Adaptation, Exercise Performance, Muscle Hypotrophy, Muscle Strength
Conditions
Keywords
Caffeine, Resistance Training, Muscle Adaptation, Supplementation, Strength Training, Hypertrophy
Brief summary
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.
Detailed description
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.
Interventions
DIETARY_SUPPLEMENTCaffeine (Constant Daily Dose)
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).
DIETARY_SUPPLEMENTCaffeine (Escalating Dose)
• Oral caffeine starting at 2 mg/kg/day and increasing incrementally to reach 6 mg/kg/day by week 10.
DIETARY_SUPPLEMENTCaffeine (Training Days Only)
Oral caffeine capsule at 4 mg/kg body weight, consumed only on training days approximately 60 minutes before exercise.
DIETARY_SUPPLEMENTplacebo capsule
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).
Sponsors
Istanbul University - Cerrahpasa
İstanbul Yeni Yüzyıl Üniversitesi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Caffeine and placebo supplements are identical in appearance, taste, and packaging. Supplements are pre-packaged and coded by an independent pharmacist not involved in the study. Neither participants, investigators conducting training sessions and assessments, nor outcome assessors analyzing DXA scans, performance tests, and blood samples will know group assignments. Unblinding will occur only after database lock and completion of statistical analysis.
Intervention model description
This is a parallel-group, randomized, double-blind, placebo-controlled trial with four parallel supplementation strategies: (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. All participants undergo supervised resistance training three times per week.
Eligibility
Sex/Gender
MALE
Age
18 Years to 30 Years
Healthy volunteers
Yes
Inclusion criteria
* Male sex and age between 18 and 30 years * Daily caffeine intake \<100 mg/day * resistance-training experience ≥1 year and \<3 years * Body mass index (BMI) between 18.5-25 kg/m2 * Willingness to attend all training and testing sessions regularly * Provision of written informed consent after being fully informed about the study
Exclusion criteria
* Presence of cardiovascular, metabolic, renal, hepatic, or other serious chronic diseases * Diagnosed psychiatric disorders or severe caffeine intolerance/allergy * Use of medications affecting caffeine metabolism or muscle anabolism (e.g., beta-blockers, antidepressants, anabolic steroids) * Musculoskeletal injuries that prevent safe resistance training * Smoking or alcohol consumption at levels that could affect study outcomes * Concurrent participation in another exercise intervention study * Inability to tolerate DXA scanning or blood sampling
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Lean Body Mass Measured by DXA | Baseline and post-test (after completing 10 weeks of interventions) | Change in total lean body mass measured using dual-energy X-ray absorptiometry (DXA), reported in kilograms. |
| Change in Fat Mass Measured by DXA | Baseline and post-test (after completing 10 weeks of interventions) | Change in fat mass measured using DXA. |
| Maximal Strength | Baseline, and post-test (after completing 10 weeks of interventions) | 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. |
| Total Training Volume Load | During the intervention period (all training sessions). | Total training volume load calculated as the sum of lifted load using the formula (kilograms × repetitions × sets) accumulated during each intervention period. |
| Change in Skeletal Muscle Thickness | Baseline and post-test (after completing 10 weeks of interventions) | Change in skeletal muscle thickness measured using B-mode ultrasound, reported in mm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Muscular endurance | Baseline, and post-test (after completing 10 weeks of interventions) | 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. |
| Neuromuscular function | Baseline and post-test (after completing 10 weeks of interventions) | It will be measured by the countermovement jump (CMJ) test on a force platform. |
| Resting concentrations of testosterone | Baseline, and post-test (after completing 10 weeks of interventions) | They will be measured using standard biochemical analyses. |
| Plasma epinephrine responses to exercise | 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. | They will be measured using standard biochemical analyses. |
| Recovery | Before each of the 30 training sessions during the study. | 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). |
| Adverse Events | From initiation of the 4-week caffeine abstinence period through completion of the post-intervention assessments, monitored throughout the study (approximately 16 weeks). | Adverse events will be assessed using a standardized questionnaire administered throughout the study. |
| Sleep quality | Baseline and post-test (after completing 10 weeks of interventions). | It will be assessed by the Pittsburgh Sleep Quality Index (PSQI). |
| Rate of perceived exertion | After each supervised training session, participants were assessed throughout the 10-week intervention period (30 training sessions). | 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. |
| Resting concentrations of insulin-like growth factor-1 (IGF-1) | Baseline, and post-test (after completing 10 weeks of interventions) | They will be measured using standard biochemical analyses. |
| Resting concentrations of cortisol | Baseline, and post-test (after completing 10 weeks of interventions) | They will be measured using standard biochemical analyses. |
| Resting concentrations of creatine kinase | Baseline, and post-test (after completing 10 weeks of interventions) | They will be measured using standard biochemical analyses. |
| Serum cortisol responses to exercise | 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. | They will be measured using standard biochemical analyses. |
| Plasma norepinephrine responses to exercise | 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. | They will be measured using standard biochemical analyses. |
Countries
Turkey (Türkiye)
Outcome results
None listed