Magnesium deficiency

Magnesium deficiency is an

People being treated in an intensive care unit (ICU) who have a low magnesium level may have a higher risk of requiring mechanical ventilation, and death.^[12]

Causes

Magnesium deficiency may result from gastrointestinal or kidney causes. Gastrointestinal causes include low dietary intake of magnesium, reduced gastrointestinal absorption or increased gastrointestinal loss due to rapid gastrointestinal transits. Kidney causes involve increased excretion of magnesium. Poor dietary intake of magnesium has become an increasingly important factor – many people consume diets high in refined foods such as white bread and polished rice which have been stripped of magnesium-rich plant fiber.^[13]

Magnesium deficiency is not uncommon in hospitalized patients. Up to 12% of all people admitted to hospital, and as high as 60–65% of people in an intensive care unit, have hypomagnesemia.^[14]

About 57% of the US population does not meet the US RDA for dietary intake of magnesium.^[15] The kidneys are very efficient at maintaining body levels; however, if the diet is deficient, or certain medications such as diuretics or proton pump inhibitors are used,^[16] or in chronic alcoholism,^[17] levels may drop.

Low levels of magnesium in blood may be due to not enough magnesium in the diet, the intestines not absorbing enough magnesium, or the kidneys excreting too much magnesium. Deficiencies may be due to the following conditions:

Medications

• thiazide diuretic use (the most common cause of hypomagnesemia)^[18]
• Antibiotics (i.e.
  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
  • inotropic effect.^[18]
  • Adrenergics
    , displace magnesium into the cell
  • Cisplatin, stimulates kidney excretion
  • Ciclosporin, stimulates kidney excretion
  • Mycophenolate mofetil

Genetics

• 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]
• 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
  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
  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]

Pathophysiology

Magnesium is a co-factor in over 300 functions in the body regulating many kinds of biochemical reactions.

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. ^{[citation needed]}

Calcium

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.^[14]

Arrhythmia

Magnesium is needed for the adequate function of the

Magnesium exerts a bronchodilatatory effect, probably by antagonizing calcium-mediated bronchoconstriction.[33]

Neurological effects

• reducing electrical excitation
• modulating release of acetylcholine
• antagonising N-methyl-D-aspartate (
  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%.[34] Magnesium deficiency is strongly associated with high glucose and insulin resistance, which indicate that it is common in poorly controlled diabetes.^[35] Patients with type 2 diabetes and a magnesium deficiency have a higher risk of heart failure, atrial fibrillation and microvascular complications.^[36] Oral magnesium supplements has been demonstrated to improve insulin sensitivity and lipid profile.^[37][38][39] 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).^[40]

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."^[41]

Homeostasis

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. ^{[citation needed]}

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.^{[citation needed]} For this reason, blood levels of magnesium are not an adequate means of establishing the total amount of available magnesium.^{[citation needed]}

The majority of

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.

Diagnosis

Magnesium deficiency or depletion is a low total body level of magnesium; it is not easy to measure directly.^[42] Typically the diagnosis is based on finding hypomagnesemia, a low blood magnesium level,^[43] which often reflects low body magnesium;^[6] however, magnesium deficiency can be present without hypomagnesemia, and vice versa.^[42] A plasma magnesium concentration of less than 0.6 mmol/L (1.46 mg/dL) is considered to be hypomagnesemia;^[1] severe disease generally has a level of less than 0.50 mmol/L (1.25 mg/dL).^[2]

Electrocardiogram

The

Treatment of magnesium deficiency depends on the degree of deficiency and the clinical effects. Replacement by mouth is appropriate for people with mild symptoms, while intravenous replacement is recommended for people with severe effects.^[45]

Numerous oral

Intravenous magnesium sulfate (MgSO₄) can be given in response to heart arrhythmias to correct for hypokalemia, preventing pre-eclampsia, and has been suggested as having a potential use in asthma.^[1]

Food

Food sources of magnesium include leafy green vegetables, beans, nuts, and seeds.^[49]

Epidemiology

The condition is relatively common among people in hospital.^[2]

History

Magnesium deficiency in humans was first described in the medical literature in 1934.^[50]

Plants

Magnesium deficiency is a detrimental plant disorder that occurs most often in strongly acidic, light, sandy soils, where magnesium can be easily leached away. Magnesium is an essential macronutrient constituting 0.2-0.4% of plants' dry matter and is necessary for normal plant growth.^[51] Excess potassium, generally due to fertilizers, further aggravates the stress from magnesium deficiency,^[52] as does aluminium toxicity.^[53]

Magnesium has an important role in

• Magnesium in biology
• Hypermagnesemia, high level of magnesium in blood

References