Long-Term Effect of Randomization to Calcium and Vitamin D Supplementation on Health in OlderWomen

Cynthia A. Thomson, Aaron K. Aragaki, Ross L. Prentice, Marcia L. Stefanick, Jo Ann E. Manson, Jean Wactawski-Wende, Nelson B. Watts, Linda Van Horn, James M. Shikany, Thomas E. Rohan, Dorothy S. Lane, Robert A. Wild, Rogelio Robles-Morales, Aladdin H. Shadyab, Nazmus Saquib, Jane Cauley

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Background: Although calcium and vitamin D (CaD) supplementation may affect chronic disease in older women, evidence of long-term effects on health outcomes is limited. Objective: To evaluate long-term health outcomes among postmenopausal women in the Women's Health Initiative CaD trial. Design: Post hoc analysis of long-term postintervention follow-up of the 7-year randomized intervention trial of CaD. (ClinicalTrials.gov: NCT00000611) Setting: A multicenter (n 40) trial across the United States. Participants: 36 282 postmenopausal women with no history of breast or colorectal cancer. Intervention: Random 1:1 assignment to 1000 mg of calcium carbonate (400 mg of elemental calcium) with 400 IU of vitamin D3 daily or placebo. Measurements: Incidence of colorectal, invasive breast, and total cancer; disease-specific and all-cause mortality; total cardiovascular disease (CVD); and hip fracture by randomization assignment (through December 2020). Analyses were stratified on personal supplement use. Results: For women randomly assigned to CaD versus placebo, a 7% reduction in cancer mortality was observed after a median cumulative follow-up of 22.3 years (1817 vs. 1943 deaths; hazard ratio [HR], 0.93 [95% CI, 0.87 to 0.99]), along with a 6% increase in CVD mortality (2621 vs. 2420 deaths; HR, 1.06 [CI, 1.01 to 1.12]). There was no overall effect on other measures, including all-cause mortality (7834 vs. 7748 deaths; HR, 1.00 [CI, 0.97 to 1.03]). Estimates for cancer incidence varied widely when stratified by whether participants reported supplement use before randomization, whereas estimates on mortality did not vary, except for CVD mortality. Limitation: Hip fracture and CVD outcomes were available on only a subset of participants, and effects of calcium versus vitamin D versus joint supplementation could not be disentangled. Conclusion: Calcium and vitamin D supplements seemed to reduce cancer mortality and increase CVD mortality after more than 20 years of follow-up among postmenopausal women, with no effect on all-cause mortality.

Original languageEnglish (US)
Pages (from-to)428-438
Number of pages11
JournalAnnals of internal medicine
Volume177
Issue number4
DOIs
StatePublished - Apr 1 2024

ASJC Scopus subject areas

  • Internal Medicine

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