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Grape Seed

Medically reviewed on Jun 14, 2018

Scientific Name(s): Vitis vinifera L., Vitis coignetiae Pulliat. Family: Vitaceae

Common Name(s): Grape seed , muskat , oligomeric proanthocyanidin complexes (OPC) , proanthocyanidin , procyanidolic oligomers (PCO) 1 , 2 , 3 , 4


Grape seed is known for its antioxidant properties. Limited studies suggest possible cardiovascular, chemopreventive, and cytoprotective effects.


Extracts of grape seeds containing mostly proanthocyanidin have been studied for antioxidant and cardiovascular properties, as well as for venous insufficiency and ophthalmologic disorders at doses of 50 to 300 mg/day. A maximum of 900 mg/day has been used.


Contraindicated in patients with known hypersensitivity to grape seed.


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


Caution is advised when administering supplements containing grape seed polyphenols concomitantly with vitamin C to hypertensive patients because increases in blood pressure may occur.

Adverse Reactions

None well documented. It is contraindicated in patients with known hypersensitivity to grape seed. Gastralgia, headache, and an allergic reaction have been reported in the literature. Additional clinical studies are recommended.


No toxicity in humans has been reported.


The plant is extensively cultivated in the northern hemisphere and probably originated in the Mediterranean and west Asian areas. 5 It has been successfully introduced to South America and the west coast of North America. 5 The woody vine climbs by tendrils that intermittently fork, and it sheds its bark. The thin, smooth, and shiny leaves may have 3, 5, or 7 lobes. 6 The elongated clusters of round or oval berries (ie, grapes) range in color from light green to purple black.


Grape seeds contain proanthocyanidin. 7 Proanthocyanidin extracts have been marketed in France for decades as treatment for venous and capillary disorders (eg, retinopathies, venous insufficiency, vascular fragility). 2

Red grape seeds are generally obtained as a by-product of wine production. When ground, these seeds become the source of grape seed oil. Red wine contains proanthocyanidin, and when used in association with a nonatherogenic diet, may reduce the incidence of cardiovascular disease. 2 , 4 , 7 , 8


The highest concentration of proanthocyanidins is found in the skin or membrane of the grape seed. 4 , 8 Total proanthocyanidin content consumed in 100 g of dry grape seed is approximately 3,500 mg. 9 Proanthocyanidins are one type of naturally occurring plant compounds called bioflavonoids. 4 The most active proanthocyanidins are those bound to other proanthocyanidins: mixtures of proanthocyanidin dimers, trimers, tetramers, and larger molecules such as PCO. 10 , 11 , 12

Grape seed oil contains nutritionally useful essential fatty acids and tocopherols (vitamin E). 12 The methanol extract of the oriental species ( V. coignetiae ) contains epsilon-viniferin; oligostilbenes; ampelopsins A, C, F; and the mixture of vitisin A and cis -vitisin A. 13 Dietary grape seed tannins and procyanidins (polyphenol oligomers) are reported. 14 , 15 Polyphenolic 5'-nucleotidase inhibitors designated as NPF-88BU-lA and NPF-88BU-lB, respectively, have been isolated from the seeds and skin of the wine grape. 16

Uses and Pharmacology

The majority of trials in humans have studied the use of grape seed extract as an antioxidant and for various cardiovascular disorders. Studies also suggest its use as a chemopreventive and cytoprotective agent. 1 , 7 , 17

Antioxidant effects
Animal data

A study in rats suggests that oral administration of 50 to 100 mg/kg grape seed proanthocyanidins for 72 hours may protect pancreatic tissue in experimental diabetes mellitus. 18

Clinical data

The antioxidant activity of 300 mg of grape procyanidin extracts in 2 capsules was investigated in a single-blind, randomized, placebo-controlled crossover study of 20 young volunteers. 19 Subjects were given 2 capsules or placebo for 5 days. Blood samples were taken at baseline and at the end of the study and then assayed for antioxidant activity as well as vitamin C and E levels. The study was repeated with a second treatment after a washout period of 2 weeks. The authors concluded that the extract did not affect serum vitamin C and E levels on day 5, but elevation of serum total antioxidant activity was statistically significant ( P < 0.01). 19

A case study of 3 patients with chronic pancreatitis whose symptoms were unresponsive to standard treatments reported a decrease in frequency and intensity of abdominal pain and vomiting when administered 200 to 300 mg/day of grape seed proanthocyanidin extract. 20 The authors stated that patients with pancreatitis have low blood concentrations of antioxidant factors and that antioxidants such as proanthocyanidin may be beneficial; however, further studies are required. 20

Cardiovascular effects
Animal data

A study in rats investigated the cardioprotective effects of grape seed proanthocyanidin at dosages of 50, 100, and 150 mg/kg administered orally via gastric gavage 6 days a week for 5 weeks prior to isoproterenol-induced myocardial infarction. 21 Dosages of 100 and 150 mg/kg lowered isoproterenol-induced serum concentrations of diagnostic marker enzymes (AST, ALT, LDH, and CK). These levels, an indication of the severity of necrotic damage to the myocardial membrane, were elevated in rats not receiving proanthocyanidin. Morphology of cardiac muscles was relatively well preserved in all proanthocyanidin groups with no evidence of focal necrosis, compared with the isoproterenol-induced heart. 21

