Grape Seed Extract
NEWS: This superfood is now available in the SANEStore as a convenient whole-food powder so you can more easily enjoy it in smoothies and recipes.
Our Grape Seed Extract Powder is an 95% extract (10:1 ratio) meaning each serving contains an 95% concentration of procyanidins (polyphenols).
Pycnogenol is the trademarked name for the antioxidant from the French Maritime Pine tree. But it is basically the same anthocyanin compound found in grape seed extract. Pycnogenol, like grape seed extract, is a water-soluble flavonoid, or polyphenol, complex with powerful antioxidant properties and may have the ability to reduce blood clotting. As an antioxidant, pycnogenol is thought to possibly offer the following benefits: cardioprotection (reduces risk of atherosclerosis); reduce cancer risk; improve vascular strength (stronger blood vessels); reduce edema (both inflammation and swelling); promote eye health (reduces risk of macular degeneration and cataracts). Research shows that antioxidants like pycnogenol, grape seed, and green tea are generally 10-100 times more powerful than common nutrient antioxidants such as vitamins C and E.
Specific research shows that pycnogenol may be effective in reducing damage to skin caused by ultraviolet radiation from the sun; may be helpful in reducing cancer cell growth and in modulating chronic inflammation as shown in cell culture. In human studies, pycnogenol may prevent excessive platelet aggregation (blood clotting) caused by cigarette smoking and stress. In one study, 100 mg of pycnogenol was as effective as 500 mg of aspirin for reducing platelet aggregation. But pycnogenol does not prolong bleeding time like aspirin though intakes of over 600 mg per day could possibly increase bleeding time.
- May Support a healthy cardiovascular system
- May Reduce menopausal symptoms
- May Improve cognitive function in ADHD
- Helpful for Venous leg ulcers
- May Reduce blood glucose levels
- Alleviating ringing in the ears (tinnitus)
- Excellent free radical scavenger
- May help to Maintain healthy skin
- Reducing cramping in PMS
- Possibly Help manage chronic asthma
- May Improve athletic endurance
- Reducing retinopathy / retina leakage
- Powerful anti-inflammatory benefits
- May Support healthy blood pressure levels
- Reducing gingival bleeding when utilized in chewing gum
- May Improve capillary resistance
- Reducing reactive oxygen species apoptosis
- Protecting & regenerating vitamins C & E
- May Improve male fertility
- May Reduce endometriosis
- Stops mast cells from releasing histamine
- Possible Protective benefits against UV radiation
- Improving circulation problems
- Combating inflammation in lupus
- Reducing platelet aggregation in smokers
- May Improve varicose veins
- Is a mild antihypertensive
- May Improve sexual function in men with erectile dysfunction
- Reducing reduce leg pain, cramps, heaviness, & fluid retention
- Very powerful antioxidant
1. Rosenkranz S, Knirel D, Dietrich H, Flesch M, Erdmann E, Bohm M. Inhibition of the PDGF receptor by red wine flavonoids provides a molecular explanation for the “French paradox”. FASEB J. 2002 Dec;16(14):1958-60.
2. Criqui MH, Ringel BL. Does diet or alcohol explain the French paradox? Lancet. 1994 Dec 24-31;344(8939-8940):1719-23.
3. Burr ML. Explaining the French paradox. JR Soc Health. 1995 Aug;115(4):217-9.
4. Lavayssiere R, Cabee A. MRI in France: the French paradox. J Magn Reson Imaging. 2001 Apr;13(4):528-33.
5. Mar MH, Zeisel SH. Betaine in wine: answer to the French paradox? Med Hypotheses. 1999 Nov;53(5):383-5.
6. De Beer D, Joubert E, Gelderblom W, Manley M. Antioxidant activity of South African red and white cultivar wines: free radical scavenging. J Agric Food Chem. 2003 Feb 12;51(4):902-9.
7. Cui J, Tosaki A, Cordis GA, et al. Cardioprotective abilities of white wine. Ann NY Acad Sci. 2002 May;957:308-16.
8. Bertelli AA, Migliori M, Panichi V, et al. Oxidative stress and inflammatory reaction modulation by white wine. Ann NY Acad Sci. 2002 May;957:295-301.
9. Available at: http://www.plantphysiol.org/cgi/content/full/131/1/129. Accessed April 25, 2005.
10. Available at: http://www.csu.edu.au/research/rpcgwr/research/vitstilb.htm. Accessed April 25, 2005.
11. Ariga T. The antioxidative function, preventive action on disease and utilization of proanthocyanidins. Biofactors. 2004 21(1-4):197-201.
