Purpose: Extensive inter-individual variability exists in the production of flavan-3-ol metabolites. Preliminary metabolic phenotypes (metabotypes) have been defined, but there is no consensus on the existence of metabotypes associated with the catabolism of catechins and proanthocyanidins. This study aims at elucidating the presence of different metabotypes in the urinary excretion of main flavan-3-ol colonic metabolites after consumption of cranberry products and at assessing the impact of the statistical technique used for metabotyping. Methods: Data on urinary concentrations of phenyl-P-valerolactones and 3-(hydroxyphenyl)propanoic acid derivatives from two human interventions has been used. Different multivariate statistics, principal component analysis (PCA), cluster analysis, and partial least square-discriminant analysis (PLS-DA), have been considered. Results: Data pre-treatment plays a major role on resulting PCA models. Cluster analysis based on k-means and a final consensus algorithm lead to quantitative-based models, while the expectation-maximization algorithm and clustering according to principal component scores yield metabotypes characterized by quali-quantitative differences in the excretion of colonic metabolites. PLS-DA, together with univariate analyses, has served to validate the urinary metabotypes in the production of flavan-3-ol metabolites and to confirm the robustness of the methodological approach.Conclusions: This work proposes a methodological workflow for metabotype definition and highlights the importance of data pre-treatment and clustering methods on the final outcomes for a given dataset. It represents an additional step toward the understanding of the inter-individual variability in flavan-3-ol metabolism.

This open pilot registry study aimed to evaluate and compare the prophylactic effects of PycnogenolR or cranberry extract in subjects with previous, recurrent urinary tract infections (UTI) or interstitial cystitis (IC). Methods: Inclusion criteria were recurrent UTI or IC. One subject group was supplemented with 150 mg/day PycnogenolR, another with 400 mg/day cranberry extract, and a group served as a control in a 2-month open follow-up. Results: 64 subjects with recurrent UTI/IC completed the study. The 3 groups of subjects were comparable at baseline. All subjects had significant symptoms (minor pain, stranguria, repeated need for urination, and lower, anterior abdominal pain) at inclusion. In the course of the study, the subjects reported no tolerability problems or side effects. The incidence of UTI symptoms, in comparison with the period before inclusion in the standard management (SM) group, decreased significantly; there was a more pronounced decrease in the rate of recurrent infections in the PycnogenolR group (p < 0.05). The improvement in patients supplemented with PycnogenolR was significantly superior to the effects of cranberry. At the end of the study, all subjects in the PycnogenolR group were infection-free (p < 0.05vs. cranberry). Significantly, more subjects were completely symptom-free after 2 months of management with PycnogenolR (20/22) than with SM (18/22) and cranberry (16/20). Conclusions: This pilot registry suggests that 60 days of PycnogenolR supplementation possibly decrease the occurrence of UTIs and IC without side effects and with an efficacy superior to cranberry.

Helicobacter pylori infection is one of the most common chronic bacterial infections. Cranberry has been suggested for H. pylori eradication. We aimed to conduct the first meta-analysis to summarise current evidence on effects of cranberry supplementation on H. pylori eradication in H. pylori positive subjects. We searched the online databases up to December 2020. Four randomised clinical trials (RCT) were included with human subjects, investigating the effect of cranberry on H. pylori eradication. The pooled results were expressed as the OR with 95 % CI. Based on five effect sizes with a total sample size of 1935 individuals, we found that according to the OR, there was a positive effect of cranberry supplementation on H. pylori eradication, increasing the chance of H. pylori eradication by 1.27 times, but this relationship was not statistically significant (overall OR: 1.27; 95 % CI 0.63, 2.58). The results also indicated the moderate between-study heterogeneity (I2 = 63.40 %; P = 0.03) of the studies. However, there were no significant differences in some subgroup analyses in the duration of treatment, the duration of follow-up and the Jadad score. Our findings revealed that although cranberry had a positive effect on H. pylori eradication in adults, this effect was not statistically significant. Due to the small number of included studies and moderate heterogeneities, the potential of cranberry supplementation on H. pylori eradication should be validated in large, multicentre and well-designed RCT in the future.

