Magnesium deficiency is a state of decreased total body magnesium content. The human body contains 21-28 g of magnesium, the majority of which is localised in bone (>53%) and non-muscular tissue (approximately 19%). Hypomagnesaemia (low serum magnesium concentration) is generally defined as serum magnesium <0.75 mmol/L (<1.5 mEq/L).
Serum magnesium level is a poor indicator of the total magnesium content and availability in the body, because only 1% of magnesium is found in the extracellular fluid. There is no simple, rapid, and accurate laboratory test to determine total body magnesium status in humans.
Determination of urinary magnesium level provides an indirect assessment of whole body magnesium content, especially when the urinary value is compared with the serum level.
Magnesium deficiency is usually detected because of the resultant hypomagnesaemia. However, it may also be revealed by the development of clinical symptoms, or associated hypokalaemia or hypocalcaemia.
Calcium competes with magnesium for uptake in the loop of Henle, and an increase in the filtered calcium load can impair magnesium reabsorption. Hypomagnesaemia, in turn, leads to parathyroid hormone (PTH) resistance and a decrease in PTH secretion, both of which lead to hypocalcaemia.
Hypokalaemia is commonly seen in patients with hypomagnesaemia, partly because the associated underlying disorders can produce both these disturbances. However, there is also evidence that hypomagnesaemia can lead to increased renal potassium wasting.
Patients with abnormalities of magnesium homoeostasis typically fall into one of three groups:
Patients with magnesium deficiency (low total body magnesium content) and a resultant hypomagnesaemia (low serum magnesium concentration)
Patients with hypomagnesaemia (low serum magnesium concentration) in the absence of magnesium deficiency (i.e., a normal total body magnesium content)
Patients with magnesium deficiency (low total body magnesium content) but no evidence of hypomagnesaemia (i.e., a normal serum magnesium concentration).
About 60% of magnesium in the serum is free, whereas approximately 33% is bound to proteins, and <7% is bound to citrate, bicarbonate, ATP, and phosphate.
Magnesium status is regulated by the intestines, which control absorption; the kidneys, which control excretion; and bone, which is the major storage site. Absorption and excretion are mediated by the selective magnesium channel TRPM6, whereas magnesium uptake and release from tissues outside the intestines and kidneys is controlled by TRPM7, which has an approximately 60% homology to TRPM6.
Absorption: magnesium absorption is a saturable process that occurs throughout the small and large intestines, with most of the absorption taking place in the colon. The average daily intake of magnesium is approximately 320 mg in men, and 240 mg in women; approximately two-thirds of this amount is eliminated with the faeces, while one third is absorbed and passed into the circulation. Magnesium regulates the expression of TRPM6; a sustained fall in magnesium level results in increased expression, and increased magnesium absorption.
Excretion and reabsorption: the major site of reabsorption is the loop of Henle, although additional reabsorption takes place in the distal convoluted tubule. Approximately 2400 mg/day of magnesium passes through the kidneys, <5% of which is eventually excreted. Since magnesium regulates the expression of TRPM6, a sustained fall in magnesium level results in increased magnesium reabsorption.
Although there is no direct hormonal control of magnesium absorption, excretion, and reabsorption, TRPM6 expression appears to be under oestrogen modulation.
There is normally very little exchange between intracellular and extracellular magnesium. In the acute phase of a fall in magnesium content, intestinal absorption and renal reabsorption both increase. Hormones such as glucagon, catecholamines, and PTH can mobilise magnesium from bone and other tissues. Magnesium, in turn, exhibits negative feedback on catecholamine release. Conversely, hormones such as insulin, antidiuretic hormone (ADH), and thyroid hormone promote magnesium uptake and storage.
Cellular functions of magnesium
Magnesium is a predominantly intracellular ion and is distributed between the nucleus, endoplasmic or sarcoplasmic reticulum, mitochondria, and cytoplasm. Approximately 200 enzymes involved in cellular metabolism and the cell cycle require magnesium as a co-factor, including adenyl cyclase and ATPases. Magnesium is also an important co-factor for potassium and calcium channels, and therefore plays a role in regulating action potentials in cardiac and neural tissues, as well as calcium signalling in a wide range of tissues.
Recommended dietary allowance for magnesium
The recommended dietary allowance for magnesium varies according to age and sex as follows:
Infants (birth to 12 months): 30-75 mg/day
Children/adolescents (1 to 18 years): 80-410 mg/day
Adult females (>18 years): 310-320 mg/day, increased to 310-360 mg/day during pregnancy and lactation
Adult males (>18 years): 400-420 mg/day
- Isolated dietary magnesium deficiency
- Alcohol abuse
- Laxative abuse
- Crohn's disease
- Ulcerative colitis
- Coeliac disease
- Short gut syndrome
- Diabetic ketoacidosis
- Excess of intravenous fluids
- Acute pancreatitis
- Chronic pancreatitis
- Whipple's disease
- Hungry bone syndrome
- Recovery phase of acute tubular necrosis
- Renal tubular acidosis
- Post-obstructive diuresis
- Primary renal magnesium wasting
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