Effect of Vitamin D Supplementation on Risk of Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Frontiers in Nutrition
Q1
Apr 2021
Citations:25
Influential Citations:0
Systematic Reviews / Meta-Analyses
86
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Methods
Parallel randomized controlled trials enrolling adult female participants (≥18 years) from North America and Europe; included premenopausal and postmenopausal women; comparisons against placebo; some trials allowed cointerventions such as calcium or omega-3 fatty acids.
Intervention
Vitamin D3 (cholecalciferol) supplementation regimens varied across trials: daily doses from 400 to 3,000 IU/day (examples include 800, 1,100, 2,000, and 3,000 IU/day); intermittent high-dose regimens included 100,000 IU every 3 months and 200,000 IU loading followed by 100,000 IU monthly; some arms combined vitamin D with calcium (1,400–1,500 mg/day) or omega-3 fatty acids; all regimens were oral; follow-up durations ranged from 4 months to about 5.3 years.
Results
Vitamin D3 supplementation did not significantly reduce breast cancer risk or affect mammographic density. Across 7 RCTs (19,137 women), the pooled risk ratio for breast cancer was 1.04 (95% CI 0.84–1.28; P = 0.71). For mammographic density, data from 3 trials (584 participants) showed no significant change (mean difference 0.46; 95% CI −2.06 to 2.98; P = 0.72). Bayesian analyses remained non-significant across prior assumptions. There is insufficient evidence to support the efficacy of vitamin D supplementation for breast cancer risk reduction or mammographic density changes; observational studies suggesting protection may be overestimated; more high-quality RCTs with higher doses and longer follow-up are needed.
Limitations
Some trials had risk of bias (incomplete outcomes, loss to follow-up); several studies had short follow-up (<12 months); substantial heterogeneity for mammographic density; results dominated by two large trials; trials conducted in developed countries only; limited data on cancer subtypes and long-term safety at higher doses.

Abstract

Objective: Laboratory findings indicated that vitamin D might have a potent protective effect on breast cancer, but epidemiology studies reported conflicting results. The aim of the study was to conduct a systematic review and meta-analysis to clarif...