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Grape Juice

Scientific Name(s): Vitis labrusca L., Vitis rotundifolia Michx., Vitis vinifera L.
Common Name(s): American bunch grapes (V. labrusca), European or "Old World" grapes (V. vinifera), Muscadine grapes (V. rotundifolia)

Medically reviewed by Drugs.com. Last updated on Dec 21, 2022.

Clinical Overview

Use

Purple grape juice has potential beneficial cardiac effects, likely due to its antioxidant activity; endothelial function has improved in most clinical studies. Antimicrobial and immune system effects have been demonstrated in vitro and in animal studies. A potential role in improving memory and cognition in elderly individuals is also being evaluated.

Dosing

In a systematic review investigating the effects of grape juice on human health, grape juice was administered in dosage ranges of 4 to 18 mL/kg/day and 100 to 500 mL/day for 5 to 30 days, often in 2 divided doses. Cardiac disease/risk factors: A wide variety of test dosages have been used to evaluate effects of dietary supplementation with grape juice on various cardiovascular disease risk factors. Dosages have ranged from 4 to 18 mL/kg/day, often in divided doses (durations ranged from 2 to 8 weeks), in some studies, while other studies used grape juice dosages of 100 to 500 mL/day (durations of 2 to 12 weeks). However, efficacy of these dosages has not been proven. Urinary tract symptoms: A 3-month intervention of 240 mL/day of grape juice was used in a clinical trial that enrolled men with lower urinary tract symptoms.

Contraindications

Aside from allergy to grapes, no contraindications have been identified.

Pregnancy/Lactation

Purple grape juice has "generally recognized as safe" (GRAS) status when used as food. Avoid amounts greater than those found in food because safety has not been established.

Interactions

Decreased area under the curve (AUC) and maximum plasma concentration (Cmax) for cyclosporine occurred in healthy volunteers given purple grape juice, suggesting a need to separate purple grape juice consumption from cyclosporine dosing by at least 2 hours.

Adverse Reactions

Purple grape juice is generally well tolerated. Allergy, increased serum fasting insulin levels, and acidic saliva have been reported. Grape juice may also have a mild laxative effect.

Toxicology

No data.

Scientific Family

Botany

Grapes grow in bunches of 6 to 300 on woody, climbing vines and come in a variety of colors, including black, blue, gold, 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 winemaking. Grapes are native to southern Europe and western Asia but are cultivated in temperate regions throughout the world.(Chevalier 1996, Ensminger 1994, USDA 2012) Any mature grape variety can be used to make grape juice. V. labrusca, for example, has been used to make red, purple, and white grape juice across a number of studies.(Dani 2021, Haskell-Ramsay 2017, Zuanazzi 2019)

History

Grape leaves have been found in fossils dating back to prehistoric times. Grapes were domesticated in western Asia before 5000 BC and are mentioned in biblical writings and depicted in tomb paintings dating to 2400 BC. Jesuit priests first brought Spanish grapes to Mexico in the 1630s and established vineyards in what is now Socorro, New Mexico.

In 1652, English herbalist Nicholas Culpeper recommended grapes as mouthwash. In the 1850s, California became involved in grape cultivation. In 1927, eclectic physician A.M. Liebstein claimed grapes were 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, Johanna Brandt claimed that grapes had cured her stomach cancer.Carper 1988 In general, grapes are nourishing and have a mild laxative effect. Red grape leaves have been used for astringent and anti-inflammatory purposes, and red grape leaves and red grapes have been used in the treatment of varicose veins, hemorrhoids, and capillary fragility.Chevalier 1996, Ensminger 1994

Chemistry

Grapes are approximately 80% water (containing 70 calories per 100 g), with a carbohydrate content of approximately 16%. Commercial grape juice is lower in sucrose than other fruit juices,Yoon 1997 and additional sugars, amino acids, and organic acids in grape juice and wines have been identified.Linget 1998 The amino acid arginine is abundant in grape juice,Austin 2000 and grapes contain tartaric and carboxylic acids, including malic, citric, lactic, succinic, and shikimic.Chevalier 1996, Fuleki 1993 Vitamins A, B1, B2, and C are also present in grapes, as are minerals including chromium and potassium.Chevalier 1996 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.Koswig 1995, Mazza 1995

Flavonoids, including quercetin, catechins, myricetin, and kaempferol, are important constituents of purple grape juice.Stein 1999, Xu 2011 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).Willett 2007 Grape juice is expressed from ripened grapes, including nutrients in the crushed grape seeds, and is then passed through a separator, treated, and pasteurized.Willett 2007 Catechin concentrations are substantial in red wine (27 to 96 mg/L) but low to negligible in white wine and commercially available grape juices that were tested in one report.Park 2000

