Magnesium: The Neglected Electrolyte? A Clinical Review


Magnesium, Mg2+, is the second most abundant intracellular cation after potassium and the fourth most abundant in the body. It was first isolated in 1808 by the English chemist, Sir Humphrey Davy. Magnesium is essential to numerous biochemical reactions. It modulates key physiological processes such as metabolic biochemistry, nucleic acid synthesis, receptor-binding and ion flux. The western diet falls short of the recommended daily allowance of 4.5 mg/Kg/day and important dietary sources are seeds, grains, nuts and green vegetables. It is used as a therapeutic agent in a broad range of pathologies: neurological, cardiovascular, respiratory, gastrointestinal and obstetric. The pharmacokinetics and pharmacodynamics of magnesium, as a drug, are not well understood. Despite its fundamental importance to human physiology, it remains an electrolyte that is not routinely measured as part of the “urea & electrolytes” test and is the most overlooked electrolyte deficiency in hospital inpatients. This review will summarise the importance of magnesium homeostasis, its pharmacological effects and clinical applications.

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Sharma, P. , Chung, C. and Vizcaychipi, M. (2014) Magnesium: The Neglected Electrolyte? A Clinical Review. Pharmacology & Pharmacy, 5, 762-772. doi: 10.4236/pp.2014.57086.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Saris, N.E., Mervaala, E., Karppanen, H., Khawaja, J.A. and Lewenstam, A. (2000) Magnesium: An Update on Physiological, Clinical and Analytical Aspects. Clinica Chimica Acta, 294, 1-26.
[2] Swaminathan, R. (2003) Magnesium Metabolism and Its Disorders. The Clinical Biochemist Reviews, 24, 47-66.
[3] Elin, R.J. (2010) Assessment of Magnesium Status for Diagnosis and Therapy. Magnesium Research, 23, S194-S198.
[4] Dollery, C. (1998) Therapeutic Drugs. 2nd Edition, Churchill Livingstone, London.
[5] Kayne, L.H. and Lee, D.B. (1993) Intestinal Magnesium Absorption. Mineral and Electrolyte Metabolism, 19, 210-217.
[6] Beyenbach, K.W. (1990) Transport of Magnesium across Biological Membranes. Magnesium and Trace Elements, 9, 233-254.
[7] Quamme, G.A. (1997) Renal Magnesium Handling: New Insights in Understanding Old Problems. Kidney International, 52, 1180-1195.
[8] Bailly, C., Roinel, N. and Amiel, C. (1985) Stimulation by Glucagon and PTH of Ca and Mg Reabsorption in the Superficial Distal Tubule of the Rat Kidney. Pflügers Archiv, 403, 28-34.
[9] Zofkova, I. and Kancheva, R.L. (1995) The Relationship between Magnesium and Calciotropic Hormones. Magnesium Research, 8, 77-84.
[10] Paolisso, G. and Barbagallo, M. (1997) Hypertension, Diabetes Mellitus, and Insulin Resistance: The Role of Intracellular Magnesium. American Journal of Hypertension, 10, 346-355.
[11] Hwang, D.L., Yen, C.F. and Nadler, J.L. (1993) Insulin Increases Intracellular Magnesium Transport in Human Platelets. Journal of Clinical Endocrinology & Metabolism, 76, 549-553.
[12] Corica, F., Allegra, A., Ientile, R., Buemi, M., Corsonello, A., Bonanzinga, S., et al. (1999) Changes in Plasma, Erythrocyte, and Platelet Magnesium Levels in Normotensive and Hypertensive Obese Subjects during Oral Glucose Tolerance Test. American Journal of Hypertension, 12, 128-136.
[13] Jacomella, V., Sauser, A., Truttmann, A.C., Kuhlmann-Siegenthaler, B.V., Capillo, S. and Bianchetti, M.G. (1997) Free Plasma Magnesium Following Glucose Loading in Healthy Humans. Acta Diabetologica, 34, 235-237.
[14] Bailly, C., Roinel, N. and Amiel, C. (1985) Stimulation by Glucagon and PTH of Ca and Mg Reabsorption in the Superficial Distal Tubule of the Rat Kidney. Pflugers Archiv, 403, 28-34.
[15] Rossier, M.C., Truttmann, A.C., von Vigier, R.O., Stoffel, P.B. and Bianchetti, M.G. (1999) Free and Total Circulating Magnesium Following Glucagon Injection in Humans. Magnesium Research, 12, 175-179.
