Bioavailability and pharmacokinetic profile of grape pomace phenolic compounds in humans

Grape pomace, the major byproduct of the wine and juice industry, is a relevant source of bioactive phenolic compounds. However, polyphenol bioavailability in humans is not well understood, and the inter-individual variability in the production of phenolic metabolites has not been comprehensively assessed to date. The pharmacokinetic and excretive profiles of phenolic metabolites after the acute administration of a drink made from red grape pomace was here investigated in ten volunteers. A total of 35 and 28 phenolic metabolites were quantified in urine and plasma, respectively. The main circulating metabolites included phenyl-γ-valerolactones, hydroxybenzoic acids, simple phenols, hydroxyphenylpropionic acids, hydroxycinnamates, and (epi)catechin phase II conjugates. A high inter-individual variability was shown both in urine and plasma samples, and different patterns of circulating metabolites were unravelled by applying unsupervised multivariate analysis. Besides the huge variability in the production of microbial metabolites of colonic origin, an important variability was observed due to phase II conjugates. These results are of interest to further understand the potential health benefits of phenolic metabolites on individual basi

Effects of anthocyanin supplementation on serum lipids, glucose, markers of inflammation and cognition in adults with increased risk of dementia - A pilot study

Background: Anthocyanins may protect against cardiovascular related cognitive decline and dementia. Objective: Open-label study to measure changes in serum lipids, glucose, glycosylated hemoglobin (HbA1c), and markers of inflammation after anthocyanin supplementation in people with increased risk of dementia. As a secondary endpoint we examined potential changes in a battery of cognitive test in the anthocyanin group (AG). A total of 27 individuals with mild cognitive impairment (MCI) (n = 8) or stable non-obstructive coronary artery disease (CAD) (n = 19) consumed two Medox® capsules, each containing 80 mg of natural purified anthocyanins, twice daily for 16 weeks. They provided blood samples and performed a short battery of cognitive tests. Twenty healthy normal controls (NC) (n = 20) provided blood samples, but did not receive any intervention and did not perform cognitive tests. Results: There was a significant difference between groups for CCL-5/RANTES [regulated on activation, normal T-cell expressed and secreted (RANTES)]. In addition, total cholesterol and triglycerides were significantly increased in the AG. Improvements in memory and executive test scores were observed. No adverse effects were reported. Conclusion: The results of this pilot study were largely inconclusive with regard to the potential protective effects of anthocyanin supplementation. However, anthocyanins were well tolerated, and compliance was high. Larger, placebo-controlled studies to explore the potential effects of anthocyanins on dementia risk are encouraged.publishedVersio

Effect of Coffee and Cocoa-Based Confectionery Containing Coffee on Markers of DNA Damage and Lipid Peroxidation Products: Results from a Human Intervention Study

The effect of coffee and cocoa on oxidative damage to macromolecules has been investigated in several studies, often with controversial results. This study aimed to investigate the effect of one-month consumption of different doses of coffee or cocoa-based products containing coffee on markers of DNA damage and lipid peroxidation in young healthy volunteers. Twenty-one volunteers were randomly assigned into a three-arm, crossover, randomized trial. Subjects were assigned to consume one of the three following treatments: one cup of espresso coffee/day (1C), three cups of espresso coffee/day (3C), and one cup of espresso coffee plus two cocoa-based products containing coffee (PC) twice per day for 1 month. At the end of each treatment, blood samples were collected for the analysis of endogenous and H(2)O(2)-induced DNA damage and DNA oxidation catabolites, while urines were used for the analysis of oxylipins. On the whole, four DNA catabolites (cyclic guanosine monophosphate (cGMP), 8-OH-2′-deoxy-guanosine, 8-OH-guanine, and 8-NO2-cGMP) were detected in plasma samples following the one-month intervention. No significant modulation of DNA and lipid damage markers was documented among groups, apart from an effect of time for DNA strand breaks and some markers of lipid peroxidation. In conclusion, the consumption of coffee and cocoa-based confectionery containing coffee was apparently not able to affect oxidative stress markers. More studies are encouraged to better explain the findings obtained and to understand the impact of different dosages of these products on specific target groups

Effect of Coffee and Cocoa-Based Confectionery Containing Coffee on Markers of DNA Damage and Lipid Peroxidation Products: Results from a Human Intervention Study

