Grape Seed

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Grape Seed

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Grape Seed

Common Names

  • Grape Seed Oil
  • Grape Seed Extract
  • Muskat

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For Patients & Caregivers

How It Works

Although it has antioxidant properties, grape seed has not been shown to treat or prevent cancer.

Grape Seed Extract is derived from the oil that comes from ground red wine grapes. The extract contains a substance called proanthocyanidin which has antioxidant activities. Proanthocyanidins may help improve cholesterol levels, but studies are limited. There are also very few studies that have been conducted in cancer patients. One such study did not find any improvements in radiotherapy side effects among breast cancer patients.

Grape seed extract should not be confused with Grapefruit seed extract (also known by the acronym GSE), which has different biological effects.

Purported Uses
  • To lower high cholesterol
    Grape seed may improve lipid profiles, but studies are limited and larger trials are needed.
  • To treat atherosclerosis
    Although lab studies suggest antioxidant and cardioprotective effects, studies in humans are lacking.
  • To address cancer side effects
    Studies in cancer patients are limited and have yet to show benefit.
Do Not Take If
  • You are taking warfarin or other blood thinners: Lab studies suggest grape seed may increase bleeding risk. Clinical relevance has yet to be determined.
  • You are taking cytochrome P450 3A4 substrate drugs: Lab studies suggest grape seed may increase their side effect risks. Clinical relevance has yet to be determined.
  • You are taking UGT substrate drugs: Lab studies suggest grape seed may increase their side effect risks. Clinical relevance has yet to be determined.
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For Healthcare Professionals

Scientific Name
Vitis vinifera, Vitis coignetiae, Vitis rotundifolia
Clinical Summary

Grape seeds are obtained as a by-product of wine production and ground to produce grape seed oil. Grape seed extract is marketed as a supplement for its antioxidant properties.

Preclinical studies of grape seed proanthocyanidin extract (GSPE) suggest cardioprotective (4) (5) and anticancer effects (16) (17). Other studies suggest synergistic effects with doxorubicin (13) or that it can help minimize various drug-induced toxicities (3) (15) (22) (23). Topical application accelerated wound contraction and closure (8).

Preliminary studies in humans suggest grape seed extract can reduce LDL (6), increase total serum antioxidant activity (7), and benefit patients undergoing coronary artery bypass surgery (11). Meta-analyses suggest GSE may lower systolic blood pressure and heart rate, but are mixed on whether it improves lipid, glucose, and inflammatory markers (24) (25). Other data suggest it may provide adjunctive benefit in patients with diabetic retinopathy (26).

Supplementation with grape seed may be associated with decreased risk of hematologic malignancies (21). In prostate cancer patients, a pulverized muscadine grape skin from Vitis rotundifolia was safe and tolerable (12), but clinical benefit needs to be assessed. Oral GSPE did not improve radiotherapy adverse effects of tissue hardness, pain, or tenderness in breast cancer patients (14).

Grape seed extract should not be confused with Grapefruit seed extract (also known by the acronym GSE), which has different biological effects.

Food Sources

Red wine grapes; compounds in grape seed extract are also found naturally in many other foods including fruits, vegetables, chocolate, and tea.

Purported Uses
  • Atherosclerosis
  • Cancer
  • High cholesterol
Mechanism of Action

Proanthocyanidins and minor phenolic compounds found in GSPE are also found naturally in many foods including fruits, vegetables, chocolate, and tea. People generally consume 460-1000 mg/day of these combined substances (9). GPSE has protective effects on doxorubin-induced cardiotoxicity (3). Cardioprotective effects may be due to its ability to modulate anti-apoptotic genes and modify molecular targets such as DNA damage and repair, lipid peroxidation, and intracellular calcium homeostasis (5).

Adverse Reactions

Gastrointestinal upset (26)

