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Chemopreventive potential of cranberries on azoxymethane induced aberrant crypt foci in Fisher 344 male rats

Posted: December 17, 2010
Authors: Sunkara R, Verghese M, Panala V, Field R, Boateng J, Shackelford L. A. and Walker, L. T.
Journal: Int J Canc Res 4 (2):52-60

Abstract: In this study, the chemopreventive potential of Cranberry was analyzed in reducing the Aberrant Crypt Foci (ACF) induced by Azoxymethane (AOM) in Fisher 344 male rats. After 1 week period of acclimatization, rats were divided into five different groups. Cranberry meal was mixed in an AIN 93G based diet at 5 and 10% and juice was provided at 2.5 and 5%. Daily feed intake and weekly body weights were recorded. At 17 week of age, rats were killed and samples were collected. Number of ACF and number of crypts/foci were enumerated in the colon. There were no significant differences in feed intake, weight gain, cecal weight and cecal pH among all groups. Total ACF incidence (119) was significantly (p<0.05) higher in control group than in treatment groups. Reduction in total ACF induction was higher in rats fed 10% Cranberry (65.75%) compared to control. A two to six fold increase in selected hepatic enzymes activities (units/mg enzyme) were seen in rats fed 5 and 10% treatment diets compared to control. Results of this study showed that administration of Cranberry meal and juice resulted in significant (p<0.05) reductions in the incidence of ACF in azoxymethane induced preneoplastic lesions.

Cranberry synergies for dietary management of Helicobacter pylori infections

Posted: December 17, 2010
Authors: Vattem DA, Lin YT, Ghaedian R, Shetty K
Journal: Process Biochem 40(5):1583-1592

Abstract: Cranberry and its products are important components of the cranberry processing industry and have historically been associated with positive health benefits such as preventing urinary tract infections. These health benefits are associated with phenolic phytochemicals in the juice which are now known to have potential for inhibition of development and progression of cancer and cardiovascular diseases. Helicobacter pylori is an important human pathogen linked to peptic ulcer and now to cardiovascular diseases. Control of this pathogen using synthetic antimicrobials such as currently approved antibiotics has limitations due to potential development of resistance and low compliance. We believe a profile of antimicrobials compared to a single compound could be potentially more effective in managing H. pylori infections. We have investigated the effect of cranberry, blueberry and grape seed extracts on inhibiting H. pylori have been investigated. The ability of blueberry, grape seed and oregano extract on enhancing the antioxidant and anti-H. pylori activity of cranberry powder in a mixture was also investigated. The anti-H. pylori activity of the cranberry fruit extracts and their synergies correlated with antioxidant activity and the presence of biphenyls as well as polyphenolic phytochemicals. The anti-H. pylori activity of cranberry juice extract was significantly improved by its synergistic blending with blueberry, grape seed and oregano extract. The lower efficacy of purified phenolics in inhibiting H. pylori compared with fruit powder at similar dosage levels suggests a synergistic mode of functionality of these individual phenolics in whole food background. Consumption of blends of fruit juices with other fruit as well as herb extracts can impart unique functional attributes and could be an effective strategy in developing diet-based management of H. pylori infections as well as other oxidation linked diseases.

Inhibitory effects of cranberry polyphenols on formation and acidogenicity of Streptococcus mutans biofilms

Posted: December 17, 2010
Authors: Duarte S, Gregoire S, Singh AP, Vorsa N, Schaich K, Bowen WH, Koo H
Journal: FEMS Microbiol Lett 257(1):50-56

Abstract: Cranberry fruit is a rich source of polyphenols, and has shown biological activities against Streptococcus mutans. In the present study, we examined the influence of extracts of flavonols (FLAV), anthocyanins (A) and proanthocyanidins (PAC) from cranberry on virulence factors involved in Streptococcus mutans biofilm development and acidogenicity. PAC and FLAV, alone or in combination, inhibited the surface-adsorbed glucosyltransferases and F-ATPases activities, and the acid production by S. mutans cells. Furthermore, biofilm development and acidogenicity were significantly affected by topical applications of PAC and FLAV (P<0.05). Anthocyanins were devoid of any significant biological effects. The flavonols are comprised of mostly quercetin glycosides, and the PAC are largely A-type oligomers of epicatechin. Our data show that proanthocyanidins and flavonols are the active constituents of cranberry against S. mutans.

Pharmacodynamic interaction of warfarin with cranberry but not with garlic in healthy subjects1

Posted: December 17, 2010
Authors: Abdul MJM, Jiang X, Williams KM, Day RO, Roufogalis BD, Liauw WS, Xu H, McLachlan AJ.
Journal: Br J Pharmacol 154(8):1691-1700

Abstract: Background and purpose: Patients commonly take complementary medicines in conjunction with warfarin yet evidence supporting the safety or the risk of a herb–drug interaction is lacking. The aim of this study was to investigate the possible impact of two commonly used herbal medicines, garlic and cranberry, on the pharmacokinetics and pharmacodynamics of warfarin in healthy male subjects. Experimental approach: An open-label, three-treatment, randomized crossover clinical trial was undertaken and involved 12 healthy male subjects of known CYP2C9 and VKORC1 genotype. A single dose of 25mg warfarin was administered alone or after 2 weeks of pretreatment with either garlic or cranberry. Warfarin enantiomer concentrations, INR, platelet aggregation and clotting factor activity were measured to assess pharmacokinetic and pharmacodynamic interactions between warfarin and herbal medicines. Key results: Cranberry significantly increased the area under the INR–time curve by 30% when administered with warfarin compared with treatment with warfarin alone. Cranberry did not alter S- or R-warfarin pharmacokinetics or plasma protein binding. Co-administration of garlic did not significantly alter warfarin pharmacokinetics or pharmacodynamics. Both herbal medicines showed some evidence of VKORC1 (not CYP2C9) genotype-dependent interactions with warfarin, which is worthy of further investigation.Conclusions and implications: Cranberry alters the pharmacodynamics of warfarin with the potential to increase its effectssignificantly. Co-administration of warfarin and cranberry requires careful monitoring.

Synergism of cranberry phenolics with ellagic acid and rosmarinic acid for antimutagenic and DNA protection functions

Posted: December 17, 2010
Authors: Vattem DA, Jang HD, Levin R, Shetty K
Journal: J Food Biochem 30(1):98-116

Abstract: Several studies have shown the antimutagenic DNA protective functions of some naturally occurring phenolic phytochemicals. Emerging research also indicates that synergistic functionality of these phytochemicals in whole foods benefits the management of many diseases. This study investigated the potential antimutagenic properties of cranberry phenolics, ellagic acid (EA), rosmarinic acid (RA) and their synergistic interactions on enhancing the antimutagenic properties in Salmonella typhimurium tester system against the mutagens sodium azide and N-methyl-N'-nitro-N-nitrosoguanidine. The ability of these phytochemical treatments to protect oxidative damage to DNA was also investigated using the supercoiled DNA strand scission assay. The results showed that EA was most effective in inhibiting the mutations in S. typhimurium system, whereas RA and EA were equally effective in protecting the DNA from oxidative damage. In addition, the antimutagenic activity of cranberry powder (CP) made from juice extracts was significantly enhanced when 30% (w/w) of phenolics in CP was substituted with RA and EA, possibly because of synergistic redox modulation that can influence mutagen function. It was also suggested that the synergistic mixture of cranberry phenolics with RA could also be protecting the cell from mutations by modulating the DNA repair systems

A double-blind, randomized, placebo-controlled trial of cranberry supplements in multiple sclerosis

Posted: December 16, 2010
Authors: McGuinness SD, Krone R, Metz LM, et al
Journal: J Neurosci Nurs 34(1):4-7

Abstract: Cranberry cocktail has been reported to reduce bacteriuria and pyuria in elderly women and self-reported urinary tract infection (UTI) in young female undergraduates, but commercially prepared cranberry concentrate supplements have never been evaluated in multiple sclerosis (MS) patients with neurogenic bladder. The purpose of this study was to determine whether one 8,000-mg cranberry concentrate supplement daily could prevent UTI in MS participants with bladder symptoms. We conducted a double-blind, randomized, placebo-controlled longitudinal trial of cranberry supplement versus placebo with participants who have MS. After informed consent had been obtained from the participants, baseline data were collected and participants were randomized to receive either one cranberry supplement or placebo daily for 6 months. The sample consisted of 135 participants. In the cranberry group 34.6% of participants failed (i.e., developed a UTI) versus 32.4% in the control group (p = .849). Not all cranberry supplements have been found to contain proanthocyanidins, the active ingredient of cranberries. Because there is no way for the consumer to distinguish supplements that contain proanthocyanidins from those that do not, taking juice or whole cranberries may be preferrable.

Cranberry extract and quercetin modulate the expression of cyclooxygenase-2 (COX-2) and I kappa B alpha in human colon cancer cells

Posted: December 16, 2010
Authors: Narayansingh R, Hurta RAR
Journal: J Sci Food Agr 89(3):542-547

Abstract: BACKGROUND: Cranberry (Vaccinium marcocarpon) fruit and quercetin, a major flavonoid found in cranberries, are likely contributors to chemoprevention, and their anti-inflammatory activities may play a potential role in colon cancer prevention. The aim of this study was to examine the effect of cranberry extract and quercetin on basal expression of cyclooxygenase-2 (COX-2) and I&#954;B&#945; as well as the effect on phorbol 12-myristate 13-acetate (PMA)-induced COX-2 expression in colon cancer cells.
RESULTS: HT-29 human colon adenocarcinoma cells were treated with various concentrations of cranberry extract or quercetin and/or PMA, and the protein expression of COX-2 and I&#954;B&#945; was determined. The results indicated that cranberry extract and quercetin decreased COX-2 expression and suppressed degradation of I&#954;B&#945; in unstimulated cells. In PMA-stimulated cells, cranberry extract was also able to decrease COX-2 expression and suppress degradation of I&#954;B&#945;.
CONCLUSION: The results suggest that a possible mechanism involved in the anti-cancer activity of cranberry and quercetin is partly mediated through its anti-inflammatory action. These findings indicate that cranberry and quercetin may reduce the risk of colon cancer possibly by suppressing inflammatory responses.

Effects of cranberry extracts and ursolic acid derivatives on P-fimbriated Escherichia coli, COX-2 activity, pro-inflammatory cytokine release and the NF-kappabeta transcriptional response in vitro

Posted: December 16, 2010
Authors: Huang Y, Nikolic D, Pendland S, Doyle BJ, Locklear TD, Mahady GB
Journal: Pharmaceut Biol 47(1):18-25

Abstract: Cranberry, the fresh or dried ripe fruit of Vaccinium macrocarpon Ait. (Ericaceae), is currently used as adjunct therapy for the prevention and symptomatic treatment of urinary tract infections. Data from clinical trials suggest that extracts of cranberry or cranberry juice reduce the bacterial load of E. coli and also suppress the inflammatory symptoms induced by E. coli infections. A methanol extract prepared from 10 kg of dehydrated cranberries did not directly inhibit the growth of E coli strains ATCC 700336 or ATCC 25922 in concentrations up to 256 mug/mL in vitro. However, the methanol extract (CR-ME) inhibited the activity of cyclooxygenase-2, with an IC(50) of 12.8 mug/mL. Moreover, CR-ME also inhibited the NF-kappabeta transcriptional activation in human T lymphocytes with an IC(50) of 19.4 mug/mL, and significantly (p < 0.01) inhibited the release of interleukin (IL)-1beta, IL-6, IL-8 and tumor necrosis factor-alpha from E. coli lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells in vitro, at a concentration of 50 mug/mL. The extract had no effect on inducible nitric oxide synthase activity in the murine macrophage cell line RAW 264.7. The compounds responsible for this activity were identified using a novel LC-MS based assay as ursolic acid and ursolic acid derivatives. Taken together, these data suggest CR-ME and its constituent chemical compounds target specific pathways involved in E. coli-induced inflammation.

Effects of ginger and cranberry

Posted: December 16, 2010
Authors: Liburt NR, McKeever KH, Streltsova JM, Franke WC, Gordon ME, Filho HCM, Horohov DW, Rosen RT, Ho CT, Singh AP, Vorsa N.
Journal: Comp Exerc Physiol 6(4):157-169

Abstract: This study hypothesized that ginger (Zingiber officinale) and cranberry (Vaccinium macrocarpon) extracts would alter the physiological response to exercise as well as markers of muscle damage, and mRNA expression for the inflammatory cytokines tumour necrosis factor-a (TNF-a), interferon-g (IFN-g) and interleukin-6 (IL-6) after an exhaustive bout of exercise in horses. Nine unfit Standardbred mares (age 10 ^ 4 years, ,450 kg) completed three graded exercise tests (GXTs) in a crossover design, where they were assigned to the initial order of treatment in a randomized fashion. The GXTs were conducted between 07.00 and 12.00 hours, 7 days apart. Mares received either water (2 l), cranberry (,30 g in 2 l of water) or ginger (,30 g in 2 l of water) extract 1 h prior to testing. Blood samples were taken prior to dosing (pre-exercise), at the end of each step of the GXT, at the end of the exercise and at 2, 5 and 30 min, 1, 2, 4 and 24 h post-GXT. Plasma total protein (TP) concentration and haematocrit (HCT) were analysed immediately following the tests. Analysis of creatine kinase (CK) and aspartate aminotransferase (AST) was done commercially. There was no effect of treatment (P > 0.05) on VO2max, run-time to fatigue, core temperature, TP or HCT. CK was substantially elevated (P < 0.05) in the ginger group at 4 h post-GXT. All CK levels returned to baseline 24 h post-GXT. No change (P > 0.05) was noted in AST. A slight increase (P < 0.05) in CK was seen in all groups at 2 h post-GXT. The cranberry group had significantly lower TNF-a mRNA expression than the control and ginger groups. Ginger appeared to influence (P < 0.05) the upregulation and expression of IFN-g mRNA at 30 min post-GXT, but, more strikingly, significantly decreased recovery time defined as the time for VO2 to recover from the peak observed at fatigue to a post-exercise plateau (ginger = 101 ± 3 s, water = 130 ± 14 s, cranberry = 131 ± 16 s). No effect of treatment or exercise (P > 0.05) was seen on IL-6 mRNA expression. Results suggest that cranberry extract blunts the upregulation and expression of TNF-a mRNA, while ginger extract reduces cardiovascular recovery time in horses completing a short, exhaustive bout of exercise.

Cranberry Juice Fails to Prevent Recurrent

Posted: December 12, 2010
Authors: Barbosa-Cesnik C, Brown MB, Buxton M, Zhang L, DeBusscher J,Foxman B
Journal: Clin Infect Dis 52(1):23–30

Abstract: Background. A number of observational studies and a few small or open randomized clinical trials suggest that
the American cranberry may decrease incidence of recurring urinary tract infection (UTI).
Methods. We conducted a double-blind, placebo-controlled trial of the effects of cranberry on risk of recurring
UTI among 319 college women presenting with an acute UTI. Participants were followed up until a second UTI or
for 6 months, whichever came first. A UTI was defined on the basis of the combination of symptoms and a urine
culture positive for a known uropathogen. The study was designed to detect a 2-fold difference between treated and
placebo groups, as was detected in unblinded trials. We assumed 30% of participants would experience a UTI during
the follow-up period.
Results. Overall, the recurrence rate was 16.9% (95% confidence interval, 12.8%–21.0%), and the distribution
of the recurrences was similar between study groups, with the active cranberry group presenting a slightly higher
recurrence rate (20.0% vs 14.0%). The presence of urinary symptoms at 3 days, 1–2 weeks, and at >1 month was
similar between study groups, with overall no marked differences.
Conclusions. Among otherwise healthy college women with an acute UTI, those drinking 8 oz of 27% cranberry
juice twice daily did not experience a decrease in the 6-month incidence of a second UTI, compared with those
drinking a placebo.

Can cranberry supplementation benefit adults with type 2 diabetes?

Posted: November 22, 2010
Authors: Chambers BK, Camire ME
Journal: Diabetes Care 26(9):2695-6

Abstract: "Adults controlling their type 2 diabetes through diet alone were recruited from the Bangor, Maine, community. Fourteen subjects (aged 57.9 [+ or -] 10.6 years, 6 women, 8 men, duration of diabetes 6.0 [+ or -] 8.5 years) were randomized to the cranberry group; 13 subjects (aged 52.6 [+ or -] 13.7 years, 6 women, 7 men, duration of diabetes 4.1 [+ or -] 4.9 years) were assigned to the placebo group. Subjects consumed six capsules filled with either cranberry juice concentrate powder or a placebo daily for 12 weeks. Six capsules were equivalent to a 240-ml serving of cranberry juice cocktail. The artificially colored placebo mimicked the cranberry powder in all respects but flavonoid content. Subjects were asked to discontinue use of dietary supplements, but no other diet and lifestyle changes were made during the study.

More than one-half of the subjects had good control of blood glucose levels (<7.0 mmol/l) at the beginning of the study. No differences were found between the treatment groups in fasting serum glucose, Hb[A.sub.1c], fructosamine, triglyceride, or HDL or LDL levels after 6 and 12 weeks. Placebo subjects had higher insulin values throughout the study (160 [+ or -] 167 vs. 86 [+ or -] 51 pmol/l at week 12, P < 0.05). Different effects might be seen in subjects with poor glucose control, individuals with type 1 diabetes, or people who use medications to control their type 2 diabetes. "

Cranberry constituents affect fructosyltransferase expression in Streptococcus mutans

Posted: November 22, 2010
Authors: Feldman M, Weiss E, Shemesh M, Ofek I, Bachrach G, Rozen R, Steinberg D
Journal: Alternative Ther Health Med 15(2):32-8

Abstract: CONTEXT: Cranberry juice has long been recognized in folk medicine as a therapeutic agent, mainly in urinary tract infections. Its proposed mechanism of action is antiadhesion of bacteria.

OBJECTIVE: Investigation of the potential antiadhesion effect of nondialyzed material of cranberry (NDM) via its influence on secretion, gene expression, and promoter activity of the fructosyltransferase (FTF), which is among the extracellular enzymes associated with dental biofilm formation and pathogenesis of oral bacteria.

MAIN OUTCOME MEASURES: Secretion of FTF from Streptococcus mutans, in the presence of NDM, was measured by immunoblotting and confocal scanning laser microscopy. Its influence on ftf gene expression was determined by reverse transcription followed by real-time RT-PCR. The luciferase assay was used to detect bioluminescence expressed by the ftf promoter activity of bacteria exposed to NDM.

RESULTS: NDM at concentrations between 0.2/mL and 1mg/mL significantly (P<.05) decreased secretion of extracellular FTF, as well as down-regulated ftf expression in a dose-dependent manner. NDM also markedly reduced the luciferase activity under the ftf promoter.

Interference of cranberry constituents in cell-cell signaling system of Vibrio harveyi

Posted: November 22, 2010
Authors: Feldman M, Weiss EI, Ofek I, Steinberg D
Journal: Curr Microbiol 59(4):469-74

Abstract: Cranberry juice has long been recognized in folk medicine as a therapeutic agent, mainly in urinary track infections. It acts as an antibiofilm agent against various pathogens. Quorum sensing is process where bacteria communicate with each other via signal molecules known as autoinducers. This process is strongly involved in various bacterial pathological and physiological pathways. Various strains of Vibrio harveyi bacteria were incubated with different concentrations of nondialyzable material of cranberry (NDM) with or without addition of exogenous autoinducer. Bioluminescence regulated by the autoinducers was measured in GENios reader. Effect of NDM alone or NDM supplemented with autoinducer on quorum sensing was determined as change in bioluminescence in each treated sample compared to appropriate control in every strain. Using model of V. harveyi, we found an inhibitory effect of cranberry constituents on bacterial signaling system. This effect was reversible, since exogenous autoinducer was able to recover bioluminescence which was decreased by NDM. We hypothesized that cranberry NDM interacts with V. harveyi quorum sensing by competition with autoinducer

Antioxidant levels of common fruits, vegetables, and juices versus protective activity against in vitro ischemia/reperfusion.

Posted: November 19, 2010
Authors: Bean H, Schuler C, Leggett RE and Levin RM
Journal: Int Urol Nephrol 42(2):409-15

Abstract: It is well known that antioxidants present in various fruits, vegetables, and juices have the potential to protect the urinary bladder from free radical damage. What is not well understood, however, is how well antioxidant activities detected by chemical methods such as the CUPRAC assay for total antioxidant activity (TAA) predict the level of physiological protection available. It is hypothesized that the level of antioxidant reactivity found by the CUPRAC assay will positively correlate with increased protection in a model of in vitro ischemia/reperfusion. To test this hypothesis, the CUPRAC assay was utilized to determine the antioxidant reactivity of a series of fruits, vegetables, and juices, and the results were compared to the protective ability of selected juices in an established in vitro rabbit bladder model of ischemia/reperfusion. The results of the CUPRAC test showed that cranberry juice had the highest level of antioxidant reactivity, blueberry juice had an intermediate activity, and orange juice had the lowest. It was determined, however, that contrary to the hypothesis, the orange juice was significantly more potent in protecting the bladder against ischemia/reperfusion damage than either blueberry or cranberry juice. Thus, it is concluded that chemical tests for TAA do not necessarily correlate with their physiological activity.

Loss of fimbrial adhesion with the addition of Vaccinum macrocarpon to the growth medium of P-fimbriated Escherichia coli

Posted: November 19, 2010
Authors: Ahuja S, Kaack B, Roberts J.
Journal: J Urol 159(2):559-62

Abstract: PURPOSE: Vaccinium macrocarpon--the American cranberry--irreversibly inhibits the expression of P-fimbriae of E. coli. Further effects on the function and expression of P-fimbriae were studied by growing P-fimbriated E. coli in solid media laced with cranberry juice.

METHODS: Cranberry concentrate at pH 7.0 was added to CFA medium to a final concentration of 25%. E. coli strains JR1 and DS17 were plated on this medium with a plain CFA control and incubated at 37C. Cultures were tested for ability to agglutinate P-receptor specific beads. Bacteria were washed in PBS and agglutination retested. Cultures were also replated on plain CFA agar and rechecked for their ability to agglutinate. Transmission electron micrographs were performed on positive control and test bacteria.

RESULTS: For E. coli strain JR1, P-fimbrial agglutination was inhibited after the third plating. DS17 was fully inhibited after the second plating. Washing in PBS did not affect agglutination, but replating on CFA agar allowed agglutination to recur. Electron micrographic study of control populations confirmed fimbriae. Fully inhibited bacteria had a 100% reduction in expression of fimbriae. Additionally, inhibited bacteria showed cellular elongation.

CONCLUSIONS: Cranberry juice irreversibly inhibits P-fimbriae. Electron micrographic evidence suggests that cranberry juice acts on the cell wall preventing proper attachment of the fimbrial subunits or as a genetic control preventing the expression of normal fimbrial subunits or both.

A high molecular mass constituent of cranberry juice inhibits helicobacter pylori adhesion to human gastric mucus.

Posted: November 17, 2010
Authors: Burger O, Ofek I, Tabak M, Weiss EI, Sharon N, Neeman I
Journal: FEMS Immunol Med Microbiol 29(4):295-301

Abstract: Because previous studies have shown that a high molecular mass constituent of cranberry juice inhibited adhesion of Escherichia coli to epithelial cells and coaggregation of oral bacteria, we have examined its effect on the adhesion of Helicobacter pylori to immobilized human mucus and to erythrocytes. We employed three strains of H. pylori all of which bound to the mucus and agglutinated human erythrocytes via a sialic acid-specific adhesin. The results showed that a high molecular mass constituent derived from cranberry juice inhibits the sialic acid-specific adhesion of H. pylori to human gastric mucus and to human erythrocytes.

Composition of a chemopreventive proanthocyanidin-rich fraction from cranberry fruits responsible for the inhibition of 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced ornithine decarboxylase (ODC) activity.

Posted: November 17, 2010
Authors: Kandil FE, Smith MA, Rogers RB, Pépin MF, Song LL, Pezzuto JM, Seigler DS
Journal: J Agric Food Chem 50(5):1063-9

Abstract: Phenolics from the American cranberry (Vaccinium macrocarpon) were fractionated into a series of proanthocyanidins and other flavonoid compounds by vacuum chromatography on a hydrophilic, porous polyvinylic gel permeation polymer. Antioxidant activity was not restricted to a particular class of components in the extract but was found in a wide range of the fractions. Significant chemopreventive activity, as indicated by an ornithine decarboxylase assay, was localized in one particular proanthocyanidin-rich fraction from the initial fractionation procedure. Further fractionation of the active anticarcinogenic fraction revealed the following components: seven flavonoids, mainly quercetin, myricetin, the corresponding 3-O-glycosides, (-)-epicatechin, (+)-catechin, and dimers of both gallocatechin and epigallocatechin types, and a series of oligomeric proanthocyanidins.

Cranberry juice and urinary-tract health: science supports folklore

Posted: November 17, 2010
Authors: Henig YS, Leahy MM
Journal: Nutrition 16(7-8):684-7

Abstract: In the 20th century, the health benefit most often attributed to the cranberry is its role in maintaining urinary-tract health. A 1998 study by the International Food Information Council (personal communication) indicated that 47% of consumers surveyed were aware of a link between cranberry juice and urinary-tract health.

Cranberry PACs and triterpenoids: anti-cancer activities in colon tumor cell lines

Posted: November 17, 2010
Authors: Liberty AM, Amoroso JW, Neto CC, Hart PE, Patil B, Murano P, Amiot-Carlin MJ
Journal: Acta Hort 841:61-66

Abstract: Phytochemicals from North American cranberry (Vaccinium macrocarpon) fruit may be expected to influence the development of colon cancer. Tissue-culture models were used to assess effects of cranberry components on cell proliferation, apoptosis, and the formation of tumor cell colonies. Several phytochemicals and fractions isolated from whole cranberry fruit were previously reported to inhibit growth and proliferation of breast, colon, prostate, and other tumor cell lines. In HT-29 and HCT116 colon tumor cell lines, cranberry proanthocyanidins (PACs) and ursolic acid inhibited the formation of tumor colonies over a two week period in a dose-dependent manner. Apoptosis is likely to play a role in limiting tumor cell proliferation. In HT-29 and HCT116 colon tumor cell lines treated with either ursolic acid or a cranberry proanthocyanidin fraction, the percentage of cells undergoing apoptosis increased in a dose-dependent manner. Thus, cranberry phytochemicals have the potential to limit carcinogenesis.

Effect of cranberry juice on urinary pH

Posted: November 17, 2010
Authors: Kinney AB, Blount M.
Journal: Nurs Res 28(5):287-90

Abstract: Twenty-one female and 19 male subjects who had normal physical and laboratory examinations were randomly assigned into four groups of 10 subjects each. Each group was then randomly assigned a number (150, 180, 210, 240) which determined the amount of cranberry juice, in milliliters, members of that group would ingest with each meal during the experimental phase of the study. The study took place over a 12-day period. A one-group before-and-after design was used, with each subject serving as his or her own control. Diet was controlled; menus on days 1 through 6 were repeated on days 7 through 12 with the addition of cranberry juice at each meal. Subjects used nitrazine pH tape to measure the pH of midstream urine at each voiding. There were significant (.01 level) differences in mean urinary pH between each control group and its corresponding experimental group. Anticipated problems with increased number of bowel movements, weight gain, increased voiding frequency, and subject pH measurement inaccuracy did not occur.

Effect of cranberry juice on urinary pH in older adults

Posted: November 17, 2010
Authors: Jackson B, Hicks LE
Journal: Home Healthc Nurse 15(3):198-202

Abstract: Most research suggests that ingestion of cranberry juice may be useful in preventing urinary tract infections. This pilot study examines the effect of drinking moderate amounts of commercially available cranberry juice cocktail on urinary pH in older, institutionalized adults. The results of the study have implications for home care nurses who have similar patients in their case loads.

Effect of cranberry juice on urine

Posted: November 17, 2010
Authors: Kahn HD, Panariello VA, Saeli J, Sampson JR, Schwartz E
Journal: J Am Diet Assoc 51(3):251-4

Abstract: The purpose of this study was to quantitate the effect of cranberry juice ingestion on urinary acidification and calcium excretion, in a diet-controlled situation.

Effect of diet on serum accumulation and renal excretion of aryl acids and secretory activity in normal and uremic man

Posted: November 17, 2010
Authors: Cathcart-Rake W, Porter R, Whittier F, Stein P, Carey M, Grantham J
Journal: Am J Clin Nutr 28(10):1110-5

Abstract: The influence of diet on aryl acid metabolism was determined in normal and azotemic subjects. Aryl acid content of serum and urine was estimated by fluorometry in relation to hippuric acid as a standard (FI-Hipp). Secretory activity, a reflection of the biological potency of aromatic acids in serum and urine, was determined by bioassay. The urinary excretion of FI-Hipp and secretory activity of five normal persons on an ad lib diet was 0.78 and 2.25 mM/day, respectively; similar values were observed in two subjects with chronic renal insufficiency. Subjects were fed prunes and cranberries, since these foods contain abundant quantities of hippurate precursors. Prunes 1.5 g/kg body weight, caused the urinary excretion of both FI-Hipp and secretory activity to increase about tenfold in normal and azotemic subjects. Prune feeding caused the serum levels of FI-Hipp and secretory activity to increase about threefold. Cranberries increased the renal excretion of FI-Hipp and secretory activity as did the ingestion of a beverage containing benzoate as a preservative. On the basis of these studies it is clear that diet is an important determinant of the load of aryl acids for urinary excretion; in patients with renal insufficiency the ingestion of foods containing precursors may cause serum level of biologically active aryl acids to increase strikingly.

Effects of cranberry powder on serum lipid profiles and biomarkers of oxidative stress in rats fed an atherogenic diet

Posted: November 17, 2010
Authors: Kim MJ, Jung HN, Kim KN, Kwak HK
Journal: Nutr Res Pract 2(3):158-64

Abstract: This study investigated that the antioxidative effect of freeze-dried cranberry powder against protein and lipid oxidation and ameliorative effect of serum lipid profile in rat fed atherogenic diet. Six weeks old male Sprague-Dawley rats were divided into the following four groups: normal diet group with 5% corn oil (control), atherogenic diet group with 5% corn oil, 10% lard, 1% cholesterol, and 0.5% sodium cholate (HFC), atherogenic plus 2% cranberry powder diet group (HFC + C2), and atherogenic plus 5% cranberry powder diet group (HFC + C5), and respective diet and water were fed daily for 6 weeks. After the experimental period, the serum lipid profile, such as total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglyceride, ferric reducing ability of plasma (FRAP), plasma phenolics content, superoxide dismutase (SOD) activity, serum protein carbonyl and thiobarbituric acid reactive substances (TBARS) levels were examined. Total phenolic compound and total flavonoid levels in freeze-dried cranberry powder were 9.94 mg/g and 8.12 mg/g, respectively. Serum total cholesterol and LDL-cholesterol levels were not significantly different for cranberry powder treatment, but serum HDL-cholesterol level was significantly increased in HFC + C5 group compared with HFC group. Plasma FRAP value tended to be increased by cranberry powder treatment though there was no significant difference. Plasma total phenol concentrations and SOD activities were not significantly different among all groups. Serum protein carbonyl and TBARS levels were significantly decreased in HFC + C5 group compared with HFC group. Overall results suggested that freeze-dried cranberry powder might have the serum lipid improving effect, as well as antioxidative effect demonstrated by its protective effect against protein and lipid oxidation.

Impact of cranberry juice and proanthocyanidins (PACs) on the zeta potentials of Escherichia coli and uroepithelial cells

Posted: November 17, 2010
Authors: Liu YT, Pinzon-Arango PA, Camesano TA, Patil B, Murano P, Amiot-Carlin MJ
Journal: Acta Hort 841:259-264

Abstract: Bacterial surface properties, such as electrostatic potential play an important role in the bacterial adhesion process, which is widely considered as the first step leading to infections. Cranberry juice and its compound A-type proanthocyanidins (PACs) were used to treat two isogenic E. coli strains and human uroepithelial cells and the zeta potentials were measured at several cranberry juice or PACs concentrations. P fimbriae were shown to be slightly positively charged, which helps bacteria adhere onto mammalian cells. PACs significantly decreased the bacterial zeta potentials from -15.6 ± 0.9 mV to -41.5 ± 0.7 mV, which increased the electrostatic repulsion forces to mammalian cells. Cranberry juice treatment did not change bacterial zeta potentials significantly, ranging from -14.9 ± 1.8 mV to -16.3 ± 0.8 mV. The abundance of other compounds in cranberry juice may have blocked the influence of PACs, considering the relatively small proportion of PACs in cranberry juice.

In vitro anticancer activity of fruit extracts from Vaccinium species

Posted: November 17, 2010
Authors: Bomser J, Madhavi DL, Singletary K, Smith MA
Journal: Planta Med 62(3):212-6

Abstract: Fruit extracts of four Vaccinium species (lowbush blueberry, bilberry, cranberry, and lingonberry) were screened for anticarcinogenic compounds by a combination of fractionation and in vitro testing of their ability to induce the Phase II xenobiotic detoxification enzyme quinone reductase (QR) and to inhibit the induction of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine synthesis, by the tumor promoter phorbol 12-myristate 13-acetate (TPA). The crude extracts, anthocyanin and proanthocyanidin fractions were not highly active in QR induction whereas the ethyl acetate extracts were active QR inducers. The concentrations required to double QR activity (designated CDqr) for the ethyl acetate extracts of lowbush blueberry, cranberry, lingonberry, and bilberry were 4.2, 3.7, 1.3, and 1.0 microgram tannic acid equivalents (TAE), respectively, Further fractionation of the bilberry ethyl acetate extract revealed that the majority of inducer potency was contained in a hexane/chloroform subfraction (CDqr = 0.07 microgram TAE). In contrast to their effects on QR, crude extracts of lowbush blueberry, cranberry, and lingonberry were active inhibitors of ODC activity. The concentrations of these crude extracts needed to inhibit ODC activity by 50% (designated IC50) were 8.0, 7.0, and 9.0 micrograms TAE, respectively. The greatest activity in these extracts appeared to be contained in the polymeric proanthocyanidin fractions of the lowbush blueberry, cranberry, and lingonberry fruits (IC50 = 3.0, 6.0, and 5.0 micrograms TAE, respectively). The anthocyanidin and ethyl acetate extracts of the four Vaccinium species were either inactive or relatively weak inhibitors of ODC activity. Thus, components of the hexane/chloroform fraction of bilberry and of the proanthocyanidin fraction of lowbush blueberry, cranberry, and lingonberry exhibit potential anticarcinogenic activity as evaluated by in vitro screening tests.

In vitro binding of bile acids by blueberries (Vaccinium spp.), plums (Prunus spp.), prunes (Prunus spp.), strawberries (Fragaria x ananassa), cherries (Malpighia punicifolia), cranberries (Vaccinium macrocarpon) and apples (Malus sylvestris)

Posted: November 17, 2010
Authors: Kahlon TS, Smith GE
Journal: Food Chem 100(3):1182-1187

Abstract: The in vitro binding of bile acids by blueberries (Vaccinium spp.), plums (Prunus spp.), prunes (Prunus spp.), strawberries (Fragaria x ananassa), cherries (Malpighia punicifolia) cranberries (Vaccinium macrocarpon) and apples (Malus sylvestris) was determined using a mixture of bile acids secreted in human bile at a duodenal physiological pH of 6.3. Six treatments and two blank incubations were conducted to testing various fresh raw fruits on an equal dry matter basis. Considering cholestyramine (bile acid binding, cholesterol lowering drug) as 100% bound, the relative in vitro bile acid binding on dry matter (DM), total dietary fibre (TDF) and total polysaccharides (PCH) basis was for blueberries 7%, 47% and 25%; plums 6%, 53% and 50%; prunes 5%, 50% and 14%; strawberries 5%, 23% and 15%; cherries 5%, 37% and 5%; cranberries 4%, 12% and 7%; and apple 1%, 7% and 5%, respectively. Bile acid binding on DM basis for blueberries was significantly (P<=0.05) higher than all the fruits tested. The bile acid binding for plums was similar to that for prunes and strawberries and significantly higher than cherries, cranberries and apples. Binding values for cherries and cranberries were significantly higher than those for apples. These results point to the relative health promoting potential of blueberries > plums=prunes=strawberries=cherries=cranberries > apples as indicated by their bile acid binding on DM basis. The variability in bile acid binding between the fruits tested maybe related to their phytonutrients (antioxidants, polyphenols, hydroxycinnamic acids, flavonoids, anthocyanins, flavonols, proanthocyanidins, catechins), structure, hydrophobicity of undigested fractions, anionic or cationic nature of the metabolites produced during digestion or their interaction with active binding sites. Inclusion of blueberries, plums, prunes, strawberries, cherries and cranberries in our daily diet as health promoting fruits should be encouraged. Animal studies are planned to validate in vitro bile acid binding of fruits observed herein to their potential of atherosclerosis amelioration (lipid and lipoprotein lowering) and cancer prevention (excretion of toxic metabolites).

Influence of cranberry juice on attachment of Escherichia coli to glass

Posted: November 17, 2010
Authors: Allison DG, Cronin MA, Hawker J, Freeman S
Journal: J Basic Microbiol 40(1):3-6

Abstract: An extract from fresh cranberries was shown to decrease the strength of attachment of Escherichia coli to glass coverslips when incubated together for 2 h. Pre-conditioning of the surface prior to biofilm formation also significantly weakened the strength of attached cells.

Media acidification by Escherichia coli in the presence of cranberry juice

Posted: November 17, 2010
Authors: Johnson BJ, Lin B, Rubin RA, Malanoski AP
Journal: BMC Res Notes 2:226.

Abstract: BACKGROUND: The inhibition of Escherichia coli growth in the presence of Vaccinium macrocarpon has been extensively described; however, the mechanisms of this activity are not well characterized.

FINDINGS: Here, E. coli was grown in media spiked with cranberry juice. The growth rate and media pH were monitored over more than 300 generations. The pH of the growth media was found to decrease during cell growth. This result was unique to media spiked with cranberry juice and was not reproduced through the addition of sugars, proanthocyanidins, or metal chelators to growth media.

CONCLUSION: This study demonstrated that factors other than sugars or proanthocyanidins in cranberry juice result in acidification of the growth media. Further studies are necessary for a complete understanding of the antimicrobial activity of cranberry products.

Microbial inhibitors of cranberries

Posted: November 17, 2010
Authors: Marwan AG, Nagel CW
Journal: J Food Sci 51(4):1009-1013

Abstract: An ethanolic extract of Cranberry exerted a significant antimicrobial effect on Saccharomyces bayanus and Pseudomonas fluorescens. The antimicrobial properties of cranberries were due to a number of factors. First, the low pH (2.6) inhibited many microorganisms per se, and its effect on the dissociation of benzoic acid made the inhibition more drastic. Secondly, after raising the pH to 5.2, cranberry juice still did not support the growth of S. bayanus. Growth did occur at pH 5.2 after 0.3% yeast nitrogen base was added. Thirdly, proanthocyanidins and flavonols were found to be the major microbial inhibitors other than benzoic acid. The results showed that proanthocyanidins provided 21.3% of the inhibition, the flavonols 18.5% and benzoic acid 15.6%.

