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High Confidence
Systematic ReviewPMC Full Text2023

Health Effects of Vitamin D supplementation: Lessons Learned from Randomized Controlled Trials and Mendelian Randomization Studies

Bouillon R, et al • J Bone Miner Res

Key Finding

Cancer mortality: daily dosing RR 0.88 (95% CI 0.78-0.98, 10 trials); bolus RR 1.07 (ineffective); VITAL: normal BMI cancer OR 0.76; shift focus to deficient individuals

Key Findings

  • 1Cancer mortality: daily dosing RR 0.88 (12% reduction); bolus ineffective
  • 2Normal BMI subgroup: cancer incidence OR 0.76 (VITAL)
  • 32014 Cochrane all-cause mortality: RR 0.94 (modest benefit)
  • 4Benefits mainly in vitamin D-deficient individuals - shift from universal to targeted supplementation

Original title: “Health Effects of Vitamin D supplementation: Lessons Learned from Randomized Controlled Trials and Mendelian Randomization Studies”

Plain English Summary

Review of large RCTs and MR studies on vitamin D. Daily dosing reduced cancer mortality 12% (RR 0.88); bolus dosing ineffective. Benefits mainly in deficient individuals.

In-Depth Analysis

Study Details

Authors: Roger Bouillon, Meryl S LeBoff, Rachel E Neale
Institutions: KU Leuven, Harvard/Brigham & Women's, QIMR Berghofer
Journal: J Bone Miner Res, 2023 Oct; 38(10):1391-1403
PMCID: PMC10592274

Key Statistics (from original paper)

Cancer Incidence
  • •VITAL and ViDA: No overall reduction
  • •VITAL (normal BMI <25): OR 0.76 (95% CI 0.63-0.90)
Cancer Mortality

Meta-analysis (14 RCTs, 104,727 participants, 2,015 deaths):

  • •Overall: Non-significant 6% reduction
  • •Daily dosing (10 trials): RR 0.88 (95% CI 0.78-0.98) ✓
  • •Bolus dosing (4 trials): RR 1.07 (95% CI 0.91-1.24) ✗

VITAL (excluding first 2 years):

  • •Cancer mortality: OR 0.75 (95% CI 0.59-0.96) ✓
All-Cause Mortality
  • •2014 Cochrane (~75,000 participants): RR 0.94 (95% CI 0.91-0.98)
  • •Recent large RCTs (vitamin D-replete adults): No effect
Key Population Note
  • •Mean baseline 25(OH)D: 22-30.7 ng/mL across major trials
  • •Results don't apply to deficient or institutionalized populations
Principal Conclusion

Shift focus from universal supplementation to targeted approaches in vitamin D-deficient individuals.

Source: PMC full text (PMC10592274)

Paradigm Relevance

How this study applies to different clinical perspectives:

Standard Medical

Relevant

Conventional clinical guidelines used by most doctors

Why it matters:

Key evidence that widespread supplementation of replete populations is not beneficial; supports targeted testing and treatment

Research Consensus

Relevant

Current scientific understanding, often ahead of guidelines

Why it matters:

Clarifies which outcomes have causal support (cancer mortality, autoimmune) vs. confounded associations (CVD, fractures in replete)

Metabolic Optimization

Relevant

Proactive targets for optimal health, not just disease absence

Why it matters:

Important nuance: benefits exist but are concentrated in deficiency; daily dosing superior to bolus; "more is better" not supported

Study Details

Type
Systematic Review
Methodology
Narrative review of large RCTs (VITAL, ViDA) and meta-analyses. Focus on vitamin D-replete populations. Includes Mendelian randomization findings.

Evidence Quality

Review from PMC10592274. KU Leuven, Harvard, QIMR Berghofer authors.

Topic

Vitamin Devidence synthesisrcts

Related Biomarkers

25 OH D

Calculate & Evaluate on Metabolicum

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Vitamin D

Evaluator

Evaluate vitamin D status and optimal levels

Original Source

View on PubMedView DOIFull Text (Open Access)

DOI (Digital Object Identifier) is a permanent link to this publication. Unlike website URLs that can change, a DOI always resolves to the correct source.

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