Why all migraine patients should be treated with magnesium

Abstract

Magnesium, the second most abundant intracellular cation, is essential in many intracellular processes and appears to play an important role in migraine pathogenesis. Routine blood tests do not reflect true body magnesium stores since <2 % is in the measurable, extracellular space, 67 % is in the bone and 31 % is located intracellularly. Lack of magnesium may promote cortical spreading depression, hyperaggregation of platelets, affect serotonin receptor function, and influence synthesis and release of a variety of neurotransmitters. Migraine sufferers may develop magnesium deficiency due to genetic inability to absorb magnesium, inherited renal magnesium wasting, excretion of excessive amounts of magnesium due to stress, low nutritional intake, and several other reasons. There is strong evidence that magnesium deficiency is much more prevalent in migraine sufferers than in healthy controls. Double-blind, placebo-controlled trials have produced mixed results, most likely because both magnesium deficient and non-deficient patients were included in these trials. This is akin to giving cyanocobalamine in a blinded fashion to a group of people with peripheral neuropathy without regard to their cyanocobalamine levels. Both oral and intravenous magnesium are widely available, extremely safe, very inexpensive and for patients who are magnesium deficient can be highly effective. Considering these features of magnesium, the fact that magnesium deficiency may be present in up to half of migraine patients, and that routine blood tests are not indicative of magnesium status, empiric treatment with at least oral magnesium is warranted in all migraine sufferers.

This is a preview of subscription content, log in to check access.

References

  1. Abraham GE, Lubran MM (1981) Serum and red cell magnesium levels in patients with premenstrual tension. Am J Clin Nutr 34:2364–2366

    PubMed  CAS  Google Scholar 

  2. Altura BT, Altura BM (1982) The role of magnesium in etiology of strokes and cerebrovasospasm. Magnesium 1:277–291

    Google Scholar 

  3. Altura BT, Altura BM (1987) Endothelium-dependent relaxation in coronary arteries requires magnesium ions. Br J Pharmacol 91:449–451

    PubMed  CAS  Google Scholar 

  4. Altura BT, Altura BM (1989) Withdrawal of magnesium causes vasospasm while elevated magnesium produced relaxation of tone in cerebral arteries. Neurosci Lett 20:323–327

    Article  Google Scholar 

  5. Altura BT, Shirley T, Young CC, Dell’Ofrano K, Handwerker SM, Altura BM (1992) A new method for the rapid determination of ionized Mg2+ in whole blood, serum and plasma. Meth Find Exp Clin Pharmacol 14(4):297–304

    CAS  Google Scholar 

  6. Baudouin-Legros M, Dard B, Guichency P (1986) Hyperreactivity of platelets from spontaneously hypertensive rats. Role of external magnesium. Hypertension 8:694–699

    PubMed  CAS  Google Scholar 

  7. 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 22:345–353

    PubMed  Article  CAS  Google Scholar 

  8. Cete Y, Dora B, Ertan C, Ozdemir C, Oktay C (2005) A randomized prospective placebo-controlled study of intravenous magnesium sulphate vs. metoclopramide in the management of acute migraine attacks in the emergency department. Cephalalgia 25:199–204

    PubMed  Article  CAS  Google Scholar 

  9. Coan EJ, Collingridge GL (1985) Magnesium ions block an N-methyl d-aspartate receptor-mediated component of synaptic transmission in rat hippocampus. Neurosci Lett 53:21–26

    PubMed  Article  CAS  Google Scholar 

  10. Corbo J, Esses D, Bijur PE, Iannaccone R, Gallagher EJ (2001) Randomized clinical trial of intravenous magnesium sulfate as an adjunctive medication for emergency department treatment of migraine headache. Ann Emerg Med 38:621–627

    PubMed  Article  CAS  Google Scholar 

  11. Durlach J (1976) Neurological manifestations of magnesium imbalance. In: Vinken PJ, Bruyn GW (eds) Handbook of clinical neurology, vol 28. North-Holland Publishing Co, Amsterdam

    Google Scholar 

  12. Fabricius M, Fuhr S, Bhatia R et al (2006) Cortical spreading depression and peri-infarct depolarization in acutely injured human cerebral cortex. Brain 129:778–790

    PubMed  Article  Google Scholar 

  13. Facchinetti F, Sances G, Borella P, Genazzani AR, Nappi G (1991) Magnesium prophylaxis of menstrual migraine: effects on intracellular magnesium. Headache 31:298–301

    PubMed  Article  CAS  Google Scholar 

  14. Foster AC, Fagg GE (1987) Neurobiology. Taking apart NMDA receptors. Nature 329:395–396

    PubMed  Article  CAS  Google Scholar 

  15. Goadsby PJ (2006) Migraine: emerging treatment options for preventive and acute attack therapy. Expert Opin Emerg Drugs 11:419–427

    PubMed  Article  CAS  Google Scholar 

  16. Goldstein S, Zsoter TT (1978) The effect of magnesium on the response of smooth muscle to 5-hydroxytryptamine. Br J Pharmacol 62:507–514

    PubMed  CAS  Google Scholar 

  17. Hadjikhani N, Sanchez Del Rio M, Wu O et al (2001) Mechanisms of migraine aura revealed by functional MRI in human visual cortex. Proc Natl Acad Sci USA 98:4687–4692

    PubMed  Article  CAS  Google Scholar 

  18. Hoskin KL, Bulmer DCE, Goadsby PJ (1999) Fos expression in the trigeminocervical complex of the cat after stimulation of the superior sagittal sinus is reduced by l-NAME. Neurosci Lett 266:173–176

    PubMed  Article  CAS  Google Scholar 

  19. Huang QF, Gebrewold A, Zhang A et al (1994) Role of excitatory amino acids in regulation of rat pial microvasculature. Am J Physiol 266:R158–R163