New support for a folk remedy: cranberry juice reduces bacteriuria and pyuria in elderly women

Posted: November 17, 2010
Authors: Fleet JC
Journal: Nutr Rev 52(5):168-70

Abstract: Cranberry juice has developed a following as a simple, nonpharmacologic means to reduce or treat urinary tract infections, yet the scientific basis for such a claim has been lacking. A new study suggests that bacterial infections (bacteriuria) and associated influx of white blood cells into the urine (pyuria) can be reduced by nearly 50% in elderly women who drink 300 mL of cranberry juice cocktail each day over the course of a 6-month study. The results of this study suggest that consumption of cranberry juice is more effective in treating than preventing bacteriuria and pyuria. Along with earlier reports on the ability of cranberry juice to inhibit bacterial adherence to urinary epithelial cells in cell culture, this new work suggests that drinking cranberry juice each day may be clinically useful. Additional work must be conducted, however, to more completely define the efficacy of cranberry juice.

Novel concentrated cranberry liquid blend, UTI-STAT with Proantinox, might help prevent recurrent urinary tract infections in women

Posted: November 17, 2010
Authors: Efros M, Bromberg W, Cossu L, Nakeleski E, Katz AE
Journal: Urology 76(4):841-5

Abstract: OBJECTIVES: To determine the safety, tolerability, maximal tolerated dose, and efficacy of a concentrated cranberry liquid blend, UTI-STAT with Proantinox, in female patients with a history of recurrent urinary tract infections (rUTIs).

METHODS: The study agent was administered orally at 15, 30, 45, 60, and 75 mL daily for 12 weeks to women with a history of 2.78 ± 0.73 rUTIs <6 months. Blood and urine samples were collected at baseline and weeks 4 and 12. The women took daily doses of the agent. The primary endpoints were the safety, tolerability, and maximal tolerated dose. The secondary endpoints were the efficacy with regard to rUTI and quality-of-life (QOL) symptoms.

RESULTS: A total of 28 subjects were included in the study. Of these 28 women, the data from 23 were analyzable. The average age was 46.5 ± 12.8 years. The maximal tolerated dose of UTI-STAT was 75 mL/d, and the recommended dose was set at 60 mL/d. The secondary endpoints demonstrated that only 2 (9.1%) of 23 reported a rUTI, a markedly better rate than the historical data. At 12 weeks, the reduction in worry about rUTIs and increased QOL with regard to the physical functioning domain and role limitations from physical health domain, as measured by the Medical Outcomes Study short-form 36-item questionnaire, were significant (P = .0097). A lower American Urological Association Symptom Index indicating greater QOL was also significant (P = .045).

CONCLUSIONS: The novel concentrated cranberry liquid blend showed a good safety profile and tolerability in both pre- and postmenopausal women with history of rUTIs. The secondary endpoints demonstrated its effectiveness in reducing the incidence of rUTI and increasing QOL. Given this evidence, supplementation might be beneficial in the prevention of rUTIs in this population.

Proanthocyanidins from the American Cranberry (Vaccinium macrocarpon) inhibit matrix metalloproteinase-2 and matrix metalloproteinase-9 activity in human prostate cancer cells via alterations in multiple cellular signalling pathways.

Posted: November 17, 2010
Authors: Déziel BA, Patel K, Neto C, Gottschall-Pass K, Hurta RA
Journal: J Cell Biochem 111(3):742-54

Abstract: Prostate cancer is one of the most common cancers in the Western world, and it is believed that an individual's diet affects his risk of developing cancer. There has been an interest in examining phytochemicals, the secondary metabolites of plants, in order to determine their potential anti-cancer activities in vitro and in vivo. In this study we document the effects of proanthocyanidins (PACs) from the American Cranberry (Vaccinium macrocarpon) on matrix metalloproteinase (MMP) activity in DU145 human prostate cancer cells. Cranberry PACs decreased cellular viability of DU145 cells at a concentration of 25&#8201;µg/ml by 30% after 6&#8201;h of treatment. Treatment of DU145 cells with PACs resulted in an inhibition of both MMPs 2 and 9 activity. PACs increased the expression of TIMP-2, a known inhibitor of MMP activity, and decreased the expression of EMMPRIN, an inducer of MMP expression. PACs decreased the expression of PI-3 kinase and AKT proteins, and increased the phosphorylation of both p38 and ERK1/2. Cranberry PACs also decreased the translocation of the NF-&#954;B p65 protein to the nucleus. Cranberry PACs increased c-jun and decreased c-fos protein levels. These results suggest that cranberry PACs decreases MMP activity through the induction and/or inhibition of specific temporal MMP regulators, and by affecting either the phosphorylation status and/or expression of MAP kinase, PI-3 kinase, NF-&#954;B and AP-1 pathway proteins. This study further demonstrates that cranberry PACs are a strong candidate for further research as novel anti-cancer agents.

The effect of cranberry juice on the presence of bacteria and white blood cells in the urine of elderly women. What is the role of bacterial adhesion?

Posted: November 17, 2010
Authors: Avorn J
Journal: Adv Exp Med Biol 408:185-6


The effect of water, ascorbic acid, and cranberry derived supplementation on human urine and uropathogen adhesion to silicone rubber.

Posted: November 17, 2010
Authors: Habash MB, Van der Mei HC, Busscher HJ, Reid G
Journal: Can J Microbiol 45(8):691-4

Abstract: In this study, urine was collected from groups of volunteers following the consumption of water, ascorbic acid, or cranberry supplements. Only ascorbic acid intake consistently produced acidic urine. Photospectroscopy data indicated that increased water consumption produced urine with lower protein content. Surface tension measurements of the collected urine showed that both water and cranberry supplementation consistently produced urine with surface tensions higher than the control or urine collected following ascorbic acid intake. These urine samples were also employed to study uropathogen adhesion to silicone rubber in a parallel plate flow chamber. Urine obtained after ascorbic acid or cranberry supplementation reduced the initial deposition rates and numbers of adherent Escherichia coli and Enterococcus faecalis, but not Pseudomonas aeruginosa, Staphylococcus epidermidis, or Candida albicans. Conversely, urine obtained from subjects with increased water intake vastly increased the initial deposition rates and numbers of adherent E. coli and E. faecalis (P < 0.05).

Efficacy of cranberry in prevention of urinary tract infection in a susceptible pediatric population

Posted: November 16, 2010
Authors: Foda MM, Middlebrook PF, Gatfield CT, Potvin G, Wells G, Schillinger JF
Journal: Can J Urol 2(1):98-102

Abstract: The objective of the study was to evaluate liquid cranberry products as prophylaxis against bacterial urinary tract infection in a pediatric neuropathic bladder population. Forty cases managed by clean intermittent catheterization with or without pharmacotherapy were enrolled in a randomized single-blind cross-over study. Subjects ingested 15 mL/kg/day of cranberry cocktail or water for six months followed by the reverse for another six months. Initial catheter urine samples and subsequent monthly and interim cultures were obtained. Associated symptoms were recorded along with follow-up attendance/compliance registry. The number of negative culture months to the number of months contributed was tabulated and compared between interventions. Individual, cumulative and antimicrobial subset analysis was performed. Twenty one patients completed the study;12 dropped out for reasons related to the cranberry (taste, caloric load and cost); seven patients dropped out for other reasons (parents too busy, death, no stated reason). Wilcoxon matched-pairs Signed-ranks analysis revealed no difference between intervention periods (2-tailed P=.5566 [whole group]; p=.2845 [antimicrobial subset]) with respect to infection. Fewer infections were observed in nine patients taking cranberry juice and in nine patients given water; no difference was noted in three. Liquid cranberry products, on a daily basis, at the dosage employed, did not have any effect greater than that of water in preventing urinary tract infections in this pediatric neuropathic bladder population.

Anti-Escherichia coli adhesin activity of cranberry and blueberry juices

Posted: November 15, 2010
Authors: Ofek I, Goldhar J, Sharon N
Journal: Adv Exp Med Biol 408:179-83.

Abstract: No abstract

Cranberry juice consumption may reduce biofilms on uroepithelial cells: pilot study in spinal cord injured patients

Posted: November 15, 2010
Authors: Reid G, Hsiehl J, Potter P, Mighton J, Lam D, Warren D and Stephenson J
Journal: Spinal Cord 39(1):26-30

Abstract: STUDY DESIGN: A pilot study of 15 spinal cord injured patients. Objective: To determine whether alteration of fluid intake and use of cranberry juice altered the bacterial biofilm load in the bladder. SETTING: London, Ontario, Canada. METHODS: Urine samples were collected on day 0 (start of study), on day 7 following each patient taking one glass of water three times daily in addition to normal diet, and on day 15 following each patient taking one glass of cranberry juice thrice daily. One urine sample was sent for culture and a second processed to harvest, examine by light microscopy and Gram stain non-squamous uroepithelial cells to generate bacterial adhesion per 50 cells data. RESULTS: The results showed that cranberry juice intake significantly reduced the biofilm load compared to baseline (P=0.013). This was due to a reduction in adhesion of Gram negative (P=0.054) and Gram positive (P=0.022) bacteria to cells. Water intake did not significantly reduce the bacterial adhesion or biofilm presence. CONCLUSION: The findings provide evidence in support of further, larger clinical trials into the use of functional foods, particularly cranberry juice, to reduce the risk of UTI in a patient population highly susceptible to morbidity and mortality associated with drug resistant uropathogens

Does cranberry juice have antibacterial activity?

Posted: November 15, 2010
Authors: Lee YL, Owens J, Thrupp L and Cesario TC
Journal: JAMA 283(13):1691

Abstract: No abstract - Methods: We tested a 5-fold concentrated preparation of the juice to simulate the cranberry concentrate currently available commercially. The concentrate was diluted 1:1 with trypticase soy broth and adjusted to a pH of 7.0 to ensure that the results would not be confounded by the acidity of the medium. We added an inoculum of approximately 104 colony-forming units per milliliter from an overnight culture of a variety of American Type Culture Collection–quality control strains both to plain broth and the broth to which the cranberry juice had been added. Both cultures were incubated at 35°C and bacterial counts performed in duplicate at 90 minutes and 24 hours.

Effect of american cranberry (Cysticlean) on Escherichia coli adherence to bladder epithelial cells. In vitro and in vivo study.

Posted: November 15, 2010
Authors: Risco E, Miguelez C, Sanchez de Badajoz E, Rouseaud A
Journal: Arch Esp Urol 63(6):422-30

Abstract: OBJECTIVES: The American cranberry proanthocyanidins (PACs) are the main responsible for its efficacy in urinary tract infections. Their mechanism of action is related to inhibition of Escherichia coli to urothelial cells. Cysticlean contains an extract of American cranberry which provides 118 mg of PACs per dose. The activity of Cysticlean tablets on Escherichia Coli adherence to bladder epithelial cells has been studied in vitro. Moreover, the activity of Cistyclean both in powder for oral suspension and tablets has been compared ex-vivo. METHODS: The rats received both Cysticlean preparations per orem, and urine from each animal was collected during the following 16 hours and preincubated with E. coli. Subsequently, bacteria were incubated with T24 cells. After 1 hour the number of bacteria adhered per cell was calculated. For the in vitro study, E. Coli preincubated at various concentrations of the products were incubated with T24 cells and the same process previously referred was carried out. RESULTS: Urine samples from rats taking Cysticlean powder for oral suspension and tablets (118 mg PACs/animal) showed an important inhibition of E. Coli adherence (83% and 52%respectively). The inferior dose of 59 mg PACs/animal also showed marked inhibition of E. Coli adherence (29% after Cysticlean tablets intake and 40% for powder). In vitro, Cysticlean showed inhibition of bacterial adherence in all tested concentrations: 5, 25 and 75 PACs mg/ml, diminishing the number og bacteria adhered to epithelial cells by 25%, 36% and 34% respectively. CONCLUSIONS: Cysticlean shows a significant inhibition of E. Coli adherence to urothelial cells. Cysticlean powder for suspensión preparation is more effective tha tablets. Cysticlean powder for suspensión is well tolerated, and compliance has been observed. Its use is very recommendable in pediatric urinary tract infection prophylaxis. Due to the variety of products with American cranberry extracts in the market, with different proanthocyanidins declared content, it would be interesting to compare their activity using established pharmacological methods.

Effects of blueberry and cranberry juice consumption on the plasma antioxidant capacity of healthy female volunteers

Posted: November 15, 2010
Authors: Pedersen CB, Kyle J, Jenkinson AM, Gardner PT, McPhail DB, Duthie GG
Journal: Eur J Clin Nutr 54(5):405-8

Abstract: OBJECTIVE: To assess whether consumption of 500 ml of blueberry juice or cranberry juice by healthy female subjects increased plasma phenolic content and antioxidant capacity. DESIGN: Latin square arrangement to eliminate ordering effects. After an overnight fast, nine volunteers consumed 500 ml of blueberry juice, cranberry juice or a sucrose solution (control); each volunteer participated on three occasions one week apart, consuming one of the beverages each time. Blood samples were obtained by venipuncture at intervals up to four hours after consumption of the juices. Urine samples were also obtained four hours after consuming the juice. RESULTS: Consumption of cranberry juice resulted in a significant increase in the ability of plasma to reduce potassium nitrosodisulphonate and Fe(III)-2,4, 6-Tri(2-pyridyl)-s-triazine, these measures of antioxidant capacity attaining a maximum after 60-120 min. This corresponded to a 30% increase in vitamin C and a small but significant increase in total phenols in plasma. Consumption of blueberry juice had no such effects. CONCLUSION: The increase in plasma antioxidant capacity following consumption of cranberry juice could mainly be accounted for by an increase in vitamin C rather than phenolics. This also accounted for the lack of an effect of the phenolic-rich but vitamin C-low blueberry juice.

Lack of effect of ascorbic acid, hippuric acid, and methenamine (urinary formaldehyde) on the copper-reduction glucose test in geriatric patients

Posted: November 15, 2010
Authors: Nahata MC, McLeod DC
Journal: J Am Geriatr Soc 28(5):230-3

Abstract: Ascorbic acid and hippuric acid (from cranberry juice) are commonly used to acidify the urine for the purpose of enhancing the degradation of therapeutic methenamine mandelate to urinary formaldehyde. A study was made of 27 nondiabetic geriatric patients with indwelling Foley catheters and chronic bacteriuria who were treated with methenamine mandelate (4 gm), ascorbic acid (4 gm), and cranberry cocktail (1 liter) daily. All of 972 urine samples showed formaldehyde in mean concentrations between 14 and 25 microgram/ml. No glucose was found when the urine was tested by the copper-reduction method. In vitro false positive reactions reported in the literature do not appear to be duplicated as an in vivo problem.

Potential of cranberry powder for management of hyperglycemia using in vitro models

Posted: November 15, 2010
Authors: Pinto Mda S, Ghaedian R, Shinde R, Shetty K
Journal: J Med Food 13(5):1036-44

Abstract: Aqueous solutions of two different cranberry powders (CP and CP-SAB) were evaluated for organic acids, sugars, total phenolics, antioxidant activity based on the 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay, and functionality such as in vitro inhibition of -amylase, -glucosidase, and angiotensin I-converting enzyme (ACE) relevant for potential management of hyperglycemia and hypertension linked to type 2 diabetes. The total phenolics content was 11 and 51 mg/g of sample dry weight for CP and CP-SAB, respectively. p-Coumaric acid and quercetin derivatives were the main phenolic compounds identified in the cranberry powders. CP-SAB had -glucosidase inhibitory activity that increased with increased dose (1-5 mg/mL) from 60% to 100% inhibition. There was limited amount of -amylase inhibitory activity that reached a maximum of 40% inhibition at 5 mg/mL treatment. Significant ACE inhibitory activity was detected for CP-SAB at 100 and 200 mg/mL sample concentrations. These in vitro results indicate the potential of cranberry powders as dietary supplement and food-based strategies for potential hyperglycemia management. This biochemical rationale provides the basis for further design of animal and clinical studies using standardized extracts.

A randomised trial of cranberry versus apple juice in the management of urinary symptoms during external beam radiation therapy for prostate cancer

Posted: November 13, 2010
Authors: Campbell G, Pickles T, D'yachkova Y
Journal: Clin Oncol (R Coll Radiol) 15(6):322-8

Abstract: AIMS: The aim of the study was to assess whether the oral intake of cranberry juice cocktail compared with apple juice was associated with a significant difference in urinary symptoms experienced during radical external beam radiation therapy (EBRT) for prostate carcinoma. MATERIALS AND METHODS: One hundred and twelve men with prostate cancer were randomised to either 354 ml cranberry juice or apple juice a day. Stratification was based on a history of a previous transurethral resection of prostate (TURP yes/no) and baseline International Prostate Symptom Score (IPSS < 6 or > or = 6) of urinary symptoms. RESULTS: The maximum IPSS (MRT) and the maximum change in IPSS from baseline (DRT) are used to report the results. We analysed the effects of juice allocation on DRT and MRT using analysis of covariates (ANCOVA). We observed no significant difference for DRT (P = 0.39) or MRT (P = 0.76) related to the consumption of cranberry compared with apple juice. However, we found a significant relationship between the history of a previous TURP and both DRT (P = 0.01) and MRT (P = 0.01). The history of a previous TURP was associated with lower values for both end points. Baseline IPSS was significant for DRT (P = 0.004) and MRT (P < or = 0.001). We found a significant relationship between the baseline IPSS < 6 or > or = 6 cut point on MRT (P < or = 0.001) but not on DRT (P = 0.43). The use of neoadjuvant hormones had no significant effect on DRT (P = 0.64) or MRT (P = 0.76). The use of additional symptomatic medication during the study was not significantly different between the two arms. CONCLUSIONS: This study shows no significant difference in the urinary symptoms experienced during EBRT related to the consumption of cranberry juice compared with apple juice.

Anti-inflammatory activity of a high-molecular-weight cranberry fraction on macrophages stimulated by lipopolysaccharides from periodontopathogens

Posted: November 13, 2010
Authors: Bodet C, Chandad F, Grenier D
Journal: J Dent Res 85(3):235-9

Abstract: Periodontitis is a chronic inflammatory disease affecting oral tissues. The continuous, high production of cytokines by host cells triggered by periodontopathogens is thought to be responsible for the destruction of tooth-supporting tissues. Macrophages play a critical role in this host inflammatory response to periodontopathogens. The aim of this study was to investigate the effect of non-dialyzable material prepared from cranberry juice concentrate on the pro-inflammatory cytokine response of macrophages induced by lipopolysaccharides (LPS) from Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum subsp. nucleatum, Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, and Escherichia coli. Interleukin-1 beta (IL-1beta), IL-6, IL-8, tumor necrosis factor alpha (TNF-alpha), and Regulated on Activation Normal T-cell Expressed and Secreted (RANTES) production by macrophages treated with the cranberry fraction prior to stimulation by LPS was evaluated by ELISA. Our results clearly indicate that the cranberry fraction was a potent inhibitor of the pro-inflammatory cytokine and chemokine responses induced by LPS. This suggests that cranberry constituents may offer perspectives for the development of a new therapeutic approach to the prevention and treatment of periodontitis.

Cranberry extract inhibits low density lipoprotein oxidation

Posted: November 13, 2010
Authors: Wilson T, Porcari JP, Harbin D
Journal: Life Sci 62(24):A381-6

Abstract: Cranberry juice consumption is often used for the treatment of urinary tract infections, but the effect of cranberry juice on heart disease has not been investigated. We evaluated how a cranberry extract containing 1,548 mg gallic acid equivalents/liter (initial pH=2.50) affected low density lipoprotein (LDL) oxidation induced by 10 micromolar cupric sulfate. When LDL oxidation took place in the presence of diluted cranberry extracts, the formation of thiobarbituric acid reactive substances (TBARS) and LDL electrophoretic mobility were reduced. LDL electrophoretic migration was also reduced when the cranberry extract had a pH of 7.00 prior to dilution. This study suggests that cranberry extracts have the ability to inhibit the oxidative modification of LDL particles.

Cranberry juice and its impact on peri-stomal skin conditions for urostomy patients

Posted: November 13, 2010
Authors: Tsukada K, Tokunaga K, Iwama T, Mishima Y, Tazawa K, Fujimaki M.
Journal: Ostomy Wound Manage 40(9):60-2, 64, 66-8

Abstract: In urostomy patients, peristomal skin problems are common and may stem from alkaline urine. Cranberry juice appears to acidify urine and has bacteriostatic properties, and is widely recommended for the reduction of urinary tract infections. Therefore, it is hypothesized that drinking cranberry juice might also prevent and/or improve skin complications for urostomy patients. To test this hypothesis, pH measurements of the skin around the stoma and of the urine of 13 urostomy patients were taken before and after instituting a regimen of drinking 160 to 320 g of cranberry juice each day for an average period of six months. Results showed an improvement in skin condition from 6 patients with erythema, maceration or pseudoepithelial hyperplasia at the beginning of the study to 2 patients with maceration or PEH. The average pH of the urine taken from the patients' pouches decreased a statistically significant amount from 8.0 to 7.3 (p = 0.0277), yet unexpectantly, the average pH of the fresh urine increased a statistically significant amount from 5.8 to 6.2 (p = 0.0178). Other results were not statistically significant. The authors conclude that while drinking cranberry juice did not appear to acidify the urine as expected, improvements were still seen in the skin conditions of the study participants, suggesting that drinking cranberry juice does positively impact the incidence of skin complications for these patients.

Dietary supplementation with cranberry concentrate tablets may increase the risk of nephrolithiasis.

Posted: November 13, 2010
Authors: Terris MK, Issa MM, Tacker JR
Journal: Urology 57(1):26-9

Abstract: OBJECTIVES: Cranberry juice has been recommended for patients with recurrent urinary tract infections. However, cranberry juice has a moderately high concentration of oxalate, a common component of kidney stones, and should be limited in patients with a history of nephrolithiasis. Cranberry concentrate tablets are currently available at nutrition stores and are sold as promoters of urinary tract health. After one of our patients with a distant history of calcium oxalate nephrolithiasis developed recurrent stones following self-administration of cranberry concentrate tablets, we sought to investigate the potential lithogenic properties of cranberry supplements.

METHODS: Five healthy volunteers on a normal diet provided 24-hour urine collection for pH, volume, creatinine, oxalate, calcium, phosphate, uric acid, sodium, citrate, magnesium, and potassium. Cranberry tablets were administered to these volunteers at the manufacturer's recommended dosage for 7 days. On the seventh day, a second 24-hour urine collection was obtained.

RESULTS: The urinary oxalate levels in the volunteers significantly increased (P = 0.01) by an average of 43.4% while receiving cranberry tablets. The excretion of potential lithogenic ions calcium, phosphate, and sodium also increased. However, inhibitors of stone formation, magnesium and potassium, rose as well.

CONCLUSIONS: Cranberry concentrate tablets are marketed for urinary tract ailments. Physicians and manufacturers of cranberry products should make an effort to educate patients at risk for nephrolithiasis against ingestion of these dietary supplements.

Effect of cranberry juice consumption on urinary stone risk factors

Posted: November 13, 2010
Authors: Gettman MT, Ogan K, Brinkley LJ, Adams-Huet B, Pak CY, Pearle MS
Journal: J Urol 174(2):590-4

Abstract: PURPOSE: We evaluated the effect of cranberry juice on urinary stone risk factors.

MATERIALS AND METHODS: A total of 12 normal subjects and 12 calcium oxalate stone formers underwent 2, 7-day phases of study in random order while on a controlled metabolic diet. Subjects ingested 1 l of cranberry juice (CBJ) daily in 1 phase and 1 l of deionized water in the other phase. On the last 2 days of each phase 2, 24-hour urine collections and blood samples were obtained for stone risk factors and serum chemistries.

RESULTS: No significant differences were found between normal subjects and stone formers in response to CBJ and, therefore, the groups were combined. CBJ significantly increased urinary calcium (from 154 to 177 mg per day, p =0.0008) and urinary oxalate (from 26.4 to 29.2 mg per day, p =0.04), thereby increasing urinary saturation of calcium oxalate by 18%. Urinary citrate was unchanged and urinary magnesium increased slightly. Urinary pH decreased (from 5.97 to 5.67, p =0.0005), and urinary ammonium, titratable acidity and net acid excretion increased during CBJ ingestion. Urinary uric acid decreased (from 544 to 442 mg per day, p <0.0001) as did serum uric acid. Thus, the urinary saturation of brushite and monosodium urate was reduced by CBJ but the amount of undissociated uric acid increased.

CONCLUSIONS: CBJ exerts a mixed effect on urinary stone forming propensity. It reduces urinary pH likely by providing an acid load and decreases urinary uric acid perhaps by retarding urate synthesis. Overall CBJ increases the risk of calcium oxalate and uric acid stone formation but decreases the risk of brushite stones.

Effect of cranberry juice on bacteriuria in children with neurogenic bladder receiving intermittent catheterization

Posted: November 13, 2010
Authors: Schlager TA, Anderson S, Trudell J, Hendley JO
Journal: J Pediatr 135(6):698-702

Abstract: OBJECTIVE: To determine the effect of cranberry prophylaxis on rates of bacteriuria and symptomatic urinary tract infection in children with neurogenic bladder receiving clean intermittent catheterization.

DESIGN: Double-blind, placebo-controlled, crossover study of 15 children receiving cranberry concentrate or placebo concentrate for 6 months (3 months receiving one concentrate, followed by 3 months of the other). Weekly home visits were made. During each visit, a sample of bladder urine was obtained by intermittent catheterization. Signs and symptoms of urinary tract infection and all medications were recorded, and juice containers were counted.

RESULTS: During consumption of cranberry concentrate, the frequency of bacteriuria remained high. Cultures of 75% (114 of 151) of the 151 samples obtained during consumption of placebo were positive for a pathogen (>/=10(4) colony-forming units/mL) compared with 75% (120 of 160) of the 160 samples obtained during consumption of cranberry concentrate. Escherichia coli remained the most common pathogen during placebo and cranberry periods. Three symptomatic infections each occurred during the placebo and cranberry periods. No significant difference was observed in the acidification of urine in the placebo group versus the cranberry group (median, 5.5 and 6.0, respectively).

CONCLUSION: The frequency of bacteriuria in patients with neurogenic bladder receiving intermittent catheterization is 70%; cranberry concentrate had no effect on bacteriuria in this population.

Effect of hypochlorhydria due to omeprazole treatment or atrophic gastritis on protein-bound vitamin B12 absorption.

Posted: November 13, 2010
Authors: Saltzman JR, Kemp JA, Golner BB, Pedrosa MC, Dallal GE, Russell RM
Journal: J Am Coll Nutr 13(6):584-91

Abstract: OBJECTIVE: To investigate the effects of hypochlorhydria and acidic drink ingestion on protein-bound vitamin B12 absorption in elderly subjects.

METHODS: Absorption of protein-bound vitamin B12 was examined in elderly normal subjects (n = 8), and in hypochlorhydric subjects due to omeprazole treatment (n = 8) or with atrophic gastritis (n = 3). Subjects underwent absorption tests of protein-bound vitamin B12 ingested with water, cranberry juice and 0.1 N hydrochloric acid.

RESULTS: Protein-bound vitamin B12 absorption was lower in the omeprazole-treated group (0.50%) compared to the normal group (1.21%; p < 0.001). With cranberry juice ingestion, the omeprazole-treated group showed an increase in absorbed protein-bound vitamin B12 (p = 0.025). With dilute hydrochloric acid ingestion, there was a further increase in vitamin B12 absorption (p < 0.001).

CONCLUSION: Omeprazole causes protein-bound vitamin B12 malabsorption, and ingestion of an acidic drink improves protein-bound vitamin B12 absorption.

Effects of a high-molecular-weight cranberry fraction on growth, biofilm formation and adherence of Porphyromonas gingivalis

Posted: November 13, 2010
Authors: Labrecque J, Bodet C, Chandad F, Grenier D
Journal: J Antimicrob Chemother 58(2):439-43

Abstract: BACKGROUND: Porphyromonas gingivalis is a major aetiological agent of periodontitis, a destructive disease affecting the tooth-supporting tissues. Recent reports have indicated that high-molecular-weight molecules from cranberry juice concentrate can prevent the attachment of human pathogens to host tissues.

OBJECTIVES: The aim of the present study was to investigate the effect of non-dialysable material (NDM) prepared from cranberry juice concentrate on growth, biofilm formation and adherence properties of P. gingivalis.

METHODS: The effect of cranberry NDM on biofilm formation was studied using a polystyrene microplate assay and by scanning electron microscopy. The effect of cranberry NDM on the attachment properties of P. gingivalis was evaluated by a microplate assay in which mammalian proteins were immobilized into wells.

RESULTS: Our results indicated that cranberry NDM is a potent inhibitor of biofilm formation by P. gingivalis. However, it has no effect on growth and viability of bacteria. Cranberry NDM also prevented significantly the attachment of P. gingivalis to surfaces coated with type I collagen, fibrinogen or human serum.

CONCLUSIONS: Our data suggest that cranberry constituents may have a beneficial effect for the prevention and treatment of periodontitis by reducing the capacity of P. gingivalis to colonize periodontal sites.

Efficacy of cranberry juice and ascorbic acid in acidifying the urine in multiple sclerosis subjects

Posted: November 13, 2010
Authors: Schultz A
Journal: J Community Health Nurs 1(3):159-69

Abstract: No abstract - The purpose of this study was to investigate the efficacy of carnberry juice and ascorbic acid in acidifying the urine of subjects with multiple sclerosis.

Inhibiting interspecies coaggregation of plaque bacteria with a cranberry juice constituent

Posted: November 13, 2010
Authors: Weiss EI, Lev-Dor R, Kashamn Y, Goldhar J, Sharon N, Ofek I
Journal: J Am Dent Assoc 129(12):1719-23

Abstract: Dental plaque stability depends on bacterial adhesion to acquired pellicle, and on interspecies adhesion (or coaggregation). A high-molecular-weight cranberry constituent at 0.6 to 2.5 milligrams per milliliter reversed the coaggregation of 49 (58 percent) of 84 coaggregating bacterial pairs tested. It acted preferentially on pairs in which one or both members are gram-negative anaerobes frequently involved in periodontal diseases. Thus, the anticoaggregating cranberry constituent has the potential for altering the subgingival microbiota, resulting in conservative control of gingival and periodontal diseases. However, the high dextrose and fructose content of the commercially available cranberry juice makes it unsuitable for oral hygiene use, and the beneficial effect of the high-molecular-weight constituent requires animal and clinical studies.

Inhibition of Helicobacter pylori adhesion to human gastric mucus by a high-molecular-weight constituent of cranberry juice.

Posted: November 13, 2010
Authors: Burger O, Weiss E, Sharon N, Tabak M, Neeman I and Ofek I
Journal: Crit Rev Food Sci Nutr 42(3 Suppl):279-84

Abstract: A high-molecular-weight constituent of cranberry juice has been found to inhibit the sialyllactose specific adhesion of Helicobacter pylori strains to immobilized human mucus, erythrocytes, and cultured gastric epithelial cells. Different isolates of H. pylori differ in their affinity to the cranberry juice constituent. Cranberry juice may also inhibit adhesion of bacteria to the stomach in vivo, and may prove useful for the prevention of stomach ulcer that is caused by H. pylori.

Inhibition of host extracellular matrix destructive enzyme production and activity by a high-molecular-weight cranberry fraction

Posted: November 13, 2010
Authors: Bodet C, Chandad F, Grenier D
Journal: J Periodontal Res 42(2):159-68

Abstract: BACKGROUND AND OBJECTIVE: Periodontal diseases are a group of inflammatory disorders that are initiated by specific gram-negative bacteria and lead to connective tissue destruction. Proteolytic enzymes, including matrix metalloproteinases (MMPs) and elastase, produced by resident and inflammatory cells in response to periodontopathogens and their products, play a major role in gingival tissue destruction. The aim of this study was to investigate the effect of a high-molecular-weight fraction prepared from cranberry juice concentrate on MMP-3, MMP-9 and elastase activities, as well as on MMP production by human cells stimulated with lipopolysaccharide of Actinobacillus actinomycetemcomitans.

MATERIAL AND METHODS: MMP-3 and MMP-9 production by gingival fibroblasts and macrophages treated with the cranberry fraction and then stimulated with lipopolysaccharide was measured by enzyme-linked immunosorbent assay. MMP-3, MMP-9 and elastase activities in the presence of the cranberry fraction were evaluated using colorimetric or fluorogenic substrates. The changes in expression and phosphorylation state of fibroblast intracellular signaling proteins induced by A. actinomycetemcomitans lipopolysaccharide and the cranberry fraction were characterized by antibody microarrays.

RESULTS: The lipopolysaccharide-induced MMP-3 and MMP-9 responses of fibroblasts and macrophages were inhibited in a dose-dependent manner by the cranberry fraction. This fraction was found to inhibit fibroblast intracellular signaling proteins, a phenomenon that may lead to a down-regulation of activating protein-1 activity. MMP-3, MMP-9 and elastase activities were also efficiently inhibited by the cranberry fraction, even when it was used at low concentrations.

CONCLUSION: These results suggest that cranberry compounds offer promising perspectives for the development of novel host-modulating strategies for an adjunctive treatment of periodontitis.

Inhibition of periodontopathogen-derived proteolytic enzymes by a high-molecular-weight fraction isolated from cranberry

Posted: November 13, 2010
Authors: Bodet C, Piché M, Chandad F, Grenier D
Journal: J Antimicrob Chemother 57(4):685-90

Abstract: BACKGROUND: Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola are three major aetiological agents of chronic periodontitis. The strong proteolytic activities of these bacteria are critical to their survival since their energy source is obtained from peptides and amino acids derived from proteins. In addition, proteases are important factors contributing to periodontal tissue destruction by a variety of mechanisms, including direct tissue degradation and modulation of host inflammatory responses.

OBJECTIVES: The aim of this study was to investigate the effect of non-dialysable material (NDM) prepared from cranberry juice concentrate on the proteolytic activities of P. gingivalis, T. forsythia and T. denticola.

METHODS: The effect of NDM on gingipain and dipeptidyl peptidase IV (DPP IV) activities of P. gingivalis, trypsin-like activity of T. forsythia and chymotrypsin-like activity of T. denticola was evaluated using synthetic chromogenic peptides. In addition, the capacity of P. gingivalis to degrade fluorescein-labelled type I collagen and fluorescein-labelled transferrin in the presence of NDM was evaluated by fluorometry.

RESULTS: NDM dose-dependently inhibited the proteinases of P. gingivalis, T. forsythia and T. denticola as well as type I collagen and transferrin degradation by P. gingivalis.

CONCLUSIONS: These results suggest that NDM has the potential to reduce either the proliferation of P. gingivalis, T. forsythia and T. denticola in periodontal pockets or their proteinase-mediated destructive process occurring in periodontitis.

Inhibitory activity of cranberry juice on adherence of type 1 and type P fimbriated Escherichia coli to eucaryotic cells

Posted: November 13, 2010
Authors: Zafriri D, Ofek I, Adar R, Pocino M, Sharon N

Abstract: Inhibition of bacterial adherence to bladder cells has been assumed to account for the beneficial action ascribed to cranberry juice and cranberry juice cocktail in the prevention of urinary tract infections (A. E. Sobota, J. Urol. 131:1013-1016, 1984). We have examined the effect of the cocktail and juice on the adherence of Escherichia coli expressing surface lectins of defined sugar specificity to yeasts, tissue culture cells, erythrocytes, and mouse peritoneal macrophages. Cranberry juice cocktail inhibited the adherence of urinary isolates expressing type 1 fimbriae (mannose specific) and P fimbriae [specific for alpha-D-Gal(1----4)-beta-D-Gal] but had no effect on a diarrheal isolate expressing a CFA/I adhesin. The cocktail also inhibited yeast agglutination by purified type 1 fimbriae. The inhibitory activity for type 1 fimbriated E. coli was dialyzable and could be ascribed to the fructose present in the cocktail; this sugar was about 1/10 as active as methyl alpha-D-mannoside in inhibiting the adherence of type 1 fimbriated bacteria. The inhibitory activity for the P fimbriated bacteria was nondialyzable and was detected only after preincubation of the bacteria with the cocktail. Cranberry juice, orange juice, and pineapple juice also inhibited adherence of type 1 fimbriated E. coli, most likely because of their fructose content. However, the two latter juices did not inhibit the P fimbriated bacteria. We conclude that cranberry juice contains at least two inhibitors of lectin-mediated adherence of uropathogens to eucaryotic cells. Further studies are required to establish whether these inhibitors play a role in vivo.

Interaction between warfarin and cranberry juice

Posted: November 13, 2010
Authors: Aston JL, Lodolce AE, Shapiro NL
Journal: Pharmacotherapy 26(9):1314-9

Abstract: Warfarin is extensively used for anticoagulation to a target international normalized ratio of 2.0-3.0 for most indications or 2.5-3.5 for high-risk indications; however, many drugs and dietary supplements induce fluctuations in the international normalized ratio. Such fluctuations may lead to therapeutic failure or bleeding complications. Cranberry juice is increasingly used for the prevention and adjunctive treatment of urinary tract infections. The United Kingdom's Committee on Safety of Medicines has alerted clinicians to a potential interaction between warfarin and cranberry juice and has advised that patients avoid their concurrent use. Review and analysis of the literature revealed that ingestion of large volumes of cranberry juice destabilize warfarin therapy. Small amounts of juice are not expected to cause such an interaction. Clinicians should be aware of this potential interaction and monitor and counsel patients accordingly.

Potential of cranberry-based herbal synergies for diabetes and hypertension management

Posted: November 13, 2010
Authors: Apostolidis E, Kwon YI, Shetty K
Journal: Asia Pac J Clin Nutr 15(3):433-41

Abstract: Water soluble cranberry-based phytochemical combinations with oregano, rosemary, and Rhodiola rosea were evaluated for total phenolic content, related antioxidant activity and inhibition of diabetes management-related alpha -glucosidase, pancreatic alpha-amylase inhibition, and hypertension-related ACE-I inhibitory activities. Water extracts of oregano had 114.9 mg/g DW of phenolics which was highest among all the extracts tested, whereas the 75% cranberry with 25% oregano combinations had the highest phenolics (38.9 mg/g DW) among all the combinations tested. The water extracts of oregano had the highest DPPH radical inhibition activity (73.6 %), whereas among combinations the 75% cranberry and 25% oregano had the highest DPPH radical inhibition activity (50.8 %). These results indicated a correlation between total phenolic content and antioxidant activity. The water extracts of pure Rhodiola rosea had the highest alpha -glucosidase inhibition, whereas the 75% cranberry and 25% Rhodiola rosea combination had the highest inhibition among the combinations. In the case of alpha -amylase inhibition the water extracts of Rhodiola rosea had the highest inhibition, whereas the 75% cranberry with 25% Rhodiola rosea combination had the highest inhibition among the combinations. All the water extracts tested indicated that they had anti-ACE-I inhibitory activity. More specifically, among the water extracts 100% cranberry had the highest ACE-I inhibitory activity and among the combination the 75% cranberry with 25% rosemary had the highest ACE-I inhibitory activity. The analysis of alpha -glucosidase,alpha -amylase, and ACE-I inhibitory activities suggested that inhibition depend on the phenolic profile of each unique extract and by bringing together synergistic combinations to cranberry, health beneficial functionality was enhanced. This enhanced functionality in terms of high alpha -glucosidase and alpha -amylase inhibitory activities indicate the potential for diabetes management, and high ACE-I inhibitory activity indicates the potential for hypertension management.

Recurrent cystitis in non-pregnant women

Posted: November 13, 2010
Authors: Sen A
Journal: Clin Evid 07:801

Abstract: INTRODUCTION: Cystitis is a bacterial infection of the lower urinary tract which causes pain when passing urine, and causes urgency, haematuria, and suprapubic pain not associated with passing urine. Recurrent cystitis is usually defined as three episodes of urinary tract infection in the previous 12 months, or two episodes in the previous 6 months. METHODS AND

OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: Which interventions prevent further recurrence of cystitis in women experiencing at least two infections per year? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

RESULTS: We found 14 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: continuous antibiotic prophylaxis (trimethoprim, co-trimoxazole, nitrofurantoin, cefaclor, or a quinolone or cephalexin); continuous prophylaxis with methenamine hippurate; cranberry juice and cranberry products; oestrogen (topical) in postmenopausal women; passing urine after intercourse; postcoital antibiotic prophylaxis; single-dose self-administered antibiotic.

