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.

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.

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.

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.

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; P0.01), an effect that plateaued during the last phase of the study (500 ml CJC/d: +8.1+/-10.0% v. 0 ml CJC/d; P0.0001). Multivariate analyses revealed that changes in plasma apo A-I (R(2)=48%, P0.0001) and triacylglycerol (R(2)=16%, P0.005) 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.

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.

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.

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.

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.

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.