Why do People Respond Differently to Resistance Training?

Study Overview
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Brief Summary
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It is well known that regular resistance training (RT) can have health benefits. However, considerable heterogeneity in RT responses has been observed. The mechanisms underlying an individual's ability to respond to RT are mainly unknown but involve a complex network of genomic and non-genomic factors. The investigators aim to examine heterogeneity in physiological responses to RT while closely monitoring other environmental factors (e.g., physical activity levels, nutrition, sleep, and stress). Participants are healthy sedentary men and women aged 18-45 (n=240). A controlled 12-week RT intervention will be conducted to characterize RT response. Data will be collected before, during, and after the study period by using measurements of body composition, muscle size, and physical fitness characteristics, as well as by collecting blood samples and questionnaires. The investigators will identify the underlying factors contributing to why people differ in their physiological responses to RT. For this, comprehensive background data will be collected to identify common denominators underlying individual differences in response to RT. The investigators will use sophisticated analytical methods to reveal new predictors of training response for different traits. This research project aims to gain insight into the sources of individual variation in physiological responses to RT. On this basis, exercise training can be personalized to optimize the benefits of RT for all individuals. Ultimately, the investigators will also be able to justify better using RT as part of individualized healthcare strategies in the future.

Detailed Description
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The benefits of regular resistance training (RT) are well known, but it is also well known that tremendous inter-individual variability can be detected in responses to RT. The reason(s) for individual variations in responses to RT is a very complex physiological phenomenon and is still poorly known. The individual variation in trainability suggests genetic diversity but non-genetic determinants potentially contribute significantly to training responses. The investigators hypothesize that in this study, a broad spectrum of adaptive responses to RT is detected. By scrutinizing participants' backgrounds, it can be elucidated why individuals respond differently to regular RT. Furthermore, it is hypothesized that the investigators can identify specific predictive markers for RT responsiveness. That is possible by combining information on training responsiveness with the personal characteristics of the participant. Healthy young adults will be recruited to the study to understand the biological basis of heterogeneity in exercise responses by minimizing potential age and health-related physiological confounders. They are premised to respond positively to the study's primary outcome, which is maximal lower limb muscle strength. To collect comprehensive data, the number of participants is maximized within practical limitations, and thus, 240 participants are recruited. According to the investigators' extensive experience in fully supervised exercise training interventions with comprehensive and time-consuming physiological measures, this is the maximum number of participants that can examine within the timeframe allocated for data collection. Participants comprise an equal proportion of men and women, and sex differences in RT responsiveness will be investigated as a secondary aim of the study. The study design is a single-arm trial. After assessing eligibility, participants engage in the baseline measurements and the 12-week fully supervised RT intervention. The training protocol is identical for each participant. The participants will train two times weekly, and the program will target all major muscle groups. Each training session includes exercises for the lower (leg presses, knee extensions/flexions) and upper body (bench presses, biceps curls, and seated row). For the first two weeks, the participants will perform  15 repetitions per set (approximately 50-70% of the one repetition maximum, 1RM) and three sets per exercise. After that, the training load will be at an 8- to 12-RM zone for four sets per exercise. The change in muscle strength (10RM test) is assessed in the gym at 2-week intervals. Loads are increased progressively for the next 2-week period if the prescribed number of repetitions is completed for a given load. A questionnaire on perceived exertion in each exercise session (sRPE) will be obtained to evaluate the participant's intrinsic effort in performing exercises. The training is executed in a local university gym with a standardized time of day, and training diaries are used to track the training loads. The measurements are obtained at baseline and after the intervention. Participants are informed of the study goals and are carefully familiarized with study protocols. All the tests are carried out at the same time of day. The participants are given feedback on their test results during the project. The primary outcome of this study is maximum leg press strength. Gains in muscle strength are determined by increased muscle size and/or improvements in capability to activate working muscles. In addition to genetics, environmental factors are essential in explaining individuality in training responses. In this project, the investigators focus on gathering comprehensive data on variables of participants' background, nutrition, health status, and physical activity that can potentially influence the heterogeneity of RT adaptations.

