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Research Abstracts By Year

A review and critical analysis of the scientific literature related to 100% fruit juice and human health

Posted: September 30, 2015
Authors: Hyson DA
Journal: Adv Nutr 6(1):37-51

Abstract: The association between the consumption of pure (100%) fruit juice (PFJ) and human health is uncertain. The current review summarizes data published between 1995 and 2012 related to PFJ with a focus on juices that are widely available and studied in forms representing native juice without supplemental nutrients or enhanced phytochemical content. The effects of apple, cranberry, grape, grapefruit, orange, and pomegranate PFJ intake on outcomes linked to cancer, cardiovascular disease, cognition, hypertension, inflammation, oxidation, platelet function, urinary tract infection, and vascular reactivity are reviewed. Implications for bodyweight regulation are also addressed. The collective data are provocative although challenges and unanswered questions remain. There are many plausible mechanisms by which PFJ might be protective, and investigation of its effects on human health and disease prevention must remain an active area of research

A 1H NMR-based approach to investigate metabolomic differences in the plasma and urine of young women after cranberry juice or apple juice consumption.

Posted: September 28, 2015
Authors: Liu HY, Tayyari F, Khoo C, Gu LW
Journal: J Funct Food 14:76-86

Abstract: The overall metabolic changes caused by cranberry juice or apple juice consumption using a global 1H NMR-based metabolomics approach were investigated. Eighteen female college students were given either cranberry or apple juice for three days using a cross-over design. Plasma and urine samples were collected and analyzed using 1H NMR-based metabolomics followed by multivariate analyses. No metabolic difference was observed in plasma before and after juice consumption. However, metabolome in plasma and urine after cranberry juice consumption were different from those after apple juice consumption. Cranberry juice consumption caused a greater increase in urinary excretion of hippuric acid and a higher level of citric acid in the plasma. Furthermore, cranberry juice decreased the plasma level of lactate, D-glucose, and two unidentified metabolites compared to apple juice consumption. The metabolomic changes caused by cranberry juice consumption may help to explain its reported health benefits.

A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice

Posted: September 28, 2015
Authors: Anhe FF, Roy D, Pilon G, Dudonne S, Matamoros S, Varin TV, Garofalo C, Moine Q, Desjardins Y, Levy E, Marette A
Journal: Gut 64(6):872-883.

Abstract: Objective: The increasing prevalence of obesity and type 2 diabetes (T2D) demonstrates the failure of conventional treatments to curb these diseases. The gut microbiota has been put forward as a key player in the pathophysiology of diet-induced T2D. Importantly, cranberry (Vaccinium macrocarpon Aiton) is associated with a number of beneficial health effects. We aimed to investigate the metabolic impact of a cranberry extract (CE) on high fat/high sucrose (HFHS)-fed mice and to determine whether its consequent antidiabetic effects are related to modulations in the gut microbiota. Design C57BL/6J mice were fed either a chow or a HFHS diet. HFHS-fed mice were gavaged daily either with vehicle (water) or CE (200 mg/kg) for 8 weeks. The composition of the gut microbiota was assessed by analysing 16S rRNA gene sequences with 454 pyrosequencing. Results: CE treatment was found to reduce HFHS-induced weight gain and visceral obesity. CE treatment also decreased liver weight and triglyceride accumulation in association with blunted hepatic oxidative stress and inflammation. CE administration improved insulin sensitivity, as revealed by improved insulin tolerance, lower homeostasis model assessment of insulin resistance and decreased glucose-induced hyperinsulinaemia during an oral glucose tolerance test. CE treatment was found to lower intestinal triglyceride content and to alleviate intestinal inflammation and oxidative stress. Interestingly, CE treatment markedly increased the proportion of the mucin-degrading bacterium Akkermansia in our metagenomic samples. Conclusions: CE exerts beneficial metabolic effects through improving HFHS diet-induced features of the metabolic syndrome, which is associated with a proportional increase in Akkermansia spp. population.

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

Posted: September 28, 2015
Authors: Kaspar KL, Howell AB, Khoo C
Journal: Food Funct 6(4):1212-7

Abstract: 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.

Adult consumers of cranberry juice cocktail have lower C-reactive protein levels compared with nonconsumers.

Posted: September 28, 2015
Authors: Duffey KJ, Sutherland LA
Journal: Nutr Res 35(2):118-26

Abstract: Flavonoids are important bioactive plant constituents found in abundance in berries, including cranberries. Cranberry beverages have been shown to beneficially impact urinary and cardiovascular health in clinical and observational studies, but their association with anthropometric outcomes is unknown. We examined the association between cranberry juice cocktail (CJC) consumption with flavonoid intake, and cardiometabolic and anthropometric outcomes among adults in the US data for adults (>19 years, n = 10334) were drawn from cross-sectional National Health and Nutrition Examination Survey combined 2005-2008 survey. We hypothesized that CJC consumers will have lower anthropometric measures and healthier cardiometabolic profiles, including lower cholesterol and C-reactive protein (CRP). A CJC consumer (n = 330) was defined as anyone consuming CJC for 2 nonconsecutive 24-hour dietary recalls. We used multivariate linear regression models to examine differences in anthropometric and cardiometabolic outcomes comparing CJC consumers to nonconsumers controlling for important confounders. Consumers drank an average 404 mL (14 fl oz) of CJC for 2 days and did not have higher total energy intakes compared with nonconsumers (mean [SD], 2259 [79] vs 2112 [24], respectively). In fully adjusted models, adult CJC consumers had significantly lower levels of CRP (mean [SD], -0.13 [0.05]; P = .015), results that were strengthened after further adjustment for body mass index (mean [SD], -0.98 [0.04]; P = .027). Trends toward lower weights and lower levels of cholesterol did not reach statistical significance. Intake of cranberry polyphenols may play a role in promoting anti-inflammatory markers among CJC consumers, specifically lowering CRP levels

American cranberry (proanthocyanidin 120 mg): its value for the prevention of urinary tracts infections after ureteral catheter placement.

Posted: September 28, 2015
Authors: Barnoiu OS, Sequeira-Garcia Del Moral J, Sanchez-Martinez N, Diaz-Molina P, Flores-Sirvent L, Baena-Gonzalez V
Journal: Actas Urol Esp 39(2):112-7

Abstract: INTRODUCTION: Urinary tract infection (UTI) is among the most frequent complications after urinary tract surgical procedures, mainly when catheter placement is necessary. Although the use of American cranberry has been related with a reduced risk of UTI, there is no study reporting the value of its prevention effect against catheter-associated urinary tract infections.
MATERIAL AND METHODS: A prospective trial comparing UTI rate (positive urine culture) among 31 patients with double J catheter (JJ) and adding American cranberry (120 mg) in routine prophylactic therapy, and 31 patients with JJ catheter only receiving routine prophylactic therapy.
RESULTS: Regarding general characteristics of the populations no significant difference among groups have been found. Only significant differences have been observed when the variables ""cranberry treatment"" and ""dwell time of JJ catheter"" were related. ""Dwell time of JJ catheter"" was higher in patients with UTI (35.9 compared 28.5 days [P=.03]). UTI percentage was lower in cranberry supplemented patient group (12.9 compared to 38.7% [P=.04]).
CONCLUSIONS: We can conclude that American cranberry (120 mg) has an adjuvant effect in the prevention of UTI in patients with JJ catheter after surgery.

Anti-Adhesive Activity of Cranberry Phenolic Compounds and Their Microbial-Derived Metabolites against Uropathogenic Escherichia coli in Bladder Epithelial Cell Cultures

Posted: September 28, 2015
Authors: de Llano DG, Esteban-Fernandez A, Sanchez-Patan F, Martinlvarez PJ, Moreno-Arribas MV, Bartolome B
Journal: Int J Mol Sci 16(6):12119-30

Abstract: Cranberry consumption has shown prophylactic effects against urinary tract infections (UTI), although the mechanisms involved are not completely understood. In this paper, cranberry phenolic compounds and their potential microbial-derived metabolites (such as simple phenols and benzoic, phenylacetic and phenylpropionic acids) were tested for their capacity to inhibit the adherence of uropathogenic Escherichia coli (UPEC) ATCC53503TM to T24 epithelial bladder cells. Catechol, benzoic acid, vanillic acid, phenylacetic acid and 3,4-dihydroxyphenylacetic acid showed anti-adhesive activity against UPEC in a concentration-dependent manner from 100-500 micro M, whereas procyanidin A2, widely reported as an inhibitor of UPEC adherence on uroepithelium, was only statistically significant (p < 0.05) at 500 micro M (51.3% inhibition). The results proved for the first time the anti-adhesive activity of some cranberry-derived phenolic metabolites against UPEC in vitro, suggesting that their presence in the urine could reduce bacterial colonization and progression of UTI.

