Scientific Name(s): Vitis vinifera L.
Common Name(s): Grape seed, Grape seed extract, Muskat, Oligomeric proanthocyanidin complexes (OPC), Proanthocyanidin, Procyanidolic oligomers (PCO)
Grape seed is known for its antioxidant properties. Limited studies suggest possible roles in cardiovascular disease, neurodegenerative disorders, and cancer.
Composition of commercial preparations is highly variable. Extracts of grape seed have been studied in clinical trials at doses of 150 to 2,000 mg/day.
Contraindicated in patients with known hypersensitivity to grape products.
Information regarding safety and efficacy in pregnancy and lactation is lacking.
See Drug Interactions section.
Generally well tolerated.
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 black.1, 2
Grape leaves have been found in fossils dating back to prehistoric times. Grapes were domesticated in western Asia prior to 5,000 BC and have been mentioned in biblical writings and depicted in tomb paintings dating to 2,400 BC. Jesuit priests brought Spanish grapes to Mexico in the 17th century, establishing 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 by-product of wine making, is used in cooking and salad dressings.2, 3, 4
Grape seeds contain vitamin E; polyphenols, including gallic acid, catechins, proanthocyanidins, and tannins; polyunsaturated fatty acids, including linoleic, oleic, and alpha-linolenic acids; protein; and carbohydrates.
Despite marketing claims, cold-pressed grape seed oil contains little proanthocyanidin content because of 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.5, 6, 7, 8, 9
Uses and Pharmacology
Studies conducted primarily in mice and human cancer cell lines (including prostate, lung, gastric, and squamous cell carcinoma) have shown grape seed extract to induce cell cycle arrest and promote apoptosis.11 Antiangiogenic activity has also been demonstrated.12 Decreased incidence of induced tumors and a reduction of transformation to carcinoma have been demonstrated in models of skin cancer.9, 11, 13, 14, 46 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. 11, 12
Clinical trials have been initiated among postmenopausal women to evaluate the protective effect of grape seed extract on breast cancer, as well as to measure estrogen levels, though the results have not been published.12, 15 Among women with radiation fibrosis, no effect on breast induration was found with grape seed extract.16
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 supports improved endothelial function and endothelial-dependent relaxation in aortic tissue.17, 18, 19, 20
Clinical trials have been conducted in healthy volunteers, hypertensive and hyperlipidemic patients, and in patients with metabolic syndrome and type 2 diabetes. Participant numbers are small, and grape seed products and dosages used vary considerably among the trials.21, 22, 23, 47, 48 A meta-analysis was conducted on 9 trials that found significant reductions in heart rate (−1.42 beats per minute [bpm], [95% confidence interval (CI), −2.5 to −0.34 bpm; 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.21 No significant effect was found on diastolic blood pressure, lipids, or C-reactive protein, and insufficient patient numbers did not allow for analysis of harm.21 A small, randomized, placebo-controlled trial (n = 70) in adults with systolic blood pressures of 120 to 159 mm Hg found no significant reduction in blood pressure with grape seed extract.47
A small randomized, placebo-controlled, crossover trial (n = 52) conducted in mildly hyperlipidemic adults and published after the meta-analysis found small reductions in total cholesterol (−10.68 ± 26.76 mg/dL, P = .015) and low-density lipoprotein cholesterol (−9.66 ± 23.92 mg/dL, P = .014).48 Similar results were seen with a commercially available combination product of 1.5% (5.025 mg) red yeast rice that also contained 30 mg coenzyme Q10, 20 mg procyanidins from grape seed, and 100 mg lecithin. Data from 52 participants with a 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 in 20% of the intervention group and a 15% reduction in total cholesterol (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 side effects were noted between treatment and placebo, although muscle aches tended to be more prevalent in the intervention group.49 Larger trials are required to validate positive results demonstrated on serum lipid indices in some studies.24 Trial data are lacking for effect of grape seed on specific cardiovascular events; however, the results from several trials, including participants with hypertension, diastolic heart failure, coronary artery bypass graft-induced oxidative stress, metabolic syndrome, and coronary heart disease, are pending.15, 21
In studies in mouse models of Alzheimer disease, grape seed extract reduced neuropathy and cognitive deterioration.25 Experiments in mouse models of Huntington disease and other neurodegenerative disorders have been conducted.25
Studies in mice have shown enhanced wound-healing properties, and grape seed extract has been evaluated for effect on aging skin.33, 34 Compared with placebo, wound healing time was statistically significantly reduced with 2% grape seed cream for postsurgical wounds that were between 3 mm and 1 cm in size on the neck, trunk, and limbs in a double-blind, randomized controlled trial (n = 40) in Iranian patients 14 to 50 years of age. Average time to heal was 8 days versus 14 days for grape seed versus placebo, respectively. By day 10, 100% of wounds treated with grape seed were healed compared with 28.2% for placebo (P = 0.0001).50
Women with chloasma showed a decrease in hyperpigmentation in an open-label study.35
Grape seed extract may be used in healthy and overweight individuals with an unrestrained diet and higher energy requirements while sustaining satiety.36
Composition of commercial preparations is highly variable.7
Grape seed extract has been studied in clinical trials at doses of 150 to 2,000 mg/day. A dose of 300 mg/day has been studied over 24 weeks.21
Pregnancy / Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking.
Agents with antiplatelet properties: Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of agents with antiplatelet properties. Bleeding may occur. Consider therapy modification.37, 38, 39, 40
Herbs (anticoagulant/antiplatelet properties): Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of other herbs (anticoagulant/antiplatelet properties). Bleeding may occur. Consider therapy modification.37, 38, 39, 40
Nonsteroidal anti-inflammatory agents: Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of nonsteroidal anti-inflammatory agents. Bleeding may occur. Consider therapy modification.37, 38, 39, 40
Other interaction data
Some studies have reported insignificant pharmacokinetic drug interactions with natural products. Limited information as well as potentially high interpatient variability in clinical response warrants cautious interpretation and/or application of these data in practice.
Although concentrations of dextromethorphan and its active metabolite dextrorphan increased in 57% of healthy subjects after 3 days of grape seed extract (200 to 300 mg/day grape seed phytosome) supplementation, the mean difference was found to be statistically and clinically insignificant. Slow CYP2D6 metabolizers were excluded from the study.45
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.25, 42
Trans resveratrol caused renal damage in rats administered 3 g/kg/day over 4 weeks.43 Dogs have developed renal failure following consumption of both seeded and seedless grapes and raisins; however, not all consumption results in toxicity, which may be caused by a mycotoxin.44
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