The effectiveness of dried cranberries ( Vaccinium macrocarpon) in men with lower urinary tract symptoms

Posted: November 13, 2010
Authors: Vidlar A, Vostalova J, Ulrichova J, Student V, Stejskal D, Reichenbach R, Vrbkova J, Ruzicka F, Simanek V.
Journal: Br J Nutr 104(8):1181-9

Abstract: Lower urinary tract symptoms (LUTS) are a common condition in older men. The objective of the present study was to evaluate the efficacy and tolerability of cranberry (Vaccinium macrocarpon) powder in men at risk of prostate disease with LUTS, elevated prostate-specific antigen (PSA), negative prostate biopsy and clinically confirmed chronic non-bacterial prostatitis. Forty-two participants received either 1500 mg of the dried powdered cranberries per d for 6 months (cranberry group; n 21) or no cranberry treatment (control group; n 21). Physical examination, International Prostate Symptom Score, quality of life (QoL), five-item version of the International Index of Erectile Function (IIEF-5), basic clinical chemistry parameters, haematology, Se, testosterone, PSA (free and total), C-reactive protein (CRP), antioxidant status, transrectal ultrasound prostate volume, urinary flow rate, ultrasound-estimated post-void residual urine volume at baseline, and at 3 and 6 months, and urine ex vivo anti-adherence activity were determined in all subjects. In contrast to the control group, patients in the cranberry group had statistically significant improvement in International Prostate Symptom Score, QoL, urination parameters including voiding parameters (rate of urine flow, average flow, total volume and post-void residual urine volume), and lower total PSA level on day 180 of the study. There was no influence on blood testosterone or serum CRP levels. There was no statistically significant improvement in the control group. The results of the present trial are the first firm evidence that cranberries may ameliorate LUTS, independent of benign prostatic hyperplasia or C-reactive protein level.

Effect of blackcurrant-, cranberry- and plum juice consumption on risk factors associated with kidney stone formation.

Posted: November 11, 2010
Authors: Kessler T, Jansen B, Hesse A
Journal: Eur J Clin Nutr 56:1020-3

Abstract: OBJECTIVE: To evaluate the influence of plum-, cranberry- and blackcurrant juice on urinary stone risk factors.

DESIGN: Investigations were carried out in 12 healthy male subjects aged 18-38 y. All subjects received a standardized diet formulated according to the dietary recommendations of the German Society of Nutrition. The subjects provided 24 h urine collections in a control, three loading phases. In each loading phase a neutral mineral water was substituted for 330 ml of the particular juice.

RESULTS: Cranberry juice decreased the urinary pH, whereas the excretion of oxalic acid and the relative supersaturation for uric acid were increased. Blackcurrant juice increased the urinary pH and the excretion of citric acid. The excretion of oxalic acid was increased too. All changes were statistically significant. The plum juice had no significant effect on the urinary composition.

CONCLUSION: It is concluded that blackcurrant juice could support the treatment and metaphylaxis of uric acid stone disease because of its alkalizing effect. Since cranberry juice acidifies urine it could be useful in the treatment of brushite and struvite stones as well as urinary tract infection.

Pomelo juice, but not cranberry juice, affects the pharmacokinetics of cyclosporine in humans

Posted: November 11, 2010
Authors: Grenier J, Fradette C, Morelli G, Merritt GJ, Vranderick M, Ducharme MP
Journal: Clin Pharmacol Ther 79(3):255-62

Abstract: BACKGROUND: Cyclosporine (INN, ciclosporin) is a cytochrome P450 (CYP) 3A and P-glycoprotein (P-gp) substrate whose bioavailability increases when administered with grapefruit juice. It is unknown whether pomelo, a closely related citrus fruit, interacts with cyclosporine in humans. In addition, a case study reports that cranberry juice interacts with warfarin, a drug with a narrow therapeutic range. Cranberries have a high content of flavonoids, compounds with various metabolic effects, including interaction with P-gp in vitro. Although the effect of flavonoids is less evident in vivo, cranberry juice has become a very popular beverage, and it was deemed important to investigate whether it has an effect on the disposition of cyclosporine, another drug with a narrow therapeutic range.

METHODS: In an open-label, randomized, 3-way crossover study with a 14-day washout period between each dose, 12 healthy male volunteers received single oral 200-mg doses of cyclosporine according to the following regimens: 200 mg cyclosporine administered with 240 mL of pomelo juice, cranberry juice, or water under fasting conditions. Multiple whole blood samples were collected up to 36 hours after each dose. Concentrations were determined via a liquid chromatography-tandem mass spectrometry method.

RESULTS: Administration of pomelo juice with cyclosporine increased the area under the curve from time 0 to the last measurable concentration (AUCt), area under the curve from time 0 to infinity (AUCinf), and maximum blood concentration (Cmax) of cyclosporine with ratios of least squares means of 119.4% (95% confidence interval [CI], 113.4%-125.8%), 118.9% (95% CI, 113.8%-124.3%), and 112.1% (95% CI, 102.3%-122.8%), respectively. All 3 variables exhibited statistically significant increases (with Bonferroni adjustment), with P = .0001 for AUCt and AUCinf and P = .0167 for Cmax; however, only the increase in AUCt was judged to be clinically significant with a 95% CI outside the 80% to 125% boundaries. Cranberry juice had no clinically significant effect on the overall disposition of cyclosporine. After administration of cyclosporine with cranberry juice, the ratios of least squares means for AUCt, AUCinf, and Cmax for cyclosporine were 95.0% (95% CI, 90.3%-100.1%), 93.4% (95% CI, 89.2%-97.8%), and 95.2% (95% CI, 86.9%-104.2%), respectively.

CONCLUSION: These results suggest that pomelo juice increases the bioavailability of cyclosporine, possibly by inhibiting CYP3A or P-gp activity (or both) in the gut wall. However, drinking a glass of cranberry juice does not appear to significantly influence the disposition of cyclosporine.

A-type cranberry proanthocyanidins and uropathogenic bacterial anti-adhesion activity

Posted: November 10, 2010
Authors: Howell AB, Reed JD, Krueger CG, Winterbottom R, Cunningham DG, Leahy M
Journal: Phytochemistry 66(18):2281-91

Abstract: Clinical, epidemiological and mechanistic studies support the role of cranberry (Vaccinium macrocarpon Ait.) in maintaining urinary tract health. Cranberry proanthocyanidins contain A-type linkages and have been associated with preventing adhesion of P-fimbriated uropathogenic Escherichia coli to uroepithelial cells. It is not known if the presence of the A-type linkage is a prerequisite for anti-adhesion activity. Other commercial sources of proanthocyanidins with all B-type linkages have not previously been screened for this activity. The goals of this study were to compare the in vitro anti-adhesion activity of A-linked proanthocyanidins from cranberry juice cocktail with the anti-adhesion activities of B-linked proanthocyanidins from commercial grape and apple juices, green tea and dark chocolate, and determine if anti-adhesion activity is detectable in human urine following consumption of single servings of each commercial food product. Structural heterogeneity and presence of the A-type linkage in cranberry proanthocyanidins was confirmed utilizing MALDI-TOF/MS and DI/ESI MS, as was the presence of all B-type linkages in the proanthocyanidins from the other commercial products. The isolated A-type proanthocyanidins from cranberry juice cocktail elicited in vitro anti-adhesion activity at 60 microg/ml, the B-type proanthocyanidins from grape exhibited minor activity at 1200 microg/ml, while other B-type proanthocyanidins were not active. Anti-adhesion activity in human urine was detected following cranberry juice cocktail consumption, but not after consumption of the non-cranberry food products. Results suggest that presence of the A-type linkage in cranberry proanthocyanidins may enhance both in vitro and urinary bacterial anti-adhesion activities and aid in maintaining urinary tract health.

Cranberry juice and urinary tract infections: what is the evidence?

Posted: November 10, 2010
Authors: Lowe FC, Fagelman E
Journal: Urology 57(3):407-13

Abstract: No abstract - Introduction: It is well “known” by the general lay public that cranberry juice is helpful in treating and preventing urinary tract infections (UTIs). However, the evidence for this assumption has never been critically reviewed in urologic reports or elsewhere. The evidence for the two proposed mechanisms of action of cranberry juice, urinary acidification and inhibition of bacterial adherence, are critically analyzed.

Cranberry juice for the prevention of recurrent urinary tract infections: a randomized controlled trial in children

Posted: November 10, 2010
Authors: Ferrara P, Romaniello L, Vitelli O, Gatto A, Serva M and Cataldi L
Journal: Scand J Urol Nephrol 43(5):369-72

Abstract: OBJECTIVE: This study compares the effects of daily cranberry juice to those of Lactobacillus in children with recurrent urinary tract infections (UTIs).

MATERIAL AND METHODS: Eighty-four girls aged between 3 and 14 years were randomized to cranberry, Lactobacillus or control in three treatment arms: G1, cranberry juice 50 ml daily (n=28); G2, 100 ml of Lactobacillus GG drink on 5 days a month (n=27); and G3, controls (n=29). The study lasted for 6 months.

RESULTS: Only four subjects withdrew: 1/28 (3.5%) from G1, 1/27 (3.7%) from G2 and 2/29 (6.8%) from G3, because of poor compliance to the established protocol. There were 34 episodes of UTIs in this cohort: 5/27 (18.5%) in G1, 11/26 (42.3%) in G2 and 18/27 (48.1%) in the G3, with at least one episode of infection (p<0.05).

CONCLUSION: These data suggest that daily consumption of concentrated cranberry juice can significantly prevent the recurrence of symptomatic UTIs in children.

Cranberry products inhibit adherence of p-fimbriated Escherichia coli to primary cultured bladder and vaginal epithelial cells.

Posted: November 10, 2010
Authors: Gupta K, Chou MY, Howell A, Wobbe C, Grady R, Stapleton AE
Journal: J Urol 177(6):2357-60

Abstract: PURPOSE: Cranberry proanthocyanidins have been identified as possible inhibitors of Escherichia coli adherence to uroepithelial cells. However, little is known about the dose range of this effect. Furthermore, it has not been studied directly in the urogenital system. To address these issues we tested the effect of a cranberry powder and proanthocyanidin extract on adherence of a P-fimbriated uropathogenic E. coli isolate to 2 new urogenital model systems, namely primary cultured bladder epithelial cells and vaginal epithelial cells.

MATERIALS AND METHODS: E. coli IA2 was pre-incubated with a commercially available cranberry powder (9 mg proanthocyanidin per gm) or with increasing concentrations of proanthocyanidin extract. Adherence of E. coli IA2 to primary cultured bladder epithelial cells or vaginal epithelial cells was measured before and after exposure to these products.

RESULTS: Cranberry powder decreased mean adherence of E. coli IA2 to vaginal epithelial cells from 18.6 to 1.8 bacteria per cell (p <0.001). Mean adherence of E. coli to primary cultured bladder epithelial cells was decreased by exposure to 50 mug/ml proanthocyanidin extract from 6.9 to 1.6 bacteria per cell (p <0.001). Inhibition of adherence of E. coli by proanthocyanidin extract occurred in linear, dose dependent fashion over a proanthocyanidin concentration range of 75 to 5 mug/ml.

CONCLUSIONS: Cranberry products can inhibit E. coli adherence to biologically relevant model systems of primary cultured bladder and vaginal epithelial cells. This effect occurs in a dose dependent relationship. These findings provide further mechanistic evidence and biological plausibility for the role of cranberry products for preventing urinary tract infection.

Daily cranberry juice for the prevention of asymptomatic bacteriuria in pregnancy: a randomized, controlled pilot study

Posted: November 10, 2010
Authors: Wing DA, Rumney PJ, Preslicka C, Chung JH
Journal: J Urol 27(2):137-42

Abstract: PURPOSE: We compared the effects of daily cranberry juice cocktail to those of placebo during pregnancy on asymptomatic bacteriuria and symptomatic urinary tract infections.MATERIALS AND METHODS: A total of 188 women were randomized to cranberry or placebo in 3 treatment arms of A-cranberry 3 times daily (58), B-cranberry at breakfast then placebo at lunch and dinner (67), and C-placebo 3 times daily (63). After 27.7% (52 of 188) of the subjects were enrolled in the study the dosing regimens were changed to twice daily dosing to improve compliance.RESULTS: There were 27 urinary tract infections in 18 subjects in this cohort, with 6 in 4 group A subjects, 10 in 7 group B subjects and 11 in 7 group C subjects (p = 0.71). There was a 57% and 41% reduction in the frequency of asymptomatic bacteriuria and all urinary tract infections, respectively, in the multiple daily dosing group. However, this study was not sufficiently powered at the alpha 0.05 level (CI 0.14-1.39 and 0.22-1.60, respectively, incidence rate ratios). Of 188 subjects 73 (38.8%) withdrew, most for gastrointestinal upset.CONCLUSIONS: These data suggest there may be a protective effect of cranberry ingestion against asymptomatic bacteriuria and symptomatic urinary tract infections in pregnancy. Further studies are planned to evaluate this effect.

Does drinking cranberry juice produce urine inhibitory to the development of crystalline, catheter-blocking Proteus mirabilis biofilms?.

Posted: November 10, 2010
Authors: Morris NS, Stickler DJ
Journal: BJU Int 88(3):192-7

Abstract: OBJECTIVE: To test the recommendation that to avoid the complications of long-term indwelling bladder catheterization (e.g. encrustation and blockage by crystalline Proteus mirabilis biofilms) patients should drink cranberry juice. MATERIALS AND METHODS: Urine was collected from groups of volunteers who had drunk up to 2 x 500 mL of cranberry juice or water within an 8-h period. Laboratory models of the catheterized bladder were supplied with urine from these groups and inoculated with P. mirabilis. After incubation for 24 or 48 h, the extent of catheter encrustation was determined by chemical analysis for calcium and magnesium. Encrustation was also visualized by scanning electron microscopy. RESULTS: The amounts of calcium and magnesium recovered from catheters incubated in urine pooled from individuals who had drunk 500 mL of cranberry juice was not significantly different from that on catheters incubated in pooled urine from control subjects who had drunk 500 mL of water. However, there was significantly less encrustation (P = 0.007) on catheters from models receiving urine from volunteers who had drunk 2 x 500 mL of water than on catheters incubated in models supplied with urine from volunteers who had drunk 2 x 500 mL of cranberry juice. The amounts of encrustation on these two groups of catheters were also significantly less than that on catheters incubated in models supplied with urine from volunteers who had not supplemented their normal fluid intake. (P < 0.001). Experiments in the models using artificial urine showed that increasing the low fluid intake (720 mL/24 h) characteristic of many patients undergoing long-term catheterization by factors of three and six, significantly (P < 0.01) reduced the amounts of calcium and magnesium that formed on catheters. At a simulated fluid intake of 720 mL/24 h, catheters blocked with encrustation after a mean of 42.5 h, while those supplied with urine produced from an intake of 4320 mL/24 h, drained freely for > 10 days. CONCLUSION: In this in vitro study, drinking cranberry juice did not produce urine that was inhibitory to the development of crystalline catheter-blocking P. mirabilis biofilms. The important factor in preventing catheter encrustation is a high fluid intake.

Effect of cranberry drink on bacterial adhesion in vitro and vaginal microbiota in healthy females

Posted: November 10, 2010
Authors: Jass J and Reid G
Journal: Can J Urol 16(6):4901-7

Abstract: INTRODUCTION/OBJECTIVE: Cranberries have been shown to produce urinary metabolites that influence uropathogen adhesion and prevent urinary tract infections. This study was designed to determine if consuming reconstituted, unsweetened cranberry drink from extract retained its bioactive properties by reducing uropathogen adhesion without adversely affecting urinary calcium, magnesium and the vaginal microflora. MATERIALS AND METHODS: A randomized crossover study was undertaken in 12 healthy women consuming reconstituted unsweetened cranberry drink, CranActin or water. The urine was collected at 4 hours and 1 week of consumption and evaluated for antiadhesive properties and urinary pH, calcium and magnesium. Vaginal swabs were collected after 1 week of treatment to assess the vaginal microbiota by DGGE. RESULTS: The resultant urine produced by subjects who consumed 500 ml reconstituted cranberry extract twice per day, significantly reduced the adherence to epithelial cells of P-fimbriated uropathogenic Escherichia coli and showed a tendency towards significance for two E. coli strains expressing fimbriae and an Enterococcus faecalis isolate. The cranberry drink treatment did not alter urinary pH, but reduced calcium and magnesium concentrations compared to water, although not to statistical significance. The reconstituted cranberry drink had no apparent detrimental effect on the vaginal microbiota. However, consuming twice daily resulted in an apparent loss of a potential pathogen from the vagina in 42% subjects. CONCLUSIONS: The present findings suggest that reconstituted cranberry drink may retain the ability to reduce the risk of UTI by inhibiting pathogen adhesion while not detrimentally affecting urinary pH or vaginal microbiota, or the risk of calculi

Effect of cranberry juice on eradication of Helicobacter pylori in patients treated with antibiotics and a proton pump inhibitor.

Posted: November 10, 2010
Authors: Shmuely H, Yahav J, Samra Z, Chodick G, Koren R, Niv Y, Ofek I
Journal: Mol Nutr Food Res 51(6):746-51

Abstract: Cranberry constituents are known to exert anti-adhesion activity on H. pylori in vitro. To determine their possible additive effect to triple therapy with omeprazole, amoxicillin and clarithromycin (OAC), a double-blind randomized clinical study was carried out. One-hundred-seventy-seven patients with H. pylori infection treated with OAC for 1 week were randomly allocated to receive 250 mL of either cranberry juice (cranberry-OAC, n = 89) or placebo beverage (placebo-OAC, n = 88) twice daily and only cranberry juice or placebo beverage for the next 2 weeks. Treatment outcome was determined with the(13)C urea breath test ((13)C-UBT). An additional control group consisted of patients referred to the same center during the same period who were treated with OAC alone for 1 week (non-placebo-OAC, n = 712). Overall, the rate of H. pylori eradication ((13)C-UBT < 3.5) was 82.5%, with no statistically significant difference among the three arms. Analysis by gender revealed that for female subjects, the eradication rate was higher in the cranberry-OAC arm (n = 42, 95.2%) than in the placebo-OAC arm (n = 53, 86.8%) and significantly higher than in the non-placebo-OAC group (n = 425, 80%; p = 0.03). For males, the rate was nonsignificantly lower in the cranberry-OAC arm (n = 35, 73.9%) than in the placebo-OAC arm (n = 45, 80.0%) and non-placebo-OAC group (n = 287, 85.0%). These results suggest that the addition of cranberry to triple therapy improves the rate of H. pylori eradication in females.

Effect of feeding tube properties and three irrigants on clogging rates.

Posted: November 10, 2010
Authors: Metheny N, Eisenberg P and McSweeney M
Journal: Nurs Res 37(3):165-9

Abstract: An experimental study was conducted on 3 consecutive 12-hour days to determine if selected physical properties of feeding tubes (material and diameter) affect tube clogging. Effectiveness of three irrigant fluids (cranberry juice, Coca-Cola, and water) in preventing tube clogging was studied. One hundred eight tubes were connected to gravity flow feeding bags containing isotonic enteral formula; 54 polyurethane and 54 silicone tubes were equally divided as to external diameters of 8 French (Fr), 10 Fr, and 12 Fr. At 4-hour intervals, flow regulators on the feeding bags were adjusted to a rate of 50 ml/hour. Fluid volumes delivered per minute were measured for each tube at 2-hour intervals. One set of tubes at each station was irrigated periodically with cranberry juice, Coca-Cola, or water. On each of the 3 days, analyses revealed significant, p less than .05, effects for tube material, cranberry juice contrasted with Coca-Cola and water as irrigants, and time. Polyurethane was consistently superior to silicone as a tube material, and cranberry juice was consistently inferior to both Coca-Cola and water as an irrigant. Tube diameter had no significant effect on the incidence of tube clogging.

Effects of cranberry juice on uropathogenic Escherichia coli in vitro biofilm formation

Posted: November 10, 2010
Authors: Di Martino P, Agniel R, Gaillard JL, Denys P
Journal: J Chemother 17(5):563-5

Abstract: No abstract

Efficacy of cranberry juice on Helicobacter pylori infection: a double-blind, randomized placebo-controlled trial

Posted: November 10, 2010
Authors: Zhang L, Ma J, Pan K, Go VL, Chen J, You WC
Journal: Helicobacter 10(2):139-45

Abstract: BACKGROUND: Helicobacter pylori infection is a major cause of peptic ulcer disease and gastric cancer. This study postulated that cranberry juice would be effective in the suppression of H. pylori in an endemically infected population at high risk for gastric cancer.MATERIALS AND METHODS: A prospective, randomized, double-blind, placebo-controlled trial was conducted in Linqu County of Shandong Province, China, where 189 adults aged 48.9 +/- 11.2 years (mean +/- SD) with H. pylori infection were randomly divided into two groups: cranberry juice (n = 97) and placebo (n = 92). Participants were assigned to orally receive two 250-ml juice boxes of cranberry juice or matching placebo beverage daily for 90 days. The degree of H. pylori infection was determined using the 13C-urea breath test before randomization at 35 and 90 days of intervention to assess the efficacy of cranberry juice in alleviating infection.RESULTS: A total of 189 subjects with positive 13C-urea breath test results prior to randomization completed the study. At day 35 of intervention, 14 of the 97 (14.43%) from the the cranberry juice treatment group and 5 of the 92 (5.44%) of the placebo recipients had negative 13C-urea breath test results. After 90 days, the study concluded that 14 of the 97 subjects in the cranberry juice treatment group versus 5 of the 92 in the placebo group yielded negative test results. Eleven individuals from the cranberry juice treatment group and only two from the placebo group were negative at 35 and 90 days of experiment. These results are significant (p < .05).CONCLUSIONS: Regular consumption of cranberry juice can suppress H. pylori infection in endemically afflicted populations.

Fruit extracts antagonize A beta or DA-induced deficits in Ca2+ flux in M1-transfected COS-7 cells

Posted: November 10, 2010
Authors: Joseph JA, Fisher DR, Carey AN
Journal: JAD 6(4):403-411

Abstract: Evidence suggests that there is a selective sensitivity to oxidative stress (OSS) among muscarinic receptor (MAChR) subtypes with M1, M2 and M4 showing > OSS than M3 or M5 subtypes in transfected COS-7 cells. This may be important in determining the regional specificity in neuronal aging and Alzheimer disease (AD). We assessed the effectiveness of blueberry (BB) and other high antioxidant (HA) fruit extracts (boysenberry, BY; cranberry, CB; black currant, BC; strawberry, SB; dried plums, DP; and grape, GR) on the toxic effects of Abeta 25-35 (100 microM, 24 hrs) and DA (1 mM, 4 hrs) on calcium buffering (Recovery) following oxotremorine (750 microM) -induced depolarization in M1AChR-transfected COS-7 cells, and on cell viability following DA (4 hrs) exposure. The extracts showed differential levels of Recovery protection in comparisons to the non-supplemented controls that was dependent upon whether DA or Abeta was used as the pretreatment. Interestingly, assessments of DA-induced decrements in viability revealed that all of the extracts had some protective effects. These findings suggest that the putative toxic effects of Abeta or DA might be reduced by HA fruit extracts.

In vivo inhibition of growth of human tumor lines by flavonoid fractions from cranberry extract.

Posted: November 10, 2010
Authors: Ferguson PJ, Kurowska EM, Freeman DJ, Chambers AF and Koropatnick J
Journal: Nutr Cancer 56(1):86-94

Abstract: Edible fruits and berries may serve as sources for novel anticancer agents, given that extracts of these foods have demonstrated cytotoxic activity against tumor cell lines. Semipurified, flavonoid-rich extracts of cranberry (Vaccinia macrocarpa) were shown previously to arrest proliferation of tumor cells and induce apoptosis. However, the ability of cranberry flavonoids to inhibit tumor growth in vivo has not been reported other than in a preliminary report. As model systems for testing this activity, human tumor cell lines representative of three malignancies were chosen: glioblastoma multiforme (U87), colon carcinoma (HT-29), and androgen-independent prostate carcinoma (DU145). A flavonoid-rich fraction 6 (Fr6) and a more purified proanthocyanidin (PAC)-rich fraction were isolated from cranberry presscake and whole cranberry, respectively, by column chromatography. Fr6 and PAC each significantly slowed the growth of explant tumors of U87 in vivo, and PAC inhibited growth of HT-29 and DU145 explants (P < 0.05), inducing complete regression of two DU145 tumor explants. Flow cytometric analyses of in vitro-treated U87 cells indicated that Fr6 and PAC could arrest cells in G1 phase of the cell cycle (P < 0.05) and also induce cell death within 24 to 48 h of exposure (P < 0.05). These results indicate the presence of a potential anticancer constituent in the flavonoid-containing fractions from cranberry extracts.

Influence of cranberry phenolics on glucan synthesis by glucosyltransferases and Streptococcus mutans acidogenicity

Posted: November 10, 2010
Authors: Gregoire S, Singh AP, Vorsa N, Koo H
Journal: J Appl Microbiol 103(5):1960-8

Abstract: "AIMS: To investigate the influence of several phenolic compounds isolated from cranberry fruit (Vaccinium macrocarpon) on some of the virulence properties of Streptococcus mutans associated with glucan synthesis and acidogenicity.

METHODS AND RESULTS: Individual phenolic acids, flavonols and proanthocyanidins were isolated by semi-preparative high-performance liquid chromatography from fresh cranberry fruit. Flavonols and proanthocyanidins (at 500 micromol l(-1)) moderately inhibited the activity of surface-adsorbed glucosyltransferases (GTFs) B and C and F-ATPases (15-35% inhibition; P < 0.05), and also disrupted acid production by S. mutans cells without affecting bacterial viability. Phenolic acids displayed minimal biological effects. Quercetin-3-arabinofuranoside, myricetin and procyanidin A2 displayed the most inhibition of S. mutans virulence traits; a combination of these compounds displayed enhanced effects.

CONCLUSIONS: Specific flavonoids from cranberries exhibit statistically significant but moderate biological activity against S. mutans. The biological activity of cranberry extracts may be a result from the complex mixture of flavonoids rather than a single active compound.

SIGNIFICANCE AND IMPACT OF STUDY: This is the first study to identify the bioactive constituents in cranberry against an oral bacterium using highly purified isolated compounds. The combined effects of specific flavonols and proanthocyanidins from cranberry on GTFs activity, acid production and acid tolerance of S. mutans make them attractive compounds to fully explore for their anti-biofilm and cariostatic properties."

Inhibition of bacterial adherence by cranberry juice: potential use for the treatment of urinary tract infections

Posted: November 10, 2010
Authors: Sobota AE
Journal: J Urol 131(5):1013-6

Abstract: Cranberry juice has been widely used for the treatment and prevention of urinary tract infections and is reputed to give symptomatic relief from these infections. Attempts to account for the potential benefit derived from the juice have focused on urine acidification and bacteriostasis. In this investigation it is demonstrated that cranberry juice is a potent inhibitor of bacterial adherence. A total of 77 clinical isolates of Escherichia coli were tested. Cranberry juice inhibited adherence by 75 per cent or more in over 60 per cent of the clinical isolates. Cranberry cocktail was also given to mice in the place of their normal water supply for a period of 14 days. Urine collected from these mice inhibited adherence of E. coli to uroepithelial cells by approximately 80 per cent. Antiadherence activity could also be detected in human urine. Fifteen of 22 subjects showed significant antiadherence activity in the urine 1 to 3 hours after drinking 15 ounces of cranberry cocktail. It is concluded that the reported benefits derived from the use of cranberry juice may be related to its ability to inhibit bacterial adherence.

Inhibitory activity of cranberry extract on the bacterial adhesiveness in the urine of women: an ex-vivo study.

Posted: November 10, 2010
Authors: Tempera G, Corsello S, Genovese C, Caruso FE, Nicolosi D
Journal: Int J Immunopathol Pharmacol 23(2):611-8.

Abstract: Strains of uropathogenic E. coli are responsible for approximately 90% of community-acquired, uncomplicated cystitis, and fimbriae represent the adhesive factors enabling E. coli to be anchored to uroepithelial cells in the first step of the infectious process. Recently, a few studies have shown that a correlation between the consumption of cranberry (Vaccinium macrocarpon) and prevention of UTI is related to the ability of proanthocyanidins to reduce the bacterial adhesion to uroepithelial cells. In this study we evaluate the inhibitory activity of urine of healthy women treated with tablets containing cranberry extract on the adhesiveness of E. coli to uroepithelial human cells. Two groups of 12 female volunteers each, aged between 18 and 65 years, were enrolled, one group with negative history and one group with positive history of recurrent cystitis. Subjects were treated with the active product or placebo in a random, cross-over, double-blinded sequence for one week in each of the two treatment sequences. Urine samples were collected at the beginning and the end of each study period. Tests of bacterial adhesiveness were performed with two strains of E. coli (ATCC 25922 and ATCC 35218) on HT1376 human bladder carcinoma cells. Significant reductions of bacterial adhesiveness were observed in women who received cranberry extract (-50.9%; p less than 0.0001), regardless of their medical history and the treatment period in the cross-over sequence. No changes were observed with placebo (-0.29%; n.s.). This ex-vivo study showed that the assumption of cranberry extract in suitable amounts can have an anti-adhesive activity on uropathogenic E. coli.

Prevention of nonspecific bacterial cell adhesion in immunoassays by use of cranberry juice.

Posted: November 10, 2010
Authors: Johnson-White B, Buquo L, Zeinali M, Ligler FS
Journal: Anal Chem 78(3):853-7

Abstract: The ability of Vaccinum macrocarpon, the North American cranberry, to prevent bacterial adhesion has been used to advantage in the prevention of urinary tract infections and has recently been described for the prevention of adhesion of bacteria responsible for oral infections and stomach ulcers. This report documents the ability of cranberry juice to reduce nonspecific adhesion of bacteria to the borosilicate glass microscope slides used in an immunoarray biosensor format. Nonspecific binding of analytes in the array sensor leads to high background signals that cause increased detection limits and false positives. Reduction in background-to-signal ratios can be seen as the juice concentration is increased from 0 to 50% of the sample. This impact cannot be duplicated with grape, orange, apple, or white cranberry juice. Sugar content and pH have been eliminated as the agents in the juice responsible for the anti-adhesive activity.

Protective effects of cranberries on infection-induced oxidative renal damage in a rabbit model of vesico-ureteric reflux

Posted: November 10, 2010
Authors: Han CH, Kim SH, Kang SH, Shin OR, Lee HK, Kim HJ and Cho YH
Journal: BJU Int 100(5):1172-5

Abstract: OBJECTIVE: To evaluate the protective effects of cranberry fruit, which have known antioxidant effects, on infection-induced oxidative renal damage in a rabbit model of vesico-ureteric reflux (VUR). MATERIALS AND METHODS: In all, 36 New Zealand male rabbits were divided into five groups, with a sham operation in four rabbits serving as the control (group 1). To create unilateral VUR the roof of the left intravesical ureter was incised, and VUR confirmed 2 weeks after surgery. In all, 32 rabbits with VUR were divided into four groups; 2, VUR alone (with sterile urine); 3, a group infected with Escherichia coli; 4, with intravesical E. coli instillation but fed cranberries; and 5, intravesical E. coli instillation plus an intraperitoneal injection with melatonin group. At 3 weeks after surgery the rabbits were killed, the kidneys obtained and examined histopathologically to evaluate inflammation, fibrosis and tubular changes. Oxidative renal damage was evaluated by measuring malondialdehyde in the renal tissue. RESULTS: Grossly, the refluxing kidney was larger than the contralateral normal kidney, and the refluxing ureter was dilated and tortuous. Microscopy of tissues from the kidneys in group 3 showed apparent periglomerular mononuclear cell infiltration, tubular dilatation and atrophy, and interstitial fibrosis. The kidneys from groups 2, 4 and 5 showed mild mononuclear cell infiltration with no interstitial fibrosis. The level of malondialdehyde in the kidneys of group 3 was significantly higher than that in group 2, 4 and 5 (P < 0.05); the level in groups 4 and 5 did not differ significantly from that in group 2. CONCLUSIONS: This study shows that cranberries have an anti-inflammatory effect through their antioxidant function and might prevent infection-induced oxidative renal damage. Thus, clinically cranberries might be used as a beneficial adjuvant treatment to prevent damage due to pyelonephritis in children with VUR.

Reduction of bacteriuria and pyuria after ingestion of cranberry juice.

Posted: November 10, 2010
Authors: Avorn J, Monane M, Gurwitz JH, Glynn RJ, Choodnovskiy I, Lipsitz LA
Journal: JAMA 271(10):751-754

Abstract: OBJECTIVE: To determine the effect of regular intake of cranberry juice beverage on bacteriuria and pyuria in elderly women.

DESIGN: Randomized, double-blind, placebo-controlled trial.

SUBJECTS: Volunteer sample of 153 elderly women (mean age, 78.5 years).

INTERVENTION: Subjects were randomly assigned to consume 300 mL per day of a commercially available standard cranberry beverage or a specially prepared synthetic placebo drink that was indistinguishable in taste, appearance, and vitamin C content but lacked cranberry content.

OUTCOME MEASURES: A baseline urine sample and six clean-voided study urine samples were collected at approximately 1-month intervals and tested quantitatively for bacteriuria and the presence of white blood cells.

RESULTS: Subjects randomized to the cranberry beverage had odds of bacteriuria (defined as organisms numbering > or = 10(5)/mL) with pyuria that were only 42% of the odds in the control group (P = .004). Their odds of remaining bacteriuric-pyuric, given that they were bacteriuric-pyuric in the previous month, were only 27% of the odds in the control group (P = .006).

CONCLUSIONS: These findings suggest that use of a cranberry beverage reduces the frequency of bacteriuria with pyuria in older women. Prevalent beliefs about the effects of cranberry juice on the urinary tract may have microbiologic justification.

Safety and efficacy of cranberry (vaccinium macrocarpon) during pregnancy and lactation

Posted: November 10, 2010
Authors: Dugoua JJ, Seely D, Perri D, Mills E, Koren G
Journal: Can J Clin Pharmacol 15(1):e80-6

Abstract: BACKGROUND: There is a lack of basic knowledge on the part of both clinicians and patients as to the indications for use and safety of herbs used during pregnancy and lactation. This is one article in a series that systematically reviews the evidence for herbs commonly used during pregnancy and lactation. OBJECTIVES: To systematically review the literature for evidence on the use, safety and pharmacology of cranberry, focusing on issues pertaining to pregnancy and lactation. METHODS: We searched 7 electronic databases and compiled data according to the grade of evidence found. RESULTS: There is no direct evidence of safety or harm to the mother or fetus as a result of consuming cranberry during pregnancy. Indirectly, there is good scientific evidence that cranberry may be of minimal risk, where a survey of 400 pregnant women did not uncover any adverse events when cranberry was regularly consumed. In lactation, the safety or harm of cranberry is unknown. CONCLUSIONS: Women experience urinary tract infections with greater frequency during pregnancy. Given the evidence to support the use of cranberry for urinary tract infections (UTIs) and its safety profile, cranberry supplementation as fruit or fruit juice may be a valuable therapeutic choice in the treatment of UTIs during pregnancy.

Selected fruits reduce azoxymethane (AOM)-induced aberrant crypt foci (ACF) in Fisher 344 male rats.

Posted: November 10, 2010
Authors: Boateng J, Verghese M, Shackelford L, Walker LT, Khatiwada J, Ogutu S, Williams DS, Jones J, Guyton M, Asiamah D, Henderson F, Grant L, DeBruce M, Johnson A, Washington S, Chawan CB.
Journal: Food Chem Toxicol 45(5):725-32

Abstract: Phytochemicals contribute to the vibrant colors of fruits and it is suggested that the darker the fruit the higher the antioxidative or anticarcinogenic properties. In this study we investigated the possible effects of blueberries (BLU), blackberries (BLK), plums (PLM), mangoes (MAN), pomegranate juice (POJ), watermelon juice (WMJ) and cranberry juice (CBJ) on azoxymethane (AOM)-induced aberrant crypt foci (ACF) in Fisher 344 male rats. Forty-eight male Fisher 344 rats were randomly assigned to eight groups (n=6). The groups were fed AIN-93G as a control (C) diet, the rats fed fruits received AIN-93G+5% fruits and the groups that were given fruits juices received 20% fruit juice instead of water. The rats received subcutaneous injections of AOM at 16 mg/kg body weight at seventh and eighth weeks of age. At 17th week of age, the rats were killed by CO(2) asphyxiation. Total ACF numbers (mean+/-SEM) in the rats fed CON, BLU, BLK, PLM, MNG, POJ, WMJ and CBJ were 171.67+/-5.6, 11.33+/-2.85, 24.0+/-0.58, 33.67+/-0.89, 28.67+/-1.33, 15.67+/-1.86, 24.33+/-3.92 and 39.0+/-15.31. Total glutathione-S-transferase (GST) activity (mICROmol/mg) in the liver of the rats fed fruits (except BLK) and fruit juices were significantly (p<0.05) higher in the rats fed fruits and fruit juices compared with the control. Our findings suggest that among the fruits and fruit juices, BLU and POJ contributed to significant (P<0.05) reductions in the formation of AOM-induced ACF.

Urinary ionized calcium in urolithiasis. Effect of cranberry juice.

Posted: November 10, 2010
Authors: Light I, Gursel E, Zinnser HH
Journal: Urology 1(1):67-70

Abstract: Abstract: Urinary ionized calcium was determined by a calcium activity electrode in 32 normal persons and in 54 patients with calcium-containing renal stones and without urinary tract infection. It was found to be 38 per cent higher in patients with calcium-containing renal stone in comparison to normal persons. However, this was not statistically significant. No consistant change in total or ionized calcium excretion was produced in normal volunteers by the administration of as much as 5 pints of cranberry juice. In patients with renal stones, the urinary ionized calcium was reduced during the cranberry juice ingestion by 50 per cent, which was statistically highly significant.

Urinary tract infections: what's new

Posted: November 10, 2010
Authors: Krieger JN
Journal: J Urol 168(6):2351-8

Abstract: PURPOSE: This review provides practicing urologists with important basic information about urinary tract infections (UTIs) that can be applied to everyday clinical problems.

MATERIALS AND METHODS: A review is presented of provocative and controversial concepts in the current literature.

RESULTS: Bacterial virulence mechanisms are critical for overcoming the normal host defenses. Increasing antimicrobial resistance of uropathogens has led to reconsideration of traditional treatment recommendations in many areas. For effective patient management the first issue is to define complicating urological factors. Managing complicated urinary tract infections, particularly in urology, is determined by clinical experience to define the pertinent anatomy and to determine the optimal interventions. New clinical data are summarized on UTIs in long-term care patients, behavioral risks for UTI in healthy women and anatomical differences associated with an increased risk for UTI. The rationale is presented for UTI prophylaxis using cranberry juice, immunization and bacterial interference. Current treatment trends for UTI include empiric therapy (without urine culture and sensitivity testing), short-course therapy, patient-administered (self-start) therapy and outpatient therapy for uncomplicated pyelonephritis.

CONCLUSIONS: Recommendations for treating patients with UTIs have changed based on basic science and clinical experience.

