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Urinary Tract Health and Antibacterial Benefits

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The Cranberry Extract Oximacro Exerts in vitro Virucidal Activity Against Influenza Virus by Interfering With Hemagglutinin.

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Authors
Luganini A; Terlizzi ME; Catucci G; Gilardi G; Maffei ME; Gribaudo G.
Journal
Frontiers in Microbiology. 9:1826,
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.

The Effect of Cranberry Juice Consumption on the Recurrence of Urinary Tract Infection: Relationship to Baseline Risk Factors.

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Authors
Maki, K. C. Nieman, K. M. Schild, A. L. Kaspar, K. L. Khoo, C.
Journal
Journal of the American College of Nutrition;37(2):121-126.
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 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 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.

The Effect of Sweetened Dried Cranberry Consumption on Urinary Proteome and Fecal Microbiome in Healthy Human Subjects.

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Authors
Bekiares N; Krueger CG; Meudt JJ; Shanmuganayagam D; Reed JD.
Journal
Omics a Journal of Integrative Biology. 22(2):145-153
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.

The Effects of Training and the Use of Cranberry Capsule in Preventing Urinary Tract Infections After Urostomy.

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Authors
Temiz Z; Cavdar I.
Journal
Complementary Therapies in Clinical Practice. 31:111-117
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.

The Hospital-Acquired Conditions (HAC) Reduction Program: Using Cranberry Treatment to Reduce Catheter-Associated Urinary Tract Infections and Avoid Medicare Payment Reduction Penalties.

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Authors
Saitone TL; Sexton RJ; Sexton Ward A.
Journal
Journal of Medical Economics. 21(1):97-106
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.

The Influence of Dietary Supplementation with Cranberry Tablets on the Urinary Risk Factors for Nephrolithiasis.

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Authors
Redmond EJ; Murphy CF; Leonard J; Faulds K; Abdelfadil S; Crowley VE; Lynch TH; Manecksha RP.
Journal
World J Urol, 10.1007/s00345-018-2344-1 [doi]
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.

Cranberry for Urinary Tract Infection: From Bench to Bedside.

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Authors
Nabavi SF; Sureda A; Daglia M; Izadi M; Nabavi SM.
Journal
Current Topics in Medicinal Chemistry. 17(3):331-339
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.

Cranberry Reduces the Risk of Urinary Tract Infection Recurrence in Otherwise Healthy Women: A Systematic Review and Meta-Analysis.

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Authors
Fu Z, Liska D, Talan D, Chung M
Journal
Journal of Nutrition. 147(12):2282-2288
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 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.

Does Cranberry Have a Role in Catheter-Associated Urinary Tract Infections?

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Authors
Thomas D; Rutman M; Cooper K; Abrams A; Finkelstein J; Chughtai B.
Journal
Canadian Urological Association Journal. 11(11):E421-E424
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.

Effectiveness of Dietary Supplements in Spinal Cord Injury Subjects.

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Authors
Navarrete-Opazo A; Cuitino P; Salas I.
Journal
Disability & Health Journal. 10(2):183-197
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.