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Causal Relationship of Polyunsaturated Fatty Acids With Mental Disorders: A Systematic Review and Meta-analysis

Yao Y, Yang X, Yan J, Lv H, Yue Z, Yu J, Lin X, Qian C et al.

Nutrition reviews, 2026

Abstract

Context: Mental disorders (MDs) pose a important global health challenge, with a complex pathogenesis complicating treatment development. Nutritional interventions, particularly polyunsaturated fatty acids (PUFAs), have gained attention as potential therapeutic options.

Objective: This Mendelian randomization (MR) meta-analysis aimed to evaluate the potential causal relationship between PUFAs and MDs.

Data sources: Genome-wide association study data were utilized to analyze the association between PUFAs (including omega-3, omega-3 percentage [omega-3%], omega-6, omega-6 percentage [omega-6%], and omega-6 to omega-3 ratio) and 12 major MDs.

Data extraction: Two-sample MR technology was used to assess the role of PUFAs in MDs.

Data analysis: The MR analysis revealed that genetically predicted omega-3 was causally linked to MDs, such as obsessive-compulsive disorder, bipolar disorder, schizophrenia, and major depressive disorder. Omega-3% exhibited protective effects against emotional personality disorder. Conversely, omega-6 was inversely correlated with attention-deficit/hyperactivity disorder risk, while a high omega-6 to omega-3 ratio was associated with an increased risk of depression and other mood disorders.

Conclusion: High omega-3 levels and omega-3% may reduce the risk of MDs, whereas a high omega-6:omega-3 ratio may elevate the risk. These findings highlight the potential of PUFAs, particularly omega-3, in MD prevention and treatment, while underscoring the need for…

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