EP4701445A1

EP4701445A1 - A dietary supplement combination and use thereof for improving muscle performance

Info

Publication number: EP4701445A1
Application number: EP24722140.1A
Authority: EP
Inventors: Behrooz Kasraee
Original assignee: Orivian Inc
Current assignee: Orivian Inc
Priority date: 2023-04-28
Filing date: 2024-04-23
Publication date: 2026-03-04
Also published as: WO2024223532A1

Abstract

The present disclosure relates generally to the use of an anabolic amino acid composition for the stimulation of muscle protein synthesis, muscle mass and strength. In particular, disclosed are compositions and methods of using the same for the prevention and / or treatment of a loss of any one of muscle mass, muscle strength, muscle function, and physical function, or any combination thereof, for human, and especially adult or animals such as mammals.

Description

A DIETARY SUPPLEMENT COMBINATION AND USE THEREOF FOR IMPROVING MUSCLE PERFORMANCE

FIELD OF THE INVENTION

The present disclosure relates generally to the use of an anabolic amino acid composition for the stimulation of muscle protein synthesis, muscle mass and strength. In particular, disclosed are compositions and methods of using the same for the prevention and/or treatment of a loss of any one of muscle mass, muscle strength, muscle function, and physical function, or any combination thereof, for human, and especially adult or animals such as mammals.

BACKGROUND OF THE INVENTION

Large dosages of dietary protein are required to stimulate muscle protein synthesis. The anabolic effects of nutrition are principally driven by the transfer and incorporation of amino acids captured from dietary protein sources, into skeletal muscle proteins. The purpose of this is to compensate for muscle protein that is lost in fasted (post absorptive) periods due to, for example, amino acid oxidation and/or carbon donation for liver gluconeogenesis. However, as humans age the body's ability to digest protein becomes less efficient. Muscle mass loss starts from the age of 30 years at a rate of 3-8 % per decade and accelerates from 60 years of age. This loss reaches up to 35-40 % in elderly over 70, and hence, sarcopenia is especially prominent in elderly. Consequently, age associated progressive loss of muscle mass increases the risks of injury and disability.

Thus, there is a need for a nutritional supplement to expedite rate of muscle protein synthesis to a greater extent that would be expected from consumption of dietary protein.

SUMMARY OF THE INVENTION

An aspect of the present invention provides an amino acid composition comprising the following amino acids; alanine, arginine, asparagine, aspartate, P-alanine, cysteine, citrulline, glutamate, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, ornithine, phenylalanine, proline, serine, taurine, threonine, tryptophan, tyrosine and valine that stimulates muscle protein synthesis more than 50 % at dosages up to 50 grams with or without exercise. Another aspect of the present invention provides a combination comprising an amino acid composition and a P-alanine composition, for simultaneous, separate or sequential administration, wherein the amino acid composition comprises (w/w %): about 3 to 10,5 % of alanine, about 0 to 2 % of arginine, about 0 to 3 % of asparagine, about 0,5 to 5,5 % of aspartate, about 0 to 5 % of cysteine, about 0 to 2 % of citrulline, about 1 to 5 % of glutamate, about 15 to 35 % of glutamine, about 3,5 to 9 % of glycine, about 1 to 4 % of histidine, about 0,5 to 2 % of isoleucine, about 0,5 to 4 % of leucine, about 0,5 to 4,5 % of lysine, about 0,1 to 3 % of methionine, about 0 to 7 % of ornithine, about 0,5 to 3 % of phenylalanine, about 0 to 5 % of proline, about 3 to 15 % of serine, about 25 to 45 % of taurine, about 0,5 to 4 % of threonine, about 0 to 2 % of tryptophan, about 0 to 2 % of tyrosine and about 0,5 to 3 % of valine, and wherein the P-alanine composition comprises about 0.1 to 2 % of P-alanine and is formulated for the sustained release of P-alanine.

Another aspect of the present invention provides a method for stimulating muscle protein synthesis, the method comprising administering to a subject the combination of the invention or a composition comprising the following concentrations of amino acids in terms of w / w % : about 3 to 10,5 % of alanine, about 0 to 2 % of arginine, about 0 to 3 % of asparagine, about 0,5 to 5,5 % of aspartate, about 0 to 2 % of P-alanine, about 0 to 5 % of cysteine, about 0 to 2 % of citrulline, about 1 to 5 % of glutamate, about 15 to 35 % of glutamine, about 3,5 to 9 % of glycine, about 1 to 4 % of histidine, about 0,5 to 2 % of isoleucine, about 0,5 to 4 % of leucine, about 0,5 to 4,5 % of lysine, about 0, 1 to 3 % of methionine, about 0 to 7 % of ornithine, about 0,5 to 3 % of phenylalanine, about 0 to 5 % of proline, about 3 to 15 % of serine, about 25 to 45 % of taurine, about 0,5 to 4 % of threonine, about 0 to 2 % of tryptophan, about 0 to 2 % of tyrosine and about 0,5 to 3 % of valine, wherein stimulating muscle protein synthesis is increased compared to a subject not administered said amino acid composition.

Another aspect of the present invention provides a method for stimulating muscle protein synthesis using a dosage up to 50 grams, the method comprising administering to a subject a composition comprising the following concentrations of amino acids in terms of w / w % : about 3 to 10,5 % of alanine, about 0 to 2 % of arginine, about 0 to 3 % of asparagine, about 0,5 to 5,5 % of aspartate, about 0 to 2 % of P-alanine, about 0 to 5 % of cysteine, about 0 to 2 % of citrulline, about 1 to 5 % of glutamate, about 15 to 35 % of glutamine, about 3,5 to 9 % of glycine, about 1 to 4 % of histidine, about 0,5 to 2 % of isoleucine, about 0,5 to 4 % of leucine, about 0,5 to 4,5 % of lysine, about 0, 1 to 3 % of methionine, about 0 to 7 % of ornithine, about 0,5 to 3 % of phenylalanine, about 0 to 5 % of proline, about 3 to 15 % of serine, about 25 to 45 % of taurine, about 0,5 to 4 % of threonine, about 0 to 2 % of tryptophan, about 0 to 2 % of tyrosine and about 0,5 to 3 % of valine, wherein stimulating muscle protein synthesis is increased relative to a subject not administered said amino acid composition.

Another aspect of the present invention provides a method for reducing muscle fatigue and/or increasing muscle performance in a subject, the method comprising administering to the subject the composition of the invention or the combination of the invention.

Another aspect of the present invention provides a method for improving muscle recovery after exercise in a subject, the method comprising administering to the subject the composition of the invention or the combination of the invention.

DETAILED DESCRIPTION OF THE INVENTION

All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. The publications and applications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. In addition, the materials, methods, and examples are illustrative only and are not intended to be limiting.

In the case of conflict, the present specification, including definitions, will control. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in art to which the subject matter herein belongs. As used herein, the following definitions are supplied in order to facilitate the understanding of the present invention.

The term “comprise” is generally used in the sense of include, that is to say permitting the presence of one or more features or components. Also as used in the specification and claims, the language "comprising" can include analogous embodiments described in terms of "consisting of “ and/or "consisting essentially of’. As used in the specification and claims, the singular form "a", "an" and "the" include plural references unless the context clearly dictates otherwise.

As used in the specification and claims, the term "and/or" used in a phrase such as "A and/or B" herein is intended to include "A and B", "A or B", "A", and "B".

"Effective amount" means a sufficient amount of the specified component / composition to have the specified properties under the specified conditions. For example, an effective amount of a nutritional combination or an amino acids composition means an amount sufficient to cause a desired increase in muscle protein synthesis and/or muscle performance and/or muscle recovery.

The term “ mmol ”, as used herein, is intended to mean millimole. The term " equiv ”, as used herein, is intended to mean equivalent. The term “ mL ”, as used herein, is intended to mean milliliter. The term “ g ”, as used herein, is intended to mean gram. The term “ kg ”, as used herein, is intended to mean kilogram. The term " ug ", as used herein, is intended to mean micrograms. The term “ h ”, as used herein, is intended to mean hour. The term “ min ”, as used herein, is intended to mean minute. The term “ M ”, as used herein, is intended to mean molar. The term “ uL ”, as used herein, is intended to mean microliter. The term “ uM ”, as used herein, is intended to mean micromolar. The term“ nM ”, as used herein, is intended to mean nanomolar. The term “ N ”, as used herein, is intended to mean normal. The term “ amu ”, as used herein, is intended to mean atomic mass unit. The term “ C. ”, as used herein, is intended to mean degree Celsius. The term “ wt / wt ”, as used herein, is intended to mean weight / weight. The term “ v / v ”, as used herein, is intended to mean volume / volume. The term “ MS ”, as used herein, is intended to mean mass spectroscopy. The term “ HPLC ”, as used herein, is intended to mean high performance liquid chromatograph. The term “ RT ”, as used herein, is intended to mean room temperature. The term “ e.g. ”, as used herein, is intended to mean example. The term “ N / A ”, as used herein, is intended to mean not tested.

Numeric ranges recited within this disclosure are inclusive of the numbers defining the range and include each integer within the defined range. Throughout this disclosure, various aspects of this invention are presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible sub - ranges, fractions, and individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed sub - ranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6, and decimals and fractions, for example, 1.2, 3.8, 11/2, and 43/4. This applies regardless of the breadth of the range. In the context of this application, the term “ at least " also includes the starting point of the open range. For example, an amount of at least 95 weight % ” means any amount equal to 95 weight % or above.

The term “ weight percent, ” “ wt- %, ” “ percent by weight, ” “ % by weight, ” and variations thereof, as used herein, refer to the concentration of a substance as the weight of that substance divided by the total weight of the composition and multiplied by 100. It is understood that, as used here, “ percent, ” “ %, " and the like are intended to be synonymous with “ weight percent, ” “ wt- % " etc.

The term “ about, ” as used herein, refers to variation in the numerical quantity that can occur, for example, through typical measuring techniques and equipment, with respect to any quantifiable variable, including, but not limited to, mass and volume. Further, given solid and liquid handling procedures used in the real world, there is certain inadvertent error and variation that is likely through differences in the manufacture, source, or purity of the ingredients used to make the compositions or carry out the methods and the like.

The methods and compositions of the present invention may comprise, consist essentially of, or consist of the components and ingredients of the present invention as well as other ingredients described herein. As used herein, " consisting essentially of " means that the methods and compositions may include additional steps, components or ingredients, but only if the additional steps, components or ingredients do not materially alter the basic and novel characteristics of the claimed methods and compositions.

The disclosure provides, generally, methods, combinations and compositions comprising a specific amino acid formulation capable of stimulating the rate of muscle protein synthesis. Applicants have found the combinations and the compositions as described herein surprisingly stimulate muscle protein synthesis in a highly efficient manner. In particular, the combinations and the compositions as disclosed herein stimulate the production of more muscle protein than the total weight of the components ingested. According to the invention, it was discovered that a formulation containing free specific amino acids (FXAA) in specific amounts, is well suited for stimulation of muscle protein synthesis. In particular, it has been discovered that nutritional combinations and compositions comprising a mixture of (FXAA), effectively stimulate muscle protein synthesis. Advantageously, the combinations and the compositions as disclosed herein were found to be effective in adults where stimulation of muscle protein synthesis, such as skeletal muscle protein, is less efficient. The muscle protein synthesis, such as skeletal muscle protein, is improved relative subjects that did not receive said combinations or compositions and other blends of amino acids on the market and occurs with or without exercise.

Disclosed are the components to be used to prepare the disclosed combinations and compositions as well as the combinations and the compositions themselves to be used within the methods disclosed herein. These and other materials are disclosed herein, and it is understood that when combinations, subsets, interactions, groups, etc. of these materials are disclosed that while specific reference of each various individual and collective combinations and permutation of these compounds may not be explicitly disclosed, each is specifically contemplated and described herein. For example, if a particular compound is disclosed and discussed and a number of modifications that can be made to a number of molecules of the compound are discussed, specifically contemplated is each and every combination and permutation of the compound and the modifications that are possible unless specifically indicated to the contrary. Thus, if a class of molecules A, B, and C are disclosed as well as a class of molecules D, E, and F and an example of a combination molecule, A - D is disclosed, then even if each is not individually recited each is individually and collectively contemplated meaning combinations, A - E, A - F, B - D, B - E, B - F, C - D, C - E, and C - F are considered disclosed. Likewise, any subset or combination of these is also disclosed. Thus, for example, the sub - group of A - E, B - F, and C - E would be considered disclosed. This concept applies to all aspects of this application including, but not limited to, steps in methods of making and using the disclosed compositions. Thus, if there are a variety of additional steps that can be performed it is understood that each of these additional steps can be performed with any specific embodiment or combination of embodiments of the disclosed methods.

Various aspects of the invention are described in further detail in the following sections. An aspect of the present invention provides anabolic amino acid compositions composition useful for the stimulation of muscle protein synthesis, such as skeletal muscle protein. In some embodiments, the composition may comprise the following amino acids: alanine, arginine, asparagine, aspartate, P-alanine, cysteine, citrulline, glutamate, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, ornithine, phenylalanine, proline, serine, taurine, threonine, tryptophan, tyrosine and valine.

Another aspect of the present invention provides an amino acid composition comprising or consisting of the following amino acids; alanine, arginine, asparagine, aspartate, P-alanine, cysteine, citrulline, glutamate, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, ornithine, phenylalanine, proline, serine, taurine, threonine, tryptophan, tyrosine and valine that stimulates muscle protein synthesis more than 50 % at dosages up to 50 grams with or without exercise.

According to some embodiments, the amino acid composition of the invention comprises or consists of the following concentrations of amino acids in terms of w / w % : about 3 to 10,5 % of alanine, about 0 to 2 % of arginine, about 0 to 3 % of asparagine, about 0,5 to 5,5 % of aspartate, about 0 to 2 % of P-alanine, about 0 to 5 % of cysteine, about 0 to 2 % of citrulline, about 1 to 5 % of glutamate, about 15 to 35 % of glutamine, about 3,5 to 9 % of glycine, about 1 to 4 % of histidine, about 0,5 to 2 % of isoleucine, about 0,5 to 4 % of leucine, about 0,5 to 4,5 % of lysine, about 0,1 to 3 % of methionine, about 0 to 7 % of ornithine, about 0,5 to 3 % of phenylalanine, about 0 to 5 % of proline, about 3 to 15 % of serine, about 25 to 45 % of taurine, about 0,5 to 4 % of threonine, about 0 to 2 % of tryptophan, about 0 to 2 % of tyrosine and about 0,5 to 3 % of valine wherein stimulating muscle protein synthesis is increased compared to a subject not administered said amino acid composition.

In some embodiments, the amino acid composition comprises or consists of the following amino acids: alanine, arginine, asparagine, aspartate, P-alanine, cysteine, citrulline, glutamate, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, ornithine, phenylalanine, proline, serine, taurine, threonine, tryptophan, tyrosine and valine.

In other embodiments, the amino acid composition of the invention comprises or consists of the following concentrations of amino acids in terms of w / w % : about 3 to 10,5 % of alanine, about 0 to 2 % of arginine, about 0 to 3 % of asparagine, about 0,5 to 5,5 % of aspartate, about 0 to 2 % of P-alanine, about 0 to 5 % of cysteine, about 0 to 2 % of citrulline, about 1 to 5 % of glutamate, about 15 to 35 % of glutamine, about 3,5 to 9 % of glycine, about 1 to 4 % of histidine, about 0,5 to 2 % of isoleucine, about 0,5 to 4 % of leucine, about 0,5 to 4,5 % of lysine, about 0,1 to 3 % of methionine, about 0 to 7 % of ornithine, about 0,5 to 3 % of phenylalanine, about 0 to 5 % of proline, about 3 to 15 % of serine, about 25 to 45 % of taurine, about 0,5 to 4 % of threonine, about 0 to 2 % of tryptophan, about 0 to 2 % of tyrosine and about 0,5 to 3 % of valine.

In some preferred embodiments, the amino acid composition of the invention comprises or consists of the following concentrations of amino acids in terms of w / w % : 5,20 % of alanine, 0,9 % of arginine, 1,6 % of asparagine, 2,8 % of aspartate, 0,55 % of P-alanine, 0,9 % of citrulline, 2,4 % of glutamate, 23,65 % of glutamine, 4,55 % of glycine, 2,15 % of histidine, 1 % of isoleucine, 1,9 % of leucine, 2,3 % of lysine, 0,4 % of methionine, 3,55 % of ornithine, 0,8 % of phenylalanine, 7,65 % of serine, 33,45 % of taurine, 2 % of threonine, 1,15 % of tyrosine and 1,1 % of valine.

Regarding some regulations, P-alanine must be taken separately with a controlled and/or sustained released rate.

