Grape Seed Extract’s Powerful Cardio Protection

By: Byron J. Richards, Board Certified Clinical Nutritionist

Red grape seed extracts (GSE) are a powerful cardioprotective compound.  They strengthen your arteries/capillaries, and offer rather dramatic antioxidant protection for your arteries and heart. Also, through a number of mechanisms they reduce the likelihood that plaque will form in your arteries. 

New molecular science shows that the effects of GSE are much more diverse than previously understood.  GSE works actively at the gene transcription level to promote changes favorable to cardiovascular health that include reducing inflammation and improving cholesterol and triglycerides metabolism.  They have even been found to have natural germ regulating properties and are a potent anti-candida compound. 

What Are Grape Seed Extracts?

A great deal of grape research has been spurred on by what is known as the French Paradox, a diet in which people consume higher saturated fats but with far less heart disease.  Red wine has been actively researched, since 1936 by Professor Jacques Masquelierin, in effort to explain why it may be protective. Contemporary research has validated, explained, and expanded on the earlier findings.  For example, in 2006 researchers pinpointed that compounds in red wine relaxed your circulation and that these compounds were highest in red wines from southwestern France and Sardinia, regions that are associated with increased longevity1.  In 2004 researchers found that postmenopausal women who consumed red wine absorbed less fat2 from a meal (compared to those who drank water).  So by all means, have red wine in moderation with your largest meal of the day, as desired. 

Polyphenols are a broad group of substances found in all plants.  Flavonoids are one type of polyphenol, among thousands of different flavonoids.  Red grapes are a rich source of a type of flavonoid called a proanthocyanidin.  Other common foods that contain some proanthocyanidins are apples, cinnamon, cocoa, cranberry, green tea, and black tea.  White grapes contain proanthocyanidins, but many less than red grapes.  All parts of red grapes contain some proanthocyanidins, including the juice, skins and seeds. 

Without any question, the highest source of small molecule and highly bioactive proanthocyanidins are found in red grape seeds.  The research in this report is based on the use of GSE.  Please do not be confused and think this research translates to products made from white grapes or with grape skins, or even red wine.  It is obvious that having any proanthocyanidins in your diet, regardless of their source, is beneficial to your health.  However, when you are looking to use a nutritional product to support your health you want standardization of the highly bioactive compounds that have been proven to assist health.  Even within GSE products there is variation in quality, just as various red wines have more proanthocyanidins than others. 

It is a favorite ploy of misleading marketers of white grape products and lower quality red grape products to quote red grape seed extract research, since the research on their compounds is lacking and inferior.  For the purpose of dietary supplements, only red grape seed extracts have the overwhelming science behind them. 

One more common confusion people have relates to ORAC value (ORAC= Oxygen Radical Absorbance Capacity).  ORAC is a way to measure the antioxidant activity of any substance for one type of free radical (peroxyl free radical).  It is fine if a product has a high ORAC value, but ORAC values are an indirect and imperfect measurement that have not been proven to be associated with any health benefit.  ORAC fails to miss the value of many compounds to quench the wide variety of free radical types and it does not begin to evaluate how a nutrient works in your body.  While red wine has a significantly higher ORAC value than white wine, many compounds can test high in ORAC value and not even hold a candle to what grape seed extracts actually do to assist your health.  I bring this up because higher ORAC values in no way mean a better product.  These ORAC values are being used by various product manufacturers and network marketing companies to mislead the public on the value of a given nutritional compound, implying superiority based on an ORAC score. 

The tested science behind a specific nutritional compound helps you predict how it may be able to help your health.  The science I review in this report is specifically on red grape seed extracts (GSE).

How Grape Seed Extract Protects Your Cardiovascular System

It has long been understood that GSE offers potent vascular protection.  Early on this was attributed to high caliber antioxidant mechanisms that guarded against plaque accumulation in the walls of your arteries.  GSE also attaches itself to collagen and can significantly strengthen collagen if it is weakened.  This aspect of GSE helps the integrity of the structure of your collagen rich vascular system.  In clinical practice it is one of the best nutrients to prevent bruising and breaking capillaries, including spider veins.  The new science explains that GSE works in many ways to support cardiovascular well-being.

One way that GSE assists your cardiovascular system is by helping your arteries relax3 so that blood can flow easier.  Through a mechanism of gene transcription4 GSE helps turn on the important enzyme known as nitric oxide synthase, which produces the friendly nitric oxide (eNOS) that is required for the proper relaxed tone of your circulatory system and the smooth regulation of your blood pressure.

