A 16-month follow-up after a youth-led social marketing intervention to encourage healthy lifestyles in children (aged 9 at baseline and 11 at follow-up) from disadvantaged neighbourhoods: the European Youth Tackling Obesity-Kids project.

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.

Effects of enriched seafood sticks (heat-inactivated B. animalis subsp. lactis CECT 8145, inulin, omega-3) on cardiometabolic risk factors and gut microbiota in abdominally obese subjects: randomized controlled trial.

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: (1010 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).

Fermented dairy foods rich in probiotics and cardiometabolic risk factors: a narrative review from prospective cohort studies.

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.

Effects of hesperidin in orange juice on blood and pulse pressures in mildly hypertensive individuals: a randomized controlled trial (Citrus study).

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.

Effects of daily consumption of the probiotic Bifidobacterium animalis subsp. lactis CECT 8145 on anthropometric adiposity biomarkers in abdominally obese subjects: a randomized controlled trial.

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 1010 colony forming unit (CFU) of Ba8145, 1010 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.

Nontargeted metabolite profiling discriminates diet-specific biomarkers for consumption of whole grains, fatty fish, and bilberries in a randomized controlled trial.

BACKGROUND: Nontargeted metabolite profiling allows for concomitant examination of a wide range of metabolite species, elucidating the metabolic alterations caused by dietary interventions. OBJECTIVE: The aim of the current study was to investigate the effects of dietary modifications on the basis of increasing consumption of whole grains, fatty fish, and bilberries on plasma metabolite profiles to identify applicable biomarkers for dietary intake and endogenous metabolism. METHODS: Metabolite profiling analysis was performed on fasting plasma samples collected in a 12-wk parallel-group intervention with 106 participants with features of metabolic syndrome who were randomly assigned to 3 dietary interventions: 1) whole-grain products, fatty fish, and bilberries [healthy diet (HD)]; 2) a whole-grain-enriched diet with the same grain products as in the HD intervention but with no change in fish or berry consumption; and 3) refined-wheat breads and restrictions on fish and berries (control diet). In addition, correlation analyses were conducted with the food intake data to define the food items correlating with the biomarker candidates. RESULTS: Nontargeted metabolite profiling showed marked differences in fasting plasma after the intervention diets compared with the control diet. In both intervention groups, a significant increase was observed in 2 signals identified as glucuronidated alk(en)-ylresorcinols [corrected P value (Pcorr) < 0.05], which correlated strongly with the intake of whole-grain products (r = 0.63, P < 0.001). In addition, the HD intervention increased the signals for furan fatty acids [3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF)], hippuric acid, and various lipid species incorporating polyunsaturated fatty acids (Pcorr < 0.05). In particular, plasma CMPF correlated strongly with the intake of fish (r = 0.47, P < 0.001) but not with intakes of any other foods. CONCLUSIONS: Novel biomarkers of the intake of health-beneficial food items included in the Nordic diet were identified by the metabolite profiling of fasting plasma and confirmed by the correlation analyses with dietary records. The one with the most potential was CMPF, which was shown to be a highly specific biomarker for fatty fish intake. This trial was registered at clinicaltrials.gov as NCT00573781.

Olive oil polyphenols enhance high-density lipoprotein function in humans: a randomized controlled trial.

OBJECTIVE: Olive oil polyphenols have shown beneficial properties against cardiovascular risk factors. Their consumption has been associated with higher cholesterol content in high-density lipoproteins (HDL). However, data on polyphenol effects on HDL quality are scarce. We, therefore, assessed whether polyphenol-rich olive oil consumption could enhance the HDL main function, its cholesterol efflux capacity, and some of its quality-related properties, such HDL polyphenol content, size, and composition. APPROACH AND RESULTS: A randomized, crossover, controlled trial with 47 healthy European male volunteers was performed. Participants ingested 25 mL/d of polyphenol-poor (2.7 mg/kg) or polyphenol-rich (366 mg/kg) raw olive oil in 3-week intervention periods, preceded by 2-week washout periods. HDL cholesterol efflux capacity significantly improved after polyphenol-rich intervention versus the polyphenol-poor one (+3.05% and -2.34%, respectively; P=0.042). Incorporation of olive oil polyphenol biological metabolites to HDL, as well as large HDL (HDL2) levels, was higher after the polyphenol-rich olive oil intervention, compared with the polyphenol-poor one. Small HDL (HDL3) levels decreased, the HDL core became triglyceride-poor, and HDL fluidity increased after the polyphenol-rich intervention. CONCLUSIONS: Olive oil polyphenols promote the main HDL antiatherogenic function, its cholesterol efflux capacity. These polyphenols increased HDL size, promoted a greater HDL stability reflected as a triglyceride-poor core, and enhanced the HDL oxidative status, through an increase in the olive oil polyphenol metabolites content in the lipoprotein. Our results provide for the first time a first-level evidence of an enhancement in HDL function by polyphenol-rich olive oil.

