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NITRIC OXIDE - Effects on Exercise Performance and Training Adaptation

Brian Turner

Posted on September 08 2014

The signaling molecule nitric oxide (NO) is best known for its ability to enhance performance by increasing blood flow to muscle tissue. The increase in blood flow brings more essential nutrients and oxygen to laboring muscles while simultaneously removing metabolic waste, thus improving muscular function and endurance. NO triggers increased blood flow by turning on cellular signaling cascades that relax the smooth muscle within the arterial wall, causing the arteries to dilate or open up, permitting greater blood flow.

Nitric Oxide Also Boosts Muscle Growth While Trimming Body Fat

In addition to regulating blood flow, NO has emerged as an essential regulator of several additional functions that also improve the overall response to exercise.1 In particular, NO has surfaced as an important regulator of body composition by enhancing the anabolic effects of insulin for greater muscle mass. In addition, NO has the capacity to lower body fat by effectively increasing fatty acid oxidation. In fact, several studies have shown that supplementation with compounds that trigger NO production increases muscle mass while decreasing body fat.2-4 Furthermore, additional studies in animals have shown that NO-boosting compounds can also activate a process known as thermogenesis,5,6 which increases energy expenditure, further promoting the loss of body fat.

Boost NO with AML Preworkout

Because of the remarkable ability of NO to increase muscle and cut fat, Advanced Molecular Labs and its CEO Steve Blechman have brought together an impressive blend of compounds that boosts NO production like never seen before in the revolutionary new product AML Preworkout. The considerable spike in NO levels induced by AML Preworkout will most assuredly drive astonishing gains in lean body mass and muscular endurance.

Citrulline More Potently Increases NO production and Cardiovascular Performance

NO is biosynthesized from the amino acid arginine, which originally led to the belief that increased arginine consumption would enhance production of NO. However, it turns out that arginine is poorly absorbed by the intestine7 and quickly broken down by the liver,8 which together significantly reduces its capacity to increase NO production, making it a rather poor choice for increasing NO. On the other hand, the amino acid citrulline, which is converted in the body into arginine, is readily absorbed by the intestines and is not rapidly degraded by the liver,9 making citrulline a much more effective way to increase endogenous NO production for improved muscular performance.
The greater influence of citrulline on NO levels relative to arginine was clearly demonstrated in a study by Osowska et al.10 where they found that citrulline consumption produced a substantially larger amount of arginine in the blood and muscle tissue when compared to either arginine or placebo ingestion. In addition, another study by Schwedhelm et al.11 showed that the capacity of citrulline to yield higher levels of arginine in the body also triggered improved production of NO along with NO-dependent signaling activity. Collectively, these studies confirm that citrulline supplementation is considerably more effective than arginine for boosting NO production and function.

AML Preworkout’s ATP Also Triggers NO Production

ATP normally functions as the primary energy source within the body. More recently however, ATP has been shown to exhibit other functions in the body that are not related to energy production yet still enhance exercise performance. One of these additional functions occurs when ATP binds to a specific set of adenosine receptors embedded within the cell membrane, initiating a set of cellular signaling cascades that trigger the production of NO.
What's more, studies have shown that ATP ingestion stimulates the formation of NO, resulting in the increase of blood flow14-15 while another study by Rathmacher et al.16 confirmed that the consumption of 400 milligrams of ATP per day for two weeks significantly increased muscular endurance, particularly for the last two sets of a peak-torque endurance test using a dynamometer.

More NO Boosters for Muscle Size and Function

In addition to the previously mentioned NO-boosters, AML Preworkout possesses watermelon and grape skin extracts, which are also loaded with compounds that powerfully stimulate NO production17-18 for an even greater influence on muscle growth and performance enhancement.

Bolstering NO Catalysis

The biosynthesis of NO from arginine is catalyzed by the enzyme nitric oxide synthase. This group of enzymes requires the cofactor tetrahydrobiopterin (BH4) to catalytically produce NO. Consequently, it was first believed that BH4 intake would boost NO production by supporting greater levels of nitric oxide synthase activity. However, studies have shown that BH4 intake failed to show any significant improvement in NO production or vasodilation due to the poor bioavailability of BH4.19-20
The inability of BH4 to boost the concentration of NO led to alternate approaches, which included the use of folic acid, as it was discovered that orally consuming folic acid, a cofactor involved in the biosynthesis of BH4, effectively improved NO production and vasodilation.21 This was presumably due to an increase in the biosynthesis of BH4 that ultimately supported greater nitric oxide synthase production of NO.
In summary, the impressive combination of compounds in AML Preworkout uniquely increase the production of the ergogenic molecule NO by supplying an abundance of diverse NO precursors while simultaneously triggering the sustained enzymatic activity of the enzymes that catalyze NO production. Altogether, this multifaceted approach generates a robust biochemical environment that leads to the copious production of NO, which stimulates greater blood flow to your muscles all while enhancing the anabolic response to training for superior gains in muscle mass and performance.

For most of Michael Rudolph’s career he has been engrossed in the exercise world as either an athlete (he played college football at Hofstra University), personal trainer or as a Research Scientist (he earned a B.Sc. in Exercise Science at Hofstra University and a Ph.D. in Biochemistry and Molecular Biology from Stony Brook University). After earning his Ph.D., Michael investigated the molecular biology of exercise as a fellow at Harvard Medical School and Columbia University for over eight years. That research contributed seminally to understanding the function of the incredibly important cellular energy sensor AMPK— leading to numerous publications in peer-reviewed journals including the journal Nature. Michael is currently a scientist working at the New York Structural Biology Center doing contract work for the Department of Defense on a project involving national security.

