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| Name | Class |
|---|---|
| İstanbul Yeni Yüzyıl Üniversitesi | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| 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. |
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| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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). |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline; Week 2; End of Intervention Period 1 (Week 4); Baseline; Week 2; End of Intervention Period 2 (Week 4) |
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Inclusion Criteria:
Exclusion Criteria:
Individuals who were assigned male at birth and identify as male.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| 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 |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Istanbul University-Cerrahpasa, Faculty of Sport Sciences Performance Laboratory | Istanbul | Avcilar | 34010 | Turkey (Türkiye) |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16204431 | Background | 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. | |
| 37414404 | 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. |
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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.
Data requests will be accepted 6 months after the article is published; data will be accessible for 36 months.
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.
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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.
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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.
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| 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. |
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| 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. |
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| Placebo (Constant Daily Dose) | Dietary Supplement | Identical-appearing placebo capsule consumed at the same times as the caffeine intervention. |
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| 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. |
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| 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. |
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| 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. |
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| Placebo (Training Days Only) | Dietary Supplement | Placebo capsule only on training days for 4 weeks, then crossover to caffeine after 2-week washout. |
|
| Self-Reported Sleep Quality Score |
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 | 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 | Number and severity of reported adverse events, including palpitations, anxiety, restlessness, insomnia, headache, and gastrointestinal discomfort. | Throughout the entire study duration (8 weeks) |
| 26169934 | 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. |
| 31400738 | 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. |
| 29527137 | 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. |
| 33388079 | 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. |
| 30926628 | 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. |
| ID | Term |
|---|---|
| D009133 | Muscular Atrophy |
| D006984 | Hypertrophy |
| ID | Term |
|---|---|
| D020879 | Neuromuscular Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D001284 | Atrophy |
| D020763 | Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012816 | Signs and Symptoms |
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| ID | Term |
|---|---|
| D002110 | Caffeine |
| ID | Term |
|---|---|
| D014970 | Xanthines |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D011688 | Purinones |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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