New Perspectives for Low Muscle Mass Quantity/Quality Assessment in Probable Sarcopenic Older Adults: An Exploratory Analysis Study.

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.

A red-fleshed apple rich in anthocyanins improves endothelial function, reduces inflammation, and modulates the immune system in hypercholesterolemic subjects: the AppleCOR study.

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.

A single-blinded, randomized, parallel intervention to evaluate genetics and omics-based personalized nutrition in general population via an e-commerce tool: The PREVENTOMICS e-commerce study.

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 (ß: -0.37; 95% CI: -0.56, -0.18), oxidative stress (ß: -0.37; 95% CI: -0.60, -0.15), microbiota (ß: -0.38; 95% CI: -0.63, -0.15), and inflammation (ß: -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).

The effects of fatty acid-based dietary interventions on circulating bioactive lipid levels as intermediate biomarkers of health, cardiovascular disease, and cardiovascular disease risk factors: a systematic review and meta-analysis of randomized clinical trials.

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.

Assessment of human inter-individual variability of phloretin metabolites in urine after apple consumption. AppleCOR study.

Purpose: This study aimed to assess the inter-individual variation in phloretin absorption and metabolism and to seek possible phloretin metabotypes following apple snack consumption. Methods: The excreted phloretin metabolites in 24 h urine samples were determined by UPLC-MS/MS in 62 volunteers after acute and sustained (6 weeks) interventions in a randomized and parallel study with a daily supplementation of 80 g of a low-phloretin (39.5 µmol) or a high-phloretin (103 µmol) freeze-dried apple snacks. Results: absorption estimated as phloridzin equivalents for 62 volunteers varied almost 70-fold ranging from 0.1% to 6.94% of phloretin glycoside intake. Volunteers were stratified into low, medium and high producers and by the balance between glucuronidation and sulphation. For 74% of the volunteers phloretin-O-glucuronide was the dominant urinary metabolite, especially at the higher phloretin glycoside intake and for higher producers. Sulphate conjugation assumed greater significance for the remaining volunteers especially for low producers. Females dominated glucuronide profile (64.1%) and males dominated the low excretion group. Analysis of plasma glucose and insulin at the start and end of the sustained study showed a trend towards modest reductions for high producers. Furthermore, plausible factors contributing to the inter-individual variation in phloretin uptake are discussed. Conclusions: extensive inter-individual variability exists in the excretion of phloretin phase-II conjugates following consumption of apple snacks, which could be related to oral microbiota phloridzin-hydrolysing activity, lactase non-persistence trait or the metabotype to which the subject belongs. There were inconsistent effects on post-prandial serum glucose concentrations but there was a tendency for decreases to be associated with higher excretion of phloretin phase-II conjugates. Trial registration: The acute and sustained studies were registered at ClinicalTrials.gov Identifier: NCT03795324.

Impact of an Intervention on Healthy Offerings and Allergenic Food Management in Restaurants: A Parallel Randomized Controlled Study.

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.

Mediterranean Diet and Lung Function in Adults Current Smokers: A Cross-Sectional Analysis in the MEDISTAR Project.

