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

Abstract

The compositions comprise 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, vitamin B12, and are formulated for the prevention and / or treatment of a disease or condition associated with muscle decline in a subject in need thereof. Preferably, the subject in need is an individual at risk of or having renal failure, renal dysfunction or / and nephropathy, such as chronic nephropathy, protein energy consumption, end-stage nephropathy, renal failure due to hospitalization in an intensive care unit, acute kidney injury, and the muscle decline is selected from the group consisting of muscle depletion, muscle loss due to renal failure or dysfunction, muscle decline associated with chronic kidney disease, muscle loss due to hospitalization in intensive care units during renal failure, metabolic acidosis during chronic kidney disease, protein energy depletion, or a combination thereof. The method enables the prevention and / or treatment of at least one outcome of a disease or condition associated with muscle decline in a subject at risk of or having renal failure, renal dysfunction or / and kidney disease. The composition and the method can be used to improve the level of at least one amino acid.

Description

[0001] The present disclosure generally relates 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, renal dysfunction and / or renal disease, such as chronic kidney disease, protein energy wasting, end-stage renal disease, renal failure due to hospitalization in an intensive care unit, acute kidney injury. Background Art

[0002] Renal failure, dysfunction and / or diseases such as chronic kidney disease (CKD), protein energy wasting, end-stage renal disease (ESRD), renal failure due to hospitalization in the intensive care unit (ICU), acute kidney injury (AKI) may result in a sustained and excessive loss of some amino acids (AA).

[0003] Amino acids are the structural protein unit molecules of muscle, and their continued loss and / or insufficient amounts lead to high protein degradation and low protein synthesis, thus causing loss of muscle mass and muscle wasting.

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

[0005] While nutritional recommendations are often directed toward the overall improvement of muscle wasting, no data exist for the prevention and / or treatment of muscle wasting conditions or diseases associated with renal failure, dysfunction, or disease.

[0006] Therefore, there is a need to identify nutrients necessary for preventing and / or treating muscle wasting conditions or diseases associated with renal failure, dysfunction or disease.

[0007] Furthermore, 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 of or suffering from renal failure, renal dysfunction and / or renal disease, such as CKD, protein energy wasting, end-stage renal disease (ESRD), renal failure due to hospitalization in an ICU, acute kidney injury (AKI).

[0008] Purpose of the Invention

[0009] The object of the present invention is to provide a method and an optimal nutritional composition with specific ingredients for preventing and / or treating muscle wasting conditions or diseases associated with renal failure, dysfunction or disease, in particular such as CKD, protein energy wasting, ESRD, renal failure due to hospitalization in the ICU, AKI. Summary of the invention

[0010] Preclinical studies disclosed herein demonstrate that ingestion of a nutritional composition according to the present invention prevents the loss of key amino acids for muscle protein production, thereby preventing loss of muscle mass and muscle wasting in subjects with renal failure, dysfunction or disease.

[0011] Benefits of such improvements include preventing and / or treating muscle wasting conditions or diseases associated with kidney conditions or diseases.

[0012] Thus, the present disclosure as a whole relates to novel compositions and methods for preventing and / or treating diseases or conditions associated with muscle wasting, particularly in subjects with renal failure, renal dysfunction and / or renal disease, such as CKD, protein energy wasting, ESRD, renal failure due to hospitalization in an ICU, at risk for AKI, or suffering from the foregoing conditions.

[0013] Additional features and advantages are described herein, and will be apparent from the following figures and detailed description. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1a is a graph showing results from the Experimental Examples disclosed herein, which demonstrate that urinary leucine levels were reduced when the nutritional composition was administered.

[0015] Figure 1b is a graph showing results from the Experimental Examples disclosed herein, which demonstrate that plasma leucine levels did not change significantly when the nutritional composition was administered.

[0016] Figure 2a is a graph showing results from the Experimental Examples disclosed herein, which demonstrate that urinary lysine levels were reduced when the nutritional composition was administered.

[0017] Figure 2b is a graph showing results from the Experimental Examples disclosed herein, which demonstrate that plasma lysine levels did not change significantly when the nutritional composition was administered.

[0018] Figure 3a is a graph showing results from the Experimental Examples disclosed herein, which demonstrate that urinary arginine levels increased when the nutritional composition was administered.

[0019] Figure 3b is a graph showing results from the Experimental Examples disclosed herein, which demonstrate that plasma arginine levels increased when the nutritional composition was administered.

[0020] Figure 4a is a graph showing results from the Experimental Examples disclosed herein, which demonstrate that urinary methionine levels were reduced when the nutritional composition was administered.

[0021] Figure 4b is a graph showing results from the Experimental Examples disclosed herein, which demonstrate that plasma methionine levels were reduced when the nutritional composition was administered.

[0022] Figure 5 is a graph showing results from the Experimental Examples disclosed herein, which indicates a trend of decreased urinary glutamine levels when the nutritional composition is administered. DETAILED DESCRIPTION

[0023] definition

[0024] Some definitions are provided below. However, definitions may be located in the "Implementation" section below, and the above heading "Definitions" does not indicate that such disclosure in the "Implementation" section is not a definition.

[0025] In the context of the present invention, the expression "nutritional composition" refers to a composition for nourishing a subject. The nutritional composition is usually taken enterally, orally, parenterally or intravenously. Preferably, the nutritional composition is for oral use.

[0026] In addition, "nutritional composition" may refer to liquid, powder, gel, paste, solid, concentrate, suspension or ready-to-use enteral formula, oral formula, infant formula, children's formula, adult formula, porridge and / or cereal, food product, food composition, baby food, pet food. The composition of the present disclosure (including multiple embodiments described herein) may include, consist of or be substantially composed of the following elements: basic elements and restrictions described herein, and any other or optional ingredients, components or restrictions described herein or that can be used in diet. Food products according to the present invention include but are not limited to bread, cake, cookie, cracker, extruded snacks, potato products, rice products, corn products, wheat products, dairy products, yogurt, candy, hard candy, gummy candy, nutrition bar, breakfast cereal or beverage, including plant-based beverages such as fruit juice, milk shake, soy milk, rice milk or almond milk.

