Enhanced nitrate, elemental metal and amino acid compositions and methods of use

Abstract

The present disclosure relates to methods of at least reducing, preventing, or even reversing the formation of nitrosamines to improve athletic performance in a subject, and to increase aerobic capacity, stamina, strength, endurance, and / or time to exhaustion in a subject. The present disclosure also relates to methods of at least reducing, preventing, or even reversing the formation of nitrosamines to improve athletic performance in a subject, and to increase aerobic capacity, stamina, strength, endurance, and / or time to exhaustion in a subject. - (source of nitrite anion NO2 - In another embodiment, the composition may also include an acid.

Description

[Technical field]

[0001] (CROSS REFERENCE TO RELATED APPLICATIONS) This application claims priority to U.S. Provisional Patent Application No. 63 / 159,990, filed March 11, 2021, the contents of each of which are incorporated by reference in their entirety herein. [Background technology]

[0002] (background) The formation of N-nitroso compounds is a multi-step process. In human nutrition, orally consumed nitrates are partially converted to nitrites after consumption. The nitrites then react with natural or synthetic organic amine compounds in food or water to form new combinations called N-nitroso compounds (either nitrosamines or nitrosamides).

[0003] N-nitrosamines are formed in this nitrosation reaction from primary, secondary, and tertiary amines and tertiary ammonium compounds (e.g., choline and carnitine). Most nitrosamines are brightly colored because the nitroso group is a strong chromophore.

[0004] Many of these N-nitroso compounds have been found to be carcinogenic in all animal species tested.

[0005] Nitrosamine formation by nitrite occurs at a much higher rate in acidic environments (such as the acidic environment of the stomach). At least 75% of the 120 N-nitroso compounds have been found to be carcinogenic to animals.

[0006] There are also other nitrosamines to which people may be exposed from some source, e.g., contaminants in drinking water, contaminants in over-the-counter medications, such as N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), N-nitrosodibutylamine (NDBA), N-nitrosopiperidine (NPIP), N-nitrosopyrrolidine (NPYR), and N-nitrosothiazolidine (NTHZ). (The popular medication ranitidine was removed from the market by the FDA in 2019.) Summary of the Invention [Problem to be solved by the invention]

[0007] Thus, concerns have arisen, and still exist, regarding the co-administration of nitrates and nitrites with amino acids. [Means for solving the problem]

[0008] (Summary of the invention) The present disclosure relates to compositions, kits, and methods for reducing nitrosamine formation from amine moiety-containing compounds.

[0009] A method for reducing nitrosamine formation from an amine moiety-containing compound is disclosed, the method comprising co-administering the amine moiety-containing compound with an elemental metal and a nitrate and / or nitrite.

[0010] In some implementations, the amine moiety-containing compound is an amino acid (e.g., in salt form). In other implementations, the amine moiety-containing compound is selected from the group consisting of agmatine, alanine, β-alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, GABA, histidine, isoleucine, leucine, lysine, methionine, phenyl-β-alanine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine. In some implementations, the elemental metal is selected from the group consisting of elemental magnesium, elemental calcium, elemental lithium, elemental zinc, elemental sodium, elemental potassium, elemental beryllium, elemental rubidium, elemental cesium, elemental aluminum, elemental gallium, elemental indium, elemental tin, elemental bismuth, elemental scandium, elemental titanium, elemental vanadium, elemental chromium, elemental manganese, elemental cobalt, elemental manganese, elemental scandium, elemental titanium, elemental nickel, elemental copper, elemental zinc, elemental yttrium, elemental zirconium, elemental niobium, elemental molybdenum, elemental technetium, elemental ruthenium, elemental rhodium, elemental palladium, elemental silver, elemental cadmium, elemental lanthanum, elemental hafnium, elemental tantalum, elemental tungsten, elemental rhenium, elemental osmium, elemental iridium, elemental platinum, elemental gold, and elemental manganese.

[0011] In some implementations, the method further comprises administering an acid, which is co-administered with the amine moiety-containing compound, the elemental metal, and the nitrate and / or nitrite, In such implementations, nitrosamine formation of the amine moiety-containing compound is prevented.

[0012] Also disclosed is a method for reducing nitrosamine formation in a composition comprising an amine moiety-containing compound and a nitrosating agent, the method comprising adding an elemental metal to the composition.

[0013] In some implementations, the nitrosating agent is selected from the group consisting of nitrates, nitrites, nitric oxide, and nitrogen dioxide. In certain implementations, the nitrosating agent is nitric oxide and / or nitrogen dioxide.

