The Effect of Magnesium Deficiency on Neurological Disorders: A Narrative Review Article
Abstract
Background: Magnesium (Mg) is an essential element for the body. It is a cofactor for ATP, DNA, and RNA and more than 600 enzymes. As it is similar to Ca2+, this element can also act as a cell signaling molecule and play multiple important roles in the nervous, muscle, and immune systems. Recent studies have associated Mg-deficiency with many neurological disorders, such as cerebral vasospasm, Alzheimer’s disease, stroke, and migraine. As it plays such a crucial role in human body, therefore, we summarized the role of Mg in neurological disorders to illustrate the symptoms caused by Mg-deficiency and the possible underlying mechanisms.
Methods: We critically discuss the role of it that we review the recent literature of magnesium. We also review the available data which are concerning the role of magnesium in neurological disorders.
Results: Magnesium is related to neurological disorders on the basis of the study of animals and humans experiments. Furthermore, these nervous systems related diseases include cerebral vasospasm, Alzheimer’s disease, Parkinson’s disease, stroke and migraine.
Conclusion: Magnesium has effects on neurological disorders, such as its utility in cerebral vasospasm, Alzheimer’s disease, Parkinson’s disease, stroke and migraine. So here we make a brief review to conclude it.
1. Volpe SL (2015). Magnesium and the Athlete. Curr Sports Med Rep, 14(4): 279-83.
2. Grober U, Schmidt J, Kisters K (2015). Magnesium in Prevention and Therapy. Nutrients, 7(9): 8199-226.
3. Vink R (2016). Magnesium in the CNS: recent advances and developments. Magnes Res, 29(3): 95-101.
4. Slutsky I, Abumaria N, Wu L J et al (2010). Enhancement of learning and memory by elevating brain magnesium. Neuron, 65(2): 165-77.
5. Libien J, Sacktor T C,Kass I S (2005). Magnesium blocks the loss of protein kinase C, leads to a transient translocation of PKC(alpha) and PKC(epsilon), and improves recovery after anoxia in rat hippocampal slices. Brain Res Mol Brain Res, 136(1-2): 104-11.
6. Mayer M L, Westbrook G L,Guthrie P B (1984). Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones. Nature, 309(5965):261-3.
7. Nowak L, Bregestovski P, Ascher P et al (1984). Magnesium gates glutamate-activated channels in mouse central neurones. Nature, 307(5950):462-5.
8. Gums J G (2004). Magnesium in cardiovascular and other disorders. Am J Health Syst Pharm, 61(15):1569-76.
9. Altura B,Altura B (2016). Importance of ionized magnesium measurements in physiology and medicine and the need for ion-selective electrodes. J Clin Case Stu, 1(2): doi https://www.sciforschenonline.org/journals/clinical-case-studies/JCCS-1-111.php
10. Vormann J, Anke M (2002). Dietary magnesium: supply, requirements and recommendations-results from duplicate and balance studies in man. J Clin Basic Cardiol, 5:49-53.
11. Azoulay A, Garzon P,Eisenberg MJ (2001). Comparison of the mineral content of tap water and bottled waters. J Gen Intern Med, 16(3): 168-75.
12. Murck H (2002). Magnesium and affective disorders. Nutr Neurosci, 5(6): 375-89.
13. Chang JJ, Mack WJ, Saver JL, Sanossian N (2014). Magnesium: potential roles in neurovascular disease. Front Neurol, 5: 52.
14. Jahnen-Dechent W, Ketteler M (2012). Magnesium basics. Clin Kidney J, 5(Suppl 1):i3-i14..
15. Findlay JM, Nisar J, Darsaut T (2016). Cerebral Vasospasm: A Review. Can J Neurol Sci, 43: 15-32.
16. Farago M, Szabo C, Dora E et al (1991). Contractile and endothelium-dependent dilatory responses of cerebral arteries at various extracellular magnesium concentrations. J Cereb Blood Flow Metab, 11(1): 161-4.
