Compositions comprising urolithin compounds

Abstract

The present invention provides compositions comprising a protein source and urolithin. The invention also provides uses and methods related to or utilizing such compositions, such as medicaments, dietary supplements, functional foods or medical foods, for treating and / or preventing muscle-related pathological conditions. The invention also provides a kit comprising urolithin and a protein.

Description

[0001] This application is a divisional application of a Chinese patent application with the application number 201680050455.1 (International Application Number PCT / EP2016 / 070257), the filing date of August 26, 2016, and the invention title of "Compositions Comprising Urolithin Compounds". Technical Field

[0002] The present invention relates to nutritional and pharmaceutical formulations of urolithin and proteins (specifically urolithin A and proteins). Background Art

[0003] Low muscle mass or poor muscle performance is characteristic of many diseases and conditions.

[0004] Muscle-related pathological conditions include myopathy, neuromuscular diseases such as Duchenne muscular dystrophy, acute sarcopenia such as muscle atrophy and / or cachexia such as associated with burns, bed rest, limb immobilization or thoracic, abdominal, neck and / or orthopedic surgery. Age-related muscle loss is a particularly prevalent condition. Cachexia due to long-term immobilization or other diseases such as cancer are other conditions typically characterized by poor muscle performance.

[0005] Good muscle performance is important for an effective life at all stages of life for healthy individuals as well as those with diseases (especially the elderly). Improved muscle performance is of particular interest to athletes. For example, an increase in muscle contraction strength, an increase in muscle contraction amplitude or a shortening of the muscle reaction time between stimulation and contraction are all beneficial to an individual, especially an athlete.

[0006] In severe cases of muscle atrophy, anabolic steroids such as methandrostenolone are administered to patients to aid the healing process. Such drugs can have a number of side effects, so it is preferably to avoid their long-term use.

[0007] Since the lack of muscle-building amino acids can cause muscle wasting, amino acid therapy is beneficial for regenerating damaged or atrophied muscle tissue and for building muscle mass. In addition to lysine and other amino acids, branched-chain amino acids or BCAA (leucine, isoleucine and valine) are very important for this process.

[0008] Protein-containing nutritional products are available and are specifically formulated to increase muscle mass, improve muscle performance, and / or reduce muscle wasting in elderly or hospitalized individuals. In general, regular exercise is necessary for the desired improvements to be achieved. Summary of the Invention

[0009] The present invention provides a composition comprising:

[0010] a) a protein source; and

[0011] b) a compound of formula (I) or a salt thereof:

[0012]

[0013] wherein:

[0014] A, B, C, and D are each independently selected from H and OH;

[0015] W, X, and Y are each independently selected from H and OH; and

[0016] Z is selected from H and OH.

[0017] The compound of formula (I) is a member of the Urolithin family; specifically, the compound of formula (I) is urolithin A. It has been found that administering a composition of protein and urolithin A has surprisingly beneficial and enhanced effects compared to administering the protein alone. Accordingly, the compositions of the present invention are suitable for treating diseases and conditions characterized by low muscle mass or poor muscle performance and are suitable for enhancing muscle growth and / or muscle performance. It is also suitable for maintaining muscle function.

[0018] In general, exercise is necessary for an individual for optimal amino acid / protein therapy. There are indications that the compositions of the present invention are effective in enhancing muscle function in the absence of exercise or with less necessary exercise.

[0019] The present invention further provides the compositions of the present invention for treating muscle-related pathological conditions. The present invention also provides a method of treating a muscle-related pathological condition in an individual, the method comprising administering to the individual an effective amount of the composition of the present invention. The present invention provides the compositions of the present invention for enhancing muscle performance. The present invention also provides a method of enhancing muscle performance by administering to an individual an effective amount of the composition of the present invention.

