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Magnesium Basics


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.
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Clin Kidney J (2012) 5[Suppl 1]: i3–i14
doi: 10.1093/ndtplus/sfr163
Magnesium basics
Wilhelm Jahnen-Dechent
and Markus Ketteler
RWTH Aachen University, Helmholtz Institute for Biomedical Engineering, Biointerface Laboratory, Aachen, Germany and
Coburg, III. Medizinische Klinik, Coburg, Germany
Correspondence and offprint requests to: Wilhelm Jahnen-Dechent; E-mail:
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
Keywords: magnesium; physicochemical properties; physiological function; regulation; hypomagnesaemia;
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
]) and dolomite. Dolomite CaMg(CO
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
], magnesium chloride (MgCl
), magnesium cit-
rate (C
Mg) or magnesium sulphate (MgSO
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
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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:
Mg (most abundant isotope)
Ca (most abundant isotope)
Mg radioactive, b-decay
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
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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
Body weight
(kg wet
(mmol/kg wet
% of total
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
, phosphate; CO
, 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
. Reprinted from [8], with
Enzyme function
Enzyme substrate (ATP-Mg, GTP-Mg)
Kinases B
Creatine kinase
Protein kinase
ATPases or GTPases
Adenylate cyclase
Guanylate cyclase
Direct enzyme activation
Creatine kinase
5-Phosphoribosyl-pyrophosphate synthetase
Adenylate cyclase
Membrane function
Cell adhesion
Transmembrane electrolyte flux
Calcium antagonist
Muscle contraction/relaxation
Neurotransmitter release
Action potential conduction in nodal tissue
Structural function
Nucleic acids
Multiple enzyme complexes
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
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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
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
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, 2012 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:
Red blood cells
Metabolic assessment via:
Balance studies
Isotopic analyses
Renal excretion of magnesium
Retention of magnesium, following acute administration
Free magnesium levels with:
Fluorescent probes
Ion-selective electrodes
Nuclear magnetic resonance spectroscopy
Metallochrome dyes
Red blood cell magnesium concentration does not seem to correlate well
with total body magnesium status [53].
Magnesium content of mononuclear cells may be a better predictor of
skeletal and cardiac muscle magnesium content [54].
Muscle is an appropriate tissue for the assessment of magnesium status
[55] but it is an invasive and expensive procedure requiring special expertise.
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.
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].
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.
Nuclear magnetic resonance may be used to measure intracellular free
magnesium concentration [10].
Magnesium basics i7
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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
¨rztliche Abrechnung; valuation standard) ¼1.40 V;
¨3621 1.00 (GOA
¨hrenordnung fu
¨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
Isotopic analysis of magnesium
Magnesium exists in three different isotopes: 78.7% occurs
Mg, 10.1% as
Mg and 11.2% as
Mg [5].
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.
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—
Mg—is only 21 h, restricting its
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.
, Ni
and Co
) 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
that can replace magne-
sium in the majority of enzymes where ATP-Mg is used as a
substrate [5].
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
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
i8 W. Jahnen-Dechent and M. Ketteler
at RWTH Aachen, on March 4, 2012 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:
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
[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
[7, 8]
Syndrome of inappropriate anti-diuretic hormone hypersecretion
Diabetes mellitus [6, 8]
Other causes:
Chronic alcoholism
[7, 8]
Excessive lactation, heat, prolonged exercise [6]
Severe burns [6, 85]
Cardiopulmonary bypass surgery [86]
Iatrogenic [6]
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].
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].
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
Positive Trousseau’s
ECG, electrocardiogram.
Sign of tetany, an abnormal reaction (i.e. facial twitching) seen as a reac-
tion to the tapping of the facial nerve.
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, 2012 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].
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].
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-
#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, 2012 from
Table 7. Clinical manifestations of hypermagnaesemia
Serum Mg (mmol/L)
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
, 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
[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)
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
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]
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.
Symptom also used for monitoring purposes in eclampsia [109]
AV, atrio-ventricular; Mg, magnesium; MgSO
, magnesium sulphate; PD, peritoneal dialysis.
Magnesium basics i11
at RWTH Aachen, on March 4, 2012 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
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.
