Dietary impacts on the human methylome – focus on vitamin intake in context of health and disease risk

Diet is a key modifiable component of health, and a major risk factor for chronic disease in humans. At the molecular level diet can affect DNA methylation (DNAm), an epigenetic process that is involved in gene expression regulation. Multiple studies have linked DNAm profiles to changes in diet across different layers. Specifically, intake of nutrients such as folate and vitamin B12 has been associated with changes in human DNAm patterns genome-wide, linking dietary intakes to the potential modulation of gene activity. In this review we present a focused overview of recent findings from epigenome-wide association studies (EWAS) in human cohorts linking intake of specific vitamins to changes in the human methylome. We also discuss current gaps in knowledge and propose future directions to explore how exactly different components of diet influence the regulation of human gene function. One conclusion is the relative consistency of CpG-level DNAm signal replication in prenatal and early-life folate studies. In contrast, while biologically plausible, evidence from adult nutritional epigenome-wide association studies remains more heterogeneous. Ultimately, nutrition represents a powerful tool with the potential to support health and influence long-term biological processes through gene regulation, offering promising avenues for strategies aimed at disease prevention and healthy aging.