Antibiotic susceptibility of urinary isolates in nursing home residents consuming cranberry capsules versus placebo

Posted: September 28, 2015
Authors: Madden GR, Argraves SM, Van Ness PH, Juthani-Mehta M
Journal: Infect Control Hosp Epidemiol 36(3):356-7

Abstract: Urinary tract infection (UTI) is the most common infection
among nursing home residents, and the microorganisms pre-valent in this setting pose significant challenges for treatment. Cranberries (Vaccinium macrocarpon Aiton
) are thought to reduce UTIs; this view is supported by a placebo-controlled trial showing lower rates of bacteriuria plus pyuria with daily ingestion of 300 mL of cranberry juice cocktail (15.0% versus 28.1% in controls). However, subsequent studies of cranberries for prevention of UTI, including a large Cochrane meta-analysis, have shown mixed results. Various mechanisms of the bacteriologic effect of cranberries are postulated; however, inhibition of P fimbriae–mediated adhesion of E. coli by proanthocyanidin (PAC) remains the leading theory.
We sought to compare antibiotic susceptibility and proportions of non–E. coli Enterobacteriaceae among Gram-negative urinary isolates from participants randomized to cranberry capsules compared to placebo.

Characterization and comparison of phenolic composition, antioxidant capacity and instrumental taste profile of juices from different botanical origins

Posted: September 28, 2015
Authors: Granato D, Karnopp AR, van Ruth SM
Journal: J Sci Food Agric 95(10):1997-2006

Abstract: BACKGROUND: The European Union registered a consumption of about 10.7 billion litres of juices in 2011 and a great part of this amount is imported from other countries, which makes the monitoring of their quality essential. This work was aimed at mapping the quality of various juices from different botanical origins from instrumental taste, chemical marker and antioxidant capacity perspectives. It also characterized the individual phenolic composition of juices previously classified according to their antioxidant activity and total phenolic material level.
RESULTS: Overall, by using correlation analysis and chemometrics (HCA and PCA), data showed that total phenolics, specifically gallic acid, p-coumaric acid, anthocyanins, flavanols and flavonols, are the main contributors to the antioxidant activity. Elderberry and pomegranate juices presented the highest phenolic content and antioxidant activity. On the other hand, orange, apple and cranberry juices had the lowest levels of total phenolics and flavonoids, DPPH and CUPRAC.
CONCLUSION: The use of chemometrics coupled to ANOVA seems to be a suitable approach to evaluate the quality of fruit juices from different botanical origins. Additionally, the instrumental taste profile correlated well with the chemical composition and antioxidant capacity, showing its potential application in assessing the functionality of juices.

Chemical characterization and chemo-protective activity of cranberry phenolic powders in a model cell culture. Response of the antioxidant defenses and regulation of signaling pathways

Posted: September 28, 2015
Journal: Food Res Int 71:68-82

Abstract: Oxidative stress and reactive oxygen species (ROS)-mediated cell damage are implicated in various chronic pathologies. Emerging studies show that polyphenols may act by increasing endogenous antioxidant defense potential. Cranberry has one of the highest polyphenol content among commonly consumed fruits. In this study, the hepato-protective activity of a cranberry juice (CJ) and cranberry extract (CE) powders against oxidative stress was screened using HepG2 cells, looking at ROS production, intracellular non-enzymatic and enzymatic antioxidant defenses by reduced glutathione concentration (GSH), glutathione peroxidase (GPx) and glutathione reductase (GR) activity and lipid peroxidation biomarker malondialdehyde (MDA). Involvement of major protein kinase signaling pathways was also evaluated. Both powders in basal conditions did not affect cell viability but decreased ROS production and increased GPx activity, conditions that may place the cells in favorable conditions against oxidative stress. Powder pre-treatment of HepG2 cells for 20 h significantly reduced cell damage induced by 400 micro M tert-butylhydroperoxide (t-BOOH) for 2 h. Both powders (5-50 micro g/ml) reduced t-BOOH-induced increase of MDA by 20% (CJ) and 25% (CE), and significantly reduced over-activated GPx and GR. CE, with a significantly higher amount of polyphenols than CJ, prevented a reduction in GSH and significantly reduced ROS production. CJ reversed the t-BOOH-induced increase in phospho-c-Jun N-terminal kinase. This study demonstrates that cranberry polyphenols may help protect liver cells against oxidative insult by modulating GSH concentration, ROS and MDA generation, antioxidant enzyme activity and cell signaling pathways.

Comparative assessment of Cranberry and Chlorhexidine mouthwash on streptococcal colonization among dental students: A randomized parallel clinical trial.

Posted: September 28, 2015
Authors: Khairnar MR, Karibasappa GN, Dodamani AS, Vishwakarma P, Naik RG, Deshmukh MA
Journal: Contemp Clin Dent 6(1):35-9

Abstract: BACKGROUND: Chlorhexidine gluconate mouthwash has earned an eponym of the gold standard against oral infections, but with certain limitations. There is no effective alternative to Chlorhexidine. Cranberry is known to inhibit bacterial adhesion in various systemic infections and acts as a strong antioxidant. However, it is less explored for its dental use. Hence, there is a need to evaluate its effect against oral infections.
AIM: The aim was to compare the efficacy of 0.2% Chlorhexidine mouthwash with 0.6% Cranberry mouthwash on Streptococcus mutans.
MATERIALS AND METHODS: This was a double-blind, randomized parallel group clinical trial. Total sample of 50 subjects, aged 18-20 years, were randomly divided into two groups, Group A (25) and Group B (25) were given 10 mL of Chlorhexidine mouthwash and Cranberry mouthwash twice daily, respectively, for 14 days each. The plaque samples, which were taken from the subjects on 1(st) day and 14(th) day, were inoculated on blood agar plates and incubated at 37degreeC for 24-48 h. Number of streptococcal colony forming units were calculated using digital colony counter. The data were subjected to paired t-test and unpaired t-test at a 5% significance level.
RESULTS: (1) Chlorhexidine mouthwash showed 69% reduction whereas Cranberry mouthwash showed 68% reduction in S. mutans count. (2) No significant difference was seen between Chlorhexidine and Cranberry mouthwash on streptococci.
CONCLUSION: Cranberry mouthwash is equally effective as Chlorhexidine mouthwash with beneficial local and systemic effect. Hence, it can be used effectively as an alternative to Chlorhexidine mouthwash.

Comparative in vitro fermentations of cranberry and grape seed polyphenols with colonic microbiota.

Posted: September 28, 2015
Authors: Sanchez-Patan F, Barroso E, van de Wiele T, Jimenez-Giron A, Martin-Alvarez PJ, Moreno-Arribas MV, Martinez-Cuesta MC, Pelaez C, Requena T, Bartolome B
Journal: Food Chem 183:273-82,

Abstract: In this study, we have assessed the phenolic metabolism of a cranberry extract by microbiota obtained from the ascending colon and descending colon compartments of a dynamic gastrointestinal simulator (SHIME). For comparison, parallel fermentations with a grape seed extract were carried out. Extracts were used directly without previous intestinal digestion. Among the 60 phenolic compounds targeted, our results confirmed the formation of phenylacetic, phenylpropionic and benzoic acids as well as phenols such as catechol and its derivatives from the action of colonic microbiota on cranberry polyphenols. Benzoic acid (38.4mug/ml), 4-hydroxy-5-(3'-hydroxyphenyl)-valeric acid (26.2mug/ml) and phenylacetic acid (19.5mug/ml) reached the highest concentrations. Under the same conditions, microbial degradation of grape seed polyphenols took place to a lesser extent compared to cranberry polyphenols, which was consistent with the more pronounced antimicrobial effect observed for the grape seed polyphenols, particularly against Bacteroides, Prevotella and Blautia coccoides-Eubacterium rectale.

Cranberries (Oxycoccus quadripetalus) inhibit lipid metabolism and modulate leptin and adiponectin secretion in 3T3-L1 adipocytes

Posted: September 28, 2015
Authors: Kowalska K, Olejnik A, Rychlik J, Grajek W
Journal: Food Chem 185:383-8

Abstract: It has previously been shown that lyophilized cranberries (LCB) decreased lipid accumulation in 3T3-L1 cells and inhibited preadipocyte differentiation by down-regulation of the expression of key transcription factors (PPARgamma, C/EBPalpha, SREBP1) of the adipogenesis pathway. To elucidate the molecular basis of anti-lipogenic activity of LCB, the expression of several genes involved in lipid metabolism, such as adipocyte fatty acid-binding protein (aP2), lipoprotein lipase (LPL), fatty acid synthase (FAS), hormone sensitive lipase (HSL) and perilipin 1 (PLIN1), was examined in the present study. Additionally, the effects of LCB on adiponectin and leptin expression and protein secretion were also investigated. LCB reduced lipid accumulation during preadipocyte differentiation by down-regulation of the mRNA level of aP2, FAS, LPL, HSL and PLIN1. Moreover, LCB decreased leptin gene expression and increased adiponectin gene expression and protein secretion in a dose-dependent manner. Therefore cranberries could be considered as bioactive factors, which are effective in the inhibition of adipose tissue mass production.

Cranberry flavonoids prevent toxic rat liver mitochondrial damage in vivo and scavenge free radicals in vitro.

