Oral Bioavailability of the Phenolic Compounds in a Melissa Supplement (BIOLEMON)

June 13, 2025 updated by: Fytexia

Evaluation of Oral Bioavailability of the Phenolic Compounds in a Melissa Supplement: Double-blind, Randomized, Crossover Study

The objective of this study is to identify phenolic compound biomarkers of the intake of a mixture of Melissa officinalis extract, acerola extract and vitamin B5. This will be done through the study of their bioavailability and nutrikinetics by measuring their plasma concentrations and urinary excretion over 24h by means of high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). The study follows a cross-over, double-blind, randomized and placebo control design on 10 healthy subjects

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
10

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Spain
    • Tarragona
      • Reus, Tarragona, Spain, 43204
        • Eurecat

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Men and women between 18 and 60 years old.
  • Agree to follow the dietary and exercise guidelines of the study.
  • Sign the informed consent form.
  • Be able to read, write, and speak Spanish and/or Catalan.

Exclusion Criteria:

  • Body Mass Index (BMI) <18.5 kg/m² or ≥30 kg/m².
  • Presence of intolerances or allergies related to polyphenols or any of the components of the products evaluated, such as acerola, maltodextrin, or Melissa officinalis.
  • Use of medication that could affect the study results, including antibiotics, glucocorticoids, steroids, antidepressants (especially selective serotonin reuptake inhibitors (SSRIs), medications used to control sleep or stress, antipsychotics, anticonvulsants, oral contraceptives, beta-blockers, benzodiazepines, and antihypertensives.
  • Regular consumption herbal or plant-based supplements. Participants who take multivitamin supplements may still participate in the study, provided they agree to stop taking them for 48 hours before and on the day of the intervention.
  • Regular consumption of melatonin supplements. Participants who occasionally take melatonin may be included if they have had at least a one-week washout period since the last dose.
  • Presence of disrupted sleep cycle or irregular sleep routines, such as shift workers (night or rotating shifts), or due to external factors such as recent or upcoming travel across time zones, or co-sleeping with a newborn/baby that disrupts sleep.
  • Report self-perceived psychological stress, meaning they answer "yes" to the question: "Do you consider yourself to be severely stressed?"
  • Self-reported trouble sleeping and/or falling asleep.
  • To be diagnosed with anemia.
  • Active smoker or have quit smoking less than 6 months ago.
  • Consumption of alcoholic beverages: Men: 4 or more Standard Drink Units (SDUs)* daily or 28 SDUs weekly; Women: 2 or more SDUs daily or 17 SDUs weekly.
  • Presence of liver, kidney, or gastrointestinal disease that may affect compound absorption and/or study results, such as: celiac disease, Crohn's disease, chronic kidney disease, active cancer in any digestive or renal organ, or hepatitis.
  • Previous blood extraction and/or donation: ≥200 ml within 1 month prior to study inclusion, or ≥400 ml within 3 months prior to study inclusion.
  • Have lost 3 kg or more in the past 3 months.
  • Pregnant or planning to become pregnant.
  • Currently breastfeeding.
  • Unable to comply with the study protocol.
  • Currently participating or have participated in a nutritional intervention study involving nutraceuticals or pharmaceuticals within the 30 days prior to inclusion in this study.
  • Deemed unsuitable to participate in the study according to the judgment of the evaluator conducting the pre-selection.

One SDU is defined as the average alcohol content of a standard drink in terms of alcohol strength and volume. One SDU is approximately 10 grams of alcohol, which equals:1 glass of wine (120 ml), 1 beer (330 ml), 1 small liquor (25 ml); 2 SDUs equal: 1 glass of cognac or liqueur (55 ml),1 whisky (70 ml),1 mixed drink (75 ml).

