Magnesium: The Forgotten Electrolyte—A Review on Hypomagnesemia
Open accessAbstract
Magnesium is the fourth most abundant cation in the body and the second most abundant intracellular cation. It plays an important role in different organ systems at the cellular and enzymatic levels. Despite its importance, it still has not received the needed attention either in the medical literature or in clinical practice in comparison to other electrolytes like sodium, potassium, and calcium. Hypomagnesemia can lead to many clinical manifestations with some being life-threatening. The reported incidence is less likely than expected in the general population. We present a comprehensive review of different aspects of magnesium physiology and hypomagnesemia which can help clinicians in understanding, identifying, and treating this disorder.
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Magnesium deficiency may contribute to hypokalemia by enhancing renal potassium loss via disinhibition of the renal outer medullary potassium channel (ROMK) in the distal nephron.
“Magnesium deficiency may contribute to hypokalemia by enhancing renal potassium loss via disinhibition of renal outer medullary potassium channel (ROMK) in the distal nephron [41].”
From Thyrotoxic Hypokalemic Periodic Paralysis: Pathophysiological Mechanisms (2025) · cites this paper as [41]
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“This interaction highlights the crucial role of magnesium in the broader context of electrolyte homeostasis [10].”
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Francini, F., Gobbi, L., Ravarotto, V., Toniazzo, S. R. F., Nalesso, F., Spinella, P., & Calò, L. A. (2021) · Nutrients · doi:10.3390/nu13092960 · Cited by 14 · see citing works
“Magnesium supplements should be taken in small frequent doses (3–4 times/day) and with meals in order to reduce/avoid the chance of diarrhea that may worsen hypokalemia and volume depletion [24].”
BackgroundThe Laboratory and Clinical Perspectives of Magnesium Imbalance
Rahim, S. N. A., Nordin, N., Omar, W. F. A. W., Zulkarnain, S., Kumar, S., Sinha, S., & Haque, M. (2023) · Cureus · doi:10.7759/cureus.49835 · Cited by 14 · see citing works
“The remaining 50% is in an ionized form fraction, representing the biologically active form [2].”
BackgroundAssociation between serum magnesium and anemia in patients with chronic kidney disease
Bıyık, Z., Yavuz, Y. C., & Altıntepe, L. (2020) · International Urology and Nephrology · doi:10.1007/s11255-020-02525-8 · Cited by 14 · see citing works
“Magnesium is known to be associated with several factors such as endothelial dysfunction, atherosclerosis, arrhythmias and insulin resistance [6].”
BackgroundGagliano, V., Schäffeler, F., Giorno, R. D., Bianchetti, M. G., Canarte, C. F. C., Regueira, J. J. C., & Gabutti, L. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11144015 · Cited by 13 · see citing works
“This was to be expected, since the prevalence of hypomagnesemia is estimated to be less than 2% in the general population [2,4], and our intent was explorative.”
BackgroundInfluentialCegielska, J., Szmidt-Sałkowska, E., Domitrz, W., Gaweł, M., Radziwoń-Zaleska, M., & Domitrz, I. (2021) · Nutrients · doi:10.3390/nu13082701 · Cited by 13 · see citing works
“The level of magnesium measured in blood serum does not reflect its content in the internal environment of platelets, erythrocytes, or neurons and myocytes [27].”
BackgroundComprehensive Review of Acute Pancreatitis Pain Syndrome
Beiriger, J., Khan, A. R., Yan, B. M., Ross, H. M., Wang, M., Carducci, M. P., Parra, N. S., Chowdhury, S., Erwin, R., Forrest, P., et al. (2023) · Gastrointestinal Disorders · doi:10.3390/gidisord5020014 · Cited by 12 · see citing works
Practical supplements for prevention and management of migraine attacks: a narrative review
Hajhashemy, Z., Golpour-Hamedani, S., Eshaghian, N., Sadeghi, O., Khorvash, F., & Askari, G. (2024) · Frontiers in Nutrition · doi:10.3389/fnut.2024.1433390 · Cited by 19 · see citing works
“Acute magnesium deficiency is usually asymptomatic, and if it is symptomatic, it is associated with symptoms, such as nausea, vomiting, lethargy, mood, and nervous disorders (depression, anxiety, and stress) (183, 184).”
