Resveratrol Instead of Aspirin for Heart Health

Resveratrol Can Stir Your Blood

Resveratrol Instead of
Aspirin for Heart Health

The remarkable red-wine compound inhibits
clot formation in the blood of aspirin-resistant patients
By Will Block

n weaving their beautiful rugs, the Navajo Indians deliberately insert small errors into the otherwise perfect symmetry of their designs. They do this so as not to offend the Great Spirit by presuming to have created something perfect. Even in nature’s own creations, however, perfection of form is elusive, no matter how refined the underlying design. Indeed, some natural objects of great beauty—pearls, for example—can arise only through an imperfection of some kind.

For a pearl to form inside a mollusk, the imperfection must be some irritant, such as a wayward food particle (a grain of sand rarely works). The mollusk responds to the irritant by encasing it in a layer of material called nacre, or mother-of-pearl, and voilà—a pearl is born. It will grow, but only rarely to the perfectly round shape that will grace a woman’s neck; most pearls are not even nearly round. And although many have beautiful color and luster, many do not. Thus there are good pearls and bad pearls.

There Are Good Blood Clots . . .

It’s the same (sort of) with blood clots in our arteries and veins: there are good clots and bad clots. (They have a nice red color, but no one ever said they were beautiful.) Like pearls, blood clots do not form by themselves, but rather as a response to some irritant. Depending on the type of irritant, we get clots that can save our lives or take our lives.

In normal, healthy blood vessels, the inner lining consists of a layer of flat-surfaced endothelial cells arranged in a tightly packed tiling pattern that is, for all practical purposes, perfectly smooth. Our blood, including the myriad cells and microparticles it contains, flows easily through our 60,000 miles (not a typo!) of blood vessels, as though they were made of Teflon. Under these circumstances, no clots can form. That’s good, because we don’t want any clots, except when our blood vessels suffer traumatic injury—and then we need them.

If a blood vessel is cut or torn, it suddenly has an edge—a major imperfection—which exposes the structural layers underlying the endothelial cells. These layers contain, among other things, fibrils of collagen, a protein that blood platelets see as an irritant. (Other things irritate platelets too—see the sidebar for a primer on platelets.)

Blood Platelets

They’re called platelets because they somewhat resemble tiny plates. Each drop of your blood contains about 10 million of them. Often when blood tests are done, the sample is centrifuged so that its principal components will separate into layers that can be examined separately. At the bottom of the centrifuge tube is the heaviest component, consisting of red blood cells. Next is a very thin layer of white blood cells. Above that is a somewhat thicker layer of platelets, which are straw-colored. Overlying all of these is the yellowish plasma, which is just water containing a great variety of dissolved chemical compounds, both organic and inorganic.

Platelets are the tiniest cells in your body. Actually, they’re membrane-bound cell fragments formed by shedding from the cytoplasm of giant cells called megakaryocytes, which are found in bone marrow. Platelets have no nuclei (but neither do red blood cells). Their lifespan in the circulation is about 10 days.

The one function of platelets is to promote blood coagulation, or clotting. With essential help from vitamin K, the coagulation vitamin, they usually do this very well—sometimes too well for our own good, which is why anticoagulant drugs were developed. When provoked by some irritant, platelets change their shape, becoming globular, and they secrete a variety of chemicals that initiate the clotting cascade. They also become sticky, causing them to adhere to the irritant and to each other. Once this process of aggregation, or clumping, begins, it never spontaneously reverses—the platelets do not “unclump.”

The platelet aggregates become part of a gelatinous clot, or thrombus, which consists mainly of red blood cells (white cells too), all trapped in a fibrous network of an elastic, insoluble protein called fibrin. Some drugs, called thrombolytic agents, can be effective in dissolving clots (thus saving lives), especially if used within the first 2 hours or so after a heart attack, thrombotic stroke, or pulmonary embolism. They mimic the effect of a natural thrombolytic enzyme called TPA (tissue plasminogen activator), which is produced by endothelial cells. TPA itself is also used therapeutically, in the form of molecules produced by genetic engineering techniques.

Among the many compounds that promote platelet aggregation are: coagulation factors, such as thrombin; certain hormones, such as epinephrine and vasopressin; certain small organic compounds, such as serotonin and adenosine diphosphate; certain lipid derivatives, such as platelet aggregating factor (PAF) and thromboxane A2; and certain proteins, such as collagen and immune complexes.

All in all, platelets are easily aggravated into aggregating—so be nice to your platelets!

