ULOGA MAGNEZIJUMA I ZNAČAJ HIPOMAGNEZIJEMIJE U LJUDSKOM ORGANIZMU
Sažetak
Magnezijum je drugi najzastupljeniji katjon u ćeliji. Najveći procenat magnezijuma je u kostima (preko 60%), nešto manje ima ga u mišićima i mekim tkivima. U cirkulaciji je oko 1% magnezijuma, podeljenog u tri oblika, od kojih jonizovani ima najveću biološku aktivnost. Magnezijum je uključen u gotovo svaki metabolički i biohemijski proces unutar ćelije. Homeostaza magnezijuma je neophodna za optimalno funkcionisanje organizma.
Analiza krvi predstavlja najjednostavniji metod procene statusa magnezijuma. Za merenje magnezijuma u krvi mogu se koristiti: puna krv i njene frakcije (serum i plazma), kao i ćelije krvi (eritrociti, mononuklearne ćelije periferne krvi i trombociti). Merenje jonizovanog magnezijuma je jedna od najnovijih i najpreciznijih metoda pošto procenjuje status biološki najaktivnije forme magnezijuma. Kako se merenje vrši iz uzorka periferne krvi, ovaj metod je relativno brz i jednostavan što omogućava brzu identifikaciju osoba sa nedostatkom ovog važnog jona i rizikom koji taj nedostatak nosi.
Nedostatak magnezijuma može biti uslovljen lošom ishranom, hormonskom neravnotežom, elektrolitnim disbalansom i brojnim drugim faktorima. U situacijama postepenog nastanka hipomagnezijemije, čak i težak deficit može proći bez vidljivih znakova. U većini slučajeva nedostatak magnezijuma počinje sa tegobama u vidu mučnine i osećajem umora. Nedostatak magnezijuma povezuje se sa kardiovaskularnim oboljenjima, metaboličkim sindromom i dijabetesom, fibromialgijom i gotovo svim bolestima CNS-a. Na osnovu do sada utvrđenih povezanosti određenih bolesti sa nedostatakom magnezijuma, brza procena statusa ovog značajnog dvovalentnog katjona u organizmu bi omogućila bolji skrining, precizniju dijagnostiku i brži oporavak.
Reference
1. Bodaker I, Sharon I, Suzuki MT, et al. Comparative community genomics in the Dead Sea: an increasingly extreme environment. ISME J. 2010; 4:399–407.
2. de Baaij JH, Hoenderop JG, Bindels RJ. Magnesium in man: implications for health and disease. Physiol Rev. 2015; 95(1):1-46.
3. Jahnen-Dechent W, Ketteler M. Magnesium basics. Clin Kidney J. 2012; 5 (Suppl 1): i3-i14.
4. Romani A. Regulation of magnesium homeostasis and transport in mammalian cells. Arch Biochem Biophys. 2007; 458(1):90-102.
5. https: /www.ncbi.nlm.nih.gov/books/NBK545442/table/appJ_tab3/?report=objectonly
6. Saris NE, Mervaala E, Karppanen H, Khawaja JA, Lewenstam A. Magnesium. An update on physiological, clinical and analytical aspects. Clin Chim Acta. 2000; 294(1-2):1-26.
7. Jeroen H., de Baaij F., Joost G., Hoenderop J., Rene J., Bindels M. Regulation of magnesium balance: Lessons learned from human genetic disease. Clin. Kidney J. 2012; 5: i15–i24.
8. Anast C.S. Magnesium studies in relation to vitamin D-resistant rickets. Pediatrics. 1967; 40: 425–435.
9. Zofková I., Kancheva R.L. The relationship between magnesium and calciotrophic hormones. Magnes. Res. 1995; 8: 77–84.
10. Groenestege WM, Hoenderop JG, van den Heuvel L, Knoers N, Bindels RJ. The epithelial Mg2+ channel transient receptor potential melastatin 6 is regulated by dietary Mg2+ content and estrogens. J Am Soc Nephrol. 2006; 17(4):1035-43.
11. Amano T, Matsubara T, Watanabe J, Nakayama S, Hotta N. Insulin modulation of intracellular free magnesium in heart: involvement of protein kinase C. Brit J Pharmacol. 2000; 130:731–8.