Official Title
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Precision Exercise (PreEx): Identifying the Determinants of Inter-individual Variation in Resistance Training Responses

Conditions
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Resistance Training

Intervention / Treatment
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* Other: Resistance training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 18-45 healthy (e.g., no diagnosed type 2 diabetes, cardiovascular disease, musculoskeletal disorders, etc.) limited experience in resistance training 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Training group<br>Resistance training | Other: Resistance training<br>* 12-week resistance training intervention<br>* Other names: Exercise training;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in lower limb maximal strength after 12-week resistance training intervention | Maximal voluntary concentric muscle strength of leg extensors (kg) is determined in horizontal leg press device (David 210) via one-repetition maximum (1RM) test according to the NCSA guidelines | 12-weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in m.Vastus Lateralis cross-sectional area (CSA) after 12-week resistance training intervention | Vastus Lateralis muscle CSA (cm^2) is determined at mid-thigh using a B-mode axial plane ultrasound (model SSD-α10, Aloka, Tokyo, Japan) with a 10 MHz linear-array probe (60 mm width) in extended-ﬁeld-of-view mode (23 Hz sampling frequency) | 12-weeks | 
| Change in whole body fat-free mass after 12-week resistance training intervention | Fat-free body mass (kg) is measured at morning after overnight fasting by bioimpedance device (InBody 770, Biospace Co. Seoul, Korea) | 12-weeks | 
| Change in whole body fat mass after 12-week resistance training intervention | Fat body mass (kg) is measured at morning after overnight fasting by bioimpedance device (InBody 770, Biospace Co. Seoul, Korea) | 12-weeks | 
| Change in waist circumference after 12-week resistance training intervention | Waist circumference is measured by measuring tape horizontally around the waist above hipbones after exhaling in standing position | 12-weeks | 
| Change in grip strength after 12-week resistance training intervention | The maximal isometric grip strength is measured on dominant side at 90 degree elbow angle in a sitting position using a dynamometer chair (Good Strength, Metitur, Palokka, Finland) | 12-weeks | 
| Change in maximal vertical jump height after 12-week resistance training intervention | The countermovement jump height is calculated by measurement of flight time by jump mat | 12-weeks | 
| Change in blood count determined from the venous blood sample obtained at morning after overnight fasting before and after 12-week resistance training intervention | Full blood count is measured by hematology analyzer (Sysmex KX-21N, Sysmex Corp., Japan) | 12-weeks | 
| Change in C-reactive protein (CRP) determined from the venous blood sample obtained at morning after overnight fasting before and after 12-week resistance training intervention | Serum CRP is measured by high-sensitivity ELISA kit (Quantikine HS, R&D Systems, Minneapolis, USA). | 12-weeks | 
| Change in metabolomics determined from the venous blood sample obtained at morning after overnight fasting before and after 12-week resistance training intervention | A high-throughput serum Nuclear Magnetic Resonance (NMR) metabolomics platform will be used for the absolute quantification of serum lipids and metabolite profile. | 12-weeks | 
| Self-reported measure of physical activity | Investigated by the Global Physical Activity Questionnaire (GPAQ), a standardized 16-question questionnaire that assesses categories of low, moderate, and vigorous physical activity (in MET minutes per week) in three different domains: activity at work, travel to and from places, and leisure activities. Also, sedentary behavior (minutes per week) is assessed. | Baseline and after 12-week resistance training intervention | 
| Sleep self-assessment | Investigated by The Pittsburgh Sleep Quality Index (PSQI) questionnaire which consists of questions of a four-point Likert scale (0-3), with higher scores representing greater sleep difficulties. | Baseline and after 12-week resistance training intervention | 
| Self-report of eating disorder behaviors and attitudes | Investigated by the Eating Disorder Examination Questionnaire (EDE-Q), which assesses the extent, frequency, and severity of eating disorder-related behaviors on a seven-point Likert scale or occurrence over a 28-day period. Higher scores represent higher levels of eating disorders. | Baseline and after 12-week resistance training intervention | 
| Self-estimated dietary intake | Investigated by a food frequency questionnaire (FFQ) which consists of a finite list of foods and beverages with response categories to indicate usual frequency of consumption over the time period queried. | Baseline and after 12-week resistance training intervention | 
| Self-estimated energy availability | Investigated by the Low Energy Availability Questionnaire (LEAF-Q for females, LEAM-Q for men) which identifies persons at risk for low energy availability by utilizing subsets of gastrointestinal symptoms, injury frequency, and menstrual dysfunction (in women). A score ≥8 indicates that an individual is at risk for low energy availability. | Baseline and after 12-week resistance training intervention | 
| Self-measure of perceived stress | Investigated by Perceived Stress Scale (14 items); from 0 (never) to 4 (very often) | Baseline and after 12-week resistance training intervention | 
| Self-assessed personality traits | Investigated by Finnish NEO Five-Factor Inventory | Baseline |