Effects of Concord grape juice flavor intensity and phenolic compound content on glycemia, appetite and cognitive function in adults with excess body weight: a randomized double-blind crossover trial.

Background & aims: Concord grape (Vitis lambrusca) juice (CGJ) contains a unique combination of polyphenolic compounds with diverse effects on human health. It also has an intense sensory profile that may modify food choice. Daily consumption of CGJ over 8 weeks reduced fasting blood glucose. However, the impact on 24h-postprandial glucose response from CGJ is still not clear. The purpose of this study was to assess the effect of CGJ flavor intensity and phenolic content on 24 h postprandial glucose concentrations, appetitive sensations, and cognitive function in adults with excess body weight when consumed alone or with a meal. Methods: In a randomized, double-blind, crossover design study, participants consumed three types of beverages: 100% CGJ, a polyphenol-free grape flavored drink with the same flavor essence (LP) or a polyphenol-free grape flavored drink with reduced flavor essence (LPF) either without (trial I) or with (trial II) a meal. 24 h glucose was measured through continuous glucose monitoring. Phenolic metabolite excretion was assessed in 24 h urine samples. Appetite (hunger, thirst, fullness, desire to eat, and prospective consumption) and cognitive function (alertness, energetic, strength, calmness, and relaxation) were assessed hourly through visual analog scales. Results: Thirty-four adults completed trial I and 34 adults completed trial II. When consumed with a meal, beverages with customary flavor essence (CGJ and LP) reduced hunger, desire to eat, and prospective consumption and consumption of the polyphenol-free reduced flavor essence beverage was associated with higher 24 h glucose tAUC. No consistent effects were observed for cognitive outcomes. When consumed alone, CGJ was related to lower glycemic responses by those excreting a higher concentration of the phenolic metabolite iso/ferulic-3'-O-glucuronide, but in beverages without CG phenolics and reduced flavor essence, glycemia was higher among those excreting higher concentrations of caffeic acid-O-sulfate. Conclusions: Both natural phenolics and flavor essence of CGJ may help to moderate appetite and glycemia. Clinical Trials registered at http://www.clinicaltrials.gov: NCT03409484 (trial I) and NCT03409497 (trial II).

Comparative assessment of phenolic bioaccessibility from 100% grape juice and whole grapes.

Juicing of grapes includes contact with phenolic rich seeds and skins that otherwise rely on maceration for phenolic release. To understand if 100% grape juice can provide a matrix with highly bioaccessible phenolics relative to whole fruit, differences in phenolic content and bioaccessibility from commonly consumed table, Concord (CG) and Niagara (NG) grapes and their 100% juices were compared. Phenolic contents in whole grapes and 100% juices were assayed by LC-MS prior to in vitro digestion to determine phenolic bioaccessibility. Phenolic compounds were concentrated in CG and NG seeds as flavan-3-ols (222.2-285.5 mg per 100 g fw). CG skins were rich in anthocyanins (201.4 mg per 100 g fw) and flavonols (15.5 mg per 100 g fw). Product form had a significant impact on content (p < 0.01), relative bioaccessibility, and absolute bioaccessibility (p < 0.01). CG had a higher total phenolic content (21.9-50.7 mg per 100 g fw) compared to CGJ (5.8 mg per 100 g fw), though NG (4.9-10.8 mg per 100 g fw) was similar in phenolic content to NGJ (9.4-10.8 mg per 100 g fw). Absolute bioaccessibility of total phenolics from CGJ (5.2 mg per 100 g fw) was similar to CG (2.6-9.6 mg per 100 g fw), while NGJ (5.1-5.7 mg per 100 g fw) had higher bioaccessible phenolic content than NG (0.8-1.1 mg per 100 g fw). Differences in bioaccessible content were driven by high relative bioaccessibility of anthocyanins in CGJ (86-135%) compared to CG (14-39%) as well as for flavan-3-ols and phenolic acids from CGJ/NGJ (48-101; 39-85%) compared to CG/NG (0-3; 9-67%). Comparisons between juices and table grapes followed similar trends. A greater fraction of skin and seed phenolics was extracted through juicing and made bioaccessible, making 100% grape juice and whole fruit similar in phenolic delivery to consumers.

Potential health benefits of (poly)phenols derived from fruit and 100% fruit juice.