[0020] In the treatment of the present invention, it is not necessary to administer urolithin and protein simultaneously as part of a single composition. The present invention also provides a method for treating a muscle-related pathological condition of an individual or improving the muscle function of an individual, the method comprising administering to the individual an effective amount of urolithin (such as urolithin A) and an effective amount of protein. The urolithin and protein can be administered simultaneously or at intervals. The present invention further provides a kit comprising urolithin and protein for such methods. The amount of each of the urolithin and protein administered is as described below for the unit dose of the composition of the present invention.

[0021] The present invention further provides D 50 having a size in the range of 0.5 to 50 μm and D 90 a compound of formula (I) or a salt thereof having a size in the range of 5 to 100 μm. Preferably, the compound or salt has a D 90 size in the range of 8.2 to 16.0 μm, D 50 size in the range of 2.8 to 5.5 μm, and D 10 size in the range of 0.5 to 1.0 μm. It has been found that the compounds of the present invention having those particle sizes have good dispersion and dissolution properties and improved bioavailability. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 Showing the results of a muscle endurance experiment in which mice were fed either a high-protein diet alone or a high-protein diet containing urolithin A.

[0023] Figure 2 Showing the results of an experiment in which rats were fed a preparation containing urolithin A in a variety of different particle sizes and the urolithin A content in the blood was evaluated. DETAILED DESCRIPTION

[0024] As described above, the present invention provides a composition comprising a protein source and urolithin.

[0025] The protein in the composition of the present invention is preferably a purified protein; that is, it has been isolated from the natural food components in which it is formed. Evaluated by weight%, the protein content in the composition of the present invention is preferably higher than that in most untreated food components. The protein generally constitutes at least 15% w / w of the composition of the present invention. The protein preferably constitutes 20% w / w or more of the composition, such as 25% w / w or more by weight, such as 30% w / w or more by weight, such as 40% w / w or more, such as 50% w / w or more, such as 55% w / w or more, such as 60% w / w or more of the composition. For example, the protein can constitute 20 - 99% w / w of the composition, such as 20 - 90% w / w of the composition, such as 30 - 80% / w of the composition, such as 40 - 80% / w of the composition, such as 50 - 80% / w of the composition, such as 40 - 70% / w of the composition.

[0026] The weight ratio between the protein component and urolithin is generally in the range of 3:1 to 5000:1, such as 3:1 to 1000:1, such as 5:1 to 1000:1; such as 3:1 to 500:1, such as 3:1 to 250:1, such as 5:1 to 500:1; such as 5:1 to 200:1; such as 5:1 to 100:1; such as 5:1 to 50:1; such as 5:1 to 20:1, such as 6:1 to 15:1. Alternatively, the ratio can be, for example, in the range of 10:1 to 500:1, such as in the range of 10:1 to 100:1, such as 20:1 to 50:1, such as 30:1 to 40:1. In some embodiments, the ratio can be in the range of 50:1 to 5000:1, such as 70:1 to 2000:1, such as 100:1 to 500:1. The composition of the present invention can be provided as a single - serving supplement (such as a bar or a beverage) to an individual's general diet; alternatively, it can be provided as part or all of each meal. If the composition is provided as part or all of each meal, then the weight ratio between the protein component and urolithin is generally higher than when the composition is provided as a single - serving supplement to an individual's general diet.

[0027] Urolithin generally constitutes 0.05 to 10% w / w of the composition of the present invention, such as 0.1 to 10% w / w. For example, urolithin can constitute 0.2 - 8% w / w of the composition, such as 0.2 - 5% w / w of the composition, such as 0.3 - 3% / w of the composition, such as 0.5 - 2% w / w of the composition. In some embodiments, urolithin can constitute 0.05 - 5% w / w of the composition, such as 0.1 - 2% w / w of the composition, such as 0.2 - 1% / w of the composition. In some embodiments, urolithin can constitute 0.05 to 80% w / w of the composition, such as 0.1 to 75% w / w of the composition.

[0028] Protein source:

[0029] Non-limiting examples of suitable proteins or their sources for the composition include hydrolyzed, partially hydrolyzed or non-hydrolyzed proteins or protein sources.

