A Systematic Review and Comprehensive Evaluation of Human Intervention Studies to Unravel the Bioavailability of Hydroxycinnamic Acids.

Significance: Hydroxycinnamic acids (HCAs) are the main phenolic acids in the western diet. Harmonizing the available information on the absorption, distribution, metabolism, and excretion (ADME) of HCAs is fundamental to unraveling the compounds responsible for their health effects. This work systematically assessed pharmacokinetics, including urinary recovery, and bioavailability of HCAs and their metabolites, based on literature reports. Recent Advances: Forty-seven intervention studies with coffee, berries, herbs, cereals, tomato, orange, grape products, and pure compounds, as well as other sources yielding HCA metabolites, were included. Up to 105 HCA metabolites were collected, mainly acyl-quinic and C6-C3 cinnamic acids. C6-C3 cinnamic acids, such as caffeic and ferulic acid, reached the highest blood concentrations (maximum plasma concentration [Cmax] = 423 nM), with time to reach Cmax (Tmax) values ranging from 2.7 to 4.2 h. These compounds were excreted in urine in higher amounts than their phenylpropanoic acid derivatives (4% and 1% of intake, respectively), but both in a lower percentage than hydroxybenzene catabolites (11%). Data accounted for 16 and 18 main urinary and blood HCA metabolites, which were moderately bioavailable in humans (collectively 25%). Critical Issues: A relevant variability emerged. It was not possible to unequivocally assess the bioavailability of HCAs from each ingested source, and data from some plant based-foods were absent or inconsistent. Future Directions: A comprehensive study investigating the ADME of HCAs derived from their most important dietary sources is urgently required. Eight key metabolites were identified and reached interesting plasma Cmax concentrations and urinary recoveries, opening up new perspectives to evaluate their bioactivity at physiological concentrations. Antioxid. Redox Signal. 40, 510-541.

Effect of the Pasta Making Process on Slowly Digestible Starch Content.

The rate at which starch is digested in the human intestine elicits different glycemic responses and reflects the glycemic index (GI) of foods. In vitro measurement of starch digestibility can reflect the GI of food. Differences in starch digestibility among four durum wheat pasta samples, couscous, and bread were evaluated to better describe the role of the pasta making process in affecting starch digestibility. Statistical differences in RDS (rapidly digestible starch), SDS (slowly digestible starch), and RS (resistant starch) of products were found (p < 0.05). As expected, pasta samples showed the highest value of SDS/av starch compared to couscous and bread. Fusilli and cavatelli samples presented the highest SDS/av starch ratio (55.80 ± 3.06% and 53.91 ± 3.50%, respectively), then came spaghetti 49.39 ± 2.83% and penne 45.93 ± 1.19%, while couscous presented the lowest value of SDS/av starch (2.64 ± 0.50%), followed by bread (11.78 ± 2.63%). Our study confirmed that the pasta making process efficiently mediates an increase in SDS/Av starch content, which has been specifically quantified above 40%, therefore strongly related to a lowered glycemic response in vivo. Our results strengthened the concept that pasta is a good source of SDS, which makes it useful for glycemic control.

Systematic Review on the Metabolic Interest of Glucosinolates and Their Bioactive Derivatives for Human Health.

In the last decade, most of the evidence on the clinical benefits of including cruciferous foods in the diet has been focused on the content of glucosinolates (GSL) and their corresponding isothiocyanates (ITC), and mercapturic acid pathway metabolites, based on their capacity to modulate clinical, biochemical, and molecular parameters. The present systematic review summarizes findings of human studies regarding the metabolism and bioavailability of GSL and ITC, providing a comprehensive analysis that will help guide future research studies and facilitate the consultation of the latest advances in this booming and less profusely researched area of GSL for food and health. The literature search was carried out in Scopus, PubMed and the Web of Science, under the criteria of including publications centered on human subjects and the use of Brassicaceae foods in different formulations (including extracts, beverages, and tablets), as significant sources of bioactive compounds, in different types of subjects, and against certain diseases. Twenty-eight human intervention studies met inclusion criteria, which were classified into three groups depending on the dietary source. This review summarizes recent studies that provided interesting contributions, but also uncovered the many potential venues for future research on the benefits of consuming cruciferous foods in our health and well-being. The research will continue to support the inclusion of GSL-rich foods and products for multiple preventive and active programs in nutrition and well-being.

Revisiting the bioavailability of flavan-3-ols in humans: A systematic review and comprehensive data analysis.

