Paola Vitaglione

Dietary Antioxidant Compounds and Liver Health

Abstract Chronic liver damage is a widespread pathology characterized by a progressive evolution from steatosis to chronic hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. As the oxidative stress plays a central role in liver diseases pathogenesis and progression, the use of antioxidants have been proposed as therapeutic agents, as well as drug coadjuvants, to counteract liver damage. In this work in vitro and in vivo studies, with emphasis on humans and animals experiments, have been considered and reviewed according to antioxidant typologies. Great differences emerge as far as ingested doses, bioavailability and liver ability to accumulate the various compounds. Results available up to now suggest that lycopene-rich foods could be proposed in therapeutic treatment of some liver pathologies. On the other hand contradictory results have been obtained with α-tocopherol, β -carotene and trans-resveratrol. Quercetin, silymarin, esculetin and thyme and rosemary among phenolic compounds need further studies.

Polyphenols and Human Health: A Prospectus

The lay press often heralds polyphenols as panacea for all sorts of diseases. The rationale is that their antioxidant activity would prevent free radical damage to macromolecules. However, basic and clinical science is showing that the reality is much more complex than this and that several issues, notably content in foodstuff, bioavailability, or in vivo antioxidant activity are yet to be resolved. We summarize the recent findings concerning the effects of polyphenols on human health, analyze the current limitations at pitfalls, and propose future directions for research.

Coffee reduces liver damage in a rat model of steatohepatitis: the underlying mechanisms and the role of polyphenols and melanoidins.

Epidemiological data associate coffee consumption with a lower prevalence of chronic liver disease and a reduced risk of elevated liver enzyme levels (γ glutamyl transpeptidase and alanine aminotransferase), advanced liver disease and its complications, and hepatocellular carcinoma. Knowledge of the mechanisms underlying these effects and the coffee components responsible for these properties is still lacking. In this study, 1.5 mL/day of decaffeinated coffee or its polyphenols or melanoidins (corresponding to approximately 2 cups of filtered coffee or 6 cups of espresso coffee for a 70‐kg person) were added for 8 weeks to the drinking water of rats who were being fed a high‐fat, high‐calorie solid diet (HFD) for the previous 4 weeks. At week 12, HFD + water rats showed a clinical picture typical of advanced nonalcoholic steatohepatitis compared with control rats (normal diet + water). In comparison, HFD + coffee rats showed: (1) reduced hepatic fat and collagen, as well as reduced serum alanine aminotransferase and triglycerides; (2) a two‐fold reduced/oxidized glutathione ratio in both serum and liver; (3) reduced serum malondialdehyde (lipid peroxidation) and increased ferric reducing antioxidant power (reducing activity); (4) reduced expression of tumor necrosis factor α (TNF‐α), tissue transglutaminase, and transforming growth factor β and increased expression of adiponectin receptor and peroxisome proliferator‐activated receptor α in liver tissue; and (5) reduced hepatic concentrations of proinflammatory TNF‐α and interferon‐γ and increased anti‐inflammatory interleukin‐4 and interleukin‐10. Conclusion: Our data demonstrate that coffee consumption protects the liver from damage caused by a high‐fat diet. This effect was mediated by a reduction in hepatic fat accumulation (through increased fatty acid β‐oxidation); systemic and liver oxidative stress (through the glutathione system); liver inflammation (through modulation of genes); and expression and concentrations of proteins and cytokines related to inflammation. (HEPATOLOGY 2010;52:1652‐1661)

β-Glucan-enriched bread reduces energy intake and modifies plasma ghrelin and peptide YY concentrations in the short term

Dietary fibre consumption may help to control appetite and to reduce calorie intake. Underlying molecular mechanisms were not fully investigated. The aim of this study was to evaluate the effect of barley beta-glucans on short-term appetite and on satiety-related hormones in healthy subjects. Fourteen volunteers were selected and randomly assigned to have isocaloric breakfasts including a 3% beta-glucan-enriched bread (betaGB) or a control bread (CB). Post-breakfast individual self-records of appetite ratings and measure of calorie intake at an ad libitum lunch as well as measure of blood glucose, insulin, ghrelin and PYY concentrations, were performed. betaGB determined a significant higher reduction of hunger and increase of fullness and satiety than CB. Accordingly, a 19% reduction of energy intake at lunch subsequent to betaGB consumption compared to CB, was recorded. A 23% lower AUC(60-180) of plasma ghrelin and a 16% higher total AUC of PYY response after betaGB than CB consumption, independent from insulin response, was found. Glucose response was also blunted by betaGB vs CB. Barley beta-glucans were able to control appetite in the short term by modulating sensations and reducing energy intake. Data suggested for the first time that satiety effect of beta-glucans are mediated by ghrelin and PYY.

Whole-grain wheat consumption reduces inflammation in a randomized controlled trial on overweight and obese subjects with unhealthy dietary and lifestyle behaviors: role of polyphenols bound to cereal dietary fiber

BACKGROUND Epidemiology associates whole-grain (WG) consumption with several health benefits. Mounting evidence suggests that WG wheat polyphenols play a role in mechanisms underlying health benefits. OBJECTIVE The objective was to assess circulating concentration, excretion, and the physiologic role of WG wheat polyphenols in subjects with suboptimal dietary and lifestyle behaviors. DESIGN A placebo-controlled, parallel-group randomized trial with 80 healthy overweight/obese subjects with low intake of fruit and vegetables and sedentary lifestyle was performed. Participants replaced precise portions of refined wheat (RW) with a fixed amount of selected WG wheat or RW products for 8 wk. At baseline and every 4 wk, blood, urine, feces, and anthropometric and body composition measures were collected. Profiles of phenolic acids in biological samples, plasma markers of metabolic disease and inflammation, and fecal microbiota composition were assessed. RESULTS WG consumption for 4-8 wk determined a 4-fold increase in serum dihydroferulic acid (DHFA) and a 2-fold increase in fecal ferulic acid (FA) compared with RW consumption (no changes). Similarly, urinary FA at 8 wk doubled the baseline concentration only in WG subjects. Concomitant reduction in plasma tumor necrosis factor-α (TNF-α) after 8 wk and increased interleukin (IL)-10 only after 4 wk with WG compared with RW (P = 0.04) were observed. No significant change in plasma metabolic disease markers over the study period was observed, but a trend toward lower plasma plasminogen activator inhibitor 1 with higher excretion of FA and DHFA in the WG group was found. Fecal FA was associated with baseline low Bifidobacteriales and Bacteroidetes abundances, whereas after WG consumption, it correlated with increased Bacteroidetes and Firmicutes but reduced Clostridium. TNF-α reduction correlated with increased Bacteroides and Lactobacillus. No effect of dietary interventions on anthropometric measurements and body composition was found. CONCLUSIONS WG wheat consumption significantly increased excreted FA and circulating DHFA. Bacterial communities influenced fecal FA and were modified by WG wheat consumption. This trial was registered at clinicaltrials.gov as NCT01293175.

Mediterranean Diet and Cardiovascular Risk Factors: A Systematic Review

The aim of this paper was to systematically review and analyze the epidemiological evidence on the role of Mediterranean diet (MD) in the prevention of cardiovascular diseases (CVD). Fifty-eight studies exploring the relation between MD and lipoprotein concentration, antioxidative capacity and inflammatory markers, hypertension, obesity, diabetes, and metabolic syndrome, were identified and selected. These included 33 cross-sectional, 9 cohort, and 16 intervention studies. Most of the studies showed favorable effects of MD on CVD, although a certain degree of controversy remains in the respect of some issues, as obesity. Important methodological differences and limitations in the studies make difficult to compare results, thus further studies, particularly randomized clinical trials, are needed to finally substantiate the benefits of MD and to shed some lights on mechanisms.

Bioavailability of strawberry antioxidants in human subjects

Strawberries contain many antioxidant phytochemicals such as vitamin C, carotenoids and phenolic compounds including anthocyanins (ACN). In the present study, antioxidant composition of fresh strawberries (FS) and stored strawberries (SS) and the bioavailability of the main strawberry bioactive compounds were determined in human subjects. Thirteen healthy volunteers consumed 300 g of FS and SS on two separate occasions. Blood, before and at different time points from meal consumption, as well as 24 h urine, was collected, and parent compounds and metabolites of the different compounds were determined by HPLC or LC/MS/MS. A reduction in α-carotene plasma concentrations v. baseline values was recorded after the consumption of FS, although the amount of this carotenoid was higher in the SS. On the contrary, a significant increase of plasma vitamin C after 2, 3 and 5 h (P < 0.05) of FS and SS consumption was recorded. No quercetin and ACN were found in plasma, while coumaric acid, 4-hydroxybenzoic acid (4HBA, 56 and 54% of pelargonidin-3-glucoside (Pel-glc) ingested with FS and SS, respectively) and protocatechuic acid (59 and 34% of cyanidin-3-glucoside ingested with FS and SS, respectively) over 8 h from strawberry consumption were retrieved in the plasma. Pelargonidin glucuronide, pelargonidin glucoside and pelargonidin aglycone peaked in urine within 2 h of strawberry consumption, and the 24 h amount excreted was always approximately 0.9% of the Pel-glc dose ingested. The data indicated that the content of phytochemicals in strawberries may influence the bioavailability of individual compounds. Furthermore, in the present study, the metabolism of Pel-glc was elucidated, and, for the first time, 4HBA was suggested to be a major human metabolite of Pel-glc.