(Poly)phenol-rich diets have been associated with reduced risk of various diseases. Coffee and tea are typically identified as dietary sources of chlorogenic acid and flavan-3-ols; however, 100% fruit juice greatly contributes to anthocyanin, flavonol, flavan-3-ols, and flavanone intake, making them complementary sources of dietary (poly)phenols. Thus, the aim of this narrative review was to provide an overview of fruit (poly)phenols and their potential health benefits. Fruit (poly)phenols have been associated with several health benefits (eg, reduced risk of cardiovascular disease and neurocognitive benefits). Although perspectives on 100% fruit juice consumption are controversial due to the perception of sugar content, growing evidence supports the role of fruit in whole and 100% juice forms to provide consumer benefits in alignment with dietary guidance. However, differences in (poly)phenol profiles and bioavailability likely exist between whole fruit and 100% fruit juice due to processing and the presence/absence of fiber. Ongoing studies are better defining similarities and differences between whole fruit and 100% fruit juice to elucidate protective mechanisms and align with processing and consumer products.

Concord and Niagara Grape Juice and Their Phenolics Modify Intestinal Glucose Transport in a Coupled in Vitro Digestion/Caco-2 Human Intestinal Model.

While the potential of dietary phenolics to mitigate glycemic response has been proposed, the translation of these effects to phenolic rich foods such as 100% grape juice (GJ) remains unclear. Initial in vitro screening of GJ phenolic extracts from American grape varieties (V. labrusca; Niagara and Concord) suggested limited inhibitory capacity for amylase and α-glucosidase (6.2%-11.5% inhibition; p < 0.05). Separately, all GJ extracts (10-100 µM total phenolics) did reduce intestinal trans-epithelial transport of deuterated glucose (d7-glu) and fructose (d7-fru) by Caco-2 monolayers in a dose-dependent fashion, with 60 min d7-glu/d7-fru transport reduced 10%-38% by GJ extracts compared to control. To expand on these findings by assessing the ability of 100% GJ to modify starch digestion and glucose transport from a model starch-rich meal, 100% Niagara and Concord GJ samples were combined with a starch rich model meal (1:1 and 1:2 wt:wt) and glucose release and transport were assessed in a coupled in vitro digestion/Caco-2 cell model. Digestive release of glucose from the starch model meal was decreased when digested in the presence of GJs (5.9%-15% relative to sugar matched control). Furthermore, transport of d7-glu was reduced 10%-38% by digesta containing bioaccessible phenolics from Concord and Niagara GJ compared to control. These data suggest that phenolics present in 100% GJ may alter absorption of monosaccharides naturally present in 100% GJ and may potentially alter glycemic response if consumed with a starch rich meal.

Concord grape juice, cognitive function, and driving performance: a 12-wk, placebo-controlled, randomized crossover trial in mothers of preteen children.

BACKGROUND: Daily consumption of Concord grape juice (CGJ) over 3-4 mo has been shown to improve memory function in adults with mild cognitive impairment and reduce blood pressure in hypertensive adults. These benefits likely result from the high concentration of polyphenols in CGJ. Increased stress can impair cognitive function and elevate blood pressure. Thus, we examined the potential beneficial effect of CGJ in individuals with somewhat stressful and demanding lifestyles. OBJECTIVE: We sought to examine the effects of the daily consumption of CGJ for 12 wk on cognitive function, driving performance, and blood pressure in healthy, middle-aged working mothers. DESIGN: Twenty-five healthy mothers (aged 40-50 y) of preteen children who were employed for ≥30 h/wk consumed 12 ounces (355 mL) of either CGJ (containing 777 mg total polyphenols) or an energy-, taste-, and appearance-matched placebo daily for 12 wk according to a randomized crossover design with a 4-wk washout. Verbal and spatial memory, executive function, attention, blood pressure, and mood were assessed at baseline and at 6 and 12 wk. Immediately after the cognitive battery, a subsample of 17 women completed a driving performance assessment at the University of Leeds Driving Simulator. The 25-min driving task required participants to match the speed and direction of a lead vehicle. RESULTS: Significant improvements in immediate spatial memory and driving performance were observed after CGJ relative to placebo. There was evidence of an enduring effect of CGJ such that participants who received CGJ in arm 1 maintained better performance in the placebo arm. CONCLUSIONS: Cognitive benefits associated with the long-term consumption of flavonoid-rich grape juice are not exclusive to adults with mild cognitive impairment. Moreover, these cognitive benefits are apparent in complex everyday tasks such as driving. Effects may persist beyond the cessation of flavonoid consumption, and future studies should carefully consider the length of washout within crossover designs. This trial was registered at clinicaltrials.gov as NCT01411631.

