Arginine nitrate

Arginine Nitrate

1. Identity, Chemical Description, and Common Forms

Arginine nitrate — also rendered as L-arginine nitrate or arginine mononitrate — is a salt formed by the combination of the amino acid L-arginine with inorganic nitrate (NO₃⁻). Its common synonyms include arginine nitrate, L-arginine nitrate, and arginine mononitrate; it carries the CAS registry number 223253-05-2, the molecular formula C₆H₁₅N₅O₅, and a molecular weight of approximately 237.21 g/mol. The compound is therefore structurally distinct from free-base L-arginine (CAS 74-79-3, MW 174.20 g/mol) and from other common arginine salts such as arginine alpha-ketoglutarate (AAKG) or arginine silicate.

L-arginine is classified as a basic amino acid due to its side chain containing a guanidinium group, which contributes to its alkaline properties. Its systematic IUPAC name is (S)-2-amino-5-guanidinopentanoic acid. When the amino acid is paired with the nitrate anion to form the salt, both the NOS-dependent pathway (via arginine) and the NOS-independent nitrate–nitrite–NO pathway (via the nitrate moiety) are theoretically available to the body following ingestion, which is the principal pharmacological rationale for the compound's formulation.

Raw arginine is a commonly used supplement for increasing blood flow via nitric oxide production, and arginine has been bound to nitrate specifically to increase bioavailability. Arginine nitrate is marketed commercially in powder, capsule, and tablet forms, and appears in the U.S. NIH Dietary Supplement Label Database as a recognized ingredient in marketed U.S. dietary supplement products.

The compound is commercially available under the trademarked ingredient designation NO3-T® in the sports nutrition industry, appearing primarily in pre-workout and pump-enhancement formulas. L-arginine is often used for its vasodilatory effects, and supplementation with nitrates has more recently become popular for the same reason.

2. Natural Sources and Dietary Context

Arginine nitrate as a discrete chemical entity is not found naturally in foods; it is a synthetic salt produced for supplement or pharmaceutical use. Its two constituent parts, however, are both endogenous and dietary in origin.

L-Arginine in Foods

L-arginine is a semi-essential amino acid that plays a crucial role in various physiological processes. It is classified as semi-essential, meaning that while the body can produce it, certain conditions may require additional intake from dietary sources; it is naturally found in protein-rich foods such as meat, fish, dairy, nuts, and legumes. Because most arginine in the typical American diet is obtained from meat and fish, which provide about 5.5 g daily, vegetarians may be at risk for arginine deficiency.

Dietary Nitrate in Foods

The major sources of dietary nitrate are green leafy vegetables and roots such as lettuce, spinach, rucola, and beetroot. Green leafy vegetables, such as spinach and beetroot, are the main nitrate sources — approximately 80% — in the majority of human diets. Inorganic nitrate is therefore a naturally occurring component of a vegetable-rich diet, and its relevance to human nitric oxide biology has been recognized since the early 2000s.

Endogenous Arginine Synthesis

Internally, around 80% of arginine in the body is produced through protein turnover and 15% is synthesized from citrulline in the urea cycle; most de novo synthesis happens via the intestinal-renal axis, where citrulline is produced by epithelial cells in the small intestine, mainly from ornithine, glutamine, and glutamate. L-arginine is classified as a nonessential amino acid but may be considered essential or semiessential under conditions of stress when the capacity of endogenous arginine synthesis is exceeded, including during periods of growth (childhood, pregnancy) or trauma (liver disease, severe sepsis, wound healing, cancer).

3. Historical and Traditional Context

Arginine nitrate as a combined dietary supplement ingredient is a modern formulation with no traditional or ethnobotanical history of use. The constituent amino acid L-arginine, however, has a well-documented scientific history, and the pharmacological interest in its nitric oxide–generating properties forms the direct intellectual lineage of the current compound.

Discovery of L-Arginine

L-arginine was first identified in extracts of etiolated lupine seedlings by Schultz and Steiger in 1886; it was shown to be a product of protein hydrolysis by Hedin nine years later, and its structure was not proven until 1910 by Sorenson. In its crystallized form, it has a silvery appearance, which inspired Schulze to name it after the Greek word for silver, árgyros. When Krebs and Henseleit discovered the ornithine (urea) cycle in 1932, arginine's role in metabolism and physiology began to be further elucidated.

