Magnesium is an ubiquitous element and its formulation determines its efficacy and administration. It is used for gastrointestinal and obstetric disease and recently cardiovascular and neurological indications have also been explored. The role of serum/dietary magnesium intake on cardiovascular disease, carotid intima-media thickness (CIMT), hypertension (HTN) and cholesterol synthesis has been investigated. Despite differences in patient populations, some observational and interventional studies have suggested that low serum/dietary magnesium is associated with higher CIMT and more cardiovascular risk factors. A few clinical and basic science interventional studies have also shown the benefits of magnesium administration in cardiovascular disease prevention and as a neuroprotective agent. Low magnesium levels have been implicated in inflammation and endothelial dysfunction. Hypomagnesemia results in increased C-reactive protein and cytokine exaggeration, increased nuclear factor kappa B and platelet dysfunction, which can lead to thrombosis. Magnesium appears to play a vital function in cardiovascular stability and health, but an optimal dose and formulation has not been defined. Potentially promising avenues include the combination of magnesium with a statin to reduce cholesterol, C-reactive protein and CIMT, and its early use to reduce stroke morbidity and mortality. Understanding the role of magnesium in inflammation and mineralization and how it has the potential for playing a role in modulating cardiovascular and neurological disease can be a new frontier in medicine.

1.
Fawcett WJ, Haxby EJ, Male DA: Magnesium: physiology and pharmacology. Br J Anaesth 1999;83:302–320.
2.
Arnaud MJ: Update on the assessment of magnesium status. Br J Nutr 2008;99(suppl 3):S24–S36.
3.
Simsek E, Karabay M, Kocabay K: Assessment of magnesium status in newly diagnosed diabetic children: measurement of erythrocyte magnesium level and magnesium tolerance testing. Turk J Pediatr 2005;47:132–137.
4.
Malon A, Brockmann C, Fijalkowska-Morawska J, Rob P, Maj-Zurawska M: Ionized magnesium in erythrocytes – the best magnesium parameter to observe hypo- or hypermagnesemia. Clin Chim Acta 2004;349:67–73.
5.
Emelyanov A, Fedoseev G, Barnes PJ: Reduced intracellular magnesium concentrations in asthmatic patients. Eur Respir J 1999;13:38–40.
6.
Andrade CS, Otaduy MC, Valente KD, Maia DF, Park EJ, Valerio RM, Tsunemi MH, Leite CC: Phosphorus magnetic resonance spectroscopy in malformations of cortical development. Epilepsia 2011;52:2276–2284.
7.
Moe SM: Disorders involving calcium, phosphorus, and magnesium. Prim Care 2008;35:215–237.
8.
Ranade VV, Somberg JC: Bioavailability and pharmacokinetics of magnesium after administration of magnesium salts to humans. Am J Ther 2001;8:345–357.
9.
Schuette SA, Lashner BA, Janghorbani M: Bioavailability of magnesium diglycinate vs magnesium oxide in patients with ileal resection. J Parenter Enteral Nutr 1994;18:430–435.
10.
Coudray C, Rambeau M, Feillet-Coudray C, Gueux E, Tressol JC, Mazur A, Rayssiguier Y: Study of magnesium bioavailability from ten organic and inorganic Mg salts in Mg-depleted rats using a stable isotope approach. Magnes Res 2005;18:215–223.
11.
Mazur A, Maier JA, Rock E, Gueux E, Nowacki W, Rayssiguier Y: Magnesium and the inflammatory response: potential physiopathological implications. Arch Biochem Biophys 2007;458:48–56.
12.
Bo S, Pisu E: Role of dietary magnesium in cardiovascular disease prevention, insulin sensitivity and diabetes. Curr Opin Lipidol 2008;19:50–56.
13.
Houston M: The role of magnesium in hypertension and cardiovascular disease. J Clin Hypertens (Greenwich) 2011;13:843–847.
14.
Rayssiguier Y: Magnesium, lipids and vascular diseases. Experimental evidence in animal models. Magnesium 1986;5:182–190.
15.
Rosanoff A, Seelig MS: Comparison of mechanism and functional effects of magnesium and statin pharmaceuticals. J Am Coll Nutr 2004;23:501S–505S.