[0014] In some implementations, ingestion of a composition that includes the elemental metal results in the formation of reduced amounts of nitrosamines compared to ingestion of a composition that does not include the elemental metal.

[0015] In some implementations, the elemental metal is at least one metal selected from the group consisting of elemental magnesium, elemental calcium, elemental lithium, elemental zinc, elemental sodium, elemental potassium, elemental beryllium, elemental rubidium, elemental cesium, elemental aluminum, elemental gallium, elemental indium, elemental tin, elemental bismuth, elemental scandium, elemental titanium, elemental vanadium, elemental chromium, elemental manganese, elemental cobalt, elemental manganese, elemental scandium, elemental titanium, elemental copper, elemental zinc, elemental yttrium, elemental zirconium, elemental niobium, elemental molybdenum, elemental technetium, elemental ruthenium, elemental rhodium, elemental palladium, elemental silver, elemental cadmium, elemental lanthanum, elemental hafnium, elemental tantalum, elemental tungsten, elemental rhenium, elemental osmium, elemental iridium, elemental platinum, elemental gold, and elemental manganese.

[0016] In some implementations, the amine moiety-containing compound is an amino acid (eg, in salt form), and the composition does not form nitrosamines upon ingestion.

[0017] In some implementations, the amine moiety-containing compound is selected from the group consisting of agmatine, alanine, β-alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, GABA, histidine, isoleucine, leucine, lysine, methionine, phenyl-β-alanine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine.

[0018] In certain implementations, the method further includes the step of adding an acid to the composition.

[0019] Also disclosed are compositions with reduced nitrosamine formation, the compositions including an elemental metal, a nitrate and / or nitrite, and an amine moiety-containing compound.

[0020] In some implementations, the composition further comprises an acid.

[0021] In some implementations, the elemental metal is at least one metal selected from the group consisting of elemental magnesium, elemental calcium, elemental lithium, elemental zinc, elemental sodium, elemental potassium, elemental beryllium, elemental rubidium, elemental cesium, elemental aluminum, elemental gallium, elemental indium, elemental tin, elemental bismuth, elemental scandium, elemental titanium, elemental vanadium, elemental chromium, elemental manganese, elemental cobalt, elemental manganese, elemental scandium, elemental titanium, elemental copper, elemental zinc, elemental yttrium, elemental zirconium, elemental niobium, elemental molybdenum, elemental technetium, elemental ruthenium, elemental rhodium, elemental palladium, elemental silver, elemental cadmium, elemental lanthanum, elemental hafnium, elemental tantalum, elemental tungsten, elemental rhenium, elemental osmium, elemental iridium, elemental platinum, elemental gold, and elemental manganese.

[0022] In some implementations, the amine moiety-containing compound is an amino acid (e.g., an amino acid in a salt form). In other implementations, the amine moiety-containing compound is selected from the group consisting of agmatine, alanine, β-alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, GABA, histidine, isoleucine, leucine, lysine, methionine, phenyl-β-alanine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0023] (Detailed Description) Detailed aspects and applications of the present disclosure are described below in the following Detailed Description of the Technology. Unless specifically stated otherwise, it is intended that the terms and phrases in the specification and claims be given their plain, ordinary and accustomed meaning to those skilled in the applicable art.

[0024] In the following description, for the purpose of explanation, many specific details are shown to provide a complete understanding of various aspects of the present disclosure. However, it is understood by those skilled in the relevant field that the implementation of the technology disclosed herein can be carried out without using these specific details. It should be noted that there are many different alternative configurations, devices and technologies to which the disclosed technology can be applied. The full scope of the technology disclosed herein is not limited to the following examples.

[0025] The singular forms "a," "an," and "the" include plural referents unless the context clearly indicates otherwise. Thus, for example, reference to "a step" includes a reference to one or more such steps.

[0026] As used herein, the term "about" refers to a deviation of no more than 5% from a given value, for example, a deviation of 3%, 2%, 1%, 0.5%, or 0.1% from the given value.

[0027] As used herein, the term "acceptable" is a phrase used in its broadest sense and may describe a composition component that meets the standards of the United States Food and Drug Administration (FDA), the United States Pharmacopeia (USP), the United States Department of Agriculture (USDA) standards for food-grade substances, the generally accepted standards of the dietary supplement industry, industry standards, plant standards, or standards established by any individual.These standards may describe the acceptable range of the characteristics of the composition component (e.g., the edibility, toxicity, pharmacological action, or any other characteristics of the chemicals, compositions, or preparations used in implementing the composition).

