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Inter-Individual Variability in Insulin Response after Grape Pomace Supplementation in Subjects at High Cardiometabolic Risk: Role of Microbiota and miRNA.
Ramos-Romero, S, Léniz, A, Martínez-Maqueda, D, Amézqueta, S, Fernández-Quintela, A, Hereu, M, Torres, JL, Portillo, MP, Pérez-Jiménez, J
Molecular nutrition & food research. 2021;(2):e2000113
Abstract
SCOPE Dietary polyphenols have shown promising effects in mechanistic and preclinical studies on the regulation of cardiometabolic alterations. Nevertheless, clinical trials have provided contradictory results, with high inter-individual variability. This study explores the role of gut microbiota and microRNAs (miRNAs) as factors contributing to the inter-individual variability in polyphenol response. METHODS AND RESULTS 49 subjects with at least two factors of metabolic syndrome are divided between responders (n = 23) or non-responders (n = 26), depending on the variation rate in fasting insulin after grape pomace supplementation (6 weeks). The populations of selected fecal bacteria are estimated from fecal deoxyribonucleic acid (DNA) by quantitative real-time polymerase chain reaction (qPCR), while the microbial-derived short-chain fatty acids (SCFAs) are measured in fecal samples by gas chromatography. MicroRNAs are analyzed on a representative sample, followed by targeted miRNA analysis. Responder subjects show significantly lower (p < 0.05) Prevotella and Firmicutes levels, and increased (p < 0.05) miR-222 levels. CONCLUSION After evaluating the selected substrates for Prevotella and target genes of miR-222, these variations suggest that responders are those subjects exhibiting impaired glycaemic control. This study shows that fecal microbiota and miRNA expression may be related to inter-individual variability in clinical trials with polyphenols.
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Grape pomace polyphenols improve insulin response to a standard meal in healthy individuals: A pilot study.
Costabile, G, Vitale, M, Luongo, D, Naviglio, D, Vetrani, C, Ciciola, P, Tura, A, Castello, F, Mena, P, Del Rio, D, et al
Clinical nutrition (Edinburgh, Scotland). 2019;(6):2727-2734
Abstract
BACKGROUND & AIMS Dietary polyphenols have beneficial effects on glucose/lipid metabolism in subjects at high risk to develop type 2 diabetes; however, the underlying mechanisms are not clear. We aimed to evaluate: 1) the acute effects of the consumption of a drink rich in polyphenols from red grape pomace (RGPD) on glucose/insulin and triglyceride responses to a standard meal in healthy individuals, and, 2) the relationship between plasma levels of phenolic metabolites and metabolic parameters. METHODS Twelve healthy men, aged 20-40 years participated in a randomized, controlled study according to a cross-over design. After a 3-day low-polyphenol diet, all participants consumed, on two different days and separated by a one week interval, after an overnight fast, a drink rich in polyphenols (1.562 g gallic acid equivalents (GAE)) or a control drink (CD, no polyphenols), followed after 3 h by a standard meal (960 kcal, 18% protein, 30% fat, 52% CHO). Blood samples were taken at fasting, 3 h after the drink, over 5 h after the standard meal and at fasting on the next day to measure plasma concentrations of glucose, insulin, triglyceride and phenolic metabolites. RESULTS Glycemic and triglyceride post-meal responses were similar after both the RGPD and the control drink. In contrast, postprandial insulin incremental area (iAUC0-5h) was 31% lower (p < 0.05), insulin secretion index was 18% lower (p < 0.016) and insulin sensitivity (SI) index was 36% higher (p = 0.037) after the RGPD compared to CD. Among phenolic metabolites, gallic acid correlated inversely with the insulin response (r = -0.604; p = 0.032) and positively with the SI index (r = 0.588, p = 0.037). CONCLUSIONS RGPD consumption acutely reduced postprandial insulin levels and improved insulin sensitivity. This effect could be likely related to the increase in gallic acid levels. This drink, added to usual diet, could contribute to increase the daily intake of polyphenols, with potential health benefits. CLINICALTRIALS. GOV IDENTIFIER NCT02865278.
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Polyphenols From Grape and Blueberry Improve Episodic Memory in Healthy Elderly with Lower Level of Memory Performance: A Bicentric Double-Blind, Randomized, Placebo-Controlled Clinical Study.
