Review articles

The effects of wine consumption on cardiovascular disease and associated risk factors: a narrative review

Abstract

Accumulating evidence suggests that regular moderate consumption of wine can positively influence risk factors associated with cardiovascular health. These effects are often attributed to grape and wine-derived phenolic compounds and their effects on risk factors such as atherosclerosis, for which mechanisms have been clearly identified, such as a decrease in the oxidation of LDL-cholesterol and reduction of oxidative stress, and an increase in nitric oxide and related restoration of endothelial function. In addition, the ethanol component of wine increases HDL-cholesterol, inhibits platelet aggregation, promotes fibrinolysis and reduces systemic inflammation. Scientific research needs to be conducted, however, before we can begin to provide science-based dietary recommendations, although there is sufficient evidence to generally recommend consuming food sources rich in bioactive compounds such as wine in moderation. This narrative review examines published evidence on the cardioprotective effects associated with wine-derived compounds, with a primary focus on the development and progression of atherosclerosis and thrombosis.

Introduction

Cardiovascular events are the primary cause of mortality and morbidity in both developed and developing countries, accounting for approximately 20% of all deaths. Clinical cardiovascular events are mainly of atherothrombotic origin. “Athero-thrombosis” associates two fundamental conditions. Atherosclerosis is where lesions affect the vessel wall of arteries, reducing their medium diameter. Reactive thrombosis occurs on these advanced lesions especially when they rupture. Without thrombotic reactivity, even the most advanced arterial lesion would remain clinically silent. Atherosclerotic lesions are triggered by a genetic background associating numerous metabolic dysfunctions, such as hypercholesterolemia, hyperhomocysteinemia, hyperglycemia and hypertension, together with environmental factors. Thrombotic reactivity depends also on the genetic background and some predisposing conditions, such as hypercoagulability and hyperviscosity. Recently, Stockley (2012) examined the suggestions and evidence surrounding the relationship between light-to-moderate alcohol consumption and human health benefits. Numerous epidemiological studies have demonstrated an inverse correlation between moderate consumption of alcohol and the incidence of coronary artery disease (CAD) and myocardial infarction, in comparison to an increased risk in lifelong abstainers (Kannel 1988; Moore et al., 1990; Shaper et al., 1988). The inclusion of “sick quitters” in the control group in some studies published prior to 2007 had prompted some research groups to suggest that this unduly influenced estimates of the extent of alcohol’s cardioprotection (Fillmore et al., 2007).

In contrast, the large Norwegian Nord-Trøndelag Health (HUNT) study was undertaken in a population characterized by low average alcohol consumption, where abstinence is not socially stigmatized (Gémes et al., 2016a, b). Frequent, light-to-moderate alcohol consumption appeared most cardioprotective and this relationship was not driven by the misclassification of former drinkers. Specifically, there was an inverse correlation between alcohol consumption and risk of CAD and myocardial infarction, as well as heart failure, where frequency of alcohol consumption was more strongly associated with risk than overall quantity consumed. A dose response meta-analysis of 18 prospective studies totalling 214,340 participants and 7,756 CAD cases suggested, however, that the optimum amount of alcohol to reduce risk is 36 g/day (Yang et al., 2016). A subsequent population-based cohort study by Bell et al. (2017) extended the inverse correlation between alcohol consumption and risk to other common cardiovascular diseases including angina, ischaemic stroke, peripheral arterial disease, and abdominal aortic aneurysm, and to all-cause mortality. Compared with moderate alcohol consumers (32 g/day for men and 24 g/day for women), abstainers had a 32% increased risk of fatal cardiovascular disease and a 24% increased risk of all-cause mortality and, similarly, heavy alcohol consumers.

Beneficial effects of moderate consumption of alcoholic beverages on cardiovascular diseases

The vast majority of epidemiological studies consistently show that moderate consumption of alcoholic beverages is associated with a reduced incidence of mortality from different cardiovascular diseases by 20 to 50% compared to lifelong abstainers (Boffetta and Garfinkel, 1990; Camargo et al., 1997a; Doll et al., 1994; Marmot and Brunner 1991). This is particularly true for those individuals with one or more risk factors for cardiovascular diseases such as hypertension, cigarette smoking, hypercholesterolemia, obesity and diabetes (Camargo et al., 1997b; de Gaetano et al., 2016; di Castelnuovo et al., 2017; Gronbaek et al., 1994). However, it is still in dispute whether any one of the three types of alcoholic beverages ─ wine, beer or spirits ─ is more cardioprotective than the others (di Castelnuovo et al., 2009; Perissinotto et al., 2010). A review by Rimm et al. (1996) concluded that all alcoholic beverages were associated with lower risk, and the beneficial effects on coronary heart disease (CHD) could be attributed to the common alcohol component itself. However, a meta-analysis by de Gaetano et al. (2016) confirmed the J-shaped association between wine consumption and vascular risk and provided evidence for a similar relationship for beer. In a meta-analysis of 10 studies on spirit consumption and vascular risk, no J-shaped relationship could be found (Costanzo et al., 2011).

Most of these investigations were based on populations consuming one predominant type of alcoholic beverage, which precluded valid comparison of the effects of the three different types of alcoholic beverages. Earlier epidemiological and clinical studies of alcoholic beverages suggested that wine consumption might confer additional benefits (Renaud and de Lorgeril, 1992; Renaud et al., 1999; Rotondo and de Gaetano 2000) and several more recent studies have also been published giving individual relative risks attributable to the consumption of wine, beer or spirits. Many of these have shown that wine drinkers had a lower risk for death from CHD than did non-wine drinkers at all levels of total alcohol consumption (di Castelnuovo et al., 2002; Farchi et al., 1992; Friedman and Kimball, 1986; Gronbaek et al., 1995; Gronbaek et al., 2000; Klatsky, 2003; Klatsky et al., 1990; Renaud et al., 1998).

Animal and human clinical studies have, however, suggested that the polyphenols found in abundance in fruits and tea, as well as in wine, may reduce the risk of death from CHD by delaying the development if its precursor atherosclerosis.

Animal studies supporting a protective effect of wine against athero-thrombosis

Much experimental evidence supports a protective role of dietary phenolic compounds against cardiovascular diseases such as atherosclerosis (Arts and Hollman, 2005), and it is widely hypothesized that they protect against atherosclerosis by preventing one or more of the processes involved in disease progression, such as oxidative stress, inflammation, and endothelial dysfunction.

Atherosclerosis progresses when macrophages in the sub-endothelial space of an artery take up oxidized low density lipoprotein (LDL) through a non-regulated scavenger receptor and are converted to foam cells which contain excessive lipids, especially cholesterol ester. The continuing aggregation of foam cells and cholesterol esters in the sub-endothelial space leads to the formation of fatty streaks, which are the earliest identifiable lesions of atherosclerosis (referred to as early atherosclerosis).

Polyphenols appear to exert both direct anti-oxidation effects, which include direct reactive oxygen species (ROS) scavenging activity and transient metal chelation, and indirect effects to prevent the development and progression of atherosclerosis (Mladěnka et al., 2010). Three polyphenols in particular (+)-catechin, quercetin (Qer) and resveratrol (Res), have been shown to prevent in vitro and in vivo LDL free radical-mediated oxidation (Frankel et al., 1993, Teissedre et al., 1996). Several animal studies also suggested, however, that while red wine extract and catechin (Cat) did not prevent atherosclerotic lesions, a highly significant reduction of thrombotic reactivity was observed with administration of red wine and Cat (Bentzon et al., 2001; Soulat et al., 2006).

Auger et al. (2005) subsequently studied the effects of Cat, Qer and Res on early atherosclerosis in hamsters. Hamsters (n = 32) were divided into four groups of eight and fed an atherogenic diet for 12 weeks, also receiving once a day either tap water (control) or a solution of Cat, Qer or Res in water (total volume of 7.14 mL/kg body wt/day). The doses of phenolic compounds used were 2.856 mg of (+)-catechin/kg body wt/day, 0.1428 mg of quercetin/kg body wt/day, and 0.1428 mg of resveratrol/kg body wt/day, which mimics moderate consumption of alcohol-free red wine, approximately equivalent to that supplied by the consumption of about two glasses of red wine per meal for a 70 kg human adult. Plasma cholesterol concentration was lower in the groups that consumed the phenolic compounds than in the control group. The increase in plasma apolipoprotein (Apo) A1 concentration was mainly due to Cat (26%) and Qer (22%) and, to a lesser but not significant extent, Res (19%). ApoB was not affected. Plasma antioxidant capacity was not improved, and there was no sparing effect on plasma vitamins A and E. Plasma iron and copper concentrations were not modified, nor were liver super oxide dismutase and catalase activities. A sparing effect of Qer on liver glutathione peroxidase activity appeared, whereas Cat and Res exhibited a smaller effect. Aortic fatty streak area was significantly reduced in the groups receiving Cat (84%), Qer (80%) or Res (76%) in comparison with the control group. These findings demonstrated that Cat, Qer and Res at nutritional doses prevent the development of atherosclerosis through several indirect mechanisms.

