PHARMACOKINETICS AND BIOAVAILABILITY OF MAGNESIUM PREPARATIONS: A COMPREHENSIVE ANALYSIS OF ORGANIC, INORGANIC, AND CHELATED FORMS
DOI:
https://doi.org/10.11603/2312-0967.2026.2.16004Keywords:
magnesium, bioavailability, pharmacokinetics, chelated complexes, magnesium L-threonate, tissue specificity, mineral metabolism, hypomagnesemiaAbstract
Introduction. Magnesium is a critically important intracellular cation acting as a cofactor in over 600 enzymatic reactions and playing a fundamental role in maintaining cellular homeostasis. Given the global prevalence of hypomagnesemia, oral supplementation has become a routine medical practice. However, its clinical efficacy is significantly limited by the highly variable bioavailability of different pharmacological forms of the mineral. The aim of this review is to provide a comprehensive analysis of current scientific data regarding the pharmacokinetics, absorption mechanisms, and tissue specificity of various chemical magnesium compounds.
Materials and methods. A thorough search and narrative analysis of relevant scientific literature (primarily 2015–2025) were conducted using PubMed/MEDLINE, Scopus, Web of Science international electronic databases. The analysis included original in vivo experimental studies, clinical trials on pharmacokinetics and bioequivalence, and systematic reviews.
Results and discussion. The physiological pathways of magnesium absorption (paracellular and transcellular transport via TRPM6/7 channels) and the impact of the chemical structure of salts on their systemic bioavailability were analyzed. It has been established that classical inorganic salts (oxide, sulfate) are characterized by low absorption and pronounced gastrointestinal side effects. In contrast, organic salts (malate, citrate) and amino acid chelates (bisglycinate, acetyl taurate) demonstrate significantly higher absorption rates by utilizing alternative transport pathways. Advanced liposomal (sucrosomial) forms and compounds capable of efficiently crossing the blood-brain barrier (magnesium L-threonate and taurate) provide the highest targeted clinical efficacy.
Conclusions. The need to shift from a "one-size-fits-all" approach to personalized selection of magnesium preparations is well-founded. The prescription of a specific form should be based on specific clinical indications, the need to cross tissue barriers, the synergistic action of cofactors (vitamins B6, D), and the metabolic activity of the carrier anion.
References
Kröse JL, de Baaij JHF. Magnesium biology. Nephrol Dial Transplant. 2024;39(12):1965-1975. doi: 10.1093/ndt/gfae134. DOI: https://doi.org/10.1093/ndt/gfae134
Mooren FC. Magnesium and disturbances in carbohydrate metabolism. Diabetes Obes Metab. 2015;17(9):813-823. doi: 10.1111/dom.12492. DOI: https://doi.org/10.1111/dom.12492
Morais JB, Severo JS, Santos LR, de Sousa Melo SR, de Oliveira Santos R, de Oliveira AR, et al. Role of Magnesium in Oxidative Stress in Individuals with Obesity. Biol Trace Elem Res. 2017;176(1):20-26. doi: 10.1007/s12011-016-0793-1. DOI: https://doi.org/10.1007/s12011-016-0793-1
Feng J, Wang H, Jing Z, Wang Y, Cheng Y, Wang W, et al. Role of Magnesium in Type 2 Diabetes Mellitus. Biol Trace Elem Res. 2020;196(1):74-85. doi: 10.1007/s12011-019-01922-0. DOI: https://doi.org/10.1007/s12011-019-01922-0
Li R, Li Z, Huang Y, Hu K, Ma B, Yang Y. The effect of magnesium alone or its combination with other supplements on the markers of inflammation, OS and metabolism in women with polycystic ovarian syndrome (PCOS): A systematic review. Front Endocrinol (Lausanne). 2022;13:974042. doi: 10.3389/fendo.2022.974042. DOI: https://doi.org/10.3389/fendo.2022.974042