The platelets’ immediate response is to become sticky so that they adhere to the collagen and to each other. They also launch a complex cascade of chemical reactions in the blood, leading to the formation of a thrombus (blood clot) to stop the bleeding at the wound site; vitamin K is essential for this process. Were it not for this protective mechanism, we could bleed to death from even a relatively minor injury. (Until the advent of modern treatment methods, this was often the fate of hemophiliacs, who lack one or more of the enzymes required for the clotting cascade.)

. . . And Bad Blood Clots

So much for the good clots. Now we come to the bad ones (and, as we will soon see, a way to help prevent them from forming). You know what the bad clots are: they’re the ones that can obstruct a coronary artery, causing a heart attack; or a cerebral artery, causing a stroke; or a pulmonary (lung) artery, a condition called pulmonary embolism.* Any of these blockages, if severe enough, can kill you on the spot. As bad clots go, it doesn’t get much worse than that.

*An embolism is the obstruction (also called occlusion) of a blood vessel by an embolus, which is a thrombus that has broken loose from its moorings. Pulmonary embolism doesn’t have a common name that’s analogous to heart attack or stroke, but it can be just as deadly.

But how do blood clots form inside blood vessels that have not been injured? They don’t—clots are also triggered by nontraumatic injuries. The most common such injury is an atherosclerotic plaque, which builds up over time and gradually restricts the flow of blood through the vessel where it resides. Plaques consist not just of cholesterol but also, typically, of other lipids, lipoproteins (especially if they’ve been oxidized by free radicals), a variety of cellular debris, and platelets; they may also contain calcium deposits.

How a Tiny Imperfection Can Lead to Disaster

Platelets play a key role in the origin of a plaque deposit. The process is believed to begin when tiny nicks (imperfections) appear in the formerly pristine surface of the endothelium; these microinjuries can be caused by hypertension (high blood pressure), hyperglycemia (high blood sugar), or chronic inflammation arising from such diverse factors as stress, anger, periodontal disease, and sexually transmitted diseases. They can also be caused by toxins, such as nicotine and the natural amino acid homocysteine (if the latter is present at excessive levels).

Whatever its origin, an endothelial nick can induce irritated platelets to become sticky, causing them to aggregate at the site, which can then serve as a nucleation site for the accumulation of lipids and other materials that will develop into an atherosclerotic plaque. Eventually, in many cases, the plaque itself serves as a host site for the formation of a thrombus, again caused by platelet aggregation. The thrombus becomes integrated into the plaque structure, and the plaque may remain stable indefinitely, causing no problem other than the restriction of blood flow.

But sometimes a plaque will rupture, releasing the thrombus and other debris into the bloodstream. The thrombus is now an embolus, which will probably wind up causing obstruction—complete blockage—of a vessel too small to allow it to pass. If so, it will kill the tissues that were served by that vessel, and if those tissues . . . well, you know the rest.

Aspirin Is Effective—Unless It Isn’t

How can we prevent all this from occurring? The usual ways: good diet, regular exercise, no smoking, etc. And aspirin, whose beneficial effects in preventing cardiovascular disease are well documented. Aspirin works mainly by inhibiting platelet aggregation, thus reducing the tendency toward thrombosis, or clot formation. This is especially important for people at high risk for serious vascular events, such as heart attack or thrombotic stroke (stroke caused by obstruction of a cerebral artery).

On the other hand, too much aspirin, taken chronically, can be harmful: it can cause gastrointestinal disturbances and internal bleeding, and it can raise the risk for hemorrhagic stroke, the kind caused by a ruptured blood vessel in the brain. That’s why most doctors recommend the daily use of “baby aspirin” (81 mg, or 1/4 of a regular aspirin) for helping to prevent cardiovascular (and cerebrovascular) disease—it’s considered effective but not excessive.

But what if aspirin is not effective (or poorly effective) because the individual doesn’t respond well to it? According to a team of researchers from Hungary and the United States, up to 20% of serious vascular events in high-risk patients are attributable to aspirin resistance, a failure of aspirin to inhibit platelet aggregation effectively.1 Clinical studies cited by these authors have shown a significant correlation between aspirin resistance and heart attacks and strokes in patients with stable cardiovascular disease, resulting in an increased risk of death.

Resveratrol to the Rescue

Thus there is an obvious need for good alternatives to aspirin, and the researchers believe they have found one in the plant polyphenol resveratrol. This is the red-wine compound widely believed to explain (at least in part) the “French paradox,” the unexpectedly low incidence of heart disease in the French, whose diet is rich in fats. It’s also, however, rich in red wine, nature’s best source of resveratrol, whose many health benefits have fueled an explosion of scientific interest in this remarkable compound.*

*For more on some of the health and longevity benefits of resveratrol, see “Resveratrol May Be a Longevity Molecule” (November 2003), “Resveratrol and Quercetin—Puzzling Gifts of Nature” (July 2005), “Resveratrol Fights Brain Plaque” (November 2005), “Can Resveratrol Help Prevent Alzheimer’s?” (February 2006), “Resveratrol Prolongs Life in a Vertebrate!” (April 2006), and “Resveratrol—Star Molecule Against Disease and Aging” (August 2006).

