Meta-Analysis Reveals Fatty Acid Supplementation Linked to Migraine Symptom Improvement

Guillermo García Pérez de Sevilla, PhD

(Credit: European University of Madrid)

Newly published in Nutrition Reviews, a meta-analysis of randomized controlled trials revealed that fatty acid supplementation improved clinical outcomes in individuals with migraine. Overall, the findings provided moderate evidence that support the use of omega-3 fatty acids for migraine prophylaxis.¹

The analysis included 6 randomized controlled trials comprising 407 participants with chronic migraine, assessing the effects of fatty acid supplementation over 8 to 16 weeks. The overall risk of bias across studies was assessed as low, and the pooled data showed significant reductions in headache intensity (standardized mean difference [SMD] = -1.77; 95% CI, -3.32 to -0.21; P = .03), headache duration (SMD = -0.77; 95% CI, -1.05 to -0.50; P < .00001), headache frequency (SMD = -1.91; 95% CI, -2.61 to -1.21; P < .00001), and Headache Impact Test-6 (HIT-6) scores (SMD = -2.44; 95% CI, -4.13 to -0.76; P = .004).

“Migraines are a prevalent neurological condition that significantly impacts the quality of life. Although narrative reviews and clinical trials suggest the potential effects of fatty acid supplementation as a promising approach for migraine prophylaxis, the findings remain inconsistent,” coauthors Guillermo García Pérez de Sevilla, PhD, professor of physical activity and sports sciences, and Ángel González de la Flor, PhD, professor of physiotherapy, both from at the European University of Madrid, wrote.¹

Researchers performed the systematic review and meta-analysis using Medline, Scopus, Web of Science, and CINAHL databases up to October 7, 2024. Authors noted that only randomized controlled trials that included adults with migraine receiving fatty acid supplementation were selected, following strict PICOS criteria. Additionally, the study had methodological quality and risk of bias independently assessed by 2 reviewers using the Cochrane Risk of Bias 2 tool.

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All told, the interventions varied across studies, with most focusing on omega-3 supplementation, sometimes paired with omega-6 restriction, and 1 trial investigating the effects of alpha-lipoic acid. Investigators noted that the use of a random-effects model accounted for heterogeneity among studies, with SMDs interpreted as small, moderate, or large effects.

Despite these encouraging results, the researchers emphasized that additional high-quality randomized controlled trials may be needed to confirm the efficacy of fatty acid supplementation for migraine, particularly for alpha-lipoic acid, which showed promising but preliminary outcomes. This study builds on prior findings where in a separate meta-analysis, results showed that although omega-3 fatty acids might not have affected migraine frequency or severity, they significantly shorted migraine attack duration.² The analysis included 13 randomized controlled trials, of which 5, 2, and 3 trials met eligibility criteria to assess omega-3’s impact on migraine frequency, duration, and severity, respectively.

Results indicated no significant effect on migraine frequency (weighted mean difference [WMD] = -0.20; 95% CI, -0.67 to 0.27; P = 0.401) or severity (SMD = -0.59; 95% CI, -1.85 to 0.66; P = 0.35), but a notable reduction in the duration of migraine attacks by approximately 3.44 hours (WMD = -3.44; 95% CI, -5.70 to -1.19; P = 0.003). Meta-regression analyses also explored potential sources of heterogeneity. Low heterogeneity was observed for migraine frequency (I² = 4.6%; P = 0.380) and duration (I² = 0.0%; P = 0.926), whereas high heterogeneity was seen for severity outcomes (I² = 88.8%; P = 0.000).

Despite the mixed findings, the prior analysis supports that omega-3 supplementation could significantly reduce the duration of migraine attacks. However, researchers noted that further randomized controlled trials with robust methodological design and larger sample sizes may be necessary to confirm these results.

REFERENCES
1. García-Pérez-de-Sevilla G, González-de-la-Flor Á. Impact of Fatty Acid Supplementation on Migraine Outcomes: A Systematic Review and Meta-analysis. Nutr Rev. Published online January 17, 2025. doi:10.1093/nutrit/nuae219
2. Maghsoumi-Norouzabad L, Mansoori A, Abed R, Shishehbor F. Effects of omega-3 fatty acids on the frequency, severity, and duration of migraine attacks: A systematic review and meta-analysis of randomized controlled trials. Nutr Neurosci. 2018;21(9):614-623. doi:10.1080/1028415X.2017.1344371