Low extracellular magnesium induces phenotypic and metabolic alterations in C2C12-derived myotubes
Zocchi, M., Bartolini, M., Maier, J. A. M., & Castiglioni, S. (2023) · Scientific Reports · doi:10.1038/s41598-023-46543-9 · Cited by 11 · see citing works
An Update on Drug–Nutrient Interactions and Dental Decay in Older Adults
Bell, V., Rodrigues, A. R., Αντωνιάδου, Μ., Peponis, M., Varzakas, T. H., & Fernandes, T. H. (2023) · Nutrients · doi:10.3390/nu15234900 · Cited by 12 · see citing works
“This magnesium depletion may be associated with a decrease in active transport and changes in intestinal absorption, although its mechanism has not been fully clarified yet [107].”
BackgroundImbalance of Mg Homeostasis as a Potential Biomarker in Colon Cancer
Schiroli, D., Marraccini, C., Zanetti, E., Ragazzi, M., Gianoncelli, A., Quartieri, E., Gasparini, E., Iotti, S., Baricchi, R., & Merolle, L. (2021) · Diagnostics · doi:10.3390/diagnostics11040727 · Cited by 11 · see citing works
Recent progress in materials used towards corrosion protection of Mg and its alloys
Ghazanfari, H., Hasanizadeh, S., Eskandarinezhad, S., Hassani, S., Sheibani, M., Torkamani, A. D., & Fakić, B. (2020) · Journal of Composites and Compounds · doi:10.29252/jcc.2.4.5 · Cited by 11 · see citing works
“Mg is also a cofactor for different enzymes in the body and acts as a stabilizer for the structures of RNA and DNA [65-70].”
BackgroundKuo, H.-Y., Liang, C., Tsai, S., Chen, T., Chu, C., & Chen, M. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph19148739 · Cited by 11 · see citing works
“In addition, PPI usage is associated with hypomagnesemia [37], and some studies have demonstrated a link between hypomagnesemia and T2DM by altering cellular glucose transport [38].”
BackgroundMagnesium and Micro-Elements in Older Persons
Veronese, N., & Barbagallo, M. (2021) · Nutrients · doi:10.3390/nu13030847 · Cited by 11 · see citing works
Elnenaei, M. O., Thoni, A. J., & Eissa, M. (2022) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2022.03.003 · Cited by 11 · see citing works
Oral magnesium supplementation for leg cramps in pregnancy—An observational controlled trial
de Araújo, C. A. L., de Lorena, S. B., Cavalcanti, G. C. D. S., Leão, G. L. D. S., Tenório, G. P., & Alves, J. G. B. (2020) · PLoS ONE · doi:10.1371/journal.pone.0227497 · Cited by 10 · see citing works
“Magnesium therapy has been shown to be effective in eclampsia-related seizures [6].”
BackgroundSagar, A. N., Kalburgi, V., Vagha, J. D., Taksande, A. M., Meshram, R. J., & Lohiya, S. B. (2024) · Cureus · doi:10.7759/cureus.66643 · Cited by 9 · see citing works
“Neurologically, patients may present with symptoms such as muscle weakness, seizures, and increased neuromuscular excitability, leading to tetany and tremors [18].”
BackgroundMeerman, M., Buijser, M., van den Berg, L., van den Heuvel, A.-M., Hoohenkerk, G. J. F., van Driel, V., Munsterman, L., de Vroege, R., Bailey, M., Bellomo, R., et al. (2024) · Trials · doi:10.1186/s13063-024-08368-3 · Cited by 9 · see citing works
“The precise mechanistic underpinnings of the magnesium-arrhythmia interplay remain incompletely elucidated but may involve modulation of calcium channel function and the sodium–potassium membrane pump [11].”
BackgroundAlbert, A., Hinkel, U. P., Bohlender, T., Stieger, P., Braun-Dullaeus, R. C., & Albert, C. (2025) · Kidney Medicine · doi:10.1016/j.xkme.2025.101046 · Cited by 9 · see citing works
“18 Repeated intravenous (i.v.) injection of magnesium sulfate 50% (equivalent to 486 mg/20 mmol of magnesium) may be necessary to achieve a stable increase of Ca 2 + , and consecutive normalization of PTH levels.”
