Trial reportPloS one2013
Cocoa Consumption Alters the Global DNA Methylation of Peripheral Leukocytes in Humans with Cardiovascular Disease Risk Factors: A Randomized Controlled Trial.
Trial report in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00502047 (Multicentre, Comparative, Double-Blind, Two-Arm Parallel Clinical Trial of the Effects of Treatment With Plantago Ovata Husk on the Lipid Profile of Patients With Hypercholesterolemia), which is not on this map. Cited by 33 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Multicentre, Comparative, Double-Blind, Two-Arm Parallel Clinical Trial of the Effects of Treatment With Plantago Ovata Husk on the Lipid Profile of Patients With Hypercholesterolemia
Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Nutri-Epigenetic Effects of Phenolic Compounds from Extra Virgin Olive Oil: A Systematic Review.Advances in nutrition (Bethesda, Md.) · 2022Pooled it
- Effects of daily multivitamin-multimineral and cocoa extract supplementation on epigenetic aging clocks in the COSMOS randomized clinical trial.Nature medicine · 2026Trial
- The Trajectory of Epigenetic Chromatin Remodeling in Cardiometabolic Disease and its Therapeutic Implications.Journal of cardiovascular translational research · 2026Review
- Epigenetically Active Supplements and the Risk of Sports Injuries: Narrative Review from Molecular Mechanisms to Practical Implications.Nutrients · 2026Review
- Article
- Global DNA Methylation in Poorly Controlled Type 2 Diabetes Mellitus: Association with Redox and Inflammatory Biomarkers.International journal of molecular sciences · 2025Article
- Review
- Therapeutic Strategies for Angiogenesis Based on Endothelial Cell Epigenetics.Journal of cardiovascular translational research · 2024Review
- Review
- The impact of a polyphenol-rich supplement on epigenetic and cellular markers of immune age: a pilot clinical study.Frontiers in nutrition · 2024Article
- Immunomodulatory Role of Plants and Their Constituents on the Management of Metabolic Disorders: An Evidence-Based Review.Drug design, development and therapy · 2024Review
- Emerging epigenetic therapies of cardiac fibrosis and remodelling in heart failure: from basic mechanisms to early clinical development.Cardiovascular research · 2023Review
- Flavanol Consumption in Healthy Men Preserves Integrity of Immunological-Endothelial Barrier Cell Functions: Nutri(epi)genomic Analysis.Molecular nutrition & food research · 2022Article
- Epigenetic regulation in cardiovascular disease: mechanisms and advances in clinical trials.Signal transduction and targeted therapy · 2022Review
- Review
- Polyphenol-RichFrontiers in nutrition · 2021Article
- Insight into Polyphenol and Gut Microbiota Crosstalk: Are Their Metabolites the Key to Understand Protective Effects against Metabolic Disorders?Antioxidants (Basel, Switzerland) · 2020Review
- The Role of Dietary Phenolic Compounds in Epigenetic Modulation Involved in Inflammatory Processes.Antioxidants (Basel, Switzerland) · 2020Review
- Deciphering the Role of Polyphenols in Sports Performance: From Nutritional Genomics to the Gut Microbiota toward Phytonutritional Epigenomics.Nutrients · 2020Review
- Network Medicine: A Clinical Approach for Precision Medicine and Personalized Therapy in Coronary Heart Disease.Journal of atherosclerosis and thrombosis · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledDNA 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 registrationClinicaltrials.govNCT00511420 and NCT00502047.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.