A systematic review of the evidence for cranberries and blueberries in UTI prevention

Posted: November 9, 2010
Authors: Jepson RG, Craig JC
Journal: Mol Nutr Food Res 51(6):738-45

Abstract: In this review we assess the effectiveness of cranberry and blueberry products in preventing symptomatic urinary tract infections (UTIs). Selection criteria were randomised or quasi-randomised controlled trials of cranberry or blueberry juice/products for the prevention of symptomatic UTIs. A comprehensive search was undertaken in November 2006 whereupon two reviewers independently assessed and extracted data. Quality was assessed using Cochrane criteria. Relative risks (RR) were calculated where appropriate; otherwise a narrative synthesis was undertaken. No relevant trials of blueberry products were identified. Nine trials of cranberry products met the inclusion criteria. In four good quality randomised controlled trials (RCTs), cranberry products significantly reduced the incidence of symptomatic UTIs in 12 months (overall RR 0.65, 95% CI: 0.46-0.90) compared with placebo/control. Five trials were not included in the meta-analyses due to the lack of appropriate data. However, only one reported a significant result. Side effects were common, and losses to followup/withdrawals in several of the trials were high (> 40%). There is some evidence from four good quality RCTs that cranberry juice may decrease the number of symptomatic UTIs over a 12-month period, particularly in women with recurrent UTIs. It is uncertain whether it is effective in other susceptible groups.

Anticancer activities of cranberry phytochemicals: an update

Posted: November 9, 2010
Authors: Neto CC, Amoroso JW and Liberty AM
Journal: Mol Nutr Food Res 52(Suppl 1):S18-27

Abstract: Studies employing mainly in vitro tumor models show that extracts and compounds isolated from cranberry fruit (Vaccinium macrocarpon) inhibit the growth and proliferation of several types of tumor including breast, colon, prostate, and lung. Proanthocyanidin oligomers, flavonol and anthocyanin glycosides and triterpenoids are all likely contributors to the observed anticancer properties and may act in a complementary fashion to limit carcinogenesis. Possible chemopreventive mechanisms of action by cranberry phytochemicals include induction of apoptosis in tumor cells, reduced ornithine decarboxylase activity, decreased expression of matrix metalloproteinases associated with prostate tumor metastasis, and anti-inflammatory activities including inhibition of cyclooxygenases. A review of recent studies suggests a potential role for cranberry as a dietary chemopreventive and provides direction for future research.

Antiviral effects on bacteriophages and rotavirus by cranberry juice.

Posted: November 9, 2010
Authors: Lipson SM, Sethi L, Cohen P, Gordon RE, Tan IP, Burdowski A, Stotzky G.
Journal: Phytomedicine 14(1):23-30

Abstract: Studies were undertaken to investigate the antiviral effects of comestible juices, especially cranberry juice, on non-related viral species. After exposure of bacteriophage T2 to a commercially available cranberry (Vaccinium macrocarpon) juice cocktail (CJ), virus infectivity titer was no longer detectible. After a 60-min exposure to orange (OJ) and grapefruit juices (GJ), phage infectivity was reduced to 25-35% of control, respectively. Similar data were observed for the bacteriophage T4. CJ inactivation of phage T4 was rapid, dose-dependent, and occurred at either 4 or 23 degrees C. Neither pH nor differences in sugar/carbohydrate levels among the juices may be ascribed to the recognized antiviral effects. Further studies were performed to identify the occurrence of antiviral activity by CJ to a mammalian enteric virus. The treatment of the simian rotavirus SA-11 with a 20% CJ suspension was sufficient to inhibit hemagglutination. Under scanning and transmission electron microscopy, CJ was observed to inhibit the adsorption of phage T4 to its bacterial host cells and prevented the replication of rotavirus in its monkey kidney (MA-104) host cells, respectively. The data suggest, for the first time, a non-specific antiviral effect towards unrelated viral species (viz., bacteriophages T2 and T4 and the simian rotavirus SA-11) by a commercially available cranberry fruit juice drink.

Berries: emerging impact on cardiovascular health.

Posted: November 9, 2010
Authors: Basu A, Rhone M, Lyons TJ.
Journal: Nutr Rev 68(3):168-77

Abstract: Berries are a good source of polyphenols, especially anthocyanins, micronutrients, and fiber. In epidemiological and clinical studies, these constituents have been associated with improved cardiovascular risk profiles. Human intervention studies using chokeberries, cranberries, blueberries, and strawberries (either fresh, or as juice, or freeze-dried), or purified anthocyanin extracts have demonstrated significant improvements in LDL oxidation, lipid peroxidation, total plasma antioxidant capacity, dyslipidemia, and glucose metabolism. Benefits were seen in healthy subjects and in those with existing metabolic risk factors. Underlying mechanisms for these beneficial effects are believed to include upregulation of endothelial nitric oxide synthase, decreased activities of carbohydrate digestive enzymes, decreased oxidative stress, and inhibition of inflammatory gene expression and foam cell formation. Though limited, these data support the recommendation of berries as an essential fruit group in a heart-healthy diet.

Bioactive compounds in cranberries and their role in prevention of urinary tract infections.

Posted: November 9, 2010
Authors: Howell AB
Journal: Mol Nutr Food Res 51(6):732-7

Abstract: Cranberry (Vaccinium macrocarpon Ait.) ingestion has long been associated with prevention of urinary tract infections. The beneficial mechanism was historically thought to be due to the fruit acids causing a bacteriostatic effect in the urine. However, recently, a group of proanthocyanidins (PACs) with A-type linkages were isolated from cranberry which exhibit bacterial antiadhesion activity against both antibiotic susceptible and resistant strains of uropathogenic P-fimbriated Escherichia coli bacteria. The link between cranberry ingestion and maintenance of urinary tract health as well as the structural diversity, pharmacokinetics, quantification, and bacterial antiadhesion bioactivity of the A-linked cranberry PACs are reviewed.

Cranberries (Vaccinium macrocarpon) and cardiovascular disease risk factors

Posted: November 9, 2010
Authors: McKay DL, Blumberg JB.
Journal: Nutr Rev 65(11):490-502

Abstract: The American cranberry (Vaccinium macrocarpon) is one of the three commercially important fruits native to North America. Cranberries are a particularly rich source of phenolic phytochemicals, including phenolic acids (benzoic, hydroxycinnamic, and ellagic acids) and flavonoids (anthocyanins, flavonols, and flavan-3-ols). A growing body of evidence suggests that polyphenols, including those found in cranberries, may contribute to reducing the risk of cardiovascular disease (CVD) by increasing the resistance of LDL to oxidation, inhibiting platelet aggregation, reducing blood pressure, and via other anti-thrombotic and anti-inflammatory mechanisms. Research regarding the bioactivity of cranberries and their constituents on risk factors for CVD is reviewed.

Cranberry and blueberry: evidence for protective effects against cancer and vascular diseases.

Posted: November 9, 2010
Authors: Neto CC
Journal: Mol Nutr Food Res 51(6):652-64

Abstract: Growing evidence from tissue culture, animal, and clinical models suggests that the flavonoid-rich fruits of the North American cranberry and blueberry (Vaccinium spp.) have the potential ability to limit the development and severity of certain cancers and vascular diseases including atherosclerosis, ischemic stroke, and neurodegenerative diseases of aging. The fruits contain a variety of phytochemicals that could contribute to these protective effects, including flavonoids such as anthocyanins, flavonols, and proanthocyanidins; substituted cinnamic acids and stilbenes; and triterpenoids such as ursolic acid and its esters. Cranberry and blueberry constituents are likely to act by mechanisms that counteract oxidative stress, decrease inflammation, and modulate macromolecular interactions and expression of genes associated with disease processes. The evidence suggests a potential role for dietary cranberry and blueberry in the prevention of cancer and vascular diseases, justifying further research to determine how the bioavailability and metabolism of berry phytonutrients influence their activity in vivo.

Cranberry and its phytochemicals: a review of in vitro anticancer studies

Posted: November 9, 2010
Authors: Neto CC
Journal: J Nutr 137(1 Suppl):186S-193S

Abstract: This article reviews the existing research on the anticancer properties of cranberry fruit and key phytochemicals that are likely contributors to chemoprevention. Results from in vitro studies using a variety of tumor models show that polyphenolic extracts from Vaccinium macrocarpon inhibit the growth and proliferation of breast, colon, prostate, lung, and other tumors, as do flavonols, proanthocyanidin oligomers, and triterpenoids isolated from the fruit. The unique combination of phytochemicals found in cranberry fruit may produce synergistic health benefits. Possible chemopreventive mechanisms of action by cranberry phytochemicals include induction of apoptosis in tumor cells, reduced ornithine decarboxylase activity, decreased expression of matrix metalloproteinases associated with prostate tumor metastasis, and antiinflammatory activities including inhibition of cyclooxygenases. These findings suggest a potential role for cranberry as a dietary chemopreventive and provide direction for future research.

Cranberry does not affect prothrombin time in male subjects on warfarin.

Posted: November 9, 2010
Authors: Li Z, Seeram NP, Carpenter CL, Thames G, Minutti C, Bowerman S.
Journal: J Am Diet Assoc 106(12):2057-61

Abstract: There have been case reports suggesting that cranberry beverages may interact with warfarin. To date, no research study has been conducted to examine the potential interaction of cranberry and warfarin. The current study is a randomized, placebo-controlled, double-blind, crossover study to investigate the effect of cranberry juice on prothrombin time as assessed by the international normalized ratio (INR). Seven subjects with atrial fibrillation on a stable dose of warfarin for 3 months were randomized to consume 250 mL of cranberry juice for 7 days, then placebo for 7 days, or vice versa. The washout period was 7 days. The prothrombin time/INR was measured at baseline, and on days 2, 4, 7, 10, 14, 16, 18, 21, and 24. Data were analyzed by the Student t test for paired values. The baseline INR was 2.28+/-0.54 for the cranberry group and 2.13+/-0.50 for the placebo group. For all test points, the INR did not change significantly from baseline. At day 7 on cranberry juice, the INR was 2.23+/-0.53 for cranberry first group and 2.16+/-0.40 for placebo first group. The mean differences between the cranberry and placebo groups were not statistically significant. Our results suggest no significant interaction between the daily consumption of 250 mL cranberry juice and warfarin. When counseling patients on dietary changes necessary during warfarin treatment, it does not seem necessary to eliminate daily cranberry juice consumption at amounts of 250 mL, but the INR should be followed up closely.

Cranberry juice constituents impair lymphoma growth and augment the generation of antilymphoma antibodies in syngeneic mice

Posted: November 9, 2010
Authors: Hochman N, Houri-Haddad Y, Koblinski J, Wahl L, Roniger M, Bar-Sinai A, Weiss EI, Hochman J
Journal: Nutr Cancer 60(4):511-7

Abstract: In addition to its nutritional value, cranberry juice has been effective in treating urinary tract infections. Various reports have also demonstrated its potential for inhibiting in vitro growth of transformed cell lines. Here we show that a fraction [nondialyzable material (NDM) of a molecular weight range 12,000-30,000 (NDM 12-30K)] derived from cranberry juice impairs in vitro growth and invasion through extracellular matrix of Rev-2-T-6 murine lymphoma cells. Furthermore, intraperitoneal injection of this fraction at nontoxic doses both inhibits the growth of Rev-2-T-6 tumors in vivo and enhances the generation of antilymphoma antibodies. These findings demonstrate the in vivo efficacy of cranberry components against malignant lymphoma in immune competent hosts.

Cranberry proanthocyanidins induce apoptosis and inhibit acid-induced proliferation of human esophageal adenocarcinoma cells.

Posted: November 9, 2010
Authors: Kresty LA, Howell AB, Baird M
Journal: J Agric Food Chem 56(3):676-80

Abstract: The occurrence of esophageal adenocarcinoma and its only recognized precursor lesion, Barrett's esophagus, has rapidly increased during the past three decades. The precise reason for the rise remains to be elucidated, but increasing rates have been linked to multiple nutritional factors. Plant-based diets have generally been associated with a reduction of risk for esophageal adenocarcinoma and those of animal origin with risk escalation. Moreover, a number of recent in vitro and limited in vivo investigations have reported that cranberry extracts affect multiple cancer-associated processes in breast, colon, prostate, and other cancer cell lines of epithelial origin. Thus, this study sought to investigate the chemopreventive potential of a cranberry proanthocyanidin rich extract (PAC) in SEG-1 human esophageal adenocarcinoma (EAC) cells. PAC pretreatment significantly inhibited the viability and proliferation of EAC cells in a time- and dose-dependent manner. Moreover, PAC (50 microg/mL) significantly inhibited acid-induced cell proliferation of SEG-1 cells. PAC treatment induced cell cycle arrest at the G1 checkpoint and significantly reduced the percentage of SEG-1 cells in S-phase following 24 and 48 h of exposure. PAC treatment also resulted in significant induction of apoptosis. Thus, PAC modulates cell cycle regulation, aberrant proliferation, and apoptosis, all key biological processes altered during progression to esophageal adenocarcinoma. These findings support that further mechanistic studies are warranted to more fully elucidate the inhibitory potential of PAC against esophageal cancer.

Effects of daily ingestion of cranberry juice on the pharmacokinetics of warfarin, tizanidine, and midazolam--probes of CYP2C9, CYP1A2, and CYP3A4

Posted: November 9, 2010
Authors: Lilja JJ, Backman JT, Neuvonen PJ
Journal: Clin Pharmacol Ther 81(6):833-9

Abstract: Case reports suggest that cranberry juice can increase the anticoagulant effect of warfarin. We investigated the effects of cranberry juice on R-S-warfarin, tizanidine, and midazolam; probes of CYP2C9, CYP1A2, and CYP3A4. Ten healthy volunteers took 200 ml cranberry juice or water t.i.d. for 10 days. On day 5, they ingested 10 mg racemic R-S-warfarin, 1 mg tizanidine, and 0.5 mg midazolam, with juice or water, followed by monitoring of drug concentrations and thromboplastin time. Cranberry juice did not increase the peak plasma concentration or area under concentration-time curve (AUC) of the probe drugs or their metabolites, but slightly decreased (7%; P=0.051) the AUC of S-warfarin. Cranberry juice did not change the anticoagulant effect of warfarin. Daily ingestion of cranberry juice does not inhibit the activities of CYP2C9, CYP1A2, or CYP3A4. A pharmacokinetic mechanism for the cranberry juice-warfarin interaction seems unlikely.

Impact of cranberry on Escherichia coli cellular surface characteristics

Posted: November 9, 2010
Authors: Johnson BJ, Lin B, Dinderman MA, Rubin RA, Malanoski AP, Ligler FS
Journal: Biochem Biophys Res Comm 377(3):992-4

Abstract: The anti-adhesive effects of cranberry have been attributed to both interactions of its components with the surface of bacterial cells and to inhibition of p-fimbriae expression. Previous reports also suggested that the presence of cranberry juice changed the Gram stain characteristics of Escherichia coli. Here, we show that the morphology of E. coli is changed when grown in the presence of juice or extract from Vaccinium macrocarpon (cranberry). Gene expression analysis indicates the down regulation of flagellar basal body rod and motor proteins. Consistent with this finding and previous reports, the SEM images indicate a decrease in the visible p-fimbriae. The iodine used in Gram-staining protocols was found to interact differently with the bacterial membrane when cells were cultured in spiked media. Slight alterations in the Gram stain protocol demonstrated that culturing in the presence of cranberry juice does not change the Gram stain characteristics contradicting other reports.

In-vitro and in-vivo evidence of dose-dependent decrease of uropathogenic Escherichia coli virulence after consumption of commercial Vaccinium macrocarpon (cranberry) capsules.

Posted: November 9, 2010
Authors: Lavigne JP, Bourg G, Combescure C, Botto H, Sotto A
Journal: Clin Microbiol Infect 14(4):350-355

Abstract: This study evaluated the antibacterial efficacy of the consumption of cranberry capsules vs. placebo in the urine of healthy volunteers. A first double-blind, randomised, crossover trial involved eight volunteers who had followed three regimens, with or without cranberry, with a wash-out period of at least 6 days between each regimen. Twelve hours after consumption of cranberry or placebo hard capsules, the first urine of the morning was collected. Different Escherichia coli strains were cultured in the urine samples. Urinary antibacterial adhesion activity was measured in vitro using the human T24 epithelial cell-line, and in vivo using the Caenorhabditis elegans killing model. With the in-vitro model, 108 mg of cranberry induced a significant reduction in bacterial adherence to T24 cells as compared with placebo (p <0.001). A significant dose-dependent decrease in bacterial adherence in vitro was noted after the consumption of 108 and 36 mg of cranberry (p <0.001). The in-vivo model confirmed that E. coli strains had a reduced ability to kill C. elegans after growth in the urine of patients who consumed cranberry capsules. Overall, these in-vivo and in-vitro studies suggested that consumption of cranberry juice represents an interesting new strategy to prevent recurrent urinary tract infection.

Pharmacodynamic interaction of warfarin with cranberry but not with garlic in healthy subjects2

Posted: November 9, 2010
Authors: Mohammed Abdul MI, Jiang X, Williams KM, Day RO, Roufogalis BD, Liauw WS, Xu H, McLachlan AJ
Journal: Br J Pharmacol 154(8):1691-700

Abstract: BACKGROUND AND PURPOSE: Patients commonly take complementary medicines in conjunction with warfarin yet evidence supporting the safety or the risk of a herb-drug interaction is lacking. The aim of this study was to investigate the possible impact of two commonly used herbal medicines, garlic and cranberry, on the pharmacokinetics and pharmacodynamics of warfarin in healthy male subjects.

EXPERIMENTAL APPROACH: An open-label, three-treatment, randomized crossover clinical trial was undertaken and involved 12 healthy male subjects of known CYP2C9 and VKORC1 genotype. A single dose of 25 mg warfarin was administered alone or after 2 weeks of pretreatment with either garlic or cranberry. Warfarin enantiomer concentrations, INR, platelet aggregation and clotting factor activity were measured to assess pharmacokinetic and pharmacodynamic interactions between warfarin and herbal medicines.

KEY RESULTS: Cranberry significantly increased the area under the INR-time curve by 30% when administered with warfarin compared with treatment with warfarin alone. Cranberry did not alter S- or R-warfarin pharmacokinetics or plasma protein binding. Co-administration of garlic did not significantly alter warfarin pharmacokinetics or pharmacodynamics. Both herbal medicines showed some evidence of VKORC1 (not CYP2C9) genotype-dependent interactions with warfarin, which is worthy of further investigation.

CONCLUSIONS AND IMPLICATIONS: Cranberry alters the pharmacodynamics of warfarin with the potential to increase its effects significantly. Co-administration of warfarin and cranberry requires careful monitoring.

Spinal-injured neuropathic bladder antisepsis (SINBA) trial

Posted: November 9, 2010
Authors: Lee BB, Haran MJ, Hunt LM, Simpson JM, Marial O, Rutkowski SB, Middleton JW, Kotsiou G, Tudehope M, Cameron ID
Journal: Spinal Cord 45(8):542-50

Abstract: OBJECTIVE: To determine whether Methenamine Hippurate (MH) or cranberry tablets prevent urinary tract infections (UTI) in people with neuropathic bladder following spinal cord injury (SCI).

STUDY DESIGN: Double-blind factorial-design randomized controlled trial (RCT) with 2 year recruitment period from November 2000 and 6 month follow-up.

SETTING: In total, 543 eligible predominantly community dwelling patients were invited to participate in the study, of whom 305 (56%) agreed.

METHODS: Eligible participants were people with SCI with neurogenic bladder and stable bladder management. All regimens were indistinguishable in appearance and taste. The dose of MH used was 1 g twice-daily. The dose of cranberry used was 800 mg twice-daily. The main outcome measure was the time to occurrence of a symptomatic UTI.

RESULTS: Multivariate analysis revealed that patients randomized to MH did not have a significantly longer UTI-free period compared to placebo (HR 0.96, 95% CI: 0.68-1.35, P=0.75). Patients randomized to cranberry likewise did not have significantly longer UTI-free period compared to placebo (HR 0.93, 95% CI: 0.67-1.31, P=0.70).

CONCLUSION: There is no benefit in the prevention of UTI from the addition of MH or cranberry tablets to the usual regimen of patients with neuropathic bladder following SCI.

A randomized trial to evaluate effectiveness and cost effectiveness of naturopathic cranberry products as prophylaxis against urinary tract infection in women

Posted: November 8, 2010
Authors: Stothers L
Journal: Can J Urol 9(3):1558-62

Abstract: PURPOSE: To determine, from a societal perspective, the effectiveness and cost effectiveness of concentrated cranberry tablets, versus cranberry juice, versus placebo used as prophylaxis against lower urinary tract infection (UTI) in adult women.MATERIALS AND METHODS: One hundred fifty sexually active women aged 21 through 72 years were randomized for one year to one of three groups of prophylaxis: placebo juice + placebo tablets versus placebo juice + cranberry tablets, versus cranberry juice + placebo tablets. Tablets were taken twice daily, juice 250 ml three times daily. Outcome measures were: (1) a >50% decrease in symptomatic UTI's per year (symptoms + >or= 100 000 single organisms/ml) and (2) a >50% decrease in annual antibiotic consumption. Cost effectiveness was calculated as dollar cost per urinary tract infection prevented. Stochastic tree decision analytic modeling was used to identify specific clinical scenarios for cost savings.RESULTS: Both cranberry juice and cranberry tablets statistically significantly decreased the number of patients experiencing at least 1 symptomatic UTI/year (to 20% and 18% respectively) compared with placebo (to 32%) (p<0.05). The mean annual cost of prophylaxis was $624 and $1400 for cranberry tablets and juice respectively. Cost savings were greatest when patients experienced >2 symptomatic UTI's per year (assuming 3 days antibiotic coverage) and had >2 days of missed work or required protective undergarments for urgency incontinence. Total antibiotic consumption was less annually in both treatment groups compared with placebo. Cost effectiveness ratios demonstrated cranberry tablets were twice as cost effective as organic juice for prevention.CONCLUSIONS: Cranberry tablets provided the most cost-effective prevention for UTI.

An examination of the anti-adherence activity of cranberry juice on urinary and nonurinary bacterial isolates

Posted: November 8, 2010
Authors: Schmidt DR, Sobota AE
Journal: Microbios 55(224-225):173-81

Abstract: In a previous investigation it was demonstrated that cranberry juice cocktail was able to inhibit adherence in 77 clinical isolates of Escherichia coli obtained from patients with diagnosed urinary tract infections. This work has been extended to include clinical isolates of E. coli, Proteus, Klebsiella, Enterobacter and Pseudomonas isolated from urine, sputum, wound and stool. Bacterial strains isolated from urine adhere in greater numbers to urinary tract epithelial cells than organisms isolated from sputum, stool and wound sources. E. coli, isolated from urine, adheres to urinary epithelial cells, in numbers three times greater than E. coli isolated from other clinical sources, and thus appears to represent a unique population of cells in terms of adherence. Cranberry juice cocktail and urine and urinary epithelial cells obtained after drinking the cocktail all demonstrate antiadherence activity against Gram-negative rods isolated from urine and other clinical sources. Drinking the cocktail may be useful in managing urinary tract infections in certain patients.

Anthocyanins are bioavailable in humans following an acute dose of cranberry juice

Posted: November 8, 2010
Authors: Milbury PE, Vita JA, Blumberg JB
Journal: J Nutr 140(6):1099-1104

Abstract: Research suggests that anthocyanins from berry fruit may affect a variety of physiological responses, including endothelial function, but little information is available regarding the pharmacokinetics of these flavonoids in humans. To determine the pharmacokinetics of cranberry anthocyanins, a study was undertaken in 15 participants (age: 62 +/- 8 y) with coronary artery disease. Blood and urine samples were collected between baseline (0 h) and 4 h after consumption of 480 mL cranberry juice (54% juice; 835 mg total polyphenols; 94.47 mg anthocyanins). Marked inter-individual differences in plasma anthocyanin pharmacokinetics were observed with maximum anthocyanin concentrations detected between 1 and 3 h. Cranberry anthocyanins were bioavailable but with notable differences in the maximum concentration and area under the curve(0-4h) between individual participants. The pattern of anthocyanin glucosides observed in plasma and urine generally reflected the relative concentration determined in the juice. Plasma concentrations of the individual anthocyanins ranged between 0.56 and 4.64 nmol/L. Total recovery of urinary anthocyanin was 0.79 +/- 0.90% of the dose delivered. These data are in agreement with the pharmacokinetics of anthocyanins from other foods suggesting that cranberry anthocyanins are poorly absorbed and rapidly removed from plasma. Observed concentrations of plasma anthocyanins appear insufficient to alter radical load or redox potential but may be adequate to affect signal transduction and/or gene expression.

Blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry extracts inhibit growth and stimulate apoptosis of human cancer cells in vitro

Posted: November 8, 2010
Authors: Seeram NP, Adams LS, Zhang Y, Lee R, Sand D, Scheuller HS, Heber D
Journal: J Agric Food Chem 54(25):9329-39

Abstract: Berry fruits are widely consumed in our diet and have attracted much attention due to their potential human health benefits. Berries contain a diverse range of phytochemicals with biological properties such as antioxidant, anticancer, anti-neurodegerative, and anti-inflammatory activities. In the current study, extracts of six popularly consumed berries--blackberry, black raspberry, blueberry, cranberry, red raspberry and strawberry--were evaluated for their phenolic constituents using high performance liquid chromatography with ultraviolet (HPLC-UV) and electrospray ionization mass spectrometry (LC-ESI-MS) detection. The major classes of berry phenolics were anthocyanins, flavonols, flavanols, ellagitannins, gallotannins, proanthocyanidins, and phenolic acids. The berry extracts were evaluated for their ability to inhibit the growth of human oral (KB, CAL-27), breast (MCF-7), colon (HT-29, HCT116), and prostate (LNCaP) tumor cell lines at concentrations ranging from 25 to 200 micro g/mL. With increasing concentration of berry extract, increasing inhibition of cell proliferation in all of the cell lines were observed, with different degrees of potency between cell lines. The berry extracts were also evaluated for their ability to stimulate apoptosis of the COX-2 expressing colon cancer cell line, HT-29. Black raspberry and strawberry extracts showed the most significant pro-apoptotic effects against this cell line. The data provided by the current study and from other laboratories warrants further investigation into the chemopreventive and chemotherapeutic effects of berries using in vivo models.

Cranberry changes the physicochemical surface properties of E. coli and adhesion with uroepithelial cells

Posted: November 8, 2010
Authors: Liu Y, Gallardo-Moreno AM, Pinzon-Arango PA, Reynolds Y, Rodriguez G, Camesano TA.
Journal: Colloids Surface B 65(1):35-42

Abstract: Cranberries have been suggested to decrease the attachment of bacteria to uroepithelial cells (UC), thus preventing urinary tract infections, although the mechanisms are not well understood. A thermodynamic approach was used to calculate the Gibbs free energy of adhesion changes (DeltaG(adh)) for bacteria-UC interactions, based on measuring contact angles with three probe liquids. Interfacial tensions and DeltaG(adh) values were calculated for Escherichia coli HB101pDC1 (P-fimbriated) and HB101 (non-fimbriated) exposed to cranberry juice (0-27 wt.%). HB101pDC1 can form strong bonds with the Gal-Gal disaccharide receptor on uroepithelial cells, while HB101-UC interactions are only non-specific. For HB101 interacting with UC, DeltaG(adh) was always negative, suggesting favorable adhesion, and the values were insensitive to cranberry juice concentration. For the HB101pDC1-UC system, DeltaG(adh) became positive at 27wt.% cranberry juice, suggesting that adhesion was unfavorable. Acid-base (AB) interactions dominated the interfacial tensions, compared to Lifshitz-van der Waals (LW) interactions. Exposure to cranberry juice increased the AB component of the interfacial tension of HB101pDC1. LW interactions were small and insensitive to cranberry juice concentration. The number of bacteria attached to UC was quantified in batch adhesion assays and quantitatively correlated with DeltaG(adh). Since the thermodynamic approach should not agree with the experimental results when specific interactions are present, such as HB101pDC-UC ligand-receptor bonds, our results may suggest that cranberry juice disrupts bacterial ligand-UC receptor binding. These results help form the mechanistic explanation of how cranberry products can be used to prevent bacterial attachment to host tissue, and may lead to the development of better therapies based on natural products.

Cranberry for prevention of urinary tract infections

Posted: November 8, 2010
Authors: Lynch DM
Journal: Am Fam Physician 70(11):2175-7

Abstract: Traditionally, cranberry has been used for the treatment and prophylaxis of urinary tract infections. Research suggests that its mechanism of action is preventing bacterial adherence to host cell surface membranes. Systematic reviews have concluded that no reliable evidence supports the use of cranberry in the treatment or prophylaxis of urinary tract infections; however, more recent, randomized controlled trials demonstrate evidence of cranberry's utility in urinary tract infection prophylaxis. Supporting studies in humans are lacking for other clinical uses of cranberry. Cranberry is a safe, well-tolerated herbal supplement that does not have significant drug interactions.

Direct adhesion force measurements between E. coli and human uroepithelial cells in cranberry juice cocktail

Posted: November 8, 2010
Authors: Liu Y, Pinzón-Arango PA, Gallardo-Moreno AM, Camesano TA
Journal: Mol Nutr Food Res 54(12):1744-1752

Abstract: Scope: Atomic force microscopy (AFM) was used to directly measure the nanoscale adhesion forces between P-fimbriated Escherichia coli (E. coli) and human uroepithelial cells exposed to cranberry juice, in order to reveal the molecular mechanisms by which cranberry juice cocktail (CJC) affects bacterial adhesion.Methods and results: Bacterial cell probes were created by attaching P-fimbriated E. coli HB101pDC1 or non-fimbriated E. coli HB101 to AFM tips, and the cellular probes were used to directly measure the adhesion forces between E. coli and uroepithelial cells in solutions containing: 0, 2.5, 5, 10, and 27 wt% CJC. Macroscale attachment of E. coli to uroepithelial cells was measured and correlated to nanoscale adhesion force measurements. The adhesion forces between E. coli HB101pDC1 and uroepithelial cells were dose-dependent, and decreased from 9.32+/-2.37 nN in the absence of CJC to 0.75+/-0.19 nN in 27 wt% CJC. Adhesion forces between E. coli HB101 and uroepithelial cells were low in buffer (0.74+/-0.18 nN), and did not change significantly in CJC (0.78+/-0.18 nN in 27 wt% CJC; P=0.794).Conclusion: Our study shows that CJC significantly decreases nanoscale adhesion forces between P-fimbriated E. coli and uroepithelial cells.

Effect of cranberry juice concentrate on chemically-induced urinary bladder cancers.

Posted: November 8, 2010
Authors: Prasain JK, Jones K, Moore R, Barnes S, Leahy M, Roderick R, Juliana MM, Grubbs CJ
Journal: Oncol Rep 19(6):1565-70

Abstract: The chemopreventive efficacy of cranberry juice concentrate in an experimental model of urinary bladder cancer was evaluated using female Fischer-344 rats. The animals received N-butyl-N-(4-hydroxybutyl)-nitrosamine (OH-BBN) for a period of eight weeks. Cranberry juice concentrate was administered at doses of 1.0 or 0.5 ml/rat/day beginning one week after the final OH-BBN treatment and continuing until the end of the study. The urinary bladders of all the rats were weighed and examined grossly for lesions, and all masses were submitted for pathological evaluation. A dose-dependent preventive effect of cranberry treatment was observed, with a reduced number of urinary bladder cancers (38%) in the 1.0 ml/rat/day group versus the control group. The cranberry extract neither affected body weight gain nor caused other signs of toxicity. For the metabolic studies, serum and urine were collected at 4 and 12 h after the administration of the cranberry juice concentrate and were analyzed by LC-MS/MS. Quercetin and its methylated derivative were detected in the urine samples. However, no quercetin was detected in the serum samples, indicating its poor bioavailability. These data suggest that components of cranberries may be effective in preventing urinary bladder carcinogenesis.

Efficacy of cranberry capsules in prevention of urinary tract infections in postmenopausal women

Posted: November 8, 2010
Authors: Mazokopakis EE
Journal: J Altern Complement Med 15(11):1155

Abstract: No abstract - Purpose: The aim of our correspondence is to submit the results of a small study (the first in a Greek population to our knowledge) about administering cranberries in the form of capsules to healthy postmenopausal women with recurrent UTIs.

Evaluation of cranberry supplement for reduction of urinary tract infections in individuals with neurogenic bladders secondary to spinal cord injury. A prospective, double-blinded, placebo-controlled, crossover study

Posted: November 8, 2010
Authors: Linsenmeyer TA, Harrison B, Oakley A, Kirshblum S, Stock JA, Millis SR
Journal: J Spinal Cord Med 27(1):29-34

Abstract: OBJECTIVE: To determine the effectiveness of cranberry supplement at preventing urinary tract infections (UTIs) in persons with spinal cord injury (SCI).

DESIGN: A prospective, double-blinded, placebo-controlled, crossover study.

PARTICIPANTS: 21 individuals with neurogenic bladders secondary to SCI.

MAIN OUTCOME MEASURES: Favorable or unfavorable response of cranberry supplement vs placebo on urinary bacterial counts and white blood cell (WBC) counts and the combination of bacterial and WBC counts.

METHODS: Individuals with neurogenic bladders due to SCI were recruited and randomly assigned to standardized 400-mg cranberry tablets or placebo 3 times a day for 4 weeks. After 4 weeks and an additional 1-week ""washout period,"" participants were crossed over to the other group. Participants were seen weekly, during which a urine analysis was obtained. UTI was defined as significant bacterial or yeast colony counts in the urine and elevated WBC counts (WBC count > or = 10 per high power field) in centrifuged urine. Participants with symptomatic infections were treated with appropriate antibiotics for 7 days and restarted on the cranberry tablet/ placebo after a 7-day washout period. Urinary pH between the cranberry and placebo groups was compared weekly. Data were analyzed using the Ezzet and Whitehead's random effect approach.

RESULTS: There was no statistically significant treatment (favorable) effect for cranberry supplement beyond placebo when evaluating the 2 treatment groups for bacterial count, WBC count, or WBC and bacterial counts in combination. Urinary pH did not differ between the placebo and cranberry groups.

CONCLUSION: Cranberry tablets were not found to be effective at changing urinary pH or reducing bacterial counts, urinary WBC counts, or UTIs in individuals with neurogenic bladders. Further long-term studies evaluating specific types of bladder management and UTIs will help to determine whether there is any role for the use of cranberries in individuals with neurogenic bladders.

Influence of cranberry juice on the urinary risk factors for calcium oxalate kidney stone formation

Posted: November 8, 2010
Authors: McHarg T, Rodgers A, Charlton K.
Journal: BJU Int 92(7):765-8

Abstract: OBJECTIVE: To investigate the potential influence of cranberry juice on urinary biochemical and physicochemical risk factors associated with the formation of calcium oxalate kidney stones, as this product might affect the chemical composition of urine.

SUBJECTS AND METHODS: Urinary variables were assessed in a randomized cross-over trial in 20 South African men (students) with no previous history of kidney stones. The first group of 10 subjects drank 500 mL of cranberry juice diluted with 1500 mL tap water for 2 weeks, while the second group drank 2000 mL of tap water for the same period. This was followed by a 2-week 'washout' period before the two groups crossed over. During the experimental phase subjects kept a 3-day food diary to assess their dietary and fluid intakes; 24-h urine samples were collected at baseline and on day 14 of the trial periods, and analysed using modern laboratory techniques. Urine analysis data were used to calculate the relative urinary supersaturations of calcium oxalate, uric acid and calcium phosphate. Data were assessed statistically by analysis of variance.

RESULTS: The ingestion of cranberry juice significantly and uniquely altered three key urinary risk factors. Oxalate and phosphate excretion decreased while citrate excretion increased. In addition, there was a decrease in the relative supersaturation of calcium oxalate, which tended to be significantly lower than that induced by water alone.

CONCLUSION: Cranberry juice has antilithogenic properties and, as such, deserves consideration as a conservative therapeutic protocol in managing calcium oxalate urolithiasis.

Inhibition of Helicobacter pylori and associated urease by oregano and cranberry phytochemical synergies.

Posted: November 8, 2010
Authors: Lin YT, Kwon YI, Labbe RG, Shetty K
Journal: Appl Environ Microbiol 71(12):8558-64

Abstract: Ulcer-associated dyspepsia is caused by infection with Helicobacter pylori. H. pylori is linked to a majority of peptic ulcers. Antibiotic treatment does not always inhibit or kill H. pylori with potential for antibiotic resistance. The objective of this study was to determine the potential for using phenolic phytochemical extracts to inhibit H. pylori in a laboratory medium. Our approach involved the development of a specific phenolic profile with optimization of different ratios of extract mixtures from oregano and cranberry. Subsequently, antimicrobial activity and antimicrobial-linked urease inhibition ability were evaluated. The results indicated that the antimicrobial activity was greater in extract mixtures than in individual extracts of each species. The results also indicate that the synergistic contribution of oregano and cranberry phenolics may be more important for inhibition than any species-specific phenolic concentration. Further, based on plate assay, the likely mode of action may be through urease inhibition and disruption of energy production by inhibition of proline dehydrogenase at the plasma membrane.

Interaction potential between cranberry juice and warfarin

Posted: November 8, 2010
Authors: Pham DQ, Pham AQ
Journal: Am J Health Syst Pharm 64(5):490-4

Abstract: PURPOSE: The interaction potential between warfarin and cranberry juice is discussed.

SUMMARY: Reports from the United Kingdom have raised concern over the interaction potential between cranberry juice and warfarin. Warfarin is the most commonly prescribed oral medication for anticoagulation therapy. Cranberry juice is a flavonoid, which has been shown to induce, inhibit, or act as a substrate for the biosynthesis of several cytochrome P-450 (CYP) isoenzymes. Specifically, cranberry juice may inhibit the activity of CYP2C9, the primary isoenzyme involved in the metabolism of S-warfarin. A search of the medical literature identified three peer-reviewed case reports and two peer-reviewed, prospective, randomized, placebo-controlled clinical trials using metabolic surrogates of warfarin (flurbiprofen and cyclosporine) that described possible interactions between cranberry juice and warfarin. Two case reports suggested that cranberry juice increased the International Normalized Ratio (INR) of patients taking warfarin, but neither clearly identified cranberry juice as the sole cause of INR elevation. One case report appeared to show a correlation between the effects of cranberry juice and warfarin metabolism. Both clinical trials indicated the lack of an interaction between cranberry juice and CYP isoenzymes 2C9 and 3A, both of which are necessary in warfarin metabolism. More studies are required to determine the potential interaction between cranberry juice and warfarin.

CONCLUSION: The available data do not seem to show a clinically relevant interaction between cranberry juice and warfarin; however, patients taking warfarin with cranberry juice should be cautioned about the potential interaction and monitored closely for INR changes and signs and symptoms of bleeding.

Preventive effect of a pectic polysaccharide of the common cranberry Vaccinium oxycoccos L. on acetic acid-induced colitis in mice

Posted: November 8, 2010
Authors: Popov SV, Markov PA, Nikitina IR, Petrishev S, Smirnov V, Ovodov YS
Journal: World J Gastroenterol 12(41):6646-51

Abstract: AIM: To study isolation and chemical characterization of pectin derived from the common cranberry Vaccinium oxycoccos L. (oxycoccusan OP) and the testing of its preventive effect on experimental colitis.

METHODS: Mice were administrated orally with OP two days prior to a rectal injection of 5% acetic acid and examined for colonic damage 24 h later. Colonic inflammation was characterized by macroscopical injury and enhanced levels of myeloperoxidase activity measured spectrophotometrically with o-phenylene diamine as the substrate. The mucus contents of the colon were determined by the Alcian blue dye binding method. Vascular permeability was estimated using 4% Evans blue passage after i.p. injection of 0.05 mol/L acetic acid.

