Grape seed benefits, grape seed extract benefits
Grape Seed Extract Muskat [Vitis vinifera L and V. coignetia. Family:Vitaceae]

Grape seed extract is rich in flavonoids, these phytochemicals have antioxidant properties. Antioxidants are believed to
be able to prevent and control numerous ailments by safeguarding cells against the ravages of unstable oxygen
molecules, i.e. the free radicals. The antioxidative activities of grape seed extracts are found to be much stronger than
vitamin C and vitamin E and may involve radical scavenging, quenching, and enzyme-inhibiting actions. [1]

The most valuable flavonoids in grape seed extract are procyanidolic oligomers (also known as proanthocyanidins).
Beyond their antioxidant powers, proanthocyanidins may also help atherosclerosis, gastric ulcer, large bowel cancer,
cataracts and diabetes. [1] Thus, grape seed extracts are believed to benefit people with heart disease and cancer.

Though grape seed extract has been promoted as a health supplement for cancer and heart disease, grape seed
extract showed antistress (adaptogenic), antioxidant and nootropic activities in a study. [3] Grape seed-derived
proanthocyanidin extract is also able to reduce the inflammatory response and the oxidative stress developed in
systemic sclerosis patients [16] Thus, grape seed extract may have many other health benefits.
Hence, this section
overviews the potential health benefits of grape seed extract based on research findings.

A few years ago, it has been shown that intraperitoneal injection of grape seed proanthocyanidin extract attenuated
collagen-induced arthritis in mice. [25] Thus, some researchers believe that g
rape seed extract may benefit people at
risk of certain bone conditions. In a study, g
rape-seed proanthocyanidin extract administration ameliorated the arthritic
symptoms of collagen-induced arthritis, which are representative of cartilage and bone destruction. Grape-seed
proanthocyanidin extract treatment reduced the formation of tartrate-resistant acid phosphatase-positive multinucleated
cells and osteoclast activity and increased differentiation of mature osteoblasts. Osteoblasts are cells from which bone
develops, while osteoclast are large multinucleate cells found in growing bone that resorbs bony tissue, as in the
formation of canals and cavities. Grape-seed proanthocyanidin extract improved the arthritic manifestations of collagen-
induced arthritis mice by simultaneously suppressing osteoclast differentiation and promoting osteoblast differentiation.
[2] The results of this particular study suggest that grape-seed proanthocyanidin extract may benefit people at risk of
inflammation-associated bone destruction. In another study, grape seed proanthocyanidin extract (100 mg/kg or 300
mg/kg) or saline was given orally three times per week for 4 weeks after the monosodium iodoacetate injection.
Monosodium iodoacetate injection induced arthritis (MIA) at the knee of rats. Administration of grape seed
proanthocyanidin extract to the MIA-treated rats significantly increased the symptoms and this resulted in recovery of
hind paw weight distribution. Grape seed proanthocyanidin extract also reduced the loss of chondrocytes (cells found in
cartilage) and proteoglycan ( glycoproteins, a major component of the animal extracellular matrix), and it reduced the
number of subchondral bone fractures in the MIA-treated rats. Subchondral bone provides support for the cartilage of
the articular surface. These results also indicate the potential health benefits of grape seed proanthocyanidin extract on
people at risk of arthritis. [24]

As mentioned before, grape seed extract has been promoted as a supplement for people at risk of cancer. On the other
hand, it is known that grape seed extract could prevent H(2)O(2)-induced chromosomal damage in a dose proportional
fashion. [5]  Grape seed extract possesses an anti-angiogenic potential, which is associated with its antiproliferative,
proapoptotic and inhibition of MMP-2 secretion in endothelial cells. [11] It is clear that grape seed extract may have DNA
protection function. Thus, this section discusses the evidence for grape seed extract's potential health benefits in this

Bladder Cancer - A significant inhibitory effect of  grape seed extract on two different bladder cancer cell lines T24 and
HTB9 viability was observed, which was due to apoptotic cell death. [27]

Breast Cancer - Researchers at University of Alabama at Birmingham stated that grape seed extract was chemo-
preventive based on their studies using animal model of breast cancer. [4] While researchers at Beckman Research
Institute of the City of Hope, CA, found that procyanidin B dimers in red wine and grape seed suppress in situ estrogen
biosynthesis. [13] Studies have shown that a woman’s risk of developing breast cancer is related to her exposure to
hormones that are produced by her ovaries (endogenous estrogen and progesterone). [
X] While the researchers at
University of Colorado Health Sciences Center, Denver, found a strong synergistic effect of grape seed extract and
doxorubicin on breast cancer treatment. [9] Thus, grape seed extracts may potentially benefit people at risk of

