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Chardonnay Marc as a New Model for Upcycled Co-products in the Food Industry: Concentration of Diverse Natural Products Chemistry for Consumer Health and Sensory Benefits
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Chardonnay Marc as a New Model for Upcycled Co-products in the Food Industry: Concentration of Diverse Natural Products Chemistry for Consumer Health and Sensory Benefits
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Journal of Agricultural and Food Chemistry

Cite this: J. Agric. Food Chem. 2022, 70, 48, 15007–15027
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https://doi.org/10.1021/acs.jafc.2c04519
Published November 21, 2022

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Abstract

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Research continues to provide compelling insights into potential health benefits associated with diets rich in plant-based natural products (PBNPs). Coupled with evidence from dietary intervention trials, dietary recommendations increasingly include higher intakes of PBNPs. In addition to health benefits, PBNPs can drive flavor and sensory perceptions in foods and beverages. Chardonnay marc (pomace) is a byproduct of winemaking obtained after fruit pressing that has not undergone fermentation. Recent research has revealed that PBNP diversity within Chardonnay marc has potential relevance to human health and desirable sensory attributes in food and beverage products. This review explores the potential of Chardonnay marc as a valuable new PBNP ingredient in the food system by combining health, sensory, and environmental sustainability benefits that serves as a model for development of future ingredients within a sustainable circular bioeconomy. This includes a discussion on the potential role of computational methods, including artificial intelligence (AI), in accelerating research and development required to discover and commercialize this new source of PBNPs.

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Introduction

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The past few decades have seen advances in science and technology enabling the systematic study of plant-based natural products (PBNPs) and their potential bioactivity in humans. This includes greater understanding of PBNPs not classified as essential nutrients, yet having considerable potential for impact on human health. Research on PBNPs encompassing broad classifications, such as the flavonoids, phenolic acids, and carotenoids, has yielded extensive insights into potential health benefits associated with diets rich in certain plant-based ingredients. In this context, epidemiological research has raised awareness of these potential benefits, while also adding phrases such as “French Paradox” and “Mediterranean Diet” to the lexicon of public health. Coupled with learnings from dietary intervention trials, the totality of this data has led to dietary recommendations that include dietary patterns with higher intakes of PBNPs. (1,2) Dietary patterns such as the Mediterranean diet and Dietary Approaches to Stop Hypertension (DASH) include high intakes of plant-based foods providing a diverse array of PBNPs, including mono- and polyunsaturated fatty acids, essential vitamins and minerals, amino acids, fiber, and phenolics. (2,3) Building on this foundation, recent data from the landmark COcoa Supplement and Multivitamin Outcomes Study (COSMOS) trial demonstrated that the daily intake of a specific class of PBNPs, in this case monomeric and polymeric flavanols from cocoa, by older individuals reduces risk for cardiovascular morbidity and mortality. (4) COSMOS demonstrates the potential for precision nutrition strategies to improve public health via dietary intake of specified PBNPs. To realize the full potential for public health benefits from such an approach, there is a need for data on the health impacts of specific PBNP compounds and classes throughout the lifespan. Importantly, for these nutrition approaches to have maximum impact, a more comprehensive understanding of food composition as it pertains to PBNPs in terms of both content and strategies for the preservation of bioactivity during processing and manufacturing of food will help aid in the identification of new product and ingredient opportunities.
In addition to health, PBNPs often drive flavor and sensory perceptions in foods and beverages. (5,6) The commercial relevance of these sensory attributes (e.g., taste, smell, and texture) has driven advances regarding the isolation and characterization of PBNPs, while also adding enormously to the general library of known compounds occurring in nature. (7) In contrast, relatively high concentrations of PBNPs can lend potentially negative sensory attributes with severe product application limitations. (8) Attributes that include astringency and bitterness may prevent broader implementation of these PBNP ingredients toward health and food applications. This is a potential limitation given their agricultural origin and the opportunity to upcycle byproducts from these materials into nutrient dense ingredients. There is increasing interest to reduce food waste and loss on a global basis for the achievement of long-term environmental sustainability, as well as food and health security. (9) Therefore, food waste streams represent an opportunity to reincorporate PBNPs back into the food system. (7)
Chardonnay marc (or pomace) is currently an underutilized byproduct of Chardonnay winemaking, consisting of seeds, stems, and skins obtained after pressing of fruit that has not undergone fermentation. The 2021 California wine crush alone generated 121,600 tons of Chardonnay wine grape marc derived from more than 3.8 million tons of wine grapes on a fresh weight basis at an average price of $975 per ton. (10) As a byproduct of wine production, there is potential interest for Chardonnay marc as a co-product or a desirable secondary product, similar to that of whey as a co-product for cheese making, particularly given the economic impact of such a waste stream to the producer. Recent research into the natural products chemistry of Chardonnay marc has revealed additional diversity of bioactive compounds potentially relevant for human health, as well as desirable sensory attributes appropriate for the development of new foods and beverages. Given the scale of this industrial sector, converting this underutilized Chardonnay marc byproduct into a valuable ingredient for use in food and beverage products represents an extraordinary opportunity for creating a sustainable circular bioeconomy within the winemaking sector. In this perspective, we examine recent advances in the characterization of natural products in Chardonnay marc, along with the potential of Chardonnay marc PBNPs to improve human health, as well as sensory characteristics of food and beverage products. We highlight the opportunity this combination of attributes enables in terms of scaling its use, with a corresponding contribution to environmental sustainability. In addition, we discuss an early application of predictive analytics of Chardonnay marc PBNPs, and the role data science can play in the acceleration of research and development of PBNP ingredients into a healthier and more sustainable food system.

Chardonnay Marc: An Underutilized Source of PBNPs

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Chardonnay originates from the famed Burgundy region of France during the Middle Ages near a village of the same name (Latin for “a place of thistles”) in Maĉon. (11) Recent genotyping places its parentage from Pinot noir and Gouais blanc (also known as Heunisch Weiss, Rebula Stara, and Belina Starohrvatska) with additional analyses suggesting a shared parentage between these two varietals. (12−15) Historically considered a poor variety, planted by peasants, efforts were made to ban Gouais blanc. (16) What attributes Gouais blanc passed on to its well-known prodigy are currently unknown. In the United States, California is the largest producer of wine, with Chardonnay as its top-planted grape. Chardonnay was present in California by the late 1880s, but as the end of prohibition in 1933, had a limited presence in the state. Viticulturist Dr. Harold P. Olmo from the University of California, Davis, and USDA ARS plant pathologist Dr. Austin Goheen are credited with the development of virus-tested clones that produced higher yields in a variety of California’s climate zones. Their work allowed for an increase in Chardonnay acreage from 986 acres in 1968 to over 7000 acres by the mid-1970s; noteworthy as by 1976 a 1973 vintage of Chateau Montelena, a California produced Chardonnay, from Napa Valley, outperformed some of France’s best in a blind test tasting in Paris. (11) Chardonnay is predominately grown in the cooler coastal regions and is the largest in tonnage of wine grapes crushed in California, representing 16.0% of the wine grapes crushed in 2021 at approximately 619,000 tons. (10)
The winemaker dictates the harvesting of wine grapes as they pursue the optimization of desired sensory attributes. Production of white wine involves pressing the must after crushing of the fruit in order to separate the juice for fermentation into wine. The remaining solids, known as marc or pomace, contain seeds, stems, pulp, and skins. Depending on the varietal, marc may account for 10–20% (w/w) of the grapes, estimated as 1 kg of marc generated for every 6 L of wine produced. (17) Chardonnay marc is a notably underutilized byproduct in this industry. The production scale of this material has driven considerable interest in upcycling of the marc, including applications relevant to agriculture, bioenergy, and extraction of industrial value added products such as enzymes and biopolymers. (18)
In general, new environmental policies and strategies are being developed and implemented to drive more sustainable byproduct management in the food and agriculture sector; however, the wine industry still relies heavily on traditional composting and livestock feed, thus yielding limited value creation to the producer in terms of financial returns. New approaches to upcycling of wine grape marc could therefore enable value creation opportunities for the wine industry based on a circular bioeconomy. This opportunity requires innovative research initiatives that focus on further elucidation of grape marc composition, along with the potential of PBNPs to form the basis for new applications at an industrial scale. In the context of potential health applications via inclusion in foods and beverages, previous research has demonstrated that wine grape PBNPs from red and white varietal marcs, to include Chardonnay, possess antioxidant and antimicrobial properties. (19,20) These properties offer a glimpse into the potential for wine grape marcs to serve as value-added ingredients in foods and beverages.
Given the scale of Chardonnay production in California and globally, Chardonnay marc could represent an opportunity for significant value creation as a food and beverage ingredient. Traditional uses of marc include distillation into spirits and as animal feed; with marc feed fortification shown to improve the antioxidant capacity and fatty acid profile of meat. (21−23) Additional applications of marc into the human diet can include the use of flours and seed products, such as oils and extracts. Marc can provide fiber, natural sugars, minerals, protein, lipids, and (poly)phenols. (24) However, differences in grape varietals, agricultural, postharvest handling, and processing practices can affect the composition of PBNPs for many food products. (25) Therefore, it is likely that varietal, extent of ripening, fermentation, and subsequent processing for food/dietary application can all impact PBNP composition. For example, Corte-Real et al. suggested that stabilizing the water content to reduce microbial growth is important as microbial spoilage of grape marc significantly reduces the phenolic content, while also highlighting marc from white wine grape varietals as being richer in polyphenols compared to red wine grape counterparts. (26) Finally, food-safe processing of grape marc requires specialized processing equipment and regulatory registrations to comply with global food safety initiative (GFSI) requirements.

Phenolic Compounds

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Wine grape phenolics and polyphenolics originate from phenylpropanoid pathway deamination of the aromatic amino acids phenylalanine and tyrosine to cinnamic acid. (27,28) In grape marc, this includes the phenolic acids, hydroxycinnamic and benzoic acids, polyphenols such as flavonoids (e.g., flavanols and flavonols), stilbenes, tannins, and lignin (29,30) (Figure 1). These PBNPs are diverse in structure and bioactivity potential, with substantial variation among wine grapes as well as other plant foods. Moreover, while any specific plant food can include a number of flavonoid subclasses, often only one will predominate. For example, cocoa flavanols are a significant source of (−)-epicatechin (epicatechin), (+)-catechin (catechin), and procyanidins up to ten degrees of polymerization (DP). In addition to epicatechin and catechin, tea is a significant source of gallocatechins, their gallic acid esters, and the polymers theaflavins, thearubigins, and theasinensins. (31,32) Differences in processing of flavanol-rich foods, such as marc, can also affect bioactivity. For example, prolonged heat treatment epimerizes epicatechin to less bioactive (−)-catechin. Importantly, specialized HPLC methodologies, such as chiral chromatography, are needed to detect this epimerization within foods, which have reduced bioactivity, as epicatechin cannot be resolved from its epimer using traditional methods. (33−35) This is an important consideration in terms of precision nutrition approaches, given that current recommendations for healthy dietary patterns are broad and diverse in terms of plant foods, and therefore the specific flavonoids present in overall diets would vary accordingly.

Figure 1

Figure 1. Production of Chardonnay grape berry phenolic acids and flavonoids from the metabolism of phenylalanine in the phenylpropanoid pathway. (171,172)

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Chardonnay marc contains hydroxybenzoic and -cinnamic acids, flavonols and flavanols, including oligomers of the monomeric flavanols, epicatechin, catechin, and other derivatives of catechin known as the procyanidins and proanthocyanidins. The so-called “French Paradox” of a low prevalence of coronary heart disease in the French population with a high fat diet, albeit controversial, was first attributed to the intake of all wine, (36) and later to the dietary intake of flavonoids present in red wine. (37) Unlike red varietals, Chardonnay marc is not a significant source of anthocyanins, with lower flavonol levels; however, it can provide similar, or even greater, amounts of flavanols. (38,39) For comparison, Rodriguez Montealegre et al. reported total monomeric flavanols in skin for Spanish Chardonnay, Cabernet Sauvignon, and Merlot at 28 ± 65 mg/kg, 23 ± 86 mg/kg, and 38 ± 21 mg/kg, respectively and in seeds at 730 ± 207 mg/kg, 430 ± 85 mg/kg, and 520 ± 128 mg/kg, respectively. Moreover, procyanidin B2 (i.e., two units of epicatechin) levels in Chardonnay and Cabernet Sauvignon seeds were 33 ± 5.8 mg/kg, and 41 ± 4.4 mg/kg, respectively. Also in Chardonnay seeds, a 2-fold greater amount of procyanidin B1 (i.e., one unit each of catechin and epicatechin) than Cabernet Sauvignon seeds (380 ± 5.8 mg/kg versus 150 ± 54 mg/kg, respectively). (40) A consistent finding is that greater amounts of (poly) phenols are present in the seeds compared to the skins for all wine varietals (26,41−43) (Table 1).
Table 1. Range of Phenolic and Polyphenol Content of Chardonnay Marc Skin and Seeds
phenolicskinaseedsaref
Hydroxybenzoic Acids
ellagic acid0.021.4–140 (167,173)
gallic acid0.04–120.5–152 (39,43,164,166−168,173)
gentistic acid0.6  (167)
p-hydroxybenzoic acid0.5–1.40.8 (164,167)
vanillic acid0.03–1.50.26–15.5 (43,168)
caffeic acid0.04–0.060.09 (164,167)
caftaric acid0.09–7.62.0 (38,165,166)
chlorogenic acid0.06–0.20.3 (164,167)
p-coumaric acid0.07–1.8  (164,167)
coutaric acid0.8–7.6  (38,165)
fertaric acid0.1  (38)
ferulic acid0.2–1.4  (164,167)
syringic acid0.07  (164)
dihydroquercetin-3-O-glucoside1.5–1.6  (164)
isorhamnetin-3-O-glucoside0.05–2.2  (38,164)
Hydroxycinnamic Acids
kaempferol0.06  (167)
kaempferol-3-O-galactoside3.6–7.7  (164,165)
kaempferol-3-O-glucoside0.8–26.8  (38,164,165)
kaempferol-3-O-glucuronide3.1–5.0  (164,165)
myricetin 0.2 (167)
myricetin-3-O-glucoside1.7–1.8  (164)
myricetin-3-O-glucuronide1.5–1 0.7  (164)
quercetin0.6–1.61.5 (164,167)
quercetin-3-O-galactoside14.6  (165)
quercetin-3-O-glucoside1.7–68.61.3 (38,165,166)
quercetin-3-O-glucuronide2.5–17.80.2 (38,165,166)
quercetin-3-rutinoside (rutin)1.2–6.20.2 (165−167)
quercetin-3-xyloside2.2  (165)
Flavanones
naringin0.080.2 (167)
hesperetin0.050.08 (167)
Flavones
apigenin 0.06 (167)
Flavanols
(+)-catechin0.04–60.03.3–1247 (38,39,43,164−168)
(−)-catechin gallate0.088.3–12.2 (43,167)
(−)-epicatechin0.01–445.1–1940 (38,39,43,164−168)
(−)-epicatechin-3-O-gallate0.2–0.33.9–62.6 (38,43,164,166)
(−)-epigallocatechin0.4–38.542.6 (43,164)
(−)-epigallocatechin gallate0.25–2.20.47–5.6 (43,167)
(−)-gallocatechin94  (43)
(−)-gallocatechin gallate1.29.9–26.6 (43,167)
Proanthocyanidins
dimer B148.938 (38,165)
dimer B237.03.3–251 (165,166)
dimer B3 5.2 (38)
dimer B4 7.1 (38)
galloylated dimers 980 (173)
total dimers (not galloylated) 89–5540 (173,174)
trimer18.510.3–22800 (165,173,174)
galloylated trimers 840 (173)
tetramers 10–1460 (173,174)
galloylated tetramers 560 (173)
pentamer 81.5–1170 (173,174)
hexamer 62.3–640 (173,174)
heptamer 65–650 (173,174)
octamer 61–420 (173,174)
nonamer 52–230 (173,174)
decamer 69–320 (173,174)
a

In mg/100 g.

Fiber and the Gut Microbiota

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PBNPs present in wine grape marc also include a complex carbohydrate fraction that can significantly impact both the health properties and sensory attributes of the material. Dietary fiber is a collective term for nonstarch and nondigestible polysaccharides, which includes the noncarbohydrate lignin, composed of phenolic compounds covalently bound to polysaccharides. (43−45) The general class of PBNP dietary fiber is complex with its definition constantly debated and refined, primarily due to the constraints and limitations in analytical chemistry, which impede a proper characterization and quantification of its individual components. (45) In an effort to harmonize the nomenclature, the Institute of Medicine (IOM) defined dietary fiber as nondigestible carbohydrate and lignin that is intrinsic and intact in plants, functional fiber as isolated nondigestible carbohydrate that has a functional physiological effect in humans, and lastly, total fiber as the sum of dietary and functional fiber. (46) Yet, an important aspect of fiber, not captured by these definitions, is the effect of fiber on the human gut microbiota. For instance, some fibers undergo extensive fermentation by the resident gut bacteria producing short chain fatty acids (SCFAs), whereas other fibers simply provide viscosity aiding to thicken the intestinal contents and slow transit time. (46) Short chain fatty acids such as acetate, propionate, and butyrate are produced in the colon, where they are used as preferential energy sources by intestinal cells. They also be systemically taken up via the portal vein to exert effects in organs and tissues as signaling molecules. (47)
States of fiber deficiency have not been established, with adequate intakes based on the median level of intake that lowers cardiovascular risk, which for adults is set at 14 g per 1000 kcal. (46) Yet, it is known that diets poor in fiber lead to reduced diversity in microbial populations and shift the overall metabolism from saccharolytic to proteolytic patterns, with the appearance of undesirable metabolites originating from extensive colonic microbial amino acid fermentation (known as putrefaction). (48) Additionally, detrimental functional changes have been demonstrated to take place in the intestine such as increased degradation of the protective mucin layer by the microbiota. (49) Therefore, the intestinal microbiota, made up of trillions of microbial cells, is increasingly being recognized as an important determinant of health, with nondigestible carbohydrates representing the prototypical ingredient that can provide a health benefit to the consumer over and above the inherent nutritional content. (50) It is not surprising that the gastrointestinal tract and its resident microbiota have become an important area of study for the development of novel PBNP. Commensal bacteria can provide a physical barrier that displaces pathogens from receptor binding sites on epithelial surfaces, can compete for available nutrients, and may also secrete antimicrobial agents that protect the host against exogenous pathogens. (51) To more accurately identify important carbohydrates for the gut, the Sonnenburg Lab (Stanford, CA) proposed the term “Microbiota-Accessible Carbohydrates” or MACs. (52) This nomenclature, if widely adopted by the scientific community, will allow us to differentiate the functional roles of indigestible carbohydrates and will prompt further investigation on the level of metabolic activity that a specific food can be expected to produce within a given microbiota, increasing our understanding of the “prebiotic selectivity” concept. (55)
Grape skin flour and seeds are rich sources of dietary fiber that ranges from 24 to 60%, with seeds containing greater amounts of fiber compared to the skin. (53) In terms of prebiotic activity, structure dictates the selectivity since consumption of a specific carbohydrate depends on the presence of genes for the breakdown into monosaccharide building blocks and their metabolism by gut bacteria. Overall, a higher diversity of monosaccharides is desirable as it is associated with greater selectivity in utilization by commensal bacteria. Cellulose, hemicellulose, pectin, and lignin make up the cell wall components of grape skin and seeds. In terms of structural properties, cellulose is a linear homopolysaccharide made of β(1–4) repeating glucose units, whereas hemicellulose is a heteropolysaccharide containing different monosaccharides in the backbone (both hexose and pentose sugars) further decorated by β(1–2), β(1–3), and β(1–6) linked side chains of galactose, arabinose, and glucuronic acid. Finally, pectin has an α(1–4)-linked galacturonic acid backbone substituted in certain regions with α(1→2) rhamnose units with additional side chains made of a diversity of monosaccharides (galactose, mannose, glucose, rhamnose, and xylose). (54) A recent analysis of seedless Chardonnay marc reports a 30% greater amount of cellulose compared to seeds isolated from marc (86.0 mg/g dw versus 60.6 mg/g dw, respectively) with 3-fold higher levels of hemicellulose in the seed component versus the seed-free marc fraction (78.6 mg/g dw versus 26.1 mg/g dw, respectively). Lignin contributes to the seed’s woody structure and was 7-fold greater in the seed component compared to marc without seed (364 mg/g dw versus 52 mg/d dw, respectively). (43) While pectin characterization was not part of that study, a recent optimization of pectin extraction from Chardonnay marc produced a polysaccharide fraction containing 55.7% homogalacturonan and 35.2% rhamnogalacturonan I (RG-I) with short chains or single units of arabinose and galactose (RG-1). (55)
Unlike other dietary components, the impact of dietary fiber on health is not dependent on its absorption and distribution to the tissues, but rather its impact on the alimentary tract, interaction with other dietary components, and the gut microbiota. Ultimately, the magnitude of its effect depends on the specific polysaccharide composition. For example, poorly fermented fibers, such as cellulose, provide bulk and have a laxative effect, whereas viscous fibers have a more profound influence in the upper gastrointestinal (GI) tract by slowing the transit of food. This reduces glucose absorption and inhibits bile acid reabsorption to lower plasma cholesterol levels. (45,56) Moreover, gut microbial metabolites, such as SCFAs produced from fermentable fibers can positively regulate cardiometabolic health. (57) While randomized, double-blind clinical trials are increasingly validating the health benefits derived from prebiotic use, the molecular mechanisms by which these approaches exert such an effect remain, for the most part, obscure. Oligosaccharides are one class of carbohydrates that has been rapidly gaining attention thanks to their multifunctional health properties. Oligosaccharides have a low degree of polymerization (e.g., 3 to 15 monosaccharide units), yet are a diverse class of compounds fermentable by select species of the gut microbiome. They are naturally present in mammalian milks and in many plants, after in vivo synthesis or through the hydrolysis of higher polysaccharides, glycoproteins, and glycolipids. Recent interest from the nutritional community in oligosaccharides derives from their unique added health benefits. For example, human milk oligosaccharides (HMOs) are known to play a critical role in the growth, stimulation, and cognitive development of the infant and, perhaps most remarkably, the establishment of the intestinal microbiome. (58) Several HMOs also share common structural motifs with oligosaccharides on the infant’s intestinal epithelia known to be receptors for pathogens. The presence of such structures imply that HMOs provide a defensive strategy, acting as decoys to prevent binding of pathogens to epithelial cells, thereby protecting infants from disease. (59) Comprehensive studies characterizing HMOs support the hypothesis that their structural complexity is the basis for a multitude of biological functions, the full range of which is only now beginning to be unraveled. In particular, bacterial fermentation of oligosaccharides requires specific activities of enzymes belonging to the glycosyl hydrolase family 20 (e.g., β-d-galactosidase, α-l-fucosidase, N-acetyl-β-d-hexosaminidases, etc.). (60) Remarkably, only a few select Bifidobacterium strains, such as B. longum subsp. longum, B. infantis, B. breve, and B. bifidum, possess the genetic capability to rapidly metabolize HMOs as the sole carbon source. (61) Therefore, extrapolating this reasoning to PBNPs, the identification of dietary sources or food waste streams that can offer a diversity of monosaccharide building blocks in polysaccharides and oligosaccharides is highly desirable. Yet, identification of the individual carbohydrate structures comes with numerous analytical challenges. The diversity of monosaccharides brings a complexity of structures, differentiated not only by the composition but also by the position of the many glycosidic linkages connecting the various building blocks. Liquid chromatography coupled with mass spectrometry (LC-MS) has emerged as the preferred tool to both resolve the many isomeric forms of oligosaccharides and decode their composition and structure. A typical workflow for liquid chromatography–mass spectrometry used to identify the oligosaccharides present in a grape sample and measure their abundances is presented in the (Figure 2).

Figure 2

Figure 2. Quantification can be conducted using peak heights or areas (label-free quantification) or by isotopic labeling strategies. Through analysis of tandem-MS data and comparison with authentic and high-purity analytical standards, specific oligosaccharide structures present in a sample can be deduced.

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The process of winemaking releases berry skin oligosaccharides from pectin and hemicellulose, and hence the overall composition may be dependent on varietal, enzyme activation during ripeness, winemaking style, and the application of commercial enzyme treatments to increase color. (62) Whether similar attributes affect the availability of oligosaccharides from the diet is currently unknown. Recent profiling of Chardonnay marc oligosaccharides by Sinrod and colleagues detected up to 36 distinct naturally occurring oligosaccharides between the marc, its fractions, and an extract of the seed. Eleven oligosaccharides shared between the seedless marc and seeds were abundant in hexose and pentose, potentially generated by cell wall arabinogalactan polysaccharides. Five oligosaccharides were unique to the seed but not the seedless marc, while nine additional oligosaccharides were unique to the seedless marc and not the seed. Further analysis of the monosaccharide building blocks of the oligosaccharides indicated that seedless marc oligosaccharides consisted of 11 units that were 81% hexose, predominately (72%) from glucose, with lower amounts of galactose and mannose. (43) Of interest, the monosaccharide fucose (which is one of the prototypical components of HMOs) was detected at a level of 3.65% followed by arabinose, glucuronic acid, galacturonic acid, ribose, and rhamnose. Although regularly studied separately, fiber/oligosaccharides, polyphenols, and phenolics can associate with one another, and potentially act synergistically, through phenolic/polyphenol inhibition of carbohydrate digestion by brush border enzymes or through the select promotion of beneficial bacterial species. (56,63,64) Indeed, brush border glucosidases are needed to deglycosylate flavonols prior to absorption. (65,66)
In summary, a comprehensive characterization of PBNP ingredients, such as Chardonnay marc PBNPs, is vital to determine the impact of this dietary component on human health. A major limitation in the interpretation of data from observational studies and dietary intervention trials is the lack of characterization of a food’s bioactives using validated methods that precisely characterize the test products. Given the imprecise nature of measuring food intake, and limited characterization of specific dietary components in food databases, ultimately, the identification of suites of biomarkers will aid in the identification of specific dietary components and patterns that are associated with positive health outcomes. (67,68)

Potential Contribution of Chardonnay Marc within a Healthy Dietary Pattern

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Since the late 19th century, a vast array of PBNPs have been studied for their effects on health, including those recognized as essential macro- and micronutrients. Earlier work in nutritional science defined the essentiality of micronutrients for normal reproduction and development, as well as reducing the risk of specific diseases observed after single-nutrient deficiencies. Albert Svent-Györgyi and others discovered synergistic relationships between essential nutrients, such as vitamin C, and certain flavonoids to include the flavanone from citrus, hesperidin, and the flavanol catechin. (69,70) By centuries end, observational data from the “monitoring trends and determinants in cardiovascular disease” (MONICA) project and the Seven Countries Study suggested that wine and higher intakes of flavonoid rich foods reduced the risk of development of cardiovascular diseases. (36,71,72) Research since has supported this concept that certain PBNPs, such as fiber and certain flavonoids, that do not fit the classical definition of “essentiality” are critical for optimal health. The PREDIMED (PREvención con DIeta MEDiterránea) trial provides considerable data on the impact of specific dietary components within a healthy dietary pattern on clinical outcomes and overall cardiometabolic health. For this trial, adults 55–80 years of age with cardiometabolic risk factors were assigned to a reduced fat dietary pattern or a Mediterranean diet with nuts or extra virgin olive oil for 4.8 years. In secondary analyses, those with the highest intake of flavanols (263 mg/d) and flavonols (124 mg/d), respectively, had a 64% and 42% reduction in major cardiovascular events (myocardial infarction, stroke, and cardiovascular death). At study entry, red wine, apples, and peaches contributed most to flavanol intake, while spinach, beans, and onions were the greatest providers of flavonol intake. (73) Moreover, a reduced risk for the development of type II diabetes was observed for those with the highest levels of flavanol, proanthocyanidin, and hydroxybenzoic acid intake, with protection greatest for obese men and overweight and obese women, with women having higher Mediterranean diet scores. (74)
Renaud and De Longeril paradoxically observed that individuals in countries with higher saturated fat intakes, such as France, also had lower rates of coronary heart disease. Observing that alcohol intake was also inversely associated with reduced platelet aggregation, they postulated that the high intake of wine in these regions protected against coronary heart disease, (36) a plausible hypothesis as endothelial cell and platelet activation are central in the development of chronic inflammation and cardiovascular diseases. (75) Using an animal model of coronary cyclic flow reduction, which measures the effects of aspirin on platelet activation induced coronary damage and stenosis, Folts and colleagues demonstrated that apart from alcohol, grape-derived PBNPs could themselves reduce platelet reactivity. (76) Moreover, the intake of 450 mL/d of Concord purple grape juice by healthy individuals for 1 week reduced the platelet aggregation response to low dose collagen (1 mg/mL) by 77%, while a similar amount of orange or grapefruit juice had no effect on platelet reactivity. (77) Endothelial activation or endothelial/vascular dysfunction is an early indicator of cardiovascular disease development. Noninvasive measures of vascular function and health, such as flow mediated dilation (FMD), have been associated with cardiovascular risk factors. (78) Two weeks of daily intake of purple grape juice (approximately 640 mL) improved FMD two hours after intake in coronary heart disease patients. (79) While intriguing, the grape juice for these experiments was not well characterized, and the relationship between the intake of grape juice derived bioactives and biological effects could not be confirmed.
Since then, numerous short-term randomized controlled dietary intervention trials using well-defined cocoa products have demonstrated that the intake of flavanols improves surrogate outcomes of cardiometabolic health. (80) Cocoa flavanols include the monomers epicatechin and catechin, procyanidins with up to ten DP of epicatechin units, and the methylxanthine theobromine. A meta-analysis of 15 trials estimated that FMD response improved by 1.17% with cocoa flavanol intake at an optimal level of 95 mg of epicatechin, 20 mg of catechin, and 710 mg of total flavanols. (80) Additional data demonstrates that purified epicatechin increases vascular function (81−83) to a greater extent than catechin. (33) Procyanidin intake apart from the monomeric flavanols does not improve vascular response but can reduce total cholesterol levels and contributes to circulating levels of microbial derived 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone metabolites (γVLM) by 54%. (40) Taken together, this body of work demonstrates that short-term intake of cocoa flavanols positively modulates physiologically relevant cardiovascular surrogate outcome measures. Ultimately, to demonstrate the impact of any dietary bioactive on health, longer term (years in length) dietary intervention trials that track clinical outcome measures (e.g., myocardial infarction, cardiovascular death, stroke, etc.) are necessary. The recently completed COSMOS trial randomized older adults (mean age 72 years) to either 500 mg of encapsulated cocoa flavanols (containing 80 mg of epicatechin) or placebo for a median of 3.6 years of follow up. The primary end point, a composite of total cardiovascular outcomes (i.e., myocardial infarction, stroke, coronary revascularization, cardiovascular mortality, carotid and peripheral artery surgery, and unstable angina requiring hospitalization) was not statistically significant (p = 0.11). However, per protocol, secondary analyses demonstrated a 27% reduction in cardiovascular death, and for those at the highest level of compliance (missed supplementation <8 days/month), cocoa flavanol intake reduced the primary outcome of total cardiovascular events by 15%. Although not a prespecified secondary analysis, major cardiovascular events (myocardial infarction, stroke, and cardiovascular death) was reduced by 16%. (4) It is noteworthy that this rigorous measure was also the primary outcome for the PREDIMED trial. (4,84)
Although interpreted with caution, the results of the COSMOS trial strongly suggest that cocoa flavanol intake can provide a health benefit. As with the PREDIMED trial, ancillary studies aim to identify potential mechanisms of action and specific populations that may warrant cocoa flavanol supplementation. Certainly, an analysis of the potential impact of diet on the outcomes would be of value, as interactive effects between cocoa flavanols and other dietary components have been reported. This includes methylxanthines within cocoa products, such as theobromine and caffeine, (83,85) which can enhance both the vascular response and circulating levels of epicatechin metabolites after cocoa flavanol intake. (83) The synergistic effects from methylxanthines may not be limited to cocoa flavanols, but tea as well, since plasma caffeine levels were associated with FMD response after green tea intake. (86) It is noteworthy that theobromine has a longer half-life, and along with the caffeine metabolite paraxanthine, inhibition of phosphodiesterase and adenosine receptors are their commonly ascribed bioactivity. (87,88) Inhibition of phosphodiesterase potentiates the activity of the endothelial derived vasodilator nitric oxide. (89) Moreover, methylxanthine metabolism by cytochrome P450 (CYP) oxidases such as CYP2E1 can serve as another potential point of dietary interaction as this isoform is inducible by ethanol and inhibited by the intake of the flavonol quercetin. (87,90) Healthy dietary patterns include increased intake of green leafy vegetables that are high in dietary nitrate. The intake of nitrate (3 mg/kg bw) and cocoa flavanols (2.7 mg/kg bw) significantly enhanced vascular response. Importantly, the vascular response observed was not further enhanced with a higher intake level of nitrate and cocoa flavanols (8.5 mg/kg bw and 10.9 mg/kg bw, respectively). (91) Taken together, one can postulate that synergies between flavanol intake and other dietary components may explain the inverse associations observed between the intake of foods containing flavanols, such as grape products, tea, apples, and berries, and cardiovascular outcomes in both the PREDIMED and the European Prospective into Cancer (EPIC) trials. (67,73) The EPIC trial established γVLM as a potential biomarker of flavanol intake, demonstrating a negative correlation between this biomarker and blood pressure. Compared to those with lower γVLM levels, men and women in the highest decile of urinary γVLM had a −1.9 mmHg (95% CI: −2.7; −1.1) and −2.5 mmHg (95% CI: −3.3; −1.8) lower blood pressure, respectively. (67) Based on current food composition data, the authors estimated that those in the highest levels of flavanol intake consumed at the minimum 148 mg/day of total flavanols and 4 mg/day of epicatechin, with maximal intake estimated at 618 mg/day and 138 mg/day of flavanol and epicatechin, respectively. Mean intakes for both flavanols and epicatechin were estimated at 260 and 36 mg/day, respectively. (67) While encapsulated cocoa flavanol intake can certainly achieve these levels of intake, a combination of foods within a healthy diet such as apples, berries, wine, and tea may also provide similar flavanol levels. (67,73) For PBNP ingredients such as Chardonnay marc, with estimated epicatechin levels at approximately 0.9 mg/g, and up to 9 mg/g in the seeds, (43) a daily serving of 2 teaspoons can provide up to 20% of the mean predicted flavanol intake level achieved by individuals in the EPIC cohort. (67)

Data from Dietary Intervention Trials of Grape Berries, Juice, Powders, or Marc

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The complex mixture of PBNPs within marc, grape fruit, juice and powder has shown positive effects on cardiovascular outcomes in a number of dietary intervention trials (Table 2). Significant improvements in FMD response of 1 to 6.5% from baseline were observed after 2–4 weeks of daily intake of 240–640 mL of commercial “purple” or Concord grape juice (CGJ) by smokers, (92) those with hypercholesterolemia, (93) or those with documented coronary artery disease. (79,94) In individuals with prehypertension, 8 weeks of daily intake of CGJ providing 965 mg of total phenols (units not defined) and lowered systolic and diastolic nocturnal dip blood pressures by 1.4% and 1.5%, respectively, (95) which is important as a “non-dipping” nighttime blood pressure pattern is a predictor of increased cardiovascular events and mortality. (96) However, daily CGJ intake did not affect the 24 h ambulatory and office blood pressure, digital microvascular function, or pulse wave velocity (PWV). (95) Three to four weeks of daily intake of 36–46 g of a standardized freeze-dried grape powder (FDGP) mixed into water increased FMD response in healthy individuals and those with metabolic syndrome. The FDGP, produced from red, green, blue-black seeded, and seedless California table grapes, provided 208–267 mg of total phenols (gallic acid equivalents, GAE), 1.3–1.7 mg of flavonols, and 378–483 mg or approximately 8–10% of the daily value (DV) of potassium. (97,98) These improvements in vascular outcomes may be due in part to reductions in inflammation and oxidative stress, which positively modulates vascular mediators, such as nitric oxide or the potent vasoconstrictor endothelin-1. Indeed, a reduction in proinflammatory mediators, interleukin (IL)-1β, nicotinamide adenine dinucleotide phosphate oxidase (NADPH) oxidase, and soluble intercellular adhesion molecule (sICAM)-1, have been reported after daily intake of FDGP, (97,99) grape juice, (100−102) and black table grapes. (103)
Table 2. Cardiometabolic Outcome Results from Dietary Intervention Trials Using Grape Productsa
grape productsample size (M/F)target populationmean ageRCT designdurationinterventioncontroltotal polyphenols (GAE)major flavonoids (mg)resultsref
marc49 (27/22)adults, MetS42.6crossover6 wk, 4 wk WO8 g marc in waterno marc  ↓fasting insulin and HOMA-IR; ↑QUICKI (133)
 27 (27/0)adults, with one MetS component43.6controlled, nonrandomized crossover4 wk, 4 wk WO7% marc in burgerno marc in burger121 ↓fasting glucose, HOMA-IR, oxLDL,; ↑plasma vitamin C (175)
 12 (12/0)healthy adults26randomized, controlled crossover5 h PP, 1 wk WOred grape pomace drinkIC control156270% A, 23% F, 4% P↓GP iAUC insulin vs control (176)
freeze-dried grape powder20 (4/16)obese adults48.6controlled, double-blind crossover; short-term intake + PP response with intervention and a high fat and carbohydrate meal4 wk, 2 wk WO; PP 5 h60 gIC, MAC matched, POLY–2971.4 E/1.4 CPP: ↓ET-1 (5 h); ↑NRF2 (99)
 25 (25/0)adults, MetS51.3controlled, double-blind crossover30 days; 3 wk WO46 gIC, MAC matched, POLY–2670.14 mg Q, 35 A↑FMD GP vs control; ↓sICAM-1 vs control (97)
 19 (7/13)healthy adults33.5low polyphenol diet run-in, followed by single arm intervention4 wks, 3 wk WO46 gPOLY– diet1630.11 E, 0.67 C↓Total-C, HDL-C, total BA (104)
 5 (5/0)young adults24controlled, nonrandomized3 wks36 gIC, POLY–  ↑FMD GP vs control, with and without high fat meal (98)
 44 (0/44)pre- and postmenopausal women39.7 (pre), 58.5 (post)randomized, single blind, controlled crossover4 wks, 3 wk WO36 gIC, POLY–209 ↓triglyceride, LDL-C, apo B and E, TNFα, isoprostane (105)
 33 (11/22)obese adults34.7 (F), 37.1 (M)randomized, double blind, controlled, crossover3 wks, 2 wk WO46 gMAC matched0.58 E, 0.88 C, 2.26 Q, 26.9 A ↓GP large LDL-C and particles vs control; ↑GP IL-1b, IL-6 from activated PBMC vs control (177)
juice22 (18/4)documented CAD64parallel arm, dose response4 wks320, 640 mL PGJ   ↑FMD from baseline, no significant difference between intake levels (94)
 16 (8/8)adults, hypercholesterolemia51.6crossover2 wks, 2 wk QO500 mL/day PGJRW 250 mL  GJ: ↑FMD GP, ↓sICAM-1 vs baseline (93)
 64 (44/20)prehypertensive or stage 1 hypertension43double blind, controlled, crossover8 wks, 4 wk WO490 mL/day CGJIC965 mg NS PAT, PWV; ↓glucose, ↑systolic and diastolic nocturnal dip BP (95)
 20 (12/8)healthy adults30.6single arm2 wks490 mL/day PGJnone  ↓PMA, ADP, collagen-induced platelet aggregation, superoxide; ↑NO (178)
 10 (5/5)healthy adults42crossover1 wk, 1 wk WO450 mL/day PGJorange and grapefruit juice1000 mg GJ: ↓collagen-induced platelet aggregation (77)
 40 (40/0)stage 1 hypertension43parallel arm, double-blind, controlled8 wks420 mL/day PGJIC885 ↓systolic and diastolic BP (179)
 15 (12/3)documented CAD62.5single arm2 wks640 mL/day CGJnone  ↑FMD and lag time for LDL oxidation (79)
 53 (24/29)healthy adults and hemodialysis patients62.0 (juice group)parallel arm14 days100 mL/day RGJnone6404.13 Q3R, 3.13 M, 0.02 C, 12.4 mg A↓LDL-C, apoB100, ox LDL; ↑HDL-C, apoA-I, alpha-tocopherol (102)
 18 (6/12)healthy adults and those with type II diabetes56 (type II diabetes patients)parallel arm4 wks150 mL/day MJ, M wine and M dealcohlized winenone  NS observed for MJ intake (180)
 32 (16/16)hemodialysis patients randomized, parallel arm 100 mL/day RGJnone  ↓LDL-C, apoB100, NADPH oxidase, MCP-1; ↑HDL-C (101)
 76healthy adults22 (CGJ group); 26 (control group)double blind, controlled, parallel arm12 wks240 mL/day CGJIC, no treatment467153 mg P+F; 96 A↑CGJ OGTT vs baseline, no significant between group effects (181)
 26 (10/16)healthy smokers26randomized, double-blind controlled, crossover2 wks, 4 wks WO240 mL/day CGJIC, color matched grapefruit juice473 ↑FMD CGJ vs control, post smoking FMD vs control; ↓PWV CGJ vs control (92)
 26 (10/16)healthy smokers randomized, double-blind controlled, crossover2 wks, 4 wks WO240 mL/day CGJIC, color matched grapefruit juice473 ↓CGJ smoking induced ICAM-1 and PAI-I vs control (100)
 39 (24/15)hemodialysis patients62.9randomized parallel arm3 times per wk for 6 mo100 mLnone589152 A↓total cholesterol from baseline in both groups (106)
 28 (23/5)healthy adult runners39.5parallel arm28 days10 (mL/kg)/d GJ (Isabel, Bourdeux, Concord varietals)12740.7 E, 21.1 C, 36.8 A, 3.43 PB1, 5.29 isoquercetin ↓GJ systolic BP, total-C, LDL-C vs baseline; ↑GJ HDL-C vs baseline (107)
fruit69 (14/55)adults, hypercholesterolemia51.2randomized, parallel arm8 wks500g Condori red or Sharoodi white grapes5 servings of fruitRG 0.652 ± 0.23 vs WG 0.598 ± 0.18 mg/g dw ↓total-C, LDL-C RG and WG vs baseline (108)
 30 (16/14)healthy adults31.5parallel arm3 wks, with 4 wk follow up5 g black table grapes/kg bwnone  ↓IL-1β, procoagulant activity, no change in lipid or glucose outcomes with grape intake (103)
a

Abbreviations: A, anthocyanidin; apo, apoprotein; ADP, adenosine diphosphate; BA, bile acids; BP, blood pressure; C, catechin; CGJ, Concord grape juice; E, epicatechin; ET-1, endothelin-1; FMD, flow mediated dilation; F, flavanols; GJ, grape juice; GP, grape pomace; HDL-C, high density lipoprotein-cholesterol; HOMA-IR, Homeostatic Model Assessment for Insulin Resistance; iAUC, incremental area under the curve; IC, isocaloric; ICAM, intercellular adhesion molecule; IL, interleukin; LDL-C, low density lipoprotein-cholesterol; MAC, macronutrient; MetS, Metabolic syndrome; MCP, monocyte chemoattractant protein; M, muscadine; MJ, muscadine juice; NADPH, nicotinamide adenine dinucleotide phosphate; NO, nitric oxide; NRF2, nuclear factor E2-related factor 2; NS, not significant; OGTT, oral glucose tolerance test; oxLDL, oxidized LDL; PAI, plasminogen activator inhibitor; PAT, peripheral arterial tonometry; PB1, procyanidin B1; PBMC, peripheral blood mononuclear cell; PGJ, purple grape juice; PMA, phorbol myristate acetate; POLY–, low polyphenolic; PP, postprandial; PWV, pulse wave velocity; Q, quercetin; QUICKI, quantitative insulin sensitivity check index; RG, red grape; RGJ, red grape juice; RW, red wine; TNF, tumor necrosis factor; WG, white grape; wk, week; WO, washout.