Another aspect of the present invention provides a combination comprising or consisting of an amino acid composition and a P-alanine composition, for simultaneous, separate or sequential administration, wherein the amino acid composition comprises or consists of (w/w %): about 3 to 10,5 % of alanine, about 0 to 2 % of arginine, about 0 to 3 % of asparagine, about 0,5 to 5,5 % of aspartate, about 0 to 5 % of cysteine, about 0 to 2 % of citrulline, about 1 to 5 % of glutamate, about 15 to 35 % of glutamine, about 3,5 to 9 % of glycine, about 1 to 4 % of histidine, about 0,5 to 2 % of isoleucine, about 0,5 to 4 % of leucine, about 0,5 to 4,5 % of lysine, about 0,1 to 3 % of methionine, about 0 to 7 % of ornithine, about 0,5 to 3 % of phenylalanine, about 0 to 5 % of proline, about 3 to 15 % of serine, about 25 to 45 % of taurine, about 0,5 to 4 % of threonine, about 0 to 2 % of tryptophan, about 0 to 2 % of tyrosine and about 0,5 to 3 % of valine, and wherein the P-alanine composition comprises or consists of about 0.001 to 2%, preferably 0.1 to 2 %, of P-alanine and is formulated for the sustained release of P-alanine. The administration of the combination of the invention encompasses co-administration of the amino acid composition and the P-alanine composition in a substantially simultaneous manner, such as in separate formulations for each composition. In addition, such administration also encompasses administration of each composition in a sequential or separate manner, either at approximately the same time or at different times. Regardless of whether the compositions are administered simultaneously, separately or sequentially, the compositions are administered to the same subject as part of the same course of dietary, food or nutraceutical supplementation.

The combination of the invention can be a dietary combination, a dietary supplement combination, a food supplement combination or a nutritional combination. Preferably, the combination of the invention is a dietary supplement combination.

According to some embodiments of the combination of the invention, the preferred P-alanine compositions comprising P-alanine, such as free P-alanine or a biological source thereof, are sustained release formulations. According to some other embodiments of the combination of the invention, the preferred P-alanine compositions consist essentially of P-alanine, such as free P-alanine or a biological source thereof, and of usual carriers, binders, excipients, additives and/or coating agents for a sustained release formulation.

For the purposes of the present invention, the following terms may be considered to be substantially equivalent to "sustained release": continuous release, controlled release, delayed release, depot, gradual release, long-term release, programmed release, prolonged release, proportionate release, protracted release, repository, retard, slow release, spaced release, time coat, timed release, delayed action, extended action, layered-time action, long-acting, prolonged action, repeated action, slowing acting, sustained action, sustained-action medications, and extended release. Further discussions of these terms may be found in Lesczek Krowczynski, Extended-Release Dosage Forms, 1987 (CRC Press, Inc.).

According to some further embodiments, the amino acid compositions of the invention and/or the combinations of the invention further comprise a grape seed extract. Indeed, the combination of the amino acid composition of the invention with a grape seed extract provides a synergistic effect on muscle protein synthesis, on muscle recovery, on increasing muscle performance and/or on reducing muscle fatigue. The "grape seed extract" refer to any compound or combination of compounds obtained from grape seed (i.e., polyphenols, catechins, procyanidins, flavonols, oligomeric proanthocyanidins, polymeric proanthocyanidins, gallic acid esters, etc.) and/or to any oils obtained from grape seed, as well as to chemical derivatives thereof. The grape seed extract used in the present invention may be obtained from commercially available sources. Additionally, there are numerous extraction methods that can be used to produce a grape seed extract suitable for use in the present invention. These extraction methods are well-known in the art, and may be described in various publications and patents. For example, a grape seed extract is made from the crushed seeds of (wine) grape plants. Typically, a grape seed extract contains proanthocyanidin. This is a phenolic chemical belonging in the larger group of plant phytochemicals called flavonoids. It belongs to a subgroup of tannins.

In general, the amino acids may be L - amino acids, D - amino acids or mixtures thereof. In preferred embodiments, the amino acids are L - amino acids. Those of skill in the art will appreciate that the amino acids of the composition may be free amino acids or amino acids salts. The amino acid composition of the invention may also be in the form of intact protein or peptide, provided that the protein or peptide comprises the amino acids of the invention in the correct concentrations relative to each other. In preferred embodiments, the amino acids of the invention are free amino acids or amino acids salts. If not obtained commercially, individual amino acids may be produced by processes well known in the art, including chemical synthesis or use of recombinant microorganisms.

The amino acids may be the canonical amino acids alanine, arginine, asparagine, aspartate, P- alanine, cysteine, citrulline, glutamate, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, ornithine, phenylalanine, proline, serine, taurine, threonine, tryptophan, tyrosine and valine, or non-canonical amino acid derivatives ( e.g. a precursor to an amino acid ). Nonlimiting examples of non-canonical amino acids that may be used in the invention include L - lysine acetate, derivatives of L - tyrosine, ornithine, keto acid analogs, hydrochloride salt ( L - cysteine HCL.H, O ), and N - acetyl derivatives of the various amino acids. In preferred embodiments, the amino acids used in the compositions and solutions of the present invention may be in free form or salt form.

In one aspect, a combination of the disclosure and an amino acid composition of the disclosure comprises one or more essential amino acids. An essential amino acid (EAA) is an amino acid that cannot be synthesized de novo by a subject, and therefore must be supplied in its diet. The amino acids regarded as essential for humans are phenylalanine, valine, threonine, tryptophan, methionine, leucine, isoleucine, lysine, and histidine. In some embodiments, a combination of at least five of the EAA comprises phenylalanine, valine, threonine, tryptophan, methionine, leucine, isoleucine, lysine, and histidine. In preferred embodiments, the combination of amino acid composition also comprises at least ten conditionally essential amino acid.

The amino acids alanine, arginine, asparagine, aspartate, P-alanine, cysteine, citrulline, glutamate, glutamine, glycine, ornithine, proline, serine, taurine and tyrosine are considered conditionally essential, meaning they are not normally required in the diet, but must be supplied exogenously to specific populations that do not synthesize them in adequate amounts. For example, the body produces sufficient arginine to satisfy metabolic requirements under normal conditions. Therefore, arginine supplementation is not necessary to stimulate muscle protein synthesis for many subjects. However, in certain clinical circumstances, including in elderly with heart failure, endogenous arginine production is inadequate to meet all demands. For such a population, it is advantageous for combinations of the invention to comprise arginine, or a precursor of the amino acid arginine. The term “ amino acid precursor ” refers to a metabolic precursor of an amino acid. For example, serine is a metabolic precursor of cysteine and glycine; and 3 - phosphoglycerate is a metabolic precursor of serine and, therefore, of cysteine and glycine too. As a second example, citrulline is a metabolic precursor of arginine. The metabolic pathways that synthesize amino acids are well known in the art, and a skilled artisan may refer to these to identify metabolic precursors of other amino acids. In some embodiments, a combination of the invention comprises at least five of the EAA phenylalanine, valine, threonine, tryptophan, methionine, leucine, isoleucine, lysine, histidine, and at least ten conditionally essential amino acid of the following list alanine, arginine, asparagine, aspartate, P-alanine, cysteine, citrulline, glutamate, glutamine, glycine, ornithine, proline, serine, taurine and tyrosine. For example, the combination may comprise 10, 11, 12, 13, 14 or 15 conditionally essential amino acids. In other embodiments, a combination of the invention comprises at least five of the EAA phenylalanine, valine, threonine, tryptophan, methionine, leucine, isoleucine, lysine, histidine, and at least ten conditionally essential amino acid precursor. For example, the combination may comprise 10, 11, 12, 13, 14 or 15 conditionally essential amino acid precursors. In still other embodiments, a combination of the invention comprises at least five of the EAA phenylalanine, valine, threonine, tryptophan, methionine, leucine, isoleucine, lysine, histidine, at least ten non - essential amino acid or conditionally essential amino acid precursor.

In some embodiments, the composition may comprise the following concentrations of alanine in terms of w / w % : about 3 % to about 10,5 %, about 3,1 % to about 10,5 %, about 3,2 % to about 10,5 %, about 3,3 % to about 10,5 %, about 3,4 % to about 10,5 %, about 3,5 % to about

10,5 %, about 3,6 % to about 10,5 %, about 3,7 % to about 10,5 %, about 3,8 % to about 10,5 %, about 3,9 % to about 10,5 %, about 4 % to about 10,5 %, about 4,1 % to about 10,5 %, about 4,2 % to about 10,5 %, about 4,3 % to about 10,5 %, about 4,4 % to about 10,5 %, about 4,5 % to about 10,5 %, about 4,6 % to about 10,5 %, about 4,7 % to about 10,5 %, about 4,8 % to about 10,5 %, about 4,9 % to about 10,5 %, about 5 % to about 10,5 %, about 5,1 % to about

10,5 %, about 5,2 % to about 10,5 %, about 5,3 % to about 10,5 %, about 5,4 % to about 10,5 %, about 5,5 % to about 10,5 %, about 5,6 % to about 10,5 %, about 5,7 % to about 10,5 %, about 5,8 % to about 10,5 %, about 5,9 % to about 10,5 %, about 6 % to about 10,5 %, about 6,1 % to about 10,5 %, about 6,2 % to about 10,5 %, about 6,3 % to about 10,5 %, about 6,4 % to about 10,5 %, about 6,5 % to about 10,5 %, about 6,6 % to about 10,5 %, about 6,7 % to about 10,5 %, about 6,8 % to about 10,5 %, about 6,9 % to about 10,5 %, about 7 % to about

10,5 %, about 7,1 % to about 10,5 %, about 7,2 % to about 10,5 %, about 7,3 % to about 10,5 %, about 7,4 % to about 10,5 %, about 7,5 % to about 10,5 %, about 7,6 % to about 10,5 %, about 7,7 % to about 10,5 %, about 7,8 % to about 10,5 %, about 7,9 % to about 10,5 %, about 8 % to about 10,5 %, about 8,1 % to about 10,5 %, about 8,2 % to about 10,5 %, about 8,3 % to about 10,5 %, about 8,4 % to about 10,5 %, about 8,5 % to about 10,5 %, about 8,6 % to about 10,5 %, about 8,7 % to about 10,5 %, about 8,8 % to about 10,5 %, about 8,9 % to about

10,5 %, about 9 % to about 10,5 %, about 9,1 % to about 10,5 %, about 9,2 % to about 10,5 %, about 9,3 % to about 10,5 %, about 9,4 % to about 10,5 %, about 9,5 % to about 10,5 %, about 9,6 % to about 10,5 %, about 9,7 % to about 10,5 %, about 9,8 % to about 10,5 %, about 9,9 % to about 10,5 %, about 10 % to about 10,5 %, about 10,1 % to about 10,5 %, about 10,2 % to about 10,5 %, about 10,3 % to about 10,5 %, about 10,4 % to about 10,5 % of alanine.

In some embodiments, the composition may comprise the following concentrations of arginine in terms of w / w % : about 0 % to about 2 %, about 0, 1 % to about 2 %, about 0,2 % to about 2 %, about 0,3 % to about 2 %, about 0,4 % to about 2 %, about 0,5 % to about 2 %, about 0,6 % to about 2 %, about 0,7 % to about 2 %, about 0,8 % to about 2 %, about 0,9 % to about 2 %, about 1 % to about 2 %, about 1,1 % to about 2 %, about 1,2 % to about 2 %, about 1,3 % to about 2 %, about 1,4 % to about 2 %, about 1,5 % to about 2 %, about 1,6 % to about 2 %, about 1,7 % to about 2 %, about 1,8 % to about 2 %, about 1,9 % to about 2 % of arginine.

In some embodiments, the composition may comprise the following concentrations of asparagine in terms of w / w % : about 0 % to about 3 %, about 0,1 % to about 3 %, about 0,2 % to about 3 %, about 0,3 % to about 3 %, about 0,4 % to about 3 %, about 0,5 % to about 3 %, about 0,6 % to about 3 %, about 0,7 % to about 3 %, about 0,8 % to about 3 %, about 0,9 % to about 3 %, about 1 % to about 3 %, about 1,1 % to about 3 %, about 1,2 % to about 3 %, about 1,3 % to about 3 %, about 1,4 % to about 3 %, about 1,5 % to about 3 %, about 1,6 % to about 3 %, about 1,7 % to about 3 %, about 1,8 % to about 3 %, about 1,9 % to about 3 %, about 2 % to about 3 %, about 2,1 % to about 3 %, about 2,2 % to about 3 %, about 2,3 % to about 3 %, about 2,4 % to about 3 %, about 2,5 % to about 3 %, about 2,6 % to about 3 %, about 2,7 % to about 3 %, about 2,8 % to about 3 %, about 2,9 % to about 3 % of asparagine.

In some embodiments, the composition may comprise the following concentrations of aspartate in terms of w / w % : about 0,5 % to about 5,5 %, about 0,6 % to about 5,5 %, about 0,7 % to about 5,5 %, about 0,8 % to about 5,5 %, about 0,9 % to about 5,5 %, about 1 % to about 5,5 %, about 1,1 % to about 5,5 %, about 1,2 % to about 5,5 %, about 1,3 % to about 5,5 %, about

1.4 % to about 5,5 %, about 1,5 % to about 5,5 %, about 1,6 % to about 5,5 %, about 1,7 % to about 5,5 %, about 1,8 % to about 5,5 %, about 1,9 % to about 5,5 %, about 2 % to about 5,5 %, about 2,1 % to about 5,5 %, about 2,2 % to about 5,5 %, about 2,3 % to about 5,5 %, about

2.4 % to about 5,5 %, about 2,5 % to about 5,5 %, about 2,6 % to about 5,5 %, about 2,7 % to about 5,5 %, about 2,8 % to about 5,5 %, about 2,9 % to about 5,5 %, about 3 % to about 5,5 %, about 3,1 % to about 5,5 %, about 3,2 % to about 5,5 %, about 3,3 % to about 5,5 %, about

3.4 % to about 5,5 %, about 3,5 % to about 5,5 %, about 3,6 % to about 5,5 %, about 3,7 % to about 5,5 %, about 3,8 % to about 5,5 %, about 3,9 % to about 5,5 %, about 4 % to about 5,5 %, about 4,1 % to about 5,5 %, about 4,1 % to about 5,5 %, about 4,2 % to about 5,5 %, about

4.3 % to about 5,5 %, about 4,4 % to about 5,5 %, about 4,5 % to about 5,5 %, about 4,6 % to about 5,5 %, about 4,7 % to about 5,5 %, about 4,8 % to about 5,5 %, about 4,9 % to about 5,5 %, about 5 % to about 5,5 %, about 5,1 % to about 5,5 %, about 5,2 % to about 5,5 %, about

5.3 % to about 5,5 %, about 5,4 % to about 5,5 % of aspartate.

In some embodiments, the composition and/or the P-alanine composition may comprise the following concentrations of P-alanine in terms of w / w % : about 0 % to about 2 %, about 0.001 % to 2 %, about 0,1 % to about 2 %, about 0,2 % to about 2 %, about 0,3 % to about 2 %, about 0,4 % to about 2 %, about 0,5 % to about 2 %, about 0,6 % to about 2 %, about 0,7 % to about 2 %, about 0,8 % to about 2 %, about 0,9 % to about 2 %, about 1 % to about 2 %, about 1,1 % to about 2 %, about 1,2 % to about 2 %, about 1,3 % to about 2 %, about 1,4 % to about 2 %, about 1,5 % to about 2 %, about 1,6 % to about 2 %, about 1,7 % to about 2 %, about 1,8 % to about 2 %, about 1,9 % to about 2 % of P-alanine.

In some embodiments, the composition may comprise the following concentrations of cysteine in terms of w / w % : about 0 % to about 5 %, about 0,1 % to about 5 %, about 0,2 % to about 5 %, about 0,3 % to about 5 %, about 0,4 % to about 5 %, about 0,5 % to about 5 %, about 0,6 % to about 5 %, about 0,7 % to about 5 %, about 0,8 % to about 5 %, about 0,9 % to about 5 %, about 1 % to about 5 %, about 1,1 % to about 5 %, about 1,2 % to about 5 %, about 1,3 % to about 5 %, about 1,4 % to about 5 %, about 1,5 % to about 5 %, about 1,6 % to about 5 %, about 1,7 % to about 5 %, about 1,8 % to about 5 %, about 1,9 % to about 5 %, about 2 % to about 5 %, about 2,1 % to about 5 %, about 2,2 % to about 5 %, about 2,3 % to about 5 %, about 2,4 % to about 5 %, about 2,5 % to about 5 %, about 2,6 % to about 5 %, about 2,7 % to about 5 %, about 2,8 % to about 5 %, about 2,9 % to about 5 %, about 3 % to about 5 %, about 3,1 % to about 5 %, about 3,2 % to about 5 %, about 3,3 % to about 5 %, about 3,4 % to about 5 %, about 3,5 % to about 5 %, about 3,6 % to about 5 %, about 3,7 % to about 5 %, about 3,8 % to about 5 %, about 3,9 % to about 5 %, about 4 % to about 5 %, about 4,1 % to about 5 %, about 4,1 % to about 5 %, about 4,2 % to about 5 %, about 4,3 % to about 5 %, about 4,4 % to about 5 %, about 4,5 % to about 5 %, about 4,6 % to about 5 %, about 4,7 % to about 5 %, about 4,8 % to about 5 %, about 4,9 % to about 5 % of cysteine.

In some embodiments, the composition may comprise the following concentrations of citrulline in terms of w / w % : about 0 % to about 2 %, about 0,1 % to about 2 %, about 0,2 % to about 2 %, about 0,3 % to about 2 %, about 0,4 % to about 2 %, about 0,5 % to about 2 %, about 0,6 % to about 2 %, about 0,7 % to about 2 %, about 0,8 % to about 2 %, about 0,9 % to about 2 %, about 1 % to about 2 %, about 1,1 % to about 2 %, about 1,2 % to about 2 %, about 1,3 % to about 2 %, about 1,4 % to about 2 %, about 1,5 % to about 2 %, about 1,6 % to about 2 %, about 1,7 % to about 2 %, about 1,8 % to about 2 %, about 1,9 % to about 2 % of citrulline.

