Grape Juice, Purple

Scientific Name(s): Vitis vinifera L., Vitis labrusca L., Vitis rotundifolia Michx. Family: Vitaceae

Common Name(s): European or “Old World” grapes (95% of grapes) V. vinifera , American bunch grapes ( V. labrusca ), muscadine grapes ( V. rotundifera )

Uses

Purple grape juice may possess beneficial cardiac effects, with endothelial function improving in most clinical studies. Antimicrobial, antioxidant, and immune system effects have been demonstrated in vitro and in animal studies, and a role in the prevention of cancer and memory improvement in elderly patients is being evaluated.

Dosing

Cardiac disease: A wide variety of test doses from 4 mL of grape juice/kg to 18 mL/kg daily and durations from 14 days to 12 weeks were used in trials.

Contraindications

Aside from allergy to grapes, none have been identified.

Pregnancy/Lactation

Generally recognized as safe (GRAS) when used as food. Avoid dosages above those found in food because safety and efficacy are unproven.

Interactions

Decreased area under the curve (AUC) and maximum plasma concentration (C max ) for cyclosporine were shown in healthy volunteers given purple grape juice; avoid the combination.

Adverse Reactions

Allergy, increased serum-fasting insulin levels, and acidic saliva have been reported. Grape juice may have a mild laxative effect.

Toxicology

Information is lacking.

Botany

Grapes grow in bunches of 6 to 300 grapes on woody, climbing vines and come in a variety of colors, including black, blue, golden, green, red, white, and purple. V. vinifera is a deciduous climber with several stems, tendrils, clusters of pale-green flowers, and palm-shaped leaves. French hybrid varieties of grapes were developed mainly for wine making. Grapes are native to southern Europe and western Asia but are cultivated in temperate regions throughout the world. 1 , 2 , 3

History

Grape leaves have been seen in fossils dating back to prehistoric times. Grapes were domesticated in western Asia before 5,000 BC and have been mentioned in biblical writings and depicted in tomb paintings dating to 2,400 BC. Circa 1635, Jesuit priests brought Spanish grapes to Mexico, establishing vineyards in what is now Socorro, New Mexico, the area of the earliest planting of grapes in the United States. In 1652, the English herbalist Nicholas Culpeper recommended grapes as a mouthwash. In the 1850s, California became involved in grape cultivation. In 1927, the eclectic physician A.M. Liebstein mentioned grapes as being beneficial for dyspeptic and febrile conditions, liver and kidney ailments, tuberculosis, hemorrhoids, varicose veins, osteomyelitis, gangrene, and cancer. In The Grape Cure published in 1928, the author Johanna Brandt claimed that grapes had cured her stomach cancer. 4 In general, grapes are nourishing and have a mildly laxative effect. Red grape leaves have astringent and anti-inflammatory effects. Red leaves and grapes have been used in the treatment of varicose veins, hemorrhoids, and capillary fragility. 2 , 3

Chemistry

Grapes are approximately 80% water and contain 70 calories per 100 g, with a carbohydrate content of approximately 16%. Commercial grape juice is lower in sucrose than other fruit juices, 5 and other sugars, amino acids, and organic acids in grape juice and wines have been identified. 6 The amino acid arginine is abundant in grape juice. 7 Grapes contain tartaric and carboxylic acids, including malic, citric, lactic, succinic, and shikimic acids. 3 , 8 Vitamins A, B 1 , B 2 , and C also are present in grapes, as are minerals, including chromium and potassium. 3 Anthocyanins are found in grapes with red pigments, as well as in other pigmented fruits. A review discussing anthocyanins in grapes, juices, and wines is available. 9 , 10

Flavonoids, including quercetin, catechins, myricetin, and kaempferol, are important constituents in purple grape juice. 11 , 12 Certain flavonoids present in purple grape varieties possess beneficial actions not seen in other varieties, and the juice is different from grape wine (see the Wine monograph) . 13 Grape juice is the fluid expressed from ripened grapes, including the nutrients in the crushed grape seeds, which is then passed through a separator, treated, and pasteurized. 13 Catechin concentrations are substantial in red wine (27 to 96 mg/L) but low to negligible in white wine and commercially available grape juices tested in another report. 14 Other constituents found in grapes include tannins, inositol, choline, and pectin. 3 Glutathione and thiol-containing compounds have been found in the juice. Isomers of resveratrol in grape juice and wine also are present, as are antioxidants. 13 , 14 , 15

Uses and Pharmacology

Cardiovascular function

Beneficial cardiac effects attributed to purple grape juice are largely considered to be due to the polyphenol flavonoid content. In addition, the phenol resveratrol may also be relevant in hypertension, heart failure, and ischemic heart disease, although there is insufficient evidence at this time to recommend long-term use of resveratrol at dosages higher than those obtained from usual dietary consumption. The content of resveratrol in purple grape juice and wine is low. 16 , 17 For a more detailed discussion of the clinical effects of resveratrol, see the Wine monograph .

