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Grape extract

September 2007

Cardiovascular protective effects of resveratrol.

Resveratrol (3,4’,5-trihydroxy-trans-stilbene), a phytoalexin found in grape skins, peanuts, and red wine, has been reported to have a wide range of biological and pharmacological properties. It has been speculated that at low doses (such as consumed in the common diet) resveratrol may have cardioprotective activity. In this article we describe recent in vitro and in vivo studies in animal models. The results of these studies suggest that resveratrol modulates vascular cell function, inhibits LDL oxidation, suppresses platelet aggregation and reduces myocardial damage during ischemia-reperfusion. Although the reported biological data indicate that resveratrol is a highly promising cardiovascular protective agent, more studies are needed to establish its bioavailability and in vivo cardioprotective effects, particularly in humans.

Cardiovasc Drug Rev. 2004 Fall;22(3):169-88

Wine ingestion has no effect on lipid peroxidation products.

OBJECTIVE: Moderate alcohol consumption has been associated with beneficial effects on coronary heart disease. This positive effect has been partly attributed to the flavonol contents which promote vasodilatory, anti-aggregatory and antioxidative effects and protect low-density lipoprotein (LDL) cholesterol from oxidation. Thus, the present study was carried out to determine the acute effects of different wines on LDL oxidization in healthy volunteers. METHODS: Healthy male and female subjects (15/group) on a flavonol-restricted diet were randomly assigned to drink 300 ml wine from one of four different grapes and fermentation processes. Conjugated fatty acid dienes and thiobarbituric acid reactive substances (TBARS) were determined as a measure of LDL oxidation in serum at baseline and up to 96 h after wine ingestion. RESULTS: At baseline, mean conjugated dienes in serum were 12.5+/-6.2 micromol/l and mean TBARS in serum were 15.7+/-8.1 micromol/l. There were no differences between the groups and no effect of any wine type on conjugated dienes (p=0.15) or TBARS (p=0.38) over time. 96 h following wine ingestion, the mean conjugated dienes were 12.1+/-4.12 micromol/l and mean TBARS were 16.4+/-8.8 micromol/l (pooled data, n=60). CONCLUSION: Ingestion of 300 ml wine does not protect LDL from oxidation in vivo in healthy subjects. However, this does not exclude an effect of habitual wine consumption on LDL plasma oxidation.

Pharmacology. 2005 Nov;75(3):152-6

Red wine reduces oxidative stress in patients with acute coronary syndrome.

BACKGROUND: Moderate red wine consumption improved endothelial function in normal volunteers. Herein we explored the effects of moderate red wine consumption in endothelial function and in oxidative stress in patients with an acute coronary syndrome. METHODS: 20 patients treated with percutaneous coronary interventions after an acute coronary syndrome were randomized to a red-wine group (n=9, 250 ml daily, Cabernet Sauvignon) or to a control group (n=11, abstinence from alcoholic beverages). Studies were performed at baseline and after 2 months. Endothelial function was estimated by flow-mediated vasodilatation of the brachial artery. Plasma antioxidant capacity was measured by total antioxidant reactivity and ferric reducing antioxidant power. Oxidative damage was evaluated by measurements of 8-OH deoxyguanosine content in leukocyte deoxyribonucleic acid. RESULTS: The endothelium dependent/independent dilatation ratio significantly improved compared to baseline in both groups. The 8-OH deoxyguanosine content decreased significantly in both groups; this effect was more pronounced with wine (p<0.002 vs. control). Oxidative deoxyribonucleic acid damage in controls decreased from 13.1+/-1.1 to 10.0+/-1.0 (p<0.003); with wine from 13+/-0.8 to 5.6+/-0.7 per 10(5) guanosines (p<0.001; p<0.002 vs. control). Total antioxidant reactivity increased from 240+/-18 to 268+/-18 microM in the control group and from 273+/-20 to 330+/-15 microM in the wine group (p<0.03 vs. control). Ferric reducing antioxidant power increased from 1106+/-60 to 1235+/-42 microM in the control group and from 1219+/-82 to 1450+/-63 microM in the wine group (p<0.001 vs. control). CONCLUSIONS: The addition of moderate amounts of red wine did not improve endothelial function beyond conventional therapy, whereas it showed benefits in parameters of oxidative stress in these patients.