Other constituents found in grapes include tannins, inositol, choline, and pectin.Chevalier 1996 Glutathione and thiol-containing compounds have been found in the juice. Isomers of resveratrol in grape juice and wine are also present, as are antioxidants.Park 2000, Soleas 1995, Willett 2007

Uses and Pharmacology

Antimicrobial activity

Purple grape juice demonstrated inhibitory activity against Escherichia coli and Cronobacter sakazakii in vitro.(Kim 2009, Kim 2010) When used as a mouth rinse, the juice led to a decrease in bacteria adhering to teeth; however, the resultant erosive pH precludes this application.(Hannig 2009)

Antioxidant activity

Animal data

Liver- and brain tissue–protective effects against carbon tetrachloride– and radiation-induced oxidative damage have been demonstrated in rats fed purple grape juice.(Andrade 2011, Dani 2008, Dani 2008, Dani 2009)

Clinical data

Several small studies conducted between 1995 and 2012 and investigating consumption of grape juice in both healthy volunteers and subjects with various conditions were summarized in a systematic review investigating the effects of 100% fruit juice (expressed juice free of additives or fortifications) on human health. Grape juice dosage ranges were 4 to 18 mL/kg/day and 100 to 500 mL/day and, except for one single-dose study, were consumed for 5 to 30 days. The most commonly used grapes were Concord, but Bobal and Tempranill varieties were also tested. Grape juice was consistently observed to improve antioxidant capacity as measured by serum (ie, lipid peroxidation, catalase, glutathione reductase) and urine biomarkers in healthy participants, as well as in patients with cardiovascular conditions and those on renal dialysis.(Hyson 2015)

In 2 studies included in the review, endothelial function improved in adults with coronary artery disease and in adolescents with metabolic syndrome consuming grape juice (8 mL/kg/day for 14 days and 18 mL/kg/day for 30 days, respectively) compared with baseline. In 26 healthy men, 1 month of red grape juice (150 mL/day twice daily) resulted in significant increases in high-density lipoprotein (HDL) cholesterol and apolipoprotein B (P<0.001 and P<0.002, respectively). Data regarding beneficial effects of grape juice on hypertension and platelet aggregation, however, are equivocal. Negative clinical effects on cholesterol parameters have also been consistently observed, including increases in total cholesterol, triglycerides, insulin concentrations, and glucose metabolism. One exception was a significant reduction in fasting blood glucose (−2 mg/dL; P=0.03) observed in a typically understudied population of female and black prehypertensive subjects. The addition of vitamin E to 100% expressed grape juice did not offer further improvements in the studies that enrolled patients with coronary artery disease or renal disease. Data were limited regarding the role of grape juice in patients with cancer or cognitive dysfunction, or regarding the impact of intake on body weight and related metabolism.(Hyson 2015)

A randomized, placebo-controlled crossover trial conducted in Brazil with the juice of V. labrusca investigated the effects of both organic and conventional growing methods on bioactive constituents in the grapes, as well as the acute effects on lipid peroxidation in 30 healthy volunteers. Participants, the majority of whom were female, were asked to exclude polyphenol-rich foods (ie, fruit, vegetables, chocolate, tea, coffee) from their usual diet for 3 days before the intervention. Participants randomly consumed 400 mL of conventional grape juice, organic grape juice, or water (control) and then crossed over to each of the other 2 interventions after a 15-day washout period. When compared with control, both grape juices produced significant reductions in serum biomarkers of lipid peroxidation (P<0.05), and the organic grape juice provided a higher protection against serum lipid peroxidation than the conventionally grown grapes (P<0.05). The organic grape juice contained the lowest amount of total sugars and the highest phenolic content compared to conventionally grown grapes, whereas mineral content was higher in the latter. No adverse events were reported.(Toaldo 2015)

Cancer

Animal data

A methanol extract of V. vinifera leaves was shown to have cytotoxic activity alone and in combination with doxorubicin in HepG2 hepatic cancer cells.(Zainab 2016)

Limited animal studies have been conducted to evaluate the protective effects of purple grape juice on induced cancers. Focus has centered on the activity of anthocyanins, resveratrol, and other polyphenols.(Dani 2009, Jung 2006, Mertens-Talcott 2006)

Cardiovascular effects

Beneficial cardiac effects attributed to purple grape juice are largely considered to be due to its polyphenol flavonoid content. In addition, the phenol resveratrol may be relevant in hypertension, heart failure, and ischemic heart disease; however, there is insufficient evidence to recommend long-term use of resveratrol at dosages higher than those obtained from usual dietary consumption. The resveratrol content in purple grape juice and wine is low.(Smoliga 2011, Vang 2011) For a more detailed discussion of the clinical effects of resveratrol, see the Resveratrol monograph.

