Your Nitric Oxide Pre-workout may not be as explosive as you think



Insanely vascular forarms of Bodybuilding Legend Marco Viviani

Since the discovery and publication of the potential ergogenic of nitric oxide, the dietary supplement industry raged in the creation and marketing of formulas claiming to increase its the production of this powerful signaling molecule. However, the following paragraphs will reveal to you that few are the products that successfully accomplished this feat.

What is nitric oxide (N=O)

Nitric Oxide (NO), a molecule consisting of one atom of nitrogen and one atom of oxygen, is a soluble gas is produced in the body which acts as an endogenous messenger (used by the body to communicate with other cells in the body).

Nitric oxide is formed in healthy vascular endothelium through. This occurs when the amino acid L-Arginine is converted into L-citruline by three isomeric forms of the Nitric Oxide Synthase (NOS) enzymes using oxygen and L-Arginine.

Benefits of NO

NO has multiple positive physiologic effects including vasodilation, adrenaline and GRH (hormone stimulating release of anabolic hormones) release, and glucose uptake.

Heart and muscle protection

In 1998, Robert F Furchgott, Louis J. Ignarro, and Fend Murad were awarded the Nobel Prize in medicine for their discoveries concerning nitric oxide as a vasodilating signaling molecule. Furthermore, NO lowers blood pressure during exercise (Am J Physiol Heart Circ Physiol 273:H405–H410), providing a cardioprotective effect. This is especially beneficial to bodybuilders using substances increasing blood pressure. NO donor has also been proven to protect the contractile function of skeletal muscle from reperfusion injury.

Other health or lifestyle benefits include harder and larger penile erections (the popular erectile dysfunction drug sildenafil citrate, Viagra prevents the breakdown of cGMP produced by NO following sexual stimulation by inhibiting PDE5 enzyme), as well as improved sexual sensations and performance.

Nitric oxide relevance in sports

Muscle contraction and strength

Nitric oxide causes doubling of force through S-nitrolylation of cysteine of the myosin heavy chains – Pflügers Arch 434:242–245. Nitrosylation acts as a molecule gear shift for myosin. NO also supports muscle contraction by increasing total content of calcium (key element of muscle contraction) in muscle, and by triggering a muscle “gear shift”. Meszaros et al. demonstrated that NO attenuates calcium (essential element of muscle contraction) release from muscles by modulating the activity of the RyR/calcium release channel.

NO mediates muscle growth

NO is a mediator of muscle hypertrophy along with insulin-like growth factor (IGF-1), mechano growth factors (MGFs) and angiotensin II (angiotensin II is necessary for optimal overload-induced skeletal muscle hypertrophy). NO seems to promote such muscle hypertrophy by increasing glucose / insulin uptake as well as activation of satellite cells. Nitric oxide also activates the release of hepatocyte growth factor (HGF) seems to be responsible for migration of satellite cells to the injured areas.

A 2005 research study in the Journal Applied Physiology demonstrated that nitric oxide synthase by the NOS (nitric oxide synthase enzyme) is required for upregulation of genes involved in muscle hypertrophy and contractile function (i.e. actin and type I myosin heavy chain).

Both actin (the main constituent of the thin filaments of muscle fibers) and type I myosin heavy chain (a protein found in muscle fibers involved in muscle contraction) generally increase during muscle overload mediated muscle hypertrophy. However, it has been demonstrated that muscle which were induced hypertrophy using functional overload had an approximate 50 percent reduction in muscle protein accumulation as well as a complete inhibition of actin and type I (slow fiber) myosin heavy chain when administered a NO inhibitor while the normal group had a 45 percent increase in muscle protein accumulation, a 90 percent increase in skeletal muscle actin mRNA, and a 140 percent increase in type I muscle fiber myosin heavy chain mRNA.

NO supports optimal strength

Skeletal muscles exert their effect on the environment by shortening and pulling on segments (bones) to which they are attached. Such shortening is accomplished by the relative movement of millions of their myosin and actin contractile proteins.

