Magnesium deficiency

Magnesium deficiency
Other names: Hypomagnesia, hypomagnesemia
Magnesium
SpecialtyEndocrinology
SymptomsTremor, poor coordination, nystagmus, seizures[1]
ComplicationsSeizures, cardiac arrest (torsade de pointes), low potassium[1]
CausesAlcoholism, starvation, diarrhea, increased urinary loss, poor absorption from the intestines, certain medications[1][2]
Diagnostic methodBlood levels < 0.6 mmol/L (1.46 mg/dL)[1]
TreatmentMagnesium salts[2]
FrequencyRelatively common (hospitalized people)[2]

Magnesium deficiency is an electrolyte disturbance in which there is a low level of magnesium in the body.[3] Symptoms include tremor, poor coordination, muscle spasms, loss of appetite, personality changes, and nystagmus.[1][2] Complications may include seizures or cardiac arrest such as from torsade de pointes.[1] Those with low magnesium often have low potassium.[1]

Causes include low dietary intake, alcoholism, diarrhea, increased urinary loss, poor absorption from the intestines, and diabetes mellitus.[1][4][5] A number of medications may also cause low magnesium, including proton pump inhibitors (PPIs) and furosemide.[2] The diagnosis is typically based on finding low blood magnesium levels (hypomagnesemia).[6] Normal magnesium levels are between 0.6-1.1 mmol/L (1.46–2.68 mg/dL) with levels less than 0.6 mmol/L (1.46 mg/dL) defining hypomagnesemia.[1] Specific electrocardiogram (ECG) changes may be seen.[1]

Treatment is with magnesium either by mouth or intravenously.[2] For those with severe symptoms, intravenous magnesium sulfate may be used.[1] Associated low potassium or low calcium should also be treated.[2] The condition is relatively common among people in hospital.[2]

Signs and symptoms

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.[7] Magnesium plays an important role in carbohydrate metabolism and its deficiency may worsen insulin resistance, a condition that often precedes diabetes, or may be a consequence of insulin resistance.[8]

People being treated on an intensive care unit (ICU) who have a low magnesium level may have a higher risk of requiring mechanical ventilation, and death.[9]

Causes

Magnesium deficiency may result from gastrointestinal or kidney causes. Gastrointestinal causes include inadequate 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.[10]

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.[11][12]

About 57% of the US population does not meet the US RDA for dietary intake of magnesium.[13] The kidneys are very efficient at maintaining body levels; however, if the diet is deficient, or certain medications such as proton-pump inhibitors are used,[14] or in chronic alcoholism,[15] 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

  • Loop and thiazide diuretic use (the most common cause of hypomagnesemia)[16]
  • 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 use of proton-pump inhibitors such as omeprazole[17][18]
  • 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.[16]
    • Adrenergics, displace magnesium into the cell
    • Cisplatin, stimulates kidney excretion
    • Ciclosporin, stimulates kidney excretion
    • Mycophenolate mofetil

Genetics

  • Gitelman-like diseases, which include the syndromes caused by genetic mutations in SLC12A3, CLNCKB,[19] 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.[7]
  • 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.[7]
  • Mitochondriopathies, such as caused by mutations in SARS2, MT-TI or as seen with Kearns-Sayre syndrome.[7]
  • 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.[7]

Metabolic abnormalities

Other

  • 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.[21]

Pathophysiology

Magnesium is a co-factor in over 300 functions in the body regulating many kinds of biochemical reactions.[19] It is involved in protein synthesis, muscle and nerve functioning, bone development, energy production, the maintenance of normal heart rhythm, and the regulation of glucose and blood pressure, among other important roles.[15] Low magnesium intake over time can increase the risk of illnesses, including high blood pressure and heart disease, diabetes mellitus type 2, osteoporosis, and migraines.[15]

There is a direct effect on sodium (Na), potassium (K), and calcium (Ca) channels. Magnesium has several effects:

Potassium

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.[22]

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.

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.[23]

Arrhythmia

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.

Pre-eclampsia

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.

Asthma

Magnesium exerts a bronchodilatatory effect, probably by antagonizing calcium-mediated bronchoconstriction.[24]

Neurological effects

  • 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.

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.

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.