[0028] As used herein, "amino acid" is a term used in its broadest sense and may refer to an amino acid in its many different chemical forms, including its free form (e.g., L-cysteine), its physiologically active salts (e.g., its nitrates), its combinations with its various salts, its tautomeric and / or isomeric forms, its ester and amide forms, and / or its decarboxylation products, including, by way of non-limiting example, agmatine, alanine, β-alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenyl-β-alanine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine.

[0029] As used herein, the term "amine moiety-containing compound" refers to a compound that contains a functional group that includes a basic nitrogen atom having a lone pair of electrons, such as a primary amine group (-NH-R, also known as an amino group), a secondary amine group (-NH-R 1 -R 2 ), or a tertiary amine group (-NR 1 -R 2 -R 3 ) Amine moiety-containing compounds thus encompass the essential amino acids as well as gamma-aminobutyric acid (GABA).

[0030] As used herein, the term "composition" refers to both a mixture of ingredients or components, as well as a combination of capsules containing various ingredients or components. Thus, in one particular implementation, the composition includes separate capsules that are packaged together and intended to be taken together.

[0031] As used herein, the term "elemental metal" refers to the neutral charge state of a metal element, in other words, its uncharged elemental form and not its salt form or charged form (exemplary salt forms and charged forms include the oxide, hydroxide, carbonate, chloride, lactate, citrate, aspartate, glycinate, and gluconate of the metal). As such, as used herein, an elemental metal and a salt of the same metal are different entities. The statement of a composition comprising an elemental metal cannot be satisfied by the presence of a metal salt, and vice versa. For example, a composition consisting of magnesium citrate is not a composition comprising elemental magnesium, despite any statement that magnesium citrate provides a certain amount of elemental magnesium.

[0032] The elemental metals described herein include elemental magnesium, elemental calcium, elemental lithium, elemental zinc, elemental sodium, elemental potassium, elemental beryllium, elemental rubidium, elemental cesium, elemental aluminum, elemental gallium, elemental indium, elemental tin, elemental bismuth, elemental scandium, elemental titanium, elemental vanadium, elemental chromium, elemental manganese, elemental cobalt, elemental manganese, elemental scandium, elemental titanium, elemental nickel, elemental copper, elemental zinc, elemental yttrium, elemental zirconium, elemental niobium, elemental molybdenum, elemental technetium, elemental ruthenium, elemental rhodium, elemental palladium, elemental silver, elemental cadmium, elemental lanthanum, elemental hafnium, elemental tantalum, elemental tungsten, elemental rhenium, elemental osmium, elemental iridium, elemental platinum, elemental gold, elemental manganese, and elemental iron.

[0033] As used herein, "pump" refers to the sensation of better blood flow as described by the athlete, which can be confirmed by user experience as well as scientific methods (e.g., measuring muscle circumference after exercise, Doppler ultrasound measurement of blood flow, measuring vein size with a vein viewer, etc.).

[0034] As used herein, the term "nitrosating agent" refers to an agent that causes the nitrosation of another compound. For example, nitrosating agents include the nitrite anion (NO - ), a source of nitrate anion (NO3 - ), nitric oxide (NO), and nitrogen dioxide (NO2).

[0035] The inventors have been commercially successful in inventing the amino acids with nitrates or nitrites of the present invention due to the health and other benefits of nitrate supplementation (e.g., lowering blood pressure, improving endothelial function, and enhancing athletic performance).There remain dosage limitations for the nitrite products to ensure safety compared to nitrates, and therefore there is a need for further improvements.

[0036] Nitrate (nitrate anion NO3 - (source of nitrite anion NO2 - Disclosed herein are novel compositions with reduced risk of nitrosamine formation, comprising a source of nitrosamines (source of nitrosamines), an amine moiety-containing compound, and an elemental metal. In some implementations, the amine moiety-containing compound is an amino acid. In other implementations, the amine moiety-containing compound is selected from the group consisting of agmatine, alanine, β-alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, GABA, histidine, isoleucine, leucine, lysine, methionine, phenyl-β-alanine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine. In other implementations, the composition may also include an acid.

[0037] In some implementations, the nitrate and / or nitrite is a nitrate and / or nitrite of an amino acid or amino acid derivative (e.g., citrulline nitrate, citrulline nitrite, betaine nitrate, betaine nitrite), an inorganic nitrate (e.g., magnesium nitrate, sodium nitrate, potassium nitrate, calcium nitrate, lithium nitrite, magnesium nitrite, sodium nitrite, potassium nitrite, calcium nitrite, and lithium nitrite, or mixed salts, co-crystal formulations, and hydrates thereof), or a natural source. For natural sources, the nitrate and / or nitrite is concentrated and / or isolated from a natural source (e.g., a plant nitrate source or a plant nitrite source). Examples of natural nitrate and / or nitrite sources include, but are not limited to, beet juice, beet juice powder, concentrated beet juice powder, celery powder, spinach extract and red spinach extract, and Amaranthus extract. In certain implementations, the nitrate and / or nitrite content of the natural nitrate and / or nitrite source is standardized to provide a sufficient amount of nitrate. In some implementations, the composition includes more than one source or form of nitrate and / or nitrite.