Bensalem, J, Dudonné, S, Etchamendy, N, Pellay, H, Amadieu, C, Gaudout, D, Dubreuil, S, Paradis, ME, Pomerleau, S, Capuron, L, et al
The journals of gerontology. Series A, Biological sciences and medical sciences. 2019;(7):996-1007
Abstract
Polyphenols are promising nutritional bioactives exhibiting beneficial effect on age-related cognitive decline. This study evaluated the effect of a polyphenol-rich extract from grape and blueberry (PEGB) on memory of healthy elderly subjects (60-70 years-old). A bicentric, randomized, double-blind, placebo-controlled trial was conducted with 215 volunteers receiving 600 mg/day of PEGB (containing 258 mg flavonoids) or a placebo for 6 months. The primary outcome was the CANTAB Paired Associate Learning (PAL), a visuospatial learning and episodic memory test. Secondary outcomes included verbal episodic and recognition memory (VRM) and working memory (SSP). There was no significant effect of PEGB on the PAL on the whole cohort. Yet, PEGB supplementation improved VRM-free recall. Stratifying the cohort in quartiles based on PAL at baseline revealed a subgroup with advanced cognitive decline (decliners) who responded positively to the PEGB. In this group, PEGB consumption was also associated with a better VRM-delayed recognition. In addition to a lower polyphenol consumption, the urine metabolomic profile of decliners revealed that they excreted more metabolites. Urinary concentrations of specific flavan-3-ols metabolites were associated, at the end of the intervention, with the memory improvements. Our study demonstrates that PEGB improves age-related episodic memory decline in individuals with the highest cognitive impairments.
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The Oral Bioavailability of Trans-Resveratrol from a Grapevine-Shoot Extract in Healthy Humans is Significantly Increased by Micellar Solubilization.
Calvo-Castro, LA, Schiborr, C, David, F, Ehrt, H, Voggel, J, Sus, N, Behnam, D, Bosy-Westphal, A, Frank, J
Molecular nutrition & food research. 2018;(9):e1701057
Abstract
SCOPE Grapevine-shoot extract Vineatrol30 contains abundant resveratrol monomers and oligomers with health-promoting potential. However, the oral bioavailability of these compounds in humans is low (˂1-2%). The aim of this study was to improve the oral bioavailability of resveratrol from vineatrol by micellar solubilization. METHODS AND RESULTS Twelve healthy volunteers (six women, six men) randomly ingested a single dose of 500 mg vineatrol (30 mg trans-resveratrol, 75 mg trans-ε-viniferin) as native powder or liquid micelles. Plasma and urine were collected at baseline and over 24 h after intake. Resveratrol and viniferin were analyzed by HPLC. The area under the plasma concentration-time curve (AUC) and mean maximum plasma trans-resveratrol concentrations were 5.0-fold and 10.6-fold higher, respectively, after micellar supplementation relative to the native powder. However, no detectable amounts of trans-ε-viniferin were found in either plasma or urine. The transepithelial permeability of trans-resveratrol and trans-ε-viniferin across differentiated Caco-2 monolayers was consistent to the absorbed fractions in vivo. CONCLUSION The oral bioavailability of trans-resveratrol from the grapevine-shoot extract Vineatrol30 was significantly increased using a liquid micellar formulation, without any treatment-related adverse effects, making it a suitable system for improved supplementation of trans-resveratrol.
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Effects of grape consumption on biomarkers of inflammation, endothelial function, and PBMC gene expression in obese subjects.
Bardagjy, AS, Hu, Q, Giebler, KA, Ford, A, Steinberg, FM
Archives of biochemistry and biophysics. 2018;:145-152
Abstract
This study investigated effects of grape consumption on biomarkers of cardiovascular health in obese participants in both postprandial and chronic settings. Twenty obese adults participated in this randomized, placebo controlled, double-blinded crossover trial. Participants were randomized to consume 60 g freeze-dried polyphenol-rich whole grape powder (GP) or placebo (PBO) followed by high fat high carbohydrate (HFHC) meal challenge. Following acute challenge, participants consumed their respective treatment daily for 4 weeks to determine effects of chronic consumption. Consumption of GP with HFHC meal significantly increased nuclear factor (erythroid-derived 2)-like 2 (NRF2) expression in peripheral blood mononuclear cells (PBMC) at 3 h (p < 0.05) and decreased plasma endothelin-1 (ET-1) concentration at 5 h (p < 0.05) after meal challenge compared with PBO. Following 4 weeks of daily GP consumption, soluble vascular cell adhesion molecule 1 (sVCAM-1) plasma concentration increased compared with PBO (p < 0.05), however baseline values differed between treatments. In conclusion, GP consumption resulted in decreased vasoconstrictor ET-1 concentration and increased gene expression related to oxidative stress defense following HFHC meal. Except for increase in sVCAM-1 concentration, 4 weeks of chronic GP consumption had little effect on cardiovascular biomarkers measured in this study. This trial was registered: clinicaltrials.gov NCT01674231.
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Examining the impact of grape consumption on brain metabolism and cognitive function in patients with mild decline in cognition: A double-blinded placebo controlled pilot study.
Lee, J, Torosyan, N, Silverman, DH
Experimental gerontology. 2017;(Pt A):121-128
Abstract
BACKGROUND Natural compounds in grapes such as resveratrol are known for their antioxidant and anti-inflammatory properties. Some studies have shown a potential role for grapes or wine in slowing cognitive decline and other effects of aging. However, well-controlled experimental data obtained in human subjects are still in need of further development. Here we aimed to systematically assess effects of grapes on regional cerebral metabolism. METHODS Ten subjects with mild decline in cognition (mean, 72.2±4.7years; 50% female) were included in this analysis. Participants were randomized into an active grape formulation arm or a placebo arm which consumed a formulation free of polyphenols for six months. Cognitive performance was measured through neuropsychological assessments performed at baseline and 6months after initiation of therapy. Changes in brain metabolism occurring with each therapy regimen were assessed by brain PET scans with the radiotracer [F-18] fluorodeoxyglucose (FDG), obtained during initial evaluation and 6months later. Standardized volumes of interest (sVOI) and statistical parametric mapping (SPM) methods were applied to FDG-PET scans to identify significant regional cerebral metabolic changes. RESULTS In contrast to participants taking the active grape formulation, who displayed no significant decline in metabolism, the placebo arm underwent significant metabolic decline in sVOI's of the right posterior cingulate cortex (p=0.01), and left superior posterolateral temporal cortex (p=0.04). SPM analyses also found significant declines in the placebo group, particularly in left prefrontal, cingulate, and left superior posterolateral temporal cortex (p<0.01) with stable brain metabolism in the active formulation arm. No significant differences were seen in scores on the neuropsychological battery of tests between the two groups. However, metabolism in right superior parietal cortex and left inferior anterior temporal cortex was correlated with improvements in attention/working memory, as measured with WAIS-III Digital Span within the active formulation group (r=-0.69, p=0.04). CONCLUSIONS The placebo arm had declines in regions of the brain known to be significantly affected in the early stages of Alzheimer's disease, while the active formulation group was spared such decline. This suggests a protective effect of grapes against early pathologic metabolic decline.
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Cognitive and mood improvements following acute supplementation with purple grape juice in healthy young adults.
Haskell-Ramsay, CF, Stuart, RC, Okello, EJ, Watson, AW
European journal of nutrition. 2017;(8):2621-2631
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Abstract
PURPOSE Berry-derived phenolic compounds found in grapes have been associated with a number of health benefits, including the augmentation of human brain function and cognition. Previous intervention studies of Concord grape juice have demonstrated improvement to memory and driving ability following 3- to 4-month supplementation in middle-aged and older adults. However, no studies to date have demonstrated acute cognitive benefits of grape juice, and investigation of these effects in young adults is lacking. METHODS This randomised, placebo-controlled, double-blind, counterbalanced-crossover study, assessed the effects of 230 ml purple grape juice or sugar-matched control in 20 healthy young adults. Computerised measures of episodic memory, working memory, attention and mood were completed at baseline and following a 20-min absorption period. RESULTS Purple grape juice significantly improved reaction time on a composite attention measure (p = 0.047) and increased calm ratings (p = 0.046) when compared to placebo. Order effects also indicated an enduring positive effect on pre-dose memory reaction time (p = 0.018) and post-dose calm ratings (p = 0.019) when purple grape was consumed first. CONCLUSIONS These findings in a small sample of healthy young adults suggest that purple grape juice can acutely enhance aspects of cognition and mood. No significant effects of juice were observed on memory measures, suggesting that these may be less susceptible to manipulation following acute supplementation in healthy young adults. Potential mechanisms underlying these effects include modulation of cerebral blood flow, glucoregulation and inhibition of monoamine oxidase activity, all of which require further exploration.
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White Grape Juice Elicits a Lower Breath Hydrogen Response Compared with Apple Juice in Healthy Human Subjects: A Randomized Controlled Trial.
