Grape Seed Extract - Get the Facts on Herbal Supplements

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  • Grape seed extracts have shown some beneficial antioxidant effects in preliminary clinical trials.<a href="#hdng0">(More...)</a>

  • IH636 grape seed proanthocyanidin extract An oligomeric proanthocyanidin extracted from grape seeds. IH636 grape seed proanthocyanidin extract exhibits dose-dependent free-radical scavenging and antioxidant properties.<a href="#hdng1">(More...)</a>

  • Laboratory studies have shown that grape seed contains antioxidants-substances that prevent cell damage caused by free radicals, which are highly reactive molecules that can damage cell function.<a href="#hdng2">(More...)</a>



<a name="hdng0"></a>Grape seed extracts have shown some beneficial antioxidant effects in preliminary clinical trials. <a href="http://nccam.nih.gov/health/grapeseed/" TARGET="_blank" [1]</a> NCCAM is studying whether the action of grape seed extract and its components may benefit the heart or have protective effects in the brain.<a href="http://nccam.nih.gov/health/grapeseed/" TARGET="_blank" [1]</a> Grape seed extract is used for conditions related to the heart and blood vessels, such as atherosclerosis (hardening of the arteries), high blood pressure, high cholesterol, and poor circulation. Other reasons for the use of grape seed extract include complications related to diabetes, such as nerve and eye damage; vision problems, such as macular degeneration (which can cause blindness); and swelling after an injury or surgery.<a href="http://nccam.nih.gov/health/grapeseed/" TARGET="_blank" [1]</a> Grape seed extract is generally well tolerated when taken by mouth. It has been used safely for up to 8 weeks in clinical trials.<a href="http://nccam.nih.gov/health/grapeseed/" TARGET="_blank" [1]</a> Grape seed extract is prepared from the seed of grapes. It is available in capsule and tablet forms.<a href="http://nccam.nih.gov/health/grapeseed/" TARGET="_blank" [1]</a> NCI is also funding studies evaluating whether grape seed extract is effective in preventing breast and prostate cancers.<a href="http://nccam.nih.gov/health/grapeseed/" TARGET="_blank" [1]</a> A study funded by the National Cancer Institute (NCI) found that grape seed extract did not reduce the hardening of breast tissue that can occur after radiation therapy for breast cancer.<a href="http://nccam.nih.gov/health/grapeseed/" TARGET="_blank" [1]</a> The interactions between grape seed extract and medicines or other supplements have not been carefully studied.<a href="http://nccam.nih.gov/health/grapeseed/" TARGET="_blank" [1]</a>

Grape seed extracts (GSEs) contain a high concentration of many of the polyphenols in grape skins, in particular, the proanthocyanidins, which are also found in red wine.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1082891" TARGET="_blank" [2]</a> Grape seed extract (GSE) has in vitro antioxidant activity but whether or not it works in vivo is not clear.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1082891" TARGET="_blank" [2]</a> As part of GRN No. 000125, Polyphenolics' GRAS panel was provided with additional chemistry and safety data from newly published studies conducted with commercial grape seed extracts. In an addendum to the GRAS panel report provided in GRN No. 000125, Polyphenolics' GRAS panel acknowledged review of this additional data and information and affirmed its original conclusion that GSE and GPE are GRAS under the conditions of their intended use.<a href="http://www.cfsan.fda.gov/~rdb/opa-g125.html" TARGET="_blank" [3]</a> Acute and subchronic oral toxicity studies conducted in animals fed GSE and GPE, other grape seed extracts, or substances that are components of GSE and GPE showed no relevant compound-related toxicological effects.<a href="http://www.cfsan.fda.gov/~rdb/opa-g125.html" TARGET="_blank" [3]</a> Genotoxicity studies conducted in vivo and in vitro with GSE and GPE, other grape seed extracts, or substances that are components of GSE and GPE demonstrated no mutagenic effects.<a href="http://www.cfsan.fda.gov/~rdb/opa-g125.html" TARGET="_blank" [3]</a>

FDA also mentioned that the recommendation by the National Toxicology Program (NTP) that another grape seed extract product be subjected to substantial toxicity tests raised questions about consensus within the scientific community about the safety of chronic consumption in food of GSE and GPE.<a href="http://www.cfsan.fda.gov/~rdb/opa-g125.html" TARGET="_blank" [3]</a> The subjects of the notice are grape seed extract (GSE) and grape pomace extract (GPE).<a href="http://www.cfsan.fda.gov/~rdb/opa-g125.html" TARGET="_blank" [3]</a> The original subjects of the Polyphenolics' notice were described as grape seed extract (GSE) and grape skin extract (GSKE).<a href="http://www.cfsan.fda.gov/~rdb/opa-g125.html" TARGET="_blank" [3]</a> Polyphenolics reports that the National Cancer Institute nominated a different grape seed extract for evaluation at the May 2001 meeting of the NTP Interagency Committee for Chemical Evaluation and Coordination.<a href="http://www.cfsan.fda.gov/~rdb/opa-g125.html" TARGET="_blank" [3]</a>

