Magnesium deficiency

Deficiency of magnesium can cause tiredness, generalized weakness, muscle cramps, abnormal heart rhythms, increased irritability of the nervous system with tremors, paresthesias, palpitations, low potassium levels in the blood, hypoparathyroidism which might result in low calcium levels in the blood, chondrocalcinosis, spasticity and tetany, migraines, epileptic seizures, basal ganglia calcifications and in extreme and prolonged cases coma, intellectual disability or death. Magnesium deficiency is strongly associated with and appears to contribute to obesity, insulin resistance, metabolic syndrome, and type 2 diabetes, although the causal mechanism is not fully understood. ==Causes==

Magnesium deficiency may result from gastrointestinal or kidney causes. Gastrointestinal causes include low dietary magnesium intake, 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. Magnesium deficiency is common 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 (ICU), have hypomagnesemia. About 57% of the US population does not meet the US RDA for dietary magnesium intake. 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, or in chronic alcoholism, • Antibiotics (i.e. aminoglycoside, amphotericin, pentamidine, gentamicin, tobramycin, viomycin) block resorption in the loop of Henle. 30% of patients using these antibiotics have hypomagnesemia, • Long term, high dosage use of proton-pump inhibitors such as omeprazole, • 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, Mutations in SARS2, or mitochondrial DNA deletions as seen with Kearns-Sayre syndrome, can also cause hypomagnesemia, vitamin D or sunlight exposure, or vitamin B6, • 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, Other • Chronic alcoholism: Alcohol intake leads to enhanced diuresis of electrolytes, possibly due to alcohol-induced kidney tubular cell damage. Hypomagnesemia is the most common electrolyte abnormality in those with chronic alcoholism. ==Pathophysiology==

Magnesium is ubiquitous in the human body as well as being present in all living organisms and the ion is a known co-factor in over 300 known enzymatic reactions including DNA and RNA replication, protein synthesis, acting as an essential co-factor of ATP during its phosphorylation via ATPase. It is also extensively involved in intracellular signalling. 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. 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. Neurological effects • Reducing electrical excitation, • Modulating release of acetylcholine, • GABAA receptor agonism, • Antagonising N-methyl-D-aspartate (NMDA) glutamate receptors, an excitatory neurotransmitter of the central nervous system and thus providing neuroprotection from excitotoxicity. Diabetes mellitus Magnesium deficiency is frequently observed in people with type 2 diabetes mellitus, with an estimated prevalence ranging between 11 and 48%. Magnesium deficiency is strongly associated with high glucose and insulin resistance, which indicate that it is common in poorly controlled diabetes. Patients with type 2 diabetes and a magnesium deficiency have a higher risk of heart failure, atrial fibrillation, and microvascular complications. Oral magnesium supplements has been demonstrated to improve insulin sensitivity and lipid profile. 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). Homeostasis Magnesium-rich foods include cereals, green vegetables (with magnesium being a main component of chlorophyll), beans, and nuts. It is absorbed primarily in the small intestine via paracellular transport; passing between intestinal cells. Magnesium absorption in the large intestine is mediated by the transporters TRPM6 and TRPM7. Therefore, normal plasma levels of magnesium may sometimes be seen despite a person being in a state of magnesium deficiency and plasma magnesium levels may underestimate the level of deficiency. Plasma magnesium levels may more accurately reflect magnesium stores when consideration is also given to urinary magnesium losses and oral magnesium intake. Inside cells, 90-95% of magnesium is bound to ligands, including ATP, ADP, citrate, other proteins, and nucleic acids. In the plasma, 30% of magnesium is bound to proteins via free fatty acids; therefore, elevated levels of free fatty acids are associated with hypomagnesemia and a possible risk of cardiovascular disease. The kidneys regulate magnesium levels by reabsorbing magnesium from the tubules. In the proximal tubule (at the beginning of the nephron, the functional unit of the kidney) 20% of magnesium is reabsorbed via paracellular transport with claudin 2 and claudin 12 forming channels to allow for reabsorption. 70% of magnesium is reabsorbed in the thick ascending limb of the loop of Henle where claudins 16 and 19 form the channels to allow for reabsorption. In the distal convoluted tubule, 5-10% of magnesium is reabsorbed transcellularly (through the cells) via the transporters TRPM6 and TRPM7. Epidermal growth factor and insulin activate TRPM6 and 7 and increase magnesium levels via increased renal reabsorption. ==Diagnosis==

Magnesium deficiency or depletion is a low total body level of magnesium; it is not easy to measure directly. which often reflects low body magnesium; A plasma magnesium concentration of less than 0.6 mmol/L (1.46 mg/dL) is considered to be hypomagnesemia; Other changes may include prolonged PR interval, ST segment depression, flipped T waves, and long QRS duration. ==Treatments==

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 symptoms. Numerous oral magnesium preparations are available. In two trials of magnesium oxide, one of the most common forms in magnesium dietary supplements because of its high magnesium content per weight, was less bioavailable than magnesium citrate, chloride, lactate, or aspartate. Amino-acid chelate was also less bioavailable. 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 potential use in asthma. ==Epidemiology==

Hypomagnesemia may be seen in 3-10% of the general population. In population-based cohort studies, chronic magnesium deficiency was associated with an increased risk of cardiovascular death and overall death. ==History==

Magnesium deficiency in humans was first described in the medical literature in 1934. ==Plants==

Magnesium deficiency is a detrimental plant disorder that usually occurs 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. Excess potassium, generally due to fertilizers, further aggravates the stress from magnesium deficiency, as does aluminium toxicity. Magnesium has an important role in photosynthesis because it forms the central atom of chlorophyll. Magnesium also acts as an activator for many critical enzymes, including ribulosebisphosphate carboxylase (RuBisCO) and phosphoenolpyruvate carboxylase (PEPC), both essential enzymes in carbon fixation. Thus, low amounts of Mg decrease photosynthetic and enzymatic activity within the plants. Magnesium is also crucial in stabilizing ribosome structures; hence, a lack of magnesium causes depolymerization of ribosomes, leading to premature aging of the plant. == See also ==