Acute Effects of Creatine and L-Arginine Co-Supplementation on Anaerobic and Cognitive Performance in Recreationally Active Males

April 21, 2026 updated by: Assoc. Prof. Dr. Özgür EKEN, Inonu University

Acute Effects of Creatine and L-Arginine Co-Supplementation on Anaerobic Power, Jump Performance, and Cognitive Reaction Time in Recreationally Active Males: A Randomized Crossover Trial

This randomized, double-blind, four-period crossover trial investigates the acute effects of creatine monohydrate, L-arginine, and their combined administration on anaerobic performance, jump performance, and cognitive reaction time in recreationally active adult males. Eighteen healthy male participants complete four experimental conditions in randomized order: placebo, creatine, L-arginine, and creatine plus L-arginine, with at least 72 hours between sessions. Sixty minutes after supplementation, participants perform the Stroop Color-Word Test, countermovement jump test, and Running-Based Anaerobic Sprint Test. Primary outcomes include peak power, average power, countermovement jump height, and incongruent Stroop reaction time. The study aims to determine whether acute co-supplementation produces greater ergogenic and cognitive benefits than either supplement alone or placebo.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

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

Creatine monohydrate and L-arginine are widely used ergogenic supplements that may influence performance through different physiological mechanisms. Creatine contributes to rapid adenosine triphosphate resynthesis through phosphocreatine availability, whereas L-arginine serves as a precursor for nitric oxide synthesis and may enhance blood flow and substrate delivery during exercise. Their combined administration may therefore produce complementary effects on physical and cognitive performance.

This study uses a randomized, double-blind, four-treatment crossover design in recreationally active adult males. Each participant completes four conditions: placebo, creatine monohydrate, L-arginine, and combined creatine plus L-arginine. Sessions are separated by at least 72 hours, and all testing is conducted at the same time of day. Supplementation is administered 60 minutes before performance testing. Creatine is provided as a single acute dose of 0.3 g/kg, L-arginine as 6 g, and the placebo as a matched control beverage.

Outcome assessments include the Running-Based Anaerobic Sprint Test for repeated-sprint power, the countermovement jump test for explosive lower-body performance, and the Stroop Color-Word Test for cognitive reaction time and accuracy. The primary objective is to examine whether acute co-supplementation with creatine and L-arginine improves anaerobic and cognitive outcomes more than placebo or either supplement alone.

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 (Actual)

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.
18

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 Locations

  • Turkey (Türkiye)
    • Malatya
      • Malatya, Malatya, Turkey (Türkiye), 44280
        • Inonu University, Faculty of Sport Sciences

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 recreational athletes aged 18 years or older
  • At least 2 years of regular participation in organized sport
  • Apparently healthy and able to complete high-intensity exercise testing

Exclusion Criteria:

  • Known orthopedic, neurological, cardiovascular, pulmonary, or metabolic disorders
  • Use of anabolic steroids or performance-enhancing drugs within the previous 3 months
  • Use of psychoactive or stimulant substances during the study

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: Double

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.
Placebo Comparator: Placebo
Participants received 6 g sucrose dissolved in 250 mL of water as the placebo condition.
Other: Placebo
Placebo beverage containing 6 g sucrose dissolved in 250 mL of water.
Experimental: Creatine
Participants received a single acute dose of creatine monohydrate at 0.3 g/kg dissolved in 250 mL of water.
Dietary supplement: Creatine Monohydrate
Acute oral creatine monohydrate supplementation at 0.3 g/kg body mass.
Experimental: L-Arginine
Participants received a single acute dose of 6 g L-arginine dissolved in 250 mL of water.
Dietary supplement: L-Arginine
Acute oral L-arginine supplementation at a dose of 6 g.
Experimental: Creatine + L-Arginine
Participants received combined acute supplementation with creatine monohydrate at 0.3 g/kg plus 6 g L-arginine in 250 mL of water.
Dietary supplement: Creatine Monohydrate
Acute oral creatine monohydrate supplementation at 0.3 g/kg body mass.
Dietary supplement: L-Arginine
Acute oral L-arginine supplementation at a dose of 6 g.