Animal data

In vitro studies using porcine coronary artery have shown that purple grape juice induces endothelial-dependent vasodilation. 18 In rabbits and hamsters fed a high-cholesterol diet, purple grape juice for 12 to 13 weeks improved the lipid profile, decreased platelet aggregation, and decreased the formation of atheroma. 19 , 20 The study using rabbits showed a decrease in blood pressure and no increase in body weight compared with controls, 19 and the study with hamsters showed an increased plasma antioxidant capacity. 20 However, a similar study in rats found no change in total serum cholesterol after 5 weeks of grape juice administration and no protective effect on oxidative-induced liver damage, but did show improved antioxidant capacity in peripheral blood cells. 21

Clinical data

Studies have focused on the effects of grape juice on lipid profile, platelet aggregation, blood pressure, and brachial artery reactivity. Additionally, markers of inflammation and blood glucose have been documented. A wide variety of grape juices, test dosages (from 4  to 18 mL/kg daily), duration (14 days to 12 weeks), and study populations (healthy adults; hemodialysis patients; patients with hypercholesterolemia, hypertension, coronary artery disease, type 2 diabetes, and metabolic syndrome) have been used in trials. 22 Improved lipid profiles were observed in hemodialysis patients after 2 weeks of grape juice supplementation 23 , 24 ; however, studies in patients with hypercholesterolemia, 25 mild hypertension, 26 or type 2 diabetes 27 and healthy adults 28 found no change in plasma lipids with 2 to 12 weeks of grape juice supplementation. Platelet aggregation was reduced in some, 29 , 30 but not all, studies. 25 In studies of mild hypertension, there was no effect on ambulatory blood pressure, but a decrease in nocturnal systolic pressure was found in one study 31 and small (6 to 7 mm Hg) decreases were found in another. 26 Endothelial function in patients with metabolic syndrome, 32 hypercholesterolemia, 25 and coronary artery disease, 11 , 33 as well as in healthy adults, 34 improved with grape juice supplementation. However, these measures are largely surrogate markers for cardiac morbidity and mortality, and clinical trials evaluating direct outcomes are needed.

Cognition
Animal data

Rats fed purple grape juice showed improved motor function and cognition as demonstrated in the water maize test. 35

Clinical data

A small study evaluated the effect of 6 and 9 mL/kg/day of purple grape juice for 12 weeks in elderly participants with nondementia memory lapse. An improvement in verbal learning and retention was demonstrated; however, no improvement was shown in nonverbal memory or symptoms of depression. 36

Other uses
Antimicrobial

Purple grape juice demonstrated inhibitory activity against Escherichia coli and Cronobacter sakazakii in vitro. 37 , 38 The juice used as a mouth rinse led to a decrease in bacteria adhering to teeth; however, the resultant erosive pH precludes this application. 39

Antioxidant

Hepato- and brain–tissue-protective effects against carbon tetrachloride– and radiation-induced oxidative damage have been demonstrated in rats fed purple grape juice. 40 , 41 , 42 , 43

Cancer

Limited animal studies have been conducted to demonstrate protective effects of purple grape juice on induced cancers. Focus has centered on the activity of anthocyanins, resveratrol, and other polyphenols. 42 , 44 , 45

GI

A pilot study evaluated the effect of purple grape juice on chemotherapy-induced nausea and vomiting. A trend toward an effect was found; however, the dropout rate was too high to calculate significance. 46

Immune effects

Purple grape juice upregulates the immune system in animal models; however, clinical studies are lacking. 47 A study in healthy adults demonstrated increased circulating T cells and improved serum antioxidant capacity with purple grape juice over 9 weeks. 48

Dosage

Cardiac disease

A wide variety of test dosages from 4  to 18 mL/kg of grape juice daily in divided doses and durations from 14 days to 12 weeks were used in trials. 24 , 25 , 26 , 27 , 28 , 31 , 32 , 33 , 34 Efficacy of these dosages is not yet proven.

Pregnancy/Lactation

GRAS when used as food. Avoid dosages above those found in food because safety and efficacy are unproven.

Interactions

Case reports of interactions with purple grape juice are lacking. In vitro studies demonstrate an effect on cytochrome P450 (CYP-450) 2C9 and CYP3A; however, no effect on flurbiprofen (suggested as a marker of warfarin) was found for CYP2C9, 49 and grapes were less inhibitory than grapefruit on CYP3A activity. 50 In healthy volunteers, no influence on the pharmacokinetics or pharmacodynamics was found, 51 whereas a decreased AUC and C max for cyclosporine was shown, suggesting the need to separate purple grape juice dosage by at least 2 hours from cyclosporine. 52

Adverse Reactions

Case reports exist of immunoglobulin E–mediated allergy, including severe anaphylaxis to grapes and grape products. 53 Clinical studies have found increases in serum-fasting insulin, possibly due to an increased carbohydrate load. 13 , 36 Grape juice is more acidogenic than orange and pineapple juices, and regular consumption may contribute to the erosion of tooth enamel. 39 , 54 Grape juice may be mildly laxative.

Toxicology

Research reveals little or no information regarding toxicity with the use of purple grape juice.

Bibliography

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40. Dani C, Pasquali MA, Oliveira MR, et al. Protective effects of purple grape juice on carbon tetrachloride-induced oxidative stress in brains of adult Wistar rats. J Med Food . 2008;11(1):55-61.
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