Total and Plant Protein Consumption: The Role of Inflammation and Risk of Non-Communicable Disease.

Background: Inflammatory cytokine levels are associated with Non-Communicable Diseases (NCDs) and can be influenced by a person's macronutrient profile. This work aims to evaluate the relationship between the compliance with the age-specific recommended protein intake and the levels of inflammatory markers related to the risk of NCDs. Methods: The study participants included 347 participants (119 men and 228 women), ages 18 to 86 years. Cardio-metabolic risk evaluations, including an assessment of the prevalence of Metabolic Syndrome, were performed. Leptin, IL-15, IL-6, and TNF-α levels were measured. Results: The adequacy of the total protein (TP) intake was lower in old people compared to individuals aged <60 years, and only few volunteers consumed the suggested 50% plant protein (PP) for a healthy and sustainable diet. A lower risk of NCDs with a PP consumption above at least 40% was observed only in old individuals. A differential effect on TNF-α and IL-6 was observed for both TP and PP intake by gender and age class, whereas for leptin and IL-15 only significant interactions among sex and the class of age were found. Conclusion: Although our data suggest that consuming more than 40% of PP can reduce the risk of NCDs, the effect of gender differences on cytokine levels should be considered in larger studies.

Mediterranean Diet for the Prevention of Gestational Diabetes in the Covid-19 Era: Implications of Il-6 In Diabesity.

The aim of this review is to highlight the influence of the Mediterranean Diet (MedDiet) on Gestational Diabetes Mellitus (GDM) and Gestational Weight Gain (GWG) during the COVID-19 pandemic era and the specific role of interleukin (IL)-6 in diabesity. It is known that diabetes, high body mass index, high glycated hemoglobin and raised serum IL-6 levels are predictive of poor outcomes in coronavirus disease 2019 (COVID-19). The immunopathological mechanisms of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection include rising levels of several cytokines and in particular IL-6. The latter is associated with hyperglycemia and insulin resistance and could be useful for predicting the development of GDM. Rich in omega-3 polyunsaturated fatty acids, vitamins, and minerals, MedDiet improves the immune system and could modulate IL-6, C reactive protein and Nuclear Factor (NF)-κB. Moreover, polyphenols could modulate microbiota composition, inhibit the NF-κB pathway, lower IL-6, and upregulate antioxidant enzymes. Finally, adhering to the MedDiet prior to and during pregnancy could have a protective effect, reducing GWG and the risk of GDM, as well as improving the immune response to viral infections such as COVID-19.

Post-Exercise Ketosis, Salivary Uric Acid and Interleukin-6 after a Simulated Wheelchair Basketball Match.

BACKGROUND: Interleukin (IL)-6, total antioxidant capacity (TAC) and uric acid (UA) increase after exercise in able-bodied individuals. Wheelchair Basketball Athletes (WBA), having low muscle mass, could be at risk of post-exercise ketosis. OBJECTIVE: This study aimed to evaluate the post-exercise ketosis, IL-6, and antioxidant response, in WBA of the Italian National team, after a simulated match. METHODS: Dietary intakes, Starvation Symptoms Inventory (SSI), percentage of fat mass (FM%) and basal Respiratory Exchange Ratio (RER) and Basal Energy Expenditure (BEE), were evaluated. Salivary TAC, UA and IL-6 were measured: before (PreM), at the end (EM) and 20 minutes after (PostM) the match. Capillary glucose and ß-hydroxybutyrate (ßHB) were monitored. Percentage of Heart Rate Reserve (%HRR) was measured to evaluate exercise intensity. RESULTS: WBA had low carbohydrates (43.5% of daily energy intake (En)) and high fat (36.3% En) intakes. The increase in UA at PostM correlated with En (0.810, p<0.01) and was inversely related to ßHB at EM (-0.719, p<0.05). Furthermore, at PostM growing IL-6 levels correlated with BEE (0.778, p<0.05) and inversely related to FM% (-0.762, p<0.5) were found, which in turn was correlated to SSI (0.781, p<0.05). Also ßHB PostM correlated with SSI (0.761, p<0.05) but was inversely related to RER (-0.745, p<0.05) and En (-0.826, p<0.01). CONCLUSION: Our study suggests that some WBA should improve their dietary habit in order to prevent post-exercise ketosis and ameliorate the endogenous antioxidant response after exercise.

