Targeting epigenetic checkpoints in autoimmune diseases: Nutritional and lifestyle interventions

Abstract

Autoimmune diseases are complex disorders arising from interactions among genetic susceptibility, epigenetic regulation, and environmental exposures. Accumulating evidence indicates that DNA methylation, histone modifications, and non-coding RNAs (ncRNAs) may mediate some of the effects of environmental factors on immune function and inflammatory responses. This narrative review examines how nutritional and lifestyle-related factors may influence epigenetic pathways relevant to autoimmune diseases. Evidence from in vitro studies, preclinical models, observational research, and emerging clinical investigations is synthesized, with particular emphasis on methyl-donor nutrients, selected bioactive compounds such as curcumin, vitamin D, physical activity, sleep and circadian regulation, and chronic psychological stress. Current findings suggest that these factors may modulate immune-related epigenetic processes; however, their clinical relevance remains constrained by differences in bioavailability, tissue specificity, individual biological variability, study design, and long-term adherence. Further longitudinal and intervention studies are therefore required to establish causality and clinical effectiveness. Overall, integrating nutritional and lifestyle factors with epigenetic and clinical profiling may support the future development of personalized adjunctive strategies for autoimmune disease management.