12. Bagchi D, Garg A, Krohn RL, et al. Protective effects of grape seed proanthocyanidins and selected antioxidants against TPA-induced hepatic and brain lipid peroxidation and DNA fragmentation, and peritoneal macrophage activation in mice. Gen Pharmacol. 1998 May;30(5):771-6.
13. Ye X, Krohn RL, Liu W, 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.
14. Deshane J, Chaves L, Sarkikonda KV, et al. Proteomics analysis of rat brain protein modulations by grape seed extract. J Agric Food Chem. 2004 Dec 29;52(26):7872-83.
15. Rababah TM, Hettiarachchy NS, Horax R. Total phenolics and antioxidant activities of fenugreek, green tea, black tea, grape seed, ginger, rosemary, gotu kola and ginkgo extracts, vitamin E and tert-butylhydroquinone. J Agric Food Chem. 2004 Aug 11;52(16):5183-6.
16. Shi J, Yu J, Pohorly JE, Kakuda Y. Polyphenolics in grape seeds–biochemistry and functionality. J Med Food. 2003 Winter;6(4):291-9.
17. Hagerman A, Riedl K, Jones GA, et al. High molecular weight plant polyphenolics (tannins) as biological antioxidants. J Agric Food Chem. 1998 46:1887-92.
18. 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.
19. Choi SM, Lee BM. An alternative mode of action of endocrine-disrupting chemicals and chemoprevention. J Toxicol Environ Health B Crit Rev. 2004 Nov-Dec;7(6):451-63.
20. Delmas D, Jannin B, Latruffe N. Resveratrol: Preventing properties against vascular alterations and aging. Mol Nutr Food Res. 2005 Apr 14.
21. Granieri M, Bellisarii FI, De Caterina R. Group B vitamins as new variables related to the cardiovascular risk. Ital Heart J Suppl. 2005 Jan;6(1):1-16.
22. Hannon-Fletcher MP, Armstrong NC, Scott JM, et al. Determining bioavailability of food folates in a controlled intervention study. Am J Clin Nutr. 2004 Oct;80(4):911-8.
23. Weiswasser JM, Nylen E, Arora S, Wakefield M, Sidawy AN. Syndrome X and diabetes: what is the mystery? Semin Vasc Surg. 2002 Dec;15(4):216-24.
24. Al-Awwadi NA, Araiz C, Bornet A, et al. Extracts enriched in different polyphenolic families normalize increased cardiac NADPH oxidase expression while having differential effects on insulin resistance, hypertension, and cardiac hypertrophy in high-fructose-fed rats. J Agric Food Chem. 2005 Jan 12;53(1):151-7.
25. Al Awwadi NA, Bornet A, Azay J, et al. Red wine polyphenols alone or in association with ethanol prevent hypertension, cardiac hypertrophy, and production of reactive oxygen species in the insulin-resistant fructose-fed rat. J Agric Food Chem. 2004 Sep 8;52(18):5593-7.
26. Kokavec A, Crowe SF. Effect on plasma insulin and plasma glucose of consuming white wine alone after a meal. Alcohol Clin Exp Res. 2003 Nov;27(11):1718-23.
27. Auger C, Teissedre PL, Gérain P, et al. Dietary wine phenolics catechin, quercetin, and resveratrol efficiently protect hyper cholesterolemic hamsters against aortic fatty streak accumulation. J Agric Food Chem. 2005 Mar 23;53 (6):2015-21.
28. Sano T, Oda E, Yamashita T, et al. Anti-thrombotic effect of proanthocyanidin, a purified ingredient of grape seed. Thromb Res. 2005;115(1-2):115-21.
29. Fragopoulou E, Antonopoulou S, Nomikos T, Demopoulos CA. Structure elucidation of phenolic compounds from red/white wine with antiatherogenic properties. Biochim Biophys Acta. 2003 Jun 10;1632(1-3):90-9.
30. Yamakoshi J, Kataoka S, Koga T, Ariga T. Proanthocyanidin-rich extract from grape seeds attenuates the development of aortic atherosclerosis in cholesterol-fed rabbits. Atherosclerosis. 1999 Jan;142(1):139-49.
31. Vinson JA, Mandarano MA, Shuta DL, Bagchi M, Bagchi D. Beneficial effects of a novel IH636 grape seed proanthocyanidin extract and a niacin-bound chromium in a hamster atherosclerosis model. Mol Cell Biochem. 2002 Nov;240(1-2):99- 103.
32. Das S, Cordis GA, Maulik N, Das DK. Pharmacological preconditioning with resveratrol: role of CREB-dependent Bcl-2 signaling via adenosine A3 receptor activation. Am J Physiol Heart Circ Physiol. 2005 Jan;288(1):H328-35.
33. Inoue H, Jiang XF, Katayama T, Osada S, Umesono K, Namura S. Brain protection by resveratrol and fenofibrate against stroke requires peroxisome proliferator-activated receptor alpha in mice. Neurosci Lett. 2003 Dec 11;352(3):203- 6.
34. Weinberger Z, Richter ED. Cellular telephones and effects on the brain: the head as an antenna and brain tissue as a radio receiver. Med Hypotheses. 2002 Dec;59(6):703-5.
35. Available at: http://www.vote.com/vote/1738626/objective1738627.phtml?cat=4075633. Accessed April 27, 2005.
36. Martinez-Burdalo M, Martin A, Anguiano M, Villar R. Comparison of FDTD-calculated specific absorption rate in adults and children when using a mobile phone at 900 and 1800 MHz. Phys Med Biol. 2004 Jan 21;49(2):345-54.
37. Kundi M, Mild K, Hardell L, Mattsson MO. Mobile telephones and cancer–a review of epidemiological evidence. J Toxicol Environ Health B Crit Rev. 2004 Sep-Oct;7(5):351-84.
38. La Regina M, Moros EG, Pickard WF, Straube WL, Baty J, Roti Roti JL. The effect of chronic exposure to 835.62 MHz FDMA or 847.74 MHz CDMA radiofrequency radiation on the incidence of spontaneous tumors in rats. Radiat Res. 2003 Aug;160(2):143-51.
39. Zook BC, Simmens SJ. The effects of 860 MHz radiofrequency radiation on the induction or promotion of brain tumors and other neoplasms in rats. Radiat Res. 2001 Apr;155(4):572-83.
40. Leszczynski D, Joenvaara S, Reivinen J, Kuokka R. Non-thermal activation of the hsp27/p38MAPK stress pathway by mobile phone radiation in human endothelial cells: molecular mechanism for cancer-and blood-brain barrier-related effects. Differentiation. 2002 May;70(2-3):120-9.
41. Zotti-Martelli L, Peccatori M, Scarpato R, Migliore L. Induction of micronuclei in human lymphocytes exposed in vitro to microwave radiation. Mutat Res. 2000 Dec 20;472(1-2):51-8.
42. Irmak MK, Fadillioglu E, Gulec M, Erdogan H, Yagmurca M, Akyol O. Effect of electromagnetic radiation from a cellular telephone on the oxidant and antioxidant levels in rabbits. Cell Biochem Funct. 2002 Dec;20(4):279-83.
43. Stopczyk D, Gnitecki W, Buczynski A, Markuszewski L, Buczynski J. Effect of electromagnetic field produced by mobile phones on the activity of superoxide dismutase (SOD-1) and the level of malonyldialdehyde (MDA)–in vitro study. Med Pr. 2002;53(4):311-4.
44. Ilhan A, Gurel A, Armutcu F, et al. Ginkgo biloba prevents mobile phone-induced oxidative stress in rat brain. Clin Chim Acta. 2004 Feb;340(1-2):153-62.
45. Liu Y, Weng E, Zhang Y, Hong R. Effects of extremely low frequency electromagntic field and its combination with lead on the antioxidant system in mouse. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2002 Aug;20(4):263-5.
46. Nylund R, Leszczynski D. Proteomics analysis of human endothelial cell line EA. hy926 after exposure to GSM 900 radiation. Proteomics. 2004 May;4(5):1359-65.
47. Sharma M, Gupta Y. Chronic treatment with trans resveratrol prevents intracerebroventricular streptozotocin induced cognitive impairment and oxidative stress in rats. Life Sci. 2002 Oct 11;71(21):2489-98.
48. Savaskan E, Olivieri G, Meier F, Seifritz E, Wirz-Justice A, Muller-Spahn F. Red wine ingredient resveratrol protects from beta-amyloid neurotoxicity. Gerontology. 2003 Nov-Dec;49(6):380-3.
49. Roychowdhury S, Wolf G, Keilhoff G, Bagchi D, Horn T. Protection of primary glial cells by grape seed proanthocyanidin extract against nitrosative/oxidative stress. Nitric Oxide. 2001 Apr;5(2):137-49.
50. Jang M, Pezzuto JM. Effects of resveratrol on 12-O-tetradecanoylphorbol-13-acetate-induced oxidative events and gene expression in mouse skin. Cancer Lett. 1998 Dec 11;134(1):81-9.
51. Larsson A, Wilhelmsson U, Pekna M, Pekny M. Increased cell proliferation and neurogenesis in the hippocampal dentate gyrus of old GFAP-/-Vim-/- mice. Neurochem Res. 2004 Nov;29(11):2069-73.
52. Pekny M, Johansson CB, Eliasson C, et al. Abnormal reaction to central nervous system injury in mice lacking glial fibrillary acidic protein and vimentin. J Cell Biol. 1999 May 3;145(3):503-14.
53. Wilhelmsson U, Li L, Pekna M, et al. Absence of glial fibrillary acidic protein and vimentin prevents hypertrophy of astrocytic processes and improves post-traumatic regeneration. J Neurosci. 2004 May 26;24(21):5016-21.
54. Bongcam-Rudloff E. Studies on glial fibrillary acidic protein (GFAP) in human glioma cells in vitro and in vivo. Diss Abstr Int. [c] (201995) 56:445.
55. Tsuji T, Shiozaki A, Kohno R, Yoshizato K, Shimohama S. Proteomic profiling and neurodegeneration in Alzheimer’s disease. Neurochem Res. 2002 Oct;27(10):1245-53.
56. Anga T, Koshiyama I, Fukushima D. Antioxidative properties of procyanidins B-1 and B-3 from azuki beans in aqueous systems. Agric Biol Chem. 1988 52:2717-22.
57. Saito M, Hosoyama M, Ariga T, Kataoka S, Yamaji N. Antiulcer activity of grape seed extract and procyanidins. J Agric Food Chem. 1998 March19;46(4):1460-64.
58. Mittal A, Elmets CA, Katiyar SK. 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.
59. Ishikawa M, Maki K, Tofani I, Kimura K, Kimura M. Grape seed proanthocyanidins extract promotes bone formation in rat’s mandibular condyle. Eur J Oral Sci. 2005 Feb;113(1):47-52.
60. Shimazaki Y, Soh I, Saito T, et al. Influence of detention status on physical disability, mental impairment, and mortality in institutionalized elderly people. J Dent Res. 2001 Jan;80(1):340-5.
61. Center JR, Nguyen TV, Schneider D, Sambrook PN, Eisman JA. Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet. 1999 Mar 13;353(9156):878-82.
62. Mizutani K, Ikeda K, Kawai Y, Yamori Y. Resveratrol stimulates the proliferation and differentiation of osteoblastic MC3T3-E1 cells. Biochem Biophys Res Commun. 1998 Dec 30;253(3):859-63.v 63. Mizutani K, Ikeda K, Kawai Y, Yamori Y. Resveratrol attenuates ovariectomy-induced hyypertension and bone loss in stroke-prone spontaneously hypertensive rats. J Nutr Sci Vitaminol (Tokyo). 2000 Apr;46(2):78-83.
64. Carini M, Aldini G, Bombardelli E, Morazzoni P, Maffei Facino R. UVB-induced hemolysis of rat erythrocytes: protective effect of procyanidins from grape seeds. Life Sci. 2000 Sep 1;67(15):1799-814.
65. Katic M, Kahn CR. The role of insulin and IGF-1 signaling in longevity. Cell Mol Life Sci. 2005 Feb;62(3):320-43.
66. Solari F, Bourbon-Piffaut A, Masse I, Payrastre B, Chan AM, Billaud M. The human tumour suppressor PTEN regulates longevity and dauer formation in Caenohabditis elegans. Oncogene. 2005 Jan 6;24(1):20-7.
67. Preuss HG, Montamarry S, Echard B, Scheckenbach R, Bagchi D. Long-term effects of chromium, grape seed extract, and zinc on various metabolic parameters of rats. Mol Cell Biochem. 2001 Jul;223(1-2):95-102.
68. Preuss HG. Effects of glucose/insulin perturbations on aging and chronic disorders of aging: the evidence. J Am Coll Nutr. 1997 Oct;16(5):397-403.
69. Vogels N, Nijs IM, Westerterp-Plantenga MS. The effect of grape-seed extract on 24 h energy intake in humans. Eur J Clin Nutr. 2004 Apr;58(4):667-73.