Nitric oxide directly regulates muscle contraction by direct action on such myosin contractile proteins as well as through activation of guanylyl cyclase to generate cGMP. Nitric oxide has been shown to cause a molecular “gear shift” via S-nitrosylation of cysteines in the myosin (contractile protein) heavy chain. This gear shift doubles the force generated by the contractile proteins and double its contraction time (ton). Thus, the doubling of ton with no change in the detached time (toff) results in a 50% decrease in actin filament velocity as well as an approximate 2X increase in average force. Additionally, scavenges super oxides which limit force production.

However, when using a load of 50% of 1RM (sets 7-9), repetitions number was 6.2% higher for the gel compared to placebo.

NO increases Maximum Velocity of Shortening

Three studies by two groups establish that skeletal muscle NOS in mice and rats augments Muscle Velocity Shortening (MVS). In fact, analogs of cGMP increased MVS by 17%, and intracellular increases in cGMP (via activity modulation of the RyR/calcium release channel) probably accounts for at most 50% of the NO effect.

The addition of a NO donor such as the one used in TORQUE has been proven to significantly reduce calcium release and increase cGMP.

NO increases cell nutrition

NO effectively improve cell nutrition by acting as a potent vasodilator as well as promoting angiogenesis (growth of new blood vessels from pre-existing blood vessels) via up regulation of Vascular Endothelial Growth Factors (VEGFs).

During exercise, norepinephrine is released which is a potent vasoconstrictor of vascular smooth muscle. The sympathetic nervous activity increases with the contractile activity of muscle as well as with the muscle mass utilized. Skeletal muscle needs nitric oxide, a potent vasodilator, to compensate for this constriction. In fact, there is good evidence that insulin-mediated vasodilation is partly NO dependent and that nitric oxide donors, such as TORQUE® therefore increases glucose uptake.

Nitric Oxide increases endurance

Intense skeletal muscle activity leads to a decline in muscle performance, which is known as fatigue. Nitric oxide has been shown to sustain performance by protecting against a decline in muscle function resulting from excitation-contraction coupling (training). TORQUE® has been shown to increase the number of repetition by 6.2% after a single topical administration.

Nitric oxide helps protect and heal tendons and ligaments

Nitric oxide plays a valuable role in tendon healing due to its ability to increase blood flow and increase collagen production.

NO inscreases fat loss

Another 2005 article from Biochemical and Molecular Aspects of Nutrition, demonstrated that obese and insulin intolerant rats had an enhanced production of four genes responsible for fatty acid oxidation in adipose tissue when their nitric oxide production were increased.

In sports, the above benefits translate into muscle growth, increasing strength, increasing Maximum Velocity of Shortening (MVS) improvement, enhancing fat oxidation, increased endurance, as well as many positive cardiovascular effects.

Nitric oxide has initially captured the attention of the bodybuilding industry (due to its ability to immediately improve muscle pump), and more recently the endurance sports.

Vascularity, cell nutrition and sports performance

Nitric oxide increases apparent vascularity in lean muscular athletes as well as facilitates muscle recovery by increasing cell nutrition, oxygen transport and better elimination of muscle contraction metabolic bi products through vasodilation (increased diameter of blood vessels) as well as angiogenesis, or development of new blood vessels by up regulation the gene expression of VEGF (Vascular endothelial growth factor). Additionally, insulin mediated vasodilation as well as glucose transport is dependant of nitric oxide. Young and Leighton (J Appl Physiol 82:359–363.) found that cGMP a analog (which is increased by NO) increases glucose transport and oxidation. This is mainly caused by increased insulin sensitivity (Clin Sci 94:175–180), as well as calcium/contraction and phosphatidylinositol-3-kinase-independent pathway (Diabetes 46:1915–1919). This leads to improved performance as well as increased glucose use.

