Grape seed extract
Grape seed extracts are industrial derivatives from whole grape seeds that have a great concentration of vitamin E, flavonoids, linoleic acid and phenolic OPCs. The typical commercial opportunity of extracting grape seed constituents has been for chemicals known as polyphenols having antioxidant activity in vitro.
Preliminary research 
Human case reports and results from basic research provide preliminary evidence that grape seed extract may affect heart diseases such as hypertension, high levels of blood cholesterol, platelet aggregation or inflammation. None of these possible effects has been confirmed in vivo.
A polyphenol contained in grape seeds is resveratrol, which is under study for its possible effect on cancer cell growth, proliferation or apoptosis, among other potential chemopreventive mechanisms.
Other preliminary research on disease models
- skin and wounds – OPCs induced vascular endothelial growth factor and accelerated healing of injured skin in mice
- teeth – seed phenolics may inhibit oral sugar metabolism and retard growth of certain bacteria that cause dental caries
- bones – grape seed extracts enhanced bone density and strength in experimental animals
- in vitro cancer studies – grape seed proanthocyanidins decreased tumor numbers and reduced the malignancy of papillomas
- ultraviolet damage – dietary proanthocyanidins are under study for mechanisms against carcinogenesis and sunscreen protection
- anti-viral effects
- liver function
- blood flow and fluid balance
There are 13 clinical trials (January, 2012) assessing potential effects of grape seed extracts on human diseases, such as breast cancer, blood estrogen levels in postmenopausal women, and coronary artery disease.
One clinical trial with adults having coronary disease or cardiac risk factors concluded that: "Four weeks of muscadine grape seed supplementation in subjects with increased cardiovascular risk did not produce a statistically significant increase in brachial flow-mediated vasodilation or a significant change in other biomarkers of inflammation, lipid peroxidation, or antioxidant capacity. However, the muscadine grape seed supplement did result in a significant increase in resting brachial diameter. The clinical significance of the effect on resting diameter is not yet established."
A meta-analysis of randomized controlled trials concluded that "grape seed extract appears to significantly lower systolic blood pressure and heart rate, with no effect on lipid or C-reactive protein levels."
The US National Center for Complementary and Alternative Medicine reported that oral administration of grape seed extract was well tolerated in people over 8 weeks. In one completed clinical trial, grape seed extract did not alleviate the hardening of breast tissue in female patients undergoing radiation therapy to treat breast cancer.
Dosage, precautions and interactions 
Oral grape seed extract is used in capsules or tablets usually containing 50 mg or 100 mg. Insufficient scientific information is known, however, about how long-term use of grape seed extract might affect health or any disease.
Side-effects and cautions, other NCCAM advisories.
- In general, grape seed extract is well tolerated when taken by mouth, although it is better tolerated when encapsulated, as its taste is bitter. It has been used safely for up to 8 weeks in clinical trials.
- Side-effects most often include headache, a dry, itchy scalp, dizziness, or nausea
- Interactions between grape seed extract and medicines or other supplements have not been carefully studied
Due to the possible action of proanthocyanidins on limiting platelet adhesion, grape seed extract may act as a blood-thinner, increasing clotting time.
Aromatase inhibitor 
- Bagchi, Debasis; Sen, Chandan K; Ray, Sidhartha D; Das, Dipak K; Bagchi, Manashi; Preuss, Harry G; Vinson, Joe A (2003). "Molecular mechanisms of cardioprotection by a novel grape seed proanthocyanidin extract". Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 523-524: 87–97. doi:10.1016/S0027-5107(02)00324-X. PMID 12628506.
- Vitseva, Olga; Varghese, Sonia; Chakrabarti, Subrata; Folts, John D; Freedman, Jane E (2005). "Grape Seed and Skin Extracts Inhibit Platelet Function and Release of Reactive Oxygen Intermediates". Journal of Cardiovascular Pharmacology 46 (4): 445–51. doi:10.1097/01.fjc.0000176727.67066.1c. PMID 16160595.
- Kundu, Joydeb Kumar; Surh, Young-Joon (2008). "Cancer chemopreventive and therapeutic potential of resveratrol: Mechanistic perspectives". Cancer Letters 269 (2): 243–61. doi:10.1016/j.canlet.2008.03.057. PMID 18550275.
- Gao, N.; Budhraja, A.; Cheng, S.; Yao, H.; Zhang, Z.; Shi, X. (2009). "Induction of Apoptosis in Human Leukemia Cells by Grape Seed Extract Occurs via Activation of c-Jun NH2-Terminal Kinase". Clinical Cancer Research 15 (1): 140–9. doi:10.1158/1078-0432.CCR-08-1447. PMC 2760842. PMID 19118041. Lay summary – BBC News (31 December 2008).
- Khanna, Savita; Venojarvi, Mika; Roy, Sashwati; Sharma, Nidhi; Trikha, Prashant; Bagchi, Debasis; Bagchi, Manashi; Sen, Chandan K (2002). "Dermal wound healing properties of redox-active grape seed proanthocyanidins". Free Radical Biology and Medicine 33 (8): 1089–96. doi:10.1016/S0891-5849(02)00999-1. PMID 12374620.
- Smullen, J.; Koutsou, G.A.; Foster, H.A.; Zumbé, A.; Storey, D.M. (2007). "The Antibacterial Activity of Plant Extracts Containing Polyphenols against Streptococcus mutans". Caries Research 41 (5): 342–9. doi:10.1159/000104791. PMID 17713333.
- Yahara, N; Tofani, I; Maki, K; Kojima, K; Kojima, Y; Kimura, M (2005). "Mechanical assessment of effects of grape seed proanthocyanidins extract on tibial bone diaphysis in rats". Journal of musculoskeletal & neuronal interactions 5 (2): 162–9. PMID 15951633.
- Katiyar, Santosh K. (2008). "Grape seed proanthocyanidines and skin cancer prevention: Inhibition of oxidative stress and protection of immune system". Molecular Nutrition & Food Research. 52 Suppl 1: S71–6. doi:10.1002/mnfr.200700198. PMC 2562900. PMID 18384090.
- Baliga, Manjeshwar S.; Katiyar, Santosh K. (2006). "Chemoprevention of photocarcinogenesis by selected dietary botanicals". Photochemical & Photobiological Sciences 5 (2): 243–53. doi:10.1039/b505311k. PMID 16465310.
- Su, X; d'Souza, DH (2011). "Grape seed extract for control of human enteric viruses". Applied and environmental microbiology 77 (12): 3982–7. doi:10.1128/AEM.00193-11. PMC 3131668. PMID 21498749.
- Nair, Madhavan P; Kandaswami, Chithan; Mahajan, Supriya; Nair, Harikrishna N; Chawda, RAM; Shanahan, Thomas; Schwartz, Stanley A (2002). "Grape seed extract proanthocyanidins downregulate HIV- 1 entry coreceptors, CCR2b, CCR3 and CCR5 gene expression by normal peripheral blood mononuclear cells". Biological Research 35 (3–4): 421–31. doi:10.4067/S0716-97602002000300016. PMID 12462994.
- Pan, Xinjuan; Dai, Yujie; Li, Xing; Niu, Nannan; Li, Wenjie; Liu, Fangli; Zhao, Yang; Yu, Zengli (2011). "Inhibition of arsenic induced-rat liver injury by grape seed exact through suppression of NADPH oxidase and TGF-β/Smad activation". Toxicology and Applied Pharmacology 254 (3): 323–31. doi:10.1016/j.taap.2011.04.022. PMID 21605584.
- University of Maryland Medical Center - Grape Seed
- Search results for grape seed extracts, ClinicalTrials.gov, a service of the US National Institutes of Health
- Mellen, Philip B.; Daniel, Kurt R.; Brosnihan, K. Bridget; Hansen, Kim J.; Herrington, David M. (2010). "Effect of Muscadine Grape Seed Supplementation on Vascular Function in Subjects with or at Risk for Cardiovascular Disease: A Randomized Crossover Trial". Journal of the American College of Nutrition 29 (5): 469–75. PMC 3313487. PMID 21504973.
- Feringa, Harm H.H.; Laskey, Dayne A.; Dickson, Justine E.; Coleman, Craig I. (2011). "The Effect of Grape Seed Extract on Cardiovascular Risk Markers: A Meta-Analysis of Randomized Controlled Trials". Journal of the American Dietetic Association 111 (8): 1173–81. doi:10.1016/j.jada.2011.05.015. PMID 21802563.
- Grape Seed Extract, Herbs at a Glance, US National Center for Complementary and Alternative Medicine
- Brooker, S; Martin, S; Pearson, A; Bagchi, D; Earl, J; Gothard, L; Hall, E; Porter, L et al. (2006). "Double-blind, placebo-controlled, randomised phase II trial of IH636 grape seed proanthocyanidin extract (GSPE) in patients with radiation-induced breast induration". Radiotherapy and Oncology 79 (1): 45–51. doi:10.1016/j.radonc.2006.02.008. PMID 16546280.
- Shanmuganayagam, Dhanansayan; Beahm, Mark R.; Osman, Hashim E.; Krueger, Christian G.; Reed, Jess D.; Folts, John D. (2002). "Grape Seed and Grape Skin Extracts Elicit a Greater Antiplatelet Effect When Used in Combination than When Used Individually in Dogs and Humans". The Journal of Nutrition 132 (12): 3592–8. PMID 12468593.
- Kijima, I.; Phung, S; Hur, G; Kwok, SL; Chen, S (2006). "Grape Seed Extract is an Aromatase Inhibitor and a Suppressor of Aromatase Expression". Cancer Research 66 (11): 5960–7. doi:10.1158/0008-5472.CAN-06-0053. PMID 16740737.
- Grape Seed Extract, from Herbs at a Glance (National Center for Complementary and Alternative Medicine, US National Institutes of Health)