Objectives: The aim of the present study was to determine the efficacy of oral magnesium (Mg) supplementation on endothelial function through evaluation of carotid intima-media thickness (cIMT), brachial artery flow-mediated dilatation (FMD), and C-reactive protein (CRP) among hemodialysis (HD) patients. Methods: This randomized, controlled, double-blind clinical trial consisted of 54 patients on HD. One group was treated orally with 440 mg of Mg oxide 3 times per week for 6 months (n = 29). The control group (n = 25) was given placebo using the same administration protocol. cIMT, FMD, serum calcium levels, phosphorus, lipid, CRP, and bicarbonate were measured at baseline and at 6 months in both groups. Results: At 6 months, cIMT was significantly decreased in the Mg group (0.84 ± 0.13 mm at baseline and 0.76 ± 0.13 mm at 6 months, p = 0.001). However, in the placebo group, cIMT was significantly increased (0.73 ± 0.13 and 0.79 ± 0.12 mm, respectively, p = 0.003). When hypertension, diabetes mellitus, smoking, hyperlipidemia, and systemic lupus erythematosus were controlled for in the analysis, the effect of Mg remained significant in both groups (p = 0.000). Conclusion: Our results indicate that Mg might not improve endothelial function (CRP level and FMD) and that a decreased cIMT as a marker of atherosclerosis may be due to the inhibition of calcification through the regulation parathormone, calcium, and phosphorus.

1.
Collins AJ, Foley RN, Herzog C, Gilbertson D, Ishani A, Kasiske BL, Liu J, Mau LW, McBean M, Murray A, St Peter W, Guo H, Li Q, Li S, Li S, Peng Y, Qiu Y, Roberts T, Skeans M, Snyder J, Solid C, Wang C, Weinhandl E, Zaun D, Arko C, Chen SC, Dalleska F, Daniels F, Dunning S, Ebben J, Frazier E, Hanzlik C, Johnson R, Sheets D, Wang X, Forrest B, Constantini E, Everson S, Eggers PW, Agodoa L: Excerpts from the US Renal Data System 2009 Annual Data Report. Am J Kidney Dis 2010;55:S1–S7.
2.
Foley RN, Parfrey PS, Sarnak MJ: Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis 1998;32:S112–S119.
3.
Vanholder R, Meert N, Schepers E, Glorieux G, Argiles A, Brunet P: Review on uraemic solutes II–variability in reported concentrations: causes and consequences. Nephrol Dial Transplant 2007;22:3115–3121.
4.
Matsuoka M, Iseki K, Tamashiro M, Fujimoto N, Higa N, Touma T, Takishita S: Impact of high coronary artery calcification score (CACS) on survival in patients on chronic hemodialysis. Clin Exp Nephrol 2004;8:54–58.
5.
London GM, Guerin AP, Marchais SJ, Métivier F, Pannier B, Adda H: Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant 2003;18:1731–1740.
6.
Block GA, Raggi P, Bellasi A, Kooienga L, Spiegel DM: Mortality effect of coronary calcification and phosphate binder choice in incident hemodialysis patients. Kidney Int 2007;71:438–441.
7.
Blacher J, Guerin AP, Pannier B, Marchais SJ, London GM: Arterial calcifications, arterial stiffness, and cardiovascular risk in end-stage renal disease. Hypertension 2001;38:938–942.
8.
Block GA, Hulbert-Shearon TE, Levin NW, Port FK: Association of serum phosphorus and calcium x phosphate product with mortality risk in chronic hemodialysis patients: a national study. Am J Kidney Dis 1998;31:607–617.
9.
Ganesh SK, Stack AG, Levin NW, Hulbert-Shearon T, Port FK: Association of elevated serum PO(4), Ca x PO(4) product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients. J Am Soc Nephrol 2001;12:2131–2138.
10.
Ennever J, Vogel JJ: Magnesium inhibition of apatite nucleation by proteolipid. J Dent Res 1981;60:838–841.
11.
Wei M, Esbaei K, Bargman J, Oreopoulos DG: Inverse correlation between serum magnesium and parathyroid hormone in peritoneal dialysis patients: a contributing factor to adynamic bone disease? Int Urol Nephrol 2006;38:317–322.
12.
Wei M, Esbaei K, Bargman JM, Oreopoulos DG: Relationship between serum magnesium, parathyroid hormone, and vascular calcification in patients on dialysis: a literature review. Perit Dial Int 2006;26:366–373.
13.
Ma J, Folsom AR, Melnick SL, Eckfeldt JH, Sharrett AR, Nabulsi AA: Associations of serum and dietary magnesium with cardiovascular disease, hypertension, diabetes, insulin, and carotid arterial wall thickness: the ARIC study. Atherosclerosis Risk in Communities Study. J Clin Epidemiol 1995;48:927–940.
14.
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.
15.
Bots ML, Hoes AW, Koudstaal PJ, Hofman A, Grobbee DE: Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study. Circulation 1997;96:1432–1437.
16.
Tzanakis I, Virvidakis K, Tsomi A, Mantakas E, Girousis N, Karefyllakis N, et al: Intra- and extracellular magnesium levels and atheromatosis in haemodialysis patients. Magnes Res 2004;17:102–108.
