Mind the gap—deficits in our knowledge of aspects impacting the bioavailability of phytochemicals and their metabolites—a position paper focusing on carotenoids and polyphenols

Abstract

Various secondary plant metabolites or phytochemicals, including polyphenols and carotenoids, have been associated with a variety of health benefits, such as reduced incidence of type 2 diabetes, cardiovascular diseases, and several types of cancer, most likely due to their involvement in ameliorating inflammation and oxidative stress. However, discrepancies exist between their putative effects when comparing observational and intervention studies, especially when using pure compounds. These discrepancies may in part be explained by differences in intake levels and their bioavailability. Prior to exerting their bioactivity, these compounds must be made bioavailable, and considerable differences may arise due to their matrix release, changes during digestion, uptake, metabolism, and biodistribution, even before considering dose‐ and host‐related factors. Though many insights have been gained on factors affecting secondary plant metabolite bioavailability, many gaps still exist in our knowledge. In this position paper, we highlight several major gaps in our understanding of phytochemical bioavailability, including effects of food processing, changes during digestion, involvement of cellular transporters in influx/efflux through the gastrointestinal epithelium, changes during colonic fermentation, and their phase I and phase II metabolism following absorption.

Characteristics and Health Benefits of Phytochemicals

“…Of particular relevance are human studies, especially epidemiological and intervention studies, and biomarker-related studies. There is mutual agreement among experts that only part of the potential effects of phytochemicals has been sufficiently investigated to come to final recommendations [9]. In the following, the results of some of the more recent publications concerning wide-spread non-communicable diseases are presented.…”

Overview of carotenoid bioavailability determinants: From dietary factors to host genetic variations

“…This review underlines the 595 vast amount of work still needed to improve our knowledge of carotenoid absorption and its 596 modulating factors ("SLAMENGHI") (see (Bohn, et al, 2015) for a recent review). Indeed, 597 several key points still need to be investigated: 598 • Carotenoid bioavailability displays a relatively high variability.…”

How to overcome ATP-binding cassette drug efflux transporter-mediated drug resistance?

“…However, further investigation is needed to define optimal dose schedules of flavonoids capable of inducing ABC transporter inhibition [219] . Future studies would also have to take into account flavonoid pharmacokinetics, bioavailability and activity of flavonoid metabolites after ingestion, which would reduce active flavonoid plasma concentrations [222,223] .…”