[0030] It can be derived from any known or otherwise suitable source, such as milk (e.g., casein, whey), animals (e.g., meat, fish), cereals (e.g., rice, corn) or plants (e.g., soybeans, peas) sources. Combinations of protein sources or types can be used. Non-limiting examples of proteins or their sources include whole pea protein, whole pea protein isolate, whole pea protein concentrate, milk protein isolate, milk protein concentrate, casein protein isolate, casein protein concentrate, whey protein concentrate, whey protein isolate, sodium caseinate or calcium caseinate, whole milk, partially or fully skimmed milk, yogurt, soy protein isolate and soy protein concentrate and combinations thereof. Combinations of protein sources or types can be used.

[0031] Preferred proteins include pea protein, whey protein, soy protein and casein. Casein proteins can be, for example, or include sodium caseinate and calcium caseinate.

[0032] Mixtures of protein sources can have specific benefits. For example, two or more of pea protein, whey protein, soy protein and casein can be present. For example, sodium caseinate, milk protein concentrate and soy protein isolate can all be present. A combination of casein protein and whey protein is particularly preferred, for example containing 60 to 90% w / w whey protein and 10 to 40% w / w casein protein, for example 65 to 80% w / w whey protein and 20 to 35% w / w casein protein, for example 70% w / w whey protein and 30% w / w casein protein.

[0033] The protein source can be provided by individual amino acids or polypeptides composed of multiple amino acids or mixtures of those.

[0034] For many muscle growth, muscle maintenance and / or muscle enhancement treatments, providing certain specific amino acids is beneficial. For example, L-arginine, L-glutamine, lysine and branched-chain amino acids (i.e., leucine, isoleucine and valine; specifically leucine and isoleucine) are considered important. In certain embodiments, the protein source contains a high proportion of those amino acids.

[0035] These specific amino acids can be provided as a protein source or they can be attached to the main source of protein. Thus, the protein source in the compositions of the present invention can include one or more branched-chain amino acids (leucine, isoleucine, and valine). The protein source in the compositions of the present invention can include one or both of L-arginine and L-glutamine. The protein source in the compositions of the present invention can include lysine.

[0036] In preferred compositions, the protein component comprises whey protein and / or casein protein together with one or more individual amino acids, such as one or more (or all) of leucine, isoleucine, and L-arginine.

[0037] Urolithin:

[0038] Urolithin is a metabolite produced by the activity of mammalian (including human) gut microbiota on ellagitannin and ellagic acid. Ellagitannin and ellagic acid are compounds commonly found in foods such as pomegranates, nuts, and berries. Ellagitannin is minimally absorbed in the gut itself. Urolithin is a class of compounds having the representative structure (I) shown above. The structures of certain particularly common urolithins are described in Table 1 below, see structure (I).

[0039]

[0040] In practice, for commercial scale products, it is convenient to synthesize urolithin.

[0041] The synthetic pathway is described, for example, in WO2014 / 004902.

[0042] Particularly suitable compounds for the compositions of the present invention are naturally occurring urolithins. Thus, Z is preferably OH and W, X, and Y are preferably all H. When W, X, and Y are all H, and A, and B are both H, and C, D, and Z are all OH, then the compound is urolithin C. When W, X, and Y are all H, and A, B, and C are all H, and D and Z are OH, then the compound is urolithin A. Preferably, the urolithin for the formulations of the present invention is urolithin A or urolithin C. Most preferably, the urolithin for the formulations of the present invention is urolithin A.

[0043]

[0044] Urolithin A

[0045] Preferably, the urolithin for the compositions of the present invention is micronized. The inventors have found that micronized urolithin can dissolve or suspend more rapidly and effectively than non-micronized urolithin.