Animal data

In in vitro studies using porcine coronary artery, purple grape juice induced endothelial-dependent vasodilation.(Anselm 2007) In rabbits and hamsters fed a high-cholesterol diet, purple grape juice given for 12 to 13 weeks improved the lipid profile and decreased platelet aggregation and formation of atheroma.(Décordé 2008, Shanmuganayagam 2007) The study in rabbits showed a decrease in blood pressure and no increase in body weight compared with controls,(Shanmuganayagam 2007) and the study with hamsters showed an increased plasma antioxidant capacity.(Décordé 2008) A similar study in rats administered grape juice for 5 weeks found no change in total serum cholesterol and no protective effect on oxidative-induced liver damage; however, antioxidant capacity in peripheral blood cells was improved.(Aguiar 2011)

Clinical data

Studies have focused on grape juice's effects on lipid profiles, platelet aggregation, blood pressure, and brachial artery reactivity. Additionally, effects on markers of inflammation and blood glucose have been documented. A wide variety of grape juices, test dosages, durations, and study populations (eg, healthy adults; patients on hemodialysis; patients with hypercholesterolemia, hypertension, coronary artery disease, type 2 diabetes, metabolic syndrome; pediatric cancer survivors) have been evaluated in trials.(Blair 2014, Draijer 2015, Hyson 2015, Leifert 2008) Improved lipid profiles were observed in patients on hemodialysis after 2 weeks of grape juice supplementation.(Castilla 2006, Castilla 2008) However, in studies of healthy adults(Hollis 2009) and of patients with hypercholesterolemia,(Coimbra 2005) mild hypertension,(Draijer 2015, Park 2009) or type 2 diabetes,(Banini 2006) or of cancer survivors subjected to cardiotoxic chemotherapy,(Blair 2014) no changes in plasma lipids with 2 to 12 weeks of grape juice supplementation (one study used a grape juice extract) were observed. Platelet aggregation was reduced in some,(Keevil 2000, Pace-Asciak 1996) but not all, studies.(Draijer 2015, Hollis 2009) In studies of mild hypertension, there was no effect on ambulatory blood pressure(Draijer 2015); however, a decrease in nocturnal systolic blood pressure was observed in one study,(Dohadwala 2010) and small (6 to 7 mm Hg) decreases were found in another.(Coimbra 2005) Endothelial function in patients with metabolic syndrome,(Hashemi 2010) hypercholesterolemia,(Hollis 2009) and coronary artery disease,(Chou 2001, Stein 1999) as well as in healthy adults,(Hampton 2010) improved with grape juice supplementation. However, no benefit in vascular function occurred in pediatric cancer survivors,(Blair 2014) or in a double-blind, randomized, placebo-controlled incomplete crossover trial of 26 mildly hypertensive adults who received a grape juice extract. However, compared with placebo, a significant increase (+0.13 pg/mL) in vasoconstrictor endothelin-1 was observed with grape juice extract (P<0.05) in the study of mildly hypertensive adults.(Draijer 2015)

In a double-blind, randomized crossover study of 26 adult smokers with no evidence of chronic disease, consumption of Concord grape juice for 2 weeks significantly improved endothelial function compared with baseline, as measured by flow-mediated dilation (FMD) (P=0.02); these changes were not observed during the study's grapefruit juice phase. Juices were dosed at 7 mL/kg/day and consumed in 2 divided doses per day. Mixed model testing revealed that smoking-induced worsening of FMD and aortic stiffening was greater in men than in women and that, compared with grapefruit juice, Concord grape juice had improved both endothelial function and aortic stiffness on days 7 and 14. No changes in metabolic parameters or blood pressure were observed.(Siasos 2014) However, these measures are largely surrogate markers for cardiac morbidity and mortality, and clinical trials evaluating direct outcomes are needed.

