Purpose To assess the effect of the intake of a single dose of high-polyphenols cocoa on gene expression in peripheral mononuclear cells (PBMCs), and analyze conjugated (−)-epicatechin metabolites in plasma, which may be related with an antioxidant response in healthy human. Methods A randomized, controlled, double-blind, cross-over, clinical trial in healthy young adults who consumed a single dose of high-polyphenols cocoa powder and maltodextrins as control, with a one-week washout period. Analysis of circulating metabolites, plasma antioxidant capacity and gene expression changes in PBMCs were performed under fasting conditions and 2-h after treatment using microarray in a subsample. Pathway analysis was conducted using Ingenuity Pathway Analysis (IPA). Results Twenty healthy participants (9 F) were included in the study. A significant increase in circulating (−)-epicatechin metabolites was found after cocoa intake in all participants without related changes in antioxidant capacity of plasma. The metabolites profile slightly varied across subjects. Treatments triggered different transcriptional changes in PBMC. A group of 98 genes showed changes in expression after cocoa treatment, while only 18 were modified by control. Differentially expressed genes included inflammatory cytokines and other molecules involved in redox balance. Gene and network analysis after cocoa intake converged in functions annotated as decreased production of reactive oxygen species (p = 9.58E−04), decreased leukocyte activation (p = 4E−03) and calcium mobilization (p = 2.51E–05). Conclusions No association was found between conjugated metabolites in plasma and antioxidant capacity. Changes in PBMCs gene expression suggest anti-inflammatory effects.

Polyunsaturated fatty acids (PUFA) contained in fish oil (FO) are ligands for peroxisome proliferator-activated receptors (PPAR) that may induce changes in cardiometabolic markers. Variation in PPAR genes may influence the beneficial responses linked to FO supplementation in young adults. The study aimed to analyze the effect of FO supplementation on glucose metabolism, circulating lipids and inflammation according to PPARα L162V and PPARγ2 P12A genotypes in young Mexican adults. 191 young, non-smoking subjects between 18 and 40 years were included in a one-arm study. Participants were supplemented with 2.7 g/day of EPA+DHA, during six weeks. Dietary analysis, body composition measurements and indicators for glucose metabolism, circulating lipids, and markers for inflammation were analyzed before and after intervention. An overall decrease in triglycerides (TG) and an increase in HS-ω3 index were observed in all subjects [-4.1 mg/dL, (SD:±51.7), P=.02 and 2.6%, (SD:±1.2), P<.001 respectively]. Mean fasting insulin and glycated hemoglobin (HbA1c%) were significantly decreased in all subjects [-0.547mlU/L, (SD:±10.29), P=.034 and-0.07%, (SD:±0.3), P<.001 respectively], whereas there was no change in body composition, fasting glucose, adiponectin and inflammatory markers. Subjects carrying the minor alleles of PPARα L162V and PPARγ2 P12A had higher responses in reduction of TG and fasting insulin respectively. Interestingly, doses below 2.7 g/day (1.8 g/day) were sufficient to induce a significant reduction in fasting insulin and HbA1c% from baseline (P=.019 and P<.001). The observed responses in triglycerides and fasting insulin in the Mexican population give further evidence of the importance of FO supplementation in young people as an early step towards the prevention of cardiometabolic disease.

Background: While the bioavailability of cocoa polyphenols, particularly of the monomer (-)-epicatechin, has been investigated after a single-dose intake, the effect of sustained cocoa consumption on the metabolic profile of the structurally related (-)-epicatechin metabolites (SREMs) has not been investigated. Methods: A randomized, controlled crossover clinical trial in healthy young adults (18–40 year) was conducted to evaluate SREMs after consumption of a single-dose and after daily consumption of 1.3 g of polyphenol-rich cocoa powder for 28 days. The circulating SREMs were measured by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Results: Twenty subjects (eleven males and nine females) were enrolled. The SREMs concentrations increased to 1741 ± 337 nM after a single-dose and to 1445 ± 270 nM after sustained supplementation. Sulfate conjugates showed higher levels in females (p < 0.05). The epicatechin-3′-glucuronide (E3′G) and epicatechin-3′-sulfate (E3′S) were the most abundant metabolites in all subjects. A high intra-individual correlation (r = 0.72, p < 0.001) between SREMs concentrations after single-dose and sustained supplementation was observed. The antioxidant capacity of plasma did not change in response to the intervention and was not correlated with any of the SREMs. Conclusion: The individual SREMs profile and concentrations after a 28-day supplementation are comparable to those after a single dose.