Vitamin D deficiency affects between 31% and 82% of the U.S. population, depending on race/ethnicity, and is associated with hypertension, as well as other cardiovascular outcomes. Several randomized clinical trials of the efficacy of vitamin D supplementation in reducing blood pressure have been conducted with mixed results. These inconsistent clinical trial findings may be explained by the substantial inter-individual variabiliy in the ability of a given vitamin D dose to raise circulating 25-hydroxyvitamin D [25(OH)D] concentrations and, thus, to influence vitamin D-related outcomes. This variability is influenced by genetic variants. However, these variants have not been used to guide the dose of vitamin D supplementation. Our long-term goal is to use Genotype-gUIded vitamin D supplEmentation (GUIDE) to improve vitamin D-related health outcomes. The objective of this application is to conduct a randomized, double-blind, placebo-controlled clinical trial of daily oral vitamin D3 for three months in 558 healthy participants between the ages of 30 and 70 from an existing population-based study. The vitamin D3 dose will be determined by the number of risk alleles in two vitamin D- related genes.
The specific aims are to determine the efficacy of GUIDE in 1) achieving 25(OH)D concentrations of 20-50 ng/mL and 2) lowering blood pressure.
The rationale for the proposed research is that the current vitamin D recommendations and clinical trials take a 'one size fits all' approach, but responses to vitamin D supplementation do not follow this pattern. Applying a pharmacogenomic approach to vitamin D supplementation could be extremely beneficial. Since pharmacogenomic panels are being developed and used in clinical laboratories to aid in clinical decision- making, this is an opportune time to consider the efficacy of genotype-guided vitamin D supplementation.
| Hong, Jaeyoung; Hatchell, Kathryn E; Bradfield, Jonathan P et al. (2018) Transethnic Evaluation Identifies Low-Frequency Loci Associated With 25-Hydroxyvitamin D Concentrations. J Clin Endocrinol Metab 103:1380-1392 |