Dietary flavonoids: Nano delivery and nanoparticles for cancer therapy.

Application of nanotechnologies to cancer therapy might increase solubility and/or bioavailability of bioactive compounds of natural or synthetic origin and offers other potential benefits in cancer therapy, including selective targeting. In the present review we aim to evaluate in vivo studies on the anticancer activity of nanoparticles (NPs) obtained from food-derived flavonoids. From a systematic search a total of 60 studies were identified. Most of the studies involved the flavanol epigallocatechin-3-O-gallate and the flavonol quercetin, in both delivery and co-delivery (with anti-cancer drugs) systems. Moreover, some studies investigated the effects of other flavonoids, such as anthocyanins aglycones anthocyanidins, flavanones, flavones and isoflavonoids. NPs inhibited tumor growth in both xenograft and chemical-induced animal models of cancerogenesis. Encapsulation improved bioavailability and/or reduced toxicity of both flavonoids and/or co-delivered drugs, such as doxorubicin, docetaxel, paclitaxel, honokiol and vincristine. Moreover, flavonoids have been successfully applied in molecular targeted nanosystems. Selectivity for cancer cells involves pH- and/or reactive oxygen species-mediated mechanisms. Furthermore, flavonoids are good candidates as drug delivery for anticancer drugs in green synthesis systems. In conclusion, although human studies are needed, NPs obtained from food-derived flavonoids have promising anticancer effects in vivo.

Evaluation of adherence to Mediterranean diet and association with clinical and biological markers in an Italian population.

OBJECTIVES: The purpose of this study was to evaluate the overall diet quality of an Italian population through the use of the Mediterranean Diet Serving Score (MDSS) and its relation to clinical and biochemical nutritional markers. METHODS: The study was conducted on healthy participants ages 18 to 86 y living in central Italy. Adherence to the Mediterranean food pattern was evaluated by a semiquantitative food frequency, using the MDSS. Anthropometric measurements and biochemical analyses of nutritional interest were performed according to the standardized procedure. RESULTS: The sample included a total of 349 participants (121 men and 228 women) with an average age of 54 ± 15 y and a body mass index of 27.4 ± 4.8 kg/m2, underlining an overweight status in both men and women. The mean educational level was medium-high in both sexes, whereas the occupation level was higher in women than in men (P = 0.001). The mean MDSS score was 14.4 ± 4.1 out of a total of 24 points. The adherence was higher in women (score 14.7 ± 3.9) than men (score 13.9 ± 4.4), although there were no significant differences (P = 0.25). No statistical differences in MDSS were found in relation to body mass index and educational level, whereas a higher MDSS score was observed in the older age group (P < 0.05). A positive correlation among MDSS, high-density lipoprotein cholesterol, and vitamin C has been found (P < 0.05), whereas there was a negative correlation with uric acid and triacylglycerols (P < 0.05). A logistic regression analysis highlighted smoking habit as the only predictive factor for a high adherence to MDSS (P < 0.05). CONCLUSIONS: MDSS has a low adherence to the Mediterranean diet, particularly in the youngest age group and smokers. The index shows a correlation with some parameters of nutritional interest and further larger cohorts studies are needed to confirm our findings.

Effects of High Consumption of Vegetables on Clinical, Immunological, and Antioxidant Markers in Subjects at Risk of Cardiovascular Diseases.

High intakes of vegetables have been associated with a lower incidence of cardiovascular diseases (CVD). However, the effect of vegetables on immune function and antioxidant status in human studies have provided contrasting results. In the present study, after a week of run-in period, 38 subjects at risk of CVD were randomly assigned to one of the following 4-week interventions: low vegetable consumption (800 g of vegetables/week) or high vegetable consumption (4200 g of vegetables/week). Vegetables included carrots, topinambur (Jerusalem artichoke, Helianthus tuberosus), tomatoes, red cabbage, and sweet peppers. Blood and salivary samples were collected before and after intervention periods. In addition to clinical, immunological, and antioxidant markers, leukocyte and lymphocyte expression of the gut-homing ß7 integrin was evaluated. No significant changes were detected in clinical, immunological, and antioxidant markers in biological samples, except for an increase in white blood cell count for the low vegetable consumption group (p < 0.05). The study provides additional evidence about the uncertainty of providing a clear evidence for vegetables in modulating markers of immune function and antioxidant status. Further studies are needed in order to unravel the mechanism of effect of vegetable consumption in cardiovascular prevention.

