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Absorption, Metabolism and Excretion of Dietary Polyphenolic Bioactives in Humans

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ClinicalTrials.gov Identifier: NCT03194620
Recruitment Status : Completed
First Posted : June 21, 2017
Last Update Posted : November 6, 2017
Sponsor:
Collaborator:
Mars, Inc.
Information provided by (Responsible Party):
University of California, Davis

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Healthy Other: Thearubigins Other: Theaflavins Other: Procyanidin Dimer B2 (DB2) Other: (-)-Epigallocatechin-3-O-gallate (EGCG) Other: (-)-Epicatechin-3-O-gallate (ECG) Other: (-)-Epicatechin (EC) Other: (-)-Epigallocatechin (EGC) Other: Control Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Randomized, double-masked and cross-over dietary intervention study in healthy young adult males
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Absorption, Metabolism and Excretion of Dietary Polyphenolic Bioactives in Humans
Actual Study Start Date : August 2016
Actual Primary Completion Date : January 12, 2017
Actual Study Completion Date : January 12, 2017

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




Primary Outcome Measures :
  1. 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.

  2. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   25 Years to 60 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03194620


Locations
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United States, California
UC Davis
Davis, California, United States, 95616
Sponsors and Collaborators
University of California, Davis
Mars, Inc.
Investigators
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Principal Investigator: Carl L Keen, PhD UC Davis
Study Director: Javier I Ottaviani, PhD Mars, Inc.
Publications:

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Responsible Party: University of California, Davis
ClinicalTrials.gov Identifier: NCT03194620    
Other Study ID Numbers: 907244
First Posted: June 21, 2017    Key Record Dates
Last Update Posted: November 6, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Only researchers listed in the protocol and approved by the IRB will have access to IPD.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of California, Davis:
Flavanols
Cocoa Flavanols
Epicatechins
Polyphenols
Procyanidins
EGCG
EGC
ECG
Theaflavins
Thearubigins
Additional relevant MeSH terms:
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Proanthocyanidin
Epigallocatechin gallate
Epicatechin gallate
Procyanidin
Theaflavin
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Chelating Agents
Sequestering Agents
Antimutagenic Agents
Anticarcinogenic Agents
Antineoplastic Agents
Neuroprotective Agents
Antineoplastic Agents, Phytogenic
Protease Inhibitors
Enzyme Inhibitors