IngredientesNitrous Malate™ is a trademarked designation applied to diarginine malate (also written di-arginine malate, di-L-arginine malate, or diarginine L-malate). Diarginine malate is a compound that combines two L-arginine molecules with malic acid. It belongs to a class of amino acid–organic acid salt complexes that have become common in sports-nutrition formulation, following the same structural template as related compounds such as dicreatine malate and dicitrulline malate.
The compound is systematically named arginine – 2-hydroxysuccinic acid (2:1) under IUPAC convention, also appearing as arginine, compd. with 2-hydroxybutanedioic acid (2:1); the commercial synonym registered in chemical databases is Diarginine Malate. Its molecular formula is C17H35N9O6 with a molecular weight of approximately 461.52 g/mol. A second molecular formula, C16H34N8O9, is also recorded in chemical structure databases, reflecting variation in the stoichiometric accounting of the salt bond, particularly when the malate anion is expressed as malic acid (2-hydroxysuccinic acid) rather than its deprotonated form.
The compound is catalogued under multiple synonyms including: arginine malate, di arginine malate, di-arginine malate, (di-L-arginine)-L-malate, di-L-arginine malate, L-arginine DL malate, L-arginine malate, and nitrous malate diarginine malate. The NIH Dietary Supplement Label Database (DSLD) lists DiArginine Malate as a recognised ingredient in products marketed in the United States.
In a US patent (USPTO 8,642,095) for a dietary composition, diarginine malate is characterised as a vasodilator ingredient and is described as constituting 10–30 percent by weight of the total admixture. This patent framing illustrates the ingredient's primary commercial identity as a nitric-oxide–supporting compound intended for pre-workout or performance contexts.
Diarginine malate is an ionic complex of two distinct biologically active molecules — L-arginine and L-malic acid — which are non-covalently associated as an arginine salt of malate.
L-Arginine: L-arginine is classified as a semi-essential amino acid that plays a central role in numerous physiological processes, most notably as a precursor for nitric oxide (NO) synthesis. L-arginine is a conditionally essential amino acid whose deficiency has been reported to be related to a variety of inflammatory and oxidative processes leading to metabolic disorders and cardiovascular diseases. Besides its availability from dietary intakes, L-arginine is provided from endogenous pathways, including protein turnover and de novo synthesis from citrulline in the urea cycle.
L-Malic Acid (L-Malate): Malic acid exists in three isomeric forms: D-, L- and DL-malic acid; in nature, L-malic acid is the predominant form and is ubiquitously present in animal, plant, and microbial cells. Malic acid is an intermediate in the tricarboxylic acid (TCA) cycle and participates in mitochondrial energy metabolism.
L-arginine is naturally concentrated in protein-rich foods. L-arginine is found in many protein-containing foods, especially animal products and nuts, with a typical dietary intake of 4–5 grams per day. L-malic acid occurs naturally in fruits, with particularly high concentrations in apples and other tart fruits, and is a ubiquitous metabolic intermediate in all aerobic organisms. L-malic acid is ubiquitously present in animal, plant, and microbial cells.
In commerce, diarginine malate / Nitrous Malate™ is supplied primarily as a white crystalline or fine powder for incorporation into dietary supplements. It appears most frequently in pre-workout and sports-nutrition formulations — including powdered drink mixes, capsules, and tablets. This compound has found its place in modern nutritional supplements, especially in sports nutrition, where it is appreciated for reducing exercise-induced fatigue and enhancing performance. In herbal combinations, arginine malate is often included alongside adaptogens such as ginseng, rhodiola, or ashwagandha, with such blends aiming to maximise energy, endurance, and recovery.
Diarginine malate as a defined, isolated chemical entity is a product of modern nutritional science with no documented traditional use in any historical pharmacopoeia or ethnobotanical record. However, the two constituent moieties — L-arginine and malic acid — each carry historical significance in food and medicine.
While the use of pure arginine malate is a relatively modern development, both of its constituents have long-standing histories in traditional and medicinal applications. L-arginine has roots in traditional remedies, particularly for its role in supporting cardiovascular health and enhancing vitality. Ancient herbalists valued arginine-rich foods, such as nuts and seeds, for promoting circulation and male fertility.
L-malic acid, as the principal acid of apples and many stone fruits, has been a component of food-based remedies across cultures for millennia, though historical practitioners did not isolate or characterise it chemically. The isolation and naming of malic acid is attributed to Carl Wilhelm Scheele in 1785, who extracted it from apple juice.
