ossido nitrico

Nitric oxide and sport: a possible correlation

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Over the last 25 years, nitric oxide – often simply referred to using its chemical formula NO – has definitely come to the fore in scientific research.

There is good reason for this. It is a mediator for biological processes, offering many benefits, including influencing vascular control, long-term memory, tissue inflammation and erectile dysfunction, not to mention its antioxidant action.


And this is merely the beginning. Endothelial NO is also a powerful vasodilator able to regulate blood pressure and delay atherosclerosis by inhibiting the recruitment of pro-inflammatory cytokines and platelet aggregation.

What is nitric oxide?

So, what is nitric oxide? In short, it is a free radical.  We could add it is a free radical synthesised by enzymes called NO-synthases (NOS). These belong to the oxygenase group and have a similar structure to cytochrome P450. These enzymes synthesise NO from L-arginine.


Nitric oxide can also “boast” a prestigious award. In 1998, studies on its action won Prof. Salvador Moncada and co. the Nobel prize.

Nitric oxide and skeletal muscle

Recent research has often focused on the functional importance of nitric oxide on skeletal muscle.

Recent studies have shown that skeletal muscle produces NO continuously. It acts as an endogenous physiological factor with a modulating action both on tissues and cells.  NO influences the metabolism and contractile function of muscles by acting directly on muscle fibres.

Additionally, the muscle-skeletal functions regulated by NO, or by molecules correlated to it, include producing power (excitation-contraction coupling), regulating blood flow, differentiating myocites, i.e. muscle fibers, breathing and glucose homeostasis.

A table to learn more about NO

The table below lists the characteristics of three NOS isoforms (i.e. the protein molecule with the same function, but with some structural differences, Ed. note).


The expression and localisation of NOS isoforms depend on numerous variables: age, development, innervation and muscle activity, exposure to cytokines and growth factors, muscle fibre type and species.

Nitric oxide synthase (NOS) isoforms in skeletal muscles


NOS isoform Type I Type II Type III
Alternative name Neuronal Inducible Endothelial
Molecular weight 160 kDal 130 kDal 130 kDal
Production stimulus Exercise Cytokines Exercise
Localisation on the myocyte Sarcolemma Intracellular fluid Mitochondrion
Specific fibre type Quick fibres Not tested No
Expression on other cell types Axon Macrophages Vascular Endothelium
Regulation of enzymatic activity Ca2+ – Calmodulin Transcription Ca2+ – Calmodulin
NO synthesis pattern Low rate, intermittent High rate, continuous Low rate, intermittent
Physiological role Muscle contraction mediator

Cell-cell interactions

Antimicrobial action Modulating action on mitochondrial respiration (?)


The effects of nitric oxide on muscle energy tend to preserve intracellular energy reserves.  This has an impact on the metabolism of myocytes at various levels, by promoting glucose transport while inhibiting glycolysis, mitochondrial respiration and the breaking down of creatine phosphate.

All of this translates into more efficiency thanks to the diminished energy cost of exercise (less need for oxygen that becomes more available), more exercise tolerance and more efficient recovery times.

In truth, NOS-independent NO production is also possible. This comes from the need to have fundamental NO synthesis precursors available in the form of food or supplements.  The nitrates and nitrites were the first to produce notable results on this front.

Nitric oxide and sports supplements

Supplements are on the rise in professional and amateur sport. Why? Simple: they improve performance and recovery. Many athletes, especially body-builders and those in strength disciplines, take pre-workout supplements.


Such products generally contain a mix of ingredients, stimulants (e.g. caffeine), energy production boosters (like creatine) or substances that amplify hydrogen ions (such as beta-alanine). Other supplements contain nutrients and protein-based preparations for recovery , antioxidants and nitric oxide precursors (e.g. arginine).


Recently, a whole new class of sports supplements has come to the fore, namely the NO boosters that aim to increase (in theory!) nitric oxide. The best known is “L-arginine”. This class of supplements is based on the correlation between an increase in circulating NO and improved performance and post-exercise recovery.


frutto del cacao

From creatine to flavanols in cocoa: focal areas for study

Hundreds of studies have tested isolated ingredients commonly used pre-workout.  Many have provided positive results. Let’s look at caffeine. Taking some before exercising appears to improve both aerobic and anaerobic performance, although the results are controversial. Most studies used a pre-exercise dosage of 3 to 7 mg/kg. But some used higher quantities.


Creatine is another well-studied nutrient, used to improve performance during high-intensity exercise. In most studies, the dosage was 5 grams per day, for several days/weeks until the required stress test is done. Beta-alanine has also attracted a great deal of interest. This heavily debated amino acid remains somewhat contentious when it comes to agreeing whether it actually does reduce lactate-acid build up and/or improve performance.


Recently, glycine propionyl-l-carnitine was found to improve performance and reduce the production of lactate during a set of sprints when it was taken as a single dosage of 4.5 grams. An increase in NO was also reported (measured as nitrates and nitrites) when a group of participants took glycine propionyl-l-carnitine at a daily dosage of 4.5 grams for 4 or 8 weeks.   


In the natural supplement category, in addition to organic nitrates (today perhaps the most studied group of NO inducers), cocoa flavanols are attracting quite a lot of interest.

A very interesting study showed the potential synergy between cocoa flavanols and nitrates when it comes to NO induction.

Earlier research detected that flavanols in general and cocoa flavanols in particular have a specific action on NO-dependent vascular endothelial function.


In short

The data from scientific research tends to be about individual ingredients, but using these in separate preparations is hardly productive.  I feel a real boost for muscle energy should be sought in the synergistic action of exogenous substances able to activate NO production, regardless of the NOS activities. At least, that’s how I see things.



  • Moncada S, Higgs EA. The L-arginine-nitric oxide pathway. N Engl J Med. Dec 30;329(27):2002-12.
  • Brown GC. Nitric oxide regulates mitochondrial respiration and cell functions by inhibiting cytochrome oxidase. FEBS Lett. 1995 Aug 7;369(2-3):136-9.
  • Jacobs PL, Goldstein ER, Blackburn W, Orem I, Hughes JJ. Glycine propionyl-L-carnitine produces enhanced anaerobic work capacity with reduced lactate accumulation in resistance trained males. J Int Soc Sports Nutr. 2009 Apr 2;6:9.
  • Heiss C, Schroeter H, Balzer J, Kleinbongard P, Matern S, Sies H, Kelm M. Endothelial function, nitric oxide, and cocoa flavanols. J Cardiovasc Pharmacol. 2006;47 Suppl 2:S128-35; discussion S172-6.
  • Bailey SJ, Winyard P, Vanhatalo A, Blackwell JR, DiMenna FJ, Wilkerson DP, Tarr J, Benjamin N, Jones AM. Dietary nitrate supplementation reduces the O2 cost of low-intensity exercise and enhances tolerance to high-intensity exercise in humans. J Appl Physiol. 2009 Oct; 107 (4):1144-1155.

A nutritional biologist, he holds degrees in Pharmacy, Dietetics and the Science of Human Nutrition. He is a member of the Governing Body of SINSeB, the Italian sports nutrition and wellness association, a consultant to the Italian national volleyball and beach volleyball teams and he is involved with the research and study division of the Boxing Federation. Since 2005, he has been a lecturer for the Movement Science Degree Course at the Tor Vergata - University of Rome's Medical Faculty. For the Olympics in Beijing in 2008, London in 2012 and Rio in 2016, he oversaw weight loss for athletes during the national trials for the Italian Federation of Judo, Karate and Martial Arts, the Italian Boxing Federation, and the Italian Weightlifting Federation