Muscle recovery

NO supports post effort muscle recovery by limiting calcium release from muscle cells – Acta Physiol Scand 162:285–293.

The marketing hype of L-Arginine, Citrulline and other Nitric Oxide Precursors

Nitric oxide is naturally produced by the Nitric Oxide Synthase (NOS) enzymes using oxygen and L-Arginine. Dietary supplements aimed at increasing blood nitric oxide are heavily marketed and represents a multi-million dollars per year industry. Unfortunately, there exists little published scientific evidence that these products deliver the results claimed by advertisements. In fact, most pre-workout dietary supplements consist of L-arginine, Citrulline and/or other NO precursors along with other metabolic ingredients and falsely pretend (without any clinical research) to increase nitric oxide production. It is essential to know that:

  • 50 to 70 percent of dietary arginine and other nitric oxide precursors are metabolized by the intestinal mucosa and don’t enter circulation due to their extensive catabolism in the small intestines
  • A significant portion of the absorbed L-Arginine is:
    • Destroyed by the arginase enzyme
    • Used to create proteins

Only a small fraction of the consumed L-Arginine or other nitric oxide precursors such as Citrulline are converted into nitric oxide and reach the intended destination – the muscle. In fact, there are no scientific studies demonstrating a significant increase of muscle nitric oxide levels after consumption a nitric oxide precursor such as arginine or Citrulline.

Furthermore, a major portion of the supplemental arginine ingested and absorbed by individuals with a condition called NOS SNP (nitric oxide synthase single nucleotide polymorphisms) will be converted into peroxynitrite (instead of nitric oxide), which is highly reactive and health damaging.

Finally, supplemental arginine has been shown to promote outbreak of dormant herpes virus. This is a very sad thing for the near 90% of north American population affected with HVS-1 (buccal herpes), and the near 40% of population carrying HVS-2 (genital herpes).

In other words, unless you are seeking to suffer from accelerated aging or illness caused by production of peroxynitrite, or from herpes outbreak, don’t waste your money on arginine-based supplements falsely claiming to effectively boost nitric oxide levels.

Can you benefit from the power of nitric oxide?

Nitric oxide is an extremely powerful molecule which only needs to be produced in tiny amounts (in the order of nanograms, or millionths of gram) to exert dramatic effects. It is important to know that the body has stores of all the necessary amino acids in the form of blood albumen and does not need supplemental arginine to produce the needed nitric oxide.

Now that you know that supplements based on citrulline, arginine, and other arginine derivatives claiming to boost nitric oxide are only gimmicks, you may ask yourself if there are other ways to optimize nitric oxide production when and where needed. The answer to your question is yes.

There exist several naturally occurring compounds which have been proven to effectively increase nitric oxide. Those include:

  • Muira Puama
  • Yohimbine
  • Rg3 and Rg6 Ginsenosides (from Ginseng)
  • Forskolin

However, another important fact to know is that the vast majority of active compounds included in dietary supplements are poorly absorbed – I mean often less than even 1%, as well as heavily metabolized in the gut and by the liver. This results in an often less than 1% bioavailability of such compounds.

Fortunately, a handful of reputable companies (such as WARMEDS) are using revolutionary liposome delivery technologies to increase by tens of folds the absorption of valuable medicinal ingredients.


 Bodybuilding Legend Marco Viviani in action

In conclusion, if you don’t want to waste your money, or worst damage your health, it is important to opt for proven active ingredients carried out using effective delivery technologies.

About the Author

Pierre Vinet is a Master Trainer who graduated in Biochemistry at Quebec University, and continued post graduate studies in Biomechanics. His fields of expertise include biomechanics, nutrition, exercise physiology, strength training, muscular hypertrophy, fat loss and longevity. to Over the last 40 years, he has trained thousands of individuals, including Professional athletes, as well as personally won the State Championships and was finalist at the National Championships at several occasions in both Bodybuilding and Olympic Taekwondo. For more information, you may visit, or reach him at


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