Oral Bioavailability and Bioactivity of Prenylflavonoids From Hops

March 29, 2018 updated by: University of Hohenheim

Examination of the Bioavailability and Bioactivity of the Two Natural Food Ingredients 6-Prenylnaringenin and 8-Prenylnaringenin.

The prenylflavonoids 6-prenylnaringenin (6-PN) and 8-prenylnaringenin (8-PN) are secondary plant substances, almost exclusively found in hops (Humulus lupulus). Both compounds have known potential biological properties, but poor bioavailability due to their low oral absorption and retention. Our study followed a single dose (500 mg 6- or 8-PN), placebo controlled, randomized, double-blind, three armed crossover study design with ≥2-week washout periods. Plasma, PBMC and urine samples were collected at intervals up to 24 h after intake. Investigators investigated the safety, pharmacokinetics and impact of oral prenylflavonoids on the function of cells of the immune system.

Study Overview

Study Type

Interventional

Enrollment (Actual)

16

Phase

  • Early Phase 1

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

    • Baden-Württemberg
      • Stuttgart, Baden-Württemberg, Germany, 70599
        • University of Hohenheim
      • Tübingen, Baden-Württemberg, Germany, 72076
        • Eberhard Karls University Tuebingen

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

16 years to 43 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Healthy Volunteers with blood chemistry values within normal ranges
  • Age: 18-45 years
  • BMI: 19-25 kg/m2

Exclusion Criteria:

  • Pregnancy or lactation
  • Alcohol and/or drug abuse
  • Use of dietary supplements or any medications, except contraceptives
  • Any known malignant, metabolic and endocrine diseases
  • Previous cardiac infarction
  • Dementia
  • Participation in a clinical trial within the past 6 weeks prior to recruitment
  • Physical activity of more than 5 h/wk

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: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Capsules filled with mannitol and silicon dioxide
Experimental: 6-prenylnaringenin
500 mg 6-PN plus mannitol and silicon dioxide
Other Names:
  • 6-PN
Experimental: 8-prenylnaringenin
500 mg 8-PN plus mannitol and silicon dioxide
Other Names:
  • 8-PN

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean area under the curve (AUC) of plasma concentration vs. time of total 6-prenylnaringenin [nmol/L*h]
Time Frame: 0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose
Total 6-PN after deconjugation with beta-glucuronidase/sulphatase
0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose
Mean area under the curve (AUC) of plasma concentration vs. time of total 8-prenylnaringenin [nmol/L*h]
Time Frame: 0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose
Total trans-epsilon-viniferin after deconjugation with beta-glucuronidase/sulphatase
0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose
Mean maximum plasma concentration (Cmax) of total 6-prenylnaringenin [nmol/L]
Time Frame: 0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose
Total trans-resveratrol after deconjugation with beta-glucuronidase/sulphatase
0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose
Mean maximum plasma concentration (Cmax) of total 8-prenylnaringenin [nmol/L]
Time Frame: 0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose
Total trans-epsilon-viniferin after deconjugation with beta-glucuronidase/sulphatase
0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose
Time to reach maximum plasma concentration (Tmax) of total 6-prenylnaringenin [h]
Time Frame: 0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose
Total trans-resveratrol after deconjugation with beta-glucuronidase/sulphatase
0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose
Time to reach maximum plasma concentration (Tmax) of total 8-prenylnaringenin [h]
Time Frame: 0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose
Total trans-epsilon-viniferin after deconjugation with beta-glucuronidase/sulphatase
0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose
Cumulative urinary excretion of total 6-prenylnaringenin [nmol/g creatinine]
Time Frame: 0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose
Total trans-resveratrol after deconjugation with beta-glucuronidase/sulphatase
0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose
Cumulative urinary excretion of total 8-prenylnaringenin [nmol/g creatinine]
Time Frame: 0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose
Total trans-epsilon-viniferin after deconjugation with beta-glucuronidase/sulphatase
0, 0.5, 1, 2, 4, 6, 8 and 24 h post dose
Cell count (dead cells/ml and living cells/ml) of PBMCs after 6-PN administration
Time Frame: 0, 6, and 24 h post dose
0, 6, and 24 h post dose
Cell count (dead cells/ml and living cells/ml) of PBMCs after 8-PN administration
Time Frame: 0, 6, and 24 h post dose
0, 6, and 24 h post dose
Cell viability of PBMCs after 6-PN administration
Time Frame: 0, 6, and 24 h post dose
0, 6, and 24 h post dose
Cell viability of PBMCs after 8-PN administration
Time Frame: 0, 6, and 24 h post dose
0, 6, and 24 h post dose