[0038] In some implementations, the elemental metal is at least one metal selected from the group consisting of elemental magnesium, elemental calcium, elemental lithium, elemental zinc, elemental sodium, elemental potassium, elemental beryllium, elemental rubidium, elemental cesium, elemental aluminum, elemental gallium, elemental indium, elemental tin, elemental bismuth, elemental scandium, elemental titanium, elemental vanadium, elemental chromium, elemental manganese, elemental cobalt, elemental manganese, elemental scandium, elemental titanium, elemental copper, elemental zinc, elemental yttrium, elemental zirconium, elemental niobium, elemental molybdenum, elemental technetium, elemental ruthenium, elemental rhodium, elemental palladium, elemental silver, elemental cadmium, elemental lanthanum, elemental hafnium, elemental tantalum, elemental tungsten, elemental rhenium, elemental osmium, elemental iridium, elemental platinum, elemental gold, and elemental manganese.

[0039] In certain implementations, the composition comprises elemental iron as its elemental metal component, β-alanine and proline as its amine moiety-containing compound component, and citrulline nitrate and betaine nitrate as its nitrate and / or nitrite component. In some implementations, the composition further comprises citrulline as an additional amine moiety-containing compound component, and citrulline nitrate as an additional nitrate and / or nitrite component. In certain implementations, the composition further comprises at least one antioxidant, for example, the composition can further comprise black tea leaf extract, ferulic acid, and L-theanine. In some implementations, the composition further comprises caffeine. The composition can also comprise calcium and folate.

[0040] In other particular implementations, the composition comprises elemental iron as its elemental metal component, cysteine ​​as its amine moiety-containing compound component, and amaranth extract as its nitrate and / or nitrite component. In some implementations, the composition further comprises an acid, such as ascorbic acid (vitamin C). In particular implementations, the composition further comprises at least one antioxidant. For example, the composition may further comprise theanine. In some implementations, the composition may also comprise calcium and folate / 5-MTHF and / or potassium molybdate.

[0041] Nitrate (nitrate anion NO3 - (source of nitrite anion NO2 - It was also surprisingly discovered that co-administration of the nitrate anion (NO3 source) with other elemental metals (e.g., elemental magnesium and elemental zinc) also increased the effectiveness of the nitrate and / or nitrite. Thus, the present disclosure also provides a method for the preparation of a nitrate anion (NO3 source) in providing a beneficial effect to a subject. - ) and / or nitrite anion (NO2 - For example, the method may improve athletic performance in a subject. In some aspects of the method of improving athletic performance in a subject, aerobic capacity, stamina, muscle strength, endurance, and / or time to exhaustion in the subject is increased.

[0042] The physiological effects resulting from the ingestion of the disclosed compositions can occur within 15 minutes, and as little as 5 minutes, after ingestion of the compositions. This time frame is consistent with when pre-workout supplements are typically administered. Although most pre-workout supplements are recommended to be taken about 30 minutes before training, users often take their supplements just before training. Thus, the disclosed compositions are more compatible with the habits of athletes and other pre-workout supplement users. Instead of needing to remember to take their nitrate supplement 3 hours before training to maximize the benefits of nitrate supplementation, users only need to take the disclosed compositions a few minutes (e.g., 5 minutes) before training. The minimal delay between the ingestion of the disclosed compositions and the physiological effects resulting from inorganic nitrates can be easily met by the warm-up time at the start of training. Thus, in certain implementations of the method for improving athletic performance or increasing stamina, strength, endurance, and / or time to exhaustion, the subject is administered a combination of an elemental metal and a nitrate (nitrate anion NO3 - (source of nitrite anion NO2 - (a source of omega-3 fatty acids) is co-administered within 30 minutes prior to a session of physical activity or training.

[0043] Due to the rapid and powerful action of the disclosed compositions, these compositions may be used for all situations where the effects of nitrates are beneficial and a novel rapid effect is desired.

