By: Seethal Sara Thomas, FNP-BC
Migraine is a debilitating disease with social and financial implications for the individual and society. Magnesium is an increasingly accepted treatment option for migraine with a generally low side effect profile when used in appropriate doses. Magnesium is the second most abundant cation within the body’s cells and 98-99% is in intracellular fluid, while only 1-2% is present in blood and extracellular fluids (Fiorentini, et al., 2021). Magnesium has a major role in many physiologic functions, but due to such a low percentage of total magnesium concentration being in the blood, it is difficult to assess magnesium status with a serum blood test and a normal level of serum magnesium does not rule out magnesium deficiency (Fiorentini, et al., 2021). Magnesium is involved in many functions of the body and is a cofactor for over 600 enzymes and an activator for an additional 200 enzymes. Magnesium is involved in bone development, neuromuscular function, signaling pathways, energy storage and transfer, glucose, lipid and protein metabolism, DNA and RNA stability, and cell proliferation (Fiorentini, et al., 2021). About 50% of the US population consumes less than the required amount of magnesium. A red blood cell magnesium test offers a more accurate assessment of magnesium status (Razzaque, 2018).
One of the main neurological functions of magnesium is due to magnesium’s interaction with the N-methyl-D-aspartate (NMDA) receptor. At a normal membrane potential, magnesium ions block NMDA receptors. When magnesium concentration is reduced, less NMDA channels are blocked and this increased excitatory postsynaptic potential causes hyperexcitability of the neurons, which can lead to oxidative stress and neuronal cell death (Fiorentini, et al., 2021). Magnesium's pain-relieving effects are through antagonism of the N-methyl-D-aspartate (NMDA) receptor and inhibiting calcium channels and calcium influx (Miller, et al., 2019).
Magnesium sulfate is reported to have been used in the medical field as early as 1600s, but application for magnesium sulfate by the FDA happened almost 400 years later and research regarding magnesium treatments and nutrition is still ongoing (Miller, et al., 2019). Studies suggest that magnesium deficiency is an independent risk factor for acute migraine and decreased levels of magnesium increase the probability of having acute migraine (Maier, et al., 2020). The type, dose, and duration of magnesium treatment has not been standardized yet for acute migraine treatment. Magnesium pidolate, magnesium citrate, magnesium sulfate, magnesium oxide, and magnesium dicitrate have shown clinical significance and safety for treatment of acute migraine (Miller, et al., 2019). Though still a developing area of research, the evidence does not support a certain magnesium formulation for being more bioavailable (Razzaque, 2018). In clinical practice, for acute migraine IV magnesium sulfate 1-2 grams is often available to offer as treatment. The American Academy of Neurology supports the effectiveness of oral magnesium for migraine prophylaxis and suggests IV magnesium routinely be used for acute migraine (Fiorentini, et al., 2021). In a study testing migraine with aura symptoms relief with magnesium or placebo, 100% of patients improved after IV magnesium sulfate administration while only 7% improved with placebo. The placebo group was administered IV magnesium after the placebo and their symptoms improved. For the magnesium sulfate only group, all patients had a decrease in pain and all patients had full resolution of associated symptoms (Demirkaya, et al, 2004). This particular study only had 15 participants, but it demonstrates magnesium sulfate was superior to placebo (Demirkaya, et al, 2004). Magnesium due to effectiveness and safety should not be forgotten as a last resort if all other treatments have failed. It could be used earlier to mitigate the need for rescues analgesia, but magnesium’s analgesic effect is not limited to early treatment. In a study evaluating traumatic headache, the need for rescue analgesia at any point was improved with magnesium sulfate and improved the migraine symptoms for over 1 hour (Miller, et al., 2019).
Magnesium has evidence to demonstrate that it is effective for migraine prophylaxis as well as acute migraine treatment. More availability of accurate testing measures for deficiency could help further research into acute treatment, dietary needs, migraine prophylaxis, and help rule out deficiency (Razzaque, 2018).
References
Demirkaya, S., Vural, O., Dora, B., & Topcuoglu, M. A. (2004). Efficacy of Intravenous Magnesium Sulfate in the Treatment of Acute Migraine Attacks. Headache: The Journal of Head and Face Pain, 41(2), 171–177. https://doi.org/10.1046/j.1526-4610.2001.111006171.x
Fiorentini, D., Cappadone, C., Farruggia, G., & Prata, C. (2021). Magnesium: Biochemistry,
Nutrition, Detection, and Social Impact of Diseases Linked to Its Deficiency. Nutrients, 13(4), 1136. https://doi.org/10.3390/nu13041136
Maier, J. A., Pickering, G., Giacomoni, E., Cazzaniga, A., & Pellegrino, P. (2020). Headaches and Magnesium: Mechanisms, Bioavailability, Therapeutic Efficacy and Potential Advantage of Magnesium Pidolate. Nutrients, 12(9), 2660. https://doi.org/10.3390/nu12092660
Miller, A. C., K. Pfeffer, B., Lawson, M. R., Sewell, K. A., King, A. R., & Zehtabchi, S. (2019). Intravenous Magnesium Sulfate to Treat Acute Headaches in the Emergency Department: A Systematic Review. Headache: The Journal of Head and Face Pain, 59(10), 1674–1686. https://doi.org/10.1111/head.13648
Razzaque M. S. (2018). Magnesium: Are We Consuming Enough?. Nutrients, 10(12), 1863. https://doi.org/10.3390/nu10121863|| Assessed and Endorsed by the MedReport Medical Review Board
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