Calcium intake and mortality from all causes, cancer, and cardiovascular disease: The Cancer Prevention Study II Nutrition Cohort

Background: Calcium intake may be important for bone health, but its effects on other outcomes, including cardiovascular disease (CVD) and cancer, remain unclear. Recent reports of adverse cardiovascular effects of supplemental calcium have raised concerns. Objective: We investigated associations of supplemental, dietary, and total calcium intakes with all-cause, CVD-specific, and cancerspecific mortality in a large, prospective cohort. Design: A total of 132,823 participants in the Cancer Prevention Study II Nutrition Cohort, who were followed from baseline (1992 or 1993) through 2012 for mortality outcomes, were included in the analysis. Dietary and supplemental calcium information was first collected at baseline and updated in 1999 and 2003. Multivariable-adjusted Cox proportional hazards models with cumulative updating of exposures were used to calculate RRs and 95% CIs for associations between calcium intake and mortality. Results: During a mean follow-up of 17.5 y, 43,186 deaths occurred. For men, supplemental calcium intake was overall not associated with mortality outcomes (P-trend > 0.05 for all), but men who were taking ≥1000 mg supplemental calcium/d had a higher risk of all-cause mortality (RR: 1.17; 95% CI: 1.03, 1.33), which was primarily attributed to borderline statistically significant higher risk of CVD-specific mortality (RR: 1.22; 95% CI: 0.99, 1.51). For women, supplemental calcium was inversely associated with mortality from all causes [RR (95% CI): 0.90 (0.87, 0.94), 0.84 (0.80, 0.88), and 0.93 (0.87, 0.99) for intakes of 0.1 to ,500, 500 to <1000, and ≥1000 mg/d, respectively; P-trend < 0.01]. Total calcium intake was inversely associated with mortality in women (P-trend < 0.01) but not in men; dietary calcium was not associated with all-cause mortality in either sex. Conclusions: In this cohort, associations of calcium intake and mortality varied by sex. For women, total and supplemental calcium intakes are associated with lower mortality, whereas for men, supplemental calcium intake ≥1000 mg/d may be associated with higher all-cause and CVD-specific mortality.