Combined effects of creatine and paracetamol on muscular performance, fatigue, and recovery in resistance-trained athletes

To investigate the combined effects of creatine monohydrate and paracetamol supplementation on muscular performance, fatigue reduction, and recovery improvement in male athletes

Controlled, parallel-group, double-blind, randomized, phase 3 clinical trial on 30 athletes. Block randomization was performed using Random Allocation Software.

This randomized, double-blind clinical trial was conducted at the gymnasium of Islamic Azad University, Ilkhichi Branch. Assessments included muscle performance, fatigue, and recovery at baseline and week 8. Blinding was performed for participants and outcome assessors using placebos with identical appearance, color, and taste.

Inclusion criteria: Healthy male athletes aged 18 to 30 years; at least 3 years of regular specialized training experience in endurance or strength sports; absence of chronic or acute diseases. Exclusion criteria: History of acute musculoskeletal injury in the past 6 months; use of creatine supplements, paracetamol, steroids, or interfering drugs/supplements in the past 3 months.

Intervention Group: Daily oral creatine monohydrate supplementation (Karen Pharma) for 8 weeks (5-day loading at 20 g/day, 35-day maintenance at 5 g/day) plus 500 mg paracetamol (Amin Pharma) 1 hour pre-exercise, alongside resistance training (8 weeks, 3 sessions/week). Control Group: Identical placebos (Amin Pharma) with the identical training protocol.

Maximal muscular strength (1RM), muscular fatigue index, delayed onset muscle soreness (DOMS), and serum creatine kinase (CK) level

Participants were allocated to the study groups (15 in the experimental group and 15 in the control group) using the balanced block randomization method with variable block sizes of 2 and 4. The randomization sequence was generated using Random Allocation Software (version 2.0.0). To ensure allocation concealment, the generated sequences were placed in sequentially numbered, opaque, sealed envelopes (SNOSE) by a third party who was not involved in the study. Envelopes were opened sequentially only after the completion of baseline assessments at the time of each participant's definitive entry into the study, ensuring that the investigator responsible for enrollment and assessment remained blinded to the group assignment until the last moment.

This is a double-blind trial. Participants, principal investigator, care providers, outcome assessors, and data analysts are blinded to group allocation. Placebos match active supplements in appearance, color, taste, smell, and packaging, prepared, coded, and distributed by an independent third party. Emergency unblinding is available via study physician and ethics committee if needed.

Due to ethical considerations and the need to protect participant confidentiality, as well as the absence of explicit informed consent for sharing individual data, there is no plan to share IPD. Additionally, resources for complete data anonymization are not available.

De-identified Individual Participant Data (IPD) will be made available after study completion and publication of the main article. Includes demographic data, primary outcomes, and laboratory results. Exact repository and timeline have not been finalized yet.

6 months after publication of the main article in a peer-reviewed scientific journal.

Academic and scientific researchers upon written request and approval by the study ethics committee.

For non-commercial scientific research, meta-analyses, and studies related to muscular performance, fatigue, and recovery. Use is permitted only with proper citation of the original study and under a signed data use agreement.

To access non-confidential data and the data dictionary, submit a written request to the corresponding author via email (mjourkesh@ut.ac.ir). Data will be available via Figshare after ethics committee approval.

Requests for access to the study protocol must be submitted in writing via email to the principal investigator (principal investigator’s email address), including the purpose of use. The research team will review the request within 10 working days and provide the protocol if approved.