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Should we all be drinking wine?

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the problem is outlined above. Wine appears to have remarkable effects, even profound effects on overall mortality;however as we all know the evidence is mostly observational and may be simply and association.

The likelihood is that wine drank at very moderate levels is EVEN MORE BENEFICIAL then surmised based on several factors and they are:

1. Underreporting

2. Drink sizes tend to be more than what researchers call a drink. This ties in with the above and exaggerates the overall problem

3. Abstainers are often sickly former drinkers.

4. The very negative effects of binge drinking which is problematic because the overall weekly consumption may appear lite to moderate

Edited by mikeccolella
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The evidence is pretty consistent and it applies to all ethanol intake, not just wine. There are a bunch of studies which point that way, here is one:

"In a model controlling only for overall average ethanol consumption, we found that, compared with moderate drinkers who consumed primarily wine, moderate drinkers who consumed primarily other alcoholic beverages had a substantially increased mortality risk. This difference is consistent with prior studies that have reported that wine, compared with other alcoholic beverages, is uniquely predictive of reduced total mortality (Grønbaek et al., 1995, 2000; Klatsky et al., 2003; Renaud et al., 1999; Streppel et al., 2009). However, these prior studies did not adequately control for potential confounding factors, leading to the concern that the apparent unique effects of wine might be explained by factors associated with both level of wine consumption and mortality (Barefoot et al., 2002; McCann et al., 2003; Paschall and Lipton, 2005). Consistent with this concern, we found strong evidence of confounding sociodemographic, behavioral, and health status factors associated with level of wine consumption among moderate drinkers. Moreover, among these moderate drinkers, all of these factors were significantly linked to increased mortality.
More important, we found that these confounding factors played a pivotal role in assessing the apparent effect of wine consumption on mortality among moderate drinkers. When we controlled for sociodemographic, behavioral, and health status factors in addition to overall average ethanol consumption, the initial mortality difference associated with wine consumption among moderate drinkers was no longer significant. This finding is reinforced by the fact that moderate drinkers who consumed both high and low proportions of wine had a mortality advantage compared with abstainers and supports studies that have not found unique mortality effects for wine."


Here is one study trying to explain the mediating mechanisms for the beneficial effects of alchohol:

"In this large prospective study, we observed a J-shaped relation between alcohol consumption and CVD and mortality among women. Furthermore, we estimated that 86.3% of the lower risk of CVD observed in moderate drinkers was explained by alcohol effects on lipids, glucose metabolism, inflammatory/hemostatic factors, and blood pressure. Nearly 20% of the reduced risk of either total or CVD mortality among moderate drinkers was accounted for by these intermediate factors."


I also ran across a rather interesting summary of why ethanol may be protective on Mercola.com, of all places. But it makes sense to me:


Why Ethanol May Protect You From Methanol

An exciting paper that delves into this topic is food scientist Woody Monte’s “Methanol: A chemical Trojan horse as the root of the inscrutable U,” published in the March, 2010 issue of Medical Hypotheses.

In it, he explains that:

Very low levels of ethanol in your bloodstream would substantively prevent all formaldehyde production from dietary methanol anywhere in the body.

Protection from formaldehyde production may account for the yet unexplained dose region of apparent improvement in the U-shaped curve of alcohol consumption.

Epidemiologic studies show moderate consumption of alcohol is associated with a reduced risk of myocardial infarction, dementia, lupus, and other diseases of civilization. 

Low doses of ethanol appear to provide a preventative measure against the causes of diseases of civilization.

Recent studies of individuals who consumed at least one alcoholic drink per day show subjects had an additional 86 percent reduction in risk of myocardial infarction if they were genetically endowed with a genotype of ADH I that was 2.5 times slower to metabolize ethanol than the control. 

These findings were ‘‘consistent with the hypothesis that a slower rate of clearance of alcohol enhances the beneficial effect of moderate alcohol consumption on the risk of cardiovascular disease.””

It is important to understand that the primary treatment for methanol poisoning in the emergency room is to give them ethanol, for the reasons described above.

The ethanol will preferentially be broken down before the methanol.  The methanol then remains unmetabolized, and in its base form it is relatively nontoxic. It’s becomes a problem when your body breaks it down to formaldehyde.

So while your body is breaking down the ethanol it has enough time to breathe out the methanol unchanged in your lungs and excrete it unchanged in your urine."

I also recall that most of the protective effects of alcohol occur before the age of 55-60 and then subside significantly (kind of like the reverse of protein intake).

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While low-dose alcohol may have it's own hormetic benefits,  I have run across a number of  studies that have identified possible unique benefits to  high-polyphenol red wine intake.

For example:

Alcohol and red wine consumption, but not fruit, vegetables, fish or dairy products, are associated with less endothelial dysfunction and less low-grade inflammation: the Hoorn Study  (2018)





Endothelial dysfunction and low-grade inflammation are key phenomena in the pathobiology of cardiovascular disease (CVD). Their dietary modification might explain the observed reduction in CVD that has been associated with a healthy diet rich in fruit, vegetables and fish, low in dairy products and with moderate alcohol and red wine consumption. We investigated the associations between the above food groups and endothelial dysfunction and low-grade inflammation in a population-based cohort of Dutch elderly individuals.


