Resistance Training Adaptations and Caffeine Intake

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

This parallel-group, randomized, double-blind, placebo-controlled trial investigates the effects of three different caffeine supplementation strategies on resistance training-induced adaptations in 120 caffeine-naive, inactive young adult males. Participants will undergo a 10-week supervised resistance training program. The four supplementation strategies are: (1) constant daily low-moderate dosing (4 mg/kg/day), (2) gradually escalating dose (2 to 6 mg/kg across weeks), (3) training-day-only caffeine (4 mg/kg/day), and (4) placebo. Primary outcomes include maximal strength, body composition (lean body mass and fat mass), skeletal muscle thickness, and training volume progression. Secondary outcomes include muscular endurance, jump height, flight-time-to-contraction-time (FT:CT) ratio, mechanistic/biological variables (epinephrine, norepinephrine, cortisol, testosterone, creatine kinase, IGF-1), rate of perceived exertion, sleep/recovery parameters, and adverse effects.

Study Overview

• Status: Completed
• Conditions: Muscle Strength; Exercise Performance; Adaptation; Muscle Hypotrophy
• Intervention / Treatment: Dietary supplement: Caffeine (Constant Daily Dose); Dietary supplement: Caffeine (Escalating Dose); Dietary supplement: Caffeine (Training Days Only); Dietary supplement: placebo capsule

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 2-6 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: 120 caffeine-naive, physically inactive young adult males aged 18-30 years will be randomly assigned to one of the following groups (n=30 per group): (1) constant daily low-moderate dosing (CON, 4 mg/kg/day), (2) gradually escalating dose (ESC, 2 to 6 mg/kg across weeks), (3) training-day-only caffeine (TDO, 4 mg/kg/day), and (4) placebo (PLA). All participants will undergo supervised resistance training 3 times per week. OUTCOMES: Primary endpoints include maximal strength, body composition (lean body mass and fat mass), skeletal muscle thickness, and training volume metrics. Secondary outcomes include muscular endurance, jump height, flight-time-to-contraction-time (FT:CT) ratio, mechanistic/biological variables (epinephrine, norepinephrine, cortisol, testosterone, creatine kinase, IGF-1), rate of perceived exertion, sleep/recovery parameters, and adverse effects. STATISTICAL ANALYSIS: Linear Mixed Models will be used to analyze the data.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male sex and age between 18 and 30 years
• Daily caffeine intake <100 mg/day
• resistance-training experience ≥1 year and <3 years
• Body mass index (BMI) between 18.5-25 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 or blood sampling

