After multivariable adjustment, a high total calcium intake was also associated with a higher mortality risk (table 2). The shift from a lower to a higher risk with the multivariable model was mainly the consequence of the adjustment for use of calcium containing supplements (see supplementary table 1). In addition, mortality rates were higher among women with an intake below 600 mg/day (table 2). The tendency of a U-shaped association between both dietary and total calcium intake with deaths from all causes, cardiovascular disease, and ischaemic heart disease is also visualised by the pattern of the spline curves in figure 2⇓, a pattern that was not apparent for stroke mortality. However, to deal further with possible bias introduced by using time updated information in the models, sensitivity analyses were carried out. Firstly, only baseline data were included, without updating with information from the second questionnaire (see supplementary table 2). This analysis indicated a higher risk of death with high dietary calcium intakes but not with low intakes. Secondly, a causal inference analytical model was used. Although hampered by a lower precision (see supplementary table 3), the results for the high dietary calcium intake level are essentially similar to those obtained by ordinary Cox’s regression analysis (table 2 and supplementary table 2) but the estimates for women with low dietary calcium intakes were
attenuated. Moreover, mortality estimates for women with both low and high total calcium intakes were attenuated compared with the time dependent Cox regression model.
Calcium containing supplements were used by one fourth (10 055/38 984) of the study population in 1997. The largest source of supplemented calcium was from multivitamins with minerals (120 mg per tablet; 74% of supplement users). Most women taking calcium tablets were also regular users of multivitamins. The average dietary intake of calcium was similar in calcium supplement users, both at baseline (users reported 6 mg lower dietary calcium intake; 95% confidence interval −2 to 13 mg) and at the second investigation in 1997 (users reported 6 mg lower intake; 0 to 13 mg). Use of calcium containing supplements in 1997 was not associated with death from cardiovascular disease or ischaemic heart disease (see supplementary table 4).
Women who had a high dietary intake of calcium exceeding 1400 mg/day and additionally used calcium supplements had a higher mortality rate than women with a similarly high intake of calcium but without taking supplements (table 3⇓). Thus, among calcium tablet users (500 mg calcium per tablet), a high dietary calcium intake (>1400 mg/day) conferred a multivariable adjusted hazard ratio of 2.57 (95% confidence interval 1.19 to