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Context: There is scarce evidence about which probiotic, prebiotic, or synbiotic supplementation is the most appropriate to improve sarcopenia parameters, and this presents a challenge., Objective: The effects of consumption of probiotics, prebiotics, and synbiotics on sarcopenia, muscle strength, muscle mass, and physical performance and function were assessed in this study. In addition, another aim of the study was to determine the best probiotic, prebiotic, and/or synbiotic for the management of sarcopenia in older adults., Data Sources: A systematic search was conducted in the MEDLINE/PubMed, Cochrane Library, SCOPUS databases, and other sources (eg, references obtained from articles identified in databases)., Data Extraction: The search was limited from 2000 to 2023 and was based on sarcopenia parameters, and probiotics, prebiotics, or synbiotics supplementation. The quality of each included study also was assessed., Data Analysis: A meta-analysis was performed with the Review Manager program and publication bias and sensitivity analysis were performed., Results: Eight randomized controlled trials (RCTs) were included in the systematic review and 4 in the meta-analysis. Results showed that probiotics supplementation improved muscle strength and physical performance and function and suggested a beneficial effect on muscle mass. Prebiotics are suggested to be effective on muscle strength. The meta-analysis also determined that probiotic interventions were effective in increasing muscle strength by handgrip strength (mean difference [MD], 2.50 kg [95% CI, 1.33-3.66]; P < .0001) and physical performance and function by gait speed (MD, 0.10 m/s [95% CI, 1.33-3.66]; P < .0001) and physical performance and function by gait speed (MD, 0.10 m/s [95%CI, 0.03-0.16]; P = .003), but when sensitivity analysis was applied, the effectiveness was only maintained for gait speed., Conclusion: Nutritional strategies based on probiotic supplementation seem to improve muscle strength and physical function. More robust research is needed with high-quality RCTs to confirm probiotics' effects. There is still limited evidence about prebiotic and synbiotic strategies, and more evidence is needed to elucidate their effects on sarcopenia parameters., Systematic Review Registration: PROSPERO registration no. CRD42022360514., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Life Sciences Institute.)

Objectives: The objective of this study was to assess the influence of the European Youth Tackling Obesity-Kids (EYTO-Kids) 10-month intervention, based on social marketing and peer-led methodologies, at 16 month of its ending., Study Design: Children (aged 9 at baseline and 11 at the follow-up) from disadvantaged neighbourhoods who participated in the 10-month EYTO-Kids parallel-cluster randomised controlled intervention study in Reus (Spain) were included. The number of participants was 252 (retention rate: 67.2%) in the intervention group (7 schools) and 226 (retention rate: 69.1%) in the control one (8 schools). Primary (physical activity and fruit consumption) and secondary (screen time; and vegetables, fast food, and sugary drink consumption) outcomes were assessed., Results: At follow-up, consumption of ≥1 fruit per day increased in girls (odds ratio [OR] (95% confidence interval [CI]) = 2.28 (1.2; 4.2), P = 0.012) and all children (OR (95%CI) = 2.28 (1.0; 2.6), P = 0.044) in the intervention group vs. the control one. Physical activity ≥6 h/week similarly increased in both groups., Conclusion: At long-term effectiveness of a 10-month intervention on improving fruit consumption in children was observed. Therefore, peer-led and social marketing methodologies enhance healthy lifestyles by conveying children towards healthy choices., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Personalized nutrition (PN) has been proposed as a strategy to increase the effectiveness of dietary recommendations and ultimately improve health status., Objectives: We aimed to assess whether including omics-based PN in an e-commerce tool improves dietary behavior and metabolic profile in general population., Methods: A 21-wk parallel, single-blinded, randomized intervention involved 193 adults assigned to a control group following Mediterranean diet recommendations (n = 57, completers = 36), PN (n = 70, completers = 45), or personalized plan (PP, n = 68, completers = 53) integrating a behavioral change program with PN recommendations. The intervention used metabolomics, proteomics, and genetic data to assist participants in creating personalized shopping lists in a simulated e-commerce retailer portal. The primary outcome was the Mediterranean diet adherence screener (MEDAS) score; secondary outcomes included biometric and metabolic markers and dietary habits., Results: Volunteers were categorized with a scoring system based on biomarkers of lipid, carbohydrate metabolism, inflammation, oxidative stress, and microbiota, and dietary recommendations delivered accordingly in the PN and PP groups. The intervention significantly increased MEDAS scores in all volunteers (control-3 points; 95% confidence interval [CI]: 2.2, 3.8; PN-2.7 points; 95% CI: 2.0, 3.3; and PP-2.8 points; 95% CI: 2.1, 3.4; q < 0.001). No significant differences were observed in dietary habits or health parameters between PN and control groups after adjustment for multiple comparisons. Nevertheless, personalized recommendations significantly (false discovery rate < 0.05) and selectively enhanced the scores calculated with biomarkers of carbohydrate metabolism (β: -0.37; 95% CI: -0.56, -0.18), oxidative stress (β: -0.37; 95% CI: -0.60, -0.15), microbiota (β: -0.38; 95% CI: -0.63, -0.15), and inflammation (β: -0.78; 95% CI: -1.24, -0.31) compared with control diet., Conclusions: Integration of personalized strategies within an e-commerce-like tool did not enhance adherence to Mediterranean diet or improved health markers compared with general recommendations. The metabotyping approach showed promising results and more research is guaranteed to further promote its application in PN. This trial was registered at clinicaltrials.gov as NCT04641559 (https://clinicaltrials.gov/study/NCT04641559?cond=NCT04641559&rank=1)., (Copyright © 2024. Published by Elsevier Inc.)

The study determines the sustained and acute effects of a red-fleshed apple (RFA), rich in anthocyanins (ACNs), a white-fleshed apple (WFA) without ACNs, and an infusion from Aronia melanocarpa (AI) with an equivalent content of ACNs as RFA, on different cardiometabolic risk biomarkers in hypercholesterolemic subjects. A randomized, parallel study was performed for 6 weeks and two dose-response studies were performed at the baseline and after intervention. At 6 weeks, RFA consumption improved ischemic reactive hyperemia and decreased C-reactive protein and interleukine-6 compared to WFA consumption. Moreover, at 6 weeks, AI decreased P-selectin compared to WFA and improved the lipid profile. Three products reduced C1q, C4 and Factor B, and RFA and AI reduced C3. Although both RFA and AI have a similar ACN content, RFA, by a matrix effect, induced more improvements in inflammation, whereas AI improved the lipid profile. Anti-inflammatory protein modulation by proteomic reduction of the complement system and immunoglobulins were verified after WFA, AI and RFA consumption.

Background: Low muscle mass quantity/quality is needed to confirm sarcopenia diagnosis; however, no validated cut-off points exist. This study aimed to determine the diagnostic accuracy of sarcopenia through muscle mass quantity/quality parameters, using the bioimpedance analysis (BIA), isokinetic, and ultrasound tools in probable sarcopenic community-dwelling older adults (≥60 years). Also, it aimed to suggest possible new cut-off points to confirm sarcopenia diagnosis., Methods: A cross-sectional exploratory analysis study was performed with probable sarcopenic and non-sarcopenic older adults. BIA, isokinetic, and ultrasound parameters were evaluated. The protocol was registered on ClinicalTrials.gov (NCT05485402)., Results: A total of 50 individuals were included, 38 with probable sarcopenia (69.63 ± 4.14 years; 7 men and 31 women) and 12 non-sarcopenic (67.58 ± 4.54 years; 7 men and 5 women). The phase angle (cut-off: 5.10° men, p = 0.003; 4.95° women, p < 0.001), peak torque (cut-off: 66.75 Newtons-meters (N-m) men, p < 0.001; 48.35 N-m women, p < 0.001), total work (cut-off: 64.00 Joules (J) men, p = 0.007; 54.70 J women, p = 0.001), and mean power (cut-off: 87.8 Watts (W) men, p = 0.003; 48.95 W women, p = 0.008) in leg extension, as well as the the forearm muscle thickness (cut-off: 1.41 cm (cm) men, p = 0.017; 0.94 cm women, p = 0.041), had great diagnostic accuracy in both sexes., Conclusions: The phase angle, peak torque, total work, and mean power in leg extension, as well as forearm muscle thickness, had great diagnostic accuracy in regard to sarcopenia, and the suggested cut-off points could lead to the confirmation of sarcopenia diagnosis, but more studies are needed to confirm this.

