Some doctors may be scratching their heads over a new analysis reporting that combined calcium and vitamin D (CaD) supplements appear to be associated with a slight 6% increase in cardiovascular (CVD) mortality, a slight 7% decrease in cancer risk, and no effect on osteoporotic fracture in postmenopausal women.
The study, in Annals of Internal Medicine, found no effect of supplementation on all-cause mortality.
The findings emerged from an analysis of more than 20 years’ follow-up data on a randomized trial in postmenopausal women conducted as part of the Women’s Health Initiative (WHI).
Cynthia A. Thomson, PhD, RD, first author and cancer prevention scientist at the Arizona Cancer Center and a professor of health promotion sciences at the University of Arizona in Tucson said the findings recommend individualized assessment of the need for supplements for older women as they consider them in hopes of preventing fractures.
Arizona Cancer Center
Dr. Cynthia A. Thomson
“Evaluate your patients individually and understand that there are some who may benefit from supplementation, for example, in terms of reducing colorectal cancer mortality,” Dr. Thomson said in an interview. The approach should be nuanced. “If you check the adequacy of vitamin D and calcium in their diets, supplementation may not be needed.” She added that supplementation is best considered in the context of a woman’s overall health profile, including risk factors for fracture, heart disease, and cancer, especially colorectal cancer (CRC).
Study Details
The investigators conducted postintervention follow-up of the WHI’s 7-year multicenter randomized intervention trial of CaD vs placebo.
Since existing evidence of long-term health outcomes was limited, the trial, begun in 1999 and closed in 2005, enrolled 36,282 postmenopausal women (mean age 62) with no history of breast or colorectal cancer. They were randomly assigned 1:1 to supplementation with 1000 mg of calcium carbonate (400 mg elemental calcium) plus 400 IU of vitamin D3 daily or placebo, taken twice daily in half doses.
Study outcomes were incidence of CRC, total and invasive breast cancer; disease-specific and all-cause mortality; total CVD; and hip fracture measured through December 2020, with analyses stratified by personal supplement usage.
Cancer. CaD was associated with reduced incident total cancer, CRC, and invasive breast cancer — notably among participants not taking CaD before randomization. Cancer incidence estimates varied widely, the authors noted, when stratified by supplement use before randomization. Noting that CaD seemed to have more cancer-related impact in those without prior supplementation, the authors suggested supplementation may affect cancer biology primarily by augmenting nutrient insufficiency.
An estimated 7% reduction in cancer mortality was observed after a median cumulative follow-up of 22.3 years: 1817 vs 1943 deaths (hazard ratio, 0.93; 95% CI, 0.87-0.99).
CVD. An estimated 6% increase in CVD mortality was seen in the CaD group: 2621 vs 2420 deaths (HR, 1.06; 95% CI, 1.01-1.12). Pretrial supplement users were found to be at higher CVD risk.
Hip fracture. No effect on hip fracture risk was measured, but the authors cautioned that hip fracture and CVD outcomes were available only for a subset of participants, and the effects of calcium alone vs vitamin D alone vs the combination could not be disentangled.
In a small subgroup analysis, some CaD users were seen to respond in terms of bone mineral density but since only 4 of the study’s 40 sites collected such information, the study was underpowered to examine the effect. ”Many other studies, however, show a response to supplementation in women who already have bone mineral deficits,” Dr. Thomson said.