Anti-Aging | Anti-Oxidant
• As an antioxidant, Grape Seed Extract offers superior protection, which helps protect the body against harmful free radicals. Free radicals are recognized as a significant contributor to aging in the body. The antioxidant power of the proanthocyanidins (the primary polyphenol in Grape Seed and Grape Skin Extracts), is approximately 50 times greater than Vitamin C and 20 times greater than Vitamin E. (1) Free radicals have been associated with over 100 disease conditions, including advanced aging, atherosclerosis, Alzheimers disease, arthritis and cancer. Aging and the on-set of these diseases is the result of the accumulated damage to the cells and tissues from destructive free radicals.
• Grape seed extract is very bioavailable and protects against lipid oxidation and DNA damage, caused by free radicals, considerably better than other antioxidants (such as Vitamins C and E).(6) Grape Seed Extract has also been shown to be cytoprotective, particularly against DNA damage and resulting cell death in cases of drug toxicity, such as acetaminophen. (22)
• Alcohol (ethanol) consumption has been shown to produce many toxic effects in the body. In a study involving male rats, oral adminstration of ethanol resulted in impairments of the liver, brain, and testes. Furthermore, there was a reduction in male fertility, and decreases serum testosterone. Because of its action as a powerful antioxidant, grape seed extract (as part of a dual antioxidant formula), was shown to offer protection against ethanol toxicity, and reduce the effects of ethanol on the male testis, liver and brain. (research: in vivo / lab animals). (42)
• Significant ant-inflammatory effects have been shown with both Grape Seed Extracts and Grape Skin Extracts. (30, 31).One study demonstrated that the proanthocyanidins in Grape Seed Extract significantly inhibited the inflammatory response in lab animals in a dose dependent manner. (30)(research: in vivo / animals)
• Another study, examining the effects of Grape Seed and Grape Skin Extracts on platelet-dependent inflammatory responses (associated with acute cardiac events), showed the inhibition of platelet aggregation (anti-thrombotic), and platelet dependent inflammatory responses. The effect was additive, when Grape Seed Extract and Grape Skin Extract were combined. (31)(research: in vitro / cell culture)
• Grape Seed Extract polyphenols have been shown to inhibit of cell growth of certain types of cancer. (15) (research: in vitro / cell cultures). Recent studies have shown a decrease in proliferation and increased apoptosis (cell death) of colorectal (16, 17, 37) and prostate cancer cells. (18, 19, 38)(research: in vitro & in vivo / culture & animals) In cellular culture, a growth inhibitory effect on breast cancer was observed. (25) The growth inhibition was irreversible, with the authors suggesting further investigation of Grape Seed Extract as a possible intervention agent for breast cancer
• Using a research model which demonstrates the formation and progression of carcinogenic chemical induced breast cancer (chemicals as found in tobacco and in the environment), grape seed proanthocyanidins were tested for breast cancer prevention properties. The results showed that grape seed proanthocyanidins offered significant protection against the chemical induced breast cancer. (38)
• Skin cancer cells, both as cellular cultures and as grafted tumor skin growths on mice, were inhibited by grape seed proanthocyanidins. (43). Proanthocyanidins induce apoptosis of the cancer cells, and inhibits cell signalling required for tumor growth.
• Anthocyanidins, the purple pigment in grape skins, demonstrated a chemoprotective effect in colon carcinogenesis in animals. (29) (research: in vivo / animals)
• Grape Skin extract administration to lab animals resulted in a marked reduction of systolic and diastolic pressures. Anti-hypertensive results are attributable to the vasodilation and antioxidant properties of Grape Skin Extract. (5, 41) (research: in vivo / animals) Additionally, Grape Seed Extract has also been shown to have anti-hypertensive action, through improved endothelial function (of the arteries) and blood vessel dilation. In pre-hypertensive subjects, administration of Grape Seed Extract resulted in significant reductions in blood pressure.(23) (research: in vivo / human patients)
• Grape Seed Extract promotes cardiovascular health by protecting the heart and vascular system against free radical damage. The oxidative stress caused by free radicals is associated with cardiovascular pathologies such as congestive heart failure, atherosclerosis,hypertrophy and cardiomyopathy. (11) Grape Seed Extract significantly reduced the amount of oxidized LDL cholesterol in studies performed on animals. Oxidized LDL is typically an indicator of atherosclerosis and other cardiovascular problems. (11, 40) Evidence of Grape Seed Extracts ability to inhibit atherosclerosis development was demonstrated in animal studies. (12) In these studies, the formation of early atherosclerotic lesions was prevented.
