Investigating the causal association between coffee and migraine using Mendelian randomization analysis

<b>Background</b>: Migraine is a chronic neurological disorder influenced by various risk factors, including inadequate medication, anxiety, sleep disorders, depression, and stress-inducing events. Coffee is well-known for its diverse bioactive properties and may help relieve acute migraine symptoms; however, stopping long-term coffee consumption can unexpectedly trigger migraines. While some migraine sufferers view caffeine as a potential trigger, research suggests it may also have preventive effects. The complex physiological and pharmacological mechanisms behind coffee and its active components are not fully understood.  <b>Objective</b>: This study aims to clarify the relationship between coffee consumption and its components and the risk of developing migraines. <b>Methods</b>: We conducted a Mendelian randomization (MR) analysis, using genetic variants as proxies for exposure to reduce confounding factors and biases. <b>Results</b>: Our results show a significant inverse relationship between coffee intake and migraine risk, consistent with previous epidemiological studies that indicate coffee may protect against headache disorders. The MR analysis also found that 7-methylxanthine is linked to a lower risk of migraines, while caffeic acid sulfate is associated with a higher risk. Sensitivity analyses showed no heterogeneity in SNP selection for all components, except for trigonelline, and both MR-Egger and MR-PRESSO tests did not indicate horizontal pleiotropy or outliers. Our research highlights the significant impact of coffee and its components on migraine risk, providing valuable dietary recommendations. The protective effect of coffee may be closely related to adenosine receptor antagonism, which warrants further investigation to better understand the underlying mechanisms.