Absorption, Metabolism and Excretion of Dietary Polyphenolic Bioactives in Humans

NCT03194620 | Completed

• 1 other identifier: 907244
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

Flavanols; Cocoa Flavanols; Epicatechins; Polyphenols; Procyanidins; EGCG; EGC; ECG; Theaflavins; Thearubigins

Outcome Measures

Primary Outcomes (2)

• Changes in the concentration of flavanol metabolites in urine.

  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

  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

Study Arms (8)

Control

PLACEBO COMPARATOR

Single oral intake of flavanol-free fruit-flavored non-dairy drink

Other: Control

Theaflavins

EXPERIMENTAL

Single oral intake of a fruit-flavored non-dairy drink containing a mixture of theaflavins

Other: Theaflavins

Procyanidin Dimer B2 (DB2)

EXPERIMENTAL

Single oral intake of a fruit-flavored non-dairy drink containing Procyanidin Dimer B2 (DB2)

Other: Procyanidin Dimer B2 (DB2)

(-)-Epigallocatechin-3-O-gallate (EGCG)

EXPERIMENTAL

Single oral intake of a fruit-flavored non-dairy drink containing (-)-Epigallocatechin-3-O-gallate (EGCG)

Other: (-)-Epigallocatechin-3-O-gallate (EGCG)

(-)-Epicatechin-3-O-gallate (ECG)

EXPERIMENTAL

Single oral intake of a fruit-flavored non-dairy drink containing (-)-Epicatechin-3-O-gallate (ECG)

Other: (-)-Epicatechin-3-O-gallate (ECG)

(-)-Epicatechin (EC)

ACTIVE COMPARATOR

Single oral intake of a fruit-flavored non-dairy drink containing (-)-Epicatechin (EC)

Other: (-)-Epicatechin (EC)

(-)-Epigallocatechin (EGC)

EXPERIMENTAL

Single oral intake of a fruit-flavored non-dairy drink containing (-)-Epigallocatechin (EGC)

Other: (-)-Epigallocatechin (EGC)

Thearubigins

EXPERIMENTAL

Single oral intake of a fruit-flavored non-dairy drink containing thearubigins

Other: Thearubigins

Interventions

Thearubigins OTHER

Single oral intake of 94.9 mg of therubigins (isolated from black tea) in a flavanol-free, fruit flavored, non-dairy drink

Thearubigins

Theaflavins OTHER

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

Theaflavins

Procyanidin Dimer B2 (DB2) OTHER

Single oral intake of 120 µmol of Procyanidin Dimer B2 (DB2) (isolated from Theobroma cacao) in a flavanol-free, fruit flavored, non-dairy drink.

Procyanidin Dimer B2 (DB2)

(-)-Epigallocatechin-3-O-gallate (EGCG) OTHER

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.

(-)-Epigallocatechin-3-O-gallate (EGCG)

(-)-Epicatechin-3-O-gallate (ECG) OTHER

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.

(-)-Epicatechin-3-O-gallate (ECG)

(-)-Epicatechin (EC) OTHER

Single oral intake of 120 µmol of (-)-Epicatechin (EC) (isolated from green tea) in a flavanol-free, fruit flavored, non-dairy drink.

(-)-Epicatechin (EC)

(-)-Epigallocatechin (EGC) OTHER

Single oral intake of 120 µmol of (-)-Epigallocatechin (EGC) (isolated from green tea) in a flavanol-free, fruit flavored, non-dairy drink.

(-)-Epigallocatechin (EGC)

Control OTHER

Single oral intake of a flavanol-free, fruit flavored, non-dairy drink.

Control

Eligibility Criteria

• Age: 25 Years - 60 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of California, Davis: lead
• Mars, Inc.: collaborator

Study Sites (1)

UC Davis

Davis, California, 95616, United States

Location

Related Publications (7)

• Schroeter H, Heiss C, Spencer JP, Keen CL, Lupton JR, Schmitz HH. Recommending flavanols and procyanidins for cardiovascular health: current knowledge and future needs. Mol Aspects Med. 2010 Dec;31(6):546-57. doi: 10.1016/j.mam.2010.09.008. Epub 2010 Sep 18.

  PMID: 20854838 BACKGROUND

• Ottaviani JI, Momma TY, Kuhnle GK, Keen CL, Schroeter H. Structurally related (-)-epicatechin metabolites in humans: assessment using de novo chemically synthesized authentic standards. Free Radic Biol Med. 2012 Apr 15;52(8):1403-12. doi: 10.1016/j.freeradbiomed.2011.12.010. Epub 2011 Dec 23.

  PMID: 22240152 BACKGROUND

• Koster H, Halsema I, Scholtens E, Knippers M, Mulder GJ. Dose-dependent shifts in the sulfation and glucuronidation of phenolic compounds in the rat in vivo and in isolated hepatocytes. The role of saturation of phenolsulfotransferase. Biochem Pharmacol. 1981 Sep 15;30(18):2569-75. doi: 10.1016/0006-2952(81)90584-0. No abstract available.

  PMID: 6946775 BACKGROUND

• McCullough ML, Chevaux K, Jackson L, Preston M, Martinez G, Schmitz HH, Coletti C, Campos H, Hollenberg NK. Hypertension, the Kuna, and the epidemiology of flavanols. J Cardiovasc Pharmacol. 2006;47 Suppl 2:S103-9; discussion 119-21. doi: 10.1097/00005344-200606001-00003.

  PMID: 16794446 BACKGROUND

• Heiss C, Kleinbongard P, Dejam A, Perre S, Schroeter H, Sies H, Kelm M. Acute consumption of flavanol-rich cocoa and the reversal of endothelial dysfunction in smokers. J Am Coll Cardiol. 2005 Oct 4;46(7):1276-83. doi: 10.1016/j.jacc.2005.06.055.

  PMID: 16198843 BACKGROUND

• Del Rio D, Rodriguez-Mateos A, Spencer JP, Tognolini M, Borges G, Crozier A. Dietary (poly)phenolics in human health: structures, bioavailability, and evidence of protective effects against chronic diseases. Antioxid Redox Signal. 2013 May 10;18(14):1818-92. doi: 10.1089/ars.2012.4581. Epub 2012 Aug 27.

  PMID: 22794138 BACKGROUND

• Ottaviani JI, Kwik-Uribe C, Keen CL, Schroeter H. Intake of dietary procyanidins does not contribute to the pool of circulating flavanols in humans. Am J Clin Nutr. 2012 Apr;95(4):851-8. doi: 10.3945/ajcn.111.028340. Epub 2012 Feb 29.

  PMID: 22378733 BACKGROUND

MeSH Terms

Interventions

theaflavin; epigallocatechin gallate; epicatechin gallate; Catechin; gallocatechol

Intervention Hierarchy (Ancestors)

Chromans; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Flavonoids; Chromones; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Carl L Keen, PhD

  UC Davis

  PRINCIPAL INVESTIGATOR

• Javier I Ottaviani, PhD

  Mars, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, double-masked and cross-over dietary intervention study in healthy young adult males

Study Record Dates

• First Submitted: June 19, 2017
• First Posted: June 21, 2017
• Study Start: August 1, 2016
• Primary Completion: January 12, 2017
• Study Completion: January 12, 2017
• Last Updated: November 6, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will share

Locations

US (1)