Posted: September 28, 2015
Authors: Lapshina EA, Zamaraeva M, Cheshchevik VT, Olchowik-Grabarek E, Sekowski S, Zukowska I, Golovach NG, Burd VN, Zavodnik IB
Journal: Cell Biochem Funct 33(4):202-10

Abstract: The present study was undertaken for further elucidation of the mechanisms of flavonoid biological activity, focusing on the antioxidative and protective effects of cranberry flavonoids in free radical-generating systems and those on mitochondrial ultrastructure during carbon tetrachloride-induced rat intoxication. Treatment of rats with cranberry flavonoids (7mg/kg) during chronic carbon tetrachloride-induced intoxication led to prevention of mitochondrial damage, including fragmentation, rupture and local loss of the outer mitochondrial membrane. In radical-generating systems, cranberry flavonoids effectively scavenged nitric oxide (IC50 =4.4+/-0.4micro g/ml), superoxide anion radicals (IC50 =2.8+/-0.3micro g/ml) and hydroxyl radicals (IC50 =53+/-4micro g/ml). The IC50 for reduction of 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH) was 2.2+/-0.3micro g/ml. Flavonoids prevented to some extent lipid peroxidation in liposomal membranes and glutathione oxidation in erythrocytes treated with UV irradiation or organic hydroperoxides as well as decreased the rigidity of the outer leaflet of the liposomal membranes. The hepatoprotective potential of cranberry flavonoids could be due to specific prevention of rat liver mitochondrial damage. The mitochondria-addressed effects of flavonoids might be related both to radical-scavenging properties and modulation of various mitochondrial events.

Cranberry fruit powder (Flowens™)improves lower urinary tract symptoms in men: a double-blind, randomized, placebo-controlled trial

Posted: September 28, 2015
Authors: Vidlar A, Student Jr V, Vostalova J, Fromentin E, Roller M, Simanek V, Student V
Journal: World J Urol DOI 10.1007/s00345-015-1611-7

Abstract: Lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia increase with age. To date, several medications are available to treat LUTS, including herbal remedies which offer less side effects but lack robust efficacy studies.
This 6-month, randomized, double-blind, placebo-controlled study aimed at evaluating the dose effect of 250 or 500 mg cranberry powder (Flowens™) on LUTS and uroflowmetry in men over the age of 45. A total of 124 volunteers with PSA levels <2.5 ng/mL and an international prostate symptoms score (IPSS) score &#8805;8 were recruited and randomized. The primary outcome measure was the IPSS, evaluated at 3 and 6 months. Secondary outcome measures included quality of life, bladder volume (Vol), maximum urinary flow rate (Q max), average urinary flow rate (Q ave), ultrasound-estimated post-void residual urine volume (PVR), serum prostate-specific antigen, selenium, interleukin 6, and C-reactive protein at 6 months.
After 6 months, subjects in both Flowens™ groups had a lower IPSS (-3.1 and -4.1 in the 250- and 500-mg groups, p = 0.05 and p < 0.001, respectively) versus the placebo group (-1.5), and a dose-response effect was observed. There were significant differences in Q max, Q ave, PVR, and Vol in the Flowens™ 500-mg group versus baseline (p < 0.05). A dose-dependent effect on Vol was observed, as well as on PVR, for participants with a nonzero PVR. There was no effect on clinical chemistry or hematology markers.
Flowens™ showed a clinically relevant, dose-dependent, and significant reduction in LUTS in men over 45.

Cranberry juice capsules and urinary tract infection after surgery: results of a randomized trial

Posted: September 28, 2015
Authors: Foxman B, Cronenwett AE, Spino C, Berger MB, Morgan DM
Journal: Am J Obstet Gynecol 213(2):194.e1-8

Abstract: OBJECTIVE: The risk of urinary tract infection (UTI) among women undergoing elective gynecological surgery during which a catheter is placed is high: 10-64% following catheter removal. We conducted the first randomized, double-blind, placebo-controlled trial of the therapeutic efficacy of cranberry juice capsules in preventing UTI after surgery.
STUDY DESIGN: We recruited patients from a single hospital between August 2011 and January 2013. Eligible participants were undergoing elective gynecological surgery that did not involve a fistula repair or vaginal mesh removal. One hundred sixty patients were randomized and received 2 cranberry juice capsules 2 times a day, equivalent to 2 8 ounce servings of cranberry juice, for 6 weeks after surgery or matching placebo. The primary endpoint was the proportion of participants who experienced clinically diagnosed and treated UTI with or without positive urine culture. Kaplan-Meier plots and log rank tests compared the 2 treatment groups.
RESULTS: The occurrence of UTI was significantly lower in the cranberry treatment group compared with the placebo group (15 of 80 [19%] vs 30 of 80 [38%]; odds ratio, 0.38; 95% confidence interval, 0.19-0.79; P = .008). After adjustment for known confounders, including the frequency of intermittent self-catheterization in the postoperative period, the protective effects of cranberry remained (odds ratio, 0.42; 95% confidence interval, 0.18-0.94). There were no treatment differences in the incidence of adverse events, including gastrointestinal upset (56% vs 61% for cranberry vs placebo).
CONCLUSION: Among women undergoing elective benign gynecological surgery involving urinary catheterization, the use of cranberry extract capsules during the postoperative period reduced the rate of UTI by half.

Cranberry juice consumption lowers markers of cardiometabolic risk, including blood pressure and circulating C-reactive protein, triglyceride, and glucose concentrations in adults

Posted: September 28, 2015
Authors: Novotny JA, Baer DJ, Khoo C, Gebauer SK, Charron CS
Journal: J Nutr 145(6):1185-93

Abstract: BACKGROUND: Cardiometabolic risk is the risk of cardiovascular disease (CVD), diabetes, or stroke, which are leading causes of mortality and morbidity worldwide.
OBJECTIVE: The objective of this study was to determine the potential of low-calorie cranberry juice (LCCJ) to lower cardiometabolic risk.
METHODS: A double-blind, placebo-controlled, parallel-arm study was conducted with controlled diets. Thirty women and 26 men (mean baseline characteristics: 50 y; weight, 79 kg; body mass index, 28 kg/m(2)) completed an 8-wk intervention with LCCJ or a flavor/color/energy-matched placebo beverage. Twice daily volunteers consumed 240 mL of LCCJ or the placebo beverage, containing 173 or 62 mg of phenolic compounds and 6.5 or 7.5 g of total sugar per 240-mL serving, respectively.
RESULTS: Fasting serum triglycerides (TGs) were lower after consuming LCCJ and demonstrated a treatment x baseline interaction such that the participants with higher baseline TG concentrations were more likely to experience a larger treatment effect (1.15 +/- 0.04 mmol/L vs. 1.25 +/- 0.04 mmol/L, respectively; P = 0.027). Serum C-reactive protein (CRP) was lower for individuals consuming LCCJ than for individuals consuming the placebo beverage [ln transformed values of 0.522 +/- 0.115 ln(mg/L) vs. 0.997 +/- 0.120 ln(mg/L), P = 0.0054, respectively, and equivalent to 1.69 mg/L vs. 2.71 mg/L back-transformed]. LCCJ lowered diastolic blood pressure (BP) compared with the placebo beverage (69.2 +/- 0.8 mm Hg for LCCJ vs. 71.6 +/- 0.8 mm Hg for placebo; P = 0.048). Fasting plasma glucose was lower (P = 0.03) in the LCCJ group (5.32 +/- 0.03 mmol/L) than in the placebo group (5.42 +/- 0.03 mmol/L), and LCCJ had a beneficial effect on homeostasis model assessment of insulin resistance for participants with high baseline values (P = 0.035).
CONCLUSION: LCCJ can improve several risk factors of CVD in adults, including circulating TGs, CRP, and glucose, insulin resistance, and diastolic BP. This trial was registered at clinicaltrials.gov as NCT01295684.

Cranberry supplementation in the prevention of non-severe lower urinary tract infections: a pilot study.

Posted: September 28, 2015
Authors: Ledda A, Bottari A, Luzzi R, Belcaro G, Hu S, Dugall M, Hosoi M, Ippolito E, Corsi M, Gizzi G, Morazzoni P, Riva A, Giacomelli L, Togni S
Journal: Eur Rev Med Pharmacol Sci 19(1):77-80,

Abstract: OBJECTIVE: Cranberry extracts have been tested as a nutritional supplementation in the prevention of recurrent lower-urinary tract infections (R-UTIs), with mixed results. This pilot, registry study evaluates the prophylactic effects of oral supplementation with a new well-standardized cranberry extract in patients with R-UTI, over a 2-month follow-up.
PATIENTS AND METHODS: All subjects were suggested to take one capsule containing a cranberry extract (AnthocranTM) for 60 days and were also given lifestyle advice. Clinical outcomes were compared between patients on cranberry extracts and those who don't take this supplementation.
RESULTS: In total, 22 subjects completed the study in each of the two groups. In the cranberry group, the reduction in the frequency of UTI episodes during the study period compared with the two months before the inclusion was 73.3% (p < 0.05). This figure was 15.4% in the control group (p < 0.05; p = 0.012 vs cranberry group). Seven (31.8%) subjects in the cranberry group were symptom-free; no patient was symptom-free in the control group (p < 0.05). The mean duration of UTI episodes was 2.5 +/- 1.3 days in the cranberry group, compared with 3.6 +/- 1.7 days in subjects not on cranberry (p < 0.05). Three subjects (13.6%) in the cranberry group and 8 (36.3%) in the control group required medical consultation for UTI symptoms (p < 0.05). Urine evaluation was completely negative in 20/22 subjects in the Cranberry group (90.9%) and in 11 control subjects (50.0%; p < 0.005). No adverse events were observed.
CONCLUSIONS: These preliminary results, obtained in a field-practice setting, indicates the effectiveness and safety of a well-standardized cranberry extract in the prevention of R-UTI.