Diagnosis

Magnesium deficiency is not easy to directly measure.[25] Typically the diagnosis is based on finding low blood magnesium levels (hypomagnesemia).[6] Specifically by finding a plasma magnesium concentration of less than 0.6 mmol/l (1.46 mg/dl).[1] Severe disease generally has a level of less than 0.50 mmol/l (1.25 mg/dl).[2]

Magnesium deficiency (or depletion) refers to low total body levels of magnesium which is usually determined by finding low blood levels (hypomagnesemia). Hypomagnesemia refers only to blood levels of magnesium.[26] Either of magnesium deficiency and hypomagnesemia can be present without the other.[25]

Electrocardiogram

The electrocardiogram (ECG) change may show a tachycardia with a prolonged QT interval.[27] Other changes may include prolonged PR interval, ST segment depression, flipped T waves, and long QRS duration.[1]

Treatments

Treatment of hypomagnesemia 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.[28]

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.[29][30] Magnesium citrate has been reported as more bioavailable than oxide or amino-acid chelate forms.[31]

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.[32]

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.[33]

Plants

A plant with magnesium deficiency

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.[34] Excess potassium, generally due to fertilizers, further aggravates the stress from magnesium deficiency,[35] as does aluminium toxicity.[36]

Magnesium has an important role in photosynthesis because it forms the central atom of chlorophyll.[34] Therefore, without sufficient amounts of magnesium, plants begin to degrade the chlorophyll in the old leaves. This causes the main symptom of magnesium deficiency, interveinal chlorosis, or yellowing between leaf veins, which stay green, giving the leaves a marbled appearance. Due to magnesium's mobile nature, the plant will first break down chlorophyll in older leaves and transport the Mg to younger leaves which have greater photosynthetic needs. Therefore, the first sign of magnesium deficiency is the chlorosis of old leaves which progresses to the young leaves as the deficiency progresses.[37] 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 lead to a decrease in 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.[34] After prolonged magnesium deficiency, necrosis and dropping of older leaves occurs. Plants deficient in magnesium also produce smaller, woodier fruits.

Magnesium deficiency in plants may be confused with zinc or chlorine deficiencies, viruses, or natural aging, since all have similar symptoms. Adding Epsom salts (as a solution of 25 grams per liter or 4 oz per gal) or crushed dolomitic limestone to the soil can rectify magnesium deficiencies. An organic treatment is to apply compost mulch, which can prevent leaching during excessive rainfall and provide plants with sufficient amounts of nutrients, including magnesium.[38]

