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 90 days prior to screening (OR: 2.28; 95% CI; 1.12, 4.67; p = 0.024), and living in France compared with the United States (OR: 0.17; 95% CI: 0.04, 0.79; p = 0.024). Three propensity categories were investigated (24-week probability 10%, 10%-21%, and > 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 10% probability, 0.73 (95% CI: 0.35, 1.53; p = 0.064) for those with 10% to 21% probability, and 0.58 (95% CI: 0.35, 0.97; p = 0.039) 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.

Background: Some studies have shown that cranberry (Vaccinium macrocarpon) has beneficial effects on the components of the metabolic syndrome (MetS), a condition characterized by a cluster of cardiovascular risk factors such as central obesity, hypertension, impaired glucose homeostasis, elevated triglycerides, and decreased HDL cholesterol levels. Cranberry is very rich in polyphenols, which may significantly reduce cardiovascular disease (CVD) risk. Main body of the abstract: Nutritional intervention studies have indicated that the intake of cranberries and cranberry products may have the following impact on metabolic health: (1) attenuate markers of obesity such as body weight, body mass index, and waist circumference; (2) reduce systolic and diastolic pressures; (3) decrease plasma concentrations of triglycerides and oxidized LDL-cholesterol, as well as increase HDL cholesterol; and (4) promote glucose homeostasis. In addition, nutritional intervention with cranberries could confer antioxidant and anti-inflammatory properties and the ability to reduce biomarkers of atherosclerosis associated with the MetS, such as homocysteine. Short conclusion: Although there has been promising results, particularly related to lipid profile and blood pressure, further research is needed to support the recommendation of cranberry intake as a nutritional intervention for the treatment of MetS.

Introduction: Although effectiveness of cranberry for preventing urinary tract infection (UTI) has been reported in Iranian traditional medicine and recent studies there is still controversy in this regard. Therefore, the present study was designed with a meta-analytic approach aiming to evaluate the effect of prophylaxis prescription of cranberry in prevention of UTI in children.Methods: In this study, a thorough search was performed in Medline, Embase, Web of Sciences, Scopus and CINHAL databases by the end of August 2017. Using keywords related to urinary tract infection combined with words related to cranberry, search strategy was designed. The articles were summarized and finally, the role of cranberry extract consumption in decreasing the incidence of UTI was evaluated by reporting odds ratio (OR) and 95 confidence interval (95 CI). Results: In the end, 10 studies were included (414 cases in control group and 380 in cranberry extract treatment group). Analyses showed that prescription of cranberry significantly reduced the odds of UTI manifestation in children compared to placebo (OR=0.31; 95 CI: 0.21 to 0.46; p

Urinary tract infections (UTI) are mostly caused by uropathogenic Escherichia coli (UPEC). Cranberry-based products have shown preventive effects against UTI, and this has been partially attributed to their A-type proanthocyanidin content. However, recent evidence reports phenyl- gamma -valerolactones as the most relevant urinary metabolites of cranberry procyanidins, and candidates these compounds as plausible responsible for the protective effects of cranberries against UTI. This paper studied the inhibition of the adherence of UPEC ATCCReg. 53503TM to T24 bladder epithelial cells by physiological concentrations of differently sulphated dihydroxyphenyl- gamma -valerolactones. Moreover, the transformations of these molecules in the cell media were evaluated by UHPLC-MSn. All dihydroxyphenyl- gamma -valerolactone derivatives showed anti-adhesive activity at 100 micro M, while 5-(3'-hydroxyphenyl)- gamma -valerolactone-4-O-sulphate also showed neuro-protective effects at 50 micro M. Some compounds underwent extensive metabolism during cell incubation, mainly deconjugation of sulphate moieties and opening of the lactone ring. These results shed light on the flavan-3-ol metabolites behind the prophylactic effect of cranberries against UTI.

