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Polyphenols Anggur Mengurangkan Tekanan Darah dan Meningkatkan Aliran-Mediated Vasodilatasi Pada Pesakit Lelaki Yang Mengidap Metabolic Syndrome

Polyphenols Anggur Mengurangkan Tekanan Darah dan Meningkatkan Aliran-Mediated Vasodilatasi Pada Pesakit Lelaki Yang Mengidap Metabolic Syndrome

Sepasukan penyelidik seramai 5 orang telah menjalankan kajian keatas ekstrak anggur bagi melihat kemampuan polyphenol anggur mampu mengurangkan tekanan darah disamping meningkat aliran mediated vasodilatai ke atas pesakit lelaki yang mengidap sindrom metabolik.

Penyelidik tersebut terdiri daripada Jacqueline Barona, Juan C. Aristizabal, Christopher N. Blesso2, Jeff S. Volek, and Maria Luz Fernandez daripada Department of Nutritional Sciences, and Department of Kinesiology, University of Connecticut, Storrs, CT; dan School of Microbiology, University of Antioquia, Medellin, Colombia.

Hasil kajian itu mendapati polyphenol yang terdapat dalam ekstrak anggur berupaya mengurangkan tekanan darah serta mempertingkatkan fungsi jantung.


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Kredit: http://jn.nutrition.org

Grape Polyphenols Reduce Blood Pressure and Increase Flow-Mediated Vasodilation in Men with Metabolic Syndrome1

  1. Jacqueline Barona2,4,
  2. Juan C. Aristizabal2,3,
  3. Christopher N. Blesso2,
  4. Jeff S. Volek2,3, and
  5. Maria Luz Fernandez2,*

Author Affiliations

  1. 2Department of Nutritional Sciences, and
  2. 3Department of Kinesiology, University of Connecticut, Storrs, CT; and
  3. 4School of Microbiology, University of Antioquia, Medellin, Colombia


We evaluated the effects of grape polyphenols in individuals classified with metabolic syndrome (MetS). Men (n = 24) aged 30–70 y were randomly assigned to consume either a freeze-dried grape polyphenol powder (GRAPE) or a placebo for 30 d in a double-blind, crossover design, separated by a 3-wk washout period. Participants were asked to maintain their usual diet and physical activity during the study and abstain from consuming polyphenol-rich foods. MetS criteria including blood pressure (BP) and markers of vascular endothelial function including brachial artery flow-mediated vasodilation (FMD), plasma total nitrite + nitrate (NOx) to estimate NO production, plasma soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured at the end of each dietary period. Systolic BP (P < 0.0025) and plasma sICAM-1 concentrations (P < 0.025) were lower, whereas the FMD response was higher (P < 0.0001), during the GRAPE compared with the placebo period. In addition, changes in sVCAM-1 concentrations between periods were positively correlated with changes in systolic BP (r = 0.45; P < 0.05). Although NOx concentrations did not differ between periods, changes in systolic BP were negatively correlated with changes in NOx concentrations (r = −0.44; P < 0.05), indicating the vasodilating properties of NO. Other MetS variables did not differ between the GRAPE and placebo periods. These results suggest that GRAPE polyphenols may potentiate vasorelaxation and reduce BP and circulating cell adhesion molecules, resulting in improvements in vascular function.


Metabolic syndrome (MetS)5 is a cluster of risk factors for type 2 diabetes and cardiovascular disease (CVD) (1), including high blood pressure (BP), dyslipidemia [high TG, low HDL cholesterol (HDL-C)], raised fasting glucose, and central obesity. Having 3 of 5 of these characteristics qualifies a person as having MetS (1). Overconsumption of carbohydrate relative to a person’s level of insulin resistance is a driving force behind MetS (2, 3). Obesity and overweight are also associated with development of MetS (4, 5). Approximately two-thirds of adults aged ≥20 y (70.8% men vs. 61.8% women) are classified as overweight or obese in the US (6). The growing number of individuals with excess adipose tissue may also be a result of individuals consuming carbohydrate at levels that exceed their ability to directly oxidize them, thereby contributing to the high prevalence of MetS (34.2% among all U.S. adults ≥20 y). Thus, MetS has become one of the major public health and clinical problems in the US and worldwide (1, 7).

