Hypomagnesemia: A Clinical and Nutritional Update

Hypomagnesemia, defined as low serum/plasma magnesium concentration, is a highly prevalent yet underrecognized electrolyte disorder with extensive clinical, metabolic, and nutritional implications. This review provides an updated synthesis of magnesium physiology, dietary determinants, homeostatic regulation, diagnostic challenges, and therapeutic strategies, with particular emphasis on recent meta-analyses and large-scale epidemiological evidence linking hypomagnesemia to multisystem disease. Accumulating evidence has shown consistent associations between low serum or dietary magnesium and increased risk of cardiometabolic disorders (hypertension, type 2 diabetes mellitus, metabolic syndrome, and cardiovascular disease), neuropsychiatric conditions (migraine, depression, cognitive impairment, and dementia), osteoporosis, immune dysregulation, and adverse outcomes in hospitalized, critically ill, and chronic kidney disease patients. Mechanistic studies have clarified the roles of TRPM6/7 channels, tight junction claudins, and basolateral magnesium transporters in intestinal and renal magnesium handling, elucidating pathways underlying both inherited and acquired deficiencies. Research has also highlighted the contribution of modern dietary patterns, food processing, mineral-depleted drinking water, medication use (notably proton pump inhibitors, diuretics and chemotherapeutic agents), and gut microbiome alterations to widespread subclinical deficiency. Meta-analyses of RCTs indicate that magnesium supplementation confers modest but clinically relevant improvements in blood pressure, glycemic control, inflammatory markers, endothelial function, migraine frequency, and depressive symptoms, particularly in individuals with baseline hypomagnesemia. However, serum magnesium remains an insensitive biomarker of total body magnesium status, and consensus on optimal diagnostic thresholds and replacement strategies is lacking. Magnesium deficiency contributes to a wide spectrum of multisystem disorders, and is driven by dietary insufficiency, gastrointestinal and renal losses, medication use, chronic disease, and altered microbiome function. Meta-analytic evidence supports its role as a modifiable risk factor across cardiovascular, metabolic, neurological, skeletal, and immune disorders. Dietary modification, optimized supplementation, and correction of underlying causes of deficiency remain central to management. Future research should focus on improved diagnostic tools, personalized dosing approaches and long-term outcomes of magnesium repletion. Enhancing clinical awareness and integrating magnesium evaluation into routine care may reduce the growing burden of hypomagnesemia.