Moreover, grape product intake has consistently improved lipid profiles. Reduced levels of total- and/or LDL-cholesterol have been observed with the short-term intake of FDGP, (104,105) grape juice, (101,102,106,107) and red (103,108) and white grape varietals. (103) A recent meta-analysis by Lupoli and colleagues of 24 published articles with 587 volunteers in randomized, controlled trials (RCTs) reported −7.6 mg/dL, −6.3 mg/dL, and −14.5 mg/dL reductions in total- and LDL-cholesterol and triglycerides, respectively, with grape product intake (i.e., marc, FDGP, GJ, or grape seed extracts). Moreover, after stratifying by grape product, only those individuals consuming marc and FDGP significantly reduced LDL-cholesterol (−6.3 mg/dL; 95%CI: −11.0, −1.6, p = 0.01). (109) It is important to recognize that a majority of the studies to date have provided limited data from strictly white varietals, with a majority of data derived from red grape varietals or mixtures of varietals containing red varietals that provide the flavonoid subclass anthocyanins not present in significant amounts in white varietals. Anthocyanins provide berry color and are thought to contribute to the positive health outcomes after berry intake, (110,111) with circulating phenolic anthocyanin metabolites of benzoic and cinnamic acids having the strongest associations with vascular response. (110)
Specific to Chardonnay, Corban et al. recently reported improvements in the reactive hyperemia index (RHI; EndoPAT2000), a measure of digital microvascular function, with 4 months of daily intake of either a defatted and milled Chardonnay grape seed flour or a comparative capsule with matched macronutrients, where the fat was matched with organic grape seed oil. The study participants were recruited from a cardiovascular outpatient population and clinic employees and were relatively young (mean age about 38 years) and predominately female, with cardiovascular risk factors controlled with medication and having “endothelial dysfunction” or a low baseline RHI (<2.0) at study entry. (112) In this population, systolic blood pressure was reduced 3 mmHg from baseline in both groups. Blood cholesterol levels did not significantly change over time, except for an 8% increase and an 11% decrease in triglycerides in Chardonnay grape seed flour versus comparator, respectively. The provision of 4.6 g of Chardonnay grape seeds each day provided 528 mg of total phenols (GAE) and were composed of 57% fiber, 1.3% monounsaturated fatty acids (MUFA), and 4.3% polyunsaturated fatty acids (PUFA). The comparative capsule was designed to be low in total polyphenols (approximately 4.8 mg/day) but still provided appreciable amounts of fiber (26%), MUFA (2.7%), and PUFA (4.2%). The study results suggest that dietary components beyond the phenolic content may contribute to the observed vascular response. In addition to fiber and PUFA, other bioactives provided by the grape seed oil may include vitamin E and phytosterols. (113)

Supportive Data from Animal Models

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Data from a hypercholesterolemic hamster model, a model that compared to other rodent models best reflects human hepatic cholesterol and bile acid metabolism, demonstrated lower total-, LDL-, and VLDL-cholesterol levels with Chardonnay grape seed flour intake. (114−116) In the first study, ten animals each consumed for 3 weeks Chardonnay, Cabernet Sauvignon, and Syrah seed flours, all sourced from Sonoma County, California. The Chardonnay seed flour was 1.4- and 1.9-fold greater in total flavonoid content, and 7.2- and 7.6-fold greater in epicatechin content than the Cabernet and Syrah seed flours, respectively. Compared to a control hypercholesterolemic diet, 3 weeks of a hypercholesterolemic diet containing 10% Chardonnay seed flour lowered total-, LDL-, and VLDL-cholesterol by 38%, 56%, and 73%, respectively, and lowered the expression of pro-inflammatory genes for tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1 in adipose tissues, whereas the Cabernet Sauvignon or Syrah seed flour diets did not significantly affect circulating cholesterol levels relative to control. (116) Overall, the cholesterol lowering effects were related to changes in the expression of genes that regulate hepatic fatty acid, cholesterol and bile acid metabolism, specifically a decrease in the intestinal expression of fibroblast growth factor (FGF) 15, which is regulated by Farnesoid X Receptor (FXR) signaling, a negative regulator of cytochrome P450 (CYP) 7A1. In agreement, animals that consumed the Chardonnay seed flour had increased expression of CYP7A1, a positive regulator of bile acid production. (116,117) These observed beneficial hepatic effects were repeated in a mouse model of nonalcoholic fatty liver disease (NAFLD), where improvements in insulin sensitivity and a positive modulation of genes associated with oxidative stress, inflammation, and immune response were reported. (115) For a select number of bacteria, the authors observed an overall reduction in the number of fecal bacteria in hamsters fed a high fat diet with 10% Chardonnay or Cabernet Sauvignon marc. Specifically, relative to control, they observed increased levels of Bacteroides fragilis and reduced levels Lactobacillus spp and Bifidobacterium spp, as well as, reduced Firmicutes/Bacteroidetes (F/B) ratio with 3 weeks of Chardonnay marc feeding. The intake of Cabernet Sauvignon decreased Enterobacteriacae. In addition, significant and strong positive associations between Lactobacillus spp and LDL- and total-cholesterol were observed. These observations demonstrate the potential for marc products to influence the microbiome. However, they also illustrate the challenge of associating changes in specific bacterial populations with physiologic/metabolic outcomes as Lactobacillus species have been reported as either positive or negative toward cardiovascular health. (118,119)

Grape Marc PBNPs, Microbial Metabolites, and Health

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In its role protecting the host from the environment, the gastrointestinal tract is the largest immune organ in the body, containing trillions of bacteria and associated genes. There is considerable interest in defining diet–gut–microbiota interactions that influence health and an individual’s susceptibility to disease. (119,120) The central nervous system (CNS) regulates physiological homeostasis through environmental peripheral “sensing” afferents located throughout the body, including the gut, that involuntarily regulates the cardiovascular system and visceral organs via the sympathetic and parasympathetic efferent arms of the autonomic nervous system. Moreover, circulating microbial derived metabolites, such as bile acids and SCFAs, produced from fiber fermentation products, and phenolic/polyphenolic metabolites can regulate gut integrity, along with host immunity and metabolism. (117,121,122) Therefore, crosstalk between dietary components and the microbiome has the potential to impact overall gut, brain, metabolic, and cardiovascular health. (119,120) Cholesterol 7α-hydroxylase, also known as CYP7A1, synthesizes bile acids from cholesterol. After conjugation with taurine or glycine the resulting bile salts are stored in the gall bladder and released into the gut with food intake to emulsify dietary fats and aid in both fat and fat-soluble vitamin absorption. Approximately 95% of the bile acids are enterohepatically recirculated with the remaining excreted in the feces. In addition, certain gut bacterial species contain bile salt hydrolase (BSH), bile acid inducible, and bile acid dehydratase enzymes that can produce deconjugated bile acids. Bacterial deconjugation produces more hydrophobic bile acids with limited absorption, and higher fecal excretion. (117) For those that are absorbed, further transformation in the liver and kidney produces secondary/tertiary bile acids that represent 35% of the bile acids in circulation. These bile acids are of interest for their ability to activate nuclear receptors such as FXR to regulate a number of metabolic processes, including glucose and lipid metabolism. (117,123)
Both dietary fiber and polyphenols can sequester conjugated bile acids, which limits bile acid absorption, making them more accessible for bacterial deconjugation in the colon. This may explain, in part, the lipid lowering effects of grape products. (109,117,123) Healthy adults that were instructed to add FDGP to a low fiber and polyphenol diet for 4 weeks reduced their total and HDL cholesterol levels. In these individuals, the authors reported a significant reduction in total serum bile acids, with reduced levels of the primary bile acid glycochenodeoxycholic acid (GCDCA) and secondary bile acids glycodeoxycholic acid (GDCA) and taurodeoxycholic acid (TDCA). (104) Moreover, the changes in both GDCA and TDCA were positively associated with the fecal presence of Actinobacteria, a phylum identified as having glycine conjugation capability as well as BSH activity. (124) While the mechanism of action could not be defined, these data are consistent with in vitro findings of TDCA and GDCA binding by phenolics typically found in grape products such as gallic acid, catechin, and epicatechin. (125) Bacterial strains with BSH activity also have the capacity to ferment fiber into SCFAs, such as propionate, and can suppress 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR) the rate-limiting enzyme for cholesterol synthesis. SCFAs produced from fiber fermentation may also help clear cholesterol through activation of sterol regulatory element-binding protein (SREBP)-2 to increase hepatic LDL-receptor gene expression. (117) Additional proposed benefits of SCFAs include stimulation of satiety hormones and improved gut barrier function and glucose homeostasis with overall dietary composition influencing SCFA profile. For example, reduced blood pressures were reported within a DASH dietary pattern when carbohydrate was replaced with either unsaturated fat or plant-based protein. (126) Although all three diets provided a high level of dietary fiber, circulating levels of total SCFAs, acetate, and propionate were greatest with higher intake of plant protein within the DASH dietary pattern. Moreover, acetate was associated with lower fasting glucose and insulin levels, while propionate and butyrate were associated with lower HDL cholesterol, suggesting that cardiometabolic health is dependent on SCFA species. (127) Importantly, compared to fecal SCFAs, circulating levels of SCFAs are best associated with markers of metabolic health; (128) however, fecal SCFA levels may provide additional data on overall gut health, particularly as SCFAs such as butyrate are known to regulate intestinal cell proliferation and overall gut barrier function. (122) Moreover, there is recognition that gut dysbiosis may have a critical role in the origin of a number of diseases, including neurological conditions such as Parkinson’s Disease, the severity of which may be evaluated through the measurement of both plasma and fecal SCFAs. (129,130)
Studies on the relationship between improved glucose homeostasis and SCFAs after grape marc intake are currently limited. Significantly lower blood pressure, fasting blood glucose, and propionic acid levels were reported when individuals were asked to reduce salt intake through the incorporation of 2 g of Tempranillo marc seasoning into diets providing 810 mg/g of complex polysaccharides and 19 mg/g of fiber for 6 weeks. (131) Branch chain amino acids play a critical role in the regulation of protein synthesis yet are dysregulated in individuals with obesity and diabetes. (132) Individuals with at least two components of metabolic syndrome (i.e., BMI > 25 kg m2; fasting glucose ≥ 100 mg/dL 1; HDL-cholesterol ≤ 50 mg/dL in women and ≤ 40 mg/dL in men; triglycerides ≥ 150 mg/dL; systolic blood pressure ≥ 130 mmHg or diastolic pressure ≥ 85 mmHg) consumed 8 g of Tempranillo marc every day for 6 weeks. The marc was 68% dietary fiber and 29% total phenols. Overall, marc intake improved fasting insulin levels and sensitivity and increased fecal Bacteroides, while reducing the fecal excretion of the branch chain SCFA isovaleric acid. However, when the study population was split into those that had at least a 10% decline in fasting insulin levels (i.e., “responders”) versus those who did not (i.e., “non-responders”) a reduction in Bacteroides abundance was observed, with no significant change in fecal SCFA levels. Moreover, prior to marc intake the “responder” group had significantly lower Firmicutes abundance and tended to have lower levels of butyrate and valeric acid relative to the non-responders. Although of interest, the participants were asked to participate in a low phenol diet 3 days prior to each study visit, therefore it is unknown what impact the study participants’ habitual diet had on the study outcomes. (133,134)
Key to assessing the potential bioactivity of Chardonnay marc PBNPs is an understanding of the bioavailability, metabolism, tissue distribution, and excretion/elimination of (poly)phenols. This includes the potential interactive effects within either the marc or other dietary components that may affect both absorption and bioactivity. Monomeric flavanols are readily absorbed into the enterocyte, whereas glycosylated flavonols (e.g., quercetin glycosides) are hydrolyzed to the parent aglycone prior to absorption. This is achieved by either lactase phlorizin hydrolase located on the brush border membrane or hydrolysis after transportation into the enterocyte by sodium-glucose co-transporter 1 (SGTL-1) by β-glucosidase. (135) Flavonol aglycones immediately undergo phase I metabolism (e.g., oxidation, reduction, and hydrolysis reactions), while both flavonols and flavanols undergo phase II metabolism at the level of the intestinal epithelium or in the liver to the major circulating forms as sulfate, glucuronide, and methylated conjugates. (136) Once absorbed, flavonoids may also be effluxed apically back into the intestine or transported in the bile from the liver into the intestine, followed by deconjugation and colonic metabolism into a series of phenolic metabolites. (137−139) Larger molecular weight condensed tannins, such as procyanidins greater than trimer, do not undergo gastric hydrolysis (40) but are accessible for metabolism by gut microbiota. Moreover, rhamnose containing flavonols are not absorbed in the small intestine but are hydrolyzed by bacterial rhamnosidases in the colon. (135) In addition to bile acid sequestration, polyphenols, fiber, and protein interact with one another, within the food matrix and gastrointestinal track, which may affect bioaccessibility. (140) Indeed, the concept of “missing” dietary polyphenols is that certain polysaccharide/polyphenol interactions are not characterized by standard polyphenol extraction methodologies. (140,141) Therefore, polyphenols not bound to dietary fiber are immediately available for absorption, while polyphenols associated with fiber can reach the colon for bacterial metabolism. (140) Likewise, interactions of phenolics and polyphenols with pancreatic amylase and intestinal brush border enzymes may prevent partial hydrolysis of oligosaccharides in the small intestine. (63) Finally, considerable interindividual differences in microbial epicatechin metabolism have been reported, with the influence of phylotype on epicatechin bioactivity yet to be explored. (137)

Role of Computational Methods in Accelerating PBNP Research and Innovation

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Developing new classes of upcycled co-products rich in PBNPs with positive impacts on health and environmental sustainability is a significant societal grand challenge. However, this important opportunity is severely constrained by the extraordinary complexity of PBNP mixtures in byproducts produced during processing of plant-based raw materials, coupled with the need for rigorous identification of bioactivity relevant for commercial value creation. The resource intensity associated with successfully executing this type of research and development activity is traditionally associated with the pharmaceutical and flavor and fragrance industries, with complementary basic research efforts existing in the university and government sectors. Transformative advances in science and technology associated with analytical chemistry, biology, biochemistry, genomics, and computational methods offer a new approach to accelerating research and innovation in this area, while simultaneously significantly reducing resource requirements. Central to this approach is integration of a data science strategy enabling high quality predictions based on artificial intelligence capabilities. When successfully executed, this strategy can multiply the value of relatively sparse chemical, biological, and physiological data while simultaneously reducing the risk inherent in human subject experiments required for confirmation of efficacy regarding health or sensory attributes of specific PBNPs. The use of computational methods to accelerate innovation in human health and the gut microbiome has received special attention during the past decade, including the potential influence of diet, and advances in this area can have application for PBNPs. (142)
Simmons et al. (143) offered a glimpse into the potential of this approach for accelerating research regarding PBNPs present in Chardonnay marc. These investigators integrated publicly available natural products chemistry data sets related to wine grape marc from different varieties, including Chardonnay marc specifically, to investigate their differences and potential implications to human health through a network-based meta-analysis. Chemical composition data was aggregated from publicly available literature, and potential health effects were then identified based on this chemical information and associations between disease states. From currently available data from 132 studies, the analysis was able to differentiate five overabundant compounds present in Chardonnay marc versus other red and white varietal grape marcs. This included the flavanols discussed above, catechin, epicatechin, epigallocatechin, gallocatechin, and proanthocyanidin C1 and determined that gallocatechin was unique to Chardonnay marc. Subsequent analysis with these compounds of 934 studies of 358 disease states and 34 disease classes was able to confirm that these compounds were positively associated with cardiovascular disease outcomes. (143) Although Chardonnay marc is not widely studied at present, the general framework of network-based meta-analysis utilizing natural products composition information provided a holistic view of the knowledge space for wine grape marc and suggested potential areas of focus for future research programs.

Deciphering the Flavor Chemistry of Chardonnay Marc: An Epicurean Delight

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An exciting and promising discovery for the food and beverage industry is that the extraordinary diversity of bioactive PBNPs that are relevant to human health in Chardonnay marc also contribute to a wide range of desirable sensory attributes. Chardonnay marc has recently gained popularity as a flavorful new food ingredient with its velvety texture, mild astringency, slightly sour taste, and subtle floral and fruit-like aroma attributes. Grape marc has been evaluated as an ingredient in a wide variety of foods. Some examples include baked goods, such as wheat bread and breadsticks, pasta, various beverages, and even chocolate. (144−149)
Some popular health foods and dietary supplements such as pomegranate extract, green tea extract, cocoa extract, and others that are in high demand in the natural foods industry but whose flavor is generally not well accepted by consumers for use directly in foods are often sold in the form of capsules or pills that can be swallowed. Often, this failure of use directly as a food ingredient is due to their strong bitterness, astringency, and various other unpleasant off flavors such as strong vegetative or beany flavors. To include these ingredients directly in foods like beverages or drink powders, much effort has gone into the development of technology that mitigates these undesirable flavor issues. Some of these technologies include encapsulation, absorption of the materials onto protein, and the utilization of bitter-masking agents to increase the consumer enjoyment of these products. (8,150−152) For Chardonnay marc, such a trend appears to be an exception, as Chardonnay marc is a rich source of PBNPs, similar to other plant-based supplements but has a pleasant flavor, low in bitterness and astringency, and appealing fruity and floral raisin-like retronasal aroma attributes. Not only can Chardonnay marc be used directly as an ingredient in food products and accepted by consumers, but in some cases the addition of Chardonnay marc to foods, such as chocolate, appears to enhance the flavor, which consumers seem to prefer. (149)
When a food is consumed, aroma, taste, and chemosensory sensations are perceived simultaneously and not as discrete events. However, due to the very different nature of the molecules, each requiring a different array of purification and analytical methods, sensory-active compounds are often studied separately. In addition, it has long been overlooked that only a minor fraction of the volatiles present in a food are able to interact with odorant receptors present in the human olfactory system. The molecular sensory science approach termed sensomics, can be used to distinguish the aroma active compounds present in a mixture of odorless volatiles. (153) Sensomics approaches start with careful isolation of the volatiles by means such as SAFE distillation (solvent assisted flavor evaporation) followed by the application of Aroma Extract Dilution Analysis (AEDA). (154) Odorants identified with high Flavor Dilution (FD) factors are then accurately quantitated by the application of a gold-standard quantitation method such as Stable Isotope Dilution Assay (SIDA). Finally, the use of an aroma stimulation model can account for interactions among odorants and aroma released from the food matrix. Here, reference odorants are mixed into a model food matrix in the “natural” concentrations measured in the food, with the identification and quantitation of the aroma compounds considered successful if this aroma simulation model mimics the overall food aroma when evaluated through human sensory analysis. (154)
In a recent study applying a sensomics approach to the skin component of Chardonnay marc, thirty-five odorants were identified, with 13 odorants quantitated with SIDA, and odor activity values (OAV) were calculated (Table 3). Odorants with OAVs > 1 included 3-methylnonane-2,4-dione (hay, OAV 5800), β-ionone (floral-violets, OAV 2900), (2E,4E)-nona-2,4-dienal (fatty, OAV 1200), β-damascenone (cooked apple, OAV 370), hexanal (green, OAV 260), oct-1-en-3-one (mushroom, OAV 200), linalool (floral-citrus, OAV 61), (2E,4E)-deca-2,4-dienal (fatty, OAV 60), 2-phenylethanol (floral-rose, OAV 16), 3-(methylsulfanyl)propanal (potato, OAV 3.7), 4-hydroxy-2,5-dimethyl-3(2H)-furanone (HDMF) (caramel, OAV 2.0), and ethyl octanoate (fruity, OAV 1.1). An odor simulation model prepared using reference odorants with OAVs > 1 was a close match sensorially to the aroma of the Chardonnay marc skins. Accordingly, this collection of odorants was determined to play an important role in the pleasant aroma quality of Chardonnay marc skins. (155) In another recent study applied to the seed component of Chardonnay marc, forty-three odorants were identified including six with flavor dilution (FD) factors ≥64. The odorant with the highest FD factor was (2E,4E)-deca-2,4-dienal (fatty) with an FD factor of 1024. Five other odorants were identified with an FD factor of 64 including hexanal (green), linalool (floral, citrus), (2E,4E)-nona-2,4-dienal (fatty), 3-methylnonane-2,4-dione (hay-like), and 2-phenylethanol (floral, rose). (156)Figure 3 presents the structures and odor descriptors. Based on the results, these odorants may contribute to the overall aroma of the seeds; however, additional quantitative studies are required to support this hypothesis.

Figure 3

Figure 3. Structures and odor descriptors of odorants identified and quantitated in Chardonnay marc skins with OAVs > 1. (155)

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Table 3. Odorant Name, Odor Quality, and Odor Activity Value (OAV) of Odorants Quantitated in the Skin Component of Chardonnay Marc
odorant nameodor qualityOAVa
3-methylnonane-2,4-dionehay5800
β-iononefloral, violet2900
(2E,4E)-nona-2,4-dienalfatty1200
β-damascenonecooked apple370
hexanalgreen260
oct-1-en-3-onemushroom200
linaloolfloral, citrus61
(2E,4E)-deca-2,4-dienalfatty60
2-phenylethanolfloral, rose16
3-(methylsulfonyl)propanalpotato3.7
HDMFcaramel2.0
ethyl octanoatefruity1.1
pentanoic acidrancid<1
a

OAV = odorant concentration/odorant threshold in water. (155)

Although a few studies have been conducted on the aroma chemistry of Chardonnay marc, still much of the fundamental aroma chemistry is unknown. This includes potential changes in aroma chemistry that occur during processing such as postharvest handing, drying, milling, and storage. Additional knowledge gaps in the aroma chemistry of Chardonnay marc include agronomic factors such as the potential variation in growth conditions, location, and vintage, highlight areas for future investigations. Even less is known about the taste and chemosensory-active molecules present in Chardonnay marc. Taste and chemosensory-active compounds are generally isolated on the basis of a sensory-directed fractionation focused upon sensory evaluation of fractionated materials. Recently, sensory-directed fractionation of food extracts via chromatographic separations, sensory evaluation, and structural elucidation has led to the discovery of various novel taste and chemosensory-active molecules in foods, including black tea, morel mushrooms, red wine, Swiss cheese, Gouda cheese, cooked crab, and stewed beef. (157−162) Although the overall process of sensory-guided fractionation (for taste and chemosensory-active molecules) is similar to the process of identifying aroma active compounds in foods, a single methodology does not exist due to the diversity of the chemistry of the molecules. As a result, fractionation schemes are tailored in a case-by-case manner, primarily because these compounds tend to be nonvolatile in nature and structurally diverse. Broadly, a general approach is taken to identify taste and chemosensory-active compounds in foods; however, depending on the chemistry of the molecules, different sequences of separation techniques and analytical methods are employed.
So far, there have not been any studies published on the taste or chemosensory-active molecules present in Chardonnay marc. However, some known tastants and chemosensory-active molecules have been reported from grapes, including from Chardonnay. These include the sour tasting organic acids (i.e., succinic, malic, citric, and tartaric acid), (147,163) the bitter flavan-3-ols and procyanidins, (38,39,43,164−168) and velvety astringent flavanol glycosides (i.e., quercetin-3-O-α-d-glucopyranoside) (38,165,166) (Figure 4). In addition, amino acids and sugars with known taste activities have been reported. (169,170) Although, there have been no systematic studies reported on the taste chemistry of Chardonnay marc, based on the unique sensory attributes that it imparts to foods, along with its unique combination of potentially health promoting molecules, Chardonnay marc is a promising source of sensory-active molecules. Additional investigations are clearly warranted to determine the entire suite of sensory-active molecules (odorants, tastants, and chemosensory-active molecules) that contribute to a pleasant eating experience of foods and beverages containing Chardonnay marc. Accordingly, Chardonnay marc is an emerging healthy and flavorful food ingredient that demands further flavor chemistry research.

Figure 4

Figure 4. A few selected examples of tastants and chemosensory-active compounds identified in Chardonnay. Tartaric acid is a sour tasting organic acid. The monomeric flavan-3-ols, (+)catechin and (−)epicatechin, and the oligomeric procyanidins are bitter and astringency eliciting compounds. Quercetin-3-O-α-d-glucopyranoside elicits a velvety astringent sensory sensation.

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As dietary recommendations increasingly focus on foods and beverages providing a diverse array of PBNPs, new opportunities for precision health will need to consider both the isolated and interactive effects of these dietary components within any dietary pattern. In parallel, foods and beverages containing PBNPs required to improve public health and enable precision health strategies will need to delight consumers from a sensory perspective. This may include the utilization of upcycled ingredients in foods and beverages that enable a circular bioeconomy, yet can contribute significantly to improving public health and environmental sustainability. For the latter, a scale of market penetration is required in order to drive the use of upcycled ingredients containing PBNPs to volumes sufficient to impact environmental sustainability measures.
Chardonnay marc represents a highly desirable model for development of new upcycled ingredients having PBNP profiles that deliver a combination of health and sensory benefits envisioned to be in high demand from food manufacturers, as they do not require significant additional investments in research and development associated with flavor masking, extraction and fractionation, etc. Recent research focusing on Chardonnay marc has provided additional information regarding the natural products chemistry composition for a wide variety of health and sensory benefits when this marc is included in food and beverage products. Further research is warranted regarding a more detailed understanding of Chardonnay marc and the opportunity it represents as a new model for upcycled ingredients relevant to inclusion in food and beverage products.
To that end, computational data-driven methods have the potential to accelerate research and advance our understanding of how PBNPs affect human health, their mechanism of action, and their optimal processing and integration in our diets. Differential pathway analysis in both preclinical and clinical studies shed light on the differential expression and representation of genes and microbes, hence associating specific genes and taxa to health states and outcomes. Genome-wide models that incorporate metabolic reconstructions, protein–protein interactions, and regulatory networks can provide both mechanistic insights and an in-silico testbed on how dietary changes can modulate microbiota and the availability of metabolic compounds. Machine Learning and Artificial Intelligence can assist in optimizing the production of ingredients that have optimal balance of phenolic content, maximizing the retention and availability of these compounds while processing. Specialized machine learning areas, such as reinforcement learning, can be then applied to create true recommendation systems for the manufacturing of those ingredients and products that can target with higher precision specific health conditions in a synergic and combinatorial manner and hence improve human health in unprecedented ways. Chardonnay marc can be a key resource toward this vision, acting as a model for accelerating innovation converting other byproducts containing PBNPs into upcycled co-products sought after as value added ingredients for use throughout the global food and beverage industry.

Author Information

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  • Corresponding Author
  • Authors
    • Daniela Barile - Department of Food Science and Technology, University of California, Davis, Davis, California 95616, United States;  Orcidhttps://orcid.org/0000-0002-3889-1596
    • Selina C. Wang - Department of Food Science and Technology, University of California, Davis, Davis, California 95616, United States;  Orcidhttps://orcid.org/0000-0002-9030-837X
    • John P. Munafo - Department of Food Science, University of Tennessee, Knoxville, Tennessee 37996, United States;  Orcidhttps://orcid.org/0000-0003-4702-2955
    • Torey Arvik - Sonomaceuticals, LLC, Santa Rosa, California 95403, United States
    • Xueqi Li - Department of Food Science and Technology, University of California, Davis, Davis, California 95616, United States;  Orcidhttps://orcid.org/0000-0002-5400-1813
    • Fanny Lee - Sonomaceuticals, LLC, Santa Rosa, California 95403, United States;  Orcidhttps://orcid.org/0000-0002-7566-9353
    • Carl L. Keen - Department of Nutrition, University of California, Davis, Davis, California 95616, United States;  Orcidhttps://orcid.org/0000-0001-6602-4417
    • Ilias Tagkopoulos - Department of Computer Science and Genome Center, USDA/NSF AI Institute for Next Generation Food Systems (AIFS), University of California, Davis, Davis, California 95616 United States;  PIPA, LLC, Davis, California 95616, United States;  Orcidhttps://orcid.org/0000-0003-1104-7616
    • Harold H. Schmitz - March Capital US, LLC, Davis, California 95616, United States;  T.O.P., LLC, Davis, California 95616, United States;  Graduate School of Management, University of California, Davis, Davis, California 95616, United States;  Orcidhttps://orcid.org/0000-0001-9066-8968
  • Notes
    The authors declare the following competing financial interest(s): The following researchers have received research support from Sonomaceuticals, LLC: RRH and CLK (grant #A22-2323), DB (grant #A22-2313), SCW and XL (grant # A21-1888 and A22-2195), JPM Jr., and IT. FL and TA are employees of Sonomaceuticals LLC. HHS serves as a Sonomaceuticals LLC scientific advisor.

Acknowledgments

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This work was supported by Sonomaceuticals LLC.

