A growing body of evidence suggests that nutraceuticals with prolongevity properties may delay the onset of Alzheimer's disease (AD). We recently demonstrated that a proanthocyanidins-standardized cranberry extract has properties that prolong life span and promote innate immunity in Caenorhabditis elegans. In this article, we report that supplementation of this cranberry extract delayed A beta toxicity-triggered body paralysis in the C. elegans AD model. Genetic analyses indicated that the cranberry-mediated A beta toxicity alleviation required heat shock transcription factor (HSF)-1 rather than DAF-16 and SKN-1. Moreover, cranberry supplementation increased the transactivity of HSF-1 in an IIS-dependent manner. Further studies found that the cranberry extract relies on HSF-1 to significantly enhance the solubility of proteins in aged worms, implying an improved proteostasis in AD worms. Considering that HSF-1 plays a pivotal role in maintaining proteostasis, our results suggest that cranberry maintains the function of proteostasis through HSF-1, thereby protecting C. elegans against A beta toxicity. Together, our findings elucidated the mechanism whereby cranberry attenuated A beta toxicity in C. elegans and stressed the significance of proteostasis in the prevention of age-related diseases from a practical point of view.

Background and Objectives. Recently, we described an inverse association between cranberry supplementation and serum prostate specific antigen (PSA) in patients with negative biopsy for prostate cancer (PCa) and chronic nonbacterial prostatitis. This double blind placebo controlled study evaluates the effects of cranberry consumption on PSA values and other markers in men with PCa before radical prostatectomy. Methods: Prior to surgery, 64 patients with prostate cancer were randomized to a cranberry or placebo group. The cranberry group (n=32) received a mean 30 days of 1500 mg cranberry fruit powder. The control group (n=32) took a similar amount of placebo. Selected blood/urine markers as well as free and total phenolics in urine were measured at baseline and on the day of surgery in both groups. Prostate tissue markers were evaluated after surgery. Results: The serum PSA significantly decreased by 22.5% in the cranberry arm (n=31, P<0.05). A trend to down-regulation of urinary beta-microseminoprotein (MSMB) and serum gamma-glutamyltranspeptidase, as well as upregulation of IGF-1 was found after cranberry supplementation. There were no changes in prostate tissue markers or, composition and concentration of phenolics in urine. Conclusions: Daily consumption of a powdered cranberry fruit lowered serum PSA in patients with prostate cancer. The whole fruit contains constituents that may regulate the expression of androgen-responsive genes.

Background: Due to the higher susceptibility of metabolic syndrome (MS)-afflicted patients to different metabolic abnormalities, treatment programs are vital parts of MS management. One of the possible adjunctive therapies is taking cranberry supplements as important sources of polyphenols that bear antioxidative and health-promoting properties.Objectives: The aim of this study was to evaluate the effect of cranberry extract on some components of metabolic syndrome.Patients and Methods: In a randomized, double-blind placebo-controlled clinical trial, 48 obese and overweight females diagnosed with MS were assigned into two groups to receive cranberry supplement or placebo for an eight-week period. Serum glucose, lipoproteins, inflammatory markers and blood pressure were evaluated at the baseline and at the end of the treatment phase.Results: Cranberry supplements had no effect on any of the variables including glucose, insulin, malondialdehyde (MDA), high-sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), and blood pressure, except for high-density lipoprotein cholesterol (HDL-c), which significantly increased (P < 0.05) at the eighth-week period compared with the placebo samples.Conclusions: The results of the present study revealed that cranberry supplement might only ameliorate low HDL-c as a component of metabolic syndrome, and not the other risk factors of MS.

Anthocyanins are a group of widespread natural phenolic compounds in vegetables and fruits. The anthocyanins have a wide range of applications due to the antioxidant, anticancer and anti-inflammatory properties. In this study, anthocyanins (delphinidin-3-o-glucoside, cyanidin-3-o-glucoside, pelargonidin-3-o-glucoside and malvidin-3-o-glucoside) in cherry and cranberry were determined using high-performance liquid chromatography–electrospray ionization–mass spectrometry (HPLC–ESI–MS). The anthocyanins were separated using gradient elution and a reserved-phase analytical column before identification by high-performance liquid chromatography–electrospray ionization–mass spectrometry. A high-performance liquid chromatography–electrospray ionization–mass spectrometry method was optimized for the determination of anthocyanins in cherry and cranberry. Furthermore, in this study, we investigated extraction conditions of fruit samples as well as determination of optimum HPLC–ESI–MS conditions. This study is novel in terms of simultaneously examining both optimization of HPLC parameters and extraction conditions. Obtained optimum conditions were used for the determination as the quantitative and qualitative analysis of anthocyanins in cherry and cranberry. The content of anthocyanins on the basis of wet weight in cherry and cranberry samples was determined for delphinidin-3-o-glucoside

