Reply to Rayman et al. Comment on "Ambra et al. Could Selenium Supplementation Prevent COVID-19? A Comprehensive Review of Available Studies. Molecules 2023, 28, 4130".

We thank the Authors of the Comment (AC) [...].

Could Selenium Supplementation Prevent COVID-19? A Comprehensive Review of Available Studies.

The purpose of this review is to systematically examine the scientific evidence investigating selenium's relationship with COVID-19, aiming to support, or refute, the growing hypothesis that supplementation could prevent COVID-19 etiopathogenesis. In fact, immediately after the beginning of the COVID-19 pandemic, several speculative reviews suggested that selenium supplementation in the general population could act as a silver bullet to limit or even prevent the disease. Instead, a deep reading of the scientific reports on selenium and COVID-19 that are available to date supports neither the specific role of selenium in COVID-19 severity, nor the role of its supplementation in the prevention disease onset, nor its etiology.

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.

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.

S. Giovanni Varieties (Pyrus communis L.): Antioxidant Properties and Phytochemical Characteristics.

In order to evaluate and identify the antioxidant properties and the phytochemical characteristics, as well as the role of the genetic background and the different fruit parts in the definition of fruit quality, we characterized the existing germplasm through nuclear simple sequence repeats (SSRs) and evaluated the genetic divergence between ancient S. Giovanni varieties (Pyrus communis L.) and different types of grafting in relation to some variables of fruit quality. On the peel and pulp of pear varieties, the contents of flavanols, flavonols, and hydroxycinnamic acids as well as total antioxidant capacity were assessed. Their role in plant defences was confirmed by a significantly higher amount in the peel (206.66 ± 44.27, 48.45 ± 13.65, and 31.11 ± 11.94 mg/100 g, respectively) of S. Giovanni pears than in the pulp (71.45 ± 34.94, 1.62 ± 0.83, and 17.05 ± 5.04 mg/100 g, respectively). Data obtained using capillary analysis of SSR indicate unequivocally that the four samples of San Giovanni varieties can be divided into 3 different genetic groups. Cultivar and the different parts of the fruit can exert an action in the definition of the quality product. The use of local varieties and ecotypes can be considered a valid tool to improve food quality and at the same time to support local agrobiodiversity.

The Potential Health Benefits of Polyphenol-Rich Extracts from Cichorium intybus L. Studied on Caco-2 Cells Model.

Phytochemicals can exert their bioactivity without reaching the systemic circulation; scarcely absorbed antioxidants might reach the large bowel contributing to protection from oxidative damage-induced gastrointestinal diseases. In the present work, we aimed to study the relationship between potential activity of polyphenol-rich extracts from Cichorium intybus L. and changes in morphological characteristics on Caco-2 cells. Phytochemicals content (carotenoids and flavonoids) and total antioxidant activity of Red Chicory of Treviso and Variegated Chicory of Castelfranco were evaluated. The bioactivity of polyphenol-rich extracts from chicories was studied in in vitro Caco-2 cell monolayers model. Morphological characteristics changes to test the antioxidant and/or prooxidant effect were verified by histological analysis and observed by Electronic Scansion Microscopy (SEM). On Caco-2 cell model, the polyphenols fractions from chicories have indicated a moderate antioxidant behavior until 17 µM concentration, while 70 µM and 34 µM exert cytotoxic effects for Treviso's and Castelfranco's Chicory, respectively, highlighted by TEER decreasing, increased permeability, and alteration of epithelium. Our findings support the beneficial effects of these products in counteracting the oxidative stress and cellular damage, induced in vitro on Caco-2 cell model, through interaction with the mucopolysaccharide complexes in the glycocalyx, maintaining in vivo a healthy and effective intestinal barrier.

Antioxidant Properties of Seeds from Lines of Artichoke, Cultivated Cardoon and Wild Cardoon.

The artichoke (Cynara cardunculus L. subsp. scolymus L.), the cultivated cardoon (Cynara cardunculus var. altilis DC.) and the wild cardoon (Cynara cardunculus var. sylvestris L.) are species widely distributed in the Mediterranean area. The aim of this research was to evaluate the antioxidant properties of seeds from lines of artichoke and cultivated and wild cardoon in both aqueous-organic extracts and their residues by FRAP (Ferric Reducing Antioxidant Power) and TEAC (Trolox Equivalent Antioxidant Capacity) evaluations. Both artichoke and cardoon seeds are a good source of antioxidants. Among artichoke seeds, hydrolysable polyphenols contribution to antioxidant properties ranged from 41% to 78% for FRAP values and from 17% to 37% for TEAC values. No difference between cultivated and wild cardoon in antioxidant properties are reported. Our results could provide information about the potential industrial use and application of artichoke and/or cardoon seeds.

Fatty acid content of serum lipid fractions and blood lipids in normolipidaemic volunteers fed two types of cheese having different fat compositions: a pilot study.

The aim of this randomised, double-blind, crossover study in normolipidaemic volunteers was to investigate the effect of consumption of an experimental cheese (from cows fed a grass and maize silage-based diet with 5% of linseed oil added) or a control cheese (without linseed oil) on both plasma lipids and fatty acid content of serum lipid fractions. A lower content of medium-chain saturated fatty acids as well as a higher content of stearic acid and polyunsaturated fatty acids were found in the experimental cheese; its consumption was successful in limiting the enhanced blood concentration of atherogenic fatty acids, without affecting fatty acid content of serum lipid fractions. These results indicate that dairy products could be considered as key foods for fat modifications with the objective of optimizing their nutritional quality.