12. Caspi R., Altman T., Dreher K., Fulcher C.A., Subhraveti P., Keseler I.M., Kothari A., Krummenacker M., Latendresse M., Mueller L.A., et al. The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of pathway/genome databases. Nucleic Acids Res. 2012; 40: D742–D753.
13. Fiorentini D, Cappadone C, Farruggia G, Prata C. Magnesium: Biochemistry, Nutrition, Detection, and Social Impact of Diseases Linked to Its Deficiency. Nutrients. 2021; 13(4):1136.
14. Swaminathan R. Magnesium metabolism and its disorders. Clin Biochem Rev. 2003; 24(2):47-66.
15. Anastassopoulou J., Theophanides T. Magnesium-DNA interactions and the possible relation of magnesium to carcinogenesis. Irradiation and free radicals. Crit. Rev. Oncol. 2002; 42:79–91.
16. Zhu X., Shrubsole M., Ness R.M., Hibler E., Cai Q., Long J., Chen Z., Li G., Jiang M., Hou L., et al. Calcium/magnesium intake ratio, but not magnesium intake, interacts with genetic polymorphism in relation to colorectal neoplasia in a two-phase study. Mol. Carcinog. 2016; 55:1449–1457. doi: 10.1002/mc.22387
17. Fandilolu P.M., Kamble A.S., Dound A.S., Sonawane K.D. Role of Wybutosine and Mg2+ Ions in Modulating the Structure and Function of tRNAPhe: A Molecular Dynamics Study. ACS Omega. 2019; 4:21327–21339.
18. Castiglioni S., Maier J.A. Magnesium and cancer: A dangerous liason. Magnes. Res. 2011; 24:92–100).
19. Lu WC, Pringa E, Chou L. Effect of magnesium on the osteogenesis of normal human osteoblasts. Magnes Res. 2017; 30(2):42-52.
20. Gröber U, Schmidt J, Kisters K. Magnesium in Prevention and Therapy. Nutrients. 2015; 7(9):8199-226.
21. Rodríguez-Ortiz M.E., Canalejo A., Herencia C., Martínez-Moreno J.M., Peralta-Ramírez A., Perez-Martinez P., Navarro-González J.F., Rodríguez M., Peter M., Gundlach K., et al. Magnesium modulates parathyroid hormone secretion and upregulates parathyroid receptor expression at moderately low calcium concentration. Nephrol. Dial. Transplant. 2014; 29:282–289.
22. Nielsen FH. Magnesium deficiency and increased inflammation: current perspectives. J Inflamm Res. 2018; 11:25-34.
23. White R.E., Hartzell H.C. Effects of intracellular free magnesium on calcium current in isolated cardiac myocytes. Science. 1988; 239:778–780
24. Buri A, McGuigan JA. Intracellular free magnesium and its regulation, studied in isolated ferret ventricular muscle with ion-selective microelectrodes. Exp Physiol. 1990; 75(6):751-61.
25. Seyama T, Kamei Y, Iriyama T, Imada S, Ichinose M, Toshimitsu M, Fujii T, Asou H. Pretreatment with magnesium sulfate attenuates white matter damage by preventing cell death of developing oligodendrocytes. J Obstet Gynaecol Res. 2018; 44(4):601-607.
26. Stangherlin A, O'Neill JS. Signal Transduction: Magnesium Manifests as a Second Messenger. Curr Spasov AA, Iezhitsa IN, Kravchenko MS, Kharitonova MV. Features of central neurotransmission in animals in conditions of dietary magnesium deficiency and after its correction. Neurosci Behav Physiol. 2009 Sep;39(7):645-53. Biol. 2018; 28(24):R1403-R1405.
27. Erecinska M, Silver IA: Metabolism and role of glutamate in mammalian brain. Prog Neurobiol 1990; 35:245-296
28. Derom ML, Martinez-Gonzalez MA, Sayon-Orea Mdel C, Bes-Rastrollo M, Beunza JJ, Sanchez-Villegas A. Magnesium intake is not related to depression risk in Spanish university graduates. J Nutrition. 2012; 142(6):1053–9.