In vitro bioaccessibility and gut biotransformation of polyphenols present in the water‐insoluble cocoa fraction

SCOPE Cocoa, especially the water-insoluble cocoa fraction (WICF), is a rich source of polyphenols. In this study, sequential in vitro digestion of the WICF with gastrointestinal enzymes as well as its bacterial fermentation in a human colonic model system were carried out to investigate bioaccessibility and biotransformation of WICF polyphenols, respectively. METHODS AND RESULTS The yield of each enzymatic digestion step and the total antioxidant capacity (TAC) were measured and solubilized phenols were characterized by MS/MS. Fermentation of WICF and the effect on the gut microbiota, SCFA production and metabolism of polyphenols was analyzed. In vitro digestion solubilized 38.6% of WICF with pronase and Viscozyme L treatments releasing 51% of the total phenols from the insoluble material. This release of phenols does not determine a reduction in the total antioxidant capacity of the digestion-resistant material. In the colonic model WICF significantly increased of bifidobacteria and lactobacilli as well as butyrate production. Flavanols were converted into phenolic acids by the microbiota following a concentration gradient resulting in high concentrations of 3-hydroxyphenylpropionic acid (3-HPP) in the last gut compartment. CONCLUSION Data showed that WICF may exert antioxidant action through the gastrointestinal tract despite its polyphenols being still bound to macromolecules and having prebiotic activity.

Potential prebiotic activity of oligosaccharides obtained by enzymatic conversion of durum wheat insoluble dietary fibre into soluble dietary fibre

BACKGROUND AND AIMS Epidemiological evidence indicates that cereal dietary fibre (DF) may have several cardiovascular health benefits. The underlying mechanisms have not yet been elucidated. Here, the potential nutritional effects of physico-chemical properties modifications of durum wheat dietary fibre (DWF) induced by enzyme treatment have been investigated. METHODS AND RESULTS The conversion of the highly polymerised insoluble dietary fibre into soluble feruloyl oligosaccharides of DWF was achieved by a tailored enzymatic treatment. The in vitro fermentation and release of ferulic acid by intestinal microbiota from DWF before and after the enzymatic treatment were assessed using a gut model validated to mimic the human colonic microbial environment. Results demonstrated that, compared to DWF, the enzyme-treated DWF (ET-DWF) stimulated the growth of bifidobacteria and lactobacilli. Concurrently, the release of free ferulic acid by ET-DWF was almost three times higher respect to the control. No effect on the formation of short chain fatty acids was observed. CONCLUSIONS The conversion of insoluble dietary fibre from cereals into soluble dietary fibre generated a gut microbial fermentation that supported bifidobacteria and lactobacilli. The concurrent increase in free ferulic acid from the enzyme-treated DWF might result in a higher plasma ferulic acid concentration which could be one of the reasons for the health benefits reported for dietary fibre in cardiovascular diseases.

Beneficial Effects of the Mediterranean Diet on Metabolic Syndrome

The metabolic syndrome (MetS) represents a cluster of medical disorders, such as hyperglycemia, dyslipidemia, hypertension, and abdominal obesity that, when occurring together, increase the risk of developing cardiovascular disease. The role of food and nutrients in the aetiology of chronic diseases has become clearer over the last 15 years. In this review we collected evidence on the beneficial impact of the Mediterranean diet on MetS by analyzing epidemiological reports documenting its prevalence in subjects who have adopted this dietary pattern. We also explored the role of the individual components of the diet on the specific aspects characterizing the MetS (i.e. metabolic indices, body weight and blood pressure). There is ample evidence showing that subjects adherent to the Mediterranean diet have lower prevalence and incidence rates of MetS than non-adherent. Moreover, it has been widely documented that specific components of this dietary pattern play a role in the prevention of several morbid conditions related to the MetS.