The Effect of Butanediol Ingestion on Skeletal Muscle Angiogenesis in Hypoxia

The Acute Effect of (R)-1,3-butanediol Ingestion on Post-exercise Skeletal Muscle Angiogenesis in Healthy Adults Under Normoxic and Hypoxic Conditions.

This study specifically aims to elucidate the effects of intermittent exogenous ketosis (IEK) as well as hypoxia on muscular pro-angiogenic factors- after a 60-min HIIT bout in normoxia. Moreover, blood and muscle oxygenation status, as well as peripheral blood flow and cognitive function will be assessed.

After an exercise bout, angiogenesis is incredibly important in the recovery process as an increased number of capillaries enables higher metabolite transport to and from the working muscle. Often, a training strategy consists of living-high (sleeping at -stimulated- altitude) and training low (training at sea level). A decreased oxygen availability, also known as hypoxia, however poses an additional stress on the human body, potentially compromising the overall training efficiency. Ketones are recently found to increase angiogenesis in response to overload training (increased skeletal muscle capillarization and VEGF content) and to increase serum EPO concentrations. Therefore, the investigators want to evaluate the isolated and interactive effects of both ketones and hypoxia on post-exercise recovery and factors implicated in skeletal muscle angiogenesis, after training in normoxia. Moreover, a performance test will be performed after 7h of hypoxic or normoxic recovery by means of a simulated 15 min all-out time trial. During the 7h post-exercise window, biological samples are collected (muscle biopsies, venous blood samples, urine, capillary blood samples). Moreover, blood and muscle oxygenation, peripheral blood flow and cognitive function are assessed at regular timepoints.

Inclusion Criteria:

1. Written informed consent must be obtained prior to any experimental procedures
2. Biological male or biological females using oral contraception between 18 and 35 years old
3. Recreational or competitive cyclists performing regularly cycling training sessions with an average training volume of more than 6 hours per week
4. Good health status confirmed by a medical screening
5. Body Mass Index (BMI) between 18 and 25 kg/m2

Exclusion Criteria:

1. Any kind of injury/pathology that is a contra-indication for hypoxic exposure and/or to perform high-intensity exercise, evaluated by a sport medical screening
2. Intake of any medication or nutritional supplement that is known to affect exercise or performance. Intake will be assessed during recruitment and the sport medical screening.
3. Intake of analgesics, anti-inflammatory agents, or supplementary anti-oxidants, within two weeks of study participation.
4. Recent residence or training under hypoxia; more than 7 days exposure to altitude > 1500 m during the 3 months preceding the study.
5. Blood donation within 3 months of study participation.
6. Habitual smoking
7. Pre-existing, diagnosed psychiatric conditions or anxiety
8. Females that are pregnant or are planning to be pregnant before the end of the study (end of May 2024)
9. Depression or anxiety as assessed by the Beck Depression Inventory 25 (Appendix 2) and Beck Anxiety Inventory 26 (Appendix 3). Only a score in the range of 'normal ups and downs' (score 1-10) for depression or 'minimal anxiety' (score 0-7) for anxiety are tolerated.
10. History of addiction or excessive caffeine/alcohol consumption assessed by a questionnaire (Appendix 4).
11. Any other reason that might pose undue risk to the participant, or introduce bias into the study outcomes, at the discretion of the research team.