Magnesium for Migraine Prevention

The effects of magnesium on migraine are impressive, especially when compared to the medications commonly prescribed by physicians. An analysis of five clinical trials determined magnesium reduced the number of migraine attacks between 22 to 43%, while preventive pharmaceutical treatments listed as effective by the American Headache Society offer an approximate 30 to 60% reduction in migraine attack frequency. There is no perfect treatment that helps everyone who experiences migraines, but magnesium is a nourishing mineral with rare side effects and ample evidence that it could support a reduction in migraines, especially for those with inadequate magnesium levels.¹

In humans, magnesium is the second most abundant positively charged mineral inside cells and the fourth most abundant in the body.² Biochemically, magnesium in the body is primarily deposited into two major compartments: approximately 60% of magnesium is in bones, 40% is in cells, and <1% of magnesium is present in the blood.^2,3 In adults, the requirement for magnesium intake is 300–400 mg/day on average, and the exact amount depends on gender, age, body habitus, physiologic need, and individual variations in both absorption in the gut and excretion.

Magnesium is primarily excreted in the urine, but magnesium loss can be exacerbated by excessive sweating since magnesium is also excreted in sweat. So, those who work outside in the heat, engage in vigorous exercise or do other activities that cause sweating might need extra magnesium.² There is also evidence of a genetic predisposition that could contribute to the presence of both migraines and suboptimal magnesium status. Therefore, genetics could increase the daily need for magnesium.¹

Magnesium is required for more than 600 enzymatic reactions that regulate critical cellular processes throughout the body.⁴ Magnesium plays a role in the regulation of ion channels and transportation, muscular and neuronal excitability and activity, bone metabolism/remodeling, calcium absorption, calcitonin stimulation, parathyroid hormone secretion, osteoblast adhesion, carbohydrate metabolism, glycolysis, glucose homeostasis, insulin secretion, lymphocyte (immune cell) synthesis and proliferation, lipid metabolism, protein synthesis, and nucleic acid (DNA, RNA) synthesis.

Several studies have investigated the relationship of magnesium to various disease states, and almost all demonstrated significant variation in the magnesium concentration between the patients and the healthy participants. Conditions that could be related to altered magnesium status include ischemic heart disease, hypertension, heart failure, metabolic syndrome, type II diabetes, insulin resistance, PCOS, arthritis, anxiety, epilepsy, multiple sclerosis, obsessive-compulsive disorder, Alzheimer’s, depression, chronic kidney disease, prostate cancer, and others.^2,5 While magnesium is one of the most important minerals, deficiency is quite common.

Magnesium deficiency occurs due to insufficient consumption of magnesium, inadequate absorption of magnesium, and/or increased magnesium excretion from the body. According to epidemiological data, over half of the US population does not consume sufficient dietary magnesium. Even those who choose a balanced diet full of whole, unprocessed foods might not consume enough magnesium because modern soil is often depleted of magnesium and other minerals. Even though magnesium deficiency is common, it is rarely diagnosed because the blood magnesium level often appears normal even when a deficiency is present. Magnesium deficiency is also associated with nonspecific symptoms, so it is easy to overlook a chronic magnesium deficiency as an underlying cause of clinical problems. Research confirms magnesium deficiency can induce a wide range of clinical complications, including painful muscle spasms, fibromyalgia, arrhythmia, osteoporosis, and migraines.⁶

Magnesium was first used as a treatment for health concerns a very long time ago, most likely in the 17th century. In the 17th century, magnesium sulfate, or Epsom salt, was prescribed to treat abdominal pain, constipation, and muscle strains.⁷ Today, oral, intravenous, and topical magnesium are widely prescribed for the prevention and treatment of pain in addition to many other symptoms and health conditions. According to a significant body of research, a low magnesium level appears to play a role in migraine pathogenesis, so improving magnesium status could reduce the frequency of migraines.⁵

Migraine is one of the most common recurrent types of headache and, according to the findings of the last Global Burden Disease study, migraine continues to be the second most common cause of disability in the world. Moreover, migraine is the #1 most common cause of disability among young women globally.^8,9 Episodic or intermittent migraine affects approximately 18% of women and 6% of men, while chronic migraine affects roughly 2% of the global population.⁹ Migraine symptoms include severe pain in the head, nausea, vomiting, extreme sensitivity to light, and extreme sensitivity to sound. A migraine can also be accompanied by a warning symptom known as an aura, which can present as visual flashes of light, blind spots, a tingling sensation in the face, and trouble speaking.⁶ Although the underlying causes and pathophysiology of migraine remain to be fully elucidated, research shows a low magnesium level could contribute to the onset of migraine by affecting neurotransmitter secretion, synaptic transmission, vasoconstriction, calcium homeostasis, ATP production, NMDA receptors, the release of inflammatory mediators CGRP and substance P, nitric oxide production, and platelet aggregation.^5-13

According to the last National Health and Nutrition Examination Survey that tracked both magnesium intake and migraines, only one out of every five individuals with migraine consumed adequate magnesium, so approximately 80% do not consume adequate dietary magnesium.¹¹ In addition to low total and ionized serum and red blood cell magnesium levels, those with migraines also tend to have low magnesium levels in saliva and cerebrospinal fluid (CSF).^8,12 Research also demonstrates a low serum concentration of magnesium is an independent risk factor for migraine attacks, and there is considerable evidence that magnesium supplementation is useful for the management and prevention of migraine headaches.^6,12

