Absorption, Metabolism and Excretion of Dietary Polyphenolic Bioactives in Humans

Not Applicable

Completed

• Conditions: Healthy
• Interventions: Other: Control; Other: Procyanidin Dimer B2 (DB2); Other: Thearubigins; Other: (-)-Epicatechin (EC); Other: Theaflavins; Other: (-)-Epigallocatechin (EGC); Other: (-)-Epigallocatechin-3-O-gallate (EGCG); Other: (-)-Epicatechin-3-O-gallate (ECG)

• Registration Number: NCT03194620
• Lead Sponsor: 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.

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2016-08
• Primary Completion: 2017-01-12
• Study Completion: 2017-01-12
• Study First Submitted: 2017-06-19
• Study First Submitted QC: 2017-06-19
• Study First Posted: 2017-06-21
• Status Verified: 2017-10
• Last Update Submitted: 2017-10-31
• Last Update Posted: 2017-11-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 12

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Control	Control	Single oral intake of flavanol-free fruit-flavored non-dairy drink
Procyanidin Dimer B2 (DB2)	Procyanidin Dimer B2 (DB2)	Single oral intake of a fruit-flavored non-dairy drink containing Procyanidin Dimer B2 (DB2)
Thearubigins	Thearubigins	Single oral intake of a fruit-flavored non-dairy drink containing thearubigins
(-)-Epicatechin (EC)	(-)-Epicatechin (EC)	Single oral intake of a fruit-flavored non-dairy drink containing (-)-Epicatechin (EC)
Theaflavins	Theaflavins	Single oral intake of a fruit-flavored non-dairy drink containing a mixture of theaflavins
(-)-Epigallocatechin (EGC)	(-)-Epigallocatechin (EGC)	Single oral intake of a fruit-flavored non-dairy drink containing (-)-Epigallocatechin (EGC)
(-)-Epigallocatechin-3-O-gallate (EGCG)	(-)-Epigallocatechin-3-O-gallate (EGCG)	Single oral intake of a fruit-flavored non-dairy drink containing (-)-Epigallocatechin-3-O-gallate (EGCG)
(-)-Epicatechin-3-O-gallate (ECG)	(-)-Epicatechin-3-O-gallate (ECG)	Single oral intake of a fruit-flavored non-dairy drink containing (-)-Epicatechin-3-O-gallate (ECG)

Primary Outcome Measures

Name	Time	Method
Changes in the concentration of flavanol metabolites in plasma	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.
Changes in the concentration of flavanol metabolites in urine.	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.

Trial Locations

Locations (1)

UC Davis; 🇺🇸 Davis, California, United States