Oral squamous cell carcinoma - A recent study has shown the apoptotic potential of grape seed extract, confirmed by
significant inhibition of cell growth and viability in a dose- and time- dependent manner without inducing damage to non-
cancerous cell line human umbilical vein endothelial cells. [25]

Liver Cancer -  It was also found that procyanidins of grape seed extract  were more effective than the corresponding
individual monomers, catechin and epicatechin, to prevent DNA lesions in hepatocytes (liver cells). [10]

Prostate cancer. - Grape seed extract possesses in vivo anticancer efficacy against hormone-refractory human prostate
cancer, which was associated with grape seed extract 's antiproliferative, proapoptotic and antiangiogenic activities
together with up regulation of insulin-like growth factor binding protein. [12] In a study, grape seed extract induced
apoptotic death of human prostate carcinoma DU145 cells via mitochondrial damage and cytochrome c release in
cytosol resulting in PARP cleavage. [17]

Japanese researchers found that grape seed extract procyanidins and their antioxidative metabolites (especially the
higher molecular weight procyanidins in the grape seed extract) prevented the progression of cataract formation by their
antioxidative action. [19] Thus, grape seed extract may benefit people at risk of cataract.

Grape seed extracts benefits - diabetes, obesity and high cholesterol profiles?
Grape seed extract- procyanidins was found to have antihyperglycemic effect in a study of diabetic rat. And, the way that
procyanidin (grape seed extract ) affects the activities of insulin-sensitive cell lines was very similar to insulin's. [8]

In a study, grape seed extract rich in bioactive phytochemicals showed inhibitory activity on the fat-metabolizing enzymes
pancreatic lipase and lipoprotein lipase, suggesting that grape seed extract might be useful as a treatment to limit
dietary fat absorption and the accumulation of fat in adipose tissue. [15]

But, the evidence is insufficient.  Vigna GB et al, found that their polyphenolic extract of grapes had no obvious
modification of total cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C) and LDL-C in their
study of heavy smokers. [14]

inflammatory bowel disease
Grape seed extract (1% of dry feed weight) ameliorated inflammatory bowel disease indices, increased colonic goblet
cell numbers and decreased myeloperoxidase levels in the large intestine of  IL10-deficient mice (IL10KO).
Myeloperoixdase is a peroxidase enzyme occurring in phagocytic cells that can oxidize halide ions, producing a
bactericidal effect.  Concomitantly, grape seed extract supplementation attenuated inflammation, decreased the
expression of pore forming tight junction protein claudin, a membrane protein, juxtaposed strands of which form tight
junctions between epithelial cells, and further grape seed extract increased levels of Lactobacilli and Bacteroides in the
gut microbiota of IL10KO mice. [26]

Vascular Conditions
Atherosclerosis is the build up of a waxy plaque on the inside of blood vessels, and thrombus is a stationary blood clot
along the wall of a blood vessel, frequently causing vascular obstruction. We don't want these things in our body.
Researchers from Japan found that proanthocyanidin (grape seed extract) was able to inhibit thrombus formation in the
carotid artery. The anti-thrombotic effect of proanthocyanidin may be due to a direct inhibitory effect on platelets. [6]
While, scientists at Universite Montpellier II, France, showed commercial grape extracts prevented the development of
aortic atherosclerosis. [7] Thus, grape seed extract may benefit people at risk of these conditions.

Khanna S and his group at The Ohio State University Medical Center, Columbus, demonstrated that grape seed
proanthycyanidin extract alone was able to drive vascular endothelial growth factor. Topical application of grape seed
proanthycyanidin extract accelerated wound contraction and closure. Grape seed proanthycyanidin extract treatment
was associated with a more well-defined hyperproliferative epithelial region, higher cell density, enhanced deposition of
connective tissue, and improved histological architecture. [18]

Grape seeds appear to be safe, as they are one of the popular supplements in the market. In a few studies, limited
grape seed extract side effects were demonstrated. [20-23] However, high-doses of grape seed extract may reduce
serum iron levels. [22]

Grape seed extract - bad cholesterol
Grape seed side effects
Grape Seed Oil Benefits and Side Effects
[1] Ariga T The antioxidative function, preventive action on disease and utilization of proanthocyanidins. Biofactors. 2004;21(1-4):197-201.[2]
Park JS et al, Grape-seed proanthocyanidin extract as suppressors of bone destruction in inflammatory autoimmune arthritis. PLoS One.
2012;7(12):e51377. doi: 10.1371

