Nitric oxide and sport: a possible correlation
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.
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|
|Molecular weight||160 kDal||130 kDal||130 kDal|
|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
|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.
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.
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.
Earlier research detected that flavanols in general and cocoa flavanols in particular have a specific action on NO-dependent vascular endothelial function.
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.