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Grape Seed

Scientific Name(s): Vitis vinifera L.
Common Name(s): Grape seed, Grape seed extract, Muskat, Oligomeric proanthocyanidin complexes (OPC), Proanthocyanidin, Procyanidolic oligomers (PCO)
Drug class: Herbal products

Medically reviewed by Last updated on Aug 16, 2021.

Clinical Overview


Grape seed is known for its antioxidant properties. Limited studies suggest possible roles in cardiovascular disease, neurodegenerative disorders, and cancer.


Composition of commercial preparations is highly variable. Extracts of grape seed have been studied in clinical trials at doses of 150 to 2,000 mg/day.


Contraindicated in patients with known hypersensitivity to grape products.


Information regarding safety and efficacy in pregnancy and lactation is lacking.


See Drug Interactions section.

Adverse Reactions

Generally well tolerated.


None reported.

Scientific Family

  • Vitaceae


V. vinifera is a deciduous climber with several stems, tendrils, clusters of pale-green flowers, and palm-shaped leaves. Grapes are native to southern Europe and western Asia but are cultivated in temperate regions throughout the world. French hybrid varieties of grapes were developed mainly for wine making. The berries grow in bunches of 6 to 300 grapes on woody, climbing vines and range in color from light green to purple black.1, 2


Grape leaves have been found in fossils dating back to prehistoric times. Grapes were domesticated in western Asia prior to 5,000 BC and have been mentioned in biblical writings and depicted in tomb paintings dating to 2,400 BC. Jesuit priests brought Spanish grapes to Mexico in the 17th century, establishing vineyards in what is now Socorro, New Mexico, the area of the earliest grape plantings in the United States. Ancient Egyptians, Romans, and Greeks noted the health benefits of wine drinking, and the cardioprotective effect of regular wine consumption has been observed among Mediterranean populations. Grape seed extract and proanthocyanidins have been marketed in France for decades as treatment for venous and capillary disorders, and the extract is used extensively in Japan as a food additive and antioxidant. Cold-pressed grape-seed oil, obtained as a by-product of wine making, is used in cooking and salad dressings.2, 3, 4


Grape seeds contain vitamin E; polyphenols, including gallic acid, catechins, proanthocyanidins, and tannins; polyunsaturated fatty acids, including linoleic, oleic, and alpha-linolenic acids; protein; and carbohydrates.

Despite marketing claims, cold-pressed grape seed oil contains little proanthocyanidin content because of insolubility in lipids, and no resveratrol, which is found primarily in grape skin. Total proanthocyanidin content consumed in 100 g of dried grape seed is approximately 3,500 mg, although composition of commercial preparations is highly variable.5, 6, 7, 8, 9

Uses and Pharmacology

Much of the efficacy of grape seed extract is attributed to its high antioxidant activity.9, 10


Animal data

Studies conducted primarily in mice and human cancer cell lines (including prostate, lung, gastric, and squamous cell carcinoma) have shown grape seed extract to induce cell cycle arrest and promote apoptosis.11 Antiangiogenic activity has also been demonstrated.12 Decreased incidence of induced tumors and a reduction of transformation to carcinoma have been demonstrated in models of skin cancer.9, 11, 13, 14, 46 In breast cancer models in mice and in human breast cancer cell lines, grape seed extract has been shown to reduce the expression of aromatase. 11, 12

Clinical data

Clinical trials have been initiated among postmenopausal women to evaluate the protective effect of grape seed extract on breast cancer, as well as to measure estrogen levels, though the results have not been published.12, 15 Among women with radiation fibrosis, no effect on breast induration was found with grape seed extract.16

Cardiovascular effects

Animal data

Studies conducted in rodents, dogs, and rabbits have demonstrated positive effects of grape seed extract on reducing myocardial infarct size, thrombus formation, and reperfusion injury. Animal data also supports improved endothelial function and endothelial-dependent relaxation in aortic tissue.17, 18, 19, 20

