The Moderate certainty evidence presented in this meta-analysis underscores the profound impact of circulating 25-hydroxyvitamin D [25(OH)D] levels on cancer patient outcomes. Although this analysis is limited to colorectal cancer, breast cancer, and lymphoma, there’s no reason to believe it doesn’t apply across the board.

Yes it is based on observational studies and not Randomized Controlled Trials (RCTs), but the consistent association is too compelling to ignore: a higher 25(OH)D level is significantly associated with better overall survival and reduced cancer-specific mortality. Specifically, a 10-nmol/L increment in 25(OH)D being linked to a 4% reduction in deaths.

The current evidence suggests that clinicians should target levels in the high-normal, optimal range—not just for prevention, but as a crucial, low-risk, and cost-effective adjuvant strategy for improving treatment outcomes and long-term survival for patients with these specific cancers.

🎯 Clinical Bottom Line

This meta-analysis provides Moderate certainty evidence that higher circulating 25-hydroxyvitamin D [25(OH)D] levels (measured at or near the time of diagnosis and before treatment) are significantly associated with better clinical outcomes (improved overall survival, reduced cancer-specific mortality, and better disease-free survival) for patients with colorectal cancer, breast cancer, and lymphoma.

A 10-nmol/L increment in circulating 25(OH)D was associated with a 4% reduction in deaths from all causes among cancer patients, suggesting a non-linear dose-response relationship.

Caution: This finding is based on observational studies, meaning a causal relationship cannot be proven and requires validation through large-scale Randomized Controlled Trials (RCTs).

Summary of Key Results

The meta-analysis included 25 studies with 17,332 cases and used the Hazard Ratio (HR), where an HR less than 1.0 indicates a reduced risk for the group with higher 25(OH)D.

• Overall Survival (OS): Patients in the highest quartile of circulating 25(OH)D had significantly improved OS.

  • Colorectal Cancer: Pooled HR = 0.55 (95% CI: 0.33–0.91), indicating a 45% lower risk of death from any cause.

  • Breast Cancer: Pooled HR = 0.63 (95% CI: 0.51–0.77), indicating a 37% reduced risk of death from all causes.

  • Lymphoma: Pooled HR = 0.48 (95% CI: 0.36–0.64), indicating a 52% lower risk of death from all causes.

• Cancer-Specific Mortality (CSM): Higher 25(OH)D levels were significantly associated with a reduced risk of death specifically from the cancer.

  • Colorectal Cancer: Reduced risk by 35% (Pooled HR = 0.65).

  • Lymphoma: Reduced risk (Pooled HR = 0.50).

• Disease-Free Survival (DFS): Higher 25(OH)D levels were associated with improved DFS (the time a patient remains free of disease after treatment).

  • Breast Cancer: Improved DFS (Pooled HR = 0.42).

  • Lymphoma: Improved DFS (Pooled HR = 0.80).

• Dose-Response: A 10 nmol/L increment in circulating 25(OH)D level was associated with an overall survival HR of 0.96 (95% CI: 0.95–0.97) for all cancer patients, suggesting a 4% reduction in the risk of all-cause death.

Assertive Critical Appraisal

Certainty of Evidence (GRADE Framework)

The overall certainty of evidence is Moderate because it comes from observational cohort studies, which carry an inherent risk of confounding bias (unmeasured variables like healthier lifestyle contributing to better outcomes). The causal relationship cannot be proven without RCTs.

Heterogeneity (Consistency of Results)

The I2 statistic quantifies heterogeneity:

• Colorectal Cancer Overall Survival: Significant heterogeneity was found (I2 = 89%). An I2 of 89% indicates substantial heterogeneity, meaning the pooled average (HR = 0.55) should be interpreted with significant caution.

• Breast Cancer and Lymphoma: Low heterogeneity was reported for the key outcomes in breast cancer (P for heterogeneity = 0.32) and lymphoma, strengthening the pooled results for these specific cancer types.

Publication Bias

The authors found no significant publication bias for colorectal cancer outcomes or breast cancer outcomes using Egger’s linear test and funnel plots. This is a strength of the review, as publication bias can lead to an overestimation of effects.

Research Design and Data

• Study Design: Systematic Review and Meta-Analysis of cohort studies.

• Objective: To assess the associations of circulating 25(OH)D levels measured at or near the time of diagnosis and outcomes for cancer patients.

• Included Studies: 25 studies with a total of 17,332 cancer patients covering colorectal, breast, prostate, lung, and other cancer types.

• Search Strategy: Searches were performed in the PubMed and MEDLINE databases, updated to December 2013.

Bibliographic Data

Title: Review: The Impacts of Circulating 25-Hydroxyvitamin D Levels on Cancer Patient Outcomes: A Systematic Review and Meta-Analysis

Authors: Mian Li, Peizhan Chen, Jingquan Li, Ruiai Chu, Dong Xie, and Hui Wang

Journal: J Clin Endocrinol Metab

Year: 2014

DOI: 10.1210/jc.2013-4320

Mandatory Disclaimer: This AI-generated analysis is for informational and research purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of a qualified health provider with any questions you may have regarding a medical condition.