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Magnesium For Migraines: An Intervention To Consider

Migraines are characterized as excruciatingly painful headaches commonly accompanied by symptoms of nausea and/or sensory hypersensitivity (such as to light or sound).  A small percentage of individuals with migraines are able to prevent future migraine attacks with strategic lifestyle changes such as: reducing stress, adhering to a strict sleep schedule, and/or dietary adjustments.  However, many migraine sufferers are unable to derive even an inkling of symptomatic relief from recommended lifestyle alterations.

Among those diagnosed with chronic migraine, medical professionals generally prescribe abortive agents (e.g. a triptan) that can be administered on an “as-needed” basis to attenuate the severity of migraine attacks.  Furthermore, it is common for professionals to simultaneously prescribe a prophylactic agent (e.g. amitriptyline for migraines) to reduce the future occurrence of migraine headaches.  That said, not every patient responds well to conventional migraine prophylactic pharmacology.

Although pharmacological options are considered clinically effective in accordance with FDA testing, not all patients attain sufficient therapeutic benefit and/or are able to tolerate side effects of pharmaceuticals.  For this reason, an appealing alternative, non-pharmacological migraine prophylactic is magnesium.  Since individuals with migraine headaches often exhibit abnormally low levels of magnesium, its supplementation is thought to prevent migraine attacks.

How Magnesium May Prevent or Treat Migraines (Mechanisms of Action)

The specific mechanisms by which magnesium supplementation prevents migraines remains unclear.  That said, magnesium may yield therapeutic benefit by: inhibiting cortical spreading depression, modulating serotonin, decreasing excitability of NMDA receptors, and/or reducing calcitonin gene-related peptide (CGRP).  Abnormally low levels of magnesium are understood to increase risk of migraine attacks, and for many individuals with magnesium deficits, increasing its intake (via diet or supplementation) can reduce frequency of attacks by over 40%.

Calcitonin Gene-Related Peptide (CGRP): A biomarker commonly assessed among migraine sufferers is CGRP or calcitonin gene-related peptide.  A report by D’Andrea et al. (2012) entitled “Pathogenesis of Migraine: Role of Neuromodulators” implies that abnormalities in synthesis of neurotransmitters (e.g. norepinephrine and dopamine) as well as neuromodulators (e.g. tyramine, octopamine, syneprhine, etc.), may facilitate activation of the trigeminal system to upregulate levels of CGRP.

Increased levels of CGRP is understood to provoke neurogenic inflammation which triggers migraine attacks via cortical spreading depression.  A study conducted by Myrdal et al. (1994) assessed the effect of magnesium sulphate infusions on CGRP concentrations.  It was discovered that infusions of magnesium sulphate significantly decreased CGRP from 15.5 pmol to 10 pmol.

Since it is understood that magnesium can ameliorate neurotransmitter and/or neuromodulator abnormalities (to a certain extent), the trigeminal system may be less likely to produce CGRP.  Additionally, if the trigeminal system stimulates the production of CGRP, it appears as though magnesium infusions are able to reduce the amount of CGRP in circulation.  Reducing the amount of circulating CGRP may inhibit cortical spreading depression and ultimately a migraine attack.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/22671857
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/7820978

C-Reactive Protein (CRP): Magnesium depletion is associated with increases in inflammatory biomarkers such as C-reactive protein (CRP).  A study by Nielsen (2014) discovered that intake of less than 250 mg/day of magnesium, as well as serum concentrations of magnesium lower than 0.75 mmol/l is associated with elevated C-reactive protein.  Contrarily, sufficient magnesium intake and serum magnesium concentrations is able to attenuate C-reactive protein elevations.

Researchers Lippi et al. (2014) investigated whether C-reactive protein may play a role in the pathogenesis of migraines.  They scoured 17 studies that assessed links between CRP and migraines, and pooled the data.  Following pooling of the data, it was noted that individuals with migraine attacks had significantly greater concentrations of CRP [by 1.12 mg/L] compared to non-migraine controls.

Based on the evidence, we know that C-reactive protein increases as a result of magnesium deficits, as well as that C-reactive protein is high among migraine sufferers.  It could be that C-reactive protein directly causes migraines in certain individuals by inducing neurogenic inflammation.  Ensuring that an individual consumes adequate magnesium may be helpful in decreasing CRP-induced neurogenic inflammation to provoke migraines.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/25023192
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/24717337
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/9415506

Cortical spreading depression: A chief mode by which magnesium may prevent migraines among sufferers is via inhibition of cortical spreading depression.  Cortical spreading depression (CSD) is defined as an acute wave of neuroelectrical hyperactivity succeeded by an acute wave of neuroelectrical hypoactivity.  The hyperactivity is characterized by constriction of blood vessels, and the hypoactivity that follows triggers vasodilation or enlargement of blood vessels.

Blood vessel enlargement leads to increased blood flow and facilitates pain and/or throbbing implicated in migraines.  A deficiency in magnesium (Mg2+) is understood to increase neuronal excitability via glutamate receptors, thereby causing cortical spreading depression and migraine attacks.  Increasing magnesium levels within a normative, healthy range is though tot decrease excitability of glutamate receptors, ultimately raising the threshold for cortical spreading depression and preventing migraines.

NMDA receptor modulation: Evidence indicates that magnesium (Mg2+) ions are able to penetrate the NMDA receptor pore with tight binding to the receptor sites.  As a result of their penetration and tight binding to NMDA receptors, a greater amount of glutamate is required to displace the Mg2+ ions from these sites.  In other words, it takes more stimulation than usual to provoke cortical spreading depression through NMDA receptors; the magnesium ions essentially act as a buffer to prevent the onset of cortical spreading depression – and migraines.

What’s more, it appears as though the presence of magnesium ions augments the blockade of NMDA receptor sites induced by various cations.  Researchers Nikolaev et al. (2012) discovered that NMDA receptor channel blockers (-30 mV) were enhanced by 1.5-fold to 5-fold with the presence of magnesium ions (compared to a lack thereof).  This suggests that individuals with deficits in magnesium may be inherently more prone to overstimulation of NMDA receptors, leading to cortical spreading depression, as well as migraines.

In summary, magnesium is necessary for maximal NMDA receptor antagonism and appears to reduce likelihood of glutamatergic release from NMDA receptor sites.  A reduction in glutamate release from NMDA receptors is capable of decreasing pain signaling to the trigeminal nucleus complex.  Not only may magnesium act as a prophylactic via the NMDA receptors, but it may reduce the perceived pain of occurring migraines.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/22261381
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/9577281
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/8835616
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/19168292

Serotonergic modulation: Research has shown that many individuals with migraines exhibit abnormalities in the neurotransmission of serotonin.  Although serotonergic abnormalities among migraine sufferers may be nothing more than a non-causative correlation, it is understood that many effective migraine prophylactics (e.g. tricyclic antidepressants) function primarily by inhibiting the reuptake of serotonin.  Therefore, it is relatively shortsighted to dismiss the role of serotonergic abnormalities in the pathogenesis of migraines.

