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

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
180

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Istanbul University - Cerrahpasa

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 20, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 20, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 20, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 30, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 7, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 13, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 13, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 7, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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