Review Outlines Relationship Between Magnesium Deficiency, Migraine

A systematic review concluded that a correlation between magnesium deficiency and headaches exists, while magnesium deficiency may be an independent risk factor for migraine. Findings were published in Nutrients.

Inadequate intake of magnesium, in addition to increased gastrointestinal or renal loss, can contribute to deficiency (hypomagnesemia). However, according to a large body of literature, “magnesium, with its relative lack of side effects, is particularly compelling for [headache] use in groups in which side effects are less well tolerated, such as children, pregnant women, and the elderly population.” Hypomagnesemia is common in postmenopausal women with osteoporosis and in women between ages 18 and 22.

The cation is the fourth most abundant in the human body and is involved with enzyme activity, oxidative phosphorylation, and DNA and protein synthesis, among other functions. Magnesium load tests analyze urine samples over 24 hours and are used to measure whole body magnesium.

Magnesium salts, either organic or inorganic, are used in clinical practice to treat deficiencies. Because different salts have varying absorption efficiency and soluble properties, variations in bioavailability exist.

Studies have demonstrated magnesium pidolate, an organic salt, can reverse deficiencies responsible for headaches and prevent pediatric tension-type headaches. “Magnesium pidolate has high bioavailability and good intracellular penetration, and it may reverse the magnesium deficiency responsible for headaches, even after a short administration period,” the authors wrote. Because only a limited number of studies have shown the benefits of magnesium pidolate in headaches, further controlled studies are warranted.

The researchers outlined several investigations exemplifying the association between reduced magnesium levels and migraine. Although studies have found infusion of magnesium sulfate as a treatment for acute headache yields mixed results, the authors noted only a proportion of patients with acute headaches may have magnesium deficiency, potentially masking the extent of the therapeutic effectiveness of magnesium infusion in the emergency setting.

Magnesium has also been shown to downregulate inflammation, as it inhibits pro-inflammatory intracellular signaling. Interestingly, lower concentrations of magnesium were found in brains of patients with Alzheimer disease and Parkinson disease, in addition to the occipital lobes of patients with migraine and cluster headaches compared with healthy controls. In individuals who are magnesium deficient, supplementation has been shown to attenuate anxiety and stress symptoms.

When it comes to the mechanisms underlying the relationship between magnesium deficiency and migraine, the researchers noted the deficiency is associated with cortical spreading depression (CSD) which is thought to be linked with aura accompanying some migraines. CSD is also associated with platelet activity, imbalanced neurotransmitter releases, and vasoconstriction.

“In CSD, substance P, a neuropeptide which acts as a neurotransmitter and neuromodulator, is released as a result of magnesium deficiency, possibly acting on sensory fibers and producing headache pain,” the authors wrote.

Investigations have also shown magnesium decreases the level of circulating calcitonin gene-related peptide, which is “involved in migraine pathogenesis through its ability to dilate intracranial blood vessels and produce nociceptive stimuli.”

Currently, several national and international guidelines recommend oral magnesium for headache patients. Among the studies testing magnesium’s efficacy for migraine, the most commonly reported adveradverse effects include diarrhea and gastric effects, but these events did not prevent patients from completing treatment.

“Overall, the use of oral magnesium salt represents a well-tolerated and inexpensive addition for the treatment of headache patients, to reduce the frequency of attacks and the costs of treatment both in terms of economic burden and adverse events,” the authors concluded.

Reference

Maier JA, Pickering G, Giacomoni E, Cazzaniga A, Pellegrino P. Headaches and magnesium: mechanisms, bioavailability, therapeutic efficacy and potential advantage of magnesium pidolate. Nutrients. 2020;12(9): 2660. doi:10.3390/nu12092660