Sufficient dietary intake of magnesium is understood to increase serotonin levels among persons with underlying deficits.  Increasing concentrations of serotonin may play an important role in the prevention of migraines, possibly by enhancing the efficiency of serotonergic signaling.  It could also be that magnesium acts similarly to abortive agents (e.g. triptans) by activating serotonin receptors on the trigeminal nerve and/or cranial vessels.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/19621270

Benefits of Magnesium for Migraines (Possibilities)

Below is a list of benefits associated with using magnesium as an intervention for migraines.  Perhaps the most well-documented benefit of magnesium among migraine sufferers is its prophylactic efficacy; it is highly effective as a migraine preventative among those with underlying magnesium deficiencies.  Other advantages associated with using magnesium as an antimigraine agent include: headache pain reduction, holistic health improvements (via correction of a deficiency), minimal side effects, and safety.

  • Acute abortive therapy: Although magnesium gets the most attention from migraine patients for its usefulness as a migraine prophylactic, several studies have highlighted its efficacy as an abortive therapy. In other words, administration of magnesium during a migraine attack can attenuate symptoms rapidly – similar to first-line agents (e.g. triptans).  One study (discussed above) noted that migraine pain was completely eliminated within 15 minutes of receiving magnesium sulfate (MgSO4) infusions in 80% of migraine patients.  What’s more, migraine pain and/or recurring migraines remain under control for a full 24-hour period in over 50% of patients receiving magnesium sulfate infusions.
  • Adjunctive option: The fact that magnesium is considered safe and has few contraindications makes it an appealing adjunct among migraine sufferers. Some individuals may like the idea of taking magnesium as a migraine prophylactic or abortive therapy, but may still wish to utilize conventional antimigraine drugs if needed.  In some cases, a medical professional may recommend taking magnesium along with another drug for superior migraine relief than would’ve been attained from either intervention as a standalone.
  • All ages: While most studies tested magnesium’s antimigraine efficacy on adults (ages 18 to 65), other research has tested it among pediatrics with recurrent headaches. In one study among pediatrics, administration of magnesium oxide was able to reduce headache severity and reduce number of headache days (compared to the pre-treatment baseline).  This suggests that magnesium may be a helpful intervention among all headache/migraine sufferers – regardless of age.
  • Alternative intervention: Magnesium serves as a viable alternative migraine prophylactic for those who aren’t responding well to other treatments. Not everyone responds to first-line and second-line prophylactics nor abortive therapies.  For non-responders, magnesium warrants consideration as an alternative intervention.  In some cases, magnesium may be a superior option to conventional treatments – especially if a magnesium deficiency was the chief culprit for migraines.
  • Combination treatment: Some studies have assessed the efficacy of magnesium as part of a supplemental regimen along with Riboflavin (vitamin B2), CoQ10 (or Ubiquinol), and sometimes, fish oil. You may want to discuss the safety these supplements with your doctor and consider that the benefit of a combination treatment (incorporating magnesium) may be highly effective for the prevention of migraines.  Since mitochondrial dysfunction and low magnesium are implicated in migraine attacks, it is likely that a combined treatment is more effective than standalone magnesium.
  • Corrects deficiency: A subset of migraine patients may experience migraines solely because they aren’t consuming enough magnesium. Some research suggests that magnesium deficiency is an epidemic – affecting nearly 70% of all Americans.  Perhaps more alarming is the fact that around 20% of all Americans don’t even consume half of the recommended daily intake intake of magnesium.  In addition to causing migraine attacks, magnesium deficiencies can cause anxiety, confusion, fatigue, memory problems, and more.  Correcting the deficiency may significantly improve an individual’s overall health, especially neurological function.
  • Efficacy: Though administration of magnesium is clearly not effective for all individuals with migraines, many derive benefit from its supplementation. Studies have been able to prove that magnesium supplementation is most effective among migraine sufferers with an underlying magnesium deficiency.  Magnesium is not only an effective migraine prophylactic, it appears to function as an effective abortive therapy, reduce secondary symptoms (nausea and sensory sensitivities), and minimize global disease burden.
  • Headache treatment: Those with migraines may suffer from comorbid general headaches or be misdiagnosed with migraines as a result of certain types of headaches such as cluster headaches or chronic tension-type headaches. Research has shown that headache suffers, especially those with cluster headaches, exhibit magnesium deficits.  Regular administration of magnesium appears to provide significant headache relief.
  • Low-cost: Magnesium supplementation is generally very low cost, especially when compared to newer antimigraine pharmaceuticals. Some magnesium supplements only cost around 11-cents per serving, making it an affordable option for those who don’t have good insurance and/or are struggling financially.  Furthermore, magnesium is easier to attain than a pharmaceutical in that users don’t need to wait for a prescription to be filled (and refilled between doses), they can simply purchase it over-the-counter.
  • Migraine subtypes: There are two types of migraines diagnosed including: migraine with aura (“classic migraine”) and migraine without aura (“common migraine”). Administration of magnesium appears effective for the prophylaxis of both types of migraines.  That said, some believe that magnesium may be most effective for those with classic migraine due to the fact that “aura” is associated with cortical spreading depression.  Magnesium interferes with the onset of cortical spreading depression and ultimately blunts the “aura” (visual and/or sensory disturbances).  Additionally, magnesium appears effective for those suffering from premenstrual or menstrual-related migraines.
  • Minimal side effects: Many migraine patients find that they’re unable to tolerate side effects of various abortive agents (e.g. triptans) or prophylactics (e.g. TCAs). Common side effects of pharmaceutical drugs include: brain fog, cognitive deficits, dizziness, fatigue, somnolence, etc.  The fact that magnesium is unlikely to cause unwanted side effects or severe adverse reactions makes it an attractive intervention for migraines.
  • Non-pharmacological: The fact that magnesium is a non-pharmacological antimigraine intervention makes it an appealing option for many individuals with migraines. There are several reasons why someone may prefer to use magnesium over standard pharmacology including: they are magnesium deficient (the deficiency could be the root cause of migraines), they’re unable to tolerate side effects of conventional antimigraine drugs, and/or they’re taking other medications that are contraindicated with conventional antimigraine agents – but not magnesium.  If you wish to avoid pharmaceuticals and treat migraines with a natural option, magnesium may be preferred.
  • Pain reduction: Certain migraine prophylactics may reduce the number of migraine attacks per month, but may fail to attenuate the pain that occurs during a migraine attack. Research suggests that magnesium significantly reduces migraine-related pain (e.g. head throbbing) compared to a placebo.  This pain reduction may stem from magnesium’s inhibition of pain-transmitting neurochemicals such as glutamate and substance P.  Since pain is typically the most debilitating aspect of a migraine attack, the fact that magnesium reduces this pain may allow a person to remain fully functional and bypass the need for abortive medication.
  • Prophylaxis: Arguably the biggest benefit associated with using magnesium for migraines is that it serves as a prophylactic – especially among those with deficiencies. Adequate magnesium intake appears to reduce the number of migraine attacks per month.  There are numerous mechanisms by which magnesium provides prophylactic benefit, arguably the most significant is its ability to blunt stimulation of NMDA receptors – ultimately raising the threshold for cortical spreading depression.
  • Safety: Most professionals consider magnesium to be an extremely safe supplement when taken at normative dosages. Although individuals with migraines may require a slightly higher initial dose (due to a magnesium deficiency) compared to those without migraines, once underlying deficiencies are corrected, patients may be able to scale back the dosing.  In the literature, there were no major safety concerns reported among those taking magnesium (even at high doses) for migraines.  It is also considered fairly safe to take during pregnancy, whereas pharmaceutical agents are not.
  • Secondary symptoms: Though the most common symptom migraine patients complain about is a throbbing headache or head pain, migraine attacks often provoke secondary symptoms. Examples of common secondary symptoms include extreme nausea (sometimes to the extent of provoking vomiting) and hypersensitivity to lights and/or sounds.  Some research noted that magnesium sulfate infusions fully mitigated nausea and sensory hypersensitivity during an attack.

