Consumption of cranberry fruits or juice rich in polyphenols is associated with a wide range of potential health benefits. We and others have previously showed that cranberry juice concentrate and its phytochemicals, flavonols, anthocyanins and A-type proanthocyandins, may have potential to be chemopreventive agents. Although a number of cranberry constituents have been implicated in cancer prevention, our understanding about which metabolites are bio-available to reach target sites and thereby elicit cancer chemopreventive properties is still lacking. However, poor plasma bioavailability of cranberry constituents may be overcome by their potential interactions with gut microbiota by providing cancer prevention through induction of compositional and functional modifications of gut microbiota. Well-designed clinical trials evaluating metabolic and gut microbiome changes associated with cranberry consumption would provide useful information about the cancer patient’s response to dietary intervention with cranberry constituents.

Studies have shown that cranberry and its components may exert anticancer properties. The present study aims to critically summarise the existing experimental studies evaluating the potential effects of cranberry on cancer prevention and treatment. PubMed database was searched to identify rele-vant studies. Current in vitro studies have indicated that cranberry and/or its components may act as chemopreventive agents, diminishing the risk for cancer by inhibiting cells oxidation and inflammatory-related processes, while they may also exert chemotherapeutic effects by inhibiting cell proliferation and angiogenesis, inducing cell apoptosis and attenuating the ability of tumour cells to invade and metastasis. Limited in vivo studies have further documented potential anticancer activity. Cranberry could be considered as a conglomeration of potential effective anticancer drug-like compounds.

The opportunistic pathogen Escherichia coli, a common member of the human gut microbiota belonging to the Enterobacteriaceae family, is the causative agent of the majority of urinary tract infections (UTIs). The gut microbiota serves as a reservoir for uropathogenic E. coli where they are shed in feces, colonize the periurethral area, and infect the urinary tract. Currently, front line treatment for UTIs consists of oral antibiotics, but the rise of antibiotic resistance is leading to higher rates of recurrence, and antibiotics cause collateral damage to other members of the gut microbiota. It is commonly believed that incorporation of the American cranberry, Vaccinium macrocarpon, into the diet is useful for reducing recurrence of UTIs. We hypothesized such a benefit might be explained by a prebiotic or antimicrobial effect on the gut microbiota. As such, we tested cranberry extracts and whole cranberry powder on a human gut microbiome-derived community in a gut simulator and found that cranberry components broadly modulate the microbiota by reducing the abundance of Enterobacteriaceae and increasing the abundance of Bacteroidaceae. To identify the specific compounds responsible for this, we tested a panel of compounds isolated from cranberries for activity against E. coli, and found that salicylate exhibited antimicrobial activity against both laboratory E. coli and human UTI E. coli isolates. In a gut simulator, salicylate reduced levels of Enterobacteriaceae and elevated Bacteroidaceae in a dose dependent manner.

Aggregatibacter actinomycetemcomitans is a Gram-negative bacterium that has been strongly associated with localized aggressive periodontitis. The capacity of A. actinomycetemcomitans to produce a leukotoxin (LtxA) that activates pyroptosis in macrophages and induces the release of endogenous danger signals is thought to play a key role in the disease process. The aim of the present study was to investigate the effects of cranberry proanthocyanidins (PACs) on gene expression and cytotoxic activities of LtxA. We showed that cranberry PACs dose-dependently attenuate the expression of genes making up the leukotoxin operon, including ltxB and ltxC, in the two strains of A. actinomycetemcomitans tested. Cranberry PACs (≥62.5 µg/mL) protected macrophages against the cytotoxic effect of purified LtxA. Moreover, cranberry PACs reduced caspase-1 activation in LtxA-treated macrophages and consequently decreased the release of both IL-1β and IL-18, which are known as damage-associated molecular patterns (DAMPs) and contribute to the progression of periodontitis by increasing cell migration and osteoclastogenesis. In addition, cranberry PACs reduced the expression of genes encoding the P2X7 receptor and NALP3 (NACHT, LRR and PYD domains-containing protein 3), which play key roles in pore formation and cell death. Lastly, cranberry PACs blocked the binding of LtxA to macrophages and consequently reduced the LtxA-mediated cytotoxicity. In summary, the present study showed that cranberry PACs reduced LtxA gene expression in A. actinomycetemcomitans and neutralized the cytolytic and pro-inflammatory responses of human macrophages treated with LtxA. Given these properties, cranberry PACs may represent promising molecules for prevention and treatment of the aggressive form of periodontitis caused by A. actinomycetemcomitans.

Objective: We assessed the effect on lower urinary tract symptoms (LUTS) of a supplement containing cranberry, D-mannose and anti-inflammatory molecules in postmenopausal women undergoing surgery for cystocele.Study design: Forty postmenopausal women were randomized 1:1 to an active group receiving the nutritional supplement twice a day for 2 weeks starting from surgery, or to a control group receiving surgery only. Primary outcomes were the effectiveness in the postoperative LUTS and urinary tract infections (UTI). LUTS were investigated by a validated questionnaire (ICIQ-FLUTS) at baseline and at week 4. Secondary outcomes were the safety and tolerability of the supplement and other perioperative outcomes.Results: No significant differences were found in perioperative outcomes and in incidence of UTI. After surgery, women treated with the supplement experienced significantly better scores on the filling domain of the questionnaire. A non-significant decrease in voiding scores was also found. No adverse events were detected.Conclusion: The use of an oral supplement containing cranberry, D-mannose and anti-inflammatory molecules decreases the perception of LUTS in postmenopausal women after anterior colporraphy. Our data suggest that perioperative use of nutritional supplements may be useful in the management of postoperative LUTS.

Dietary berries are a rich source of several nutrients and phytochemicals and in recent years, accumulating evidence suggests they can reduce risks of several chronic diseases, including type 2 diabetes (T2D). The objective of this review is to summarize and discuss the role of dietary berries (taken as fresh, frozen, or other processed forms) on insulin resistance and biomarkers of T2D in human feeding studies. Reported feeding trials involve different berries taken in different forms, and consequently differences in nutritional or polyphenol composition must be considered in their interpretation. Commonly consumed berries, especially cranberries, blueberries, raspberries and strawberries, ameliorate postprandial hyperglycemia and hyperinsulinemia in overweight or obese adults with insulin resistance, and in adults with the metabolic syndrome (MetS). In non-acute long-term studies, these berries either alone, or in combination with other functional foods or dietary interventions, can improve glycemic and lipid profiles, blood pressure and surrogate markers of atherosclerosis. Studies specifically in people with T2D are few, and more knowledge is needed. Nevertheless, existing evidence, although sparse, suggests that berries have an emerging role in dietary strategies for the prevention of diabetes and its complications in adults. Despite the beneficial effects of berries on diabetes prevention and management, they must be consumed as part of a healthy and balanced diet.

Cranberry volatiles have received little attention for health-promoting properties. In this study, we compared the inhibitory effects of cranberry polyphenol and volatile extracts and volatile standards on nitric oxide (NO) production in lipopolysaccharide (LPS) activated RAW 264.7 macrophages. Polyphenols were analyzed by HPLC/HPLC-MS and volatiles were analyzed by GC/GC-MS. The inhibition of NO production of the fresh cranberry polyphenol and volatile extracts and alpha -terpineol, linalool, linalool oxide, and eucalyptol standards at 2, 4, and 8-fold dilutions of their original concentrations in fresh cranberries was evaluated by treating these extracts/standards for 1 h before or after LPS application for 24 h. After inducing inflammation with LPS, the polyphenol treatments (317.8 and 635.7 micro g g-1) and 1.8 micro g g-1 volatile treatment lowered NO levels 46-62% compared to the positive control (P<0.05). When the cells were treated with polyphenol and volatile extracts before inducing inflammation, the 635.7 micro g g-1 and 317.8 micro g g-1 polyphenol treatments and 1.8 micro g g-1 and 0.9 micro g g-1 volatile treatments lowered NO levels (13-52%) compared to the positive control (P<0.05). Polyphenol and volatile extracts from cranberry were effective in reducing NO production whether applied before or after the application of LPS. alpha -Terpineol at a concentration found in fresh cranberries (1.16 micro g mL-1) was also found to be effective in reducing NO production whether cells were treated before or after application of LPS. Future studies are needed to reveal the mechanisms by which volatile compounds, especially alpha -terpineol act to mitigate inflammation and to determine the bioavailability of terpenes.

This review summarizes the mechanistic and clinical research on the use of cranberry as an alternative management strategy for H. pylori bacteria in populations at high risk for infection-induced peptic ulcers and gastric cancer. The multiple mechanisms of action of cranberry polyphenols and how they may be applied in relation to what is known about the pathogenicity of H. pylori offers opportunity for utilizing this fruit to potentially help lower the incidence of ulcers and concomitant gastric cancer.

Objectives: To assess efficacy and safety of Bio-Kult Pro-Cyan (BKPro-Cyan), a product containing two strains of Lactobacilli plus cranberry extract, for preventing recurrent UTIs in pre-menopausal adult women. Methods: This was a randomized, double-blind, placebo-controlled pilot study. Subjects received BKPro-Cyan or placebo twice-daily for 26 weeks. The primary endpoint was the proportion of subjects with recurrent UTI at the end of the study. Results: 115 subjects were screened; 90 were enrolled; 81 completed the study. After 26 weeks, a significantly lower number of women experienced recurrent UTIs with BKPro-Cyan compared to placebo (9.1 vs 33.3%; P=0.0053). BKPro-Cyan produced statistically significant improvements compared to placebo for multiple secondary endpoints, including: greater number of subjects who experienced no UTIs (90 vs 67%; P<0.05); longer time to first UTI (174 vs 90 days; P=0.001); shorter duration of active UTI (5 vs 12 days; P=0.009); Fewer subjects requiring antibiotics (3 vs 11; P<0.05); and shorter median duration of antibiotic treatment (4 vs 7 days; P=0.09). Conclusions: BKPro-Cyan was safe and effective for preventing recurrent UTI in pre-menopausal adult women. These findings support the need for further well-designed trials to clarify the benefits that may be achieved.

Blood lipids are an important biomarker of cardiovascular health and disease. Among the lipid biomarkers that have been widely used to monitor and predict cardiovascular diseases (CVD), elevated LDL and low HDL cholesterol (C), as well as elevated triglyceride-rich lipoproteins, deserve special attention in their predictive abilities, and thus have been the targets of several therapeutic and dietary approaches to improving lipid profiles. Among natural foods and nutraceuticals, dietary berries are a rich source of nutrients, fiber, and various types of phytochemicals. Berries as whole fruits, juices, and purified extracts have been shown to lower total and LDL-C, and increase HDL-C in clinical studies in participants with elevated blood lipids, type 2 diabetes or metabolic syndrome. This short review aimed to further discuss the mechanisms and magnitude of the lipid-lowering effects of dietary berries, with emphasis on reported clinical studies. Based on the emerging evidence, colorful berry fruits may thus be included in a healthy diet for the prevention and management of CVD.