title: Cocoa Consumption Alters the Global DNA Methylation of Peripheral Leukocytes in Humans with Cardiovascular Disease Risk Factors: A Randomized Controlled Trial.
abstract: 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.
  
  
  
  Clinicaltrials.govNCT00511420 and NCT00502047.
authors.affiliation: Centre Tecnològic de Nutrició i Salut (CTNS), TECNIO, Reus, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Crescenti
authors.forename: Rosa
authors.initials: R
authors.lastname: Solà
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Valls
authors.forename: Antoni
authors.initials: A
authors.lastname: Caimari
authors.forename: Josep M
authors.initials: JM
authors.lastname: Del Bas
authors.forename: Anna
authors.initials: A
authors.lastname: Anguera
authors.forename: Neus
authors.initials: N
authors.lastname: Anglés
authors.forename: Lluís
authors.initials: L
authors.lastname: Arola
mesh_terms: D000328:Adult; D002099:Cacao / Q000737:chemistry*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000235:genetics*; D002470:Cell Survival / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology*; D012307:Risk Factors; D059467:Transcriptome / Q000187:drug effects
chemical_list: D010936:Plant Extracts