InfluentialHypokalemic Cardiac Arrest: Narrative Review of Case Reports and Current State of Science
Lloyd, C., Mohar, C., & Priano, J. (2022) · Journal of Emergency Nursing · doi:10.1016/j.jen.2021.12.008 · Cited by 9 · see citing works
Paroxysmal Tremor and Vertical Nystagmus Associated with Hypomagnesemia
Marsé, C., Druesne, V., & Giordana, C. (2020) · Movement Disorders Clinical Practice · doi:10.1002/mdc3.13057 · Cited by 8 · see citing works
“Hypomagnesemia may have different causes, including low intake, pathological redistribution (ie, refeeding syndrome or treatment of diabetic ketoacidosis), and increased loss, for example, via the kidney (familial causes or acquired because of medication associated with hypercalcemia or as a result of alcohol abuse) o…”
Background“AMP plus”: Immunostimulant-Inspired Design Based on Chemotactic Motif-(PhHAhPH)n
Zhu, Y., Xu, Y., Yan, J., Fang, Y., Dong, N., & Shan, A. S. (2023) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.3c09353 · Cited by 8 · see citing works
Impact of SGLT2 Inhibitors on Magnesium in Kidney Transplant Patients with and Without Diabetes
Secondulfo, C., Vecchione, N., Russo, D., Hamzeh, S., Iacuzzo, C., Apicella, L., Pietro, R. A. D., Pisani, A., Amicone, M., Círillo, M., et al. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26072904 · Cited by 7 · see citing works
“…of restoring serum Mg 2+ in kidney patients: hypomagne-semia is associated with hypertension, cardiovascular disease and cerebrovascular events, and osteoporosis [4]; some authors even suggest a pre-emptive initiation of SGLT2i therapy in order to prevent the development of PTDM in KTRs [20].”
Merschmann, R., Burgmer, C., Eckert, G. P., & Wagner, A. E. (2025) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.70227 · Cited by 7 · see citing works
Hypomagnesemia: A Clinical and Nutritional Update
Papagiannidou, A., Mitropoulou, M., Papantzikos, K., Petropoulou, D., Tsilingiris, D., Magkos, F., & Dalamaga, Μ. (2026) · Current Nutrition Reports · doi:10.1007/s13668-026-00745-5 · Cited by 7 · see citing works
“Other important reasons behind poor attention on this ion include the inadequate comprehension of its physiology and the clinical presentation of hypomagnesemia appearing only when magnesium levels are significantly depleted [ 3].”
InfluentialOral magnesium reduces levels of pathogenic autoantibodies and skin disease in murine lupus
Verlato, A., Laragione, T., Bin, S., Kim, R. H., Salem, F. E., Gulko, P. S., & Cravedi, P. (2024) · BMC Immunology · doi:10.1186/s12865-024-00650-y · Cited by 7 · see citing works
“Magnesium has a central role in many intracellular functions [5, 6].”
BackgroundLima, F. D. S., Makiyama, E. N., Hastreiter, A. A., Castelhano, A. B. D. S., & Fock, R. A. (2021) · Clinical Nutrition · doi:10.1016/j.clnu.2021.01.001 · Cited by 7 · see citing works
Li, Q., Hu, X., Li, G., Li, D., Ao, Q., & Zhou, F. (2024) · Aging Clinical and Experimental Research · doi:10.1007/s40520-024-02872-x · Cited by 6 · see citing works
Sankova, M. V., Kytko, O. V., Meilanova, R. D., Vasil’ev, Y. L., & Nelipa, M. V. (2020) · Research Results in Pharmacology · doi:10.3897/rrpharmacology.6.59407 · Cited by 6 · see citing works
“…> magnesium taurate > magnesium aspartate > magnesium aspartate + potassium aspartate > magnesium pyroglutamate (pidolate) > magnesium glycinate > magnesium citrate > magnesium orotate > magnesium lactate (Spasov and Kosolapov 2017; Ahmed and Mohammed 2019; Ates et al. 2019; Eremenko et al. 2019).”
BackgroundInfluentialHypomagnesemia in intestinal lymphangiectasia: a case report and review of the literature
Feng, H., Zou, L., Zhai, X., Zhang, S., & Li, J. (2022) · BMC Gastroenterology · doi:10.1186/s12876-022-02318-6 · Cited by 6 · see citing works
“In addition, one-third of the active form (as opposed to the storage form) of body magnesium is bound to albumin [3].”
BackgroundXie, J.-Z., Huang, Y., Zheng, X.-F., Feng, R., Li, X., Zheng, Z.-G., Jiang, B.-J., Du, S., Chen, H., & Xu, Y. (2024) · BMC Public Health · doi:10.1186/s12889-023-17615-2 · Cited by 6 · see citing works
“Thus, Mg disorder, probably owing to an excessive dietary intake of Mg, pathological problems (e.g., abnormal renal wasting), or excessive use of drugs (e.g., diuretics) [43], would give rise to serious consequences or dramatic effects on metabolism.”