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: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
This arm receives 400 mg maltodextrin
Dietary supplement: Placebo
Intake of 400 mg placebo (maltodextrin; encapsulated) in the morning (09:00)
Experimental: M_ML
This arm receives 400 mg of M_ML. M_ML is a mixture of a polyphenol-rich Melissa officinalis extract, an acerola extract and vitamin B5.
Dietary supplement: M_ML
Intake of 400 mg M_ML (encapsulated) in the morning (09:00)
Dietary supplement: M_ML
Intake of 400 mg M_ML (encapsulated) in the evening (19:00)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Changes in plasma concentrations of phenolic metabolites after acute ingestion of the supplement/placebo
Time Frame: At baseline and at 0.5 hour, 1 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, and 24 hour after treatment intake.
Plasma samples will be collected in baseline before supplement/placebo intake (0h) and up to 24h according to the time frame. Concentrations will be analyzed using liquid chromatography-time of light-mass spectometry (LC-qToF-MS). Results will be reported in nanomolar (nM).
At baseline and at 0.5 hour, 1 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, and 24 hour after treatment intake.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in plasma area under the curve (AUC) of phenolic metabolites after acute ingestion of the supplement/placebo
Time Frame: At baseline and at 0.5 hour, 1 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, and 24 hour after treatment intake.
Plasma samples will be collected in baseline before supplement/placebo intake (0h) and up to 24h according to the time frame. Concentrations will be analyzed using LC-qToF-MS.
At baseline and at 0.5 hour, 1 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, and 24 hour after treatment intake.
Change in plasma maximal concentration (Cmax) of phenolic metabolites after acute ingestion of the supplement/placebo
Time Frame: At baseline and at 0.5 hour, 1 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, and 24 hour after treatment intake.
Plasma samples will be collected in baseline before supplement/placebo intake (0h) and up to 24h according to the time frame. Concentrations will be analyzed using LC-qToF-MS.
At baseline and at 0.5 hour, 1 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, and 24 hour after treatment intake.
Change in plasma time to reach maximal concentration (Tmax) of phenolic metabolites after acute ingestion of the supplement/placebo
Time Frame: At baseline and at 0.5 hour, 1 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, and 24 hour after treatment intake.
Plasma samples will be collected in baseline before supplement/placebo intake (0h) and up to 24h according to the time frame. Concentrations will be analyzed using LC-qToF-MS.
At baseline and at 0.5 hour, 1 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, and 24 hour after treatment intake.
Change in plasma half-life (T1/2) of phenolic metabolites after acute ingestion of the supplement/placebo
Time Frame: At baseline and at 0.5 hour, 1 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, and 24 hour after treatment intake.
Plasma samples will be collected in baseline before supplement/placebo intake (0h) and up to 24h according to the time frame. Concentrations will be analyzed using LC-qToF-MS.
At baseline and at 0.5 hour, 1 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, and 24 hour after treatment intake.
Changes in 24h cumulative urinary excretion of phenolic metabolites after acute ingestion of the supplement/placebo
Time Frame: At baseline and at 3 hour, 6 hour, 10 hour and 24 hour after treatment intake.
Urine samples will be collected in baseline before supplement/placebo intake (0h) and up to 24h according to the time frame. Concentrations will be analyzed using LC-qToF-MS, and transformed to total excretion through measured excreted urinary volume.
At baseline and at 3 hour, 6 hour, 10 hour and 24 hour after treatment intake.
Changes in serum cortisol after acute ingestion of the supplement/placebo
Time Frame: At baseline and at 30.5 hour, 1 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, and 24 hour after treatment intake.
Serum samples will be collected in baseline before supplement/placebo intake (0h) and up to 24h according to the time frame. Concentrations will be analyzed using ECLIA (electrochemiluminescence immunoassay)
At baseline and at 30.5 hour, 1 hour, 2 hour, 3 hour, 4 hour, 6 hour, 8 hour, 10 hour, and 24 hour after treatment intake.
Changes in 24h cumulative urinary excretion of melatonin after acute ingestion of the supplement/placebo
Time Frame: At baseline and at 3 hour, 6 hour, 10 hour and 24 hour after treatment intake.
Urine samples will be collected in baseline before supplement/placebo intake (0h) and up to 24h according to the time frame. Concentrations will be analyzed using LC-qToF-MS, and transformed to total excretion through measured excreted urinary volume.
At baseline and at 3 hour, 6 hour, 10 hour and 24 hour after treatment intake.
Changes in 24h cumulative urinary excretion of 6-SMT (6-Sulfatoxymelatonin) after acute ingestion of the supplement/placebo
Time Frame: At baseline and at 3, 6, 10 and 24h after treatment intake.
Urine samples will be collected in baseline before supplement/placebo intake (0h) and up to 24h according to the time frame. Concentrations will be analyzed using LC-qToF-MS, and transformed to total excretion through measured excreted urinary volume.
At baseline and at 3, 6, 10 and 24h after treatment intake.
