Bioavailability of Hesperidine and Narirutin From Orange Juice to Identify Metabotypes in Hypertension (FLAVOTIP)

Study of the Bioavailability of Hesperidine and Narirutin Provided by an Orange Juice to Identify Various Metabotypes in Prehypertensive and Hypertensive Grade 1 Individuals (FLAVOTIP)

Flavonoids are polyphenolic compound mainly found in fruits and vegetables with numerous beneficial health effects as protection against cardiovascular diseases by an antihypertensive effect. The intestinal microbiota plays a key role in the metabolization of these compounds, so that differences in the composition and activity of the microbiota between individuals can generate different metabotypes. Flavonoids are found mainly in their conjugated form linked to the monosaccharide rhamnose and need to be metabolized by the intestinal bacteria, releasing the rhamnose, to be absorbed and, thus, bioactive. The bacterial enzyme responsible of rhamnose hydrolysis is α-L-rhamnosidase, whose activity can vary considerably depending on the composition of the microbiota. In fact, a great interindividual variability has been observed in the ability to absorb flavonoids, which allows to classify individuals according to the corresponding metabotype. In a previous project, the investigators confirmed the interindividual differences in the bioavailability of hesperidin and narirutin, two flavonoids naturally present in orange juice. However, the role of the intestinal microbiota in the metabolism of hesperidin and narirutin needs to be elucidated.

On this basis, the following hypothesis is presented: individuals with arterial hypertension can be classified into 3 different metabotypes that are the result of the ability to absorb hesperidin and narirutin, determined by the urinary excretion of their respective metabolites, and these metabotypes are associated with different microbiota enterotypes and with different fecal α-L-rhamnosidase activity.

Study Overview

Status

Completed

Study Type

Interventional

Enrollment (Actual)

67

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

    • Tarragona
      • Reus, Tarragona, Spain
        • Centro Tecnológico de Nutrición y Salud (Eurecat-Reus)

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Men and women over 18 years of age
  2. Systolic blood pressure ≤159 mm Hg
  3. Sign the informed consent

Exclusion Criteria:

  1. Body mass index (BMI) ≥ 35 kg / m2
  2. Glucose > 126 mg / dL
  3. Systolic blood pressure ≥ 160 mm Hg and diastolic blood pressure > 100 mm Hg or taking antihypertensive drugs
  4. LDL cholesterol > 189 mg / dL
  5. Triglycerides > 350 mg / dL
  6. Anemia (hemoglobin ≤ 13 g / dL in men and ≤ 12 g / dL in women)
  7. Tobacco addiction
  8. Consumption of medicines, antioxidants or vitamin supplements 30 days before the study
  9. Use of antibiotics during the last 30 days prior to the study
  10. Consumption of prebiotics and / or probiotics during the 30 days prior to the study
  11. Clinical history of gastrointestinal disease or presence of intestinal disorders at the time of inclusion
  12. Chronic alcoholism
  13. Monitoring a vegetarian diet
  14. Pregnant or with intent to get pregnant
  15. Being in breastfeeding period
  16. Participation in a clinical trial or nutritional intervention study, in the last 30 days.
  17. Inability to follow the study guidelines

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Orange juice rich in hesperidin and narirutin
The consumption of the orange juice will be made in a single dose of 500 ml. The juice is presented in a concentrated and frozen format, packed in opaque cans of 500 mL, for which it must be thawed and diluted with mineral water up to 1.5 L before its ingestion.
The product is a concentrated orange juice provided by the CITRUS Department of Florida (USA: www.FloridaCitrus.org).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of absorption of hesperidin and narirutin
Time Frame: After 24 hours of juice consumption

Quantification of the metabolites derived from hesperidin and narirutin in basal and 24-hour urine samples, using Liquid Chromatography coupled to Mass Spectrometry (LC-QqQ).

From the profile of metabolites detected in urine, the percentage of absorption of hesperidin and narirutin with respect to the amount ingested will be quantified to determine the metabotypes, based on the urinary excretion corresponding to each volunteer:

After 24 hours of juice consumption

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Fecal α-L-rhamnosidase activity
Time Frame: Basal
Quantification of α-L-rhamnosidase activity in fecal samples by incubation of the samples with the substrate p-nitrophenyl α-Lrhamnopyranoside and the subsequent measurement of the aborsbance to a length wavelength of 405 nM in a spectrophotometer.
Basal
Gut microbiota composition
Time Frame: Basal

Metagenomic analysis in fecal samples. The bacteria DNA will be extracted and massive sequenced by the Ion Torrent platform.

The relative abundances of the different bacterial populations will be determined in fecal samples at different taxonomic levels, and microbial diversity will be analyzed.

Basal
Enterotype classification
Time Frame: Basal

Metagenomic analysis in fecal samples. The bacteria DNA will be extracted and massive sequenced by the Ion Torrent platform.

Enterotypes will be analyzed to classify volunteers in 3 enterotypes based on their intestinal microbiota composition.

Basal
Creatinine levels
Time Frame: Basal and after 24 hours of juice consumption
Quantification of creatinine concentration in basal urine and 24 hours urine samples by a colorimetric assay.
Basal and after 24 hours of juice consumption

Collaborators and Investigators

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

Investigators

  • Principal Investigator: Rosa Solà, Dr, UTNS(Eurecat_Reus)/HUSJR. Reus, Tarragona, Spain

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.

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)

February 24, 2020

Primary Completion (Actual)

September 22, 2020

Study Completion (Actual)

September 22, 2020

Study Registration Dates

First Submitted

January 13, 2020

First Submitted That Met QC Criteria

January 15, 2020

First Posted (Actual)

January 21, 2020

Study Record Updates

Last Update Posted (Actual)

February 28, 2022

Last Update Submitted That Met QC Criteria

February 25, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FLAVOTIP

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

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.

Clinical Trials on Hypertension

Clinical Trials on Orange juice rich in hesperidin and narirutin

3
Subscribe