Oleuropein and Muscle Energy Metabolism

NCT05217433 | Completed

• 1 other identifier: 20.22.NRC
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Preclinical studies performed at Nestlé Research (NR) identified oleuropein as a novel activator of mitochondrial calcium import. This potentiated mitochondrial calcium uptake resulted in decreased phosphorylation of the enzyme pyruvate dehydrogenase (PDH), which is linked to its activation as a rate limiting enzyme for mitochondrial oxidation, as well as increasing mitochondrial oxygen consumption, resulting ultimately in decreases in muscle fatigue. In addition, NR demonstrated that during aging, mitochondrial calcium and oxygen consumption rates are decreased in isolated skeletal muscle fibers. The next step in the evidence development is to demonstrate efficacy of oleuropein for improved muscle energy and decreased physical fatigue in a healthy aging population.

Conditions

Muscular Fatigue

Keywords

Skeletal muscle energy and fatigue

Outcome Measures

Primary Outcomes (8)

• Exploratory outcomes - Evaluate the changes in Pyruvate dehydrogenase activation between oleuropein and placebo groups following 1 single dose

  measured by western blotting

  Chronic effect after 36 days of intake

• Exploratory outcomes - Evaluate the changes in Pyruvate dehydrogenase activation between oleuropein and placebo groups following 1 single dose

  measured by biochemical assay analysis

  Acute effect after first product intake + chronic effect after 36 days of intake

• Exploratory outcomes - to evaluate the changes Mitocondrial respiration between oleuropein and placebo groups following 1 single dose

  measured the rates of oxygen consumption (respiration or JO2) using Oroboros Oxygraph 2K systems with physiological ADP concentrations using permeabilized muscle fibres.

  Acute effect after first product intake + chronic effect after 36 days of intake

• Exploratory outcomes- to evaluate the changes of fatigue between oleuropein and placebo groups following 1 single dose

  measured using Biodex dynamometer

  After 4 weeks of supplementation

• Exploratory outcomes - to evaluate the changes of fatigue between oleuropein and placebo groups

  measured using Biodex dynamometer

  Chronic effect (after 29 days of supplementation)

• Exploratory outcomes - to evaluate the changes of Pyruvate dehydrogenase activation between oleuropein and placebo groups

  measured by western blotting

  Chronic effect (after 36 days of supplementation)

• Exploratory outcomes - to evaluate the changes of Pyruvate dehydrogenase activation between oleuropein and placebo groups

  measured by biochemical assay analysis

  Chronic effect (after 36 days of supplementation)

• Exploratory outcomes - To evaluate the changes of Mitochondrial respiration between oleuropein and placebo groups

  measured the rates of oxygen consumption (respiration or JO2) using Oroboros Oxygraph 2K systems with physiological ADP concentrations using permeabilized muscle fibres.

  Chronic effect (after 36 days of supplementation)

Secondary Outcomes (24)

• Exploratory outcomes - to evaluate the changes of whole body respiratory exchange ratio (RER) between oleuropein and placebo groups following 1 single dose

  Acute effect after first product intake+ chronic effect after 36 days of intake

• Exploratory outcomes - to evaluate the changes of oleuropein metabolites between oleuropein and placebo groups following 1 single dose

  Acute effect after first product intake + chronic effect after 36 days of intake

• Exploratory outcomes - to evaluate the changes of glucose concentration between oleuropein and placebo groups following 1 single dose

  Acute effect after first product intake + chronic effect after 36 days of intake

• Exploratory outcomes - to evaluate the changes Blood glucose, insulin, free fatty acid concentrations -between oleuropein and placebo groups following 1 single dose

  Acute effect after first product intake + chronic effect after 36 days of intake

• Exploratory outcomes - to evaluate the changes of free fatty acid concentration between oleuropein and placebo groups following 1 single dose

  Acute effect after first product intake + chronic effect after 36 days of intake

Study Arms (2)

Investigational product

EXPERIMENTAL

The investigational product is a capsule containing 100mg of the active ingredient oleuropein and will be provided once daily in the form of a 250mg olive leaf extract (i.e. 100mg of oleuropein per day) product for the duration of the intervention period (36 days).