Changes in 24h cumulative urinary excretion of AFMK (N1-acetyl-N2-formyl-5-methoxykynuramine) after acute ingestion of the supplement/placebo
Time Frame: At baseline and at 3 hour, 6 hour, 10 hour and 24 hour after treatment intake.
Urine samples will be collected in baseline before supplement/placebo intake (0h) and up to 24h according to the time frame. Concentrations will be analyzed using LC-qToF-MS, and transformed to total excretion through measured excreted urinary volume.
At baseline and at 3 hour, 6 hour, 10 hour and 24 hour after treatment intake.
Changes in 24h cumulative urinary excretion of AMK (N1-acetyl-5-methoxykynuramine) after acute ingestion of the supplement/placebo
Time Frame: At baseline and at 3 hour, 6 hour, 10 hour and 24 hour after treatment intake.
Urine samples will be collected in baseline before supplement/placebo intake (0h) and up to 24h according to the time frame. Concentrations will be analyzed using LC-qToF-MS, and transformed to total excretion through measured excreted urinary volume.
At baseline and at 3 hour, 6 hour, 10 hour and 24 hour after treatment intake.
Changes in 24h cumulative urinary excretion of cortisol after acute ingestion of the supplement/placebo
Time Frame: At baseline and at 3 hour, 6 hour, 10 hour and 24 hour after treatment intake.
Urine samples will be collected in baseline before supplement/placebo intake (0h) and up to 24h according to the time frame. Concentrations will be analyzed using LC-qToF-MS, and transformed to total excretion through measured excreted urinary volume.
At baseline and at 3 hour, 6 hour, 10 hour and 24 hour after treatment intake.
Changes in 24h cumulative urinary excretion of cortisone after acute ingestion of the supplement/placebo
Time Frame: At baseline and at 3 hour, 6 hour, 10 hour and 24 hour after treatment intake.
Urine samples will be collected in baseline before supplement/placebo intake (0h) and up to 24h according to the time frame. Concentrations will be analyzed using LC-qToF-MS, and transformed to total excretion through measured excreted urinary volume.
At baseline and at 3 hour, 6 hour, 10 hour and 24 hour after treatment intake.
Changes in 24h cumulative urinary excretion of tetrahydrocortisol after acute ingestion of the supplement/placebo
Time Frame: At baseline and at 3 hour, 6 hour, 10 hour and 24 hour after treatment intake.
Urine samples will be collected in baseline before supplement/placebo intake (0h) and up to 24h according to the time frame. Concentrations will be analyzed using LC-qToF-MS, and transformed to total excretion through measured excreted urinary volume.
At baseline and at 3 hour, 6 hour, 10 hour and 24 hour after treatment intake.
Changes in 24h cumulative urinary excretion of allo-tetrahydrocortisol after acute ingestion of the supplement/placebo
Time Frame: At baseline and at 3 hour, 6 hour, 10 hour and 24 hour after treatment intake.
Urine samples will be collected in baseline before supplement/placebo intake (0h) and up to 24h according to the time frame. Concentrations will be analyzed using LC-qToF-MS, and transformed to total excretion through measured excreted urinary volume.
At baseline and at 3 hour, 6 hour, 10 hour and 24 hour after treatment intake.
Changes in 24h cumulative urinary excretion of 5-alfa-dihydrocortisol after acute ingestion of the supplement/placebo
Time Frame: At baseline and at 3 hour, 6 hour, 10 hour and 24 hour after treatment intake.
Urine samples will be collected in baseline before supplement/placebo intake (0h) and up to 24h according to the time frame. Concentrations will be analyzed using LC-qToF-MS, and transformed to total excretion through measured excreted urinary volume.
At baseline and at 3 hour, 6 hour, 10 hour and 24 hour after treatment intake.
Changes in 24h cumulative urinary excretion of 11-oxo-cortisol after acute ingestion of the supplement/placebo
Time Frame: At baseline and at 3 hour, 6 hour, 10 hour and 24 hour after treatment intake.
Urine samples will be collected in baseline before supplement/placebo intake (0h) and up to 24h according to the time frame. Concentrations will be analyzed using LC-qToF-MS, and transformed to total excretion through measured excreted urinary volume.
At baseline and at 3 hour, 6 hour, 10 hour and 24 hour after treatment intake.
Changes in 24h cumulative urinary excretion of 11-oxo-corticosterone after acute ingestion of the supplement/placebo
Time Frame: At baseline and at 3 hour, 6 hour, 10 hour and 24 hour after treatment intake.
Urine samples will be collected in baseline before supplement/placebo intake (0h) and up to 24h according to the time frame. Concentrations will be analyzed using LC-qToF-MS, and transformed to total excretion through measured excreted urinary volume.
At baseline and at 3 hour, 6 hour, 10 hour and 24 hour after treatment intake.

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fytexia

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Antoni Caimari Palou, PhD, Fundació Eurecat

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 30, 2025

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 12, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 12, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 18, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 25, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 29, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 15, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 13, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2025

More Information

Terms related to this study

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • BIOLEMON

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.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings