Evidence of benefit
81 patients aged 18-65 years with average migraine episodes of 3.6 per month received 600 mg oral magnesium (trimagnesium dicitrate) daily for 12 weeks or a placebo. In weeks 9-12 the attack frequency was reduced by 41.6% in the magnesium group and by 15.8% in the placebo group. The number of days with migraine and drug consumption also decreased significantly in the magnesium group. Peikert A, Wilimzig C, Kohne-Volland R. Prophylaxis of migraine with oral magnesium: results from a prospective, multi-center, placebo-controlled and double-blind randomized study. Cephalalgia. 1996;16:257-263.

In a double blind, randomised, placebo controlled study 30 patients with migraine without aura (20-55 years old with 2-5 migraine attacks per month) were given 600 mg a day oral magnesium citrate. Compared with those of 10 patients with similar properties on placebo treatment, migraine attack frequency, severity and P1 amplitude in the magnesium treatment group were found to be significantly lower than those in placebo treatment group. Cortical blood flow in inferolateral frontal, inferolateral temporal and insular regions increased significantly after magnesium treatment while such significant changes of cortical blood flow were not observed with placebo treatment. Köseoglu E, Talaslioglu A, Gönül AS, Kula M. The effects of magnesium prophylaxis in migraine without aura. Magnes Res. 2008 Jun;21(2):101-8.

A doubleblind, cross-over multicenter pilot study with 43 migraine patients given 600 mg magnesium daily in the form of trimagnesium dicitrate saw a significant reduction in the incidence of migraine attacks. The authors state that although the level of effectiveness of magnesium therapy “does not appear to be as high as that of presently approved migraine prophylactic substances, a very low rate of side effects can be expected.” Taubert K. [Magnesium in migraine. Results of a multicenter pilot study] [Article in German] Fortschr Med. 1994 Aug 30;112(24):328-30.

Not all studies have demonstrated a positive effect. A multicentre, prospective, randomised, double-blind, placebo-controlled study with 69 patients aged 18-64 years with two to six migraine attacks per month without aura, and history of migraine of at least 2 years used 10 mmol (240 mg) magnesium twice-daily (total 480 mg) or placebo. No difference was seen between the treatment and the placebo group with 10 from each group seeing reduction in intensity or duration of migraine attacks (28.6% under magnesium and 29.4% under placebo). Pfaffenrath V, Wessely P, Meyer C, Isler HR, Evers S, Grotemeyer KH, Taneri Z, Soyka D, Göbel H, Fischer M. Magnesium in the prophylaxis of migraine--a double-blind placebo-controlled study. Cephalalgia. 1996 Oct;16(6):436-40. However, the target, a “reduction of at least 50% in intensity or duration of migraine attacks” was larger than that obtained in Peikert et.al (detailed above) which showed reduction of 41.6% in attacks from 600 mg magnesium a day compared to the placebo group which showed 15.8%.

Study with children ages 3 to 17 years - Subjects were randomly assigned to receive either magnesium oxide (9 mg/kg per day by mouth divided 3 times a day with food) (n = 58) or matching placebo (n = 60) for 16 weeks. The researchers found a statistically significant decrease over time in headache frequency in the magnesium oxide group but not in the placebo group. The group treated with magnesium oxide had significantly lower headache severity relative to the placebo group. However the authors concluded that “this study does not unequivocally determine whether oral magnesium oxide is or is not superior to placebo in preventing frequent migrainous headache in children, but treatment with the active agent did lead to a significant reduction in headache days.” Wang F, Van Den Eeden SK, Ackerson LM, et al. Oral magnesium oxide prophylaxis of frequent migrainous headache in children: a randomized, double-blind, placebo-controlled trial. Headache. 2003;43:601-610.

