Hamdy Makhlouf1, Hamza Khelifa2, Fawaz Alfahmi3, Nada Abdelmohsen4, M.Yahya EL Arabawy5, Sohail Batarseh6, Anas Mansour7, Yasein Fadel Awadalla8
1Minia, Minia, Badie Alzaman street, Faculty of Medicine, Minia University, Minia, Egypt, 2Faculty of Medicine, University of Oran, 1 Ahmed Ben Bella, Oran, Algeria, 3College of Medicine, Taif University, Taif, Saudi Arabia, 4Faculty of physical therapy, South Valley University, Qena, Egypt., 5Faculty of medicine Al-Azhar university, Cairo, Egypt, 6Jordan University Of science and Technology, 7Faculty of Medicine, Al-Azhar University, Cairo, Egypt., 8Faculty of Science, Al-Azhar University, Cairo, Egypt
Objective:
We aim to comprehensively evaluate the association between caffeine exposure and migraine by integrating observational evidence with Mendelian Randomization (MR) studies.
Background:
Migraine is a common, disabling neurological disorder affecting over one billion people worldwide, characterized by recurrent unilateral, pulsating headaches lasting 4–72 hours. 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.
Design/Methods:
A comprehensive search was conducted through PubMed, Scopus, Web of Science, and the Cochrane Library till August 2025, to include primary studies on migraine patients exposed to caffeine. We studied association of caffeine (either acute or chronic intake) with the risk of migraine using odds ratios (ORs).
Results:
Ten studies (7 MR studies and 3 cohorts) were included in our review. MR reflects lifelong genetic liability (population-level, chronic exposure) and shows protective effects with overall 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 cohorts capture short-term, acute effects and show that high or sudden increases (≥3 drinks/day) can trigger attacks in some people (P = 0.024), while habitual moderate use (0–3/4 cups/day) is 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 migraine with aura. However, acute large doses or sudden changes in caffeine can trigger attacks in some people. Future studies should use non-overlapping, diverse cohorts and quantify dose- and timing-specific effects.
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