In a randomized, controlled crossover trial conducted in pediatric cancer survivors at increased risk of premature cardiovascular disease in early adulthood because of the cardiovascular toxicity of treatment protocols, the effects of purple grape juice on vascular health were assessed during two 4-week intervention periods (purple grape juice or clear apple juice). Compared with low-polyphenol clear apple juice, dietary supplementation with 6 ounces of purple grape juice twice daily for 4 weeks did not result in significant improvements in peripheral microvascular endothelial function, biomarkers of inflammation or oxidative stress, blood pressure, lipids, glucose, or insulin. However, a significant decrease in HDL cholesterol compared with baseline was observed during the apple juice phase (median change, −5 mg/dL; P=0.001), which was significantly different from the change during the grape juice supplementation phase (median change, −1 mg/dL; P=0.04). No adverse events were reported.(Blair 2014)

Consumption of white grape juice produced from V. labrusca grapes with no added sugar or preservatives improved anthropometric parameters as well as HDL in 25 non-smoking, non-diabetic women in an uncontrolled dietary intervention study. After 30 days of consuming 7 mL/kg/day of white grape juice, statistically significant reductions from baseline were observed in mean body mass index (−0.2 kg/m2), waist circumference (−1.9 cm), and abdominal circumference (−1.8 cm; P<0.001 for each). Additionally, a significant increase of 16% in mean HDL was observed (+8.3 mg/dL; P<0.05). No other significant changes were noted in other cardiometabolic parameters including blood pressure, other lipid parameters, blood glucose, insulin, or oxidative biomarkers. The women were 50 to 67 years of age, of normal body weight (44%) or overweight (40%), and the majority (88%) were on chronic medication (ie, thyroid hormones, bisphosphonates, sex hormones, statins, antihypertensives, antidepressants, diuretics). Grape juice ranked 8th on the list as far as foods contributing to total dietary antioxidant capacity (5.06%); with mate, coffee, and tea contributing a total of 40%; and apples, oranges, bananas, and purple wine rounding out the other 7 ranked contributors.(Zuanazzi 2019)

Cognitive effects

Animal data

Rats fed purple grape juice showed improved motor function and cognition, as demonstrated in the water maze test.(Joseph 2009)

Clinical data

A small study evaluated the effects of purple grape juice 6 and 9 mL/kg/day for 12 weeks on elderly participants with nondementia memory lapse. An improvement in verbal learning and retention was demonstrated; however, no improvements in nonverbal memory or in symptoms of depression were observed.(Krikorian 2010) Subsequent systematic reviews have not identified additional data supporting use of purple grape juice for improvement in cognitive performance in patients with cognitive or memory dysfunction.(Forbes 2015, Hyson 2015) A small placebo-controlled crossover study compared the effects of a single dose of purple grape juice with the effects of white grape juice in 20 young, healthy adults. Purple grape juice demonstrated improvements in attention reaction time and increased calm but had no effect on memory performance.(Haskell-Ramsay 2017)

A small, industry-funded, double-blind, randomized, placebo-controlled, crossover study with manuscript approval from Welch Foods, Inc., investigated the effects of Concord grape juice on cognitive performance, tested using an immersive driving simulation. Healthy working mothers 40 to 50 years of age who consumed low quantities of dietary fruits and vegetables (less than 3 portions/day) and who had at least 1 child younger than 13 years consumed 355 mL/day of grape juice (777 mg total polyphenols) or an energy-, carbohydrate-, and sugar-matched placebo for 12 weeks, followed by a 4-week washout period prior to crossing over. Immediate verbal recall (P<0.05) and executive function (P<0.01) were significantly faster for grape juice relative to placebo in the study arm receiving grape juice followed by placebo. Dislike of drinking the juice (n=2) and depression (n=1) were reasons given for withdrawing from the study.(Lamport 2016)

In one study, V. vinifera extract was compared to placebo for effects on cognition and memory after 12 weeks in adults 55 to 75 years of age.(Calapai 2017) At study end, significant decreases were observed in Beck Depression Inventory and Hamilton Anxiety Rating Scale scores, and significant increases were observed in Repeatable Battery for the Assessment of Neuropsychological Status and Mini–Mental State Examination scores with the V. vinifera extract.