Because resveratrol, in addition to its other cardioprotective properties, is known to inhibit platelet aggregation,2 the Hungarian/American research team decided to test its effectiveness in blood samples taken from high-risk cardiac patients who were classified as either aspirin-sensitive (good inhibition of platelet aggregation by aspirin) or aspirin-resistant (poor inhibition). The latter was defined as a higher than expected (by 40% or more) aggregation of platelets in the presence of either of two compounds that are known to promote aggregation: collagen and the hormone epinephrine (aka adrenaline). In these cases, in other words, aspirin failed significantly to produce the expected inhibition of platelet aggregation. (That’s bad news for people who think they’re getting this particular cardiovascular benefit from aspirin, but aren’t.)

Resveratrol Is Especially Helpful for Aspirin Nonresponders

The study entailed 50 high-risk cardiac patients who were taking at least 100 mg of aspirin daily; of these patients, 31 (62%) were aspirin-sensitive, and 19 (38%) were aspirin-resistant, according to the tests done on their blood. The researchers treated the blood samples with collagen or epinephrine to stimulate platelet aggregation, with or without simultaneous treatment with resveratrol to inhibit aggregation.*

*Limitations of this study include the fact that it was a laboratory study, not a clinical trial. Also, the bioavailability of resveratrol in humans is known to be very low: it’s fully metabolized by the liver within minutes, but its metabolites are conjectured to have similar biological activity. Finally, little is known about the possibly important complementary role of many other polyphenolic compounds found in resveratrol-containing foods.

In the blood from the aspirin-resistant patients (whose platelet aggregation levels were high), resveratrol significantly reduced the maximum degree of aggregation, indicating that it was effective where aspirin was not. In the blood from the aspirin-sensitive patients (whose platelet aggregation levels were low), resveratrol’s action was different with the two aggregation stimulants: with collagen, resveratrol had only a marginal effect, but with epinephrine, it had a significant effect, reducing the aggregation level even further than aspirin had.

Resveratrol is believed to inhibit platelet aggregation in several ways, one of which is the same as that of aspirin’s mechanism: inhibition of the proinflammatory enzyme cyclooxygenase-1 (COX-1).2 Aspirin’s effectiveness, however, seems to be age-related: in the Hungarian/American study, 26% of the patients under the age of 60 were aspirin-resistant, whereas 45% of the patients aged 60 or older were aspirin-resistant. Thus the need for an alternative to aspirin becomes statistically greater with advancing age. The authors stated,1

Our study suggests that ASA [aspirin] nonresponders may obtain significant benefits from an increased resveratrol intake with respect to cardiovascular events. . . . Collectively, dietary intake of resveratrol and related polyphenols is likely to exert significant cardioprotective effects, in part by inhibiting platelet aggregation. We propose that high-risk cardiovascular ASA-R [aspirin-resistant] patients will especially benefit from resveratrol consumption.

Eat and Drink Well—and Supplement Well

Although little is known about the effects of diet and nutrition on blood platelets, recent epidemiological, clinical, and laboratory studies have shown that diets that have strong antioxidant and anti-platelet-aggregating properties appear to lower the risk of death from cardiovascular disease.2 Notable among the foods with these properties are fruits, vegetables, grains, green tea, and red wine.

In terms of health benefits, the star molecule in red wine is resveratrol, which is known to have antioxidant, anti-inflammatory, antifungal, antimutagenic, anticancer, neuroprotective, and antiaging properties. As a bonus, it may also beat aspirin at its own game in terms of cardiovascular protection. Its antioxidant properties may be important in this regard, because the suppression of reactive oxygen species, including free radicals, is known to be a factor in the inhibition of platelet aggregation.

Does all this good news about resveratrol stir your blood? Good—that means it’s not clotting. Let’s keep it that way, shall we?


  1. Stef G, Csiszar A, Lerea K, Ungvari Z, Veress G. Resveratrol inhibits aggregation of platelets from high-risk cardiac patients with aspirin resistance. J Cardiovasc Pharmacol 2006;48:1-5.
  2. Olas B, Wachowicz B. Resveratrol, a phenolic antioxidant with effects on blood platelet functions. Platelets 2005;16:251-60.

Will Block is the publisher and editorial director of Life Enhancement magazine.

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