Bacteriuria plus pyuria is highly prevalent among older women living in nursing homes.Cranberry capsules are an understudied, nonantimicrobial prevention strategy used in this population. Objective:To test the effect of 2 oral cranberry capsules once a day on presence of bacteriuria plus pyuria among women residing in nursing homes.Design, Setting, and Participants:Double-blind, randomized, placebo-controlled efficacy trial with stratification by nursing home and involving 185 English-speaking women aged 65 years or older, with or without bacteriuria plus pyuria at baseline, residing in 21 nursing homes located within 50 miles (80 km) of New Haven, Connecticut (August 24, 2012-October 26, 2015).Interventions:Two oral cranberry capsules, each capsule containing 36 mg of the active ingredient proanthocyanidin (ie, 72 mg total, equivalent to 20 ounces of cranberry juice) vs placebo administered once a day in 92 treatment and 93 control group participants.Main Outcomes and Measures:Presence of bacteriuria (ie, at least 105 colony-forming units [CFUs] per milliliter of 1 or 2 microorganisms in urine culture) plus pyuria (ie, any number of white blood cells on urinalysis) assessed every 2 months over the 1-year study surveillance; any positive finding was considered to meet the primary outcome. Secondary outcomes were symptomatic urinary tract infection (UTI), all-cause death, all-cause hospitalization, all multidrug antibiotic-resistant organisms, antibiotics administered for suspected UTI, and total antimicrobial administration.Results:Of the 185 randomized study participants (mean age, 86.4 years [SD, 8.2], 90.3% white, 31.4% with bacteriuria plus pyuria at baseline), 147 completed the study. Overall adherence was 80.1%. Unadjusted results showed the presence of bacteriuria plus pyuria in 25.5% (95% CI, 18.6%-33.9%) of the treatment group and in 29.5% (95% CI, 22.2%-37.9%) of the control group. The adjusted generalized estimating equations model that accounted for missing data and covariates showed no significant difference in the presence of bacteriuria plus pyuria between the treatment group vs the control group (29.1% vs 29.0%; OR, 1.01; 95% CI, 0.61-1.66; P = .98). There were no significant differences in number of symptomatic UTIs (10 episodes in the treatment group vs 12 in the control group), rates of death (17 vs 16 deaths; 20.4 vs 19.1 deaths/100 person-years; rate ratio [RR], 1.07; 95% CI, 0.54-2.12), hospitalization (33 vs 50 admissions; 39.7 vs 59.6 hospitalizations/100 person-years; RR, 0.67; 95% CI, 0.32-1.40), bacteriuria associated with multidrug-resistant gram-negative bacilli (9 vs 24 episodes; 10.8 vs 28.6 episodes/100 person-years; RR, 0.38; 95% CI, 0.10-1.46), antibiotics administered for suspected UTIs (692 vs 909 antibiotic days; 8.3 vs 10.8 antibiotic days/person-year; RR, 0.77; 95% CI, 0.44-1.33), or total antimicrobial utilization (1415 vs 1883 antimicrobial days; 17.0 vs 22.4 antimicrobial days/person-year; RR, 0.76; 95% CI, 0.46-1.25).Conclusions and Relevance:Among older women residing in nursing homes, administration of cranberry capsules vs placebo resulted in no significant difference in presence of bacteriuria plus pyuria over 1 year.Trial Registration:clinicaltrials.gov Identifier: NCT01691430.

Please see this link for the Cranberry Institute's official statement regarding this research: http://www.cranberryinstitute.org/HCP/cranutiresponse.html

In the present study, anti-proliferative activities of cranberry derived flavonoids and some of their in vivo metabolites were evaluated using a panel of human bladder tumor cell lines (RT4, SCABER, and SW-780) and non-tumorigenic immortalized human uroepithelial cells (SV-HUC). Among the compounds tested, quercetin 3-O-glucoside, isorhamnetin (3'-O-methylquercetin), myricetin and quercetin showed strong concentration-dependent cell growth inhibitory activities in bladder cancer cells with IC50 values in a range of 8-92 micro M. Furthermore, isorhamnetin and myricetin had very low inhibitory activity against SV-HUC even at very high concentrations (>200 micro M) compared to bladder cancer cells, indicating that their cytotoxicity is selective for cancer cells. To determine whether the differential cell growth inhibitory effects of isomeric flavonoids quercetin 3-O-glucoside (active) and hyperoside (quercetin 3-O-galactoside) (inactive) are related to their metabolism by the cancer cells, SW-780 cells were incubated with these compounds and their metabolism was examined by LC-MS/MS. Compared to quercetin 3-O-glucoside, hyperoside undergoes relatively less metabolic biotransformation (methylation, glucuronidation and quinone formation). These data suggest that isorhamnetin and quercetin 3-O-glucoside may be the active forms of quercetin in prevention of bladder cancer in vivo and emphasize the importance of metabolism for the prevention of bladder cancer by diets rich in cranberries.