Hypertriglyceridemia (HTG) is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD). One of the multiple origins of HTG alteration is impaired lipoprotein lipase (LPL) activity, which is an emerging target for HTG treatment. We hypothesised that early, even mild, alterations in LPL activity might result in an identifiable metabolomic signature. The aim of the present study was to assess whether a metabolic signature of altered LPL activity in a preclinical model can be identified in humans. A preclinical LPL-dependent model of HTG was developed using a single intraperitoneal injection of poloxamer 407 (P407) in male Wistar rats. A rat metabolomics signature was identified, which led to a predictive model developed using machine learning techniques. The predictive model was applied to 140 humans classified according to clinical guidelines as (1) normal, less than 1.7 mmol/L; (2) risk of HTG, above 1.7 mmol/L. Injection of P407 in rats induced HTG by effectively inhibiting plasma LPL activity. Significantly responsive metabolites (i.e. specific triacylglycerols, diacylglycerols, phosphatidylcholines, cholesterol esters and lysophospholipids) were used to generate a predictive model. Healthy human volunteers with the impaired predictive LPL signature had statistically higher levels of TG, TC, LDL and APOB than those without the impaired LPL signature. The application of predictive metabolomic models based on mechanistic preclinical research may be considered as a strategy to stratify subjects with HTG of different origins. This approach may be of interest for precision medicine and nutritional approaches., (© 2023. The Author(s).)

The consumption of out-of-home meals is increasing. This study is aimed at assessing the effect of an intervention on healthy offerings and the management of food allergies and intolerances. Ten (control group) and eight restaurants (intervention group) were randomized in a 12-month parallel controlled trial. The outcomes were changes regarding adherence to the Mediterranean diet (AMed) and gluten management (SMAP) criteria, the traffic light rating category, nutrients, and gluten- and allergen-free content of dishes. After 12 months, and compared with baseline, there was an improvement of ≥25% in four items of the AMed criteria in the intervention group, whereas an increase in the offer of dairy desserts without added sugar, and a decrease in the first course offerings of vegetables and/or legumes were observed in the control group ( p < 0.05). Also, after 12 months, there was an improvement of ≥50% in four SMAP criteria ( p < 0.05) and in the mean average of all SMAP criteria ( p = 0.021) compared with baseline in the intervention group, in which intra- and inter-group improvements for desserts in traffic light ratings, nutrients, and allergens were observed ( p < 0.05). Therefore, the intervention showed beneficial effects, improving the quality of menus toward the Mediterranean diet pattern and gluten and food allergy/intolerance management.

Context: Dietary fatty acids (FAs), primarily n-3 polyunsaturated FAs, have been associated with enrichment of the circulating bioactive lipidome and changes in the enzymatic precursor lipoprotein-associated phospholipase A2 (Lp-PLA2) mass; however, the magnitude of this effect remains unclear., Objective: The aim of this systematic review and meta-analysis was to evaluate the effect of different dietary FAs on the bioactive lipid profile of healthy participants and those with cardiovascular disease (CVD) and CVD risk factors., Data Sources: PubMed, SCOPUS and the Cochrane Library databases were searched for relevant articles published between October 2010 and May 2022., Data Extraction: Data were screened for relevance and then retrieved in full and evaluated for eligibility by 2 reviewers independently., Data Analysis: The net difference in the bioactive lipid mean values between the endpoint and the baseline, and the corresponding SDs or SEs, were used for the qualitative synthesis. For the meta-analysis, a fixed-effects model was used., Results: Twenty-seven randomized clinical trials (representing >2560 participants) were included. Over 78% of the enrolled participants had ≥1 associated CVD risk factor, whereas <22% were healthy. In the meta-analysis, marine n-3 supplements (dose range, 0.37-1.9 g/d) significantly increased pro-inflammatory lysophosphatidylcholines (lyso-PCs; for lyso-PC(16:0): mean, +0.52 [95% confidence interval (CI), 0.02-1.01] µM; for lyso-PC(18:0): mean, +0.58 [95%CI, 0.09-1.08] µM) in obese participants. Additionally, n-3 supplementation (1-5.56 g/d) decreased plasma Lp-PLA2 mass, a well-known inflammation marker, in healthy (-0.35 [95%CI, -0.59 to -0.10] ng/mL), dyslipidemic (-0.36 [95%CI, -0.47 to -0.25] ng/mL), and stable coronary artery disease participants (-0.52 [95%CI, -0.91 to -0.12] ng/mL)., Conclusions: Daily n-3 provided as EPA+DHA supplements and consumed from 1 to 6 months reduced plasma Lp-PLA2 mass in healthy participants and those with CVD and CVD risk factors, suggesting an anti-inflammatory effect. However, the saturated lyso-PC response to n-3 was impaired in obese participants., Systematic Review Registration: PROSPERO registration no. CRD42021218335., (© The Author(s) 2022. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background & Aims: Sarcopenia is a disabling muscular multifactorial disease involving the oxidation process in old-young adults. We aimed to evaluate the relationship between antioxidant-rich foods (A-RF) and sarcopenia (muscle mass, strength, and function) based on observational studies (OS), and to assess the effectiveness of antioxidant interventions in ≥55-year-old adults via randomized controlled trials (RCTs). Moreover, to confirm if the OS results were in accordance with the RCTs results., Methods: We searched in the MEDLINE®/PubMed, Cochrane Library, and CINAHL databases from 2000 to 2020 about sarcopenia and specific nutrients/foods. The risk of bias was assessed and meta-analyses were performed using the Review Manager program., Results: The systematic review included 28 studies (19 OS, 9 RCTs), whereas the meta-analysis included 4 RCTs. Results of the systematic review of OS revealed that higher A-RF consumption was associated with better sarcopenia outcomes. Results of the RCTs meta-analysis indicated that higher fruit/vegetable consumption, supplementation with magnesium, and vitamin E plus vitamin D and protein significantly reduced the time to complete 5 stands (mean difference; 95% CI; -1.11 s; 1.70, -0.51; p < 0.01). Additionally, including tea catechin supplementation significantly increased handgrip strength (1.02 kg; 0.60, 1.44; p < 0.01)., Conclusions: In sum, A-RF or antioxidant supplementation could be effective tools for sarcopenia, especially improving muscle strength and function. The best interventions according to the meta-analysis of the RCTs were supplementation of vitamin E in combination with vitamin D and protein, magnesium, tea catechins, and increasing fruit and vegetable consumption., Registration Number: PROSPERO (CRD42020183045)., Competing Interests: Declaration of competing interest No potential conflict of interest is reported by the authors., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: To assess the effects of enriched seafood sticks with postbiotic and bioactive compounds on CMD risk factors and the gut microbiota in abdominally obese individuals., Methods: Randomized, double-blind, parallel, placebo-controlled trial with abdominally obese individuals. Participants (n = 120) consumed 50 g/day of enriched seafood sticks containing SIAP: (10 10 colony forming units (CFUs) of heat-inactivated B. animalis subsp. lactis CECT8145, 370 mg/day omega 3 and 1.7 g/day inulin), or 50 g/day of placebo seafood sticks for 12 weeks. At 12 weeks, an acute single-dose study of 4 h was performed., Results: Sustained SIAP2 consumption significantly decreased the insulin by - 5.25 mg/dL and HOMA-IR (homeostatic Model Assessment of Insulin Resistance) by - 1.33. In women, SIAP2 consumption significantly decreased the pulse pressure (PP) by - 4.69 mmHg. Gut microbiota analysis showed a negative association between glycemic parameter reduction and Alistipes finegoldii and Ruminococcaceae, and between PP reduction and Prevotella 9-ASV0283 and Christensenellaceae. In the acute single dose-study 4-h, SIAP2 consumption produced a lower increase in the postprandial circulating triglyceride levels [23.9 (7.03) mg/dL (mean [standard error])] than the observed with placebo [49.0 (9.52)] mg/dL., Conclusion: In abdominally obese individuals, enriched seafood sticks induce a potential protection against type 2 diabetes development by the reduction in the insulin and HOMA-IR; and in cardiovascular disease, in women, by the PP reduction. These effects are accompanied by partial changes in the gut microbiota composition. The enriched seafood sticks reduce the atherogenic triglyceride postprandial concentrations. Our results support the use of enriched seafood sticks as a complementary strategy in the management of CMD risk factors. REGISTRATION NUMBER OF CLINICAL TRIAL: ( www., Clinicaltrials: gov ): NCT03630588 (August 15, 2018)., (© 2022. The Author(s).)

