Considering the potential impact of alcohol consumption on depression-related metabolites (45), we performed a two-step Mendelian randomization study, incorporating inflammation levels [including IL-6 (24) and CRP (25)], diet-related metabolites (28) (such as vitamin A, mannitol, and hippuric acid), acid sphingomyelinase (16), body mass index (26), and BFP (27) as mediating factors. This evidence concerns the gene CRP and major depressive disorder.