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.<a href="http://nccam.nih.gov/health/grapeseed/" TARGET="_blank" [1]</a> Acute, subchronic and chronic oral toxicity studies conducted in animals fed GSE, other grape seed extracts, or substances that are components of GSE showed no relevant compound-related toxicological effects.<a href="http://www.cfsan.fda.gov/~rdb/opa-g124.html" TARGET="_blank" [4]</a> Genotoxicity studies conducted in vivo or in vitro with commercial grape seed extracts or substances that are components of GSE demonstrated no mutagenic effects.<a href="http://www.cfsan.fda.gov/~rdb/opa-g124.html" TARGET="_blank" [4]</a>

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<a name="hdng1"></a>IH636 grape seed proanthocyanidin extract An oligomeric proanthocyanidin extracted from grape seeds. IH636 grape seed proanthocyanidin extract exhibits dose-dependent free-radical scavenging and antioxidant properties. <a href="http://www.cancer.gov/Templates/drugdictionary.aspx?CdrID=38706" TARGET="_blank" [5]</a> The present study provides scientific support for the antistress (adaptogenic), antioxidant and nootropic activities of V. vinifera seed extract and substantiate the traditional claims for the usage of grape fruits and seeds in stress induced disorders.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a> Jayaprakasha GK, Selvi T, Sakaria KK. Antbacterial and antioxidant activities of grape ( Vitis vinifera ) seed extracts.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a>

Koga T, Moro K, Nakamori K, et al. Increase of antioxidative potential of rat plasma by oral administration of proanthocyanidin-rich extract from grape seeds. J Agric Food Chem. 1999; 47 (5):1892"1897.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1082891" TARGET="_blank" [2]</a> Yamakoshi J, Kataoka S, Koga T, Ariga T. Proanthocyanidin-rich extract from grape seeds attenuates the development of aortic atherosclerosis in cholesterol-fed rabbits.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1082891" TARGET="_blank" [2]</a> Grape seed proanthocyanidin extract (GSPE, 0.1% level) has been shown to reduce atherosclerosis in cholesterol-fed rabbits by 30%–50% probably by inhibiting LDL oxidation as lipid levels were not altered while malondialdehyde levels in the aorta (an index of lipid oxidation) were reduced by 25%.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1082891" TARGET="_blank" [2]</a>

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<a name="hdng2"></a>Laboratory studies have shown that grape seed contains antioxidants-substances that prevent cell damage caused by free radicals, which are highly reactive molecules that can damage cell function. It is still unclear how grape seed might affect human health. <a href="http://nccam.nih.gov/health/grapeseed/" TARGET="_blank" [1]</a> In the indigenous Indian system of medicine (Ayurveda), the aerial parts of V. vinifera have been widely used to treat a variety of common and stress related disorders. The composition and properties of grape seeds have been extensively investigated, and reported to have many favourable effects on human health such as the lowering of low-density lipoprotein, reduction of cardiovascular diseases and cancer.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a> In the present investigation, the seed extract of V. vinifera was evaluated for antistress activity in normal and stress induced rats. The extract was studied for nootropic activity in rats and in-vitro antioxidant potential to correlate its antistress activity.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a> Figure 1 Influence of Vitis vinifera seed extract on the 24 h urinary levels of VMA in normal and stress induced rats.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a> Figure 3 Effect of Vitis vinifera seed extract on the mean percent of conditioned avoidance response after oral administration in rats.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a>

The seed extracts of V. vinifera are reported to have antimicrobial and free radical scavenging properties.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a> The antioxidant activity of the seed extract provide mechanistic basis in relieving stress by way of combating oxidative damage.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a> Further investigations are required to characterize the active constituent(s) responsible for observed activities of the seed extract.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a>

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  • Based on the above studies ascorbic acid excretion in urine was taken as an indirect biochemical index to indicate the influence of stress on catecholamine synthesis in rats and antistress (adaptogenic) activity of the Vitis vinifera extract on prior administration of stress induction.<a href="#hdng3">(More...)</a>



<a name="hdng3"></a>Based on the above studies ascorbic acid excretion in urine was taken as an indirect biochemical index to indicate the influence of stress on catecholamine synthesis in rats and antistress (adaptogenic) activity of the Vitis vinifera extract on prior administration of stress induction. <a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a> For the evaluation of antistress activity, groups of rats (n 6) were subjected to forced swim stress one hour after daily treatment of V. vinifera extract.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a>

