The 3 Epimer of 25-Hydroxycholecalciferol Is Present in the Circulation of the Majority of Adults in a Nationally Representative Sample and Has Endogenous Origins

Fundamental knowledge gaps in relation to the 3 epimer of 25-hydroxycholecalciferol [3-epi-25(OH)D-3] limit our understanding of its relevance for vitamin D nutrition and health. The aims of this study were to characterize the 3-epi-25(OH)D-3 concentrations in a nationally representative sample of adults and explore its determinants. We also used data from a recent randomized controlled trial (RCT) of supplemental cholecalciferol (vitamin D-3) conducted in winter in older adults to directly test the impact of changes in vitamin D status on serum 3-epi-25(OH)D-3 concentrations. Serum 25-hydroxcycholecalciferol [25(OH)D-3] and 3-epi-25(OH)D-3 concentrations (via LC-tandem mass spectrometry) from our vitamin D-3 ROT in adults (aged >= 50 y) and data on dietary, lifestyle, and biochemical characteristics of participants of the recent National Adult Nutrition Survey in Ireland (aged 18-84 y; n = 1122) were used in the present work. In the subsample of participants who had serum 3-epi-25(OH)D-3 concentrations greater than the limit of quantification (n = 1082; 96.4%), the mean, 10th, 50th (median), and 90th percentile concentrations were 2.50, 1.05, 2.18, and 4.30 nmol/L, respectively, whereas the maximum 3-epi-25(OH)D-3 concentration was 15.0 nmol/L. A regression model [explaining 29.9% of the variability in serum 3-epi-25(OH)D-3] showed that age >50 y, vitamin D supplement use, dietary vitamin D, meat intake, season of blood sampling, and sun exposure habits were significant positive determinants, whereas increasing waist circumference and serum 25-hydroxyergocalciferol concentration were significant negative determinants. The ROT data showed that mean serum 25(OH)D-3 and 3-epi-25(OH)D-3 concentrations increased (49.3% and 42.1%, respectively) and decreased (-28.0% and -29.1%, respectively) significantly (P < 0.0001) with vitamin D-3 (20 mu g/d) and placebo supplementation, respectively, over 15 wk of winter. In conclusion, we provide data on serum 3-epi-25(OH)D-3 in a nationally representative sample of adults. Our combined observational and ROT data might suggest that both dietary supply and dermal synthesis of vitamin D-3 contribute to serum 3-epi-25(OH)D-3 concentration. This trial was registered at clinicaltrials.gov as NCT01990872.