Vitamin D Intake, Serum 25-Hydroxyvitamin-D (25(OH)D) Levels, and Cancer Risk: A Comprehensive Meta-Meta-Analysis Including Meta-Analyses of Randomized Controlled Trials and Observational Epidemiological Studies.
Level 1 - systematic review of randomized trials
Systematic meta-meta-analysis pooling existing meta-analyses of randomized controlled trials and observational studies
PubMed 37375626 · doi:10.3390/nu15122722
What was done
The authors conducted a meta-meta-analysis across PubMed/Medline, Web of Science, and Scopus to evaluate the associations between vitamin D intake, serum 25-hydroxyvitamin-D (25(OH)D) concentrations, and cancer incidence and mortality. They combined effect estimates (odds ratios, risk ratios, and hazard ratios) across 35 eligible meta-analyses comprising 59 reports spanning both randomized controlled trials (RCTs) and observational epidemiological studies.
What was found
In overall pooled analyses, higher vitamin D intake and higher serum 25(OH)D levels were associated with lower cancer risk (OR = 0.93, 95% CI: 0.90–0.96, p < 0.001; OR = 0.80, 95% CI: 0.72–0.89, p < 0.001, respectively) and reduced cancer-related mortality (RR = 0.89, 95% CI: 0.86–0.93, p < 0.001; RR = 0.67, 95% CI: 0.58–0.78, p < 0.001, respectively). However, when restricting the analysis to meta-analyses composed exclusively of RCTs, vitamin D intake showed no significant association with cancer risk (OR = 0.99, 95% CI: 0.97–1.01, p = 0.320). Subgroup analyses found significant reductions in incidence for colorectal cancer (OR = 0.89, 95% CI: 0.83–0.96, p = 0.002) and lung cancer (OR = 0.88, 95% CI: 0.83–0.94, p < 0.001).
Why it matters
This umbrella review synthesizes extensive literature but underscores a critical disconnect: the protective associations observed between vitamin D and overall cancer incidence in epidemiological studies disappear when evaluated in randomized controlled trials.
Limits
The analysis synthesizes secondary meta-analytic estimates and pools different statistical metrics (ORs, RRs, and HRs), risking aggregation bias and study overlap across included reviews. Specific supplementation dosages, baseline vitamin D deficiencies, and duration of exposure were not detailed in the abstract, and observational links remain susceptible to confounding and reverse causality.
Cited by
- supports Having serum vitamin D levels above 30 ng/mL is associated with lower all-cause mortality, particularly lower cancer mortality and respiratory disease mortality.