[0044] The elemental metal is an alkaline earth metal, an alkali metal, or a transition metal. In some implementations, the elemental metal can be elemental magnesium, elemental calcium, elemental lithium, elemental zinc, elemental iron, etc. In some implementations, the nitrate (nitrate anion NO3 -The nitrate anion (source of nitrate) can be a salt of nitric acid, such as potassium nitrate, sodium nitrate, magnesium nitrate, proline nitrate, betaine nitrate, beta-alanine nitrate, citrulline nitrate, etc. In other aspects, the nitrate anion is a vegetable nitrate source. In other implementations, the composition can further include an acid. In certain implementations, the acid is a liquid acid, such as hydrochloric acid, phosphoric acid, nitric acid, or sulfuric acid. In other implementations, a solid acid (e.g., citric acid) is used, which is dissolved in water. The acid can be dissolved in water before adding the elemental metal and nitrate.

[0045] In some implementations, the composition comprises an effective amount of nitrate (nitrate anion NO3 - (source of nitrite anion NO2 - and an effective amount of an elemental metal, which is capable of exerting its beneficial effect by providing its nitrate anion (NO3 - ) to support / enhance the effectiveness of the nitrate anion NO3 - (source of nitrite anion NO2 - An effective amount of a source of nitrate (NO3) in the composition is an amount sufficient to cause vasodilation in a subject to enhance athletic performance, etc. - (source of nitrite anion NO2 - An effective amount of nitrate anion (NO3 - ), but the effective amount of the elemental metal is more effective than its nitrate (nitrate anion NO3) in causing vasodilation or increasing exercise performance in a subject. - ) and / or nitrite (a source of nitrite anion (NO2 - (source)) in a quantity sufficient to support the

[0046] In one particular embodiment, the composition comprises about 1 mg to about 900 mg of elemental magnesium and nitrate (nitrate anion NO3 - (source of nitrite anion NO2 - The inorganic nitrate source contains about 5 mg to about 2000 mg of nitrate anion (NO3 - In some aspects, the nitrate (nitrate anion NO3 - (source of nitrite anion NO2 - The source of nitrate anion (NO3) is about 30mg to 2000mg. - ), about 50mg to about 2000mg of nitrate anion (NO3 - ), about 5 mg to about 1000 mg of nitrate anion (NO3 - ), about 30 mg to about 1000 mg of nitrate anion (NO3 - ), about 50mg to about 1000mg of nitrate anion (NO3 - ), about 5 mg to about 600 mg of nitrate anion (NO3 - ), about 30 mg to about 600 mg of nitrate anion (NO3 - ), about 50mg to about 600mg of nitrate anion (NO3 - ), about 5 mg to about 500 mg of nitrate anion (NO3 - ), about 30 mg to about 500 mg of nitrate anion (NO3 - ), or about 50 mg to about 500 mg of nitrate anion (NO3 - In one particular implementation, the nitrate (nitrate anion NO3 - (source of nitrite anion NO2 - The source of nitrate is a salt of nitrate (e.g., magnesium nitrate or proline nitrate).

[0047] In some implementations, the nitrate (nitrate anion NO3 - (source of nitrite anion NO2 - The molar ratio of the elemental metal to the amount of nitrate (NO3) is at least 2:1.- (source of nitrite anion NO2 - The dose of the nitrate anion (NO3) may be adjusted according to the weight, age, and health status of the subject. Typically, normotensive subjects receive less elemental metals and nitrate anions (NO3) than hypertensive subjects. - ), and hypotensive subjects require even less elemental metals and nitrate anions (NO3 - In some implementations, the composition requires only 1 mg to 5000 mg of NO3 - and / or NO2 - and 1 mg to 10,000 mg of elemental metal. In another embodiment, the composition comprises 5 mg to 200 mg of NO3 - and / or NO2 - and 5 mg to 1000 mg of elemental metal. In some embodiments, the amount of elemental metal in the composition is between 1 mg and 800 mg, or between 5 mg and 400 mg. In some embodiments, the nitrate (nitrate anion NO3 - (source of nitrite anion NO2 - The amount of niacin (source) is between 30 mg and 2000 mg, or between 50 mg and 600 mg.

[0048] In some implementations, the composition is in the form of a capsule, cachet, pill, tablet, powder, granule, pellet, bead, particle, troche, lozenge, pastille, liquid, elixir, syrup, tincture, suspension, emulsion, mouthwash, spray, drop, ointment, cream, gel, paste, transdermal patch, suppository, pessary, cream, gel, paste, foam, and combinations thereof. The composition may further comprise an acceptable additive and / or an acceptable carrier. The acceptable additive may be selected from at least one member selected from the group consisting of solubilizers, enzyme inhibitors, anticoagulants, antifoaming agents, antioxidants, colorants, cooling agents, cryoprotectants, hydrogen bonding agents, flavoring agents, plasticizers, preservatives, sweeteners, and thickeners. The acceptable carrier may be selected from at least one member selected from the group consisting of excipients, lubricants, binders, disintegrants, diluents, extenders, solvents, suspending agents, dissolution aids, isotonicity agents, buffering agents, soothing agents, and amphiphilic lipid delivery systems. In some implementations, the composition is in a form suitable for oral administration. In other implementations, the composition is in a form suitable for inhalation of the gas generated when contacted with an acidified solvent.

