Grape Seed Extract supplement benefit and side effects
Medical uses and review for cancer, cholesterol and blood pressure research studies
Dosage and how much to take

February 17 2018 by Ray Sahelian, M.D.

Grape seed extracts have compounds called procyanidolic oligomers (PCOs). Other sources of PCOs are berries, green and black teas, and red wine. PCOs are powerful antioxidants, perhaps greater than vitamins C and E. They also inhibit a number of enzymes that degrade connective tissue such as elastase, collagenase, and hyaluronidase.

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Grape Seed Extract is a natural plant product made from the grape seed (or pip). Grape Seed Extract is rich in procyanidins, a special class of water-soluble bioflavonoids which are excellent free radical scavengers.



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Suggested Use, how much to take: 1 to 2 grape seed extract tablets a few times a week, or as recommended by your health care professional.
Q. One website online says this of grape seed extract and some other supplements: This is a temporary use supplement only for 6 to 12 months. Do you agree?
   A.  Much depends on the person, the dosage used, one's diet, other supplements taken, medications taken, weight, etc. As a general rule I prefer people take occasional breaks from the use of most supplements.

Benefit of Grape Seed extract supplement
The primary clinical indications are the treatment of such vascular disorders as venous insufficiency and capillary fragility and possibly retinal maladies such as diabetic retinopathy and macular degeneration. PCOs may improve night vision.

Moderately high amounts of grape seed extract may blunt salt-sensitive hypertension.
Grape seed extract may be helpful as an antioxidant in smokers.

According to one study, grape seed extract does not provide relief for symptoms such as stuffy nose, sneezing and itchy, and watery eyes.

Alzheimer's disease
Bioorg Med Chem Lett. 2013. Gallic acid is the major component of grape seed extract that inhibits amyloid fibril formation. Many protein misfolding diseases, for example, Alzheimer's, Parkinson's and Huntington's, are characterised by the accumulation of protein aggregates in an amyloid fibrillar form. Natural products which inhibit fibril formation are a promising avenue to explore as therapeutics for the treatment of these diseases. In this study we have shown, using in vitro thioflavin T assays and transmission electron microscopy, that grape seed extract inhibits fibril formation of kappa-casein (κ-CN), a milk protein which forms amyloid fibrils spontaneously under physiological conditions. Among the components of grape seed extract, gallic acid was the most active component at inhibiting κ-CN fibril formation, by stabilizing κ-CN to prevent its aggregation. Concomitantly, gallic acid significantly reduced the toxicity of κ-CN to pheochromocytoma12 cells. Furthermore, gallic acid effectively inhibited fibril formation by the amyloid-beta peptide, the putative causative agent in Alzheimer's disease. It is concluded that the gallate moiety has the fibril-inhibitory activity.

Cancer prevention
Mutat Res. 2014. Free radical scavenging, antioxidant and cancer chemoprevention by grape seed proanthocyanidin: an overview.

Cataract eye disease
J Nutr Health Aging. 2014. Grape seed extract and zinc containing nutritional food supplement prevents onset and progression of age-related cataract in wistar rats.

Oral intake of proanthocyanidin-rich extract from grape seeds improves chloasma.
Phytother Research 2004.
Chloasma (melasma) is often recalcitrant to various treatments and an amenable, as well as safe, pigment-reducing modality is needed. We investigated that the reducing effect of proanthocyanidins on chloasma in a one-year open design study. Proanthocyanidin-rich grape seed extract was orally administered to 12 Japanese woman candidates with chloasma for 6 months between August 2001 and January 2002 and to 11 of these 12 for 5 months between March and July 2002. Clinical observation, L* value (lightening) and melanin index, and size (length and width) measurements of chloasma were performed throughout the study period. The first 6 months of grape seed extract intake improved or slightly improved chloasma in 10 of the 12 women and following 5 months of intake improved or slightly improved chloasma in 6 of the 11 candidates. L* values also increased after grape seed extract intake. Melanin-index significantly decreased after 6 months of the intake, and also decreased at the end of study. Grape seed extract is effective in reducing the hyperpigmentation of women with chloasma. The beneficial effects of grape seed extract was maximally achieved after 6 months and these was no further improvement after this period. The latter grape seed extract intake for 5 months may prevent chloasma from becoming worse prior to the summer season.

