Long-Term Effect of Combined Citrulline and Nitrate-Rich Beetroot Extract Supplementation

NCT05143879 | Completed DMC

• 1 other identifier: ULE-020-2020
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Citrulline; Nitrate; Athletes

Keywords

triathlon; performance; ergogenic aids; muscle fatigue; recovery; hormones

Outcome Measures

Primary Outcomes (10)

• Cortisol

  μg/dL

  9 weeks

• Testosterone

  ng/mL

  9 weeks

• Testosterone to cortisol ratio

  ng/mL

  9 weeks

• Urea

  mg/dl

  9 weeks

• Creatinine

  mg/dl

  9 weeks

• AST

  U/L

  9 weeks

• ALT

  U/L

  9 weeks

• GGT

  U/L

  9 weeks

• LDH

  U/L

  9 weeks

• CK

  U/L

  9 weeks

Study Arms (4)

Placebo

PLACEBO COMPARATOR

8 subjects took 3 g/kg/day of placebo during 9 weeks

Dietary Supplement: Placebo

Nitrate

ACTIVE COMPARATOR

8 subjects took 3 g/kg/day of nitrate during 9 weeks

Dietary Supplement: Nitrate

Citrulline

ACTIVE COMPARATOR

8 subjects took 3 g/kg/day of citrulline during 9 weeks

Dietary Supplement: Citrulline

Nitrate plus Citrulline

ACTIVE COMPARATOR

8 subjects took 3 g/kg/day of nitrate plus citrulline during 9 weeks

Dietary Supplement: Nitrate plus Citrulline

Interventions

Citrulline DIETARY_SUPPLEMENT

3 g/day during 9 weeks

Citrulline

Nitrate DIETARY_SUPPLEMENT

300 mg/day during 9 weeks

Nitrate

Nitrate plus Citrulline DIETARY_SUPPLEMENT

3 g/day of citrulline and 300 mg/day of nitrate during 9 weeks

Nitrate plus Citrulline

Placebo DIETARY_SUPPLEMENT

3 g/day during 9 weeks

Also known as: Cellulose

Placebo

Eligibility Criteria

• Age: 25 Years - 35 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• weeks without taking other nutritional supplements

You may not qualify if:

• Men under 25 and over 35 years of age.
• Non triathletes
• Less than 5 years of experience
• With any disease
• Smokers
• Alcohol drinkers

Sponsors & Collaborators

• Burgos Nutrition: lead
• Universidad de León: collaborator
• University of the Basque Country (UPV/EHU): collaborator
• University of Valladolid: collaborator

Study Sites (1)

University of Leon

León, Castille and León, 24004, Spain

Location

Related Publications (20)

• 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.

  PMID: 31977835 RESULT

• 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.

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• 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.

  PMID: 10793157 RESULT

• 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.

  PMID: 26023227 RESULT

• 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.

  PMID: 32403259 RESULT

• 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.

  PMID: 3968652 RESULT

• 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.

  PMID: 20713972 RESULT

• 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.

  PMID: 34200431 RESULT

• 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.

  PMID: 26537365 RESULT

• 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.

  PMID: 33187518 RESULT

• 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.

  PMID: 29057836 RESULT

• 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.

  PMID: 25674699 RESULT

• 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.

  PMID: 20386132 RESULT

• 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.

  PMID: 27600147 RESULT

• 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.

  PMID: 30130468 RESULT

• 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.

  PMID: 29380952 RESULT

• Curis E, Nicolis I, Moinard C, Osowska S, Zerrouk N, Benazeth S, Cynober L. Almost all about citrulline in mammals. Amino Acids. 2005 Nov;29(3):177-205. doi: 10.1007/s00726-005-0235-4. Epub 2005 Aug 8.

  PMID: 16082501 RESULT

• 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.

  PMID: 26516419 RESULT

• 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.

  PMID: 31350908 RESULT

• 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.

  PMID: 32125249 RESULT

MeSH Terms

Interventions

Citrulline; Nitrates; Cellulose

Intervention Hierarchy (Ancestors)

Amino Acids, Diamino; Amino Acids; Amino Acids, Peptides, and Proteins; Anions; Ions; Electrolytes; Inorganic Chemicals; Nitric Acid; Nitrogen Compounds; Organic Chemicals; Glucans; Biopolymers; Polymers; Macromolecular Substances; Polysaccharides; Carbohydrates; Biomedical and Dental Materials; Manufactured Materials; Technology, Industry, and Agriculture

Study Officials

• Jose Burgos Balmaseda, Graduate

  University of Leon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: This study was a double-blind, placebo-controlled trial where participants (n = 32) were random-ized 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)
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Model Details: 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 CM 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 (T), cortisol (C), and T/C) in male trained triathletes.

Study Record Dates

• First Submitted: October 2, 2021
• First Posted: December 3, 2021
• Study Start: May 1, 2018
• Primary Completion: August 30, 2018
• Study Completion: October 1, 2021
• Last Updated: December 3, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)