Grape Seed

Grape Seed

Grape Seed

Common Names

  • Grape Seed Oil
  • Grape Seed Extract
  • muskat

For Patients & Caregivers

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.

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

  • 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.

Cardiovascular Health:
Nine randomized controlled trials involving 390 patients were included in this meta analysis. The studies had to report efficacy data on at least one of the following end points: systolic or diastolic blood pressure, heart rate, total cholesterol, low-density or high-density lipoprotein cholesterol, triglycerides, or CRP. Results showed that grape seed extract significantly lowered systolic blood pressure. No significant effect on diastolic blood pressure, lipid levels, or CRP was found.

  • 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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For Healthcare Professionals

ActiVin® eganatural<sup>TM</sup> Leucoselect®
Vitis vinifera, Vitis coignetiae

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, to treat burns, ulcers, and as a hand cleanser (1)(2). Studies of grape seed proanthocyanidin extract (GSPE) in mice have shown effectiveness in minimizing cardiotoxicity induced by doxorubicin (15) , cyclosporine (22); and drug-induced nephro- and pulmonary toxicities (3)(23). GSPE also inhibits atherosclerosis (4)(5).
Small human trials have shown possible efficacy in decreasing LDL (6) and increasing total serum antioxidant activity (7). Conclusions from a meta analysis indicate that grape seed extract significantly lowers systolic blood pressure and heart rate, but does not affect lipid or CRP levels (24).
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).

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

Red Wine Grapes

  • Atherosclerosis
  • Burns
  • Cancer prevention
  • Constipation
  • GI disorders
  • High cholesterol
  • Wound healing
  • Oligomeric proanthocyanidins (OPC): dimeric, trimeric and tetrameric OPCs, cathechin derivatives, other flavonoids
  • 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
  • Tocopherol
  • Tannins
    (3)

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).

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

  • 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).

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.
Nine randomized controlled trials involving 390 patients were included in this meta analysis. The studies had to report efficacy data on at least one of the following end points: systolic or diastolic blood pressure, heart rate, total cholesterol, low-density or high-density lipoprotein cholesterol, triglycerides, or CRP. Results showed that grape seed extract significantly lowered systolic blood pressure (P=0.02]), and heart rate (P=0.01]). No significant effect on diastolic blood pressure, lipid levels, or CRP was found. Larger randomized, double-blinded trials are warranted to evaluate different dosages of grape seed extract and for longer follow-up periods.

  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. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Bentivegna SS,.Whitney KM. Subchronic 3-month oral toxicity study of grape seed and grape skin extracts. Food Chem. Toxicol. 2002;40:1731-43.

  9. Yamakoshi J, Saito M, Kataoka S, Kikuchi M. Safety evaluation of proanthocyanidin-rich extract from grape seeds. Food Chem. Toxicol. 2002;40:599-607.

  10. Kim JM,.White RH. Effect of vitamin E on the anticoagulant response to warfarin. Am J Cardiol. 1996;77:545-6.

  11. Corrigan JJ, Jr.,.Marcus FI. Coagulopathy associated with vitamin E ingestion. JAMA 1974;230:1300-1.

  12. 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.

  13. 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.

  14. 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]

  15. 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.

  16. 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.

  17. 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.

  18. 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.

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