Stay Healthy with Grape Seed Extract

Grape Seed Extract Helps
Prevent Atherosclerosis

In human trial, it reduces the oxidation of LDL-cholesterol,
the primary factor in plaque formation
By Will Block

“Punching the cap” of grape skins (and seeds) in fermenting wine.
re you well bred? Would you make the cut for a cocktail party at some socialite’s mansion in the Hamptons? Being filthy rich isn’t enough, of course—you must also be of good extraction, meaning that you have to have the “right” kind of family, schooling, occupation, political affiliation, etc. Bleh! It’s enough to make you choke on your glass of Viognier from that trendy new boutique winery in Sonoma County.

Speaking of wine, you probably know that Viognier is white, and white wines are fermented “off the skins,” which means that they don’t get the chance to extract much of the chemical bounty found in the grapes’ skins—or in the seeds, which are also left behind when the juice is pressed from the grapes. That treasure trove of molecules does, however, infuse red wines, which are fermented on the skins (and the seeds) for a few days—that’s what makes them red.

Proanthocyanidins Are Colorful and Healthful

The color comes from chemical compounds called proanthocyanidins, which are but one type of a broader class of compounds called flavonoids. What a dull world it would be without flavonoids, the plant pigments that give most flowers, herbs, vegetables, and fruits (including berries) their beautiful, bright colors, such as red, orange, yellow, blue, and purple. (Green comes mostly from chlorophyll, which is not a flavonoid.)

Without flavonoids, we would probably be less healthy. That’s because all flavonoids are polyphenols, a type of compound associated with strong antioxidant properties in laboratory experiments and with a variety of health benefits in vivo (in living creatures). Although scientists now believe that these benefits have little or nothing to do with the polyphenols’ antioxidant properties (which are virtually nonexistent in vivo), they are no less real for that, and we can be grateful that they do occur. We can thank, among many other compounds, the proanthocyanidins in grapes and red wine.*

*White wines too are healthful, just not as much so as red wines. The alcohol itself is believed to be beneficial, which is why virtually all alcoholic beverages have potential health benefits—but only when consumed in moderation, i.e., nowhere near the level of inebriation.

Oxidized LDL-Cholesterol Is Bad

Ironically, although most polyphenols do not show antioxidant activity in vivo, the health benefits attributed to them may be due in part to antioxidant mechanisms that involve other compounds whose actions are triggered by the polyphenols, via biochemical pathways that are not yet well understood. One such antioxidant mechanism of particular importance is inhibition of the oxidation of LDL-cholesterol (the “bad cholesterol”).

High levels of LDL-cholesterol are harmful to our health mainly because this substance is highly susceptible to becoming oxidized by reactive oxygen species, including free radicals. When that occurs, the LDL-cholesterol tends to produce atherosclerotic plaque in our arteries—a major risk factor for heart attack and stroke.

Thus, we want to keep our LDL-cholesterol low to begin with (but not too low, because it’s vital—we couldn’t live without it), and we want to prevent the LDL-cholesterol we do have from becoming oxidized. The latter objective is where grape seed extract, which is rich in proanthocyanidins, may be helpful. (The extract is also rich in the celebrated longevity compound resveratrol, which is a polyphenol but not a flavonoid, and therefore, of course, not a proanthocyanidin.)*

*For more on grape seed extract and resveratrol, see “Revolutionary Antiaging Discovery with Resveratrol” (January 2007) and “Grape Seed Extract May Inhibit Fat Absorption” (July 2007).

Effects of Grape Seed Extract Studied

In Japan, a group of researchers from several corporations (including Kikkoman, the leading producer of soy sauce) and Wayo Women’s University in Chiba undertook a 12-week study of the effects of grape seed extract on two markers of human health, one negative and one positive:1 The study was randomized, placebo-controlled, and single-blind (double-blind is better).

