy. The effect of cranberry NDM on the attachment properties of P. gingivalis was evaluated by a microplate assay in which mammalian proteins were immobilized into wells.
RESULTS: Our results indicated that cranberry NDM is a potent inhibitor of biofilm formation by P. gingivalis. However, it has no effect on growth and viability of bacteria. Cranberry NDM also prevented significantly the attachment of P. gingivalis to surfaces coated with type I collagen, fibrinogen or human serum.
CONCLUSIONS: Our data suggest that cranberry constituents may have a beneficial effect for the prevention and treatment of periodontitis by reducing the capacity of P. gingivalis to colonize periodontal sites.
Abstract: No abstract - The purpose of this study was to investigate the efficacy of carnberry juice and ascorbic acid in acidifying the urine of subjects with multiple sclerosis.
Abstract: Dental plaque stability depends on bacterial adhesion to acquired pellicle, and on interspecies adhesion (or coaggregation). A high-molecular-weight cranberry constituent at 0.6 to 2.5 milligrams per milliliter reversed the coaggregation of 49 (58 percent) of 84 coaggregating bacterial pairs tested. It acted preferentially on pairs in which one or both members are gram-negative anaerobes frequently involved in periodontal diseases. Thus, the anticoaggregating cranberry constituent has the potential for altering the subgingival microbiota, resulting in conservative control of gingival and periodontal diseases. However, the high dextrose and fructose content of the commercially available cranberry juice makes it unsuitable for oral hygiene use, and the beneficial effect of the high-molecular-weight constituent requires animal and clinical studies.
Abstract: A high-molecular-weight constituent of cranberry juice has been found to inhibit the sialyllactose specific adhesion of Helicobacter pylori strains to immobilized human mucus, erythrocytes, and cultured gastric epithelial cells. Different isolates of H. pylori differ in their affinity to the cranberry juice constituent. Cranberry juice may also inhibit adhesion of bacteria to the stomach in vivo, and may prove useful for the prevention of stomach ulcer that is caused by H. pylori.
Abstract: BACKGROUND AND OBJECTIVE: Periodontal diseases are a group of inflammatory disorders that are initiated by specific gram-negative bacteria and lead to connective tissue destruction. Proteolytic enzymes, including matrix metalloproteinases (MMPs) and elastase, produced by resident and inflammatory cells in response to periodontopathogens and their products, play a major role in gingival tissue destruction. The aim of this study was to investigate the effect of a high-molecular-weight fraction prepared from cranberry juice concentrate on MMP-3, MMP-9 and elastase activities, as well as on MMP production by human cells stimulated with lipopolysaccharide of Actinobacillus actinomycetemcomitans.
MATERIAL AND METHODS: MMP-3 and MMP-9 production by gingival fibroblasts and macrophages treated with the cranberry fraction and then stimulated with lipopolysaccharide was measured by enzyme-linked immunosorbent assay. MMP-3, MMP-9 and elastase activities in the presence of the cranberry fraction were evaluated using colorimetric or fluorogenic substrates. The changes in expression and phosphorylation state of fibroblast intracellular signaling proteins induced by A. actinomycetemcomitans lipopolysaccharide and the cranberry fraction were characterized by antibody microarrays.
RESULTS: The lipopolysaccharide-induced MMP-3 and MMP-9 responses of fibroblasts and macrophages were inhibited in a dose-dependent manner by the cranberry fraction. This fraction was found to inhibit fibroblast intracellular signaling proteins, a phenomenon that may lead to a down-regulation of activating protein-1 activity. MMP-3, MMP-9 and elastase activities were also efficiently inhibited by the cranberry fraction, even when it was used at low concentrations.
CONCLUSION: These results suggest that cranberry compounds offer promising perspectives for the development of novel host-modulating strategies for an adjunctive treatment of periodontitis.
Abstract: BACKGROUND: Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola are three major aetiological agents of chronic periodontitis. The strong proteolytic activities of these bacteria are critical to their survival since their energy source is obtained from peptides and amino acids derived from proteins. In addition, proteases are important factors contributing to periodontal tissue destruction by a variety of mechanisms, including direct tissue degradation and modulation of host inflammatory responses.
OBJECTIVES: The aim of this study was to investigate the effect of non-dialysable material (NDM) prepared from cranberry juice concentrate on the proteolytic activities of P. gingivalis, T. forsythia and T. denticola.
METHODS: The effect of NDM on gingipain and dipeptidyl peptidase IV (DPP IV) activities of P. gingivalis, trypsin-like activity of T. forsythia and chymotrypsin-like activity of T. denticola was evaluated using synthetic chromogenic peptides. In addition, the capacity of P. gingivalis to degrade fluorescein-labelled type I collagen and fluorescein-labelled transferrin in the presence of NDM was evaluated by fluorometry.
RESULTS: NDM dose-dependently inhibited the proteinases of P. gingivalis, T. forsythia and T. denticola as well as type I collagen and transferrin degradation by P. gingivalis.
CONCLUSIONS: These results suggest that NDM has the potential to reduce either the proliferation of P. gingivalis, T. forsythia and T. denticola in periodontal pockets or their proteinase-mediated destructive process occurring in periodontitis.
Abstract: Inhibition of bacterial adherence to bladder cells has been assumed to account for the beneficial action ascribed to cranberry juice and cranberry juice cocktail in the prevention of urinary tract infections (A. E. Sobota, J. Urol. 131:1013-1016, 1984). We have examined the effect of the cocktail and juice on the adherence of Escherichia coli expressing surface lectins of defined sugar specificity to yeasts, tissue culture cells, erythrocytes, and mouse peritoneal macrophages. Cranberry juice cocktail inhibited the adherence of urinary isolates expressing type 1 fimbriae (mannose specific) and P fimbriae [specific for alpha-D-Gal(1----4)-beta-D-Gal] but had no effect on a diarrheal isolate expressing a CFA/I adhesin. The cocktail also inhibited yeast agglutination by purified type 1 fimbriae. The inhibitory activity for type 1 fimbriated E. coli was dialyzable and could be ascribed to the fructose present in the cocktail; this sugar was about 1/10 as active as methyl alpha-D-mannoside in inhibiting the adherence of type 1 fimbriated bacteria. The inhibitory activity for the P fimbriated bacteria was nondialyzable and was detected only after preincubation of the bacteria with the cocktail. Cranberry juice, orange juice, and pineapple juice also inhibited adherence of type 1 fimbriated E. coli, most likely because of their fructose content. However, the two latter juices did not inhibit the P fimbriated bacteria. We conclude that cranberry juice contains at least two inhibitors of lectin-mediated adherence of uropathogens to eucaryotic cells. Further studies are required to establish whether these inhibitors play a role in vivo.
Abstract: INTRODUCTION: Cystitis is a bacterial infection of the lower urinary tract which causes pain when passing urine, and causes urgency, haematuria, and suprapubic pain not associated with passing urine. Recurrent cystitis is usually defined as three episodes of urinary tract infection in the previous 12 months, or two episodes in the previous 6 months. METHODS AND
OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: Which interventions prevent further recurrence of cystitis in women experiencing at least two infections per year? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS: We found 14 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: continuous antibiotic prophylaxis (trimethoprim, co-trimoxazole, nitrofurantoin, cefaclor, or a quinolone or cephalexin); continuous prophylaxis with methenamine hippurate; cranberry juice and cranberry products; oestrogen (topical) in postmenopausal women; passing urine after intercourse; postcoital antibiotic prophylaxis; single-dose self-administered antibiotic.
Abstract: Lower urinary tract symptoms (LUTS) are a common condition in older men. The objective of the present study was to evaluate the efficacy and tolerability of cranberry (Vaccinium macrocarpon) powder in men at risk of prostate disease with LUTS, elevated prostate-specific antigen (PSA), negative prostate biopsy and clinically confirmed chronic non-bacterial prostatitis. Forty-two participants received either 1500 mg of the dried powdered cranberries per d for 6 months (cranberry group; n 21) or no cranberry treatment (control group; n 21). Physical examination, International Prostate Symptom Score, quality of life (QoL), five-item version of the International Index of Erectile Function (IIEF-5), basic clinical chemistry parameters, haematology, Se, testosterone, PSA (free and total), C-reactive protein (CRP), antioxidant status, transrectal ultrasound prostate volume, urinary flow rate, ultrasound-estimated post-void residual urine volume at baseline, and at 3 and 6 months, and urine ex vivo anti-adherence activity were determined in all subjects. In contrast to the control group, patients in the cranberry group had statistically significant improvement in International Prostate Symptom Score, QoL, urination parameters including voiding parameters (rate of urine flow, average flow, total volume and post-void residual urine volume), and lower total PSA level on day 180 of the study. There was no influence on blood testosterone or serum CRP levels. There was no statistically significant improvement in the control group. The results of the present trial are the first firm evidence that cranberries may ameliorate LUTS, independent of benign prostatic hyperplasia or C-reactive protein level.
Abstract: OBJECTIVE: To evaluate the influence of plum-, cranberry- and blackcurrant juice on urinary stone risk factors.
DESIGN: Investigations were carried out in 12 healthy male subjects aged 18-38 y. All subjects received a standardized diet formulated according to the dietary recommendations of the German Society of Nutrition. The subjects provided 24 h urine collections in a control, three loading phases. In each loading phase a neutral mineral water was substituted for 330 ml of the particular juice.
RESULTS: Cranberry juice decreased the urinary pH, whereas the excretion of oxalic acid and the relative supersaturation for uric acid were increased. Blackcurrant juice increased the urinary pH and the excretion of citric acid. The excretion of oxalic acid was increased too. All changes were statistically significant. The plum juice had no significant effect on the urinary composition.
CONCLUSION: It is concluded that blackcurrant juice could support the treatment and metaphylaxis of uric acid stone disease because of its alkalizing effect. Since cranberry juice acidifies urine it could be useful in the treatment of brushite and struvite stones as well as urinary tract infection.
Abstract: Clinical, epidemiological and mechanistic studies support the role of cranberry (Vaccinium macrocarpon Ait.) in maintaining urinary tract health. Cranberry proanthocyanidins contain A-type linkages and have been associated with preventing adhesion of P-fimbriated uropathogenic Escherichia coli to uroepithelial cells. It is not known if the presence of the A-type linkage is a prerequisite for anti-adhesion activity. Other commercial sources of proanthocyanidins with all B-type linkages have not previously been screened for this activity. The goals of this study were to compare the in vitro anti-adhesion activity of A-linked proanthocyanidins from cranberry juice cocktail with the anti-adhesion activities of B-linked proanthocyanidins from commercial grape and apple juices, green tea and dark chocolate, and determine if anti-adhesion activity is detectable in human urine following consumption of single servings of each commercial food product. Structural heterogeneity and presence of the A-type linkage in cranberry proanthocyanidins was confirmed utilizing MALDI-TOF/MS and DI/ESI MS, as was the presence of all B-type linkages in the proanthocyanidins from the other commercial products. The isolated A-type proanthocyanidins from cranberry juice cocktail elicited in vitro anti-adhesion activity at 60 microg/ml, the B-type proanthocyanidins from grape exhibited minor activity at 1200 microg/ml, while other B-type proanthocyanidins were not active. Anti-adhesion activity in human urine was detected following cranberry juice cocktail consumption, but not after consumption of the non-cranberry food products. Results suggest that presence of the A-type linkage in cranberry proanthocyanidins may enhance both in vitro and urinary bacterial anti-adhesion activities and aid in maintaining urinary tract health.
Abstract: No abstract - Introduction: It is well “known” by the general lay public that cranberry juice is helpful in treating and preventing urinary tract infections (UTIs). However, the evidence for this assumption has never been critically reviewed in urologic reports or elsewhere. The evidence for the two proposed mechanisms of action of cranberry juice, urinary acidification and inhibition of bacterial adherence, are critically analyzed.
Abstract: OBJECTIVE: This study compares the effects of daily cranberry juice to those of Lactobacillus in children with recurrent urinary tract infections (UTIs).
MATERIAL AND METHODS: Eighty-four girls aged between 3 and 14 years were randomized to cranberry, Lactobacillus or control in three treatment arms: G1, cranberry juice 50 ml daily (n=28); G2, 100 ml of Lactobacillus GG drink on 5 days a month (n=27); and G3, controls (n=29). The study lasted for 6 months.
RESULTS: Only four subjects withdrew: 1/28 (3.5%) from G1, 1/27 (3.7%) from G2 and 2/29 (6.8%) from G3, because of poor compliance to the established protocol. There were 34 episodes of UTIs in this cohort: 5/27 (18.5%) in G1, 11/26 (42.3%) in G2 and 18/27 (48.1%) in the G3, with at least one episode of infection (p<0.05).
CONCLUSION: These data suggest that daily consumption of concentrated cranberry juice can significantly prevent the recurrence of symptomatic UTIs in children.
Abstract: PURPOSE: Cranberry proanthocyanidins have been identified as possible inhibitors of Escherichia coli adherence to uroepithelial cells. However, little is known about the dose range of this effect. Furthermore, it has not been studied directly in the urogenital system. To address these issues we tested the effect of a cranberry powder and proanthocyanidin extract on adherence of a P-fimbriated uropathogenic E. coli isolate to 2 new urogenital model systems, namely primary cultured bladder epithelial cells and vaginal epithelial cells.
MATERIALS AND METHODS: E. coli IA2 was pre-incubated with a commercially available cranberry powder (9 mg proanthocyanidin per gm) or with increasing concentrations of proanthocyanidin extract. Adherence of E. coli IA2 to primary cultured bladder epithelial cells or vaginal epithelial cells was measured before and after exposure to these products.
RESULTS: Cranberry powder decreased mean adherence of E. coli IA2 to vaginal epithelial cells from 18.6 to 1.8 bacteria per cell (p <0.001). Mean adherence of E. coli to primary cultured bladder epithelial cells was decreased by exposure to 50 mug/ml proanthocyanidin extract from 6.9 to 1.6 bacteria per cell (p <0.001). Inhibition of adherence of E. coli by proanthocyanidin extract occurred in linear, dose dependent fashion over a proanthocyanidin concentration range of 75 to 5 mug/ml.
CONCLUSIONS: Cranberry products can inhibit E. coli adherence to biologically relevant model systems of primary cultured bladder and vaginal epithelial cells. This effect occurs in a dose dependent relationship. These findings provide further mechanistic evidence and biological plausibility for the role of cranberry products for preventing urinary tract infection.
Abstract: PURPOSE: We compared the effects of daily cranberry juice cocktail to those of placebo during pregnancy on asymptomatic bacteriuria and symptomatic urinary tract infections.MATERIALS AND METHODS: A total of 188 women were randomized to cranberry or placebo in 3 treatment arms of A-cranberry 3 times daily (58), B-cranberry at breakfast then placebo at lunch and dinner (67), and C-placebo 3 times daily (63). After 27.7% (52 of 188) of the subjects were enrolled in the study the dosing regimens were changed to twice daily dosing to improve compliance.RESULTS: There were 27 urinary tract infections in 18 subjects in this cohort, with 6 in 4 group A subjects, 10 in 7 group B subjects and 11 in 7 group C subjects (p = 0.71). There was a 57% and 41% reduction in the frequency of asymptomatic bacteriuria and all urinary tract infections, respectively, in the multiple daily dosing group. However, this study was not sufficiently powered at the alpha 0.05 level (CI 0.14-1.39 and 0.22-1.60, respectively, incidence rate ratios). Of 188 subjects 73 (38.8%) withdrew, most for gastrointestinal upset.CONCLUSIONS: These data suggest there may be a protective effect of cranberry ingestion against asymptomatic bacteriuria and symptomatic urinary tract infections in pregnancy. Further studies are planned to evaluate this effect.
