N0 Extreme is unique in the fact that it uses Arginine-AKG, Citrulline-Malate, and Ornithine-AKG to increase nitric oxide via the inducible Nitric Oxide Synthase (iNOS) enzyme at different time intervals. N0 Extreme also utilizes the endothelial NOS/constitutive NOS (eNOS/cNOS) enzyme in NO production via the use of Magnesium Tashinoate B (MTB). The amino acid derivative norvaline also helps prevent the breakdown of the body’s endogenous levels of Arginine (the direct precursor of NO). One of the newest NO-boosting compounds to enter the nutraceutical market, N-carbamylglutamate, is also infused into N0 Extreme, along with Cellucor’s first ever-designed Arginine-Picamilon compound. This combination of NO-enhancing agents induces unparalleled vascularity for strength and endurance.
Activating iNOS is accomplished via Arginine through the NO Cycle (i.e., Arginine -> Citrulline and NO OR -> Ornithine -> Citrulline -> Arginosuccinate OR Citrulline -> Arginine and diatomic oxygen -> Agmatine OR recirculation of Arginine through the cycle).
Arginine is a requirement for all nitric oxide production via the iNOS enzyme. The Arginine metabolite, Agmatine, also has vasodilating effects, but can inhibit iNOS as well. Using Citrulline and Ornithine provide additional Arginine precursors that become nitric oxide, and create a time-released effect due to the different biological conversions that must take place.
The Malate and Alpha Ketoglutarate (AKG) moieties on these particular NO precursors in N0 Extreme have a two-fold effect. Both Malate and AKG are particular intermediates in the Tri-Carboxylic Acid (TCA) cycle. This cycle occurs in the mitochondria of all cells of the body and is responsible for the metabolism of nutrients from food (protein, carbohydrates, and fats) into usable energy in the form of ATP. The bonds on theses NO precursors enhance ATP production within the cell; since both Malate and AKG are intermediates in the TCA cycle, they are recognized and taken up quickly by the cell. The NO precursors that are complexed with these TCA intermediates become uncoupled in the mitochondria, and are released back into the cell to participate in biological processes.
N0 Extreme also activates the cNOS enzyme through MTB. The activation of cNOS occurs commonly when calcium is abundant and produces NO through its metabolites, nitrite and nitrate. Nitrates are found typically in most plant matter that is consumed in the diet, and the use of synthetic nitrates has reached pharmaceutical status in blood pressure medications.
MTB is the active component of S. miltiorrhiza, the common Chinese Danshen. Clinically, MTB has been shown to increase the release of NO metabolites from endothelial cells. When these nitric oxide metabolites are released into the bloodstream, the cNOS enzymes quickly recognize and metabolize them into nitric oxide.
The next step that N0 Extreme takes in maximizing nitric oxide production is to limit the main enzyme, Arginase, which is responsible for catabolizing overly abundant Arginine. The amino acid derivative, Norvaline, acts as a competitive inhibitor of Arginase while Arginine is converted into NO.
The use of N-carbamylglutamate (NCG) and Arginine-Picamilon is where N0 Extreme’s NO-boosting power goes above and beyond any other NO product that is sold today.
NCG is an amino acid derivative that has been discovered recently to activate the release of stored Arginine from endothelial cells into the bloodstream. Additionally, NCG has been shown to increase protein synthesis and the release of Somatotropin (human growth hormone) into the bloodstream. The results of clinical trials with NCG show that it is very safe, even in large doses, and has very profound effects on muscle growth and protein synthesis.
Arginine-Picamilon is a new innovative compound from Cellucor that increases blood flow to the brain. Picamilon is bound to Gamma-amino butyric acid (GABA) via niacin. N0 Extreme’s Arginine-Picamilon works by causing vasodilation in the brain and an abundance of cerebral blood flow. The GABA moiety binds the GABA receptor, which is located on the same cells as those that secrete somatotropin. The activation of the GABA receptor also potentiates the secretion of Somatotropin, which enhances growth and protein synthesis.
When N0 Extreme stimulates NO, the blood vessels expand in a process known as vasodilation, which enhances the efficiency at which blood, essential nutrients, amino acids, and vitamins are delivered to muscle cells, essentially stimulating their growth and proliferation.
