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.

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).

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.

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.