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

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: Completed
• Conditions: Healthy Volunteers; Cognitive Performance; Anaerobic Performance
• Intervention / Treatment: Other: Placebo; Dietary supplement: Creatine Monohydrate; Dietary supplement: L-Arginine

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: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• 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

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

Outcome Measure	Measure Description	Time Frame
RAST Average Power	Average power during the Running-Based Anaerobic Sprint Test following acute supplementation.	60 minutes after supplementation, during the testing session
RAST Peak Power	Peak power during the Running-Based Anaerobic Sprint Test following acute supplementation.	60 minutes after supplementation, during the testing session
Countermovement Jump Height	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	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

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

Collaborators and Investigators

• Sponsor: Inonu University
• Collaborators: Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia

Publications and helpful links

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

Study Major Dates

• Study Start (Actual): April 1, 2025
• Primary Completion (Actual): May 15, 2025
• Study Completion (Actual): May 16, 2025

Study Registration Dates

• First Submitted: April 14, 2026
• First Submitted That Met QC Criteria: April 21, 2026
• First Posted (Actual): April 23, 2026

Study Record Updates

• Last Update Posted (Actual): April 23, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Creatine; L-Arginine; Reaction Time; Stroop Test; Dietary Supplementation; Countermovement Jump; Crossover Trial; Running-Based Anaerobic Sprint Test; Recreational Athletes
• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Organic Chemicals; Amino Acids; Amino Acids, Basic; Amino Acids, Diamino; Amino Acids, Essential; Guanidines; Amidines; Arginine; Creatine
• Other Study ID 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