RESULTS: In the mice treated with OP, colonic macroscopic scores (1.1+/-0.4 vs 2.7, P<0.01) and the total square area of damage (10+/-2 vs 21+/-7, P<0.01) were significantly reduced when compared with the vehicle-treated colitis group. OP was shown to decrease the tissue myeloperoxidase activity in colons (42+/-11 vs 112+/-40, P<0.01) and enhance the amount of mucus of colitis mice (0.9+/-0.1 vs 0.4+/-0.1, P<0.01). The level of colonic malondialdehyde was noted to decrease in OP-pretreated mice (3.6+/-0.7 vs 5.1+/-0.8, P<0.01). OP was found to decrease the inflammatory status of mice as was determined by reduction of vascular permeability (161+/-34 vs 241+/-21, P<0.01). Adhesion of peritoneal neutrophils and macrophages was also shown to decrease after administration of OP (141+/-50 vs 235+/-37, P<0.05).

CONCLUSION: Thus, a preventive effect of pectin from the common cranberry, namely oxycoccusan OP, on acetic acid-induced colitis in mice was detected. A reduction of neutrophil infiltration and antioxidant action may be implicated in the protective effect of oxycoccusan.

Role of cranberry juice on molecular-scale surface characteristics and adhesion behavior of Escherichia coli.

Posted: November 8, 2010
Authors: Liu Y, Black MA, Caron L, Camesano TA
Journal: Biotechnol Bioeng 93(2):297-305

Abstract: Cranberry juice has long been believed to benefit the prevention and treatment of urinary tract infections (UTIs). As the first step in the development of infection, bacterial adhesion is of great research interest, yet few studies have addressed molecular level adhesion in this context. P-fimbriated Escherichia coli play a major role in the development of a serious type of UTI, acute pyelonephritis. Experiments were conducted to investigate the molecular-scale effects of cranberry juice on two E. coli strains: HB101, which has no fimbriae, and the mutant HB101pDC1 which expresses P-fimbriae. Atomic force microscopy (AFM) was used to investigate both bacterial surface characteristics and adhesion forces between a probe surface (silicon nitride) and the bacteria, providing a direct evaluation of bacterial adhesion and interaction forces. Cranberry juice affected bacterial surface polymer and adhesion behavior after a short exposure period (<3 h). Cranberry juice affected the P-fimbriated bacteria by decreasing the adhesion forces between the bacterium and tip and by altering the conformation of the surface macromolecules on E. coli HB101pDC1. The equilibrium length of polymer (P-fimbriae) on this bacterium decreased from approximately 148 to approximately 48 nm upon being exposed to cranberry juice. Highly acidic conditions were not necessary for the prevention of bacterial adhesion, since neutralization of cranberry juice solutions to pH = 7.0 allowed us to observe differences in adhesion between the E. coli strains. Our results demonstrate molecular-level changes in the surfaces of P-fimbriated E. coli upon exposure to neutralized cranberry juice.

Urinary Excretion of (Epi)catechins in Rats Fed Different Berries or Berry Products

Posted: November 8, 2010
Authors: Khanal RC, Howard LR, Wilkes SE, Rogers TJ, Prior RL
Journal: J Agric Food Chem 58:11257-11264

Abstract: (Epi)catechins are associated with many health benefits in humans. However, their bioavailability, excretory pattern, and extent of conjugation in animals fed different sources or levels in the diet are not well documented. Two experiments were conducted to investigate the urinary excretion of (epi)catechins after feeding of different types of berries or different levels of the same berry source to rats. Experiment 1 investigated the effects of feeding a commercially available concentrated cranberry powder (CCP) at three different levels, 3.3, 6.6, and 33 g/kg of diet, whereas experiment 2 investigated the effect of feeding freeze-dried whole cranberry (CB), blueberry (BB), or black raspberry (BRB) powder at 50 g/kg of diet. Both experiments had an AIN-93-based control and a high-fructose diet (53-65% of the diet) to which was added three levels of CCP in experiment 1 and CB, BB, and BRB in experiment 2. (Epi)catechins were excreted as free and conjugated in both intact and methylated forms. Excretion of conjugated (epi)catechins was as high as 60% of the total consumed in some cases. A majority of both catechins and epicatechins excreted in the urine was in a methylated form. Excretion of epicatechins, including their methylated forms, ranged from 30 to 47% of the ingested amount, whereas that of catechins, including their methylated forms, ranged from 9 to 31%. Urinary excretion of (epi)catechins was dose dependent and increased with the amount of (epi)catechins present in the diet. On the basis of the excretory pattern of (epi)catechins in the urine, data suggested that the bioavailability of epicatechins may be higher than that of catechins and that (epi)catechins may be more available from blueberries compared to cranberries.

Urinary excretion of phenolic acids in rats fed cranberry

Posted: November 8, 2010
Authors: Prior RL, Rogers TR, Khanal RC, Wilkes SE, Wu X, Howard LR
Journal: J Agric Food Chem 58(7):3940-9

Abstract: Dietary flavonoids can be converted into phenolic acids by colonic microflora. Phenolic acids can then be absorbed into the circulation and may contribute to the health-promoting effects of the parent compounds. Phenolic acids can be further metabolized in other tissues via methylation and conjugation with glucuronide or sulfate. The objectives of this study were to identify and quantify the urinary excretion of 19 phenolic acids and their conjugates in rats fed three levels of a concentrated cranberry powder (3.3, 6.6, and 33 mg/kg of diet). The basic diet used was AIN93G diet containing very low amounts of any polyphenolic compounds. Of the phenolic acids studied, the amounts excreted varied by 4 orders of magnitude, with hippuric acid being excreted in the highest quantities. Amounts of 4-hydroxyphenylacetic acid (4HPAA), 3-hydroxyphenylacetic acid (3HPAA), 3-hydroxyphenylpropionic acid (3HPPA), and 4-hydroxycinnamic acid (4HCA) excreted were in the range of 18-33 microg/mg creatinine in animals fed the highest level of cranberry powder, whereas phenylacetic acid (PAA), gallic acid (GA), 3,4-dihydroxyphenylacetic acid (34HPAA), 3,4-dihydroxybenzoic acid (34HBA), 3,4-dihydroxycinnamic acid (34HCA), and 4-hydroxy-3-methoxycinnamic acid (FA) were excreted in the urine in concentrations of 0.1-2 microg/mg creatinine. As the amount of cranberry in the diet was increased, the amount of 4HPAA excreted decreased but the percentage of conjugated 4HPAA excreted increased (from 57 to 91%). For other phenolic acids analyzed, the percentage excreted in the conjugated form was approximately constant across levels of cranberry in the diet and ranged from 65 to 100% for the individual phenolic acids. Studies of bioactivity and health effects need to consider more than just the compound(s) in the food, because they can be metabolized to other lower molecular weight compounds, which in turn may also be methylated or conjugated in some form that may affect the perceived health effects.

Vaccinium macrocarpon: an interesting option for women with recurrent urinary tract infections and other health benefits

Posted: November 8, 2010
Authors: Perez-Lopez FR, Haya J and Chedraui P
Journal: J Obstet Gynaecol Res 35(4):630-9

Abstract: AIM: To review the scientific publications concerning the clinical use and mechanism of action of the North American cranberry (Vaccinium macrocarpon) for women with recurrent urinary tract infections (UTI) and other health conditions.

METHODS: This is a retrospective study of published information concerning Vaccinium macrocarpon retrieved from a PubMed and individual searches.

RESULTS: Urinary tract infections are very common in women, cause discomfort, and may aggravate other genitourinary conditions. The available scientific information supports a clinical benefit of Vaccinium macrocarpon in the prevention of recurrent UTI in women. There is a non-significant reduction of UTI associated with Vaccinium macrocarpon treatment during pregnancy. A group of proanthocyanidins (PAC) with A-type linkages have been isolated from Vaccinium macrocarpon which inhibit P-fimbriae synthesis and induce a bacterial deformation, on both antibiotic-susceptible and antibiotic-resistant uropathogenic Escherichia coli. It is plausible that cranberry PAC prevent bacteria from adhering to the uroepithelium of the bladder, thereby blocking the ability of E. coli to infect the urinary mucosa.

CONCLUSION: Cranberry treatment is a safe, well-tolerated supplement that does not have significant drug interactions. Although investigations are in the early stages, experimental and preclinical studies suggest that cranberry components may have other potential benefits, including anti-infective, anticancer and antioxidant effects, which may be considered as positive for different age-related conditions. In addition, cranberry components may induce positive cardiovascular and metabolic changes, and may improve neuropsychological activity. These effects warrant further clinical research to better place the role of cranberry products for women.

Risk factors for recurrent vulvovaginal candidiasis in women receiving maintenance antifungal therapy: results of a prospective cohort study.

Posted: November 7, 2010
Authors: Patel DA, Gillespie B, Sobel JD, Leaman D, Nyirjesy P, Weitz MV, Foxman B.
Journal: Am J Obstet Gynecol 190(3):644-53

Abstract: The purpose of this study was to examine risk factors for symptomatic vulvovaginal candidiasis episodes among women with recurrent vulvovaginal candidiasis (defined as >/=4 vulvovaginal candidiasis episodes in 1 year) who were receiving maintenance antifungal therapy.

STUDY DESIGN: A prospective study of 65 women aged >/=18 years with recurrent vulvovaginal candidiasis who attended vaginitis clinics in Detroit, Mich, and Philadelphia, Pa.

RESULTS: The 9-month risk of vulvovaginal candidiasis recurrence was 41.8%. Almost two fifths of the women reported activity limitations because of vulvovaginal candidiasis episodes, most or all of the time. Younger women and those women with a history of bacterial vaginosis were at increased risk of vulvovaginal candidiasis episodes. Behavioral factors that were associated significantly with increasing vulvovaginal candidiasis recurrence >/=2- fold included wearing pantyliners or pantyhose and consuming cranberry juice or acidophilus-containing products.

CONCLUSION: The use of pantyliners or pantyhose, consumption of cranberry juice or acidophil-containing products, a history of bacterial vaginosis, and age <40 years were positively associated with a symptomatic vulvovaginal candidiasis episode.

Urinary excretion of anthocyanins in humans after cranberry juice ingestion.

Posted: November 7, 2010
Authors: Ohnishi R, Ito H, Kasajima N, Kaneda M, Kariyama R, Kumon H, Hatano T, Yoshida T
Journal: Biosci Biotechnol Biochem 70(7):1681-7

Abstract: Cranberry, which is rich in polyphenols, including anthocyanins and proanthocyanidins, has been found to have various effects beneficial to human health, including prevention of urinary tract infections. These effects have been associated with polyphenols in the fruit. We investigated the excretion of anthocyanins in human urine after ingestion of cranberry juice. Eleven healthy volunteers consumed 200 ml of cranberry juice containing 650.8 microg total anthocyanins. Urine samples were collected within 24 h before and after consumption. Six of 12 anthocyanins identified in cranberry were quantified in human urine by HPLC coupled with electrospray ionization and tandem mass spectrometry (HPLC-ESI-MS-MS). Among these, peonidin 3-O-galactoside, the second most plentiful anthocyanin in the juice, was found most abundantly in urine within 24 h, corresponding to 41.5 nmol (56.1% of total anthocyanins). The urinary levels of anthocyanins reached a maximum between 3 and 6 h after ingestion, and the recovery of total anthocyanins in the urine over 24 h was estimated to be 5.0% of the amount consumed. This study found high absorption and excretion of cranberry anthocyanins in human urine.

Anti-angiogenic property of edible berries

Posted: November 6, 2010
Authors: Roy S, Khanna S, Alessio HM, Vider J, Bagchi D, Bagchi M, Sen CK
Journal: Free Radic Res 36(9):1023-31

Abstract: Recent studies show that edible berries may have potent chemopreventive properties. Anti-angiogenic approaches to prevent and treat cancer represent a priority area in investigative tumor biology. Vascular endothelial growth factor (VEGF) plays a crucial role for the vascularization of tumors. The vasculature in adult skin remains normally quiescent. However, skin retains the capacity for brisk initiation of angiogenesis during inflammatory skin diseases such as psoriasis and skin cancers. We sought to test the effects of multiple berry extracts on inducible VEGF expression by human HaCaT keratinocytes. Six berry extracts (wild blueberry, bilberry, cranberry, elderberry, raspberry seed, and strawberry) and a grape seed proanthocyanidin extract (GSPE) were studied. The extracts and uptake of their constituents by HaCaT were studied using a multi-channel HPLC-CoulArray approach. Antioxidant activity of the extracts was determined by ORAC. Cranberry, elderberry and raspberry seed samples were observed to possess comparable ORAC values. The antioxidant capacity of these samples was significantly lower than that of the other samples studied. The ORAC values of strawberry powder and GSPE were higher than cranberry, elderberry or raspberry seed but significantly lower than the other samples studied. Wild bilberry and blueberry extracts possessed the highest ORAC values. Each of the berry samples studied significantly inhibited both H2O2 as well as TNF alpha induced VEGF expression by the human keratinocytes. This effect was not shared by other antioxidants such as alpha-tocopherol or GSPE but was commonly shared by pure flavonoids. Matrigel assay using human dermal microvascular endothelial cells showed that edible berries impair angiogenesis.

Berry phenolics selectively inhibit the growth of intestinal pathogens

Posted: November 6, 2010
Authors: Puupponen-Pimiä R, Nohynek L, Hartmann-Schmidlin S, Kähkönen M, Heinonen M, Määttä-Riihinen K, Oksman-Caldentey KM.
Journal: J Appl Microbiol 98(4):991-1000

Abstract: AIMS: To investigate the effects of berries and berry phenolics on pathogenic intestinal bacteria and to identify single phenolic compounds being responsible for antimicrobial activity.

METHODS AND RESULTS: Antimicrobial activity of eight Nordic berries and their phenolic extracts and purified phenolic fractions were measured against eight selected human pathogens. Pathogenic bacterial strains, both Gram-positive and Gram-negative, were selectively inhibited by bioactive berry compounds. Cloudberry and raspberry were the best inhibitors, and Staphylococcus and Salmonella the most sensitive bacteria. Phenolic compounds, especially ellagitannins, were strong inhibitory compounds against Staphylococcus bacteria. Salmonella bacteria were only partly inhibited by the berry phenolics, and most of the inhibition seemed to originate from other compounds, such as organic acids. Listeria strains were not affected by berry compounds, with the exception of cranberry. Phenolic compounds affect the bacteria in different mechanisms.

CONCLUSIONS: Berries and their phenolics selectively inhibit the growth of human pathogenic bacteria.

SIGNIFICANCE AND IMPACT OF THE STUDY: Antimicrobial properties of berries could be utilized in functional foods. Furthermore these compounds would be of high interest for further evaluation of their properties as natural antimicrobial agents for food and pharmaceutical industry

Changes in plasma antioxidant capacity and oxidized low-density lipoprotein levels in men after short-term cranberry juice consumption.

Posted: November 6, 2010
Authors: Ruel G, Pomerleau S, Couture P, Lamarche B, Couillard C
Journal: Metabolism 54(7):856-61

Abstract: Low-density lipoprotein (LDL) oxidation is closely implicated in the development of atherosclerotic cardiovascular disease (CVD), and thus, reducing LDL susceptibility to oxidation with antoxidants could be of importance in CVD prevention. Flavonoids, polyphenolic compounds found in a large selection of fruits and vegetables, have been characterized as having a strong antioxidant potential, and intake of flavonoid-rich foods has been related to decreased morbidity and mortality from heart disease. The present study was therefore undertaken to investigate the effect of flavonoid-rich cranberry juice supplementation on plasma lipoprotein levels and LDL oxidation. For that purpose, 21 men (age +/- SD, 38 +/- 8 years) were enrolled in a 14-day intervention and instructed to drink cranberry juice 7 mL/kg body weight per day. Physical and metabolic measures including plasma lipid and oxidized LDL (OxLDL) concentrations as well as antioxidant capacity were performed before and after the intervention. At baseline, we found that plasma OxLDL levels were significantly associated with waist circumference ( r = 0.47, P = .0296) as well as plasma triglyceride ( r = 0.68, P = .0007) and apolipoprotein B ( r = 0.91, P < .0001) concentrations. The intervention led to a reduction in plasma OxLDL levels (-9.9% +/- 17.8%, P = .0131) and increase in antioxidant capacity (+6.5% +/- 10.3%, P = .0140). However, no relationship was found between both of these changes ( r = -.01, not significant). The intervention did not result in any improvement of plasma lipoprotein-lipid or inflammatory marker concentrations. Our results show that short-term cranberry juice supplementation is associated with significant increase in plasma antioxidant capacity and reduction in circulating OxLDL concentrations. Although the physiological relevance of our observations needs to be further examined, our study supports the potential role of antioxidant-rich foods in maintaining health and preventing CVD.

Cranberry flavonoids, atherosclerosis and cardiovascular health

Posted: November 6, 2010
Authors: Reed J
Journal: Crit Rev Food Sci Nutr 42(3 Suppl):301-16

Abstract: Atherosclerosis is the deposition of plaques containing cholesterol and lipids in arterial walls. Atherosclerosis causes cardiovascular disease that lead to heart attacks and stroke. Mortality from these diseases is the leading cause of death in the U.S. Atherogenisis starts with the uptake of oxidized LDL by endothelial macrophages, the accumulation of foam cells in the intima of the artery and the formation of fatty streaks. Research indicates that consumption of flavonoids in foods and beverages may decrease the risk of atherosclerosis. In vitro and in vivo experiments with flavonoids demonstrate that flavonoids are dietary antioxidants and inhibit LDL oxidation, inhibit platelet aggregation and adhesion, inhibit enzymes involved in lipid and lipoprotein metabolism that affect the immune response to oxidized LDL and their uptake by endothelial macrophages, may induce endothelium-dependent vassorelaxation, and may increase reverse cholesterol transport and decrease total and LDL cholesterol. Cranberries contain both hydroxycinnamic acids and flavonoids. The cranberry flavonoids belong to three groups: anthocyanins, flavonols, and proanthocyanidins. This article reviews the literature on the effects of flavonoids on atherosclerosis with an emphasis on the potential effects of the flavonols and proanthocyanidins in cranberries.

Cranberry juice and urinary tract infection.

Posted: November 6, 2010
Authors: Raz R, Chazan B, Dan M
Journal: Clin Infect Dis 38(10):1413-9

Abstract: Cranberries have long been the focus of interest for their beneficial effects in preventing urinary tract infections (UTIs). Cranberries contain 2 compounds with antiadherence properties that prevent fimbriated Escherichia coli from adhering to uroepithelial cells in the urinary tract. Approximately 1 dozen clinical trials have been performed testing the effects of cranberries on the urinary tract. However, these trials suffer from a number of limitations. Most importantly, the trials have used a wide variety of cranberry products, such as cranberry juice concentrate, cranberry juice cocktail, and cranberry capsules, and they have used different dosing regimens. Further research is required to clarify unanswered questions regarding the role of cranberries in protecting against UTI in general and in women with anatomical abnormalities in particular.

Effect of high-dose cranberry juice on the pharmacodynamics of warfarin in patients

Posted: November 6, 2010
Authors: Mellen CK, Ford M, Rindone JP
Journal: Br J Clin Pharmacol 70(1):139-42

Abstract: SUBJECT: Case reports suggest an association between cranberry juice and potentiation of warfarin. Studies using 240 ml of cranberry juice daily demonstrated no interaction. It is unknown if higher amounts of cranberry juice will interact with warfarin.

WHAT THIS STUDY ADDS: Cranberry juice at 240 ml twice daily does not alter the pharmacodynamics of warfarin.

AIM: To determine if high-dose cranberry juice (240 ml twice daily) alters the pharmacodynamic action of warfarin.

METHODS: Ten male patients taking stable doses of warfarin were given cranberry juice at 240 ml twice daily for 7 days. Prothrombin times were drawn at baseline and days 2, 6 and 8 after administration of the juice. Prothrombin times were averaged for each day and mean times were compared from each study day to baseline using repeated measures ANOVA.

RESULTS: There was no statistical difference between mean prothrombin time at baseline and any day tested during juice administration.

CONCLUSIONS: Cranberry juice (240 ml twice daily for 1 week) did not alter the pharmacodynamics of warfarin in patients.

Evidences of the cardioprotective potential of fruits: the case of cranberries.

Posted: November 6, 2010
Authors: Ruel G, Couillard C
Journal: Mol Nutr Food Res 51(6):692-701

Abstract: Eating a healthy balanced diet, is one of the most important and relevant ways to delay and prevent various health complications including cardiovascular disease (CVD). Among the nutritional factors that have been investigated in recent years, dietary fat intake may be the one that has been most targeted. However, there is also clear epidemiological evidence that increased fruits and vegetables intake can significantly reduce the risk of CVD, an effect that has been suggested to be resulting to a significant extent, from the high polyphenol content of these foods. Numerous polyphenolic compounds such as flavonoids have been identified as having strong antioxidant properties. Most interesting is the fact that, in addition to being one of the largest groups of antioxidant phytochemicals, flavonoids are also an integral part of the human diet as they are found in most fruits and vegetables. Cranberries are one of the most important sources of flavonoids that have a strong antioxidant and anti-inflammatory capacities. Thus, consumption of cranberries or their related products could be of importance not only in the maintenance of health but also in preventing CVD. The following review will present evidences supported for the most part by clinical observations that cranberries can exert potentially healthy effects for your heart.

Favourable impact of low-calorie cranberry juice consumption on plasma HDL-cholesterol concentrations in men

Posted: November 6, 2010
Authors: Ruel G, Pomerleau S, Couture P, Lemieux S, Lamarche B, Couillard C
Journal: Br J Nutr 96(2):357-64

Abstract: A low HDL-cholesterol concentration is an independent risk factor for CVD. Studies have suggested that flavonoid consumption may be cardioprotective, and a favourable impact on circulating HDL-cholesterol concentrations has been suggested to partially explain this association. The aim of the present study was to determine the effect of consuming increasing daily doses of low-calorie cranberry juice cocktail (CJC) on the plasma lipid profile of abdominally obese men. For that purpose, thirty men (mean age 51 (SD 10) years) consumed increasing doses of CJC during three successive periods of 4 weeks (125 ml/d, 250 ml/d, 500 ml/d). Before the study and after each phase, we measured changes in physical and metabolic variables. We noted a significant increase in plasma HDL-cholesterol concentration after the consumption of 250 ml CJC/d (+8.6+/-14.0% v. 0 ml CJC/d; P<0.01), an effect that plateaued during the last phase of the study (500 ml CJC/d: +8.1+/-10.0% v. 0 ml CJC/d; P<0.0001). Multivariate analyses revealed that changes in plasma apo A-I (R(2)=48%, P<0.0001) and triacylglycerol (R(2)=16%, P<0.005) concentrations were the only variables significantly contributing to the variation in plasma HDL-cholesterol concentration noted in response to the intervention. No variation was observed in total as well as in LDL and VLDL cholesterol. The present results show that daily CJC consumption is associated with an increase in plasma HDL-cholesterol concentrations in abdominally obese men. We hypothesise that polyphenolic compounds from cranberries may be responsible for this effect, supporting the notion that the consumption of flavonoid-rich foods can be cardioprotective.

Fighting infectious diseases with inhibitors of microbial adhesion to host tissues

Posted: November 6, 2010
Authors: Sharon N, Ofek I
Journal: Crit Rev Food Sci Nutr 42(3 Suppl):267-72

Abstract: The majority of infectious diseases are initiated by the adhesion of pathogenic organisms to the tissues of the host. In many cases this adhesion is mediated by lectins present on the surface of the infectious organism that bind to complementary carbohydrates on the surface of the host tissues. Soluble carbohydrates recognized by the bacterial lectins block the adhesion of the bacteria to animal cells in vitro. Moreover, such carbohydrates have been shown to protect against experimental infection by lectin-carrying bacteria of different mammals, such as mice, rabbits, calves, and monkeys. Agents other than carbohydrates also block adhesion, as demonstrated with cranberry juice as well as with low and high molecular weight preparations isolated from the juice. Both kinds of preparation inhibited the adhesion in vitro of Escherichia coli to different animal cells. In addition, the high molecular weight material acted similarly on the adhesion of Helicobacter pylori to human gasrointenstinal cells, and on the coaggregation of oral bacteria. Furthermore, in limited clinical studies regular drinking of cranberry juice had a significant preventive effect on bacteriuria, and the high molecular weight constituent of the juices was also effective in decreasing the salivary level of Streptococus mutans, the major cause of tooth decay. Because the inhibitors of adhesion examined are not bactericidal, the selection of resistant inhibitor strains is unlikely to occur. Together, these findings may lead to new therapeutic strategies that are in dire need because of the world-wide increase in antibiotic resistant bacteria.

Low-calorie cranberry juice supplementation reduces plasma oxidized LDL and cell adhesion molecule concentrations in men.

Posted: November 6, 2010
Authors: Ruel G, Pomerleau S, Couture P, Lemieux S, Lamarche B, Couillard C
Journal: Br J Nutr 99(2):352-9

Abstract: Elevated circulating concentrations of oxidized LDL (OxLDL) and cell adhesion molecules are considered to be relevant markers of oxidative stress and endothelial activation which are implicated in the development of CVD. On the other hand, it has been suggested that dietary flavonoid consumption may be cardioprotective through possible favourable impacts on LDL particle oxidation and endothelial activation. The present study was undertaken to determine the effect of the daily consumption of low-calorie cranberry juice cocktail on plasma OxLDL, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin concentrations in men. Thirty men (mean age 51 (sd 10) years) were recruited and asked to consume increasing daily doses of cranberry juice cocktail (125, 250 and 500 ml/d) over three successive periods of 4 weeks. Plasma OxLDL and adhesion molecule concentrations were measured by ELISA before and after each phase. We noted a significant decrease in plasma OxLDL concentrations following the intervention (P < 0.0001). We also found that plasma ICAM-1 (P < 0.0001) and VCAM-1 (P < 0.05) concentrations decreased significantly during the course of the study. In summary, the present results show that daily cranberry juice cocktail consumption is associated with decreases in plasma OxLDL, ICAM-1 and VCAM-1 concentrations in men.

Susceptibility of Helicobacter pylori isolates to the antiadhesion activity of a high-molecular-weight constituent of cranberry

Posted: November 6, 2010
Authors: Shmuely H, Burger O, Neeman I, Yahav J, Samra Z, Niv Y, Sharon N, Weiss E, Athamna A, Tabak M, Ofek I
Journal: Diagn Microbiol Infect Dis 50(4):231-5

Abstract: The sensitivity of a large number of antibiotic-resistant and nonresistant Helicobacter pylori isolates to the antiadhesion effect of a high-molecular-mass, nondialysable constituent of cranberry juice was tested. Confluent monolayers of gastric cell line in microtiter plate wells were exposed to bacterial suspensions prepared from 83 H. pylori isolates from antibiotic-treated and untreated patients in the presence and absence of the cranberry constituent. Urease assay was used to calculate the percentage of adhesion inhibition. In two thirds of the isolates, adhesion to the gastric cells was inhibited by 0.2 mg/mL of the nondialysable material. There was no relationship between the antiadhesion effect of the cranberry material and metronidazole resistance in isolates from either treated or untreated patients (N=35). Only 13 isolates (16%) were resistant to both the nondialysable material and metronidazole, and 30 (36%) were resistant to the nondialysable material alone. There was no cross-resistance to the nondialysable material and metronidazole. These data suggest that a combination of antibiotics and a cranberry preparation may improve H. pylori eradication.

The role of cranberry and probiotics in intestinal and urogenital tract health

Posted: November 6, 2010
Authors: Reid G
Journal: Crit Rev Food Sci Nutr 42(3 Suppl):293-300

Abstract: Several forces are driving an expanded use of nutraceuticals, particularly functional foods and probiotics, as instruments of the restoration and maintenance of well-being. These include consumer desire to use natural rather than pharmaceutical products, the mounting scientific evidence that shows efficacy of certain nutraceutical products, and the increasing cost and continued failure of drugs to cure or prevent disease. There is now a strong scientific basis for use of cranberries to reduce the risk of E. coli adhesion to bladder cells and the onset of urinary tract infection. There is also a mechanistic basis and clinical support for use of Lactobacillus strains such as L. rhamnosus GR-1 and L. fermentum RC-14 to colonize the intestine and vagina and reduce the risk of intestinal and urogenital infections. For such alternative approaches to be successful, scientific rigor must be backed by public education and physician acceptance. Given the emergence of virulent and multidrug-resistant pathogens, time is not on our side.

Total cranberry extract versus its phytochemical constituents: antiproliferative and synergistic effects against human tumor cell lines

Posted: November 6, 2010
Authors: Seeram NP, Adams LS, Hardy ML, Heber D
Journal: J Agric Food Chem 52(9):2512-7

Abstract: Cranberries (Vaccinium macrocarpon Ait.) are an excellent dietary source of phytochemicals that include flavonol glycosides, anthocyanins, proanthocyanidins (condensed tannins), and organic and phenolic acids. Using C-18 and Sephadex Lipophilic LH-20 column chromatography, HPLC, and tandem LC-ES/MS, the total cranberry extract (TCE) has been analyzed, quantified, and separated into fractions enriched in sugars, organic acids, total polyphenols, proanthocyanidins, and anthocyanins (39.4, 30.0, 10.6, 5.5, and 1.2% composition, respectively). Using a luminescent ATP cell viability assay, the antiproliferative effects of TCE (200 microg/mL) versus all fractions were evaluated against human oral (KB, CAL27), colon (HT-29, HCT116, SW480, SW620), and prostate (RWPE-1, RWPE-2, 22Rv1) cancer cell lines. The total polyphenol fraction was the most active fraction against all cell lines with 96.1 and 95% inhibition of KB and CAL27 oral cancer cells, respectively. For the colon cancer cells, the antiproliferative activity of this fraction was greater against HCT116 (92.1%) than against HT-29 (61.1%), SW480 (60%), and SW620 (63%). TCE and all fractions showed >/=50% antiproliferative activity against prostate cancer cells with total polyphenols being the most active fraction (RWPE-1, 95%; RWPE-2, 95%; 22Rv1, 99.6%). Cranberry sugars (78.8 microg/mL) did not inhibit the proliferation of any cancer cell lines. The enhanced antiproliferative activity of total polyphenols compared to TCE and its individual phytochemicals suggests synergistic or additive antiproliferative interactions of the anthocyanins, proanthocyanidins, and flavonol glycosides within the cranberry extract.

A high molecular mass cranberry constituent reduces mutans streptococci level in saliva and inhibits in vitro adhesion to hydroxyapatite

Posted: November 5, 2010
Authors: Weiss EI, Kozlovsky A, Steinberg D, Lev-Dor R, Bar Ness Greenstein R, Feldman M, Sharon N, Ofek I.
Journal: FEMS Microbiol Lett 232(1):89-92

Abstract: Previous investigations showed that a high molecular mass, non-dialyzable material (NDM) from cranberries inhibits the adhesion of a number of bacterial species and prevents the co-aggregation of many oral bacterial pairs. In the present study we determined the effect of mouthwash supplemented with NDM on oral hygiene. Following 6 weeks of daily usage of cranberry-containing mouthwash by an experimental group (n = 29), we found that salivary mutans streptococci count as well as the total bacterial count were reduced significantly (ANOVA, P < 0.01) compared with those of the control (n = 30) using placebo mouthwash. No change in the plaque and gingival indices was observed. In vitro, the cranberry constituent inhibited the adhesion of Streptococcus sobrinus to saliva-coated hydroxyapatite. The data suggest that the ability to reduce mutans streptococci counts in vivo is due to the anti-adhesion activity of the cranberry constituent.

Anti-Escherichia coli adhesin activity of cranberry and blueberry juices.

Posted: November 5, 2010
Authors: Ofek I, Goldhar J, Zafriri D, Lis H, Adar R, Sharon N.
Journal: N Engl J Med 324(22):1599

Abstract: No abstract - The high-molecular-weight inhibitor of adhesin was partially purified from cranberry juice by gel-filtration chromatography. The product was heat-stable, resistant to trypsin, and nondialysable, and it inhibited the MR adhesin of al 20 urinary isolates tested in concentrations of 12 to 25 µg per milliliter. On the basis of these results, together with those of earlier studies, we suggest that the antiadhesive agents in juices from vaccinium berries may act in the gut (the source of most uropathogens), in the bladder, or both by preventing colonization of these sites.

Antioxidant activities and antitumor screening of extracts from cranberry fruit (Vaccinium macrocarpon)

Posted: November 5, 2010
Authors: Yan X, Murphy BT, Hammond GB, Vinson JA, Neto CC
Journal: J Agric Food Chem 50(21):5844-9

Abstract: Polyphenolic compounds in cranberries have been investigated to determine their role in protection against cardiovascular disease and some cancers. Extracts of whole fruit were assayed for radical-scavenging activity and tumor growth inhibition using seven tumor cell lines. Selective inhibition of K562 and HT-29 cells was observed from a methanolic extract in the range of 16-125 microg/mL. Radical-scavenging activity was greatest in an extract composed primarily of flavonol glycosides. Seven flavonol glycosides were isolated and purified from whole fruit for further evaluation; the anthocyanin cyanidin 3-galactoside was also purified for comparison with the flavonoids. Three flavonol monoglycosides were newly identified by (13)C NMR as myricetin 3-alpha-arabinofuranoside, quercetin 3-xyloside, and 3-methoxyquercetin 3-beta-galactoside (isorhamnetin); the other four isolated were the previously identified myricetin 3-beta-galactoside, quercetin 3-beta-galactoside, quercetin 3-alpha-arabinofuranoside, and quercetin 3-alpha-rhamnopyranoside. These compounds were evaluated for 1,1-diphenyl-2-picrylhydrazyl radical-scavenging activity and ability to inhibit low-density lipoprotein oxidation in vitro. Most of the flavonol glycosides showed antioxidant activity comparable or superior to that of vitamin E; cyanidin 3-galactoside showed activity superior to that of the flavonoids as well as vitamin E or Trolox in both antioxidant assays.

Antioxidant and antiproliferative activities of common fruits.

Posted: November 5, 2010
Authors: Sun J, Chu YF, Wu X, Liu RH
Journal: J Agric Food Chem 50(25):7449-54

Abstract: Consumption of fruits and vegetables has been associated with reduced risk of chronic diseases such as cardiovascular disease and cancer. Phytochemicals, especially phenolics, in fruits and vegetables are suggested to be the major bioactive compounds for the health benefits. However, the phenolic contents and their antioxidant activities in fruits and vegetables were underestimated in the literature, because bound phenolics were not included. This study was designed to investigate the profiles of total phenolics, including both soluble free and bound forms in common fruits, by applying solvent extraction, base digestion, and solid-phase extraction methods. Cranberry had the highest total phenolic content, followed by apple, red grape, strawberry, pineapple, banana, peach, lemon, orange, pear, and grapefruit. Total antioxidant activity was measured using the TOSC assay. Cranberry had the highest total antioxidant activity (177.0 +/- 4.3 micromol of vitamin C equiv/g of fruit), followed by apple, red grape, strawberry, peach, lemon, pear, banana, orange, grapefruit, and pineapple. Antiproliferation activities were also studied in vitro using HepG(2) human liver-cancer cells, and cranberry showed the highest inhibitory effect with an EC(50) of 14.5 +/- 0.5 mg/mL, followed by lemon, apple, strawberry, red grape, banana, grapefruit, and peach. A bioactivity index (BI) for dietary cancer prevention is proposed to provide a new alternative biomarker for future epidemiological studies in dietary cancer prevention and health promotion.

Cranberry high molecular weight constituents promote Streptococcus sobrinus desorption from artificial biofilm

Posted: November 5, 2010
Authors: Steinberg D, Feldman M, Ofek I, Weiss EI
Journal: Int J Antimicrob Agents 5(3):247-51

Abstract: Dental biofilm harbouring oral bacteria is highly correlated with the progression of dental diseases. Disruption of biofilm formation via anti-adhesion agents is an alternative means to the antibacterial approach. Previous studies have shown that high molecular weight non-dialysable material (NDM) derived from cranberry juice inhibits the adhesion of Escherichia coli and the coaggregation of a variety of oral bacteria. In addition, it inhibits the formation of glucans and fructans synthesised by GTF and FTF. In the present study, we examined the anti-adhesion effect of NDM on S. sobrinus. NDM promoted desorption of S. sobrinus from biofilm in the presence and absence of extracellular glucans and fructans, although the effect was more pronounced in the absence of these polysaccharides. Precoating of the bacteria with NDM reduced their ability to form biofilm. Our results indicate that NDM could be exploited as an anti-biofilm agent.

Cranberry juice constituents affect influenza virus adhesion and infectivity

Posted: November 5, 2010
Authors: Weiss EI, Houri-Haddad Y, Greenbaum E, Hochman N, Ofek I, Zakay-Rones Z.
Journal: Antiviral Res 66(1):9-12

Abstract: Cranberry juice contains high molecular weight materials (NDM) that inhibit bacterial adhesion to host cells as well as the co-aggregation of many oral bacteria. Because of its broad-spectrum activity, we investigated NDM's potential for inhibiting influenza virus adhesion to cells, and subsequent infectivity. Hemagglutination (HA) of red blood cells (RBC) caused by representatives of both influenza virus A subtypes (H1N1)and H3N2) and the B type was inhibited by NDM at concentrations of 125 microg/ml or lower, which is at least 20-fold lower than that usually found in cranberry juice. A dose-response effect of NDM on HA was demonstrated. The infectivity of the A and B types was significantly reduced by preincubation with NDM (250 microg/ml), as reflected by the lack of cytopathic effect on Madine-Darby canine kidney (MDCK) cells and the lack of HA activity in the media of infected cells. The effect of NDM was also tested after A or B type viruses were allowed to adsorb to and penetrate the cells. Various levels of reduction in virus tissue culture infective dose TCID50 were observed. The effect was most pronounced when NDM was added several times to the infected MDCK cells. Our cumulative findings indicate that the inhibitory effect of NDM on influenza virus adhesion and infectivity may have a therapeutic potential.

Cranberry proanthocyanidins and the maintenance of urinary tract health

Posted: November 5, 2010
Authors: Howell AB
Journal: Crit Rev Food Sci Nutr 42(3 Suppl):273-8

Abstract: One of the major health benefits attributed to the ingestion of cranberry juice is the maintenance of urinary tract health. Traditionally, the juice was thought to cause acidification of the urine resulting in a bacteriostatic effect. However, recent research has demonstrated that a bacterial antiadhesion mechanism is responsible. Proanthocyanidins with unique molecular structures have been isolated from cranberry fruit that exhibit potent bacterial antiadhesion activity. Little is known about the bioavailability and structure-activity relationships of cranberry proanthocyanidins. Data on how certain structural features of the molecules can influence bioactivity and bioavailability are reviewed.

Effect of a high-molecular-weight component of cranberry on constituents of dental biofilm

Posted: November 5, 2010
Authors: Steinberg D, Feldman M, Ofek I, Weiss EI
Journal: J Antimicrob Chemother 54(1):86-9

Abstract: BACKGROUND: Previous studies have shown that high molecular-weight non-dialysable material derived from cranberry juice (NDM) inhibits co-aggregation of a variety of oral bacteria.

OBJECTIVES: In the present study, we examined the effect of NDM on several constituents of the dental biofilm, glucosyltransferase (GTF) and fructosyltransferase (FTF), as well as on the adhesion of Streptococcus sobrinus.

RESULTS: The activity of immobilized and soluble GTF and FTF was inhibited by NDM (P > 0.05). NDM also inhibited adhesion of S. sobrinus to hydroxyapatite (P < 0.05).

