Resveratrol Instead of Aspirin for Heart Health

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Article Title: Resveratrol Instead of Aspirin for Heart Health

Article 11/1/2006

 

 

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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.

 

 

 

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*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.

 

 

 

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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.*

 

 

 

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*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).

 

 

 

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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.*

 

 

 

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*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.

 

 

 

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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?

 

References

 

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.

Olas B, Wachowicz B. Resveratrol, a phenolic antioxidant with effects

on blood platelet functions. Platelets 2005;16:251-60.

 

 

 

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Will Block is the publisher and editorial director of Life

Enhancement magazine.