Int J Cardiol. 2005 Sep 15;104(1):35-8

Effect of moderate red wine intake on cardiac prognosis after recent acute myocardial infarction of subjects with Type 2 diabetes mellitus.

BACKGROUND: Oxidative stress and increased inflammation have been reported to be increased in subjects with diabetes and to be involved in the pathogenesis of cardiovascular complications after myocardial infarction (MI). It is well recognized that red wine has antioxidant and anti-inflammatory activities. We examined the effects of moderate red wine intake on echocardiographic parameters of functional cardiac outcome in addition to inflammatory cytokines and nitrotyrosine (oxidative stress marker), in subjects with diabetes after a first uncomplicated MI. METHODS: One hundred and fifteen subjects with diabetes who had sustained a first non-fatal MI were randomized to receive a moderate daily amount of red wine (intervention group) or not (control group). Echocardiographic parameters of ventricular dys-synchrony, circulating levels of nitrotyrosine, tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-18 (IL-18) and C-reactive protein (CRP) were investigated at baseline and 12 months after randomization. RESULTS: After 1 year of diet intervention, concentrations of nitrotyrosine (P < 0.01), CRP (P < 0.01), TNF-alpha (P < 0.01), IL-6 (P < 0.01) and IL-18 (P < 0.01) were increased in the control group compared with the intervention group. In addition, myocardial performance index (P < 0.02) was higher, and transmitral Doppler flow (P < 0.05), pulmonary venous flow analysis (P < 0.02) and ejection fraction (P < 0.05) were lower in the control group, indicating ventricular dys-synchrony. The concentrations of nitrotyrosine, CRP, TNF-alpha and IL-6 were related to echocardiographic parameters of ventricular dys-synchrony. CONCLUSIONS: In subjects with diabetes, red wine consumption, taken with meals, significantly reduces oxidative stress and pro-inflammatory cytokines as well as improving cardiac function after MI. Moderate red wine intake with meals may have a beneficial effect in the prevention of cardiovascular complications after MI in subjects with diabetes.

Diabet Med. 2006 Sep;23(9):974-81

Polyphenolic compounds from red grapes acutely improve endothelial function in patients with coronary heart disease.

BACKGROUND: It has been shown that acute intake of red wine improves endothelial-dependent vasodilatation. It is not clear, however, which constituents of red wine are responsible for this effect. We examined whether acute intake of a red grape polyphenol extract has a positive effect on brachial artery flow-mediated dilatation. METHODS: We recruited 30 male patients with coronary heart disease. They were randomly assigned either to a red grape polyphenol extract (600 mg) dissolved in 20 ml of water (n = 15) or 20 ml of water (placebo) (n = 15). The extract of grapes contained 4.32 mg epicatechin, 2.72 mg catechin, 2.07 mg gallic acid, 0.9 mg trans-resveratrol, 0.47 mg rutin, 0.42 mg epsilon-viniferin, 0.28 mg, p-coumaric acid, 0.14 mg ferulic acid and 0.04 mg quercetin per gram. Flow-mediated dilatation of the brachial artery was evaluated after reactive hyperemia induced by cuff obstruction of the forearm, using high-resolution ultasonography. Particularly, flow-mediated dilatation was measured after fasting and 30, 60 and 120 min after the intake of the grape extract or placebo. RESULTS: Intake of the red grape polyphenol extract caused an increase in flow-mediated dilatation, peaking at 60 min, which was significantly higher than the baseline values (4.52+/-1.34 versus 2.6+/-1.5%; P < 0.001) and the corresponding values at 60 min after the intake of placebo (4.52+/-1.34 versus 2.64+/-1.8%, P < 0.001). There was no change in FMD values after the intake of placebo throughout the whole duration of the study. CONCLUSION: Polyphenolic compounds from red grapes acutely improve endothelial function in patients with coronary heart disease. These results could probably, at least partly, explain the favorable effects of red wine on the cardiovascular system.

