Compositions and methods for treating muscle wasting associated with kidney disease or kidney dysfunction

Abstract

The composition comprises at least two ingredients selected from the group consisting of fish oil, L-arginine, vitamin E, vitamin C, vitamin B3, vitamin B5, vitamin B6, vitamin B1, vitamin B2, folic acid, biotin, and vitamin B12, and is formulated for use in the prevention and / or treatment of a disease or condition associated with muscle wasting in a subject in need thereof. The method can achieve at least one result of preventing and / or treating a disease or condition associated with muscle wasting in a subject at risk of or suffering from renal failure, renal dysfunction, or / and renal disease. The composition and method can be used to improve the level of at least one amino acid.

Description

[Technical Field]

[0001] The present disclosure relates generally to compositions and methods for preventing and / or treating diseases or conditions associated with muscle wasting, particularly in subjects at risk for or suffering from renal failure, impaired renal function, or / and renal disease, such as chronic kidney disease, protein-energy wasting (PEW), end-stage renal disease, renal failure due to intensive care unit admission, acute kidney injury, and the like.

[0002] [Background technology] Renal failure, renal dysfunction, or / and kidney disease, such as chronic kidney disease (CKD), PEW, end-stage renal disease (ESRD), renal failure due to intensive care unit (ICU) admission, and acute kidney injury (AKI), can lead to a constant excessive loss of some amino acids (AA).

[0003] Amino acids are the structural protein building blocks of muscle, and a constant loss and / or insufficient amount of amino acids results in increased protein breakdown and decreased protein synthesis, leading to loss of muscle mass and muscle wasting.

[0004] Thus, muscle wasting is a common complication of kidney and / or renal disease, characterized by loss of muscle mass, strength, and function, which significantly increases the risk of morbidity and mortality in this population.

[0005] Nutritional recommendations are typically aimed at overall improvement of muscle wasting, but no data exist regarding preventing and / or treating muscle wasting conditions or diseases associated with renal failure, renal dysfunction, or renal disease.

[0006] Thus, there is a need to identify nutrients necessary to prevent and / or treat muscle wasting conditions or diseases associated with renal failure, renal dysfunction, or renal disease.

[0007] Additionally, there is a need to provide nutritional compositions and methods for preventing and / or treating diseases or conditions associated with muscle wasting, particularly in subjects at risk for or suffering from renal failure, renal impairment, or / and renal disease, such as CKD, PEW, end-stage renal disease (ESRD), renal failure due to ICU admission, acute kidney injury (AKI), etc.

[0008] [Problem to be solved by the invention] The object of the present invention is to provide a method for the prevention and / or treatment of muscle wasting conditions or diseases associated with renal failure, renal dysfunction or renal disease, in particular, muscle wasting conditions or diseases associated with, for example, CKD, PEW, ESRD, renal failure due to ICU admission, AKI, etc., and an optimal nutritional composition having specific ingredients for said prevention and / or treatment.

[0009] [Summary of the Invention] Preclinical studies disclosed herein demonstrate that ingesting a nutritional composition according to the present invention prevents the loss of important amino acids for muscle protein biosynthesis, and therefore prevents muscle mass loss and muscle wasting in subjects with renal failure, impaired renal function, or disease.

[0010] Benefits from this improvement include the prevention and / or treatment of kidney disease or muscle wasting conditions or diseases associated with kidney disease.

[0011] Accordingly, the present disclosure generally relates to novel compositions and methods for preventing and / or treating diseases or conditions associated with muscle wasting, particularly in subjects at risk for or suffering from renal failure, renal impairment, or / and renal disease, such as CKD, PEW, ESRD, renal failure due to ICU admission, AKI, etc.

[0012] Additional features and advantages are described herein, and will be apparent from the drawings and detailed description that follow. [Brief explanation of the drawings]

[0013] [Figure 1a] 1 is a graph showing results from an example experiment disclosed herein demonstrating a reduction in urinary leucine levels when fed a nutritional composition. [Figure 1b] 1 is a graph showing results from an example experiment disclosed herein demonstrating no significant change in plasma leucine levels when fed a nutritional composition. [Figure 2a] 1 is a graph showing results from an example experiment disclosed herein demonstrating a reduction in urinary lysine levels when fed a nutritional composition. [Figure 2b] 1 is a graph showing results from an example experiment disclosed herein demonstrating no significant change in plasma lysine levels when fed a nutritional composition. [Figure 3a] 1 is a graph showing results from an example experiment disclosed herein demonstrating increased urinary arginine levels when fed a nutritional composition. [Figure 3b] 1 is a graph showing results from an example experiment disclosed herein demonstrating increased plasma arginine levels when fed a nutritional composition. [Figure 4a] 1 is a graph showing results from an example experiment disclosed herein demonstrating reduced urinary methionine levels when fed a nutritional composition. [Figure 4b] 1 is a graph showing results from an example experiment disclosed herein demonstrating a decrease in plasma methionine levels when fed a nutritional composition. [Figure 5] 1 is a graph showing results from an example experiment disclosed herein demonstrating a trend toward decreased urinary glutamine levels when fed a nutritional composition.

[0014] [Mode for Carrying Out the Invention] definition Some definitions are provided below. However, definitions may be found in the "Embodiments" section below, and the heading "Definitions" above does not imply that such disclosure in the "Embodiments" section is not a definition.

[0015] In the context of the present invention, the expression "nutritional composition" refers to a composition that provides nutrition to a subject. This nutritional composition is usually taken enterally, orally, parenterally or intravenously. Preferably, the nutritional composition is for oral use.

[0016] Furthermore, "nutritional composition" may refer to a liquid, powder, gel, paste, solid, concentrate, suspension, or ready-to-use form of enteral formula, oral formula, infant formula, pediatric formula, adult formula, porridge and / or cereal, food product, food composition, baby food, or pet food. The compositions of the present disclosure, including many of the embodiments described herein, may comprise, consist of, or consist essentially of any additional or optional ingredients, components, or limitations described herein or otherwise useful in dietary therapy, in addition to the essential elements and limitations described herein. Food products according to the present invention include, but are not limited to, bread, cake, cookies, crackers, extruded snacks, potato products, rice products, corn products, wheat products, dairy products, yogurt, confectionery, hard candy, gummy candy, nutritional bars, breakfast cereals, or beverages, such as juices, smoothies, plant-based beverages, including, for example, soy milk, rice milk, or almond milk.

