BACKGROUND: There is a lack of basic knowledge on the part of both clinicians and patients as to the indications for use and safety of herbs used during pregnancy and lactation. This is one article in a series that systematically reviews the evidence for herbs commonly used during pregnancy and lactation. OBJECTIVES: To systematically review the literature for evidence on the use, safety and pharmacology of cranberry, focusing on issues pertaining to pregnancy and lactation. METHODS: We searched 7 electronic databases and compiled data according to the grade of evidence found. RESULTS: There is no direct evidence of safety or harm to the mother or fetus as a result of consuming cranberry during pregnancy. Indirectly, there is good scientific evidence that cranberry may be of minimal risk, where a survey of 400 pregnant women did not uncover any adverse events when cranberry was regularly consumed. In lactation, the safety or harm of cranberry is unknown. CONCLUSIONS: Women experience urinary tract infections with greater frequency during pregnancy. Given the evidence to support the use of cranberry for urinary tract infections (UTIs) and its safety profile, cranberry supplementation as fruit or fruit juice may be a valuable therapeutic choice in the treatment of UTIs during pregnancy.

Abstract: Urinary ionized calcium was determined by a calcium activity electrode in 32 normal persons and in 54 patients with calcium-containing renal stones and without urinary tract infection. It was found to be 38 per cent higher in patients with calcium-containing renal stone in comparison to normal persons. However, this was not statistically significant. No consistant change in total or ionized calcium excretion was produced in normal volunteers by the administration of as much as 5 pints of cranberry juice. In patients with renal stones, the urinary ionized calcium was reduced during the cranberry juice ingestion by 50 per cent, which was statistically highly significant.

PURPOSE: This review provides practicing urologists with important basic information about urinary tract infections (UTIs) that can be applied to everyday clinical problems.

MATERIALS AND METHODS: A review is presented of provocative and controversial concepts in the current literature.

RESULTS: Bacterial virulence mechanisms are critical for overcoming the normal host defenses. Increasing antimicrobial resistance of uropathogens has led to reconsideration of traditional treatment recommendations in many areas. For effective patient management the first issue is to define complicating urological factors. Managing complicated urinary tract infections, particularly in urology, is determined by clinical experience to define the pertinent anatomy and to determine the optimal interventions. New clinical data are summarized on UTIs in long-term care patients, behavioral risks for UTI in healthy women and anatomical differences associated with an increased risk for UTI. The rationale is presented for UTI prophylaxis using cranberry juice, immunization and bacterial interference. Current treatment trends for UTI include empiric therapy (without urine culture and sensitivity testing), short-course therapy, patient-administered (self-start) therapy and outpatient therapy for uncomplicated pyelonephritis.

CONCLUSIONS: Recommendations for treating patients with UTIs have changed based on basic science and clinical experience.

In this review we assess the effectiveness of cranberry and blueberry products in preventing symptomatic urinary tract infections (UTIs). Selection criteria were randomised or quasi-randomised controlled trials of cranberry or blueberry juice/products for the prevention of symptomatic UTIs. A comprehensive search was undertaken in November 2006 whereupon two reviewers independently assessed and extracted data. Quality was assessed using Cochrane criteria. Relative risks (RR) were calculated where appropriate; otherwise a narrative synthesis was undertaken. No relevant trials of blueberry products were identified. Nine trials of cranberry products met the inclusion criteria. In four good quality randomised controlled trials (RCTs), cranberry products significantly reduced the incidence of symptomatic UTIs in 12 months (overall RR 0.65, 95% CI: 0.46-0.90) compared with placebo/control. Five trials were not included in the meta-analyses due to the lack of appropriate data. However, only one reported a significant result. Side effects were common, and losses to followup/withdrawals in several of the trials were high (> 40%). There is some evidence from four good quality RCTs that cranberry juice may decrease the number of symptomatic UTIs over a 12-month period, particularly in women with recurrent UTIs. It is uncertain whether it is effective in other susceptible groups.

Studies were undertaken to investigate the antiviral effects of comestible juices, especially cranberry juice, on non-related viral species. After exposure of bacteriophage T2 to a commercially available cranberry (Vaccinium macrocarpon) juice cocktail (CJ), virus infectivity titer was no longer detectible. After a 60-min exposure to orange (OJ) and grapefruit juices (GJ), phage infectivity was reduced to 25-35% of control, respectively. Similar data were observed for the bacteriophage T4. CJ inactivation of phage T4 was rapid, dose-dependent, and occurred at either 4 or 23 degrees C. Neither pH nor differences in sugar/carbohydrate levels among the juices may be ascribed to the recognized antiviral effects. Further studies were performed to identify the occurrence of antiviral activity by CJ to a mammalian enteric virus. The treatment of the simian rotavirus SA-11 with a 20% CJ suspension was sufficient to inhibit hemagglutination. Under scanning and transmission electron microscopy, CJ was observed to inhibit the adsorption of phage T4 to its bacterial host cells and prevented the replication of rotavirus in its monkey kidney (MA-104) host cells, respectively. The data suggest, for the first time, a non-specific antiviral effect towards unrelated viral species (viz., bacteriophages T2 and T4 and the simian rotavirus SA-11) by a commercially available cranberry fruit juice drink.

Cranberry (Vaccinium macrocarpon Ait.) ingestion has long been associated with prevention of urinary tract infections. The beneficial mechanism was historically thought to be due to the fruit acids causing a bacteriostatic effect in the urine. However, recently, a group of proanthocyanidins (PACs) with A-type linkages were isolated from cranberry which exhibit bacterial antiadhesion activity against both antibiotic susceptible and resistant strains of uropathogenic P-fimbriated Escherichia coli bacteria. The link between cranberry ingestion and maintenance of urinary tract health as well as the structural diversity, pharmacokinetics, quantification, and bacterial antiadhesion bioactivity of the A-linked cranberry PACs are reviewed.

The anti-adhesive effects of cranberry have been attributed to both interactions of its components with the surface of bacterial cells and to inhibition of p-fimbriae expression. Previous reports also suggested that the presence of cranberry juice changed the Gram stain characteristics of Escherichia coli. Here, we show that the morphology of E. coli is changed when grown in the presence of juice or extract from Vaccinium macrocarpon (cranberry). Gene expression analysis indicates the down regulation of flagellar basal body rod and motor proteins. Consistent with this finding and previous reports, the SEM images indicate a decrease in the visible p-fimbriae. The iodine used in Gram-staining protocols was found to interact differently with the bacterial membrane when cells were cultured in spiked media. Slight alterations in the Gram stain protocol demonstrated that culturing in the presence of cranberry juice does not change the Gram stain characteristics contradicting other reports.

This study evaluated the antibacterial efficacy of the consumption of cranberry capsules vs. placebo in the urine of healthy volunteers. A first double-blind, randomised, crossover trial involved eight volunteers who had followed three regimens, with or without cranberry, with a wash-out period of at least 6 days between each regimen. Twelve hours after consumption of cranberry or placebo hard capsules, the first urine of the morning was collected. Different Escherichia coli strains were cultured in the urine samples. Urinary antibacterial adhesion activity was measured in vitro using the human T24 epithelial cell-line, and in vivo using the Caenorhabditis elegans killing model. With the in-vitro model, 108 mg of cranberry induced a significant reduction in bacterial adherence to T24 cells as compared with placebo (p 0.001). A significant dose-dependent decrease in bacterial adherence in vitro was noted after the consumption of 108 and 36 mg of cranberry (p 0.001). The in-vivo model confirmed that E. coli strains had a reduced ability to kill C. elegans after growth in the urine of patients who consumed cranberry capsules. Overall, these in-vivo and in-vitro studies suggested that consumption of cranberry juice represents an interesting new strategy to prevent recurrent urinary tract infection.

OBJECTIVE: To determine whether Methenamine Hippurate (MH) or cranberry tablets prevent urinary tract infections (UTI) in people with neuropathic bladder following spinal cord injury (SCI).

STUDY DESIGN: Double-blind factorial-design randomized controlled trial (RCT) with 2 year recruitment period from November 2000 and 6 month follow-up.

SETTING: In total, 543 eligible predominantly community dwelling patients were invited to participate in the study, of whom 305 (56%) agreed.

METHODS: Eligible participants were people with SCI with neurogenic bladder and stable bladder management. All regimens were indistinguishable in appearance and taste. The dose of MH used was 1 g twice-daily. The dose of cranberry used was 800 mg twice-daily. The main outcome measure was the time to occurrence of a symptomatic UTI.

RESULTS: Multivariate analysis revealed that patients randomized to MH did not have a significantly longer UTI-free period compared to placebo (HR 0.96, 95% CI: 0.68-1.35, P=0.75). Patients randomized to cranberry likewise did not have significantly longer UTI-free period compared to placebo (HR 0.93, 95% CI: 0.67-1.31, P=0.70).

CONCLUSION: There is no benefit in the prevention of UTI from the addition of MH or cranberry tablets to the usual regimen of patients with neuropathic bladder following SCI.

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%) (p0.05). 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.