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Effects of Amino Acids L-Arginine on Physical Performance
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Consumption of amino acids L-arginine (L-Arg) and L-citrulline (L-Cit) are purported to increase nitric oxide (NO) production and improve physical performance. However, standalone L-Arg supplementation seems ineffective in increasing NO synthesis or improve physical performance and perceptual feelings of exertion among recreationally active and trained athletes.

exercise performance nitric oxide L-arginine
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    1. Effects of L-Arginine on Nitric Oxide Production

    Supplementation to increase L-Arg has drawn significant attention for its role in improving exercise performance through increasing NO synthesis [1]. Trained male cyclists ingested 0.075 g/kg L-Arg or a placebo 60 min before completing the submaximal cycling exercise protocol. Plasma metabolites were recorded in different time points including: 0 min (pre-supplementation), 60 min (start of exercise), 120 min (end of exercise/start of rest), and 180 min (end of rest period) [2]. Plasma L-Arg concentration increased from a resting concentration of 273 µM/L to about 679 µM/L at 60 min post-supplementation, and after that progressively decreased to eventually 377 µM/L at 180 min compared to 327 µM/L at 60 min and 265 µM/L at 180 min for the placebo. However, plasma L-Arg concentration was significantly increased for the supplement group compared to the placebo in all eight-time points from 60 min post-supplementation (p < 0.05). There were no significant differences in plasma nitrate/nitrite concentration in the supplement group compared to the placebo (p > 0.05). At time point 0, plasma nitrate/nitrite concentration was about 11.5 µM/L for the supplementation group and 15.1 µM/L for placebo; at time point 180, plasma nitrate/nitrite concentration was approximately 14.5 µM/L for supplementation group and 13.7 µM/L for placebo. Similarly, ingestion of 6 g/day L-Arg for three days significantly increased plasma L-Arg concentration from 60.1 ± 3.0 µM/L at baseline to 78.9 ± 6.5 µM/L 60 min post-supplementation (p < 0.001). Yet, there was no significant difference in plasma nitrate/nitrite concentrations for the supplement group (235.41 µM/L) compared to the placebo group (260.40 µM/L; p > 0.05) 60 min post-supplementation among elite judo male athletes [3]. In a study with 6 g L-Arg acute supplementation, Meirelles and Matsuura (2016) reported no significant changes in plasma nitrate concentration from pre-supplementation values to 60 min post-supplementation and exercise; the supplement group’s plasma nitrate concentration slightly increased from 10.95 ± 4.09 to 11.99 ± 2.5 mM compared to the placebo group, which slightly decreased from 13.01 ± 1.18 to 11.83 ± 2.81 mM (p > 0.05) among resistance trained physical education students [4].
    Vanhatalo et al. (2013) reported no significant changes in plasma nitrite concentrations from the supplement group compared to the placebo at the same time points, 0 to 90 min [5]. Plasma nitrite concentration of the supplement group changed from 204 ± 79 to 241 ± 114 nM (p > 0.05) compared to the placebo group, which changed from 223 ± 107 to 222 ± 105 nM (p > 0.05). Similarly, ingestion of 6 g L-Arg had no significant differences in plasma NO markers at all-time points for the supplementation group compared to the placebo in healthy male participants (0 min: 17.6 ± 3.9 vs. 14.6 ± 2.3 µM/L; 60 min: 16.8 ± 4.9 vs. 13.7 ± 2.7; 120 min: 15.1 ± 2.8 vs. 13.5 ± 3.5 µM/L; all at p > 0.05) [6]. Blum et al. (2000) reported no significant changes in plasma NO synthesis following daily oral administration of 6 g L-Arg or the placebo for one month in healthy adult women (L-Arg: 42.1 ± 24.5 vs. Pla: 39.1 ± 61.1 µM/L; p > 0.05) [7]. Based on these studies, a dose of 6 g L-Arg was ineffective in increasing NO. Viribay et al. (2020) suggested that a higher dose might be more efficacious [1]. However, Tang et al. (2011) reported that even 10 g L-Arg supplementation did not significantly change plasma nitrate and nitrite concentration among recreationally active male participants [8]. In support of this, Forbes and Bell (2011) reported that low and high acute doses of L-Arg supplementation had similar effects on plasma L-Arg levels, with neither significantly increasing blood markers of NO synthesis among active young males [9]. Alvares et al. (2012) reported that acute ingestion of L-Arg is insufficient to change systemic NO synthesis [6].
