GRAPE SEED
BENEFITS AND SIDE EFFECTS
April 10, 2007
RELATED TERMS
Grape Seed, Grape Seed Extract, Muskat [Vitis vinifera L and V. coignetia.
Family:Vitaceae]

ABOUT GRAPE SEED EXTRACT...
Grape seed is rich in flavonoids, phytochemicals that have antioxidant properties.
Antioxidants are believed to prevent and control numerous ailments by
safeguarding cells against the ravages of unstable oxygen molecules, i.e. the free
radicals. Grape seed's anti-oxidative activities are 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 and its extract may benefit people
with heart disease and cancer.

ARE THERE ANY SCIENTIFIC EVIDENCE ON THE HEALTH BENEFITS OF GRAPE
SEEDS OR GRAPE SEED EXTRACTS?

Grape seed extracts promote bone formation.
A high-calcium diet combined with grape seed proanthocyanidins extract
supplement is more effective in reversing mandibular condyle bone debility in rats.
[2]

Grape seed extracts have anti-stress and anti-oxdation activities.
In a study of rats, grape seed extract showed antistress (adaptogenic),
antioxidant and nootropic activities. [3] Activin, a grape seed-derived
proanthocyanidin extract, was shown to reduce the inflammatory response and
the oxidative stress developed in systemic sclerosis patients [16]

Grape seed extracts have anti-cancer activities and protect chromosome.
Researchers at University of Alabama at Birmingham found that grape seed
extract was chemo-preventive from their studies using animal model of breast
cancer. However, diet had a strong impact to the grape seed extract's
chemopreventive activity. [4]

Japanese researchers  found that grape seed extract could prevented
H(2)O(2)-induced chromosomal damage in a dose proportional fashion. [5] Llopiz
N from Spain showed 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]

Researchers at University of Colorado Health Sciences Center (UC), Denver, found
a strong synergistic effect of grape seed extract and doxorubicin for breast cancer
treatment, independent of estrogen receptor status of the cancer cell. [9]

They also found the anti-angiogenic potential of grape seed extract possesses an
anti-angiogenic potential was associated with its antiproliferative, proapoptotic
and inhibition of MMP-2 secretion in endothelial cells. [11]

Grape seed extract was shown to against prostate cancer.
Same group from UC also found that grape seed extract possessed 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] They also found that grape seed extract could induce
apoptotic death of human prostate carcinoma DU145 cells via mitochondrial
damage and cytochrome c release in cytosol resulting in PARP cleavage. [17]

Grape seed extract was shown to against breast cancer.
Eng ET et al at Beckman Research Institute of the City of Hope, CA, found that
procyanidin B dimers in red wine and grape seed could be used as
chemopreventive agents against breast cancer by suppressing in situ estrogen
biosynthesis. [13]

Grape seed extract may help prevent thrombus formation and atherosclerosis.
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, found commercial grape extracts
prevented the development of aortic atherosclerosis by 68% (EGS), 63% (EGT),
and 34% (GSE). [7]

Grape seed extracts were shown to have anti-hyperglycemic effects on diabetes.
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]

Grape seed extracts may be used in weight management or obesity treatments
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]

Grape seed extracts may promote wound healing.
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 seed extracts may prevent cataract formation.
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]

Grape seed extracts have been claimed to lower cholesterol.
But, the evidence is insufficient.  Vigna GB et al, found that their polyphenolic
extract of grapes (Leucoselect-Phytosome [LP]) 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]

ARE THERE ANY STUDIES ON THE SIDE EFFECTS OR TOXICITY OF GRAPE
SEED?
Grape seeds appear to be safe and they are one of the popular supplements in
the market. There are several studies citing its side effects listed as follows:

Researchers at Huntingdon Life Sciences investigated  the safety of grape seed
extract by feeding rats with grape seed extracts (two products) for three
months.They monitored their body weight and feed consumption throughout the
study. At the end of the study, they conducted a full necropsy, blood testings and
histologic examination and they concluded that a dietary concentration of 2.5%
grape seed extract has no observed adverse effect level (NOAEL). [20]

Japanese researchers evaluated the toxicity of grape seed extract using 344 rats
and concluded that no evidence of acute oral toxicity (side effect) at dosages of 2
and 4 g/kg. [21]

The Wren Group, Nevada, found that high-dose grape seed extract might reduce
serum iron levels in male rats. Otherwise, administratin of grape seed extract for
90 days did not induce any significant toxicological effects in their study of rats.
[22]

Ray S. et al at Long Island University also concluded that grape seed extract was
safe and did not cause any detrimental (side) effects in their study of rats. [23]

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                               REFERENCES

[1] Ariga T The antioxidative function, preventive action on disease and utilization of
proanthocyanidins. Biofactors. 2004;21(1-4):197-201.[2] Ishikawa M et al, Grape seed
proanthocyanidins extract promotes bone formation in rat's mandibular condyle. Eur J Oral
Sci. 2005 Feb;113(1):47-52.[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.
Grape seed extract is a rich source of antioxidants. Various studies have shown that it may have benefits on bone formation, wound
healing, high cholesterol, atheroslerosis  and cataract. Some studies have also demonstrated its anti-stress, anti-oxidative, DNA
protection and anti-cancer activties.