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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), Wine grape

Medically reviewed by Last updated on Jun 21, 2022.

Clinical Overview


Grape seed is known for its antioxidant properties. Studies suggest a possible role in cardiovascular disease. However, large quality clinical trials are lacking to recommend use for any indication.


Composition of commercial grape seed preparations is highly variable. In clinical trials, grape seed extract has been studied for effects on various cardiovascular risk markers at oral doses of 150 to 2,000 mg/day; formulations and durations of therapy (range, 2 to 24 weeks) varied.


Grape seed is contraindicated in individuals with known hypersensitivity to grape products.


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


See Drug Interactions section.

Adverse Reactions

Grape seed is generally well tolerated.


No data.

Scientific Family

  • Vitaceae (grape)


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 to black.Chevallier 1996, USDA 2020


Grape leaves have been found in fossils dating back to prehistoric times. Grapes were domesticated in western Asia prior to 5,000 BC, are depicted in tomb paintings dating to 2,400 BC, and are mentioned in biblical writings. Jesuit priests brought Spanish grapes to Mexico in the 17th century, then established 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 byproduct of wine making, is used in cooking and salad dressings.Bertelli 2009, Chevallier 1996, Murray 1998


Grape seeds contain vitamin E; polyphenols, including gallic acid, catechins, proanthocyanidins, resveratrol, and tannins; polyunsaturated fatty acids, including linoleic, oleic, and alpha-linolenic acids; protein; and carbohydrates. Other grape seed oil constituents include tocopherol, quercetin, procyanidins, carotenoids, and phytosterols.Garavaglia 2016 Despite marketing claims, cold-pressed grape seed oil contains little proanthocyanidin content because of its 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.Duke 2002, Gu 2004, Joshi 2001, Kidd 2009, Nakamura 2003

Uses and Pharmacology

Grape seed oil has demonstrated various effects indicating potential health benefits, such as anti-inflammatory, cardioprotective, antimicrobial, and anticancer properties, mainly identified by in vitro studies.Garavaglia 2016 Much of the efficacy of grape seed extract is attributed to its high antioxidant activity.Kidd 2009, Nuttall 1998 Grape seeds and its biologically active constituent resveratrol exert protective effects against various natural or chemical toxins that could alter physiological homeostasis through a variety of mechanisms. Some mechanisms of action include an increase in superoxide dismutase, heme oxygenase 1, and glutathione peroxidase activities; reduced glutathione content and malondialdehyde (MDA) levels; and activation of the Nrf2/ARE pathway.Tabeshpour 2018


A review concluded that proanthocyanidins found in grape seed oil and extract resulted in proliferation of hair follicle cells isolated from mice (by approximately 230% relative to 100% in controls) and possessed remarkable hair cycle-converting activity from the telogen phase to the anagen phase in C3H mice in vivo test systems.Dhariwala 2019

Antioxidant activity

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.Ali 2011, Banerjee 2001, Ray 1999


Animal and in vitro data

In vitro studies conducted primarily in mouse models and human cancer cell lines (including prostate, lung, gastric, and squamous cell carcinoma) have shown grape seed extract induces cell cycle arrest and promotes apoptosis.Kaur 2009 Antiangiogenic activity has also been demonstrated.Khan 2011 Decreased incidence of induced tumors and a reduction in transformation to carcinoma have been demonstrated in skin cancer models.Katiyar 2008, Kaur 2009, Kidd 2009, Nichols 2010, Perde-Schrepler 2013 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.Kaur 2009, Khan 2011 Cell line models have also shown that grape seed procyanidin extracts mediate antineoplastic effects against lung cancer via modulations of prostacyclin and 15-HETE eicosanoid pathways.Mao 2016

Clinical data

Among women with radiation fibrosis, grape seed extract administration had no effect on breast induration.Brooker 2006

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 support improved endothelial function and endothelial-dependent relaxation in aortic tissue.Karthikeyan 2007, Lanati 2010, Leifert 2008, Sano 2005

Clinical data

Clinical trials have been conducted in healthy volunteers, in patients with hypertension and hyperlipidemia, and in patients with metabolic syndrome and type 2 diabetes. Participant numbers are small, and grape seed products and dosages used vary considerably among trials.Cherniack 2011, Feringa 2011, Ghosh 2009, Ras 2013, Razavi 2013 In a meta-analysis of 9 trials (N=390) evaluating the beneficial effects of grape seed extract on cardiovascular risk markers, grape seed extract total daily doses ranged from 150 to 2,000 mg and treatment durations ranged from 2 to 24 weeks. Grape seed extract was associated with significant reductions in heart rate (−1.42 beats per minute [bpm]; 95% CI, −2.5 to −0.34; 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. No significant effects were found on diastolic blood pressure, lipids, or C-reactive protein, and insufficient patient numbers did not allow for analysis of harm.Feringa 2011 In a small, randomized, placebo-controlled trial in adults with systolic blood pressure of 120 to 159 mm Hg (N=70), no significant reduction in blood pressure was observed with grape seed extract (300 mg/day for 8 weeks) compared with placebo. The authors concluded that consumption of polyphenol-rich grape seed extract does not lower ambulatory blood pressure in untreated subjects with pre- and stage I hypertension.Ras 2013 In addition, consumption of grape polyphenols has no major impact on flow-mediated dilation or vascular function in a study of healthy men.van Mierlo 2010 Conversely, in a small study in individuals with prehypertension (N=36), grape seed extract formulated in a low-energy functional beverage was safe and improved blood pressure, supporting the use of grape seed extract as a functional ingredient (ie, in a low-energy beverage) for blood pressure control.Park 2016

