This parallel-group, randomized, double-blind, placebo-controlled trial investigates the effects of three different caffeine supplementation strategies on resistance training-induced adaptations in 120 caffeine-naive, inactive young adult males. Participants will undergo a 10-week supervised resistance training program. The four supplementation strategies are: (1) constant daily low-moderate dosing (4 mg/kg/day), (2) gradually escalating dose (2 to 6 mg/kg across weeks), (3) training-day-only caffeine (4 mg/kg/day), and (4) placebo. Primary outcomes include maximal strength, body composition (lean body mass and fat mass), skeletal muscle thickness, and training volume progression. Secondary outcomes include muscular endurance, jump height, flight-time-to-contraction-time (FT:CT) ratio, mechanistic/biological variables (epinephrine, norepinephrine, cortisol, testosterone, creatine kinase, IGF-1), rate of perceived exertion, sleep/recovery parameters, and adverse effects.
BACKGROUND: Caffeine is a well-established acute ergogenic aid that reliably improves endurance, power, and resistance-exercise performance when consumed at typical ergogenic doses (approximately 2-6 mg/kg about 60 minutes pre-exercise). However, whether caffeine exerts direct biological effects on muscle protein balance and hypertrophy remains unclear. Regular caffeine ingestion produces partial physiological tolerance, creating the possibility that chronic supplementation elicits different outcomes than acute dosing. OBJECTIVES: This study addresses three translational questions: (1) Does constant daily low-moderate dosing potentiate training adaptations? (2) Does a gradually escalating dose strategy produce greater effects by overcoming tolerance? (3) Does training-day-only caffeine preserve acute ergogenic effects while limiting tolerance and sleep disturbance? METHODS: 120 caffeine-naive, physically inactive young adult males aged 18-30 years will be randomly assigned to one of the following groups (n=30 per group): (1) constant daily low-moderate dosing (CON, 4 mg/kg/day), (2) gradually escalating dose (ESC, 2 to 6 mg/kg across weeks), (3) training-day-only caffeine (TDO, 4 mg/kg/day), and (4) placebo (PLA). All participants will undergo supervised resistance training 3 times per week. OUTCOMES: Primary endpoints include maximal strength, body composition (lean body mass and fat mass), skeletal muscle thickness, and training volume metrics. Secondary outcomes include muscular endurance, jump height, flight-time-to-contraction-time (FT:CT) ratio, mechanistic/biological variables (epinephrine, norepinephrine, cortisol, testosterone, creatine kinase, IGF-1), rate of perceived exertion, sleep/recovery parameters, and adverse effects. STATISTICAL ANALYSIS: Linear Mixed Models will be used to analyze the data.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
120
Oral caffeine capsule at 4 mg/kg body weight, consumed daily approximately 60 minutes before training sessions (on training days) or at the same time of day (on rest days).
• Oral caffeine starting at 2 mg/kg/day and increasing incrementally to reach 6 mg/kg/day by week 10.
Oral caffeine capsule at 4 mg/kg body weight, consumed only on training days approximately 60 minutes before exercise.
Oral placebo capsule (250 mg cellulose), consumed daily approximately 60 minutes before training sessions (on training days) or at the same time of day (on rest days).
Istanbul University-Cerrahpasa, Faculty of Sport Sciences Performance Laboratory
Istanbul, Avcilar, Turkey (Türkiye)
Change in Lean Body Mass Measured by DXA
Change in total lean body mass measured using dual-energy X-ray absorptiometry (DXA), reported in kilograms.
Time frame: Baseline and post-test (after completing 10 weeks of interventions)
Change in Fat Mass Measured by DXA
Change in fat mass measured using DXA.
Time frame: Baseline and post-test (after completing 10 weeks of interventions)
Maximal Strength
Measure by one-repetition maximum (1-RM) on a lower body (Smith machine Back Squat) and two upper body (Bench Press machine and Lat Pulldown machine) exercises.
Time frame: Baseline, and post-test (after completing 10 weeks of interventions)
Total Training Volume Load
Total training volume load calculated as the sum of lifted load using the formula (kilograms × repetitions × sets) accumulated during each intervention period.
Time frame: During the intervention period (all training sessions).
Change in Skeletal Muscle Thickness
Change in skeletal muscle thickness measured using B-mode ultrasound, reported in mm.
Time frame: Baseline and post-test (after completing 10 weeks of interventions)
Muscular endurance
It will be measured by a repetitions-to-failure test on the Smith machine back squat using a load corresponding to 60% of the current 1RM.
Time frame: Baseline, and post-test (after completing 10 weeks of interventions)
Neuromuscular function
It will be measured by the countermovement jump (CMJ) test on a force platform.
Time frame: Baseline and post-test (after completing 10 weeks of interventions)
Resting concentrations of testosterone
They will be measured using standard biochemical analyses.
Time frame: Baseline, and post-test (after completing 10 weeks of interventions)
Plasma epinephrine responses to exercise
They will be measured using standard biochemical analyses.
Time frame: During the first training session of Week 1 and the final training session of Week 10, at three time points: (1) pre-supplementation, (2) immediately before exercise and (3) immediately after exercise.
Recovery
It will be assessed using the validated 0-10 Perceived Recovery Status Scale (0 to 2: very poorly recovered, 3 to 4: poorly recovered, 5 to 6: adequately recovered, 7 to 8: well recovered, and 9 to 10: fully recovered).
Time frame: Before each of the 30 training sessions during the study.
Adverse Events
Adverse events will be assessed using a standardized questionnaire administered throughout the study.
Time frame: From initiation of the 4-week caffeine abstinence period through completion of the post-intervention assessments, monitored throughout the study (approximately 16 weeks).
Sleep quality
It will be assessed by the Pittsburgh Sleep Quality Index (PSQI).
Time frame: Baseline and post-test (after completing 10 weeks of interventions).
Rate of perceived exertion
Assessed using the Borg Category-Ratio (CR10) Scale, ranging from 0 ("nothing at all") to 10 ("maximal"). Participants will report their perceived exertion after each supervised training session.
Time frame: After each supervised training session, participants were assessed throughout the 10-week intervention period (30 training sessions).
Resting concentrations of insulin-like growth factor-1 (IGF-1)
They will be measured using standard biochemical analyses.
Time frame: Baseline, and post-test (after completing 10 weeks of interventions)
Resting concentrations of cortisol
They will be measured using standard biochemical analyses.
Time frame: Baseline, and post-test (after completing 10 weeks of interventions)
Resting concentrations of creatine kinase
They will be measured using standard biochemical analyses.
Time frame: Baseline, and post-test (after completing 10 weeks of interventions)
Serum cortisol responses to exercise
They will be measured using standard biochemical analyses.
Time frame: During the first training session of Week 1 and the final training session of Week 10, at three time points: (1) pre-supplementation, (2) immediately before exercise and (3) immediately after exercise.
Plasma norepinephrine responses to exercise
They will be measured using standard biochemical analyses.
Time frame: During the first training session of Week 1 and the final training session of Week 10, at three time points: (1) pre-supplementation, (2) immediately before exercise and (3) immediately after exercise.
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