#1

Like many of you, I’ve been following the recent headlines about alcohol and brain shrinkage. But I’ve also been frustrated with press coverage stating “no amount of alcohol is safe,” etc., when the data actually paints a much more nuanced picture.

Yes, alcohol has negative effects—especially on the brain and gut. But it also has some positive ones.
And red wine truly does appear to be different.

I just shared a new post, where I dive into three recent studies that examined the relationships between different forms of alcohol and MRI findings, organ-specific aging signatures, and long-term health outcomes. I also get into potential mechanisms for the beneficial effects of red wine, largely driven by proanthocyanidins. Note that this is a very different story than the debunked claims around resveratrol.

TL;DR:
• Alcohol accelerates aging in some organs, but not all. It also has beneficial effects on arteries.
• Red wine is associated with significantly slower aging in the arteries, immune system, and even the brain.
• Red wine consumption is also associated with positive health outcomes including healthy aging, cognitive and physical function, mental health, freedom from chronic disease, and survival.
• Polyphenols like proanthocyanidins likely play a key role. Proanthocyanidins, in particular, limit glucose spikes by inhibiting intestinal glucosidases, enhance arterial nitric oxide production, and decrease inflammatory cytokines. All of these effects are clinically significant at levels consumed in red wine.
• Moderation, timing, and context all matter

I realize that older studies have suggested some of the same things, but the large cohorts in these recent studies give me much more confidence in the result. I’d be curious to hear others’ thoughts.

Full post (for those interested):

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#2

I would love it to be true as I like good red wine, but whenever I have it I immediately feel how negatively it affects me on many levels. Even a small amount, like 4 oz, will affect my sleep, retain fluids, give headache, etc.

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#3

Sounds like maybe you are sensitive to the histamine content?

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#4

This is a fair take on wine consumption. The reality is, that we weigh the pros and cons depending on our priorities. It is possible, that judged strictly on physiological grounds, on balance it’s a net health negative. Whatever advantages in polyphenol content and arterial health can be more than duplicated by other means (fruits and vegetables, statins tec.) without the very real disadvantages of alcohol consumption. You yourself have made that point.

At the same time, it is possible that depending on how you consume your light/moderate doses of wine, perhaps in social settings, there may be some very real benefits of stress reduction, psychological benefits of social connection, even psychosomatic impact.

But ultimately, I believe we must look at effect size. It’s likely that light wine drinking or even very light hard liquor consumption would make no measurable difference in healthspan or lifespan. There is a certain amount of elasticity, compensation and adjustment capability within the human physiology in non-lab free living conditions. The same is true of diet, exercise and other lifestyle factors. An occasional slice of cake within the context of a good diet is likely going to make zero difference in health/lifespan. Exercise, same thing, an extra 5lbs on the bar or an extra rep, 100 yards of a jog etc. will also result in zero impact. But, these small indulgences, glass of wine, slice of cake and so on might make a big difference in quality of life, which might have an outsize impact on adherence to a healthy lifestyle. And ultimately, what are we living for - to enjoy life, or grimly hold on to a deluded sense of purity?

This of course must be strictly dose controlled. Small indulgences - not habitual excess drinking, bad diet sedentary behaviors! We are assuming here top notch diet, exercise, medication regimens 95% of the time, with only small indulgencies in the remaining 5%. Because again, there is some give in the body. We see that in studies, where ekeing out the last few percentages at great cost gives us nothing in measurable outcomes. Look at exercise - it takes shockingly little exercise to extract pretty much all health/longevity benefits, and further exertion brings nothing much, at perhaps a steep price in life enjoyment (for the people who don’t enjoy exercise). Even with diet, it looks like if you eat healthy with moderate frequency, you’re as good as the fanatic in outcomes, and possibly happier.

Bottom line, if you enjoy a glass of wine with a meal, a slice of cake with coffee, an extra hour in the gym, a mile shorter jog, whatnot, it makes no difference in the long term health or lifespan, as long as you’re on point most of the time. The body is very resilient. Your genes have a lot to say. Relax, don’t do stupid stuff, but enjoy life. YMMV.