Diet was measured by food frequency questionnaire (n = 801; women = 399; age 68.5 ± 7.2 years). Endothelial dysfunction was determined (1) by combining von Willebrand factor, and soluble intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1, endothelial selectin and thrombomodulin, using Z-scores, into a biomarker score and (2) by flow-mediated vasodilation (FMD), and low-grade inflammation by combining C-reactive protein, serum amyloid A, interleukin 6, interleukin 8, tumour necrosis factor α and sICAM-1 into a biomarker score, with smaller FMD and higher scores representing more dysfunction and inflammation, respectively. We used linear regression analyses to adjust associations for sex, age, energy, glucose metabolism, body mass index, smoking, prior CVD, educational level, physical activity and each of the other food groups.


Moderate [β (95% CI) -0.13 (-0.33; 0.07)] and high [-0.22 (-0.45; -0.003)] alcohol consumption, and red wine [-0.16 (-0.30; -0.01)] consumption, but none of the other food groups, were associated with a lower endothelial dysfunction biomarker score and a greater FMD. The associations for FMD were, however, not statistically significant. Only red wine consumption was associated with a lower low-grade inflammation biomarker score [-0.18 (-0.33; -0.04)].


Alcohol and red wine consumption may favourably influence processes involved in atherothrombosis.



...it is unclear to what extent alcohol itself (i.e. ethanol) or any additional nutrient components such as polyphenols and flavonoids may determine the association between alcohol and endothelial dysfunction and low-grade inflammation [13]. In the present study, the association between alcohol consumption and the endothelial dysfunction biomarker score was attenuated after adjustment for red wine, while the associations between red wine and the endothelial dysfunction and low-grade inflammation biomarker scores did not materially change after adjustment for alcohol consumption. This suggests that red wine itself, rich in polyphenols and flavonoids, determines its association with lower adhesion molecules and inflammatory mediators (i.e. biomarkers) independent of its alcohol content [12], while an association between alcohol and biomarkers that is independent from red wine cannot be excluded.

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Effects of red wine polyphenols and alcohol on glucose metabolism and the lipid profile: a randomized clinical trial.  (2013)
Chiva-Blanch G1, et al.






Epidemiological data suggest that moderate red wine consumption reduces cardiovascular mortality and the incidence of diabetes. However, whether these effects are due to ethanol or to non-alcoholic components of red wine still remains unknown. The aim of the present study was to compare the effects of moderate consumption of red wine, dealcoholized red wine, and gin on glucose metabolism and the lipid profile.


Sixty-seven men at high cardiovascular risk were randomized in a crossover trial. After a run-in period, all received each of red wine (30 g alcohol/d), the equivalent amount of dealcoholized red wine, and gin (30 g alcohol/d) for 4 week periods, in a randomized order. Fasting plasma glucose and insulin, homeostasis model assessment of insulin resistance (HOMA-IR), plasma lipoproteins, apolipoproteins and adipokines were determined at baseline and after each intervention.


Fasting glucose remained constant throughout the study, while mean adjusted plasma insulin and HOMA-IR decreased after red wine and dealcoholized red wine. HDL cholesterol, Apolipoprotein A-I and A-II increased after red wine and gin. Lipoprotein(a) decreased after the red wine intervention.


These results support a beneficial effect of the non-alcoholic fraction of red wine (mainly polyphenols) on insulin resistance, conferring greater protective effects on cardiovascular disease to red wine than other alcoholic beverages.



See discussion on red wine polyphenol extracts and de-alcoholized wine here:



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Personally,  I decided to  drink small amounts of polyphenol-rich, oak-aged red wine.  I happen to really enjoy  it apart from any possible health benefits,  which may not be so great for an already healthy person,  eating a healthy diet, exercising etc.   (Perhaps Mccoy will chime in here.)

Acutissimin A  by Mccoy



More discussion and debate on alcohol/wine here:



Here's a recent review:

Contribution of Red Wine Consumption to Human Health Protection (2018)



3. Alcohol and Wine Consumption and Their Impact on Human Health

The relationship between alcohol and wine consumption and human health effects has been studied by many researchers [40,41,42,43,44,45,46,47,48,49,50,51,52].

Elmadhun et al. [40] carried out an experimental study on pigs. Their findings suggested that, in moderate doses, ethanol directly promotes new vessel growth in nonischemic myocardium. Platisa et al. [41] have investigated the protective effect of a moderate consumption of red wine on the cardiovascular system. In separate experiments, volunteers drank 0.2 L of red wine and 0.2 L of a control alcohol drink (13.5% alcohol). The immediate effect of both drinks was equal and they increased systolic and diastolic blood pressure. However, after ten minutes, all measured data returned to normal. The prolonged effect of wine and the control drink was different as wine decreased blood pressure and reduced the complexity of the heart-interbeat interval and ventricular repolarization interval.