[0046] The present invention further provides micronized urolithin. The present invention further provides a composition comprising micronized urolithin. The D 50 size of the micronized urolithin is preferably less than 100 μm - that is, the particle size of 50% by mass of the urolithin is less than 100 μm. More preferably, the D 50 size of the urolithin is less than 75 μm, such as less than 50 μm, such as less than 25 μm, such as less than 20 μm, such as less than 10 μm. More preferably, the D 50 of the urolithin is in the range of 0.5 - 50 μm, such as 0.5 to 20 μm, such as 0.5 to 10 μm, such as 1 to 10 μm, such as 2.8 to 5.5 μm. Preferably, the D 90 size of the urolithin is less than 100 μm - that is, the particle size of 90% by mass of the urolithin is less than 100 μm. More preferably, the D 90 size of the urolithin is less than 75 μm, such as less than 50 μm, such as less than 25 μm, such as less than 20 μm, such as less than 15 μm. The D 90 of the urolithin is preferably in the range of 5 to 100 μm, such as 5 to 50 μm, such as 5 to 20 μm, such as 8.2 to 16.0 μm. Preferably, the D 10 of the urolithin is in the range of 0.5 - 1.0 μm. Preferably, the D 90 of the urolithin is in the range of 8.2 to 16.0 μm, the D 50 is in the range of 2.8 to 5.5 μm, and the D 10 is in the range of 0.5 to 1.0 μm. Micronization can be achieved by methods established in the art, for example, compression force milling, hammermilling, universal or pin milling, or jetmilling (such as spiral jetmilling or fluidized bed jetmilling) can be used. Jetmilling is particularly suitable.

[0047] Form of the composition:

[0048] The composition of the present invention can be in any suitable physical form. It can be in solid (such as flakes or rods), semi-solid (such as soft gels, capsules (such as hard capsules) or dragees), powder or liquid (including emulsions) form. The composition of the present invention can be a pharmaceutical composition. The composition of the present invention can be a nutritional composition.

[0049] The composition in tablet form can be of any suitable type and can contain excipients conventional in the art. The excipients can, for example, provide the required hardness, shelf life, and taste so that the composition has an acceptable taste, an attractive appearance, and good storage stability. The bar can be of any suitable type and can contain ingredients commonly used in the preparation of snack bars.

[0050] The semi - solid form can also contain excipients conventional in the art. The excipients can, for example, provide the required hardness, shelf life, and taste so that the composition has an acceptable taste, an attractive appearance, and good storage stability.

[0051] Powders are commonly used to supply nutritional and medical compositions.

[0052] Powders have the advantage that multiple doses can be provided in a simple container and doses of various sizes can be used from the same supply container. Powders generally have good storage characteristics. Powder compositions can also contain excipients conventional in the art. The excipients can, for example, provide shelf life, taste, and moisture resistance so that the composition has an acceptable taste, an attractive appearance, and good storage stability. Protein powders are widely available on the market. The present invention can take the form of a kit comprising a protein powder composition together with a separate solid or liquid composition containing urolithin. The solid or liquid composition containing urolithin (such as a tablet or a beverage or other forms described herein) can have instructions for use with the protein powder. The present invention can take the form of a protein powder mixed with urolithin.

[0053] The liquid composition can be in the form of a medicine or in the form of a beverage. The liquid preparation can be a solution, an emulsion, a slurry, or other semi - liquid. The excipients in the liquid composition can, for example, provide shelf life, visual appearance, taste, and mouthfeel so that the composition has an acceptable taste, an attractive appearance, and good storage stability.

[0054] The composition may be in the form of yogurt. For example, it is known that Greek and Icelandic style yogurts typically have particularly high protein contents, which makes them particularly suitable for use in the formulations of the present invention. The yogurt for use in the composition of the present invention may contain, for example, 2 to 15 g of protein per 100 g. Yogurts with high protein contents are particularly preferred, such as 6 to 15 g per 100 g, such as 7 to 15 g per 100 g, such as 8 to 15 g per 100 g. The yogurt of the composition of the present invention may be in a form that can be eaten with a spoon or drunk. Optionally, additional protein may also be added to the yogurt formulation to increase the protein content of the formulation. The yogurt of the present invention may contain live cultures, such as Streptococcus thermophilus (S. thermophilus), Lactobacillus bulgaricus (L. bulgaricus) and / or Lactobacillus acidophilus (L. acidophilus), Lactococcus lactis (L. lactis).

