Emerging evidence indicates that omega-3 fatty acids from fish oil may serve as beneficial dietary supplements for psoriasis management. Clinical observations demonstrate a significant association between psoriasis improvement and increased docosahexaenoic acid (DHA) levels. However, the causal relationship between fatty acids and psoriasis risk requires further investigation. Using summary-level genome-wide association study (GWAS) data, we applied univariable (UVMR), reverse, and multivariable (MVMR) Mendelian randomization analyses to assess causal effects of multiple fatty acids-including polyunsaturated (PUFA), saturated (SFA), monounsaturated (MUFA), omega-3/6 fatty acids, DHA, eicosapentaenoate (EPA) and docosapentaenoate (DPA)-on psoriasis risk. The analysis revealed that higher circulating levels of omega-3 fatty acids were significantly associated with a reduced risk of psoriasis development (UVMR: OR = 0.900, p = 0.022; MVMR: OR = 0.862, p = 0.007). Sensitivity analyses supported the robustness of this causal relationship, with consistent effects across multiple MR methods. Notably, DHA (UVMR: OR = 0.788, p = 0.006; MVMR: OR = 0.856, p = 0.021) drove this inverse association, while EPA and DPA showed marginal contributions. This study provides valuable insights for targeted nutritional strategies to prevent and manage psoriasis, but further validation is needed.
