Magnesium is an element of the alkaline earth group and bears the symbol “Mg”. Because the mineral has a high chemical reactivity, it occurs in nature not in elemental but exclusively in cationically bound form – for example, as magnesite (MgCO3), dolomite (MgCO3* Ca-CO3), kieserite (MgSO4* H2O), magnesium chloride (MgCl2), and magnesium bromide (MgBr2). Magnesium compounds can also be detected in seawater – on average, about 15% of seawater salts consist of magnesium compounds.
Magnesium homeostasis – absorption, distribution, and excretion
Resorption
Magnesium is absorbed throughout the small intestine. Under normal conditions, the absorption rate is between 35 and 55% and can be increased to 75% or decreased to 25% depending on the amount of magnesium supplied. Enteric absorption occurs both paracellularly by passive diffusion and transcellularly by a carrier-mediated process – overcoming the cell membrane with the aid of transport proteins. Magnesium is primarily taken up by a specific transporter, the TRPM6 ion channel in the intestinal wall. When the supply of magnesium is high, this transport mechanism is saturated and the amount of magnesium absorbed decreases in percentage. Thus, the extracellular magnesium concentration is kept constant. Conversely, low magnesium intake or a magnesium deficiency state results in an increase in intestinal absorption – in favor of the magnesium level in the extracellular space. When serum magnesium levels are low, parathyroid hormone (PTH), a peptide hormone consisting of 84 amino acids, and calcitriol, the most important metabolically active form of vitamin D, are released in greater amounts. By stimulating magnesium uptake in the small intestine and the transport of the mineral from the intestine into the extracellular space, PTH and calcitriol lead to an increase in the extracellular free magnesium concentration. The absorption or bioavailability of the mineral depends on numerous factors:
- Amount or dose of magnesium supplied.
- Type and solubility of magnesium compounds used – magnesium citrate, chloride, lactate, and aspartate are more available than the poorly absorbable magnesium oxide and sulfate
- Dietary composition – Magnesium from milk is more bioavailable than from cereals, legumes or meat.
- Intestinal motility
- Passage time
- Interactions with other elements
- Supply status of the body
Also of important importance are age, physical activity and fluid intake. For example, magnesium from mineral water is available to about 50%. If magnesium-rich mineral water is supplied in conjunction with a meal, the absorption rate or bioavailability of magnesium increases by an average of 14%.
Distribution
Intracellular Magnesium Magnesium, along with potassium, is one of the most important intracellular elements. About 95% of the total magnesium in the body is intracellular, that is, in the body’s cells. Of this, 50-70 % is localized in bound form – magnesium binds to hydroxyapatite – in the bones. The skeleton is thus the largest store of magnesium. Approximately 28% of the magnesium present intracellularly is stored in the muscles, and the remaining portion of the mineral is stored in the soft tissues. The magnesium present in soft tissues (35%) is bound to ATP, phospholipids, nucleic acids and polyamines by 90%. Approximately 10% is present in ionized, free form. Extracellular magnesium Only 5% of whole-body magnesium is found in the extracellular fluid and less than 1% is found in serum and in the interstitial fluid – fluid located between body cells. The magnesium concentration in serum and plasma, respectively, is about 0.8-1.1 mmol/L. Of this, 32 % is bound to plasma proteins – albumin or globulin – and about 13 % to low-molecular ligands – citrate, phosphate, sulfate or carbonate. 55 % are freely dissolved as magnesium ions. Only the ionized or free magnesium is biologically active. The free magnesium in the intracellular space is regulated within narrow limits by adjusting influx and efflux. If the intracellular magnesium concentration is increased, more magnesium is transported out of the cell – Mg2+ efflux.If there is a drop in the cytosolic level, the magnesium influx into the cell is conversely promoted – Mg2+ influx. The intracellular magnesium concentration can drop, among other things, due to a lack of binding sites – for example, in the case of excessive ATP consumption. Under these circumstances, the term magnesium depletion is used rather than magnesium deficiency. In order for the cytosolic magnesium concentration to return to its normal level, both the magnesium intake must be increased and the synthesis of binding sites must be stimulated. For example, ATP synthesis can be increased by the administration of orotic acid. Orotic acid is an important endogenous substance that is particularly abundant in breast milk. The free extracellular magnesium concentration is kept constant within a very narrow range under physiological conditions by adjusting absorption, excretion, and exchange with skeletal stores with the help of a complex hormonal regulatory system.
Excretion
Free magnesium is excreted predominantly by the kidney. There, the essential mineral is glomerularly filtered and 95 to 97% reabsorbed. Through tubular reabsorption, magnesium is again available to the organism. 3-5 % of the glomerular filtered magnesium (5-8.5 mmol magnesium per day) is excreted with the final urine. The kidney is able to sense changes in extracellular free magnesium concentration via specific sensors. If there is a drop in the serum magnesium level, parathyroid hormone is increasingly produced in the parathyroid cells and subsequently secreted. At the kidney, PTH promotes the expression of 1alpha-hydroxylase and thus the formation of calcitriol. Parathyroid hormone and calcitriol stimulate tubular magnesium reabsorption and inhibit renal magnesium excretion. A decrease in renal magnesium excretion below 4 mmol per day indicates magnesium deficiency. PTH and calcitriol eventually lead to an increase in extracellular free magnesium concentration via increasing tubular magnesium reabsorption and inhibiting renal magnesium excretion. Hypermagnesemia (magnesium excess) causes thyroid C cells, which sense a change in serum magnesium concentration via specific sensors, to synthesize and release increased calcitonin. Calcitonin is a peptide hormone consisting of 32 amino acids. It stimulates renal magnesium excretion. Calcitonin is thus responsible for lowering the extracellular magnesium concentration when serum magnesium levels are elevated. The peptide hormone represents a direct antagonist to the parathyroid hormone. As a result of a high magnesium serum concentration, the secretion of parathormone and the production of calcitriol controlled by it are prevented in parallel with calcitonin release. The result is reduced magnesium absorption in the intestine and diffusion into the extracellular space, inhibited renal tubular reabsorption, and thus increased renal magnesium excretion. Subsequently, the extracellular free magnesium concentration drops and the serum magnesium level normalizes. In addition to calcitonin, renal reabsorption of magnesium can be decreased by aldosterone, ADH, thyroid hormone, growth hormone, and a high intake of calcium.
