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Acute Effects of Citrulline Supplementation on High-Intensity Strength and Power Performance: A Systematic Review and Meta-Analysis

Abstract

Background

Citrulline is an increasingly common dietary supplement that is thought to enhance exercise performance by increasing nitric oxide production. In the last 5 years, several studies have investigated the effects of citrulline supplements on strength and power outcomes, with mixed results reported. To date, the current authors are unaware of any attempts to systematically review this emerging body of literature.

Objective

The current study sought to conduct a systematic review and meta-analysis of the literature describing the effects of citrulline supplementation on strength and power outcomes.

Methods

A comprehensive, systematic search of three prominent research databases was performed to find peer-reviewed, English language, original research studies evaluating the effects of citrulline supplementation on indices of high-intensity exercise performance in healthy men and women. Outcomes included strength and power variables from performance tests involving multiple repetitive muscle actions of large muscle groups, consisting of either resistance training sets or sprints lasting 30 s or less. Tests involving isolated actions of small muscle groups or isolated attempts of single-jump tasks were not included for analysis due to differences in metabolic requirements. Studies were excluded from consideration if they lacked a placebo condition for comparison, were carried out in clinical populations, provided a citrulline dose of less than 3 g, provided the citrulline dose less than 30 min prior to exercise testing, or combined the citrulline ingredient with creatine, caffeine, nitrate, or other ergogenic ingredients.

Results

Twelve studies, consisting of 13 total independent samples (n = 198 participants), met the inclusion criteria. Between-study variance, heterogeneity, and inconsistency across studies were low (Cochrane’s Q = 6.9, p = 0.86; τ2 = 0.0 [0.0, 0.08], I2 = 0.0 [0.0, 40.0]), and no funnel plot asymmetry was present. Results of the meta-analysis identified a significant benefit for citrulline compared to placebo treatments (p = 0.036), with a small pooled standardized mean difference (SMD; Hedges’ G) of 0.20 (95% confidence interval 0.01–0.39).

Conclusion

The effect size was small (0.20), and confidence intervals for each individual study crossed the line of null effect. However, the results may be relevant to high-level athletes, in which competitive outcomes are decided by small margins. Further research is encouraged to fully elucidate the effects of potential moderating study characteristics, such as the form of citrulline supplement, citrulline dose, sex, age, and strength versus power tasks.

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References

  1. 1.

    Joyner MJ, Casey DP. Regulation of increased blood flow (hyperemia) to muscles during exercise: a hierarchy of competing physiological needs. Physiol Rev. 2015;95(2):549–601.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Bailey SJ, Vanhatalo A, Winyard PG, Jones AM. The nitrate-nitrite-nitric oxide pathway: its role in human exercise physiology. Eur J Sport Sci. 2011;12(4):309–20.

    Article  Google Scholar 

  3. 3.

    Chappell AJ, Allwood DM, Johns R, Brown S, Sultana K, Anand A, et al. Citrulline malate supplementation does not improve German Volume Training performance or reduce muscle soreness in moderately trained males and females. J Int Soc Sports Nutr. 2018;15(1):42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Cunniffe B, Papageorgiou M, O’Brien B, Davies NA, Grimble GK, Cardinale M. Acute citrulline-malate supplementation and high-intensity cycling performance. J Strength Cond Res. 2016;30(9):2638–47.

    Article  PubMed  Google Scholar 

  5. 5.

    Cutrufello PT, Gadomski SJ, Zavorsky GS. The effect of l-citrulline and watermelon juice supplementation on anaerobic and aerobic exercise performance. J Sports Sci. 2015;33(14):1459–66.

    Article  PubMed  Google Scholar 

  6. 6.

    Farney TM, Bliss MV, Hearon CM, Salazar DA. The effect of citrulline malate supplementation on muscle fatigue among healthy participants. J Strength Cond Res. 2017. https://doi.org/10.1519/jsc.0000000000002356 (ePub ahead of print).

    Article  Google Scholar 

  7. 7.

    Gonzalez AM, Spitz RW, Ghigiarelli JJ, Sell KM, Mangine GT. Acute effect of citrulline malate supplementation on upper-body resistance exercise performance in recreationally resistance-trained men. J Strength Cond Res. 2017. https://doi.org/10.1519/jsc.0000000000002373 (ePub ahead of print).

    Article  PubMed  Google Scholar 

  8. 8.

    Glenn JM, Gray M, Jensen A, Stone MS, Vincenzo JL. Acute citrulline-malate supplementation improves maximal strength and anaerobic power in female, masters athletes tennis players. Eur J Sport Sci. 2016;16(8):1095–103.

