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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    • "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.
    Current Pharmaceutical Biotechnology 06/2014; 15(4). DOI:10.2174/1389201015666140617101332 · 2.51 Impact Factor
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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.
    Applied Physiology Nutrition and Metabolism 04/2014; 39(10):1-5. DOI:10.1139/apnm-2013-0547 · 2.34 Impact Factor
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    • "Blood samples were collected between 8 and 10 AM at baseline, 6 and 12 months and the corresponding serum or plasma samples were kept at −80 °C until analysis. Serum levels of inflammation-related markers and PAI-1were measured, at least in duplicate, by enzyme-linked immunosorbent assays (ELISA) as previously described [15]. Those determinations that yielded either borderline or statistically significant changes were further repeated to confirm the results. "
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    ABSTRACT: Purpose: The grape and wine polyphenol resveratrol exerts cardiovascular benefits but evidence from randomized human clinical trials is very limited. We investigated dose-depending effects of a resveratrol-containing grape supplement on stable patients with coronary artery disease (CAD) treated according to currently accepted guidelines for secondary prevention of cardiovascular disease. Methods: In a triple-blind, randomized, placebo-controlled, one-year follow-up, 3-arm pilot clinical trial, 75 stable-CAD patients received 350 mg/day of placebo, resveratrol-containing grape extract (grape phenolics plus 8 mg resveratrol) or conventional grape extract lacking resveratrol during 6 months, and a double dose for the following 6 months. Changes in circulating inflammatory and fibrinolytic biomarkers were analyzed. Moreover, the transcriptional profiling of inflammatory genes in peripheral blood mononuclear cells (PBMCs) was explored using microarrays and functional gene expression analysis. Results: After 1 year, in contrast to the placebo and conventional grape extract groups, the resveratrol-containing grape extract group showed an increase of the anti-inflammatory serum adiponectin (9.6 %, p = 0.01) and a decrease of the thrombogenic plasminogen activator inhibitor type 1 (PAI-1) (-18.6 %, p = 0.05). In addition, 6 key inflammation-related transcription factors were predicted to be significantly activated or inhibited, with 27 extracellular-space acting genes involved in inflammation, cell migration and T-cell interaction signals presenting downregulation (p < 0.05) in PBMCs. No adverse effects were detected in relation to the study products. Conclusions: Chronic daily consumption of a resveratrol-containing grape nutraceutical could exert cardiovascular benefits in stable-CAD patients treated according to current evidence-based standards, by increasing serum adiponectin, preventing PAI-1 increase and inhibiting atherothrombotic signals in PBMCs.
    Cardiovascular Drugs and Therapy 12/2012; 27(1). DOI:10.1007/s10557-012-6427-8 · 3.19 Impact Factor
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