Abstract: OBJECTIVE: To test the recommendation that to avoid the complications of long-term indwelling bladder catheterization (e.g. encrustation and blockage by crystalline Proteus mirabilis biofilms) patients should drink cranberry juice. MATERIALS AND METHODS: Urine was collected from groups of volunteers who had drunk up to 2 x 500 mL of cranberry juice or water within an 8-h period. Laboratory models of the catheterized bladder were supplied with urine from these groups and inoculated with P. mirabilis. After incubation for 24 or 48 h, the extent of catheter encrustation was determined by chemical analysis for calcium and magnesium. Encrustation was also visualized by scanning electron microscopy. RESULTS: The amounts of calcium and magnesium recovered from catheters incubated in urine pooled from individuals who had drunk 500 mL of cranberry juice was not significantly different from that on catheters incubated in pooled urine from control subjects who had drunk 500 mL of water. However, there was significantly less encrustation (P = 0.007) on catheters from models receiving urine from volunteers who had drunk 2 x 500 mL of water than on catheters incubated in models supplied with urine from volunteers who had drunk 2 x 500 mL of cranberry juice. The amounts of encrustation on these two groups of catheters were also significantly less than that on catheters incubated in models supplied with urine from volunteers who had not supplemented their normal fluid intake. (P < 0.001). Experiments in the models using artificial urine showed that increasing the low fluid intake (720 mL/24 h) characteristic of many patients undergoing long-term catheterization by factors of three and six, significantly (P < 0.01) reduced the amounts of calcium and magnesium that formed on catheters. At a simulated fluid intake of 720 mL/24 h, catheters blocked with encrustation after a mean of 42.5 h, while those supplied with urine produced from an intake of 4320 mL/24 h, drained freely for > 10 days. CONCLUSION: In this in vitro study, drinking cranberry juice did not produce urine that was inhibitory to the development of crystalline catheter-blocking P. mirabilis biofilms. The important factor in preventing catheter encrustation is a high fluid intake.
Abstract: INTRODUCTION/OBJECTIVE: Cranberries have been shown to produce urinary metabolites that influence uropathogen adhesion and prevent urinary tract infections. This study was designed to determine if consuming reconstituted, unsweetened cranberry drink from extract retained its bioactive properties by reducing uropathogen adhesion without adversely affecting urinary calcium, magnesium and the vaginal microflora. MATERIALS AND METHODS: A randomized crossover study was undertaken in 12 healthy women consuming reconstituted unsweetened cranberry drink, CranActin or water. The urine was collected at 4 hours and 1 week of consumption and evaluated for antiadhesive properties and urinary pH, calcium and magnesium. Vaginal swabs were collected after 1 week of treatment to assess the vaginal microbiota by DGGE. RESULTS: The resultant urine produced by subjects who consumed 500 ml reconstituted cranberry extract twice per day, significantly reduced the adherence to epithelial cells of P-fimbriated uropathogenic Escherichia coli and showed a tendency towards significance for two E. coli strains expressing fimbriae and an Enterococcus faecalis isolate. The cranberry drink treatment did not alter urinary pH, but reduced calcium and magnesium concentrations compared to water, although not to statistical significance. The reconstituted cranberry drink had no apparent detrimental effect on the vaginal microbiota. However, consuming twice daily resulted in an apparent loss of a potential pathogen from the vagina in 42% subjects. CONCLUSIONS: The present findings suggest that reconstituted cranberry drink may retain the ability to reduce the risk of UTI by inhibiting pathogen adhesion while not detrimentally affecting urinary pH or vaginal microbiota, or the risk of calculi
Abstract: Cranberry constituents are known to exert anti-adhesion activity on H. pylori in vitro. To determine their possible additive effect to triple therapy with omeprazole, amoxicillin and clarithromycin (OAC), a double-blind randomized clinical study was carried out. One-hundred-seventy-seven patients with H. pylori infection treated with OAC for 1 week were randomly allocated to receive 250 mL of either cranberry juice (cranberry-OAC, n = 89) or placebo beverage (placebo-OAC, n = 88) twice daily and only cranberry juice or placebo beverage for the next 2 weeks. Treatment outcome was determined with the(13)C urea breath test ((13)C-UBT). An additional control group consisted of patients referred to the same center during the same period who were treated with OAC alone for 1 week (non-placebo-OAC, n = 712). Overall, the rate of H. pylori eradication ((13)C-UBT < 3.5) was 82.5%, with no statistically significant difference among the three arms. Analysis by gender revealed that for female subjects, the eradication rate was higher in the cranberry-OAC arm (n = 42, 95.2%) than in the placebo-OAC arm (n = 53, 86.8%) and significantly higher than in the non-placebo-OAC group (n = 425, 80%; p = 0.03). For males, the rate was nonsignificantly lower in the cranberry-OAC arm (n = 35, 73.9%) than in the placebo-OAC arm (n = 45, 80.0%) and non-placebo-OAC group (n = 287, 85.0%). These results suggest that the addition of cranberry to triple therapy improves the rate of H. pylori eradication in females.
Abstract: An experimental study was conducted on 3 consecutive 12-hour days to determine if selected physical properties of feeding tubes (material and diameter) affect tube clogging. Effectiveness of three irrigant fluids (cranberry juice, Coca-Cola, and water) in preventing tube clogging was studied. One hundred eight tubes were connected to gravity flow feeding bags containing isotonic enteral formula; 54 polyurethane and 54 silicone tubes were equally divided as to external diameters of 8 French (Fr), 10 Fr, and 12 Fr. At 4-hour intervals, flow regulators on the feeding bags were adjusted to a rate of 50 ml/hour. Fluid volumes delivered per minute were measured for each tube at 2-hour intervals. One set of tubes at each station was irrigated periodically with cranberry juice, Coca-Cola, or water. On each of the 3 days, analyses revealed significant, p less than .05, effects for tube material, cranberry juice contrasted with Coca-Cola and water as irrigants, and time. Polyurethane was consistently superior to silicone as a tube material, and cranberry juice was consistently inferior to both Coca-Cola and water as an irrigant. Tube diameter had no significant effect on the incidence of tube clogging.
Abstract: No abstract
Abstract: "AIMS: To investigate the influence of several phenolic compounds isolated from cranberry fruit (Vaccinium macrocarpon) on some of the virulence properties of Streptococcus mutans associated with glucan synthesis and acidogenicity.
METHODS AND RESULTS: Individual phenolic acids, flavonols and proanthocyanidins were isolated by semi-preparative high-performance liquid chromatography from fresh cranberry fruit. Flavonols and proanthocyanidins (at 500 micromol l(-1)) moderately inhibited the activity of surface-adsorbed glucosyltransferases (GTFs) B and C and F-ATPases (15-35% inhibition; P < 0.05), and also disrupted acid production by S. mutans cells without affecting bacterial viability. Phenolic acids displayed minimal biological effects. Quercetin-3-arabinofuranoside, myricetin and procyanidin A2 displayed the most inhibition of S. mutans virulence traits; a combination of these compounds displayed enhanced effects.
CONCLUSIONS: Specific flavonoids from cranberries exhibit statistically significant but moderate biological activity against S. mutans. The biological activity of cranberry extracts may be a result from the complex mixture of flavonoids rather than a single active compound.
SIGNIFICANCE AND IMPACT OF STUDY: This is the first study to identify the bioactive constituents in cranberry against an oral bacterium using highly purified isolated compounds. The combined effects of specific flavonols and proanthocyanidins from cranberry on GTFs activity, acid production and acid tolerance of S. mutans make them attractive compounds to fully explore for their anti-biofilm and cariostatic properties."
Abstract: Cranberry juice has been widely used for the treatment and prevention of urinary tract infections and is reputed to give symptomatic relief from these infections. Attempts to account for the potential benefit derived from the juice have focused on urine acidification and bacteriostasis. In this investigation it is demonstrated that cranberry juice is a potent inhibitor of bacterial adherence. A total of 77 clinical isolates of Escherichia coli were tested. Cranberry juice inhibited adherence by 75 per cent or more in over 60 per cent of the clinical isolates. Cranberry cocktail was also given to mice in the place of their normal water supply for a period of 14 days. Urine collected from these mice inhibited adherence of E. coli to uroepithelial cells by approximately 80 per cent. Antiadherence activity could also be detected in human urine. Fifteen of 22 subjects showed significant antiadherence activity in the urine 1 to 3 hours after drinking 15 ounces of cranberry cocktail. It is concluded that the reported benefits derived from the use of cranberry juice may be related to its ability to inhibit bacterial adherence.
Abstract: Strains of uropathogenic E. coli are responsible for approximately 90% of community-acquired, uncomplicated cystitis, and fimbriae represent the adhesive factors enabling E. coli to be anchored to uroepithelial cells in the first step of the infectious process. Recently, a few studies have shown that a correlation between the consumption of cranberry (Vaccinium macrocarpon) and prevention of UTI is related to the ability of proanthocyanidins to reduce the bacterial adhesion to uroepithelial cells. In this study we evaluate the inhibitory activity of urine of healthy women treated with tablets containing cranberry extract on the adhesiveness of E. coli to uroepithelial human cells. Two groups of 12 female volunteers each, aged between 18 and 65 years, were enrolled, one group with negative history and one group with positive history of recurrent cystitis. Subjects were treated with the active product or placebo in a random, cross-over, double-blinded sequence for one week in each of the two treatment sequences. Urine samples were collected at the beginning and the end of each study period. Tests of bacterial adhesiveness were performed with two strains of E. coli (ATCC 25922 and ATCC 35218) on HT1376 human bladder carcinoma cells. Significant reductions of bacterial adhesiveness were observed in women who received cranberry extract (-50.9%; p less than 0.0001), regardless of their medical history and the treatment period in the cross-over sequence. No changes were observed with placebo (-0.29%; n.s.). This ex-vivo study showed that the assumption of cranberry extract in suitable amounts can have an anti-adhesive activity on uropathogenic E. coli.
Abstract: The ability of Vaccinum macrocarpon, the North American cranberry, to prevent bacterial adhesion has been used to advantage in the prevention of urinary tract infections and has recently been described for the prevention of adhesion of bacteria responsible for oral infections and stomach ulcers. This report documents the ability of cranberry juice to reduce nonspecific adhesion of bacteria to the borosilicate glass microscope slides used in an immunoarray biosensor format. Nonspecific binding of analytes in the array sensor leads to high background signals that cause increased detection limits and false positives. Reduction in background-to-signal ratios can be seen as the juice concentration is increased from 0 to 50% of the sample. This impact cannot be duplicated with grape, orange, apple, or white cranberry juice. Sugar content and pH have been eliminated as the agents in the juice responsible for the anti-adhesive activity.
Abstract: OBJECTIVE: To evaluate the protective effects of cranberry fruit, which have known antioxidant effects, on infection-induced oxidative renal damage in a rabbit model of vesico-ureteric reflux (VUR). MATERIALS AND METHODS: In all, 36 New Zealand male rabbits were divided into five groups, with a sham operation in four rabbits serving as the control (group 1). To create unilateral VUR the roof of the left intravesical ureter was incised, and VUR confirmed 2 weeks after surgery. In all, 32 rabbits with VUR were divided into four groups; 2, VUR alone (with sterile urine); 3, a group infected with Escherichia coli; 4, with intravesical E. coli instillation but fed cranberries; and 5, intravesical E. coli instillation plus an intraperitoneal injection with melatonin group. At 3 weeks after surgery the rabbits were killed, the kidneys obtained and examined histopathologically to evaluate inflammation, fibrosis and tubular changes. Oxidative renal damage was evaluated by measuring malondialdehyde in the renal tissue. RESULTS: Grossly, the refluxing kidney was larger than the contralateral normal kidney, and the refluxing ureter was dilated and tortuous. Microscopy of tissues from the kidneys in group 3 showed apparent periglomerular mononuclear cell infiltration, tubular dilatation and atrophy, and interstitial fibrosis. The kidneys from groups 2, 4 and 5 showed mild mononuclear cell infiltration with no interstitial fibrosis. The level of malondialdehyde in the kidneys of group 3 was significantly higher than that in group 2, 4 and 5 (P < 0.05); the level in groups 4 and 5 did not differ significantly from that in group 2. CONCLUSIONS: This study shows that cranberries have an anti-inflammatory effect through their antioxidant function and might prevent infection-induced oxidative renal damage. Thus, clinically cranberries might be used as a beneficial adjuvant treatment to prevent damage due to pyelonephritis in children with VUR.
Abstract: OBJECTIVE: To determine the effect of regular intake of cranberry juice beverage on bacteriuria and pyuria in elderly women.
DESIGN: Randomized, double-blind, placebo-controlled trial.
SUBJECTS: Volunteer sample of 153 elderly women (mean age, 78.5 years).
INTERVENTION: Subjects were randomly assigned to consume 300 mL per day of a commercially available standard cranberry beverage or a specially prepared synthetic placebo drink that was indistinguishable in taste, appearance, and vitamin C content but lacked cranberry content.
OUTCOME MEASURES: A baseline urine sample and six clean-voided study urine samples were collected at approximately 1-month intervals and tested quantitatively for bacteriuria and the presence of white blood cells.
RESULTS: Subjects randomized to the cranberry beverage had odds of bacteriuria (defined as organisms numbering > or = 10(5)/mL) with pyuria that were only 42% of the odds in the control group (P = .004). Their odds of remaining bacteriuric-pyuric, given that they were bacteriuric-pyuric in the previous month, were only 27% of the odds in the control group (P = .006).
CONCLUSIONS: These findings suggest that use of a cranberry beverage reduces the frequency of bacteriuria with pyuria in older women. Prevalent beliefs about the effects of cranberry juice on the urinary tract may have microbiologic justification.
Abstract: BACKGROUND: There is a lack of basic knowledge on the part of both clinicians and patients as to the indications for use and safety of herbs used during pregnancy and lactation. This is one article in a series that systematically reviews the evidence for herbs commonly used during pregnancy and lactation. OBJECTIVES: To systematically review the literature for evidence on the use, safety and pharmacology of cranberry, focusing on issues pertaining to pregnancy and lactation. METHODS: We searched 7 electronic databases and compiled data according to the grade of evidence found. RESULTS: There is no direct evidence of safety or harm to the mother or fetus as a result of consuming cranberry during pregnancy. Indirectly, there is good scientific evidence that cranberry may be of minimal risk, where a survey of 400 pregnant women did not uncover any adverse events when cranberry was regularly consumed. In lactation, the safety or harm of cranberry is unknown. CONCLUSIONS: Women experience urinary tract infections with greater frequency during pregnancy. Given the evidence to support the use of cranberry for urinary tract infections (UTIs) and its safety profile, cranberry supplementation as fruit or fruit juice may be a valuable therapeutic choice in the treatment of UTIs during pregnancy.
Abstract: Abstract: Urinary ionized calcium was determined by a calcium activity electrode in 32 normal persons and in 54 patients with calcium-containing renal stones and without urinary tract infection. It was found to be 38 per cent higher in patients with calcium-containing renal stone in comparison to normal persons. However, this was not statistically significant. No consistant change in total or ionized calcium excretion was produced in normal volunteers by the administration of as much as 5 pints of cranberry juice. In patients with renal stones, the urinary ionized calcium was reduced during the cranberry juice ingestion by 50 per cent, which was statistically highly significant.
Abstract: PURPOSE: This review provides practicing urologists with important basic information about urinary tract infections (UTIs) that can be applied to everyday clinical problems.
MATERIALS AND METHODS: A review is presented of provocative and controversial concepts in the current literature.
RESULTS: Bacterial virulence mechanisms are critical for overcoming the normal host defenses. Increasing antimicrobial resistance of uropathogens has led to reconsideration of traditional treatment recommendations in many areas. For effective patient management the first issue is to define complicating urological factors. Managing complicated urinary tract infections, particularly in urology, is determined by clinical experience to define the pertinent anatomy and to determine the optimal interventions. New clinical data are summarized on UTIs in long-term care patients, behavioral risks for UTI in healthy women and anatomical differences associated with an increased risk for UTI. The rationale is presented for UTI prophylaxis using cranberry juice, immunization and bacterial interference. Current treatment trends for UTI include empiric therapy (without urine culture and sensitivity testing), short-course therapy, patient-administered (self-start) therapy and outpatient therapy for uncomplicated pyelonephritis.
