Grape seed extract is mostly used for its antioxidant qualities and for its numerous cardioprotective and circulatory benefits. Recently grape seed extract attained GRAS status with the FDA and due to this it is expected to become more popular in functional foods. The active constituents of grape seed extract are proanthocyanidins, the procyanidin oligomers (PCOs). Grape seed or PCO extracts normally contain a mixture of PCOs of different lengths (dimers, trimers, tetramers and oligomers of up to 7 units).
Grape seed extract has been confirmed in both preclinical and clinical studies to be a potent antioxidant, and it has good clinical evidence of its usefulness in preventing and ameliorating cardiovascular and circulatory disorders. Grape seed extract and the PCOs from grape seed have been studied in animals and in vitro to confirm the cardioprotective, circulatory and antioxidant benefits found from traditional use. Some of the key preclinical studies are listed below:
•Rabbits fed grape-seed extracts in cholesterol-enriched diets showed significant decrease in cholesteryl ester hydroperoxides compared to the controls fed cholesterol-enriched diets alone. The rabbits in the grape seed extract group also showed significantly fewer atherosclerotic plaques in their aortic arch, a significant decrease in the total cholesterol and malondialdehyde (MDA) contents in the aortic arch and thoracic aorta, and a decrease in the number of foam cells in oxidized low-density lipoprotein (LDL)-positive cells of the atherosclerotic lesions (Yamakoshi et al., 1999).
•The cardioprotective effects of PCOs were found to be mediated by: a) scavenging of oxygen-centered radicals (hydroxyl and peroxyl); and b) sequestration of the cations Fe+2 and Cu+2, which enhance the formation of harmful hydroxyl radicals when triggered by superoxide/hydrogen peroxide (Maffei Facinó et al., 1996).
•The cardioprotective benefits of grape seed extract was shown in rats. Compared to controls, the rats fed the grape seed extract showed a significantly faster recovery time from myocardial infarction, significantly smaller infarct mass and size and higher aortic flow (Sato et al, 1999).
•Jonadet et al. (1983) found that grape seed showed the highest in vitro elastase-inhibiting activities compared to bilberry and pine park. Elastase is involved with the destruction of elastic fibers and conjunctive tissue.
•Procyanidins from grape seed are known to inhibit lipid peroxidation because they are effective scavengers of superoxide anion, hydroxyl radical anion, and lipid peroxyl radicals (Maffei Facinó et al., 1996; Meunier et al., 1989).
•Procyanidins also indirectly have antioxidant functions by inhibiting oxidation of low-density lipoprotein (LDL) catalyzed by Cu+2 (Frankel et al., 1993).
Grape seed is a good example of a non-toxic (GRAS) botanical that has several benefits in supplementing the diet. It has been confirmed use as an antioxidant as a cardioprotective and for circulatory health, and would make an excellent daily addition to the standard American diet.
Peripheral Vascular Benefits
Retinopathies were studied by a) a controlled study of 75 patients with ocular stress caused by a visual display unit, and b) another study of 91 myopic patients. Procyanidins (300 mg/day for 60 days) caused significant improvement of subjective symptoms and contrast sensitivity relative to the control group in study a). In the second study b) retinal function was reported to have improved from administration of 300 mg/day of procyanidins for 28 days (Bombardelli and Morazzoni, 1995).
A double-blind, placebo-controlled study of 92 patients with peripheral venous insufficiency found procyanidins (300 mg daily for 28 days) effective in 75% of the patients. Procyanidin treatment was found to improve the functional measures (pain, paresthesias, nocturnal cramps, edema, etc) of venous insufficiency by more than 50% (Bombardelli and Morazzoni, 1995).
Visual adaptation to low intensity light (night morphoscopic vision) and visual performance following glare was improved in patients given a grape seed extract (Endotelon®, 200 mg per day for 5 weeks). The study was placebo controlled and utilized 100 subjects without ophthalmological pathology (Corbe et al., 1988).
