Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04678713 |
| Other study ID # |
Variation in MFO |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
January 1, 2020 |
| Est. completion date |
September 30, 2021 |
Study information
| Verified date |
February 2024 |
| Source |
University of Copenhagen |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Fat and carbohydrate are the two main energy stores available as fuel during exercise. It is
well known that the exercise intensity and feeding status are the major factors determining
the type of fuel used during exercise. During prolonged exercise at low to moderate exercise
fat is the primary fuel being used and to improve performance studies has tried to understand
strategies to maximize muscle glycogen storage and elevate fat oxidation during exercise.
With this strategy they aim for preserving the limited muscle glycogen stores and thus
improving endurance performance. In relation to this the maximal fat oxidation (MFO: The
highest rate of fat oxidation across all exercise intensities) has been studied as increasing
the fat oxidation could decrease the depletion of the glycogen stores. Further it has
recently been shown that MFO is related to performance in endurance trained. However the MFO
has been found to vary markedly between trained individuals matched on their activity level.
It has been suggested that the diet and subsequent substrate availability during exercise
contributes independently to the variation in MFO. However, the measurements have never been
evaluated in a trained group with similar aerobic capacity and training status. Therefore,
the aim of the study is to investigate the effect of a short term fat rich or carbohydrate
rich diet on MFO in well trained men with a high vs. a low MFO. The hypothesis is that 3 days
of a fat-rich diet will increase MFO while 3 days of a Carbohydrate rich diet will decrease
MFO in both individuals with a high MFO (HiMFO) and a low MFO (LoMFO). Furthermore, it is
hypothesized that HiMFO will have a significantly higher MFO after both diets compared to
LoMFO.
Lifestyle and physiological factors have been investigated to determine the variation of the
MFO capacity. However, these factors can only explain 50% of the interindividual variability
in MFO. Despite the critical role of fat oxidation during exercise, few studies have explored
the differences in skeletal muscle characteristics between HiMFO and LoMFO. The second aim of
the study is thereby to investigate if muscle characteristics can explain the variability in
MFO within well-trained males. The hypothesis is that HiMFO will have more favorable muscle
characteristics for fat oxidation compared to LoMFO including a higher oxidative capacity,
intramuscular triacylglycerol concentration and a higher expression of key enzymes in lipid
metabolism.
Description:
A group of young, healthy and moderate to well-trained males will be recruited for the study.
The participants will be separated into 2 groups by stratified randomization consuming either
a 3 day Fat rich diet (HiFAT) or a carbohydrate rich diet (HiCHO).
When all participants have completed the study, the results will be analysed by separating
the two groups into two subgroups based on the median of the MFO
The study includes 4 visits to out laboratory.
When the participants have read, accepted and signed the plain language statement they will
be invited for a screening session in our laboratory which is the first visit. If the
participant meet the inclusion and not the exclusion criteria, they will be included in the
study and a time schedule for the next three visits will be planned. In the end of the
screening the participant will be instructed to full fill a 4-day diet dairy to analyse the
participants habitual diet.
For the second visit the participant will meet in the laboratory after an overnight fast and
has been asked to avoid alcohol and strenuous exercise 48 hours prior to the test day. The
second test starts with a visit to the toilet before a Dual-energy X-ray absorptiometry (DXA)
scan and a bioelectrical impedance scan (BIA) is performed to measure the body composition of
the participant. After 5 min. of rest, the blood pressure is measured followed by a
measurement of the hip and waist circumference. After measuring the blood pressure and body
composition the participant will perform a incremental exercise test on a cycle ergometer.
The expired air is measured by indirect calorimetry and is used to calculate the maximal fat
oxidation and maximal aerobic capacity.
As the second visit, the participant will arrive to laboratory in the morning after an
overnight fast having been asked to avoid alcohol and strenuous exercise 48 hours prior to
the test day. At the third visit a resting blood samples, fat and muscle biopsies are
collected. After 30 min. of rest the same incremental exercise test will be performed as at
visit 2 to measure the maximal fat oxidation and maximal aerobic capacity. The test is
performed twice to minimize the variation and to ensure the circumstances with the biopsies
are identical before and after the diet intervention.
At the end of the third visit, the participant will receive a high fat or isoenergetic high
carbohydrate diet to follow for the next three days. The participant will further receive an
activity watch to track his activity level during the diet intervention and he will be
instructed to exercise for one hour at 65 % of his maximal heart rate.
The fourth and last visit to the laboratory is the day after finishing the three days diet
intervention. The participant arrive to laboratory in the morning after an overnight fast
having been asked to avoid alcohol and strenuous exercise 48 hours prior to the test day. The
test day initiates with a visit to the toilet to empty the bladder and a DXA and BIA are
performed followed by a measurement of the blood pressure and the hip and waist
circumference. The participant is led to the laboratory where he has to rest for 5-10 min.
before collecting a resting blood sample and a fat and muscle biopsy. The participant has to
rest for further 30 min. before performing the incremental exercise test to measure the
maximal fat oxidation and maximal aerobic capacity.
Procedure and analysis:
Blood samples: The blood samples will be collected from the vein cubiti medialis in the
forearm. The blood samples will be analyzed using a standard lab biochemical assays to assess
metabolic risk factors and plasma metabolites and hormones.
Fat biopsy: The fat biopsies will be collected from the abdominal subcutane adipose tissue
3-5 cm. lateral from the navel. The samples will be collected by the Bergstrom biopsy
technique using a Bergstrom biopsy needle. The fat biopsy will be analysed using microscopy
and High Resolution Mitochondria Respirometry to assess the mitochondria capacity, the
inflammation of the macrophage and the size of the adipose cells. Furthermore, the expression
of proteins and enzymes important for the glucose and fat metabolism will be measured.
Muscle biopsy: The muscle biopsies will be collected from musculus vastus lateralis by the
doctor of our department using the Bergstrom biopsy technique. The muscle biopsy will be
analysed by immunofluorescence microscopy and the Western blot technique to assess muscle
characteristics (e.g muscle fibre type, capillary density and fibre type specific IMTG
content) and the expression of key proteins involved in FFA uptake, intramuscular lipolysis
and fat oxidation.
The expected outcomes This study will help us to understand the underlying muscular mechanism
explaining why substrate use is different amongst a group of similar well-trained athletes.
The study will further illuminate if individuals with a high maximal fat oxidation react
differently to a high fat or carbohydrate diet compared to individuals with a low maximal fat
oxidation.
This information will be highly relevant for coaches, federations, nutritionists and
endurance trained athletes looking to optimize nutritional and training methods to enhance
metabolic responses and ultimately improve exercise performance.
Statistical analysis:
A Pearsons correlation analyse was performed including all relevant physiological variables
regarding the primary outcome, Maximal fat oxidation to analyse the physiological differences
between the group with a high MFO and low MFO.
Furthermore a two way ANOVA with repeated measurements will be performed to analyse any
effect of the diet on MFO and to analyse if there is any differences on the effect of diet
between individuals with a high compared to low MFO. Any significant effects from the ANOVA
test will be analysed with a post hoc test to evaluate the interaction between HiMFO and
LoMFO.
The significant level is p<0.05.
General design:
The project was approved by the Science Ethical commitee of the greater region of Copenhagen
(H-20019103) the 3rd of July 2020. The protocol of the study adhered to the principles of the
Helsinki declaration.