• Grape seed extract also plays an important role in vasodilation of the blood vessels, by increasing nitric oxide production. (33) Vasodilation is important for blood pressure control, and for maintenance of a healthy cardiovascular system.
• In the cardiovascular system, the health of the heart, and the cardiac cells which comprise the heart, is of critical importance. Powerful polyphenols in Grape Seed Extracts have been shown to protect cardiac cells from apoptosis (cellular death). Specifically, the Grape Seed Extract polyphenols catechin and proanthocyanidin have been shown to dramatically increase the levels of cellular antioxidant enzymes. The authors indicate that the increase in cellular antioxidant enzymes may play a significant role in protecting the heart against many cardiovascular disorders. (32)(research: in vitro / cellular culture).
• Research indicates that Grape Seed Extract also supports cardiovascular health by: stabilization of the collagen matrix by the cross-linking of collagen fibers, thereby reinforcing vascular connective tissue (3); and stabilization of the capillary walls reducing the permeability of fluids through the capillaries and resulting edema, (13)
Diabetes | High Glucose
• High glucose induced cellular damage, attributable to oxidative stress, is a significant problem among diabetics . Grape Seed Extract has been shown to be effective in protecting the cells against this glucose induced toxicity. (27) (research: in vitro / culture) Grape Seed Extract may help reduce vascular complications of diabetics, caused by advanced glycation end products (AGEs). When glucose binds to a protein in the body, such as vascular collagen, the protein becomes damaged, and starts a chain reaction of reactive oxidative stress. The resulting oxidative stress can further damage the protein, and facilitate disease in the affected structure. Grape Seed Extract reduces vascular collagen damage by helping to inhibit intracellular free radical generation caused by the interaction with AGEs. (28) (research: in vitro / culture)
• Further collagen and glucose incubation studies also substantiated Grape Seed procyanin oligomers as being a potent inhibitor of actual cross-linked AGE formation. (34)(research: in vitro / culture)
Brain and Cognition
• Grape Seed Extract has been shown to protect against age-related lipid oxidation in the central nervous system (including the spinal cord, cerebral cortex and hippocampus regions of the brain) and at the same time increases of the availability of protective antioxidants enzymes (superoxide dismutase, catalase and glutathione peroxidase). (7) Furthermore, Grape Seed Extract also increases the levels of other protective antioxidants in the brain of aged lab animals. (7, 10) (research: in vivo / animals) Additional studies have shown that Grape Seed Extract also inhibits age-related oxidative DNA damage as a result of free radicals in the spinal cord and brain (8), and age-related protein damage in the spinal cord and brain (9). (research: in vivo / animals)
• Grape Seed Extract increases in Acetylcholine concentration in the brain. Acetylcholine is the neurotransmitter important for memory and enhancement of cognition. (7) It also increases memory performance. (10)
• Protective effect of the permeability level of the Blood- Brain-Barrier. The Blood-Brain-Barrier regulates substances exchanged between the brain and the general blood circulation of the body. Under certain pathological conditions, this barrier may become more permeable. Grape Seed Extract helps resist degradation of this barrier. (14) (research: in vitro & in vivo / culture & animals)
• Modulates specific brain proteins which are associated with neuroprotection. Changes in the proteins were in direct opposition to those seen in Alzheimer's disease or in animal models of dementia. (26) (research: in vivo /animals).
