Grape Juice

Generic name: Vitis Labrusca L., Vitis Rotundifolia Michx., Vitis Vinifera L.
Brand names: American Bunch Grapes (V. Labrusca), European Or "Old World" Grapes (V. Vinifera), Muscadine Grapes (V. Rotundifolia)

Usage of Grape Juice

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)

Grape Juice side effects

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.

Before taking Grape Juice

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

How to use Grape Juice

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

Warnings

No data.

What other drugs will affect Grape Juice

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

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