This systematic review summarizes findings from human studies investigating the different routes of absorption, metabolism, distribution and excretion (ADME) of dietary flavan-3-ols and their circulating metabolites in healthy subjects. Literature searches were performed in PubMed, Scopus and the Web of Science. Human intervention studies using single and/or multiple intake of flavan-3-ols from food, extracts, and pure compounds were included. Forty-nine human intervention studies met inclusion criteria. Up to 180 metabolites were quantified from blood and urine samples following intake of flavan-3-ols, mainly as phase 2 conjugates of microbial catabolites (n = 97), with phenyl-γ-valerolactones being the most representative ones (n = 34). Phase 2 conjugates of monomers and phenyl-γ-valerolactones, the main compounds in both plasma and urine, reached two peak plasma concentrations (Cmax) of 260 and 88 nmol/L at 1.8 and 5.3 h (Tmax) after flavan-3-ol intake. They contributed to the bioavailability of flavan-3-ols for over 20%. Mean bioavailability for flavan-3-ols was moderate (31 ± 23%, n bioavailability values = 20), and it seems to be scarcely affected by the amount of ingested compounds. While intra- and inter-source differences in flavan-3-ol bioavailability emerged, mean flavan-3-ol bioavailability was 82% (n = 1) and 63% (n = 2) after (-)-epicatechin and nut (hazelnuts, almonds) intake, respectively, followed by 25% after consumption of tea (n = 7), cocoa (n = 5), apples (n = 3) and grape (n = 2). This highlights the need to better clarify the metabolic yield with which monomer flavan-3-ols and proanthocyanidins are metabolized in humans. This work clarified in a comprehensive way for the first time the ADME of a (poly)phenol family, highlighting the pool of circulating compounds that might be determinants of the putative beneficial effects linked to flavan-3-ol intake. Lastly, methodological inputs for implementing well-designed human and experimental model studies were provided.

Human colonic catabolism of dietary flavan-3-ol bioactives.

Understanding the fate of ingested polyphenols is crucial in elucidating the molecular mechanisms underlying the beneficial effects of a fruit and vegetable-based diet. This review focuses on the colon microbiota-mediated transformation of the flavan-3-ols and the structurally related procyanidins found in dietary plant foods and beverages, plus the flavan-3-ol-derived theaflavins of black tea, and the post-absorption phase II metabolism of the gut microbiota catabolites. Despite significant advances in the last decade major analytical challenges remain. Strategies to address them are presented.

In Vitro Colonic Fermentation of (Poly)phenols and Organosulfur Compounds of Fresh and Black Garlic.

The beneficial properties associated with garlic consumption have been related to the presence of bioactive compounds including (poly)phenols and organosulfur compounds (OSCs). This study aims to assess the effect of in vitro colonic fermentation on fresh and black garlic by determining the transformation of these compounds through ultrahigh-performance liquid chromatography coupled to mass spectrometry with a linear ion trap (uHPLC-LIT-MS). Colonic fermentation had a similar influence on the phenolic content of fresh and black garlic, with total respective decreases of 43.8% and 41.7%. Meanwhile, fermentation resulted in a significant decrease (33%) in OSCs in black garlic. Compounds such as 4-hydroxybenzoic acid, S-allylcysteine (SAC), and methionine sulfoxide were the phenolic compounds and OSCs with the highest concentration in fresh and black garlic after the in vitro fermentation. These compounds, potentially present at the colonic level, might be responsible for the systemic health benefits associated with the consumption of black and fresh garlic.

Effects of colonic fermentation on the stability of fresh and black onion bioactives.

The health properties related to onion intake are attributed mainly to the presence of bioactive compounds, particularly phenolic and organosulfur compounds (OSCs). The aim of this study was to investigate, for the first time, the effect of an in vitro colonic fermentation on the stability of phenolic and OSCs of fresh and black onion by ultra-high-performance liquid chromatography coupled with mass spectrometry with a linear ion trap (UHPLC-LIT-MS). Throughout colonic fermentation, fresh onion showed an increase in the total phenolic content of 45%, mainly due to an increase in the content of the flavonoid family, while the OSCs remained stable along the fermentation. Black onion presented a different behaviour, showing significant decreases in total (poly)phenol and OSC content, 22 and 48%, respectively. The main compounds found after the in vitro colonic fermentation of fresh onion were isorhamnetin (141 µmol L-1), quercetin (95 µmol L-1), 3,4-dihydroxybenzoic acid (53 µmol L-1), methionine sulfoxide (100 µmol L-1) and S-allylcysteine (SAC) (21.7 µmol L-1), whereas 3,4-dihydroxybenzoic acid (70 µmol L-1), 4-hydroxyphenylacetic acid (68 µmol L-1), methionine sulfoxide (82 µmol L-1) and S-propylmercapto-L-cysteine (SPMC) (10.1 µmol L-1) accounted for the highest concentrations of phenolics and OSCs in fermented black onion. These compounds, presumably present for their absorption and action at the colonic level, could be related to the health benefits of regular consumption of fresh and black onion.