[0027] "Prevention" includes reducing the risk and / or severity of a disease or disorder. The terms "treatment" and "relief" include both preventive or prophylactic treatment (preventing and / or delaying the development of a target pathological condition or disorder), as well as curative, therapeutic or disease-modifying treatments, including curing, delaying, alleviating symptoms of a confirmed pathological condition or disorder and / or interrupting therapeutic measures for its progression; and treating patients at risk of contracting a disease or suspected of contracting a disease, as well as treating patients who are ill or have been diagnosed with a disease or medical condition. The term does not necessarily mean that the subject is treated until full recovery. The term "treatment" also refers to health maintenance and / or promotion in individuals who are not suffering from a disease but may be prone to developing unhealthy conditions. The terms "treatment" and "relief" are also intended to include strengthening or otherwise enhancing one or more major preventive or therapeutic measures. The terms "treatment" and "relief" are also intended to include dietary management of a disease or condition or dietary management for preventing or preventing a disease or condition. Treatment can be patient-related or doctor-related.

[0028] "Individual" is a mammal, preferably a human, livestock, or pet. In particular, the term "livestock" may include, but is not limited to, horses (e.g., pets or horses undergoing medical treatment), or cattle or poultry (e.g., cattle or poultry used in agriculture). In particular, the term "pet" means any animal that can benefit from or enjoy the compositions provided by the present disclosure. For example, the pet may be an avian, bovine, canine, equine, feline, caprine, wolf, murine, ovine, or porcine animal, but the pet may also be any suitable animal.

[0029] All percentages expressed herein are by weight of the total weight of the composition, unless otherwise indicated. As used herein, "about", "approximately" and "substantially" should be understood to refer to numbers within a certain numerical range, such as within the range of -10% to +10% of the mentioned number, preferably -5% to +5% of the mentioned number, more preferably -1% to +1% of the mentioned number, and most preferably -0.1% to +0.1% of the mentioned number. All numerical ranges herein should be understood to include all integers or fractions within the range. In addition, these numerical ranges should be understood to provide support for claims involving any number or subset of numbers within the range. For example, the disclosure of 1 to 10 should be understood to support ranges of 1 to 8, 3 to 7, 1 to 9, 3.6 to 4.6, 3.5 to 9.9, etc.

[0030] As used in this disclosure and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a component" or "the component" includes two or more components.

[0031] The words "include / comprise" will all be interpreted as inclusive and not exclusive. Similarly, the terms "include / comprise" and "or" should all be considered inclusive unless the context clearly prohibits such an interpretation. However, the compositions disclosed herein may not contain any elements not specifically disclosed herein. Therefore, disclosures of embodiments using the term "include / comprise" include disclosures of embodiments "consisting essentially of the specified components" and embodiments "consisting of the specified components." A composition or dosage unit "consisting essentially of" contains at least 50% by weight of the reference component, preferably at least 75% by weight of the reference component, more preferably at least 85% by weight of the reference component, and most preferably at least 95% by weight of the reference component.

[0032] 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 decline and / or renal dysfunction" should be interpreted as "muscle decline" or "renal dysfunction" or "both muscle decline and renal dysfunction".

[0033] As used herein, the terms "example" and "such as" (especially when followed by a list of terms) are exemplary and illustrative only and should not be considered exclusive or comprehensive. As used herein, one condition is "associated with" or "associated with" another condition means that the conditions occur at the same time, preferably means that the conditions are caused by the same underlying condition, and most preferably means that one of the identified conditions is caused by the other identified condition.

[0034] “Chronic kidney disease (CKD)” encompasses the presence of renal damage (i.e., proteinuria) or decreased renal function (i.e., 2 , GFR < 60 mL / min) for 3 months or longer, regardless of clinical diagnosis. CKD is divided into five stages based on GFR: 2 Greater than 90 mL / min (1st phase), every 1.73 m 2 60mL / min-89mL / min (2 phases), every 1.73m 2 30mL / min-59mL / min (3 phases), every 1.73m 2 15mL / min-29mL / min (4 phases) and every 1.73m 2 Less than 15 mL / min (stage 5). Early stage of chronic kidney disease includes stage 2 and stage 3 chronic kidney disease based on GFR: every 1.73 m 2 60mL / min-89mL / min (2 phases), every 1.73m 230mL / min-59mL / min (Stage 3). Preferably, "early stage of chronic kidney disease" covers stage 2 chronic kidney disease based on GFR: every 1.73m 2 60mL / min-89mL / min. Late stage of CKD includes stage 4 and 5 CKD based on GFR: every 1.73m 2 15mL / min-29mL / min (4 phases), and every 1.73m 2 Less than 15 mL / min (stage 5). Preferably, the advanced stage of chronic kidney disease encompasses stage 4 chronic kidney disease based on GFR: 2 15mL / min-29mL / min.

[0035] "End-stage renal disease (ESRD)" encompasses the condition of an individual with CKD who requires renal replacement therapy. Preferably, ESRD encompasses chronic kidney disease of stage 5 based on GFR: 2 Less than 15mL / min.

[0036] "Muscle wasting" encompasses a prolonged catabolic state in which muscle protein breakdown exceeds the rate of protein synthesis.

[0037] "Protein energy wasting" refers to the loss of body protein mass and fuel reserves in a subject due to a maladaptive metabolic state. Maladaptive metabolic states include nonspecific inflammatory processes, transient concurrent catabolic diseases; nutrient losses in the dialysate, acidemia, endocrine disorders such as resistance to insulin, growth hormone, and insulin-like growth factor-1, glucagonemia, hyperparathyroidism, and blood loss in the hemodialyzer, in the stool, or by blood draw.

[0038] As used herein, an "effective amount" is an amount that prevents a defect, treats a disease or medical condition in an individual, or more generally, reduces symptoms, manages the progression of its disease, or provides a nutritional, physiological or medical benefit to the individual. The relative terms "improve," "increase," "enhance," and the like refer to the effects of the compositions disclosed herein.

[0039] As used herein, "RPB" blends are defined in Table 1 below.

[0040] Table 1: RPB blends (mg / kg / day)

[0041] RPB fish oil 2000 L-Arginine 2000 Vitamin E acetate, 50% 100 Vitamin C 15 Niacin B3 4.5 Vitamin B5 3.5 Vitamin B6 2.4 Thiamine B1 1.5 Riboflavin B2 0.9 Folic acid 0.3 Biotin 0.08 Vitamin B12, 1% 2.25

[0042] Implementation

[0043] Amino acid (AA) residues form the second largest component, with only water being the largest component in human tissues, especially muscle.

