Nutritional Epigenetics of Vitamin Intake (A, B1, B2, B3, B6, B12, and E): Associations with Genome-Wide DNA Methylation

Background/Objectives: DNA methylation is a key epigenetic mechanism involved in gene regulation and chromatin stability and may be influenced by nutritional exposures. However, population-level evidence regarding associations between dietary vitamin intake and genome-wide DNA methylation remains limited. Methods: We investigated associations between dietary intake of vitamins A, B1, B2, B3, B6, B12, and E and blood DNA methylation in 2030 participants from the Southern Community Cohort Study (SCCS). Dietary intake was assessed using a validated Food Frequency Questionnaire, and genome-wide DNA methylation was profiled using the Illumina Infinium MethylationEPIC v2.0 BeadChip. Epigenome-wide association analyses were conducted using robust linear regression models adjusted for demographic, lifestyle, and estimated cellular composition variables. Results: We identified 34 CpG sites associated with dietary intake of vitamins B1, B2, B3, B6, and E, at a false discovery rate-adjusted p-value (FDR_p) threshold of <0.1. The strongest association was observed between vitamin B6 intake and cg19831775 (Beta = −0.111, FDR_p = 0.015). No statistically significant associations were identified for vitamins A and B12. Most observed effects were modest, and associations were locus-specific rather than global. Race- and sex-stratified analyses demonstrated generally consistent directions of association, although statistical significance was attenuated in subgroup analyses. Conclusions: These findings provide suggestive evidence that dietary intake of vitamins B1, B2, B3, B6 and E may be associated with subtle variation in DNA methylation at specific genomic loci.