Matsumoto et al. [42] studied the positive effects of moderate alcohol intake on cardiovascular diseases in adult women and men. The results showed that consumption of 0.15 L of wine or 0.33 L of beer or 0.03 L of liquor lowered the risk of ischemic myocardium, cardiomyopathy, and overall mortality.

The study of Toth et al. [43] indicates the importance of a definitive alcohol dose for a positive effect. Using 39 healthy, non-smoking volunteers aged 18 to 40 years (one group drank water, second group drank 0.2 L of red wine each day for three weeks), they demonstrated the favourable hemorheological effects of red wine. After three weeks, red blood cell aggregation decreased in the group drinking the red wine. Red wine consumption increased red blood cell deformability at high shear stress. These results show that moderate red wine consumption has beneficial effects on haematological parameters, which are generators of cardiovascular diseases, especially coronary artery disease. Elmadhun et al. [44] studied the effects of low to moderate alcohol intake on the risk of developing cardiovascular diseases. They developed a clinically relevant animal model (pigs) for chronic myocardial ischemia to investigate the effects of moderate alcohol consumption on the myocardium. The results showed that alcohol consumption regulates apoptosis and promotes cell survival in ischemic and non-ischemic myocardium. Wine was recommended for its optimal amount of ethanol and other substances with cardioprotective effects. A dietary study of 108 patients with carotid atherosclerosis (65% on statin therapy) who did or did not drink red wine daily (0.1 L women, or 0.2 L men) was performed by Droste et al. [45]. The modified diet and physical exercise, as well as a daily glass of red wine, independently improved the LDL/HDL ratio in patients with arteriosclerosis, even for those on statin therapy.

Chu et al. [46] investigated the effects of two alcoholic beverages, red wine (Pinot noir) and vodka, on cardiovascular function in hypercholesterolemic swine. The goal was to improve a perfusion of ischemic myocardium. Daily intake of 0.375 L of wine or 0.1 L of vodka reduced the risk of cardiovascular diseases compared to normal adult swine.

The objective of the study of Yoo et al. [47] was to examine the health perceptions of red and white wine drinkers from Australia and Korea. Consumers prefer red wine, consuming this with an awareness of the health benefits and protection against myocardial infarction, cardiovascular diseases, and hypertension. The cardioprotective effect of moderate alcohol consumption was examined by Djoussé et al. [48]. The participants of this study were women, including both alcohol consumers and non-drinkers. The participants’ cardiovascular mortality and alcohol consumption rates were followed for 12 years. As compared with abstainers, alcohol drinkers, with an intake of 5 to 15 g per day, were associated with a 26% lower risk of cardiovascular disease, 35% lower risk of total mortality, and 51% lower risk of cardiovascular disease mortality, if the alcohol consumption was mostly red wine.

Another study investigated the effects of regular alcohol consumption on the incidence of cardiovascular diseases and all-cause mortality. They studied the aspects of the overall alcohol-drinking pattern, all-cause mortality, and the risk of cancer and cardiovascular disease. The participants were more than 20,000 Mediterranean university graduates, surveyed every two years. The results showed a significantly lower incidence of death and cardiovascular diseases among wine drinkers than among beer or other alcohol drinkers. This outcome was associated with alcohol intake volume (men 20 g/day, women 10 g/day) in combination with polyphenol intake and the healthier lifestyle of wine-drinkers [49].

O′Keefe et al. [50] wanted to clarify the healthy intake of alcohol as heavy alcohol use is an important factor in the occurrence of reversible hypertension, nonischemic cardiomyopathy, atrial fibrillation, and risk of ischemic stroke. This study had 27,000 participants, including both men and women. They specified that regular low- to moderate-dose alcohol intake (0.1 L of wine per day for women and up to 0.2 L of wine per day for men) is associated with a decrease in the risk of adverse cardiovascular outcomes. The most suitable alcohol source seemed to be red wine.

During few last decades, the French paradox has been mentioned quite often. It means that French people have a relatively low incidence of coronary heart disease despite a diet that includes a high amount of saturated fat. Yamagata et al. [51] studied the preventive effects of polyphenols on cardiovascular diseases and their positive effects on the function of the endothelial cells. Observations of 129,000 adults showed a decreased risk of mortality from cardiovascular diseases in wine consumers compared to other alcohol drinkers. Sinkiewicz et al. [52] also reviewed the reason for the French paradox. Here, lower coronary artery disease occurrence was associated with consumption of wine rather than beer and other alcoholic beverages. People drinking three glasses of red wine every day had the lowest risk of cardiac diseases and mortality. Sufficient daily wine intake also decreased high blood pressure and the risk of myocardial infarction in men aged 65 years and older.

The Hispanic paradox is also being examined in the literature, as well as the French paradox. This anomaly was reviewed by Medina-Inojosa et al. [53]. Daily moderate wine consumption was considered the main reason for decreased cardiovascular diseases. A couple of Hispanic groups living in Europe, USA, and South America were observed and data about their lifestyle, foods, and health condition were collected. The results showed a lower occurrence of cardiovascular diseases compared to other non-Hispanic inhabitants.

