Carotenoid metabolites, their tissue and blood concentrations in humans and further bioactivity via retinoid receptor-mediated signalling

Many epidemiological studies have emphasised the relation between carotenoid dietary intake and their circulating concentrations and beneficial health effects, such as lower risk of cardiometabolic diseases and cancer. However, there is dispute as to whether the attributed health benefits are due to native carotenoids or whether they are instead induced by their metabolites. Several categories of metabolites have been reported, most notably involving (a) modifications at the cyclohexenyl ring or the polyene chain, such as epoxides and geometric isomers, (b) excentric cleavage metabolites with alcohol-, aldehyde- or carboxylic acid-functional groups or (c) centric cleaved metabolites with additional hydroxyl, aldehyde or carboxyl functionalities, not counting their potential phase-II glucuronidated / sulphated derivatives. Of special interest are the apo-carotenoids, which originate in the intestine and other tissues from carotenoid cleavage by β-carotene oxygenases 1/2 in a symmetrical / non-symmetrical fashion. These are more water soluble and more electrophilic and, therefore, putative candidates for interactions with transcription factors such as NF-kB and Nrf2, as well as ligands for RAR-RXR nuclear receptor interactions. In this review, we discuss in vivo detected apo-carotenoids, their reported tissue concentrations, and potential associated health effects, focusing exclusively on the human situation and based on quantified / semi-quantified carotenoid metabolites proven to be present in humans.