Peng H, Zhao M, Zhang Y, Guo Y, Zhao A. Increased magnesium intake does not mitigate MAFLD risk associated with magnesium deficiency. Sci Rep. 2024;14(1):30386. doi: 10.1038/s41598-024-82203-2. DOI: https://doi.org/10.1038/s41598-024-82203-2
Yamanaka R, Shindo Y, Oka K. Magnesium Is a Key Player in Neuronal Maturation and Neuropathology. Int J Mol Sci. 2019;20(14):3439. doi: 10.3390/ijms20143439. DOI: https://doi.org/10.3390/ijms20143439
Daw CC, Ramachandran K, Enslow BT, Maity S, Bursic B, Novello MJ, et al. Lactate Elicits ER-Mitochondrial Mg2+ Dynamics to Integrate Cellular Metabolism. Cell. 2020;183(2):474-489. doi: 10.1016/j.cell.2020.08.049. DOI: https://doi.org/10.1016/j.cell.2020.08.049
Manger B, Schett G. Magnesium Disorders. N Engl J Med. 2024;391(7):668-669. doi: 10.1056/NEJMc2408312. DOI: https://doi.org/10.1056/NEJMc2408312
Uysal N, Kizildag S, Yuce Z, Guvendi G, Kandis S, Koc B, et al. Timeline (Bioavailability) of Magnesium Compounds in Hours: Which Magnesium Compound Works Best? Biol Trace Elem Res. 2019;187(1):128-136. doi: 10.1007/s12011-018-1351-9. DOI: https://doi.org/10.1007/s12011-018-1351-9
Vermeulen EA, Vervloet MG. Magnesium Administration in Chronic Kidney Disease. Nutrients. 2023;15(3):547. doi: 10.3390/nu15030547. DOI: https://doi.org/10.3390/nu15030547
Zhong XF, Zhou G, Xu SM, Li XM, Xu Y, Liu WL, et al. Pharmacokinetics of Esomeprazole Magnesium After Single Oral Doses in Healthy Subjects: Bioequivalence Study and Food Effects. Clin Pharmacol Drug Dev. 2022;11(11):1308-1313. doi: 10.1002/cpdd.1139. DOI: https://doi.org/10.1002/cpdd.1139
Jin J, Huang C, Zhu C, Feng W, He A, Li T, et al. Pharmacokinetics, Bioequivalence, and Safety of Esomeprazole Magnesium Enteric-Coated Capsules in Healthy Chinese Subjects. Clin Pharmacol Drug Dev. 2023;12(7):691-698. doi: 10.1002/cpdd.1273. DOI: https://doi.org/10.1002/cpdd.1273
Gröber U. Magnesium and Drugs. Int J Mol Sci. 2019;20(9):2094. doi: 10.3390/ijms20092094. DOI: https://doi.org/10.3390/ijms20092094
Workinger JL, Doyle RP, Bortz J. Challenges in the Diagnosis of Magnesium Status. Nutrients. 2018;10(9):1202. doi: 10.3390/nu10091202. DOI: https://doi.org/10.3390/nu10091202
Pardo MR, Garicano Vilar E, San Mauro Martín I, Camina Martín MA. Bioavailability of magnesium food supplements: A systematic review. Nutrition. 2021;89:111294. doi: 10.1016/j.nut.2021.111294. DOI: https://doi.org/10.1016/j.nut.2021.111294
Ates M, Kizildag S, Yuksel O, Hosgorler F, Yuce Z, Guvendi G, et al. Dose-Dependent Absorption Profile of Different Magnesium Compounds. Biol Trace Elem Res. 2019;192(2):244-251. doi: 10.1007/s12011-019-01663-0. DOI: https://doi.org/10.1007/s12011-019-01663-0
Schumacher SA, Toribio RE, Scansen B, Lakritz J, Bertone AL. Pharmacokinetics of magnesium and its effects on clinical variables following experimentally induced hypermagnesemia. J Vet Pharmacol Ther. 2020;43(6):577-590. doi: 10.1111/jvp.12883. DOI: https://doi.org/10.1111/jvp.12883
Ellison DH, Maeoka Y, McCormick JA. Molecular Mechanisms of Renal Magnesium Reabsorption. J Am Soc Nephrol. 2021;32(9):2125-2136. doi: 10.1681/ASN.2021010042. DOI: https://doi.org/10.1681/ASN.2021010042
Di Mario F, Regolisti G, Greco P, Maccari C, Superchi E, Morabito S, et al. Prevention of hypomagnesemia in critically ill patients with acute kidney injury on continuous kidney replacement therapy: the role of early supplementation and close monitoring. J Nephrol. 2021;34(4):1271-1279. doi: 10.1007/s40620-020-00864-4. DOI: https://doi.org/10.1007/s40620-020-00864-4
Werner T, Kolisek M, Vormann J, Pilchova I, Grendar M, Struharnanska E, et al. Assessment of bioavailability of Mg from Mg citrate and Mg oxide by measuring urinary excretion in Mg-saturated subjects. Magnes Res. 2019;32(3):63-71. doi: 10.1684/mrh.2019.0457.
