ArticlePDF Available

Magnesium Basics

Authors:

Abstract and Figures

As a cofactor in numerous enzymatic reactions, magnesium fulfils various intracellular physiological functions. Thus, imbalance in magnesium status—primarily hypomagnesaemia as it is seen more often than hypermagnesaemia—might result in unwanted neuromuscular, cardiac or nervous disorders. Measuring total serum magnesium is a feasible and affordable way to monitor changes in magnesium status, although it does not necessarily reflect total body magnesium content. The following review focuses on the natural occurrence of magnesium and its physiological function. The absorption and excretion of magnesium as well as hypo- and hypermagnesaemia will be addressed.
Content may be subject to copyright.
Clin Kidney J (2012) 5[Suppl 1]: i3–i14
doi: 10.1093/ndtplus/sfr163
Magnesium basics
Wilhelm Jahnen-Dechent
1
and Markus Ketteler
2
1
RWTH Aachen University, Helmholtz Institute for Biomedical Engineering, Biointerface Laboratory, Aachen, Germany and
2
Klinikum
Coburg, III. Medizinische Klinik, Coburg, Germany
Correspondence and offprint requests to: Wilhelm Jahnen-Dechent; E-mail: willi.jahnen@rwth-aachen.de
Abstract
As a cofactor in numerous enzymatic reactions, magnesium fulfils various intracellular physiological
functions. Thus, imbalance in magnesium status—primarily hypomagnesaemia as it is seen more
often than hypermagnesaemia—might result in unwanted neuromuscular, cardiac or nervous dis-
orders. Measuring total serum magnesium is a feasible and affordable way to monitor changes in
magnesium status, although it does not necessarily reflect total body magnesium content. The
following review focuses on the natural occurrence of magnesium and its physiological function.
The absorption and excretion of magnesium as well as hypo- and hypermagnesaemia will be
addressed.
Keywords: magnesium; physicochemical properties; physiological function; regulation; hypomagnesaemia;
hypermagnesaemia
Introduction
Magnesium is the eighth most common element in the
crust of the Earth [1,2] and is mainly tied up within mineral
deposits, for example as magnesite (magnesium carbo-
nate [MgCO
3
]) and dolomite. Dolomite CaMg(CO
3
)
2
is, as
the name suggests, abundant in the Dolomite mountain
range of the Alps [3]. The most plentiful source of biolog-
ically available magnesium, however, is the hydrosphere
(i.e. oceans and rivers). In the sea, the concentration of
magnesium is ~55 mmol/L and in the Dead Sea—as an
extreme example—the concentration is reported to be
198 mmol/L magnesium [4] and has steadily increased
over time.
Magnesium salts dissolve easily in water and are much
more soluble than the respective calcium salts. As a result,
magnesium is readily available to organisms [5]. Magne-
sium plays an important role in plants and animals alike
[2]. In plants, magnesium is the central ion of chlorophyll
[3]. In vertebrates, magnesium is the fourth most abun-
dant cation [5,6] and is essential, especially within cells,
being the second most common intracellular cation after
potassium, with both these elements being vital for nu-
merous physiological functions [69]. Magnesium is also
used widely for technical and medical applications ranging
from alloy production, pyrotechnics and fertilizers to
health care. Traditionally, magnesium salts are used as
antacids or laxatives in the form of magnesium hydroxide
[Mg(OH)
2
], magnesium chloride (MgCl
2
), magnesium cit-
rate (C
6
H
6
O
7
Mg) or magnesium sulphate (MgSO
4
).
Chemical characteristics
Magnesium is a Group 2 (alkaline earth) element within the
periodic table and has a relative atomic mass of 24.305 Da
[7], a specific gravity at 20!C of 1.738 [2,3], a melting point
of 648.8!C[2] and a boiling point of 1090!C[3]. In the
dissolved state, magnesium binds hydration water tighter
than calcium, potassium and sodium. Thus, the hydrated
magnesium cation is hard to dehydrate. Its radius is ~400
times larger than its dehydrated radius. This difference
between the hydrated and the dehydrated state is much
more prominent than in sodium (~25-fold), calcium (~25-
fold) or potassium (4-fold) [5]. Consequently, the ionic ra-
dius of dehydrated magnesium is small but biologically
relevant [6]. This simple fact explains a lot of magnesium’s
peculiarities, including its often antagonistic behaviour to
calcium, despite similar chemical reactivity and charge. For
instance, it is almost impossible for magnesium to pass
through narrow channels in biological membranes that
can be readily traversed by calcium because magnesium,
unlike calcium, cannot be easily stripped of its hydration
shell [10]. Steric constraints for magnesium transporters
are also far greater than for any other cation transport
system [5]: proteins transporting magnesium are required
to recognize the large hydrated cation, strip off its hydra-
tion shell and deliver the bare (i.e. dehydrated) ion to the
transmembrane transport pathway through the mem-
brane (Figure 1)[5,11,12]. There are obvious chemical
similarities between calcium and magnesium but in cell
biology, major differences often prevail (Table 1).
Physiological role of magnesium in the body
The body of most animals contains ~0.4 g magnesium/kg
[5]. The total magnesium content of the human body is
reported to be ~20 mmol/kg of fat-free tissue. In other
words, total magnesium in the average 70 kg adult with
20% (w/w) fat is ~1000 [7] to 1120 mmol [13] or ~24 g [14,
15]. These values should be interpreted with caution, how-
ever, as analytical methods differ considerably through-
out the years. In comparison, the body content of calcium
"The Author 2012. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
For permissions, please e-mail: journals.permissions@oup.com
at RWTH Aachen, on March 4, 2012http://ckj.oxfordjournals.org/Downloaded from
is ~1000 g (i.e. 42 times greater than the body content of
magnesium) [16].
Distribution in the human body
About 99% of total body magnesium is located in bone,
muscles and non-muscular soft tissue [17] (see also Table
2). Approximately 50–60% of magnesium resides as sur-
face substituents of the hydroxyapatite mineral compo-
nent of bone [14,18]. An illustration of bioapatite is
shown in Figure 2. Most of the remaining magnesium is
contained in skeletal muscle and soft tissue [14]. The mag-
nesium content of bone decreases with age, and magne-
sium stored in this way is not completely bioavailable
during magnesium deprivation [5]. Nonetheless, bone pro-
vides a large exchangeable pool to buffer acute changes in
serum magnesium concentration [19]. Overall, one third of
skeletal magnesium is exchangeable, serving as a reservoir
for maintaining physiological extracellular magnesium
levels [19].
Intracellular magnesium concentrations range from 5 to
20 mmol/L; 1–5% is ionized, the remainder is bound to
proteins, negatively charged molecules and adenosine tri-
phosphate (ATP) [18].
Extracellular magnesium accounts for ~1% of total body
magnesium [14,18,20] which is primarily found in serum
and red blood cells (RBCs) [5,7,21,22]. Serum magnesium
can—just like calcium—be categorized into three frac-
tions. It is either free/ionized, bound to protein or com-
plexed with anions such as phosphate, bicarbonate and
citrate or sulphate (Table 1,Figure 3). Of the three fractions
in plasma, however, ionized magnesium has the greatest
biological activity [5,7,21,22].
Fig. 1. (Aand B) Magnesium (top left) is surrounded by two hydration shells,
whereas calcium (top right) has just one layer. If elements need to fit into a
structure (transporter or membrane ‘pore’), calcium (below right) simply
sheds its hydration shell and its dehydrated ion will fit. Magnesium (below
left), on the other hand, first has to get rid of two layers, which is highly
energy consuming (simplified model).
Table 1. Comparison of magnesium and calcium differences and similarities [1–3, 5, 7, 10, 16, 21, 23–27]
Magnesium Calcium
Chemical aspects
Name (symbol) Magnesium (Mg) Calcium (Ca)
Element category Alkaline earth metal Alkaline earth metal
Abundance Eighth most abundant element in the crust
of the Earth
Fifth most abundant element in the crust of the Earth
Atomic number 12 20
Valence 2 2
Crystal structure Hexagonal Face-centered cubic
Atomic radius 0.65 Å 0.94 Å
Atomic weight 24.305 g/mol 40.08 g/mol
Specific gravity 1.738 (20!C) 1.55 (20!C)
Number of hydration shells Two layers One layer
Radius after hydration ~400 3larger than its dehydrated form ~25 3larger than its dehydrated form
Isotopes Magnesium naturally exists in three stable isotopes: Calcium has five stable isotopes:
[24]
Mg (most abundant isotope)
[40]
Ca (most abundant isotope)
[25]
Mg
[42]
Ca
[26]
Mg
[43]
Ca
[28]
Mg radioactive, b-decay
[44]
Ca
[46]
Ca
Physiological aspects
Availability in the human body Normal serum concentration range:
0.65–1.05 mmol/L, divided into three fractions:
Normal serum concentration range: 2.2–2.6 mmol/L,
divided into three fractions:
Free, ionized (ultrafilterable fraction): 55–70% Free, ionized (ultrafilterable fraction): 47.5–50%
Protein-bound (non-ultrafilterable): 20–30% Protein-bound (non-ultrafilterable): 42–46%
Complexed (citrate, bicarbonate, phosphate): 5–15% Complexed (citrate, bicarbonate, phosphate): 6.0–6.5%
Tot al b ody c on te nt in a du lts ~24 g ~1000 g
Function with respect to cell death Anti-apoptotic Pro-apoptotic
Information attained by serum level Serum level does not represent total body content Serum level does not represent total body content
i4 W. Jahnen-Dechent and M. Ketteler
at RWTH Aachen, on March 4, 2012http://ckj.oxfordjournals.org/Downloaded from
Magnesium is primarily found within the cell [7] where it
acts as a counter ion for the energy-rich ATP and nuclear
acids. Magnesium is a cofactor in >300 enzymatic reac-
tions [8,10]. Magnesium critically stabilizes enzymes, in-
cluding many ATP-generating reactions [14]. ATP is
required universally for glucose utilization, synthesis of
fat, proteins, nucleic acids and coenzymes, muscle con-
traction, methyl group transfer and many other processes,
and interference with magnesium metabolism also influ-
ences these functions [14]. Thus, one should keep in mind
that ATP metabolism, muscle contraction and relaxation,
normal neurological function and release of neurotrans-
mitters are all magnesium dependent. It is also important
to note that magnesium contributes to the regulation of
vascular tone, heart rhythm, platelet-activated thrombosis
and bone formation (see review by Cunningham et al. [28]
in this supplement) [6,7,10,29,30]. Some of magnesium’s
many functions are listed in Table 3.