The present study aimed to evaluate the metabolism and bioavailability of anthocyanins (ACN) and other phenolics from red-fleshed apple (RFA) and to define the intake biomarkers compared to common white-fleshed apple (WFA). Acute and sustained (6-week) interventions were combined in a randomized, controlled and parallel study with 121 hypercholesterolemic subjects. Another arm consuming ACN-rich infusion from aronia fruit (ARO) provided matched content and profile of ACN. Plasma, urine and faeces samples were analyzed using UPLC-MS/MS. Results showed higher bioavailability of ACN after ARO compared to RFA, showing a clear apple matrix effect. The dihydrochalcone phloretin-2'-O-glucuronide was the most discriminant intake biomarker of both apples. The urinary peonidin-3-O-galactoside was a good biomarker after both ARO and RFA intakes, whereas peonidin-O-arabinoside was reported to be specific from ARO. The elucidation of the phenolic metabolism and the selection of intake biomarkers is a promising approach to relate phenolic compounds and human health., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Hesperidin is a flavanone abundantly found in citrus fruits for which health beneficial effects have been reported. However, hesperidin shows a low bioavailability among individuals. The aim of this study was to evaluate the effects of the micronization process and 2R- and 2S-hesperidin diastereoisomers ratio on hesperidin bioavailability. In a first phase, thirty healthy individuals consumed 500 mL of orange juice with 345 mg of hesperidin, and the levels of hesperidin metabolites excreted in urine were determined. In the second phase, fifteen individuals with intermediate hesperidin metabolite levels excreted in urine were randomized in a crossover, postprandial and double-blind intervention study. Participants consumed 500 mg of the hesperidin-supplemented Hesperidin epimeric mixture (HEM), the micronized Hesperidin epimeric mixture (MHEM) and micronized 2S-Hesperidin (M2SH) in each study visit with 1 week of washout. Hesperidin metabolites and catabolites were determined in blood and urine obtained at different timepoints over a 24 h period. The bioavailability-relative urinary hesperidin excretion (% of hesperidin ingested)-of M2SH (70 ± 14%) formed mainly by 2S-diastereoisomer was significantly higher than the bioavailability of the MHEM (55 ± 15%) and HEM (43 ± 8.0%), which consisted of a mixture of both hesperidin diastereoisomers. Relative urinary excretion of hesperidin metabolites for MHEM (9.2 ± 1.6%) was significantly higher compared to the HEM (5.2 ± 0.81%) and M2SH (3.6 ± 1.0%). In conclusion, the bioavailability of 2S-hesperidin extract was higher compared to the standard mixture of 2S-/2R-hesperidin extract due to a greater formation of hesperidin catabolites. Furthermore, the micronization process increased hesperidin bioavailability.

Anthocyanins (ACNs) are phenolic compounds present in foods and have undefined health benefits. The present umbrella review aimed to analyze the effects of ACNs on multiple aspects of human health (from systematic reviews and meta-analyses [SRMs] of randomized controlled trials [RCTs]), and the associations of ACNs with the risk of various diseases (from SRMs of observational studies [OSs]). Following the PRISMA methodology, the PubMed, SCOPUS, and Cochrane databases were searched up to November 1, 2020 for OS-SRMs and RCT-SRMs that examined the effects of ACNs on health. The risk of bias of RCT-SRMs was assessed using the AMSTAR 2, and that of OS-SRMs was assessed using the Joanna Briggs Institute methodology. Based on 5 OS-SRMs (57 studies and 2 134 336 participants), ACNs of various sources were significantly associated with a reduction in the risks of hypertension and type 2 diabetes mellitus. According to 8 RCT-SRMs (139 interventions and >4984 participants), ACNs improved plasmatic lipids, glucose metabolism, and endothelial function, without affecting blood pressure. No associations between ACNs and breast or gastric cancer risks were found. ACN intake opens new pathways for the management of glucose metabolism, the plasmatic lipid profile, and the improvement of endothelial function in humans., (© The Author(s) 2021. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The development and the evaluation of the Healthy Meals web app designed for professionals from different disciplines related to food, aimed to assess the nutritional and food allergen content of restaurant meals, was described., Methods: App evaluation concerned: (1) usability, scored on a 7-point scale by 6 restaurateurs and 10 nutritionists through the Computer System Usability Questionnaire; (2) quality, scored on a 5-point scale by 10 nutritionists through the Mobile App Rating Scale; (3) validation, by two nutritionists through differences in entered nutrient contents. Ratings reliability was assessed by the interclass correlation coefficient., Results: Users agreed with the web app usability (mean 5.6/7 points, SD 0.9), with moderate reliability among ratings (interclass correlation coefficient = 0.57; 95% CI, 0.18 to 0.82). The web app showed good objective quality (mean 4.0/5 points, SD 0.4), with excellent reliability among nutritionists (interclass correlation coefficient = 0.91; 95% CI, 0.85 to 0.96). For web app validation, no significant differences were observed between the two nutritionists' data, with excellent reliability (interclass correlation coefficient = 0.98; 95% CI, 0.97 to 0.99). App data entry was identified as a point to improve., Conclusions: The Healthy Meals web app designed for professionals related to food, such as restaurateurs, demonstrated to be usable, of good quality and valid for dishes nutritional assessment and food allergen identification. Points to improve were identified, while app effectiveness should be tested in trials., (© The Author(s) 2022.)

Background & Aims: Whether bioactive lysophospholipids (lyso-PLs) and trimethylamine-N-oxide (TMAO) serve as non-invasive biomarkers in early human hypercholesterolemia (HC) is unknown. This study aimed to assess whether serum lyso-PLs and plasma TMAO may be suitable susceptibility/risk biomarkers of HC in humans. Secondarily, we aimed to evaluate the relationships between targeted metabolites, diet composition and circulating liver transaminases, and verify these results in hamsters., Methods: A targeted metabolomics and lipidomics approach determined plasma TMAO and serum lysophosphatidylcholines (lyso-PCs) and lysophosphatidylethanolamines (lyso-PEs) in low (L-LDL-c) and moderate to high (MH-LDL-c) LDL-cholesterol subjects. Additionally, the relationships between targeted metabolites, liver transaminases and diet, particularly fatty acid intake, were tested. In parallel, plasma and liver lyso-PL profiles were studied in 16 hamsters fed a moderate high-fat (HFD) or low-fat (LFD) diet for 30 days., Results: Predictive models identified lyso-PC15:0 and lyso-PE18:2 as the most discriminant lyso-PLs among groups. In MH-LDL-c (n = 48), LDL-cholesterol and saturated FAs were positively associated with lyso-PC15:0, whereas in L-LDL-c (n = 70), LDL-cholesterol and polyunsaturated fatty acids (PUFAs) were negatively and positively related to lyso-PE18:2, respectively. Interestingly, in MH-LDL-c, the lower lyso-PE 18:2 concentrations were indicative of higher LDL-cholesterol levels. Intrahepatic accumulation of lyso-PLs-containing essential n-6 PUFAs, including lyso-PE18:2, were higher in HFD-fed hamsters than LFD-fed hamsters., Conclusions: Overall, results revealed a possible hepatic adaptive mechanism to counteract diet-induced steatosis in animal and hypercholesterolemia progression in humans. In particular, low serum lyso-PE18:2 suggests a suitable susceptibility/risk biomarker of HC in humans., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The consumption of aged black garlic (ABG) has been related to improvements in several cardiovascular disease (CVD) risk factors. However, the extent of the beneficial effects depends on the garlic aging process and the amount and type of chemical compounds accumulated. The main objective of this study was to assess the effect of daily intake of a well-characterized ABG extract with a standardized S-allyl-L-cysteine (SAC) yield in combination with dietary recommendations regarding CVD risk factors in individuals with moderate hypercholesterolemia. Sixty-seven hypercholesterolemic individuals with low-density lipoprotein cholesterol levels ≥115 mg/dL were randomized in a crossover, double-blind, sustained, and controlled intervention study. The participants consumed 250 mg (1.25 mg SAC)/tablet/day ABG or a placebo for 6 weeks, with 3 weeks of washout. Blood and pulse pressure and other CVD risk biomarkers were determined at the beginning and end of each intervention. At 6 weeks, ABG extract reduced diastolic blood pressure (DBP) (mean (95% CI) −5.85 (−10.5; −1.3) mm Hg) compared to the placebo, particularly in men with a DBP > 75 mm Hg. The consumption of an improved ABG extract with 1.25 mg of SAC decreased DBP, particularly in men with moderate hypercholesterolemia. The potential beneficial effects of ABG may contribute to obtaining an optimal DBP.

