D-Health Trial Study on Vitamin D3 Supplementation

According to a recent trial, D-Health Trial conducted by Rachel E Neale and colleagues, supplementation of vitamin D3 on a monthly basis to unscreened elderly persons did not lower all-cause death.

The findings of this study were published in The Lancet Diabetes & Endocrinology on 10th January, 2022.

The impact of vitamin D3 supplementation on mortality in unscreened people is unknown. As a result, the purpose of this study was to see if monthly doses of vitamin D3 increased mortality in older Australians.

This was a randomized, double-blind, placebo-controlled trial of oral vitamin D3 supplementation (60,000 IU per month) in Australians aged 60 and above recruited from the Commonwealth electoral roll across the country. Using automated computer-generated permuted block randomization, participants of this trial were randomly assigned (1:1) to receive one oral gel capsule of either 60,000 IU vitamin D3 or placebo once a month for five years.

The research group allocation was concealed from participants, staff, and investigators. The main outcome was all-cause death in all randomly assigned patients. This study also looked at deaths from cancer, cardiovascular disease, and other causes. Using flexible parametric survival models, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated.

Key Points

• Researchers randomly allocated 21,315 individuals between February 14, 2014, and June 17, 2015, with 10,662 assigned to the vitamin D group and 10,653 assigned to the placebo group.
• During follow-up, 4,441 blood samples were taken from randomly chosen individuals (N=3,943), with mean serum 25-hydroxyvitamin D concentrations of 77 (SD 25) nmol/L in the placebo group and 115 (SD 30) nmol/L in the vitamin D group.
• After 5 years of intervention, 1,100 fatalities were observed (placebo 538 [51%]; vitamin D 562 [53%]).
• The primary analysis comprised 10,661 vitamin D group participants and 10,649 placebo group participants. Five individuals were not included because they asked to be removed and their data erased.
• The HR of vitamin D3 impact on all-cause mortality was 1.04 (95% CI 0.93 to 1.18; p=0.47), while the HR of vitamin D3 effect on cardiovascular disease mortality was 0.96 (95% CI 0.72 to 1.28; p=0.77).
• The HR for cancer mortality was 1.15 (95% CI 0.96 to 1.39; p=0.13), while the HR for other causes of death was 0.83 (95% CI 0.65 to 1.07; p=0.15).
• The odds ratio for the per-protocol analysis was OR 1.18 (95% CI 0.00 to 1.40; p=0.06). In exploratory analyses that excluded the first two years of follow-up, individuals randomly allocated to take vitamin D had a numerically greater risk of cancer death than those in the placebo group (HR 1.24 [95% CI 1.01–1.54]; p=0.05).

In conclusion, point estimates and exploratory analysis removing the early follow-up period supported an elevated risk of cancer mortality. In the absence of more information, the cautious principle suggests that this dose regimen may not be suitable in those who are vitamin D deficient.

Reference

Neale, R. E., Baxter, C., Romero, B. D., McLeod, D. S. A., English, D. R., Armstrong, B. K., Ebeling, P. R., Hartel, G., Kimlin, M. G., O'Connell, R., van der Pols, J. C., Venn, A. J., Webb, P. M., Whiteman, D. C., & Waterhouse, M. (2022). The D-Health Trial: a randomised controlled trial of the effect of vitamin D on mortality. In The Lancet Diabetes & Endocrinology. Elsevier BV. https://doi.org/10.1016/s2213-8587(21)00345-4