In muscle contraction, for example, magnesium stimu-
lates calcium re-uptake by the calcium-activated ATPase
of the sarcoplasmic reticulum [14]. Magnesium further
modulates insulin signal transduction and cell proliferation
Table 2. Distribution of magnesium in the adult human being, molar mass
of magnesium ¼24.305 g/mol; Reprinted from [7], with permission from
Elsevier
Tissue
Body weight
(kg wet
weight)
Concentration
(mmol/kg wet
weight)
Content
(mmol)
% of total
body
magnesium
Serum 3.0 0.85 2.6 0.3
Red blood cells 2.0 2.5 5.0 0.5
Soft tissue 22.7 8.5 193.0 19.3
Muscle 30.0 9.0 270.0 27.0
Bone 12.3 43.2 530.1 52.9
Tot al 70 .0 64 .0 5 100 0.7 1 00 .0
Fig. 2. Hydroxyapatite crystal unit. Enamel apatite contains the lowest
concentrations of carbonate and magnesium ions, and is rich in fluoride
F. Dentin and bone have the highest levels of carbonate and magnesium
ions, but have low fluoride content. Fluoride decreases solubility and in-
creases chemical stability, carbonate, chloride and especially magnesium
all increase solubility of the otherwise very insoluble mineral. Chemically
the mineral comprises a highly substituted carbonated calcium hydroxya-
patite (HAP). In the absence of exact compositional analysis the biogenic
forms of this mineral are collectively alluded to as ‘‘bioapatite’’. Ca, calcium;
Na, sodium; Mg, magnesium; Sr, strontium; OH, hydroxide; Cl, chloride; F,
fluoride; PO
4
,HPO
4
, phosphate; CO
3
, carbonate.
Fig. 3. Total serum magnesium is present in three different states. Because
of different measurement methods, results published for each state of
serum magnesium vary considerably. Therefore, a range for every state is
provided [7,21,2324]. For additional data, please see also Tabl es 1 and 2
in the article by Cunningham et al.[28] in this supplement.
Table 3. Magnesium has numerous functions in the body, for example,
serving as a cofactor in enzymatic reactions
a
. Reprinted from [8], with
permission.
Enzyme function
Enzyme substrate (ATP-Mg, GTP-Mg)
Kinases B
Hexokinase
Creatine kinase
Protein kinase
ATPases or GTPases
Na
1
/K
1
-ATPase
Ca
21
-ATPase
Cyclases
Adenylate cyclase
Guanylate cyclase
Direct enzyme activation
Phosphofructokinase
Creatine kinase
5-Phosphoribosyl-pyrophosphate synthetase
Adenylate cyclase
Na
1
/K
1
-ATPase
Membrane function
Cell adhesion
Transmembrane electrolyte flux
Calcium antagonist
Muscle contraction/relaxation
Neurotransmitter release
Action potential conduction in nodal tissue
Structural function
Proteins
Polyribosomes
Nucleic acids
Multiple enzyme complexes
Mitochondria
a
Magnesium is also necessary for structural function of proteins, nucleic
acids or mitochondria. Moreover, it is a natural calcium antagonist [8].
ATP, adenosine triphosphate; GTP, guanosine triphosphate; K, potassium;
Mg, magnesium; Na, sodium; Ca, calcium.
Magnesium basics i5
at RWTH Aachen, on March 4, 2012http://ckj.oxfordjournals.org/Downloaded from
and is important for cell adhesion and transmembrane
transport including transport of potassium and calcium
ions. It also maintains the conformation of nucleic acids
and is essential for the structural function of proteins and
mitochondria.
It has long been suspected that magnesium may have a
role in insulin secretion owing to the altered insulin secre-
tion and sensitivity observed in magnesium-deficient ani-
mals [31]. Epidemiological studies have shown a high
prevalence of hypomagnesaemia and lower intracellular
magnesium concentrations in diabetics. Benefits of mag-
nesium supplementation on the metabolic profile of dia-
betics have been observed in some, but not all, clinical
trials, and so larger prospective studies are needed to de-
termine if dietary magnesium supplementation is associ-
ated with beneficial effects in this group [32].
Recent epidemiological studies have suggested that a
relatively young gestational age is associated with mag-
nesium deficiency during pregnancy, which not only indu-
ces maternal and foetal nutritional problems but also
leads to other consequences that might affect the off-
spring throughout life [33].
There is also evidence that magnesium and calcium
compete with one another for the same binding sites on
plasma protein molecules [13,34]. It was shown that mag-
nesium antagonizes calcium-dependent release of acetyl-
choline at motor endplates [6]. Thus, magnesium may be
considered a natural ‘calcium antagonist’. While calcium is
a powerful ‘death trigger’ [35], magnesium is not [34]:
magnesium inhibits calcium-induced cell death [36]. It is
anti-apoptotic in mitochondrial permeability transition
and antagonizes calcium-overload-triggered apoptosis.
Magnesium is important in health and disease, as will be
discussed in more detail in this supplement in the article by
Geiger and Wanner [37].
Regulation of magnesium influx and efflux
There is considerable variation in the plasma/tissue ex-
change of magnesium between various organs of an ani-
mal and also between animal species [5]. These
observations indicate that various cell types handle mag-
nesium quite differently, which is again different from cal-
cium [10]. Myocardium, kidney parenchyma, fat tissue,
skeletal muscle, brain tissue and lymphocytes exchange
intracellular and extracellular magnesium at different
rates. In mammalian heart, kidney and adipocytes, total
intracellular magnesium is able to exchange with plasma
magnesium within 3–4 h [3842]. In man, equilibrium for
magnesium among most tissue compartments is reached
very slowly, if at all [17]. About 85% of the whole body
magnesium, measured as
[28]
Mg is either non-exchange-
able or exchanges very slowly with a roughly estimated
biological half-life of ~1000 h [43].
Magnesium consumption
Humans need to consume magnesium regularly to prevent
magnesium deficiency, but as the recommended daily al-
lowance for magnesium varies, it is difficult to define ac-
curately what the exact optimal intake should be. Values of
"300 mg are usually reported with adjusted dosages for
age, sex and nutritional status. The Institute of Medicine
recommends 310–360 mg and 400–420 mg for adult
women and men, respectively. Other recommendations
in the literature suggest a lower daily minimum intake of
350 mg for men and 280–300 mg magnesium for women
(355 mg during pregnancy and lactation) [2,7,10,18].
While drinking water accounts for ~10% of daily magne-
sium intake [44], chlorophyll (and thus green vegetables) is
the major source of magnesium. Nuts, seeds and unpro-
cessed cereals are also rich in magnesium [15]. Legumes,
fruit, meat and fish have an intermediate magnesium con-
centration. Low magnesium concentrations are found in
dairy products [7]. It is noteworthy that processed foods
have a much lower magnesium content than unrefined
grain products [7] and that dietary intake of magnesium
in the western world is decreasing owing to the consump-
tion of processed food [45]. With the omnipresence of pro-
cessed foods, boiling and consumption of de-mineralized
soft water, most industrialized countries are deprived of
their natural magnesium supply. On the other hand, mag-
nesium supplements are very popular food supplements,
especially in the physically active.
Magnesium absorption and excretion
Magnesium homeostasis is maintained by the intestine,
the bone and the kidneys. Magnesium—just like calcium—
is absorbed in the gut and stored in bone mineral, and
excess magnesium is excreted by the kidneys and the
faeces (Figure 4). Magnesium is mainly absorbed in the
small intestine [21,15,46], although some is also taken
up via the large intestine [7,10,47]. Two transport sys-
tems for magnesium in the gut are known (as discussed
in the article by de Baaij et al. [48] in this supplement).
The majority of magnesium is absorbed in the small in-
testine by a passive paracellular mechanism, which is
driven by an electrochemical gradient and solvent drag.
A minor, yet important, regulatory fraction of magnesium
is transported via the transcellular transporter transient
receptor potential channel melastatin member (TRPM) 6
and TRPM7—members of the long transient receptor po-
tential channel family—which also play an important role
in intestinal calcium absorption [21]. Of the total dietary
magnesium consumed, only about 24–76% is absorbed in
the gut and the rest is eliminated in the faeces [46]. It is
Fig. 4. Magnesium balance. Values as indicated based on [7]. The conver-
sion factor from milligrams to millimole is 0.04113.
i6 W. Jahnen-Dechent and M. Ketteler
at RWTH Aachen, on March 4, 2012http://ckj.oxfordjournals.org/Downloaded from
noteworthy that intestinal absorption is not directly pro-
portional to magnesium intake but is dependent mainly
on magnesium status. The lower the magnesium level,
the more of this element is absorbed in the gut, thus
relative magnesium absorption is high when intake is low
and vice versa. When intestinal magnesium concentration
is low, active transcellular transport prevails, primarily in the
distal small intestine and the colon (for details, see de Baaij
et al. [48] in this supplement).
The kidneys are crucial in magnesium homeostasis [18,
4951] as serum magnesium concentration is primarily
controlled by its excretion in urine [7]. Magnesium excre-
tion follows a circadian rhythm, with maximal excretion
occurring at night [15]. Under physiological conditions,
~2400 mg of magnesium in plasma is filtered by the glo-
meruli. Of the filtered load, ~95% is immediately reab-
sorbed and only 3–5% is excreted in the urine [10,52],
i.e. ~100 mg. It is noteworthy that magnesium transport
differs from that of the most other ions since the major re-
absorption site is not the proximal tubule, but the thick
ascending limb of the loop of Henle. There, 60–70% of
magnesium is reabsorbed, and another small percentage
(~10%) is absorbed in the distal tubules. The kidneys, how-
ever, may lower or increase magnesium excretion and re-
absorption within a sizeable range: renal excretion of the
filtered load may vary from 0.5 to 70%. On one hand, the
kidney is able to conserve magnesium during magnesium
deprivation by reducing its excretion; on the other hand,
magnesium might also be rapidly excreted in cases of ex-
cess intake [18]. While reabsorption mainly depends on
magnesium levels in plasma, hormones play only a minor
role (e.g. parathyroid hormone, anti-diuretic hormone, glu-
cagon, calcitonin), with oestrogen being an exception to
this rule.
Assessment of magnesium status
Serum magnesium concentration
To date, three major approaches are available for clinical
testing (Table 4). The most common test for the evaluation
of magnesium levels and magnesium status in patients is
serum magnesium concentration [21,56], which is valua-
ble in clinical medicine, especially for rapid assessment of
acute changes in magnesium status [17]. However, serum
magnesium concentration does not correlate with tissue
pools, with the exception of interstitial fluid and bone. It
also does not reflect total body magnesium levels [17,57].
Only 1% of total body magnesium is present in extracel-
lular fluids, and only 0.3% of total body magnesium is
found in serum, and so serum magnesium concentrations
[22] are poor predictors of intracellular/total body magne-
sium content [7]. This situation is comparable to assessing
total body calcium by measuring serum calcium, which,
too, does not adequately represent total body content.
As with many reference values, laboratory parameters will
also vary from laboratory to laboratory resulting in slightly
varying ranges for the ‘healthy’ populations evaluated.
What is considered the ‘normal level’ might actually be
slightly too low, representing a mild magnesium deficit
present in the normal population [17].
In addition, there are individuals—in particular those
with a subtle chronic magnesium deficiency—whose se-
rum magnesium levels are within the reference range
but who still may have a deficit in total body magnesium.
And vice versa: some people—though very few—have low
serum magnesium levels but a physiological magnesium
body content [17]. Moreover, serum magnesium might be
higher in vegetarians and vegans than in those with om-
nivorous diets. The same applies to levels after short peri-
ods of maximal exercise as lower serum levels are
observed after endurance exercises [58,59] and also dur-
ing the third trimester of pregnancy. There is also intra-
individual variability [60]. Moreover, measurements are
strongly affected by haemolysis (and therefore by a delay
in separating blood), and by bilirubin [59].
#Magnesium is essential for man and has to be
consumed regularly and in sufficient amount to
prevent deficiency.
#It is a cofactor in more than 300 enzymatic re-
actions needed for the structural function of pro-
teins, nucleic acids and mitochondria.
#Absorption is complex, depending on the individ-
ual’s magnesium status, and excretion is con-
trolled primarily by the kidneys.
Table 4. Magnesium assessment [7, 21]
Magnesium in:
Serum
Red blood cells
a
Leucocytes
b
Muscle
c
Metabolic assessment via:
Balance studies
Isotopic analyses
Renal excretion of magnesium
Retention of magnesium, following acute administration
Free magnesium levels with:
Fluorescent probes
d
Ion-selective electrodes
e
Nuclear magnetic resonance spectroscopy
f,g
Metallochrome dyes
a
Red blood cell magnesium concentration does not seem to correlate well
with total body magnesium status [53].
b
Magnesium content of mononuclear cells may be a better predictor of
skeletal and cardiac muscle magnesium content [54].
c
Muscle is an appropriate tissue for the assessment of magnesium status
[55] but it is an invasive and expensive procedure requiring special expertise.
d
Intracellular free magnesium concentration can be determined by using
fluorescent probes [10]. Application of fluorescent dyes, however, is limited
because the major fluorescent dye for magnesium (mag-fura 2) has a higher
affinity for calcium than for magnesium.
e
Ion-specific microelectrodes can be used to measure the internal free ion
concentration of cells and organelles. Major advantages are that readings
can be made over long time spans. In contrast to dyes, very little extra ion
buffering capacity has to be added to the cells, and direct measurement of
the ion flux across the membrane of a cell is possible with every ion passin g
across the membrane contributing to the result. Nonetheless, ion-selective
electrodes for magnesium are not entirely selec tive for ionized magnesium.
A correction is applied based on the ionized calcium concentration [10].
f
Total magnesium content of a biological sample can be determined by
using flame atomic absorption spectroscopy (AAS). However, this technique
is destructive and, for optimal accuracy, sample volume has to add up to ~2
mL with a concentration ranging from 0.1 to 0.4 lmol/L. With this techni-
que, only content, not uptake, can be quantified.
g
Nuclear magnetic resonance may be used to measure intracellular free
magnesium concentration [10].
Magnesium basics i7
at RWTH Aachen, on March 4, 2012http://ckj.oxfordjournals.org/Downloaded from
In healthy individuals, magnesium serum concentration
is closely maintained within the physiological range [13,
15,18]. This reference range is 0.65–1.05 mmol/L for total
magnesium concentrations in adult blood serum [61] and
0.55–0.75 mmol/L for ionized magnesium [62]. According
to Graham et al. [46], blood plasma concentration in
healthy individuals is similar to serum, ranging from 0.7
to 1.0 mmol/L.
Magnesium concentration in RBCs is generally higher
than its concentration in serum [46] (i.e. 1.65–2.65
mmol/L) [61]. The magnesium concentration is even
higher in ‘young’ RBCs [13], which might be particularly
relevant in patients receiving erythropoietin. Thus, when
measuring magnesium serum levels, it is important to
avoid haemolysis to prevent misinterpretation [17,22].
Although some limitations may apply, serum magne-
sium concentration is still used as the standard for evalu-
ating magnesium status in patients [21]. It has proven
helpful in detecting rapid extracellular changes. In addi-
tion, measuring serum magnesium is feasible and inex-
pensive [As an example: Mg in serum (photometric
assessment/AAS)—Germany (Synlab, Augsburg): EBM
32248 (EBM ¼einheitlicher Bewertungsmaßstab fu
¨rA
¨rzte,
kassena
¨rztliche Abrechnung; valuation standard) ¼1.40 V;
GOA
¨3621 1.00 (GOA
¨¼Gebu
¨hrenordnung fu
¨rA
¨rzte, pri-
vate; scale of charges for physicians) ¼2.33 V; Denmark
(GPs laboratory, Copenhagen): 87.50 DDK ¼11.66 V; France
(Biomnis, Ivry-sur Seine) ¼1.89 V] and should become
more common in clinical routine.
Twenty-four-hour excretion in urine
Another approach for the assessment of magnesium sta-
tus is urinary magnesium excretion. This test is cumber-
some, especially in the elderly, since it requires at least a
reliable and complete 24-h time frame [54]. As a circadian
rhythm underlies renal magnesium excretion, it is impor-
tant to collect a 24-h urine specimen to assess magnesium
excretion and absorption accurately. This test is particu-
larly valuable for assessing magnesium wasting by the
kidneys owing to medication or patients’ physiological sta-
tus [7]. The results will provide aetiological information:
while a high urinary excretion indicates renal wasting of
magnesium, a low value suggests an inadequate intake or
absorption [7].
Magnesium retention test—‘loading test’ A further re-
finement is the magnesium retention test. This ‘loading
test’ may serve for identification of patients with hypo-
magnesaemic and normomagnesaemic magnesium defi-
ciencies. Retention of magnesium following acute oral or
parenteral administration is used to assess magnesium
absorption, chronic loss and status. Changes in serum
magnesium concentration and excretion following an
oral magnesium load reflect intestinal magnesium ab-
sorption [7,63]. Magnesium retained during this test is
retained in bone. Thus, the lower the bone magnesium
content the higher the magnesium retention in this test
[64]. The percentage of magnesium retained is increased
in cases of magnesium deficiency and is inversely corre-
lated with the concentration of magnesium in bone [65,
66]. This test quantifies the major exchangeable pool of
magnesium, providing a more sensitive index of magne-
sium deficiency than simply measuring serum magne-
sium concentration. A urinary excretion of >60–70% of
the magnesium load suggests that magnesium depletion
is unlikely. Standardization of this test, however, is lacking
[22].
Isotopic analysis of magnesium
Magnesium exists in three different isotopes: 78.7% occurs
as
[24]
Mg, 10.1% as
[25]
Mg and 11.2% as
[26]
Mg [5].
[28]
Mg is
radioactive and was made available commercially for sci-
entific use in the 1950s to the 1970s. Radioactive tracer
elements in ion uptake assays allow the calculation of the
initial change in the ion content of the cells.
[28]
Mg decays
by emission of high-energy beta or gamma particles that
can be measured using a scintillation counter. However,
the radioactive half-life of the most stable radioactive
magnesium isotope—
[28]
Mg—is only 21 h, restricting its
use.
[26]
Mg was used to assess absorption of magnesium
from the gastrointestinal tract, presenting nutritional and
analytical challenges. Although studies with isotopes of
magnesium can provide important information, they are
limited to research [7]. Surrogates for magnesium (i.e.
Mn
21
, Ni
21
and Co
21
) have been used [5]. They were used
to mimic the properties of magnesium in some enzymatic
reactions, and radioactive forms of these elements were
successfully employed in cation transport studies. The
most common surrogate is Mn
21
that can replace magne-
sium in the majority of enzymes where ATP-Mg is used as a
substrate [5].
Pathophysiology
Hypomagnesaemia
The definition of magnesium deficiency seems simpler
than it is, primarily because accurate clinical tests for the
assessment of magnesium status are still lacking. Evalua-
tion of serum magnesium concentration and collection of
a 24-h urine specimen for magnesium excretion are at
present the most important laboratory tests for the diag-
nosis of hypomagnesaemia. The next step would be to
perform a magnesium retention test [7].
In the literature, patients with serum magnesium con-
centrations $0.61 mmol/L (1.5 mg/dL) [6769] and $0.75
mmol/L, respectively, were considered hypomagnesaemic
[70,71].
Hypomagnesaemia is common in hospitalized patients,
with a prevalence ranging from 9 to 65% [67,6972]. A
particularly high incidence of hypomagnesaemia is ob-
served in intensive care units. Furthermore, a significant
#Assessment of total serum magnesium concen-
tration is the most practicable and inexpensive
approach for the detection of acute changes in
magnesium status.
#However, one should bear in mind that serum
magnesium concentration does not reflect the
patient’s magnesium status accurately as it does
not correlate well with total magnesium body
content.
i8 W. Jahnen-Dechent and M. Ketteler
at RWTH Aachen, on March 4, 2012http://ckj.oxfordjournals.org/Downloaded from
association has been reported between hypomagnesae-
mia and esophageal surgery [70]. In these severely ill pa-
tients, nutritional magnesium intake was probably
insufficient. Certain drugs have been associated with mag-
nesium wasting (although the relationship between these
factors remains unclear), putting the afflicted patients at
an increased risk for acute hypomagnesaemia. Such medi-
cations include aminoglycosides, cisplatin, digoxin, furose-
mide, amphotericin B and cyclosporine A [67,70](Table 5).
Moreover, it was observed that in patients with severe
hypomagnesaemia, mortality rates increase [67,70].
Therefore, assessment of magnesium status is advised,
particularly inthose who are critically ill. When hypomagne-
saemia is detected, one should address—if identifiable—the
underlying pathology to reverse the depleted status [73].
Hypomagnesaemia has been linked to poor condition
(malignant tumours, cirrhosis or cerebrovascular disease)
[70] and a number of other ailments. Magnesium deficien-
cies might stem from reduced intake caused by poor nu-
trition or parenteral infusions lacking magnesium, from
reduced absorption and increased gastrointestinal loss,
such as in chronic diarrhoea, malabsorption or bowel re-
section/bypass [68]. Deficiencies might also be triggered
by increased magnesium excretion in some medical con-
ditions such as diabetes mellitus, renal tubular disorders,
hypercalcaemia, hyperthyroidism or aldosteronism or in the
course of excessive lactation or use of diuretics (Table 5).