References

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    A review. Food processing sustainability, as well as waste minimization, are key concerns for the modern food industry. A significant amt. of waste is generated by the fruit juice industry each year. In addn. to the economic losses caused by the removal of these wastes, its impact on the environment is undeniable. Therefore, researchers have focused on recovering the bioactive components from fruit juice processing, in which a great no. of phytochems. still exist in the agro-industrial wastes, to help minimize the waste burden as well as provide new sources of bioactive compds., which are believed to be protective agents against certain diseases such as cardiovascular diseases, cancer, and diabetes. Although these wastes contain non-negligible amts. of bioactive compds., information on the utilization of these byproducts in functional ingredient/food prodn. and their impact on the sensory quality of food products is still scarce. In this regard, this review summarizes the most recent literature on bioactive compds. present in the wastes of apple, citrus fruits, berries, stoned fruits, melons, and tropical fruit juices, together with their extn. techniques and valorization approaches. Besides, on the one hand, examples of different current food applications with the use of these wastes are provided. On the other hand, the challenges with respect to economic, sensory, and safety issues are also discussed.
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    Katekhaye, S. D.; Kamble, B.; Advankar, A.; Athwale, N.; Kulkarni, A.; Ghagare, A. Taste-Masking Techniques in Nutraceutical and Functional Food Industry. Flavors for Nutraceutical and Functional Foods; CRC Press: 2018; pp 123– 144.
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    Despoudi, S.; Bucatariu, C.; Otles, S.; Kartal, C.; Otles, S.; Despoudi, S.; Bucatariu, C.; Kartal, C. Food waste management, valorization, and sustainability in the food industry. In Food Waste Recovery, 2nd ed.; Galanakis, C. M., Ed.; Academic Press: San Diego, 2021; Chapter 1, pp 3– 19.
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    California Grape Crush; California Department of Food and Agriculture: Sacramento, CA, 2022; p 158.
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    Sweet, N. Chardonnay History and Selections at FPS; University of California, Davis: Davis, CA, 2007; p 36.
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    Bowers, J.; Boursiquot, J. M.; This, P.; Chu, K.; Johansson, H.; Meredith, C. Historical Genetics: The Parentage of Chardonnay, Gamay, and Other Wine Grapes of Northeastern France. Science 1999, 285 (5433), 1562– 1565,  DOI: 10.1126/science.285.5433.1562
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    Historical genetics: the parentage of Chardonnay, Gamay, and other wine grapes of Northeastern France
    Bowers, John; Boursiquot, Jean-Michel; This, Patrice; Chu, Kieu; Johansson, Henrik; Meredith, Carole
    Science (Washington, D. C.) (1999), 285 (5433), 1562-1565CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)
    The origins of the classic European wine grapes (Vitis vinifera) have been the subject of much speculation. In a search for parental relationships, microsatellite loci were analyzed in more than 300 grape cultivars. Sixteen wine grapes that have long been grown in northeastern France, including 'Chardonnay', 'Gamay noir', 'Aligote', and 'Melon', have microsatellite genotypes consistent with their being the progeny of a single pair of parents, 'Pinot' and 'Gouais blanc', both of which were widespread in this region in the Middle Ages. Parentage anal. at 32 microsatellite loci provides statistical support for these relationships,.
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    Crespan, M.; Migliaro, D.; Larger, S.; Pindo, M.; Petrussi, C.; Stocco, M.; Rusjan, D.; Sivilotti, P.; Velasco, R.; Maul, E. Unraveling the genetic origin of ‘Glera’, ‘Ribolla Gialla’ and other autochthonous grapevine varieties from Friuli Venezia Giulia (northeastern Italy). Sci. Rep 2020, 10 (1), 7206,  DOI: 10.1038/s41598-020-64061-w
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    Unraveling the genetic origin of 'Glera', 'Ribolla Gialla' and other autochthonous grapevine varieties from Friuli Venezia Giulia (northeastern Italy)
    Crespan, Manna; Migliaro, Daniele; Larger, Simone; Pindo, Massimo; Petrussi, Carlo; Stocco, Marco; Rusjan, Denis; Sivilotti, Paolo; Velasco, Riccardo; Maul, Erika
    Scientific Reports (2020), 10 (1), 7206CODEN: SRCEC3; ISSN:2045-2322. (Nature Research)
    Abstr.: 'Glera' and 'Ribolla Gialla' are the most economically relevant local grapevine cultivars of Friuli Venezia Giulia region (north-eastern Italy). 'Glera' is used to produce the world-renowned Prosecco wine. 'Ribolla Gialla' cultivation is constantly increasing due to the strong demand for sparkling wine and is the most important variety in Brda (Slovenia). Knowledge of local varieties history in terms of migration and pedigree relationships has scientific and marketing appeal. Following prospections, genotyping and ampelog. characterization of minor germplasm in Friuli Venezia Giulia, a further research was developed to understand the parentage relationships among the grapevine varieties grown in this region. An integrated strategy was followed combining the anal. of nuclear and chloroplast microsatellites with the Vitis 18k SNP chip. Two main recurrent parents were found, which can be regarded as "founders": 'Vulpea', an Austrian variety parent-offspring related with at least ten Friuli Venezia Giulia cultivars, among them 'Glera', and 'Refosco Nostrano', first degree related with other six Friuli Venezia Giulia varieties. 'Ribolla Gialla' was shown to be another member of the impressively long list of offspring derived from the prolific 'Heunisch Weiss'. Combining mol. markers and historical refs. was a high-performance strategy for retracing and adjusting the history of cultivars.
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    Roach, M. J.; Johnson, D. L.; Bohlmann, J.; van Vuuren, H. J. J.; Jones, S. J. M.; Pretorius, I. S.; Schmidt, S. A.; Borneman, A. R. Population sequencing reveals clonal diversity and ancestral inbreeding in the grapevine cultivar Chardonnay. PLoS Genet 2018, 14 (11), e1007807,  DOI: 10.1371/journal.pgen.1007807
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    Population sequencing reveals clonal diversity and ancestral inbreeding in the grapevine cultivar Chardonnay
    Roach, Michael J.; Johnson, Daniel L.; Bohlmann, Joerg; van Vuuren, Hennie J. J.; Jones, Steven J. M.; Pretorius, Isak S.; Schmidt, Simon A.; Borneman, Anthony R.
    PLoS Genetics (2018), 14 (11), e1007807/1-e1007807/24CODEN: PGLEB5; ISSN:1553-7404. (Public Library of Science)
    Chardonnay is the basis of some of the world's most iconic wines and its success is underpinned by a historic program of clonal selection. There are numerous clones of Chardonnay available that exhibit differences in key viticultural and oenol. traits that have arisen from the accumulation of somatic mutations during centuries of asexual propagation. However, the genetic variation that underlies these differences remains largely unknown. To address this knowledge gap, a high-quality, diploid-phased Chardonnay genome assembly was produced from single-mol. real time sequencing, and combined with re-sequencing data from 15 different Chardonnay clones. There were 1620 markers identified that distinguish the 15 clones. These markers were reliably used for clonal identification of independently sourced genomic material, as well as in identifying a potential genetic basis for some clonal phenotypic differences. The predicted parentage of the Chardonnay haplomes was elucidated by mapping sequence data from the predicted parents of Chardonnay (Gouais blanc and Pinot noir) against the Chardonnay ref. genome. This enabled the detection of instances of heterosis, with differentially-expanded gene families being inherited from the parents of Chardonnay. Most surprisingly however, the patterns of nucleotide variation present in the Chardonnay genome indicate that Pinot noir and Gouais blanc share an extremely high degree of kinship that has resulted in the Chardonnay genome displaying characteristics that are indicative of inbreeding.
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    Zulj Mihaljevic, M.; Maletic, E.; Preiner, D.; Zdunic, G.; Bubola, M.; Zyprian, E.; Pejic, I. Genetic Diversity, Population Structure, and Parentage Analysis of Croatian Grapevine Germplasm. Genes (Basel) 2020, 11 (7), 737,  DOI: 10.3390/genes11070737
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    Hunt, H. V.; Lawes, M. C.; Bower, M. A.; Haeger, J. W.; Howe, C. J. A banned variety was the mother of several major wine grapes. Biol. Lett. 2010, 6 (3), 367– 9,  DOI: 10.1098/rsbl.2009.0810
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    A banned variety was the mother of several major wine grapes
    Hunt, Harriet V.; Lawes, Matthew C.; Bower, Mim A.; Haeger, John W.; Howe, Christopher J.
    Biology Letters (London, United Kingdom) (2010), 6 (3), 367-369CODEN: BLLUAZ; ISSN:1744-9561. (Royal Society)
    A no. of widely grown varieties of Vitis vinifera ssp. sativa, the grape used for wine prodn., are known to have resulted from crosses between Pinot noir and Gouais blanc, although it is not known which was the maternal parent in these crosses. We have analyzed microsatellites and a single nucleotide polymorphism (SNP) in chloroplast DNA from these two varieties and twelve progeny strains, including Chardonnay, Gamay noir and Aligote. The results demonstrate that Gouais blanc was the maternal parent for nine of these strains, including Chardonnay, Gamay noir and Aligote. This is a striking conclusion, as Gouais is generally considered a highly inferior variety, and its cultivation was banned for many years in parts of Europe.
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    Dávila, I.; Robles, E.; Egüés, I.; Labidi, J.; Gullón, P. The Biorefinery Concept for the Industrial Valorization of Grape Processing By-Products. In Handbook of Grape Processing By-Products; Galanakis, C. M., Ed.; Academic Press: 2017; Chapter 2, pp 29– 53.
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    Kandylis, P.; Dimitrellou, D.; Moschakis, T. Recent applications of grapes and their derivatives in dairy products. Trends Food Sci. Tech 2021, 114, 696– 711,  DOI: 10.1016/j.tifs.2021.05.029
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    Recent applications of grapes and their derivatives in dairy products
    Kandylis, Panagiotis; Dimitrellou, Dimitra; Moschakis, Thomas
    Trends in Food Science & Technology (2021), 114 (), 696-711CODEN: TFTEEH; ISSN:0924-2244. (Elsevier Ltd.)
    Grapes are cultivated all over the world, esp. for winemaking, producing high quantities of byproducts like grape pomace. These grape processing byproducts contain large amts. of compds. with functional characteristics. In recent years, there has been a growing consumers' interest for functional foods, with dairy products leading in this field. Constituents inherent to grapes, derived from grape-based byproducts, have the potential to improve the functional properties of dairy products and to reduce the environmental pollution. In this review, the recent advances in the field of grapes, their derivs., and particularly grape pomace added to dairy products are summarized. The main effect on the physicochem., functional and sensory characteristics of dairy products like yogurt, cheese, fermented milk and ice cream are discussed. In addn., the review highlights the effect of grape compds. on starter and probiotic culture survival and on the intestinal microbiota. The large no. of possible applications concerning grapes and their derivs. in the dairy industry show their high revalorization potential. Several recent studies are available, describing the incorporation in different dairy products. Particular attention is needed concerning the possible neg. effects of their addn. on the acidity of the dairy products and their overall sensorial characteristics. Therefore, more studies are needed to isolate the appropriate grape byproduct characteristics, to evaluate their interaction with dairy constituents, and to optimize their level of addn. The main pos. effect is the substantial increase in total phenolic content and antioxidant activity, which are not present in dairy products. Finally, more studies are required to evaluate the synergetic effect of grape compds. and probiotics in dairy products and to examine the potential health benefits after their consumption.
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    Olejar, K. J.; Ricci, A.; Swift, S.; Zujovic, Z.; Gordon, K. C.; Fedrizzi, B.; Versari, A.; Kilmartin, P. A. Characterization of an Antioxidant and Antimicrobial Extract from Cool Climate. White Grape Marc. Antioxidants 2019, 8 (7), 232,  DOI: 10.3390/antiox8070232
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    Luchian, C. E.; Cotea, V. V.; Vlase, L.; Toiu, A. M.; Colibaba, L. C.; Răschip, I. E.; Nadăş, G.; Gheldiu, A. M.; Tuchiluş, C.; Rotaru, L. J. B. W. C. Antioxidant and antimicrobial effects of grape pomace extracts. Bio Web Conf. 2019, 15, 04006  DOI: 10.1051/bioconf/20191504006
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    Martins Flores, D. R.; Patricia da Fonseca, A. F.; Schmitt, J.; Jose Tonetto, C.; Rosado Junior, A. G.; Hammerschmitt, R. K.; Facco, D. B.; Brunetto, G.; Nornberg, J. L. Lambs fed with increasing levels of grape pomace silage: Effects on meat quality. Small Ruminant Res. 2021, 195, 106234,  DOI: 10.1016/j.smallrumres.2020.106234
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    Kasapidou, E.; Sossidou, E.; Mitlianga, P. Fruit and Vegetable Co-Products as Functional Feed Ingredients in Farm Animal Nutrition for Improved Product Quality. Agriculture-Basel 2015, 5 (4), 1020– 1034,  DOI: 10.3390/agriculture5041020
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    Fruit and vegetable co-products as functional feed ingredients in farm animal nutrition for improved product quality
    Kasapidou, Eleni; Sossidou, Evangelia; Mitlianga, Paraskevi
    Agriculture (Basel, Switzerland) (2015), 5 (4), 1020-1034CODEN: ABSGFK; ISSN:2077-0472. (MDPI AG)
    There are significant environmental, economic and social factors favoring the reutilization of fruit and vegetable processing co-products in farm animal nutrition. Current evidence shows that fruit and vegetable processing co-products can be effectively used in farm animal nutrition as functional feed ingredients for the prodn. of food products of improved quality. These ingredients comply with consumer requests for the prodn. of ''clean,'' ''natural'' and ''eco/green'' label food products. The main parameters affecting extensive application of fruit and vegetable processing by-/co-products as functional feed ingredients in livestock nutrition are related to animal factors, logistics, and com. value. Further research is needed to enable the com. application of these products to livestock nutrition.
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    Tayengwa, T.; Chikwanha, O. C.; Neethling, J.; Dugan, M. E. R.; Mutsvangwa, T.; Mapiye, C. Polyunsaturated fatty acid, volatile and sensory profiles of beef from steers fed citrus pulp or grape pomace. Food Res. Int. 2021, 139, 109923,  DOI: 10.1016/j.foodres.2020.109923
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    Polyunsaturated fatty acid, volatile and sensory profiles of beef from steers fed citrus pulp or grape pomace
    Tayengwa, Tawanda; Chikwanha, Obert C.; Neethling, Jeannine; Dugan, Michael E. R.; Mutsvangwa, Timothy; Mapiye, Cletos
    Food Research International (2021), 139 (), 109923CODEN: FORIEU; ISSN:0963-9969. (Elsevier B.V.)
    The present study compared the effects of feeding dried grape pomace (DGP) or citrus pulp (DCP) at 150 g/kg dry matter compared to a control diet on major polyunsatd. fatty acids (PUFA), volatile and sensory profiles of beef. Feeding DGP or DCP diets to Angus steers for 90 d increased the proportions of C18:2n-6, C20:4n-6, C18:3n-3, total conjugated linoleic acid (CLA), n-3 and n-6 PUFA in muscle. Control-fed beef had greater concns. of C18:1n-9, total aldehydes, ketones, and alcs. compared to DCP and DGP. Feeding DGP and DCP diets produced less tender beef than control. Overall, finishing steers on diets contg. DGP or DCP compared to control increased proportions of total CLA, n-3 and n-6 PUFA, and reduced concns. of aldehydes, ketones, and alcs., but did not affect beef sensory attributes except for a slight redn. in tenderness.
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    Garcia-Lomillo, J.; Gonzalez-SanJose, M. L. Applications of Wine Pomace in the Food Industry: Approaches and Functions. Compr Rev. Food Sci. Food Saf 2017, 16 (1), 3– 22,  DOI: 10.1111/1541-4337.12238
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    Applications of Wine Pomace in the Food Industry: Approaches and Functions
    Garcia-Lomillo, Javier; Gonzalez-SanJose, Maria Luisa
    Comprehensive Reviews in Food Science and Food Safety (2017), 16 (1), 3-22CODEN: CRFSBJ; ISSN:1541-4337. (Institute of Food Technologists)
    A review. Winemaking generates large amts. of wine pomace, also called grape pomace. This byproduct has attracted the attention of food scientists and the food industry, due to its high content in nutrients and bioactive compds. This review mainly focuses on the different published approaches to the use of wine pomace and its functions in the food industry. Traditionally, wine pomace has been used to obtain wine alc., food colorings, and grape seed oil. More recently, research has focused in the prodn. of other value-added products, such as exts. of bioactive compds., mainly phenols, recovery of tartaric acid, and the making of flours. The most common functions assocd. with wine pomace products are their use as antioxidants, followed by their use as fortifying, coloring, and antimicrobial agents. These products have mainly been applied to the prepn. of meat and fish products and to, a lesser extent, cereal products.
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    Arfaoui, L. Dietary Plant Polyphenols: Effects of Food Processing on Their Content and Bioavailability. Molecules 2021, 26 (10), 2959,  DOI: 10.3390/molecules26102959
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    Dietary plant polyphenols: effects of food processing on their content and bioavailability
    Arfaoui, Leila
    Molecules (2021), 26 (10), 2959CODEN: MOLEFW; ISSN:1420-3049. (MDPI AG)
    A review. Dietary plant polyphenols are natural bioactive compds. that are increasingly attracting the attention of food scientists and nutritionists because of their nutraceutical properties. In fact, many studies have shown that polyphenol-rich diets have protective effects against most chronic diseases. However, these health benefits are strongly related to both polyphenol content and bioavailability, which in turn depend on their origin, food matrix, processing, digestion, and cellular metab. Although most fruits and vegetables are valuable sources of polyphenols, they are not usually consumed raw. Instead, they go through some processing steps, either industrially or domestically (e.g., cooling, heating, drying, fermn., etc.), that affect their content, bioaccessibility, and bioavailability. This review summarizes the status of knowledge on the possible (pos. or neg.) effects of commonly used food-processing techniques on phenolic compd. content and bioavailability in fruits and vegetables. These effects depend on the plant type and applied processing parameters (type, duration, media, and intensity). This review attempts to shed light on the importance of more comprehensive dietary guidelines that consider the recommendations of processing parameters to take full advantage of phenolic compds. toward healthier foods.
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    Corte-Real, J.; Archaimbault, A.; Schleeh, T.; Cocco, E.; Herrmann, M.; Guignard, C.; Hausman, J. F.; Iken, M.; Legay, S. Handling wine pomace: The importance of drying to preserve phenolic profile and antioxidant capacity for product valorization. J. Food Sci. 2021, 86 (3), 892– 900,  DOI: 10.1111/1750-3841.15652
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    Handling wine pomace: The importance of drying to preserve phenolic profile and antioxidant capacity for product valorization
    Corte-Real, Joana; Archaimbault, Axel; Schleeh, Thomas; Cocco, Emmanuelle; Herrmann, Markus; Guignard, Cedric; Hausman, Jean-Francois; Iken, Marcus; Legay, Sylvain
    Journal of Food Science (2021), 86 (3), 892-900CODEN: JFDSAZ; ISSN:0022-1147. (Wiley-Blackwell)
    Four different wine grape pomaces (GP) (Vitis vinifera) varieties, Auxerrois, Pinot Blanc, Gamay and Pinot Noir, and obtained from white, rose or red wine vinification, were considered for possible valorization in food supplement industry. Stabilization of GP by drying is paramount prior to further processing in the valorization chain, as GP might suffer spoilage over time. The objectives of this work were therefore to: evaluate the effect of microbiol. spoilage and drying on the polyphenol profile and antioxidant capacity of GP; define a drying procedure by comparing kinetics of freeze-drying (FD) and vacuum oven (VO) (at 60°C and 40°C). Microbiol. spoilage led to significant losses (P < 0.01) of antioxidant capacity (40% to 87%) and total phenolic content (70% to 90%), while drying had no significant effect. FD and VO at 60°C drying kinetics exhibited similar drying curves, and a dry wt. (DW) plateau was reached by 48 h. In contrast VO at 40°C required 170 h to reach similar DW values, pointing out the importance of temp. when opting for VO technol. Antioxidant capacity of GP exts. did not differ between drying methods. Interestingly, GPs from white and rose wines (AUX, PB, and GAM) had up to 3.5 times higher content (P < 0.001) of total polyphenols compared to PN, obtained from red wine. These results reinforce the importance of drying of GP as a pretreatment, which otherwise could result in significant product degrdn. Addnl., we propose white and rose GP as more interesting sources for valorization, with higher phenolic content, compared to red wine GP.
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    Hollman, P. C. Unravelling of the health effects of polyphenols is a complex puzzle complicated by metabolism. Arch. Biochem. Biophys. 2014, 559, 100– 5,  DOI: 10.1016/j.abb.2014.04.013
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    Unravelling of the health effects of polyphenols is a complex puzzle complicated by metabolism
    Hollman, Peter C. H.
    Archives of Biochemistry and Biophysics (2014), 559 (), 100-105CODEN: ABBIA4; ISSN:0003-9861. (Elsevier B.V.)
    A review. Plant metab. creates complex mixts. of polyphenols in plant foods. Epidemiol. and human trials reduced this complexity, by studying specific foods; subclasses of polyphenols; individual polyphenols, or total antioxidant capacity (TAC). This implies the following assumptions: (1) a limited no. of potent polyphenols exists; (2) well-defined natural potent mixts. of polyphenols exist; (3) polyphenols share a common biol. activity (e.g. antioxidant activity). To find potent polyphenols (1st assumption), in vitro screening has been widely applied, but most published results are of limited use because metab., changing biol. activity profoundly, has frequently not been considered. The abundant anecdotal evidence for natural potent mixts. of polyphenols (2nd assumption) on the internet is very hard to verify. Addnl., cross-cultural studies have revealed the potency of e.g. cocoa. Polyphenols share the antioxidant phenolic group which inspired researchers to measure their antioxidant activity, thus greatly reducing complexity (3rd assumption). Unfortunately, the elegant antioxidant hypothesis has to be rejected, because poor absorption and extensive metab. annihilate any contribution to the endogenous body antioxidants. In conclusion, the above assumptions are hard to verify, and no quick answers are to be expected. Future research should focus on structure-activity relations at nanomolar levels and explore metabolomics.
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  28. 28
    Manela, N.; Oliva, M.; Ovadia, R.; Sikron-Persi, N.; Ayenew, B.; Fait, A.; Galili, G.; Perl, A.; Weiss, D.; Oren-Shamir, M. Phenylalanine and tyrosine levels are rate-limiting factors in production of health promoting metabolites in Vitis vinifera cv. Gamay Red cell suspension. Front Plant Sci. 2015, 6, 538,  DOI: 10.3389/fpls.2015.00538
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    28
    Phenylalanine and tyrosine levels are rate-limiting factors in production of health promoting metabolites in Vitis vinifera cv. Gamay Red cell suspension
    Manela Neta; Oliva Moran; Ovadia Rinat; Perl Avichai; Oren-Shamir Michal; Sikron-Persi Noga; Ayenew Biruk; Fait Aaron; Galili Gad; Weiss David
    Frontiers in plant science (2015), 6 (), 538 ISSN:1664-462X.
    Environmental stresses such as high light intensity and temperature cause induction of the shikimate pathway, aromatic amino acids (AAA) pathways, and of pathways downstream from AAAs. The induction leads to production of specialized metabolites that protect the cells from oxidative damage. The regulation of the diverse AAA derived pathways is still not well understood. To gain insight on that regulation, we increased AAA production in red grape Vitis vinifera cv. Gamay Red cell suspension, without inducing external stress on the cells, and characterized the metabolic effect of this induction. Increased AAA production was achieved by expressing a feedback-insensitive bacterial form of 3-deoxy- D-arabino-heptulosonate 7-phosphate synthase enzyme (AroG (*)) of the shikimate pathway under a constitutive promoter. The presence of AroG(*) protein led to elevated levels of primary metabolites in the shikimate and AAA pathways including phenylalanine and tyrosine, and to a dramatic increase in phenylpropanoids. The AroG (*) transformed lines accumulated up to 20 and 150 fold higher levels of resveratrol and dihydroquercetin, respectively. Quercetin, formed from dihydroquercetin, and resveratrol, are health promoting metabolites that are induced due to environmental stresses. Testing the expression level of key genes along the stilbenoids, benzenoids, and phenylpropanoid pathways showed that transcription was not affected by AroG (*). This suggests that concentrations of AAAs, and of phenylalanine in particular, are rate-limiting in production of these metabolites. In contrast, increased phenylalanine production did not lead to elevated concentrations of anthocyanins, even though they are also phenylpropanoid metabolites. This suggests a control mechanism of this pathway that is independent of AAA concentration. Interestingly, total anthocyanin concentrations were slightly lower in AroG(*) cells, and the relative frequencies of the different anthocyanins changed as well.
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    Fontana, A. R.; Antoniolli, A.; Bottini, R. Grape pomace as a sustainable source of bioactive compounds: extraction, characterization, and biotechnological applications of phenolics. J. Agric. Food Chem. 2013, 61 (38), 8987– 9003,  DOI: 10.1021/jf402586f
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    29
    Grape pomace as a sustainable source of bioactive compounds: extraction, characterization, and biotechnological applications of phenolics
    Fontana, Ariel R.; Antoniolli, Andrea; Bottini, Ruben
    Journal of Agricultural and Food Chemistry (2013), 61 (38), 8987-9003CODEN: JAFCAU; ISSN:0021-8561. (American Chemical Society)
    A review. Grape pomaces (GPs) are characterized by high contents of phenolics due to an incomplete extn. during the winemaking process. These phenolics are secondary plant metabolites with potential beneficial effects on human health because of their antioxidant activity and antimicrobial, antiviral, and anti-inflammatory properties. Therefore, GP constitutes an inexpensive source for the extn. of phytochems. that can be used in the pharmaceutical, cosmetic, and food industries. As a result of the increased attention to sustainability of agricultural practices, efforts have been made to use GP in different fields of industry. Thus, it is necessary to have efficient extn. techniques to achieve good recoveries of compds. In this respect, sensitive and selective anal. methods have been tried for the characterization of phenolic exts. This review summarizes the most recent developments in the extn. of polyphenols from GPs. Furthermore, the techniques used for characterization of exts. are explained, with emphasis on sample prepn., sepn., and anal. of phenolics. Finally, the possible applications of GP exts. in diverse biotechnol. fields are also discussed.
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    Emiliani, G.; Fondi, M.; Fani, R.; Gribaldo, S. A horizontal gene transfer at the origin of phenylpropanoid metabolism: a key adaptation of plants to land. Biology Direct 2009, 4 (1), 7,  DOI: 10.1186/1745-6150-4-7
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    A horizontal gene transfer at the origin of phenylpropanoid metabolism: a key adaptation of plants to land
    Emiliani Giovanni; Fondi Marco; Fani Renato; Gribaldo Simonetta
    Biology direct (2009), 4 (), 7 ISSN:.
    BACKGROUND: The pioneering ancestor of land plants that conquered terrestrial habitats around 500 million years ago had to face dramatic stresses including UV radiation, desiccation, and microbial attack. This drove a number of adaptations, among which the emergence of the phenylpropanoid pathway was crucial, leading to essential compounds such as flavonoids and lignin. However, the origin of this specific land plant secondary metabolism has not been clarified. RESULTS: We have performed an extensive analysis of the taxonomic distribution and phylogeny of Phenylalanine Ammonia Lyase (PAL), which catalyses the first and essential step of the general phenylpropanoid pathway, leading from phenylalanine to p-Coumaric acid and p-Coumaroyl-CoA, the entry points of the flavonoids and lignin routes. We obtained robust evidence that the ancestor of land plants acquired a PAL via horizontal gene transfer (HGT) during symbioses with soil bacteria and fungi that are known to have established very early during the first steps of land colonization. This horizontally acquired PAL represented then the basis for further development of the phenylpropanoid pathway and plant radiation on terrestrial environments. CONCLUSION: Our results highlight a possible crucial role of HGT from soil bacteria in the path leading to land colonization by plants and their subsequent evolution. The few functional characterizations of sediment/soil bacterial PAL (production of secondary metabolites with powerful antimicrobial activity or production of pigments) suggest that the initial advantage of this horizontally acquired PAL in the ancestor of land plants might have been either defense against an already developed microbial community and/or protection against UV.
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    Koch, W. Theaflavins, Thearubigins, and Theasinensins. In Handbook of Dietary Phytochemicals; Xiao, J., Sarker, S. D., Asakawa, Y., Eds.; Springer Singapore: Singapore, 2021; pp 975– 1003.
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    Holt, R. R.; Heiss, C.; Kelm, M.; Keen, C. L. The potential of flavanol and procyanidin intake to influence age-related vascular disease. J. Nutr Gerontol Geriatr 2012, 31 (3), 290– 323,  DOI: 10.1080/21551197.2012.702541
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    The potential of flavanol and procyanidin intake to influence age-related vascular disease
    Holt Roberta R; Heiss Christian; Kelm Malte; Keen Carl L
    Journal of nutrition in gerontology and geriatrics (2012), 31 (3), 290-323 ISSN:.
    Advancing age is an independent major risk factor for cardiovascular disease (CVD). Age-associated impairments in the control of inflammation, excessive oxidative stress, and reduced cellular repair can all contribute to the development and progression of CVD. Current recommendations for both the primary and secondary prevention of CVD promote lifestyle modifications that include the adoption of healthy dietary patterns, such as the consumption of diets rich in plant foods, as these have been associated with a lower lifetime risk for the development of CVD. The potential for a diet rich in plant foods to be cardiovascular protective is also supported by prospective studies that suggest the intake of foods providing high amounts of certain phytochemicals, in particular flavanols and procyanidins, reduce the risk for CVD. These observations are further supported by a number of dietary intervention trials that show improvements in vascular function and reduced platelet reactivity following the consumption of high flavanol foods. In the current article we review a selection of these studies, and comment on some of the potential mechanisms that have been postulated to underlie the health effects of flavanol and procyanidin-rich foods.
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    Ottaviani, J. I.; Momma, T. Y.; Kuhnle, G. K.; Keen, C. L.; Schroeter, H. Structurally related (−)-epicatechin metabolites in humans: assessment using de novo chemically synthesized authentic standards. Free Radic Biol. Med. 2012, 52 (8), 1403– 12,  DOI: 10.1016/j.freeradbiomed.2011.12.010
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    Structurally related (-)-epicatechin metabolites in humans: Assessment using de novo chemically synthesized authentic standards
    Ottaviani, Javier I.; Momma, Tony Y.; Kuhnle, Gunter K.; Keen, Carl L.; Schroeter, Hagen
    Free Radical Biology & Medicine (2012), 52 (8), 1403-1412CODEN: FRBMEH; ISSN:0891-5849. (Elsevier B.V.)
    Accumulating data suggest that diets rich in flavanols and procyanidins are beneficial for human health. In this context, there has been a great interest in elucidating the systemic levels and metabolic profiles at which these compds. occur in humans. Although recent progress has been made, there still exist considerable differences and various disagreements with regard to the mammalian metabolites of these compds., which in turn are largely a consequence of the lack of availability of authentic stds. that would allow for the directed development and validation of expedient anal. methodologies. In this study, we developed a method for the anal. of structurally related flavanol metabolites using a wide range of authentic stds. Applying this method in the context of a human dietary intervention study using comprehensively characterized and standardized flavanol- and procyanidin-contg. cocoa, we were able to identify the structurally related (-)-epicatechin metabolites (SREM) postprandially extant in the systemic circulation of humans. Our results demonstrate that (-)-epicatechin-3'-β-d-glucuronide, (-)-epicatechin-3'-sulfate, and a 3'-O-methyl-(-)-epicatechin-5/7-sulfate are the predominant SREM in humans and further confirm the relevance of the stereochem. configuration in the context of flavanol metab. In addn., we also identified plausible causes for the previously reported discrepancies regarding flavanol metab., consisting, to a significant extent, of interlab. differences in sample prepn. (enzymic treatment and sample conditioning for HPLC anal.) and detection systems. Thus, these findings may also aid in the establishment of consensus on this topic.
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    Liu, X.; Le Bourvellec, C.; Guyot, S.; Renard, C. Reactivity of flavanols: Their fate in physical food processing and recent advances in their analysis by depolymerization. Compr Rev. Food Sci. Food Saf 2021, 20 (5), 4841– 4880,  DOI: 10.1111/1541-4337.12797
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    Reactivity of flavanols: Their fate in physical food processing and recent advances in their analysis by depolymerization
    Liu, Xuwei; Le Bourvellec, Carine; Guyot, Sylvain; Renard, Catherine M. G. C.
    Comprehensive Reviews in Food Science and Food Safety (2021), 20 (5), 4841-4880CODEN: CRFSBJ; ISSN:1541-4337. (Institute of Food Technologists)
    A Review. Flavanols, a subgroup of polyphenols, are secondary metabolites with antioxidant properties naturally produced in various plants (e.g., green tea, cocoa, grapes, and apples); they are a major polyphenol class in human foods and beverages, and have recognized effect on maintaining human health. Therefore, it is necessary to evaluate their changes (i.e., oxidn., polymn., degrdn., and epimerization) during various phys. processing (i.e., heating, drying, mech. shearing, high-pressure, ultrasound, and radiation) to improve the nutritional value of food products. However, the roles of flavanols, in particular for their polymd. forms, are often underestimated, for a large part because of anal. challenges: they are difficult to ext. quant., and their quantification demands chem. reactions. This review examines the existing data on the effects of different phys. processing techniques on the content of flavanols and highlights the changes in epimerization and d.p., as well as some of the latest acidolysis methods for proanthocyanidin characterization and quantification. More and more evidence show that phys. processing can affect content but also modify the structure of flavanols by promoting a series of internal reactions. The most important reactivity of flavanols in processing includes oxidative coupling and rearrangements, chain cleavage, structural rearrangements (e.g., polymn., degrdn., and epimerization), and addn. to other macromols., i.e., proteins and polysaccharides. Some acidolysis methods for the anal. of polymeric proanthocyanidins have been updated, which has contributed to complete anal. of proanthocyanidin structures in particular regarding their proportion of A-type proanthocyanidins and their d.p. in various plants. However, future research is also needed to better ext. and characterize high-polymer proanthocyanidins, whether in their native or modified forms.
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    Machonis, P.; Jones, M.; Schaneberg, B.; Kwik-Uribe, C.; Dowell, D. Method for the determination of catechin and epicatechin enantiomers in cocoa-based ingredients and products by high-performance liquid chromatography: First Action 2013.04. J. AOAC Int. 2014, 97 (2), 506– 9,  DOI: 10.5740/jaoacint.13-351
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    Method for the determination of catechin and epicatechin enantiomers in cocoa-based ingredients and products by high-performance liquid chromatography: first action 2013.04
    Machonis, Philip; Jones, Matthew; Schaneberg, Brian; Kwik-Uribe, Catherine; Dowell, Dawn
    Journal of AOAC International (2014), 97 (2), 506-509CODEN: JAINEE; ISSN:1060-3271. (AOAC International)
    Single-lab. validation data previously published in the Journal of AOAC INTERNATIONAL 95(2), 500-507 (2012) was reviewed by the Stakeholder Panel on Strategic Food Anal. Methods Expert Review Panel (ERP) at the AOAC INTERNATIONAL Mid-Year Meeting held on March 12-14, 2013 in Rockville, MD. The ERP detd. the data presented met the established std. method performance requirement and approved the method as AOAC Official First Action on March 14, 2013. Using high-performance liq. chromatog. (HPLC), flavanol enantiomers, (+)- and (-)-epicatechin and (+)- and (-)-catechin, are eluted isocratically using ammonium acetate and methanol mobile phase. The mobile phase is applied to a modified β-cyclodextrin chiral stationary phase and the flavanols detected by fluorescence. Using several cocoa-based matrixes, recoveries for the four enantiomers ranged from 82.2-102.1% at a 50% spike level, and 80.4-101.1% at a 100% spike level. Precision was detd. to be 1.46-3.22% for (-)-epicatechin, 3.66-6.90% for (+)-catechin, 1.69-6.89% for (-)-catechin. (+)-Epicatechin was not detected in any of the samples used for this work, so precision could not be detd. for this mol.
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    Renaud, S.; de Lorgeril, M. Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet 1992, 339 (8808), 1523– 6,  DOI: 10.1016/0140-6736(92)91277-F
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    Wine, alcohol, platelets, and the French paradox for coronary heart disease
    Renaud S; de Lorgeril M
    Lancet (London, England) (1992), 339 (8808), 1523-6 ISSN:0140-6736.
    In most countries, high intake of saturated fat is positively related to high mortality from coronary heart disease (CHD). However, the situation in France is paradoxical in that there is high intake of saturated fat but low mortality from CHD. This paradox may be attributable in part to high wine consumption. Epidemiological studies indicate that consumption of alcohol at the level of intake in France (20-30 g per day) can reduce risk of CHD by at least 40%. Alcohol is believed to protect from CHD by preventing atherosclerosis through the action of high-density-lipoprotein cholesterol, but serum concentrations of this factor are no higher in France than in other countries. Re-examination of previous results suggests that, in the main, moderate alcohol intake does not prevent CHD through an effect on atherosclerosis, but rather through a haemostatic mechanism. Data from Caerphilly, Wales, show that platelet aggregation, which is related to CHD, is inhibited significantly by alcohol at levels of intake associated with reduced risk of CHD. Inhibition of platelet reactivity by wine (alcohol) may be one explanation for protection from CHD in France, since pilot studies have shown that platelet reactivity is lower in France than in Scotland.
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    Frankel, E. N.; Kanner, J.; German, J. B.; Parks, E.; Kinsella, J. E. Inhibition of oxidation of human low-density lipoprotein by phenolic substances in red wine. Lancet 1993, 341 (8843), 454– 7,  DOI: 10.1016/0140-6736(93)90206-V
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    Inhibition of oxidation of human low-density lipoprotein by phenolic substances in red wine
    Frankel, E. N.; Kanner, J.; German, J. B.; Parks, E.; Kinsella, J. E.
    Lancet (1993), 341 (8843), 454-7CODEN: LANCAO; ISSN:0140-6736.
    The French paradox (apparent compatibility of a high fat diet with a low incidence of coronary atherosclerosis) has been attributed to the regular drinking of red wine. However, the alc. content of wine may not be the sole explanation for this protection. Red wine also contains phenolic compds, and the antioxidant properties of these may have an important role. In vitro studies with phenolic substances in red wine and normal human low-d. lipoprotein (LDL) showed that red wine inhibits the copper catalyzed oxidn. of LDL. Wine dild. 1000-fold contg. 10 μmol/L total phenolics inhibited LDL oxidn. significantly more than did α-tocopherol.
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    Rodriguez Montealegre, R.; Romero Peces, R.; Chacon Vozmediano, J.L.; Martinez Gascuena, J.; Garcia Romero, E. Phenolic compounds in skins and seeds of ten grape Vitis vinifera varieties grown in a warm climate. Journal of Food Composition and Analysis 2006, 19, 687– 693,  DOI: 10.1016/j.jfca.2005.05.003
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    Phenolic compounds in skins and seeds of ten grape Vitis vinifera varieties grown in a warm climate
    Rodriguez Montealegre, R.; Romero Peces, R.; Chacon Vozmediano, J. L.; Martinez Gascuena, J.; Garcia Romero, E.
    Journal of Food Composition and Analysis (2006), 19 (6-7), 687-693CODEN: JFCAEE; ISSN:0889-1575. (Elsevier)
    This study employed high performance liq. chromatog. (HPLC) to analyze non-anthocyanin phenols present in the skins and seeds of 70 grape samples belonging to 10 cultivars. Grape skins contained tartaric esters of hydroxycinnamic acids (6-45 mg/kg of grape), monomeric and dimeric flavan-3-ols (9-96 mg/kg) and flavonols (25-197 mg/kg). The seed constituents comprised almost exclusively flavan-3-ols with concn. ranges of 330-1390 mg/kg. Certain varietal differences were obsd., although other important factors have to be taken into account such as the degree of ripeness or berry size. The differences with respect to the results reported by other authors in relation to relative concns. of procyanidins were attributable to climatic differences in the areas where the different studies were performed, in our case with very hot summers.
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    Yilmaz, Y.; Toledo, R. T. Major Flavonoids in Grape Seeds and Skins: Antioxidant Capacity of Catechin, Epicatechin, and Gallic Acid. J. Agric. Food Chem. 2004, 52 (2), 255– 260,  DOI: 10.1021/jf030117h
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    Major Flavonoids in Grape Seeds and Skins: Antioxidant Capacity of Catechin, Epicatechin, and Gallic Acid
    Yilmaz, Yusuf; Toledo, Romeo T.
    Journal of Agricultural and Food Chemistry (2004), 52 (2), 255-260CODEN: JAFCAU; ISSN:0021-8561. (American Chemical Society)
    Grape seeds and skins are good sources of phytochems. such as gallic acid, catechin, and epicatechin and are suitable raw materials for the prodn. of antioxidative dietary supplements. The differences in levels of the major monomeric flavanols and phenolic acids in seeds and skins from grapes of Vitis vinifera varieties Merlot and Chardonnay and in seeds from grapes of Vitis rotundifolia variety Muscadine were detd., and the antioxidant activities of these components were assessed. The contribution of the major monomeric flavonols and phenolic acid to the total antioxidant capacity of grape seeds and skins was also detd. Gallic acid, monomeric catechin, and epicatechin concns. were 99, 12, and 96 mg/100 g of dry matter (dm) in Muscadine seeds, 15, 358, and 421 mg/100 g of dm in Chardonnay seeds, and 10, 127, and 115 mg/100 g of dm in Merlot seeds, resp. Concns. of these 3 compds. were lower in winery byproduct grape skins than in seeds. These 3 major phenolic constituents of grape seeds contributed <26% to the antioxidant capacity measured as ORAC on the basis of the cor. concns. of gallic acid, catechin, and epicatechin in grape byproducts. Peroxyl radical scavenging activities of phenolics present in grape seeds or skins in decreasing order were resveratrol > catechin > epicatechin = gallocatechin > gallic acid = ellagic acid. Thus,t dimeric, trimeric, oligomeric, or polymeric procyanidins account for most of the superior antioxidant capacity of grape seeds.
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    Rodriguez-Mateos, A.; Weber, T.; Skene, S. S.; Ottaviani, J. I.; Crozier, A.; Kelm, M.; Schroeter, H.; Heiss, C. Assessing the respective contributions of dietary flavanol monomers and procyanidins in mediating cardiovascular effects in humans: randomized, controlled, double-masked intervention trial. Am. J. Clin. Nutr. 2018, 108 (6), 1229– 1237,  DOI: 10.1093/ajcn/nqy229
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    Assessing the respective contributions of dietary flavanol monomers and procyanidins in mediating cardiovascular effects in humans: randomized, controlled, double-masked intervention trial
    Rodriguez-Mateos Ana; Weber Timon; Kelm Malte; Heiss Christian; Skene Simon S; Heiss Christian; Ottaviani Javier I; Schroeter Hagen; Crozier Alan
    The American journal of clinical nutrition (2018), 108 (6), 1229-1237 ISSN:.
    Background: Flavanols are an important class of food bioactives that can improve vascular function even in healthy subjects. Cocoa flavanols (CFs) are composed principally of the monomer (-)-epicatechin (∼20%), with a degree of polymerisation (DP) of 1 (DP1), and oligomeric procyanidins (∼80%, DP2-10). Objective: Our objective was to investigate the relative contribution of procyanidins and (-)-epicatechin to CF intake-related improvements in vascular function in healthy volunteers. Design: In a randomized, controlled, double-masked, parallel-group dietary intervention trial, 45 healthy men (aged 18-35 y) consumed the following once daily for 1 mo: 1) a DP1-10 cocoa extract containing 130 mg (-)-epicatechin and 560 mg procyanidins, 2) a DP2-10 cocoa extract containing 20 mg (-)-epicatechin and 540 mg procyanidins, or 3) a control capsule, which was flavanol-free but had identical micro- and macronutrient composition. Results: Consumption of DP1-10, but not of either DP2-10 or the control capsule, significantly increased flow-mediated vasodilation (primary endpoint) and the concentration of structurally related (-)-epicatechin metabolites (SREMs) in the circulatory system while decreasing pulse wave velocity and blood pressure. Total cholesterol significantly decreased after daily intake of both DP1-10 and DP2-10 as compared with the control. Conclusions: CF-related improvements in vascular function are predominantly related to the intake of flavanol monomers and circulating SREMs in healthy humans but not to the more abundant procyanidins and gut microbiome-derived CF catabolites. Reduction in total cholesterol was linked to consumption of procyanidins but not necessarily to that of (-)-epicatechin. This trial was registered at clinicaltrials.gov as NCT02728466.