The Nitric Oxide Connection

By 1980, it was thought that most major mechanisms regulating vascular tone were understood; however, after the discovery that endothelium is involved in mediation of relaxation to acetylcholine, a whole new world opened up, and the new player was identified as nitric oxide (NO), an endothelium-derived relaxing factor. This discovery — ultimately recognized with the 1998 Nobel Prize in Physiology or Medicine — reframed L-arginine's importance: NO is produced from L-arginine and oxygen by enzymatic reactions catalyzed by NOS isoforms, such as endothelial nitric oxide synthase (eNOS).

Clinical and Supplement History of L-Arginine

L-arginine has been evaluated for use in cardiovascular disease because of its antiatherogenic, anti-ischemic, antiplatelet, and antithrombotic properties, and for use in renal disease, diabetes, cystic fibrosis, sickle cell disease, and erectile dysfunction. From the 1990s onward, L-arginine appeared in both intravenous clinical preparations and oral dietary supplements. The development of arginine nitrate as a distinct salt aimed to combine the NOS-dependent NO precursor activity of L-arginine with the NOS-independent nitric oxide generation potential of dietary nitrate in a single molecule.

4. Key Constituents and Mechanisms of Action

Arginine nitrate delivers two pharmacologically active moieties upon ingestion: L-arginine and inorganic nitrate (NO₃⁻). Each moiety has a distinct, well-characterized mechanism by which it contributes to nitric oxide (NO) biology.

4.1 The L-Arginine–NOS–Nitric Oxide Pathway

In the NOS-dependent mechanism, NO is produced from L-arginine and oxygen by enzymatic reactions catalyzed by NOS isoforms, including endothelial nitric oxide synthase (eNOS). L-arginine is a substrate of nitric oxide synthase, which converts it to citrulline and nitric oxide (NO). L-arginine is the precursor of endogenous nitric oxide, which is a potent vasodilator acting via the intracellular second-messenger cGMP.

NO serves as a critical mediator of vascular function, contributing to vasodilation, the regulation of blood flow, and the prevention of thrombosis; as a primary precursor of NO, L-arginine is essential for maintaining endothelial integrity, modulating mitochondrial function, and reducing oxidative damage.

L-arginine plays a vital role in numerous metabolic pathways, such as the synthesis of nitric oxide, the urea cycle, and protein synthesis. Arginine becomes a conditionally essential amino acid during periods of stress; it is important for T-cell functioning, collagen synthesis, and production of growth hormone, prolactin, somatostatin, insulin, and glucagon.

An important limitation of the NOS-dependent pathway should be noted: nitric oxide dietary supplements are extremely popular within the sport and bodybuilding community; most contain L-arginine, for which there is no direct evidence that oral L-arginine increases circulating nitric oxide or blood flow. This limitation is related to first-pass metabolism, NOS saturation under resting conditions, and the "arginine paradox," whereby cells already saturated with arginine do not appear to produce more NO simply by increasing substrate availability.

4.2 The Nitrate–Nitrite–Nitric Oxide (NOS-Independent) Pathway

For decades, the synthesis of NO was attributed solely to the L-arginine-dependent nitric oxide synthase (NOS) enzymes; however, the discovery of the nitrate–nitrite–NO pathway has revealed an alternative, NOS-independent mechanism for NO generation that is particularly significant under hypoxic and acidic conditions characteristic of exercising skeletal muscle.

The pathway proceeds via a sequential reduction process. Ingested nitrate is absorbed in the upper gastrointestinal tract and circulates in the plasma. A fraction is actively taken up by the salivary glands and secreted in saliva. Some of the salivary nitrate — approximately 5–36% — is reduced to nitrite by specific oral commensal bacteria in the mouth, ensuring continuous substrate delivery for oral nitrite generation. The nitrite-enriched saliva is then swallowed and, in the acidic environment of the stomach, nitrite is further reduced to NO and other bioactive nitrogen oxides. For nitrate to become biologically active, it first needs to be reduced to the more reactive nitrite anion; the existence of this in vivo reduction was established by Lundberg and Govoni, who noted a fourfold sustained increase in plasma nitrite in healthy volunteers after nitrate ingestion, an effect that was abolished if subjects avoided swallowing for one hour post-ingestion, confirming the necessity of the enterosalivary circuit.