Auclair et al. (2009) investigated the anti-atherosclerotic effects of Cat alone supplemented in the diet of ApoE deficient mice. After six weeks of supplementation, atherosclerotic lesions were assessed by histomorphometry and several markers of lipid, inflammation and oxidative stress status were evaluated. Cat supplementation reduced the mean atherosclerotic lesion area by 32% but had no effect on total cholesterol and triacylglycerol levels in plasma and liver. Also, markers such as the plasma antioxidant capacity (FRAP) and the inflammatory status (serum amyloid A) were unchanged. The expression of 450 genes, however, was significantly modified by Cat supplementation. Some of the most significantly down-regulated genes included those coding for adhesion molecules such as CD34 and PSGL-1, which are known to play a key role in leukocyte adhesion to the endothelium. Other genes involved in energy metabolism, lipid metabolism and lipid trafficking such as FABP4, LPL and SCARA5 were also down-regulated and may contribute to the atheroprotective effect of Cat.

Other potential indirect effects of polyphenols that in pharmacologically achievable concentrations may also be responsible for their positive cardiovascular influence include direct inhibition of some radical-forming enzymes (xanthine oxidase, NADPH oxidase and lipoxygenases), decreased platelet aggregation and leukocyte adhesion, and vasodilatory properties, each of which requires specific structural features. For example, a catecholic B-ring is necessary for scavenging activity; hydroxyl groups in an ortho position, the 3-hydroxy-4-keto group, or the 5-hydroxy-4-keto group enable iron chelation; planar conformation with the 4-keto group and 2,3-double bond is essential for inhibition of leukocyte adhesion and platelet aggregation; specific hydroxy-methoxy ortho conformation in ring B is necessary for the inhibition of NADPH oxidase; and the 4-keto group is a requisite for vasodilatory action.

Loke et al. (2010) investigated whether individual dietary polyphenols representing different classes of polyphenol compounds could inhibit the development of atherosclerosis and, specifically, reduce atherosclerotic lesion formation in the ApoE-/- gene-knockout mouse. The polyphenols investigated ─ Qer (flavonol) (-)-epicatechin (flavan-3-ol), theaflavin (dimeric catechin), sesamin (lignan), and chlorogenic acid (phenolic acid) ─ were incorporated into the diet and given at a dose corresponding to achievable human intake. Qer and theaflavin (64 mg/kg body mass/day) significantly attenuated atherosclerotic lesion size in the aortic sinus and thoracic aorta (P<0.05 versus ApoE-/- control mice). Qer significantly reduced aortic F2-isoprostane, vascular superoxide, vascular leukotriene B4, and plasma-sP-selectin concentrations, and increased vascular endothelial nitric oxide (NO) synthase activity, heme oxygenase-1 protein, and urinary nitrate excretion (P<0.05 versus ApoE-/- control mice). Theaflavin showed similar, although less extensive, significant effects. Although (-)-epicatechin significantly reduced F2-isoprostane, superoxide, and endothelin-1 production (P<0.05 versus ApoE-/- control mice), it had no significant effect on lesion size. Sesamin and chlorogenic acid treatments exerted no significant effects. Qer, but not (-)-epicatechin, significantly increased the expression of heme oxygenase-1 protein in lesions versus ApoE-/- controls. The data collectively suggested that dietary polyphenols, and particularly Qer and theaflavin, may attenuate atherosclerosis in ApoE-/- gene-knockout mice by inhibiting inflammation, improving NO bioavailability, and inducing heme oxygenase-1, which was subsequently confirmed by Shen et al. (2013). The data also suggested that inhibition of oxidative stress is generally neither sufficient, nor necessary, for polyphenols to inhibit atherosclerosis in ApoE-/- mice. It was concluded that the cardiovascular protection associated with diets rich in fruits, vegetables and certain beverages may, in part, be the result of flavonoids, such as Qer, through a combination of effects.

Although antioxidants, including phenolic compounds, prevented the development of atherosclerosis in animal models, the observation in human clinical intervention studies that antioxidants such as polyphenols are of no benefit to patients with established atherosclerosis (Steinberg and Witztum, 2002; Steinhubl, 2008; Willcox et al., 2008) led researchers to question whether free radicals are actually involved or responsible for atherogenesis and CHD. Animal model studies have generally used young animals or initiated the intervention when introducing the high-fat or high-carbohydrate diets. Gendron et al. (2010) using a mouse model tested the hypothesis that during aging more severe dyslipidemia leads to the accumulation of endothelial damage that cannot be reversed by an antioxidant treatment. In short, prevention with antioxidants such as Cat is beneficial, whereas intervention is not. To this end, LDLr -/-; hApoB+/+ atherosclerotic (ATX, 9 months old) and pre-ATX (3 months old) male mice were treated with Cat (30 mg/kg/day) up to 12 months of age. At 12 months of age, vascular function and endothelium/leukocyte interactions were studied. Renal artery endothelium-dependent dilations were impaired with age, whereas adhesion of leukocytes onto the native aortic endothelium was increased (P<0.05). Aortic oxidative stress (ROS) increased (P<0.05) at 3 months in ATX and at 12 months in wild-type mice. Aorta mRNA expression of NADPH oxidase increased, whereas that of manganese superoxide dismutase decreased in 12-month-old ATX mice only. In mice with established ATX, Cat (from 9 to 12 months) reduced (P<0.05) by approximately 60% ROS without affecting plaque burden. Notably, Cat worsened endothelial dysfunction and further increased leukocyte adhesion (P<0.05) in ATX mice. In contrast, the same Cat treatment reversed all age-related dysfunctions in wild-type mice. On the other hand, in pre-ATX mice treated for 9 months with Cat, plaque burden was reduced by 64% (P<0.05) and all vascular markers were normalized to the 3-month-old values.

Consequently, it can be hypothesized that regular and moderate wine consumption reduces the incidence of ischaemic cardiovascular events, not primarily by effects on arterial lesions but by effects on thrombotic reactivity. In contrast, heavy wine consumption is an established risk factor for hypertension and the development and progression of atherosclerosis, and is associated with lower fibrinolytic activity, pro-coagulation events, and higher blood viscosity (Toth et al., 2014). For example, alcohol-induced oxidative stress/ROS production, accumulation of fatty acid ethyl esters, modification of lipoproteins, as well as increased expression of pro-inflammatory cytokines and vascular cellular adhesion molecules, all contribute to and promote the formation of atherosclerotic plaques (Hannuksela et al., 2002). In addition, the alcohol-induced increase in blood pressure may counteract direct atheroprotective mechanisms.

Pathophysiological explanations

The cardioprotective effects of alcohol, substantially identical irrespective of the type of alcoholic beverage, can be distinguished from the effects of exclusive wine components, such as polyphenols. These different effects may in part explain the greater reduction in risk noted in many studies with wine when compared to other alcoholic beverages, and include serum lipid changes and anti-oxidation activity, effects on haemostasis and fibrinogen, anti-inflammation, endothelial or vascular function, and others described as follows.

1. Serum lipids

The most recognized and probably the most important mechanism to explain the role of alcohol in preventing CHD is the increased rate of high density lipoprotein (HDL), its different fractions (HDL2 and HDL3), and components (ApoA1 and ApoA2). Moreover, in all prospective studies that assessed the levels of HDL (or its fractions), HDL is negatively correlated with the risk of ischaemic heart disease. Conversely, heavy alcohol consumption elevates serum triglycerides, thereby potentially increasing vascular risk, most probably due to a genetic predisposition (de Oliveira e Silva et al., 2000; Gaziano et al., 1993; Nishiwaki et al., 1994).

2. Anti-oxidation

The inverse relationship between dietary flavonoid consumption and cardiovascular diseases may be associated with the ability of wine polyphenols to attenuate LDL oxidation, macrophage foam cell formation and atherosclerosis (Frankel et al., 1993; Teissedre et al., 1996). The effect of wine polyphenols on arterial cell-mediated oxidation of LDL is determined by their accumulation in the lipoprotein and in arterial cells, such as macrophages. Wine polyphenols can reduce LDL lipid peroxidation by scavenging reactive oxygen/nitrogen species. Since wine seems to be more effective as antioxidant than other alcoholic beverages, many authors have sought to demonstrate that this was the result of the high content of antioxidant compounds in wine. Indeed, wine contains many compounds, including Qer, Cat and Res, all of which have antioxidant properties in vitro (Frankel et al., 1993; Mikstacka et al., 2010; Pinzani et al., 2010; Sun et al., 2009). Red, but not white wine, inhibits the oxidation of human LDL in vitro, presumably due to the difference in polyphenol content. Oxidation of the polyunsaturated lipid components of LDL with ROS may have a role in atherosclerosis.