Compartmental redistribution of magnesium in illnesses
such as acute pancreatitis might be another cause of
acute hypomagnesaemia [7]. In addition, several in-
herited forms of renal hypomagnesaemia exist [88].
These genetic changes led to the detection of various
transporters (see de Baaij et al. [48] in this supplement,
for further details).
Chronic hypomagnesaemia
Diagnosis of chronic hypomagnesaemia is difficult as there
may be only a slightly negative magnesium balance over
time. There is equilibrium among certain tissue pools, and
serum concentration is balanced by magnesium from
bone. Thus, there are individuals with a serum magnesium
concentration within the reference interval who have a
total body deficit for magnesium. Magnesium levels in se-
rum and 24-h urine samples may be normal, and so pa-
renteral administration of magnesium with assessment of
retention should be considered if in doubt [7]. Chronic la-
tent magnesium deficiency has been linked to atheroscle-
rosis, myocardial infarction, hypertension (see also Geiger
and Wanner [37] in this supplement.), malignant tumours,
kidney stones, alteration in blood lipids, premenstrual syn-
drome and psychiatric disorders.
Clinical signs of hypomagnesaemia
Clinical signs of hypo- and hypermagnesaemia overlap
often and are rather non-specific. Manifestations of hypo-
magnasaemia might include tremor, agitation, muscle
fasciculation, depression, cardiac arrhythmia and hypoka-
laemia [6,10,67](Table 6). Early signs of magnesium de-
ficiency include loss of appetite, nausea, vomiting, fatigue
and weakness [67]. As magnesium deficiency worsens,
numbness, tingling, muscle contractions, cramps, seizures,
sudden changes in behaviour caused by excessive electri-
cal activity in the brain, personality changes [67], abnor-
mal heart beat and coronary spasms might occur. Severe
hypomagnesaemia is usually accompanied by other im-
balances of electrolytes such as low levels of calcium
and potassium in the blood (for mechanisms, see de Baaij
et al. [48] in this supplement). However, even in patients
with severe hypomagnesaemia, clinical signs associated
with magnesium deficiency may be absent [7]. In addition,
Table 5. Settings in which symptomatic hypomagnesaemia might occur
Decreased dietary intake:
Malnutrition
Parenteral infusions without magnesium
Gastrointestinal malabsorption and loss [6]:
Severe or prolonged chronic diarrhoea [6–8]
Increased renal loss [6]:
Congenital or acquired tubular defects (see de Baaij et al. [48]
in this supplement)
Drug induced:
Loop diuretics
a
[7, 74]
Aminoglycosides [7, 8, 70, 75]
Amphotericin B [8, 76]
Cyclosporine [8, 77] and tacrolimus [78]
Cisplatin [8, 79]
Cetuximab [80]
Omeprazole [81]
Pentamidine [8, 82]
Foscarnet [83]
Endocrine causes:
Primary and secondary hyperaldosteronism [8, 84]
Hungry bone syndrome, e.g. after surgery of primary
hyperparathyroidism
b
[7, 8]
Syndrome of inappropriate anti-diuretic hormone hypersecretion
Diabetes mellitus [6, 8]
Other causes:
Stress
Chronic alcoholism
c
[7, 8]
Excessive lactation, heat, prolonged exercise [6]
Severe burns [6, 85]
Cardiopulmonary bypass surgery [86]
Iatrogenic [6]
a
Loop diuretics such as furosemide, torasemide, ethacrynic acid, bumetha-
nide and piretanide cause an increased urinary excretion [74]. Thiazide
diuretics, acting on the early distal tubule, might lead to magnesium loss
only in the long run [87]. In contrast, potassium-sparing diuretics, such as
triamterene and amiloride acting on the late distal tubule, contribute to
magnesium conservation by the kidneys. Osmotic agents such as mannitol
or glucose hamper tubular re-absorption and augment magnesium excre-
tion [7, 52].
b
Hypomagnesaemia—due to deposition of magnesium in the calcium- and
magnesium-depleted bone—occurs in one third of the patients after sur-
gical correction of primary hyperparathyroidism [7].
c
It was observed that chronic alcohol consumption goes along with a sig-
nificant increase of urinary magnesium excretion and a reduced muscle
magnesium content. Thus, empiric use of magnesium replacement therapy
was suggested as part of the therapeutic alcohol withdrawal syndrome
regimen [7].
Table 6. Clinical and laboratory manifestations of hypomagnesaemia.
Reprinted from [7], with permission from Elsevier
Neuromuscular Cardiac
Central nervous
system Metabolic
Weakness Arrhythmias Depression Hypokalaemia
Tremor ECG changes Agitation Hypocalcaemia
Muscle fasciculation Psychosis
Positive Chvostek’s
sign
b
Nystagmus
Positive Trousseau’s
sign
c
Seizures
Dysphagia
a
ECG, electrocardiogram.
b
Sign of tetany, an abnormal reaction (i.e. facial twitching) seen as a reac-
tion to the tapping of the facial nerve.
c
Characteristic spasm of muscles of the hand and forearm seen following
occlusion of the brachial artery.
Magnesium basics i9
at RWTH Aachen, on March 4, 2012http://ckj.oxfordjournals.org/Downloaded from
there seems to be a greater likelihood of clinical symptoms
with a rapid decrease in serum magnesium concentration
compared with a more gradual change. Therefore, physi-
cians should not wait for clinical signs to occur before
checking serum magnesium levels [7].
Hypermagnesaemia
As the kidneys play a crucial role in magnesium homeo-
stasis, in advanced chronic kidney disease, the compensa-
tory mechanisms start to become inadequate and
hypermagnesaemia may develop (see Cunningham et al
[28] in this supplement). Symptomatic hypermagnesae-
mia may be caused by excessive oral administration of
magnesium salts or magnesium-containing drugs such
as some laxatives [89] and antacids [14], particularly when
used in combination in the elderly and when renal function
declines [8,67,9094]. In addition, hypermagnesaemia
may be iatrogenic, when magnesium sulphate is given as
an infusion for the treatment of seizure prophylaxis in
eclampsia [67,95] or erroneously in high doses for mag-
nesium supplementation [96,97].
Prevalence of—mostly undiagnosed—hypermagnesaemia
in hospitalized patients is reported, varying from 5.7% [98]
to 7.9% [67] and 9.3% [69]. In intensive care patients, the
prevalence of total hypermagnesaemia was reported as
being 13.5%, whereas ionized hypermagnesaemia was
23.6% [99]. These studies did not specify whether hyper-
magnesaemia in hospitalized patients was a pathological
consequence of severe disease, or if it was iatrogenic, per-
haps reflecting excessive magnesium supplementation in
intensive care.
Case reports exist of pre-term babies with extreme hy-
permagnesaemia—magnesium levels of 17.5 mmol/L
[100] and 21.5 and 22.5 mmol/L [97]—which, in one case,
was the result of a malfunctioning total parenteral nutri-
tion mixing device. All three infants survived. There are
other reports about affected neonates whose mothers
had gestational toxicosis and who had been treated with
magnesium sulphate because of eclamptic convulsion [7].
Excessive magnesium ingestion and intoxication was also
reported in association with drowning in the Dead Sea. The
average serum magnesium concentration in 48 adults
who ‘nearly drowned’ in the Dead Sea was 3.16 mmol/L,
with one patient recorded at 13.57 mmol/L [101103].
Clinical signs of hypermagnesaemia
Serum magnesium concentrations, as reported in the lit-
erature, vary widely among patients with similar signs and
symptoms. In the beginning, no immediate clinical signs
may be present and hypermagnesaemia might stay unde-
tected for sometime [67]. For example, increased magne-
sium concentrations (>1.07 mmol/L) were found in sera
from 7.9% of 6252 patients, but no description of symp-
toms was noted in 80% of clinical charts, also not in pa-
tients with values >1.6 mmol/L (0.8%) [67]. Moderately
elevated serum magnesium levels may be associated with
hypotension, cutaneous flushing, nausea and vomiting,
but these symptoms mostly occur only upon infusion of
magnesium sulphate. At higher concentrations, magne-
sium might lead to neuromuscular dysfunction, ranging
from drowsiness to respiratory depression, hypotonia, are-
flexia and coma in severe cases. Cardiac effects of hyper-
magnesaemia may include bradycardia; uncharacteristic
electrocardiogram findings such as prolonged PR, QRS
and QT intervals, complete heart block, atrial fibrillation
and asystole. However, these findings are neither diagnostic
nor specific for this metabolic abnormality [100](Table 7).
Absence of deep tendon reflexes might help diagnose
excess magnesium levels [7]. Deep tendon reflexes may be
diminished at serum magnesium concentrations >2.5
mmol/L and will vanish when levels exceed 5 mmol/L.
At these levels, severe muscle weakness has also been
observed [21](Table 7).
Treatment of hypo- and hypermagnesaemia
In cases of mild hypomagnesaemia in otherwise healthy
individuals, oral magnesium administration is used suc-
cessfully [68]. Acute and chronic oral magnesium supple-
mentation has been described as well tolerated with a
good safety profile [104,105]. Intravenous administration
of magnesium, mostly as magnesium sulphate, should be
used when an immediate correction is mandatory as in
patients with ventricular arrhythmia and severe hypomag-
nesaemia [106].
Treatment of patients with symptomatic hypermagne-
saemia includes discontinuation of magnesium adminis-
tration, use of supportive therapy and administration of
calcium gluconate [6,107]. Treatment of severe, sympto-
matic hypermagnesaemia may require haemodialysis [7].
Conclusions
The chemistry of magnesium is unique among cations of
biological relevance. Magnesium is essential for man and is
required in relatively large amounts. Magnesium is a co-
factor in >300 enzymatic reactions and thus it is essential
for many crucial physiological functions, such as heart
rhythm, vascular tone, nerve function and muscle contrac-
tion and relaxation. Magnesium is also needed for bone
formation and can also be referred to as a natural ‘calcium
antagonist’. However, hypomagnesaemia is rather com-
mon, in particular, in hospitalized patients. Moreover, as
the intake of refined foods increases—as appears to be
the case in developed countries—magnesium deficiency
will most likely evolve into a more common disorder. None-
theless, total serum magnesium is rarely measured in clin-
ical practice. Despite some limitations, the assessment of
serum magnesium concentration is inexpensive and easy
to employ and provides important information about
magnesium status in patients.
#Mild hypo- and hypermagnesaemia are quite
common, especially in hospitalized patients,
and may not be associated with clinical symp-
toms.