In some embodiments, the composition may comprise the following concentrations of glutamate in terms of w / w % : about 1 % to about 5 %, about 1,1 % to about 5 %, about 1,2 % to about 5 %, about 1,3 % to about 5 %, about 1,4 % to about 5 %, about 1,5 % to about 5 %, about 1,6 % to about 5 %, about 1,7 % to about 5 %, about 1,8 % to about 5 %, about 1,9 % to about 5 %, about 2 % to about 5 %, about 2, 1 % to about 5 %, about 2,2 % to about 5 %, about 2,3 % to about 5 %, about 2,4 % to about 5 %, about 2,5 % to about 5 %, about 2,6 % to about 5 %, about 2,7 % to about 5 %, about 2,8 % to about 5 %, about 2,9 % to about 5 %, about 3 % to about 5 %, about 3,1 % to about 5 %, about 3,2 % to about 5 %, about 3,3 % to about 5 %, about 3,4 % to about 5 %, about 3,5 % to about 5 %, about 3,6 % to about 5 %, about 3,7 % to about 5 %, about 3,8 % to about 5 %, about 3,9 % to about 5 %, about 4 % to about 5 %, about 4,1 % to about 5 %, about 4,1 % to about 5 %, about 4,2 % to about 5 %, about 4,3 % to about 5 %, about 4,4 % to about 5 %, about 4,5 % to about 5 %, about 4,6 % to about 5 %, about 4,7 % to about 5 %, about 4,8 % to about 5 %, about 4,9 % to about 5 % of glutamate.

In some embodiments, the composition may comprise the following concentrations of glutamine in terms of w / w % : about 15 % to about 35 %, about 15,1 % to about 35 %, about 15,2 % to about 35 %, about 15,3 % to about 35 %, about 15,4 % to about 35 %, about 15,5 % to about 35 %, about 15,6 % to about 35 %, about 15,7 % to about 35 %, about 15,8 % to about 35 %, about 15,9 % to about 35 %, about 16 % to about 35 %, about 16,1 % to about 35 %, about 16,2 % to about 35 %, about 16,3 % to about 35 %, about 16,4 % to about 35 %, about 16,5 % to about 35 %, about 16,6 % to about 35 %, about 16,7 % to about 35 %, about 16,8 % to about 35 %, about 16,9 % to about 35 %, about 17% to about 35 %, about 17,1 % to about 35 %, about 17,2 % to about 35 %, about 17,3 % to about 35 %, about 17,4 % to about 35 %, about 17,5 % to about 35 %, about 17,6 % to about 35 %, about 17,7 % to about 35 %, about 17,8 % to about 35 %, about 17,9 % to about 35 %, about 18 % to about 35 %, about 18,1 % to about 35 %, about 18,2 % to about 35 %, about 18,3 % to about 35 %, about 18,4 % to about 35 %, about 18,5 % to about 35 %, about 18,6 % to about 35 %, about 18,7 % to about 35 %, about 18,8 % to about 35 %, about 18,9 % to about 35 %, about 19 % to about 35 %, about 19,1 % to about 35 %, about 19,2 % to about 35 %, about 19,3 % to about 35 %, about 19,4 % to about 35 %, about 19,5 % to about 35 %, about 19,6 % to about 35 %, about 19,7 % to about 35 %, about 19,8 % to about 35 %, about 19,9 % to about 35 %, about 20 % to about 35 %, about 20,1 % to about 35 %, about 20,2 % to about 35 %, about 20,3 % to about 35 %, about 20,4 % to about 35 %, about 20,5 % to about 35 %, about 20,6 % to about 35 %, about 20,7 % to about 35 %, about 20,8 % to about 35 %, about 20,9 % to about 35 %, about 21 % to about 35 %, about 21,1 % to about 35 %, about 21,2 % to about 35 %, about 21,3 % to about 35 %, about 21,4 % to about 35 %, about 21,5 % to about 35 %, about 21,6 % to about 35 %, about

21.7 % to about 35 %, about 21,8 % to about 35 %, about 21,9 % to about 35 %, about 22 % to about 35 %, about 22,1 % to about 35 %, about 22,2 % to about 35 %, about 22,3 % to about 35 %, about 22,4 % to about 35 %, about 22,5 % to about 35 %, about 22,6 % to about 35 %, about 22,7 % to about 35 %, about 22,8 % to about 35 %, about 22,9 % to about 35 %, about 23 % to about 35 %, about 23,1 % to about 35 %, about 23,2 % to about 35 %, about 23,3 % to about 35 %, about 23,4 % to about 35 %, about 23,5 % to about 35 %, about 23,6 % to about 35 %, about 23,7 % to about 35 %, about 23,8 % to about 35 %, about 23,9 % to about 35 %, about 24 % to about 35 %, about 24,1 % to about 35 %, about 24,2 % to about 35 %, about 24,3 % to about 35 %, about 24,4 % to about 35 %, about 24,5 % to about 35 %, about 24,6 % to about 35 %, about 24,7 % to about 35 %, about 24,8 % to about 35 %, about 24,9 % to about 35 %, about 25 % to about 35 %, about 25,1 % to about 35 %, about 25,2 % to about 35 %, about 25,3 % to about 35 %, about 25,4 % to about 35 %, about 25,5 % to about 35 %, about 25,6 % to about 35 %, about 25,7 % to about 35 %, about 25,8 % to about 35 %, about 25,9 % to about 35 %, about 26 % to about 35 %, about 26,1 % to about 35 %, about 26,2 % to about 35 %, about 26,3 % to about 35 %, about 26,4 % to about 35 %, about 26,5 % to about 35 %, about 26,6 % to about 35 %, about 26,7 % to about 35 %, about 26,8 % to about 35 %, about 26,9 % to about 35 %, about 27 % to about 35 %, about 27,1 % to about 35 %, about 27,2 % to about 35 %, about 27,3 % to about 35 %, about 27,4 % to about 35 %, about 27,5 % to about 35 %, about 27,6 % to about 35 %, about 27,7 % to about 35 %, about 27,8 % to about 35 %, about 27,9 % to about 35 %, about 28 % to about 35 %, about 28,1 % to about 35 %, about 28,2 % to about 35 %, about 28,3 % to about 35 %, about 28,4 % to about 35 %, about 28,5 % to about 35 %, about 28,6 % to about 35 %, about 28,7 % to about 35 %, about 28,8 % to about 35 %, about 28,9 % to about 35 %, about 29 % to about 35 %, about 29,1 % to about 35 %, about 29,2 % to about 35 %, about 29,3 % to about 35 %, about 29,4 % to about 35 %, about 29,5 % to about 35 %, about 29,6 % to about 35 %, about 29,7 % to about 35 %, about 29,8 % to about 35 %, about 29,9 % to about 35 %, about 30 % to about 35 %, about 30,1 % to about 35 %, about 30,2 % to about 35 %, about 30,3 % to about 35 %, about 30,4 % to about 35 %, about 30,5 % to about 35 %, about 30,6 % to about 35 %, about 30,7 % to about 35 %, about

30.8 % to about 35 %, about 30,9 % to about 35 %, about 31 % to about 35 %, about 31,1 % to about 35 %, about 31,2 % to about 35 %, about 31,3 % to about 35 %, about 31,4 % to about 35 %, about 31,5 % to about 35 %, about 31,6 % to about 35 %, about 31,7 % to about 35 %, about 31,8 % to about 35 %, about 31,9 % to about 35 %, about 32 % to about 35 %, about 32,1 % to about 35 %, about 32,2 % to about 35 %, about 32,3 % to about 35 %, about 32,4 % to about 35 %, about 32,5 % to about 35 %, about 32,6 % to about 35 %, about 32,7 % to about 35 %, about 32,8 % to about 35 %, about 32,9 % to about 35 %, about 33 % to about 35 %, about 33,1 % to about 35 %, about 33,2 % to about 35 %, about 33,3 % to about 35 %, about 33,4 % to about 35 %, about 33,5 % to about 35 %, about 33,6 % to about 35 %, about 33,7 % to about 35 %, about 33,8 % to about 35 %, about 33,9 % to about 35 %, about 34 % to about 35 %, about 34,1 % to about 35 %, about 34,2 % to about 35 %, about 34,3 % to about 35 %, about 34,4 % to about 35 %, about 34,5 % to about 35 %, about 34,6 % to about 35 %, about 34,7 % to about 35 %, about 34,8 % to about 35 %, about 34,9 % to about 35 % of glutamine.

In some embodiments, the composition may comprise the following concentrations of glycine in terms of w / w % : about 3,5 % to about 9 %, about 3,6 % to about 9 %, about 3,7 % to about 9 %, about 3,8 % to about 9 %, about 3,9 % to about 9 %, about 4 % to about 9 %, about 4, 1 % to about 9 %, about 4,2 % to about 9 %, about 4,3 % to about 9 %, about 4,4 % to about 9 %, about 4,5 % to about 9 %, about 4,6 % to about 9 %, about 4,7 % to about 9 %, about 4,8 % to about 9 %, about 4,9 % to about 9 %, about 5 % to about 9 %, about 5,1 % to about 9 %, about 5,2 % to about 9 %, about 5,3 % to about 9 %, about 5,4 % to about 9 %, about 5,5 % to about 9 %, about 5,6 % to about 9 %, about 5,7 % to about 9 %, about 5,8 % to about 9 %, about 5,9 % to about 9 %, about 6 % to about 9 %, about 6,1 % to about 9 %, about 6,2 % to about 9 %, about 6,3 % to about 9 %, about 6,4 % to about 9 %, about 6,5 % to about 9 %, about 6,6 % to about 9 %, about 6,7 % to about 9 %, about 6,8 % to about 9 %, about 6,9 % to about 9 %, about 7 % to about 9 %, about 7,1 % to about 9 %, about 7,2 % to about 9 %, about 7,3 % to about 9 %, about 7,4 % to about 9 %, about 7,5 % to about 9 %, about 7,6 % to about 9 %, about 7,7 % to about 9 %, about 7,8 % to about 9 %, about 7,9 % to about 9 %, about 8 % to about 9 %, about 8,1 % to about 9 %, about 8,2 % to about 9 %, about 8,3 % to about 9 %, about 8,4 % to about 9 %, about 8,5 % to about 9 %, about 8,6 % to about 9 %, about 8,7 % to about 9 %, about 8,8 % to about 9 %, about 8,9 % to about 9 % of glycine.

In some embodiments, the composition may comprise the following concentrations of histidine in terms of w / w % : about 1 % to about 4 %, about 1,1 % to about 4 %, about 1,2 % to about 4 %, about 1,3 % to about 4 %, about 1,4 % to about 4 %, about 1,5 % to about 4 %, about 1,6 % to about 4 %, about 1,7 % to about 4 %, about 1,8 % to about 4 %, about 1,9 % to about 4 %, about 2 % to about 4 %, about 2, 1 % to about 4 %, about 2,2 % to about 4 %, about 2,3 % to about 4 %, about 2,4 % to about 4 %, about 2,5 % to about 4 %, about 2,6 % to about 4 %, about 2,7 % to about 4 %, about 2,8 % to about 4 %, about 2,9 % to about 4 %, about 3 % to about 4 %, about 3,1 % to about 4 %, about 3,2 % to about 4 %, about 3,3 % to about 4 %, about 3,4 % to about 4 %, about 3,5 % to about 4 %, about 3,6 % to about 4 %, about 3,7 % to about 4 %, about 3,8 % to about 4 %, about 3,9 % to about 4 % of histidine.

In some embodiments, the composition may comprise the following concentrations of isoleucine in terms of w / w % : about 0,5 % to about 2 %, about 0,6 % to about 2 %, about 0,7

% to about 2 %, about 0,8 % to about 2 %, about 0,9 % to about 2 %, about 1 % to about 2 %, about 1,1 % to about 2 %, about 1,2 % to about 2 %, about 1,3 % to about 2 %, about 1,4 % to about 2 %, about 1,5 % to about 2 %, about 1,6 % to about 2 %, about 1,7 % to about 2 %, about 1,8 % to about 2 %, about 1,9 % to about 2 % of isoleucine.

In some embodiments, the composition may comprise the following concentrations of leucine in terms of w / w % : about 0,5 % to about 4 %, about 0,6 % to about 4 %, about 0,7 % to about 4 %, about 0,8 % to about 4 %, about 0,9 % to about 4 %, about 1 % to about 4 %, about 1,1 % to about 4 %, about 1,2 % to about 4 %, about 1,3 % to about 4 %, about 1,4 % to about 4 %, about 1,5 % to about 4 %, about 1,6 % to about 4 %, about 1,7 % to about 4 %, about 1,8 % to about 4 %, about 1,9 % to about 4 %, about 2 % to about 4 %, about 2,1 % to about 4 %, about 2,2 % to about 4 %, about 2,3 % to about 4 %, about 2,4 % to about 4 %, about 2,5 % to about 4 %, about 2,6 % to about 4 %, about 2,7 % to about 4 %, about 2,8 % to about 4 %, about 2,9 % to about 4 %, about 3 % to about 4 %, about 3,1 % to about 4 %, about 3,2 % to about 4 %, about 3,3 % to about 4 %, about 3,4 % to about 4 %, about 3,5 % to about 4 %, about 3,6 % to about 4 %, about 3,7 % to about 4 %, about 3,8 % to about 4 %, about 3,9 % to about 4 of leucine.

In some embodiments, the composition may comprise the following concentrations of lysine in terms of w / w % : about 0,5 % to about 4,5 %, about 0,6 % to about 4,5 %, about 0,7 % to about 4,5 %, about 0,8 % to about 4,5 %, about 0,9 % to about 4,5 %, about 1 % to about 4,5 %, about 1,1 % to about 4,5 %, about 1,2 % to about 4,5 %, about 1,3 % to about 4,5 %, about

1.4 % to about 4,5 %, about 1,5 % to about 4,5 %, about 1,6 % to about 4,5 %, about 1,7 % to about 4,5 %, about 1,8 % to about 4,5 %, about 1,9 % to about 4,5 %, about 2 % to about 4,5 %, about 2,1 % to about 4,5 %, about 2,2 % to about 4,5 %, about 2,3 % to about 4,5 %, about

2.4 % to about 4,5 %, about 2,5 % to about 4,5 %, about 2,6 % to about 4,5 %, about 2,7 % to about 4,5 %, about 2,8 % to about 4,5 %, about 2,9 % to about 4,5 %, about 3 % to about 4,5 %, about 3,1 % to about 4,5 %, about 3,2 % to about 4,5 %, about 3,3 % to about 4,5 %, about 3,4 % to about 4,5 %, about 3,5 % to about 4,5 %, about 3,6 % to about 4,5 %, about 3,7 % to about 4,5 %, about 3,8 % to about 4,5 %, about 3,9 % to about 4,5 %, about 4 % to about 4,5

%, about 4,1 % to about 4,5 %, about 4,1 % to about 4,5 %, about 4,2 % to about 4,5 %, about

4,3 % to about 4,5 %, about 4,4 % to about 4,5 % of lysine.

In some embodiments, the composition may comprise the following concentrations of methionine in terms of w / w % : about 0,1 % to about 3 %, about 0,2 % to about 3 %, about 0,3 % to about 3 %, about 0,4 % to about 3 %, about 0,5 % to about 3 %, about 0,6 % to about 3 %, about 0,7 % to about 3 %, about 0,8 % to about 3 %, about 0,9 % to about 3 %, about 1 % to about 3 %, about 1,1 % to about 3 %, about 1,2 % to about 3 %, about 1,3 % to about 3 %, about 1,4 % to about 3 %, about 1,5 % to about 3 %, about 1,6 % to about 3 %, about 1,7 % to about 3 %, about 1,8 % to about 3 %, about 1,9 % to about 3 %, about 2 % to about 3 %, about 2,1 % to about 3 %, about 2,2 % to about 3 %, about 2,3 % to about 3 %, about 2,4 % to about 3 %, about 2,5 % to about 3 %, about 2,6 % to about 3 %, about 2,7 % to about 3 %, about 2,8 % to about 3 %, about 2,9 % to about 3 % of methionine.

In some embodiments, the composition may comprise the following concentrations of ornithine in terms of w / w % : about 0 % to about 7 %, about 0,1 % to about 7 %, about 0,2 % to about 7 %, about 0,3 % to about 7 %, about 0,4 % to about 7 %, about 0,5 % to about 7 %, about 0,6 % to about 7 %, about 0,7 % to about 7 %, about 0,8 % to about 7 %, about 0,9 % to about 7 %, about 1 % to about 7 %, about 1,1 % to about 7 %, about 1,2 % to about 7 %, about 1,3 % to about 7 %, about 1,4 % to about 7 %, about 1,5 % to about 7 %, about 1,6 % to about 7 %, about 1,7 % to about 7 %, about 1,8 % to about 7 %, about 1,9 % to about 7 %, about 2 % to about 7 %, about 2,1 % to about 7 %, about 2,2 % to about 7 %, about 2,3 % to about 7 %, about 2,4 % to about 7 %, about 2,5 % to about 7 %, about 2,6 % to about 7 %, about 2,7 % to about 7 %, about 2,8 % to about 7 %, about 2,9 % to about 7 %, about 3 % to about 7 %, about 3,1 % to about 7 %, about 3,2 % to about 7 %, about 3,3 % to about 7 %, about 3,4 % to about 7 %, about 3,5 % to about 7 %, about 3,6 % to about 7 %, about 3,7 % to about 7 %, about 3,8 % to about 7 %, about 3,9 % to about 7 %, about 4 % to about 7 %, about 4,1 % to about 7 %, about 4,2 % to about 7 %, about 4,3 % to about 7 %, about 4,4 % to about 7 %, about 4,5 % to about 7 %, about 4,6 % to about 7 %, about 4,7 % to about 7 %, about 4,8 % to about 7 %, about 4,9 % to about 7 %, about 5 % to about 7 %, about 5,1 % to about 7 %, about 5,2 % to about 7 %, about 5,3 % to about 7 %, about 5,4 % to about 7 %, about 5,5 % to about 7 %, about 5,6 % to about 7 %, about 5,7 % to about 7 %, about 5,8 % to about 7 %, about 5,9 % to about 7 %, about 6 % to about 7 %, about 6,1 % to about 7 %, about 6,2 % to about 7 %, about

6,3 % to about 7 %, about 6,4 % to about 7 %, about 6,5 % to about 7 %, about 6,6 % to about

7 %, about 6,7 % to about 7 %, about 6,8 % to about 7 %, about 6,9 % to about 7 % of ornithine.

