Saturday, May 29, 2010

Does Red Wine Protect the Cardiovascular System?

The 'French paradox' rears its ugly head again. The reasoning goes something like this: French people eat more saturated animal fat than any other affluent nation, and have the second-lowest rate of coronary heart disease (only after Japan, which has a much higher stroke rate than France). French people drink red wine. Therefore, red wine must be protecting them against the artery-clogging yogurt, beef and butter.

The latest study to fall into this myth was published in the AJCN recently (1). Investigators showed that 1/3 bottle of red wine per day for 21 days increased blood flow in forearm vessels of healthy volunteers, which they interpreted as "enhanced vascular endothelial function". The novel finding in this paper is that red wine consumption increases the migration of certain cells into blood vessels that are thought to maintain and repair the vessels. There were no control groups for comparison, neither abstainers nor a group drinking a different type of alcohol.

The investigators then went on to speculate that the various antioxidant polyphenols in red wine, such as the molecule resveratrol, could be involved. This could be true, but there's another possible mechanism here...

Ethanol-- plain old alcohol. You could drink a 40 oz bottle of malt liquor every night and it might do the same thing.

No matter what the source, alcohol consumption is associated with a lower risk of cardiovascular disease out to about 3-4 drinks per day, after which the risk goes back up (2, 3)*. The association is not trivial-- up to a 62% lower risk associated with alcohol use. Controlled trials have shown that alcohol, regardless of the source, increases HDL cholesterol and reduces the tendency to clot (4).

Should we all start downing three drinks a day? Not so fast. Although alcohol does probably decrease heart attack risk, the effect on total mortality is equivocal. That's because it increases the risk of cancers and accidents. Alcohol is a drug, and my opinion is that like all drugs, overall it will not benefit the health of a person with an otherwise good diet and lifestyle. That being said, it's enjoyable, so I have no problem with drinking it in moderation. Just don't think you're doing it for your health.

So does red wine decrease the risk of having a heart attack? Probably, yes, just like malt liquor does. I do think it's interesting to speculate about why alcohol (probably) reduces heart attack risk. Could it be because it relaxes us? I'm going to ponder that over a glass of whiskey...

* The first study is really interesting. For once, I see no evidence of "healthy user bias". Rates of healthy behaviors were virtually identical across quintiles of alcohol intake. This gives me a higher degree of confidence in the results.


SamAbroad said...

This is fantastic news! I shall enjoy my glass of Jameson all the more now that I know I'm not missing out on any mythical benefits of resveratrol. :) said...

I average less than one drink a year, but I did buy some cabernet yesterday. I plan to drink a tiny amount every evening.

Nancy said...

I love the fact you mentioned the bad parts of alcohol. It always seems like that gets glossed over in all the puff pieces that journalists usually do.

praguestepchild said...

I think lowering stress could be a big factor. But that makes me wonder about caffeine having the opposite effect.

Chris Kresser said...


I recently read a study that showed alcohol reduces small LDL by as much as 20%. If so that is one possible mechanism.

John said...

Considering most Americans are unhealthy, perhaps it is simply the blood-thinning effect that helps slightly--and only in their cases.

Barkeater said...

My late Uncle Harl taught me this:

I only drink to aid my health,
my steadiness to improve.
Last night I got so steady,
that I could hardly move.

polyhex said...

Thanks for pointing this out. I've been aware for some time that the effect is caused by any alcohol.

Question: is there not a level of alcohol consumption which reduces all-cause mortality? I recall reading that light drinking results in a reduction of all-cause mortality. (I think a level somewhat less than 1 drink per day.) But I never looked up and read the studies in question.

Chris Kresser said...

Here's the conclusion from the study I mentioned about alcohol and lipid particle size:

Conclusions: Alcohol intake is associated with less total LDL particles, lower levels of small LDL, HDL, and very-low-density lipoprotein particles, and higher levels of large LDL and medium- and large-sized HDL particles in older adults free of prevalent clinical cardiovascular disease.

David L said...

What do you mean when you say alcohol is a drug? Alcohol is fermented carbohydrates, while cheese is fermented milk. Therefore, shouldn't alcohol be considered a food, albeit one with psychoactive side effects?

Stephan Guyenet said...

Hi Chris,

Thanks, I hadn't heard about that.

Hi Polyphex,

That's true, but apparently if you exclude people from the abstainer group who avoid alcohol due to health problems or alcoholism, the effect disappears

Hi David,

Marijuana and peyote are just plants, would you call those drugs?