17. Hanline M Jr (1985). Hypomagnesemia causes coronary artery spasm. JAMA, 253(3):342.
18. Keith W. Muir (2000). Therapeutic potential of magnesium in the treatment of acute stroke. J Stroke Cerebrovasc Dis, 9(6): 257-67.
19. Longstreth WT Jr, Fahrenbruch CE, Olsufka M et al (2002). Randomized clinical trial of magnesium, diazepam, or both after out-of-hospital cardiac arrest. Neurology, 59(4):506-14.
20. Treggiari-Venzi MM, Suter PM, Romand JA (2001). Review of medical prevention of vasospasm after aneurysmal subarachnoid hemorrhage: a problem of neurointensive care. Neurosurgery, 48(2): 249-62.
21. Westermaier T, Zausinger S, Baethmann A,Schmid-Elsaesser R (2005). Dose finding study of intravenous magnesium sulphate in transient focal cerebral ischemia in rats. Acta Neurochir (Wien), 147(5): 525-32.
22. Stippler M, Crago E, Levy EI et al (2006). Magnesium infusion for vasospasm prophylaxis after subarachnoid hemorrhage. J Neurosurg, 105(5):723-9.
23. Fann DY, Lee SY, Manzanero S et al (2013). Pathogenesis of acute stroke and the role of inflammasomes. Ageing Res Rev, 12(4): 941-66.
24. Adeoye O, Hornung R, Khatri P, Kleindorfer D (2011). Recombinant tissue-type plasminogen activator use for ischemic stroke in the United States: a doubling of treatment rates over the course of 5 years. Stroke, 42(7): 1952-5.
25. Saver J L (2011). Improving reperfusion therapy for acute ischaemic stroke. J Thromb Haemost, 9 Suppl 1:333-43.
26. Muir KW, Lees KR, Ford I et al (2004). Magnesium for acute stroke (Intravenous Magnesium Efficacy in Stroke trial): randomised controlled trial. Lancet, 363(9407): 439-45.
27. Pan W H, Lai Y H, Yeh W T et al (2017). Intake of potassium- and magnesium-enriched salt improves functional outcome after stroke: a randomized, multicenter, double-blind controlled trial. Am J Clin Nutr, 106(5): 1267-73.
28. Ferre S, Mazur A, Maier J A (2007). Low-magnesium induces senescent features in cultured human endothelial cells. Magnes Res, 20(1): 66-71.
29. Wolf F I, Trapani V, Simonacci M et al (2008). Magnesium deficiency and endothelial dysfunction: is oxidative stress involved? Magnes Res, 21(1): 58-64.
30. Larsson SC, Orsini N, Wolk A (2012). Dietary magnesium intake and risk of stroke: a meta-analysis of prospective studies. Am J Clin Nutr, 95(2): 362-6.
31. Volpe SL (2013). Magnesium in disease prevention and overall health. Adv Nutr, 4(3): 378S-83S.
32. Lin JY, Chung SY, Lin M C, Cheng F C (2002). Effects of magnesium sulfate on energy metabolites and glutamate in the cortex during focal cerebral ischemia and reperfusion in the gerbil monitored by a dual-probe microdialysis technique. Life Sci, 71(7): 803-11.
33. Sharp FR, Lu A, Tang Y, Millhorn D E (2000). Multiple molecular penumbras after focal cerebral ischemia. J Cereb Blood Flow Metab, 20(7): 1011-32.
34. Heiss W D, Thiel A, Grond M,Graf R (1999). Which targets are relevant for therapy of acute ischemic stroke? Stroke, 30(7):1486-9.
35. Lipton P (1999). Ischemic cell death in brain neurons. Physiol Rev, 79(4): 1431-568.
36. Mori K, Yamamoto T, Nakao Y et al (2009). Initial clinical experience of vasodilatory effect of intra-cisternal infusion of magnesium sulfate for the treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Neurol Med Chir (Tokyo), 49(4): 139-45.
37. Adebamowo S N, Spiegelman D, Willett W C, Rexrode K M (2015). Association between intakes of magnesium, potassium, and calcium and risk of stroke: 2 cohorts of US women and updated meta-analyses. Am J Clin Nutr, 101(6): 1269-77.
