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Completed

NCT Number: NCT03998800

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

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Key information

Conditions

Dietary Exposure

Age range

18 year–40 year

Sex eligibility

Male

Study type

Interventional

Phase

Not applicable

Primary location

School of Sport, Exercise and Health Sciences

Loughborough, Leicester, Le11 3YU, United Kingdom

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

Endurance exercise on a cycle ergometer

Behavioral

On day 10 of each supplementation period, subjects will complete a performance test on a cycle ergometer to investigate their endurance performance.

Primary outcomes

  1. 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

  2. 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

  3. 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.

  4. 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.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

Sponsors and collaborators

Lead sponsor

Loughborough University

Other

Collaborators

  • Kyowa Hakko Bio Co., Ltd.

Registry information

Official study title

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

Important dates

Study start
2019
Primary completion
2022
Study completion
2022
First posted
Jun 26, 2019
Registry last updated
May 2, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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