After attaining complete training of a particular group, the animals were treated with a single dose of scopolamine butyl bromide (1 mg/kg body weight, i.p.), thirty minutes before the next day dosing. The training schedule was continued further with the daily doses of the extract and vehicle until they returned to normal level from scopolamine induced amnesia. The antioxidant activity of V. vinifera was determined based on its ability to scavenge the hydroxyl radicals.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a> Animals receiving 300 mg/kg body weight of the extract have taken seven days whereas, groups treated with 200 and 100 mg/ kg doses of the extract required eight and nine days respectively to reach the point of acquisition (Fig. 3 ).<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a> The acquisition (time to achieve 95% CAR ) for the extract treated groups was quicker and found to be dose dependent.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a> The percent avoidance was always higher in the extract treated groups compared to vehicle treated control group.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a> The final phase of the experiment consisted of administration of V. vinifera extract to the same groups of animals after a recovery period of one week.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a> The third phase of the experiment consists of administration of V. vinifera extract to the same groups of animals after having recovered completely to normal condition.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a>

The antistress and antioxidant activities were correlated with the nootropic activity of the extract since the role of stress and free radicals have been implicated in the loss of memory, concentration and also in Alzheimer's disease.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a> The antioxidant potential of the extract was evaluated in-vitro to support the antistress activity.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a> The plant extract was further evaluated for nootropic activity using conditioned avoidance response in rats.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a> The nootropic activity of the extract as determined from acquisition, retention and retrieval in rats was studied by conditioned avoidance response using Cook's pole climbing apparatus.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a> The CAR of rats administered with the extract of Vitis vinifera or vehicle increased gradually to 95% over seven to ten days.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a> Singh HK, Dhawan BN. Effect of Bacopa monniera (Brahmi) extract on avoidance responses in rats.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a> The quantity of the extract needed for 50% inhibition was found to be 610 μg (Fig. 4 ). Similar effect was produced by ascorbic acid at a concentration of 4875 μg. (Fig. 5 ).<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a> The 24 h urine samples were collected and analyzed for VMA and ascorbic acid for seven consecutive days to study the influence of the extract on the stress induced biochemical changes.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a> The extract also produced significant inhibition of hydroxyl radicals in comparison to ascorbic acid in a dose dependent manner.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a> The extract at quantities of 100, 200, 400 and 800 μg levels scavenged the hydroxyl radicals in a dose dependent manner.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a>

Hydroxyl radical scavenging activity was measured by studying the competition between deoxyribose and the extract for hydroxyl radicals generated from the Fe 3+ -ascorbate-EDTA-H 2 O 2 system.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a> The reaction mixture containing deoxyribose (2.8 mM), ferric chloride (0.1 mM), EDTA (0.1 mM), H 2 O 2 (1 mM), ascorbate (0.1 mM) phosphate buffer (20 mM, pH 7.4) and various quantities of the extracts in a final volume of 1 mL was incubated for 1 h at 37°C. Deoxyribose degradation was measured as TBARS by the method of Ohkawa et al., 1979 and the percentage free radical inhibition was calculated from control.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a>

The aerial parts of Vitis vinifera (common grape or European grape) have been widely used in Ayurveda to treat a variety of common and stress related disorders.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a> Vitis vinifera (Linn.) (Family: Vitaceae) also called as common grape or wine grape or European grape is one of the fruit crops most widely grown throughout the world.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a>

Teissedre PL, Frankel EN, Waterhouse AL, Pele GH, German JB. Inhibition of in-vitro human LDL oxidation by phenolic antioxidants from grapes and wines.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a>

The riped fruits of Vitis vinifera were collected from the Chittor district of Andhra Pradesh, India in the month of October and the seeds were separated from the pulp and shade dried.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a> The dried powdered seed material of Vitis vinifera (5 kg) was extracted with boiling water (25 L) for 45 minutes and the filtrate was evaporated under vacuum below 70°C in a vacuum drier to give a final yield of 50 gm.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank" [6]</a>

The seeds are separated from the skins (for GSE), and the seeds or the pomace of seeds and skin (for GPE) are boiled in water to extract the polyphenolic constituents.<a href="http://www.cfsan.fda.gov/~rdb/opa-g125.html" TARGET="_blank" [3]</a> Polphenolics notes that another grape-derived extract (i.e., grape skin extract (enocianina)) is regulated for use under 21 CFR 73.170 as a color additive in still and carbonated drinks and ades, beverage bases, and alcoholic beverages. Polyphenolics uses the United States Department of Agriculture (USDA) 1994-1996 Continuing Surveys of Food Intakes by Individuals and the 1998 Supplemental Children's Survey to estimate the intake of GSE and GPE from their intended use.<a href="http://www.cfsan.fda.gov/~rdb/opa-g125.html" TARGET="_blank" [3]</a> Because a different preparation of grape skin extract (enocianina) is currently regulated for use under 21 CFR 73.170 as a color additive in beverages, the Office of Food Additive Safety (OFAS) consulted with the Office of Nutritional Products, Labeling, and Dietary Supplements (ONPLDS) and Polyphenolics regarding the common or usual name of the notified substance, grape skin extract (GSKE).<a href="http://www.cfsan.fda.gov/~rdb/opa-g125.html" TARGET="_blank" [3]</a> In a letter, dated April 30, 2003, Polyphenolics requested to change the common or usual name of the notified substance from grape skin extract (GSKE) to grape pomace extract (GPE). Section 403(i)(2) of the FFDCA provides that a food shall be deemed to be misbranded unless its label bears the common or usual name of each ingredient.<a href="http://www.cfsan.fda.gov/~rdb/opa-g125.html" TARGET="_blank" [3]</a>

