Cranberries (Vaccinium macrocarpon) are a rich source of phenolic phytochemicals, which likely contribute to their putative health benefits. A single-dose pharmacokinetic trial was conducted in 10 healthy adults 50y to evaluate the acute (24-h) absorption and excretion of flavonoids, phenolic acids and proanthocyanidins (PACs) from a low-calorie cranberry juice cocktail (54% juice). Inter-individual variability was observed in the Cmax and Tmax of many of these compounds in both plasma and urine. The sum total concentration of phenolics detected in plasma reached a peak of 34.2mug/ml between 8 and 10h, while in urine this peak was 269.8mug/mg creatinine, and appeared 2-4h earlier. The presence of PAC-A2 dimers in human urine has not previously been reported. After cranberry juice consumption, plasma total antioxidant capacity assessed using ORAC and TAP assays correlated with individual metabolites. Our results show phenolic compounds in cranberry juice are bioavailable and exert antioxidant actions in healthy older adults.

Abstract: We examined how intake of polyphenols modifies brachial artery flow-mediated dilation (FMD) at rest, and cycling anaerobic performance, in elite athletes. In the first randomized cross-over study, FMD was measured over a three-hour period on two occasions in eight elite male and female athletes after acute consumption of either polyphenols from cranberries and grape seeds (600 mg) or a polyphenol-free placebo drink. Consumption of the polyphenol-rich drink led to a significant increase in FMD compared to placebo (p = 0.02), with a peak at 60 min. In a second study, 12 elite male and female athletes completed a three-kilometer time trial (TT) on an ergocycle on two occasions in random order, either after consumption of 800 mg of polyphenols or a placebo. Acute intake of the polyphenol extract had no impact on the three-kilometer time trial completion. However, plasma lactate levels were significantly lower before and after the TT when subjects consumed the polyphenols vs. placebo (p 0.05). Results suggest that polyphenols from cranberries and grape seeds acutely modifies FMD at rest in elite athletes but this does not translate into enhanced cycling anaerobic performance.

The stiffening of arteries is a key step in atherogenesis leading to cardiovascular disease. It has been suggested that dietary polyphenols may be cardioprotective through possible favorable effects on oxidative stress and vascular function. The present study was undertaken in order to examine the effect of consuming low-calorie cranberry juice cocktail (CJC), a source of polyphenols, on arterial stiffness in abdominally obese men. We hypothesize that regular CJC consumption will reduce circulating oxidized low-density lipoproteins concentrations and have a beneficial impact on endothelial function. Thirty-five men (mean age +/- SD: 45 +/- 10 years) were randomly assigned to drink 500 mL CJC/day (27% juice) or 500 mL placebo juice (PJ)/day for 4 weeks in a double-blind crossover design. Augmentation index (AIx), an index of arterial stiffness, was measured by applanation tonometry of the radial artery and the cardiometabolic profile was assessed in each participant before and after each phase of the study. We found no significant difference in AIx changes between men who consumed CJC or PJ for 4 weeks (P = .5820). Furthermore, there was no between-treatment difference in changes in AIx responses to salbutamol (P = .6303) and glyceryl trinitrate (P = .4224). No significant difference was noted in other cardiometabolic variables between men consuming PJ or CJC. However, a significant within group decrease in AIx (mean decrease +/- SE; -14.0 +/- 5.8%, P = .019) was noted following the consumption of 500 mL CJC/day for 4 weeks. Our results indicate that the effect of chronic consumption of CJC on AIx was not significantly different from changes associated with the consumption of PJ. However, the significant within-group decrease in AIx following CJC consumption in abdominally obese men may deserve further investigation.

Purpose Cranberry juice (CJ) contains a remarkably high
concentration of polyphenols, considered to be beneficial for cardiovascular and bone health. The current double-blind, randomized study was designed to test whether daily consumption of double-strength Ocean Spray light CJ (2 9 230 ml) over 4 months has beneficial effects on vascular
function and on endothelial progenitor cells (EPCs) carrying the osteoblastic marker osteocalcin in particular.
Methods Atotal of 84 participants (49.5 ± 16.2 years)with
peripheral endothelial dysfunction and cardiovascular risk
factors were enrolled in this double-blind, randomized, controlled trial (69 completed the 4-month protocol—32 in the CJ group and 37 in the placebo group, respectively). Vascular responses to reactive hyperemia were measured non-invasively by peripheral arterial tonometry (EndoPAT). Peripheral blood mononuclear cells were stained for EPC markers, as well as osteocalcin, and counted by flow cytometry. Results Baseline characteristics were similar in bothgroups. The effect of CJ on peripheral endothelial function
and on circulating EPC counts (CD34?/CD133?/KDR?)
did not change during the study. A high percentage of
EPCs expressed osteocalcin (59.4 ± 35.7%). CJ, as compared
to placebo, induced a decrease in the fraction of
EPCs expressing osteocalcin (-8.64 ± 48.98 and
19.13 ± 46.11%, respectively, p = 0.019). Systemic levels
of the adhesion marker ICAM correlated significantly with
the number of EPCs expressing osteocalcin.
Conclusions The study demonstrated that long-term
supplementation of polyphenol-rich CJ did not improve
peripheral endothelial function. However, the decrease in
the fraction of osteocalcin? EPCs suggests a potential
beneficial effect of polyphenol-rich CJ.

