Vitamin D C3-epimer levels are proportionally higher with oral vitamin D supplementation compared to ultraviolet irradiation of skin in mice but not humans

A proportion of circulating 25-hydroxy vitamin D3 (25(OH)D-3)) undergoes epimerization to form C3-epi 25(OH) D-3 and C3-epi 1,25(OH)(2)D-3. These epimers have less calcaemic activity than non-epimerized metabolites and are not differentiated by many immunoassays when reporting total 25(OH)D-3 levels. This study aimed to compare the effect of exposure to ultraviolet radiation (UVR) and oral vitamin D-3 supplementation on vitamin D C3-epimer levels. C57B1/6 female mice were fed either vitamin D-sufficient (vitamin D-3 2000 IU/kg) or- deficient diets (no vitamin D-3) for 4 weeks. Among the vitamin D-deficient group, the shaved backs of half were irradiated daily for 4 days with 1 kJ/m(2) UVR, followed by twice weekly irradiation for 4 weeks. Despite similar 25(OH)D-3 levels, the UV-irradiated group had a lower proportion of C3-epi 25(OH)D-3 at week 7 (p < 0.05) and week 9 (p < 0.01). C3-epimer concentrations and %C3-epi 25(OH)D-3 were also analysed in serum samples from two human clinical trials. These trials investigated the effect of high dose oral vitamin D-3 supplementation and narrowband UVB phototherapy, respectively. Serum 25(OH)D-3 and the %C3-epi 25(OH)D-3 levels measured at 12 months after oral vitamin D-3 supplementation were not significantly different to those measured at the time of maximal effect of phototherapy (2 months). Thus, the proportion of 25(OH)D-3 that undergoes epimerization is greater with oral vitamin D-3 supplementation than exposure to UVR in mice, but not in humans. This important difference between human and murine vitamin D metabolism warrants consideration when interpreting animal studies.