    Chronic supplementation with 6 g/day for four weeks among trained runners was not sufficient to significantly increase NO synthesis for the supplement group compared to the placebo group (week 0: 1.9 ± 0.4; week 4: 2.6 ± 0.8 µM/L vs. week 0: 1.8 ± 0.5; week 4: 2.2 ± 0.6 µM/L; p > 0.05) [10].
    Increasing and maintaining NO synthesis plays a major role in vasodilatory capacity and increases oxygen uptake in skeletal muscle [11]. The possible reason for the limited impact of L-Arg supplementation on NO synthesis may be related to L-Arg metabolism. The level of circulating plasma L-Arg is fundamental to increasing NO synthesis, and depleted plasma L-Arg may fail to upkeep NO synthesis. Augmenting NO production via oral consumption of L-Arg may be compromised. An estimated 60% of L-Arg is metabolized in the gastrointestinal tract, while a further estimated 15% is metabolized by the liver [12]. Alvares et al. (2012) suggested that there should be no need to supplement with L-Arg in healthy participants since sheer vascular stress is considered the main stimulus of endothelial NO synthesis during exercise [6]. Instead, L-Arg supplementation may benefit participants with atherosclerosis risk factors where endothelial dysfunction may impact NO synthesis [6]. Similarly, Chin-Dusting et al. (1996) reported that supplementation with L-Arg may not consistently improve endothelial function and muscle blood flow during exercise among patients [13]. Instead, favorable outcomes such as improvement in cardiac performance were reported in patients with moderate congestive heart failure [14].

    2. The Effects of L-Arginine on Physical Performance and Perceptual Responses to Exercise

    A limited beneficial effect was reported for wrestling elite athletes after ingesting a single dose of 1.5 g/10 kg body weight L-Arg capsule or placebo [15]. Time to exhaustion during an incremental test on a cycle ergometer was longer for the supplement group (1386.8 ± 69.5 s) compared to the placebo (1313 ± 90.8 s) (p < 0.05). There were no significant differences between the supplement and the placebo group for oxygen consumption (L-Arg: 52.47 ± 4.01 mL/kg/min vs. Pla: 52.07 ± 5.21 mL/kg/min), and heart rate (L-Arg: 181.09 ± 13.57 bpm vs. Pla: 185.89 ± 7.38 bpm) (p > 0.05). Pahlavani et al. (2017)reported that the ingestion of 2 g/kg body weight of L-Arg for 45 days significantly improved maximal oxygen consumption by 4.12 ± 6.07 mL/kg/min compared to the placebo (1.23 ± 3.36 mL/kg/min; p < 0.05) among male soccer players [16]. Interestingly, studies that reported significant improvements did not measure plasma concentrations of L-Arg, nitrate, or nitrite. Therefore, the mechanism that led to improvement in physical performance remains questionable in these studies.
    Contrary to the reported effect of L-Arg supplementation in improving favorable aerobic capacity outcomes among healthy participants when combined with other components such as aspartate, BCAA, or other amino acids [17][18][19], ingestion of 0.075 g/kg L-Arg 60 min before submaximal cycling exercise had no significant improvement in cardio-respiratory parameters measured at the start and finish of the 60 min cycling protocol among aerobically trained cyclists compared to the placebo [2]. The volume of oxygen consumption had no significant changes in the supplement (start: 35.2 ± 6.5, end: 37.0 ± 6.1 mL/kg/min) or placebo groups, respectively (start: 34.9 ± 6.2, end: 36.5 ± 5.9 mL/kg/min); a non-significant result was also observed regarding heart rate in the supplementation group (start: 137 ± 12, end: 145 ± 14 bpm) and the placebo group (start: 137 ± 13, end: 144 ± 17 bpm) (p > 0.05). There were no significant differences between L-Arg and placebo conditions in the diastolic pressure at the start (79 ± 5 vs. 79 ± 8 mmHg) or finish (72 ± 11 vs. 72 ± 10 mmHg), and for systolic pressure at the start (125 ± 7 vs. 125 ± 7.5 mmHg) or finish (161 ± 13 vs. 159 ± 16 mmHg) (all at p > 0.05) of the cycling protocol. Another study reported no significant changes in steady-state pulmonary oxygen uptake during moderate-intensity exercise after 6 g L-Arg beverage consumption for the supplement group compared to the placebo group (2.422 ± 333 vs. 2.407 ± 318 m/kg/min; p > 0.05), and also no significant changes in the time to tolerate severe exercise (552 ± 150 vs. 551 ± 140 s; p > 0.05) [5]. Moreover, chronic L-Arg intake did not improve performance in trained endurance athletes [20]. Similarly, consumption of 5 g L-Arg or 5.5 g dextrin twice a day for a total of 13 days yielded no significant differences in mean power output, with a mean difference of 0.5 W during cycling performance (p > 0.05) [21].