MetS is associated with endothelial dysfunction (8), which is one of the first clinically detectable alterations in atherosclerosis development (9), and its presence is predictive of CVD (10, 11). Endothelial dysfunction is characterized by an imbalance in the release of vasoactive substances such as endothelium-derived NO (12), which is considered to be an important regulator of vascular function due to its vasodilator properties, and its inhibition on platelet aggregation and adhesion, leukocyte-endothelial interactions, and expression of adhesion molecules by endothelial cells (10, 13).

Flow-mediated vasodilation (FMD) of the brachial artery is a noninvasive ultrasound method to assess endothelial function (12, 14), which has been proposed to represent a functional bioassay for endothelium-derived NO availability in humans (15). Thus, reduced FMD has been described in the presence of CVD risk factors and related diseases (14).

Treatment with antioxidants improves FMD in individuals with hypercholesterolemia, diabetes, and CVD (10, 16). Polyphenols, which are widely distributed among fruits and vegetables, have demonstrated a wide range of biological activities, including antioxidant, antiinflammatory, and hypolipidemic effects (17). These activities can potentially ameliorate MetS biomarkers and decrease the risk of CVD. Additionally, studies in experimental models of CVD have shown that polyphenol-rich sources enhance endothelial vasoprotective mechanisms by inducing the formation of NO and reducing oxidative stress in the arterial wall (16). Grapes contain numerous polyphenols such as flavans, anthocyanins, flavonols, and stilbenes (resveratrol), which have been shown to modulate LDL oxidation, oxidative stress, dyslipidemia, and inflammation (1721). Most of these studies have been done in cells and animal models. However, there are fewer studies addressing the beneficial effects of grape polyphenols on biomarkers of MetS (22) and on FMD in adult patients with this disorder (23, 24).

Therefore, we aimed to evaluate the effects of the consumption of a grape preparation [grape polyphenol powder (GRAPE)] of standardized polyphenol content on vascular endothelial function, inflammatory markers, and clinical parameters in men classified with MetS, a high-risk population for CVD and type 2 diabetes. We hypothesized that the GRAPE polyphenols would positively modify MetS characteristics and improve vascular function.

Participants and Methods

Experimental design.

Twenty-five men (30–70 y) classified with MetS according to the revised American Heart Association-National Cholesterol Education Program (AHA-NCEP)-ATPIII definition (25) (having 3 of the 5 following characteristics: waist circumference (WC) >102 cm, BP ≥130/85; plasma TG ≥1.7 mmol/L; HDL-C <1.0 mmol/L, and fasting plasma glucose ≥5.5 mmol/L) were recruited. The sample size estimation was based on preliminary data from our laboratory following a similar protocol as this study (22). The exclusion criteria were renal disease, diabetes, heart disease, TG >5.7 mmol/L, fasting plasma glucose >7 mmol/L, or use of antiinflammatory drugs. This study was approved by the University of Connecticut-Storrs Institutional Review Board and all participants signed the written, informed consent.

Participants (n = 25) were randomized and double-blind allocated to the GRAPE supplement or to a placebo in a crossover experimental design. The placebo was designed to match the grape powder in terms of look, feel, taste, and macronutrients but without any polyphenols. The polyphenol content and the nutrient composition of the supplement are presented in Table 1. Following 30 d of consuming the GRAPE or placebo supplements, participants underwent a 3-wk washout period and were allocated to the alternate treatment for an additional 30 d. Participants consumed 46 g/d of GRAPE powder, which was reconstituted immediately prior to consumption and corresponded to an equivalent of 2 servings/d of grapes. Participants were asked to abstain from consuming polyphenol-rich foods, including tea, berries, grapes, and wine, during the whole study. To monitor compliance, participants completed a short questionnaire every week. When compliance was <70%, participants were asked to leave the study. Additionally, participants completed a 5-d dietary record (including 2 weekend days) and a 7-d physical activity diary at the baseline and end of each period to ensure no changes in diet or exercise. Twenty-four individuals completed the study and only one person withdrew due to personal reasons.

