Migraine and Magnesium

Timothy C. Hain, MD • Page last modified: July 20, 2020

Main points:

  • Magnesium supplements help prevent migraine
  • Medications for reflux, proton pump inhibitors, can reduce migraine absorption

Migraines are an immensely common human problem, affecting about 15% of the entire population (mainly women). A little known aspect of migraine is that they are more likely when magnesium blood levels are low, and some migraines can be aborted by large amounts of magnesium, usually given in the emergency room (Sun-edelstein et al, 2009).

The evidence for prophylaxis of migraine by magnesium in adults is reasonable, but the evidence for use in children as well as an abortive is weak. Still, magnesium is probably very safe, and for this reason it is often recommended for children.

How magnesium is regulated:

Magnesium in the blood reflects a balance between absorption in the gut and elimination through the kidney. Magnesium absorption is reduced by some stomach medications for reflux, called proton pump inhibitors. Some of them are over the counter -- e.g. prilosec. This means that it is especially important to take magnesium supplements for migraine prevention, if you take a PPI. Magnesium is regulated through the kidney, where it is reabsorbed. Incomplete reabsorption causes magnesium wasting (Viering et al, 2017).

There are about a dozen genes that result in hypmagnesiumia - but these are extremely rare in clinical medicine, and finding them does not contribute to therapy (Viering et al, 2017).

Evidence for magnesium supplements as prophylaxis:

  • Von Luekner et al (2018) suggested in a systemic review that there is grade C (possible) evidence that 600 mg of magnesium dicitrate/day significantly decreases migraine severity.
  • Kovacevic et al (2017) reported that "After 6 months of magnesium prophylaxis, disability due to migraine significantly decreased, whereas physical and psychosocial well-being improved. " This doesn't say that much -- nearly any kind of attention will affect migraine in a positive way.
  • Orr (2014) suggested that "the quality of evidence .. in pediatric migraine prophylaxis is poor".
  • Gallelli et al (2014) reported that "Magnesium increased the efficacy of ibuprofen and acetaminophen."
  • Samaie et al (2012) reported that " Serum Mg level is on average significantly reduced in patients with migraine compared to the healthy group. "
  • Rosanoff et al (2012) stated that "Low magnesium intakes and blood levels have been associated with type 2 diabetes, metabolic syndrome, elevated C-reactive protein, hypertension, atherosclerotic vascular disease, sudden cardiac death, osteoporosis, migraine headache, asthma, and colon cancer."
  • Pringsheim et al (2012) stated that the Canadian headache socieity was among 11 drugs with a "strong recommendation" for migraine prevention, "Based on our review, 11 prophylactic drugs received a strong recommendation for use (topiramate, propranolol, nadolol, metoprolol, amitriptyline, gabapentin, candesartan, butterbur, riboflavin, coenzyme Q10, and magnesium citrate) and 6 received a weak recommendation (divalproex sodium, flunarizine, pizotifen, venlafaxine, verapamil, and lisinopril)." As a comment, many of these medications seem to us to be ineffective (e.g. candesartin, butterbur, riboflavin, co-Q10, lisinopril), and many of the better drugs (e.g. flunarizine, venlafaxine, verapamil) are listed as weak. This makes one question the Canadian headache society's process in this regard.
  • In a metaanalysis, Holland et al (2012) suggested that magnesium was "probably effective" for migraine prevention. This was also reinterated by Schiapparelli et al (2010), and Evers et al (2008).
  • Schurks et al (2008) suggested that magnesium might be particularly useful during pregnancy.
  • Silberstein and Goldberg (2007) suggested that it was useful in menstrual migraine
  • Koseoglu et al (2008) found that 600 mg/day of oral magnesium citrate reduced attack frequency significantly in 30 patients.
  • Bianchi et al (2004) suggested that more controlled studies were needed. This is usually safe to say.
  • Trauninger et al (2002) suggested that migraine patients may have a systemic magnesium deficiency

Evidence for magnesium working as a migraine abortive:

  • Orr(2014) reported that the Canadian headache society recommend "weakly against the use of" ... magnesium. See the comment above about Canadian Headache Society's.
  • Gertsch (2014) did not find substantial effectiveness in pediatric patients given intravenous magnesium.
  • Choi and Parmar reported "The meta-analyses have failed to demonstrate a beneficial effect of intravenous magnesium in terms of reduction in pain relief in acute migraine in adults, showed no benefit in terms of the need for rescue medication and in fact have shown that patients treated with magnesium were significantly more likely to report side-effects/adverse events."
  • Shahrami (2014) found that magnesium was more effective than dexamethasone/metoclopramide. Of course, these latter two medications are not first line migraine abortives, so Shahrami was comparing magnesium to a questionable treatment.
  • Kelly et al(2012) suggested that magnesium is effective in migraine, but it is primarily useful for photophobia and phonophobia.
  • Cete et al (2005) suggested that 2 grams of IV magnesium was similar to placebo.

