Bioavailability and Metabolism of N-Trans Caffeoyltyramine and N-Trans Feruloyltyramine - A Narrative Review

Insights into the bioavailability of hemp derived phenolic amides N-trans caffeoyltyramine (NCT) and N-trans feruloyltyramine (NFT) remained limited to experimental data from preclinical in vitro and animal systems. However, the bioavailability of similar phenolics and phenolic amides from other sources has been experimentally determined. This concise review summarizes the current state of knowledge for phenolic amides with the goal of providing experimental guidance on the assessment of NCT and NFT from hemp ingredients in humans. Evidence from phenolic and avenanthramide (similar phenolic amides from oats) suggest that overall absorption of free phenolic amides would be limited in humans to <2% of native forms. Metabolites derived by both host (conjugated Phase II metabolites) and microbial fermentation products would likely represent the main compounds in circulation derived from NCT or NFT intake. This would be extensively influenced by the matrix provided including hemp-based ingredients with large portions of physically and chemically bound NCT and NFT forms that are not absorbable. Experimental designs to determine NCT and NFT response in humans would need to consider longer exposure and collection periods to adequately capture 24 and 48h urine and blood samples likely to have key NCT and NFT derived microbial and host metabolites present. Considering adaptation of the microbiota to these compounds it is likely that a robust design would also include a dimension of long-term exposure to enable detection of target metabolites derived from hemp NCT and NFT.