Effects of L-arginine and L-citrulline Supplementation on Muscle Respiration

April 29, 2022 updated by: Stephen Bailey, Loughborough University

The Effect of L-arginine and L-citrulline Supplementation on Endurance Performance and Mitochondrial Respiration

The objective of this trial is to determine the effects of dietary supplementation with the amino acids, L-arginine and L-citrulline, on endurance performance and mitochondrial respiration in healthy men compared to supplementation with L-arginine alone and a placebo supplement.

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

This study is a randomized, double-blind, cross over trial of L-arginine and L-citrulline supplementation, L-arginine supplementation alone and placebo supplementation in healthy men. The intervention period will be 8-11 weeks for each participant and a minimum of 15 individuals will be recruited and enrolled to complete the trial. Subjects will complete the experimental protocol described below over 3 individual 10 day supplementation periods, separated by washout periods of approximately 2 weeks. Subjects will ingest corn-starch as a placebo, L-arginine (3g/day) or L-arginine (1.5 g/day) + L-citrulline (1.5g/day). On day 7 of the supplementation period, a skeletal muscle biopsy and blood sample will be obtained from the subjects to investigate mitochondrial function and blood amino acid and nitric oxide levels. On day 10 of the supplementation period, subjects will complete a performance test on a cycle ergometer to investigate their endurance performance. These assessments will be performed to determine the effects of co-ingesting L-arginine and L-citrulline compared to L-arginine alone and placebo administration.

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

  • United Kingdom
    • Leicester
      • Loughborough, Leicester, United Kingdom, Le11 3YU
        • School of Sport, Exercise and Health 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

18 years to 40 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • healthy male, 18-40 years of age
  • recreationally-active
  • healthy BMI (≥18.5 and ≤24.9 kg/m2)

Exclusion Criteria:

  • participating in other studies currently or in the past two months or has an intention to participate in other studies over the period of this study
  • history of gastric, digestive, cardiovascular, renal disease or any other orthopaedic diseases related to motor organs
  • lidocaine allergy
  • use of medication that may affect study measures
  • contraindication to the biopsy procedures
  • on medications that affect the immune system
  • on Aspirin or other drugs known to prolong bleeding
  • smoker
  • user of dietary supplements currently or in the past one month
  • a heavy drinker

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.
Experimental: L-arginine and L-citrulline
10 days of supplementation with 1.5 g of L-arginine and 1.5 g of L-citrulline per day
Dietary supplement: Dietary Supplement
Dietary Supplement: L-arginine and L-citrulline supplement, L-arginine supplement, or placebo supplement (corn-starch) Subjects will complete 3 individual 10 day supplementation periods, separated by washout periods of approximately 2 weeks.
Behavioral: Endurance exercise on a cycle ergometer
On day 10 of each supplementation period, subjects will complete a performance test on a cycle ergometer to investigate their endurance performance.
Experimental: L-arginine
10 days of supplementation with 3 g of L-arginine per day
Dietary supplement: Dietary Supplement
Dietary Supplement: L-arginine and L-citrulline supplement, L-arginine supplement, or placebo supplement (corn-starch) Subjects will complete 3 individual 10 day supplementation periods, separated by washout periods of approximately 2 weeks.
Behavioral: Endurance exercise on a cycle ergometer
On day 10 of each supplementation period, subjects will complete a performance test on a cycle ergometer to investigate their endurance performance.
Placebo Comparator: Placebo (corn-starch)
10 days of supplementation with corn-starch
Dietary supplement: Dietary Supplement
Dietary Supplement: L-arginine and L-citrulline supplement, L-arginine supplement, or placebo supplement (corn-starch) Subjects will complete 3 individual 10 day supplementation periods, separated by washout periods of approximately 2 weeks.
Behavioral: Endurance exercise on a cycle ergometer
On day 10 of each supplementation period, subjects will complete a performance test on a cycle ergometer to investigate their endurance performance.

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
Change in Endurance performance on a cycle ergometer between L-arginine supplementation and placebo supplementation
Time Frame: 8-11 weeks
On day 10 of the supplementation periods, subjects will complete a performance test on a cycle ergometer to investigate their endurance performance
8-11 weeks
Change in Endurance performance on a cycle ergometer between L-arginine + L-citrulline supplementation and placebo supplementation
Time Frame: 8-11 weeks
On day 10 of the supplementation periods, subjects will complete a performance test on a cycle ergometer to investigate their endurance performance
8-11 weeks
Changes of mitochondrial function in skeletal muscle between L-arginine supplementation and placebo supplementation
Time Frame: 8-11 weeks
On day 7 of the supplementation periods, a skeletal muscle biopsy sample will be obtained from subjects to investigate mitochondrial function.
8-11 weeks
Changes of mitochondrial function in skeletal muscle between L-arginine + L-citrulline supplementation and placebo supplementation
Time Frame: 8-11 weeks
On day 7 of the supplementation periods, a skeletal muscle biopsy sample will be obtained from subjects to investigate mitochondrial function.
8-11 weeks

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
Changes of amino acid and nitric oxide biomarkers levels in plasma between L-arginine supplementation and placebo supplementation
Time Frame: 8-11 weeks
On days 7 and 10 of the supplementation periods, a venous blood sample will be obtained from subjects to investigate amino acid and nitric oxide biomarkers levels in plasma.
8-11 weeks
Changes of amino acid and nitric oxide biomarkers levels in plasma between L-arginine + L-citrulline supplementation and placebo supplementation
Time Frame: 8-11 weeks
On days 7 and 10 of the supplementation periods, a venous blood sample will be obtained from subjects to investigate amino acid and nitric oxide biomarkers levels in plasma.
8-11 weeks
Changes in muscle oxygenation between L-arginine supplementation and placebo supplementation
Time Frame: 8-11 weeks
On day 10 of the supplementation periods, skeletal muscle oxygenation will be assessed using near-infrared spectroscopy to reveal the tissue saturation index during exercise.
8-11 weeks
Changes in muscle oxygenation between L-arginine + L-citrulline supplementation and placebo supplementation
Time Frame: 8-11 weeks
On day 10 of the supplementation periods, skeletal muscle oxygenation will be assessed using near-infrared spectroscopy to reveal the tissue saturation index during exercise.
8-11 weeks
Changes in subjective feeling during and after exercise between L-arginine supplementation and placebo supplementation
Time Frame: 8-11 weeks
On day 10 of the supplementation period, subjective feeling during (using the 6-20 ratings of perceived exertion scale) and after (using a 100 mm visual analogue scale where 0 mm = no pain and 100 m = maximal pain) exercise will be assessed. Subjective feeling will also be assessed on the morning of day 11 of each supplementation period.
8-11 weeks
Changes in subjective feeling during and after exercise between L-arginine + L-citrulline supplementation and placebo supplementation
Time Frame: 8-11 weeks
On day 10 of the supplementation period, subjective feeling during (using the 6-20 ratings of perceived exertion scale) and after (using a 100 mm visual analogue scale where 0 mm = no pain and 100 m = maximal pain) exercise will be assessed. Subjective feeling will also be assessed on the morning of day 11 of each supplementation period.
8-11 weeks

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.
Loughborough 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.
Kyowa Hakko Bio Co., Ltd.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Stephen J Bailey, PhD, lecturer

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.
May 1, 2019

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.
January 1, 2022

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.
January 1, 2022

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).
June 18, 2019

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.
June 25, 2019

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.
June 26, 2019

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.
May 2, 2022

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 29, 2022

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, 2022

More Information

Terms related to this study

Keywords

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.
  • R19-P010

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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