Contained within each grape seed is the kernel of a cornucopia of benefits …

More Grape Expectations

Grape seed extract provides more avenues
to better health than previously realized
By Will Block


or millennia, fermented beverages have played a significant role in most societies throughout the world. In the beginning, our ancestors created beer, sake, and wine from grain, rice, and grapes. Although beer is thought to be the oldest of the three beverages, dating back to the early Neolithic period, about 9500 BC, wine too has a rich history and was probably first made around 8000 BC, at the dawn of the agricultural revolution. Archaeologists have found evidence of grape seeds and therefore, presume the likelihood of wine making in the Near East at Catal Huyuk in Turkey, Damascus in Syria, and Byblos in Lebanon.1

One of the earliest domesticated grape varieties, Vitis vinifera subsp. vinifera—along with its wild relative, V. vinifera subsp. sylvestris—was widely cultivated and prized for the quality of its fruit and its ability to produce wine. The present evidence supports a Near East origin for vinifera and demonstrates the incorporation of genes from sylvestris, as the grape moved into Europe, where wine making has ultimately achieved its highest levels of expression.2

Outside the Normal States of Mind and Emotion

Throughout recorded history, the story of wine runs parallel to culture for several reasons: its use as a food, as a medicine, and as a solvent for extracting plants and animal tissues in the preparation of medications.3 As well, wine has been employed as a therapeutic agent, not to mention its role as an important element in religious and social life. This is undoubtedly owing to its value as an inebriant and the exhilarant, allowing the imbiber to step outside the normal states of mind and emotion.

When thought of as a food, wine is the naturally fermented juice of the grape with all of the grape’s essences and virtues. But also, it is something more, evolving as it ages and changes biologically. Optimally, depending on its variety and the skill of the wine maker, it appreciates over a temporal lifespan, a period during which it may be savored.

Is There Something More to Wine?

But there is much more to wine and the grapes with which it is made. This, we are continuing to learn. As the French Paradox* lent credence to, there are health benefits attributable to the moderate consumption of wine, especially with regard to cardiovascular function. But what is it in wine that is responsible for this advantage. Is it resveratrol? Is it the alcohol? Or is it something else? See “Inhibition of Platelet-Derived Growth Factor Beta by Red Wine May Help Explain the French Paradox,” in Durk Pearson & Sandy Shaw’s Life Extension News, 6(1), February 2003 and “Could the French Paradox and the Benefits of the Mediterranean Diet Be Partly Due to Activation of the Niacin Receptor?” in Durk Pearson & Sandy Shaw’s Life Extension News, 12(3), June 2009.

* The French, who eat relatively high-fat diets, have a mortality rate for coronary artery disease that is only about 50% compared with other European countries and the U.S. A seeming paradox.

When wine is made, the must—the freshly pressed grape juice that also contains the skins, seeds, and stems of the fruit along with derivatives of the soil—undergoes chemical changes during fermentation. These processes result in a wide range of biologically active constituents, including alcohols, aldehydes, acids, esters, polyphenols, anthocyanins, nitrogenous compounds, enzymes, vitamins, and traces of carbohydrates. Then there are also inorganic constituents, minerals, acids, and salts. The aroma and bouquet of wine, aspects that significantly contribute to its enjoyment, are the result of the aromatic assembly that is the byproduct of the aldehydes, volatile and fixed acids, esters, and other compounds yet to be defined, which are released during fermentation and remain viable within the lifespan of the wine.

Not surprisingly, there are many components and aspects of wine and grapes to consider for their health benefits, and among the most promising—along with their stems, skins, and even the soil in which vines are grown which contribute to the chemical composition of the finished product—are the grape seeds.

The DNA of Grapes

Resveratrol, a polyphenol found especially in red wine, is definitely not present in amounts that are optimal for health. This is true as well for grape seeds, which contain among other compounds, proanthocyanidins. These 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.)

Grape seed extract has a significant
potential for therapeutic use in
tauopathies such as AD.

Without flavonoids, we would almost certainly 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.

But as stated above, it is not possible to gain the optimal amount of grape seed health benefits by drinking wine or even consuming the seeds found in grapes as a wealth of material has demonstrated. It is only grape seed extract that permits us to gain the cornucopia of health benefits found in the polyphenols within these carriers of the plant’s DNA. The abundance of grape seed extract’s benefits include the ability to counter oxidative stress, protect circulation, and provide anti-inflammatory and anticancer effects. And there is so much more …

Brain Seeding

Just recently, researchers at the Mount Sinai School of Medicine in New York City and the James J. Peters Veterans Affairs Medical Center in Bronx, NY assessed the effect of grape seed extract (GSE) on the structure of hyperphosphorylated* tau protein isolated from Alzheimer’s disease (AD) brain tissue.4 When this protein becomes abnormally folded, the result leads to the aggregation of tau into neurofibrillary tangles, one of the major hallmarks of AD.

* Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. This process can activate or deactivate many protein enzymes, thus causing or preventing the mechanisms of diseases such as cancer, diabetes, and Alzheimer’s disease.

As a class of neurodegenerative diseases, tauopathies are characterized by the pathological aggregation of tau protein in the human brain. AD is such a tauopathy.

In a mouse model of tauopathy, the same researchers had recently shown that GSE reduces tau pathology. In their current research, through the use of transmission electron microscopy the scientists wanted to see the effects of GSE on the form and shape of tau aggregated tissue and what they saw was the partial disintegration of the tauopathic filaments that comprise some of the aggregated tissue. The filaments showed an approximate doubling in width and displayed numerous protrusions and outspread ends consistent with the unfolding of tau and reduced structural stability. This meant that they were less dominant in corrupting brain function.

Overcoming the Tau

Also, GSE induced a reduction in something called immunogold labeling, a staining technique used in electron microscopy. This indicated a reduction in antibody activity and represented immune enhancement. While the researchers thought it was unlikely that alterations in immunogold labeling were due to biochemical changes, they concluded that the GSE mechanism may include an interaction of polyphenols with proline* residues in the proline-rich domain of tau. Taken together, the results suggest that GSE has a significant potential for therapeutic use in tauopathies such as AD by disrupting fibrillary conformation, the protein aggregation that leads to the disintegration of normal protein structures.

* Ironically, the amino acid proline is one of the principal organic osmolytes in the mammalian brain that has been found to protect an aggregation-prone protein.

A diverse group of neurodegenerative diseases are characterized by progressive, age-dependent formation of misfolded protein aggregates. Among these are AD, Huntington’s disease, Parkinson’s disease and a number of taumediated disorders. There is currently no effective treatment for any of these disorders. However, because these neurodegenerative disorders all share a common mechanistic theme in the depositions of misfolded protein, GSE is under examination as a potential treatment because it has been shown to be capable of interfering with the formation and/or stability of misfolded protein aggregates.

GSE Corrects Misfolded Proteins

In another recent paper, researchers reviewed the accumulating evidence that GSE is effective both in vitro and in vivo for mitigating certain misfolded protein-mediated neuropathologies.5 Also reviewed was evidence regarding the bioavailability of GSE components in the brain along with the tolerability and safety of GSE in animal models and in humans. In conclusion, the available information indicates that GSE has a future for treating a variety of neurodegenerative disorders that involve misfolded protein-mediated neuropathologic mechanisms.

Another study reported that small-molecule inhibitors—including polyphenolic compounds such as curcumin, (-)-epigallocatechin gallate (EGCG), and GSE—have been shown to reduce amyloid beta aggregation through distinct mechanisms, and have shown effectiveness at reducing amyloid levels when administered to transgenic mouse models of AD.6 One other study indicated that several other tauopathies, including progressive supranuclear palsy and corticobasal degeneration may be treatable by GSE.7

Diabetes and Grape Seed Extract

At the Academic Unit of Diabetes and Endocrinology, Queen Alexandra Hospital in Portsmouth, UK, researchers hypothesized that many of the markers of type 2 diabetes such as vascular risk due to endothelial dysfunction, oxidative stress, inflammation and insulin resistance could be addressed by GSE.8

In their study, 32 type 2 diabetics (16 men and 16 women) who were prescribed diet or oral glucose-lowering agents, also received GSE (600 mg/day) or placebo for 4 weeks in a double-blinded randomized crossover trial. This study aimed to determine if GSE could improve these markers in high-risk cardiovascular subjects with type 2 diabetes. At the baseline means, the age was 61.8 ± 6.36 years; the body mass index was 30.2 ± 5.92 kg/m2 (30 is the threshold for obesity); and the duration of the subject’s diabetes was 5.9 ± 2.14 years.

Markers of endothelial function, oxidative stress, reduced glutathione/oxidized glutathione, inflammation (CRP), urinary albumin:creatinine ratio, insulin resistance and metabolism were measured at baseline and after intervention with GSE or placebo.

Grape seed extract may have a
therapeutic role in
decreasing cardiovascular risk in
type 2 diabetics at high risk.

Following GSE (but not placebo), significant changes were noted in metabolism, whole blood glutathione, and CRP. At the same time, total cholesterol concentration was found to have decreased. No statistically significant changes were shown in endothelial function, insulin resistance, or oxidative stress. GSE significantly improved markers of inflammation and glycemia. It also improved a single marker of oxidative stress. These results, in obese type 2 diabetic subjects at high risk of cardiovascular events over a 4-week period, strongly suggest that GSE may have a therapeutic role in decreasing cardiovascular risk.

Arginine and GSE Aid for the Untrained

Understanding the effects of GSE and the amino acid L-arginine on human performance was the goal of a study conducted at University of Nebraska-Lincoln in Lincoln, Nebraska.9 Employing 50 untrained subjects, the study purpose was to examine the effects of daily oral administration of an arginine-based supplement for 4 weeks on the physical working capacity at the fatigue threshold (PWCFT). Testing this effect required an electromyographic procedure for estimating the highest power output that can be maintained without neuromuscular evidence of fatigue.

