Endocrine Abstracts

Introduction: Vitamin D metabolites are key biomarkers for bone health, immune function, and chronic disease risk. Recent evidence indicates that phase II metabolites of vitamin D, may act as reservoir forms rather solely excretory products. However, the specific human sulfotransferases (SULTs) responsible for sulfating individual vitamin D metabolites remain poorly defined. Furthermore, population-level differences in sulfation capacity, potentially influenced by genetic differences, has not been systematically examined.

Methods: Vitamin D metabolites were incubated with 11 different recombinant human SULT isoforms to assess their sulfation activity. Resulting sulfate conjugates were quantified using LC-MS/MS. In parallel, 150 different human serum samples were analysed by LC-MS/MS to evaluate inter-individual and potential population-based differences in 25OHD3 sulfation.

Results: SULT2A1, SULT1A1*1, SULT1A1*2, and SULT1E1 displayed sulfation activity towards vitamin D metabolites, with variation in sulfation activity between SULTs and mono and di-hydroxy forms of vitamin D. In the human cohort, no age-based or sex-based differences were observed in 25OHD3 sulfation. However, ethnic-based differences were observed with African-Americans displaying higher proportions of sulfated 25OHD3 (52.1%; median) compared to Hispanics (51.5%; median) and Caucasians (49.5%; median). Seasonal-based differences were also observed in 25OHD3 sulfation where samples collected in autumn and winter months having a higher proportion of sulfated 25OHD3.

Discussion: This study identifies the human SULTs involved in vitamin D conjugation metabolism and highlights factors that influence sulfation in humans. The observed ethnic and seasonal differences in 25OHD3 sulfation imply that both individual and environmental factors may regulate vitamin D conjugation and availability. Together, these findings enhance understanding of phase II vitamin D metabolism. Further studies will investigate the potential role of these sulfated vitamin D metabolites as storage forms, and its potential role in defining a more accurate assessment in vitamin D status.