Along with the canonical L-arginine–NO pathway, NO is also produced from nitrate through the nitrate–nitrite–NO pathway; this is particularly relevant since NO is produced from nitrate — traditionally regarded as an end product of NO oxidation — without the involvement of NO synthases. Results from animal research show that dietary nitrate fuels a nitrate–nitrite–NO pathway that can partly compensate for disturbances in endogenous NO generation from eNOS.

As clinical research confirms, the reduction of inorganic nitrate and nitrite in vivo results in NO production; not only does nitrate generate NO, but nitrate and nitrite are inert end-products of NO oxidation — that is, nitrate converts into NO, and once oxidized, NO is recycled back into nitrate, which then has the potential to convert into NO once again in a repeating cycle.

4.3 Dual-Pathway Rationale for Arginine Nitrate

The commercial and scientific logic behind formulating arginine nitrate as a compound salt is that it makes both NO-generating mechanisms available simultaneously from a single molecule. The nitrate moiety provides a substrate for the NOS-independent pathway — which is particularly active under low-oxygen, acidic conditions typical of intense muscular exercise — while the arginine moiety provides substrate for eNOS-mediated NO production at rest and under normal tissue oxygenation. Whether this dual delivery results in meaningfully additive or synergistic NO production compared to either component alone has not been rigorously established in long-term human trials.

A secondary role concerns the role of nitric oxide in insulin signaling: the production of nitric oxide facilitates insulin-mediated glucose uptake by promoting blood flow. Additionally, L-arginine induces insulin release by a nitric oxide-dependent mechanism.

5. Scientific Evidence by Area of Use

5.1 Hemodynamics and Exercise-Induced Vasodilation

The most directly relevant human clinical data on arginine nitrate specifically — as opposed to either L-arginine or inorganic nitrate individually — comes from a 2015 study published in the Journal of the International Society of Sports Nutrition.

In this study, increasing blood flow to skeletal muscle during exercise was the primary focus; raw arginine is commonly used for increasing blood flow via nitric oxide production, and arginine has been bound to nitrate to increase bioavailability; the purpose was to determine the acute hemodynamic effects of raw arginine (RA), arginine peptide (AP), arginine nitrate (AN), and placebo (PLA) following resistance exercise in healthy, recreationally-active men at doses commonly used in the marketplace.

In a double-blind, crossover, placebo-controlled design, 11 recreationally-active males (28.2 ± 5.0 y, 182.4 ± 5.7 cm, 87.1 ± 10.3 kg) consumed either 1.87 g of RA, 3.07 g of AP (arginine content 1.87 g), 2.55 g of AN (arginine content 1.87 g), or a flavor-matched, visually identical placebo (PLA), and performed 3 sets of 15 arm curls at 30 and 120 minutes post-supplementation. Vessel diameter of the brachial artery and blood flow volume were measured via Doppler ultrasound at 0, 3, and 6 minutes post-exercise, corresponding to 30, 33, 36, 120, 123, and 126 minutes post-supplementation.

A significant group × time interaction was observed for raw arginine compared to placebo, with post-hoc analyses revealing that raw arginine increased vessel diameter versus placebo at 30 minutes post-exercise; significantly greater percent change values were observed for vessel diameter when comparing raw arginine and placebo at 30 minutes versus the active control. Though raw arginine may significantly increase vessel diameter compared to placebo at 30 minutes post-exercise, arginine peptide induced significantly higher percent change values for blood flow volume compared to raw arginine, placebo, and arginine nitrate at specific time points, and therefore may be the best option for increased blood flow.

Limitations: This was a single acute study conducted in 11 healthy young males, sponsored in part by the International Society of Sports Nutrition. The sample size was small, effects were measured acutely only, and data for arginine nitrate were not distinguished from the other arms as superior. The study was published as a conference proceedings abstract rather than a full peer-reviewed article, limiting its weight of evidence.

5.2 Multi-Ingredient Formulations Containing Arginine Nitrate

A companion study from the same group aimed to determine the acute hemodynamic effects of a multi-ingredient performance supplement (MIPS) containing arginine and nitrates as compared to placebo following resistance exercise; in a randomized double-blind, crossover, placebo-controlled design, 11 recreationally-active males ingested either one serving (14.5 g) of a MIPS or a flavor-matched, visually identical placebo, and performed 3 sets of 15 arm curls at 30 and 120 minutes post-supplementation. Acute supplementation with a multi-ingredient performance supplement containing arginine and nitrates may increase vasodilation synergistically with resistance exercise 30 minutes post-ingestion. However, because this was a multi-ingredient formulation, no conclusions can be drawn specifically about arginine nitrate's contribution.

