Grape seed extracts have compounds called procyanidolic oligomers (PCOs). Other sources of PCOs are berries, green and black teas, and red wine.
   PCOs are powerful antioxidants, perhaps much greater than vitamins C and E. They also inhibit a number of enzymes that degrade connective tissue such as elastase, collagenase, and hyaluronidase.

Grape Seed Extract supplement, 100 mg
Joint Power Rx with Grape Seed Extract
Grape Seed Extract is a natural plant product made from the grape seed (or pip). Grape Seed Extract is rich in procyanidins, a special class of water-soluble bioflavonoids which are excellent free radical scavengers.

Grape Seed Extract Supplement Facts
Grape Seed Extract - 100 mg *

Suggested Use: 1 to 2 grape seed extract tablets a few times a week, or as recommended by your health care professional.

* Grape seed extract daily value not established.

Click here to buy Grape Seed extract, Joint Power Rx, or to sign up to a FREE newsletter
Subscribe to a FREE Supplement Research Update newsletter. Twice a month we email a brief abstract of several studies on various supplements and natural medicine topics - including grape seed extract - and their practical interpretation by Ray Sahelian, M.D.

Joint Power Rx with Grape Seed Extract, Formulated by Ray Sahelian, M.D.
Because joint pain is so debilitating, Glucosamine and Chondroitin alone are not enough. This powerful formula includes several additional herbal extracts and nutrients that play a role in joint health.  

Benefit of Grape Seed extract
The primary clinical indications for grape seed extract are the treatment of such vascular disorders as venous insufficiency and capillary fragility and possibly retinal maladies such as diabetic retinopathy and macular degeneration. PCOs may improve night vision.

Additional health benefits of Grape Seed extract
Moderately high amounts of grape seed extract may blunt salt-sensitive hypertension.
Grape seed extract may be helpful as an antioxidant in smokers.

According to one study, grape seed extract does not provide relief for symptoms such as stuffy nose, sneezing and itchy, and watery eyes.

Grape Seed extract and Hypertension
Cardiovascular researchers at UC Davis, School of Medicine, completed the first human clinical trial to study the benefits of grape seed extract on patients with high blood pressure. The one month study was done on 24 male and female patients diagnosed with metabolic syndrome, which is a combination of factors that add up to high risk for heart disease, including elevated blood pressure, excess abdominal body weight, high blood cholesterol fats, and high blood sugar. The patients were divided into three groups of eight. The first group received a placebo while the second and third groups received 150 mgs and 300 mgs, respectively, of a grape seed extract developed and made by Polyphenolics, a division of Constellation Wine US. All participants' blood pressure was automatically measured and recorded for 12 hours after grape see extract ingestion. Participants in the two groups receiving grape seed extract experienced an average drop in systolic pressure or 12 mm and diastolic pressure 8 mm compared to placebo.
     Dr. Sahelian says: This is encouraging news regarding the role of grape seed extract and blood pressure. It would seen a good idea to take 100 mg a day of grape seed extract with medical supervision and monitoring of BP.

Skin cancer and grape skin extract
Chemicals found in grape seeds may help ward of skin cancer due to regular exposure to the sun. Researchers from the University of Alabama, Birmingham exposed hairless mice to ultraviolet-light. Some of the mice they fed a standard diet supplemented with grape seed proanthocyanidins, while control mice were fed a standard diet without this supplement. Dietary supplementation with grape seed extract inhibited light-induced carcinogenesis, study. Mice supplemented with grape seed extract had up to 65 fewer skin cancer tumors than control mice did. Moreover, the tumors seen in grape seed extract -supplemented mice were smaller than those seen in the control mice. Grape seed extracts appear to inhibit suppression of the immune system caused by ultraviolet light. Grape seed extract has antioxidant activity, and UV-induced oxidative stress has been linked to the induction of skin cancers.

Grape Seed extract availability
Grape Seed extract is sold in various extract potencies, including 95 percent proanthocyanidins or 95 percent polyphenols.

Grape seed extract side effects
Grape seed extract side effects have not been reported in the medical literature, but very few human studies have been done. In one study with cancer patients given radiation therapy and grape seed extract 100 mg three times a day orally for 6 months, no major side effects were reported.