Other: Olive leaf extract

Control arm

PLACEBO COMPARATOR

The control will be a placebo capsule containing 336 mg of cellulose microcrystalline, matching the investigational product appearance.

Other: Placebo

Interventions

Olive leaf extract OTHER

The investigational product is a capsule containing 100mg of the active ingredient oleuropein and will be provided once daily in the form of a 250mg olive leaf extract (i.e. 100mg of oleuropein per day) product for the duration of the intervention period (36 days).

Investigational product

Placebo OTHER

The control will be a placebo capsule containing 336 mg of cellulose microcrystalline, matching the investigational product appearance.

Control arm

Eligibility Criteria

• Age: 50 Years - 70 Years
• Gender Eligibility Details: 1. Male 2. 50 to 70 years old 3. BMI 18.5-29.9 kg/m2 4. Healthy as per medical history and investigator's/ physician's judgement 5. Having given informed consent
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male
• to 70 years old
• BMI 18.5-29.9 kg/m2
• Healthy as per medical history and investigator's/ physician's judgement
• Having given informed consent

You may not qualify if:

• Allergy/intolerance to the study product
• \>5% body mass change in the previous 3 months
• HbA1c ≥ 6.5%
• Blood pressure \>140/90 mmHg
• Participating in a structured (progressive) exercise program
• Smoking
• Diagnosed acute or chronic medical conditions that, in the opinion of the investigator, could impact study outcomes
• Diagnosed musculoskeletal disorders
• Chronic use of gastric acid suppressing medication
• Unauthorized concomitant medications such as calcium antagonists (e.g. valproate), oral corticosteroids, anything that will prevent subjects from safely completing the study according to the investigator or medications / drugs known interfering with the expected mechanism of action of IP or to affect the outcome parameters
• Alcohol (intake higher than 3 servings per day. One serving is 0.4 dl of alcohol, 1 dl of wine, or 3 dl of beer) or drug abuse
• Overly imbalanced or restrictive diet (e.g. hyperproteic, vegan, ketogenic, etc.)
• Subjects not willing and/or not able to comply with scheduled visits and the requirements of the study protocol
• Any implants that would be a contra-indication for performing an MRI scan.
• Participation in another study at the same time

Sponsors & Collaborators

• Société des Produits Nestlé (SPN): lead
• Maastricht University Medical Center: collaborator

Study Sites (1)

Maastricht University Medical Centre +

Maastricht, Netherlands

Location

Related Publications (1)

• Pinckaers PJ, Petrick HL, Horstman AM, Moreno-Asso A, De Marchi U, Hendriks FK, Kuin LM, Fuchs CJ, Grathwohl D, Verdijk LB, Zorenc AH, Senden JM, Migliavacca E, Metairon S, Poquet L, Morin-Rivron D, Karagounis LG, Holloway GP, Feige JN, van Loon LJ. Oleuropein Supplementation Increases Resting Skeletal Muscle Fractional Pyruvate Dehydrogenase Activity but Does Not Influence Whole-Body Metabolism: A Randomized, Double-Blind, and Placebo-Controlled Trial in Healthy, Older Males. J Nutr. 2025 May;155(5):1373-1386. doi: 10.1016/j.tjnut.2025.02.015. Epub 2025 Feb 22.

  PMID: 39993475 DERIVED

MeSH Terms

Conditions

Fatigue

Interventions

olive leaf extract

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Luc van Loon

  Maastricht University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a single-centre, double-blind, placebo controlled, randomised 2-arms parallel group study.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a single-centre, double-blind, placebo controlled, randomised 2-arms parallel group study.

Study Record Dates

• First Submitted: November 25, 2021
• First Posted: February 1, 2022
• Study Start: November 4, 2021
• Primary Completion: March 10, 2023
• Study Completion: March 10, 2023
• Last Updated: March 17, 2023

Record last verified: 2023-03

Locations

NL (1)