View this table:


Phytochemical concentration and nutrient analysis of the freeze-dried grape preparation

Anthropometrics: weight, height, and BMI.

Body weight was measured to the nearest 0.1 kg on a calibrated digital scale. Height was measured to the nearest 0.1 cm at screening/baseline using a portable stadiometer. BMI was calculated by dividing weight in kg by height in squared meters (m2).


WC was measured at the end of a normal expiration at the superior border of the iliac crest to the nearest 0.1 cm using a nonflexible body measuring tape over the skin, at baseline, at the end of each period (wk 4 and 11), and after the washout period.

Dietary and physical activity analysis.

The Nutrient Database Systems for Research version 8.0 (Nutrition Coordinating Center, University of Minnesota) was used for nutrient analysis. Physical activity obtained from the exercise diaries was expressed as the amount of time in hours per week.


BP (systolic and phase-V diastolic) was measured on the left arm at the heart level after at least 5 min of resting in sitting position and using an automated BP monitor (Omron, Healthcare). Two recordings, separated by at least 1 min were made and the mean value was used. If there was more than a 5-mm Hg difference between the first and second readings, additional readings were obtained and then the mean value of these multiple readings was used (26).

Measurement of endothelial-dependent FMD.

Brachial artery FMD was measured by high-frequency, ultrasonographic imaging at the end of each dietary period (GRAPE and placebo), respectively. An ultrasound system (T3000; Terason) equipped with vascular software for 2-dimensional imaging, color, and spectral Doppler, an internal electrocardiogram monitor, and a 5- to 12-MHz multi-frequency linear array transducer was used to simultaneously assess brachial artery diameter and blood flow velocity changes. Timing of each image frame with respect to the cardiac cycle was determined with a simultaneous electrocardiogram recording on the ultrasound system video monitor.

Participants were instructed to arrive in the morning (at the same time for both periods) after having fasted for 12 h and abstained from caffeine for 12 h; tobacco products, alcohol, exercise, and aspirin/over-the-counter medications for 24 h, and vitamin/supplements for 72 h (15). All measurements were performed in a quiet, darkened, and temperature-controlled room after a 15-min resting period of the participant lying in a supine position. The right arm was extended and positioned at an angle of ∼60° from the torso at the level of the heart. A rapid inflation and deflation pneumatic cuff was placed on the arm just below the medial epicondyle of the humerus to create a flow-stimulus with occlusion. The brachial artery was imaged in the distal third of the upper arm with the transducer placed to image the brachial artery in a longitudinal axis with clear visualization of the anterior and posterior vessel walls; the blood velocity was simultaneously collected with an insonation angle of 60°. After optimization of the image and blood velocity signal, resting end-diastolic baseline brachial artery diameter and blood flow were recorded for 1 min. Subsequently, arterial occlusion was created using a rapid cuff inflator to suprasystolic pressure (∼200 mm Hg) during 5 min. Afterward, the cuff was deflated, which induces a brief high-flow state through the brachial artery (reactive hyperemia) to accommodate the downstream dilated resistance vessels. The resulting increase in shear stress causes the brachial artery to dilate. Brachial artery diameter and blood flow velocity were simultaneously and continuously recorded for 4 min (1 min before and 3 min after cuff deflation). The anatomical characteristics and image landmarks were taken into account to help with the placement of the transducer in the same location on the arm for the second visit. All vascular measurements and analysis were performed by the same person who was unaware of the treatment groups.

FMD data analysis.

Ultrasound images were recorded at a rate of 5 frames/s using screen capture software (Camtasia Studio, TechSmith) and converted into an AVI file. Off-line analyses of diameters and velocities were performed using automated edge-detection software with end-diastolic gating (Brachial Analyzer 4.0, Medical Imaging Applications). Resting diameters were calculated as the average of images taken over the 1-min baseline. Postocclusion (3-frame smoothing average) changes in arterial diameter, as a consequence of reactive hyperemia, were determined. The peak postocclusion diameter was determined as the highest 3-frame average. Brachial artery FMD was compared with the baseline diameter and expressed as the relative (%) and absolute (millimeters) change from this baseline diameter (15, 27).

From end-diastolic synchronized diameter (D; mm) and velocity data (V; m ⋅ s−1), shear rate (an estimate of shear stress without viscosity; s−1) was calculated as 4 times mean blood velocity per vessel diameter: 4 ⋅ (V ⋅ 1000) ⋅ D−1 (28). The shear rate postocclusion AUC, calculated for data up to the point of maximal postocclusion diameter (FMD) (29), was determined to quantify the cumulative exposure to shear experienced by the artery, which is considered to be the major stimulus for the peak FMD response (15).

Blood collection.

After 12-h overnight fasting, blood was drawn from an antecubital vein using EDTA-coated collection tubes. Blood was immediately centrifuged at 2200 × g for 20 min at 4°C to obtain plasma. Preservatives (1 mL/L sodium azide, 1 mL/L phenylmethylsulphonyl fluoride, and 5 mL/L aprotinin) were added. Plasma was divided into aliquots and frozen at −80°C for further analysis.

Plasma lipids.

The average of 2 blood draws in the same week was used to determine plasma total cholesterol (30), LDL cholesterol, HDL-C, and TG at baseline, the end of each dietary period, and after the washout period. An automatic analyzer was used to simultaneously determine all parameters (Cobas 111, Roche Diagnostics) using enzymatic methods.

Plasma NO.

The total plasma nitrite + nitrate (NOx) concentration was measured as an estimate of total NO production in vivo by using a spectrophotometric method (Cayman Chemical). Preservative-free plasma samples were ultrafiltered through a 30-kDa molecular weight cutoff filter (Amicon) using a microcentrifuge for 30 min to reduce background absorbance. The intra-assay percent CV was 1.6%. Plasma preservation cocktail interferes with this method; therefore, we could only measure it in 17 of the participants.

Inflammatory markers.

Soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured in duplicate in the same assay using the Human CVD Panel 1 MILLIPLEX MAP kit (Millipore) following the manufacturer’s instructions. Plasma samples were diluted 1:100 and simultaneously quantified using Luminex xMAP technology. All assays were conducted in the same day to decrease variability (intra-assay percent CV was 6% for sICAM-1 and 5% for sVCAM-1).

Statistical analysis.

A paired samples t test was conducted to analyze differences between the GRAPE and placebo periods using SPSS version 17 for Windows. Differences with a P ≤ 0.05 were considered significant. Data are presented as means ± SD. Pearson correlation coefficient analysis was used to evaluate associations between the measured variables.


MetS criteria and participant characteristics

Participants (51.3 ± 9.6 y old) had a lower resting systolic BP after the GRAPE period (122 ± 11 mm Hg) compared with the placebo period (128 ± 10 mm Hg) (P < 0.0025). Other criteria for MetS did not differ between periods (Table 2). Nevertheless, the percentage of participants who met the WC criterion for MetS (>102 cm) was higher during the placebo period (71%) compared with 54% during the GRAPE period. We also measured all criteria for MetS both at baseline and after the 3-wk washout. BP, WC, plasma lipids, and plasma glucose did not differ between these 2 time periods (P < 0.05). Thus, all participants started the corresponding treatment with the same MetS characteristics.

View this table:


Characteristics of MetS in men after 30-d placebo and GRAPE periods1

Diet and physical activity

The compliance of our participants regarding supplement consumption and abstention of polyphenol-rich food was >90%. There were no differences in the participants’ energy or macronutrient intake during GRAPE or placebo consumption (Table 3). Participants’ physical activity did not differ between the placebo (3.74 ± 2.8 h/wk) and GRAPE (3.74 ± 2.6 h/wk) periods.

View this table:


Energy, fat, carbohydrate, and protein intakes in men with MetS during 30-d placebo and GRAPE periods1

Vascular endothelial function markers


Brachial artery baseline diameters during the placebo (4.9 ± 0.51 mm) and GRAPE (4.8 ± 0.46 mm) periods differed (P < 0.05). Peak FMD was higher after GRAPE consumption (5.7 ± 2.96%; 0.28 ± 0.15 mm) compared with the placebo (4.0 ± 2.4%; 0.20 ± 0.12 mm) (P < 0.001) (Fig. 1A). The mean shear rate postocclusion AUC did not differ between the GRAPE (829 ± 268) and placebo (717 ± 197) periods.


Percent change in FMD responses in men with MetS after 30-d placebo and GRAPE periods. Values are mean ± SD, n = 24. *Different from placebo, P < 0.001. FMD, flow-mediated vasodilation; GRAPE, grape polyphenol powder; MetS, metabolic syndrome.

Plasma NOx.

The NOx concentration was not different after the GRAPE (38.3 ± 25.3 μmol/L) and placebo (36.9 ± 21.6 μmol/L) periods (n = 17). However, after GRAPE consumption, the mean plasma NO metabolites concentration was 3.7% higher than after the placebo.

Inflammatory markers

The plasma sICAM-1 concentration was lower after consumption of GRAPE (142 ± 50 μg/L) compared with placebo (151 ± 51 μg/L) (P < 0.025) (Fig. 2). The plasma sVCAM-1 levels did not differ between the GRAPE (1020 ± 285 μg/L) and placebo (1020 ± 240 μg/L).


Plasma sICAM-1 concentrations in men with MetS after 30-d placebo and GRAPE periods. Values are mean ± SD, n = 24. *Different from placebo, P < 0.025. GRAPE, grape polyphenol powder; MetS, metabolic syndrome; sICAM-1, soluble intracellular adhesion molecule 1.

Correlations between vascular and inflammatory markers

Changes in sVCAM-1 were positively correlated with changes in systolic BP (r = 0.45; P < 0.05) (Fig. 3A). Although the NOx concentrations did not differ between periods, changes in systolic BP were negatively correlated with changes in NOx concentrations (r = −0.44; P < 0.05), indicating the vasodilating properties of NO (Fig. 3B).


Correlations between changes in sVCAM-1 concentrations and systolic BP (A) and changes in plasma NOx concentrations and systolic BP (B) after the placebo and GRAPE periods in men with MetS. P ≤ 0.05 is considered significant. BP, blood pressure; GRAPE, grape polyphenol powder; MetS, metabolic syndrome; NOx, total nitrites + nitrates; sVCAM-1, soluble vascular adhesion molecule 1.


Due to the multifactorial nature of MetS, there are no approved drugs that can consistently reduce all of the components of MetS over the long term (31). Therefore, there is a growing interest in therapeutic strategies that might target multiple risk factors more effectively, thereby minimizing problems with polypharmacy (32). Researchers have emphasized that the treatment for MetS must be focused on lifestyle changes (31). Among the lifestyle factors that can have the most dramatic effect on MetS, carbohydrate restriction is most effective (2, 3335). In addition to carbohydrate restriction, including foods rich in bioactive nutrients may also have a role in improving the features of MetS. This study, to the best of our knowledge, is the first to evaluate the effects of a grape preparation of standardized polyphenol content on MetS parameters and on vascular endothelial function in free-living men aged 30–70 y.

We demonstrated that, compared with placebo, the daily consumption of GRAPE for 30 d significantly improved vascular endothelial function and biomarkers of MetS by increasing FMD response, lowering systolic BP, and decreasing circulating inflammatory molecules. As expected, the participants maintained their usual body weight, diet, and physical activity throughout the whole study. Thus, the beneficial effects observed during the GRAPE period cannot be attribute to weight loss, decreased energy intake, or modifications of the macronutrient composition of the diets.

It is not known whether improving endothelial function in people with MetS will reduce their risk for type 2 diabetes and vascular events in the future (36). A study with 819 participants having both MetS and endothelial dysfunction (measured by FMD) showed they were at higher risk for CV events than those with either one in isolation (37). The authors concluded that the combined use of MetS diagnosis criteria and FMD technique identifies those who are at higher risk of CV events. The US National High Blood Pressure Education program estimates that a 5-mm Hg reduction of systolic BP in the population would result in a 14% overall reduction in mortality due to stroke, a 9% reduction in mortality due to CVD, and a 7% decrease in all-cause mortality (38). We demonstrated that on average, compared with placebo, men with MetS consuming grape polyphenols for only 30 d decreased their systolic BP by 6 mm Hg. Furthermore, they significantly improved their FMD response. These results suggest that the GRAPE product and dose (∼250 g fresh grapes/d) used in this study may be beneficial for men with MetS by potentially decreasing their risk for CV events in the long term.

Although some studies have not found beneficial effects of grape polyphenols on markers of vascular function, such as BP and FMD in humans (3941), numerous publications have described the positive effects of grape products in different populations [reviewed in (16, 42, 43)]. However, there are few studies evaluating the effects of grape polyphenols on people with MetS. Sivaprakasapillai et al. (44) randomized participants with MetS into 3 parallel groups to consume placebo, 150 mg grape seed extract/d, or 300 mg grape seed extract/d for a 4-wk treatment period. Both systolic and diastolic BP decreased after treatment with the grape seed extracts compared with placebo (44). Similar to our findings, they did not find any significant changes in serum lipids or glucose (44).

Another study evaluated the vascular endothelial effects of a standardized grape product similar to ours in healthy, normal, young men (45). They found that both the acute intake (within 3 h) and the consumption twice daily for 3 wk of the grape product (equivalent to ∼156 g fresh grapes) significantly improved FMD compared with control (sugar solution) (45). No acute changes in BP or lipid profiles were observed (45). In our study, we used a slightly greater dose (equivalent to ∼250 g fresh grapes) compared with the above study. However, we evaluated a more challenging population with established CVD risk factors and with increased levels of oxidative stress that may inactivate NO at the endothelium. Thus, the beneficial effects observed on endothelial function in our study may indicate an increased NO bioavailability after GRAPE consumption.

To assess the effects of GRAPE consumption on vasodilation, we measured NO status by evaluating plasma NOx, the stable and final metabolites of NO (10). We found no differences in plasma NOx between the placebo and GRAPE periods. This may be due to the lack of statistical power, because we could analyze only a subset of the samples (n = 17). In addition, this test is not specific for endothelial NO production and could reflect other sources of NO [e.g., n NO synthase (NOS) and iNOS and/or exogenous sources such as food and gastrointestinal microorganisms] (46). Nevertheless, we showed that after GRAPE polyphenol consumption, participants experienced protective vascular effects consistent with the vasorelaxing actions of endothelial-derived NO, as described before. Moreover, we found a negative association between the changes in systolic BP and changes in NOx concentrations (r = −0.44; P < 0.05), suggesting the vasorelaxing effect of increased bioavailability of NO. There is limited information of grape-supplemented studies measuring plasma NO metabolites in participants with MetS; however, 2 studies with different populations found diverse results (47, 48). Healthy volunteers consuming 7 mL/(kg ⋅ d) of purple grape juice during 14 d increased their platelet-derived NO production (47). Conversely, smokers consuming 200 mg/d of monomeric and oligomeric flavanols from grape seeds did not change their plasma concentrations of NO surrogates after 8 wk of supplementation compared with baseline (48). These findings suggest that the dose and type of grape product, time of supplementation, and the population studied are important factors when analyzing the specific effects of grapes on endothelial function markers (43).

An association between endothelial dysfunction and hypertension is well known (49). It has been suggested that hypertension-associated vascular endothelial dysfunction is related to local and systemic inflammation (49). In accordance with this, we found moderate positive correlations between changes in sVCAM-1 concentrations and changes in systolic BP (r = 0.45; P < 0.05), suggesting that the decrease in circulating inflammatory molecules may reflect a less dysfunctional endothelium, capable of producing NO, which further induces vasorelaxing responses decreasing BP. Several mechanisms, mostly from in vitro studies, have been described to explain these protective effects of grape polyphenols on the endothelium (16, 50). It is proposed that besides their antioxidant activity at the endothelium, polyphenols increase the activity (via phosphorylation status) and expression of the endothelial NOS, inducing NO production (16, 45).

Although there could be concern regarding consumption of supplements, the compliance of our participants was >90% and there was no withdrawal due to poor compliance. It is possible that the bioavailability of the polyphenols present in GRAPE may have prevented us from finding any significant effects on blood lipids. The bioavailability of polyphenols differs greatly depending on their chemical structure and food matrix, among other factors (51, 52). It has been indicated that some cells, such as endothelial cells, may readily incorporate polyphenols by specific mechanisms (52). Thus, the plasma concentration of polyphenols may not have been sufficient to affect lipid values. However, we did not measure polyphenol metabolites in the plasma of the participants to provide evidence of absorption or bioavailability.

Among the strengths of this study are its crossover design, which reduces the influence of confounding covariates, because each patient served as his own control. Moreover, the grape preparation used in this study was a freeze-dried, dehydrated preparation of red, green, and blue-black California seeded and seedless grapes; this type of preparation retains virtually all of the active ingredients in fresh grapes and has been used in a previous study showing vasoprotective endothelial effects in healthy participants (45). Furthermore, because we used a placebo designed to match the grape powder in terms of look, feel, taste, and macronutrients, except for the polyphenols, we can be more certain that the beneficial effects observed with GRAPE are likely due to its polyphenol content.

In summary, the results of this study suggest that in men (30–70 y) with MetS, the chronic consumption of a grape preparation (GRAPE) of standardized polyphenol content improves vascular endothelial dysfunction consistent with increased NO bioavailability. This study further supports the consumption of polyphenol-rich products derived from grapes as an approach to reduce future risk of CVD, especially in those with MetS.


J.B. conducted the research, analyzed data, and wrote the paper; J.A. collected anthropometric data, helped with some experiments, and provided input for the paper; C.B. collected anthropometric data and provided input; J.V. participated in data analysis and interpretation; and M.L.F. designed research, analyzed data, and had primary responsibility for final content. All authors read and approved the final manuscript.


  • 1 Author disclosures: J. Barona, J. C. Aristizabal, C. N. Blesso, J. S. Volek, no conflicts of interest. M. L. Fernandez received an award from the California Table Grape Commission.

  • 5 Abbreviations used: BP, blood pressure; CVD, cardiovascular disease; FMD, flow-mediated vasodilation; GRAPE, grape polyphenol powder; HDL-C, HDL cholesterol; sICAM-1, soluble intercellular adhesion molecule-1; MetS, metabolic syndrome; NOS, NO synthase; NOx, total nitrites/nitrates; sVCAM-1, soluble vascular cell adhesion molecule-1; WC, waist circumference.

  • Manuscript received: April 9, 2012.
  • Initial review completed: May 9, 2012.
  • Revision accepted: June 4, 2012.

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