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    de la Cerda-Carrasco, A.; Lopez-Solis, R.; Nunez-Kalasic, H.; Pena-Neira, A.; Obreque-Slier, E. Phenolic composition and antioxidant capacity of pomaces from four grape varieties (Vitis vinifera L.). J. Sci. Food Agric 2015, 95 (7), 1521– 7,  DOI: 10.1002/jsfa.6856
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    Phenolic composition and antioxidant capacity of pomaces from four grape varieties (Vitis vinifera L.)
    de la Cerda-Carrasco, Aaron; Lopez-Solis, Remigio; Nunez-Kalasic, Hugo; Pena-Neira, Alvaro; Obreque-Slier, Elias
    Journal of the Science of Food and Agriculture (2015), 95 (7), 1521-1527CODEN: JSFAAE; ISSN:0022-5142. (John Wiley & Sons Ltd.)
    Phenolic compds. are widely distributed secondary metabolites in plants usually conferring them with unique taste, flavor and health-promoting properties. In fruits of Vitis vinifera L., phenolic compn. is highly dependent on grape variety. Differential extn. of these compds. from grapes during winemaking is critically assocd. with wine quality. Byproducts of winemaking, such as grape pomace, can contain significant amts. of polyphenols. However, information concerning the varietal effect on wine grape pomace is scarce. In this study, pomaces from Sauvignon Blanc (SB), Chardonnay (CH), Cabernet Sauvignon (CS) and Carmenere (CA) grape varieties were characterized spectroscopically and by HPLC-DAD anal. White grape pomaces (SB and CH) presented higher antioxidant capacities and higher contents of total phenols and total proanthocyanidins compared with red grape pomaces (CS and CA), whereas the latter showed much higher anthocyanin levels and color intensities. Concns. of monomeric proanthocyanidins and low-mol.-wt. phenols in the four grape pomace varieties were significantly different. Grape pomaces from four varieties showed high but diverse contents of polyphenols and antioxidant capacities. Thus grape pomaces represent an important potential source of polyphenols, which could be useful for nutritional and/or pharmacol. purposes. © 2014 Society of Chem. Industry.
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    Kammerer, D.; Claus, A.; Carle, R.; Schieber, A. Polyphenol screening of pomace from red and white grape varieties (Vitis vinifera L.) by HPLC-DAD-MS/MS. J. Agric. Food Chem. 2004, 52 (14), 4360– 7,  DOI: 10.1021/jf049613b
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    Polyphenol Screening of Pomace from Red and White Grape Varieties (Vitis vinifera L.) by HPLC-DAD-MS/MS
    Kammerer, Dietmar; Claus, Achim; Carle, Reinhold; Schieber, Andreas
    Journal of Agricultural and Food Chemistry (2004), 52 (14), 4360-4367CODEN: JAFCAU; ISSN:0021-8561. (American Chemical Society)
    Phenolic compds. of 14 pomace samples originating from red and white winemaking were characterized by HPLC-MS. Up to 13 anthocyanins, 11 hydroxybenzoic and hydroxycinnamic acids, and 13 catechins and flavonols as well as 2 stilbenes were identified and quantified in the skins and seeds by HPLC-DAD. Large variabilities comprising all individual phenolic compds. were obsd., depending on cultivar and vintage. Grape skins proved to be rich sources of anthocyanins, hydroxycinnamic acids, flavanols, and flavonol glycosides, whereas flavanols were mainly present in the seeds. However, besides the lack of anthocyanins in white grape pomace, no principal differences between red and white grape varieties were obsd. This is the first study presenting comprehensive data on the contents of individual phenolic compds. comprising all polyphenolic subclasses of grapes including a comparison of several red and white pomaces from nine cultivars. The results obtained in the present study confirm that both skins and seeds of most grape cultivars constitute a promising source of polyphenolics.
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    Sinrod, A. J. G.; Li, X.; Bhattacharya, M.; Paviani, B.; Wang, S. C.; Barile, D. A second life for wine grapes: Discovering potentially bioactive oligosaccharides and phenolics in chardonnay marc and its processing fractions. LWT 2021, 144, 111192,  DOI: 10.1016/j.lwt.2021.111192
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    A second life for wine grapes: Discovering potentially bioactive oligosaccharides and phenolics in chardonnay marc and its processing fractions
    Sinrod, Amanda J. G.; Li, Xueqi; Bhattacharya, Mrittika; Paviani, Bruna; Wang, Selina C.; Barile, Daniela
    LWT--Food Science and Technology (2021), 144 (), 111192CODEN: LSTWB3; ISSN:0023-6438. (Elsevier Ltd.)
    Chardonnay marc (pomace), an agricultural waste product, has demonstrated significant potential health benefits in previous studies. This study represents the first comprehensive chem. characterization of chardonnay marc, its seed and seedless fractions, and a seed ext. to uncover the bioactive compds. inducing their obsd. health benefits. Chardonnay marc and its processing fractions' gross compn. (i.e. protein, lignin, fat, carbohydrates, polysaccharides), phenolic contents, and oligosaccharide profiles were detd. The chardonnay seeds contained higher quantities of protein, fat, and polysaccharides than the seedless marc while the seedless marc contained more total carbohydrates and sugars. All samples had abundant phenolics with the seed ext. being the most concd. (34.72 ± 0.13 mg/g). (-)-Gallocatechin was the most abundant phenolic in the marc (1.4905 ± 0.0393 mg/g) and seedless marc (0.94 ± 0.04 mg/g), and (-)-epicatechin was the most concd. phenolic in the seeds (9.4093 ± 0.1018 mg/g) and seed ext. (14.22 ± 0.09 mg/g). Thirty-six distinct oligosaccharides were discovered between the four samples with three to nine ds.p. and eleven distinct monosaccharide subunits. Overlap existed between the samples' oligosaccharides with six of the same hexose and hexose-pentose oligosaccharides present in all. Each sample, however, had a distinct oligosaccharide profile such as with eight oligosaccharides unique to the seed ext.
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    Fahey, G. C., Jr.; Jung, H. G. Lignin as a Marker in Digestion Studies: a Review. Journal of Animal Science 1983, 57 (1), 220– 225,  DOI: 10.2527/jas1983.571220x
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    Lignin as a marker in digestion studies: a review
    Fahey, G. C., Jr.; Jung, H. G.
    Journal of Animal Science (Savoy, IL, United States) (1983), 57 (1), 220-5CODEN: JANSAG; ISSN:0021-8812.
    A review with 51 refs. on problems which arise when lignin [9005-53-2] is used as a digestion study marker. Esp. important are low fecal recoveries, inexact anal. techniques for lignin, and possibly modification or degrdn. of lignin by gastrointestinal microbes.
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    Johnson, I. T. Fiber. In Present Knowledge in Nutrition, 11th ed.; Marriott, B. P., Birt, D. F., Stallings, V. A., Yates, A. A., Eds.; Academic Press: 2020; pp 515– 529.
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    Dahl, W. J.; Stewart, M. L. Position of the Academy of Nutrition and Dietetics: Health Implications of Dietary Fiber. J. Acad. Nutr Diet 2015, 115 (11), 1861– 70,  DOI: 10.1016/j.jand.2015.09.003
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    Position of the Academy of Nutrition and Dietetics: Health Implications of Dietary Fiber
    Dahl Wendy J; Stewart Maria L
    Journal of the Academy of Nutrition and Dietetics (2015), 115 (11), 1861-70 ISSN:2212-2672.
    It is the position of the Academy of Nutrition and Dietetics that the public should consume adequate amounts of dietary fiber from a variety of plant foods. Dietary fiber is defined by the Institute of Medicine Food Nutrition Board as "nondigestible carbohydrates and lignin that are intrinsic and intact in plants." Populations that consume more dietary fiber have less chronic disease. Higher intakes of dietary fiber reduce the risk of developing several chronic diseases, including cardiovascular disease, type 2 diabetes, and some cancers, and have been associated with lower body weights. The Adequate Intake for fiber is 14 g total fiber per 1,000 kcal, or 25 g for adult women and 38 g for adult men, based on research demonstrating protection against coronary heart disease. Properties of dietary fiber, such as fermentability and viscosity, are thought to be important parameters influencing the risk of disease. Plant components associated with dietary fiber may also contribute to reduced disease risk. The mean intake of dietary fiber in the United States is 17 g/day with only 5% of the population meeting the Adequate Intake. Healthy adults and children can achieve adequate dietary fiber intakes by increasing their intake of plant foods while concurrently decreasing energy from foods high in added sugar and fat, and low in fiber. Dietary messages to increase consumption of whole grains, legumes, vegetables, fruits, and nuts should be broadly supported by food and nutrition practitioners.
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    Koh, A.; De Vadder, F.; Kovatcheva-Datchary, P.; Bäckhed, F. From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites. Cell 2016, 165 (6), 1332– 1345,  DOI: 10.1016/j.cell.2016.05.041
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    From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites
    Koh, Ara; De Vadder, Filipe; Kovatcheva-Datchary, Petia; Baeckhed, Fredrik
    Cell (Cambridge, MA, United States) (2016), 165 (6), 1332-1345CODEN: CELLB5; ISSN:0092-8674. (Cell Press)
    A review. A compelling set of links between the compn. of the gut microbiota, the host diet, and host physiol. has emerged. Do these links reflect cause-and-effect relationships, and what might be their mechanistic basis. A growing body of work implicates microbially produced metabolites as crucial executors of diet-based microbial influence on the host. Here, we will review data supporting the diverse functional roles carried out by a major class of bacterial metabolites, the short-chain fatty acids (SCFAs). SCFAs can directly activate G-coupled-receptors, inhibit histone deacetylases, and serve as energy substrates. They thus affect various physiol. processes and may contribute to health and disease.
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    Dallas, D. C.; Sanctuary, M. R.; Qu, Y.; Khajavi, S. H.; Van Zandt, A. E.; Dyandra, M.; Frese, S. A.; Barile, D.; German, J. B. Personalizing protein nourishment. Critical Reviews in Food Science and Nutrition 2017, 57 (15), 3313– 3331,  DOI: 10.1080/10408398.2015.1117412
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    Personalizing protein nourishment
    Dallas, David C.; Sanctuary, Megan R.; Qu, Yunyao; Khajavi, Shabnam Haghighat; Van Zandt, Alexandria E.; Dyandra, Melissa; Frese, Steven A.; Barile, Daniela; German, J. Bruce
    Critical Reviews in Food Science and Nutrition (2017), 57 (15), 3313-3331CODEN: CRFND6; ISSN:1040-8398. (Taylor & Francis, Inc.)
    A review. Proteins are not equally digestible-their proteolytic susceptibility varies by their source and processing method. Incomplete digestion increases colonic microbial protein fermn. (putrefaction), which produces toxic metabolites that can induce inflammation in vitro and have been assocd. with inflammation in vivo. Individual humans differ in protein digestive capacity based on phenotypes, particularly disease states. To avoid putrefaction-induced intestinal inflammation, protein sources, and processing methods must be tailored to the consumer's digestive capacity. This review explores how food processing techniques alter protein digestibility and examines how physiol. conditions alter digestive capacity. Possible solns. to improving digestive function or matching low digestive capacity with more digestible protein sources are explored. Beyond the ileal digestibility measurements of protein digestibility, less invasive, quicker and cheaper techniques for monitoring the extent of protein digestion and fermn. are needed to personalize protein nourishment. Biomarkers of protein digestive capacity and efficiency can be identified with the toolsets of peptidomics, metabolomics, microbial sequencing and multiplexed protein anal. of fecal and urine samples. By monitoring individual protein digestive function, the protein component of diets can be tailored via protein source and processing selection to match individual needs to minimize colonic putrefaction and, thus, optimize gut health.
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    Desai, M. S.; Seekatz, A. M.; Koropatkin, N. M.; Kamada, N.; Hickey, C. A.; Wolter, M.; Pudlo, N. A.; Kitamoto, S.; Terrapon, N.; Muller, A.; Young, V. B.; Henrissat, B.; Wilmes, P.; Stappenbeck, T. S.; Núñez, G.; Martens, E. C. A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility. Cell 2016, 167 (5), 1339– 1353,  DOI: 10.1016/j.cell.2016.10.043
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    A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility
    Desai, Mahesh S.; Seekatz, Anna M.; Koropatkin, Nicole M.; Kamada, Nobuhiko; Hickey, Christina A.; Wolter, Mathis; Pudlo, Nicholas A.; Kitamoto, Sho; Terrapon, Nicolas; Muller, Arnaud; Young, Vincent B.; Henrissat, Bernard; Wilmes, Paul; Stappenbeck, Thaddeus S.; Nunez, Gabriel; Martens, Eric C.
    Cell (Cambridge, MA, United States) (2016), 167 (5), 1339-1353.e21CODEN: CELLB5; ISSN:0092-8674. (Cell Press)
    Despite the accepted health benefits of consuming dietary fiber, little is known about the mechanisms by which fiber deprivation impacts the gut microbiota and alters disease risk. Using a gnotobiotic mouse model, in which animals were colonized with a synthetic human gut microbiota composed of fully sequenced commensal bacteria, we elucidated the functional interactions between dietary fiber, the gut microbiota, and the colonic mucus barrier, which serves as a primary defense against enteric pathogens. We show that during chronic or intermittent dietary fiber deficiency, the gut microbiota resorts to host-secreted mucus glycoproteins as a nutrient source, leading to erosion of the colonic mucus barrier. Dietary fiber deprivation, together with a fiber-deprived, mucus-eroding microbiota, promotes greater epithelial access and lethal colitis by the mucosal pathogen, Citrobacter rodentium. Our work reveals intricate pathways linking diet, the gut microbiome, and intestinal barrier dysfunction, which could be exploited to improve health using dietary therapeutics.
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    Gentile, C. L.; Weir, T. L. The gut microbiota at the intersection of diet and human health. Science 2018, 362 (6416), 776– 780,  DOI: 10.1126/science.aau5812
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    The gut microbiota at the intersection of diet and human health
    Gentile, Christopher L.; Weir, Tiffany L.
    Science (Washington, DC, United States) (2018), 362 (6416), 776-780CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)
    A review. Diet affects multiple facets of human health and is inextricably linked to chronic metabolic conditions such as obesity, type 2 diabetes, and cardiovascular disease. Dietary nutrients are essential not only for human health but also for the health and survival of the trillions of microbes that reside within the human intestines. Diet is a key component of the relationship between humans and their microbial residents; gut microbes use ingested nutrients for fundamental biol. processes, and the metabolic outputs of those processes may have important impacts on human physiol. Studies in humans and animal models are beginning to unravel the underpinnings of this relationship, and increasing evidence suggests that it may underlie some of the broader effects of diet on human health and disease.
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    Sjögren, Y. M.; Tomicic, S.; Lundberg, A.; Böttcher, M. F.; Björkstén, B.; Sverremark-Ekström, E.; Jenmalm, M. C. Influence of early gut microbiota on the maturation of childhood mucosal and systemic immune responses. Clin. Exp. Allergy 2009, 39 (12), 1842– 1851,  DOI: 10.1111/j.1365-2222.2009.03326.x
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    Influence of early gut microbiota on the maturation of childhood mucosal and systemic immune responses
    Sjogren Y M; Tomicic S; Lundberg A; Bottcher M F; Bjorksten B; Sverremark-Ekstrom E; Jenmalm M C
    Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology (2009), 39 (12), 1842-51 ISSN:.
    INTRODUCTION: Among sensitized infants, those with high, as compared with low levels, of salivary secretory IgA (SIgA) are less likely to develop allergic symptoms. Also, early colonization with certain gut microbiota, e.g. Lactobacilli and Bifidobacterium species, might be associated with less allergy development. Although animal and in vitro studies emphasize the role of the commensal gut microbiota in the development of the immune system, the influence of the gut microbiota on immune development in infants is unclear. OBJECTIVE: To assess whether early colonization with certain gut microbiota species associates with mucosal and systemic immune responses i.e. salivary SIgA and the spontaneous Toll-like receptor (TLR) 2 and TLR4 mRNA expression and lipopolysaccharide (LPS)-induced cytokine/chemokine responses in peripheral blood mononuclear cells (PBMCs). METHODS: Fecal samples were collected at 1 week, 1 month and 2 months after birth from 64 Swedish infants, followed prospectively up to 5 years of age. Bacterial DNA was analysed with real-time PCR using primers binding to Clostridium difficile, four species of bifidobacteria, two lactobacilli groups and Bacteroides fragilis. Saliva was collected at age 6 and 12 months and at 2 and 5 years and SIgA was measured with ELISA. The PBMCs, collected 12 months after birth, were analysed for TLR2 and TLR4 mRNA expression with real-time PCR. Further, the PBMCs were stimulated with LPS, and cytokine/chemokine responses were measured with Luminex. RESULTS: The number of Bifidobacterium species in the early fecal samples correlated significantly with the total levels of salivary SIgA at 6 months. Early colonization with Bifidobacterium species, lactobacilli groups or C. difficile did not influence TLR2 and TLR4 expression in PBMCs. However, PBMCs from infants colonized early with high amounts of Bacteroides fragilis expressed lower levels of TLR4 mRNA spontaneously. Furthermore, LPS-induced production of inflammatory cytokines and chemokines, e.g. IL-6 and CCL4 (MIP-1 beta), was inversely correlated to the relative amounts of Bacteroides fragilis in the early fecal samples. CONCLUSION: Bifidobacterial diversity may enhance the maturation of the mucosal SIgA system and early intense colonization with Bacteroides fragilis might down-regulate LPS responsiveness in infancy.
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    Sonnenburg, E. D.; Sonnenburg, J. L. Starving our Microbial Self: The Deleterious Consequences of a Diet Deficient in Microbiota-Accessible Carbohydrates. Cell Metabolism 2014, 20 (5), 779– 786,  DOI: 10.1016/j.cmet.2014.07.003
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    Starving our Microbial Self: The Deleterious Consequences of a Diet Deficient in Microbiota-Accessible Carbohydrates
    Sonnenburg, Erica D.; Sonnenburg, Justin L.
    Cell Metabolism (2014), 20 (5), 779-786CODEN: CMEEB5; ISSN:1550-4131. (Elsevier Inc.)
    A review. The gut microbiota of a healthy person may not be equiv. to a healthy microbiota. It is possible that the Western microbiota is actually dysbiotic and predisposes individuals to a variety of diseases. The asym. plasticity between the relatively stable human genome and the more malleable gut microbiome suggests that incompatibilities between the two could rapidly arise. The Western lifestyle, which includes a diet low in microbiota-accessible carbohydrates (MACs), has selected for a microbiota with altered membership and functionality compared to those of groups living traditional lifestyles. Interactions between resident microbes and host leading to immune dysregulation may explain several diseases that share inflammation as a common basis. The low-MAC Western diet results in poor prodn. of gut microbiota-generated short-chain fatty acids (SCFAs), which attenuate inflammation through a variety of mechanisms in mouse models. Studies focused on modern and traditional societies, combined with animal models, are needed to characterize the connection between diet, microbiota compn., and function. Differentiating between an optimal microbiota, one that increases disease risk, and one that is causative or potentiates disease will be required to further understand both the etiol. and possible treatments for health problems related to microbiota dysbiosis.
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    Arvik, T. Grape (Vitis vinifera) Seed and Skin Flours Contribute Flavor and Functionality to Baked Goods. Cereal Food World 2012, 57 (6), 262– 264,  DOI: 10.1094/CFW-57-6-0262
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    Soliman, G. A. Dietary Fiber, Atherosclerosis, and Cardiovascular Disease. Nutrients 2019, 11 (5), 1155,  DOI: 10.3390/nu11051155
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    Dietary fiber, atherosclerosis, and cardiovascular disease
    Soliman, Ghada A.
    Nutrients (2019), 11 (5), 1155CODEN: NUTRHU; ISSN:2072-6643. (MDPI AG)
    A review. Observational studies have shown that dietary fiber intake is assocd. with decreased risk of cardiovascular disease. Dietary fiber is a non-digestible form of carbohydrates, due to the lack of the digestive enzyme in humans required to digest fiber. Dietary fibers and lignin are intrinsic to plants and are classified according to their water soly. properties as either sol. or insol. fibers. Water-sol. fibers include pectin, gums, mucilage, fructans, and some resistant starches. They are present in some fruits, vegetables, oats, and barley. Sol. fibers have been shown to lower blood cholesterol by several mechanisms. On the other hand, water-insol. fibers mainly include lignin, cellulose, and hemicellulose; whole-grain foods, bran, nuts, and seeds are rich in these fibers. Water-insol. fibers have rapid gastric emptying, and as such may decrease the intestinal transit time and increase fecal bulk, thus promoting digestive regularity. In addn. to dietary fiber, isolated and extd. fibers are known as functional fiber and have been shown to induce beneficial health effects when added to food during processing. The recommended daily allowances (RDAs) for total fiber intake for men and women aged 19-50 are 38 g/day and 25 g/day, resp. It is worth noting that the RDA recommendations are for healthy people and do not apply to individuals with some chronic diseases. Studies have shown that most Americans do not consume the recommended intake of fiber. This review will summarize the current knowledge regarding dietary fiber, sources of food contg. fiber, atherosclerosis, and heart disease risk redn.
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    Colodel, C.; Vriesmann, L. C.; Teofilo, R. F.; de Oliveira Petkowicz, C. L. Optimization of acid-extraction of pectic fraction from grape (Vitis vinifera cv. Chardonnay) pomace, a Winery Waste. Int. J. Biol. Macromol. 2020, 161, 204– 213,  DOI: 10.1016/j.ijbiomac.2020.05.272
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    Optimization of acid-extraction of pectic fraction from grape (Vitis vinifera cv. Chardonnay) pomace, a Winery Waste
    Colodel, Cristiane; Vriesmann, Lucia Cristina; Teofilo, Reinaldo Francisco; de Oliveira Petkowicz, Carmen Lucia
    International Journal of Biological Macromolecules (2020), 161 (), 204-213CODEN: IJBMDR; ISSN:0141-8130. (Elsevier B.V.)
    Chardonnay grape pomace was evaluated as a source of pectin. A central composite design was used in order to det. the effect of pH, extn. time (Et) and liq.: solid ratio (LS) on the yield and uronic acid (UA) content of the pectins extd. using boiling HNO3 soln. The optimized extn. condition to reach the max. yield and UA was pH = 2.08, Et = 135.23 min and LS = 35.11 mL/g, resulting in theor. yield of 12.8% and UA of 64.4%. The exptl. yield of the pectic fraction obtained under the optimized conditions (GPOP) was 11.1% and the UA was 56.8%. GPOP had ∼25% glucose. It was treated with α-amylase and amyloglucosidase, resulting in the fraction α-GPOP. The starch-free pectic fraction was composed of 63.5% UA, 7.8% rhamnose, 6.0% arabinose, 13.6% galactose and minor amts. of other neutral monosaccharides. It contained a low-methoxyl pectin (degree of methyl-esterification 18.1%) and had an av. molar mass of 154,100 g/mol. It consisted of 55.7% homogalacturonan and 35.2% rhamnogalacturonan I (RG-I). NMR analyses suggest that RG-I portion of α-GPOP is highly branched by short chains or single residues of arabinose and galactose.
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    Barrett, A. H.; Farhadi, N. F.; Smith, T. J. Slowing starch digestion and inhibiting digestive enzyme activity using plant flavanols/tannins - A review of efficacy and mechanisms. Lwt-Food Sci. Technol. 2018, 87, 394– 399,  DOI: 10.1016/j.lwt.2017.09.002
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    Slowing starch digestion and inhibiting digestive enzyme activity using plant flavanols/tannins- A review of efficacy and mechanisms
    Barrett, Ann H.; Farhadi, Nicole F.; Smith, Tracey J.
    LWT--Food Science and Technology (2018), 87 (), 394-399CODEN: LSTWB3; ISSN:0023-6438. (Elsevier Ltd.)
    A review. Polyphenols are a heterogeneous group of phytochems. that are found in plant-based foods, which have antioxidant and anti-inflammatory properties that may ultimately help protect against chronic diseases, such as cancer and cardiometabolic disease. Flavanols (i.e., a subclass of polyphenols), in particular, have been shown to promote glycemic control when consumed with a high-carbohydrate contg. food item. Flavanol structures include complex, hydroxylated arrangements, also known as "tannins", which assoc. strongly with proteins and thus are notable for their effect on dietary enzymes. Tannins are furthermore divided into non-hydrolysable proanthocyanidin (PAC) and hydrolysable fractions. This review includes recent findings of in vivo and in vitro effects of flavanols/tannins on blood glucose management and inhibition of the digestive enzymes α-amylase and α-glucosidase. Mechanisms underlying the interaction between flavanol structure and glycemic response (e.g., inhibition of starch digestion, altered transport and absorption of glucose, and the altered secretion of gastrointestinal hormones) are discussed, with an emphasis on the mol. basis for flavanol-enzyme interactions that lead to inhibition of enzyme activity.
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    Chakraborty, S.; Mandal, J.; Yang, T.; Cheng, X.; Yeo, J. Y.; McCarthy, C. G.; Wenceslau, C. F.; Koch, L. G.; Hill, J. W.; Vijay-Kumar, M.; Joe, B. Metabolites and Hypertension: Insights into Hypertension as a Metabolic Disorder: 2019 Harriet Dustan Award. Hypertension 2020, 75 (6), 1386– 1396,  DOI: 10.1161/HYPERTENSIONAHA.120.13896
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    Metabolites and Hypertension: Insights into Hypertension as a Metabolic Disorder: 2019 Harriet Dustan Award
    Chakraborty, Saroj; Mandal, Juthika; Yang, Tao; Cheng, Xi; Yeo, Ji-Youn; McCarthy, Cameron G.; Wenceslau, Camilla F.; Koch, Lauren G.; Hill, Jennifer W.; Vijay-Kumar, Matam; Joe, Bina
    Hypertension (2020), 75 (6), 1386-1396CODEN: HPRTDN; ISSN:0194-911X. (Lippincott Williams & Wilkins)
    For over 100 years, essential hypertension has been researched from different perspectives ranging from genetics, physiol., and immunol. to more recent ones encompassing microbiol. (microbiota) as a previously underappreciated field of study contributing to the cause of hypertension. Each field of study in isolation has uniquely contributed to a variety of underlying mechanisms of blood pressure regulation. Even so, clin. management of essential hypertension has remained somewhat static. We, therefore, asked if there are any converging lines of evidence from these individual fields that could be amenable for a better clin. prognosis. Accordingly, here we present converging evidence which support the view that metabolic dysfunction underlies essential hypertension.
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    Gibson, G. R.; Hutkins, R.; Sanders, M. E.; Prescott, S. L.; Reimer, R. A.; Salminen, S. J.; Scott, K.; Stanton, C.; Swanson, K. S.; Cani, P. D.; Verbeke, K.; Reid, G. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat. Rev. Gastroenterol Hepatol 2017, 14 (8), 491– 502,  DOI: 10.1038/nrgastro.2017.75
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    Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics
    Gibson Glenn R; Hutkins Robert; Sanders Mary Ellen; Prescott Susan L; Reimer Raylene A; Salminen Seppo J; Scott Karen; Stanton Catherine; Swanson Kelly S; Cani Patrice D; Verbeke Kristin; Reid Gregor
    Nature reviews. Gastroenterology & hepatology (2017), 14 (8), 491-502 ISSN:.
    In December 2016, a panel of experts in microbiology, nutrition and clinical research was convened by the International Scientific Association for Probiotics and Prebiotics to review the definition and scope of prebiotics. Consistent with the original embodiment of prebiotics, but aware of the latest scientific and clinical developments, the panel updated the definition of a prebiotic: a substrate that is selectively utilized by host microorganisms conferring a health benefit. This definition expands the concept of prebiotics to possibly include non-carbohydrate substances, applications to body sites other than the gastrointestinal tract, and diverse categories other than food. The requirement for selective microbiota-mediated mechanisms was retained. Beneficial health effects must be documented for a substance to be considered a prebiotic. The consensus definition applies also to prebiotics for use by animals, in which microbiota-focused strategies to maintain health and prevent disease is as relevant as for humans. Ultimately, the goal of this Consensus Statement is to engender appropriate use of the term 'prebiotic' by relevant stakeholders so that consistency and clarity can be achieved in research reports, product marketing and regulatory oversight of the category. To this end, we have reviewed several aspects of prebiotic science including its development, health benefits and legislation.
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    Newburg, D. S. Neonatal protection by an innate immune system of human milk consisting of oligosaccharides and glycans1. Journal of Animal Science 2009, 87, 26– 34,  DOI: 10.2527/jas.2008-1347
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    Neonatal protection by an innate immune system of human milk consisting of oligosaccharides and glycans
    Newburg D S
    Journal of animal science (2009), 87 (13 Suppl), 26-34 ISSN:.
    This review discusses the role of human milk glycans in protecting infants, but the conclusion that the human milk glycans constitute an innate immune system whereby the mother protects her offspring may have general applicability in all mammals, including species of commercial importance. Infants that are not breastfed have a greater incidence of severe diarrhea and respiratory diseases than those who are breastfed. In the past, this had been attributed primarily to human milk secretory antibodies. However, the oligosaccharides are major components of human milk, and milk is also rich in other glycans, including glycoproteins, mucins, glycosaminoglycans, and glycolipids. These milk glycans, especially the oligosaccharides, are composed of thousands of components. The milk factor that promotes gut colonization by Bifidobacterium bifidum was found to be a glycan, and such prebiotic characteristics may contribute to protection against infectious agents. However, the ability of human milk glycans to protect the neonate seems primarily to be due to their inhibition of pathogen binding to their host cell target ligands. Many such examples include specific fucosylated oligosaccharides and glycans that inhibit specific pathogens. Most human milk oligosaccharides are fucosylated, and their production depends on fucosyltransferase enzymes; mutations in these fucosyltransferase genes are common and underlie the various Lewis blood types in humans. Variable expression of specific fucosylated oligosaccharides in milk, also a function of these genes (and maternal Lewis blood type), is significantly associated with the risk of infectious disease in breastfed infants. Human milk also contains major quantities and large numbers of sialylated oligosaccharides, many of which are also present in bovine colostrum. These could similarly inhibit several common viral pathogens. Moreover, human milk oligosaccharides strongly attenuate inflammatory processes in the intestinal mucosa. These results support the hypothesis that oligosaccharides and other glycans are the major constituents of an innate immune system of human milk whereby the mother protects her infant from enteric and other pathogens through breastfeeding. These protective glycans may prove useful as a basis for the development of novel prophylactic and therapeutic agents that inhibit disease by mucosal pathogens in many species.
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    Garrido, D.; Ruiz-Moyano, S.; Mills, D. A. Release and utilization of N-acetyl-D-glucosamine from human milk oligosaccharides by Bifidobacterium longum subsp. infantis. Anaerobe 2012, 18 (4), 430– 435,  DOI: 10.1016/j.anaerobe.2012.04.012
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    Release and utilization of N-acetyl-d-glucosamine from human milk oligosaccharides by Bifidobacterium longum subsp. infantis
    Garrido, Daniel; Ruiz-Moyano, Santiago; Mills, David A.
    Anaerobe (2012), 18 (4), 430-435CODEN: ANAEF8; ISSN:1075-9964. (Elsevier Ltd.)
    Human milk contains high amts. of complex oligosaccharides, which can be utilized esp. by Bifidobacterium species in the infant gut as a carbon and energy source. N-acetyl-d-glucosamine is a building block of these oligosaccharides, and mol. details on the release and utilization of this monosaccharide are not fully understood. In this work we have studied some of the enzymic properties of three N-acetyl-β-D-hexosaminidases encoded by the genome of the intestinal isolate Bifidobacterium longum subsp. infantis ATCC 15697 and the gene expression of the corresponding genes during bacterial growth on human milk oligosaccharides. These enzymes belong to the glycosyl hydrolase family 20, with several homologs in bifidobacteria. Their optimum pH was 5.0 and optimum temp. was 37 °C. The three enzymes were active on the GlcNAcβ1-3 linkage found in lacto-N-tetraose, the most abundant human milk oligosaccharide. Blon_0459 and Blon_0732, but not Blon_2355, cleaved branched GlcNAcβ1-6 linkages found in lacto-N-hexaose, another oligosaccharide abundant in breast milk. Bifidobacterium infantis N-acetyl-β-D-hexosaminidases were induced during early growth in vitro on human milk oligosaccharides, and also during growth on lacto-N-tetraose or lacto-N-neotetraose. The up-regulation of enzymes that convert this monosaccharide into UDP-N-acetylglucosamine by human milk oligosaccharides suggested that this activated sugar is used in peptidoglycan biosynthesis. These results emphasize the complexity of human milk oligosaccharide consumption by this infant intestinal isolate, and provide new clues into this process.
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    Karav, S.; Le Parc, A.; Leite Nobrega de Moura Bell, J. M.; Frese, S. A.; Kirmiz, N.; Block, D. E.; Barile, D.; Mills, D. A. Oligosaccharides Released from Milk Glycoproteins Are Selective Growth Substrates for Infant-Associated Bifidobacteria. Appl. Environ. Microbiol. 2016, 82 (12), 3622– 3630,  DOI: 10.1128/AEM.00547-16
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    Oligosaccharides released from milk glycoproteins are selective growth substrates for infant-associated Bifidobacteria
    Karav, Sercan; Le Parc, Annabelle; Bell, Juliana Maria Leite Nobrega de Moura; Frese, Steven A.; Kirmiz, Nina; Block, David E.; Barile, Daniela; Mills, David A.
    Applied and Environmental Microbiology (2016), 82 (12), 3622-3630CODEN: AEMIDF; ISSN:1098-5336. (American Society for Microbiology)
    Milk, in addn. to nourishing the neonate, provides a range of complex glycans whose construction ensures a specific enrichment of key members of the gut microbiota in the nursing infant, a consortium known as the milk-oriented microbiome. Milk glycoproteins are thought to function similarly, as specific growth substrates for bifidobacteria common to the breast-fed infant gut. Recently, a cell wall-assocd. endo-β-N-acetylglucosaminidase (EndoBI-1) found in various infant-borne bifidobacteria was shown to remove a range of intact N-linked glycans. We hypothesized that these released oligosaccharide structures can serve as a sole source for the selective growth of bifidobacteria. We demonstrated that EndoBI-1 released N-glycans from concd. bovine colostrum at the pilot scale. EndoBI-1-released N-glycans supported the rapid growth of Bifidobacterium longum subsp. infantis, a species that grows well on human milk oligosaccharides, but did not support growth of Bifidobacterium animalis subsp. lactis, a species which does not. Conversely, B. infantis ATCC 15697 did not grow on the deglycosylated milk protein fraction, clearly demonstrating that the glycan portion of milk glycoproteins provided the key substrate for growth. Mass spectrometry-based profiling revealed that B. infantis consumed 73% of neutral and 92% of sialylated N-glycans, while B. lactis degraded only 11% of neutral and virtually no (<1%) sialylated N-glycans. These results provide mechanistic support that N-linked glycoproteins from milk serve as selective substrates for the enrichment of infant-assocd. bifidobacteria capable of carrying out the initial deglycosylation. Moreover, released N-glycans were better growth substrates than the intact milk glycoproteins, suggesting that EndoBI-1 cleavage is a key initial step in consumption of glycoproteins. Finally, the variety of N-glycans released from bovine milk glycoproteins suggests that they may serve as novel prebiotic substrates with selective properties similar to those of human milk oligosaccharides.
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    Apolinar-Valiente, R.; Williams, P.; Doco, T. Recent advances in the knowledge of wine oligosaccharides. Food Chem. 2021, 342, 128330,  DOI: 10.1016/j.foodchem.2020.128330
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    Recent advances in the knowledge of wine oligosaccharides
    Apolinar-Valiente, Rafael; Williams, Pascale; Doco, Thierry
    Food Chemistry (2021), 342 (), 128330CODEN: FOCHDJ; ISSN:0308-8146. (Elsevier Ltd.)
    A review. Oligosaccharides are carbohydrates with a low polymn. degree contg. between three and fifteen monosaccharide residues covalently linked through glycosidic bonds. Oligosaccharides are related to plant defense responses and possess beneficial attributes for human health. Research has focused in wine oligosaccharides only in the last decade. In this paper, a summary of these works is provided. They include: (i) wine oligosaccharides origins, (ii) techniques for isolating oligosaccharide fraction and detg. their content, compn. and structure, (iii) their dependence on the grape origin and cultivar and winemaking process, and (iv) the connection between oligosaccharides and wine sensorial attributes. Further research is required regarding the impact of agricultural aspects and winemaking techniques on wine oligosaccharides. The knowledge concerning their influence on sensorial and physicochem. properties of wines and on human health should also be improved. The implementation of lab. methods will provide better understanding of these compds. and their performance within wine's matrix.
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    Yan, Y. L.; Hu, Y.; Ganzle, M. G. Prebiotics, FODMAPs and dietary fiber - conflicting concepts in development of functional food products?. Curr. Opin Food Sci. 2018, 20, 30– 37,  DOI: 10.1016/j.cofs.2018.02.009
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    Quiros-Sauceda, A. E.; Palafox-Carlos, H.; Sayago-Ayerdi, S. G.; Ayala-Zavala, J. F.; Bello-Perez, L. A.; Alvarez-Parrilla, E.; de la Rosa, L. A.; Gonzalez-Cordova, A. F.; Gonzalez-Aguilar, G. A. Dietary fiber and phenolic compounds as functional ingredients: interaction and possible effect after ingestion. Food Funct 2014, 5 (6), 1063– 72,  DOI: 10.1039/C4FO00073K
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    Dietary fiber and phenolic compounds as functional ingredients: interaction and possible effect after ingestion
    Quiros-Sauceda, A. E.; Palafox-Carlos, H.; Sayago-Ayerdi, S. G.; Ayala-Zavala, J. F.; Bello-Perez, L. A.; Alvarez-Parrilla, E.; de la Rosa, L. A.; Gonzalez-Cordova, A. F.; Gonzalez-Aguilar, G. A.
    Food & Function (2014), 5 (6), 1063-1072CODEN: FFOUAI; ISSN:2042-6496. (Royal Society of Chemistry)
    A review. Dietary fiber and phenolic compds. are two recognized dietary factors responsible for potential effects on human health; therefore, they have been widely used to increase functionality of some foods. This paper focuses on showing the use of both substances as functional ingredients for enriching foods, and at the same time, describes the use of a single material that combines the properties of the two types of substances. The last part of the work describes some facts related to the interaction between dietary fiber and phenolic compds., which could affect the bioaccessibility and absorption of phenolics in the gut. In this sense, the purpose of the present review is to compile and analyze evidence relating to the use of dietary fiber and phenolic compds. to enhance technol. and nutritional properties of foods and hypothesize some of the possible effects in the gut after their ingestion.
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    Walle, T.; Otake, Y.; Walle, U. K.; Wilson, F. A. Quercetin Glucosides Are Completely Hydrolyzed in Ileostomy Patients before Absorption. Journal of Nutrition 2000, 130 (11), 2658– 2661,  DOI: 10.1093/jn/130.11.2658
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    Quercetin glucosides are completely hydrolyzed in ileostomy patients before absorption
    Walle, Thomas; Otake, Yoko; Walle, U. Kristina; Wilson, Frederick A.
    Journal of Nutrition (2000), 130 (11), 2658-2661CODEN: JONUAI; ISSN:0022-3166. (American Society for Nutritional Sciences)
    Flavonoids, dietary components of vegetables, fruits and beverages, may protect against coronary heart disease, stroke, and cancer. The bioavailability of these compds. is questionable. A previous study of the most abundant flavonoid, quercetin, in ileostomy patients suggested a 52% absorption of its major dietary forms, monoglucoside (QMG) and diglucoside (QDG), from an onion meal, but this study was based on indirect measurements after acid hydrolysis. Because human intestinal Caco-2 cell monolayers show minimal absorption of the glucosides, we repeated the study in ileostomy patients, using molecularly specific anal. methodol. for the intact glucosides and quercetin. The onion meal had high concns. of both QMG and QDG with only trace amts. of free quercetin aglycon. The intake of QMG and QDG in 4 patients ranged 10.9-51.6 mg. No QMG or QDG was detected in the ileostomy fluid. The amts. of the free quercetin in the fluid were substantial, 2.9-11.3 mg. This corresponded to 19.5-35.2% of total quercetin glucosides ingested, implying absorption of 64.5-80.7%. Thus, both QMG and QDG are efficiently hydrolyzed in the small intestine by β-glucosidases to quercetin, most of which is then absorbed.
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    Proenca, C.; Rufino, A. T.; Ferreira de Oliveira, J. M. P.; Freitas, M.; Fernandes, P. A.; Silva, A. M. S.; Fernandes, E. Inhibitory activity of flavonoids against human sucrase-isomaltase (alpha-glucosidase) activity in a Caco-2/TC7 cellular model. Food Funct 2022, 13 (3), 1108– 1118,  DOI: 10.1039/D1FO02995A
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    Inhibitory activity of flavonoids against human sucrase-isomaltase (α-glucosidase) activity in a Caco-2/TC7 cellular model
    Proenca, Carina; Rufino, Ana T.; Ferreira de Oliveira, Jose Miguel P.; Freitas, Marisa; Fernandes, Pedro A.; Silva, Artur M. S.; Fernandes, Eduarda
    Food & Function (2022), 13 (3), 1108-1118CODEN: FFOUAI; ISSN:2042-6496. (Royal Society of Chemistry)
    Type 2 diabetes (T2D) is the most common form of diabetes, and the no. of people with this metabolic disease is steadily increasing worldwide. Among the available antidiabetic agents, α-glucosidase inhibitors are the most effective at reducing postprandial hyperglycemia (PPHG), one of the main characteristics of T2D. However, most of the studies that have been performed have used the more readily available rat intestinal prepns. or yeast α-glucosidase as the enzyme source, which despite being useful and cost effective, have a questionable physiol. value. The present study evaluates the inhibitory activity of a selected group of flavonoids against human sucrase-isomaltase (SI), the α-glucosidase found in Caco-2/TC7 cells. A microassay using the physiol. substrates sucrose and maltose, and a synthetic substrate, p-nitrophenyl-α-D-glucopyranoside (pNPG) was performed. The most active flavonoid was compd. 4 (melanoxetin), presenting an IC50 value similar using the two natural substrates. In contrast, the tested flavonoids were not effective at inhibiting SI, when pNPG was used as a substrate. Hydroxylation of flavonoids at C-3 of the C ring, at C-3' and C-4' of the B ring, and at C-7 and C-8 of the A ring were the features that improved the inhibitory activity of flavonoids against human SI. These phenolic compds. deserve further exploration as alternatives to the currently available α-glucosidase inhibitors. The present study also demonstrates that the non-clin. in vitro studies conducted for the evaluation of α-glucosidase activity should use the human source rather than surrogate sources of α-glucosidase.
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    Ottaviani, J. I.; Britten, A.; Lucarelli, D.; Luben, R.; Mulligan, A. A.; Lentjes, M. A.; Fong, R.; Gray, N.; Grace, P. B.; Mawson, D. H.; Tym, A.; Wierzbicki, A.; Forouhi, N. G.; Khaw, K. T.; Schroeter, H.; Kuhnle, G. G. C. Biomarker-estimated flavan-3-ol intake is associated with lower blood pressure in cross-sectional analysis in EPIC Norfolk. Sci. Rep 2020, 10 (1), 17964,  DOI: 10.1038/s41598-020-74863-7
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    Biomarker-estimated flavan-3-ol intake is associated with lower blood pressure in cross-sectional analysis in EPIC Norfolk
    Ottaviani, Javier I.; Britten, Abigail; Lucarelli, Debora; Luben, Robert; Mulligan, Angela A.; Lentjes, Marleen A.; Fong, Reedmond; Gray, Nicola; Grace, Philip B.; Mawson, Deborah H.; Tym, Amy; Wierzbicki, Antonia; Forouhi, Nita G.; Khaw, Kay-Tee; Schroeter, Hagen; Kuhnle, Gunter G. C.
    Scientific Reports (2020), 10 (1), 17964CODEN: SRCEC3; ISSN:2045-2322. (Nature Research)
