The Short-term Effect Of Cocoa Product Consumption On Lipid Profile: A Meta-analysis Of Randomized Controlled Trials

Background:The effect of cocoa products on lipid changes is still controversial. Objectives:We aimed to identify and quantify the effect of cocoa on total cholesterol (TC), low density lipoprotein cholesterol (LDL) and high density lipoprotein cholesterol (HDL).Design:A comprehensive literature search was conducted for relevant trials of cocoa on lipid profile. Weighted mean differences were calculated for net changes in lipid concentrations by using fixed-effect or random-effect models. Previously defined subgroup analyses were performed to identify the source of heterogeneity.Results:Eight trials (215 participants) were included and evaluated. Because there was only one relatively longer term study, we focused on the short-term data to evaluate the effects of cocoa on plasma lipid. Cocoa consumption significantly reduced LDL by 5.87 mg/dL (95%CI:-11.13,-0.61; P<0.05) and marginally decreased TC by 5.82 mg/dL (95%CI:-12.39,0.76; P=0.08). However, no significant change was seen in LDL in the high-quality studies (3 studies included,-4.98 mg/dL,95%CI:-13.18,3.21,P=0.23). Subgroup analyses suggested that the cholesterol-lowering effect only was identified in those with low dose of cocoa consumption and with cardiovascular disease risks. No evidence was found in supporting a dose-effect relationship, of any effect in healthy subjects, or of any change in HDL.Conclusion:Short-term cocoa consumption significantly reduced blood cholesterol, but the effects were dependent on the dose of cocoa consumption and the healthy status of participants. No dose response and no effect were found in healthy participants. Future high quality studies are needed to determine the efficiency of moderate cocoa on lipid profile in long-term intervention and in subjects with other cardiometabolic risk factors. Objective:Regulatory T (Treg) cells play a protective role in experimental atherosclerosis. However, the role of Treg in the development of human coronary artery disease (CAD) is still inconsistent. Demethylation in the DNA that encodes transcription factor forkhead box P3 (FOXP3) is a prerequisite for the stable maintenance of suppressive properties in Tregs, which is also identified as the most specific marker for human Tregs. We aim to evaluate Treg levels in CAD patients by a novel method based on Treg-specific DNA demethylation within FOXP3 gene and testify DNA methylation modification of FOXP3 in the development of atherosclerosis.Methods and Results:We included acute ST-elevation myocardial infarction (STEMI) patients, non-ST-elevation acute coronary syndromes (NSTACS) patients, and control subjects with normal coronary artery on angiography (NCA) in our study. Peripheral blood mononuclear cells were collected to determine Treg levels by both flow cytometry and PCR based DNA methylation analysis. We found that Treg levels, quantified by the demethylation rate of Treg-specific demethylated region in FOXP3 gene, but not by flow cytometry, were univocally decreased in NSTACS and in STEMI patients (NCA 4.22%±1.92%; NSTACS 3.29%±1.45%; AMI 2.86%±1.26%). This decline was inversely related to the severity of CAD (?=-0.308,p<0.05). After adjustment for traditional risk factors, the association remained (/?=-0.336, P<0.05). Furthermore, we detected the expression of DNA methyltransferases in CD4+CD25+Tregs sorted from included subjects. A significant increase of DNA methyltransferase 3b was observed in CAD patients compared with normal controls. Treatment of CD4+CD25+Tregs with ox-LDL induced a 41%increase in the methylation of FOXP3, accompanied with a more than 3-fold reduction of FOXP3 mRNA expression and increases in the expressions of DNA methyltransferase 3a and 3b. Moreover, the effect of ox-LDL on Tregs can be reversed by methyltransferase inhibitor (-)-epigallocatechin-3-gallate.Conclusion:Our data demonstrate that Treg cells are decreased in CAD patients and its reduction are associated with the severity of atherosclerosis. Ox-LDL decreases the expression of FOXP3 by DNA methylation. Thus, we confirm the important role of Treg cells in human CAD and suggest potential epigenetic regulation in the progression of atherosclerosis.