Large Individual Differences in Serum 25-HydroxyVitamin D Response to Vitamin D Supplementation: Effects of Genetic Factors, Body Mass Index, and Baseline ConcentrationResults from a Randomized Controlled Trial

Abstract

The main aim of the study was to determine the influence of genetic factors on the serum 25-hydroxyVitamin D response to Vitamin D supplementation. The main outcome measure was an increase in serum 25-hydroxyVitamin D after Vitamin D supplementation. The patients are part of a randomized controlled trial in individuals with prediabetes assigned to 20 000 IU of Vitamin D3 per week or placebo for 12 months. A total of 484 subjects were included in the analyses and genotyped for single nucleotide polymorphisms in the DBP, DHCR7, CYP2R1, and CYP24A1 genes. Single nucleotide polymorphisms from all 4 selected genes were significantly related to baseline serum 25-hydroxyVitamin D concentrations with differences between major and minor homozygote genotypes ranging from 4.4 to 19.2 nmol/l. In the subjects given Vitamin D, those with genotypes with the highest baseline 25-hydroxyVitamin D concentration also had the highest 25-hydroxyVitamin D concentration after 12 months, and the increase (delta) in 25-hydroxyVitamin D was significantly related to 3 of the single nucleotide polymorphisms. The increase in serum 25-hydroxyVitamin D was also higher in lean vs. obese subjects, and higher in those with low baseline 25-hydroxyVitamin D concentrations. When combining these 3 factors in a linear regression model, the predicted (and observed) difference in 25-hydroxyVitamin D increase between high and low responders to the supplementation was approximately 60 nmol/l. In conclusion, due to genetic, body mass, and baseline 25-hydroxyVitamin D differences, there are huge individual variations in the serum 25-hydroxyVitamin D response to Vitamin D supplementation that could be of clinical importance.