Cholesterol, Effect of a standardized grape seed extract on low-density lipoprotein susceptibility to oxidation in heavy smokers.
Metabolism. 2003.
The aim of our study was to evaluate the effect of a standardized formulation of a polyphenolic extract of grapes (Leucoselect-Phytosome) on low-density lipoprotein (LDL) susceptibility to oxidation in a group of heavy smokers. A randomized, double-blind, crossover study was undertaken in 24 healthy male heavy smokers, aged > or = 50 years. Enrolled subjects were given 2 capsules twice daily for 4 weeks (phase 1). Each capsule contained 75 mg of a grape procyanidin extracts and soy-phosphatidlcholine or placebo consisiting of 75 mg lactose and soy-phosphatidlcholine. A wash out period of 3 weeks was then followed by 4 weeks of the opposite treatment (phase 2). Blood samples were taken at baseline and at the end of each phase and assayed for plasma lipids and LDL susceptibility to oxidation. Compliance was good, and no adverse effects were recorded. Subjects did not show significant modification of total cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C) and LDL-C during LP treatment. Among oxidative indices, thiobarbituric acid reactive substances (TBARS) concentration was significantly reduced in subjects taking grape seed extract, and the lag phase prolonged compared with placebo and basal values. The antioxidant potential of these polyphenols may prove effective in a model of oxidative stress (smoking); however more investigational data are needed before use in wider clinical settings.

Hypertension, high blood pressure, how to lower
Cardiovascular researchers at UC Davis, School of Medicine, completed the first human clinical trial to study the benefits of grape seed extract on patients with high blood pressure. The one month study was done on 24 male and female patients diagnosed with metabolic syndrome, which is a combination of factors that add up to high risk for heart disease, including elevated blood pressure, excess abdominal body weight, high blood cholesterol fats, and high blood sugar. The patients were divided into three groups of eight. The first group received a placebo while the second and third groups received 150 mgs and 300 mgs, respectively, of a grape seed extract developed and made by Polyphenolics, a division of Constellation Wine US. All participants' blood pressure was automatically measured and recorded for 12 hours after grape see extract ingestion. Participants in the two groups receiving grape seed extract experienced an average drop in systolic pressure or 12 mm and diastolic pressure 8 mm compared to placebo.
  Dr. Sahelian says: This is encouraging news regarding the role of grape seed extract and blood pressure. It would seen a good idea to take 100 mg a day of grape seed extract with medical supervision and monitoring of BP.

Medicine (Baltimore) 2016. The impact of grape seed extract treatment on blood pressure changes: A meta-analysis of 16 randomized controlled trials. Our findings demonstrate that grape seed extract exerted a beneficial impact on blood pressure, and this impact was more obvious in younger or obese subjects, as well as in patients with metabolic disorders.

Br J Nutrition 2016. Effects of grape seed extract beverage on blood pressure and metabolic indices in individuals with pre-hypertension: a randomised, double-blinded, two-arm, parallel, placebo-controlled trial. The aim of the present study was to test grape seed extract (GSE) as a functional ingredient to lower blood pressure (BP) in individuals with pre-hypertension. A total of thirty-six subjects were randomised to Placebo or GSE groups;. Subjects consumed a juice containing 0 mg or 300 mg/d GSE 150 mg twice daily for 6 weeks. GSE significantly reduced systolic BP (SBP) by 5 % and diastolic BP (DBP) by 4 % after 6 weeks of intervention period, which was significantly different from Placebo. BP returned to baseline after the 4-week discontinuation period of GSE beverage. Subjects with higher initial BP experienced greater BP reduction; nearly double the effect size. Fasting insulin and insulin sensitivity tended to improve after 6 weeks of GSE beverage supplementation; no significant changes were observed with fasting plasma lipids, glucose, oxidised LDL, flow-mediated dilation or vascular adhesion molecules. Total plasma phenolic acid concentrations were 16 times higher after 6 weeks of GSE v. Placebo. GSE was found to be safe and to improve BP in people with pre-hypertension, supporting the use of GSE as a functional ingredient in a low-energy beverage for BP control.

Skin cancer
Chemicals found in grape seeds may help ward of skin cancer due to regular exposure to the sun. Researchers from the University of Alabama, Birmingham exposed hairless mice to ultraviolet-light. Some of the mice they fed a standard diet supplemented with grape seed proanthocyanidins, while control mice were fed a standard diet without this supplement. Dietary supplementation with grape seed extract inhibited light-induced carcinogenesis, study. Mice supplemented with grape seed extract had up to 65 fewer skin cancer tumors than control mice did. Moreover, the tumors seen in grape seed extract -supplemented mice were smaller than those seen in the control mice. Grape seed extracts appear to inhibit suppression of the immune system caused by ultraviolet light. Grape seed extract has antioxidant activity, and UV-induced oxidative stress has been linked to the induction of skin cancers.

Menopause help
Menopause 2014. Effects of grape seed proanthocyanidin extract on menopausal symptoms, body composition, and cardiovascular parameters in middle-aged women: a randomized, double-blind, placebo-controlled pilot study. This study aims to assess the effects of proanthocyanidin-a class of polyphenol antioxidants extracted from grape seeds-on menopausal symptoms, body composition, and cardiovascular parameters in middle-aged women. We conducted a randomized, double-blind, placebo-controlled study in 96 women aged 40 to 60 years who had at least one menopausal symptom. The study participants were randomized to receive grape seed extract tablets containing either low-dose (100 mg/d) or high-dose (200 mg/d) proanthocyanidin, or placebo, for 8 weeks. Their menopausal symptoms were evaluated using the Menopausal Health-Related Quality of Life Questionnaire, Hospital Anxiety and Depression Scale, and Athens Insomnia Scale before and after 4 and 8 weeks of treatment. Body composition and cardiovascular parameters were also measured. A total of 91 women (95%) completed the study. Background characteristics, including age, menopause status, subjective symptom scores, body composition, and cardiovascular parameters, were similar among the groups. The following significant changes were observed during the course of the study: (1) physical symptom score, hot flash score, and (2) Athens Insomnia Scale score decreased in the high-dose group after 8 weeks of treatment; (3) Hospital Anxiety and Depression Scale Anxiety score and (4) systolic and diastolic blood pressure decreased in the low-dose and high-dose groups after 4 weeks; and, (5) lastly, muscle mass increased in the low-dose and high-dose groups after 8 weeks of treatment. Grape seed proanthocyanidin extract is effective in improving the physical and psychological symptoms of menopause while increasing muscle mass and reducing blood pressure in middle-aged women.

Grape Seed extract is sold in various extract potencies, including 95 percent proanthocyanidins or 95 percent polyphenols. I have not had a chance to evaluate the benefits of grape seed oil.

Grape seed extract side effects, safety, caution, risk
Grape seed extract side effects have not been reported in the medical literature, but very few human studies have been done. In one study with cancer patients given radiation therapy and grape seed extract 100 mg three times a day orally for 6 months, no major adverse reaction were reported.

Polyphenolics in grape seeds-biochemistry and functionality.
J Med Food. 2003.
Grape seeds are waste products of the winery and grape juice industry. These seeds contain lipid, protein, carbohydrates, and 5-8% polyphenols depending on the variety. Polyphenols in grape seeds are mainly flavonoids, including gallic acid, catechin, epicatechin, gallocatechin, epigallocatechin, and epicatechin 3-O-gallate, and procyanidin dimers, trimers, and more highly polymerized procyanidins and proanthocyanidins which have many times the antioxidant power than vitamins E and C. Extensive research suggests that grape seed extract is beneficial in many areas of health because of its antioxidant effect to bond with collagen, promoting youthful skin, cell health, elasticity, and flexibility. Other studies have shown that proanthocyanidins help to protect the body from sun damage, to improve vision, to improve flexibility in joints, arteries, and body tissues such as the heart, and to improve blood circulation by strengthening capillaries, arteries, and veins.

Grape seed extract activates Th1 cells in vitro.
Clin Diagn Lab Immunol 2002.
We hypothesize that the flavonoid constituents of a proprietary grape seed extract that contains procyandins exert significant antiviral and antitumor effects, by inducing production of the Th1-derived cytokine gamma interferon (IFN-gamma) by peripheral blood mononuclear cells) from healthy donors. Our results show that grape seed extract significantly induced the transcription of IFN-gamma mRNA as demonstrated by reverse transcription-PCR but had no effect on the Th2-derived cytokine interleukin-6. The enhancing effect of grape seed extract on IFN-gamma expression was further supported by a concomitant increase in the number of cells with intracytoplasmic IFN-gamma as well as the synthesis and secretion of IFN-gamma. Our results demonstrate that the potentially beneficial immunostimulatory effects of grape seed extract may be mediated through the induction of IFN-gamma.


Q. I am wondering if grape seed extract supplement should be standardized to 95% polyphenols. I notice that many herbal products do not seem to be standardized. Thanks for your time and your newsletter is right on.
   A. Since there are no long term human studies with grape seed extract, it is anybody's guess as to the ideal extract potency. Also, there are few herbs that have been studied in an accepted standardized form. Little is known as to whether a certain standardized extract is better than the whole herb or a different extract potency. With all these uncertainties, no definite guidelines can be given.

