One-Year Consumption of a Grape Nutraceutical Containing Resveratrol Improves the Inflammatory and Fibrinolytic Status of Patients in Primary Prevention of Cardiovascular Disease

Research Group on Quality, Safety, and Bioactivity of Plant Foods, CEBAS-CSIC, Murcia, Spain.
The American journal of cardiology (Impact Factor: 3.28). 04/2012; 110(3):356-63. DOI: 10.1016/j.amjcard.2012.03.030
Source: PubMed


The search for complementary treatments in primary prevention of cardiovascular disease (CVD) is a high-priority challenge. Grape and wine polyphenol resveratrol confers CV benefits, in part by exerting anti-inflammatory effects. However, the evidence in human long-term clinical trials has yet to be established. We aimed to investigate the effects of a dietary resveratrol-rich grape supplement on the inflammatory and fibrinolytic status of subjects at high risk of CVD and treated according to current guidelines for primary prevention of CVD. Seventy-five patients undergoing primary prevention of CVD participated in this triple-blinded, randomized, parallel, dose-response, placebo-controlled, 1-year follow-up trial. Patients, allocated in 3 groups, consumed placebo (maltodextrin), a resveratrol-rich grape supplement (resveratrol 8 mg), or a conventional grape supplement lacking resveratrol, for the first 6 months and a double dose for the next 6 months. In contrast to placebo and conventional grape supplement, the resveratrol-rich grape supplement significantly decreased high-sensitivity C-reactive protein (-26%, p = 0.03), tumor necrosis factor-α (-19.8%, p = 0.01), plasminogen activator inhibitor type 1 (-16.8%, p = 0.03), and interleukin-6/interleukin-10 ratio (-24%, p = 0.04) and increased anti-inflammatory interleukin-10 (19.8%, p = 0.00). Adiponectin (6.5%, p = 0.07) and soluble intercellular adhesion molecule-1 (-5.7%, p = 0.06) tended to increase and decrease, respectively. No adverse effects were observed in any patient. In conclusion, 1-year consumption of a resveratrol-rich grape supplement improved the inflammatory and fibrinolytic status in patients who were on statins for primary prevention of CVD and at high CVD risk (i.e., with diabetes or hypercholesterolemia plus ≥1 other CV risk factor). Our results show for the first time that a dietary intervention with grape resveratrol could complement the gold standard therapy in the primary prevention of CVD.

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Available from: María Teresa García-Conesa, Jun 06, 2014
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    • "Homeostasis of the vascular endothelium, in terms of both metabolic and physiological activities, is subject to fine-tuning by individual nutrients or nutrient derivatives [4] [5]. Grape skin or seeds are very rich source of polyphenols, especially flavanols with proanthocyanidins [6], and other compounds with antioxidant and anti-inflammatory activities resembling those of resveratrol [7] [8]. Many studies confirm the cardioprotective effects of grape seeds, demonstrating reduction of blood pressure, lower levels of oxidized low-density lipoprotein (ox-LDL), and enhanced nitric oxide (NO) production [9] [10] [11] [12]. "
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    ABSTRACT: Purpose Numerous studies have suggested that grape seed extract (GSE) confers vascular protection due to the direct effect of its polyphenol content on endothelial cells. The aim of the study was to determine whether GSE confers vascular protection through the direct effect of its polyphenol content on endothelial cells. Material/methods After incubation with GSE-treated human umbilical vein endothelial cells (HUVECs), blood platelet reactivity was evaluated with regard to the expression of CD62P and the activated form of GPIIbIIIa in ADP-stimulated platelets. Results Lower concentrations of GSE were found to enhance the antiplatelet action of HUVECs: 1 μg/ml GSE reduced platelet reactivity by about 10%. While platelet reactivity was not altered by HUVECs incubated with higher concentrations of GSE, HUVEC proliferation was significantly reduced by GSE of up to 10 μg gallic acid equivalent/ml. Conclusions The results of the study show that low doses of GSE potentiate the inhibitory action of HUVECs on platelet reactivity, which may account, at least partially, for the protective effects of grape products against cardiovascular diseases. In contrast, high concentrations of GSE significantly impair endothelial cell proliferation in vitro.
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    • "Several clinical trials have enlightened resveratrol's ability to attenuate certain aspects of metabolic diseases, such as obesity [89], T2DM [90], T2DM associated with hypertension [91] and cardiovascular disease [92], among others. Investigating its anti-inflammatory role in the CNS in similar pathological contexts helps in achieving a broader portrayal of resveratrol's beneficial effects in metabolic diseases. "
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    ABSTRACT: Under normal conditions, most of the central nervous system (CNS) is protected by the blood brain barrier (BBB) from systemic inflammation progression and from the infiltration of immune cells. As a consequence, the CNS developed an original way to provide surveillance, defense and repair, which relies on the complex process of neuroinflammation. Despite tight regulation, neuroinflammation is frequently the cause of irreversible nerve cell loss but it is also where the solution lies. Specific immune crosstalk taking place in the CNS needs to be decoded in order to identify the best therapeutic strategies aimed at helping the CNS restore homeostasis in difficult conditions such as is the case in neurodegenerative disorders. This review deals with the double-edged sword nature of neuroinflammation and the use of resveratrol in various models as one of the most promising therapeutic molecules for preventing the consequences of nerve cell auto-destruction.
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    • "The impact of a longer treatment period on liver function is unknown. We did not find any beneficial effects on lipid profile or anti-inflammatory effect with resveratrol which is in contrast to the literature (Timmers et al. 2011; Tomé-Carneiro et al. 2012). In this study we did observe a small reduction in fasting glucose following resveratrol supplementation. "
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    ABSTRACT: To assess the effect on exercise capacity and tolerability of resveratrol, 13 healthy, sedentary adult volunteers were enrolled in a randomized crossover study comparing resveratrol and placebo over two 4-week periods, with a 2-week time between periods when subjects received no treatment. No significant changes in exercise duration or aerobic capacity (peak oxygen uptake) were observed. Gastrointestinal side effects were more common during resveratrol treatment (77% vs. 15%, p = 0.0048). A small reduction in fasting glucose and small but statistically significant increases in liver enzymes, total cholesterol, and triglycerides were observed, although mean results remained within normal limits. There was no change in complete blood count, inflammatory markers, renal function, or other measures of liver function.
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