1RWTH Aachen College, Helmholtz Institute for Biomedical Engineering, Biointerface Laboratory, Aachen, Germany
2Klinikum Coburg, III. Medizinische Klinik, Coburg, Germany
Summary
Introduction
Magnesium is the eighth commonest ingredient within the crust of the Earth [1, 2] and is especially tied up inside mineral deposits, for instance as magnesite (magnesium carbonate [MgCO3]) and dolomite. Dolomite CaMg(CO3)2 is, because the title suggests, plentiful within the Dolomite mountain vary of the Alps [3]. Probably the most plentiful supply of biologically accessible magnesium, nonetheless, is the hydrosphere (i.e. oceans and rivers). Within the sea, the focus of magnesium is ∼55 mmol/L and within the Useless Sea—as an excessive instance—the focus is reported to be 198 mmol/L magnesium [4] and has steadily elevated over time.
Magnesium salts dissolve simply in water and are way more soluble than the respective calcium salts. Consequently, magnesium is available to organisms [5]. Magnesium performs an vital position in vegetation and animals alike [2]. In vegetation, magnesium is the central ion of chlorophyll [3]. In vertebrates, magnesium is the fourth most plentiful cation [5, 6] and is important, particularly inside cells, being the second commonest intracellular cation after potassium, with each these components being very important for quite a few physiological features [6–9]. Magnesium can also be used broadly for technical and medical functions starting from alloy manufacturing, pyrotechnics and fertilizers to well being care. Historically, magnesium salts are used as antacids or laxatives within the type of magnesium hydroxide [Mg(OH)2], magnesium chloride (MgCl2), magnesium citrate (C6H6O7Mg) or magnesium sulphate (MgSO4).
Chemical traits
Magnesium is a Group 2 (alkaline earth) ingredient throughout the periodic desk and has a relative atomic mass of 24.305 Da [7], a particular gravity at 20°C of 1.738 [2, 3], a melting level of 648.8°C [2] and a boiling level of 1090°C [3]. Within the dissolved state, magnesium binds hydration water tighter than calcium, potassium and sodium. Thus, the hydrated magnesium cation is difficult to dehydrate. Its radius is ∼400 instances bigger than its dehydrated radius. This distinction between the hydrated and the dehydrated state is way more outstanding than in sodium (∼25-fold), calcium (∼25-fold) or potassium (4-fold) [5]. Consequently, the ionic radius of dehydrated magnesium is small however biologically related [6]. This straightforward truth explains quite a lot of magnesium’s peculiarities, together with its usually antagonistic behaviour to calcium, regardless of comparable chemical reactivity and cost. As an example, it’s nearly not possible for magnesium to move by means of slender channels in organic membranes that may be readily traversed by calcium as a result of magnesium, in contrast to calcium, can’t be simply stripped of its hydration shell [10]. Steric constraints for magnesium transporters are additionally far better than for some other cation transport system [5]: proteins transporting magnesium are required to acknowledge the big hydrated cation, strip off its hydration shell and ship the naked (i.e. dehydrated) ion to the transmembrane transport pathway by means of the membrane (Determine 1) [5, 11, 12]. There are apparent chemical similarities between calcium and magnesium however in cell biology, main variations usually prevail (Desk 1).
Physiological position of magnesium within the physique
The physique of most animals accommodates ∼0.4 g magnesium/kg [5]. The overall magnesium content material of the human physique is reported to be ∼20 mmol/kg of fat-free tissue. In different phrases, complete magnesium within the common 70 kg grownup with 20% (w/w) fats is ∼1000 [7] to 1120 mmol [13] or ∼24 g [14, 15]. These values must be interpreted with warning, nonetheless, as analytical strategies differ significantly all through the years. As compared, the physique content material of calcium is ∼1000 g (i.e. 42 instances better than the physique content material of magnesium) [16].
Distribution within the human physique – “m magnesium complex”
About 99% of complete physique magnesium is situated in bone, muscle tissues and non-muscular mushy tissue [17] (see additionally Desk 2). Roughly 50–60% of magnesium resides as floor substituents of the hydroxyapatite mineral element of bone [14, 18]. An illustration of bioapatite is proven in Determine 2. Many of the remaining magnesium is contained in skeletal muscle and mushy tissue [14]. The magnesium content material of bone decreases with age, and magnesium saved on this means just isn’t utterly bioavailable throughout magnesium deprivation [5]. Nonetheless, bone supplies a big exchangeable pool to buffer acute adjustments in serum magnesium focus [19]. Total, one third of skeletal magnesium is exchangeable, serving as a reservoir for sustaining physiological extracellular magnesium ranges [19].
Intracellular magnesium concentrations vary from 5 to twenty mmol/L; 1–5% is ionized, the rest is sure to proteins, negatively charged molecules and adenosine triphosphate (ATP) [18].
Extracellular magnesium accounts for ∼1% of complete physique magnesium [14, 18, 20] which is primarily present in serum and pink blood cells (RBCs) [5, 7, 21, 22]. Serum magnesium can—similar to calcium—be categorized into three fractions. It’s both free/ionized, sure to protein or complexed with anions resembling phosphate, bicarbonate and citrate or sulphate (Desk 1, Determine 3). Of the three fractions in plasma, nonetheless, ionized magnesium has the best organic exercise [5, 7, 21, 22].