See also

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Soar, J; Perkins, GD; Abbas, G; Alfonzo, A; Barelli, A; Bierens, JJ; Brugger, H; Deakin, CD; Dunning, J; Georgiou, M; Handley, AJ; Lockey, DJ; Paal, P; Sandroni, C; Thies, KC; Zideman, DA; Nolan, JP (October 2010). "European Resuscitation Council Guidelines for Resuscitation 2010 Section 8. Cardiac arrest in special circumstances: Electrolyte abnormalities, poisoning, drowning, accidental hypothermia, hyperthermia, asthma, anaphylaxis, cardiac surgery, trauma, pregnancy, electrocution". Resuscitation. 81 (10): 1400–33. doi:10.1016/j.resuscitation.2010.08.015. PMID 20956045.
  2. 1 2 3 4 5 6 7 8 9 10 "Hypomagnesemia". Merck Manuals Professional Edition. Archived from the original on 19 October 2018. Retrieved 27 October 2018.
  3. ↑ "Definition of Magnesium Deficiency". MedicineNet.com. Archived from the original on 31 May 2014. Retrieved 31 May 2014.
  4. ↑ de Baaij JH, Hoenderop JG, Bindels RJ (January 2015). "Magnesium in man: implications for health and disease". Physiol. Rev. 95 (1): 1–46. CiteSeerX 10.1.1.668.9777. doi:10.1152/physrev.00012.2014. PMID 25540137.
  5. ↑ Gommers LM, Hoenderop JG, Bindels RJ, de Baaij JH (January 2016). "Hypomagnesemia in Type 2 Diabetes: A Vicious Circle?". Diabetes. 65 (1): 3–13. doi:10.2337/db15-1028. PMID 26696633.
  6. 1 2 Goldman, Lee; Schafer, Andrew I. (2015). Goldman-Cecil Medicine E-Book. Elsevier Health Sciences. p. 775. ISBN 9780323322850. Archived from the original on 2018-10-10. Retrieved 2018-10-10.
  7. 1 2 3 4 5 Viering, Daan H. H. M.; Baaij, Jeroen H. F. de; Walsh, Stephen B.; Kleta, Robert; Bockenhauer, Detlef (2016-05-27). "Genetic causes of hypomagnesemia, a clinical overview". Pediatric Nephrology. 32 (7): 1123–1135. doi:10.1007/s00467-016-3416-3. ISSN 0931-041X. PMC 5440500. PMID 27234911.
  8. ↑ Kobrin, SM; Goldfarb, S (Nov 1990). "Magnesium deficiency". Seminars in Nephrology. 10 (6): 525–35. PMID 2255809.
  9. ↑ Upala, Sikarin; Jaruvongvanich, Veeravich; Wijarnpreecha, Karn; Sanguankeo, Anawin (24 March 2016). "Hypomagnesemia and mortality in patients admitted to intensive care unit: a systematic review and meta-analysis". QJM. 109 (7): 453–459. doi:10.1093/qjmed/hcw048. PMID 27016536.
  10. ↑ DiNicolantonio JJ, O'Keefe JH, Wilson W (2018). "Subclinical magnesium deficiency: a principal driver of cardiovascular disease and a public health crisis". Open Heart. 5 (1): e000668. doi:10.1136/openhrt-2017-000668. PMC 5786912. PMID 29387426.
  11. ↑ Agus, Zalman S. (July 1999). "Hypomagnesemia". Journal of the American Society of Nephrology. 10 (7): 1616–1622. Archived from the original on 2016-12-10. Retrieved 2018-10-11.
  12. ↑ ZALMAN S. AGUS (1999). "Hypomagnesemia". Journal of the American Society of Nephrology. 10 (7): 1616.
  13. ↑ "Nutrient Intakes Percent of population 2 years old and over with adequate intakes based on average requirement". Community Nutrition Mapping Project. 2009-07-29. Archived from the original on 2016-08-04. Retrieved 2012-02-11.
  14. ↑ "FDA Drug Safety Communication: Low magnesium levels can be associated with long-term use of Proton Pump Inhibitor drugs (PPIs)". fda.gov. F.D.A. U.S. Food and Drug Administration. Archived from the original on 5 March 2011. Retrieved 8 November 2014.
  15. 1 2 3 "Magnesium: Fact Sheet for Health Professionals". nih.gov. National Institutes of Health. Archived from the original on 8 February 2018. Retrieved 8 November 2014.
  16. 1 2 Whang R, Hampton EM, Whang DD (1994). "Magnesium homeostasis and clinical disorders of magnesium deficiency". Ann Pharmacother. 28 (2): 220–6. doi:10.1177/106002809402800213. PMID 8173141.
  17. ↑ "Archive copy". Archived from the original on 2017-03-05. Retrieved 2019-12-16.{{cite web}}: CS1 maint: archived copy as title (link)
  18. ↑ Sheen, E; Triadafilopoulos, G (April 2011). "Adverse effects of long-term proton pump inhibitor therapy". Digestive Diseases and Sciences. 56 (4): 931–50. doi:10.1007/s10620-010-1560-3. PMID 21365243.