Effect of grape and other berries on cardiovascular health.

Cardiovascular disease is a leading cause of death globally. Many cardiovascular risk factors can be modified through lifestyle modification, including dietary patterns that emphasize daily consumption of a variety of fruits and vegetables. Recent observational and clinical studies suggest that flavonoids, especially those abundant in grapes and other berries, may be associated with health benefits, particularly cardiovascular benefits. Human clinical data support cardioprotective benefits of grapes through inhibition of platelet aggregation, decreased low-density lipoprotein (LDL) oxidation, reduction in oxidative stress and improvements in endothelial function. Emerging evidence suggests that grapes may also have a favorable effect on blood lipids, decrease inflammation and reduce blood pressure in certain populations. Studies to date have shown that berries can have a beneficial effect on reducing LDL oxidation. Limited data suggest that berries may have a favorable effect on endothelial health and blood pressure. This review summarizes the current literature on human clinical studies examining the cardioprotective benefits of grapes and berries. Collectively, these data support the recommendation to incorporate products made with grapes and other berries into a heart-healthy diet.

Improved diet quality and increased nutrient intakes associated with grape product consumption by U.S. children and adults: National Health and Nutrition Examination Survey 2003 to 2008.

Fruit contributes to dietary nutrient density and consumption of fruit in several forms (whole, dried, or 100% juice) has been reported to be associated with a healthier dietary pattern. The goal of this study was to examine the associations of the consumption of grapes (including fresh grapes, raisins, and 100% grape juice) with diet quality and food group/nutrient intake. A secondary analysis of Natl. Health and Nutrition Examination Survey (NHANES) 2003 to 2008 data was conducted to compare grape consumers (GC) with nongrape consumers (NGC) among children aged 2 to 19 y (n = 9622) and adults 20+ y (n = 12251). GC were defined as those who mentioned the consumption of fresh grapes, raisins, or 100% grape juice during 1 or both 24-h recall interviews. Compared to NGC, GC had higher Healthy Eating Index 2005 (HEI-2005) scores and higher intakes of total and whole fruit along with lower intakes of solid fat, added sugars, and calories from solid fats, alcohol, and added sugars (SoFAAS). Among adults, GC also had higher intakes than NGC of total and dark green/orange vegetables. Among both age groups, GC had higher intake than NGC of several key nutrients including dietary fiber, vitamin A, vitamin C, calcium, magnesium, and potassium. Consumption of grape products is associated with a healthier dietary pattern and higher intake of key nutrients by both children and adults.

Colonic catabolism of dietary phenolic and polyphenolic compounds from Concord grape juice.

After acute ingestion of 350 ml of Concord grape juice, containing 528 µmol of (poly)phenolic compounds, by healthy volunteers, a wide array of phase I and II metabolites were detected in the circulation and excreted in urine. Ingestion of the juice by ileostomists resulted in 40% of compounds being recovered intact in ileal effluent. The current study investigated the fate of these undigested (poly)phenolic compounds on reaching the colon. This was achieved through incubation of the juice using an in vitro model of colonic fermentation and through quantification of catabolites produced after colonic degradation and their subsequent absorption prior to urinary excretion by healthy subjects and ileostomy volunteers. A total of 16 aromatic and phenolic compounds derived from colonic metabolism of Concord grape juice (poly)phenolic compounds were identified by GC-MS in the faecal incubation samples. Thirteen urinary phenolic acids and aromatic compounds were excreted in significantly increased amounts after intake of the juice by healthy volunteers, whereas only two of these compounds were excreted in elevated amounts by ileostomists. The production of phenolic acids and aromatic compounds by colonic catabolism contributed to the bioavailability of Concord grape (poly)phenolic compounds to a much greater extent than phase I and II metabolites originating from absorption in the upper gastrointestinal tract. Catabolic pathways are proposed, highlighting the impact of colonic microbiota and subsequent phase II metabolism prior to excretion of phenolic compounds derived from (poly)phenolic compounds in Concord grape juice, which pass from the small to the large intestine.

Concord grape juice supplementation and neurocognitive function in human aging.