In modern times, L-arginine has been extensively studied for its ability to increase nitric oxide production, thereby supporting healthy blood flow, reducing fatigue, and aiding muscle recovery. The specific formulation of two arginine molecules salt-bound to one malate anion is a commercial and formulation innovation of the late twentieth and early twenty-first centuries, designed to deliver both substrates simultaneously in a single, stable compound.
L-arginine is involved in production of nitric oxide (NO), an important signalling molecule in biological pathways, as the substrate of the nitric oxide synthase (NOS) enzyme family. Vascular nitric oxide (NO) is released from endothelium and has a direct vasodilator effect on healthy human arterial tissues; L-arginine is the main precursor of nitric oxide released from vascular endothelium via endothelial nitric oxide synthase (eNOS).
The L-arginine/NO pathway is involved in many physiological processes, and any changes in this pathway can be related to the development of diseases. Nitric oxide produced from L-arginine has potent antioxidant and anti-inflammatory properties. As a primary precursor of NO, L-arginine is essential for maintaining endothelial integrity, modulating mitochondrial function, and reducing oxidative damage.
Arginine synthesises nitric oxide by nitric oxide synthase, and nitric oxide plays a vital role as an intercellular messenger and neurotransmitter in the cardiovascular system and nervous system, including promoting vasodilation, inhibiting platelet aggregation, and inhibiting smooth muscle cell proliferation.
Beyond NO synthesis, L-arginine participates in the urea cycle, where it is cleaved by arginase into ornithine and urea. The products of arginase include L-ornithine, which is further cleaved to polyamines by ornithine decarboxylase, and to L-proline by ornithine aminotransferase, and urea; these compounds may exert negative effects on glucose metabolism. This bifurcation of arginine metabolism — toward either NO production or polyamine/urea synthesis — is a key determinant of arginine's net physiological effects and is context- and dose-dependent.
Some experts suggest that taking arginine in supplement form enhances exercise and athletic performance in several ways, primarily because some arginine is converted to nitric oxide, a potent vasodilator that can increase blood flow and the delivery of oxygen and nutrients to skeletal muscle.
L-malate, a tricarboxylic acid cycle (TCA) intermediate, plays an important role in transporting NADH from the cytosol to mitochondria for energy production and may be involved in beneficial effects on improving physical stamina. This dicarboxylic acid plays pivotal roles in mitochondrial energy production, redox homeostasis maintenance, anti-inflammatory responses, and fatty acid biosynthesis.
Malic acid is widely known as an intermediate of the TCA cycle and plays an important role in transporting NADH from the cytosol to mitochondria for energy production. Malic acid is a TCA cycle intermediate and an important part of the malate–aspartate shuttle, placing it at the hub of energy metabolism.
The activity of malate dehydrogenase (MDH), an essential enzyme for the conversion of malic acid to oxaloacetate, is typically used as a marker of skeletal muscle oxidative capacity. L-malic acid, a crucial TCA cycle intermediate and gut metabolite, is now recognised as a multifunctional signalling molecule intricately involved in energy metabolism, redox balance, cellular signalling, and host-microbiota crosstalk.
Recent studies have demonstrated that L-malic acid is transported into cells through monocarboxylate transporters (MCTs). Malic acid supplements can promote energy substrates and regulate the level of energy metabolism, improve cardiac function, alleviate sports fatigue, and promote regeneration.
When combined as arginine malate, these ingredients are theorised to offer synergistic effects, promoting energy production, muscular endurance, and cardiovascular function. The rationale is that the arginine moiety provides a substrate for NO-mediated vasodilation and improved nutrient delivery, while the malate moiety replenishes TCA cycle intermediates and facilitates the removal of lactate and ammonia during high-intensity exercise. This dual mechanism closely parallels the rationale applied to the structurally analogous compound citrulline malate, which has a considerably larger body of peer-reviewed evidence. As a nitric oxide enhancer, citrulline malate has been touted as a potential ergogenic aid to both resistance and high-intensity exercise performance; the mechanism has been associated with enhanced blood flow to active musculature, although it might be more far-reaching as ammonia homeostasis could be improved or ATP production could be increased via greater availability of malate.
It is important to emphasise that no peer-reviewed clinical trial has studied diarginine malate as a discrete compound. All available clinical evidence derives from studies of L-arginine (in various salt or free-base forms) or of malic acid / malate, as separate entities.