    Standalone L-Arg supplementation seems ineffective in improving strength among well-trained athletes or recreationally healthy participants [22]. For instance, growth hormone responses over time were blunted for the supplement group (288.4 ± 368.7 min/ng/mL) compared to a placebo (487.9 ± 487.0 min/ng/mL; p < 0.05), and there was no difference in RPE between the groups (14 ± 2 vs. 15 ± 2; p > 0.05) in resistance-trained athletes who consumed 0.075 g/kg of L-Arg or placebo 60 min prior to performing resistance exercise protocol [23]. Meirelles and Matsuura (2016) did not find significant differences in bench press and isokinetic knee extension performance after administration of 6 g L-Arg or placebo among resistance-trained physical education students [4]. Another study reported a substantial decline in post-exercise elbow extension (p = 0.014) and flexion peak torque (p < 0.001) after ingestion of 3 g L-Arg among physically active male and female participants [24]. The ineffectiveness of L-Arg may be related to its ability to blunt growth hormone response following exercise [25]. Resistance exercise alone is a potent stimulator of growth hormone release [26]. While L-Arg has been shown to increase growth hormone-releasing hormone, it does suppress endogenous growth hormone-inhibiting hormone and increases insulin-like growth factor 1 [27][28]. However, oral administration of L-Arg does not augment exercise-induced growth hormone increase [29]. Furthermore, growth hormone response to specific amino acid consumption is reportedly reduced in well-trained athletes [30]. A study by Alvares et al. (2014) suggested that only chronic L-Arg supplementation could stimulate growth hormone production in physically active participants [10]. Consistent with this suggestion, chronic L-Arg supplementation of about 1.5 to 2 g/day improved aerobic and anaerobic performance [1]. A study by Campell et al. (2006) reported that a chronic supplementation protocol might be effective for enhancing maximum bench press in strength-trained male participants [31]. However, a number of studies that reported the effectiveness of chronic L-Arg consumption had other active ingredients in the supplement, such as aspartate, ornithine, and alpha-ketoglutarate [18][20][28][32]. A study Hurst and Sinclair (2014) claimed that all the current literature that reported significant improvement with L-Arg supplementation had combined it with other compounds [33]. Furthermore, other authors reported no benefit of acute or chronic supplementation protocol of L-Arg 6 g/day for muscle strength, endurance, or the maximum number of repetitions [34].

    References

    1. Viribay, A.; Burgos, J.; Fernández-Landa, J.; Seco-Calvo, J.; Mielgo-Ayuso, J. Effects of arginine supplementation on athletic performance based on energy metabolism: A systematic review and meta-analysis. Nutrients 2020, 12, 1300.
    2. Forbes, S.C.; Harber, V.; Bell, G.J. The acute effects of l-arginine on hormonal and metabolic responses during submaximal exercise in trained cyclists. Int. J. Sport Nutr. Exerc. Metab. 2013, 23, 369–377.
    3. Liu, T.H.; Wu, C.L.; Chiang, C.W.; Lo, Y.W.; Tseng, H.F.; Chang, C.K. No effect of short-term arginine supplementation on nitric oxide production, metabolism and performance in intermittent exercise in athletes. J. Nutr. Biochem. 2009, 20, 462–468.
    4. Meirelles, C.M.; Matsuura, C. Acute supplementation of l-arginine affects neither strength performance nor nitric oxide production. J. Sports Med. Phys. Fit. 2016, 58, 216–220.
    5. Vanhatalo, A.; Bailey, S.; DiMenna, F.; Blackwell, J.; Wallis, G.; Jones, A. No effect of acute l-arginine supplementation on O2 cost or exercise tolerance. Eur. J. Appl. Physiol. 2013, 113, 1805–1819.
    6. Alvares, T.S.; Conte-Junior, C.A.; Silva, J.T.; Paschoalin, V.M. Acute l-arginine supplementation does not increase nitric oxide production in healthy subjects. Nutr. Metab. 2012, 9, 1–8.
    7. Blum, A.; Hathaway, L.; Mincemoyer, R.; Schenke, W.H.; Kirby, M.; Csako, G.; Waclawiw, M.A.; Panza, J.A.; Cannon, R.O. Effects of oral l-arginine on endothelium-dependent vasodilation and markers of inflammation in healthy postmenopausal women. J. Am. Coll. Cardiol. 2000, 35, 271–276.