Anonymous said...


Giving the passing mention of Resveratrol in this post, it got me wondering what your general take is on the supplemental forms out there today (even ones from what might be considered to be high-quality, reputable companies). Many would say that they automatically violate common sense given that you'd have to consume well beyond a realistic quantity of alcohol daily to get a similar dose. As such, I could assume what your feelings on these might be, but I never like to make assumptions, so I figure it was worth asking.

For that matter it would be interesting to get your very general take on many other substances out there derived from food and then touted and sold in supplement form (for example, curcumin seems to be a big one these days).

Clearly sterling health is about far more than taking any special isolated supplement, but I am curious if you see a lot of the stuff out there as of some potential benefit (albeit no miracles) at best and ineffective, sans downside, at worst or if you actually think some of these supplements may be potentially deleterious in ways we may not yet fully appreciate.

Reverting back to the resveratrol example, it's supplemental forms are often promoted as having plenty of potential upside with no downside, which would make it seem like something worth trying if you had the means and already had all of your other lifestyle ducks in a row. However if there's downside that either gets downplayed, ignored, or possibly has yet to come to light, you'd not only be spending money for no good reason, you'd also be actively undercutting your health, even if doing so unwittingly.

Further muddying the waters is the fact that depending upon what sources you regularly consult for information on these fronts, you're bound to find divergent viewpoints, which can leave those of us without significant grounding in traditional diets or current research and methods feeling like we don't know which end is up.

. said...

Dr. Lorgeril has several papers on this issue. He says that moderate etahanol dirnking results in increased n-3 in cardiac patients. Alcohol intake is associated with higher plasma and red blood cell concentrations of marine n-3 FAs. Maybe the polyphenols might exert these effects. Also, there is data showing positive relationships between wine ethanol intake and ferritin and iron in patients. Could alcohol be anti-inflammatory in the context of coronary heart disease?[Author]

chris said...

I think it is plausible that the non-carbohydrate fractions of grapes are healthier than the non-carbohydrate fractions of grain (or of wood extract, or whatever). Though i agree there is not much evidence of this.

Grapes start out with carb in the form of sucrose, while barley contains glucose chains.i would prefer to consume glucose. however, in both beer and wine, the carbohydrates turn into alcohol.

So if you want some dietary variety, it makes sense to consume your fruit via wine, and grain via bread.

Michael said...


I would be happy to join you for some single malt scotch at the upcoming WAPF convention. :-)

Swede said...

What type of malt liquor should I drink?

Olde English
Colt 45

Surely one of those is better than the others.

Jane said...


You will be interested to hear that wine has high levels of copper and manganese. Have a look at this Guardian article:

'Relatively high levels of potentially hazardous metal ions are frequently found in both red and white wines ..'

The Guardian thinks this is very bad. 'The metals that were of most concern were copper and manganese, the scientists said.' French wines are apparently the worst.

Pretty funny if these 'hazardous' metals are actually the component that explains the French paradox. White bread might not be so bad if you eat it with French wine.

gallier2 said...

In an old internet article I would not be able to find again (from Colpo or Groves or even Kendrick, I don't remember), it was stated that one reason alcohol might be useful, is that it enabled to extract (beneficial) compounds from foods that were neither water nor fat soluble and that are normaly wasted and lost by excretion. I don't know how plausible this hypotheses is but I found it was an interesting path, which might be interesting to look at.

kilton said...

Stephan, thank you for this post. The "alcohol is healthy" nonsense has been more and more vocal of late. It's unbelievable how many studies I've seen over the last few years which conclude that "Alcohol consumption may reduce the risk of (x)". The two new ones last week (though certainly not the first for these ailments) were Diabetes and Alzheimer's. Name a common ailment and there's about a 98% chance you'll be able to find a study saying alcohol "may" help prevent it.

In addition to healthy user bias, I think there's a strong researcher bias here. Just about every adult I know drinks on a regular basis, and I'm sure the people conducting these studies are no different. People want alcohol to be heathly to justify their consumption of it. This, in addition to the fact that all of these pro-alcohol studies get attention by making the news, seems to be the perfect self-perpetuating combination.

Anonymous said...

I used to work as a deiner, and it was well known that atherosclerosis was rare in alcoholics. Livers would be a mess, but their aortas were beautiful smooth. It was always a surprise to the pathologists when we'd find significant athero in alcoholic patients.

Anna said...


Forgive my ignorance, but what is a deiner? The only thing I could come up with is a German word for servant, and that didn't quite seem to fit the context of your observation.

