Resistance Training Adaptations and Caffeine Intake

NCT07410195 | Not Yet Recruiting

• 1 other identifier: 2026/01-1792
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

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.

Conditions

Muscle Hypotrophy; Exercise Performance; Muscle Strength; Adaptation

Keywords

Caffeine; Resistance Training; Muscle Adaptation; Supplementation; Strength Training; Hypertrophy

Outcome Measures

Primary Outcomes (5)

• 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.

  Baseline; End of Intervention Period 1 (Week 4); End of Intervention Period 2 (Week 4)

• 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.

  Baseline; End of Intervention Period 1 (Week 4); End of Intervention Period 2 (Week 4)

• Change in Muscle Volume Measured by DXA

  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

  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

  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 Outcomes (4)

• 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)

Study Arms (6)

Strategy 1: Constant Daily Dose - Caffeine First

EXPERIMENTAL

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)

Strategy 1: Constant Daily Dose - Placebo First

PLACEBO COMPARATOR

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)

Strategy 2: Escalating Dose - Caffeine First

EXPERIMENTAL

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)

Strategy 2: Escalating Dose - Placebo First

PLACEBO COMPARATOR

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)

Strategy 3: Training Days Only - Caffeine First

EXPERIMENTAL

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)

Strategy 3: Training Days Only - Placebo First

PLACEBO COMPARATOR

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)

Interventions

Caffeine (Constant Daily Dose) DIETARY_SUPPLEMENT

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).

Strategy 1: Constant Daily Dose - Caffeine First

Placebo (Constant Daily Dose) DIETARY_SUPPLEMENT

Identical-appearing placebo capsule consumed at the same times as the caffeine intervention.

Strategy 1: Constant Daily Dose - Placebo First

Caffeine (Escalating Dose) DIETARY_SUPPLEMENT

Oral caffeine starting at 3 mg/kg/day and increasing incrementally to reach 6 mg/kg/day by week 4.

Strategy 2: Escalating Dose - Caffeine First

Placebo (Escalating Dose) DIETARY_SUPPLEMENT

Placebo capsule daily for 4 weeks with simulated dose escalation protocol, then crossover to escalating caffeine after 2-week washout.

Strategy 2: Escalating Dose - Placebo First

Caffeine (Training Days Only) DIETARY_SUPPLEMENT

Oral caffeine capsule at 3 mg/kg body weight, consumed only on training days approximately 60 minutes before exercise.

Strategy 3: Training Days Only - Caffeine First

Placebo (Training Days Only) DIETARY_SUPPLEMENT

Placebo capsule only on training days for 4 weeks, then crossover to caffeine after 2-week washout.

Strategy 3: Training Days Only - Placebo First

Eligibility Criteria

• Age: 18 Years - 30 Years
• Gender Eligibility Details: Individuals who were assigned male at birth and identify as male.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Istanbul University - Cerrahpasa: lead
• İstanbul Yeni Yüzyıl Üniversitesi: collaborator

Study Sites (1)

Istanbul University-Cerrahpasa, Faculty of Sport Sciences Performance Laboratory

Istanbul, Avcilar, 34010, Turkey (Türkiye)

Location

Related Publications (7)

• Lovallo WR, Whitsett TL, al'Absi M, Sung BH, Vincent AS, Wilson MF. Caffeine stimulation of cortisol secretion across the waking hours in relation to caffeine intake levels. Psychosom Med. 2005 Sep-Oct;67(5):734-9. doi: 10.1097/01.psy.0000181270.20036.06.

  PMID: 16204431 BACKGROUND

• Matsumura T, Takamura Y, Fukuzawa K, Nakagawa K, Nonoyama S, Tomoo K, Tsukamoto H, Shinohara Y, Iemitsu M, Nagano A, Isaka T, Hashimoto T. Ergogenic Effects of Very Low to Moderate Doses of Caffeine on Vertical Jump Performance. Int J Sport Nutr Exerc Metab. 2023 Jul 26;33(5):275-281. doi: 10.1123/ijsnem.2023-0061. Print 2023 Sep 1.

  PMID: 37414404 BACKGROUND

• Brook MS, Wilkinson DJ, Mitchell WK, Lund JN, Szewczyk NJ, Greenhaff PL, Smith K, Atherton PJ. Skeletal muscle hypertrophy adaptations predominate in the early stages of resistance exercise training, matching deuterium oxide-derived measures of muscle protein synthesis and mechanistic target of rapamycin complex 1 signaling. FASEB J. 2015 Nov;29(11):4485-96. doi: 10.1096/fj.15-273755. Epub 2015 Jul 13.

  PMID: 26169934 BACKGROUND

• Pickering C, Kiely J. Are low doses of caffeine as ergogenic as higher doses? A critical review highlighting the need for comparison with current best practice in caffeine research. Nutrition. 2019 Nov-Dec;67-68:110535. doi: 10.1016/j.nut.2019.06.016. Epub 2019 Jun 26.

  PMID: 31400738 BACKGROUND

• Grgic J, Trexler ET, Lazinica B, Pedisic Z. Effects of caffeine intake on muscle strength and power: a systematic review and meta-analysis. J Int Soc Sports Nutr. 2018 Mar 5;15:11. doi: 10.1186/s12970-018-0216-0. eCollection 2018.

  PMID: 29527137 BACKGROUND

• Guest NS, VanDusseldorp TA, Nelson MT, Grgic J, Schoenfeld BJ, Jenkins NDM, Arent SM, Antonio J, Stout JR, Trexler ET, Smith-Ryan AE, Goldstein ER, Kalman DS, Campbell BI. International society of sports nutrition position stand: caffeine and exercise performance. J Int Soc Sports Nutr. 2021 Jan 2;18(1):1. doi: 10.1186/s12970-020-00383-4.

  PMID: 33388079 BACKGROUND

• Grgic J, Grgic I, Pickering C, Schoenfeld BJ, Bishop DJ, Pedisic Z. Wake up and smell the coffee: caffeine supplementation and exercise performance-an umbrella review of 21 published meta-analyses. Br J Sports Med. 2020 Jun;54(11):681-688. doi: 10.1136/bjsports-2018-100278. Epub 2019 Mar 29.

  PMID: 30926628 BACKGROUND

MeSH Terms

Conditions

Muscular Atrophy; Hypertrophy

Interventions

Caffeine

Condition Hierarchy (Ancestors)

Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Central Study Contacts

Abdullah Demirli, PhD

CONTACT

+90 545 259 22 25; abdullah.demirli@iuc.edu.tr

Kaan Kaya, PhD

CONTACT

+90 546 876 0049; kaan.kaya@yeniyuzyil.edu.tr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: This is a double-blind, placebo-controlled crossover trial with three parallel supplementation strategies. Within each strategy, participants are randomized to receive either caffeine or placebo during the first 4-week intervention period. After a 2-week washout period, participants cross over to the opposite condition (caffeine to placebo or placebo to caffeine) for a second 4-week intervention period. All participants undergo supervised resistance training three times per week throughout both intervention periods. The three supplementation strategies are tested independently: (1) constant daily dosing, (2) escalating dose, and (3) training-day-only dosing.

Study Record Dates

• First Submitted: January 30, 2026
• First Posted: February 13, 2026
• Study Start: February 20, 2026
• Primary Completion: April 20, 2026
• Study Completion: April 20, 2026
• Last Updated: February 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Data requests will be accepted 6 months after the article is published; data will be accessible for 36 months.
• 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.

Locations

TU (1)