Magnesium deficiency

Magnesium deficiency
Synonyms Hypomagnesia, hypomagnesemia
Magnesium
Specialty Endocrinology

Magnesium deficiency is an electrolyte disturbance in which there is a low level of magnesium in the body. It can result in numerous symptoms.[1] Symptoms include tremor, nystagmus, seizures, and cardiac arrest including torsade de pointes.[2]

Causes include alcoholism, starvation, diarrhea, increased urinary loss, and poor absorption from the intestines.[2] The diagnosis is typically based on finding low blood magnesium levels (hypomagnesemia).[3] Normal magnesium levels are between 1.46–2.68 mg/dL (0.6-1.1 mmol/L) with levels less than 1.46 mg/dL (0.6 mmol/L) defining hypomagnesemia.[2] Specific electrocardiogram (ECG) changes may be seen.[2]

Treatment is generally by increasing of magnesium in diet or supplements either by mouth or intravenously. For those with severe disease intravenous magnesium sulfate may be used.[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.[4] 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.[5]

People being treated on an intensive care unit who have a low magnesium level may have a higher risk of requiring mechanical ventilation, and death.[6]

Causes

Magnesium deficiency is not uncommon in hospitalized patients. Elevated levels of magnesium (hypermagnesemia), however, are nearly always caused by a medical treatment. Up to 12 percent of all people admitted to hospital and as high as 60–65% of people in the intensive care unit (ICU) have hypomagnesemia.[7][8] Hypomagnesemia is probably underdiagnosed, as testing for serum magnesium levels is not routine.

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

Drugs

Medications

Genetic causes

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.[14]

Pathophysiology

Magnesium is a co-factor in over 300 functions in the body regulating many kinds of biochemical reactions.[12] 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.[16]

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.[17]

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.[18]

Neurological effects

  • reducing electrical excitation
  • modulating release of acetylcholine
  • antagonizing 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, 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.

In terms of serum magnesium, the majority is bound to chelators, including {removed ATP and ADP which are not present in serum at significant levels and therefore cannot be significant chelators of magnesium in serum}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.[19] Typically the diagnosis is based on finding low blood magnesium levels (hypomagnesemia).[3] Specifically by finding a plasma magnesium concentration of less than 0.6 mmol/L (1.46 mg/dl).[2] Since most magnesium is inside cells, occationally a body deficit can be present with a normal plasma concentration.

The ECG may show a tachycardia with a prolonged QT interval, which has been noted in proton pump inhibitor-associated hypomagnesemia.[20]

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.[21]

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.[22][23] Magnesium citrate has been reported as more bioavailable than oxide or amino-acid chelate forms.[24]

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.[2]

Food

Food sources of magnesium include leafy green vegetables, soybeans, nuts, and fruits and egg [15]

Epidemiology

57% of the US population does not meet the US RDA for dietary intake of magnesium.[25] The kidneys are very efficient at maintaining body levels, except in cases where the diet is deficient due to the use of certain medications such as proton-pump inhibitors[26] or chronic alcoholism.[15]

History

Magnesium deficiency in humans was first described in the medical literature in 1934.[27]

Terminology

Magnesium deficiency (or depletion) refers to low total body levels of magnesium which is usually determined by finding low blood levels (hypomagnesemia). Magnesium deficiency encompasses a broader scope, and includes disorders of magnesium metabolism and low intracellular storage. Hypomagnesemia refers only to blood levels of magnesium.[28] Magnesium deficiency can be present without hypomagnesemia, and hypomagnesemia can be present without magnesium deficiency.[19] As a disorder of metabolism, magnesium deficiency can be much harder to treat than hypomagnesemia.

In 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.[29] Excess potassium, generally due to fertilizers, further aggravates the stress from magnesium deficiency,[30] as does aluminium toxicity.[31]

Magnesium has an important role in photosynthesis because it forms the central atom of chlorophyll.[29] 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.[32] Magnesium also acts as an activator for many critical enzymes, including ribulosbiphosphate 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.[29] After prolonged magnesium deficiency, necrosis and dropping of older leaves occurs. Plants deficient in magnesium also produce smaller, woodier fruits.