    Flavan-3-ols are a group of bioactive compds. that have been shown to improve vascular function in intervention studies. They are therefore of great interest for the development of dietary recommendation for the prevention of cardio-vascular diseases. However, there are currently no reliable data from observational studies, as the high variability in the flavan-3-ol content of food makes it difficult to est. actual intake without nutritional biomarkers. In this study, we investigated cross-sectional assocns. between biomarker-estd. flavan-3-ol intake and blood pressure and other CVD risk markers, as well as longitudinal assocns. with CVD risk in 25,618 participants of the European Prospective Investigation into Cancer (EPIC) Norfolk cohort. High flavan-3-ol intake, achievable as part of an habitual diet, was assocd. with a significantly lower systolic blood pressure (- 1.9 (- 2.7; - 1.1) mmHg in men and - 2.5 (- 3.3; - 1.8) mmHg in women; lowest vs highest decile of biomarker), comparable to adherence to a Mediterranean Diet or moderate salt redn. Subgroup analyses showed that hypertensive participants had stronger inverse assocn. between flavan-3-ol biomarker and systolic blood pressure when compared to normotensive participants. Flavanol intake could therefore have a role in the maintenance of cardiovascular health on a population scale.
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    Ottaviani, J. I.; Heiss, C.; Spencer, J. P. E.; Kelm, M.; Schroeter, H. Recommending flavanols and procyanidins for cardiovascular health: Revisited. Mol. Aspects Med. 2018, 61, 63– 75,  DOI: 10.1016/j.mam.2018.02.001
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    Recommending flavanols and procyanidins for cardiovascular health: Revisited
    Ottaviani, Javier I.; Heiss, Christian; Spencer, Jeremy P. E.; Kelm, Malte; Schroeter, Hagen
    Molecular Aspects of Medicine (2018), 61 (), 63-75CODEN: MAMED5; ISSN:0098-2997. (Elsevier Ltd.)
    The last 8 years have seen significant developments in our understanding of dietary flavanols and procyanidins in the context of human health and nutrition. During the same time, recognition of the importance of nutrition in primary disease prevention and health maintenance has increased. In addn., the concept of dietary bioactives (food constituents that although not essential to human life and procreation, may nevertheless play an important role in disease risk redn., primary disease prevention, and healthy aging) has been created and developed. Applying assessment criteria specific to health maintenance and primary disease prevention, we aimed at broadly evaluating and discussing currently available data on flavanols and procyanidins, with an eye towards potentially advancing the future development of dietary guidelines and public health recommendations. Novel insights and advancements as well as current gaps and shortcomings in our understanding are identified and discussed. While centered on flavanols and procyanidins, the outcomes of this review may also have broader relevance for the further development of the concept of bioactives, and any future framework for the assessment of their role in human health and nutrition.
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    Influence of vitamin P (vitamin C2) upon the amount of ascorbic acid in the organs of the guinea pig
    COTEREAU H; GABE M
    Nature (1948), 161 (4093), 557 ISSN:0028-0836.
    There is no expanded citation for this reference.
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    Hertog, M. G.; Feskens, E. J.; Hollman, P. C.; Katan, M. B.; Kromhout, D. Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study. Lancet 1993, 342 (8878), 1007– 11,  DOI: 10.1016/0140-6736(93)92876-U
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    Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study
    Hertog M G; Feskens E J; Hollman P C; Katan M B; Kromhout D
    Lancet (London, England) (1993), 342 (8878), 1007-11 ISSN:0140-6736.
    Flavonoids are polyphenolic antioxidants naturally present in vegetables, fruits, and beverages such as tea and wine. In vitro, flavonoids inhibit oxidation of low-density lipoprotein and reduce thrombotic tendency, but their effects on atherosclerotic complications in human beings are unknown. We measured the content in various foods of the flavonoids quercetin, kaempferol, myricetin, apigenin, and luteolin. We then assessed the flavonoid intake of 805 men aged 65-84 years in 1985 by a cross-check dietary history; the men were then followed up for 5 years. Mean baseline flavonoid intake was 25.9 mg daily. The major sources of intake were tea (61%), onions (13%), and apples (10%). Between 1985 and 1990, 43 men died of coronary heart disease. Fatal or non-fatal myocardial infarction occurred in 38 of 693 men with no history of myocardial infarction at baseline. Flavonoid intake (analysed in tertiles) was significantly inversely associated with mortality from coronary heart disease (p for trend = 0.015) and showed an inverse relation with incidence of myocardial infarction, which was of borderline significance (p for trend = 0.08). The relative risk of coronary heart disease mortality in the highest versus the lowest tertile of flavonoid intake was 0.42 (95% CI 0.20-0.88). After adjustment for age, body-mass index, smoking, serum total and high-density-lipoprotein cholesterol, blood pressure, physical activity, coffee consumption, and intake of energy, vitamin C, vitamin E, beta-carotene, and dietary fibre, the risk was still significant (0.32 [0.15-0.71]). Intakes of tea, onions, and apples were also inversely related to coronary heart disease mortality, but these associations were weaker. Flavonoids in regularly consumed foods may reduce the risk of death from coronary heart disease in elderly men.
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    Hertog, M. G.; Kromhout, D.; Aravanis, C.; Blackburn, H.; Buzina, R.; Fidanza, F.; Giampaoli, S.; Jansen, A.; Menotti, A.; Nedeljkovic, S. Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study. Arch Intern Med. 1995, 155 (4), 381– 6,  DOI: 10.1001/archinte.1995.00430040053006
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    Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study
    Hertog, Michael G. L.; Kromhout, Daan; Aravanis, Christ; Blackburn, Henry; Buzina, Ratko; Fidanza, Flaminio; Giampaoli, Simona; Jansen, Annemarie; Menotti, Alessandro; et al.
    Archives of Internal Medicine (1995), 155 (4), 381-6CODEN: AIMDAP; ISSN:0003-9926.
    This study made an attempt to det. whether flavonoid intake explains differences in mortality rates from chronic diseases (coronary heart disease, cancer, other causes) between populations in a 25 yr study. Av. intake of antioxidant flavonoids was inversely assocd. with mortality from coronary heart disease and explained about 25% of the variance in coronary heart disease rates in the 16 cohorts (7 countries studied). In multivariate anal., intake of satd. fat (73%; P=.0001), flavonoid intake (8%; P=.01), and percentage of smokers per cohort (9%; P=.03) explained together, independent of intake of alc. and antioxidant vitamins, 90% of the variance in coronary heart disease rates. Flavonoid intake was not independently assocd. with mortality from other causes. Av. flavonoid intake may partly contribute to differences in coronary heart disease mortality across populations, but it does not seem to be an important determinant of cancer mortality.
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    Tresserra-Rimbau, A.; Rimm, E. B.; Medina-Remón, A.; Martínez-González, M. A.; de la Torre, R.; Corella, D.; Salas-Salvadó, J.; Gómez-Gracia, E.; Lapetra, J.; Arós, F.; Fiol, M.; Ros, E.; Serra-Majem, L.; Pintó, X.; Saez, G. T.; Basora, J.; Sorlí, J. V.; Martínez, J. A.; Vinyoles, E.; Ruiz-Gutiérrez, V.; Estruch, R.; Lamuela-Raventós, R. M. Inverse association between habitual polyphenol intake and incidence of cardiovascular events in the PREDIMED study. Nutrition, Metabolism and Cardiovascular Diseases 2014, 24 (6), 639– 647,  DOI: 10.1016/j.numecd.2013.12.014
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    Inverse association between habitual polyphenol intake and incidence of cardiovascular events in the PREDIMED study
    Tresserra-Rimbau, A.; Rimm, E. B.; Medina-Remon, A.; Martinez-Gonzalez, M. A.; de la Torre, R.; Corella, D.; Salas-Salvado, J.; Gomez-Gracia, E.; Lapetra, J.; Aros, F.; Fiol, M.; Ros, E.; Serra-Majem, L.; Pinto, X.; Saez, G. T.; Basora, J.; Sorli, J. V.; Martinez, J. A.; Vinyoles, E.; Ruiz-Gutierrez, V.; Estruch, R.; Lamuela-Raventos, R. M.
    Nutrition, Metabolism & Cardiovascular Diseases (2014), 24 (6), 639-647CODEN: NMCDEE; ISSN:0939-4753. (Elsevier B.V.)
    Epidemiol. and biol. evidence supports an inverse assocn. between polyphenol consumption and the risk of cardiovascular disease (CVD). However, no previous studies have prospectively evaluated the relationship between polyphenol intake and the incidence of CVD in such a comprehensive way. The aim was to evaluate the assocn. between intakes of total polyphenol and polyphenol subgroups, and the risk of major cardiovascular events (myocardial infarction, stroke or death from cardiovascular causes) in the PREDIMED study.The present work is an observational study within the PREDIMED trial. Over an av. of 4.3 years of follow-up, there were 273 confirmed cases of CVD among the 7172 participants (96.3%) who completed a validated 137-item food frequency questionnaire (FFQ) at baseline. Polyphenol consumption was calcd. by matching food consumption data from the FFQ with the Phenol-Explorer database on polyphenol content of each reported food. After multivariate adjustment, a 46% redn. in risk of CVD risk was obsd. comparing Q5 vs. Q1 of total polyphenol intake (HR = 0.54; 95% confidence interval [CI] = 0.33-0.91; P-trend = 0.04). The polyphenols with the strongest inverse assocns. were flavanols (HR = 0.40; CI 0.23-0.72; P-trend = 0.003), lignans (HR = 0.51; CI 0.30-0.86; P-trend = 0.007), and hydroxybenzoic acids (HR = 0.47; CI 0.26-0.86; P-trend 0.02).Greater intake of polyphenols, esp. from lignans, flavanols, and hydroxybenzoic acids, was assocd. with decreased CVD risk. Clin. trials are needed to confirm this effect and establish accurate dietary recommendations. Clin. trial registry: International Std. Randomized Controlled Trial No. (ISRCTN of London, England) 35739639.
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  74. 74
    Tresserra-Rimbau, A.; Castro-Barquero, S.; Vitelli-Storelli, F.; Becerra-Tomas, N.; Vázquez-Ruiz, Z.; Díaz-López, A.; Corella, D.; Castañer, O.; Romaguera, D.; Vioque, J.; Alonso-Gómez, Á. M.; Wärnberg, J.; Martínez, J. A.; Serra-Majem, L.; Estruch, R.; Tinahones, F. J.; Lapetra, J.; Pintó, X.; Tur, J. A.; López-Miranda, J.; García-Molina, L.; Delgado-Rodríguez, M.; Matía-Martín, P.; Daimiel, L.; Rubín-García, M.; Vidal, J.; Galdon, A.; Ros, E.; Basterra-Gortari, F. J.; Babio, N.; Sorlí, J. V.; Hernáez, Á.; Konieczna, J.; Notario-Barandiaran, L.; Tojal-Sierra, L.; Pérez-López, J.; Abete, I.; Álvarez-Pérez, J.; Fernández-García, J. C.; Santos-Lozano, J. M.; Galera-Cusí, A.; Julibert, A.; Ruiz-Canela, M.; Martinez-Lacruz, R.; Pérez-Vega, K.-A.; Galmes-Panades, A. M.; Pastor-Polo, C.; Moreno-Rodriguez, A.; Gea, A.; Fitó, M.; Lamuela-Raventós, R. M.; Salas-Salvadó, J. Associations between Dietary Polyphenols and Type 2 Diabetes in a Cross-Sectional Analysis of the PREDIMED-Plus Trial: Role of Body Mass Index and Sex. Antioxidants 2019, 8 (11), 537,  DOI: 10.3390/antiox8110537
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    Associations between dietary polyphenols and type 2 diabetes in a cross-sectional analysis of the PREDIMED-plus trial: role of body mass index and sex
    Tresserra-Rimbau, Anna; Castro-Barquero, Sara; Vitelli-Storelli, Facundo; Becerra-Tomas, Nerea; Vazquez-Ruiz, Zenaida; Diaz-Lopez, Andres; Corella, Dolores; Castaner, Olga; Romaguera, Dora; Vioque, Jesus; Alonso-Gomez, Angel Maria; Waernberg, Julia; Martinez, Jose Alfredo; Serra-Majem, Lluis; Estruch, Ramon; Tinahones, Francisco Jose; Lapetra, Jose; Pinto, Xavier; Tur, Josep Antoni; Lopez-Miranda, Jose; Garcia-Molina, Laura; Delgado-Rodriguez, Miguel; Matia-Martin, Pilar; Daimiel, Lidia; Rubin-Garcia, Maria; Vidal, Josep; Galdon, Alba; Ros, Emilio; Basterra-Gortari, Francisco Javier; Babio, Nancy; Sorli, Jose Vicente; Hernaez, Alvaro; Konieczna, Jadwiga; Notario-Barandiaran, Leyre; Tojal-Sierra, Lucas; Perez-Lopez, Jessica; Abete, Itziar; Alvarez-Perez, Jacqueline; Fernandez-Garcia, Jose Carlos; Santos-Lozano, Jose Manuel; Galera-Cusi, Ana; Julibert, Alicia; Ruiz-Canela, Miguel; Martinez-Lacruz, Raul; Perez-Vega, Karla-Alejandra; Galmes-Panades, Aina Maria; Pastor-Polo, Concepcion; Moreno-Rodriguez, Anai; Gea, Alfredo; Fito, Montserrat; Lamuela-Raventos, Rosa Maria; Salas-Salvado, Jordi
    Antioxidants (2019), 8 (11), 537CODEN: ANTIGE; ISSN:2076-3921. (MDPI AG)
    Overweight and obesity are important risk factors for type 2 diabetes (T2D). Moving towards healthier diets, namely, diets rich in bioactive compds., could decrease the odds of suffering T2D. However, those individuals with high body mass index (BMI) may have altered absorption or metab. of some nutrients and dietary components, including polyphenols. Therefore, we aimed to assess whether high intakes of some classes of polyphenols are assocd. with T2D in a population with metabolic syndrome and how these assocns. depend on BMI and sex. This baseline cross-sectional anal. includes 6633 participants from the PREDIMED-Plus trial. Polyphenol intakes were calcd. from food frequency questionnaires (FFQ). Cox regression models with const. time at risk and robust variance estimators were used to est. the prevalence ratios (PRs) for polyphenol intake and T2D prevalence using the lowest quartile as the ref. group. Analyses were stratified by sex and BMI groups (overweight and obese) to evaluate potential effect modification. Catechins, proanthocyanidins, hydroxybenzoic acids, and lignans were inversely assocd. with T2D. Hydroxycinnamic acids were directly related in men. These assocns. were different depending on sex and BMI, i.e., women and overweight obtained stronger inverse assocns.
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    Lordan, R.; Tsoupras, A.; Zabetakis, I. Platelet activation and prothrombotic mediators at the nexus of inflammation and atherosclerosis: Potential role of antiplatelet agents. Blood Rev. 2021, 45, 100694,  DOI: 10.1016/j.blre.2020.100694
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    75
    Platelet activation and prothrombotic mediators at the nexus of inflammation and atherosclerosis: Potential role of antiplatelet agents
    Lordan, Ronan; Tsoupras, Alexandros; Zabetakis, Ioannis
    Blood Reviews (2021), 45 (), 100694CODEN: BLOREB; ISSN:0268-960X. (Elsevier Ltd.)
    A review. Platelets are central to inflammation-related manifestations of cardiovascular diseases (CVD) such as atherosclerosis. Platelet-activating factor (PAF), thrombin, thromboxane A2 (TxA2), and ADP are some of the key agonists of platelet activation that are at the intersection between a plethora of inflammatory pathways that modulate pro-inflammatory and coagulation processes. The aim of this article is to review the role of platelets and the relationship between their structure, function, and the interactions of their constituents in systemic inflammation and atherosclerosis. Antiplatelet therapies are discussed with a view to primary prevention of CVD by the clin. redn. of platelet reactivity and inflammation. Current antiplatelet therapies are effective in reducing cardiovascular risk but increase bleeding risk. Novel therapeutic antiplatelet approaches beyond current pharmacol. modalities that do not increase the risk of bleeding require further investigation. There is potential for specifically designed nutraceuticals that may become safer alternatives to pharmacol. antiplatelet agents for the primary prevention of CVD but there is serious concern over their efficacy and regulation, which requires considerably more research.
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    Demrow, H. S.; Slane, P. R.; Folts, J. D. Administration of wine and grape juice inhibits in vivo platelet activity and thrombosis in stenosed canine coronary arteries. Circulation 1995, 91 (4), 1182– 8,  DOI: 10.1161/01.CIR.91.4.1182
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    Administration of wine and grape juice inhibits in vivo platelet activity and thrombosis in stenosed canine coronary arteries
    Demrow H S; Slane P R; Folts J D
    Circulation (1995), 91 (4), 1182-8 ISSN:0009-7322.
    BACKGROUND: Moderate daily consumption of alcoholic beverages is a negative risk factor for the development of atherosclerosis and coronary artery disease (CAD), especially in France and other Mediterranean areas where red wine is regularly consumed with meals. Platelets contribute to the development of atherosclerosis, CAD, and acute arterial thrombus formation. METHODS AND RESULTS: Anesthetized dogs were prepared with the Folts model of mechanically stenosed coronary arteries and intimal damage. Periodic acute platelet-mediated thrombus formation occurred, causing cyclic flow reductions (CFRs) in coronary blood flow. The CFRs were eliminated by the administration of 1.62 +/- 1.12 mL/kg red wine intravenously (IV) and 4.0 mL/kg intragastrically (IG). The CFRs were abolished by 2.04 +/- 1.42 mL/kg of grape juice IV and 10 mL/kg IG. White wine did not have significant results in eliminating the CFRs, either IV (2.0 mL/kg) or IG (4.0 mL/kg), decreasing the slopes of the CFRs only slightly. CONCLUSIONS: Pure ethanol has been shown to inhibit platelet aggregation in vitro, ex vivo, and in vivo, although a blood alcohol content (BAC) of > or = 0.2 g/dL is usually required. The BAC of dogs administered the red wine-saline solution intravenously was 0.028 g/dL, much less than is usually necessary for platelet inhibition with pure ethanol. Because red wine and grape juice, but not white wine, abolished the CFRs, this suggests there are compounds present in red wine and grape juice that are not present or are present in a lower concentration in white wine. Wine and grape juice contain a wide variety of naturally occurring compounds, including fungicides, tannins, anthocyanins, and phenolic flavonoids (including flavonols and flavones). These compounds have shown platelet inhibition in vitro by a variety of proposed mechanisms. Perhaps the biological activity of these compounds can explain the platelet-inhibitory properties of red wine and grape juice that are observed without high levels of ethanol.
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    Keevil, J. G.; Osman, H. E.; Reed, J. D.; Folts, J. D. Grape Juice, But Not Orange Juice or Grapefruit Juice, Inhibits Human Platelet Aggregation. Journal of Nutrition 2000, 130 (1), 53– 56,  DOI: 10.1093/jn/130.1.53
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    77
    Grape juice, but not orange juice or grapefruit juice, inhibits human platelet aggregation
    Keevil, Jon G.; Osman, Hashim E.; Reed, Jess D.; Folts, John D.
    Journal of Nutrition (2000), 130 (1), 53-56CODEN: JONUAI; ISSN:0022-3166. (American Society for Nutritional Sciences)
    Blood platelets are involved in atherosclerosis development and decreasing the platelet activity by medication decreases the incidence and severity of the disease. Red wine and grapes contain polyphenolic compds., including flavonoids, which can decrease platelet aggregation and have been assocd. with lower rates of cardiovascular disease. Citrus fruits contain different classes of polyphenols that may not share the same properties. This study evaluated whether com. grape, orange, and grapefruit juices taken daily decrease the ex vivo platelet activity. Ten healthy humans (5 men, 5 women; ages 26-58 yr) drank 5-7.5 mL/kg/day of purple grape juice, orange juice, or grapefruit juice for 7-10 days each. The platelet aggregation was detd. by whole blood impedance aggregometry at baseline and after consumption of each juice. Drinking purple grape juice for 1 wk decreased the whole blood platelet aggregation response to 1 mg collagen/L by 77% (from 17.9±2.3 to 4.0±6.8 Ω). Orange juice and grapefruit juice had no effect on platelet aggregation. The purple grape juice had ∼3-times the total polyphenolic concn. of the citrus juices and was a potent platelet inhibitor in healthy subjects while the citrus juices showed no effect. The platelet inhibitory effect of the flavonoids in grape juice may decrease the risk of coronary thrombosis and myocardial infarction.
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    Hamburg, N. M.; Palmisano, J.; Larson, M. G.; Sullivan, L. M.; Lehman, B. T.; Vasan, R. S.; Levy, D.; Mitchell, G. F.; Vita, J. A.; Benjamin, E. J. Relation of Brachial and Digital Measures of Vascular Function in the Community. Hypertension 2011, 57 (3), 390– 396,  DOI: 10.1161/HYPERTENSIONAHA.110.160812
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    Relation of brachial and digital measures of vascular function in the community: The Framingham Heart Study
    Hamburg, Naomi M.; Palmisano, Joseph; Larson, Martin G.; Sullivan, Lisa M.; Lehman, Birgitta T.; Vasan, Ramachandran S.; Levy, Daniel; Mitchell, Gary F.; Vita, Joseph A.; Benjamin, Emelia J.
    Hypertension (2011), 57 (3), 390-396CODEN: HPRTDN; ISSN:0194-911X. (Lippincott Williams & Wilkins)
    Impaired vascular function contributes to the development of clin. cardiovascular disease. The relation between vasodilator function assessed noninvasively in the brachial and digital arteries remains incompletely defined. In the Framingham Offspring, Third Generation and Omni Cohorts, we measured flow-mediated dilation (FMD; n=7031; age 48±13 years; age range, 19 to 88 years; 54% women) and peripheral arterial tonometry (PAT) ratio (n=4352; 55±16 years; age range, 19 to 90 years; 51% women). Abnormal vascular function for each measure was defined by the sex-specific fifth percentile in a ref. group free of conventional cardiovascular risk factors. The prevalence of abnormal FMD but not abnormal PAT ratio was higher with advancing age. In multivariable models, higher body mass index was assocd. with a higher prevalence of both abnormal FMD and PAT ratio. Addnl. correlates of abnormal FMD included increasing age and higher systolic blood pressure. In contrast, correlates of abnormal PAT ratio included lower systolic blood pressure, increasing total/high-d. lipoprotein cholesterol ratio, diabetes, smoking, and lipid-lowering medication. Whereas women had higher FMD and PAT ratios compared with men, using sex-specific ref. values, women had a higher prevalence of abnormal brachial and digital vascular function. In participants who had concurrent testing (n=1843), PAT ratio was not significantly assocd. with FMD in multivariable models. In this large, community-based cohort, brachial and digital measures of vascular function had differing relations with cardiovascular risk factors and were nearly uncorrelated with each other. These results suggest that FMD and PAT provide distinct information regarding vascular function in conduit vs. smaller digital vessels.
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    Stein, J. H.; Keevil, J. G.; Wiebe, D. A.; Aeschlimann, S.; Folts, J. D. Purple Grape Juice Improves Endothelial Function and Reduces the Susceptibility of LDL Cholesterol to Oxidation in Patients With Coronary Artery Disease. Circulation 1999, 100 (10), 1050– 1055,  DOI: 10.1161/01.CIR.100.10.1050
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    Purple grape juice improves endothelial function and reduces the susceptibility of LDL cholesterol to oxidation in patients with coronary artery disease
    Stein J H; Keevil J G; Wiebe D A; Aeschlimann S; Folts J D
    Circulation (1999), 100 (10), 1050-5 ISSN:.
    BACKGROUND: In vitro, the flavonoid components of red wine and purple grape juice are powerful antioxidants that induce endothelium-dependent vasodilation of vascular rings derived from rat aortas and human coronary arteries. Although improved endothelial function and inhibition of LDL oxidation may be potential mechanisms by which red wine and flavonoids reduce cardiovascular risk, the in vivo effects of grape products on endothelial function and LDL oxidation have not been investigated. This study assessed the effects of ingesting purple grape juice on endothelial function and LDL susceptibility to oxidation in patients with coronary artery disease (CAD). METHODS AND RESULTS: Fifteen adults with angiographically documented CAD ingested 7.7+/-1.2 mL. kg(-1). d(-1) of purple grape juice for 14 days. Flow-mediated vasodilation (FMD) was measured using high-resolution brachial artery ultrasonography. Susceptibility of LDL particles to oxidation was determined from the rate of conjugated diene formation after exposure to copper chloride. At baseline, FMD was impaired (2.2+/-2. 9%). After ingestion of grape juice, FMD increased to 6.4+/-4.7% (P=0.003). In a linear regression model that included age, artery diameter, lipid values, and use of lipid-lowering and antioxidant therapies, the effect of grape juice on FMD remained significant (mean change 4.2+/-4.4%, P<0.001). After ingestion of grape juice, lag time increased by 34.5% (P=0.015). CONCLUSIONS: Short-term ingestion of purple grape juice improves FMD and reduces LDL susceptibility to oxidation in CAD patients. Improved endothelium-dependent vasodilation and prevention of LDL oxidation are potential mechanisms by which flavonoids in purple grape products may prevent cardiovascular events, independent of alcohol content.
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    Sun, Y.; Zimmermann, D.; De Castro, C. A.; Actis-Goretta, L. Dose-response relationship between cocoa flavanols and human endothelial function: a systematic review and meta-analysis of randomized trials. Food Funct 2019, 10 (10), 6322– 6330,  DOI: 10.1039/C9FO01747J
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    80
    Dose-response relationship between cocoa flavanols and human endothelial function: a systematic review and meta-analysis of randomized trials
    Sun, Ye; Zimmermann, Diane; De Castro, Carlos Antonio; Actis-Goretta, Lucas
    Food & Function (2019), 10 (10), 6322-6330CODEN: FFOUAI; ISSN:2042-6496. (Royal Society of Chemistry)
    Several intervention studies have investigated the relationship between cocoa flavanols and endothelial function. However, the shape of the assocn. and the type of compds. responsible for the effects are largely unknown. To examine the dose-response assocn. between the consumption of cocoa flavanols and endothelial function, measured by flow-mediated dilation (FMD). Two investigators searched Scopus for the relevant human intervention studies, which were pooled and meta-analyzed. Heterogeneity in the findings was explored with various subgroup analyses. Fifteen published articles with 18 intervention arms met the inclusion criteria. Participants in these intervention groups received 80 to 1248 mg (mean: 704 mg) more flavanols than control groups. A significant improvement of FMD by 1.17% (95% CI: 0.76% to 1.57%) was calcd., with strong evidence of a non-linear assocn. (inverted U-shape) between cocoa flavanols and FMD. This meta-anal. provides evidence that cocoa flavanols could significantly improve endothelial function, with an optimal effect obsd. with 710 mg total flavanols, 95 mg (-)-epicatechin or 25 mg (+)-catechin. However, there was substantial variation in the results that could not be explained by the characteristics that we explored, and there were significant risk-of-bias concerns with a large majority of the studies.
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    Schroeter, H.; Heiss, C.; Balzer, J.; Kleinbongard, P.; Keen, C. L.; Hollenberg, N. K.; Sies, H.; Kwik-Uribe, C.; Schmitz, H. H.; Kelm, M. (−)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans. Proc. Natl. Acad. Sci. U. S. A. 2006, 103 (4), 1024– 9,  DOI: 10.1073/pnas.0510168103
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    81
    (-)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans
    Schroeter, Hagen; Heiss, Christian; Balzer, Jan; Kleinbongard, Petra; Keen, Carl L.; Hollenberg, Norman K.; Sies, Helmut; Kwik-Uribe, Catherine; Schmitz, Harold H.; Kelm, Malte
    Proceedings of the National Academy of Sciences of the United States of America (2006), 103 (4), 1024-1029CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)
    Epidemiol. and medical anthropol. studies suggest that flavanol-rich foods can have cardiovascular health benefits. Endothelial dysfunction, a prognostically relevant key event in atherosclerosis, is characterized by decreased bioactivity of nitric oxide (NO) and impaired flow-mediated vasodilation (FMD). Ingestion of flavanol-rich cocoa in 16 healthy men (25-32 yr) was assocd. with acute elevation in the levels of circulating NO species, enhanced FMD response of conduit arteries, and augmented microcirculation. The concns. and chem. profiles of circulating flavanol metabolites were detd. and multivariate regression anal. identified (-)-epicatechin and its metabolite epicatechin-7-O-glucuronide as independent predictors of the vascular effects of the flavanol-rich cocoa ingestion. A mixt. of flavanols/metabolites resembling the profile and concn. of circulating flavanol compds. in blood plasma after cocoa ingestion also induced relaxation in preconstricted rabbit aortic rings ex vivo, thus mimicking the acetylcholine-induced relaxations. Ex vivo flavanol-induced relaxation and the in vivo increases in FMD were abolished by inhibition of NO synthase. Oral administration of pure (-)-epicatechin to humans closely emulated acute vascular effects of flavanol-rich cocoa. The concept that chronic intake of high-flavanol diets is assocd. with prolonged, augmented NO biosynthesis is supported by data that indicate a correlation between the chronic consumption of cocoa flavanol-rich diet and augmented urinary excretion of NO metabolites. Thus, ingestion of the (-)-epicatechin flavanol can be causally linked to reported vascular effects of consuming flavanol-rich cocoa.
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    Alañón, M. E.; Castle, S. M.; Serra, G.; Lévèques, A.; Poquet, L.; Actis-Goretta, L.; Spencer, J. P. E. Acute study of dose-dependent effects of (−)-epicatechin on vascular function in healthy male volunteers: A randomized controlled trial. Clinical Nutrition 2020, 39 (3), 746– 754,  DOI: 10.1016/j.clnu.2019.03.041
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    82
    Acute study of dose-dependent effects of (-)-epicatechin on vascular function in healthy male volunteers: A randomized controlled trial
    Alanon, M. E.; Castle, S. M.; Serra, G.; Leveques, A.; Poquet, L.; Actis-Goretta, L.; Spencer, J. P. E.
    Clinical Nutrition (2020), 39 (3), 746-754CODEN: CLNUDP; ISSN:0261-5614. (Elsevier Ltd.)
    The current study examd. the dose-dependent effects of (-)-epicatechin on human vascular function with concurrent measurement of plasma (-)-epicatechin metabolites and levels of circulating nitrite and nitrate species, NOx.An acute, double-blind, placebo-controlled, crossover intervention trial was conducted in 20 healthy males with 4 treatment arms: water-based (-)-epicatechin (0.1, 0.5 and 1.0 mg/kg BW) and a water only as control. Vascular function was assessed by flow-mediated dilatation (FMD) measured at the brachial artery, laser Doppler imaging with iontophoresis (LDI) at the s.c. capillaries of the forearm (response to Ach and SNP) and peripheral blood pressure (BP) at baseline, 1, 2, 4 and 6 h post-intervention. Plasma anal. of epicatechin metabolites was conducted by LC-MS and circulating plasma of nitrite and nitrate species were performed using an HPLC-based system (ENO-30).Significant increases in % FMD were found to occur at 1 and 2 h following intake of 1 mg/kg BW, and at 2 h for the 0.5 mg/kg BW intake. Non-significant changes in circulating NOx was obsd.Our data add further evidence that (-)-epicatechin is a causal vasoactive mol. within flavanol-contg. foods/beverages. In addn., we show for the first time that intake levels as low as 0.5 mg/kg BW are capable of inducing acute improvements in vascular function (FMD) in healthy volunteers.
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  83. 83
    Sansone, R.; Ottaviani, J. I.; Rodriguez-Mateos, A.; Heinen, Y.; Noske, D.; Spencer, J. P.; Crozier, A.; Merx, M. W.; Kelm, M.; Schroeter, H.; Heiss, C. Methylxanthines enhance the effects of cocoa flavanols on cardiovascular function: randomized, double-masked controlled studies. American Journal of Clinical Nutrition 2017, 105 (2), 352– 360,  DOI: 10.3945/ajcn.116.140046
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    83
    Methylxanthines enhance the effects of cocoa flavanols on cardiovascular function: randomized, double-masked controlled studies
    Sansone, Roberto; Ottaviani, Javier I.; Rodriguez-Mateos, Ana; Heinen, Yvonne; Noske, Dorina; Spencer, Jeremy P.; Crozier, Alan; Merx, Marc W.; Kelm, Malte; Schroeter, Hagen; Heiss, Christian
    American Journal of Clinical Nutrition (2017), 105 (2), 352-360CODEN: AJCNAC; ISSN:1938-3207. (American Society for Nutrition)
    Background: Cocoa flavanol intake, esp. that of (-)-epicatechin, has been linked to beneficial effects on human cardiovascular function. However, cocoa also contains the methylxanthines theobromine and caffeine, which may also affect vascular function. Objective: We sought to det. whether an interaction between cocoa flavanols and methylxanthines exists that influences cocoa flavanol-dependent vascular effects. Design: Test drinks that contained various amts. of cocoa flavanols (0-820 mg) and methylxanthines (0-220 mg), either together or individually, were consumed by healthy volunteers (n = 47) in 4 different clin. studies-3 with a randomized, double-masked crossover design and 1 with 4 parallel crossover studies. Vascular status was assessed by measuring flow-mediated vasodilation (FMD), brachial pulse wave velocity (bPWV), circulating angiogenic cells (CACs), and blood pressure before and 2 h after the ingestion of test drinks. Results: Although cocoa flavanol intake increased FMD 2 h after intake, the consumption of cocoa flavanols with methylxanthines resulted in a greater enhancement of FMD. Methylxanthine intake alone did not result in statistically significant changes in FMD. Cocoa flavanol ingestion alone decreased bPWVand diastolic blood pressure and increased CACs. Each of these changes was more pronounced when cocoa flavanols and methylxanthines were ingested together. It is important to note that the area under the curve of the plasma concn. of (-)-epicatechin metabolites over time was higher after the co-ingestion of cocoa flavanols and methylxanthines than after the intake of cocoa flavanols alone. Similar results were obtained when pure (-)-epicatechin and the methylxanthines theobromine and caffeine were consumed together. Conclusion: A substantial interaction between cocoa flavanols and methylxanthines exists at the level of absorption, in which the methylxanthines mediate an increased plasma concn. of (-)-epicatechin metabolites that coincides with enhanced vascular effects commonly ascribed to cocoa flavanol intake.
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  84. 84
    Estruch, R.; Ros, E.; Salas-Salvado, J.; Covas, M. I.; Corella, D.; Aros, F.; Gomez-Gracia, E.; Ruiz-Gutierrez, V.; Fiol, M.; Lapetra, J.; Lamuela-Raventos, R. M.; Serra-Majem, L.; Pinto, X.; Basora, J.; Munoz, M. A.; Sorli, J. V.; Martinez, J. A.; Fito, M.; Gea, A.; Hernan, M. A.; Martinez-Gonzalez, M. A.; PREDIMED Study Investigators Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts. N Engl J. Med. 2018, 378 (25), e34,  DOI: 10.1056/NEJMoa1800389
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    84
    Primary prevention of cardiovascular disease with a Mediterranean diet supplemented with extra-virgin olive oil or nuts
    Estruch, R.; Ros, E.; Salas-Salvado, J.; Covas, M.-I.; Corella, D.; Aros, F.; Gomez-Gracia, E.; Ruiz-Gutierrez, V.; Fiol, M.; Lapetra, J.; Lamuela-Raventos, R. M.; Serra-Majem, L.; Pinto, X.; Basora, J.; Munoz, M. A.; Sorli, J. V.; Martinez, J. A.; Fito, M.; Gea, A.; Hernan, M. A.; Martinez-Gonzalez, M. A.
    New England Journal of Medicine (2018), 378 (25), e34-e47CODEN: NEJMAG; ISSN:1533-4406. (Massachusetts Medical Society)
    Background Observational cohort studies and a secondary prevention trial have shown inverse assocns. between adherence to the Mediterranean diet and cardiovascular risk. Methods In a multicenter trial in Spain, we assigned 7447 participants (55 to 80 years of age, 57% women) who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly educational sessions and, depending on group assignment, free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was a major cardiovascular event (myocardial infarction, stroke, or death from cardiovascular causes). After a median follow-up of 4.8 years, the trial was stopped on the basis of a prespecified interim anal. In 2013, we reported the results for the primary end point in the Journal. We subsequently identified protocol deviations, including enrollment of household members without randomization, assignment to a study group without randomization of some participants at 1 of 11 study sites, and apparent inconsistent use of randomization tables at another site. We have withdrawn our previously published report and now report revised effect ests. based on analyses that do not rely exclusively on the assumption that all the participants were randomly assigned. Results A primary end-point event occurred in 288 participants; there were 96 events in the group assigned to a Mediterranean diet with extra-virgin olive oil (3.8%), 83 in the group assigned to a Mediterranean diet with nuts (3.4%), and 109 in the control group (4.4%). In the intention-to-treat anal. including all the participants and adjusting for baseline characteristics and propensity scores, the hazard ratio was 0.69 (95% confidence interval [CI], 0.53 to 0.91) for a Mediterranean diet with extra-virgin olive oil and 0.72 (95% CI, 0.54 to 0.95) for a Mediterranean diet with nuts, as compared with the control diet. Results were similar after the omission of 1588 participants whose study-group assignments were known or suspected to have departed from the protocol. conclusions In this study involving persons at high cardiovascular risk, the incidence of major cardiovascular events was lower among those assigned to a Mediterranean diet supplemented with extra-virgin olive oil or nuts than among those assigned to a reduced-fat diet.
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  85. 85
    Heiss, C.; Jahn, S.; Taylor, M.; Real, W. M.; Angeli, F. S.; Wong, M. L.; Amabile, N.; Prasad, M.; Rassaf, T.; Ottaviani, J. I.; Mihardja, S.; Keen, C. L.; Springer, M. L.; Boyle, A.; Grossman, W.; Glantz, S. A.; Schroeter, H.; Yeghiazarians, Y. Improvement of endothelial function with dietary flavanols is associated with mobilization of circulating angiogenic cells in patients with coronary artery disease. J. Am. Coll Cardiol 2010, 56 (3), 218– 24,  DOI: 10.1016/j.jacc.2010.03.039
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    85
    Improvement of endothelial function with dietary flavanols is associated with mobilization of circulating angiogenic cells in patients with coronary artery disease
    Heiss, Christian; Jahn, Sarah; Taylor, Melanie; Real, Wendy May; Angeli, Franca S.; Wong, Maelene L.; Amabile, Nicolas; Prasad, Megha; Rassaf, Tienush; Ottaviani, Javier I.; Mihardja, Shirley; Keen, Carl L.; Springer, Matthew L.; Boyle, Andrew; Grossman, William; Glantz, Stanton A.; Schroeter, Hagen; Yeghiazarians, Yerem
    Journal of the American College of Cardiology (2010), 56 (3), 218-224CODEN: JACCDI; ISSN:0735-1097. (Elsevier Inc.)
    In patients with coronary artery disease (CAD) medically managed according to currently accepted guidelines, we tested whether a 1-mo dietary intervention with flavanol-contg. cocoa leads to an improvement of endothelial dysfunction and whether this is assocd. with an enhanced no. and function of circulating angiogenic cells (CACs). Dietary flavanols can improve endothelial dysfunction. The CACs, also termed endothelial progenitor cells, are crit. for vascular repair and maintenance of endothelial function. In a randomized, controlled, double-masked, cross-over trial, 16 CAD patients (64 ± 3 years of age) received a dietary high-flavanol intervention (HiFI [375 mg]) and a macronutrient- and micronutrient-matched low-flavanol intervention (LoFI [9 mg]) twice daily in random order over 30 days. Endothelium-dependent vasomotor function, as measured by flow-mediated vasodilation of the brachial artery, improved by 47% in the HiFI period compared with the LoFI period. After HiFI, the no. of CD34+/KDR+-CACs, as measured by flow cytometry, increased 2.2-fold as compared with after LoFI. The CAC functions, as measured by the capacity to survive, differentiate, proliferate, and to migrate were not different between the groups. The HiFI led to a decrease in systolic blood pressure (mean change over LoFI: -4.2 ± 2.7 mm Hg), and increase in plasma nitrite level (mean change over LoFI: 74 ± 32 nM). Applying a mixed-effects linear regression model, the results demonstrated a significant increase In flow-mediated vasodilation and a decrease In systolic blood pressure with increasing levels of CD34+/KDR+-CACs. Sustained Improvements in endothelial dysfunction by regular dietary Intake of flavanols are assocd. with mobilization of functional CACs.
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  86. 86
    Lorenz, M.; Rauhut, F.; Hofer, C.; Gwosc, S.; Müller, E.; Praeger, D.; Zimmermann, B. F.; Wernecke, K.-D.; Baumann, G.; Stangl, K.; Stangl, V. Tea-induced improvement of endothelial function in humans: No role for epigallocatechin gallate (EGCG). Sci. Rep. 2017, 7 (1), 2279,  DOI: 10.1038/s41598-017-02384-x
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    86
    Tea-induced improvement of endothelial function in humans: No role for epigallocatechin gallate (EGCG)
    Lorenz Mario; Rauhut Franziska; Hofer Christine; Gwosc Stefanie; Muller Eda; Praeger Damaris; Baumann Gert; Stangl Verena; Lorenz Mario; Stangl Verena; Zimmermann Benno F; Zimmermann Benno F; Wernecke Klaus-Dieter; Stangl Karl
    Scientific reports (2017), 7 (1), 2279 ISSN:.
    Consumption of tea is inversely associated with cardiovascular diseases. However, the active compound(s) responsible for the protective effects of tea are unknown. Although many favorable cardiovascular effects in vitro are mediated by epigallocatechin gallate (EGCG), its contribution to the beneficial effects of tea in vivo remains unresolved. In a randomised crossover study, a single dose of 200 mg EGCG was applied in three different formulas (as green tea beverage, green tea extract (GTE), and isolated EGCG) to 50 healthy men. Flow-mediated dilation (FMD) and endothelial-independent nitro-mediated dilation (NMD) was measured before and two hours after ingestion. Plasma levels of tea compounds were determined after each intervention and correlated with FMD. FMD significantly improved after consumption of green tea containing 200 mg EGCG (p < 0.01). However, GTE and EGCG had no significant effect on FMD. NMD did not significantly differ between interventions. EGCG plasma levels were highest after administration of EGCG and lowest after consumption of green tea. Plasma levels of caffeine increased after green tea consumption. The results show that EGCG is most likely not involved in improvement of flow-mediated dilation by green tea. Instead, other tea compounds, metabolites or combinations thereof may play a role.
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    Gu, L.; Gonzalez, F. J.; Kalow, W.; Tang, B. K. Biotransformation of caffeine, paraxanthine, theobromine and theophylline by cDNA-expressed human CYP1A2 and CYP2E1. Pharmacogenetics and Genomics 1992, 2 (2), 73,  DOI: 10.1097/00008571-199204000-00004
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    Martínez-Pinilla, E.; Oñatibia-Astibia, A.; Franco, R. The relevance of theobromine for the beneficial effects of cocoa consumption. Front. Pharmacol. 2015, 6, 30,  DOI: 10.3389/fphar.2015.00030
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    88
    The relevance of theobromine for the beneficial effects of cocoa consumption
    Martinez-Pinilla Eva; Onatibia-Astibia Ainhoa; Franco Rafael
    Frontiers in pharmacology (2015), 6 (), 30 ISSN:1663-9812.
    Cocoa consumption began in America and in the mid sixteenth Century it quickly spread to Europe. Beyond being considered a pleasant habit due to its rich sweet lingering taste, chocolate was considered a good nutrient and even a medicine. Traditionally, health benefits of cocoa have been related with the high content of antioxidants of Theobroma cocoa beans. However, the direct psychoactive effect due to methylxanthines in cocoa is notable. Theobromine and caffeine, in the proportions found in cocoa, are responsible for the liking of the food/beverage. These compounds influence in a positive way our moods and our state of alertness. Theobromine, which is found in higher amounts than caffeine, seems to be behind several effects attributed to cocoa intake. The main mechanisms of action are inhibition of phosphodiesterases and blockade of adenosine receptors. Further mechanisms are being explored to better understand the health benefits associated to theobromine consumption. Unlike what happens in other mammals -pets- included, theobromine is safe for humans and has fewer unwanted effects than caffeine. Therefore, theobromine deserves attention as one of the most attractive molecules in cocoa.
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    Golshiri, K.; Ataei Ataabadi, E.; Portilla Fernandez, E. C.; Jan Danser, A. H.; Roks, A. J. M. The importance of the nitric oxide-cGMP pathway in age-related cardiovascular disease: Focus on phosphodiesterase-1 and soluble guanylate cyclase. Basic & Clinical Pharmacology & Toxicology 2020, 127 (2), 67– 80,  DOI: 10.1111/bcpt.13319
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    89
    The importance of the nitric oxide-cGMP pathway in age-related cardiovascular disease: Focus on phosphodiesterase-1 and soluble guanylate cyclase
    Golshiri, Keivan; Ataei Ataabadi, Ehsan; Portilla Fernandez, Eliana C.; Jan Danser, A. H.; Roks, Anton J. M.
    Basic & Clinical Pharmacology & Toxicology (2020), 127 (2), 67-80CODEN: BCPTBO; ISSN:1742-7835. (Wiley-Blackwell)
    A review. Among ageing-related illnesses, cardiovascular disease (CVD) remains the leading cause of morbidity and mortality causing one-third of all deaths worldwide. Ageing evokes a no. of functional, pharmacol. and morphol. changes in the vasculature, accompanied by a progressive failure of protective and homeostatic mechanisms, resulting in target organ damage. Impaired vasomotor, proliferation, migration, antithrombotic and anti-inflammatory function in both the endothelial and vascular smooth muscle cells are parts of the vascular ageing phenotype. The endothelium regulates these functions by the release of a wide variety of active mols. including endothelium-derived relaxing factors such as nitric oxide, prostacyclin (PGI2) and endothelium-derived hyperpolarization (EDH). During ageing, a functional decay of the nitric oxide pathway takes place. Nitric oxide signals to VSMC and other important cell types for vascular homeostasis through the second messenger cyclic guanosine monophosphate (cGMP). Maintenance of proper cGMP levels is an important goal in sustainment of proper vascular function during ageing. For this purpose, different components can be targeted in this signalling system, and among them, phosphodiesterase-1 (PDE1) and sol. guanylate cyclase (sGC) are crucial. This review focuses on the role of PDE1 and sGC in conditions that are relevant for vascular ageing.
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    Granda, H.; de Pascual-Teresa, S. Interaction of Polyphenols with Other Food Components as a Means for Their Neurological Health Benefits. J. Agric. Food Chem. 2018, 66 (31), 8224– 8230,  DOI: 10.1021/acs.jafc.8b02839
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    90
    Interaction of Polyphenols with Other Food Components as a Means for Their Neurological Health Benefits
    Granda Hugo; de Pascual-Teresa Sonia
    Journal of agricultural and food chemistry (2018), 66 (31), 8224-8230 ISSN:.
    Over the last few years, there has been increasing interest in the possible beneficial effect of polyphenol consumption on neurodegenerative disorders. Because there is a clear impact of environmental factors on the onset and evolution of neurodegenerative conditions, food arises as a promising factor that might be influencing this group of pathologies. The mechanisms by which polyphenols can affect these processes can be through direct interaction with redox signaling or inflammatory pathways but can also be explained by the interaction of dietary polyphenols with either micro- and macronutrients that are known to have neurological effects or interaction with food contaminants or food-associated toxins, avoiding their neuronal toxicity.
