About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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
Disqualifiers
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
Trial design
Crossover
Treatments tested in this trial
Caffeine (Constant Daily Dose)
Dietary supplementOral caffeine capsule at 3 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).
Placebo (Constant Daily Dose)
Dietary supplementIdentical-appearing placebo capsule consumed at the same times as the caffeine intervention.
Caffeine (Escalating Dose)
Dietary supplementOral caffeine starting at 3 mg/kg/day and increasing incrementally to reach 6 mg/kg/day by week 4.
Placebo (Escalating Dose)
Dietary supplementPlacebo capsule daily for 4 weeks with simulated dose escalation protocol, then crossover to escalating caffeine after 2-week washout.
Caffeine (Training Days Only)
Dietary supplementOral caffeine capsule at 3 mg/kg body weight, consumed only on training days approximately 60 minutes before exercise.
Placebo (Training Days Only)
Dietary supplementPlacebo capsule only on training days for 4 weeks, then crossover to caffeine after 2-week washout.
Treatment groups
6
Treatment groupsSee each treatment group below.
Trial outcomes
Primary outcomes
Change in Plasma Proteomic Fractional Synthesis Rate (FSR)
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
Change in total lean body mass measured using dual-energy X-ray absorptiometry (DXA), reported in kilograms.
Change in Muscle Volume Measured by DXA
Change in muscle volume calculated based on regional muscle measurements obtained using DXA.
Change in Maximal Strength Assessed by 1RM/3RM Tests
Change in maximal strength assessed using one-repetition maximum (1RM) or three-repetition maximum (3RM) tests performed in the bench press and squat exercises.
Secondary outcomes
Change in Serum Hormonal Concentrations
Change in serum concentrations of insulin, cortisol, testosterone, and insulin-like growth factor 1 (IGF-1), assessed using standard biochemical analyses.
Self-Reported Sleep Quality Score
Self-reported sleep quality total score assessed using validated sleep questionnaires. Higher scores will indicate better sleep quality.
Subjective Recovery Score Assessed by Likert Scale
Subjective recovery score assessed using a Likert-type scale following each supervised training session. Higher scores will indicate better perceived recovery.
Adverse Events
Number and severity of reported adverse events, including palpitations, anxiety, restlessness, insomnia, headache, and gastrointestinal discomfort.
Sponsors and contacts
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Istanbul University - Cerrahpasa
Lead sponsor
İstanbul Yeni Yüzyıl Üniversitesi
Collaborator
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