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Research Article: Association of altered plasma long-chain fatty acids with migraine-related disability: a clinical cross-sectional study

Date Published: 2026-07-15

Abstract:
The relationship between migraine and lipid metabolism, as well as its underlying mechanisms, remains poorly defined. In lipid metabolism, long-chain fatty acids (LCFAs) play a role in regulating cellular energy homeostasis and inflammation. Emerging evidence suggests a link between LCFAs and migraine pathophysiology. We investigated the association between altered plasma LCFAs and migraine-related disability. In this cross-sectional study, plasma samples and clinical data were collected from 118 individuals with migraine, comprising 79 with episodic migraine (EM) and 39 with chronic migraine (CM), and 118 matched healthy controls. Concentrations of 13 plasma LCFAs were quantified using targeted gas chromatography–mass spectrometry. Associations with migraine phenotype and clinical burden were assessed using regression and correlation analyses. Plasma levels of palmitic acid (C16:0), stearic acid (C18:0), and arachidonic acid (C20:4 n-6) were significantly higher in migraine patients than in controls, whereas docosahexaenoic acid (C22:6 n-3) levels were significantly lower. Multivariate logistic regression identified C16:0, C18:0, and C20:4 n-6 as independent correlates of migraine (AUC?=?0.912). Notably, higher levels of C16:0 and C20:4 n-6 were independently associated with with CM relative to EM (AUC?=?0.762), and positively correlated with monthly headache days, acute medication use, and disability scores. Our study showed that increased concentrations of plasma LCFAs, specifically C16:0, C18:0, and C20:4 n-6, were independently associated with migraine. C16:0 and C20:4 n-6 were associated with the burden of migraine-related disability. These findings suggest a potential role for the regulation of lipid metabolism in the management and prevention of migraine.

Introduction:
Migraine is a common neurological disorder characterized by recurrent episodes of unilateral throbbing headache ( 1 ). According to the 2021 Global Burden of Neurological Disorders Study, approximately 1.16 billion individuals (14.0% of the global population) are affected by migraine, making it the leading cause of disability among people aged 20–59?years ( 2 ). Current migraine diagnosis primarily relies on structured clinician-patient interviews based on established diagnostic criteria ( 1 , 3 ); however,…

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