Associations Between Dietary Intakes of Omega-3 Fatty Acids, Blood Levels, and Pain Interference in People with Migraine: A Path Analysis of Randomized Trial Data

<b>Background/Objectives:</b> Increasing evidence supports the hypothesis that dietary intervention can improve pain among individuals with headaches, including migraine, a highly prevalent condition that can be disabling. Non-pharmacologic treatments for migraine are particularly attractive. In this secondary analysis of 182 participants enrolled in a randomized controlled trial of a dietary intervention designed to increase omega-3 (<i>n</i>-3) compared with a control diet, we examined the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), both thought to decrease inflammatory processes. <b>Methods:</b> Path models with two time points (baseline and 16 weeks after randomization), were used to test the relationships between exposures of <i>n</i>-3 blood levels and self-reported dietary intake on outcomes of pain interference using the PROMIS pain interference scale and the Headache Impact Test (HIT-6). Model building was based on our published conceptual model. <b>Results:</b> Good fit was demonstrated for both models (EPA model: CFI = 0.984, RMSEA = 0.039, and SRMR = 0.045; DHA model: CFI = 0.981, RMSEA = 0.040, and SRMR = 0.040). Both EPA and DHA in the blood at 16 weeks were associated with lower levels of pain interference, but the effect for EPA was stronger (B = -0.56, <i>p</i> < 0.001 for EPA, and B = -0.43, <i>p</i> = 0.057 for DHA). <b>Conclusions:</b> Our findings are consistent with an indirect pathway linking diet to pain interference through blood levels of EPA and DHA in migraine.