Another kind of nitric oxide (iNOS) is induced from different kinds of stress, such as chemical exposure, which is highly inflammatory in nature and damaging to your cardiovascular system.  GSE has a unique talent.  As mentioned above it helps make friendly nitric oxide (eNOS).  On the other hand, it actually helps regulate the main gene signal involved with inflammation5 (NF-kappaB), in turn reducing inflammation and preventing the release of the inflammatory form of nitric oxide (iNOS).

One type of cardiovascular toxin common to Americans is that produced from poor dental hygiene.  In fact, unfriendly bacteria in your mouth can easily enter your circulation and release toxicity that causes platelets to stick together, significantly increasing your risk for a heart attack or stroke.  GSE has been shown to reduce the oxidative stress associated with such bacterial toxins, directly turning off the unfriendly nitric oxide production (iNOS) they cause.  The researchers concluded6, “Our findings demonstrate that proanthocyanidins have potent antioxidant properties and should be considered a potential agent in the prevention of periodontal diseases.”  Other research also shows GSE helps keep platelets7 from sticking together, along with the fact it helps strengthen gum tissue (GSE helps any collagen structure); it can be seen to assist this issue in multiple ways.

Smokers are famous for having sticky platelets because cigarettes have at least 80 chemical toxins that irritate platelets, which promote inappropriate clotting, increasing the risk for a heart attack or stroke.  A study showed that GSE significantly reduced the platelet stickiness8 in male smokers.

A known method of inducing experimental heart injury is to expose rats to the cardiotoxin isoproterenol.  Researchers found that GSE protected the heart9 from experimentally induced isoproterenol injury. The researchers concluded that grape seed proanthocyanidins have “a significant effect in the protection of the heart.”

Another common cardiovascular irritant faced by millions of Americans is the toxins produced from an overgrowth of candida albicans in the digestive tract and/or sinuses.  While candida can enter the circulation and infect your heart, this only happens in seriously immune compromised patients.  For most people it is the toxins of candida that act as a cardiovascular irritant by entering your circulation, which also makes you feel tired, irritable, and foggy.  A groundbreaking study shows that GSE directly reduced candida overgrowth10 as well as extended the survival of mice subjected to experimental candida overgrowth.

In one study rats were exposed to lead, with one group getting lead and GSE.  While the GSE did not detoxify the lead, it did protect the rats from cardiovascular damage11.  Lead exposed rats with no GSE protection developed significantly high blood pressure and elevated heart rate, whereas GSE protected rats did not develop these cardiovascular problems when exposed to lead.

Chinese researchers proved that GSE directly boosted antioxidant activity in heart cells12, in turn protecting heart cells from free radical induced death.  In their next experiment they tested the chemotherapy drug Adriamycin, which has a limited dose in clinical practice because it is highly toxic to the heart.  They showed that pretreating animals with GSE significantly reduced the heart-related toxicity13, including cell death and DNA fragmentation.  They identified that this was partly due to antioxidant mechanisms but also found GSE was helping regulate genes that helped the heart cells withstand the stress of the toxin.  In addition to helpful protection during chemotherapy, findings of this type suggest that GSE would help those who have to be on toxic drugs regularly – such as those on organ transplant medication or long-term antibiotics.

GSE exerts extraordinary protection to the heart in the face of diabetes.  In diabetes excessive blood sugar links the flexible heart muscle like cement through a process known as glycation (AGEs – advanced glycation end products).  This results in eventual heart failure and heart attacks.  A recent detailed molecular animal study showed that GSE reduced the formation of AGEs in the heart14, maintained the health of mitochondria (cell engines), and preserved the healthy structure of the heart.  GSE was shown to work at the gene transcription level, down-regulating the primary inflammatory gene signal NF-kappaB.  The researchers concluded that GSE “plays an important role against diabetic cardiomyopathy. With the decreasing of AGEs, it can ameliorate glycation associated cardiac damage.  This study may provide a new recognition of natural medicine for the treatment of diabetic cardiomyopathy.”

Other researchers found that GSE directly turns down the gene signaling system that causes AGEs to form, while simultaneously reducing oxidative damage.  This would not only be helpful to the heart but also helpful to your entire circulatory system15 if your blood sugar is running high.  The researchers concluded that GSE “may have therapeutic potential in the prevention and treatment of vascular complications in diabetic patients.”