70. Pinent M, Blay M, Blade MC, Salvado MJ, Arola L, Ardevol A. Grape seed-derived procyanidins have an antihyperglycemic effect in streptoxotocin-induced diabetic rats and insulinomimetic activity in insulin-sensitive cell lines. Endocrinology. 2004 Nov;145(11):4985-90.
71. Pinent M, Blade MC, Salvado MJ, Arola L, Ardevol A. Intracellular mediators of procyanidin-induced lipolysis in 3T3-L1 adipocytes. J Agric Food Chem. 2005 Jan 26;53(2):262-6.
72. Fan PH, Lou HX. Isolation and structure identification of grape seed polyphenols and its effects on oxidative damage to cellular DNA. Yao Xue Xue Bao. 2004 Nov;39(11):869-75.
73. Carlo G, Schram M. Cell Phones: Invisible Hazards in the Wireless Age: An insider’s Alarming Discoveries about Cancer and Genetic Damage. New York: Carroll & Graf Publishers; 2001.
74. Trosic I, Busljeta I, Kasuba V, Rozgaj R. Micronucleus induction after whole-body microwave irradiation of rats. Mutat Res. 2002 Nov 26;521(1-2):73-9.
75. Goswami PC, Albee LD, Parsian AJ, et al. Proto-oncogene mRNA levls and activities of multiple transcription factors in C3H 10T 1/2 murine embryonic fibroblasts exposed to 835.62 and 847.74 MHz cellular phone communication frequency radiation. Radiat Res. 1999 Mar;151(3):300-9.
76. Bagchi, Debasis; Sen, Chandan K; Ray, Sidhartha D; Das, Dipak K; Bagchi, Manashi; Preuss, Harry G; Vinson, Joe A (2003). “Molecular mechanisms of cardioprotection by a novel grape seed proanthocyanidin extract”. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 523-524: 87–97. doi:10.1016/S0027-5107(02)00324-X. PMID 12628506.
77. Vitseva, Olga; Varghese, Sonia; Chakrabarti, Subrata; Folts, John D; Freedman, Jane E (2005). “Grape Seed and Skin Extracts Inhibit Platelet Function and Release of Reactive Oxygen Intermediates”. Journal of Cardiovascular Pharmacology 46 (4): 445–51. doi:10.1097/01.fjc.0000176727.67066.1c. PMID 16160595.
78. Kundu, Joydeb Kumar; Surh, Young-Joon (2008). “Cancer chemopreventive and therapeutic potential of resveratrol: Mechanistic perspectives”. Cancer Letters 269 (2): 243–61. doi:10.1016/j.canlet.2008.03.057. PMID 18550275.
79. Gao, N.; Budhraja, A.; Cheng, S.; Yao, H.; Zhang, Z.; Shi, X. (2009). “Induction of Apoptosis in Human Leukemia Cells by Grape Seed Extract Occurs via Activation of c-Jun NH2-Terminal Kinase”. Clinical Cancer Research 15 (1): 140–9. doi:10.1158/1078-0432.CCR-08-1447. PMC 2760842. PMID 19118041. Lay summary – BBC News (31 December 2008).
80. Khanna, Savita; Venojarvi, Mika; Roy, Sashwati; Sharma, Nidhi; Trikha, Prashant; Bagchi, Debasis; Bagchi, Manashi; Sen, Chandan K (2002). “Dermal wound healing properties of redox-active grape seed proanthocyanidins”. Free Radical Biology and Medicine 33 (8): 1089–96. doi:10.1016/S0891-5849(02)00999-1. PMID 12374620.
81. Smullen, J.; Koutsou, G.A.; Foster, H.A.; Zumbé, A.; Storey, D.M. (2007). “The Antibacterial Activity of Plant Extracts Containing Polyphenols against Streptococcus mutans”. Caries Research 41 (5): 342–9. doi:10.1159/000104791. PMID 17713333.
82. Yahara, N; Tofani, I; Maki, K; Kojima, K; Kojima, Y; Kimura, M (2005). “Mechanical assessment of effects of grape seed proanthocyanidins extract on tibial bone diaphysis in rats”. Journal of musculoskeletal & neuronal interactions 5 (2): 162–9. PMID 15951633.
83. Katiyar, Santosh K. (2008). “Grape seed proanthocyanidines and skin cancer prevention: Inhibition of oxidative stress and protection of immune system”. Molecular Nutrition & Food Research. 52 Suppl 1: S71–6. doi:10.1002/mnfr.200700198. PMC 2562900. PMID 18384090.