Herb-Drug Interactions
  • Anticoagulant/antiplatelet drugs: In vitro, grape seed has antiplatelet activity, and may increase the risk of adverse effects of these drugs (1) (19). Clinical relevance has yet to be determined.
  • Cytochrome P450 3A4 substrates: In vitro, GSE inhibits CYP3A4 and may affect the intracellular concentration of drugs metabolized by this enzyme (18). Clinical relevance has yet to be determined.
  • UGT (Uridine 5’-diphospho-glucuronosyltransferase) substrates: Grape seed modulates UGT enzymes in vitro and may increase the side effects of drugs metabolized by them (20). Clinical relevance has yet to be determined.
Dosage (OneMSK Only)
References
  1. Jin JW, Inoue O, Suzuki-Inoue K, et al. Grape seed extracts inhibit platelet aggregation by inhibiting protein tyrosine phosphatase. Clin Appl Thromb Hemost. Apr 2014;20(3):278-284.
  2. Bombardelli E,.Morazzoni P. Vitis vinifera L. Fitoterapia 1995;66:291-317.
  3. Ray SD, Patel D, Wong V, Bagchi D. In vivo protection of dna damage associated apoptotic and necrotic cell deaths during acetaminophen-induced nephrotoxicity, amiodarone-induced lung toxicity and doxorubicin-induced cardiotoxicity by a novel IH636 grape seed proanthocyanidin extract. Res Commun. Mol. Pathol. Pharmacol. 2000;107:137-66.
  4. 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;31:263-5.
  5. Bagchi D, Sen CK, Ray SD, Das DK, Bagchi M, Preuss HG et al. Molecular mechanisms of cardioprotection by a novel grape seed proanthocyanidin extract. Mutat. Res 2003;523-524:87-97.
  6. Preuss HG, Wallerstedt D, Talpur N, Tutuncuoglu SO, Echard B, Myers A et al. Effects of niacin-bound chromium and grape seed proanthocyanidin extract on the lipid profile of hypercholesterolemic subjects: a pilot study. J Med 2000;31:227-46.
  7. 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;23:385-9.
  8. Khanna S, Venojarvi M, Roy S, Sharma N, Trikha P, Bagchi D et al. Dermal wound healing properties of redox-active grape seed proanthocyanidins. Free Radic. Biol Med 2002;33:1089-96.
  9. Bentivegna SS,.Whitney KM. Subchronic 3-month oral toxicity study of grape seed and grape skin extracts. Food Chem. Toxicol. 2002;40:1731-43.
  10. Yamakoshi J, Saito M, Kataoka S, Kikuchi M. Safety evaluation of proanthocyanidin-rich extract from grape seeds. Food Chem. Toxicol. 2002;40:599-607.
  11. Safaei N, Babaei H, Azarfarin R, et al. Comparative effect of grape seed extract (Vitis vinifera) and ascorbic acid in oxidative stress induced by on-pump coronary artery bypass surgery. Ann Card Anaesth. Jan-Mar 2017;20(1):45-51.
  12. Paller CJ, Rudek MA, Zhou XC, et al. A phase I study of muscadine grape skin extract in men with biochemically recurrent prostate cancer: Safety, tolerability, and dose determination. Prostate. Oct 2015;75(14):1518-1525.
  13. Sharma G, Tyagi AK, Singh RP, Chan DC, Agarwal R. Synergistic anti-cancer effects of grape seed extract and conventional cytotoxic agent doxorubicin against human breast carcinoma cells. Breast Cancer Res Treat. 2004;85:1-12.
  14. 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.
  15. Li W, Xu B, Xu J, Wu XL. Procyanidins produce significant attenuation of doxorubicin-induced cardiotoxicity via suppression of oxidative stress. Basic Clin Pharmacol Toxicol. 2009 Mar;104(3):192-7.
  16. Song X, Siriwardhana N, Rathore K, Lin D, Wang HC. Grape seed proanthocyanidin suppression of breast cell carcinogenesis induced by chronic exposure to combined 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and benzo[a]pyrene. Mol Carcinog. 2010 May;49(5):450-63.
  17. Kaur M, Tyagi A, Singh RP, et al. Grape seed extract upregulates p21 (Cip1) through redox-mediated activation of ERK1/2 and posttranscriptional regulation leading to cell cycle arrest in colon carcinoma HT29 cells. Mol Carcinog. 2011 Jul;50(7):553-62.
  18. Etheridge AS, Black SR, Patel PR, So J, Mathews JM. An in vitro evaluation of cytochrome P450 inhibition and P-glycoprotein interaction with goldenseal, Ginkgo biloba, grape seed, milk thistle, and ginseng extracts and their constituents. Planta Med. 2007 Jul;73(8):731-41.
  19. Bijak M, Bobrowski M, Borowiecka M, et al. Anticoagulant effect of polyphenols-rich extracts from black chokeberry and grape seeds. Fitoterapia. 2011 Sep;82(6):811-7
  20. Mohamed ME, Frye RF. Effects of herbal supplements on drug glucuronidation. Review of clinical, animal, and in vitro studies. Planta Med. 2011 Mar;77(4):311-21.
  21. Walter RB, Brasky TM, Milano F, White E. Vitamin, mineral, and specialty supplements and risk of hematologic malignancies in the prospective VITamins And Lifestyle (VITAL) study.Cancer Epidemiol Biomarkers Prev. 2011;20(10):2298-308.
  22. Ozkan G, Ulusoy S, Alkanat M, et al. Antiapoptotic and antioxidant effects of GSPE in preventing cyclosporine A-induced cardiotoxicity. Ren Fail. 2012;34(4):460-6.
  23. Ulusoy S, Ozkan G, Ersoz S, et al. The effect of grape seed proanthocyanidin extract in preventing amikacin-induced nephropathy. Ren Fail. 2012;34(2):227-34.
  24. 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 Aug;111(8):1173-81.
  25. Asbaghi O, Nazarian B, Reiner Ž, et al. The effects of grape seed extract on glycemic control, serum lipoproteins, inflammation, and body weight: A systematic review and meta-analysis of randomized controlled trials. Phytother Res. Feb 2020;34(2):239-253.
  26. Moon SW, Shin YU, Cho H, et al. Effect of grape seed proanthocyanidin extract on hard exudates in patients with non-proliferative diabetic retinopathy. Medicine (Baltimore). May 2019;98(21):e15515.
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