Dietary and supplemental intake of vitamins C and E is associated with altered DNA methylation in an epigenome-wide association study meta-analysis

Abstract

Background: Dietary intake of antioxidants such as vitamins C and E protect against oxidative stress, and may also be associated with altered DNA methylation patterns. Methods: We meta-analysed epigenome-wide association study (EWAS) results from 11,866 participants across eight population-based cohorts to evaluate the association between self-reported dietary and supplemental intake of vitamins C and E with DNA methylation. EWAS were adjusted for age, sex, BMI, caloric intake, blood cell type proportion, smoking status, alcohol consumption, and technical covariates. Significant results of the meta-analysis were subsequently evaluated in gene set enrichment analysis (GSEA) and expression quantitative trait methylation (eQTM) analysis. Results: In meta-analysis, methylation at 4,656 CpG sites was significantly associated with vitamin C intake at FDR ≤ 0.05. The most significant CpG sites associated with vitamin C (at FDR ≤ 0.01) were enriched for pathways associated with systems development and cell signalling in GSEA, and were associated with downstream expression of genes enriched in the immune response in eQTM analysis. Furthermore, methylation at 160 CpG sites was significantly associated with vitamin E intake at FDR ≤ 0.05, but GSEA and eQTM analysis of the top most significant CpG sites associated with vitamin E did not identify significant enrichment of any biological pathways investigated. Conclusions: We identified significant associations of many CpG sites with vitamin C and E intake, and our results suggest that vitamin C intake may be associated with systems development and the immune response.

The Nutriepigenome

“…It also activates TET enzymes allowing the conversion of 5-methylcytosine to 5-hydroximethylcytosine. The water-soluble vitamin C synergistically works with hydrophobic vitamin E further acting as antioxidants [35]. A recent meta-analysis of genome wide methylation studies in response to vitamin C and E availability identified hundreds of genes hypomethylated in the presence of vitamin C and E. Notably, the results were consistent only after stratification of the cohort for age, sex and smoking status thereby confirming those as critical factors [36].…”

The Role of Selected Epigenetic Pathways in Cardiovascular Diseases as a Potential Therapeutic Target

“…Epigenetics involves a diverse set of reversible modifications to the genome that do not alter the deoxyribonucleic acid (DNA) sequence. Both the external environment and the internal microenvironment of cells and tissues influence epigenetic mechanisms that play a key role in the specification of cell fate and development of the organism [ 1 , 2 ]. Growing evidence suggests that epigenetic activity plays a fundamental role in the regulation of pathophysiological cellular processes [ 3 , 4 , 5 ].…”