Resistance Training Adaptations and Caffeine Intake

February 7, 2026 updated by: Abdullah Demirli, Istanbul University - Cerrahpasa

Study of Different Caffeine Supplementation Strategies on Resistance Training-Induced Adaptations

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

180

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Turkey (Türkiye)
    • Avcilar
      • Istanbul, Avcilar, Turkey (Türkiye), 34010
        • Istanbul University-Cerrahpasa, Faculty of Sport Sciences Performance Laboratory
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Dietary supplement: Caffeine (Constant Daily Dose)
Oral 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 Comparator: 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.
Dietary supplement: Placebo (Constant Daily Dose)
Identical-appearing placebo capsule consumed at the same times as the caffeine intervention.
Experimental: 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.
Dietary supplement: Caffeine (Escalating Dose)
Oral caffeine starting at 3 mg/kg/day and increasing incrementally to reach 6 mg/kg/day by week 4.
Placebo Comparator: 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.
Dietary supplement: Placebo (Escalating Dose)
Placebo capsule daily for 4 weeks with simulated dose escalation protocol, then crossover to escalating caffeine after 2-week washout.
Experimental: 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.
Dietary supplement: Caffeine (Training Days Only)
Oral caffeine capsule at 3 mg/kg body weight, consumed only on training days approximately 60 minutes before exercise.
Placebo Comparator: 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.
Dietary supplement: Placebo (Training Days Only)
Placebo capsule only on training days for 4 weeks, then crossover to caffeine after 2-week washout.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline; End of Intervention Period 1 (Week 4); End of Intervention Period 2 (Week 4)
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.
Baseline; End of Intervention Period 1 (Week 4); End of Intervention Period 2 (Week 4)
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.
Baseline; End of Intervention Period 1 (Week 4); End of Intervention Period 2 (Week 4)
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.
Baseline; End of Intervention Period 1 (Week 4); End of Intervention Period 2 (Week 4)
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.
Intervention Period 1 (Weeks 1-4); Intervention Period 2 (Weeks 1-4)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Serum Hormonal Concentrations
Time Frame: Baseline; Week 2; End of Intervention Period 1 (Week 4); Baseline; Week 2; End of Intervention Period 2 (Week 4)
Change in serum concentrations of insulin, cortisol, testosterone, and insulin-like growth factor 1 (IGF-1), assessed using standard biochemical analyses.
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
Time Frame: Weekly during Intervention Period 1 (Weeks 1-4); Weekly during Intervention Period 2 (Weeks 1-4)
Self-reported sleep quality total score assessed using validated sleep questionnaires. Higher scores will indicate better sleep quality.
Weekly during Intervention Period 1 (Weeks 1-4); Weekly during Intervention Period 2 (Weeks 1-4)
Subjective Recovery Score Assessed by Likert Scale
Time Frame: After each supervised training session during Intervention Period 1; After each supervised training session during Intervention Period 2
Subjective recovery score assessed using a Likert-type scale following each supervised training session. Higher scores will indicate better perceived recovery.
After each supervised training session during Intervention Period 1; After each supervised training session during Intervention Period 2
Adverse Events
Time Frame: Throughout the entire study duration (8 weeks)
Number and severity of reported adverse events, including palpitations, anxiety, restlessness, insomnia, headache, and gastrointestinal discomfort.
Throughout the entire study duration (8 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Istanbul University - Cerrahpasa

Collaborators

İstanbul Yeni Yüzyıl Üniversitesi

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

February 20, 2026

Primary Completion (Estimated)

April 20, 2026

Study Completion (Estimated)

April 20, 2026

Study Registration Dates

First Submitted

January 30, 2026

First Submitted That Met QC Criteria

February 7, 2026

First Posted (Actual)

February 13, 2026

Study Record Updates

Last Update Posted (Actual)

February 13, 2026

Last Update Submitted That Met QC Criteria

February 7, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2026/01-1792

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All extracted personal data (IPD) from this information will be shared along with supporting data for the publication results. Data dictionaries relating to data settings are also stored.

IPD Sharing Time Frame

Data requests will be accepted 6 months after the article is published; data will be accessible for 36 months.

IPD Sharing Access Criteria

Data sharing requests must be made by researchers with scientific justification and ethical approval. Requests will be evaluated, and those deemed appropriate will be signed with a confidentiality agreement and a data usage agreement. Requests will be received via abdullah.demirli@iuc.edu.tr e-mail address.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ANALYTIC_CODE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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