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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
TRIPLE
Enrollment
40
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).
The control will be a placebo capsule containing 336 mg of cellulose microcrystalline, matching the investigational product appearance.
Maastricht University Medical Centre +
Maastricht, Netherlands
Exploratory outcomes - Evaluate the changes in Pyruvate dehydrogenase activation between oleuropein and placebo groups following 1 single dose
measured by western blotting
Time frame: 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
Time frame: 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.
Time frame: 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
Time frame: After 4 weeks of supplementation
Exploratory outcomes - to evaluate the changes of fatigue between oleuropein and placebo groups
measured using Biodex dynamometer
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: Chronic effect (after 36 days of supplementation)
Exploratory outcomes - to evaluate the changes of whole body respiratory exchange ratio (RER) between oleuropein and placebo groups following 1 single dose
measured the oxygen and carbon dioxide volume using indirect calorimetry with ventilated hood
Time frame: 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
measured by the analyze of oleuropein metabolites in blood
Time frame: 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
measured by the analyze glucose in blood
Time frame: 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
measured by the analyze of Insulin in blood
Time frame: 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
measured by the analyze of free fatty acid concentration (FFA, TG) in blood
Time frame: Acute effect after first product intake + chronic effect after 36 days of intake
Exploratory outcomes - to evaluate the changes of blood pressure between oleuropein and placebo groups following 1 single dose
measured using automated inflatable cuff
Time frame: Acute effect after first product intake + chronic effect after 36 days of intake
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Exploratory outcomes - to evaluate the changes of anti-inflammatory markers between oleuropein and placebo groups
measured by the analyze of anti-inflammatory markers in blood
Time frame: Chronic effect (after 29 days of supplementation)
Exploratory outcomes - to evaluate the changes of Antioxidant markers between oleuropein and placebo groups
measured by the analyze of antioxidant markers in blood
Time frame: Chronic effect (after 29 days of supplementation)
Exploratory outcomes - to evaluate the changes in glucose concentration between oleuropein and placebo groups
measured by the analyze glucose in blood
Time frame: Chronic effect (after 29 days of supplementation)
Exploratory outcomes - to evaluate the changes of insulin concentration between oleuropein and placebo groups
measured by the analyze of insulin in blood
Time frame: Chronic effect (after 29 days of supplementation)
Exploratory outcomes - to evaluate the changes of free fatty acid concentration between oleuropein and placebo groups
measured by the analyze of free fatty acid concentration (FFA, TG) in blood
Time frame: Chronic effect (after 29 days of supplementation)
Exploratory outcomes - to evaluate the changes in Mood state and quality of life between oleuropein and placebo groups
measured with the World Health Organisation quality of life questionnaire (WHOQOL-BREF) (rating 0 for 'not at all' and 5 for 'an extreme amount')
Time frame: Chronic effect (after 29 days of supplementation)
Exploratory outcomes - to evaluate the changes in Mood state and quality of life between oleuropein and placebo groups
measured with the Profile of Mood States - short-form (POMS-SF) - scale (rating 0 for 'not at all' and 4 for 'extremely')
Time frame: Chronic effect (after 29 days of supplementation)
Exploratory outcomes - to evaluate the changes in Mood state and quality of life between oleuropein and placebo groups
measured with the Quality of Life (QoL) questionnaires
Time frame: Chronic effect (after 29 days of supplementation)
Exploratory outcomes - to evaluate the changes in the fatigue perception and mood state pre/post Biodex measurement between oleuropein and placebo groups
measured with the current mood questionnaire (rating 0 for 'not at all' - 4 for 'extremely')
Time frame: Chronic effect (after 29 days of supplementation)
Exploratory outcomes - to evaluate the changes in the fatigue perception and mood state pre/post Biodex measurement between oleuropein and placebo groups
RPE visual analog scale Questionnaire - BORG scale (6 for 'no exertion - 20 for 'maximal exertion'
Time frame: Chronic effect (after 29 days of supplementation)
Exploratory outcomes to evaluate the changes in body composition between oleuropein and placebo groups
measure the whole body muscle and fat content using Magnetic resonance imaging (MRI)
Time frame: Chronic effect (after 29 days of supplementation)
Exploratory outcomes - Whole body respiratory exchange ratio - To evaluate the changes of Whole body respiratory exchange ratio (RER) between oleuropein and placebo groups
measure the oxygen and dioxygen volume using Indirect calorimetry with ventilation hood
Time frame: Chronic effect (after 36 days of supplementation)
Exploratory outcomes - To evaluate the changes of oleuropein metabolites between oleuropein and placebo groups
measure by analyzing Oleuropein metabolites in blood
Time frame: Chronic effect (after 36 days of supplementation)
Exploratory outcomes - to evaluate the changes of molecular signalling, and protein and mRNA levels of regulators of muscle metabolism between oleuropein and placebo groups
measured by analyzing RNAseq and MS-based proteomics
Time frame: Chronic effect (after 36 days of supplementation)
Exploratory outcomes - to evaluate the changes of molecular signalling, and protein and mRNA levels of regulators oleuropein and placebo groups
measured using Western Blot
Time frame: Chronic effect (after 36 days of supplementation)
Exploratory outcomes - to evaluate the changes of molecular signalling, and protein and mRNA levels of regulators oleuropein and placebo groups
measured by analyzing polymerase chain reaction
Time frame: Chronic effect (after 36 days of supplementation)
Exploratory outcomes - to evaluate the changes in Strength between oleuropein and placebo groups
measured using biodex dynanometer
Time frame: After 4 weeks of supplementation
Exploratory outcomes to evaluate the changes of strenght between oleuropein
measured using biodex dynanometer
Time frame: Chronic effect (after 29 days of supplementation)