- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05143879
Long-Term Effect of Combined Citrulline and Nitrate-Rich Beetroot Extract Supplementation
November 21, 2021 updated by: Jose Burgos Balmaseda, Burgos Nutrition
Long-term Effect of Combined Citrulline and Nitrate-rich Beetroot Extract Supplementation on Recovery Status in Trained Male Triathletes
Citrulline (CIT) and nitrate-rich beetroot extract (BEET) are widely studied ergogenic aids.
However, both supplements have been studied in sort-term and isolated.
To the best of the authors' knowledge, the effects of combining both supplements on exercise-induced muscle damage (EIMD) and hormone status have not been investigated to date.
Therefore, the main purpose of this study was to determine the effect and degree of potentiation of the long-term (9 weeks) mixture of 3 g/day of CIT plus 2.1 g/day of BEET (300 mg/day of NIT) supplementation on EIMD markers (urea, creatinine, AST, ALT, GGT, LDH and CK) and anabolic/catabolic hormone status (testosterone, cortisol and Testosterone cortisol ratio (T/C)) in male trained triathletes.
This study was a double-blind, placebo-controlled trial where participants (n = 32) were randomized into 4 different groups: placebo group (PLG; n = 8), CIT group (CITG; 3 g/day of CIT; n = 8), BEET group (BEETG; 2.1 g/day of BEET (300 mg/day of NIT) ; n = 8) and CIT-NIT group (CIT-BEETG; 3 g/day of CIT plus 2.1 g/day of BEET (300 mg/day of NIT); n = 8).
Blood samples were collected from all participants at baseline (T1) and after 9 weeks of supplementation (T2).
Study Overview
Status
Completed
Conditions
Detailed Description
Triathlon is an endurance sport in which athletes compete sequentially in swimming, cycling and running.
Prolonged and strenuous training combined with insufficient recovery can produce muscular and metabolic stress, resulting in structural and functional damage to the musculoskeletal system leading to a fatigue status, which results in decreased athletic performance.
As a consequence of this type of combined exercise, there are also alterations in biochemical markers of exercise-induced muscle damage (EIMD) as well as anabolic/catabolic hormones.
Therefore, their analysis is useful in determining the balance between training loads and recovery.
In this sense, it is essential to include different strategies to reduce or prevent EIMD, which delay or reduce muscle fatigue and improve sports performance.
One of these strategies is the use of different ergogenic aids such as L-citrulline (CIT) and nitrates (NIT) which have been proposed as both substances produce an increase in nitric oxide (NO).
Study Type
Interventional
Enrollment (Actual)
32
Phase
- 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
-
-
Castilla Y León
-
León, Castilla Y León, Spain, 24004
- University of León
-
-
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
Ages Eligible for Study
25 years to 35 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Male
Description
Inclusion Criteria:
- Males between 25 and 35 years old
- Triathletes
- With at least 5 years of experience
- Without any disease
- Non smokers
- Non drinkers of alcohol
- Not to take any other medications or stimulant substances during the study
- 2 weeks without taking other nutritional supplements
Exclusion Criteria:
- Exclusion criteria:
- Men under 25 and over 35 years of age.
- Non triathletes
- Less than 5 years of experience
- With any disease
- Smokers
- Alcohol drinkers
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: Other
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
8 subjects took 3 g/kg/day of placebo during 9 weeks
|
3 g/day during 9 weeks
Other Names:
|
Active Comparator: Nitrate
8 subjects took 3 g/kg/day of nitrate during 9 weeks
|
300 mg/day during 9 weeks
|
Active Comparator: Citrulline
8 subjects took 3 g/kg/day of citrulline during 9 weeks
|
3 g/day during 9 weeks
|
Active Comparator: Nitrate plus Citrulline
8 subjects took 3 g/kg/day of nitrate plus citrulline during 9 weeks
|
3 g/day of citrulline and 300 mg/day of nitrate during 9 weeks
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cortisol
Time Frame: 9 weeks
|
μg/dL
|
9 weeks
|
Testosterone
Time Frame: 9 weeks
|
ng/mL
|
9 weeks
|
Testosterone to cortisol ratio
Time Frame: 9 weeks
|
ng/mL
|
9 weeks
|
Urea
Time Frame: 9 weeks
|
mg/dl
|
9 weeks
|
Creatinine
Time Frame: 9 weeks
|
mg/dl
|
9 weeks
|
AST
Time Frame: 9 weeks
|
U/L
|
9 weeks
|
ALT
Time Frame: 9 weeks
|
U/L
|
9 weeks
|
GGT
Time Frame: 9 weeks
|
U/L
|
9 weeks
|
LDH
Time Frame: 9 weeks
|
U/L
|
9 weeks
|
CK
Time Frame: 9 weeks
|
U/L
|
9 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Jose Burgos Balmaseda, Graduate, University of León
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
- Gonzalez AM, Trexler ET. Effects of Citrulline Supplementation on Exercise Performance in Humans: A Review of the Current Literature. J Strength Cond Res. 2020 May;34(5):1480-1495. doi: 10.1519/JSC.0000000000003426.
- Gilligan DM, Panza JA, Kilcoyne CM, Waclawiw MA, Casino PR, Quyyumi AA. Contribution of endothelium-derived nitric oxide to exercise-induced vasodilation. Circulation. 1994 Dec;90(6):2853-8. doi: 10.1161/01.cir.90.6.2853.
- Anderson JE. A role for nitric oxide in muscle repair: nitric oxide-mediated activation of muscle satellite cells. Mol Biol Cell. 2000 May;11(5):1859-74. doi: 10.1091/mbc.11.5.1859.
- Bailey SJ, Blackwell JR, Lord T, Vanhatalo A, Winyard PG, Jones AM. l-Citrulline supplementation improves O2 uptake kinetics and high-intensity exercise performance in humans. J Appl Physiol (1985). 2015 Aug 15;119(4):385-95. doi: 10.1152/japplphysiol.00192.2014. Epub 2015 May 28.
- Viribay A, Arribalzaga S, Mielgo-Ayuso J, Castaneda-Babarro A, Seco-Calvo J, Urdampilleta A. Effects of 120 g/h of Carbohydrates Intake during a Mountain Marathon on Exercise-Induced Muscle Damage in Elite Runners. Nutrients. 2020 May 11;12(5):1367. doi: 10.3390/nu12051367.
- Wang JM, Gu CH, Tao L, Wu XL. Effect of surgery and efferent duct ligation on testicular blood flow and testicular steroidogenesis in the rat. J Reprod Fertil. 1985 Jan;73(1):191-6. doi: 10.1530/jrf.0.0730191.
- Monau TR, Vargas VE, Zhang L, Myers DA, Ducsay CA. Nitric oxide inhibits ACTH-induced cortisol production in near-term, long-term hypoxic ovine fetal adrenocortical cells. Reprod Sci. 2010 Oct;17(10):955-62. doi: 10.1177/1933719110376092. Epub 2010 Aug 16.
- Milton-Laskibar I, Martinez JA, Portillo MP. Current Knowledge on Beetroot Bioactive Compounds: Role of Nitrate and Betalains in Health and Disease. Foods. 2021 Jun 7;10(6):1314. doi: 10.3390/foods10061314.
- Clifford T, Bell O, West DJ, Howatson G, Stevenson EJ. The effects of beetroot juice supplementation on indices of muscle damage following eccentric exercise. Eur J Appl Physiol. 2016 Feb;116(2):353-62. doi: 10.1007/s00421-015-3290-x. Epub 2015 Nov 4.
- Garnacho-Castano MV, Palau-Salva G, Serra-Paya N, Ruiz-Hermosel M, Berbell M, Vinals X, Bataller MG, Carbonell T, Vilches-Saez S, Cobo EP, Molina-Raya L. Understanding the effects of beetroot juice intake on CrossFit performance by assessing hormonal, metabolic and mechanical response: a randomized, double-blind, crossover design. J Int Soc Sports Nutr. 2020 Nov 13;17(1):56. doi: 10.1186/s12970-020-00388-z.