Red wine is also able to prevent fat oxidation during digestion, which is a novel means to lower the damaging effects of these oxidized fats from, for example, beef meat, on the cardiovascular system (van Hecke et al., 2016). Apparently, wine procyanidins are particularly active in preventing lipid oxidation of food while in the digestive tract, thus preventing the postprandial plasma rise in oxidants. The likely limited bioavailability of these compounds, therefore, does not affect their relevance as key elements for optimizing nutrition and reducing risk of atherogenesis (Covas et al., 2010; Modun et al., 2008; Tsang et al., 2005). Indeed, many researchers consider the GI tract as the major site of action of nutritional antioxidants where they may act as chemical antioxidants. In that way, wine polyphenols may prevent the production and absorption of toxic products of lipid oxidation, thereby counteracting postprandial oxidative and associated damaging inflammatory responses (Gorelik et al., 2008; Halliwell et al., 2000; Ursini and Sevanian, 2002). In contrast to the GI tract, at systemic level in cells, basic kinetic considerations rule out scavenging of radicals as effective antioxidant defense. Instead, polyphenols may function through their metabolism in cells to electrophiles that induce antioxidant enzymes and elevate concentration of the nucleophiles, thereby improving cellular resilience to oxidative stress (Forman and Ursini, 2014; Forman et al., 2014; Plauth et al., 2016).

In addition, wine consumption is associated with moderate and transient elevation in plasma uric acid, the most abundant antioxidant in human plasma, which may significantly contribute to the postprandial antioxidative effects of wine (Modun et al., 2008).

3. Haemostasis

Another explanation for the protective action of alcohol pertains to its effect on platelets, which play a critical role in thrombosis and the pathogenesis of atherosclerosis. Numerous studies have shown that alcohol inhibits platelet aggregation, a key step in haemostasis, in humans as well as in animals in response to several agonists, such as collagen, thrombin, adenosine diphosphate (ADP) and platelet activating factor (PAF). Studies that have investigated the effect of wine and wine polyphenols on platelet activation and aggregation have also shown a significant inhibitory effect on ADP and thrombin-induced platelet aggregation (Crescente et al., 2009; Keevil et al., 2000; Meade et al., 1979; Renaud et al., 1992). Using ADP and thrombin as agonists, Qer and Res both exhibit a dose-dependent inhibition of human platelet aggregation (Bertelli et al., 1996; Pace-Asciak et al., 1995). Another anti-thrombotic effect of wine and wine polyphenols is their capacity to prevent the potentially damaging rebound overshoot of platelet aggregation after withdrawal of alcohol, which partly explains the increase in sudden deaths and haemorrhagic strokes at the end of a weekend or holiday following a binge pattern of alcohol consumption beforehand (Ruf, 2004; Ruf et al., 1995).

4. Fibrinogen

An increase in plasma fibrinogen is generally considered an independent risk factor for atherosclerosis and cardiovascular disease (Koenig et al., 1998). Fibrinogen is, due to its size, shape and high plasma concentration, a major determinant of plasma viscosity. In a recent prospective epidemiological study, the consumption of alcoholic beverages, and particularly wine and spirits, was strongly associated with the concentration of fibrinogen in plasma. This association was J- or a U-shaped where plasma fibrinogen concentration was highest for both non-drinkers and those who drank more than 60 g/day of alcohol (de Curtis et al., 2005; de Lange et al., 2004; Estruch et al., 2004; Hansen et al., 2005, Imhof et al., 2004, Karatzi et al., 2004; Mezzano, 2004; Mezzano and Leighton, 2003).

5. Anti-inflammation

Activated platelets not only facilitate further platelet accumulation but may also recruit polymorphonuclear (PMN) and mononuclear leukocytes by expressing specific adhesive proteins like P-selectin, a receptor mediating platelet-leukocyte binding (Djurovic et al., 2007; Sacanella et al., 2007). There is growing evidence that wine polyphenols may have anti-inflammatory effects. The grape and wine component resveratrol inhibits adhesion molecule expression and monocyte adhesion in vitro (Naito et al., 2004, Williams et al., 2004). Studies provided information showing that wine polyphenols inhibit PMN and mononuclear leukocytes adhesion to stimulated platelets in a dose-dependent manner. This inhibition is due to the reduction by the wine polyphenols of the expression of adhesion molecule such as β2-integrin (MAC-1). More recently, it has been shown that gallic acid, an abundant red wine polyphenol, antagonizes P-selectin-mediated platelet-leukocyte interactions (Carluccio et al., 2003; Estruch et al., 2004; Ferrero et al., 1998).

6. Vascular function

Endothelium-derived NO is an important regulator of vascular tone. Many studies have provided direct evidence that wine polyphenols induce an endothelial-dependent relaxation via a direct enhancement of endothelial NO synthesis (Brizic et al., 2009; Chalopin et al., 2010; de Gaetano et al., 2002; Ndiaye et al., 2005; Sarr et al., 2006). In addition to its vasodilator properties, NO can convey vasoprotection in several ways. NO released toward the vascular lumen is a potent inhibitor of platelet aggregation and adhesion to the vascular wall. Besides protection from thrombosis, this also prevents the release of platelet-derived growth factors that stimulate smooth muscle proliferation and its production of matrix molecules. Endothelial NO also controls the expression of genes involved in atherogenesis. NO decreases the expression of the chemoattractant protein MCP-1, and of surface adhesion molecules such as CD11/CD18, P-selectin, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1), thereby preventing leukocyte adhesion to vascular endothelium and leukocyte migration into the vascular wall (Duarte et al., 2004; Novakovic et al., 2006; Wang et al., 2006). Considering the whole family of polyphenols and stilbenes compounds, it appears that resveratrol protects the cardiovascular system by mechanisms that include defense against ischaemic-reperfusion injury, promotion of vasorelaxation, protection and maintenance of intact endothelium, anti-atherosclerotic properties, inhibition of LDL oxidation, suppression of platelet aggregation, and estrogen-like actions.

7. Other effects

Plasma viscosity is influenced by diseases with altered plasma protein composition, and higher platelet membrane microviscosity is another risk factor for atherosclerosis and cardiovascular disease. Red wine polyphenols have an antioxidative effect on the polyunsaturated fatty acids in the platelet lipid membranes that makes them less reactive (Polette et al., 1996), and red wine (but not white wine) consumption has accordingly been shown to reduce platelet membrane microviscosity, where platelet membrane total saturated fatty acids decreased after red wine consumption whereas total unsaturated fatty acids (poly and mono) showed a tendency to increase after red wine consumption. These results may have a synergistic effect in decreasing platelet aggregation (Jensen et al., 2006; Mansvelt et al., 2002). The antioxidant properties of wine polyphenols are also involved in the anti-aggregatory effect. Certain flavonoids, such as catechin or epicatechin, for example, are able to increase and restore endogenous alpha-tocopherol levels or decrease malondialdehyde (MDA) formation, a marker for lipid peroxidation, in platelets co-incubated with docosahexaenoic acid (DHA), a long-chain polyunsaturated fatty acid observed to reduce platelet aggregation (Polette et al., 1996). Flavonoids have specifically been shown to inhibit the non-enzymatic peroxidation of polyunsaturated fatty acids required for the activation of cyclo- and lipoxygenase. By reacting with the reactive compound of the radical, flavonoids stabilize ROS and because of the high reactivity of the hydroxyl group of the flavonoids, the radical is made inactive.

