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

INTRODUCTION
As discussed previously, grape seed has lots of flavonoids, and these flavonoids have antioxidant properties. It is
known that most anti-oxidants protect cells against the ravages of unstable oxygen molecules. From research
findings, we know that the antioxidant activities of grape seed extracts are even stronger than vitamins C and E and
the antioxidant activities of grape seed extracts may involve radical scavenging, quenching, and enzyme-inhibiting
actions. [1]

The most important flavonoids of grape seed extracts are proanthocyanidins. Proanthocyanidins are procyanidolic
oligomers, and poroantocyanidins may benefit people at risk of various conditions such as stress, atherosclerosis,
wound healing, cancer, bone formation, cataracts and diabetes. [1,2, 4,5, 7-11, 13, 16-19] Grape seed extracts may
also benefit people with high cholesterol or on weight management. [14, 15] For details, please, read: Grape seed
extract benefits.
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GRAPE SEED EXTRACT SIDE EFFECTS
In general, most herbal supplements side effects include nausea, itching, dizziness, stomach upset, diarrhea,
headache, sore throat, cough, and rash. Grape seed extract may act as a blood thinner, thus, one may expect
bleeding is the one of grape seed extract side effects. Oppositely, grape seed extracts appear to be safe and they
are one of the popular supplements in the market. Grape seed extracts side effects, or adverse, toxic effects have
been monitored in several research reports. Here is a summary of these articles:

1. 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]

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

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

4. 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]

Though grape seed extracts appear to be safe in the studies, the compositions of the dosage forms in these studies
and those available in the market may not be the same. Thus, users should discuss with their medical doctors before
taking the supplements. Further, users also need to monitor their body conditions, to observe if there is any possible
side effects.

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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.
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