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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Exercise Intensity; Neuromuscular Fatigue; Skeletal Muscle Adaptations
• Intervention / Treatment: Dietary supplement: Olive leaf extract; Dietary supplement: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Lausanne, Switzerland, 1015
    • Bâtiment Synathlon, quartier UNIL-Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 38 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. 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).
2. Being aged between 18 and 40 years
3. Being healthy (The assessment will be done through a questionnaire and an interview/examination by a medical doctor if there is any doubts)
4. Being physically active, but not involved in any structured training program
5. Having stable dietary habits

Exclusion Criteria:

1. Having previous medical events that would put the participant at risk during the study
2. Ingesting caffeine on the experimental days
3. Not being currently treated for blood clotting problems
4. Taking aspirin or anti-coagulant drugs in the 48 hours preceding the experimental days in which muscle samples will be collected
5. Having allergy to xylocaine
6. Having food allergy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sprint interval training group (SIT group); 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; A capsule containing 250 mg of an olive leaf extract preparation will be swallowed with a glass of water before exercise.; Dietary supplement: Placebo; A capsule containing 336 mg of cellulose microcrystalline will be swallowed with a glass of water before exercise.
Experimental: Moderate intensity continuous training (MICT group); 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; A capsule containing 250 mg of an olive leaf extract preparation will be swallowed with a glass of water before exercise.; Dietary supplement: Placebo; A capsule containing 336 mg of cellulose microcrystalline will be swallowed with a glass of water before exercise.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Lausanne
• Collaborators: Société des Produits Nestlé (SPN)

Publications and helpful links

General Publications

• Place N, Ivarsson N, Venckunas T, Neyroud D, Brazaitis M, Cheng AJ, Ochala J, Kamandulis S, Girard S, Volungevicius G, Pauzas H, Mekideche A, Kayser B, Martinez-Redondo V, Ruas JL, Bruton J, Truffert A, Lanner JT, Skurvydas A, Westerblad H. Ryanodine receptor fragmentation and sarcoplasmic reticulum Ca2+ leak after one session of high-intensity interval exercise. Proc Natl Acad Sci U S A. 2015 Dec 15;112(50):15492-7. doi: 10.1073/pnas.1507176112. Epub 2015 Nov 2.
• Zanou N, Dridi H, Reiken S, Imamura de Lima T, Donnelly C, De Marchi U, Ferrini M, Vidal J, Sittenfeld L, Feige JN, Garcia-Roves PM, Lopez-Mejia IC, Marks AR, Auwerx J, Kayser B, Place N. Acute RyR1 Ca2+ leak enhances NADH-linked mitochondrial respiratory capacity. Nat Commun. 2021 Dec 10;12(1):7219. doi: 10.1038/s41467-021-27422-1.

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2022
• Primary Completion (Actual): December 7, 2022
• Study Completion (Actual): December 7, 2022

Study Registration Dates

• First Submitted: April 14, 2022
• First Submitted That Met QC Criteria: April 21, 2022
• First Posted (Actual): April 28, 2022

Study Record Updates

• Last Update Posted (Actual): May 10, 2023
• Last Update Submitted That Met QC Criteria: May 9, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Fatigue
• Other Study ID Numbers: 2021-00373

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No