Life Extension Magazine September 2007
Protecting Cardiovascular Health with Whole Grape Extract
By Julius G. Goepp, MD
By Julius G. Goepp, MD
Keeping Platelets Slippery
The formation of abnormal arterial blood clots (thrombosis) is a primary cause of heart attack and stroke. Thrombosis is the pathological clumping together of platelets, the tiny cell fragments in blood normally responsible for healthy blood coagulation after injury. There are many chemical triggers that cause platelets to clump, or aggregate, and laboratory studies have demonstrated how the polyphenols found in red grape products (including grape seed extracts) act powerfully to regulate platelet aggregation.37-40
In humans, strong support for the health-promoting effect of polyphenols from red grapes comes both from studies of large populations and from clinical trials.41 People who live in cultures where moderate red wine is consumed regularly have lower rates of illness and death from coronary heart disease, and that effect has been tracked in part to decreased platelet activity.42,43
Researchers in Chile determined the coagulation-related risk reduction more specifically when they studied two groups of 21 healthy young men given a “Mediterranean diet” or a high-fat diet for 90 days.44,45 For one month in the middle of that period, the men drank 8 ounces of red wine daily, and various blood factors associated with clotting were determined throughout the study. Regardless of whether the men ate the healthful Mediterranean diet or the riskier high-fat diet, when red wine was added to the mix, clotting factors decreased substantially.
Intriguing research supports the role of red grapes in averting aberrant platelet aggregation and coagulation. In 2002, Italian scientists showed that when they gave 20 healthy subjects 10 ounces per day of either red or white wine (both with the same alcohol concentration), the red wine-drinking subjects had significantly lower platelet aggregation after a stimulus than did the white wine-drinkers.46
Not to be outdone, researchers in France’s Bordeaux region showed that it didn’t even have to be red wine, so long as the source of the beverage was the whole grape.47 In a study that can only be described as sophisticated, these scientists randomly assigned healthy volunteers to drink either one ounce of vodka (no polyphenols) or Armagnac, a distilled brandy derived from polyphenol-rich grapes.48 The researchers found that after 14 days, platelet aggregation in the Armagnac group was reduced by 31%, compared to only 11% in the vodka group.47 Equally importantly, two weeks after the alcohol consumption stopped, the vodka drinkers experienced a “rebound” increase of platelet aggregation, which was not seen in the Armagnac group. These results point to the importance of grape polyphenols as the source of the benefits.
A study from China further illustrated the “blessings of the grape.”49 Scientists investigated the effects of both red wine and resveratrol, one of the main components of grape extracts, on aggregation of platelets from healthy human volunteers. When they treated the platelets with resveratrol they found that aggregation was inhibited in direct proportion to the amount of resveratrol used. When they conducted the same experiment using rabbits with elevated serum cholesterol and increased platelet aggregation, the researchers were again able to demonstrate potent reduction using grape extract-derived resveratrol. These results provide strong evidence that red grape polyphenols such as resveratrol produce their cardioprotective effects at least in part by inhibiting platelet aggregation.
Some skeptics have suggested that the effects of extracts are only seen in the laboratory, where they can be directly applied to the cells being studied.50 It has been convincingly demonstrated, however, that the grape extract components are in fact absorbed from the human intestinal tract in large enough quantities to cause reduction in risk of atherosclerosis.51 This effect can be enhanced when the extracts are high in the polyphenols extracted from grape seeds, and contain a large proportion of the short-chain polyphenols known as oligomers.52-54
Supplementing with Grape Seed Extract
Grape seed extract supplements provide a readily-available, convenient way to capture the abundant cardiovascular benefits of the grape. The Physician’s Desk Reference reports that grape seed extract is safe, with no known toxicity, adverse reactions, or drug interactions.55 Many health practitioners recommend supplementing with 100-600 mg of grape seed extract daily in divided doses.
As cardiovascular disease claims more lives than any other disease in America today, grape seed extract may offer much-needed protection. Grape polyphenols fight several key triggers of deadly cardiovascular disease—lipid peroxidation, endothelial dysfunction, and aberrant platelet aggregation. Further, grape polyphenols show promise in protecting against the effects of oxidative stress and poor dietary choices. By incorporating grape seed extract in your daily wellness program, you can help ensure optimal protection for your cardiovascular system.