[0017] "Prevention" includes reducing the risk and / or severity of a condition or disease. The terms "treatment," "treat," and "to alleviate" include both prophylactic or preventive treatment (which prevent and / or delay the onset of the targeted condition or disorder) and curative, therapeutic, or disease-modifying treatment, including therapeutic measures that cure, delay, attenuate the symptoms, and / or halt the progression of a diagnosed condition or disease; and include treatment of patients who are ill or diagnosed as suffering from a disease or medical condition, as well as treatment of patients at risk of or suspected of having the disease. The term does not necessarily imply that a subject is treated to the point of cure. The terms "treatment" and "treating" also refer to maintaining and / or improving the health of individuals who are not afflicted with the disease but who may be susceptible to an ill health condition. The terms "treatment / therapy," "treat / treating," and "alleviating" are also intended to include synergistic or otherwise potentiating effects of one or more primary preventative or therapeutic measures. The terms "treatment / therapy," "treat / treating," and "alleviating" are further intended to include dietary management of a disease or condition, or dietary management for the prophylaxis or prevention of a disease or condition. Treatment may be patient-related or physician-related.

[0018] An "individual" is a mammal, preferably a human, a livestock animal, or a pet. In particular, the term "livestock animal" may include, but is not limited to, a horse (e.g., a pet or horse receiving medical treatment), or a cow or poultry (e.g., a cow or poultry used in agriculture). In particular, the term "pet" refers to any animal that can benefit from or enjoy the compositions provided by the present disclosure. For example, a pet may be an animal such as a bird, bovine, canine, equine, feline, caprine, wolf, murine, ovine, or porcine, although a pet may be any suitable animal.

[0019] All percentages set forth herein are by weight of the total composition unless otherwise specified. As used herein, "about," "approximately," and "substantially" are understood to refer to numbers within a range of numerical values, e.g., within -10% to +10% of the referenced number, preferably within -5% to +5% of the referenced number, more preferably within -1% to +1% of the referenced number, and most preferably within -0.1% to +0.1% of the referenced number. All numerical ranges herein should be understood to include all integers or fractions within that range. Furthermore, these numerical ranges should be interpreted as supporting claims directed to any number or subset of numbers within that range. For example, a disclosure of 1 to 10 should be interpreted as corresponding to ranges of 1 to 8, 3 to 7, 1 to 9, 3.6 to 4.6, 3.5 to 9.9, etc.

[0020] As used in this disclosure and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context dictates otherwise. Thus, for example, reference to "a component" or "the component" includes two or more components.

[0021] The terms "comprise," "comprises," and "comprising" should be construed as inclusive rather than exclusive. Similarly, the terms "include," "including," and "or" should all be construed as inclusive unless such interpretation is clearly prevented by the context. However, the compositions disclosed herein may exclude elements not specifically disclosed herein. Thus, disclosure of an embodiment using the term "comprising" includes disclosure of embodiments "consisting essentially of" and "consisting of" the specified component. A composition or unit dosage form "consisting essentially of" means that the referenced component comprises at least 50% by weight, preferably at least 75% by weight, more preferably at least 85% by weight, and most preferably at least 95% by weight of the referenced component.

[0022] The term "and / or" used in the context of "X and / or Y" should be interpreted as "X" or "Y" or "X and Y". Similarly, "at least one of X or Y" should be interpreted as "X" or "Y" or "X and Y". For example, "muscle loss and / or renal dysfunction" should be interpreted as "muscle loss" or "renal dysfunction" or "both muscle loss and renal dysfunction".

[0023] As used herein, the terms "examples" and "such as," particularly when followed by a list of terms, are merely exemplary and illustrative and should not be considered exclusive or inclusive. As used herein, a condition "associated with" or "linked with" another condition means that the conditions occur simultaneously, preferably that the conditions are caused by the same underlying condition, and most preferably that one of the specified conditions is caused by the other specified condition.

[0024] "Chronic kidney disease (CKD)" refers to kidney damage (i.e., albuminuria) or reduced kidney function (i.e., GFR <60 mL / min / 1.73 m), regardless of clinical diagnosis. 2 ) for more than 3 months. CKD is defined as a blood pressure of 90 mL / min / 1.73 m 2 Ultra (stage 1), 60–89 mL / min / 1.73 m 2 (Stage 2), 30–59 mL / min / 1.73 m 2 (Stage 3), 15–29 mL / min / 1.73 m 2 (Stage 4), and 15 mL / min / 1.73 m 2 Chronic kidney disease is classified into five stages based on GFR, with a GFR of 60-89 mL / min / 1.73 m (stage 1) and less than 5 (stage 2). 2 (Stage 2), 30–59 mL / min / 1.73 m 2 (Stage 3) includes stage 2 and stage 3 chronic kidney disease based on GFR. Preferably, "early stage chronic kidney disease" is defined as a GFR of 60 to 89 mL / min / 1.73 m 2 This includes stage 2 chronic kidney disease based on a GFR of 15-29 mL / min / 1.73 m. Late stage chronic kidney disease is defined as a GFR of 15-29 mL / min / 1.73 m. 2 (Stage 4), and 15 mL / min / 1.73 m 2 Stage 4 and Stage 5 chronic kidney disease based on a GFR of less than 15-29 mL / min / 1.73 m 2 This includes stage 4 chronic kidney disease based on GFR.

[0025] "End-stage renal disease (ESRD)" includes the condition of an individual with CKD who requires renal replacement therapy. Preferably, ESRD is defined as a blood flow rate of 15 mL / min / 1.73 m 2 Includes stage 5 chronic kidney disease based on a GFR of less than 0.05.

[0026] "Muscle wasting" involves a prolonged catabolic state in which muscle protein breakdown exceeds the rate of protein synthesis.

[0027] "Protein-energy wasting (PEW)" refers to a decrease in body protein mass and fuel reserves in a subject due to maladaptive metabolic conditions, including nonspecific inflammatory processes, transient intercurrent catabolic disorders, nutrient loss into the dialysate, acidemia, endocrine disorders such as insulin resistance, growth hormone resistance, and insulin-like growth factor-1 resistance, hyperglucagonemia, hyperparathyroidism, and blood loss into the hemodialyzer, feces, or via blood draws.

[0028] As used herein, an "effective amount" is an amount that prevents a deficiency, treats a disease or medical condition in an individual, or more generally, alleviates symptoms, manages the progression of a disease, or provides a nutritional, physiological, or medical benefit to an individual. The relative terms "improved," "increased," "enhanced," and the like refer to the effect of the compositions disclosed herein.

[0029] As used herein, "RPB" blends shall be as defined in Table 1 below.

[0030] [Table 1]

[0031] Embodiment In human tissues, especially muscle, amino acid residues are the second largest building block, with water being the only largest building block.

[0032] Subjects with renal failure and / or kidney disease, such as chronic kidney disease, PEW, end-stage renal disease, kidney failure due to intensive care unit admission, acute kidney injury, etc., have been shown to have elevated levels of certain AAs in the urine, which means that the human organism experiences a significant and constant loss of these AAs, resulting in impaired uptake of these AAs into muscle or impaired muscle protein synthesis, leading to muscle wasting, including loss of muscle mass and muscle wasting.

