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Grapeseed

 

Natural Standard Monograph, Copyright © 2014 (www.naturalstandard.com). Commercial distribution prohibited. This monograph is intended for informational purposes only, and should not be interpreted as specific medical advice. You should consult with a qualified health care professional before making decisions about therapies and/or health conditions.

Related Terms

  • 1,2-Di-O-acyl-3-O-beta-D-galactopyranosyl glycerols, 6'-O-acyldaucosterols, ActiVin®, activin, alpha-ylangene, amino acids, ampelopcin A, anthocyanins, astringin, betulin, betulinic acid, bioflavinols, black grape extract, black grape raisins, Bordeaux wine grape seed, cabernet franc, cabernet gernischt, cabernet sauvignon, caffeic acid, calzin, Carlos, catechin, chardonnay, Chilean black grape, chlorogenic acid, condensed tannins, coumaric acid, cyanidin-3,5-diglucoside, cyanidin-3-glucoside, cyaniding, daucosterol, delphinidin, drue kerne, emperor, Endotelon®, enocianina (Italian), epicatechin, epicatechin 3-O-gallate, epicatechin gallate, epigallocatechin, epsilon-viniferin, (E)-resveratrol 3,5-O-beta-diglucoside, extrait de pepins de raisin (French), fatty acids, fatty aliphatic aldehydes, ferulic acid, fisetin, flame seedless, flav-3-ols, flavanones, flavonoids, fragola, French red grape extract, French red wine grapes, fruit extracts, FruitSmart® Concord grape extract, gallic acid, gallocatechin, grape, grape complex, grape fruit, grape fruit skin, grape homogenate extracts, grape juice, grape marc, grape molasses, grape poamce, grape pomace extracts, grape rinds, grape seed, grape seed extract (GSE), grape seed oil, grape skin, grape skin extract, grapes, grapeseed, grapeseed oil, Grapple®, GSPE, IH636 grape seed proanthocyanidin, Indena's Grape Seed Standardized Extract®, iron, Isabel grape extract, Ison, kuromanin, leucoanthocyanidins, Leucoselect®-phytosome, malvidin, malvidin-3-acetylglucoside, malvidin 3-O-acetylglucoside, malvidin 3-O-acetylglucoside-4-vinylphenol, malvidin 3-O-acetylglucoside-pyruvate, malvidin 3-O-coumaroylglucoside-4-vinylphenol, malvidin 3-O-coumaroylglucoside-pyruvate, malvidin 3-O-glucoside, malvidin 3-O-glucoside-4-vinylphenol, malvidin 3-O-glucoside-pyruvate, Masquelier's Original OPCs®, melatonin, meoru, merlot, monomeric stilbenoid glucosides, morin, muscadine grape, muskat, myricetin, myrtillin, Nagano grape, Nagano purple grape, Niagara grape extract, Noble, nonhydrolyzable tannins, oenin, oleanolic acid, oleanolic aldehyde, oligostilbenes, oligomères procyanidoliques (French), oligomeric proanthocyanidins, OPCs, Panace-Vid 2000®, Parellada grape, pecmez, peomidin, peonidin-3-O-glucoside, peonidin-3-coumaryl-5-diglucoside, petite sirah, petunidin, petunidin-3-O-glucoside, phenylpropanoids, p-hydroxybenzoic acids, piceatannol, piceids, pine bark extract, polyphenol-based grape extract, polyphenolic grape extract, polyphenolic oligomers, polyphenols, Portuguese red grape skins, proanthocyanidin dimers, proanthocyanidins, procyanidin dimers, procyanidins, procyanidolic oligomers (PCOs), Pycnogenol®, quercetin, quercetin-3-arabinose, quercetin-3-rhamnose, raisins, red globe, red grape juice, red grape polyphenol extract, red grapes, red malaga, red muscadine grape, red wine polyphenols, Regrapex-R(R), resveratrol, resveratrol 3,4'-O-beta-diglucosides, resveratrol triacetate, Rkatsiteli grape oil, Rkatsiteli grapes, rutin, sauvignon blanc, serotonin, Shiraz grape berries, Shiraz red grape cultivar, sitosterols, sterols, stilbene, stilbenoid, strawberry grape, sultanas, Supreme, syringetin, syringetin 3-O-acetylglucoside, syringetin 3-O-glucoside, table grapes, tannins, tetrahydro-beta-carbolines, Thompson seedless, tocopherols, Traconol®, triterpenoid acids, Victoria grape, vineatrol, Vitaceae (family), Vitis amurensis, Vitis coignetiae, Vitis coignetiae Pulliat, vitis hybrid Bailey Alicant A, Vitis labrusca, Vitis × labruscana cv. Isabella, Vitis rotundifolia Michx., Vitis trifolia, Vitis vinifera L. cv. Grenache, Vitis vinifera L., Vitis vinifera L. cv. Chardonnay, Vitis vinifera L. cv. País, Vitis vinifera ssp. sativa, Vitis vinifera var. Nerello Mascalese, Vitis vinifera vars. Pinot Noir and Pinot Gris, vitisin A, vitisin B, white grape extract, wine grapes, (Z)-resveratrol 3,5-O-beta-diglucoside, (Z)-resveratrol 3,5,4'-O-beta-triglucoside.
  • Combination product examples: Cellasene (grape seed oil, Gingko biloba, sweet clover, seaweed, lecithin, and evening primrose oil); Imedeen Time Perfection (a mixture of BioMarine Complex, grape seed extract, tomato extract, and vitamin C); Seresis (carotenoids (beta-carotene and lycopene), vitamins C and E, selenium, and proanthocyanidins).
  • Note: Pycnogenol® is a patented nutrient supplement extracted from the bark of the European coastal pine Pinus maritima. Pycnogenol® consists of flavonoids, catechins, procyanidins, and phenolic acids, which are the same constituents found in grape seed, but not the same supplement. For more information on Pycnogenol®, see the individual monograph.
  • Wine is a fermented grape product and is discussed in more detail in a separate monograph.
  • The focus of this monograph is all parts of the plant Vitis vinifera, and other species of grape are not specifically discussed. However, in many cases, the species of grape is unclear.
  • The focus of this monograph is all parts of the plant Vitis vinifera. Specific information on resveratrol may be found in a separate bottom line.

