Metabotypes in the Urinary Excretion of Flavan-3-ol Metabolites: "Metanols"

NCT04124016 | Suspended

• 1 other identifier: 796/2018/SPER/UNIPR
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Flavan-3-ols are the main source of flavonoids in Western diets. They are characteristic compounds of tea, cocoa, wine, apple, pears, etc. In plant-based foods, they occur as simple monomers or as oligomers and polymers of up to 50 units (also known as proanthocyanidins or condensed tannins). When ingested, both monomeric and high molecular weight flavan-3-ols are poorly absorbed and metabolized in the first gastrointestinal tract, reaching the colon and becoming a suitable substrate for the local microbiota. These compounds undergo an extensive microbial metabolism leading to the formation of hydroxyphenyl-γ- valerolactones (PVLs), which are then absorbed by colonocytes before reaching the liver and being converted into phase II conjugated metabolites. Since the microbiota composition varies among individuals, it results in differences in the production of PVLs and, consequently, the health effects of flavan-3-ols might change at an individual level. Another factor of variability might be due to a different asset in the fermentation of indigestible dietary carbohydrates, which are known to modify colonic pH through the production of short-chain fatty acids and may result in different profiles of gas production (i.e. hydrogen and methane), possibly affecting the bioconversion of flavan-3-ols as well. Nevertheless, these multiple variabilities are poorly understood to date.

Conditions

Diet Modification

Keywords

flavan-3-ol; phenyl-y-valerolactones; catechins; metabotype; gas production; gut microbiota

Outcome Measures

Primary Outcomes (1)

• Assessing the formation of urinary metabotypes of flavan-3-ol colonic metabolites

  Assessing the variability of the area under the curve of the urinary concentration of some phenolic metabolites ( tri- and di-hydroxyphenyl-γ-valerolactones and 3-hydroxyphenylpropionic acids (umol)) after consumption of 3 different sources of flavan-3-ols by using data-driven clustering.

  AUC for 24 hours (sum of 0-180; 180-360; 360-540; 540-720; 720-1440 minutes)

Secondary Outcomes (7)

• Evolution over the time of the metabolites of flavan-3-ols in urine samples

  AUC for 48 hours (sum of 0-180; 180-360; 360-540; 540-720; 720-1440; 1440-2160; 2160-2880; 2880 minutes)

• Identification of Firmicutes, bacteroidetes and Archea in faecal samples of participants

  Baseline

• Evaluation of inter-individual differences on breath-gases production (hydrogen and methane) on alveolar air samples

  AUC for 12 hours; (sum of 60; 120; 180; 240; 300; 360; 420; 480; 540; 600; 660; 720 minutes)

• Correlations between colonic fermentation, gas production and microbiota composition and metabotypes

  24 hours

• In vitro variation of gases production by fermentable dietary fibre in presence of polyphenols using faecal starters

  Baseline

Study Arms (4)

Inulin

EXPERIMENTAL

Inulin\_ extract of chicory fermentable fiber

Dietary Supplement: Inulin

green tea extract

EXPERIMENTAL

green tea extract\_rich in tri-hydroxylated flavan-3-ol monomers (1 mmol of PVL precursor)

Dietary Supplement: green tea extract

grape seed

EXPERIMENTAL

grape seed extract - rich in di-hydroxylated flavan-3-ol monomers (1 mmol of PVL precursors)

Dietary Supplement: grape seed

grape seed exctract

EXPERIMENTAL

grape seed extract - rich in di-hydroxylated flavan-3-ol oligomers (1 mmol of PVL precursors)

Dietary Supplement: grape seed extract

Interventions

Inulin DIETARY_SUPPLEMENT

Powder of inulin fractions dissolved into 250 ml of water

Inulin

green tea extract DIETARY_SUPPLEMENT

Powder of green tea extract dissolved into 200 ml of water

green tea extract

grape seed DIETARY_SUPPLEMENT

Powder of grape seed extract (rich in di-hydroxylated flavan-3-ol monomers) dissolved into 200 ml of water

grape seed

grape seed extract DIETARY_SUPPLEMENT

Powder of grape seed extract (rich in di-hydroxylated flavan-3-ol oligomers) dissolved into 200 ml of water

grape seed exctract

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult
• Both genders
• Healthy
• BMI \> 18.5
• BMI \< 30

You may not qualify if:

• Metabolic disorder or surgeries of liver, kidney or gastrointestinal tract
• Immunodeficiency
• Food intolerance or allergies
• Regular consumption of medication
• Antibiotic therapy within the last 3 months
• Use of food supplements, including pro- and prebiotics
• Intense physical activity (PAL ≥ 2.10)
• Pregnancy
• Lactation

Sponsors & Collaborators

• University of Parma: lead
• Azienda Ospedaliero-Universitaria di Parma: collaborator

Study Sites (1)

University of Parma

Parma, 43125, Italy

Location

MeSH Terms

Interventions

Inulin; Tea; Grape Seed Extract

Intervention Hierarchy (Ancestors)

Starch; Glucans; Biopolymers; Polymers; Macromolecular Substances; Dietary Carbohydrates; Carbohydrates; Fructans; Polysaccharides; Plant Preparations; Biological Products; Complex Mixtures; Beverages; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Plant Extracts; Pharmaceutical Preparations

Study Officials

• Furio FB Brighenti, Professor

  University of Parma

  PRINCIPAL INVESTIGATOR

• Daniele DR Del Rio, Professor

  University of Parma

  STUDY DIRECTOR

• Pedro Miguel PM Mena Parreño, Ph.D.

  University of Parma

  STUDY DIRECTOR

• Rossella RD Dodi, M. Sc.

  University of Parma

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: single-dose, partially randomized, cross over design with 4 consecutive treatments

Study Record Dates

• First Submitted: September 3, 2019
• First Posted: October 11, 2019
• Study Start: September 2, 2019
• Primary Completion: February 1, 2022
• Study Completion: December 27, 2022
• Last Updated: April 30, 2021

Record last verified: 2021-04

Locations

IT (1)