[0033] One of the most common diseases that leads to muscle wasting is CKD. In CKD, the kidneys gradually lose their ability to excrete waste products, concentrate urine, reabsorb protein and AA, and conserve electrolytes. Unlike AKI, in which kidney function is rapid but reversible, kidney function in CKD irreversibly progresses and deteriorates toward ESRD. CKD results from heterogeneous disease pathways that irreversibly alter kidney function and structure over months or years.

[0034] The main causes of CKD are diabetes and hypertension, therefore the study was related to diabetic subjects.

[0035] The present inventors have surprisingly identified certain nutrients that reduce the urinary levels of certain AA, such as leucine, lysine, methionine, and glutamine, and increase arginine.Considering that these AA cannot be synthesized by the human body and can only be obtained through supplementation, it is extremely important to maintain the level of these AA in blood and prevent the body from losing these AA due to kidney dysfunction and / or kidney disease.The reduction of the specified AA in urine means preventing the subject's body from losing these AA and maintaining a sufficient level of these AA for muscle protein biosynthesis, thus preventing and / or treating diseases or conditions related to muscle wasting.

[0036] Thus, in a first embodiment, the present invention relates to a nutritional composition for use in the prevention and / or treatment of a disease or condition associated with muscle wasting in a subject in need thereof, the nutritional composition comprising: fish oil, L-arginine, Vitamin E, Vitamin C, Vitamin B3, Vitamin B5, Vitamin B6, Vitamin B1, Vitamin B2 folic acid, biotin, Vitamin B12.

[0037] Fish oil generally contains 5% by weight or more, preferably 10% by weight or more, of DHA.

[0038] L-arginine can be naturally occurring or synthetic.

[0039] Vitamin E may be incorporated into the composition in the form of alpha-tocopherol, alpha-tocopherol acetate, alpha-tocopherol succinate, alpha-tocopherol nicotinate, alpha-tocopherol.

[0040] Vitamin C may be incorporated into the composition in the form of ascorbic acid.

[0041] Vitamin B3 may be incorporated into the compositions of the present invention as such or in the form of niacin, nicotinic acid, nicotinamide, niacinamide, nicotinamide adenine dinucleotide, NAD, nicotinic acid mononucleotide, NicMN, pyridine-3-carboxylic acid.

[0042] Vitamin B5 may be incorporated into the compositions of the present invention as such or in the form of pantothenic acid-pantothenate, panthenol.

[0043] Vitamin B6 may be incorporated into the compositions of the present invention as such or in the form of pyridoxine, pyridoxal, pyridoxamine, or pyridoxine hydrochloride.

[0044] Vitamin B1 may be incorporated into the compositions of the present invention as such or in the form of thiamine, thiamine pyrophosphate, TPP, thiamine triphosphate, TTP, thiamine hydrochloride, thiamine mononitrate.

[0045] Vitamin B2 may be incorporated into the compositions of the present invention as such or in the form of riboflavin, flavin mononucleotide, FMN, flavin adenine dinucleotide, FAD, lactoflavin, or ovoflavin.

[0046] Vitamin B12 may be incorporated into the compositions of the present invention as it is, in the form of a physiologically acceptable salt or a mixture thereof, or via any source containing vitamin B12. In particular, vitamin B12 may be incorporated into the compositions in the pure form of vitamin B12, as cyanocobalamin, hydroxocobalamin, and any combination thereof.

[0047] In one embodiment, the present invention provides a method for producing a pharmaceutical composition comprising: a daily dose of fish oil in the range of about 100 to about 5000 mg per kg of the subject's body weight; a daily dose of L-arginine in the range of about 100 to about 50,000 mg per kg of the subject's body weight; a daily dose of vitamin E in the range of about 1 to about 80,000 mg / kg of body weight of the subject; a daily dose of vitamin C in the range of about 0.1 to about 2000 mg per kg of the subject's body weight; a daily dose of vitamin B3 in the range of about 0.2 to about 10 mg per kg of the subject's body weight; a daily dose of vitamin B5 in the range of about 0.08 to about 500 mg per kg of the subject's body weight; a daily dose of vitamin B6 in the range of about 0.03 to about 50 mg per kg of the subject's body weight; a daily dose of vitamin B1 in the range of about 0.03 to about 5 mg per kg of the subject's body weight; a daily dose of vitamin B2 in the range of about 0.03 to about 5 mg per kg of the subject's body weight; a daily dose of folic acid in the range of about 0.01 to about 5 mg per kg of the subject's body weight; a daily dose of biotin in the range of about 0.01 to about 0.1 mg per kg of subject body weight; and vitamin B12 in a daily dose ranging from about 0.001 to about 5 mg per kg of subject body weight.

[0048] In one embodiment, the present invention provides a method for producing a pharmaceutical composition comprising: a daily dose in the range of about 100 to about 5000 mg / kg of subject body weight, preferably in an amount in the range of about 200 to about 3000 mg / kg of subject body weight; L-arginine in a daily amount ranging from about 1,000 to about 50,000 mg per kg of subject body weight, preferably in an amount ranging from about 3,000 to about 30,000 mg per kg of subject body weight; Vitamin E in a daily amount ranging from about 100 to about 80,000 mg / kg of subject body weight, preferably in an amount ranging from about 500 to about 50,000 mg / kg of subject body weight; Vitamin C in a daily amount ranging from about 100 to about 2000 mg / kg of subject body weight, preferably in an amount ranging from about 500 to about 1000 mg / kg of subject body weight; Vitamin B3 in a daily dose ranging from about 1 to about 10 mg per kg of subject body weight, preferably in an amount ranging from about 2 to about 6 mg per kg of subject body weight; Vitamin B5 in a daily amount ranging from about 50 to about 500 mg per kg of subject body weight, preferably in an amount ranging from about 100 to about 200 mg per kg of subject body weight; Vitamin B6 in a daily dose ranging from about 0.5 to about 50 mg per kg of subject body weight, preferably in an amount ranging from about 1 to about 25 mg per kg of subject body weight; Vitamin B1 in a daily dose ranging from about 0.2 to about 5 mg per kg of subject body weight, preferably in an amount ranging from about 0.5 to about 2 mg per kg of subject body weight; Vitamin B2 in a daily amount ranging from about 0.2 to about 5 mg per kg of subject body weight, preferably in an amount ranging from about 0.5 to about 2 mg per kg of subject body weight; folic acid in a daily amount ranging from about 0.2 to about 5 mg / kg of subject body weight, preferably in an amount ranging from about 0.5 to about 1 mg / kg of subject body weight; biotin in a daily amount ranging from about 0.01 to about 0.1 mg / kg of subject body weight, preferably in an amount ranging from about 0.02 to about 0.04 mg / kg of subject body weight; and vitamin B12 in an amount ranging from about 0.5 to about 5 mg per kg of subject body weight per day, preferably in an amount ranging from about 1.5 to about 2 mg per kg of subject body weight per day.

