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Cranberries for preventing urinary tract infections - 2012

Posted
Authors
Jepson RG, Williams G, Craig JC.
Journal
Cochrane Database Syst Rev doi: 10.1002/14651858.CD001321.pub5.
Abstract

BACKGROUND:
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.
OBJECTIVES:
To assess the effectiveness of cranberry products in preventing UTIs in susceptible populations.
SEARCH METHODS:
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
SELECTION CRITERIA:
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.
MAIN RESULTS:
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.
AUTHORS' CONCLUSIONS:
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.

Cranberry and recurrent cystitis: more than marketing?.

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Authors
Micali S, Isgro G, Bianchi G, Miceli N, Calapai G, Navarra M
Journal
Crit Rev Food Sci Nutr 54(8):1063-75
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.

Cranberry-derived proanthocyanidins prevent formation of Candida albicans biofilms in artificial urine through biofilm- and adherence-specific mechanisms.

Posted
Authors
Rane HS, Bernardo SM, Howell AB, Lee SA
Journal
J Antimicrob Chemother 69(2):428-36
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.

Effectiveness of cranberry capsules to prevent urinary tract infections in vulnerable older persons: a double-blind randomized placebo-controlled trial in long-term care facilities.

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Authors
Caljouw MAA, Hout WB van den, Putter H, Achterberg WP, Cools HJM, Gussekloo J
Journal
J Am Geriatr Soc 62(1):103-10
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.

Evaluating the binding of selected biomolecules to cranberry derived proanthocyanidins using the quartz crystal microbalance.

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Authors
Weckman NE, Olsson AL, Tufenkji N
Journal
Biomacromolecules 15(4):1375-81
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.

Exploring the role of cranberry polyphenols in periodontits: A brief review.

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Authors
Mukherjee M, Bandyopadhyay P, Kundu D
Journal
J Indian Soc Periodontol 18(2):136-9
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.

Prevention of urinary tract infections with Vaccinium products.

Posted
Authors
Davidson E, Zimmermann BF, Jungfer E, Chrubasik-Hausmann S
Journal
Phytother Res 28(3):465-70
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.

Ratio of "A-type" to "B-type" proanthocyanidin interflavan bonds affects extra-intestinal pathogenic Escherichia coli invasion of gut epithelial cells.

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Authors
Feliciano RP, Meudt JJ, Shanmuganayagam D, Krueger CG, Reed JD
Journal
J Agric Food Chem 62(18):3919-25
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.

Recurrent urinary tract infections among women: comparative effectiveness of 5 prevention and management strategies using a Markov chain Monte Carlo model.

Posted
Authors
Eells SJ, Bharadwa K, McKinnell JA, Miller LG
Journal
Clin Infect Dis 58(2):147-60
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.

Solidago, orthosiphon, birch and cranberry extracts can decrease microbial colonization and biofilm development in indwelling urinary catheter: a microbiologic and ultrastructural pilot study.

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Authors
Cai T, Caola I, Tessarolo F, Piccoli F, D'Elia C, Caciagli P, Nollo G, Malossini G, Nesi G, Mazzoli S, Bartoletti R
Journal
World J Urol 32(4):1007-14
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."