[16] Altura, B.M. (1994) Introduction: Importance of Mg in Physiology and Medicine and the Need for Ion Selective Electrodes. Scandinavian Journal of Clinical and Laboratory Investigation Supplementum, 217, 5-9.
[17] Cowan, J.A. (2002) Structural and Catalytic Chemistry of Magnesium-Dependent Enzymes. Biometals, 15, 225-235.
[18] Hwang, D.L., Yen, C.F. and Nadler, J.L. (1992) Effect of Extracellular Magnesium on Platelet Activation and Intracellular Calcium Mobilization. American Journal of Hypertension, 5, 700-706.
[19] Gawaz, M., Ott, I., Reininger, A.J. and Neumann, F.J. (1994) Effects of Magnesium on Platelet Aggregation and Adhesion. Magnesium Modulates Surface Expression of Glycoproteins on Platelets in Vitro and ex Vivo. Thrombosis and Haemostasis, 72, 912-918.
[20] Ravn, H.B., Vissinger, H., Kristensen, S.D., Wennmalm, A., Thygesen, K. and Husted, S.E. (1996) Magnesium Inhibits Platelet Activity—An Infusion Study in Healthy Volunteers. Thrombosis and Haemostasis, 75, 939-944.
[21] Sekiya, F., Yoshida, M., Yamashita, T. and Morita, T. (1996) Magnesium(II) Is a Crucial Constituent of the Blood Coagulation Cascade. Potentiation of Coagulant Activities of Factor IX by Mg2+ Ions. Journal of Biological Chemistry, 271, 8541-8544.
[22] Ravn, H.B., Lassen, J.F., Bergenhem, N. and Kristensen, A.T. (2001) Intravenous Magnesium Does Not Influence the Activity of the Coagulation Cascade. Blood Coagulation & Fibrinolysis, 12, 223-228.
[23] Ames, W.A., McDonnell, N. and Potter, D. (1999) The Effect of Ionised Magnesium on Coagulation Using Thromboelastography. Anaesthesia, 54, 999-1001.
[24] Harnett, M.J., Datta, S. and Bhavani-Shankar, K. (2001) The Effect of Magnesium on Coagulation in Parturients with Preeclampsia. Anesthesia & Analgesia, 92, 1257-1260.
[25] Katritch, V., Cherezov, V. and Stevens, R.C. (2013) Structure-Function of the G Protein-Coupled Receptor Superfamily. Annual Review of Pharmacology and Toxicology, 53, 531-556.
[26] Birnbaumer, L. and Zurita, A.R. (2010) On the Roles of Mg in the Activation of G Proteins. Journal of Receptors and Signal Transduction, 30, 372-375.
[27] Laver, D.R., Baynes, T.M. and Dulhunty, A.F. (1997) Magnesium Inhibition of Ryanodine-Receptor Calcium Channels: Evidence for Two Independent Mechanisms. The Journal of Membrane Biology, 156, 213-229.
[28] Gusev, K. and Niggli, E. (2008) Modulation of the Local SR Ca2+ Release by Intracellular Mg2+ in Cardiac Myocytes. Journal of General Physiology, 132, 721-730.
[29] Stephenson, E.W. and Podolsky, R.J. (1977) Regulation by Magnesium of Intracellular Calcium Movement in Skinned Muscle Fibers. Journal of General Physiology, 69, 1-16.
[30] Podolsky, R.J. and Costantin, L.L. (1964) Regulation by Calcium of the Contraction and Relaxation of Muscle Fibers. Federation Proceedings, 23, 933-939.
[31] Iseri, L.T. and French, J.H. (1984) Magnesium: Nature’s Physiologic Calcium Blocker. American Heart Journal, 108, 188-193.
[32] Kiedrowski, L., Brooker, G., Costa, E. and Wroblewski, J.T. (1994) Glutamate Impairs Neuronal Calcium Extrusion While Reducing Sodium Gradient. Neuron, 12, 295-300.
[33] Ledvora, R.F. and Hegyvary, C. (1983) Dependence of Na+-Ca2+ Exchange and Ca2+-Ca2+ Exchange on Monovalent Cations. Biochimica et Biophysica Acta (BBA), Biomembranes, 729, 123-136.
[34] Smith, J.B., Cragoe, E.J. and Smith Jr., L. (1987) Na+/Ca2+ Antiport in Cultured Arterial Smooth Muscle Cells. Inhibition by Magnesium and Other Divalent Cations. Journal of Biological Chemistry, 262, 11988-11994.