In some embodiments, the composition may comprise the following concentrations of phenylalanine in terms of w / w % : about 0,5 % to about 3 %, about 0,6 % to about 3 %, about 0,7 % to about 3 %, about 0,8 % to about 3 %, about 0,9 % to about 3 %, about 1 % to about 3 %, about 1,1 % to about 3 %, about 1,2 % to about 3 %, about 1,3 % to about 3 %, about 1,4 % to about 3 %, about 1,5 % to about 3 %, about 1,6 % to about 3 %, about 1,7 % to about 3 %, about 1,8 % to about 3 %, about 1,9 % to about 3 %, about 2 % to about 3 %, about 2,1 % to about 3 %, about 2,2 % to about 3 %, about 2,3 % to about 3 %, about 2,4 % to about 3 %, about 2,5 % to about 3 %, about 2,6 % to about 3 %, about 2,7 % to about 3 %, about 2,8 % to about 3 %, about 2,9 % to about 3 % of phenylalanine.

In some embodiments, the composition may comprise the following concentrations of proline in terms of w / w % : about 0 % to about 5 %, about 0,1 % to about 5 %, about 0,2 % to about 5 %, about 0,3 % to about 5 %, about 0,4 % to about 5 %, about 0,5 % to about 5 %, about 0,6 % to about 5 %, about 0,7 % to about 5 %, about 0,8 % to about 5 %, about 0,9 % to about 5 %, about 1 % to about 5 %, about 1,1 % to about 5 %, about 1,2 % to about 5 %, about 1,3 % to about 5 %, about 1,4 % to about 5 %, about 1,5 % to about 5 %, about 1,6 % to about 5 %, about 1,7 % to about 5 %, about 1,8 % to about 5 %, about 1,9 % to about 5 %, about 2 % to about 5 %, about 2,1 % to about 5 %, about 2,2 % to about 5 %, about 2,3 % to about 5 %, about 2,4 % to about 5 %, about 2,5 % to about 5 %, about 2,6 % to about 5 %, about 2,7 % to about 5 %, about 2,8 % to about 5 %, about 2,9 % to about 5 %, about 3 % to about 5 %, about 3,1 % to about 5 %, about 3,2 % to about 5 %, about 3,3 % to about 5 %, about 3,4 % to about 5 %, about 3,5 % to about 5 %, about 3,6 % to about 5 %, about 3,7 % to about 5 %, about 3,8 % to about 5 %, about 3,9 % to about 5 %, about 4 % to about 5 %, about 4,1 % to about 5 %, about 4,1 % to about 5 %, about 4,2 % to about 5 %, about 4,3 % to about 5 %, about 4,4 % to about 5 %, about 4,5 % to about 5 %, about 4,6 % to about 5 %, about 4,7 % to about 5 %, about 4,8 % to about 5 %, about 4,9 % to about 5 % of proline.

In some embodiments, the composition may comprise the following concentrations of serine in terms of w / w % : about 3 % to about 15 %, about 3,1 % to about 15 %, about 3,2 % to about 15 %, about 3,3 % to about 15 %, about 3,4 % to about 15 %, about 3,5 % to about 15 %, about 3.6 % to about 15 %, about 3,7 % to about 15 %, about 3,8 % to about 15 %, about 3,9 % to about 15 %, about 4 % to about 15 %, about 4,1 % to about 15 %, about 4,2 % to about 15 %, about 4,3 % to about 15 %, about 4,4 % to about 15 %, about 4,5 % to about 15 %, about 4,6 % to about 15 %, about 4,7 % to about 15 %, about 4,8 % to about 15 %, about 4,9 % to about 15 %, about 5 % to about 15 %, about 5,1 % to about 15 %, about 5,2 % to about 15 %, about

5.3 % to about 15 %, about 5,4 % to about 15 %, about 5,5 % to about 15 %, about 5,6 % to about 15 %, about 5,7 % to about 15 %, about 5,8 % to about 15 %, about 5,9 % to about 15 %, about 6 % to about 15 %, about 6,1 % to about 15 %, about 6,2 % to about 15 %, about 6,3 % to about 15 %, about 6,4 % to about 15 %, about 6,5 % to about 15 %, about 6,6 % to about 15 %, about 6,7 % to about 15 %, about 6,8 % to about 15 %, about 6,9 % to about 15 %, about 7 % to about 15 %, about 7,1 % to about 15 %, about 7,2 % to about 15 %, about 7,3 % to about 15 %, about 7,4 % to about 15 %, about 7,5 % to about 15 %, about 7,6 % to about 15 %, about

7.7 % to about 15 %, about 7,8 % to about 15 %, about 7,9 % to about 15 %, about 8 % to about 15 %, about 8,1 % to about 15 %, about 8,2 % to about 15 %, about 8,3 % to about 15 %, about

8.4 % to about 15 %, about 8,5 % to about 15 %, about 8,6 % to about 15 %, about 8,7 % to about 15 %, about 8,8 % to about 15 %, about 8,9 % to about 15 %, about 9 % to about 15 %, about 9,1 % to about 15 %, about 9,2 % to about 15 %, about 9,3 % to about 15 %, about 9,4 % to about 15 %, about 9,5 % to about 15 %, about 9,6 % to about 15 %, about 9,7 % to about 15 %, about 9,8 % to about 15 %, about 9,9 % to about 15 %, about 10 % to about 15 %, about 10,1 % to about 15 %, about 10,2 % to about 15 %, about 10,3 % to about 15 %, about 10,4 % to about 15 %, about 10,5 % to about 15 %, about 10,6 % to about 15 %, about 10,7 % to about 15 %, about 10,8 % to about 15 %, about 10,9 % to about 15 %, about 11 % to about 15 %, about 11,1 % to about 15 %, about 11,2 % to about 15 %, about 11,3 % to about 15 %, about

11.4 % to about 15 %, about 11,5 % to about 15 %, about 11,6 % to about 15 %, about 11,7 % to about 15 %, about 11,8 % to about 15 %, about 11,9 % to about 15 %, about 12 % to about 15 %, about 12,1 % to about 15 %, about 12,2 % to about 15 %, about 12,3 % to about 15 %, about 12,4 % to about 15 %, about 12,5 % to about 15 %, about 12,6 % to about 15 %, about

12.7 % to about 15 %, about 12,8 % to about 15 %, about 12,9 % to about 15 %, about 13 % to about 15 %, about 13,1 % to about 15 %, about 13,2 % to about 15 %, about 13,3 % to about 15 %, about 13,4 % to about 15 %, about 13,5 % to about 15 %, about 13,6 % to about 15 %, about 13,7 % to about 15 %, about 13,8 % to about 15 %, about 13,9 % to about 15 %, about 14 % to about 15 %, about 14,1 % to about 15 %, about 14,2 % to about 15 %, about 14,3 % to about 15 %, about 14,4 % to about 15 %, about 14,5 % to about 15 %, about 14,6 % to about 15 %, about 14,7 % to about 15 %, about 14,8 % to about 15 %, about 14,9 % to about 15 % of serine.

In some embodiments, the composition may comprise the following concentrations of taurine in terms of w / w % : about 25 % to about 45 %, about 25,1 % to about 45 %, about 25,2 % to about 45 %, about 25,3 % to about 45 %, about 25,4 % to about 45 %, about 25,5 % to about 45 %, about 25,6 % to about 45 %, about 25,7 % to about 45 %, about 25,8 % to about 45 %, about 25,9 % to about 45 %, about 26 % to about 45 %, about 26,1 % to about 45 %, about 26,2 % to about 45 %, about 26,3 % to about 45 %, about 26,4 % to about 45 %, about 26,5 % to about 45 %, about 26,6 % to about 45 %, about 26,7 % to about 45 %, about 26,8 % to about 45 %, about 26,9 % to about 45 %, about 27 % to about 45 %, about 27,1 % to about 45 %, about 27,2 % to about 45 %, about 27,3 % to about 45 %, about 27,4 % to about 45 %, about 27,5 % to about 45 %, about 27,6 % to about 45 %, about 27,7 % to about 45 %, about 27,8 % to about 45 %, about 27,9 % to about 45 %, about 28 % to about 45 %, about 28,1 % to about 45 %, about 28,2 % to about 45 %, about 28,3 % to about 45 %, about 28,4 % to about 45 %, about 28,5 % to about 45 %, about 28,6 % to about 45 %, about 28,7 % to about 45 %, about 28,8 % to about 45 %, about 28,9 % to about 45 %, about 29 % to about 45 %, about 29, 1 % to about 45 %, about 29,2 % to about 45 %, about 29,3 % to about 45 %, about 29,4 % to about 45 %, about 29,5 % to about 45 %, about 29,6 % to about 45 %, about 29,7 % to about 45 %, about 29,8 % to about 45 %, about 29,9 % to about 45 %, about 30 % to about 45 %, about 30,1 % to about 45 %, about 30,2 % to about 45 %, about 30,3 % to about 45 %, about 30,4 % to about 45 %, about 30,5 % to about 45 %, about 30,6 % to about 45 %, about 30,7 % to about 45 %, about 30,8 % to about 45 %, about 30,9 % to about 45 %, about 31 % to about 45 %, about 31,1 % to about 45 %, about 31,2 % to about 45 %, about 31,3 % to about 45 %, about 31,4 % to about 45 %, about 31,5 % to about 45 %, about 31,6 % to about 45 %, about 31,7 % to about 45 %, about 31,8 % to about 45 %, about 31,9 % to about 45 %, about 32 % to about 45 %, about 32,1 % to about 45 %, about 32,2 % to about 45 %, about 32,3 % to about 45 %, about 32,4 % to about 45 %, about 32,5 % to about 45 %, about 32,6 % to about 45 %, about 32,7 % to about 45 %, about 32,8 % to about 45 %, about 32,9 % to about 45 %, about 33 % to about 45 %, about 33,1 % to about 45 %, about 33,2 % to about 45 %, about 33,3 % to about 45 %, about 33,4 % to about 45 %, about 33,5 % to about 45 %, about 33,6 % to about 45 %, about 33,7 % to about 45 %, about 33,8 % to about 45 %, about 33,9 % to about 45 %, about 34 % to about 45 %, about 34,1 % to about 45 %, about 34,2 % to about 45 %, about 34,3 % to about 45 %, about 34,4 % to about 45 %, about 34,5 % to about 45 %, about 34,6 % to about 45 %, about 34,7 % to about 45 %, about 34,8 % to about 45 %, about 34,9 % to about 45 %, about 35 % to about 45 %, about 35,1 % to about 45 %, about 35,2 % to about 45 %, about 35,3 % to about 45 %, about 35,4 % to about 45 %, about 35,5 % to about 45 %, about 35,6 % to about 45 %, about 35,7 % to about 45 %, about 35,8 % to about 45 %, about 35,9 % to about 45 %, about 36 % to about 45 %, about 36,1 % to about 45 %, about 36,2 % to about 45 %, about 36,3 % to about 45 %, about 36,4 % to about 45 %, about 36,5 % to about 45 %, about 36,6 % to about 45 %, about 36,7 % to about 45 %, about 36,8 % to about 45 %, about 36,9 % to about 45 %, about 37 % to about 45 %, about 37,1 % to about 45 %, about 37,2 % to about 45 %, about 37,3 % to about 45 %, about 37,4 % to about 45 %, about 37,5 % to about 45 %, about 37,6 % to about 45 %, about 37,7 % to about 45 %, about 37,8 % to about 45 %, about 37,9 % to about 45 %, about 38 % to about 45 %, about 38,1 % to about 45 %, about 38,2 % to about 45 %, about 38,3 % to about 45 %, about 38,4 % to about 45 %, about 38,5 % to about 45 %, about 38,6 % to about 45 %, about 38,7 % to about 45 %, about 38,8 % to about 45 %, about 38,9 % to about 45 %, about 39 % to about 45 %, about 39,1 % to about 45 %, about 39,2 % to about 45 %, about 39,3 % to about 45 %, about 39,4 % to about 45 %, about 39,5 % to about 45 %, about 39,6 % to about 45 %, about 39,7 % to about 45 %, about 39,8 % to about 45 %, about 39,9 % to about 45 %, about 40 % to about 45 %, about 40,1 % to about 45 %, about 40,2 % to about 45 %, about 40,3 % to about 45 %, about 40,4 % to about 45 %, about 40,5 % to about 45 %, about 40,6 % to about 45 %, about 40,7 % to about 45 %, about 40,8 % to about 45 %, about 40,9 % to about 45 %, about 41 % to about 45 %, about 41,1 % to about 45 %, about 41,2 % to about 45 %, about 41,3 % to about 45 %, about 41,4 % to about 45 %, about 41,5 % to about 45 %, about 41,6 % to about 45 %, about 41,7 % to about 45 %, about 41,8 % to about 45 %, about 41,9 % to about 45 %, about 42 % to about 45 %, about 42,1 % to about 45 %, about 42,2 % to about 45 %, about 42,3 % to about 45 %, about 42,4 % to about 45 %, about 42,5 % to about 45 %, about 42,6 % to about 45 %, about 42,7 % to about 45 %, about 42,8 % to about 45 %, about 42,9 % to about 45 %, about 43 % to about 45 %, about 43,1 % to about 45 %, about 43,2 % to about 45 %, about 43,3 % to about 45 %, about 43,4 % to about 45 %, about 43,5 % to about 45 %, about 43,6 % to about 45 %, about 43,7 % to about 45 %, about 43,8 % to about 45 %, about 43,9 % to about 45 %, about 44 % to about 45 %, about 44, 1 % to about 45 %, about 44,2 % to about 45 %, about 44,3 % to about 45 %, about 44,4 % to about 45 %, about 44,5 % to about 45 %, about 44,6 % to about 45 %, about 44,7 % to about 45 %, about 44,8 % to about 45 %, about 44,9 % to about 45 % of taurine. In some embodiments, the composition may comprise the following concentrations of threonine in terms of w / w % : about 0,5 % to about 4 %, about 0,6 % to about 4 %, about 0,7 % to about 4 %, about 0,8 % to about 4 %, about 0,9 % to about 4 %, about 1 % to about 4 %, about 1,1 % to about 4 %, about 1,2 % to about 4 %, about 1,3 % to about 4 %, about 1,4 % to about 4 %, about 1,5 % to about 4 %, about 1,6 % to about 4 %, about 1,7 % to about 4 %, about 1,8 % to about 4 %, about 1,9 % to about 4 %, about 2 % to about 4 %, about 2,1 % to about 4 %, about 2,2 % to about 4 %, about 2,3 % to about 4 %, about 2,4 % to about 4 %, about 2,5 % to about 4 %, about 2,6 % to about 4 %, about 2,7 % to about 4 %, about 2,8 % to about 4 %, about 2,9 % to about 4 %, about 3 % to about 4 %, about 3,1 % to about 4 %, about 3,2 % to about 4 %, about 3,3 % to about 4 %, about 3,4 % to about 4 %, about 3,5 % to about 4 %, about 3,6 % to about 4 %, about 3,7 % to about 4 %, about 3,8 % to about 4 %, about 3,9 % to about 4 of threonine.

In some embodiments, the composition may comprise the following concentrations of tryptophane in terms of w / w % : about 0 % to about 2 %, about 0,1 % to about 2 %, about 0,2 % to about 2 %, about 0,3 % to about 2 %, about 0,4 % to about 2 %, about 0,5 % to about 2 %, about 0,6 % to about 2 %, about 0,7 % to about 2 %, about 0,8 % to about 2 %, about 0,9 % to about 2 %, about 1 % to about 2 %, about 1,1 % to about 2 %, about 1,2 % to about 2 %, about 1,3 % to about 2 %, about 1,4 % to about 2 %, about 1,5 % to about 2 %, about 1,6 % to about 2 %, about 1,7 % to about 2 %, about 1,8 % to about 2 %, about 1,9 % to about 2 % of tryptophane.

In some embodiments, the composition may comprise the following concentrations of tyrosine in terms of w / w % : about 0 % to about 2 %, about 0,1 % to about 2 %, about 0,2 % to about 2 %, about 0,3 % to about 2 %, about 0,4 % to about 2 %, about 0,5 % to about 2 %, about 0,6 % to about 2 %, about 0,7 % to about 2 %, about 0,8 % to about 2 %, about 0,9 % to about 2 %, about 1 % to about 2 %, about 1,1 % to about 2 %, about 1,2 % to about 2 %, about 1,3 % to about 2 %, about 1,4 % to about 2 %, about 1,5 % to about 2 %, about 1,6 % to about 2 %, about 1,7 % to about 2 %, about 1,8 % to about 2 %, about 1,9 % to about 2 % of tyrosine.