29. Orrenius S, Zhivotovsky B, Nicotera P. Regulation of cell death: the calcium-apoptosis link. Nat Rev Mol Cell Biol. 2003; 4:552–565.
30. Reynolds JL, Joannides AJ, Skepper JN, McNair R, Schurgers LJ, Proudfoot D, Jahnen-Dechent W, Weissberg PL, Shanahan CM. Human vascular smooth muscle cells undergo vesicle-mediated calcification in response to changes in extracellular calcium and phosphate concentrations: a potential mechanism for accelerated vascular calcification in ESRD. J Am Soc Nephrol. 2004; 15(11):2857-67.
31. Poleszak E., Vlaz P., Vrobel A., Fidecka S., Novak G. NMDA/glutamate mechanism of magnesium-induced anxiolytic behavior in mice. Pharmacol. Tail. 2008; 60 :655–663
32. Zhu I., Auerbach A. Occupancy of Na + and Mg 2+ block the N-methyl-d-aspartate receptor channel. J. Gen. Physiol. 2001; 117:275–286.
33. Schvartz RD, Wagner JP, Yu Ks, Martin D. Bidirectional Modulation of GABA-Gated Chloride Channel by Divalent Cation: Inhibition by Ca 2+ and Enhancement by Mg 2+ J. Neurochem. 1994; 62: 916–922.
34. Barragán-Rodríguez L, Rodríguez-Morán M, Guerrero-Romero F: Efficacy and safety of oral magnesium supplementation in the treatment of depression in the elderly with type 2 diabetes: a randomized, equivalent trial. Magnes Res 2008; 21:218-223.
35. Kirkland A., Sarlo G., Holton K. The Role of Magnesium in Neurological Disorders. Nutrients. 2018; 10:730.
36. Witkowski M, Hubert J, Mazur A. Methods of assessment of magnesium status in humans: a systematic review. Magnes Res. 2011; 24(4):163-80
37. Workinger JL, Doyle RP, Bortz J. Challenges in the Diagnosis of Magnesium Status. Nutrients. 2018; 10(9):1202.
38. Gröber U, Schmidt J, Kisters K. Magnesium in Prevention and Therapy. Nutrients. 2015; 7(9):8199-226.
39. Touyz R. Magnesium in clinical medicine. Front Biosci 2004; 9:1278-93.
40. Elin RJ. Assessment of magnesium status for diagnosis and therapy. Magnes Res. 2010; 23(4):S194-8.
41. Ismail, Y.; Ismail, A.A. The underestimated problem of using serum magnesium measurements to exclude magnesium deficiency in adults; a health warning is needed for “normal” results. Clin. Chem. Lab. Med. 2010, 48, 323–327.
42. Von Ehrlich, E.; Barbagallo, M.; Classen, H.G.; Guerrero-Romero, F.; Morren, F.C.; Rodriguez-Moran, M.; Vierling, W.; Vormann, J; Kisters, K. The significance of magnesium in insulin resistance, metabolic syndrome, and diabetes—Recommendations of the Association of Magnesium Research e.V. Diabetol. Stoffwechs. 2014, 9, 96–100
43. Vormann, J. Update: Magnesium und Diabetes. OM—Z. Orthomol. Med. 2014, 1, 6–8.
44. Razzaque MS. Magnesium: Are We Consuming Enough? Nutrients. 2018; 10(12):1863.
45. Fawcett W.J., Haxby E.J., Male D.A. Magnesium: Physiology and Pharmacology. Br. J. Anaesth. 1999; 83:302–320.
46. Speich M, Bousquet B, Nicolas G. Reference values for ionized, complexed, and protein-bound plasma magnesium in men and women. Clin Chem. 1981; 27:246–248.
47. WALSER M. Ion association. VI. Interactions between calcium, magnesium, inorganic phosphate, citrate and protein in normal human plasma. J Clin Invest. 1961; 40(4):723-30.