5.3 L-Arginine Alone: Exercise Performance Evidence

Because arginine nitrate's arginine moiety is the same as free L-arginine, the broader clinical literature on L-arginine supplementation is directly relevant to understanding the compound's expected properties. This evidence base is mixed.

Nitric oxide-related ergogenic aids such as arginine have shown positive impacts on sport performance through several physiological and metabolic mechanisms; however, research results have been controversial, and the great differences regarding required metabolic pathways between aerobic and anaerobic sport disciplines could be reasons for inconsistency.

One study found no benefit of L-arginine supplementation on exercise performance: there was no significant difference between arginine and placebo trials in plasma nitrate and nitrite, lactate and ammonia concentrations, or peak and average power in intermittent exercise; short-term arginine supplementation had no effect on nitric oxide production, lactate and ammonia metabolism, and performance in intermittent anaerobic exercise in well-trained male athletes.

In a randomized, double-blind, placebo-controlled crossover trial of 30 healthy physically active adults (15 male, 15 female): the purpose was to examine the acute endothelial, cardiovascular, and performance responses to L-arginine intake by assessing flow-mediated dilation and various indicators before and after resistance exercise; participants completed five sets of elbow extension-flexion exercise after consumption of either 3 g L-arginine or 3 g of placebo; there was a significant decline in post-exercise elbow extension and flexion peak torque, and FMD response after exercise was approximately 5.8% less than before resistance exercise in both groups pooled.

A separate study found that dietary supplements containing L-arginine have been marketed for increasing vasodilation and blood and oxygen supply to exercising muscle, and one controlled study evaluated the acute effect of L-arginine supplementation on indicators of NO production — nitrite plus nitrate — in healthy subjects. The preponderance of evidence from multiple trials suggests that standalone acute L-arginine supplementation does not reliably elevate circulating markers of NO production in healthy, well-nourished individuals, a finding attributed to NOS saturation and degradation of L-arginine before it reaches target tissues.

5.4 Dietary Nitrate (from the Nitrate Moiety): Evidence for Exercise and Cardiovascular Outcomes

The nitrate moiety of arginine nitrate draws on a well-established body of research investigating inorganic nitrate — primarily from beetroot juice — in exercise and cardiovascular contexts.

In older adults with a mean age of 71 years, acute nitrate supplementation increases plasma nitrate, nitrite, and exhaled NO while improving knee extensor power and angular velocity, paralleling similar observations in young adults; in this age group, nitrate increases both evoked muscle force production and excitation–contraction coupling of skeletal muscle. The molecular mechanisms include an increase of NO bioavailability and the downstream phosphorylation of myofibrillar proteins; nitrate has also been shown to promote muscle force production in vitro by increasing the expression of calcium-handling proteins, thereby improving intracellular calcium handling.

Animal and preclinical data further support the nitrate moiety's cardiovascular relevance: it was first shown in rat heart that nitrite infusion could reduce infarct size, an effect that was negated by a nitric oxide scavenger; nitrite administration protected equally against ischemia in eNOS knockout mice, confirming that protective effects were conferred in an NO-dependent but NOS-independent manner; additional studies also showed a benefit of oral nitrate supplementation in reducing infarct size, reinforcing the clinical significance of the reduction of dietary nitrate to nitrite.

Caution in translation: Most of this research specifically concerns sodium nitrate or dietary nitrate from vegetables at dosages supplying several hundred milligrams of nitrate. The nitrate content of an arginine nitrate dose supplying 1.87 g of arginine (approximately 2.55 g of arginine nitrate) is quantitatively much smaller than the amounts tested in most beetroot or sodium nitrate exercise studies. The extent to which the nitrate moiety in arginine nitrate doses used in supplements reaches the threshold for significant NOS-independent NO generation has not been independently verified.

5.5 Cardiovascular Disease: L-Arginine and Blood Flow

L-arginine is the precursor of endogenous NO, which is a potent vasodilator acting via the intracellular second-messenger cGMP; in healthy humans, L-arginine induces peripheral vasodilation and inhibits platelet aggregation due to increased NO production.

