A Randomized Double-Blind Placebo-Controlled Trial of the Effect of Vitamin D3 Supplementation on Breast Density in Premenopausal Women

Background: This double-blind, placebo-controlled parallel group trial assessed whether oral supplementation with 1,000, 2,000, or 3,000 IU/day vitamin D3 over one year reduces percent mammographic breast density in premenopausal women. Methods: The trial was conducted between October 2012 and June 2015, among premenopausal female volunteers from Quebec City (Quebec, Canada). Women were randomized with ratio 1:1:1:1 to one of four study arms (1,000, 2,000, or 3,000 IU/day vitamin D3 or placebo). The primary outcome was mean change in percent mammographic breast density. Participants and research team were blinded to study arm assignment. Results: Participants (n = 405) were randomized to receive 1,000 (n = 101), 2,000 (n = 104), or 3,000 IU/day (n = 101) vitamin D3, or a placebo (n = 99). The primary analysis included 391 participants (96, 99, 100, and 96, respectively). After the one-year intervention, mean ± SE change in percent breast density in the arms 1,000 IU/day (–5.5% ± 0.5%) and 2,000 IU/day (–5.9% ± 0.5%) vitamin D3 was similar to that in the placebo arm (−5.7% ± 0.5%) (P values = 1.0). In the 3,000 IU/day vitamin D3 arm, percent breast density also declined but slightly less (–3.8% ± 0.5%) compared with placebo arm (P = 0.03). Adherence to intervention was excellent (92.8%), and reporting of health problems was comparable among study arms (P ≥ 0.95). All participants had normal serum calcium. Conclusions: In premenopausal women, one-year supplementation with 1,000, 2,000, or 3,000 IU/day vitamin D3 resulted in a reduction of percent breast density no greater than that seen with the placebo. Impact: At doses of 1,000–3,000 IU/day, vitamin D supplementation will not reduce breast cancer risk through changes in breast density. Cancer Epidemiol Biomarkers Prev; 26(8); 1233–41. ©2017 AACR.