Cranberry Xyloglucan Structure and Inhibition of Escherichia coli Adhesion to Epithelial Cells.

Posted: September 28, 2015
Authors: Hotchkiss AT Jr, Nunez A, Strahan GD, Chau HK, White AK, Marais JP, Hom K, Vakkalanka MS, Di R, Yam KL, Khoo C
Journal: J Agric Food Sci 63(23):5622-33

Abstract: Cranberry juice has been recognized as a treatment for urinary tract infections on the basis of scientific reports of proanthocyanidin anti-adhesion activity against Escherichia coli as well as from folklore. Xyloglucan oligosaccharides were detected in cranberry juice and the residue remaining following commercial juice extraction that included pectinase maceration of the pulp. A novel xyloglucan was detected through tandem mass spectrometry analysis of an ion at m/z 1055 that was determined to be a branched, three hexose, four pentose oligosaccharide consistent with an arabino-xyloglucan structure. Two-dimensional nuclear magnetic resonance spectroscopy analysis provided through-bond correlations for the alpha-l-Araf (1->2) alpha-d-Xylp (1->6) beta-d-Glcp sequence, proving the S-type cranberry xyloglucan structure. Cranberry xyloglucan-rich fractions inhibited the adhesion of E. coli CFT073 and UTI89 strains to T24 human bladder epithelial cells and that of E. coli O157:H7 to HT29 human colonic epithelial cells. SSGG xyloglucan oligosaccharides represent a new cranberry bioactive component with E. coli anti-adhesion activity and high affinity for type 1 fimbriae.

Depolymerisation optimisation of cranberry procyanidins and transport of resultant oligomers on monolayers of human intestinal epithelial Caco-2 cells

Posted: September 28, 2015
Authors: Ou K, Gu L
Journal: Food Chem 167:45-51

Abstract: Procyanidins in cranberries are predominantly polymers (>85%). The objective of this study was to optimise the depolymerisation of polymers and to investigate the absorption of resultant oligomers on Caco-2 cell monolayers. Depolymerisation conditions were optimised using response surface methodology. Depolymerisation, with or without added epicatechin, yielded 644 mug and 202 mug of oligomers (monomer through tetramers) per mg of partially purified polymers (PP), respectively. Oligomers (yielded from both methods) were transported through Caco-2 cell monolayer despite absorption rates being low. With the aid of response surface methodology, the optimum depolymerisation conditions were determined to be 60degreeC, 0.1M HCl in methanol and 3h without added epicatechin. The predicted maximum yield was 364 mug oligomers per mg of PP. The optimum depolymerisation condition with added epicatechin shared the same temperature, acid concentration and reaction time, in addition to an epicatechin/PP mass ratio of 2.19. Its predicted maximum oligomer yield was 1,089 mug/mg. The predicted yields were verified by experimental data.

Effect of high-molecular-weight component of Cranberry on plaque and salivary Streptococcus mutans counts in children: an in vivo study.

Posted: September 28, 2015
Authors: Gupta A, Bansal K, Marwaha M
Journal: J Indian Soc Pedod Prev Dent 33(2):128-33

Abstract: BACKGROUND: Previous investigations showed that a high-molecular-weight, nondialyzable material (NDM) from cranberries inhibits the adhesion of a number of bacterial species and prevents the coaggregation of many oral bacterial pairs.
AIM: In the present study, the effect of mouthrinse containing high-molecular-weight component of cranberry was evaluated on colonization of Streptococcus mutans in children and compared it with a control mouthrinse without high-molecular-weight component on Streptococcus mutans counts.
MATERIALS AND METHODS: A high-molecular-weight NDM was isolated from cranberry juice concentrate after the dialysis of the cranberry concentrate; followed by lyophilization. A mouthwash was prepared especially for the study having NDM in the concentration of 3 mg/ml. Following 4 weeks of daily usage of cranberry-containing mouthwash by the children of an experimental group (n = 20), the Streptococcus mutans counts in plaque and saliva were compared with that in control group using placebo mouthwash (n = 20) with the help of Dentocult SM strips.
RESULTS: There was a highlysignificant reduction in Streptococcus mutans counts in saliva and plaque of children using mouthwash containing cranberry NDM (P < 0.05) compared to control.
CONCLUSION: The data suggest that the high-molecular-weight cranberry extract in mouthwash has a significant potential in reducing the Streptococcus counts in the oral environment.

Effects of Proanthocyanidins on Adhesion, Growth, and Virulence of Highly Virulent Extraintestinal Pathogenic Escherichia coli Argue for Its Use to Treat Oropharyngeal Colonization and Prevent Ventilator-Associated Pneumonia.

Posted: September 28, 2015
Authors: Margetis D, Roux D, Gaudry S, Messika J, Bouvet O, Branger C, Ponnuswamy P, Oufella HA, Dreyfuss D, Denamur E, Ricard JD
Journal: Crit Care Med 43(6):e170-8,

Abstract: OBJECTIVE: In the context of increasing microbial resistance and limited new antimicrobials, we aimed to study the antimicrobial effects of cranberry proanthocyanidin extracts on Escherichia coli growth, adhesion to epithelial cells, and lung infection.
DESIGN: Experimental in vitro and in vivo investigation.
SETTING: University research laboratory.
SUBJECTS: Seventy-eight 6- to 8-week-old male Balb/C mice.
INTERVENTIONS: In vitro, the effect of increasing concentrations of cranberry proanthocyanidin on bacterial growth of different clinical E. coli isolates was evaluated. Ex vivo, adhesion of E. coli to fresh human buccal epithelial cells was measured in the presence or absence of cranberry proanthocyanidin using microscopy. In vivo, lung bacterial count, pulmonary immune response (neutrophil murine chemokine keratinocyte-derived cytokine measurement and polymorphonuclear recruitment in bronchoalveolar lavage fluid), and lethality were evaluated in a pneumonia mouse model with E. coli precultured with or without cranberry proanthocyanidin. E. coli isolates originated from ventilated ICU patients with respiratory tract colonization or ventilator- associated pneumonia. They differed in number of virulence genes.
MEASUREMENTS AND MAIN RESULTS: A significant inhibition of bacterial growth was observed with increasing concentration of cranberry proanthocyanidin, affecting both time to maximal growth and maximal growth rate (p<0.0001 for both). The minimal concentration at which this effect occurred was 250 mug/mL. Cranberry proanthocyanidin significantly reduced E. coli adhesion to fresh buccal epithelial cells by up to 80% (p<0.001). Bacterial counts in homogenized lungs and bronchoalveolar lavage fluid were decreased after cranberry proanthocyanidin exposition (p<0.05 and p<0.01, respectively). Cranberry proanthocyanidin also decreased KC concentrations and polymorphonuclear cell recruitment in bronchoalveolar lavage fluid (p<0.05 for both). At identical inoculum, mortality was reduced by more than half in mice inoculated with E. coli exposed to cranberry proanthocyanidin (p<0.01).
CONCLUSION: Cranberry proanthocyanidins exhibit potent effects on growth, adhesion, and virulence of oropharyngeal and lung isolates of E. coli, suggesting that cranberry proanthocyanidin could be of clinical interest to reduce oropharyngeal colonization and prevent lung infection.

Flavonoids and phenolic acids from cranberry juice are bioavailable and bioactive in healthy older adults

Posted: September 28, 2015
Authors: McKay DL, Chen CY, Zampariello CA, Blumberg JB
Journal: Food Chem 168:233-40

Abstract: Cranberries (Vaccinium macrocarpon) are a rich source of phenolic phytochemicals, which likely contribute to their putative health benefits. A single-dose pharmacokinetic trial was conducted in 10 healthy adults 50y to evaluate the acute (24-h) absorption and excretion of flavonoids, phenolic acids and proanthocyanidins (PACs) from a low-calorie cranberry juice cocktail (54% juice). Inter-individual variability was observed in the Cmax and Tmax of many of these compounds in both plasma and urine. The sum total concentration of phenolics detected in plasma reached a peak of 34.2mug/ml between 8 and 10h, while in urine this peak was 269.8mug/mg creatinine, and appeared 2-4h earlier. The presence of PAC-A2 dimers in human urine has not previously been reported. After cranberry juice consumption, plasma total antioxidant capacity assessed using ORAC and TAP assays correlated with individual metabolites. Our results show phenolic compounds in cranberry juice are bioavailable and exert antioxidant actions in healthy older adults.

Great heterogeneity of commercial fruit juices to induce endothelium-dependent relaxations in isolated porcine coronary arteries: role of the phenolic content and composition.