Richard A. said...


This is what I found from Wikipedia --

The word Diener is German for servant. In English, it is generally used to describe the person, in the morgue, responsible for handling, moving, and cleaning the corpse (though, at some institutions dieners perform the entire dissection at autopsy). It is derived from the German word Leichendiener, which literally means corpse servant.

3D Face Analysis said...

I think alcohol passes the "traditional test" in the way that olive oil does. Like olive oil, many traditional cultures have been consuming alcohol for thousands of years. So I don't think alcohol is that bad for you.

Anonymous said...


What Richard said. I assisted the pathologists during autopsies, removing the organs and assisting with their dissection.

Stephan Guyenet said...

Hi Michael,

That sounds good to me!

Hi Swede,

Olde English has the most vitamins and minerals... that's why I drank it in college.

Hi Jane,


Hi Kilton9,

I think a number of epidemiologists think the benefits of low-level alcohol consumption are an artifact of the study designs. People who have health conditions or are recovered alcoholics are often abstainers, so it may make the abstainers look less healthy than they would otherwise. I think the cardiovascular effect is difficult to totally explain away using that argument though.

Hi Leniza,

Thanks for that anecdote.

Jane said...


Have you seen this Klevay paper about beer?

'Rats drinking beer lived nearly six times as long' (as those drinking water) 'and had lower plasma cholesterol, less cardiac enlargement, and higher liver copper.'

The effect was not due to the copper content of the beer, but to something that improved copper utilisation. I suspect this is silicon (orthosilicic acid), which is high in beer and known to do this.

Stanley said...

You've been plagiarized! But it's weirder than that. You've been plagiarized by a sophisticated robot who changed enough of your words to prevent the search engines from detecting the plagiarism. Have a look at this before it gets taken down. It's an awesome ad revenue theft strategy. They leverage your popularity to gain a high search position, then sell ads to people who conclude that the damaged article is nonsense, and want to look elsewhere. Here is where you can report it to Google.

Anyhow, my question was regarding the mention of "Japan, which has a much higher stroke rate than France". First of all, is this "rate" measured in "percent of deaths" or "number of deaths per million people per year"? Any theory as to why? Is it just because the Japanese eat so much omega 3 that they can hardly get heart attacks due to arrythmia, so their overhall heart-related death rate is comparatively low, meaning that stroke must have a higher incidence?

I also wonder whether it's because the Japanese have a much higher cholesterol intake than the French, yet a much lower antioxidant intake. (Yes, I realize that large kernel LDL from seafood is theoretically safe, and that antioxidants can in some cases actually accelerate aging. But one has to explain this finding somehow. It really might be due to accelerated LDL oxidation in the the Japanese, relative to the French. Hopefully you or someone here has a much more cogent theory.)

In all seriousness, I also wonder whether the higher stroke rate has to do with the Japanese tendency to sustain high levels of bloodflow to the prefrontal cortex, as a result of intense and sustained cognition. (I wonder if the majority of these strokes occur in their overloaded left hemispheres. Hmm...)

Stroke rate notwithstanding, Wolfram Alpha says that the Japanese are expected to live to 82, as opposed to 81 in France, but I don't have good data on median age at death (as opposed to hocus-pocus "life expectancy").

Stephan Guyenet said...

Hi Jane,

That's interesting, I hadn't seen it.

Hi Stanley,

Thanks for letting me know. This blog gets ripped off all the time.

The Japanese have a high stroke rate any way you measure it. Stroke in Japan is almost as bad as CHD here. It may be due to the fact that blood pressure tends to be very high in Japan. Some would attribute that to their very high salt intake. I don't know if that's a satisfying explanation or not.

cassan said...

Stephen, you wrote a post a while ago on Hormesis. What if alcohol has hormetic effects in moderation?


Stanley said...


I suspect that you're right about high Japanese blood pressure contributing to stroke. I think their poor amount of sleep and workaholic culture has as much to do with it as sodium. Although, it would be interesting to see if the stroke trend has in any way followed the rise of monosodium glutamate in food, which was patented by their own Ajinomoto corporation in 1909. I couldn't find any public data.

Heath said...

I'm skeptical of the stroke/heart attack rate in Japan. Stroke is considered an honorable death, while heart attacks are not. Who knows what the real rates are...

Mrs. Ed said...