GU effects

Clinical data

In a double-blind, randomized, placebo-controlled trial of 113 symptomatic men at least 45 years of age, no significant effects of grape juice on lower urinary tract symptoms were identified, with the exception of maximum urine flow rates. After 3 months of Concord grape juice consumption at 240 mL/day, mean maximum uroflow rates were significantly improved compared with placebo (+1.2 vs −1.6 mL/second, respectively; P<0.01). No adverse events were noted, but other statistically significant effects were observed between groups with regard to antioxidant levels, symptom scores, erectile function, and general health scores.(Spettel 2013)

GI effects

Clinical data

A pilot study evaluated the effects of purple grape juice on chemotherapy-induced nausea and vomiting. A trend towards an effect was observed; however, the dropout rate was too high to calculate statistical significance.(Ingersoll 2010)

Histone acetylation

Clinical data

Consumption of grape juice from V. labrusca did not modulate epigenetics, specifically histone acetylation, in healthy elderly women or in patients with Parkinson disease.(Dani 2021, Oliveira 2020) In a small double-blind, randomized, placebo-controlled trial conducted in 29 older women (mean age, 70 years), 1-month consumption of 400 mL/day of grape juice did not produce any significant changes in global histone acetylation levels of H3 or H4 between groups. Additionally, the significant decrease in interleukin-6 levels observed with the physical exercise program was not affected by the addition of grape juice. Although enzymatic antioxidant biomarkers were not significantly affected by grape juice consumption, the non-enzymatic antioxidant defense system was increased (P=0.002).(Dani 2021)

Patients at least 48 years of age diagnosed with idiopathic Parkinson disease and on regular drug treatment were enrolled in a blind, randomized, controlled trial to determine the effect of grape juice (V. labrusca) consumption alone and in combination with aquatic physical exercise on global histone H4 acetylation and motor/functional outcomes. Data from the 19 patients who completed the 1 month intervention demonstrated no additional effect of grape juice consumption added to aquatic exercise. Both groups experienced significant improvements in functional capacity (P=0.001), balance (P=0.007), brain-derived neurotrophic factor levels (P=0.003), and global histone H4 acetylation (P=0.031), with no significant differences observed between groups.(Oliveira 2020)

Immune effects

Animal data

In one study, purple grape juice upregulated the immune system in animal models.(Percival 2009)

Clinical data

A study in healthy adults demonstrated increased numbers of circulating T cells and improved serum antioxidant capacity with purple grape juice over 9 weeks.(Rowe 2011)

Dosing

In a systematic review investigating the effects of grape juice on human health, grape juice was administered in dosage ranges of 4 to 18 mL/kg/day and 100 to 500 mL/day for 5 to 30 days, often in 2 divided doses.Hyson 2015

Cardiac disease/risk factors

A wide variety of test dosages have been used to evaluate effects of dietary supplementation with grape juice on various cardiovascular disease risk factors. Dosages have ranged from 4 to 18 mL/kg/day, often in divided doses (durations ranged from 2 to 8 weeks), in some studies,Chou 2001, Dohadwala 2010, Hashemi 2010, Hyson 2015, Park 2009 while other studies used grape juice dosages of 100 to 500 mL/day (durations of 2 to 12 weeks).Banini 2006, Castilla 2008, Coimbra 2005, Hampton 2010, Hollis 2009, Hyson 2015 However, efficacy of these dosages has not been proven.

Urinary tract symptoms

A 3-month intervention of 240 mL/day of grape juice was used in a clinical trial that enrolled men with lower urinary tract symptoms.Spettel 2013

Pregnancy / Lactation

Purple grape juice has GRAS status when used as food. Avoid amounts greater than those found in food because safety has not been established.

Interactions

Case reports of interactions with purple grape juice are lacking. In vitro studies demonstrate an effect on cytochrome P450 (CYP-450) 2C9 and 3A; however, no effect on flurbiprofen (suggested as a marker of warfarin) was found for CYP2C9,Greenblatt 2006 and grapes were less inhibitory than grapefruit on CYP3A activity.Kim 2006 In healthy volunteers, no influence on pharmacokinetics or pharmacodynamics of diltiazem was found,Ahmed 2008 whereas a decreased AUC and Cmax for cyclosporine were shown, suggesting a need to separate purple grape juice consumption from cyclosporine dosing by at least 2 hours.Oliveira-Freitas 2010

Adverse Reactions

Purple grape juice was generally well tolerated in clinical studies.Blair 2014, Spettel 2013, Toaldo 2015 Dislike for drinking the juice (n=2) and depression (n=1) were reported as reasons for withdrawal in one study.Lamport 2016 Case reports of immunoglobulin E–mediated allergy, including severe anaphylaxis to grapes and grape products, exist.Kalogeromitros 2005 Increases in serum-fasting insulin, possibly due to an increased carbohydrate load, have also occurred in clinical studies.Krikorian 2010, Willett 2007 Grape juice is more acidogenic than orange and pineapple juices, and regular consumption may contribute to the erosion of tooth enamel.Banan 2005, Hannig 2009 Grape juice may also have a mild laxative effect.

Toxicology

No data.

References

Disclaimer

This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

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