Eur J Cardiovasc Prev Rehabil. 2005 Dec;12(6):596-600

Red wine induced modulation of vascular function: separating the role of polyphenols, ethanol, and urates.

By using red wine (RW), dealcoholized red wine (DARW), polyphenols-stripped red wine (PSRW), ethanol-water solution (ET), and water (W), the role of wine polyphenols, ethanol, and urate on vascular function was examined in humans (n = 9 per beverage) and on isolated rat aortic rings (n = 9). Healthy males randomly consumed each beverage in a cross-over design. Plasma ethanol, catechin, and urate concentrations were measured before and 30, 60 and 120 minutes after beverage intake. Endothelial function was assessed before and 60 minutes after beverage consumption by normalized flow-mediated dilation (FMD). RW and DARW induced similar vasodilatation in the isolated vessels whereas PSRW, ET, and W did not. All ethanol-containing beverages induced similar basal vasodilatation of brachial artery. Only intake of RW resulted in enhancement of endothelial response, despite similar plasma catechin concentration after DARW. The borderline effect of RW on FMD (P = 0.0531) became significant after FMD normalization (P = 0.0043) that neutralized blunting effect of ethanol-induced basal vasodilatation. Effects of PSRW and ET did not differ although plasma urate increased after PSRW and not after ET, indicating lack of urate influence on endothelial response. Acute vascular effects of RW, mediated by polyphenols, cannot be predicted by plasma catechin concentration only.

J Cardiovasc Pharmacol. 2006 May;47(5):695-701

The effect of chronic consumption of red wine polyphenols on vascular function in postmenopausal women.

OBJECTIVE: To elucidate whether the chronic consumption of dealcoholised red wine (DRW) (polyphenol-rich component) and/or red wine (RW) improves vascular function in hypercholesterolaemic postmenopausal women. DESIGN, SUBJECTS AND INTERVENTION: A randomised parallel-arm study. Forty-five hypercholesterolaemic postmenopausal women were randomised into either water, DRW or RW group for 6 weeks following a 4 week washout. Fasting measures of central haemodynamic parameters, arterial wave reflection and endothelial nitric oxide were taken at 0 and 6 weeks. SETTING: Clinic in the School of Public Health, Curtin University. RESULTS: There were no significant between group differences in arterial stiffness as measured by augmentation index (AIx) and augmentation pressure (AP). However, a significant within group decrease in AIx (-9%, P=0.02) and AP (-12%, P=0.02) was observed following DRW consumption. No significant changes were observed in central haemodynamic parameters and endothelial nitric oxide levels following DRW and RW consumption, compared to water. CONCLUSIONS: Neither the chronic consumption of DRW nor RW improved markers of arterial stiffness, compared to control. However, the significant within group improvements in these indices following the consumption of DRW cannot be overlooked and warrant further investigation.

Eur J Clin Nutr. 2006 Jun;60(6):740-5

Effects of armagnac or vodka on platelet aggregation in healthy volunteers: a randomized controlled clinical trial.