Clinical data

Clinical trials have been conducted in healthy volunteers, hypertensive and hyperlipidemic patients, and in patients with metabolic syndrome and type 2 diabetes. Participant numbers are small, and grape seed products and dosages used vary considerably among the trials.21, 22, 23, 47, 48 A meta-analysis was conducted on 9 trials that found significant reductions in heart rate (−1.42 beats per minute [bpm], [95% confidence interval (CI), −2.5 to −0.34 bpm; P = 0.01]) and in systolic blood pressure (−1.54 mm Hg [95% CI, −2.85 to −0.22; P = 0.02]), which may be related to the reduced heart rate.21 No significant effect was found on diastolic blood pressure, lipids, or C-reactive protein, and insufficient patient numbers did not allow for analysis of harm.21 A small, randomized, placebo-controlled trial (n = 70) in adults with systolic blood pressures of 120 to 159 mm Hg found no significant reduction in blood pressure with grape seed extract.47

A small randomized, placebo-controlled, crossover trial (n = 52) conducted in mildly hyperlipidemic adults and published after the meta-analysis found small reductions in total cholesterol (−10.68 ± 26.76 mg/dL, P = .015) and low-density lipoprotein cholesterol (−9.66 ± 23.92 mg/dL, P = .014).48 Similar results were seen with a commercially available combination product of 1.5% (5.025 mg) red yeast rice that also contained 30 mg coenzyme Q10, 20 mg procyanidins from grape seed, and 100 mg lecithin. Data from 52 participants with a total fasting cholesterol higher than 200 mg/dL and triglycerides less than 400 mg/dL revealed that 2 capsules taken twice daily for 8 weeks produced a 22% reduction in LDL cholesterol in 20% of the intervention group and a 15% reduction in total cholesterol (P < 0.001); magnitude of effect on LDL was high and ranged from −8% to 40.5%. No significant differences in creatine-kinase elevation or side effects were noted between treatment and placebo, although muscle aches tended to be more prevalent in the intervention group.49 Larger trials are required to validate positive results demonstrated on serum lipid indices in some studies.24 Trial data are lacking for effect of grape seed on specific cardiovascular events; however, the results from several trials, including participants with hypertension, diastolic heart failure, coronary artery bypass graft-induced oxidative stress, metabolic syndrome, and coronary heart disease, are pending.15, 21


Animal data

In studies in mouse models of Alzheimer disease, grape seed extract reduced neuropathy and cognitive deterioration.25 Experiments in mouse models of Huntington disease and other neurodegenerative disorders have been conducted.25

Clinical data

Limited clinical studies have been conducted to evaluate the role of grape seed in mild cognitive impairment.15, 25, 26

Other uses


Protective effects of grape seeds have been demonstrated in models of renal, hepatic, and pancreatic toxicity, the mechanism of which may be related to antioxidant activity. 27, 28, 29


Grape seed’s role in dentistry has been suggested because of effects on Streptococcus mutans, inhibition of glucan formation from sucrose, and induction of cross-linking in dentin.30, 31, 32


Studies in mice have shown enhanced wound-healing properties, and grape seed extract has been evaluated for effect on aging skin.33, 34 Compared with placebo, wound healing time was statistically significantly reduced with 2% grape seed cream for postsurgical wounds that were between 3 mm and 1 cm in size on the neck, trunk, and limbs in a double-blind, randomized controlled trial (n = 40) in Iranian patients 14 to 50 years of age. Average time to heal was 8 days versus 14 days for grape seed versus placebo, respectively. By day 10, 100% of wounds treated with grape seed were healed compared with 28.2% for placebo (P = 0.0001).50

Women with chloasma showed a decrease in hyperpigmentation in an open-label study.35


Grape seed extract may be used in healthy and overweight individuals with an unrestrained diet and higher energy requirements while sustaining satiety.36


Composition of commercial preparations is highly variable.7

Grape seed extract has been studied in clinical trials at doses of 150 to 2,000 mg/day. A dose of 300 mg/day has been studied over 24 weeks.21

Pregnancy / Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.