As for the French Paradox, I can't help but think it's not the wine but the cheese. First of all it's from small farms of grass fed cows, then it's not pasturized so it's loaded with beneficial bacteria. I spent a semester in college in France and gorged myself on the cheese. My mysterious autoimmune problems I've had all my life went into remission while I was there (and believe me it's not coincidence, when I came back within days my huge throat ulcers returned). I found out years later I have Celiacs and Crohn's. said...

Very interesting! I used to think that only wine was healthy, and now I can enjoy all spirits with the same enthusiasm! ;)

Berny3 said...

I read sometime in the last year or two (I don't remember where) of a theory some scientists had on how alcohol helps. They were specifically looking at drinking alcohol with dinner. Many people who eat great amounts of carbs in their meals, as most Americans do, get a big spike in their blood sugar an hour or two after eating, many times going over 140, which can cause damage to heart and arteries, even if those people have normal fasting blood sugars and are not considered diabetic or pre-diabetic. The theory goes that alcohol will prevent the big spike in blood sugar, since one of alcohol's effects is to actually lower blood sugar. By the time the effects of alcohol are worn off, the body has been able to process the carbs and deal with them in a less damaging way. Don't know if it's true, but I think it's an interesting theory.

Anonymous said...

I agree with the comment by Mrs. Ed that the high consumption of cheese by the French (cheeseheads)may be a factor in their low rate of heart disease.

Vitamin K2 content of cheese increases tenfold during fermentation. The Rotterdam study showed that increased intake of vitamin K2 greatly reduces CHD mortality and severe aortic calcification. The dominant source (60%)of K2 in the Rotterdam study was cheese. K2 intake in France, mostly from cheese, may well be the highest of all developed countries.

Another factor that contributes to the low CHD mortality in France is the low intake of A1 beta-casein, a protein in milk of cows with a genetic variant that has been implicated in heart disease, type 1 diabetes, and autism. Milk from A1 cows, when digested, can release a peptide of casein called beta-casomorphin-7 (BCM7) that is an opiate, a powerful oxidant and is highly atherogenic. Most cows in the U.S. and northern Europe have A1 genes while cows in southern Europe, including France, produce A2 milk which is similar to the milk of humans and most other mammals and which does not have the problem BCM7 peptide.

The book "Devil in the Milk" by Keith Woodford includes an abundance of evidence that BCM7 from A1 milk causes heart disease, including evidence that A1 beta-casein oxidizes LDL while A2 beta-casein does not, and studies that show that countries that have a high intake of A1 beta-casein also have a high rate of heart disease.

The French have and exceptionally high intake of vitamin k2 and an exceptionally low intake of A1 beta-casein. These factors may largely account for the low CHD mortality in France.

Chris Kresser said...

Yet another factor in the so-called French paradox may be post-prandial stress, which is strongly correlated with heart disease. The French don't have much of that. They have a tendency to eat leisurely meals, and having a glass of red wine along with the meal not only reduces small, dense LDL and blood sugar, it reduces post-prandial stress.

Contrast that with the average American eating an Egg McMuffin in one hand while text messaging with the other and driving with his knees in rush hour traffic.

Neonomide said...

In a recent prospective study in Norway on post-CAD patients, I recall that alcohol beverages on the whole were not beneficial, but red wine was.

Many confounders may explain the association, for example some associated lifestyle factors that seem to follow the red wine consumption. Wine is hardly a drink that many less educated people drink here - they opt for cheaper beer instead.

JLL said...

Bias or no bias, to me the evidence for alcohol lowering all-cause mortality looks pretty strong. And I agree that there is nothing special about red wine, it's the ethanol that is the key.

And if you look at the mortality graphs in other studies, it's not "one glass of red wine per day", it's up to 3 portions per day that is still better than abstaining. More than 3 per day and all-cause mortality gets worse again.


Jeff Z said...

Neonamida, Organism as a Whole, and several others mentioned what I find most intriguing, which is that wine/alcohol is either a sort of catalyst in triggering healthy effects because of the time and place, specifically at a meal, or simply an indicator of a healthier practice, such as people who drink a glass or two of red wine and dinner disproportionally practice healthier habits.

To combine the two, I wonder if it is the drinking all through dinner aspect of wine, as opposed to whiskey, that makes it healthy, not the wine itself. From the opposite angle, perhaps beer, because it is so often consumed at, er, not meal times, shall we see, that may artificially depress its effectiveness.
Along those lines, perhaps the fact that red wine is drank most often with red meat artificially raises its effectiveness?
All speculations of an amateur. I love this site and the comment sections, but just remember what Redd Foxx said, "You don't want to be too healthy...think what a fool you'll look like when you die of nothing."