48. Rosanoff A., Wolf F.I. A guided tour of presentations at the xiv international magnesium symposium. Magnes. Res. 2016; 29:55–59
49. Meyerspeer M, Boesch C, Cameron D, Dezortová M, Forbes SC, Heerschap A, Jeneson JAL, Kan HE, Kent J, Layec G, Prompers JJ, Reyngoudt H, Sleigh A, Valkovič L, Kemp GJ; Experts' Working Group on 31P MR Spectroscopy of Skeletal Muscle. 31 P magnetic resonance spectroscopy in skeletal muscle: Experts' consensus recommendations. NMR Biomed. 2020; 34(5):e4246.
50. Reyngoudt, H., Lopez Kolkovsky, A. L., & Carlier, P. G. (2019). Free intramuscular Mg2+ concentration calculated using both 31P and 1H NMRS‐based pH in the skeletal muscle of Duchenne muscular dystrophy patients. NMR in Biomedicine, 32(9), e4115.
51. Schutten JC, Gomes-Neto AW, Navis G, Gansevoort RT, Dullaart RPF, Kootstra-Ros JE, Danel RM, Goorman F, Gans ROB, de Borst MH, Jeyarajah EJ, Shalaurova I, Otvos JD, Connelly MA, Bakker SJL. Lower Plasma Magnesium, Measured by Nuclear Magnetic Resonance Spectroscopy, is Associated with Increased Risk of Developing Type 2 Diabetes Mellitus in Women: Results from a Dutch Prospective Cohort Study. J Clin Med. 2019; 8(2):169.
52. Scarpati G., Baldassarre D., Oliva F., Pascale G., Piazza O. Ionized or Total Magnesium Levels, What Should We Measure in Critical Ill Patients? Transl. Med. UniSa. 2020; 23: 68–76.
53. Zittermann A. Magnesium deficit ? overlooked cause of low vitamin D status? BMC Med. 2013; 11:229.
54. Deng X, Song Y, Manson JE, Signorello LB, Zhang SM, Shrubsole MJ, Ness RM, Seidner DL, Dai Q. Magnesium, vitamin D status and mortality: results from US National Health and Nutrition Examination Survey (NHANES) 2001 to 2006 and NHANES III. BMC Med. 2013; 11:187.
55. Palmer BF, Clegg DJ. Electrolyte and Acid-Base Disturbances in Patients with Diabetes Mellitus. N Engl J Med. 2015 Aug 6; 373(6):548-59.
56. Sarrafzadegan N, Khosravi-Boroujeni H, Lotfizadeh M, Pourmogaddas A, Salehi-Abargouei A. Magnesium status and the metabolic syndrome: A systematic review and meta-analysis. Nutrition. 2016; 32(4):409-17.
57. Riley J.M., Kim H., Averch T.D., Kim H.J. Effect of magnesium on calcium and oxalate ion binding. J. Endourol. 2013; 27:1487–1492.
58. Benassi L., Barletta F.P., Baroncini L., Bertani D., Filippini F., Beski L., Nani A., Tesauri P., Tridenti G. Effectiveness of magnesium pidolate in the prophylactic treatment of primary dysmenorrhea. Clin. Exp. Obstet. Gynecol. 1992; 19:176–179.
59. Ebrahimi E., Khayati Motlagh S., Nemati S., Tavakoli Z. Effects of magnesium and vitamin B6 on the severity of premenstrual syndrome symptoms. J. Caring Sci. 2012; 1: 183–189.,
60. Alraek T., Lee M.S., Choi T.Y., Cao H., Liu J. Complementary and alternative medicine for patients with chronic fatigue syndrome: A systematic review. BMC Complement. Altern. Med. 2011.
61. Bagis S., Karabiber M., As I., Tamer L., Erdogan C., Atalay A. Is magnesium citrate treatment effective on pain, clinical parameters and functional status in patients with fibromyalgia? Rheumatol. Int. 2013; 33:167–172
62. Choi Y.H., Miller J.M., Tucker K.L., Hu H., Park S.K. Antioxidant vitamins and magnesium and the risk of hearing loss in the US general population. Am. J. Clin. Nutr. 2014; 99:148–155.
63. Cevette M.J., Barrs D.M., Patel A., Conroy K.P., Sydlowski S., Noble B.N., Nelson G.A., Stepanek J. Phase 2 study examining magnesium-dependent tinnitus. Int. Tinnitus J. 2011; 16:168–173.148
64. Astiglioni S., Cazzaniga A., Albisetti W., Maier J.A. Magnesium and osteoporosis: Current state of knowledge and future research directions. Nutrients. 2013; 5:3022–3033.
65. Domitrz I, Cegielska J. Magnesium as an Important Factor in the Pathogenesis and Treatment of Migraine-From Theory to Practice. Nutrients. 2022; 14 (5):1089.
66. Altman D., Carroli G., Duley L., Farrell B., Moodley J., Neilson J., Smith D. Magpie Trial Collaboration Group. Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: A randomised placebo-controlled trial. Lancet. 2002;359:1877–1890
67. Vierling, W.; Liebscher, D.H.; Micke, O.; von Ehrlich, B.; Kisters, K. Magnesium deficiency and therapy in cardiac arrhythmias: Recommendations of the German Society for Magnesium Research. Dtsch. Med. Wochenschr. 2013; 138: 1165–1171.
68. Spätling L, Classen HG, Külpmann WR, et al. [Diagnosing magnesium deficiency. Current recommendations of the Society for Magnesium Research]. Fortschritte der Medizin. Originalien. 2000; 118 Suppl 2: 49-53. PMID: 15700486.
69. Dhillon VS, Deo P, Thomas P, Fenech M. Low Magnesium in Conjunction with High Homocysteine and Less Sleep Accelerates Telomere Attrition in Healthy Elderly Australian. Int J Mol Sci. 2023; 24(2): 982.
70. Mousain-Bosc M., Roche M., Polge A., Pradal-Prat D., Rapin J., Bali J.P. Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6. I. Attention deficit hyperactivity disorders. Magnes. Res. 2006; 19: 46–52
71. Barbagallo M., Belvedere M., Di Bella G., Dominguez L.J. Altered ionized magnesium levels in mild-to-moderate Alzheimer’s disease. Magnes. Res. 2011; 24:S115–S121
72. Bardgett M.E., Schultheis P.J., McGill D.L., Richmond R.E., Wagge J.R. Magnesium deficiency impairs fear conditioning in mice. Brain Res. 2005; 1038:100–106.
73. Li W., Yu J., Liu Y., Huang X., Abumaria N., Zhu Y., Huang X., Xiong W., Ren C., Liu X.G., et al. Elevation of brain magnesium prevents and reverses cognitive deficits and synaptic loss in Alzheimer’s disease mouse model. J. Neurosci. 2013; 33: 8423–8441.
74. Cuciureanu MD, Vink R. Magnesium and stress. In: Vink R, Nechifor M, editors. Magnesium in the Central Nervous System [Internet]. Adelaide (AU): University of Adelaide Press; 2011. PMID: 29920004.
75. Serita T, Miyahara M, Tanimizu T, Takahashi S, Oishi S, Nagayoshi T, Tsuji R, Inoue H, Uehara M, Kida S. Dietary magnesium deficiency impairs hippocampus-dependent memories without changes in the spine density and morphology of hippocampal neurons in mice. Brain Res Bull. 2019; 144: 149-157.
76. Camardese G, Risio LD, Pizi G, Mattioli B, Buccelletti F, Serrani R, et al. Plasma magnesium levels and treatment outcome in depressed patients. Nutr Neurosci. 2012; 15(2): 78–84.
77. Baj J, Forma A, Sitarz E, Karakuła K, Flieger W, Sitarz M, Grochowski C, Maciejewski R, Karakula-Juchnowicz H. Beyond the Mind-Serum Trace Element Levels in Schizophrenic Patients: A Systematic Review. Int J Mol Sci. 2020;21(24):9566.
78. Slutsky I., Sadeghpour S., Li B., Liu G. Enhancement of synaptic plasticity through chronically reduced Ca2+ flux during uncorrelated activity, Neuron, 44 .2004, pp. 835-849
79. Shahrami A., Assarzadegan F., Hatamabadi H.R., Asgarzadeh M., Sarehbandi B., Asgarzadeh S. Comparison of therapeutic effects of magnesium sulfate vs. dexamethasone/metoclopramide on alleviating acute migraine headache. J. Emerg. Med. 2015; 48:69–76.