Study of Different Caffeine Supplementation Strategies on Resistance Training-Induced Adaptations
Overview
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Sponsor
- Istanbul University - Cerrahpasa
- Enrollment
- 180
- Locations
- 1
- Primary Endpoint
- Change in Plasma Proteomic Fractional Synthesis Rate (FSR)
Overview
Brief Summary
This randomized, double-blind, placebo-controlled crossover trial investigates the effects of three different caffeine supplementation strategies on resistance training-induced adaptations in 180 caffeine-naive, inactive young adult males. Participants will undergo two 4-week supervised resistance training programs separated by a 2-week washout/crossover period. The three caffeine strategies are: (1) constant daily low-moderate dosing (3 mg/kg/day), (2) gradually escalating dose (3 to 6 mg/kg across weeks), and (3) training-day-only caffeine (3 mg/kg/day). Primary outcomes include non-invasive measures of integrated anabolism and hypertrophy (D2O-derived plasma proteomic fractional synthesis rate, DXA muscle volume) and strength metrics. Secondary outcomes include hormonal responses (insulin, cortisol, testosterone, IGF-1), 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 3-6 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: 180 caffeine-naive, physically inactive young adult males aged 18-30 years will be randomly assigned to one of three caffeine supplementation strategies (n=60 per strategy). Within each strategy, 30 participants will receive caffeine and 30 will receive placebo for 4 weeks. Following a 2-week washout/crossover, interventions will be switched. All participants will undergo supervised resistance training 3 times per week. OUTCOMES: Primary endpoints include deuterium oxide (D2O)-derived plasma proteomic fractional synthesis rate (FSR), DXA-measured lean tissue mass and muscle volume, maximal strength (1RM or 3RM for bench press and squat), and training volume metrics. Secondary outcomes include hormonal and metabolic time-courses, sleep quality, subjective recovery scores, and adverse event monitoring. STATISTICAL ANALYSIS: Linear Mixed Models will be used to analyze the data.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- Triple (Participant, 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, strength tests, and blood samples will know group assignments. Unblinding will occur only after database lock and completion of statistical analysis.
Eligibility Criteria
- Ages
- 18 Years to 30 Years (Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Male sex and age between 18-30 years
- •No history of caffeine use or very low habitual intake (\<50 mg/day)
- •No participation in a regular resistance training program in the past 6 months
- •Body mass index (BMI) between 18.5-30 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, blood sampling, or D2O ingestion procedures
Arms & Interventions
Strategy 3: Training Days Only - Caffeine First
Participants receive caffeine at 3 mg/kg only on training days (3 times per week) for the first 4-week intervention period, followed by a 2-week washout, then cross over to placebo for the second 4-week period. Supervised resistance training is performed 3 times per week throughout both periods.
Intervention: Caffeine (Training Days Only) (Dietary Supplement)
Strategy 1: Constant Daily Dose - Caffeine First
Participants receive caffeine at a constant daily dose of 3 mg/kg/day for the first 4-week intervention period, followed by a 2-week washout, then cross over to placebo for the second 4-week period. Supervised resistance training is performed 3 times per week throughout both periods.
Intervention: Caffeine (Constant Daily Dose) (Dietary Supplement)
Strategy 1: Constant Daily Dose - Placebo First
Participants receive placebo for the first 4-week intervention period, followed by a 2-week washout, then cross over to caffeine at a constant daily dose of 3 mg/kg/day for the second 4-week period. Supervised resistance training is performed 3 times per week throughout both periods.
Intervention: Placebo (Constant Daily Dose) (Dietary Supplement)
Strategy 2: Escalating Dose - Caffeine First
Participants receive caffeine with a gradually escalating dose starting at 3 mg/kg/day in week 1 and increasing to 6 mg/kg/day by week 4, followed by a 2-week washout, then cross over to placebo for the second 4-week period. Supervised resistance training is performed 3 times per week throughout both periods.
Intervention: Caffeine (Escalating Dose) (Dietary Supplement)
Strategy 2: Escalating Dose - Placebo First
Participants receive placebo for the first 4-week intervention period, followed by a 2-week washout, then cross over to caffeine with a gradually escalating dose (3 to 6 mg/kg/day) for the second 4-week period. Supervised resistance training is performed 3 times per week throughout both periods.
Intervention: Placebo (Escalating Dose) (Dietary Supplement)
Strategy 3: Training Days Only - Placebo First
Participants receive placebo only on training days (3 times per week) for the first 4-week intervention period, followed by a 2-week washout, then cross over to caffeine at 3 mg/kg for the second 4-week period. Supervised resistance training is performed 3 times per week throughout both periods.
Intervention: Placebo (Training Days Only) (Dietary Supplement)
Outcomes
Primary Outcomes
Change in Plasma Proteomic Fractional Synthesis Rate (FSR)
Time Frame: Baseline; End of Intervention Period 1 (Week 4); End of Intervention Period 2 (Week 4)
Change in plasma proteomic fractional synthesis rate (FSR) calculated using the deuterium oxide (D2O) method. This physiological parameter will be reported as an indicator of integrated muscle protein synthesis.
Change in Lean Body Mass Measured by DXA
Time Frame: Baseline; End of Intervention Period 1 (Week 4); End of Intervention Period 2 (Week 4)
Change in total lean body mass measured using dual-energy X-ray absorptiometry (DXA), reported in kilograms.
Change in Muscle Volume Measured by DXA
Time Frame: Baseline; End of Intervention Period 1 (Week 4); End of Intervention Period 2 (Week 4)
Change in muscle volume calculated based on regional muscle measurements obtained using DXA.
Change in Maximal Strength Assessed by 1RM/3RM Tests
Time Frame: Baseline; End of Intervention Period 1 (Week 4); End of Intervention Period 2 (Week 4)
Change in maximal strength assessed using one-repetition maximum (1RM) or three-repetition maximum (3RM) tests performed in the bench press and squat exercises.
Total Training Volume Load
Time Frame: Intervention Period 1 (Weeks 1-4); Intervention Period 2 (Weeks 1-4)
Total training volume load calculated as the sum of lifted load using the formula (kilograms × repetitions × sets) accumulated during each intervention period.
Secondary Outcomes
- Change in Serum Hormonal Concentrations(Baseline; Week 2; End of Intervention Period 1 (Week 4); Baseline; Week 2; End of Intervention Period 2 (Week 4))
- Self-Reported Sleep Quality Score(Weekly during Intervention Period 1 (Weeks 1-4); Weekly during Intervention Period 2 (Weeks 1-4))
- Subjective Recovery Score Assessed by Likert Scale(After each supervised training session during Intervention Period 1; After each supervised training session during Intervention Period 2)
- Adverse Events(Throughout the entire study duration (8 weeks))
Investigators
Abdullah Demirli
Assistant Professor
Istanbul University - Cerrahpasa