Abstract
omega-Phenyl-alkenoic acids are abundant in coffee, fruits, and vegetables. Along with omega-phenyl-alkanoic acids, they are produced from numerous dietary (poly)phenols and aromatic amino acids in vivo. This review addresses how phenyl-ring substitution and flux modulates their gut microbiota and endogenous beta-oxidation. 3',5'-Dihydroxy-derivatives (from alkyl-resorcinols, flavanols, proanthocyanidins), and 4'-hydroxy-phenolic acids (from tyrosine, p-coumaric acid, naringenin) are beta-oxidation substrates yielding benzoic acids. In contrast, 3',4',5'-tri-substituted-derivatives, 3',4'-dihydroxy-derivatives and 3'-methoxy-4'-hydroxy-derivatives (from coffee, tea, cereals, many fruits and vegetables) are poor beta-oxidation substrates with metabolism diverted via gut microbiota dehydroxylation, phenylvalerolactone formation and phase-2 conjugation, possibly a strategy to conserve limited pools of coenzyme A. 4'-Methoxy-derivatives (citrus fruits) or 3',4'-dimethoxy-derivatives (coffee) are susceptible to hepatic "reverse" hydrogenation suggesting incompatibility with enoyl-CoA-hydratase. Gut microbiota-produced 3'-hydroxy-4'-methoxy-derivatives (citrus fruits) and 3'-hydroxy-derivatives (numerous (poly)phenols) are excreted as the phenyl-hydracrylic acid beta-oxidation intermediate suggesting incompatibility with hydroxy-acyl-CoA dehydrogenase, albeit with considerable inter-individual variation. Further investigation is required to explain inter-individual variation, factors determining the amino acid to which C-6-C-3 and C-6-C-1 metabolites are conjugated, the precise role(s) of l-carnitine, whether glycine might be limiting, and whether phenolic acid-modulation of beta-oxidation explains how phenolic acids affect key metabolic conditions, such as fatty liver, carbohydrate metabolism and insulin resistance.