  19. 1 2 al-Ghamdi SM, Cameron EC, Sutton RA (1994). "Magnesium deficiency: pathophysiologic and clinical overview". Am. J. Kidney Dis. 24 (5): 737–52. doi:10.1016/s0272-6386(12)80667-6. PMID 7977315.
  20. ↑ Chareonpong-Kawamoto N, Yasumoto K (1995). "Selenium deficiency as a cause of overload of iron and unbalanced distribution of other minerals". Biosci. Biotechnol. Biochem. 59 (2): 302–6. doi:10.1271/bbb.59.302. PMID 7766029.
  21. ↑ Sihler, KC; Napolitano, LM (January 2010). "Complications of massive transfusion". Chest. 137 (1): 209–20. doi:10.1378/chest.09-0252. PMID 20051407.
  22. ↑ Huang CL, Kuo E (2007). "Mechanism of Hypokalemia in Magnesium Deficiency". J Am Soc Nephrol. 18 (10): 2649–2652. doi:10.1681/ASN.2007070792. PMID 17804670.
  23. ↑ Agus, Zalman (July 1999). "Hypomagnesemia". Journal of the American Society of Nephrology. 10 (7): 1616–1622. PMID 10405219. Archived from the original on 2016-12-10. Retrieved 2018-10-11.
  24. ↑ Mills R, Leadbeater M, Ravalia A (1997). "Intravenous magnesium sulphate in the management of refractory bronchospasm in a ventilated asthmatic". Anaesthesia. 52 (8): 782–5. doi:10.1111/j.1365-2044.1997.176-az0312.x. PMID 9291766.
  25. 1 2 Swaminathan, R (2003). "Magnesium Metabolism and its Disorders". Clin Biochem Rev. 24 (2): 47–66. PMC 1855626. PMID 18568054.
  26. ↑ "Definition of Hypomagnesemia". MedicineNet.com. Archived from the original on 31 May 2014. Retrieved 31 May 2014.
  27. ↑ Famularo G1, Gasbarrone L, Minisola G. Hypomagnesemia and proton-pump inhibitors. Expert Opin Drug Saf. 2013 Sep;12(5):709-16.
  28. ↑ Durlach J, Durlach V, Bac P, Bara M, Guiet-Bara A (1994). "Magnesium and therapeutics". Magnes Res. 7 (3–4): 313–28. PMID 7786695.
  29. ↑ Firoz M, Graber M (2001). "Bioavailability of US commercial magnesium preparations". Magnes Res. 14 (4): 257–62. PMID 11794633.
  30. ↑ Lindberg JS, Zobitz MM, Poindexter JR, Pak CY (1990). "Magnesium bioavailability from magnesium citrate and magnesium oxide". J Am Coll Nutr. 9 (1): 48–55. doi:10.1080/07315724.1990.10720349. PMID 2407766.
  31. ↑ Walker AF, Marakis G, Christie S, Byng M (2003). "Mg citrate found more bioavailable than other Mg preparations in a randomised, double-blind study". Magnes Res. 16 (3): 183–91. PMID 14596323. Archived from the original on 2021-08-28. Retrieved 2018-10-11.
  32. ↑ "Abridged List Ordered by Nutrient Content in Household Measure Source: USDA National Nutrient Database for Standard Reference Legacy (2018) Nutrients: Magnesium, Mg(mg)" (PDF). United States Department of Agriculture. Archived (PDF) from the original on October 17, 2020. Retrieved May 20, 2020.
  33. ↑ Hirschfelder, A. D.; Haury, V. G. (1934). "Clinical Manifestations of High and Low Plasma Magnesium; Dangers of Epsom Salt Purgation in Nephritis". Journal of the American Medical Association. 102 (14): 1138. doi:10.1001/jama.1934.02750140024010.
  34. 1 2 3 Norman P.A. Huner; William Hopkins (2008-11-07). "3 & 4". Introduction to Plant Physiology 4th Edition. John Wiley & Sons, Inc. ISBN 978-0-470-24766-2.
  35. ↑ Ding Y.; Chang C.; Luo W. "High Potassium Aggravates the Oxidative Stress Induced by Magnesium Deficiency in Rice Leaves". Pedosphere. Vol. 18, no. 3. pp. 316–327.
  36. ↑ Merhaut, D.J. (2006). "Magnesium". In Barker A.V.; Pilbeam D.J. (ed.). Handbook of plant nutrition. Boca Raton: CRC Press. p. 154. ISBN 9780824759049.{{cite book}}: CS1 maint: multiple names: editors list (link)
  37. ↑ Hermans C.; Vuylsteke F.; Coppens F. "Systems Analysis of the responses to long-term magnesium deficiency and restoration in Arabidopsis thaliana". New Phytologist. Vol. 187. pp. 132–144.
  38. ↑ "Problem Solving: Magnesium Deficiency". Archived from the original on 2011-11-05. Retrieved 2018-10-10.
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