In some embodiments, the composition may comprise the following concentrations of valine in terms of w / w % : about 0,5 % to about 3 %, about 0,6 % to about 3 %, about 0,7 % to about 3

%, about 0,8 % to about 3 %, about 0,9 % to about 3 %, about 1 % to about 3 %, about 1,1 % to about 3 %, about 1,2 % to about 3 %, about 1,3 % to about 3 %, about 1,4 % to about 3 %, about 1,5 % to about 3 %, about 1,6 % to about 3 %, about 1,7 % to about 3 %, about 1,8 % to about 3 %, about 1,9 % to about 3 %, about 2 % to about 3 %, about 2,1 % to about 3 %, about 2,2 % to about 3 %, about 2,3 % to about 3 %, about 2,4 % to about 3 %, about 2,5 % to about 3 %, about 2,6 % to about 3 %, about 2,7 % to about 3 %, about 2,8 % to about 3 %, about 2,9 % to about 3 % of valine.

In some embodiments, the composition may comprise or consist of the following concentrations of amino acids in terms of w / w % : about 3 to 10,5 % of alanine, about 0 to 2 % of arginine, about 0 to 3 % of asparagine, about 0,5 to 5,5 % of aspartate, about 0 to 2 % of P-alanine, about 0 to 5 % of cysteine, about 0 to 2 % of citrulline, about 1 to 5 % of glutamate, about 15 to 35 % of glutamine, about 3,5 to 9 % of glycine, about 1 to 4 % of histidine, about 0,5 to 2 % of isoleucine, about 0,5 to 4 % of leucine, about 0,5 to 4,5 % of lysine, about 0,1 to 3 % of methionine, about 0 to 7 % of ornithine, about 0,5 to 3 % of phenylalanine, about 0 to 5 % of proline, about 3 to 15 % of serine, about 25 to 45 % of taurine, about 0,5 to 4 % of threonine, about 0 to 2 % of tryptophan, about 0 to 2 % of tyrosine and about 0,5 to 3 % of valine.

In exemplary embodiments, the composition may comprise, consist essentially, or consist of 5,20 % of alanine, 0,9 % of arginine, 1,6 % of asparagine, 2,8 % of aspartate, 0,55 % of P- alanine, 0,9 % of citrulline, 2,4 % of glutamate, 23,65 % of glutamine, 4,55 % of glycine, 2,15 % of histidine, 1 % of isoleucine, 1,9 % of leucine, 2,3 % of lysine, 0,4 % of methionine, 3,55 % of ornithine, 0,8 % of phenylalanine, 7,65 % of serine, 33,45 % of taurine, 2 % of threonine, 1,15 % of tyrosine and 1,1 % of valine.

In another aspect, combinations and compositions of the invention may further comprise one or more additional nutrients. The term “nutrient”, as used herein, refers to prebiotics, vitamins, carbohydrates, fiber, fatty acids, sulfates, minerals, antioxidants, and other food ingredients used in subject's metabolism which are taken in from its environment. Suitable vitamins may include, but are not limited to: vitamin Bl, vitamin B2, vitamin B3, vitamin B5, vitamin B6, vitamin B9, vitamin B 12, lipoic acid, vitamin A, biotin, vitamin K, vitamin C, vitamin D, and vitamin E. Suitable minerals may include, but are not limited to compounds containing: iron, copper, magnesium, manganese, molybdenum, nickel, and zinc. Suitable enzyme cofactors may include, but are not limited to: adenosine triphosphate (ATP), S - adenosyl methionine (SAM), coenzyme B, coenzyme M, coenzyme Q, glutathione, heme, methanofuran, and nucleotide sugars. Suitable lipids may include, but are not limited to, fatty acids, glycerolipids, glycerophospholipids, sphingolipids, sterol lipids, prenol lipids, saccharolipids and polyketides. Non - limiting examples of fatty acids include myristoleic acid, palm itoleic acid, sapienic acid, oleic acid, elaidic acid, vaccenic acid, linoleic acid, linoelaidic acid, arachidonic acid, eicosapentaenoic acid, erucic acid, docosahexaenoic acid, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid, lignoceric acid, cerotic acid, hexadecatrienoicacid, alpha - linolenic acid, stearidonic acid, eicosatetraenoic acid, eicosapentaenoic acid, heneicosapentaenoic acid, docosapentaenoic acid, clupanodonic acid, docasehaenoic acid, tetracosapentaenoic acid, and tetracosahexaenoic acid. Additional non - limiting examples of nutrients may include Thiamin, Riboflavin, Niacin, Folate, Pantothenic acid, Calcium, Phosphorus, Magnesium, Manganese, Iron, Zinc, Copper, Selenium, Sodium, Potassium, betacarotene, retinol, alphatocopherol, betatocopherol, gammatocopherol, deltatocopherol, alphatoctrienol, betatoctrienol, gammatocotrienol, del tatocotri enol, gamma- Aminobutyric acid (GABA), creatin, apo - 8 - carotenal, trans - lycopene, cis - lycopene, trans - beta - carotene, and cis - beta - carotene caffeine. In some embodiments, combinations and compositions of the invention further comprise one nutrient. In other embodiments, combinations and compositions of the invention further comprise at least one nutrient. For example, a combination and a composition of the invention may comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more nutrients. In still other embodiments, combinations and compositions of the invention further comprise two or more nutrients.

In preferred embodiments, combinations and compositions of the invention further comprise at least one nutrient selected from the group consisting of omega - 3 fatty acid, biotin, gamma- Aminobutyric acid (GABA) and creatin. In other preferred embodiments, combinations and compositions of the invention further comprise two nutrients selected from the group consisting omega - 3 fatty acid, biotin, gamma-Aminobutyric acid (GABA) and creatin. The overall contribution of the one or more nutrients to the total weight of the combination and the composition is substantially less than the contribution of the plurality of amino acids. Generally, the one or more nutrients comprise no more than about 50 % by weight, preferably no more than about 10 % by weight, more preferably no more than about 5 % by weight of the combination or composition.

In another aspect, combinations and compositions of the invention may further comprise one or more additional companion product. The term “companion product”, as used herein, refers to a product which is supposed to be taken with the first product. The composition may comprise the following concentrations of amino acids in terms of w / w % and may be repartited in several companion product: about 3 to 10,5 % of alanine, about 0 to 2 % of arginine, about 0 to 3 % of asparagine, about 0,5 to 5,5 % of aspartate, about 0 to 2 % of P-alanine, about 0 to 5 % of cysteine, about 0 to 2 % of citrulline, about 1 to 5 % of glutamate, about 15 to 35 % of glutamine, about 3,5 to 9 % of glycine, about 1 to 4 % of histidine, about 0,5 to 2 % of isoleucine, about 0,5 to 4 % of leucine, about 0,5 to 4,5 % of lysine, about 0,1 to 3 % of methionine, about 0 to 7 % of ornithine, about 0,5 to 3 % of phenylalanine, about 0 to 5 % of proline, about 3 to 15 % of serine, about 25 to 45 % of taurine, about 0,5 to 4 % of threonine, about 0 to 2 % of tryptophan, about 0 to 2 % of tyrosine and about 0,5 to 3 % of valine.

In each of the above embodiments, amino acids and nutrients (when present) may be formulated for animal or human use. In some embodiments, each amino acid and nutrient (when present) is formulated separately. In other embodiments, two or more amino acids and nutrients (when present) are formulated together. In still other embodiments, all the amino acids and nutrients comprising a combination of the invention are formulated together. The one or more formulations may then be processed into one or more dosage forms that can be administered simultaneously (together), separately, sequentially, or over a period of time (for example, over 1 minute, 10 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, 9 hours, 12 hours, 18 hours, 24 hours, or more). In preferred embodiments all component of the recipe are taken the same day and preferably before exercise and until Ih after exercise for higher efficiency. For those who perform no physical exercise it is completely independent of the time. Administration can be performed using standard effective techniques, including oral, parenteral (e.g. intravenous, intraperitoneal, subcutaneous, intramuscular), buccal, sublingual, or suppository administration. The term orally, as used herein, refers to any form of administration by mouth, including addition of a composition to human or animal food product. Formulation of pharmaceutical compositions is discussed in, for example, Hoover, John E., Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pa. ( 1975 ), and Liberman, H. A. and Lachman, L., Eds., Pharmaceutical Dosage Forms, Marcel Decker, New York, N.Y. ( 1980 ).

Methods of preparing compositions for animal or human use are well known in the art. For instance, a composition may be generally formulated as a liquid composition, a solid composition or a semi - solid composition. Liquid compositions include, but are not limited to, aqueous suspensions, solutions, emulsions, elixirs, or syrups. Liquid composition will typically include a solvent carrier selected from a polar solvent, a non - polar solvent, or a combination of both. The choice of solvent will be influenced by the properties of the components of the composition. For example, if the components are water - soluble, a polar solvent may be used. Alternatively, if the components of the composition are lipid - soluble, a non - polar solvent may be used. Suitable polar and non - polar solvents are known in the art. Semi - solid compositions include douches, suppositories, creams, and topicals. Dry compositions include, but are not limited to, reconstitutable powders, chewable tablets, quick dissolve tablets, effervescent tablets, multi - layer tablets, bi - layer tablets, capsules, soft capsules, hard capsules, caplets, lozenges, chewable lozenges, beads, powders, granules, particles, microparticles, and dispersible granules. Formulations may include a combination of the invention along with an excipient. Non - limiting examples of excipients include binders, diluents (fillers ), disintegrants, effervescent disintegration agents, preservatives ( antioxidants ), flavor - modifying agents, lubricants and glidants, dispersants, coloring agents, pH modifiers, chelating agents, antimicrobial agents, release - controlling polymers, and combinations of any of these agents.

Non - limiting examples of binders suitable for the formulations of various embodiments include starches, pregelatinized starches, gelatin, polyvinylpyrolidone, cellulose, methylcellulose, sodium carboxymethylcellulose, ethylcellulose, polyacrylamides, polyvinyloxoazolidone, polyvinylalcohols, C12 - Ci8 fatty acid alcohols, polyethylene glycol, polyols, saccharides, oligosaccharides, polypeptides, oligopeptides, and combinations thereof. The polypeptide be any arrangement of amino acids ranging from about 100 to about 300,000 Daltons. In one embodiment, the binder may be introduced into the mixture to be granulated in a solid form including but not limited to a crystal, a particle, a powder, or any other finely divided solid form known in the art. In another embodiment, the binder may be dissolved or suspended in a solvent and sprayed onto the mixture in a granulation device as a binder fluid during granulation.

Non - limiting examples of diluents (also referred to as " fillers " or " thinners ”) include carbohydrates, inorganic compounds, and biocompatible polymers, such as polyvinylpirrolydone ( PVP ). Other non - limiting examples of diluents include dibasic calcium sulfate, tribasic calcium sulfate, starch, calcium carbonate, magnesium carbonate, microcrystalline cellulose, dibasic calcium phosphate, tribasic calcium phosphate, magnesium carbonate, magnesium oxide, calcium silicate, talc, modified starches, saccharides such as sucrose, dextrose, lactose, microcrystalline cellulose, fructose, xylitol, and sorbitol, polyhydric alcohols; starches; pre - manufactured direct compression diluents; and mixtures of any of the foregoing.

Disintegrants may be effervescent or non - effervescent. Non - limiting examples of non - effervescent disintegrants include starches such as com starch, potato starch, pregelatinized and modified starches thereof, sweeteners, clays, such as bentonite, micro - crystalline cellulose, alginates, sodium starch glycolate, gums such as agar, guar, locust bean, karaya, pecitin, and tragacanth. Suitable effervescent disintegrants include but are not limited to sodium bicarbonate in combination with citric acid, and sodium bicarbonate in combination with tartaric acid.

Non - limiting examples of preservatives include, but are not limited to, ascorbic acid and its salts, ascorbyl palmitate, ascorbyl stearate, anoxomer, N - acetylcysteine, benzyl isothiocyanate, m - aminobenzoic acid, o - aminobenzoic acid, p - aminobenzoic acid ( PABA ), butylated hydroxyanisole ( BHA ), butylated hydroxytoluene ( BHT ), caffeic acid, canthaxantin, alpha - carotene, beta - carotene, beta-caraotene, beta-apo - carotenoic acid, carnosol, carvacrol, catechins, cetyl gallate, chlorogenic acid, citric acid and its salts, clove extract, coffee bean extract, p - coumaric acid, 3,4 - dihydroxybenzoic acid, N, N ' - diphenyl - p - phenylenediamine ( DPPD ), dilauryl thiodipropionate, distearyl thiodipropionate, 2,6 - di - tert - butylphenol, dodecyl gallate, edetic acid, ellagic acid, erythorbic acid, sodium erythorbate, esculetin, esculin, 6 - ethoxy - 1,2 - dihydro - 2,2,4 - trimethylquinoline, ethyl gallate, ethyl maltol, ethylenediaminetetraacetic acid ( EDTA ), eucalyptus extract, eugenol, ferulic acid, flavonoids ( e.g., catechin, epicatechin, epicatechin gallate, epigallocatechin ( EGC ), epigallocatechin gallate ( EGCG ), polyphenol epigallocatechin - 3 - gallate ), flavones ( e.g., apigenin, chrysin, luteolin ), flavonols ( e.g., datiscetin, myricetin, daemfero ), flavanones, fraxetin, fumaric acid, gallic acid, gentian extract, gluconic acid, glycine, gum guaiacum, hesperetin, alpha - hydroxybenzyl phosphinic acid, hydroxycinammic acid, hydroxyglutaric acid, hydroquinone, N - hydroxysuccinic acid, hydroxytryrosol, hydroxyurea, rice bran extract, lactic acid and its salts, lecithin, lecithin citrate; R - alpha - lipoic acid, lutein, lycopene, malic acid, maltol, 5 - methoxy tryptamine, methyl gallate, monoglyceride citrate; monoisopropyl citrate; morin, beta - naphthoflavone, nordihydroguaiaretic acid ( NDGA ), octyl gallate, oxalic acid, palm ityl citrate, phenothiazine, phosphatidylcholine, phosphoric acid, phosphates, phyticacid, phytylubichromel, pimento extract, propyl gallate, polyphosphates, quercetin, trans - resveratrol, rosemary extract, rosmarinic acid, sage extract, sesamol, silymarin, sinapic acid, succinic acid, stearyl citrate, syringic acid, tartaric acid, thymol, tocopherols ( i.e., alpha-, beta- , gamma and delta - tocopherol ), tocotrienols ( i.e., alpha-, beta-, gamma- and delta - tocotrienols ), tyrosol, vanilic acid, 2,6 di - tert - butyl - 4 - hydroxymethylphenol ( i.e., lonox 100 ), 2,4 ( tris - 3 ', 5 - bi - tert - butyl - 4 - hydroxybenzyl ) -mesitylene ( i.e., lonox 330 ), 2,4,5

- trihydroxybutyrophenone, ubiquinone, tertiary butyl hydroquinone ( TBHQ ), thiodipropionic acid, trihydroxy butyrophenone, tryptamine, tyramine, uric acid, vitamin K and derivates, vitamin Q10, wheat germ oil, zeaxanthin, or combinations thereof. In an exemplary embodiment, the preservative is an antioxidant, such as a - tocopherol or ascorbate.

Suitable flavour - modifying agents include flavourants, taste - masking agents, sweeteners, and the like. Flavourants include, but are not limited to, synthetic flavour oils and flavouring aromatics and / or natural oils, extracts from plants, leaves, flowers, fruits, and combinations thereof. Other non - limiting examples of flavours include cinnamon oils, oil of wintergreen, peppermint oils, clover oil, hay oil, anise oil, eucalyptus, vanilla, cocoa, citrus oils such as lemon oil, orange oil, grape and grapefruit oil, fruit essences including apple, peach, pear, strawberry, raspberry, cherry, plum, pineapple, and apricot.

Taste - masking agents include but are not limited to cellulose hydroxypropyl ethers ( HPC ) such as Klucel®, Nisswo HPC and PrimaFlo HP22; low - substituted hydroxypropyl ethers ( L

- HPC ); cellulose hydroxypropyl methylethers ( HPMC ) such as Seppifilm - LC, Pharmacoat®, Metolose SR, Opadry YS, PrimaFlo, MP3295A, Benecel MP824, and Benecel MP843; methylcellulose polymers such as Methocel® and Metolose®; Ethylcelluloses ( EC ) and mixtures thereof such as E461, Ethocel®, Aquaion® - EC, Sure lease; Polyvinyl alcohol ( PVA ) such as Opadry AMB; hydroxyethylcelluloses such as Natrosol®; carboxymethyl celluloses and salts of carboxymethylcelluloses ( CMC ) such as Aualon® - CMC; polyvinyl alcohol and polyethylene glycol co - polymers such as Kollicoat IR®; monoglycerides ( Myverol ), triglycerides ( KLX ), polyethylene glycols, modified food starch, acrylic polymers and mixtures of acrylic polymers with cellulose ethers such as Eudragit® EPO, Eudragit® RD 100, and Eudragit® El 00; cellulose acetate phthalate; sepifilms such as mixtures of HPMC and stearic acid, cyclodextrins, and mixtures of these materials. In other embodiments, additional taste - masking agents contemplated are those described in U.S. Pat. Nos. 4,851,226,5,075,114, and 5,876,759, each of which is hereby incorporated by reference in its entirety. Non - limiting examples of sweeteners include glucose (corn syrup), dextrose, invert sugar, fructose, and mixtures thereof ( when not used as a carrier ); saccharin and its various salts such as the sodium salt; dipeptide sweeteners such as aspartame; dihydrochalcone compounds, glycyrrhizin; Stevia rebaudiana ( Stevioside ); chloro derivatives of sucrose such as sucralose; sugar alcohols such as sorbitol, mannitol, xylitol, hydrogenated starch hydrolysates and the synthetic sweetener 3,6 - dihydro - 6 - methyl - 1,2,3 - oxathiazin 4 - one - 2,2 - dioxide, particularly the potassium salt ( acesulfame - K ), and sodium and calcium salts thereof.

