Vitamin D Supplementation and Cancer Risk Reduction: A Comprehensive Review of Clinical Evidence and Mechanisms (2025)

By Editorial Team

Abstract

Vitamin D deficiency is a global health concern, with accumulating evidence suggesting that vitamin D supplementation may reduce cancer risk and improve cancer mortality. This review synthesizes data from randomized controlled trials, meta-analyses, and umbrella reviews, emphasizing daily supplementation of approximately 2000 IU (50 µg) vitamin D3. The evidence supports a modest but consistent reduction in advanced cancer risk and cancer-specific mortality, particularly with regular dosing rather than intermittent bolus administration. Site-specific cancer prevention effects are most pronounced for colorectal, breast, lung, and renal cell carcinomas. Key challenges include heterogeneity in study designs, dosing regimens, and population characteristics. We discuss mechanistic insights, safety, and future research directions aimed at bridging gaps between observational and clinical trial data.

Vitamin D Supplementation and Cancer Risk Reduction

Keywords

Vitamin D, cancer prevention, supplementation, randomized controlled trials, meta-analysis, umbrella review, cancer mortality, 25-hydroxyvitamin D

Introduction

Vitamin D plays a central role in calcium metabolism and bone health, but its influence extends to several extraskeletal processes, including cell growth regulation, apoptosis, and immune modulation. Epidemiological studies have long suggested inverse correlations between serum vitamin D levels and cancer incidence. However, the translation of preclinical and observational data into clinical recommendations has been hindered by inconsistent trial outcomes and diverse supplementation protocols.

Recent large-scale RCTs and systematic umbrella reviews have clarified vitamin D’s impact, highlighting its potential in reducing advanced cancer risk and mortality and preventing specific cancer types. This review integrates these findings to inform clinical and public health guidelines applying vitamin D supplementation in cancer prevention.

Methods

A narrative synthesis of recent high-quality RCTs, systematic reviews, meta-analyses, and umbrella reviews was performed. Focus was placed on studies assessing vitamin D supplementation’s effect on total cancer incidence, site-specific cancers, cancer progression, and mortality. Key databases searched included PubMed, Cochrane Library, and MEDLINE, encompassing studies published up to 2025.

Results

Recommended Dosage and Serum Levels

Pludowski et al. (2024) recommend a daily supplementation dose of 2000 IU vitamin D3 to achieve and maintain protective serum 25(OH)D concentrations (>50 nmol/L in >99% of adults), with strong evidence supporting safety and efficacy over long-term use .

Cancer Mortality and Advanced Cancer Risk

Kuznia et al. (2023) performed a meta-analysis of 14 RCTs (n=104,727), indicating a non-significant overall 6% cancer mortality reduction with vitamin D supplementation, but a 12% significant reduction with daily dosing regimens, especially among older adults (≥70 years) . The 2020 VITAL trial demonstrated a 17% reduction in advanced cancer incidence in vitamin D-supplemented groups, particularly in healthy-weight individuals .

Site-Specific Cancer Prevention

Schömann-Finck et al. (2025) summarized observational and clinical data suggesting preventive effects of vitamin D intake on breast, colorectal, and lung cancers, with colorectal cancer mortality reduction most consistently observed. Evidence for pancreatic and prostate cancer remains inconclusive due to methodological heterogeneity . Petrelli et al. (2024) reinforced these findings, providing strong evidence for vitamin D3’s role in lowering risks of head and neck, breast, colorectal, lung, renal cell, and thyroid cancers .

Mechanistic Insights and Moderators

Vitamin D modulates critical pathways, including cell cycle control, apoptosis, and immune function, inhibiting tumor growth and metastasis. Chronic inflammation associated with obesity may impair vitamin D’s anti-cancer effects, explaining variable efficacy based on BMI.

Discussion

The totality of evidence indicates that vitamin D supplementation, particularly daily dosing regimens of around 2000 IU, safely reduces advanced cancer risk and cancer mortality while contributing to the prevention of several site-specific cancers. Despite promising results, heterogeneity in trial design, dosing protocols, and participant characteristics warrants cautious interpretation.

Bridging the translational gap between observational studies and RCTs remains essential. Future trials should emphasize standardized dosing, stratification by baseline vitamin D status and BMI, and possibly employ innovative virtual trial designs to enhance reach and feasibility.

Public health policies should advocate for routine screening for vitamin D deficiency and supplementation in deficient populations as a cost-effective adjunct for cancer prevention.

Conclusion

Vitamin D supplementation shows a consistent association with modest reductions in cancer mortality and incidence of certain cancers. Given its affordability, safety, and other health benefits, daily supplementation with 2000 IU vitamin D3 represents a practical preventive strategy pending further research to define optimal individualized protocols.

References

  • Pludowski P, Grant WB, Karras SN, et al. Vitamin D Supplementation: A Review of the Evidence Arguing for a Daily Dose of 2000 International Units (50 µg) of Vitamin D for Adults in the General Population. Nutrients. 2024;16(3):391. doi:10.3390/nu16030391

  • Kuznia S, Zhu A, Akutsu T, et al. Efficacy of vitamin D3 supplementation on cancer mortality: Systematic review and individual patient data meta-analysis of randomized controlled trials. Ageing Res Rev. 2023;87:101923. doi:10.1016/j.arr.2023.101923

  • Chandler PD, Chen WY, Ajala ON, et al. Effect of Vitamin D3 Supplements on Development of Advanced Cancer: A Secondary Analysis of the VITAL Randomized Clinical Trial. JAMA Netw Open. 2020;3(11):e2025850. doi:10.1001/jamanetworkopen.2020.25850

  • Schömann-Finck M, Vogt T, Reichrath J. Umbrella Review on the Relationship Between Vitamin D Intake and Cancer. Anticancer Res. 2025;45(3):855-864. doi:10.21873/anticanres.17474

  • Petrelli F, Deda R, Borgonovo K, et al. Vitamin D3 and cancer risk in healthy subjects: An umbrella review of systematic review and meta-analysis. Clin Nutr ESPEN. 2024;63:776-786. doi:10.1016/j.clnesp.2024.08.014

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