Cranberries, high in polyphenols, have been associated with several cardiovascular health benefits, although limited clinical trials have been reported to validate these findings. We tested the hypothesis that commercially available low-energy cranberry juice (Ocean Spray Cranberries, Inc, Lakeville-Middleboro, Mass) will decrease surrogate risk factors of cardiovascular disease, such as lipid oxidation, inflammation, and dyslipidemia, in subjects with metabolic syndrome. In a randomized, double-blind, placebo-controlled trial, participants identified with metabolic syndrome (n = 15-16/group) were assigned to 1 of 2 groups: cranberry juice (480 mL/day) or placebo (480 mL/day) for 8 weeks. Anthropometrics, blood pressure measurements, dietary analyses, and fasting blood draws were conducted at screen and 8 weeks of the study. Cranberry juice significantly increased plasma antioxidant capacity (1.5 +/- 0.6 to 2.2 +/- 0.4 mumol/L [means +/- SD], P .05) and decreased oxidized low-density lipoprotein and malondialdehyde (120.4 +/- 31.0 to 80.4 +/- 34.6 U/L and 3.4 +/- 1.1 to 1.7 +/- 0.7 mumol/L, respectively [means +/- SD], P .05) at 8 weeks vs placebo. However, cranberry juice consumption caused no significant improvements in blood pressure, glucose and lipid profiles, C-reactive protein, and interleukin-6. No changes in these parameters were noted in the placebo group. In conclusion, low-energy cranberry juice (2 cups/day) significantly reduces lipid oxidation and increases plasma antioxidant capacity in women with metabolic syndrome. Copyright Copyright 2011 Elsevier Inc. All rights reserved.

BACKGROUND: Cranberry juice contains polyphenolic compounds that could improve endothelial function and reduce cardiovascular disease risk.
OBJECTIVE: The objective was to examine the effects of cranberry juice on vascular function in subjects with coronary artery disease.
DESIGN: We completed an acute pilot study with no placebo (n = 15) and a chronic placebo-controlled crossover study (n = 44) that examined the effects of cranberry juice on vascular function in subjects with coronary artery disease.
RESULTS: In the chronic crossover study, subjects with coronary heart disease consumed a research preparation of double-strength cranberry juice (54% juice, 835 mg total polyphenols, and 94 mg anthocyanins) or a matched placebo beverage (480 mL/d) for 4 wk each with a 2-wk rest period between beverages. Beverage order was randomly assigned, and participants refrained from consuming other flavonoid-containing beverages during the study. Vascular function was measured before and after each beverage, with follow-up testing >=12 h after consumption of the last beverage. Mean (+/-SD) carotid-femoral pulse wave velocity, a measure of central aortic stiffness, decreased after cranberry juice (8.3 +/- 2.3 to 7.8 +/- 2.2 m/s) in contrast with an increase after placebo (8.0 +/- 2.0 to 8.4 +/- 2.8 m/s) (P = 0.003). Brachial artery flow-mediated dilation, digital pulse amplitude tonometry, blood pressure, and carotid-radial pulse wave velocity did not change. In the uncontrolled pilot study, we observed improved brachial artery flow-mediated dilation (7.7 +/- 2.9% to 8.7 +/- 3.1%, P = 0.01) and digital pulse amplitude tonometry ratio (0.10 +/- 0.12 to 0.23 +/- 0.16, P = 0.001) 4 h after consumption of a single 480-mL portion of cranberry juice.
CONCLUSIONS: Chronic cranberry juice consumption reduced carotid femoral pulse wave velocity-a clinically relevant measure of arterial stiffness. The uncontrolled pilot study suggested an acute benefit; however, no chronic effect on measures of endothelial vasodilator function was found. This trial was registered at clinicaltrials.gov as NCT00553904.

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.

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.

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.

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.