Higher 25(OH)D2 is associated with lower 25(OH)D3 and 1,25(OH)2D3

J Clin Endocrinol Metab. 2014 Aug;99(8):2736-44. doi: 10.1210/jc.2014-1069. Epub 2014 May 14.


Context: Despite common use of supplemental vitamin D2 in clinical practice, the associations of serum vitamin D2 concentrations with other vitamin D metabolites and total vitamin D are unclear.

Objective: The aim of the study was to measure vitamin D2 and D3 levels and examine their associations with each other and with total vitamin D.

Design: We performed a cross-sectional analysis of 679 randomly selected participants from the Osteoporotic Fractures in Men Study. 25-Hydroxyvitamin D2 [25(OH)D2], 25(OH)D3, 1,25-dihydroxyvitamin D2 [1,25(OH)2D2], and 1,25(OH)2D3 were measured using liquid chromatography-tandem mass spectrometry and were summed to obtain total 25(OH)D and 1,25(OH)2D. Associations between all metabolites (D2, D3, and total levels) were examined using Wilcoxon rank-sum tests and Spearman correlations.

Results: 25(OH)D2 and 1,25(OH)2D2 were detectable in 189 (27.8%) and 178 (26.2%) of the men, respectively. Higher 25(OH)D2 levels did not correlate with higher total 25(OH)D (r = 0.10; P = .17), although median total 25(OH)D was slightly higher in those with detectable vs undetectable 25(OH)D2 (25.8 vs 24.3 ng/mL; P < .001). 25(OH)D2 was not positively associated with total 1,25(OH)2D levels (r = -0.11; P = .13), and median 1,25(OH)2D level was not higher in those with detectable vs undetectable 25(OH)D2. Higher 25(OH)D2 was associated with lower 25(OH)D3 (r = -0.35; P < .001) and 1,25(OH)2D3 (r = -0.32; P < .001), with median levels of both D3 metabolites 18-35% higher when D2 metabolites were undetectable.

Conclusions: In a cohort of older men, 25(OH)D2 is associated with lower levels of 25(OH)D3 and 1,25(OH)2D3, suggesting that vitamin D2 may decrease the availability of D3 and may not increase calcitriol levels.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 25-Hydroxyvitamin D 2 / blood*
  • Aged
  • Aged, 80 and over
  • Blood Chemical Analysis / methods
  • Calcifediol / blood*
  • Calcitriol / blood*
  • Chromatography, Liquid
  • Cohort Studies
  • Cross-Sectional Studies
  • Humans
  • Male
  • Osteoporotic Fractures / blood*
  • Osteoporotic Fractures / epidemiology
  • Tandem Mass Spectrometry


  • 25-Hydroxyvitamin D 2
  • Calcitriol
  • Calcifediol