Decades-Long Study Reveals Surprising Effects of Vitamin D and Calcium on Women's Health: Cancer Mortality Down, Heart Risk Up

The study titled "Long-Term Effect of Randomization to Calcium and Vitamin D Supplementation on Health in Older Women" presents the findings from a post-hoc analysis of data collected during the Women’s Health Initiative Calcium and Vitamin D (WHI CaD) supplementation trial. The original trial was a large-scale, randomized controlled trial designed to test the effects of daily calcium and vitamin D supplements on health outcomes in postmenopausal women.

Researchers analyzed the long-term health outcomes of 36,282 postmenopausal women who had been randomly assigned to receive either 1000 mg of calcium carbonate with 400 IU of vitamin D3 daily or a placebo, over a median intervention period of 7 years. The participants were enrolled across 40 trial sites in the United States, and neither a history of breast cancer nor colorectal cancer was reported among them at the start of the trial. The study allowed women to continue their personal use of calcium and vitamin D supplements, if applicable, alongside the trial supplements.

The primary health outcomes measured were the incidence of invasive breast cancer, colorectal cancer, total cancer, disease-specific and all-cause mortality, total cardiovascular disease (CVD), and hip fractures. The outcomes were stratified by the women’s personal supplement use prior to randomization to assess whether previous supplement intake influenced the effectiveness of the CaD intervention.

After more than 20 years of follow-up, the study found that postmenopausal women assigned to the CaD supplements saw a slight but significant 7% reduction in cancer mortality (with 1817 deaths in the CaD group versus 1943 deaths in the placebo group) when compared to those on the placebo. However, there was also a 6% increase in CVD mortality in the CaD group (2621 deaths versus 2420 deaths in the placebo group). No significant effect was detected on all-cause mortality, which remained statistically unchanged between the two groups.

When taking personal supplementation history into account, the estimates for cancer incidence varied widely, suggesting that prior supplement use may have an impact on cancer risk. However, prior supplement use did not seem to alter the effects on mortality rates, except for CVD mortality.

One limitation of the study was that the specific effects of calcium versus vitamin D, or their combined supplementation, could not be disentangled. Additionally, outcomes for hip fracture and CVD were available only for a subset of the participants, which may limit the generalizability of the findings.

In conclusion, long-term follow-up of the WHI CaD trial indicates that calcium and vitamin D supplements may modestly reduce cancer mortality and slightly increase CVD mortality among postmenopausal women, without affecting the overall risk of death. These findings highlight the complex role of nutrient supplementation in long-term health and the importance of personalized health strategies when considering supplement use.

The study was funded primarily by the National Heart, Lung, and Blood Institute of the National Institutes of Health and was published in the Annals of Internal Medicine on March 12, 2024.