Agents with antiplatelet properties: Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of agents with antiplatelet properties. Bleeding may occur. Consider therapy modification.37, 38, 39, 40

Anticoagulants: Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of anticoagulants. Bleeding may occur. Consider therapy modification.37, 38, 39, 40

Herbs (anticoagulant/antiplatelet properties): Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of other herbs (anticoagulant/antiplatelet properties). Bleeding may occur. Consider therapy modification.37, 38, 39, 40

Nonsteroidal anti-inflammatory agents: Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of nonsteroidal anti-inflammatory agents. Bleeding may occur. Consider therapy modification.37, 38, 39, 40

Salicylates: Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of salicylates. Bleeding may occur. Consider therapy modification.39, 40

Thrombolytic agents: Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of thrombolytic agents. Bleeding may occur. Consider therapy modification.37, 38, 39, 40

Other interaction data

Some studies have reported insignificant pharmacokinetic drug interactions with natural products. Limited information as well as potentially high interpatient variability in clinical response warrants cautious interpretation and/or application of these data in practice.

Although concentrations of dextromethorphan and its active metabolite dextrorphan increased in 57% of healthy subjects after 3 days of grape seed extract (200 to 300 mg/day grape seed phytosome) supplementation, the mean difference was found to be statistically and clinically insignificant. Slow CYP2D6 metabolizers were excluded from the study.45

Adverse Reactions

Grape seed is contraindicated in patients with known hypersensitivity. Clinical trials have generally reported grape seed extract to be well tolerated.25, 41


No human toxicity has been reported for grape seed. A safety evaluation of proanthocyanidin from grape seeds administered orally to mice demonstrated no evidence of toxicity and mutagenicity at acute doses of 2 and 4 g/kg. In addition, the same study found that doses of 0.02%, 0.2%, and 2% (w/w) for 90 days were not toxic.25, 42

Trans resveratrol caused renal damage in rats administered 3 g/kg/day over 4 weeks.43 Dogs have developed renal failure following consumption of both seeded and seedless grapes and raisins; however, not all consumption results in toxicity, which may be caused by a mycotoxin.44