• Significantly inhibits the aggregation of amyloid plaque formation, which is believed to be a primary pathological agent in the development of Alzheimer's Disease. Oral administration of grape polyphenols to Alzheimer's model laboratory animals resulted in a substantial reduction in the mental deterioration. The authors of the study suggest that grape polyphenols may offer an important mechanism for either the treatment or prevention of Alzheimer's Disease. (44)(research: in vitro and in vivo / animals).
Sexual & Testosterone Support
• Sexual Support. Nitric oxide production is a required element in the male sexual response. The polyphenol fractions of Grape extracts induce the synthesis of nitric oxide by vascular endothelial cells. This further results in vasorelaxation of the vascular smooth muscle, an important element in establishing an erection. (35)
• The colorful purple pigment in grape skins, called anthocyanidins, inhibit the action of the PDE5 enzyme in smooth muscle. PDE5 degrades the cGMP molecules (important for the enabling a penile erection) in the penis. By inhibiting PDE5, levels of the molecule cGMP are increased, thus enabling the prolonging vasorelaxation and erection. cGMP is the end result of nitric oxide production. Many of the current prescription medicines for erectile dysfunction work on this principal. (36)
• Testosterone Support. For men and woman, Grape Seed Extract can provide beneficial hormonal balancing by inhibiting the conversion of testosterone to estrogen caused by increasing levels of the aromatase enzyme. Grape Seed Extract does this by acting as a potent aromatase enzyme inhibitor.Especially after age 50, men experience an increased activity of the aromatase enzyme converting testosterone to estrogen. Too much estrogen can result in feminizing effects in men.For women, aromatase facilitated conversions into estrogen can be problematic for estrogen dependent breast cancer, This is especially true since aromatase activity os expressed at much higher levels in breast cancer tissue versus normal tissue. (20, 24)
Skin Protection & Enhancement
• Research studies have demonstrated the effectiveness of the polyphenols in Grape Seed extract to promote youthful skin, and enhancing elasticity, through binding with collagen and elastin fibers in the skin. (1) As part of a nutrient complex, grape seed extract was shown to dramatically improved cultured aged skin cells, such that the aged cells characteristics (activity and longevity) became similar to those of young skin cells. (2) (research: in vitro / cell culture) Procyanidol oligomers, a dominant polyphenol found in grape extracts, bind to skin elastin fibers, protecting the elastin in the skin from degradation during inflammatory processes. (3) (research: in vivo / animals)
• Grape seed proanthocyanidns promotes reduction of UVB induced photocarcinogenesis. Likely due to increased antioxidant protection and reduction of tissue fat (4) (research: in vivo / animals)
Weight & Body Toning
• Grape Seed Extract proanthocyanidins significantly decreased the fat in the tissue of animals. (4) Findings also showed that total body mass (lean + fat) remained the same, thereby increasing the ratio of lean body mass. It is proposed that Grape Seed Extract functions by either increasing the breakdown of fat (lipolysis), or decreasing the production of fat.
• Additional research indicates that Grape Seed Extract inhibits the activity of the lipase enzyme, which is responsible for breakdown and absorption of dietary fat. The research paper suggests that Grape Seed Extract may provide a safe and natural method of weight control. (21)
(1) Shi J, et al. Polyphenolics in grape seeds - biochemistry and functionality. J Med Food. 2003 Winter; 6(4) : 291-9.
(2) Lacroix S, et al. Supplementation with a complex of active ingredients improved dermal and epidermal characteristics in skin equivalents generated from fibroblasts from young and aged donors. Biogerontology, 2006 Sept 23.
(3) Tixier JM, et al. Evidence by in vivo and in vitro studies that binding of pycnogenols to elastin affects its rate of degradation by elastases. Biochem Pharmacol. 1984 Dec 15;33(24):3933-9.
