Plasma pharmacokinetics of (poly)phenol metabolites and catabolites after ingestion of orange juice by endurance trained men

• Published in: Free radical biology & medicine 2020-11, Vol.160, p.784-795
• Main Authors: Pereira-Caro, Gema, Clifford, Michael N., Polyviou, Thelma, Ludwig, Iziar A., Alfheeaid, Hani, Moreno-Rojas, José Manuel, Garcia, Ada L., Malkova, Dalia, Crozier, Alan
• Format: Article
• Language: English
• Subjects: 3-Hydroxy-3-(phenyl)propanoic acids; Absorption; Citrus sinensis; Eating; Fruit and Vegetable Juices; Humans; Male; Metabolites; Microbial catabolites; Orange juice (poly)phenols; Phenol; Phenols; Potential bioactivity
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2020.09.007

The health benefits of orange juice (OJ) consumption are attributed in part to the circulating flavanone phase II metabolites and their microbial-derived ring fission phenolic catabolites. The present study investigated these compounds in the bloodstream after acute intake of 500 mL of OJ. Plasma samples obtained at 0, 1, 2, 3, 4, 5, 6, 7, 8 and 24 h after OJ intake were analysed by HPLC-HR-MS. Eleven flavanone metabolites and 36 phenolic catabolites were identified and quantified in plasma. The main metabolites were hesperetin-3′-sulfate with a peak plasma concentration (Cmax) of 80 nmol/L, followed by hesperetin-7-glucuronide (Cmax 24 nmol/L), hesperetin-3′-glucuronide (Cmax 18 nmol/L) and naringenin-7-glucuronide (Cmax 21 nmol/L). Among the main phenolic catabolites to increase in plasma after OJ consumption were 3′-methoxycinnamic acid-4′-sulfate (Cmax 19 nmol/L), 3-hydroxy-3-(3′-hydroxy-4′-methoxyphenyl)propanoic acid (Cmax 20 nmol/L), 3-(3′-hydroxy-4′-methoxyphenyl)propanoic acid (Cmax 19 nmol/L), 3-(4′-hydroxyphenyl)propanoic acid (Cmax 25 nmol/L), and 3-(phenyl)propanoic acid (Cmax 19 nmol/L), as well as substantial amounts of phenylacetic and hippuric acids. The comprehensive plasma pharmacokinetic profiles that were obtained are of value to the design of future ex vivo cell studies, aimed at elucidating the mechanisms underlying the potential health benefits of OJ consumption. This trial was registered at clinicaltrials.gov as NCT02627547. [Display omitted] •Human absorption and metabolism of orange juice (poly)phenols.•Mammalian and microbiota-mediated conversions.•Plasma pharmacokinetic of flavanone metabolites and catabolites.•Unexpected behaviour of 3-hydroxy-3-(phenyl)propanoic acids highlighted.•Essential data for ex vivo cell studies on the protective effects of flavanones.