Other studies
Intravenous therapy –
A randomised, double-blind, placebo-controlled study assigned 120 patients at random to receive magnesium sulphate, 1000 mg intravenously, or placebo saline, 10 ml. The migraine with aura group patients receiving magnesium sulphate presented a statistically significant improvement of pain and of all associated symptoms compared with controls. The analgesic therapeutic gain was 36.7% at 1 h. Bigal ME, Bordini CA, Tepper SJ, Speciali JG. Intravenous magnesium sulphate in the acute treatment of migraine without aura and migraine with aura. A randomized, double-blind, placebo-controlled study. Cephalalgia. 2002 Jun;22(5):345-53. A similar trial with 15 patients on the same dosage demonstrated that “The pain disappeared in 13 patients (86.6%); it was diminished in 2 patients (13.4%); and in all 15 patients (100%), accompanying symptoms disappeared. In the placebo group, a decrease in pain severity but persisting nausea, irritability, and photophobia were noted in 1 patient (6.6%). Accompanying symptoms disappeared in 3 patients (20%) 30 minutes after placebo administration.” Demirkaya S, Vural O, Dora B, Topçuoğlu MA. Efficacy of intravenous magnesium sulfate in the treatment of acute migraine attacks. Headache. 2001 Feb;41(2):171-7. 40 patients, intravenous infusion of 1 gram of magnesium sulphate. Complete elimination of pain was observed in 80% of the patients within 15 minutes of infusion. No recurrence or worsening of pain was observed within 24 hours in 56% of the patients. Mauskop A, Altura BT, Cracco RQ, Altura BM. Intravenous magnesium sulfate rapidly alleviates headaches of various types. Headache. 1996 Mar;36(3):154-60.

Menstrual migraine –
20 patients affected by menstrual migraine, in a double-blind, placebo controlled study were given 360 mg a day of magnesium or placebo from the 15th day of the cycle and continued till the next menses, for two months. The number of days with headache was reduced only in the patients on active drug. Facchinetti F, Sances G, Borella P, Genazzani AR, Nappi G. Magnesium prophylaxis of menstrual migraine: effects on intracellular magnesium. Headache. 1991 May;31(5):298-301.

Migraine and low magnesium –
A lower migraine threshold could be related to magnesium deficiency. Facchinetti F, Sances G, Borella P, Genazzani AR, Nappi G. Magnesium prophylaxis of menstrual migraine: effects on intracellular magnesium. Headache. 1991 May;31(5):298-301. “The available evidence suggests that up to 50% of patients during an acute migraine attack have lowered levels of ionized magnesium. Infusion of magnesium results in a rapid and sustained relief of an acute migraine in such patients.” Mauskop A, Altura BM. Role of magnesium in the pathogenesis and treatment of migraines. Clin Neurosci. 1998;5(1):24-7. Serum and salivary magnesium levels were measured in juvenile migraine patients. In comparison with normal subjects, migraine patients had lower levels of serum and salivary magnesium interictally. Serum magnesium levels tended to be further reduced during attacks. Gallai V, Sarchielli P, Coata G, Firenze C, Morucci P, Abbritti G. Serum and salivary magnesium levels in migraine. Results in a group of juvenile patients.  Headache. 1992 Mar;32(3):132-5. In the study where 40 patients were given intravenous infusion of 1 gram of magnesium sulphate Immediate pain relief was observed in 32 (80%) of 40 patients. In 18 of the 32 patients, pain relief persisted for at least 24 hours. Of these 18 patients, 16 (89%) had a low serum IMg2+ level. Of the 8 patients with no relief, only 37.5% had a low IMg2+ level. Mauskop A, Altura BT, Cracco RQ, Altura BM. Intravenous magnesium sulfate rapidly alleviates headaches of various types. Headache. 1996 Mar;36(3):154-60.

Food sources
Almonds, dry roasted, 80 mg per ounce; Cashews, dry roasted, 70 mg per ounce; Cereal, shredded wheat, 2 rectangular biscuits, 55 mg; Potato, baked w/ skin, 1 medium 50mg. http://ods.od.nih.gov/factsheets/magnesium.asp

Bioavailability / content
Urinary magnesium excretion of normal volunteers given different formulations. Results indicated relatively poor bioavailability of magnesium oxide (fractional absorption 4 per cent) but significantly higher and equivalent bioavailability of magnesium chloride, magnesium lactate and magnesium aspartate. Firoz M, Graber M. Bioavailability of US commercial magnesium preparations. Magnes Res. 2001 Dec;14(4):257-62.

Study compared magnesium oxide and magnesium citrate with respect to in vitro solubility and in vivo gastrointestinal absorbability. Magnesium oxide was virtually insoluble in water and only 43% soluble in simulated peak acid secretion. Magnesium citrate had high solubility even in water (55%) and was substantially more soluble than magnesium oxide in all states of acid secretion. Magnesium absorption from the two magnesium salts was measured in vivo in normal volunteers by assessing the rise in urinary magnesium following oral magnesium load. The increment in urinary magnesium following magnesium citrate load was significantly higher than that obtained from magnesium oxide load. Lindberg JS, Zobitz MM, Poindexter JR, Pak CY. Magnesium bioavailability from magnesium citrate and magnesium oxide. J Am Coll Nutr. 1990 Feb;9(1):48-55.

