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Hypomagnesemia, obesity and inflammatory cytokines

Magnesium Research. Volume 24, Numéro 1, 19-20, March 2011, Letter to the editor

DOI : 10.1684/mrh.2011.0275

Auteur(s) : Theodor Günther, Charité – Universitlsquätsmedizin Berlin, Campus Benjamin Franklin, Institut für Molekularbiologie und Biochemie, Berlin, Germany.



Auteur(s) : Theodor Günther

Charité – Universitlsquätsmedizin Berlin, Campus Benjamin Franklin, Institut für Molekularbiologie und Biochemie, Berlin, Germany

Correspondence. Prof. Dr. T. Günther, Waldhüterpfad 63, D 14169 Berlin, Germany

In a preceding letter to the editor, I reported that various generations with chronic hypomagnesemia developed hypertension and dyslipidemia but not obesity, insulin resistance and diabetes mellitus type 2 [1]. These results indicate that chronic hypomagnesemia does not induce insulin resistance but hypertension. This conclusion was questioned [2].

Due to an inborn defect of intestinal magnesium (Mg) absorption or renal Mg excretion, chronic hypomagnesemic patients developed cardiomyopathy, convulsions, tetany or neuropsychiatric symptoms but not insulin resistance and diabetes [3, 4].

Chronic hypomagnesemic patients with various forms of the magnesium deficiency syndrome or tetanic syndrome expressed many symptoms but did not develop insulin resistance and diabetes [4-9].

The major risk factor for insulin resistance and type 2 diabetes is obesity. The formation of various adipokines and inflammatory cytokines, among others the formation of IL-1, IL-6 and TNF-α, is increased in obesity [10, 11]. Some of these substances induce the development of insulin resistance [10] and hypertension [11] and contribute to the development of the obesity-induced metabolic syndrome [1, 11].

Increased formation of inflammatory cytokines was also found in Mg-deficient animals. Increased concentrations of IL-1, IL-6 and TNF-α were measured in plasma of hamsters and rats when total plasma Mg concentration was reduced by 70 % to 87 % [12, 13]. Reduction of total plasma Mg by 57 % had no effect on TNF-α in the lungs of Mg-deficient mice [14]. In agreement with these results, TNF-α was increased in the plasma of Mg-deficient rats with graded Mg deficiency when the total plasma Mg concentration was reduced by more than 75% [15].

However, data on the increase in proinflammatory cytokines in blood from Mg-deficient rats are conflicting [14].

In epidemiological and human studies, the effect of Mg on inflammatory markers, insulin resistance and type 2 diabetes was controversial and criticized [10, 16, 17]. In a prospective study with 27,548 individuals, the effect of IL-1β, IL-6 and TNF-α on the development of type 2 diabetes was examined. IL-6 and TNF-α levels were elevated in participants with incident type 2 diabetes. The association between TNF-α and future type 2 diabetes was no longer significant after adjustment for body mass index and waist-to-hip ratio. Mg was not mentioned [18].

An interaction of inflammatory cytokines and Mg in humans may be possible in obese subjects. In obese subjects, TNF-α and serum Mg exhibited an inverse correlation [19]. Possibly the obesity-induced formation of inflammatory cytokines is enhanced by Mg deficiency. An experiment with Zucker fat rats and different Mg statuses could help to clarify the relationship between obesity, Mg and inflammatory cytokines.


1 T. Günther Biochemical mechanisms of the metabolic syndrome and the role of magnesium Magnes Res 2010; 23: 142-145.

2 Y Rayssiguier, E. Rock Commentary to the letter to the editor Magnes Res 2010; 23: 146.

3 Riggs JE, Klingberg WG, Flink EB, Schochet SS, Balian AA, Jenkins III JJ. Cardioskeletal mitochondrial myopathy associated with chronic magnesium deficiency. Neurology 1992; 42: 128-30.

4 Aikawa JK. Magnesium: its biologic significance. CRC Press, Inc. Boca Raton, Florida 1981.

5 Halpern MJ. Magnesium Physiopathology. In: Magnesium deficiency. Halpern MJ, Durlach J, eds. Basel: Karger, 1985: 9-23.

6 Holtmeier HJ. Das Magnesiummangelsyndrom. Stuttgart: Hippokrates Verlag, 1988.

7 Fehlinger R. Therapy with magnesium salts in the tetanic syndrome and associated diseases: a critical appraisal. In: Magnesium, a relevant ion. Lasserre B, Durlach J, eds. London: John Libbey, 1991: 391-404.

8 Durlach J. Magnesium in der klinischen Praxis. Stuttgart: Gustav Fischer Verlag, Jena, 1992.

9 Durlach J. Importance and clinical forms of chronic primary magnesium deficiency in human beings. In: Advances in magnesium research. Rayssiguier Y, Mazur A, Durlach J, eds. London: John Libbey, 2001: 13-20.

10 T. Günther The biochemical function of Mg2+ in insulin secretion, insulin signal transduction and insulin resistance Magnes Res 2010; 23: 5-18.

11 M Vlasova, AK Purhonen, MR Jarvelin, E Rodilla, J Pascual, K.H. Herzig Role of adipokines in obesity-associated hypertension Acta Physiol 2010; 200: 107-127.

12 WB Weglicki, TM Phillips, AM Freedman, MM Cassidy, B.F. Dickens Magnesium-deficiency elevates circulating levels of inflammatory cytokines and endothelin Molec Cell Biochem 1992; 110: 169-173.

13 WB Weglicki, IT Mak, RE Stafford, BF Dickens, MM Cassidy, T.M. Phillips Neurogenic peptides and the cardiomyopathy of magnesium-deficiency: effects of substance P-receptor inhibition Molec Cell Biochem 1994; 130: 103-109.

14 F Sabbagh, F Lecerf, P Maurois, P Bac, M. German-Fattal Severe Mg-deficiency is not associated with endothelial cell activation in mouse lung Magnes Res 2005; 18: 225-234.

15 T Günther, K Schümann, J. Vormann Tumor necrosis factor-α , prostanoids and immunoglobulins in magnesium deficiency Magnes Bull 1995; 17: 109-114.

16 T.J. Orchard Magnesium and type 2 diabetes mellitus Arch Intern Med 1999; 159: 2119-2120.

17 S Bo, E. Pisu Role of dietary magnesium in cardiovascular disease prevention, insulin sensitivity and diabetes Curr Opin Lipidol 2008; 19: 50-56.

18 J Spranger, A Kroke, M Möhlig, K Hoffmann, MM Bergmann, M Ristow, H Boeing, A.F.H. Pfeiffer Inflammatory cytokines and the risk to develop type 2 diabetes Diabetes 2003; 52: 812-817.

19 M Rodríguez-Morán, F. Guerrero-Romero Elevated concentrations of TNF-alpha are related to low serum magnesium levels in obese subjects Magnes Res 2004; 17: 189-196.


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