Posted: September 28, 2015
Authors: Auger C, Pollet B, Arnold C, Marx C, Schini-Kerth VB
Journal: J Med Food 18(1):128-36

Abstract: Since polyphenol-rich products such as red wine, grape juice, and grape extracts have been shown to induce potent endothelium-dependent relaxations, we have evaluated whether commercial fruit juices such as those from berries are also able to induce endothelium-dependent relaxations of isolated coronary arteries and, if so, to determine whether this effect is related to their phenolic content. Among the 51 fruit juices tested, 2/12 grape juices, 3/7 blackcurrant juices, 4/5 cranberry juices, 1/6 apple juices, 0/5 orange juices, 2/6 red fruit and berry juices, 3/6 blends of red fruit juices, and 0/4 non-red fruit juices were able to induce relaxations achieving more than 50% at a volume of 1%. The active fruit juices had phenolic contents ranging from 0.31 to 1.86g GAE/L, which were similar to those of most of the less active juices with the exception of one active grape juice (2.14g GAE/L) and one active blend of red fruit juices (3.48g GAE/L). Altogether, these findings indicate that very few commercial fruit juices have the ability to induce potent endothelium-dependent relaxations, and that this effect is not related to their quantitative phenolic content, but rather to their qualitative phenolic composition.

Green tea polyphenol epigallocatechin-3-gallate and cranberry proanthocyanidins act in synergy with cathelicidin (LL-37) to reduce the LPS-induced inflammatory response in a three-dimensional co-culture model of gingival epithelial cells and fibroblasts.

Posted: September 28, 2015
Authors: Lombardo Bedran TB, Palomari Spolidorio D, Grenier D
Journal: Arch Oral Biol 60(6):845-53

Abstract: OBJECTIVES: The human antimicrobial peptide cathelicidin (LL-37) possesses anti-inflammatory properties that may contribute to attenuating the inflammatory process associated with chronic periodontitis. Plant polyphenols, including those from cranberry and green tea, have been reported to reduce inflammatory cytokine secretion by host cells. In the present study, we hypothesized that A-type cranberry proanthocyanidins (AC-PACs) and green tea epigallocatechin-3-gallate (EGCG) act in synergy with LL-37 to reduce the secretion of inflammatory mediators by oral mucosal cells.
METHODS: A three-dimensional (3D) co-culture model of gingival epithelial cells and fibroblasts treated with non-cytotoxic concentrations of AC-PACs (25 and 50 mug/ml), EGCG (1 and 5 mug/ml), and LL-37 (0.1 and 0.2 muM) individually and in combination (AC-PACs+LL-37 and EGCG+LL-37) were stimulated with Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS). Multiplex ELISA assays were used to quantify the secretion of 54 host factors, including chemokines, cytokines, growth factors, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs).
RESULTS: LL-37, AC-PACs, and EGCG, individually or in combination, had no effect on the regulation of MMP and TIMP secretion but inhibited the secretion of several cytokines. AC-PACs and LL-37 acted in synergy to reduce the secretion of CXC-chemokine ligand 1 (GRO-alpha), granulocyte colony-stimulating factor (G-CSF), and interleukin-6 (IL-6), and had an additive effect on reducing the secretion of interleukin-8 (IL-8), interferon-gamma inducible protein 10 (IP-10), and monocyte chemoattractant protein-1 (MCP-1) in response to LPS stimulation. EGCG and LL-37 acted in synergy to reduce the secretion of GRO-alpha, G-CSF, IL-6, IL-8, and IP-10, and had an additive effect on MCP-1 secretion.
CONCLUSION: The combination of LL-37 and natural polyphenols from cranberry and green tea acted in synergy to reduce the secretion of several cytokines by an LPS-stimulated 3D co-culture model of oral mucosal cells. Such combinations show promising results as potential adjunctive therapies for treating inflammatory periodontitis.Copyright © 2015 Elsevier Ltd. All rights reserved.

In vivo and in vitro antibacterial activities of cranberry extract against E. coli O157:H7 in urinary tract infected rats.

Posted: September 28, 2015
Authors: Ibrahim OMS, Sarhan SR, Hameed AA
Journal: Adv Anim Vet Sci 3(4):233-244

Abstract: The objective of this study was to determine the in-vitro and in-vivo activity of cranberry extracts against Escherichia coli O157:H7. This strain of E. coli was the most common etiologic agent of urinary tract infections isolated from patients. Filter sterilized aqueous and methanol extract of cranberry was prepared and used in the present study. The aqueous extract of cranberry produced inhibition zone ranging from (10.8-23.8) mm against the tested bacteria. While the methanol extract produces larger zones of inhibition (12.1-24.2) mm against the bacteria. The minimum inhibitory concentration (MIC) for the methanol and aqueous extract was 0.35 and 0.625 mg/ml, respectively. In vivo study involved inducing UTI in rats and then treated with (200 mg/kg B.W) aqueous and methanol extract and compared with Gentamicin treatment at a dose of (2 mg/kg B.W) subcutaneously for 14 days. Methanol extract succeeded in treated UTI caused by Escherichia coli in the infected rats and prevented infection comparing with aqueous extract and Gentamicin. Food, water intake, body weight, pH and creatinine level returned to normal values after treatment with methanol extract of Cranberry fruit (200 mg/Kg.B.W) comparing with aqueous extract of Cranberry fruit and 2 mg/Kg.B.W. of Gentamicin. These parameters used in this current study as indicator for curing from infection. These findings indicated that cranberry extract was effective at all levels in inhibiting E. coli O157:H7; thus it possesses antimicrobial activity and hold great promise as an antimicrobial agent.

Methods to determine effects of cranberry proanthocyanidins on extraintestinal infections: Relevance for urinary tract health.

Posted: September 28, 2015
Authors: Feliciano RP, Krueger CG, Reed JD
Journal: Mol Nutr Food Res 59(7):1292-306,

Abstract: Urinary tract infections (UTI) are one of the most frequent extraintestinal infections caused by Escherichia coli (ExPEC). Cranberry juice has been used for decades to alleviate symptoms and prevent recurrent UTI. The putative compounds in cranberries are proanthocyanidins (PAC), specifically PAC with "A-type" bonds. Since PAC are not absorbed, their health benefits in UTI may occur through interactions at the mucosal surface in the gastrointestinal tract. Recent research showed that higher agglutination of ExPEC and reduced bacterial invasion are correlated with higher number of "A-type" bonds and higher degree of polymerization of PAC. An understanding of PAC structure-activity relationship is becoming feasible due to advancements, not only in obtaining purified PAC fractions that allow accurate estimation, but also in high-resolution MS methodologies, specifically, MALDI-TOF MS. A recent MALDI-TOF MS deconvolution method allows quantification of the ratios of "A-type" to "B-type" bonds enabling characteristic fingerprints. Moreover, the generation of fluorescently labeled PAC allows visualization of the interaction between ExPEC and PAC with microscopy. These tools can be used to establish structure-activity relationships between PAC and UTI and give insight on the mechanism of action of these compounds in the gut without being absorbed.

Phenol antioxidant quantity and quality in foods: fruits

Posted: September 28, 2015
Authors: Vinson JA, Su X, Zubik L, Bose P
Journal: J Agric Food Chem 49(11):5315-21

Abstract: The free and bound phenols have been measured in 20 fruits commonly consumed in the American diet. Phenols were measured colorimetrically using the Folin-Ciocalteu reagent with catechin as the standard after correction for ascorbic acid contribution. On a fresh weight basis, cranberry had the highest total phenols, and was distantly followed by red grape. Free and total phenol quality in the fruits was analyzed by using the inhibition of lower density lipoprotein oxidation promoted by cupric ion. Ascorbate had only a minor contribution to the antioxidants in fruits with the exception of melon, nectarine, orange, white grape, and strawberry. The fruit extracts' antioxidant quality was better than the vitamin antioxidants and most pure phenols, suggesting synergism among the antioxidants in the mixture. Using our assay, fruits had significantly better quantity and quality of phenol antioxidants than vegetables. Fruits, specifically apples and cranberries, have phenol antioxidants that can enrich lower density lipoproteins and protect them from oxidation. The average per capita consumption of fruit phenols in the U.S. is estimated to be 255 mg/day of catechin equivalents.

