ARTICLE
Auteur(s) : Yves
Rayssiguier1, Patrycja Libako2, Wojciech
Nowacki2, Edmond Rock1
1INRA, UMR 1019, UNH, CRNH Auvergne, Clermont
Université, Université d'Auvergne, Unité de Nutrition Humaine,
Clermont-Ferrand, France
2Faculty of Veterinary Medicine, Wroclaw University
of Environmental and Life Sciences, Wrocław, Poland
Adequate magnesium (Mg) intake is critical in maintaining Mg
balance and normal Mg-dependent cellular reactions in the human
body. Mg deficiency has been correlated with chronic diseases
including metabolic syndrome [1-7]. A recent hypothesis is
that an inflammatory syndrome induced by Mg deficiency may
represent a triggering factor in the development of metabolic
syndrome [2-7]. The aim of this review is to summarize recent
findings on the role of Mg.
Metabolic syndrome: is Mg deficiency involved?
Interaction between genetic predisposition and a Western-type
lifestyle contributes to the epidemic of metabolic syndrome.
Profound changes in the environment occurred too fast for the
genome to adjust. Hence the emergence of so-called diseases of
civilization [1], first described in agriculture, and that can be
extended in modern food industry. Intensive agriculture has been
related to grass tetany in dairy cows, a disease due to an acute
decrease of plasma magnesium. Similarly, food refining leads to a
reduction of the micronutrient density and thereby induces a
marginal magnesium intake, resulting in a higher prevalence of
Mg deficiency in westernized populations [1]. Even if recent
findings using balance studies suggest a lower Mg requirement than
that estimated previously, the evidence suggests that the
occidental diet is relatively deficient in Mg [1]. Moreover, a
diet rich in animal foods and poor in vegetable foods induces
acidosis and increased Mg urinary excretion [1]. Data from the
National Health and Nutrition Examination Survey (NHANES) showed
that the average intake of magnesium was 350 mg in men, below
the RDA of 420 mg [8]. In the French Supplementation with
antioxidants, vitamins and minerals study (SUVIMAX), 20% of
subjects consumed less than 2/3 of the RDA [9]. Thus, Mg
intake is inadequate in the Western diet, while a higher content of
Mg intake is found in the “prudent diet” as compared to the Western
diet because it also contains more cereals and vegetables [9].
Metabolic syndrome is a condition characterized by a cluster of
several risk factors, including abdominal obesity, insulin
resistance, dyslipidemia and hypertension [2, 4, 5]. This syndrome
and type 2 diabetes are occurring at epidemic rates with
frightful consequences for human health worldwide. In the US, over
40% of people older than 60 years suffer from metabolic
syndrome [10]. Many epidemiological studies have described inverse
relationships between a Mg-rich food intake and diabetes, insulin
resistance and metabolic syndrome [11]. For instance in the Boston
study in young adults with 3 day food record, higher Mg intake
was associated with a 31% lower risk of developing metabolic
syndrome over 15 years of follow up [12]. In the Women's
Health Study, high magnesium status was associated with a 27% of
lower risk of metabolic syndrome [13]. Little is known about the
possible role of Mg in populations in which dietary patterns differ
from Western populations. However, the Shanghai Women's Health
Study suggests that Ca and Mg may protect against the development
of type 2 diabetes [14]. A limitation of observational
studies showing the relationship between dietary Mg intake and
metabolic syndrome is that it can be difficult to separate the
effects of nutrients from those of foods. There is also a strong
association between Mg and other beneficial nutrients: vegetables
fibers, cereals. Thus, the possibility of confounding factors
exists and not all studies confirm the relationship between the Mg
and metabolic syndrome [6]. A recent study indicates that two
common genetic variations in TRPM6 and TRMP7, which play a central
role in Mg homeostasis, might confirm susceptibility to type
2 diabetes in women with low Mg intake [15]. Further studies
are needed to investigate the metabolic consequences of genetic
hypomagnesaemia. Many epidemiological studies indicate that lower
serum Mg levels are associated with insulin resistance and various
components of the metabolic syndrome [16]. Patients with metabolic
syndrome had also lower intramononuclear cell Mg concentration
(which may provide reliable information about intracellular Mg
concentration) as compared to controls. Such findings are also well
documented in patients with diabetes mellitus [17, 18]. Altogether,
the results of these studies suggest plausibility for the
relationship between Mg and metabolic syndrome. The concept that
the metabolic syndrome is an inflammatory condition and that there
are stress-induced inflammation mechanisms [19] brings an exciting
approach to the understanding of this syndrome. Markers including
acute phase proteins, cytokines and mediators have been associated
with endothelial activation [20]. White adipose tissue of obese
individuals is characterized by increased production and secretion
of a wide range of inflammatory molecules involved in macrophage
infiltration, and insulin resistance contribution [20].
