Vitamin D, calcium supplementation in older women shows mixed long-term results

Key takeaways:

• Calcium and vitamin D supplements appeared to reduce cancer mortality after more than 20 years of follow-up.
• However, the supplements also appeared to raise the risk for CVD mortality in the long-term as well.

Calcium and vitamin D supplementation decreased cancer mortality among postmenopausal women after more than 2 decades of follow-up but increased CVD mortality, researchers found.

Cynthia A. Thomson, PhD, RD, a professor at the University of Arizona College of Public Health, and colleagues conducted a post-hoc analysis of the Women’s Health Initiative (WHI) multicenter randomized controlled trial, which assigned participants to either daily placebo or calcium and vitamin D (CaD) supplementation — consisting of 1,000 mg of calcium carbonate and 400 IU of vitamin D3 — for 7 years.

“The 20-year adjudication of health events and mortality” in the trial, “complemented with National Death Index data, afforded an opportunity to evaluate longer-term health risks, especially for cancer and mortality in WHI,” they wrote in the Annals of Internal Medicine.

The researchers measured the impact of CaD on several health outcomes, including the incidences of colorectal, invasive breast and total cancer, as well as disease-specific, all-cause and CVD mortality and hip fractures.

The study cohort comprised 36,282 postmenopausal women who had no history of breast or colorectal cancer.

The researchers found a 7% (HR = 0.93; 95% CI, 0.87-0.99) reduction in cancer mortality and a 6% (HR = 1.06; 95% CI, 1.01-1.12) increase in CVD mortality among women assigned to CaD vs. placebo after a median cumulative follow-up of 22.3 years. CaD had no significant effects on other measures, including all-cause mortality and hip fractures, they said.

Thomson and colleagues found that estimates for cancer incidence varied widely based on whether participants reported supplement use before randomization; among participants without prior CaD use, there were 11%, 31% and 19% lower incidences of total, colorectal and invasive breast cancer, respectively.

“In contrast, point estimates for those reporting prior use exceeded 1, although 95% CIs were compatible with a negligible reduction to a modest increase in risk,” they wrote.

Thomson and colleagues explained that because of multiple comparisons made in the study, “our results should be interpreted with caution,” although “if real, the 7% reduction in longer-term cancer mortality would be clinically meaningful and is consistent with an earlier report of intervention phase outcomes.”

They also explained why CaD may reduce cancer incidence, “including decreases in tumor invasiveness and angiogenesis; specific effects on bile acid, fatty acid metabolism, and gut uptake; and increased expression of protein kinase C.”

The research had some limitations, Thompson and colleagues said. For example, the study had limited follow-up data on total CVD and hip fractures, and the findings may not be generalizable due to the sample being mainly composed of non-Hispanic white women.

Also, “given the study design, we could not disentangle the added benefit or harms of supplementation with CaD in combination versus vitamin D alone, a topic worthy of future study,” the researchers concluded.