Study finds high intake of ultra-processed foods tied to reduced DNA methylation. Researchers have found that women who consume more ultra-processed foods exhibit widespread differences in DNA methylation, suggesting early biological changes that may explain how diet leaves a molecular imprint on health. Brief Report: High Consumption of Ultra-Processed Foods Is Associated with Genome-Wide DNA Methylation Differences in Women: A Pilot Study (https://www.mdpi.com/2072-6643/17/21/3465) . Image Credit: Rimma Bondarenko / Shutterstock. In a recent Brief Report in the journal Nutrients (https://www.mdpi.com/2072-6643/17/21/3465), researchers explored how consuming ultra-processed foods (UPFs) affects epigenetic regulation, specifically in peripheral blood leukocytes of women, through a process called deoxyribonucleic acid (DNA) methylation. They found that women who consumed more UPFs showed 80 differentially methylated regions (DMRs) at nominal p<0.05 (uncorrected for multiple testing) compared with those who consumed less. In most cases, DNA methylation activity was reduced (hypomethylated). Since this process is crucial to many biological functions, these exploratory results suggest a potential epigenetic link between UPF intake and health outcomes, though causality cannot be inferred. What Defines Ultra-Processed Foods According to the NOVA system, UPFs include ready-made meals, packaged snacks, and soft drinks. These foods are highly processed and contain preservatives, flavorings, colorings, and additives. They are designed to be convenient, tasty, and have a long shelf life. Growing Global Consumption and Associated Health Risks The global rise in UPF consumption parallels increases in obesity and chronic diseases, with UPFs now contributing up to half of total calorie intake in high-income countries. They are often energy-dense, low in essential nutrients, and contain high levels of unhealthy fats, sugar, and salt. Beyond their poor nutritional profile, UPFs may also harm health through non-nutritional factors such as altered food structure, contaminants, and additives. High consumption has been linked to mental health and cardiovascular conditions, weight gain, metabolic disorders, and even accelerated biological aging. Epigenetic Mechanisms Linking Diet and Disease The biological mechanisms behind these associations are not fully understood. One promising explanation is epigenetic modification, specifically DNA methylation, which can influence how genes are expressed in response to environmental factors, such as diet. Study Design and Participant Selection Researchers conducted a cross-sectional exploratory pilot study that included 30 women between 20 and 40 years old, with a body mass index (BMI) between 18.5 and 39.9 kg/m², recruited from a previous project. Participants were excluded if they had conditions or behaviors affecting metabolism, such as over-exercising, amenorrhea, infectious diseases, cancer, breastfeeding, or medication use that could affect weight or eating behavior, as well as eating disorders, chronic illness, pregnancy, smoking, or drug dependence. The study received ethical approval, and all participants provided written consent. Dietary Assessment and Classification of UPFs Dietary intake was assessed using three-day food records (two weekdays and one weekend day). Foods were categorized according to the NOVA classification, and the proportion of total energy from UPFs was calculated. Habitual intake was estimated using the Multiple Source Method (MSM) to reduce day-to-day variation. Participants were divided into tertiles based on UPF consumption, and those in the lowest and highest tertiles were included in the epigenetic analysis. Anthropometric measurements, body composition, and biochemical markers were also recorded. DNA Methylation Analysis and Statistical Evaluation DNA was extracted from participants’ peripheral blood leukocytes. Genome-wide DNA methylation profiling was conducted using next-generation sequencing (NGS) after DNA enrichment and bisulfite conversion. Data were processed with bioinformatics tools, and differentially methylated regions were identified. Statistical tests (t-test or Mann–Whitney U) were used to compare variables between groups, and correlations among methylated regions were evaluated using Pearson’s test. Regions showing more than fourfold methylation differences were highlighted for visualization through heatmaps. Key Findings and Biological Implications Participants were grouped according to their intake of UPFs. The low-UPF group consumed an average of 14% of total energy from UPFs, while the high-UPF group consumed 45%. Of 20 DNA samples analyzed, five were excluded due to poor sequencing quality, leaving 15 valid samples (7 low-UPF and eight high-UPF participants). The women had a median age of 31 years and an average BMI of 24.7 kg/m², with no significant differences in body composition or anthropometric measurements between the two groups. Biochemical tests showed unexpectedly higher total, low-density lipoprotein (LDL), and non-high-density lipoprotein (HDL) cholesterol levels in the low-UPF group. This finding aligns with previous research, including that of Dicken et al. (2025), which suggests that short-term UPF intake may not always elevate blood lipids, underscoring the complexity of UPF-lipid relationships. Diet comparisons revealed that the low-UPF group consumed more unprocessed foods, protein, and polyunsaturated fats. Genome-wide DNA methylation analysis identified 80 differentially methylated regions (DMRs), primarily located in gene promoter areas. After filtering for regions with greater than fourfold differences, seven regions, RNA5S7, RNA5S9, RNA5S13, LINC00396, FOXP1-AS1, LOC124902961, and REPIN1-AS1, showed the largest methylation differences. These regions were emphasized for visualization rather than being considered the only statistically significant sites. Most DMRs were hypomethylated in the high-UPF group, indicating that higher UPF intake is associated with lower DNA methylation levels across multiple genomic regions. Study Conclusions and Future Research Directions This pilot study was the first to utilize NGS to assess genome-wide DNA methylation changes associated with UPF consumption. The results revealed 80 regions with differential methylation, mainly hypomethylated in women with high UPF intake. Some of the most affected genes, such as FOXP1-AS1 and REPIN1-AS1, are involved in metabolic regulation and cancer-related pathways, suggesting possible biological links between UPF intake and adverse health effects. Key strengths include the use of a high-resolution NGS approach, unbiased genome-wide analysis, and accurate dietary assessment using three-day food records. However, the small sample size limited statistical power, and the cross-sectional design prevents causal interpretation. P values were nominal, unadjusted for multiple comparisons, and reflect exploratory analysis in a small sample, increasing the possibility of false-positive results. DNA methylation patterns were assessed in blood, which may not reflect methylation in other tissues, and micronutrient data were lacking. Confounder adjustment (for factors such as BMI or age) was not possible due to the limited sample size. Despite these limitations, the study indicates that UPF consumption may influence gene regulation through epigenetic modifications, representing a hypothesis-generating step that warrants replication in larger, longitudinal cohorts. Journal reference: Rodrigues, A.E., Fernandes, A.E., Carrasco, A.G.M., Pellenz, F.M., Lopes da Rosa, P.W., da Silva Hourneaux de Moura, A.M., Galvão de Oliveira Santin, F., Cercato, C., de Melo, M.E., Mancini, M.C. (2025). Nutrients 17(21), 3465. DOI: 10.3390/nu17213465, https://www.mdpi.com/2072-6643/17/21/3465
