Comparative biokinetics and metabolism of pure monomeric, dimeric, and polymeric flavan-3-ols: a randomized cross-over study in humans

Mol Nutr Food Res. 2015 Apr;59(4):610-21. doi: 10.1002/mnfr.201400422. Epub 2015 Feb 18.

Abstract

Scope: Flavan-3-ols are abundant polyphenols in human nutrition and are associated with beneficial health effects. The aim of this study was to comparatively investigate the metabolic fate of (-)-epicatechin, procyanidin B1, and polymeric procyanidins in a randomized cross-over study in humans.

Methods and results: Parent compounds, conjugates, and microbial metabolites were determined in plasma, urine, and faeces by HPLC-MS and GC-MS/MS. Glucuronidated, sulfated, and methylated (-)-epicatechin and 5-(3',4'-dihydroxyphenyl)-valerolactone were the dominant metabolites in blood and urine. In addition, minor amounts of procyanidin B1 and 4-hydroxy-5-(3',4'-dihydroxyphenyl)valeric acid and their conjugated metabolites were detected. The formation of 5-(3',4'-dihydroxyphenyl)-valerolactone and 4-hydroxy-5-(3',4'-dihydroxyphenyl)valeric acid varied largely between individuals as well as with the degree of polymerization of flavan-3-ols. Monomer units were not detectable in plasma or urine after procyanidin B1 and polymeric procyanidin intake. No correlation was found between the intake of flavan-3-ols and the occurrence of phenolic acids in blood and urine or the phenolic compound profiles in faeces.

Conclusion: In addition to conjugated metabolites derived from the absorption of monomeric flavan-3-ols, 5-(3',4'-dihydroxyphenyl)-valerolactone represents an important in vivo metabolite of (-)-epicatechin and procyanidin B1 produced by the gut microbiota.

Keywords: Bioavailability; Catechins; Drug metabolism; Microbial degradation; Procyanidins.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biflavonoids / pharmacokinetics*
  • Body Mass Index
  • Cacao / chemistry
  • Catechin / pharmacokinetics*
  • Chromatography, High Pressure Liquid
  • Creatinine / urine
  • Cross-Over Studies
  • Feces / chemistry
  • Flavonoids / pharmacokinetics*
  • Humans
  • Lactones / pharmacokinetics
  • Male
  • Plant Extracts / chemistry
  • Polymerization
  • Polymers / administration & dosage*
  • Polyphenols / pharmacokinetics
  • Proanthocyanidins / pharmacokinetics*
  • Tandem Mass Spectrometry
  • Young Adult

Substances

  • (-)-5-(3',4'-dihydroxyphenyl)-valerolactone
  • Biflavonoids
  • Flavonoids
  • Lactones
  • Plant Extracts
  • Polymers
  • Polyphenols
  • Proanthocyanidins
  • procyanidin B1
  • flavan-3-ol
  • procyanidin
  • Catechin
  • Creatinine