Magnesium deficiency

• Loop and thiazide diuretic use (the most common cause of hypomagnesemia)[18]
• Antibiotics (i.e. aminoglycoside, amphotericin, pentamidine, gentamicin, tobramycin, viomycin) block resorption in the loop of Henle. 30% of patients using these antibiotics have hypomagnesemia.[19]
• Long term, high dosage use of proton-pump inhibitors such as omeprazole[20][21]
• Other drugs
  • Digitalis, displaces magnesium into the cell. Digitalis causes an increased intracellular concentration of sodium, which in turn increases intracellular calcium by passively increasing the action of the sodium-calcium exchanger in the sarcolemma. The increased intracellular calcium gives a positive inotropic effect.[18]
  • Adrenergics, displace magnesium into the cell
  • Cisplatin, stimulates kidney excretion
  • Ciclosporin, stimulates kidney excretion
  • Mycophenolate mofetil

• Gitelman-like diseases, which include the syndromes caused by genetic mutations in SLC12A3, CLNCKB,[22] BSND, KCNJ10, FXYD2, HNF1B or PCBD1. In these diseases, the hypomagnesemia is accompanied by other defects in electrolyte handling such as hypocalciuria and hypokalemia. The genes involved in this group of diseases all encode proteins that are involved in reabsorbing electrolytes (including magnesium) in the distal convoluted tubule of the kidney.[10]
• Hypercalciuric hypomagnesemic syndromes, which encompass the syndromes caused by mutations in CLDN16, CLDN19, CASR or CLCNKB. In these diseases, reabsorption of divalent cations (such as magnesium and calcium) in the thick ascending limb of Henle's loop of the kidney is impaired. This results in loss of magnesium and calcium in the urine.[10]
• Mitochondriopathies, especially mutations in the mitochondrial tRNAs MT-TI or MT-TF.[23] Mutations in SARS2, or mitochondrial DNA deletions as seen with Kearns-Sayre syndrome, can also cause hypomagnesemia.[10]
• Other genetic causes of hypomagnesemia, such as mutations in TRPM6, CNNM2, EGF, EGFR, KCNA1 or FAM111A. Many of the proteins encoded by these genes play a role in the transcellular absorption of magnesium in the distal convoluted tubule.[10]

• Insufficient selenium,[24] vitamin D or sunlight exposure, or vitamin B6.[25]
• Gastrointestinal causes: the distal digestive tract secretes high levels of magnesium. Therefore, secretory diarrhea can cause hypomagnesemia. Thus, Crohn's disease, ulcerative colitis, Whipple's disease and celiac sprue can all cause hypomagnesemia.
• Postobstructive diuresis, diuretic phase of acute tubular necrosis (ATN) and kidney transplant.[26]

• Chronic alcoholism: Alcohol intake leads to enhanced diuresis of electrolytes. Chronic consumption leads to the depletion of body stores of magnesium.[27][28][29][30]
• Acute myocardial infarction: within the first 48 hours after a heart attack, 80% of patients have hypomagnesemia. This could be the result of an intracellular shift because of an increase in catecholamines.
• Malabsorption
• Acute pancreatitis
• Fluoride poisoning
• Massive transfusion (MT) is a lifesaving treatment of hemorrhagic shock, but can be associated with significant complications.[31]

Potassium channel efflux is inhibited by magnesium. Thus hypomagnesemia results in an increased excretion of potassium in kidney, resulting in a hypokalaemia. This condition is believed to occur secondary to the decreased normal physiologic magnesium inhibition of the ROMK channels in the apical tubular membrane.[32]

In this light, hypomagnesemia is frequently the cause of hypokalaemic patients failing to respond to potassium supplementation. Thus, clinicians should ensure that both magnesium and potassium is replaced when deficient. Patients with diabetic ketoacidosis should have their magnesium levels monitored to ensure that the serum loss of potassium, which is driven intracellularly by insulin administration, is not exacerbated by additional urinary losses.