Vilahur and Badimon [54] reviewed the cardioprotective effects of the Mediterranean diet on coronary artery disease and atherosclerosis. Their review confirmed that long-term, daily red wine consumption of 0.15 L for women and 0.45 L for men reduced inflammation and atherosclerosis, and improved lipid metabolism, antioxidant state, and endothelial function. Cioni et al. [55] compared relationships between life style, especially eating habits, and endothelial function and coronary artery disease. The study population was composed of 95 clinically stable females (47.9%) and males (42.1%) in primary prevention for cardiovascular disease. All participants underwent a medical questionnaire, clinical examination, and peripheral-arterial tonometry. The reactive hyperaemia index values were higher and the risk of endothelial dysfunction and cardiovascular diseases decreased for participants on the Mediterranean diet with moderate wine consumption. Giacosa et al. [56] describes a Mediterranean diet as being effective in cardiovascular prevention and mortality. This study showed that the Mediterranean diet is beneficial to health even among populations outside the Mediterranean basin.

Tognon et al. [57] studied Dutch inhabitants with different eating habits and the related risk of stroke, coronary heart disease, and cardiovascular mortality. The study had 1849 men and women as participants. The group with Mediterranean dietary eating habits was associated with a lower risk of coronary heart disease and cardiovascular mortality, but not of stroke. The group consuming wine for its alcohol intake was inversely associated with total mortality and with cardiovascular and myocardial infarction incidence and mortality. Stricker et al. [58] explored differences in 40,011 men and women in one group with high intakes of fish, high-fibre products, vegetables, and wine, and a second group, with a Western lifestyle (high consumption of French fries, fast food, low-fibre products, and other alcoholic drinks), for the occurrence of coronary heart disease and stroke. After 13 years of follow-up, 1843 coronary heart disease and 588 stroke cases were documented. The first group was associated with a reduced risk of coronary heart disease and stroke, and the second Western group was not related to any outcome.



Edited by Sibiriak
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The above study addresses the issue brought up by Ron wrt aging and alcohol and seems to support Ron’s contention that alcohol loses its benefits in old age. 

In the meantime I will be reviewing the studies posted by Sibirak and whatever else I can dig up looking specifically for more information, if any, that specifies Wines overall impact on mortality in the over 60 population.

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On 8/4/2019 at 2:11 PM, Sibiriak said:

Personally,  I decided to  drink small amounts of polyphenol-rich, oak-aged red wine.  I happen to really enjoy  it apart from any possible health benefits,  which may not be so great for an already healthy person,  eating a healthy diet, exercising etc.   (Perhaps Mccoy will chime in here.)

Right now I'm regularly drinking modest amounts of digestive bitters so I'm trying to avoid wine not to add more alcohol to my daily dose ( ☠️).

One drawback of wine consumption I found is that wherea I live they produce such good-tasting varities that sometimes it was hard not to overindulge. Fruity, fridge-cold wines in the summer were especially tempting... Also, I found that even very small amounts on an emtpy stomach surpassed the hematoencephalic barrier in a very brief time, resulting in a quasi-narcotic effect.

Maybe I'm going to restart next winter, with cellar-temperatures wines and rigorously during meals.

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Here is an interesting study showing the effects of red wine and vodka in pigs:

"... In this study, we demonstrated that both red wine and vodka improve perfusion to ischemic myocardium, but they do so by different mechanisms. Both beverages also decrease myocardial fibrosis in ischemic myocardium, but only red wine increases perfusion during ventricular pacing, improves segmental shortening and microvessel function, and reduces oxidative stress.

Serum alcohol levels in the swine were somewhat lower than we expected considering the body weight of the animals at the time of euthanasia was only 30 to 40 kg. It may simply be that swine metabolize alcohol differently than humans or that swine serum alcohol levels peak at a different time than that which we chose to draw their blood. Fortunately, the serum alcohol levels achieved in the swine in this experiment approximate that of an adult human after one to 2 alcoholic drinks and were sufficient to produce significant effects.

We specifically chose to use a model of hypercholesterolemia and chronic myocardial ischemia in this study because these comorbidities are very likely to be present in the at-risk patient population that might benefit from the cardioprotective effects of alcohol. Like other studies,16 we found that alcohol supplementation was associated with increased serum HDL cholesterol, whereas total cholesterol levels were unaffected. Although some groups, including our own, have shown that high doses of resveratrol decrease total cholesterol and the low-density lipoprotein:HDL ratio,17 we did not see these effects with the low doses of resveratrol present in our red wine. HDL cholesterol transports low-density lipoprotein from the periphery to the liver where it is metabolized; thus, the favorable lipid profile created by alcohol supplementation may play a role in cardioprotection and the prevention of atherosclerosis.

A key finding in this study is that both red wine and vodka significantly increased perfusion in the ischemic territory at rest. Two mechanisms can lead to increased blood flow in the setting of chronic ischemia: neogenesis of vessels or dilation of resistance arterioles. Hypercholesterolemia has been shown to cause endothelial dysfunction, reducing the ability of coronary arterioles to dilate.18 In a previous study, we found that high-dose purified resveratrol reversed this endothelial dysfunction in the ischemic territory of hypercholesterolemic swine related to its antioxidant effects.17 Similarly, despite a manyfold reduction in resveratrol content, red wine in this study significantly decreased oxidative stress and improved endothelium-dependent microvessel relaxation, phenomena that were not seen in vodka-treated swine. The finding that Sirt-1 and the antioxidant transcription factor phospho-FOXO1 were also upregulated only in the wine group suggests that these effects were in fact mediated by resveratrol.

