Environmental, personal, and genetic determinants of response to vitamin D supplementation in older adults.
Level 2 - randomized trial
Secondary candidate-gene and determinant analysis of a randomized controlled trial
PubMed 24694335 · doi:10.1210/jc.2013-4101
What was done
In a 12-month pilot randomized controlled trial, 644 adults aged 60 to 84 years were randomly assigned to monthly doses of placebo, 30,000 IU, or 60,000 IU vitamin D3. Baseline personal characteristics were collected via questionnaire, and 88 single-nucleotide polymorphisms (SNPs) in 41 candidate genes were genotyped using Sequenom MassArray. Serum 25-hydroxyvitamin D [25(OH)D] was measured pre- and post-intervention using an immunoassay. Linear regression models examined genetic and nongenetic predictors of change in serum 25(OH)D.
What was found
Supplement dose and baseline 25(OH)D explained 24% of the variability in response to supplementation. Body mass index, self-reported health status, and ambient UV radiation made small additional contributions. SNPs in CYP2R1, IRF4, MC1R, CYP27B1, VDR, TYRP1, MCM6, and HERC2 were initially associated with 25(OH)D change, but only CYP2R1 remained significant after adjustment for multiple testing. Models including SNPs explained a similar proportion of response variability as models with personal and environmental factors (individual effect estimates and exact variance proportions for genetic models were not reported in the abstract).
Why it matters
It shows that while baseline status and dose drive about a quarter of the response to vitamin D supplementation, host genetic variation (notably in CYP2R1) independently contributes to individual response variability.
Limits
Investigation was confined to a candidate panel of 88 SNPs in 41 genes rather than a genome-wide scan. The study tested monthly bolus dosing in an older population (60–84 years), which may not generalize to daily dosing or younger demographics. Specific effect sizes and confidence intervals were omitted from the abstract.
Cited by
- supports Certain genetic polymorphisms cause some individuals to require two to three times the normal dose of vitamin D to raise blood levels to 30 to 40 ng/mL.