BackgroundSankova, M. V., Nikolenko, V. N., Oganesyan, M. V., Sankov, S. V., Sinelnikov, M. Y., Suslov, A. V., Trishina, A. S., Zharikova, T. S., Pontes‐Silva, A., & Zharikov, Y. O. (2024) · Sport Sciences for Health · doi:10.1007/s11332-024-01179-8 · Cited by 6 · see citing works
“…the degree of alimentary hyomagne-semia compensation in erythrocytes in the following order: Mg aspartate + B6 > Mg lactate + B6 = Mg aspartate > Mg taurate > Mg aspartate > Mg aspartate + potassium aspar - aginate > pyroglutamate (pidol) > Mg glycinate > Mg citrate > Mg orotate > Mg lactate [91].”
Kim, O., Kim, K., Park, S., Yang, H., Kim, H., Ro, W., & Lee, C. (2023) · Journal of Veterinary Internal Medicine · doi:10.1111/jvim.16963 · Cited by 6 · see citing works
Thyrotoxic Hypokalemic Periodic Paralysis: Pathophysiological Mechanisms
Qing, G., Zakaria, W. N. A., Rom, F. Z. M., Nik, W. N. F. H. W., Zulkeflee, H. A., & Rahim, S. N. A. (2025) · Endocrinology and Metabolism · doi:10.3803/enm.2025.2554 · Cited by 5 · see citing works
“Magnesium deficiency may contribute to hypokalemia by enhancing renal potassium loss via disinhibition of renal outer medullary potassium channel (ROMK) in the distal nephron [41].”
Cation-Binding of Glutamate in Aqueous Solution
Friesen, S., Kruchinin, S. E., Fedotova, M. V., & Buchner, R. (2024) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.4c02373 · Cited by 5 · see citing works
The role of gut flora-driven Th cell responses in preclinical rheumatoid arthritis
Chen, S., Dan, L., Li, X., He, Q., Hu, D., & Gao, Y. (2025) · Journal of Autoimmunity · doi:10.1016/j.jaut.2025.103426 · Cited by 5 · see citing works
Trace element magnesium: a key player in hypertension management
Parsanathan, R. (2023) · Hypertension Research · doi:10.1038/s41440-023-01404-w · Cited by 5 · see citing works
Clinical Guideline for Detection and Management of Magnesium Deficiency in Ambulatory Care
Colaneri-Day, S., & Rosanoff, A. (2025) · Nutrients · doi:10.3390/nu17050887 · Cited by 5 · see citing works
“Traditional and current HCP training does not incorporate the identification of Mg deficit in the diagnosis of acute and chronic diseases [6].”
Laragione, T., Harris, C. L., & Gulko, P. S. (2024) · Nutrients · doi:10.3390/nu16234247 · Cited by 5 · see citing works
“Magnesium (Mg) is the second most abundant intracellular cation in the human body and is involved in several biochemical functions including enzymatic activity and gene transcription [5].”
Dias, R. S. C., Brito, D. J. D. A., Santos, E. M. D., Costa, R. C. D. O., Fontenele, A. M. M., Hortegal, E. V., Lages, J. S., dos Santos, A. M., Santos, E. J. F., Carneiro, É. C. R. D. L., et al. (2020) · International Journal of Nephrology and Renovascular Disease · doi:10.2147/ijnrd.s282106 · Cited by 5 · see citing works
Diagnosis and outpatient management of Gitelman syndrome from the first trimester of pregnancy
Lim, M., & Gannon, D. (2021) · BMJ Case Reports · doi:10.1136/bcr-2021-241756 · Cited by 5 · see citing works
Neurological aspects of electrolyte disorders
Howard, R., Baheerathan, A., Brown, R. L., Spillane, J. E., & Waraich, M. (2025) · Practical Neurology · doi:10.1136/pn-2023-003801 · Cited by 9 · see citing works
A Proposed Scale to Assess Magnesium Status Using Serum Calcium and Magnesium Ratios
Rosanoff, A., von Ehrlich, B., & Nelson, D. J. (2025) · Nutrients · doi:10.3390/nu17233671 · Cited by 4 · see citing works
Larimi, A. S., Jafari, H., & Sadeghzadeh, A. (2024) · JOM · doi:10.1007/s11837-024-06932-5 · Cited by 4 · see citing works
Genome-wide association study of serum magnesium in type 2 diabetes
Oost, L. J., Slieker, R. C., Blom, M. T., Hart, L. M. ‘., Hoenderop, J. G. J., Beulens, J. W. J., & de Baaij, J. H. F. (2024) · Genes & Nutrition · doi:10.1186/s12263-024-00738-5 · Cited by 4 · see citing works
“The prevalence of hypomagnesemia is between 10 and 45%, which is 10 times higher in people with type 2 diabetes mellitus compared to the healthy population [6–8].”