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... As the magnesium metal degrades, it is transformed into magnesium salts and hydrogen gas, both of which are resorbed by the body [22,23]. The degradation process causes an influx of magnesium ions, which are naturally present within almost every cell of the body and are involved in many important processes [24,25]. The daily recommended intake of magnesium is between 300 and 350 mg for adults [26], which is higher than the weight of the largest pure magnesium membrane, which is approximately 280 mg [17]. ...
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Due to their specific morphology, the regeneration of intrabony defects (IBDs) represents one of the greatest challenges for clinicians. Based on the specific properties of a magnesium membrane, a new approach for the surgical treatment of IBD was developed. The surgical procedure was described using a series of three cases. Materials and Methods: The patients were healthy individuals suffering from a severe form of periodontitis associated with IBD. Based on radiographic examination, the patients had interproximal bone loss of at least 4 mm. Due to its good mechanical properties, it was easy to cut and shape the magnesium membrane into three different shapes to treat the specific morphology of each IBD. In accordance with the principles of guided bone regeneration, a bovine xenograft was used to fill the IBD in all cases. Results: After a healing period of 4 to 6 months, successful bone regeneration was confirmed using radiological analysis. The periodontal probing depth (PPD) after healing showed a reduction of 1.66 ± 0.29 mm. Conclusions: Overall, the use of the different shapes of the magnesium membrane in the treatment of IBD resulted in a satisfactory functional and esthetic outcome.
... Potassium/sodium balance is fundamental for the transmission of electrical impulses in the heart [51]. Magnesium is an important mineral in protein synthesis, oxidative phosphorylation, the regulation of body temperature and muscle contractions, and it is a cofactor for many enzymes [52]. Calcium is also another important element required for blood clotting, growth, bone formation, cell metabolism, and heart function [53,54]. ...
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Physalis species are used as an indigenous food and medicine in Kenya. However, species identification and an analysis of the health-promoting bioactive compounds and antioxidant properties are lacking. In this study, we report the molecular identification and mineral and phytochemical profiling of wild Physalis accessions. Leaf samples of 10 Physalis accessions were collected and used for species identification using nuclear ITS2 and plastid rbcL barcodes. Ripe fruits were collected from the same accessions and analyzed for mineral, total phenolic, tannin, and flavonoid contents, and antioxidant activities. The Physalis species were discriminated based on the ITS2 barcode and identified as Physalis purpurea. The genetic diversity, distance, and polymorphism of the ITS2 region of Physalis accessions were high due to the high rate of singleton and parsimony mutations. No genetic diversity, distance, or polymorphism was observed based on the rbcL barcode. The mineral content was significantly different (p < 0.05) for calcium, zinc, nickel, copper, and lithium among the Physalis accessions. No significant variation (p > 0.05) was found for phenolic acids or flavonoids, but the tannic acid content varied significantly (p < 0.05). DPPH free radical scavenging varied significantly (p < 0.05) among Physalis accessions. In conclusion, nuclear ITS2 was used to successfully identify the Physalis species of all the accessions as Physalis purpurea. The present study confirmed that Physalis purpurea has a significantly high mineral and phytochemical content and antioxidant activity. The findings from this study can be used to facilitate exploitation of Physalis purpurea in genetic breeding, their application in pharmaceutical, cosmetic, and nutritional value as well as conservation and sustainable use.
... It is widely recognized that reduced intestinal absorption or increased urine excretion might result in Mg deficiency. 71 Since Mg naturally exists in a variety of foods, reduced dietary intake cannot be a cause of Mg insufficiency. 72 Either alcoholics, patients with renal issues, individuals taking certain drugs, or people who have the celiac condition may have trouble in absorbing Mg. 73 We have found that there was no difference between PE and normal pregnancy in terms of urinary Mg levels or fractional excretion of Mg, demonstrating the lack of aberrant excretion. ...
