BACKGROUND AND PURPOSE:

• Previous randomized controlled trials have investigated the impact of vitamin D3 supplementation on a variety of health outcomes, but so far none have examined all-cause mortality as the primary outcome
• Neale et al. (Lancet Diabetes and Endocrinology, 2022) sought to determine whether monthly doses of vitamin D3 influenced mortality in older adults

METHODS:

• Randomized, double-blind, placebo-controlled trial
  • Australian population
• Participants
  • Adults ≥60 years 
• Interventions
  • Vitamin D3 supplementation: 60,000 IU gel cap monthly for 5 years
  • Placebo
• Study design
  • Randomized 1:1
  • Hazard ratios (HRs) and 95% CIs were generated
• Primary outcome
  • All-cause mortality
• Secondary outcomes
  • Mortality from cancer
  • Mortality from cardiovascular disease
  • Mortality from other causes

RESULTS:

• Vitamin D group: 10,662 participants | Placebo: 10,653 participants
  • Median follow-up: 5.7 years (IQR 5.4 to 6.7)
• Mean serum 25-hydroxy-vitamin D concentrations (in blood samples collected from randomly sampled participants)
  • Vitamin D group: 115 (SD 30) nmol/L
  • Placebo group: 77 (SD 25) nmol/L
• Mortality after 5 years of intervention
  • Vitamin D: 5.3% of group
  • Placebo: 5.1% of group
• There was no significant effect of vitamin D3 on
  • All-cause mortality
    • HR 1.04 (95% CI, 0.93 to 1.18); P=0.47
  • Cardiovascular disease mortality
    • HR 0.96 (95% CI, 0.72 to 1.28); P=0.77
  • Cancer mortality
    • HR 1.15 (95% CI, 0.96 to 1.39); P=0.13
  • Mortality from other causes
    • HR 0.83 (95% CI, 0.65 to 1.07); P=0.15
• In exploratory analyses excluding the first 2 years of follow-up, those in the vitamin D group had a higher hazard of cancer mortality than those in the placebo group
  • HR 1.24 (95% CI, 1.01 to 1.54); P=0.05

CONCLUSION:

• Vitamin D3 supplementation in a population of unscreened older adults did not significantly reduce all-cause mortality, or mortality due to other causes
• The authors state

Point estimates and exploratory analyses excluding the early follow-up period were consistent with an increased risk of death from cancer

Pending further evidence, the precautionary principle would suggest that this dosing regimen might not be appropriate in people who are vitamin D-replete

Learn More – Primary Sources:

The D-Health Trial: a randomised controlled trial of the effect of vitamin D on mortality

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