CONCLUSIONS: Recommendations for treating patients with UTIs have changed based on basic science and clinical experience.
Abstract: In this review we assess the effectiveness of cranberry and blueberry products in preventing symptomatic urinary tract infections (UTIs). Selection criteria were randomised or quasi-randomised controlled trials of cranberry or blueberry juice/products for the prevention of symptomatic UTIs. A comprehensive search was undertaken in November 2006 whereupon two reviewers independently assessed and extracted data. Quality was assessed using Cochrane criteria. Relative risks (RR) were calculated where appropriate; otherwise a narrative synthesis was undertaken. No relevant trials of blueberry products were identified. Nine trials of cranberry products met the inclusion criteria. In four good quality randomised controlled trials (RCTs), cranberry products significantly reduced the incidence of symptomatic UTIs in 12 months (overall RR 0.65, 95% CI: 0.46-0.90) compared with placebo/control. Five trials were not included in the meta-analyses due to the lack of appropriate data. However, only one reported a significant result. Side effects were common, and losses to followup/withdrawals in several of the trials were high (> 40%). There is some evidence from four good quality RCTs that cranberry juice may decrease the number of symptomatic UTIs over a 12-month period, particularly in women with recurrent UTIs. It is uncertain whether it is effective in other susceptible groups.
Abstract: Studies were undertaken to investigate the antiviral effects of comestible juices, especially cranberry juice, on non-related viral species. After exposure of bacteriophage T2 to a commercially available cranberry (Vaccinium macrocarpon) juice cocktail (CJ), virus infectivity titer was no longer detectible. After a 60-min exposure to orange (OJ) and grapefruit juices (GJ), phage infectivity was reduced to 25-35% of control, respectively. Similar data were observed for the bacteriophage T4. CJ inactivation of phage T4 was rapid, dose-dependent, and occurred at either 4 or 23 degrees C. Neither pH nor differences in sugar/carbohydrate levels among the juices may be ascribed to the recognized antiviral effects. Further studies were performed to identify the occurrence of antiviral activity by CJ to a mammalian enteric virus. The treatment of the simian rotavirus SA-11 with a 20% CJ suspension was sufficient to inhibit hemagglutination. Under scanning and transmission electron microscopy, CJ was observed to inhibit the adsorption of phage T4 to its bacterial host cells and prevented the replication of rotavirus in its monkey kidney (MA-104) host cells, respectively. The data suggest, for the first time, a non-specific antiviral effect towards unrelated viral species (viz., bacteriophages T2 and T4 and the simian rotavirus SA-11) by a commercially available cranberry fruit juice drink.
Abstract: Cranberry (Vaccinium macrocarpon Ait.) ingestion has long been associated with prevention of urinary tract infections. The beneficial mechanism was historically thought to be due to the fruit acids causing a bacteriostatic effect in the urine. However, recently, a group of proanthocyanidins (PACs) with A-type linkages were isolated from cranberry which exhibit bacterial antiadhesion activity against both antibiotic susceptible and resistant strains of uropathogenic P-fimbriated Escherichia coli bacteria. The link between cranberry ingestion and maintenance of urinary tract health as well as the structural diversity, pharmacokinetics, quantification, and bacterial antiadhesion bioactivity of the A-linked cranberry PACs are reviewed.
Abstract: The anti-adhesive effects of cranberry have been attributed to both interactions of its components with the surface of bacterial cells and to inhibition of p-fimbriae expression. Previous reports also suggested that the presence of cranberry juice changed the Gram stain characteristics of Escherichia coli. Here, we show that the morphology of E. coli is changed when grown in the presence of juice or extract from Vaccinium macrocarpon (cranberry). Gene expression analysis indicates the down regulation of flagellar basal body rod and motor proteins. Consistent with this finding and previous reports, the SEM images indicate a decrease in the visible p-fimbriae. The iodine used in Gram-staining protocols was found to interact differently with the bacterial membrane when cells were cultured in spiked media. Slight alterations in the Gram stain protocol demonstrated that culturing in the presence of cranberry juice does not change the Gram stain characteristics contradicting other reports.
Abstract: This study evaluated the antibacterial efficacy of the consumption of cranberry capsules vs. placebo in the urine of healthy volunteers. A first double-blind, randomised, crossover trial involved eight volunteers who had followed three regimens, with or without cranberry, with a wash-out period of at least 6 days between each regimen. Twelve hours after consumption of cranberry or placebo hard capsules, the first urine of the morning was collected. Different Escherichia coli strains were cultured in the urine samples. Urinary antibacterial adhesion activity was measured in vitro using the human T24 epithelial cell-line, and in vivo using the Caenorhabditis elegans killing model. With the in-vitro model, 108 mg of cranberry induced a significant reduction in bacterial adherence to T24 cells as compared with placebo (p <0.001). A significant dose-dependent decrease in bacterial adherence in vitro was noted after the consumption of 108 and 36 mg of cranberry (p <0.001). The in-vivo model confirmed that E. coli strains had a reduced ability to kill C. elegans after growth in the urine of patients who consumed cranberry capsules. Overall, these in-vivo and in-vitro studies suggested that consumption of cranberry juice represents an interesting new strategy to prevent recurrent urinary tract infection.
Abstract: OBJECTIVE: To determine whether Methenamine Hippurate (MH) or cranberry tablets prevent urinary tract infections (UTI) in people with neuropathic bladder following spinal cord injury (SCI).
STUDY DESIGN: Double-blind factorial-design randomized controlled trial (RCT) with 2 year recruitment period from November 2000 and 6 month follow-up.
SETTING: In total, 543 eligible predominantly community dwelling patients were invited to participate in the study, of whom 305 (56%) agreed.
METHODS: Eligible participants were people with SCI with neurogenic bladder and stable bladder management. All regimens were indistinguishable in appearance and taste. The dose of MH used was 1 g twice-daily. The dose of cranberry used was 800 mg twice-daily. The main outcome measure was the time to occurrence of a symptomatic UTI.
RESULTS: Multivariate analysis revealed that patients randomized to MH did not have a significantly longer UTI-free period compared to placebo (HR 0.96, 95% CI: 0.68-1.35, P=0.75). Patients randomized to cranberry likewise did not have significantly longer UTI-free period compared to placebo (HR 0.93, 95% CI: 0.67-1.31, P=0.70).
CONCLUSION: There is no benefit in the prevention of UTI from the addition of MH or cranberry tablets to the usual regimen of patients with neuropathic bladder following SCI.
Abstract: PURPOSE: To determine, from a societal perspective, the effectiveness and cost effectiveness of concentrated cranberry tablets, versus cranberry juice, versus placebo used as prophylaxis against lower urinary tract infection (UTI) in adult women.MATERIALS AND METHODS: One hundred fifty sexually active women aged 21 through 72 years were randomized for one year to one of three groups of prophylaxis: placebo juice + placebo tablets versus placebo juice + cranberry tablets, versus cranberry juice + placebo tablets. Tablets were taken twice daily, juice 250 ml three times daily. Outcome measures were: (1) a >50% decrease in symptomatic UTI's per year (symptoms + >or= 100 000 single organisms/ml) and (2) a >50% decrease in annual antibiotic consumption. Cost effectiveness was calculated as dollar cost per urinary tract infection prevented. Stochastic tree decision analytic modeling was used to identify specific clinical scenarios for cost savings.RESULTS: Both cranberry juice and cranberry tablets statistically significantly decreased the number of patients experiencing at least 1 symptomatic UTI/year (to 20% and 18% respectively) compared with placebo (to 32%) (p<0.05). The mean annual cost of prophylaxis was $624 and $1400 for cranberry tablets and juice respectively. Cost savings were greatest when patients experienced >2 symptomatic UTI's per year (assuming 3 days antibiotic coverage) and had >2 days of missed work or required protective undergarments for urgency incontinence. Total antibiotic consumption was less annually in both treatment groups compared with placebo. Cost effectiveness ratios demonstrated cranberry tablets were twice as cost effective as organic juice for prevention.CONCLUSIONS: Cranberry tablets provided the most cost-effective prevention for UTI.
Abstract: In a previous investigation it was demonstrated that cranberry juice cocktail was able to inhibit adherence in 77 clinical isolates of Escherichia coli obtained from patients with diagnosed urinary tract infections. This work has been extended to include clinical isolates of E. coli, Proteus, Klebsiella, Enterobacter and Pseudomonas isolated from urine, sputum, wound and stool. Bacterial strains isolated from urine adhere in greater numbers to urinary tract epithelial cells than organisms isolated from sputum, stool and wound sources. E. coli, isolated from urine, adheres to urinary epithelial cells, in numbers three times greater than E. coli isolated from other clinical sources, and thus appears to represent a unique population of cells in terms of adherence. Cranberry juice cocktail and urine and urinary epithelial cells obtained after drinking the cocktail all demonstrate antiadherence activity against Gram-negative rods isolated from urine and other clinical sources. Drinking the cocktail may be useful in managing urinary tract infections in certain patients.
Abstract: Cranberries have been suggested to decrease the attachment of bacteria to uroepithelial cells (UC), thus preventing urinary tract infections, although the mechanisms are not well understood. A thermodynamic approach was used to calculate the Gibbs free energy of adhesion changes (DeltaG(adh)) for bacteria-UC interactions, based on measuring contact angles with three probe liquids. Interfacial tensions and DeltaG(adh) values were calculated for Escherichia coli HB101pDC1 (P-fimbriated) and HB101 (non-fimbriated) exposed to cranberry juice (0-27 wt.%). HB101pDC1 can form strong bonds with the Gal-Gal disaccharide receptor on uroepithelial cells, while HB101-UC interactions are only non-specific. For HB101 interacting with UC, DeltaG(adh) was always negative, suggesting favorable adhesion, and the values were insensitive to cranberry juice concentration. For the HB101pDC1-UC system, DeltaG(adh) became positive at 27wt.% cranberry juice, suggesting that adhesion was unfavorable. Acid-base (AB) interactions dominated the interfacial tensions, compared to Lifshitz-van der Waals (LW) interactions. Exposure to cranberry juice increased the AB component of the interfacial tension of HB101pDC1. LW interactions were small and insensitive to cranberry juice concentration. The number of bacteria attached to UC was quantified in batch adhesion assays and quantitatively correlated with DeltaG(adh). Since the thermodynamic approach should not agree with the experimental results when specific interactions are present, such as HB101pDC-UC ligand-receptor bonds, our results may suggest that cranberry juice disrupts bacterial ligand-UC receptor binding. These results help form the mechanistic explanation of how cranberry products can be used to prevent bacterial attachment to host tissue, and may lead to the development of better therapies based on natural products.
Abstract: Traditionally, cranberry has been used for the treatment and prophylaxis of urinary tract infections. Research suggests that its mechanism of action is preventing bacterial adherence to host cell surface membranes. Systematic reviews have concluded that no reliable evidence supports the use of cranberry in the treatment or prophylaxis of urinary tract infections; however, more recent, randomized controlled trials demonstrate evidence of cranberry's utility in urinary tract infection prophylaxis. Supporting studies in humans are lacking for other clinical uses of cranberry. Cranberry is a safe, well-tolerated herbal supplement that does not have significant drug interactions.
Abstract: Scope: Atomic force microscopy (AFM) was used to directly measure the nanoscale adhesion forces between P-fimbriated Escherichia coli (E. coli) and human uroepithelial cells exposed to cranberry juice, in order to reveal the molecular mechanisms by which cranberry juice cocktail (CJC) affects bacterial adhesion.Methods and results: Bacterial cell probes were created by attaching P-fimbriated E. coli HB101pDC1 or non-fimbriated E. coli HB101 to AFM tips, and the cellular probes were used to directly measure the adhesion forces between E. coli and uroepithelial cells in solutions containing: 0, 2.5, 5, 10, and 27 wt% CJC. Macroscale attachment of E. coli to uroepithelial cells was measured and correlated to nanoscale adhesion force measurements. The adhesion forces between E. coli HB101pDC1 and uroepithelial cells were dose-dependent, and decreased from 9.32+/-2.37 nN in the absence of CJC to 0.75+/-0.19 nN in 27 wt% CJC. Adhesion forces between E. coli HB101 and uroepithelial cells were low in buffer (0.74+/-0.18 nN), and did not change significantly in CJC (0.78+/-0.18 nN in 27 wt% CJC; P=0.794).Conclusion: Our study shows that CJC significantly decreases nanoscale adhesion forces between P-fimbriated E. coli and uroepithelial cells.
Abstract: The chemopreventive efficacy of cranberry juice concentrate in an experimental model of urinary bladder cancer was evaluated using female Fischer-344 rats. The animals received N-butyl-N-(4-hydroxybutyl)-nitrosamine (OH-BBN) for a period of eight weeks. Cranberry juice concentrate was administered at doses of 1.0 or 0.5 ml/rat/day beginning one week after the final OH-BBN treatment and continuing until the end of the study. The urinary bladders of all the rats were weighed and examined grossly for lesions, and all masses were submitted for pathological evaluation. A dose-dependent preventive effect of cranberry treatment was observed, with a reduced number of urinary bladder cancers (38%) in the 1.0 ml/rat/day group versus the control group. The cranberry extract neither affected body weight gain nor caused other signs of toxicity. For the metabolic studies, serum and urine were collected at 4 and 12 h after the administration of the cranberry juice concentrate and were analyzed by LC-MS/MS. Quercetin and its methylated derivative were detected in the urine samples. However, no quercetin was detected in the serum samples, indicating its poor bioavailability. These data suggest that components of cranberries may be effective in preventing urinary bladder carcinogenesis.
Abstract: No abstract - Purpose: The aim of our correspondence is to submit the results of a small study (the first in a Greek population to our knowledge) about administering cranberries in the form of capsules to healthy postmenopausal women with recurrent UTIs.
Abstract: OBJECTIVE: To determine the effectiveness of cranberry supplement at preventing urinary tract infections (UTIs) in persons with spinal cord injury (SCI).
DESIGN: A prospective, double-blinded, placebo-controlled, crossover study.
PARTICIPANTS: 21 individuals with neurogenic bladders secondary to SCI.
MAIN OUTCOME MEASURES: Favorable or unfavorable response of cranberry supplement vs placebo on urinary bacterial counts and white blood cell (WBC) counts and the combination of bacterial and WBC counts.
METHODS: Individuals with neurogenic bladders due to SCI were recruited and randomly assigned to standardized 400-mg cranberry tablets or placebo 3 times a day for 4 weeks. After 4 weeks and an additional 1-week ""washout period,"" participants were crossed over to the other group. Participants were seen weekly, during which a urine analysis was obtained. UTI was defined as significant bacterial or yeast colony counts in the urine and elevated WBC counts (WBC count > or = 10 per high power field) in centrifuged urine. Participants with symptomatic infections were treated with appropriate antibiotics for 7 days and restarted on the cranberry tablet/ placebo after a 7-day washout period. Urinary pH between the cranberry and placebo groups was compared weekly. Data were analyzed using the Ezzet and Whitehead's random effect approach.
RESULTS: There was no statistically significant treatment (favorable) effect for cranberry supplement beyond placebo when evaluating the 2 treatment groups for bacterial count, WBC count, or WBC and bacterial counts in combination. Urinary pH did not differ between the placebo and cranberry groups.
CONCLUSION: Cranberry tablets were not found to be effective at changing urinary pH or reducing bacterial counts, urinary WBC counts, or UTIs in individuals with neurogenic bladders. Further long-term studies evaluating specific types of bladder management and UTIs will help to determine whether there is any role for the use of cranberries in individuals with neurogenic bladders.
