Project Details
Projekt
Bioavailability, seasonal variability, and metabolization of vitamin D-photosiomers in humans
Applicant
Dr. Franz Ewendt
Subject Area
Nutritional Sciences
Term
from 2023 to 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 522549509
UV-B exposure is crucial for the synthesis of vitamin D, which, as the active hormone calcitriol, plays a central role in mineral metabolism, bone formation, and immune response. However, sustained UV-B irradiation results in photoisomerization of previtamin D, thereby photoisomers are formed. The most abundant photoisomers are lumisterol and tachysterol. UV-B exposure of skin leads to the formation of lumisterol3 (L3) and tachysterol3 (T3). In provitamin D2-rich foods such as yeast or mushrooms the predominant photoisomers are lumisterol2 (L2) and tachysterol2 (T2). For a long time, it was assumed that cutaneous produced photoisomers are not released into the circulation and are biologically inactive. Slominski et al. were the first who found L3 and T3 in the plasma of subjects and could show their metabolism into biologically active compounds. In addition, own published data demonstrated that mice which received L2 or T2 with their diets had comparatively high concentrations of these photoisomers in their blood and tissues, showed a marked reduction in calcitriol levels and were characterized by an altered gene expression of Cyp27b1 and Cyp24a1 in the kidney. Remarkably, studies in mice and cells indicate that T2 exerts calcitriol-like effects. UV-B irradiation of ergosterol-rich foods is increasingly be used to fortify food with vitamin D. However, UV-B irradiation of food is accompanied by the formation of photoisomers. The amounts of photoisomers in these products vary considerably, but are comparable to those of vitamin D2. However, the bioavailability and metabolization of orally ingested photoisomers in humans are so far unknown. Furthermore, it is unknown whether the blood levels of endogenously formed photoisomers may vary with the seasons, similar to vitamin D. The current project is aiming to investigate the photoisomers and metabolized hydroxy-photoisomers in plasma of humans who received UV-B-treated foods. The samples for this analysis will be obtained from a randomized, controlled intervention study with 30 healthy volunteers, who received either UV-B treated mushrooms or untreated mushrooms for 7 days. The seasonal variability of photoisomer-derivatives in blood, will be analyzed in plasma of subjects from the German National Cohort Study (NAKO). The investigations on the bioavailability, metabolization and biological activity require a valid identification and quantification of the photoisomer-metabolites. The envisaged host institution (University of Alabama, Birmingham, USA, Prof. Slominski) provides an excellent research environment for measuring multiple types of photoisomers, which is a prerequisite for further development of this research topic.
DFG Programme
WBP Fellowship
International Connection
USA