[0044] In subjects with renal failure and / or renal diseases, such as chronic kidney disease, protein energy wasting, end-stage renal disease, renal failure due to hospitalization in an intensive care unit, acute kidney injury, high levels of specific AAs are shown in the urine, which means their significant and sustained loss in the human organism, resulting in their inability to be incorporated into muscles or failure of muscle protein synthesis, thus leading to muscle deterioration, such as loss of muscle mass and muscle wasting.

[0045] One of the most common diseases that causes muscle wasting is CKD. CKD is a gradual and progressive loss of the kidneys' ability to excrete waste, concentrate urine, reabsorb protein and AA, and conserve electrolytes. Unlike AKI, where kidney function is sudden but reversible, kidney function in CKD progresses toward ESRD and deteriorates irreversibly. CKD is caused by many different kinds of disease pathways that irreversibly change the function and structure of the kidneys over months or years.

[0046] Diabetes and hypertension are the main causes of CKD. Therefore, these studies are relevant to diabetic subjects.

[0047] The inventors have surprisingly identified specific nutrients that reduce urine levels of specific AAs, such as leucine, lysine, methionine and glutamine, and increase arginine. Considering that these AAs cannot be synthesized by the human body and can only be obtained under supplementation, it is crucial to maintain their levels in the blood and prevent the body from losing them due to renal dysfunction and / or disease. The reduction of said AAs in urine means preventing their loss in the subject's body and maintaining their levels sufficient for muscle protein production, thereby preventing and / or treating diseases or conditions associated with muscle deterioration.

[0048] Thus, in a first embodiment, the present invention relates to a nutritional composition for preventing and / or treating a disease or condition associated with muscle wasting in a subject in need thereof, the nutritional composition comprising at least two ingredients selected from the group consisting of:

[0049] fish oil,

[0050] L-Arginine,

[0051] Vitamin E,

[0052] Vitamin C,

[0053] Vitamin B3,

[0054] Vitamin B5,

[0055] Vitamin B6,

[0056] Vitamin B1,

[0057] Vitamin B2,

[0058] Folic acid,

[0059] Biotin,

[0060] Vitamin B12.

[0061] Fish oil generally contains 5% by weight or more, preferably 10% by weight or more, of DHA.

[0062] L-arginine may be naturally occurring or synthetic.

[0063] Vitamin E can be incorporated into the composition in the form of alpha-tocopherol, alpha-tocopherol acetate, alpha-tocopherol succinate, alpha-tocopherol nicotinate, a-tocopherol.

[0064] Vitamin C may be incorporated into the composition in the form of ascorbic acid.

[0065] Vitamin B3 may be incorporated into the composition of the present invention as such or in the form of niacin, nicotinic acid, niacinamide, niacinamide, niacinamide adenine dinucleotide, NAD, nicotinic acid mononucleotide, NicMN, pyridine-3-carboxylic acid.

[0066] Vitamin B5 may be incorporated into the composition of the present invention as such or in the form of pantothenic acid-pantothenate, panthenol.

[0067] Vitamin B6 may be incorporated into the composition of the present invention as such or in the form of pyridoxine, pyridoxal, pyridoxamine, or pyridoxine hydrochloride.

[0068] Vitamin B1 may be incorporated into the composition of the present invention as it is or in the form of thiamine, thiamine pyrophosphate, TPP, thiamine triphosphate, TTP, thiamine hydrochloride, thiamine mononitrate.

[0069] Vitamin B2 may be incorporated into the composition of the present invention as it is or in the form of riboflavin, flavin mononucleotide, FMN, flavin adenine dinucleotide, FAD, lactoflavin, or lutein.

[0070] Vitamin B12 can be incorporated into the composition of the present invention as such or in the form of its physiologically acceptable salt or mixture thereof, or through any source comprising vitamin B12. In particular, vitamin B12 can be incorporated into the composition in its pure form, such as cyanocobalamin, hydroxocobalamin and any combination thereof.

[0071] In one embodiment, the present invention relates to a nutritional composition as described above, comprising at least two ingredients selected from the group consisting of:

[0072] A daily amount ranges from about 100 mg to about 5000 mg of fish oil per kg of body weight of the subject,

[0073] The daily amount ranges from about 100 mg to about 50,000 mg of L-arginine per kg of body weight of the subject,

[0074] The daily amount ranges from about 1 mg to about 80,000 mg of vitamin E per kg of body weight of the subject,

[0075] The daily amount ranges from about 0.1 mg to about 2000 mg of vitamin C per kg of body weight of the subject,

[0076] The daily amount ranges from about 0.2 mg to about 10 mg of vitamin B3 per kg body weight of the subject,

[0077] The daily amount ranges from about 0.08 mg to about 500 mg of vitamin B5 per kg of body weight of the subject,

[0078] The daily amount ranges from about 0.03 mg to about 50 mg of vitamin B6 per kg of body weight of the subject,

[0079] The daily amount ranges from about 0.03 mg to about 5 mg of vitamin B1 per kg of body weight of the subject,

[0080] The daily amount ranges from about 0.03 mg to about 5 mg of vitamin B2 per kg of body weight of the subject,

[0081] The daily amount ranges from about 0.01 mg to about 5 mg of folic acid per kg body weight of the subject,

[0082] The daily amount ranges from about 0.01 mg to about 0.1 mg of biotin per kg of body weight of the subject,

[0083] The daily amount ranges from about 0.001 mg to about 5 mg of vitamin B12 per kg body weight of the subject.