In patients with precapillary pulmonary hypertension, one clinical trial found that a one-week supplementation of L-arginine resulted in a slight increase in peak VO₂ (from 831 ± 88 to 896 ± 92 mL/min, p < 0.05) and a significant decrease in the VE–VCO₂ slope (from 43 ± 4 to 37 ± 3, p < 0.05) without significant systemic hypotension; hemodynamics and exercise capacity remained unchanged during placebo administration; these results suggest that oral supplementation of L-arginine may have beneficial effects on hemodynamics and exercise capacity in patients with precapillary pulmonary hypertension.

L-arginine has been evaluated for use in cardiovascular disease because of its antiatherogenic, anti-ischemic, antiplatelet, and antithrombotic properties, and for use in renal disease, diabetes, cystic fibrosis, sickle cell disease, and erectile dysfunction; its immunostimulatory effects and potential benefits in ophthalmic conditions and preeclampsia have also been evaluated.

5.6 Immune Function, Wound Healing, and Critical Illness

Arginine becomes a conditionally essential amino acid during periods of stress, including burns and trauma; it is important for T-cell functioning, collagen synthesis, and production of growth hormone, prolactin, somatostatin, insulin, and glucagon. Following trauma and surgery, there is a drop in arginine synthesis; multiple studies have demonstrated a decrease in postoperative infections and hospital length of stay in patients when using an arginine-containing formula in conjunction with other immune-enhancing ingredients, particularly omega-3 fatty acids. These findings relate to L-arginine and not to arginine nitrate specifically.

6. Body Systems and Health Areas

• Cardiovascular system: NO contributes to vasodilation, the regulation of blood flow, and the prevention of thrombosis. Both the arginine and nitrate components of arginine nitrate are relevant to NO-mediated vascular function.
• Skeletal muscle and exercise performance: NO is a pleiotropic signaling molecule fundamentally involved in regulating skeletal muscle physiology, including blood flow, contractility, and metabolism.
• Endocrine / metabolic: The production of nitric oxide facilitates insulin-mediated glucose uptake by promoting blood flow. Nitrate has important pathophysiological functions in diseases such as cardiovascular diseases, gastrointestinal diseases, diabetes, and metabolic diseases via nitrate-reducing bacteria.
• Immune system: Arginine is important for T-cell functioning and collagen synthesis.
• Nitrogen metabolism / urea cycle: L-arginine is important for the urea cycle, helping to eliminate ammonia from the body.
• Oral microbiome and enterosalivary axis: The enterosalivary nitrate–nitrite–NO pathway represents a symbiosis between oral nitrate-reducing bacteria and their human hosts in which the bacteria provide nitrite and nitric oxide from nitrate reduction.

7. Dosage Forms and Dosages Reported in Studies

Arginine nitrate is available commercially in powder, tablet, and capsule forms.

In the principal published human study specifically investigating arginine nitrate, 2.55 g of arginine nitrate (delivering 1.87 g of arginine content) was used as the test dose, administered acutely in a crossover design.

For the broader L-arginine literature from which safety and dosing context is drawn: L-arginine has been studied for a variety of conditions using various dosages and treatment durations; current daily dosage trends range from 6 to 30 g orally in 3 divided doses; oral and intravenous formulations have been the most commonly studied.

In the VINTAGE MI post-myocardial infarction trial, the dose was structured as a goal dose of 3 g, three times daily (9 g/day total).

In a pulmonary hypertension study, a 1-week supplementation of L-arginine resulted in modest improvements in VO₂ and ventilatory efficiency. The exact dose used in that study is stated in the abstract as achieving plasma changes in the cited outcomes.

For GI tolerability reference: single doses of 3–6 g rarely provoked side effects; most side effects of arginine occurred at single doses of greater than 9 g in adults (greater than 140 mg/kg), often as part of a daily regimen of approximately greater than 30 g/day.

8. Safety Considerations and Drug Interactions

The safety profile of arginine nitrate has not been independently evaluated in long-term human studies. The available safety data derive from the extensive clinical literature on L-arginine supplementation and from the well-characterized pharmacology of inorganic nitrate.