Abstract: OBJECTIVE: To investigate the potential influence of cranberry juice on urinary biochemical and physicochemical risk factors associated with the formation of calcium oxalate kidney stones, as this product might affect the chemical composition of urine.
SUBJECTS AND METHODS: Urinary variables were assessed in a randomized cross-over trial in 20 South African men (students) with no previous history of kidney stones. The first group of 10 subjects drank 500 mL of cranberry juice diluted with 1500 mL tap water for 2 weeks, while the second group drank 2000 mL of tap water for the same period. This was followed by a 2-week 'washout' period before the two groups crossed over. During the experimental phase subjects kept a 3-day food diary to assess their dietary and fluid intakes; 24-h urine samples were collected at baseline and on day 14 of the trial periods, and analysed using modern laboratory techniques. Urine analysis data were used to calculate the relative urinary supersaturations of calcium oxalate, uric acid and calcium phosphate. Data were assessed statistically by analysis of variance.
RESULTS: The ingestion of cranberry juice significantly and uniquely altered three key urinary risk factors. Oxalate and phosphate excretion decreased while citrate excretion increased. In addition, there was a decrease in the relative supersaturation of calcium oxalate, which tended to be significantly lower than that induced by water alone.
CONCLUSION: Cranberry juice has antilithogenic properties and, as such, deserves consideration as a conservative therapeutic protocol in managing calcium oxalate urolithiasis.
Abstract: Ulcer-associated dyspepsia is caused by infection with Helicobacter pylori. H. pylori is linked to a majority of peptic ulcers. Antibiotic treatment does not always inhibit or kill H. pylori with potential for antibiotic resistance. The objective of this study was to determine the potential for using phenolic phytochemical extracts to inhibit H. pylori in a laboratory medium. Our approach involved the development of a specific phenolic profile with optimization of different ratios of extract mixtures from oregano and cranberry. Subsequently, antimicrobial activity and antimicrobial-linked urease inhibition ability were evaluated. The results indicated that the antimicrobial activity was greater in extract mixtures than in individual extracts of each species. The results also indicate that the synergistic contribution of oregano and cranberry phenolics may be more important for inhibition than any species-specific phenolic concentration. Further, based on plate assay, the likely mode of action may be through urease inhibition and disruption of energy production by inhibition of proline dehydrogenase at the plasma membrane.
Abstract: AIM: To study isolation and chemical characterization of pectin derived from the common cranberry Vaccinium oxycoccos L. (oxycoccusan OP) and the testing of its preventive effect on experimental colitis.
METHODS: Mice were administrated orally with OP two days prior to a rectal injection of 5% acetic acid and examined for colonic damage 24 h later. Colonic inflammation was characterized by macroscopical injury and enhanced levels of myeloperoxidase activity measured spectrophotometrically with o-phenylene diamine as the substrate. The mucus contents of the colon were determined by the Alcian blue dye binding method. Vascular permeability was estimated using 4% Evans blue passage after i.p. injection of 0.05 mol/L acetic acid.
RESULTS: In the mice treated with OP, colonic macroscopic scores (1.1+/-0.4 vs 2.7, P<0.01) and the total square area of damage (10+/-2 vs 21+/-7, P<0.01) were significantly reduced when compared with the vehicle-treated colitis group. OP was shown to decrease the tissue myeloperoxidase activity in colons (42+/-11 vs 112+/-40, P<0.01) and enhance the amount of mucus of colitis mice (0.9+/-0.1 vs 0.4+/-0.1, P<0.01). The level of colonic malondialdehyde was noted to decrease in OP-pretreated mice (3.6+/-0.7 vs 5.1+/-0.8, P<0.01). OP was found to decrease the inflammatory status of mice as was determined by reduction of vascular permeability (161+/-34 vs 241+/-21, P<0.01). Adhesion of peritoneal neutrophils and macrophages was also shown to decrease after administration of OP (141+/-50 vs 235+/-37, P<0.05).
CONCLUSION: Thus, a preventive effect of pectin from the common cranberry, namely oxycoccusan OP, on acetic acid-induced colitis in mice was detected. A reduction of neutrophil infiltration and antioxidant action may be implicated in the protective effect of oxycoccusan.
Abstract: Cranberry juice has long been believed to benefit the prevention and treatment of urinary tract infections (UTIs). As the first step in the development of infection, bacterial adhesion is of great research interest, yet few studies have addressed molecular level adhesion in this context. P-fimbriated Escherichia coli play a major role in the development of a serious type of UTI, acute pyelonephritis. Experiments were conducted to investigate the molecular-scale effects of cranberry juice on two E. coli strains: HB101, which has no fimbriae, and the mutant HB101pDC1 which expresses P-fimbriae. Atomic force microscopy (AFM) was used to investigate both bacterial surface characteristics and adhesion forces between a probe surface (silicon nitride) and the bacteria, providing a direct evaluation of bacterial adhesion and interaction forces. Cranberry juice affected bacterial surface polymer and adhesion behavior after a short exposure period (<3 h). Cranberry juice affected the P-fimbriated bacteria by decreasing the adhesion forces between the bacterium and tip and by altering the conformation of the surface macromolecules on E. coli HB101pDC1. The equilibrium length of polymer (P-fimbriae) on this bacterium decreased from approximately 148 to approximately 48 nm upon being exposed to cranberry juice. Highly acidic conditions were not necessary for the prevention of bacterial adhesion, since neutralization of cranberry juice solutions to pH = 7.0 allowed us to observe differences in adhesion between the E. coli strains. Our results demonstrate molecular-level changes in the surfaces of P-fimbriated E. coli upon exposure to neutralized cranberry juice.
Abstract: (Epi)catechins are associated with many health benefits in humans. However, their bioavailability, excretory pattern, and extent of conjugation in animals fed different sources or levels in the diet are not well documented. Two experiments were conducted to investigate the urinary excretion of (epi)catechins after feeding of different types of berries or different levels of the same berry source to rats. Experiment 1 investigated the effects of feeding a commercially available concentrated cranberry powder (CCP) at three different levels, 3.3, 6.6, and 33 g/kg of diet, whereas experiment 2 investigated the effect of feeding freeze-dried whole cranberry (CB), blueberry (BB), or black raspberry (BRB) powder at 50 g/kg of diet. Both experiments had an AIN-93-based control and a high-fructose diet (53-65% of the diet) to which was added three levels of CCP in experiment 1 and CB, BB, and BRB in experiment 2. (Epi)catechins were excreted as free and conjugated in both intact and methylated forms. Excretion of conjugated (epi)catechins was as high as 60% of the total consumed in some cases. A majority of both catechins and epicatechins excreted in the urine was in a methylated form. Excretion of epicatechins, including their methylated forms, ranged from 30 to 47% of the ingested amount, whereas that of catechins, including their methylated forms, ranged from 9 to 31%. Urinary excretion of (epi)catechins was dose dependent and increased with the amount of (epi)catechins present in the diet. On the basis of the excretory pattern of (epi)catechins in the urine, data suggested that the bioavailability of epicatechins may be higher than that of catechins and that (epi)catechins may be more available from blueberries compared to cranberries.
Abstract: Dietary flavonoids can be converted into phenolic acids by colonic microflora. Phenolic acids can then be absorbed into the circulation and may contribute to the health-promoting effects of the parent compounds. Phenolic acids can be further metabolized in other tissues via methylation and conjugation with glucuronide or sulfate. The objectives of this study were to identify and quantify the urinary excretion of 19 phenolic acids and their conjugates in rats fed three levels of a concentrated cranberry powder (3.3, 6.6, and 33 mg/kg of diet). The basic diet used was AIN93G diet containing very low amounts of any polyphenolic compounds. Of the phenolic acids studied, the amounts excreted varied by 4 orders of magnitude, with hippuric acid being excreted in the highest quantities. Amounts of 4-hydroxyphenylacetic acid (4HPAA), 3-hydroxyphenylacetic acid (3HPAA), 3-hydroxyphenylpropionic acid (3HPPA), and 4-hydroxycinnamic acid (4HCA) excreted were in the range of 18-33 microg/mg creatinine in animals fed the highest level of cranberry powder, whereas phenylacetic acid (PAA), gallic acid (GA), 3,4-dihydroxyphenylacetic acid (34HPAA), 3,4-dihydroxybenzoic acid (34HBA), 3,4-dihydroxycinnamic acid (34HCA), and 4-hydroxy-3-methoxycinnamic acid (FA) were excreted in the urine in concentrations of 0.1-2 microg/mg creatinine. As the amount of cranberry in the diet was increased, the amount of 4HPAA excreted decreased but the percentage of conjugated 4HPAA excreted increased (from 57 to 91%). For other phenolic acids analyzed, the percentage excreted in the conjugated form was approximately constant across levels of cranberry in the diet and ranged from 65 to 100% for the individual phenolic acids. Studies of bioactivity and health effects need to consider more than just the compound(s) in the food, because they can be metabolized to other lower molecular weight compounds, which in turn may also be methylated or conjugated in some form that may affect the perceived health effects.
Abstract: 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.
Abstract: The purpose of this study was to examine risk factors for symptomatic vulvovaginal candidiasis episodes among women with recurrent vulvovaginal candidiasis (defined as >/=4 vulvovaginal candidiasis episodes in 1 year) who were receiving maintenance antifungal therapy.
STUDY DESIGN: A prospective study of 65 women aged >/=18 years with recurrent vulvovaginal candidiasis who attended vaginitis clinics in Detroit, Mich, and Philadelphia, Pa.
RESULTS: The 9-month risk of vulvovaginal candidiasis recurrence was 41.8%. Almost two fifths of the women reported activity limitations because of vulvovaginal candidiasis episodes, most or all of the time. Younger women and those women with a history of bacterial vaginosis were at increased risk of vulvovaginal candidiasis episodes. Behavioral factors that were associated significantly with increasing vulvovaginal candidiasis recurrence >/=2- fold included wearing pantyliners or pantyhose and consuming cranberry juice or acidophilus-containing products.
CONCLUSION: The use of pantyliners or pantyhose, consumption of cranberry juice or acidophil-containing products, a history of bacterial vaginosis, and age <40 years were positively associated with a symptomatic vulvovaginal candidiasis episode.
Abstract: Cranberry, which is rich in polyphenols, including anthocyanins and proanthocyanidins, has been found to have various effects beneficial to human health, including prevention of urinary tract infections. These effects have been associated with polyphenols in the fruit. We investigated the excretion of anthocyanins in human urine after ingestion of cranberry juice. Eleven healthy volunteers consumed 200 ml of cranberry juice containing 650.8 microg total anthocyanins. Urine samples were collected within 24 h before and after consumption. Six of 12 anthocyanins identified in cranberry were quantified in human urine by HPLC coupled with electrospray ionization and tandem mass spectrometry (HPLC-ESI-MS-MS). Among these, peonidin 3-O-galactoside, the second most plentiful anthocyanin in the juice, was found most abundantly in urine within 24 h, corresponding to 41.5 nmol (56.1% of total anthocyanins). The urinary levels of anthocyanins reached a maximum between 3 and 6 h after ingestion, and the recovery of total anthocyanins in the urine over 24 h was estimated to be 5.0% of the amount consumed. This study found high absorption and excretion of cranberry anthocyanins in human urine.
Abstract: AIMS: To investigate the effects of berries and berry phenolics on pathogenic intestinal bacteria and to identify single phenolic compounds being responsible for antimicrobial activity.
METHODS AND RESULTS: Antimicrobial activity of eight Nordic berries and their phenolic extracts and purified phenolic fractions were measured against eight selected human pathogens. Pathogenic bacterial strains, both Gram-positive and Gram-negative, were selectively inhibited by bioactive berry compounds. Cloudberry and raspberry were the best inhibitors, and Staphylococcus and Salmonella the most sensitive bacteria. Phenolic compounds, especially ellagitannins, were strong inhibitory compounds against Staphylococcus bacteria. Salmonella bacteria were only partly inhibited by the berry phenolics, and most of the inhibition seemed to originate from other compounds, such as organic acids. Listeria strains were not affected by berry compounds, with the exception of cranberry. Phenolic compounds affect the bacteria in different mechanisms.
CONCLUSIONS: Berries and their phenolics selectively inhibit the growth of human pathogenic bacteria.
SIGNIFICANCE AND IMPACT OF THE STUDY: Antimicrobial properties of berries could be utilized in functional foods. Furthermore these compounds would be of high interest for further evaluation of their properties as natural antimicrobial agents for food and pharmaceutical industry
Abstract: Cranberries have long been the focus of interest for their beneficial effects in preventing urinary tract infections (UTIs). Cranberries contain 2 compounds with antiadherence properties that prevent fimbriated Escherichia coli from adhering to uroepithelial cells in the urinary tract. Approximately 1 dozen clinical trials have been performed testing the effects of cranberries on the urinary tract. However, these trials suffer from a number of limitations. Most importantly, the trials have used a wide variety of cranberry products, such as cranberry juice concentrate, cranberry juice cocktail, and cranberry capsules, and they have used different dosing regimens. Further research is required to clarify unanswered questions regarding the role of cranberries in protecting against UTI in general and in women with anatomical abnormalities in particular.
Abstract: The majority of infectious diseases are initiated by the adhesion of pathogenic organisms to the tissues of the host. In many cases this adhesion is mediated by lectins present on the surface of the infectious organism that bind to complementary carbohydrates on the surface of the host tissues. Soluble carbohydrates recognized by the bacterial lectins block the adhesion of the bacteria to animal cells in vitro. Moreover, such carbohydrates have been shown to protect against experimental infection by lectin-carrying bacteria of different mammals, such as mice, rabbits, calves, and monkeys. Agents other than carbohydrates also block adhesion, as demonstrated with cranberry juice as well as with low and high molecular weight preparations isolated from the juice. Both kinds of preparation inhibited the adhesion in vitro of Escherichia coli to different animal cells. In addition, the high molecular weight material acted similarly on the adhesion of Helicobacter pylori to human gasrointenstinal cells, and on the coaggregation of oral bacteria. Furthermore, in limited clinical studies regular drinking of cranberry juice had a significant preventive effect on bacteriuria, and the high molecular weight constituent of the juices was also effective in decreasing the salivary level of Streptococus mutans, the major cause of tooth decay. Because the inhibitors of adhesion examined are not bactericidal, the selection of resistant inhibitor strains is unlikely to occur. Together, these findings may lead to new therapeutic strategies that are in dire need because of the world-wide increase in antibiotic resistant bacteria.
Abstract: The sensitivity of a large number of antibiotic-resistant and nonresistant Helicobacter pylori isolates to the antiadhesion effect of a high-molecular-mass, nondialysable constituent of cranberry juice was tested. Confluent monolayers of gastric cell line in microtiter plate wells were exposed to bacterial suspensions prepared from 83 H. pylori isolates from antibiotic-treated and untreated patients in the presence and absence of the cranberry constituent. Urease assay was used to calculate the percentage of adhesion inhibition. In two thirds of the isolates, adhesion to the gastric cells was inhibited by 0.2 mg/mL of the nondialysable material. There was no relationship between the antiadhesion effect of the cranberry material and metronidazole resistance in isolates from either treated or untreated patients (N=35). Only 13 isolates (16%) were resistant to both the nondialysable material and metronidazole, and 30 (36%) were resistant to the nondialysable material alone. There was no cross-resistance to the nondialysable material and metronidazole. These data suggest that a combination of antibiotics and a cranberry preparation may improve H. pylori eradication.
Abstract: Several forces are driving an expanded use of nutraceuticals, particularly functional foods and probiotics, as instruments of the restoration and maintenance of well-being. These include consumer desire to use natural rather than pharmaceutical products, the mounting scientific evidence that shows efficacy of certain nutraceutical products, and the increasing cost and continued failure of drugs to cure or prevent disease. There is now a strong scientific basis for use of cranberries to reduce the risk of E. coli adhesion to bladder cells and the onset of urinary tract infection. There is also a mechanistic basis and clinical support for use of Lactobacillus strains such as L. rhamnosus GR-1 and L. fermentum RC-14 to colonize the intestine and vagina and reduce the risk of intestinal and urogenital infections. For such alternative approaches to be successful, scientific rigor must be backed by public education and physician acceptance. Given the emergence of virulent and multidrug-resistant pathogens, time is not on our side.