17.
Lindeman RD: Chronic renal failure and magnesium metabolism. Magnesium 1986;5:293–300.
18.
Thijssen DH, Black MA, Pyke KE, Padilla J, Atkinson G, Harris RA, Parker B, Widlansky ME, Tschakovsky ME, Green DJ: Assessment of flow mediated dilation (FMD) in humans: a methodological and technical guideline. Am J Physiol Heart Circ Physiol 2011;300:H2–H12.
19.
Janssens SP, Shimouchi A, Quertermous T, Bloch DB, Bloch KD: Cloning and expression of a cDNA encoding human endothelium-derived relaxing factor/nitric oxide synthase. J Biol Chem 1992;267:14519–14522.
20.
Ghiadoni L, Versari D, Giannarelli C, Faita F, Taddei S: Non-invasive diagnostic tools for investigating endothelial dysfunction. Curr Pharm Des 2008;14:3715–3722.
21.
Devaraj S, Singh U, Jialal I: The evolving role of C-reactive protein in atherothrombosis. Clin Chem 2009;55:229–238.
22.
Fabbian F, Cacici G, Franceschini L, Russo G, Vassanelli C, Catizone L, Lupo A: The relationship between carotid and coronary atherosclerotic damage in dialysis patients. Int J Artif Organs 2007;30:315–320.
23.
Maier JA: Low magnesium and atherosclerosis: an evidence-based link. Mol Aspects Med 2003;24:137–146.
24.
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. Atherosclerosis Risk in Communities Study. J Clin Epidemiol 1995;48:927–940.
25.
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.
26.
Baldassarre D, De JA, Amato M, Werba JP, Castelnuovo S, Frigerio B, Veglia F, Tremoli E, Sirtori CR: Carotid intima-media thickness and markers of inflammation, endothelial damage and hemostasis. Ann Med 2008;40:21–44.
27.
Montecucco F, Mach F: New evidences for C-reactive protein (CRP) deposits in the arterial intima as a cardiovascular risk factor. Clin Interv Aging 2008;3:341–349.
28.
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.
29.
Nishizawa Y, Shoji T, Kawagishi T, Morii H: Atherosclerosis in uremia: possible roles of hyperparathyroidism and intermediate density lipoprotein accumulation. Kidney Int Suppl 1997;62:S90–S92.
30.
Wei M, Esbaei K, Bargman J, Oreopoulos DG: Relationship between serum magnesium, parathyroid hormone, and vascular calcification in patients on dialysis: a literature review. Perit Dial Int 2006;26:366–373.
31.
Meema HE, Oreopoulos DG, Rapoport A: Serum magnesium level and arterial calcification in end-stage renal disease. Kidney Int 1987;32:388–394.
32.
Ouchi Y, Tabata RE, Stergiopoulos K, Sato F, Hattori A, Orimo H: Effect of dietary magnesium on development of atherosclerosis in cholesterol-fed rabbits. Arteriosclerosis 1990;10:732–737.
33.
Orimo H, Ouchi Y: The role of calcium and magnesium in the development of atherosclerosis. Experimental and clinical evidence. Ann NY Acad Sci 1990;598:444–457.
34.
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.
35.
Neglen P, Qvarfordt P, Eklof B: Peroral magnesium hydroxide therapy and intermittent claudication – a preliminary report. Vasa 1985;14:285–288.
36.
Abbott RD, Ando F, Masaki KH, Tung KH, Rodriguez BL, Petrovitch H: Dietary magnesium intake and the future risk of coronary heart disease (the Honolulu Heart Program). Am J Cardiol 2003;92:665–669.
37.
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.
38.
Malpuech-Brugere C, Nowacki W, Gueux E, Kuryszko J, Rock E, Rayssiguier Y, Mazur A: Accelerated thymus involution in magnesium-deficient rats is related to enhanced apoptosis and sensitivity to oxidative stress. Br J Nutr 1999;81:405–411.
39.
Touyz RM: Role of magnesium in the pathogenesis of hypertension. Mol Aspects Med 2003;24:107–136.
40.
Rukshin V, Azarbal B, Shah PK, Tsang VT, Shechter M, Finkelstein A, Cercek B, Kaul S: Intravenous magnesium in experimental stent thrombosis in swine. Arterioscler Thromb Vasc Biol 2001;21:1544–1549.
41.
Altura BM, Altura BT, Gebrewold A, et al: Magnesium deficiency and hypertension: correlation between magnesium-deficient diets and microcirculatory changes in situ. Science 1984;223:1315–1317.
42.
Boskey AL, Posner AS: Effect of magnesium on lipid-induced calcification: an in vitro model for bone mineralization. Calcif Tissue Int 1980;32:139–143.
43.
Navarro JF, Mora C, Jimenez A, Torres A, Macía M, García J: Relationship between serum magnesium and parathyroid hormone levels in hemodialysis patients. Am J Kidney Dis 1999;34:43–48.
44.
Navarro-Gonzalez JF: Magnesium in dialysis patients: serum levels and clinical implications. Clin Nephrol 1998;49:373–378.
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.