On the other hand, the increased perfusion in the vodka-treated group appears to be related to increased capillary density, mediated by increases in phospho-endothelial nitric oxide synthase, vascular endothelial growth factor, and phospho-mammalian target of rapamycin, all potent mediators of angiogenesis in ischemic myocardium.19,20 Interestingly, alcohol has actually been shown to inhibit mammalian target of rapamycin activity in cultured myocytes,21 but it may act differently in vivo or in the setting of ischemia. Phospho-endothelial nitric oxide synthase and vascular endothelial growth factor were upregulated in the wine-treated group as well but likely did not stimulate neogenesis of capillaries because perfusion was already improved by arteriolar relaxation.

The different mechanisms by which red wine and vodka improve perfusion may also explain why perfusion was only increased in the wine group under ventricular pacing. In the setting of greater oxygen demand, capillaries in the ischemic territory of vodka-treated swine would provide minimal benefit with regard to perfusion because of their small size and fixed number. On the other hand, the improved ability of resistance arterioles to relax in the wine-treated animals likely allows them to adjust for the increased oxygen demand of ventricular pacing and increase blood flow accordingly. Thus, the antioxidant properties of resveratrol-containing red wine provide additional benefit over alcohol alone with regard to myocardial perfusion.

Although wine and vodka supplementation had no effect on global left ventricular function as measured by developed left ventricular pressure and first derivative of left ventricular pressure, there were significant differences in regional function in the ischemic territory. Red wine supplementation improved contractility in the ischemic territory, likely related to the improvements in blood flow discussed previously. Vodka supplementation, however, actually decreased regional contractility in the vertical axis, although myocardial fibrosis in the AAR was decreased compared with controls. Chronic ethanol ingestion has been associated with increased myocardial fibrosis and global contractile dysfunction,22 but the amounts of alcohol given in this study were insufficient to cause cardiomyopathy. It may be that at lower doses, alcohol actually decreases fibrosis in the ischemic territory. Although we did not specifically examine the molecular basis for decreased fibrosis in these animals, this finding likely relates to the increased myocardial perfusion in the ischemic myocardium in these groups. Antioxidants have also been shown to decrease myocardial remodeling and fibrosis after ischemic injury, so this may play a role in the wine treated animals as well, although they did not demonstrate any less fibrosis than the vodka-treated animals. The decreased contractility in the vodka group could be related to some other mechanism that we did not examine such as increased apoptosis.

A number of studies have shown that the cardioprotective effects of alcohol may actually be related to an inhibitory effect on platelet aggregation.23,24 Our results showed no significant difference in platelet aggregation with either red wine or vodka supplementation, although the small numbers of animals assayed led to substantial margins of error. Nonetheless, both red wine and vodka clearly had beneficial effects on myocardial perfusion, fibrosis, and serum lipid profiles with red wine leading to additional improvements in perfusion and regional function due to its antioxidant properties. These findings shed new light on the mechanisms by which moderate alcohol intake might reduce cardiovascular risk. Whether these beneficial effects are also seen in patients remains to be seen."

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50 minutes ago, Sibiriak said:

That pig study, btw,  is noted in the review I linked above:  Contribution of Red Wine Consumption to Human Health Protection (2018)

"Hypercholesterolemic swine"  makes a good epithet!


Oops, didn't catch it.... LOL.

BTW, while most studies are on red wine, here is something on rice wine (I still think that perhaps the largest protective impact is from the alcohol itself, but that other factors found in wine and other drinks contribute as well):

"The beneficial effect of Chinese rice wine on atherosclerosis has been proved, but the exact components that have the cardiovascular protective effect are still unknown. This study aimed to explore the exact ingredients in Chinese rice wine that could inhibit homocysteine (Hcy)-induced vascular smooth muscle cell (VSMC) proliferation and migration. VSMCs were divided into 7 groups: control, Hcy (1 mmol/L), Hcy + oligosaccharide, Hcy + polypeptides, Hcy + polyphenols, Hcy + alcohol, and Hcy + Chinese rice wine. methyl thiazolyl tetrazolium (MTT) assay, Transwell chambers, and wound-healing assay were used to test the proliferation and migratory ability of the VSMCs. Western blot and gelatin zymography were used to investigate the expressions and activities of metal matrix proteinase 2/9 (MMP-2/9) and tissue inhibitor of metalloproteinase 2 (TIMP-2) in VSMCs. Polypeptides and polyphenols in the Chinese rice wine reduced the proliferation and migration ability of the VSMCs. Furthermore, they also decreased the expression and activity of MMP-2/9 but had no obvious impact on the expression of TIMP-2 in each group. This study further confirms that polypeptides and polyphenols in the Chinese rice wine could inhibit Hcy-induced proliferation and migration of VSMCs and maintain the balance between matrix metalloproteinases (MMPs) and TIMPs."

