C3-epimerization of 25-hydroxyvitamin D increases with increasing serum 25-hydroxyvitamin D levels and shows a high degree of tracking over time.

OBJECTIVE: Evaluate the effects of serum 25-hydroxyvitamin D (25(OH)D) levels, vitamin D binding protein (DBP) and genetic factors on C3-epimerization of 25(OH)D and follow the tracking of the epimer during one year.

DESIGN: Cross-sectional and longitudinal study.

METHODS: Data from eight previously conducted, Tromsø based studies (3 observational, 5 randomized controlled trials) were combined. 25(OH)D serum samples were re-analyzed with a LC-MS/MS method that also resolves and measures the metabolite C3-epi-25(OH)D3 . Data on vitamin D binding protein (DBP) phenotype (based on single nucleotide polymorphisms (SNPs) rs4588 and rs7041) and genetic determinants for serum 25(OH)D (SNPs rs2282679, rs10741657, rs3829251 and rs6013897) were collected where available.

RESULTS: 2219 subjects were included. Median (5th, 95th percentiles) baseline serum values of 25(OH)D3 , C3-epi-25(OH)D3 , and %-C3-epi-25(OH)D3 were 49.1 (22.1, 92.8) nmol/L, 2.3 (0.9, 6.0) nmol/L and 4.4 (2.7, 8.4) %, respectively. The highest baseline values were 230.5 nmol/L for 25(OH)D3 , 79.7 nmol/L for C3-epi-25(OH)D3 and 48.2% for %-C3-epi-25(OH)D3 . There was a strong correlation between serum 25(OH)D3 and C3-epi-25(OH)D3 . The %-C3-epi-25(OH)D3 value increased with increasing serum 25(OH)D3 , but leveled off at ~7% at a 25(OH)D3 concentration of ~120-140 nmol/L. There was a significant degree of tracking for %-C3-epi-25(OH)D3 (correlation coefficient rho between baseline and 1-year values 0.39, P < 0.001). The %-C3-epi-25(OH)D3 level was not related to serum DBP level, DBP phenotype nor to SNPs related to serum 25(OH)D3 level. The serum 25(OH)D3 level could explain less than 3% of %-C3-epi-25(OH)D3 variation.

CONCLUSIONS: There are considerable individual and reproducible differences in percent C3-epimerization of uncertain clinical importance.