Commensal bifidobacteria colonize the human gastrointestinal tract and catabolize glycans that are impervious to host digestion. Accordingly, Bifidobacterium longum typically secrete acetate and lactate as fermentative endproducts. This study tested the hypothesis that B. longum utilize cranberry-derived xyloglucans in a strain-dependent manner. Interestingly, the B. longum strain that efficiently utilizes cranberry xyloglucans secrete 2.0-2.5 moles acetate:lactate. The 1.5 ratio theoretical yield obtained in hexose fermentations shifts during xyloglucan metabolism. Accordingly, this metabolic shift is characterized by increased acetate and formate production at the expense of lactate. alpha-L-arabinofuranosidase, an arabinan endo-1,5-alpha-L-arabinosidase, and a beta-xylosidase with a carbohydrate substrate-binding protein and carbohydrate ABC transporter membrane proteins are upregulated (> 2-fold change), which suggests carbon flux through this catabolic pathway. Finally, syntrophic interactions occurred with strains that utilize carbohydrate products derived from initial degradation from a heterologous bacterium.IMPORTANCE This is a study of bacterial metabolism of complex cranberry carbohydrates termed xyloglucans that are likely not digested prior to reaching the colon. This is significant as bifidobacteria interact with this dietary compound to potentially impact human host health through energy and metabolite production by bacterial utilization of these substrates. Specific bacterial strains utilize cranberry xyloglucans as a nutritive source indicating unknown mechanisms that are not universal in bifidobacteria. In addition, xyloglucan metabolism proceeds using an alternative pathway could lead to further research to investigate mechanisms underlying this interaction. Finally, we observed cross-feeding between bacteria in which one strain degrades the cranberry xyloglucan to make it available to a second strain. Similar nutritive strategies are known to occur within the gut. In aggregate, this study may lead to novel foods or supplements to impact human health through rational manipulations of their microbiome.

The beneficial health effects of cranberries have been attributed to their (poly)phenol content. Recent studies have investigated the absorption, metabolism and excretion of cranberry (poly)phenols; however, little is known about whether they follow a dose response in vivo at different levels of intake. An acute double-blind randomized controlled trial in 10 healthy men with cranberry juices containing 409, 787, 1238, 1534 and 1910 mg total (poly)phenols was performed. Blood and urine were analyzed by UPLC-Q-TOF-MS. Sixty metabolites were identified in plasma and urine including cinnamic acids, dihydrocinnamic, flavonols, benzoic acids, phenylacetic acids, benzaldehydes, valerolactones, hippuric acids, catechols, and pyrogallols. Total plasma, but not excreted urinary (poly)phenol metabolites, exhibited a linear dose response (r2=0.74, p<0.05), driven by caffeic acid 4-O- beta -D-glucuronide, quercetin-3-O- beta -D-glucuronide, ferulic acid 4-O- beta -D-glucuronide, 2,5-dihydroxybenzoic acid, 2,4-dihydroxybenzoic acid, ferulic acid, caffeic acid 3-O- beta -D-glucuronide, sinapic acid, ferulic acid 4-O-sulfate, 3-hydroxybenzoic acid, syringic acid, vanillic acid-4-O-sulfate, (4R)-5-(3'-hydroxyphenyl)- gamma -valerolactone-4'-O-sulfate, 4-methylgallic acid-3-O-sulfate, and isoferulic acid 3-O-sulfate (all r2 >=0.89, p<0.05). Inter-individual variability of the plasma metabolite concentration was broad and dependent on the metabolite. Herein, we show that specific plasma (poly)phenol metabolites are linearly related to the amount of (poly)phenols consumed in cranberry juice. The large inter-individual variation in metabolite profile may be due to variations in the gut microbiome.

We investigated the anti-aging and redox state regulation effects by A-type proanthocyanidins (PACs)-rich cranberry concentrate (CBC) and its comparison with B-type PACs-rich grape seed extract (GSE). Using the Q-Extractive mass spectrometry, PACs dimer A and B were identified as predominant phenolic compounds of CBC and GSE, respectively, while epicatechin was present in both extracts. Using the d-galactose-induced aging mice model, effects were investigated via an 8-week oral gavage considering water-soluble vitamin E as the positive control. Both CBC and GSE reduced hepatic and brain thiobarbituric acid reactive substances, and plasma 8-isoprostane levels by 30-57%, 24-30% and 11-62%, respectively, and decreased brain and plasma monoamine oxidase activities by 27-59% and 65-71%, respectively. CBC could improve hepatic glutathione peroxidase activity by 42%, while GSE increased hepatic superoxide dismutase activity by 13%. Therefore, both extracts exerted anti-aging effects probably via regulating in vivo redox state. However, neither generated any effect on catalase activities.

