Combined Effect of Exercise Intensity With Nutritional Supplementation on Skeletal Muscle Function

Study Overview
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Brief Summary
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The main objective of this study is to determine the effectiveness of a nutritional intervention (olive leaf extract) combined with a specific training session (MICT or SIT) on PDH activation (as well as other protein expressions) and exercise-induced muscle fatigue.

Detailed Description
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Sprint interval training (SIT) is a form of interval training characterised by short bursts of intense exercise interspersed with rest periods. SIT is as, or more, effective than moderate intensity continuous training (MICT) for systemic and metabolic adaptations of muscles, despite a lower workload and shorter duration. However, the mechanisms underlying the metabolic response to SIT versus MICT are poorly understood. Our recent work (Zanou et al. 2021) suggests that increased pyruvate dehydrogenase (PDH) activity may explain why a SIT session led to greater changes in proteins involved in mitochondrial respiration compared to a MICT session. Recently, it was found that a natural and commercially available compound based on olive leaf extract could stimulate resting mitochondrial bioenergetics by activating the mitochondrial calcium uniporter (MCU), which is involved in calcium transport across the mitochondrial membrane, directly controlling PDH activity. The main objective of this study is to determine the effectiveness of an acute nutritional intervention (olive leaf extract) combined with a specific training session (MICT or SIT) on PDH activation (as well as other protein expressions) and exercise-induced muscle fatigue. Participants will be allocated to either a SIT (6 x 30 s all out sprints) or a MICT (1h at 50% maximal aerobic power) group and asked to come to the laboratory for five visits including one familiarization session with a triangular test for maximal aerobic power determination, the first experimental session during which they will realize the exercise with the product or a placebo and a session 24h after to assess skeletal muscle adaptations. Then after a 3 week wash-out period, they report to the laboratory for the fourth and fifth session, identical to the second and third sessions but with the other intervention (product or placebo). Muscle microbiopsies will be collected from the vastus lateralis muscle before, immediately after and 24 hours after exercise (MICT or SIT), while knee extensor neuromuscular function will be assessed at the same time points using voluntary and electrically-evoked contractions.

Official Title
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Combined Effect of Exercise Intensity With Nutritional Supplementation on Skeletal Muscle Function

Conditions
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Healthy Volunteers, Exercise Intensity, Neuromuscular Fatigue, Skeletal Muscle Adaptations

Intervention / Treatment
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* Dietary Supplement: Olive leaf extract
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Being male (including females would necessitate increasing the number of included participants to consider sex as a variable which would burden the project too much). Being aged between 18 and 40 years Being healthy (The assessment will be done through a questionnaire and an interview/examination by a medical doctor if there is any doubts) Being physically active, but not involved in any structured training program Having stable dietary habits Exclusion Criteria: Having previous medical events that would put the participant at risk during the study Ingesting caffeine on the experimental days Not being currently treated for blood clotting problems Taking aspirin or anti-coagulant drugs in the 48 hours preceding the experimental days in which muscle samples will be collected Having allergy to xylocaine Having food allergy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: The design is a placebo-controlled, double blind, cross-over two-arm study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sprint interval training group (SIT group)<br>The model of sprint interval training (SIT) consists of six 30 s all-out cycling bouts on a cycle ergometer, with 4 min rests between tests. | Dietary Supplement: Olive leaf extract<br>* A capsule containing 250 mg of an olive leaf extract preparation will be swallowed with a glass of water before exercise.<br>Dietary Supplement: Placebo<br>* A capsule containing 336 mg of cellulose microcrystalline will be swallowed with a glass of water before exercise.<br>|
| Experimental: Moderate intensity continuous training (MICT group)<br>The moderate intensity continuous training (MICT) consists of 1h cycling on a cycle ergometer at 50% of the maximal aerobic power output | Dietary Supplement: Olive leaf extract<br>* A capsule containing 250 mg of an olive leaf extract preparation will be swallowed with a glass of water before exercise.<br>Dietary Supplement: Placebo<br>* A capsule containing 336 mg of cellulose microcrystalline will be swallowed with a glass of water before exercise.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PDH dephosphorylation | protein involved in skeletal muscle metabolism | before, immediately after and 24 hours after exercise completion | 
| expression of OXPHOS proteins | proteins used as markers of oxidative phosphorylation complexes | before, immediately after and 24 hours after exercise completion | 
| expression of MCU protein | protein involved in the transport of Ca2+ in the mitochondria | before, immediately after and 24 hours after exercise completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal voluntary contraction force | Maximal force of the knee extensor muscles | before, immediately after and 24 hours after exercise completion | 
| Voluntary activation level | overall index of central fatigue induced by exercise | before, immediately after and 24 hours after exercise completion | 
| Peak doublet evoked at 100 Hz | overall index of peripheral fatigue induced by exercise | before, immediately after and 24 hours after exercise completion | 
| M-wave amplitude | index of neuromuscular excitability | before, immediately after and 24 hours after exercise completion |