Background and rationale: Dietary supplements containing L-arginine have been marketed with the purpose of increasing vasodilation, and thus blood and oxygen supply to the exercising muscle. The use of L-arginine supplements has been shown to draw considerable attention regarding enhancement of cardiovascular health and athletic performance, and over the past decade arginine supplements have received considerable attention from researchers in the field of exercise nutrition, who have investigated their potential effects on haemodynamic function, endothelial function, aerobic and anaerobic capacity, strength, power, and endurance.
Evidence — healthy, trained athletes: The evidence for L-arginine as an ergogenic aid in healthy, well-trained individuals is weak and inconsistent. Clinical data do not support the use of L-arginine as an ergogenic aid for strength performance, at least in the context of acute use immediately before resistance exercise. Studies evaluating the acute effect of L-arginine supplementation on indicators of NO production (nitrite + nitrate, NOx) in healthy subjects have not consistently demonstrated significant increases. While there is a scientific basis for the use of arginine-based supplements in exercise aids, and some studies suggest a modest benefit in specific populations, the overall evidence for significant performance enhancement in healthy, trained athletes is weak.
Evidence — overweight or less-trained individuals: Some clinical evidence suggests greater responsiveness in deconditioned or overweight populations. A randomised placebo-controlled trial found that supplementation with 6 g of L-arginine significantly reduced cardiorespiratory responses during high-intensity interval exercise (HIIE) in overweight men. Measurements of VO₂, ventilation (VE), heart rate, and VE/VCO₂ were obtained; supplementation with L-arginine significantly decreased cardiorespiratory responses during HIIE, with VE reduced from 80.9 ± 4.3 L/min to 74.6 ± 3.5 L/min (p < 0.05).
Evidence — elderly athletes: Nitric oxide has been implicated in improving exercise capacity through vascular smooth muscle relaxation in both coronary and skeletal muscle arteries, and antioxidants may prevent nitric oxide inactivation by oxygen free radicals; one purpose of combining arginine with antioxidants was to investigate effects on exercise performance in elderly male cyclists.
Combined arginine and citrulline malate: One randomised, double-blind, placebo-controlled trial investigated the effects of combined L-arginine and citrulline-malate supplementation on aerobic, anaerobic, and high-intensity interval training in healthy, trained men; both compounds are marketed for potential ergogenic effects, with arginine serving as a precursor to nitric oxide supporting vasodilation; citrulline may enhance and prolong arginine availability, amplifying NO-mediated vasodilation; the trial involved 46 healthy trained men aged 24.8 ± 5.0 years consuming 0.15 g/kg bodyweight of arginine and 0.1 g/kg bodyweight of citrulline malate prior to exercise.
Malate component — animal and preliminary human data: Research has shown that cyclists supplied with malate plus oligosaccharide solution performed cycling to exhaustion for a longer time, with the solution having a good effect on maintaining higher blood glucose concentration during exercise, increasing blood lactate removal rate, and postponing the onset of fatigue. These findings were in a specific combined solution and are not directly applicable to diarginine malate in isolation.
Overall strength of evidence for exercise use: Preliminary and mixed. Most positive findings come from non-trained or clinical populations, or from combined formulations. Supplementation with L-arginine may increase aerobic and anaerobic performance in healthy adults, especially in untrained individuals; however, other studies found no effects of L-arginine supplementation on human performance.
Mechanism: In acute human studies, oral supplementation with L-arginine results in the improvement of endothelium-dependent forearm vasodilation in subjects with pre-existing hyperlipidaemia. The mechanisms by which L-arginine enhances NO production, improves vascular elasticity, and alleviates endothelial dysfunction caused by reduced NO bioavailability have been the subject of investigation.
Blood pressure — meta-analytic evidence: A systematic review and dose-response meta-analysis of randomised clinical trials found clear evidence of blood-pressure reduction with L-arginine supplementation. The pooled analysis demonstrated significant decreases in systolic blood pressure (SBP; weighted mean difference = −6.40 mmHg; 95% CI: −8.74, −4.05; P < 0.001) and diastolic blood pressure (DBP; WMD = −2.64 mmHg; 95% CI: −3.94, −1.40; P < 0.001) after L-arginine supplementation. Subgroup analysis showed significant reductions in SBP and DBP regardless of baseline BP category (normotensive, hypertensive), study duration, sex, health status, and body mass index. However, no significant changes were observed with dosages greater than 9 g/day, trial duration greater than 24 days, or in obese individuals; and L-arginine supplementation appears to decrease DBP more effectively in females than in males.
In the nonlinear dose-response analysis, the effective dosage of L-arginine supplementation was detected to be ≥4 g/day for systolic blood pressure (P = 0.034), independent of trial duration.