The adipokine adiponectin might represent an important link between insulin resistance, type 2 diabetes, and atherosclerosis. Adiponectin improves insulin sensitivity and has several anti-inflammatory properties (Aldhahi and Hamdy, 2003), where higher concentrations of adiponectin are associated with lower risk of type 2 diabetes (Duncan and Schmidt, 2006; Spranger et al., 2003) and future cardiovascular events (Pischon et al., 2004). Moderate consumption of alcoholic beverages is associated with increased adiponectin concentrations in healthy individuals, in obese males, and in women with impaired glucose tolerance and type 2 diabetes (Beulens et al., 2006; Beulens et al., 2007; Beulens et al., 2008; Sierksma et al., 2004). While the alcohol component common to all alcoholic beverages is associated with increased adiponectin concentrations, the impact of non-alcoholic ingredients such as polyphenols on adiponectin concentrations has been questioned. Experimental and clinical data suggest that sex hormones affect adiponectin concentrations. Among healthy males, the effects of alcohol consumption on sex hormones has been shown to vary by drinking pattern and between beer and wine consumption (Couwenbergs, 1988; Nishizawa et al., 2002; Rinaldi et al., 2006), such that the type of alcoholic beverage consumed and specifically its polyphenol content may differentially affect adiponectin concentrations. Moreover, in an animal model, the chronic consumption of grape-derived polyphenols was found to prevent diet-induced obesity by improving oxidative stress markers such as adipokine secretion (Décordé et al., 2009).

Serum HDL-associated paraoxonase 1 (PON1) reduces oxidative stress in lipoproteins, macrophages and atherosclerotic lesions, whereas paraoxonase 2 (PON2), which is present in tissues but not in serum, acts as an antioxidant at the cellular level. Both PON1 and PON2 protect against the development of atherosclerosis, which may be related to their antioxidant properties. Supplementation with low doses of red wine polyphenols significantly reduced plasma homocysteine levels and restored the hepatic and plasma-decreased PON1 activity induced by chronic hyperhomocysteinemia. Moreover, quercetin and moderate alcohol consumption significantly inhibit the progression of atherosclerosis by up regulating the hepatic expression of the anti-atherogenic gene, PON1, with concomitant increased serum PON1 activity (Leckey et al., 2010; Noll et al., 2009; Rosenblat and Aviram, 2009).

Conclusions

Estruch and Lamuela-Raventos (2014) succinctly summarize the known biological mechanisms behind alcohol’s observed cardioprotective effects. Discrepancies remain, however, regarding the specific effects of different types of beverages on the cardiovascular system, and also whether the possible protective effects of alcoholic beverages are due to their alcohol component (ethanol) or to non-alcoholic components, mainly polyphenols. Recent randomized clinical trials have shown that wine, a polyphenol-rich alcoholic beverage, potentially provides higher antioxidant and anti-inflammatory effects than some spirits such as gin, a polyphenol-free alcoholic beverage. Also, human clinical trials have shown that lower daily wine consumption by women delivers similar cardioprotective effects to men consuming higher amounts of alcohol.

The biological mechanisms of moderate and regular wine consumption that underlie the cardioprotective effects therefore need to be better understood. In particular, effort is needed to define wine consumption in physiologically relevant quantitative units, the dosage and pattern of consumption required to achieve physiologically relevant polyphenol concentrations in body fluids, and thereby to conduct in vivo studies at physiologically relevant concentrations. In addition, a comparison of wine consumption effects in relation to different diet types and lifestyles is required, as well as details of wine consumption in terms of alcohol content, phenolic content and structures, and origins.

Only scientific evidence accumulated from an unbiased selection of epidemiological, extensive animal, cell culture and human clinical studies will not promulgate misinformation. Indeed, all recent population studies show a significant and meaningful reduction in the risk of cardiovascular disease and total mortality from moderate consumption of alcoholic beverages such as wine. Epidemiologists who previously raised concerns of statistical bias have more recently concluded: “For drinkers having one to two drinks per drinking day without episodic heavy drinking, there is substantial and consistent evidence from epidemiological and short-term experimental studies for a beneficial association with ischaemic heart disease (IHD) risk when compared to lifetime abstainers. The alcohol-IHD relationship fulfills all criteria for a causal association proposed by Hill.” (Roerecke and Rehm, 2014).

