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Urinary Tract Health and Antibacterial Benefits

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

Posted
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.

Posted
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."

Consumption of sweetened, dried cranberries may reduce urinary tract infection incidence in susceptible women--a modified observational study.

Posted
Authors
Burleigh AE, Benck SM, McAchran SE, Reed JD, Krueger CG, Hopkins WJ
Journal
Nutr J 12(1):139
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.

Cranberries and their bioactive constituents in human health.

Posted
Authors
Blumberg JB, Camesano TA, Cassidy A, Kris-Etherton P, Howell A, Manach C, Ostertag LM, Sies H, Skulas-Ray A, Vita JA
Journal
Adv Nutr 4(6):618-32
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.

Current clinical status on the preventive effects of cranberry consumption against urinary tract infections. [Review]

Posted
Authors
Vasileiou I, Katsargyris A, Theocharis S, Giaginis C
Journal
Nutr Res 33(8):595-607
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.

Cysticlean a highly pac standardized content in the prevention of recurrent urinary tract infections: an observational, prospective cohort study.

Posted
Authors
Sanchez Ballester F, Ruiz Vidal V, Lopez Alcina E, Domenech Perez C, Escudero Fontano E, Oltra Benavent A, Montoliu Garcia A, Sobron Bustamante M
Journal
BMC Urol 13:28
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 (P0.0001), 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 (P0.001). 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.

Quantifying and characterizing proanthocyanidins in cranberries in relation to urinary tract health. [Review]

Posted
Authors
Krueger CG, Reed JD, Feliciano RP Howell AB
Journal
Anal Bioanal Chem 405(13):4385-95
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.

Urine post equivalent daily cranberry juice consumption may opsonize uropathogenicity of Escherichia coli.

Posted
Authors
Chen CS, Ho DR, Chang PJ, Lin WY, Huang YC
Journal
J Infect Chemother 19(5):812-7
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.

Cranberries and Their Bioactive Constituents in Human Health

Posted
Authors
Jeffrey B. Blumberg, Terri A. Camesano, Aedin Cassidy, Penny Kris-Etherton, Amy Howell, Claudine Manach, Luisa M. Ostertag, Helmut Sies, Ann Skulas-Ray, and Joseph A. Vita
Journal
Adv. Nutr. 4: 618–632, 2013
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.