1. Soleas GJ, Diamandis EP, Goldberg DM. Wine as a biological fluid: history, production, and role in disease prevention. J Clin Lab Anal. 1997;11(5):287-313.
2. Bavaresco L, Fregoni C, Cantu E, Trevisan M. Stilbene compounds: from the grapevine to wine. Drugs Exp Clin Res. 1999;25(2-3):57-63.
3. van de Wiel A, van Golde PH, Hart HC. Blessings of the grape. Eur J Intern Med. 2001 Dec;12(6):484-9.
4. van de Wiel A. Nutrition and health—favorable effect of wine and wine flavonoids on cardiovascular diseases. Ned Tijdschr Geneeskd. 2002 Dec 21;146(51):2466-9.
5. Sovak M. Grape extract, resveratrol, and its analogs: a review. J Med Food. 2001;4(2):93-105.
6. Bhat KPL, Kosmeder JW, Pezzuto JM. Biological effects of resveratrol. Antioxid Redox Signal. 2001 Dec;3(6):1041-64.
7. Bradamante S, Barenghi L, Villa A. Cardiovascular protective effects of resveratrol. Cardiovasc Drug Rev. 2004;22(3):169-88.
8. Bagchi D, Bagchi M, Stohs SJ, 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.
9. Kalkan Yildirim H, Delen Akçay Y, Güvenç U, Yildirim Sözmen E. Protection capacity against low-density lipoprotein oxidation and antioxidant potential of some organic and non-organic wines. Int J Food Sci Nutr. 2004 Aug;55(5):351-62.
10. Natella F, Belelli F, Gentili V, Ursini F, Scaccini C. Grape seed proanthocyanidins prevent plasma postprandial oxidative stress in humans. J Agric Food Chem. 2002 Dec 18;50(26):7720-5.
11. Nuttall SL, Kendall MJ, Bombardelli E, Morazzoni P. An evaluation of the antioxidant activity of a standardized grape seed extract, Leucoselect. J Clin Pharm Ther. 1998 Oct;23(5):385-9.
12. Aviram M, Lavy A, Fuhrman B. Plasma lipid peroxidation: inhibited by drinking red wine but stimulated by white wine. Harefuah.1994 Dec 15;127(12):517-20, 575-6.
13. bu-Amsha CR, Burke V, Mori TA, et al. Red wine polyphenols, in the absence of alcohol, reduce lipid peroxidative stress in smoking subjects. Free Radic Biol Med. 2001 Mar 15;30(6):636-42.
14. Avellone G, Di G, V, Campisi D, et al. Effects of moderate Sicilian red wine consumption on inflammatory biomarkers of atherosclerosis. Eur J Clin Nutr. 2006 Jan;60(1):41-7.
15. Guarda E, Godoy I, Foncea R, et al. Red wine reduces oxidative stress in patients with acute coronary syndrome. Int J Cardiol. 2005 Sep 15;104(1):35-8.
16. Marfella R, Cacciapuoti F, Siniscalchi M, et al. Effect of moderate red wine intake on cardiac prognosis after recent acute myocardial infarction of subjects with Type 2 diabetes mellitus. Diabet Med. 2006 Sep;23(9):974-81.
17. Tsang C, Higgins S, Duthie GG, et al. The influence of moderate red wine consumption on antioxidant status and indices of oxidative stress associated with CHD in healthy volunteers. Br J Nutr.2005 Feb;93(2):233-40.
18. Williams MJ, Sutherland WH, Whelan AP, McCormick MP, de Jong SA. Acute effect of drinking red and white wines on circulating levels of inflammation-sensitive molecules in men with coronary artery disease. Metabolism. 2004 Mar;53(3):318-23.
19. Young JF, Dragsted LO, Daneshvar B, et al. The effect of grape-skin extract on oxidative status. Br J Nutr. 2000 Oct;84(4):505-13.
20. Coimbra SR, Lage SH, Brandizzi L, Yoshida V, da Luz PL. The action of red wine and purple grape juice on vascular reactivity is independent of plasma lipids in hypercholesterolemic patients. Braz J Med Biol Res. 2005 Sep;38(9):1339-47.
21. Folts JD. Potential health benefits from the flavonoids in grape products on vascular disease. Adv Exp Med Biol. 2002;505:95-111.