[0049] In a preferred embodiment, the nutritional composition administered to the pet animal comprises: a daily amount of fish oil in the range of about 100 to about 5000 mg per kg of pet animal body weight, preferably in an amount in the range of about 200 to about 3000 mg per kg of pet animal body weight; L-arginine in a daily amount ranging from about 100 to about 600 mg per kg of pet animal body weight, preferably 375 mg / kg BW for dogs and 575 mg / kg BW for cats; a daily dose of vitamin E in the range of about 1 to about 100 mg per kg of body weight of the pet animal, preferably 8 mg / kg BW for dogs and 14 mg / kg BW for cats, 8.27 mg / kg BW; a daily dose of vitamin C in the range of about 0.1 to about 10 mg per kg of body weight of the pet animal, preferably 1.3 mg / kg BW for dogs and 2 mg / kg BW for cats; a daily dose of vitamin B3 in the range of about 0.2 to about 10 mg / kg body weight of the pet animal, preferably 1.5 mg / kg BW for dogs; Vitamin B5 in a daily amount ranging from about 0.08 to about 20 mg per kg of body weight of the pet animal, preferably 0.5 mg / kg BW for dogs and 1.4 mg / kg BW for cats; Vitamin B6 in a daily amount ranging from about 0.0.3 to about 10 mg per kg of body weight of the pet animal, preferably 0.2 mg / kg BW for dogs and 0.5 mg / kg BW for cats; Vitamin B1 in a daily amount ranging from about 0.03 to about 5 mg per kg of body weight of the pet animal, preferably 0.3 mg / kg BW for dogs and 1.4 mg / kg BW for cats; a daily dose of vitamin B2 in the range of about 0.03 to about 5 mg per kg of body weight of the pet animal, preferably 0.2 mg / kg BW for dogs and 0.8 mg / kg BW for cats; a daily amount of folic acid in the range of about 0.01 to about 5 mg per kg of body weight of the pet animal, preferably 0.06 mg / kg BW for dogs and 0.11 mg / kg BW for cats; a daily dose of biotin in the range of about 0.01 to about 0.1 mg per kg of pet animal body weight; and a daily dose of vitamin B12 in the range of about 0.001 to about 5 mg per kg of pet animal body weight, preferably 0.015 mg / kg BW for dogs and 0.002 mg / kg BW for cats.

[0050] In one embodiment, the present invention relates to the nutritional composition as described above, wherein the subject is an individual at risk of or suffering from renal failure, renal dysfunction, or / and renal disease.

[0051] In one embodiment, the present invention relates to the nutritional composition as described above, wherein the individual is a human, a livestock, or a pet.

[0052] In one embodiment, the present invention relates to the aforementioned nutritional composition, wherein the muscle wasting is associated with renal failure, renal dysfunction, or / and renal disease.

[0053] In one embodiment, the present invention relates to the nutritional composition as described above, wherein the renal failure, renal impairment or / and renal disease is selected from the list of chronic kidney disease, PEW, end stage renal disease, renal failure due to intensive care unit admission, acute kidney injury.

[0054] In one embodiment, the present invention relates to the nutritional composition as described above, wherein the disease or condition associated with muscle loss is selected from the list consisting of muscle wasting, muscle loss due to kidney failure or impaired kidney function, muscle loss associated with chronic kidney disease, muscle loss due to intensive care unit admission during kidney failure, metabolic acidosis in chronic kidney disease, PEW, or a combination thereof.

[0055] In one embodiment, the present invention relates to a nutritional composition as described above, comprising at least three ingredients selected from the group above.

[0056] In one embodiment, the present invention relates to a nutritional composition as described above, comprising at least four ingredients selected from the group above.

[0057] In one embodiment, the present invention relates to a nutritional composition as described above, comprising at least five ingredients selected from the group above.

[0058] In one embodiment, the present invention relates to a nutritional composition as described above, comprising at least six ingredients selected from the group above.

[0059] In one embodiment, the present invention relates to a nutritional composition as described above, comprising at least seven ingredients selected from the group above.

[0060] In one embodiment, the present invention relates to a nutritional composition as described above, comprising at least eight ingredients selected from the group above.

[0061] In one embodiment, the present invention relates to a nutritional composition as described above, comprising at least nine ingredients selected from the group above.

[0062] In one embodiment, the present invention relates to a nutritional composition as described above, comprising at least 10 ingredients selected from the group above.

[0063] In one embodiment, the present invention relates to a nutritional composition as described above, comprising at least 11 ingredients selected from the group above.

[0064] In one embodiment, the present invention relates to a nutritional composition as described above, comprising at least 12 ingredients selected from the group above.

[0065] In one embodiment, the present invention relates to the nutritional composition described above for use in improving the levels of at least one amino acid.

[0066] In one embodiment, the present invention relates to the aforementioned nutritional composition, wherein the at least one amino acid is selected from the group consisting of leucine, lysine, arginine, methionine, and glutamine.

[0067] The nutritional compositions disclosed herein can use any of a variety of formulations for administration.

[0068] In a preferred embodiment, the formulation for administration is oral in the various types of pharmaceutical preparations, foods, and food products described above.

[0069] The compositions of the present disclosure may include any additional or optional ingredients, components, or restrictions described herein or otherwise useful in dietary therapy.

[0070] Those skilled in the art will identify appropriate amounts of the above nutrients, metabolic precursors, or metabolites of metabolic precursors to achieve the maximum tolerable levels of the above nutrients, metabolic precursors, or metabolites of metabolic precursors in the nutritional composition after administration.

[0071] In one embodiment, the present invention relates to a method for preventing and / or treating a disease or condition associated with muscle wasting, comprising the step of administering to a subject in need thereof an effective amount of the nutritional composition described above.

[0072] In one embodiment, the present invention relates to the aforementioned method, wherein the subject is an individual at risk of or suffering from renal failure, renal impairment, or / and renal disease.

[0073] In one embodiment, the present invention relates to the aforementioned method, wherein the muscle wasting is associated with renal failure, renal dysfunction, or / and renal disease.

[0074] In one embodiment, the present invention relates to the above-mentioned method, wherein the renal failure, renal dysfunction or / and renal disease is selected from the list of chronic kidney disease, PEW, end stage renal disease, renal failure due to admission in intensive care unit, acute kidney injury.

