Magnesium for Migraines

Magnesium has been tested for migraine in two ways: as a daily oral supplement to prevent attacks, and as an intravenous infusion of magnesium sulfate during an attack. The prevention trials are small and their results differ: a 1996 German trial of 600 mg a day found attack frequency fell by 41.6% with magnesium and by 15.8% with placebo, while another 1996 trial was stopped early after finding no benefit over placebo. Meta-analyses also disagree, from a 2016 pooling that found oral magnesium reduced the frequency and intensity of attacks to a 2019 review that concluded it is unknown whether magnesium is effective for prevention in adults. The 2012 American Academy of Neurology / American Headache Society guideline graded magnesium “probably effective” (Level B); the AAN retired that guideline on September 16, 2015 because of serious safety concerns about butterbur, which it had graded Level A. For acute attacks, two meta-analyses of intravenous magnesium reached opposite conclusions, and one placebo-controlled trial found a benefit in migraine with aura but not in migraine without aura. The proposed mechanisms include magnesium’s block of the NMDA glutamate receptor and its role in cortical spreading depression, the event thought to underlie migraine aura.


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Table of Contents

  1. The Mauskop Body of Work
  2. Proposed Mechanisms — NMDA, Cortical Spreading Depression, Platelets, Energy
  3. Oral Magnesium for Migraine Prevention: the Trials
  4. The 2012 AAN / AHS Guideline (Retired in 2015)
  5. IV Magnesium for Acute Migraine
  6. Bigal and the Aura Subgroup
  7. The Pediatric Migraine Trial
  8. Menstrual Migraine
  9. Forms and Doses Used in the Trials
  10. Magnesium Alongside Riboflavin, CoQ10, Feverfew and Butterbur
  11. Side Effects, Cautions and Drug Interactions
  12. Key Research Papers
  13. Connections
  14. Featured Videos

The Mauskop Body of Work

Alexander Mauskop, a neurologist at the New York Headache Center, has written on magnesium in migraine since the 1990s. His 2012 review with Varughese in Journal of Neural Transmission is titled “Why all migraine patients should be treated with magnesium.” In it the authors argue that routine blood tests do not reflect body magnesium stores (less than 2% of body magnesium is in the measurable extracellular space), that magnesium deficiency may be present in up to half of migraine patients, and that the mixed results of double-blind trials are most likely explained by the inclusion of both deficient and non-deficient patients. On that basis they conclude that empiric treatment with at least oral magnesium is warranted in all migraine sufferers (Mauskop 2012). That is the authors’ position; the trials and reviews below show how far the evidence supports it.

  1. Low ionized magnesium during attacks — A 1998 review by Mauskop and Altura states that the available evidence suggests up to 50% of patients have lowered levels of ionized magnesium during an acute migraine attack (Mauskop 1998).
  2. IV magnesium and ionized magnesium levels — In a 1995 pilot study, 40 consecutive patients with an acute migraine received 1 g of intravenous magnesium sulfate, without a placebo group. Pain fell by 50% or more within 15 minutes in 35 patients. Relief lasted at least 24 hours in 18 of 21 patients (86%) whose serum ionized magnesium was below 0.54 mmol/L, and in 3 of 19 patients (16%) whose level was at or above it (Mauskop 1995).

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Proposed Mechanisms — NMDA, Cortical Spreading Depression, Platelets, Energy

How magnesium might act on migraine is still a set of hypotheses. The ones most often cited are:

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Oral Magnesium for Migraine Prevention: the Trials

The placebo-controlled prevention trials are small, and their results point in different directions:

  1. Peikert, Wilimzig, Köhne-Volland (1996, Cephalalgia) — 81 patients aged 18–65 with migraine (mean 3.6 attacks a month) received 600 mg (24 mmol) of magnesium a day as trimagnesium dicitrate, or placebo, for 12 weeks after a 4-week baseline. In weeks 9–12, attack frequency had fallen from baseline by 41.6% with magnesium and by 15.8% with placebo (p < 0.05). Days with migraine and use of acute medication per patient also fell significantly with magnesium; duration and intensity of attacks tended to decrease but the difference was not significant. Diarrhea was reported by 18.6% and gastric irritation by 4.7% of the magnesium group (Peikert 1996).
  2. Pfaffenrath et al. (1996, Cephalalgia) — A multicentre trial of 10 mmol of magnesium twice daily for 12 weeks in migraine without aura. The primary end-point was a reduction of at least 50% in the intensity or duration of attacks. The trial was planned for 150 patients, but the interim analysis of 69 patients found 10 responders in each group (28.6% with magnesium, 29.4% with placebo), and the trial was stopped. There was no benefit over placebo in migraine days or attacks. Mild adverse events, mainly soft stool and diarrhea, were reported by 45.7% of the magnesium group and 23.5% of the placebo group (Pfaffenrath 1996).
  3. Taubert (1994, Fortschritte der Medizin) — A double-blind, crossover, multicentre pilot study in 43 migraine patients given 600 mg of magnesium a day as trimagnesium dicitrate (article in German, English abstract). The abstract reports a significant reduction in the incidence of attacks, and states that the effect did not appear to be as large as that of the prescription preventives approved at the time (Taubert 1994).
  4. Köseoglu et al. (2008, Magnesium Research) — 600 mg a day of magnesium citrate for 3 months in migraine without aura; 30 patients on magnesium were compared with 10 on placebo. Compared with placebo, the post/pretreatment ratios of attack frequency (p = 0.005), attack severity (p < 0.001) and a visual evoked potential amplitude were lower with magnesium. Brain SPECT scans showed increased cortical blood flow in several regions after magnesium but not after placebo (Köseoglu 2008).

What the meta-analyses found

Two placebo-controlled trials of oral magnesium for migraine prevention, both published in 1996, drawn side by side. In the Peikert trial, 81 patients, 600 mg a day, attack frequency in weeks 9 to 12 fell by 41.6 percent with magnesium and by 15.8 percent with placebo, a significant difference. In the Pfaffenrath trial, an interim analysis of 69 patients, 28.6 percent responded on magnesium and 29.4 percent on placebo, and the trial was stopped. A side panel notes that the two trials used different measures, and that meta-analyses have reached conclusions ranging from benefit to unknown. TWO 1996 PREVENTION TRIALS, TWO DIFFERENT RESULTS oral magnesium vs placebo, 12 weeks each · the bars are percentages, but of different measures PEIKERT 1996 · 81 PATIENTS · 600 MG A DAY fall in attack frequency from baseline, weeks 9–12 magnesium 41.6% placebo 15.8% difference significant (p < 0.05) PFAFFENRATH 1996 · INTERIM ANALYSIS OF 69 PATIENTS responders: attack intensity or duration down by at least 50% magnesium 28.6% placebo 29.4% no benefit over placebo — the trial was stopped same year, same 12-week length one trial found fewer attacks, the other found no difference not the same yardstick Peikert counted attacks; Pfaffenrath counted responders the pooled reviews split too Chiu 2016: fewer, milder attacks Okoli 2019: effect unknown in adults Veronese 2020: strong evidence (GRADE) small trials, mixed results: the trials and the pooled reviews do not agree on prevention

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The 2012 AAN / AHS Guideline (Retired in 2015)

The 2012 evidence-based guideline of the American Academy of Neurology and the American Headache Society on NSAIDs and complementary treatments for episodic migraine prevention in adults (Holland et al., Neurology) reviewed studies published from June 1999 to May 2009 and graded:

The guideline has been retired. According to the retirement notice now printed with it, the AAN Board of Directors retired the guideline on September 16, 2015, “due to serious safety concerns with a preventative treatment, butterbur, recommended by this guideline.” The notice states that the recommendations and conclusions of retired guidelines are considered no longer valid and no longer supported by the AAN, and remain available for reference only. The Level B grade for magnesium is therefore a historical grading, not a current AAN position.

A companion 2012 AAN/AHS guideline on prescription drugs (Silberstein et al.) graded divalproex sodium, sodium valproate, topiramate, metoprolol, propranolol and timolol as effective for migraine prevention (Level A), and frovatriptan as effective for prevention of menstrual migraine (Level A) (Silberstein 2012).

