Long-term calcium and vitamin D supplementation does not impact all-cause mortality

1. In this randomized controlled trial, long-term calcium and vitamin D (CaD) supplementation was associated with lower cancer mortality and higher cardiovascular mortality among postmenopausal women compared to placebo.

2. Overall, long-term CaD supplementation did not impact all-cause mortality in postmenopausal women. 

Evidence Rating Level: 1 (Excellent)

Study Rundown: Adequate calcium and vitamin D intake is important in maintaining health and preventing conditions such as cancers and cardiovascular disease, especially in older adults. The role of supplementation, however, is unclear. The randomized placebo-controlled Women’s Health Initiative CaD trial was conducted to study the effects of daily CaD supplementation in postmenopausal women over a seven years period. The current study was a 20-year long-term follow-up to assess health events and mortality of the study participants post-intervention. With a median follow-up of 22.3 years, it was found that women randomized to receive CaD supplements had a lower risk of cancer mortality and an increased risk of mortality from cardiovascular disease (CVD) compared to those in the placebo group. When stratified by supplement use prior to the study, CaD group assignment demonstrated reductions in cancer risk among those without previous supplementation compared to placebo. Overall, the study intervention did not impact all-cause mortality. The study was limited in that outcomes regarding hip fractures, and CVD incidence was only available for a subset of participants, along with demographic limitations in the original sample.

Click here to read the study in AIM

In-Depth [randomized controlled trial]: The current study was a long-term post-hoc analysis of a seven-year multi-center randomized placebo-controlled trial by the Women’s Health Initiative to investigate the health impact of CaD supplementation in postmenopausal women. In the original trial, 36,282 postmenopausal women were randomized 1:1 to receive daily supplementation of 400mg of elemental calcium equivalent and 400IU of vitamin D (CaD) daily or placebo for seven years. Before the trial, 11,106 participants reported no prior supplement use, and 24,651 reported prior use. The current study, the incidence rates of colorectal, invasive breast, and total cancer; hip fractures and CVD events (including myocardial infarction, coronary death, stroke, congestive heart failure, and other cardiovascular deaths); disease-specific and all-cause mortality. Over a median cumulative follow-up period of 22.3 years, the CaD group (1,817 deaths) had a 7% reduction in cancer mortality risk compared to the placebo group (1,943 deaths) (hazard ratio [HR], 0.93; 95% Confidence Interval [CI], 0.87-0.99). Conversely, the CaD group (2,621 deaths) saw a 6% increase in CVD-related mortality compared to placebo (2,420 deaths; HR, 1.06; 95% CI, 1.01-1.12). When stratified by pre-randomization supplement use, CaD group assignment was associated with reductions in the risks of colorectal cancer (HR, 0.69; 95% CI, 0.54-0.87), invasive breast cancer (HR, 0.81; 95% CI, 0.71-0.94), and total cancer (HR, 0.89; 95% CI, 0.82-0.96) compared to placebo among those who were not taking supplements before. Overall, there was no significant effect associated with CaD group assignment on all-cause mortality (HR, 1.00; 95% CI, 0.97-1.03), nor was there an impact on the incidence of hip fractures and total CVD events. These results showed that CaD supplementation during the original seven-year trial did not significantly impact all-cause mortality in postmenopausal women.

Image: PD

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