. said...

"Does wine consumption explain the French paradox?" -

Stephan Guyenet said...

Hi Ricardo,

That's an interesting paper. I just looked at it. The first author makes a convincing case that CHD is under-reported in France, and that the CHD rate is actually similar to other European countries at the same latitude.

But then he claims, based on unpublished data, that the French actually have a modest SFA intake. He appears to have that wrong, as the papers I've seen where they directly measured SFA intake in French cohorts found SFA intakes of 16-18% of calories (compared to about 12-13% in the US at the same time point). I don't know why he cited unpublished data when there are published studies.

Andrew said...

Since coffee and tea can reduce iron absorption, could wine and beer act the same way?

Walter said...

I've always been suspicious of alcohol being good for the heart because it kills brain cells. I don't know of anything else that is good for one organ, but bad for another. Its all one system. Are there examples that I'm just ignorant of?

I'd appreciate your take on this, Stephan.

AngloAmerikan said...

Here's your answer Walter,

..the human brain can only operate as fast as the slowest brain cells. Now, as we know, excessive drinking of alcohol kills brain cells. But naturally, it attacks the slowest and weakest brain cells first. In this way, regular consumption of beer eliminates the weaker brain cells, making the brain a faster and more efficient machine. And that, Norm, is why you always feel smarter after a few beers."Link

Neonomide said...

I tend to bend towards alcohol's effects on post-prandial stress, since France's drinking culture seems to explain some of it. I'd like to know more about drinking culture of similar countries like Greece, Italy and Spain/Portugal.

Similar association may explain why in Western Finland swedish speaking majority drinks at least as much as finnish majority, yet lives longer and gets less CAD. It just does not make sense - finnish people already drink far too much and death rate due to alcohol abuse already is next to Russia in Europe. A more sophisticated eating culture may explain that association nicely. Or critical masculinity theory.^^

Nevertheless, I think Roger Corder may have something to say about the flavonoid theory in his exhaustively referenced book The Wine Diet:

If someone out there wants do do a trial with Madiran, count me in:

I love it's warm and ripe taste. Just bought a bottle only to be sure to get the benefits and the enjoyment at the same time ! ^^

PS: But then chocolate seems to be great stuff for veins - why aren't we hearing more about these in official health talk ?

Neonomide said...

I just have to take an excerpt from that interview above, because this sentence rocks:

"He was attracted to further examination of the Gers region of France because it had double the national average of men aged 90 or above, despite it being the home of foie gras, cassoulet, saucisson and cheese."

Despite potentially antiatherogenic saturated fats and Vitamin K2 content ? ^^

PS: Everyone's favorite cardiologist Dr William Davis loves red wine. Does anyone know on what ground at the moment ?

Jonathan Byron said...

I suggest that anthocyanins (monomers and oligomers) in red wine have a clear effect above and beyond mere ethanol. These have a marked effect on vascular reactivity, collagen stability, insulin sensitivity, and antioxidant status.

Stephan Guyenet said...

Hi Jonathan,

Maybe purified and taken at high doses. But in the context of wine, they apparently have no effect on a number of markers according to a trial published this week.

"Effects of de-alcoholised wines with different polyphenol content on DNA oxidative damage, gene expression of peripheral lymphocytes, and haemorheology: an intervention study in post-menopausal women"

The contribution of food polyphenols to blood antioxidant activity is negligible. Most of them stay in the gut, and those that make it into the bloodstream get filtered out by the liver pronto.

Anonymous said...

The article "The French Paradox: Fact or Fiction" presents compelling evidence that the "paradox" is indeed fiction. Based on the MONICA study, the CHD mortality rate in France is comparable to the mortality rate in other nearby countries. Saturated fat intake in France of about 17% of calories is comparable to other European countries. Furthermore, the assumption that saturated fat is detrimental to heart health that is fundamental to the "paradox" is incorrect.

The Monica study found incidence of deaths from heart disease in in Belfast were three to four times greater than in Toulouse despite all the classical risk studies being "virtually identical". A study by McLachlan (PMID 11425301) found that the intake of A1 beta-casein from milk products was 2.49 times higher in Belfast than in Toulouse. The strong correlation between CHD mortality and intake A1 beta-casein presented in the study provide a realistic explanation for the relatively low CHD mortality of Mediterranean countries.

Anonymous said...