[0049] The elemental metal in the composition can be in any form, for example, powder or granule. In a particular implementation of the composition, the nitrate and / or nitrite are packaged in a capsule, cachet, pill, tablet, powder, granule, pellet, bead, particle, lozenge, or lozenge, and the elemental metal is packaged in a capsule, cachet, pill, tablet, powder, granule, pellet, bead, particle, lozenge, or lozenge. In another implementation, the nitrate and / or the nitrite are packaged in a capsule, cachet, pill, tablet, powder, granule, pellet, bead, particle, lozenge, or lozenge, and the elemental metal is packaged in a capsule, cachet, pill, tablet, powder, granule, pellet, bead, particle, lozenge, or lozenge, and the acid is packaged separately from the nitrate and / or nitrite and the elemental metal. In some implementations, the nitrate and / or nitrite, the elemental metal, and the acid are in solid form. In certain implementations, the nitrate and / or nitrite and the elemental metal are packaged together, for example, in a capsule, cachet, pill, or tablet.

[0050] In yet another embodiment, the composition comprises nitrite anion (NO - ) source of nitrate anion (NO3 - For example, the composition may include a source of nitrite anion (NO2 - In some implementations, the composition includes a source of nitrite anions, an amino acid, an elemental metal, and an acid.

[0051] In some implementations, the elemental metal in the composition is coated or microencapsulated with a suitable material that is poorly soluble in water but soluble in the acidic environment of the stomach (e.g., magnesium oxide, cellulose polymers, alginates (e.g., calcium alginate), or aluminum hydroxide).

[0052] In some implementations, proline nitrate is the nitrate in the composition (nitrate anion NO3 - (source of nitrite anion NO2 - In some implementations, magnesium nitrate is the source of nitrate (nitrate anion NO3 - (source of nitrite anion NO2 - In such implementations, the magnesium nitrate may be anhydrous or hydrated. The degree of hydration of the magnesium nitrate is between one and six water molecules per magnesium nitrate molecule. In certain implementations, magnesium nitrate hexahydrate is the salt of nitric acid in the composition.

[0053] In some implementations, the disclosed compositions further comprise an acid. The acid is added to ensure that the stomach pH remains acidic upon ingestion of the composition. The acid component can be any acid suitable for human consumption, such as citric acid, succinic acid, malic acid, ascorbic acid, or tartaric acid. In some implementations, the acid is in solid form, such as a powder. Thus, the amount of acid in the composition in some implementations is between 50mg and 20,000mg, between 50mg and 2000mg, between 50mg and 1000mg, between 100mg and 20,000mg, between 100mg and 2000mg, between 100mg and 1000mg, between 200mg and 20,000mg, between 200mg and 2000mg, between 200mg and 1000mg, between 300mg and 20,000mg, between 300mg and 2000mg, between 300mg and 1000mg, between 500mg and 20,000mg, between 500mg and 2000mg, or between 500mg and 1000mg. In some implementations, the acid component of the composition is vinegar. In some implementations, the disclosed compositions do not include an acid, but the compositions are administered with an acid. For example, the compositions are co-administered with an acidic solution having a pH between 2 and 6, such as a dilute vinegar or citric acid solution. In some implementations, the acidic solution is dilute acetic acid, nitric acid, sulfuric acid, or the like.

[0054] The disclosed compositions may be in the form of a capsule, tablet, pill, liquid, liquid suspension, vapor, powder, granulate, pulverulence, or combinations thereof. In one implementation, the disclosed compositions are in solid form. In some implementations, the elemental metal and nitrate (nitrate anion NO3 - (source of nitrite anion NO2 - In some implementations, the acid and / or amino acid is combined with the elemental metal and nitrate ion source in a capsule or tablet. In other implementations, the acid and / or amino acid is in a separate tablet / tablets or capsule / capsules from the elemental metal and nitrate ion source. The nitrate (nitrate anion NO3- (source of nitrite anion NO2 - The enhanced activity of co-administration of an elemental metal and an amino acid with a source of nitrate (NO3) is not reduced when the subject takes them separately (e.g., by co-administration of three separate capsules). Thus, in some implementations, the compositions described herein contain nitrate (NO3) and / or nitrate anion (NO3). - (source of nitrite anion NO2 - The compositions further include a capsule containing an elemental metal, a capsule containing an amino acid, and a capsule containing an acid. In certain implementations of the composition further comprising an acid, the composition may further comprise a capsule containing the acid.