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  91. 91
    Rodriguez-Mateos, A.; Hezel, M.; Aydin, H.; Kelm, M.; Lundberg, J. O.; Weitzberg, E.; Spencer, J. P. E.; Heiss, C. Interactions between cocoa flavanols and inorganic nitrate: Additive effects on endothelial function at achievable dietary amounts. Free Radical Biol. Med. 2015, 80, 121– 128,  DOI: 10.1016/j.freeradbiomed.2014.12.009
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    91
    Interactions between cocoa flavanols and inorganic nitrate: Additive effects on endothelial function at achievable dietary amounts
    Rodriguez-Mateos, Ana; Hezel, Michael; Aydin, Hilal; Kelm, Malte; Lundberg, Jon O.; Weitzberg, Eddie; Spencer, Jeremy P. E.; Heiss, Christian
    Free Radical Biology & Medicine (2015), 80 (), 121-128CODEN: FRBMEH; ISSN:0891-5849. (Elsevier B.V.)
    Dietary intervention studies have shown that flavanols and inorg. nitrate can improve vascular function, suggesting that these two bioactives may be responsible for beneficial health effects of diets rich in fruits and vegetables. We aimed to study interactions between cocoa flavanols (CF) and nitrate, focusing on absorption, bioavailability, excretion, and efficacy to increase endothelial function. In a double-blind randomized, dose-response crossover study, flow-mediated dilation (FMD) was measured in 15 healthy subjects before and at 1, 2, 3, and 4 h after consumption of CF (1.4-10.9 mg/kg bw) or nitrate (0.1-10 mg/kg bw). To study flavanol-nitrate interactions, an addnl. intervention trial was performed with nitrate and CF taken in sequence at low and high amts. FMD was measured before (0 h) and at 1 h after ingestion of nitrate (3 or 8.5 mg/kg bw) or water. Then subjects received a CF drink (2.7 or 10.9 mg/kg bw) or a micro- and macronutrient-matched CF-free drink. FMD was measured at 1, 2, and 4 h thereafter. Blood and urine samples were collected and assessed for CF and nitric oxide (NO) metabolites with HPLC and gas-phase reductive chemiluminescence. Finally, intragastric formation of NO after CF and nitrate consumption was investigated. Both CF and nitrate induced similar intake-dependent increases in FMD. Maximal values were achieved at 1 h postingestion and gradually decreased to reach baseline values at 4 h. These effects were additive at low intake levels, whereas CF did not further increase FMD after high nitrate intake. Nitrate did not affect flavanol absorption, bioavailability, or excretion, but CF enhanced nitrate-related gastric NO formation and attenuated the increase in plasma nitrite after nitrate intake. Both flavanols and inorg. nitrate can improve endothelial function in healthy subjects at intake amts. that are achievable with a normal diet. Even low dietary intake of these bioactives may exert relevant effects on endothelial function when ingested together.
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  92. 92
    Siasos, G.; Tousoulis, D.; Kokkou, E.; Oikonomou, E.; Kollia, M.-E.; Verveniotis, A.; Gouliopoulos, N.; Zisimos, K.; Plastiras, A.; Maniatis, K.; Stefanadis, C. Favorable Effects of Concord Grape Juice on Endothelial Function and Arterial Stiffness in Healthy Smokers. American Journal of Hypertension 2014, 27 (1), 38– 45,  DOI: 10.1093/ajh/hpt176
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    Favorable Effects of Concord Grape Juice on Endothelial Function and Arterial Stiffness in Healthy Smokers
    Siasos, Gerasimos; Tousoulis, Dimitris; Kokkou, Eleni; Oikonomou, Evangelos; Kollia, Maria-Eleni; Verveniotis, Aleksis; Gouliopoulos, Nikolaos; Zisimos, Konstantinos; Plastiras, Aris; Maniatis, Konstantinos; Stefanadis, Christodoulos
    American Journal of Hypertension (2014), 27 (1), 38-45CODEN: AJHYE6; ISSN:0895-7061. (Oxford University Press)
    BACKGROUND Smoking is assocd. with impaired vascular function. Concord grape juice (CGJ), a rich source of flavonoids, can modify cardiovascular risk factors. Endothelial function and arterial stiffness are surrogate markers of arterial health. We examd. the impact of CGJ on arterial wall properties in healthy smokers. METHODS We studied the effect of a 2-wk oral treatment with CGJ in 26 healthy smokers on 3 occasions (day 0 (baseline), day 7, and day 14) in a randomized, placebo-controlled, double-blind, crossover study. Measurements were taken before (pSm), immediately after (Sm0), and 20 min after (Sm20) cigarette smoking. Endothelial function was evaluated by flow-mediated dilation (FMD) of the brachial artery. Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness. RESULTS Compared with placebo, treatment with CGJ resulted in a significant improvement in pSm values of FMD (P = 0.02) and PWV (P = 0.04). At baseline, smoking decreased FMD in both the CGJ group (P < 0.001) and the placebo group (P < 0.001). Compared with placebo, CGJ treatment prevented the acute smoking-induced decrease in FMD on day 7 (P = 0.02) and day 14 (P < 0.001). Moreover, at baseline, smoking induced a significant elevation in PWV in both the CGJ group (P = 0.02) and the placebo group (P = 0.04). Treatment with CGJ prevented the smoking-induced elevation in PWV on day 7 (P = 0.003) and day 14 (P < 0.001). CONCLUSIONS CGJ consumption improved endothelial function and vascular elastic properties of the arterial tree in healthy smokers and attenuated acute smoking-induced impairment of arterial wall properties.
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    Coimbra, S.; Lage, S.; Brandizzi, L.; Yoshida, V.; Da Luz, P. L. The action of red wine and purple grape juice on vascular reactivity is independent of plasma lipids in hypercholesterolemic patients. Braz. J. Med. Biol. Res. 2005, 38 (9), 1339– 1347,  DOI: 10.1590/S0100-879X2005000900008
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    93
    The action of red wine and purple grape juice on vascular reactivity is independent of plasma lipids in hypercholesterolemic patients
    Coimbra, S. R.; Lage, S. H.; Brandizzi, L.; Yoshida, V.; da Luz, P. L.
    Brazilian Journal of Medical and Biological Research (2005), 38 (9), 1339-1347CODEN: BJMRDK; ISSN:0100-879X. (Associacao Brasileira de Divulgacao Cientifica)
    Although red wine (RW) reduces cardiovascular risk, the mechanisms underlying the effect have not been identified. Correction of endothelial dysfunction by RW flavonoids could be one mechanism. We measured brachial artery reactivity by high-resoln. ultrasonog., plasma lipids, glucose, adhesion mols. (ICAM-1 and VCAM), and platelet function in 16 hypercholesterolemic individuals (8 men and 8 women; mean age 51.6±8.1 years) without other risk factors. Twenty-four normal subjects were used as controls for vascular reactivity. Subjects randomly received RW, 250 mL/day, or purple grape juice (GJ), 500 mL/day, for 14 days with an equal wash-out period. At baseline, all 16 subjects were hypercholesterolemic (mean LDL = 181.0±28.7 mg/dL) but HDL, triglycerides, glucose, adhesion mols., and platelet function were within normal limits. Brachial artery flow-mediated dilation was significantly decreased compared to controls (9.0±7.1 vs 12.1±4.5%; P < 0.05) and increased with both GJ (10.1±7.1 before vs 16.9±6.7% after: P < 0.05) and RW (10.1±6.4 before vs 15.6±4.6% after; P < 0.05). RW, but not GJ, also significantly increased endothelium-independent vasodilation (17.0±8.6 before vs 23.0±12.0% after; P < 0.01). GJ reduced ICAM-1 but not VCAM and RW had no effect on either mol. No significant alterations were obsd. in plasma lipids, glucose or platelet aggregability with RW or GJ. Both RW and GJ similarly improved flow-mediated dilation, but RW also enhanced endothelium-independent vasodilation in hypercholesterolemic patients despite the increased plasma cholesterol. Thus, we conclude that GJ may protect against coronary artery disease without the addnl. neg. effects of alc. despite the gender.
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    Chou, E. J.; Keevil, J. G.; Aeschlimann, S.; Wiebe, D. A.; Folts, J. D.; Stein, J. H. Effect of ingestion of purple grape juice on endothelial function in patients with coronary heart disease. Am. J. Cardiol 2001, 88 (5), 553– 5,  DOI: 10.1016/S0002-9149(01)01738-6
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    Effect of ingestion or purple grape juice on endothelial function in patients with coronary heart disease
    Chou, Eric J.; Keevil, Jon G.; Aeschlimann, Susan; Wiebe, Donald A.; Folts, John D.; Stein, James H.
    American Journal of Cardiology (2001), 88 (5), 553-555CODEN: AJCDAG; ISSN:0002-9149. (Excerpta Medica, Inc.)
    The endothelial function and antioxidant effects of 2 doses of purple grape juice (GJ), alone or in combination with vitamin E taken orally for 8 wk, were studied in 22 adults with coronary artery disease. Half of the subjects took 8.0 mL GJ/kg in 2 daily portions and the other subjects 4.0 mL GJ/kg in one daily portion. After 28 days, the subjects added 400 IU vitamin E to their daily GJ dose. Endothelial function was evaluated by measuring flow-mediated vasodilation (FMD) of the brachial artery using B-mode ultrasound. Lipid and glucose levels were measured by enzymic techniques. Insulin levels were measured by RIA. Low-d. lipoprotein was measured by the Lowry protein method. Ingesting 4-8 mL GJ/kg daily for 4 wk improved FMD of the brachial artery, without adverse effects on lipid and glucose metab. Both high and low doses of grape juice had similar effects on the endothelial function. Adding vitamin E to the diet with GJ did not further improve the endothelial function.
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    Dohadwala, M. M.; Hamburg, N. M.; Holbrook, M.; Kim, B. H.; Duess, M. A.; Levit, A.; Titas, M.; Chung, W. B.; Vincent, F. B.; Caiano, T. L.; Frame, A. A.; Keaney, J. F., Jr.; Vita, J. A. Effects of Concord grape juice on ambulatory blood pressure in prehypertension and stage 1 hypertension. Am. J. Clin. Nutr. 2010, 92 (5), 1052– 9,  DOI: 10.3945/ajcn.2010.29905
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    95
    Effects of Concord grape juice on ambulatory blood pressure in prehypertension and stage 1 hypertension
    Dohadwala, Mustali M.; Hamburg, Naomi M.; Holbrook, Monika; Kim, Brian H.; Duess, Mai-Ann; Levit, Aaron; Titas, Megan; Chung, William B.; Vincent, Felix B.; Caiano, Tara L.; Frame, Alissa A.; Keaney, John F., Jr.; Vita, Joseph A.
    American Journal of Clinical Nutrition (2010), 92 (5), 1052-1059CODEN: AJCNAC; ISSN:0002-9165. (American Society for Nutrition)
    Consumption of flavonoid-contg. foods may be useful for the management of hypertension. We investigated whether 100% Concord grape juice lowers blood pressure in patients with prehypertension and stage 1 hypertension. We conducted a double-blind crossover study to compare the effects of grape juice (7 mL/kg-1/d-1) and matched placebo beverage on 24-h ambulatory blood pressure, stress-induced changes in blood pressure, and biochem. profile. Participants consumed each beverage for 8 wk with a 4-wk rest period between beverages. They ceased consumption of grapes and other flavonoid-contg. beverages throughout the study. We enrolled 64 otherwise healthy patients taking no antihypertensive medications (31% women, 42% black, age 43 ± 12 y). Baseline mean (±SD) cuff blood pressure was 138 ± 7 (systolic)/82 ± 7 (diastolic) mm Hg. No effects on the primary endpoint of 24-h mean systolic blood pressure, diastolic blood pressure, or stress-induced changes in blood pressure were obsd. A secondary end-point was nocturnal dip in systolic pressure. At baseline, nocturnal pressure was 8.3 ± 7.1% lower at night than during daytime. The mean nocturnal dip increased 1.4 percentage points after grape juice and decreased 2.3 percentage points after placebo (P = 0.005). Fasting blood glucose was 91 ± 10 mg/dL at baseline for the entire cohort. Glucose decreased 2 mg/dL after consumption of grape juice and increased 1 mg/dL after consuming the placebo (P = 0.03). We obsd. no effect of grape juice on ambulatory blood pressure in this cohort of relatively healthy individuals with modestly elevated blood pressure. Secondary analyses suggested favorable effects on nocturnal dip and glucose homeostasis that may merit further investigation.
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    Kario, K.; Williams, B. Nocturnal Hypertension and Heart Failure: Mechanisms, Evidence, and New Treatments. Hypertension 2021, 78 (3), 564– 577,  DOI: 10.1161/HYPERTENSIONAHA.121.17440
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    Nocturnal Hypertension and Heart Failure: Mechanisms, Evidence, and New Treatments
    Kario, Kazuomi; Williams, Bryan
    Hypertension (2021), 78 (3), 564-577CODEN: HPRTDN; ISSN:0194-911X. (Lippincott Williams & Wilkins)
    A review. Heart failure (HF) is a common condition with an increasing prevalence. Despite a variety of evidence-based treatments for patients with HF with reduced ejection fraction, morbidity and mortality rates remain high. Furthermore, there are currently no treatments that have yet been shown to reduce complication and death rates in patients who have HF with preserved ejection fraction. Hypertension is a common comorbidity in patients with HF, contributing to disease development and prognosis. For example, hypertension is closely assocd. with the development of left ventricular hypertrophy, which an important precursor of HF. In particular, nighttime blood pressure (BP) appears to be an important, modifiable risk factor. Both nighttime BP and an abnormal circadian pattern of nighttime BP dipping have been shown to predict development of HF and the occurrence of cardiovascular events, independent of office BP. Key mechanisms for this assocn. include sodium handling/salt sensitivity and increased sympathetic activation. These pathogenic mechanisms are targeted by several new treatment options, including sodium-glucose cotransporter 2 inhibitors, angiotensin receptor neprilysin inhibitors, mineralocorticoid receptor antagonists, and renal denervation. All of these could form part of antihypertensive strategies designed to control nighttime BP and contribute to the goal of achieving perfect 24-h BP management. Nevertheless, addnl. research is needed to det. the effects of reducing nighttime BP and improving the circadian BP profile on the rate of HF, other cardiovascular events, and mortality.
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  97. 97
    Barona, J.; Aristizabal, J. C.; Blesso, C. N.; Volek, J. S.; Fernandez, M. L. Grape polyphenols reduce blood pressure and increase flow-mediated vasodilation in men with metabolic syndrome. J. Nutr. 2012, 142 (9), 1626– 32,  DOI: 10.3945/jn.112.162743
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    97
    Grape polyphenols reduce blood pressure and increase flow-mediated vasodilation in men with metabolic syndrome
    Barona, Jacqueline; Aristizabal, Juan C.; Blesso, Christopher N.; Volek, Jeff S.; Fernandez, Maria Luz
    Journal of Nutrition (2012), 142 (9), 1626-1632CODEN: JONUAI; ISSN:0022-3166. (American Society for Nutrition)
    We evaluated the effects of grape polyphenols in individuals classified with metabolic syndrome (MetS). Men (n = 24) aged 30-70 y were randomly assigned to consume either a freeze-dried grape polyphenol powder (GRAPE) or a placebo for 30 d in a double-blind, crossover design, sepd. by a 3-wk washout period. Participants were asked to maintain their usual diet and phys. activity during the study and abstain from consuming polyphenol-rich foods. MetS criteria including blood pressure (BP) and markers of vascular endothelial function including brachial artery flow-mediated vasodilation (FMD), plasma total nitrite + nitrate (NOx) to est. NO prodn., plasma sol. intercellular adhesion mol.-1 (sICAM-1), and sol. vascular cell adhesion mol.-1 (sVCAM-1) were measured at the end of each dietary period. Systolic BP (P < 0.0025) and plasma sICAM-1 concns. (P < 0.025) were lower, whereas the FMD response was higher (P < 0.0001), during the GRAPE compared with the placebo period. In addn., changes in sVCAM-1 concns. between periods were pos. correlated with changes in systolic BP (r = 0.45; P < 0.05). Although NOx concns. did not differ between periods, changes in systolic BP were neg. correlated with changes in NOx concns. (r = -0.44; P < 0.05), indicating the vasodilating properties of NO. Other MetS variables did not differ between the GRAPE and placebo periods. These results suggest that GRAPE polyphenols may potentiate vasorelaxation and reduce BP and circulating cell adhesion mols., resulting in improvements in vascular function.
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  98. 98
    Chaves, A. A.; Joshi, M. S.; Coyle, C. M.; Brady, J. E.; Dech, S. J.; Schanbacher, B. L.; Baliga, R.; Basuray, A.; Bauer, J. A. Vasoprotective endothelial effects of a standardized grape product in humans. Vascul Pharmacol 2009, 50 (1–2), 20– 6,  DOI: 10.1016/j.vph.2008.08.004
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    98
    Vasoprotective endothelial effects of a standardized grape product in humans
    Chaves, Alysia A.; Joshi, Mandar S.; Coyle, Christen M.; Brady, Joshua E.; Dech, Spencer J.; Schanbacher, Brandon L.; Baliga, Reshma; Basuray, Anupam; Bauer, John Anthony
    Vascular Pharmacology (2009), 50 (1-2), 20-26CODEN: VPAHAJ; ISSN:1537-1891. (Elsevier B.V.)
    The pathogenesis of coronary lesion development is a multi-factorial process involving a no. of different cell types and covariates, and injury and dysfunction of the vascular endothelium is an important marker and likely participant in the initiation and/or progression of most forms of heart disease. In addn. to chronic dysfunction of endothelial responses in patients with established heart disease, there is evidence that 'acute insults' can cause measurable dysfunction in vascular response in humans (drug toxicities, hypoxia, high fat meal). Such repeated acute insults may contribute to disease risk in otherwise healthy individuals or promote disease progression in established patients. Consumption of grape products, esp. wine, has been linked to lower cardiovascular risk but the vascular endothelial effects of grape products in healthy normal subjects, in the absence of ethanol, have not been evaluated. We therefore tested the hypotheses that (1) a standardized product derived from fresh grapes (GP, acute and chronic consumption) improves endothelial performance in healthy normal young subjects, and (2) that concomitant grape consumption affects the 'acute endothelial insult' caused by a single standardized high fat meal (HF). Acute consumption of GP equiv. to 1.25 cups of fresh grapes caused significant improvement in brachial artery flow mediated dilation (FMD) within 3 h of consumption, when compared to control consumption of sugar soln. (p < 0.05). No acute changes in heart rate, hemodynamics, or lipid profiles were obsd. When this 'dose' was then consumed twice daily for 3 wk FMD was further improved and total antioxidant capacity in plasma was slightly increased (p < 0.05), with no change in heart rate, hemodynamics, or lipid profiles. A single HF meal (900 cal, 49 g total fat) caused a 50% redn. in FMD response when consumed alone, and this effect coincided with increased blood triglyceride levels within 3 h post-consumption. In contrast the concomitant consumption of GP with the HF meal completely prevented this HF-induced vascular endothelial dysfunction (p < 0.05), but had no effect on rising triglycerides. These data demonstrate that a modest intake of fresh grapes can have acute favorable effects on vascular endothelial function in normal healthy subjects, that chronic intake can further improve performance and concomitant intake can blunt the 'acute insult' to endothelium caused by a typical western HF meal. This effect is likely to be related to antioxidant effects at the endothelium, rather than changes in blood lipids. These data support epidemiol. data of the health benefits of grapes, and demonstrate that 'favorable' food consumption can apparently reduce some toxicities induced by 'unfavorable' food consumption.
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  99. 99
    Bardagjy, A. S.; Hu, Q.; Giebler, K. A.; Ford, A.; Steinberg, F. M. Effects of grape consumption on biomarkers of inflammation, endothelial function, and PBMC gene expression in obese subjects. Arch. Biochem. Biophys. 2018, 646, 145– 152,  DOI: 10.1016/j.abb.2018.04.003
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    99
    Effects of grape consumption on biomarkers of inflammation, endothelial function, and PBMC gene expression in obese subjects
    Bardagjy, Allison S.; Hu, Qian; Giebler, Kathryn A.; Ford, Addison; Steinberg, Francene M.
    Archives of Biochemistry and Biophysics (2018), 646 (), 145-152CODEN: ABBIA4; ISSN:0003-9861. (Elsevier B.V.)
    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 resp. treatment daily for 4 wk to det. 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 3h (p<0.05) and decreased plasma endothelin-1 (ET-1) concn. at 5h (p<0.05) after meal challenge compared with PBO. Following 4 wk of daily GP consumption, sol. vascular cell adhesion mol. 1 (sVCAM-1) plasma concn. increased compared with PBO (p<0.05), however baseline values differed between treatments. In conclusion, GP consumption resulted in decreased vasoconstrictor ET-1 concn. and increased gene expression related to oxidative stress defense following HFHC meal. Except for increase in sVCAM-1 concn., 4 wk 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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  100. 100
    Kokkou, E.; Siasos, G.; Georgiopoulos, G.; Oikonomou, E.; Verveniotis, A.; Vavuranakis, M.; Zisimos, K.; Plastiras, A.; Kollia, M. E.; Stefanadis, C.; Papavassiliou, A. G.; Tousoulis, D. The impact of dietary flavonoid supplementation on smoking-induced inflammatory process and fibrinolytic impairment. Atherosclerosis 2016, 251, 266– 272,  DOI: 10.1016/j.atherosclerosis.2016.06.054
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    100
    The impact of dietary flavonoid supplementation on smoking-induced inflammatory process and fibrinolytic impairment
    Kokkou, Eleni; Siasos, Gerasimos; Georgiopoulos, Georgios; Oikonomou, Evangelos; Verveniotis, Aleksis; Vavuranakis, Manolis; Zisimos, Konstantinos; Plastiras, Aris; Kollia, Maria-Eleni; Stefanadis, Christodoulos; Papavassiliou, Athanasios G.; Tousoulis, Dimitris
    Atherosclerosis (Amsterdam, Netherlands) (2016), 251 (), 266-272CODEN: ATHSBL; ISSN:0021-9150. (Elsevier B.V.)
    Smoking is assocd. with increased inflammatory process and impairment of fibrinolytic status. Concord grape juice (CGJ), a rich source of flavonoids, can modify cardiovascular risk factors. We aimed to evaluate the impact of CGJ on smoking-induced impairment of inflammatory and fibrinolytic status in healthy smokers. We studied the effect of a 2-wk oral treatment with CGJ in 26 healthy smokers on three occasions (day 0: baseline, day 7 and day 14) in a randomized, placebo-controlled, double-blind, cross-over design. Measurements were carried out before (pSm) and 20 min after (Sm20) cigarette smoking. Serum levels of intercellular adhesion mol.-1 (sICAM-1) and plasminogen activator inhibitor 1 (PAI-1) were measured as markers of inflammatory and fibrinolytic status, resp. Treatment with CGJ reduced pSm sICAM-1 levels (p < 0.001), while placebo had no impact on ICAM-1 levels (p = 0.31). Moreover, treatment with CGJ decreased pSm values of PAI-1 (p < 0.001) while placebo had no impact on PAI-1 levels (p = 0.89). Smoking induced an elevation in PAI-1 levels after smoking compared to pro-smoking levels in all study days and in both arms (CGJ and placebo) of the study (p < 0.001 for all). Interestingly, CGJ compared to placebo, attenuated the acute smoking increase in sICAM-1 and PAI-1 levels (p < 0.001 and p = 0.005 resp.). CGJ consumption improved inflammatory and fibrinolytic status in healthy smokers and attenuated acute smoking induced increase in ICAM-1 and PAI-1 levels. These findings shed further light on the favorable effects of flavonoids in cardiovascular health.
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  101. 101
    Castilla, P.; Davalos, A.; Teruel, J. L.; Cerrato, F.; Fernandez-Lucas, M.; Merino, J. L.; Sanchez-Martin, C. C.; Ortuno, J.; Lasuncion, M. A. Comparative effects of dietary supplementation with red grape juice and vitamin E on production of superoxide by circulating neutrophil NADPH oxidase in hemodialysis patients. Am. J. Clin. Nutr. 2008, 87 (4), 1053– 61,  DOI: 10.1093/ajcn/87.4.1053
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    101
    Comparative effects of dietary supplementation with red grape juice and vitamin E on production of superoxide by circulating neutrophil NADPH oxidase in hemodialysis patients
    Castilla, Patricia; Davalos, Alberto; Teruel, Jose Luis; Cerrato, Francisca; Fernandez-Lucas, Milagros; Merino, Jose Luis; Sanchez-Martin, Carolina C.; Ortuno, Joaquin; Lasuncion, Miguel A.
    American Journal of Clinical Nutrition (2008), 87 (4), 1053-1061CODEN: AJCNAC; ISSN:0002-9165. (American Society for Nutrition)
    Background: Atherosclerotic cardiovascular disease is the most common cause of death among hemodialysis patients; it has been attributed to increased oxidative stress, dyslipidemia, malnutrition, and chronic inflammation. Activation of neutrophils is a well-recognized feature in dialysis patients, and superoxide-anion prodn. by neutrophil NADPH oxidase may contribute significantly to oxidative stress. Objective: The aim of the study was to compare the effects of dietary supplementation with concd. red grape juice (RGJ), a source of polyphenols, and vitamin E on neutrophil NADPH oxidase activity and other cardiovascular risk factors in hemodialysis patients. Design: Thirty-two patients undergoing hemodialysis were recruited and randomly assigned to groups to receive dietary supplementation with RGJ, vitamin E, or both or a control condition without supplementation or placebo. Blood was obtained at baseline and on days 7 and 14 of treatment. Results: RGJ consumption but not vitamin E consumption reduced plasma concns. of total cholesterol and apolipoprotein B and increased those of HDL cholesterol. Both RGJ and vitamin E reduced plasma concns. of oxidized LDL and ex vivo neutrophil NADPH oxidase activity. These effects were intensified when the supplements were used in combination; in that case, redns. in the inflammatory biomarkers intercellular adhesion mol. 1 and monocyte chemoattractant protein 1 also were obsd. Conclusions: Regular ingestion of concd. RGJ by hemodialysis patients reduces neutrophil NADPH-oxidase activity and plasma concns. of oxidized LDL and inflammatory biomarkers to a greater extent than does that of vitamin E. This effect of RGJ consumption may favor a redn. in cardiovascular risk.
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  102. 102
    Castilla, P.; Echarri, R.; Davalos, A.; Cerrato, F.; Ortega, H.; Teruel, J. L.; Lucas, M. F.; Gomez-Coronado, D.; Ortuno, J.; Lasuncion, M. A. Concentrated red grape juice exerts antioxidant, hypolipidemic, and antiinflammatory effects in both hemodialysis patients and healthy subjects. Am. J. Clin. Nutr. 2006, 84 (1), 252– 62,  DOI: 10.1093/ajcn/84.1.252
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    102
    Concentrated red grape juice exerts antioxidant, hypolipidemic, and antiinflammatory effects in both hemodialysis patients and healthy subjects
    Castilla, Patricia; Echarri, Rocio; Davalos, Alberto; Cerrato, Francisca; Ortega, Henar; Teruel, Jose Luis; Lucas, Milagros Fernandez; Gomez-Coronado, Diego; Ortuno, Joaquin; Lasuncion, Miguel A.
    American Journal of Clinical Nutrition (2006), 84 (1), 252-262CODEN: AJCNAC; ISSN:0002-9165. (American Society for Nutrition)
    Background: Patients treated with hemodialysis frequently experience cardiovascular complications attributed, among other causes, to dyslipidemia, increased oxidative stress, and inflammation. Objective: The aim of the study was to study the effects of dietary supplementation with concd. red grape juice (RGJ), a source of polyphenols, on lipoprotein profile, antioxidant capacity, LDL oxidn., and inflammatory biomarkers. Design: Twenty-six patients receiving hemodialysis and 15 healthy subjects were instructed to drink 100 mL RGJ/d for 14 d. Blood was drawn at baseline, twice during RGJ supplementation, and twice during the 6-mo follow-up period. As a control, 12 other randomly recruited hemodialysis patients not receiving RGJ were studied. Lipids, apolipoproteins, oxidized LDL, and antioxidant vitamins were measured in plasma. The bioavailability of RGJ polyphenols was assessed in healthy subjects. Results: The max. plasma concn. of quercetin was achieved 3 h after RGJ ingestion, which indicates that supplement-derived polyphenols are rapidly absorbed. In both healthy subjects and hemodialysis patients, RGJ consumption increased the antioxidant capacity of plasma without affecting concns. of uric acid or ascorbic acid; reduced the concn. of oxidized LDL; and increased the concn. of cholesterol-standardized α-tocopherol. RGJ supplementation also caused a significant decrease in LDL-cholesterol and apolipoprotein B-100 concns., while increasing the concns. of HDL cholesterol and apolipoprotein A-I. In a further study in hemodialysis patients, RGJ supplementation for 3 wk significantly reduced plasma monocyte chemoattractant protein 1, an inflammatory biomarker assocd. with cardiovascular disease risk. Conclusion: Dietary supplementation with concd. RGJ improves the lipoprotein profile, reduces plasma concns. of inflammatory biomarkers and oxidized LDL, and may favor a redn. in cardiovascular disease risk.
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  103. 103
    Ammollo, C. T.; Semeraro, F.; Milella, R. A.; Antonacci, D.; Semeraro, N.; Colucci, M. Grape intake reduces thrombin generation and enhances plasma fibrinolysis. Potential role of circulating procoagulant microparticles. J. Nutr Biochem 2017, 50, 66– 73,  DOI: 10.1016/j.jnutbio.2017.08.012
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    103
    Grape intake reduces thrombin generation and enhances plasma fibrinolysis. Potential role of circulating procoagulant microparticles
    Ammollo, Concetta T.; Semeraro, Fabrizio; Milella, Rosa Anna; Antonacci, Donato; Semeraro, Nicola; Colucci, Mario
    Journal of Nutritional Biochemistry (2017), 50 (), 66-73CODEN: JNBIEL; ISSN:0955-2863. (Elsevier)
    Phytochems. contained in grapes down-regulate several prothrombotic pathways in vitro. We evaluated the effect of grape consumption on coagulation and fibrinolysis in healthy volunteers. Thirty subjects were enrolled: 20 were given grape (5 g/kg body wt./day for 3 wk), while 10 served as controls. Blood samples were taken at baseline (T0), at the end of the grape diet (T1) and after 4-wk wash-out (T2). Grape intake caused a significant decrease of the procoagulant and inflammatory responses of whole blood and/or mononuclear cells to bacterial lipopolysaccharide at both T1 and T2. At plasma level, grape diet decreased thrombin generation at T1 and T2, largely through a redn. in the no. and/or activity of procoagulant microparticles. This anticoagulant effect resulted in the formation of clots that were more susceptible to fibrinolysis, mainly because of a lesser activation of thrombin activatable fibrinolysis inhibitor. No difference in any variables was detected in controls at the time points considered. In conclusion, chronic grape consumption induces sustained anticoagulant and profibrinolytic effects with potential benefits for human health.
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  104. 104
    Yang, J.; Kurnia, P.; Henning, S. M.; Lee, R.; Huang, J.; Garcia, M. C.; Surampudi, V.; Heber, D.; Li, Z. Effect of Standardized Grape Powder Consumption on the Gut Microbiome of Healthy Subjects: A Pilot Study. Nutrients 2021, 13 (11), 3965,  DOI: 10.3390/nu13113965
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    104
    Effect of Standardized Grape Powder Consumption on the Gut Microbiome of Healthy Subjects: A Pilot Study
    Yang, Jieping; Kurnia, Patrick; Henning, Susanne M.; Lee, Rupo; Huang, Jianjun; Garcia, Michael C.; Surampudi, Vijaya; Heber, David; Li, Zhaoping
    Nutrients (2021), 13 (11), 3965CODEN: NUTRHU; ISSN:2072-6643. (MDPI AG)
    Grapes provide a rich source of polyphenols and fibers. This study aimed to evaluate the effect of the daily consumption of 46 g of whole grape powder, providing the equiv. of two servings of California table grapes, on the gut microbiome and cholesterol/bile acid metab. in healthy adults. This study included a 4-wk standardization to a low-polyphenol diet, followed by 4 wk of 46 g of grape powder consumption while continuing the low-polyphenol diet. Compared to the baseline, 4 wk of grape powder consumption significantly increased the alpha diversity index of the gut microbiome. There was a trend of increasing Verrucomicrobia (p = 0.052) at the phylum level, and a significant increase in Akkermansia was noted. In addn., there was an increase in Flavonifractor and Lachnospiraceae_UCG-010, but a decrease in Bifidobacterium and Dialister at the genus level. Grape powder consumption significantly decreased the total cholesterol by 6.1% and HDL cholesterol by 7.6%. There was also a trend of decreasing LDL cholesterol by 5.9%, and decreasing total bile acid by 40.9%. Blood triglyceride levels and body compn. were not changed by grape powder consumption. In conclusion, grape powder consumption significantly modified the gut microbiome and cholesterol/bile acid metab.
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  105. 105
    Zern, T. L.; Wood, R. J.; Greene, C.; West, K. L.; Liu, Y.; Aggarwal, D.; Shachter, N. S.; Fernandez, M. L. Grape polyphenols exert a cardioprotective effect in pre- and postmenopausal women by lowering plasma lipids and reducing oxidative stress. J. Nutr. 2005, 135 (8), 1911– 7,  DOI: 10.1093/jn/135.8.1911
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    105
    Grape polyphenols exert a cardioprotective effect in pre- and postmenopausal women by lowering plasma lipids and reducing oxidative stress
    Zern, Tosca L.; Wood, Richard J.; Greene, Christine; West, Kristy L.; Liu, Yanzhu; Aggarwal, Dimple; Shachter, Neil S.; Fernandez, Maria Luz
    Journal of Nutrition (2005), 135 (8), 1911-1917CODEN: JONUAI; ISSN:0022-3166. (American Society for Nutritional Sciences)
    To evaluate the effects of grape polyphenols on plasma lipids, inflammatory cytokines, and oxidative stress, 24 pre- and 20 postmenopausal women were randomly assigned to consume 36 g of a lyophilized grape powder (LGP) or a placebo for 4 wk. The LGP consisted of 92% carbohydrate and was rich in flavans, anthocyanins, quercetin, myricetin, kaempferol, and resveratrol. After a 3-wk washout period, subjects were assigned to the alternate treatment for an addnl. 4 wk. The placebo consisted of an equal ratio of fructose and dextrose and was similar in appearance and energy content (554 kJ) to LGP. Plasma triglyceride concns. were reduced by 15 and 6% in pre- and postmenopausal women, resp. (P < 0.01) after LGP supplementation. In addn., plasma LDL cholesterol and apolipoproteins B and E were lower due to LGP treatment (P < 0.05). Further, cholesterol ester transfer protein activity was decreased by ∼15% with intake of LGP (P < 0.05). In contrast to these beneficial effects on plasma lipids, LDL oxidn. was not modified by LGP treatment. However, whole-body oxidative stress as measured by urinary F2-isoprostanes was significantly reduced after LGP supplementation. LGP also decreased the levels of plasma tumor necrosis factor-α, which plays a major role in the inflammation process. Through alterations in lipoprotein metab., oxidative stress, and inflammatory markers, LGP intake beneficially affected key risk factors for coronary heart disease in both pre- and postmenopausal women.
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  106. 106
    Corredor, Z.; Rodriguez-Ribera, L.; Coll, E.; Montanes, R.; Diaz, J. M.; Ballarin, J.; Marcos, R.; Pastor, S. Unfermented grape juice reduce genomic damage on patients undergoing hemodialysis. Food Chem. Toxicol. 2016, 92, 1– 7,  DOI: 10.1016/j.fct.2016.03.016
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    106
    Unfermented grape juice reduce genomic damage on patients undergoing hemodialysis
    Corredor, Zuray; Rodriguez-Ribera, Lara; Coll, Elisabeth; Montanes, Rosario; Diaz, Juan Manuel; Ballarin, Jose; Marcos, Ricard; Pastor, Susana
    Food and Chemical Toxicology (2016), 92 (), 1-7CODEN: FCTOD7; ISSN:0278-6915. (Elsevier Ltd.)
    Chronic kidney disease (CKD) patients in dialysis (HD) are considered to be submitted to a continuous oxidative stress. This stress can cause damage on DNA and, consequently, contribute to the high levels of DNA damage obsd. in these patients. Due to the well-known role of polyphenols as antioxidant agents we proposed its use to reduce the levels of genotoxicity present in HD-CKD patients. The objective of this study was to evaluate the antigenotoxic effects of unfermented grape juice (UGJ) on HD-CKD patients. The levels of DNA damage were analyzed using different biomarkers, such as breaks and oxidized DNA bases by the comet assay, chromosome damage by the micronucleus test. In addn., TEAC (Trolox equiv. antioxidant capacity) was also evaluated. Thirty-nine patients were followed for six months, of whom 25 were supplemented by UGJ and 14 were not supplemented. The obtained results showed a significant decrease in the underlying levels of oxidative DNA damage, in the supplemented group. Regarding the clin. parameters, LDL and cholesterol, were significantly reduced in the patients studied after the supplementation period, although cholesterol was also decreased in the non-supplemented patients. In conclusion, in our studied group the supplementation with UGJ reduced the levels of oxidative DNA damage of HD-CKD patients.
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  107. 107
    Toscano, L. T.; Silva, A. S.; Toscano, L. T.; Tavares, R. L.; Biasoto, A. C. T.; de Camargo, A. C.; da Silva, C. S. O.; Gonçalves, M. d. C. R.; Shahidi, F. Phenolics from purple grape juice increase serum antioxidant status and improve lipid profile and blood pressure in healthy adults under intense physical training. Journal of Functional Foods 2017, 33, 419– 424,  DOI: 10.1016/j.jff.2017.03.063
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    107
    Phenolics from purple grape juice increase serum antioxidant status and improve lipid profile and blood pressure in healthy adults under intense physical training
    Toscano, Lydiane Tavares; Silva, Alexandre Sergio; Toscano, Luciana Tavares; Tavares, Renata Leite; Biasoto, Aline Camarao Telles; Costa de Camargo, Adriano; Oliveira da Silva, Cassia Surama; Goncalves, Maria da Conceicao Rodrigues; Shahidi, Fereidoon
    Journal of Functional Foods (2017), 33 (), 419-424CODEN: JFFOAX; ISSN:1756-4646. (Elsevier Ltd.)
    Phenolic compds. have generated considerable interest in the scientific community and the media. Much of this interest is due to the properties ascribed to several phenolic compds. for prevention of cancer, dyslipidemia, and obesity. Grape juice made from cultivars Isabel, Bordeaux and Concord, was characterized in this work. Subsequently, twenty-eight healthy adults were randomly assigned to a group that consumed grape juice (GJG = 15; 25-54 years old) and a group that consumed a control beverage (CG = 13; 20-53 years old). The groups were evaluated for their nutritional status, blood pressure, and blood collection for anal. of total antioxidant capacity, nitrite, glucose and lipid profile, upon receiving supplementation (10 m/kg/day) for 28 days and reevaluated at the end. The results suggest that purple grape juice had a great potential as an antioxidant source in improving antioxidant status and cardiometabolic profile of healthy adults under intense phys. exercise.
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  108. 108
    Rahbar, A. R.; Mahmoudabadi, M. M.; Islam, M. S. Comparative effects of red and white grapes on oxidative markers and lipidemic parameters in adult hypercholesterolemic humans. Food Funct 2015, 6 (6), 1992– 8,  DOI: 10.1039/C5FO00100E
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    108
    Comparative effects of red and white grapes on oxidative markers and lipidemic parameters in adult hypercholesterolemic humans
    Rahbar, Ali Reza; Mahmoudabadi, Mohammad Mehdi Shakouri; Islam, Md. Shahidul
    Food & Function (2015), 6 (6), 1992-1998CODEN: FFOUAI; ISSN:2042-6496. (Royal Society of Chemistry)
    The present study compared the effects of consuming red vs. white whole grapes on oxidative and lipidemic indexes in people with hypercholesterolemia. Sixty nine patients were randomized into three groups. The two treatment groups consumed 500 g of either Condori red grapes or Shahroodi white grapes daily for 8 wk, and the third group served as a control. Plasma glucose, triacylglycerol (TG), cholesterol, low-d. lipoprotein cholesterol (LDL-C), high-d. lipoprotein cholesterol (HDL-C), thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity (TAC) were detd. by colorimetric methods at baseline and at the end of the study. In addn., the polyphenol and fiber content of the two grape varieties was measured. TBARS was reduced in both study groups compared to the control group, and the redn. was greater in the group that consumed red grapes compared to the white grapes. TAC was increased significantly in both red and white grape consuming groups compared to the control group. Total cholesterol and LDL-C were decreased in the red grape group compared to the control group. No significant changes in fasting blood glucose, TG or HDL-C were obsd. among the groups. The results of this study suggest that consumption of the whole fruit of red grapes has more potent anti-oxidative and hypolipidemic effects compared to the white grapes in hyperlipidemic adult humans. Hence, the whole fruit of red grapes may be an excellent fruit choice not only to prevent oxidative stress related metabolic disorders but also cholesterol related cardiovascular diseases, particularly in hyperlipidemic adult humans.
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  109. 109
    Lupoli, R.; Ciciola, P.; Costabile, G.; Giacco, R.; Di Minno, M. N. D.; Capaldo, B. Impact of Grape Products on Lipid Profile: A Meta-Analysis of Randomized Controlled Studies. J. Clin Med. 2020, 9 (2), 313,  DOI: 10.3390/jcm9020313
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    109
    Impact of grape products on lipid profile: a meta-analysis of randomized controlled studies
    Lupoli, Roberta; Ciciola, Paola; Costabile, Giuseppina; Giacco, Rosalba; Di Minno, Matteo Nicola Dario; Capaldo, Brunella
    Journal of Clinical Medicine (2020), 9 (2), 313CODEN: JCMOHK; ISSN:2077-0383. (MDPI AG)
    Background: Growing evidence shows that grape polyphenols can improve cardiovascular risk factors. Although there are clear data supporting a beneficial effect of grape supplementation on blood pressure and glucose metab., the effects of grape polyphenols on lipid metab. are still controversial. Objective: We performed a meta-anal. of randomized controlled trials (RCTs) to assess the effect of grape products on lipid profile. Design: A systematic search was performed in the PubMed, Web of Science, Scopus, and EMBASE databases without any language or publication year restriction. The ref. lists of all retrieved articles were manually reviewed. RCTs evaluating the impact of grape products/juice/exts. on lipid profile were included. Difference in total cholesterol (TC), high-d. lipoprotein cholesterol (HDL-C), low-d. lipoprotein cholesterol (LDL-C), triglycerides (TG), oxidized low-d. lipoprotein cholesterol (oxLDL-C), apolipoprotein (apo) A, apo B before and after administration of grape products or placebo were expressed as mean differences (MD) with pertinent 95% confidence intervals (95% CI). The impact of clin. and demog. features on effect size was assessed by meta-regression. Results: The administration of grape products is assocd. with a significant improvement of lipid profile, as evidenced by changes in TC (MD: -7.6 mg/dL (-0.2 mmol/L); 95% CI: -10.8, -4.4; p < 0.001), HDL-C (MD: 1.4 mg/dL (0.04 mmol/L); 95% CI: 0.8, 1.9; p < 0.001, I2 = 74.7%, p < 0.001), LDL-C (-6.3 mg/dL (-0.16 mmol/L); 95% CI: -9.5, -3.0; p < 0.001), oxLDL-C (MD: -4.5 U/L; 95% CI: -7.5, -1.5; p = 0.003, I2 = 90.6%, p < 0.001), apo B (MD: -2.4 mg/dL (-0.05 μmol/L); 95% CI: -4.5, -0.3; p = 0.026), and TG (MD: -14.5 mg/dL (-0.16 mmol/L); 95% CI: -17.7, -11.2; p < 0.001) levels in subjects receiving grape products compared to placebo. With regard to the extent of the lipid-lowering effect, compared to baseline values, the highest redn. was reported for LDL-C (MD: -5.6 mg/dL (-0.14 mmol/L); 95% CI: -9.5, -1.7; p = 0.005) and for oxLDL-C (MD: -5.0 U/L; 95% CI: -8.8, -1.2; p = 0.010, I2 = 0%, p = 0.470). Conclusions: Grape polyphenols exert a favorable effect on lipid profile in humans by significantly reducing plasma levels of LDL-C and oxLDL-C.
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  110. 110
    Rodriguez-Mateos, A.; Istas, G.; Boschek, L.; Feliciano, R. P.; Mills, C. E.; Boby, C.; Gomez-Alonso, S.; Milenkovic, D.; Heiss, C. Circulating Anthocyanin Metabolites Mediate Vascular Benefits of Blueberries: Insights From Randomized Controlled Trials, Metabolomics, and Nutrigenomics. J. Gerontol A Biol. Sci. Med. Sci. 2019, 74 (7), 967– 976,  DOI: 10.1093/gerona/glz047
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    110
    Circulating Anthocyanin Metabolites Mediate Vascular Benefits of Blueberries: Insights From Randomized Controlled Trials, Metabolomics, and Nutrigenomics
    Rodriguez-Mateos Ana; Istas Geoffrey; Mills Charlotte E; Rodriguez-Mateos Ana; Istas Geoffrey; Boschek Lisa; Feliciano Rodrigo P; Heiss Christian; Mills Charlotte E; Boby Celine; Milenkovic Dragan; Gomez-Alonso Sergio; Milenkovic Dragan; Heiss Christian; Heiss Christian
    The journals of gerontology. Series A, Biological sciences and medical sciences (2019), 74 (7), 967-976 ISSN:.
    Potential health benefits of blueberries may be due to vascular effects of anthocyanins that predominantly circulate in blood as phenolic acid metabolites. We investigated which role blueberry anthocyanins and circulating metabolites play in mediating improvements in vascular function and explore potential mechanisms using metabolomics and nutrigenomics. Purified anthocyanins exerted a dose-dependent improvement of endothelial function in healthy humans, as measured by flow-mediated dilation. The effects were similar to those of wild blueberries containing similar amounts of anthocyanins, whereas control drinks containing fiber, minerals, or vitamins had no significant effect. Daily 1-month wild blueberry consumption increased flow-mediated dilation and lowered 24-hour ambulatory systolic blood pressure. Of the 63 anthocyanin plasma metabolites quantified, 14 and 21 correlated with acute and chronic flow-mediated dilation improvements, respectively. Injection of these metabolites improved flow-mediated dilation in mice. Daily wild blueberry consumption led to differential expression (>1.2-fold) of 608 genes and 3 microRNAs, with Mir-181c showing a 13-fold increase in peripheral blood mononuclear cells. Patterns of 13 metabolites were independent predictors of gene expression changes and pathway enrichment analysis revealed significantly modulated biological processes involved in cell adhesion, migration, immune response, and cell differentiation. Our results identify anthocyanin metabolites as major mediators of vascular bioactivities of blueberries and changes of cellular gene programs. Trial registration: NCT025208.
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  111. 111
    Rodriguez-Mateos, A.; Rendeiro, C.; Bergillos-Meca, T.; Tabatabaee, S.; George, T. W.; Heiss, C.; Spencer, J. P. Intake and time dependence of blueberry flavonoid-induced improvements in vascular function: a randomized, controlled, double-blind, crossover intervention study with mechanistic insights into biological activity. Am. J. Clin. Nutr. 2013, 98 (5), 1179– 91,  DOI: 10.3945/ajcn.113.066639
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    111