Secondary Outcome Measures

Outcome Measure
Time Frame
Serum aspartate transaminase activity [U/L]
Time Frame: 0, 4, 24h post-dose
0, 4, 24h post-dose
Serum alanine transaminase activity [U/L]
Time Frame: 0, 4, 24h post-dose
0, 4, 24h post-dose
Serum gamma-glutamyl transferase activity [U/L]
Time Frame: 0, 4, 24h post-dose
0, 4, 24h post-dose
Serum alkaline phosphatase activity [U/L]
Time Frame: 0, 4, 24h post-dose
0, 4, 24h post-dose
Serum bilirubin
Time Frame: 0, 4, 24h post-dose
0, 4, 24h post-dose
Serum uric acid [mg/dL]
Time Frame: 0, 4, 24h post-dose
0, 4, 24h post-dose
Serum creatinine [mg/dL]
Time Frame: 0, 4, 24h post-dose
0, 4, 24h post-dose
Serum total cholesterol [mg/dL]
Time Frame: 0, 4, 24h post-dose
0, 4, 24h post-dose
Serum HDL cholesterol [mg/dL]
Time Frame: 0, 4, 24h post-dose
0, 4, 24h post-dose
Serum LDL cholesterol [mg/dL]
Time Frame: 0, 4, 24h post-dose
0, 4, 24h post-dose
Serum triacylglycerols [mg/dL]
Time Frame: 0, 4, 24h post-dose
0, 4, 24h post-dose
LDL/HDL cholesterol ratio
Time Frame: 0, 4, 24h post-dose
0, 4, 24h post-dose
Serum cystatin C [mg/mL]
Time Frame: 0, 4, 24h post-dose
0, 4, 24h post-dose
Glomerular filtration rate [mL/min]
Time Frame: 0, 4, 24h post-dose
0, 4, 24h post-dose
Serum glucose [mg/dL]
Time Frame: 0, 24h post-dose
0, 24h post-dose
Hemoglobin [g/dL]
Time Frame: 0, 24h post-dose
0, 24h post-dose
Mean corpuscular hemoglobin concentration [g/dL]
Time Frame: 0, 24h post-dose
0, 24h post-dose
Mean corpuscular hemoglobin [pg]
Time Frame: 0, 24h post-dose
0, 24h post-dose
Mean corpuscular volume [fL]
Time Frame: 0, 24h post-dose
0, 24h post-dose
Hematocrit [%]
Time Frame: 0, 24h post-dose
0, 24h post-dose
Erythrocytes [/pL]
Time Frame: 0, 24h post-dose
0, 24h post-dose
Thrombocytes [/nL]
Time Frame: 0, 24h post-dose
0, 24h post-dose
Leucocytes [/nL]
Time Frame: 0, 24h post-dose
0, 24h post-dose
Segmented granulocytes [%]
Time Frame: 0, 24h post-dose
0, 24h post-dose
Lymphocytes [%]
Time Frame: 0, 24h post-dose
0, 24h post-dose
Monocytes [%]
Time Frame: 0, 24h post-dose
0, 24h post-dose
Basophil granulocytes [%]
Time Frame: 0, 24h post-dose
0, 24h post-dose
Eosinophil granulocytes [%]
Time Frame: 0, 24h post-dose
0, 24h post-dose

Collaborators and Investigators

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

Collaborators

Investigators

  • Principal Investigator: Jan Frank, Prof. Dr., University of Hohenheim
  • Principal Investigator: Sascha Venturelli, Dr. med. Dr. rer. nat., Eberhard Karls University Tuebingen
  • Principal Investigator: Christian Busch, Dr. med., Eberhard Karls University Tuebingen

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

January 1, 2016

Primary Completion (Actual)

April 1, 2017

Study Completion (Actual)

December 31, 2017

Study Registration Dates

First Submitted

May 2, 2017

First Submitted That Met QC Criteria

May 3, 2017

First Posted (Actual)

May 4, 2017

Study Record Updates

Last Update Posted (Actual)

March 30, 2018

Last Update Submitted That Met QC Criteria

March 29, 2018

Last Verified

March 1, 2018

More Information

Terms related to this study

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.

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