[3] Sreemantula S et al, Adaptogenic and nootropic activities of aqueous extract of Vitis vinifera (grape seed): an experimental study in rat
model., BMC Complement Altern Med. 2005 Jan 19;5(1):1[4] Kim H et al, Chemoprevention by grape seed extract and genistein in
carcinogen-induced mammary cancer in rats is diet dependent. J Nutr. 2004 Dec;134(12 Suppl):3445S-3452S.[5] Sugisawa A et al, Grape
seed extract prevents H(2)O(2)-induced chromosomal damage in human lymphoblastoid cells. Biol Pharm Bull. 2004 Sep;27(9):1459-61.
[6] Sano T et al, Anti-thrombotic effect of proanthocyanidin, a purified ingredient of grape seed Thromb Res. 2005;115(1-2):115-21. [7] Auger
C et al, Phenolics from commercialized grape extracts prevent early atherosclerotic lesions in hamsters by mechanisms other than
antioxidant effect. J Agric Food Chem. 2004 Aug 11;52(16):5297-302.[8] Pinent M et al, Grape seed-derived procyanidins have an
antihyperglycemic effect in streptozotocin-induced diabetic rats and insulinomimetic activity in insulin-sensitive cell lines, Endocrinology.
2004 Nov;145(11):4985-90. Epub 2004 Jul 22.[9] Sharma G et al, Synergistic anti-cancer effects of grape seed extract and conventional
cytotoxic agent doxorubicin against human breast carcinoma cells., Breast Cancer Res Treat. 2004 May;85(1):1-12.[10] Llopiz N et al,
Antigenotoxic effect of grape seed procyanidin extract in Fao cells submitted to oxidative stress. J Agric Food Chem. 2004 Mar 10;52(5):
1083-7. [11] Agarwal C et al, Anti-angiogenic efficacy of grape seed extract in endothelial cells, Oncol Rep. 2004 Mar;11(3):681-5.[12] Singh
RP et al, Grape seed extract inhibits advanced human prostate tumor growth and angiogenesis and upregulates insulin-like growth factor
binding protein-3, Int J Cancer. 2004 Feb 20;108(5):733-40.[13] Eng ET et al, Suppression of estrogen biosynthesis by procyanidin dimers
in red wine and grape seeds, Cancer Res. 2003 Dec 1;63(23):8516-22.[14] Vigna GB et al, Effect of a standardized grape seed extract on
low-density lipoprotein susceptibility to oxidation in heavy smokers. Metabolism. 2003 Oct;52(10):1250-7.[15] Moreno DA et al, Inhibitory
effects of grape seed extract on lipases, Nutrition. 2003 Oct;19(10):876-9.[16] Kalin R et al, Activin, a grape seed-derived proanthocyanidin
extract, reduces plasma levels of oxidative stress and adhesion molecules (ICAM-1, VCAM-1 and E-selectin) in systemic sclerosis, Free
Radic Res. 2002 Aug;36(8):819-25.[17] Agarwal C et al, Grape seed extract induces apoptotic death of human prostate carcinoma DU145
cells via caspases activation accompanied by dissipation of mitochondrial membrane potential and cytochrome c release, Carcinogenesis.
2002 Nov;23(11):1869-76.[18] Khanna S et al,  Dermal wound healing properties of redox-active grape seed proanthocyanidins, Free Radic
Biol Med. 2002 Oct 15;33(8):1089-96.[19] Yamakoshi J et al, Procyanidin-rich extract from grape seeds prevents cataract formation in
hereditary cataractous (ICR/f) rats. J Agric Food Chem. 2002 Aug 14;50(17):4983-8. [20] Subchronic 3-month oral toxicity study of grape
seed and grape skin extracts. Food Chem Toxicol. 2002 Dec; 40(12):1731-43.[21] Safety evaluation of proanthocyanidin-rich extract from
grape seeds. Food Chem Toxicol. 2002 May;40(5):599-607.[22] 90 day oral toxicity study of a grape seed extract (IH636) in rats. J. Agric
Food Chem. 2002 Mar. 27;50(7):2180-92.
[23] Acute and long-term safety evaluation of a novel IH636 grape seed proanthocyanidin extract.
Res Commun Mol Pathol Pharmacol. 2001 Mar-Apr;109(3-4):165-67. [24] Woo YJ et al, Grape seed proanthocyanidin extract ameliorates
monosodium iodoacetate-induced osteoarthritis. Exp Mol Med. 2011 Oct 31;43(10):561-70 [25] Cho ML et al, Grape seed proanthocyanidin
extract (GSPE) attenuates collagen-induced arthritis. Immunol Lett. 2009 Jun 4;124(2):102-10. [25] Aghbali A, et al, Induction of apoptosis by
grape seed extract (Vitis vinifera) in oral squamous cell carcinoma. Bosn J Basic Med Sci. 2013 Aug;13(3):186-91. [26] Wang H, et al,
Dietary grape seed extract ameliorates symptoms of inflammatory bowel disease in IL10-deficient mice. Mol Nutr Food Res. 2013 Aug 21.
[27] Raina K, et al, Role of oxidative stress in cytotoxicity of grape seed extract in human bladder cancer cells. Food Chem Toxicol. 2013 Jul
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