Regarding the preference of the "educated" for wine:

In the Heidelberg study (PMID 18400723) on the correlation between prostate cancer and vitamin K2 intake, 44% of those in the high quartile of K2 intake had a university degree compared to 29% of those in the low K2 intake quartile. The "more educated"(high K2) group also consumed four times more cheese, twice as much dairy products, twice as much fat, 75% more meat, and 60% more calories than the less educated" group.

I suspect that the appetite of the "educated" for wine, cheese, fat, and meat might have more to do with wealth than education.

The intake of alcohol (type not specified) was surprising uniform at 25.5 grams per day across all four quartiles of K2 intake.

The Real Will said...

A doc that I had in the past told me that my HDL was severely low and could result in a massive heart attack. He recommended that I drink a glass of alcohol every day. I asked him if it should be red wine and he said "no, any kind of alcohol will do".

Fast forward, insurance changes, and I am with another doctor now (who is also a cardiologist). I told him about this and he said that I would get the same benefits from drinking grape juice and I told him, no, it's the alcohol. He had me go several months without drinking any alcohol (my choice was red wine) and my HDL droppped, he had me drink wine again for several months and my HDL went back up. He did this several times, and my HDL went up with drinking alcohol, like clockwork. One period I switched to orange juice and vodka (hey, it's got vitmain C, right?, LOL!) and yes my HDL went up, but so did my liver enzymes! :-)

Stephan Guyenet said...

Thanks for the anecdote. I suppose that illustrates the positive and negative side effects of drinking alcohol.

Hendrickus Brokking said...

Thanks for posting this contribution.

Had I pursued - and pursued successfully - that vacancy in Amersfoort some years ago now, I'd have determined to personally congratulate these cautious and reasonably clear-headed medical investigators upon publication of their well-referenced review of the putative beneficial effects both of alcohol per se, and of the other active compounds these complex beverages ordinarily and in vast quantities furnish the imbiber [1].

The ensuing abstract summarizes the review in question. Free full text, incidentally.


[1] Neth J Med. 2008 Dec;66(11):467-73.

Cardiovascular risk is more related to drinking pattern than to the type of alcoholic drinks.
van de Wiel A, de Lange DW.

Department of Internal Medicine, Meander Medical Centre, Amersfoort, the Netherlands.

Many observational studies have shown an association between moderate alcohol consumption and a lower risk for cardiovascular morbidity and mortality. Some of these studies, whether or not inspired by the French paradox, suggest a more favourable effect of wine than of other alcoholic drinks. Certain polyphenols including the flavonoids, more abundant in red than in white wine, are held responsible for this 'bonus' effect. However, this conclusion seems premature, since no significant bioactive effect of wine polyphenols has been shown in humans so far. Furthermore, wine drinking proves to be associated with a healthier lifestyle profile than consumption of beer and liquor, and this may have a substantial influence on the outcome of studies. In contrast to moderate drinking, incidental heavy or binge drinking is associated with an increased cardiovascular risk by influences both on the electrical conduction system of the heart and the process of atherothrombosis. Although only prospective randomised intervention trials including a sufficient number of people will give definite answers, the chances are small that they will ever be performed given the ethical and practical objections of such studies. Available data so far justify the conclusion with regard to cardiovascular risk that the pattern of drinking is of more importance than the content of the bottle.

PMID: 19075312 [PubMed - indexed for MEDLINE]Free Article

Jonathan Byron said...


I don't think that study you cited means anything as broad as what you suggested. It was only one model of anti-oxidant status (a rather unique one, at that). It is also contradicted by a fairly large number of studies that show that anthocyanins are bioavailable and do lead to significant changes in antioxidant status, epithelial function, etc. from the moderate consumption of red wine.

Stephan Guyenet said...

Hi Jonathan,

Would you mind citing some of those studies you mentioned?

Stephan Guyenet said...

By the way, you might be interested in this paper:

Jonathan Byron said...

I've only got a partial list of titles here, but the studies can be found easily enough on Pubmed. Ethanol is the biggest factor in HDL increase, but not in reducing oxidized LDL (which varies with different alcoholic beverages). The vasoreactivity of red wine is greater than other forms of alco-bevs, leading to greater responses (including sometimes migraine, for which red wine is the worst!)

Red wine anthocyanins are rapidly absorbed in humans and affect monocyte chemoattractant protein 1 levels and antioxidant capacity of plasma.

Alcohol-free red wine enhances plasma antioxidant capacity in humans.

Plasma levels of caffeic acid and antioxidant status after red wine intake.