    8. Tang, J.E.; Lysecki, P.J.; Manolakos, J.J.; MacDonald, M.J.; Tarnopolsky, M.A.; Phillips, S.M. Bolus arginine supplementation affects neither muscle blood flow nor muscle protein synthesis in young men at rest or after resistance exercise. J. Nutr. 2011, 141, 195–200.
    9. Forbes, S.C.; Bell, G.J. The acute effects of a low and high dose of oral L-arginine supplementation in young active males at rest. Appl. Physiol. Nutr. Metab. 2011, 36, 405–411.
    10. Alvares, T.S.; Conte-Junior, C.A.; Silva, J.T.; Paschoalin, V.M. L-arginine does not improve biochemical and hormonal response in trained runners after 4 weeks of supplementation. Nutr. Res. 2014, 34, 31–39.
    11. Maiorana, A.; O’Driscoll, G.; Taylor, R.; Green, D. Exercise and the nitric oxide vasodilator system. Sports Med. 2003, 33, 1013–1035.
    12. O’Sullivan, D.; Brosnan, J.T.; Brosnan, M.E. Catabolism of arginine and ornithine in the perfused rat liver: Effect of dietary protein and of glucagon. Am. J. Physiol. Endocrinol. Metab. 2000, 278, 516–521.
    13. Chin-Dusting, J.P.; Alexander, C.T.; Arnold, P.J.; Hodgson, W.C.; Lux, A.S.; Jennings, G.L. Effects of in vivo and in vitro l-arginine supplementation on healthy human vessels. J. Cardiovasc. Pharmacol. 1996, 28, 158–166.
    14. Koifman, B.; Wollman, Y.; Bogomolny, N.; Chernichowsky, T.; Finkelstein, A.; Peer, G.; Scherez, J.; Bium, M.; Laniado, S.; Laina, A.; et al. Improvement of cardiac performance by intravenous infusion of l-arginine in patients with moderate congestive heart failure. J. Am. Coll. Cardiol. 1995, 26, 1251–1256.
    15. Yavuz, H.U.; Turnagol, H.; Demirel, A.H. Pre-exercise arginine supplementation increases time to exhaustion in elite male wrestlers. Biol. Sport 2014, 31, 187–191.
    16. Pahlavani, N.; Entezari, M.H.; Nasiri, M.; Miri, A.; Rezaie, M.; Bagheri-Bidakhavidi, M.; Sadeghi, O. The effect of l-arginine supplementation on body composition and performance in male athletes: A double-blinded randomized clinical trial. Eur. J. Clin. Nutr. 2017, 71, 544–548.
    17. Bailey, S.J.; Winyard, P.G.; Vanhatalo, A.; Blackwell, J.R.; DiMenna, F.J.; Wilkerson, D.P.; Jones, A.M. Acute l-arginine supplementation reduces the O2 cost of moderate-intensity exercise and enhances high-intensity exercise tolerance. J. Appl. Physiol. 2010, 109, 1394–1403.
    18. Burtscher, M.; Brunner, F.; Faulhaber, M.; Hotter, B.; Likar, R. The prolonged intake of L-arginine-L-aspartate reduces blood lactate accumulation and oxygen consumption during submaximal exercise. J. Sports Sci. Med. 2005, 4, 314–322.
    19. Chang, C.K.; Chang Chien, K.M.; Chang, J.H.; Huang, M.H.; Liang, Y.C.; Liu, T.H. Branched-chain amino acids and arginine improve performance in two consecutive days of simulated handball games in male and female athletes: A randomized trial. PLoS ONE 2015, 10, e0121866.
    20. Abel, T.; Knechtle, B.; Perret, C.; Eser, P.; von Arx, P.; Knecht, H. Influence of chronic supplementation of arginine aspartate in endurance athletes on performance and substrate metabolism-a randomized, double-blind, placebo-controlled study. Int. J. Sports Med. 2005, 26, 344–349.
    21. Hiratsu, A.; Tataka, Y.; Namura, S.; Nagayama, C.; Hamada, Y.; Miyashita, M. The effects of acute and chronic oral l-arginine supplementation on exercise-induced ammonia accumulation and exercise performance in healthy young men: A randomised, double-blind, cross-over, placebo-controlled trial. J. Exerc. Sci. Fit. 2022, 20, 140–147.