Evolutionary Wheat Populations in High-Quality Breadmaking as a Tool to Preserve Agri-Food Biodiversity.

Plant biodiversity preservation is one of the most important priorities of today's agriculture. Wheat (Triticum spp. L.) is widely cultivated worldwide, mostly under a conventional and monovarietal farming method, leading to progressive biodiversity erosion. On the contrary, the evolutionary population (EP) cultivation technique is characterized by mixing and sowing together as many wheat genotypes as possible to allow the crop to genetically adapt over the years in relation to specific pedoclimatic conditions. The objective of this study was to assess the nutritional, chemical and sensory qualities of three different breads obtained using different organic EP flours, produced following a traditional sourdough process and compared to a commercial wheat cultivar bread. Technological parameters, B-complex vitamins, microelements, dietary fibre and phenolic acids were determined in raw materials and final products. Flours obtained by EPs showed similar characteristics to the commercial wheat cultivar flour. However, significant differences on grain technological quality were found. The breads were comparable with respect to chemical and nutritional qualities. Overall, the sensory panellists rated the tasted breads positively assigning the highest score to those produced with EPs flours (6.75-7.02) as compared to commercial wheat cultivar-produced bread (cv. Bologna, 6.36).

In Vitro Faecal Fermentation of Monomeric and Oligomeric Flavan-3-ols: Catabolic Pathways and Stoichiometry.

SCOPE: The study evaluates the influence of flavan-3-ol structure on the production of phenolic catabolites, principally phenyl-γ-valerolactones (PVLs), and phenylvaleric acids (PVAs). METHODS AND RESULTS: A set of 12 monomeric flavan-3-ols and proanthocyanidins (degree of polymerization (DP) of 2-5), are fermented in vitro for 24 h using human faecal microbiota, and catabolism is analyzed by UHPLC-ESI-MS/MS. Up to 32 catabolites strictly related to microbial catabolism of parent compounds are detected. (+)-Catechin and (-)-epicatechin have the highest molar mass recoveries, expressed as a percentage with respect to the incubated concentration (75 µmol L-1 ) of the parent compound, for total PVLs and PVAs, both at 5 h (about 20%) and 24 h (about 40%) of faecal incubation. Only A-type dimer and B-type procyanidins underwent the ring fission step, and no differences are found in total PVL and PVA production (≃1.5% and 6.0% at 5 and 24 h faecal incubation, respectively) despite the different DPs. CONCLUSION: The flavan-3-ol structure strongly affects the colonic catabolism of the native compounds, influencing the profile of PVLs and PVAs produced in vitro. This study opens new perspectives to further elucidate the colonic fate of oligomeric flavan-3-ols and their availability in producing bioactive catabolites.

Glycemic Index Values of Pasta Products: An Overview.

Durum wheat pasta is considered a low-glycemic index (GI) food. In recent years, the interest in developing enriched pasta has increased. Since both the formulation and processing technologies may affect the GI, this study aimed to investigate the GI values of pasta products (pp) reported in the literature until 2020. GI values of pp analyzed following the ISO guidelines were included in this survey. A total of 95 pp were identified and, according to their formulation, classified into 10 categories (n, mean GI): category n 1: 100% refined wheat (35, 55); category n 2: 100% whole wheat (6, 52); category n 3: other cereal-based products (8, 52); category n 4: containing egg (5, 52); category n 5: gluten free (11, 60); category n 6: containing legumes (9, 46); category n 7: noodles and vermicelli (9, 56); category n 8: containing vegetable or algae (6, 51); category n 9: containing other ingredients (5, 37); category n 10: stuffed (1, 58). Overall, pasta is confirmed to be a medium-low-GI food, even if a high variability among or within each category emerged. The formulation of enriched pp able to elicit a controlled glycemic response could represent a strategy to improve the nutritional value of pasta.

