*Geek Box: (Poly)phenol Metabolites
The metabolism of (poly)phenols has been of particular interest in trying to link their purported health benefits to biological plausibility. For the brain, this became even more puzzling when it was recognised that flavonoids do not cross the blood-brain barrier in significant quantities. There was also the fact that the parent compound, i.e., the form of the compound ingested whole through the diet, may have peak concentrations of only between 1-6hrs.
However, there is now a greater understanding of the metabolism and bioavailability of (poly)phenolic compounds. Some (poly)phenols may be absorbed directly to the liver from the small intestine, where they undergo metabolism in the liver through a process known as ‘first pass metabolism’, similar to what drugs undergo. Remember: because these compounds are not recognised as nutrients by the body, they are treated as xenobiotic agents and are metabolised through the liver in the same way drugs would be. This is, in fact, critical to their benefits, because this process produces a diverse array of metabolites which are then released from the liver back into the circulation.
(Poly)phenols also pass to the colon and, like fibre, undergo degradation by gut bacteria into phenolic metabolites, which are in turn absorbed in quantities far exceeded the levels absorbed from the small intestine. These metabolite compounds absorbed from the colon also pass through the liver, undergoing more extensive metabolism. Finally, enterohepatic circulation [the recycling of compounds between the liver and digestive tract via the hepatic portal vein] is another route of (poly)phenol metabolite circulation, as certain metabolites may be recycled up to 20 times!
An enormous array of metabolites have been identified, for example up to 62 anthocyanin metabolites have been identified to date. These metabolites may be up to 100-fold greater in concentration than the parent compounds, and have significantly higher bioavailability. The fact that their continued metabolism and recycling means a bioavailability of up to 48hrs provides a plausible mechanistic explanation for chronic benefits observed in long-term cohort studies. For the brain and cognition, this has been a particularly important finding, because rather than cross the BBB in large quantities it was recognised that low physiological concentrations of their metabolites may act through signalling pathways in the brain.