Redox Role of Lactobacillus casei Shirota Against the Cellular Damage Induced by 2,2'-Azobis (2-Amidinopropane) Dihydrochloride-Induced Oxidative and Inflammatory Stress in Enterocytes-Like Epithelial Cells.

In western societies where most of the day is spent in the postprandial state, the existence of oxidative and inflammatory stress conditions makes postprandial stress an important factor involved in the development of cardiovascular risk factors. A large body of evidence have been accumulated on the anti-inflammatory effects of probiotics, but no information is available on the mechanisms through which intestinal microbiota modulates redox unbalance associated with inflammatory stress. Here, we aimed to investigate the ability of Lactobacillus casei Shirota (LS) to induce an antioxidant response to counteract oxidative and inflammatory stress in an in vitro model of enterocytes. Our results show that pretreatment of enterocytes with LS prevents membrane barrier disruption and cellular reactive oxygen species (ROS) accumulation inside the cells, modulates the expression of the gastro-intestinal glutathione peroxidase (GPX2) antioxidant enzyme, and reduces p65 phosphorylation, supporting the involvement of the Nfr2 and nuclear factor kappa B pathways in the activation of antioxidant cellular defenses by probiotics. These results suggest, for the first time, a redox mechanism by LS in protecting intestinal cells from AAPH-induced oxidative and inflammatory stress.

Consumption of mixed fruit-juice drink and vitamin C reduces postprandial stress induced by a high fat meal in healthy overweight subjects.

Postprandial stress induced by acute consumption of meals with a high fat content results in an increase of markers of cardiometabolic risk. Repeated acute dietary stress may induce a persistent low-grade inflammation, playing a role in the pathogenesis of functional gut diseases. This may cause an impairment of the complex immune response of the gastrointestinal mucosa, which results in a breakdown of oral tolerance. We investigated the effect of ingestion of a fruit-juice drink (FJD) composed by multiple fruit juice and extracts, green tea extracts and vitamin C on postprandial stress induced by a High Fat Meal (HFM) in healthy overweight subjects. Following a double blind, placebo controlled, cross-over design, 15 healthy overweight subjects were randomized to a HFM providing 1334 Kcal (55% fat, 30% carbohydrates and 15% proteins) in combination with 500 mL of a placebo drink (HFM-P) or a fruit-juice drink (HFM-FJD). Ingestion of HFM-P led to an increase in circulating levels of cholesterol, triglycerides, glucose, insulin, TNF-α and IL-6. Ingestion of HFM-FJD significantly reduced plasma levels of cholesterol and triglycerides, decreasing inflammatory response mediated by TNF-α and IL-6. Ingestion of a fruit-juice drink reduce markers of postprandial stress induced by a HFM.

Fruit juice drinks prevent endogenous antioxidant response to high-fat meal ingestion.

High-fat meals (HFM) induce metabolic stress, leading to the activation of protective mechanisms, including inflammation and endogenous antioxidant defences. In the present study, we investigated the effects of antioxidant-rich fruit juice drinks on the endogenous antioxidant response induced by HFM. In a double-blind, cross-over design (10 d washout), fourteen overweight volunteers were randomly assigned to one of the following interventions: HFM+500 ml placebo beverage (HFM-PB, free from fruit); HFM+500 ml antioxidant beverage 1 (HFM-AB1; apple, grape, blueberry and pomegranate juices and grape skin, grape seed and green tea extracts); HFM+500 ml antioxidant beverage 2 (HFM-AB2; pineapple, black currant and plum juices). HFM-PB consumption increased the plasma levels of thiols (SH) (4 h, P< 0·001) and uric acid (UA) (2 h, P< 0·01) and total radical-trapping antioxidant parameter (TRAP) (4 h, P< 0·01). Following the consumption of drinks, UA production was significantly reduced with respect to placebo beverage consumption 8 h after HFM-AB2 consumption (P< 0·05). SH levels were reduced 0·5 (P< 0·05), 1 (P< 0·05) and 2 h (P< 0·01) after HFM-AB1 consumption and 2, 4 and 8 h (P< 0·05) after HFM-AB2 consumption. Plasma TRAP (2 h, P< 0·001) and urinary ferric reducing antioxidant power (0-8 h, P< 0·01) were increased by HFM-AB1 consumption, the drink with the highest in vitro antioxidant capacity, but not by HFM-AB2 consumption. In urine, UA levels were significantly increased from basal levels after the consumption of HFM-PB and HFM-AB2. However, neither of the beverages increased the urinary excretion of UA with respect to the placebo beverage. In conclusion, the increase in UA and SH levels induced by HFM as part of an endogenous antioxidant response to postprandial stress can be prevented by the concomitant ingestion of antioxidant-rich fruit juice drinks.