Magnesium deficiency modulates stress
and inflammation
The effect of Mg on inflammation-related factors may explain the
association between Mg intake and Mg status on metabolic syndrome
[2, 21]. In humans, an inverse association between markers of
chronic inflammation and Mg intake has been reported on serum
levels [22-25]. The inverse association between Mg and C-reactive
protein suggested that Mg deficiency might be involved in
the development of low chronic inflammatory syndrome, which
can modulate metabolic disorders; Mg supplementation has been shown
to reduce CRP blood levels in patients with heart failure [6].
Even if, in epidemiological studies, the association between Mg and
inflammatory markers is not always evidenced [6], in experimental
animals, there is now a strong biological plausibility for the
direct impact of dietary Mg on inflammation [2, 3]. We will discuss
below the interrelationship between magnesium deficiency, stress,
inflammation and metabolic syndrome (figure 1).
Stress
There is much evidence that stress alone can cause an inflammatory
response. Nervous and immune systems interact bi-directionally. It
is interesting to consider whether stress alone in Mg
deficiency can cause an inflammatory syndrome or whether
dysfunction of the nervous system also participates in the
progression of inflammation. Mg deficiency results in a stressor
effect and increases susceptibility to the physiological damage
produced by stress [26, 27]. Neuromuscular hyperexcitability is a
well known consequence of experimental and clinical Mg-deficiency.
Mg supply has been shown to attenuate the development of adverse
stress reactions. Stress activates the
hypothalamic-pituitary-adrenal axis (HPA) and the sympathetic
nervous system [28]. The activation products are mainly cortisol
and catecholamines. The innervations of the kidney may result in
the production of renin which initiates reactions whereby renin and
angiotensin converting enzymes convert angiotensinogen to
angiotensin II, a powerful vasoconstrictor that elevates the blood
pressure and heart rate [29]. This response has indeed been
documented in experimental animals following Mg deficiency [30].
Experimental Mg deficiency is accompanied by hyperaldosteronism
[31]. There is growing evidence that enhanced activation of the
renin-angiotensin-aldosterone system is a factor in the development
of insulin resistance, by increasing oxidative stress. In both
humans and rats, and in various diseases not directly related to Mg
deficiency, aldosteronism results in an immunostimulatory state and
leads to a proinflammatory phenotype [32]. Moreover,
hyperaldosteronism has been associated with electrolyte
disturbances, including hypomagnesaemia, in relation with TRPM7
downregulation [33]. Peripheral blood mononuclear activation is
induced by a reduction in cytosolic free [Mg2+] and a
subsequent Ca2+ loading that is translated into a
oxidative/nitrosative stress. The latter activation is attenuated
by Mg supplementation but also by preventing Ca loading by Ca
channel blockers. Moreover, we have shown that the pro-inflammatory
phenotype seen in experimental dietary Mg deficiency can be
prevented when a Ca free diet is administered [34]. On the other
hand, a stress response induces the release of large quantities of
excitatory amino acids, such as aspartate and glutamate. Released
glutamate can bind to different receptors, and N-methyl-D-aspartic
acid (NMDA) activation also causes the mobilization of free
cytosolic Ca. Mg deficiency in rats induces hyperalgesia involving
NMDA receptors since MK801, a noncompetitive NMDA receptor
antagonist, prevents hyperalgesia in those animals [35]. Excess
intracellular Ca concentration resulting from Mg deficiency
activates Ca-dependent processes such as the release of cytokines
during stress. At the molecular level, one of the earliest events
in inflammatory stress is the activation of nuclear factor NFκB
[29]. The association of stress with inflammation is strengthened
by the results suggesting that substance P (SP) is also involved in
the response to Mg deficiency [36, 37]. The rise in this
neuropeptide, besides inducing a neurogenic inflammation, may
activate cells including endothelial cells, mast cells, macrophages
and circulating blood cells. Inhibition studies of SP receptor
suggest that the neurogenic peptide contributes to the pathology of
Mg deficiency.