84. Baliga, Manjeshwar S.; Katiyar, Santosh K. (2006). “Chemoprevention of photocarcinogenesis by selected dietary botanicals”. Photochemical & Photobiological Sciences 5 (2): 243–53. doi:10.1039/b505311k. PMID 16465310.
85. Su, X; d’Souza, DH (2011). “Grape seed extract for control of human enteric viruses”. Applied and environmental microbiology 77 (12): 3982–7. doi:10.1128/AEM.00193-11. PMC 3131668. PMID 21498749.
86. Nair, Madhavan P; Kandaswami, Chithan; Mahajan, Supriya; Nair, Harikrishna N; Chawda, RAM; Shanahan, Thomas; Schwartz, Stanley A (2002). “Grape seed extract proanthocyanidins downregulate HIV- 1 entry coreceptors, CCR2b, CCR3 and CCR5 gene expression by normal peripheral blood mononuclear cells”. Biological Research 35 (3–4): 421–31. doi:10.4067/S0716-97602002000300016. PMID 12462994.
87. Pan, Xinjuan; Dai, Yujie; Li, Xing; Niu, Nannan; Li, Wenjie; Liu, Fangli; Zhao, Yang; Yu, Zengli (2011). “Inhibition of arsenic induced-rat liver injury by grape seed exact through suppression of NADPH oxidase and TGF-β/Smad activation”. Toxicology and Applied Pharmacology 254 (3): 323–31. doi:10.1016/j.taap.2011.04.022. PMID 21605584.
88. University of Maryland Medical Center – Grape Seed.
89. Search results for grape seed extracts, ClinicalTrials.gov, a service of the US National Institutes of Health.
90. Mellen, Philip B.; Daniel, Kurt R.; Brosnihan, K. Bridget; Hansen, Kim J.; Herrington, David M. (2010). “Effect of Muscadine Grape Seed Supplementation on Vascular Function in Subjects with or at Risk for Cardiovascular Disease: A Randomized Crossover Trial”. Journal of the American College of Nutrition 29 (5): 469–75. PMC 3313487. PMID 21504973.
91 Feringa, Harm H.H.; Laskey, Dayne A.; Dickson, Justine E.; Coleman, Craig I. (2011). “The Effect of Grape Seed Extract on Cardiovascular Risk Markers: A Meta-Analysis of Randomized Controlled Trials”. Journal of the American Dietetic Association 111 (8): 1173–81. doi:10.1016/j.jada.2011.05.015. PMID 21802563.
92. Grape Seed Extract, Herbs at a Glance, US National Center for Complementary and Alternative Medicine.
93. Brooker, S; Martin, S; Pearson, A; Bagchi, D; Earl, J; Gothard, L; Hall, E; Porter, L et al. (2006). “Double-blind, placebo-controlled, randomised phase II trial of IH636 grape seed proanthocyanidin extract (GSPE) in patients with radiation-induced breast induration”. Radiotherapy and Oncology 79 (1): 45–51. doi:10.1016/j.radonc.2006.02.008. PMID 16546280.
94. Shanmuganayagam, Dhanansayan; Beahm, Mark R.; Osman, Hashim E.; Krueger, Christian G.; Reed, Jess D.; Folts, John D. (2002). “Grape Seed and Grape Skin Extracts Elicit a Greater Antiplatelet Effect When Used in Combination than When Used Individually in Dogs and Humans”. The Journal of Nutrition 132 (12): 3592–8. PMID 12468593.
95. Kijima, I.; Phung, S; Hur, G; Kwok, SL; Chen, S (2006). “Grape Seed Extract is an Aromatase Inhibitor and a Suppressor of Aromatase Expression”. Cancer Research 66 (11): 5960–7. doi:10.1158/0008-5472.CAN-06-0053. PMID 16740737.
96.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.
97. 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.
98. van de Wiel A, van Golde PH, Hart HC. Blessings of the grape. Eur J Intern Med. 2001 Dec;12(6):484-9.
99. 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.
100. Sovak M. Grape extract, resveratrol, and its analogs: a review. J Med Food. 2001;4(2):93-105.
101. Bhat KPL, Kosmeder JW, Pezzuto JM. Biological effects of resveratrol. Antioxid Redox Signal. 2001 Dec;3(6):1041-64.
102. Bradamante S, Barenghi L, Villa A. Cardiovascular protective effects of resveratrol. Cardiovasc Drug Rev. 2004;22(3):169-88.
