Page last updated: September 24, 2012
Red wine and the protective effects of polyphenolics

Presentations from the European Society of Cardiology Congress in August 2012
Francesco Sofi from the University of Florence, Italy told attendees that there is a way to enjoy food and enjoy too the benefits of protection against CVD and even mortality risk. “You can eat well and live a long time,” said Sofi, provided that what you eat is predominantly a Mediterranean diet.
A 2010 meta-analysis performed by Sofi and colleagues - which comprised a total study population of more than 2 million subjects - confirmed the significant and consistent protection provided by adherence to the Mediterranean diet against the major chronic degenerative diseases and death. This was seen as a 10% significant protection against overall mortality (RR 0.92) and cardiovascular incidence or mortality (RR 0.90) - even from a slight increase in adherence to a Mediterranean diet.
The diet, explained Sofi, refers to a dietary menu commonly available in the early 1960s in the Mediterranean regions (though perhaps less so today) and characterised by a high consumption of fruit, vegetables, legumes and complex carbohydrates, with a moderate consumption of fish, olive oil as the main source of fats, and a low-to-moderate amount of red wine during meals.
. . . but is red wine as protective as suggested?
While red wine is central to the Mediterranean diet, it remains a subject of ever increasing mystery to Eric Sijbrands of Erasmus University Medical Center in Rotterdam. Certainly, he says, epidemiological studies appear to confirm a cardioprotective effect, but the mechanism by which that protection is delivered seems increasingly unclear.
The favoured theory has been an effect of the polyphenol resveratrol, found in the skin of red grapes and lately invested with all kinds of life-giving properties. Small studies have suggested a beneficial effect of red wine on lipid metabolism, which, says Sijbrands, “still stands”, and an effect on vascular function mediated through endothelial cell function (as an anti-oxidant effect). But Sijbrands is doubtful whether any of these effects can be justly attributed to a single polyphenol such as resveratrol. He thinks it is likely that the explanation for red wine’s apparent cardiovascular benefits will be complex.
The reasoning behind the resveratrol theories largely dates back to explaining the “French paradox”, raised by St Leger et al in the Lancet in 1979 by which the French, with a high consumption of saturated fat, also had lower mortality rates from CHD than other countries with similar fat consumption. St Leger’s principal finding was a strong and negative association between CHD mortality and alcohol consumption, particularly red wine.
Resveratrol has been studied and promoted as that constituent, but studies performed by Sijbrands’ group in Rotterdam have failed to replicate results from any of them. For example, a study reported this year found that intake of red wine polyphenols in two dosages for four weeks did not decrease peripheral or central blood pressure in subjects with hypertension.
Yet the epidemiology, dating to back to St Leger in 1979, suggests that red wine, especially if taken in moderation and with food, does confer some benefit in some people. But, says Sijbrands, the emphasis on moderation is justly made, for whatever the benefit, it is likely to be only small, and far less than the adverse effects derived from excess.
Dietary (Poly)phenolics in Human Health: Structures, Bioavailability, and Evidence of Protective Effects Against Chronic Diseases. Antioxid Redox Signal, 17 Aug 2012.
In this paper, authors Daniele Del Rio, Ana Rodriguez-Mateos, Jeremy P.E. Spencer, Massimiliano Tognolini, Gina Borges, and Alan Crozier provide a comprehensive review which describes the different groups of compounds that have been reported to be involved in human nutrition, their fate in the body as they pass through the gastrointestinal tract and are absorbed into the circulatory system, the evidence of their impact on human chronic diseases, and the possible mechanisms of action through which (poly)phenol metabolites and catabolites may exert these protective actions.
They concluded that better performed in vivo intervention and in vitro mechanistic studies are needed to fully understand how these molecules interact with human physiological and pathological processes.
The  paper states that although trans-Resveratrol is widely credited with being responsible for the protective effects of red wine in both the press and the scientific literature., this is almost certainly not true, as the level of the stilbenes in red wines is so low that > 60 liters would have to be consumed on a daily basis by humans for intake to reach the amounts that are required to increase longevity and provide protective effects in model animal systems. Resveratrol is an extremely minor component in the human diet, and as such, its potential use is as a therapeutic agent at pharmacological doses.
Specifically  for Red wine, the paper states that “it is well accepted that excessive alcohol consumption leads to increased BP in normotensive and  hypertensive subjects, whereas low/moderate consumption reduces specific cardiovascular risk factors. Reports regarding the effects of red wine and red wine (poly)phenols on BP are in most case inconsistent. While there is extensive evidence to support the influence of wine intake on cardiovascular health, controversy remains whether red wine in particular exerts beneficial effects compared with other alcoholic beverages or simply alleviates the detrimental influence of alcohol on BP. In acute studies with healthy volunteers, no changes in BP were observed, but an increase in the heart rate was reported after red wine consumption whereas in CAD patients, a decrease in systolic and diastolic BP was noted together with an increase in heart rate, 1 h post wine (red and white). Other studies have reported no changes in hemodynamics or BP after medium-term daily intake of either red wine or its dealcoholised equivalent. However, in the majority of these studies, no proper control was used.
Several studies report the effect of red wine and/or its dealcoholised equivalent on endothelial function, although again, there is inconsistency in the findings. For example, some studies indicate that dealcoholised wine, but not red wine, induces an increase in Flow-mediated dilation (FMD); others suggest the opposite; and another suggests that both red wine and dealcoholised red wine are equally effective. Other studies have shown no effect, or even a decrease, in FMD after red wine or alcohol consumption. The reason for these inconsistencies may be the increase in the baseline brachial artery diameter due to alcohol reported in all the studies, which will affect FMD responses, as pointed out by Spaak et al. With regard to longer-term (2 weeks to 2 months) red wine consumption, the majority of studies suggest that there is no significant effect on FMD or arterial stiffness.
In addition to BP and endothelial function, several studies  have also reported that regular medium-term intake of red wine (2–12 weeks) may increase HDL-C and lower LDL-C As there were no controls used in these studies with alcohol, it remains unclear as to whether the alcohol itself, rather than (poly)phenols, was responsible for the favorable effects of red wine. Indeed, HDL-C has been found to increase after a 28-day intake of either red wine or gin.
Acute studies have failed to show a positive effect on platelet function after red wine consumption. However, red wine, dealcoholised red wine, white wine, and alcohol all appear to have the same beneficial effects on platelet function after 4 weeks of intake which suggests that the positive effects of moderate consumption of wines on platelet function seem to be due to their alcohol content.
Resveratrol a stilbene found in grape seed, has been postulated to be partly responsible for the beneficial vascular effects of red wine. Indeed, 30, 90, or 290mg of transresveratrol has been shown to improve endothelial function in overweight subjects in a dose-dependent manner and animal studies support this, as resveratrol reportedly improves survival rates, endothelium-dependent smooth muscle relaxation, cardiac contractile, and mitochondrial function in a hypertensive model of heart failure. However, while the conjecture that resveratrol may underpin the vasoactive effects of wine seems logical, the majority of red wines actually contain very little of the stilbenes, and thus it is unlikely that it is responsible for the beneficial effects of red wine in vivo’.