The intestinal absorption of bacterial lipopolysaccharide (LPS) and dietary fat has been implicated in the development of metabolic endotoxemia. This study first compared the ability of polyphenol extracts from grape, cranberry, avocado and apple to interfere with pancreatic lipase and LPS in vitro. The grape extract displayed a higher inhibitory activity of lipase (IC50=8.6+or-1.1 mg/ml) and LPS binding (IC50=90+or-1.1 micro g/ml). Then, a study was carried out in 12 normal weight and 17 overweight/obese subjects to determine the effect of this extract on the postprandial changes in plasma triacylglycerols, LPS and IL-6. The presence of small intestine bacterial overgrowth (SIBO), in which higher levels of bacteria and eventually LPS are present in the upper intestine, i.e. where dietary fat absorption occurs, was also evaluated. Compared with placebo, the grape extract did not affect postprandial triacylglycerolemia but decreased plasma LPS, without affecting the IL-6-associated inflammatory response. SIBO did not affect these variables.

Drinking of cranberry fruit juice and application of commercial preparations containing the cranberry extracts are recommended in the prevention and treatment of urinary tract infections (UTIs), especially in women with recurrent UTIs. Many studies focus on the activity of cranberries against uropathogenic Escherichia coli (E. coli) strains. However, the knowledge of the cranberry effect on Gram-positive Enterococcus faecalis (E. faecalis) is limited. Therefore, the aim of our study was to establish the activity of commercial concentrated cranberry extract on the growth, virulence factors and biofilm formation of E. faecalis strains isolated from urine. Minimal inhibitory concentrations (MICs) of cranberry extract were determined by the broth microdilution method. Disc diffusion method was used to determine antimicrobial susceptibility. The impact of cranberry extract on bacterial survival, hydrophobicity, synthesis of lipase, lecithinase, DNase, hemolysin, gelatinase and biofilm mass was determined. Results show that cranberry extract inhibits the growth, enzymatic activities of bacteria and limits biofilm formation. The antibacterial activities of the studied cranberry extract confirm that it could be successfully used in prevention of UTIs caused by E. faecalis.

OBJECTIVE: Recently, cranberry extracts have been tested as a nutritional supplementation in the prevention of lower urinary tract symptoms (LUTS) as well as recurrent urinary tract infections (UTIs) in subjects at risk, with mixed results. However, evidence of efficacy should be considered only for well-characterized and standardized products in a more selected study population. Moreover, the efficacy of these interventions in elderly must be further investigated. The aim of this pilot, registry study was to evaluate the prophylactic effects of an oral supplementation containing a highly concentrated and standardized cranberry extract reproducing the natural total profile of cranberry fruits, in elderly men with benign prostatic hyperplasia (BPH), suffering from recurrent UTIs, over a 2-months follow-up.PATIENTS AND METHODS: 43 men (age > 65 years) enrolled in this study freely decided to receive either a standard management (SM) only (n = 21) or SM associated with an oral supplementation (n = 23). Supplementation consisted in a daily administration of one capsule containing cranberry extract (Anthocran®) for 60 consecutive days. The clinical effectiveness in the prevention of UTIs was determined by the number of UTIs in the two months before the inclusion in the registry and during the supplementation period, and the number of symptom-free subjects during the registry period. Safety considerations were also performed.RESULTS: In the supplemented group, the mean number of UTI episodes reported during the registry (0.8 ± 0.5) significantly decreased compared with inclusion time (3.2 ± 1.3), p-value = 0.0001. No significant changes were observed in control, SM-only group. Importantly, the cranberry oral supplementation was superior over SM at reducing the mean number of UTIs (p-value = 0.0062).CONCLUSIONS: These results suggest that cranberry supplementation could be an effective and safe approach, within an SM program, for the prevention of recurrent UTIs in elderly men suffering from BPH avoiding some antibiotic treatments.

Ultrahigh pressure liquid chromatography-atmospheric pressure photoionization-tandem mass spectrometry (UHPLC-APPI-MS/MS) was applied to the analysis and authentication of fruit-based products and pharmaceutical preparations. Two sub-2 micro m C18 reversed-phase columns, Syncronis (100x2.1 mm, 1.7 micro m) and Hypersil Gold (50x2.1 mm, 1.9 micro m), were proposed under gradient elution with 0.1% formic acid aqueous solution and methanol mobile phases for the determination of 29 polyphenols, allowing us to obtain polyphenolic profiles in less than 13.5 and 23.5 min, respectively. Several atmospheric pressure ionization (API) sources (H-ESI, APCI, and APPI) were compared. For dopant-assisted APPI, four organic solvents, toluene, acetone, chlorobenzene and anisole, were evaluated as dopants. Both H-ESI and acetone-assisted APPI were selected as the best ionization sources for the analysis of targeted polyphenols. Acceptable sensitivity (LOD values down to 0.5 micro g kg-1 in the best of cases), linearity (r2 higher than 0.995) and good precision (RSD values lower than 15.1%) and trueness (relative errors lower than 10.2%) were obtained using both UHPLC-API-MS/MS methods. A simple extraction procedure, consisting of sample sonication with acetone/water/hydrochloric acid (70:29.9:0.1 v/v/v) and centrifugation, was used. The proposed UHPLC-ESI-MS/MS and UHPLC-APPI-MS/MS methods with both C18 reversed-phase columns were then applied to the analysis of 32 grape-based and cranberry-based natural products and pharmaceutical preparations. Polyphenolic profile data were then analyzed by principal component analysis (PCA) to extract information on the most significant data contributing to the classification of natural extracts according to the type of fruit.