References

  • Aldhahi W. and Hamdy O., 2003. Adipokines, inflammation, and the endothelium in diabetes. Curr Diab Rep 3: 293–298. doi:10.1007/s11892-003-0020-2
  • Arts I.C. and Hollman P.C., 2005. Polyphenols and disease risk in epidemiologic studies. Am J Clin Nutr 81: 317S–325S. doi:10.1093/ajcn/81.1.317S
  • Auclair S., Milenkovic D., Besson C., Chauvet S., Gueux E., Morand C., Mazur A. and Scalbert A., 2009. Catechin reduces atherosclerotic lesion development in apo E-deficient mice: a transcriptomic study. Atherosclerosis 204: e21–e27. doi:10.1016/j.atherosclerosis.2008.12.007
  • Auger C., Teissedre P.L., Gérain P., Lequeux N., Bornet A., Serisier S., Besançon P., Caporiccio B., Cristol JP. and Rouanet J.M., 2005. Dietary wine phenolics catechin, quercetin, and resveratrol efficiently protect hypercholesterolemic hamsters against aortic fatty streak accumulation. J Agric Food Chem 53: 2015–2021. doi:10.1021/jf048177q
  • Bell S., Daskalopoulou M., Rapsomaniki E., George J., Britton A., Bobak M., Casas J.P., Dale C.E., Denaxas S., Shah AD. and Hemingway H., 2017. Association between clinically recorded alcohol consumption and initial presentation of 12 cardiovascular diseases: population based cohort study using linked health records. BMJ 356: j909. doi:10.1136/bmj.j909
  • Bentzon J.F., Skovenborg E., Hansen C., Møller J., Saint-Cricq de Gaulejac N., Proch J. and Falk E., 2001. Red wine does not reduce mature atherosclerosis in apolipoprotein E-deficient mice. Circulation 103: 1681–1687. doi:10.1161/01.CIR.103.12.1681
  • Bertelli A.A., Giovannini L., Bernini W., Migliori M., Fregoni M., Bavaresco L. and Bertelli A., 1996. Antiplatelet activity of cis-resveratrol. Drugs Exp Clin Res 22: 61–63.
  • Beulens J.W.J., van Beers R.M., Stolk R.P., Schaafsma G. and Hendriks H.F.J., 2006. The effect of moderate alcohol consumption on fat distribution and adipocytokines. Obesity 14: 60–66. doi:10.1038/oby.2006.8
  • Beulens J.W.J., de Zoete E.C., Kok F.J., Schaafsma G. and Hendriks H.F.J., 2007. Effect of moderate alcohol consumption on adipokines and insulin sensitivity in lean and overweight men: a diet intervention study. Eur J Clin Nutr 62: 1098–1105. doi:10.1038/sj.ejcn.1602821
  • Beulens J.W.J., Rimm E.B., Hu F.B., Hendriks H.F.J. and Mukamal K.J., 2008. Alcohol consumption, mediating biomarkers and risk of type 2 diabetes among middle-aged women. Diabetes Care 31: 2050–2055. doi:10.2337/dc08-0814
  • Boffetta P. and Garfinkel L., 1990. Alcohol drinking and mortality among men enrolled in an American Cancer Society prospective study. Epidemiology 1: 342–348. doi:10.1097/00001648-199009000-00003
  • Brizic I., Modun D., Vukovic J., Budimir D., Katalinic V. and Boban M., 2009. Differences in vasodilatory response to red wine in rat and guinea pig aorta. J Cardiovasc Pharmacol 53: 116–120. doi:10.1097/FJC.0b013e31819715aa
  • Camargo C.A., Stampfer M.J., Glynn RJ., Gaziano J.M., Manson J.E., Goldhaber SZ. and Hennekens C.H., 1997a. Prospective study of moderate alcohol consumption and risk of peripheral arterial disease in U.S. male physicians. Circulation 95: 577–580. doi:10.1161/01.CIR.95.3.577
  • Camargo C.A., Hennekens C.H., Gaziano J.M., Glynn R.J., Manson J.E. and Stampfer M.J., 1997b. Prospective study of moderate alcohol consumption and mortality in U.S. male physicians. Arch Intern Med 157: 79–85. doi:10.1001/archinte.1997.00440220083011
  • Carluccio M.A., Siculella L., Ancora M.A., Massaro M., Scoditti E., Storelli C., Visioli F., Distante A. and de Caterina R., 2003. Olive oil and red wine antioxidant polyphenols inhibit endothelial activation: antiatherogenic properties of Mediterranean diet phytochemicals. Arterioscler Thromb Vasc Biol 23: 622–629. doi:10.1161/01.ATV.0000062884.69432.A0
  • Chalopin M., Tesse A., Martínez M.C., Rognan D., Arnal J.F. and Andriantsitohaina R., 2010. Estrogen receptor alpha as a key target of red wine polyphenols action on the endothelium. PLoS One 5: e8554. doi:10.1371/journal.pone.0008554
  • Costanzo S., di Castelnuovo A., Donati M.B., Iacoviello L. and de Gaetano G., 2011. Wine, beer or spirit drinking in relation to fatal and non-fatal cardiovascular events: a meta-analysis. Eur J Epidemiol 26: 833–850. doi:10.1007/s10654-011-9631-0
  • Couwenbergs C.J., 1988. Acute effects of drinking beer or wine on the steroid hormones of healthy men. J Steroid Biochem 31: 467–473. doi:10.1016/0022-4731(88)90317-2
  • Covas M.I., Gambert P., Fitó M. and de la Torre R., 2010. Wine and oxidative stress: up-to-date evidence of the effects of moderate wine consumption on oxidative damage in humans. Atherosclerosis 208: 297–304. doi:10.1016/j.atherosclerosis.2009.06.031
  • Crescente M., Jessen G., Momi S., Höltje HD., Gresele P., Cerletti C. and de Gaetano G., 2009. Interactions of gallic acid, resveratrol, quercetin and aspirin at the platelet cyclooxygenase-1 level. Functional and modelling studies. Thromb Haemost 102: 336–346. doi:10.1160/TH09-01-0057
  • Décordé K., Teissedre P.L., Sutra T., Ventura E., Cristol J.P. and Rouanet J.M., 2009. Chardonnay grape seed procyanidin extract supplementation prevents high-fat diet-induced obesity in hamsters by improving adipokine imbalance and oxidative stress markers. Mol Nutr Food Res 53: 659–666. doi:10.1002/mnfr.200800165
  • De Curtis A., Murzilli S., di Castelnuovo A., Rotilio D., Donati MB., de Gaetano G. and Iacoviello L., 2005. Alcohol-free red wine prevents arterial thrombosis in dietary-induced hypercholesterolemic rats: experimental support for the 'French paradox'. J Thromb Haemost 3: 346–350. doi:10.1111/j.1538-7836.2005.01126.x
  • De Gaetano G., de Curtis A., di Castelnuovo A., Donati M.B., Iacoviello L. and Rotondo S., 2002. Antithrombotic effect of polyphenols in experimental models: a mechanism of reduced vascular risk by moderate wine consumption. Ann N Y Acad Sci 957: 174–188. doi:10.1111/j.1749-6632.2002.tb02915.x
  • De Gaetano G., Costanzo S., di Castelnuovo A., Badimon L., Bejko D., Alkerwi A., Chiva-Blanch G., Estruch R, La Vecchia C., Panico S., Pounis G., Sofi F., Stranges S., Trevisan M., Ursini F., Cerletti C., Donati M.B. and Iacoviello L., 2016. Effects of moderate beer consumption on health and disease: a consensus document. Nutr Metab Cardiovasc Dis 26: 443–467. doi:10.1016/j.numecd.2016.03.007
  • De Lange D.W., Scholman W.L.G., Kraaijenhagen RJ., Akkerman J.W.N. and van de Wiel A., 2004. Alcohol and polyphenolic grape extract inhibit platelet adhesion in flowing blood. Eur J Clin Invest 34: 818–824. doi:10.1111/j.1365-2362.2004.01432.x
  • De Oliveira e Silva E.R., Foster D., McGee Harper M., Seidman C.E., Smith JD., Breslow J.L. and Brinton E.A., 2000. Alcohol consumption raises HDL cholesterol levels by increasing the transport rate of apolipoproteins A-I and A-II. Circulation 102: 2347–2352. doi:10.1161/01.CIR.102.19.2347
  • Di Castelnuovo A., Rotondo S., Iacoviello L., Donati M.B. and de Gaetano G., 2002. Meta-analysis of wine and beer consumption in relation to vascular risk. Circulation 105: 2836–2844. doi:10.1161/01.CIR.0000018653.19696.01
  • Di Castelnuovo A., Costanzo S., di Giuseppe R., de Gaetano G. and Iacoviello L., 2009. Alcohol consumption and cardiovascular risk: mechanisms of action and epidemiologic perspectives. Future Cardiol 5: 467–477. doi:10.2217/fca.09.36
  • Di Castelnuovo A., Costanzo S., Bonaccio M., Rago L., de Curtis A., Persichillo M., Bracone F., Olivieri M., Cerletti C., Donati MB., de Gaetano G., Iacoviello L. and Moli-Sani Investigators, 2017. Moderate alcohol consumption is associated with lower risk for heart failure but not atrial fibrillation. JACC Heart Fail 5: 837–844. doi:10.1016/j.jchf.2017.08.017
  • Djurovic S., Berge K.E., Birkenes B., Braaten Ø. and Retterstøl L., 2007. The effect of red wine on plasma leptin levels and vasoactive factors from adipose tissue: a randomized crossover trial. Alcohol Alcohol 42: 525–528. doi:10.1093/alcalc/agm056
  • Doll R., Peto R., Hall E., Wheatley K. and Gray R., 1994. Mortality in relation to consumption of alcohol: 13 years' observations on male British doctors. BMJ 309: 911–918. doi:10.1136/bmj.309.6959.911
  • Duarte J., Andriambeloson E., Diebolt M. and Andriantsitohaina R., 2004. Wine polyphenols stimulate superoxide anion production to promote calcium signaling and endothelial-dependent vasodilatation. Physiol Res 53: 595–602.
  • Duncan B.B. and Schmidt M.I., 2006. The epidemiology of low-grade chronic systemic inflammation and type 2 diabetes. Diabetes Technol Ther 8: 7–17. doi:10.1089/dia.2006.8.7
  • Estruch R. and Lamuela-Raventos R.M., 2014. Wine, alcohol, polyphenols and cardiovascular disease. Nutr Aging 2: 101–109. doi:10.3233/NUA-140039
  • Estruch R., Sacanella E., Badia E., Antúnez E., Nicolás JM., Fernández-Solá J., Rotilio D., de Gaetano G., Rubin E. and Urbano-Márquez A., 2004. Different effects of red wine and gin consumption on inflammatory biomarkers of atherosclerosis: a prospective randomized crossover trial. Effects of wine on inflammatory markers. Atherosclerosis 175: 117–123. doi:10.1016/j.atherosclerosis.2004.03.006
  • Farchi G., Fidanza F., Mariotti S. and Menotti A., 1992. Alcohol and mortality in the Italian rural cohorts of the Seven Countries Study. Int J Epidemiol 21: 74–81. doi:10.1093/ije/21.1.74
  • Ferrero M.E., Bertelli AE., Fulgenzi A., Pellegatta F., Corsi M.M., Bonfrate M., Ferrara F., de Caterina R., Giovannini L. and Bertelli A., 1998. Activity in vitro of resveratrol on granulocyte and monocyte adhesion to endothelium. Am J Clin Nutr 68: 1208–1214. doi:10.1093/ajcn/68.6.1208
  • Fillmore K.M., Stockwell T., Chikritzhs T., Bostrom A. and Kerr W., 2007. Moderate alcohol use and reduced mortality risk: systematic error in prospective studies and new hypotheses. Ann Epidemiol 17: S16–S23. doi:10.1016/j.annepidem.2007.01.005