The effect of coffee and cocoa on oxidative damage to macromolecules has been investigated in several studies, often with controversial results. This study aimed to investigate the effect of one-month consumption of different doses of coffee or cocoa-based products containing coffee on markers of DNA damage and lipid peroxidation in young healthy volunteers. Twenty-one volunteers were randomly assigned into a three-arm, crossover, randomized trial. Subjects were assigned to consume one of the three following treatments: one cup of espresso coffee/day (1C), three cups of espresso coffee/day (3C), and one cup of espresso coffee plus two cocoa-based products containing coffee (PC) twice per day for 1 month. At the end of each treatment, blood samples were collected for the analysis of endogenous and H2O2-induced DNA damage and DNA oxidation catabolites, while urines were used for the analysis of oxylipins. On the whole, four DNA catabolites (cyclic guanosine monophosphate (cGMP), 8-OH-2′-deoxy-guanosine, 8-OH-guanine, and 8-NO2-cGMP) were detected in plasma samples following the one-month intervention. No significant modulation of DNA and lipid damage markers was documented among groups, apart from an effect of time for DNA strand breaks and some markers of lipid peroxidation. In conclusion, the consumption of coffee and cocoa-based confectionery containing coffee was apparently not able to affect oxidative stress markers. More studies are encouraged to better explain the findings obtained and to understand the impact of different dosages of these products on specific target groups

Evaluation of the bioavailability and cardiometabolic effects of different dosages of coffee phytochemicals. Insights from an innovative acute/chronic intervention study

Coffee consumption is a moment of pleasure for many millions of people but, at the same time, coffee is an important source of bioactive compounds. This Doctoral Thesis reports the main findings of three year of research activity with coffee at its focus. The first part aimed to review the effect of coffee consumption on protection against lipid, protein and DNA damage. Overall, results suggest that coffee consumption can increase glutathione levels and improve protection against DNA damage, especially following regular/repeated intake. The characterization of 65 different capsule-brewed coffees, commercialised by 5 of the most representative brands in Italy, is described in chapter 2. An optimized UHPLC-MS/MS method allowed the detection and quantification of several phytochemicals in one single run and inter-lot and capsule variability was also evaluated for a subset of coffee capsules. Multivariate analysis provided comprehensive information on the phytochemical profile of the different types of coffee, showing a great variability among coffees with some brand-related insights. This study supports the need for an accurate characterization of the espresso coffees when intervention studies have to be designed and conducted for the investigation of the beneficial effects of coffee on human health. The last part of the Thesis describes the study design and the main results of a 3-arm crossover intervention aimed to investigate the bioavailability and beneficial properties of coffee bioactive compounds following coffee consumption at different dosages. In this framework, the contribution of cocoa-based products containing coffee to the pool of circulating metabolites, analysed by UHPLC-MS/MS, has also been considered. The findings of this study described the pharmacokinetic profiles of pyridines, phenolic metabolites and xanthines after the consumption of different coffee dosages. The obtained results allow to increase the knowledge related to coffee bioactives and their role on human health. Besides, they will be a starting point for future studies aimed to better understand the role of coffee on human health

Niacin, alkaloids and (poly)phenolic compounds in the most widespread Italian capsule-brewed coffees

Coffee is one of the most popular beverages worldwide and, nowadays, one of the most practical way for its preparation is by prepacked capsules. The aim of this study was comparing the content in caffeine, trigonelline, N-methylpyridinium (NMP), niacin, and chlorogenic acids of 65 different capsule-brewed coffees, commercialised by 5 of the most representative brands in Italy. Coffees were prepared from capsules following manufacturer’s instructions and analysed with an optimized UHPLC-MS/MS method able to assess all these phytochemicals in one single run. Inter-lot and capsule variability were also studied for a subset of coffee capsules. Except for decaffeinated coffees, caffeine amount accounted between 54 and 208 mg/serving. Regular espresso coffees showed higher trigonelline, NMP, and niacin concentrations than large (lungo) and decaffeinated samples, with average serving amounts of 17.96, 1.78, and 0.66 mg, respectively. Regarding chlorogenic acids, caffeoylquinic acids were the most relevant ones (20–117 mg/serving). Feruloylquinic acids were quantified between 8 and 50 mg/serving. Coumaroylquinic acids, hydroxycinnamate dimers, caffeoylshikimic acids, and caffeoylquinic lactones were also present at lower concentrations. Multivariate analysis provided comprehensive information on the phytochemical profile of the different types of coffee, showing a great variability among coffees with some brand-related insights. This study supports the need for accurately characterizing espresso coffees while investigating the beneficial effects of coffee on human health

The Pocket-4-Life project, bioavailability and beneficial properties of the bioactive compounds of espresso coffee and cocoa-based confectionery containing coffee: study protocol for a randomized cross-over trial

