The Benefits of Magnesium - A Critical Mineral Nutrient for Health

Although Magnesium receives very little attention from the medical field, this ion is one of the most important electrolytes in neurochemistry because it directly causes our nervous system to relax, shutting off pain and stress signaling pathways: 

1. Magnesium modulates neurological response by deactivating the NMDA (N-Methyl-d-Aspartate) receptor gated ion channel, which is the primary channel that enables potassium and sodium flux and membrane depolarization required to propagate signaling in the nervous system. Without enough available, your nervous system response is always turned on, which encourages chronic pain. (1)
2. It does so extracellularly, that is, adequate magnesium must be present in the extracellular matrix at adequate concentration so as to diffuse into the ion channel and deactivate it to prevent neurological sensitization and inappropriate signaling. Inadequate magnesium levels cause neurological hypersensitivity. (2)
3. Magnesium effectively acts as a cork in NMDA-gated ion channels (6,8-12), preventing excessive Calcium flux and associated oxidative stress (8,13,14) including cell death (15). It has therefore been demonstrated to be neuroprotective.
4. Local, topical, transdermal administration of magnesium has been found to improve pain scores in a variety of clinical trials, including for fibromyalgia. (3)
5. Magnesium is regularly used clinically to relax smooth muscle, epsom salt (MgSO4) for laxative effects for example, prevention of eclampsia during pregnancy (4) and general relaxation in isolation tank treatment.  
6. Magnesium Chloride cream at a very low dose has been found to clinically increase serum levels humans. (5)
7. Magnesium is indispensable in normal metabolism. As neurons are highly metabolically active cells due to the necessity of maintaining and modulating membrane potentials, they require significant production of the body's energy currency, ATP. ATP cannot be produced via respiration without adequate amounts of ionic magnesium, and inadequate magnesium results in a vicious cycle of metabolic dysfunction and destruction. (6) 
8. 99% of body magnesium is found intracellularly, but that’s not where it needs to be to regulate NMDA dynamics. CNS magnesium levels do not track serum magnesium. (16) This may be why local supplementation yields results; it remains extracellular and modulates nervous system response locally. 
9. Magnesium reduces NMDA excitotoxic brain injury in rats.(7) 
10. Magnesium has vast importance in our bodies as a cofactor in activation of hundreds of enzymes and dozens of psychological pathologies, from depression to psychosis. (16) 
    

A concise review of the overall importance of magnesium can be found on the US Government's National Institute of Health Magnesium webpage: 
https://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/ 

Here's an amazing review of magnesium's importance in the central nervous system: https://www.ncbi.nlm.nih.gov/books/NBK507264/pdf/Bookshelf_NBK507264.pdf

References

1. Clarke RJ, Johnson JW, Voltage-dependent gating of NR1/2B NMDA receptors. J. Physiol. 2008;586:5727–5741
2. Sapolsky RM. Stress the aging brain and the mechanisms of neuron death. Cambridge, MA: A Bradford Book, The MIT Press; 1992. p. 192.
3. Engen DJ, McAllister SJ, Whipple MO, Cha SS, Dion Lj, Vincent A, Bauer BA, Wahner-Roedler DL. Effects of transdermal magnesium chloride on quality of life for patients with fibromyalgia, a feasibility study.  Journal of Integrative Medicine, Volume 12 Issue 5, September 2015, 306-313. 
4. Chesley LC, Hypertensive disorders in pregnancy, Appleton-Century-Crofts, New york, 1978
5. Kass L., Rosanoff A., Tanner A., Sullivan K., McAuley W., Plesset M. Effect of transdermal magnesium cream on serum and urinary magnesium levels in humans: A pilot study. PLoS ONE. 2017;12:e0174817.
6. Bear MF, Connors BW, Paradiso MA. Neurotransmitter systems. In: Neuroscience exploring the brain. Baltimore, MD: Lippincott Williams and Wilkins; 2001. p. 131–62.
7. McDonald JW, Silverstein FS, Johnston MV. Magnesium reduces N-methyl-D-aspartate (NMDA)-mediated brain injury in perinatal rats, Neuroscience Letters, 109 (1990) 234-238
8. Mark LP, Prost RW, Ulmer JL, et al. Pictorial review of glutamate excitotoxicity: fundamental concepts for neuroimaging. AJNR Am J Neuroradiol 2001;22:1813–24.
9. Kandel ER, Schwartz JH, Jessell TM. Synaptic integration. In: Essentials of neural science and behavior. Stamford, CT: Appleton and Lange; 1995. p. 219–41.
10. McMenimen KA, Dougherty DA, Lester HA, Petersson EJ. Probing the Mg2+ blockade site of an N-methyl-D-aspartate (NMDA) receptor with unnatural amino acid mutagenesis. ACS Chem Biol 2006;1:227–34.
11. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Molecular biology of the cell. 4th ed. New York, NY: Garland Science; 2002. p. 615–58.
12. Decollogne S, Tomas A, Lecerf C, Adamowicz E, Seman M. NMDA receptor complex blockade by oral administration of magnesium: comparison with MK-801. Pharmacol Biochem Behav 1997;58:261–8. 
13. Blaylock RL. Food additive excitotoxins and degenerative brain disorders. Med Sentinel 1999;4:212–5.
14. Carafoli E. Calcium – a universal carrier of biological signals. FEBS J 2005;272:1073–89.
15. Gillessen T, Budd SL, Lipton SA. Excitatory amino acid neurotoxicity. In: Alzheimer C, editor. Molecular and cellular biology of neuroprotection in the CNS series: advances in experimental medicine and biology, vol. 513. New York, NY: Kluwer Academic/Plenum Publishers, Georgetown, TX: Landes Bioscience; 2002. p. 3–40.
16. Eby GA, Eby KL Magnesium for treatment-resistant depression: A review and hypothesis Medical Hypotheses 74 (2010) 649-660