[0084] In one embodiment, the invention relates to a nutritional composition as described above for administration to a human subject, said nutritional composition comprising at least two ingredients selected from the group consisting of:

[0085] a daily amount ranging from about 100 mg to about 5000 mg per kg of body weight of the subject, preferably an amount ranging from about 200 mg to about 3000 mg of fish oil per kg of body weight of the subject,

[0086] The daily amount ranges from about 1000 mg to about 50000 mg per kg of the subject's body weight, preferably from about 3000 mg to about 30000 mg of L-arginine per kg of the subject's body weight,

[0087] The daily amount ranges from about 100 mg to about 80,000 mg per kg of the subject's body weight, preferably from about 500 mg to about 50,000 mg of vitamin E per kg of the subject's body weight,

[0088] A daily amount ranging from about 100 mg to about 2000 mg, preferably an amount ranging from about 500 mg to about 1000 mg of vitamin C per kg of body weight of the subject,

[0089] A daily amount ranging from about 1 mg to about 10 mg per kg of body weight of the subject, preferably an amount ranging from about 2 mg to about 6 mg of vitamin B3 per kg of body weight of the subject,

[0090] A daily amount ranging from about 50 mg to about 500 mg per kg of body weight of the subject, preferably an amount ranging from about 100 mg to about 200 mg of vitamin B5 per kg of body weight of the subject,

[0091] The daily amount ranges from about 0.5 mg to about 50 mg per kg of the subject's body weight, preferably from about 1 mg to about 25 mg of vitamin B6 per kg of the subject's body weight,

[0092] The daily amount ranges from about 0.2 mg to about 5 mg per kg of the subject's body weight, preferably an amount ranges from about 0.5 mg to about 2 mg of vitamin B1 per kg of the subject's body weight,

[0093] The daily amount ranges from about 0.2 mg to about 5 mg per kg of the subject's body weight, preferably an amount ranges from about 0.5 mg to about 2 mg of vitamin B2 per kg of the subject's body weight,

[0094] A daily amount ranging from about 0.2 mg to about 5 mg, preferably an amount ranging from about 0.5 mg to about 1 mg, of folic acid per kg of body weight of the subject,

[0095] A daily amount ranging from about 0.01 mg to about 0.1 mg, preferably an amount ranging from about 0.02 mg to about 0.04 mg of biotin per kg of body weight of the subject,

[0096] The daily amount ranges from about 0.5 mg to about 5 mg, preferably an amount ranges from about 1.5 mg to about 2 mg of vitamin B12 per kg of body weight of the subject.

[0097] In a preferred embodiment, the nutritional composition administered to a pet animal comprises at least two ingredients selected from the group consisting of:

[0098] The daily amount ranges from about 100 mg to about 5000 mg per kg of the pet animal's body weight, preferably from about 200 mg to about 3000 mg of fish oil per kg of the pet animal's body weight,

[0099] The daily amount ranges from about 100 mg to about 600 mg, preferably 375 mg / kg BW for dogs and 575 mg / kg BW for cats, of L-arginine per kg body weight of the pet animal.

[0100] The daily amount ranges from about 1 mg 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 of vitamin E. 8.27 mg / kg BW.

[0101] The daily amount ranges from about 0.1 mg to about 10 mg, preferably 1.3 mg / kg BW for dogs and 2 mg / kg BW for cats, of vitamin C per kg body weight of the pet animal.

[0102] The daily amount ranges from about 0.2 mg to about 10 mg per kg body weight of the pet animal, preferably 1.5 mg / kg BW of vitamin B3 for dogs,

[0103] The daily amount ranges from about 0.08 mg to about 20 mg per kg body weight of the pet animal, preferably 0.5 mg / kg BW for dogs and 1.4 mg / kg BW for cats of vitamin B5,

[0104] The daily amount ranges from about 0.03 mg to about 10 mg per kg body weight of the pet animal, preferably 0.2 mg / kg BW for dogs and 0.5 mg / kg BW for cats of vitamin B6,

[0105] The daily amount ranges from about 0.03 mg to about 5 mg per kg body weight of the pet animal, preferably 0.3 mg / kg BW for dogs and 1.4 mg / kg BW for cats of vitamin B1,

[0106] The daily amount ranges from about 0.03 mg to about 5 mg per kg body weight of the pet animal, preferably 0.2 mg / kg BW for dogs and 0.8 mg / kg BW for cats of vitamin B2,

[0107] The daily amount ranges from about 0.01 mg to about 5 mg per kg body weight of the pet animal, preferably 0.06 mg / kg BW for dogs and 0.11 mg / kg BW for cats,

[0108] The daily amount ranges from about 0.01 mg to about 0.1 mg of biotin per kg of body weight of the pet animal,

[0109] The daily amount ranges from about 0.001 mg to about 5 mg, preferably 0.015 mg / kg BW for dogs and 0.002 mg / kg BW for cats, of vitamin B12 per kg body weight of the pet animal.

[0110] In one embodiment, the present invention relates to a nutritional composition as described above, wherein the subject is an individual at risk of or suffering from renal failure, renal dysfunction and / or renal disease.

[0111] In one embodiment, the present invention relates to a nutritional composition as described above, wherein the individual is a human, livestock or a pet.

[0112] In one embodiment, the present invention relates to a nutritional composition as described above, wherein muscle loss is associated with renal failure, renal dysfunction or / and renal disease.

[0113] In one embodiment, the present invention relates to a nutritional composition as described above, wherein renal failure, renal dysfunction or / and renal disease is selected from the list of chronic kidney disease, protein energy wasting, end stage renal disease, renal failure due to hospitalization in an intensive care unit, acute kidney injury.

[0114] In one embodiment, the present invention relates to a nutritional composition as described above, wherein the disease or condition associated with muscle wasting is selected from the list consisting of muscle wasting, muscle loss due to renal failure or dysfunction, muscle wasting associated with chronic kidney disease, muscle loss due to hospitalization in an intensive care unit during renal failure, metabolic acidosis during chronic kidney disease, protein energy wasting, or a combination thereof.

[0115] In one embodiment, the invention relates to a nutritional composition as described above, comprising at least three ingredients selected from said group.

[0116] In one embodiment, the invention relates to a nutritional composition as described above, comprising at least four ingredients selected from said group.

[0117] In one embodiment, the invention relates to a nutritional composition as described above, comprising at least five ingredients selected from said group.

[0118] In one embodiment, the invention relates to a nutritional composition as described above, comprising at least six ingredients selected from said group.

[0119] In one embodiment, the invention relates to a nutritional composition as described above, comprising at least seven ingredients selected from said group.

[0120] In one embodiment, the invention relates to a nutritional composition as described above, comprising at least eight ingredients selected from said group.

