This review addressed drug interactions precipitated by fruit juices other than grapefruit juice based on randomized controlled trials (RCTs). Literature was identified by searching PubMed, Cochrane Library, Scopus and Web of Science till December 30 2017. Among 46 finally included RCTs, six RCTs simply addressed pharmacodynamic interactions and 33 RCTs studied pharmacokinetic interactions, whereas seven RCTs investigated both pharmacokinetic and pharmacodynamic interactions. Twenty-two juice-drug combinations showed potential clinical relevance. The beneficial combinations included orange juice-ferrous fumarate, lemon juice-99mTc-tetrofosmin, pomegranate juice-intravenous iron during hemodialysis, cranberry juice-triple therapy medications for H. pylori, blueberry juice-etanercept, lime juice-antimalarials, and wheat grass juice-chemotherapy. The potential adverse interactions included decreased drug bioavailability (apple juice-fexofenadine, atenolol, aliskiren; orange juice-aliskiren, atenolol, celiprolol, montelukast, fluoroquinolones, alendronate; pomelo juice-sildenafil; grape juice-cyclosporine), increased bioavailability (Seville orange juice-felodipine, pomelo juice-cyclosporine, orange-aluminum containing antacids). Unlike furanocoumarin-rich grapefruit juice which could primarily precipitate drug interactions by strong inhibition of cytochrome P450 3A4 isoenzyme and P-glycoprotein and thus cause deadly outcomes due to co-ingestion with some medications, other fruit juices did not precipitate severely detrimental food-drug interaction despite of sporadic case reports. The extent of a juice-drug interaction may be associated with volume of drinking juice, fruit varieties, type of fruit, time between juice drinking and drug intake, genetic polymorphism in the enzymes or transporters and anthropometric variables. Pharmacists and health professionals should properly screen for and educate patients about potential adverse juice-drug interactions and help minimize their occurrence. Much attention should be paid to adolescents and the elderly who ingest medications with drinking fruit juices or consume fresh fruits during drug treatment. Meanwhile, more researches in this interesting issue should be conducted.

Objectives: Cranberries, high in polyphenols, have been associated with a favorable glycemic response in patients with type 2 diabetes and also are beneficial for oral health. Because type 2 diabetes mellitus and periodontal disease have a physiological relationship, this study aimed to evaluate the hypothesis that cranberry juice enriched with omega-3 will improve glycemic and lipid profiles and periodontal status in patients with diabetes with periodontal disease. Materials and Methods: In this randomized clinical trial, 41 patients with diabetes (age 35-67 years) with periodontal disease were recruited and randomly assigned to 4 groups: control (C; n=12), receiving omega-3 (I1; n=10, 1 g/twice daily), cranberry juice (I2; n=9, 200 ml, twice daily), and cranberry juice enriched with omega-3 (I3; n=10, 200 ml, containing 1 g omega-3) twice daily for 8 weeks. Nonsurgical periodontal therapy was provided for all patients during the study. Fasting blood glucose and glycated hemoglobin, lipid profile, probing depth, anthropometric indices, and 3-day 24-hour dietary recalls were measured pre- and postintervention. Results: Glycated hemoglobin was decreased significantly in I1 and I3 groups. Serum high-density lipoprotein cholesterol (HDL-C) levels increased significantly in the I3 group compared to baseline and compared to I1 and I2 groups. Probing depth was significantly reduced in all groups postintervention. Conclusion: Consumption of cranberry juice enriched with omega-3 can be beneficial as adjuvant therapy with nonsurgical periodontal therapy in decreasing glycated hemoglobin, increasing HDL-C, and improving periodontal status in patients with diabetes with periodontal disease.

Uropathogenic Escherichia coli (UPEC) is the main infectious agent of urinary tract infections (UTI) in humans, dogs and cats. Dietary consumption of cranberries is thought to be associated with prevention of UTI in humans based on decreased adhesion of UPEC to uroepithelial cells. The present study evaluated the impact of cranberry extract addition on the attachment of UPEC to canine Madin-Darby Canine Kidney and Crandell-Rees Feline Kidney uroepithelial cells. When the extract was present during bacterial growth or only during adhesion tests, a dose-dependent decrease of UPEC adhesion to all cell types was observed. Bacterial growth was weakly decreased only in the presence of the highest concentration of cranberry extract showing that the anti-adherence effect did not require a bacterial growth inhibitory effect. In conclusion, the addition of cranberry extract has preventive effects on the in vitro bacterial attachment to canine and feline uroepithelial cells in a dose dependent way.

Struvite or infection stones are one of the major clinical burdens among urinary tract infection, which occur due to the interaction between microbes and urine mineral components. Numerous urinary tract infection (UTI) causing microbes regulate through biofilm formation for survival from host defense, it is often found difficult in its eradication with simple anti-microbial agents and also the chance of recurrence and resistance development is significantly high. Cranberry consumption and maintenance of urinary tract health have been supported by clinical, epidemiological, and mechanistic studies. It predominantly contains proanthocyanidins that belong to the class of polyphenols with repeating catechin and epicatechin monomeric units. Numerous studies have correlated proanthocyanidin consumption and prevention of bacterial adhesion to uroepithelial cells. Quorum sensing (QS) is the prime mechanism that drives bacteria to coordinate biofilm development and virulence expression. Reports have shown that proanthocyanidins are effective in disrupting cell-cell communication by quenching signal molecules. Overall, this review assesses the merits of proanthocyanidins and its effective oppression on adherence, motility, QS, and biofilm formation of major UTI strains such as Escherichia coli, Pseudomonas aeruginosa, and Proteus mirabilis by comparing and evaluating results from many significant findings.

Uropathogenic Escherichia coli (UPEC), the most prevalent bacteria isolated in urinary tract infections (UTI), is now frequently resistant to antibiotics used to treat this pathology. The antibacterial properties of cranberry and propolis could reduce the frequency of UTIs and thus the use of antibiotics, helping in the fight against the emergence of antibiotic resistance. Transcriptomic profiles of a clinical UPEC strain exposed to cranberry proanthocyanidins alone (190micro g/mL), propolis alone (102.4micro g/mL) and a combination of both were determined. Cranberry alone, but more so cranberry+propolis combined, modified the expression of genes involved in different essential pathways: down-expression of genes involved in adhesion, motility, and biofilm formation, and up-regulation of genes involved in iron metabolism and stress response. Phenotypic assays confirmed the decrease of motility (swarming and swimming) and biofilm formation (early formation and formed biofilm). This study showed for the first time that propolis potentiated the effect of cranberry proanthocyanidins on adhesion, motility, biofilm formation, iron metabolism and stress response of UPEC. Cranberry+propolis treatment could represent an interesting new strategy to prevent recurrent UTI.

Study design: This study was a double-blind, placebo-controlled trial of a concentrated PACs compound (36mg/capsule), in veterans with SCI and neurogenic lower urinary tract dysfunction (NLUTD) requiring intermittent catheterization (IC) over a 15-day period. Objectives: The objective of this study was to evaluate the acute effects of concentrated proanthocyanidins (PACs) in the cranberry supplement ellura on bacteriuria, leukocyturia, and subjective urine quality in catheter-dependent veterans with SCI. Setting: Spinal cord injury center (outpatient clinic and inpatient unit). Methods: Participants with positive urine bacterial colonization (>=50K CFU/ml) were randomized to once daily concentrated PACs or identical placebo and followed with daily (in-patients) or twice weekly (out-patients) urine cultures with colony forming units per milliliter (cfu/ml) range (bacteriuria), microscopic urine white blood cells per high-powered field (wbc/hpf) quantification (leukocyturia), and surveys assessing urine clarity, odor, color, sediment, and overall satisfaction. A repeated measure analysis of variance was used to compare treatment vs. control and evaluate serial trends. Results: A total of 13 male participants (7 randomized to concentrated PACs, 6 to placebo) completed the trial. There was no significant decrease over the study period in colony forming units per milliliter (cfu/ml) or log(wbc/hpf) in the treatment vs. the control group. Patients receiving concentrated PACs rated the clarity, odor, color, sediment, and overall satisfaction of their urine as insignificantly improved compared to placebo. Conclusions: Acutely, there was no reduction of bacteriuria and pyuria or improvement in subjective urine quality for SCI patients treated with daily concentrated PACs.

Blueberry and cranberry are fruits with high polyphenol content, particularly anthocyanins. As cyanidin derivatives have been identified as one of the most representative polyphenols in berry juices, cyanidin has been designated for a better comparison and understanding of the potential neuroprotection of juices obtained from two Vaccinium species. Neuroblastoma SH-SY5Y cells were previously treated with different concentrations of lyophilized blueberry juice, cranberry juice or cyanidin for 24h and oxidative stress was then generated with hydrogen peroxide (100muM) for 30min. Cytoprotective properties of cranberry juice, blueberry juice or cyanidin were evaluated using different methodologies such as mitochondrial activity (MTT), TBARS and ROS production, antioxidant enzymes (CAT, SOD) and antioxidant properties (ORAC, FRAP). Results indicated that blueberry and cranberry juices as well as cyanidin increased mitochondrial activity and reduced intracellular ROS production and lipid peroxidation induced by hydrogen peroxide. Furthermore, these berry juices and cyanidin upregulated the activity of the antioxidant enzymes catalase and superoxide dismutase. Finally, in vitro antioxidant capacities were confirmed by ORAC and FRAP assays demonstrating the potential of cyanidin and cyanidin-containing products for pharmaceutical or nutritional applications to prevent oxidative stress in neuronal cells.

Background/Aims: Clinical trials of older adults are increasingly common, but risks of serious adverse events (SAE) may vary. We describe the incidence of SAE in two randomized trials, one community-based and one nursing home-based. Methods: We performed a secondary data analysis from two randomized clinical trials at one academic health center and 21 nursing homes involving 200 sedentary community dwellers aged 70-89 years and 185 female nursing home residents aged 65 years or older. Interventions included structured physical activity to reduce mobility disability in the Lifestyle Interventions and Independence for Elders (LIFE) study and oral cranberry capsules to reduce bacteriuria plus pyuria in nursing home residents (CRANNY) trial. We measured SAE incidence per 100 person-years and incidence of protocol-related unanticipated SAE per 100 person-years in LIFE and CRANNY trials. Results: Mean age and proportion of patients with dementia in LIFE and CRANNY trials were 79.3 years and 86.4 years and 0% and 78%, respectively. There were 179 total SAE in LIFE including 8 (4%) deaths, and 116 total SAE in CRANNY including 33 (28%) deaths. SAE incidence was 33.7 (95% CI 27.2, 41.8) events per 100 person-years in LIFE and 69.4 (95% CI 49.1, 98.1) events per 100 person-years in CRANNY. No protocol-related unanticipated SAE occurred in either trial. Conclusions: The frequency and severity of SAE vary in older adults. While SAE are common in nursing home residents, protocol-related, unanticipated SAE are rare in nursing home residents and community dwellers. This finding can inform trial monitoring protocols.

American cranberry (Vaccinium macrocarpon) is native to Eastern North America. Recent studies have suggested that the A-type proanthocyanidins (PACs) in cranberries are effective in preventing urinary tract infection. To meet the growing interest in the cranberry market, an accurate, reliable, and simple method to determine PAC concentration is needed. In this study, a modified method using 4-dimethylaminocinnamaldehyde to quantify total PACs in cranberry products was validated. Cranberry juice extract powder, cranberry capsules containing juice extract, and cranberry juice concentrate were used as the samples in this study. With the modified method, the calibration curves for proanthocyanidin A2 had correlation coefficients (r2) of >0.99. The recoveries of two different concentrations after spiking were 97.1 and 99.1%, and the RSDs for repeatability and reproducibility were <2.7 and <1.6%, respectively.

BACKGROUND: Urinary tract infections (UTIs) are amongst the most common bacterial infections affecting women. Although antibiotics are the treatment of choice for UTI, cranberry derived products have been used for many years to prevent UTIs, with limited evidence as to their efficacy. Our objective is to assess the efficacy of a cranberry extract capsule standardized in A-type linkage proanthocyanidins (PACs) for the prevention of recurrent urinary tract infection. METHODS: We will perform a 1:1 randomized, controlled, double blind clinical trial in women aged 18 years or more who present >=2 UTIs in 6 months or>=3 UTIs in 12 months. One hundred and forty-eight women will be recruited and randomized in two groups to either receive an optimal dose of cranberry extract quantified and standardized in PACs (2x18.5 mg PACs per day) or a control dose (2x1 mg PACs per day). The primary outcome for the trial is the mean number of new symptomatic UTIs in women during a 6-month intervention period. Secondary outcomes are: (1) To evaluate the mean number of new symptomatic UTIs with pyuria as demonstrated by a positive leucocyte esterase test; (2) To detect the mean number of new symptomatic culture-confirmed UTIs; (3) To quantify urinary PACs metabolites in women who take a daily dose of 37 mg PACs per day compared to women who take a daily dose of 2 mg per day for 6 months; (4) To characterize women who present recurrent UTI based on known risk factors for recurrent UTI; (5) To describe the side effects of daily intake of cranberry extract containing 37 mg PACs compared to 2 mg PACs. This report provides comprehensive methodological data for this randomized controlled trial. DISCUSSION: The results of this trial will inform urologists, gynaecologists, family physicians and other healthcare professionals caring for healthy women with recurrent UTI, as to the benefits of daily use of an optimal dose of cranberry extract for the prevention of recurrent UTI.