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#5

I like your take here. I’m glad you brought up social connection, which we know to be a hugely positive predictor for health and longevity. Yes, one can socialize very successfully without alcohol, but if a drink helps one open up and enjoy social situations that would otherwise be avoided, this can and should be considered when making the calculation of whether or not the alcohol is a net positive. The same is true for the other negative or positive aspects one experiences with any substance. Those subjective experiences are as real as the physiological ones.

While I do think it is likely that the positive physiological impacts of wine can be replicated with other sources of polyphenols (I take a daily grapeseed supplement and have seen subsequent decreases in PWV), I also think that there is a possibility that the alcohol actually is an important synergistic component of the positive things that wine is doing. Alcohol itself promotes endothelial nitric oxide signaling and is associated with slower aging in arteries. See the below figure from the Goeminne et al organ aging paper. The combination of proanthocyanidins and alcohol may be better than proanthocyanidins alone - I wonder if anyone has tested this in mice.

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#6

The lack of randomized controlled trials for moderate alcohol use undermines any reasonable conclusion on whether abstinence or moderate drinking is better. But studies that do exist would make a case for moderate use. A research report from the following lists them and provides results.

See Barbería-Latasa M, Gea A, Martínez-González MA. Alcohol, Drinking Pattern, and Chronic Disease. Nutrients . 2022; 14(9):1954. https://doi.org/10.3390/nu14091954

4. Existing Randomized Controlled Trials in the Field of Alcohol Intervention

A number of short-term randomized feeding studies, conducted in small numbers of participants, have tested the effects of alcohol on several intermediate mechanisms. They predominantly examined the effects on lipids, inflammation, and glycemia [98], but not on hard clinical endpoints and cannot replace a formal large RCT. Alcohol intake raised the levels of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1. Additionally, alcohol intake increased adiponectin, an adipokine that increases insulin sensitivity and is inversely associated with diabetes risk [98], reduced fasting levels of insulin and glycosylated hemoglobin [99], circulating levels of fibrinogen and prolonged bleeding time, thus affecting platelet function [100]. Other mechanistic findings are related to the effects of alcohol in increasing sex steroid hormones, particularly estrone [101] and dehydroepiandrosterone sulfate [102]. Alcohol exposure (three to four months in women) found important hormonal effects [102,103]. In the EPIC cohort, a formal mediation analysis reported that an alcohol-related hormonal signature (negatively associated with sex-hormone binding globulin and positively with estradiol and testosterone) was associated with increased breast cancer risk [104].

The longest trial to date of alcohol was the CArdiovaSCulAr Diabetes and Ethanol (CASCADE) trial, which lasted two years and included 224 participants with well-controlled type 2 diabetes [105]. All participants were initially alcohol abstainers, and they were randomly assigned 1:1:1 to consume, with dinner, 150 mL of mineral water, white wine, or red wine. Subjects randomized to initiate red wine increased their HDL-C and Apo A1 and reduced their number of components of the metabolic syndrome as compared to the mineral water group. No differences were found in other outcomes (glycemic control, blood pressure, adiposity, liver function, or quality of life). In Italy, a RCT with 131 patients with myocardial infarction and diabetes (Mediterranean-type diet with or without the addition of four daily ounces of red wine in a 1:1 ratio) reported higher levels of HDL for red wine, lower levels of oxidation markers, reductions in several inflammatory biomarkers, lower fasting insulin levels, and improved left ventricular function after one year [106]. Other small RCTs also tested the intermediate effects of alcohol including counseling to reduce intake [107,108,109,110,111,112,113,114,115,116,117,118,119].

Recently, a 6-month RCT in Australia with 140 drinkers (consuming approximately 120 g/week of pure alcohol at baseline) concluded that abstinence from alcohol reduced atrial fibrillation (AF) recurrences among drinkers with previous AF, who were in sinus rhythm at baseline [120]. The steering committee revised the protocol and shortened the follow-up to six months, instead of one year, because they did not find enough participants willing to abstain from alcohol for 12 months. This was the first RCT of alcohol with a clinical endpoint, and patients in the ‘abstinence’ group reduced their alcohol intake from 16.8 ± 7.7 to 2.1 ± 3.7 drinks/week (an 87.5% reduction), with complete abstinence achieved by 61% of participants in the abstinence group. Surprisingly, apart from these 140 drinkers to date, there is no other RCT in a free-living population evaluating the risk of any other major clinical outcome for two alternative advices on alcohol.