16.
Reinhart K, Baker WL, Siv ML: Beyond the guidelines: new and novel agents for the prevention of atrial fibrillation after cardiothoracic surgery. J Cardiovasc Pharmacol Ther 2011;16:5–13.
17.
Kawano Y, Matsuoka H, Takishita S, Omae T: Effects of magnesium supplementation in hypertensive patients: assessment by office, home, and ambulatory blood pressures. Hypertension 1998;32:260–265.
18.
Standing Committee on the Scientific Evaluation of Dietary Reference Intakes FaNB, Institute of Medicine Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D and Fluoride. Washington, National Academy Press, 1997.
19.
Rosanoff A: Magnesium supplements may enhance the effect of antihypertensive medications in stage 1 hypertensive subjects. Magnes Res 2010;23:27–40.
20.
Song Y, Sesso HD, Manson JE, Cook NR, Buring JE, Liu S: Dietary magnesium intake and risk of incident hypertension among middle-aged and older US women in a 10-year follow-up study. Am J Cardiol 2006;98:1616–1621.
21.
Ma Y, Hebert JR, Li W, Bertone-Johnson ER, Olendzki B, Pagoto SL, Tinker L, Rosal MC, Ockene IS, Ockene JK, Griffith JA, Liu S: Association between dietary fiber and markers of systemic inflammation in the Women’s Health Initiative observational study. Nutrition 2008;24:941–949.
22.
Galland L: Diet and inflammation. Nutr Clin Pract 2010;25:634–640.
23.
Altura BT, Brust M, Bloom S, Barbour RL, Stempak JG, Altura BM: Magnesium dietary intake modulates blood lipid levels and atherogenesis. Proc Natl Acad Sci USA 1990;87:1840–1844.
24.
Maier JA: Endothelial cells and magnesium: implications in atherosclerosis. Clin Sci (Lond) 2012;122:397–407.
25.
Salem S, Bruck H, Bahlmann FH, Peter M, Passlick-Deetjen J, Kretschmer A, Steppan S, Volsek M, Kribben A, Nierhaus M, Jankowski V, Zidek W, Jankowski J: Relationship between magnesium and clinical biomarkers on inhibition of vascular calcification. Am J Nephrol 2012;35:31–39.
26.
Sage A, Tintut Y, Garfinkel A, Demer L: Systems biology of vascular calcification. Trends Cardiovasc Med 2009;19:118–123.
27.
Luft FC: Vascular calcification and magnesium. J Mol Med (Berl) 2010;88:437–439.
28.
Li Q, Larusso J, Grand-Pierre AE, Uitto J: Magnesium carbonate-containing phosphate binder prevents connective tissue mineralization in Abcc6(–/–) mice-potential for treatment of pseudoxanthoma elasticum. Clin Transl Sci 2009;2:398–404.
29.
Kupetsky-Rincon EA, Li Q, Uitto J: Magnesium reduces carotid intima-media thickness in a mouse model of pseudoxanthoma elasticum: a novel treatment biomarker. Clin Transl Sci 2012;5:259–264.
30.
Kobolos G AH, Prohaszka Z, Tordai A, Varadi A, Aranyl T: The R1141X loss-of-function mutation of the ABCC6 gene is a strong genetic risk factor for coronary artery disease. Genet Test Mol Biomarkers 2010;14:75–78.
31.
Germain DP, Boutouyrie P, Laloux B, Laurent S: Arterial remodeling and stiffness in patients with pseudoxanthoma elasticum. Arterioscler Thromb Vasc Biol 2003;23:836–841.
32.
Turgut F, Kanbay M, Metin MR, Uz E, Akcay A, Covic A: Magnesium supplementation helps to improve carotid intima-media thickness in patients on hemodialysis. Int Urol Nephrol 2008;40:1075–1082.
33.
Ma J, Folsom AR, Melnick SL, Eckfeldt JH, Sharrett AR, Nabulsi AA, Hutchinson RG, Metcalf PA: Associations of serum and dietary magnesium with cardiovascular disease, hypertension, diabetes, insulin, and carotid arterial wall thickness: the ARIC study. J Clin Epidemiol 1995;48:927–940.