Erickson, J, Wang, Q, Slavin, J
Journal of the Academy of Nutrition and Dietetics. 2017;(6):908-913
Abstract
BACKGROUND Diets low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPS) are used to manage symptoms in individuals with irritable bowel syndrome. Although effective at reducing symptoms, the diet can be complex and restrictive. In addition, there are still large gaps in the literature and many foods with unclear effects in the gastrointestinal (GI) tract, like fruit juice. Although many fruits are allowable on a low-FODMAP diet, consumption of all fruit juice is generally cautioned due to the large fructose load contained in juice, regardless of the glucose concentration. Very little research exists regarding the importance of limiting fructose load during a low-FODMAP diet; therefore, individuals following a low-FODMAP diet may be unnecessarily restricting their diets. OBJECTIVE To determine whether there is a difference in GI tolerance between juice from a high-FODMAP fruit (apple juice) and juice from a low-FODMAP fruit (white grape juice) in healthy human subjects. The goal is to provide insight into the role of juice in a low-FODMAP diet. METHODS A double-blind, randomized, controlled crossover study was conducted with 40 healthy adults. Fasted subjects consumed 12 oz of either apple juice or white grape juice. Breath hydrogen measures were taken at baseline, 1, 2, and 3 hours. Subjective GI tolerance surveys were completed at the same time intervals and at 12 and 24 hours. Breath hydrogen and GI symptoms were assessed with area under the curve analysis. Significance was determined with a two-sided t test with a P value <0.05. RESULTS Consumption of apple juice resulted in a greater mean breath hydrogen area under the curve at 23.3 ppm/hour (95% CI 13.0 to 33.6) compared with white grape juice at 5.8 ppm/hour (95% CI -4.6 to 16.1) (P<0.001). No differences in reported GI symptoms were seen between treatments. CONCLUSIONS Both juices were well tolerated and neither produced any severe symptoms in healthy adults. White grape juice consumption resulted in only a small rise in breath hydrogen, which may suggest excluding foods only because of the high fructose load could be unnecessarily restrictive. The results of this study suggest that the fructose-to-glucose ratio is likely more important than the total fructose load of the food when considering the acceptability of a food on a low-FODMAP diet. More research is needed in individuals with irritable bowel syndrome to determine whether white grape juice and other juices from low-FODMAP fruits could be additional beverage options for individuals following a low-FODMAP diet.
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Effects of proanthocyanidin on oxidative stress biomarkers and adipokines in army cadets: a placebo-controlled, double-blind study.
Gonçalves, MC, Passos, MC, de Oliveira, CF, Daleprane, JB, Koury, JC
European journal of nutrition. 2017;(2):893-900
Abstract
PURPOSE The relatively recent advent of polyphenol supplement for exercise studies has been tested in a variety of forms and doses. However, the dose-response on adipokines and oxidative stress biomarker effect remains unknown. The aim of the present study was to assess the effect of intense, long-duration (48-h) exercise, and a single dose of proanthocyanidin, on plasma leptin, adiponectin, and electronegative low-density lipoprotein (LDL(-)) concentrations. METHODS Fifty-four healthy male army cadets (22 ± 2 years) participated in a double-blind, randomized, placebo-controlled study and were distributed between control (CG; n = 27) and supplemented groups (SG; n = 27). Immediately before the start of the exercise, both CG and SG groups received a capsule containing starch (200 mg) or proanthocyanidin (dry Vitis vinifera extract, 200 mg), respectively. Following a 12-h fasting period, the plasma adiponectin, leptin, and LDL(-) concentrations were measured prior to the start of the exercise after 24 and 48 h of military training, and after 24 h of rest. The effects of the proanthocyanidin (supplement), exercise (time), and their interaction were investigated using factorial two-way ANOVA. RESULTS Plasma leptin concentration was only influenced by exercise (p = 0.001). Plasma adiponectin concentration was influenced by exercise (p = 0.037), and by the exercise x supplement interaction (p = 0.033). LDL(-) was influenced by the supplement (p = 0.001), exercise (p = 0.001), and their interaction (p = 0.001). CONCLUSIONS A single dose of proanthocyanidin (200 mg) was able to reduce LDL(-) concentration and increase plasma adiponectin concentration after 24 h of rest in SG group, indicating its potential protective action.
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Identification of phenolic metabolites in human urine after the intake of a functional food made from grape extract by a high resolution LTQ-Orbitrap-MS approach.
Sasot, G, Martínez-Huélamo, M, Vallverdú-Queralt, A, Mercader-Martí, M, Estruch, R, Lamuela-Raventós, RM
Food research international (Ottawa, Ont.). 2017;(Pt 3):435-444
Abstract
Grape pomace (GP) is known to be a rich source of polyphenols with biological activity which may be used as functional ingredients for the development of new health-promoting products. Numerous studies have reported that bioactive compounds may act through multiple mechanisms. In order to verify the oral absorption and metabolism of grape polyphenols, we performed a prospective, randomised and cross-over acute study in 12 volunteers with two interventions: 500mL of a functional beverage enriched with 200mL of GP and 500mL of a control beverage without GP. In this work, liquid chromatography coupled with an electrospray ionization hybrid linear ion trap quadrupole-Orbitrap-mass spectrometry (LC/ESI-LTQ-Orbitrap-MS) technique has been used to accurately identify phenolics in GP and human urine. In GP, 41 phenolic compounds were identified mainly procyanidins, phenolic acids and flavonols, and in human urine over 70 metabolites of phenolic compounds including microbiota metabolites, glucuronides and sulfate derivatives were detected. Overall, high resolution mass spectrometry (HR-MS) enhances the identification of a large variety of polyphenols and their metabolites with great mass accuracies for all molecular ions.