Precision nutrition for NAFLD: a mechanistic rationale for targeting the cytokine landscape

Non-alcoholic fatty liver disease (NAFLD) represents a significant global health burden with limited approved pharmacotherapies. This therapeutic gap necessitates exploration of alternative strategies targeting the underlying inflammatory drivers of disease progression. NAFLD pathogenesis is characterized by chronic dysregulation of the cytokine milieu, promoting the transition from simple steatosis to steatohepatitis and fibrosis. This review critically evaluates mechanistic evidence for specific nutraceuticals-omega-3 fatty acids (EPA/DHA), vitamins D, E, and B, and curcumin-in modulating these immunometabolic pathways. Accumulating evidence indicates that these agents suppress pro-inflammatory mediators (e.g., IL-6, IL-1β) and enhance anti-inflammatory signals (e.g., IL-10) through inhibition of central regulators such as NF-κB and the NLRP3 inflammasome. However, their efficacy is context-dependent, with DHA demonstrating relatively consistent anti-fibrotic effects in preclinical models, curcumin exhibiting formulation- and bioavailability-dependent benefits, and EPA and vitamin D showing variable responses across studies and disease stages. Collectively, these findings highlight cytokine-targeted precision nutrition as a promising strategy for NAFLD management and underscore the need for robust clinical trials to establish personalized therapeutic protocols.