The nutritional and medicinal value of grapes has been touted for hundreds of years. While the general composition of the grape consists of two-six percent stem, five-12 percent skin, 80-90 percent juice and zerofive percent seeds, the grape’s major component is a class of compounds known as polyphenols—the most important phytochemicals found in the fruit. Grapes’ phytochemicals possess a variety of biological activities and offer many health benefits.1,2
The French Paradox
The French, despite their greater intake of fat and saturated fat experience, have less cardiovascular disease than other Westerners. This is believed to be due, at least in part, to the French consumption of red wine (red grapes).3
The main polyphenols include anthocyanins (that give purple and red grapes their characteristic color), flavanols, stilbenes (resveratrol) and phenolic acids.Anthocyanins and resveratrol are found mostly in the skin of the grape, whereas the grape seed contains higher amounts of flavonoids such as catechins and proanthocyanidins. Grape seed extract has been studied for its powerful antioxidant properties, which help provide protection against cardiovascular disease, cancer as well as inflammatory and agerelated conditions.4-6
Grape Seed Extract
Antioxidant Properties
A major risk factor for cardiovascular disease is the oxidation of LDL cholesterol, a significant mechanism that leads to the development of atherosclerosis. The antioxidant characteristics of grapes include scavenging of free radicals and inhibition of lipid oxidation.7 The highest antioxidant activity is found in grape seeds, followed by skin, and the flesh demonstrated the lowest antioxidant activity.
8 The antioxidant effects of grape seeds are due mostly to their content of proanthocyanidins, which have 15-20 times the antioxidant activity of vitamin E and 50 times that of vitamin C.9
Two groups of volunteers were given a high fat meal, while one group also received 300mg of grape seed extract.Post-meal blood analysis revealed a 1.5 fold increase in oxidized fats in the blood of those individuals not given grape seed extract.10 Researchers concluded that grape seed extract has a significant antioxidant effect, and one that may reduce the amount of oxidized lipids that contribute to the atherosclerotic process.
Catechin and proanthocyanidin B4, two major polyphenolic compounds extracted from grape seeds, were found to induce antioxidant enzymes superoxide dismutase, catalase, GSH (glutathione), and GST (a phase 2 enzyme involved in the detoxification of reactive oxygen species).11 Overall, the powerful antioxidant effects of various components of grape seed extract are believed to play a significant role in the cardio-protective effects of grape seed extract.
Blood Vessel Function
Markers of vascular risk that have received much attention include endothelial dysfunction, vascular inflammation, oxidative stress and insulin resistance.
The endothelial cells that line blood vessels are critical to healthy blood vessel function. They play a major role in maintaining healthy blood pressure, arterial flexibility and limiting the formation of plaque and the tendency for excess blood clotting. Several factors play a role in endothelial function, including the production of the important signaling molecules nitric oxide and endothelin-1, both of which are beneficially affected by grape seed polyphenols. One study reported that grape seed extract both improved endothelialdependent vasodilator response and decreased the synthesis of endothelin-1, a potent vasoconstrictor.12 Grape seed extract also helps to activate endothelial nitric oxide synthase (e-NOS) and cause an endothelium-dependent relaxation (EDR) of blood vessels.13 Flow-mediated dilation is a commonly used measure of blood vessel dilation (relaxation).
Consumption of 2g of grape seed extract daily could improve flow-mediated dilation in healthy adults. Researchers suggested that this is likely influenced by the ability of grape seed extract to regulate nitric oxide production.14 Grape seed extract has been shown to effectively lower blood pressure. At a dose of either 300mg daily or 150mg daily, grape seed extract reduced both systolic and diastolic blood pressures in subjects with the metabolic syndrome.15 A meta-analysis by researchers from the University of Connecticut and Yale University revealed significant reductions in blood pressure (-1. 54 mm Hg) and heart rate (-1.42 bpm) in human subjects taking grape seed extract. These changes may seem small, but lead author Craig Coleman of the University of Connecticut stresses that a little change can go a long way.16
Inflammation
Inflammation is a major component of many chronic diseases including cardiovascular disease, diabetes and obesity.
