Mediterranean diet: definitions, health effects and metabolic pathways - evidence and future directions.

The Mediterranean diet (MedDiet) is one of the most extensively studied dietary patterns in relation to chronic disease prevention and management. MedDiet reflects a plant-forward dietary model characterized by high intake of fruits, vegetables, legumes, whole grains, nuts, and olive oil, moderate consumption of fish and dairy, low intake of red and processed meats, and optional moderate wine intake with meals. This review summarizes current evidence linking adherence to the MedDiet with major health outcomes, including cardiovascular disease, type 2 diabetes mellitus, metabolic dysfunction-associated steatotic liver disease, chronic kidney disease, neurodegenerative disorders, and cancer. Evidence from prospective cohort studies, randomized controlled trials, and meta-analyses consistently supports protective associations, particularly for cardiovascular and metabolic endpoints. Biological pathways underlying these effects include modulation of inflammation, oxidative stress, endothelial function, thrombosis, gut microbiome composition and/or function, and metabolomic profiles. Advances in metabolomics and microbiome research provide emerging insight into potential intermediary mechanisms linking dietary exposure to disease risk. Methodological challenges in assessing adherence and heterogeneity in scoring systems are also discussed as well as future research priorities.