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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Dietary Exposure

Intervention / Treatment
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* Dietary Supplement: Dietary Supplement
* Behavioral: Endurance exercise on a cycle ergometer


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Investigator)
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: L-arginine and L-citrulline<br>10 days of supplementation with 1.5 g of L-arginine and 1.5 g of L-citrulline per day | Dietary Supplement: Dietary Supplement<br>* 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.<br>Behavioral: Endurance exercise on a cycle ergometer<br>* On day 10 of each supplementation period, subjects will complete a performance test on a cycle ergometer to investigate their endurance performance.<br>|
| Experimental: L-arginine<br>10 days of supplementation with 3 g of L-arginine per day | Dietary Supplement: Dietary Supplement<br>* 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.<br>Behavioral: Endurance exercise on a cycle ergometer<br>* On day 10 of each supplementation period, subjects will complete a performance test on a cycle ergometer to investigate their endurance performance.<br>|
| Placebo Comparator: Placebo (corn-starch)<br>10 days of supplementation with corn-starch | Dietary Supplement: Dietary Supplement<br>* 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.<br>Behavioral: Endurance exercise on a cycle ergometer<br>* On day 10 of each supplementation period, subjects will complete a performance test on a cycle ergometer to investigate their endurance performance.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Endurance performance on a cycle ergometer between L-arginine supplementation and placebo supplementation | 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 | 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 | 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 | 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of amino acid and nitric oxide biomarkers levels in plasma between L-arginine supplementation and placebo supplementation | 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 | 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 | 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 | 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 | 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 | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endurance performance, Mitochondrial function, L-arginine, L-citrulline, Healthy males