Strength of evidence for blood pressure: Moderate. Multiple RCTs exist and pooled analyses show statistically significant reductions, though effect sizes are modest and significant heterogeneity exists across trials. Current meta-analyses for L-arginine interventions in blood pressure have identified significant heterogeneity, and inconsistencies in study design pose a challenge for systematic reviews and meta-analyses to accurately assess effect size.
Nitric oxide is the main vasoactive neurotransmitter of penile erection, controlling smooth muscle relaxation; L-arginine is the precursor of NO, a neurotransmitter necessary for relaxation of the penile muscles.
A significant multicentre, double-blind, randomised, placebo-controlled clinical trial addressed the effects of high-dose L-arginine on vasculogenic erectile dysfunction. The trial administered 6 g/day of L-arginine for 3 months to 51 patients, compared to placebo in 47 patients with vasculogenic ED, measuring IIEF-6 score and cavernous artery peak systolic flow velocity (PSV) at dynamic penile duplex ultrasonography. L-arginine supplementation for 3 months significantly increased IIEF-6 score in the overall cohort (p < 0.0001) and in subgroups of mild–moderate and severe vasculogenic ED; PSV was significantly increased in the overall cohort and in patients with mild–moderate, but not severe, vasculogenic ED; at study completion, 74% of patients improved ED degree category.
The study's conclusion stated that supplementation with relatively high doses of L-arginine for 3 months significantly improved penile erectile function as assessed by both IIEF-6 score and PSV in patients with mild-moderate vasculogenic ED, suggesting that L-arginine might be an alternative treatment in mild-moderate vasculogenic ED patients experiencing adverse effects or with contraindications for chronic treatment with PDE5 inhibitor compounds.
There is research evidence suggesting that L-arginine can improve male reproductive abnormalities and can be useful in the treatment of some forms of male infertility and erectile dysfunction.
Strength of evidence for erectile dysfunction: Moderate for vasculogenic (arterial) ED of mild-to-moderate severity, based on at least one well-designed RCT. Evidence is weaker for severe ED or non-vasculogenic aetiology.
When L-arginine is cleaved to nitric oxide and L-citrulline by nitric oxide synthase, these compounds may have positive effects on glucose metabolism and beneficial action on the cardiovascular system. Increasing experimental and clinical data indicate that L-arginine supplementation may be helpful in managing disturbed metabolism in obesity, regulating arterial blood pressure, or alleviating type 2 diabetes symptoms, though the mechanisms underlying these effects have not been sufficiently elucidated. Available literature suggests that L-arginine may have beneficial effects on human health; however, some studies found that higher dietary L-arginine is associated with worsening of an existing disease or may be a potential risk factor for the development of some diseases.
Strength of evidence for diabetes: Preliminary. Findings are mixed, with the direction of benefit depending on dose, pre-existing metabolic status, and the arginine:arginase pathway balance.
Previous studies have shown that L-arginine supplementation improves respiratory function and exercise tolerance in patients with pulmonary diseases and in those with congestive heart failure as well as in heart transplant recipients. A study specifically investigated the potential beneficial effect of six weeks of oral L-arginine supplementation on endurance exercise in patients with chronic stable heart failure. The purpose of the study was to determine the potential beneficial effect of six weeks of oral L-arginine supplementation on endurance exercise, an important determinant of daily-life activity in patients with chronic stable heart failure.
Strength of evidence for heart failure: Preliminary to moderate; limited by small sample sizes in individual trials and the complexity of heart failure as a heterogeneous syndrome.
L-arginine has been shown to mediate NO production with strong antioxidant properties, scavenging free radicals and reducing oxidative stress. Reviews assess the wider implications of L-arginine supplementation in mitigating oxidative stress and preserving vascular function. For malic acid, dietary malic acid supplementation increased circulating activities of total antioxidant capacity markers and glutathione peroxidase (GSH-Px), indicating that malic acid enhanced antioxidant capacity in experimental models.
Strength of evidence for antioxidant effects: Predominantly preclinical (animal and in vitro). Human evidence remains limited.
An emerging application involves L-arginine supplementation in post-acute sequelae of COVID-19. A single-blind randomised controlled trial assessed the effects of 28-day oral supplementation with L-arginine plus vitamin C on physical performance, muscle strength, endothelial function, fatigue persistence, and systemic L-arginine bioavailability in adults with long COVID. This area represents a recently opened line of investigation and the evidence base remains early-stage.