[0055] Additional components in the composition of the present invention:

[0056] The composition according to the present invention may contain additional components other than urolithins and proteins. The additional components may be compounds that provide health benefits, such as selected from vitamins, minerals, polyunsaturated fatty acids, functional amino acids and other compounds.

[0057] Among the vitamins, particular mention may be made of vitamin A, vitamin C, vitamin D, vitamin B12 and vitamin K2. As used herein, "vitamin D" refers to any known form of vitamin D and particularly includes vitamin D2 (ergocalciferol), vitamin D3 (cholecalciferol), vitamin D precursors, metabolites and other analogues and combinations thereof, as well as various active and inactive forms of vitamin D. For example, vitamin D3 may be provided in its unhydroxylated inactive form as cholecalciferol, or may be provided in its hydroxylated active form as calcitriol.

[0058] Creatine has been described as having a beneficial effect in the treatment of muscle disorders. It may be included in the composition of the present invention. β-Hydroxy-β-methylbutyrate (HMB) has been described as having a beneficial effect in the treatment of muscle disorders. It may be included in the composition of the present invention.

[0059] Among the minerals, particular mention may be made of calcium salts (such as calcium phosphate), selenium salts and iron salts.

[0060] Polyunsaturated fatty acids are fatty acids that contain more than one double bond in the main chain. This category includes a variety of important compounds, such as essential fatty acids, for example, ω-3 and ω-6 fatty acids. Long-chain polyunsaturated fatty acids are suitable and preferably those having at least 20 carbon atoms in the molecule. Such long-chain ω-3 fatty acids include cis-11,14,17-eicosatrienoic acid (ETE) C20:3, cis-8,11,14,17-eicosatetraenoic acid (ETA) C20:4, cis-5,8,11,14,17-eicosapentaenoic acid (EPA) C20:5, cis-7,10,13,16,19-docosapentaenoic acid (DPA, Clupanodonic acid) C22:5, cis-4,7,10,13,16,19-docosahexaenoic acid (DHA) C22:6, cis-9,12,15,18,21-tetracosapentaenoic acid C24:5; cis-6,9,12,15,18,21-tetracosahexaenoic acid (Nisinic acid) C24:6. Long-chain ω-6 fatty acids having at least 20 carbon atoms include cis-11,14-eicosadienoic acid C20:2, cis-8,11,14-eicosatrienoic acid (dihomo-γ-linolenic acid) (DGLA) C20:3, cis-5,8,11,14-eicosatetraenoic acid (Arachidonic acid) (AA) C20:4, cis-13,16-docosadienoic acid C22:2, cis-7,10,13,16-docosatetraenoic acid (Adrenic acid) C22:4, cis-4,7,10,13,16-docosapentaenoic acid (Osbond acid) C22:5. The composition according to the invention preferably contains EPA, DHA or a combination thereof, for example in an amount of 10 to 1,000 mg; for example in an amount of 25 to 250 mg.

[0061] For a variety of muscle growth and / or muscle enhancement treatments, it is beneficial to provide certain specific amino acids. For example, L-arginine, L-glutamine, lysine and branched-chain amino acids are considered important. These amino acids are sometimes referred to as "functional amino acids". The composition of the invention may include one or more branched-chain amino acids (leucine, isoleucine and valine). The composition of the invention may include one or both of L-arginine and L-glutamine. The composition of the invention may include lysine.

[0062] The pharmaceutical composition of the invention may include additional pharmaceutically active compounds.

[0063] The compositions of the present invention may include one or more reagents suitable for mitochondrial biogenesis or for treating mitochondrial disorders. Such compounds include, but are not limited to, resveratrol, pyrroloquinoline quinone, genistein, hydroxyltyrosol, quercetin, L-carnitine, alpha-lipoic acid, and folinic acid (e.g., as leucovorin).