Abstract Background Coffee is an important source of bioactive compounds, including caffeine, phenolic compounds (mainly chlorogenic acids), trigonelline, and diterpenes. Several studies have highlighted the preventive effects of coffee consumption on major cardiometabolic diseases, but the impact of coffee dosage on markers of cardiometabolic risk is not well understood. Moreover, the pool of coffee-derived circulating metabolites and the contribution of each metabolite to disease prevention still need to be evaluated in real-life settings. The aim of this study will be to define the bioavailability and beneficial properties of coffee bioactive compounds on the basis of different levels of consumption, by using an innovative experimental design. The contribution of cocoa-based products containing coffee to the pool of circulating metabolites and their putative bioactivity will also be investigated. Methods A three-arm, crossover, randomized trial will be conducted. Twenty-one volunteers will be randomly assigned to consume three treatments in a random order for 1 month: 1 cup of espresso coffee/day, 3 cups of espresso coffee/day, and 1 cup of espresso coffee plus 2 cocoa-based products containing coffee twice per day. The last day of each treatment, blood and urine samples will be collected at specific time points, up to 24 hours following the consumption of the first product. At the end of each treatment the same protocol will be repeated, switching the allocation group. Besides the bioavailability of the coffee/cocoa bioactive compounds, the effect of the coffee/cocoa consumption on several cardiometabolic risk factors (anthropometric measures, blood pressure, inflammatory markers, trimethylamine N-oxide, nitric oxide, blood lipids, fasting indices of glucose/insulin metabolism, DNA damage, eicosanoids, and nutri-metabolomics) will be investigated. Discussion Results will provide information on the bioavailability of the main groups of phytochemicals in coffee and on their modulation by the level of consumption. Findings will also show the circulating metabolites and their bioactivity when coffee consumption is substituted with the intake of cocoa-based products containing coffee. Finally, the effect of different levels of 1-month coffee consumption on cardiometabolic risk factors will be elucidated, likely providing additional insights on the role of coffee in the protection against chronic diseases. Trial registration ClinicalTrials.gov, NCT03166540 . Registered on May 21, 2017

Phytochemical Profiling of Flavonoids, Phenolic Acids, Terpenoids, and Volatile Fraction of a Rosemary (Rosmarinus officinalis L.) Extract

This paper presents a comprehensive analysis of the phytochemical profile of a proprietary rosemary (Rosmarinus officinalis L.) extract rich in carnosic acid. A characterization of the (poly)phenolic and volatile fractions of the extract was carried out using mass spectrometric techniques. The (poly)phenolic composition was assessed by ultra-high performance liquid chromatography-electrospray ionization-mass spectrometry (UHPLC-ESI-MS(n)) and a total of 57 compounds were tentatively identified and quantified, 14 of these being detected in rosemary extract for the first time. The rosemary extract contained 24 flavonoids (mainly flavones, although flavonols and flavanones were also detected), 5 phenolic acids, 24 diterpenoids (carnosic acid, carnosol, and rosmanol derivatives), 1 triterpenoid (betulinic acid), and 3 lignans (medioresinol derivatives). Carnosic acid was the predominant phenolic compound. The volatile profile of the rosemary extract was evaluated by head space solid-phase microextraction (HS-SPME) linked to gas chromatography-mass spectrometry (GC-MS). Sixty-three volatile molecules (mainly terpenes, alcohols, esters, aldehydes, and ketones) were identified. This characterization extends the current knowledge on the phytochemistry of Rosmarinus officinalis and is, to our knowledge, the broadest profiling of its secondary metabolites to date. It can assist in the authentication of rosemary extracts or rosemary-containing products or in testing its bioactivity. Moreover, this methodological approach could be applied to the study of other plant-based food ingredients

(Poly)phenolic fingerprint and chemometric analysis of white (Morus alba L.) and black (Morus nigra L.) mulberry leaves by using a non-targeted UHPLC-MS approach

This study reports the (poly)phenolic fingerprinting and chemometric discrimination of leaves of eight mulberry clones from Morus alba and Morus nigra cultivated in Spain. UHPLC-MSn (Ultra High Performance Liquid Chromatography-Mass Spectrometry) high-throughput analysis allowed the tentative identification of a total of 31 compounds. The phenolic profile of mulberry leaf was characterized by the presence of a high number of flavonol derivatives, mainly glycosylated forms of quercetin and kaempferol. Caffeoylquinic acids, simple phenolic acids, and some organic acids were also detected. Seven compounds were identified for the first time in mulberry leaves. The chemometric analysis (cluster analysis and principal component analysis) of the chromatographic data allowed the characterization of the different mulberry clones and served to explain the great intraspecific variability in mulberry secondary metabolism. This screening of the complete phenolic profile of mulberry leaves can assist the increasing interest for purposes related to quality control, germplasm screening, and bioactivity evaluation