© Mitiukhina
The negative marker of health was oxidized LDL-cholesterol. The positive marker was adiponectin, a hormonelike protein produced in adipocytes (fat cells); its principal effect is to enhance insulin sensitivity in peripheral tissues. This reduces the risk for type 2 diabetes, which is essentially an extreme form of insulin resistance and which opens the door wide to other degenerative disorders, including atherosclerosis. Low levels of adiponectin have been associated with increased risks for obesity, diabetes, and atherosclerosis.

For their study, the researchers used 53 healthy men and women, average age 52, whose plasma LDL-cholesterol levels were between 100 and 180 mg/dL (milligrams per deciliter). According to the American Heart Association, LDL-cholesterol levels can be rated as follows in terms of the risk for heart attack or stroke:

Less than 100 mg/dL


100 to 129 mg/dL

Above optimal

130 to 159 mg/dL

Borderline high

160 to 189 mg/dL


190 mg/dL or more

Very high

Thus the study subjects spanned the range from “above optimal” to “high.” (It’s useful to remember, by the way, that LDL-cholesterol levels are considered to be a more accurate indicator of cardiovascular risk than the more commonly cited total cholesterol levels.)

Grape Seed Extract Mitigates
Chloasma and Skin Cancer


Nobody likes their face to be marred by irregular brown splotches caused by hyperpigmentation, which is an excess accumulation of the skin pigment melanin. This condition, called chloasma (klo·AZ·ma) can be triggered by a variety of factors, by far the most common of which is sunlight. Pregnant women are especially susceptible to chloasma, which afflicts people of all races. The condition tends to improve or worsen depending on the amount of solar ultraviolet (UV) radiation they’re exposed to.

Treatment for chloasma is described as challenging and discouraging; in other words, it’s largely unsuccessful. Because it’s believed that UV-induced free radical reactions are involved in the formation of the hyperpigmented patches, researchers have tried various antioxidants, such as vitamins C and E, with some success. Other antioxidants may also be useful, and better treatments are being sought.

After achieving modest success using a proanthocyanidin-rich grape seed extract (GSE) to treat UV-induced hyperpigmentation in guinea pigs, a group of Japanese researchers at the Kikkoman Corporation tried it in a 12-month study of 12 nonpregnant women, average age 45, who had suffered from chloasma for an average of 12 years.1 The GSE used in this study contained 81% by weight of proanthocyanidins, and the amount of extract used was calculated to deliver 162 mg of these compounds daily.

The results were encouraging. Overall, the severity of chloasma was improved or slightly improved in 10 of the 12 women after 6 months, the time at which the maximum effect of GSE was seen. The women’s condition worsened during the seventh month, when they took no GSE. During the last 5 months of the study, when they were taking the GSE again, their condition did not improve any further.

Skin Cancer

It appears that GSE may have other, much more significant effects on skin. Researchers at the University of Alabama, Birmingham, reported recently that hairless mice exposed to UV radiation suffered far fewer, and much smaller, skin cancers when grape-seed proanthocyanidins were added to their diet than when they did not receive the supplement.2 With proanthocyanidins at 0.2% and 0.5% by weight of the mouse diet, the incidence of skin cancer was reduced by 20% and 35%, tumor multiplicity by 46% and 65%, and tumor size by 66% and 78%, respectively.

The researchers believe that this anticancer effect is mediated by the proanthocyanidins’ ability to inhibit suppression of the immune system by UV radiation, while simultaneously boosting the immune system via a related mechanism. These effects would make it more difficult for cancer to invade the skin.


  1. Yamakoshi J, Sano A, Tokutake S, Saito M, Kikuchi M, Kubota Y, Kawachi Y, Otsuka F. Oral intake of proanthocyanidin-rich extract from grape seeds improves chloasma. Phytother Res 2004;18:895-9.
  2. Katiyar SK. Dietary grape seed proanthocyanidins inhibit photocarcinogenesis through prevention of UV-induced suppression of immune responses via induction of interleukin-12 in mice. Abstract AGFD 011, American Chemical Society, 233rd national meeting, Chicago, March 25, 2007.

What Can You Extract from This?