[0075] In one embodiment, the present invention relates to the aforementioned method, wherein the disease or condition associated with muscle loss is selected from the list consisting of muscle wasting, muscle loss due to kidney failure or impaired kidney function, muscle loss associated with chronic kidney disease, muscle loss due to admission to an intensive care unit during kidney failure, metabolic acidosis during chronic kidney disease, PEW, or a combination thereof.

[0076] In one embodiment, the present invention relates to the aforementioned method, wherein the level of at least one amino acid is improved.

[0077] In one embodiment, the present invention relates to the aforementioned method, wherein the at least one amino acid is selected from the group consisting of leucine, lysine, arginine, methionine, and glutamine.

[0078] Health benefits The health benefits of the present invention can be preventative, e.g., preventing impaired protein biosynthesis and the resulting muscle wasting state, or curative, e.g., treating a disease or condition associated with muscle wasting, such as muscle wasting due to kidney failure or impaired kidney function, muscle wasting associated with chronic kidney disease, muscle wasting due to intensive care unit admission during kidney failure, metabolic acidosis during chronic kidney disease, PEW, or a combination thereof, in a subject at risk for or suffering from kidney disease.

[0079] The composition of the present invention contains specific ingredients that improve the levels of amino acids, which are important nutrients for muscle repair and growth in the human body, transport energy to muscles in the human body, and at the same time, affect the inhibition of muscle protein loss.

[0080] These beneficial effects are particularly important in subjects with renal failure and / or kidney disease, such as chronic kidney disease, PEW, end-stage renal disease, kidney failure due to hospitalization in an intensive care unit, acute kidney injury, etc. Renal failure and / or kidney disease experience a large and constant loss of AA that can be manifested in the urine, which leads to impaired muscle protein synthesis and consequent muscle deterioration, such as loss of muscle mass and muscle wasting.

[0081] Other advantages of the present invention are improving muscle endurance and / or efficiency, muscle fiber size, and reducing muscle atrophy.

[0082] Thus, the benefits of the present invention are the maintenance of protein biosynthesis, prevention of muscle loss and muscle wasting, maintenance of healthy muscle mass, and treatment of muscle loss and disease in subjects with kidney disease.

[0083] Example The following non-limiting examples generally illustrate the concepts underlying the embodiments disclosed herein.

[0084] Figure 1a shows the urinary leucine levels measured in mice after 8 weeks of treatment with Renal Protective Blend (RPB) compared with the vehicle (diabetic, db / db+V) and control (healthy, db / m+V) groups after 8 weeks of treatment with 100 μL of 0.5% carboxymethylcellulose. Urinary leucine levels were measured using liquid-liquid extraction with 13C-yeast as an internal standard. 20 μL of urine was directly extracted into 1300 μL of cold methanol:water:chloroform (5:3:5 (v / v)). All samples were agitated in a shaker (Thermomixer C, Eppendorf) at 1500 rpm and 4°C for 10 minutes, followed by centrifugation at 15,000 rpm and 4°C for 10 minutes. After the centrifugation step, two phases were obtained: an upper phase containing polar metabolites and a lower phase containing nonpolar metabolites. Furthermore, a protein layer remained in the middle between the two phases. The upper phase was dried overnight in a vacuum centrifuge at 4 °C and 5 mbar and dissolved in 60 μL of 60% (v / v) acetonitrile:water prior to analysis. The protein layer was quantified by bicinchoninic acid (BCA) assay (ThermoFisher Scientific) and used for subsequent metabolite concentration normalization. 2 μL of each sample was injected onto a hydrophilic interaction chromatography (HILIC) analytical column. Separation was achieved by applying a linear solvent gradient. The mobile phase, solvent A, was 10 mM ammonium acetate (NH4Ac) and 0.04% (v / v) ammonium hydroxide (NH4OH) in H2O (pH ∼9.3), and solvent B was acetonitrile (ACN). The eluting metabolite leucine was analyzed using an Orbitrap mass spectrometer (Orbitrap Fusion Lumos Tribrid, Thermo Scientific) equipped with a heated electrospray ionization (H-ESI) source. Ionization was performed using negative ion mode (3 kV) and positive ion mode (3.5 kV) with on-the-fly alternating switching. Xcalibur v4.1.31.9 (Thermo Scientific) software was used for instrument control, data acquisition, and processing.

[0085] Data showed that urinary leucine levels were significantly reduced in RPB-treated mice compared with diabetic controls, which was interpreted as better renal reabsorption through proximal tubule cells preserving circulating amounts of leucine for its beneficial effects on muscle.

[0086] Figure 1b shows plasma leucine levels measured in mice after 8 weeks of treatment with the renal protective blend (RPB) compared with the vehicle (diabetic, db / db+V) and control (healthy, db / m+V) groups after 8 weeks of treatment with 100 μL of 0.5% carboxymethylcellulose. Plasma leucine levels were measured using liquid-liquid extraction with 13C-yeast as an internal standard. 20 μL of urine was directly extracted with 1300 μL of cold methanol:water:chloroform (5:3:5 (v / v)). All samples were agitated in a shaker (Thermomixer C, Eppendorf) at 1500 rpm and 4°C for 10 minutes, followed by centrifugation at 15,000 rpm and 4°C for 10 minutes. After the centrifugation step, two phases were obtained: an upper phase containing polar metabolites and a lower phase containing nonpolar metabolites. Furthermore, a protein layer remained in the middle between the two phases. The upper phase was dried overnight in a vacuum centrifuge at 4 °C and 5 mbar and dissolved in 60 μL of 60% (v / v) acetonitrile:water prior to analysis. The protein layer was quantified by bicinchoninic acid (BCA) assay (ThermoFisher Scientific) and used for subsequent metabolite concentration normalization. 2 μL of each sample was injected onto a hydrophilic interaction chromatography (HILIC) analytical column. Separation was achieved by applying a linear solvent gradient. The mobile phase, solvent A, was 10 mM ammonium acetate (NH4Ac) and 0.04% (v / v) ammonium hydroxide (NH4OH) in H2O (pH ∼9.3), and solvent B was acetonitrile (ACN). The eluting metabolite leucine was analyzed using an Orbitrap mass spectrometer (Orbitrap Fusion Lumos Tribrid, Thermo Scientific) equipped with a heated electrospray ionization (H-ESI) source. Ionization was performed using negative ion mode (3 kV) and positive ion mode (3.5 kV) with on-the-fly alternating switching. Xcalibur v4.1.31.9 (Thermo Scientific) software was used for instrument control, data acquisition, and processing.

[0087] The data did not show any differences between RPB-treated mice and diabetic controls.

[0088] Figure 2a shows the urinary lysine levels measured in mice after 8 weeks of treatment with the renal protective blend (RPB) compared with the vehicle group (diabetic, db / db+V group) and the control group (healthy, db / m+V group) after 8 weeks of treatment with 100 μL of 0.5% carboxymethylcellulose. Urinary lysine levels were measured using liquid-liquid extraction using 13C-yeast as an internal standard. 20 μL of urine was directly extracted into 1300 μL of cold methanol:water:chloroform (5:3:5 (v / v)). All samples were agitated in a shaker (Thermomixer C, Eppendorf) at 1500 rpm and 4°C for 10 minutes, followed by centrifugation at 15,000 rpm and 4°C for 10 minutes. After the centrifugation step, two phases were obtained: an upper phase containing polar metabolites and a lower phase containing nonpolar metabolites. Furthermore, a protein layer remained in the middle between the two phases. The upper phase was dried overnight in a vacuum centrifuge at 4 °C and 5 mbar and dissolved in 60 μL of 60% (v / v) acetonitrile:water prior to analysis. The protein layer was quantified by bicinchoninic acid (BCA) assay (ThermoFisher Scientific) and used for subsequent metabolite concentration normalization. 2 μL of each sample was injected onto a hydrophilic interaction chromatography (HILIC) analytical column. Separation was achieved by applying a linear solvent gradient. The mobile phase, solvent A, was 10 mM ammonium acetate (NH4Ac) and 0.04% (v / v) ammonium hydroxide (NH4OH) in H2O (pH ∼9.3), and solvent B was acetonitrile (ACN). The eluting metabolite lysine was analyzed using an Orbitrap mass spectrometer (Orbitrap Fusion Lumos Tribrid, Thermo Scientific) equipped with a heated electrospray ionization (H-ESI) source. Ionization was performed using negative ion mode (3 kV) and positive ion mode (3.5 kV) with on-the-fly alternating switching. Xcalibur v4.1.31.9 (Thermo Scientific) software was used for instrument control, data acquisition, and processing.

[0089] Data showed that urinary lysine levels were significantly reduced in RPB-treated mice compared with diabetic controls, which was interpreted as better renal reabsorption through proximal tubule cells, preserving circulating lysine for its beneficial effects on muscle.

[0090] Figure 2b shows plasma lysine levels measured in mice after 8 weeks of treatment with the renal protective blend (RPB) compared with the vehicle (diabetic, db / db+V) and control (healthy, db / m+V) groups after 8 weeks of treatment with 100 μL of 0.5% carboxymethylcellulose. Plasma lysine levels were measured using liquid-liquid extraction using 13C-yeast as an internal standard. 20 μL of urine was directly extracted with 1300 μL of cold methanol:water:chloroform (5:3:5 (v / v)). All samples were agitated in a shaker (Thermomixer C, Eppendorf) at 1500 rpm and 4°C for 10 minutes, followed by centrifugation at 15,000 rpm and 4°C for 10 minutes. After the centrifugation step, two phases were obtained: an upper phase containing polar metabolites and a lower phase containing nonpolar metabolites. Furthermore, a protein layer remained in the middle between the two phases. The upper phase was dried overnight in a vacuum centrifuge at 4 °C and 5 mbar and dissolved in 60 μL of 60% (v / v) acetonitrile:water prior to analysis. The protein layer was quantified by bicinchoninic acid (BCA) assay (ThermoFisher Scientific) and used for subsequent metabolite concentration normalization. 2 μL of each sample was injected onto a hydrophilic interaction chromatography (HILIC) analytical column. Separation was achieved by applying a linear solvent gradient. The mobile phase, solvent A, was 10 mM ammonium acetate (NH4Ac) and 0.04% (v / v) ammonium hydroxide (NH4OH) in H2O (pH ∼9.3), and solvent B was acetonitrile (ACN). The eluting metabolite lysine was analyzed using an Orbitrap mass spectrometer (Orbitrap Fusion Lumos Tribrid, Thermo Scientific) equipped with a heated electrospray ionization (H-ESI) source. Ionization was performed using negative ion mode (3 kV) and positive ion mode (3.5 kV) with on-the-fly alternating switching. Xcalibur v4.1.31.9 (Thermo Scientific) software was used for instrument control, data acquisition, and processing.

[0091] The data did not show any differences between RPB-treated mice and diabetic controls.

[0092] Figure 3a shows urinary arginine levels measured in mice after 8 weeks of treatment with the renal protective blend (RPB) compared with the vehicle group (diabetic, db / db+V group) and the control group (healthy, db / m+V group) after 8 weeks of treatment with 100 μL of 0.5% carboxymethylcellulose. Urinary arginine levels were measured using liquid-liquid extraction using 13C-yeast as an internal standard. 20 μL of urine was directly extracted into 1300 μL of cold methanol:water:chloroform (5:3:5 (v / v)). All samples were agitated in a shaker (Thermomixer C, Eppendorf) at 1500 rpm and 4°C for 10 minutes, followed by centrifugation at 15,000 rpm and 4°C for 10 minutes. After the centrifugation step, two phases were obtained: an upper phase containing polar metabolites and a lower phase containing nonpolar metabolites. Furthermore, a protein layer remained in the middle between the two phases. The upper phase was dried overnight in a vacuum centrifuge at 4 °C and 5 mbar and dissolved in 60 μL of 60% (v / v) acetonitrile:water prior to analysis. The protein layer was quantified by bicinchoninic acid (BCA) assay (ThermoFisher Scientific) and used for subsequent metabolite concentration normalization. 2 μL of each sample was injected onto a hydrophilic interaction chromatography (HILIC) analytical column. Separation was achieved by applying a linear solvent gradient. The mobile phase, solvent A, was 10 mM ammonium acetate (NH4Ac) and 0.04% (v / v) ammonium hydroxide (NH4OH) in H2O (pH ∼9.3), and solvent B was acetonitrile (ACN). The eluting metabolite arginine was analyzed using an Orbitrap mass spectrometer (Orbitrap Fusion Lumos Tribrid, Thermo Scientific) equipped with a heated electrospray ionization (H-ESI) source. Ionization was performed using negative ion mode (3 kV) and positive ion mode (3.5 kV) with on-the-fly alternating switching. Xcalibur v4.1.31.9 (Thermo Scientific) software was used for instrument control, data acquisition, and processing.

[0093] The data showed that mice treated with RPB had significantly increased urinary arginine levels compared to diabetic controls, due to the arginine supplementation present in the blend.