No clinical trial has directly investigated diarginine malate as a compound at a specific dose. All dosage data presented below come from studies of L-arginine in its various forms (free base, hydrochloride, or in combination), and from studies of malate-containing compounds. The arginine dose delivered by diarginine malate would approximate two moles of arginine per mole of the compound, accounting for the molecular weight differential.
Clinical data on adverse effects cover a wide span of arginine intakes from 3 g/day to over 100 g/day; single doses of 3–6 g rarely provoked side effects in healthy athletes, though the standard of reporting adverse effects such as nausea, vomiting, and diarrhoea was variable across studies. L-arginine (but not lysine, ornithine, or D-arginine) induces water and electrolyte secretion mediated by NO, which acts as an absorbagogue at low concentrations and a secretagogue at high concentrations; reports of diarrhoea following oral administration of arginine have been noted.
Although there is unregulated consumption of oral L-arginine supplements, the safety and efficacy, as well as evidence-based daily dose ranges and durations for different conditions, have not been fully established.
Common side effects include diarrhoea and an upset stomach, especially with high doses. Gastrointestinal effects are characteristically dose-dependent: lower doses (3–6 g/day) are generally well tolerated in most adults, while higher doses increase the risk significantly.
When high doses of L-arginine are ingested, NO reacts with superoxide anions to form peroxynitrite, a strong oxidant that can cause cell damage, and the accumulation of superoxide anion exacerbates oxidative stress, leading to cardiomyocyte damage and cardiac dysfunction. Low doses (≤0.5 g/kg) of L-arginine can improve blood lipid levels, whereas high doses (≥1 g/kg) of L-arginine can exacerbate oxidative stress and cause myocardial damage. These findings were specifically noted in the context of patients with type 2 diabetes mellitus, a population that may be at heightened risk.
The interactions that matter most include nitrates (nitroglycerin, isosorbide): both arginine and nitrates work through the nitric oxide pathway, and combining them can cause a sharp, potentially dangerous drop in blood pressure; this combination should be avoided without medical supervision.
Blood-pressure-lowering medications present a clinically important interaction class. Blood pressure medications including ACE inhibitors, beta-blockers, and calcium channel blockers may have their effect amplified by arginine, and adding arginine without adjusting medication can cause hypotension — dizziness, lightheadedness, or fainting.
L-arginine supplements may interact with drugs that lower blood pressure, including sildenafil (Viagra). This is pharmacologically important because sildenafil and related phosphodiesterase-5 inhibitors also act through the NO/cGMP pathway; concurrent use may produce additive hypotensive effects.
Additional medication classes that may interact with L-arginine — based on shared physiological pathways — include blood-thinning agents, diabetes medications, and diuretics, specifically: blood-thinning medications such as clopidogrel, enoxaparin, heparin, and warfarin; diabetes medications such as insulin and glipizide; and medications that increase blood flow such as nitroglycerin and isosorbide; as well as diuretic medications such as amiloride, triamterene, and spironolactone.
Individuals with pre-existing herpes simplex virus infection are commonly advised to use caution, as high intakes of arginine-rich substances have been associated anecdotally with viral reactivation, though controlled clinical evidence on this specific interaction with supplemental arginine is limited. Subjects with pre-existing high cholesterol and other cardiovascular or metabolic risk factors are known to have both reductions in vascular reactivity and altered eNOS activity, which may affect how they respond to arginine supplementation.
The dosage that is beneficial for a person may depend on their age, existing health conditions, and the reason for supplementation.
It bears explicit emphasis that no published human safety study has investigated diarginine malate (Nitrous Malate™) as a specific compound. Safety inferences must be drawn from the separate bodies of literature on L-arginine and on malic acid. The malate component — being an endogenous metabolic intermediate ubiquitously present in human physiology — is not associated with significant toxicity at nutritionally relevant doses. The L-arginine component carries the pharmacologically active and interaction-relevant properties described above. Oral L-arginine at higher doses and longer treatment durations significantly alters various enzymes and metabolites in the arginine metabolic pathways; further studies with differing doses and durations are needed to allow for a better understanding of oral L-arginine uses, and an evidence-based safe and effective dose range and duration.
Condiciones de salud que Nitrato Malato (TM) Diarginina Malato puede ayudar a apoyar.
Diarginine malate delivers two molecules of L-arginine (the direct eNOS substrate) with malate (a Krebs cycle intermediate supporting arginine regeneration). Both components have established mechanistic relevance to NO synthesis: arginine as the NOS substrate and malate as a supporter of the argininosuccinate-mediated arginine recycling pathway.
Sistemas corporales que Nitrato Malato (TM) Diarginina Malato puede ayudar a apoyar.
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