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.

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.

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).

Hesperidin Bioavailability Is Increased by the Presence of 2S-Diastereoisomer and Micronization-A Randomized, Crossover and Double-Blind Clinical Trial.

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.

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).

The "Healthy Meals" web app for the assessment of nutritional content and food allergens in restaurant meals: Development, evaluation and validation.

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.

Effects of an Optimized Aged Garlic Extract on Cardiovascular Disease Risk Factors in Moderate Hypercholesterolemic Subjects: A Randomized, Crossover, Double-Blind, Sustainedand Controlled Study.

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.

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.

Effect of the consumption of hesperidin in orange juice on the transcriptomic profile of subjects with elevated blood pressure and stage 1 hypertension: A randomized controlled trial (CITRUS study).

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.

Metabolic Fate and Cardiometabolic Effects of Phenolic Compounds from Red-Fleshed Apple in Hypercholesterolemic Rats: A Comparative Study with Common White-Fleshed Apple. The AppleCOR Study.

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.

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.

Acute Effects of Turmeric Extracts on Knee Joint Pain: A Pilot, Randomized Controlled Trial.

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.

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.

Interplay between dietary phenolic compound intake and the human gut microbiome in hypertension: A cross-sectional study.

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.

Exploring the effects of phenolic compounds to reduce intestinal damage and improve the intestinal barrier integrity: A systematic review of in vivo animal studies.

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.

Impact of Phenol-Enriched Virgin Olive Oils on the Postprandial Levels of Circulating microRNAs Related to Cardiovascular Disease.

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.

Gut metagenomic and short chain fatty acids signature in hypertension: a cross-sectional study.

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_UCG-010, Christensenellaceae_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.

Fermented Dairy Products, Probiotic Supplementation, and Cardiometabolic Diseases: A Systematic Review and Meta-analysis.

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_record.php?ID=CRD42018091791.

Proteomic Analysis of Heart and Kidney Tissues in Healthy and Metabolic Syndrome Rats after Hesperidin Supplementation.

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.