References:

1. Hill, B.G., Dranka, B.P., Bailey, S.M., Lancaster, J.R., Jr., and Darley-Usmar, V.M. (2010). What part of NO don't you understand? Some answers to the cardinal questions in nitric oxide biology. J Biol Chem 285, 19699-19704.
2. Wascher, T.C., Graier, W.F., Dittrich, P., Hussain, M.A., Bahadori, B., Wallner, S., and Toplak, H. (1997). Effects of low-dose L-arginine on insulin-mediated vasodilatation and insulin sensitivity. Eur J Clin Invest 27, 690-695.
3. Sansbury, B.E., and Hill, B.G. (2014). Regulation of obesity and insulin resistance by nitric oxide. Free Radic Biol Med 73C, 383-399.
4. Lucotti, P., Setola, E., Monti, L.D., Galluccio, E., Costa, S., Sandoli, E.P., Fermo, I., Rabaiotti, G., Gatti, R., and Piatti, P. (2006). Beneficial effects of a long-term oral L-arginine treatment added to a hypocaloric diet and exercise training program in obese, insulin-resistant type 2 diabetic patients. Am J Physiol Endocrinol Metab 291, E906-912.
5. Jobgen, W., Meininger, C.J., Jobgen, S.C., Li, P., Lee, M.J., Smith, S.B., Spencer, T.E., Fried, S.K., and Wu, G. (2009). Dietary L-arginine supplementation reduces white fat gain and enhances skeletal muscle and brown fat masses in diet-induced obese rats. J Nutr 139, 230-237.
6. Tan, B., Yin, Y., Liu, Z., Li, X., Xu, H., Kong, X., Huang, R., Tang, W., Shinzato, I., Smith, S.B., and Wu, G. (2009). Dietary L-arginine supplementation increases muscle gain and reduces body fat mass in growing-finishing pigs. Amino Acids 37, 169-175.
7. Grimble, G.K. (2007). Adverse gastrointestinal effects of arginine and related amino acids. J Nutr 137, 1693S-1701S.
8. Heyland, D.K., Dhaliwal, R., Drover, J.W., Gramlich, L., and Dodek, P. (2003). Canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients. JPEN J Parenter Enteral Nutr 27, 355-373.
9. Cynober, L. (2007). Pharmacokinetics of arginine and related amino acids. J Nutr 137, 1646S-1649S.
10. Osowska, S., Moinard, C., Neveux, N., Loi, C., and Cynober, L. (2004). Citrulline increases arginine pools and restores nitrogen balance after massive intestinal resection. Gut 53, 1781-1786.
11. Schwedhelm, E., Maas, R., Freese, R., Jung, D., Lukacs, Z., Jambrecina, A., Spickler, W., Schulze, F., and Boger, R.H. (2008). Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. Br J Clin Pharmacol 65, 51-59.
12. Bailey, S.J., Fulford, J., Vanhatalo, A., Winyard, P.G., Blackwell, J.R., DiMenna, F.J., Wilkerson, D.P., Benjamin, N., and Jones, A.M. (2010). Dietary nitrate supplementation enhances muscle contractile efficiency during knee-extensor exercise in humans. J Appl Physiol (1985) 109, 135-148.
13. Cermak, N.M., Gibala, M.J., and van Loon, L.J. (2012). Nitrate supplementation's improvement of 10-km time-trial performance in trained cyclists. Int J Sport Nutr Exerc Metab 22, 64-71.
14. Parker, J.C. (1970). Metabolism of external adenine nucleotides by human red blood cells. Am J Physiol 218, 1568-1574.
15. Schrader, J., Berne, R.M., and Rubio, R. (1972). Uptake and metabolism of adenosine by human erythrocyte ghosts. Am J Physiol 223, 159-166.
16. Rathmacher, J.A., Fuller, J.C., Jr., Baier, S.M., Abumrad, N.N., Angus, H.F., and Sharp, R.L. (2012). Adenosine-5'-triphosphate (ATP) supplementation improves low peak muscle torque and torque fatigue during repeated high intensity exercise sets. J Int Soc Sports Nutr 9, 48.
17. Breese, B.C., McNarry, M.A., Marwood, S., Blackwell, J.R., Bailey, S.J., and Jones, A.M. (2013). Beetroot juice supplementation speeds O2 uptake kinetics and improves exercise tolerance during severe-intensity exercise initiated from an elevated metabolic rate. Am J Physiol Re gul Integr Comp Physiol 305, R1441-1450.
18. Resende, A.C., Emiliano, A.F., Cordeiro, V.S., de Bem, G.F., de Cavalho, L.C., de Oliveira, P.R., Neto, M.L., Costa, C.A., Boaventura, G.T., and de Moura, R.S. (2014). Grape skin extract protects against programmed changes in the adult rat offspring caused by maternal high-fat diet during lactation. J Nutr Biochem 24, 2119-2126.
19. Moens, A.L., Kietadisorn, R., Lin, J.Y., and Kass, D. (2011). Targeting endothelial and myocardial dysfunction with tetrahydrobiopterin. J Mol Cell Cardiol 51, 559-563.
20. Alkaitis, M.S., and Crabtree, M.J. (2012). Recoupling the cardiac nitric oxide synthases: tetrahydrobiopterin synthesis and recycling. Curr Heart Fail Rep 9, 200-210.
21. Youn, J.Y., Gao, L., and Cai, H. (2012). The p47phox- and NADPH oxidase organiser 1 (NOXO1)-dependent activation of NADPH oxidase 1 (NOX1) mediates endothelial nitric oxide synthase (eNOS) uncoupling and endothelial dysfunction in a streptozotocin-induced murine model of diabetes. Diabetologia 55, 2069-2079.