- Oligomeric proanthocyanidins (OPCs)
- ActiVin®, bioflavinols, catechin, condensed tannins, drue kerne, Endotelon®, enocianina, epicatechin, extrait de pepins de raisin, gallic acid, grape complex, grape seed oil, grape skin extract, grapeseed, grapeseed extract (GSE), grapeseed oil, IH636 grape seed proanthocyanidin, Indena’s Grape Seed Standardized Extract®, leucoanthocyanidins, Leucoselect®-phytosome, Masquelier’s Original OPCs®, muskat, nonhydrolyzable tannins, oligomeres procyanidoliques, pine bark extract, procyanidolic oligomers (PCOs), polyphenolic oligomers, pycnogenol, Pycnogenol®, tannins, Vitaceae (family), Vitis cognetiae, Vitis vinifera L.
- Note: Pycnogenol® is a patented nutrient supplement extracted from the bark of European coastal pine Pinus maritima. Pycnogenol® consists of flavonoids, catechins, procyanidins, and phenolic acids, which are the same things found in grape seed, but not the same supplement.
- Grape leaves, sap and fruit have been used medicinally since the time of the Greek empire. Preparations from different parts of the plant have been used historically to treat a variety of conditions, including skin and eye irritation, bleeding, varicose veins, diarrhea, cancer and smallpox.
- Interest in grape products for heart disease prevention increased with reporting of possible protective effects from wine consumption in French men who also consume a high fat diet (the so-called “French paradox”). However, well-designed controlled trials of the proposed active component of grape seed extract (GSE), the oligomeric proanthocyanidins (OPCs), are lacking. It is important to note that grape seed extract and Pycnogenol® are not the same even though they both contain oligomeric proanthocyanidins. Pycnogenol® is a patented nutrient supplement extracted from the bark of European coastal pine Pinus maritima.
- The antioxidant properties of OPCs have made products containing these extracts candidate therapies for a wide range of human disease. Randomized, controlled trials have documented the effectiveness of OPCs from grape seed in relieving symptoms of chronic venous insufficiency, injury related extremity edema, diabetic retinopathy, arteriosclerosis and high blood pressure. Grape seed extract has been used by natural practitioners in Europe to treat venous insufficiency, promote wound healing, alleviate inflammatory conditions, and as a “cardioprotective” therapy.
- OPCs appear to be well tolerated with few side effects noted in the available literature. However, long-term studies assessing safety are lacking.
These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.
Human studies report that extract from grape seed can reduce the symptoms of poor circulation in leg veins. Symptoms that showed significant improvements include itching, swelling, heaviness, nighttime cramps, tingling, burning, numbness and nerve pain.
Several small human studies show that grape seed ingredients may speed the reduction of swelling after many types of injury, including surgery. Further research is needed in this area.
Diabetic retinopathy is a disease of the small blood vessels in the retina of the eye. Early study using OPCs, and the brand name product Endotelon®, have shown beneficial effects in stopping the disease progression.
Small human studies suggest that ingredients from grape seed may make small blood vessels less fragile and less likely to leak.
Grape seed oil is a popular (non scented) carrier oil used in aromatherapy. Although grape seed has been compared to lavender oil and thyme oil to reduce agitation in patients with dementia, there is not enough scientific evidence to make a strong recommendation about its effectiveness.
Studies have found grape seed to be an antioxidant, which may help prevent or relieve symptoms of certain conditions, such as vision problems associated with diabetes and wound healing. The safety of long-term use of grape seed is unknown, and more studies are needed to provide definitive answers.
There is little information available on the use of grape seed extract in the treatment of human cancer (prostate, skin, breast, etc.). Further research is needed before a recommendation can be made.
Historical statistics suggest that wine may reduce the risk of heart disease. Animal studies suggest that grape seed may decrease cholesterol deposits in blood vessels and may reduce the amount of injury to heart muscle during a “heart attack.”
Early human and animal studies show that extracts of grape seed can block the ability of platelets to form a clot (resulting in “thinner” blood). This effect seems to be more prominent in smokers.
Chloasma (melasma) is a skin discoloration that may occur due to hormonal imbalances. Antioxidants are thought to improve chloasma, and grape seed extract is thought to have antioxidant activity. Additional research is needed to confirm these findings.
A small human study suggests that grape seed may reduce abdominal pain in chronic pancreatitis. Animal studies suggest that some grape seed ingredients may protect the liver from injury. Further research is needed on the effectiveness of grape seed extract to treat pancreatitis and other gastrointestinal disorders.
Little information is available for the use of grape seed extract in the treatment premenstrual symptoms. Early study shows positive results but further research is necessary before a recommendation can be made.