Visceral fat
Visceral obesity represents another important risk factor
associated with metabolic syndrome. Stress-induced HPA axis
activation has been identified to play an important role in this
preferential body fat accumulation and to stimulate the
proinflammatory cytokine secretion by adipocytes that hold a
potentially important pathogenic role. A prominent feature of
the inflammatory process in visceral fat is the presence of
activated macrophages recruited from bone marrow. A number of
activator molecules, such as cortisol, angiotensin II, leptin, and
inhibitor ones, such as adiponectin, are able to promote the
synthesis and secretion of adhesion molecules in endothelium cells
[38]. Evidence that Mg is involved in body weight regulation is
still controversial. Studies have reported either a negative or no
relationship between magnesium and body mass index (BMI). However,
a recent study indicates that men and women with the highest Mg
intake were less likely to be overweight/obese than those with the
lowest intakes – but because Mg is found in a whole range of foods,
it may be the overall dietary pattern and not only Mg intake
that contribute to a lower BMI or lower prevalence of
abdominal adiposity [11].
Endothelium
One of the earliest events in the acute response to stress is
endothelium dysfunction. Endothelial cells actively contribute to
inflammation by elaborating cytokines, by synthesis of chemical
mediators and by expressing adhesion molecules, which bind
leukocytes. In addition, the endothelium cell is sensitive to
cytokines. In vitro, low Mg stimulates the synthesis of IL-1 and
IL-6, NO, a modulator of inflammatory responses, and of VCAM, which
modulates monocyte/endothelial interactions. Mg may suppress
inflammatory responses by human endothelial cells through the NFκB
pathway [39-41].
Clinical symptoms and acute phase response
A characteristic allergy-like crisis with erythema, hyperemia and
edema occurs spontaneously in Mg deficient rats. This response has
been proposed as a model for the screening of anti-inflammatory
substances [2, 3]. The greater spleen size is due to infiltration
with phagocytic cells. An increased number of plasma PMN leukocytes
is observed. One important observation during inflammation is the
production levels of positive and negative acute phase proteins.
The increased IL-6 concentrations are responsible for the synthesis
of many acute phase proteins by the liver such as α2 macroglobulin,
α1 acid glycoprotein, complement, fetoprotein, haptoglobulin and
fibrinogen. The decrease of albumin, apolipoprotein E, and retinol
binding protein (RBP) concentrations is also the consequence of the
acute phase response [2, 3].
Several studies have been performed to assess the activation of
proinflammatory cells in Mg deficiency. Neutrophils and resident
macrophages are more responsive to activation than those of
controls, as shown by respiratory burst studies using
chemiluminescence. Different gene expression analyses of stress
proteins have confirmed the neutrophil activation. The majority of
stress proteins were upregulated in neutrophils from Mg-deficient
animals. Moreover, Mg-deficient rats are more sensitive to immune
stress, as measured by TNF α response, following an endotoxin
challenge. Increasing extracellular Mg concentration in vivo or in
vitro decreased the inflammatory response as shown by
chemiluminiscence studies or cytokine production [2, 3]. Long-term
Mg deficiency also results in inflammation and oxidative stress
[42].
Mg deficiency induces metabolic syndrome in animal
models
Stress and inflammation are involved in the induction and
development of the metabolic syndrome. Several observations
document the effect of Mg deficiency in the development of insulin
resistance in the rat model. Of particular significance is the
observation of the aggravating effect of Mg deficiency on metabolic
syndrome in fructose-fed rats [2]. Increased Mg intake prevents
hyperlipidemia and insulin resistance and reduces lipid
peroxidation in that experimental model [43]. Mg deficiency
contributes to other aspects of the metabolic syndrome:
hyperlipidemia, elevated blood pressure, endothelial dysfunction
and increased thrombosis tendency [2]. Inflammation occurring
during experimental Mg deficiency is the mechanism that induces
hypertriglyceridemia and the proatherogenic changes in lipid
metabolism [3, 44, 45]. Several data indicate that
hypertriglyceridemia, the effect of Mg deficiency, can be
suppressed or reduced by decreasing the inflammatory response [34].