BackgroundFamilial hypomagnesemia with hypocalcemia: a rare cause of infantile seizures
Srinivasan, R., Ninama, A. C., Krishna, S., & Vasudevan, A. (2022) · CEN Case Reports · doi:10.1007/s13730-022-00734-x · Cited by 4 · see citing works
“It also regulates the movement of sodium and potassium across cell membranes [2].”
BackgroundMassive Transfusion Increases Serum Magnesium Concentration
Malinowska, J., Małecka‐Giełdowska, M., Pietrucha, K., Górska, G., Kogut, D., & Ciepiela, O. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12155157 · Cited by 4 · see citing works
Marushko, Y. V., Hyshchak, T. V., Dmytryshyn, O. A., Dmytryshyn, B. Y., & Myka, M. Y. (2023) · Modern pediatrics Ukraine · doi:10.15574/sp.2023.133.90 · Cited by 4 · see citing works
The Potential Role of Glutamate Receptors and their Antagonists or Modulators in Migraine Therapy
Tsai, C.-H., Lai, M., & Huang, C. (2025) · Current Neuropharmacology · doi:10.2174/1570159x23666250403124115 · Cited by 3 · see citing works
Ionized calcium and ionized magnesium disturbances in dogs and cats with septic peritonitis
Debie, C., Giberto, L., Noël, S. M., Paepe, D., & Gommeren, K. (2025) · Frontiers in Veterinary Science · doi:10.3389/fvets.2025.1550701 · Cited by 3 · see citing works
“Conditions such as trauma (71), neoplasia (72), renal failure (17, 72, 73), hyperthyroidism (64), pancreatitis (24, 74–76), hypoadrenocorticism (72), and diabetes mellitus (24, 77, 78), are known to affect iCa and iMg values.”
InfluentialPasqualetti, S., Chibireva, M. D., Birindelli, S., & Panteghini, M. (2021) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2021.03.016 · Cited by 3 · see citing works
Formulation and evaluation of magnesium sulphate nanoparticles for improved CNS penetrability
Mathew, A. A., Mohapatra, S., & Panonnummal, R. (2022) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-022-02356-7 · Cited by 3 · see citing works
“Magnesium oxide, carbonate, sulphate, citrate, lactate, chloride and aspartate are commonly available magnesium supplements (Ahmed and Mohammed 2019).”
BackgroundTirani, S. A., Rouhani, P., & Saneei, P. (2025) · Nutrition Reviews · doi:10.1093/nutrit/nuaf014 · Cited by 3 · see citing works
Magtaan, J. K., Fitzpatrick, B., & Murphy, R. P. (2020) · Current Pharmaceutical Design · doi:10.2174/1381612826666201210112119 · Cited by 3 · see citing works
Public Health Perspective on Magnesium
Šoher, L., & Banjari, I. (2021) · Journal of Applied Health Sciences · doi:10.24141/1/7/2/10 · Cited by 3 · see citing works
Hypomagnesaemia – One Cause To Remember!
Viegas, A. F., Lopes, A. F. M., de Almeida, C. L., Ennis, G., & Tavares, J. P. (2022) · European Journal of Case Reports in Internal Medicine · doi:10.12890/2022_003637 · Cited by 3 · see citing works
“Hypokalaemia is frequently seen resulting from different mechanisms: hypoparathyroidism due to impaired PTH release caused by hypomagnesaemia; bone-PTH resistance; or vitamin D deficiency caused by decreased vitamin D renal conversion, either by decreased PTH levels or by a direct effect of magnesium depletion on the…”
BackgroundInfluential
- Authors
- Ahmed, F., & Mohammed, A.
- Affiliations
- OSF Saint Anthony Medical Center (US)
- Advocate Illinois Masonic Medical Center (US)
- Corresponding author
- Ahmed, Faheemuddin
- ORCID
- Mohammed, Abdul
- Venue
- Medical Sciences
- Publisher
- MDPI AG
- Published
- 2019-04-04
- Volume
- 7
- Issue
- 4
- Pages
- 56
- ISSN
- 2076-3271 (ISSN-L)
- PMC
- PMC6524065
- OpenAlex
- W2926579042
- Cited by
- 186
- References
- 46
- Citations by year
- 2026: 14 · 2025: 28 · 2024: 31 · 2023: 32 · 2022: 28 · 2021: 29 · 2020: 24
- FWCI
- 2.75
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Medical Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Magnesium in Health and Disease
- Physical Sciences › Materials Science › Biomaterials › Magnesium Alloys: Properties and Applications
- Physical Sciences › Materials Science › Materials Chemistry › Magnesium Oxide Properties and Applications
- Keywords
- magnesium, hypomagnesemia, magnesium physiology, electrolytes, intracellular cations, clinical features, incidence, treatment
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