[0064] Additional compounds may further (or alternatively) be included in the compositions of the present invention, including, for example, tomatidine, ursolic acid, curcumin, capsaicin, menthol, trolamine salicylate, and methyl salicylate.

[0065] In some exemplary embodiments, in addition to proteins and urolithins, the compositions of the present invention may contain one or more additional macronutrients, typically fats or carbohydrates, or both fats and carbohydrates.

[0066] Any suitable source of fats or oils of the types commonly used in the preparation of foodstuffs and pharmaceuticals may be used in the compositions of the present invention. Non-limiting examples of suitable sources of fats for the compositions described herein also include polyunsaturated fatty acids such as docosahexaenoic acid (DHA), arachidonic acid (ARA), eicosapentaenoic acid (EPA), and combinations thereof.

[0067] Non-limiting examples of suitable carbohydrates or their sources for the compositions described herein may include maltodextrin, hydrolyzed or modified starch or corn starch, glucose polymers, corn syrup, corn syrup solids, rice-derived carbohydrates, glucose, fructose, lactose, high fructose corn syrup, tapioca dextrin, isomaltulose, sucromalt, maltitol powder, glycerol, fructooligosaccharides, soy fiber, corn fiber, guar gum, konjac flour, polydextrose, honey, sugar alcohols (e.g., maltitol, erythritol, sorbitol), and combinations thereof. Maltodextrin, sucrose, and fructose are particularly preferred.

[0068] The total concentration or amount of protein, fat, carbohydrates, and other components varies depending on the nutritional needs of the intended user.

[0069] Additional components in the compositions of the present invention may be compounds that do not provide a health benefit to the individual, but rather improve the composition in some other way, such as its taste, texture, or shelf life as mentioned above. The compositions of the present invention may thus further contain one or more compounds selected from the group consisting of emulsifiers, colorants, preservatives, gums, hardeners, thickeners, sweeteners, and flavorants.

[0070] Suitable emulsifiers, colorants, preservatives, gums, hardeners, and thickeners are well known in the art for making emulsions and other semi-liquids. For example, preservatives such as benzoic acid, sorbic acid, phosphoric acid, lactic acid, acetic acid, hydrochloric acid, and their soluble salts may be used.

[0071] Sweeteners may be particularly beneficial in the compositions of the present invention. High-concentration non-nutritive carbohydrate sweeteners may be used, such as those selected from aspartame, sucrose, potassium acesulfame, saccharin, cyclamate, Stevia, thaumatin, and mixtures thereof. Aspartame is particularly suitable.

[0072] Flavoring agents can be particularly beneficial in the compositions of the present invention. In liquid or semi-liquid compositions, fruit flavors can be provided by including jam or puree. Typical flavoring agents include strawberry, raspberry, bilberry, apricot, pomegranate, peach, pineapple, lemon, orange, and apple. Generally, fruit flavoring agents include fruit extracts, fruit preserves, or purees, in combination with any sweeteners, starches, stabilizers, natural and / or artificial flavorings, colorants, preservatives, water, and citric acid or other suitable acids to control the pH.

[0073] Administration

[0074] The effective amount of the composition to be administered will vary depending on the mode of administration, age, weight, and general health of the individual. Factors such as the disease state, age, and weight of the individual can be important, and the dosage regimen can be adjusted to provide an optimal response.

[0075] Conventional protein compositions are typically taken in amounts of 5 to 30 g per serving, and an individual typically takes one, two, or three servings per day. Thus, the daily dose of protein from the composition is typically in the range of 5 to 90 g, such as 5 to 80 g, such as 5 to 70 g, such as 5 to 60 g, such as 5 to 50 g, such as 10 to 40 g, such as 20 to 40 g.

