All-cause and cause-specific mortality risks associated with calcium supplementation with or without vitamin D: A nationwide population-based study.

Background: Current evidence regarding the mortality outcomes associated with calcium supplementation with or without low-dose vitamin D is conflicting.

Objectives: To investigate the effects of calcium supplementation with or without vitamin D on all-cause and cause-specific mortalities in a large-scale cohort.

Methods: This study used data from the Korean National Health Insurance System database and National Death Registry. A total of 27,846 participants aged >55 years who had taken calcium supplements with or without vitamin D for at least 90 days (calcium supplementation only [CaO], n = 6256; calcium supplementation in combination with vitamin D [CaD], n = 21,590) were matched in a 1:1 ratio to those who did not take calcium or vitamin D supplements (control group) using propensity scores.

Results: No difference in all-cause mortality risk was found between the CaO and control groups: (adjusted hazard ratio [HR] = 1.00; 95% confidence interval [CI]: 0.92-1.10). However, all-cause mortality was lower in the CaD group (HR = 0.85; 95% CI: 0.80-0.89) compared with that in the control group. Mortality risk associated with cardiovascular disease (CVD) was decreased in the CaD group when the daily vitamin D dose received was less than 1000 IU (HR = 0.72; 95% CI: 0.64-0.81). Subgroup analysis showed significant effect of vitamin D with calcium in individuals who were female, aged ≥65 years or had previous history of cancer or CVD.

Conclusion: In combination with calcium, vitamin D supplementation provides better outcomes for all-cause mortality, particularly CVD-associated mortality, in a duration-dependent manner.