BACKGROUND: Cardiovascular mortality is especially low in southwest France (the French Paradox). In previous experimental studies, we found that alcohol-free extracts of armagnac could inhibit human platelet function in vitro and experimental thrombosis in vivo. To test the possible relevance of these findings, we tested the effects of daily use of small quantities of armagnac against same alcohol strength, polyphenol-free vodka in healthy volunteers. METHOD: Randomized controlled trial comparing 5-year-old armagnac (30 ml/day for 2 weeks) to same alcoholic strength vodka, in 20 healthy volunteers, on platelet aggregation induced by ADP, collagen, and thrombin, as well as bleeding time, partial thromboplastin time (pTT), and plasma lipids during and after consumption. Platelet testing was done blind. RESULTS: After 14 days, ADP-induced platelet aggregation was inhibited more in armagnac (-31+/-3.2% compared to pretreatment values, p<.01) than in vodka (-11.0+/-6.8%, NS) users (p<.05, armagnac vs. vodka). A rebound increase of aggregation was found 2 weeks later in vodka but not in armagnac users. The same pattern was found for thrombin-induced aggregation, including post-treatment rebound. No effect was found on collagen-induced aggregation, bleeding time, pTT, or plasma lipids. CONCLUSION: The chronic ingestion of moderate quantities of armagnac modified platelet aggregation to ADP in healthy volunteers. The difference with the effects of same alcohol degree vodka is in favour of an effect of the nonalcoholic fraction in the effects of armagnac, rather than just alcohol. All spirits may not be equal for cardioprotection.

Thromb Res. 2005;115(1-2):31-7

Low molecular proanthocyanidin dietary biofactor Oligonol: Its modulation of oxidative stress, bioefficacy, neuroprotection, food application, and chemoprevention potentials.

Interdisciplinary research endeavors are directed at understanding the molecular mechanisms of neurodegenerative and chronic diseases that affect human lifestyle. Hence the potential for developing medicinal herb-derived and food plant-derived prophylactic agents directed at neurological, metabolic, cardiovascular and psychiatric disorders abounds. Oligonol is a novel technology product emanating from the oligomerization of polyphenols, typically proanthocyanidin from a variety of fruits (grapes, apples, persimmons etc.) that has optimized bioavailability. It is an optimized phenolic product containing catechin-type monomers and oligomeric proanthocyanidins, the easily absorbed forms. Typically the constituents of Oligonol are 15-20% monomers, 8-12% dimers and 5-10% trimers. Supplementation of mice with Oligonol prior to the administration of ferric-nitrilotriacetic complex (a Fenton chemistry model) significantly reduced the extent of lipid peroxidation in the kidney, brain and liver. Oligonol triggers apoptosis in the MCF-7 and MDA-MB-231 breast cancer cells through modulation of the pro-apoptotic Bcl-2 family of proteins and the MEK/ERK signaling pathway, an observation suggesting its important chemopreventive effects. The senescence-accelerated strain of mice (SAM) are models of senescence acceleration and geriatric disorders which exhibit learning and memory deficits and enhanced production or defective control of oxidative stress leading.

Biofactors. 2006;27(1-4):245-65

Grape powder polyphenols attenuate atherosclerosis development in apolipoprotein E deficient (E0) mice and reduce macrophage atherogenicity.

The beneficial health effects of red wine have been attributed to the antioxidant activity of its polyphenols. The present study investigated the effects of a standardized freeze-dried powder made from fresh grapes, rich in grape-specific polyphenols and free of alcohol, on oxidative stress, atherogenicity of macrophages, and the development of atherosclerotic lesions in apolipoprotein E deficient (E(0)) mice. Thirty E(0) mice were assigned to 3 groups. Mice consumed water alone (control), 150 mug total polyphenols/d in the form of grape powder (grape powder), or the equivalent amount of glucose and fructose (placebo) in drinking water for 10 wk. Consumption of grape powder reduced the atherosclerotic lesion area by 41% (P < 0.0002) compared to the control or placebo mice. The antiatherosclerotic effect was at least partly due to a significant 8% reduction in serum oxidative stress, an up to 22% increase in serum antioxidant capacity, a significant 33% reduction in macrophage uptake of oxidized LDL, and a 25% decrease in macrophage-mediated oxidation of LDL relative to controls. Grape powder directly protected both plasma LDL and macrophages from oxidative stress in vitro. We conclude that polyphenols from fresh grape powder directly affect macrophage atherogenicity by reducing macrophage-mediated oxidation of LDL and cellular uptake of oxidized LDL. Both of these processes can eventually reduce macrophage cholesterol accumulation and foam cell formation and hence attenuate atherosclerosis development.

J Nutr. 2005 Apr;135(4):722-8