Studies have revealed potent anti-inflammatory properties of proanthocyanidins; possible mechanisms seem to be related to free radical scavenging, inhibition of inflammatory cytokines and reduced lipid peroxidation.17,18 Treatment of inflammatory diseases could be mediated by controlling the overproduction of inflammatory mediators such as PGE2 and nitric oxide.Grape seed proanthocyanidins demonstrate an ability to modulate the inflammatory response by inhibiting the excess production of nitric oxide and PGE2.19 Grape seed extract has also been shown to improve inflammatory markers in highrisk obese type-2 diabetic subjects with one study showing a 40 percent reduction in C-reactive protein (CRP).20 The altered production of proinflammatory molecules by adipose tissue has been implicated in the metabolic complications of obesitThe adipose tissue of obese individuals produces increased amounts of proinflammatory compounds.21 The daily consumption of grape seed procyanidins help prevent both systemic and local lowgrade inflammation in adipose tissue, muscle and liver, which might improve obesityinduced insulin resistance in these tissues.22 Grape seed extract and its associated active compounds show great promise in helping to influence the inflammatory process and inflammatory- related conditions.
Cancer
Procyanidins isolated from grape seed have some activities in inhibiting tumor growth.23 Malignant glioma is the most common malignant tumor that occurs in the central nervous system. Cell studies show that F2, an oligomeric procyanidin isolated from grape seed extract could inhibit cell growth and viability of human malignant glioma U-87 cells.24 In a more recent study on human glioblastoma U-87 cells, researchers suggested that F2 from grape seed extract induces a type of programmed cell death known as paraptosis.25 Unlike other types of programmed cell death, paraptosis works via different biochemical mechanisms with the result being the same: death of cancer cells. Abnormalities in cell cycle progression provide cancer cells with the unlimited potential to replicate, and therefore targeting regulators of the cell cycle can be a potential chemopreventive strategy. Agarwal and colleagues demonstrated the ability of grape seed extract to up-regulate levels of p21 protein in Ht29 cells (human colon carcinoma cells) both in vitro and in vivo. Low levels of p21 are implicated in metastasis of colorectal cancer.26
More recently this same group delineated the molecular mechanisms responsible for grape seed extract’s affects on p21 showing that grape seed extract mediates the activation of several pathways involved in up-regulating p21 levels.
These findings suggest that grape seed extract could be a potential chemopreventive agent due to its ability to help regulate the growth of colorectal cancer HT29 cells by acting on p21, an essential regulator of cell cycle progression and cell growth.27 Back in 2000-2002, the VITAL (VITamins And Lifestyle) study began with 77,738 men and women, aged 50-76 from western Washington State completing a baseline questionnaire.The aims of this cohort study are to investigate the associations of supplement use with cancer risk. Specific aims focus on the associations of vitamin C, E, calcium, fiber and other supplements with prostate, breast, lung, colorectal, melanoma, bladder, blood/lymph and total cancer incidence and total mortality.
In a recent follow up study on the VITAL cohort, researchers looked at the role of specialty supplements and cancer risk Results showed a 40 percent reduction in prostate cancer risk among those men taking grape seed extract.28
Conclusions
The major effects of grape seed extract include improved cardiovascular health, mostly related to grape seed extract’s ability to increase nitric oxide production, decrease platelet aggregation, limiting the oxidation of LDL cholesterol and increasing the activity of numerous other antioxidants in the body i.e. glutathione. The ability of grape seed extract to effectively modulate several biochemical/physiological processes associated with inflammation has wide reaching affects on most chronic diseases. Results from a variety of experiments indicate proanthocyanidins may help regulate a number of key reactions involved in the cancer process. We must continue to fund research that can help identify other biologically active components of grape seed extract, and continue to try and elucidate the mechanisms of action at the cellular and molecular biological levels that will help provide further insight into proper dosing.
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