Magnesium plays a key role in regulating both blood vessel size and the rate at which cells burn energy. It also affects a variety of headache-related receptors and neurotransmitters including serotonin receptors, nitric oxide synthesis and release and NMDA receptors. Evidence suggests that up to 50% of chronic severe headache patients experience decreased levels of ionized magnesium during an acute attack. Infusion of magnesium results in a rapid and sustained relief of acute headache pain in these patients. Several studies suggest that chronic oral magnesium supplementation may also reduce the frequency of headaches.