[0094] Figure 3b shows plasma arginine levels measured in mice after 8 weeks of treatment with the renal protective blend (RPB) compared with the vehicle (diabetic, db / db+V) and control (healthy, db / m+V) groups after 8 weeks of treatment with 100 μL of 0.5% carboxymethylcellulose. Plasma arginine levels were measured using liquid-liquid extraction with 13C-yeast as an internal standard. 20 μL of urine was directly extracted with 1300 μL of cold methanol:water:chloroform (5:3:5 (v / v)). All samples were agitated in a shaker (Thermomixer C, Eppendorf) at 1500 rpm and 4°C for 10 minutes, followed by centrifugation at 15,000 rpm and 4°C for 10 minutes. After the centrifugation step, two phases were obtained: an upper phase containing polar metabolites and a lower phase containing nonpolar metabolites. Furthermore, a protein layer remained in the middle between the two phases. The upper phase was dried overnight in a vacuum centrifuge at 4 °C and 5 mbar and dissolved in 60 μL of 60% (v / v) acetonitrile:water prior to analysis. The protein layer was quantified by bicinchoninic acid (BCA) assay (ThermoFisher Scientific) and used for subsequent metabolite concentration normalization. 2 μL of each sample was injected onto a hydrophilic interaction chromatography (HILIC) analytical column. Separation was achieved by applying a linear solvent gradient. The mobile phase, solvent A, was 10 mM ammonium acetate (NH4Ac) and 0.04% (v / v) ammonium hydroxide (NH4OH) in H2O (pH ∼9.3), and solvent B was acetonitrile (ACN). The eluting metabolite arginine was analyzed using an Orbitrap mass spectrometer (Orbitrap Fusion Lumos Tribrid, Thermo Scientific) equipped with a heated electrospray ionization (H-ESI) source. Ionization was performed using negative ion mode (3 kV) and positive ion mode (3.5 kV) with on-the-fly alternating switching. Xcalibur v4.1.31.9 (Thermo Scientific) software was used for instrument control, data acquisition, and processing.

[0095] The data showed that plasma arginine was significantly increased in mice treated with RPB compared with diabetic controls. RPB supplementation rescued the arginine depletion present in the diabetic state.

[0096] Figure 4a shows the urinary methionine levels measured in mice after 8 weeks of treatment with the renal protective blend (RPB) compared with the vehicle group (diabetic, db / db+V group) and the control group (healthy, db / m+V group) after 8 weeks of treatment with 100 μL of 0.5% carboxymethylcellulose. Urinary methionine levels were measured using liquid-liquid extraction using 13C-yeast as an internal standard. 20 μL of urine was directly extracted into 1300 μL of cold methanol:water:chloroform (5:3:5 (v / v)). All samples were agitated in a shaker (Thermomixer C, Eppendorf) at 1500 rpm and 4°C for 10 minutes, followed by centrifugation at 15,000 rpm and 4°C for 10 minutes. After the centrifugation step, two phases were obtained: an upper phase containing polar metabolites and a lower phase containing nonpolar metabolites. Furthermore, a protein layer remained in the middle between the two phases. The upper phase was dried overnight in a vacuum centrifuge at 4 °C and 5 mbar and dissolved in 60 μL of 60% (v / v) acetonitrile:water prior to analysis. The protein layer was quantified by bicinchoninic acid (BCA) assay (ThermoFisher Scientific) and used for subsequent metabolite concentration normalization. 2 μL of each sample was injected onto a hydrophilic interaction chromatography (HILIC) analytical column. Separation was achieved by applying a linear solvent gradient. The mobile phase, solvent A, was 10 mM ammonium acetate (NH4Ac) and 0.04% (v / v) ammonium hydroxide (NH4OH) in H2O (pH ∼9.3), and solvent B was acetonitrile (ACN). The eluting metabolite methionine was analyzed using an Orbitrap mass spectrometer (Orbitrap Fusion Lumos Tribrid, Thermo Scientific) equipped with a heated electrospray ionization (H-ESI) source. Ionization was performed using negative ion mode (3 kV) and positive ion mode (3.5 kV) with on-the-fly alternating switching. Xcalibur v4.1.31.9 (Thermo Scientific) software was used for instrument control, data acquisition, and processing.

[0097] The data showed that RPB-treated mice had significantly reduced urinary methionine levels compared to diabetic controls, returning to levels in healthy controls, and that reductions in body or dietary methionine are associated with health benefits.

[0098] Figure 4b shows plasma methionine levels measured in mice after 8 weeks of treatment with the renal protective blend (RPB) compared with the vehicle group (diabetic, db / db+V group) and the control group (healthy, db / m+V group) after 8 weeks of treatment with 100 μL of 0.5% carboxymethylcellulose. Plasma methionine levels were measured using liquid-liquid extraction using 13C-yeast as an internal standard. 20 μL of urine was directly extracted with 1300 μL of cold methanol:water:chloroform (5:3:5 (v / v)). All samples were agitated in a shaker (Thermomixer C, Eppendorf) at 1500 rpm and 4°C for 10 minutes, followed by centrifugation at 15,000 rpm and 4°C for 10 minutes. After the centrifugation step, two phases were obtained: an upper phase containing polar metabolites and a lower phase containing nonpolar metabolites. Furthermore, a protein layer remained in the middle between the two phases. The upper phase was dried overnight in a vacuum centrifuge at 4 °C and 5 mbar and dissolved in 60 μL of 60% (v / v) acetonitrile:water prior to analysis. The protein layer was quantified by bicinchoninic acid (BCA) assay (ThermoFisher Scientific) and used for subsequent metabolite concentration normalization. 2 μL of each sample was injected onto a hydrophilic interaction chromatography (HILIC) analytical column. Separation was achieved by applying a linear solvent gradient. The mobile phase, solvent A, was 10 mM ammonium acetate (NH4Ac) and 0.04% (v / v) ammonium hydroxide (NH4OH) in H2O (pH ∼9.3), and solvent B was acetonitrile (ACN). The eluting metabolite methionine was analyzed using an Orbitrap mass spectrometer (Orbitrap Fusion Lumos Tribrid, Thermo Scientific) equipped with a heated electrospray ionization (H-ESI) source. Ionization was performed using negative ion mode (3 kV) and positive ion mode (3.5 kV) with on-the-fly alternating switching. Xcalibur v4.1.31.9 (Thermo Scientific) software was used for instrument control, data acquisition, and processing.

[0099] The data show a strong trend towards a decrease in plasma methionine levels in RPB-treated mice compared to diabetic controls, consistent with the fact that a reduction in body or dietary methionine is associated with health benefits.

[0100] Figure 5 shows urinary glutamine levels measured in mice after 8 weeks of treatment with the renal protective blend (RPB) compared with the vehicle group (diabetic, db / db+V group) and the control group (healthy, db / m+V group) after 8 weeks of treatment with 100 μL of 0.5% carboxymethylcellulose. Urinary glutamine levels were measured using liquid-liquid extraction using 13C-yeast as an internal standard. 20 μL of urine was directly extracted into 1300 μL of cold methanol:water:chloroform (5:3:5 (v / v)). All samples were agitated in a shaker (Thermomixer C, Eppendorf) at 1500 rpm and 4°C for 10 minutes, followed by centrifugation at 15,000 rpm and 4°C for 10 minutes. After the centrifugation step, two phases were obtained: an upper phase containing polar metabolites and a lower phase containing nonpolar metabolites. Furthermore, a protein layer remained in the middle between the two phases. The upper phase was dried overnight in a vacuum centrifuge at 4 °C and 5 mbar and dissolved in 60 μL of 60% (v / v) acetonitrile:water prior to analysis. The protein layer was quantified by bicinchoninic acid (BCA) assay (ThermoFisher Scientific) and used for subsequent metabolite concentration normalization. 2 μL of each sample was injected onto a hydrophilic interaction chromatography (HILIC) analytical column. Separation was achieved by applying a linear solvent gradient. The mobile phase, solvent A, was 10 mM ammonium acetate (NH4Ac) and 0.04% (v / v) ammonium hydroxide (NH4OH) in H2O (pH ∼9.3), and solvent B was acetonitrile (ACN). The eluting metabolite glutamine was analyzed using an Orbitrap mass spectrometer (Orbitrap Fusion Lumos Tribrid, Thermo Scientific) equipped with a heated electrospray ionization (H-ESI) source. Ionization was performed using negative ion mode (3 kV) and positive ion mode (3.5 kV) with on-the-fly alternating switching. Xcalibur v4.1.31.9 (Thermo Scientific) software was used for instrument control, data acquisition, and processing.

[0101] The data showed that mice treated with RPB had a trend towards a decrease in urinary glutamine levels compared to diabetic controls.

[0102] This preclinical study demonstrates that ingestion of the nutritional compositions disclosed herein prevents the loss of important amino acids in muscle protein and therefore prevents and / or treats diseases or conditions associated with muscle wasting, particularly in subjects at risk for or suffering from renal failure, renal impairment, or / and renal disease, such as CKD, PEW, ESRD, renal failure due to ICU admission, AKI, etc.

[0103] It should be understood that various changes and modifications to the preferred embodiments described herein will be apparent to those skilled in the art. Such changes and modifications can be made without departing from the spirit and scope of the present subject matter and without diminishing its intended advantages. Accordingly, such changes and modifications are intended to be covered by the appended claims.

Claims

1. 1. A nutritional composition for use in the prevention and / or treatment of a disease or condition associated with muscle wasting in a subject in need thereof, comprising: fish oil, L-arginine, Vitamin E, Vitamin C, Vitamin B3, Vitamin B5, Vitamin B6, Vitamin B1, Vitamin B2, folic acid, biotin, A nutritional composition comprising at least two ingredients selected from the group consisting of: vitamin B12.

2. The nutritional composition a daily amount of fish oil in the range of about 100 to about 5000 mg / kg body weight of said subject; a daily dose of L-arginine in the range of about 100 to about 50,000 mg / kg body weight of the subject; a daily amount of vitamin E in the range of about 1 to about 80,000 mg / kg body weight of said subject; a daily amount of vitamin C in the range of about 0.1 to about 2000 mg / kg body weight of said subject; a daily amount of vitamin B3 in the range of about 0.2 to about 10 mg / kg body weight of said subject; a daily dose of vitamin B5 in the range of about 0.08 to about 500 mg / kg body weight of said subject; a daily amount of vitamin B6 in the range of about 0.0.3 to about 50 mg / kg body weight of said subject; a daily amount of vitamin B1 in the range of about 0.03 to about 5 mg / kg body weight of said subject; a daily amount of vitamin B2 in the range of about 0.03 to about 5 mg / kg body weight of said subject; a daily amount of folic acid in the range of about 0.01 to about 5 mg / kg body weight of said subject; a daily dose of biotin in the range of about 0.01 to about 0.1 mg / kg body weight of said subject; 10. The nutritional composition of claim 1, comprising at least two ingredients selected from the group consisting of: vitamin B12 in a daily dose ranging from about 0.001 to about 5 mg per kg of body weight of the subject.

3. 3. The nutritional composition of claim 1 or 2, wherein the subject is an individual at risk of or suffering from renal failure, renal dysfunction, or / and renal disease.

4. The nutritional composition according to any one of claims 1 to 3, wherein the individual is a human, a livestock or a pet.

5. The nutritional composition according to any one of claims 1 to 4, wherein the muscle loss is associated with renal failure, renal dysfunction, or / and renal disease.

6. 6. The nutritional composition of any one of claims 1 to 5, wherein said renal failure, renal impairment or / and said renal disease is selected from the list of chronic kidney disease, PEW, end stage renal disease, renal failure due to intensive care unit admission, acute kidney injury.

7. 7. The nutritional composition of any one of claims 1 to 6, wherein said disease or condition associated with muscle loss is selected from the list consisting of muscle wasting, muscle loss due to kidney failure or impaired kidney function, muscle loss associated with chronic kidney disease, muscle loss due to admission to an intensive care unit during kidney failure, metabolic acidosis during chronic kidney disease, PEW, or a combination thereof.

8. 8. A nutritional composition according to any one of claims 1 to 7, comprising at least 3, or at least 4, or at least 5, or at least 6, or at least 7, or at least 8, or at least 9, or at least 10, or at least 11, or at least 12 components selected from the group.

9. A nutritional composition according to any one of claims 1 to 8 for use in improving the levels of at least one amino acid.

10. 11. The nutritional composition of claim 10, wherein the at least one amino acid is selected from the group consisting of leucine, lysine, arginine, methionine, and glutamine.

11. 11. A method for preventing and / or treating a disease or condition associated with muscle wasting, comprising administering to a subject in need of said prevention and / or said treatment an effective amount of the nutritional composition of any one of claims 1 to 10.

12. 12. The method of claim 11, wherein the subject is an individual at risk of or suffering from renal failure, renal impairment, or / and renal disease.

13. The method according to any one of claims 1 to 12, wherein the muscle wasting is associated with renal failure, renal dysfunction, or / and renal disease.

14. 14. The method of claim 11 or 13, wherein the renal failure, renal impairment, or / and renal disease is selected from the list of chronic kidney disease, PEW, end stage renal disease, renal failure due to admission to an intensive care unit, acute kidney injury.

15. 15. The method of any one of claims 11 to 14, wherein the disease or condition associated with muscle loss is selected from the list consisting of muscle wasting, muscle loss due to kidney failure or impaired kidney function, muscle loss associated with chronic kidney disease, muscle loss due to admission to an intensive care unit during kidney failure, metabolic acidosis during chronic kidney disease, PEW, or a combination thereof.

16. The method according to any one of claims 11 to 15, wherein the level of at least one amino acid is improved.

17. 17. The method of claim 16, wherein the at least one amino acid is selected from the group consisting of leucine, lysine, arginine, methionine, and glutamine.

Images