    Intake and time dependence of blueberry flavonoid-induced improvements in vascular function: a randomized, controlled, double-blind, crossover intervention study with mechanistic insights into biological activity
    Rodriguez-Mateos, Ana; Rendeiro, Catarina; Bergillos-Meca, Triana; Tabatabaee, Setareh; George, Trevor W.; Heiss, Christian; Spencer, Jeremy P. E.
    American Journal of Clinical Nutrition (2013), 98 (5), 1179-1191CODEN: AJCNAC; ISSN:0002-9165. (American Society for Nutrition)
    Background: There are very limited data regarding the effects of blueberry flavonoid intake on vascular function in healthy humans. Objectives: We investigated the impact of blueberry flavonoid intake on endothelial function in healthy men and assessed potential mechanisms of action by the assessment of circulating metabolites and neutrophil NADPH oxidase activity. Design: Two randomized, controlled, double-blind, crossover human-intervention trials were conducted with 21 healthy men. Initially, the impact of blueberry flavonoid intake on flow-mediated dilation (FMD) and polyphenol absorption and metab. was assessed at baseline and 1, 2, 4, and 6 h after consumption of blueberry contg. 766, 1278, and 1791 mg total blueberry polyphenols or a macronutrient- and micronutrient-matched control drink (0 mg total blueberry polyphenols). Second, an intake-dependence study was conducted (from baseline to 1 h) with 319, 637, 766, 1278, and 1791 mg total blueberry polyphenols and a control. Results: We obsd. a biphasic time-dependent increase in FMD, with significant increases at 1-2 and 6 h after consumption of blueberry polyphenols. No significant intake-dependence was obsd. between 766 and 1791 mg. However, at 1 h after consumption, FMD increased dose dependently to ≤766 mg total blueberry polyphenol intake, after which FMD plateaued. Increases in FMD were closely linked to increases in circulating metabolites and by decreases in neutrophil NADPH oxidase activity at 1-2 and 6 h. Conclusions: Blueberry intake acutely improves vascular function in healthy men in a time- and intake-dependent manner. These benefits may be mechanistically linked to the actions of circulating phenolic metabolites on neutrophil NADPH oxidase activity.
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  112. 112
    Corban, M. T.; Widmer, R. J.; Cilluffo, R.; Kazeck, M. A.; Lennon, R. J.; Lerman, L. O.; Lerman, A. The effect of polyphenol-rich chardonnay seed supplements on peripheral endothelial function. Eur. J. Nutr 2020, 59 (8), 3723– 3734,  DOI: 10.1007/s00394-020-02203-6
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    112
    The effect of polyphenol-rich chardonnay seed supplements on peripheral endothelial function
    Corban, Michel T.; Widmer, Robert Jay; Cilluffo, Rebecca; Kazeck, Makinzee A.; Lennon, Ryan J.; Lerman, Lilach O.; Lerman, Amir
    European Journal of Nutrition (2020), 59 (8), 3723-3734CODEN: EJNUFZ; ISSN:1436-6207. (Springer)
    Objective: Peripheral endothelial dysfunction (PED) is assocd. with major adverse cardiovascular events. Similar to cardio-protective Mediterranean diet, Chardonnay seeds are rich in polyphenols, fibers, and grape seed oil. In this randomized double-blinded trial, we investigated safety and incremental benefit of Chardonnay seed polyphenols-rich (PR), compared to polyphenols-free (PF), supplements on PED. Methods: 89 patients with PED [reactive hyperemia-peripheral arterial tonometry (RH-PAT) index ≤ 2 ] were randomized 1:1 to 4.8 g (6 capsules)/day PR or PF for 4 mo. PR and PF capsules had equal amts. of seed oil (∼ 7% capsule wt.), fibers, and carbohydrates, but only PR capsules contained polyphenols (∼ 11% capsule wt.). Baseline and follow-up RH-PAT indexes (primary endpoint) and endothelial progenitor cells (EPC) levels were measured. Patients were asked to maintain their regular diet and exercise habits during study period. Results: Baseline RH-PAT indexes, demographics, lab values, and EPC levels were similar between groups. No significant adverse reactions to PR or PF were reported. Follow-up RH-PAT indexes significantly increased (p < 0.05 vs. baseline) in both groups to similar extent (31 ± 39% PR vs. 49 ± 53% PF, p = 0.09). Circulating CD34 + EPCs equally increased (median + 55% vs. + 54%, p = 0.94) in PR and PF groups, resp. Conclusion: PR and PF Chardonnay seed supplements were safe and improved peripheral endothelial function to similar extent in PED patients. However, there were no incremental benefits of PR over PF on RH-PAT indexes or CD34 + EPC levels. Chardonnay seed supplements role in primary prevention of atherosclerosis, as add-on to healthy lifestyle and guidelines directed medical therapy, should be further explored.
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  113. 113
    Martin, M. E.; Grao-Cruces, E.; Millan-Linares, M. C.; Montserrat-de la Paz, S. Grape (Vitis vinifera L.) Seed Oil: A Functional Food from the Winemaking Industry. Foods 2020, 9 (10), 1360,  DOI: 10.3390/foods9101360
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    113
    Grape (Vitis vinifera L.) seed oil: a functional food from the winemaking industry
    Martin, Maria E.; Grao-Cruces, Elena; Millan-Linares, Maria C.; Montserrat-de la Paz, Sergio
    Foods (2020), 9 (10), 1360CODEN: FOODBV; ISSN:2304-8158. (MDPI AG)
    Wine prodn. is an ancient human activity that generates several byproducts, which include some constituents known for their potential in health care and for their role in the food or cosmetic industries. Any variety of grape (Vitis vinifera L.) contains nutrients and bioactive compds. available from their juice or solid parts. Grape seed ext. has demonstrated many activities in disease prevention, such as antioxidant effects, which make it a potential source of nutraceuticals. Grape seed is a remarkable winery industry byproduct due to the bioactivity of its constituents. Methods for recovery of oil from grape seeds have evolved to improve both the quantity and quality of the yield. Both the lipophilic and hydrophilic chems. present in the oil of V. vinifera L. make this wine byproduct a source of natural nutraceuticals. Food and non-food industries are becoming novel targets of oil obtained from grape seeds given its various properties. This review focuses on the advantages of grape seed oil intake in our diet regarding its chem. compn. in industries not related to wine prodn. and the economic and environmental impact of oil prodn.
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  114. 114
    Kim, H.; Bartley, G. E.; Arvik, T.; Lipson, R.; Nah, S.-Y.; Seo, K.; Yokoyama, W. Dietary Supplementation of Chardonnay Grape Seed Flour Reduces Plasma Cholesterol Concentration, Hepatic Steatosis, and Abdominal Fat Content in High-Fat Diet-Induced Obese Hamsters. J. Agric. Food Chem. 2014, 62 (8), 1919– 1925,  DOI: 10.1021/jf404832s
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    114
    Dietary Supplementation of Chardonnay Grape Seed Flour Reduces Plasma Cholesterol Concentration, Hepatic Steatosis, and Abdominal Fat Content in High-Fat Diet-Induced Obese Hamsters
    Kim, Hyunsook; Bartley, Glenn E.; Arvik, Torey; Lipson, Rebecca; Nah, Seung-Yeol; Seo, Kunho; Yokoyama, Wallace
    Journal of Agricultural and Food Chemistry (2014), 62 (8), 1919-1925CODEN: JAFCAU; ISSN:0021-8561. (American Chemical Society)
    The mechanisms for the hypocholesterolemic and antiobesity effects of grape seed flours derived from white and red winemaking processing were investigated using male Golden Syrian hamsters fed high-fat (HF) diets supplemented with 10% partially defatted grape seed flours from Chardonnay (ChrSd), Cabernet Sauvignon (CabSd), or Syrah (SyrSd) pomace as compared to a HF control diet for 3 wk. Hamsters fed the ChrSd diet had significantly lowered plasma total-, VLDL-, and LDL-cholesterol concns. compared to the CabSd, SyrSd, and control diets. The improved plasma cholesterol after ChrSd was correlated with the up-regulation of hepatic genes related to cholesterol (CYP51) and bile acid (CYP7A1) synthesis as well as LDL-cholesterol uptake (LDLR). A redn. of hepatic lipid content was assocd. with altered expression of the genes related to lipid metab. However, fecal total lipid content was not changed. Expression of ileal apical sodium bile acid transporter (ASBT) was not affected by ChrSd, indicating unchanged ileal bile acid reabsorption. The antiobesity effect of the ChrSd diet appears to be related to expression of adipogenesis- and inflammation-related genes in adipose tissue. These findings suggest that flavonoid-rich Chardonnay grape seed flour induced cholesterol-lowering, antiobesity, and anti-inflammatory health benefits and attenuation of hepatic steatosis via regulation of gene expression related to cholesterol, bile acid, and lipid metab. in liver and adipose tissue.
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  115. 115
    Seo, K.-H.; Bartley, G. E.; Tam, C.; Kim, H.-S.; Kim, D.-H.; Chon, J.-W.; Kim, H.; Yokoyama, W. Chardonnay Grape Seed Flour Ameliorates Hepatic Steatosis and Insulin Resistance via Altered Hepatic Gene Expression for Oxidative Stress, Inflammation, and Lipid and Ceramide Synthesis in Diet-Induced Obese Mice. PLoS One 2016, 11 (12), e0167680– e0167680,  DOI: 10.1371/journal.pone.0167680
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    115
    Chardonnay grape seed flour ameliorates hepatic steatosis and insulin resistance via altered hepatic gene expression for oxidative stress, inflammation, and lipid and ceramide synthesis in diet-induced obese mice
    Seo, Kun-Ho; Bartley, Glenn E.; Tam, Christina; Kim, Hong-Seok; Kim, Dong-Hyeon; Chon, Jung-Whan; Kim, Hyunsook; Yokoyama, Wallace
    PLoS One (2016), 11 (12), e0167680/1-e0167680/20CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)
    To identify differentially expressed hepatic genes contributing to the improvement of high-fat (HF) diet-induced hepatic steatosis and insulin resistance following supplementation of partially defatted flavonoid-rich Chardonnay grape seed flour (ChrSd), diet-induced obese (DIO) mice were fed HF diets contg. either ChrSd or microcryst. cellulose (MCC, control) for 5 wk. The 2-h insulin area under the curve was significantly lowered by ChrSd, indicating that ChrSd improved insulin sensitivity. ChrSd intake also significantly reduced body wt. gain, liver and adipose tissue wt., hepatic lipid content, and plasma low-d. lipoprotein (LDL)-cholesterol, despite a significant increase in food intake. Exon microarray anal. of hepatic gene expression revealed down-regulation of genes related to triglyceride and ceramide synthesis, immune response, oxidative stress, and inflammation and upregulation of genes related to fatty acid oxidn., cholesterol, and bile acid synthesis. In conclusion, the effects of ChrSd supplementation in a HF diet on wt. gain, insulin resistance, and progression of hepatic steatosis in DIO mice were assocd. with modulation of hepatic genes related to oxidative stress, inflammation, ceramide synthesis, and lipid and cholesterol metab.
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    Kim, H.; Kim, D.-H.; Seo, K.-h.; Chon, J.-W.; Nah, S.-Y.; Bartley, G. E.; Arvik, T.; Lipson, R.; Yokoyama, W. Modulation of the Intestinal Microbiota Is Associated with Lower Plasma Cholesterol and Weight Gain in Hamsters Fed Chardonnay Grape Seed Flour. J. Agric. Food Chem. 2015, 63 (5), 1460– 1467,  DOI: 10.1021/jf5026373
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    Modulation of the Intestinal Microbiota Is Associated with Lower Plasma Cholesterol and Weight Gain in Hamsters Fed Chardonnay Grape Seed Flour
    Kim, Hyunsook; Kim, Dong-Hyeon; Seo, Kun-ho; Chon, Jung-Whan; Nah, Seung-Yeol; Bartley, Glenn E.; Arvik, Torey; Lipson, Rebecca; Yokoyama, Wallace
    Journal of Agricultural and Food Chemistry (2015), 63 (5), 1460-1467CODEN: JAFCAU; ISSN:0021-8561. (American Chemical Society)
    The relationship between the intestinal microbiota and the hypocholesterolemic and antiobesity effects of whole grape seed flour from white and red winemaking was evaluated. Male Golden Syrian hamsters were fed a high-fat (HF) control diet or a HF diet supplemented with 10% partially defatted grape seed flours from either Chardonnay (ChrSd) or Cabernet Sauvignon (CabSd) grapes for 3 wk. The nos. of total bacteria and relative abundances of Bifidobacterium spp., Lactobacillus spp., and Firmicutes in feces were significantly lower, while the relative abundance of Bacteroides fragilis was greater than the control from feeding the ChrSd diet. The ratio of Firmicutes/Bacteroidetes (F/B) was lower in the ChrSd diet. There were significantly pos. correlations between Lactobacillus spp., ratio of F/B, and plasma total- and LDL-cholesterol and liver wt. The redn. of Lactobacillus spp. by the ChrSd diet was accompanied by inhibition of Farnesoid X receptor (FXR) signaling in the intestine as expression of intestinal fibrablast growth factor (FGF)15, pos. regulated by FXR, was decreased. Expression of CYP7A1, neg. regulated by FGF15, was up-regulated in the liver, which indicates that alteration of the intestinal microbiota may regulate bile acid and lipid metab. These findings suggest that beneficial health effects of Chardonnay grape seed flour on HF-induced metabolic disease relate in part to modulation of intestinal microbiota and their metabolic processes.
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    Pushpass, R.-A. G.; Alzoufairi, S.; Jackson, K. G.; Lovegrove, J. A. Circulating bile acids as a link between the gut microbiota and cardiovascular health: impact of prebiotics, probiotics and polyphenol-rich foods. Nutrition Research Reviews 2021, 1– 20,  DOI: 10.1017/S0954422421000081
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    Khare, A.; Gaur, S. Cholesterol-Lowering Effects of Lactobacillus Species. Curr. Microbiol. 2020, 77 (4), 638– 644,  DOI: 10.1007/s00284-020-01903-w
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    Cholesterol-Lowering Effects of Lactobacillus Species
    Khare, Aditi; Gaur, Smriti
    Current Microbiology (2020), 77 (4), 638-644CODEN: CUMIDD; ISSN:0343-8651. (Springer)
    Abstr.: Probiotics are the living and non-pathogenic microbial supplements which, upon administration in adequate quantities, influence the host organism pos. by improving gut health and enhancing intestinal mucosal integrity. They suppress potentially pathogenic microorganisms by competing with them for nutrients as well as space for gut adherence. Lactobacillus species are the most commonly used bacteria in the probiotic prepns. and studies show that they have cholesterol-lowering effects on the hosts. Lipids are biol. mols. that are insol. in water and bile salts play a major role in their digestion as they are synthesized and conjugated to taurine or glycine in the liver. Bile salt hydrolase deconjugates taurine or glycine from bile salts. Cholesterol metab. is influenced by the effect of Lactobacillus species on microbial populations as well as overall metabolic activity of human intestinal microflora. Deconjugation of bile salt, concn. of short-chain fatty acids and molar proportion of propionate constitute the major processes by which cholesterol lowering is brought about by Lactobacillus species. This review summarizes the cholesterol-lowering properties of this species. A significant no. of Lactobacillus strains have been known to display substantial bile salt hydrolase activities and identifying those strains for use in therapeutic purposes can be a great advancement. Here, this identification is done using phylogenetic relationship for different identified potential probiotic Lactobacillus strains.
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    Tang, W. H. W.; Backhed, F.; Landmesser, U.; Hazen, S. L. Intestinal Microbiota in Cardiovascular Health and Disease: JACC State-of-the-Art Review. J. Am. Coll Cardiol 2019, 73 (16), 2089– 2105,  DOI: 10.1016/j.jacc.2019.03.024
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    Intestinal Microbiota in Cardiovascular Health and Disease: JACC State-of-the-Art Review
    Tang W H Wilson; Backhed Fredrik; Landmesser Ulf; Hazen Stanley L
    Journal of the American College of Cardiology (2019), 73 (16), 2089-2105 ISSN:.
    Despite major strides in reducing cardiovascular disease (CVD) burden with modification of classic CVD risk factors, significant residual risks remain. Recent discoveries that linked intestinal microbiota and CVD have broadened our understanding of how dietary nutrients may affect cardiovascular health and disease. Although next-generation sequencing techniques can identify gut microbial community participants and provide insights into microbial composition shifts in response to physiological responses and dietary exposures, provisions of prebiotics or probiotics have yet to show therapeutic benefit for CVD. Our evolving understanding of intestinal microbiota-derived physiological modulators (e.g., short-chain fatty acids) and pathogenic mediators (e.g., trimethylamine N-oxide) of host disease susceptibility have created novel potential therapeutic opportunities for improved cardiovascular health. This review discusses the roles of human intestinal microbiota in normal physiology, their associations with CVD susceptibilities, and the potential of modulating intestinal microbiota composition and metabolism as a novel therapeutic target for CVD.
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    Yang, T.; Zubcevic, J. Gut–Brain Axis in Regulation of Blood Pressure. Front Physiol 2017, 8, 845,  DOI: 10.3389/fphys.2017.00845
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    Gut-Brain Axis in Regulation of Blood Pressure
    Yang Tao; Zubcevic Jasenka
    Frontiers in physiology (2017), 8 (), 845 ISSN:1664-042X.
    Hypertension (HTN) is an escalating health issue worldwide. It is estimated that 1.56 billion people will suffer from high blood pressure (BP) by 2025. Recent studies reported an association between gut dysbiosis and HTN, thus proposing interesting avenues for novel treatments of this condition. The sympathetic nervous system (SNS) and the immune system (IS) play a recognized role in the onset and progression of HTN, while reciprocal communication between gut microbiota and the brain can regulate BP by modulating the interplay between the IS and SNS. This review presents the current state of the science implicating brain-gut connection in HTN, highlighting potential pathways of their interaction in control of BP.
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    Kim, D. J.; Chung, H.; Ji, S. C.; Lee, S.; Yu, K.-S.; Jang, I.-J.; Cho, J.-Y. Ursodeoxycholic acid exerts hepatoprotective effects by regulating amino acid, flavonoid, and fatty acid metabolic pathways. Metabolomics 2019, 15 (3), 30,  DOI: 10.1007/s11306-019-1494-5
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    Ursodeoxycholic acid exerts hepatoprotective effects by regulating amino acid, flavonoid, and fatty acid metabolic pathways
    Kim Da Jung; Chung Hyewon; Ji Sang Chun; Lee SeungHwan; Yu Kyung-Sang; Jang In-Jin; Cho Joo-Youn; Chung Hyewon
    Metabolomics : Official journal of the Metabolomic Society (2019), 15 (3), 30 ISSN:.
    INTRODUCTION: Ursodeoxycholic acid (UDCA) is an intestinal bacterial metabolite with hepatoprotective effects. However, molecular mechanisms underlying its effects remain unclear. OBJECTIVES: The aim of this study was to investigate the mechanisms underlying the therapeutic effects of UDCA by using global metabolomics analyses in healthy subjects. METHODS: Healthy Korean men were administered UDCA at dosage of 400, 800, or 1200 mg daily for 2 weeks. Serum samples were collected and used for liver function tests and to determine miR-122 expression levels. Urinary and plasma global metabolomics analyses were conducted using a liquid chromatography system coupled with quadrupole-time-of-flight mass spectrometry (LC/QTOFMS) and gas chromatography-TOFMS (GC/TOFMS). Unsupervised multivariate analysis (principal component analysis) was performed to identify discriminative markers before and after treatment. RESULTS: Alanine transaminase score and serum miR-122 levels decreased significantly after 2 weeks of treatment. Through LC- and GC-based metabolomic profiling, we identified 40 differential metabolites in plasma and urine samples. CONCLUSIONS: Regulation of liver function scores and metabolic alternations highlight the potential hepatoprotective action of UDCA, which were primarily associated with amino acid, flavonoid, and fatty acid metabolism in healthy men.
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  122. 122
    Nogal, A.; Valdes, A. M.; Menni, C. The role of short-chain fatty acids in the interplay between gut microbiota and diet in cardio-metabolic health. Gut Microbes 2021, 13 (1), 1897212,  DOI: 10.1080/19490976.2021.1897212
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    122
    The role of short-chain fatty acids in the interplay between gut microbiota and diet in cardio-metabolic health
    Nogal, Ana; Valdes, Ana M.; Menni, Cristina
    Gut Microbes (2021), 13 (1), 1897212/1-1897212/24CODEN: GMUIA4; ISSN:1949-0984. (Taylor & Francis, Inc.)
    A review. The gut microbiota plays an important role in cardio-metabolic diseases with diet being among the strongest modulators of gut microbiota compn. and function. Resistant dietary carbohydrates are fermented to short-chain fatty acids (SCFAs) by the gut bacteria. Fiber and omega-3 rich diets increase SCFAs prodn. and abundance of SCFA-producing bacteria. Likewise, SCFAs can improve gut barrier integrity, glucose, and lipid metab., regulate the immune system, the inflammatory response, and blood pressure. Therefore, targeting the gut microbiota with dietary strategies leading to increased SCFA prodn. may benefit cardio-metabolic health. In this review, we provide an overview of the assocn. between diet, SCFAs produced by the gut microbiota and cardio-metabolic diseases. We first discuss the assocn. between the human gut microbiota and cardio-metabolic diseases, then investigate the role of SCFAs and finally explore the beneficial effects of specific dietary interventions that can improve cardio-metabolic outcomes through boosting the SCFA prodn.
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  123. 123
    Singh, J.; Metrani, R.; Shivanagoudra, S. R.; Jayaprakasha, G. K.; Patil, B. S. Review on Bile Acids: Effects of the Gut Microbiome, Interactions with Dietary Fiber, and Alterations in the Bioaccessibility of Bioactive Compounds. J. Agric. Food Chem. 2019, 67 (33), 9124– 9138,  DOI: 10.1021/acs.jafc.8b07306
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    123
    Review on Bile Acids: Effects of the Gut Microbiome, Interactions with Dietary Fiber, and Alterations in the Bioaccessibility of Bioactive Compounds
    Singh, Jashbir; Metrani, Rita; Shivanagoudra, Siddanagouda R.; Jayaprakasha, Guddadarangavvanahally K.; Patil, Bhimanagouda S.
    Journal of Agricultural and Food Chemistry (2019), 67 (33), 9124-9138CODEN: JAFCAU; ISSN:0021-8561. (American Chemical Society)
    A review. Bile acids are cholesterol-derived steroid mols. that serve various metabolic functions, particularly in the digestion of lipids. Gut microbes produce unconjugated and secondary bile acids through deconjugation and dehydroxylation reactions, resp. Alterations in the gut microbiota have profound effects on bile acid metab., which can result in the development of gastrointestinal and metabolic diseases. Emerging research shows that diets rich in dietary fiber have substantial effects on the microbiota and human health. Plant-based foods are primary sources of bioactive compds. and dietary fiber, which are metabolized by microbes to produce different metabolites. However, the bioaccessibility of these compds. are not well-defined. In this review, we discuss the interaction of bile acids with dietary fiber, the gut microbiota, and their role in the bioaccessibility of bioactive compds. To understand the possible mechanism by which bile acids bind fiber, mol. docking was performed between different dietary fiber and bile salts.
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  124. 124
    Lucas, L. N.; Barrett, K.; Kerby, R. L.; Zhang, Q.; Cattaneo, L. E.; Stevenson, D.; Rey, F. E.; Amador-Noguez, D. Dominant Bacterial Phyla from the Human Gut Show Widespread Ability To Transform and Conjugate Bile Acids. mSystems 2021, 6, e00805-21  DOI: 10.1128/mSystems.00805-21
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    Ngamukote, S.; Mäkynen, K.; Thilawech, T.; Adisakwattana, S. Cholesterol-Lowering Activity of the Major Polyphenols in Grape Seed. Molecules 2011, 16 (6), 5054– 5061,  DOI: 10.3390/molecules16065054
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    125
    Cholesterol-lowering activity of the major polyphenols in grape seed
    Ngamukote, Sathaporn; Makynen, Kittana; Thilawech, Thavaree; Adisakwattana, Sirichai
    Molecules (2011), 16 (), 5054-5061CODEN: MOLEFW; ISSN:1420-3049. (MDPI AG)
    The major polyphenols in grape seed have been shown to have beneficial health effects in the prevention of dyslipidemia and cardiovascular diseases. In this present study, we investigated the cholesterol-lowering activity of three major polyphenolic compds. found in grape seed. The results showed that gallic acid, catechin, and epicatechin significantly inhibited pancreatic cholesterol esterase in a concn.-dependent manner. Moreover, they bound to taurocholic acid, taurodeoxycholic acid, and glycodeoxycholic acid at levels ranging from 38.6% to 28.2%. At the concn. of 0.2 mg/mL, gallic acid, catechin, and epicatechin reduced the formation of cholesterol micelles 27.26 ± 2.17 %, 11.88 ± 0.75 %, and 19.49 ± 3.71 %, resp. These findings clearly demonstrate that three major polyphenolic compds. present in a particular grape seed have cholesterol-lowering activity by inhibiting pancreatic cholesterol esterase, binding of bile acids, and reducing soly. of cholesterol in micelles which may result in delayed cholesterol absorption.
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  126. 126
    Appel, L. J.; Sacks, F. M.; Carey, V. J.; Obarzanek, E.; Swain, J. F.; Miller, E. R.; Conlin, P. R.; Erlinger, T. P.; Rosner, B. A.; Laranjo, N. M.; Charleston, J.; McCarron, P.; Bishop, L. M.; OmniHeart Collaborative Research Group Effects of Protein, Monounsaturated Fat, and Carbohydrate Intake on Blood Pressure and Serum LipidsResults of the OmniHeart Randomized Trial. JAMA 2005, 294 (19), 2455– 2464,  DOI: 10.1001/jama.294.19.2455
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    126
    Effects of protein, monounsaturated fat and carbohydrate intake on blood pressure and serum lipids. Results of the OmniHeart Randomized trial
    Appel, Lawrence J.; Sacks, Frank M.; Carety, Frank M.; Carey, Vincent J.; Obarzanek, Eva; Swain, Janis F.; Miller, Edgar R.; Colin, Paul R.; Erlinger, Thomas P.; Rosner, Bernard A.; Laranjo, Nancy M.; Charleston, Jeanne; McCarron, Phyllis; Alexander, Natalie; Carrington, Cassandra; Jenson, Kimberly; Hamilton, Eileen; McCarthy, Scott; Rodek, Rachel; Stebbins, David; Widican, Kristen; Yee, Karen; McEnery-Stonelake, Melissa; Ange, Brett; Brode, Cassie; Bryant, Kimberly; George, Toya; Green, Mildren; Greene, Ella; Griffin, Ronea; Harrison, Tara; Jiggets, Brittany; Lally, Theresa; Lawrence, Gloria; McCully, Karen; Monnett, Denise; Myer, Mary; Owens, Dana; Pearson, Rosetta; Peterson, Joy; Powell, Charles; Smith, Jennifer; Summers, Amber; Tankard, Lindsay; Thomas, Letitia; White, Karen; Wilkie, Essie; Phillips, Katherine; Bittner, Jennifer; Proschan, Michael
    JAMA, the Journal of the American Medical Association (2005), 294 (19), 2455-2464CODEN: JAMAAP; ISSN:0098-7484. (American Medical Association)
    Context: Reduced intake of satd. fat is widely recommended for prevention of cardiovascular disease. The type of macronutrient that should replace satd. fat remains uncertain. Objective: To compare the effects of 3 healthful diets, each with reduced satd. fat intake, on blood pressure and serum lipids. Design, Setting, and Participants: Randomized, 3-period, crossover feeding study (Apr. 2003 to June 2005) conducted in Baltimore, Md, and Boston, Mass. Participants were 164 adults with prehypertension or stage 1 hypertension. Each feeding period lasted 6 wk and body wt. was kept const. Interventions: A diet rich in carbohydrates; a diet rich in protein, about half from plant sources; and a diet rich in unsatd. fat, predominantly monounsatd. fat. Main Outcome Measures: Systolic blood pressure and low-d. lipoprotein cholesterol. Results: Blood pressure, low-d. lipoprotein cholesterol, and estd. coronary heart disease risk were lower on each diet compared with baseline. Compared with the carbohydrate diet, the protein diet further decreased mean systolic blood pressure by 1.4 mm Hg (P = .002) and by 3.5 mm Hg (P = .006) among those with hypertension and decreased low-d. lipoprotein cholesterol by 3.3 mg/dL (0.09 mmol/L; P = .01), high-d. lipoprotein cholesterol by 1.3 mg/dL (0.03 mmol/L; P = .02), and triglycerides by 15.7 mg/dL (0.18 mmol/L; P < .001). Compared with the carbohydrate diet, the unsatd. fat diet decreased systolic blood pressure by 1.3 mm Hg (P = .005) and by 2.9 mm Hg among those with hypertension (P = .02), had no significant effect on low-d. lipoprotein cholesterol, increased high-d. lipoprotein cholesterol by 1.1 mg/dL (0.03 mmol/L; P = .03), and lowered triglycerides by 9.6 mg/dL (0.11 mmol/L; P = .02). Compared with the carbohydrate diet, estd. 10-yr coronary heart disease risk was lower and similar on the protein and unsatd. fat diets. Conclusion: In the setting of a healthful diet, partial substitution of carbohydrate with either protein or monounsatd. fat can further lower blood pressure, improve lipid levels, and reduce estd. cardiovascular risk.
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  127. 127
    Mueller, N. T.; Zhang, M.; Juraschek, S. P.; Miller, E. R., 3rd; Appel, L. J. Effects of high-fiber diets enriched with carbohydrate, protein, or unsaturated fat on circulating short chain fatty acids: results from the OmniHeart randomized trial. American Journal of Clinical Nutrition 2020, 111 (3), 545– 554,  DOI: 10.1093/ajcn/nqz322
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    127
    Effects of high-fiber diets enriched with carbohydrate, protein, or unsaturated fat on circulating short chain fatty acids: results from the OmniHeart randomized trial
    Mueller Noel T; Zhang Mingyu; Appel Lawrence J; Mueller Noel T; Miller Edgar R; Appel Lawrence J; Juraschek Stephen P
    The American journal of clinical nutrition (2020), 111 (3), 545-554 ISSN:.
    BACKGROUND: Short chain fatty acids (SCFAs; e.g., acetate, propionate, and butyrate) are produced by microbial fermentation of fiber in the colon. Evidence is lacking on how high-fiber diets that differ in macronutrient composition affect circulating SCFAs. OBJECTIVES: We aimed to compare the effects of 3 high-fiber isocaloric diets differing in %kcal of carbohydrate, protein, or unsaturated fat on circulating SCFAs. Based on previous literature, we hypothesized that serum acetate, the main SCFA in circulation, increases on all high-fiber diets, but differently by macronutrient composition of the diet. METHODS: OmniHeart is a randomized crossover trial of 164 men and women (≥30 y old); 163 participants with SCFA data were included in this analysis. We provided participants 3 isocaloric high-fiber (∼30 g/2100 kcal) diets, each for 6 wk, in random order: a carbohydrate-rich (Carb) diet, a protein-rich (Prot) diet (protein predominantly from plant sources), and an unsaturated fat-rich (Unsat) diet. We used LC-MS to quantify SCFA concentrations in fasting serum, collected at baseline and the end of each diet period. We fitted linear regression models with generalized estimating equations to examine change in ln-transformed SCFAs from baseline to the end of each diet; differences between diets; and associations of changes in SCFAs with cardiometabolic parameters. RESULTS: From baseline, serum acetate concentrations were increased by the Prot (β: 0.24; 95% CI: 0.12, 0.35), Unsat (β: 0.21; 95% CI: 0.10, 0.33), and Carb (β: 0.12; 95% CI: 0.01, 0.24) diets; between diets, only Prot compared with Carb was significant (P = 0.02). Propionate was decreased by the Carb (β: -0.10; 95% CI: -0.16, -0.03) and Unsat (β: -0.10; 95% CI: -0.16, -0.04) diets, not the Prot diet; between diet comparisons of Carb vs. Prot (P = 0.006) and Unsat vs. Prot (P = 0.002) were significant. The Prot diet increased butyrate (β: 0.05; 95% CI: 0.00, 0.09) compared with baseline, but not compared with the other diets. Increases in acetate were associated with decreases in insulin and glucose; increases in propionate with increases in leptin, LDL cholesterol, and blood pressure; and increases in butyrate with increases in insulin and glucose, and decreases in HDL cholesterol and ghrelin (Ps < 0.05). CONCLUSIONS: Macronutrient composition of high-fiber diets affects circulating SCFAs, which are associated with measures of appetite and cardiometabolic health. This trial was registered at clinicaltrials.gov as NCT00051350.
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  128. 128
    Müller, M.; Hernández, M. A. G.; Goossens, G. H.; Reijnders, D.; Holst, J. J.; Jocken, J. W. E.; van Eijk, H.; Canfora, E. E.; Blaak, E. E. Circulating but not faecal short-chain fatty acids are related to insulin sensitivity, lipolysis and GLP-1 concentrations in humans. Sci. Rep. 2019, 9 (1), 12515,  DOI: 10.1038/s41598-019-48775-0
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    Dumitrescu, L.; Marta, D.; Danau, A.; Lefter, A.; Tulba, D.; Cozma, L.; Manole, E.; Gherghiceanu, M.; Ceafalan, L. C.; Popescu, B. O. Serum and Fecal Markers of Intestinal Inflammation and Intestinal Barrier Permeability Are Elevated in Parkinson’s Disease. Front Neurosci 2021, 15, 689723,  DOI: 10.3389/fnins.2021.689723
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    129
    Serum and Fecal Markers of Intestinal Inflammation and Intestinal Barrier Permeability Are Elevated in Parkinson's Disease
    Dumitrescu Laura; Danau Adela; Lefter Antonia; Tulba Delia; Cozma Liviu; Popescu Bogdan Ovidiu; Dumitrescu Laura; Danau Adela; Lefter Antonia; Tulba Delia; Cozma Liviu; Popescu Bogdan Ovidiu; Marta Daciana; Manole Emilia; Gherghiceanu Mihaela; Ceafalan Laura Cristina; Popescu Bogdan Ovidiu; Manole Emilia; Gherghiceanu Mihaela; Ceafalan Laura Cristina
    Frontiers in neuroscience (2021), 15 (), 689723 ISSN:1662-4548.
    Parkinson's disease (PD) is characterized by alpha-synuclein misfolding with subsequent intraneuronal amyloid formation and accumulation, low grade neuroinflammatory changes, and selective neurodegeneration. Available evidence suggests that the pathology usually begins in the gut and olfactory mucosa, spreading to the brain via the vagus and olfactory nerves, by a prion-like mechanism. A causal relationship has not been established, but gut dysbiosis is prevalent in PD and may lead to intestinal inflammation and barrier dysfunction. Additionally, epidemiological data indicate a link between inflammatory bowel diseases and PD. Calprotectin and zonulin are markers of intestinal inflammation and barrier permeability, respectively. We evaluated their serum and fecal levels in 22 patients with sporadic PD and 16 unmatched healthy controls. Mean calprotectin was higher in PD, both in serum (14.26 mcg/ml ± 4.50 vs. 5.94 mcg/ml ± 3.80, p = 0.0125) and stool (164.54 mcg/g ± 54.19 vs. 56.19 mcg/g ± 35.88, p = 0.0048). Mean zonulin was also higher in PD serum (26.69 ng/ml ± 3.55 vs. 19.43 ng/ml ± 2.56, p = 0.0046) and stool (100.19 ng/ml ± 28.25 vs. 37.3 ng/ml ± 13.26, p = 0.0012). Calprotectin was above the upper reference limit in 19 PD serums and 6 controls (OR = 10.56, 95% CI = 2.17-51.42, p = 0.0025) and in 20 PD stool samples and 4 controls (OR = 30, 95% CI = 4.75-189.30, p = 0.000045). Increased zonulin was found only in the stool samples of 8 PD patients. Despite the small sample size, our findings are robust, complementing and supporting other recently published results. The relation between serum and fecal calprotectin and zonulin levels and sporadic PD warrants further investigation in larger cohorts.
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  130. 130
    Chen, S.-J.; Chen, C.-C.; Liao, H.-Y.; Lin, Y.-T.; Wu, Y.-W.; Liou, J.-M.; Wu, M.-S.; Kuo, C.-H.; Lin, C.-H. Association of Fecal and Plasma Levels of Short-Chain Fatty Acids With Gut Microbiota and Clinical Severity in Patients With Parkinson Disease. Neurology 2022, 98 (8), e848– e858,  DOI: 10.1212/WNL.0000000000013225
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    130
    Association of Fecal and Plasma Levels of Short-Chain Fatty Acids With Gut Microbiota and Clinical Severity in Patients With Parkinson Disease
    Chen, Szu-Ju; Chen, Chieh-Chang; Liao, Hsin-Yu; Lin, Ya-Ting; Wu, Yu-Wei; Liou, Jyh-Ming; Wu, Ming-Shiang; Kuo, Ching-Hua; Lin, Chin-Hsien
    Neurology (2022), 98 (8), e848-e858CODEN: NEURAI; ISSN:0028-3878. (Wolters Kluwer)
    Short-chain fatty acids (SCFAs) are gut microbial metabolites that promote the disease process in a rodent model of Parkinson disease (PD), but fecal levels of SCFAs in patients with PD are reduced. Simultaneous assessments of fecal and plasma SCFA levels, and their interrelationships with the PD disease process, are scarce. We aimed to compare fecal and plasma levels of different SCFA subtypes in patients with PD and healthy controls to delineate their interrelations and link to gut microbiota changes and clin. severity of PD. A cohort of 96 patients with PD and 85 controls were recruited from National Taiwan University Hospital. Fecal and plasma concns. of SCFAs were measured using chromatog. and mass spectrometry. Gut microbiota was analyzed using metagenomic shotgun sequencing. Body mass index and medical comorbidities were evaluated and dietary information was obtained using a food frequency questionnaire. To assess motor and cognitive impairment, we used the Movement Disorder Society-Unified Parkinsons Disease Rating Scale (MDS-UPDRS) and the Mini-Mental Status Examn. (MMSE). Compared with controls, patients with PD had lower fecal but higher plasma concns. of acetate, propionate, and butyrate. After adjustment for age, sex, disease duration, and anti-PD medication dosage, MDS-UPDRS part III motor scores correlated with reduced fecal levels of acetate (ρ = -0.37, p = 0.012), propionate (ρ = -0.32, p = 0.036), and butyrate (ρ = -0.40, p = 0.004) and with increased plasma propionate concns. (ρ = 0.26, p = 0.042) in patients with PD. MMSE scores neg. correlated with plasma levels of butyrate (ρ = -0.09, p = 0.027) and valerate (ρ = -0.032, p = 0.033) after adjustment for confounders. SCFAs-producing gut bacteria correlated pos. with fecal levels of SCFAs in healthy controls but revealed no assocn. in patients with PD. In the PD patient group, the abundance of proinflammatory microbes, such as Clostridiales bacterium NK3B98 and Ruminococcus sp AM07-15, significantly correlated with decreased fecal levels and increased plasma levels of SCFAs, esp. propionic acid. Redns. in fecal SCFAs but increased plasma SCFAs were obsd. in patients with PD and corelated to specific gut microbiota changes and the clin. severity of PD. This study provides Class III evidence that gut metabolite SCFAs distinguish between patients with PD and controls and are assocd. with disease severity in patients with PD.
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  131. 131
    Taladrid, D.; de Celis, M.; Belda, I.; Bartolome, B.; Moreno-Arribas, M. V. Hypertension- and glycaemia-lowering effects of a grape-pomace-derived seasoning in high-cardiovascular risk and healthy subjects. Interplay with the gut microbiome. Food Funct 2022, 13 (4), 2068– 2082,  DOI: 10.1039/D1FO03942C
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    131
    Hypertension- and glycaemia-lowering effects of a grape-pomace-derived seasoning in high-cardiovascular risk and healthy subjects. Interplay with the gut microbiome
    Taladrid, Diego; de Celis, Miguel; Belda, Ignacio; Bartolome, Begona; Moreno-Arribas, M. Victoria
    Food & Function (2022), 13 (4), 2068-2082CODEN: FFOUAI; ISSN:2042-6496. (Royal Society of Chemistry)
    Grape pomace (GP) is a winery byproduct rich in polyphenols and dietary fiber. Some recent results suggest that GP-derived exts. could be promising additives in food, specially recommended for low-salt diets. The hypothesis tested in this paper is that the regular consumption of GP-derived seasonings could help in the control of hypertension and glycemia. A randomized intervention study (6 wk) was performed in high-risk cardiovascular subjects (n = 17) and in healthy subjects (n = 12) that were randomly allocated into intervention (2 g day-1 of GP seasoning) or control (no seasoning consumed) groups. Blood samples, faeces, urine and blood pressure (BP) were taken at the baseline and at the end of the intervention. Faecal samples were analyzed for microbiota compn. (16S rRNA gene sequencing) and microbial-derived metabolites (short chain fatty acids and phenolic metabolites). Among the clin. parameters studied, BP and fasting blood glucose significantly decreased (p < 0.05) after the seasoning intervention, but not for the control group. Notably, application of a novel approach based on ASV (Amplicon Sequence Variant) co-occurrence networks allowed us to identify some bacterial communities whose relative abundances were related with metadata. Our primary findings suggest that GP-seasoning may help in the modulation of cardiometabolic risk factors, mainly in the early stages. Furthermore, it evidences modulation of gut microbiota and functional bacterial communities by grape pomace, which might mediate the cardiometabolic effects of this byproduct.
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    Agus, A.; Clément, K.; Sokol, H. Gut microbiota-derived metabolites as central regulators in metabolic disorders. Gut 2021, 70 (6), 1174– 1182,  DOI: 10.1136/gutjnl-2020-323071
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    132
    Gut microbiota-derived metabolites as central regulators in metabolic disorders
    Agus, Allison; Clement, Karine; Sokol, Harry
    Gut (2021), 70 (6), 1174-1182CODEN: GUTTAK; ISSN:0017-5749. (BMJ)
    A review. Metabolic disorders represent a growing worldwide health challenge due to their dramatically increasing prevalence. The gut microbiota is a crucial actor that can interact with the host by the prodn. of a diverse reservoir of metabolites, from exogenous dietary substrates or endogenous host compds. Metabolic disorders are assocd. with alterations in the compn. and function of the gut microbiota. Specific classes of microbiota-derived metabolites, notably bile acids, short-chain fatty acids, branched-chain amino acids, trimethylamine N-oxide, tryptophan and indole derivs., have been implicated in the pathogenesis of metabolic disorders. This review aims to define the key classes of microbiota-derived metabolites that are altered in metabolic diseases and their role in pathogenesis. They represent potential biomarkers for early diagnosis and prognosis as well as promising targets for the development of novel therapeutic tools for metabolic disorders.
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    Martínez-Maqueda, D.; Zapatera, B.; Gallego-Narbón, A.; Vaquero, M. P.; Saura-Calixto, F.; Pérez-Jiménez, J. A 6-week supplementation with grape pomace to subjects at cardiometabolic risk ameliorates insulin sensitivity, without affecting other metabolic syndrome markers. Food & Function 2018, 9 (11), 6010– 6019,  DOI: 10.1039/C8FO01323C
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    133
    A 6-week supplementation with grape pomace to subjects at cardiometabolic risk ameliorates insulin sensitivity, without affecting other metabolic syndrome markers
    Martinez-Maqueda, Daniel; Zapatera, Belen; Gallego-Narbon, Angelica; Vaquero, M. Pilar; Saura-Calixto, Fulgencio; Perez-Jimenez, Jara
    Food & Function (2018), 9 (11), 6010-6019CODEN: FFOUAI; ISSN:2042-6496. (Royal Society of Chemistry)
    Grape polyphenols have shown a promising role in the modulation of metabolic syndrome (MetS), mostly in animal models. However, clin. studies are scarce and they usually only consider a fraction of polyphenols, ignoring the non-extractable polyphenols (high mol. wt. compds. or assocd. with macromols. such as dietary fiber). This study aimed at evaluating the effect of grape pomace, rich in both extractable and non-extractable polyphenols, on markers of MetS. Fifty subjects (22 women) aged 20-65 with at least two MetS factors were randomly assigned to the product (daily dose of 8 g of dried grape pomace) or to the control group in a 6 wk crossover design with a 4 wk wash-out. Samples were collected at the beginning and at the end of both periods; half of the participants were subjected to an oral glucose tolerance test at the beginning and the end of the supplementation period. Grape pomace supplementation significantly improved fasting insulinemia (p < 0.01), without affecting other cardiometabolic risk parameters. A tendency towards an improvement in postprandial insulinemia was obsd., particularly in those subjects with higher fasting insulin levels. Therefore, supplementation with grape pomace may be a strategy for improving insulin sensitivity in subjects at high cardiometabolic risk.
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    Ramos-Romero, S.; Martínez-Maqueda, D.; Hereu, M.; Amézqueta, S.; Torres, J. L.; Pérez-Jiménez, J. Modifications of Gut Microbiota after Grape Pomace Supplementation in Subjects at Cardiometabolic Risk: A Randomized Cross-Over Controlled Clinical Trial. Foods (Basel, Switzerland) 2020, 9 (9), 1279,  DOI: 10.3390/foods9091279
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    Koudoufio, M.; Desjardins, Y.; Feldman, F.; Spahis, S.; Delvin, E.; Levy, E. Insight into Polyphenol and Gut Microbiota Crosstalk: Are Their Metabolites the Key to Understand Protective Effects against Metabolic Disorders?. Antioxidants 2020, 9 (10), 982,  DOI: 10.3390/antiox9100982
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    135
    Insight into polyphenol and gut microbiota crosstalk: are their metabolites the key to understand protective effects against metabolic disorders
    Koudoufio, Mireille; Desjardins, Yves; Feldman, Francis; Spahis, Schohraya; Delvin, Edgard; Levy, Emile
    Antioxidants (2020), 9 (10), 982CODEN: ANTIGE; ISSN:2076-3921. (MDPI AG)
    A review lifestyle factors, esp. diet and nutrition, are currently regarded as essential avenues to decrease modern-day cardiometabolic disorders (CMD), including obesity, metabolic syndrome, type 2 diabetes, and atherosclerosis. Many groups around the world attribute these trends, at least partially, to bioactive plant polyphenols given their anti-oxidant and anti-inflammatory actions. In fact, polyphenols can prevent or reverse the progression of disease processes through many distinct mechanisms. In particular, the crosstalk between polyphenols and gut microbiota, recently unveiled thanks to DNA-based tools and next generation sequencing, unravelled the central regulatory role of dietary polyphenols and their intestinal micro-ecol. metabolites on the host energy metab. and related illnesses. The objectives of this review are to: provide an understanding of classification, structure, and bioavailability of dietary polyphenols; underline their metab. by gut microbiota; highlight their prebiotic effects on microflora; discuss the multifaceted roles of their metabolites in CMD while shedding light on the mechanisms of action; and underscore their ability to initiate host epigenetic regulation. In sum, the review clearly documents whether dietary polyphenols and micro-ecol. favorably interact to promote multiple physiol. functions on human organism.
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    Dias, R.; Pereira, C. B.; Pérez-Gregorio, R.; Mateus, N.; Freitas, V. Recent advances on dietary polyphenol’s potential roles in Celiac Disease. Trends Food Sci. Tech 2021, 107, 213– 225,  DOI: 10.1016/j.tifs.2020.10.033
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    Recent advances on dietary polyphenol's potential roles in Celiac Disease
    Dias, Ricardo; Pereira, Catarina Bessa; Perez-Gregorio, Rosa; Mateus, Nuno; Freitas, Victor
    Trends in Food Science & Technology (2021), 107 (), 213-225CODEN: TFTEEH; ISSN:0924-2244. (Elsevier Ltd.)
