Clinical trial NCT05764018: Caffeine and Hypoxia During Exercise in Males and Females
Official title: Sex Differences in the Acute Effects of Caffeine Supplementation on Exercise in Normobaric Hypoxia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Caffeine
Hypoxia
Keywords: Caffeine
Hypoxia
Female physiology
Exercise
Lead sponsor: Jozef Stefan Institute
Sponsor class: OTHER
First posted: 2023-03-10
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Participants will perform four trials, to cover both levels of two factors; normoxia vs. hypoxia, and placebo vs. caffeine
Primary purpose: OTHER

Brief summary: Several high-altitude destinations recommend their visitors to avoid caffeine, theoretically due to the associated diuresis which could contribute to acute mountain sickness. There is however no direct evidence for this association. In fact, caffeine ingestion is known to improve exercise performance at sea level, and may therefore help mountaineers during expeditions.

Sport science research is largely conducted in male participants, and the findings from these studies are assumed to apply to the female population. Given the known sex differences in body composition, hormones, and other physiological factors, this may not be appropriate. It is therefore important to conduct research in women, to allow for female-specific recommendations.

Detailed description: As a result of transportation modernisation and tourism development, an increasing number of individuals are visiting high-altitude destinations for work and leisure purposes. The resulting exposure to (hypobaric) hypoxia is known to reduce exercise capacity due to a reduction in maximal oxygen uptake induced by lower oxygen pressure throughout the oxygen cascade. Several high-altitude destinations recommend their visitors to reduce or completely avoid caffeine intake during their stay. This recommendation is often based on the diuretic effects of caffeine, as the increased fluid loss through urine could accentuate dehydration, potentially contributing to feelings of acute mountain sickness. However, there is currently no scientific evidence to substantiate this recommendation. In fact, caffeine is known to be a particularly effective stimulant to improve exercise performance at sea level. Caffeine could therefore help mountaineers who engage in relatively intense physical activity during expeditions at altitude. The mechanisms underlying the ergogenic effects of caffeine are believed to originate centrally and peripherally. Of particular interest is the potential for caffeine to increase ventilation at submaximal and maximal exercise intensities. In a high-altitude environment, this could help to offset exercise- and hypoxia-induced hypoxemia, thereby enhancing exercise capacity.

Some studies have indeed provided evidence for the notion that caffeine could enhance exercise capabilities in hypoxia. Caffeine doses of 4.0 - 6.0 mg/kg body mass have been assessed, in (simulated and terrestrial) altitude environments equating to 2000 - 4300 m. In each case, it appeared that exercise performance and/or capacity at altitude could indeed be enhanced by caffeine ingestion. However, further mechanistic work is required, particularly in the assessment of the physiological effects of caffeine beyond typical exercise performance (time trial) and exercise capacity (peak power output, maximal oxygen uptake) outcomes. An enhanced holistic understanding of respiratory, cardiovascular, muscular and metabolic responses to exercise, caffeine and hypoxia is necessary to understand if caffeine ingestion at altitude is advisable.

Sport science research is largely conducted in male participants, and the findings from these studies are assumed to also apply to the female population. However, given the known sex differences in body composition, hormones, and other physiological factors, these assumptions may not be appropriate. It is therefore important to conduct research in women, to allow female-specific recommendations to be applied to athletes and to the general population.

As these are important considerations, the aim of this project is to investigate the effects of caffeine supplementation on exercise in hypoxia, and to determine whether these effects are influenced by sex differences.

24 healthy adult participants (12 male, 12 female) will be recruited to take part in the project. A preliminary testing session will be used to determine the maximal oxygen uptake of the participants in normoxia, and to familiarise them with the main trial protocol. A second preliminary laboratory visit will be used to measure the resting metabolic rate of the participants.

The main phase of the experiment will be a four-trial randomised crossover study; normoxia (ambient) vs. hypoxia (fraction of inspired oxygen = 0.13) and placebo (20 g maltodextrin) vs. caffeine (20 g maltodextrin + 6 mg/kg body mass caffeine). Participants will avoid caffeine, alcohol and intense exercise for 24 h prior to each laboratory visit. They will also replicate their diet for 24 h before each main trial. Each main trial will involve a 20-minute moderate-intensity cycling period, immediately followed by an incremental exercise test to exhaustion. Participants will be blinded to the environmental condition and the contents of the test drink. Outcome measures will include gas exchange variables, blood glucose/lactate concentration, muscle and brain oxygenation, blood oxygen saturation, heart rate and rating of perceived exertion. These measurements will provide a holistic overview of the broad physiological response to exercise, hypoxia and caffeine.

Eligibility criteria: Inclusion Criteria:

* Regularly physically active (at least 30 mins of structured exercise 5 times per week).
* Sea-level natives.

Exclusion Criteria:

* presence of any medical risk factors to exercise and/or exposure to altitude
* presence of any medical condition that would make the protocol unreasonably hazardous for the participant
* smokers
* exposure to altitude above 2000 m in the last 2 months

Primary outcomes:
measure: Peak oxygen uptake
timeFrame: Immediately prior to volitional exhaustion during the incremental exercise test
measure: Maximal aerobic power
timeFrame: At the instant of volitional exhaustion during the incremental exercise test
measure: Peak minute ventilation
timeFrame: Immediately prior to volitional exhaustion during the incremental exercise test
measure: Peak heart rate
timeFrame: Immediately prior to volitional exhaustion during the incremental exercise test
measure: Muscle oxygenation nadir
timeFrame: Immediately prior to volitional exhaustion during the incremental exercise test
measure: Peak blood lactate concentration
timeFrame: Immediately after volitional exhaustion during the incremental exercise test
Secondary outcomes:
measure: Submaximal oxygen uptake
timeFrame: From the onset of exercise to the end of the submaximal exercise period at 20 minutes.
measure: Submaximal minute ventilation
timeFrame: From the onset of exercise to the end of the submaximal exercise period at 20 minutes.
measure: Submaximal substrate oxidation
timeFrame: From the onset of exercise to the end of the submaximal exercise period at 20 minutes.
measure: Submaximal muscle oxygenation
timeFrame: From the onset of exercise to the end of the submaximal exercise period at 20 minutes.
measure: Submaximal brain oxygenation
timeFrame: From the onset of exercise to the end of the submaximal exercise period at 20 minutes.
measure: Submaximal heart rate
timeFrame: From the onset of exercise to the end of the submaximal exercise period at 20 minutes.
measure: Blood glucose concentration
timeFrame: At rest prior to exercise, and at the end of the submaximal exercise period at 20 minutes.
measure: Blood lactate concentration
timeFrame: At rest prior to exercise, and at the end of the submaximal exercise period at 20 minutes.
measure: Rating of perceived exertion
timeFrame: Every 5 minutes throughout the 20 minute submaximal exercise period.
Other outcomes:
Locations:
city: Ljubljana
country: Slovenia
facility: University of Ljubljana
Study officials:
affiliation: University of Ljubljana
name: Tadej Debevec, PhD
role: PRINCIPAL_INVESTIGATOR
References: