Migraine Prevention: The Evidence-Based Supplement Protocol

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Migraine prophylaxis is one of the rare conditions with formal AAN guideline-level evidence for supplements. The 2012 American Academy of Neurology evidence-based update assigned Level B (probably effective) to magnesium and riboflavin, and Level C to feverfew and CoQ10. Butterbur was originally Level B but has been dropped from clinical use due to pyrrolizidine alkaloid hepatotoxicity. The practical quartet is magnesium + riboflavin + CoQ10 + feverfew.

Magnesium, 400–600 mg Elemental Daily

Pooled trial data shows roughly 40% reduction in monthly migraine frequency at 400–600 mg elemental daily. Effect strongest in menstrual migraine and migraine-with-aura. See magnesium migraine piece.

Riboflavin (Vitamin B2), 400 mg Daily

Schoenen's 1998 trial established the 400 mg/day protocol. Pooled subsequent RCTs show ~50% reduction in monthly migraine days at 3-month follow-up. The mechanism centers on mitochondrial flavin coenzyme support. See riboflavin piece.

Coenzyme Q10, 100 mg Three Times Daily

The 2005 Sándor trial showed CoQ10 300 mg daily halved attack frequency versus placebo. Pooled meta-analyses have replicated the signal at lower effect sizes. See CoQ10 form piece.

Feverfew (Tanacetum parthenium), 100 mg Daily Standardized

The MIG-99 trial of stable feverfew extract showed modest but significant migraine frequency reduction. Use standardized 0.2–0.4% parthenolide extract. Taper rather than abruptly stop (rebound headache risk).

What NOT to Take

Avoid butterbur — the original Level B AAN recommendation was withdrawn due to PA hepatotoxicity. See note on the AAN migraine prevention stack. Avoid 5-HTP if on triptans/SSRIs — serotonin syndrome risk. Avoid melatonin without indication — useful for vestibular migraine and cyclical patterns but not chronic prevention. Skip CBD oil — thin migraine-specific evidence and supply quality issues.

How to Run the Protocol

Track migraine days in a diary for 1 month baseline. Add quartet components one at a time, 4 weeks apart, to attribute effect. Re-evaluate at 16 weeks of full quartet. A 50% reduction in monthly migraine days is the responder benchmark. Non-responders should be discussing CGRP-targeting therapy with a headache specialist. Sleep, hydration, and trigger identification often outperform any supplement intervention. See condition page and the related menstrual migraine protocol.