Fátima Cardoso, Eduardo Costa-Camilo, Isabel Duarte, Graça P Carvalho, Rita G Sobral, João M G C F de Almeida, Carla Pinheiro
The Mediterranean diet (MedDiet) is widely recognized for its role in preventing chronic and age-related diseases, largely attributed to its richness in plant-based foods and bioactive compounds. To explore the underlying molecular mechanisms, two systematic literature searches were conducted using PubMed and Web of Science. The first assessed the evidence on the health effects of key MedDiet components and the second focused on plasma biomarkers of inflammation and oxidative stress. Protein-protein interaction network analysis revealed a tightly connected metabolic network integrating inflammatory mediators and metabolic regulators. Central nodes included key inflammatory markers such as interleukin-6, tumor necrosis factor and C-reactive protein (CRP), alongside proteins involved in lipid metabolism and metabolic homeostasis. Enrichment analysis highlighted pathways related to acute inflammatory response, lipid localization and storage and plasma lipoprotein particle clearance, supporting a role in regulation of immune and metabolic processes. An additional network integrating cardiovascular aging biomarkers suggested a partial separation between systemic inflammatory pathways and markers of myocardial stress and injury, with CRP emerging as a potential link between these processes. Overall, these findings indicate that the MedDiet may exert its health benefits through systems-level modulation of interconnected metabolic pathways, contributing to the regulation of inflammation, lipid metabolism and cardiovascular function.