A number of clinical trials support the use of standardized cranberry supplement products for prevention of urinary tract infections; however, products that are not well-characterized for sufficient levels of bioactive components may contribute to negative clinical outcomes. Cranberry supplements for consumer use are not regulated and can be formulated different ways using cranberry juice, pomace or various combinations. This can lead to consumer confusion regarding effectiveness of individual products. The current study compared two commercial supplement products, one made from cranberry juice extract and the other from a blend of whole cranberry. The influence of formulation and proanthocyanidin (PAC) solubility on in vitro and ex vivo P-fimbriated Escherichia coli bacterial anti-adhesion activity (AAA) was determined. Both supplement products as well as whole, frozen cranberries were chromatographically separated into crude polyphenolic, sugar and acid fractions. In vitro AAA testing of all fractions confirmed that only those containing soluble PACs elicited activity. The cranberry juice extract product had higher soluble PAC content than the whole cranberry blended product, which contained mainly insoluble PACs. The influence of soluble and insoluble PAC levels in each product on the urinary (ex vivo) AAA was determined following ingestion. The juice extract product was associated with significantly higher urinary AAA than that of the whole berry blended product when consumed once daily over the 1-week intervention period.

Aim: Cranberries (Vaccinium macrocarpon) are traditionally used in prevention of urinary tract infections (UTIs). The authors' aim was to evaluate effects of a supplement containing cranberry extract, pumpkin seed extract, vitamin C, and vitamin B-2 on recurrent uncomplicated UTIs in women and their intestinal microbiota.Methods: A prospective, uncontrolled exploratory study was conducted in women with recurrent uncomplicated UTIs. The primary exploratory outcome was the number of UTIs in a 6-month prospective observation period compared with a 6-month retrospective period. Further outcomes included number of antibiotics, quality of life (SF-36), intestinal microbiota (assessed by 16S rRNA amplicon sequencing), and evaluation questions. Parameters were assessed at baseline and after 1, 2, and 7 months (start of intake of cranberry supplement after 1 month for 6 months). p-Values were calculated with the pairwise Wilcoxon signed-rank test for alpha diversity and permutational multivariate analysis of variance.Results: Twenty-three women (aged 52.7 +/- 12.4 years) were included in the study. Participants reported 2.2 +/- 0.8 UTIs (at baseline) in the previous 6 months. After 6 months of cranberry intake, participants reported a significant decrease to 0.5 +/- 0.9 UTIs (p < 0.001). Number of antibiotic therapies was also significantly (p < 0.001) reduced by 68% during 6 months of cranberry intake (0.14 +/- 0.35) when compared with 6 months retrospectively (1.14 +/- 0.71). The SF-36 physical component score increased from 44.9 +/- 5.5 at baseline to 45.7 +/- 4.6 at 7 months (p = 0.16). The SF-36 mental component score decreased slightly from the baseline value of 46.5 +/- 6.5 to 46.2 +/- 6.4 at 7 months (p = 0.74). No significant intragroup mean changes at genus, family, or species level for alpha and beta diversity within the intestinal microbiota were found. In the evaluation questions, participants rated the cranberry extract positively and considered it beneficial. The supplement intake was safe.Conclusions: This study shows that women with recurrent uncomplicated UTIs benefit from cranberry intake. Future larger clinical studies with further investigation of the mechanisms of action are required to determine the effects of cranberries on participants with uncomplicated UTIs.

Importance There is little consensus on an effective nonantibiotic agent for the prevention of urinary tract infection (UTI) after pelvic reconstructive surgery. Objective The aim of the study was to investigate the impact of methenamine hippurate with cranberry capsules on rates of UTI after pelvic reconstructive surgery, among patients requiring short-term catheterization. Study Design In this randomized, double-blinded placebo-controlled trial, patients discharged with a catheter after pelvic reconstructive surgery were approached to participate. Participants were randomized to receive cranberry with methenamine or cranberry with placebo. Primary outcome was number of UTIs treated within 1 week after surgery. Secondary outcomes included incidence of UTIs treated within 6 weeks postoperatively, bacterial species on culture, urinary pH, catheter duration, patient adherence, and satisfaction. A sample size of 88 participants per arm was planned. Results From June 2019 to July 2021, 185 patients were randomized and 182 analyzed; 89 received placebo and 93 received methenamine. Both groups were similar. Incidence of UTI at 1 week was significantly higher in the placebo group (79.8%) compared with the methenamine group (66.7%; odds ratio, 1.97; 95% confidence interval, 1.01-3.87; P = 0.048). This difference increased by 6 weeks postoperatively (89.9% vs 72.0%; odds ratio, 3.45; 95% confidence interval, 1.51-7.87; P = 0.003). There were fewer pseudomonal UTIs in the methenamine group (P = 0.041). Duration of catheterization and urinary pH were similar. Overall adherence and level of satisfaction was high. Conclusions In this high-risk population, methenamine was well tolerated and significantly reduced UTI rates. Methenamine with cranberry should be considered as an effective prophylactic therapy to reduce this common complication after pelvic surgery.

