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==Causes==
==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.<ref>http://jasn.asnjournals.org/content/10/7/1616.full</ref><ref name="icu">{{cite journal |author=ZALMAN S. AGUS |title=Hypomagnesemia |journal=Journal of the American Society of Nephrology |volume=10 |issue=7 |page=1616 |year=1999}}</ref> Hypomagnesemia is probably underdiagnosed, as testing for serum magnesium levels is not routine.
{{See also|Hypomagnesemia#Causes}}

Causes of magnesium deficiency include diet, alcohol abuse, chronic stress, poorly controlled diabetes, excessive or chronic vomiting and/or diarrhea. Phytate<ref name="pmid6747725">{{cite journal|last=Forbes|first=RM |author2=Parker, HM |author3=Erdman JW, Jr|title=Effects of dietary phytate, calcium and magnesium levels on zinc bioavailability to rats.|journal=The Journal of Nutrition|date=Aug 1984|volume=114|issue=8|pages=1421–5|pmid=6747725|url=http://jn.nutrition.org/content/114/8/1421.full.pdf}}</ref> or [[oxalate]]<ref name="Great Plains Labs - oxalates">[http://www.greatplainslaboratory.com/home/eng/oxalates.asp Oxalates may absorb magnesium], background information indicating possibility of oxalates absorbing magnesium.</ref> in the diet may bind magnesium, causing it to be eliminated from rather than absorbed in the colon. Certain drugs can deplete magnesium levels such as [[osmotic diuretic]]s, [[cisplatin]], [[ciclosporin]], [[amphetamine]]s, and possibly [[proton pump inhibitor]]s.<ref name=fda>{{cite web|title=FDA Drug Safety Communication: Low magnesium levels can be associated with long-term use of Proton Pump Inhibitor drugs (PPIs)|url=http://www.fda.gov/drugs/drugsafety/ucm245011.htm|website=fda.gov|publisher=F.D.A. U.S. Food and Drug Administration|accessdate=8 November 2014}}</ref> Also deficiency may occur in [[Bartter syndrome]]<ref name=bartter>{{cite journal|last1=Rodríguez-Soriano|first1=Juan|title=Bartter and related syndromes: the puzzle is almost solved|journal=Pediatric Nephrology|date=May 1998|volume=12|issue=4|pages=315–327|doi=10.1007/s004670050461|url=https://link.springer.com/article/10.1007%2Fs004670050461|accessdate=8 November 2014|pmid=9655365}}</ref> and [[Gitelman syndrome]].<ref name=gitelman>{{cite journal|last1=Simon|first1=DB|last2=Nelson-Williams|first2=C|title=Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter|journal=Nat Genet|date=January 1996|volume=12|issue=1|pages=24–30|pmid=8528245|url=https://www.ncbi.nlm.nih.gov/pubmed?term=david%20b%20simon%20gitelman%27s%20variant|accessdate=8 November 2014|doi=10.1038/ng0196-24|display-authors=etal}}</ref>
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===
* Alcoholism. Hypomagnesemia occurs in 30% of [[alcohol abuse]]rs and in 85% of [[delirium tremens]] inpatients, due to [[malnutrition]] and chronic [[diarrhea]]. {{citation needed|date=June 2013}} Alcohol stimulates the kidneys' excretion of magnesium, which is also increased because of [[Alcoholic ketoacidosis|alcoholic]] and [[diabetic ketoacidosis]], [[hypophosphatemia|low blood phosphate levels]], and [[hyperaldosteronism]] resulting from liver disease. Also, hypomagnesemia is related to [[thiamine]] deficiency because magnesium is needed for transforming thiamine into [[thiamine pyrophosphate]].