Drawbacks of Magnesium for Migraines (Possibilities)

Not everyone with migraines responds well to magnesium supplementation.  Those without an underlying magnesium deficiency may not derive any therapeutic benefit from taking magnesium.  Others may find that magnesium only provides modest benefit and causes numerous unwanted side effects such as diarrhea and/or gastrointestinal distress.

  • Adverse effects: Those taking too much magnesium may experience adverse effects such as: coma, confusion, hypotension (low blood pressure), irregular heartbeat, slowed breathing, and possibly death. Understand that adverse effects may be more debilitating than the migraine that an individual is treating with magnesium.  These adverse effects may be especially pronounced among patients with renal impairment.
  • Contraindications: Although magnesium is often safe to take along with a pharmaceutical drug, it is not devoid of contraindications. In some cases, magnesium can interact with antibiotics, diuretics, heart medications, and muscle relaxers.  Magnesium can also alter the pharmacokinetics of other medications and/or interfere with their absorption.  For this reason, it is necessary to confirm the safety of magnesium supplementation with your doctor prior to taking it.
  • Questionable efficacy: Based on the available literature, some would question whether magnesium is legitimately effective as an antimigraine agent. Clearly it doesn’t work for everyone, and while some studies demonstrate its efficacy compared to a placebo, others have failed to find any benefit.  Furthermore, it may be less effective than other non-pharmacological interventions (e.g. Riboflavin) and its therapeutic value is less understood than conventional antimigraine pharmacology.
  • Side effects: While some individuals may not experience severe adverse reactions from magnesium supplementation such as heartbeat changes, mental confusion, or slowed breathing – certain users may report unwanted side effects. In trials of those taking magnesium for migraines, some patients reported diarrhea, gastrointestinal distress, and stomach aches.
  • Side effects from magnesium can include lower blood pressure and diarrhea. Magnesium can interact with medications, including heart medications, diuretics or water pills, some antibiotics, and muscle relaxers.
  • Too much magnesium: The recommended daily intake of magnesium for men is 400-420 mg/day and for women is 310-320 mg/day. Magnesium can be attained via dietary sources such as green leafy vegetables, unrefined grains, nuts, and legumes.  Those taking magnesium for migraines often exceed the recommended daily intake with supplements.  Supplementation of magnesium at dosages up to 350 mg/day is considered safe for most adults.  However, many migraine protocols have patients taking up to 600 mg/day.  If patients continue taking 600 mg/day over a long-term, they may suffer from deleterious health complications resulting from excessive magnesium.

Magnesium for Migraines (Review of Research)

To determine whether any intervention such as magnesium is effective for the management of migraines, it is necessary to assess the existing scientific literature.  As of 2012, the American Headache Society and American Academy of Neurology reviewed studies that investigated magnesium supplementation as a migraine prophylactic.  Authors concluded that magnesium as a migraine prophylactic warrants “Level B” classification – indicating that it is likely efficacious, safe, and unlikely to cause adverse effects.  Below is a brief synopsis of all publications dating from late 1980s to 2015 that investigated magnesium as a migraine prophylactic.

2015Improvement of migraine symptoms with a proprietary supplement containing riboflavin, magnesium and Q10: a randomized, placebo-controlled, double-blind, multicenter trial.

A study by Gaul et al. (2015) assessed the therapeutic efficacy of a supplemental medley of Riboflavin (vitamin B2), Magnesium, and CoQ10 for prophylaxis of migraines.  Prior research documented decreased (or deficient) levels of micronutrients such as Riboflavin, Magnesium, and CoQ10 among migraine sufferers within the brain and plasma.  Based on these findings, one would hypothesize that increasing Riboflavin, Magnesium, and/or CoQ10 may decrease the occurrence of migraines.

Mitochondria or cellular powerhouses require adequate Riboflavin, Magnesium, and CoQ10 to produce sufficient energy.  When levels of these micronutrients are low, mitochondrial energy production decreases, which may lead to migraines.  Researchers outline the role of each micronutrient in the pathogenesis of migraines, stating that Magnesium is important for vasoconstriction, platelet inhibition, serotonin synthesis, and antagonism of NMDA receptors.

They note that magnesium is also an important cofactor for ATP-synthase function, which generates ATP (adenosine triphosphate).  Without Riboflavin, flavin-mononucleotide (FMN) and flavin-adenine-dinucleotide (FAD) aren’t sufficiently synthesized.  Lack of FMN and FAD leads to dysfunctional transport of electrons in mitochondrial membranes.

Coenzyme Q10 (CoQ10) is synthesized endogenously by the body from phenylalanine and tyrosine.  Without enough CoQ10, electron transport is reduced and cellular processes become less efficient.  Since migraine sufferers exhibit mitochondrial abnormalities and reduction in quantities of these micronutrients, researchers sought to test the efficacy of their administration for the treatment of migraines.

Testing of non-pharmacological interventions was also important due to the fact that many patients refuse conventional pharmacology and/or are unable to cope with side effects.  For the study, researchers recruited 130 adults that had been formally diagnosed with migraines (each experienced at least 3+ migraine attacks per month).  All participants were assigned at random to receive either: Dolovent® (600 mg magnesium, 400 mg riboflavin, 150 mg CoQ10) or a placebo – for a total of 3 months.

Prior to treatment, the 130 participants were monitored for 4 months to assess baseline migraine severity.  Following the 3-month treatment term, patients were reevaluated for number of days with migraine, severity of migraine-related pain, disease burden, and subjective evaluation of treatment efficacy.  Results indicated that number of migraine days per month declined from 6.2 (baseline) to 4.4 (post-treatment) with the Dolovent®, whereas it only declined from 6.2 (baseline) to 5.2 (post-treatment) with the placebo.

Severity of migraine pain had also significantly decreased among the Dolovent® recipients compared to the placebo.  Scores of migraine disease burden decreased by 4.8 points among the Dolovent® group compared to just 2 points in the placebo group (as measured by the HIT-6 questionnaire).  Additionally, subjective evaluations of treatment efficacy provided by patients suggested that Dolovent® was superior to the placebo.

Although the Dolovent® intervention was significantly more effective than a placebo based on measures of migraine severity, disease burden, and patient-perceived efficacy – it was not significantly more effective in reducing the number of migraine days per month compared to the placebo.  Researchers believe that the study may have been underpowered, ultimately yielding lack of statistical significance on the primary endpoint (number of headache days per month) compared to the placebo.  The fact that results indicate that Dolovent® is better than a placebo for attenuating migraine severity plus disease burden – signifies its preliminary usefulness as a non-pharmacological migraine intervention.

Few adverse effects were reported among Dolovent® users, but included: diarrhea and stomach aches; likely from high doses of magnesium.  Further research may be warranted to determine the efficacy of this combination in larger samples, as well as pinpoint whether a component (or components) of the supplement (e.g. CoQ10) may be more therapeutic than the others (e.g. Magnesium and Riboflavin).  Nonetheless, the combination of magnesium (600 mg), riboflavin (400 mg), and CoQ10 (150 mg) appear helpful for the management of migraines.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/25916335

2012: Why all migraine patients should be treated with magnesium.

Researchers Mauskop and Varughese (2012) published a report recommending that all migraine patients should be administered magnesium.  They noted that adequate intake of magnesium is critical for a host of intracellular processes.  It was also mentioned that deficits in magnesium could result in cortical spreading depression, platelet hyperaggregation, and altered synthesis of neurotransmitters – each of which may induce migraines.

In this report, researchers presented the fact that migraine sufferers often are deficient in magnesium compared to healthy non-migraine controls.  Additionally, they conferred that while “mixed results” (in terms of efficacy) were apparent in double-blind, placebo-controlled studies – these mixed results resulted from the inclusion of non-deficient and deficient migraine patients.  They imply that among magnesium deficient patients, efficacy of magnesium as a prophylactic would’ve been proven.

Since blood tests are incapable of measuring total bodily magnesium (over 60% of magnesium accumulates within bones) and brain magnesium, it is nearly impossible to determine whether someone is legitimately deficient or not.  More problematic is the fact that some migraine sufferers may be consuming adequate magnesium, but are unable to properly absorb it as a result of genetic conditions (e.g. renal magnesium wasting) or high stress.  That said, it appears as though oral and intravenous forms of magnesium are readily available, safe, and cheap for migraine suffers.

It is mentioned that among individuals with magnesium deficits, supplementation will likely be very effective for preventing future migraines.  Authors estimate that approximately half of all migraine sufferers may have low magnesium and that currently-available blood tests are useless for determining whether someone is likely to benefit from its supplementation.  In conclusion, Mauskop and Varughese recommend that all migraine sufferers should test the efficacy of oral magnesium supplementation.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/22426836

2011: Relation between serum magnesium level and migraine attacks.

A study by Talebi et al. (2011) assessed the relationship between serum magnesium concentrations and migraine attacks.  For the study, researchers assessed a total of 140 migraine patients at Tabriz University of Medical Sciences (in Iran) from January to December 2007.  They compared serum magnesium concentrations among the 140 migraine patients to an equal number (140) of healthy controls.

It is important to note that none of the participants in the study were taking magnesium supplements.  Results indicated that serum magnesium concentrations were markedly reduced among those with migraines compared to the healthy controls.  On average, the individuals with migraines exhibited serum magnesium levels of 26.14, whereas healthy controls exhibited levels of 31.09.

Although there were no significant differences in magnesium concentrations among migraine sufferers with aura compared to those without – there was a relationship between serum magnesium and headache frequency.  Researchers concluded that serum magnesium concentrations are significantly lower among those with migraines compared to non-migraine patients.  Evidence supports the administration of magnesium for migraine prophylaxis and management.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/21983373

2009: Role of magnesium in the pathogenesis and treatment of migraine.

Sun-Edelstein and Mauskop (2009) analyzed the influence of magnesium in the onset of migraines.  Researchers noted that magnesium is implicated in an array of cellular functions and is a critically important intracellular element.  They speculated that magnesium deficiencies might induce cortical spreading depression, modulate neurotransmission, and facilitate hyperaggregation of platelets – all of which could prompt a migraine.

This report proposes that magnesium may play a complex role in attenuating migraines by acting as an acute abortive agent, as well as a prophylactic.  It was emphasized that magnesium is low cost, safe, and an easy-to-implement migraine intervention.  Authors give advice regarding optimal dosing for migraine management and note that oral and intravenous formats can be utilized.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/19271946

2008: The effects of magnesium prophylaxis in migraine without aura.

A study by Köseoglu et al. (2008) investigated the efficacy of magnesium for the management of migraine without aura (also referred to as “common migraine”).  Previous research failed to investigate the efficacy of magnesium as a migraine prophylactic among those suffering migraine without aura.  For this reason, researchers recruited 40 patients with common migraine (without aura) to partake in a double-blinded, randomized, placebo-controlled study.

A total of 30 patients were administered magnesium citrate (600 mg/day) orally for a 3-month term, whereas 10 patients were given a placebo.  Prophylactic efficacy of the magnesium citrate was determined based on clinical evaluation, visual evoked potential, and statistical parametric mapping of brain single photon emission computerized tomography (before vs. after treatment).  Results indicated that magnesium citrate (600 mg/day) reduced migraine attack frequency, severity, and P1 amplitude in visual evoked potential after 90 days – compared to the placebo.

Interestingly, significant changes in cortical blood flow were noted within the inferolateral frontal, inferolateral temporal, and insular areas of the brain following magnesium treatment (compared to pre-treatment).  Based on the results, researchers believe that magnesium is therapeutic for prophylaxis of migraines without aura (common migraine).  They hypothesize that magnesium may modulate blood vessel size and nervous system activity to prevent migraine attacks.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/18705538

2004: A combination of riboflavin, magnesium, and feverfew for migraine prophylaxis: a randomized trial.

A trial conducted by Maizels et al. (2004) assessed a non-pharmacological combination treatment for migraine prophylaxis.  Specifically, they sought to test the efficacy of Riboflavin (vitamin B2), Magnesium, and Feverfew (Tanacetum parthenium).  Since all three of the aforestated agents have demonstrated preliminary efficacy in the prevention of migraine attacks, it made logical sense to determine whether combining them would be more effective than each as a standalone.

Prior to the trial, it was noted that Magnesium and Feverfew data were conflicting, and Riboflavin research was limited to a single study.  Researchers organized a randomized, placebo-controlled, double-blinded study over a period of 3 months.  Of the 49 participants that completed the trial, some has received the combination treatment (400 mg Riboflavin, 300 mg Magnesium, 100 mg Feverfew), while others received a standalone Riboflavin placebo.

Efficacy of the intervention was measured by at least a 50% reduction in migraine attacks.  Results indicated that there were no significant differences between those receiving the combination treatment compared to the placebo.  That said, compared to baseline measures, it appeared as though both the combination and placebo groups exhibited significant reduction in number of migraines, days with migraines, as well as migraine index scores.

Researchers reflected upon the fact that the placebo response in this trial exceeds that of previous migraine studies.  Since Riboflavin has been shown to provide some benefit as a standalone intervention, it wasn’t a legitimate “placebo” and may have skewed results.  Although this study didn’t find significant therapeutic benefit comparing the combination to the placebo – further research is warranted with an appropriate placebo to better understand the efficacy of combined non-pharmacologic agents.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/15447697

2003: Oral magnesium oxide prophylaxis of frequent migrainous headache in children: a randomized, double-blind, placebo-controlled trial.

A study by Wang et al. (2003) tested the prophylactic efficacy of magnesium among children with migraine headaches.  The impetus for this study was based on the fact that no safe and/or well-tolerated prophylactic agents are approved for the treatment of pediatric migraines.  For participants, researchers recruited 118 pediatrics (ages 3 to 17) that had experienced weekly moderate-to-severe headaches with throbbing or pulsation – for the minimal duration of a month.

The study was randomized, double-blinded, and placebo-controlled with a parallel-group design.  A total of 58 participants were assigned to receive either oral magnesium oxide (9 mg/kg per day, divided into 3 equal doses) whereas 60 were given a matching placebo – for a total of 4 months.  To determine the efficacy of magnesium oxide as a migraine prophylactic compared to the placebo, researchers assessed number of headache days after 2-week intervals throughout the 16-week period.

Of the initial 118 participants, only 86 successfully completed the 4-month study; 42 in the magnesium oxide group and 44 in the placebo group.  It was mentioned that the magnesium and placebo groups were similar in terms of demographics, health, and headache history – minimizing likelihood of potential confounds.  Results indicated that headache frequency was significantly reduced among those receiving magnesium oxide (9 mg/kg per day, divided into 3 doses), but no significant reduction occurred among the placebo group.

Furthermore, those receiving magnesium oxide also exhibited reduced headache severity compared to the placebo controls.  Despite the clinically significant efficacy of magnesium oxide in reducing headache frequency, there was also a fairly strong response to the placebo – resulting in insignificant differences between the magnesium oxide and placebo groups.  In other words, although the group receiving the magnesium oxide had significantly fewer headache days than baseline and the placebo group did not, the reduction in headache days among those receiving the magnesium oxide was not significantly different when compared to those receiving the placebo control.

Logically, since magnesium oxide was statistically significant in reducing headache days, and the placebo was not, it is likely that magnesium oxide is a safe, effective intervention for pediatrics with migraines.  The lack of statistical efficacy in terms of headache frequency reduction compared to a placebo likely resulted from an abnormally strong placebo response.  Additionally, it is important to emphasize that evidence was able to prove statistically significant reductions in headache severity among those taking magnesium oxide compared the placebo.

Researchers noted that this study does not demonstrate the clinical efficacy of magnesium oxide for migraine prophylaxis among pediatrics.  However, it appears as though treatment with magnesium oxide was able to significantly reduce headache days (compared to pre-treatment) and attenuate migraine-related pain.  For obvious reasons, larger-scale trials to test the efficacy of magnesium oxide as a migraine prophylactic among pediatrics are warranted.  The results of this study should lead many to speculate that magnesium may be a safe, tolerable migraine prophylactic among pediatrics.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/12786918

2002: Oral magnesium load test in patients with migraine.

A study conducted by Trauninger et al. (2002) sought to determine whether individuals with migraines are deficient in magnesium.  The study was organized based on the fact that magnesium deficiencies have been hypothesized as playing a critical role in the pathogenesis of migraine attacks.  Prior to this study there were no reports documenting total body magnesium levels among individuals with migraines.

For the study, researchers recruited 20 migraine patients and compared their magnesium levels to 20 healthy volunteers.  To determine magnesium levels in all of the participants, baseline magnesium levels were measured via serum and urine testing.  Thereafter, all 40 participants received 3000 mg magnesium lactate (oral) to “load the magnesium.”

Following the loading of magnesium lactate, magnesium levels were tested again via serum and urine over a 24-hour period to determine total excretion following magnesium loading.  The results from the study were intriguing.  At baseline (prior to loading), migraine patients failed to differ from healthy volunteers in terms of serum and urinary magnesium concentrations.

It may be important to note that there was a trend of reduced magnesium within urinary excretions among migraine patients, but this trend wasn’t statistically significant (P = 0.64).  After the loading of magnesium lactate (3000 mg), concentrations were significantly greater than baseline in both the migraine and control groups.  However, the 24-hour urinary excretion measurements were significantly reduced among those with migraines compared to the healthy controls; serum concentrations remained similar.

From this study, it is apparent that migraine patients appear to excrete less magnesium after oral loading than healthy volunteers.  Researchers believe the reduced excretion is a result of increased magnesium retention among migraine sufferers.  The increased retention occurs because the body needed the additional magnesium and stored it, whereas the healthy volunteers didn’t need the extra magnesium and thus excreted the extra.  This suggests that migraine sufferers are more likely to suffer from an underlying magnesium deficiency than those without migraines.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/12005285

2001: Deficient energy metabolism is associated with low free magnesium in the brains of patients with migraine and cluster headache.

Researchers Lodi et al. (2001) aimed to determine energy metabolism among those with migraines and cluster headaches by using neuroimaging technology.  For the study, 78 patients with migraines and 13 patients with cluster headaches were recruited.  To assess metabolism within the brains of these patients, researchers used phosphorus magnetic resonance spectroscopy (MRS) – a non-invasive technique using ionizing radiation to accurately track metabolism.

They honed in on the cytosolic free magnesium concentrations and free energy released by ATP (adenosine triphosphate) hydrolysis reactions.  Data from the MRS neuroimaging revealed that all individuals with migraines and cluster headaches exhibited abnormally low cytosolic free magnesium (Mg2+) and free energy released from ATP hydrolysis – within the occipital lobe of the brain.  Findings from this research provide additional evidence to support the idea that insufficient free magnesium (Mg2+) in brain tissues is implicated in migraines and headaches.

However, the decrease in free magnesium (Mg2+) within tissues exhibiting mitochondrial dysfunction is a downstream effect of a bioenergetics deficit.  In other words, researchers believe that low brain cytosolic free magnesium may not directly cause migraines and/or headaches, rather the underlying abnormalities in bioenergetics triggers the low magnesium and migraines.  That said, this data does not discount the usefulness of magnesium supplementation as a migraine prophylactic.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/11306197

1998: Role of magnesium in the pathogenesis and treatment of migraines.

A report by Mauskop and Altura (1998) discussed how magnesium plays a role in the pathogenesis and treatment of migraines.  Researchers reflected upon numerous clinical trials and experiments documenting low magnesium as a possible cause of migraine attacks.  Though the exact role of low magnesium in migraines remains unclear, it is understood that magnesium influences the neurotransmission of serotonin, nitric oxide, and NMDA receptor activation.

It could be that its modulation of serotonin, nitric oxide, NMDA receptors – or a cumulative modulation of all three – contribute to migraine reduction.  Authors of this report highlight the fact that approximately 50% of all migraine patients have deficiencies in concentrations of ionized magnesium.  Some evidence suggests that magnesium infusions are able to quickly provide relief from acute migraine attacks among those with underlying deficiencies, essentially serving as an abortive therapy.

Multiple double-blind studies document the fact that chronic oral magnesium supplementation significantly decreases frequency of migraine headaches.  Since magnesium is considered extremely safe and inexpensive, researchers recommend that migraine sufferers test the efficacy of oral magnesium supplementation.  Those with refractory migraines were recommended to test intravenous magnesium sulfate infusions.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/9523054

1996: Intravenous magnesium sulfate rapidly alleviates headaches of various types.

In 1996, Mauskop et al. sought to determine whether intravenous administration of magnesium sulfate could treat headaches.  Prior to this study, there was mounting evidence to suggest that deficiencies in magnesium may directly cause headaches.  A total of 40 patients were recruited for the study – 16 with classic migraines (aura), 11 with chronic migraines, 9 with cluster headaches, and 4 with chronic tension-type headaches.

Participants were administered intravenous magnesium sulfate (MgSO4) at doses of 1 gram.  Researchers aimed to draw correlations between clinical responses and basal serum ionized magnesium (IMg2+) levels, as well as specific headache subtypes and serum magnesium (IMg2+).  To determine total serum magnesium, researchers used atomic absorption spectroscopy and a Kodak Ektachem DT 60 analyzer.

Results indicated that headache pain was entirely eradicated in 80% of patients within 15 minutes of magnesium sulfate (MgSO4) infusions, suggesting its practicality as an abortive antimigraine intervention. Administration of MgSO4 appeared to fully attenuate headache symptoms of sight/sound sensitivity and nausea. In 56% of the patients, worsening of headache pain or recurrent headaches did not occur within 24 hours of magnesium sulfate infusions.

There was a direct correlation between efficacy of magnesium sulfate as an intervention and IMg2+ levels, implying that greater concentrations alleviated headache symptoms.  In 32 patients (80%), instantaneous relief from headache pain was attained.  Over half of those who attained instant headache pain relief from magnesium sulfate experienced relief exceeding 24+ hours post-administration.

Treatment with magnesium sulfate (MgSO4) wasn’t associated with any adverse reactions, although a few patients reported transient “flushed” feelings.  Patients that attained the greatest relief from magnesium sulfate infusions exhibited the lowest pre-treatment levels of IMg2+, whereas non-responders exhibited significantly greater pre-treatment IMg2+ concentrations.  Interestingly, although all headache subtypes (e.g. migraine with aura, common migraine, cluster, etc.) exhibited low serum IMg2+ during headache attacks, individuals with cluster headaches appeared to have the lowest overall IMg2+, comparatively.

Researchers concluded that intravenous magnesium sulfate infusions (1 gram) can provide fast-acting headache relief among those with various types of headaches.  Benefits appear to be most prominent among those with low serum IMg2+ and non-existent among those with normative or elevated IMg2+.  Measuring IMg2+ concentrations may be a practical way to determine whether an individual is likely to derive therapeutic antimigraine benefit from magnesium sulfate infusions.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/8984087

1996: Prophylaxis of migraine with oral magnesium: results from a prospective, multi-center, placebo-controlled and double-blind randomized study.

A placebo-controlled, double-blinded, randomized study was conducted by Peikert et al. (1996) documenting whether oral magnesium was useful as a migraine prophylactic.  Researchers recruited 81 patients (aged 18 to 65 years) with migraines (diagnosed in accordance with International Headache Society standards) to participate in the study.  To determine pre-treatment migraine frequency, researchers assessed patients for a 4-week baseline period.

Thereafter, patients were administered either: magnesium (trimagnesium dicitrate) at 600 mg per day (orally) or a placebo – for a duration of 12 weeks.  Results indicated that by weeks 9 to 12, migraine attack frequency had decreased by approximately 41.6% among the individuals taking magnesium (600 mg/day) and only 15.8% in the placebo group – compared to the pre-treatment baseline.  Specifically, the total number of days with migraine attacks and abortive antimigraine medication usage had significantly decreased among the magnesium group (compared to the placebo).

In addition, the length of migraine attacks and their respective intensities had diminished among those taking magnesium, but failed to differ significantly from the placebo.  Some adverse reactions to the magnesium included diarrhea (18-19% of patients) and gastrointestinal distress (4-5% of patients).  In conclusion, daily administration of high-dose oral magnesium was effective as a migraine prophylactic.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/8792038

1996: Magnesium in the prophylaxis of migraine–a double-blind placebo-controlled study.

Researchers Pfaffenrath et al. (1996) reflect on the fact that administration of 10 mmol magnesium (b.i.d.) has been effective for migraine prophylaxis in previous placebo-controlled, double-blinded, randomized studies.  To conduct another study, researchers recruited 150 patients diagnosed with migraines.  All patients recruited for this study had experienced between 2 and 6 migraine attacks per month (with or without aura) and a migraine history of at least 2 years.

Similar to other studies, researchers assessed participants for 4-weeks for a baseline measure.  Following the initial 4-week baseline, individuals were administered magnesium or a placebo for a duration of 12 weeks.  The primary endpoint to determine efficacy of magnesium was a 50% reduction in the intensity or duration of migraine attacks following 12-weeks – compared to the baseline.

A total of 69 patients completed the trial and results were assessed – 35 of whom received magnesium and 34 of whom received the placebo.  Within each group, 10 individuals exhibited significant responses in accordance with the endpoint (50% reduction in intensity or duration of attacks).  There appeared to be zero benefit associated with administering magnesium for migraine prophylaxis.

Additionally, a significant number of adverse reactions such as diarrhea and stool softening were reported among 45.7% of those taking the magnesium – contrasting with just 23.5% of those taking the placebo.  These results suggest that magnesium is an ineffective intervention for those with chronic migraines and that treatment may result in adverse events.  This study is evidence to suggest that magnesium lacks efficacy as a migraine prophylactic.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/8902254

1996: Magnesium taurate and fish oil for prevention of migraine.

A report by McCarty (1996) suggests that magnesium taurate and fish oil may effectively prevent migraine attacks.  McCarty hypothesizes that increasing extracellular magnesium and tissue concentrations of taurine – may decrease hyperexcitability of neurons, counteract vasospasm, increase tolerance to focal hypoxia, and stabilize platelets – all of which may reduce likelihood of a migraine attack.  Since magnesium taurate delivers both magnesium and taurine – it may be a superior form of magnesium to administer migraine sufferers as a prophylactic.

Fish oil was also discussed in prophylaxis of migraine due to the fact that it stabilizes platelets and may prevent rapid constriction of blood vessels that precede cortical spreading depression.  Perhaps a combination of magnesium taurate and fish oil would provide more benefit than either as a standalone intervention as a migraine prophylactic.  Although this is a speculative report, it provides reason to believe that magnesium taurate and fish oil are safe and possibly effective antimigraine agents.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/8961243

1991: Magnesium prophylaxis of menstrual migraine: effects on intracellular magnesium.

A study published in 1991 conducted by Facchinetti et al. assessed the efficacy of magnesium in the prophylaxis of menstrual migraines.  A total of 20 patients diagnosed with menstrual-related migraines participated in a double-blinded, placebo-controlled study.  They were given either: magnesium pyrrolidone carboxylic acid (360 mg/day) or a placebo – starting on the 15th day of a menstrual cycle and continued until the next cycle (for 2 months).

After the 2 months of patients receiving either magnesium or a placebo, magnesium was administered to all patients for an additional 2 months.  Results indicated that during the second month of treatment, Pain Total Index (PTI) scores had significantly diminished among those receiving magnesium and the placebo.  Total number of headache days was only reduced among those receiving the magnesium (360 mg/day).

Furthermore, magnesium supplementation ameliorated premenstrual symptoms as evidenced by decreases in Menstrual Distress Questionnaire (MDQ) scores.  By the 4th month of treatment (when all participants had been receiving magnesium for at least 2 months), reductions in PTI scores and MDQ scores were significant.  Measures indicated that intracellular concentrations of Mg++ were reduced among those with menstrual migraines prior to treatment with magnesium, but during treatment they had increased.

Researchers concluded that there is an inverse relationship between PTI scores and Mg++ levels.  Evidence from this study suggests that magnesium supplementation is an effective prophylactic among women with menstrual migraines – and that a magnesium deficiency may be the underlying cause.  Finally, it is important to note that magnesium supplementation appears to reduce unwanted symptoms of menstrual distress.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/1860787

1989: Low brain magnesium in migraine.

Among the first studies to make a connection between low magnesium and migraines was conducted by Ramadan et al. (1989) and published in “Headache.”  Researchers recruited migraine patients and measured brain magnesium levels, comparing the levels to those of non-migraine patients.  They used “in vivo” nuclear magnetic resonance spectroscopy to determine pMg and pH.

The pMg and pH were assessed based on chemical shifts between signals of ATP, PCr, and Pi.  Results indicated that magnesium levels were abnormally low during migraine attacks without any alterations in pH.  Researchers believed that abnormally low brain magnesium plays a critical role in the mechanisms of migraine attacks.

Although authors didn’t recommend that migraine sufferers supplement with magnesium, most would speculate that supplementation could help reduce migraines.  That said, it is difficult to determine whether low magnesium is a direct cause of migraines or a byproduct of another, more direct cause.  Nonetheless, it is clear that migraine sufferers exhibit reductions in neural magnesium during an attack.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/2584000

Limitations associated with research of magnesium for migraines

There are several limitations associated with research of magnesium for migraines.  Much of the literature investigating the efficacy of magnesium as an antimigraine therapy incorporated small sample sizes.  In addition to small sample sizes, the research tested different types of magnesium, modalities of administration, as well as doses.  Perhaps most problematic is the fact that magnesium supplementation was tested on migraine patients without deficiencies – a population for whom increasing magnesium intake is unlikely to provide therapeutic benefit.

  • Dosing: The most effective dosage of magnesium for migraine prevention and/or attenuation remains unknown. It may be that optimal magnesium dosing for one person is entirely different than that for another.  For example, someone with a slight magnesium deficiency may only require a low supplemental dose of magnesium to prevent migraines, whereas someone with a significant deficiency may require a much higher dose to derive preventative benefit.  Additionally, it is difficult to know whether higher dosing provides greater acute abortive relief than lower dosing.
  • Causative (?): Some research has hinted at the fact that low magnesium may not be the direct cause of migraines. It may be that mitochondrial dysfunction leads to migraines and causes low magnesium.  For certain migraine sufferers, magnesium may have nothing to do with the actual migraines and may provide no antimigraine benefit when supplemented.  Further research should investigate whether magnesium is more of a direct cause or secondary biochemical consequence of a different neurophysiologic abnormality implicated in migraines.
  • Long-term outcomes: Studies have investigated the antimigraine efficacy of magnesium over a duration of 4 months (16 weeks), but none have been conducted over longer terms. It is possible that the body may adapt to supplemental magnesium and that the efficacy of exogenously administered magnesium may diminish over a longer-term (e.g. years).  Longitudinal studies may be helpful for understanding tolerability and efficacy of supratherapeutic and/or exogenous magnesium supplementation over an extended duration.
  • Measuring magnesium: It is challenging for researchers to determine which migraine patients are deficient in magnesium (and therefore most likely to benefit from its supplementation). This is because levels in the bloodstream may only account for 2% of total body magnesium stores.  A considerable amount of magnesium is stored within bones and intracellularly.  Also, blood levels of magnesium are not necessarily reflective of concentrations within the brain.  Someone may appear to have sufficient magnesium on a blood test, yet exhibit deficiencies within the brain (and vice-versa).  As researchers come up with more effective ways to measure brain magnesium, it should be easier to determine whether it is an effective intervention among those with deficits.
  • Modality of administration: In the research of magnesium for migraines, two common modalities of administration have been tested: orally and intravenously. Intravenous infusions appear to be highly effective as an acute, abortive migraine therapy.  On the other hand, regular oral administration is considered effective as a prophylactic.  Nonetheless, it may be helpful to investigate and compare efficacy of all modalities of magnesium administration among migraine patients.  Moreover, it may be beneficial to consider intranasal magnesium formats to rapidly bypass the blood-brain-barrier while simultaneously improving tolerability by reducing likelihood of gastrointestinal side effects.
  • Non-magnesium deficient migraine patients: Up to half of all migraine patients do not exhibit deficiencies in magnesium. Studies have shown that patients without deficiencies are unlikely to derive any sort of benefit from magnesium supplementation.  Since non-magnesium deficient patients were tested along with migraine patients that were magnesium deficient, it skews the data to make magnesium look less effective as an intervention.  Future testing should focus on solely recruiting patients with magnesium deficits to test its efficacy as an antimigraine intervention.
  • Sample sizes: While many studies investigating magnesium for migraines are robustly designed (placebo-controlled, double-blinded, randomized) – not all incorporate large samples. Without large samples, it is difficult to establish whether magnesium is effective for the management of migraines.  Although well-designed trials with small samples may have yielded accurate results, the fact that data is mixed regarding magnesium’s efficacy indicates that larger samples are warranted for future research.
  • Standalone vs. combination vs. adjunct: Currently we aren’t sure as to whether magnesium is most effective when administered as a standalone supplement, as part of a combination (e.g. with CoQ10, Fish Oil, and/or Riboflavin), or as an adjunct such as to a pharmaceutical medication like Amitriptyline. It may be that magnesium is equally effective as a standalone antimigraine agent when compared to its usage as part of a supplemental blend.  It may also be that the supplemental blend acts synergistically and provides greater benefit than standalone magnesium.
  • Type of magnesium: It is unclear as to whether a specific type of magnesium is safer, more tolerable, and/or more effective than another for the treatment of migraines. Types of magnesium administered in migraine studies include: magnesium citrate, magnesium lactate, magnesium oxide, magnesium pyrrolidone carboxylic acid, magnesium sulfate, magnesium taurate, trimagnesium dicitrate, etc.  It should be speculated that certain types of magnesium may be more tolerable and/or effective than others for migraine management.

