Effect of Vitamin D Supplementation on Risk of Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
What this study found
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…
- Study & population
- 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…
- Key limitation
- 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…
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Open PDFOriginal 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 clarify the efficacy of vitamin D supplementation on risk of breast cancer. Methods: MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and abstracts of three major conferences were searched (up to December 8, 2020). Parallel randomized controlled trials (RCTs) examining the efficacy of vitamin D supplementation on risk of breast cancer or change of mammography compared with placebo in females were included. Data were meta-analyzed using a random-effects model. Bayesian meta-analysis was conducted to synthesize the results using data from observational studies as priors. Results: Seven RCTs were identified for effect of vitamin D on risk of breast cancer, with 19,137 females included for meta-analysis. No statistically significant effect of vitamin D on risk of breast cancer was found in classical random-effects meta-analysis (risk ratio = 1.04, 95% confidence interval: 0.84–1.28, p = 0.71). When Bayesian meta-analyses were conducted, results remained non-significant. There was no statistically significant effect of vitamin D on mammography density observed: mean difference = 0.46, 95% confidence interval: −2.06 to 2.98, p = 0.72. Conclusion: There is insufficient evidence to support the efficacy of vitamin D supplementation in breast cancer risk and change of mammography density. The protective effect of vitamin D on risk of breast cancer from previous observational studies may be overestimated. Systematic Review Registration: PROSPERO, identifier CRD42019138718.