There are few nutrients possessing as
many probable and possible arenas of
benefit as grape seed extract.

Using a double-blind, placebo-controlled design, the subjects were college-aged men (mean age was 23.9 ± 3.0) randomized into 3 groups: placebo (n = 19); 1.5 g arginine (n = 14); or 3.0 g arginine (n = 17). The 1.5-g arginine group ingested the designated amount of arginine along with 300 mg of GSE, whereas the 3.0 g arginine group ingested the designated amount of arginine and 300 mg of GSE. Every subject performed an incremental test to exhaustion on a cycle ergometer to determine their PWCFT prior to supplementation and after 4 weeks of supplementation. Surface electromyographic signals were recorded from the Vastus lateralis, the largest part of the Quadriceps femoris in the thigh. At the end, there were significant mean increases in PWCFT for the 1.5 g (22.4%) and 3.0 g (18.8%) supplement groups, but no change for the placebo group. Arginine together with GSE supplementation was found to be an ergogenic aid to enhance physical performance in untrained individuals.

Nutrients Proven Safer and
More Effective Than Foods

Although few will admit it, the scientific evidence for foods—the ordinary stuff we eat every day—is weak. Yet that doesn’t stop us from attempting to choose the best foods we possibly can to make up our diets. What’s the best way to proceed, barring the double-blind, placebo-controlled studies that we take for granted in other areas?

Aside from overblown concerns about contamination—about which the President and the FDA wail, “Food safety is part of our citizens’ basic contract with the government,” they assert—the food should first have a long history of use, and there should be no known toxicity associated with it. Finally, epidemiological data should not conflict, and they should preferably affirm that there are no harmful aspects of the food. Many foods do not pass these tests, especially since most of the natural chemical compounds of which most foods are comprised have never been tested. It is estimated that less than 5% of the composition of most foods has been subject to the kind of scrutiny that vitamins and other established nutrients have undergone.

The Cornucopia of Grape Seed Power

There are few nutrients possessing as many probable and possible arenas of benefit as grape seed extract. The cornucopia (from Latin, Cornu Copiae) is a symbol of food and abundance dating back to the 5th century BC. In Greek mythology, Amalthea—who in her totemic form was a she-goat—raised Zeus, the king of the gods, on her breast milk in a cave atop a mountain on the island of Crete. While playing together, Zeus accidentally broke off her horn, and restored it as compensation. However, her horn was supernaturally empowered. Thereafter, possessing it conferred whatever the holder wished for.

Depicted originally as a goat’s horn abundantly filled with fruits and flowers, deities (especially Fortuna, the goddess of fortune and personification of luck in the religion of ancient Rome) were shown with it: the horn of plenty. But if you have the abundance of good science emerging for a nutrient such as GSE, you don’t need mythology to fill your horn of plenty—with plenty of good health.


  1. Johnson H. Vintage: the story of wine. London: Mitchell Beazley Publishers;2006.
  2. Myles S, Boyko AR, Owens CL, Brown PJ, Grassi F, Aradhya MK, Prins B, Reynolds A, Chia JM, Ware D, Bustamante CD, Buckler ES. Genetic structure and domestication history of the grape. Proc Natl Acad Sci USA 2011 Jan 18. [Epub ahead of print]
  3. Lucia SP. Wine: a food throughout the ages. Am J Clin Nutr 1972 Apr;25(4):361-2.
  4. Ksiezak-Reding H, Ho L, Santa-Maria I, Diaz-Ruiz C, Wang J, Pasinetti GM. Ultrastructural alterations of Alzheimer’s disease paired helical filaments by grape seed-derived polyphenols. Neurobiol Aging 2010 Dec 31. [Epub ahead of print]
  5. Ho L, Pasinetti GM. Polyphenolic compounds for treating neurodegenerative disorders involving protein misfolding. Expert Rev Proteomics 2010 Aug;7(4):579-89.
  6. Dasilva KA, Shaw JE, McLaurin J. Amyloid-beta fibrillogenesis: structural insight and therapeutic intervention. Exp Neurol 2010 Jun;223(2):311-21.
  7. Pasinetti GM, Ksiezak-Reding H, Santa-Maria I, Wang J, Ho L. Development of a grape seed polyphenolic extract with anti-oligomeric activity as a novel treatment in progressive supranuclear palsy and other tauopathies. J Neurochem 2010 Sep;114(6):1557-68.
  8. Kar P, Laight D, Rooprai HK, Shaw KM, Cummings M. Effects of grape seed extract in Type 2 diabetic subjects at high cardiovascular risk: a double blind randomized placebo controlled trial examining metabolic markers, vascular tone, inflammation, oxidative stress and insulin sensitivity. Diabet Med 2009 May;26(5):526-31.
  9. Camic CL, Housh TJ, Zuniga JM, Hendrix RC, Mielke M, Johnson GO, Schmidt RJ. Effects of arginine-based supplements on the physical working capacity at the fatigue threshold. J Strength Cond Res 2010 May;24(5):1306-12.

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

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