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There has been a lot of focus on the apparent cardioprotective effects of red wine,  with  resveratrol and other  polyphenols, apart from the alcoholic content itself,  being thought to be possible  causal factors.   On the other hand,  concern has been expressed about the association between alcoholic intake, including red wine, and certain forms of cancer.

It's interesting to note in this regard that resveratrol  and  certain other polyphenols have been shown have  hormetic biphasic dose–response relationships in various circumstances.  

In the case of resveratrol, it may be that low doses like those obtained from moderate red wine intake are cardioprotective while at the same time being tumor-promoting.   This of course is highly speculative.


Cellular stress responses, hormetic phytochemicals and vitagenes in aging and longevity (2012)




8.4. A focus on the hormetic role of resveratrol

Due to its remarkably broad range of effects, including mostly antioxidant and anti-inflammatory activities, immunomodulation, chemoprevention, cardiovascular protection and longevity, resveratrol has attracted numerous researchers investigating the hormetic mechanisms underlining its biological responses in cells and organisms [168]. The emerging body of evidence indicates that the wide range of resveratrol induced end-points displayed a biphasic dose response with quantitative features consistent with the hormetic relationship.

Interestingly, many in vitro studies demonstrated the resveratrol ability to hormetically induce and inhibit cell proliferation in numerous human cancer cell lines, at low and high concentrations, respectively. Several cell lines were affected, such as breast [328], [329], [330], [331], [332], [333], [334], [335], prostate [336], [337], [338], [339], leukemia [340], [341], colon [342], [343], uterus [344], and lung [345] tumor cell lines. These results suggest that resveratrol may prevent or enhance tumor development, according to the extent of the dose applied. It is a crucial point of discussion in consideration of both the relevance given to resveratrol potential chemo-preventive effects, to the implications that resveratrol dietary amount may have for human health and the potential therapeutic dose management [168], [334].

Similarly a consistent hormetic biphasic dose–response relationship was detected by Gu et al. [346] for endothelial human cell proliferation, and also for cell migration, as well as cell adherence and eNOS expression/concentration in injured arteries. These in vitro findings were supported also in subsequent in vivo studies with a rat model. Such studies demonstrated that a low dose of resveratrol enhanced the mobilization of endothelial cells, facilitated re-endothelialization, reduced the occurrence of neointimal formation and up-regulated the expression of eNOS following an induced balloon injury. These findings were not only supported in subsequent research of Xia et al. [347] which corroborated the hormetic-like response of resveratrol on endothelial progenitor cell proliferation and cell migration, but further extended other observations by linking these responses to telomerase activity via AKT-dependent mechanisms. As in the case of the endothelial cell parameters measured, the resveratrol-induced alterations in telomerase activity were also indicative of hormetic responses.

Szende et al. [342] demonstrated that resveratrol biphasically affected proliferation with a low-concentration stimulation and a high-concentration inhibition in human endothelial cells. Using bovine aortic endothelial cells (BAECs), In et al. [348] showed that the resveratrol biphasically affected endothelial cell migration. While the authors acknowledged the capacity of resveratrol to induce a biphasic concentration response, they emphasized that their data revealed that high concentrations of resveratrol might have utility as a potent anti-angiogenesis drug. However, at lower concentrations, the response could switch to angiogenic effects.

Resveratrol has anti-inflammatory properties such as shown with the inhibition of COX-1 [300] and COX-2 [349], down-regulation of prostaglandin biosynthesis and suppression of carrageenan-induced paw edema [300], [350]. Since these collective findings suggested a possible effect on immune response, Falchetti et al. [351] explored, in detail, the effects of resveratrol on multiple immune functions of human T-cells in vitro. These included the development of cytokine-producing CD4 + and CD8 + T cells by stimulating peripheral blood mononuclear cells (PBMC) with anti-CD3/antiCD28, specific antigen-induced generation of cytotoxic T lymphocytes and natural killer (NK) activity of peripheral blood mononuclear cells. These authors reported that there was a hormetic-like biphasic dose response for each endpoint assessed. According to Falchetti et al. [351] these findings suggested a regulatory effect of resveratrol on the immune response. Gao et al. [352], [353] revealed that resveratrol inhibited the Con A induced proliferation of the spleen cells but only at high concentrations. At lower concentrations, the proliferative response was significantly increased. These findings generally supported the conclusion that resveratrol has the capacity to suppress or upregulate immune response depending on the concentration.

Interestingly, a 2005 study by Juan et al. [354] provided such a mechanistic insight into how resveratrol affects a hormetic response in human aortic smooth muscle cells (HASMCs). Resveratrol induced HO-1 expression in a manner that conformed to the hormetic dose response, markedly enhancing HO-1 expression at low concentrations whereas at higher concentrations, this response was diminished. Resveratrol induction of the HO-1 gene was mediated via the NF-kB pathway. In fact, two separate NF-kB inhibitors abolished the capacity of resveratrol to induce HO-1 expression and the activity of the HO-1 promoter. Low concentrations of resveratrol enhanced NF-kB-binding activity based upon experiments assessing electrophoretic mobility shifts. At these low concentrations, the resveratrol trans-activated the NF-kB and this activation process enhanced the transmigration of NF-kB into the nucleus, which then led to the modulation of HO-1 gene expression.