Grape Seed Research Update
Grape seed extract prevents H(2)O(2)-induced chromosomal damage in human lymphoblastoid cells.
Biol Pharm Bull. 2004 Sep;27(9):1459-61.
We examined the effects of grape seed extract on chromosomal damage in two ways; induction on its own and prevention against treatment of reactive oxygen species. The Grape seed extract was composed of 89% proanthocyanidin with a degree of polymerization ranging from 2 to 15. Grape seed extract did not induce chromosomal damage in WIL2-NS cells. In contrast, pretreatment with Grape seed extract dose-dependently prevented H(2)O(2)-induced chromosomal damage. A similar preventive effect of Grape seed extract was not detected in tert-butyl hydroperoxide-induced damage even at 5 mg/l. In a cell free system, Grape seed extract (<5 mg/l) directly scavenged H(2)O(2), but produced slight amounts of H(2)O(2) at higher concentrations (>50 mg/l). These results suggest that Grape seed extract is not genotoxic, but rather has an antigenotoxic effect against H(2)O(2) via direct scavenging action of H(2)O(2).

Oral intake of proanthocyanidin-rich extract from grape seeds improves chloasma.
Phytother Res. 2004 Nov;18(11):895-9.
Chloasma (melasma), an acquired hypermelanosis, is often recalcitrant to various treatments and an amenable, as well as safe, pigment-reducing modality is needed. We investigated that the reducing effect of proanthocyanidins on chloasma in a one-year open design study. Proanthocyanidin-rich grape seed extract was orally administered to 12 Japanese woman candidates with chloasma for 6 months between August 2001 and January 2002 and to 11 of these 12 for 5 months between March and July 2002. Clinical observation, L* value (lightening) and melanin index, and size (length and width) measurements of chloasma were performed throughout the study period. The first 6 months of grape seed extract intake improved or slightly improved chloasma in 10 of the 12 women and following 5 months of intake improved or slightly improved chloasma in 6 of the 11 candidates. L* values also increased after grape seed extract intake. Melanin-index significantly decreased after 6 months of the intake, and also decreased at the end of study. Grape seed extract is effective in reducing the hyperpigmentation of women with chloasma. The beneficial effects of grape seed extract was maximally achieved after 6 months and these was no further improvement after this period. The latter grape seed extract intake for 5 months may prevent chloasma from becoming worse prior to the summer season. Grape seed extract is safe and useful for improving melasma.

Supplementation with grape seed polyphenols results in increased urinary excretion of 3-hydroxyphenylpropionic Acid, an important metabolite of proanthocyanidins in humans.
J Agric Food Chem. 2004 Aug 25;52(17):5545-9.
Grape seed extract provides a concentrated source of polyphenols, most of which are proanthocyanidins. Polymeric proanthocyanidins are poorly absorbed in the small intestine of humans, and exposure may result from metabolism to phenolic acids by colonic bacteria. Any biological effects of proanthocyanidins may be due to the phenolic acid metabolites. Several phenolic acids have been identified as proanthocyanidin metabolites, but these may be derived from a range of other dietary sources. The aim of this study was to determine if 24-h urinary excretion of specific phenolic acids increased significantly and consistently following regular supplementation with grape seed extract. In a randomized, double-blind placebo-controlled trial, 69 volunteers received grape seed extract (1000 mg/day total polyphenols) or placebo for 6 weeks. Supplementation with grape seed polyphenols resulted in a consistent increase in the excretion of 3-hydroxyphenylpropionic acid (3-HPP, P < 0.001) and 4-O-methylgallic acid (P < 0.001) and a less consistent increase in the excretion of 3-hydroxyphenylacetic acid (P = 0.002). The observed increase in 3-HPP is in line with the suggestion that this compound is a major phenolic acid breakdown product of proanthocyanidin metabolism in vivo.

Neuroprotective effects of grape seed extract on neuronal injury by inhibiting DNA damage in the gerbil hippocampus after transient forebrain ischemia.
Life Sci. 2004 Sep 3;75(16):1989-2001.
Grape seed extract possess cardioprotective abilities by functioning as in vivo antioxidants and by virtue of their ability to directly scavenge ROS including hydroxyl and peroxyl radicals. In the present study, we investigated the neuroprotective effects of grape seed extract in the gerbil hippocampus after 5 min transient forebrain ischemia. Neuronal cell density in grape seed extract-treated ischemic animals was significantly increased as compared with vehicle-treated ischemic animals 4 days after ischemic insult. In the grape seed extract-treated groups, about 60% of pyramidal cells of the sham-operated group were stained with cresyl violet 4 days after ischemic insult. In this study, we found that grape seed extract had neuroprotective effects on neuronal injury by inhibiting DNA damage in the CA1 region after ischemia. In vehicle-treated groups, 8-hydroxy-2'-deoxyguanosine (8-OHdG) immunoreactivity was significantly changed time-dependently, whereas the immunoreactivity in the grape seed extract-treated group was similar to the sham-operated group. In addition, we confirmed that astrocytes and microglia did not show significant activation in the CA1 region 4 days after ischemia-reperfusion, because many CA1 pyramidal cells were not damaged. Therefore, these results suggest that grape seed extract can protect ischemic neuronal damage by inhibiting DNA damage after transient forebrain ischemia.

Grape seed extract affects proliferation and differentiation of human intestinal Caco-2 cells.
J Agric Food Chem. 2004 Jun 2;52(11):3301-8.
The effect of daily contact of a grape seed extract (GSE) on Caco-2 cell proliferation and differentiation was investigated. Grape seed extract at 400 mg/L was added to Caco-2 cells for 2 h a day after successive incubation in saliva, gastric, and pancreatic media. When applied at the beginning of the cell culture, Grape seed extract triggered inhibition of cell growth associated with a possible cytotoxic reaction. On the other hand, when the treatment was applied to confluent cells, treated cells displayed a higher protein content than control cells and a more developed brush border, with taller and denser microvilli. These observations were accompanied by stimulation of alkaline phosphatase activity, especially at day 5 postconfluency, with a 2.2-fold increase in comparison with the control. On the other hand, aminopeptidase N activity was inhibited throughout the differentiation period in Grape seed extract-treated cells to reach 28.8% of control cell activity on day 30. Grape seed extract did not affect either sucrase-isomaltase activity or cytoplasmic lactate dehydrogenase (LDH) activity, which otherwise appeared to be a good cellular marker. Grape seed extract treatment of Caco-2 cells thus inhibited their proliferation from seeding onward and stimulated both proliferation and differentiation after confluency.

The effect of grape-seed extract on 24 h energy intake in humans.
Eur J Clin Nutr. 2004 Apr;58(4):667-73.
OBJECTIVE: Since grape-seed extract has been shown to stimulate lipolysis in vitro and reduce food intake in rats, we assessed the efficacy of grape-seed extract with respect to energy intake (EI) and satiety. DESIGN: In a randomized, placebo-controlled, double-blind, cross-over study, 51 subjects (age 18-65 y, body mass index 22-30 kg/m2) ate an ad libitum lunch and dinner twice in the University Restaurant for 3 days. Standard breakfasts and snacks were provided. Supplements were taken 30-60 min prior to each meal. RESULTS: In the total study population, no difference in 24 h EI was found between the grape-seed extract and placebo. However, in the subgroup of subjects (n=23) with an energy requirement > or =the median of 7.5 MJ/day, EI was reduced by 4% (DeltaEI 352.1 kJ/24 h, P=0.05) after grape-seed extract compared to placebo treatment. Meanwhile, there were no significant differences in macronutrient composition, attitude towards eating, satiety, mood or tolerance. CONCLUSIONS: Grape seed reduced 24 h EI, with on average 4% in subjects who had an energy requirement > or =7.5 MJ/day, without further effects on satiety, mood or tolerance. These findings suggest that grape seed could be effective in reducing 24 h EI in normal to overweight dietary unrestrained subjects, and could, therefore, play a significant role in body-weight management.

Effect of a standardized grape seed extract on low-density lipoprotein susceptibility to oxidation in heavy smokers.
Vigna GB. University of Ferrara, Ferrara, Italy.
Metabolism. 2003 Oct;52(10):1250-7.
The aim of our study was to evaluate the effect of a standardized formulation of a polyphenolic extract of grapes (Leucoselect-Phytosome) on low-density lipoprotein (LDL) susceptibility to oxidation in a group of heavy smokers. A randomized, double-blind, crossover study was undertaken in 24 healthy male heavy smokers, aged > or = 50 years. Enrolled subjects were given 2 capsules twice daily for 4 weeks (phase 1). Each capsule contained 75 mg of a grape procyanidin extracts and soy-phosphatidlcholine or placebo consisiting of 75 mg lactose and soy-phosphatidlcholine. A wash out period of 3 weeks was then followed by 4 weeks of the opposite treatment (phase 2). Blood samples were taken at baseline and at the end of each phase and assayed for plasma lipids and LDL susceptibility to oxidation. Compliance was good, and no adverse effects were recorded. Subjects did not show significant modification of total cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C) and LDL-C during LP treatment. Among oxidative indices, thiobarbituric acid reactive substances (TBARS) concentration was significantly reduced in subjects taking grape seed extract, and the lag phase prolonged compared with placebo and basal values. The antioxidant potential of grape seed extract polyphenols may prove effective in a model of oxidative stress (smoking); however more investigational data are needed before use in wider clinical settings.