Some grape seed ingredients may protect the skin from the harmful affects of UV radiation by acting as antioxidants. One human study reports a small benefit from grape seed in reducing redness after exposure to UV light. Grape seed may also promote hair growth. More information is needed before a recommendation can be made.
Epicatechin is an antioxidant component of grape seed extract which has become increasingly popular in skin products. Combination products that include grape seed extract have shown promising effects. Additional study of grape seed’s effects as a single agent is needed to make a strong recommendation.
Several small studies suggest that grape seed may slow the progression of retinopathy (damage to the retina caused by diabetes or high blood pressure). Visual performance may be improved in healthy patient as well. Further research is needed in this area.
Grape seed has been used to treat immune system disorders due to its antioxidant effects. However, a well-designed human study of allergic rhinitis sufferers showed no improvement in allergy symptoms with administration of grape seed extract ingredients.
Grape seed extract has been studied for its radioprotective effects in breast cancer patients with tissue hardening after radiotherapy. Although early results show a lack of benefit, additional larger studies investigating other doses of grape seed are warranted to confirm this finding.
*Key to grades:
The below uses are based on tradition, scientific theories, or limited research. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. There may be other proposed uses that are not listed below.
Adults (18 years and older)
- Grape seed is commercially available as grape seed extract, which is typically standardized to its proanthocyanidin content. Oligomeric proanthocyanidins (OPCs) found in grape seed (as well as pine bark extract) are also available. Two popularly studied products are ActiVin® and Endotelon®. Grape seed extract is also sold as tinctures, capsules, and as an ingredient in topical creams.
- There is strong scientific evidence that Endotelon® (procyanidolic oligomers, which are found in grape seed) taken in a dose of 150-300 milligrams per day for 28-30 days is an effective dosing range for poor circulation in leg veins. Other doses have been studied, but show unclear effectiveness. For instance, 150-400 milligrams Endotelon® for up to two months for conditions such as post-operative swelling, diabetic retinopathy, vascular fragility, and other vision problems has been studied. For diabetic retinopathy, 100-200 milligrams of OPCs has been taken for up to one year. Grape seed extract, standardized to its proanthocyanidin content, in a dose of 100-400 milligrams has also been taken three times a day for up to six months for radioprotection. ActiVin® 200-300 milligrams per day has also been studied for chronic pancreatitis.
Children (younger than 18 years)
- There is no proven safe and effective dose of grape seed or OPCs in children.
The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.
- There are reports of people with allergy to grapes or other grape compounds, including anaphylaxis. Individuals allergic to grapes should not take grape seed and related products.
Side Effects and Warnings
- Natural medicine practitioners generally regard OPCs as safe. Reported side effects include scalp dryness or itch, hives, headache, high blood pressure, nausea, indigestion, or dizziness. There are mixed reports as to whether compounds found in grape seed can damage the liver, but grape seed extract as a whole is thought to protect the liver.
- Use cautiously in patients taking anticoagulants such as warfarin, aspirin, non-steroidal anti-inflammatory drugs (NSAIDS), or anti-platelet agents, as OPCs may alter platelet function and the ability to form clots. Based on animal studies, grape seed may increase the risk of bleeding. Caution is advised in patients with bleeding disorders or taking drugs that may increase the risk of bleeding. Dosing adjustments may be necessary. Avoid in people with disorders that increase their risk of bleeding or who have active bleeding disorders (stomach ulcers, bleeding into the brain, etc.). Stop all use of grape seed extract at least two weeks prior to surgery or dental procedures.
- Grape seed may interfere with the way the body processes certain drugs using the liver’s “cytochrome P450” enzyme system. Therefore, the levels of these drugs may be altered in the blood and may cause potentially serious effects. If using any medications, check the package insert and speak with a qualified healthcare provider and pharmacist about possible interactions.
- Caution is also advised in patients with blood pressure disorders or those taking ACE inhibitors.
Pregnancy and Breastfeeding
- The use of grape seed during pregnancy or breastfeeding is not recommended due to lack of safety information.
The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.
Interactions with Drugs
- In theory, grape seed extract or OPCs may increase the risk of bleeding when taken with drugs that increase the risk of bleeding. Some examples include aspirin, anticoagulants (“blood thinners”) such as warfarin (Coumadin®) or heparin, anti-platelet drugs such as clopidogrel (Plavix®), and non-steroidal anti-inflammatory drugs such as ibuprofen (Motrin®, Advil®) or naproxen (Naprosyn®, Aleve®). However, human cases are lacking. OPCs may theoretically alter the effectiveness of prescribed blood pressure medications that are angiotensin converting enzyme (ACE) inhibitors like Capoten® (captopril).