[0055] It is noted that the powder form of the disclosed composition loses some of its efficacy when administered in water prior to ingestion. Thus, administration of the powder form of the composition should be done with minimal exposure time to water. Ideally, the exposure of the powdered composition to water should be less than 1 minute, less than 5 minutes, less than 10 minutes, less than 15 minutes, or less than 30 minutes. For example, instead of dissolving the powdered composition in water and drinking the mixture, the subject should wash it down with water after ingesting the powdered composition. Alternatively, the subject may mix the composition in water and consume it immediately. Also, if the composition is added to an alkaline mixture (pH greater than 7) (e.g., water mixed with baking soda), it may retain its efficacy for at least 10 minutes prior to ingestion, which is typically enough time for a person to mix a pre-workout drink and consume it.

[0056] In some implementations, the composition further comprises a suitable pharma- ceutically acceptable coating to prevent moisture from penetrating the tablet and / or the excipient. Non-limiting examples of the pharma-ceutically acceptable coating include waxes, polymers, solid fatty acids, and the like. Non-limiting examples of the excipient include carriers, excipients, binders, colorants, flavorings, preservatives, buffers, diluents, and combinations thereof. In some aspects, the excipient is a pharma-ceutically acceptable excipient or an acceptable food excipient.

[0057] The present disclosure also relates to a method of reducing nitrosamine formation in a composition comprising an amine moiety-containing compound and a nitrosating agent, the method comprising adding an elemental metal to a composition comprising the amine moiety-containing compound and a nitrosating agent. In certain implementations, the nitrosating agent is selected from the group consisting of nitrates, nitrites, nitric oxide, and nitrogen dioxide. As shown in the examples, the presence of the elemental metal in a composition comprising the amine moiety-containing compound and a nitrosating agent reduces the amount of nitrosamines formed in the composition. In certain implementations, the addition of the elemental metal to the composition can prevent nitrosamine formation. As also shown in the examples, if the amine moiety-containing compound has undergone nitrosation, the addition of the elemental metal to the composition can reverse the reaction. Thus, ingestion of such a composition comprising the amine moiety-containing compound, the nitrosating agent, and the elemental metal ultimately results in reduced nitrosamine formation, if any is formed at all.

[0058] Thus, a method for reducing nitrosamine formation of an amine moiety-containing compound is disclosed. The method includes co-administering the amine moiety-containing compound with an elemental metal and a nitrate and / or nitrite. In some implementations of the methods disclosed herein, the method further includes adding an acid to the composition, or co-administering the amine moiety-containing compound with an elemental metal, a nitrate and / or nitrite, and an acid. In certain implementations, the elemental metal is the metals magnesium, iron, zinc, and calcium. EXAMPLES

[0059] (Example) Example 1 To demonstrate the effectiveness of the above compositions and methods in reducing nitrosamine formation in simulated gastric conditions, 1 / 2 tablespoon of glycine was added to 100 ml of 0.1N HCl solution to form a clear solution. 0.1N HCl is commonly used in the art to simulate the acidic gastric conditions of the stomach. Then, 1 / 4 tablespoon of sodium nitrite was added while stirring at 200 rpm. The green nitrosation product, n-nitrosoglycine, was rapidly formed. After 1 hour, 1 / 4 teaspoon of elemental magnesium (granular) was added. After 30 minutes, the solution turned clear, indicating the removal of n-nitrosoglycine.

[0060] Example 2 To demonstrate the effectiveness of the above compositions and methods in reducing nitrosamine formation in simulated gastric conditions, ½ tablespoon of l-tyrosine was added to 100 ml of 0.1N HCl solution to form a white solution. ¼ tablespoon of sodium nitrite was then added with stirring at 200 rpm. The orange-yellow nitrosation product, n-nitrosotyrosine, was rapidly formed. After 1 hour, ¼ teaspoon of elemental magnesium (granular) was added. After 30 minutes, the solution turned white, indicating removal of n-nitrosotyrosine.