#Severe hypo- and hypermagnesaemia show par-
tially overlapping symptoms, making diagnosis
difficult without assessment of serum magne-
sium concentration.
i10 W. Jahnen-Dechent and M. Ketteler
at RWTH Aachen, on March 4, 2012http://ckj.oxfordjournals.org/Downloaded from
Table 7. Clinical manifestations of hypermagnaesemia
a
Serum Mg (mmol/L)
Symptoms
Neurological Circulatory–respiratory–gastrointestinal ECG Comments
2.1–2.4 Paralytic ileus [110] Bradycardia [111] Both single case reports, one Patient suffering
from chronic renal insufficiency (creatinine
clearance 13 ml/min) [111], iatrogenic [111]
2.5–4.0 Deep tendon reflexes depressed
[107, 108, 109], muscle weakness,
slurred speech, lethargy [91]
Hypotension, nausea, flushing, decreased
uterine tone upon magnesium infusion [109];
gastrointestinal paralysis [110]
Tac hy cardi a, T- wave ab norma lit ie s;
prolonged QT-time [91]
Target level for treatment of eclampsia is
2.5-4.0 mmol/L. [22, 108, 109, 112, 113]. However,
serum Mg values are measured infrequently.
Even in patients treated with MgSO
4
, decisions
are based on clinical signs such as depressed
deep-tendon reflexes [27]. Case reports [91, 110],
renal insufficiency [110]
3.7–4.9 Confusion [114], loss of deep tendon
reflexes [109], neuromuscular blockade,
quadriparesis [115]
Hypotension [114] Single case reports [114, 115], renal failure,
PD treatment [115], review [109]
5.0–6.95 Lethargy [94, 116], slurred speech,
profound muscle weakness [90]
Hypotension [94, 116], increased respiratory
rate
b
[94, 109]; respiratory arrest [95]
Atrial fibrillation [94]; QT prolongation
[92, 116] sinus tachycardia, 1st degree
AV-block, bradycardia [92]
Single case reports [92, 95, 116], case reports
and reviews [90, 94], review [109]
Up to $7.65 and 7.3 Paralysis of the limbs [117] No respiratory arrest, slight decrease of blood
pressure [117]
Sinus arrhythmia, slight alterations in
ventricular action (T-wave, ST, R
abnormalities, prolonged PR interval)
[117]
Clinical investigation in two individuals in an
experimental setting during magnesium
sulphate infusion [117]
>8.9–10.65 ‘Coma’ [118, 119], pseudocomatose state,
central brain-stem herniation syndrome,
non-fatal neuromuscular blockade
Profound hypotension, cardiopulmonary
non-fatal arrest [118, 120], cardiovascular
collapse at 25 mg/dL (10.3 mmol) [109]
Prolonged QT interval, bradycardia
[120]
Case reports [118–121], review [109]
Up to 13. 5 [102];
16.9 [122]; 17.8 [100];
21.5 and 22.5 [97]
Respiratory depression, apnoea [97, 100],
cardiopulmonary arrest [122]
Non-fatal refractory bradycardia [97] Case reports, newborns [97, 100], case report,
child [122], description of Dead Sea poisoning in
48 patients with different degrees of
intoxication, the most dangerous combination
occurred when serum calcium concentration
was also high [102]
a
The table demonstrates a certain difficulty to link clinically distinct symptoms to specific serum magnesium levels. However, neurological symptoms, such as depression/loss of deep tendon reflexes, unequivocally
occur at serum levels greater than 3.7 to 4.0 mmol/L.
b
Symptom also used for monitoring purposes in eclampsia [109]
AV, atrio-ventricular; Mg, magnesium; MgSO
4
, magnesium sulphate; PD, peritoneal dialysis.
Magnesium basics i11
at RWTH Aachen, on March 4, 2012http://ckj.oxfordjournals.org/Downloaded from
Acknowledgements. Ronald J. Elin, Department of Pathology and
Laboratory Medicine, School of Medicine, University of Louisville,
Louisville, KY USA, thoroughly investigated the basics of magne-
sium and published numerous scientific papers on this topic. As
basic knowledge comes from these publications, we often quoted
his work. In addition, the authors thank Martina Sintzel, Zu
¨rich,
Switzerland and Yvette C. Zwick, Munich, Germany for providing
writing and editorial assistance and Richard Clark, Dunchurch, UK
for his comments on the final manuscript, all on behalf of Fresenius
Medical Care Deutschland GmbH. Fresenius also made an unre-
stricted educational grant to meet the cost of preparing this
article. These declarations are in line with the European Medical
Writers’ Association guidelines.
Conflict of interest statement. W.J.-D. has received speakers’ hon-
oraria from Amgen, Genzyme, Fresenius and Ko
¨hler-Chemie. M.K.
has received speaker’s and/or consultancy honoraria from Amgen,
Abbott, Fresenius, Genzyme, Medice and Shire and research sup-
port from Abbott and Amgen.
References
1. Cotton FA, Wilkinson G. Anorganische Chemie. Weilheim,
Germany: Chemie GmbH, 1967
2. Weast RC. Handbook of Chemistry and Physics. Boca Raton,
FL: CRC Press; 1987
3. Hollemann AF, Wiberg E. Lehrbuch der anorganischen
Chemie. Berlin, Germany: De Gruyter; 1964
4. Bodaker I, Sharon I, Suzuki MT et al. Comparative community
genomics in the Dead Sea: an increasingly extreme environ-
ment. ISME J 2010; 4: 399–407
5. Maguire ME, Cowan JA. Magnesium chemistry and biochem-
istry. Biometals 2002; 15: 203–210
6. Wacker W. Magnesium and Man. Cambridge, MA: Havard Uni-
versity Press; 1980; 1–184
7. Elin RJ. Magnesium metabolism in health and disease. Dis
Mon 1988; 34: 161–218
8. Swaminathan R. Magnesium metabolism and its disorders.
Clin Biochem Rev 2003; 24: 47–66
9. Feillet-Coudray C, Coudray C, Gueux E et al. A new in vitro
blood load test using a magnesium stable isotope for assess-
ment of magnesium status. J Nutr 2003; 133: 1220–1223
10. Saris NE, Mervaala E, Karppanen H et al. An update on phys-
iological, clinical and analytical aspects. Clin Chim Acta 2000;
294: 1–26
11. Grubbs RD, Maguire ME. Magnesium as a regulatory cation:
criteria and evaluation. Magnesium 1987; 6: 113–127
12. Maguire ME. Magnesium: a regulated and regulatory cation.
Met Ions Biol Syst 1990; 26: 135–153
13. Walser M. Magnesium metabolism. Ergeb Physiol 1967; 59:
185–296
14. Aikawa JK. Magnesium: Its Biological Significance. Boca Ra-
ton, FL: CRC Press; 1981
15. Fox C, Ramsoomair D, Carter C. Magnesium: its proven and
potential clinical significance. South Med J 2001; 94:
1195–1201
16. Lewellen TK, Nelp WB, Murano R et al. Absolute measure-
ment of total-body calcium by the Ar-37 method-preliminary
results: concise communication. J Nucl Med 1977; 18:
929–932
17. Elin RJ. Assessment of magnesium status for diagnosis and
therapy. Magnes Res 2010; 23: 194–198
18. Rude R. Magnesium disorders. In: Kokko J, Tannen R (eds).
Fluids and electrolytes. Philadelphia, PA: W.B. Saunders
Company, 1996, pp. 421–445
19. Alfrey AC, Miller NL. Bone magnesium pools in uremia. J Clin
Invest 1973; 52: 3019–3027
20. Kroll MH, Elin RJ. Relationships between magnesium and
protein concentrations in serum. Clin Chem 1985; 31:
244–246
21. Touyz RM. Magnesium in clinical medicine. Front Biosci 2004;
9: 1278–1293
22. Fawcett WJ, Haxby EJ, Male DA. Magnesium: physiology and
pharmacology. Br J Anaesth 1999; 83: 302–320
23. Speich M, Bousquet B, Nicolas G. Reference values for ion-
ized, complexed, and protein-bound plasma magnesium
in men and women. Clin Chem 1981; 27: 246–248
24. Walser M. Ion association. VI. Interactions between cal-
cium, magnesium, inorganic phosphate, citrate and pro-
tein in normal human plasma. JClinInvest1961; 40:
723–730
25. Navarro-Gonzalez JF, Mora-Fernandez C, Garcia-Perez J.
Clinical implications of disordered magnesium homeostasis
in chronic renal failure and dialysis. Semin Dial 2009; 22:
37–44
26. Wills MR, Lewin MR. Plasma calcium fractions and the pro-
tein-binding of calcium in normal subjects and in patients
with hypercalcaemia and hypocalcaemia. J Clin Pathol
1971; 24: 856–866
27. Keller H. Klinisch-chemische Labordiagnostik fu
¨r die Praxis.
Stuttgart, Germany: Georg Thieme; 1991: 222
28. Cunningham J, Rodrı
´guez JM, Messa P. Magnesium in chronic
kidney disease stages 3 and 4, and in dialysis patients. Clin
Kidney J 2012; 5(Suppl 1): i39–i51
29. Shechter M, Merz CN, Paul-Labrador M et al. Oral magnesium
supplementation inhibits platelet-dependent thrombosis in
patients with coronary artery disease. Am J Cardiol 1999; 84:
152–156
30. Altura BM, Altura BT. New perspectives on the role of mag-
nesium in the pathophysiology of the cardiovascular system.