  • Forman HJ. and Ursini F., 2014. Para-hormesis: an innovative mechanism for the health protection brought by antioxidants in wine. Nutr Aging 2: 117–124. doi:10.3233/NUA-130033
  • Forman H.J., Davies K.J.A. and Ursini F., 2014. How do nutritional antioxidants really work: nucleophilic tone and para-hormesis versus free radical scavenging in vivo. Free Radic Biol Med 66: 24–35. doi:10.1016/j.freeradbiomed.2013.05.045.
  • Frankel E.N., Kanner J., German J.B., Parks E. and Kinsella J.E., 1993. Inhibition of oxidation of human low-density lipoprotein by phenolic substances in red wine. Lancet 341: 454–457. doi:10.1016/0140-6736(93)90206-V
  • Friedman L.A. and Kimball A.W., 1986. Coronary heart disease mortality and alcohol consumption in Framingham. Am J Epidemiol 124: 481–489. doi:10.1093/oxfordjournals.aje.a114418
  • Gaziano J.M., Buring J.E., Breslow J.L., Goldhaber S.Z., Rosner B., VanDenburgh M., Willett W., Hennekens C.H., 1993. Moderate alcohol intake, increased levels of high-density lipoprotein and its subfractions, and decreased risk of myocardial infarction. N Engl J Med 329: 1829–1834. doi:10.1056/NEJM199312163292501
  • Gémes K., Janszky I., Laugsand LE., László K.D., Ahnve S., Vatten L.J. and Mukamal K.J., 2016a. Alcohol consumption is associated with a lower incidence of acute myocardial infarction: results from a large prospective population-based study in Norway. J Intern Med 279: 365–375. doi:10.1111/joim.12428
  • Gémes K., Janszky I., Ahnve S., László K.D., Laugsand L.E., Vatten L.J., Mukamal K.J., 2016b. Light-to-moderate drinking and incident heart failure ─ the Norwegian HUNT study. Int J Cardiol 203: 553–560. doi:10.1016/j.ijcard.2015.10.179
  • Gendron M.È., Théorêt J.F., Mamarbachi A.M., Drouin A., Nguyen A., Bolduc V., Thorin-Trescases N., Merhi Y. and Thorin E., 2010. Late chronic catechin antioxidant treatment is deleterious to the endothelial function in aging mice with established atherosclerosis. Am J Physiol Heart Circ Physiol 298: H2062–H2070. doi:10.1152/ajpheart.00532.2009
  • Gorelik S., Ligumsky M., Kohen R. and Kanner J., 2008. A novel function of red wine polyphenols in humans: prevention of absorption of cytotoxic lipid peroxidation products. FASEB J 22: 41–46. doi:10.1096/fj.07-9041com
  • Gronbaek M., Deis A., Sorensen T.I.A., Becker U., Borch-Johnsen K., Muller C., Schnohr P. and Jensen G., 1994. Influence of sex, age, body mass index, and smoking on alcohol intake and mortality. BMJ 308: 302–306. doi:10.1136/bmj.308.6924.302
  • Gronbaek M., Deis A., Sorensen T.I.A., Becker U., Schnohr P. and Jensen G., 1995. Mortality associated with moderate intakes of wine, beer, or spirits. BMJ 310: 1165–1169. doi:10.1136/bmj.310.6988.1165
  • Gronbaek M., Becker U., Johansen D., Gottschau A., Schnohr P., Hein HO., Jensen G. and Sorensen TIA., 2000. Type of alcohol consumed and mortality from all causes, coronary heart disease and cancer. Ann Intern Med 133: 411–419. doi:10.7326/0003-4819-133-6-200009190-00008
  • Halliwell B., Zhao K. and Whiteman M., 2000. The gastrointestinal tract: a major site of antioxidant action? Free Radic Res 33: 819–830. doi:10.1080/10715760000301341
  • Hannuksela M.L., Liisanantti MK. and Savolainen M.J., 2002. Effect of alcohol on lipids and lipoproteins in relation to atherosclerosis. Crit Rev Clin Lab Sci 39: 225–283. doi:10.1080/10408360290795529
  • Hansen A.S., Marckmann P., Dragsted LO., Finné Nielsen I.L., Nielsen S.E. and Grønbaek M., 2005. Effect of red wine and red grape extract on blood lipids, haemostatic factors, and other risk factors for cardiovascular disease. Eur J Clin Nutr 59: 449–455. doi:10.1038/sj.ejcn.1602107
  • Imhof A., Woodward M., Doering A., Helbecque N., Loewel H., Amouyel P., Lowe G.D.O. and Koenig W., 2004. Overall alcohol intake, beer, wine, and systemic markers of inflammation in western Europe: results from three MONICA samples (Augsburg, Glasgow, Lille). Eur Heart J 25: 2092–2100. doi:10.1016/j.ehj.2004.09.032
  • Jensen T., Retterstøl L.J., Sandset P.M., Godal H.C. and Skjønsberg O.H., 2006. A daily glass of red wine induces a prolonged reduction in plasma viscosity: a randomized controlled trial. Blood Coagul Fibrinolysis 17: 471–476. doi:10.1097/01.mbc.0000240920.72930.63
  • Kannel W.B., 1988. Alcohol and cardiovascular disease. Proc Nutr Soc 47: 99–110. doi:10.1079/PNS19880018
  • Karatzi K., Papamichael C., Aznaouridis K., Karatzis E., Lekakis J., Matsouka C., Boskou G., Chiou A., Sitara M., Feliou G., Kontoyiannis D., Zampelas A. and Mavrikakis M., 2004. Constituents of red wine other than alcohol improve endothelial function in patients with coronary artery disease. Coron Artery Dis 15: 485–490. doi:10.1097/00019501-200412000-00005
  • Keevil J.G., Osman H.E., Reed J.D. and Folts J.D., 2000. Grape juice, but not orange juice or grapefruit juice, inhibits human platelet aggregation. J Nutr 130: 53–56. doi:10.1093/jn/130.1.53
  • Klatsky A.L., 2003. Drink to your health? Sci Am 288: 74–81. doi:10.1038/scientificamerican0203-74
  • Klatsky A.L., Armstrong M.A. and Friedman G.D., 1990. Risk of cardiovascular mortality in alcohol drinkers, ex-drinkers and nondrinkers. Am J Cardiol 66: 1237–1242. doi:10.1016/0002-9149(90)91107-H
  • Koenig W., Sund M., Filipiak B., Doring A., Lowel H. and Ernst E., 1998. Plasma viscosity and the risk of coronary heart disease: results from the MONICA-Augsburg Cohort Study, 1984 to 1992. Arterioscler Thromb Vasc Biol 18: 768–772. doi:10.1161/01.ATV.18.5.768
  • Leckey L.C., Garige M., Varatharajalu R., Gong M., Nagata T., Spurney C.F. and Lakshman R.M., 2010. Quercetin and ethanol attenuate the progression of atherosclerotic plaques with concomitant up regulation of paraoxonase1 (PON1) gene expression and PON1 activity in LDLR-/- mice. Alcohol Clin Exp Res 34: 1535–1542. doi:10.1111/j.1530-0277.2010.01238.x
  • Loke W.M., Proudfoot J.M., Hodgson J.M., McKinley A.J., Hime N., Magat M., Stocker R. and Croft KD., 2010. Specific dietary polyphenols attenuate atherosclerosis in apolipoprotein E-knockout mice by alleviating inflammation and endothelial dysfunction. Arterioscler Thromb Vasc Biol 30: 749–757. doi:10.1161/ATVBAHA.109.199687
  • Mansvelt E.P., van Velden D.P., Fourie E., Rossouw M., van Rensburg S.J. and Smuts C.M., 2002. The in vivo antithrombotic effect of wine consumption on human blood platelets and hemostatic factors. Ann N Y Acad Sci 957: 329–332. doi:10.1111/j.1749-6632.2002.tb02935.x
  • Marmot M. and Brunner E., 1991. Alcohol and cardiovascular disease: the status of the U shaped curve. BMJ 303: 565–568. doi:10.1136/bmj.303.6802.565
  • Meade T.W., Chakrabarti R., Haines AP., North W.R.S. and Stirling Y., 1979. Characteristics affecting fibrinolytic activity and plasma fibrinogen concentrations. BMJ 1: 153–156. doi:10.1136/bmj.1.6157.153
  • Mezzano D., 2004. Distinctive effects of red wine and diet on haemostatic cardiovascular risk factors. Biol Res 37: 217–224. doi:10.4067/S0716-97602004000200007
  • Mezzano D. and Leighton F., 2003. Haemostatic cardiovascular risk factors: differential effects of red wine and diet on healthy young. Pathophysiol Haemost Thromb 33: 472–478. doi:10.1159/000083848
  • Mikstacka R., Rimando AM. and Ignatowicz E., 2010. Antioxidant effect of trans-resveratrol, pterostilbene, quercetin and their combinations in human erythrocytes in vitro. Plant Foods Hum Nutr 65: 57–63. doi:10.1007/s11130-010-0154-8
  • Mladěnka P., Zatloukalová L., Filipský T. and Hrdina R., 2010. Cardiovascular effects of flavonoids are not caused only by direct antioxidant activity. Free Radic Biol Med 49: 963–975. doi:10.1016/j.freeradbiomed.2010.06.010
  • Modun D., Music I., Vukovic J., Brizic I., Katalinic V., Obad A., Palada I., Dujic Z. and Boban M., 2008. The increase in human plasma antioxidant capacity after red wine consumption is due to both plasma urate and wine polyphenols. Atherosclerosis 197: 250–256. doi:10.1016/j.atherosclerosis.2007.04.002
  • Moore R.D., Levine D.M., Southard J., Entwisle G. and Shapiro S., 1990. Alcohol consumption and blood pressure in the 1982 Maryland Hypertension Survey. Am J Hypertens 3: 1–7. doi:10.1093/ajh/3.1.1
  • Naito Y., Shimozawa M., Manabe H., Kuroda M., Tomatsuri N., Uchiyama K., Takagi T., Yoshida N. and Yoshikawa T., 2004. Inhibitory effects of red wine extracts on endothelial-dependent adhesive interactions with monocytes induced by oxysterols. Biol Res 37: 231–238. doi:10.4067/S0716-97602004000200009
  • Ndiaye M., Chataigneau M., Lobysheva I., Chataigneau T. and Schini-Kerth V.B., 2005. Red wine polyphenol-induced, endothelium-dependent NO-mediated relaxation is due to the redox-sensitive PI3-kinase/Akt-dependent phosphorylation of endothelial NO-synthase in the isolated porcine coronary artery. FASEB J 19: 455–457. doi:10.1096/fj.04-2146fje
  • Nishiwaki M., Ishikawa T., Ito T., Shige H., Tomiyasu K., Nakajima K., Kondo K., Hashimoto H., Saitoh K., Manabe M., Miyajima E. and Nakamura H., 1994. Effects of alcohol on lipoprotein lipase, hepatic lipase, cholesteryl ester transfer protein, and lecithin:cholesterol acyltransferase in high-density lipoprotein cholesterol elevation. Atherosclerosis 111: 99–109. doi:10.1016/0021-9150(94)90195-3
  • Nishizawa H., Shimomura I., Kishida K., Maeda N., Kuriyama H., Nagaretani H., Matsuda M., Kondo H., Furuyama N., Kihara S., Nakamura T., Tochino Y., Funahashi T. and Matsuzawa Y., 2002. Androgens decrease plasma adiponectin, an insulin-sensitizing adipocyte-derived protein. Diabetes 51: 2734–2741. doi:10.2337/diabetes.51.9.2734
  • Noll C., Hamelet J., Matulewicz E., Paul J.L., Delabar J.M. and Janel N., 2009. Effects of red wine polyphenolic compounds on paraoxonase-1 and lectin-like oxidized low-density lipoprotein receptor-1 in hyperhomocysteinemic mice. J Nutr Biochem 20: 586–596. doi:10.1016/j.jnutbio.2008.06.002