Magnesium is primarily discovered throughout the cell [7] the place it acts as a counter ion for the energy-rich ATP and nuclear acids. Magnesium is a cofactor in >300 enzymatic reactions [8, 10]. Magnesium critically stabilizes enzymes, together with many ATP-generating reactions [14]. ATP is required universally for glucose utilization, synthesis of fats, proteins, nucleic acids and coenzymes, muscle contraction, methyl group switch and plenty of different processes, and interference with magnesium metabolism additionally influences these features [14]. Thus, one ought to take into account that ATP metabolism, muscle contraction and rest, regular neurological perform and launch of neurotransmitters are all magnesium dependent. Additionally it is vital to notice that magnesium contributes to the regulation of vascular tone, coronary heart rhythm, platelet-activated thrombosis and bone formation (see evaluate by Cunningham et al. [28] on this complement) [6, 7, 10, 29, 30]. A few of magnesium’s many features are listed in Desk 3.
In muscle contraction, for instance, magnesium stimulates calcium re-uptake by the calcium-activated ATPase of the sarcoplasmic reticulum [14]. Magnesium additional modulates insulin sign transduction and cell proliferation and is vital for cell adhesion and transmembrane transport together with transport of potassium and calcium ions. It additionally maintains the conformation of nucleic acids and is important for the structural perform of proteins and mitochondria.
It has lengthy been suspected that magnesium might have a task in insulin secretion owing to the altered insulin secretion and sensitivity noticed in magnesium-deficient animals [31]. Epidemiological research have proven a excessive prevalence of hypomagnesaemia and decrease intracellular magnesium concentrations in diabetics. Advantages of magnesium supplementation on the metabolic profile of diabetics have been noticed in some, however not all, medical trials, and so bigger potential research are wanted to find out if dietary magnesium supplementation is related to helpful results on this group [32].
Latest epidemiological research have instructed {that a} comparatively younger gestational age is related to magnesium deficiency throughout being pregnant, which not solely induces maternal and foetal dietary issues but additionally results in different penalties which may have an effect on the offspring all through life [33].
There’s additionally proof that magnesium and calcium compete with each other for a similar binding websites on plasma protein molecules [13, 34]. It was proven that magnesium antagonizes calcium-dependent launch of acetylcholine at motor endplates [6]. Thus, magnesium could also be thought-about a pure ‘calcium antagonist’. Whereas calcium is a strong ‘death trigger’ [35], magnesium just isn’t [34]: magnesium inhibits calcium-induced cell dying [36]. It’s anti-apoptotic in mitochondrial permeability transition and antagonizes calcium-overload-triggered apoptosis. Magnesium is vital in well being and illness, as will probably be mentioned in additional element on this complement within the article by Geiger and Wanner [37].
Regulation of magnesium inflow and efflux
There’s appreciable variation within the plasma/tissue trade of magnesium between numerous organs of an animal and likewise between animal species [5]. These observations point out that numerous cell varieties deal with magnesium fairly otherwise, which is once more totally different from calcium [10]. Myocardium, kidney parenchyma, fats tissue, skeletal muscle, mind tissue and lymphocytes trade intracellular and extracellular magnesium at totally different charges. In mammalian coronary heart, kidney and adipocytes, complete intracellular magnesium is ready to trade with plasma magnesium inside 3–4 h [38–42]. In man, equilibrium for magnesium amongst most tissue compartments is reached very slowly, if in any respect [17]. About 85% of the entire physique magnesium, measured as [28]Mg is both non-exchangeable or exchanges very slowly with a roughly estimated organic half-life of ∼1000 h [43].
Magnesium consumption
People have to devour magnesium often to forestall magnesium deficiency, however because the really useful each day allowance for magnesium varies, it’s tough to outline precisely what the precise optimum consumption must be. Values of ≥300 mg are normally reported with adjusted dosages for age, intercourse and dietary standing. The Institute of Drugs recommends 310–360 mg and 400–420 mg for grownup ladies and men, respectively. Different suggestions within the literature recommend a decrease each day minimal consumption of 350 mg for males and 280–300 mg magnesium for girls (355 mg throughout being pregnant and lactation) [2, 7, 10, 18].
Whereas consuming water accounts for ∼10% of each day magnesium consumption [44], chlorophyll (and thus inexperienced greens) is the foremost supply of magnesium. Nuts, seeds and unprocessed cereals are additionally wealthy in magnesium [15]. Legumes, fruit, meat and fish have an intermediate magnesium focus. Low magnesium concentrations are present in dairy merchandise [7]. It’s noteworthy that processed meals have a a lot decrease magnesium content material than unrefined grain merchandise [7] and that dietary consumption of magnesium within the western world is lowering owing to the consumption of processed meals [45]. With the omnipresence of processed meals, boiling and consumption of de-mineralized mushy water, most industrialized nations are disadvantaged of their pure magnesium provide. However, magnesium dietary supplements are very fashionable meals dietary supplements, particularly within the bodily lively.