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Urinary Tract Health and Antibacterial Benefits: Human

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A Multicenter, Randomized, Placebo-Controlled Study Evaluating the Efficacy of a Combination of Propolis and Cranberry (Vaccinium macrocarpon) (DUAB) in Preventing Low Urinary Tract Infection Recurrence in Women Complaining of Recurrent Cystitis.

Posted: 
March 20, 2020
Authors: 
Bruyere F; Azzouzi AR; Lavigne JP; Droupy S; Coloby P; Game X; Karsenty G; Issartel B; Ruffion A; Misrai V; Sotto A; Allaert FA.
Journal: 
Urologia Internationalis. 103(1):41-48
Abstract: 

OBJECTIVES: The purpose of the study was to compare the efficacy of a product containing cranberry and propolis (DUAB) to placebo for reducing frequency of cystitis in women with recurrent acute cystitis.METHOD: A multicenter, placebo-controlled, randomized study of women aged >18 years with at least 4 episodes of cystitis in the previous 12 months was performed. The number of cystitis episodes over a 6-month follow-up was the primary end point.RESULTS: Forty-two women were included in the cranberry + propolis group, and 43 women were in the placebo group. The mean age was 53 +/- 18 years, with 6.2 +/- 3.6 cystitis episodes in the previous year, with no differences between the 2 groups. The mean number of infections was lower in the propolis + cranberry group (respectively, 2.3 +/- 1.8 vs. 3.1 +/- 1.8). The total number of cystitis episodes in the first 3 months was lower in the propolis + cranberry group (0.7 +/- 1.1 vs. 1.3 +/- 1.1, p = 0.0257) after adjusting for water consumption. The mean time to onset of the first urinary tract infection (UTI) was also significantly longer in the propolis + cranberry group (69.9 +/- 45.8 days vs. 43.3 +/- 45.9, p = 0.0258). Tolerance to the treatments was good and comparable in both groups.CONCLUSIONS: We demonstrate for the first time that cranberry and propolis supplementation significantly reduces the incidence of UTIs during the first 3 months and delays the onset of an episode of cystitis.

Cranberry, D-mannose and Anti-inflammatory Agents Prevent Lower Urinary Tract Symptoms in Women Undergoing Prolapse Surgery.

Posted: 
March 20, 2020
Authors: 
Russo E; Montt Guevara M; Giannini A; Mannella P; Palla G; Caretto M; Pancetti F; Genazzani AD; Simoncini T.
Journal: 
Climacteric. 1-5, 2019 Nov 01.
Abstract: 

Objective: We assessed the effect on lower urinary tract symptoms (LUTS) of a supplement containing cranberry, D-mannose and anti-inflammatory molecules in postmenopausal women undergoing surgery for cystocele.Study design: Forty postmenopausal women were randomized 1:1 to an active group receiving the nutritional supplement twice a day for 2 weeks starting from surgery, or to a control group receiving surgery only. Primary outcomes were the effectiveness in the postoperative LUTS and urinary tract infections (UTI). LUTS were investigated by a validated questionnaire (ICIQ-FLUTS) at baseline and at week 4. Secondary outcomes were the safety and tolerability of the supplement and other perioperative outcomes.Results: No significant differences were found in perioperative outcomes and in incidence of UTI. After surgery, women treated with the supplement experienced significantly better scores on the filling domain of the questionnaire. A non-significant decrease in voiding scores was also found. No adverse events were detected.Conclusion: The use of an oral supplement containing cranberry, D-mannose and anti-inflammatory molecules decreases the perception of LUTS in postmenopausal women after anterior colporraphy. Our data suggest that perioperative use of nutritional supplements may be useful in the management of postoperative LUTS.

Probiotic and Cranberry Supplementation for Preventing Recurrent Uncomplicated Urinary Tract Infections in Premenopausal Women: A Controlled Pilot Study.

Posted: 
March 20, 2020
Authors: 
Parshottam Koradia; Shital Kapadia; Yamini Trivedi; Gajendrasinh Chanchu; Harper, A.
Journal: 
Expert Review of Anti-Infective Therapy; 2019. 17(9):733-740.
Abstract: 

Objectives: To assess efficacy and safety of Bio-Kult Pro-Cyan (BKPro-Cyan), a product containing two strains of Lactobacilli plus cranberry extract, for preventing recurrent UTIs in pre-menopausal adult women. Methods: This was a randomized, double-blind, placebo-controlled pilot study. Subjects received BKPro-Cyan or placebo twice-daily for 26 weeks. The primary endpoint was the proportion of subjects with recurrent UTI at the end of the study. Results: 115 subjects were screened; 90 were enrolled; 81 completed the study. After 26 weeks, a significantly lower number of women experienced recurrent UTIs with BKPro-Cyan compared to placebo (9.1 vs 33.3%; P=0.0053). BKPro-Cyan produced statistically significant improvements compared to placebo for multiple secondary endpoints, including: greater number of subjects who experienced no UTIs (90 vs 67%; P<0.05); longer time to first UTI (174 vs 90 days; P=0.001); shorter duration of active UTI (5 vs 12 days; P=0.009); Fewer subjects requiring antibiotics (3 vs 11; P<0.05); and shorter median duration of antibiotic treatment (4 vs 7 days; P=0.09). Conclusions: BKPro-Cyan was safe and effective for preventing recurrent UTI in pre-menopausal adult women. These findings support the need for further well-designed trials to clarify the benefits that may be achieved.

