Pre-Workout Nitric Oxide – Does it Really Work?

Pre-workout drinks which raise the levels of nitric oxide (NO) in your system are a craze with gym goers and athletes alike. The reason – the so called ‘pump’ you get when doing typical bodybuilding exercises combined with the ability to ‘rep out’ a few more on all exercises.

Contrary to anecdotal evidence, however, there is not much published research on the alleged effects of ‘pre-workout’ intake of NO.

The question to be asked is: do pre-workout supplements really bump up your blood NO levels? And, are they worth spending your hard-earned money on!

Let us investigate!

Chemistry of Nitric Oxide

Nitric oxide or NO for short is a chemical released by the innermost layers of your blood vessels – the endothelium; main function it serves is causing relaxation of the blood vessel walls resulting. This causes increased blood supply to the concerned organ or tissue.

Not surprising then that NO is also known as the ‘endothelium derived relaxing factor’ (EDRF) (Furchgott & Zawadzki, 1980).

NO is synthesized from the amino acid l-arginine; the process requires the presence of oxygen, enzymes and co-factors like vitamins (Collier & Vallance, 1991). Thus, arginine (being the precursor of NO) is present in most pre-workout NO boosting supplement formulations.

Physiological Roles of Nitric Oxide

Some of the important physiological functions that nitric oxide serves are as follows (Thomas et al., 2008; Anderson, 2000; Salanova, Schiffl, Puttmann, Schoser, & Blottner, 2008):

  • Increases blood flow owing to the relaxation of blood vessel walls (Furchgott & Zawadzki, 1980)
  • Improved resistance to development of angina and other peripheral arterial diseases
  • Enhances immune function (with decreased stickiness of the white blood cells as well as platelets)

Role of Nitric Oxide in Enhancing Exercise Capacity

A number of research studies have strongly suggested that exercise is associated with increase in plasma levels of NO. Based on prevalent research proof, it can be safely said that NO levels are enhanced both during as well as after an exercise session. Furthermore, this finding is consistent with an acute exercise session (Bode-Boger, Boger, Schroder, & Frolich, 1994; Clarkson et al., 1999; Rognmo et al., 2008) as well as with training lasting for a few days a week for several weeks (Edwards et al., 2004; Poveda et al., 1997; Tordi et al., 2006). In addition, regular training has shown to enhance the resting blood levels of nitric oxide – thus, conditioned exercisers and athletes will have higher resting levels of NO in their blood as compared to sedentary people.

No wonder then that regular exercise and improved resting blood levels of NO result in a number of benefits:

  • Enhanced exercise capacity
  • Improved neurotransmission which enhances force of muscle contraction
  • Hypertrophy of skeletal muscle fibres
  • Better recovery post-workout (owing, partly to the increased supply of nutrients secondary to increased blood flow)

Rationale Behind the Use of NO Enhancing Supplements

Nitric oxide enhancing supplements (containing precursors of NO like arginine alpha-ketoglutarate or AAKG) are popular amongst regular exercisers. The associated ‘pump’ as well as the increased exercise capacity (in terms of throwing in a ‘couple of more repetitions’ due to flushing out of lactic acid) is what really excites athletes and ‘gym rats’.

As mentioned earlier, there are definite health and fitness benefits of improving resting levels of NO – either by training alone or combining training with NO enhancing supplements; a fact that is supported strongly by research as well as anecdotal evidence.

Supplements enhancing NO levels typically contain the precursor amino acid arginine either as AAKG or some other salt of arginine like l-arginine nitrate. In addition to arginine, pre-workout proprietary formulations contain ingredients for improving mental focus and energy levels during workouts and for effective recovery post-workout – some of these are creatine, caffeine, synephrine, taurine and beta-alanine, amongst others.

A relatively newer addition to drugs that enhance NO levels in blood is glycine propionyl-l-carnitine (GPLC). GPLC is made up of amino acid glycine (combined with propionyl-l-carnitine). As little as 4.5g of GPLC a day has been shown to cause increased NO levels in both sedentary (Bloomer, Tschume, & Smith, 2009) as well as trained men (Bloomer, Smith, & Fisher-Wellman, 2007; Smith, Fry, Tschume, & Bloomer, 2008). As opposed to arginine or its salts like AAKG, GPLC also increases the enzymes responsible for NO synthesis – chiefly, endothelial nitric oxide synthase (eNOS) further adding to the NO enhancing action (de Sotomayor, Mingorance, Rodriguez-Rodriguez, Marhuenda, & Herrera, 2007). Furthermore, the ability of GPLC to increase plasma levels of NO has been definitely proved by researchers (Bloomer et al., 2007; Bloomer et al., 2009) – in comparison to arginine or AAKG where the research proof is lacking.

