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Urinary Tract

April 2010

Effect of cranberry drink on bacterial adhesion in vitro and vaginal microbiota in healthy females.

INTRODUCTION/OBJECTIVE: Cranberries have been shown to produce urinary metabolites that influence uropathogen adhesion and prevent urinary tract infections. This study was designed to determine if consuming reconstituted, unsweetened cranberry drink from extract retained its bioactive properties by reducing uropathogen adhesion without adversely affecting urinary calcium, magnesium and the vaginal microflora. MATERIALS AND METHODS: A randomized crossover study was undertaken in 12 healthy women consuming reconstituted unsweetened cranberry drink, CranActin or water. The urine was collected at 4 hours and 1 week of consumption and evaluated for antiadhesive properties and urinary pH, calcium and magnesium. Vaginal swabs were collected after 1 week of treatment to assess the vaginal microbiota by DGGE. RESULTS: The resultant urine produced by subjects who consumed 500 ml reconstituted cranberry extract twice per day, significantly reduced the adherence to epithelial cells of P-fi mbriated uropathogenic Escherichia coli and showed a tendency towards significance for two E. coli strains expressing fimbriae and an Enterococcus faecalis isolate. The cranberry drink treatment did not alter urinary pH, but reduced calcium and magnesium concentrations compared to water, although not to statistical significance. The reconstituted cranberry drink had no apparent detrimental effect on the vaginal microbiota. However, consuming twice daily resulted in an apparent loss of a potential pathogen from the vagina in 42% subjects. CONCLUSIONS: The present findings suggest that reconstituted cranberry drink may retain the ability to reduce the risk of UTI by inhibiting pathogen adhesion while not detrimentally affecting urinary pH or vaginal microbiota, or the risk of calculi.

Can J Urol. 2009 Dec;16(6):4901-7

Randomised trial of cranberry-lingonberry juice and Lactobacillus GG drink for the prevention of urinary tract infections in women.

OBJECTIVE: To determine whether recurrences of urinary tract infection can be prevented with cranberry-lingonberry juice or with Lactobacillus GG drink. Design: Open, randomised controlled 12 month follow up trial. SETTING: Health centres for university students and staff of university hospital. PARTICIPANTS: 150 women with urinary tract infection caused by Escherichia coli randomly allocated into three groups. Interventions: 50 ml of cranberry-lingonberry juice concentrate daily for six months or 100 ml of lactobacillus drink five days a week for one year, or no intervention. Main outcome measure: First recurrence of symptomatic urinary tract infection, defined as bacterial growth >/=10(5 )colony forming units/ml in a clean voided midstream urine specimen. RESULTS: The cumulative rate of first recurrence of urinary tract infection during the 12 month follow up differed significantly between the groups (P=0.048). At six months, eight (16%) women in the cranberry group, 19 (39%) in

the lactobacillus group, and 18 (36%) in the control group had had at least one recurrence. This is a 20% reduction in absolute risk in the cranberry group compared with the control group (95% confidence interval 3% to 36%, P=0.023, number needed to treat=5, 95% confidence interval 3 to 34). CONCLUSION: Regular drinking of cranberry juice but not lactobacillus seems to reduce the recurrence of urinary tract infection.

BMJ. 2001 Jun 30;322(7302):1571

Cranberry juice for the prevention of recurrent urinary tract infections: a randomized controlled trial in children.

OBJECTIVE: This study compares the effects of daily cranberry juice to those of Lactobacillus in children with recurrent urinary tract infections (UTIs). MATERIAL AND METHODS: Eighty-four girls aged between 3 and 14 years were randomized to cranberry, Lactobacillus or control in three treatment arms: G1, cranberry juice 50 ml daily (n=28); G2, 100 ml of Lactobacillus GG drink on 5 days a month (n=27); and G3, controls (n=29). The study lasted for 6 months. RESULTS: Only four subjects withdrew: 1/28 (3.5%) from G1, 1/27 (3.7%) from G2 and 2/29 (6.8%) from G3, because of poor compliance to the established protocol. There were 34 episodes of UTIs in this cohort: 5/27 (18.5%) in G1, 11/26 (42.3%) in G2 and 18/27 (48.1%) in the G3, with at least one episode of infection (p<0.05). CONCLUSION: These data suggest that daily consumption of concentrated cranberry juice can significantly prevent the recurrence of symptomatic UTIs in children.

Scand J Urol Nephrol. 2009;43(5):369-72

A randomized trial to evaluate effectiveness and cost effectiveness of naturopathic cranberry products as prophylaxis against urinary tract infection in women.