Proton pump inhibitors (PPI) and magnesium.

Proton pump inhibitors approved in the US include:

  1. omeprazole (Prilosec),
  2. lansoprazole (Prevacid),
  3. rabeprazole (Aciphex),
  4. pantoprazole (Protonix),
  5. esomeprazole (Nexium), and
  6. Zegarid, a rapid release form of omeprazole.

Recent papers showing an association between PPI use and low magnesium include:

  • Danzinger et al (2013) reported that proton pump inhibitors, but not H2 blockers, are associated with hypomagnesemia.
  • Lindner et al (2014) suggested that use of PPI's "predisposes" to hypomagnesia.
  • William et al (2014) suggested that PPI use was associated with lower 24 hour magnesium excretion, possibly related to reduced absorption.

One would think that use of PPI would be correlated with more migraines. This does appear to be true in large studies (e.g. Liang et al, 2014). H2 blockers, such as Ranitidine ("Zantac"), might be less likely to cause headache. So far, there has not been a comparison trial (between PPI and H2 blockers).

Which types of magnesium works best for migraine ?

The goal for magnesium supplements is to have an intake of somewhere between 400 and 600 mg of magnesium/day. Magnesium is a metal, and to be in solution it has to be combined with sometime else - generally a weak organic acid- this might be citrate, malate, oxide, gluconate, glycinate, sulfate, taurate, threonate, etc. Most of these are "just along for the ride". Once the pill dissolves in your stomach, you get the mangesium ion, and whatever it was bound to (e.g. citrate - -citric acid). Magnesium tends to irritate the bowel and for this reason is used as a laxative. It is usually a good idea to combine it with something bland, like calcium. This is the reason why there are many "cal-mag" preparations.

It is doubtful that much magnesium can be absorbed through the skin -- i.e. with lotions, sprays or epson salts. These are probably placebos.

Although magnesium can be given intravenously in very large amounts, it is doubtful that it stays in the body very long, as the kidneys keep the magnesium level regulated. (Swaminathan, 2003)

Concerning the best form of oral magnesium, Swaminathan (2003) states that magnesium gluconate is the best choice, preferably given in divided doses to avoid diarrhea. In our patients, patients often choose to take Cal-Mag, which has calcium included in the tablet, which seems to make it less irritating to the bowel. Magnesium oxide may be slower to be absorbed (perhaps this is good). There doesn't seem to be any science at all about which product works best for migraine. von Luckner and Riederer suggested that Magnesium dicitrate, 600 mg, was the optimum preparation.

The most common preparations are:

  • Nature-made Calcium/magnesium/zinc (only contains 133 mg of magnesium oxide) -- one would need 4 of these/day. The zinc is undesirable here.
  • Calm (many forumulations, a powder that has about 350 mg of magnesium).

Slow-Mag tablets contain 135 mg of Magnesium. These are coated so they dissolve slowly. We do not have anyone taking these. One would think about 4/day would be needed.

One of our patients likes the "Smarty-Pants" gummy magnesium. This product contains quite a bit of other stuff, and it is not a "pure" magnesium product. This adds risk of side effects. It also has 3 grams of sugar, and presumably is not so good for your teeth either.

One would think that one of the many 500 mg magnesium gluconate preparations might work better, if you can find one.

 

Recommendations:

Overall, we agree with the conclusion of Pardutz et al (2012) : "The data available suggest that magnesium has a potential role in the prophylaxis, but the results in acute therapy are far less convincing."

We suggest that most patients with migraine should be taking magnesium 400-600 mg/day.

The main issue that we have encountered with Magnesium intake is indigestion. Preparations with calcium seem to make this less likely.

