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[This article was originally written 2004-10-21 and posted on behalf of MR]

Khurram wrote:
> MR wrote:
>> the evidence for other positive health
>> outcomes -- most notably, for total mortality -- is now piled up to the
>> point where I'm quite seriously considering a daily glass of red wine.
I started this experimentally yesterday.
> perhaps we should (finally) optimize/tweak its use as a supplement.
Before going too far, I should say that we really don't know nearly enough to do this well. Even the conclusion that wine is better than other alcohol sources is not uniform; we don't know the active component(s) or the mechanism(s) of action with certainty. Further attempts at tweaking are speculation piled upon preliminary conclusions.
With that caveat:
> *Which* red wine -- or combination of dark wines -- will be
> most efficacious for supplemental use? :
>
> - Northern Italian red [Ed.: I meant New York!], for its putatively highest
> resveratrol content (IIRC)?
It does seem likely that resveratrol may be one key component to this effect -- though NB much of the evidence for wine's superior effect is for wine, without qualification for type.
To the extent that one is seeking high-resveratrol wines, one should go for Pinot Noir. Several independent studies (1-4) have reported higher levels in wines of this cultivar origin. Additionally, (7) reviews that "The concentrations of resveratrol in wine from Vitis rotundifolia (muscardina) grape were higher than those present in wine from Vitis vinifera and Vitis labruscana (Concord) grape." Muscadina cultivars include the old standards 'Scuppernong', 'Hunt' and Thomas', 'Carlos', Cowart', 'Noble', 'Alachua', 'Black Beauty', 'Dearing', 'Jumbo' and 'Southland.'
However, the notion that e.g. New York wines are higher does not seem to be supported by the evidence: there may certainly have been specific years where levels were higher, but the same wine from the same winery can vary year to year, and I found no evidence of a specific, consistently-high level from New York. Leroy Creasy of Cornell University, who reported the finding of higher resveratrol in New York wines, none the less allegedly found that the product highest levels was a Pinot Noir from Oregon:
http://www.northwest-wine.com/benton-lane-pinot-noir.html
http://forum.lef.org/?f=39&m=17154&g=21654
http://www.globalpinoy.com/pinoyhealth/ph_nutrition/NU053104.htm
http://www.avalonwine.com/Cole-Danehower-benton-lane-5-03.htm
More on resveratrol in wine from (5):
----
The synthesis of trans-resveratrol in the plants can be induced by microbial infections [ref] and UV radiation [ref -- but cf (6)]. The content of resveratrol in grape determines the natural resistance to the fungus Botrytis cinerea (gray mold) [ref] [among others -MR]. After an infection of a single berry, the resveratrol content in the neighboring berries increases within a short time. The fungus is able to synthesize an enzyme that degrades resveratrol. This results in a low concentration of resveratrol in *heavily* infected plant tissue [From another ref, which I can't identify at the moment, 10% infected grapes have higher res levels than 40% infected -MR]...
-----
More on factors that modulate resveratrol levels in the papers linked at (6). Unless one is REALLY convinced that resveratrol is THE KEY to this & is willing to do some very intense research on local UV levels, processing methods, etc etc, I suggest that this is largely of academic interest; indeed, if one is THAT convinced, one should probably just take a supplement that contains chirally pure trans-resveratrol is AFAIK the only company in the world with this ingredient in any supplement, tho' we have yet to come out with a high-dose, targeted supplement while attempting to organize some important research) and forget about wine.
> - "Organic" red wine, for it's purer, less-toxic chemistry?
I would suggest that this is a good idea. Moreover, (16) specifically reports: "Sample wines (vintage 1997) were taken from six sites in western Switzerland … [and] one sample was taken from wines grown organically and one from a conventionally maintained vineyard. In all but one sample, neighboring vineyards were chosen in order to compensate for differences in soil properties. …. Organic wines showed higher resveratrol contents rather constantly: in 7 cases, resveratrol content in organic wine was higher whereas in 2 cases resveratrol contents were inferior."