Thus, a product containing GPLC is a much better bet if you are looking to derive the amazing training benefits of enhanced blood levels of NO.


Although, there is lack of evidence for the amazing benefits of NO enhancing supplements, anecdotal evidence is strong, to say the least. All those who have used such products do indeed swear by their effectiveness.

Furthermore, addition of newer ingredients is turning the argument against NO enhancers into a very weak one. If you are still in doubt, the best way to find out is to use one!

Reference List

Anderson, J. E. (2000). A role for nitric oxide in muscle repair: nitric oxide-mediated activation of muscle satellite cells. Mol.Biol.Cell, 11, 1859-1874.

Bloomer, R. J., Smith, W. A., & Fisher-Wellman, K. H. (2007). Glycine propionyl-L-carnitine increases plasma nitrate/nitrite in resistance trained men. J Int Soc Sports Nutr., 4, 22.

Bloomer, R. J., Tschume, L. C., & Smith, W. A. (2009). Glycine propionyl-L-carnitine modulates lipid peroxidation and nitric oxide in human subjects. Int J Vitam.Nutr.Res., 79, 131-141.

Bode-Boger, S. M., Boger, R. H., Schroder, E. P., & Frolich, J. C. (1994). Exercise increases systemic nitric oxide production in men. J Cardiovasc.Risk, 1, 173-178.

Clarkson, P., Montgomery, H. E., Mullen, M. J., Donald, A. E., Powe, A. J., Bull, T. et al. (1999). Exercise training enhances endothelial function in young men. J Am Coll.Cardiol, 33, 1379-1385.

Collier, J. & Vallance, P. (1991). Physiological importance of nitric oxide. BMJ, 302, 1289-1290.

de Sotomayor, M. A., Mingorance, C., Rodriguez-Rodriguez, R., Marhuenda, E., & Herrera, M. D. (2007). l-carnitine and its propionate: improvement of endothelial function in SHR through superoxide dismutase-dependent mechanisms. Free Radic.Res., 41, 884-891.

Edwards, D. G., Schofield, R. S., Lennon, S. L., Pierce, G. L., Nichols, W. W., & Braith, R. W. (2004). Effect of exercise training on endothelial function in men with coronary artery disease. Am J Cardiol, 93, 617-620.

Furchgott, R. F. & Zawadzki, J. V. (1980). The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature, 288, 373-376.

Poveda, J. J., Riestra, A., Salas, E., Cagigas, M. L., Lopez-Somoza, C., Amado, J. A. et al. (1997). Contribution of nitric oxide to exercise-induced changes in healthy volunteers: effects of acute exercise and long-term physical training. Eur J Clin Invest, 27, 967-971.

Rognmo, O., Bjornstad, T. H., Kahrs, C., Tjonna, A. E., Bye, A., Haram, P. M. et al. (2008). Endothelial function in highly endurance-trained men: effects of acute exercise. J Strength Cond.Res., 22, 535-542.

Salanova, M., Schiffl, G., Puttmann, B., Schoser, B. G., & Blottner, D. (2008). Molecular biomarkers monitoring human skeletal muscle fibres and microvasculature following long-term bed rest with and without countermeasures. J Anat., 212, 306-318.

Smith, W. A., Fry, A. C., Tschume, L. C., & Bloomer, R. J. (2008). Effect of glycine propionyl-L-carnitine on aerobic and anaerobic exercise performance. Int J Sport Nutr.Exerc.Metab, 18, 19-36.

Thomas, D. D., Ridnour, L. A., Isenberg, J. S., Flores-Santana, W., Switzer, C. H., Donzelli, S. et al. (2008). The chemical biology of nitric oxide: implications in cellular signaling. Free Radic.Biol.Med, 45, 18-31.

Tordi, N., Colin, E., Mourot, L., Bouhaddi, M., Regnard, J., & Laurant, P. (2006). Effects of resuming endurance training on arterial stiffness and nitric oxide production during exercise in elite cyclists. Appl.Physiol Nutr.Metab, 31, 244-249.

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Dr. Deepak S Hiwale

Dr. Deepak S Hiwale, a.k.a "The Fitness Doc" specializes in sports medicine in addition to being an elite personal trainer. He currently runs an elite personal training company in West London. As a sports injury and fitness writer-presenter, he tries to disseminate as much knowledge as possible for the benefit of all. MBBS (University of Pune); MSC, Sports and Exercise Medicine (University of Glasgow); Diploma in Personal Training (YMCA Dip. PT, London).

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