38. Grundke-Iqbal I, Iqbal K, Tung YC et al (1986). Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci U S A, 83(13): 4913-7.
39. Gandy S,Greengard P (1992). Amyloidogenesis in Alzheimer's disease: some possible therapeutic opportunities. Trends Pharmacol Sci, 13(3):108-13.
40. LaFerla F M,Oddo S (2005). Alzheimer's disease: Abeta, tau and synaptic dysfunction. Trends Mol Med, 11(4):170-6.
41. Prince M, Bryce R, Albanese E et al (2013). The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement, 9(1):63-75.e2.
42. Fan X, Wheatley EG,Villeda SA (2017). Mechanisms of Hippocampal Aging and the Potential for Rejuvenation. Annu Rev Neurosci, 40: 251-72.
43. Durlach J (1990). Magnesium depletion and pathogenesis of Alzheimer's disease. Magnes Res, 3(3): 217-8.
44. Barbagallo M, Belvedere M, Di Bella G et al (2011). Altered ionized magnesium levels in mild-to-moderate Alzheimer's disease. Magnes Res, 24(3): S115-21.
45. Xu Z P, Li L, Bao J et al (2014). Magnesium protects cognitive functions and synaptic plasticity in streptozotocin-induced sporadic Alzheimer's model. PLoS One, 9(9):e108645.
46. Hampel H, Mitchell A, Blennow K et al (2004). Core biological marker candidates of Alzheimer's disease - perspectives for diagnosis, prediction of outcome and reflection of biological activity. J Neural Transm (Vienna), 111(3): 247-72.
47. Sherer T B, Betarbet R, Testa C M et al (2003). Mechanism of toxicity in rotenone models of Parkinson's disease. J Neurosci, 23(34): 10756-64.
48. Conway KA, Lee SJ, Rochet JC et al (2000). Acceleration of oligomerization, not fibrillization, is a shared property of both alpha-synuclein mutations linked to early-onset Parkinson's disease: implications for pathogenesis and therapy. Proc Natl Acad Sci U S A, 97(2): 571-6.
49. Golts N, Snyder H, Frasier M et al (2002). Magnesium inhibits spontaneous and iron-induced aggregation of alpha-synuclein. J Biol Chem, 277(18):16116-23.
50. Yasui M, Kihira T,Ota K (1992). Calcium, magnesium and aluminum concentrations in Parkinson's disease. Neurotoxicology, 13(3): 593-600.
51. Forte G, Alimonti A, Violante N et al (2005). Calcium, copper, iron, magnesium, silicon and zinc content of hair in Parkinson's disease. J Trace Elem Med Biol, 19(2-3): 195-201.
52. Silberstein SD (2004). Migraine. Lancet, 363(9406):381-91.
53. Olesen J, Steiner T J (2004). The International classification of headache disorders, 2nd edn (ICDH-II). J Neurol Neurosurg Psychiatry, 75(6): 808-11.
54. Clifford Rose F (1991). The pathogenesis of migraine. J R Soc Med, 84(9):519-21.
55. Daniel O, Mauskop A (2016). Nutraceuticals in Acute and Prophylactic Treatment of Migraine. Curr Treat Options Neurol, 18(4):14.
56. Talebi M, Savadi-Oskouei D, Farhoudi M et al (2011). Relation between serum magnesium level and migraine attacks. Neurosciences (Riyadh), 16(4): 320-3.
57. Demirkaya S, Vural O, Dora B, Topcuoglu MA (2001). Efficacy of intravenous magnesium sulfate in the treatment of acute migraine attacks. Headache, 41(2): 171-7.
58. Trauninger A, Pfund Z, Koszegi T, Czopf J (2002). Oral magnesium load test in patients with migraine. Headache, 42(2): 114-9.
59. Schurks M, Rist PM, Bigal ME et al (2009). Migraine and cardiovascular disease: systematic review and meta-analysis. BMJ, 339: b3914.
