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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.)

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.

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.

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.)

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.)

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.)

Unlabelled: The effects of olive oil phenolic compounds (PCs) on HDL proteome, with respect to new aspects of cardioprotective properties, are still unknown. The aim of this study was to assess the impact on the HDL protein cargo of the intake of virgin olive oil (VOO) and two functional VOOs, enriched with their own PCs (FVOO) or complemented with thyme PCs (FVOOT), in hypercholesterolemic subjects. Eligible volunteers were recruited from the IMIM-Hospital del Mar Medical Research Institute (Spain) from April 2012 to September 2012. Thirty-three hypercholesterolemic participants (total cholesterol >200 mg/dL; 19 men and 14 women; aged 35 to 80 years) were randomized in the double-blind, controlled, cross-over VOHF clinical trial. The subjects received for 3 weeks 25 mL/day of: VOO, FVOO, or FVOOT. Using a quantitative proteomics approach, 127 HDL-associated proteins were identified. Among these, 15 were commonly differently expressed after the three VOO interventions compared to baseline, with specific changes observed for each intervention. The 15 common proteins were mainly involved in the following pathways: LXR/RXR activation, acute phase response, and atherosclerosis. The three VOOs were well tolerated by all participants. Consumption of VOO, or phenol-enriched VOOs, has an impact on the HDL proteome in a cardioprotective mode by up-regulating proteins related to cholesterol homeostasis, protection against oxidation and blood coagulation while down-regulating proteins implicated in acute-phase response, lipid transport, and immune response. The common observed protein expression modifications after the three VOOs indicate a major matrix effect., Trial Registration: International Standard Randomized Controlled Trials ISRCTN77500181.

Unlabelled: DNA methylation regulates gene expression and can be modified by different bioactive compounds in foods, such as polyphenols. Cocoa is a rich source of polyphenols, but its role in DNA methylation is still unknown. The objective was to assess the effect of cocoa consumption on DNA methylation and to determine whether the enzymes involved in the DNA methylation process participate in the mechanisms by which cocoa exerts these effects in humans. The global DNA methylation levels in the peripheral blood were evaluated in 214 volunteers who were pre-hypertensive, stage-1 hypertensive or hypercholesterolemic. The volunteers were divided into two groups: 110 subjects who consumed cocoa (6 g/d) for two weeks and 104 control subjects. In addition, the peripheral blood mononuclear cells (PBMCs) from six subjects were treated with a cocoa extract to analyze the mRNA levels of the DNA methyltransferases (DNMTs), methylenetetrahydrofolate reductase (MTHFR), and methionine synthase reductase (MTRR) genes. Cocoa consumption significantly reduced the DNA methylation levels (2.991±0.366 vs. 3.909±0.380, p<0.001). Additionally, we found an association between the cocoa effects on DNA methylation and three polymorphisms located in the MTHFR, MTRR, and DNMT3B genes. Furthermore, in PBMCs, the cocoa extract significantly lowered the mRNA levels of the DNMTs, MTHFR, and MTRR. Our study demonstrates for the first time that the consumption of cocoa decreases the global DNA methylation of peripheral leukocytes in humans with cardiovascular risk factors. In vitro experiments with PBMCs suggest that cocoa may exert this effect partially via the down-regulation of DNMTs, MTHFR and MTRR, which are key genes involved in this epigenetic process., Trial Registration: Clinicaltrials.govNCT00511420 and NCT00502047.