Background

  • Grape leaves, sap, seed, and fruit have been used medicinally since the Greek empire. Different parts of the plant have been used traditionally for conditions such as skin and eye irritation, bleeding, varicose veins, diarrhea, cancer, and smallpox.
  • Interest in grape products increased with the recognition of the potential heart-protective effects of wine consumption in French men consuming a high-fat diet. Grape has been shown to possess antioxidant, blood clot-preventing, and cholesterol-lowering properties.
  • The antioxidant properties of grape seed oligomeric proanthocyanidins (OPCs) make these extracts potential therapies for many diseases. Research has documented the effectiveness of grape seed OPCs for damaged blood vessel valves or weak blood vessels, diabetic retinopathy (eye damage), edema (fluid accumulation) in the arms and legs, and high cholesterol. OPCs appear to be well tolerated, with few side effects noted in the available research. However, long-term studies assessing safety are lacking.

Evidence

 

Uses based on scientific evidence 

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 professional.

Grade* 

Chronic venous insufficiency (damaged vein valves) 

High-quality research reports that that grape seed OPCs may reduce the symptoms of poor circulation in leg veins. Furthermore, red leaf vine extract may be effective for preventing and managing chronic venous insufficiency.

A 

Edema (swelling) 

Research shows that grape seed ingredients may speed the reduction of swelling after injury, including surgery. Larger, high quality studies are needed to confirm these results.

A 

Diabetic retinopathy (eye problems) 

Diabetic retinopathy is a disease of the small blood vessels in the eye's retina. Early research using OPCs and the brand name product Endotelon® has shown beneficial effects in stopping disease progression. Additional research is needed in this area.