 

References:

  • Bianchi, A., et al. (2004). "Role of magnesium, coenzyme Q10, riboflavin, and vitamin B12 in migraine prophylaxis." Vitam Horm 69: 297-312.
  • Cete, Y., et al. (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(3): 199-204.
  • Choi, H. and N. Parmar (2014). "The use of intravenous magnesium sulphate for acute migraine: meta-analysis of randomized controlled trials." Eur J Emerg Med 21(1): 2-9.
  • Danziger, J., et al. (2013). "Proton-pump inhibitor use is associated with low serum magnesium concentrations." Kidney Int 83(4): 692-699.
  • Evers, S. (2008). "Treatment of migraine with prophylactic drugs." Expert Opin Pharmacother 9(15): 2565-2573.
  • Gallelli, L., et al. (2014). "Effects of acetaminophen and ibuprofen in children with migraine receiving preventive treatment with magnesium." Headache 54(2): 313-324.
  • Holland, S., Silberstein, S. D., Freitag, F., Dodick, D. W., Argoff, C., & Ashman, E. (2012). Evidence-based guideline update: NSAIDs and other complementary treatments for episodic migraine prevention in adults: Report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology, 78(17), 1346-1353. doi: 10.1212/WNL.0b013e3182535d0c
  • Gertsch, E., et al. (2014). "Intravenous magnesium as acute treatment for headaches: a pediatric case series." J Emerg Med 46(2): 308-312.
  • Kelley, N. E. and D. E. Tepper (2012). "Rescue therapy for acute migraine, part 1: triptans, dihydroergotamine, and magnesium." Headache 52(1): 114-128.
  • Kovacevic, G., et al. (2017). "A 6-month follow-up of disability, quality of life, and depressive and anxiety symptoms in pediatric migraine with magnesium prophylaxis." Magnes Res 30(4): 133-141.
  • Koseoglu, E., et al. (2008). "The effects of magnesium prophylaxis in migraine without aura." Magnes Res 21(2): 101-108.
  • Liang, J. F., et al. (2014). "Proton pump inhibitor-related headaches: A nationwide population-based case-crossover study in Taiwan." Cephalalgia.
  • Lindner, G., et al. (2014). "Impact of proton pump inhibitor use on magnesium homoeostasis: a cross-sectional study in a tertiary emergency department." Int J Clin Pract 68(11): 1352-1357.
  • Orr, S. L. and S. Venkateswaran (2014). "Nutraceuticals in the prophylaxis of pediatric migraine: Evidence-based review and recommendations." Cephalalgia 34(8): 568-583.
  • Pardutz, A. and L. Vecsei (2012). "Should magnesium be given to every migraineur? No." J Neural Transm 119(5): 581-585.
  • Pringsheim, T., et al. (2012). "Canadian Headache Society guideline for migraine prophylaxis." Can J Neurol Sci 39(2 Suppl 2): S1-59.
  • Rosanoff, A., et al. (2012). "Suboptimal magnesium status in the United States: are the health consequences underestimated?" Nutr Rev 70(3): 153-164.
  • Schiapparelli, P., et al. (2010). "Non-pharmacological approach to migraine prophylaxis: part II." Neurol Sci 31 Suppl 1: S137-139.
  • Samaie, A., et al. (2012). "Blood Magnesium levels in migraineurs within and between the headache attacks: a case control study." Pan Afr Med J 11: 46.
  • Schurks, M., et al. (2008). "Update on the prophylaxis of migraine." Curr Treat Options Neurol 10(1): 20-29.
  • Shahrami, A., et al. (2014). "Comparison of Therapeutic Effects of Magnesium Sulfate vs. Dexamethasone/Metoclopramide on Alleviating Acute Migraine Headache." J Emerg Med.
  • Silberstein, S. D. and J. Goldberg (2007). "Menstrually related migraine: breaking the cycle in your clinical practice." J Reprod Med 52(10): 888-895.
  • Sun-Edelstein, C., & Mauskop, A. (2009). Role of magnesium in the pathogenesis and treatment of migraine. Expert Rev Neurother, 9(3), 369-379. doi: 10.1586/14737175.9.3.369
  • Sun-Edelstein, C. and A. Mauskop (2009). "Foods and supplements in the management of migraine headaches." Clin J Pain 25(5): 446-452.
  • Swaminathan R. Magnesium metabolism and its disorders. .Clin Biochem Rev. 2003 May;24(2):47-66
  • Trauninger, A., et al. (2002). "Oral magnesium load test in patients with migraine." Headache 42(2): 114-119.
  • Viering, D., et al. (2017). "Genetic causes of hypomagnesemia, a clinical overview." Pediatr Nephrol 32(7): 1123-1135.
  • von Luckner, A. and F. Riederer (2018). "Magnesium in Migraine Prophylaxis-Is There an Evidence-Based Rationale? A Systematic Review." Headache 58(2): 199-209.
  • William, J. H., et al. (2014). "Proton-Pump Inhibitor use is associated with lower Urinary Magnesium Excretion." Nephrology (Carlton).