Profiling Vaccinium Macrocarpon Components and Metabolites in Human Urine and the Urine Ex-Vivo Effect on Candida Albicans Adhesion and Biofilm-Formation.

Posted: 
March 16, 2020
Authors: 
Baron G; Altomare A; Regazzoni L; Fumagalli L; Artasensi A; Borghi E; Ottaviano E; Del Bo C; Riso P; Allegrini P; Petrangolini G; Morazzoni P; Riva A; Arnoldi L; Carini M; Aldini G.
Journal: 
Biochemical Pharmacology. 113726, 2019 Nov 26.
Abstract: 

The aim of this work was to profile, by using an HPLC-MS/MS method, cranberry compounds and metabolites found in human urine after ingestion of a highly standardized cranberry extract (Anthocran R). Two different strategies were adopted for the data analysis: a targeted and an untargeted approach. These strategies allowed the identification of 42 analytes including cranberry components, known metabolites and metabolites hitherto unreported in the literature, including six valerolactones/valeric acid derivatives whose presence in urine after cranberry consumption has never been described before. Absolute concentrations of 26 over 42 metabolites were obtained by using pure available standards. Urine collected at different time points after the last dosage of Anthocran R were tested on the reference strain C. albicans SC5314, a biofilm-forming strain. Fractions collected after 12 h were found to significantly reduce the adhesion and biofilm formation compared to the control (p < 0.05). A similar effect was then obtained by using Anthocran TM Phytosome TM, the lecithin formulation containing 1/3 of standardized cranberry extract and formulated to enhance the absorption of the cranberry components. The urinary profile of cranberry components and metabolites in the urine fractions collected at 1 h, 6 h and 12 h after the last capsule intake were then reproduced by using the pure standards at the concentration ranges found in the urine fraction, and tested on C. albicans. Only the mixture mimicking the urinary fraction collected at 12 h and containing as main components, quercetin and 5-(3',4'-dihydroxyphenyl)-gamma-valerolactone was found effective thus confirming the ex-vivo results.

Influence of Cranberry Extract on Tamm-Horsfall Protein in Human Urine and its AntiadhesiveActivity Against Uropathogenic Escherichia Coli.

Posted: 
February 19, 2019
Authors: 
Scharf B, Sendker J, Dobrindt U, Hensel A.
Journal: 
Planta Med. 2019 Jan;85(2):126-138. doi: 10.1055/a-0755-7801
Abstract: 

LC-MS characterized cranberry extract from the fruits of Vaccinium macrocarpon inhibited under in vitro conditions the bacterial adhesion of Escherichia coli strain 2980 uropathogenic E. coli (UPEC strains UTI89, NU14) to T24 bladder cells and adhesion of UPEC strain CFT073 to A498 kidney cells in a concentration-dependent manner. Within a biomedical study, urine samples from 16 volunteers (8 male, 8 female) consuming cranberry extract for 7 d (900 mg/d) were analyzed for potential antiadhesive activity against UPEC by ex vivo experiments. Results indicated inhibition of adhesion of UPEC strain UTI89 to human T24 bladder cells. Subgroup analysis proved significant inhibition of bacterial adhesion in case of urine samples obtained from male volunteers while female urine did not influence the bacterial attachment. Differences between antiadhesive capacity of urine samples from male/female volunteers were significant. Protein analysis of the urinesamples indicated increased amounts of Tamm-Horsfall protein (THP, syn. uromodulin) in the active samples. Inhibition of bacterial adhesion by the urine samples was correlated to the respective amount of THP. As it is known that THP, a highly mannosylated glycoprotein, strongly interacts with FimH of UPEC, this will lead to a decreased interaction with uroplakin, a FimH-binding transmembrane protein of urothelial lining cells. From these data it can be concluded that the antiadhesive effect of cranberry after oral intake is not only related to the direct inhibition of bacterial adhesins by extract compounds but is additionally due to an induction of antiadhesive THP in the kidney.

Cranberry Supplementation Does Not Reduce Urinary Tract Infections in Patients With Indwelling Catheters After Pelvic Reconstructive Surgery.

Posted: 
September 4, 2018
Authors: 
Shatkin-Margolis A; Warehime J; Pauls RN.
Journal: 
Female Pelvic Medicine & Reconstructive Surgery. 24(2):130-134
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.

Randomized Trial of Concentrated Proanthocyanidins (PAC) for Acute Reduction of Bacteriuria in Male Veterans with Spinal Cord Injury "Utilizing Clean Intermittent Catheterization.

Posted: 
September 4, 2018
Authors: 
Sappal S; Goetz LL; Vince R; Klausner AP.
Journal: 
Spinal Cord Series and Cases. 4:58,
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.

Serious Adverse Events of Older Adults in Nursing Home and Community Intervention Trials.

Posted: 
September 4, 2018
Authors: 
Datta R; Trentalange M; Van Ness PH; McGloin JM; Guralnik JM; Miller ME; Walkup MP; Nadkarni N; Pahor M; Gill TM; Quagliarello V; Juthani-Mehta M; LIFE Study Group.
Journal: 
Contemporary Clinical Trials Communications. 9:77-80
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.

Standardised High Dose Versus Low Dose Cranberry Proanthocyanidin Extracts for the Prevention of Recurrent Urinary Tract Infection in Healthy Women [PACCANN]: a Double Blind Randomised Controlled Trial Protocol.

Posted: 
September 4, 2018
Authors: 
Asma B; Vicky L; Stephanie D; Yves D; Amy H; Sylvie D.
Journal: 
BMC Urology. 18(1):29
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.

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

Posted: 
September 4, 2018
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.

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