103. 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.
104. 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.
105. 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.
106. 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.
107. 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.
108. 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.
109. 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.
110. 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.
111. 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.
112. 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.
113. 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.
114. 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.
115. 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.
116. Folts JD. Potential health benefits from the flavonoids in grape products on vascular disease. Adv Exp Med Biol. 2002;505:95-111.
117. Caimi G, Carollo C, Lo PR. Wine and endothelial function. Drugs Exp Clin Res. 2003;29(5-6):235-42.
118. 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.
119. 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.
120. 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.
121. 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.
122. 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.
123. 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.
124. 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.
125. 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.
126. 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.
127. 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.
128. 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.
129. 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.
130. 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.
131. 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.
132. 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.
133. 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.
134. 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.
135. 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.
136. Ruf JC. Alcohol, wine and platelet function. Biol Res. 2004;37(2):209-15.
137. Renaud SC, Ruf JC. Effects of alcohol on platelet functions. Clin Chim Acta. 1996 Mar 15;246(1-2):77-89.
138. Ruf JC. Wine and polyphenols related to platelet aggregation and atherothrombosis. Drugs Exp Clin Res. 1999;25(2-3):125-31.
139. 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.
140. Mezzano D. Distinctive effects of red wine and diet on haemostatic cardiovascular risk factors. Biol Res. 2004;37(2):217-24.
141. 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.
142. 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.
143. 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.
144. 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.
145. 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.
146. 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.
147. 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.
148. 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.
149. 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.
150. Available at:http://www.pdrhealth.com/drug_info/nmdrugprofiles/herbaldrugs/101305.shtml. Accessed June 27, 2007.
151. 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.
152. 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.
153. 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.
154. 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.
155 Brooker S, Martin S, Pearson A, et al. Double-blind, placebo-controlled, randomised phase II trial of IH636 grape seed proanthocyanidin extract (GSPE) in patients with radiation-induced breast induration. Radiotherapy and Oncology. 2006;79(1):45-51.
156. Clouatre DL, Kandaswami C. Grape seed extract. In: Coates P, Blackman M, Cragg G, et al., eds. Encyclopedia of Dietary Supplements. New York, NY: Marcel Dekker; 2005:309-325.
157. Grape. Natural Medicines Comprehensive Database Web site. Accessed on March 13, 2007.
158. Grape seed (Vitis vinifera, Vitis coignetiae). Natural Standard Database Web site. Accessed on March 13, 2007.
159. Agarwal C, Sharma Y, Agarwal R. Anticarcinogenic effect of a polyphenolic fraction isolated from grape seeds in human prostate carcinoma DU145 cells: modulation of mitogenic signaling and cell-cycle regulators and induction of G1 arrest and apoptosis. Mol Carcinog 2000;28:129-38.
160. Anon. OPCs (Oligomeric Proanthocyanidins). The Natural Pharmacist 2000.http://www.tnp.com/substance.asp?ID=181. (Accessed 3 June 2000).
161. Bagchi D, Bagchi M, Stohs SJ, et al. Cellular protection with proanthocyanidins derived from grape seeds. Ann N Y Acad Sci 2002;957:260-70.
162. Barona J, Aristizabal JC, Blesso CN, et al. Grape polyphenols reduce blood pressure and increase flow-mediated vasodilation in men with metabolic syndrome. J Nutr 2012;142:1626-32.
163. Bernstein DI, Bernstein CK, Deng C, et al. Evaluation of the clinical efficacy and safety of grapeseed extract in the treatment of fall seasonal allergic rhinitis: a pilot study. Ann Allergy Asthma Immunol 2002;88:272-8.
164. BIBRA working group. Anthocyanins. Toxicity profile. BIBRA Toxicol Int 1991;6.
165. Bombardelli E, Morazzoni P. Vitis vinifera L. Fitoterapia 1995;LXVI:291-317.
166. Chevallier A. The Encyclopedia of Medicinal Plants. London, UK: Dorling Kindersley, Ltd., 1996.
167. Chisholm A, Mann J, Skeaff M, et al. A diet rich in walnuts favourably influences plasma fatty acid profile in moderately hyperlipidaemic subjects. Eur J Clin Nutr 1998;52:12-6.
168. Covington TR, et al. Handbook of Nonprescription Drugs. 11th ed. Washington, DC: American Pharmaceutical Association, 1996.