Red wine consumption increases antioxidant status and decreases oxidative stress in the circulation of both young and old humans.

Repeated red wine consumption and changes on plasma antioxidant capacity and endogenous antioxidants.

Dealcoholized red and white wines decrease oxidative stress associated with inflammation in rats.

Muscadine grape products intake, diet and blood constituents of non-diabetic and type 2 diabetic subjects.

Moderate consumption of red wine, but not gin, affects erythrocyte superoxide dismutase activity: A randomised cross-over trial.

The influence of moderate red wine consumption on antioxidant status and indices of oxidative stress associated with CHD in healthy volunteers.

Alcohol: Friend or Foe? Alcoholic Beverage Hormesis for Cataract and Atherosclerosis is Related to Plasma Antioxidant Activity.

Beverage specific alcohol intake in a population-based study: evidence for a positive association between pulmonary function and wine intake.

The role of alcohol in the anti low density lipoprotein oxidation activity of red wine.

Polyphenolic flavonoids inhibit macrophage-mediated oxidation of LDL and attenuate atherogenesis.

Serum antioxidant capacity is increased by consumption of strawberries, spinach, red wine or vitamin C in elderly women.

Effect of red wine consumption on lipoprotein (a) and other risk factors for atherosclerosis.

The effect of ethanol, beer, and wine on histamine release from the dog stomach.

Beer and wine but not whisky and pure ethanol do stimulate release of gastrin in humans.

Vasodilator effects of red wines in subcutaneous small resistance artery of patients with essential hypertension.

Stephan Guyenet said...

Hi Jonathan,

Wine increases plasma antioxidant capacity because it increases uric acid, the primary serum antioxidant. It's not the polyphenols, which are present at negligible concentrations in serum. More later. I'd encourage you to read the paper I linked to previously.

Jay said...

You seem to have completely forgotten the idea of Real/Natural/Whole foods.
In nature alcohol is only found in conjunction with yeast.
Our ancestors were no more likely to find alcohol without yeast than starch without thiamine.
The word "enzyme" literally means "in yeast" and yeast is full of enzymes including ethanol dehydrogenase, so the liver of someone consuming alcohol along with yeast is not called upon to produce its own enzymes.
All commercial alcoholic drinks have nearly all of the yeast removed by racking (settlement) fining (precipitation using fish gelatine or similar) or filtration. This is to prevent spoilage that would occur if all of those enzymes were still present.
However at low temperatures especially below freezing those enzymes are very much inactive.
In the North of Pakistan the climate allows the growimg of grapes in the summer and is cold in winter.
In the Hunza valley they make "Pani" which is fermented grape juice with the yeast left in and the men over 30 years old drink quite a lot over the winter but it goes off soon after the snows melt.
Although virtually no really reliable data comes from this remote place, a Western doctor claimed that liver disease was non-existent in this population.
In 1998 a french group announced that they were going to do research on this subject but I have not seen anything published.

Stephan Guyenet said...

Hi Jonathan,

Thank you for posting those references. I don't dispute the results, but I do have a few problems with the interpretation of these studies. The concentration of polyphenols in human blood after consuming these foods is very low, too low to account for the effect of eating polyphenol-rich foods on serum antioxidant capacity. Here's a quote from the paper I ref'd above:

"Despite the strong antioxidant capacity of flavonoids in vitro,
their antioxidant efficacy in vivo is limited by several factors.
First, the absorption of flavonoids in humans is low, in contrast to other dietary antioxidants such as vitamins C and E. The maximal plasma concentrations of flavonoids in humans, reached usually between 1 and 3 h after consumption of
flavonoid-rich foods, are between 0.06 and 7.6 μM for flavonols, flavanols, and flavanones, and less than 0.15 μM for anthocyanidins (Table 1) (reviewed in [34]). In addition, the
half-lives of flavonoids in human plasma are short, usually in
the range of a few hours. These factors severely limit the
capability of dietary flavonoids to act as antioxidants in plasma
in vivo, especially compared to other antioxidants present in
plasma at high steady-state concentrations, e.g., 30–150 μM
ascorbate (vitamin C), 160–450 μM urate, or 15–40 μM α-tocopherol (vitamin E) [35]. Chronic or long-term consumption of flavonoid-rich foods also does not result in accumulation of significant amounts of flavonoids in plasma.

In addition to being poorly absorbed, flavonoids are extensively metabolized in intestine and liver. Flavonoids are
good substrates and inducers of phase II enzymes [37,38], suggesting that they are recognized by the body as xenobiotic— and thus potentially toxic— compounds, most likely due to their polyhydroxylated structure and potent redox activity."