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Strategy 1: Constant Daily Dose; Participants receive caffeine at a constant daily dose of 4 mg/kg/day for 10 weeks. Supervised resistance training is performed 3 times per week for 10 weeks.	Dietary supplement: Caffeine (Constant Daily Dose); Oral caffeine capsule at 4 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).
Experimental: Strategy 2: Escalating Dose; Participants receive caffeine at a gradually escalating dose, starting at 2 mg/kg/day in week 1 and increasing to 6 mg/kg/day by week 10 (1 mg/kg every 2 weeks). Supervised resistance training is performed 3 times per week for 10 weeks.	Dietary supplement: Caffeine (Escalating Dose); • Oral caffeine starting at 2 mg/kg/day and increasing incrementally to reach 6 mg/kg/day by week 10.
Experimental: Strategy 3: Training Days Only; Participants receive caffeine at 4 mg/kg only on training days (3 times per week) for 10 weeks. Supervised resistance training is performed 3 times per week for 10 weeks.	Dietary supplement: Caffeine (Training Days Only); Oral caffeine capsule at 4 mg/kg body weight, consumed only on training days approximately 60 minutes before exercise.
Placebo Comparator: Placebo; Participants receive 250 mg/day cellulose for 10 weeks. Supervised resistance training is performed 3 times per week for 10 weeks.	Dietary supplement: placebo capsule; Oral placebo capsule (250 mg cellulose), consumed daily approximately 60 minutes before training sessions (on training days) or at the same time of day (on rest days).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 and post-test (after completing 10 weeks of interventions)
Change in Fat Mass Measured by DXA	Change in fat mass measured using DXA.	Baseline and post-test (after completing 10 weeks of interventions)
Maximal Strength	Measure by one-repetition maximum (1-RM) on a lower body (Smith machine Back Squat) and two upper body (Bench Press machine and Lat Pulldown machine) exercises.	Baseline, and post-test (after completing 10 weeks of interventions)
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.	During the intervention period (all training sessions).
Change in Skeletal Muscle Thickness	Change in skeletal muscle thickness measured using B-mode ultrasound, reported in mm.	Baseline and post-test (after completing 10 weeks of interventions)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscular endurance	It will be measured by a repetitions-to-failure test on the Smith machine back squat using a load corresponding to 60% of the current 1RM.	Baseline, and post-test (after completing 10 weeks of interventions)
Neuromuscular function	It will be measured by the countermovement jump (CMJ) test on a force platform.	Baseline and post-test (after completing 10 weeks of interventions)
Resting concentrations of testosterone	They will be measured using standard biochemical analyses.	Baseline, and post-test (after completing 10 weeks of interventions)
Plasma epinephrine responses to exercise	They will be measured using standard biochemical analyses.	During the first training session of Week 1 and the final training session of Week 10, at three time points: (1) pre-supplementation, (2) immediately before exercise and (3) immediately after exercise.
Recovery	It will be assessed using the validated 0-10 Perceived Recovery Status Scale (0 to 2: very poorly recovered, 3 to 4: poorly recovered, 5 to 6: adequately recovered, 7 to 8: well recovered, and 9 to 10: fully recovered).	Before each of the 30 training sessions during the study.
Adverse Events	Adverse events will be assessed using a standardized questionnaire administered throughout the study.	From initiation of the 4-week caffeine abstinence period through completion of the post-intervention assessments, monitored throughout the study (approximately 16 weeks).
Sleep quality	It will be assessed by the Pittsburgh Sleep Quality Index (PSQI).	Baseline and post-test (after completing 10 weeks of interventions).
Rate of perceived exertion	Assessed using the Borg Category-Ratio (CR10) Scale, ranging from 0 ("nothing at all") to 10 ("maximal"). Participants will report their perceived exertion after each supervised training session.	After each supervised training session, participants were assessed throughout the 10-week intervention period (30 training sessions).
Resting concentrations of insulin-like growth factor-1 (IGF-1)	They will be measured using standard biochemical analyses.	Baseline, and post-test (after completing 10 weeks of interventions)
Resting concentrations of cortisol	They will be measured using standard biochemical analyses.	Baseline, and post-test (after completing 10 weeks of interventions)
Resting concentrations of creatine kinase	They will be measured using standard biochemical analyses.	Baseline, and post-test (after completing 10 weeks of interventions)
Serum cortisol responses to exercise	They will be measured using standard biochemical analyses.	During the first training session of Week 1 and the final training session of Week 10, at three time points: (1) pre-supplementation, (2) immediately before exercise and (3) immediately after exercise.
Plasma norepinephrine responses to exercise	They will be measured using standard biochemical analyses.	During the first training session of Week 1 and the final training session of Week 10, at three time points: (1) pre-supplementation, (2) immediately before exercise and (3) immediately after exercise.

Collaborators and Investigators

• Sponsor: Istanbul University - Cerrahpasa
• Collaborators: İstanbul Yeni Yüzyıl Üniversitesi

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2026
• Primary Completion (Actual): May 30, 2026
• Study Completion (Actual): June 7, 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): July 14, 2026
• Last Update Submitted That Met QC Criteria: July 12, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Supplementation; Resistance Training; Hypertrophy; Caffeine; Strength Training; Muscle Adaptation
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Atrophy; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hypertrophy; Muscular Atrophy; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Alkaloids; Purinones; Purines; Xanthines; Caffeine
• 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