Polyphenol compounds found in berry fruits, in particular flavonoids, have been associated with health benefits including improvement in cognition and neuronal function with aging. Concord grape juice contains polyphenols, including anthocyanins and flavanols, and previous research has shown improvement in a number of human health conditions with grape juice supplementation. In the current study, older adult subjects with mild cognitive impairment consumed Concord grape juice or placebo for 16 weeks and were administered assessments of memory function and brain activation pre- and postintervention. Participants who consumed grape juice showed reduced semantic interference on memory tasks. Relatively greater activation in anterior and posterior regions of the right hemisphere was also observed with functional magnetic resonance imaging in the grape juice treated subjects. These findings provide further evidence that Concord grape juice can enhance neurocognitive function in older adults with mild memory decline.

Gastrointestinal stability and bioavailability of (poly)phenolic compounds following ingestion of Concord grape juice by humans.

The in vitro gastrointestinal stability of (poly)phenolic compounds in Concord grape juice was compared with recoveries in ileal fluid after the ingestion of the juice by ileostomists. Recoveries in ileal fluid indicated that 67% of hydroxycinnamate tartarate esters, and smaller percentages of the intake of other (poly)phenolic compounds, pass from the small intestine to the colon. The juice was also ingested by healthy subjects with an intact functioning colon. Peak plasma concentrations (C(max) ) ranged from 1.0 nmol/L for petunidin-3-O-glucoside to 355 nmol/L for dihydrocoumaric acid. Urinary excretion, as an indicator of bioavailability, varied from 0.26% for total anthocyanins to 24% for metabolites of hydroxycinnamate tartarate esters. The C(max) times of the anthocyanins indicated that their low level absorption occurred in the small intestine in contrast to hydroxycinnamate metabolites which were absorbed in both the small and the large intestine where the colonic microflora appeared responsible for hydrogenation of the hydroxycinnamate side chain. The bioavailability of the complex mixture of (poly)phenolic compounds in Concord grape juice, was very similar to that observed in previous studies when compounds were either fed individually or as major components in products containing a restricted spectrum of (poly)phenolic compounds.

Survey of polyphenol constituents in grapes and grape-derived products.

A rapid and comprehensive qualitative method has been developed to characterize the different classes of polyphenols, such as anthocyanins, flavonols, phenolic acids, and flavanols/proanthocyanidins, in grape products. The detection was achieved by two runs with the same LC gradient in different MS ionization modes and mobile phase modifiers (positive ionization mode and 0.4% trifluoroacetic acid for anthocyanins and flavonols; negative ionization mode and 0.1% formic acid for phenolic acids and flavanols). From an analysis of the MS and UV data and in comparison with the authenticated standards, a total of 53 compounds were identified, including 33 anthocyanins, 12 flavonols, 4 phenolic acids, and 4 flavanols/proanthocyanidins. With the method developed, a survey was then conducted to qualitatively assess the composition of polyphenols among 29 different grape products including original grape, grape juice, grape wine, and grape-derived dietary supplements, and their chemical profiles were systematically compared. This method provided a comprehensive qualitative insight into the composition of polyphenols in grape-derived products.

Identification of (poly)phenolic compounds in concord grape juice and their metabolites in human plasma and urine after juice consumption.

Analysis of Concord grape juice by HPLC with ESI-MS(n), PDA, and fluorescence detection resulted in the identification and quantification of 60 flavonoids and related phenolic compounds, which were present at an overall concentration of 1508 ± 31 µmol/L. A total of 25 anthocyanins were detected, which were mono- and di-O-glucosides, O-acetylglucosides, O-p-coumaroyl-O-diglucosides, and O-p-coumaroylglucosides of delphinidin, cyanidin, petunidin, peonidin, and malvidin. The anthocyanins represented 46% of the total phenolic content of the juice (680 µmol/L). Tartaric esters of hydroxycinnamic acids, namely, trans-caftaric and trans-coutaric acids, and to a lesser extent trans-fertaric acid accounted for 29% of the phenolic content, with a total concentration of 444 µmol/L, of which 85% comprised trans-caftaric acid. Free hydroxycinnamic acids were also quantified but contributed to <1% of the total phenolic content (8.4 µmol/L). The other groups of polyphenolic compounds present in the juice, accounting for 24% of the total, comprised monomeric and oligomeric units of (epi)catechin and (epi)gallocatechin (248 µmol/L), flavonols (76 µmol/L), gallic acid (51 µmol/L), and trans-resveratrol (1.5 µmol/L). The bioavailability of the (poly)phenolic compounds in 350 mL of juice was investigated following acute intake by healthy volunteers. Plasma and urine were collected over 0-24 h and analyzed for parent compounds and metabolites. In total, 41 compounds, principally metabolites, were identified.