Scope: Hesperidin exerts cardiovascular beneficial effects, but its mechanisms of action remain undefined. In a previous study we demonstrated that a single dose and a 12-week treatment of hesperidin decreased systolic blood pressure. The aim of this study was to ascertain the action mechanisms of hesperidin consumption in subjects with elevated blood pressure or with stage 1 hypertension, by determining their transcriptomic profile after a single dose or a 12-week treatment., Methods and Results: For transcriptomic analysis, peripheral blood mononuclear cells were obtained from 37 subjects with elevated blood pressure and stage 1 hypertension from CITRUS study who were randomized to receive for 12 weeks: control drink (CD; n = 11), OJ (containing 345 mg of hesperidin; n = 15) or EOJ (containing 600 mg of hesperidin; n = 11). Before starting the 12-weeks treatment, a single dose study with a 6 h of follow-up in each group was performed. After the single dose consumption, EOJ versus OJ, downregulated DHRS9 gene which is related with insulin resistance. Compared to CD, 12-week treatment of EOJ downregulated 6 proinflammatory genes while after OJ consumption only 1 proinflammatory gene was downregulated. Moreover, 12-week treatment of EOJ versus OJ, downregulated acute coronary syndrome gene related (SELENBP1)., Conclusion: A single dose consumption of EOJ could protect from insulin resistance. Moreover, EOJ decrease the expression of proinflammatory genes after 12-week treatment providing a possible mechanism of action on inflammation pathway., Competing Interests: Conflict of interest The authors declare that they have not conflicts of interest with the content of this article., (Copyright © 2021. Published by Elsevier Ltd.)

Scope: The aim of the present work is to determine new biomarkers of the biological effects of hesperidin in orange juice (OJ) applying a non-targeted metabolomics approach validated by targeted metabolomics analyses of compliance biomarkers., Methods and Results: Plasma/serum and urine targeted (HPLC-MS/MS) and untargeted ( 1 H-NMR) metabolomics signatures are explored in a subsample with pre- and stage-1 hypertension subjects of the CITRUS study (N = 159). Volunteers received 500 mL day -1 of control drink, OJ, or hesperidin-enriched OJ (EOJ) for 12-weeks. A 6-h postprandrial study is performed at baseline. Targeted analyses reveals plasma and urine hesperetin 7-O-β-d-glucuronide as the only metabolite differing between OJ and EOJ groups after 12-weeks consumption, and in urine is correlated with a decreased systolic blood pressure level. The non-targeted approach shows that after single dose and 12-weeks consumption of OJ and EOJ change several metabolites related with an anti-inflammatory and antioxidant actions, lower blood pressure levels and uremic toxins., Conclusions: Hesperetin 7-O-β-d-glucuronide can be a candidate marker for distinguishing between the consumption of different hesperidin doses at 12-weeks consumption as well as a potential agent mediating blood pressure reduction. Moreover, changes in different endogenous metabolites can explain the mechanisms of action and the biological effects of hesperidin consumption., (© 2021 Wiley-VCH GmbH.)

The purpose of the present study was to compare the relative absorption of a new powder presentation of silicon (Si) as orthosilicic acid with maltodextrin (Orgono Powder) compared to usual Si liquid presentations as orthosilicic acid with Equisetum arvense and Rosmarinus officinalis (G5 Siliplant) and orthosilicic acid with aloe vera (G7 Aloe). All dietary supplements were administered at the same Si oral dose (21.6 mg) in a randomized, double-blind, crossover post-prandial study conducted in 5 healthy men. Urine was collected at baseline and over the 6-h post-dose period in 2 separate 3-h collections for the analysis of Si concentration, which was conducted by inductively coupled plasma optical emission spectrometry as the gold standard method. No significant differences in total urinary Si excretion were found after the intake of these 3 dietary supplements; 34.6%, 32.4% and 27.2% of the ingested Si from G7 Aloe, G5 Siliplant and Orgono Powder, respectively, was excreted in urine over the 6-h follow-up period. The 3 different oral Si formulations tested, in powder and liquid presentations, provide highly bioavailable Si and present an equivalent relative absorption in healthy humans., (© 2021. The Author(s).)

Restaurant meal consumption has increased substantially, but the ability of restaurants to adhere to guidelines for the Mediterranean diet, healthiness and food allergen management is a challenge. This cross-sectional study aims to assess the Mediterranean diet adherence, healthiness, nutritional quality and food allergen management of meals at restaurants in the Tarragona province (Catalonia, Spain). Primary outcomes included adherence to criteria for the Mediterranean diet (AMed) and gluten management (SMAP), nutritional quality of dishes indicated by a green traffic light rating, meal nutrient content and allergen-free options. Secondary outcomes included restaurant staff knowledge about the Mediterranean diet and food allergens. Forty-four restaurants and 297 dishes were analysed. The restaurants fulfilled an average (mean ± SD) of 5.1 ± 1.6 of 9 compulsory AMed criteria and 12.9 ± 2.8 of 18 SMAP criteria. Dishes were mainly rated green for sugar ( n = 178/297; 59.9%) but not for energy ( n = 23/297; 7.7%) or total fat ( n = 18/297; 6.1%). Waiters and cooks received passing scores for food allergen knowledge (5.8 ± 1.7 and 5.5 ± 1.5 out of 10 points, respectively). Restaurants partially met the AMed and SMAP criteria. Increasing fibre and decreasing saturated fat content are necessary to improve consumers' adherence to healthy diets. For restaurant staff, training courses should be considered to improve their food allergen management.

We aimed to differentiate gut microbiota composition of overweight/obese and lean subjects and to determine its association with clinical variables and dietary intake. A cross-sectional study was performed with 96 overweight/obese subjects and 32 lean subjects. Anthropometric parameters were positively associated with Collinsella aerofaciens , Dorea formicigenerans and Dorea longicatena , which had higher abundance the overweight/obese subjects. Moreover, different genera of Lachnospiraceae were negatively associated with body fat, LDL and total cholesterol. Saturated fatty acids (SFAs) were negatively associated with the genus Intestinimonas , a biomarker of the overweight/obese group, whereas SFAs were positively associated with Roseburia , a biomarker for the lean group. In conclusion, Dorea formicigenerans , Dorea longicatena and Collinsella aerofaciens could be considered obesity biomarkers, Lachnospiraceae is associated with lipid cardiovascular risk factors. SFAs exhibited opposite association profiles with butyrate-producing bacteria depending on the BMI. Thus, the relationship between diet and microbiota opens new tools for the management of obesity.

In the present study, potential associations between dietary phenolic compounds (PCs), gut microbiota composition and targeted faecal metabolites were identified in a cross-sectional study including grade 1 hypertensive (HT) and normotensive (NT) subjects. We performed comprehensive quantification of PC intake, together with 16S rRNA gene sequencing of the gut microbiota, and faecal and plasma short-chain fatty acids (SCFAs) determination. The results showed multiple-way relationships between PCs from several plant-based foods and 25 bacterial taxa previously defined as discriminant biomarkers among groups. Remarkably, coffee PCs were positively associated with systolic and diastolic blood pressure, faecal SCFAs, Bacteroides plebeius and Bacteroides coprocola in HT and negatively associated with Faecalibacterium prausnitzii and Christensenellaceae R-7 in NT. Olive fruit PCs were positively associated with Ruminococcaceae UCG-010, Christensenellaceae R-7 and plasma SCFAs in NT. These interplays with discriminant bacterial taxa in HT and NT subjects highlight the potential role of specific PCs as gut microbiome modulators in either the pathogenesis or prevention of hypertension., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Scope: The lipidomic analysis of high-density lipoprotein (HDL) could be useful to identify new biomarkers of HDL function., Methods and Results: A randomized, controlled, double-blind, crossover trial (33 hypercholesterolaemic subjects) is performed with a control virgin olive oil (VOO), VOO enriched with its own phenolic compounds (FVOO), or VOO enriched with additional phenolic compounds from thyme (FVOOT) for 3 weeks. HDL lipidomic analyses are performed using the Lipidyzer platform. VOO and FVOO intake increase monounsaturated-fatty acids (FAs) and decrease saturated and polyunsaturated FAs in triacylglyceride (TAG) species, among others species. In contrast, FVOOT intake does not induce these FAs changes. The decrease in TAG52:3(FA16:0) after VOO intake and the decrease in TAG52:5(FA18:2) after FVOO intake are inversely associated with changes in HDL resistance to oxidation. After FVOO intake, the decrease in TAG54:6(FA18:2) in HDL is inversely associated with changes in HDL cholesterol efflux capacity., Conclusion: VOO and FVOO consumption has an impact on the HDL lipidome, in particular TAG species. Although TAGs are minor components of HDL mass, the observed changes in TAG modulated HDL functionality towards a cardioprotective mode. The assessment of the HDL lipidome is a valuable approach to identify and characterize new biomarkers of HDL function., (© 2021 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH.)

