Liproxstatin-1 However, given concern about an elevation in MI with calcium use based on other data sources [8], one should

keep in mind the possibility of an early MI elevation, but this hypothesis derives little support from WHI data. The analyses of CaD trial data suggest possible reductions for invasive PF-573228 cell line cancer with supplementation [3, 8]. Such HR reductions are nominally significant for invasive breast cancer (P = 0.02) and for total invasive cancer (P = 0.03) among women not using personal supplements, and these reductions persisted following restriction to adherent women. However, corresponding HR reductions were not significant for the trial cohort as a whole. The fact that HRs for both breast cancer and total cancer differed significantly between learn more the personal supplements and no personal supplements groups could reflect HRs that are below unity

at lower calcium and vitamin D doses, and that flatten out at larger doses so that women using personal supplements may have already achieved any cancer risk reduction from supplementation, with little or no further benefit from further supplementation. While this possibility is intriguing, and potentially of public health importance, breast and total cancer were not among the designated primary or secondary outcomes for the CaD, so multiple testing considerations, in conjunction with subset analysis and other [3] considerations cause us to take a cautious interpretation of these analyses. Hence, we regard the WHI data as merely suggestive of invasive breast and total invasive cancer risk reduction with available data. Consistent with our previous report [7], we find no statistically significant association between CaD supplementation and death Enzalutamide datasheet in the CaD trial overall or in the subgroup not using personal supplements. There was no evidence in either the CaD trial or the OS that long-term

(≥5 years) CaD supplementation reduced the risk of death. Specifically, the CaD intervention did not affect death from coronary heart disease where the hazard ratio was 0.99 (95 % CI, 0.71, 1.38) [7]. With this background, the only documented risk associated with the randomized intervention in the CaD trial is a modest elevation (HR of 1.17, 95 % CI from 1.02 to 1.34) in urinary tract stone occurrence that did not differ significantly between the personal supplements and no personal supplements subsets. Observational data have several limitations in addressing these types of research questions. For outcomes, such as hip fractures and heart disease, where calcium and/or vitamin D from foods or supplements may have developed a reputation as potential disease preventatives, observational studies not only need to control for standard confounding factors, but also for factors related to confounding by indication since persons at elevated risk for these diseases may self-select, or preferentially be prescribed, these supplements.