1. Vitis vinifera L. USDA, NRCS. 2012. PLANTS Database. ( April 27, 2012. National Plant Data Team, Greensboro, NC 27401-4901 USA.
2. Chevallier A. The Encyclopedia of Medicinal Plants. New York, NY: DK Publishing; 1996:281.
3. Bertelli AA, Das DK. Grapes, wines, resveratrol, and heart health. J Cardiovasc Pharmacol. 2009;54(6):468-476.19770673
4. Murray M, Pizzorno J. Encyclopedia of Natural Medicine. 2nd ed. Rocklin CA: Prima Publishing; 1998.
5. Gu L, Kelm MA, Hammerstone JF, et al. Concentrations of proanthocyanidins in common foods and estimations of normal consumption. J Nutr. 2004;134(3):613-617.14988456
6. Joshi SS, Kuszynski CA, Bagchi D. The cellular and molecular basis of health benefits of grape seed proanthocyanidin extract. Curr Pharm Biotechnol. 2001;2(2):187-200.11480422
7. Nakamura Y, Tsuji S, Tonogai Y. Analysis of proanthocyanidins in grape seed extracts, health foods and grape seed oils. J Health Sci. 2003;49(1):45-54.NoPubMedID
8. Duke JA. Handbook of Medicinal Herbs. 2nd ed. Boca Raton FL: CRC Press; 2003.
9. Kidd PM. Bioavailability and activity of phytosome complexes from botanical polyphenols: the silymarin, curcumin, green tea, and grape seed extracts. Altern Med Rev. 2009;14(3):226-246.19803548
10. 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(5):385-389.9875688
11. Kaur M, Agarwal C, Agarwal R. Anticancer and cancer chemopreventive potential of grape seed extract and other grape-based products. J Nutr. 2009;139(9):1806S-1812S.19640973
12. Khan SI, Zhao J, Khan IA, Walker LA, Dasmahapatra AK. Potential utility of natural products as regulators of breast cancer-associated aromatase promoters. Reprod Biol Endocrinol. 2011;9:91.21693041
13. Katiyar SK. Grape seed proanthocyanidines and skin cancer prevention: inhibition of oxidative stress and protection of immune system. Mol Nutr Food Res. 2008 Jun;52 Suppl 1:S71-S76.18384090
14. Nichols JA, Katiyar SK. Skin photoprotection by natural polyphenols: anti-inflammatory, antioxidant and DNA repair mechanisms. Arch Dermatol Res. 2010;302(2):71-83.19898857
15. US National Institutes of Health. Grape seed. Accessed May 20, 2014.
16. 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. Radiother Oncol. 2006;79(1):45-51.16546280
17. Karthikeyan K, Bai BR, Devaraj SN. Cardioprotective effect of grape seed proanthocyanidins on isoproterenol-induced myocardial injury in rats. Int J Cardiol. 2007;115(3):326-333.16828181
18. 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):115-121.15567462
19. Leifert WR, Abeywardena MY. Cardioprotective actions of grape polyphenols. Nutr Res. 2008;28(11):729-737. 19083481
20. Lanati N, Emanuele E, Brondino N, Geroldi D. Soluble RAGE-modulating drugs: state-of-the-art and future perspectives for targeting vascular inflammation. Curr Vasc Pharmacol. 2010;8(1):86-92.19485931
21. Feringa HH, Laskey DA, Dickson JE, Coleman CI. The effect of grape seed extract on cardiovascular risk markers: a meta-analysis of randomized controlled trials. J Am Diet Assoc. 2011;111(8):1173-1181.21808563
22. Ghosh D, Scheepens A. Vascular action of polyphenols. Mol Nutr Food Res. 2009;53(3):322-331.19051188
23. Cherniack EP. Polyphenols: planting the seeds of treatment for the metabolic syndrome. Nutrition. 2011;27(6):617-623.21367579
24. Weseler AR, Ruijters EJ, Drittij-Reijnders MJ, Reesink KD, Haenen GR, Bast A. Pleiotropic benefit of monomeric and oligomeric flavanols on vascular health—a randomized controlled clinical pilot study. PLoS One. 2011;6(12):e28460.22174811
25. Ho L, Pasinetti GM. Polyphenolic compounds for treating neurodegenerative disorders involving protein misfolding. Expert Rev Proteomics. 2010;7(4):579-589.20653511
26. Carlson S, Peng N, Prasain JK, Wyss JM. Effects of botanical dietary supplements on cardiovascular, cognitive, and metabolic function in males and females. Gend Med. 2008;5 Suppl A:S76-90.18395685
27. Ali BH, Al Za'abi M, Blunden G, Nemmar A. Experimental gentamicin nephrotoxicity and agents that modify it: a mini-review of recent research. Basic Clin Pharmacol Toxicol. 2011;109(4):225-232.21599835
