Grape Seed

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For Patients & Caregivers

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 have also been shown to reduce cholesterol in patients with high cholesterol.

Only a few initial studies have been conducted to see whether grape seed extract can help cancer patients. One study is currently evaluating a pulverized grape skin supplement in prostate cancer patients. Another study did not find a grape seed extract effective for breast cancer patients following radiotherapy.

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 increased antioxidant levels in the blood.
To treat atherosclerosis
Although lab studies suggest substances within grape seeds may help reduce thickening of the arteries, further study is needed to determine whether Grape Seed Extract can reduce atherosclerosis in humans.
To prevent cancer or treat cancer
Only a few initial studies have been conducted to see whether grape seed extract can help cancer patients. One study is currently evaluating the effects of a pulverized grape skin supplement in prostate cancer patients. Another study did not find a grape seed extract effective for breast cancer patients following radiotherapy.
As a topical wound treatment
Animal studies have shown a possible effect, but further study is required to determine its effect in humans.

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 may 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.

For Healthcare Professionals

Vitis vinifera, Vitis coignetiae, Vitis rotundifolia

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

Animal studies suggest grape seed proanthocyanidin extract (GSPE) may help minimize cardiotoxicity induced by doxorubicin ⁽¹⁵⁾ and cyclosporine ⁽²²⁾, or drug-induced nephro- and pulmonary toxicities ⁽³⁾ ⁽²³⁾. GSPE also inhibits atherosclerosis ⁽⁴⁾ ⁽⁵⁾.

Small studies in humans suggest possible efficacy in decreasing LDL ⁽⁶⁾ and increasing total serum antioxidant activity ⁽⁷⁾. One study suggested benefits and antioxidative effects with grape seed extract for patients undergoing coronary artery bypass surgery ⁽¹¹⁾. 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⁾. In prostate cancer patients, a preliminary study of a pulverized muscadine grape skin from the species Vitis rotundifolia was safe and tolerable ⁽¹²⁾. Additional study is underway to determine whether there is clinical benefit in this population. However, 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
Cancer prevention
High cholesterol
Wound healing

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⁾.

Cytochrome P450 3A4 substrates: Grape seed extract inhibits CYP3A4 and can affect the intracellular concentration of drugs metabolized by this enzyme ⁽¹⁸⁾.
Anticoagulant/antiplatelet drugs: Due to the antiplatelet activity of grape seed, it may increase the risk of adverse effects of these drugs ⁽¹⁾ ⁽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⁾.

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.
Bombardelli E,.Morazzoni P. Vitis vinifera L. Fitoterapia 1995;66:291-317.
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.
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.
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.
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.
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.
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.
Bentivegna SS,.Whitney KM. Subchronic 3-month oral toxicity study of grape seed and grape skin extracts. Food Chem. Toxicol. 2002;40:1731-43.
Yamakoshi J, Saito M, Kataoka S, Kikuchi M. Safety evaluation of proanthocyanidin-rich extract from grape seeds. Food Chem. Toxicol. 2002;40:599-607.
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.
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.
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.
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.
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.
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.
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]
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.
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
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.
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.
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.
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.
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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Last Updated

Friday, March 30, 2018

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