PURPOSE: To determine, from a societal perspective, the effectiveness and cost effectiveness of concentrated cranberry tablets, versus cranberry juice, versus placebo used as prophylaxis against lower urinary tract infection (UTI) in adult women. MATERIALS AND METHODS: One hundred fifty sexually active women aged 21 through 72 years were randomized for one year to one of three groups of prophylaxis: placebo juice + placebo tablets versus placebo juice + cranberry tablets, versus cranberry juice + placebo tablets. Tablets were taken twice daily, juice 250 ml three times daily. Outcome measures were: (1) a >50% decrease in symptomatic UTI’s per year (symptoms + >or= 100 000 single organisms/ml) and (2) a >50% decrease in annual antibiotic consumption. Cost effectiveness was calculated as dollar cost per urinary tract infection prevented. Stochastic tree decision analytic modeling was used to identify specific clinical scenarios for cost savings. RESULTS: Both cranberry juice and cranberry tablets statistically significantly decreased the number of patients experiencing at least 1 symptomatic UTI/year (to 20% and 18% respectively) compared with placebo (to 32%) (p<0.05). The mean annual cost of prophylaxis was $624 and $1400 for cranberry tablets and juice respectively. Cost savings were greatest when patients experienced >2 symptomatic UTI’s per year (assuming 3 days antibiotic coverage) and had >2 days of missed work or required protective undergarments for urgency incontinence. Total antibiotic consumption was less annually in both treatment groups compared with placebo. Cost effectiveness ratios demonstrated cranberry tablets were twice as cost effective as organic juice for prevention. CONCLUSIONS: Cranberry tablets provided the most cost-effective prevention for UTI.

Can J Urol. 2002 Jun;9(3):1558-62

Reduction of bacteriuria and pyuria after ingestion of cranberry juice.

OBJECTIVE—To determine the effect of regular intake of cranberry juice beverage on bacteriuria and pyuria in elderly women. DESIGN—Randomized, double-blind, placebo-controlled trial. SUBJECTS—Volunteer sample of 153 elderly women (mean age, 78.5 years). INTERVENTION—Subjects were randomly assigned to consume 300 mL per day of a commercially available standard cranberry beverage or a specially prepared synthetic placebo drink that was indistinguishable in taste, appearance, and vitamin C content but lacked cranberry content. OUTCOME MEASURES—A baseline urine sample and six clean-voided study urine samples were collected at approximately 1-month intervals and tested quantitatively for bacteriuria and the presence of white blood cells. RESULTS—Subjects randomized to the cranberry beverage had odds of bacteriuria (defined as organisms numbering > or = 10(5)/mL) with pyuria that were only 42% of the odds in the control group (P = .004). Their odds of remaining bacteriuric-pyuric, given that they were bacteriuric-pyuric in the previous month, were only 27% of the odds in the control group (P = .006). CONCLUSIONS—These findings suggest that use of a cranberry beverage reduces the frequency of bacteriuria with pyuria in older women. Prevalent beliefs about the effects of cranberry juice on the urinary tract may have microbiologic justification.

JAMA. 1994 Mar 9;271(10):751-4

Cranberry or trimethoprim for the prevention of recurrent urinary tract infections? A randomized controlled trial in older women.

OBJECTIVES: To compare the effectiveness of cranberry extract with low-dose trimethoprim in the prevention of recurrent urinary tract infections (UTIs) in older women. PATIENTS AND METHODS: One hundred and thirty-seven women with two or more antibiotic-treated UTIs in the previous 12 months were randomized to receive either 500 mg of cranberry extract or 100 mg of trimethoprim for 6 months. RESULTS: Thirty-nine of 137 participants (28%) had an antibiotic-treated UTI (25 in the cranberry group and 14 in the trimethoprim group); difference in proportions relative risk 1.616 (95% CI: 0.93, 2.79) P = 0.084. The time to first recurrence of UTI was not significantly different between the groups (P = 0.100). The median time to recurrence of UTI was 84.5 days for the cranberry group and 91 days for the trimethoprim group (U = 166, P = 0.479). There were 17/137 (12%) withdrawals from the study, 6/69 (9%) from the cranberry group and 11/68 (16%) from the trimethoprim group (P = 0.205), with a relative risk of withdrawal from the cranberry group of 0.54 (95% CI: 0.19, 1.37). CONCLUSIONS: Trimethoprim had a very limited advantage over cranberry extract in the prevention of recurrent UTIs in older women and had more adverse effects. Our findings will allow older women with recurrent UTIs to weigh up with their clinicians the inherent attractions of a cheap, natural product like cranberry extract whose use does not carry the risk of antimicrobial resistance or super-infection with Clostridium difficile or fungi.

J Antimicrob Chemother. 2009 Feb;63(2):389-95

Phytochemical, pharmacological and toxicological aspects of Hibiscus sabdariffa L.: a review.

