About Herbs, Botanicals & Other Products

Scientific Name
Vitis vinifera, Vitis coignetiae
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Common Name

Grape Seed Oil, Grape Seed Extract, muskat

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Brand Name

ActiVin® eganaturalTM Leucoselect®

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Clinical Summary

Obtained as a by-product of wine production, grape seeds are ground to produce grape seed oil. Traditionally, grape seed oil and grape seed extract (GSE) have been used as a laxative, antacid, cholagogic agent, in treating burns, ulcers, and as a hand cleanser (1) (2). Studies of grape seed proanthocyanidin extract (GSPE) in mice have shown effectiveness in minimizing doxorubicin-induced cardiotoxicity (15) as well as other drug-induced nephrotoxicity, pulmonary toxicity (3). GSPE also inhibits atherosclerosis (4) (5).
Small human trials have shown possible efficacy in decreasing LDL (6) and increasing total serum antioxidant activity (7). Additionally, topical application of GSPE has been shown to accelerate wound contraction and closure (8).

In vitro studies have shown GSPE to have anticancer effects (16) (17) and synergistic effects with doxorubicin (13). Supplementation with grape seed may be associated with decreased risk of hematologic malignancies (21).
But orally administered GSPE was not effective for breast induration following radiotherapy in patients with breast cancer (14).
Few side effects have been reported with GSPE consumption, however, because it inhibits cytochrome P450, it may affect the metabolism of certain drugs.

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Food Sources

Red Wine Grapes

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Purported Uses
  • Atherosclerosis
  • Burns
  • Cancer prevention
  • Constipation
  • GI disorders
  • High cholesterol
  • Wound healing
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Constituents
  • Oligomeric proanthocyanidins (OPC): dimeric, trimeric and tetrameric OPCs, cathechin derivatives, other flavonoids (3)
  • Lipids: palmitic, stearic, oleic, linoleic, sitosterol and tocopherols. Phosphatidylserine, phosphatidylinositol, lecithin, cephalin, cerebrosides and phosphatic acid are bound to seed lipoproteins.
  • Proteins: leucine, arginine, cystine, phenylalanine, valine (2).
  • Tocopherol
  • Tannins (1)
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Mechanism of Action

Proanthocyanidins and minor phenolic compounds found in GSPE are also found naturally in many foods including fruits, vegetables, chocolate and tea. On average, people consume 460-1000 mg/day of these combined substances (9). Procyanidins, subunits of proanthocyanidins, from V. vinifera seeds have been shown to have antioxidant activity and to alter capillary permeability in animal models (2). GPSE has protective effects on doxorubin-induced cardiotoxicity (3). Cardioprotective effects theoretically come from its ability to modulate anti-apoptotic genes and modify molecular targets such as DNA damage and repair, lipid peroxidation and intracellular calcium homeostasis (5). Procyanidins also inhibit xanthine oxidase activity and non-competitively inhibit the proteolytic enzymes collagenase and elastase and the glycosidases hyaluronidase and beta-glucuronidase. Polyphenolic substances from grape seeds have been shown to inhibit the growth of Streptococcus mutans and glucan formation from sucrose, which may aid in the prevention of dental caries. Seed tannins may stimulate cell renewal by interfering with mucosal proteins (1).

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Pharmacokinetics

GSPE is an inhibitor of cytochrome P450 (3). Gastrointestinal absorption of GSPE is rapid. 70% of the extract is eliminated within the first 24 hours, most through the urine and feces although some through the bile (2).

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Herb-Drug Interactions
  • Cytochrome P450 3A4 substrates: Grape seed extract inhibits CYP3A4 and can affect the intracellular concentration of drugs metabolized by this enzyme (18).
  • Warfarin (Coumadin): Due to its anticoagulant effects, grape seed can enhance the activity of warfarin (11) (12) (19).
  • UGT (Uridine 5’-diphospho-glucuronosyltransferase) substrates: Grape seed modulates UGT enzymes in vitro and can increase the side effects of drugs metabolized by them (20).
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Literature Summary and Critique

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.
A randomized controlled trial testing total cholesterol and LDL change in forty subjects with total cholesterol levels of 210-300 mg/dL. Subjects were randomized into one of four groups to receive either placebo, Chromium Polynicotinate (Cr) 200 micrograms twice daily, Grape Seed Extract (GSE) 100 mg twice daily or both Cr and GSE intervention. After two months, a significant decrease in total cholesterol and LDL was observed only for the Cr and GSE combination group. HDL and triglyceride levels did not change significantly for any group. The two groups receiving GSE also showed a decrease in circulating autoantibodies to oxidized LDL. Further study is needed to determine whether GSE has a role in treating hypercholesterolemia.

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References
  1. DerMarderosian A. The Review of Natural Products. St. Louis: Facts and Comparisons, 1999.
  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. Kim JM,.White RH. Effect of vitamin E on the anticoagulant response to warfarin. Am J Cardiol. 1996;77:545-6.
  12. Corrigan JJ, Jr.,.Marcus FI. Coagulopathy associated with vitamin E ingestion. JAMA 1974;230:1300-1.
  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. [Epub ahead of print]
  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 May 6. [Epub ahead of print]
  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 Jul 29. [Epub ahead of print]
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How It Works

Bottom Line: 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 have also been shown to reduce cholesterol in patients with high cholesterol. Other substances within the grape seed may also help protect teeth from decay.

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Purported Uses
  • To lower high cholesterol
    One study showed a combination of Grape Seed Extract and chromium to be effective at lowering cholesterol levels.
  • As an antioxidant
    One small study showed Grape Seed Extract to increase antioxidant levels in the blood.
  • To treat atherosclerosis
    Although studies have shown that substances found within grape seeds may have an effect in reducing the thickening of arteries, further study is needed to determine whether Grape Seed Extract will reduce atherosclerosis in humans.
  • As a topical wound treatment
    Animal studies have shown a possible effect, but further study is required to determine its effect in humans.
  • As a laxative
    No scientific evidence supports this use.
  • As an antacid
    This claim is not supported by research.
  • To treat ulcers
    There is no evidence to back this claim.
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Research Evidence

High Cholesterol:
Forty patients with high cholesterol took part in a study of chromium and Grape Seed Extract (GSE) for high cholesterol. For two months, patients received one of four treatments: placebo, chromium, Grape Seed Extract or chromium and Grape Seed Extract together. Only those taking the chromium and Grape Seed Extract had significantly reduced total cholesterol and LDL (“bad”) cholesterol levels. While this study shows that Grape Seed Extract may play a role in reducing cholesterol levels when combined with chromium, larger studies need to be done to determine what effect the extract has by itself.

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Patient Warnings
  • This product is regulated by the FDA as a dietary supplement. Unlike approved drugs, supplements are not required to be manufactured under specific standardized conditions. The product may not contain the labeled amount. In addition, it may not have been tested for safety or effectiveness.
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Do Not Take If
  • You are taking drugs that are substrates of Cytochrome P450 3A4 (Grape seed may increase the risk of side effects of these drugs).
  • You are taking Warfarin or other blood thinners (Grape seed can increase the risk of bleeding).
  • You are taking drugs that are substrates of UGT (Uridine 5’-diphospho-glucuronosyltransferase) enzymes (grape seed may increase the risk of side effects of these drugs).
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Dosage (Inside MSKCC Only)
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Last updated: August 8, 2011
E-mail your questions and comments to aboutherbs@mskcc.org.