60. William JH, Danziger J (2016). Magnesium Deficiency and Proton-Pump Inhibitor Use: A Clinical Review. J Clin Pharmacol, 56(6): 660-8.
61. Dorup I (1994). Magnesium and potassium deficiency. Its diagnosis, occurrence and treatment in diuretic therapy and its consequences for growth, protein synthesis and growth factors. Acta Physiol Scand Suppl, 618: 1-55.
2. Grober U, Schmidt J, Kisters K (2015). Magnesium in Prevention and Therapy. Nutrients, 7(9): 8199-226.
3. Vink R (2016). Magnesium in the CNS: recent advances and developments. Magnes Res, 29(3): 95-101.
4. Slutsky I, Abumaria N, Wu L J et al (2010). Enhancement of learning and memory by elevating brain magnesium. Neuron, 65(2): 165-77.
5. Libien J, Sacktor T C,Kass I S (2005). Magnesium blocks the loss of protein kinase C, leads to a transient translocation of PKC(alpha) and PKC(epsilon), and improves recovery after anoxia in rat hippocampal slices. Brain Res Mol Brain Res, 136(1-2): 104-11.
6. Mayer M L, Westbrook G L,Guthrie P B (1984). Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones. Nature, 309(5965):261-3.
7. Nowak L, Bregestovski P, Ascher P et al (1984). Magnesium gates glutamate-activated channels in mouse central neurones. Nature, 307(5950):462-5.
8. Gums J G (2004). Magnesium in cardiovascular and other disorders. Am J Health Syst Pharm, 61(15):1569-76.
9. Altura B,Altura B (2016). Importance of ionized magnesium measurements in physiology and medicine and the need for ion-selective electrodes. J Clin Case Stu, 1(2): doi https://www.sciforschenonline.org/journals/clinical-case-studies/JCCS-1-111.php
10. Vormann J, Anke M (2002). Dietary magnesium: supply, requirements and recommendations-results from duplicate and balance studies in man. J Clin Basic Cardiol, 5:49-53.
11. Azoulay A, Garzon P,Eisenberg MJ (2001). Comparison of the mineral content of tap water and bottled waters. J Gen Intern Med, 16(3): 168-75.
12. Murck H (2002). Magnesium and affective disorders. Nutr Neurosci, 5(6): 375-89.
13. Chang JJ, Mack WJ, Saver JL, Sanossian N (2014). Magnesium: potential roles in neurovascular disease. Front Neurol, 5: 52.
14. Jahnen-Dechent W, Ketteler M (2012). Magnesium basics. Clin Kidney J, 5(Suppl 1):i3-i14..
15. Findlay JM, Nisar J, Darsaut T (2016). Cerebral Vasospasm: A Review. Can J Neurol Sci, 43: 15-32.
16. Farago M, Szabo C, Dora E et al (1991). Contractile and endothelium-dependent dilatory responses of cerebral arteries at various extracellular magnesium concentrations. J Cereb Blood Flow Metab, 11(1): 161-4.
17. Hanline M Jr (1985). Hypomagnesemia causes coronary artery spasm. JAMA, 253(3):342.
18. Keith W. Muir (2000). Therapeutic potential of magnesium in the treatment of acute stroke. J Stroke Cerebrovasc Dis, 9(6): 257-67.
19. Longstreth WT Jr, Fahrenbruch CE, Olsufka M et al (2002). Randomized clinical trial of magnesium, diazepam, or both after out-of-hospital cardiac arrest. Neurology, 59(4):506-14.
20. Treggiari-Venzi MM, Suter PM, Romand JA (2001). Review of medical prevention of vasospasm after aneurysmal subarachnoid hemorrhage: a problem of neurointensive care. Neurosurgery, 48(2): 249-62.
21. Westermaier T, Zausinger S, Baethmann A,Schmid-Elsaesser R (2005). Dose finding study of intravenous magnesium sulphate in transient focal cerebral ischemia in rats. Acta Neurochir (Wien), 147(5): 525-32.