AIMS: Urinary tract infection (UTI) is a common complication after pelvic floor surgery. Antibiotics as prophylaxis may reduce the prevalence of UTI's by 50%, but bacterial resistance may be a large disadvantage, necessitating the search for other possible prophylactic options. Recent research found a 50% reduction in the rate of UTI's with the use of cranberry capsules after elective gynecologic surgery, suggesting that cranberry capsules may serve as a good prophylaxis. The aim of this study was to assess whether perioperative cranberry prophylaxis reduces the risk of clinical overt UTI after elective pelvic floor surgery with indwelling catheter. METHODS: We conducted a single-center randomized, double-blind, placebo-controlled trial. Women were given cranberry capsules twice daily or identical placebo for 6 weeks, starting the day before surgery. The main endpoint of the trial was the incidence of UTI within 6 weeks after surgery, defined as clinical diagnosis and treatment of UTI by the medical doctor. Analyses were performed with the intention to treat. RESULTS: Two hundred ten participants were included, 105 in each arm. There was no significant difference in the prevalence of UTI between the cranberry arm (n = 13, 12.4%) and the placebo arm (n = 21, 20.0%; P = .13), but the prevalence in both arms was lower than anticipated. CONCLUSIONS: This trial shows no beneficial effect of adequately dosed cranberry prophylaxis in women undergoing pelvic floor surgery, although such effect cannot be ruled out in settings with a higher prevalence of UTI's.

BACKGROUND: Most women experience a urinary tract infection (UTI) at least once in their lifetime. The present study determined the efficacy and safety of a combination of Lactobacillus paracasei LC11, cranberry and D-mannose (Lactoflorene Cist R) in the prophylaxis of recurrent uncomplicated UTIs in premenopausal women. METHODS: This single-centre study enrolled premenopausal women aged 18-50 years with an acute UTI and a history of recurrent uncomplicated UTIs. Patients were first treated with fosfomycin (3 g once a day for 2 days) to eliminate any underlying infection, followed by treatment with Lactoflorene Cist R once a day for 10 days/month for 90 days (Group 1), Lactoflorene Cist R once daily for 90 days (Group 2) or no treatment (Group 3; control). The main study endpoint was the rate of UTI recurrence during the study period. Any adverse events with treatment were also recorded. RESULTS: A total of 55 women (mean age 39.3 years; range: 20-46) were enrolled in the study. A significantly higher proportion of patients in the control group experienced UTIs during the study period compared with the two treatment groups (52.9% vs 16.0% in Group 1 and 15.5% in group 2; p < 0.01). Similarly, a higher proportion of patients in Group 1 (65.8%) and Group 2 (68.7%) remained UTI-free during the study versus the control group. No adverse events were reported in the treated patients. CONCLUSION: Prophylactic treatment with Lactoflorene Cist R was effective and safe in the management of recurrent uncomplicated UTIs in premenopausal women.

The objectives of this research were to investigate urinary metabolome modifications and discover potential intake biomarkers in young women after cranberry juice consumption. Fifteen female college students were given either cranberry juice or apple juice for three days using a cross-over design. Urine samples were collected before and after juice consumption. The metabolome in the urine was analyzed using UHPLC-Q-orbitrap-HRMS-based metabolomics followed by orthogonal partial least squares-discriminant analyses (OPLS-DA). An S-plot was used to identify discriminant metabolites. Validated OPLS-DA analyses showed that cranberry juice consumption significantly altered the urinary metabolome. Compared to the baseline urine or urine after apple juice consumption, cranberry juice consumption increased urinary excretion of both exogenous and endogenous metabolites. The tentatively identified exogenous metabolites included quinic acid, coumaric acid, 4-hydroxy-5-(hydroxyphenyl)-valeric acid-O-sulphate, 5-(dihydroxyphenyl)-P-valerolactone sulfate, diphenol glucuronide, 3,4-dihydroxyphenyl propionic acid, 3-(hydroxyphenyl) propionic acid, 4-O-methylgallic acid, trihydroxybenzoic acid and 1,3,5-trimethoxybenzene. Modifications of endogenous metabolites after cranberry juice consumption included the increases in homocitric acid, hippuric acid, 3-hydroxy-3-carboxymethyl-adipic acid, (2)3-isopropylmalate, pimelic acid and N-acetyl-L-glutamate 5-semialdehyde. These metabolites may serve as urinary biomarkers of cranberry juice consumption and contribute to the bioactivities of cranberries against urinary tract infection.

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.