  • Novakovic A., Gojkovic-Bukarica L., Peric M., Nezic D., Djukanovic B., Markovic-Lipkovski J. and Heinle H., 2006. The mechanism of endothelium-independent relaxation induced by the wine polyphenol resveratrol in human internal mammary artery. J Pharmacol Sci 101: 85–90. doi:10.1254/jphs.FP0050863
  • Pace-Asciak C.R., Hahn S., Diamandis E.P., Soleas G. and Goldberg D.M., 1995. The red wine phenolics trans-resveratrol and quercetin block human platelet aggregation and eicosanoid synthesis: implications for protection against coronary heart disease. Clin Chim Acta 235: 207–219. doi:10.1016/0009-8981(95)06045-1
  • Perissinotto E., Buja A., Maggi S., Enzi G., Manzato E., Scafato E., Mastrangelo G., Frigo AC., Coin A., Crepaldi G., Sergi G. and ILSA Working Group., 2010. Alcohol consumption and cardiovascular risk factors in older lifelong wine drinkers: the Italian Longitudinal Study on Aging. Nutr Metab Cardiovasc Dis 20: 647–655. doi:10.1016/j.numecd.2009.05.014
  • Pinzani P., Petruzzi E., Magnolfi S.U., Malentacchi F., de Siena G., Petruzzi I., Motta M., Malaguarnera M., Marchionni N. and Pazzagli M., 2010. Red or white wine assumption and serum antioxidant capacity. Arch Gerontol Geriatr 51: e72–e74. doi:10.1016/j.archger.2009.12.007
  • Pischon T., Girman C.J., Hotamisligil G.S., Rifai N., Hu F.B. and Rimm E.B., 2004. Plasma adiponectin levels and risk of myocardial infarction in men. JAMA 291: 1730–1737. doi:10.1001/jama.291.14.1730
  • Plauth A., Geikowski A., Cichon S., Wowro S.J., Liedgens L., Rousseau M., Weidner C., Fuhr L., Kliem M., Jenkins G., Lotito S., Wainwright LJ. and Sauer S., 2016. Hormetic shifting of redox environment by pro-oxidative resveratrol protects cells against stress. Free Radic Biol Med 99: 608–622. doi:10.1016/j.freeradbiomed.2016.08.006
  • Polette A., Lemaitre D., Lagarde M. and Véricel E., 1996. N-3 fatty acid-induced lipid peroxidation in human platelets is prevented by catechins. Thromb Haemost 75: 945–949.
  • Renaud S., de Lorgeril M., 1992. Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet 339: 1523–1526. doi:10.1016/0140-6736(92)91277-F
  • Renaud S.C., Beswick AD., Fehily AM., Sharp D.S. and Elwood P.C., 1992. Alcohol and platelet aggregation: the Caerphilly Prospective Heart Disease Study. Am J Clin Nutr 55: 1012–1017. doi:10.1093/ajcn/55.5.1012
  • Renaud S.C., Guéguen R., Schenker J., d’Houtaud A., 1998. Alcohol and mortality in middle aged men from Eastern France. Epidemiology 9: 184–188. doi:10.1097/00001648-199803000-00014
  • Renaud S.C., Guéguen R., Siest G., Salamon R., 1999. Wine, beer, and mortality in middle-aged men from eastern France. Arch Intern Med 159: 1865–1870. doi:10.1001/archinte.159.16.1865
  • Rimm E.B., Klatsky A., Grobbee D., Stampfer M.J., 1996. Review of moderate alcohol consumption and reduced risk of coronary heart disease: is the effect due to beer, wine, or spirits? BMJ 312: 731–736. doi:10.1136/bmj.312.7033.731
  • Rinaldi S., Peeters P.H., Bezemer I.D., Dossus L., Biessy C., Sacerdote C., Berrino F., Panico S., Palli D., Tumino R., Khaw K.T., Bingham S., Allen N.E., Key T., Jensen M.K., Overvad K., Olsen A., Tjonneland A., Amiano P., Ardanaz E., Agudo A., Martinez-Garcia C., Quiros J.R., Tormo M.J., Nagel G., Linseisen J., Boeing H., Schulz M., Grobbee D.E., Bueno-de-Mesquita HB., Koliva M., Kyriazi G., Thrichopoulou A., Boutron-Ruault MC., Clavel-Chapelon F., Ferrari P., Slimani N., Saracci R., Riboli E., Kaaks R., 2006. Relationship of alcohol intake and sex steroid concentrations in blood in pre- and post-menopausal women: the European Prospective Investigation into Cancer and Nutrition. Cancer Causes Control 17: 1033–1043. doi:10.1007/s10552-006-0041-7
  • Roerecke M. and Rehm J., 2014. Alcohol consumption, drinking patterns, and ischemic heart disease: a narrative review of meta-analyses and a systematic review and meta-analysis of the impact of heavy drinking occasions on risk for moderate drinkers. BMC Med 12: 182. doi:10.1186/s12916-014-0182-6
  • Rosenblat M. and Aviram M., 2009. Paraoxonases role in the prevention of cardiovascular diseases. BioFactors 35: 98–104. doi:10.1002/biof.16
  • Rotondo S. and de Gaetano G., 2000. Protection from cardiovascular disease by wine and its derived products: epidemiological evidence and biological mechanisms. World Rev Nutr Diet 87: 90–113. doi:10.1159/000059720
  • Ruf JC., 2004. Alcohol, wine and platelet function. Biol Res 37: 209–215. doi:10.4067/S0716-97602004000200006
  • Ruf J.C., Berger J.L. and Renaud S., 1995. Platelet rebound effect of alcohol withdrawal and wine drinking in rats. Relation to tannins and lipid peroxidation. Arterioscler Thromb Vasc Biol 15: 140–144. doi:10.1161/01.ATV.15.1.140
  • Sacanella E., Vázquez-Agell M., Mena M.P., Antúnez E., Fernández-Solá J., Nicolás J.M., Lamuela-Raventós R.M., Ros E. and Estruch R., 2007. Down-regulation of adhesion molecules and other inflammatory biomarkers after moderate wine consumption in healthy women: a randomized trial. Am J Clin Nutr 86: 1463–1469. doi:10.1093/ajcn/86.5.1463
  • Sarr M., Chataigneau M., Martins S., Schott C., E.l Bedoui J., Oak M.H., Muller B., Chataigneau T. and Schini-Kerth V.B., 2006. Red wine polyphenols prevent angiotensin II-induced hypertension and endothelial dysfunction in rats: role of NADPH oxidase. Cardiovasc Res 71: 794–802. doi:10.1016/j.cardiores.2006.05.022
  • Shaper A.G., Wannamethee G. and Walker M., 1988. Alcohol and mortality in British men: explaining the U-shaped curve. Lancet 332: 1267–1273. doi:10.1016/S0140-6736(88)92890-5
  • Shen Y., Ward N.C., Hodgson J.M., Puddey IB., Wang Y., Zhang D., Maghzal GJ., Stocker R. and Croft KD., 2013. Dietary quercetin attenuates oxidant-induced endothelial dysfunction and atherosclerosis in apolipoprotein E knockout mice fed a high-fat diet: a critical role for heme oxygenase-1. Free Radic Biol Med 65: 908–915. doi:10.1016/j.freeradbiomed.2013.08.185
  • Sierksma A., Patel H., Ouchi N., Kihara S., Funahashi T., Heine R.J., Grobbee D.E., Kluft C. and Hendriks H.F., 2004. Effect of moderate alcohol consumption on adiponectin, tumor necrosis factor-alpha, and insulin sensitivity. Diabetes Care 27: 184–189. doi:10.2337/diacare.27.1.184
  • Soulat T., Philippe C., Bal dit Sollier C., Brézillon C., Berge N., Teissedre P.L., Callebert J., Rabot S. and Drouet L., 2006. Wine constituents inhibit thrombosis but not atherogenesis in C57BL/6 apolipoprotein E-deficient mice. Br J Nutr 96: 290–298. doi:10.1079/BJN20061818
  • Spranger J., Kroke A., Mohlig M., Bergmann MM., Ristow M., Boeing H. and Pfeiffer AF., 2003. Adiponectin and protection against type 2 diabetes mellitus. Lancet 361: 226–228. doi:10.1016/S0140-6736(03)12255-6
  • Steinberg D. and Witztum JL., 2002. Is the oxidative modification hypothesis relevant to human atherosclerosis? Do the antioxidant trials conducted to date refute the hypothesis? Circulation 105: 2107–2111. doi:10.1161/01.CIR.0000014762.06201.06
  • Steinhubl S.R., 2008. Why have antioxidants failed in clinical trials? Am J Cardiol 101: S14–S19. doi:10.1016/j.amjcard.2008.02.003
  • Stockley C.S., 2012. Is it merely a myth that alcoholic beverages such as red wine can be cardioprotective? J Sci Food Agric 92: 1815–1821. doi:10.1002/jsfa.5696
  • Sun B., Spranger I., Yang J., Leandro C., Guo L., Canário S., Zhao Y. and Wu C., 2009. Red wine phenolic complexes and their in vitro antioxidant activity. J Agric Food Chem 57: 8623–8627. doi:10.1021/jf901610h
  • Teissedre P.L., Frankel E.N., Waterhouse AL., Peleg H. and German J.B., 1996. Inhibition of in vitro human LDL oxidation by phenolic antioxidants from grapes and wines. J Sci Food Agric 70: 55–61. doi:10.1002/(SICI)1097-0010(199601)70:1<55::AID-JSFA471>3.0.CO;2-X
  • Toth A., Sandor B., Papp J., Rabai M., Botor D., Horvath Z., Kenyeres P., Juricskay I., Toth K. and Czopf L., 2014. Moderate red wine consumption improves hemorheological parameters in healthy volunteers. Clin Hemorheol Microcirc 56: 13–23. doi:10.3233/CH-2012-1640
  • Tsang C., Auger C., Mullen W., Bornet A., Rouanet J.M., Crozier A. and Teissedre P.L., 2005. The absorption, metabolism and excretion of flavan-3-ols and procyanidins following the ingestion of a grape seed extract by rats. Br J Nutr 94: 170–181. doi:10.1079/BJN20051480
  • Ursini F. and Sevanian A., 2002. Postprandial oxidative stress. Biol Chem 383: 599–605. doi:10.1515/BC.2002.062
  • Van Hecke T., Wouters A., Rombouts C., Izzati T., Berardo A., Vossen E., Claeys E., Van Camp J., Raes K., Vanhaecke L., Peeters M., de Vos WH. and de Smet S., 2016. Reducing compounds equivocally influence oxidation during digestion of a high-fat beef product, which promotes cytotoxicity in colorectal carcinoma cell lines. J Agric Food Chem 64: 1600–1609. doi:10.1021/acs.jafc.5b05915
  • Wang Z., Chen Y., Labinskyy N., Hsieh TC., Ungvari Z. and Wu J.M., 2006. Regulation of proliferation and gene expression in cultured human aortic smooth muscle cells by resveratrol and standardized grape extracts. Biochem Biophys Res Commun 346: 367–376. doi:10.1016/j.bbrc.2006.05.156
  • Willcox B.J., Curb J.D. and Rodriguez B.L., 2008. Antioxidants in cardiovascular health and disease: key lessons from epidemiologic studies. Am J Cardiol 101: S75–S86. doi:10.1016/j.amjcard.2008.02.012
  • Williams M.J., Sutherland W.H., Whelan A.P., McCormick M.P. and de Jong S.A., 2004. Acute effect of drinking red and white wines on circulating levels of inflammation-sensitive molecules in men with coronary artery disease. Metabolism 53: 318–323. doi:10.1016/j.metabol.2003.10.012
  • Yang Y., Liu D.C., Wang Q.M., Long Q.Q., Zhao S., Zhang Z., Ma Y., Wang Z.M., Chen LL. and Wang LS., 2016. Alcohol consumption and risk of coronary artery disease: a dose-response meta-analysis of prospective studies. Nutrition 32: 637–644. doi:10.1016/j.nut.2015.11.013