The present study aims to investigate the metabolic fate and the cardiometabolic effects of phenolic compounds provided by a red-fleshed apple variety biofortified in anthocyanins (ACN). Wistar rats are fed with high-fat diet (HFD) to induce hypercholesterolemia and supplemented with red-fleshed apple (HFD+R), white-fleshed apple (HFD+W), or an ACN-rich infusion from aronia fruit (HFD+A) providing matched content and profile of ACN. Plasma biochemical parameters, histological analysis, and phenol biological metabolites are determined. Plasma, urine, and feces show a significant increase of ACN metabolites after HFD+R and HFD+A, while flavan-3-ols are significantly increased after HFD+W and dihydrochalcones derivatives increased after both apples supplementation. A cardioprotective effect is observed after both apples and aronia infusion supplementation in the reduction of aortic thickness. The kidney function is improved after all supplementations and a decrease in insulin plasma concentration after both apples supplementation (HFD+R and HFD+W) is also observed. The findings support that ACN without apple matrix can induce cardioprotective effects. ACN or flavan-3-ols, together with dihydrochalcones, compose a phenolic phytocomplex in red- and white-fleshed apples, respectively, which can act synergistically in the attenuation of cardiovascular outcomes in hypercholesterolemic rats., (© 2021 Wiley-VCH GmbH.)

Out-of-home eating is increasing, but evidence about its healthiness is limited. The present systematic review and meta-analysis aimed to elucidate the effectiveness of full-service restaurant and canteen-based interventions in increasing the dietary intake, food availability, and food purchase of healthy meals. Studies from 2000-2020 were searched in Medline, Scopus, and Cochrane Library using the PRISMA checklist. A total of 35 randomized controlled trials (RCTs) and 6 non-RCTs were included in the systematic review and analyzed by outcome, intervention strategies, and settings (school, community, workplace). The meta-analysis included 16 RCTs (excluding non-RCTs for higher quality). For dietary intake, the included RCTs increased healthy foods (+0.20 servings/day; 0.12 to 0.29; p < 0.001) and decreased fat intake (-9.90 g/day; -12.61 to -7.19; p < 0.001), favoring the intervention group. For food availability, intervention schools reduced the risk of offering unhealthy menu items by 47% (RR 0.53; 0.34 to 0.85; p = 0.008). For food purchases, a systematic review showed that interventions could be partially effective in improving healthy foods. Lastly, restaurant- and canteen-based interventions improved the dietary intake of healthy foods, reduced fat intake, and increased the availability of healthy menus, mainly in schools. Higher-quality RCTs are needed to strengthen the results. Moreover, from our results, intervention strategy recommendations are provided.

Purpose: To assess the sustained and acute effects, as well as the influence of sustained consumption on the acute effects, of orange juice (OJ) with a natural hesperidin content and hesperidin-enriched OJ (EOJ) on blood (BP) and pulse (PP) pressures in pre- and stage-1 hypertensive individuals., Methods: In a randomized, parallel, double-blind, placebo-controlled trial, participants (n = 159) received 500 mL/day of control drink, OJ, or EOJ for 12 weeks. Two dose-response studies were performed at baseline and after 12 weeks., Results: A single EOJ dose (500 mL) reduced systolic BP (SBP) and PP, with greater changes after sustained treatment where a decrease in diastolic BP (DBP) also occurred (P < 0.05). SBP and PP decreased in a dose-dependent manner relative to the hesperidin content of the beverages throughout the 12 weeks (P < 0.05). OJ and EOJ decreased homocysteine levels at 12 weeks versus the control drink (P < 0.05). After 12 weeks of EOJ consumption, four genes related to hypertension (PTX3, NLRP3, NPSR1 and NAMPT) were differentially expressed in peripheral blood mononuclear cells (P < 0.05)., Conclusion: Hesperidin in OJ reduces SBP and PP after sustained consumption, and after a single dose, the chronic consumption of EOJ enhances its postprandial effect. Decreases in systemic and transcriptomic biomarkers were concomitant with BP and PP changes. EOJ could be a useful co-adjuvant tool for BP and PP management in pre- and stage-1 hypertensive individuals.

Turmeric extracts (TEs) have been shown to be suitable as a pain treatment for human joint arthritis. In a pilot, randomized clinical trial, 68 individuals with mild/moderate knee joint pain (KJP) consumed a new formulation of water-soluble TEs and insoluble curcuminoids (B-Turmactive ® ) or brewer's yeast as a placebo for 1 week. Our hypothesis was that B-Turmactive would have a short-term analgesic effect on KJP measured by the self-reported Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). After 3 days and 1 week, both treatments reduced pain when walking on a flat surface ( P  < .01), going up or down stairs ( P  < .001), and sitting or lying ( P  < .05), but only B-Turmactive reduced pain at night while in bed and in an upright standing position ( P  < .01). Concerning global KJP, it was reduced by both treatments after 3 days and 1 week of the intervention ( P  < .001), being less with B-Turmactive after 1 week ( P  = .012 vs. 3 weeks). Although no intertreatment differences were observed, only B-Turmactive decreased high-sensitivity C-reactive protein levels ( P  = .045) at 1 week, which indicates a prompt analgesic effect mediated by a decrease in inflammatory status.

Background & Aims: The integrity of the intestinal barrier in the diseased is key to prevent further complications and disease such as sepsis and death, whereas, the role of food bioactive molecules (i. e. phenolic compounds (PCs) on the intestinal barrier, is still unknown. The current aim was to explore the benefits of the oral PC administration on the intestinal barrier integrity in animals., Methods: The effects of PCs on the intestinal barrier integrity in in vivo animal models of intestinal inflammation were assessed up-to August 2020 from the PubMed, SCOPUS, and Cochrane Library databases under the PRISMA methodology. The risk of bias was assessed from ARRAY and SCYRCLE tools., Results: From 1241 articles, 14 studies were included. In animals, oral resveratrol (n = 6) improves the intestinal barrier integrity and reduces intestinal damage. Additionally, grape seed extract (n = 2), curcumin (n = 1), genistein (n = 1), chlorogenic acid (n = 1), grape pomace (n = 1), olive leaf (n = 1) or cranberry extract (n = 1) improve the intestinal barrier integrity downregulating various inflammatory molecules (TNF-α, and other interleukins), and increasing the antioxidant enzymes in animals. Furthermore, resveratrol, quercetin, epigallocatechin, and other PCs improve the epithelial barrier integrity and pro-inflammatory molecule expression in the intestinal epithelia., Conclusions: The oral PC administration in animals improves the intestinal barrier integrity and function from three main mechanisms: 1) The reduction of pro-inflammatory molecules, 2) the improvement in tight-junction protein expression, and 3) the improvement of the antioxidant intracellular activity suggesting the potential use of PCs in the management of intestinal injury in humans, particularly for resveratrol, the most studied PC., Competing Interests: Conflict of interest The authors have declared no conflicts of interest. Complete Declaration of Interest forms for each author has been uploaded at the time of manuscript submission., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Probiotic foods, including fermented dairy (FD) products such as yogurt and cheese, naturally contain live microorganisms, but the relationship between the consumption of probiotic foods and health is unclear. The aim of the present narrative review is to integrate the available information on the relationship between the most studied FD products, which are yogurt and cheese, and cardiometabolic risk factors obtained from meta-analysis, systematic reviews of prospective cohort studies (PCSs) and PCSs published up to 2 November 2019. Additionally, the effects identified by randomized controlled trials of less-studied FD products, such as kefir and kimchi, on cardiometabolic risk factors are provided. PCSs have shown that the consumption of cheese, despite its high saturated fat content, is not associated with expected hypercholesterolemia and an increased cardiovascular risk. PCSs have revealed that the total consumption of FD appears to be associated with a lower risk of developing stroke and cardiovascular disease. The consumption of yogurt seems to be associated with a lower risk of developing type 2 diabetes. There is a lack of sufficient evidence of a protective relationship between FD or cheese consumption and metabolic syndrome. Moreover, the association of FD, cheese and yogurt with hypertension needs further evidence. In conclusion, the intake of fermented foods containing probiotics, particularly yogurt and cheese (of an undetermined type), opens up new opportunities for the management of cardiometabolic risk factors.

Background: Food allergies and intolerances are increasing worldwide, and mobile phone apps could be a promising tool for self-management of these issues., Objective: This study aimed to systemically search and assess food allergy or intolerance apps in app stores using the multidimensional Mobile App Rating Scale (MARS) to rate the objective and subjective quality and to identify critical points for future improvements., Methods: This systematic search identified apps through the keywords "food allergy," "food intolerance," and "allergens" in English, Spanish, and Italian in the Apple App Store (iOS) and Google Play Store (Android). The inclusion criteria were a user star rating of ≥3 (of 5 stars) to limit the selection to the most highly rated apps; ≥1000 reviews as an indicator of reliability; and the most recent update performed up to 2017. Then, the apps were divided according to their purpose (searching for allergen-free "food products," "restaurants," or recipes in "meal planners") and evaluated on a scale of 1 to 5 points using the MARS in terms of (1) app classification category with a descriptive aim; (2) app subjective and objective quality categories comprised of engagement, functionality, esthetics, and information sections (Medline was searched for eligible apps to check whether they had been tested in trials); and (3) an optional app-specific section. Furthermore, the output and input features were evaluated. Differences between MARS sections and between app purposes and correlations among MARS sections, star ratings, and numbers of reviews were evaluated., Results: Of the 1376 apps identified, 14 were included: 12 related to food allergies and intolerances that detect 2-16 food allergens and 2 related only to gluten intolerance. The mean (SD) MARS scores (maximum 5 points) were 3.8 (SD 0.4) for objective quality, highlighting whether any app had been tested in trials; 3.5 (SD 0.6) for subjective quality; and 3.6 (SD 0.7) for the app-specific section. Therefore, a rating ≥3 points indicated overall acceptable quality. From the between-section comparison, engagement (mean 3.5, SD 0.6) obtained significantly lower scores than functionality (mean 4.1, SD 0.6), esthetics (mean 4, SD 0.5), and information (mean 3.8, SD 0.4). However, when the apps were compared by purpose, critical points were identified: meal planner apps showed significantly higher engagement (mean 4.1, SD 0.4) than food product (mean 3.0, SD 0.6; P=.05) and restaurant (mean 3.2, SD 0.3; P=.02) apps., Conclusions: In this systematic search of food allergy or intolerance apps, acceptable MARS quality was identified, although the engagement section for food product and restaurant purpose apps should be improved and the included apps should be tested in trials. The critical points identified in this systematic search can help improve the innovativeness and applicability of future food allergy and intolerance apps., (©Floriana Mandracchia, Elisabet Llauradó, Lucia Tarro, Rosa Maria Valls, Rosa Solà. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 16.09.2020.)

Scope: We investigate the postprandial modulation of cardiovascular-related microRNAs elicited by extra virgin olive oil (EVOOs) containing different levels of their own polyphenols., Methods and Results: It is randomized, postprandial, parallel, double-blind study. Twelve healthy participants consumed 30 mL of EVOO containing low (L-EVOO; 250 mg total phenols kg -1 of oil), medium (M-EVOO; 500 mg total phenols kg -1 of oil), and high (H-EVOO; 750 mg total phenols kg -1 of oil) enriched EVOOs. Postprandial plasma microRNAs levels are analyzed by real-time quantitative PCR. The results show that L-EVOO intake is associated with decreased let-7e-5p and miR-328a-3p levels and increased miR-17-5p and miR-20a-5p, concentrations. M-EVOO decreases plasma let-7e-5p and increases miR-17-5p, miR-20a-5p, and miR-192-5p levels. Finally, H-EVOO decreases let-7e-5p, miR-10a-5p, miR-21-5p, and miR-26b-5p levels., Conclusion: During the postprandial state, the levels of let-7e-5p decrease with EVOO regardless of polyphenol content suggesting a general response to the fatty acid composition of EVOO or/and the presence of at least 250 mg polyphenol kg -1 olive oil. Moreover, the miR-17-92 cluster increases by low and medium polyphenol content suggesting a role in fatty acid metabolism and nutrient sensing. Thus, postprandial modulation of circulating microRNAs levels could be a potential mechanism for the cardiovascular benefits associated with EVOO intake., (© 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Fermented dairy foods (FDFs) and probiotics are promising tools for the prevention and management of cardiometabolic diseases (CMDs), respectively. The relation between the regular consumption of FDFs and CMD risk factors was assessed by prospective cohort studies (PCSs), and the effect of probiotic supplementation added into a dairy matrix on CMD parameters was evaluated by randomized controlled trials (RCTs). Moreover, the effects of probiotic supplementation added into a dairy matrix were compared with those administered in capsule/powder form. Twenty PCSs and 52 RCTs met the inclusion criteria for the systematic review and meta-analysis. In PCSs, fermented milk was associated with a 4% reduction in risk of stroke, ischemic heart disease, and cardiovascular mortality [RR (95% CI); 0.96 (0.94, 0.98)]; yogurt intake was associated with a risk reduction of 27% [RR (95% CI); 0.73 (0.70, 0.76)] for type 2 diabetes (T2D) and 20% [RR (95% CI); 0.80 (0.74, 0.87)] for metabolic syndrome development. In RCTs, probiotic supplementation added into dairy matrices produced a greater reduction in lipid biomarkers than when added into capsules/powder in hypercholesterolemic subjects, and probiotic supplementation by capsules/powder produced a greater reduction in T2D biomarkers than when added into dairy matrices in diabetic subjects. Both treatments (dairy matrix and capsules/powder) resulted in a significant reduction in anthropometric parameters in obese subjects. In summary, fermented milk consumption is associated with reduced cardiovascular risk, while yogurt intake is associated with a reduced risk of T2D and metabolic syndrome development in the general population. Furthermore, probiotic supplementation added into dairy matrices could be considered beneficial for lowering lipid concentrations and reducing anthropometric parameters. Additionally, probiotic capsule/powder supplementation could contribute to T2D management and reduce anthropometric parameters. However, these results should be interpreted with caution due to the heterogeneity of the studies and the different probiotic strains used in the studies. This trial is registered with PROSPERO (CRD42018091791) and the protocol can be accessed at http://www.crd.york.ac.uk/PROSPERO/display&#95;record.php?ID=CRD42018091791., (Copyright © The Author(s) 2020.)

Scope: Proteomics has provided new strategies to elucidate the mechanistic action of hesperidin, a flavonoid present in citrus fruits. Thus, the aim of the present study is to determine the effects of hesperidin supplementation (HS) on the proteomic profiles of heart and kidney tissue samples from healthy and metabolic syndrome (MS) rats., Methods and Results: 24 Sprague Dawley rats are randomized into four groups: healthy rats fed with a standard diet without HS, healthy rats administered with HS (100 mg kg -1 day -1 ), MS rats without HS, and MS rats administered with HS (100 mg kg -1 day -1 ) for eight weeks. Heart and kidney samples are obtained, and proteomic analysis is performed by mass spectrometry. Multivariate, univariate, and ingenuity pathways analyses are performed. Comparative and semiquantitative proteomic analyses of heart and kidney tissues reveal differential protein expression between MS rats with and without HS. The top diseases and functions implicated are related to the cardiovascular system, free radical scavenging, lipid metabolism, glucose metabolism, and renal and urological diseases., Conclusion: This study is the first to demonstrate the protective capacity of hesperidin to change to the proteomic profiles in relation to different cardiovascular risk biomarkers in the heart and kidney tissues of MS rats., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Hypertension is an independent and preventable risk factor for the development of cardiovascular diseases, however, little is known about the impact of gut microbiota composition in its development. We carried out comprehensive gut microbiota analysis and targeted metabolomics in a cross-sectional study of 29 non-treated hypertensive (HT) and 32 normotensive (NT) subjects. We determined fecal microbiota composition by 16S rRNA gene sequencing and bacterial functions by metagenomic analysis. The microbial metabolites analysed were short chain fatty acids (SCFA) both in plasma and feces, and trimethylamine N-oxide (TMAO) in plasma. The overall bacterial composition and diversity of bacterial community in the two groups were not significantly different. However, Ruminococcaceae NK4A214, Ruminococcaceae&#95;UCG-010, Christensenellaceae&#95;R-7, Faecalibacterium prausnitzii and Roseburia hominis were found to be significantly enriched in NT group, whereas, Bacteroides coprocola, Bacteroides plebeius and genera of Lachnospiraceae were increased in HT patients. We found a positive correlation between the HT-associated species and systolic and diastolic blood pressure after adjusted for measured confounders. SCFA showed antagonistic results in plasma and feces, detecting in HT subjects significant higher levels in feces and lower levels in plasma, which could indicate a less efficient SCFA absorption. Overall, our results present a disease classifier based on microbiota and bacterial metabolites to discriminate HT individuals from NT controls in a first disease grade prior to drug treatment.

Context: The cardioprotective effects of the flavonoid hesperidin, which is present in citrus products, are controversial and unclear. This systematic review was conducted in accordance with the PRISMA 2015 guidelines., Objective: To evaluate the current evidence from animal and human clinical studies and thus determine whether the consumption of hesperidin exerts beneficial effects on cardiovascular risk factors., Data Sources: PICOS (Population, Intervention, Comparison, Outcome, and Study Design) criteria defined the research question. Searches of the PubMed and Cochrane Plus databases were conducted and studies that met the inclusion criteria and were published in English in the last 15 years were included., Data Extraction: The first author, year of publication, study design, characteristics of animals and humans, intervention groups, dose of hesperidin, route of administration, duration of the intervention, cardiovascular risk biomarkers assessed, and results observed were extracted from the included articles., Results: A total of 12 animal studies and 11 randomized clinical trials met the inclusion criteria. In the animal studies, the glucose, total and LDL cholesterol, and triglyceride levels decreased with chronic flavonoid consumption. In the human studies, endothelial function improved with flavonoid consumption, whereas no conclusive results were observed for the other biomarkers., Conclusions: Animal studies have revealed that hesperidin and hesperetin consumption reduces glucose levels and various lipid profile parameters. However, a definitive conclusion cannot be drawn from the existing human clinical trials. Further research is needed to confirm whether the findings observed in animal models can also be observed in humans., Systematic Review Registration: Prospero registration number CRD42018088942., (© The Author(s) 2019. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The effects of probiotic Bifidobacterium animalis subsp. lactis CECT 8145 (Ba8145) and those of its heat-killed form (h-k Ba8145) on human anthropometric adiposity biomarkers are unknown., Objective: To assess the effect of Ba8145 and h-k Ba8145 ingestion on anthropometric adiposity biomarkers., Design: Randomized, parallel, double-blind, placebo-controlled trial with abdominally obese individuals. Participants (n = 135) consumed 1 capsule/day containing 10 10 colony forming unit (CFU) of Ba8145, 10 10 CFU of h-k Ba8145, or placebo (maltodextrin) for 3 months., Results: Ba8145 ingestion decreased waist circumference, waist circumference/height ratio, and Conicity index (P < 0.05) versus its baseline. Changes versus the placebo group reached significance (P < 0.05) after the h-k Ba8145 treatment. Ba8145 decreased the body mass index compared with baseline and placebo group (P < 0.05). The decrease in visceral fat area after Ba8145 treatments reached significance (P < 0.05) only after h-k Ba8145. When analyses by gender were performed, significance remained only for women. Diastolic blood pressure and HOMA index decreased (P < 0.05) after h-k Ba8145. Gut microbiome analyses showed an increase in Akkermansia spp. after Ba8145 treatment, particularly in the live form, which was inversely related to weight (P = 0.003)., Conclusions: In abdominally obese individuals, consumption of Ba8145, both as viable and mainly as heat-killed cells, improves anthropometric adiposity biomarkers, particularly in women. An increase in the gut Akkermansia genus appears as a possible mechanism involved. Our results support Ba8145 probiotic as a complementary strategy in obesity management.

A wide range of chronic diseases could be prevented through healthy lifestyle choices, such as consuming five portions of fruits and vegetables daily, although the majority of the adult population does not meet this recommendation. The use of mobile phone applications for health purposes has greatly increased; these applications guide users in real time through various phases of behavioural change. This review aimed to assess the potential of self-monitoring mobile phone health (mHealth) applications to increase fruit and vegetable intake. PubMed and Web of Science were used to conduct this systematized review, and the inclusion criteria were: randomized controlled trials evaluating mobile phone applications focused on increasing fruit and/or vegetable intake as a primary or secondary outcome performed from 2008 to 2018. Eight studies were included in the final assessment. The interventions described in six of these studies were effective in increasing fruit and/or vegetable intake. Targeting stratified populations and using long-lasting interventions were identified as key aspects that could influence the effectiveness of these interventions. In conclusion, evidence shows the effectiveness of mHealth application interventions to increase fruit and vegetable consumption. Further research is needed to design effective interventions and to determine their efficacy over the long term.

Scope: The main findings of the "Virgin Olive Oil and HDL Functionality" (VOHF) study and other related studies on the effect of phenol-enriched virgin olive oil (VOO) supplementation on cardiovascular disease are integrated in the present work., Methods and Results: VOHF assessed whether VOOs, enriched with their own phenolic compounds (FVOO) or with those from thyme (FVOOT), improve quantity and functionality of HDL. In this randomized, double-blind, crossover, and controlled trial, 33 hypercholesterolemic subjects received a control VOO (80 mg kg -1 ), FVOO (500 mg kg -1 ), and FVOOT (500 mg kg -1 ; 1:1) for 3 weeks. Both functional VOOs promoted cardioprotective changes, modulating HDL proteome, increasing fat-soluble antioxidants, improving HDL subclasses distribution, reducing the lipoprotein insulin resistance index, increasing endogenous antioxidant enzymes, protecting DNA from oxidation, ameliorating endothelial function, and increasing fecal microbial metabolic activity. Additional cardioprotective benefits were observed according to phenol source and content in the phenol-enriched VOOs. These insights support the beneficial effects of OO and PC from different sources., Conclusion: Novel therapeutic strategies should increase HDL-cholesterol levels and enhance HDL functionality. The tailoring of phenol-enriched VOOs is an interesting and useful strategy for enhancing the functional quality of HDL, and thus, it can be used as a complementary tool for the management of hypercholesterolemic individuals., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Purpose: To determine the effects of the intake of low-fat yoghurt supplemented with rooster comb extract (RCE) on muscle strength., Methods and Results: 148 subjects, with mild knee pain, participated in a randomized, placebo-controlled, double-blind, and parallel study. Muscle strength, knee effusion, and pain perception were measured. C2C12 myoblasts were used to elucidate the mechanisms of action involved. RCE improved total work and mean power in men, and also peak torque in extension by 10%. RCE reduced synovial effusion by 11.8% and pain perception by 24.6%. Both RCE and HA increased myoblast proliferation by 29%, while RCE reduced myoblast differentiation by 36.2%, suggesting a beneficial role of RCE in muscle regeneration., Conclusions: Low-fat yoghurt supplemented with RCE improved muscle strength. This effect is partially explained by muscle regeneration enhancement, reduced synovial effusion, and reduced pain perception, which could exert a beneficial clinical impact on men affected by mild knee pain.

Scope: Cholesterol efflux capacity of HDL (CEC) is inversely associated with cardiovascular risk. HDL composition, fluidity, oxidation, and size are related with CEC. We aimed to assess which HDL parameters were CEC determinants after virgin olive oil (VOO) ingestion., Methods and Results: Post-hoc analyses from the VOHF study, a crossover intervention with three types of VOO. We assessed the relationship of 3-week changes in HDL-related variables after intervention periods with independence of the type of VOO. After univariate analyses, mixed linear models were fitted with variables related with CEC and fluidity. Fluidity and Apolipoprotein (Apo)A-I content in HDL was directly associated, and HDL oxidative status inversely, with CEC. A reduction in free cholesterol, an increase in triglycerides in HDL, and a decrease in small HDL particle number or an increase in HDL mean size, were associated to HDL fluidity., Conclusions: HDL fluidity, ApoA-I concentration, and oxidative status are major determinants for CEC after VOO. The impact on CEC of changes in free cholesterol and triglycerides in HDL, and those of small HDL or HDL mean size, could be mechanistically linked through HDL fluidity. Our work points out novel therapeutic targets to improve HDL functionality in humans through nutritional or pharmacological interventions., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Scope: Low paraoxonase (PON)1 activities, and high PON1 and low PON3 protein levels are characteristic of cardiovascular disease. Our aim was to assess short- and long-term effects of virgin olive oils (VOO), enriched with their own phenolic compounds (PC; FVOO) or with them plus complementary PC from thyme (FVOOT), on PON-related variables and the mechanisms involved., Methods and Results: Two randomized, controlled, double-blind, and crossover interventions were conducted. In an acute intake study, participants ingested three FVOOs differing in PC content. In a sustained intake study, participants ingested a control VOO and two different FVOOs with the same PC content but differing in PC source. Acute and sustained intake of VOO and FVOO decreased PON1 protein and increased PON1-associated specific activities, while FVOOT yielded opposite results. PON3 protein levels increased only after sustained consumption of VOO. Mechanistic studies performed in rat livers showed that intake of isolated PC from VOO and from thyme modulate mitogen-activated protein kinases and peroxisome proliferator-activated receptors regulating PON synthesis, while a combination of these PCs cancels such regulation., Conclusion: This study reveals that the intake of phenol-enriched FVOOs modulates oxidative balance by modifying PON-related variables according to PC content and source, and this modulation can be perceived as beneficial., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Dietary phenolic compounds (PCs) have been receiving interest for their presumed roles in disease prevention. However, there is a lack of studies on the underlying molecular mechanisms. In this regard, in vitrometabolomic approaches are suitable for the investigation of the molecular changes in response to PC exposure. Up to date, the biological effects of PCs have only been examined for PCs from rosemary (Rosmarinus officinalis), olive oil, and resveratrol using cell-based metabolomic approach, although transcriptomic and/or proteomic studies have also been conducted in the same in vitro cell experiment in some cases. Our integral analysis of the reviewed studies suggest that PCs may be involved not only in basic cellular processes or macro- and micro-nutrient metabolism, but also in specific metabolic pathways that have been thoroughly investigated. These modulated pathways could have a clinical impact on neurodegenerative diseases, type 2 diabetes, cancer, and cardiovascular diseases. In conclusion, the in vitro metabolomic approaches provide additional information of the molecular mechanisms involved in disease risk reduction of dietary PCs. In order to elucidate the mechanisms of action of PCs, more metabolomic cell-based studies are needed and testing the physiological conjugated forms of PCs in these cell systems could be of special interest., (Copyright © 2017 Beijing Institute of Genomics, Chinese Academy of Sciences and Genetics Society of China. Production and hosting by Elsevier B.V. All rights reserved.)