A meta-analysis of randomized controlled trials where migraine patients received intravenous magnesium (948 participants) or oral magnesium (789 participants) confirmed magnesium treatment resulted in reduced frequency and intensity of migraines.^6,13 The effects of magnesium on migraine are even more impressive when compared to other medications. A recent randomized, controlled, double-blind, crossover study by Karimi et al. concluded that treatment with magnesium is as effective for migraine prevention as the medication valproate sodium without significant adverse effects.¹⁴ Furthermore, an analysis that included five clinical trials determined magnesium reduced the number of migraine attacks between 22 to 43%, while the preventive pharmaceutical treatments listed as effective by the American Headache Society offer an approximate 30-60% reduction in migraine attack frequency.¹

Many types of medications are prescribed for migraine headaches, including β-blockers, anticonvulsants, calcium channel blockers, serotonin antagonists, tricyclic antidepressants, triptans, neuroleptics, and monoamine oxidase inhibitors. These medications are not always 100% effective, and many are associated with side effects.^8,14 Since the administration of magnesium shows comparatively few side effects, preventive treatment with trimagnesium dicitrate or other forms of bioavailable magnesium seems to be a safe and cost-efficient approach for most.^1,3,8 And, the American Headache Society, the American Academy of Neurology, the American Migraine Foundation, the Canadian Headache Society, the Swiss Headache Society, the Italian Headache Society, and other professional organizations all include magnesium as a treatment option for migraine.^1,4,13-16

As a frequent cause of disability, a migraine is much more than a headache, and there is no perfect treatment that helps everyone who experiences migraines. Magnesium is a nourishing mineral with rare side effects and abundant evidence that it could be helpful via many mechanisms to reduce the intensity and frequency of migraines, especially for those with inadequate magnesium levels.

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References:

1. von Luckner A, Riederer F. Magnesium in Migraine Prophylaxis-Is There an Evidence-Based Rationale? A Systematic Review. Headache 2018;58(2):199-209. doi:10.1111/head.13217

2. Glasdam SM, Glasdam S, Peters GH. The Importance of Magnesium in the Human Body: A Systematic Literature Review. Adv Clin Chem. 2016;73:169-93. doi:10.1016/bs.acc.2015.10.002

3. Ismail AAA, Ismail Y, Ismail AA. Chronic magnesium deficiency and human disease; time for reappraisal? QJM 2018;111(11):759-763. doi:10.1093/qjmed/hcx186

4. Domitrz I, Cegielska J. Magnesium as an Important Factor in the Pathogenesis and Treatment of Migraine-From Theory to Practice. Nutrients. 2022;14(5):1089. doi:10.3390/nu14051089

5. Mauskop A, Varughese J. Why all migraine patients should be treated with magnesium. J Neural Transm (Vienna). 2012;119(5):575-9. doi:10.1007/s00702-012-0790-2

6. Razzaque MS. Magnesium: Are We Consuming Enough?. Nutrients. 2018;10(12):1863. doi:10.3390/nu10121863

7. Shin HJ, Na HS, Do SH. Magnesium and Pain. Nutrients. 2020;12(8):2184. doi:10.3390/nu12082184

8. Dolati S, Rikhtegar R, Mehdizadeh A, et al. The Role of Magnesium in Pathophysiology and Migraine Treatment. Biol Trace Elem Res. 2020;196(2):375-383. doi:10.1007/s12011-019-01931-z

9. Aguilar-Shea AL, Membrilla Md JA, Diaz-de-Teran J. Migraine review for general practice. Aten Primaria. 2022;54(2):102208. doi:10.1016/j.aprim.2021.102208

10. Gaul C, Diener H-C, Danesch U. Migravent® Study Group. Improvement of migraine symptoms with a proprietary supplement containing riboflavin, magnesium and Q10: A randomized, placebo-controlled, double-blind, multicenter trial. Headache Pain. 2015;16:516. doi:10.1186/s10194-015-0516-6

11. Slavin M, Li H, Khatri M, et al. Dietary magnesium and migraine in adults: A cross-sectional analysis of the National Health and Nutrition Examination Survey 2001-2004. Headache. 2021;61(2):276-286. doi:10.1111/head.14065

12. Lodi R, Iotti S, Cortelli P, et al. Deficient energy metabolism is associated with low free magnesium in the brains of patients with migraine and cluster headache. Brain Res. Bull. 2001;54(4):437–441. doi:10.1016/S0361-9230(01)00440-3

13. Chiu HY, Yeh TH, Huang YC, et al. Effects of Intravenous and Oral Magnesium on Reducing Migraine: A Meta-analysis of Randomized Controlled Trials. Pain Physician. 2016;19(1):E97-112.

14. Karimi N, Razian A, Heidari M. The efficacy of magnesium oxide and sodium valproate in prevention of migraine headache: a randomized, controlled, double-blind, crossover study. Acta Neurol Belg. 2021;121(1):167-173. doi: 10.1007/s13760-019-01101-x

15. Tepper D. Magnesium and Migraine. American Migraine Foundation. Published October 20, 2021. Accessed April 22, 2022.

16. Maier JA, Pickering G, Giacomoni E, et al. Headaches and Magnesium: Mechanisms, Bioavailability, Therapeutic Efficacy and Potential Advantage of Magnesium Pidolate. Nutrients. 2020;12(9):2660. doi:10.3390/nu12092660