A 12-week randomized double-blind clinical trial evaluated the effect of eicosapentaenoic acid (EPA) on episodic migraine (EM) prevention. Seventy participants with EM were randomly assigned to either an EPA group (2 g fish oil with 1.8 g EPA daily) or a placebo group (2 g soybean oil daily). The EPA group showed significant improvements in reducing monthly migraine days, decreasing headache severity, improving disability scores, and reducing anxiety and depression symptoms compared to the placebo group. Female participants particularly benefited from EPA, suggesting its potential in migraine management. The study found that high-dose EPA significantly reduced migraine frequency and severity, improved psychological symptoms, and enhanced quality of life without major adverse events, indicating its potential as a prophylactic for EM. The study highlights the role of EPA in mitigating inflammatory processes associated with migraine and suggests its use as a safe and effective alternative to conventional treatments. The findings support the use of EPA as a promising therapeutic option for migraine prevention.A 12-week randomized double-blind clinical trial evaluated the effect of eicosapentaenoic acid (EPA) on episodic migraine (EM) prevention. Seventy participants with EM were randomly assigned to either an EPA group (2 g fish oil with 1.8 g EPA daily) or a placebo group (2 g soybean oil daily). The EPA group showed significant improvements in reducing monthly migraine days, decreasing headache severity, improving disability scores, and reducing anxiety and depression symptoms compared to the placebo group. Female participants particularly benefited from EPA, suggesting its potential in migraine management. The study found that high-dose EPA significantly reduced migraine frequency and severity, improved psychological symptoms, and enhanced quality of life without major adverse events, indicating its potential as a prophylactic for EM. The study highlights the role of EPA in mitigating inflammatory processes associated with migraine and suggests its use as a safe and effective alternative to conventional treatments. The findings support the use of EPA as a promising therapeutic option for migraine prevention.