    Article  PubMed  Google Scholar 

  9. 9.

    Glenn JM, Gray M, Wethington LN, Stone MS, Stewart RW Jr, Moyen NE. Acute citrulline malate supplementation improves upper- and lower-body submaximal weightlifting exercise performance in resistance-trained females. Eur J Nutr. 2017;56(2):775–84.

    Article  CAS  PubMed  Google Scholar 

  10. 10.

    Perez-Guisado J, Jakeman PM. Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. J Strength Cond Res. 2010;24(5):1215–22.

    Article  PubMed  Google Scholar 

  11. 11.

    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.

    Article  CAS  PubMed  Google Scholar 

  12. 12.

    Wax B, Kavazis AN, Weldon K, Sperlak J. Effects of supplemental citrulline malate ingestion during repeated bouts of lower-body exercise in advanced weightlifters. J Strength Cond Res. 2015;29(3):786–92.

    Article  PubMed  Google Scholar 

  13. 13.

    Dickinson A, Blatman J, El-Dash N, Franco JC. Consumer usage and reasons for using dietary supplements: report of a series of surveys. J Am Coll Nutr. 2014;33(2):176–82.

    Article  CAS  PubMed  Google Scholar 

  14. 14.

    Bloomer RJ. Nitric oxide supplements for sports. Strength Cond J. 2010;32(2):14–20.

    Article  Google Scholar 

  15. 15.

    Bloomer RJ, Farney TM, Trepanowski JF, McCarthy CG, Canale RE, Schilling BK. Comparison of pre-workout nitric oxide stimulating dietary supplements on skeletal muscle oxygen saturation, blood nitrate/nitrite, lipid peroxidation, and upper body exercise performance in resistance trained men. J Int Soc Sports Nutr. 2010;7:16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Bescos R, Sureda A, Tur JA, Pons A. The effect of nitric-oxide-related supplements on human performance. Sports Med. 2012;42(2):99–117.

    Article  PubMed  Google Scholar 

  17. 17.

    Liu TH, Wu CL, Chiang CW, Lo YW, Tseng HF, Chang CK. No effect of short-term arginine supplementation on nitric oxide production, metabolism and performance in intermittent exercise in athletes. J Nutr Biochem. 2009;20(6):462–8.

    Article  CAS  PubMed  Google Scholar 

  18. 18.

    Sunderland KL, Greer F, Morales J. VO2max and ventilatory threshold of trained cyclists are not affected by 28-day l-arginine supplementation. J Strength Cond Res. 2011;25(3):833–7.

    Article  PubMed  Google Scholar 

  19. 19.

    Bescos R, Gonzalez-Haro C, Pujol P, Drobnic F, Alonso E, Santolaria ML, et al. Effects of dietary l-arginine intake on cardiorespiratory and metabolic adaptation in athletes. Int J Sport Nutr Exerc Metab. 2009;19(4):355–65.

    Article  CAS  PubMed  Google Scholar 

  20. 20.

    Tsai PH, Tang TK, Juang CL, Chen KW, Chi CA, Hsu MC. Effects of arginine supplementation on post-exercise metabolic responses. Chin J Physiol. 2009;52(3):136–42.

    Article  CAS  PubMed  Google Scholar 

  21. 21.

    Schwedhelm E, Maas R, Freese R, Jung D, Lukacs Z, Jambrecina A, et al. Pharmacokinetic and pharmacodynamic properties of oral l-citrulline and l-arginine: impact on nitric oxide metabolism. Br J Clin Pharmacol. 2008;65(1):51–9.

    Article  CAS  PubMed  Google Scholar 

  22. 22.

    Bendahan D, Mattei JP, Ghattas B, Confort-Gouny S, Le Guern ME, Cozzone PJ. Citrulline/malate promotes aerobic energy production in human exercising muscle. Br J Sports Med. 2002;36(4):282–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Sureda A, Cordova A, Ferrer MD, Perez G, Tur JA, Pons A. l-citrulline-malate influence over branched chain amino acid utilization during exercise. Eur J Appl Physiol. 2010;110(2):341–51.

    Article  CAS  PubMed  Google Scholar 

  24. 24.

    Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097.

    Article  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Borenstein M, Hedges LV, Higgins JPT, Rothstein HR. Introduction to meta-analysis. Chichester: Wiley; 2009.

    Book  Google Scholar 

  26. 26.

