Limited effects of long-term daily cranberry consumption on the gut microbiome in a placebo-controlled study of women with recurrent urinary tract infections.

BACKGROUND: Urinary tract infections (UTIs) affect 15 million women each year in the United States, with > 20% experiencing frequent recurrent UTIs. A recent placebo-controlled clinical trial found a 39% reduction in UTI symptoms among recurrent UTI sufferers who consumed a daily cranberry beverage for 24 weeks. Using metagenomic sequencing of stool from a subset of these trial participants, we assessed the impact of cranberry consumption on the gut microbiota, a reservoir for UTI-causing pathogens such as Escherichia coli, which causes > 80% of UTIs. RESULTS: The overall taxonomic composition, community diversity, carriage of functional pathways and gene families, and relative abundances of the vast majority of observed bacterial taxa, including E. coli, were not changed significantly by cranberry consumption. However, one unnamed Flavonifractor species (OTU41), which represented ≤1% of the overall metagenome, was significantly less abundant in cranberry consumers compared to placebo at trial completion. Given Flavonifractor's association with negative human health effects, we sought to determine OTU41 characteristic genes that may explain its differential abundance and/or relationship to key host functions. Using comparative genomic and metagenomic techniques, we identified genes in OTU41 related to transport and metabolism of various compounds, including tryptophan and cobalamin, which have been shown to play roles in host-microbe interactions. CONCLUSION: While our results indicated that cranberry juice consumption had little impact on global measures of the microbiome, we found one unnamed Flavonifractor species differed significantly between study arms. This suggests further studies are needed to assess the role of cranberry consumption and Flavonifractor in health and wellbeing in the context of recurrent UTI. TRIAL REGISTRATION: Clinical trial registration number: ClinicalTrials.gov NCT01776021 .

Chronic consumption of a low calorie, high polyphenol cranberry beverage attenuates inflammation and improves glucoregulation and HDL cholesterol in healthy overweight humans: a randomized controlled trial.

PURPOSE: We studied the health benefits of low calorie cranberry beverage consumption on glucoregulation, oxidative damage, inflammation, and lipid metabolism in overweight but otherwise healthy humans. METHODS: 78 overweight or obese men and women (30-70 years; BMI 27-35 kg/m2) with abdominal adiposity (waist: hip > 0.8 for women and > 0.9 for men; waist: height ≥ 0.5) consumed 450 mL placebo or low calorie, high polyphenol cranberry extract beverage (CEB) daily for 8 week in a randomized, double-blind, placebo-controlled, parallel design trial. Blood and urine samples were collected after overnight fast at baseline and after 8 weeks of daily beverage consumption. Blood and urine samples were also collected during 3 oral glucose tolerance test (OGTT) challenges: (1) pre-intervention without the test beverages, (2) following a single dose of placebo or CEB at baseline (week 0), and (3) following a single dose of placebo or CEB at 8 week. RESULTS: Compared to placebo, a single CEB dose at baseline lowered endothelin-1 and elevated nitric oxide and the reduced:oxidized glutathione ratio (P < 0.05). Interferon-γ was elevated (P < 0.05) after a single CEB dose at baseline; however, after 8 week of CEB intervention, fasting C-reactive protein was lower (P < 0.05). CEB consumption for 8 week also reduced serum insulin and increased HDL cholesterol compared to placebo (P < 0.05). CONCLUSIONS: An acute dose of low calorie, high polyphenol cranberry beverage improved antioxidant status, while 8 week daily consumption reduced cardiovascular disease risk factors by improving glucoregulation, downregulating inflammatory biomarkers, and increasing HDL cholesterol.

Consumption of a cranberry juice beverage lowered the number of clinical urinary tract infection episodes in women with a recent history of urinary tract infection.

BACKGROUND: Urinary tract infections (UTIs) are among the most common bacterial infections and are often treated with antibiotics. Concerns about multidrug-resistant uropathogens have pointed to the need for safe and effective UTI-prevention strategies such as cranberry consumption. OBJECTIVE: We assessed the effects of the consumption of a cranberry beverage on episodes of clinical UTIs. DESIGN: In this randomized, double-blind, placebo-controlled, multicenter clinical trial, women with a history of a recent UTI were assigned to consume one 240-mL serving of cranberry beverage/d (n = 185) or a placebo (n = 188) beverage for 24 wk. The primary outcome was the clinical UTI incidence density, which was defined as the total number of clinical UTI events (including multiple events per subject when applicable) per unit of observation time. RESULTS: The dates of the random assignment of the first subject and the last subject's final visit were February 2013 and March 2015, respectively. The mean age was 40.9 y, and characteristics were similar in both groups. Compliance with study product consumption was 98%, and 86% of subjects completed the treatment period in both groups. There were 39 investigator-diagnosed episodes of clinical UTI in the cranberry group compared with 67 episodes in the placebo group (antibiotic use-adjusted incidence rate ratio: 0.61; 95% CI: 0.41, 0.91; P = 0.016). Clinical UTI with pyuria was also significantly reduced (incidence rate ratio: 0.63; 95% CI: 0.40, 0.97; P = 0.037). One clinical UTI event was prevented for every 3.2 woman-years (95% CI: 2.0, 13.1 woman-years) of the cranberry intervention. The time to UTI with culture positivity did not differ significantly between groups (HR: 0.97; 95% CI: 0.56, 1.67; P = 0.914). CONCLUSION: The consumption of a cranberry juice beverage lowered the number of clinical UTI episodes in women with a recent history of UTI. This study was registered at clinicaltrials.gov as NCT01776021.

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

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.

Consumption of cranberry beverage improved endogenous antioxidant status and protected against bacteria adhesion in healthy humans: a randomized controlled trial.

Consumption of polyphenol-rich foods is associated with lower risk from many chronic diseases. We hypothesized that a single dose of cranberry beverage would improve indices of oxidative stress, inflammation, and urinary antibacterial adhesion activity in healthy humans. Six males and 6 females (18-35 years; body mass index, 19-25 kg/m(2)) consumed placebo, cranberry leaf extract beverage, or low-calorie cranberry juice cocktail (LCJC) once in a randomized, double-blind, placebo-controlled cross-over experimental design trial. The washout period between beverages was 1 week. Blood was collected 0, 2, 4, 8, and 24 hours after beverage consumption for measuring oxidative and inflammatory biomarkers. Urine was collected at 0, 0 to 3, 3 to 6, 6 to 9, 9 to 12, and 24 hours postintervention to assess antibacterial adhesion activity. Consumption of cranberry leaf extract beverage elevated (P < .05) blood glutathione peroxidase activity, whereas LCJC consumption increased (P < .05) glutathione concentrations and superoxide dismutase activity compared with placebo. Cranberry leaf extract beverage and LCJC consumption had no effect on the inflammatory biomarkers measured as compared with placebo. At 0 to 3 hours postconsumption, urine from participants who consumed cranberry beverages had higher (P < .05) ex vivo antiadhesion activity against P-fimbriated Escherichia coli compared with placebo. An acute dose of cranberry beverages improved biomarkers of antioxidant status and inhibition of bacterial adhesion in urine.

Development of a fluorometric microplate antiadhesion assay using uropathogenic Escherichia coli and human uroepithelial cells.

A fluorometric microplate assay has been developed to determine Escherichia (E.) coli adhesion to uroepithelial cells (UEC). P-fimbriated E. coli were labeled with BacLight Green and preincubated 30 min with human urine or standard. Fluorescent-E. coli were added to UEC in mircoplates at a 400:1 ratio, incubated 1 h, and washed, and the fluorescence intensity was measured. Specific labeling and adherence were confirmed by flow cytometry. A myricetin (1) standard curve (0-30 µg/mL) was developed; the lower limit of detection was 0.1 µg/mL, and half-maximal inhibitory concentration was 0.88 µg/mL (intra- and interassay coefficients of variance were <10% and <15%, respectively). Vaccinium macrocarpon (cranberry) extracts, quercetin (2), and procyanidins B1 (3), B2 (4), and C1 (5) showed similar inhibition. Antiadhesion activity of urine samples from subjects (n = 12) consuming placebo or V. macrocarpon beverage determined using this assay was positively correlated (R(2) = 0.78; p < 0.01) with a radiolabeled-E. coli assay.

Pigmented potato consumption alters oxidative stress and inflammatory damage in men.

Pigmented potatoes contain high concentrations of antioxidants, including phenolic acids, anthocyanins, and carotenoids. These bioactive compounds have been implicated in the inhibition or prevention of cellular oxidative damage and chronic disease susceptibility. We assessed the effects of pigmented potato consumption on oxidative stress and inflammation biomarkers in adult males. Free-living healthy men (18-40 y; n = 12/group) consumed 150 g of cooked white- (WP), yellow- (YP), or purple-flesh potatoes (PP) once per day for 6 wk in a randomized study. Blood was collected at baseline and wk 6 to analyze total antioxidant capacity (TAC), DNA damage as assessed by plasma 8-hydroxydeoxyguanosine (8-OHdG), protein oxidation, lipid peroxidation, C-reactive protein (CRP), inflammatory cytokines, lymphoproliferation, NK cytotoxicity, and phenotypes. Potatoes were analyzed for TAC, phenolic acids, anthocyanins, and carotenoids. Compared with the WP group, the YP group had higher concentrations of phenolic acids (P < 0.002) and carotenoids (P < 0.001), whereas the PP group had higher concentrations of phenolic acids (P < 0.002) and anthocyanins (P < 0.001). Men who consumed YP and PP tended to have lower (P < 0.08) plasma IL-6 compared with those consuming WP. The PP group tended to have a lower plasma CRP concentration than the WP group (P = 0.07). The 8-OHdG concentration was lower in men who consumed either YP or PP compared with WP. Pigmented potato consumption reduced inflammation and DNA damage in healthy adult males. This offers consumers an improved nutritional choice in potato consumption.