Dosing effects of omega-3 fatty acid interventions in adults with migraine: Systematic review and meta-analysis of randomized clinical trials

Alarcon-Ruiz C.A.; Goicochea-Romero P.A.; Jiménez-Mozo F.; Mayta-Tovalino F.; Pacherres-López A.; Runzer-Colmenares F.M.; Peres M.F.P. · Cephalalgia Reports (2026) · DOI: 10.1177/25158163261454627

Resumen

Objective: To evaluate the clinical effects and safety of omega-3 fatty acid dietary and supplemental interventions for the prevention of migraine in adults, considering subgroups according to dosing and migraine subtypes. Background: Migraine is a highly prevalent and disabling neurological disorder worldwide, with multifactorial pathophysiology and limited understanding of its underlying biological mechanisms. Given the role of diet in migraine modulation and the involvement of omega-3 fatty acids in pain-related inflammatory pathways, their therapeutic potential as migraine prophylactic remains to be clarified. Methods: A systematic search in Cochrane Central-Ovid, Scopus, Embase, and Web of Science (November 2025) identified randomized controlled trials (RCTs) on omega-3 or omega-6 supplementation in adults with migraine. The primary outcomes included monthly headache days, daily headache hours, pain intensity, headache impact (HIT-6 and MIDAS), and adverse events. A random-effects model estimated the mean differences (MD) with 95% confidence intervals (CI), and the certainty of evidence was assessed using GRADE. Results: Ten RCTs on omega-3 interventions were found, with two evaluating omega-3-rich diets and others using doses of 1–6 g/day. No studies assessed omega-6. Overall, omega-3 interventions reduced daily headache hours (MD:1.74, 95% CI: −2.29 to −1.19 and monthly headache days (MD:-2.39 days; 95% CI: −3.78 to −1.00) but did not reduce pain intensity. It improved MIDAS (MD: −12.88, 95% CI: −18.36 to −7.40) and HIT-6 (MD:-2.94; 95% CI: −4.32 to −1.56). Digestive adverse effects were reported with 6 g/day. The certainty of evidence was low or very low due to bias, imprecision, and inconsistency. The omega-3 diet improved the chronic migraine frequency but not the quality of life. Capsules (1 to 1.5 g/day) had no effect, while 2 g/day slightly improved headaches and HIT-6. However, in episodic migraine, 1 to 2.5 gr./day improved the frequency and quality of life, but 6 gr./day had no effect. Conclusion: Omega-3 interventions, particularly structured high-omega-3, low-omega-6 dietary programs and moderate-dose supplementation, may modestly reduce migraine frequency and disability, with the greatest benefit observed in episodic migraine. Further large, high-quality RCTs are warranted to confirm these findings and clarify the optimal dosing strategies. Trial Registration: PROSPERO (CRD42022296249). © The Author(s) 2026. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).

Instituciones: Universidad Peruana Cayetano Heredia; Universidad Científica del Sur; Universidad de San Martín de Porres; Universidad San Ignacio de Loyola