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Preeclampsia (PE) is characterized by new onset hypertension and proteinuria. Undoubtedly, some individuals do not fit precisely into this description, and it could be challenging to spot newly developed PE in females who already have hypertension or renal illness. Monitoring the disease’s progression enables the optimization of delivery time while minimizing premature births. The current study explores the diagnostic benefits of serum endostatin and cystatin C in addition to serum and urinary magnesium (Mg) and fractional excretion magnesium (FEMg) for early prediction of PE. The population sample included 82 pregnant women divided into 3 groups: normal pregnancy group served as a control (n = 26), nonpreeclampsia (NPE, n = 34) group included pregnant women with one or more risk factors but did not progress to PE, and pregnant women who developed preeclampsia (PE, n = 22) group. Blood samples were withdrawn at two sampling times: at 12th to 16th and 24th to 26th weeks of gestation. Compared to normal pregnancy, results (X̅ ± SD) indicated a significant increase in serum endostatin in NPE at the first sample (10.78 ± 3.63 ng/mL) and the second sample (28.03 ± 3.79 ng/mL), while cystatin C was at the first sample (0.68 ± 0.06 mg/dL) and the second sample (0.71 ± 0.07 mg/dL). In the PE group, the serum endostatin was 18.86 ± 4.37 ng/mL at the first sampling time and 53.56 ± 9.76 ng/mL for the second sample. Serum cystatin C was also elevated in PE with X̅ ± SD equivalent to 0.73 ± 0.08 and 0.89 ± 0.08 mg/dL at the first and second samples, respectively. On the other hand, serum and urinary Mg in addition to FEMg levels did not significantly differ across the groups under study. Receiver operating characteristic (ROC) curve analysis proved that both endostatin and cystatin C could be good indicators for PE. The findings imply that measuring endostatin and cystatin C at early pregnancy and before progression to PE may be effective in detecting the likelihood of PE. Endostatin could be more precise and sensitive in assessing the probability of PE than cystatin C; however, coupling of the two parameters may be promising.
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Magnesium ions (Mg²⁺) play an essential role in cellular physiology. In mitochondria, protein and ATP synthesis and various metabolic pathways are directly regulated by Mg²⁺. MRS2, a magnesium channel located in the inner mitochondrial membrane, mediates the influx of Mg²⁺ into the mitochondrial matrix and regulates Mg²⁺ homeostasis. Knockdown of MRS2 in human cells leads to reduced uptake of Mg²⁺ into mitochondria and disruption of the mitochondrial metabolism. Despite the importance of MRS2, the Mg²⁺ translocation and regulation mechanisms of MRS2 are still unclear. Here, using cryo-EM we report the structures of human MRS2 in the presence and absence of Mg²⁺ at 2.8 Å and 3.3 Å, respectively. From the homo-pentameric structures, we identify R332 and M336 as major gating residues, which are then tested using mutagenesis and two cellular divalent ion uptake assays. A network of hydrogen bonds is found connecting the gating residue R332 to the soluble domain, potentially regulating the gate. Two Mg²⁺-binding sites are identified in the MRS2 soluble domain, distinct from the two sites previously reported in CorA, a homolog of MRS2 in prokaryotes. Altogether, this study provides the molecular basis for understanding the Mg²⁺ translocation and regulatory mechanisms of MRS2.