===Medications===
* Loop and thiazide diuretic use (the most common cause of hypomagnesemia)<ref name="homeo">{{cite journal |vauthors=Whang R, Hampton EM, Whang DD |title=Magnesium homeostasis and clinical disorders of magnesium deficiency |journal=Ann Pharmacother |volume=28 |issue=2 |pages=220–6 |year=1994 |pmid=8173141 |doi= 10.1177/106002809402800213 }}</ref>
* Antibiotics (i.e. [[aminoglycoside]], [[amphotericin]], [[pentamidine]], [[gentamicin]], [[tobramycin]], [[viomycin]]) block resorption in the [[loop of Henle]]. 30% of patients using these antibiotics have hypomagnesemia. {{citation needed|date=June 2013}}
* Long term use of [[proton-pump inhibitor]]s such as [[omeprazole]].<ref>http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm245275.htm</ref><ref>{{cite journal|last=Sheen|first=E|author2=Triadafilopoulos, G|title=Adverse effects of long-term proton pump inhibitor therapy.|journal=Digestive Diseases and Sciences|date=April 2011|volume=56|issue=4|pages=931–50|pmid=21365243|doi=10.1007/s10620-010-1560-3}}</ref>
* Other drugs.
** [[Digitalis]], displaces magnesium into the cell. Digitalis causes an increased intracellular concentration of sodium, which in turn increases intracellular calcium by passively decreasing the action of the sodium-calcium exchanger in the sarcolemma. The increased intracellular calcium gives a positive inotropic effect.<ref name="homeo" />
** [[Adrenergics]], displace magnesium into the cell
** [[Cisplatin]], stimulates kidney excretion
** [[Ciclosporin]], stimulates kidney excretion
** [[Mycophenolate mofetil]]

=== Genetic causes ===
* Gitelman-like diseases, which include the syndromes caused by [[genetic mutations]] in ''[[Sodium-chloride symporter|SLC12A3]]'', ''[[CLCNKB|CLNCKB]]'',<ref name="cameron" /> ''[[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.<ref name=":0" />
* [[Hypercalciuria|Hypercalciuric]] hypomagnesemic syndromes, which encompass the syndromes caused by mutations in ''[[CLDN16]]'', ''[[CLDN19]]'', ''[[Calcium-sensing receptor|CASR]]'' or ''[[CLCNKB]]''. In these diseases, reabsorption of [[Cations, divalent|divalent cations]] (such as magnesium and calcium) in the [[Thick ascending limb of loop of Henle|thick ascending limb of Henle's loop]] of the kidney is impaired. This results in loss of magnesium and calcium in the urine.<ref name=":0" />
* [[Mitochondrial disease|Mitochondriopathies]], such as caused by mutations in ''[[SARS2]]'', ''[[MT-TI]]'' or as seen with [[Kearns–Sayre syndrome|Kearns-Sayre syndrome]].<ref name=":0" />
* Other genetic causes of hypomagnesemia, such as mutations in ''[[TRPM6]]'', ''[[CNNM2]]'', ''[[EGF (gene)|EGF]]'', ''[[EGFR (gene)|EGFR]]'', ''[[Kv1.1|KCNA1]]'' or ''[[FAM111A]]''. Many of the proteins encoded by these genes play a role in the [[Transcellular transport|transcellular]] absorption of magnesium in the distal convoluted tubule.<ref name=":0" />

===Metabolic abnormalities===
* Insufficient [[selenium]],<ref>{{cite journal |vauthors=Chareonpong-Kawamoto N, Yasumoto K |title=Selenium deficiency as a cause of overload of iron and unbalanced distribution of other minerals |journal=Biosci. Biotechnol. Biochem. |volume=59 |issue=2 |pages=302–6 |year=1995 |pmid=7766029 |doi= 10.1271/bbb.59.302|url=}}</ref> vitamin D, sunlight exposure or [[vitamin B6]].{{citation needed|date=June 2013}}
* 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 [[coeliac disease|celiac sprue]] can all cause hypomagnesemia.
* Postobstructive diuresis, diuretic phase of acute tubular necrosis (ATN) and [[kidney transplant]].{{citation needed|date=June 2013}}

===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.<ref>{{cite journal|last=Sihler|first=KC|author2=Napolitano, LM|title=Complications of massive transfusion.|journal=Chest|date=January 2010|volume=137|issue=1|pages=209–20|pmid=20051407|doi=10.1378/chest.09-0252}}</ref>


==Pathophysiology==
==Pathophysiology==

Revision as of 01:30, 11 October 2018

This article is about magnesium deficiency. For low blood magnesium, see Hypomagnesemia.
Magnesium deficiency
Other namesHypomagnesia, hypomagnesemia
Magnesium
SpecialtyEndocrinology

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]

Causes include inadequate intake or impaired absorption of magnesium. The diagnosis is typically based on finding low blood magnesium levels (hypomagnesemia).[2]

Treatment is generally by increasing of magnesium in diet or supplements either by mouth or intravenously.

