We are well acquainted with grape juice, wine, and the studies supporting the health benefits of these products. History records that the ancient Egyptians consumed grape products for medicinal purposes more than 6,000 years ago.1 Grape seed is usually considered the part of the grape that is discarded as useless. Increasing data indicate these tiny, ignored seeds may contain a tremendous number of antioxidants. According to the National Center for Complementary and Alternative Medicine, grape seed extract is used for cardiovascular disease, diabetes, neurologic conditions, vision problems, and wound healing.2


Grape seed extract’s mechanism of action results from the high concentration of phenolic compounds, or proanthocyanics, which are known to provide high levels of antioxidant activity.3 Grape seed also contains a significant number of essential fatty acids.4 Linoleic and oleic unsaturated fatty acids together compose nearly 90% of the oil in grape seed.4

Grape seed extract has shown vasodilitory and antiplatelet adhesion qualities.3 It also appears to decrease the chemicals that induce oxidative damage and increase the beneficial nitric oxide release from both endothelial cells and platelets.3 These lower systemic BP and maintain normal elasticity and tone by preventing intimal damage to blood vessels.3

Clinical trials

In a trial of 260 patients with chronic venous insufficiency, the treatment group received grape extract for up to 12 weeks.5 At the end of the study, the placebo-controlled group had an expected increase in lower leg edema and subjective symptoms whereas the treatment group showed a statistically significant reduction in these parameters from baseline.5 These effects were attributed to the vascular tone and anti-inflammatory effects of the treatment compound.

In another clinical trial, adult male smokers age 50 years and older were given grape seed extract for four weeks. Blood samples were taken at the end of the trial and compared with baseline for thiobarbituric acid reactive substances (TBARS).6 TBARS is the preferred screening and monitoring compound indicative of lipid peroxidation, a major indicator of oxidative stress that is typically elevated in smokers. The TBARS level at the end of treatment with grape seed extract was substantially lower than at baseline, indicating the potential for this product to be useful in mitigating the conversion of circulating fats into proinflammatory lipids and other compounds.6

A third study examined the in vitro effects of grape seed extract on human prostate cancer cells. A laboratory-maintained cell line of prostate cells with known carcinoma was subjected to grape seed extract washes and the results compared with baseline.7 It was shown that 16% more cancer cells died when treated with grape seed extract compared with 2.4% cell death in the untreated control.7 Cell death was the result of the dissipation of the mitochondrial membrane due to the effect of the extract.7

In a similar study, investigators examined in vitro human breast cancer cells and their response to grape seed extract. The focus of the study was the action of aromatase, the enzyme that converts androgen to estrogen.8 This enzyme is found in higher levels in breast cancer tissue than in normal breast tissue, and many oncology drugs target the blockage of this enzyme conversion. Grape seed extract not only blocked the enzyme conversion pathway, but reduced the formation of the enzyme itself.8 The authors concluded with a pronouncement that grape seed extract might be useful in the prevention and treatment of estrogen-receptor positive breast cancer.8

How supplied, dose, and cost

Grape seed extract is typically available in 50- and 100-mg tablets or capsules. The accepted adult dose range is 25-150 mg 1-3 times daily.1 Most grape seed products contain 80%-95% phenolic proanthocyanics.1 The cost is moderate, averaging $30/month for maximum dose therapy.

Safety, drug interactions

As with any grape product, allergic reactions have been noted with grape seed. More significant, however, is the potential for serious drug interactions. Grape seed extract is a potent inducer of one of the enzymes in the C-P450 hepatic chain. As such, it can cause a decrease in the drug levels of such common medications as warfarin, acetaminophen, calcium channel blockers, and tricyclic antidepressants.3 Side effects include headache, dry or itchy scalp, dizziness, and nausea.2 There is insufficient evidence to rate safety in young children or women who are pregnant or lactating.3


We are well aware of the constant damage done to our cell structures by oxidative effects from free radicals and other proinflammatory entities. While grape seed is certainly not the only natural compound to exert these protective effects, it is worth considering when consulting with patients about their health. Careful attention should be paid, however, to the significant drug interaction profile of grape seed, and patients should be screened for the use of these medications.


1. University of Maryland Medical Center. Grape seed.

2. National Center for Complementary and Alternative Medicine. Grape seed extract.

3. Memorial Sloan-Kettering Cancer Center. Grape seed.

4. Yilmaz Y, Toledo RT. Oxygen radical absorbance capabilities of grape/wine industry byproducts and effect of solvent type on extraction of grape seed polyphenols. J Food Compost Anal. 2006;19:41-48.

5. Kiesewetter H, Koscielny J, Kalus U, et al. Efficacy of orally administered extract of red vine leaf AS 195 (folia vitis viniferae) in chronic venous insufficiency (stages I-II): A randomized, double-blind, placebo-controlled trial. Arzneimittelforschung. 2000;50:109-117.

6. Vigna GB, Constantini F, Aldini G, et al. Effect of a standardized grape seed extract on low-density lipoprotein susceptibility to oxidation in heavy smokers. Metabolism. 2003;52:1250-1257.

7. Agarwal C, Singh RP, Agarwal R. Grape seed extract induces apoptotic death of human prostate carcinoma DU145 cells via caspases activation accompanied by dissipation of mitochondrial membrane potential and cytochrome c release. Carcinogenesis. 2002;23:1869-1876.

8. Kijima I, Phung S, Hur G, et al. Grape seed extract is an aromatase inhibitor and a suppressor of aromatase expression. Cancer Res. 2006;66:5960-5967.

All electronic documents accessed January 20, 2010.