It was demonstrated also that resveratrol had chemopreventive effects with respect to several conditions such as cardiovascular disease [355], Alzheimer's disease [304], osteoporosis [356] and gastric ulcers [357]. From a hormetic perspective, in these conditions, low doses of resveratrol were shown to confer protection whereas higher doses showed adverse health effects. However, in relation to digestive disorders, there are contradictory results that identified resveratrol as a beneficial agent at different doses, without detecting any biphasic dose responses [358].

Various parasitic diseases were also hormetically influenced by resveratrol. Animal models showed that elevated doses protected against Leishmaniasis and Trichinella, while low concentrations consistently enhanced their proliferation [359], [360].

Globally viewing, low concentrations of resveratrol can be potentially beneficial or harmful, depending on the endpoint investigated. In this regard, low doses of resveratrol would have the capacity to increase the risk of tumor development of a number of organs and in contrast to be significantly cardio-protective. This type of conflict between beneficial or harmful effects is not uncommon and it is maybe related to the different biological system, tissue and chemical agent investigated.

Resveratrol is probably the most studied molecule of a series of phytochemicals, including sulforaphane, curcumin, fumaric acid and other chemicals (as previously detailed), that, as hormetic paradigmatic cases, may induce adaptive stress response at subtoxic doses while may be toxic to mammalian cells at high concentrations [18]. However, even if the evidence regarding the hormetic dose–response induced by resveratrol is quite strong, the molecular mechanisms underlining this phenomenon, at present, are not fully understood and deserve greater attention in future research. Moreover, future studies should be focused in putting the findings described into a realistic biological framework to determine whether or not these effects are relevant for human health [361].


Resveratrol: A Double-Edged Sword in Health Benefits (2018)



[...]A study carried out by Martins et al. revealed that resveratrol can modulate different pathways at a time, which can result in distinct and even opposite biological effects, depending on its concentration or treatment time defined. The authors documented that, although a dose-dependent resveratrol pro-oxidative effect leads to cells oxidative stress over lesser time exposure, at same dose but with an increase in exposure time, less expressive cytotoxicity was found. This suggest that surviving cells seemed to be more resistant to resveratrol-induced damages, being its effects attenuated over treatment time [114].

Additionally, low resveratrol doses (0.1–1.0 μg/mL) has been documented to enhance cell proliferation, whereas higher doses (10.0–100.0 μg/mL) induces apoptosis (Figure 2) and decreases mitotic activity on human tumors and endothelial cells [122]. Recently, dual resveratrol pattern effects on HT-29 colon cancer cells death and proliferation were observed, where at low concentrations (1 and 10 μmol/L), resveratrol increased cells number, while at higher doses (50 or 100 μmol/L) resveratrol reduced cells number and increased apoptotic or necrotic cells percentage [123].


Also interesting:


[...] All the above highlighted studies show the pivotal role of dose-dependency and aging in resveratrol-induced responses towards health benefits. Also, in another study, aiming to compare resveratrol effects on aging-induced and re-nutrition-induced insulin resistance and its consequences on arterial system, the authors found that resveratrol improved insulin sensitivity in old mice fed standard diet, while did not improve insulin resistance status in old mice receiving high-protein diets. In contrast, resveratrol exhibited deleterious effects by increasing inflammation state and superoxide production and decreasing aortic distensibility. This data demonstrates that resveratrol seemed to be beneficial to malnourished state of physiological aging, whereas when associated with high protein diets in old mice, may increase atherogenesis-associated risk factors by triggering vascular alterations that could represent an additional risk factor for cardiovascular system [138].


Edited by Sibiriak
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This seems to support the theory:

"In the new study, researchers conducted a number of experiments in mice to determine whether the protective effect of resveratrol against atherosclerosis was related to changes in the gut microbiome. They found that resveratrol reduces levels of trimethylamine-N-oxide (TMAO), a known contributor to the development of atherosclerosis. They also found that resveratrol inhibits TMA production by gut bacteria; TMA is necessary for the production of TMAO.

"In our current study, we found that resveratrol can remodel the gut microbiota including increasing the Bacteroidetes-to-Firmicutes ratios, significantly inhibiting the growth of Prevotella, and increasing the relative abundance of Bacteroides, Lactobacillus, Bifidobacterium, and Akkermansia in mice," said Dr. Mi. "Resveratrol reduces TMAO levels by inhibiting the gut microbial TMA formation via remodeling gut microbiota."

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  • 4 months later...

Hi All!

I drink a small amount of high quality red wine twice weekly.  I find one concerning side effect:  a feeling of tiredness.  A lot of water helps neutralize it.

I suspect that alcohol enters the blood directly, and passes the blood/brain barrier, possibly interfering with brain function.