22. Stippler M, Crago E, Levy EI et al (2006). Magnesium infusion for vasospasm prophylaxis after subarachnoid hemorrhage. J Neurosurg, 105(5):723-9.
23. Fann DY, Lee SY, Manzanero S et al (2013). Pathogenesis of acute stroke and the role of inflammasomes. Ageing Res Rev, 12(4): 941-66.
24. Adeoye O, Hornung R, Khatri P, Kleindorfer D (2011). Recombinant tissue-type plasminogen activator use for ischemic stroke in the United States: a doubling of treatment rates over the course of 5 years. Stroke, 42(7): 1952-5.
25. Saver J L (2011). Improving reperfusion therapy for acute ischaemic stroke. J Thromb Haemost, 9 Suppl 1:333-43.
26. Muir KW, Lees KR, Ford I et al (2004). Magnesium for acute stroke (Intravenous Magnesium Efficacy in Stroke trial): randomised controlled trial. Lancet, 363(9407): 439-45.
27. Pan W H, Lai Y H, Yeh W T et al (2017). Intake of potassium- and magnesium-enriched salt improves functional outcome after stroke: a randomized, multicenter, double-blind controlled trial. Am J Clin Nutr, 106(5): 1267-73.
28. Ferre S, Mazur A, Maier J A (2007). Low-magnesium induces senescent features in cultured human endothelial cells. Magnes Res, 20(1): 66-71.
29. Wolf F I, Trapani V, Simonacci M et al (2008). Magnesium deficiency and endothelial dysfunction: is oxidative stress involved? Magnes Res, 21(1): 58-64.
30. Larsson SC, Orsini N, Wolk A (2012). Dietary magnesium intake and risk of stroke: a meta-analysis of prospective studies. Am J Clin Nutr, 95(2): 362-6.
31. Volpe SL (2013). Magnesium in disease prevention and overall health. Adv Nutr, 4(3): 378S-83S.
32. Lin JY, Chung SY, Lin M C, Cheng F C (2002). Effects of magnesium sulfate on energy metabolites and glutamate in the cortex during focal cerebral ischemia and reperfusion in the gerbil monitored by a dual-probe microdialysis technique. Life Sci, 71(7): 803-11.
33. Sharp FR, Lu A, Tang Y, Millhorn D E (2000). Multiple molecular penumbras after focal cerebral ischemia. J Cereb Blood Flow Metab, 20(7): 1011-32.
34. Heiss W D, Thiel A, Grond M,Graf R (1999). Which targets are relevant for therapy of acute ischemic stroke? Stroke, 30(7):1486-9.
35. Lipton P (1999). Ischemic cell death in brain neurons. Physiol Rev, 79(4): 1431-568.
36. Mori K, Yamamoto T, Nakao Y et al (2009). Initial clinical experience of vasodilatory effect of intra-cisternal infusion of magnesium sulfate for the treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Neurol Med Chir (Tokyo), 49(4): 139-45.
37. Adebamowo S N, Spiegelman D, Willett W C, Rexrode K M (2015). Association between intakes of magnesium, potassium, and calcium and risk of stroke: 2 cohorts of US women and updated meta-analyses. Am J Clin Nutr, 101(6): 1269-77.
38. Grundke-Iqbal I, Iqbal K, Tung YC et al (1986). Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci U S A, 83(13): 4913-7.
39. Gandy S,Greengard P (1992). Amyloidogenesis in Alzheimer's disease: some possible therapeutic opportunities. Trends Pharmacol Sci, 13(3):108-13.
40. LaFerla F M,Oddo S (2005). Alzheimer's disease: Abeta, tau and synaptic dysfunction. Trends Mol Med, 11(4):170-6.
41. Prince M, Bryce R, Albanese E et al (2013). The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement, 9(1):63-75.e2.
42. Fan X, Wheatley EG,Villeda SA (2017). Mechanisms of Hippocampal Aging and the Potential for Rejuvenation. Annu Rev Neurosci, 40: 251-72.