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
RAST Average Power
Time Frame: 60 minutes after supplementation, during the testing session
Average power during the Running-Based Anaerobic Sprint Test following acute supplementation.
60 minutes after supplementation, during the testing session
RAST Peak Power
Time Frame: 60 minutes after supplementation, during the testing session
Peak power during the Running-Based Anaerobic Sprint Test following acute supplementation.
60 minutes after supplementation, during the testing session
Countermovement Jump Height
Time Frame: 60 minutes after supplementation, during the testing session
Best countermovement jump height measured using the Optojump system following acute supplementation.
60 minutes after supplementation, during the testing session
Stroop Incongruent Median Reaction Time
Time Frame: 60 minutes after supplementation, during the testing session
Median reaction time in the incongruent condition of the computerized Stroop Color-Word Test following acute supplementation.
60 minutes after supplementation, during the testing session

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
RAST Minimum Power
Time Frame: 60 minutes after supplementation, during the testing session
Minimum power during the Running-Based Anaerobic Sprint Test following acute supplementation.
60 minutes after supplementation, during the testing session
RAST Fatigue Index
Time Frame: 60 minutes after supplementation, during the testing session
Fatigue index during the Running-Based Anaerobic Sprint Test following acute supplementation.
60 minutes after supplementation, during the testing session

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.
Inonu University

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.
Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia

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

  • d'Unienville NMA, Blake HT, Coates AM, Hill AM, Nelson MJ, Buckley JD. Effect of food sources of nitrate, polyphenols, L-arginine and L-citrulline on endurance exercise performance: a systematic review and meta-analysis of randomised controlled trials. J Int Soc Sports Nutr. 2021;18:76. https://doi.org/10.1186/s12970-021-00472-y
  • Nyawose S, Naidoo R, Naumovski N, McKune AJ. The Effects of Consuming Amino Acids L-Arginine, L-Citrulline (and Their Combination) as a Beverage or Powder, on Athletic and Physical Performance: A Systematic Review. Beverages. 2022;8:48. https://doi.org/10.3390/beverages8030048
  • Meixner B, Stegmaier J, Renner P, Koehler K, Yang W-H, Sperlich B. Supplementation of Creatine Monohydrate Improves Sprint Performance but Has no Effect on Glycolytic Contribution: A Nonrandomized, Placebo-Controlled Crossover Trial in Trained Cyclists. Curr Dev Nutr. 2025;9:104561. https://doi.org/10.1016/j.cdnut.2025.104561
  • Vargas-Molina S, García-Sillero M, Kreider RB, Salinas E, Petro JL, Benítez-Porres J, et al. A randomized open-labeled study to examine the effects of creatine monohydrate and combined training on jump and scoring performance in young basketball players. J Int Soc Sports Nutr. 2022;19:529-42. https://doi.org/10.1080/15502783.2022.2108683
  • Fernández-Landa J, Santibañez-Gutierrez A, Todorovic N, Stajer V, Ostojic SM. Effects of Creatine Monohydrate on Endurance Performance in a Trained Population: A Systematic Review and Meta-analysis. Sports Medicine. 2023;53:1017-27. https://doi.org/10.1007/s40279-023-01823-2
  • Kerksick CM, Wilborn CD, Roberts MD, Smith-Ryan A, Kleiner SM, Jäger R, et al. ISSN exercise & sports nutrition review update: research & recommendations. J Int Soc Sports Nutr. 2018;15. https://doi.org/10.1186/s12970-018-0242-y

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 (Actual)

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.
April 1, 2025

Primary Completion (Actual)

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.
May 15, 2025

Study Completion (Actual)

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.
May 16, 2025

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).
April 14, 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.
April 21, 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.
April 23, 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.
April 23, 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.
April 21, 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.
April 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.
  • INU-CRLA-2025-01
  • Approval No: 2025/6879 (Other Identifier: Inonu University)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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