[0121] In one embodiment, the invention relates to a nutritional composition as described above, comprising at least nine ingredients selected from said group.

[0122] In one embodiment, the invention relates to a nutritional composition as described above, comprising at least ten ingredients selected from said group.

[0123] In one embodiment, the invention relates to a nutritional composition as described above, comprising at least eleven ingredients selected from said group.

[0124] In one embodiment, the invention relates to a nutritional composition as described above, comprising at least twelve ingredients selected from said group.

[0125] In one embodiment, the present invention relates to a nutritional composition as described above for improving the level of at least one amino acid.

[0126] In one embodiment, the invention relates to a nutritional composition as described above, wherein the at least one amino acid is selected from the group consisting of leucine, lysine, arginine, methionine and glutamine.

[0127]

[00136] The nutritional compositions as disclosed herein may be administered using any of a variety of formulations.

[0128] In a preferred embodiment, the administration preparation is the various formula products, foods and food products mentioned above for oral administration.

[0129] The compositions of the present disclosure may include any additional or alternative ingredients, components, or limitations described herein or otherwise useful in a diet.

[0130] One skilled in the art will determine the appropriate amounts of the above nutrients, metabolic precursors or metabolites thereof to achieve their maximum permitted levels in the nutritional composition after administration.

[0131] In one embodiment, the present invention relates to a method for preventing and / or treating a disease or condition associated with muscle deterioration, the method comprising administering to a subject in need thereof an effective amount of a nutritional composition as described above.

[0132] In one embodiment, the invention relates to a method as described above, wherein the subject is an individual at risk of or suffering from renal failure, renal dysfunction and / or renal disease.

[0133] In one embodiment, the invention relates to a method as described above, wherein the muscle loss is associated with renal failure, renal dysfunction and / or renal disease.

[0134] In one embodiment, the invention relates to a method as described above, wherein renal failure, renal dysfunction or / and renal disease is selected from the list of chronic kidney disease, protein energy wasting, end stage renal disease, renal failure due to hospitalization in an intensive care unit, acute kidney injury.

[0135] In one embodiment, the present invention relates to a method as described above, wherein the disease or condition associated with muscle wasting is selected from the list consisting of muscle wasting, muscle loss due to renal failure or dysfunction, muscle wasting associated with chronic kidney disease, muscle loss due to hospitalization in an intensive care unit during renal failure, metabolic acidosis during chronic kidney disease, protein energy wasting, or a combination thereof.

[0136] In one embodiment, the invention relates to a method as described above, which method improves the level of at least one amino acid.

[0137] In one embodiment the invention relates to a method as described above, wherein the at least one amino acid is selected from the group consisting of leucine, lysine, arginine, methionine, glutamine.

[0138] Health Effects

[0139] The health effects of the invention can be preventative, e.g., preventing a failure in protein production, thereby preventing a muscle wasting condition, or curative, e.g., treating a disease or condition associated with muscle wasting in a subject at risk for or suffering from a renal condition, such as muscle wasting, muscle loss due to renal failure or dysfunction, muscle wasting associated with chronic kidney disease, muscle loss due to hospitalization in an intensive care unit during renal failure, metabolic acidosis during chronic kidney disease, protein energy wasting, or a combination thereof.

[0140] The composition of the present invention comprises specific ingredients that affect the improvement of amino acid levels in the human body, which are key nutrients for muscle repair and growth, while delivering energy to the muscles in the body and inhibiting the loss of muscle protein.

[0141] These beneficial effects are particularly important in subjects with renal failure and / or renal disease, such as chronic kidney disease, protein energy wasting, end-stage renal disease, renal failure due to hospitalization in an intensive care unit, acute kidney injury, who experience high and sustained losses of AA that can be shown in the urine, which leads to a failure of muscle protein synthesis and, as a result, muscle deterioration, such as loss of muscle mass and muscle wasting.

[0142] Other advantages of the present invention are improved muscle endurance and / or efficiency, muscle fiber size and reduced muscle atrophy.

[0143] Thus, the benefits of the present invention are to maintain protein production, prevent muscle mass loss and muscle wasting, maintain healthy muscle mass, and treat muscle deterioration and disease in subjects with renal disorders.

[0144] Example

[0145] The following non-limiting examples generally illustrate the basic concepts of the embodiments disclosed herein.

[0146] Figure 1a Urinary leucine levels measured in mice after 8 weeks of treatment with a renal protective blend (RPB) are shown, compared to a vehicle group (diabetic, db / db+V group) and a control group (healthy, db / m+V group) after 8 weeks of treatment with 100 μl of 0.5% carboxymethylcellulose. Urinary leucine levels were determined using liquid-liquid extraction with 13C-yeast as an internal standard. 20 μL of urine was directly extracted in 1300 μL of cold methanol: water: chloroform (5: 3: 5 (v / v)). All samples were stirred at 1500 rpm and 4°C for 10 minutes in an oscillator (Thermomixer C, Eppendorf), followed by centrifugation at 15,000 rpm for 10 minutes at 4°C. Two phases were obtained after the centrifugation step: an upper phase containing polar metabolites and a lower phase containing non-polar metabolites. In addition, a protein layer was retained 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 60% (v / v) acetonitrile: water before analysis. The protein layer was quantitatively determined by bicinchoninic acid (BCA) determination (Thermo Fisher Scientific), and used to normalize metabolite concentrations subsequently. Two microliters of each sample were injected into a hydrophilic interaction chromatography (HILIC) analytical column. Separation was achieved by applying a linear solvent gradient. As mobile phase, solvent A was H2O with 10 mM ammonium acetate (NH4Ac) and 0.04% (v / v) ammonium hydroxide (NH4OH), pH was about 9.3, and solvent B was acetonitrile (ACN). The eluted metabolite leucine was analyzed with an orbital trap mass spectrometer (Orbitrap FusionLumos Tribrid, Thermo Scientific) equipped with a heated electrospray ionization (H-ESI) source. Instant alternating negative (3 kV) and positive (3.5 kV) ion modes were used for ionization. The software Xcalibur v4.1.31.9 (Thermo Scientific) was used for instrument control, data acquisition, and processing.