B 

Vascular fragility 

Early research suggests that ingredients from grape seed may make small blood vessels less fragile. Additional research is needed in this area.

B 

Agitation in dementia 

Grape seed oil is a popular carrier oil used in aromatherapy. There is mixed evidence as to whether aromatherapy may benefit agitation in dementia. Additional research is needed in this area.

C 

Antioxidant 

Studies have found grape and grape products to contain antioxidants. Antioxidants may protect against heart disease. Additional research is needed in this area.

C 

Athletic performance 

Early research suggests grape extract may increase power in athletes. Additional research is needed in this area.

C 

Chemotherapy side effects 

Grape lacks supportive evidence for improving nausea and vomiting from chemotherapy. Additional research is needed in this area.

C 

Coronary artery disease 

Early research suggests grape juice may benefit blood flow. More high-quality studies are needed to draw a conclusion.

C 

Heart disease prevention 

Early research suggests that grape may benefit blood pressure, cholesterol, and blood flow. Additional research is needed in this area.

C 

High blood pressure 

Grape extract may have a beneficial effect on blood pressure and heart rate. Additional research is needed in this area.

C 

High cholesterol 

Early research suggests OPCs may reduce LDL ("bad") cholesterol. Grape may also possess antioxidant properties and reduce clogged arteries. Additional research is needed in this area.

C 

Immune function 

Grape juice may increase the number of immune system cells. Additional research is needed in this area.

C 

Liver disease 

Grape seed extract may improve some symptoms of liver disease. Additional research is needed in this area.

C 

Melasma (dark skin spots) 

Melasma is a skin discoloration that may occur due to hormonal imbalances. Antioxidants are thought to improve skin color, and grape seed extract is thought to have antioxidant activity. Additional research is needed in this area.

C 

Memory 

Grape juice may benefit verbal learning and memory in the elderly. Additional research is needed in this area.

C 

Pancreatitis (inflamed pancreas) 

Grape seed may reduce stomach pain associated with an inflamed pancreas. Additional research is needed in this area.

C 

Premenstrual syndrome (PMS) 

Early research shows positive results on grape seed for PMS symptoms. Additional research is needed in this area.

C 

Radiation injuries 

Grape seed contains OPCs, which may have antioxidant properties. Antioxidants have potential radioprotective properties. Although initial results show a lack of benefit, larger studies are needed.

C 

Skin aging 

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 research is needed in this area.

C 

Vision problems 

Grape may improve sensitivity to light and glare. Additional research is needed in this area.

C 

Weight loss 

Early research suggests that grape juice may reduce waist circumference. Additional research is needed in this area.

C 

Allergies 

Grape seed has been used to treat immune system disorders due to its antioxidant effects. However, research on grape seed's effect on allergies shows mixed results. Additional research is needed in this area.

D 

 

*Key to grades: 

A: Strong scientific evidence for this use;
B: Good scientific evidence for this use;
C: Unclear scientific evidence for this use;
D: Fair scientific evidence against this use (it may not work);
F: Strong scientific evidence against this use (it likely does not work).

For full grading rationale, click here.

Uses based on tradition or theory 

The below uses are based on tradition or scientific theories. 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 health care professional

AIDS/HIV, Alzheimer's disease, antibacterial, antidepressant, antifungal, antimicrobial, antineoplastic, antiplatelet, antivenom, antiviral, appetite suppressant, arthritis, asthma, astringent, attention deficit-hyperactivity disorder (ADHD), blood thinner, blood vessel dilation (relaxation), body fat reducer (cellulite), bruising, cachexia (weight loss and wasting from some diseases), cholera (small intestine infection), chronic fatigue syndrome, circulatory/blood flow disorders, cognition, colds, connective tissue disorders, constipation, corneal abrasion, cough, cramps (menstrual), dental conditions, detoxification, diabetes, diabetic neuropathy (nerve damage), diarrhea, diuretic (increased urine), energy, estrogenic agent (mimics the effects of estrogen), exercise recovery, food preservative, gastrointestinal disorders, glaucoma (eye disorder), hemorrhage, hemorrhoids, inflammation, kidney toxicity, liver damage, longevity/anti-aging, lymphedema (fluid buildup), myocardial ischemia/reperfusion injury (altered blood flow to the heart), nausea, neuroprotection (nerve protection), osteoporosis, pain, painful menstruation, Parkinson's disease, photoprotection, psoriasis, respiratory tract infections, scurvy, shock, skin care, skin diseases, skin irritation, smallpox, sore throat, stroke, tonic, varicose veins, vascular disorders (prevention in diabetics), well-being, wound healing.


Safety

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 professional before starting a new therapy. Consult a healthcare professional immediately if you experience side effects.

Allergies

  • Avoid with known allergy or sensitivity to grape (Vitis spp.), any of its constituents, or other members of the Vitaceae family.
  • Cases of allergic reactions to grape, grape products, oligomeric proanthocyanidins (OPCs), grape skin extract, or grape color extract have been reported. Cases of anaphylactic shock after consumption of grapes or grape products have been reported. Crossover allergies to apples, bananas, cherries, and peaches have been reported. Occupational allergies to grape pollen have been reported.

Side Effects and Warnings

  • Grape and grape products are likely safe when consumed by people without a grape allergy in amounts naturally found in foods. Grape and grape products are likely safe when used by healthy adults in suggested doses for medical purposes.
  • Grape may lower blood sugar levels. Caution is advised in people with diabetes or hypoglycemia and in those taking drugs, herbs, or supplements that affect blood sugar. Blood glucose levels may need to be monitored by a qualified healthcare professional, including a pharmacist, and medication adjustments may be necessary.
  • Grape may increase the risk of bleeding. Caution is advised in people with bleeding disorders or taking drugs that may increase the risk of bleeding. Dosing adjustments may be necessary.
  • Use cautiously in people taking agents metabolized by cytochrome P450 enzymes, agents that prevent blood clots such as warfarin, aspirin, nonsteroidal anti-inflammatory drugs, or agents that prevent platelet aggregation. Use cautiously in people on methotrexate therapy or in combination with vitamin C.
  • Use cautiously in people with blood pressure disorders, clotting disorders, diabetes, skin conditions, gastrointestinal disorders (including bowel obstruction), psychiatric conditions, or breathing problems.
  • Use cautiously when grape seed extract is used above normal dietary levels by pregnant or breastfeeding women, or by children.
  • Avoid with known allergy or sensitivity to grape (Vitis spp.), any of its constituents, or other members of the Vitaceae family.
  • Avoid in people with bleeding disorders or people with active bleeding problems, such as peptic ulcers or intracranial bleeding.
  • Grape may also cause acne, acute hepatitis, arthritis symptoms, asthma, back pain, bowel obstruction, breathing problems, bruising, cardiac arrest, changes in platelets, common cold, cough, diarrhea, dizziness, dry and itchy scalp, eczema, feeling unwell, gas, headache, high blood pressure, high cholesterol, hives, increased blood sugar, increased methotrexate toxicity, increased urination, indigestion, infection of the hair follicles, inflamed veins, inflammation of the stomach lining, itchy skin, nausea, rash, runny nose, shortness of breath, sleep problems, sore throat, stomach discomfort, swelling, vaginal bleeding, vertigo (dizziness), and widening of blood vessels.
  • Note: Discontinue use of grape products or grape parts, at levels greater than those commonly found in the diet, at least two weeks prior to surgery or a dental procedure, in order to prevent bleeding.
  • Note: Wash grapes well before eating to remove pesticide residues. According to secondary sources, grapes are on a list of the top 12 fruits and vegetables to buy organic.

Pregnancy and Breastfeeding

  • Use grape seed extract cautiously in amounts greater than those normally found in food, due to the lack of efficacy and safety information.
  • Resveratrol, a chemical found in grape, may increase calcium levels and induce uterine contractions
  • There is a lack of scientific evidence on the use of grape during pregnancy or lactation.

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 professional before starting a new therapy.

Interactions with Drugs

  • Grape may lower blood sugar levels. Caution is advised when using medications that may also lower blood sugar. People taking drugs for diabetes by mouth or insulin should be monitored closely by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.
  • Grape 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, antiplatelet drugs such as clopidogrel (Plavix®), and nonsteroidal anti-inflammatory drugs such as ibuprofen (Motrin®, Advil®) or naproxen (Naprosyn®, Aleve®).
  • Grape 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 decreased in the blood, and the intended effects may be reduced. People taking any medications should check the package insert and speak with a qualified healthcare professional, including a pharmacist, about possible interactions.
  • Grape may cause low blood pressure. Caution is advised in people taking drugs that lower blood pressure.
  • Because grape contains estrogen like chemicals, the effects of other agents believed to have estrogen-like properties may be altered.
  • Grape may also interact with agents for cancer, diabetes, gout, obesity, or osteoporosis; agents for diarrhea, nausea, or vomiting; agents for the brain, heart, skin, or teeth; agents for excess uric acid; agents that alter immune function; agents that increase sensitivity to light; agents that reduce pain or inflammation; agents that widen blood vessels; agents toxic to the liver; angiotensin-converting enzyme (ACE) inhibitors; antibiotics; antidepressants; antifungals; antivirals; cholesterol-lowering agents; cyclooxygenase (COX)-2 inhibitors; cyclosporin A; doxorubicin (Adriamycin); folate analogs; insulin preparations; methotrexate; phenacetin; snake venom antidote; and wound-healing agents.

Interactions with Herbs and Dietary Supplements

  • Grape may lower blood sugar levels. Caution is advised when using herbs or supplements that may also lower blood sugar. Blood glucose levels may require monitoring, and doses may need adjustment.
  • Grape 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, and fewer cases with garlic and saw palmetto. Numerous other agents may theoretically increase the risk of bleeding, although this has not been proven in most cases.
  • Grape 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 may become too low in the blood. It may also alter the effects that other herbs or supplements potentially may have on the P450 system.
  • Grape may cause low blood pressure. Caution is advised in people taking herbs or supplements that lower blood pressure.
  • Because grape contains estrogen-like chemicals, the effects of other agents believed to have estrogen-like properties may be altered.
  • Grape may also interact with antibacterials; antidepressants; antifungals; antioxidants; antivirals; cholesterol-lowering herbs and supplements; chromium; copper; cyclooxygenase (COX)-2 inhibitors; estrogens; fish oil; folate; green tea extract; herbs and supplements for cancer, gout, obesity, or osteoporosis; herbs and supplements for diarrhea, nausea or vomiting; herbs and supplements for the brain, heart, skin or teeth; herbs and supplements that alter immune function or blood sugar; herbs and supplements that that increase sensitivity to light; herbs and supplements that reduce pain or inflammation; herbs and supplements that widen blood vessels; herbs and supplements toxic to the liver; iron; Lactobacillus acidophilus; nisin; nitric oxide; probiotics; resveratrol; Scutellaria baicalensis; snake venom antidote; tartaric acid; vitamins C and E; wound-healing herbs and supplements; and zinc.

Authors

Selected References

Natural Standard developed the above evidence-based information based on a systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

