Grape Seed extract is one of the most profound and well researched anti-inflammatory compounds and…

What is Grape Seed Extract?

Grape seed extract is a derivative of grape seeds (usually wine grapes) and is mostly made up of proanthocyanidins/procyanidins [R], vitamin E, flavonoids, and polyphenols [R].

Proanthocyanidin is one of the compounds that make up Green Tea extract, and the benefits of green tea may be somewhat replicated by grape seed extract alone.  Proanthocyanidins come from many different fruits, nuts, and plants and have a wide range of effects on the body [R].

My Experience With Grape Seed Extract

I like grape seed extract, but it does initially have an immune stimulating effect, which isn’t great for my overactive Th1 dominant immune system, but it’s good for Th2 dominant people.

So I don’t take this daily, but I think taking a supplement with proanthocyanidins is important, especially for the average person.

Health Benefits of Grape Seed Extract

1) Grape Seed Extract Reduces Blood pressure and Promotes Blood Flow

In a study on humans with an above average vascular risk, grape seed extract was able to improve flow-mediated dilation by 1.1% compared to control [R].

Consumption of the juice containing grape seed extract was found to reduce blood pressure in individuals with risk of high blood pressure [R].

Grape seed extract was found to lower blood pressure in individuals with metabolic syndrome [R].

There may be evidence that grape seed extract reduces factors that lead to heart disease (other than blood pressure) [R], such as reduction of oxidized LDL, helping with prevention of arteriosclerosis [R], as well as antioxidants that protect the blood vessels from damage [R].

2) Grape Seed Extract Possesses Nootropic and Anti-Stress Activity

In a rat model of forced swim test, grape seed extract prevented the decline in levels of a marker for adrenaline (vanillylmandelic acid) and ascorbic acid in urine (both of which decline in relation to stress). It did not affect the levels of these markers in healthy rats [R].

In an animal model of avoidance from a negative stimulus, rats fed the extract learned to avoid the negative stimulus much faster [R].

Grape seed extract was able to increase performance in a test which is indicative of improved spatial memory in aged rats [R].

3) Grape Seed Extract Protects Cognitive Function

Grape seed extract appears to reduce aggregation of brain amyloid cells, improving cognition, and reducing the risk of Alzheimer’s in rats [R].

In a study done on female rats, GSE was able to lower unwanted compounds (hydrogen peroxide, cellular damage, and blood glucose) and increase good compounds (sulfhydryl content) in the hippocampus.

General cognitive ability was also improved, suggesting that grape seed extract can help with the cognitive loss caused by aging [R].

During high Nitric Oxide (NO) production grape seed extract protected the astroglial cells (maintained Glutathione reserves and protected against H2O2 mediated damage) [R].

4) Grape Seed Extract May Protect Stomach and Ameliorate IBS

In a rat model of IBS, grape seed extract was shown to significantly reduce many of the negative symptoms of IBS. The extract was able to increase intestinal integrity (increasing goblet cell density, decreasing claudin 2, Tnf-a, IL1B, IL-6) [R].

Grape seed extract restored the gut flora in IBS rats.  It increased the bacteroid count in both healthy and diseased rats and restored the lactobacilli count [R].

It may prevent stomach ulcers at low doses (about 250 mg) [R]. GSE inhibited cancer cell growth in the stomach in one study [R].

Grape seed extract has been shown to increase intestinal tight junction proteins in healthy rats. GSE was also shown to decrease fecal levels of a marker of intestinal inflammation (calprotectin) [R].

5) Grape Seed Extract Lowers Inflammation

In LPS stimulated macrophages, grape seed extract potently inhibited the inflammatory response (inhibited nitric oxide production, inhibited NFkB translocation, inhibited PGE2, and inhibited iNOS) [R].

In rats fed a high-fat diet, grape seed extract lowered blood levels of CRP and decreased inflammatory markers in white fat tissue (TNF-a, IL-6) [R].

In human macrophages stimulated by LPS, grape seed extract inhibited the secretion of inflammatory markers (MMP 1, 3, 7, 8, 9, 13, NF-kB, p65, AP-1) [R].

In LPS stimulated macrophages, grape seed extract strongly decreased several inflammatory markers (nitric oxide, ROS, iNOS) [R].

