Absorption, Metabolism and Excretion of Dietary Polyphenolic Bioactives in Humans

October 31, 2017 updated by: University of California, Davis
The objectives of this study are to i) describe the absorption, distribution, metabolism and excretion (ADME) and pharmacokinetic parameters of selected dietary (poly)phenols in humans; and ii) to compare the ADME and pharmacokinetic parameters of selected dietary (poly)phenols in humans.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Dietary (poly)phenols are a large group of bioactive food constituents that can be classified in flavonoids, stilbenes, lignans and phenolic acids. Flavonoids can be subclassified in different subgroups, including but not limited to flavanols (e.g. (-)-epicatechin, (+)-catechin, procyanidins, EGCG, EGC, etc) and flavones (apigenin and luteolin). Examples of flavanol-containing foods and beverages are apples, chocolate, tea, wine, berries, pomegranate and nuts. Examples of flavone-containing foods and beverages are parsley, celery, and chamomile.

(Poly)phenolic bioactives are actively investigated for their putative beneficial health effects in humans. In this context, understanding the ADME of dietary (poly)phenols is recognized as a key step to gain insight into the nutritional and biomedical relevance of this group of compounds. Understanding the ADME of polyphenols may aid towards i) the identification of metabolites as potential nutritional biomarkers of (poly)phenol consumption, ii) the identification of potential active metabolites mediating the effects observed after (poly)phenol intake, and iii) the design and execution of dietary intervention studies aiming at assess safety and efficacy of (poly)phenols.

Over the last years, significant progress has been made on the description of the ADME of certain (poly)phenols. The investigators recently described the ADME of (-)-epicatechin. However, there is still need to understand the ADME of other polyphenolic bioactives as well as the importance of the role of the gut microbiome in the metabolism of these compounds. In this context, the investigators aim at describing and comparing the ADME of dietary polyphenolic bioactives in humans. To accomplish this, the investigators propose conducting a randomized, double-masked and cross-over dietary intervention study in healthy young adult males. The investigators will evaluate the concentration of polyphenol-derived metabolites in plasma and urine after single acute intakes of polyphenol-containing test materials on 8 different test days.

Study Type

Interventional

Enrollment (Actual)

12

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

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

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • 25-60 years old males
  • No prescription medications
  • BMI 18.5 - 34.9 kg/m2
  • Weight ≥ 110 pounds
  • previously consumed cocoa, peanut, parsley, celery and chamomile products with no adverse reactions

Exclusion Criteria:

  • Adults unable to consent
  • Females
  • Prisoners
  • Non-English speaking*
  • BMI ≥ 35 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 either 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 Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Control
Single oral intake of flavanol-free fruit-flavored non-dairy drink
Other: Control
Single oral intake of a flavanol-free, fruit flavored, non-dairy drink.
Experimental: Theaflavins
Single oral intake of a fruit-flavored non-dairy drink containing a mixture of theaflavins
Other: Theaflavins
Single oral intake of 120 µmol of an equimolar mixture of theaflavins (isolated from black tea) in a flavanol-free, fruit flavored, non-dairy drink. The theaflavin mix includes theaflavin, theaflavin-3-gallate and theaflavin-3,3'-gallate
Experimental: Procyanidin Dimer B2 (DB2)
Single oral intake of a fruit-flavored non-dairy drink containing Procyanidin Dimer B2 (DB2)
Other: Procyanidin Dimer B2 (DB2)
Single oral intake of 120 µmol of Procyanidin Dimer B2 (DB2) (isolated from Theobroma cacao) in a flavanol-free, fruit flavored, non-dairy drink.
Experimental: (-)-Epigallocatechin-3-O-gallate (EGCG)
Single oral intake of a fruit-flavored non-dairy drink containing (-)-Epigallocatechin-3-O-gallate (EGCG)
Other: (-)-Epigallocatechin-3-O-gallate (EGCG)
Single oral intake of 120 µmol of (-)-Epigallocatechin-3-O-gallate (EGCG)(isolated from green tea) in a flavanol-free, fruit flavored, non-dairy drink.
Experimental: (-)-Epicatechin-3-O-gallate (ECG)
Single oral intake of a fruit-flavored non-dairy drink containing (-)-Epicatechin-3-O-gallate (ECG)
Other: (-)-Epicatechin-3-O-gallate (ECG)
Single oral intake of 120 µmol of (-)-Epicatechin-3-O-gallate (ECG) (isolated from green tea) in a flavanol-free, fruit flavored, non-dairy drink.
Active Comparator: (-)-Epicatechin (EC)
Single oral intake of a fruit-flavored non-dairy drink containing (-)-Epicatechin (EC)
Other: (-)-Epicatechin (EC)
Single oral intake of 120 µmol of (-)-Epicatechin (EC) (isolated from green tea) in a flavanol-free, fruit flavored, non-dairy drink.
Experimental: (-)-Epigallocatechin (EGC)
Single oral intake of a fruit-flavored non-dairy drink containing (-)-Epigallocatechin (EGC)
Other: (-)-Epigallocatechin (EGC)
Single oral intake of 120 µmol of (-)-Epigallocatechin (EGC) (isolated from green tea) in a flavanol-free, fruit flavored, non-dairy drink.
Experimental: Thearubigins
Single oral intake of a fruit-flavored non-dairy drink containing thearubigins
Other: Thearubigins
Single oral intake of 94.9 mg of therubigins (isolated from black tea) in a flavanol-free, fruit flavored, non-dairy drink

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in the concentration of flavanol metabolites in urine.
Time Frame: Urine collected 12h previous to intervention and up to 24 h after intervention
Flavanol metabolites include gut microbiome derived metabolites include conjugates of 5-(3',4'-dihydroxyphenyl)-g-valerolactone metabolites and structurally related flavanol conjugated metabolites.
Urine collected 12h previous to intervention and up to 24 h after intervention
Changes in the concentration of flavanol metabolites in plasma
Time Frame: Plasma collected before (0h) and up to 6h post intervention
Flavanol metabolites include gut microbiome-derived metabolites like 5-(3',4'-dihydroxyphenyl)-g-valerolactone and structurally related flavanol conjugated metabolites.
Plasma collected before (0h) and up to 6h post intervention

Collaborators and Investigators

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

Sponsor

University of California, Davis

Collaborators

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)

August 1, 2016

Primary Completion (Actual)

January 12, 2017

Study Completion (Actual)

January 12, 2017

Study Registration Dates

First Submitted

June 19, 2017

First Submitted That Met QC Criteria

June 19, 2017

First Posted (Actual)

June 21, 2017

Study Record Updates

Last Update Posted (Actual)

November 6, 2017

Last Update Submitted That Met QC Criteria

October 31, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 907244

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

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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