The effect of vitamin D supplementation on the gut microbiome in older Australians - Results from analyses of the D-Health Trial.
Level 2 - randomized trial
Randomized, double-blind, placebo-controlled trial
PubMed 37287399 · doi:10.1080/19490976.2023.2221429
What was done
In a substudy of the randomized, double-blind, placebo-controlled D-Health Trial, 835 Australian adults aged 60–84 years (mean age 69.4 years, approximately half women) were assessed after 5 years of monthly supplementation with either 60,000 IU of vitamin D3 (n = 418) or placebo (n = 417). Stool samples collected at approximately 5 years were analyzed with 16S rRNA gene sequencing. Outcomes included alpha diversity indices (Shannon index as primary, richness, inverse Simpson index), beta diversity (Bray-Curtis distance, UniFrac index), the Firmicutes-to-Bacteroidetes ratio, and the relative abundance of the top 20 bacterial genera.
What was found
Vitamin D3 supplementation did not alter gut microbial composition. The primary outcome, Shannon diversity index, was 3.52 in the vitamin D group versus 3.51 in the placebo group (p = 0.50). There were no significant differences in other alpha diversity measures, Firmicutes-to-Bacteroidetes ratio, or the abundance of the top 20 genera, and PERMANOVA showed no distinct clustering in beta diversity between randomization groups.
Why it matters
Observational studies have reported correlations between vitamin D status and microbiome composition, but this trial demonstrates that long-term high-dose vitamin D supplementation does not meaningfully modify gut microbial diversity or taxonomy in generally healthy older adults.
Limits
Stool samples were only collected at 5 years without baseline pre-supplementation samples, precluding analysis of individual-level longitudinal changes. The study evaluated monthly bolus dosing rather than daily administration, used 16S rRNA sequencing rather than higher-resolution metagenomics, and was restricted to older Australian adults.