Metabolic syndrome also leads to enhanced blood clotting, likely
resulting from endothelial dysfunction and dyslipidemia, which
trigger platelet aggregation, thereby increasing the risk of
thrombotic events [46, 47]. TRPM7 dysregulation, that may be a
critical regulator of Mg homeostasis in vascular cells, is
associated with endothelial dysfunction in mice selected for low
intracellular Mg. Thus, low Mg intake or genetic hypomagnesemia may
induce endothelial dysfunction [48]. Epidemiological and
experimental studies have demonstrated an inverse association
between magnesium status and blood pressure [31]. Chronic dietary
magnesium deficiency causes elevated blood pressure; initially a
hypotension phase is observed, which is due to the release of
inflammatory agents, the subsequent hypertension is a result of
oxidative stress and structural modifications in the vascular
system [31]. In fact, inactivation of nitric oxide contributes to
hypertension during chronic Mg deficiency, by decreasing the
relaxing property of nitric oxide [31].
Which mechanism is responsible?
A cellular Mg deficiency exaggerates Ca-induced cell stimulation
and extracellular Mg acts as a non-specific antagonist of various
Ca channels. Elevation of Ca2+ with a reciprocal
decrease in Mg2+ is consistently seen in subjects with
hypertension, obesity and NIDDM. According to Resnick [17], the
clinical abnormalities associated with metabolic syndrome may be
related to this ionic defect. The inflammatory response induces
activation of several processes, which are dependent on cytosolic
Ca2+ elevation.
Enhanced Ca2+ response of macrophages
from Mg-deficient rats
Resident macrophages from Mg-deficient rats are activated and there
is an enhanced Ca2+ response after in vitro stimulation.
This occurs very early in the course of the deficiency [49].
Effect of Ca antagonists on neutrophil respiratory
burst
Neutrophils from mice activated with PMA showed an increased
respiratory burst when incubated in low Mg concentration (0.1 mM)
as compared to normal Mg concentration (1 mM). We have investigated
the effect of intracellular (TMB-8) and extracellular (verapamil)
Ca channel blockers. These antagonists were more effective in
decreasing oxidative burst when cells were incubated in low-Mg
medium than in a medium with a normal concentration. Verapamil did
not decrease the respiratory burst in normal medium.
A decrease was observed when cells were treated with both
verapamil and TMB-8. By contrast, both verapamil and TMB-8 reduced
the oxidative burst of cells in low Mg medium. With the association
verapamil plus TMB-8, the decrease was significantly more important
than observed in normal medium. The effect of Ca antagonists
supports the hypothesis that Ca is the intracellular modulator
involved in the inflammatory response induced by Mg-deficiency
[50].
Inhibition of inflammatory responses by Ca intake
modification in vivo
A recent study was performed in vivo to assess if an inflammatory
effect of Mg is the consequence of a reduced extracellular Mg/Ca
antagonism [34]. Adaptation to a low-Ca diet is impaired by Mg
deficiency and hypocalcaemia is a manifestation of Mg deficiency
when rats are fed a Ca- deficient diet. The inflammatory response
(hyperemia, leukocytosis) is dramatically reduced in Mg deficient
rats when there is a concomitant decrease in plasma Ca levels. On
the other hand, recent observations suggesting that there is a
relationship between parathyroid hormone, Ca intake and metabolic
syndrome in human subjects is of particular interest [51].
Beneficial effect of Ca antagonists on mortality
of Mg-deficient mice
It is known than Ca channel blockers can be used to treat patients
with metabolic syndrome. The potential beneficial effect of Ca
antagonists has been investigated in Mg-deficient mice [52]. About
65% of Mg-deficient mice died within 30 days, in contrast all
the nifedipine-treated mice survived for 30 days. This
experiment does not provide information on a potential
anti-inflammatory effect of Ca antagonists in Mg deficiency but
these findings suggest that a Ca antagonist may play a compensatory
role for Mg as natural physiological blocker. In Mg-deficient rats,
a decreased acute stress reaction has also been described
after Ca antagonist treatment [52]. To conclude, a Mg effect on
Ca2+ homeostasis may be a common link between stress,
inflammation and metabolic syndrome.