Percent magnesium content of oral supplements – Magnesium Oxide – 60%; Magnesium citrate – 16%; magnesium lactate – 12%; magnesium sulphate – 10%. Klasco RK (Ed): USP DI® Drug Information for the Healthcare Professional. Thomson MICROMEDEX, Greenwood Village, Colorado 2003. Cited in Office of Dietary Supplements. Dietary Supplement Fact Sheet – Magnesium. http://ods.od.nih.gov/factsheets/magnesium.asp#en28

Safety
Study using intravenous 1000mg magnesium showed 26 patients (86.6%) with mild side effects “which did not necessitate discontinuing treatment during magnesium sulfate administration.” Demirkaya S, Vural O, Dora B, Topçuoğlu MA. Efficacy of intravenous magnesium sulfate in the treatment of acute migraine attacks. Headache. 2001 Feb;41(2):171-7.  With 480 mg daily, 45.7% of patients taking magnesium reported primarily mild adverse events like soft stool and diarrhoea in contrast to 23.5% of those taking placebo. Pfaffenrath V, Wessely P, Meyer C, Isler HR, Evers S, Grotemeyer KH, Taneri Z, Soyka D, Göbel H, Fischer M. Magnesium in the prophylaxis of migraine--a double-blind placebo-controlled study. Cephalalgia. 1996 Oct;16(6):436-40.

There is no evidence of adverse effects from the consumption of naturally occurring magnesium in foods. Adverse effects from magnesium containing supplements may include osmotic diarrhea. The UL (the maximum daily intake unlikely to result in adverse health effects) for magnesium represents intake from a pharmacological agent only and does not include intake from food and water. Food and Nutrition Board, Institute of Medicine. DRI Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, DC: National Academy Press; 1997. http://www.iom.edu/Object.File/Master/7/294/0.pdf

We report a case of hypermagnesemia following massive Epsom salt ingestion that resulted in extreme musculoskeletal weakness and altered mentation. Signs and symptoms of this condition include extreme muscle weakness, loss of deep tendon reflexes, mental status depression, and cardiac dysrhythmias. Clinically significant hypermagnesemia following oral or rectal administration of magnesium containing products in patients with normal renal function is rare. Nordt SP, Williams SR, Turchen S, Manoguerra A, Smith D, Clark RF. Hypermagnesemia following an acute ingestion of Epsom salt in a patient with normal renal function. J Toxicol Clin Toxicol. 1996;34(6):735-9.

We reported a case of hypermagnesemia in whom hypotension, hypothermia, and coma developed after repetitive doses of a seemingly harmless antacid for epigastric pain following bone marrow transplantation. The highest measured magnesium concentration was 5.9 mmol/l. She recovered without dialysis. The patient's condition improved with intravenous doses of calcium gluconate, saline solution infusion, and cardiovascular support. Jaing TH, Hung IJ, Chung HT, Lai CH, Liu WM, Chang KW. Acute hypermagnesemia: a rare complication of antacid administration after bone marrow transplantation. Clin Chim Acta. 2002 Dec;326(1-2):201-3. (Normal blood levels of magnesium - 1.5 - 2.0 mmol/l)

Interaction with other drugs
Weak interaction with Aspirin: Shechter M, Merz CN, Paul-Labrador M, Meisel SR, Rude RK, Molloy MD, Dwyer JH, Shah PK, Kaul S. Oral magnesium supplementation inhibits platelet-dependent thrombosis in patients with coronary artery disease.  Am J Cardiol. 1999 Jul 15;84(2):152-6. Also Zinc supplements of 142 mg/day decreased magnesium absorption:  Spencer H, Norris C, Williams D. Inhibitory effects of zinc on magnesium balance and magnesium absorption in man. J Am Coll Nutr. 1994 Oct;13(5):479-84.

Thanks again so very much, Jamil for this very, very useful and well researched info on migraine treatment with magnesium!!  I think that I will look into this for my son.  Definitely worth it!!

Hope all is well with you!
Gretchen