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.

Differential effect of cheese fatty acid composition on blood lipid profile and redox status in normolipidemic volunteers: a pilot study.

The present study investigated the effect of the consumption of two cheese varieties differing for fat quality on blood lipid profile and redox status biomarkers in 30 selected healthy volunteers, consuming either the experimental cheese (from milk produced by cows fed a grass and maize silage based diet with 5% of linseed oil added) or the control cheese (from normal cows' milk) for 4 weeks according to a crossover design. The experimental cheese had a lower content of medium-chain saturated fatty acids and a higher content of stearic acid and polyunsaturated fatty acids; its consumption led to higher levels of vitamins C and E and stearic acid in blood, while myristic acid and oxidized low-density lipoprotein concentrations were significantly lower. As myristic acid and oxidized low-density lipoprotein are highly correlated with increased atherogenic risk and vitamins C and E with antioxidant activity, the enrichment of cows' diet with linseed oil could provide a dietary option to prevent cardiovascular diseases risk.

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.

No antioxidant beneficial effect of zinc supplementation on oxidative stress markers and antioxidant defenses in middle-aged and elderly subjects: the Zenith study.

OBJECTIVE: The aim of the study was to investigate whether zinc supplementation affects antioxidant status in European middle-aged and elderly people. DESIGN: Multicentre prospective intervention study, randomized, double-blind, placebo-control. SETTING: France (Clermont-Ferrand/Theix, and Grenoble), Italy (Rome), Northern Ireland (Coleraine). SUBJECTS: A total of 387 healthy middle-aged (55-70 yrs) and free-living older aged (70-85 yrs) subjects were randomly allocated to three groups: 0, 15 or 30 mg zinc gluconate/d in addition to usual dietary intake during 6 months. METHODS: Oxidative stress status was evaluated by measurement of protein oxidation (plasma thiol groups), lipid peroxidation (plasma thio-barbituric acid reactants, TBARS), whole blood glutathione levels, erythrocyte copper/zinc superoxide dismutase activity and plasma antioxidant status (ferric reducing antioxidant power assay), at baseline and after 3 and 6 months. RESULTS: Zinc supplementation did not alter oxidative stress markers and antioxidant defenses in elderly, after 3 or 6 months, except an increase in Cu/Zn superoxide dismutase activity. CONCLUSIONS: In apparently healthy free living elderly people, a single zinc supplementation had no effects on oxidative stress status.

Assessment of the nutritional values of genetically modified wheat, corn, and tomato crops.

The genetic modification in fruit and vegetables could lead to changes in metabolic pathways and, therefore, to the variation of the molecular pattern, with particular attention to antioxidant compounds not well-described in the literature. The aim of the present study was to compare the quality composition of transgenic wheat ( Triticum durum L.), corn ( Zea mays L.), and tomato ( Lycopersicum esculentum Mill.) to the nontransgenic control with a similar genetic background. In the first experiment, Ofanto wheat cultivar containing the tobacco rab1 gene and nontransgenic Ofanto were used. The second experiment compared two transgenic lines of corn containing Bacillus thuringiensis "Cry toxin" gene (PR33P67 and Pegaso Bt) to their nontransgenic forms. The third experiment was conducted on transgenic tomato ( Lycopersicum esculentum Mill.) containing the Agrobacterium rhizogenes rolD gene and its nontransgenic control (cv. Tondino). Conventional and genetically modified crops were compared in terms of fatty acids content, unsaponifiable fraction of antioxidants, total phenols, polyphenols, carotenoids, vitamin C, total antioxidant activity, and mineral composition. No significant differences were observed for qualitative traits analyzed in wheat and corn samples. In tomato samples, the total antioxidant activity (TAA), measured by FRAP assay, and the naringenin content showed a lower value in genetically modified organism (GMO) samples (0.35 mmol of Fe (2+) 100 g (-1) and 2.82 mg 100 g (-1), respectively), in comparison to its nontransgenic control (0.41 mmol of Fe (2+) 100 g (-1) and 4.17 mg 100 g (-1), respectively). On the basis of the principle of substantial equivalence, as articulated by the World Health Organization, the Organization for Economic Cooperation and Development, and the United Nations Food and Agriculture Organization, these data support the conclusion that GM events are nutritionally similar to conventional varieties of wheat, corn, and tomato on the market today.

Changes in antioxidant content of tomato fruits in response to cultivar and nutrient solution composition.

The aim of this study was to investigate the effect of cationic proportions (K/Ca/Mg) in the nutrient solution on fruit quality (quality attributes and antioxidant content) using a high-pigment, 'Lunarossa', tomato cultivar and a standard tomato cultivar ('Corfù') grown in soilless culture. Treatments were defined by a factorial combination of three nutrient solutions having different cationic proportions and two indeterminately growing round tomato cultivars. A high proportion of K in the nutrient solution increased the quality attributes (fruit dry matter, total soluble solids content) and the lycopene content of tomato fruit, whereas a high proportion of Ca improved tomato fruit yield and reduced the incidence of blossom-end rot (BER). The highest total antioxidant activity was observed in the treatment with a high proportion of Mg in the Lunarossa cultivar. The high-pigment hybrid has provided a higher antioxidant content (lycopene and alpha-tocopherol content) than the commercial hybrid, but it was more susceptible to BER and consequently less productive.