The Role of Magnesium in Migraine: A Comprehensive Science-Based Review
Introduction
Migraine is one of the most common and disabling neurological disorders worldwide, affecting over one billion people across different age groups. Characterized by recurrent attacks of moderate to severe headaches often accompanied by nausea, vomiting, and heightened sensitivity to light and sound, migraine significantly impacts quality of life and productivity. Despite extensive research, its exact pathophysiology remains complex and not fully understood. However, mounting evidence suggests that magnesium — an essential mineral involved in numerous physiological processes — plays a pivotal role in migraine development and treatment.
This article provides a science-based exploration of the role of magnesium in migraine, summarizing the evidence on deficiency, underlying mechanisms, and the effectiveness of supplementation in prevention and treatment.
Magnesium and the Human Body
Magnesium is the fourth most abundant cation in the body and a cofactor in more than 300 enzymatic reactions. It is crucial for ATP metabolism, ion channel regulation, nerve conduction, vascular tone, and neurotransmitter release. Because of its widespread role, even a mild deficiency can cause systemic dysfunctions, including those related to the nervous and vascular systems — both of which are implicated in migraine pathogenesis.
Magnesium Deficiency in Migraine Patients
Several studies show that individuals suffering from migraine often have reduced magnesium levels compared to healthy populations. These deficiencies have been identified in serum, plasma, cerebrospinal fluid, and within platelets.
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Clinical observations of deficiency: Research indicates that migraine patients frequently present with lower serum and intracellular magnesium levels (Karim et al., 2021). Similarly, magnesium concentration has been reported as an independent risk factor for migraine incidence (Assarzadegan et al., 2016).
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Dynamic changes during attacks: Some studies suggest that magnesium levels drop even further during migraine episodes, implying that deficiency may not just predispose but also actively trigger attacks (Masoud, 2003).
These findings strengthen the hypothesis that magnesium deficiency is closely tied to migraine pathophysiology.
Mechanisms Linking Magnesium to Migraine
Magnesium deficiency contributes to migraine susceptibility through several biological pathways:
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Cortical Spreading Depression (CSD): CSD is a wave of depolarization followed by suppressed brain activity, thought to underlie migraine aura and pain initiation. Magnesium helps stabilize neuronal membranes and inhibit glutamate release, thus reducing susceptibility to CSD (Rybicka et al., 2012).
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Neurotransmitter Modulation: Magnesium influences serotonin pathways and acts as a natural NMDA receptor antagonist. Deficiency leads to excessive neuronal excitability, glutamate activity, and increased release of inflammatory neuropeptides — all contributing to migraine attacks (Sun-Edelstein & Mauskop, 2009).
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Vascular Effects: Migraines have long been associated with vascular dysfunction. Magnesium regulates vascular tone by counteracting calcium-mediated vasoconstriction. Low magnesium may promote vasospasm and reduce cerebral blood flow, triggering headache onset.
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Inflammation and Oxidative Stress: Magnesium deficiency has been linked to systemic inflammation and increased oxidative stress, both of which play roles in migraine chronicity.
Together, these mechanisms explain why supplementation often reduces migraine burden in susceptible individuals.
Magnesium as a Preventive Treatment for Migraine
The use of magnesium supplementation for migraine prophylaxis has been investigated in multiple clinical trials.
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Oral supplementation studies: Oral magnesium supplementation has shown promising effects in reducing attack frequency, severity, and duration. For example, a comprehensive review concluded that oral magnesium is an effective, safe, and inexpensive preventive option (Sadeghi et al., 2015).
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Recent systematic evaluations: A recent 2025 review reinforced these conclusions, highlighting that magnesium supplementation reduces migraine incidence, especially in patients with documented deficiencies or menstrual-related migraines (DomÃnguez et al., 2025).
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Dosage considerations: Typical oral doses in clinical studies range from 300–600 mg/day of elemental magnesium. Forms such as magnesium citrate, glycinate, and aspartate are preferred due to superior absorption compared to oxide forms.
Intravenous Magnesium for Acute Migraine Treatment
While oral supplementation is useful for long-term prevention, intravenous (IV) magnesium sulfate has been studied for acute attacks.
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Rapid pain relief: IV magnesium can provide relief within 15 minutes in some patients, with effects lasting up to 24 hours. This was particularly noted in patients with low serum ionized magnesium levels during attacks (Mauskop et al., 1995).
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Variable effectiveness: Although beneficial in many cases, IV therapy is not universally effective. Some patients show no response, suggesting that magnesium therapy may be most effective for specific subgroups of migraineurs.
Safety, Tolerability, and Limitations
Magnesium is considered a safe and inexpensive treatment compared to many pharmacological options.
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Side effects: The most common side effect of oral supplementation is gastrointestinal upset, especially diarrhea. Using well-absorbed formulations at divided doses can minimize these effects (Sadeghi et al., 2015).
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Not universally effective: Some reviews caution against prescribing magnesium universally for all migraine patients, as not everyone responds equally. It may be best reserved for patients with documented low magnesium levels or certain subtypes such as menstrual migraines (Párdutz & Vécsei, 2012).
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Knowledge gaps: Despite positive findings, large-scale randomized controlled trials are still limited, and optimal dosing strategies remain unclear.
Conclusion
The evidence strongly suggests that magnesium deficiency is linked to migraine development and that supplementation can reduce attack frequency and severity in many patients. Mechanistically, magnesium modulates neuronal excitability, neurotransmission, vascular tone, and inflammatory pathways — all central to migraine pathogenesis. Oral supplementation appears particularly effective as a preventive strategy, while intravenous magnesium may benefit some patients during acute attacks. Although not a universal cure, magnesium offers a safe, affordable, and scientifically supported option for migraine management.