- OPCs may interact with medications such as methotrexate and allopurinol leading to severe side effects in people taking these medications. OPCs may interfere with the way the body processes certain drugs using the liver’s “cytochrome P450” enzyme system. As a result, the levels of these drugs may be increased or decreased in the blood, and change the intended effects.
- Grape seed may lower cholesterol and may have additive effects with other cholesterol-lowering medications such as HMGCoA reductase inhibitors (“statins”) like lovastatin (Mevacor®).
- OPCs may also interact with agents used to control nausea and vomiting (antiemetics), agents used for cancer, and folate analogs. A qualified healthcare professional, including a pharmacist, should be consulted to check for interactions.
Interactions with Herbs and Dietary Supplements
- In theory, grape seed or OPCs may increase the risk of bleeding when taken with herbs and supplements that are believed to increase the risk of bleeding. Multiple cases of bleeding have been reported with the use of Ginkgo biloba, fewer cases with garlic, and some with saw palmetto. Numerous other agents may theoretically increase the risk of bleeding, although this has not been proven in most cases.
- OPCs may interfere with the way the body processes certain herbs or supplements using the liver’s “cytochrome P450” enzyme system. As a result, the levels of other herbs or supplements in the blood may be too high or too low. It may also alter the effects that other herbs or supplements possibly have on the P450 system.
- One study reports that Leucoselect®-phytosome (an OPC preparation) has no effect on vitamin C levels, although unofficial reports suggest that some ingredients from grape seed may enhance the absorption and effectiveness of vitamins C and E.
- Grape seed may lower cholesterol and may have additive effects with other cholesterol-lowering herbs/supplements such as niacin and red yeast.
- OPCs may also interact with herbs or supplements used to control nausea and vomiting (antiemetics) or for cancer. OPCs may also have additive effects with antioxidants or alter folate metabolism. Taking grape seed and the probiotic, Lactobacillus acidophilus, may prevent colonization of the gastrointestinal tract. Caution is also advised when taking grape seed or OPCs with herbs that affect the heart or blood pressure, and interactions are possible. A qualified healthcare professional, including a pharmacist, should be consulted to check for interactions.
Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.
- This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration ().
- Amsellem M, Masson JM, Negui B, et al. [Endotelon in the treatment of venolymphatic problems in premenstrual syndrome. Multicenter study on 165 patients]. Tempo Medical 1987;282 :46-51.
- Banerjee B, Bagchi D. Beneficial effects of a novel ih636 grape seed proanthocyanidin extract in the treatment of chronic pancreatitis. Digestion 2001;63(3):203-206.
- Bernstein CK, Deng C, Shuklah R, et al. Double blind placebo controlled (DBPC) study of grapeseed extract in the treatment of seasonal allergic rhinitis (SAR). J Allergy Clin Immunol 2001;107(2):s311.
- 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 Apr;79(1):45-51.
- Lesbre FX, Tigaud JD. [The effect of Endotelon on the capillary fragility index of a specified controlled group: cirrhosis patients]. Gazette Medicale de France 1983;90(24):2333-2337.
- Nuttall SL, Kendall MJ, Bombardelli E, et al. An evaluation of the antioxidant activity of a standardized grape seed extract, Leucoselect. Journal of Clinical Pharmacology and Therapeutics 1998;23:385-389.
- Oshima Y, Namao K, Kamijou A, et al. Powerful hepatoprotective and hepatotoxic plant oligostilbenes, isolated from the Oriental medicinal plant Vitis coignetiae (Vitaceae). Experientia 1-15-1995;51(1):63-66.
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- Preuss HG, Wallerstedt D, Talpur N, 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(5-6):227-246.
- Rimm EB, Williams P, Fosher K, et al. Moderate alcohol intake and lower risk of coronary heart disease: meta-analysis of effects on lipids and haemostatic factors. BMJ 1999;319(7224):1523-1528.
- Skovgaard GR, Jensen AS, Sigler ML. Effect of a novel dietary supplement on skin aging in post-menopausal women. Eur J Clin Nutr. 2006 Oct;60(10):1201-6.
- Snow LA, Hovanec L, Brandt J. A controlled trial of aromatherapy for agitation in nursing home patients with dementia. J Altern Complement Med 2004;10(3):431-437.
- Spadea L, Balestrazzi E. Treatment of vascular retinopathies with Pycnogenol. Phytother Res 2001;15(3):219-223.
- Vaswani SK, Chang BW, Carey RN, et al. Adult onset grape hypersensitivity causing life threatening anaphylaxis. Ann Allergy Asthma Immunol. 1999;83(1):25-26.
- Yamakoshi J, Sano A, Tokutake S, et al. Oral intake of proanthocyanidin-rich extract from grape seeds improves chloasma. Phytother Res 2004;18(11):895-899.
Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to . Selected references are listed below.