Abstract: Previous investigations showed that a high molecular mass, non-dialyzable material (NDM) from cranberries inhibits the adhesion of a number of bacterial species and prevents the co-aggregation of many oral bacterial pairs. In the present study we determined the effect of mouthwash supplemented with NDM on oral hygiene. Following 6 weeks of daily usage of cranberry-containing mouthwash by an experimental group (n = 29), we found that salivary mutans streptococci count as well as the total bacterial count were reduced significantly (ANOVA, P < 0.01) compared with those of the control (n = 30) using placebo mouthwash. No change in the plaque and gingival indices was observed. In vitro, the cranberry constituent inhibited the adhesion of Streptococcus sobrinus to saliva-coated hydroxyapatite. The data suggest that the ability to reduce mutans streptococci counts in vivo is due to the anti-adhesion activity of the cranberry constituent.
Abstract: No abstract - The high-molecular-weight inhibitor of adhesin was partially purified from cranberry juice by gel-filtration chromatography. The product was heat-stable, resistant to trypsin, and nondialysable, and it inhibited the MR adhesin of al 20 urinary isolates tested in concentrations of 12 to 25 µg per milliliter. On the basis of these results, together with those of earlier studies, we suggest that the antiadhesive agents in juices from vaccinium berries may act in the gut (the source of most uropathogens), in the bladder, or both by preventing colonization of these sites.
Abstract: Dental biofilm harbouring oral bacteria is highly correlated with the progression of dental diseases. Disruption of biofilm formation via anti-adhesion agents is an alternative means to the antibacterial approach. Previous studies have shown that high molecular weight non-dialysable material (NDM) derived from cranberry juice inhibits the adhesion of Escherichia coli and the coaggregation of a variety of oral bacteria. In addition, it inhibits the formation of glucans and fructans synthesised by GTF and FTF. In the present study, we examined the anti-adhesion effect of NDM on S. sobrinus. NDM promoted desorption of S. sobrinus from biofilm in the presence and absence of extracellular glucans and fructans, although the effect was more pronounced in the absence of these polysaccharides. Precoating of the bacteria with NDM reduced their ability to form biofilm. Our results indicate that NDM could be exploited as an anti-biofilm agent.
Abstract: Cranberry juice contains high molecular weight materials (NDM) that inhibit bacterial adhesion to host cells as well as the co-aggregation of many oral bacteria. Because of its broad-spectrum activity, we investigated NDM's potential for inhibiting influenza virus adhesion to cells, and subsequent infectivity. Hemagglutination (HA) of red blood cells (RBC) caused by representatives of both influenza virus A subtypes (H1N1)and H3N2) and the B type was inhibited by NDM at concentrations of 125 microg/ml or lower, which is at least 20-fold lower than that usually found in cranberry juice. A dose-response effect of NDM on HA was demonstrated. The infectivity of the A and B types was significantly reduced by preincubation with NDM (250 microg/ml), as reflected by the lack of cytopathic effect on Madine-Darby canine kidney (MDCK) cells and the lack of HA activity in the media of infected cells. The effect of NDM was also tested after A or B type viruses were allowed to adsorb to and penetrate the cells. Various levels of reduction in virus tissue culture infective dose TCID50 were observed. The effect was most pronounced when NDM was added several times to the infected MDCK cells. Our cumulative findings indicate that the inhibitory effect of NDM on influenza virus adhesion and infectivity may have a therapeutic potential.
Abstract: One of the major health benefits attributed to the ingestion of cranberry juice is the maintenance of urinary tract health. Traditionally, the juice was thought to cause acidification of the urine resulting in a bacteriostatic effect. However, recent research has demonstrated that a bacterial antiadhesion mechanism is responsible. Proanthocyanidins with unique molecular structures have been isolated from cranberry fruit that exhibit potent bacterial antiadhesion activity. Little is known about the bioavailability and structure-activity relationships of cranberry proanthocyanidins. Data on how certain structural features of the molecules can influence bioactivity and bioavailability are reviewed.
Abstract: BACKGROUND: Previous studies have shown that high molecular-weight non-dialysable material derived from cranberry juice (NDM) inhibits co-aggregation of a variety of oral bacteria.
OBJECTIVES: In the present study, we examined the effect of NDM on several constituents of the dental biofilm, glucosyltransferase (GTF) and fructosyltransferase (FTF), as well as on the adhesion of Streptococcus sobrinus.
RESULTS: The activity of immobilized and soluble GTF and FTF was inhibited by NDM (P > 0.05). NDM also inhibited adhesion of S. sobrinus to hydroxyapatite (P < 0.05).
CONCLUSIONS: Our results indicate that NDM may affect biofilm formation. One of the proposed mechanisms is via inhibition of extracellular polysaccharide synthesis, which promote the sucrose-dependent adhesion of oral bacteria as S. sobrinus.
Abstract: OBJECTIVE: To determine whether antibacterial effects of cranberry extract will reduce or eliminate bacteriuria and pyuria in persons with spinal cord injury (SCI).
DESIGN: Randomized, double-blind, placebo-controlled study.
PARTICIPANTS: Participants were people with SCI residing in the community who were 1 year or longer postinjury with neurogenic bladder managed by intermittent catheterization or external collection device and a baseline urine culture demonstrating at least 10(5) colonies per milliliter of bacteria.
METHODS: Each participant ingested 2 g of concentrated cranberry juice or placebo in capsule form daily for 6 months. Baseline urinalysis and cultures were performed at the time of the initial clinic visit and monthly for 6 months. Microbiologic data were evaluated using analysis of variance with repeated measures.
RESULTS: Twenty-six persons received cranberry extract and 22 persons received placebo. There were no differences or trends detected between participants and controls with respect to number of urine specimens with bacterial counts of at least 10(4) colonies per milliliter, types and numbers of different bacterial species, numbers of urinary leukocytes, urinary pH, or episodes of symptomatic urinary tract infection.
CONCLUSION: Cranberry extract taken in capsule form did not reduce bacteriuria and pyuria in persons with SCI and cannot be recommended as a means to treat these conditions.
Abstract: No abstract - Introduction: Cranberry juice has been shown to have a significant effect in preventing urinary tract infections (UTIs) in a number of clinical trials. This property of cranberry juice has been attributed to an ability to inhibit bacterial adherence to cells and possibly its urine acidification effects. However, cranberry juice’s antibacterial activity in urine remains unknown. Although a preliminary study by Lee et al. found that concentrated cranberry juice has some antibacterial activity, cranberry juice was studied, not the resultant urine samples. Therefore, our study investigated whether cranberry juice has antibacterial effects in urine. We excluded acidification as a possible antibacterial factor.
Abstract: PURPOSE OF REVIEW: The underlying cause of catheter-associated urinary tract infection is biofilm formation by uropathogens on the urinary catheter. Biofilm is a relatively new concept in medicine, and current measures to prevent biofilm formation are inadequate. Considerable work is being done in this area, but little clinical progress has been made. The purpose of this review is to analyze recent publications concerning prevention of catheter-associated urinary tract infection.
RECENT FINDINGS: Several recent studies have elucidated aspects of biofilm formation in catheter-associated urinary tract infection. Other researchers are working on methods to disrupt biofilm formation on catheter surfaces. At the same time, the magnitude of the problem of catheter-associated urinary tract infection has increased awareness of the effectiveness of basic infection control measures. A modern approach to infection control may include computerized ordering systems that minimize unnecessary days of catheterization. Finally, consumption of cranberry juice products and bacterial interference are two novel approaches to urinary tract infection prevention.
SUMMARY: Biofilm-disrupting strategies offer promise for the future but have little immediate applicability. Implementation of infection control measures to improve catheter function and remove unnecessary catheters can be done at the present time. In general, prevention of catheter-associated urinary tract infection remains an elusive goal. More basic research at the level of pathogenesis is needed so that novel strategies can be designed.
Abstract: A-type cranberry proanthocyanidins (AC-PACs) have recently been reported to be beneficial for human health, especially urinary tract health. The effect of these proanthocyanidins on periodontitis, a destructive disease of tooth-supporting tissues, needs to be investigated. The purpose of this study was to investigate the effects of AC-PACs on various virulence determinants of Porphyromonas gingivalis as well as on the inflammatory response of oral epithelial cells stimulated by this periodontopathogen. We examined the effects of AC-PACs on P. gingivalis growth and biofilm formation, adherence to human oral epithelial cells and protein-coated surfaces, collagenase activity, and invasiveness. We also tested the ability of AC-PACs to modulate the P. gingivalis-induced inflammatory response by human oral epithelial cells. Our results showed that while AC-PACs neutralized all the virulence properties of P. gingivalis in a dose-dependent fashion, they did not interfere with growth. They also inhibited the secretion of interleukin-8 (IL-8) and chemokine (C-C motif) ligand 5 (CCL5) but did not affect the secretion of IL-6 by epithelial cells stimulated with P. gingivalis. This anti-inflammatory effect was associated with reduced activation of the nuclear factor-kappaB (NF-kappaB) p65 pathway. AC-PACs may be potentially valuable bioactive molecules for the development of new strategies to treat and prevent P. gingivalis-associated periodontal diseases.
Abstract: This study assessed the effect of an 8 week consumption of dried cranberry juice (DCJ) on 65 healthy young women. Basic biochemical and hematological parameters, antioxidant status, presence of metabolites in urine, and urine ex vivo antiadherence activity were determined throughout the trial. A 400 mg amount of DCJ/day had no influence on any parameter tested. A 1200 mg amount of DCJ/day resulted in a statistically significant decrease in serum levels of advanced oxidation protein products. This specific protective effect against oxidative damage of proteins is described here for the first time. Urine samples had an inhibitory effect on the adhesion of uropathogenic Escherichia coli strains, but no increase in urine acidity was noted. Hippuric acid, isomers of salicyluric and dihydroxybenzoic acids, and quercetin glucuronide were identified as the main metabolites. In conclusion, cranberry fruits are effective not only in the prevention of urinary tract infection but also for the prevention of oxidative stress.
Abstract: No abstract - Introduction: Cranberry is among the most commonly used natural health products in North America. Commercial cranberry products commonly are derived from the Vaccinium oxycoccos and V macrocarpon species, which are cultivated widely across the Northern hemisphere. Seventy percent of the cranberry crop in North America is controlled by a single manufacturer. Historically, cranberry fruits and leaves have been used for wound dressings, urinary disorders, diabetes, blood poisoning, diarrhea, and liver problems. More recently, cranberry has been used to prevent urinary tract infections (UTIs) and dental plaque. The scientific evidence regarding medicinal uses of cranberry in pediatric populations is presented in this article.
Abstract: BACKGROUND: Cranberries have been used widely for several decades for the prevention and treatment of urinary tract infections (UTIs).
OBJECTIVES: To assess the effectiveness of cranberry products in preventing UTIs in susceptible populations.
SEARCH STRATEGY: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL in The Cochrane Library) and the Internet. We contacted companies involved with the promotion and distribution of cranberry preparations and checked reference lists of review articles and relevant studies. Date of last search: January 2007.
SELECTION CRITERIA: All randomised controlled trials (RCTs) or quasi-RCTs of cranberry products for the prevention of UTIs in all populations.
DATA COLLECTION AND ANALYSIS: Two authors independently assessed and extracted information. Information was collected on methods, participants, interventions and outcomes (UTIs - symptomatic and asymptomatic, side effects, adherence to therapy). Relative risk (RR) were calculated where appropriate, otherwise a narrative synthesis was undertaken. Quality was assessed using the Cochrane criteria.
MAIN RESULTS: Ten studies (n = 1049, five cross-over, five parallel group) were included. Cranberry/cranberry-lingonberry juice versus placebo, juice or water was evaluated in seven studies, and cranberries tablets versus placebo in four studies (one study evaluated both juice and tablets). Cranberry products significantly reduced the incidence of UTIs at 12 months (RR 0.65, 95% CI 0.46 to 0.90) compared with placebo/control. Cranberry products were more effective reducing the incidence of UTIs in women with recurrent UTIs, than elderly men and women or people requiring catheterisation. Six studies were not included in the meta-analyses due to methodological issues or lack of available data. However, only one reported a significant result for the outcome of symptomatic UTIs. Side effects were common in all studies, and dropouts/withdrawals in several of the studies were high.
AUTHORS' CONCLUSIONS: There is some evidence that cranberry juice may decrease the number of symptomatic UTIs over a 12 month period, particularly for women with recurrent UTIs. It's effectiveness for other groups is less certain. The large number of dropouts/withdrawals indicates that cranberry juice may not be acceptable over long periods of time. It is not clear what is the optimum dosage or method of administration (e.g. juice, tablets or capsules). Further properly designed studies with relevant outcomes are needed.
Abstract: Urinary tract infection (UTI) refers to the presence of clinical signs and symptoms arising from the genitourinary tract plus the presence of one or more micro-organisms in the urine exceeding a threshold value for significance (ranges from 102 to 103 colony-forming units/mL). Infections are localized to the bladder (cystitis), renal parenchyma (pyelonephritis) or prostate (acute or chronic bacterial prostatitis). Single UTI episodes are very common, especially in adult women where there is a 50-fold predominance compared with adult men. In addition, recurrent UTIs are also common, occurring in up to one-third of women after first-episode UTIs. Recurrences requiring intervention are usually defined as two or more episodes over 6 months or three or more episodes over 1 year (this definition applies only to young women with acute uncomplicated UTIs). A cornerstone of prevention of UTI recurrence has been the use of low-dose once-daily or post-coital antimicrobials; however, much interest has surrounded non-antimicrobial-based approaches undergoing investigation such as use of probiotics, vaccines, oligosaccharide inhibitors of bacterial adherence and colonization, and bacterial interference with immunoreactive extracts of Escherichia coli. Local (intravaginal) estrogen therapy has had mixed results to date. Cranberry products in a variety of formulations have also undergone extensive evaluation over several decades in the management of UTIs. At present, there is no evidence that cranberry can be used to treat UTIs. Hence, the focus has been on its use as a preventative strategy. Cranberry has been effective in vitro and in vivo in animals for the prevention of UTI. Cranberry appears to work by inhibiting the adhesion of type I and P-fimbriated uropathogens (e.g. uropathogenic E. coli) to the uroepithelium, thus impairing colonization and subsequent infection. The isolation of the component(s) of cranberry with this activity has been a daunting task, considering the hundreds of compounds found in the fruit and its juice derivatives. Reasonable evidence suggests that the anthocyanidin/proanthocyanidin moieties are potent antiadhesion compounds. However, problems still exist with standardization of cranberry products, which makes it extremely difficult to compare products or extrapolate results. Unfortunately, most clinical trials have had design deficiencies and none have evaluated specific key cranberry-derived compounds considered likely to be active moieties (e.g. proanthocyanidins). In general, the preventive efficacy of cranberry has been variable and modest at best. Meta-analyses have established that recurrence rates over 1 year are reduced approximately 35% in young to middle-aged women. The efficacy of cranberry in other groups (i.e. elderly, paediatric patients, those with neurogenic bladder, those with chronic indwelling urinary catheters) is questionable. Withdrawal rates have been quite high (up to 55%), suggesting that these products may not be acceptable over long periods. Adverse events include gastrointestinal intolerance, weight gain (due to the excessive calorie load) and drug-cranberry interactions (due to the inhibitory effect of flavonoids on cytochrome P450-mediated drug metabolism). The findings of the Cochrane Collaboration support the potential use of cranberry products in the prophylaxis of recurrent UTIs in young and middle-aged women. However, in light of the heterogeneity of clinical study designs and the lack of consensus regarding the dosage regimen and formulation to use, cranberry products cannot be recommended for the prophylaxis of recurrent UTIs at this time.
