Image by Debbie EM from Pixabay

You’ve probably heard heard that wine (or, more specifically, the resveratrol in red wine) is good for the heart. You’ve probably also heard, on the flip side, that in order to get enough resveratrol to do your heart any good as an antioxidant, you’d have to drink truckloads of it (true), at which point it of course becomes toxic to the liver. Plus, alcohol can lead to weight gain, of course (though indirectly—I explain how this works here). Weight gain can lead to insulin resistance, which is a strong risk factor for heart disease… so doesn’t it stand to reason that wine is, in fact, not good for your heart?

And yet, there have been decades’ worth of studies that seem to establish a clear association between moderate wine intake, and decreased cardiovascular risk. How is this possible? 

The J-shaped Curve of Benefit to Harm

Many studies have demonstrated an inverse risk between wine intake and heart attacks—to a point, and then when alcohol intake continues to rise past the point of moderation, risk steeply increases. 

This is the concept of hormesis in action: a small amount of a toxic substance can prove beneficial, but only to a point, after which it becomes a poison. 

This wasn’t the publicized message, though—this author writes the the reason was because, given the addictive potential of alcohol, it’s better to abstain entirely, and forego the initial benefit it might confer. 

The Blue Zone Effect

The parts of the world where people tend to live the longest, healthiest lives are known as the “Blue Zones”. The top 5 best known are Ikaria, Greece; Loma Linda, California; Sardinia, Italy; Okinawa, Japan; and Nicoya, Costa Rica. While diets vary widely between all of these locations, they have many habits in common. One of those habits is moderate wine intake (around one glass per day for women, and two for men). 

Why is this beneficial, if it’s not simply due to the antioxidant capacity of the resveratrol?

What Else Resveratrol Can Do

Resveratrol is one of the darlings of the longevity world, more for its ability to set off a biochemical cascade that ultimately raises NAD+ and sirtuin activity. NAD+ is important for ATP production, improved metabolic efficiency, and it’s required for the anti-aging activity of sirtuin proteins. 

Resveratrol also activates AMP-activated protein kinase (AMPK), which stimulates the mitochondria to produce more ATP while simultaneously conserving the ATP that is already present. AMPK can be stimulated by fasting and intermittent fasting, and suppressed by obesity and overeating. But it’s possible to affect AMPK by nutrients alone, as well. Resveratrol is one of the nutrients that can do so.

Polyphenols generally, of which resveratrol is one, can also inhibit mTOR (mammalian target of rapamycin), which in turn triggers autophagy (the body’s natural “clean-up” process of breaking down cells that aren’t working optimally, so that new ones can take their place). Autophagy is very associated with longevity. While mTOR also goes up with specifically protein intake, and down with fasting, polyphenols, such as resveratrol, can lower mTOR as well.

Quercetin in Wine

Another polyphenol in red wine is quercetin. The same mTOR-suppressing benefits apply to quercetin as to resveratrol. 

Quercetin has also been shown to potentially inhibit clot formation in animal models. Since clotting is arguably the primary mechanism of atherosclerosis, this is particularly relevant from a cardiovascular standpoint. 

Along those lines, other unspecified bioactive compounds in wine may reduce platelet-activating factor, which would also decrease risk of clotting. 

More Than The Sum Of Its Parts?

But it’s also possible that the health benefits of wine as a whole are greater than the sum of its parts. We can isolate a few of the constituents of wine and test their effects individually, but there may be many more that we haven’t yet discovered, or it may be due to a synergy between them. 

Could the fermentation have something to do with the benefits too? 

Could it be the interaction between multiple types of polyphenols from an antioxidant standpoint, rather than one alone, as they are always stronger together? 

Perhaps the fact that wine stimulates the GABA receptors, which aids in stress relief, plays an important role.

The Upshot

The main takeaway here is of course moderation. While small amounts of wine seem to be beneficial not only for cardiovascular, but for all cause mortality, risk ascends steeply upwards of two glasses per day. Studies vary somewhat on optimal amounts, but this generally seems to be the upper limit. I prefer to keep my patients well under this amount, due to concerns of B vitamin and glutathione depletion from liver processing, as well as concerns of weight gain. And of course, anyone with a history of substance abuse should probably abstain altogether. 

As this author pointed out, though, the positive side of wine intake (and it is substantial) has been suppressed due to concerns of potential excess—already such a problem in our society. As usual, the happy medium lies somewhere in between.