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.

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.

One box containing the product and one containing the placebo will be labeled A or B. The code will be kept in a sealed envelope which will be revealed only at the end of the study or in case of an adverse event.

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.

The moderate intensity continuous training (MICT) consists of 1h cycling on a cycle ergometer at 50% of the maximal aerobic power output

A capsule containing 250 mg of an olive leaf extract preparation will be swallowed with a glass of water before exercise.

A capsule containing 336 mg of cellulose microcrystalline will be swallowed with a glass of water before exercise.

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

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.