CONCLUSIONS: Our results indicate that NDM may affect biofilm formation. One of the proposed mechanisms is via inhibition of extracellular polysaccharide synthesis, which promote the sucrose-dependent adhesion of oral bacteria as S. sobrinus.

Effect of cranberry extract on bacteriuria and pyuria in persons with neurogenic bladder secondary to spinal cord injury.

Posted: November 5, 2010
Authors: Waites KB, Canupp KC, Armstrong S, DeVivo MJ
Journal: J Spinal Cord Med 27(1):35-40

Abstract: OBJECTIVE: To determine whether antibacterial effects of cranberry extract will reduce or eliminate bacteriuria and pyuria in persons with spinal cord injury (SCI).

DESIGN: Randomized, double-blind, placebo-controlled study.

PARTICIPANTS: Participants were people with SCI residing in the community who were 1 year or longer postinjury with neurogenic bladder managed by intermittent catheterization or external collection device and a baseline urine culture demonstrating at least 10(5) colonies per milliliter of bacteria.

METHODS: Each participant ingested 2 g of concentrated cranberry juice or placebo in capsule form daily for 6 months. Baseline urinalysis and cultures were performed at the time of the initial clinic visit and monthly for 6 months. Microbiologic data were evaluated using analysis of variance with repeated measures.

RESULTS: Twenty-six persons received cranberry extract and 22 persons received placebo. There were no differences or trends detected between participants and controls with respect to number of urine specimens with bacterial counts of at least 10(4) colonies per milliliter, types and numbers of different bacterial species, numbers of urinary leukocytes, urinary pH, or episodes of symptomatic urinary tract infection.

CONCLUSION: Cranberry extract taken in capsule form did not reduce bacteriuria and pyuria in persons with SCI and cannot be recommended as a means to treat these conditions.

Effect of ingesting cranberry juice on bacterial growth in urine.

Posted: November 5, 2010
Authors: Tong H, Heong S and Chang S
Journal: Am J Health Syst Pharm 63(15):1417-9

Abstract: No abstract - Introduction: Cranberry juice has been shown to have a significant effect in preventing urinary tract infections (UTIs) in a number of clinical trials. This property of cranberry juice has been attributed to an ability to inhibit bacterial adherence to cells and possibly its urine acidification effects. However, cranberry juice’s antibacterial activity in urine remains unknown. Although a preliminary study by Lee et al. found that concentrated cranberry juice has some antibacterial activity, cranberry juice was studied, not the resultant urine samples. Therefore, our study investigated whether cranberry juice has antibacterial effects in urine. We excluded acidification as a possible antibacterial factor.

Effects of cranberry juice on nifedipine pharmacokinetics in rats

Posted: November 5, 2010
Authors: Uesawa Y, Mohri K
Journal: J Pharm Pharmacol 58(8):1067-72

Abstract: Little information is available about drug interactions with cranberry juice (CJ). Using microsomes from the human liver and rat small intestine, this study was designed to determine whether CJ could inhibit CYP3A-mediated nifedipine (NFP) oxidase activity; it showed that CJ was a potent inhibitor of human and rat CYP3A. Preincubation with 10% vol/vol of CJ and 1 mM NADPH for 10 min resulted in significant inhibition of the NFP oxidation activity of human and rat CYP3A (18.2 and 12.6% decreases, respectively, compared with preincubation experiments without NADPH). In addition, the pharmacokinetic interaction between CJ and NFP in vivo was confirmed in rats. In comparison with a control group, the area under the concentration-time curve (AUC) of NFP was approximately 1.6-fold higher when CJ (2 mL) was injected intraduodenally 30 min before the intraduodenal administration of NFP (30 mg kg(-1)). However, the mean residence time, the volume of distribution and the elimination rate constant were not changed significantly. These data suggest that CJ component(s) inhibit the function of enteric CYP3A. In conclusion, it was found that CJ inhibits the CYP3A-mediated metabolism of NFP in both rats and humans. Furthermore, CJ alters NFP pharmacokinetics in rats.

Enhancing health benefits of berries through phenolic antioxidant enrichment: focus on cranberry.`

Posted: November 5, 2010
Authors: Vattem DA, Ghaedian R, Shetty K
Journal: Asia Pac J Clin Nutr 14(2):120-30

Abstract: Emerging epidemiological evidence is increasingly pointing to the beneficial effects of fruits and vegetables in managing chronic and infectious diseases. These beneficial effects are now suggested to be due to the constituent phenolic phytochemicals having antioxidant activity. Cranberry like other fruits is also rich in phenolic phytochemicals such as phenolic acids, flavonoids and ellagic acid. Consumption of cranberry has been historically been linked to lower incidences of urinary tract infections and has now been shown to have a capacity to inhibit peptic ulcer-associated bacterium, Helicobacter pylori. Isolated compounds from cranberry have also been shown to reduce the risk of cardiovascular diseases. Recent evidence suggests the ability of phytochemical components in whole foods in being more effective in protectively supporting human health than compared to isolated individual phenolic phytochemicals. This implies that the profile of phenolic phytochemicals determines the functionality of the whole food as a result of synergistic interaction of constituent phenolic phytochemicals. Solid state bioprocessing using food grade fungi common in Asian food cultures as well as cranberry phenolic synergies through the addition of functional biphenyls such as ellagic acid and rosmarinic acid along with processed fruit extracts have helped to advance these concepts. These strategies could be further explored to enrich cranberry and cranberry products with functional phytochemicals and further improve their functionality for enhancing health benefits.

GC-MS determination of flavonoids and phenolic and benzoic acids in human plasma after consumption of cranberry juice

Posted: November 5, 2010
Authors: Zhang K, Zuo Y
Journal: J Agric Food Chem 52(2):222-7

Abstract: A GC-MS method was developed for the determination of various flavonoids and phenolic and benzoic acids in human plasma. The procedure involved the extraction of flavonoids and phenolic and benzoic acids with ethyl acetate, followed by the derivatization of the phenolic and benzoic compounds with BSTFA (N,O-bis(trimethylsilyl) trifluoroacetamide) + TMCS (trimethylchlorosilane) reagent. The trimethylsilyl derivatives formed were separated and quantitated using GC-MS. Twenty flavonoids and phenolic and benzoic compounds have been well separated in the spiked human plasma without any interference. The average recovery was 79.3%. Several phenolic acids such as o-hydroxybenzoic, p-hydroxyphenylacetic, 2,3-dihydroxybenzoic, 2,4-dihydroxybenzoic, ferulic, sinapic, and benzoic acid were identified and quantified in human plasma after consumption of a cranberry juice. This developed method provides a simple, specific, and sensitive technique for the simultaneous determination of flavonoids and phenolic and benzoic acids in human plasma and is suitable for bioavailability and pharmacokinetic studies.

Inhibition of uropathogenic Escherichia coli by cranberry juice: a new antiadherence assay

Posted: November 5, 2010
Authors: Turner A, Chen SN, Joike MK, Pendland SL, Pauli GF, Farnsworth NR
Journal: J Agric Food Chem 53(23):8940-7

Abstract: A combination of microplate technology and turbidity assessment for testing the adherence of P-fimbriated Escherichia coli to human uroepithelial cell line T24, validated with the addition of the known inhibitor 4-O-alpha-D-galactopyranosyl-alpha-D-galactopyranose (galabiose), resulted in a high-throughput, biologically relevant assessment of cranberry (Vaccinium macrocarpon). P-fimbriated ATCC E. coli strains 25922, 29194, and 49161 were inhibited by galabiose. ATCC 29194, a representative urine isolate containing the papGII allele (Class II fimbrial adhesin) and demonstrating the most significant inhibition in the presence of galabiose, was chosen for further testing. In this assay, a low-polarity fraction of cranberry juice cocktail demonstrated dose-dependent inhibition of E. coli adherence. Reported here, for the first time in V. macrocarpon, are 1-O-methylgalactose, prunin, and phlorizin, identified in an active fraction of cranberry juice concentrate. This in vitro assay will be useful for the standardization of cranberry dietary supplements and is currently being used for bioassay-guided fractionation of cranberry juice concentrate.

Plasma matrix metalloproteinase (MMP)-9 levels are reduced following low-calorie cranberry juice supplementation in men

Posted: November 5, 2010
Authors: Ruel G, Pomerleau S, Couture P, Lemieux S, Lamarche B and Couillard C
Journal: J Am Coll Nutr 28(6):694-701

Abstract: OBJECTIVE: Matrix metalloproteinase (MMP)-9, also known as gelatinase B, is implicated in the development of hypertension and atherosclerotic plaque vulnerability to rupture, an important step in the etiology of cardiovascular diseases. Studies have suggested that flavonoid consumption may be cardioprotective, and its favorable impact on circulating MMP-9 concentrations could partly explain this association. The aim of the present study was to determine the effect of consuming increasing daily doses of low-calorie cranberry juice cocktail (CJC) on plasma MMP-9 concentrations of abdominally obese men.
METHODS: Thirty men (mean age +/- SD: 51 +/- 10 years) consumed increasing doses of CJC during 3 successive periods of 4 weeks (weeks 1-4: 125 ml/day, weeks 5-8: 250 ml/day, and weeks 9-12: 500 ml/day). Before the study and after each phase, a series of physical and metabolic variables were measured, including MMP-9.
RESULTS: We found that CJC supplementation significantly decreased plasma MMP-9 concentrations (mean +/- SEM: -36% +/- 9%, p < 0.0005; week 12 vs. baseline) while baseline plasma MMP-9 concentrations strongly correlated with the changes noted over the entire intervention (r = -0.71, p < 0.0001). We also show that the reduction in plasma MMP-9 levels was associated with a change in plasma nitrites/nitrates (NOx) concentration over the entire intervention (r = -0.38, p < 0.05; week 12 vs. baseline). Significant correlations were also noted between changes in plasma MMP-9 levels and those of systolic (r = 0.39, p < 0.05) and diastolic (r = 0.60, p < 0.001) blood pressure during the course of the study (week 12 vs. baseline).
CONCLUSIONS: Our results show that daily CJC consumption is associated with a decrease in plasma MMP-9 concentrations in abdominally obese men. We hypothesize that polyphenolic compounds from cranberries may be responsible for this effect, supporting the notion that the consumption of flavonoid-rich foods can exert cardioprotective effects.

Prevention of catheter-associated urinary tract infection.

Posted: November 5, 2010
Authors: Trautner BW, Hull RA, Darouiche RO
Journal: Curr Opin Infect Dis 18(1):37-41

Abstract: PURPOSE OF REVIEW: The underlying cause of catheter-associated urinary tract infection is biofilm formation by uropathogens on the urinary catheter. Biofilm is a relatively new concept in medicine, and current measures to prevent biofilm formation are inadequate. Considerable work is being done in this area, but little clinical progress has been made. The purpose of this review is to analyze recent publications concerning prevention of catheter-associated urinary tract infection.

RECENT FINDINGS: Several recent studies have elucidated aspects of biofilm formation in catheter-associated urinary tract infection. Other researchers are working on methods to disrupt biofilm formation on catheter surfaces. At the same time, the magnitude of the problem of catheter-associated urinary tract infection has increased awareness of the effectiveness of basic infection control measures. A modern approach to infection control may include computerized ordering systems that minimize unnecessary days of catheterization. Finally, consumption of cranberry juice products and bacterial interference are two novel approaches to urinary tract infection prevention.

SUMMARY: Biofilm-disrupting strategies offer promise for the future but have little immediate applicability. Implementation of infection control measures to improve catheter function and remove unnecessary catheters can be done at the present time. In general, prevention of catheter-associated urinary tract infection remains an elusive goal. More basic research at the level of pathogenesis is needed so that novel strategies can be designed.

Anti-Porphyromonas gingivalis and anti-inflammatory activities of A-type cranberry proanthocyanidins.

Posted: November 4, 2010
Authors: La VD, Howell AB, Grenier D
Journal: Antimicrob Agents Chemother 54(5):1778-84

Abstract: A-type cranberry proanthocyanidins (AC-PACs) have recently been reported to be beneficial for human health, especially urinary tract health. The effect of these proanthocyanidins on periodontitis, a destructive disease of tooth-supporting tissues, needs to be investigated. The purpose of this study was to investigate the effects of AC-PACs on various virulence determinants of Porphyromonas gingivalis as well as on the inflammatory response of oral epithelial cells stimulated by this periodontopathogen. We examined the effects of AC-PACs on P. gingivalis growth and biofilm formation, adherence to human oral epithelial cells and protein-coated surfaces, collagenase activity, and invasiveness. We also tested the ability of AC-PACs to modulate the P. gingivalis-induced inflammatory response by human oral epithelial cells. Our results showed that while AC-PACs neutralized all the virulence properties of P. gingivalis in a dose-dependent fashion, they did not interfere with growth. They also inhibited the secretion of interleukin-8 (IL-8) and chemokine (C-C motif) ligand 5 (CCL5) but did not affect the secretion of IL-6 by epithelial cells stimulated with P. gingivalis. This anti-inflammatory effect was associated with reduced activation of the nuclear factor-kappaB (NF-kappaB) p65 pathway. AC-PACs may be potentially valuable bioactive molecules for the development of new strategies to treat and prevent P. gingivalis-associated periodontal diseases.

Biosafety, antioxidant status, and metabolites in urine after consumption of dried cranberry juice in healthy women: a pilot double-blind placebo-controlled trial.

Posted: November 4, 2010
Authors: Valentova K, Stejskal D, Bednar P, Vostalova J, Cíhalík C, Vecerova R, Koukalova D, Kolar M, Reichenbach R, Sknouril L, Ulrichova J, Simanek V
Journal: J Agric Food Chem 55(8):3217-24

Abstract: This study assessed the effect of an 8 week consumption of dried cranberry juice (DCJ) on 65 healthy young women. Basic biochemical and hematological parameters, antioxidant status, presence of metabolites in urine, and urine ex vivo antiadherence activity were determined throughout the trial. A 400 mg amount of DCJ/day had no influence on any parameter tested. A 1200 mg amount of DCJ/day resulted in a statistically significant decrease in serum levels of advanced oxidation protein products. This specific protective effect against oxidative damage of proteins is described here for the first time. Urine samples had an inhibitory effect on the adhesion of uropathogenic Escherichia coli strains, but no increase in urine acidity was noted. Hippuric acid, isomers of salicyluric and dihydroxybenzoic acids, and quercetin glucuronide were identified as the main metabolites. In conclusion, cranberry fruits are effective not only in the prevention of urinary tract infection but also for the prevention of oxidative stress.

Complementary, holistic, and integrative medicine: cranberry.

Posted: November 4, 2010
Authors: Shamseer L, Vohra S
Journal: Pediatr Rev 28 (8):e43-5

Abstract: No abstract - Introduction: Cranberry is among the most commonly used natural health products in North America. Commercial cranberry products commonly are derived from the Vaccinium oxycoccos and V macrocarpon species, which are cultivated widely across the Northern hemisphere. Seventy percent of the cranberry crop in North America is controlled by a single manufacturer. Historically, cranberry fruits and leaves have been used for wound dressings, urinary disorders, diabetes, blood poisoning, diarrhea, and liver problems. More recently, cranberry has been used to prevent urinary tract infections (UTIs) and dental plaque. The scientific evidence regarding medicinal uses of cranberry in pediatric populations is presented in this article.

Cranberries and cranberry products: powerful in vitro, ex vivo, and in vivo sources of antioxidants.

Posted: November 4, 2010
Authors: Vinson JA, Bose P, Proch J, Al Kharrat H, Samman N
Journal: J Agric Food Chem 56(14):5884-91

Abstract: Cranberry products and especially cranberry juice (CJ) have been consumed for health reasons primarily due to their effect on urinary tract infections. We investigated the quantity of both free and total (after hydrolysis) phenolic antioxidants in cranberry products using the Folin assay. The order of amount of total polyphenols in cranberry foods on a fresh weight basis was as follows: dried > frozen > sauce > jellied sauce. On a serving size basis for all cranberry products, the order was as follows: frozen > 100% juice > dried > 27% juice > sauce > jellied sauce. High fructose corn syrup (HFCS) is a major source of sugar consumption in the U.S. and contains both glucose and fructose, potential mediators of oxidative stress. We investigated the effect of the consumption of HFCS and ascorbate with CJ antioxidants or without CJ (control) given to 10 normal individuals after an overnight fast. Plasma antioxidant capacity, glucose, triglycerides, and ascorbate were measured 6 times over 7 h after the consumption of a single 240 mL serving of the two different beverages. The control HFCS caused a slight decrease in plasma antioxidant capacity at all time points and thus an oxidative stress in spite of the presence of ascorbate. CJ produced an increase in plasma antioxidant capacity that was significantly greater than control HFCS at all time points. Postprandial triglycerides, due to fructose in the beverages, were mainly responsible for the oxidative stress and were significantly correlated with the oxidative stress as measured by the antioxidant capacity. Cranberries are an excellent source of high quality antioxidants and should be examined in human supplementation studies.

Cranberries for preventing urinary tract infections

Posted: November 4, 2010
Authors: Jepson RG, Craig JC
Journal: Cochrane Database Syst Rev (1):CD001321

Abstract: BACKGROUND: Cranberries have been used widely for several decades for the prevention and treatment of urinary tract infections (UTIs).

OBJECTIVES: To assess the effectiveness of cranberry products in preventing UTIs in susceptible populations.

SEARCH STRATEGY: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL in The Cochrane Library) and the Internet. We contacted companies involved with the promotion and distribution of cranberry preparations and checked reference lists of review articles and relevant studies. Date of last search: January 2007.

SELECTION CRITERIA: All randomised controlled trials (RCTs) or quasi-RCTs of cranberry products for the prevention of UTIs in all populations.

DATA COLLECTION AND ANALYSIS: Two authors independently assessed and extracted information. Information was collected on methods, participants, interventions and outcomes (UTIs - symptomatic and asymptomatic, side effects, adherence to therapy). Relative risk (RR) were calculated where appropriate, otherwise a narrative synthesis was undertaken. Quality was assessed using the Cochrane criteria.

MAIN RESULTS: Ten studies (n = 1049, five cross-over, five parallel group) were included. Cranberry/cranberry-lingonberry juice versus placebo, juice or water was evaluated in seven studies, and cranberries tablets versus placebo in four studies (one study evaluated both juice and tablets). Cranberry products significantly reduced the incidence of UTIs at 12 months (RR 0.65, 95% CI 0.46 to 0.90) compared with placebo/control. Cranberry products were more effective reducing the incidence of UTIs in women with recurrent UTIs, than elderly men and women or people requiring catheterisation. Six studies were not included in the meta-analyses due to methodological issues or lack of available data. However, only one reported a significant result for the outcome of symptomatic UTIs. Side effects were common in all studies, and dropouts/withdrawals in several of the studies were high.

AUTHORS' CONCLUSIONS: There is some evidence that cranberry juice may decrease the number of symptomatic UTIs over a 12 month period, particularly for women with recurrent UTIs. It's effectiveness for other groups is less certain. The large number of dropouts/withdrawals indicates that cranberry juice may not be acceptable over long periods of time. It is not clear what is the optimum dosage or method of administration (e.g. juice, tablets or capsules). Further properly designed studies with relevant outcomes are needed.

Cranberry (Vaccinium macrocarpon) protects against doxorubicin-induced cardiotoxicity in rats

Posted: November 4, 2010
Authors: Elberry AA, Abdel-Naim AB, Abdel-Sattar EA, Nagy AA, Mosli HA, Mohamadin AM, Ashour OM.
Journal: Food Chem Toxicol 48(5):1178-84

Abstract: Doxorubicin (DOX) is a widely used cancer chemotherapeutic agent. However, it generates free oxygen radicals that result in serious dose-limiting cardiotoxicity. Supplementations with berries were proven effective in reducing oxidative stress associated with several ailments. The aim of the current study was to investigate the potential protective effect of cranberry extract (CRAN) against DOX-induced cardiotoxicity in rats. CRAN was given orally to rats (100mg/kg/day for 10 consecutive days) and DOX (15mg/kg; i.p.) was administered on the seventh day. CRAN protected against DOX-induced increased mortality and ECG changes. It significantly inhibited DOX-provoked glutathione (GSH) depletion and accumulation of oxidized glutathione (GSSG), malondialdehyde (MDA), and protein carbonyls in cardiac tissues. The reductions of cardiac activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione reductase (GR) were significantly mitigated. Elevation of cardiac myeloperoxidase (MPO) activity in response to DOX treatment was significantly hampered. Pretreatment of CRAN significantly guarded against DOX-induced rise of serum lactate dehydrogenase (LDH), creatine phosphokinase (CK), creatine kinase-MB (CK-MB) as well as troponin I level. CRAN alleviated histopathological changes in rats' hearts treated with DOX. In conclusion, CRAN protects against DOX-induced cardiotoxicity in rats. This can be attributed, at least in part, to CRAN's antioxidant activity.

Cranberry and urinary tract infections

Posted: November 4, 2010
Authors: Guay DR
Journal: Drugs 69(7):775-807

Abstract: Urinary tract infection (UTI) refers to the presence of clinical signs and symptoms arising from the genitourinary tract plus the presence of one or more micro-organisms in the urine exceeding a threshold value for significance (ranges from 102 to 103 colony-forming units/mL). Infections are localized to the bladder (cystitis), renal parenchyma (pyelonephritis) or prostate (acute or chronic bacterial prostatitis). Single UTI episodes are very common, especially in adult women where there is a 50-fold predominance compared with adult men. In addition, recurrent UTIs are also common, occurring in up to one-third of women after first-episode UTIs. Recurrences requiring intervention are usually defined as two or more episodes over 6 months or three or more episodes over 1 year (this definition applies only to young women with acute uncomplicated UTIs). A cornerstone of prevention of UTI recurrence has been the use of low-dose once-daily or post-coital antimicrobials; however, much interest has surrounded non-antimicrobial-based approaches undergoing investigation such as use of probiotics, vaccines, oligosaccharide inhibitors of bacterial adherence and colonization, and bacterial interference with immunoreactive extracts of Escherichia coli. Local (intravaginal) estrogen therapy has had mixed results to date. Cranberry products in a variety of formulations have also undergone extensive evaluation over several decades in the management of UTIs. At present, there is no evidence that cranberry can be used to treat UTIs. Hence, the focus has been on its use as a preventative strategy. Cranberry has been effective in vitro and in vivo in animals for the prevention of UTI. Cranberry appears to work by inhibiting the adhesion of type I and P-fimbriated uropathogens (e.g. uropathogenic E. coli) to the uroepithelium, thus impairing colonization and subsequent infection. The isolation of the component(s) of cranberry with this activity has been a daunting task, considering the hundreds of compounds found in the fruit and its juice derivatives. Reasonable evidence suggests that the anthocyanidin/proanthocyanidin moieties are potent antiadhesion compounds. However, problems still exist with standardization of cranberry products, which makes it extremely difficult to compare products or extrapolate results. Unfortunately, most clinical trials have had design deficiencies and none have evaluated specific key cranberry-derived compounds considered likely to be active moieties (e.g. proanthocyanidins). In general, the preventive efficacy of cranberry has been variable and modest at best. Meta-analyses have established that recurrence rates over 1 year are reduced approximately 35% in young to middle-aged women. The efficacy of cranberry in other groups (i.e. elderly, paediatric patients, those with neurogenic bladder, those with chronic indwelling urinary catheters) is questionable. Withdrawal rates have been quite high (up to 55%), suggesting that these products may not be acceptable over long periods. Adverse events include gastrointestinal intolerance, weight gain (due to the excessive calorie load) and drug-cranberry interactions (due to the inhibitory effect of flavonoids on cytochrome P450-mediated drug metabolism). The findings of the Cochrane Collaboration support the potential use of cranberry products in the prophylaxis of recurrent UTIs in young and middle-aged women. However, in light of the heterogeneity of clinical study designs and the lack of consensus regarding the dosage regimen and formulation to use, cranberry products cannot be recommended for the prophylaxis of recurrent UTIs at this time.

Cranberry derived proanthocyanidins reduce bacterial adhesion to selected biomaterials.

Posted: November 4, 2010
Authors: Eydelnant IA, Tufenkji N

Abstract: Catheter associated urinary tract infections (CAUTI) linked with the uropathogens Escherichia coli (E. coli) and Enterococcus faecalis (E. faecalis) account for the majority of nosocomial infections acquired in the clinical environment. Because these infections develop following initial adhesion of the bacterial pathogens to the catheter surface, there is increased interest in developing effective methods to inhibit attachment of cells to biomaterials used in the manufacture of indwelling devices. High molecular weight proanthocyanidins (PAC) extracted from the North American cranberry (Vaccinium macrocarpon) were examined for their potential to reduce the initial adhesion of uropathogenic bacteria (E. coli CFT073 and E. faecalis 29212) to two model biomaterials, poly(vinyl chloride) (PVC) and polytetrafluoroethylene (PTFE). Well-controlled experiments conducted in a parallel-plate flow chamber (PPFC) demonstrated decreased attachment of both bacteria to PVC and PTFE when either the bacteria, biomaterial or both surfaces were treated with PAC. Most significant inhibition of bacterial adhesion was observed for the condition where both the bacteria and biomaterial surfaces were coated with PAC. Additional experiments conducted with nonbiological model particles demonstrate comparable extents of adhesion inhibition, supporting a nonbiospecific mechanism of PAC action. The results of this study are promising for the implementation of PAC in the clinical milieu for prevention of device associated infection as the proposed functional modification is independent of antibacterial mechanisms that may give rise to resistant strains.

Cranberry juice improved antioxidant status without affecting bone quality in orchidectomized male rats.

Posted: November 4, 2010
Authors: Villarreal A, Stoecker BJ, Garcia C, Garcia K, Rios R, Gonzales C, Mandadi K, Faraji B, Patil BS, Deyhim F.
Journal: Phytomedicine 14(12):815-20

Abstract: BACKGROUND: We reported that drinking citrus juice improves bone quality in orchidectomized senescent male rats. Because cranberry juice, like citrus, is rich in nutrients and phenolic compounds, beneficial effects of citrus juice might also be seen with cranberry juice. An experiment evaluated effect of drinking cranberry juice on bone quality in orchidectomized rats.

METHODS: Thirty-two 1-year-old male rats were randomized to two groups: a sham-control group (n=8) and an orchidectomized group (n=24). The treatments for the 4 months duration of the study were SHAM, orchidectomy (ORX), ORX+drinking either 27% or 45% cranberry juice concentrate added to drinking water. At the termination of the study, the rats were euthanized, blood was collected for plasma antioxidant status and IGF-I. The femur, tibia and the 4th lumbar were evaluated for bone quality. Total calcium and magnesium concentration in the femurs were also evaluated.

RESULTS: ORX did not affect red blood cell (RBC)-induced hemolysis despite lowering (p<0.05) plasma antioxidant capacity; reduced (p<0.05) plasma IGF-I, femoral density, femoral strength, time-induced femoral fracture, bone mineral content, bone mineral area; numerically (p=0.07) lowered 4th lumbar density; decreased (p<0.05) trabecular connectivity, trabecular number, femoral ash; increased (p<0.05) trabecular separation in comparison to the SHAM group. Drinking cranberry juice increased (p<0.05) plasma antioxidant status, protected RBC against hemolysis, but had no positive effect on bone quality or bone mineral status.

CONCLUSIONS: Cranberry juice increases plasma antioxidant status without affecting bone quality.

Cranberry juice increases antioxidant status without affecting cholesterol homeostasis in orchidectomized rats.

Posted: November 4, 2010
Authors: Deyhim F, Patil BS, Villarreal A, Lopez E, Garcia K, Rios R, Garcia C, Gonzales C, Mandadi K.
Journal: J Med Food 10(1):49-53

Abstract: Oxidative stress and hypogonadism are linked to the increased incidence of cardiovascular disease in males. The objective of this research was to delineate whether drinking cranberry juice for 4 months affects antioxidant capacity and lipid profile in orchidectomized rats. Thirty-two 1-year-old male rats were randomized to two groups: a sham-control group (n = 8) and an orchidectomized group (n = 24). The orchidectomized group was divided into three groups of eight and assigned to one of the following treatments: orchidectomy, orchidectomy plus 27% cranberry juice, and orchidectomy plus 45% cranberry juice. At 120 days after initiation of the study, all rats were killed, blood was collected, and plasma was harvested for total antioxidant status, malondialdehyde, nitrate + nitrite, and superoxide dismutase (SOD) activity in liver, and concentrations of cholesterol and triglyceride in liver and in plasma. Orchidectomy depressed (P < .05) plasma antioxidant capacity and SOD activity, elevated (P < .05) nitrate + nitrite and malondialdehyde in plasma, and increased (P < .05) triglyceride and cholesterol values in liver and in plasma. Cranberry juice increased (P < .05) plasma antioxidant capacity and SOD activity and reduced (P < .05) nitrate + nitrite and malondialdehyde concentrations. Drinking cranberry juice did not affect cholesterol concentrations in liver and in plasma. Triglyceride concentration in plasma of orchidectomized rats that were drinking cranberry juice increased (P < .05), but its concentration in liver decreased (P < .05) to the level of shams. The protective effect of cranberry juice from oxidative damage may be mediated by a decrease in nitrate + nitrite and dose-dependent decrease in peroxidation.

Cranberry phytochemical extract inhibits SGC-7901 cell growth and human tumor xenografts in Balb/c nu/nu mice

Posted: November 4, 2010
Authors: Liu M, Lin LQ, Song BB, Wang LF, Zhang CP, Zhao JL, Liu JR
Journal: J Agric Food Chem 57(2):762-8

Abstract: Cranberry extract possesses potent antioxidant capacity and antiproliferative activity against cancer in vitro and in vivo. The objectives of this study were to determine whether the cranberry extract inhibited proliferation of human gastric cancer SGC-7901 cells and human gastric tumor xenografts in the Balb/c nu/nu mouse. Cranberry extract at doses of 0, 5, 10, 20, and 40 mg/mL significantly inhibited proliferation of SGC-7901 cells, and this suppression was partly attributed to decreased PCNA expression and apoptosis induction. In a human tumor xenograft model, the time of human gastric tumor xenografts in the mouse was delayed in a dose-dependent manner. A dose-response inhibition was also observed in the averages of size, weight, and volume of tumor xenografts in the mouse between the control and cranberry-treated groups. These results demonstrate fresh cranberries to be a chemopreventive reagent.

Cranberry phytochemical extracts induce cell cycle arrest and apoptosis in human MCF-7 breast cancer cells.

Posted: November 4, 2010
Authors: Sun J, Hai Liu R.
Journal: Cancer Lett 241(1):124-34

Abstract: Breast cancer is the most commonly diagnosed cancer in women in the US and is one of the leading causes of death due to cancer. Epidemiological studies have consistently suggested the inverse association between cancer risk and intake of fruits and vegetables. These health benefits have been linked to the additive and synergistic combination of phytochemicals in fruits and vegetables. Cranberries have been shown to possess anti-carcinogenic activities such as inhibition of growth of several cancer cell lines, and inhibition of ornithine decarboxylase (ODC) activity in vitro. However, the molecular mechanisms of the anti-cancer properties of cranberry phytochemical extracts have not been completely understood. Our data showed that cranberry phytochemical extracts significantly inhibited human breast cancer MCF-7 cell proliferation at doses of 5 to 30mg/mL (P<0.05). Apoptotic induction in MCF-7 cells was observed in a dose-dependent manner after exposure to cranberry phytochemical extracts for 4h. Cranberry phytochemical extracts at a dose of 50mg/mL resulted in a 25% higher ratio of apoptotic cells to total cells as compared to the control groups (P<0.05). Cranberry phytochemical extracts at doses from 10 to 50mg/mL significantly arrested MCF-7 cells at G0/G1 phase (P<0.05). A constant increasing pattern of the G1/S index was observed in the cranberry extract treatment group while the G1/S ratio of the control group decreased concomitantly between 10 and 24h treatment. After 24-h exposure to cranberry extracts, the G1/S index of MCF-7 cells was approximately 6 times higher than that of the control group (P<0.05). These results suggest that cranberry phytochemical extracts possess the ability to suppress the proliferation of human breast cancer MCF-7 cells and this suppression is at least partly attributed to both the initiation of apoptosis and the G1 phase arrest.

Cranberry proanthocyanidins inhibit MMP production and activity

Posted: November 4, 2010
Authors: La VD, Howell AB, Grenier D
Journal: J Dent Res 88(7):627-32

Abstract: Matrix metalloproteinases (MMPs) produced by resident and inflammatory cells in response to periodontopathogens play a major role in periodontal tissue destruction. Our aim was to investigate the effects of A-type cranberry proanthocyanidins (AC-PACs) on: (i) the production of various MMPs by human monocyte-derived macrophages stimulated with Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS), and (ii) the catalytic activity of recombinant MMP-1 and MMP-9. The effects of AC-PACs on the expression of 5 protein kinases and the activity of nuclear factor-kappa B (NF-kappaB) p65 in macrophages stimulated with LPS were also monitored. Our results indicated that AC-PACs inhibited the production of MMPs in a concentration-dependent manner. Furthermore, the catalytic activity of MMP-1 and MMP-9 was also inhibited. The inhibition of MMP production was associated with reduced phosphorylation of key intracellular kinases and the inhibition of NF-kappaB p65 activity. AC-PACs thus show potential for the development of novel host-modulating strategies to inhibit MMP-mediated tissue destruction during periodontitis.

Cytoprotective effect of proanthocyanidin-rich cranberry fraction against bacterial cell wall-mediated toxicity in macrophages and epithelial cells.

Posted: November 4, 2010
Authors: La VD, Labrecque J, Grenier D
Journal: Phytother Res 23(10):1449-52

Abstract: Recent studies brought evidence regarding the potential beneficial effects of cranberry polyphenols for periodontal infections. In this study, we evaluated the capacity of a proanthocyanidin-rich cranberry fraction to protect macrophages and oral epithelial cells against cytotoxicity induced by bacterial components. U937 cells, differentiated into adherent macrophage-like cells, as well as oral epithelial cells were treated with cell wall or lipopolysaccharide preparations from periodontopathogens. Cell viability was monitored using a commercial MTT (3-[4,5-diethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. The cytoprotective effect was evaluated by pre-incubating human cells with a proanthocyanidin-rich cranberry fraction prior to treatment with the bacterial components at toxic concentrations. Among the various bacterial components tested, Peptostreptotoccus micros cell wall was found to be the most toxic for macrophages and epithelial cells and was thus selected for further analyses. Treatment of monocyte-derived macrophages with cell wall of P. micros (20 microg/ml) decreased the cell viability by approximately 50%. Adding the cranberry fraction prior to treating cells with P. micros cell wall dose-dependently protected monocyte-derived macrophages from the toxic effect. A dose-dependent cytoprotective effect of the cranberry fraction was also observed with oral epithelial cells treated with P. micros cell wall. This study suggests that cranberry polyphenols may exert a protective effect for host cells against the toxicity induced by bacterial components

Effect of cranberry extracts on lipid profiles in subjects with Type 2 diabetes

Posted: November 4, 2010
Authors: Lee IT, Chan YC, Lin CW, Lee WJ, Sheu WH
Journal: Diabet Med 25(12):1473-7

Abstract: AIM: To examine the effect of cranberry ingestion on lipid profiles in Type 2 diabetic patients taking oral glucose-lowering drugs.

METHODS: Thirty Type 2 diabetic subjects (16 males and 14 females; mean age 65 +/- 1 years) who were taking oral glucose-lowering medication regularly were enrolled in this randomized, placebo-controlled, double-blind study. Changes in lipid profiles, oxidized low-density lipoprotein (ox-LDL), glycaemic control, components of the metabolic syndrome, C-reactive protein (CRP) and urinary albumin excretion (UAE) were assessed after cranberry or placebo treatment for 12 weeks.

RESULTS: Low-density lipoprotein (LDL) cholesterol decreased significantly in the cranberry group (from 3.3 +/- 0.2 to 2.9 +/- 0.2 mmol/l, P = 0.005) and the decrease was significantly greater than that in the placebo group (-0.4 +/- 0.1 vs. 0.2 +/- 0.1 mmol/l, P < 0.001). Total cholesterol and total : high-density lipoprotein (HDL) cholesterol ratio also decreased significantly (P = 0.020 and 0.044, respectively) in the cranberry group and the reductions were significantly different from those in the placebo group (P < 0.001 and P = 0.032, respectively). However, ox-LDL levels did not change significantly in response to cranberry consumption. Neither fasting glucose nor glycated haemoglobin improved in either group. Changes in components of the metabolic syndrome, UAE and CRP were not significantly different between groups.

CONCLUSIONS: Cranberry supplements are effective in reducing atherosclerotic cholesterol profiles, including LDL cholesterol and total cholesterol levels, as well as total : HDL cholesterol ratio, and have a neutral effect on glycaemic control in Type 2 diabetic subjects taking oral glucose-lowering agents.

Effectiveness of a cranberry (Vaccinium macrocarpon) preparation in reducing asymptomatic bacteriuria in patients with an ileal enterocystoplasty.

Posted: November 4, 2010
Authors: Botto H, Neuzillet Y
Journal: Scand J Urol Nephrol 44(3):165-8

Abstract: OBJECTIVE: Bacteriuria is a usual complication of enterocystoplasty following cystectomy. Cranberry products may decrease the number of urinary tract infections because of a non-dialysable compound, a condensed tannin, the proanthocyanidin (PAC) type A. This study determined the effectiveness of treatment with a cranberry preparation highly dosed in proanthocyanidin A in prevention of repeated bacteriuria in patients with an ileal enterocystoplasty.

MATERIAL AND METHODS: Between November 2004 and November 2009, a controlled study was open to patients seen in consultation for follow-up after a radical cystectomy and ileal cystoplasty. Patients had a history of repeated urinary infection and/or bacteriuria during the pretreatment phase. During the treatment phase, patients received a cranberry (Vaccinium macrocarpon) preparation highly dosed in proanthocyanidin A (36 mg measured by the dimethylaminocinnamaldehyde method), one capsule a day. The primary endpoint was the absence of bacteria in urine culture. The secondary endpoints were the presence or absence of symptoms (pain, fever), continence status and upper excretory tract enlargement. Each patient was his or her own historical control.

RESULTS: Fifteen patients were included. The median duration of the period without treatment with cranberry compound was 18.5 (1-93) months. The median duration of the period with treatment with cranberry compound was 32.8 (13-60) months. There was a significant decrease in the number of positive urine cultures during cranberry compound treatment.

CONCLUSIONS: Treatment with a cranberry compound seems to be effective in reducing asymptomatic bacteriuria in patients with an ileal enterocystoplasty. These results need to be validated by further double-blind randomized studies.

Effects of a flavonol-rich diet on select cardiovascular parameters in a Golden Syrian hamster model.

Posted: November 4, 2010
Authors: Kalgaonkar S, Gross HB, Yokoyama W, Keen CL
Journal: J Med Food 13(1):108-15

Abstract: The concept that the consumption of a diet rich in flavonoids can be associated with a reduced risk for cardiovascular disease is becoming increasingly accepted. In the present study we investigated the effects of the following four diets on blood pressure and cholesterol ester levels in hypercholesterolemic Golden Syrian hamsters: a high-fat, high-cholesterol diet (HFHC); a HFHC with 2% cranberry concentrate powder (HFHC+CE); a HFHC with 0.1% rutin (HFHC+Rutin); and a HFHC with 30 mg/kg vitamin E (HFHC+Vit.E). Diets were fed for either 12 or 20 weeks. Over the experimental period, heart rate and blood pressure measurements increased in the animals fed HFHC and HFHC+Vit.E; in contrast, these measurements were not increased in the animals fed HFHC+CE and HFHC+Rutin. Mesenteric and total abdominal fat were significantly lower in the animals fed HFHC+Rutin than in animals fed the other three diets. Ratios of plasma high-density lipoprotein cholesterol (HDL-C) to very-low-density lipoprotein cholesterol and of plasma HDL-C to low-density lipoprotein cholesterol were significantly higher in animals consuming HFHC+Vit.E than in animals fed the other three diets. Aortic cholesteryl ester levels were significantly lower in animals fed HFHC+CE, HFHC+Rutin, and HFHC+Vit.E at 20 weeks than in the animals fed HFHC. Fasting blood glucose concentrations were significantly lower in animals fed HFHC+Rutin and HFHC+Vit.E, and glucose clearance rates improved in animals fed HFHC+Rutin compared to animals fed the other three diets. Results obtained from this study support the concept that the chronic consumption of a flavonoid-rich diet can be beneficial

Evaluation of cranberry tablets for the prevention of urinary tract infections in spinal cord injured patients with neurogenic bladder.