- da Silva DK, Jacinto JL, de Andrade WB, Roveratti MC, Estoche JM, Balvedi MCW, de Oliveira DB, da Silva RA, Aguiar AF. Citrulline Malate Does Not Improve Muscle Recovery after Resistance Exercise in Untrained Young Adult Men. Nutrients. 2017 Oct 18;9(10):1132. doi: 10.3390/nu9101132.
- Wax B, Kavazis AN, Luckett W. Effects of Supplemental Citrulline-Malate Ingestion on Blood Lactate, Cardiovascular Dynamics, and Resistance Exercise Performance in Trained Males. J Diet Suppl. 2016;13(3):269-82. doi: 10.3109/19390211.2015.1008615. Epub 2015 Feb 12.
- Perez-Guisado J, Jakeman PM. Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. J Strength Cond Res. 2010 May;24(5):1215-22. doi: 10.1519/JSC.0b013e3181cb28e0.
- McMahon NF, Leveritt MD, Pavey TG. The Effect of Dietary Nitrate Supplementation on Endurance Exercise Performance in Healthy Adults: A Systematic Review and Meta-Analysis. Sports Med. 2017 Apr;47(4):735-756. doi: 10.1007/s40279-016-0617-7.
- Jones AM, Thompson C, Wylie LJ, Vanhatalo A. Dietary Nitrate and Physical Performance. Annu Rev Nutr. 2018 Aug 21;38:303-328. doi: 10.1146/annurev-nutr-082117-051622.
- Richards JC, Racine ML, Hearon CM Jr, Kunkel M, Luckasen GJ, Larson DG, Allen JD, Dinenno FA. Acute ingestion of dietary nitrate increases muscle blood flow via local vasodilation during handgrip exercise in young adults. Physiol Rep. 2018 Jan;6(2):e13572. doi: 10.14814/phy2.13572.
- Curis E, Nicolis I, Moinard C, Osowska S, Zerrouk N, Bénazeth S, Cynober L. Almost all about citrulline in mammals. Amino Acids. 2005 Nov;29(3):177-205. Epub 2005 Aug 8. Review.
- Rammos C, Luedike P, Hendgen-Cotta U, Rassaf T. Potential of dietary nitrate in angiogenesis. World J Cardiol. 2015 Oct 26;7(10):652-7. doi: 10.4330/wjc.v7.i10.652.
- Wylie LJ, Park JW, Vanhatalo A, Kadach S, Black MI, Stoyanov Z, Schechter AN, Jones AM, Piknova B. Human skeletal muscle nitrate store: influence of dietary nitrate supplementation and exercise. J Physiol. 2019 Dec;597(23):5565-5576. doi: 10.1113/JP278076. Epub 2019 Jul 27.
- Daab W, Bouzid MA, Lajri M, Bouchiba M, Saafi MA, Rebai H. Chronic Beetroot Juice Supplementation Accelerates Recovery Kinetics following Simulated Match Play in Soccer Players. J Am Coll Nutr. 2021 Jan;40(1):61-69. doi: 10.1080/07315724.2020.1735571. Epub 2020 Mar 3.
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)
May 1, 2018
Primary Completion (Actual)
August 30, 2018
Study Completion (Actual)
October 1, 2021
Study Registration Dates
First Submitted
October 2, 2021
First Submitted That Met QC Criteria
November 21, 2021
First Posted (Actual)
December 3, 2021
Study Record Updates
Last Update Posted (Actual)
December 3, 2021
Last Update Submitted That Met QC Criteria
November 21, 2021
Last Verified
November 1, 2021
More Information
Terms related to this study
Other Study ID Numbers
- ULE-020-2020
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
product manufactured in and exported from the U.S.
Yes
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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