Grape seed proanthocyanidin administered orally in two 200 mg/kg doses and intravenously (20 mg/kg) to mice exhibited antithrombotic effects on laser-induced thrombus formation in the carotid artery. 22

Another study involved a 1-year investigation in rats to determine if age-related insulin resistance could be overcome through the use of natural products, including grape seed extract. 23 Although a combination of agents was used in the study, the authors concluded that the activity of the antioxidant supplements (chromium polynicotinate, grape seed extract, zinc monomethionine) markedly lowered systolic blood pressure in normotensive rats, lowered HbA 1c , and reduced lipid peroxidation. 23

Clinical data

The effect of grape seed extract on capillary resistance disorders was studied in hypertensive and diabetic patients. 24 Overall, results were obtained in an open trial of 28 patients and during a double-blind versus placebo-controlled trial of 25 patients. Patients received 150 mg/day of the grape seed extract Endotelon . The drug was well tolerated in both groups and capillary resistance improved significantly ( P < 0.0005 and P < 0.005). 24

A randomized, double-blind, placebo-controlled trial in 40 hypercholesterolemic patients demonstrated that a combination of grape seed extract 100 mg twice daily and chromium polynicotinate 200 mcg twice daily over 2 months decreased total cholesterol and low-density lipoprotein compared with placebo. 25

A double-blind, placebo-controlled study in 24 patients with metabolic syndrome receiving 150 and 300 mg/day of grape seed extract for 4 weeks showed a decrease in systolic and diastolic pressure. 26 The authors suggest that grape seed extract may be used as adjunctive treatment in patients with mild hypertension, but further studies are required. 26

Animal data

The effects of dietary grape seed tannins on nutritional balance and on some enzymatic activities along the crypt-villus axis of the rat small intestine have been studied. 14 This study did not reveal tannin toxicity, except for reduced dry matter and nitrogen digestibility. However, the tannins directly interfered with mucosal proteins, stimulating cell renewal. 14

Wine grape seeds can be used as health oils because of their high content of essential fatty acids and tocopherols. 12

Clinical data

A randomized, double-blind, placebo-controlled, crossover trial of 51 healthy subjects administered grape seed extract 300 mg tablets 3 times a day 30 to 60 minutes before each meal for 3 days demonstrated no difference in 24-hour energy intake compared with placebo. 27 However, a subgroup analysis of subjects with energy requirements greater or equal to the median of 7.5 megajoules/day demonstrated that grape seed extract subjects had a lower 24-hour energy intake without affecting satiety, mood, and tolerance compared with placebo subjects. The authors suggest that grape seed extract may be used in healthy to overweight individuals with an unrestrained diet and higher energy requirements while sustaining satiety. 27 However, further research of longer duration and more accurate food intake measures are required.

Other uses

Other studies have shown that polyphenolic substances from the seeds and skin of the wine grapes (“Koshu”) can strongly inhibit 5'-nucleotidase activities from snake venom and rat liver membrane; have therapeutic activity in Ehrlich ascites carcinoma; have inhibitory action against the growth of Streptococcus mutans , a carcinogenic bacteria; and inhibit glucan formation from sucrose. 16 The latter 2 actions may indicate that these principles can aid in the prevention of dental caries.

Grape seed oil has been shown to be a safe and efficient hand-cleansing agent. 28

One study concluded that grape seed proanthocyanidin extract may offer a cytoprotective role in acetaminophen-induced hepatic DNA damage and apoptotic and necrotic cell death of liver cells. 29


Extracts of grape seed have been studied at doses of 50 to 900 mg/day for its antioxidant, cardiovascular, and nutritional effects as well as venous insufficiency and ophthalmologic complaints in Europe. 19 , 20 , 24 , 25 , 26 , 27 , 30 , 31


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


An increase in blood pressure in hypertensive patients taking 500 mg of grape seed polyphenols twice daily in combination with vitamin C 250 mg twice daily versus placebo or either supplement alone was demonstrated in a randomized double-blind, placebo-controlled trial. 32 Although the mechanism of this interaction remains to be elucidated, caution is advised when administering this combination to hypertensive patients.

Adverse Reactions

Grape seed is contraindicated in patients with known hypersensitivity. One trial of 35 patients with chronic venous insufficiency receiving grape seed extract 300 mg every 8 hours for 28 days reported 2 patients with gastralgia, 1 with a headache, and 1 experiencing an allergic reaction. 33


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 demonstrated chronic doses of 0.02%, 0.2%, and 2% (w/w) for 90 days did not produce signs of toxicity. 34


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21. Karthikeyan K , Bai BR , Devaraj SN . Cardioprotective effect of grape seed proanthocyanidins on isoproterenol-induced myocardial injury in rats . Int J Cardiol . 2007;115:326-333. Epub 2006 Jul 7.
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23. Preuss HG , Montamarry S , Echard B , Scheckenbach R , Bagchi D . Long-term effects of chromium, grape seed extract, and zinc on various metabolic parameters of rats . Mol Cell Biochem . 2001;223:95-102.
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