In astrocytes, grape seed extract was able to increase the levels of a (sometimes) beneficial cytokine (IL-6). When neuronal cells were challenged with H2O2 the IL-6 elicited anti-inflammatory action [R].

In rats given high doses of LPS, grape seed extract was able to lower the inflammatory response by decreasing several inflammatory compounds (NOx, IL-6, iNOS, and decreased the GSSG/total glutathione ratio) [R].

6) Grape Seed Extract May Improve Osteo and Rheumatoid Arthritis Symptoms

In a rat model of rheumatoid arthritis, Grape Seed Extract decreased many bad changes (synovial inflammation, cartilage and bone erosion, osteoclast activity, Tnf-a, IL-17, 8-isoprostane, type 2 collagen IGG2A) [R].

In a mouse model of autoimmune arthritis, GSE reduced several inflammatory cytokines (IL-21, IL-22, IL-26, Il17), and induced the beneficial Foxp3 (type 2 collagen reactive Treg cells) [R].

Grape seed extract decreases the number of markers for bone erosion (TRAP-positive cells and osteoclast activity) and increased the amount of mature bone-forming components (osteoblasts) [R].

In a rat model of rheumatoid arthritis, grape seed extract was able to significantly reduce many of the inflammatory markers (T-cell subsets, GITR-expressing cells, Th1 cytokines, MCP-1, MIP-2, ICAM-1), and induced the production of Th2 cytokines and Tregs [R].

Grape seed extract was able to reduce several pain indexes in the model of rat osteoarthritis and was able to decrease many of the inflammatory markers (MMP-13, IL-1B, nitrotyrosine, the formation of osteophytes, subchondral bone fractures) [R].

7) Grape Seed Extract Can Ameliorate Asthma, Lung Inflammation and Possesses Anti-Allergenic activity

In a rat model of asthma, grape seed extract was able to significantly reduce airway hyper-responsiveness, decrease inflammation in the bronchoalveolar lavage fluid and the lungs, and decrease several cytokines (IL-4, IL-5, IL-13, and eotaxin-1) [R].

In mast cells, grape seed extract was able to inhibit IgE mediated release of many inflammatory compounds (histamine and hexosaminidase) [R].

In a mouse model of pleurisy, grape seed extract reduced tissue damage and inflammation markers (ICAM-1, IFN-y, IL-6, IL-17A, IL-1B, TNF-a, GITR, and MCP-1). GSE reversed the decreases in some beneficial markers (TGF-B1IL-10, IL-4, IL-5, and IL-13) [R].

8) Grape Seed Extract May Protect Against Cancer

A study done in cells found that grape seed extract was able to help stop the proliferation of prostate cancer cells and cause the cancer cells to die [R].

A study on head and neck squamous cell carcinoma found that grape seed extract destroyed the damaged DNA and induced cell death in the cancerous cells selectively [R].

Grape seed extract was able to protect against the development of UV-induced skin tumors (skin carcinoma) in a study done on rats [R].

In the rat model of breast cancer, grape seed extract was able to reduce tumor multiplicity by fifty percent. This reduction was dependent on what type of food the extract was administered with [R].

In a mouse model of colorectal cancer, grape seed extract at a dose of 200mg/kg (human dose of 1216mg for a 75kg person) decreased tumor weight by 44% [R].

Grape seed extract potentiates the cancer killing potency of the chemotherapy drug doxorubicin. The doxorubicin lowered immune response was reversed by GSE [R].

In a rat model of an intestinal disorder arising from chemotherapy (mucositis), grape seed extract was able to dose-dependently decrease the histological damage score and restore many of the many of the negative markers closer to normal [R].

9) Grape Seed Extract and Metabolic Syndrome

In rats fed a high-fat diet, grape seed extract was able to decrease blood fat levels and decrease the amount of fat accumulation especially in the white fat tissue [R].

In rats fed a high-fat diet, grape seed extract was able to correct elevated triglycerides (dyslipidemia) most likely through the mechanism of suppressing liver fat production [R].

Grape seed extract was able to inhibit lipase activity in test tubes and thus may be useful for reducing free fatty acids and accumulation of fat in fat tissue [R].

10) Grape Seed Extract is Anti-Bacterial

In-vitro grape seed extract was able to inhibit the activity of many bacteria (Bacillus cereus, Bacillus coagulans, Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa).

The extract showed greater effectiveness against gram-positive than gram-negative bacteria [R].

11) Grape Seed Extract Increases Antioxidant Activity

One study found that 300 mg of grape seed extract taken for five days increased antioxidant activity in the blood [R].

Grape seed extract outperformed vitamin C, vitamin E, and B-carotene in protecting the brain plus the liver against cellular damage and DNA damage caused by 12-O-tetradecanoyl phorbol-13-acetate (TPA) [R].

In line with its anti-oxidant activity, grape seed extract protected the liver in a Tylenol model of rat liver damage by increasing an anti-apoptotic gene (Bcl-Xl) [R].

In rats exposed to x-rays, grape seed extract was able to maintain levels of several beneficial markers (GSH, retinol, B-carotene, and ceruloplasmin). In the rats given the extract levels of inflammatory markers were lower (MDA and nitrite) [R].

12) Grape Seed Extract Protects Male Reproductive Health

In rats given ammonium chloride, grape seed extract inhibited the degenerative changes in the testes [R].

In a rat model of testicular torsion (somewhat common in humans), grape seed extract reversed the rise in several key inflammatory markers (malondialdehyde, eNOS, and apoptosis) [R].

13) Grape Seed Extract Protects Skin

In mice exposed to UVB radiation, grape seed extract inhibited the production of several inflammatory markers (pro-inflammatory leukocytes, myeloperoxidase, COX-2, PGE2, cyclin D1, TNF-a, IL-1B, IL-6, PCNA) in both the skin and skin tumors [R].

14) Grape Seed Extract May Reduce Estrogen and Increase Testosterone Levels

High doses of grape seed extract were shown to reduce and inhibit aromatase transcription and activity [R].

15) Grape Seed Extract Reduces Swelling

One study done on fairly healthy, sedentary Japanese women was shown to reduce leg swelling (caused by prolonged sitting) [R].

Grape seed extract inhibits the production of Nitric Oxide (NO) in macrophages. This reduces swelling [R], such as after surgery or injury.  Women who took grape seed extract orally for six months experienced less pain and swelling (edema) after radiation therapy for breast cancer than those who took the placebo [R].

Grape seed extract is able to reduce swelling caused by antigens [R].

16) Grape Seed Extract May Help Diabetic Symptoms

Male diabetic rats treated with grape seed extract and exercise showed improvement in their fat profile, weight loss, bradycardia, and low blood pressure [R].

Because of its antioxidant abilities, grape seed extract was shown to be able to improve oxidative damage (the balance between free radicals and the body’s ability to combat them) and general antioxidant levels in diabetic rats [R].

Another study done on diabetic rats showed that grape seed extract was able to effectively prevent heart damage and disorder caused by diabetes [R].

Grape seed extract has anti-inflammatory properties, and it is effective in preventing damage to the pancreas caused by inflammation in mice with diabetes [R].

Diabetic rats with diabetes-induced bladder dysfunction were found to have improvement in bladder function. Additionally, there was a decrease in oxidative damage levels, in bladder cell death, an increase in nerve growth on the bladder [R].

Grape seed extract strongly inhibits carbohydrate absorption by inhibiting two key markers – alpha-amylase and alpha-glucosidase [R].

In rats fed a high fructose diet, grape seed extract protected against the insulin and blood glucose spike which usually follows after a glucose loading test.

Rats fed the extract also showed higher levels of liver anti-oxidants (catalasesuperoxide dismutase) [R].

In the hippocampus (memory center) of diabetic rats, GSE decreased the production of inflammatory markers (RAGE and NF-kB) [R].

In diabetic rats, grape seed extract was able to protect nerves from oxidative damage, demyelination, and was able to improve nerve conductance [R].

A study done on rats showed that grape seed extract helped protect the pancreatic cells in situations of high-fat content in blood.  The pancreatic cells produce insulin, which aids in maintaining regular blood glucose levels [R].

There is also evidence to suggest that grape seed extract enhances insulin, increasing its ability to stimulate organs [R].

17) Grape Seed Extract May Reduce Food Intake

Grape seed extract reduces food intake, though not necessarily appetite and the reduction of calories is very little [R].

18) Grape Seed Extract is Cardio-Protective

In cholesterol-fed rabbits, grape seed extract significantly inhibited the formation of hardening of the arteries in the aorta [R].

Grape seed extract, when incubated in test tubes, was able to decrease several markers of thrombosis [R]. It reduced the weight and the length of the thrombus and protected the endothelium [R].

In hamsters fed cholesterol, grape seed extract was able to inhibit the formation of hardening of the arteries by 34% and decrease blood cholesterol by 11%. It did this through some mechanism outside of simple anti-oxidant function [R].

In restriction of blood (ischemia) to rat hearts, grape seed extract was able to reduce free radical formation, heart fibrillation, tachycardia, and improve aortic flow and heart flow after the surgery [R].

19) Grape Seed Extract Interacts With Cytochrome P450

Grape seed extract inhibits CYP2C9 and CYP3A4 at a very low concentration, this may increase the uptake and potency of some pharmaceuticals and herbs [R].

20) Grape Seed Extract Has Kidney Protective Effects

In a rat model of kidney toxicity, grape seed extract was able to reduce several negative and inflammatory markers (creatinine, urea, uric acid, IL-1B, TNF-a, MCP-1, TG, LDL, and increased the blood HDL, NO, and cGMP) [R].

In a study on cadmium-induced kidney damage, grape seed extract was able to reduce the increases markers of damage (fat peroxidation, kidney apoptosis) [R].

21) Grape Seed Extract Builds Bone Density

A study done on rats showed that a diet with some calcium plus grape seed extract supplements improved bone formation and bone strength [R].

23) Grape Seed Extract May Help With Oral Health

A study done in cells found that grape seed extract was effective in remineralizing teeth, a process that is used to prevent or reverse early tooth decay.

Tooth samples were washed with a solution containing grape seed extract for eight days, and the data showed them to have been more remineralized than the control groups [R].


Symptoms of chloasma (also known as melasma) have been shown to decrease with low doses of grape seed extract [R].

Potential Risks

Grape seed extract was tested on rats to evaluate its toxicity for use in foods and was found not to have any noticeable toxic effects after 90 days [R].


Some studies use a dose of 300mg whereas others use up to 2g [R]. And most doses converted from rat studies fall in the 1g to a 2g range [R].


Grapeseed extract:

  • Decreased fasting blood insulin concentrations, and improvements in insulin sensitivity [R].
  • Stimulates endothelial nitric oxide synthase (eNOS), increases eNOS in endothelial cells in vitro, and induces endothelium-dependent relaxation (EDR) of blood vessels [R].
  • Reduced Ox-LDL concentrations in blood at a dose of 300mg a day [R].
  • Decreased fructosamine, overall cholesterol, and hsCRP levels in the blood [R].
  • Improved post-ischemic left heart function [R].
  • Decreased heart infarct size, heart fibrillation (VF) and tachycardia, a concentration of reactive oxygen species, and malondialdehyde (MDA) formation in heart perfusate [R].
  • Decreased blood creatine kinase (CK) activity and DNA damage, resulting in the reduction of doxorubicin-induced heart toxicity [R].
  • Reduced activation of the endothelial CD36 gene [R].
  • Suspension of atheroma formation [R].
  • Reduced amount of reactive oxygen species (ROS) [R].
  • A component in grape seed extract is able to block protofibril formation, pre-protofibrillar oligomerization, and initial coil to Alpha-helix/Beta-sheet secondary structure transitions [R].
  • Decreased production of NO, PGE2, iNOS mRNA, NFkB translocation [R].
  • Caused breakdown of TGF-b1 latent complex, releasing active TGF-b1 [R].
  • Inhibited activation of mitogen-activated protein kinases (MAPK) and NF-kB transmission pathways [R].
  • Increased production of milk fat globule epidermal growth factor-8 (MFG-E8),  IL-1b and NLRP3 [R].
  • Activated Nrf2 as well as increased levels of heme oxygenase-1 (HO-1) [R].
  • Increased production of Cpt1a, decreased the production of Fasn and Srebf1 [R].

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