Magnesium deficiency 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. For a more organic solution, applying home-made compost mulch can prevent leaching during excessive rainfall and provide plants with sufficient amounts of nutrients, including magnesium.[33]

See also

References

  1. ↑ "Definition of Magnesium Deficiency". MedicineNet.com. Retrieved 31 May 2014.
  2. 1 2 3 4 5 6 7 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.
  3. 1 2 Goldman, Lee; Schafer, Andrew I. (2015). Goldman-Cecil Medicine E-Book. Elsevier Health Sciences. p. 775. ISBN 9780323322850.
  4. 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: 1–13. doi:10.1007/s00467-016-3416-3. ISSN 0931-041X.
  5. ↑ Kobrin, SM; Goldfarb, S (Nov 1990). "Magnesium deficiency". Seminars in nephrology. 10 (6): 525–35. PMID 2255809.
  6. ↑ 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: hcw048. doi:10.1093/qjmed/hcw048. PMID 27016536.
  7. ↑ http://jasn.asnjournals.org/content/10/7/1616.full
  8. ↑ ZALMAN S. AGUS (1999). "Hypomagnesemia". Journal of the American Society of Nephrology. 10 (7): 1616.
  9. 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.
  10. ↑ http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm245275.htm
  11. ↑ 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.
  12. 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.
  13. ↑ 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.
  14. ↑ Sihler, KC; Napolitano, LM (January 2010). "Complications of massive transfusion". Chest. 137 (1): 209–20. doi:10.1378/chest.09-0252. PMID 20051407.
  15. 1 2 3 4 "Magnesium: Fact Sheet for Health Professionals". nih.gov. National Institutes of Health. Retrieved 8 November 2014.
  16. ↑ 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.
  17. ↑ Agus, Zalman (July 1999). "Hypomagnesemia". Journal of the American Society of Nephrology. 10 (7): 1616–1622. PMID 10405219.
  18. ↑ 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.
  19. 1 2 Swaminathan, R. "Magnesium Metabolism and its Disorders". Clin Biochem Rev. 24: 47–66. PMC 1855626. PMID 18568054.
  20. ↑ Famularo G1, Gasbarrone L, Minisola G. Hypomagnesemia and proton-pump inhibitors. Expert Opin Drug Saf. 2013 Sep;12(5):709-16.
  21. ↑ Durlach J, Durlach V, Bac P, Bara M, Guiet-Bara A (1994). "Magnesium and therapeutics". Magnes Res. 7 (3–4): 313–28. PMID 7786695.
  22. ↑ Firoz M, Graber M (2001). "Bioavailability of US commercial magnesium preparations". Magnes Res. 14 (4): 257–62. PMID 11794633.
  23. ↑ 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.
  24. ↑ 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.
  25. ↑ "Nutrient Intakes Percent of population 2 years old and over with adequate intakes based on average requirement". Community Nutrition Mapping Project. 2009-07-29. Retrieved 2012-02-11.
  26. ↑ "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. Retrieved 8 November 2014.
  27. ↑ 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: 1138. doi:10.1001/jama.1934.02750140024010.
  28. ↑ "Definition of Hypomagnesemia". MedicineNet.com. Retrieved 31 May 2014.
  29. 1 2 3 Norman P.A. Huner; William Hopkins. "3 & 4". Introduction to Plant Physiology 4th Edition. John Wiley & Sons, Inc. ISBN 978-0-470-24766-2.
  30. ↑ Ding Y.; Chang C.; Luo W. "High Potassium Aggravates the Oxidative Stress Induced by Magnesium Deficiency in Rice Leaves". Pedosphere. 18 (3). pp. 316–327.
  31. ↑ Merhaut, D.J. (2006). "Magnesium". In Barker A.V.; Pilbeam D.J. Handbook of plant nutrition. Boca Raton: CRC Press. p. 154. ISBN 9780824759049.
  32. ↑ Hermans C.; Vuylsteke F.; Coppens F. "Systems Analysis of the responses to long-term magnesium deficiency and restoration in Arabidopsis thaliana". New Phytologist. 187. pp. 132–144.
  33. ↑ "Problem Solving: Magnesium Deficiency".
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