Calcium-Magnesium Balance—Clinical Implications for Global Human Health

Magnesium is essential for vitamin D₃ metabolism and optimum function, supporting enzymes that synthesize 25(OH) D and calcitriol and facilitating receptor binding. Optimizing the Ca: Mg ratio likely enhances vitamin D efficacy and improves outcomes. Beyond this, Mg is vital for G-protein-coupled receptor function, CYP450 enzyme activity, activation of B vitamins, epigenetic methylation, glucose metabolism, and mitigating oxidative stress and inflammaging. Assessing serum Mg (mmol/L) offers a more physiologically relevant measure than dietary intake (mg/day). Mean ionized Ca and Mg levels yield an iCa: iMg ratio within the optimal range; however, since Mg is distributed in both plasma and red blood cells while Ca is largely extra-cellular, a 3:2 intake ratio may better support homeostasis than the commonly recommended 2:1. Calcium and magnesium function as physiological opposites; their ratio (optimal 1.7-2.6) is a key indicator of health and disease risk. An imbalanced Ca: Mg ratio—outside this range—increases risks for cancer, cardiovascular disease, dementia, infections (including COVID-19 complications), and post-COVID syndrome. Conversely, obesity is both a cause and consequence of Ca: Mg imbalance. Magnesium deficiency likely contributes to the global prevalence of type 2 diabetes, which shares features with aging. Evidence from laboratory reference ranges, NHANES data, and peer-reviewed studies underscores the need for clinical validation of these observations. Globally, magnesium deficiency remains prevalent and understudied in clinical trials. Study data support that maintaining optimal Ca:Mg ratios benefits cancer prevention and common disorders. Optimizing the Ca: Mg ratio is a cost-effective, globally impactful strategy to improve metabolic health and reduce chronic disease risk.