Lesbre and Tigaude (1983) conducted a randomized, placebo-controlled study in 20 patients diagnosed with capillary hyperpermeability and hepatic cirrhosis. The capillary fragility index in the patients given the grape seed extract (150 mg proanthocyanidins, two times a day for eight weeks) was significantly higher than placebo.
Sarrat (1981) conducted a study on 30 patients without varicose veins for the effect of grape seed extract (150 mg/30 days), diosamine (a semi-synthetic flavonoid product), or placebo on the possible indications that could develop into varicose veins later in life. The grape seed extract significantly lowered the occurrence of indications such as heaviness of the legs, cramps, itching, abnomal sensations such as burning and prickling and the sensation of swelling. The author concluded that grape seed extract might be effective in preventing varicose veins from developing.
In a double-blind study, grape seed extract (Endotelon®, 150 mg daily for 30 days) was compared against diosamine (450 mg/day for 30 days) for its effect on 50 female patients with chronic venous insufficiency (mostly pregnancy-related). Although both treatments were effective in reducing the symptoms of chronic venous insufficiency, grape seed extract showed a faster action that also lasted longer. Also, only 45% of the diosamine group became symptom-free compared to 65% of the grape seed extract group (Delacroix, 1981).
Royer and Schmidt (1981) showed in an preliminary study that a single oral dose of procyanidins increased objectively the venous tone in patients with widespread varicose veins.
The effect of procyanidins (150 mg/day) in 25 diabetic and hypertensive patients in a double-blind, placebo controlled study was investigated. Capillary resistance increased 23% in the treatment group. In another study of 28 diabetic and hypertensive patients, capillary resistance was found to increase 18% using a similar dose of procyanidins (Lagrue et al., 1981).
Dartenuc et al. (1980) conducted a double-blind study with standardized grape seed extract in 37 hospitalized patients with capillary fragility. Endotelon® was administered at the rate of 50 mg of proanthocyanidins two times daily over 15 days. In 10 out of 21 of the patients given the extract, and in 3 out of 12 on placebo, capillary resistance was improved.
A double-blind, placebo-controlled study of a standardized grape seed extract on 71 patients with peripheral venous insufficiency found grape seed extract to have a significant beneficial effect. Grape seed extract treatment (Endotelon®, 100 mg three times daily for 28 days) caused significant improvement in symptoms of nocturnal cramps, leg heaviness, edema and tingling. Improvements were found for 75% of the active treatment group compared to 41% on placebo) (Thébaut et al., 1978).
Visual acuity was improved or remained stable in 29 out of 30 patients diagnosed with atherosclerotic retinopathy. In this double-blind, placebo-controlled study, the patients were given 100 mg daily of proanthocyanidins for one year or placebo (Verin et al., 1978).
The antioxidant activity of grape seed extract (300 mg/day for 5 days of a standardized extract with 150 mg of grape procyanidins/capsule) was studied in 20 healthy, nonsmoking adults who all followed a standardized dietary pattern in a single-blinded, randomized, placebo-controlled crossover study. The mean total antioxidant capacity (TAC) of the serum of the treatment group was significantly improved compared to baseline, and showed no significant change in the placebo group (Nuttall et al., 1998).
Safety / Dosage
The dosage recommendation of grape seed extract (containing 80-85% procyanidin oligomers) depends on whether the treatment is for preventative or therapeutic purposes. For prevention, 50 mg is recommended (or 125 mg of a bound form such as PCO-phosphatdylecholine). For therapeutic purposes, the dosage should range between 150 and 30 mg. Procyanidins have been found to have a synergistic effect with Vitamin C (McKenna et al., 2001).
Mild and transient side effects have been found during clinical trials, including mild gastrointestinal discomfort, vertigo, nausea, allergic reactions and headaches. Some PCOs can produce a platelet antiaggretory activity, and therefore would be contraindicated for those on anticoagulant medications, for those about to enter surgery (McKenna et al., 2001).
Procyanidins are thought to be safe during pregnancy, as no teratenogenic effects were found in pregnant chicks, mice, or rabbits at doses ten times the normal, and no contraindications were found from clinical studies in humans. There is no safety data available on grape seed extract use during lactation (McKenna et al., 2001).
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EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS.