For MIGRAINES, years of research studies show that ongoing magnesium supplementation can reduce the frequency and intensity of migraines. Magnesium deficiency may cause nerve cells in the brain to misfire. Low levels of magnesium, an important mineral involved in nerve cell function, exacerbate migraine and tension headaches, and magnesium drops right before or during a migraine headache. Migraine sufferers have lower magnesium within cells and supplementation is an effective preventive.

How important is magnesium?

In 2012, the American Headache Society and the American Academy of Neurology reviewed the studies on medications used for migraine prevention and gave magnesium a Level B rating which means that it is probably effective and should be considered for patients requiring migraine preventive therapy.

Because of its safety profile and the lack of serious side effects, magnesium is often chosen as a preventive strategy either alone or with other preventive medications for these reasons:

• Magnesium is the second most abundant intracellular (inside cells) positively charged ion in the body. Recent evidence recognizes that magnesium is a cofactor in at least 600 crucial enzymatic reactions throughout the body.
• Magnesium is a cofactor in protein synthesis, cellular energy production and storage, reproduction, DNA and RNA synthesis, and mitochondrial membrane stabilization.
• Magnesium plays a critical role in maintaining normal nerve and muscle function, cardiac excitability (normal heart rhythm), neuromuscular conduction, muscular contraction, vasomotor tone, normal blood pressure, bone integrity, and glucose and insulin metabolism.
• Magnesium deficiency has been associated with several neurological disorders including migraine, Alzheimer’s disease, and cerebrovascular diseases. This is indicative of magnesium’s important role in central insulin signaling dysfunction, which is often associated with migraine pathogenesis.

Magnesium deficiency is very common in the U.S. population: According to World Health Organization statistics, as much as 75% of the U.S. adult population does not meet the U.S. Food and Drug Administration’s Recommended Daily Intake of 420mg.¹ Research also shows that the magnesium content of food sources is declining, although magnesium is found in foods like seeds, nuts, dark leafy greens, legumes, whole grains, and dark chocolate. Magnesium depletion may result from low dietary intake, poor absorption, or loss of magnesium due to excessive calcium intake, alcohol, diuretic drugs, oral contraceptives, or gastrointestinal, kidney, or liver disorders.

Magnesium is the second-most ubiquitous mineral within cells of the body after potassium. Its many health benefits arise from its role in activating a wide variety of enzymes, for numerous metabolic processes. Magnesium is especially concentrated in the brain, heart, liver, and kidneys, where it has a critical role in energy production.

How does magnesium help with migraines?

Taking extra magnesium improves blood vessel tone as it relaxes smooth muscle, and it has shown excellent results in studies for easing migraine pain. Magnesium may also help by improving mitral valve prolapse, which can cause more turbulent blood flow and clumping of platelets which then release mediators that cause dilation of blood vessels in the head.

Conversely, magnesium deficiency may cause nerve cells in the brain to misfire. This important mineral is involved in nerve cell function and low levels exacerbate migraine and tension headaches. Additionally, it has been shown that magnesium drops right before or during a migraine headache. Migraine sufferers have lower magnesium within cells and supplementation is an effective preventive.

The American Migraine Foundation issued this compelling statement, “The ideal medication for prevention and treatment of migraine would have no side effects, no risk, would be safe in pregnancy, as well as being highly effective while remaining inexpensive. Of course, no such medication exists, but magnesium comes closer than many interventions on all these fronts.”¹

Evidence and mechanism of action

The strongest evidence for magnesium’s effectiveness is in patients who have aura with their migraines. It is believed magnesium may prevent the wave of brain signaling, called cortical spreading depression, which produces the visual and sensory changes that are common with aura. Other mechanisms of magnesium action include improved platelet function and decreased release or blocking of pain-transmitting chemicals in the brain such as substance P and glutamate. Magnesium may also prevent the narrowing of brain blood vessels caused by the neurotransmitter serotonin.

Migraines respond to magnesium through several potential actions:

• Platelet function
  Serotonin is released from platelets during a migraine attack, and it can cause cerebral vasoconstriction, nausea, and vomiting. Magnesium decreases the ability of serotonin to bind to cerebral vascular muscle receptors and therefore decreases the likelihood of cerebral vasoconstriction, the narrowing of brain blood vessels, which is a factor in migraines. Magnesium helps regulate neurotransmitters such as serotonin and prevents vasoconstriction caused by serotonin.
• Cortical spreading depression
  Magnesium helps prevent cortical spreading depression, a wave of brain signaling that causes aura or visual and sensory changes common to migraine sufferers.
• Blood vessel tone
  Magnesium acts as a natural calcium channel blocker, helping to relax blood vessels and improve blood flow. Magnesium ions may block receptors that prevent calcium ions from moving between cells preventing calcium’s effects on neurons and cerebral vasoconstriction.
• Pain relief
  Magnesium decreases the release of pain-transmitting chemicals like glutamate and substance P, a neurotransmitter associated with pain perception.
• Anti-inflammatory
  Magnesium has anti-inflammatory properties that may help reduce the inflammation response involved in migraine attacks.
• Increasing the essential amino acid tryptophan
  Magnesium facilitates tryptophan release from neuronal storage sites. Since migraine headaches are related to abnormal serotonin function in blood vessels, L-tryptophan can help correct this abnormality by increasing serotonin synthesis.

There is evidence that migraineurs may have lower levels of brain magnesium either from decreased absorption of it in food, a genetic tendency to low brain magnesium, or from excreting it from the body to a greater degree than non-migraineurs. Studies of migraineurs have found low levels of brain and spinal fluid magnesium in between migraine attacks.

The science behind magnesium

An important double-blind placebo-controlled study was performed in which 24 women with menstrual-related migraine were given 360mg of magnesium divided into 3 daily doses taken from ovulation to the first day of menstrual flow. The treatment was well-tolerated, and significant reductions were observed in number of days of headache, total pain index, and in Menstrual Distress Questionnaire score.²

A larger double-blind, placebo-controlled, randomized study on 81 migraineurs who received 600mg of magnesium taken once daily, showed attack frequency reduction of 41.6% in the magnesium group versus only 15.8% in controls given placebo.³

Another significant double-blind, placebo-controlled, randomized research trial investigated the effects of 600mg of magnesium citrate supplementation per day in patients with migraine without aura. A combination of clinical assessments, visual-evoked potentials (VEPs), and brain single-photon emission computerized tomography were performed to assess the outcome and the neurogenic and vascular mechanisms of action. Taking magnesium was associated with a significant decrease in migraine attack frequency and severity, as well as decreased brain activity P1 amplitude on VEPs, and better cortical blood flow. The authors suggested that magnesium may interfere with both neurogenic and vascular mechanisms of migraine, making it an effective preventive and treatment.⁴

Evidence-based guidelines for the prevention and treatment of migraine were published in 2015 by the American Academy of Neurology and the Canadian Headache Society, providing valuable guidance for clinicians. These institutes agreed that based on the best available evidence, safety, adverse event profile, and expert consensus, magnesium citrate received a strong recommendation for use.⁵

A 2016 meta-analysis of 21 studies investigated the effects of intravenous or oral magnesium on acute migraine. They noted that oral magnesium significantly alleviated the frequency and intensity of migraines and recommended that it be adopted as part of a treatment approach to reduce migraines.⁶

Our patients’ experience with magnesium

In our clinic, migraine patients report major benefits, with fewer and less painful headaches and reduced auras and associated symptoms, with magnesium doses ranging from 300mg to 450mg daily. Depending on the form of magnesium used, larger doses over 500mg may cause loose stools, which are harmless but easily avoided. Incidentally, magnesium is frequently used as a treatment for constipation. We have found that magnesium citrate is an organic form that is particularly well-recognized by body tissues for superior absorption.

Recommendation: 300mg to 450mg of magnesium citrate or chelate daily, taken with or between meals, or as directed by your healthcare provider.

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