American Diabetes Association
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Associations of Habitual Calcium Supplementation with Risk of Cardiovascular Disease and Mortality in Individuals with and without Diabetes

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posted on 2023-07-25, 00:10 authored by Zixin Qiu, Qi Lu, Zhenzhen Wan, Tingting Geng, Rui Li, Kai Zhu, Lin Li, Xue Chen, An Pan, JoAnn E. Manson, Gang Liu


Objectives: To prospectively examine the associations of habitual calcium supplementation with cardiovascular diseases (CVD) events and mortality in individuals with and without diabetes.

Methods: The main analysis included 434,674 participants from the UK Biobank. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Interactions of calcium supplement use with diabetes status were tested on multiplicative and additive scales.

Results: Over a median follow-up of 8.1 and 11.2 years, 26,374 incident CVD events and 20,526 deaths were documented, respectively. After multivariable adjustment, habitual calcium supplementation was significantly associated with higher risks of CVD incidence (HR: 1.34 [95% CI:1.14, 1.57]), CVD mortality (HR: 1.67 [95% CI: 1.19, 2.33]), and all-cause mortality (HR: 1.44 [95% CI: 1.20, 1.72]) in participants with diabetes, whereas no significant association was observed in participants without diabetes (HR: 0.97 [95% CI: 0.92, 1.03] for CVD incidence; HR: 1.05 [95% CI: 0.90, 1.23] for CVD mortality; HR: 1.02 [95% CI: 0.96, 1.09] for all-cause mortality). Significant multiplicative and additive interactions were found between habitual calcium supplementation and diabetes status on risks of CVD events and mortality (all P interaction<0.05). In contrast, no significant interactions were observed between dietary or serum calcium and diabetes status.

Conclusions: Habitual use of calcium supplements was significantly associated with higher risk of CVD events and mortality in people with diabetes, but not in people without diabetes. Further studies are needed to balance potentially adverse effects of calcium supplement against likely benefits, particularly among patients with diabetes.


Gang Liu was funded by grants from National Nature Science Foundation of China (82273623 and 82073554), the Hubei Province Science Fund for Distinguished Young Scholars (2021CFA048), and the Fundamental Research Funds for the Central Universities (2021GCRC076). An Pan was supported by grants from National Nature Science Foundation of China (81930124 and 82021005), and the Fundamental Research Funds for the Central Universities (2021GCRC075). The funders had no role in the study design or implementation; data collection, management, analysis, or interpretation; manuscript preparation, review, or approval; or the decision to submit the manuscript for publication.