Abstract: Catheter associated urinary tract infections (CAUTI) linked with the uropathogens Escherichia coli (E. coli) and Enterococcus faecalis (E. faecalis) account for the majority of nosocomial infections acquired in the clinical environment. Because these infections develop following initial adhesion of the bacterial pathogens to the catheter surface, there is increased interest in developing effective methods to inhibit attachment of cells to biomaterials used in the manufacture of indwelling devices. High molecular weight proanthocyanidins (PAC) extracted from the North American cranberry (Vaccinium macrocarpon) were examined for their potential to reduce the initial adhesion of uropathogenic bacteria (E. coli CFT073 and E. faecalis 29212) to two model biomaterials, poly(vinyl chloride) (PVC) and polytetrafluoroethylene (PTFE). Well-controlled experiments conducted in a parallel-plate flow chamber (PPFC) demonstrated decreased attachment of both bacteria to PVC and PTFE when either the bacteria, biomaterial or both surfaces were treated with PAC. Most significant inhibition of bacterial adhesion was observed for the condition where both the bacteria and biomaterial surfaces were coated with PAC. Additional experiments conducted with nonbiological model particles demonstrate comparable extents of adhesion inhibition, supporting a nonbiospecific mechanism of PAC action. The results of this study are promising for the implementation of PAC in the clinical milieu for prevention of device associated infection as the proposed functional modification is independent of antibacterial mechanisms that may give rise to resistant strains.
Abstract: Matrix metalloproteinases (MMPs) produced by resident and inflammatory cells in response to periodontopathogens play a major role in periodontal tissue destruction. Our aim was to investigate the effects of A-type cranberry proanthocyanidins (AC-PACs) on: (i) the production of various MMPs by human monocyte-derived macrophages stimulated with Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS), and (ii) the catalytic activity of recombinant MMP-1 and MMP-9. The effects of AC-PACs on the expression of 5 protein kinases and the activity of nuclear factor-kappa B (NF-kappaB) p65 in macrophages stimulated with LPS were also monitored. Our results indicated that AC-PACs inhibited the production of MMPs in a concentration-dependent manner. Furthermore, the catalytic activity of MMP-1 and MMP-9 was also inhibited. The inhibition of MMP production was associated with reduced phosphorylation of key intracellular kinases and the inhibition of NF-kappaB p65 activity. AC-PACs thus show potential for the development of novel host-modulating strategies to inhibit MMP-mediated tissue destruction during periodontitis.
Abstract: Recent studies brought evidence regarding the potential beneficial effects of cranberry polyphenols for periodontal infections. In this study, we evaluated the capacity of a proanthocyanidin-rich cranberry fraction to protect macrophages and oral epithelial cells against cytotoxicity induced by bacterial components. U937 cells, differentiated into adherent macrophage-like cells, as well as oral epithelial cells were treated with cell wall or lipopolysaccharide preparations from periodontopathogens. Cell viability was monitored using a commercial MTT (3-[4,5-diethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. The cytoprotective effect was evaluated by pre-incubating human cells with a proanthocyanidin-rich cranberry fraction prior to treatment with the bacterial components at toxic concentrations. Among the various bacterial components tested, Peptostreptotoccus micros cell wall was found to be the most toxic for macrophages and epithelial cells and was thus selected for further analyses. Treatment of monocyte-derived macrophages with cell wall of P. micros (20 microg/ml) decreased the cell viability by approximately 50%. Adding the cranberry fraction prior to treating cells with P. micros cell wall dose-dependently protected monocyte-derived macrophages from the toxic effect. A dose-dependent cytoprotective effect of the cranberry fraction was also observed with oral epithelial cells treated with P. micros cell wall. This study suggests that cranberry polyphenols may exert a protective effect for host cells against the toxicity induced by bacterial components
Abstract: OBJECTIVE: Bacteriuria is a usual complication of enterocystoplasty following cystectomy. Cranberry products may decrease the number of urinary tract infections because of a non-dialysable compound, a condensed tannin, the proanthocyanidin (PAC) type A. This study determined the effectiveness of treatment with a cranberry preparation highly dosed in proanthocyanidin A in prevention of repeated bacteriuria in patients with an ileal enterocystoplasty.
MATERIAL AND METHODS: Between November 2004 and November 2009, a controlled study was open to patients seen in consultation for follow-up after a radical cystectomy and ileal cystoplasty. Patients had a history of repeated urinary infection and/or bacteriuria during the pretreatment phase. During the treatment phase, patients received a cranberry (Vaccinium macrocarpon) preparation highly dosed in proanthocyanidin A (36 mg measured by the dimethylaminocinnamaldehyde method), one capsule a day. The primary endpoint was the absence of bacteria in urine culture. The secondary endpoints were the presence or absence of symptoms (pain, fever), continence status and upper excretory tract enlargement. Each patient was his or her own historical control.
RESULTS: Fifteen patients were included. The median duration of the period without treatment with cranberry compound was 18.5 (1-93) months. The median duration of the period with treatment with cranberry compound was 32.8 (13-60) months. There was a significant decrease in the number of positive urine cultures during cranberry compound treatment.
CONCLUSIONS: Treatment with a cranberry compound seems to be effective in reducing asymptomatic bacteriuria in patients with an ileal enterocystoplasty. These results need to be validated by further double-blind randomized studies.
Abstract: STUDY DESIGN: Randomized, double blind, placebo-controlled trial with a crossover design.
OBJECTIVE: To evaluate cranberry tablets for the prevention of urinary tract infection (UTI) in spinal cord injured (SCI) patients.
SETTING: Spinal Cord Injury Unit of a Veterans Administration Hospital, MA, USA.
METHODS: Subjects with spinal cord injury and documentation of neurogenic bladder were randomized to receive 6 months of cranberry extract tablet or placebo, followed by the alternate preparation for an additional 6 months. The primary outcome was the incidence of UTI.
RESULTS: Forty-seven subjects completed the trial. We found a reduction in the likelihood of UTI and symptoms for any month while receiving the cranberry tablet (P<0.05 for all). During the cranberry period, 6 subjects had 7 UTI, compared with 16 subjects and 21 UTI in the placebo period (P<0.05 for both number of subjects and incidence). The frequency of UTI was reduced to 0.3 UTI per year vs 1.0 UTI per year while receiving placebo. Subjects with a glomerular filtration rate (GFR) greater than 75 ml min(-1) received the most benefit.
CONCLUSION: Cranberry extract tablets should be considered for the prevention of UTI in SCI patients with neurogenic bladder. Patients with a high GFR may receive the most benefit.
Abstract: Cranberry juice (CJ) has biological properties that may provide health benefits. In this study, we investigated the influence of CJ (pH 5.5) on several activities in vitro associated with the development of Streptococcus mutans UA159 biofilms. The ability of CJ to influence the adherence of S. mutans to either saliva- (sHA) or glucan-coated hydroxyapatite (gsHA), and to inhibit the glucan production by purified glucosyltransferases adsorbed to sHA was determined. For the adherence assays, we used both uncoated and saliva-coated bacterial cells. Furthermore, we examined whether CJ interferes with the viability, development, polysaccharide composition and acidogenicity of S. mutans biofilms. A solution containing equivalent amounts of glucose, fructose and organic acids at pH 5.5 was used as negative control. The adherence of S. mutans (uncoated and saliva-coated) to either sHA or gsHA treated with 25% CJ (v/v) was remarkably reduced (40-85% inhibition compared to control: p < 0.05), indicating that CJ effectively blocked the bacterial adherence to binding sites in salivary pellicle and in glucans. In contrast, when the bacterial cells alone were treated with CJ they adhered to the similar untreated surfaces. Cranberry juice (25%, v/v) also inhibited the activities of surface-adsorbed GTF B and C (70-80% inhibition compared to control, p < 0.05). The effect of CJ on the viability of microorganisms in biofilms was not significant. Biofilm formation and accumulation were significantly reduced by topical applications of 25% CJ (v/v) twice daily with 1-min exposures (p < 0.05). The biomass and insoluble glucan content of the biofilms in addition to its acidogenicity were significantly reduced by cranberry treatments (p < 0.05). Our data show that cranberry juice inhibited glucan-mediated biofilm development and acid production, and holds promise as a natural product to prevent biofilm-related oral diseases.
Abstract: Cranberry crude extracts, in various vehicles, have shown inhibitory effects on the formation of oral biofilms in vitro. The presence of proanthocyanidins (PAC) in cranberry extracts has been linked to biological activities against specific virulence attributes of Streptococcus mutans, e.g. the inhibition of glucosyltransferase (Gtf) activity. The aim of the present study was to determine the influence of a highly purified and chemically defined cranberry PAC fraction on S. mutans biofilm formation on saliva-coated hydroxyapatite surface, and on dental caries development in Sprague-Dawley rats. In addition, we examined the ability of specific PAC (ranging from low-molecular-weight monomers and dimers to high-molecular-weight oligomers/polymers) to inhibit GtfB activity and glycolytic pH drop by S. mutans cells, in an attempt to identify specific bioactive compounds. Topical applications (60-second exposure, twice daily) with PAC (1.5 mg/ml) during biofilm formation resulted in less biomass and fewer insoluble polysaccharides than the biofilms treated with vehicle control had (10% ethanol, v/v; p < 0.05). The incidence of smooth-surface caries in rats was significantly reduced by PAC treatment (twice daily), and resulted in less severe carious lesions compared to the vehicle control group (p < 0.05); the animals treated with PAC also showed significantly less caries severity on sulcal surfaces (p < 0.05). Furthermore, specific A-type PAC oligomers (dimers to dodecamers; 0.1 mg/ml) effectively diminished the synthesis of insoluble glucans by GtfB adsorbed on a saliva-coated hydroxyapatite surface, and also affected bacterial glycolysis. Our data show that cranberry PAC reduced the formation of biofilms by S. mutans in vitro and dental caries development in vivo, which may be attributed to the presence of specific bioactive A-type dimers and oligomers.
Abstract: BACKGROUND AND OBJECTIVE: The purpose of this study was to investigate the effects of cranberry polyphenol fraction on biofilm formation and activities of Arg-gingipain and Lys-gingipain in Porphyromonas gingivalis. MATERIAL AND METHODS: The polyphenol fraction was prepared by using a glass column packed with Amberlite XAD 7HP and 70% aqueous ethanol as an elution solvent. RESULTS: Synergistic biofilm formation by P. gingivalis and Fusobacterium nucleatum was significantly inhibited by the polyphenol fraction at a concentration of 250 microg/mL compared with untreated controls (p < 0.01). Arg-gingipain and Lys-gingipain activities in P. gingivalis ATCC 33277 and FDC 381 were inhibited significantly at a polyphenol fraction concentration of > or = 1 microg/mL (p < 0.05). CONCLUSION: These findings indicate that the polyphenol fraction inhibits biofilm formation and the Arg-gingipain and Lys-gingipain activities of P. gingivalis.
Abstract: Cranberry juice is known to inhibit bacterial adhesion. We examined the inhibitory effect of cranberry juice on the adhesion of oral streptococci strains labeled with [3H]-thymidine to saliva-coated hydroxyapatite beads (s-HA). When the bacterial cells were momentarily exposed to cranberry juice, their adherence to s-HA decreased significantly compared with the control (P < 0.01). Their hydrophobicity also decreased dependently with the concentration of cranberry juice. We also evaluated the inhibitory effect of cranberry juice on biofilm formation. By using a microplate system, we found that the high molecular mass constituents of cranberry juice inhibited the biofilm formation of the tested streptococci. The inhibitory activity was related to the reduction of the hydrophobicity. The present findings suggest that cranberry juice component(s) can inhibit colonization by oral streptococci to the tooth surface and can thus slow development of dental plaque.
Abstract: No abstract - Introduction: Urinary tract infections (UTI) are the commonest bacterial infection in older people. Half of all women experience at least one UTI and the risk increases with age. The present management of recurrent urinary tract infection is prophylaxis with low-dose, long-term antibiotics. However, there is a growing reluctance to prescribe antibiotics unless absolutely essential because of fears about antimicrobial resistance. So the recent resurgence in interest in the potential role of cranberry
products is timely.
Abstract: No abstract - Introduction: Cranberry (Vacinicum macrocarpon) is traditionally used in folk medicine for treatment of urinary tract infections. In a recent study, we established that in addition to the antiadhesion effects, concentrated cranberry juice had a direct antimicrobial effect in vitro. We were also able to confirm a direct antimicrobial activity in vitro against a strain of Klebsiella
pneumoniae, in the urine of subjects after ingestion of a commercial cranberry product. While bacteria are the most common cause of urinary tract infections, frequent or prolonged antimicrobial therapy, use of catheters, severely ill patients, high plasma glucose, and invasive procedures can often lead to candiduria. A review of the literature identified one study (Swartz and Medrek 1968), which reported that cranberry juice (40%) in Sabouraud’s dextrose agar had minimal effect on the growth of Candida albicans compared to 0.087% benzoic acid. In this study, we evaluate the anti-Candida activity of urine specimens after ingestion of cranberry.
Abstract: Three proanthocyanidin trimers possessing A-type interflavanoid linkages, epicatechin-(4beta-->6)-epicatechin-(4beta-->8, 2beta-->O-->7)-epicatechin (4), epicatechin-(4beta-->8, 2beta-->O-->7)-epicatechin-(4beta-->8)-epicatechin (5), and epicatechin-(4beta-->8)-epicatechin-(4beta-->8, 2beta-->O-->7)-epicatechin (6), were isolated from the ripe fruits of Vaccinium macrocarpon (cranberry) and prevented adherence of P-fimbriated Escherichia coli isolates from the urinary tract to cellular surfaces containing alpha-Gal(1-->4)beta-Gal receptor sequences similar to those on uroepithelial cells. The structure of 4 was elucidated by a combination of spectroscopic methods and acid-catalyzed degradation with phloroglucinol. Also isolated were the weakly active epicatechin-(4beta-->8, 2beta-->O-->7)-epicatechin (procyanidin A2) (3) and the inactive monomer epicatechin (1) and the inactive dimer epicatechin-(4beta-->8)-epicatechin (procyanidin B2) (2).
Abstract: BACKGROUND: Urinary tract infections (UTIs) are extremely prevalent and despite treatment with antibiotics, reoccurrences are common causing frustration in the patient and the potential for developing antibiotic resistance. The use of cranberry products to prevent UTIs has recently become popular and more clinical studies are needed to explore this use.
OBJECTIVE: This open label pilot study examined the ability of a concentrated cranberry preparation to prevent UTIs in women with a history of recurrent infections.
SUBJECTS: Women between the ages of 25 and 70 years old were included with a history of a minimum of 6 UTIs in the proceeding year.
INTERVENTION: The women took one capsule twice daily for 12 weeks containing 200 mg of a concentrated cranberry extract standardized to 30% phenolics.
DESIGN: A questionnaire was used initially to determine the patient's medical history and they were asked at monthly intervals if any of the information had changed. All of the women in the study had urinalysis within 24h before starting on the study preparation and once a month after that for 4 months. Subjects were followed-up approximately 2 years later.
RESULTS: All 12 subjects participated in the 12-week study and were available for follow up 2 years later. During the study none of the women had a UTI. No adverse events were reported. Two years later, eight of the women who continue to take cranberry, continue to be free from UTIs.
CONCLUSION: A cranberry preparation with a high phenolic content may completely prevent UTIs in women who are subject to recurrent infections.
PMID: 17296290 [PubMed - indexed for MEDLINE]
Abstract: No abstract - Introduction: Urinary tract infection (UTI) is a common childhood infection. In 30–50% of children with UTI the infections occur recurrently, especially in those with vesicoureteral reflux (VUR), resulting in hospitalizations, and long-term health problems, such as renal scars, hypertension, and end-stage renal disease. To reduce the likelihood of recurrent UTI for children with VUR, antibiotics prophylaxis has been regarded as the therapeutic standard for many years. However, the disadvantage of long-term antibiotic therapy is the potential for development of resistant organisms in the host.