Q. My husband and I both have tended to suffer from frequent morning migraines. We do not drink alcohol. One Grapeseed extract before bedtime has cut these occurrences at least 90% or more. It's been miraculous. I first discovered this unmistakable phenomenon and got my husband on them and now we make sure we take it before bedtime. "Did you take your Grapeseed extract? I started taking them because he read somewhere that it helped promote better sleep, a problem more for me than him and it does that as well. Like I said, the biggest unexpected boon is the migraine prevention. We both had true migraines. All day and very debilitating and a ton of over the counter pain killer sometimes just barely took the edge off (if lucky). Mine were generally gone by evening, but I was losing a day at least 2 times a week. His could go on into the next day. So we're healthier because now we are not pouring Ibuprofen, aspirin and acetaminophen into our systems on a regular basis. On the rare occasion that a migraine starts to happen, we have both found that 1 advil (instead of the previous 4) plus 1 grapeseed banishes it. Once in while, up to 3 or 4 grapseed extract pills works alone once a migraine has grabbed hold but not usually. Then the 1 or 2 grapeseed and 1 advil works. The best thing is prevention, so it is an indispensible herb for us both before bed.
   A. This is interesting. What brands were they, was it only grape seed extract or combined with other herbs?
      Q. Spring Valley and the CVS Brand are 2 we've used recently. There are other ingredients in the last 2 or so bottles we've purchased, but I have received the same effect from plain grapeseed extract which was what I initially used. So many brands now have other ingredients added that at first we wondered if it would work the same. It does. Right at the moment the brand is: Spring Valley Grapeseed plus Resveratol. Purchased at Walmart. Selenium - 15mcg, Grapeseed Extract - seed and skin standardized to contain polyphenols - 50mg. Antioxidant blend: Green tea, Citrus bioflavinoids, Bilberry - 130mg. I started with two at night, but have found that if I take them regularly, just one before bed does the trick.

Q. I have been taking grape seed extract on and off for several months, and really believe it has helped very stubborn warts I have on a finger and a thumb. However, when I get frequent side effects such as digestive problems like reflux, sour stomach, bloatedness, I quit taking it thinking these symptoms are grape seed extract side effects. I really don't know that it does cause it, could be stress I have been under. I would like to take the grape seed extract supplement for 3 months regularly and am sure I would see results about the warts. Have you had any reports of grape seed extract supplement causing digestive disturbances? I take Vitamin Shoppe100 mg (one a day) which contains no other herbs, etc. I do enjoy your website, newsletters, etc. so much and fully rely on them rather than any other one.
   A. We are not aware of long term human studies with grape seed extract supplements. Thus far we have not had reports of grape seed extract side effects, but we cannot rule out that this grape seed extract supplement may cause gastrointestinal symptoms. Much is still unknown about the benefits and side effects of long term use of various herbs and herbal extracts.

Q. I've been taking it for years, it has gotten rid of my facial brown spots, most wrinkles, my hair shines, etc. I am 50 years old but I look 35!
   A. I have not seen any long term studies with grapeseed extract supplements to know whether whether this product would be effective and safe for long term use in vast numbers of people and whether it has anti-aging potential.

I have a question about grape seed extract and have bought some in the liquid form which I add as drops to water. I would appreciate to know how many drops of, say, 33% GSE are equivalent to one tablet of your GSE 100 mg product. Do you have any opinion about whether to use diluted drops or tablets? Drops would seem to offer more flexibility of dosage strength, particularly for external use.
    We have no idea of the quality and potency of the liquid form, and how it was manufactured, to know the equivalencies between the oral form and the liquid form.

Someone said to me that extracts have no oil. But if they come from a seed, like grape seed, or olive, grapefruit seed or whatever, you can make oil from the seeds, right? And, you can make extract, right? So would the extract have oil in it?
    It depends on the process of extraction and manufacturing, but some extracts could have oil in them, for instance pumpkin seed oil extract.

Other products online
Natural Factors, GrapeSeedRich, Grape Seed Extract, 100 mg, 90 Veggie Caps

Supplement Facts
Serving Size: 1 Capsule
  Amount Per Capsule % Daily Value
GrapeSeedRich (Vitis vinifera) extract 100:1 (seed) 100 mg **
Polyphenols (95%) 95 mg **
** Daily Value not established.

Supplement Facts
Grape Seed Extract 100 mg
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