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Long-Term Effect of Calcium and Vitamin D Supplementation on Mortality in Older Women
TAKE-HOME MESSAGE
- In this long-term extension of the Women’s Health Initiative Calcium and Vitamin D randomized controlled trial, initial randomization to treatment with 1000 mg of calcium carbonate combined with 400 IU of vitamin D3 (CaD) was associated with a 7% reduction in the risk of cancer mortality but a 6% increase in the risk of cardiovascular mortality after a median follow-up period of 22.3 years. The intervention had no effect on the risk of all-cause mortality.
- This analysis highlights the possibility of delayed effects of CaD supplementation in reducing cancer mortality and increasing cardiovascular mortality risks in postmenopausal women, with a potential importance for shared decision–making regarding CaD supplementation.
abstract
This abstract is available on the publisher's site.
Access this abstract nowBACKGROUND
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.
PRIMARY FUNDING SOURCE
National Heart, Lung, and Blood Institute of the National Institutes of Health.
Additional Info
Disclosure statements are available on the authors' profiles:
Long-Term Effect of Randomization to Calcium and Vitamin D Supplementation on Health in Older Women : Postintervention Follow-up of a Randomized Clinical Trial
Ann. Intern. Med 2024 Mar 12;[EPub Ahead of Print], CA Thomson, AK Aragaki, RL Prentice, ML Stefanick, JE Manson, J Wactawski-Wende, NB Watts, L Van Horn, JM Shikany, TE Rohan, DS Lane, RA Wild, R Robles-Morales, AH Shadyab, N Saquib, J CauleyFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Calcium and vitamin D supplementation
This arm of the Women’s Health Initiative (WHI) Study followed 36,282 postmenopausal women for a median of 22.3 years. The women were randomized to receive 1000 mg of calcium carbonate (400 mg elemental calcium) and 400 IU of vitamin D3 or placebo daily.
The primary outcomes were overall mortality and mortality from cancer and heart disease. The findings were mixed. There was a 7% reduction in cancer mortality and a 6% increase in mortality from heart disease; however, there was no difference in overall mortality.
What does this mean clinically?
Avoid calcium supplementation. There is significant evidence that suggests that calcium supplementation increases penetration into coronary arteries, particularly in diabetics.1 This can increase the risk of heart disease. Getting calcium slowly through the diet is ideal and has been associated with a reduced risk of colorectal cancer.
Foods rich in calcium:
Consider supplementing with vitamin D if serum levels are low. This study showed a greater reduction in cancer risk among women who had not already been supplementing with vitamin D. This finding suggests that individuals with vitamin D deficiency had the greatest benefit. Analysis of the WHI and VITAL trial showed that vitamin D supplementation, without calcium supplementation was associated with a 13% to 17% reduction in cancer mortality.
Avoid giving calcium supplements with vitamin D. Vitamin D enhances the absorption of calcium, and if high doses of calcium are given at the same time, the body thinks it needs less calcium. This results in the body down-regulating the conversation of sunlight to vitamin D, reducing natural production.
The best advice has been handed down for centuries; enjoy multicolored whole foods and then go out into the sun and play!
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