[35] Bara, M., Guiet-Bara, A. and Durlach, J. (1993) Regulation of Sodium and Potassium Pathways by Magnesium in Cell Membranes. Magnesium Research, 6, 167-177.
[36] Pusch, M. (1990) Open-Channel Block of Na+ Channels by Intracellular Mg2+. European Biophysics Journal, 18, 317-326.
[37] Matsuda, H., Saigusa, A. and Irisawa, H. (1987) Ohmic Conductance through the Inwardly Rectifying K Channel and Blocking by Internal Mg2+. Nature, 325, 156-159.
[38] Horie, M. and Irisawa, H. (1989) Dual Effects of Intracellular Magnesium on Muscarinic Potassium Channel Current in Single Guinea-Pig Atrial Cells. Journal of Physiology, 408, 313-332.
[39] Noma, A. (1983) ATP-Regulated K+ Channels in Cardiac Muscle. Nature, 305, 147-148.
[40] Ashcroft, F.M. (1988) Adenosine 5’-Triphosphate-Sensitive Potassium Channels. Annual Review of Neuroscience, 11, 97-118.
[41] Ashcroft, F.M. and Kakei, M. (1989) ATP-Sensitive K+ Channels in Rat Pancreatic Beta-Cells: Modulation by ATP and Mg2+ Ions. Journal of Physiology, 416, 349-367.
[42] Horie, M, Irisawa, H. and Noma, A. (1987) Voltage-Dependent Magnesium Block of Adenosine-Triphosphate-Sensitive Potassium Channel in Guinea-Pig Ventricular Cells. Journal of Physiology, 387, 251-272.
[43] Noma, A. and Shibasaki, T. (1985) Membrane Current through Adenosine-Triphosphate-Regulated Potassium Channels in Guinea-Pig Ventricular Cells. Journal of Physiology, 363, 463-480.
[44] Chuan, F.S., Charles, B.G., Boyle, R.K. and Rasiah, R.L. (2001) Population Pharmacokinetics of Magnesium in Preeclampsia. American Journal of Obstetrics & Gynecology, 185, 593-599.
[45] Lu, J., Pfister, M., Ferrari, P., Chen, G. and Sheiner, L. (2002) Pharmacokinetic-Pharmacodynamic Modelling of Magnesium Plasma Concentration and Blood Pressure in Preeclamptic Women. Clinical Pharmacokinetics, 41, 1105-1113.
[46] De Oliveira Jr., G.S., Castro-Alves, L.J., Khan, J.H. and McCarthy, R.J. (2013) Perioperative Systemic Magnesium to Minimize Postoperative Pain: A Meta-Analysis of Randomized Controlled Trials. Anesthesiology, 119, 178-190.
[47] Tramer, M.R., Schneider, J., Marti, R.A. and Rifat, K. (1996) Role of Magnesium Sulfate in Postoperative Analgesia. Anesthesiology, 84, 340-347.
[48] Yousef, A.A. and Al-Deeb, A.E. (2013) A Double-Blinded Randomised Controlled Study of the Value of Sequential Intravenous and Oral Magnesium Therapy in Patients with Chronic Low Back Pain with a Neuropathic Component. Anaesthesia, 68, 260-266.
[49] Rondanelli, M., Opizzi, A., Monteferrario, F., Antoniello, N., Manni, R. and Klersy, C. (2011) The Effect of Melatonin, Magnesium, and Zinc on Primary Insomnia in Long-Term Care Facility Residents in Italy: A Double-Blind, Placebo-Controlled Clinical Trial. Journal of the American Geriatrics Society, 59, 82-90.
[50] Fawcett, W.J., Haxby, E.J. and Male, D.A. (1999) Magnesium: Physiology and Pharmacology. British Journal of Anaesthesia, 83, 302-320.
[51] Moran, J.L., Gallagher, J., Peake, S.L., Cunningham, D.N., Salagaras, M. and Leppard, P. (1995) Parenteral Magnesium Sulfate versus Amiodarone in the Therapy of Atrial Tachyarrhythmias: A Prospective, Randomized Study. Critical Care Medicine, 23, 1816-1824.
[52] Brookes, C.I. and Fry, C.H. (1993) Ionised Magnesium and Calcium in Plasma from Healthy Volunteers and Patients Undergoing Cardiopulmonary Bypass. British Heart Journal, 69, 404-408.