Other guidance:

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IV Magnesium for Acute Migraine

Intravenous magnesium sulfate has been tested as a treatment during a migraine attack, most often at 1 g. The trials and their pooled analyses disagree:

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Bigal and the Aura Subgroup

The Bigal trial is the one most often cited for the idea that magnesium works differently in migraine with aura, the subtype in which cortical spreading depression is thought to produce the aura.

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The Pediatric Migraine Trial

One randomized, placebo-controlled trial of oral magnesium in children is among the papers cited here.

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Menstrual Migraine

Menstrual migraine is migraine whose attacks occur around the start of menstruation. One small trial has tested magnesium for it.

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Forms and Doses Used in the Trials

The trials described on this page used these forms and doses. They are reported here as study designs, not as instructions.

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Magnesium Alongside Riboflavin, CoQ10, Feverfew and Butterbur

Magnesium, riboflavin and CoQ10 are often discussed together as “mitochondrial” migraine supplements, and feverfew and butterbur are the two herbs the 2012 guideline graded. Each has been tested mostly on its own.

See Magnesium, Riboflavin, and Supplements for Migraine for more on these supplements together.

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Side Effects, Cautions and Drug Interactions

Sudden severe headache, headache with weakness, persistent visual loss, slurred speech or confusion, headache with fever and a stiff neck, and new headaches after age 50 are recognized warning signs that are evaluated medically rather than treated as routine migraine. Decisions about supplements and migraine treatment belong with a clinician.