Lubricants may be utilized to lubricate ingredients that form a composition of the invention. As a glidant, the lubricant facilitates removal of solid dosage forms during the manufacturing process. Non - limiting examples of lubricants and glidants include magnesium stearate, calcium stearate, zinc stearate, hydrogenated vegetable oils, sterotex, polyoxyethylene monostearate, talc, polyethylene glycol, sodium benzoate, sodium lauryl sulfate, magnesium lauryl sulfate, and light mineral oil. The composition will generally comprise from about 0.01 % to about 10 % by weight of a lubricant. In some embodiments, the composition will comprise from about 0.1 % to about 5 % by weight of a lubricant. In a further embodiment, the composition will comprise from about 0.5 % to about 2 % by weight of a lubricant.

Dispersants may include but are not limited to starch, alginic acid, polyvinylpyrrolidones, guar gum, kaolin, bentonite, purified wood cellulose, sodium starch glycolate, isoamorphous silicate, and microcrystalline cellulose as high hydrophilic - lipophilic balance ( HLB ) emulsifier surfactants.

Depending upon the embodiment, it may be desirable to include a colouring agent. Suitable colour additives include but are not limited to food, drug and cosmetic colours ( FD & C ), drug and cosmetic colours ( D & C ), or external drug and cosmetic colours ( Ext. D & C ). These colours or dyes, along with their corresponding lakes, and certain natural and derived colorants may be suitable for use in various embodiments.

Non - limiting examples of pH modifiers include citric acid, acetic acid, tartaric acid, malic acid, fumaric acid, lactic acid, phosphoric acid, sorbic acid, benzoic acid, sodium carbonate and sodium bicarbonate. A chelating agent may be included as an excipient to immobilize oxidative groups, including but not limited to metal ions, in order to inhibit the oxidative degradation of the morphinan by these oxidative groups. Non - limiting examples of chelating agents include lysine, methionine, glycine, gluconate, polysaccharides, glutamate, aspartate, and disodium ethylenediaminetetraacetate ( Na’EDTA ).

An antimicrobial agent may be included as an excipient to minimize the degradation of the compound according to this disclosure by microbial agents, including but not limited to bacteria and fungi. Non - limiting examples of antimicrobials include parabens, chlorobutanol, phenol, calcium propionate, sodium nitrate, sodium nitrite, Na’EDTA, and sulfites including but not limited to sulfurdioxide, sodium bisulfite, and potassium hydrogen sulfite.

Release - controlling polymers may be included in the various embodiments of the solid dosage compositions incorporating compounds according to this disclosure. In some embodiment, the release - controlling polymers may be used as a tablet coating. In other embodiments, including but not limited to bilayer tablets, a release - controlling polymer may be mixed with the granules and other excipients prior to the formation of a tablet by a known process including but not limited to compression in a tablet mould. Suitable release controlling polymers include but are not limited to hydrophilic polymers and hydrophobic polymers. In preferred embodiments, controlled and/or sustained release tablet may include one or more amino acids preferably P- alanine as the sole amino acid or P-alanine and one or more amino acids.

As used herein, "sustained release" can mean any one of a number of extended-release dosage forms. The various sustained release technologies cover a very broad spectrum of drug dosage forms. Sustained release technologies include typically chemical systems that include, but are not limited to, chemical erosion of polymer matrices (e.g., heterogeneous or homogeneous erosion) or biological erosion of a polymer matrix (e.g., heterogeneous, or homogeneous). Hydrogels may also be employed as described in "Controlled Release Systems: Fabrication Technology", Vol. II, Chapter 3; pages 41-60; "Gels For Drug Delivery", Edited By Hsieh, D. There are a number of sustained release drug formulations that have been developed. These include, but are not limited to, microencapsulated powders; osmotic pressure-controlled gastrointestinal delivery systems; hydrodynamic pressure-controlled gastrointestinal delivery systems; membrane permeation-controlled gastrointestinal delivery systems, which include microporous membrane permeation-controlled gastrointestinal delivery devices; gel diffusion controlled gastrointestinal delivery systems; and ion-exchange-controlled gastrointestinal delivery systems, which include cationic and anionic drugs. In one embodiment, the sustained release system can be an oil-microencapsulated sustained release powder dosage form that can be mixed with liquid and consumed as a drink mix beverage. Furthermore, many of the conventional pharmaceutical carriers, binders, excipients and additives, when used in sufficient quantities, can act as controlled-release polymers and produce a sustained release effect. These include, but are not limited to, gelatin, natural sugars such as raw sugar or lactose, lecithin, mucilage, plant gums, pectins or pectin derivatives, algal polysaccharides, glucomannan, agar and lignin, guar gum, locust bean gum, acacia gum, xanthan gum, carrageenan gum, karaya gum, tragacanth gum, ghatti gum, starches (e.g., corn starch or amylose), dextran, polyvinyl pyrrolidone, polyvinyl acetate, gum arabic, alginic acid, tylose, talcum, lycopodium, silica gel (e.g., colloidal), cellulose and cellulose derivatives (e.g., cellulose ethers, cellulose ethers in which the cellulose hydroxy groups are partially ethenfied with lower saturated aliphatic alcohols and/or lower saturated, aliphatic oxyalcohols; e.g., methyloxypropyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl methyl cellulose phthalate, crosslinked sodium carboxymethylcellulose, cross-linked hydroxypropylcellulose, high-molecular weight hydroxymethylpropycellulose, carboxymethyl-cellulose, low-molecular weight hydroxypropylmethylcellulose medium -viscosity hydroxyptopylmethylcellulose hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, sodium caiboxymethylcelulose, alkylcelluloses, ethyl cellulose, cellulose acetate, cellulose propionate (low, medium or high molecular weight), cellulose acetatepropionate, cellulose acetate butyrate, cellulose triacetate, methyl cellulose, hydroxypropyl cellulose, orhydroxypropylmefhyl cellulose), fatty acids as well as magnesium, calcium or aluminum salts of fatty acids with 12 to 22 carbon atoms, in particular saturated fatty acids (e.g., stearates such as magnesium stearate), polycarboxylic acids, emulsifiers, oils and fats, in particular vegetable (e.g., peanut oil, castor oil, olive oil, sesame oil, cottonseed oil, corn oil, wheat germ oil, sunflower seed oil, cod liver oil, in each case also optionally hydrated); glycerol esters and polyglycerol esters of saturated fatty acids (e.g., C12H24O2 to CisHaeCh) and their mixtures, it being possible for the glycerol hydroxy groups to be totally or also only partly esterified (e.g., mono-, di-and triglycerides); high melting point hydrogenated vegetable oils suitable for microencapsulation; pharmaceutically acceptable mono-or multivalent alcohols and polyglycols such as polyethylene glycol and derivatives thereof, esters of aliphatic saturated or unsaturated fatty acids (e.g., 2 to 22 carbon atoms, e.g., 10-18 carbon atoms) with monovalent aliphatic alcohols (e.g., 1 to 20 carbon atoms) or multivalent alcohols such as glycols, glycerol, diethylene glycol, pentacrythritol, sorbitol, mannitol and the like, which may optionally also be etherified, esters of citric acid with primary alcohols, acetic acid, urea, benzyl benzoate, dioxolanes, glyceroformals, tetrahydrofurfuryl alcohol, polyglycol ethers with C1-C12 alcohols, dimethylacetamide, lactamides, lactates, ethylcarbonates, silicones (e.g., medium -viscous polydimethyl siloxanes), calcium carbonate, sodium carbonate, calcium phosphate, sodium phosphate, magnesium carbonate and the like.

In addition, coating agents may be used to create or enhance the sustained release features of the P-alanine composition of the invention. For example, plasticizers that are useful as coating agents include, but are not limited to, citric and tartaric acid esters (acetyl -tri ethyl citrate, acetyl tributyl-, tributyl-, triethyl- citrate); glycerol and glycerol esters (glyceroldiacetate, -triacetate, acerylated monoglycerides, castor oil); phthalic acid esters (dibutyl-, diarayl-, diethyl-, dimethyl-, dipropyl-phthalate),di- (2- methoxy-or2-ethoxyethyl)-phthalate, ethylphthalyl glycolate, butylphthalylethyl glycolate and butylglycolate; alcohols (propylene glycol, polyethylene glycol of various chain lengths); adipates (diethyladipate, di (2-methoxy-or 2- ethoxyethyl)-adipate; benzophenone; diethyl-and diburylsebacate; dibulyl succinate; dibutyltartrate; diethylene glycol dipropionate; ethyleneglycol di acetate, -dibuty rate, - dipropionate; tributyl phosphate, tributyrin; polyethylene glycol sorbitan monooleate; polysorbates such as Polysorbar 50; and sorbitan monooleate.

Methods of making sustained release compositions are known in the art. For example, coating agents such as ethylcellulose and hydroxypropyl methylcellulose can be mixed together and sprayed onto P-alanine or a biological source thereof in a fluid bed granulator. Another method of making a sustained release pharmaceutical composition employs mixtures of a high temperature melted vegetable oil (e.g., having an iodine value maximum of about 5 and a melting point of about 145° F) with a cellulose ether such as ethylcellulose. This combination can be processed in a vertical or horizontal high intensity mixer or a blender that is jacketed so as to allow a hot water bath to circulate around the mixer to elevate the temperature of the oil to the melting point. Powdered P-alanine or a biological source thereof is then mixed with the molten oil until complete coverage is achieved (about 5-10 minutes), cooled, and the ethylcellulose sprayed onto the particles. The finished product is a microencapsulated, free- flowing sustained-release powder with an extended-release profile. See, also, U.S. Patent Nos. 6,835,397; 6,013,286; and 5,190,775 for methods describing controlled release of encapsulated bioactive substances. Suitable hydrophilic release - controlling polymers include, but are not limited to, cellulose acetate, cellulose diacetate, cellulose triacetate, cellulose ethers, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, microcrystalline cellulose, nitrocellulose, cross linked starch, agar, casein, chitin, collagen, gelatin, maltose, mannitol, maltodextrin, pectin, pullulan, sorbitol, xylitol, polysaccharides, ammonia alginate, sodium alginate, calcium alginate, potassium alginate, propylene glycol alginate, alginate sodium carmellose, calcium carmellose, carrageenan, fucoidan, furcellaran, arabicgum, carrageensgum, ghaftigum, guargum, karayagum, locust beangum, okragum, tragacanthgum, scleroglucangum, xanthangum, hypnea, laminaran, acrylic polymers, acrylate polymers, carboxyvinyl polymers, copolymers of maleic anhydride and styrene, copolymers of maleic anhydride and ethylene, copolymers of maleic anhydride propylene or copolymers of maleic anhydride isobutylene ), crosslinked polyvinyl alcohol and poly N - vinyl - 2 - pyrrolidone, diesters of polyglucan, polyacrylamides, polyacrylic acid, polyamides, polyethylene glycols, polyethylene oxides, poly ( hydroxyalkyl methacrylate ), polyvinyl acetate, polyvinyl alcohol, polyvinyl chloride, polystyrenes, polyvinylpyrrolidone, anionic and cationic hydrogels, and combinations thereof.

The amino acid compositions as disclosed herein can also include compositions that can be created as a powder that can be added to food items, as a baked good ( e.g., as cookies and brownies ), and as a concentrate. The concentrate can be added to water or another ingestible liquid to create a nutritional beverage. The nutritional supplement is typically contained within a one - serving or multiple serving container such as a package, box, carton, wrapper, bottle or can. Where the nutritional supplement is prepared in the form of a concentrate that can be added to and mixed with a beverage, a bottle or can be used for packaging the concentrate. The nutritional supplement can also include water.

As will be appreciated by one of skill in the art, the dose of the combination of the invention and the amino acid composition of the invention can and will vary depending on the body weight, sex, age and / or medical condition of the subject, the intensity of the physical exercise by the subject, the method of administration. Non limiting examples of species may include a human, a companion animal, a lab animal, a zoo animal or an agricultural animal. Routine experimentation may readily establish the required dosage. Typical amino acid doses for oral administration may be about 3 g per dose. In some embodiments, an amino acid dose of about 100 mg, 300 mg, 500 mg, 1g, 2g, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40 , 45 or 50 g of the amino acid composition may be administered. In other embodiments, an amino acid dose of about 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1g, 2g, 3, 4, 5, 10,11,12,13,14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50g of the amino acid composition may be administered.

In an exemplary embodiment, adolescent or adults the amino acid dose may be about 3g. In another exemplary embodiment, for children or babies the amino acid dose may be about 500 mg.

Administering multiple doses of the amino acid composition per day may also be used as needed to provide the desired stimulation of muscle protein synthesis. For instance, one, two, three, four, or more doses of the amino acid composition may be administered per day. In preferred embodiment, one dose of the amino acid composition may be administered per day. In another preferred embodiment, two doses of the amino acid composition may be administered per day. In yet another preferred embodiment, three doses of the amino acid composition may be administered per day.

The timing and duration of administration of the combination of the invention and the composition of the invention can and will vary. For instance, when the combination or the composition is administered to stimulate muscle protein synthesis with or without exercise, the composition may be administered without an exercise routine, before starting an exercise routine, during the exercise routine or after an exercise routine. Alternatively, when the combination or the composition is administered to improve muscle protein synthesis in a subject prone to muscle issues such as an older human subject, the combination or the composition may be administered on a regular basis.

In an exemplary embodiment, three doses of 3 g per dose of the amino acid composition may be administered per day. In another exemplary embodiment, two doses of 3 g per dose of the amino acid composition may be administered per day. In yet another exemplary embodiment, a single dose of 3 g per dose of the amino acid composition may be administered per day. The combination of the invention or the composition of the invention may be administered as intravenous, intramuscular, subcutaneous injection or parenteral routes. In some embodiments, the combination or the composition may be formulated for administration by injection ( e.g., intraperitoneally, intravenously, subcutaneously, intramuscularly, etc. ). Accordingly, these combinations or these compositions are preferably combined with pharmaceutically acceptable vehicles such as saline, Ringer's solution, dextrose solution, and the like.

The amino acid composition of the invention may comprise a pharmaceutical carrier ( or excipient ). Such a carrier may be any solvent or solid material for encapsulation that is non - toxic. A carrier may give form or consistency, or act as a diluent. Suitable pharmaceutical carriers may include liquid carriers, such as normal saline and other non - toxic salts at or near physiological concentrations, and solid carriers not used for humans, such as talc or sucrose, or animal feed. Carriers may also include stabilizing agents, wetting and emulsifying agents, salts for varying osmolarity, encapsulating agents, buffers, and skin penetration enhancers. Carriers and excipients as well as formulations for parenteral and nonparenteral drug delivery are set forth in Remington's Pharmaceutical Sciences 19th Ed. Mack Publishing ( 1995 ).

For parenteral administration ( including subcutaneous, intradermal, intravenous, intramuscular, and intraperitoneal ), the composition may be an aqueous or an oil based solution. Aqueous solutions may include a sterile diluent such as water, saline solution, a pharmaceutically acceptable polyol such as glycerol, propylene glycol, or other synthetic solvents; an antibacterial and / or antifungal agent such as benzyl alcohol, methyl paraben, chlorobutanol, phenol, thimerosal, and the like; an antioxidant such as ascorbic acid or sodium bisulfite; a chelating agent such as etheylenediaminetetraacetic acid; a buffer such as acetate, citrate, or phosphate; and / or an agent for the adjustment of tonicity such as sodium chloride, dextrose, or a polyalcoholsuch as mannitol or sorbitol. The pH of the aqueous solution may be adjusted with acids or bases such as hydrochloric acid or sodium hydroxide. Oil - based solutions or suspensions may further comprise sesame, peanut, olive oil, or mineral oil.

In a preferred embodiment, the combination of the invention and the amino acid composition of the invention may be administered orally. Non limiting examples of oral formulations that may be used to administer the combination of the invention and the amino acid composition of the invention may be a nutritional formulation, a medical food, a medical beverage, in the form of a complete meal, part of a meal, protein bar, energy bar, or any other bars, as a food additive as a powder for dissolution, in the form of a pharmaceutical formulation such as in the form of a tablet, pill, sachet or capsule or by tube feeding such as by means of nasogastric, nasoduodenal, esophagostomy, gastrostomy, or jejunostomy tubes, or peripheral or total parenteral nutrition. In an exemplary embodiment, the combination of the invention and the compositions of the invention may be administered orally as a dietary supplement.