    Borenstein M, Hedges LV, Higgins JP, Rothstein HR. A basic introduction to fixed-effect and random-effects models for meta-analysis. Res Synth Methods. 2010;1(2):97–111.

    Article  PubMed  Google Scholar 

  27. 27.

    Cohen J. A power primer. Psychol Bull. 1992;112(1):155–9.

    Article  CAS  PubMed  Google Scholar 

  28. 28.

    Borenstein M. Effect sizes for continuous data. In: Cooper H, Hedges LV, Valentine JC, editors. The handbook of research synthesis and meta analysis. 2nd ed. New York: Russell Sage Foundation; 2009. p. 279–93.

    Google Scholar 

  29. 29.

    Baker D, Nance S. The relation between strength and power in professional rugby league players. J Strength Cond Res. 1999;13(3):224–9.

    Google Scholar 

  30. 30.

    Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.

    Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–60.

    Article  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Duval S, Tweedie R. Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics. 2000;56(2):455–63.

    Article  CAS  PubMed  Google Scholar 

  34. 34.

    Branch JD. Effect of creatine supplementation on body composition and performance: a meta-analysis. Int J Sport Nutr Exerc Metab. 2003;13(2):198–226.

    Article  CAS  PubMed  Google Scholar 

  35. 35.

    Grgic J, Trexler ET, Lazinica B, Pedisic Z. Effects of caffeine intake on muscle strength and power: a systematic review and meta-analysis. J Int Soc Sports Nutr. 2018;15:11.

    Article  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Christensen PM, Shirai Y, Ritz C, Nordsborg NB. Caffeine and bicarbonate for speed. A meta-analysis of legal supplements potential for improving intense endurance exercise performance. Front Physiol. 2017;8:240.

    Article  PubMed  PubMed Central  Google Scholar 

  37. 37.

    DeWeese BH, Hornsby G, Stone M, Stone MH. The training process: Planning for strength–power training in track and field. Part 1: theoretical aspects. J Sport Health Sci. 2015;4(4):308–17.

    Article  Google Scholar 

  38. 38.

    Rodgers AL, Webber D, de Charmoy R, Jackson GE, Ravenscroft N. Malic acid supplementation increases urinary citrate excretion and urinary pH: implications for the potential treatment of calcium oxalate stone disease. J Endourol. 2014;28(2):229–36.

    Article  PubMed  Google Scholar 

  39. 39.

    Martinez-Sanchez A, Alacid F, Rubio-Arias JA, Fernandez-Lobato B, Ramos-Campo DJ, Aguayo E. Consumption of watermelon juice enriched in l-citrulline and pomegranate ellagitannins enhanced metabolism during physical exercise. J Agric Food Chem. 2017;65(22):4395–404.

    Article  CAS  PubMed  Google Scholar 

  40. 40.

    Wu JL, Wu QP, Huang JM, Chen R, Cai M, Tan JB. Effects of l-malate on physical stamina and activities of enzymes related to the malate-aspartate shuttle in liver of mice. Physiol Res. 2007;56(2):213–20.

    CAS  PubMed  Google Scholar 

  41. 41.

    Brown AC, Macrae HS, Turner NS. Tricarboxylic-acid-cycle intermediates and cycle endurance capacity. Int J Sport Nutr Exerc Metab. 2004;14(6):720–9.

    Article  CAS  PubMed  Google Scholar 

  42. 42.

    da Silva DK, Jacinto JL, de Andrade WB, Roveratti MC, Estoche JM, Balvedi MCW, et al. Citrulline malate does not improve muscle recovery after resistance exercise in untrained young adult men. Nutrients. 2017;9(10):E1132.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors would like to thank Dr. Charles Poole for his constructive feedback on the manuscript.

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Correspondence to Abbie E. Smith-Ryan.

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Ethical Standards

The current project was conducted and reported in accordance with PRISMA guidelines.

Funding

No funding was obtained to support the current manuscript.

Conflict of Interest

Eric T. Trexler, Adam M. Persky, Eric D. Ryan, Todd A. Schwartz, Lee Stoner, and Abbie E. Smith-Ryan declare no conflicts of interest.

Data Availability Statement

Data for the current analysis are available upon request, and can be obtained by contacting the corresponding author.

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Trexler, E.T., Persky, A.M., Ryan, E.D. et al. Acute Effects of Citrulline Supplementation on High-Intensity Strength and Power Performance: A Systematic Review and Meta-Analysis. Sports Med 49, 707–718 (2019). https://doi.org/10.1007/s40279-019-01091-z

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