I intend to reduce my minimal intake of red wine.  (And I certainly have no desire to consume any other alcoholic beverage.)

  --  Saul

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  • 2 months later...


one drink a day to live longer! Woman seemed to benefit more from red wine then men? This was a longevity study and it’s association with alcohol consumption. They were careful to prevent confounding, especially not including former drinkers and things associated with alcohol like smoking.  Interestingly men who drank 30 gms or more daily had the greatest likelihood of reaching 90 years. That’s 2 drinks a day. Woman did best with wine and 1 drink max. So the issue of alcohol and drinking in old age is here being addressed and the results look promising for moderate alcohol consumption. A bit surprising considering aging process and ability to handle alcohol 

Edited by Mike41
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If I recall, the protective effects of alcohol disappear as one gets older and those who start drinking after 55 or so don't get the longevity benefits.

Personally, I have reduced my alcohol consumption to social occasions only, so maybe a couple of times a week, usually two glasses of wine, sometimes three.

What I do notice, however, is that when I drink, my Fitbit tracker registers noticeably poorer sleep and elevated resting heart rate, which usually lasts a couple of days. For instance, for the last week or so my resting heart rate has been about 48-49, while after I had two glasses of wine two nights ago, it went to 52 the first night and 50 last night. My sleep quality was also noticeably poorer the night I drank wine. This has been a consistent pattern over the last few years.

Interestingly, pot has no such effects, so I've adjusted my relaxation routine accordingly :)

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4 hours ago, Ron Put said:

If I recall, the protective effects of alcohol disappear as one gets older and those who start drinking after 55 or so don't get the longevity benefits.

Personally, I have reduced my alcohol consumption to social occasions only, so maybe a couple of times a week, usually two glasses of wine, sometimes three.

What I do notice, however, is that when I drink, my Fitbit tracker registers noticeably poorer sleep and elevated resting heart rate, which usually lasts a couple of days. For instance, for the last week or so my resting heart rate has been about 48-49, while after I had two glasses of wine two nights ago, it went to 52 the first night and 50 last night. My sleep quality was also noticeably poorer the night I drank wine. This has been a consistent pattern over the last few years.

Interestingly, pot has no such effects, so I've adjusted my relaxation routine accordingly :)

This reminds me of a post I wanted to make, so off I go now to the "chitchat" board :)

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A friend of mine who quit drinking was a lifelong functional alcoholic. He is 74 and he quit almost two years ago. He does have brain damage causing him to shake when he does fine motor, however other than that he is in good health. He takes no prescriptions except a statin for cholesterol and he is still quite  sharp mentally. He literally drank 12 cans of beer every day. He would start in the morning. If he drove somewhere he would take two beers with him and pop them into the holders and sip them while he drove. He finally quit due to a DUI and the havoc it caused his life. His 12 a day was a baseline so if there was a special occasion he would drink more. I shake my head in wonder at it. I would be dead if I drank like that. Could there be a confounder with alcohol that is simply those who continue to drink into older ages are just tougher and it has nothing to do with the booze?

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7 minutes ago, Mike41 said:

[...]I shake my head in wonder at it. I would be dead if I drank like that. Could there be a confounder with alcohol that is simply those who continue to drink into older ages are just tougher and it has nothing to do with the booze?

That's me - I too when I witness this kind of behavior, feel that I'd be dead long, long, long ago, trying to do a fraction of that kind of drinking. That was the background to my post on fragility in the "Chitchat" section. I do feel it's possible that those who are capable of that kind of drinking are just tougher built - I know I simply couldn't sustain that.

Btw. the same goes for smoking. My friend's grandfather (now dead), smoked all his life, a pack a day, and lived to 98 in pretty good health (except the last 6 months or so), and sharp mentally all the way to the end. True, he didn't make it to a 100, and his wife who did not smoke lived to 104, but she was in worse shape toward the end (dementia). Incidentally both had a terrible diet, especially her.

I know it's all anecdotes, as always, but when you see this kind of thing all around you all the time, it has an impact. Here I am, taking inordinate care with my health, and I might keel over before some of these "anecdotal" folks who drink, smoke and carry on. As usual, genes are a powerful force. Doesn't make me overly fatalistic, but certainly has me leaning toward having that indulgent glass of wine on rare occasions - I'm not usually a stick in the mud at parties, even if I don't drink as heavily as others. Then again, I don't party too often, so there is that. YMMV.

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38 minutes ago, TomBAvoider said:

... Btw. the same goes for smoking. My friend's grandfather (now dead), smoked all his life, a pack a day, and lived to 98 in pretty good health....

Well, genes do make a difference, as well as luck.

But it'd be like arguing that it's better to run across the freeway than use designated crossings, because  Cousin A has been running across the freeway since he was a kid and is still alive, while Aunt B was run over by a drunk driver at a zebra crossing....

Edited by Ron Put
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Oh, no, I would never think any of this kind of substance abuse was healthy in any way shape or form - it's absolutely not. And as far as smoking, I wouldn't touch it with a ten foot pole - never have, never will. This is a completely different ball game compared to the occasional, or even regular but very controlled consumption of f.ex. wine.

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