In other words, even right after consuming a large amount of polyphenol-rich food, the concentration of these compounds is not sufficient to account for the increased antioxidant capacity of serum. So why does it increase? It's probably because these foods increase the level of uric acid in serum. Here's another quote:

"Even when the kinetics of the appearance of flavonoids in plasma and the increase in plasma antioxidant capacity are closely related, the extent of the increase in plasma antioxidant capacity usually far exceeds the plasma concentrations of flavonoids and their metabolites, which are in the nanomolar to low micromolar range (Tables 1 and 4).

Cao et al. [116] found significant increases in plasma urate after consumption of strawberries, spinach, or red wine that corresponded to significant increases in plasma ORAC-PCA, FRAP, and TEAC.

Another study [92] also found an increase in average plasma urate levels of about 40 μM, or 12% from baseline, after the intake of regular or dealcoholized red wine.

Natella and colleagues [133] found significant increases in plasma urate of 18 and 24 μM, or 5 and 7%, 1 h after drinking coffee or green tea, respectively, which was paralleled by increases of 6 and 5% in total antioxidant capacity (Table 4)."

Stephan Guyenet said...

Continued from above...

Etc. Given that uric acid is the main antioxidant in human serum, it's much more plausible that it's responsible for the antioxidant effect, and perhaps the other vascular effects as well, than that polyphenols are the direct cause. Then again, it could be that polyphenols are what's causing the increase in uric acid. Perhaps they increase uric acid excretion by the liver.

Fructose also increases plasma antioxidant capacity by increasing uric acid; this effect is responsible for the increase in plasma antioxidant capacity after eating fruits, which is generally attributed to polyphenols.

The fact that wine increases uric acid is why some doctors will advise that people with gout avoid it.

The other problems of interpretation with these studies is that most of them aren't appropriately controlled to make the conclusion that polyphenols are responsible for the effects they observe. As far as I know, the idea that polyphenols themselves are the active ingredient in red wine extract is an unproven assumption.

A final problem I have is that some of the studies on polyphenols use unrealistically high doses, particularly the animal studies.

Unknown said...

High alcohol consumption AND alcohol abstainers: linked to depression, since they have a less than optimal social network = they die early.

Moderate consumption: moderate drinkers drink in a social context mostly, which strenghtens, or is an indicator of, a good social network = live longer.

I don't think alcoholic beverages prolongs life due to some magic properties etc, you need to look at the context and lifestyle factors associated with it.

Stephan Guyenet said...

Hi Martin,

I think the idea that the benefit comes from psychological/social factors is plausible. There may be clues in the scientific lit. I may try to look into it at some point.

Anonymous said...

Even if it's not the resveratrol I shall continue to drink red wine because I like the flavour.

Small quantities of alcohol do indeed allow me to eat more carbs than I normally would without spiking my BG. Except for beer, more than half a pint and the carb content outruns the alcohol and puts by glucose up. Some diabetics with Dawn Phenomenon (high BG in the morning before eating) find red wine at night (and in one case rum) blocks this rise.

"He was attracted to further examination of the Gers region of France because it had double the national average of men aged 90 or above, despite it being the home of foie gras, cassoulet, saucisson and cheese."

Er, I think that should read *because* of it being the home of . . .

Prepare to see the French Paradoz disappearing soon, I read that the WHO are specifically targetting France with their CINDI diet which will guarantee to destroy the effect.

OTOH there now appears to be an American Paradox caused by the readers of this and similar blogs.

Rainer said...

Hi Trinkwater,

the effekt of alcohol on BG is well known. Red wine or another drink do the same job as metformin, preventing liver from dumping glucose.

May be that this simple thing causes the French Paradoxon - preventing development of a full-fledged diabetes with metformin (
short/346/6/393) or with a daily glass of red or white wine. It taste much more better then metformin.

Anonymous said...

Good point! Also the wine doesn't give you the squits.

Alpha lipoic acid is another thing with a similar effect on the liver, reducing excess glucose generation/release: might be useful for non-alcohol drinkers.

Jonathan Byron said...

Here is a new study that shows that pre-exposure to red wine (but not an equivalent amount of alcohol) protects against the toxic effects of amphetamine:

Please, people - recognize reductionism at work. Red wine cannot be reduced to mere alcohol, any more than a complex food can be reduced to merely grams of protein, fat, and carbs.