Supplementation with Nitric Oxide Precursors for Strength Performance: A Review of the Current Literature

Overview

Journal Nutrients

Date 2023 Feb 11

PMID 36771366

Authors

Adam M Gonzalez

Jeremy R Townsend

Anthony G Pinzone

Jay R Hoffman

Affiliations

Soon will be listed here.

Abstract

Nitric-oxide-stimulating dietary supplements are widely available and marketed to strength athletes and weightlifters seeking to increase muscle performance and augment training adaptations. These supplements contain ingredients classified as nitric oxide (NO) precursors (i.e., "NO boosters"). Endogenous NO is generated via a nitric oxide synthase (NOS)-dependent pathway and a NOS-independent pathway that rely on precursors including L-arginine and nitrates, with L-citrulline serving as an effective precursor of L-arginine. Nitric oxide plays a critical role in endothelial function, promoting relaxation of vascular smooth muscle and subsequent dilation which may favorably impact blood flow and augment mechanisms contributing to skeletal muscle performance, hypertrophy, and strength adaptations. The aim of this review is to describe the NO production pathways and summarize the current literature on the effects of supplementation with NO precursors for strength and power performance. The information will allow for an informed decision when considering the use of L-arginine, L-citrulline, and nitrates to improve muscular function by increasing NO bioavailability.

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References

Ferguson S, Hirai D, Copp S, Holdsworth C, Allen J, Jones A . Impact of dietary nitrate supplementation via beetroot juice on exercising muscle vascular control in rats. J Physiol. 2012; 591(2):547-57. PMC: 3577528. DOI: 10.1113/jphysiol.2012.243121. View

Le Roux-Mallouf T, Laurent J, Besset D, Marillier M, Larribaut J, Belaidi E . Effects of acute nitric oxide precursor intake on peripheral and central fatigue during knee extensions in healthy men. Exp Physiol. 2019; 104(7):1100-1114. DOI: 10.1113/EP087493. View

Modin A, Bjorne H, Herulf M, Alving K, Weitzberg E, Lundberg J . Nitrite-derived nitric oxide: a possible mediator of 'acidic-metabolic' vasodilation. Acta Physiol Scand. 2001; 171(1):9-16. DOI: 10.1046/j.1365-201X.2001.00771.x. View

Allerton T, Proctor D, Stephens J, Dugas T, Spielmann G, Irving B . l-Citrulline Supplementation: Impact on Cardiometabolic Health. Nutrients. 2018; 10(7). PMC: 6073798. DOI: 10.3390/nu10070921. View

Gonzalez A, Pinzone A, Lipes S, Mangine G, Townsend J, Allerton T . Effect of watermelon supplementation on exercise performance, muscle oxygenation, and vessel diameter in resistance-trained men. Eur J Appl Physiol. 2022; 122(7):1627-1638. DOI: 10.1007/s00421-022-04940-4. View

Khalaf D, Kruger M, Wehland M, Infanger M, Grimm D . The Effects of Oral l-Arginine and l-Citrulline Supplementation on Blood Pressure. Nutrients. 2019; 11(7). PMC: 6683098. DOI: 10.3390/nu11071679. View

Le Roux-Mallouf T, Vibert F, Doutreleau S, Verges S . Effect of acute nitrate and citrulline supplementation on muscle microvascular response to ischemia-reperfusion in healthy humans. Appl Physiol Nutr Metab. 2017; 42(9):901-908. DOI: 10.1139/apnm-2017-0081. View

Kramer S, Baur D, Spicer M, Vukovich M, Ormsbee M . The effect of six days of dietary nitrate supplementation on performance in trained CrossFit athletes. J Int Soc Sports Nutr. 2016; 13:39. PMC: 5093951. DOI: 10.1186/s12970-016-0150-y. View

Garnacho-Castano M, Sanchez-Nuno S, Molina-Raya L, Carbonell T, Mate-Munoz J, Pleguezuelos-Cobo E . Circulating nitrate-nitrite reduces oxygen uptake for improving resistance exercise performance after rest time in well-trained CrossFit athletes. Sci Rep. 2022; 12(1):9671. PMC: 9188609. DOI: 10.1038/s41598-022-13786-x. View

10.

Mosher S, Sparks S, Williams E, Bentley D, Mc Naughton L . Ingestion of a Nitric Oxide Enhancing Supplement Improves Resistance Exercise Performance. J Strength Cond Res. 2016; 30(12):3520-3524. DOI: 10.1519/JSC.0000000000001437. View

11.

Townsend J, Hart T, Haynes 4th J, Woods C, Toy A, Pihera B . Influence of Dietary Nitrate Supplementation on Physical Performance and Body Composition Following Offseason Training in Division I Athletes. J Diet Suppl. 2021; 19(4):534-549. DOI: 10.1080/19390211.2021.1900482. View

12.

Lundberg J, Weitzberg E, Gladwin M . The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov. 2008; 7(2):156-67. DOI: 10.1038/nrd2466. View

13.

Smith L, Smith J, Criswell D . Involvement of nitric oxide synthase in skeletal muscle adaptation to chronic overload. J Appl Physiol (1985). 2002; 92(5):2005-11. DOI: 10.1152/japplphysiol.00950.2001. View

14.

Wax B, Kavazis A, Luckett W . Effects of Supplemental Citrulline-Malate Ingestion on Blood Lactate, Cardiovascular Dynamics, and Resistance Exercise Performance in Trained Males. J Diet Suppl. 2015; 13(3):269-82. DOI: 10.3109/19390211.2015.1008615. View

15.

Vanhatalo A, Bailey S, Blackwell J, DiMenna F, Pavey T, Wilkerson D . Acute and chronic effects of dietary nitrate supplementation on blood pressure and the physiological responses to moderate-intensity and incremental exercise. Am J Physiol Regul Integr Comp Physiol. 2010; 299(4):R1121-31. DOI: 10.1152/ajpregu.00206.2010. View

16.

Hwang P, Morales Marroquin F, Gann J, Andre T, McKinley-Barnard S, Kim C . Eight weeks of resistance training in conjunction with glutathione and L-Citrulline supplementation increases lean mass and has no adverse effects on blood clinical safety markers in resistance-trained males. J Int Soc Sports Nutr. 2018; 15(1):30. PMC: 6020314. DOI: 10.1186/s12970-018-0235-x. View

17.

C Silva K, Costa B, Gomes A, Saunders B, Mota J . Factors that Moderate the Effect of Nitrate Ingestion on Exercise Performance in Adults: A Systematic Review with Meta-Analyses and Meta-Regressions. Adv Nutr. 2022; 13(5):1866-1881. PMC: 9526841. DOI: 10.1093/advances/nmac054. View

18.

Jones A, Thompson C, Wylie L, Vanhatalo A . Dietary Nitrate and Physical Performance. Annu Rev Nutr. 2018; 38:303-328. DOI: 10.1146/annurev-nutr-082117-051622. View

19.

Bahadoran Z, Mirmiran P, Kashfi K, Ghasemi A . Endogenous flux of nitric oxide: Citrulline is preferred to Arginine. Acta Physiol (Oxf). 2020; 231(3):e13572. DOI: 10.1111/apha.13572. View

20.

Larsen F, Weitzberg E, Lundberg J, Ekblom B . Effects of dietary nitrate on oxygen cost during exercise. Acta Physiol (Oxf). 2007; 191(1):59-66. DOI: 10.1111/j.1748-1716.2007.01713.x. View