I. Clinical aspects. Magnesium 1985; 4: 226–244
31. Reis MA, Reyes FG, Saad MJ et al. Magnesium deficiency mod-
ulates the insulin signaling pathway in liver but not muscle of
rats. J Nutr 2000; 130: 133–138
32. Barbagallo M, Dominguez LJ. Magnesium metabolism in type
2 diabetes mellitus, metabolic syndrome and insulin resist-
ance. Arch Biochem Biophys 2007; 458: 40–47
33. Takaya J, Kaneko K. Small for gestational age and magne-
sium in cord blood platelets: intrauterine magnesium defi-
ciency may induce metabolic syndrome in later life. J
Pregnancy 2011; 2011: 270474
34. Hunter DR, Haworth RA, Southard JH. Relationship between
configuration, function, and permeability in calcium-treated
mitochondria. J Biol Chem 1976; 251: 5069–5077
35. Orrenius S, Zhivotovsky B, Nicotera P. Regulation of cell
death: the calcium-apoptosis link. Nat Rev Mol Cell Biol
2003; 4: 552–565
36. Reynolds JL, Joannides AJ, Skepper JN et al. Human vascular
smooth muscle cells undergo vesicle-mediated calcification
in response to changes in extracellular calcium and phos-
phate concentrations: a potential mechanism for acceler-
ated vascular calcification in ESRD. J Am Soc Nephrol 2004;
15: 2857–2867
37. Geiger H, Wanner C. Magnesium in disease. Clin Kidney J
2012; 5(Suppl 1): i25–i38
38. Elliott DA, Rizack MA. Epinephrine and adrenocorticotropic
hormone-stimulated magnesium accumulation in adipo-
cytes and their plasma membranes. J Biol Chem 1974; 249:
3985–3990
39. Page E, Polimeni PI. Magnesium exchange in rat ventricle.
J Physiol 1972; 224: 121–139
40. Polimeni PI, Page E. Magnesium in heart muscle. Circ Res
1973; 33: 367–374
41. Rogers T, Mahan P. Exchange of radioactive magnesium in
the rat. Proc Soc Exp Biol Med 1959; 100: 235–239
42. Rogers T. Distribution of Magnesium in the Rat. Radioisotopes
in Animal Nutrition and Physiology. Vienna, Austria: Interna-
tional Atomic Energy Commission; 1965: 285–282
43. Avioli LV, Berman M. Mg28 kinetics in man. J Appl Physiol
1966; 21: 1688–1694
i12 W. Jahnen-Dechent and M. Ketteler
at RWTH Aachen, on March 4, 2012http://ckj.oxfordjournals.org/Downloaded from
44. Marx A, Neutra RR. Magnesium in drinking water and ische-
mic heart disease. Epidemiol Rev 1997; 19: 258–272
45. Ford ES, Mokdad AH. Dietary magnesium intake in a national
sample of US adults. J Nutr 2003; 133: 2879–2882
46. Graham L, Caesar J, Burgen A. Gastrointestinal absorption
and excretion of Mg
28
in man. Metabolism 1960; 9:
646–659
47. Kayne LH, Lee DB. Intestinal magnesium absorption. Miner
Electrolyte Metab 1993; 19: 210–217
48. de Baaij JHF, Hoenderop JGJ, Bindels RJM. Regulation of mag-
nesium balance: lessons learned from human genetic dis-
ease. Clin Kidney J 2012; 5(Suppl 1): i15–i24
49. Dirks JH. The kidney and magnesium regulation. Kidney Int
1983; 23: 771–777
50. Quamme GA, Dirks JH. The physiology of renal magnesium
handling. Ren Physiol 1986; 9: 257–269
51. Barnes BA, Cope O, Harrison T. Magnesium conservation in
the human being on a low magnesium diet. J Clin Invest
1958; 37: 430–440
52. Massry SG, Seelig MS. Hypomagnesemia and hypermagnese-
mia. Clin Nephrol 1977; 7: 147–153
53. Elin RJ, Hosseini JM, Gill JR Jr. Erythrocyte and mononuclear
blood cell magnesium concentrations are normal in hypo-
magnesemic patients with chronic renal magnesium wast-
ing. J Am Coll Nutr 1994; 13: 463–466
54. Martin BJ, Lyon TD, Walker W et al. Mononuclear blood cell
magnesium in older subjects: evaluation of its use in clinical
practice. Ann Clin Biochem 1993; 30(Pt 1): 23–27
55. Moller JB, Klaaborg KE, Alstrup P et al. Magnesium content of
the human heart. Scand J Thorac Cardiovasc Surg 1991; 25:
155–158
56. Huijgen HJ, Sanders R, van Olden RW et al. Intracellular and
extracellular blood magnesium fractions in hemodialysis pa-
tients; is the ionized fraction a measure of magnesium ex-
cess? Clin Chem 1998; 44: 639–648
57. Spiegel DM. Magnesium in chronic kidney disease: unan-
swered questions. Blood Purif 2011; 31: 172–176
58. Bardicef M, Bardicef O, Sorokin Y et al. Extracellular and
intracellular magnesium depletion in pregnancy and ges-
tational diabetes. Am J Obstet Gynecol 1995; 172:
1009–1013
59. Young DS. Effects of Preanalytical Variables on Clinical Labo-
ratory Tests. Washington, DC: AACC Press; 1997
60. Gonzalez-Revalderia J, Garcia-Bermejo S, Menchen-
Herreros A et al. Biological variation of Zn, Cu, and Mg in
serum of healthy subjects. Clin Chem 1990; 36: 2140–2141
61. Tietz NW. Clinical Guide to Laboratory Tests. Philadelphia, PA:
WB Saunders; 1990
62. Maj-Zurawska M. Clinical findings on human blood with the
KONE ISE for Mg
21
.Scand J Clin Lab Invest Suppl 1994; 217:
69–76
63. Nicar MJ, Pak CY. Oral magnesium load test for the assess-
ment of intestinal magnesium absorption. Application in
control subjects, absorptive hypercalciuria, primary hyper-
parathyroidism, and hypoparathyroidism. Miner Electrolyte
Metab 1982; 8: 44–51
64. Cohen L, Laor A. Correlation between bone magnesium con-
centration and magnesium retention in the intravenous
magnesium load test. Magnes Res 1990; 3: 271–274
65. Rude RK. Magnesium metabolism and deficiency. Endocrinol
Metab Clin North Am 1993; 22: 377–395
66. Nadler JL, Rude RK. Disorders of magnesium metabolism.
Endocrinol Metab Clin North Am 1995; 24: 623–641
67. Hashizume N, Mori M. An analysis of hypermagnesemia and
hypomagnesemia. Jpn J Med 1990; 29: 368–372
68. Guerrero-Romero F, Tamez-Perez HE, Gonzalez-Gonzalez G
et al. Oral magnesium supplementation improves insulin
sensitivity in non-diabetic subjects with insulin resistance.
A double-blind placebo-controlled randomized trial. Diabetes
Metab 2004; 30: 253–258
69. Wong ET, Rude RK, Singer FR et al. A high prevalence of
hypomagnesemia and hypermagnesemia in hospitalized pa-
tients. Am J Clin Pathol 1983; 79: 348–352
70. Chernow B, Bamberger S, Stoiko M et al. Hypomagnesemia in
patients in postoperative intensive care. Chest 1989; 95:
391–397
71. Whang R, Ryder KW. Frequency of hypomagnesemia and
hypermagnesemia. Requested vs routine. JAMA 1990; 263:
3063–3064
72. Ryzen E, Wagers PW, Singer FR et al. Magnesium deficiency in
a medical ICU population. Crit Care Med 1985; 13: 19–21
73. Bernstein L. Improving Magnesium Absorption and Bioavaili-
bility. Geriatric Times; 2002. 3
74. Ryan MP. Diuretics and potassium/magnesium depletion. Di-
rections for treatment. Am J Med 1987; 82: 38–47
75. Elliott C, Newman N, Madan A. Gentamicin effects on urinary
electrolyte excretion in healthy subjects. Clin Pharmacol Ther
2000; 67: 16–21
76. Wazny LD, Brophy DF. Amiloride for the prevention of am-
photericin B-induced hypokalemia and hypomagnesemia.
Ann Pharmacother 2000; 34: 94–97
77. June CH, Thompson CB, Kennedy MS et al. Correlation of
hypomagnesemia with the onset of cyclosporine-associated
hypertension in marrow transplant patients. Transplantation
1986; 41: 47–51
78. Lote CJ, Thewles A, Wood JA et al. The hypomagnesaemic
action of FK506: urinary excretion of magnesium and cal-
cium and the role of parathyroid hormone. Clin Sci (Lond)
2000; 99: 285–292
79. Lajer H, Daugaard G. Cisplatin and hypomagnesemia. Cancer
Treat Rev 1999; 25: 47–58
80. Tejpar S, Piessevaux H, Claes K et al. Magnesium wasting
associated with epidermal-growth-factor receptor-targeting
antibodies in colorectal cancer: a prospective study. Lancet
Oncol 2007; 8: 387–394
81. Broeren MA, Geerdink EA, Vader HL et al. Hypomagnesemia
induced by several proton-pump inhibitors. Ann Intern Med
2009; 151: 755–756
82. Otsuka M, Kanamori H, Sasaki S et al. Torsades de pointes
complicating pentamidine therapy of Pneumocystis carinii
pneumonia in acute myelogenous leukemia. Intern Med
1997; 36: 705–708
83. Huycke MM, Naguib MT, Stroemmel MM et al. A double-blind
placebo-controlled crossover trial of intravenous magnesium
sulfate for foscarnet-induced ionized hypocalcemia and hy-
pomagnesemia in patients with AIDS and cytomegalovirus
infection. Antimicrob Agents Chemother 2000; 44:
2143–2148
84. al-Ghamdi SM, Cameron EC, Sutton RA. Magnesium defi-
ciency: pathophysiologic and clinical overview. Am J Kidney
Dis 1994; 24: 737–752
85. Klein GL, Herndon DN. Magnesium deficit in major burns: role
in hypoparathyroidism and end-organ parathyroid hormone
resistance. Magnes Res 1998; 11: 103–109
86. Aglio LS, Stanford GG, Maddi R et al. Hypomagnesemia is
common following cardiac surgery. J Cardiothorac Vasc
Anesth 1991; 5: 201–208
87. Kuller L, Farrier N, Caggiula A et al. Relationship of diuretic
therapy and serum magnesium levels among participants in
the Multiple Risk Factor Intervention Trial. Am J Epidemiol
1985; 122: 1045–1059
88. Knoers NV. Inherited forms of renal hypomagnesemia: an
update. Pediatr Nephrol 2009; 24: 697–705
89. Xing JH, Soffer EE. Adverse effects of laxatives. Dis Colon
Rectum 2001; 44: 1201–1209
90. Fung MC, Weintraub M, Bowen DL. Hypermagnesemia. Eld-
erly over-the-counter drug users at risk. Arch Fam Med 1995;
4: 718–723
91. Clark BA, Brown RS. Unsuspected morbid hypermagnesemia
in elderly patients. Am J Nephrol 1992; 12: 336–343
Magnesium basics i13
at RWTH Aachen, on March 4, 2012http://ckj.oxfordjournals.org/Downloaded from
92. Kontani M, Hara A, Ohta S et al. Hypermagnesemia induced
by massive cathartic ingestion in an elderly woman without
pre-existing renal dysfunction. Intern Med 2005; 44: 448–452
93. Mordes JP, Wacker WE. Excess magnesium. Pharmacol Rev
1978; 29: 273–300
94. Onishi S, Yoshino S. Cathartic-induced fatal hypermagnese-
mia in the elderly. Intern Med 2006; 45: 207–210
95. Cao Z, Bideau R, Valdes R Jr et al. Acute hypermagnesemia
and respiratory arrest following infusion of MgSO
4
for tocol-
ysis. Clin Chim Acta 1999; 285: 191–193
96. Vissers RJ, Purssell R. Iatrogenic magnesium overdose: two
case reports. J Emerg Med 1996; 14: 187–191
97. Ali A, Walentik C, Mantych GJ et al. Iatrogenic acute hyper-
magnesemia after total parenteral nutrition infusion mim-
icking septic shock syndrome: two case reports. Pediatrics
2003; 112: e70–e72
98. Whang R, Whang DD. Update: mechanisms by which mag-
nesium modulates intracellular potassium. J Am Coll Nutr
1990; 9: 84–85
99. Escuela MP, Guerra M, Anon JM et al. Total and ionized serum
magnesium in critically ill patients. Intensive Care Med 2005;
31: 151–156
100. Huey CG, Chan KM, Wong ET et al. Los Angeles County-
University of Southern California Medical Center clinical
pathology case conference: extreme hypermagnesemia in
a neonate. Clin Chem 1995; 41: 615–618
101. Oren S, Rapoport J, Zlotnik M et al. Extreme hypermagnesemia
due to ingestion of Dead Sea water. Nephron 1987; 47: 199–201
102. Porath A, Mosseri M, Harman I et al. Dead Sea water poison-
ing. Ann Emerg Med 1989; 18: 187–191
103. Topf JM, Murray PT. Hypomagnesemia and hypermagnese-
mia. Rev Endocr Metab Disord 2003; 4: 195–206
104. Mathers TW, Beckstrand RL. Oral magnesium supplementa-
tion in adults with coronary heart disease or coronary heart
disease risk. J Am Acad Nurse Pract 2009; 21: 651–657
105. Fuentes JC, Salmon AA, Silver MA. Acute and chronic oral
magnesium supplementation: effects on endothelial function,
exercise capacity, and quality of life in patients with sympto-
matic heart failure. Congest Heart Fail 2006; 12: 9–13
106. Zipes DP, Camm AJ, Borggrefe M et al. ACC/AHA/ESC 2006
guidelines for management of patients with ventricular
arrhythmias and the prevention of sudden cardiac death:
a report of the American College of Cardiology/American
Heart Association Task Force and the European Society of
Cardiology Committee for Practice Guidelines (Writing Com-
mittee to Develop Guidelines for Management of Patients
With Ventricular Arrhythmias and the Prevention of Sudden
Cardiac Death): developed in collaboration with the European
Heart Rhythm Association and the Heart Rhythm Society.
