Food Matrix Effect on Flavanol Absorption, Metabolism and Excretion: Methylxanthines

October 6, 2022 updated by: University of California, Davis
Dietary intervention study in healthy young adult males to evaluate concentration of flavanol metabolites in plasma and urine after single acute intakes of methylxanthines.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Davis, California, United States, 95616
        • UC Davis
      • Davis, California, United States, 95616
        • Ragle Human Nutrition Research Center, Department of Nutrition at UC Davis

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

25 years to 60 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • No prescription medications
  • BMI 18.5 - 29.9 kg/m2
  • Weight ≥ 110 pounds
  • previously consumed cocoa, peanut, parsley, celery and chamomile products with no adverse reactions

Exclusion Criteria:

  • Adults unable to consent
  • Prisoners
  • Non-English speaking*
  • BMI ≥ 30 kg/m2
  • Performing vigorous physical activity (i.e. more than 6 MET; metabolic equivalence of task as defined by CDC and ACSM guidelines (http://www.cdc.gov/physicalactivity/everyone/glossary/index.html#vig-intensity; and http://www.cdc.gov/nccdphp/dnpa/physical/pdf/PA_Intensity_table_2_1.pdf ) for more than 3 days a week.
  • Dietary allergies including those to nuts, cocoa and chocolate products, parsley, celery and chamomile.
  • Active avoidance of coffee and caffeinated soft drinks
  • Under current medical supervision
  • A history of cardiovascular disease, stroke, renal, hepatic, or thyroid disease
  • History of clinically significant depression, anxiety or other psychiatric condition
  • History of Raynaud's disease
  • History of difficult blood draws
  • Indications of substance or alcohol abuse within the last 3 years
  • Current use of herbal, plant or botanical supplements (multi-vitamin/mineral supplements are allowed)
  • Blood Pressure > 140/90 mm Hg
  • GI tract disorders, previous GI surgery (except appendectomy)
  • Self-reported malabsorption (e.g. difficulty digesting or absorbing nutrients from food, potentially leading to bloating, cramping or gas)
  • Diarrhea within the last 3 months, or antibiotic intake within the last 3 months
  • Vegetarian, Vegan, food faddists, individuals using non-traditional diets, on a weight loss diet or individuals following diets with significant deviations from the average diet
  • Metabolic panel and cholesterol results or complete blood counts that are outside of the normal reference range and are considered clinically relevant by the study physician
  • Cold, flu, or upper respiratory condition at screening
  • Currently participating in a clinical or dietary intervention study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: CF Control
CF Control: 587 mg of cocoa flavanols (101 mg epicatechin), <1 mg caffeine and <1 mg theobromine
Other: CF Control
CF Control: 587 mg of cocoa flavanols, <1 mg caffeine and <1 mg theobromine
EXPERIMENTAL: CF-Theobromine
CF-Theobromine: 575 mg of cocoa flavanols (102 mg epicatechin), 11 mg caffeine and 93 mg theobromine
Other: CF-Theobromine
CF-Theobromine: 575 mg of cocoa flavanols, 11 mg caffeine and 93 mg theobromine
EXPERIMENTAL: CF-Caffeine
CF-Caffeine: 587 mg of cocoa flavanols (101 mg epicatechin), 112 mg caffeine and <1 mg theobromine(Experimental)
Other: CF-Caffeine
CF-Caffeine: 587 mg of cocoa flavanols, 112 mg caffeine and <1 mg theobromine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Flavanol metabolites in plasma
Time Frame: Before to 6 h post test material intake
Plasma concentration of flavanol metabolites
Before to 6 h post test material intake
Flavanol metabolites in urine
Time Frame: 12 h before to 24 h post test material intake
Amount of flavanols metabolites excreted in urine
12 h before to 24 h post test material intake

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Methylxanthines in plasma
Time Frame: Before to 6 h post test material intake
Plasma concentration of methylxanthines and methylxanthine metabolites
Before to 6 h post test material intake
Methylxanthines in urine
Time Frame: 12 h before to 24 h post test material intake
Amount of methylxanthines and methylxanthine metabolites excreted in urine
12 h before to 24 h post test material intake

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, Davis

Collaborators

Mars, Inc.

Investigators

  • Principal Investigator: Carl L Keen, PhD, Mars, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

February 16, 2017

Primary Completion (ACTUAL)

May 31, 2017

Study Completion (ACTUAL)

May 31, 2017

Study Registration Dates

First Submitted

May 3, 2018

First Submitted That Met QC Criteria

May 3, 2018

First Posted (ACTUAL)

May 16, 2018

Study Record Updates

Last Update Posted (ACTUAL)

October 10, 2022

Last Update Submitted That Met QC Criteria

October 6, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 429275-T

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Only researchers listed in the protocol and approved by the IRB will have access to IPD.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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