Effect of flavonoids on circulating levels of TNF-α and IL-6 in humans: a systematic review and meta-analysis.

Epidemiological or in vitro evidence suggests a potential role for flavonoids as anti-inflammatory agents; we investigated the effect of flavonoids-rich foods or supplements on tumor necrosis factor- alpha (TNF-α) and interleukin-6 (IL-6) in long-term placebo-controlled human intervention trials. From 110 human intervention studies selected (MEDLINE, EMBASE, CHORANE, and FSTA databases), 32 long-term placebo-controlled trials were suitable for meta-analysis. After sensitivity analysis, seven studies imputed of bias were excluded and 25 studies were analyzed (TNF-α, n = 2404; IL-6, n = 2174). Levels of TNF-α decreased after flavonoid consumption in the fixed model only (mean difference (MD) (95% CI): -0.098 (-0.188, -0.009), p = 0.032), but metaregression results showed that neither higher dose, nor a longer duration of intervention were associated with a greater effect size. Subgroup analysis did not reveal any significant effect for quercetin and soy, but other sources (red wine, pomegranate, and tea extracts) showed a significant effect size both in fixed (MD (95% CI): TNF-α -0.449 (-0.619, -0.280), p < 0.001; IL-6 -0.346 (-0.612, -0.079), p = 0.011) and random (MD (95% CI): TNF-α -0.783 (-1.476, -0.090), p = 0.027; IL-6, -0.556 (-1.062, -0.050), p = 0.031) effect models. High-quality placebo-controlled trials are needed in order to identify flavonoids as the active ingredients.

Antioxidant and inflammatory response following high-fat meal consumption in overweight subjects.

PURPOSE: Postprandial metabolic stress as a consequence of ingestion of high-energy meals is recognized as an important risk factor for cardiovascular disease. The objective of this study was to evaluate the inflammatory and antioxidant response of the body to the acute ingestion of a high-fat meal (HFM). METHODS: Fifteen healthy overweight subjects were recruited for the study. After HFM consumption, plasma glucose, insulin, uric acid (UA), triglycerides (TG), total cholesterol (TC), thiols (SH), inflammatory cytokines (IL-6 and TNF-α) and dietary antioxidants were measured at 0, 0, 5, 1, 2, 4, 6 and 8 h points from ingestion. RESULTS: The ingestion of HFM induced significant increases in both TG and TC, with peaks at 4 h (p < 0.001) and 8 h (p < 0.01), respectively. IL-6 and TNF-α significantly increased postprandially, reaching maximum concentrations 8 h after meal consumption (p < 0.001). Whereas plasma concentrations of vitamins and carotenoids were not changed by HFM, SH and UA increased, peaking 2-4 h postingestion (p < 0.001 and 0.01, respectively). Increments of SH and UA were positively correlated with AUC for TG (Pearson coefficient 0.888, p < 0.001 and 0.923, p < 0.001, respectively). CONCLUSIONS: Present results indicate that as a consequence of an excess of dietary fat, the body responds through an inflammatory reaction, which is accompanied by an increment of endogenous antioxidant defenses, mediated by UA and SH, but not by vitamins C and E and carotenoids. Although further studies are needed, results of the current investigation represent novel findings on endogenous strategies of redox defense from fat overloads.

High fat meal increase of IL-17 is prevented by ingestion of fruit juice drink in healthy overweight subjects.