Circulation 2006; 114: e385–e484
107. Krendel DA. Hypermagnesemia and neuromuscular trans-
mission. Semin Neurol 1990; 10: 42–45
108. Pritchard JA. The use of magnesium sulfate in preeclampsia-
eclampsia. J Reprod Med 1979; 23: 107–114
109. Turner JA. Diagnosis and management of pre-eclampsia: an
update. Int J Womens Health 2010; 2: 327–337
110. Golzarian J, Scott HW Jr, Richards WO. Hypermagnesemia-
induced paralytic ileus. Dig Dis Sci 1994; 39: 1138–1142
111. Berns AS, Kollmeyer KR. Magnesium-induced bradycardia.
Ann Intern Med 1976; 85: 760–761
112. Yoshida A, Itoh Y, Nagaya K et al. Prolonged relaxant effects
of vecuronium in patients with deliberate hypermagnese-
mia: time for caution in cesarean section. J Anesth 2006; 20:
33–35
113. ANZCA Guidelines. Management of pre-clampsia and eclam-
psia. 2011. http://www.anzca.edu.au/fellows/sig/obstetric-
anaesthesia-sig/obstetric-anaesthesia-scientific-evidence/
management-of-pre-eclampsia-and-eclampsia.html
114. McLaughlin SA, McKinney PE. Antacid-induced hypermagne-
semia in a patient with normal renal function and bowel
obstruction. Ann Pharmacother 1998; 32: 312–315
115. Jung GJ, Gil HW, Yang JO et al. Severe hypermagnesemia
causing quadriparesis in a CAPD patient. Perit Dial Int 2008;
28: 206
116. Kutsal E, Aydemir C, Eldes N et al. Severe hypermag-
nesemia as a result of excessive cathartic ingestion in a
child without renal failure. Pediatr Emerg Care 2007; 23:
570–572
117. Somjen G, Hilmy M, Stephen CR. Failure to anesthetize hu-
man subjects by intravenous administration of magnesium
sulfate. J Pharmacol Exp Ther 1966; 154: 652–659
118. Qureshi T, Melonakos TK. Acute hypermagnesemia after lax-
ative use. Ann Emerg Med 1996; 28: 552–555
119. Gerard SK, Hernandez C, Khayam-Bashi H. Extreme hy-
permagnesemia caused by an overdose of magnesium-
containing cathartics. Ann Emerg Med 1988; 17: 728–731
120. Smilkstein MJ, Smolinske SC, Kulig KW et al. Severe hyper-
magnesemia due to multiple-dose cathartic therapy. West
J Med 1988; 148: 208–211
121. Rizzo MA, Fisher M, Lock JP. Hypermagnesemic pseudocoma.
Arch Intern Med 1993; 153: 1130–1132
122. Tofil NM, Benner KW, Winkler MK. Fatal hypermagnesemia
caused by an Epsom salt enema: a case illustration. South
Med J 2005; 98: 253–256
i14 W. Jahnen-Dechent and M. Ketteler
at RWTH Aachen, on March 4, 2012http://ckj.oxfordjournals.org/Downloaded from
... Typical symptoms include problems such as cardiac arrythmia and an unusually slow heart ratebradycardia, which occur as a result of disrupted electrical signals in the heart. Other symptoms include nausea and vomiting, muscle weakness, shortness of breath and impaired tendon reflexes [63]. ...
Article
Full-text available
In total, twenty elements appear to be essential for the correct functioning of the human body, half of which are metals and half are non-metals. Among those metals that are currently considered to be essential for normal biological functioning are four main group elements, sodium (Na), potassium (K), magnesium (Mg), and calcium (Ca), and six d-block transition metal elements, manganese (Mn), iron (Fe), cobalt (Co), copper (Cu), zinc (Zn) and molybdenum (Mo). Cells have developed various metallo-regulatory mechanisms for maintaining a necessary homeostasis of metal-ions for diverse cellular processes, most importantly in the central nervous system. Since redox active transition metals (for example Fe and Cu) may participate in electron transfer reactions, their homeostasis must be carefully controlled. The catalytic behaviour of redox metals which have escaped control, e.g. via the Fenton reaction, results in the formation of reactive hydroxyl radicals, which may cause damage to DNA, proteins and membranes. Transition metals are integral parts of the active centres of numerous enzymes (e.Dg. Cu,Zn-SOD, Mn-SOD, Catalase) which catalyze chemical reactions at physiologically compatible rates. Either a deficiency, or an excess of essential metals may result in various disease states arising in an organism. Some typical ailments that are characterized by a disturbed homeostasis of redox active metals include neurological disorders (Alzheimer's, Parkinson's and Huntington's disorders), mental health problems, cardiovascular diseases, cancer, and diabetes. To comprehend more deeply the mechanisms by which essential metals, acting either alone or in combination, and/or through their interaction with non-essential metals (e.g. chromium) function in biological systems will require the application of a broader, more interdisciplinary approach than has mainly been used so far. It is clear that a stronger cooperation between bioinorganic chemists and biophysicists - who have already achieved great success in understanding the structure and role of metalloenzymes in living systems - with biologists, will access new avenues of research in the systems biology of metal ions. With this in mind, the present paper reviews selected chemical and biological aspects of metal ions and their possible interactions in living systems under normal and pathological conditions.
Article
Full-text available
Biodegradable magnesium (Mg) implants are emerging as a potential game changer in implant technology in situations where the implant temporarily supports the bone thereby avoiding secondary surgery for implant removal. However, the consequences of the alteration in the degradation rate to bone healing and the localization of degradation and alloying products in the long term remain unknown. In this study, we present the long-term osseointegration of three different biodegradable Mg alloys, Mg-10Gd, Mg-4Y-3RE and Mg-2Ag, which were implanted into rabbit femur for 6 and 9 months. In addition, we have investigated the effect of blood pre-incubation on the in vivo performance of the aforementioned alloys. Using high-resolution synchrotron radiation based micro computed tomography, the bone implant contact (BIC), bone volume fraction (BV/TV) and implant morphology were studied. The elemental traces have been characterized using micro X-ray fluorescence. Qualitative histological evaluation of the surrounding bone was also performed. Matured bone formed around all three implant types and Ca as well as P which represent parts of the degradation layer were in intimate contact with the bone. Blood pre-incubation prior to implantation significantly improved BIC in Mg-2Ag screws at 9 months. Despite different implant degradation morphologies pointing toward different degradation dynamics, Mg-10Gd, Mg-4Y-3RE and Mg-2Ag induced a similar long-term bone response based on our quantified parameters. Importantly, RE elements Gd and Y used in the alloys remained at the implantation site implying that they might be released later on or might persist in the implantation site forever. As the bone formation was not disturbed by their presence, it might be concluded that Gd and Y are non-deleterious. Consequently, we have shown that short and mid-term in vivo evaluations do not fully represent indicators for long-term osseointegration of Mg-based implants.
Article
Aim: To evaluate the relationship between long-term antenatal magnesium sulfate (MgSO4 ) administration and neonatal bone mineralization. Methods: Infants born at 28-33 weeks of gestation (n = 163) were divided into three groups: long-term Mg administration group (infants received antenatal MgSO4 for ≥40 days), short-term Mg administration group (infants received antenatal MgSO4 for <40 days), and non-Mg group. Serum calcium, phosphorus, Mg, and alkaline phosphatase were measured weekly up to 1 month of age, and the bone speed of sound (SOS) values were measured using quantitative ultrasound (QUS) at 1 week and 1 month after birth. Results: In the long-term Mg administration group, the serum calcium values were significantly lower, and the serum phosphorus, Mg, and alkaline phosphatase values were significantly higher than those in the non-Mg group at birth. Although these biochemical differences disappeared around the age of 2 weeks, the SOS values of the long-term Mg administration group were significantly lower than those of the non-Mg group both at 1 week and 1 month after birth (p = 0.02 and <0.001, respectively). When less than 10th percentile of SOS values at 1 month after birth in the non-Mg group was defined as poor bone mineralization, the cut-off value for the duration of antenatal MgSO4 administration was 67 days. Conclusions: Long-term antenatal MgSO4 administration affects bone mineralization during the early neonatal period, but the clinically acceptable duration of the administration based on its effects of bone mineralization assessed with QUS might be longer than a few weeks.
