The primary objective of this study is to measure mitochondrial function in PBMCs from endurance-trained and untrained young females and link it to vitamin B2 status. Secondary objectives are to compare basal and exercise-stimulated mitochondrial…
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Health condition
metabolisme
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Outcome measures
Primary outcome
The main study parameters are mitochondrial function in PBMCs measured using
the Seahorse XFe96 analyser, expressed as mitochondrial oxygen consumption
(pmol O2/min), and vitamin B2 status, measured using the erythrocyte
glutathione reductase (GR) activity coefficient (EGRAC) combined with plasma
and urine vitamin B2 and derivative analysis.
Secondary outcome
Subjects will be screened for VO2max, measured using an incremental exercise
protocol on a bicycle ergometer. Sixteen endurance-trained and sixteen
untrained subjects will be included based on their VO2max. These subjects are
invited to the two study days, in a fasted state. The two study days will take
place on two consecutive days. Blood samples will be collected during both
study days to analyse mitochondrial respiration, vitamin B2 status, and markers
of mitochondrial function, metabolic health and immune function. In addition,
24-hour urine will be collected to analyse vitamin B2 status and markers of
mitochondrial function and metabolism. Muscle mitochondrial function will be
assessed in the gastrocnemius and flexor digitorum superficialis using
transient arterial occlusions and NIRS measurements. Subjects will conduct an
exercise protocol on a bicycle ergometer for 60 minutes at 70% of their VO2max.
Subjects will be asked to adhere to dietary guidelines to standardize their
intake of vitamin B2, and to record their food intake during the first study
day. Physical activity is monitored using a wearable accelerometer in the
period between the two study days.
Background summary
Extensive endurance training puts a high energy demand on the human body.
Macronutrient as well as micronutrient requirements should be met to support
the generation of energy. Mitochondria generate energy by the oxidation of
macromolecules, and vitamins and minerals are essential to support mitochondria
during substrate oxidation. Although all B-vitamins are involved in
mitochondrial function, vitamin B2 is of particular interest as it is directly
involved in energy generation and ROS production. Furthermore, in human
studies, exercise was negatively associated with vitamin B2 status and trained
individuals have been reported to have poor vitamin B2 status. Previously, we
observed compromised mitochondrial function in PBMCs from endurance-trained
individuals. We now want to address the role of vitamin B2 in endurance-trained
individuals, and its role in supporting mitochondrial PBMC function as well as
other cellular function. Since we previously demonstrated that muscle
mitochondrial recovery constants, as measured by NIRS, are excellent
non-invasive markers of mitochondrial capacity in muscle, we will use NIRS to
characterize muscle mitochondrial capacity in our participants, and study the
association with vitamin B2 status.
Study objective
The primary objective of this study is to measure mitochondrial function in
PBMCs from endurance-trained and untrained young females and link it to vitamin
B2 status. Secondary objectives are to compare basal and exercise-stimulated
mitochondrial function in PBMCs and vitamin B2 status, to understand how
exercise impacts PBMC metabolism and vitamin B2 status and to study whether
this differs between endurance-trained and untrained individuals.
Characterization of muscle mitochondrial capacity will be measured using NIRS
to study the association between vitamin B2 status and muscle mitochondrial
function. Furthermore, markers of mitochondrial and metabolic health will be
analysed to investigate the mechanistic link between mitochondrial function in
PBMCs and vitamin B2 status
Study design
Observational study
Study burden and risks
No direct health benefit for the subjects is expected. The experimental
procedures are safe, but can cause discomfort to a certain degree. The exercise
test could lead to muscle fatigue and soreness afterwards. Blood sampling can
cause local hematoma or bruising. Non-invasive measurement of mitochondrial
capacity using NIRS makes use of arterial occlusions by external pressure,
which can be painful or uncomfortable and possibly could bruise the site of the
occlusion. Slight adjustments in daily life are asked from the subjects; e.g.
the subject is asked to adhere to dietary guidelines, refrain from physical
activity and alcohol before the test days and is expected to fast overnight.
Also, the participant is asked to fill out questionnaires. A financial
compensation for the time investment of ¤75 is offered when completing the
study.
De Elst 1
Wageningen 6708 WD
NL
De Elst 1
Wageningen 6708 WD
NL
Listed location countries
Age
Inclusion criteria
* 18-28 year old female
* BMI 18.5-25 kg/m2
* VO2max * 37 mL/kg/min or VO2max * 47 mL/kg/min
Exclusion criteria
* Health concerns regarding respiratory and pulmonary diseases, for example
COPD or (exercise induced) asthma;
* (Known symptoms of) chronic diseases, for example cardiovascular disease and
cancer;
* (Known symptoms of) metabolic diseases, for example type I or II diabetes or
hyperthyroidism;
* (Known symptoms of) inborn metabolic diseases, for example
glucose-6-phosphate dehydrogenase (G6PD) deficiency;
* (Known symptoms of) hematological disorders, for example anemia or disturbed
red blood cell formation;
* Haemoglobin concentrations below 7.5 mmol/L;
* Regular smoker (defined as smoking >5 cigarettes per week);
* Lactating or pregnant;
* Following a veganistic lifestyle, i.e. excluding the consumption of animal or
animal-derived food products. Vegetarians are allowed to participate in the
study;
* Usage of hormonal contraceptive medication other than the birth control pill
Microgynon 20/30 or a generic variant containing 0.02/0.03 mg ethinylestradiol
and 0.10/0.15 mg levonorgestel. Examples include IUD contraceptives or
contraceptive rings. The use of condoms or pessaria is allowed;
* Recent use (within four months) of supplements with suggestive training
effects, for example creatine phosphate, EPO or anabolic steroid;
* Recent daily usage (within four weeks) of supplements containing vitamin B2
(including multivitamin supplements) and usage of vitamin B2 supplements during
the study;
* Usage of recreational drugs, for example marihuana, amphetamines and cocaine
during the study (starting after first screening day);
* Suffers from (sport) injury that hampers maximal exercise performance;
* Blood donation during the previous 2 months or during the course of study;
* Current participation in other clinical trials;
* Not subscribed to a general practice (GP) practice;
* Employed or undertaking a thesis or internship at the department of Human and
Animal Physiology.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
Register | ID |
---|---|
CCMO | NL70136.081.19 |
Other | Wordt nog toegekend door het Nederlands Trial Register |
OMON | NL-OMON24874 |