A Randomized Double-Blind Placebo-Controlled Trial of the Effect of Vitamin D 3 Supplementation on Breast Density in Premenopausal Women

This double-blind, placebo-controlled parallel group trial assessed whether oral supplementation with 1,000, 2,000, or 3,000 IU/day vitamin D over one year reduces percent mammographic breast density in premenopausal women. 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 D or placebo). The primary outcome was mean change in percent mammographic breast density. Participants and research team were blinded to study arm assignment. Participants ( = 405) were randomized to receive 1,000 ( = 101), 2,000 ( = 104), or 3,000 IU/day ( = 101) vitamin D , or a placebo ( = 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 D was similar to that in the placebo arm (-5.7% ± 0.5%) ( values = 1.0). In the 3,000 IU/day vitamin D arm, percent breast density also declined but slightly less (-3.8% ± 0.5%) compared with placebo arm ( = 0.03). Adherence to intervention was excellent (92.8%), and reporting of health problems was comparable among study arms ( ≥ 0.95). All participants had normal serum calcium. In premenopausal women, one-year supplementation with 1,000, 2,000, or 3,000 IU/day vitamin D resulted in a reduction of percent breast density no greater than that seen with the placebo. At doses of 1,000-3,000 IU/day, vitamin D supplementation will not reduce breast cancer risk through changes in breast density. .