    PubMed  CAS  Google Scholar 

  20. Innerarity S (2000) Hypomagnesemia in acute and chronic illness. Crit Care Nurs Q 23:1–19

    PubMed  CAS  Google Scholar 

  21. Jain AC, Sethi NC, Balbar PK (1985) A clinical electroencephalographic and trace element study with special reference to zinc, copper and magnesium in serum and cerebrospinal fluid (CSF) in cases of migraine. J Neurol Suppl 232:161

    Google Scholar 

  22. Mauskop A, Altura BT, Cracco RQ, Altura BM (1995a) Intravenous magnesium sulfate relieves cluster headaches in patients with low serum ionized magnesium levels. Headache 35:597–600

    PubMed  Article  CAS  Google Scholar 

  23. Mauskop A, Altura BT, Cracco RQ, Altura BM (1995b) Intravenous magnesium sulfate relieves migraine attacks in patients with low serum ionized magnesium levels: a pilot study. Clin Sci 89:633–636

    PubMed  CAS  Google Scholar 

  24. Mauskop A, Altura BT, Cracco RQ, Altura BM (1996) Intravenous magnesium sulfate rapidly alleviates headaches of various types. Headache 36:154–160

    PubMed  Article  CAS  Google Scholar 

  25. Mauskop A, Altura BT, Altura BM (2002) Serum ionized magnesium levels and serum ionized calcium/ionized magnesium ratios in women with menstrual migraine. Headache 42:242–248

    PubMed  Article  Google Scholar 

  26. Mayevsky A, Doiron A, Manor T et al (2006) Cortical spreading depression recorded from the human brain using a multiparametric monitoring system. Brain Res 740:268–274

    Article  Google Scholar 

  27. Mazzotta G, Srachielli P, Alberti A, Gallai V (1999) Intracellular Mg2+ concentration and electomyographical ischemic test in juvenile headache. Cephalalgia 19:802–809

    PubMed  Article  CAS  Google Scholar 

  28. Meller ST, Gebhart GF (1993) Nitric oxide (NO) and nociceptive processing in the spinal cord. Pain 52:127–136

    PubMed  Article  CAS  Google Scholar 

  29. Myrdal U, Leppert J, Edvinsson L et al (1994) Magnesium sulphate infusion decreases circulating calcitonin gene-related peptide (CGRP) in women with primary Raynaud’s phenomenon. Clin Physiol 14:539–546

    PubMed  Article  CAS  Google Scholar 

  30. Olesen J, Thomsen LL, Eversen H (1994) Nitric oxide is a key molecule in migraine and other vascular headaches. Trends Pharmacol Sci 15:149–153

    PubMed  Article  CAS  Google Scholar 

  31. Peikert A, Wilimzig C, Kohne-Volland R (1996) Prophylaxis of migraine with oral magnesium: results from a prospective, multi-center, placebo-controlled and double-blind randomized study. Cephalalgia 16:257–263

    PubMed  Article  CAS  Google Scholar 

  32. Peters JA, Hales TG, Lambert JJ (1988) Divalent cations modulate 5-HT3 receptor-induced currents in N1E-115 neuroblastoma cells. Eur J Pharmacol 151:491–495

    PubMed  Article  CAS  Google Scholar 

  33. Pfaffenrath V, Wessely P, Meyer C et al (1996) Magnesium in the prophylaxis of migraine-A double-blind, placebo-controlled study. Cephalalgia 16:436–440

    PubMed  Article  CAS  Google Scholar 

  34. Ramadan NM, Halvorson H, Vande-Linde A et al (1989) Low brain magnesium in migraine. Headache 29:590–593

    PubMed  Article  CAS  Google Scholar 

  35. Rozen TD (2003) Aborting a prolonged migrainous aura with intravenous prochlorperazine and magnesium sulfate. Headache 43:901–903

    PubMed  Article  Google Scholar 

  36. Schimatschek HF, Rempis R (2001) Prevalence of hypomagnesemia in an unselected German population of 16,000 individuals. Magnes Res 14:283–290

    PubMed  CAS  Google Scholar 

  37. Soriani S, Arnaldi C, De Carlo L et al (1995) Serum and red blood cell magnesium levels in juvenile migraine patients. Headache 35:14–16

    PubMed  Article  CAS  Google Scholar 

  38. Strong AJ (2003) Detecting and characterizing spreading depression in the injured human brain. J Cereb Blood Flow Metab 23:748

    Google Scholar 

  39. Strong AJ, Fabricius M, Boutelle MG et al (2002) Spreading and synchronous depressions of cortical activity in acutely injured human brain. Stroke 33:2738–2743

    PubMed  Article  Google Scholar 

  40. Touitou Y, Godaud JP, Ferment O et al (1987) Prevalence of magnesium and potassium deficiencies in the elderly. Clin Chem 33:518–523

    PubMed  CAS  Google Scholar 

  41. Trauninger A, Pfund Z, Koszegi T, Czopf J (2002) Oral magnesium load test in patients with migraine. Headache 42:114–119

    PubMed  Article  Google Scholar 

  42. Wang F, Van Den Eeden SK, Ackerson LM et al (2003) Oral magnesium oxide prophylaxis of frequent migraine headache in children: a randomized, double-blind, placebo-controlled trial. Headache 43:601–610

    PubMed  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Alexander Mauskop.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Mauskop, A., Varughese, J. Why all migraine patients should be treated with magnesium. J Neural Transm 119, 575–579 (2012). https://doi.org/10.1007/s00702-012-0790-2

Download citation

Keywords

  • Migraine
  • Aura
  • Deficiency
  • Intravenous
  • Magnesium