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Aims/hypothesis Hypomagnesaemia has been associated with insulin resistance and an increased risk of type 2 diabetes. Whether magnesium supplementation improves insulin sensitivity in people with type 2 diabetes and a low serum magnesium level is unknown. Methods Using a randomised, double-blind (both participants and investigators were blinded to the participants’ treatment sequences), placebo-controlled, crossover study design, we compared the effect of oral magnesium supplementation (15 mmol/day) for 6 weeks with that of matched placebo in individuals with insulin-treated type 2 diabetes (age ≥18 years, BMI 18–40 kg/m², HbA1c <100 mmol/mol [11.3%], serum magnesium ≤0.79 mmol/l). Participants were recruited from the outpatient clinic and through advertisements. Randomisation to a treatment sequence order was done using a randomisation list. We used block randomisation and the two possible treatment sequences were evenly distributed among the trial population. The primary outcome was the mean glucose infusion rate during the final 30 min of a hyperinsulinaemic–euglycaemic clamp (i.e. M value). Secondary outcomes included variables of glucose control, insulin need, BP, lipid profile and hypomagnesaemia-related symptoms during follow-up. Results We recruited 14 participants (50% women, 100% White, mean ± SD age 67±6 years, BMI 31±5 kg/m², HbA1c 58±9 mmol/mol [7.4±0.9%]) with insulin-treated type 2 diabetes. Magnesium supplementation increased both mean ± SEM serum magnesium level (0.75±0.02 vs 0.70±0.02 mmol/l, p=0.016) and urinary magnesium excretion (magnesium/creatinine ratio, 0.23±0.02 vs 0.15±0.02, p=0.005), as compared with placebo. The M value of the glucose clamp did not differ between the magnesium and placebo study arms (4.6±0.5 vs 4.4±0.6 mg kg⁻¹ min⁻¹, p=0.108). During the 6 weeks of treatment, continuous glucose monitoring outcomes, HbA1c, insulin dose, lipid profile and BP also did not differ, except for a lower HDL-cholesterol concentration after magnesium compared with placebo (1.14±0.08 vs 1.20±0.09 mmol/l, p=0.026). Symptoms potentially related to hypomagnesaemia were similar for both treatment arms. Conclusions/interpretation Despite an albeit modest increase in serum magnesium concentration, oral magnesium supplementation does not improve insulin sensitivity in people with insulin-treated type 2 diabetes and low magnesium levels. Trial registration EudraCT number 2021-001243-27. Funding This study was supported by a grant from the Dutch Diabetes Research Foundation (2017–81–014). Graphical Abstract
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Sufficient mineral supply is vital not only for the innate immune system but also for the components of the adaptive immune defense, which encompass defense mechanisms against pathogens and the delicate balance of pro-and anti-inflammatory regulation in the long term. Generally, a well-balanced diet is capable of providing the necessary minerals to support the immune system. Nevertheless, specific vulnerable populations should be cautious about obtaining adequate amounts of minerals such as magnesium , zinc, copper, iron, and selenium. Inadequate levels of these minerals can temporarily impair immune competence and disrupt the long-term regulation of systemic inflammation. Therefore, comprehending the mechanisms and sources of these minerals is crucial. In exceptional circumstances, mineral deficiencies may necessitate supplementation; however, excessive intake of supplements can have adverse effects on the immune system and should be avoided. Consequently, any supplementation should be approved by medical professionals and administered in recommended doses. This review emphasizes the crucial significance of minerals in promoting optimal functioning of the immune system. It investigates the indispensable minerals required for immune system function and the regulation of inflammation. Moreover, it delves into the significance of maintaining an optimized intake of minerals from a nutritional standpoint.
Background: There is a lack of consensus on a reference range for ionized magnesium (iMg2+) in blood as a measure of status of circulating iMg2+ for screening populations. Objectives: We estimated the reference range of iMg2+ levels for healthy adult populations and the ranges for populations with cardiovascular disease (CVD), type 2 diabetes, hypertension, and renal disease. We also estimated 95% ranges for circulating magnesium (Mg) in healthy and those with cardiometabolic diseases. Methods: We searched Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Embase through 24 July 2020 to identify articles. We included English, peer-reviewed, randomized controlled trials, prospective and retrospective cohort studies, case-control studies, and cross-sectional studies that measured iMg2+ in blood or circulating Mg at baseline. The protocol was registered on PROSPERO (CRD42020216100). Estimated ranges were calculated by employing a frequentist random-effects model using extracted (or calculated) means and standard deviations from each included study. We determined the 95% confidence interval of the pooled mean. Results: A total of 95 articles were included with 53 studies having data for healthy participants and 42 studies having data for participants with cardiometabolic diseases. The estimated reference range for iMg2+ for healthy populations was 0.40-0.68 mmol/L, 0.38 - 0.64 mmol/L for CVD, 0.34 - 0.66 mmol/L for type 2 diabetes, 0.39 -1.04 mmol/L for hypertension, and 0.40 - 0.76 mmol/L for renal disease. For circulating Mg, the estimated range was 0.72-1.0 mmol/L for healthy adults, 0.56 - 1.05 mmol/L for CVD, 0.58 - 1.14 mmol/L for type 2 diabetes, 0.60 -1.08 mmol/L for hypertension, and 0.59 - 1.26 mmol/L for renal disease. Conclusions: Estimated reference ranges for cardiometabolic disease states for both iMg2+ and circulating Mg were broad and overlapped with the estimated range for healthy populations (0.40-0.68 mmol/L). Further studies should evaluate whether iMg2+ can be used as a biomarker of cardiometabolic disease.