[0061] Example 3 To demonstrate the effectiveness of the above compositions and methods in reducing nitrosamine formation in simulated gastric conditions, 1 / 2 tablespoon of l-cysteine ​​was added to 100 ml of 0.1N HCl solution to form a white solution. Then, 1 / 4 tablespoon of sodium nitrite was added while stirring at 200 rpm. The pink S-nitrosation product, S-nitrosocysteine, was rapidly formed. After 1 hour, 1 / 4 teaspoon of elemental magnesium (granular) was added. After 30 minutes, the solution turned white, indicating the removal of S-nitrosocysteine.

[0062] Example 4 In one implementation, the composition includes 1 g to 2 g of amaranth extract (providing 10% to 90% nitrate), 50 mg to 1000 mg of vitamin C, 50 mg to 1000 mg of magnesium oxide, 10 mg to 1000 mg of L-cysteine, 50 mg to 1000 mg of theanine, 5 mg to 100 mg of elemental iron, 0.5 mg to 30 mg of folate / 5-MTHF, and 1 mcg to 500 mcg of potassium molybdate.

[0063] In yet another implementation, the composition is an athletic performance enhancing product (pre-workout product) intended to improve athletic performance indicators (e.g., power, endurance, vasodilation, and pumps) (see Table 1). The pre-workout product contains an effective amount of nitrate (NO3 - ) and amino acids. Each serving of the composition provides 5g of amino acid nitrates (including proline nitrate and beta-alanine nitrate), which are enhanced with hydrogen-reduced elemental iron to further amplify the effects of the nitrates while minimizing nitrosamine formation. Additionally, each nitrate in the pre-workout product is provided with its regular counterpart (10g citrulline malate, 2g betaine anhydrous, and 2.6g beta-alanine). Other ingredients include a 1g dose of black tea extract, 200mg theanine, and 250mg caffeine for energy. [Table 1]

Claims

1. 1. A composition for use in a method for reducing nitrosamine formation from an amine moiety-containing compound, comprising an elemental metal and a nitrate and / or nitrite, said method comprising: co-administering said composition with said amine moiety-containing compound. wherein the elemental metal is selected from the group consisting of elemental magnesium, elemental iron, elemental zinc, elemental copper, elemental silver and elemental gold.

2. The composition of claim 1 , wherein the amine moiety-containing compound is an amino acid.

3. The composition of claim 2 , wherein the amino acid is in a salt form.

4. 2. The composition of claim 1, wherein the amine moiety-containing compound is selected from the group consisting of agmatine, alanine, β-alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, GABA, histidine, isoleucine, leucine, lysine, methionine, phenyl-β-alanine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine.

5. The composition described in any one of claims 1 to 4, wherein the method further comprises a step of administering an acid, wherein the acid is co-administered with the amine moiety-containing compound and the composition.

6. 6. The composition of claim 5, wherein nitrosamine formation of the amine moiety-containing compound is prevented.

7. 1. A method for reducing nitrosamine formation in a composition comprising an amine moiety-containing compound and a nitrosating agent selected from the group consisting of nitrates, nitrites, nitric oxide, and nitrogen dioxide, comprising: adding elemental metals to the composition; wherein the elemental metal is selected from the group consisting of elemental magnesium, elemental iron, elemental zinc, elemental copper, elemental silver and elemental gold.

8. The method of claim 7 further comprising the step of adding an acid to the composition.

9. 9. The method according to claim 7 or 8, wherein the nitrosating agent is nitric oxide and / or nitrogen dioxide.

10. The method according to claim 7 or 8, wherein the amine compound is an amino acid.

11. The method of claim 10, wherein the amino acid is in a salt form.

12. 12. The method of claim 11, wherein the composition does not form nitrosamines upon ingestion.

13. 12. The method of claim 11, wherein ingestion of the composition comprising the elemental metal forms reduced amounts of nitrosamines compared to ingestion of the composition not comprising the elemental metal.

14. 9. The method of claim 7 or 8, wherein the amine moiety-containing compound is selected from the group consisting of agmatine, alanine, β-alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, GABA, histidine, isoleucine, leucine, lysine, methionine, phenyl-β-alanine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine.

15. an elemental metal selected from the group consisting of elemental magnesium, elemental iron, elemental zinc, elemental copper, elemental silver and elemental gold; Nitrite and Amine moiety-containing compound A composition comprising:

16. The composition of claim 15 further comprising an acid.

17. 17. The composition of claim 15 or 16, wherein the amine moiety-containing compound is an amino acid.

18. 20. The composition of claim 17, wherein the amino acid is in a salt form.

19. 17. The composition of claim 15 or 16, wherein the amine moiety-containing compound is selected from the group consisting of agmatine, alanine, β-alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, GABA, histidine, isoleucine, leucine, lysine, methionine, phenyl-β-alanine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine.

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