I will also remind folks, that alcohol is the original MTOR1 inhibitor. (And MTOR2 inhibitor at higher dose.) See Foster, DA ,"Reduced mortality and moderate alcohol consumption**:** The phospholipase mTOR connection. Cell Cycle. 2010 Apr 1;9(7):1291-4.

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#7

Same, wine and red wine specifically, gives me migraines. Not every time, but enough to make me very wary of it. Apparently it’s the polyphenols in combination with the alcohol that are the problem, so one person’s dose is another poison. I still enjoy a drink from time to time, in the moment, but it literally makes me sick like nothing else, and feels like poison, so…I generally avoid it in day to day life. I drink tea, eat veggies and fruits, dark chocolate, so I think I’m good on polyphenols. I take beet supplements for microvascular health. My calcium CT score came back at 0.

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#8

Me three. I adore red wine, but once Oura showed me what alcohol does to my sleep, I can’t be convinced that it’s not detrimental to my health.

I still have a glass on occasion, but it’s no longer 1-2x per week.

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#9

I notice that those of us complaining about the ill effects of red wine here are women. Interesting. I’m pretty sure estrogen is involved. We women are more prone to headaches and sleep disturbances anyway, and process alcohol less efficiently.

Histamines were mentioned, but I had a chat about this with ChatGPT a while ago, and it’s more complicated than that. I’ll paste here to share.

The idea that red wine causes migraines due to sulfites is common, but it’s actually a red herring for most people. The real culprits are likely polyphenols, particularly when combined with alcohol, which enhances their absorption and biological activity—and, in some cases, their capacity to trigger migraines.

Here’s a breakdown of the likely migraine triggers in red wine:

  1. Flavonoid Polyphenols (e.g. tannins, quercetin, resveratrol)

Tannins are astringent compounds from grape skins, seeds, and oak barrels. They can trigger the release of serotonin, and in some people, fluctuations in serotonin levels (especially drops after a spike) can lead to migraines.

Quercetin, a flavonol found in grape skins, has antioxidant properties but may cause vasodilation, which is a known migraine trigger in sensitive individuals—particularly when combined with alcohol, which also dilates blood vessels.

  1. Alcohol Itself

Alcohol is a vasodilator, and for some, this alone can set off a migraine.

It also leads to dehydration and affects levels of histamine and neurotransmitters (including serotonin and dopamine), all of which can contribute to migraine onset.

Alcohol impairs aldehyde dehydrogenase, especially in some individuals with genetic variants (such as ALDH2 deficiency), leading to a buildup of acetaldehyde, a toxic metabolite that can contribute to hangover headaches and migraines.

  1. Histamine

Red wine contains higher levels of histamine than white wine, produced during fermentation.

Individuals with reduced DAO (diamine oxidase) enzyme activity may not metabolize histamine efficiently, causing flushing, headaches, and migraines.

Alcohol also blocks DAO activity, compounding the problem.

  1. Interaction Effects

This is where it gets interesting and underappreciated:

Polyphenols + alcohol may work synergistically to affect vascular tone, inflammatory pathways, and neurotransmitter levels.

In some studies, quercetin only causes noticeable effects (like lowering blood pressure or modulating nitric oxide) when consumed with alcohol. That dual activation may be why red wine is a bigger trigger than, say, eating grapes or drinking grape juice.

Summary: Why red wine is worse than white wine

Higher polyphenol content (especially from skins)

Higher histamine load

Higher tannin levels

Often aged in oak, adding more phenolics

Alcohol acts as a catalyst, magnifying effects of all of the above

If you’re sensitive to red wine migraines, switching to:

Low-histamine white wines

Younger wines with less barrel aging

Filtered wines (some use special fining agents that reduce tannins)

…can help. Or just take a page from ancient history and water your wine like the Greeks and Romans did.

So again, some might experience benefits from polyphenols, but for others of us, polyphenols mixed with alcohol are a problematic combination.

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#10

Absolutely brilliant, mmeLaura! I think that you are right about estrogen being involved. I can recall a decade when I could no longer drink red wine due to waking up frequently, having to drink water and pee, while having a low grade headache. That was my decade of Pinot Grigio. Fast forward a decade, and I’m now on HRT, and coincidentally retry red wine…bingo, I’m back to my younger tolerance with no issues.