Cranberry (Vaccinium macrocarpon Aiton) is used to treat noncomplicated urinary tract infections (UTIs). A-type procyanidins (PAC-A) are considered the active constituents able to inhibit bacterial adhesion to the urinary epithelium. However, the role of PAC-A in UTIs is debated, because of their poor bioavailability, extensive metabolism, limited knowledge about urinary excretion, and contradictory clinical trials. The effects of 35-day cranberry supplementation (11 mg/kg PAC-A, 4 mg/kg PAC-B) were studied in healthy rats using a ultra performance liquid chromatography-mass spectrometry (UPLC-MS)-based metabolomics approach. Microbial PAC metabolites, such as valeric acid and valerolactone derivatives, were related to cranberry consumption. An increased urinary excretion of glucuronidated metabolites was also observed. In a further experiment, urine samples were collected at 2, 4, 8, and 24 h after cranberry intake and their antiadhesive properties were tested against uropathogenic Escherichia coli. The 8 h samples showed the highest activity. Changes in urinary composition were studied by ultra performance liquid chromatography-time-of-flight (UPLC-QTOF), observing the presence of PAC metabolites. The PAC-A2 levels were measured in all collected samples, and the highest amounts, on the order of ng/mL, were found in the samples collected after 4 h. Results indicate that the antiadhesive activity against uropathogenic bacteria observed after cranberry consumption is ascribable to PAC-A metabolites rather than to a direct PAC-A effect, as the measured PAC-A levels in urine was lower than those reported as active in the literature.

PURPOSE: We sought to clarify the association between cranberry intake and the prevention of urinary tract infections. MATERIALS AND METHODS: This systematic review, which complies with the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) statement, was done as a meta-analysis and trial sequential analysis of clinical trials. RESULTS: The findings clearly showed the potential use of cranberries for the clinical condition of urinary tract infection. Cranberry products significantly reduced the incidence of urinary tract infections as indicated by the weighted risk ratio (0.6750, 95% CI 0.5516-0.7965, p <0.0001). The results of subgroup analysis demonstrated that patients at some risk for urinary tract infections were more susceptible to the effects of cranberry ingestion. CONCLUSIONS: The results of the current study could be used by physicians to recommend cranberry ingestion to decrease the incidence of urinary tract infections, particularly in individuals with recurrent urinary tract infections. This would also reduce the administration of antibiotics, which could be beneficial since antibiotics can lead to the worldwide emergence of antibiotic resistant microorganisms.

An extract prepared from cranberry juice by dialysis known as nondialyzable material (NDM) has been shown previously to possess anti-adhesion activity toward microbial species including oral bacteria, uropathogenic Escherichia coli and Helicobacter pylori. Bioassay-guided fractionation of cranberry NDM was therefore undertaken to identify the anti-adhesive constituents. An aqueous acetone-soluble fraction (NDMac) obtained from Sephadex LH-20 inhibited adhesion-linked activities by oral bacteria, including co-aggregation of oral bacteria Fusobacterium nucleatum with Streptococcus sanguinis or Porphyromonas gingivalis, and biofilm formation by Streptococcus mutans. Analysis of NDMac and subsequent subfractions by MALDI-TOF MS and 1H NMR revealed the presence of A-type proanthocyanidin oligomers (PACs) of 3-6 degrees of polymerization composed of (epi)catechin units, with some (epi)gallocatechin and anthocyanin units also present, as well as quercetin derivatives. Subfractions containing putative xyloglucans in addition to the mixed polyphenols also inhibit biofilm formation by S. mutans (MIC = 125-250 mug mL-1). These studies suggest that the anti-adhesion activities of cranberry NDM on oral bacteria may arise from a combination of mixed polyphenol and non-polyphenol constituents.