169. Electronic Code of Federal Regulations. Title 21. Part 182 — Substances Generally Recognized As Safe. Available at:http://ecfr.gpoaccess.gov/cgi/t/text/text-idx?c=ecfr&sid=786bafc6f6343634fbf79fcdca7061e1&rgn=div5&view= text&node=21:220.127.116.11.13&idno=21
170. Freedman JE, Parker C, Li L, et al. Select flavonoids and whole juice from purple grapes inhibit platelet function and enhance nitric oxide release. Circulation 2001;103:2792-8.
171. Kiesewetter H, Koscielny J, Kalus U, et al. Efficacy of orally administered extract of red vine leaf AS 195 (folia vitis viniferae) in chronic venous insufficiency (stages I-II). A randomized, double-blind, placebo-controlled trial. Arzneimittelforschung 2000;50:109-17.
172. Meyer AS, Yi OS, Pearson DA, et al. Inhibition of human low-density lipoprotein oxidation in relation to composition of phenolic antioxidants in grapes (Vitis vinifera). J Agric Food Chem 1997;45:1638-43.
173. 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;23:385-89.
174. Pataki T, Bak I, Kovacs P, et al. Grape seed proanthocyanidins improved cardiac recovery during reperfusion after ischemia in isolated rat hearts. Am J Clin Nutr 2002;75:894-9.
175. Peirce A. The American Pharmaceutical Association Practical Guide to Natural Medicines. New York, NY: William Morrow and Co., 1999.
175. Stein JH, Keevil JG, Wiebe DA, et al. Purple grape juice improves endothelial function and reduces the susceptibility of LDL cholesterol to oxidation in patients with coronary artery disease. Circulation 1999;100:1050-5.
177. Vaswani SK, Hamilton RG, Carey RN, et al. Anaphylaxis recurrent urticaria and angioedema from grape hypersensitivity. J Allergy Clin Immunol 1998;101:S31.
178. Ward NC, Hodgson JM, Croft KD, et al. The combination of vitamin C and grape-seed polyphenols increases blood pressure: a randomized, double-blind, placebo-controlled trial. J Hypertens 2005;23:427-34.
179. Xiao Dong S, Zhi Ping Z, Zhong Xiao W, et al. Possible enhancement of the first-pass metabolism of phenacetin by ingestion of grape juice in Chinese subjects. Br J Clin Pharmacol 1999;48:638-40.
180. Wilson D, Evans M, Guthrie N et al. A randomized, double-blind, placebo-controlled exploratory study to evaluate the potential of pycnogenol for improving allergic rhinitis symptoms. Phytother Res 2010;24:1115-9.
181. Belcaro G, Cesarone MR, Ricci A, et al. Control of edema in hypertensive subjects treated with calcium antagonist (nifedipine) or angiotensin-converting enzyme inhibitors with pycnogenol. Clin Appl Thromb Hemost 2006;12:440-4.
182. Vinciguerra G, Belcaro G, Cesarone MR, et al. Cramps and muscular pain: prevention with Pyconogenol in normal subjects, venous patients, athletes, claudicants and in diabetic microangiopathy. Angiology 2006;57:331-9.
183. Cesarone MR, Belcaro G, Rohdewald P, et al. Improvement of diabetic microangiopathy with Pycnogenol: A prospective, controlled study. Angiology 2006;57:431-6.
184. Liu X, Wei J, Tan F, et al. Antidiabetic effect of Pycnogenol French maritime pine bark extract in patients with diabetes type II. Life Sci 2004;75:2505-13.
185. Liu X, Zhou HJ, Rohdewald P. French maritime pine bark extract pycnogenol dose-dependently lowers glucose in type 2 diabetic patients (letter). Diabetes Care 2004;27:839.
186. Kohama T, Suzuki N, Ohno S, Inoue M. Analgesic efficacy of French maritime pine bark extract in dysmenorrhea: an open clinical trial. J Reprod Med 2004;49:828-32.
187. Kohama T, Inoue M. Pycnogenol alleviates pain associated with pregnancy. Phytother Res 2006;20:232-4.
188. Blazso G, Gabor M, Schonlau F, Rohdewald P. Pycnogenol accelerates wound healing and reduces scar formation. Phytother Res 2004;18:579-81.
189. Yang HM, Liao MF, Zhu SY, et al. A randomised, double-blind, placebo-controlled trial on the effect of Pycnogenol on the climacteric syndrome in premenopausal women. Acta Obstet Gynecol Scand 2007;86:978-85.