Efficacy of magnesium supplementation in the prophylaxis of migraine: a systematic review of clinical trials comparing oral magnesium to placebo or standard care

Abstract

Abstract Background Migraine remains a significant global burden, necessitating effective non-pharmacological alternatives. Magnesium plays a critical role in migraine pathophysiology through NMDA receptor blockade, neurotransmitter regulation, and the inhibition of cortical spreading depression. However, clinical data remain contradictory, particularly regarding the efficacy of various magnesium salts. Objective This systematic review evaluates the efficacy and safety of oral magnesium supplementation compared to placebo or standard care (sodium valproate) for migraine prophylaxis. Methods We analyzed randomized, double-blind trials and crossover studies involving diverse populations in Germany, Iran, Italy, and Turkey. Interventions included daily doses of 360–600 mg across multiple formulations: magnesium dicitrate, oxide, aspartate, and pyrrolidone carboxylic acid. Results Efficacy varied significantly by formulation. Trimagnesium dicitrate (600 mg/day) significantly reduced attack frequency and severity compared to placebo ( p < 0.05). Conversely, magnesium aspartate failed to demonstrate superiority over placebo, necessitating early study discontinuation. In active-comparator trials, 500 mg of magnesium oxide demonstrated efficacy similar to sodium valproate. Furthermore, concurrent magnesium and valproate therapy significantly outperformed valproate monotherapy. The most common adverse effects were gastrointestinal, including diarrhea (up to 18.6%) and soft stools. Conclusion Oral magnesium, particularly in citrate or oxide forms at 500–600 mg daily, is an effective and safe prophylactic option. While gastrointestinal side effects may limit adherence, magnesium remains a viable alternative or adjunct to standard pharmacological treatments.