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Authors


Pierre-Louis Teissedre

ORCID iD

Affiliation : Université de Bordeaux, Institut des Sciences de la Vigne et du Vin
Country : France
Biography :

Enologist from the Pharmacy Faculty of Montpellier in 1989 and Doctor of the University Montpellier 1, he was in 1993 and 1994 Doctor associate of the University of California, Davis – USA in the department of Enology and Viticulture. Pierre-Louis TEISSEDRE is Full Professor in the Faculty of Enology of the University Bordeaux Segalen and was Adjunct Director of the UMR 1219 Œnologie INRA (Mixed Research Unit) with the responsability of the Oenopro Group, actually he is directing the applied Chemistry Laboratory of the USC 1366 Oenologie. Pierre-Louis TEISSEDRE is expert in the group of Technology and is the Scientific Secretary of the Commission «Safety and Health» of the International Wines and Vines Organization (OIV).  He is the Director of Oenoviti international network (55 partners) and Head of the National Oenologist Diploma as well as Foreign Office in ISVV. He is specialized in the research field of grapes and wines phenolics compounds : qualitatives, sensorials and physiological, analytical chemistry of grape and wine, wine quality during winemaking and ageing, food safety (contaminants) and  health in the science of enology. He developed a lot of scientific collaborations at industrial and academic levels. He is author of more than 200 publications and communications in international journals with peer reviews and is co-inventor of 11 patents.


Research topics : Physiological effects on Human Health of phenolics and minerals compounds from wines, grapes and fruits, Nutrition and Analytical Chemistry in Enology, Sensorial aspects of tannins, Food Safety.


Teaching topics : Composition and winemaking (Grapes-Wines) - Special Winemaking, Derivates and sub-products of grapes and wines, Analytical chemistry of musts and wines, Food Safety,  Wine and Health , Polyphenols, Wine ageing

pierre-louis.teissedre@u-bordeaux.fr

Creina Stockley

Affiliation : The Australian Wine Research Institute,
Country : Australia


Mladen Boban

Affiliation : Department of Pharmacology - University of Split
Country : Croatia
Biography :

Department of Pharmacology - University of Split, School of Medicine, Soltanska 2 ; 21 000 Split- Croatia


Jean-Claude Ruf

Affiliation : International Organisation of Vine and Wine (OIV)

Country : France
Biography :

International Organisation of Vine and Wine (OIV)
, Scientific coordinator, 18, rue d'Aguesseau, 75008 Paris, France.


Marta Ortiz Alba

Affiliation : Universidad Nacional de Cuyo (Cuyo National University)
Country : Argentina
Biography :

Universidad Nacional de Cuyo (Cuyo National University), Facultad de Ciencias Médicas (School of Medicine), Química Biológica (Biological Chemistry Department); Avenida Libertador 80, Mendoza - Argentina


Philippe Gambert

Affiliation : SFR 100 Santé STIC, Laboratoire de Biochimie Médicale
Country : France
Biography :

SFR 100 Santé STIC, Laboratoire de Biochimie Médicale, Plateau Technique de Biologie, 2 rue Angélique Ducoudray, BP 37013 – 21070 Dijon Cedex –France


Markus Flesh

Affiliation : Allgemeine Innere Medizin / Kardiologie ; Marienkrankenhaus Soest
Country : Germany
Biography :

Allgemeine Innere Medizin / Kardiologie ; Marienkrankenhaus Soest ; Widumgasse 5, 59494 Soest ; Germany