A moderate dose of red wine, but not de-alcoholized red wine increases coronary flow reserve☆
Introduction
Moderate consumption of red wine is associated with reduced coronary artery disease mortality [1], [2]. The cardioprotective effects of red wine may be partly related to its ability to improve endothelial function [3]. Red wine increases the endothelium-dependent flow-mediated dilatation of the brachial artery acutely after ingestion [4], [5], [6]. Moreover, a high dose of red wine (ethanol 1.0 g/kg) has been shown to increase coronary flow velocity reserve (CFR) as measured with transthoracic Doppler echocardiography, whereas pure alcohol and white wine had no such effect [7]. CFR depicts the relative increase of coronary blood flow in response to maximal myocardial hyperemia induced by adenosine. It is reduced in early stages of coronary atherosclerosis [8] and various conditions associated with the dysfunction of coronary microcirculation, such as diabetes [9] and hypercholesterolemia [10].
The beneficial vasodilatory effects of red wine have been attributed to both ethanol and antioxidative polyphenols [11], [12]. However, their relative contributions in vivo remain to be established. Moreover, the bioavailability of the antioxidant content of red wine has not been addressed simultaneously with CFR measurements. It has been suggested that red wine has better vasoactive properties than other alcohol beverages, and even de-alcoholized red wine may be sufficient to improve the flow-mediated dilatation of the brachial artery [4].
The purpose of this randomized controlled cross-over study was to determine with transthoracic echocardiography whether moderate doses of red wine improve CFR in response to adenosine in healthy humans. We also studied the contributions of ethanol and antioxidants by comparing the effects of equal doses of alcoholic and de-alcoholized red wine on plasma antioxidant capacity and CFR.
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Subjects and study protocol
The study included 22 healthy, non-smoking Finnish men (mean age 23 ± 1.8 years, body mass index 24 ± 2.3 kg/m2, total cholesterol 4.2 ± 0.8 mmol/l, HDL cholesterol 1.6 ± 0.41 mmol/l, LDL cholesterol 2.3 ± 0.65 mmol/l, triglycerides 0.77 ± 0.21 mmol/l and plasma glucose 5.0 ± 0.46 mmol/l). None of the subjects were taking any medication. One subject dropped out of the study because of red wine-related headache. The study was carried out in accordance with the Declaration of Helsinki (2000) of the World Medical
CFR
Table 1 shows the effects of the study beverages on coronary mean diastolic velocities. Red wine increased CFR from 3.8 ± 1.4 to 4.5 ± 1.4 (p < 0.01) and 4.0 ± 1.2 (p = NS) after moderate and high doses, respectively (see Fig. 2 and Table 2). De-alcoholized red wine had no significant effects on CFR (4.0 ± 0.7, 4.3 ± 1.3 and 4.5 ± 1.4, respectively).
Antioxidant capacity
Plasma antioxidant capacity increased from 265 ± 35.0 to 333 ± 29.3 μmol/l by 27.5 ± 14.7% (p < 0.001) after red wine. De-alcoholized red wine had no effect on plasma
Discussion
This randomized controlled cross-over study demonstrates that a moderate dose of red wine increases CFR as measured with transthoracic echocardiography. Red wine also increases plasma antioxidant capacity. Despite similar amount of antioxidant polyphenols, de-alcoholized red wine has no effect on either CFR or plasma antioxidant capacity.
A previous study suggested that a high dose of red wine (ethanol 1.0 g/kg) improves CFR [7]. Importantly, improving CFR appeared to be a unique feature of red
Conflict of interest
None.
Acknowledgements
Funding: This study was supported by The Turku University Hospital Research Foundation, the Tampere University Hospital Medical Fund, the Turku University Foundation, the Emil Aaltonen Foundation, the Orionpharma Research Foundation, the Instrumentarium Research Foundation and the Paulo Foundation.
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2012, Journal of Molecular and Cellular CardiologyCitation Excerpt :Apart from improving the cardiovascular risk profile, ethanol also has direct effects on the coronary vasculature to increase myocardial blood flow. Ethanol-induced vasodilation occurs as a result of NO generation secondary to increased nitric oxide synthase (NOS) expression and activity and via activation of transient receptor potential vanilloid 1 (TRPV1) channels on perivascular sensory nerve terminals, which subsequently release the potent vasodilator calcitonin gene-related peptide (CGRP), thereby increasing coronary blood flow [116–119]. Interestingly, polyphenols in red wine also increase NOS activity [120,121] and ingestion of red wine increases brachial artery blood flow in humans [122].
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ClinicalTrials.gov Identifier: NCT00330213.