This article reviews the reported phytochemical, pharmacological and toxicological properties of Hibiscus sabdariffa L. (English: roselle, red sorrel; Arabic: karkade), the calyces of which are used in many parts of the world to make cold and hot drinks. Nutritionally, these contain ascorbic acid (vitamin C). In folk medicine, the calyx extracts are used for the treatment of several complaints, including high blood pressure, liver diseases and fever. The pharmacological actions of the calyx extracts include strong in vitro and in vivo antioxidant activity. In rats and rabbits, the extract showed antihypercholesterolaemic, antinociceptive and antipyretic, but not antiinflammatory activities. In rat and man a strong antihypertensive action has been demonstrated. The effects of the calyx extracts on smooth muscles in vitro are variable, but they mostly inhibit the tone of the isolated muscles. In healthy men, consumption of H. sabdariffa has resulted in significant decreases in the urinary concentrations of creatinine, uric acid, citrate, tartrate, calcium, sodium, potassium and phosphate, but not oxalate. Oil extracted from the plant’s seeds has been shown to have an inhibitory effect on some bacteria and fungi in vitro. The plant extracts are characterized by a very low degree of toxicity. The LD50 of H. sabdariffa calyx extract in rats was found to be above 5,000 mg/kg. A single report has suggested that excessive doses for relatively long periods could have a deleterious effect on the testes of rats. In view of its reported nutritional and pharmacological properties and relative safety, H. sabdariffa and compounds isolated from it (for example, anthocyanins and Hibiscus protocatechuic acid) could be a source of therapeutically useful products. Copyright (c) 2005 John Wiley & Sons, Ltd.

Phytother Res. 2005 May;19(5):369-75

Screening of Thai medicinal plants for anticandidal activity.

Medicinal plants are often used in the treatment of various ailments. In this study, 23 of Thai medicinal plants were screened for their anticandidal activity against six pathogenic Candida species: C. albicans, C. glabrata, C. guilliermondii, C. krusei, C. parapsilosis and C. tropicalis. The methanol extract of Hibiscus sabdariffa L. fruit, Trigonostemon reidioides (Kurz) Craib root, Usnea siamensis Vain whole plant, Boesenbergia rotunda (L.) Mansf. rhizome, and Albizia myriophylla Benth. stem showed anticandidal activity against one or more species of Candida. Among them, A. myriophylla Benth. showed broad anticandidal activity. The susceptibility tests of A. myriophylla Benth. extract, in terms of minimal inhibitory concentrations (MIC) and minimal fungicidal concentration (MFC), were performed by the broth microdilution techniques as described by the Clinical Laboratory Standard Institute. MICs of A. myriophylla Benth. extract to all Candida species was ranged 100-500 mug ml(-1). The killing activity of A. myriophylla Benth. extract was fast acting against all Candida tested; the reduction in the number of CFU ml(-1) was >3 log(10) units (99.9%) in 2 h. This study indicates that A. myriophylla Benth. extract has considerable anticandidal activity, deserving further investigation for clinical applications for the treatment of candidiasis.

Mycoses. 2008 Jul;51(4):308-12

Pharmacokinetics of anthocyanidin-3-glycosides following consumption of Hibiscus sabdariffa L. extract.

Pharmacokinetic parameters of several dietary anthocyanins following consumption of Hibiscus sabdariffa L. extract were determined in 6 healthy volunteers. Subjects were given a single oral dose of 150 mL of Hibiscus sabdariffa L. extract yielding 62.6 mg of cyanidin-3-sambubioside, 81.6 mg of delphindin-3-sambubioside, and 147.4 mg of total anthocyanins (calculated as cyanidin equivalents). Within 7 hours, the urinary excretion of cyanidin-3-sambubioside, delphinidin-3-sambubioside, and total anthocyanins (ie, the sum of all quantifiable anthocyanidin glycosides) was 0.016%, 0.021%, and 0.018% of the administered doses, respectively. Maximum excretion rates were determined at 1.5 to 2.0 hours after intake. The dose-normalized plasma area under the curve estimates were 0.076, 0.032, and 0.050 ng x h/mL/mg for cyanidin-3-sambubioside, delphinidin-3-sambubioside, and total anthocyanins, respectively. The dose-normalized C(max) estimates were 0.036, 0.015, and 0.023 ng/mL/mg in the same sequence. They were reached each at 1.5 hours (median) after intake. The geometric means of t1/2 were 2.18, 3.34, and 2.63 hours for cyanidin-3-sambubioside, delphinidin-3-sambubioside, and total anthocyanins, respectively. The urinary excretion of intact anthocyanins was fast and appeared to be monoexponential. To evaluate the contribution of anthocyanins to the health-protecting effects of Hibiscus sabdariffa L. extract, it will be necessary to perform further studies on both the intact glycosides and their in vivo metabolites or conjugates in human plasma and urine.

J Clin Pharmacol. 2005 Feb;45(2):203-10