It can be understood that the fundamental role of GSE in your body is one of added protection against multiple stressors in life.  In addition to all the cardiovascular benefits recent research has also shown that GSE reduces the formation of amyloid plaque in the brain that causes Alzheimer’s disease16 by 30 to 35 percent while maintaining cognitive function at a higher level.  GSE also protects your skin from UV radiation17, by helping as an antioxidant and also helping at the gene transcription level by modulating NF-kappaB.

Grape Seed Extract Helps Fat and Cholesterol Metabolism

In animal studies GSE has been shown to help break down stored fat from fat cells (lipolysis) as well as reduce food intake.  The effect of GSE on food intake in humans was tested over a three day period in a variety of people of different body composition and age.  Those who were overweight18 had a four percent reduction in food intake.  This preliminary study suggests that GSE will help an overweight person’s willpower to eat less food should they decide to cut back on calorie intake.

The really exciting news is what GSE is doing at the gene level in relationship to fat, inflammation, diabetes, cholesterol, and triglycerides.

It is well known in human physiology19 that fat produces hormone messengers such as leptin and adiponectin as well as inflammatory signals such as TNFa and IL6.  It is also known that once inflammation starts in fat, it turns on your liver’s production of CRP, another inflammatory messenger.  Excess and low-grade CRP, TNFa, and IL6 are all associated with increased risk for cardiovascular disease.  This inflammatory situation is accompanied by high levels of leptin in your blood (leptin resistance), high triglycerides, high cholesterol, and low adiponectin.  As adiponectin drops low then insulin resistance is caused in the liver, eventually resulting in type 2 diabetes.  Correcting leptin problems by following the Leptin Diet, exercising, and using dietary supplements that foster improved leptin function go a long way toward fixing this problem.  Of course, any nutrient that boosts adiponectin and lowers these inflammatory messengers will not only improve metabolism to assist weight management but also reduce the risk for heart disease.

A recent animal study induced this exact metabolic problem profile by feeding rats a high fat diet.  The researchers found that GSE reversed the metabolic problems20, lowering the inflammatory signals CRP, IL6, and TNFa.  Of great importance, the GSE boosted the production of adiponectin, indicating that GSE can help prevent metabolic deterioration to the point of type 2 diabetes. 

Novel animal research is showing that GSE helps your liver clear cholesterol21 and turns on fat burning gene signals that help lower triglycerides22.  While excess food consumption will overload these mechanisms, those who follow the Leptin Diet and exercise are likely to get a nice metabolic enhancement by consuming GSE as part of their weight management program.

One of the main problems that causes LDL cholesterol to wind up in plaque is that it is damaged (oxidized by free radicals or toxins), at which point it is taken up by macrophages and brought into the lining of arteries.  One key to cardiovascular health is preventing the damage to LDL.  GSE is a water-soluble nutrient and is not found in LDL, thus it is not directly protecting the membrane of LDL as do fat soluble antioxidants like tocotrienols, carotenes, Q10, and R-alpha lipoic acid.  Rather, GSE acts as an antioxidant police force in the circulatory fluid (blood plasma) and interstitial fluid of the arterial wall.  Research shows that GSE directly reduces the oxidation of LDL cholesterol by helping prevent free radicals from punching the LDL in the nose.

In 2000 a study of 40 people with high cholesterol found that a combination of 100 mg GSE twice a day and 200 mcg chromium twice a day lowered LDL cholesterol23 by 20 percent.  The GSE also cut autoantibodies to oxidized LDL cholesterol in half, compared to the control group (indicating cholesterol was less likely to be forming plaque in the GSE supplemented group).  Interestingly, these doses of both nutrients are on the conservative side.


Grape seed extract is a powerful protector of your heart and general circulation.  It favorably changes a number of metabolic signals toward reduced risk for cardiovascular disease.  It is proven to act as a water-soluble antioxidant and helps lower key inflammatory signals such as CRP, IL6, and TNFa.  It is also proven to act at the gene transcription level, helping clear cholesterol, reduce triglycerides, and directly helping the key inflammatory gene signal known as NF-kappaB. As far as GSE is concerned, the higher the dose the greater the protection. 

GSE is one of the marvels of Mother Nature.