Both grape seed extract and vitamin C have antioxidative effects and have each shown the ability to reduce the deleterious effects of cardiopulmonary bypass during coronary artery bypass graft surgery.Safaei 2017 A small randomized, placebo-controlled, crossover trial in adults with mild hyperlipidemia (N=52) and published after the previously described meta-analysis found small reductions in total cholesterol (−10.68±26.76 mg/dL; P=0.015) and low-density lipoprotein cholesterol (LDL-C) (−9.66±23.92 mg/dL; P=0.014) with red grape seed extract 200 mg/day (duration, 8 weeks) compared with placebo.Razavi 2013 Similar results were observed with a commercially available 1.5% (5.025 mg) red yeast rice combination product that also contained 30 mg of coenzyme Q10, 20 mg of procyanidins from grape seed, and 100 mg of lecithin. Data from 52 participants with 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 and a 15% reduction in total cholesterol in the intervention group compared with control (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 adverse effects were noted between treatment and placebo, although muscle aches tended to be more prevalent in the intervention group.Verhoeven 2013

In a randomized, double-blind, placebo-controlled clinical trial, patients with moderate hyperlipidemia (N=70) received treatment with red grape seed extract 200 mg/day or placebo for 8 weeks. Significant elevations in serum levels of apolipoprotein Al (apo-AI) (P=0.001), high-density lipoprotein cholesterol (HDL-C) (P=0.001), and paraoxonase (PON) activity (P=0.001), and marked decreases in concentrations of total cholesterol (P=0.015), triglycerides (P=0.011), and LDL-C (P=0.014) were observed. PON activity was significantly correlated with apo-AI (r=0.27; P<0.01) and HDL-C (r=0.45; P<0.001). Significant differences between the red grape seed extract and control groups (before and after treatment) for total cholesterol (P=0.001), triglycerides (P=0.001), PON (P=0.03), apo-AI (P=0.001), and LDL-C (P=0.002) were observed. The authors concluded that red grape seed extract might increase PON activity, mostly through increasing HDL-C and apo-AI levels, and may have potential beneficial effects in preventing oxidative stress and atherosclerosis.Argani 2016

Larger trials are required to validate the positive results demonstrated on serum lipid indices in some studies.Weseler 2011 Large-scale trial data are also lacking regarding effects of grape seed on specific cardiovascular events.Feringa 2011, NIH 2014


Animal data

In studies using mouse models of Alzheimer disease, grape seed extract reduced neuropathy and cognitive deterioration. Experiments using mouse models for Huntington disease and other neurodegenerative disorders have also been conducted.Ho 2010

Clinical data

Limited clinical studies have been conducted to evaluate the role of grape seed in mild cognitive impairment.Carlson 2008, Ho 2010, NIH 2014

Dental effects

A role for grape seed in dentistry has been suggested because of effects on Streptococcus mutans, inhibition of glucan formation from sucrose, and induction of cross-linking in dentin.Macedo 2009, Toukairin 1991, Wu 2009 A reduction in the oral streptococci count has also been demonstrated following use of V. vinifera 12.5% mouthwash extract.Singla 2018 In a randomized clinical study in individuals with chronic periodontitis, a randomized clinical study showed that subgingival application of a formulated mucoadhesive grape seed extract 2% gel produced improvement in the plaque index and gingival index after 6 months of application.Rayyan 2018

Dermatologic effects

Animal data

Studies in mice have shown enhanced wound-healing properties.Baumann 2007 In a preclinical mouse model, dietary proanthocyanidins prevented ultraviolet radiation-induced nonmelanoma skin cancer through enhanced repair of damaged DNA-dependent activation of immune sensitivity.Katiyar 2017

Clinical data

In a study of healthy postmenopausal women, a dietary supplement containing grape seed was evaluated for effects on aging skin.Skovgaard 2006 In a double-blind, randomized controlled trial in Iranian patients 14 to 50 years of age with postsurgical wounds between 3 mm and 1 cm in size on the neck, trunk, and limbs (N=40), wound healing time was statistically significantly reduced with grape seed 2% cream compared with placebo. Average time to healing was 8 days and 14 days for grape seed and placebo, respectively. By day 10, 100% of wounds treated with grape seed were healed compared with 28.2% for placebo (P=0.0001).Hemmati 2014 Another study in women undergoing caesarean section suggests a grape seed extract 5% ointment may also have beneficial therapeutic effects in promoting caesarean section wound healing.Izadpanah 2019 Women with chloasma showed a decrease in hyperpigmentation in an open-label study.Yamakoshi 2004