22. Caimi G, Carollo C, Lo PR. Wine and endothelial function. Drugs Exp Clin Res. 2003;29(5-6):235-42.
23. Corder R, Warburton RC, Khan NQ, et al. The procyanidin-induced pseudo laminar shear stress response: a new concept for the reversal of endothelial dysfunction. Clin Sci (Lond). 2004 Nov;107(5):513-7.
24. Karatzi K, Papamichael C, Karatzis E, et al. Acute smoking induces endothelial dysfunction in healthy smokers. Is this reversible by red wine’s antioxidant constituents? J Am Coll Nutr. 2007 Feb;26(1):10-5.
25. Cuevas AM, Guasch V, Castillo O, et al. A high-fat diet induces and red wine counteracts endothelial dysfunction in human volunteers. Lipids. 2000 Feb;35(2):143-8.
26. Agewall S, Wright S, Doughty RN, et al. Does a glass of red wine improve endothelial function? Eur Heart J. 2000 Jan;21(1):74-8.
27. Lekakis J, Rallidis LS, Andreadou I, et al. Polyphenolic compounds from red grapes acutely improve endothelial function in patients with coronary heart disease. Eur J Cardiovasc Prev Rehabil. 2005 Dec;12(6):596-600.
28. Estruch R, Sacanella E, Badia E, et al. Different effects of red wine and gin consumption on inflammatory biomarkers of atherosclerosis: a prospective randomized crossover trial. Effects of wine on inflammatory markers. Atherosclerosis. 2004 Jul;175(1):117-23.
29. Badia E, Sacanella E, Fernandez-Sola J, et al. Decreased tumor necrosis factor-induced adhesion of human monocytes to endothelial cells after moderate alcohol consumption. Am J Clin Nutr. 2004 Jul;80(1):225-30.
30. Boban M, Modun D, Music I, et al. Red wine induced modulation of vascular function: separating the role of polyphenols, ethanol, and urates. J Cardiovasc Pharmacol. 2006 May;47(5):695-701.
31. Diebolt M, Bucher B, Andriantsitohaina R. Wine polyphenols decrease blood pressure, improve NO vasodilatation, and induce gene expression. Hypertension. 2001 Aug;38(2):159-65.
32. Leighton F, Cuevas A, Guasch V, et al. Plasma polyphenols and antioxidants, oxidative DNA damage and endothelial function in a diet and wine intervention study in humans. Drugs Exp Clin Res. 1999;25(2-3):133-41.
33. Naissides M, Pal S, Mamo JC, James AP, Dhaliwal S. The effect of chronic consumption of red wine polyphenols on vascular function in postmenopausal women. Eur J Clin Nutr. 2006 Jun;60(6):740-5.
34. Rakici O, Kiziltepe U, Coskun B, Aslamaci S, Akar F. Effects of resveratrol on vascular tone and endothelial function of human saphenous vein and internal mammary artery. Int J Cardiol. 2005 Nov 2;105(2):209-15.
35. Whelan AP, Sutherland WH, McCormick MP, et al. Effects of white and red wine on endothelial function in subjects with coronary artery disease. Intern Med J. 2004 May;34(5):224-8.
36. Kar P, Laight D, Shaw KM, Cummings MH. Flavonoid-rich grapeseed extracts: a new approach in high cardiovascular risk patients? Int J Clin Pract. 2006 Nov;60(11):1484-92.
37. Dobrydneva Y, Williams RL, Blackmore PF. trans-Resveratrol inhibits calcium influx in thrombin-stimulated human platelets. Br J Pharmacol. 1999 Sep;128(1):149-57.
38. Kaneider NC, Mosheimer B, Reinisch N, Patsch JR, Wiedermann CJ. Inhibition of thrombin-induced signaling by resveratrol and quercetin: effects on adenosine nucleotide metabolism in endothelial cells and platelet-neutrophil interactions. Thromb Res. 2004;114(3):185-94.
39. Ruf JC, Berger JL, Renaud S. Platelet rebound effect of alcohol withdrawal and wine drinking in rats. Relation to tannins and lipid peroxidation. Arterioscler Thromb Vasc Biol. 1995 Jan;15(1):140-4.