The association between the consumption of seafood and its benefits on cardiovascular (CVD) risk can be challenged by its heavy metal (HM) content. This study aimed to explore the association of seafood consumption and its estimated HM contents with the lipid profile and lipid oxidation biomarkers in adults from a Spanish Mediterranean area who do not present risk factors for CVD. In this cross-sectional study, the clinical history, three-day dietary record, lipid profile (LDLc, HDLc, APOB/A, and triglyceride levels), plasma oxidised LDL (oxLDL) and 8-isoprostane levels of 81 adults without risk factors for CVD [43% men, with a mean age of 43.6 years (95%CI: 40.1-47.1)] were assessed. The HM [arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb)] contents of seafood were estimated according to data from analyses of marine species in the same Mediterranean area. Moderate adherence to the Mediterranean diet (score: 4.6 of 9) with a mean seafood consumption of 74.9g/day (95%CI: 59.9-89.9), including 22.7g of shellfish per day (95%CI: 13.5-31.9), was observed. The estimated HM contents were lower than the provisional tolerable weekly intakes (PTWIs): 21.12µg/kg/week As, 0.57µg/kg/week InAs, 0.15µg/kg/week Cd, 1.11µg/kg/week Hg and 0.28µg/kg/week Pb. After adjusting by confounder variables, an increase in shellfish consumption was associated with increases in the levels of LDLc (P=0.013), non-HDLc (P=0.015), APOB/A (P=0.02) and plasma oxLDL (P=0.002). Moreover, an increase in the estimated As and Hg levels in shellfish was associated with an increase in LDLc (P=0.015 and P=0.018, respectively), non-HDLc (P<0.008 and P<0.008, respectively), APOB/A ratio (P=0.008 and P=0.009, respectively), and oxLDL (P≤0.001 and P≤0.001, respectively) levels. In conclusion, in adults without risk factors for CVD, increasing shellfish consumption, even by a moderate amount, could favour a pro-atherogenic lipid profile and a higher level of oxidised LDL. These associations are likely influenced by the estimated exposure to As and Hg from shellfish despite these values are lower than the PTWIs., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Oligopin ۚ (OP) is a quantified extract from French Maritime Pine bark (FMPB) with low molecular weight procyanidins. The cardioprotective effects of OP need to be tested in human clinical intervention trials with an appropriate design., Purpose: The aim of the present study was to assess the effect of subchronic consumption of OP on cardiovascular disease risk factors such as lipid profile, systolic blood pressure (BP) and oxidized-Low Density Lipoprotein (ox-LDL) in stage-1-hypertensive subjects., Methods: Between February 14 and May 31, 2014, eligible subjects were recruited from the outpatient clinics of Hospital Universitari Sant Joan (Reus, Spain). A total of 24 participants (mean age ± DS; 57.36 ± 11.25; 17 men) with stage-1-hypertension who were not receiving BP-lowering medication and LDL cholesterol < 4.88 mmol/l were randomized in a double-blind, placebo-controlled, crossover study. The subjects received 2 capsules/day with 75 mg of OP or placebo for 5-weeks., Results: At 5-weeks, compared to the placebo, OP raised High Density Lipoprotein-cholesterol (HDL-c) by 14.06% (p = 0.012) and apolipoprotein A-1 by 8.12% (p = 0.038) and reduced the ratio of apolipoprotein B-100/A-1 by 10.26% (p = 0.046). Moreover, at 5-weeks, compared to the baseline, OP reduced the systolic BP by 6.36 mmHg (p = 0.014), and decreased ox-LDL concentrations by 31.72 U/l (p = 0.015)., Conclusion: At 5-weeks, the consumption of 150 mg/day of OP improve lipid cardiovascular profile and represents one of the scarce ways to increase HDL-c in stage-1-hypertensive subjects., Trial Registration: ClinicalTrials.gov: NCT02063477., (Copyright © 2016. Published by Elsevier GmbH.)

Unlabelled: Hepatitis B virus (HBV) is a major human pathogen, and about one third of the global population will be exposed to the virus in their lifetime. HBV infects hepatocytes, where it replicates its DNA and infection can lead to acute and chronic hepatitis with a high risk of liver cirrhosis and hepatocellular carcinoma. Despite this, there is limited understanding of how HBV establishes chronic infections. In recent years it has emerged that foreign DNA potently stimulates the innate immune response, particularly type 1 interferon (IFN) production; and this occurs through a pathway dependent on the DNA sensor cyclic guanosine monophosphate-adenosine monophosphate synthase and the downstream adaptor protein stimulator of IFN genes (STING). In this work we describe that human and murine hepatocytes do not express STING. Consequently, hepatocytes do not produce type 1 IFN in response to foreign DNA or HBV infection and mice lacking STING or cyclic guanosine monophosphate-adenosine monophosphate synthase exhibit unaltered ability to control infection in an adenovirus-HBV model. Stimulation of IFN production in the murine liver by administration of synthetic RNA decreases virus infection, thus demonstrating that IFN possesses anti-HBV activity in the liver. Importantly, introduction of STING expression specifically in hepatocytes reconstitutes the DNA sensing pathway, which leads to improved control of HBV in vivo., Conclusion: The lack of a functional innate DNA-sensing pathway in hepatocytes hampers efficient innate control of HBV infection; this may explain why HBV has adapted to specifically replicate in hepatocytes and could contribute to the weak capacity of this cell type to clear HBV infection. (Hepatology 2016;64:746-759)., (© 2016 by the American Association for the Study of Liver Diseases.)

Scope: Lipoprotein particle measures performed by nuclear magnetic resonance (NMR), and associated ratios, may be better markers for atherosclerosis risk than conventional lipid measures. The effect of two functional olive oils, one enriched with its polyphenols (FVOO, 500 ppm), and the other (FVOOT) with them (250 ppm) and those of thyme (250 ppm), versus a standard virgin olive oil (VOO), on lipoprotein particle atherogenic ratios and subclasses profiles was assessed., Methods and Results: In a randomized, double-blind, crossover, controlled trial, 33 hypercholesterolemic individuals received 25 mL/day of VOO, FVOO, and FVOOT. Intervention periods were of 3 weeks separated by 2-week washout periods. Lipoprotein particle counts and subclasses were measured by NMR. Polyphenols from olive oil and thyme modified the lipoprotein subclasses profile and decreased the total LDL particle/total HDL particle (HDL-P), small HDL/large HDL, and HDL-cholesterol/HDL-P ratios, and decreased the lipoprotein insulin resistance index (LP-IR) (p < 0.05)., Conclusion: Olive oil polyphenols, and those from thyme provided benefits on lipoprotein particle atherogenic ratios and subclasses profile distribution. Polyphenol-enriched olive oil is a way of increasing the olive oil healthy properties while consuming the same amount of fat, as well as a useful and complementary tool for the management of cardiovascular risk individuals., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Armolipid Plus (AP) is a nutraceutical that contains policosanol, fermented rice with red yeast, berberine, coenzyme Q10, folic acid, and astaxanthin. It has been shown to be effective in reducing plasma LDL cholesterol (LDLc) levels. In the multicenter randomized trial NCT01562080, there was large interindividual variability in the plasma LDLc response to AP supplementation. We hypothesized that the variability in LDLc response to AP supplementation may be linked to LDLR and PCSK9 polymorphisms., Material and Methods: We sequenced the LDLR 3' and 5' untranslated regions (UTR) and the PCSK9 5' UTR of 102 participants with moderate hypercholesterolemia in trial NCT01562080. In this trial, 50 individuals were treated with AP supplementation and the rest with placebo., Results: Multiple linear regression analysis, using the response of LDLc levels to AP as the dependent variable, revealed that polymorphisms rs2149041 (c.-3383C>G) in the PCSK9 5' UTR and rs14158 (c.*52G>A) in the LDLR 3' UTR explained 14.1% and 6.4%, respectively, of the variability after adjusting for gender, age, and BMI of individuals. Combining polymorphisms rs2149041 and rs14158 explained 20.5% of this variability (p < 0.004)., Conclusions: Three polymorphisms in the 3' UTR region of LDLR, c.*52G>A, c.*504G>A, and c.*773A>G, and two at the 5' UTR region of PCSK9, c.-3383C>G and c.-2063A>G, were associated with response to AP. These results could explain the variability observed in the response to berberine among people with moderate hypercholesterolemia, and they may be useful in identifying patients who could potentially benefit from supplementation with AP.