[53] Miller, S., Crystal, E., Garfinkle, M., Lau, C., Lashevsky, I. and Connolly, S.J. (2005) Effects of Magnesium on Atrial Fibrillation after Cardiac Surgery: A Meta-Analysis. Heart, 91, 618-623.
[54] Shiga, T., Wajima, Z., Inoue, T. and Ogawa, R. (2004) Magnesium Prophylaxis for Arrhythmias after Cardiac Surgery: A Meta-Analysis of Randomized Controlled Trials. The American Journal of Medicine, 117, 325-333.
[55] Hearse, D.J., Stewart, D.A. and Braimbridge, M.V. (1978) Myocardial Protection during Ischemic Cardiac Arrest. The Importance of Magnesium in Cardioplegic Infusates. Journal of Thoracic and Cardiovascular Surgery, 75, 877-885.
[56] Shakerinia, T., Ali, I.M. and Sullivan, J.A. (1996) Magnesium in Cardioplegia: Is It Necessary? Canadian Journal of Surgery, 39, 397-400.
[57] Douglas, W.W. and Rubin, R.P. (1963) The Mechanism of Catecholamine Release from the Adrenal Medulla and the Role of Calcium in Stimulus-Secretion Coupling. Journal of Physiology, 167, 288-310.
[58] Rubin, R.P., Feinstein, M.B., Jaanus, S.D. and Paimre, M. (1967) Inhibition of Catecholamine Secretion and Calcium Exchange in Perfused Cat Adrenal Glands by Tetracaine and Magnesium. Journal of Pharmacology and Experimental Therapeutics, 155, 463-471.
[59] James, M.F. (1989) Use of Magnesium Sulphate in the Anaesthetic Management of Phaeochromocytoma: A Review of 17 Anaesthetics. British Journal of Anaesthesia, 62, 616-623.
[60] British Thoracic Society (2012) Scottish Intercollegiate Guidelines Network. British Guideline on the Management of Asthma, 117.
[61] Rowe, B.H., Bretzlaff, J.A., Bourdon, C., Bota, G.W. and Camargo Jr., C.A. (2000) Magnesium Sulfate for Treating Exacerbations of Acute Asthma in the Emergency Department. Cochrane Database of Systematic Reviews, Article ID: CD001490.
[62] Dhingra, S., Solven, F., Wilson, A. and McCarthy, D.S. (1984) Hypomagnesemia and Respiratory Muscle Power. American Review of Respiratory Disease, 129, 497-498.
[63] Mendelson, C.L. (1946) The Aspiration of Stomach Contents into the Lungs during Obstetric Anesthesia. American Journal of Obstetrics & Gynecology, 52, 191-205.
[64] Berris, B. and Kasler, D. (1965) Pulmonary Aspiration of Gastric Acid—Mendelson’s Syndrome. Canadian Medical Association Journal, 92, 905-907.
[65] Husemeyer, R.P., Davenport, H.T. and Rajasekaran, T. (1978) Cimetidine as a Single Oral Dose for Prophylaxis against Mendelson’s Syndrome. Anaesthesia, 33, 775-778.
[66] Husemeyer, R.P. and Davenport, H.T. (1980) Prophylaxis for Mendelson’s Syndrome before Elective Caesarean Section. A Comparison of Cimetidine and Magnesium Trisilicate Mixture Regimens. BJOG: An International Journal of Obstetrics & Gynaecology, 87, 565-570.
[67] Duley, L., Henderson-Smart, D.J., Walker, G.J. and Chou, D. (2010) Magnesium Sulphate versus Diazepam for Eclampsia. Cochrane Database of Systematic Reviews, Article ID: CD000127.
[68] Duley, L., Gulmezoglu, A.M., Henderson-Smart, D.J. and Chou, D. (2010) Magnesium Sulphate and Other Anticonvulsants for Women with Pre-Eclampsia. Cochrane Database of Systematic Reviews, Article ID: CD000025.
[69] Altman, D., Carroli, G., Duley, L., Farrell, B., Moodley, J., Neilson, J., et al. (2002) Do Women with Pre-Eclampsia, and Their Babies, Benefit from Magnesium Sulphate? The Magpie Trial: A Randomised Placebo-Controlled Trial. The Lancet, 359, 1877-1890.
