"Natural" or Alternative Medications for Migraine Prevention

Randolph W. Evans, MD; Frederick R. Taylor, MD


Headache. 2006;46(6):1012-1018. 

In This Article


Low brain magnesium levels have been reported in at least 8 studies involving migraineurs. At least 4 trials of magnesium as prophylactic therapy for migraine have been conducted, along with trials investigating magnesium as an acute treatment for migraine. The published trials have yielded mixed results, with favorable effects reported for acute treatment of patients with aura and, possibly, perimenstrual migraine prophylaxis. The magnesium formulation used has varied, and no study has compared different magnesium formulations with similar dosages of Mg++ to determine whether formulation type has clinical relevance. Magnesium's efficacy as an acute therapy may relate to ionized Mg++ levels, and it appears that prolonged "high dose" supplementation for a minimum of 3 to 4 months may be required to achieve any benefit from prophylactic therapy. Due to inconsistent findings from multiple trials, the evidence level for magnesium in prevention of migraine is Grade B.

Again, several reports have indicated that low levels of intracellular magnesium ion and serum ionized magnesium may correlate with the agent's efficacy, and the conflicting results from migraine treatment of subjects either likely to respond (low levels) or unlikely to respond (normal levels).[30,31,32,33] Even should this variable be adequately accounted for in future research, there is another that appears problematic. In a study designed to determine magnesium effects on sumatriptan nonresponders (83% of whom had low ionized magnesium levels), Cady et al found that although ionized magnesium levels could be normalized intravenously, a daily dose of 250 mg of oral magnesium taurate for 5½ months failed to maintain normal levels.[34] Mauskop has recommended a daily dose of 600 mg of chelated or slow-release oral magnesium for sustained supplementation.[35]

The first RCT of magnesium for migraine prevention involved only 20 subjects and was positive; the active therapy was 360 mg Mg++ pyrrolidone carboxylic acid divided TID.[30] The second RCT, by Peikert et al, involved 81 adult women and 600 mg magnesium (trimagnesium dicitrate) daily demonstrated a 41.6% improvement with verum versus 15.8% for placebo.[36] The third RCT for migraine prophylaxis, published by Pfafferath et al, involved 69 patients taking 486 mg magnesium; no benefit for magnesium was found; at the end of the 3-month treatment phase, the responder rate was 28.6% in the magnesium group and 29.4% in placebo subjects, according to the primary efficacy endpoint. Diarrhea was reported in significant numbers of both patients receiving placebo (23.5%) and patients receiving magnesium (45.7%); the high rate in the active arms suggests that a poorly absorbed magnesium preparation lent to the negative outcome.[37,38] In a last trial, Wang et al gave magnesium oxide 9 mg/kg divided TID to subjects aged 3 to 17 years.[39] Approximately three-quarters of eligible subjects completed the study, with a significant downward trend in headache days in the active treatment group versus placebo; the lack of any difference in the slope of treatment trends, however, was such that no significant superiority of magnesium over placebo could be documented.

Adverse events reported consequent to magnesium therapy have been mainly gastrointestinal (diarrhea predominating). There is no evidence of any short- or long-term safety issues for individuals taking magnesium in the absence of serious renal disease.


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