Compositions for oral administration generally contain inert excipients in addition to the amino acid ingredients of the composition. Oral preparations may be enclosed in capsules or compressed into tablets. Common excipients used in such preparations include pharmaceutically compatible fillers / diluents such as microcrystalline cellulose, hydroxypropyl methylcellulose, starch, lactose, sucrose, glucose, mannitol, sorbitol, dibasic calcium phosphate, or calcium carbonate; binding agents such as alginic acid, carboxymethylcellulose, microcrystalline cellulose, gelatin, gum tragacanth, or polyvinylpyrrolidone; disintegrating agents such as alginic acid, cellulose, starch, or polyvinylpyrrolidone; lubricants such as calcium stearate, magnesium stearate, talc, silica, or sodium stearyl fumarate; glidants such as colloidal silicon dioxide; sweetening agents such as sucrose or saccharin; flavouring agents such as peppermint, methyl salicylate, or citrus flavouring; colouring agents; and preservatives such as antioxidants ( e.g., vitamin A, vitamin C, vitamin E, or retinyl palmitate ), citric acid, or sodium citrate. Oral preparations may also be administered as aqueous suspensions, elixirs, or syrups. For these, the active ingredient may be combined with various sweetening or flavoring agents, coloring agents, and, if so desired, emulsifying and / or suspending agents, as well as diluents such as water, ethanol, glycerin, and combinations thereof.

The combinations of the invention and the compositions of the invention may be nutritionally complete, i.e. may include vitamins, minerals, trace elements as well as nitrogen, carbohydrate and fat and / or fatty acid sources so that they may be used as the sole source of nutrition supplying essentially all the required daily amounts of vitamins, minerals, carbohydrates, fat and / or fatty acids, proteins and the like.

The present invention also provides methods for increasing and/or stimulating muscle protein synthesis, prevention and / or treatment of a loss of any one of muscle mass, muscle strength, muscle function, and physical function, or any combination thereof. The method comprises administering to a subject a composition comprising a plurality of essential amino acids and optionally non - essential amino acids and / or nutrients. Suitable combinations and compositions for administration are described herein.

Another aspect of the present invention provides a method for stimulating muscle protein synthesis, the method comprising administering to a subject the combination of the invention, the composition of the invention or a composition comprising or consisting of the following concentrations of amino acids in terms of w / w % : about 3 to 10,5 % of alanine, about 0 to 2 % of arginine, about 0 to 3 % of asparagine, about 0,5 to 5,5 % of aspartate, about 0 to 2 % of P-alanine, about 0 to 5 % of cysteine, about 0 to 2 % of citrulline, about 1 to 5 % of glutamate, about 15 to 35 % of glutamine, about 3,5 to 9 % of glycine, about 1 to 4 % of histidine, about 0,5 to 2 % of isoleucine, about 0,5 to 4 % of leucine, about 0,5 to 4,5 % of lysine, about 0,1 to 3 % of methionine, about 0 to 7 % of ornithine, about 0,5 to 3 % of phenylalanine, about 0 to 5 % of proline, about 3 to 15 % of serine, about 25 to 45 % of taurine, about 0,5 to 4 % of threonine, about 0 to 2 % of tryptophan, about 0 to 2 % of tyrosine and about 0,5 to 3 % of valine, wherein stimulating muscle protein synthesis is increased compared to a subject not administered said amino acid composition.

According to an embodiment of the method for stimulating muscle protein synthesis, the composition comprises or consists of the following concentrations of amino acids in terms of w / w % : 5,20 % of alanine, 0,9 % of arginine, 1,6 % of asparagine, 2,8 % of aspartate, 0,55 % of P-alanine, 0,9 % of citrulline, 2,4 % of glutamate, 23,65 % of glutamine, 4,55 % of glycine, 2,15 % of histidine, 1 % of isoleucine, 1,9 % of leucine, 2,3 % of lysine, 0,4 % of methionine, 3,55 % of ornithine, 0,8 % of phenylalanine, 7,65 % of serine, 33,45 % of taurine, 2 % of threonine, 1,15 % of tyrosine and 1,1 % of valine.

According to an embodiment of the method for stimulating muscle protein synthesis, the composition further comprises a grape seed extract.

According to another embodiment of the method for stimulating muscle protein synthesis, muscle protein synthesis is improved without physical exercise.

According to another embodiment of the method for stimulating muscle protein synthesis, muscle protein synthesis improves approximately 5 % with a minimum dose of 100 milligrams. According to another embodiment of the method for stimulating muscle protein synthesis, muscle protein synthesis improves approximately 50 % with a minimum dose of 3g.

According to another embodiment of the method for stimulating muscle protein synthesis, a 3 g dose of the composition or the combination is given to a human subject one time a day, two times a day, three times a day, four times a day, five times a day, or six times a day.

According to another embodiment of the method for stimulating muscle protein synthesis, the composition or the combination is administered to a human subject once a day.

According to another embodiment of the method for stimulating muscle protein synthesis, stimulating muscle protein synthesis is increased relative to a subject not administered said amino acid composition with exercise.

Another aspect of the present invention provides a method for stimulating muscle protein synthesis using a dosage up to 50 grams, the method comprising administering to a subject a composition comprising or consisting of the following concentrations of amino acids in terms of w / w % : about 3 to 10,5 % of alanine, about 0 to 2 % of arginine, about 0 to 3 % of asparagine, about 0,5 to 5,5 % of aspartate, about 0 to 2 % of P-alanine, about 0 to 5 % of cysteine, about 0 to 2 % of citrulline, about 1 to 5 % of glutamate, about 15 to 35 % of glutamine, about 3,5 to 9 % of glycine, about 1 to 4 % of histidine, about 0,5 to 2 % of isoleucine, about 0,5 to 4 % of leucine, about 0,5 to 4,5 % of lysine, about 0,1 to 3 % of methionine, about 0 to 7 % of ornithine, about 0,5 to 3 % of phenylalanine, about 0 to 5 % of proline, about 3 to 15 % of serine, about 25 to 45 % of taurine, about 0,5 to 4 % of threonine, about 0 to 2 % of tryptophan, about 0 to 2 % of tyrosine and about 0,5 to 3 % of valine wherein stimulating muscle protein synthesis is increased relative to a subject not administered said amino acid composition.

According to another embodiment of the method for stimulating muscle protein synthesis, stimulating muscle protein synthesis is increased relative to a subject not administered said amino acid composition without exercise. According to another embodiment of the method for stimulating muscle protein synthesis, stimulating muscle protein synthesis is increased relative to a subject not administered said amino acid composition with exercise.

The method of the invention improves and/or stimulates muscle protein synthesis in a subject receiving the combination of the invention or the composition of the invention relative to in a subject that did not receive said amino acid composition. The method of the invention improves and/or stimulates muscle protein synthesis in a subject receiving the combination of the invention or the composition of the invention relative to in a subject that did receive an amino acid composition available on the market for muscle mass increase.

An increase in muscle protein synthesis may be measured by any method known in the art. For example, rates of protein synthesis and breakdown in muscle and blood have been measured for many years using radioactively labeled amino acids or amino acids labeled with stable isotopes. See for example, Yale J Biol Med 1997; 70 ( 1 ) : 65-76, incorporated herein by reference. Measurement of 3 - methyhistidine excretion in urine or arteriovenous difference in 3 - methylhistidine is used as a measure of the unidirectional rate of muscle protein breakdown. Total body skeletal mass can be measured using dual - energy X - ray ( DEXA ) absorptiometry or by CT; see, for example, Am J Clin Nutr 2002; 76 : 378-83, and J Appl Physiol 1985 incorporated herein by reference.

Methods for measuring muscle strength or function are also well known in the art. For example, change in muscle strength and function can be assessed using basic standardized tests as described in B J Nutr 2012; 108 : S88-93 or in Lu et al. ( 2012 ) “ Strength and Functional Measurement for Patients with Muscular Dystrophy ” Muscular Dystrophy, Dr. Madhuri Hegde ( Ed. ), each hereby incorporated by reference.

In some embodiments, a method of the invention may increase muscle protein synthesis by at least 2 - fold. For example, muscle protein synthesis may increase at least 2 - fold, at least 3 - fold, at least 4 - fold, at least 5 - fold, at least 6 - fold, at least 7 - fold, at least 8 - fold, at least 9 - fold, at least 10 - fold or more following administration of the combination of the invention or the composition of the invention. In some embodiments, a method of the invention may increase muscle strength by at least 2 - fold. For example, muscle strength may increase at least 2 - fold, at least 3 - fold, at least 4 - fold, at least 5 - fold, at least 6 - fold, at least 7 - fold, at least 8 - fold, at least 9 - fold, at least 10 - fold or more following administration of the combination of the invention or the composition of the invention. In some embodiments, a method of the invention may increase muscle function by at least 2 - fold. For example, muscle function synthesis may increase at least 2 - fold, at least 3 - fold, at least 4 - fold, at least 5 - fold, at least 6 - fold, at least 7 - fold, at least 8 - fold, at least 9 - fold, at least 10 - fold or more following administration of the combination of the invention or the composition of the invention. In other embodiments, a method of the invention may increase muscle protein synthesis, muscle strength and muscle function, or a combination thereof. Methods for measuring muscle protein synthesis, muscle strength and muscle function are known in the art. and further detailed in the Examples.

In some embodiments, the combination of the invention and the composition of the invention can advantageously be used for the prevention or treatment of a disease or condition involving muscle decline in a mammal, especially an adult mammal. Alternatively, the combination of the invention and the composition of the invention can advantageously be used for the prevention or treatment of a disease or condition selected from the group of sarcopenia, muscle loss, insufficient muscle protein synthesis, muscle degradation, muscle proteolysis, muscle atrophy, muscle dystrophy, muscle catabolism, muscle wasting, loss of muscle strength, loss of muscle mass, loss of muscle function, loss of physical capacity, loss of physical performance, impaired mobility, frailty, surgery, disability, risk of falling and risk of fall - related fractures. Suitable subjects may include a human, a livestock animal, a companion animal, a laboratory animal, or a zoological animal. The combination of the invention and the composition of the invention can advantageously be used to develop muscle for sport or any other reason. In a preferred embodiment, a subject is human. The magnitude of response may depend, in part, on the dose given, the exact combination of amino acids, the physiological condition and / or age of the subject, and / or the timing of administration in relation to performance of exercise.

Preferably, said subject is an adult who wants to develop muscle with or without exercise or an elderly human for the same purpose but also to fight muscle loss with age. In this respect, it is submitted that in the context of this application, an adult is a person of the age 18 or more and an elderly human is a person of the age of 50 years or more, in particular of the age of 55 or more, more in particular of the age of 60 or more, more in particular of the age of 65 or more. This rather broad definition takes into account the fact that the average age varies between different populations, on different continents, etc. Most developed world countries have accepted the chronological age of 65 years as a definition of ‘ elderly ' or older person ( associated with the age at which one may begin to receive pension benefits ), but like many westernized concepts, this does not adapt well to e.g. the situation in Africa. At the moment, there is no United Nations ( UN ) standard numerical criterion, but the UN agreed cut - off is 60+ years to refer to the older population in Western world. The more traditional African definitions of an elder or ‘elderly person correlate with the chronological ages of 50 to 65 years, depending on the setting, the region and the country.

The combination of the invention and the composition of the invention can advantageously be used for the prevention or treatment of muscle decline, in particular loss of muscle mass, during or following body weight maintenance, during or following energy restriction, during or following bed rest or during recovery following physical trauma. In a particularly preferred embodiment, the combination of the invention and the composition of the invention are used in the treatment of a subject, e.g. a subject suffering from overweight or obesity, said subject following a weight loss program, an energy restriction program and / or an exercise program. Said subject may be a child, an adolescent, an adult or an elderly subject. In an embodiment said subject is a child, an adolescent or an adult.

Muscle mass and function are progressively lost with aging, that by age of 60 many otherwise healthy human subjects have reached a threshold where function begins to be affected. In an aspect, administering the combination of the invention or the composition of the invention to any healthy subject may increase muscle protein synthesis, increase muscle strength, increase muscle function, or a combination thereof, though the magnitude of the response may vary depending on age and / or the physiological condition of the subject.

The loss of body protein frequently accompanies illness, whether the illness is short term or long term. In another aspect, administering the combination of the invention or the composition of the invention to a subject that lost body protein as a result of illness may increase muscle protein synthesis, increase muscle strength, increase muscle function, or a combination thereof in the subject. In another aspect, administering the combination of the invention or the composition of the invention to a subject at risk of or experiencing muscle atrophy may increase muscle protein synthesis, increase muscle strength, increase muscle function, or a combination thereof. Non - limiting examples of subjects at risk of or experiencing muscle atrophy include humans with a sedentary lifestyle, people with seated jobs, medical conditions that limit movement, subjects that are bedridden, subjects who are away from Earth's gravity, subjects with an injury to a nerve that connects to muscle, and subjects at risk for diagnosed with a disease affecting the nerves that control muscles. Non - limiting examples of diseases, disorders or conditions in which muscle atrophy occurs includes polio, Guillan - Barre syndrome, chronic obstructive pulmonary disease, congestive heart failure, acute coronary syndrome, chronic heart failure, cardiac cachexia, cancer, sarcopenia, spinal cord injury, osteoarthritis, arthritis, stroke, malnutrition, muscular dystrophy ( e.g. Becker, congenital, Duchenne, Distal, Emery - Dreifuss, Facioscapulohumeral, Limb Girdle, Oculopharyngeal ), spinal muscular atrophy ( e.g. ALS, motor neuron disease, infantile progressive spinal muscular atrophy, intermediate spinal muscular atrophy, juvenile spinal muscular atrophy, adult spinal muscularatrophy ), inflammatory myopathies ( e.g. dermatomyositis, polymyositis ), diseases of the peripheral nerve ( e.g. Carcot Marie tooth disease, Dejerine - Sottas disease, Friedreich's ataxia ), diseases of the neuromuscular junction ( Myasthenia gravis, Lambert - Eaton syndrome ), metabolic diseases of the muscle ( acid maltase deficiency, carnitine deficiency, carnitine palm ityl transferase deficiency, Debrancer enzyme deficiency, Lactate dehydrogenase deficiency, Mitochon drial deaminase deficiency, Phophorylase deficiency, Phosphofructokinase deficiency, Phosphoglycerate kinase deficiency ), other myopathies ( central disease, hyperthyroid myopathy, myotonia congenita, myotubular myopathy, paramytonia congenita, periodic paralysis - hypokalemic - hyperkalemic ), or any other disease or condition that requires a subject to be immobilized or on bed rest, especially chronic heart failure and cardiac cachexia.

According to an embodiment of the method for reducing muscle fatigue and/or increasing muscle performance, said muscle fatigue is exercise-induced muscle fatigue or posture-induced muscle fatigue.

According to another embodiment of the method for reducing muscle fatigue and/or increasing muscle performance, the subject is mammal, preferably a human. According to another embodiment of the method for reducing muscle fatigue and/or increasing muscle performance, the muscle is a skeletal muscle.

As defined herein, the terms "muscle fatigue" and "skeletal muscle fatigue" occur when these muscles cannot exert normal force, or when more effort than normal is required to achieve a desired level of force. Muscle fatigue may include but is not limited to exercise-induced muscle fatigue, posture induced muscle fatigue. Exercise-induced muscle fatigue may occur during and after exercise. Muscle fatigue may be decreased by retarding the onset and/or duration of muscle fatigue. When skeletal muscles are induced to contract repeatedly there is a progressive loss in their ability to generate a target force or power. This condition is known simply as fatigue. In particular, muscle fatigue may include, but is not limited to, muscle pain attributed to strenuous exercise, lassitude in the arms and legs resulting from acute exercise and lower back pain and stiffness in the shoulders due to holding a fixed posture over a prolonged period of time. In particular, muscle fatigue can result in an incapacity to maintain and/or repeat a physical effort.

In some embodiments, the exercise-induced muscle fatigue is due to prolonged exercise or high- intensity exercise.

As defined herein, the term "increasing (skeletal) muscle performance" means, for example, increasing muscle strength, increasing muscle endurance and in particular increasing the ability to sustain athletic muscle force and/or work during muscle exercise and/or physical effort.

Another aspect of the present invention provides a method for improving muscle recovery after exercise in a subject, the method comprising administering to the subject the composition of the invention or the combination of the invention. Typically, improving muscle recovery after exercise relates to accelerating muscle recovery and reducing the time needed for muscles to recover.

In some embodiments, by "muscle recovery" is meant the recovery from spontaneous muscle contractions and fatigue following exercise that may or may not be associated with the development of frank cramps. According to an embodiment of the method for improving muscle recovery after exercise, the subject is mammal, preferably a human.

According to another embodiment of the method for improving muscle recovery after exercise, the muscle recovery is muscle recovery after exercise, post-workout muscle recovery or muscle recovery after a physical effort.

According to another embodiment of the method for improving muscle recovery after exercise, the muscle is a skeletal muscle.

The methods of the invention generally comprises administering the combination of the invention and the composition of the invention to a subject. Suitable subjects include animals such as mammals and humans. Non - limiting examples of suitable animals include companion animal such as cats, dogs, rodents, and horses; research animal such as mice, rats and other rodents; agricultural animal such as cows, cattle, pigs, goats, sheep, horses, deer, chickens and other fowl; zoo animal; and primates such as chimpanzees, monkeys, and gorillas. In a preferred embodiment, the subject is a human. In another preferred embodiment, the subject is a mammal.