Prevention of oxidative stress, inflammation and mitochondrial dysfunction in the intestine by different cranberry phenolic fractions

Posted: September 28, 2015
Authors: Denis MC, Desjardins Y, Furtos A, Marcil V, Dudonne S, Montoudis A, Garofalo C, Delvin E, Marette A, Levy E
Journal: Clinical Science 128(3):197-212

Abstract: Cranberry fruit has been reported to have high antioxidant effectiveness that is potentially linked to its richness in diversified polyphenolic content. The aim of the present study was to determine the role of cranberry polyphenolic fractions in oxidative stress (OxS), inflammation and mitochondrial functions using intestinal Caco-2/15 cells. The combination of HPLC and UltraPerformance LC-tandem quadrupole (UPLC-TQD) techniques allowed us to characterize the profile of low, medium and high molecular mass polyphenolic compounds in cranberry extracts. The medium molecular mass fraction was enriched with flavonoids and procyanidin dimers whereas procyanidin oligomers (DP > 4) were the dominant class of polyphenols in the high molecular mass fraction. Pre-incubation of Caco-2/15 cells with these cranberry extracts prevented iron/ascorbate-mediated lipid peroxidation and counteracted lipopolysaccharide-mediated inflammation as evidenced by the decrease in pro-inflammatory cytokines (TNF-alpha and interleukin-6), cyclo-oxygenase-2 and prostaglandin E2. Cranberry polyphenols (CP) fractions limited both nuclear factor kappaB activation and Nrf2 down-regulation. Consistently, cranberry procyanidins alleviated OxS-dependent mitochondrial dysfunctions as shown by the rise in ATP production and the up-regulation of Bcl-2, as well as the decline of protein expression of cytochrome c and apoptotic-inducing factor. These mitochondrial effects were associated with a significant stimulation of peroxisome-proliferator-activated receptor gamma co-activator-1-alpha, a central inducing factor of mitochondrial biogenesis and transcriptional co-activator of numerous downstream mediators. Finally, cranberry procyanidins forestalled the effect of iron/ascorbate on the protein expression of mitochondrial transcription factors (mtTFA, mtTFB1, mtTFB2). Our findings provide evidence for the capacity of CP to reduce intestinal OxS and inflammation while improving mitochondrial dysfunction.

Preventive effects of cranberry products on experimental colitis induced by dextran sulphate sodium in mice

Posted: September 28, 2015
Authors: Xiao X, Kim J, Sun Q, Kim D, Park CS, Lu TS, Park Y
Journal: Food Chem 167:438-46

Abstract: With the prevalence of inflammatory bowel disease (IBD) and its associated risk for development of colorectal cancer, it is of great importance to prevent and treat IBD. However, due to the complexity of etiology and potentially serious adverse effects, treatment options for IBD are relatively limited. Thus, the purpose of this study was to identify a safe food-based approach for the prevention and treatment of IBD. In this study, we tested the effects of cranberry products on preventing dextran sulphate sodium-induced murine colitis. Our results suggest that both cranberry extract and dried cranberries-fed groups had a significantly reduced disease activity index, where dried cranberries were more effective in preventing colitis than cranberry extract. Shortening of colon length, colonic myeloperoxidase activity and production of pro-inflammatory cytokines were attenuated in animals fed dried cranberries compared to the controls. The current report suggests that cranberries can be applied to prevent and reduce the symptoms of IBD.

Standardized cranberry capsules for radiation cystitis in prostate cancer patients in New Zealand: a randomized double blinded, placebo controlled pilot study

Posted: September 28, 2015
Authors: Hamilton K, Bennett NC, Purdie G, Herst PM
Journal: Support Care Cancer 23(1):95-102

Abstract: PURPOSE: Acute radiation cystitis, inflammation of the bladder, is a common side effect in men receiving external beam radiation for prostate cancer. Although several treatments provide symptomatic relief, there is no effective treatment to prevent or treat radiation cystitis. Cranberry products have been associated with urinary tract health. This study aimed to determine the effect of highly standardized cranberry capsules (containing 72 mg proanthocyanidins [PACS]) compared with that of placebo capsules on the incidence and severity of radiation cystitis.
METHODS: Forty-one men with prostate cancer participated in a double blinded randomized placebo controlled study. Men took one capsule a day at breakfast during treatment and for 2 weeks after treatment completion. Severity of urinary symptoms and the bother these caused were measured using the individual items of the urinary domain of the Modified Expanded Prostate Index Composite (EPIC).
RESULTS: The incidence of cystitis was lower in men taking cranberry capsules (65%) compared with those that took placebo capsules (90%) (p=0.058); severe cystitis was seen in 30% of men in the cranberry arm and 45% in the placebo arm (p=0.30). Overall, the incidence of pain/burning was significantly lower in the cranberry cohort (p=0.045). Men on the low hydration regimen who took cranberry had less pain/burning (p=0.038), stronger urine steam (p=0.030) and used significantly fewer pads/liners (p=0.042), which was significantly different from those on the high hydration regimen (p=0.028).
CONCLUSION: Men receiving radiation therapy for prostate cancer may benefit from using cranberry capsules, particularly those on low hydration regimens or with baseline urinary symptoms.

The cranberry flavonoids PAC DP-9 and quercetin aglycone induce cytotoxicity and cell cycle arrest and increase cisplatin sensitivity in ovarian cancer cells.

Posted: September 28, 2015
Authors: Wang Y, Han A, Chen E, Singh RK, Chichester CO, Moore RG, Singh AP, Vorsa N
Journal: Int J Oncol 46(5):1924-34

Abstract: Cranberry flavonoids (flavonols and flavan-3-ols), in addition to their antioxidant properties, have been shown to possess potential in vitro activity against several cancers. However, the difficulty of isolating cranberry compounds has largely limited anticancer research to crude fractions without well-defined compound composition. In this study, individual cranberry flavonoids were isolated to the highest purity achieved so far using gravity and high performance column chromatography and LC-MS characterization. MTS assay indicated differential cell viability reduction of SKOV-3 and OVCAR-8 ovarian cancer cells treated with individual cranberry flavonoids. Treatment with quercetin aglycone and PAC DP-9, which exhibited the strongest activity, induced apoptosis, led to caspase-3 activation and PARP deactivation, and increased sensitivity to cisplatin. Furthermore, immunofluorescence microscopy and western blot study revealed reduced expression and activation of epidermal growth factor receptor (EGFR) in PAC DP-9 treated SKOV-3 cells. In addition, quercetin aglycone and PAC DP-9 deactivated MAPK-ERK pathway, induced downregulation of cyclin D1, DNA-PK, phospho-histone H3 and upregulation of p21, and arrested cell cycle progression. Overall, this study demonstrates promising in vitro cytotoxic and anti-proliferative properties of two newly characterized cranberry flavonoids, quercetin aglycone and PAC DP-9, against ovarian cancer cells.

A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice.

Posted: April 1, 2015
Authors: Anhê FF, Roy D, Pilon G, Dudonné S, Matamoros S, Varin TV, Garofalo C, Moine Q, Desjardins Y, Levy E, Marette A
Journal: Gut pii: gutjnl-2014-307142

Abstract: OBJECTIVE: The increasing prevalence of obesity and type 2 diabetes (T2D) demonstrates the failure of conventional treatments to curb these diseases. The gut microbiota has been put forward as a key player in the pathophysiology of
diet-induced T2D. Importantly, cranberry (Vaccinium macrocarpon Aiton) is associated with a number of beneficial health effects. We aimed to investigate the metabolic impact of a cranberry extract (CE) on high fat/high sucrose (HFHS)-fed mice and to determine whether its consequent antidiabetic effects are related to modulations in the gut microbiota.
DESIGN: C57BL/6J mice were fed either a chow or a HFHS diet. HFHS-fed mice were gavaged daily either with vehicle (water) or CE (200&#8197;mg/kg) for 8&#8197;weeks. The composition of the gut microbiota was assessed by analysing 16S rRNA gene
sequences with 454 pyrosequencing.
RESULTS: CE treatment was found to reduce HFHS-induced weight gain and visceral obesity. CE treatment also decreased liver weight and triglyceride accumulation in association with blunted hepatic oxidative stress and inflammation. CE
administration improved insulin sensitivity, as revealed by improved insulin tolerance, lower homeostasis model assessment of insulin resistance and decreased glucose-induced hyperinsulinaemia during an oral glucose tolerance test. CE treatment was found to lower intestinal triglyceride content and to alleviate intestinal inflammation and oxidative stress. Interestingly, CE treatment markedly increased the proportion of the mucin-degrading bacterium Akkermansia in
our metagenomic samples.
CONCLUSIONS: CE exerts beneficial metabolic effects through improving HFHS
diet-induced features of the metabolic syndrome, which is associated with a
proportional increase in Akkermansia spp. population.

Cranberry extract standardized for proanthocyanidins promotes the immune response of Caenorhabditis elegans to Vibrio cholerae through the p38 MAPK pathway and HSF-1.

Posted: April 1, 2015
Authors: Dinh J, Angeloni JT, Pederson DB, Wang X, Cao M, Dong Y
Journal: PLoS One 9(7):e103290.

Abstract: Botanicals are rich in bioactive compounds, and some offer numerous beneficial effects to animal and human health when consumed. It is well known that phytochemicals in cranberries have anti-oxidative and antimicrobial activities. Recently, an increasing body of evidence has demonstrated that cranberry
phytochemicals may have potential benefits that promote healthy aging. Here, we use Caenorhabditis elegans as a model to show that water-soluble cranberry extract standardized to 4.0% proanthocyanidins (WCESP), a major component of
cranberries, can enhance host innate immunity to resist against Vibrio cholerae (V. cholerae; wild type C6706 (O1 El Tor biotype)) infection. Supplementation of WCESP did not significantly alter the intestinal colonization of V. cholerae, but
upregulated the expression of C. elegans innate immune genes, such as clec-46, clec-71, fmo-2, pqn-5 and C23G10.1. Additionally, WCESP treatment did not affect the growth of V. cholerae and expression of the major bacterial virulence genes, and only slightly reduced bacterial colonization within C. elegans intestine. These findings indicate that the major components of WCESP, including proanthocyanidins (PACs), may play an important role in enhancing the host innate
immunity. Moreover, we engaged C. elegans mutants and identified that the p38 MAPK signaling, insulin/IGF-1 signaling (IIS), and HSF-1 play pivotal roles in the WCESP-mediated host immune response. Considering the level of conservation between the innate immune pathways of C. elegans and humans, the results of this study suggest that WCESP may also play an immunity-promoting role in higher order organisms.