Now, my sleep is still more disturbed than not with any etoh, but I can again enjoy red wine when I want.

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#11

Ethanol (Grain Alcohol) has effects as ethanol, but also has effects as it is metabolised into first mainly acetaldehyde and then acetate.

argues:

Ethanol has complex direct vascular effects, which include basal vasoconstriction as well as potentiation of both endothelium-dependent and -independent vasodilation. None of these effects appear to be mediated by an increase in nitric oxide bioavailability, thus disputing findings from preclinical models.

Acetate has a serious vasodilative effect and people need to be careful to make sure they have enough water, hence the problems particularly with spirits.

Most of the harm is caused by acetaldhyde. Hence accelerating its conversion to acetate (which apart from being vasodilative is generally quite helpful) is a good idea.

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#12

I wish this were the case for me. I’m on HRT but more often than not, alcohol and red wine especially, gives me a massive headache and makes me feel groggy and achy the next day. Not every time though, and sometimes I get the same feeling without any alcohol at all. Sweet mysteries of life! :grinning:

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#13

A friend on Linkedin mentioned recent work from Brian Kennedy and others showing beneficial effects of low level alcohol consumption in mice. Thought I would share a recent review with some interesting hypotheses:

https://www.sciencedirect.com/science/article/abs/pii/S0741832922000751

“In summary, recent studies on the potential benefit of low-dose consumption of alcohol have provided insight into the potential positive effects of acetate in both health span and lifespan in an aging organism. While data from human studies are fraught with complexity, we propose that a potential benefit of mid-to-late life consumption of alcohol is to moderate the decline in acetate levels and corresponding changes to histone acetylation that accompany aging.”

#14

Acetate is good, but has homeostasis at the cellular level whereas citrate has homeostasis in serum. ACLY and ACSS2 are the enzymes.

You can (and I have) of course increase acetate without the risky naked protons by taking something like sodium acetate, but it still has issues with homeostasis.

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#15

Gastric alcohol dehydrogenase, the enzyme that begins the break-down process
> (metabolization) of alcohol in the stomach, is found in significantly higher concentrations in
> men (about 50% more) than in women. This gastric enzyme metabolizes about 15% of the
alcohol consumed. This means that the amount of alcohol making it to a man’s small intestine for further absorption is much less than the amount of alcohol that reaches the small
intestine of a woman. Thus more alcohol makes it to a woman’s small intestine for absorption. This increases a woman’s blood alcohol concentration (BAC) by about 7% over a man
of equal weight, drinking the same amount over the same time span.

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#16

Coincidentally I read this article today - red wine seems to reduce Lp(a) https://www.mdpi.com/2077-0383/13/3/751

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#17

Its an interesting review:

In our review, we observed that relevant body weight loss, a relatively high intake of saturated fatty acids, the consumption of red wine, and intense physical exercise seems to be associated with significantly lower plasma Lp(a) levels. On the contrary, foods rich in trans-unsaturated fatty acids are associated with increased Lp(a) levels. With regard to dietary supplements, coenzyme Q10, L-Carnitine, and flaxseed exert a mild but significant lowering effect on plasma Lp(a).

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#18

A lot of the benefits associated with red wine would appear to apply just as easily to grapes/blue berries, and other polyphenol rich foods. What makes wine better then eating grapes/drinking grape juice?

I think for real benefits you have to go the social route or microbiome route

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#19

You’d have to eat a ton of grapes/berries to get similar levels of polyphenols, but it is possible. Grapeseed extract supplements are probably the best alternative, IMO, but still might not capture the synergy of alcohol+proanthocyanidin that you get from red wine. Alcohol itself has benefits on arterial health and also helps with proanthocyanidin absorption.

FWIW, I have taken a proanthocyanidin supplement (grapeseed extract) for the past ~6 months and seen a nice benefit on my pulse wave velocity, pushing my value to an age-equivalent 5 years below my biological age. Prior to taking the supplement, when I was only drinking a glass of red wine every day, my value was ~3.5 years below my biological age.

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#20

More likely is just sensitive to acetaldehyde, potentially sulfites and tannins.
The “histamine” in food is rarely a problem between diamine oxidase in our intestines and ubiquitous availability of Histamine type 1 and type 2 antagonists.

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