Polyphenolics describes the method of manufacture of GSE and GPE. The extracts are manufactured from fresh grapes, which are inspected for quality and screened for defects.<a href="http://www.cfsan.fda.gov/~rdb/opa-g125.html" TARGET="_blank" [3]</a> The extract is then filtered with diatomaceous earth and passed through a column of trimethylolpropane trimethacrylate (TMPTMA). Polyphenolics notes that grape phenolic constituents preferentially adsorb to the TMPTMA resin, while other grape constituents such as minerals and organic acids pass through the column and are discarded.<a href="http://www.cfsan.fda.gov/~rdb/opa-g125.html" TARGET="_blank" [3]</a>

Polyphenolics states that the heavy metals composition of GSE and GPE are within FDA tolerances for grapes.<a href="http://www.cfsan.fda.gov/~rdb/opa-g125.html" TARGET="_blank" [3]</a>

The grapes are de-stemmed, crushed, and pressed, leaving a pomace residue of seeds and skin.<a href="http://www.cfsan.fda.gov/~rdb/opa-g125.html" TARGET="_blank" [3]</a> The seeds are then removed, and the extract is cooled, enzymatically depectinized, and the pH is adjusted.<a href="http://www.cfsan.fda.gov/~rdb/opa-g125.html" TARGET="_blank" [3]</a>

CSIRO data (unpublished) indicates that GSEs inhibit low-density lipoprotein (LDL) oxidation and reduce aortic ring constriction in vitro. Extract of oligomeric proanthocyanidins from other sources such as Pycnogenol from pine bark enhances nitric oxide (NO) production from vascular endothelium in vitro.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1082891" TARGET="_blank" [2]</a> Although red wine extract inhibits endothelin (ET-1) production, neither isolated red wine polyphenols (quercetin, resveratrol, D-,L-catechin, D-,L-epicatechin) nor the anthocyanins delphinidin, pelargonidin, cyanidin, peonidin, petunidin, or malvidin affect ET-1 production. Although there is no data yet relating impaired FMD to cardiac events in subjects without coronary disease, those patients with coronary disease who have very impaired FMD have more events.<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1082891" TARGET="_blank" [2]</a>
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1. <a href="http://nccam.nih.gov/health/grapeseed/" TARGET="_blank">Grape Seed Extract [NCCAM Herbs at a Glance]</a>
<a href="http://nccam.nih.gov/health/grapeseed/" TARGET="_blank">http://nccam.nih.gov/health/grapeseed/</a>

2. <a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1082891" TARGET="_blank">Effect of Grape Seed Extract and Quercetin on Cardiovascular and Endothelial Parameters in High-Risk Subjects</a>
<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1082891" TARGET="_blank">http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1082891</a>

3. <a href="http://www.cfsan.fda.gov/~rdb/opa-g125.html" TARGET="_blank">FDA/CFSAN: Agency Response Letter: GRAS Notice No. GRN 000125</a>
<a href="http://www.cfsan.fda.gov/~rdb/opa-g125.html" TARGET="_blank">http://www.cfsan.fda.gov/~rdb/opa-g125.html</a>

4. <a href="http://www.cfsan.fda.gov/~rdb/opa-g124.html" TARGET="_blank">FDA/CFSAN: Agency Response Letter: GRAS Notice No. GRN 000124</a>
<a href="http://www.cfsan.fda.gov/~rdb/opa-g124.html" TARGET="_blank">http://www.cfsan.fda.gov/~rdb/opa-g124.html</a>

5. <a href="http://www.cancer.gov/Templates/drugdictionary.aspx?CdrID=38706" TARGET="_blank">Definition of IH636 grape seed proanthocyanidin extract - National Cancer Institute Drug Dictionary</a>
<a href="http://www.cancer.gov/Templates/drugdictionary.aspx?CdrID=38706" TARGET="_blank">http://www.cancer.gov/Templates/drugdictionary.aspx?CdrID=38706</a>

6. <a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank">Adaptogenic and nootropic activities of aqueous extract of Vitis vinifera (grape seed): an experimental study in rat model</a>
<a href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917" TARGET="_blank">http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=547917</a>

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