The management of migraines remains a therapeutic challenge, especially when standard pharmacologic interventions produce limited relief or undesirable effects.
Among complementary agents, magnesium has emerged as a compound of clinical interest.
Far from being a simple dietary supplement, magnesium's influence on neurological excitability, vascular tone, and neurotransmitter regulation places it at the intersection of pathophysiology and targeted therapy for migraine prevention and relief.
Mechanistic Rationale: Magnesium and Neurovascular Homeostasis
Magnesium plays a critical role in stabilizing neuronal membranes, regulating calcium channels, and modulating glutamatergic transmission. These properties are especially relevant to migraine, a condition characterized by cortical hyperexcitability and altered vascular reactivity.
Studies suggest that hypomagnesemia may promote cortical spreading depression (CSD), a wave of neuronal and glial depolarization thought to trigger aura and migraine onset. Additionally, magnesium deficiency has been associated with elevated levels of substance P and serotonin, both implicated in migraine pathogenesis.
As noted by Dr. Alexander Mauskop, Director of the New York Headache Center, "Magnesium's role in blocking NMDA receptors and modulating CGRP release positions it as a logical adjunct in migraine control, especially in patients with identifiable deficiencies."
Clinical Evidence: Meta-Analyses and Guideline Insights
Recent randomized controlled trials (RCTs) and meta-analyses have strengthened the case for magnesium as a prophylactic agent. A 2023 meta-analysis published in Cephalalgia Reports reviewed 11 RCTs and concluded that magnesium supplementation (typically magnesium citrate or magnesium oxide, 400–600 mg/day) significantly reduced migraine frequency in adult populations.
Notably, the American Headache Society includes magnesium among its Level B recommendations for migraine prevention, stating that it is "probably effective", particularly in individuals with menstrual-related migraine or those seeking non-pharmacologic options.
Furthermore, a 2024 double-blind RCT conducted by Tehran University of Medical Sciences evaluated intravenous magnesium sulfate (1–2 g over 15 minutes) in emergency settings and reported a statistically significant reduction in pain intensity within 30 minutes, with minimal adverse effects.
Populations Most Likely to Benefit
While magnesium may not yield universal efficacy, subsets of migraine patients may derive particular benefit. These include:
- Individuals with low serum or intracellular magnesium levels (which are often undetected with standard serum tests).
- Pregnant patients, where magnesium offers a safer alternative to traditional anti-migraine medications.
- Patients with migraine with aura, where cortical excitability is a predominant feature.
For these cohorts, magnesium may serve both as a preventive and abortive option, depending on formulation and administration route.
Routes of Administration
Magnesium supplements remain the mainstay of long-term prophylaxis. However, bio-availability varies among formulations—magnesium oxide, though commonly prescribed, has lower absorption compared to magnesium glycinate or citrate, which are better tolerated gastrointestinally and more reliably absorbed.
In acute care settings, intravenous magnesium sulfate has shown promise in reducing migraine pain intensity and associated symptoms such as photophobia and nausea. This route may be particularly advantageous for patients with refractory migraine in emergency departments or infusion clinics.
Safety Profile and Monitoring
Magnesium is generally well-tolerated. The most frequent adverse effect is dose-related diarrhea, particularly with poorly absorbed salts. Toxicity is rare in patients with normal renal clearance, however, excessive dosing should be avoided. Periodic monitoring of magnesium levels—ideally via red blood cell (RBC) magnesium testing—may be appropriate in long-term use or high-dose therapy.
Limitations and Future Directions
While the current body of evidence is encouraging, more rigorously designed, large-scale trials are needed to define optimal dosing, duration, and patient selection criteria. Moreover, the interplay between magnesium and newer CGRP-targeted therapies presents a novel area of interest, particularly in combination protocols.
Biomarker-driven approaches to identify magnesium-responsive individuals could enhance precision medicine strategies in migraine care. Integration of magnesium status assessment into standard migraine workups may also improve personalization of treatment.
Magnesium should not be dismissed as merely an adjunctive or alternative remedy. When guided by clinical judgment and supported by patient-specific factors, it can provide substantial therapeutic value. In the context of rising demand for non-opioid, low-risk migraine management options, magnesium stands out as a neurotherapeutic agent with both mechanistic and empirical support.
