Impact of Fatty Acid Supplementation on Migraine Outcomes: A Systematic Review and Meta-analysis

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Context: 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. Objective: The aim was to evaluate the efficacy of fatty acid supplementation on migraine clinical outcomes through a systematic review and meta-analysis. Data sources: This systematic review and meta-analysis was conducted using electronic databases including Medline, Scopus, Web of Science, and CINAHL from their inception up to October 7, 2024. Data extraction: Studies meeting the PICOS criteria were included: adults diagnosed with migraine, dietary supplementation with fatty acids, assessing migraine clinical outcomes, and only randomized controlled trials. Methodological quality and risk of bias were assessed independently by 2 reviewers using the Cochrane Risk of Bias 2 tool. Data analysis: Meta-analyses were conducted using Review Manager software. A random-effects model was applied to account for heterogeneity among studies. A standardized mean difference (SMD) of 0.2, 0.5, and 0.8 was interpreted as small, moderate, and large effects, respectively. Six randomized controlled trials, including 407 participants with chronic migraines, were analyzed. Interventions varied, including omega-3 supplementation with or without omega-6 restriction, lasting from 8 to 16 weeks, and 1 trial assessing alpha-lipoic acid. The overall risk of bias was assessed as low. The pooled analysis demonstrated significant reductions in headache intensity (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 HIT-6 score (SMD = -2.44; 95% CI: -4.13 to -0.76; P = .004). Conclusion: This meta-analysis provides moderate evidence that fatty acid supplementation, particularly omega-3, improves migraine clinical outcomes. Additional high-quality, randomized controlled trials are needed to confirm these findings, particularly for the promising effects of alpha-lipoic acid. Systematic review registration: PROSPERO registration no. CRD42024592084.

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García‑Pérez‑de‑Sevilla, G., & González‑de‑la‑Flor, Á. (2025). Impact of fatty acid supplementation on migraine outcomes: A systematic review and meta‑analysis. Nutrition Reviews, 83(9), 1621–1630. https://doi.org/10.1093/nutrit/nuae219

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