In vitro (poly)phenol catabolism of unformulated- and phytosome-formulated cranberry (Vaccinium macrocarpon) extracts.

Cranberries (Vaccinium macrocarpon) represent an important source of anthocyanins, flavan-3-ols and flavonols. This study aimed at investigating in vitro the human microbial metabolism of (poly)phenols, principally flavan-3-ols, of unformulated- and phytosome-formulated cranberry extracts. After powder characterization, a 24-h fermentation with human faecal slurries was performed, standardizing the concentration of incubated proanthocyanidins. Cranberry (poly)phenol metabolites were quantified by uHPLC-MS2 analyses. The native compounds of both unformulated- and phytosome-formulated cranberry extracts were metabolized under faecal microbiota activity, resulting in twenty-four microbial metabolites. Although some differences appeared when considering different classes of colonic metabolites, no significant differences in the total amount of metabolites were established after 24 h of incubation period. These results suggested that a different formulation had no effect on flavan-3-ol colonic metabolism of cranberry and both unformulated- and phytosome-formulated extract. Both formulations displayed the capability to be a potential source of compounds which could lead to a wide array of gut microbiota metabolites in vitro.

The importance of glycemic index on post-prandial glycaemia in the context of mixed meals: A randomized controlled trial on pasta and rice.

BACKGROUND AND AIMS: Post-prandial glycemic response (PPGR) depends on the intrinsic characteristic of the carbohydrate-rich foods as well as on the amount and type of other nutrients. This study aimed to explore whether the addition of condiments can affect the difference in PPGR between a low and a medium-high Glycemic Index (GI) food. METHODS AND RESULTS: Spaghetti (S) and rice ® were consumed plain and after adding tomato sauce and extra virgin olive oil (TEVOO), or pesto sauce (P). The GI of R (63 ± 3) was statistically higher than that of S (44 ± 7) (p = 0.003). The Incremental Area Under the Curve (IAUC) for R was significantly greater than S (124.2 ± 12.1 and 82.1 ± 12.9 mmol∗min/L respectively) (p = 0.016) for blood glucose but not for insulin (1192.6 ± 183.6 and 905.2 ± 208.9 mU∗min/L, respectively) (p = 0.076). There were no significant differences after the addition of either TEVOO or P. The postprandial peaks of blood glucose and insulin for R (6.7 ± 0.3 mmol/L and 36.4 ± 4.9 mU/L, respectively) were significantly higher compared to S (6.0 ± 0.2 mmol/L and 26.7 ± 3.6 mU/L, respectively) (p = 0.033 and p = 0.025). The postprandial peak for insulin remained significantly higher with P (36.8 ± 3.7 and 28.6 ± 2.9 mU/L for R + P and S + P, p = 0.045) but not with EVOO (p = 0.963). Postprandial peaks for blood glucose were not significantly different with condiment. CONCLUSIONS: The differences in PPGR were significant between spaghetti and rice consumed plain, they reduced or disappeared with fat adding, depending on the type of condiment used. REGISTRATION NUMBER: (www.clinicaltrial.gov):NCT03104712.

The Human Microbial Metabolism of Quercetin in Different Formulations: An In Vitro Evaluation.

Quercetin is one of the main dietary flavonols, but its beneficial properties in disease prevention may be limited due to its scarce bioavailability. For this purpose, delivery systems have been designed to enhance both stability and bioavailability of bioactive compounds. This study aimed at investigating the human microbial metabolism of quercetin derived from unformulated and phytosome-formulated quercetin through an in vitro model. Both ingredients were firstly characterized for their profile in native (poly)phenols, and then fermented with human fecal microbiota for 24 h. Quantification of microbial metabolites was performed by ultra-high performance liquid chromatography coupled to mass spectrometry (uHPLC-MSn) analyses. Native quercetin, the main compound in both products, appeared less prone to microbial degradation in the phytosome-formulated version compared to the unformulated one during fecal incubation. Quercetin of both products was bioaccessible to colonic microbiota, resulting in the production of phenylpropanoic acid, phenylacetic acid and benzoic acid derivatives. The extent of the microbial metabolism of quercetin was higher in the unformulated ingredient, in a time-dependent manner. This study opened new perspectives to investigate the role of delivery systems on influencing the microbial metabolism of flavonols in the colonic environment, a pivotal step in the presumed bioactivity associated to their intake.