Although cranberry juice prophylaxis was found to reduce the frequency of bacteriuria with pyuria in older women, no studies have yet been reported in the literature on children with VUR. The purpose of this study was to examine whether cranberry juice can be substituted for antibiotic prophylaxis in the prevention of UTI in children with VUR.
Abstract: BACKGROUND AND AIM: Cranberry is a fruit that originated in North America, and it has been used by Native Americans for bacterial infections. Recent studies have revealed it to be effective for preventing refractory urinary infections, while also suggesting that it plays a possible role in the eradication of Helicobacter pylori (H. pylori).
METHODS: The H. pylori strains used in the present study were NCTC11637 and 11638. Sugar and organic acid-rich, and polyphenol-rich fractions were obtained from cranberry juice concentrate by Amberlite XAD7HP-column chromatography. The H. pylori growth inhibition was estimated by OD(660) and titration in liquid culture, and by an agar dilution plate method. The shapes of the bacteria were analyzed by scanning electron microscopy.
RESULTS: Cranberry extract suppressed bacterial proliferation in a dose-dependent manner. In the comparison with other juices, polyphenol-rich fruits (cranberries, blueberries, and red grapes) showed similar growth inhibitory activity, whereas polyphenol-poor fruits (oranges, pineapples, apples, and white grapes) did not show any activity. The polyphenol-rich fraction of cranberry maintained the H. pylori-growth inhibitory activity. More bacteria in a coccoid form were observed after culture with cranberry.
CONCLUSION: Cranberry extract inhibited H. pylori proliferation and it is suggested that polyphenols are responsible for this action. The morphological analysis suggested that cranberry induces H. pylori to develop a coccoid form, thereby inhibiting its growth bacteriostatically. Further basic studies to clarify these mechanisms in combination with in vivo studies are needed.
Abstract: The aim of this study was to assess whether regular consumption of cranberry juice results in elevations in urinary salicylate concentrations in persons not taking salicylate drugs. Two groups of healthy female subjects (11/group) matched for age, weight, and height consumed 250 mL of either cranberry juice or a placebo solution three times a day (i.e., 750 mL/day) for 2 weeks. At weekly intervals, salicylic acid and salicyluric acid (the major urinary metabolite of salicylic acid) concentrations were determined in urine by HPLC with electrochemical detection. Concentrations of salicylic acid in plasma were also determined. Consumption of cranberry juice was associated with a marked increase (p < 0.001) of salicyluric and salicylic acids in urine within 1 week of the intervention. After 2 weeks, there was also a small but significant (p < 0.05) increase in salicylic acid in plasma. The regular consumption of cranberry juice results in the increased absorption of salicylic acid, an anti-inflammatory compound that may benefit health.
Abstract: The objective of this study was to evaluate the effects of various berry extracts, with and without clarithromycin on Helicobacter pylori. Resistance to clarithromycin by H. pylori has been reported, leading to interest in alternatives/adjuncts to therapy with clarithromycin. H. pylori American type culture collection (ATCC) strain 49503 was grown, cell suspensions were made in
PBS and diluted 10-fold. One hundred μl of the suspension was then incubated for 18 h with extracts of raspberry, strawberry, cranberry, elderberry, blueberry, bilberry, and OptiBerry R , a blend of the six berries, at 0.25–1% concentrations. Serially diluted cell suspensions were exposed for 1 h to clarithromycin at 15 μg/ml. Ten μl of bacterial samples from the 10–7 dilution tube
were plated and incubated for 18 h and the number of colonies were counted. Growth of H. pylori was confirmed by the CLO R test. All berry extracts significantly (p < 0.05) inhibited H. pylori, compared with controls, and also increased susceptibility of H. pylori to clarithromycin, with OptiBerry R demonstrating maximal effects.
Abstract: Previous clinical research has suggested that the consumption of cranberry products prevents the adhesion of Escherichia coli to uroepithelial cells by causing changes in bacterial fimbriae. Atomic force microscopy was used to probe the adhesion forces between E. coli (nonfimbriated strain HB101 and the P-fimbriated variant HB101pDC1) and a model surface (silicon nitride), to determine the effect of growth in cranberry products on bacterial adhesion. Bacteria were grown in tryptic soy broth supplemented with either light cranberry juice cocktail (L-CJC) or cranberry proanthocyanidins (PACs). Growth of E. coli HB101pDC1 and HB101 in L-CJC or PACs resulted in a decrease in adhesion forces with increasing number of cultures. In a macroscale bacteria-uroepithelial cell adhesion assay a decrease in bacterial attachment was observed for E. coli HB101pDC1 grown in L-CJC or PACs. This effect was reversible because bacteria that were regrown in cranberry-free medium regained their ability to attach to uroepithelial cells, and their adhesion forces reverted to the values observed in the control condition. Exposure to increasing concentrations of L-CJC resulted in a decrease of bacterial attachment to uroepithelial cells for the P-fimbriated strain after L-CJC treatment (27% by weight) and after PACs treatment (345.8 microg/mL). Cranberry products affect the surface properties, such as fimbriae and lipopolysaccharides, and adhesion of fimbriated and nonfimbriated E. coli. The concentration of cranberry products and the number of cultures the bacteria were exposed to cranberry determines how much the adhesion forces and attachment are altered.
Abstract: OBJECTIVES: The aim of this study was to determine whether consumption of sweetened dried cranberries elicits urinary anti-adherence properties against Escherichia coli as previously demonstrated with cranberry juice and/or sweetened cranberry juice cocktail, compared to unsweetened raisins.
DESIGN: Uropathogenic E. coli isolates were obtained from five women with culture-confirmed urinary tract infections (UTIs). Four urine samples were collected from each subject. The first urine sample was collected before any study intervention. The second urine sample was collected 2-5 hours after consumption of one box (42.5 g) of raisins. The third urine sample was collected 5-7 days later. The final urine sample was collected 2-5 hours after consumption of approximately 42.5 g of dried cranberries.
MATERIALS AND METHODS: E. coli isolates were incubated separately in each of the four urine samples collected from the five subjects. Bacteria were harvested from the urine and tested for the ability to prevent adhesion of P-fimbriated E. coli bacteria using a mannose-resistant hemagglutination assay with human red blood cells (A1, Rh+).
RESULTS: Of the urine samples collected after dried cranberry consumption, one demonstrated 50% antiadherence activity, two demonstrated 25% activity, and two did not show any increased activity. None of the control urine samples and none of the postraisin consumption samples demonstrated any inhibitory activity.
CONCLUSIONS: Data from this pilot study on only five subjects suggest that consumption of a single serving of sweetened dried cranberries may elicit bacterial antiadhesion activity in human urine, whereas consumption of a single serving of raisins does not. Further studies are needed to verify the antiadhesion effect of sweetened dried cranberries. In addition, dose-response and pharmacokinetics of the active compounds in the dried cranberries need to be determined. If clinical research is positive, dried cranberries could potentially be a viable alternative to cranberry juice consumption for prevention of UTIs.
Abstract: OBJECTIVES: To compare the effectiveness of cranberry extract with low-dose trimethoprim in the prevention of recurrent urinary tract infections (UTIs) in older women.
PATIENTS AND METHODS: One hundred and thirty-seven women with two or more antibiotic-treated UTIs in the previous 12 months were randomized to receive either 500 mg of cranberry extract or 100 mg of trimethoprim for 6 months.
RESULTS: Thirty-nine of 137 participants (28%) had an antibiotic-treated UTI (25 in the cranberry group and 14 in the trimethoprim group); difference in proportions relative risk 1.616 (95% CI: 0.93, 2.79) P = 0.084. The time to first recurrence of UTI was not significantly different between the groups (P = 0.100). The median time to recurrence of UTI was 84.5 days for the cranberry group and 91 days for the trimethoprim group (U = 166, P = 0.479). There were 17/137 (12%) withdrawals from the study, 6/69 (9%) from the cranberry group and 11/68 (16%) from the trimethoprim group (P = 0.205), with a relative risk of withdrawal from the cranberry group of 0.54 (95% CI: 0.19, 1.37).
CONCLUSIONS: Trimethoprim had a very limited advantage over cranberry extract in the prevention of recurrent UTIs in older women and had more adverse effects. Our findings will allow older women with recurrent UTIs to weigh up with their clinicians the inherent attractions of a cheap, natural product like cranberry extract whose use does not carry the risk of antimicrobial resistance or super-infection with Clostridium difficile or fungi.
Abstract: BACKGROUND: Ingestion of cranberry (Vaccinium macrocarpon Ait.) has traditionally been utilized for prevention of urinary tract infections. The proanthocyanidins (PACs) in cranberry, in particular the A-type linkages have been implicated as important inhibitors of primarily P-fimbriated E. coli adhesion to uroepithelial cells. Additional experiments were required to investigate the persistence in urine samples over a broader time period, to determine the most effective dose per day and to determine if the urinary anti-adhesion effect following cranberry is detected within volunteers of different origins.
METHODS: Two separate bioassays (a mannose-resistant hemagglutination assay and an original new human T24 epithelial cell-line assay) have assessed the ex-vivo urinary bacterial anti-adhesion activity on urines samples collected from 32 volunteers from Japan, Hungary, Spain and France in a randomized, double-blind versus placebo study. An in vivo Caenorhabditis elegans model was used to evaluate the influence of cranberry regimen on the virulence of E. coli strain.
RESULTS: The results indicated a significant bacterial anti-adhesion activity in urine samples collected from volunteers that consumed cranberry powder compared to placebo (p < 0.001). This inhibition was clearly dose-dependent, prolonged (until 24 h with 72 mg of PAC) and increasing with the amount of PAC equivalents consumed in each cranberry powder regimen. An in vivo Caenorhabditis elegans model showed that cranberry acted against bacterial virulence: E. coli strain presented a reduced ability to kill worms after a growth in urines samples of patients who took cranberry capsules. This effect is particularly important with the regimen of 72 mg of PAC.
CONCLUSIONS: Administration of PAC-standardized cranberry powder at dosages containing 72 mg of PAC per day may offer some protection against bacterial adhesion and virulence in the urinary tract. This effect may offer a nyctohemeral protection.
Abstract: Purpose: To describe the incidence of and risk factors for acute cystitis among nondiabetic and diabetic postmenopausal women.
Methods:We conducted a population-based, prospective cohort study of 1017 postmenopausal women, aged 55 to 75 years, who were enrolled in a health maintenance organization and followed for 2 years. A wide range of behavioral and physiologic exposures were assessed at baseline interview and follow-up clinic visits; the main outcome measure was microbiologically confirmed acute symptomatic cystitis. Follow-up was 87% at 12 months and 81% at 24 months.
Results:During 1773 person-years of follow-up, 138 symptomatic urinary tract infections occurred (incidence, 0.07 per person-year). Independent predictors of infection included insulin-treated diabetes (hazard ratio [HR] = 3.4; 95% confidence interval [CI]: 1.7 to 7.0) and a lifetime history of urinary tract infection (HR for six or more infections = 6.9; 95% CI: 3.5 to 13.6). Borderline associations included a history of vaginal estrogen cream use in the last month (HR = 1.8; 95% CI: 1.0 to 3.4), a history of kidney stones (HR = 1.9; 95% CI: 1.0 to 3.7), and asymptomatic bacteriuria at baseline (HR = 1.8; 95% CI: 0.9 to 3.5). Sexual activity, urinary incontinence, parity, postcoital urination, vaginal dryness, use of cranberry juice, vaginal bacterial flora, and postvoid residual bladder volume were not associated with incident acute cystitis after multivariable adjustment.
Conclusion:Insulin-treated diabetes is a potentially modifiable risk factor for incident acute cystitis among postmenopausal women, whereas a lifetime history of urinary tract infection was the strongest predictor. Use of oral or vaginal estrogen was not protective, and a wide range of behavioral and physiologic factors was not associated with acute cystitis episodes in this generally healthy sample.
Abstract: The effect of cranberry juice (CJ) and cranberry proanthocyanidins (PAC) on the infectivity of human enteric virus surrogates, murine norovirus (MNV-1), feline calicivirus (FCV-F9), MS2(ssRNA) bacteriophage, and phiX-174(ssDNA) bacteriophage was studied. Viruses at high (approximately 7 log(10) PFU/ml) or low (approximately 5 log(10) PFU/ml) titers were mixed with equal volumes of CJ, 0.30, 0.60, and 1.20 mg/ml final PAC concentration, or water and incubated for 1 h at room temperature. Viral infectivity after treatments was evaluated using standardized plaque assays. At low viral titers, FCV-F9 was undetectable after exposure to CJ or the three tested PAC solutions. MNV-1 was reduced by 2.06 log(10) PFU/ml with CJ, and 2.63, 2.75, and 2.95 log(10) PFU/ml with 0.15, 0.30, and 0.60 mg/ml PAC, respectively. MS2 titers were reduced by 1.14 log(10) PFU/ml with CJ, and 0.55, 0.80, and 0.96 log(10) PFU/ml with 0.15, 0.30, and 0.60 mg/ml PAC, respectively. phi-X174 titers were reduced by 1.79 log(10) PFU/ml with CJ, and 1.95, 3.67, and 4.98 log(10) PFU/ml with PAC at 0.15, 0.30, and 0.60 mg/ml, respectively. Experiments using high titers showed similar trends but with decreased effects. CJ and PAC show promise as natural antivirals that could potentially be exploited for foodborne viral illness treatment and prevention.
Abstract: No abstract - Introduction: Urinary tract infections (UTIs) account for more than 11 million physician visits annually in the United States and have become increasingly resistant to first-line antibiotic therapy. Recent evidence suggests that consumption of cranberry juice beverages is effective at preventing UTIs, although further studies are needed to validate potential treatment effects. While early research focused on a mechanism of urinary acidification, the largest clinical trial to date found no evidence to support this. Recent studies suggest that cranberry proanthocyanidins (condensed tannins) may inhibit P-fimbriated Escherichia coli from adhering to uroepithelial cells, the initial step in development of UTI. The effectiveness of cranberry proanthocyanidins and cranberry beverages against antibiotic-resistant E coli, however, has not been previously tested. We assessed whether consumption of cranberry juice cocktail prevents adhesion of antibiotic-resistant uropathogenic P-fimbriated E coli to the uroepithelium.
Abstract: BACKGROUND: The cranberry produces antimicrobial compounds such as proanthocyanidines in response to microbial invasion. In vitro it is able to prevent growth, adhesion or biofilm formation of a large number of bacteria, while clinically, cranberry juice has been shown to prevent urinary tract infections (UTI) in women. However, the effect of cranberry on bacterial colonization more widely has not been evaluated. We were interested in studying cranberry juice in children since many children with recurrent UTI need long-term antimicrobial prophylaxis and would benefit from an alternative. OBJECTIVE: To evaluate the effect of cranberry juice on nasopharyngeal and colonic bacterial flora, to evaluate how well cranberry juice is accepted by children and to evaluate its effect on infectious diseases and related symptoms. DESIGN: Children (mean age 4.3 years) in day care centers were randomized to receive either cranberry juice (n=171) or a placebo (n=170) for 3 months. Bacterial samples were collected before and after the intervention and analyzed for both respiratory bacterial pathogens and enteric fatty acid composition, reflecting changes in the colonic bacterial flora. Infectious diseases and their symptoms were monitored using symptom diaries. Compliance was evaluated as the number of drop-outs during the trial and by counting the numbers of doses taken. RESULTS: The carriage of respiratory bacteria did not change significantly during the intervention, while fecal fatty acid composition changed significantly with time (P<0.001) but did not differ between the groups (P>0.05). Cranberry juice had no effect on common infectious diseases or their symptoms. The cranberry juice was well accepted: the number of drop-outs in 3 months was 18 (11%) in the cranberry group and 11 (7%) in the placebo group, and most of the doses were taken as instructed, 145 (88%) and 129 (77%) children, respectively, taking at least 90% of the doses. CONCLUSIONS: Cranberry juice was well accepted by the children, but led to no change in either the bacterial flora in the nasopharynx or the bacterial fatty acid composition of stools. Thus cranberries seem to have beneficial effect on urinary health only and this is not compromised by other unexpected antimicrobial effects.