[0147] The data showed that urinary leucine levels were significantly reduced in mice treated with RPB compared with diabetic controls, which translated into better reabsorption by the kidneys through proximal tubule cells to maintain the beneficial effects of circulating doses of leucine on the muscle.

[0148] Figure 1b Plasma leucine levels measured in mice after 8 weeks of treatment with a renal protective blend (RPB) are shown, compared to a vehicle group (diabetic, db / db+V group) and a control group (healthy, db / m+V group) after 8 weeks of treatment with 100 μl of 0.5% carboxymethylcellulose. Plasma leucine levels were determined using liquid-liquid extraction with 13C-yeast as an internal standard. 20 μL of urine was directly extracted in 1300 μL of cold methanol: water: chloroform (5: 3: 5 (v / v)). All samples were stirred at 1500 rpm and 4°C for 10 minutes in an oscillator (Thermomixer C, Eppendorf), followed by centrifugation at 15,000 rpm for 10 minutes at 4°C. Two phases were obtained after the centrifugation step: an upper phase containing polar metabolites and a lower phase containing non-polar metabolites. In addition, a protein layer was retained 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 60% (v / v) acetonitrile: water before analysis. The protein layer was quantitatively determined by bicinchoninic acid (BCA) determination (Thermo Fisher Scientific), and used to normalize metabolite concentrations subsequently. Two microliters of each sample were injected into a hydrophilic interaction chromatography (HILIC) analytical column. Separation was achieved by applying a linear solvent gradient. As mobile phase, solvent A was H2O with 10 mM ammonium acetate (NH4Ac) and 0.04% (v / v) ammonium hydroxide (NH4OH), pH was about 9.3, and solvent B was acetonitrile (ACN). The eluted metabolite leucine was analyzed with an orbital trap mass spectrometer (Orbitrap FusionLumos Tribrid, Thermo Scientific) equipped with a heated electrospray ionization (H-ESI) source. Instant alternating negative (3 kV) and positive (3.5 kV) ion modes were used for ionization. The software Xcalibur v4.1.31.9 (Thermo Scientific) was used for instrument control, data acquisition, and processing.

[0149] The data showed no differences between mice treated with RPB and diabetic controls.

[0150] Figure 2aUrinary lysine levels measured in mice after 8 weeks of treatment with renal protective blend (RPB) are shown, compared with vehicle group (diabetic, db / db+V group) and control group (healthy, db / m+V group) after 8 weeks of treatment with 100 μl 0.5% carboxymethylcellulose. Urinary lysine levels were determined using liquid-liquid extraction with 13C-yeast as internal standard. 20 μL of urine was directly extracted in 1300 μL of cold methanol: water: chloroform (5: 3: 5 (v / v)). All samples were stirred at 1500 rpm and 4°C for 10 minutes in an oscillator (Thermomixer C, Eppendorf), followed by centrifugation at 15,000 rpm for 10 minutes at 4°C. Two phases were obtained after the centrifugation step: an upper phase containing polar metabolites and a lower phase containing non-polar metabolites. In addition, a protein layer was retained 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 60% (v / v) acetonitrile: water before analysis. The protein layer was quantified with bicinchoninic acid (BCA) assay (ThermoFisherScientific) and used to normalize metabolite concentrations subsequently. Two microliters of each sample were injected into a hydrophilic interaction chromatography (HILIC) analytical column. Separation was achieved by applying a linear solvent gradient. As mobile phase, solvent A was H2O with 10 mM ammonium acetate (NH4Ac) and 0.04% (v / v) ammonium hydroxide (NH4OH), pH was about 9.3, and solvent B was acetonitrile (ACN). The eluted metabolite lysine was analyzed with an orbital trap mass spectrometer (Orbitrap FusionLumos Tribrid, Thermo Scientific) equipped with a heated electrospray ionization (H-ESI) source. Instant alternating negative (3 kV) and positive (3.5 kV) ion modes were used for ionization. The software Xcalibur v4.1.31.9 (Thermo Scientific) was used for instrument control, data acquisition, and processing.

[0151] The data showed that urinary lysine levels were significantly reduced in mice treated with RPB compared with diabetic controls, which translated into better reabsorption by the kidneys through proximal tubule cells to maintain the beneficial effects of circulating doses of lysine on the muscles.

[0152] Figure 2bPlasma lysine levels measured in mice after 8 weeks of treatment with a renal protective blend (RPB) are shown, compared to a vehicle group (diabetic, db / db+V group) and a control group (healthy, db / m+V group) after 8 weeks of treatment with 100 μl of 0.5% carboxymethylcellulose. Plasma lysine levels were determined using liquid-liquid extraction with 13C-yeast as an internal standard. 20 μL of urine was directly extracted in 1300 μL of cold methanol: water: chloroform (5: 3: 5 (v / v)). All samples were stirred at 1500 rpm and 4°C for 10 minutes in an oscillator (Thermomixer C, Eppendorf), followed by centrifugation at 15,000 rpm for 10 minutes at 4°C. Two phases were obtained after the centrifugation step: an upper phase containing polar metabolites and a lower phase containing non-polar metabolites. In addition, a protein layer was retained 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 60% (v / v) acetonitrile: water before analysis. The protein layer was quantified with bicinchoninic acid (BCA) assay (ThermoFisherScientific) and used to normalize metabolite concentrations subsequently. Two microliters of each sample were injected into a hydrophilic interaction chromatography (HILIC) analytical column. Separation was achieved by applying a linear solvent gradient. As mobile phase, solvent A was H2O with 10 mM ammonium acetate (NH4Ac) and 0.04% (v / v) ammonium hydroxide (NH4OH), pH was about 9.3, and solvent B was acetonitrile (ACN). The eluted metabolite lysine was analyzed with an orbital trap mass spectrometer (Orbitrap FusionLumos Tribrid, Thermo Scientific) equipped with a heated electrospray ionization (H-ESI) source. Instant alternating negative (3 kV) and positive (3.5 kV) ion modes were used for ionization. The software Xcalibur v4.1.31.9 (Thermo Scientific) was used for instrument control, data acquisition, and processing.

[0153] The data showed no differences between mice treated with RPB and diabetic controls.

