Assessing the journey of calcium supplementation: A mendelian randomization study on the causal link between calcium levels and sleep disorders

Sleep disorder is a growing concern, and calcium supplementation is often recommended as a potential intervention for sleep disorders. However, the causal relationship between calcium levels and the incidence of sleep disorders remains unclear. Mendelian randomization techniques utilizing genetic variants that affect calcium levels, can provide valuable insights into causality. This study aims to examine the association between calcium levels and sleep disorders in a diverse population that includes both adolescents and adults, and investigate the effects of calcium levels on sleep disorders. Mendelian randomization analysis was conducted using data from UK Biobank and FinnGen datasets. The inverse-variance weighting (IVW) was selected as the primary method. In addition, traditional mediation analysis was performed on a subset of the NHANES data spanning from 2007 to 2018. Our findings provide evidence supporting a causal relationship between calcium intake and reduced risk of sleep disorders (beta = -0.079, SE = 0.0395, P = 0.0457). While not reaching statistical significance, other MR methods such as weighted median and Mr-Egger exhibited similar directional trends. Analysis of the NHANES cohort revealed a negative association between calcium levels and the prevalence of sleep disorders in male, black, and physically active populations. However, this association was not observed in other demographic groups. Our results suggested that there is no significant correlation between calcium levels and sleep disorder in non-exercise populations. This raises concerns about the long-term high-dose calcium supplementation in clinical practice, which requires further investigation.