Signs and symptoms

Symptoms of magnesium deficiency include hyperexcitability, muscular symptoms (cramps, tremor, fasciculations, spasms, tetany, weakness), fatigue, loss of appetite, apathy, confusion, sound and light sensitivity, anxiety, insomnia, irritability, poor memory, and reduced ability to learn. Moderate to severe magnesium deficiency can cause tingling or numbness, heart changes, rapid heartbeat, continued muscle contractions, nausea, vomiting, migraines, personality changes, delirium, hallucinations, low calcium levels, low serum potassium levels, retention of sodium, low circulating levels of parathyroid hormone (PTH),[3] and potentially death from heart failure.[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][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.[15]

Pathophysiology

See also: Hypomagnesemia § Pathophysiology

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

Diagnosis

Magnesium deficiency is not easy to directly measure.[17] Typically it is based on finding low blood magnesium levels (hypomagnesemia).[2]

Treatments

Magnesium deficiency can often be effectively treated with an oral magnesium preparation. It can also be treated by using a nebulizer filled with magnesium sulphate or magnesium chloride dissolved in water. Nebulising has the advantage of taking effect within minutes, relieving muscle pain, tension or breathing difficulties. Nebulizers can be bought without prescription in the U.K, as can magnesium sulphate and magnesium chloride. For those that require frequent doses, a portable, battery driven nebulizer is useful although more expensive and prone to break down than older style plug in nebulizers.

Severe hypomagnesemia is often treated medically with intravenous or intramuscular magnesium sulfate solution, which is completely bioavailable, and effective.

Food

Food sources of magnesium include leafy green vegetables, soybeans, nuts, and fruits and egg [16]

Epidemiology

57% of the US population does not meet the US RDA for dietary intake of magnesium.[18] 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[19] or chronic alcoholism.[16]

History

Magnesium deficiency in humans was first described in the medical literature in 1934.[20]

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.[21] Magnesium deficiency can be present without hypomagnesemia, and hypomagnesemia can be present without magnesium deficiency.[17] 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.[22] Excess potassium, generally due to fertilizers, further aggravates the stress from magnesium deficiency,[23] as does aluminium toxicity.[24]

Magnesium has an important role in photosynthesis because it forms the central atom of chlorophyll.[22] 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.[25] 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.[22] 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.[26]

See also

References

  1. ^ "Definition of Magnesium Deficiency". MedicineNet.com. Retrieved 31 May 2014.
  2. ^ a b Goldman, Lee; Schafer, Andrew I. (2015). Goldman-Cecil Medicine E-Book. Elsevier Health Sciences. p. 775. ISBN 9780323322850.
  3. ^ Rude RK, Shils ME. Magnesium. In: Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ, eds. Modern Nutrition in Health and Disease. 10th ed. Baltimore: Lippincott Williams & Wilkins; 2006:223-247
  4. ^ Blaylock, Russell L. (2006). Health and nutrition secrets that can save your life. Albuquerque, NM: Health Press. p. 395. ISBN 978-0-929173-48-1.
  5. ^ Kobrin, SM; Goldfarb, S (Nov 1990). "Magnesium deficiency". Seminars in nephrology. 10 (6): 525–35. PMID 2255809.
  6. ^ MedlinePlus Encyclopedia: Magnesium in diet
  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. ^ a b 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. ^ Cite error: The named reference cameron was invoked but never defined (see the help page).
  13. ^ a b c d Cite error: The named reference :0 was invoked but never defined (see the help page).
  14. ^ 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.
  15. ^ Sihler, KC; Napolitano, LM (January 2010). "Complications of massive transfusion". Chest. 137 (1): 209–20. doi:10.1378/chest.09-0252. PMID 20051407.
  16. ^ a b c d "Magnesium: Fact Sheet for Health Professionals". nih.gov. National Institutes of Health. Retrieved 8 November 2014.
  17. ^ a b Swaminathan, R. "Magnesium Metabolism and its Disorders". Clin Biochem Rev. 24: 47–66. PMC 1855626. PMID 18568054.
  18. ^ "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.
  19. ^ Cite error: The named reference fda was invoked but never defined (see the help page).
  20. ^ 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.
  21. ^ "Definition of Hypomagnesemia". MedicineNet.com. Retrieved 31 May 2014.
  22. ^ a b c Norman P.A. Huner; William Hopkins. "3 & 4". Introduction to Plant Physiology 4th Edition. John Wiley & Sons, Inc. ISBN 978-0-470-24766-2.
  23. ^ 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.
  24. ^ 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)
  25. ^ 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.
  26. ^ "Problem Solving: Magnesium Deficiency".

External links

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