[0154] Figure 3aUrinary arginine levels measured in mice after 8 weeks of treatment with a renal protective blend (RPB) are shown, compared to a vehicle group (diabetic, db / db+V group) and a control group (healthy, db / m+V group) after 8 weeks of treatment with 100 μl of 0.5% carboxymethylcellulose. Urinary arginine levels were determined using liquid-liquid extraction with 13C-yeast as an internal standard. 20 μL of urine was directly extracted in 1300 μL of cold methanol: water: chloroform (5: 3: 5 (v / v)). All samples were stirred at 1500 rpm and 4°C for 10 minutes in an oscillator (Thermomixer C, Eppendorf), followed by centrifugation at 15,000 rpm for 10 minutes at 4°C. Two phases were obtained after the centrifugation step: an upper phase containing polar metabolites and a lower phase containing non-polar metabolites. In addition, a protein layer was retained 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 60% (v / v) acetonitrile: water before analysis. The protein layer was quantitatively determined by bicinchoninic acid (BCA) determination (ThermoFisherScientific), and used to normalize metabolite concentrations subsequently. Two microliters of each sample were injected into a hydrophilic interaction chromatography (HILIC) analytical column. Separation was achieved by applying a linear solvent gradient. As mobile phase, solvent A was H2O with 10 mM ammonium acetate (NH4Ac) and 0.04% (v / v) ammonium hydroxide (NH4OH), pH was about 9.3, and solvent B was acetonitrile (ACN). The eluted metabolite arginine was analyzed with an orbital trap mass spectrometer (Orbitrap FusionLumos Tribrid, Thermo Scientific) equipped with a heated electrospray ionization (H-ESI) source. Instant alternating negative (3 kV) and positive (3.5 kV) ion modes were used for ionization. The software Xcalibur v4.1.31.9 (Thermo Scientific) was used for instrument control, data acquisition, and processing.

[0155] The data showed that urinary arginine levels were significantly increased in mice treated with RPB compared to diabetic controls due to the presence of arginine supplementation in the blend.

[0156] Figure 3bPlasma arginine levels measured in mice after 8 weeks of treatment with a renal protective blend (RPB) are shown, compared to a vehicle group (diabetic, db / db+V group) and a control group (healthy, db / m+V group) after 8 weeks of treatment with 100 μl of 0.5% carboxymethylcellulose. Plasma arginine levels were determined using liquid-liquid extraction with 13C-yeast as an internal standard. 20 μL of urine was directly extracted in 1300 μL of cold methanol: water: chloroform (5: 3: 5 (v / v)). All samples were stirred at 1500 rpm and 4°C for 10 minutes in an oscillator (Thermomixer C, Eppendorf), followed by centrifugation at 15,000 rpm for 10 minutes at 4°C. Two phases were obtained after the centrifugation step: an upper phase containing polar metabolites and a lower phase containing non-polar metabolites. In addition, a protein layer was retained 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 60% (v / v) acetonitrile: water before analysis. The protein layer was quantitatively determined by bicinchoninic acid (BCA) determination (ThermoFisherScientific), and used to normalize metabolite concentrations subsequently. Two microliters of each sample were injected into a hydrophilic interaction chromatography (HILIC) analytical column. Separation was achieved by applying a linear solvent gradient. As mobile phase, solvent A was H2O with 10 mM ammonium acetate (NH4Ac) and 0.04% (v / v) ammonium hydroxide (NH4OH), pH was about 9.3, and solvent B was acetonitrile (ACN). The eluted metabolite arginine was analyzed with an orbital trap mass spectrometer (Orbitrap FusionLumos Tribrid, Thermo Scientific) equipped with a heated electrospray ionization (H-ESI) source. Instant alternating negative (3 kV) and positive (3.5 kV) ion modes were used for ionization. The software Xcalibur v4.1.31.9 (Thermo Scientific) was used for instrument control, data acquisition, and processing.

[0157] The data showed that plasma arginine was significantly increased in mice treated with RPB compared to diabetic controls. RPB supplementation rescued the arginine depletion present in diabetic conditions.

[0158] Figure 4aUrinary methionine levels measured in mice after 8 weeks of treatment with renal protective blend (RPB) compared to vehicle group (diabetic, db / db+V group) and control group (healthy, db / m+V group) after 8 weeks of treatment with 100 μl 0.5% carboxymethylcellulose are shown. Urinary methionine levels were determined using liquid-liquid extraction with 13C-yeast as internal standard. 20 μL of urine was directly extracted in 1300 μL of cold methanol: water: chloroform (5: 3: 5 (v / v)). All samples were stirred at 1500 rpm and 4°C for 10 minutes in an oscillator (Thermomixer C, Eppendorf), followed by centrifugation at 15,000 rpm for 10 minutes at 4°C. Two phases were obtained after the centrifugation step: an upper phase containing polar metabolites and a lower phase containing non-polar metabolites. In addition, a protein layer was retained 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 60% (v / v) acetonitrile: water before analysis. The protein layer was quantified with bicinchoninic acid (BCA) assay (Thermo Fisher Scientific) and used to normalize metabolite concentrations subsequently. Two microliters of each sample were injected into a hydrophilic interaction chromatography (HILIC) analytical column. Separation was achieved by applying a linear solvent gradient. As mobile phase, solvent A was H2O with 10 mM ammonium acetate (NH4Ac) and 0.04% (v / v) ammonium hydroxide (NH4OH), pH was about 9.3, and solvent B was acetonitrile (ACN). The eluted metabolite methionine was analyzed with an orbital trap mass spectrometer (Orbitrap FusionLumos Tribrid, Thermo Scientific) equipped with a heated electrospray ionization (H-ESI) source. Instant alternating negative (3 kV) and positive (3.5 kV) ion modes were used for ionization. The software Xcalibur v4.1.31.9 (Thermo Scientific) was used for instrument control, data acquisition, and processing.

[0159] The data showed that urinary methionine levels were significantly reduced in mice treated with RPB compared with diabetic controls, returning to healthy control levels, and that reducing methionine from the body or diet was associated with health benefits.

[0160] Figure 4bPlasma methionine levels measured in mice after 8 weeks of treatment with renal protective blend (RPB) compared to vehicle group (diabetic, db / db+V group) and control group (healthy, db / m+V group) after 8 weeks of treatment with 100 μl 0.5% carboxymethylcellulose are shown. Plasma methionine levels were determined using liquid-liquid extraction with 13C-yeast as internal standard. 20 μL of urine was directly extracted in 1300 μL of cold methanol: water: chloroform (5:3:5 (v / v)). All samples were stirred at 1500 rpm and 4°C for 10 minutes in an oscillator (Thermomixer C, Eppendorf), followed by centrifugation at 15,000 rpm for 10 minutes at 4°C. Two phases were obtained after the centrifugation step: an upper phase containing polar metabolites and a lower phase containing non-polar metabolites. In addition, a protein layer was retained 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 60% (v / v) acetonitrile: water before analysis. The protein layer was quantified with bicinchoninic acid (BCA) assay (ThermoFisher Scientific) and used to normalize metabolite concentrations subsequently. Two microliters of each sample were injected into a hydrophilic interaction chromatography (HILIC) analytical column. Separation was achieved by applying a linear solvent gradient. As mobile phase, solvent A was H2O with 10 mM ammonium acetate (NH4Ac) and 0.04% (v / v) ammonium hydroxide (NH4OH), pH was about 9.3, and solvent B was acetonitrile (ACN). The eluted metabolite methionine was analyzed with an orbital trap mass spectrometer (Orbitrap Fusion Lumos Tribrid, Thermo Scientific) equipped with a heated electrospray ionization (H-ESI) source. Instant alternating negative (3 kV) and positive (3.5 kV) ion modes were used for ionization. The software Xcalibur v4.1.31.9 (Thermo Scientific) was used for instrument control, data acquisition, and processing.

[0161] The data showed a strong trend toward decreased plasma methionine levels in mice treated with RPB compared to diabetic controls, consistent with the fact that reducing methionine from the body or diet is associated with health benefits.

[0162] Figure 5Urinary glutamine levels measured in mice after 8 weeks of treatment with renal protective blend (RPB) compared to vehicle group (diabetic, db / db+V group) and control group (healthy, db / m+V group) after 8 weeks of treatment with 100 μl 0.5% carboxymethylcellulose are shown. Urinary glutamine levels were determined using liquid-liquid extraction with 13C-yeast as an internal standard. 20 μL of urine was directly extracted in 1300 μL of cold methanol: water: chloroform (5: 3: 5 (v / v)). All samples were stirred at 1500 rpm and 4°C for 10 minutes in an oscillator (Thermomixer C, Eppendorf), followed by centrifugation at 15,000 rpm for 10 minutes at 4°C. Two phases were obtained after the centrifugation step: an upper phase containing polar metabolites and a lower phase containing non-polar metabolites. In addition, a protein layer was retained 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 60% (v / v) acetonitrile: water before analysis. The protein layer was quantified with bicinchoninic acid (BCA) assay (Thermo Fisher Scientific) and used to normalize metabolite concentrations subsequently. Two microliters of each sample were injected into a hydrophilic interaction chromatography (HILIC) analytical column. Separation was achieved by applying a linear solvent gradient. As mobile phase, solvent A was H2O with 10 mM ammonium acetate (NH4Ac) and 0.04% (v / v) ammonium hydroxide (NH4OH), pH was about 9.3, and solvent B was acetonitrile (ACN). The eluted metabolite glutamine was analyzed with an orbital trap mass spectrometer (Orbitrap FusionLumos Tribrid, Thermo Scientific) equipped with a heated electrospray ionization (H-ESI) source. Instant alternating negative (3 kV) and positive (3.5 kV) ion modes were used for ionization. The software Xcalibur v4.1.31.9 (Thermo Scientific) was used for instrument control, data acquisition, and processing.

[0163] The data showed a trend toward decreased urinary glutamine levels in mice treated with RPB compared with diabetic controls.

[0164] This preclinical study demonstrates that ingestion of the nutritional compositions disclosed herein prevents the loss of key amino acids for muscle protein, thereby preventing and / or treating diseases or conditions associated with muscle deterioration, particularly in subjects at risk of or suffering from renal failure, renal dysfunction, or / and renal disease, such as CKD, protein energy wasting, ESRD, renal failure due to hospitalization in an ICU, AKI.

[0165] It should be understood that various changes and modifications made to the presently preferred embodiments described herein will be apparent to those skilled in the art. These changes and modifications may be made without departing from the spirit and scope of the subject matter of the present invention and without diminishing its intended advantages. Therefore, such changes and modifications are intended to be covered by the appended claims.

Claims

1. A nutritional composition for preventing and / or treating a disease or condition associated with muscle wasting in a subject in need thereof, the nutritional composition comprising 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, Vitamin B12.

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

3. The nutritional composition according to any one of the preceding claims, wherein the subject is an individual at risk of or suffering from renal failure, renal dysfunction and / or renal disease.

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

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

6. Nutritional composition according to any of the preceding claims, wherein the renal failure, the renal dysfunction or / and the renal disease is selected from the list of chronic kidney disease, protein energy wasting, end stage renal disease, renal failure due to hospitalization in an intensive care unit, acute kidney injury.

7. The nutritional composition according to any of the preceding claims, wherein the disease or condition associated with muscle wasting is selected from the list consisting of muscle wasting, muscle loss due to renal failure or dysfunction, muscle wasting associated with chronic kidney disease, muscle loss due to hospitalization in an intensive care unit during renal failure, metabolic acidosis during chronic kidney disease, protein energy wasting, or a combination thereof.

8. The nutritional composition according to any one of the preceding claims, comprising at least three, or at least four, or at least five, or at least six, or at least seven, or at least eight, or at least nine, or at least ten, or at least eleven, or at least twelve ingredients selected from said group.

9. The nutritional composition according to any one of the preceding claims for improving the level of at least one amino acid.

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

11. A method for preventing and / or treating a disease or condition associated with muscle deterioration, the method comprising administering to a subject in need thereof an effective amount of a nutritional composition according to any one of the preceding claims.

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

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

14. The method according to any one of claims 11 or claim 13, wherein the renal failure, the renal dysfunction or / and the renal disease is selected from the list of chronic kidney disease, protein energy wasting, end-stage renal disease, renal failure due to hospitalization in an intensive care unit, acute kidney injury.

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

16. The method of any one of claims 11 to 15, which improves the level of at least one amino acid.

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

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