    22. Jones, A.M. Dietary nitrate supplementation and exercise performance. Sports Med. 2014, 44, 35–45.
    23. Forbes, S.C.; Harber, V.; Bell, G.J. Oral L-arginine before resistance exercise blunts growth hormone in strength trained males. Int. J. Sport Nutr. Exerc. Metab. 2014, 24, 236–244.
    24. Streeter, D.M.; Trautman, K.A.; Bennett, T.W.; McIntosh, L.E.; Grier, J.W.; Stastny, S.N.; Hackney, K.J. Endothelial, cardiovascular, and performance responses to l-Arginine intake and resistance exercise. Int. J. Exerc. Sci. 2019, 12, 701.
    25. Kanaley, J.A. Growth hormone, arginine and exercise. Curr. Opin. Clin. Nutr. Metab. Care 2008, 11, 50–54.
    26. Manini, T.M.; Yarrow, J.F.; Buford, T.W.; Clark, B.C.; Conover, C.F.; Borst, S.E. Growth hormone responses to acute resistance exercise with vascular restriction in young and old men. Growth Horm. IGF Res. 2012, 22, 167–172.
    27. Ghigo, E.; Arvat, E.; Valente, F.; Nicolosi, M.; Boffano, G.M.; Procopio, M.; Bellone, J.; Maccario, M.; Mazza, E.; Camanni, F. Arginine reinstates the somatotrope responsiveness to intermittent growth hormone-releasing hormone administration in normal adults. Neuroendocrinology 1991, 54, 291–294.
    28. Zajac, A.; Poprzecki, S.; Zebrowska, A.; Chalimoniuk, M.; Langfort, J. Arginine and ornithine supplementation increases growth hormone and insulin-like growth factor-1 serum levels after heavy-resistance exercise in strength-trained athletes. J. Strength Cond. Res. 2010, 24, 1082–1090.
    29. Chromiak, J.A.; Antonio, J. Use of amino acids as growth hormone-releasing agents by athletes. Nutrition 2002, 18, 657–761.
    30. Lambert, M.I.; Hefer, J.A.; Millar, R.P.; Macfarlane, P.W. Failure of commercial oral amino acid supplements to increase serum growth hormone concentrations in male body-builders. Int. J. Sport Nutr. 1993, 3, 298–305.
    31. Campbell, B.; Roberts, M.; Kerksick, C.; Wilborn, C.; Marcello, B.; Taylor, L.; Nassar, E.; Leutholtz, B.; Bowden, R.; Rasmussen, C.; et al. Pharmacokinetics, safety, and effects on exercise performance of l-arginine alpha-ketoglutarate in trained adult men. Nutrition 2006, 22, 872–881.
    32. Wax, B.; Kavazis, A.N.; Webb, H.E.; Brown, S.P. Acute l-arginine alpha ketoglutarate supplementation fails to improve muscular performance in resistance trained and untrained men. J. Int. Soc. Sports Nutr. 2012, 9, 17.
    33. Hurst, H.T.; Sinclair, J.; Beenham, M.S. Influence of absolute versus relative l-arginine dosage on 1 km and 16.1 km time trial performance in trained cyclists. J. Sci. Cycl. 2014, 3, 2–8.
    34. Greer, B.K.; Jones, B.T. Acute arginine supplementation fails to improve muscle endurance or affect blood pressure responses to resistance training. J. Strength Cond. Res. 2011, 25, 1789–1794.
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    Subjects: Sport Sciences
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    Update Date: 02 Sep 2022
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      Nyawose, S.; Naidoo, R.; Naumovski, N.; Mckune, A.J. Effects of Amino Acids L-Arginine on Physical Performance. Encyclopedia. Available online: https://encyclopedia.pub/entry/26798 (accessed on 06 February 2023).
      Nyawose S, Naidoo R, Naumovski N, Mckune AJ. Effects of Amino Acids L-Arginine on Physical Performance. Encyclopedia. Available at: https://encyclopedia.pub/entry/26798. Accessed February 06, 2023.
      Nyawose, Siphamandla, Rowena Naidoo, Nenad Naumovski, Andrew J. Mckune. "Effects of Amino Acids L-Arginine on Physical Performance," Encyclopedia, https://encyclopedia.pub/entry/26798 (accessed February 06, 2023).
      Nyawose, S., Naidoo, R., Naumovski, N., & Mckune, A.J. (2022, September 01). Effects of Amino Acids L-Arginine on Physical Performance. In Encyclopedia. https://encyclopedia.pub/entry/26798
      Nyawose, Siphamandla, et al. ''Effects of Amino Acids L-Arginine on Physical Performance.'' Encyclopedia. Web. 01 September, 2022.
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