Food Matrix Effect on Flavanol Absorption, Metabolism and Excretion: Methylxanthines
Condition: Healthy
Study type: Interventional

Summary: 
      Dietary intervention study in healthy young adult males to evaluate concentration of flavanol
      metabolites in plasma and urine after single acute intakes of methylxanthines.
    

Detailed description: 
      Flavonoids, including the sub groups of Flavanols (F) are plant-derived compounds commonly
      present in the human diet. Examples of F-containing foods and beverages are apples,
      chocolate, tea, wine, berries, pomegranate and nuts. The consumption of F-containing foods
      and beverages has been associated with improvements in cardiovascular health. In this
      context, there exists a great interest in describing the absorption, metabolism and excretion
      of F in humans, as it is thought that F-derived metabolites present in circulation are the
      mediators of F-beneficial effects in humans. Recently, the investigators described a series
      of F-derived metabolites in circulation that are present after the consumption of a single
      acute intake amount of F in humans as well as F-metabolites derived from the metabolic
      activity of the gut microbiome. A key question, however, is if the metabolites the
      investigators observed after a single acute feeding are the same as those that occur in
      individuals who consume F-rich diets on a regular basis. Studies investigating the metabolism
      of numerous other xenobiotics have shown that the profile of metabolites can greatly vary
      over time, as well as with the amount of the xenobiotic ingested. In this context, the
      investigators submit it is important to assess whether or not there are food matrix-dependent
      effects on the levels and profile of F-derived metabolites in humans. The investigators
      suggest the information that will be obtained from the outlined work will be particularly
      timely given ongoing discussion concerning the possible generation of dietary recommendations
      for F-rich foods and increasing interest in the putative health effects of F intake in
      humans.

      Following the beginning of the trial, an advanced method to analyze cocoa flavanols was
      accredited by AOAC International as a First Action Official Method of Analysis
      https://doi.org/10.1093/jaoacint/qsaa132). This updated method relies on a reference material
      (RM8403) recently standardized and made commercially available by the U.S. National Institute
      of Standards and Technology. While the actual cocoa flavanol content of our intervention
      remained unchanged throughout the trial, the application of this new analytical method led to
      expected changes in how the total cocoa flavanol content is now reported. Applying AOAC
      2020.05/RM8403 to our intervention, the total cocoa flavanol content of select arms in our
      trials have been updated accordingly.
    

Intervention name(s): CF Control; CF-Theobromine; CF-Caffeine
Intervention type(s): Other; Other; Other
Intervention description(s): CF Control: 587 mg of cocoa flavanols, <1 mg caffeine and <1 mg theobromine; CF-Theobromine: 575 mg of cocoa flavanols, 11 mg caffeine and 93 mg theobromine; CF-Caffeine: 587 mg of cocoa flavanols, 112 mg caffeine and <1 mg theobromine
Intervention MeSH terms: Theobromine; Caffeine
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Dietary intervention study in healthy young adult males
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: flavanol; ADME; polyphenols; cocoa; epicatechin; methylxanthine; caffeine