  1. Barona, J., Aristizabal, J. C., Blesso, C. N., Volek, J. S., and Fernandez, M. L. Grape polyphenols reduce blood pressure and increase flow-mediated vasodilation in men with metabolic syndrome. J Nutr 2012;142(9):1626-1632.
  2. Barona, J., Blesso, C. N., Andersen, C. J., Park, Y., Lee, J., and Fernandez, M. L. Grape consumption increases anti-inflammatory markers and upregulates peripheral nitric oxide synthase in the absence of dyslipidemias in men with metabolic syndrome. Nutrients. 2012;4(12):1945-1957.
  3. De, Groote D., Van, Belleghem K., Deviere, J., Van, Brussel W., Mukaneza, A., and Amininejad, L. Effect of the intake of resveratrol, resveratrol phosphate, and catechin-rich grape seed extract on markers of oxidative stress and gene expression in adult obese subjects. Ann Nutr Metab 2012;61(1):15-24.
  4. Dohadwala, M. M., Hamburg, N. M., Holbrook, M., Kim, B. H., Duess, M. A., Levit, A., Titas, M., Chung, W. B., Vincent, F. B., Caiano, T. L., Frame, A. A., Keaney, J. F., Jr., and Vita, J. A. Effects of Concord grape juice on ambulatory blood pressure in prehypertension and stage 1 hypertension. Am J Clin.Nutr. 2010;92(5):1052-1059.
  5. Feringa, H. H., Laskey, D. A., Dickson, J. E., and Coleman, C. I. The effect of grape seed extract on cardiovascular risk markers: a meta-analysis of randomized controlled trials. J Am Diet.Assoc. 2011;111(8):1173-1181.
  6. Hashemi, M., Kelishadi, R., Hashemipour, M., Zakerameli, A., Khavarian, N., Ghatrehsamani, S., and Poursafa, P. Acute and long-term effects of grape and pomegranate juice consumption on vascular reactivity in paediatric metabolic syndrome. Cardiol Young. 2010;20(1):73-77.
  7. Krikorian, R., Nash, T. A., Shidler, M. D., Shukitt-Hale, B., and Joseph, J. A. Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment. Br J Nutr. 2010;103(5):730-734.
  8. Ndiaye, M., Philippe, C., Mukhtar, H., and Ahmad, N. The grape antioxidant resveratrol for skin disorders: promise, prospects, and challenges. Arch.Biochem.Biophys. 4-15-2011;508(2):164-170.
  9. Pasinetti, G. M. Novel role of red wine-derived polyphenols in the prevention of Alzheimer's disease dementia and brain pathology: experimental approaches and clinical implications. Planta Med 2012;78(15):1614-1619.
  10. Rabe, E., Stucker, M., Esperester, A., Schafer, E., and Ottillinger, B. Efficacy and tolerability of a red-vine-leaf extract in patients suffering from chronic venous insufficiency--results of a double-blind placebo-controlled study. Eur.J Vasc.Endovasc.Surg. 2011;41(4):540-547.
  11. Reddy, K. K., Grossman, L., and Rogers, G. S. Common complementary and alternative therapies with potential use in dermatologic surgery: risks and benefits. J Am Acad.Dermatol 2013;68(4):e127-e135.
  12. Rowe, C. A., Nantz, M. P., Nieves, C., Jr., West, R. L., and Percival, S. S. Regular consumption of Concord grape juice benefits human immunity. J Med Food 2011;14(1-2):69-78.
  13. Song, P., Zhang, R., Wang, X., He, P., Tan, L., and Ma, X. Dietary grape-seed procyanidins decreased postweaning diarrhea by modulating intestinal permeability and suppressing oxidative stress in rats. J Agric.Food Chem 6-8-2011;59(11):6227-6232.
  14. Tome-Carneiro, J., Gonzalvez, M., Larrosa, M., Garcia-Almagro, F. J., Aviles-Plaza, F., Parra, S., Yanez-Gascon, M. J., Ruiz-Ros, J. A., Garcia-Conesa, M. T., Tomas-Barberan, F. A., and Espin, J. C. Consumption of a grape extract supplement containing resveratrol decreases oxidized LDL and ApoB in patients undergoing primary prevention of cardiovascular disease: a triple-blind, 6-month follow-up, placebo-controlled, randomized trial. Mol.Nutr Food Res 2012;56(5):810-821.
  15. Tome-Carneiro, J., Gonzalvez, M., Larrosa, M., Yanez-Gascon, M. J., Garcia-Almagro, F. J., Ruiz-Ros, J. A., Garcia-Conesa, M. T., Tomas-Barberan, F. A., and Espin, J. C. One-year consumption of a grape nutraceutical containing resveratrol improves the inflammatory and fibrinolytic status of patients in primary prevention of cardiovascular disease. Am J Cardiol. 8-1-2012;110(3):356-363.