Magnesium depletion score and circadian syndrome: Mediated by body mass index

Objective Circadian syndrome (CircS) is a recently defined condition encompassing metabolic, sleep, and mental health disturbances. Magnesium plays a vital role in metabolic and neurological processes, and magnesium depletion score (MDS) has emerged as a practical biomarker for magnesium deficiency. This cross-sectional retrospective study aimed to investigate the association between MDS and CircS in a nationally representative U.S. population. Methods Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2005-2018. MDS was calculated based on diuretic or proton pump inhibitor use, estimated glomerular filtration rate, and alcohol consumption. CircS was diagnosed using a combination of metabolic syndrome components, depressive symptoms, and short sleep duration. Weighted logistic regression models, restricted cubic spline analysis, subgroup analyses, receiver operating characteristic (ROC) curves, and mediation analysis were applied. Results A total of 12,328 participants were included. Higher MDS was significantly associated with an increased risk of CircS (OR = 1.193, 95% CI: 1.099-1.295, P < 0.001). Sensitivity analyses excluding participants with cardiovascular disease confirmed robustness of the findings. Mediation analysis showed that body mass index (BMI) explained 21% (95% CI: 12.98-34%) of the association between MDS and CircS. ROC analysis indicated modest discriminative ability of MDS for CircS (AUC = 0.616). Conclusion This study demonstrates that MDS is positively associated with CircS, and BMI partly mediates this association. These findings suggest that maintaining adequate magnesium levels may help support circadian health. Further longitudinal and mechanistic studies are warranted to validate the clinical applicability of MDS in CircS risk assessment.