Posted: November 4, 2010
Authors: Hess MJ, Hess PE, Sullivan MR, Nee M, Yalla SV
Journal: Spinal Cord 46(9):622-6

Abstract: STUDY DESIGN: Randomized, double blind, placebo-controlled trial with a crossover design.

OBJECTIVE: To evaluate cranberry tablets for the prevention of urinary tract infection (UTI) in spinal cord injured (SCI) patients.

SETTING: Spinal Cord Injury Unit of a Veterans Administration Hospital, MA, USA.

METHODS: Subjects with spinal cord injury and documentation of neurogenic bladder were randomized to receive 6 months of cranberry extract tablet or placebo, followed by the alternate preparation for an additional 6 months. The primary outcome was the incidence of UTI.

RESULTS: Forty-seven subjects completed the trial. We found a reduction in the likelihood of UTI and symptoms for any month while receiving the cranberry tablet (P<0.05 for all). During the cranberry period, 6 subjects had 7 UTI, compared with 16 subjects and 21 UTI in the placebo period (P<0.05 for both number of subjects and incidence). The frequency of UTI was reduced to 0.3 UTI per year vs 1.0 UTI per year while receiving placebo. Subjects with a glomerular filtration rate (GFR) greater than 75 ml min(-1) received the most benefit.

CONCLUSION: Cranberry extract tablets should be considered for the prevention of UTI in SCI patients with neurogenic bladder. Patients with a high GFR may receive the most benefit.

Influence of cranberry juice on glucan-mediated processes involved in Streptococcus mutans biofilm development.

Posted: November 4, 2010
Authors: Koo H, Nino de Guzman P, Schobel BD, Vacca Smith AV, Bowen WH.
Journal: Caries Res 40(1):20-27

Abstract: Cranberry juice (CJ) has biological properties that may provide health benefits. In this study, we investigated the influence of CJ (pH 5.5) on several activities in vitro associated with the development of Streptococcus mutans UA159 biofilms. The ability of CJ to influence the adherence of S. mutans to either saliva- (sHA) or glucan-coated hydroxyapatite (gsHA), and to inhibit the glucan production by purified glucosyltransferases adsorbed to sHA was determined. For the adherence assays, we used both uncoated and saliva-coated bacterial cells. Furthermore, we examined whether CJ interferes with the viability, development, polysaccharide composition and acidogenicity of S. mutans biofilms. A solution containing equivalent amounts of glucose, fructose and organic acids at pH 5.5 was used as negative control. The adherence of S. mutans (uncoated and saliva-coated) to either sHA or gsHA treated with 25% CJ (v/v) was remarkably reduced (40-85% inhibition compared to control: p < 0.05), indicating that CJ effectively blocked the bacterial adherence to binding sites in salivary pellicle and in glucans. In contrast, when the bacterial cells alone were treated with CJ they adhered to the similar untreated surfaces. Cranberry juice (25%, v/v) also inhibited the activities of surface-adsorbed GTF B and C (70-80% inhibition compared to control, p < 0.05). The effect of CJ on the viability of microorganisms in biofilms was not significant. Biofilm formation and accumulation were significantly reduced by topical applications of 25% CJ (v/v) twice daily with 1-min exposures (p < 0.05). The biomass and insoluble glucan content of the biofilms in addition to its acidogenicity were significantly reduced by cranberry treatments (p < 0.05). Our data show that cranberry juice inhibited glucan-mediated biofilm development and acid production, and holds promise as a natural product to prevent biofilm-related oral diseases.

Influence of cranberry proanthocyanidins on formation of biofilms by Streptococcus mutans on saliva-coated apatitic surface and on dental caries development in vivo.

Posted: November 4, 2010
Authors: Koo H, Duarte S, Murata RM, Scott-Anne K, Gregoire S, Watson GE, Singh AP, Vorsa N.
Journal: Caries Res 44(2):116-126

Abstract: Cranberry crude extracts, in various vehicles, have shown inhibitory effects on the formation of oral biofilms in vitro. The presence of proanthocyanidins (PAC) in cranberry extracts has been linked to biological activities against specific virulence attributes of Streptococcus mutans, e.g. the inhibition of glucosyltransferase (Gtf) activity. The aim of the present study was to determine the influence of a highly purified and chemically defined cranberry PAC fraction on S. mutans biofilm formation on saliva-coated hydroxyapatite surface, and on dental caries development in Sprague-Dawley rats. In addition, we examined the ability of specific PAC (ranging from low-molecular-weight monomers and dimers to high-molecular-weight oligomers/polymers) to inhibit GtfB activity and glycolytic pH drop by S. mutans cells, in an attempt to identify specific bioactive compounds. Topical applications (60-second exposure, twice daily) with PAC (1.5 mg/ml) during biofilm formation resulted in less biomass and fewer insoluble polysaccharides than the biofilms treated with vehicle control had (10% ethanol, v/v; p < 0.05). The incidence of smooth-surface caries in rats was significantly reduced by PAC treatment (twice daily), and resulted in less severe carious lesions compared to the vehicle control group (p < 0.05); the animals treated with PAC also showed significantly less caries severity on sulcal surfaces (p < 0.05). Furthermore, specific A-type PAC oligomers (dimers to dodecamers; 0.1 mg/ml) effectively diminished the synthesis of insoluble glucans by GtfB adsorbed on a saliva-coated hydroxyapatite surface, and also affected bacterial glycolysis. Our data show that cranberry PAC reduced the formation of biofilms by S. mutans in vitro and dental caries development in vivo, which may be attributed to the presence of specific bioactive A-type dimers and oligomers.

Inhibitory effect of cranberry polyphenol on biofilm formation and cysteine proteases of Porphyromonas gingivalis

Posted: November 4, 2010
Authors: Yamanaka A, Kouchi T, Kasai K, Kato T, Ishihara K, Okuda K.
Journal: J Periodontal Res 42(6):589-592

Abstract: BACKGROUND AND OBJECTIVE: The purpose of this study was to investigate the effects of cranberry polyphenol fraction on biofilm formation and activities of Arg-gingipain and Lys-gingipain in Porphyromonas gingivalis. MATERIAL AND METHODS: The polyphenol fraction was prepared by using a glass column packed with Amberlite XAD 7HP and 70% aqueous ethanol as an elution solvent. RESULTS: Synergistic biofilm formation by P. gingivalis and Fusobacterium nucleatum was significantly inhibited by the polyphenol fraction at a concentration of 250 microg/mL compared with untreated controls (p < 0.01). Arg-gingipain and Lys-gingipain activities in P. gingivalis ATCC 33277 and FDC 381 were inhibited significantly at a polyphenol fraction concentration of > or = 1 microg/mL (p < 0.05). CONCLUSION: These findings indicate that the polyphenol fraction inhibits biofilm formation and the Arg-gingipain and Lys-gingipain activities of P. gingivalis.

Inhibitory effects of cranberry juice on attachment of oral streptococci and biofilm formation

Posted: November 4, 2010
Authors: Yamanaka A, Kimizuka R, Kato T, Okuda K
Journal: Oral Microbiol Immunol 19(3):150-4

Abstract: Cranberry juice is known to inhibit bacterial adhesion. We examined the inhibitory effect of cranberry juice on the adhesion of oral streptococci strains labeled with [3H]-thymidine to saliva-coated hydroxyapatite beads (s-HA). When the bacterial cells were momentarily exposed to cranberry juice, their adherence to s-HA decreased significantly compared with the control (P < 0.01). Their hydrophobicity also decreased dependently with the concentration of cranberry juice. We also evaluated the inhibitory effect of cranberry juice on biofilm formation. By using a microplate system, we found that the high molecular mass constituents of cranberry juice inhibited the biofilm formation of the tested streptococci. The inhibitory activity was related to the reduction of the hydrophobicity. The present findings suggest that cranberry juice component(s) can inhibit colonization by oral streptococci to the tooth surface and can thus slow development of dental plaque.

Long-term effects of three commercial cranberry products on the antioxidative status in rats: a pilot study.

Posted: November 4, 2010
Authors: Palikova I, Vostalova J, Zdarilova A, Svobodova A, Kosina P, Vecera R, Stejskal D, Proskova J, Hrbac J, Bednar P, Maier V, Cernochova D, Simanek V, Ulrichova J.
Journal: J Agric Food Chem 8(3):1672-8

Abstract: Cranberry (Vaccinium macrocarpon Ait. Ericaceae) fruits and juice are widely used for their antiadherence and antioxidative properties. Little is known however about their effects on clinical chemistry markers after long-term consumption. This study was conducted to evaluate the effect of three commercial cranberry products, NUTRICRAN90S, HI-PAC 4.0, and PACRAN on the antioxidative status of rodents, divided into three experimental groups. The products were given as dietary admixtures (1500 mg of product/kg of stock feed) for 14 weeks to male Wistar rats (Groups 2-4) and a control Group 1 which received only stock feed. There were no significant cranberry treatment-related effects on oxidative stress parameters, catalase, glutathione peroxidase, glutathione reductase, glutathione transferase, superoxide dismutase, total antioxidant capacity, thiobarbituric acid reactive substances, advanced oxidation protein products, total SH-groups, or any other measured clinical chemistry markers. Hematological parameters, body weight, and food consumption were also unaffected by intake of cranberries. Only liver glutathione reductase activity and glutathione levels were significantly lower in Group 4 than in Group 1. Plasma alkaline phosphatase alone was significantly decreased in Group 2. No gross pathology, effects on organ weights, or histopathology were observed. No genotoxicity was found, and total cytochrome P450 level in liver was unaffected in all groups. The levels of hippuric acid and several phenolic acids were significantly increased in plasma and urine in Groups 2-4. The concentration of anthocyanins was under the detection threshold. The dietary addition of cranberry powders for 14 weeks was well tolerated, but it did not improve the antioxidative status in rats.

Recurrent urinary tract infections in older people: the role of cranberry products

Posted: November 4, 2010
Authors: Sumukadas D, Davey P and McMurdo ME
Journal: Age Ageing 38(3):255-7

Abstract: No abstract - Introduction: Urinary tract infections (UTI) are the commonest bacterial infection in older people. Half of all women experience at least one UTI and the risk increases with age. The present management of recurrent urinary tract infection is prophylaxis with low-dose, long-term antibiotics. However, there is a growing reluctance to prescribe antibiotics unless absolutely essential because of fears about antimicrobial resistance. So the recent resurgence in interest in the potential role of cranberry
products is timely.

The antifungal activity of urine after ingestion of cranberry products.

Posted: November 4, 2010
Authors: Lee YL, Owens J, Thrupp L, Barron S, Shanbrom E, Cesario T, Najm WI
Journal: J Altern Complement Med 15(9):957-8

Abstract: No abstract - Introduction: Cranberry (Vacinicum macrocarpon) is traditionally used in folk medicine for treatment of urinary tract infections. In a recent study, we established that in addition to the antiadhesion effects, concentrated cranberry juice had a direct antimicrobial effect in vitro. We were also able to confirm a direct antimicrobial activity in vitro against a strain of Klebsiella
pneumoniae, in the urine of subjects after ingestion of a commercial cranberry product. While bacteria are the most common cause of urinary tract infections, frequent or prolonged antimicrobial therapy, use of catheters, severely ill patients, high plasma glucose, and invasive procedures can often lead to candiduria. A review of the literature identified one study (Swartz and Medrek 1968), which reported that cranberry juice (40%) in Sabouraud’s dextrose agar had minimal effect on the growth of Candida albicans compared to 0.087% benzoic acid. In this study, we evaluate the anti-Candida activity of urine specimens after ingestion of cranberry.

A-Type proanthocyanidin trimers from cranberry that inhibit adherence of uropathogenic P-fimbriated Escherichia coli.

Posted: November 2, 2010
Authors: Foo LY, Lu Y, Howell AB, Vorsa N.
Journal: J Nat Prod 63:1225-1228

Abstract: Three proanthocyanidin trimers possessing A-type interflavanoid linkages, epicatechin-(4beta-->6)-epicatechin-(4beta-->8, 2beta-->O-->7)-epicatechin (4), epicatechin-(4beta-->8, 2beta-->O-->7)-epicatechin-(4beta-->8)-epicatechin (5), and epicatechin-(4beta-->8)-epicatechin-(4beta-->8, 2beta-->O-->7)-epicatechin (6), were isolated from the ripe fruits of Vaccinium macrocarpon (cranberry) and prevented adherence of P-fimbriated Escherichia coli isolates from the urinary tract to cellular surfaces containing alpha-Gal(1-->4)beta-Gal receptor sequences similar to those on uroepithelial cells. The structure of 4 was elucidated by a combination of spectroscopic methods and acid-catalyzed degradation with phloroglucinol. Also isolated were the weakly active epicatechin-(4beta-->8, 2beta-->O-->7)-epicatechin (procyanidin A2) (3) and the inactive monomer epicatechin (1) and the inactive dimer epicatechin-(4beta-->8)-epicatechin (procyanidin B2) (2).

Can a concentrated cranberry extract prevent recurrent urinary tract infections in women? A pilot study.

Posted: November 2, 2010
Authors: Bailey DT, Dalton C, Joseph Daugherty F, Tempesta MS
Journal: Phytomedicine 14(4):237-41

Abstract: BACKGROUND: Urinary tract infections (UTIs) are extremely prevalent and despite treatment with antibiotics, reoccurrences are common causing frustration in the patient and the potential for developing antibiotic resistance. The use of cranberry products to prevent UTIs has recently become popular and more clinical studies are needed to explore this use.

OBJECTIVE: This open label pilot study examined the ability of a concentrated cranberry preparation to prevent UTIs in women with a history of recurrent infections.

SUBJECTS: Women between the ages of 25 and 70 years old were included with a history of a minimum of 6 UTIs in the proceeding year.

INTERVENTION: The women took one capsule twice daily for 12 weeks containing 200 mg of a concentrated cranberry extract standardized to 30% phenolics.

DESIGN: A questionnaire was used initially to determine the patient's medical history and they were asked at monthly intervals if any of the information had changed. All of the women in the study had urinalysis within 24h before starting on the study preparation and once a month after that for 4 months. Subjects were followed-up approximately 2 years later.

RESULTS: All 12 subjects participated in the 12-week study and were available for follow up 2 years later. During the study none of the women had a UTI. No adverse events were reported. Two years later, eight of the women who continue to take cranberry, continue to be free from UTIs.

CONCLUSION: A cranberry preparation with a high phenolic content may completely prevent UTIs in women who are subject to recurrent infections.

PMID: 17296290 [PubMed - indexed for MEDLINE]

Can cranberry juice be a substitute for cefaclor prophylaxis in children with vesicoureteral reflux?

Posted: November 2, 2010
Authors: Nishizaki N, Someya T, Hirano D, Fujinaga S, Ohtomo Y, Shimizu T and Kaneko K
Journal: Pediatr Int 51(3):433-4

Abstract: No abstract - Introduction: Urinary tract infection (UTI) is a common childhood infection. In 30–50% of children with UTI the infections occur recurrently, especially in those with vesicoureteral reflux (VUR), resulting in hospitalizations, and long-term health problems, such as renal scars, hypertension, and end-stage renal disease. To reduce the likelihood of recurrent UTI for children with VUR, antibiotics prophylaxis has been regarded as the therapeutic standard for many years. However, the disadvantage of long-term antibiotic therapy is the potential for development of resistant organisms in the host.

Although cranberry juice prophylaxis was found to reduce the frequency of bacteriuria with pyuria in older women, no studies have yet been reported in the literature on children with VUR. The purpose of this study was to examine whether cranberry juice can be substituted for antibiotic prophylaxis in the prevention of UTI in children with VUR.

Cranberries inhibit LDL oxidation and induce LDL receptor expression in hepatocytes

Posted: November 2, 2010
Authors: Chu YF, Liu RH
Journal: Life Sci 77(15):1892-901

Abstract: Cardiovascular disease (CVD) is the leading cause of death in most industrialized countries. Cranberries were evaluated for their potential roles in dietary prevention of CVD. Cranberry extracts were found to have potent antioxidant capacity preventing in vitro LDL oxidation with increasing delay and suppression of LDL oxidation in a dose-dependent manner. The antioxidant activity of 100 g cranberries against LDL oxidation was equivalent to 1000 mg vitamin C or 3700 mg vitamin E. Cranberry extracts also significantly induced expression of hepatic LDL receptors and increased intracellular uptake of cholesterol in HepG2 cells in vitro in a dose-dependent manner. This suggests that cranberries could enhance clearance of excessive plasma cholesterol in circulation. We propose that additive or synergistic effects of phytochemicals in cranberries are responsible for the inhibition of LDL oxidation, the induced expression of LDL receptors, and the increased uptake of cholesterol in hepatocytes.

Cranberry juice suppressed the diclofenac metabolism by human liver microsomes, but not in healthy human subjects

Posted: November 2, 2010
Authors: Ushijima K, Tsuruoka S, Tsuda H, Hasegawa G, Obi Y, Kaneda T, Takahashi M
Journal: Br J Clin Pharmacol 68(2):194-200

Abstract: AIM: To investigate a potential interaction between cranberry juice and diclofenac, a substrate of CYP2C9.

METHODS: The inhibitory effect of cranberry juice on diclofenac metabolism was determined using human liver microsome assay. Subsequently, we performed a clinical trial in healthy human subjects to determine whether the repeated consumption of cranberry juice changed the diclofenac pharmacokinetics.

RESULTS: Cranberry juice significantly suppressed diclofenac metabolism by human liver microsomes. On the other hand, repeated consumption of cranberry juice did not influence the diclofenac pharmacokinetics in human subjects.

CONCLUSIONS: Cranberry juice inhibited diclofenac metabolism by human liver microsomes, but not in human subjects. Based on the present and previous findings, we think that although cranberry juice inhibits CYP2C9 activity in vitro, it does not change the pharmacokinetics of medications metabolized by CYP2C9 in clinical situations.

Cranberry proanthocyanidins are cytotoxic to human cancer cells and sensitize platinum-resistant ovarian cancer cells to paraplatin

Posted: November 2, 2010
Authors: Singh AP, Singh RK, Kim KK, Satyan KS, Nussbaum R, Torres M, Brard L and Vorsa N
Journal: Phytother Res 23(8):1066-74

Abstract: Polyphenolic extracts of the principal flavonoid classes present in cranberry were screened in vitro for cytotoxicity against solid tumor cells lines, identifying two fractions composed principally of proanthocyanidins (PACs) with potential anticancer activity. Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF-MS) analysis of the proanthocyanidins (PACs) fractions indicated the presence of A-type PACs with 1-4 linkages containing between 2-8 epicatechin units with a maximum of 1 epigallocatechin unit. PACs exhibited in vitro cytotoxicity against platinum-resistant human ovarian, neuroblastoma and prostate cancer cell lines (IC50 = 79-479 microg/mL) but were non-cytotoxic to lung fibroblast cells (IC50 > 1000 microg/ml). SKOV-3 ovarian cancer cells treated with PACs exhibited classic apoptotic changes. PACs acted synergistically with paraplatin in SKOV-3 cells. Pretreatment of SKOV-3 cells with PACs (106 microg/ml) resulted in a significant reduction of the paraplatin IC50 value. Similarly, in a BrdU incorporation assay, co-treatment of SKOV-3 cells with PACs and paraplatin revealed reduced cell proliferation at lower concentrations than with either individually. In SKOV-3 cell cultures co-treated with PAC-1 and paraplatin, an HPLC analysis indicated differential quantitative presence of various PAC oligomers such as DP-8, -9, -11 and -14 indicating either selective binding or uptake. Cranberry proanthocyanidins exhibit cell-line specific cytotoxicity, induce apoptotic markers and augment cytotoxicity of paraplatin in platinum-resistant SKOV-3 ovarian cancer cells.

Growth inhibitory action of cranberry on Helicobacter pylori.

Posted: November 2, 2010
Authors: Matsushima M, Suzuki T, Masui A, Kasai K, Kouchi T, Takagi A, Shirai T, Mine T
Journal: J Gastroenterol Hepatol 23(Suppl 2):S175-80

Abstract: BACKGROUND AND AIM: Cranberry is a fruit that originated in North America, and it has been used by Native Americans for bacterial infections. Recent studies have revealed it to be effective for preventing refractory urinary infections, while also suggesting that it plays a possible role in the eradication of Helicobacter pylori (H. pylori).

METHODS: The H. pylori strains used in the present study were NCTC11637 and 11638. Sugar and organic acid-rich, and polyphenol-rich fractions were obtained from cranberry juice concentrate by Amberlite XAD7HP-column chromatography. The H. pylori growth inhibition was estimated by OD(660) and titration in liquid culture, and by an agar dilution plate method. The shapes of the bacteria were analyzed by scanning electron microscopy.

RESULTS: Cranberry extract suppressed bacterial proliferation in a dose-dependent manner. In the comparison with other juices, polyphenol-rich fruits (cranberries, blueberries, and red grapes) showed similar growth inhibitory activity, whereas polyphenol-poor fruits (oranges, pineapples, apples, and white grapes) did not show any activity. The polyphenol-rich fraction of cranberry maintained the H. pylori-growth inhibitory activity. More bacteria in a coccoid form were observed after culture with cranberry.

CONCLUSION: Cranberry extract inhibited H. pylori proliferation and it is suggested that polyphenols are responsible for this action. The morphological analysis suggested that cranberry induces H. pylori to develop a coccoid form, thereby inhibiting its growth bacteriostatically. Further basic studies to clarify these mechanisms in combination with in vivo studies are needed.

Identification of a cranberry juice product that inhibits enteric CYP3A-mediated first-pass metabolism in humans

Posted: November 2, 2010
Authors: Ngo N, Yan Z, Graf TN, Carrizosa DR, Kashuba AD, Dees EC, Oberlies NH, Paine MF.
Journal: Drug Metabol Dispos 37(3):514-22

Abstract: An in vivo study in rats showed a cranberry juice product to inhibit the intestinal first-pass metabolism of the CYP3A substrate nifedipine. However, a clinical study involving the CYP3A probe substrate midazolam and a different cranberry juice product showed no interaction. Because the composition of bioactive components in natural products can vary substantially, a systematic in vitro-in vivo approach was taken to identify a cranberry juice capable of inhibiting enteric CYP3A in humans. First, the effects of five cranberry juices, coded A through E, were evaluated on midazolam 1'-hydroxylation activity in human intestinal microsomes. Juice E was the most potent, ablating activity at 0.5% juice (v/v) relative to control. Second, juice E was fractionated to generate hexane-, chloroform-, butanol-, and aqueous-soluble fractions. The hexane- and chloroform-soluble fractions at 50 microg/ml were the most potent, inhibiting by 77 and 63%, respectively, suggesting that the CYP3A inhibitors reside largely in these more lipophilic fractions. Finally, juice E was evaluated on the oral pharmacokinetics of midazolam in 16 healthy volunteers. Relative to water, juice E significantly increased the geometric mean area under the curve (AUC)(0-infinity) of midazolam by approximately 30% (p=0.001), decreased the geometric mean 1'-hydroxymidazolam/midazolam AUC(0-infinity) ratio by approximately 40% (p<0.001), and had no effect on geometric mean terminal half-life, indicating inhibition of enteric, but not hepatic, CYP3A-mediated first-pass metabolism of midazolam. This approach both showed a potential drug interaction liability with cranberry juice and substantiated that rigorous in vitro characterization of dietary substances is required before initiation of clinical drug-diet interaction studies.

Increased salicylate concentrations in urine of human volunteers after consumption of cranberry juice.

Posted: November 2, 2010
Authors: Duthie GG, Kyle JA, Jenkinson AM, Duthie SJ, Baxter GJ, Paterson JR
Journal: J Agric Food Chem 53(8):2897-2900

Abstract: The aim of this study was to assess whether regular consumption of cranberry juice results in elevations in urinary salicylate concentrations in persons not taking salicylate drugs. Two groups of healthy female subjects (11/group) matched for age, weight, and height consumed 250 mL of either cranberry juice or a placebo solution three times a day (i.e., 750 mL/day) for 2 weeks. At weekly intervals, salicylic acid and salicyluric acid (the major urinary metabolite of salicylic acid) concentrations were determined in urine by HPLC with electrochemical detection. Concentrations of salicylic acid in plasma were also determined. Consumption of cranberry juice was associated with a marked increase (p < 0.001) of salicyluric and salicylic acids in urine within 1 week of the intervention. After 2 weeks, there was also a small but significant (p < 0.05) increase in salicylic acid in plasma. The regular consumption of cranberry juice results in the increased absorption of salicylic acid, an anti-inflammatory compound that may benefit health.

Inhibition of Helicobacter pylori in vitro by various berry extracts, with enhanced susceptibility to clarithromycin

Posted: November 2, 2010
Authors: Chatterjee A, Yasmin T, Bagchi D and Stohs SJ
Journal: Mol Cell Biochem 265(1-2):19-26

Abstract: The objective of this study was to evaluate the effects of various berry extracts, with and without clarithromycin on Helicobacter pylori. Resistance to clarithromycin by H. pylori has been reported, leading to interest in alternatives/adjuncts to therapy with clarithromycin. H. pylori American type culture collection (ATCC) strain 49503 was grown, cell suspensions were made in
PBS and diluted 10-fold. One hundred &#956;l of the suspension was then incubated for 18 h with extracts of raspberry, strawberry, cranberry, elderberry, blueberry, bilberry, and OptiBerry R , a blend of the six berries, at 0.25–1% concentrations. Serially diluted cell suspensions were exposed for 1 h to clarithromycin at 15 &#956;g/ml. Ten &#956;l of bacterial samples from the 10–7 dilution tube
were plated and incubated for 18 h and the number of colonies were counted. Growth of H. pylori was confirmed by the CLO R test. All berry extracts significantly (p < 0.05) inhibited H. pylori, compared with controls, and also increased susceptibility of H. pylori to clarithromycin, with OptiBerry R demonstrating maximal effects.

Role of cranberry on bacterial adhesion forces and implications for Escherichia coli-uroepithelial cell attachment

Posted: November 2, 2010
Authors: Pinzon-Arango PA, Liu Y and Camesano TA
Journal: J Med Food 12(2):259-270

Abstract: Previous clinical research has suggested that the consumption of cranberry products prevents the adhesion of Escherichia coli to uroepithelial cells by causing changes in bacterial fimbriae. Atomic force microscopy was used to probe the adhesion forces between E. coli (nonfimbriated strain HB101 and the P-fimbriated variant HB101pDC1) and a model surface (silicon nitride), to determine the effect of growth in cranberry products on bacterial adhesion. Bacteria were grown in tryptic soy broth supplemented with either light cranberry juice cocktail (L-CJC) or cranberry proanthocyanidins (PACs). Growth of E. coli HB101pDC1 and HB101 in L-CJC or PACs resulted in a decrease in adhesion forces with increasing number of cultures. In a macroscale bacteria-uroepithelial cell adhesion assay a decrease in bacterial attachment was observed for E. coli HB101pDC1 grown in L-CJC or PACs. This effect was reversible because bacteria that were regrown in cranberry-free medium regained their ability to attach to uroepithelial cells, and their adhesion forces reverted to the values observed in the control condition. Exposure to increasing concentrations of L-CJC resulted in a decrease of bacterial attachment to uroepithelial cells for the P-fimbriated strain after L-CJC treatment (27% by weight) and after PACs treatment (345.8 microg/mL). Cranberry products affect the surface properties, such as fimbriae and lipopolysaccharides, and adhesion of fimbriated and nonfimbriated E. coli. The concentration of cranberry products and the number of cultures the bacteria were exposed to cranberry determines how much the adhesion forces and attachment are altered.

The effects of cranberry juice consumption on antioxidant status and biomarkers relating to heart disease and cancer in healthy human volunteers.

Posted: November 2, 2010
Authors: Duthie SJ, Jenkinson AM, Crozier A, Mullen W, Pirie L, Kyle J, Yap LS, Christen P, Duthie GG
Journal: Eur J Nutr 45(2):113-22

Abstract: BACKGROUND: Consumption of fruit and vegetables is associated with a decreased risk of heart disease and cancer. This has been ascribed in part to antioxidants in these foods inactivating reactive oxygen species involved in initiation or progression of these diseases. Non-nutritive anthocyanins are present in significant amounts in the human diet. However, it is unclear whether they have health benefits in humans.

AIM: To determine whether daily consumption of anthocyanin-rich cranberry juice could alter plasma antioxidant activity and biomarkers of oxidative stress.

METHODS: 20 healthy female volunteers aged 18-40 y were recruited. Subjects consumed 750 ml/day of either cranberry juice or a placebo drink for 2 weeks. Fasted blood and urine samples were obtained over 4 weeks. The total phenol, anthocyanin and catechin content of the supplements and plasma were measured. Anthocyanin glycosides were identified by tandem mass spectrometry (MS-MS). Vitamin C, homocysteine (tHcy) and reduced glutathione (GSH) were measured by HPLC. Total antioxidant ability was determined using electron spin resonance (ESR) spectrometry and by the FRAP assay. Plasma total cholesterol, high density lipoprotein (HDL), and low density lipoprotein (LDL) cholesterol and triglycerides (TG) were measured. Glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD) activities were measured in erythrocytes. Urine was collected for analysis of malondialdehyde (MDA) by HPLC and 8-oxo-deoxyguanosine (8-oxo-dG) by ELISA. Endogenous and induced DNA damage were measured by single cell gel electrophoresis (SCGE) in lymphocytes.

RESULTS: Vitamin C, total phenol, anthocyanin and catechin concentrations and FRAP and ESR values were significantly higher in the cranberry juice compared with the placebo. Cyanidin and peonidin glycosides comprised the major anthocyanin metabolites [peonidin galactoside (29.2%) > cyanidin arabinoside (26.1%) > cyanidin galactoside (21.7%) > peonidin arabinoside (17.5%) > peonidin glucoside (4.1%) > cyanidin glucoside (1.4 %)]. Plasma vitamin C increased significantly (P<0.01) in volunteers consuming cranberry juice. No anthocyanins (plasma) or catechins (plasma or urine) were detectable and plasma total phenols, tHcy,TC,TG,HDL and LDL were unchanged. The antioxidant potential of the plasma, GSH-Px, CAT and SOD activities, and MDA were similar for both groups. Supplementation with cranberry juice did not affect 8-oxo-deoxyguanosine in urine or endogenous or H(2)O(2)-induced DNA damage in lymphocytes.

CONCLUSIONS: Cranberry juice consumption did not alter blood or cellular antioxidant status or several biomarkers of lipid status pertinent to heart disease. Similarly, cranberry juice had no effect on basal or induced oxidative DNA damage. These results show the importance of distinguishing between the in vitro and in vivo antioxidant activities of dietary anthocyanins in relation to human health.

The warfarin-cranberry juice interaction revisited: A systematic in vitro-in vivo evaluation

Posted: November 2, 2010
Authors: Ngo N, Brantley SJ, Carrizosa DR, Kashuba AD, Dees EC, Kroll DJ, Oberlies NH, Paine MF
Journal: J Exp Pharmacol 2010(2):83-91

Abstract: BACKGROUND: Cranberry products have been implicated in several case reports to enhance the anticoagulant effect of warfarin. The mechanism could involve inhibition of the hepatic CYP2C9-mediated metabolic clearance of warfarin by components in cranberry. Because dietary/natural substances vary substantially in bioactive ingredient composition, multiple cranberry products were evaluated in vitro before testing this hypothesis in vivo. METHODS: The inhibitory effects of five types of cranberry juices were compared with those of water on CYP2C9 activity (S-warfarin 7-hydroxylation) in human liver microsomes (HLM). The most potent juice was compared with water on S/R-warfarin pharmacokinetics in 16 healthy participants given a single dose of warfarin 10 mg. RESULTS: Only one juice inhibited S-warfarin 7-hydroxylation in HLM in a concentration-dependent manner (P < 0.05), from 20% to >95% at 0.05% to 0.5% juice (v/v), respectively. However, this juice had no effect on the geometric mean AUC(0-∞) and terminal half-life of S/R-warfarin in human subjects. CONCLUSIONS: A cranberry juice that inhibited warfarin metabolism in HLM had no effect on warfarin clearance in healthy participants. The lack of an in vitro-in vivo concordance likely reflects the fact that the site of warfarin metabolism (liver) is remote from the site of exposure to the inhibitory components in the cranberry juice (intestine).

Consumption of sweetened dried cranberries versus unsweetened raisins for inhibition of uropathogenic Escherichia coli adhesion in human urine: a pilot study

Posted: November 1, 2010
Authors: Greenberg JA, Newmann SJ and Howell AB
Journal: J Altern Complement Med 11(5):875-8

Abstract: OBJECTIVES: The aim of this study was to determine whether consumption of sweetened dried cranberries elicits urinary anti-adherence properties against Escherichia coli as previously demonstrated with cranberry juice and/or sweetened cranberry juice cocktail, compared to unsweetened raisins.

DESIGN: Uropathogenic E. coli isolates were obtained from five women with culture-confirmed urinary tract infections (UTIs). Four urine samples were collected from each subject. The first urine sample was collected before any study intervention. The second urine sample was collected 2-5 hours after consumption of one box (42.5 g) of raisins. The third urine sample was collected 5-7 days later. The final urine sample was collected 2-5 hours after consumption of approximately 42.5 g of dried cranberries.

MATERIALS AND METHODS: E. coli isolates were incubated separately in each of the four urine samples collected from the five subjects. Bacteria were harvested from the urine and tested for the ability to prevent adhesion of P-fimbriated E. coli bacteria using a mannose-resistant hemagglutination assay with human red blood cells (A1, Rh+).

RESULTS: Of the urine samples collected after dried cranberry consumption, one demonstrated 50% antiadherence activity, two demonstrated 25% activity, and two did not show any increased activity. None of the control urine samples and none of the postraisin consumption samples demonstrated any inhibitory activity.

CONCLUSIONS: Data from this pilot study on only five subjects suggest that consumption of a single serving of sweetened dried cranberries may elicit bacterial antiadhesion activity in human urine, whereas consumption of a single serving of raisins does not. Further studies are needed to verify the antiadhesion effect of sweetened dried cranberries. In addition, dose-response and pharmacokinetics of the active compounds in the dried cranberries need to be determined. If clinical research is positive, dried cranberries could potentially be a viable alternative to cranberry juice consumption for prevention of UTIs.

Cranberry or trimethoprim for the prevention of recurrent urinary tract infections? a randomized controlled trial in older women

Posted: November 1, 2010
Authors: McMurdo ME, Argo I, Phillips G, Daly F, Davey P
Journal: J Antimicrob Chemother 63(2):389-95

Abstract: OBJECTIVES: To compare the effectiveness of cranberry extract with low-dose trimethoprim in the prevention of recurrent urinary tract infections (UTIs) in older women.

PATIENTS AND METHODS: One hundred and thirty-seven women with two or more antibiotic-treated UTIs in the previous 12 months were randomized to receive either 500 mg of cranberry extract or 100 mg of trimethoprim for 6 months.

RESULTS: Thirty-nine of 137 participants (28%) had an antibiotic-treated UTI (25 in the cranberry group and 14 in the trimethoprim group); difference in proportions relative risk 1.616 (95% CI: 0.93, 2.79) P = 0.084. The time to first recurrence of UTI was not significantly different between the groups (P = 0.100). The median time to recurrence of UTI was 84.5 days for the cranberry group and 91 days for the trimethoprim group (U = 166, P = 0.479). There were 17/137 (12%) withdrawals from the study, 6/69 (9%) from the cranberry group and 11/68 (16%) from the trimethoprim group (P = 0.205), with a relative risk of withdrawal from the cranberry group of 0.54 (95% CI: 0.19, 1.37).

CONCLUSIONS: Trimethoprim had a very limited advantage over cranberry extract in the prevention of recurrent UTIs in older women and had more adverse effects. Our findings will allow older women with recurrent UTIs to weigh up with their clinicians the inherent attractions of a cheap, natural product like cranberry extract whose use does not carry the risk of antimicrobial resistance or super-infection with Clostridium difficile or fungi.

Dosage effect on uropathogenic escherichia coli anti-adhesion activity in urine following consumption of cranberry powder standardized for proanthocyanidin content: a multicentric randomized double blind study

Posted: November 1, 2010
Authors: Howell AB, Botto H, Combescure C, Blanc-Potard A-B, Gausa L, Matsumoto T, Tenke P, Sotto A, Lavigne JP
Journal: BMC Infect Dis 10:94

Abstract: BACKGROUND: Ingestion of cranberry (Vaccinium macrocarpon Ait.) has traditionally been utilized for prevention of urinary tract infections. The proanthocyanidins (PACs) in cranberry, in particular the A-type linkages have been implicated as important inhibitors of primarily P-fimbriated E. coli adhesion to uroepithelial cells. Additional experiments were required to investigate the persistence in urine samples over a broader time period, to determine the most effective dose per day and to determine if the urinary anti-adhesion effect following cranberry is detected within volunteers of different origins.

METHODS: Two separate bioassays (a mannose-resistant hemagglutination assay and an original new human T24 epithelial cell-line assay) have assessed the ex-vivo urinary bacterial anti-adhesion activity on urines samples collected from 32 volunteers from Japan, Hungary, Spain and France in a randomized, double-blind versus placebo study. An in vivo Caenorhabditis elegans model was used to evaluate the influence of cranberry regimen on the virulence of E. coli strain.

RESULTS: The results indicated a significant bacterial anti-adhesion activity in urine samples collected from volunteers that consumed cranberry powder compared to placebo (p < 0.001). This inhibition was clearly dose-dependent, prolonged (until 24 h with 72 mg of PAC) and increasing with the amount of PAC equivalents consumed in each cranberry powder regimen. An in vivo Caenorhabditis elegans model showed that cranberry acted against bacterial virulence: E. coli strain presented a reduced ability to kill worms after a growth in urines samples of patients who took cranberry capsules. This effect is particularly important with the regimen of 72 mg of PAC.

CONCLUSIONS: Administration of PAC-standardized cranberry powder at dosages containing 72 mg of PAC per day may offer some protection against bacterial adhesion and virulence in the urinary tract. This effect may offer a nyctohemeral protection.

Interaction of flurbiprofen with cranberry juice, grape juice, tea, and fluconazole: in vitro and clinical studies

Posted: November 1, 2010
Authors: Greenblatt DJ, von Moltke LL, Perloff ES, Luo Y, Harmatz JS, Zinny MA
Journal: Clin Pharmacol Ther 79(1):125-33

Abstract: OBJECTIVES: Recent anecdotal, unvalidated case reports have suggested potentiation of warfarin-induced anticoagulation by cranberry juice, possibly through inhibition of human cytochrome P450 (CYP) 2C9, the enzyme responsible for the clearance of the active S-enantiomer of warfarin. To address this question, the effect of cranberry juice and other beverages on CYP2C9 activity was evaluated in vitro and in vivo.

METHODS: The effects of 4 beverages on CYP2C9 activity were studied in human liver microsomes, by use of flurbiprofen hydroxylation as the index reaction. In a clinical study 14 healthy volunteers received 100 mg flurbiprofen on 5 occasions in a crossover fashion, with at least 1 week separating the 5 trials. Flurbiprofen was preceded in random sequence by the following: (1) cranberry juice placebo (8 oz), (2) cranberry juice (8 oz), (3) brewed tea (8 oz), (4) grape juice (8 oz), and (5) fluconazole, a CYP2C9 inhibitor serving as a positive control, with 8 oz of water.

RESULTS: Flubiprofen hydroxylation in vitro was reduced to 11% +/- 8% of control by 2.5% (vol/vol) brewed tea, to 10% +/- 7% of control by grape juice, to 56% +/- 16% of control by cranberry juice, to 85% +/- 5% of control by cranberry juice placebo, and to 21% +/- 6% of control by the index inhibitor sulfaphenazole (2.5 micromol/L) (P <.01 for all comparisons versus control). Flurbiprofen clearance (29-33 mL/min) and elimination half-life (3.3-3.4 hours) did not differ significantly among trials 1, 2, 3, and 4. However, clearance in the fluconazole treatment condition (trial 5) was significantly reduced compared with the placebo control (17 +/- 5 mL/min versus 31 +/- 8 mL/min, P <.05), and the half-life was prolonged (5.3 +/- 1.6 hours versus 3.3 +/- 0.8 hours, P <.05). Formation of 4-hydroxyflurbiprofen was correspondingly reduced by fluconazole (P <.05).

CONCLUSIONS: Although grape juice and tea impaired CYP2C9 activity in vitro, none of the 3 beverages altered CYP2C9-mediated clearance of flurbiprofen in humans, making a pharmacokinetic interaction with warfarin highly unlikely.

Predictors of urinary tract infection after menopause: a prospective study

Posted: November 1, 2010
Authors: Jackson SL, Boyko EJ, Scholes D, Abraham L, Gupta K, Fihn SD
Journal: Am J Med 117(12):903-911

Abstract: Purpose: To describe the incidence of and risk factors for acute cystitis among nondiabetic and diabetic postmenopausal women.
Methods:We conducted a population-based, prospective cohort study of 1017 postmenopausal women, aged 55 to 75 years, who were enrolled in a health maintenance organization and followed for 2 years. A wide range of behavioral and physiologic exposures were assessed at baseline interview and follow-up clinic visits; the main outcome measure was microbiologically confirmed acute symptomatic cystitis. Follow-up was 87% at 12 months and 81% at 24 months.
Results:During 1773 person-years of follow-up, 138 symptomatic urinary tract infections occurred (incidence, 0.07 per person-year). Independent predictors of infection included insulin-treated diabetes (hazard ratio [HR] = 3.4; 95% confidence interval [CI]: 1.7 to 7.0) and a lifetime history of urinary tract infection (HR for six or more infections = 6.9; 95% CI: 3.5 to 13.6). Borderline associations included a history of vaginal estrogen cream use in the last month (HR = 1.8; 95% CI: 1.0 to 3.4), a history of kidney stones (HR = 1.9; 95% CI: 1.0 to 3.7), and asymptomatic bacteriuria at baseline (HR = 1.8; 95% CI: 0.9 to 3.5). Sexual activity, urinary incontinence, parity, postcoital urination, vaginal dryness, use of cranberry juice, vaginal bacterial flora, and postvoid residual bladder volume were not associated with incident acute cystitis after multivariable adjustment.
Conclusion:Insulin-treated diabetes is a potentially modifiable risk factor for incident acute cystitis among postmenopausal women, whereas a lifetime history of urinary tract infection was the strongest predictor. Use of oral or vaginal estrogen was not protective, and a wide range of behavioral and physiologic factors was not associated with acute cystitis episodes in this generally healthy sample.

The effect of cranberry juice and cranberry proanthocyanidins on the infectivity of human enteric viral surrogates.

Posted: November 1, 2010
Authors: Su X, Howell AB, D'Souza DH
Journal: Food Microbiol 27(4):535-40

Abstract: The effect of cranberry juice (CJ) and cranberry proanthocyanidins (PAC) on the infectivity of human enteric virus surrogates, murine norovirus (MNV-1), feline calicivirus (FCV-F9), MS2(ssRNA) bacteriophage, and phiX-174(ssDNA) bacteriophage was studied. Viruses at high (approximately 7 log(10) PFU/ml) or low (approximately 5 log(10) PFU/ml) titers were mixed with equal volumes of CJ, 0.30, 0.60, and 1.20 mg/ml final PAC concentration, or water and incubated for 1 h at room temperature. Viral infectivity after treatments was evaluated using standardized plaque assays. At low viral titers, FCV-F9 was undetectable after exposure to CJ or the three tested PAC solutions. MNV-1 was reduced by 2.06 log(10) PFU/ml with CJ, and 2.63, 2.75, and 2.95 log(10) PFU/ml with 0.15, 0.30, and 0.60 mg/ml PAC, respectively. MS2 titers were reduced by 1.14 log(10) PFU/ml with CJ, and 0.55, 0.80, and 0.96 log(10) PFU/ml with 0.15, 0.30, and 0.60 mg/ml PAC, respectively. phi-X174 titers were reduced by 1.79 log(10) PFU/ml with CJ, and 1.95, 3.67, and 4.98 log(10) PFU/ml with PAC at 0.15, 0.30, and 0.60 mg/ml, respectively. Experiments using high titers showed similar trends but with decreased effects. CJ and PAC show promise as natural antivirals that could potentially be exploited for foodborne viral illness treatment and prevention.

A double-blinded, placebo-controlled, randomized trial of the neuropsychologic efficacy of cranberry juice in a sample of cognitively intact older adults: pilot study findings

Posted: October 31, 2010
Authors: Crews WD Jr, Harrison DW, Griffin ML, Addison K, Yount AM, Giovenco MA and Hazell J.
Journal: J Altern Complement Med 11(2):305-9

Abstract: OBJECTIVES: The aim of this research was to conduct the first known clinical trial of the short-term (i.e., 6 weeks) efficacy of cranberry juice on the neuropsychologic functioning of cognitively intact older adults.PARTICIPANTS: Fifty (50) community-dwelling, cognitively intact volunteers, > or = 60 years old, who reported no history of dementia or significant neurocognitive impairments, participated in this study.DESIGN: A 6-week, double-blind, placebo-controlled, randomized, parallel-group, clinical trial was utilized. Participants were randomly assigned to receive either 32 ounces/day of a beverage containing 27% cranberry juice per volume (n = 25) or placebo (n = 25) for 6 weeks, and administered a series of neuropsychologic tests at both pretreatment baseline and again after 6 weeks of either cranberry juice or placebo treatment to assess treatment-related changes.OUTCOME MEASURES: Efficacy measures consisted of participants' raw scores on the following standardized neuropsychologic tests: Selective Reminding Test, Wechsler Memory Scale-III Faces I and Faces II subtests, Trail Making Test (Parts A and B), Stroop Color and Word Test, and the Wechsler Adult Intelligence Scale- III Digit Symbol-Coding subtest. A subjective Follow-up Self-report Questionnaire was also administered to participants at the conclusion of the end-of-treatment phase assessments.RESULTS: Two-factor, mixed analyses of variance (ANOVA) revealed no significant group (cranberry juice and placebo) by trial (pretreatment baseline and end-of-treatment assessments) interactions across all of the neuropsychologic tests and measures utilized in this study when a Bonferroni corrected alpha level was used to correct for multiple comparisons (i.e., .05/17 group by trial comparisons = .003). Pearson Chi-Square analyses of the groups' self-reported changes over the 6-week treatment phase in their abilities to remember, thinking processes, moods, energy levels, and overall health on the Follow-up Self-report Questionnaire revealed no significant relationships. However, a nonsignificant trend (X2(1) = 2.373, p = 0.123) was noted for participants' self-reported overall abilities to remember from pretreatment baseline to the end-of-treatment assessment. Specifically, more than twice as many participants in the cranberry group (n = 9, 37.5%) rated their overall abilities to remember by treatment end as "improved" as compared to placebo controls (n = 4, 17.4%).CONCLUSIONS: Taken together, no significant interactions were found between the cranberry and placebo groups and their pretreatment baseline and end-of-treatment phase (after 6 weeks) standardized neuropsychologic assessments. A nonsignificant trend was noted, however, on a subjective, self-report questionnaire where twice as many participants in the cranberry group rated their overall abilities to remember by treatment end as "improved" compared to placebo controls.

Comparison of urinary cytokines after ingestion of cranberry juice cocktail in pregnant subjects: a pilot study.

Posted: October 31, 2010
Authors: Wing DA, Rumney PJ, Leu SY, Zaldivar F
Journal: Am J Perinatol 27(2):137-42

Abstract: Our objective was to evaluate urinary cytokine excretion after daily cranberry or placebo exposure in pregnant women. Four-hour urine samples were collected from 27 pregnant women subjects who were randomized to cranberry juice cocktail or placebo in three treatment arms: A: Cranberry (C) two times daily (C, C; n = 10 pregnant); B: cranberry in the AM, then placebo (P) in the PM (C, P; n = 9 pregnant); and C: placebo two times daily (P, P; n = 8 pregnant). Urinary cytokines were measured using commercially available kits. There was a statistically significant difference in interleukin (IL)-6 of the urinary cytokines between the multiple daily cranberry dosing group (group A [C, C]): median, 3.16 (range, 0.01 to 7.34) and the placebo group (group C [P, P]): 9.32 (0.53 to 29.61 pg/mL; p = 0.038, Kruskal-Wallis test). We concluded that a difference in IL-6 was found in the multiple daily cranberry dosing groups compared with placebo. Lack of differences based on treatment allocation in the other cytokines may be due to beta error. Further studies are planned to evaluate these assays for the assessment of clinical effect.

Cranberry juice and adhesion of antibiotic-resistant uropathogens

Posted: October 31, 2010
Authors: Howell AB and Foxman B
Journal: JAMA 287(23):3082-3

Abstract: No abstract - Introduction: Urinary tract infections (UTIs) account for more than 11 million physician visits annually in the United States and have become increasingly resistant to first-line antibiotic therapy. Recent evidence suggests that consumption of cranberry juice beverages is effective at preventing UTIs, although further studies are needed to validate potential treatment effects. While early research focused on a mechanism of urinary acidification, the largest clinical trial to date found no evidence to support this. Recent studies suggest that cranberry proanthocyanidins (condensed tannins) may inhibit P-fimbriated Escherichia coli from adhering to uroepithelial cells, the initial step in development of UTI. The effectiveness of cranberry proanthocyanidins and cranberry beverages against antibiotic-resistant E coli, however, has not been previously tested. We assessed whether consumption of cranberry juice cocktail prevents adhesion of antibiotic-resistant uropathogenic P-fimbriated E coli to the uroepithelium.

Cranberry juice and bacterial colonization in children--a placebo-controlled randomized trial

Posted: October 31, 2010
Authors: Kontiokari T, Salo J, Eerola E and Uhari M
Journal: Clin Nutr 24(6):1065-72

Abstract: BACKGROUND: The cranberry produces antimicrobial compounds such as proanthocyanidines in response to microbial invasion. In vitro it is able to prevent growth, adhesion or biofilm formation of a large number of bacteria, while clinically, cranberry juice has been shown to prevent urinary tract infections (UTI) in women. However, the effect of cranberry on bacterial colonization more widely has not been evaluated. We were interested in studying cranberry juice in children since many children with recurrent UTI need long-term antimicrobial prophylaxis and would benefit from an alternative. OBJECTIVE: To evaluate the effect of cranberry juice on nasopharyngeal and colonic bacterial flora, to evaluate how well cranberry juice is accepted by children and to evaluate its effect on infectious diseases and related symptoms. DESIGN: Children (mean age 4.3 years) in day care centers were randomized to receive either cranberry juice (n=171) or a placebo (n=170) for 3 months. Bacterial samples were collected before and after the intervention and analyzed for both respiratory bacterial pathogens and enteric fatty acid composition, reflecting changes in the colonic bacterial flora. Infectious diseases and their symptoms were monitored using symptom diaries. Compliance was evaluated as the number of drop-outs during the trial and by counting the numbers of doses taken. RESULTS: The carriage of respiratory bacteria did not change significantly during the intervention, while fecal fatty acid composition changed significantly with time (P<0.001) but did not differ between the groups (P>0.05). Cranberry juice had no effect on common infectious diseases or their symptoms. The cranberry juice was well accepted: the number of drop-outs in 3 months was 18 (11%) in the cranberry group and 11 (7%) in the placebo group, and most of the doses were taken as instructed, 145 (88%) and 129 (77%) children, respectively, taking at least 90% of the doses. CONCLUSIONS: Cranberry juice was well accepted by the children, but led to no change in either the bacterial flora in the nasopharynx or the bacterial fatty acid composition of stools. Thus cranberries seem to have beneficial effect on urinary health only and this is not compromised by other unexpected antimicrobial effects.

Cranberry juice induces nitric oxide-dependent vasodilation in vitro and its infusion transiently reduces blood pressure in anesthetized rats

Posted: October 31, 2010
Authors: Maher MA, Mataczynski H, Stefaniak HM and Wilson T
Journal: J Med Food 3(3):141-7

Abstract: ABSTRACT Red wine vasodilates rat aortae, an effect attributed to polyphenolic compounds. Cranberry juice (CBJ) is also rich in polyphenols. We determined that CBJ has vasorelaxing properties similar to those of red wine. Rat aortic rings cleaned in Krebs buffer, pH 7.4, bubbled with 95% O(2) and 5% CO(2) were recovered for 30 minutes at 37 degrees C under 2.0 g tension. After phenylephrine (PE, 100 mumol/L) contraction, acetylcholine (3 mumol/L)-induced relaxation of intact vessel was significantly higher than in denuded vessels (59.1 +/- 0.27% versus 10.1 +/- 0.09% of the maximal PE contraction; P <.003). After a second PE contraction, a 1:100 dilution of CBJ was added. Intact rings were vasodilated by CBJ with 56.7 +/- 0.26% relaxation, compared to denuded rings with 8.9 +/- 0.06% relaxation (P <.002). Addition of L-NAME reversed CBJ-induced vasorelaxation in intact vessels with 0.54 +/- 0.34 g compared to 0.04 +/- 0.04 g in denuded vessels (P <.007). Subsequent addition of L-arginine resulted in a return of vasodilation in intact vessels. Additionally, CBJ infusion at a 1:100 dilution of estimated blood volume resulted in a 16% reduction of mean arterial blood pressure in anesthetized rats. This study suggests that, like red wine, CBJ has the capacity to exert in vitro and in vivo vasodilatory effects.

Does ingestion of cranberry juice reduce symptomatic urinary tract infections in older people in hospital? A double-blind, placebo-controlled trial.

Posted: October 31, 2010
Authors: McMurdo ME, Bissett LY, Price RJ, Phillips G and Crombie IK
Journal: Age Aging 34(3):256-61

Abstract: Background: cranberry juice is often given to older people in hospital to prevent urinary tract infection (UTI), although
there is little evidence to support its use.
Objective: to assess whether cranberry juice ingestion is effective in reducing UTIs in older people in hospital.
Design: randomised, placebo-controlled, double-blind trial.
Setting: Medicine for the Elderly assessment and rehabilitation hospital wards.
Subjects: 376 older patients in hospital.
Methods: participants were randomised to daily ingestion of 300 ml of cranberry juice or matching placebo beverage. The primary outcome was time to onset of first UTI. Secondary outcomes were adherence to beverage drinking, courses of antibiotics prescribed, and organisms responsible for UTIs.
Results: a total of 21/376 (5.6%) participants developed a symptomatic UTI: 14/189 in the placebo group and 7/187 in the cranberry juice group. These between-group differences were not significant, relative risk (RR) 0.51 [95% CI 0.21–1.22, P = 0.122). Although there were significantly fewer infections with Escherichia coli in the cranberry group (13 versus 4) RR 0.31 [95% CI 0.10–0.94, P =0.027], this should be interpreted with caution as it was a secondary outcome.
Conclusion: despite having the largest sample size of any clinical trial yet to have examined the effect of cranberry juice ingestion, the actual infection rate observed was lower than anticipated, making the study underpowered. This study has confirmed the acceptability of cranberry juice to older people. Larger trials are now required to determine whether it is effective in reducing UTIs in older hospital patients.

Inhibitory effect of cranberry polyphenol on cariogenic bacteria

Posted: October 31, 2010
Authors: Yamanaka-Okada A, Sato E, Kouchi T, Kimizuka R, Kato T, Okuda K
Journal: Bull Tokyo Dent Coll 49(3):107-12

Abstract: The purpose of this study was to investigate the effect of cranberry polyphenol fraction on mutans streptococci. Hydrophobicity is an important factor in the adherence of bacteria to the tooth surface. We found that cranberry polyphenol fraction significantly decreased the hydrophobicity of Streptococcus sobrinus 6715, Streptococcus mutans MT8148R and JC2 in a dose-dependent manner (p<0.05). Biofilm formation by S. sobrinus 6715 and S. mutans MT8148R was inhibited by 100 microg/ml cranberry polyphenol fraction (p<0.01). When dosage was increased to 500 microg/ml, biofilm formation by S. mutans JC2 was significantly inhibited (p<0.05). Addition of 500 microg/ml cranberry polyphenol fraction to medium inhibited growth of S. mutans MT8148R compared with the control (p<0.05).

Modulation of Helicobacter pylori colonization with cranberry juice and Lactobacillus johnsonii La1 in children

Posted: October 31, 2010
Authors: Gotteland M, Andrews M, Toledo M, Munoz L, Caceres P, Anziani A, Wittig E, Speisky H, Salazar G.
Journal: Nutrition 24(5):421-426

Abstract: OBJECTIVE: Probiotics and cranberry have been shown to inhibit Helicobacter pylori in vitro owing to bacteriocin production and high levels of proanthocyanidins, respectively. These effects have been confirmed in clinical trials with H. pylori-positive subjects. The aim of this study was to evaluate whether regular intake of cranberry juice and the probiotic Lactobacillus johnsonii La1 (La1) may result in an additive or synergistic inhibition of H. pylori in colonized children.METHODS: A multicentric, randomized, controlled, double-blind trial was carried out in 295 asymptomatic children (6-16 y of age) who tested positive for H. pylori by (13)C-urea breath test (UBT). Subjects were allocated in four groups: cranberry juice/La1 (CB/La1), placebo juice/La1 (La1), cranberry juice/heat-killed La1 (CB), and placebo juice/heat-killed La1 (control). Cranberry juice (200 mL) and La1 product (80 mL) were given daily for 3 wk, after which a second UBT was carried out. A third UBT was done after a 1-mo washout in those children who tested negative in the second UBT.RESULTS: Two hundred seventy-one children completed the treatment period (dropout 8.1%). Helicobacter pylori eradication rates significantly differed in the four groups: 1.5% in the control group compared with 14.9%, 16.9%, and 22.9% in the La1, CB, and CB/La1 groups, respectively (P < 0.01); the latter group showed a slight but not significant increase when compared with the other treated groups. The third UBT was carried out only in 19 of the 38 children who tested negative in the second UBT and H. pylori was detected in 80% of them.CONCLUSION: These results suggest that regular intake of cranberry juice or La1 may be useful in the management of asymptomatic children colonized by H. pylori; however, no synergistic inhibitory effects on H. pylori colonization were observed when both foodstuffs were simultaneously consumed.

Randomised trial of cranberry-lingonberry juice and Lactobacillus GG drink for the prevention of urinary tract infections in women

Posted: October 31, 2010
Authors: Kontiokari T, Sundqvist K, Nuutinen M, Pokka T, Koskela M and Uhari M
Journal: BMJ 322(7302):1571

Abstract: OBJECTIVE: To determine whether recurrences of urinary tract infection can be prevented with cranberry-lingonberry juice or with Lactobacillus GG drink. Design: Open, randomised controlled 12 month follow up trial.

SETTING: Health centres for university students and staff of university hospital.

PARTICIPANTS: 150 women with urinary tract infection caused by Escherichia coli randomly allocated into three groups. Interventions: 50 ml of cranberry-lingonberry juice concentrate daily for six months or 100 ml of lactobacillus drink five days a week for one year, or no intervention. Main outcome measure: First recurrence of symptomatic urinary tract infection, defined as bacterial growth >/=10(5 )colony forming units/ml in a clean voided midstream urine specimen.

RESULTS: The cumulative rate of first recurrence of urinary tract infection during the 12 month follow up differed significantly between the groups (P=0.048). At six months, eight (16%) women in the cranberry group, 19 (39%) in the lactobacillus group, and 18 (36%) in the control group had had at least one recurrence. This is a 20% reduction in absolute risk in the cranberry group compared with the control group (95% confidence interval 3% to 36%, P=0.023, number needed to treat=5, 95% confidence interval 3 to 34).

CONCLUSION: Regular drinking of cranberry juice but not lactobacillus seems to reduce the recurrence of urinary tract infection.

Reduction of Escherichia coli adherence to uroepithelial bladder cells after consumption of cranberry juice: a double-blind randomized placebo-controlled cross-over trial

Posted: October 31, 2010
Authors: Di Martino P, Agniel R, David K, Templer C, Gaillard JL, Denys P, Botto H
Journal: World J Urol 24(1):21-7

Abstract: To determine the efficacy of the consumption of cranberry juice versus placebo with regard to the presence of in vitro bacterial anti-adherence activity in the urine of healthy volunteers. Twenty healthy volunteers, 10 men and 10 women, were included. The study was a double-blind, randomized, placebo-controlled, and cross-over study. In addition to normal diet, each volunteer received at dinner a single dose of 750 ml of a total drink composed of: (1) 250 ml of the placebo and 500 ml of mineral water, or (2) 750 ml of the placebo, or (3) 250 ml of the cranberry juice and 500 ml of mineral water, or (4) 750 ml of the cranberry juice. Each volunteer took the four regimens successively in a randomly order, with a washout period of at least 6 days between every change in regimen. The first urine of the morning following cranberry or placebo consumption was collected and used to support bacterial growth. Six uropathogenic Escherichia coli strains (all expressing type 1 pili; three positive for the gene marker for P-fimbriae papC and three negative for papC), previously isolated from patients with symptomatic urinary tract infections, were grown in urine samples and tested for their ability to adhere to the T24 bladder cell line in vitro. There were no significant differences in the pH or specific gravity between the urine samples collected after cranberry or placebo consumption. We observed a dose dependent significant decrease in bacterial adherence associated with cranberry consumption. Adherence inhibition was observed independently from the presence of genes encoding type P pili and antibiotic resistance phenotypes. Cranberry juice consumption provides significant anti-adherence activity against different E. coli uropathogenic strains in the urine compared with placebo.

Favorable glycemic response of type 2 diabetics to low-calorie cranberry juice

Posted: October 30, 2010
Authors: Wilson T, Meyers SL, Singh AP, Limburg PJ and Vorsa N
Journal: J Food Sci 73(9):H241-5

Abstract: Fruit and vegetable intake is typically low for type 2 diabetics, possibly due to a perceived adverse effect on glycemic control. Cranberry juice (CBJ) may represent an attractive means for increasing fruit intake and simultaneously affording positive health benefits. This single cross-over design compared metabolic responses of type 2 diabetics (n= 12) to unsweetened low-calorie CBJ (LCCBJ; 19 Cal/240 mL), carbohydrate sweetened normal calorie CBJ (NCCBJ; 120 Cal/240 mL), isocaloric low-calorie sugar water control (LCC), and isocaloric normal calorie sugar water control (NCC) interventions. CBJ flavonols and anthocyanins, and proanthocyanidins were quantified with HPLC, LC-MS, and MALDI-TOF that includes an original characterization of several large oligomeric proanthocyanidins. Blood glucose peaked 30 min postingestion after NCCBJ and NCC at 13.3 +/- 0.5 and 12.8 +/- 0.9 (mmol/L), and these responses were significantly greater than the LCCBJ and LCC peaks of 8.1 +/- 0.5 and 8.7 +/- 0.5, respectively. Differences in glycemic response remained significant 60 min, but not 120 min postingestion. Plasma insulin values 60 min postingestion for NCCBJ and NCC interventions were 140 +/- 19 and 151 +/- 18 (pmol/L), respectively, and significantly greater than the LCCBJ and LCC values of 56 +/- 10 and 54 +/- 10; differences were not significant 120 min postingestion. Metabolic responses within the 2 high and 2 low-calorie beverages were virtually identical; however, exposure to potentially beneficial nutrients was greater with CBJ. Relative to conventionally sweetened preparation, LCCBJ provides a favorable metabolic response and should be useful for promoting increased fruit consumption among type 2 diabetics or others wishing to limit carbohydrate intake.

Cranberry is not effective for the prevention or treatment of urinary tract infections in individuals with spinal cord injury.

Posted: October 28, 2010
Authors: Opperman EA
Journal: Spinal Cord 48(6):451-6

Abstract: STUDY DESIGN: Literature review. OBJECTIVES: Urinary tract infections (UTIs) are the most common medical complication experienced by individuals with spinal cord injury (SCI). Recent research presents conflicting evidence regarding use of cranberry in reducing growth and colonization of uroepithelial cells by uropathogenic bacteria. The objective was to determine whether the literature supports the use of cranberry in preventing or treating UTIs in the SCI population. METHODS: MEDLINE was searched for intervention studies, which investigated the use of cranberry in the prevention or treatment of UTIs in the SCI population. If the studies met the inclusion criteria, full articles were located and reviewed. RESULTS: Five studies (four randomized clinical control-three trials using cranberry tablets vs placebos and one using cranberry juice-and one pilot study using cranberry juice) were identified which evaluated the effectiveness of cranberry products for the prevention or treatment of UTIs in the SCI population. Three studies reported no statistically significant effect of cranberry tablets in urinary pH, urinary bacterial count, urinary white blood cell (WBC) count, urinary bacterial, and WBC counts in combination or episodes of symptomatic UTIs. A fourth study showed that cranberry juice intake significantly reduced biofilm load compared with baseline. A final study reported fewer UTIs during the period with cranberry extract tablets vs placebo. CONCLUSIONS: Limited evidence from clinical trials that vary in design suggests that cranberry, in juice or supplement form, does not seem to be effective in preventing or treating UTIs in the SCI population. More rigorous clinical research is needed to confirm this.

Cranberry juice and urinary tract infections: is there a beneficial relationship

Posted: October 28, 2010
Authors: Kuzminski LN
Journal: Nutr Rev 54(11 Pt 2):S87-90

Abstract: No abstract - Conclusion:
Science often causes us to disregard the validity of folklore
treatments for common medical conditions. However,
those folklore practices that retain a persistent consumer
and practitioner following over time merit rigorous scientific scrutiny. Approaches such as those described here
regarding UTI risk reduction by cranberry juice could serve
as a model to clarify the potential functional food role of
Cranberry juice in treating and preventing UTIs.

Cranberry juice for prophylaxis of urinary tract infections – conclusions from clinical experience and research

Posted: October 19, 2010
Authors: Nowack R, Schmidt W
Journal: Phytomedicine 15(9):653-667

Abstract: Cranberry juice (Vaccinium macrocarpon) is a widely used and recommended North-American folk remedy for prophylaxis of urinary tract infections (UTI). Clinical trials have documented its efficacy in women with recurrent UTI, but so far not in other groups of patients. The composition of effective cranberry products and its dosage in UTI prophylaxis have not been defined. Intriguing experimental research has identified an anti-adhesive mechanism of cranberry juice that prevents docking of bacteria on host tissues. This efficacy mechanism can be traced in patients' urine following oral intake of cranberry products and appears to be due to proanthocyanidins with an A-type linkage of flavanols. The application of this anti-adhesion mechanism of cranberry-proanthocyandins is currently also investigated in other common diseases of bacterial pathogenesis, for example Helicobacter pylori-associated gastritis and dental caries/periodontal disease. The use of cranberry products appears to be safe and provide additional benefits by anti-oxidant and cholesterol-lowering activity.

The absence of an interaction between warfarin and cranberry juice: a randomized, double-blind trial.

Posted: October 19, 2010
Authors: Ansell J, McDonough M, Zhao Y, Harmatz JS, Greenblatt DJ.
Journal: J Clin Pharmacol 49(7):824-30

Abstract: The question of potentiation of warfarin anticoagulation by cranberry juice (CJ) is a topic of biomedical importance. Anecdotal reports of CJ-warfarin interaction are largely unconfirmed in controlled studies. Thirty patients on stable warfarin anticoagulation (international normalized ratio [INR], 1.7-3.3) were randomized to receive 240 mL of CJ or 240 mL of placebo beverage, matched for color and taste, once daily for 2 weeks. The INR values and plasma levels of R- and S-warfarin were measured during the 2-week period and a 1-week follow-up period. The CJ and placebo groups (n=14 and 16, respectively) did not differ significantly in mean plasma R- and S-warfarin concentrations. Eight patients (4 on CJ, 4 on placebo) developed minimally elevated INR (range, 3.38-4.52) during the treatment period. Mean INR differed significantly (P<.02) only on treatment day 12; at all other time points, the groups did not differ. Cranberry juice has no effect on plasma S- or R-warfarin plasma levels, excluding a pharmacokinetic interaction. A small though statistically significant pharmacodynamic enhancement of INR by CJ at a single time point is unlikely to be clinically important and may be a random change. Enhanced warfarin anticoagulation attributed to CJ in anecdotal reports may represent a chance temporal association.

A Flavonoid Fraction from Cranberry Extract Inhibits Proliferation of Human Tumor Cell Lines

Posted: October 13, 2010
Authors: Ferguson PJ,Kurowska E, Freeman DJ, Chambers AF,
Journal: J Nutr 134:1529-1535

Abstract: In light of the continuing need for effective anticancer agents, and the association of fruit and vegetable consumption with reduced cancer risk, edible plants are increasingly being considered as sources of
anticancer drugs. Cranberry presscake (the material remaining after squeezing juice from the berries), when fed to mice bearing human breast tumor MDA-MB-435 cells, was shown previously to decrease the growth and
metastasis of tumors. Therefore, further studies were undertaken to isolate the components of cranberry that
contributed to this anticancer activity, and determine the mechanisms by which they inhibited proliferation. Using
standard chromatographic techniques, a warm-water extract of cranberry presscake was fractionated, and an
acidified methanol eluate (Fraction 6, or Fr6) containing flavonoids demonstrated antiproliferative activity. The
extract inhibited proliferation of 8 human tumor cell lines of multiple origins. The androgen-dependent prostate cell
line LNCaP was the most sensitive of those tested (10 mg/L Fr6 inhibited its growth by 50%), and the estrogen independent breast line MDA-MB-435 and the androgen-independent prostate line DU145 were the least sensitive
(250 mg/L Fr6 inhibited their growth by 50%). Other human tumor lines originating from breast (MCF-7), skin
(SK-MEL-5), colon (HT-29), lung (DMS114), and brain (U87) had intermediate sensitivity to Fr6. Using flow
cytometric analyses of DNA distribution (cell cycle) and annexin V-positivity (apoptosis), Fr6 was shown in
MDA-MB-435 cells to block cell cycle progression (P 0.05) and induce cells to undergo apoptosis (P 0.05) in
a dose-dependent manner. Fr6 is potentially a source of a novel anticancer agent.

Anti-microbial activity of urine after ingestion of cranberry: a pilot study

Posted: October 13, 2010
Authors: Lee YL,Najm WI, Owens J, Thrupp L, Baron S, Shanbrom E, Cesario T
Journal: eCAM 7(2):227–232

Abstract: We explore the anti-microbial activity of urine specimens after the ingestion of a commercial cranberry preparation. Twenty subjects without urinary infection, off antibiotics and all supplements or vitamins were recruited. The study was conducted in two phases: in phase 1, subjects collected the first morning urine prior to ingesting 900mg of cranberry and then at 2, 4 and 6 h. In phase 2, subjects collected urine on 2 consecutive days: on Day 1 no cranberry was ingested (control specimens), on Day 2, cranberry was ingested. The pH of all urine specimens
were adjusted to the same pH as that of the first morning urine specimen. Aliquots of each specimen were independently inoculated with Escherichia coli, Klebsiella pneumoniae or Candida albicans. After incubation, colony forming units/ml (CFU ml 1) in the control specimen
was compared with CFU ml 1 in specimens collected 2, 4 and 6 h later. Specimens showing 50% reduction in CFU ml 1 were considered as having ‘activity’ against the strains tested. In phase 1, 7/20 (35%) subjects had anti-microbial activity against E. coli, 13/20 (65%) against K. pneumoniae and 9/20 (45%) against C. albicans in specimens collected 2–6 h after ingestion of cranberry. In phase 2, 6/9 (67%) of the subjects had activity against K. pneumoniae. This pilot
study demonstrates weak anti-microbial activity in urine specimens after ingestion of a single dose of commercial cranberry. Anti-microbial activity was noted only against K. pneumoniae 2–6 h after ingestion of the cranberry preparation.

Cranberry cocktail juice, cranberry concentrates,

Posted: October 13, 2010
Authors: Lipson SM, Cohen P, Zhou J,Burdowski A
Journal: Mol Nutr Food Res 51:752-758

Abstract: Studies were performed to investigate the effect of several cranberry and grape juice extracts on the inhibition of reovirus infectivity following cell culture inoculation. Infectivity testing was performed utilizing cranberry juice extracts NutriCran-100TM and NutriCran-90TM. At 5% extract concentrations, titers were reduced by ca. 50%. Cranberry cocktail juice caused an infectivity loss of ca. 10%. We ascribe these data to higher concentrations of proanthocyanidins (PACs) in the cranberry extracts.
Further testing was performed utilizing purified high and low molecular weight cranberry PAC fractions (CB HMW and CB LMW, respectively), a cranberry flavonol glycoside (CB EToAc), cranberry anthocyanins (CB CA), and a grape PAC extract. Reovirus titers were reduced to undetectable levels at PAC concentrations f0.2%. CB CA had no effect on the inhibition of infectivity titers. Loss of infectivity titers was in the order: GP PACACB HMWACB LMWACB EToAc. Probe homogenization of CB HMWenhanced the extract to efficacy levels equal to that of grape PAC. Reovirus dsRNA segments were undetectable 96-h postcranberry cocktail juice pretreatment of MA-104 cell cultures. This study indicates an inhibition of reovirus infectivity titers by cranberry or grape juices or their purified PAC extracts. Viral inhibition probably occurs at the host cell surface.

Effects of Cranberry Juice on Pharmacokinetics of -Lactam

Posted: October 13, 2010
Authors: Li M, Andrew MA, Wang J, Salinger DH, Vicini P,
Journal: Antimicrob Agents Chemother 53(7):2725-32

Abstract: Cranberry juice consumption is often recommended along with low-dose oral antibiotics for prophylaxis for
recurrent urinary tract infection (UTI). Because multiple membrane transporters are involved in the intestinal
absorption and renal excretion of -lactam antibiotics, we evaluated the potential risk of pharmacokinetic
interactions between cranberry juice and the -lactams amoxicillin (amoxicilline) and cefaclor. The amoxicillin-
cranberry juice interaction was investigated in 18 healthy women who received on four separate occasions
a single oral test dose of amoxicillin at 500 mg and 2 g with or without cranberry juice cocktail (8 oz) according
to a crossover design. A parallel cefaclor-cranberry juice interaction study was also conducted in which 500 mg
cefaclor was administered with or without cranberry juice cocktail (12 oz). Data were analyzed by noncompartmental
methods and nonlinear mixed-effects compartmental modeling. We conclude that the concurrent
use of cranberry juice has no significant effect on the extent of oral absorption or the renal clearance of
amoxicillin and cefaclor. However, delays in the absorption of amoxicillin and cefaclor were observed. These
results suggest that the use of cranberry juice at usual quantities as prophylaxis for UTI is not likely to alter
the pharmacokinetics of these two oral antibiotics.

Cranberry components inhibit interleukin-6, interleukin-8, and prostaglandin E production by lipopolysaccharide-activated gingival fibroblasts

Posted: October 11, 2010
Authors: Bodet C, Chandad F, Grenier D
Journal: Eur J Oral Sci 115(1):64-70

Abstract: Periodontitis is a chronic inflammatory disease that affects the tooth supporting tissues. Gingival fibroblasts are the most abundant cells in periodontal tissues and participate actively in the host inflammatory response to periodontopathogens, which is known to mediate local tissue destruction in periodontitis. The aim of this study was to investigate the effect of a proanthocyanidin-enriched cranberry fraction, prepared from cranberry juice concentrate, on inflammatory mediator production by gingival fibroblasts stimulated by the lipopolysaccharide (LPS) of Aggregatibacter actinomycetemcomitans. Interleukin (IL)-6, IL-8, and prostaglandin E(2) (PGE(2)) production by fibroblasts treated with the cranberry fraction and stimulated by A. actinomycetemcomitans LPS was evaluated by enzyme-linked immunosorbent assay. Changes induced by A. actinomycetemcomitans LPS and the cranberry fraction in the expression and phosphorylation state of fibroblast intracellular signaling proteins were characterized by antibody microarrays. The LPS-induced IL-6, IL-8, and PGE(2) responses of gingival fibroblasts were inhibited by treatment with the cranberry fraction. This fraction was found to inhibit fibroblast intracellular signaling proteins, a phenomenon that may lead to a down-regulation of activating protein-1 activity. Cranberry components also reduced cyclooxygenase 2 expression. This study suggests that cranberry juice contains molecules with interesting properties for the development of new host-modulating therapeutic strategies in the adjunctive treatment of periodontitis.

Antimicrobial action of the American cranberry constituents; phenolics, anthocyanins, and organic acids, against Escherichia coli O157:H7.

Posted: January 22, 2010
Authors: Lacombe A, Wu VC, Tyler S, Edwards K
Journal: Int J Food Microbiol 139(2010):102-7

Abstract: We investigated the antimicrobial effect of constituents of the American cranberry (Vaccinium macrocarpon); sugar plus organic acids, phenolics, and anthocyanins, against Escherichia coli O157:H7. Each fractional component was assayed over a 24-h period with 5-log initial inocula to determine the minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), and log CFU/ml reductions, at their native pH and neutral pH. Each fraction produced significant reductions (P<0.05) at the native pH: MICs for sugars plus organic, phenolics, and anthocyanins were 5.6/2.6 Brix/acid (citric acid equivalents) 2.70g/L (gallic acid equivalent), and 14.80mg/L (cyanidin-3-glucoside equivalent), respectively. Sugars plus organic acids at native pH (3) produced a reduction below detectable limits (<1 log CFU/ml) compared to the control at 24h for 11.3/5.2 and 5.6/2.6 Brix/acid. Phenolics at native pH (4) produced reductions below detectable limits compared to the control at 24h and initial inocula for treatments of 5.40 and 2.70g/L. Anthocyanins at native pH (2) produced reductions below detectable limits for treatments of 29.15 and 14.80mg/L cyanidin-3-glucoside equivalents. Neutralized phenolics and anthocyanins had the same MIC and MBC as those at their native pH. Neutralized sugars plus organic acids did not inhibit bacterial growth compared to the control. Neutralized phenolics reduced bacteria below detectable limits in treatments of 5.40g/L and 2.70g/L compared to the control. Neutralized anthocyanins reduced bacterial growth below detectable limits at the concentration of 29.15mg/L, but at 14.80mg/L there was no significant reduction. Stationary-phase cells of E. coli O157:H7 were treated with 5% of each fraction in 0.8% NaCl for 20min and viewed under transmission electron microscopy. All fractions caused significant damage compared the control. Sugars plus organic acids caused visible osmotic stress, while phenolics and anthocyanins caused disintegration of the outer membrane.