Maier JA, Pickering G, Giacomoni E, Cazzaniga A, Pellegrino P. Headaches and Magnesium: Mechanisms, Bioavailability, Therapeutic Efficacy and Potential Advantage of Magnesium Pidolate. Nutrients. 2020;12(9):2660. doi: 10.3390/nu12092660. DOI: https://doi.org/10.3390/nu12092660
Pajuelo D, Meissner JM, Negra T, Connolly A, Mullor JL. Comparative Clinical Study on Magnesium Absorption and Side Effects After Oral Intake of Microencapsulated Magnesium (MAGSHAPETM Microcapsules) Versus Other Magnesium Sources. Nutrients. 2024;16(24):4367. doi: 10.3390/nu16244367. DOI: https://doi.org/10.3390/nu16244367
Carlos RM, Matias CN, Cavaca ML, Cardoso S, Santos DA, Giro R, et al. The effects of melatonin and magnesium in a novel supplement delivery system on sleep scores, body composition and metabolism in otherwise healthy individuals with sleep disturbances. Chronobiol Int. 2024;41(6):817-828. doi: 10.1080/07420528.2024.2353225. DOI: https://doi.org/10.1080/07420528.2024.2353225
Gröber U, Werner T, Vormann J, Kisters K. Myth or Reality-Transdermal Magnesium? Nutrients. 2017;9(8):813. doi: 10.3390/nu9080813. DOI: https://doi.org/10.3390/nu9080813
Gröber U, Schmidt J, Kisters K. Magnesium in Prevention and Therapy. Nutrients. 2015;7(9):8199-8226. doi: 10.3390/nu7095388. DOI: https://doi.org/10.3390/nu7095388
Mazza E, Maurotti S, Ferro Y, Castagna A, Pujia C, Sciacqua A, et al. Magnesium: Exploring Gender Differences in Its Health Impact and Dietary Intake. Nutrients. 2025;17(13):2226. doi: 10.3390/nu17132226. DOI: https://doi.org/10.3390/nu17132226
Downloads
Published
Issue
Section
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
The authors who publish their materials in this journal agree with the following terms:
- Authors reserve the right to authorship of their work and assign to the journal the right to first publish this work under the terms of the Creative Commons Attribution License, which allows other persons to freely distribute the published work with a mandatory reference to the authors of original work and the first publication of work in this journal
. - Authors have the right to make independent extra-exclusive work agreements in the form they are published by this journal (for example, posting work in an electronic repository of an institution or publishing as part of a monograph), provided that the link to the first publication of the work in this journal is maintained.
Journal policy allows and encourages publication of manuscripts on the Internet (for example, in institutions repositories or on personal websites), both before the publication of this manuscript and during its editorial review, as it contributes to productive scientific discussion and positively affects the efficiency and dynamics of the citation of the published work (see The Effect of Open Access).
