Life Extension Skin Care Sale

Life Extension Magazine

LE Magazine July 2005

Broad-Spectrum Effects of Grape Seed Extract

By Terri Mitchell

Take 20 Years Off Your Brain

Ever wish you could think of things, and remember like you used to? The brain ages just like the rest of you. The important thing is to counteract the wear and tear as much as possible.

There is good news on this front. For the first time in history, researchers have proven that a supplement reverses brain aging at the most basic level: proteins. This exciting research is like discovering what is wrong with each brick of an aging house.

What these researchers found is that age not only causes proteins to be lost, but also causes undesirable proteins to be gained. The age-related increases are just as detrimental as age-related decreases.

This research from the University of Alabama shows that grape seed extract normalizes 13 different brain proteins back to youthful levels.14 Undesirable proteins that impede the brain’s ability to make new cells are reduced.14,51 (New brain cells are made in certain areas of the brain throughout the human life span. For more information, see “Reinventing the Brain,” Life Extension, August 2000.) A protein that makes a type of scar tissue in the brain is also reduced, potentially helping the brain recover from injuries like stroke.14,52,53 The same protein also shows up in certain types of brain tumors and in Alzheimer’s disease.54,55 Grape seed extract reduces these undesirable proteins, while at the same time increasing other proteins that are lost with age.14

The researchers concluded that polyphenols have diverse effects on brain aging.14 This research is also noteworthy in that it shows, for the first time, that “normal” aging can be reversed in a healthy adult rat. Most brain dementia studies examine diseased or aged brains instead of healthy ones.

Grape Seed for Bones and Metabolism

Grape seed extract is a very broad-spectrum supplement. It is a powerful antioxidant against diverse types of radicals; it stops ulcers as effectively as some drugs; it can keep sun-induced papillomas from turning into carcinomas; and it helps maintain bone in the jaw.56-59 This feature may help to preserve teeth. Studies have shown that healthy teeth and gums may reduce the risk of premature death.60 Bones, too, are important for health, as fractures greatly increase the risk of mortality.61

Grape seed extract and resveratrol together may have additive effects. In 1998, Japanese re-searchers first showed that resveratrol directly stimulates the cells that make bones.62 They subsequently demonstrated that resveratrol supplements maintain bone strength in older rats.63 Sun-dried skin also benefits from grape seed extract, which reverses some of the damage.64

Another benefit of grape seed extract is that it streamlines metabolism. This is very important for many reasons, but perhaps one of the most compelling is that blood sugar affects longevity, and “longevity genes” are linked to insulin and other factors having to do with metabolism.65,66 Type II diabetes has been characterized as “severe insulin resistance,” a condition that causes a form of premature aging.67,68 Clinical studies show that grape seed extract stabilizes blood sugar, mobilizes fat, and causes people to eat slightly less.69-71

The Future of Grape Nutraceuticals

Last year, Chinese researchers reported finding three new compounds in grape seed.72 All that is known about them so far is that they protect DNA against free radicals. What else they may do remains to be seen. Are they new “super-antioxidants”? Will they stop certain types of cancer? Will they chase off toxins? Or keep blood vessels and bones from aging? Nobody knows yet, but the prognosis is good that they will not disappoint us. The science of grapes is, to use the word of researchers, remarkable.


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: Accessed April 25, 2005.

10. Available at: 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:

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.

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.