For many decades, the use of branched-chain amino acids, BCAAs, have caused great gains in anabolic muscle growth. N0 Extreme delivers these essential amino acids to help harness the anabolic state.
The reason why branched-chain amino acids are so necessary is because of their role in protein synthesis. BCAAs are the rate-limiting factors in protein synthesis because of their function in creating hydrogen bonds within proteins that are responsible for the variations in protein structure.
The provision of these amino acids by N0 Extreme allows for constitutive protein synthesis in the body.
N0 Extreme also uses Beta-Alanine and Histidine to form the dipeptide Carnosine and increase cellular ATP levels very rapidly. Carnosine is known to decrease endogenous pH levels by decreasing hydrogen ion concentration. This effect increases muscular endurance and prevents lactic acid build-up. ?eta-Alanine supplementation with Histidine yields effects very similar to creatine with respect to ATP synthesis without causing an increase in intra-muscular water levels.
N0 Extreme increases pre-workout energy levels by providing certain compounds that have never been seen on the supplement market previously. N0 Extreme takes an athlete to the “next level” of fitness by harnessing much more energy than it would in a normal state, where the gains go from impressive to extraordinary.
N0 Extreme addresses the energetic stimulation concept from three different angles: ATP synthesis via methylxanthines, monoamine secretion via phenethylamines, and enhancement of the mind-muscle connection.
Methylxanthines are a class of compounds that encompass many simple stimulants with effects on endogenous ATP levels. N0 Extreme utilizes two particular methylxanthines, Caffeine and Theobromine, to inhibit cyclic adenosine monophosphate (cAMP) phosphodiesterase. This inhibition leads to a build-up of cAMP in cells; cAMP becomes phosphorylated and subsequently causes a sudden surge in ATP levels. In addition, methylxanthines can cross the blood-brain barrier where they can bind adenosine receptors and cause a large release of monoamines.
N0 Extreme takes another huge leap in the pre-workout energy field using Methyltyramine and Methylsynephrine, compounds in a class known as phenethylamines. Phenethylamines induce psychoactive responses, which then lead to a physiological response. An example would be the exciting effects felt after secretion of a large amount of adrenaline, one of the body’s most abundant phenethylamines as well as a monoamine. The main monoamines in the body are Adrenaline (Epinephrine), Noradrenaline (Norepinephrine), Serotonin, and dopamine, all of which have specific effects.
Methyltyramine specifically increases the secretion of norepinephrine and results in psychological feelings of very intense focus, determination, and goal-oriented behavior. This compound is also a ß-adrenergic receptor agonist, discussed below.
Methylsynephrine is more specific for Adrenaline and is similar to Ephedrine. Coincidentally, Methylsynephrine and Ephedrine differ only by one chemical substituent, a hydroxyl group, on its phenyl ring.
Both Methyltyramine and Methylsynephrine are ß-adrenergic receptor agonists. When these receptors are activated, a very interesting cascade of events ensues. The body begins a series of “fight or flight” responses, including increased heart rate, increased muscle blood flow, increased muscular thermogenesis, increased fat metabolism, and increased ATP levels. Metabolically, the stimulation of the ß-adrenergic receptors has many benefits such as increased muscle growth, decreased body fat, and overall feelings of wakefulness and clarity of the mind.
In combination with the effects of the Methylxanthines and phenethylamines, N0 Extreme takes it one step further by the use of Vinpocetine. Vinpocetine is a very unique compound that causes vasodilation of vessels in the brain and muscles simultaneously. Many clinical trials have shown that it also increases mental and cognitive functions and mind-muscle coordination.
Like many other Cellucor products, N0 Extreme regulates blood sugar by enhancing insulin sensitivity. Through N0 Extreme’s use of Oxovanadium, the body’s response to blood sugar results in the formation of more intra-muscular glycogen than the storage of body fat. Oxovanadium, in very small dosages, mimics insulin’s activity in muscle by converting excess glucose into glycogen, a storage form of sugar within muscles, as opposed to the storage of excess sugar as fat. The modulatory effects of Oxovanadium result in a drastic increase in muscular power and endurance.