Metal ions are indispensable elements in living organisms and are associated with regulating various biological processes. An imbalance in metal ion content can lead to disorders in normal physiological functions of the human body and cause various diseases. Genetically encoded fluorescent protein sensors have the advantages of low biotoxicity, high specificity, and a long imaging time in vivo and have become a powerful tool to visualize or quantify the concentration level of biomolecules in vivo and in vitro, temporal and spatial distribution, and life activity process. This review analyzes the development status and current research hotspots in the field of genetically encoded fluorescent protein sensors by bibliometric analysis. Based on the results of bibliometric analysis, the research progress of genetically encoded fluorescent protein sensors for metal ion detection is reviewed, and the construction strategies, physicochemical properties, and applications of such sensors in biological imaging are summarized.
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Insomnia is increasing day by day, according to global prevalence it ranges from10%to40%with trouble falling asleep, remaining asleep, or having non-restorative sleep that is accompanied by daytime impairment or distress. Magnesium seems to play a key role in there gelation of sleep. Objective: To compare the therapeutic effect of magnesium supplementation in improving quality of life among elderly insomniac participants with control and treatment group. Methods: The study design was double blind randomized clinical trial. Purposive sampling technique was used to allocate gender elderly people. Data were collected from Al-Saida Shuhda old age home, Lahore and the participants were divided into two groups, 40 participants in each group. Group 0 (control group) were given regular diet without magnesium supplement for 8 weeks. Group 1 (treatment group were given Magnesium supplements (500mg) for 8 weeks. Data were tabulated and analyzed with the help of SPSS 25.0. Results: The results shown that the magnesium supplementation had highly significant results in improving LSEQ, serum magnesium, serum melatonin, serum cortisol and serum renin level without showing any side effects. Group 0 has shown 0.152 (GTS), 0.088(QOS), 0.168(AFS), 0.195(BFW), 0.292(serum Mg), 0.567(serum melatonin), 0.276(serum cortisol), 0.101(serum renin) whereas group 1 has shown 0.01(GTS), 0.01(QOS), 0.003(AFS) and 0.03(BFW), 0.02(serum Mg), 0.01(serum melatonin), 0.02(serum cortisol), 0.02(serum renin), respectively. Conclusions: It was concluded from the results that magnesium supplementation in elderly people has highly significant effects in improving insomnia and quality of sleep.
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Background: Magnesium (Mg) disorders are common among hospitalized patients and are linked to poor health outcomes. We aimed to determine the incidence of dysmagnesemia among medically hospitalized patients and to identify factors that are associated with dysmagnesemia. Methods: A prospective cohort study was conducted at Sultan Qaboos University Hospital (SQUH) from April 1st, 2022, to October 31st, 2022, and involved hospitalized adult patients (≥18 years) under the care of the general internal medicine unit. The patients' serum total magnesium (Mg) concentrations were categorized as hypomagnesemia (≤0.69 mmol/L), hypermagnesemia (≥1.01 mmol/L), or dysmagnesemia, which encompassed either hypomagnesemia or hypermagnesemia. Results: Of the 304 patients evaluated, dysmagnesemia was observed in 22.0%, which comprised of 17.4% with hypomagnesemia and 4.6% with hypermagnesemia. Statistically significant associations were identified between hypermagnesemia and chronic kidney disease (CKD) (p = 0.05) and elevated creatinine levels (p < 0.01) and lower estimated glomerular filtration rate (eGFR) (p < 0.01). Hypomagnesemia was linked to lower ionized calcium (p = 0.03) and admission due to infectious diseases (p = 0.02). However, ordered regression analysis did not find any significant associations with the different magnesium groups. Conclusion: Dysmagnesemia was prevalent among hospitalized patients and was associated with different factors; however, ordered regression analysis did not find any association with the different magnesium group, probably due to the limited number of included individuals.
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.
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).
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.
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.