ABSTRACT

Background:
Migraine is a common, disabling neurological disorder affecting over one billion people worldwide, characterized by recurrent unilateral, pulsating headaches lasting 4-72 h. Caffeine, a widely consumed psychoactive alkaloid found in coffee, tea, and other beverages, is frequently implicated as both a trigger and a treatment for attacks.

Objectives:
We aim to comprehensively evaluate the association between caffeine exposure and migraine by integrating observational evidence with Mendelian Randomization (MR) studies.

Methods:
A comprehensive search was conducted through PubMed, Scopus, Web of Science, and the Cochrane Library till August 2025. We included primary studies assessing the impact of caffeine exposure on migraine risk.

Results:
19 studies (nine cross-sectional, seven MR, and three cohort) were included in our review. MR studies included over one million participants, while cross-sectional studies involved over 43,000 participants, and the cohort studies included 421 migraine cases. MR reflected lifelong genetic liability (population-level, chronic exposure) and associated with a reduced risk with overall odds ratio (OR) ranging from 0.53 to 0.71, with stronger associations reported in migraine with aura (ORs as low as 0.37-0.39). Observational studies captured short-term, acute effects and showed that abrupt withdrawal or acute excessive intake (≥ 3 drinks/day) can trigger attacks in some people (P = 0.024). While habitual moderate use was generally not linked to higher average migraine burden.

Conclusions:
Lifelong genetic liability to higher coffee/caffeine intake is associated with a reduced risk of migraine especially for migraines with aura. However, acute excessive intake or sudden changes in caffeine habits can trigger attacks in some people. More future large, well prospective cohorts and carefully designed MR studies are needed to confirm our results and clarify the precise impact of caffeine on migraine risk.

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