Abstract: Background: cranberry juice is often given to older people in hospital to prevent urinary tract infection (UTI), although
there is little evidence to support its use.
Objective: to assess whether cranberry juice ingestion is effective in reducing UTIs in older people in hospital.
Design: randomised, placebo-controlled, double-blind trial.
Setting: Medicine for the Elderly assessment and rehabilitation hospital wards.
Subjects: 376 older patients in hospital.
Methods: participants were randomised to daily ingestion of 300 ml of cranberry juice or matching placebo beverage. The primary outcome was time to onset of first UTI. Secondary outcomes were adherence to beverage drinking, courses of antibiotics prescribed, and organisms responsible for UTIs.
Results: a total of 21/376 (5.6%) participants developed a symptomatic UTI: 14/189 in the placebo group and 7/187 in the cranberry juice group. These between-group differences were not significant, relative risk (RR) 0.51 [95% CI 0.21–1.22, P = 0.122). Although there were significantly fewer infections with Escherichia coli in the cranberry group (13 versus 4) RR 0.31 [95% CI 0.10–0.94, P =0.027], this should be interpreted with caution as it was a secondary outcome.
Conclusion: despite having the largest sample size of any clinical trial yet to have examined the effect of cranberry juice ingestion, the actual infection rate observed was lower than anticipated, making the study underpowered. This study has confirmed the acceptability of cranberry juice to older people. Larger trials are now required to determine whether it is effective in reducing UTIs in older hospital patients.
Abstract: The purpose of this study was to investigate the effect of cranberry polyphenol fraction on mutans streptococci. Hydrophobicity is an important factor in the adherence of bacteria to the tooth surface. We found that cranberry polyphenol fraction significantly decreased the hydrophobicity of Streptococcus sobrinus 6715, Streptococcus mutans MT8148R and JC2 in a dose-dependent manner (p<0.05). Biofilm formation by S. sobrinus 6715 and S. mutans MT8148R was inhibited by 100 microg/ml cranberry polyphenol fraction (p<0.01). When dosage was increased to 500 microg/ml, biofilm formation by S. mutans JC2 was significantly inhibited (p<0.05). Addition of 500 microg/ml cranberry polyphenol fraction to medium inhibited growth of S. mutans MT8148R compared with the control (p<0.05).
Abstract: OBJECTIVE: Probiotics and cranberry have been shown to inhibit Helicobacter pylori in vitro owing to bacteriocin production and high levels of proanthocyanidins, respectively. These effects have been confirmed in clinical trials with H. pylori-positive subjects. The aim of this study was to evaluate whether regular intake of cranberry juice and the probiotic Lactobacillus johnsonii La1 (La1) may result in an additive or synergistic inhibition of H. pylori in colonized children.METHODS: A multicentric, randomized, controlled, double-blind trial was carried out in 295 asymptomatic children (6-16 y of age) who tested positive for H. pylori by (13)C-urea breath test (UBT). Subjects were allocated in four groups: cranberry juice/La1 (CB/La1), placebo juice/La1 (La1), cranberry juice/heat-killed La1 (CB), and placebo juice/heat-killed La1 (control). Cranberry juice (200 mL) and La1 product (80 mL) were given daily for 3 wk, after which a second UBT was carried out. A third UBT was done after a 1-mo washout in those children who tested negative in the second UBT.RESULTS: Two hundred seventy-one children completed the treatment period (dropout 8.1%). Helicobacter pylori eradication rates significantly differed in the four groups: 1.5% in the control group compared with 14.9%, 16.9%, and 22.9% in the La1, CB, and CB/La1 groups, respectively (P < 0.01); the latter group showed a slight but not significant increase when compared with the other treated groups. The third UBT was carried out only in 19 of the 38 children who tested negative in the second UBT and H. pylori was detected in 80% of them.CONCLUSION: These results suggest that regular intake of cranberry juice or La1 may be useful in the management of asymptomatic children colonized by H. pylori; however, no synergistic inhibitory effects on H. pylori colonization were observed when both foodstuffs were simultaneously consumed.
Abstract: OBJECTIVE: To determine whether recurrences of urinary tract infection can be prevented with cranberry-lingonberry juice or with Lactobacillus GG drink. Design: Open, randomised controlled 12 month follow up trial.
SETTING: Health centres for university students and staff of university hospital.
PARTICIPANTS: 150 women with urinary tract infection caused by Escherichia coli randomly allocated into three groups. Interventions: 50 ml of cranberry-lingonberry juice concentrate daily for six months or 100 ml of lactobacillus drink five days a week for one year, or no intervention. Main outcome measure: First recurrence of symptomatic urinary tract infection, defined as bacterial growth >/=10(5 )colony forming units/ml in a clean voided midstream urine specimen.
RESULTS: The cumulative rate of first recurrence of urinary tract infection during the 12 month follow up differed significantly between the groups (P=0.048). At six months, eight (16%) women in the cranberry group, 19 (39%) in the lactobacillus group, and 18 (36%) in the control group had had at least one recurrence. This is a 20% reduction in absolute risk in the cranberry group compared with the control group (95% confidence interval 3% to 36%, P=0.023, number needed to treat=5, 95% confidence interval 3 to 34).
CONCLUSION: Regular drinking of cranberry juice but not lactobacillus seems to reduce the recurrence of urinary tract infection.
Abstract: To determine the efficacy of the consumption of cranberry juice versus placebo with regard to the presence of in vitro bacterial anti-adherence activity in the urine of healthy volunteers. Twenty healthy volunteers, 10 men and 10 women, were included. The study was a double-blind, randomized, placebo-controlled, and cross-over study. In addition to normal diet, each volunteer received at dinner a single dose of 750 ml of a total drink composed of: (1) 250 ml of the placebo and 500 ml of mineral water, or (2) 750 ml of the placebo, or (3) 250 ml of the cranberry juice and 500 ml of mineral water, or (4) 750 ml of the cranberry juice. Each volunteer took the four regimens successively in a randomly order, with a washout period of at least 6 days between every change in regimen. The first urine of the morning following cranberry or placebo consumption was collected and used to support bacterial growth. Six uropathogenic Escherichia coli strains (all expressing type 1 pili; three positive for the gene marker for P-fimbriae papC and three negative for papC), previously isolated from patients with symptomatic urinary tract infections, were grown in urine samples and tested for their ability to adhere to the T24 bladder cell line in vitro. There were no significant differences in the pH or specific gravity between the urine samples collected after cranberry or placebo consumption. We observed a dose dependent significant decrease in bacterial adherence associated with cranberry consumption. Adherence inhibition was observed independently from the presence of genes encoding type P pili and antibiotic resistance phenotypes. Cranberry juice consumption provides significant anti-adherence activity against different E. coli uropathogenic strains in the urine compared with placebo.
Abstract: STUDY DESIGN: Literature review. OBJECTIVES: Urinary tract infections (UTIs) are the most common medical complication experienced by individuals with spinal cord injury (SCI). Recent research presents conflicting evidence regarding use of cranberry in reducing growth and colonization of uroepithelial cells by uropathogenic bacteria. The objective was to determine whether the literature supports the use of cranberry in preventing or treating UTIs in the SCI population. METHODS: MEDLINE was searched for intervention studies, which investigated the use of cranberry in the prevention or treatment of UTIs in the SCI population. If the studies met the inclusion criteria, full articles were located and reviewed. RESULTS: Five studies (four randomized clinical control-three trials using cranberry tablets vs placebos and one using cranberry juice-and one pilot study using cranberry juice) were identified which evaluated the effectiveness of cranberry products for the prevention or treatment of UTIs in the SCI population. Three studies reported no statistically significant effect of cranberry tablets in urinary pH, urinary bacterial count, urinary white blood cell (WBC) count, urinary bacterial, and WBC counts in combination or episodes of symptomatic UTIs. A fourth study showed that cranberry juice intake significantly reduced biofilm load compared with baseline. A final study reported fewer UTIs during the period with cranberry extract tablets vs placebo. CONCLUSIONS: Limited evidence from clinical trials that vary in design suggests that cranberry, in juice or supplement form, does not seem to be effective in preventing or treating UTIs in the SCI population. More rigorous clinical research is needed to confirm this.
Abstract: No abstract - Conclusion:
Science often causes us to disregard the validity of folklore
treatments for common medical conditions. However,
those folklore practices that retain a persistent consumer
and practitioner following over time merit rigorous scientific scrutiny. Approaches such as those described here
regarding UTI risk reduction by cranberry juice could serve
as a model to clarify the potential functional food role of
Cranberry juice in treating and preventing UTIs.
Abstract: Cranberry juice (Vaccinium macrocarpon) is a widely used and recommended North-American folk remedy for prophylaxis of urinary tract infections (UTI). Clinical trials have documented its efficacy in women with recurrent UTI, but so far not in other groups of patients. The composition of effective cranberry products and its dosage in UTI prophylaxis have not been defined. Intriguing experimental research has identified an anti-adhesive mechanism of cranberry juice that prevents docking of bacteria on host tissues. This efficacy mechanism can be traced in patients' urine following oral intake of cranberry products and appears to be due to proanthocyanidins with an A-type linkage of flavanols. The application of this anti-adhesion mechanism of cranberry-proanthocyandins is currently also investigated in other common diseases of bacterial pathogenesis, for example Helicobacter pylori-associated gastritis and dental caries/periodontal disease. The use of cranberry products appears to be safe and provide additional benefits by anti-oxidant and cholesterol-lowering activity.
Abstract: We explore the anti-microbial activity of urine specimens after the ingestion of a commercial cranberry preparation. Twenty subjects without urinary infection, off antibiotics and all supplements or vitamins were recruited. The study was conducted in two phases: in phase 1, subjects collected the first morning urine prior to ingesting 900mg of cranberry and then at 2, 4 and 6 h. In phase 2, subjects collected urine on 2 consecutive days: on Day 1 no cranberry was ingested (control specimens), on Day 2, cranberry was ingested. The pH of all urine specimens
were adjusted to the same pH as that of the first morning urine specimen. Aliquots of each specimen were independently inoculated with Escherichia coli, Klebsiella pneumoniae or Candida albicans. After incubation, colony forming units/ml (CFU ml 1) in the control specimen
was compared with CFU ml 1 in specimens collected 2, 4 and 6 h later. Specimens showing 50% reduction in CFU ml 1 were considered as having ‘activity’ against the strains tested. In phase 1, 7/20 (35%) subjects had anti-microbial activity against E. coli, 13/20 (65%) against K. pneumoniae and 9/20 (45%) against C. albicans in specimens collected 2–6 h after ingestion of cranberry. In phase 2, 6/9 (67%) of the subjects had activity against K. pneumoniae. This pilot
study demonstrates weak anti-microbial activity in urine specimens after ingestion of a single dose of commercial cranberry. Anti-microbial activity was noted only against K. pneumoniae 2–6 h after ingestion of the cranberry preparation.
Abstract: Studies were performed to investigate the effect of several cranberry and grape juice extracts on the inhibition of reovirus infectivity following cell culture inoculation. Infectivity testing was performed utilizing cranberry juice extracts NutriCran-100TM and NutriCran-90TM. At 5% extract concentrations, titers were reduced by ca. 50%. Cranberry cocktail juice caused an infectivity loss of ca. 10%. We ascribe these data to higher concentrations of proanthocyanidins (PACs) in the cranberry extracts.
Further testing was performed utilizing purified high and low molecular weight cranberry PAC fractions (CB HMW and CB LMW, respectively), a cranberry flavonol glycoside (CB EToAc), cranberry anthocyanins (CB CA), and a grape PAC extract. Reovirus titers were reduced to undetectable levels at PAC concentrations f0.2%. CB CA had no effect on the inhibition of infectivity titers. Loss of infectivity titers was in the order: GP PACACB HMWACB LMWACB EToAc. Probe homogenization of CB HMWenhanced the extract to efficacy levels equal to that of grape PAC. Reovirus dsRNA segments were undetectable 96-h postcranberry cocktail juice pretreatment of MA-104 cell cultures. This study indicates an inhibition of reovirus infectivity titers by cranberry or grape juices or their purified PAC extracts. Viral inhibition probably occurs at the host cell surface.
Abstract: Periodontitis is a chronic inflammatory disease that affects the tooth supporting tissues. Gingival fibroblasts are the most abundant cells in periodontal tissues and participate actively in the host inflammatory response to periodontopathogens, which is known to mediate local tissue destruction in periodontitis. The aim of this study was to investigate the effect of a proanthocyanidin-enriched cranberry fraction, prepared from cranberry juice concentrate, on inflammatory mediator production by gingival fibroblasts stimulated by the lipopolysaccharide (LPS) of Aggregatibacter actinomycetemcomitans. Interleukin (IL)-6, IL-8, and prostaglandin E(2) (PGE(2)) production by fibroblasts treated with the cranberry fraction and stimulated by A. actinomycetemcomitans LPS was evaluated by enzyme-linked immunosorbent assay. Changes induced by A. actinomycetemcomitans LPS and the cranberry fraction in the expression and phosphorylation state of fibroblast intracellular signaling proteins were characterized by antibody microarrays. The LPS-induced IL-6, IL-8, and PGE(2) responses of gingival fibroblasts were inhibited by treatment with the cranberry fraction. This fraction was found to inhibit fibroblast intracellular signaling proteins, a phenomenon that may lead to a down-regulation of activating protein-1 activity. Cranberry components also reduced cyclooxygenase 2 expression. This study suggests that cranberry juice contains molecules with interesting properties for the development of new host-modulating therapeutic strategies in the adjunctive treatment of periodontitis.
Abstract: We investigated the antimicrobial effect of constituents of the American cranberry (Vaccinium macrocarpon); sugar plus organic acids, phenolics, and anthocyanins, against Escherichia coli O157:H7. Each fractional component was assayed over a 24-h period with 5-log initial inocula to determine the minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), and log CFU/ml reductions, at their native pH and neutral pH. Each fraction produced significant reductions (P<0.05) at the native pH: MICs for sugars plus organic, phenolics, and anthocyanins were 5.6/2.6 Brix/acid (citric acid equivalents) 2.70g/L (gallic acid equivalent), and 14.80mg/L (cyanidin-3-glucoside equivalent), respectively. Sugars plus organic acids at native pH (3) produced a reduction below detectable limits (<1 log CFU/ml) compared to the control at 24h for 11.3/5.2 and 5.6/2.6 Brix/acid. Phenolics at native pH (4) produced reductions below detectable limits compared to the control at 24h and initial inocula for treatments of 5.40 and 2.70g/L. Anthocyanins at native pH (2) produced reductions below detectable limits for treatments of 29.15 and 14.80mg/L cyanidin-3-glucoside equivalents. Neutralized phenolics and anthocyanins had the same MIC and MBC as those at their native pH. Neutralized sugars plus organic acids did not inhibit bacterial growth compared to the control. Neutralized phenolics reduced bacteria below detectable limits in treatments of 5.40g/L and 2.70g/L compared to the control. Neutralized anthocyanins reduced bacterial growth below detectable limits at the concentration of 29.15mg/L, but at 14.80mg/L there was no significant reduction. Stationary-phase cells of E. coli O157:H7 were treated with 5% of each fraction in 0.8% NaCl for 20min and viewed under transmission electron microscopy. All fractions caused significant damage compared the control. Sugars plus organic acids caused visible osmotic stress, while phenolics and anthocyanins caused disintegration of the outer membrane.