Wine, beer, alcohol and polyphenols on cardiovascular disease and cancer. Arranz S, Chiva-Blanch G, Valderas-Martínez P, Medina-Remón A, Lamuela-Raventós RM, Estruch R. Nutrients. 2012 Jul;4(7):759-81. Epub 2012 Jul 10.
A review from Barcelona University summarises the main protective effects on the cardiovascular system and cancer resulting from moderate wine and beer intake due mainly to their common components, alcohol and polyphenols.
The authors conclude that  ‘Sufficient evidence supports a significant inverse association between regular and moderate wine consumption and vascular risk, particularly red wine, and a similar relationship is reported for beer consumption, while lower protection is described for the consumption of any spirituous beverage.
Clinical and epidemiological studies indicate that it is mainly red wine which may protect against CVD, atherosclerosis, hypertension, certain types of cancer, type 2 diabetes, neurological disorders and metabolic syndrome.
There is evidence that certain polyphenols, such as resveratrol, anthocyanins, flavonols and catechins in wine provide an abundance of health benefits. Furthermore, rather than polyphenols themselves, their metabolites might be the real key players in cardiovascular and cancer protection. In beer, xanthohumol and its metabolites isoxanthohumol and phytoestrogen 8-prenylnaringenin also provide healthy properties such as anticarcinogenic, anti-invasive, anti-angiogenic, anti-inflammatory and antioxidant effects. The complexity increases when considering that each subject may metabolize the beverage differently, making it impossible to establish one specific constituent as being critical from a health standpoint.
It must be emphasized that the benefits associated with red wine and beer are dependent upon regular and moderate consumption. Although general recommendations are one drink (150 mL of wine or 10 g of alcohol) daily for women and two drinks (300 mL of wine or 20 g of alcohol) daily for men, individual ideals may vary based on age, gender, genetics, body type and drug/supplement use. These different recommended daily doses of alcohol between genders are explained by the fact that women are more sensitive to the effects of alcohol on the body. In addition, any healthy effects of wine and beer are greater in combination with a healthy diet. The health benefits associated with the Mediterranean diet, which combines moderate wine and beer consumption with a diet rich in fruits, vegetables and whole grains, suggests that polyphenols have synergistic effects with compounds found in other groups of foods.
Although alcohol consumption is a two-sided coin, moderate alcohol consumption especially of wine has demonstrated the provision of a protective role for the cardiovascular system and in some types of cancer. Most medical professionals as well as the American Heart Association agree that heavy drinkers or alcohol abstainers should not be encouraged to drink wine for health reasons. Wine consumption should not replace a healthy lifestyle. However, light-to-moderate wine drinkers, without medical complications, may be assured that their wine consumption is a healthy habit.
Nevertheless, more randomized clinical trials focused on elucidating the mechanisms of the action of alcohol and polyphenols are needed’.

For the full critique of this paper by members of the International Scientific Forum on Alcohol Research please click here.
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