[70] Bringhurst, F.R., Demay, M.B., Krane, S.M. and Kronenberg, H.M. (2005) Bone and Mineral Metabolism in Health and Disease. In: Kasper, D.L., Braunwald, E., Hauser, S., Longo, D., Jameson, J.L. and Fauci, A.S., Eds., Harrison’s Principles of Internal Medicine, 16th Edition, McGraw-Hill, New York.
[71] Whang, R., Hampton, E.M. and Whang, D.D. (1994) Magnesium Homeostasis and Clinical Disorders of Magnesium Deficiency. Annals of Pharmacotherapy, 28, 220-226.
[72] Slutsky, I., Abumaria, N., Wu, L.J., Huang, C., Zhang, L., Li, B., et al. (2010) Enhancement of Learning and Memory by Elevating Brain Magnesium. Neuron, 65, 165-177.
[73] Sinatra, R.S., Philip, B.K., Naulty, J.S. and Ostheimer, G.W. (1985) Prolonged Neuromuscular Blockade with Vecuronium in a Patient Treated with Magnesium Sulfate. Anesthesia & Analgesia, 64, 1220-1222.
[74] Fuchs-Buder, T., Wilder-Smith, O.H., Borgeat, A. and Tassonyi, E. (1995) Interaction of Magnesium Sulphate with Vecuronium-Induced Neuromuscular Block. British Journal of Anaesthesia, 74, 405-409.
[75] Fuchs-Buder, T. and Tassonyi, E. (1996) Magnesium Sulphate Enhances Residual Neuromuscular Block Induced by Vecuronium. British Journal of Anaesthesia, 76, 565-566.
[76] Pinard, A.M., Donati, F., Martineau, R., Denault, A.Y., Taillefer, J. and Carrier, M. (2003) Magnesium Potentiates Neuromuscular Blockade with Cisatracurium during Cardiac Surgery. Canadian Journal of Anaesthesia, 50, 172-178.
[77] James, M.F., Cork, R.C. and Dennett, J.E. (1986) Succinylcholine Pretreatment with Magnesium Sulfate. Anesthesia & Analgesia, 65, 373-376.
[78] Wadhwa, A., Sengupta, P., Durrani, J., Akca, O., Lenhardt, R., Sessler, D.I., et al. (2005) Magnesium Sulphate Only Slightly Reduces the Shivering Threshold in Humans. British Journal of Anaesthesia, 94, 756-762.
[79] Beliaev, A.V., Ryzhin, S.M. and Dubov, A.M. (1991) Use of Magnesium Sulfate for Controlling Postoperative Shivering. KlinKhir, 3, 42-44.
[80] Miyakawa, H., Matsumoto, K., Matsumoto, S., Mori, M., Yoshitake, S., Noguchi, T., et al. (1991) A Comparison of Three Drugs (Pethidine, Magnesium Sulfate and Droperidol) in Patients with Post-Anesthesia Shivering. Masui, 40, 1503-1506.
[81] Kizilirmak, S., Karakas, S.E., Akca, O., Ozkan, T., Yavru, A., Pembeci, K., et al. (1997) Magnesium Sulfate Stops Postanesthetic Shivering. Annals of the New York Academy of Sciences, 813, 799-806.
[82] Kranke, P., Eberhart, L.H., Roewer, N. and Tramer, M.R. (2002) Pharmacological Treatment of Postoperative Shivering: A Quantitative Systematic Review of Randomized Controlled Trials. Anesthesia & Analgesia, 94, 453-460.
[83] Christensen, C.W., Rieder, M.A., Silverstein, E.L. and Gencheff, N.E. (1995) Magnesium Sulfate Reduces Myocardial Infarct Size When Administered before but Not after Coronary Reperfusion in a Canine Model. Circulation, 92, 2617-2621.
[84] Woods, K.L., Fletcher, S., Roffe, C. and Haider, Y. (1992) Intravenous Magnesium Sulphate in Suspected Acute Myocardial Infarction: Results of the Second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2). The Lancet, 339, 1553-1558.
[85] ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group (1995) A Randomised Factorial Trial Assessing Early Oral Captopril, Oral Mononitrate, and Intravenous Magnesium Sulphate in 58,050 Patients with Suspected Acute Myocardial Infarction. The Lancet, 345, 669-685.
[86] Magnesium in Coronaries (MAGIC) Trial Investigators (2002) Early Administration of Intravenous Magnesium to High-Risk Patients with Acute Myocardial Infarction in the Magnesium in Coronaries (MAGIC) Trial: A Randomised Controlled Trial. The Lancet, 360, 1189-1196.

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