Effects of Genetic and Nongenetic Factors on Total and Bioavailable 25(OH)D Responses to Vitamin D Supplementation

J Clin Endocrinol Metab. 2017 Jan 1;102(1):100-110. doi: 10.1210/jc.2016-2930.

Abstract

Context: Little is known about how genetic and nongenetic factors modify responses of vitamin D supplementation in nonwhite populations.

Objective: To investigate factors modifying 25-hydroxyvitamin D [25(OH)D] and bioavailable 25(OH)D [25(OH)DBio] responses after vitamin D3 supplementation.

Design, setting, participants, and intervention: In this 20-week, randomized, double-blinded, placebo-controlled trial, 448 Chinese with vitamin D deficiency received 2000 IU/d vitamin D3 or placebo.

Main outcome measures: Serum 25(OH)D, vitamin D-binding protein (VDBP), parathyroid hormone (PTH) and calcium were measured, and 25(OH)DBio was calculated based on VDBP levels. Six common polymorphisms in vitamin D metabolism genes were genotyped.

Results: Between-arm net changes were +30.6 ± 1.7 nmol/L for 25(OH)D, +2.7 ± 0.2 nmol/L for 25(OH)DBio, and -5.2 ± 1.2 pg/mL for PTH, corresponding to 70% [95% confidence interval (CI), 62.8% to 77.2%] net reversion rate for vitamin D deficiency at week 20 (P < 0.001). Only 25(OH)DBio change was positively associated with calcium change (P < 0.001). Genetic factors (GC-rs4588/GC-rs7041, VDR-rs2228570, and CYP2R1-rs10741657; P ≤ 0.04) showed stronger influences on 25(OH)D or 25(OH)DBio responses than nongenetic factors, including baseline value, body mass index, and sex. An inverse association of PTH-25(OH)D was demonstrated only at 25(OH)D of <50.8 (95% CI, 43.6 to 59.0) nmol/L.

Conclusions: Supplemented 2000 IU/d vitamin D3 raised 25(OH)D and 25(OH)DBio but was unable to correct deficiency in 25% of Chinese participants, which might be partially attributed to the effect of genetic modification. More studies are needed to elucidate appropriate vitamin D recommendations for Asians and the potential clinical implications of 25(OH)DBio.

Trial registration: ClinicalTrials.gov NCT01998763.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / analysis
  • Calcium / blood
  • Case-Control Studies
  • Dietary Supplements
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Genotype
  • Humans
  • Male
  • Parathyroid Hormone / blood
  • Polymorphism, Single Nucleotide / genetics*
  • Prognosis
  • Vitamin D / administration & dosage
  • Vitamin D / analogs & derivatives*
  • Vitamin D Deficiency / blood*
  • Vitamin D Deficiency / drug therapy
  • Vitamin D Deficiency / genetics*
  • Vitamin D-Binding Protein / blood
  • Vitamin D-Binding Protein / genetics*
  • Young Adult

Substances

  • Biomarkers
  • Parathyroid Hormone
  • Vitamin D-Binding Protein
  • Vitamin D
  • 25-hydroxyvitamin D
  • Calcium

Associated data

  • ClinicalTrials.gov/NCT01998763