Disclosure
None of the authors has any conflict of interest to disclose.
References
1 Rayssiguier Y, Mazur A, Durlach J. Advances in Magnesium Research
Nutrition & Health. London: John Libbey, 2001. 504 p.
2 Rayssiguier Y, Gueux E, Nowacki W, Rock E,
Mazur A. High fructose consumption combined with low dietary
magnesium intake may increase the incidence of the metabolic
syndrome by inducing inflammation. Magnes Res 2006; 19: 237-43.
3 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.
4 Barbagallo M, Dominguez LJ. Magnesium metabolism in
type 2 diabetes mellitus, metabolic syndrome and insulin
resistance. Arch Biochem Biophys 2007; 458: 40-7.
5 Belin RJ, He K. Magnesium physiology and pathogenic
mechanisms that contribute to the development of the metabolic
syndrome. Magnes Res 2007; 20: 107-29.
6 Bo S, Pisu E. Role of dietary magnesium in
cardiovascular disease prevention, insulin sensitivity and
diabetes. Curr Opin Lipidol 2008; 19: 50-6.
7 Barbagallo M, Belvedere M, Dominguez LJ.
Magnesium homeostasis and aging. Magnes Res 2009; 22: 235-46.
8 Ford ES, Mokdad AH. Dietary magnesium intake in a
national sample of US adults. J Nutr 2003; 133: 2879-82.
9 Galan P, Preziosi P, Durlach V, Valeix P,
Ribas L, Bouzid D, Favier A, Hercberg S.
Dietary magnesium intake in a French adult population. Magnes Res
1997; 10: 321-8.
10 Ford ES, Giles WH, Mokdad AH. Increasing
prevalence of the metabolic syndrome among U.S. adults. Diabetes
Care 2004; 27: 2444-9.
11 McKeown NM, Jacques PF, Zhang XL, Juan W,
Sahyoun NR. Dietary magnesium intake is related to metabolic
syndrome in older Americans. Eur J Nutr 2008; 47: 210-6.
12 He K, Liu K, Daviglus ML, Morris SJ,
Loria CM, Van Horn L, Jacobs Jr DR,
Savage PJ. Magnesium intake and incidence of metabolic
syndrome among young adults. Circulation 2006; 113: 1675-82.
13 Song Y, Manson JE, Buring JE, Liu S.
Dietary magnesium intake in relation to plasma insulin levels and
risk of type 2 diabetes in women. Diabetes Care 2004; 27:
59-65.
14 Villegas R, Gao YT, Dai Q, Yang G,
Cai H, Li H, Zheng W, Shu XO. Dietary calcium
and magnesium intakes and the risk of type 2 diabetes: the
Shanghai Women's Health Study. Am J Clin Nutr 2009; 89:
1059-67.
15 Song Y, Hsu YH, Niu T, Manson JE,
Buring JE, Liu S. Common genetic variants of the ion
channel transient receptor potential membrane melastatin 6 and
7 (TRPM6 and TRPM7), magnesium intake, and risk of type
2 diabetes in women. BMC Med Genet 2009; 10: 4.
16 Evangelopoulos AA, Vallianou NG,
Panagiotakos DB, Georgiou A, Zacharias GA,
Alevra AN, Zalokosta GJ, Vogiatzakis ED,
Avgerinos PC. An inverse relationship between cumulating
components of the metabolic syndrome and serum magnesium levels.
Nutr Res 2008; 28: 659-63.
17 Resnick LM. Ionic basis of hypertension, insulin
resistance, vascular disease, and related disorders. The mechanism
of “syndrome X”. Am J Hypertens 1993; 6: 123S-134S.
18 Lima Mde L, Cruz T, Rodrigues LE,
Bomfim O, Melo J, Correia R, Porto M,
Cedro A, Vicente E. Serum and intracellular magnesium
deficiency in patients with metabolic syndrome--evidences for its
relation to insulin resistance. Diabetes Res Clin Pract 2009; 83:
257-62.