It might be thought that this is the result of higher fungal infection in organic wines due to non-application of fungicides. However, as noted above, higher infection does not necessarily wind up leading to higher resveratrol levels. It's at least equally plausible in principle that organic grapes just wind up cranking up production more due to more chronic low-level exposure. This appears to be a general feature of organic produce: they produce higher levels of a variety of bioactive compounds, including especially phenolic antioxidants, as has been reported in other crops (( 8-12); ALLEGEDLY (13, 14), though I'm cribbing these and have not seen an abstract; cf (15)).
Note, also, that if these other bio-actives are (also) important to the health benefits of red wine -- and it's likely that they are -- then this OUGHT to mean that organic wines are healthier on that count, too.
> - One with an optimal (%) alcohol content?
Pardon my ignorance, & please correct me if I'm wrong, but I'm pretty sure that wines contain a fairly standard 11-15% alcohol. IAC, the majority of the Calories are from the alcohol; if you want more, drink more (within the ~3 glasses range). The apparent selective superiority of wines suggests that alcohol is a minor part of the picture re: total mortality (as opposed to cardio health, where it seems to be a v. important factor).
> - One with highest sulphites [sulfites] content?
I doubt it, and IAC I'm personally maxed out for sulfite intake as it is (for those scratching their heads re this, see:

The CR Society Archives and search for "Sulfites"