Polyphenolics in grape seeds-biochemistry and functionality.
J Med Food. 2003 Winter;6(4):291-9.
Grape seeds are waste products of the winery and grape juice industry. These seeds contain lipid, protein, carbohydrates, and 5-8% polyphenols depending on the variety. Polyphenols in grape seeds are mainly flavonoids, including gallic acid, the monomeric flavan-3-ols catechin, epicatechin, gallocatechin, epigallocatechin, and epicatechin 3-O-gallate, and procyanidin dimers, trimers, and more highly polymerized procyanidins. Grape seed extract is known as a powerful antioxidant that protects the body from premature aging, disease, and decay. Grape seeds contains mainly phenols such as proanthocyanidins (oligomeric proanthocyanidins). Scientific studies have shown that the antioxidant power of proanthocyanidins is 20 times greater than vitamin E and 50 times greater than vitamin C. Extensive research suggests that grape seed extract is beneficial in many areas of health because of its antioxidant effect to bond with collagen, promoting youthful skin, cell health, elasticity, and flexibility. Other studies have shown that proanthocyanidins help to protect the body from sun damage, to improve vision, to improve flexibility in joints, arteries, and body tissues such as the heart, and to improve blood circulation by strengthening capillaries, arteries, and veins. The most abundant phenolic compounds isolated from grape seed are catechins, epicatechin, procyanidin, and some dimers and trimers.

Grape seed extract activates Th1 cells in vitro.
Clin Diagn Lab Immunol 2002 Mar;9(2):470-6
Although flavonoids manifest a diverse range of biological activities, including antitumor and antiviral effects, the molecular mechanisms underlying these activities await elucidation. We hypothesize that the flavonoid constituents of a proprietary grape seed extract that contains procyandins exert significant antiviral and antitumor effects, by inducing production of the Th1-derived cytokine gamma interferon (IFN-gamma) by peripheral blood mononuclear cells) from healthy donors. Our results show that grape seed extract significantly induced the transcription of IFN-gamma mRNA as demonstrated by reverse transcription-PCR but had no effect on the Th2-derived cytokine interleukin-6. The enhancing effect of grape seed extract on IFN-gamma expression was further supported by a concomitant increase in the number of cells with intracytoplasmic IFN-gamma as well as the synthesis and secretion of IFN-gamma. Our results demonstrate that the potentially beneficial immunostimulatory effects of grape seed extract may be mediated through the induction of IFN-gamma.

Grape seed emails
Q. What can you tell me about Grape seed oil ?
     A. We have not had a chance to evaluate the benefits of grape seed oil.

Q. I am wondering if grape seed extract supplement should be standardized to 95% polyphenols. I notice that many herbal products do not seem to be standardized. Thanks for your time and your newsletter is right on.
     A. Since there are no long term human studies with grape seed extract, it is anybody's guess as to the ideal extract potency. Also, there are few herbs that have been studied in an accepted standardized form. Little is known as to whether a certain standardized extract is better than the whole herb or a different extract potency. With all these uncertainties, no definite guidelines can be given.

Q. Grapeseed extract !!!! My husband and I both have tended to suffer from frequent morning migraines. We do not drink alcohol. One Grapeseed extract before bedtime has cut these occurrences at least 90% or more. It's been miraculous. I first discovered this unmistakable phenomenon and got my husband on them and now we make sure we take it before bedtime. "Did you take your Grapeseed extract? I started taking them because he read somewhere that it helped promote better sleep, a problem more for me than him and it does that as well. Like I said, the biggest unexpected boon is the migraine prevention. We both had true migraines. All day and very debilitating and a ton of over the counter pain killer sometimes just barely took the edge off (if lucky). Mine were generally gone by evening, but I was losing a day at least 2 times a week. His could go on into the next day. So we're healthier because now we are not pouring Ibuprofen, aspirin and acetaminophen into our systems on a regular basis. On the rare occasion that a migraine starts to happen, we have both found that 1 advil (instead of the previous 4) plus 1 grapeseed banishes it.
Once in while, up to 3 or 4 grapseed extract pills works alone once a migraine has grabbed hold but not usually. Then the 1 or 2 grapeseed and 1 advil works. The best thing is prevention, so it is an indispensible herb for us both before bed.
   A. This is interesting. What brands were they, was it only grape seed extract or combined with other herbs?
      Q. Spring Valley and the CVS Brand are 2 we've used recently. There are other ingredients in the last 2 or so bottles we've purchased, but I have received the same effect from plain grapeseed extract which was what I initially used. So many brands now have other ingredients added that at first we wondered if it would work the same. It does. Right at the moment the brand is: Spring Valley Grapeseed plus Resveratol. Purchased at Walmart. Selenium - 15mcg, Grapeseed Extract - seed and skin standardized to contain polyphenols - 50mg. Antioxidant blend: Green tea, Citrus bioflavinoids, Bilberry - 130mg. I started with two at night, but have found that if I take them regularly, just one before bed does the trick.

Grape Skin Extract 20% Proanthocyanidins