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Key Research Papers

  1. Mauskop A, Varughese J (2012). Why all migraine patients should be treated with magnesium. Journal of Neural Transmission 119(5):575-579. — PubMed PMID: 22426836
  2. Peikert A, Wilimzig C, Köhne-Volland R (1996). Prophylaxis of migraine with oral magnesium: results from a prospective, multi-center, placebo-controlled and double-blind randomized study. Cephalalgia 16(4):257-263. — PubMed PMID: 8792038
  3. Pfaffenrath V, Wessely P, Meyer C, et al. (1996). Magnesium in the prophylaxis of migraine — a double-blind placebo-controlled study. Cephalalgia 16(6):436-440. — PubMed PMID: 8902254
  4. Köseoglu E, Talaslioglu A, Gönül AS, Kula M (2008). The effects of magnesium prophylaxis in migraine without aura. Magnesium Research 21(2):101-108. — PubMed PMID: 18705538
  5. Bigal ME, Bordini CA, Tepper SJ, Speciali JG (2002). Intravenous magnesium sulphate in the acute treatment of migraine without aura and migraine with aura. A randomized, double-blind, placebo-controlled study. Cephalalgia 22(5):345-353. — PubMed PMID: 12110110
  6. Chiu HY, Yeh TH, Huang YC, Chen PY (2016). Effects of intravenous and oral magnesium on reducing migraine: a meta-analysis of randomized controlled trials. Pain Physician 19(1):E97-E112. — PubMed PMID: 26752497
  7. Wang F, Van Den Eeden SK, Ackerson LM, Salk SE, Reince RH, Elin RJ (2003). Oral magnesium oxide prophylaxis of frequent migrainous headache in children: a randomized, double-blind, placebo-controlled trial. Headache 43(6):601-610. — PubMed PMID: 12786918
  8. Facchinetti F, Sances G, Borella P, Genazzani AR, Nappi G (1991). Magnesium prophylaxis of menstrual migraine: effects on intracellular magnesium. Headache 31(5):298-301. — PubMed PMID: 1860787
  9. Holland S, Silberstein SD, Freitag F, Dodick DW, Argoff C, Ashman E (American Academy of Neurology / American Headache Society, 2012). Evidence-based guideline update: NSAIDs and other complementary treatments for episodic migraine prevention in adults. Neurology 78(17):1346-1353. Retired by the AAN on September 16, 2015 (retirement notice printed with the PMC copy, PMC3335449). — PubMed PMID: 22529203
  10. Pringsheim T, Davenport W, Mackie G, et al. (2012). Canadian Headache Society guideline for migraine prophylaxis. Canadian Journal of Neurological Sciences 39(2 Suppl 2):S1-S59. — PubMed PMID: 22683887
  11. Welch KM, Ramadan NM (1995). Mitochondria, magnesium and migraine. Journal of the Neurological Sciences 134(1-2):9-14. — PubMed PMID: 8747836
  12. Lodi R, Iotti S, Cortelli P, et al. (2001). Deficient energy metabolism is associated with low free magnesium in the brains of patients with migraine and cluster headache. Brain Research Bulletin 54(4):437-441. — PubMed PMID: 11306197
  13. Demirkaya S, Vural O, Dora B, Topçuoğlu MA (2001). Efficacy of intravenous magnesium sulfate in the treatment of acute migraine attacks. Headache 41(2):171-177. — PubMed PMID: 11251702
  14. Ailani J, Burch RC, Robbins MS; Board of Directors of the American Headache Society (2021). The American Headache Society Consensus Statement: Update on integrating new migraine treatments into clinical practice. Headache 61(7):1021-1039. — PubMed PMID: 34160823
  15. Mauskop A, Altura BT, Cracco RQ, Altura BM (1995). Intravenous magnesium sulphate relieves migraine attacks in patients with low serum ionized magnesium levels: a pilot study. Clinical Science 89(6):633-636. — PubMed PMID: 8549082
  16. Mauskop A, Altura BM (1998). Role of magnesium in the pathogenesis and treatment of migraines. Clinical Neuroscience 5(1):24-27. — PubMed PMID: 9523054
  17. Taubert K (1994). Magnesium in migraine. Results of a multicenter pilot study (article in German, English abstract). Fortschritte der Medizin 112(24):328-330. — PubMed PMID: 7959501
  18. Okoli GN, Rabbani R, Kashani HH, et al. (2019). Vitamins and minerals for migraine prophylaxis: a systematic review and meta-analysis. Canadian Journal of Neurological Sciences 46(2):224-233. — PubMed PMID: 30764890
  19. Veronese N, Demurtas J, Pesolillo G, et al. (2020; published online 2019). Magnesium and health outcomes: an umbrella review of systematic reviews and meta-analyses of observational and intervention studies. European Journal of Nutrition 59(1):263-272. — PubMed PMID: 30684032
  20. Choi H, Parmar N (2014). The use of intravenous magnesium sulphate for acute migraine: meta-analysis of randomized controlled trials. European Journal of Emergency Medicine 21(1):2-9. — PubMed PMID: 23921817
  21. Silberstein SD, Holland S, Freitag F, Dodick DW, Argoff C, Ashman E (American Academy of Neurology / American Headache Society, 2012). Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults. Neurology 78(17):1337-1345. — PubMed PMID: 22529202
  22. Gaul C, Diener HC, Danesch U (2015). Improvement of migraine symptoms with a proprietary supplement containing riboflavin, magnesium and Q10: a randomized, placebo-controlled, double-blind, multicenter trial. Journal of Headache and Pain 16:516. — PubMed PMID: 25916335
  23. Nowak L, Bregestovski P, Ascher P, Herbet A, Prochiantz A (1984). Magnesium gates glutamate-activated channels in mouse central neurones. Nature 307(5950):462-465. — PubMed PMID: 6320006
  24. Charles A, Brennan K (2009). Cortical spreading depression — new insights and persistent questions. Cephalalgia 29(10):1115-1124. — PubMed PMID: 19735537
  25. Jahnen-Dechent W, Ketteler M (2012). Magnesium basics. Clinical Kidney Journal 5(Suppl 1):i3-i14. — PubMed PMID: 26069819
  26. de Baaij JH, Hoenderop JG, Bindels RJ (2015). Magnesium in man: implications for health and disease. Physiological Reviews 95(1):1-46. — PubMed PMID: 25540137
  27. Altman D, Carroli G, Duley L, et al.; Magpie Trial Collaboration Group (2002). Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. Lancet 359(9321):1877-1890. — PubMed PMID: 12057549

PubMed Topic Searches

  1. PubMed: Magnesium migraine prophylaxis RCTs
  2. PubMed: IV magnesium acute migraine
  3. PubMed: CSD, NMDA, and magnesium
  4. PubMed: Magnesium and menstrual migraine
  5. PubMed: Magnesium and pediatric migraine

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Connections

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