> Also, as with many supplements, what is the best time(s) to
> "take it"? Empirically, I would assume w/ dinner.
I think that there are a few reasons to favor this regimen. In reviewing the effects of alcohol on cardio health, (17) notes:
----------
In the studies where only one type of drink was significantly associated with reduced risk of coronary heart disease, that drink was usually consumed by much of the population, typically at levels of one or two glasses a day. This pattern of widespread "healthy" drinking is more likely to take place with meals than is heavy or episodic drinking by a small percentage of the population."
-----------
This may just be the result of the fact that people who drink with meals get their alcohol daily and aren't destroying their organs on a binge; OTOH, it may genuinely be related to a real advantage of taking the stuff with a meal. One plausible mechanism could be the "Ursini effect": taking red wine with a meal quite considerably blunts the postprandial surge in lipid hydroperoxides (21). I crib that "Maxwell et al [(18 ) below] found that 10 subjects who drank wine with meals had higher serum antioxidant activity than others who abstained from wine," but "antioxidant capacity" is often physiologically meaningless.
Taking one's alcohol with meals also slows the rate of alcohol's entry into the system. Aside from being (I ASSUME) less toxic (as it gives your system time to detoxify the stuff), it may be that slower metabolism of alcohol will be more beneficial: "A polymorphism in the gene for alcohol dehydrogenase type 3 (ADH3) alters the rate of alcohol metabolism. We investigated the relation among the ADH3 polymorphism, the level of alcohol consumption, and the risk of myocardial infarction in a nested case-control study based on data from the prospective Physicians' Health Study [ie, this actually is a rather sophisticated prospective design, not a classic case-control study -MR]. ... Moderate alcohol consumption was associated with a decreased risk of myocardial infarction in all three genotype groups ...; however, the ADH3 genotype significantly modified this association (P=0.01 for the interaction). ... Among men who were homozygous for the gamma1 [fast rate of ethanol oxidation] allele, those who consumed at least one drink per day had a relative risk of myocardial infarction of 0.62 (95 percent confidence interval, 0.34 to 1.13 [i.e, no clear effect at all -MR]), as compared with the risk among men who consumed less than one drink per week. Men who consumed at least one drink per day and were homozygous for the gamma2 [slow rate of ethanol oxidation] allele had the greatest reduction in risk (relative risk, *0.14*; 95 percent confidence interval, 0.04 to 0.45). Such men also had the highest plasma HDL levels (P for interaction = 0.05)."
Note, however, that I may be totally misinterpreting this: if the slower polymorphism leads to blood alcohol levels remaining higher longer, and if the 'slow-release' effect of a meal results in lower blood alcohol levels as the stuff takes longer to get thru' the liver (giving it plenty of time to detoxify), then the effect might either be negative, or cancel itself out. (19) found that "No single type of beverage conferred additional benefit, nor did consumption with meals." This was, again, limited to heart disease outcomes. However, it did confirm that men who drank every day had a lower risk of heart attack than those who drank once or twice a week.
> Other than allergic reactions to certain compounds in red
> wine,
Which for some folks, NB, include sulfite allergy.
> which food components and/or supplements may wine
> chemistry be incompatible (deleterious) with if combined?
Here are some alcohol-drug interactions:
http://www.niaaa.nih.gov/publications/aa27.htm
I would also suggest that people not take alcohol in a several-hour window of curcumin, as the former enhances fibrinolysis and the latter decreases fibrinogen. CR folks already have enhanced fibrinolysis, and we DO want our little internal micro-tears to heal, etc. Adding to this, our diets are likely usually higher in salicylates due to greater vegetable consumption; antiplatelet plus fibrinlysis-enhancing effects could be additive.
-Beta-carotene potentiates the hepatotoxicity of alcohol. Alcohol also lowers vitamin A levels and its metabolism by various mechanisms, including inhibiting the conversion of beta-carotene to A . There are reasons to think that alcohol may make beta-carotene generate carcinogenic metabolites, perhaps in part thru' inducing A deficiency, but it isn't clear if this really happens or if it is a risk in nonsmokers and people getting lots of other antioxidants in their diet (see (22) on all of this; on cancer, see also (23), which reanalyzes the CARET study which had previously appeared to show an increase in lung cancer among smoking beta-carotene supplementers if they also drank).
-CR animals already show some abnormalities of A metabolism (24, 25). So don't take high-dose BC supps at the same time as alcohol (& indeed, don't take HIGH-DOSE (>10-15000 IU, e.g.) BC supps at all), and don't take large amounts of alcohol period or at the same time as foods high in BC.
-Vitamin C significantly accelerates alcohol clearance (26), so don't take high-dose C at the same time as wine. (Indeed, I don't see the point of routine high-dose C IAC).
-Alcohol should also not be taken within a few hours of bed, to avoid disrupting melatonin and other endocrine signaling.
> Which may it compliment and/or *positively* enhance (not
> talking about flavor!)?
-It's important to get plenty of folic acid (>600 mg) as part of an alcohol-containing quotidian diet. The negative assoc between folate & various cancers (mostly colon & women's reproductive) appears to be almost entirely confined to people who either have genetic risk for same, or who drink too much alcohol (27-31). This is of course absurd overreaction at 1 glass/day, but likely harmless & *might* just save you a nasty early death.
-Alcohol prevents uptake and absorption of riboflavin; take a supplement.
Also remember that some of us are quite painfully slim, so the mg/kg dose is higher in us -- though perhaps not to so much of a degree as an ALer of similar weight, because s/he will have more body fat and thus proportionately less water-containing tissue, so less fluid in which to dissolve the sauce.
All of this said: Walter Willett's group at Harvard, who are not puritans nor Platonic liars, have concluded that "For a 30-year-old man, the increased risk of alcohol-related accidents outweighs the possible heart-related benefits of moderate alcohol consumption."
http://www.hsph.harvard.edu/nutritionsource/alcohol.html
Alcohol: Nutrition Source, Harvard School of Public Health
However, there is only an increased risk of disease if one either over-imbibes or fails to act responsibly when under the influence (driving, running down stairs with no handrails, doing extreme sports, etc).
They also say, "Your overall health and risks for alcohol-associated conditions should factor into the equation. If you are thin, physically active, don't smoke, eat a healthy diet, and have no family history of heart disease, drinking alcohol won't add much to decreasing your risk of CVD."
This is a much more powerful point. It is certainly likely that the risk reductions we see in the epidemiology, being based on 'all things being equal,' exaggerate the benefits that nuts like us will gain from wine, esp if young and esp if the key mechanisms of action are primarily acute, rather than genuinely preventive.
-MR

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