The frequency of administration may be once, twice, three times or more daily, or once, twice, three times or more per week or per month, as needed as to produce the desired effect. The amount administered to the subject can and will vary depending upon the subject ( e.g. age, weight, health status ), and the particular mode of administration. Those skilled in the art will appreciate that dosages may also be determined with guidance from Goodman & Goldman's The Pharmacological Basis of Therapeutics, Tenth Edition ( 2001 ), Appendix II, pp. 475-493, and the Physicians ' Desk Reference.

The human subject may be of any age, a baby, an infant, a child, an adolescent, an adult or an elderly. In some embodiments, the human subject may be about 6 months, 12 months, 18 months, 24 months, 3 years, 4, 5 ,10, 15, 18, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 years of age or older. In some embodiments, the human subject is a baby from 6 months to 12 months. In some embodiments, the human subject is an infant and may be about 12 to 36 months. In yet other embodiments the human subject is a child from 3 years to 12 years. In yet other embodiments the human subject is an adolescent from 12 years to 18 years. In some preferred embodiments, the human subject is an adult of 18 years of age or older. In other preferred embodiments, the human subject is 20 years of age or older. In other preferred embodiments, the human subject is 25 years of age or older. In other preferred embodiments, the human subject is 30 years of age or older. In other preferred embodiments, the human subject is 35 years of age or older. In other preferred embodiments, the human subject is 40 years of age or older. In other preferred embodiments, the human subject is 45 years of age or older. In yet other preferred embodiments, the human subject is 50 years of age or older. In still other preferred embodiments, the human subject is 55 years of age or older. In other preferred embodiments, the human subject is 60 years of age or older. In yet other preferred embodiments, the human subject is 65 years of age or older. In still other preferred embodiments, the human subject is 70 years of age or older. In other preferred embodiments, the human subject is 75 years of age or older. In still other preferred embodiments, the human subject is 80 years of age or older. In yet other preferred embodiments, the human subject is 85 years of age or older. In still other preferred embodiments, the human subject is 90 years of age or older. In still other preferred embodiments, the human subject is 100 years of age or older.

In some embodiments, the subject may be an alternative of the embodiments for subjects that lack daily exercise.

In other embodiments, the subject may be an alternative of the embodiments for subjects that lack the ability to efficiently stimulate muscle protein synthesis.

In other embodiments, the subject may be recovering from lack of physical exercise. During high - intensity muscular physical exercises, the rate of muscular work being performed may exceed the ability of the blood supply to deliver oxygen, creating a condition which induces reductive stress in muscle cells and may lead to muscle damage, impaired performance, predisposition to injury and a prolonged recovery period. Non - limiting examples of physical exercises that may lead to muscle damage, impaired performance, predisposition to injury and a prolonged recovery period may include flexibility exercises such as stretching, aerobic exercises such as cycling, swimming, walking, skipping rope, rowing, running, hiking or playing tennis, anaerobic exercises, such as weight training, functional training, eccentric training or sprinting, strength training, agility training, or eccentric training.

Some advantages of the composition of the invention or the combination of the invention is that they (1) provide better activity compared to existing amino acid compositions, (2) lessen and/or reduce side effects, such as nausea, that may occur in a subject compared to existing amino acid compositions and (3) provide increased shelf-life of composition and combination.

Also provided are kits. Such kits can include the combination of the invention or the composition of the invention and, in certain embodiments, instructions for administration. Such kits can facilitate performance of the methods of the invention described herein. When supplied as a kit, the different components of the combination or the composition can be packaged in separate containers and admixed immediately before use. Components include, but are not limited to an amino acid composition, as described herein. Such packaging of the components separately can, if desired, be presented in a pack or dispenser device which may contain one or more unit dosage forms containing the composition. The pack may, for example, comprise metal or plastic foil such as a blister pack. Such packaging of the components separately can also, in certain instances, permit long - term storage without losing activity of the components.

Kits may also include reagents in separate containers such as, for example, sterile water or saline to be added to a lyophilized active component packaged separately. For example, sealed glass ampules may contain a lyophilized component and in a separate ampule, sterile water, sterile saline or sterile each of which has been packaged under a neutral non - reacting gas, such as nitrogen. Ampules may consist of any suitable material, such as glass, organic polymers, such as polycarbonate, polystyrene, ceramic, metal or any other material typically employed to hold reagents. Other examples of suitable containers include bottles that may be fabricated from similar substances as ampules, and envelopes that may consist of foil - lined interiors, such as aluminum or an alloy. Other containers include test tubes, vials, flasks, bottles, syringes, and the like. Containers may have a sterile access port, such as a bottle having a stopper that can be pierced by a hypodermic injection needle. Other containers may have two compartments that are separated by a readily removable membrane that upon removal permits the components to mix. Removable membranes may be glass, plastic, rubber, and the like.

In certain embodiments, kits can be supplied with instructional materials. Instructions may be printed on paper or other substrate, and / or may be supplied as an electronic readable medium, such as a floppy disc, mini - CD - ROM, CD - ROM, DVD - ROM, Zip disc, videotape, audio tape, and the like. Detailed instructions may not be physically associated with the kit; instead, a user may be directed to an Internet web site specified by the manufacturer or distributor of the kit. Those skilled in the art will appreciate that the invention described herein is susceptible to variations and modifications other than those specifically described. It is to be understood that the invention includes all such variations and modifications without departing from the spirit or essential characteristics thereof. The invention also includes all of the steps, features, compositions and compounds referred to or indicated in this specification, individually or collectively, and any and all combinations or any two or more of said steps or features. The present disclosure is therefore to be considered as in all aspects illustrated and not restrictive, the scope of the invention being indicated by the appended claims, and all changes which come within the meaning and range of equivalency are intended to be embraced therein.

The foregoing description will be more fully understood with reference to the following Examples. Such Examples, are, however, exemplary of methods of practising the present invention and are not intended to limit the application and the scope of the invention.

EXAMPLES

The following examples are included to demonstrate various embodiments of the present disclosure. It should be appreciated by those of skill in the art that the techniques disclosed in the examples that follow represent techniques discovered by the inventors to function well in the practice of the invention, and thus can be considered to constitute preferred modes for its practice. However, those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the spirit and scope of the invention.

Example 1. Experimental Evidence for an Effect of a 3 g Mixture of FXAA versus a placebo and a commercial product containing amino acids for the same purpose (muscle growth) but in another proportion.

The following study was performed to quantify the responses to one and three doses of 3g, of the following amino acid formulation: 5,20 % of alanine, 0,9 % of arginine, 1,6 % of asparagine, 2,8 % of aspartate, 0,55 % of P-alanine, 0,9 % of citrulline, 2,4 % of glutamate, 23,65 % of glutamine, 4,55 % of glycine, 2,15 % of histidine, 1 % of isoleucine, 1,9 % of leucine, 2,3 % of lysine, 0,4 % of methionine, 3,55 % of ornithine, 0,8 % of phenylalanine, 7,65 % of serine, 33,45 % of taurine, 2 % of threonine, 1,15 % of tyrosine and 1,1 % of valine. The acute stimulation of muscle protein synthesis resulting from the ingestion of either 3g or 9g of the amino acid formulation described above was determined in a group of older subjects ( see Table A ). The dose of 3 g was chosen because of the commercial viability of this dosage, based on both cost and regulations. The response to 3 g was compared to a dosage of 9 g, since the higher dosages has been shown to not only stimulate muscle protein FSR, but to result in long - term outcome benefits in terms of strength and physical function ( 13 ). Muscle protein synthesis was determined before and after oral ingestion of the amino acid formulation. The same was compared with a placebo of 3 and 9g of maltodextrin.

Subjects were studied following an overnight fast. The study procedure involved a 5 hr. fasted period and a 3 hr. period after ingestion of the FXAA formula. Subjects were given a constant infusion of tracer amounts of 2H3 - phenyl alanine throughout the entire experiment. Muscle biopsies were taken after 2 and 5 hours of tracer infusion in the basal period, and at three hours after ingestion of the amino acid formula. Muscle free and protein bound phenylalanine enrichments were determined on each biopsy sample, and the fractional synthetic rate ( FSR ) of muscle protein calculated in the basal state and over the 3 hours after ingestion of the formula. Muscle protein FSR reflects the fraction of the total muscle that is produced in a unit of time ( per hour in this experiment ). Since in such a short period of time as this experiment there is no possibility that the amount of muscle protein changed from the beginning to the end of the study, muscle protein FSR is a direct reflection of the absolute rate of muscle protein synthesis. Values were calculated as the post value pre value. In this way each subject served as their own control, as it has been shown in a variety of studies that the fasting muscle protein synthesis does not change in the time - frame of this study ( eg, 14 ). The post ingestion value represents the integrated response of the entire 3 hours after ingestion of the formulation of amino acids. Muscle FSR increased 0.0568 % / h following ingestion of the 3 g dosage. This was a 57 % increase above the basal FSR. The corresponding value was an increase of 0.0692 % / h, which was a 76 % increase over the basal value. Plasma FXAA levels were also measured. The placebo has shown no improvement in the muscle either at 3g or 9g. The competition products have shown results significantly less good.

* Increase over corresponding basal value, area under curve ** BCAAs are the branched chain amino acids leucine, valine, and isoleucine

*** It has been taken in consideration the net weight of amino acid in order to compare with our invention. Here as the proportion of amino acid is 26% in the commercial product it has been given to the subjects 11,54 g of product as an equivalent of 3 g of pure amino acids and 34,60g as an equivalent to 9 g

The results are unexpected due to the low dosage of this optimized ratio of FXAA for stimulation of muscle protein synthesis. A Typical protein containing amino acids would require a dosage of well over 20 grams to have a much lower effect than 3 grams of this composition.

Claims

1. An amino acid composition comprising the following amino acids: alanine, arginine, asparagine, aspartate, P-alanine, cysteine, citrulline, glutamate, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, ornithine, phenylalanine, proline, serine, taurine, threonine, tryptophan, tyrosine and valine that stimulates muscle protein synthesis more than 50 % at dosages up to 50 grams with or without exercise.

2. The amino acid composition of claim 1 comprising the following concentrations of amino acids in terms of w / w % : about 3 to 10,5 % of alanine, about 0 to 2 % of arginine, about 0 to 3 % of asparagine, about 0,5 to 5,5 % of aspartate, about 0 to 2 % of P-alanine, about 0 to 5 % of cysteine, about 0 to 2 % of citrulline, about 1 to 5 % of glutamate, about 15 to 35 % of glutamine, about 3,5 to 9 % of glycine, about 1 to 4 % of histidine, about 0,5 to 2 % of isoleucine, about 0,5 to 4 % of leucine, about 0,5 to 4,5 % of lysine, about 0,1 to 3 % of methionine, about 0 to 7 % of ornithine, about 0,5 to 3 % of phenylalanine, about 0 to 5 % of proline, about 3 to 15 % of serine, about 25 to 45 % of taurine, about 0,5 to 4 % of threonine, about 0 to 2 % of tryptophan, about 0 to 2 % of tyrosine and about 0,5 to 3 % of valine.

3. A combination comprising an amino acid composition and a P-alanine composition, for simultaneous, separate or sequential administration, wherein the amino acid composition comprises (w/w %): about 3 to 10,5 % of alanine, about 0 to 2 % of arginine, about 0 to 3 % of asparagine, about 0,5 to 5,5 % of aspartate, about 0 to 5 % of cysteine, about 0 to 2 % of citrulline, about 1 to 5 % of glutamate, about 15 to 35 % of glutamine, about 3,5 to 9 % of glycine, about 1 to 4 % of histidine, about 0,5 to 2 % of isoleucine, about 0,5 to 4 % of leucine, about 0,5 to 4,5 % of lysine, about 0,1 to 3 % of methionine, about 0 to 7 % of ornithine, about 0,5 to 3 % of phenylalanine, about 0 to 5 % of proline, about 3 to 15 % of serine, about 25 to 45 % of taurine, about 0,5 to 4 % of threonine, about 0 to 2 % of tryptophan, about 0 to 2 % of tyrosine and about 0,5 to 3 % of valine, and wherein the P-alanine composition comprises about 0.1 to 2 % of P-alanine and is formulated for the sustained release of P-alanine.

4. The amin acid composition of any one of claims 1-2 or the combination of claim 3, wherein the amino acids composition further comprises a grape seed extract. 5. A method for stimulating muscle protein synthesis, the method comprising administering to a subject the combination of claim 3 or 4, or a composition comprising the following concentrations of amino acids in terms of w / w % : about 3 to 10,5 % of alanine, about 0 to 2 % of arginine, about 0 to 3 % of asparagine, about 0,5 to 5,5 % of aspartate, about 0 to 2 % of P-alanine, about 0 to 5 % of cysteine, about 0 to 2 % of citrulline, about 1 to 5 % of glutamate, about 15 to 35 % of glutamine, about 3,5 to 9 % of glycine, about 1 to 4 % of histidine, about 0,5 to 2 % of isoleucine, about 0,5 to 4 % of leucine, about 0,5 to 4,5 % of lysine, about 0,1 to 3 % of methionine, about 0 to 7 % of ornithine, about 0,5 to 3 % of phenylalanine, about 0 to 5 % of proline, about 3 to 15 % of serine, about 25 to 45 % of taurine, about 0,5 to 4 % of threonine, about 0 to 2 % of tryptophan, about 0 to 2 % of tyrosine and about 0,

5 to 3 % of valine, wherein stimulating muscle protein synthesis is increased compared to a subject not administered said amino acid composition.

6. The method of claim 5, wherein muscle protein synthesis is improved without physical exercise.

7. The method of claim 5 or 6, wherein the subject is a mammal, preferably a human.

8. The method of claim 5 or 6, wherein the subject is a human of any age, a baby, an infant, a child, an adolescent, an adult or an elderly from 6 months age or older.

9. The method of any one of claims 5-8, wherein muscle protein synthesis improves approximately 5 % with a minimum dose of 100 milligrams.

10. The method of any one of claims 5-8, wherein muscle protein synthesis improves approximately 50 % with a minimum dose of 3 grams.

11. The method of any one of claims 5-10, wherein the composition comprises the following concentrations of amino acids in terms of w / w % : 5,20 % of alanine, 0,9 % of arginine, 1,6 % of asparagine, 2,8 % of aspartate, 0,55 % of P-alanine, 0,9 % of citrulline, 2,4 % of glutamate, 23,65 % of glutamine, 4,55 % of glycine, 2,15 % of histidine, 1 % of isoleucine, 1,9 % of leucine, 2,3 % of lysine, 0,4 % of methionine, 3,55 % of ornithine, 0,8 % of phenylalanine, 7,65 % of serine, 33,45 % of taurine, 2 % of threonine, 1,15 % of tyrosine and 1,1 % of valine.

12. The method of any one of claims 5-11, wherein the composition further comprises a grape seed extract.

13. The method of claim 10 or 11, wherein a 3 g dose of the composition or the combination is given to a human subject one time a day, two times a day, three times a day, four times a day, five times a day, or six times a day.

14. The method of claim 9, wherein up to 50 g dose of the composition is administered to a human subject once a day.

15. The method of any one of clams 5-14, wherein stimulating muscle protein synthesis is increased relative to a subject not administered said amino acid composition with exercise.

16. A method for stimulating muscle protein synthesis using a dosage up to 50 grams, the method comprising administering to a subject a composition comprising the following concentrations of amino acids in terms of w / w % : about 3 to 10,5 % of alanine, about 0 to 2 % of arginine, about 0 to 3 % of asparagine, about 0,5 to 5,5 % of aspartate, about 0 to 2 % of P-alanine, about 0 to 5 % of cysteine, about 0 to 2 % of citrulline, about 1 to 5 % of glutamate, about 15 to 35 % of glutamine, about 3,5 to 9 % of glycine, about 1 to 4 % of histidine, about 0,5 to 2 % of isoleucine, about 0,5 to 4 % of leucine, about 0,5 to 4,5 % of lysine, about 0,1 to 3 % of methionine, about 0 to 7 % of ornithine, about 0,5 to 3 % of phenylalanine, about 0 to 5 % of proline, about 3 to 15 % of serine, about 25 to 45 % of taurine, about 0,5 to 4 % of threonine, about 0 to 2 % of tryptophan, about 0 to 2 % of tyrosine and about 0,5 to 3 % of valine, wherein stimulating muscle protein synthesis is increased relative to a subject not administered said amino acid composition.

17. The method of claim 16, wherein stimulating muscle protein synthesis is increased relative to a subject not administered said amino acid composition without exercise.

18. The method of claim 17, wherein stimulating muscle protein synthesis is increased relative to a subject not administered said amino acid composition with exercise.

19. A method for reducing muscle fatigue and/or increasing muscle performance in a subject, the method comprising administering to the subject the composition of claim 1, 2 or 4, or the combination of claim 3 or 4.

20. The method according to claim 19, wherein said muscle fatigue is exercise-induced muscle fatigue or posture-induced muscle fatigue.

21. The method of any one of claims 19-209, wherein the subject is mammal, preferably a human.

22. The method of any one of claims 19-21, wherein the muscle is a skeletal muscle.

23. A method for improving muscle recovery after exercise in a subject, the method comprising administering to the subject the composition of claim 1, 2 or 4, or the combination of claim 3 or 4.

24. The method of claim 23, wherein the subject is mammal, preferably a human.

25. The method of any one of claims 23-24, wherein the muscle recovery is muscle recovery after exercise, post-workout muscle recovery or muscle recovery after a physical effort.

26. The method of any one of claims 23-25, wherein the muscle is a skeletal muscle.