Resistance Training, Detraining, and Retraining Study 2024 (TraDeRe2024)

The goals of our research project are to identify factors explaining inter-individual variation in responses to resistance training (RT) and the baseline determinants underlying an individual's sensitivity to respond to RT. Moreover, investigators aim to assess whether a responsiveness to RT predicts responsiveness to endurance training (ET). Thus, investigators aim to gain a deeper understanding of exercise adaptation processes. The main questions investigators aim to answer are:

* Can the physiological responses of one RT intervention be extrapolated to a subsequent RT intervention?
* If so, what are the mechanisms underlying differing skeletal muscle growth responses in low, and high responders of skeletal muscle hypertrophy?
* If so, do the low responders of skeletal muscle growth respond more favourably when the amount of RT is increased?
* Are the high, moderate, and low responders of RT also the highest, moderate, and lowest responders to ET?

To examine these main research questions, high (n=30), low (n=30), and moderate (n=30) responders of skeletal muscle growth in response to RT (intervention I, NCT05874986) are reallocated into a subsequent 12-week RT intervention (intervention II) after a detraining period. A subgroup of these participants (n=10) will engage in a 6-week control period before starting the second RT period. Additionally, after intervention II, participants will participate in an ET intervention, lasting 6 weeks.

In this intervention II, reallocated participants will be:

* Resistance training with supervision for 12 weeks
* Consuming deuterium oxide for the assessment of muscle protein synthesis
* Consuming D3-3-methylhistidine for the assessment of acute muscle protein breakdown
* Consuming D3-creatine for the examination of whole-body skeletal muscle mass
* Providing a spot urine sample six (6) times, and urine collection for 24 hours performed twice
* Providing saliva samples (30-32 in total) for the assessment of body water enrichment of deuterium
* Providing a muscle biopsy four or five (4-5) times during the study
* Providing a blood sample fourteen (14) times during the study
* Assessed for body composition and body volume four or five times (4-5) during the study
* Participating in muscle size, maximal dynamic strength and TMS measurements four or five (4-5) times during the study
* Asked to answer questionnaires related to e.g. stress, physical activity, sleep, perceived exertion, and diet
* Participating in recovery measurements before and after the second-to-last and the last RT bout, and once in the days between these RT bouts, consisting of six (6) body volume measurements and six (6) maximal voluntary isometric contraction (kg) tests using horizontal leg press for the assessment of neuromuscular recovery
* Participating in an acute resistance exercise (RE) after the 12-week RT intervention.

Furthermore, in the ET intervention, participants will be:

* Participating in a familiarization session and resting electrocardiograph measurements before the intervention
* Participating in endurance testing consisting of body composition, movement economy, and incremental RAMP testing before and after ET intervention
* Endurance training with supervision for 6 weeks, three times a week.

While the diverse health and performance benefits of resistance training (RT) are widely recognized, some individuals demonstrate notably divergent responses to RT intervention. This phenomenon is termed inter-individual response variation to RT. However, despite the prevalence of these research findings, the precise underlying mechanisms contributing to these differential RT responses remain ambiguous. Finally, it is currently unknown whether a responsiveness to RT predicts responsiveness to ET within the same set of participants, as this area of research is critically understudied.

Investigators aim to investigate the cellular, molecular, and neuromuscular mechanisms behind the plausible RT response variability intra- and inter-individually, using trial-to-trial, i.e. resistance training, detraining, and retraining design. Moreover, as the impact of diverse polygenic effects on RT responsiveness is yet to be determined, investigators will employ a multi-OMIC (genomic, epigenomic, transcriptomic, proteomic, and metabolomic) approach to unravel previously unknown denominators of RT responsiveness. Finally, numerous environmental factors, e.g. nutrition, stress, sleep, and physical activity are monitored during the study to assess the effects of non-physiological mechanisms on RT response variability.

In our study, 362 healthy male and female participants in total started in the study and were destined to undergo an RT period of 12 weeks in two separate periods (intervention I refers to NCT05874986). Then, a subset of the participants from intervention I will be reallocated into intervention II based on the magnitude increase of m. vastus lateralis (VL) cross-sectional area (CSA) assessed by ultrasound using extended-field-of-view mode. Similar to intervention I, intervention II will be performed in separate periods similarly to the data collection I and II of intervention I to first accumulate approximately 32 weeks of detraining for both cohorts, after which 12 weeks of RT is performed.

Moreover, a subset (n=30) of the participants aged 40-50 from intervention I not selected for intervention II have a chance to take part in a 10-week home training sub-study. These participants will be randomized to a non-training control group (n=15) and a home training group (n=15). The home training group will carry out a 10-week RT period utilizing muscle-strengthening activities in their home. This sub-study investigates how minimally supervised RT executed at home after supervised gym RT can maintain muscle strength and size compared to non-training. Home training is flexible, time-saving, and inexpensive. It is also done twice weekly using safe and effective training protocols and movements. Home-based training includes pistol squat, reverse nordic, push up, and bent-over row, and bicep curl exercises. To achieve progression, the total load will be increased by increasing the number of repetitions per set, and/or increasing the load by using a progression from easier to more difficult techniques and/or by adding resistance bands, which will be provided to participant's free of charge for the duration of the study. Participants will be contacted regularly to ensure motivation and adherence to home exercise. All the participants in this sub-study, as well as the other participants not selected for intervention II are offered a self-directed, non-supervised 7-week RT period with a similar design as in intervention I with access to our gym located in our Faculty's building. VL CSA, horizontal leg press 1 repetition maximum, and body composition will be assessed before and after home training and self-directed RT for each participant.

