Abstract
Stroke remains a leading cause of death and disability globally, with substantial socioeconomic burdens. Magnesium is essential for cardiovascular and neurological homeostasis, but serum magnesium levels alone inadequately reflect systemic magnesium status. The Magnesium Depletion Score (MDS), a composite metric integrating diuretic use, proton pump inhibitor PPI use, renal function (estimated glomerular filtration rate [eGFR]), and alcohol consumption, provides a more comprehensive assessment of magnesium deficiency. This cross-sectional study analyzed 10,136 US adults from the National Health and Nutrition Examination Survey (1999-2018). MDS was calculated based on 4 components, and weighted multivariable logistic regression models were used to evaluate the association between MDS and stroke risk. Restricted cubic spline analysis was applied to assess dose-response relationships. Higher MDS scores were independently associated with increased stroke risk. After full adjustment for confounders (demographics, lifestyle factors, and cardiovascular comorbidities), each 1-unit increase in MDS was linked to a 27% higher odds of stroke (OR = 1.27, 95%CI: 1.12-1.44). Restricted cubic spline analysis demonstrated a linear dose-response relationship without evidence of a threshold effect. Systemic magnesium depletion, as measured by MDS, is significantly associated with stroke risk. MDS may serve as a practical tool for identifying individuals at elevated risk, underscoring the importance of targeted nutritional interventions and lifestyle modifications in stroke prevention.