(4) Mittal A, et al. Dietary feeding of proanthocyanidins from grape seeds prevents photocarcinogenesis in SKH-1 hairless mice: relationship to decreased fat and lipid peroxidation. Carcinogenesis. 2003 Aug; 24(8): 1379-88
(5) Soares De Moura R., et al. Antihypertensive, vasodilator and antioxidant effects of vinifera grape skin extract. J Pharm Pharmacol 2002 Nov; 54(11): 1515-20
(6) Bagchi D, et al. Free radicals and grape seed proanthocyanidin extract: Importance in human health and disease prevention. Toxicology. 2000 Aug 7; 148(2-3): 187-97
(7) Balu M, et al. Rejuvenation of antioxidant system in central nervous system of aged rats by grape seed extract. Neurosci Lett. 2005 Aug 5; 383(3):295-300
(8) Balu M, et al. Modulatory role of grape seed extract on age-related oxidative DNA damage in central nervous system of rats. Brain Res Bull. 2006 Feb 15;68(6):469-73
(9) Balu,M, et al. Age-related oxidative protein damages in central nervous system of rats: modulatory role of grape seed extract. Int J Dev Neurosci. 2005 Oct;23(6):501-7
(10) Devi, A, et al. Grape seed proanthocyanidin extract (GSPE) and antioxidant defense in the brain of adult rats. Med Sci Monit. 2006 Apr;12(4):BR124-9
(11) Bagchi D, et al. Molecular mechanisms of cardioprotection by a novel grape seed proanthocyanidin extract. Mutat Res 2003 Feb-Mar;523-524:87-97
(12) Auger C, et al. Phenolics from commercialized grape extracts prevent early atherosclerotic lesions in hamsters other than antioxidant effect. J Agric Food Chem. 2004 Aug 11;52(16):5297-302
(13) Robert L, et al. The effect of procyanidolic oligomers on vascular permeability. A study using quantitative morphology. Pathol Biol (Paris) 1990 Jun;38(6):608-16.
(14) Robert AM, et al. Effect of procyanidolic oligomers on the permeability of the blood-brain-barrier. Pathol Biol (Paris). 2001 May;49(4):298-304
(15) Ye X, et al. The cytotoxic effects of a novel IH636 grape seed proanthocyanidin extract on cultured human cancer cells. Mol Cell Biochem, 1999 Jun;196(1-2):99-108
(16) Kaur M, et al. Grape seed extract inhibits in vitro and in vivo growth of human colorectal carcinoma cells. Clin Cancer Res, 2006 Oct 15;12(20 Pt 1):6194-202
(17) Nomoto H, et al. Chemoprevention of colorectal cancer by grape seed proanthocyanidin is accompanied by a decrease in proliferation and increase in apoptosis. Nutr Cancer. 2004;49(1):81-8
(18) Singh RP, et al. Mechanism of action of novel agents for prostate cancer chemoprevention. Endocr Relat Cancer 2006 Sep;13(3):751-78
(19) Tyagi A, et al. Grape seed extract inhibits EGF-induced and constitutively active mitogenic signaling but activates JNK in human prostate carcinoma DU145 cells: possible role in antiproliferation and apoptosis. Oncogene. 2003 Mar 6;22(9):1302-16
(20) Kijima I, et al. Grape seed extract is an aromatas inhibitor and a suppressor of aromatase expression. Cancer Res. 2006 Jun 1;66(11):5960-7
(21) Moreno, DA, et al. Inhibitory effects of grape seed extract on lipases. Nutrition. 2003 Oct; 19(10):876-9.
(22) Ray SD, et al. In vivo protection of dna damage associated apoptotic and necrotic cell deaths during acetaminophen-induced nephrotoxicity, amiodarone-induced lung toxicity and doxorubicin-induced cardiotoxicity by a novel IH636 grape seed proanthocyanidin extract. Res Commun Mol Pathol Pharmacol. 2000;107(1-2):137-66
(23) Siva B, et al. Effect of polyphenolics of grape seeds (GSE) on blood pressure (BP) in patients with metabolic syndrome (MetS). FASEB 2006. San Francisco, CA.
(24) Eng ET, et al. Anti-aromatase chemicals in red wine. Ann N Y Acad Sci. 2002 Jun;963:239-46.
(25) Agarwal, C, et al. A polyphenolic fraction from grape seeds causes irreversible growth inhibition of breast carcinoma MDA-MB468 cells by inhibiting mitogen-activated protein kinases activation and inducing G1 arrest and differentiation. Clin Cancer Res. 2000 Jul;6(7):2921-30.