34.
Walker MD, Fleischer J, Rundek T, McMahon DJ, Homma S, Sacco R, Silverberg SJ: Carotid vascular abnormalities in primary hyperparathyroidism. J Clin Endocrinol Metab 2009;94:3849–3856.
35.
Polak JF, Pencina MJ, O’Leary DH, D’Agostino RB: Common carotid artery intima-media thickness progression as a predictor of stroke in multi-ethnic study of atherosclerosis. Stroke 2011;42:3017–3021.
36.
Simon A, Megnien JL, Chironi G: The value of carotid intima-media thickness for predicting cardiovascular risk. Arterioscler Thromb Vasc Biol 2010;30:182–185.
37.
O’Leary DH, Bots ML: Imaging of atherosclerosis: carotid intima-media thickness. Eur Heart J 2010;31:1682–1689.
38.
Yamagishi T, Kato M, Koiwa Y, Omata K, Hasegawa H, Kanai H: Evaluation of plaque stabilization by fluvastatin with carotid intima-medial elasticity measured by a transcutaneous ultrasonic-based tissue characterization system. J Atheroscler Thromb 2009;16:662–673.
39.
Liao F, Folsom AR, Brancati FL: Is low magnesium concentration a risk factor for coronary heart disease? The Atherosclerosis Risk in Communities (ARIC) study. Am Heart J 1998;136:480–490.
40.
Larsson SC, Orsini N, Wolk A: Dietary magnesium intake and risk of stroke: a meta-analysis of prospective studies. Am J Clin Nutr 2012;95:362–366.
41.
Marinov MB, Harbaugh KS, Hoopes PJ, Pikus HJ, Harbaugh RE: Neuroprotective effects of preischemia intra-arterial magnesium sulfate in reversible focal cerebral ischemia. J Neurosurg 1996;85:117–124.
42.
Saver JL: Targeting the brain: Neuroprotection and neurorestoration in ischemic stroke. Pharmacotherapy 2010;30:62S–69S.
43.
Izumi Y, Roussel S, Pinard E, Seylaz J: Reduction of infarct volume by magnesium after middle cerebral artery occlusion in rats. J Cereb Blood Flow Metab 1991;11:1025–1030.
44.
Kass IS, Cottrell JE, Chambers G: Magnesium and cobalt, not nimodipine, protect neurons against anoxic damage in the rat hippocampal slice. Anesthesiology 1988;69:710–715.
45.
McIntosh TK, Vink R, Yamakami I, Faden AI: Magnesium protects against neurological deficit after brain injury. Brain Res 1989;482:252–260.
46.
Muir KW, Lees KR, Ford I, Davis S: Magnesium for acute stroke (intravenous magnesium efficacy in stroke trial): randomised controlled trial. Lancet 2004;363:439–445.
47.
Saver JL, Kidwell C, Eckstein M, Starkman S: Prehospital neuroprotective therapy for acute stroke: results of the field administration of stroke therapy-magnesium (FAST-MAG) pilot trial. Stroke 2004;35:e106–108.
48.
Abbott RD, Ando F, Masaki KH, Tung KH, Rodriguez BL, Petrovitch H, Yano K, Curb JD: Dietary magnesium intake and the future risk of coronary heart disease (the Honolulu Heart Program). Am J Cardiol 2003;92:665–669.
49.
Peters SA, den Ruijter HM, Bots ML: Attenuation of rate of change in carotid intima-media thickness by lipid-modifying drugs: impact on clinical outcomes. Am J Cardiovasc Drugs 2011;11:253–263.
50.
Sivapalaratnam S, van Loendersloot LL, Hutten BA, Kastelein JJ, Trip MD, de Groot E: Long-term LDL-C lowering in heterozygous familial hypercholesterolemia normalizes carotid intima-media thickness. Atherosclerosis 2010;212:571–574.
51.
Riccioni G, Vitulano N, Mancini B, Zanasi A, D’Orazio N: One-year treatment with rosuvastatin reduces intima-media thickness in 45 hypercholesterolemic subjects with asymptomatic carotid artery disease. Pharmacology 2010;85:63–67.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.