Whenever you brew a pot of tea or coffee, you’re performing an extraction process: water-soluble solids are leached out of the leaves or beans, leaving the rest behind. Most herbal supplements, such as grape seed extract, are made by extracting soluble compounds from some ground-up part of the plant, using water or a suitable organic solvent; the water or solvent is then evaporated, leaving the extracted solids. These are very simple processes.

Far more complicated, and often requiring very sophisticated apparatus, are the kinds of extractions performed by research chemists, molecular biologists, and others, using innumerable substances, a great variety of solvents, and many different experimental methods. These provide the foundations for much of industrial chemistry and pharmaceutical manufacturing, including the preparation of many cosmetic products, drugs, and nutritional supplements.

Probably the most familiar example of an industrial extraction process is the production of metals from their ores. This was among mankind’s earliest applications of chemistry, starting about 5500 years ago in the early Bronze Age. In modern technology, however, it’s not just solids that get extracted from solid mixtures, but also solids from solutions, liquids from solids (e.g., oil from shale) or from liquid mixtures, and gases from solids, liquids, or gaseous mixtures. (In many cases, these processes are properly called separations, not extractions, but let’s not worry about the terminology.)

Take wine, for example. It’s basically a mixture of water and alcohol that contains hundreds of dissolved compounds (some are liquids, but most are solids in their pure state at room temperature). Because water and alcohol are mutually soluble, they can’t be separated as easily as, say, water and oil, which don’t mix.

There are, however, various methods by which the alcohol can be removed from wine. This leaves an aqueous solution that looks like wine because it still contains most of the dissolved compounds that gave the wine its distinctive characteristics. The health benefits are also retained—except, of course, for those that derive from the alcohol itself. (Actually, a bit of alcohol does remain, up to the legal limit of 0.5%.) The problem is that this “alcohol-free” wine tastes thin and watery compared with the real thing—alcohol is the true essence of wine.

Alcohol-free wine may seem like a classic case of Unclear on the Concept, but it does have two advantages over the real thing: a near-zero risk for intoxication and only about one-fifth as many calories. So it’s a boon for many people, such as dieters, designated drivers, pregnant women, people who must abstain from alcohol for medical reasons, and people who don’t like alcohol for whatever reason.

As with real wine, though, you would have to drink enormous amounts of alcohol-free wine (or, for that matter, plain old grape juice) to obtain the amounts of healthful proanthocyanidins, resveratrol, and other polyphenolic compounds that are readily available and affordable in the form of nutritional supplements.

Grape Seed Extract Inhibits Oxidation of LDL-Cholesterol

The grape seed extract used in the study contained 72% by weight of proanthocyanidins, and the amounts of extract used were calculated to deliver either 200 mg or 400 mg of these compounds daily. Compared with placebo, they had no effect on the blood levels of LDL-cholesterol per se, but they did produce a statistically significant reduction in the levels of oxidized LDL-cholesterol, with the higher dose showing the stronger effect (a 14% reduction).

There was no statistically significant effect, however, on adiponectin levels, nor were there any significant effects on total cholesterol, triglycerides, or any of a wide array of nonlipid components in the subjects’ blood. There were also no significant effects on body weight or blood pressure. There were appreciable increases in HDL-cholesterol (the “good cholesterol”), but oddly, this was true in the placebo group as well, and it turned out that there were no significant differences among the three groups in that regard.

Admit It—You Are Well Bred

The results of this study are consistent with those of other studies, both animal and human, indicating that grape seed extract has a beneficial effect in helping to reduce the oxidation of LDL-cholesterol. This effect is believed to play a role in the “French paradox,” the puzzling fact that the French have lower rates of cardiovascular disease than would be expected based on their exceptionally rich diet. It may be their copious consumption of red wine that does the trick, at least in part.

Whether or not you drink red wine, you can always add some grape seed extract to your supplemental diet, indicating that you have a sophisticated view of the importance of good nutrition for health and longevity. (That’s a sign of good breeding, you know.)


  1. Sano A, Uchida R, Saito M, Shioya N, Komori Y, Tho Y, Hashizume N. Beneficial effects of grape seed extract on malondialdehyde-modified LDL. J Nutr Sci Vitaminol 2007;53:174-82.

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

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