28. Ray SD, Kumar MA, Bagchi D. A novel proanthocyanidin IH636 grape seed extract increases in vivo Bcl-XL expression and prevents acetaminophen-induced programmed and unprogrammed cell death in mouse liver. Arch Biochem Biophys. 1999;369(1):42-58.10462439
29. Banerjee B, Bagchi D. Beneficial effects of a novel IH636 grape seed proanthocyanidin extract in the treatment of chronic pancreatitis. Digestion. 2001;63(3):203-206.11351148
30. Toukairin T, Uchino K, Iwamoto M, et al. New polyphenolic 5'-nucleotidase inhibitors isolated from the wine grape "Koshu" and their biological effects. Chem Pharm Bull (Tokyo). 1991;39(6):1480-1483.1934168
31. Macedo GV, Yamauchi M, Bedran-Russo AK. Effects of chemical cross-linkers on caries-affected dentin bonding. J Dent Res. 2009;88(12):1096-1100. 19892915
32. Wu CD. Grape products and oral health. J Nutr. 2009;139(9):1818S-1823S.19640974
33. Baumann LS. Less-known botanical cosmeceuticals. Dermatol Ther. 2007;20(5):330-342.18045358
34. Skovgaard GR, Jensen AS, Sigler ML. Effect of a novel dietary supplement on skin aging in post-menopausal women. Eur J Clin Nutr. 2006;60(10):1201-1206.16670692
35. Yamakoshi J, Sano A, Tokutake S, et al. Oral intake of proanthocyanidin-rich extract from grape seeds improves chloasma. Phytother Res. 2004;18(11):895-899.15597304
36. 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;58(4):667-673.15042136
37. Mousa SA. Antithrombotic effects of naturally derived products on coagulation and platelet function. Methods Mol Biol. 2010;663:229-240.20617421
38. Stanger MJ, Thompson LA, Young AJ, et al. Anticoagulant activity of select dietary supplements. Nutr Rev. 2012;70(2):107-117.22300597
39. Spolarich AE, Andrews L. An examination of the bleeding complications associated with herbal supplements, antiplatelet and anticoagulant medications. J Dent Hyg. 2007;81(3):67.17908423
40. Ulbricht C, Chao W, Costa D, et al. Clinical evidence of herb-drug interactions: a systematic review by the Natural Standard Research Collaboration. Curr Drug Metab. 2008;9(10):1063-1120.19075623
41. Martinez MJ, Bonfill X, Moreno RM, Vargas E, Capellá D. Phlebotonics for venous insufficiency. Cochrane Database Syst Rev. 2005;(3):CD003229.16034893
42. Yamakoshi J, Saito M, Kataoka S, Kikuchi M. Safety evaluation of proanthocyanidin-rich extract from grape seeds. Food Chem Toxicol. 2002;40(5):599-607.11955665
43. Chen XW, Serag ES, Sneed KB, Zhou SF. Herbal bioactivation, molecular targets and the toxicity relevance. Chem Biol Interact. 2011;192(3):161-176.21459083
44. McKnight K. Grape and raisin toxicity in dogs. Vet Tech. 2005:135-136.
45. Goey AK, Meijerman I, Beijnen JH, Schellens JH. The effect of grape seed extract on the pharmacokinetics of dextromethorphan in healthy volunteers. Eur J Clin Pharmacol. 2013;69(11):1883-1890.23881421
46. Perde-Schrepler M, Chereches G, Brie I, et al. Grape seed extract as photochemopreventive agent against UVB-induced skin cancer. J Photochem Photobiol B. 2013;118:16-21.23178081
47. Ras RT, Zock PL, Zebregs YE, Johnston NR, Webb DJ, Draijer R. Effect of polyphenol-rich grape seed extract on ambulatory blood pressure in subjects with pre- and stage I hypertension. Br J Nutr. 2013 Dec;110(12):2234-41.23702253
48. Razavi SM, Gholamin S, Eskandari A, et al. Red grape seed extract improves lipid profiles and decreases oxidized low-density lipoprotein in patients with mild hyperlipidemia. J Med Food. 2013;16(3):255-258.23437789
49. Verhoeven V, Hartmann ML, Remmen R, Wens J, Apers S, Van Royen P. Red yeast rice lowers cholesterol in physicians-a double blind, placebo controlled randomized trial. BMC Complement Altern Med. 2013;13:178.23866314
50. Hemmati AA, Foroozan M, Houshmand G, Moosavi ZB, Bahadoram M, Maram NS. The topical effect of grape seed extract 2% cream on surgery wound healing. Glob J Health Sci. 2015;7(3):52-58.25948437


This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

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