43. Durlach J (1990). Magnesium depletion and pathogenesis of Alzheimer's disease. Magnes Res, 3(3): 217-8.
44. Barbagallo M, Belvedere M, Di Bella G et al (2011). Altered ionized magnesium levels in mild-to-moderate Alzheimer's disease. Magnes Res, 24(3): S115-21.
45. Xu Z P, Li L, Bao J et al (2014). Magnesium protects cognitive functions and synaptic plasticity in streptozotocin-induced sporadic Alzheimer's model. PLoS One, 9(9):e108645.
46. Hampel H, Mitchell A, Blennow K et al (2004). Core biological marker candidates of Alzheimer's disease - perspectives for diagnosis, prediction of outcome and reflection of biological activity. J Neural Transm (Vienna), 111(3): 247-72.
47. Sherer T B, Betarbet R, Testa C M et al (2003). Mechanism of toxicity in rotenone models of Parkinson's disease. J Neurosci, 23(34): 10756-64.
48. Conway KA, Lee SJ, Rochet JC et al (2000). Acceleration of oligomerization, not fibrillization, is a shared property of both alpha-synuclein mutations linked to early-onset Parkinson's disease: implications for pathogenesis and therapy. Proc Natl Acad Sci U S A, 97(2): 571-6.
49. Golts N, Snyder H, Frasier M et al (2002). Magnesium inhibits spontaneous and iron-induced aggregation of alpha-synuclein. J Biol Chem, 277(18):16116-23.
50. Yasui M, Kihira T,Ota K (1992). Calcium, magnesium and aluminum concentrations in Parkinson's disease. Neurotoxicology, 13(3): 593-600.
51. Forte G, Alimonti A, Violante N et al (2005). Calcium, copper, iron, magnesium, silicon and zinc content of hair in Parkinson's disease. J Trace Elem Med Biol, 19(2-3): 195-201.
52. Silberstein SD (2004). Migraine. Lancet, 363(9406):381-91.
53. Olesen J, Steiner T J (2004). The International classification of headache disorders, 2nd edn (ICDH-II). J Neurol Neurosurg Psychiatry, 75(6): 808-11.
54. Clifford Rose F (1991). The pathogenesis of migraine. J R Soc Med, 84(9):519-21.
55. Daniel O, Mauskop A (2016). Nutraceuticals in Acute and Prophylactic Treatment of Migraine. Curr Treat Options Neurol, 18(4):14.
56. Talebi M, Savadi-Oskouei D, Farhoudi M et al (2011). Relation between serum magnesium level and migraine attacks. Neurosciences (Riyadh), 16(4): 320-3.
57. Demirkaya S, Vural O, Dora B, Topcuoglu MA (2001). Efficacy of intravenous magnesium sulfate in the treatment of acute migraine attacks. Headache, 41(2): 171-7.
58. Trauninger A, Pfund Z, Koszegi T, Czopf J (2002). Oral magnesium load test in patients with migraine. Headache, 42(2): 114-9.
59. Schurks M, Rist PM, Bigal ME et al (2009). Migraine and cardiovascular disease: systematic review and meta-analysis. BMJ, 339: b3914.
60. William JH, Danziger J (2016). Magnesium Deficiency and Proton-Pump Inhibitor Use: A Clinical Review. J Clin Pharmacol, 56(6): 660-8.
61. Dorup I (1994). Magnesium and potassium deficiency. Its diagnosis, occurrence and treatment in diuretic therapy and its consequences for growth, protein synthesis and growth factors. Acta Physiol Scand Suppl, 618: 1-55.
| Files | ||
| Issue | Vol 48 No 3 (2019) | |
| Section | Review Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v48i3.880 | |
| Keywords | ||
| Magnesium Neurological disorders Alzheimer’s disease Parkinson’s disease Stroke Migraine | ||
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How to Cite
1.
XUE W, YOU J, SU Y, WANG Q. The Effect of Magnesium Deficiency on Neurological Disorders: A Narrative Review Article. Iran J Public Health. 2019;48(3):379-387.