Diabetic retinopathy

Clinical data

In a randomized, multicenter, double-blind trial, patients with nonproliferative diabetic retinopathy (N=124; 40 to 78 years of age) were administered placebo, calcium dobesilate (750 mg/day), or grape seed proanthocyanidin extract (GSPE) (150 mg/day) orally for up to 12 months. All patients had retinal thickening with hard exudates. Rate of improvement in those with hard exudates was higher in the GSPE group than in the calcium dobesilate group. In the GSPE group, total macular volume after 9 months of treatment was decreased compared with baseline. It was determined that oral GSPE therapy for 1 year improves hard exudates in patients with nonproliferative diabetic retinopathy.Moon 2019

Leg swelling

Single-intake trials and 14-day intake trials were held for a small-scale (N=16), double-blind, placebo-controlled, crossover clinical trial evaluating grape seed extract in healthy Japanese women with leg swelling. A prolonged sedentary position was maintained for 6 hours after grape seed extract or placebo administration. Leg volume distension, increased body extracellular fluid, and leg water were suppressed in the grape seed extract groups.Sano 2013


Clinical data

A randomized, double-blind, placebo-controlled study was conducted in women 40 to 60 years of age with at least one menopausal symptom (N=96). Participants were randomized to receive grape seed extract tablets containing either low-dose (100 mg/day) or high-dose (200 mg/day) proanthocyanidin or placebo for 8 weeks. A total of 91 women (95%) completed the study. It was concluded that GSPE is effective in improving the physical and psychological symptoms of menopause while increasing muscle mass and reducing blood pressure in middle-aged women.Terauchi 2014

Metabolic syndrome

Results of a review of in vitro, in vivo, and clinical studies determined V. vinifera is a potential candidate for treatment of metabolic syndrome because the grape polyphenols have significant effects on blood glucose levels, lipid profiles, and blood pressure, as well as beneficial activities in liver and heart.Akaberi 2016

Nutrition and exercise performance

Results of a randomized, placebo-controlled, double-blind, crossover study in healthy and overweight individuals with an unrestrained diet and higher energy requirements (N=51) demonstrate that grape seed extract may be effective in reducing 24-hour energy intake while sustaining satiety.Vogels 2004 In addition, grape seed extract supplementation may also act as an ergogenic aid able to prolong the onset of fatigue during physical activity.Kim 2018


Composition of commercial grape seed preparations is highly variable.Nakamura 2003 In clinical trials, grape seed extract has been studied for effects on various cardiovascular risk markers at oral doses of 150 to 2,000 mg/day; formulations and durations of therapy (range, 2 to 24 weeks) varied.Feringa 2011 In a safety and tolerability assessment in healthy Japanese adult volunteers, oral intake of grape seed extract up to 2,500 mg for 4 weeks was found to be generally safe and well tolerated.Sano 2017

Pregnancy / Lactation

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


Grape seed extracts have dual anticoagulant/antiplatelet activity due to the high polyphenolic content.(Bijak 2019)

Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of agents with antiplatelet properties. Bleeding may occur.(Mousa 2010, Spolarich 2007, Stanger 2012, Ulbricht 2008)

Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of anticoagulants. Bleeding may occur.(Choi 2017, Fan 2017, Heck 2000, Izzat 1998, Jiang 2005, Kruth 2004, Lambert 2001, Mousa 2010, Spolarich 2007, Stanger 2012, Tsai 2013, Ulbricht 2008, Vaes 2000, Wang 2015)

Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of other herbs (anticoagulant/antiplatelet properties). Bleeding may occur.(Mousa 2010, Spolarich 2007, Stanger 2012, Ulbricht 2008)

Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of nonsteroidal anti-inflammatory agents. Bleeding may occur.(Mousa 2010, Spolarich 2007, Stanger 2012, Ulbricht 2008)

Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of salicylates. Bleeding may occur.(Mousa 2010, Spolarich 2007, Stanger 2012, Ulbricht 2008)

Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of thrombolytic agents. Bleeding may occur.(Mousa 2010, Spolarich 2007, Stanger 2012, Ulbricht 2008)

CYP-450 enzyme-mediated herbal drug interactions are possible; caution should be exercised.(Wanwimolruk 2014)

Dextromethorphan: Grape seed may increase the serum concentration of dextromethorphan. No action needed.(Goey 2013)

Adverse Reactions

Grape seed is contraindicated in individuals with known hypersensitivity. Clinical trials have generally reported that grape seed extract is well tolerated.Ho 2010, Martinez 2005


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.Ho 2010, Yamakoshi 2002 Trans-resveratrol caused renal damage in rats administered 3 g/kg/day over 4 weeks.Chen 2011 Dogs have developed renal failure following consumption of both seeded and seedless grapes and raisins, possibly caused by a mycotoxin; however, not all consumption results in toxicity.McKnight 2005



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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