(26) Kim, H, et al. Proteomics analysis of the actions of grape seed extract in rat brain: technological and biological implications for the study of the actions of psychoactive compounds. Life Sci. 2006 Mar 27;78(18):2060-5.
(27) Fujii H, et al. Protective effect of grape seed polyphenols against high glucose-induced oxidative stress. Biosci Biotechnol Biochem. 2006 Sept;70(9):2104-11
(28) Zhang FL, et al. Selective inhibition by grape seed proanthocyanidin extracts of cell adhesion molecule expression induced by advanced glycation end products in endothelial cells. J Cardiovasc Pharmacol. 2006 Aug;48(2):47-52
(29) Lala G, et al. Anthocyanin-rich extracts inhibit multiple biomarkers of colon cancer in rats. Nutr Cancer. 2006;54(1):84-93
(30) Li WG, et al. Anti-Inflammatory effect and mechanism of proanthocyanidins from grape seeds. Acta Pharmacol Sin. 2001 Dec;22(12):1117-20
(31) Vitseva O, et al. J Cardiovasc Pharmacol. Grape Seed and skin extracts inhibit platelet function and release of reactive oxygen intermediates. 2005 Oct;46(4):445-51
(32) Du, Y, et al. Grape seed polyphenols protect cardiac cells from apoptosis via induction of endogenous antioxidant enzymes. J Agric Food Chem. 2007 Mar 7;55(5):1695-701.
(33) Fitzpatrick DF, et al. Vasodilating procyanidins derived from grape seeds. Ann NY Acad Sci. 2002 May;957:78-89
(34) Urios P, et al. Flavonoids inhibit the formation of the cross-linking AGE pentosidine in collagen incubated with glucose, according to their structure. Eur J Nutr. 2007 Apr;46(3): 139-146.
(35) Wallerath T, et al. A blend of polyphenolic compounds explains the stimulatory effect of red wine on human endothelial NO synthase. Nitric Oxide. 2005 Mar;12(2):97-104
(36) Dell'Agli M, et al. In vitro inhibition of human cGMP-specific phosphodiesterase-5 by polyphenols from red grapes. J Agric Food Chem. 2005 Mar 23;53(6):1960-6
(37) Engelbrecht AM, et al. Proanthocyanidin from grape seeds inactivates the PI3-kinase/PKB pathway and induces apoptosis in a colon cancer cell line. Cancer Lett. 2007 Dec 8;258(1):144-53
(38) Raina K, et al. Oral grape seed extract inhibits prostate tumor growth and progression in TRAMP mice. Cancer Res. 2007 Jun 15;67(12):5976-82.
(39) Siriwardhana N, et al. Precancerous model of human breast epithelial cells induced by NNK for prevention. Breast Cancer Res Treat. 2007 Jul 26.
(40) Sano A, et al. Beneficial effects of grape seed extract on malondialdehyde-modified LDL. J Nutr Sci Vitaminol (Tokyo). 2007 Apr;53(2):17482.
(41) Edirisinghe I, et al. THe mechanism of the endothelium dependent relaxation evoked by a grape seed extract. Clin Sci (Lond). 2007 Oct. 11.
(42) El-Ashmawy IM, et al. Effects of majoram volatile oil and grape seed extract on ethanol toxicity in male rats. Basic Clin Phramacol Toxicol. 2007 Nov;101(5):320-7.
(43) Meeran SM, et al. Proanthocyanidins inhibit mitogenic and survival-signaling in vitro and tumor growth in vivo. Front Biosci. 2008 Jan 1;13-887-97.
(44) Wang J, et al. Grape-derived polyphenolics prevent Abeta oligomerization and attenuate cognitive deterioration in a mouse model of Alzheimer's disease. J Neurosci. 2008 Jun 18;28(25):6388-92.
(45) Pietsch K, et al. Quercetin mediated lifespan extension in Caenorhabditis elegans is modulated by age-1, daf-2, sek-1 and unc-43. Biogerontology. 2009 Oct;10(5):565-78