1. MeIn this randomized controlled trial, long-term calcium and vitamin D (CaD) supplementation was associated with reduced cancer mortality and increased cardiovascular disease mortality in postmenopausal women compared with placebo.
2. Overall, long-term CaD supplementation did not affect all-cause mortality in postmenopausal women..
Level of evidence: 1 (Excellent)
Research Summary: Adequate calcium and vitamin D intake is important for maintaining health and preventing conditions such as cancer and cardiovascular disease, especially in older adults. However, the role of supplements is unclear. The randomized, placebo-controlled Women’s Health Initiative CaD trial was conducted to study the effects of daily CaD supplements in postmenopausal women over a 7-year period. The current study was a 20-year long-term follow-up to evaluate health events and mortality in study participants after the intervention. With a median follow-up of 22.3 years, women randomly assigned to receive CaD supplements were found to have a lower risk of death from cancer and a higher risk of death from cardiovascular disease (CVD) compared with the placebo group. When stratified by prestudy supplement use, CaD group assignment showed a reduced cancer risk in those who had never taken supplements before compared with placebo. Overall, the study intervention had no effect on all-cause mortality. The study was limited in that results on hip fracture and incident CVD were only available for a subset of participants, as well as demographic limitations of the original sample.
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detail [randomized controlled trial]: The current study is a long-term post-hoc analysis of a 7-year, multicenter, randomized, placebo-controlled trial conducted by the Women’s Health Initiative to investigate the health effects of CaD supplementation in postmenopausal women. In the original trial, 36,282 postmenopausal women were randomized 1:1 to receive a daily supplement of 400 mg elemental calcium equivalent and 400 IU vitamin D (CaD) or a placebo for 7 years. Prior to the trial, 11,106 participants reported no previous supplement use and 24,651 reported previous use. The current study examined incidence of colorectal cancer, invasive breast cancer, total cancer, hip fracture and CVD events (including myocardial infarction, death from coronary artery disease, stroke, congestive heart failure, and death from other cardiovascular diseases), disease-specific mortality, and all-cause mortality.Over a median cumulative follow-up period of 22.3 years, the CaD group (1,817 deaths) had a 7% reduced risk of cancer death compared with the placebo group (1,943 deaths) (hazard ratio[HR]0.0111). [HR]0.93; 95% CI [CI], 0.87-0.99). Conversely, there was a 6% increase in CVD-related mortality in the CaD group (2621 deaths) compared with placebo (2420 deaths; HR, 1.06; 95% CI, 1.01-1.12). When stratified by prerandomization supplement use, CaD group assignment reduced the risk 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) in those who had not previously taken supplements compared with placebo. Overall, CaD group assignment did not significantly affect all-cause mortality (HR, 1.00; 95% CI, 0.97-1.03), nor did it affect the incidence of hip fracture or all CVD events. These results indicate that CaD supplementation during the first 7 years of the study did not significantly affect all-cause mortality in postmenopausal women.
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