Article
Full-text available
Aims: Obstructive sleep apnoea (OSA) affects patients’ quality of life and health. Magnesium (Mg) is an essential mineral and a potent antioxidant. Mg deficiency can worsen oxidative stress caused by sleep deprivation or disorders. The impact of OSA on serum Mg levels and its health consequences remain unclear. Data Synthesis: This study systematically reviewed clinical studies investigating the serum Mg levels of OSA patients and the potential relationships with other biomarkers. Six articles were included for qualitative synthesis and quantitative analysis. Two out of four studies that compared OSA patients to healthy controls found them to have significantly lower serum Mg levels. Our meta-analysis with three studies shows that patients with OSA had significantly lower serum Mg with an effect size of −1.22 (95% CI: −2.24, −0.21). However, the mean serum Mg level of OSA patients (n = 251) pooled from five studies (1.90 mg/dL, 95% CI: 1.77, 2.04) does not differ significantly from the normal range between 1.82 to 2.30 mg/dL. OSA severity appears to affect serum Mg negatively. Serum Mg levels generally improve after treatment, coinciding with the improvement of OSA severity. Low serum Mg levels correlate with the worsening of cardiovascular risk biomarkers of C-reactive protein, ischaemia-modified albumin, and carotid intima-media thickness. The serum Mg levels also potentially correlate with biomarkers for lipid profile, glucose metabolism, calcium, and heavy metals. Conclusions: Sleep deprivation appears to deplete Mg levels of OSA patients, making them at risk of Mg deficiency, which potentially increases systemic inflammation and the risk of cardiovascular and metabolic diseases.
Article
Full-text available
Background Metals may influence reproductive health, but few studies have investigated correlates of metal body burden among reproductive-aged women outside of pregnancy. Furthermore, while there is evidence of racial disparities in exposure to metals among U.S. women, there is limited research about correlates of metal body burden among Black women. Objective To identify correlates of whole blood metal concentrations among reproductive-aged Black women. Methods We analyzed cross-sectional data from a cohort of 1664 Black women aged 23–35 years in Detroit, Michigan, 2010–2012. We collected blood samples and questionnaire data. We measured concentrations of 17 metals in whole blood using inductively-coupled plasma-mass spectrometer-triple quadrupole and total mercury using Direct Mercury Analyzer-80. We used multivariable linear regression models to identify sociodemographic, environmental, reproductive, and dietary correlates of individual metal concentrations. Results In adjusted models, age was positively associated with multiple metals, including arsenic, cadmium, and mercury. Education and income were inversely associated with cadmium and lead. Current smoking was strongly, positively associated with cadmium and lead. Alcohol intake in the past year was positively associated with arsenic, barium, copper, lead, mercury, vanadium, and zinc. Having pumped gasoline in the past 24 h was positively associated with cadmium, chromium, and molybdenum. Having lived in an urban area for the majority of residence in Michigan was positively associated with arsenic, lead, and nickel. Higher water intake in the past year was positively associated with several metals, including lead. Fish intake in the past year was positively associated with arsenic, cesium, and mercury. We also observed associations with body mass index, season, and other environmental, reproductive, and dietary factors. Significance We identified potential sources of exposure to metals among reproductive-aged Black women. Our findings improve understanding of exposures to metals among non-pregnant reproductive-aged women, and can inform policies in support of reducing disparities in exposures. Impact statement There are racial disparities in exposures to metals. We analyzed correlates of blood metal concentrations among reproductive-aged Black women in the Detroit, Michigan metropolitan area. We identified sociodemographic, anthropometric, lifestyle, environmental, reproductive, and dietary correlates of metal body burden. Age was positively associated with several metals. Education and income were inversely associated with cadmium and lead, indicating socioeconomic disparities. We identified potential exposure sources of metals among reproductive-aged Black women, including smoking, environmental tobacco smoke, pumping gasoline, living in an urban area, and intake of alcohol, water, fish, and rice.
Article
The coronavirus-disease 2019 (COVID-19) was announced as a global pandemic by the World Health Organization (WHO), and it affected all human groups. Severe COVID-19 is characterized by cytokine storms, which can lead to multiorgan failure and death, although fever and cough are the most typical symptoms of mild COVID-19. Plant-based diets provide a 73% lower risk of moderate-to-severe COVID-19. Additionally, the association between low levels of some micronutrients and the adverse clinical consequences of COVID-19 has been demonstrated. So, nutritional therapy can become part of patient care for the survival of this life-threatening disease (COVID-19) also short-term recovery. Magnesium as an essential micronutrient due to its anti-inflammatory and beneficial effects can effectively prevent COVID-19 pandemic by playing a role in the treatment of comorbidities such as diabetes and cardiovascular disorders as major risk factors for mortality. Sufficient magnesium to stay healthy is provided by a proper daily diet, and there is usually no need to take magnesium supplements. Considering that almost half of the dietary magnesium comes from fruits, vegetables, nuts, and grains, it seems necessary to pay attention to the consumption of edible plants containing sufficient magnesium as part of the diet to prevent severe COVID-19. In this study, we have described the beneficial effects of sufficient magnesium levels to control COVID-19 and the importance of plant-based magnesium-rich diets. Additionally, we have listed some edible magnesium-rich plants.
Article
Full-text available
Allosteric activation and silencing of leukocyte β2-integrins transpire through cation-dependent structural changes, which mediate integrin biosynthesis and recycling, and are essential to designing leukocyte-specific drugs. Stepwise addition of Mg²⁺ reveals two mutually coupled events for the αXβ2 ligand-binding domain—the αX I-domain—corresponding to allostery establishment and affinity maturation. Electrostatic alterations in the Mg²⁺-binding site establish long-range couplings, leading to both pH- and Mg²⁺-occupancy-dependent biphasic stability change in the αX I-domain fold. The ligand-binding sensorgrams show composite affinity events for the αX I-domain accounting for the multiplicity of the αX I-domain conformational states existing in the solution. On cell surfaces, increasing Mg²⁺ concentration enhanced adhesiveness of αXβ2. This work highlights how intrinsically flexible pH- and cation-sensitive architecture endows a unique dynamic continuum to the αI-domain structure on the intact integrin, thereby revealing the importance of allostery establishment and affinity maturation in both extracellular and intracellular integrin events.
Article
We determined concentrations of magnesium, total protein, albumin, and globulin in more than 74 000 serum specimens from patients and noted a direct linear relationship between the concentration of magnesium in serum and the concentrations of total protein, albumin, and globulin in serum. Albumin and magnesium concentrations are linearly related at high and low albumin concentrations; within the reference interval, however, the magnesium concentration is independent of the albumin concentration. Linear regression analysis suggests that 25% of the total serum magnesium is bound to albumin and 8% to globulins.
Article
The prevalence of hypomagnesemia and hypermagnesemia among hospitalized patients was studied by determining magnesium levels in 621 serum samples randomly selected from those submitted to the clinical chemistry laboratory for a biochemical test panel. The reference range for serum magnesium was established in this study as 1.2 to 1.9 mEq/L from measurements of serum magnesium on 341 healthy volunteers. Hypomagnesemia (<1.2 mEq/L) was present in 68 patients or 11.0%, and hypermagnesemia (>1.9 mEq/L) occurred in 58 patients or 9.3%. The degree of association between hypomagnesemia and hypocalcemia was assessed by measuring serum magnesium on a separate group of 61 patients with hypocalcemia (corrected calcium <8.6 mg/dL). Hypomagnesemia was present in 23.3 % of patients hypocalcemic in the absence of renal failure; this proportion was higher significantly than the 11.0% who were hypomagnesemic in the hospitalized patient group (P < 0.025).
Article
Magnesium has an established role in obstetrics and an evolving role in other clinical areas, in particular cardiology. Many of the effects involving magnesium are still a matter of controversy. Over the next decade, it is likely that improvements in the measurement of magnesium, a clearer understanding of the mechanisms of its actions and further results of clinical studies will help to elucidate its role, both in terms of treating deficiency and as a pharmacological agent.
Conference Paper
Children and adults who are severely burned develop magnesium(Mg) depletion, hypocalcemia, hypoparathyroidism and renal resistance to the administration of exogenous parathyroid hormone(PTH). This same spectrum of findings is seen with both Mg depletion and hypermagnesemia. We reported that in a group of ten children burned at least 30 per cent of total body surface area that 70-80 per cent of serum levels of ionized calcium and Mg were low. In three of the patients studied when serum Mg returned to normal, retention of a standard Mg infusion was abnormally high in two of them, suggesting persistence of Mg depletion despite normal serum Mg levels. Mg intake in these children conforms to the recommended dietary intake for age suggesting that excessive Mg losses may contribute to the observed Mg depletion. These losses are through the burn wound and possibly through abnormal intestinal secretion. Increased metabolic rate seen in burn patients may also promote intracellular Mg uptake to support the increased energy requirements of cells. It is hypothesized that since Mg is an important cofactor in the production of cyclic AMP, Mg deficiency may block intracellular cyclic AMP generation in parathyroid cells to block the secretion of parathyroid hormone and in renal tubular cells to block the renal generation of cyclic AMP and phosphate excretion. However, while Mg administration may improve PTH secretion and hypocalcemia in non-burned patients, preliminary data in burned children suggest that the cause of hypocalcemia and hypoparathyroidism is more complex.
Article
In physiological studies of the major inorganic constituents of heart muscle cells, magnesium (Mg) has until recently been neglected. There are several reasons for this neglect. Chemical analysis for Mg was for many years difficult and tedious. The only available radioactive isotope of Mg, 28Mg, is expensive and has a short half life. Moreover, Mg acts on relatively inaccessible intracellular processes some of which have been identified and measured only in tissue fractions or in purified proteins extracted from cells; the intracellular processes in which Mg is implicated are multiple and themselves poorly understood. The ionized Mg concentration ([Mg2+]) in the cardiac cell cannot at present be directly determined, and the rate at which Mg is transported into and out of myocardial cells is so much slower than the rates for potassium, sodium, calcium, and chloride that isotopic or electrophysiological measurements of ion transport in the usual in vitro preparations of heart muscle become insensitive or inconvenient. Nevertheless, there are compelling reasons for reexamining the role of Mg in heart muscle at this time. First, recent experiments on skeletal muscle indicate that [Mg2+] may be a critical modulator of the tension with which the contractile apparatus of striated muscle responds to the prevailing ionized calcium concentration ([Ca2+]); at the same time, the Mg complex with adenosine triphosphate (MgATP) is the substrate for the enzymatic reactions that underlie the sliding filament mechanism for myofibrillar contraction and relaxation. Second, work with subcellular model systems indicates that Mg participates in many of the most vital oxidative, synthetic, and transport processes of the myocardial cell. Finally, advances in the microchemical and radioactive measurement of Mg as well as in the diversity and suitability of available heart muscle preparations have greatly simplified the problems of working with this element.