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Urinary Tract Health and Antibacterial Benefits: Human

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Pilot Study to Evaluate Compliance and Tolerability of Cranberry Capsules in Pregnancy for the Prevention of Asymptomatic Bacteriuria

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Authors
Wing DA, Rumney PJ, Hindra S, Guzman L, Le J, Nageotte M
Journal
J Altern Complement Med 21(11):700-6
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.

A 1H NMR-based approach to investigate metabolomic differences in the plasma and urine of young women after cranberry juice or apple juice consumption.

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Authors
Liu HY, Tayyari F, Khoo C, Gu LW
Journal
J Funct Food 14:76-86
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.

A randomized, double-blind, placebo-controlled trial to assess the bacterial anti-adhesion effects of cranberry extract beverages

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Authors
Kaspar KL, Howell AB, Khoo C
Journal
Food Funct 6(4):1212-7
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.

American cranberry (proanthocyanidin 120 mg): its value for the prevention of urinary tracts infections after ureteral catheter placement.

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Authors
Barnoiu OS, Sequeira-Garcia Del Moral J, Sanchez-Martinez N, Diaz-Molina P, Flores-Sirvent L, Baena-Gonzalez V
Journal
Actas Urol Esp 39(2):112-7
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.

Antibiotic susceptibility of urinary isolates in nursing home residents consuming cranberry capsules versus placebo

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Authors
Madden GR, Argraves SM, Van Ness PH, Juthani-Mehta M
Journal
Infect Control Hosp Epidemiol 36(3):356-7
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.

Cranberry fruit powder (Flowens™)improves lower urinary tract symptoms in men: a double-blind, randomized, placebo-controlled trial

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Authors
Vidlar A, Student Jr V, Vostalova J, Fromentin E, Roller M, Simanek V, Student V
Journal
World J Urol DOI 10.1007/s00345-015-1611-7
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.

Cranberry juice capsules and urinary tract infection after surgery: results of a randomized trial

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Authors
Foxman B, Cronenwett AE, Spino C, Berger MB, Morgan DM
Journal
Am J Obstet Gynecol 213(2):194.e1-8
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.

Cranberry supplementation in the prevention of non-severe lower urinary tract infections: a pilot study.

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Authors
Ledda A, Bottari A, Luzzi R, Belcaro G, Hu S, Dugall M, Hosoi M, Ippolito E, Corsi M, Gizzi G, Morazzoni P, Riva A, Giacomelli L, Togni S
Journal
Eur Rev Med Pharmacol Sci 19(1):77-80,
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.

Standardized cranberry capsules for radiation cystitis in prostate cancer patients in New Zealand: a randomized double blinded, placebo controlled pilot study

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Authors
Hamilton K, Bennett NC, Purdie G, Herst PM
Journal
Support Care Cancer 23(1):95-102
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.

Cranberry versus placebo in the prevention of urinary infections in multiple sclerosis: a multicenter, randomized, placebo-controlled, double-blind trial.

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Authors
Gallien P, Amarenco G, Benoit N, Bonniaud V, Donzé C, Kerdraon J, de Seze M, Denys P, Renault A, Naudet F, Reymann JM.
Journal
Mult Scler 20(9):1252-1259.
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.