Verdict: Magnesium effective for a subset of migraine patients

Based on the available scientific literature, it appears as though magnesium is highly effective as a prophylactic for a subset of migraine patients, specifically those with preexisting magnesium deficiencies.  It is estimated that up to 50% of all migraine patients exhibit magnesium deficiencies, and therefore, it could be estimated that half of all individuals with migraines may derive considerable benefit from regular magnesium supplementation.  Magnesium has the potential to reduce the number of days with migraine headaches, essentially acting as a prophylactic.

It also has the potential to attenuate the severity of migraine pain during an attack.  Research suggests that administration of magnesium sulfate during an attack (via intravenous infusion) is effective in a considerable number of patients – providing nearly instantaneous migraine relief (in under 15 minutes).  As a result of these findings, some researchers have urged migraine patients to test the therapeutic efficacy of magnesium prior to pharmaceuticals.

While many migraine patients will find magnesium beneficial as a prophylactic, acute abortive therapy, or to reduce severity of symptoms – some may find it completely useless.  It is necessary to acknowledge that some migraine patients derive minimal or zero therapeutic benefit from magnesium supplementation.  The patients that are least likely to benefit from magnesium as an antimigraine intervention tend to be those without underlying deficiencies.

Nonetheless, magnesium carries an excellent safety profile and causes few side effects compared to most migraine treatments.  It may also improve health in unexpected ways (e.g. anxiety reduction, memory improvement, etc.) among patients with preexisting magnesium deficits.  The American Headache Society assigned magnesium a “Level B” rating for the treatment of migraines, indicating that it is probably effective and warrants consideration among most migraine sufferers as a prophylactic.

What dosage of magnesium is most effective for migraines?

It is difficult to pinpoint the specific dosage of magnesium that should be used for the prevention of migraines.  Some individuals may require much higher doses than others due to the fact that they are severely deficient.  Others may require significantly lower doses due to the fact that they aren’t as deficient.  Therefore, it may take some experimentation and discussion with your doctor to determine a safe, optimal dose of magnesium for migraine management.

The publication entitled “Headache: The Journal of Head and Face Pain” recommends doses of 400 mg to 500 mg per day of magnesium oxide in oral pill form for migraine prophylaxis.  When used acutely as an abortive therapy, it can be administered in pill form at a similar dose or administered intravenously as an infusion of magnesium sulfate at a dose of 1-2 grams.

Prior to taking any magnesium for the prevention or treatment of migraines, individuals should discuss its safety with a medical professional.  Dosage differences may be warranted for pediatrics and/or among those with more severe magnesium deficits.  In all cases, contraindications should be considered and ruled out among those taking other medications and/or with other health conditions (e.g. renal impairment).

  • Source: http://www.americanheadachesociety.org/assets/1/7/Magnesium_-_October_2013.pdf

What type of magnesium should you take for migraines?

There are many different types of magnesium that were tested for the management of migraines.  I personally like to take magnesium calm, a form of magnesium citrate because I like the way it tastes, believe it is efficiently absorbed, and tends to significantly reduce stress.  That said, there’s no specific magnesium that is definitively more effective or “superior” to others for migraine prophylaxis or treatment.  Below are various types of magnesium that you could consider testing if you are susceptible to migraines.

  • Magnesium Oxide (MgO): This is magnesium bound to oxygen molecules and is poorly absorbed compared to other formats. However, despite being poorly absorbed, it has the highest percentages of elemental magnesium on a per-dose basis.  If you don’t want to spend much money and hope to test magnesium for your migraines – you could try magnesium oxide; it has been shown effective for migraines.
  • Magnesium Citrate: Magnesium citrate is the type of magnesium found in the Natural Calm magnesium supplement that I personally take. Magnesium is bound with citric acid to enhance absorption.  Despite the enhanced absorption, citrate is larger than oxygen molecules, which reduces magnesium by weight.
  • Magnesium Glycinate: This is simply magnesium bound to the amino acid glycine. Glycine is a large molecule, which reduces the amount of magnesium by weight.  It is important to note that glycine can alter neurotransmission and often facilitates calmness.  Although this hasn’t been tested for migraines, anecdotal accounts report its efficacy.
  • Magnesium Taurate: One of the studies discussed above suggests that magnesium taurate may be the most effective form to take for migraines. In this preparation, magnesium is bound to the amino acid taurine which can induce relaxation and enhance heart contractions.  Molecularly, taurine is large so magnesium content by weight will be reduced.
  • Magnesium Sulfate: Intravenous infusions with magnesium sulfate has been shown to rapidly alleviate headaches and migraines of various types. This may be the most effective form of magnesium for alleviation of an already-occurring migraine attack.  Studies have shown that an infusion of 1-2 grams provides symptomatic relief within 15 minutes.
  • Magnesium Threonate: Another type of magnesium that is thought to be superior to other formats in its ability to penetrate the blood-brain-barrier (BBB) is magnesium threonate (sometimes called magnesium L-threonate). If this format delivers more magnesium to the brain, it may be more effective than other formats on a per-dose basis for the management of migraines.  Some studies document that magnesium threonate is able to ameliorate cognitive deficits associated with neurodegeneration and may be a cognitive enhancer and/or neuroprotective agent in adults.

Note: There are other forms of magnesium on the market such as magnesium chelate.  To determine whether one type of magnesium may be safer or more effective than another for management of migraines, consult a medical professional.

Have you tested magnesium for migraines?

If you’ve tested magnesium supplementation as an antimigraine intervention, feel free to share your experience in the comments section below.  Discuss the efficacy of the magnesium by stating whether it was: highly effective, somewhat effective, or completely useless – as either a prophylactic or abortive agent.  In addition, mention whether you found magnesium helpful for reducing severity of migraine pain and/or other symptoms such as nausea and sensory hypersensitivity.

To help others get a better understanding of your situation, include some additional details in your comment such as: dosage you use (e.g. 400 mg/day), type/brand of magnesium (e.g. citrate / natural vitality), type of migraines you have (e.g. with aura), and cumulative duration of treatment (e.g. 2 months).  Also note whether you’re using other medications and/or supplements along with the magnesium.  Have you noticed any unwanted side effects or adverse reactions resulting from your magnesium supplementation?

For those who find magnesium helpful in reducing migraines, have you found it therapeutically effective over a long-term (e.g. years)?  Understand that most migraine patients will derive some therapeutic benefit from its administration, but whether the benefit is clinically significant is subject to interindividual variation.  Nonetheless, if you haven’t yet tested magnesium for the treatment of migraines, you may want to consider it.

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{ 1 comment… add one }
  • D. L. June 29, 2016, 1:51 pm

    This is by far the best and most complete review I have read concerning Magnesium and Migraine. It was comprehensive and balanced. Being very familiar with this literature, I realize the huge investment in time and in-depth reading that this information represents and thank you for your significant efforts. I will be sharing it with others.

    I have been recommending trials of Magnesium for migraines for many years, and find all the above to be true. For some patients it is the answer to prayer, and others it is less effective, but it is almost always worth a trial. Thank you for a such an excellent review of so many aspects of this treatment option.

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