It is investigated whether at realistic dietary intake bixin and crocetin could induce peroxisome proliferator‐activated receptor γ (PPARγ)‐mediated gene expression in humans using a combined in vitro–in silico approach.
Concentration–response curves obtained from in vitro PPARγ‐reporter gene assays are converted to in vivo dose–response curves using physiologically based kinetic modeling‐facilitated reverse dosimetry, from which the benchmark dose levels resulting in a 50% effect above background level (BMD 50) are predicted and subsequently compared to dietary exposure levels. Bixin and crocetin activated PPARγ‐mediated gene transcription in a concentration‐dependent manner with similar potencies. Due to differences in kinetics, the predicted BMD 50 values for in vivo PPARγ activation are about 30‐fold different, amounting to 115 and 3505 mg kg bw −1 for crocetin and bixin, respectively. Human dietary and/or supplemental estimated daily intakes may reach these BMD 50 values for crocetin but not for bixin, pointing at better possibilities for in vivo PPARγ activation by crocetin.
Beneficial health effects of bixin and crocetin are suggested via activation of peroxisome proliferator‐activated receptor γ (PPARγ). However, it remains unclear whether PPARγ activation can be achieved at realistic human estimated daily intake levels. A combined in vitro, physiologically based kinetic modeling can predict the effects of functional food ingredients in human without the need for a human intervention study.