The mediating role of key amino acid and vitamin metabolite ratios in the effects of 5 dietary habits on psoriatic arthritis: A Mendelian randomization study.

The causal relationship between dietary habits and psoriatic arthritis (PsA) remains unclear, and the mediating role of human plasma metabolites in this relationship is unexamined. This study aims to elucidate the causal relationship between 80 dietary patterns and PsA using a 2-sample Mendelian randomization (MR) analysis. A 2-step MR approach was employed to investigate whether 1400 human plasma metabolites could serve as potential mediators between dietary habits and PsA. To ensure the reliability of the results, heterogeneity and pleiotropy tests were conducted. Our MR analysis identified 5 dietary factors exhibiting significant inverse causal associations with PsA risk (P < .05): red wine intake (odds ratio (OR) = 0.62), total alcohol intake (OR = 0.59), cheese intake (OR = 0.56), monthly alcohol drinks (OR = 0.66), and decaffeinated coffee preference (OR = 0.62). Mediation analysis revealed distinct metabolite pathways underlying these associations. Red wine intake-PsA relationship: Gamma/beta-tocopherol levels mediated 17.8% of the protective effect, followed by citrate (7.2% mediation). Cheese intake-PsA association: Arginine levels accounted for 7.4% of the effect, with phosphate-to-threonine ratio mediating an additional 7.2%. Decaffeinated coffee preference-PsA link: Three amino acid ratios demonstrated significant mediation-glutamate/alanine (12.2%), ornithine/glutamate (10.9%), and arginine/glutamate (8.9%). These results underscore the potential role of plasma metabolites as mediators in the causal relationship between these 5 dietary habits and PsA.