Referenced Studies:
  1. ^ Red Wine Proanthocyanidins and Longevity  Nature  R. Corder, W. Mullen, N. Q. Khan, S. C. Marks, E. G. Wood, M. J. Carrier1 & A. Crozier.
  2. ^ Red Wine Reduces Fat Intake From a Meal  International Journal of Obesity  S Pal, M Naissides and J Mamo.
  3. ^ Grape Seed Extracts Relax Blood Vessels  Ann N Y Acad Sci.  Fitzpatrick DF, Bing B, Maggi DA, Fleming RC, O’Malley RM.
  4. ^ Grape Seed Extract Helps Relax Your Circulation  Clin Sci (Lond).  Edirisinghe I, Burton-Freeman B, Tissa Kappagoda C.
  5. ^ Grape Seed Extract has Potent Anti-Inflammatory Properties  J Agric Food Chem.  Terra X, Valls J, Vitrac X, Mérrillon JM, Arola L, Ardèvol A, Bladé C, Fernandez-Larrea J, Pujadas G, Salvadó J, Blay M.
  6. ^ Grape Seed Extract Promotes Dental Health While Protecting Circulation  J Periodontol.  Houde V, Grenier D, Chandad F.
  7. ^ Grape Seed Extracts Reduce Platelet Stickiness   J Cardiovasc Pharmacol.  Vitseva O, Varghese S, Chakrabarti S, Folts JD, Freedman JE.
  8. ^ Grape Seed Extract Helps Platelets of Male Smokers  J Med Food.  Polagruto JA, Gross HB, Kamangar F, Kosuna K, Sun B, Fujii H, Keen CL, Hackman RM.
  9. ^ Grape Seed Extract Protects Heart from Toxicity  Life Sci.  Karthikeyan K, Sarala Bai BR, Niranjali Devaraj S.
  10. ^ Grape Seed Extract Inhibits Growth of Candida Albicans  Phytomedicine.  Han Y.
  11. ^ Grape Seed Extract Protects Against Lead Exposure  Pak J Biol Sci  Badavi M, Mehrgerdi FZ, Sarkaki A, Naseri MK, Dianat M.
  12. ^ Grape Seed Extract Protects Heart Cells  J Agric Food Chem.  Du Y, Guo H, Lou H.
  13. ^ Grape Seed Extract Protects Heart from Extreme Toxicity  Eur J Pharmacol.  Du Y, Lou H.
  14. ^ Grape Seed Extract Protects the Heart in Diabetes  J Cardiovasc Pharmacol.  Cheng M, Gao HQ, Xu L, Li BY, Zhang H, Li XH.
  15. ^ Grape Seed Extracts Inhibit Glycation Damage in Circulatory System  J Cardiovasc Pharmacol.  Zhang FL, Gao HQ, Shen L.
  16. ^ Grape Seed Extract Reduces Alzheimer’s Plaque  The Journal of Neuroscience  Jun Wang, Lap Ho, Wei Zhao, Kenjiro Ono, Clark Rosensweig, Linghong Chen, Nelson Humala, David B. Teplow, and Giulio M. Pasinetti.
  17. ^ Grape Seed Extracts Protect Against UV Sun Damage  Free Radic Biol Med.  Mantena SK, Katiyar SK.
  18. ^ Grape Seed Extract Reduces Food Intake in Overweight Humans  Eur J Clin Nutr.  Vogels N, Nijs IM, Westerterp-Plantenga MS.
  19. ^ How Obesity Leads to Type II Diabetes is Now Very Clear  Int J Obes (Lond).   Zamboni M, Di Francesco V, Garbin U, Fratta Pasini A, Mazzali G, Stranieri C, Zoico E, Fantin F, Bosello O, Cominacini L.
  20. ^ Grape Seed Extract Lowers Inflammation and Boosts Adiponectin  Nutr Biochem.  Terra X, Montagut G, Bustos M, Llopiz N, Ardèvol A, Bladé C, Fernández-Larrea J, Pujadas G, Salvadó J, Arola L, Blay M.
  21. ^ Grape Seed Extracts Help Your Liver Clear Cholesterol  FASEB J.   Del Bas JM, Fernández-Larrea J, Blay M, Ardèvol A, Salvadó MJ, Arola L, Bladé C.
  22. ^ Grape Seed Extracts Help Turn On Gene Signals that Lower Triglycerides  Mol Nutr Food Res.  Del Bas JM, Ricketts ML, Baiges I, Quesada H, Ardevol A, Salvadó MJ, Pujadas G, Blay M, Arola L, Bladé C, Moore DD, Fernandez-Larrea J.
  23. ^ GSE and Chromium Help Lower Cholesterol in Humans  J Med.  Preuss HG, Wallerstedt D, Talpur N, Tutuncuoglu SO, Echard B, Myers A, Bui M, Bagchi D.

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