Cranberry proanthocyanidins have anti-biofilm properties against Pseudomonas aeruginosa.

Posted: April 1, 2015
Authors: Ulrey RK, Barksdale SM, Zhou W, van Hoek ML
Journal: BMC Complement Altern Med 14:499.

Abstract: BACKGROUND: Bacteria within a biofilm are phenotypically more resistant to antibiotics, desiccation, and the host immune system, making it an important virulence factor for many microbes. Cranberry juice has long been used to prevent
infections of the urinary tract, which are often related to biofilm formation. Recent studies have found that the A-type proanthocyanidins from cranberries have anti-biofilm properties against Escherichia coli.
METHODS: Using crystal violet biofilm staining, resazurin metabolism assays, and confocal imaging, we examined the ability of A-type proanthocyanidins (PACs) to disrupt the biofilm formation of Pseudomonas aeruginosa. We used mass spectrometry to analyze the proteomic effects of PAC treatment. We also performed synergy assays and in vitro and in vivo infections to determine whether PACs, alone and in combination with gentamicin, could contribute to the killing of P. aeruginosa and the survival of cell lines and G. mellonella. RESULTS: Cranberry PACs reduced P. aeruginosa swarming motility. Cranberry PACs significantly disrupted the biofilm formation of P. aeruginosa. Proteomics analysis revealed significantly different proteins expressed following PAC treatment. In addition, we found that PACs potentiated the antibiotic activity of gentamicin in an in vivo model of infection using G. mellonella. CONCLUSIONS: Results suggest that A-type proanthocyanidins may be a useful therapeutic against the biofilm-mediated infections caused by P. aeruginosa and
should be further tested.

Cranberry versus placebo in the prevention of urinary infections in multiple sclerosis: a multicenter, randomized, placebo-controlled, double-blind trial.

Posted: April 1, 2015
Authors: Gallien P, Amarenco G, Benoit N, Bonniaud V, Donzé C, Kerdraon J, de Seze M, Denys P, Renault A, Naudet F, Reymann JM.
Journal: Mult Scler 20(9):1252-1259.

Abstract: OBJECTIVE: Our aim was to assess the usefulness of cranberry extract in multiple sclerosis (MS) patients suffering from urinary disorders.
METHODS: In total, 171 adult MS outpatients with urinary disorders presenting at eight centers were randomized (stratification according to center and use of clean intermittent self-catheterization) to cranberry versus placebo in a 1-year,
prospective, double-blind study that was analyzed using a sequential method on an intent-to-treat basis. An independent monitoring board analyzed the results of the analyses each time 40 patients were assessed on the main endpoint. Cranberry extract (36 mg proanthocyanidins per day) or a matching placebo was taken by participants twice daily for 1 year. The primary endpoint was the time to first symptomatic urinary tract infection (UTI), subject to validation by a validation committee.
RESULTS: The second sequential analyses allowed us to accept the null hypothesis (no difference between cranberry and placebo). There was no difference in time to first symptomatic UTI distribution across 1 year, with an estimated hazard ratio
of 0.99, 95% CI [0.61, 1.60] (p = 0.97). Secondary endpoints and tolerance did not differ between groups.
CONCLUSION: Taking cranberry extract versus placebo twice a day did not prevent UTI occurrence in MS patients with urinary disorders. Trial Registration NCT00280592.

Effect of standardized cranberry extract on the activity and expression of selected biotransformation enzymes in rat liver and intestine.

Posted: April 1, 2015
Authors: Bártíková H, Boušová I, Jedli&#269;ková P, Ln&#283;ni&#269;ková K, Skálová L, Szotáková B
Journal: Molecules 19(9):14948-60.

Abstract: The use of dietary supplements containing cranberry extract is a common way to prevent urinary tract infections. As consumption of these supplements containing a mixture of concentrated anthocyanins and proanthocyanidins has increased, interest in their possible interactions with drug-metabolizing enzymes has grown. In this in vivo study, rats were treated with a standardized cranberry extract
(CystiCran®) obtained from Vaccinium macrocarpon in two dosage schemes (14 days, 0.5 mg of proanthocyanidins/kg/day; 1 day, 1.5 mg of proanthocyanidins/kg/day). The aim of this study was to evaluate the effect of anthocyanins and proanthocyanidins contained in this extract on the activity and expression of
intestinal and hepatic biotransformation enzymes: cytochrome P450 (CYP1A1, CYP1A2, CYP2B and CYP3A), carbonyl reductase 1 (CBR1), glutathione-S-transferase (GST) and UDP-glucuronosyl transferase (UGT). Administration of cranberry extract led to moderate increases in the activities of hepatic CYP3A (by 34%), CYP1A1 (by 38%), UGT (by 40%), CBR1 (by 17%) and GST (by 13%), while activities of these enzymes in the small intestine were unchanged. No changes in the relative amounts of these proteins were found. Taken together, the interactions of cranberry extract with simultaneously administered drugs seem not to be serious.

Effectiveness of an association of a cranberry dry extract, D-mannose, and the two microorganisms actobacillus plantarum LP01 and actobacillus paracasei LPC09 in women affected by cystitis: a pilot study.

Posted: April 1, 2015
Authors: Vicariotto F
Journal: J Clin Gastroenterol 48 Suppl 1:S96-101.

Abstract: BACKGROUND: Urinary tract infections (UTIs) are the most common bacterial infection in women. Most UTIs are acute uncomplicated cystitis caused by Escherichia coli (86%). This study was undertaken to assess the effectiveness of an association of a cranberry dry extract, D-mannose, a gelling complex composed of the exopolysaccharides produced by Streptococcus thermophilus ST10 (DSM 25246) and tara gum, as well as the 2 microorganisms Lactobacillus plantarum LP01 (LMG P-21021) and Lactobacillus paracasei LPC09 (DSM 24243) in women affected by acute uncomplicated cystitis.
MATERIALS AND METHODS: Thirty-three premenopausal, nonpregnant women diagnosed with acute uncomplicated cystitis were enrolled in a pilot prospective study and
completed the treatment protocol. Subjects were instructed to take 2 doses per day during the first month, and then to continue with 1 sachet per day until the sixtieth day. Nitrites and leukocyte esterase on urine dipstick testing were used
as indicators of cystitis, with analysis performed at enrollment, after 30 and 60 days, and after 1 month of follow-up. Typical UTI symptoms, namely dysuria, frequent voiding of small volumes, urinary urgency, suprapubic pain, and gross
hematuria were scored 0 to 3 and evaluated at each visit.
RESULTS: Positive results for the presence of nitrites and leukocyte esterase were found in 14 and 20 subjects after 30 days and in 9 and 14 women after 60 days, respectively (P<0.001). At the end of the follow-up period, positive
results for nitrites and leukocyte esterase were recorded in only 4 and 3 of 24 and 19 subjects (16.7%, P=0.103; 15.8%, P=0.325, respectively), with negative results after 60 days. Typical symptoms of cystitis, specifically dysuria, frequent voiding, urgency, and suprapubic pain were significantly improved as well. No significant differences were recorded in the incidence and severity of hematuria at any visit.
CONCLUSION: The long-term ability of an association of cranberry, D-mannose, an innovative gelling complex, and the 2 microorganisms tested to significantly improve the uncomfortable symptoms reported by women with acute cystitis has been suggested.

Efficient and cost-effective alternative treatment for recurrent urinary tract infections and interstitial cystitis in women: a two-case report.

Posted: April 1, 2015
Authors: Mansour A, Hariri E, Shelh S, Irani R, Mroueh M
Journal: Case Rep Med 2014:698758.

Abstract: Urinary tract infections (UTIs) are among the most common bacterial infections affecting women. UTIs are primarily caused by Escherichia coli, which increases the likelihood of a recurrent infection. We encountered two cases of recurrent
UTIs (rUTIs) with a positive E. coli culture, not improving with antibiotics due to the development of antibiotic resistance. An alternative therapeutic regimen based on parsley and garlic, L-arginine, probiotics, and cranberry tablets has been given. This regimen showed a significant health improvement and symptoms relief without recurrence for more than 12 months. In conclusion, the case supports the concept of using alternative medicine in treating rUTI and as a prophylaxis or in patients who had developed antibiotic resistance.

Evaluation of the effect of cranberry juice on symptoms associated with a urinary tract infection.