Release of calcium from the sarcoplasmic reticulum is inhibited by magnesium. Thus hypomagnesemia results in an increased intracellular calcium level. This inhibits the release of parathyroid hormone, which can result in hypoparathyroidism and hypocalcemia. Furthermore, it makes skeletal and muscle receptors less sensitive to parathyroid hormone.[33]

Magnesium is needed for the adequate function of the Na⁺/K⁺-ATPase pumps in cardiac myocytes, the muscles cells of the heart. A lack of magnesium inhibits reuptake of potassium, causing a decrease in intracellular potassium. This decrease in intracellular potassium results in a tachycardia.

Magnesium has an indirect antithrombotic effect upon platelets and endothelial function. Magnesium increases prostaglandins, decreases thromboxane, and decreases angiotensin II, microvascular leakage, and vasospasm through its function similar to calcium channel blockers. Convulsions are the result of cerebral vasospasm. The vasodilatatory effect of magnesium seems to be the major mechanism.

Magnesium exerts a bronchodilatatory effect, probably by antagonizing calcium-mediated bronchoconstriction.[34]

• reducing electrical excitation
• modulating release of acetylcholine
• antagonising N-methyl-D-aspartate (NMDA) glutamate receptors, an excitatory neurotransmitter of the central nervous system and thus providing neuroprotection from excitoxicity.

Magnesium deficiency is frequently observed in people with type 2 diabetes mellitus, with an estimated prevalence ranging between 11.0 and 47.7%.[35] Magnesium deficiency is strongly associated with high glucose and insulin resistance, which indicate that it is common in poorly controlled diabetes.[36] Patients with type 2 diabetes and a magnesium deficiency have a higher risk of heart failure, atrial fibrillation and microvascular complications.[37] Oral magnesium supplements has been demonstrated to improve insulin sensitivity and lipid profile.[38][39][40] A 2016 meta-analysis not restricted to diabetic subjects found that increasing dietary magnesium intake, while associated with a reduced risk of stroke, heart failure, diabetes, and all-cause mortality, was not clearly associated with lower risk of coronary heart disease (CHD) or total cardiovascular disease (CVD).[41]

A 2021 study on blood from 4,400 diabetic patients over 6 to 11 years reported that "People with higher levels of magnesium in the blood were found to have a significantly lower risk of cardiovascular disease", and also of diabetic foot and diabetic retinopathy. The researchers, however, stated that "we have [not] demonstrated that magnesium supplements work. Further research is needed."[42]

Magnesium is abundant in nature. It can be found in green vegetables, chlorophyll (chloroplasts), cocoa derivatives, nuts, wheat, seafood, and meat. It is absorbed primarily in the duodenum of the small intestine. The rectum and sigmoid colon can absorb magnesium. Forty percent of dietary magnesium is absorbed. Hypomagnesemia stimulates and hypermagnesemia inhibits this absorption.

The body contains 21–28 grams of magnesium (0.864–1.152 mol). Of this, 53% is located in bone, 19% in non-muscular tissue, and 1% in extracellular fluid. For this reason, blood levels of magnesium are not an adequate means of establishing the total amount of available magnesium.

The majority of serum magnesium is bound to chelators, including proteins and citrate. Roughly 33% is bound to proteins, and 5–10% is not bound. This "free" magnesium is essential in regulating intracellular magnesium. Normal plasma Mg is 1.7–2.3 mg/dL (0.69–0.94 mmol/L).

The kidneys regulate the serum magnesium. About 2400 mg of magnesium passes through the kidneys daily, of which 5% (120 mg) is excreted through urine. The loop of Henle is the major site for magnesium homeostasis, and 60% is reabsorbed.

Magnesium homeostasis comprises three systems: kidney, small intestine, and bone. In the acute phase of magnesium deficiency there is an increase in absorption in the distal small intestine and tubular resorption in the kidneys. When this condition persists, serum magnesium drops and is corrected with magnesium from bone tissue. The level of intracellular magnesium is controlled through the reservoir in bone tissue.

The electrocardiogram (ECG) change may show a tachycardia with a prolonged QT interval.[45] Other changes may include prolonged PR interval, ST segment depression, flipped T waves, and long QRS duration.[1]

Food sources of magnesium include leafy green vegetables, beans, nuts, and seeds.[50]