BACKGROUND: Previous studies have shown that adherence to the Mediterranean Diet (MeDi) has a positive impact on lung function in subjects with lung disease. In subjects free of respiratory diseases, but at risk, this association is not yet well established. METHODS: Based on the reference data from the MEDISTAR clinical trial (Mediterranean Diet and Smoking in Tarragona and Reus; ISRCTN 03.362.372), an observational study was conducted with 403 middle-aged smokers without lung disease, treated at 20 centres of primary care in Tarragona (Catalonia, Spain). The degree of MeDi adherence was evaluated according to a 14-item questionnaire, and adherence was defined in three groups (low, medium, and high). Lung function were assessed by forced spirometry. Logistic regression and linear regression models were used to analyse the association between adherence to the MeDi and the presence of ventilatory defects. RESULTS: Globally, the pulmonary alteration prevalence (impaired FEV1 and/or FVC) was 28.8%, although it was lower in participants with medium and high adherence to the MeDi, compared to those with a low score (24.2% and 27.4% vs. 38.5%, p = 0.004). Logistic regression models showed a significant and independent association between medium and high adherence to the MeDi and the presence of altered lung patterns (OR 0.467 [95%CI 0.266, 0.820] and 0.552 [95%CI 0.313, 0.973], respectively). CONCLUSIONS: MeDi adherence is inversely associated with the risk impaired lung function. These results indicate that healthy diet behaviours can be modifiable risk factors to protect lung function and reinforce the possibility of a nutritional intervention to increase adherence to MeDi, in addition to promoting smoking cessation.

Developing a model to predict the early risk of hypertriglyceridemia based on inhibiting lipoprotein lipase (LPL): a translational study.

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.

A Fluorescence-Based In Vitro Method to Assess Cholesterol Efflux.

Cholesterol efflux (ChE) capacity is associated with the incidence of cardiovascular events and has been proposed as an emerging cardiovascular risk factor. ChE has been traditionally assessed by in vitro radioactive methods but these are not appropriate when assessing a large number of samples. Therefore, alternative, reproducible nonradioactive methods have been developed. This chapter describes a robust nonradioactive method using a fluorescent tracer to assess ChE in vitro.The measurement of ChE in vitro requires three main components: a cholesterol-loaded donor cell, a cholesterol tracer, and a cholesterol acceptor. This method involves labeling of murine macrophage J774A.1 cells using the fluorescent sterol dipyrromethene boron difluoride (BODIPY)-cholesterol. The cholesterol acceptors from humans or animals include lipid-free apolipoprotein (ApoA)-1, high-density lipoprotein (HDL), HDL2 and HDL3 subfractions, serum, plasma or ApoB-depleted serum or plasma. While lipid-free ApoA-1 mediates ChE via only ATP-binding cassette (ABC)A1 transporter, the remaining acceptors mediate ChE via ABCA1 , ABCG1 and scavenger receptor class B type 1 (SRB1) transporters. The reproducibility of this BODIPY-ChE assay is excellent as the intra-assay coefficients of variation (CVs) were <10% (30 replicates on the same day) and the interassay CVs were <14% (10 experiments performed on different days, with 3 replicates each). The fluorescent method therefore represents a reproducible, safe and useful tool to evaluate ChE as an emerging cardiovascular risk factor.

Antioxidant-rich foods, antioxidant supplements, and sarcopenia in old-young adults ≥55 years old: A systematic review and meta-analysis of observational studies and randomized controlled trials.

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).

Phenol metabolic fingerprint and selection of intake biomarkers after acute and sustained consumption of red-fleshed apple versus common apple in humans. The AppleCOR study.

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.

Red-Fleshed Apples Rich in Anthocyanins and White-Fleshed Apples Modulate the Aorta and Heart Proteome in Hypercholesterolaemic Rats: The AppleCOR Study.

The impact of a red-fleshed apple (RFA) rich in anthocyanins (ACNs), a white-fleshed apple (WFA) without ACNs, and an extract infusion from Aronia fruit (AI) equivalent in dose of cyanidin-3-O-galactoside (main ACN) as RFA was determined by the proteome profile of aorta and heart as key cardiovascular tissues. Hypercholesterolaemic Wistar rats were separated into six groups (n = 6/group; three males and three females) and the proteomic profiles were analyzed using nanoliquid chromatography coupled to mass spectrometry. No adverse events were reported and all products were well tolerated. RFA downregulated C1QB and CFP in aorta and CRP in heart. WFA downregulated C1QB and CFP in aorta and C9 and C3 in aorta and heart, among other proteins. AI downregulated PRKACA, IQGAP1, and HSP90AB1 related to cellular signaling. Thus, both apples showed an anti-inflammatory effect through the complement system, while RFA reduced CRP. Regardless of the ACN content, an apple matrix effect was observed that involved different bioactive components, and inflammatory proteins were reduced.

Serum lysophospholipidome of dietary origin as a suitable susceptibility/risk biomarker of human hypercholesterolemia: A cross-sectional study.

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.