19 Dandona P, Aljada A, Bandyopadhyay A.
Inflammation: the link between insulin resistance, obesity and
diabetes. Trends Immunol 2004; 25: 4-7.
20 Bastard JP, Maachi M, Lagathu C, Kim MJ,
Caron M, Vidal H, Capeau J, Feve B. Recent
advances in the relationship between obesity, inflammation, and
insulin resistance. Eur Cytokine Netw 2006; 17: 4-12.
21 Guerrero-Romero F, Rodriguez-Moran M.
Hypomagnesemia, oxidative stress, inflammation, and metabolic
syndrome. Diabetes Metab Res Rev 2006; 22: 471-6.
22 Bo S, Durazzo M, Guidi S, Carello M,
Sacerdote C, Silli B, Rosato R, Cassader M,
Gentile L, Pagano G. Dietary magnesium and fiber intakes
and inflammatory and metabolic indicators in middle-aged subjects
from a population-based cohort. Am J Clin Nutr 2006; 84:
1062-9.
23 Song Y, Ridker PM, Manson JE, Cook NR,
Buring JE, Liu S. Magnesium intake, C-reactive protein,
and the prevalence of metabolic syndrome in middle-aged and older
U.S. women. Diabetes Care 2005; 28: 1438-44.
24 Rodriguez-Moran M, Guerrero-Romero F. Elevated
concentrations of TNF-alpha are related to low serum magnesium
levels in obese subjects. Magnes Res 2004; 17: 189-96.
25 Song Y, Li TY, van Dam RM, Manson JE,
Hu FB. Magnesium intake and plasma concentrations of markers
of systemic inflammation and endothelial dysfunction in women. Am J
Clin Nutr 2007; 85: 1068-74.
26 Classen HG. Stress and magnesium. Artery 1981; 9:
182-9.
27 Durlach J. Magnesium in clinical practice. London: John
Libbey.
28 Munhoz CD, Garcia-Bueno B, Madrigal JL,
Lepsch LB, Scavone C, Leza JC. Stress-induced
neuroinflammation: mechanisms and new pharmacological targets. Braz
J Med Biol Res 2008; 41: 1037-46.
29 Black PH. The inflammatory consequences of psychologic
stress: relationship to insulin resistance, obesity,
atherosclerosis and diabetes mellitus, type II. Med Hypotheses
2006; 67: 879-91.
30 Cantin M. Relationship of juxtaglomerular apparatus and
adrenal cortex to biochemical and extracellular fluid volume
changes in magnesium deficiency. Lab Invest 1970; 22: 558-68.
31 Laurant P, Dalle M, Berthelot A,
Rayssiguier Y. Time-course of the change in blood pressure
level in magnesium-deficient Wistar rats. Br J Nutr 1999; 82:
243-51.
32 Ahokas RA, Sun Y, Bhattacharya SK,
Gerling IC, Weber KT. Aldosteronism and a proinflammatory
vascular phenotype: role of Mg2+, Ca2+, and
H2O2 in peripheral blood mononuclear cells.
Circulation 2005; 111: 51-7.
33 Sontia B, Montezano AC, Paravicini T,
Tabet F, Touyz RM. Downregulation of renal TRPM7 and
increased inflammation and fibrosis in aldosterone-infused mice:
effects of magnesium. Hypertension 2008; 51: 915-21.
34 Bussiere FI, Gueux E, Rock E, Mazur A,
Rayssiguier Y. Protective effect of calcium deficiency on the
inflammatory response in magnesium-deficient rats. Eur J Nutr 2002;
41: 197-202.
35 Begon S, Pickering G, Eschalier A,
Mazur A, Rayssiguier Y, Dubray C. Role of spinal
NMDA receptors, protein kinase C and nitric oxide synthase in the
hyperalgesia induced by magnesium deficiency in rats. Br J
Pharmacol 2001; 134: 1227-36.
36 O'Connor TM, O'Connell J, O'Brien DI,
Goode T, Bredin CP, Shanahan F. The role of
substance P in inflammatory disease. J Cell Physiol 2004; 201:
167-80.