    Over the last years, epidemiol. and population-based studies have suggested that a continuous and prolonged intake of fruits, vegetables and whole-grains - all rich sources of polyphenols -, may contribute to the prevention of age-related chronic diseases. However, conclusive proof and understanding of the health benefits provided by polyphenols on a Celiac Disease framework remain largely unexplored, notwithstanding the unmet need for alternative treatments to a gluten-free diet. Herein, this topic has been thoroughly explored based on the most recent scientific breakthroughs, bringing light into the remarkable potential and mol. mechanisms by which polyphenols may become valuable allies against the cytotoxicity of gluten proteins, based on their ability to interact with and reduce the bioavailability of immunogenic peptides, to counteract oxidative stress and inflammation, to regulate intestinal epithelial barrier integrity and function, to affect the gut microbial ecosystem, and to modulate immune responses. Altogether, this review opens up new horizons concerning the rational development, applicability and/or valorization of polyphenol-rich functional foods by industry as a promising nutritional strategy to manage and prevent Celiac Disease.
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    Liu, C.; Vervoort, J.; Beekmann, K.; Baccaro, M.; Kamelia, L.; Wesseling, S.; Rietjens, I. M. C. M. Interindividual Differences in Human Intestinal Microbial Conversion of (−)-Epicatechin to Bioactive Phenolic Compounds. J. Agric. Food Chem. 2020, 68 (48), 14168– 14181,  DOI: 10.1021/acs.jafc.0c05890
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    Interindividual Differences in Human Intestinal Microbial Conversion of (-)-Epicatechin to Bioactive Phenolic Compounds
    Liu, Chen; Vervoort, Jacques; Beekmann, Karsten; Baccaro, Marta; Kamelia, Lenny; Wesseling, Sebas; Rietjens, Ivonne M. C. M.
    Journal of Agricultural and Food Chemistry (2020), 68 (48), 14168-14181CODEN: JAFCAU; ISSN:0021-8561. (American Chemical Society)
    To quantify interindividual differences in the human intestinal microbial metab. of (-)-epicatechin (EC), in vitro anaerobic incubations with fecal inocula from 24 healthy donors were conducted. EC-derived colonic microbial metabolites were qual. and quantitively analyzed by liq. chromatog. triple quadrupole mass spectrometry (LC-TQ-MS) and liq. chromatog. time-of-flight mass spectrometry (LC-TOF-MS). Quant. microbiota characterization was achieved by 16S rRNA anal. The results obtained show 1-(3',4'-dihydroxyphenyl)-3-(2'',4'',6''-dihydroxyphenyl)-2-propanol (3,4-diHPP-2-ol) and 5-(3',4'-dihydroxyphenyl)-γ-valerolactone (3,4-diHPV) to be key intermediate microbial metabolites of EC and also revealed the substantial interindividual differences in both the rate of EC conversion and the time-dependent EC metabolite pattern. Furthermore, substantial differences in microbiota compn. among different individuals were detected. Correlations between specific microbial phylotypes and formation of certain metabolites were established. It is concluded that interindividual differences in the intestinal microbial metab. of EC may contribute to interindividual differences in potential health effects of EC-abundant dietary foods or drinks.
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    Hollands, W. J.; Philo, M.; Perez-Moral, N.; Needs, P. W.; Savva, G. M.; Kroon, P. A. Monomeric Flavanols Are More Efficient Substrates for Gut Microbiota Conversion to Hydroxyphenyl-γ-Valerolactone Metabolites Than Oligomeric Procyanidins: A Randomized, Placebo-Controlled Human Intervention Trial. Mol. Nutr Food Res. 2020, 64 (10), 1901135,  DOI: 10.1002/mnfr.201901135
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    Monomeric Flavanols Are More Efficient Substrates for Gut Microbiota Conversion to Hydroxyphenyl-γ-Valerolactone Metabolites Than Oligomeric Procyanidins: A Randomized, Placebo-Controlled Human Intervention Trial
    Hollands, Wendy J.; Philo, Mark; Perez-Moral, Natalia; Needs, Paul W.; Savva, George M.; Kroon, Paul A.
    Molecular Nutrition & Food Research (2020), 64 (10), 1901135CODEN: MNFRCV; ISSN:1613-4125. (Wiley-VCH Verlag GmbH & Co. KGaA)
    Scope : The majority of ingested flavanols reach the colon where they are catabolized by the microbiota to form hydroxyphenyl-γ-valerolactones (HGVLs). It is not known if the HGVLs are catabolic products of monomeric (epi)catechins (EPC), oligomeric procyanidins (OPCs), or both. Using data from a randomized, double-blind, placebo-controlled crossover trial the relative contributions of catechins and OPC to the bioavailable pool of HGVLs are estd. Methods and results : Participants ingested an apple ext. once daily for 28 days that delivered the following: i. 70 mg EPC and 65 mg OPC (low dose EPC), ii. 140 mg EPC and 130 mg OPC (high dose EPC), iii. 6 mg EPC and 130 mg OPC (OPC), and iv. a placebo control. Urine is collected over a 24-h period before and after treatments. The median urinary excretion of HGVLs after ingestion of the high dose EPC is tenfold higher than that excreted after ingestion of the OPC that provided an equiv. dose of PC. Approx. 22% of catechins are converted to HGVLs in contrast to PC, for which there is limited conversion. Conclusion : Monomeric catechins are efficiently converted to derived HGVLs that are absorbed and excreted in human urine, whereas oligomeric PCs are much less efficiently converted.
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    Rowland, I.; Gibson, G.; Heinken, A.; Scott, K.; Swann, J.; Thiele, I.; Tuohy, K. Gut microbiota functions: metabolism of nutrients and other food components. European Journal of Nutrition 2018, 57 (1), 1– 24,  DOI: 10.1007/s00394-017-1445-8
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    Gut microbiota functions: metabolism of nutrients and other food components
    Rowland, Ian; Gibson, Glenn; Heinken, Almut; Scott, Karen; Swann, Jonathan; Thiele, Ines; Tuohy, Kieran
    European Journal of Nutrition (2018), 57 (1), 1-24CODEN: EJNUFZ; ISSN:1436-6207. (Springer)
    The diverse microbial community that inhabits the human gut has an extensive metabolic repertoire that is distinct from, but complements the activity of mammalian enzymes in the liver and gut mucosa and includes functions essential for host digestion. As such, the gut microbiota is a key factor in shaping the biochem. profile of the diet and, therefore, its impact on host health and disease. The important role that the gut microbiota appears to play in human metab. and health has stimulated research into the identification of specific microorganisms involved in different processes, and the elucidation of metabolic pathways, particularly those assocd. with metab. of dietary components and some host-generated substances. In the first part of the review, we discuss the main gut microorganisms, particularly bacteria, and microbial pathways assocd. with the metab. of dietary carbohydrates (to short chain fatty acids and gases), proteins, plant polyphenols, bile acids, and vitamins. The second part of the review focuses on the methodologies, existing and novel, that can be employed to explore gut microbial pathways of metab. These include math. models, omics techniques, isolated microbes, and enzyme assays.
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    González-Aguilar, G. A.; Blancas-Benítez, F. J.; Sáyago-Ayerdi, S. G. Polyphenols associated with dietary fibers in plant foods: molecular interactions and bioaccessibility. Curr. Opin Food Sci. 2017, 13, 84– 88,  DOI: 10.1016/j.cofs.2017.03.004
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    Saura-Calixto, F. Concept and Health-Related Properties of Nonextractable Polyphenols: The Missing Dietary Polyphenols. J. Agric. Food Chem. 2012, 60 (45), 11195– 11200,  DOI: 10.1021/jf303758j
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    Concept and Health-Related Properties of Nonextractable Polyphenols: The Missing Dietary Polyphenols
    Saura-Calixto, Fulgencio
    Journal of Agricultural and Food Chemistry (2012), 60 (45), 11195-11200CODEN: JAFCAU; ISSN:0021-8561. (American Chemical Society)
    A review. Most research studies in the field of dietary polyphenols or phenolic compds. use a chem. approach focusing exclusively on polyphenols extd. from plant foods with org. solvents. However, an appreciable part of polyphenols are not extd. with org. solvents and thus are ignored in biol., nutritional, and epidemiol. studies. Recent studies have shown that these nonextractable polyphenols (NEPP) are a major part of total dietary polyphenols and that they exhibit a significant biol. activity. A physiol. approach is proposed on the basis that the bioavailability and health-related properties of polyphenols depend on their soly. in intestinal fluids, which is different from their soly. in org. solvents. An attempt is made to clarify the concept of NEPP, distinguishing between chem. and physiol. approaches and pointing out the main qual. and quant. differences between them. It is stressed that the literature and databases refer to only extractable polyphenols. Greater attention to NEPP may fill the current gap in the field of dietary polyphenols.
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    Eetemadi, A.; Rai, N.; Pereira, B. M. P.; Kim, M.; Schmitz, H.; Tagkopoulos, I. The Computational Diet: A Review of Computational Methods Across Diet, Microbiome, and Health. Front Microbiol 2020, 11, 393,  DOI: 10.3389/fmicb.2020.00393
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    The Computational Diet: A Review of Computational Methods Across Diet, Microbiome, and Health
    Eetemadi Ameen; Kim Minseung; Tagkopoulos Ilias; Eetemadi Ameen; Rai Navneet; Pereira Beatriz Merchel Piovesan; Kim Minseung; Tagkopoulos Ilias; Pereira Beatriz Merchel Piovesan; Kim Minseung; Tagkopoulos Ilias; Schmitz Harold
    Frontiers in microbiology (2020), 11 (), 393 ISSN:1664-302X.
    Food and human health are inextricably linked. As such, revolutionary impacts on health have been derived from advances in the production and distribution of food relating to food safety and fortification with micronutrients. During the past two decades, it has become apparent that the human microbiome has the potential to modulate health, including in ways that may be related to diet and the composition of specific foods. Despite the excitement and potential surrounding this area, the complexity of the gut microbiome, the chemical composition of food, and their interplay in situ remains a daunting task to fully understand. However, recent advances in high-throughput sequencing, metabolomics profiling, compositional analysis of food, and the emergence of electronic health records provide new sources of data that can contribute to addressing this challenge. Computational science will play an essential role in this effort as it will provide the foundation to integrate these data layers and derive insights capable of revealing and understanding the complex interactions between diet, gut microbiome, and health. Here, we review the current knowledge on diet-health-gut microbiota, relevant data sources, bioinformatics tools, machine learning capabilities, as well as the intellectual property and legislative regulatory landscape. We provide guidance on employing machine learning and data analytics, identify gaps in current methods, and describe new scenarios to be unlocked in the next few years in the context of current knowledge.
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    Simmons, G.; Lee, F.; Kim, M.; Holt, R.; Tagkopoulos, I. Identification of Differential, Health-Related Compounds in Chardonnay Marc through Network-Based Meta-Analysis. Current Developments in Nutrition 2020, 4, 475,  DOI: 10.1093/cdn/nzaa045_108
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    Iuga, M.; Mironeasa, S. Potential of grape byproducts as functional ingredients in baked goods and pasta. Compr Rev. Food Sci. Food Safe 2020, 19 (5), 2473– 2505,  DOI: 10.1111/1541-4337.12597
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    Rainero, G.; Bianchi, F.; Rizzi, C.; Cervini, M.; Giuberti, G.; Simonato, B. Breadstick fortification with red grape pomace: effect on nutritional, technological and sensory properties. J. Sci. Food Agric 2022, 102 (6), 2545– 2552,  DOI: 10.1002/jsfa.11596
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    Breadstick fortification with red grape pomace: effect on nutritional, technological and sensory properties
    Rainero, Giada; Bianchi, Federico; Rizzi, Corrado; Cervini, Mariasole; Giuberti, Gianluca; Simonato, Barbara
    Journal of the Science of Food and Agriculture (2022), 102 (6), 2545-2552CODEN: JSFAAE; ISSN:0022-5142. (John Wiley & Sons Ltd.)
    Grape pomace (GP), a wine-making byproduct rich in dietary fiber (DF) and total phenolic compds. (TPC), is a potential functional ingredient in the fortification of baked goods. In the present study, fortified breadsticks samples were obtained by replacing wheat flour with 0, 5 and 10 g 100 g-1 of powd. GP (GPP). The GPP inclusion affected the rheol. properties of the doughs by increasing the water absorption and tenacity (P) at the same time as reducing the extensibility (L), with a significant increase in the P/L value and a decrease in the swelling index (G) value and deformation energy (W). Textural characteristics of breadsticks were influenced by the GPP addn., showing a redn. in hardness and fracturability as the amt. of GPP increased in the recipe. The GPP fortified breadsticks exhibited decreased pH, vol. and sp. vol. values compared to the control. The TPC and the antioxidant capacity increased in GPP fortified breadsticks, whereas the increased amt. of DF allowed the products to benefit from the claim 'high fiber content' at the highest level of GPP inclusion. The sensory evaluation revealed that GPP addn. increased wine odor, acidity, bitterness, astringency and hardness, and decreased the regularity of alveolation and friability. Finally, the GPP fortified products achieved good sensorial acceptability. GPP improved the nutritional values of fortified breadsticks and changed the rheol. of dough and breadsticks' technol. properties without affecting sensory acceptability. 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chem. Industry.
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    Šporin, M.; Avbelj, M.; Kovač, B.; Možina, S. S. Quality characteristics of wheat flour dough and bread containing grape pomace flour. Food Science and Technology International 2018, 24 (3), 251– 263,  DOI: 10.1177/1082013217745398
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    Quality characteristics of wheat flour dough and bread containing grape pomace flour
    Sporin, Monika; Avbelj, Martina; Kovac, Boris; Mozina, Sonja Smole
    Food Science and Technology International (London, United Kingdom) (2018), 24 (3), 251-263CODEN: FSTIFZ; ISSN:1082-0132. (Sage Publications Ltd.)
    Wheat bread was enriched with 6%, 10% and 15% dried and milled grape pomace flour from two grape cultivars: 'Merlot' and 'Zelen'. Rheol., textural, sensory and antioxidant properties of the enriched dough and bread were evaluated, and compared to control samples. Grape cultivar had significant impact on the rheol. characteristics of the dough, and on the sensory and antioxidant properties of the final bread. Development time and dough stability were longer when 'Merlot' grape pomace flour was added compared to 'Zelen' grape pomace flour and the control. Grape pomace flour addn. affected bread vol., firmness, crumb and crust color, and odor and taste intensity. Moreover, grape pomace flour addn. resulted in a stickier and less springy crumb texture, and some neg. sensorial properties, such as increased intensity of aftertaste and sand feeling in the mouth. The phenolic content and antioxidant activity of bread were pos. correlated with grape pomace flour addn. (r = 0.987, p = 0.01 and r = 0.941, p = 0.01 between phenolic content and ferric reducing antioxidant power and phenolic content and 2,2-diphenyl-1-picrylhydrazyl, resp.). The highest total phenolic contents were 5.92 mg gallic acid equiv. (GAE)/g dw for 'Merlot' and 3.65 mg gallic acid equiv. /g dw for 'Zelen', which were seen for the bread prepd. with the highest grape pomace flour addn. (15%). The highest antioxidant activity detd. by the 2,2-diphenyl-1-picrylhydrazyl and ferric reducing antioxidant power assays were seen for the bread prepd. with the highest 'Merlot' grape pomace flour addn. (15%). Dough characteristic and sensory profile are strongly influenced by cultivar of grape pomace flour. Based on results of sensory profiling, the variety 'Zelen' is suggested for use.
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    Gerardi, C.; D’amico, L.; Migoni, D.; Santino, A.; Salomone, A.; Carluccio, M. A.; Giovinazzo, G. Strategies for Reuse of Skins Separated From Grape Pomace as Ingredient of Functional Beverages. Front. Bioeng. Biotechnol. 2020, 8, 645,  DOI: 10.3389/fbioe.2020.00645
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    147
    Strategies for Reuse of Skins Separated From Grape Pomace as Ingredient of Functional Beverages
    Gerardi Carmela; D'amico Leone; Santino Angelo; Giovinazzo Giovanna; Migoni Danilo; Salomone Antonio; Carluccio Maria A
    Frontiers in bioengineering and biotechnology (2020), 8 (), 645 ISSN:2296-4185.
    Wine grape pomace, the by-product of wine making, is a source of polyphenols, metals, and organic acids, and may be exploited for the production of functional beverages. Among red wines, Primitivo and Negramaro varieties possess an interesting amount of polyphenolic compounds and other chemicals. Consequently, study of the biological activity of Primitivo and Negramaro vinification by-products is of great interest as well as optimizing the extraction of its bioactive components. In order to stabilize the grape pomace, different methods of drying grape pomace were tested. After stabilization of the pomace, the grape skins were manually separated from the seeds and any woody parts. The chemical characterizations of acidified alcoholic (methanol/ethanol) and water extracts and either microwave-assisted or ultrasound-assisted extractions of separated grape skins were compared. Besides that, the in vitro antioxidant activity of wine pomace skin extracts was also investigated as Trolox equivalents antioxidant capacity (TEAC) and oxygen radical absorbance capacity (ORAC). Overall, the alcoholic extractions were found to be the most effective for recovering phenolic compounds, when compared with those in water. Ultrasound- and microwave-assisted extraction of pomace skin using acidified water allowed the highest TEAC value. Taking into account the water extraction result, in order to reuse grape pomace skins to produce a functional beverage, we utilized them in combination with black tea, karkade (Hibiscus sabdariffa L.), or rooibos (Aspalathus linearis Burm.) to produce an infusion. The combination of grape skins and black tea showed the highest ratio of total phenol content to antioxidant activity. Moreover, skin isolated from pomace, with or without black tea infusions, were shown to have anti-inflammatory capacity in human cell culture. Our results raise the value of grape skin pomace as a rich source of bioactive compounds with antioxidant and anti-inflammatory activity and suggest its exploitation as an ingredient for functional beverages.
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    Tolve, R.; Simonato, B.; Rainero, G.; Bianchi, F.; Rizzi, C.; Cervini, M.; Giuberti, G. Wheat Bread Fortification by Grape Pomace Powder: Nutritional, Technological, Antioxidant, and Sensory Properties. Foods 2021, 10 (1), 75,  DOI: 10.3390/foods10010075
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    Wheat bread fortification by grape pomace powder: nutritional, technological, antioxidant, and sensory properties
    Tolve, Roberta; Simonato, Barbara; Rainero, Giada; Bianchi, Federico; Rizzi, Corrado; Cervini, Mariasole; Giuberti, Gianluca
    Foods (2021), 10 (1), 75CODEN: FOODBV; ISSN:2304-8158. (MDPI AG)
    Grape pomace powder (GPP), a byproduct from the winemaking process, was used to substitute flour for wheat bread fortification within 0, 5, and 10 g/100 g. Rheol. properties of control and fortified doughs, along with physicochem. and nutritional characteristics, antioxidant activity, and the sensory anal. of the obtained bread were considered. The GPP addn. influenced the doughs' rheol. properties by generating more tenacious and less extensible products. Concerning bread, pH values and vol. of fortified products decreased as the GPP inclusion level increased in the recipe. Total phenolic compds. and the antioxidant capacity of bread samples, evaluated by FRAP (ferric reducing ability of plasma) and ABTS (2,2''-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)) assays, increased with GPP addn. Moreover, the GPP inclusion level raised the total dietary fiber content of bread. Regarding sensory evaluation, GPP fortification had a major impact on the acidity, the global flavor, the astringency, and the wine smell of bread samples without affecting the overall bread acceptability. The current results suggest that GPP could be an attractive ingredient used to obtain fortified bread, as it is a source of fiber and polyphenols with potentially pos. effects on human health.
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    Kalušević, A.; Salević, A.; Jovanović, A.; Veljović, M.; Pravilović, R.; Nedović, V.; Trifković, K. Encapsulation of Plant Extracts. Encapsulation in Food Processing Fermentation 2022, 172,  DOI: 10.1201/9780429324918-7
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    Fischer, E.; Cayot, N.; Cachon, R. Potential of Microorganisms to Decrease the “Beany” Off-Flavor: A Review. J. Agric. Food Chem. 2022, 70 (15), 4493– 4508,  DOI: 10.1021/acs.jafc.1c07505
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    Potential of microorganisms to decrease the "Beany" off-flavor: A review
    Fischer, Estelle; Cayot, Nathalie; Cachon, Remy
    Journal of Agricultural and Food Chemistry (2022), 70 (15), 4493-4508CODEN: JAFCAU; ISSN:0021-8561. (American Chemical Society)
    A review. Vegetable proteins are in high demand due to current issues surrounding meat consumption and changes in eating habits, but they are still not accepted by consumers due to their strong bitterness, astringent taste, and "beany" off-flavor. This review aimed to give an overview of the "beany" off-flavor and the potential of microorganisms to decrease it. Twenty-six volatile compds. were identified from the literature as contributing to the "beany" off-flavor, and their formation pathways were identified in a legume matrix, pea. Biotechnol. ways to improve the flavor by reducing these volatile compds. were then looked over. As aldehydes and ketones are the main type of compds. directly linked to the "beany" off-flavor, alc. dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) were focused on. By converting aldehyde and ketones into alcs. or carboxylic acids, these two enzymes have the potential to decrease the off-flavor. The presence of the two enzymes in a selection of microorganisms (Lactobacillus acidophilus, Limosilactobacillus fermentum, Lactiplantibacillus plantarum, Streptococcus thermophilus, Saccharomyces cerevisiae, and Gluconobacter suboxydans) was done with a catabolism and a bioinformatical study. Finally, the correlation between the presence of the enzyme and the efficacy to improve the flavor was investigated by comparison with the literature. The presence of ADH and/or ALDH in the strain metab. seems linked to an odor improvement. Esp., a constitutive enzyme (ADH or ALDH) in the catabolism should give better results, showing that some fermentative types are more inclined to better the flavor. Obligatory fermentative strains, with a constitutive ADH, or acetic acid bacteria, with constitutive ADH and ALDH, show the best results and should be favored to reduce the amt. of compds. involved in the "beany" off-flavor and diminish that off-flavor in legume proteins.
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    Nature's Chemical Signatures in Human Olfaction: A Foodborne Perspective for Future Biotechnology
    Dunkel, Andreas; Steinhaus, Martin; Kotthoff, Matthias; Nowak, Bettina; Krautwurst, Dietmar; Schieberle, Peter; Hofmann, Thomas
    Angewandte Chemie, International Edition (2014), 53 (28), 7124-7143CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)
    A review. The biocatalytic prodn. of flavor naturals that det. chemosensory percepts of foods and beverages is an ever challenging target for academic and industrial research. Advances in chem. trace anal. and post-genomic progress at the chem.-biol. interface revealed odor qualities of nature's chemosensory entities to be defined by odorant-induced olfactory receptor activity patterns. Beyond traditional views, this review and meta-anal. now shows characteristic ratios of only about 3 to 40 genuine key odorants for each food, from a group of about 230 out of circa 10 000 food volatiles. This suggests the foodborn stimulus space has co-evolved with, and roughly match our circa 400 olfactory receptors as best natural agonists. This perspective gives insight into nature's chem. signatures of smell, provides the chem. odor codes of more than 220 food samples, and beyond addresses industrial implications for producing recombinants that fully reconstruct the natural odor signatures for use in flavors and fragrances, fully immersive interactive virtual environments, or humanoid bioelectronic noses.
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    Engel, W.; Bahr, W.; Schieberle, P. J. E. F. R. Technology, Solvent assisted flavour evaporation–a new and versatile technique for the careful and direct isolation of aroma compounds from complex food matrices. European Food Research Technology 1999, 209 (3), 237– 241,  DOI: 10.1007/s002170050486
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    154
    Solvent assisted flavor evaporation. A new and versatile technique for the careful and direct isolation of aroma compounds from complex food matrixes
    Engel, Wolfgang; Bahr, Wolfgang; Schieberle, Peter
    European Food Research and Technology (1999), 209 (3-4), 237-241CODEN: EFRTFO; ISSN:1438-2377. (Springer)
    A compact and versatile distn. unit was developed for the fast and careful isolation of volatiles from complex food matrixes. In connection with a high vacuum pump (5 × 10-3 Pa), the new technique, designated solvent assisted flavor evapn. (SAFE), allows the isolation of volatiles from either solvent exts., aq. foods, such as milk or beer, aq. food suspensions, such as fruit pulps, or even matrixes with a high oil content. Application of SAFE to model solns. of selected aroma compds. resulted in higher yields from both solvent exts. or fatty matrixes (50% fat) compared to previously used techniques, such as high vacuum transfer. Direct distn. of aq. fruit pulps in combination with a stable isotope diln. anal. enabled the fast quantification (60 min including MS anal.) of compds. such as the very polar and unstable 4-hydroxy-2,5-dimethyl-3(2H)-furanone in strawberries (3.2 mg/kg) and tomatoes (340 μg/kg). Furthermore, the direct distn. of aq. foods, such as beer or orange juice, gave flavorful aq. distillates free from non-volatile matrix compds.
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    Dein, M.; Moore, A.; Ricketts, C.; Huynh, C.; Munafo, J. P. Characterization of Odorants in Chardonnay Marc Skins. J. Agric. Food Chem. 2021, 69 (41), 12262– 12269,  DOI: 10.1021/acs.jafc.1c04195
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    155
    Characterization of Odorants in Chardonnay Marc Skins
    Dein, Melissa; Moore, Andrew; Ricketts, Casey; Huynh, Chelsea; Munafo Jr, John P.
    Journal of Agricultural and Food Chemistry (2021), 69 (41), 12262-12269CODEN: JAFCAU; ISSN:0021-8561. (American Chemical Society)
    Chardonnay marc, consisting of grape skins, seeds, and stems, is a coproduct of grape juice prodn. for Chardonnay wine making. The discovery that marc contains a rich source of health-promoting mols. has led to its growing popularity as a flavorful healthy food ingredient. However, the odorants responsible for its pleasant fruity aroma remain unknown. In this study, 35 odorants were identified in Chardonnay marc skins using solvent-assisted flavor evapn. (SAFE) and aroma ext. diln. anal. (AEDA). Thirteen odorants were quantitated employing stable isotope diln. assays (SIDAs), and odor activity values (OAVs) were calcd. Odorants with OAVs >1 included 3-methylnonane-2,4-dione (hay, OAV 5800), β-ionone (floral, violets, OAV 2900), (2E,4E)-nona-2,4-dienal (fatty, OAV 1200), β-damascenone (cooked apple, OAV 370), hexanal (green, OAV 260), oct-1-en-3-one (mushroom, OAV 200), linalool (floral, citrus, OAV 61), (2E,4E)-deca-2,4-dienal (fatty, OAV 60), 2-phenylethanol (floral, rose, OAV 16), 3-(methylsulfanyl)propanal (potato, OAV 3.7), HDMF (caramel, OAV 2.0), and Et octanoate (fruity, OAV 1.1). An odor simulation model prepd. using odorants with OAVs >1 sensorially matched the aroma of the Chardonnay marc skins. This investigation establishes a foundation for future studies aimed at detg. the contribution of individual Chardonnay marc components (skins, seeds, and stems) to the aroma profile of Chardonnay marc powder and aiding producers in delivering optimal and consistent aroma profiles by region.
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    Warner, S.; Munafo, J. Identification of odorants in chardonnay marc seeds; Presented at the American Chemical Society Meeting, San Diego, CA, USA, 2022; A165 3:53.
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    Scharbert, S.; Holzmann, N.; Hofmann, T. Identification of the Astringent Taste Compounds in Black Tea Infusions by Combining Instrumental Analysis and Human Bioresponse. J. Agric. Food Chem. 2004, 52 (11), 3498– 3508,  DOI: 10.1021/jf049802u
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    157
    Identification of the Astringent Taste Compounds in Black Tea Infusions by Combining Instrumental Analysis and Human BioresponseD
    Scharbert, Susanne; Holzmann, Nadine; Hofmann, Thomas
    Journal of Agricultural and Food Chemistry (2004), 52 (11), 3498-3508CODEN: JAFCAU; ISSN:0021-8561. (American Chemical Society)
    Application of taste diln. analyses on freshly prepd. black tea infusions revealed neither the high mol. wt. thearubigen-like polyphenols nor the catechins and theaflavins, but a series of 14 flavon-3-ol glycosides as the main contributors to the astringent taste perceived upon black tea consumption. Among these glycosides, the apigenin-8-C-[α-L-rhamnopyranosyl-(1→2)-O-β-D-glucopyranoside] was identified for the first time in tea infusions. Depending on the structure, the flavon-3-ol glycosides were found to induce a velvety and mouth-coating sensation at very low threshold concns., which were far below those of catechins or theaflavins; for example, the threshold of 0.001 μmol/L found for quercetin-3-O-[α-L-rhamnopyranosyl-(1→6)-O-β-D-glucopyranoside] is 190,000, or 16,000 times below the threshold detd. for epigallocatechin gallate or theaflavin, resp. Moreover, structure/activity considerations revealed that, besides the type of flavon-3-ol aglycon, the type and the sequence of the individual monosaccharides in the glycosidic chain are key drivers for astringency perception of flavon-3-ol glycosides.
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  158. 158
    Rotzoll, N.; Dunkel, A.; Hofmann, T. Activity-Guided Identification of (S)-Malic Acid 1-O-d-Glucopyranoside (Morelid) and γ-Aminobutyric Acid as Contributors to Umami Taste and Mouth-Drying Oral Sensation of Morel Mushrooms (Morchella deliciosa Fr.). J. Agric. Food Chem. 2005, 53 (10), 4149– 4156,  DOI: 10.1021/jf050056i
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    158
    Activity-Guided Identification of (S)-Malic Acid 1-O-D-Glucopyranoside (Morelid) and γ-Aminobutyric Acid as Contributors to Umami Taste and Mouth-Drying Oral Sensation of Morel Mushrooms (Morchella deliciosa Fr.)
    Rotzoll, Nina; Dunkel, Andreas; Hofmann, Thomas
    Journal of Agricultural and Food Chemistry (2005), 53 (10), 4149-4156CODEN: JAFCAU; ISSN:0021-8561. (American Chemical Society)
    Taste activity-guided fractionation of an aq. morel ext. by means of the recently developed taste diln. anal. (TDA) enabled the localization of several umami-like-tasting fractions as well as a fraction imparting an intense mouth-drying sensation to the oral cavity. Hydrophilic interaction liq. chromatog. (HILIC), LC-MS, and amino acid anal. led to the successful identification of γ-aminobutyric acid as the chem. inducer of the mouth-drying and mouth-coating oral sensations imparted by the morel ext. Besides the well-known umami-like taste contributors L-glutamic acid, L-aspartic acid, and succinic acid, an addnl. HILIC fraction was isolated and evaluated as tasting umami-like. LC-MS and NMR studies revealed that this fraction consisted of a mixt. of (S)-malic acid 1-O-α-D-glucopyranoside and (S)-malic acid 1-O-β-D-glucopyranoside, the structure of which could be successfully confirmed by independent synthesis. To the best of our knowledge, this morel-derived glycoside, named (S)-morelid, has previously not been reported in any food products. Sensory anal. of aq. solns. of the compds. identified revealed threshold concns. of 0.02 mmol/L for the mouth-drying effect of γ-aminobutyric acid and 6.0 mmol/L for the umami-like, slightly sour taste of (S)-morelid.
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    Hufnagel, J. C.; Hofmann, T. Orosensory-Directed Identification of Astringent Mouthfeel and Bitter-Tasting Compounds in Red Wine. J. Agric. Food Chem. 2008, 56 (4), 1376– 1386,  DOI: 10.1021/jf073031n
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    159
    Orosensory-Directed Identification of Astringent Mouthfeel and Bitter-Tasting Compounds in Red Wine
    Hufnagel, Jan Carlos; Hofmann, Thomas
    Journal of Agricultural and Food Chemistry (2008), 56 (4), 1376-1386CODEN: JAFCAU; ISSN:0021-8561. (American Chemical Society)
    Application of sequential solvent extn., followed by HPLC combined with the taste diln. anal., enabled the localization of the most intense velvety astringent, drying, and puckering astringent, as well as bitter-tasting, compds. in red wine, resp. Isolation of the taste components involving gel adsorption chromatog., ultrafiltration, and synthesis revealed the identification of 26 sensory-active nonvolatiles, among which several hydroxybenzoic acids, hydroxycinnamic acids, flavon-3-ol glycosides, and dihydroflavon-3-ol rhamnosides as well as a structurally undefined polymeric fraction (>5 kDa) were identified as the key astringent components. In contradiction to literature suggestions, flavan-3-ols were found to be not of major importance for astringency and bitter taste, resp. Surprisingly, a series of hydroxybenzoic acid Et esters and hydroxycinnamic acid Et esters were identified as bitter compds. in wine. Taste qualities and taste threshold concns. of the individual wine components were detd. by means of a 3-alternative forced-choice test and the half-mouth test, resp.
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    Warmke, R.; Belitz, H. D.; Grosch, W. Evaluation of taste compounds of Swiss cheese (Emmentaler). Zeitschrift für Lebensmittel-Untersuchung und Forschung 1996, 203 (3), 230– 235,  DOI: 10.1007/BF01192869
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    Evaluation of taste compounds of Swiss cheese (Emmentaler)
    Warmke, Rainer; Belitz, Hans Dieter; Grosch, Werner
    Zeitschrift fuer Lebensmittel-Untersuchung und -Forschung (1996), 203 (3), 230-235CODEN: ZLUFAR; ISSN:0044-3026. (Springer)
    The following substances were evaluated as potent taste compds.: acetic acid, propionic acid, lactic acid, succinic acid and glutamic acid, each in free form and/or as ammonium, sodium, potassium, magnesium and calcium salts, as well as the corresponding chlorides and phosphates. Magnesium and calcium propionate mainly caused the sweetish note in the taste profile of Emmentaler. Although bitter tasting amino acids and peptides occurred in the cheese sample, they were not detected in the taste profile.
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    Toelstede, S.; Hofmann, T. Sensomics Mapping and Identification of the Key Bitter Metabolites in Gouda Cheese. J. Agric. Food Chem. 2008, 56 (8), 2795– 2804,  DOI: 10.1021/jf7036533
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    Sensomics mapping and identification of the key bitter metabolites in Gouda cheese
    Toelstede, Simone; Hofmann, Thomas
    Journal of Agricultural and Food Chemistry (2008), 56 (8), 2795-2804CODEN: JAFCAU; ISSN:0021-8561. (American Chemical Society)
    Application of a sensomics approach on the water-sol. ext. of a matured Gouda cheese including gel permeation chromatog., ultrafiltration, solid phase extn., preparative RP-HPLC, and HILIC combined with anal. sensory tools enabled the comprehensive mapping of bitter-tasting metabolites. LC-MS-TOF and LC-MS/MS, independent synthesis, and sensory anal. revealed the identification of a total of 16 bitter peptides formed by proteolysis of caseins. Eleven previously unreported bitter peptides were aligned to β-casein, among which 6 peptides were released from the sequence β-CN(57-69) of the N terminus of β-casein and 2 peptides originated from the C-terminal sequence β-CN(198-206). The other peptides were liberated from misc. regions of β-casein, namely, β-CN(22-28), β-CN(74-86), β-CN(74-77), and β-CN(135-138), resp. Six peptides were found to originate from αs1-casein and were shown to have the sequences αs1-CN(11-14), αs1-CN(56-60), αs1-CN(70/71-74), αs1-CN(110/111-114), and αs1-CN(135-136). Sensory evaluation of the purified, synthesized peptides revealed that 12 of these peptides showed pronounced bitter taste with recognition thresholds between 0.05 and 6.0 mmol/L. Among these peptides, the decapeptide YPFPGPIHNS exhibited a caffeine-like bitter taste quality at the lowest threshold concn. of 0.05 mmol/L.
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    Hayashi, T.; Yamaguchi, K.; Konosu, S. Sensory Analysis of Taste-Active Components in the Extract of Boiled Snow Crab Meat. J. Food Sci. 1981, 46 (2), 479– 483,  DOI: 10.1111/j.1365-2621.1981.tb04890.x
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    162
    Sensory analysis of taste-active components in the extract of boiled snow crab meat
    Hayashi, T.; Yamaguchi, K.; Konosu, S.
    Journal of Food Science (1981), 46 (2), 479-83, 493CODEN: JFDSAZ; ISSN:0022-1147.
    A synthetic ext., prepd. from 44 compds. on the basis of the anal. data on the leg meat ext. of the boiled snow crab (Chionoecetes opilio), satisfactorily reproduced the taste of the natural ext. except for a slight lack of body and mildness. A series of taste panel assessments on synthetic exts. prepd. by omitting or adding extractive component(s) were carried out by a triangle difference test and changes in taste profile were assessed. Only 12 components, alanine [56-41-7], arginine [74-79-3], glutamic acid [56-86-0], glycine [56-40-6], glycine betaine [107-43-7], AMP [61-19-8], CMP [63-37-6], GMP [85-32-5], Na+, K+, Cl-, and PO43-, were found to contribute more or less toward producing the characteristic taste of the snow crab.
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    Petrisor, C.; Chireceanu, C. Organic acids and sugars profile of some grape cultivars affected by grapevine yellows symptoms. Romanian Biotechnology Letter 2019, 24, 1027– 1033,  DOI: 10.25083/rbl/24.6/1027.1033
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    163
    Organic acids and sugars profile of some grape cultivars affected by grapevine yellows symptoms
    Petrisor, Cristina; Chireceanu, Constantina
    Romanian Biotechnological Letters (2019), 24 (6), 1027-1033CODEN: RBLEFU; ISSN:1224-5984. (Ars Docendi)
    Grapevine yellows are a group of infectious diseases, which are usually assocd. with phytoplasma pathogens, affecting quality of grapes and survival of grapevine. The objective of this work was to evaluate sugars, total phenols and org. acids concns. in the grapes of four wine cultivars (Feteasca Neagra, Pinot Noir, Traminer rose, Chardonnay) healthy and affected by specific symptoms to phytoplasmoses. Berry samples were collected from the Minis-Maderat (Arad County) and Odobesti (Vrancea County) vineyards. Individual sugars and org. acids compds. were identified and quantified in grape berries by the high performance liq. chromatog. (HPLC) method using DAD and RID detectors, while total phenolic compds. by using spectrophotometry. The content and compn. of sugars and acids varied between healthy and symptomatic plants. Anal. of grape juice revealed redn. in sugars (fructose and glucose) from symptomatic to non-symptomatic vines. Lower values of acidity were obtained in grapes of affected compared to non-affected vines. The differences in acids content between grapes of affected and not affected vines were more pronounced at Pinot Noir variety, with lower concns. of malic and tartaric acids in grapes from symptomatic vines in both locations studied. The affected grapes did not differ significantly from the healthy ones, regarding to succinic acid content. A notable increase of total phenolic compds. was obsd. in symptomatic compared to asymptomatic grape berries. The results of this paper showed a clear neg. effect of the phytoplasmoses symptoms on grape fruits compn.
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    Gao, Y.; Li, X. X.; Han, M. M.; Yang, X. F.; Li, Z.; Wang, J.; Pan, Q. H. Rain-Shelter Cultivation Modifies Carbon Allocation in the Polyphenolic and Volatile Metabolism of Vitis vinifera L. Chardonnay Grapes. PLoS One 2016, 11 (5), e0156117  DOI: 10.1371/journal.pone.0156117
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    164
    Rain-shelter cultivation modifies carbon allocation in the polyphenolic and volatile metabolism of vitis vinifera l. chardonnay Grapes
    Gao, Yuan; Li, Xiao-Xi; Han, Mei-Mei; Yang, Xiao-Fan; Li, Zheng; Wang, Jun; Pan, Qiu-Hong
    PLoS One (2016), 11 (5), e0156117/1-e0156117/27CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)
    This study investigated the effect of rain-shelter cultivation on the biosynthesis of flavonoids and volatiles in grapes, with an aim of detg. whether rain-shelter application could help to improve the sensory attributes and quality of grapes. Vitis vinifera L. Chardonnay grapes, grown in the Huaizhuo basin region of northern China, were selected within two consecutive years. A rain-shelter roof was constructed using a colorless polyethylene (PE) film with a light transmittance of 80%. Results showed that rain-shelter treatment did not affect the accumulation of sol. solids during grape maturation. However, the allocation of assimilated carbon in phenolic and volatile biosynthetic pathways varied significantly, leading to alterations in polyphenolic and volatile profiles. The rain-shelter cultivation enhanced the concn. of flavan-3-ols via the flavonoid-3'5'-hydroxylase (F3'5'H) pathway, but reduced the level of flavonols and flavan-3-ols via the flavonoid-3'-hydroxylase (F3'H) pathway. In addn., the rain-shelter cultivation significantly enhanced the synthesis of fatty acid-derived volatiles, isoprene-derived terpenoids and amino acid-derived branched-chain aliphatics, but led to a decrease in the accumulation of isoprene-derived norisoprenoids and amino acid-derived benzenoids. Principal component anal. revealed some key compds. that differentiated the grapes cultivated under open-field and rainshelter conditions. Moreover, the effect of the rain-shelter application on the accumulation of these compds. appeared to be vintage dependent. The alteration of their profiles caused by the rain-shelter treatment was significant in the vintage that received higher rainfall, which usually took place in the first rapid growth and veraison phases.
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    Rusjan, D.; Veberic, R.; Mikulic-Petkovsek, M. The response of phenolic compounds in grapes of the variety ’Chardonnay’ (Vitis vinifera L.) to the infection by phytoplasma Bois noir. Eur. J. Plant Pathol 2012, 133 (4), 965– 974,  DOI: 10.1007/s10658-012-9967-7
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    165
    The response of phenolic compounds in grapes of the variety 'Chardonnay' (Vitis vinifera L.) to the infection by phytoplasma Bois noir
    Rusjan, Denis; Veberic, Robert; Mikulic-Petkovsek, Maja
    European Journal of Plant Pathology (2012), 133 (4), 965-974CODEN: EPLPEH; ISSN:0929-1873. (Springer)
    The study was carried out on phytoplasma susceptible grapevine variety 'Chardonnay' (Vitis vinifera L.). The changes in total and individual phenolics, with a focus on hydroxycinnamic acids, flavanols and flavonol contents, were studied in phytoplasma-symptomatic and non-symptomatic berries of Bois noir (BN) infected and uninfected vines. Evident responses to BN infection at veraison have been monitored in a decreased accumulation of caftaric and coutaric acids, p-coumaroyl hexose, procyanidin B1, procyanidin trimer as well as of quercetin-3-O-glucoside, quercetin-3-O-glucuronide and quercetin-3-O-xyloside. At berry softening BN infection statistically increased the content of total phenolics, hydroxycinnamic acids and flavanols, but decreased the flavonol contents, esp. at phytoplasma-symptomatic berry skins. Later, at harvest, the BN infection caused an addnl. significant decrease of coutaric acid and p-coumaroyl pentose contents, moreover of procyanidin B1 and procyanidin dimmers (1, 2, and 3), trimer, kaempferol-3-O-glucoside and of most identified quercetins, except of quercetin-3-O-xyloside. At harvest, non-symptomatic berries from infected plants showed similar dynamics in the total phenolic content compared to berry skins from uninfected plants, but in total flavanols and flavonols content similarity to those symptomatic was obsd. The latter decreases grape quality and its antioxidant potential. The Bois noir disease showed specific, local and growth-phase-induced responses regarding the content of phenolics in berry skins, where in particular the differences between phytoplasma-symptomatic and non-symptomatic grapes have to be underlined.
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    Garcia-Jares, C.; Vazquez, A.; Lamas, J. P.; Pajaro, M.; Alvarez-Casas, M.; Lores, M. Antioxidant White Grape Seed Phenolics: Pressurized Liquid Extracts from Different Varieties. Antioxidants 2015, 4 (4), 737– 749,  DOI: 10.3390/antiox4040737
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    166
    Antioxidant white grape seed phenolics: pressurized liquid extracts from different varieties
    Garcia-Jares, Carmen; Vazquez, Alberto; Lamas, Juan P.; Pajaro, Marta; Alvarez-Casas, Marta; Lores, Marta
    Antioxidants (2015), 4 (4), 737-749CODEN: ANTIGE; ISSN:2076-3921. (MDPI AG)
    Grape seeds represent a high percentage (20% to 26%) of the grape marc obtained as a byproduct from white winemaking and keep a vast proportion of grape polyphenols. In this study, seeds obtained from 11 monovarietal white grape marcs cultivated in Northwestern Spain have been analyzed in order to characterize their polyphenolic content and antioxidant activity. Seeds of native (Albari~no, Cai~no, Godello, Loureiro, Torront´es, and Treixadura) and non-native (Chardonnay, Gewurtztr.ovrddot.aminer, Pinot blanc, Pinot gris, and Riesling) grape varieties have been considered. Low wt. phenolics have been extd. by means of pressurized liq. extn. (PLE) and further analyzed by LC-MS/MS. The results showed that PLE exts., whatever the grape variety of origin, contained large amts. of polyphenols and high antioxidant activity. Differences in the varietal polyphenolic profiles were found, so a selective exploitation of seeds might be possible.
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    Pantelić, M. M.; Dabić Zagorac, D. Č.; Davidović, S. M.; Todić, S. R.; Bešlić, Z. S.; Gašić, U. M.; Tešić, Ž. L.; Natić, M. M. Identification and quantification of phenolic compounds in berry skin, pulp, and seeds in 13 grapevine varieties grown in Serbia. Food Chem. 2016, 211, 243– 252,  DOI: 10.1016/j.foodchem.2016.05.051
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    167
    Identification and quantification of phenolic compounds in berry skin, pulp, and seeds in 13 grapevine varieties grown in Serbia
    Pantelic, Milica M.; Dabic Zagorac, Dragana C.; Davidovic, Sonja M.; Todic, Slavica R.; Beslic, Zoran S.; Gasic, Ur