In intervention II, participants will be performing RT similarly to intervention I. However, for the last 5 weeks of the intervention, RT volume will be increased by 40 % for the lower body exercises to assess the impact of RT volume increment on RT responses. After 12 weeks of RT, an experimental RT session will be conducted to assess the acute physiological responses to resistance exercise. The experimental session will consist of five heavy sets of both horizontal leg press and leg extension exercises. During the last RT week, participants will engage in recovery measurements before and after the second-to-last and the last RT bout, and once during the days between these two bouts. After 12 weeks of RT, participants will be performing an additional acute resistance exercise session. All the participants NOT selected for intervention II are able to participate in a self-directed, 6-week RT period with measurements before and after this period. These measurements include body composition, muscle size (VL CSA and muscle thickness of elbow flexors) and muscle strength (dynamic 1RM of horizontal leg press and barbell scott curl) assessments. A subgroup of the participants (n=10) will engage in a control period of 6 weeks in duration, before the onset of RT.

After the intervention II, participants will begin a washout period lasting approximately 16 weeks (± 2), during which participants are advised to abstain from RT and ET. After a washout period, participants will participate in the familiarization measurements regarding the ET intervention. In familiarization, participants are measured with an electrocardiogram (ECG), after which a medical doctor will evaluate the resting ECG results to verify the eligibility of each participant. Moreover, participants will be habituated to movement economy testing by performing 3x3 min low-intervals with loads of 30-55-80 watts for females and 50-80-110 watts for males, respectively, and other included measurements. After familiarization and eligibility assessment, baseline measurements will be conducted the following week. Baseline measurements include body composition and volume assessment with a 3D optical body scanner, a 4 x 4 minute movement economy test with individualized, progressive loads determined in the familiarization (last load near the aerobic threshold). Movement economy intervals are performed with no rest in between. Finally, a maximal oxygen uptake (VO2max) will be measured breath-by-breath with an incremental RAMP test. The starting intensity will be 30 watts for both males and females, and the intensity will be increased by 30 and 25 watts per minute for males and females, respectively. The RAMP test will be performed with a self-selected cadence above 60 rounds per minute (rpm). When participants fail to maintain a cadence over 60 rpm second time, after one warning and despite heavy encouragement, the RAMP test will be terminated. All the testing will be performed using a bicycle ergometer. Heart rate, heart rate variability (HRV), expired gas analysis, arterial oxygen saturation, power output, stroke volume and cardiac output will be monitored continuously during the tests. Perceived exertion is assessed with a modified RPE scale of 0-10 after each movement economy interval and RAMP test. Blood lactate, blood glucose and hemoglobin concentrations are also measured after each movement economy interval and at the end of the RAMP test.

Endurance exercise is programmed based on the guidelines by the American College of Sports Medicine. During weeks 1-2, 45 minutes of low-intensity (= near the first ventilatory threshold) steady-state cycling is performed. In weeks 3-4, 50 minutes of cycling is performed, during which every other session includes low intensity cycling and every other session 3 x 10-minute intervals (with 4-minute rest after each interval) at moderate intensity (= between the first and the second ventilatory thresholds). Finally, in weeks 5-6, 55 minutes of cycling is performed, consisting of 4 x 10-minute intervals (with 3-minute rest after each interval) at a moderate intensity. Participants will be doing endurance exercises in groups of 2-4, and training three times a week at the standardized time of day. At the beginning of ET, appropriate training intensities are verified with blood lactate and the modified RPE scale. Training intensities at the start are decided by two blinded researchers based on the ventilatory thresholds obtained during the RAMP test. Individual training data, including heart rate, HRV, RPE, and wattage, is collected. The wattage is continuously displayed on the screen of the cycle ergometers during sessions to maintain appropriate training intensities. Wattage is increased within and between training sessions according to heart rate, lactate concentration, and modified RPE scale to establish progression. Before the onset of each interval session, a brief low-intensity steady-state warm-up of 7-8 minutes is performed.

In this study, investigators aim to identify several previously unknown molecular determinants that underlie the observed heterogeneity in RT responses. This could significantly increase the understanding of exercise physiology, which can be applied, e.g., in sports medicine, rehabilitation, and sports coaching. Moreover, this study can promote the development of personalized exercise prescriptions as part of health care. Indeed, it is vital to examine whether the same individuals respond similarly or differently to RT and ET at least in the short term. These findings can then be used to adjust individualized training programming not only as a part of health care but also regarding physical performance optimization. Finally, the findings of the study can operate as a foundational work for future research on the topic of RT response heterogeneity.

Eligibility Criteria:
Inclusion Criteria:

* age 18-50
* healthy (e.g., no diagnosed type 2 diabetes, cardiovascular disease, musculoskeletal disorders, etc.)
* prior participation in intervention I (NCT05874986)

Exclusion Criteria:

* medication affecting the cardiovascular system or metabolism
* metabolic, musculoskeletal, cardiovascular, or other diseases or disorders which may preclude the ability to perform exercise training and testing