Omega-3 Supplementation Modulates Whole-Blood EPA and DHA Without Improving Patient-Reported Outcomes in Youth with Migraine: A Quasi-Randomized Pilot Trial.

BACKGROUND/

OBJECTIVES

Omega-3 polyunsaturated fatty acids (PUFAs) influence lipid-mediated inflammatory pathways implicated in migraine, yet randomized trial data evaluating biologic effects of omega-3 supplementation in youth with migraine remain limited. This pilot quasi-randomized clinical trial aimed to determine whether 12 weeks of omega-3 PUFA supplementation produces measurable changes in whole-blood EPA and DHA levels in children and adolescents with migraine, and to characterize changes in patient-reported measures of pain, migraine-related disability, and psychological distress.

METHODS

We conducted a parallel-group, quasi-randomized, double-blind, placebo-controlled trial in children and adolescents (ages 10-17) with migraine diagnosed per International Classification of Headache Disorders, 3rd edition criteria, recruited from pediatric neurology clinics at two academic medical centers. Of 57 participants allocated 1:1 to daily omega-3 PUFA supplementation (340 mg EPA + 510 mg DHA) or coconut oil placebo for 12 weeks, 44 completed the study and were analyzed. The primary outcome was change in whole-blood omega-3 PUFA index. Secondary outcomes included patient-reported measures of pain intensity, pain interference, migraine-related disability, and psychological distress. Exploratory outcomes included changes in omega-6/omega-3 and arachidonic acid/eicosapentaenoic acid (AA/EPA) ratios. Between-group differences were evaluated using ANCOVA adjusting for baseline values.

RESULTS

Omega-3 supplementation significantly altered lipid biomarker profiles. Compared with placebo, the intervention group demonstrated greater increases in omega-3 PUFA index (adjusted mean difference 1.64; 95% CI 0.94-2.35; p < 0.001) and greater reductions in omega-6/omega-3 ratio (-2.57; 95% CI -4.25 to -0.90; p = 0.003) and AA/EPA ratio (-13.52; 95% CI -21.55 to -5.49; p = 0.002), consistent with the increase in whole-blood omega-3 levels. No significant between-group differences were observed in patient-reported outcomes.

CONCLUSIONS

Omega-3 PUFA supplementation significantly altered lipid biomarker profiles in youth with migraine over 12 weeks, supporting a measurable whole-blood EPA + DHA response in this proof-of-concept trial. Future larger-scale trials with longer duration are needed to evaluate clinical effects.