40. Xia J, Allenbrand B, Sun GY. Dietary supplementation of grape polyphenols and chronic ethanol administration on LDL oxidation and platelet function in rats. Life Sci. 1998;63(5):383-90.
41. Ruf JC. Alcohol, wine and platelet function. Biol Res. 2004;37(2):209-15.
42. Renaud SC, Ruf JC. Effects of alcohol on platelet functions. Clin Chim Acta. 1996 Mar 15;246(1-2):77-89.
43. Ruf JC. Wine and polyphenols related to platelet aggregation and atherothrombosis. Drugs Exp Clin Res. 1999;25(2-3):125-31.
44. Mezzano D, Leighton F. Haemostatic cardiovascular risk factors: differential effects of red wine and diet on healthy young. Pathophysiol Haemost Thromb. 2003 Sep 20;33(5-6):472-8.
45. Mezzano D. Distinctive effects of red wine and diet on haemostatic cardiovascular risk factors. Biol Res. 2004;37(2):217-24.
46. Pignatelli P, Lenti L, Pulcinelli FM, et al. Red and white wine differently affect collagen-induced platelet aggregation. Pathophysiol Haemost Thromb. 2002 Sep;32(5-6):356-8.
47. Umar A, Depont F, Jacquet A, et al. Effects of armagnac or vodka on platelet aggregation in healthy volunteers: a randomized controlled clinical trial. Thromb Res. 2005;115(1-2):31-7.
48. Umar A, Guerin V, Renard M, et al. Effects of armagnac extracts on human platelet function in vitro and on rat arteriovenous shunt thrombosis in vivo. Thromb Res. 2003 May 1;110(2-3):135-40.
49. Wang Z, Huang Y, Zou J, et al. Effects of red wine and wine polyphenol resveratrol on platelet aggregation in vivo and in vitro. Int J Mol Med. 2002 Jan;9(1):77-9.
50. Goldberg DM, Yan J, Soleas GJ. Absorption of three wine-related polyphenols in three different matrices by healthy subjects. Clin Biochem. 2003 Feb; 36(1):79-87.
51. Pace-Asciak CR, Rounova O, Hahn SE, Diamandis EP, Goldberg DM. Wines and grape juices as modulators of platelet aggregation in healthy human subjects. Clin Chim Acta. 1996 Mar 15;246(1-2):163-82.
52. Aruoma OI, Sun B, Fujii H, et al. Low molecular proanthocyanidin dietary biofactor Oligonol: Its modulation of oxidative stress, bioefficacy, neuroprotection, food application and chemoprevention potentials. Biofactors. 2006;27(1-4):245-65.
53. Carini M, Stefani R, Aldini G, Ozioli M, Facino RM. Procyanidins from Vitis vinifera seeds inhibit the respiratory burst of activated human neutrophils and lysosomal enzyme release. Planta Med. 2001 Nov;67(8):714-7.
54. Ward NC, Croft KD, Puddey IB, Hodgson JM. Supplementation with grape seed polyphenols results in increased urinary excretion of 3-hydroxyphenylpropionic Acid, an important metabolite of proanthocyanidins in humans. J Agric Food Chem. 2004 Aug 25;52(17):5545-9.
55. Available at: http://www.pdrhealth.com/drug_info/nmdrugprofiles/herbaldrugs/101305.shtml. Accessed June 27, 2007.
56. Yu H, Wang SE, Zhao C, Xu G. Study of anti-atherosclerosic effect of grape seed extract and its mechanism. Wei Sheng Yan.Jiu. 2002 Aug;31(4):263-5.
57. Zern TL, West KL, Fernandez ML. Grape polyphenols decrease plasma triglycerides and cholesterol accumulation in the aorta of ovariectomized guinea pigs. J Nutr. 2003 Jul;133(7):2268-72.
58. Fuhrman B, Volkova N, Coleman R, Aviram M. Grape powder polyphenols attenuate atherosclerosis development in apolipoprotein E deficient (E0) mice and reduce macrophage atherogenicity. J Nutr . 2005 Apr;135(4):722-8.
59. Bagchi D, Sen CK, Ray SD, et al. Molecular mechanisms of cardioprotection by a novel grape seed proanthocyanidin extract. Mutat Res. 2003 Feb;523-524:87-97.