Mechanisms of Magnesium Transport Through Cell Membranes: The Primacy of the Free Divalent Cation and Implications for Magnesium Supplementation

Magnesium (Mg2+) is the second most abundant intracellular cation and an essential cofactor for more than 600 enzymatic reactions. Commercial claims that particular magnesium salts preferentially deliver magnesium to the brain, heart or muscle raise a mechanistic question: do established transport pathways support selective delivery of an intact magnesium complex? This narrative review examines the dissolution of magnesium salts in the gastrointestinal tract, paracellular and transcellular intestinal absorption, plasma magnesium speciation, the transport and regulatory proteins involved in cellular magnesium handling, and selected formulation-comparison studies. Magnesium is absorbed as the free divalent cation Mg2+, and the anion of an ingested salt is handled independently. In plasma, approximately 55% of magnesium is ionised, 30% is bound to albumin and 15% is complexed with small anions. All characterised magnesium transport proteins, including TRPM6, TRPM7, SLC41A1, CNNM proteins, MagT1 and MRS2, handle the free Mg2+ ion. The literature reviewed does not establish a pathway that recognises an ingested magnesium–ligand complex and delivers it selectively to a particular organ. Supplements may nevertheless differ in dissolution, gastrointestinal tolerability, systemic exposure and independent effects of the anion. Claims of organ-specific magnesium delivery based on salt form therefore lack a demonstrated mechanistic basis.