8.1 Gastrointestinal Adverse Effects

Gastrointestinal toxicity has been reviewed with respect to the intestinal physiology of arginine; the human intestinal dibasic amino acid transport system has high affinity and low capacity; L-arginine (but not lysine, ornithine, or D-arginine) induces water and electrolyte secretion mediated by NO, which acts as an absorbagogue at low levels and as a secretagogue at high levels; there are reports of diarrhea following oral administration of arginine. Most side effects occurred at single doses of greater than 9 g in adults; adverse effects seemed dependent on the dosage regimen and disappeared if divided doses were ingested.

8.2 Post-Myocardial Infarction: A Critical Safety Signal

The most significant safety signal in the L-arginine literature involves its use in patients who have recently experienced a myocardial infarction. The placebo-controlled VINTAGE MI trial, published in the January 4, 2006 issue of JAMA, found no effect of L-arginine therapy on vascular stiffness or left ventricular function in post-MI patients and suggested that it may actually worsen clinical outcome in older patients with diffuse atherosclerosis. Six participants (8.6%) in the L-arginine group died during the 6-month study period versus none in the placebo group (P = .01); because of the safety concerns, the data and safety monitoring committee closed enrollment; L-arginine, when added to standard postinfarction therapies, does not improve vascular stiffness measurements or ejection fraction and may be associated with higher postinfarction mortality. The authors concluded that L-arginine therapy should not be given to patients following a myocardial infarction.

L-arginine is thought to have benefits for patients with hypertension, angina, heart failure, and sexual dysfunction; however, in animal studies, increasing nitric oxide levels has been shown to worsen outcomes in severe atherosclerosis, and in older patients with possible more severe atherosclerosis, the increased mortality was observed. This safety concern, while generated in studies of free L-arginine, is pharmacologically relevant to any supplement delivering L-arginine, including arginine nitrate.

8.3 Drug Interactions

L-arginine may interact with nitrate medications, such as nitroglycerin, isosorbide dinitrate, or isosorbide mononitrate (medicines used to prevent or treat chest pain), and with phosphodiesterase-5 (PDE5) inhibitors such as sildenafil, tadalafil, and vardenafil (medicines used for erectile dysfunction or pulmonary arterial hypertension); the interactions between L-arginine and these medicines are not fully understood. Because arginine nitrate itself contains a nitrate anion, the additive hypotensive risk with nitrate-based cardiac medications is of direct concern. L-arginine may interact with certain medications that lower blood pressure.

8.4 Electrolyte Concerns

There is some evidence to suggest that arginine supplementation may affect electrolyte balance, particularly potassium levels; high doses of arginine can lead to hyperkalemia, a condition characterized by elevated potassium levels in the blood. IV preparations containing L-arginine hydrochloride have a high chloride content that may increase the risk for metabolic acidosis; this concern is specific to the hydrochloride salt and may not apply to the nitrate salt.

8.5 Herpes Viral Infections

Individuals with herpes infections should exercise caution when taking arginine, as it can potentially exacerbate outbreaks; arginine serves as a building block for the herpes virus, which may lead to increased frequency or severity of outbreaks in susceptible individuals.

8.6 Tolerability at Lower Doses

In clinical trials, L-arginine has been used safely with minor side effects for up to three months; possible side effects include abdominal pain and bloating, diarrhea, and gout; it may also cause a worsening of breathing in people with asthma.

8.7 Safety of the Nitrate Moiety at Supplement Doses

A U.S. patent discloses a method of safely administering nitrates in reduced-side-effect form by combining an inorganic nitrate with an amino acid compound to produce an amino acid nitrate salt, describing that this combining reduces the side effects or toxicity of the inorganic nitrate, including nausea, gastric distress, gastric ulcer, diarrhea, abdominal pain, and methemoglobinemia. This provides the formal regulatory and intellectual property rationale for the arginine nitrate formulation in the context of gastrointestinal tolerability.

9. Limitations of the Current Evidence Base

It is important to note that, as of the available literature, arginine nitrate as a specific compound has been evaluated in very limited human clinical research. The principal published study (Falcone et al., 2015) was a small, acute, conference-proceedings study. The large body of evidence on L-arginine and on dietary nitrate was generated with different compounds, different doses, and in different populations. Extrapolating those findings directly to arginine nitrate's specific performance in supplement doses requires caution. Long-term randomized controlled trials specifically examining arginine nitrate supplementation — its pharmacokinetics, NO bioavailability relative to either component alone, and its effects on validated performance or health endpoints — have not been published in the peer-reviewed literature as of the time of this article.

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