37 Weglicki WB, Chmielinska JJ, Tejero-Taldo I,
Kramer JH, Spurney CF, Viswalingham K, Lu B,
Mak IT. Neutral endopeptidase inhibition enhances substance P
mediated inflammation due to hypomagnesemia. Magnes Res 2009; 22:
167S-173S.
38 Fantuzzi G. Adipose tissue, adipokines, and
inflammation. J Allergy Clin Immunol 2005; 115: 911-9.
39 Bernardini D, Nasulewicz A, Mazur A,
Maier JA. Magnesium and microvascular endothelial cells: a
role in inflammation and angiogenesis. Front Biosci 2005; 10:
1177-82.
40 Maier JA, Malpuech-Brugere C, Zimowska W, Rayssiguier Y,
Mazur A. Low magnesium promotes endothelial cell dysfunction:
implications for atherosclerosis, inflammation and thrombosis.
Biochim Biophys Acta 2004; 1689: 13-21.
41 Rochelson B, Dowling O, Schwartz N,
Metz CN. Magnesium sulfate suppresses inflammatory responses
by human umbilical vein endothelial cells (HuVECs) through the
NFkappaB pathway. J Reprod Immunol 2007; 73: 101-7.
42 Blache D, Devaux S, Joubert O, Loreau N,
Schneider M, Durand P, Prost M, Gaume V,
Adrian M, Laurant P, Berthelot A. Long-term moderate
magnesium-deficient diet shows relationships between blood
pressure, inflammation and oxidant stress defense in aging rats.
Free Radic Biol Med 2006; 41: 277-84.
43 Olatunji LA, Soladoye AO. Increased magnesium
intake prevents hyperlipidemia and insulin resistance and reduces
lipid peroxidation in fructose-fed rats. Pathophysiology 2007; 14:
11-5.
44 Rayssiguier Y, Noe L, Etienne J, Gueux E,
Cardot P, Mazur A. Effect of magnesium deficiency on
postheparin lipase activity and tissue lipoprotein-lipase in the
rat. Lipids 1991; 26: 182-6.
45 Bussiere L, Mazur A, Gueux E, Nowacki W,
Rayssiguier Y. Triglyceride-rich lipoproteins from
magnesium-deficient rats are more susceptible to oxidation by cells
and promote proliferation of cultured vascular smooth muscle cells.
Magnes Res 1995; 8: 151-7.
46 Rayssiguier Y, Gueux E. Magnesium and lipids in
cardiovascular disease. J Am Coll Nutr 1986; 5: 507-19.
47 Nieuwdorp M, Stroes ES, Meijers JC,
Buller H. Hypercoagulability in the metabolic syndrome. Curr
Opin Pharmacol 2005; 5: 155-9.
48 Paravicini TM, Yogi A, Mazur A, Touyz RM.
Dysregulation of vascular TRPM7 and annexin-1 is associated with
endothelial dysfunction in inherited hypomagnesemia. Hypertension
2009; 53: 423-9.
49 Malpuech-Brugere C, Rock E, Astier C,
Nowacki W, Mazur A, Rayssiguier Y. Exacerbated
immune stress response during experimental magnesium deficiency
results from abnormal cell calcium homeostasis. Life Sci 1998; 63:
1815-22.
50 Libako P, Nowacki W, Rock E,
Rayssiguier Y, Mazur A. Phagocyte priming by low
magnesium status: input to the enhanced inflammatory and oxidative
stress responses. Magnes Res 2010; 23: 1-4.
51 Hjelmesaeth J, Hofso D, Aasheim ET,
Jenssen T, Moan J, Hager H, Roislien J,
Bollerslev J. Parathyroid hormone, but not vitamin D, is
associated with the metabolic syndrome in morbidly obese women and
men: a cross-sectional study. Cardiovasc Diabetol 2009; 8: 7.
52 Sakaguchi H, Sakaguchi R, Ishiguro S,
Nishio A. Beneficial effects of a calcium antagonist,
nifedipine, on death and cardiovascular calcinosis induced by
dietary magnesium deficiency in adult mice. Magnes Res 1992; 5:
121-5.
|
Version imprimable
Version PDF