Posted: April 1, 2015
Authors: Bass-Ware A, Weed D, Johnson T, Spurlock A.
Journal: Urol Nurs 34(3):121-7

Abstract: The purpose of this research was to correlate daily consumption of cranberry juice and symptoms of a diagnosed UTI among 26 volunteer adult female patients

Evaluation of the in vitro/in vivo potential of five berries (bilberry, blueberry, cranberry, elderberry, and raspberry ketones) commonly used as herbal supplements to inhibit uridine diphospho-glucuronosyltransferase.

Posted: April 1, 2015
Authors: Choi EJ, Park JB, Yoon KD, Bae SK
Journal: Food Chem Toxicol 72:13-9.

Abstract: In this study, we evaluated inhibitory potentials of popularly-consumed berries (bilberry, blueberry, cranberry, elderberry, and raspberry ketones) as herbal supplements on UGT1A1, UGT1A4, UGT1A6, UGT1A9, and UGT2B7 in vitro. We also
investigated the potential herb-drug interaction via UGT1A1 inhibition by blueberry in vivo. We demonstrated that these berries had only weak inhibitory effects on the five UGTs. Bilberry and elderberry had no apparent inhibitions. Blueberry weakly inhibited UGT1A1 with an IC50 value of 62.4±4.40 &#956;g/mL and a Ki value of 53.1 &#956;g/mL. Blueberry also weakly inhibited UGT2B7 with an IC50 value of 147±11.1 &#956;g/mL. In addition, cranberry weakly inhibited UGT1A9 activity (IC50=458±49.7 &#956;g/mL) and raspberry ketones weakly inhibited UGT2B7 activity (IC50=248±28.2 &#956;g/mL). Among tested berries, blueberry showed the lowest IC50 value in the inhibition of UGT1A1 in vitro. However, the co-administration of blueberry had no effect on the pharmacokinetics of irinotecan and its active metabolite, SN-38, which was mainly eliminated via UGT1A1, in vivo. Our data suggests that these five berries are unlikely to cause clinically significant herb-drug interactions mediated via inhibition of UGT enzymes involved in drug metabolism. These findings should enable an understanding of herb-drug interactions for the safe use of popularly-consumed berries.

Gut-targeted immunonutrition boosting natural killer cell activity using Saccharomyces boulardii lysates in immuno-compromised healthy elderly subjects.

Posted: April 1, 2015
Authors: Naito Y, Marotta F, Kantah MK, Zerbinati N, Kushugulova A, Zhumadilov Z, Illuzzi N, Sapienza C, Takadanohara H, Kobayashi R, Catanzaro R.
Journal: Rejuvenation Res 17(2):184-7.

Abstract: The aim of this study was to assess the immunomodulatory effect of KC-1317 (a symbiotic mixture containing Saccharomyces boulardii lysate in a cranberry, colostrum-derived lactoferrin, fragaria, and lactose mixture) supplementation in immune-compromised but otherwise healthy elderly subjects. A liquid formulation of KC-1317 was administered in a randomized controlled trial (RCT) fashion to
healthy volunteers (65-79 years) previously selected for low natural killer (NK) cell activity, and this parameter was checked at the completion of the study. A significant improvement in NK cell activity of KC-1317 consumers was observed as
compared to placebo at the end of 2 months. Although preliminary, these beneficial immune-modulatory effects of KC-1317 in aged individuals might indicate its employment within a wider age-management strategy.

Inhibition of Pseudomonas aeruginosa PAO1 adhesion to and invasion of A549 lung epithelial cells by natural extracts.

Posted: April 1, 2015
Authors: Ahmed GF, Elkhatib WF, Noreddin AM
Journal: J Infect Public Health 7(5):436-44.

Abstract: Pseudomonas aeruginosa colonizes the lungs in cystic fibrosis (CF) and mechanically ventilated patients by binding to the cellular receptors on the surface of the lung epithelium. Studies have shown that blocking this interaction could be achieved with sub-minimum inhibitory concentrations of antibiotics such as ciprofloxacin. The development of bacterial resistance is a probable drawback of such an intervention. The use of natural extracts to interfere with bacterial adhesion and invasion has recently gained substantial attention and is
hypothesized to inhibit bacterial binding and consequently prevent or reduce pathogenicity. This study used an A549 lung epithelial cell infection model, and the results revealed that a combination of aqueous cranberry extract with ciprofloxacin could completely prevent the adhesion and invasion of P. aeruginosa PAO1 compared to the untreated control. All of the natural extracts (cranberry, dextran, and soybean extracts) and ciprofloxacin showed a significant reduction (P<0.0001) in P. aeruginosa PAO1 adhesion to and invasion of lung epithelial
cells relative to the control. The cranberry, dextran, and soybean extracts could substantially increase the anti-adhesion and anti-invasion effects of ciprofloxacin to the averages of 100% (P<0.0001), 80% (P<0.0001), and 60%
(P<0.0001), respectively. Those extracts might result in a lower rate of the development of bacterial resistance; they are relatively safe and inexpensive agents, and utilizing such extracts, alone or in combination with ciprofloxacin,
as potential anti-adhesion and anti-invasion remedies, could be valuable in preventing or reducing P. aeruginosa lung infections.

Microbial catabolism of procyanidins by human gut microbiota.

Posted: April 1, 2015
Authors: Ou K, Sarnoski P, Schneider KR, Song K, Khoo C, Gu L
Journal: Mol Nutr Food Res 58(11):2196-205.

Abstract: SCOPE: A major portion of ingested procyanidins is degraded by human microbiota in the colon into various phenolic compounds. These microbial metabolites are thought to contribute to the health benefits of procyanidins in vivo. The
objective of this study was to identify and quantify the microbial metabolites of procyanidins after anaerobic fermentation with human microbiota.
METHODS AND RESULTS: (-)-Epicatechin, (+)-catechin, procyanidin B2, procyanidin A2, partially purified apple and cranberry procyanidins were incubated with human
microbiota at a concentration equivalent to 0.5 mM epicatechin. GC-MS analysis showed that common metabolites of all six substrates were benzoic acid, 2-phenylacetic acid, 3-phenylpropionic acid, 2-(3'-hydroxyphenyl)acetic acid,
2-(4'-hydroxyphenyl)acetic acid, 3-(3'-hydroxyphenyl)propionic acid, and hydroxyphenylvaleric acid. 5-(3',4'-Dihydroxyphenyl)-&#947;-valerolactones and 5-(3'-hydroxyphenyl)-&#947;-valerolactones were identified as the microbial metabolites of epicatechin, catechin, procyanidin B2, and apple procyanidins but not from the procyanidin A2 or cranberry procyanidin ferments. 2-(3',4'-Dihydroxyphenyl)acetic acid was only found in the fermented broth of procyanidin B2, A2, apple, and cranberry procyanidins. The mass recoveries of microbial metabolites range from 20.0 to 56.9% for the six substrates after 24 h
of fermentation.
CONCLUSION: Procyanidins, both B-type and A-type can be degraded by human gut microbiota. The microbial metabolites may contribute to the bioactivities of procyanidins.

Non-toxic plant metabolites regulate Staphylococcus viability and biofilm formation: a natural therapeutic strategy useful in the treatment and prevention of skin infections.

Posted: April 1, 2015
Authors: Morán A, Gutiérrez S, Martínez-Blanco H, Ferrero MA, Monteagudo-Mera A, Rodríguez-Aparicio LB.
Journal: Biofouling 30(10):1175-82.

Abstract: In the present study, the efficacy of generally recognised as safe (GRAS) antimicrobial plant metabolites in regulating the growth of Staphylococcus aureus and S. epidermidis was investigated. Thymol, carvacrol and eugenol showed the
strongest antibacterial action against these microorganisms, at a subinhibitory concentration (SIC) of &#8804; 50 &#956;g ml(-1). Genistein, hydroquinone and resveratrol showed antimicrobial effects but with a wide concentration range (SIC = 50-1,000 &#956;g ml(-1)), while catechin, gallic acid, protocatechuic acid, p-hydroxybenzoic acid and cranberry extract were the most biologically compatible molecules (SIC &#8805; 1000 &#956;g ml(-1)). Genistein, protocatechuic acid, cranberry extract, p-hydroxybenzoic acid and resveratrol also showed anti-biofilm activity against S. aureus, but not against S. epidermidis in which, surprisingly, these metabolites stimulated biofilm formation (between 35% and 1,200%). Binary combinations of cranberry extract and resveratrol with genistein, protocatechuic or p-hydroxibenzoic acid enhanced the stimulatory effect on S. epidermidis biofilm formation and maintained or even increased S. aureus anti-biofilm

The effects of cranberries on preventing urinary tract infections.

Posted: April 1, 2015
Authors: Shin CN
Journal: Clin Nurs Res 23(1):54-79.

Abstract: Despite considerable controversy about their effects, cranberries in various forms have been used widely for several decades to prevent as well as treat urinary tract infections (UTIs). The purpose of this article is to present a review of research-based information regarding the ability of cranberries to prevent UTIs in adults at risk for UTIs. Current evidence suggests that cranberries decrease bacterial adherence to uroepithelial cells and thus decrease
the incidence of UTIs without adverse effects in most individuals. Thus clinicians may safely advise patients that cranberries are helpful in preventing UTIs. Cranberries may be a viable adjunct to antibiotics for patients with repeated UTIs.