An emerging role of IL-17 in the inflammatory response associated with pathogenesis of neurodegeneration has been recently suggested. However, though diet represents a key factor in the modulation of inflammatory processes, evidence is not currently available on the nutritional regulation of IL-17 in humans. In a double blind, randomized, placebo controlled, crossover study, we investigated the effect of High Fat Meal (HFM) on IL-17 circulating levels in presence of a placebo (HFM-P) or with a Fruit Juice Drink (HFM-FJD) composed of pineapple, blackcurrant and plum in fourteen healthy overweight humans. Fasting in the morning subjects ingested a test meal providing 1344 Kcal. Ingestion of HFM-P induced an inflammatory response mediated by TNF-α (p < 0.001), IL-6 (p < 0.001) and IL-17 (p < 0.01). Plasma IL-17 concentration significantly increased at 1 h (+2.6 ± 1.1 pg/ml), remaining high at 4 h (+2.98 ± 1.2 pg/ml), 6 h (+2.38 ± 0.6 pg/ml) and 8 h (+2.8 ± 0.9 pg/ml) (ANOVA for time-course p=0.009). When the HFM was consumed in the presence of the FJD a marked inhibition of IL-17 response to the HFM was observed (ANOVA between treatment p=0.037). We provided, for the first time, evidence on the role of diet in modulating IL-17 production in healthy overweight subjects.

Mediterranean Diet Effect: an Italian picture.

BACKGROUND: The purpose of this study was to evaluate the overall diet quality effects, mainly on antioxidant nutritional status and some cytokines related to the cellular immune response as well as oxidative stress in a healthy Italian population group. METHODS: An observational study was conducted on 131 healthy free-living subjects. Dietary intake was assessed by dietary diary. Standardised procedures were used to make anthropometric measurements. On blood samples (serum, plasma and whole blood) were evaluated: antioxidant status by vitamin A, vitamin E, carotenoids, vitamin C, uric acid, SH groups, SOD and GPx activities; lipid blood profile by total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides; total antioxidant capacity by FRAP and TRAP; the immune status by TNF-α, and IL-10 cytokines; the levels of malondialdehyde in the erythrocytes as marker of lipid peroxidation. RESULTS: The daily macronutrients intake (g/day) have shown a high lipids consumption and significant differences between the sexes with regard to daily micronutrients intake. On total sample mean Mediterranean Diet Score (MDS) was 4.5 ± 1.6 and no significant differences between the sexes were present. A greater adherence to a Mediterranean dietary pattern increases the circulating plasma levels of carotenoids (lutein plus zeaxanthin, cryptoxanthin, α and ß-carotene), vitamin A and vitamin E. The levels of endogenous antioxidants were also improved. We observed higher levels in anti-inflammatory effect cytokines (IL-10) in subjects with MDS ≥ 6, by contrast, subjects with MDS ≤ 3 show higher levels in sense of proinflammatory (TNF α P < 0.05). Lower levels of MDA were associated with MDS > 4. Our data suggest a protective role of vitamin A against chronic inflammatory conditions especially in subjects with the highest adherence to the Mediterranean-type dietary pattern. CONCLUSIONS: Mediterranean dietary pattern is associated with significant amelioration of multiple risk factors, including a better cardiovascular risk profile, reduced oxidative stress and modulation of inflammation.

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.

Effect of acute ingestion of fresh and stored lettuce (Lactuca sativa) on plasma total antioxidant capacity and antioxidant levels in human subjects.

The present study investigated whether storage under modified-atmosphere packaging (MAP) affected the antioxidant properties of fresh lettuce (Lactuca sativa). Eleven healthy volunteers (six men, five women) consumed 250 g fresh lettuce, and blood was sampled before (0 h) and 2, 3 and 6 h after consumption. The protocol was repeated 3 d later with the same lettuce stored at 5 degrees C under MAP conditions (O2-N2 (5:95, v/v)). Results showed that after ingestion of fresh lettuce, plasma total radical-trapping antioxidant potential (TRAP), measured as area under the curve, was significantly higher (1.3 (sem 0.3) mmol/l per 6 h; P<0.05) than the value obtained with MAP-stored lettuce (0.1 (sem 0.2) mmol/l per 6 h). Plasma TRAP, quercetin and p-coumaric acid were significantly different from baseline values (P