[0076] For elderly individuals, the recommended protein intake and exercise for optimal muscle function have been described, for example, in 'Recommendations from the ESPEN Expert Group': Clinical Nutrition, 33 (2014) 929e936. The recommendations are: (a) for healthy elderly individuals, the diet should provide at least 1.0 - 1.2 g of protein per kilogram of body weight per day; (b) for elderly individuals who are malnourished or at risk of malnutrition due to acute or chronic diseases, the diet should provide 1.2 - 1.5 g of protein per kilogram of body weight per day, and individuals with severe diseases or injuries may require even higher intakes.

[0077] The unit dose composition of the present invention preferably contains 5 to 90 g, such as 5 to 80 g, such as 5 to 70 g, such as 5 to 60 g of protein, such as 5 to 40 g of protein, such as 10 to 40 g of protein, such as 10 to 30 g of protein. The unit dose can be in the form of a snack bar: a snack bar weighing 25 to 150 g (such as 40 to 100 g) can contain the necessary amount of protein (such as 10 to 40 g of protein, or another amount mentioned above). The unit dose composition can alternatively be in the form of a beverage, for example provided in a container (such as a sachet or a bottle) suitable for a single dose volume (such as 50 to 500 ml, such as 100 to 300 ml). A 100 to 300 ml beverage can contain the necessary amount of protein. The unit dose composition can alternatively be in the form of a powder to be reconstituted into a beverage, for example a suitable amount of powder for a single dose (20 gr to 60 gr of powder, containing 10 gr to 40 gr of protein). A 100 to 500 ml reconstituted beverage can contain the necessary amount of protein.

[0078] The daily intake of the urolithin (such as urolithin A) component is generally in the range of 10 mg to 5 g per day, such as 20 mg to 2500 mg per day, such as 20 mg to 500 mg per day, such as 10 mg to 100 mg per day, such as 50 mg to 1500 mg per day, such as 250 mg to 1500 mg per day, such as 50 mg to 1000 mg per day, such as 20 mg to 250 mg per day, such as 250 mg to 1000 mg per day, such as 500 mg to 1000 mg per day, such as 750 mg to 1000 mg per day. In one embodiment, the composition is taken in an amount to provide a dose of urolithin in the range of 0.2 mg / kg / day to greater than about 100 mg / kg / day. For example, the dose of urolithin can be 0.2 to 100, 0.2 to 50, 0.2 to 25, 0.2 to 10, 0.2 to 7.5, 0.2 to 5, 0.25 to 100, 0.25 to 25, 0.25 to 25, 0.25 to 10, 0.25 to 7.5, 0.25 to 5, 0.5 to 50, 0.5 to 25, 0.5 to 20, 0.5 to 15, 0.5 to 10, 0.5 to 7.5, 0.5 to 5, 0.75 to 50, 0.75 to 25, 0.75 to 20, 0.75 to 15, 0.75 to 10, 0.75 to 7.5, 0.75 to 5, 1.0 to 50, 1 to 25, 1 to 20, 1 to 15, 1 to 10, 1 to 7.5, 1 to 5, 2 to 50, 2 to 25, 2 to 20, 2 to 15, 2 to 10, 2 to 7.5 or 2 to 5 mg / kg / day.

[0079] The unit dose composition of the present invention preferably contains 10 mg to 5 g of urolithin, such as 20 mg to 2500 mg, such as 50 mg to 1500 mg, such as 250 mg to 1500 mg, such as 50 mg to 1000 mg, such as 50 mg to 250 mg, such as 250 mg to 1000 mg. The unit dose can be in the form of a snack bar: a snack bar weighing 25 to 150 g (such as 40 to 100 g) can contain the necessary amount of urolithin. The unit dose composition can alternatively be in the form of a beverage, for example, provided in a container (such as a sachet) suitable for a single dose volume (such as 100 to 300 ml). A beverage of 50 to 500 ml (such as 100 to 300 ml) can contain the necessary amount of urolithin. The beverage providing the composition of the present invention can contain urolithin at a concentration of 0.1 to 50 mg per ml (such as 0.5 to 10 mg per ml, such as 1 to 5 mg per ml).

[0080] The weight ratio between the protein component and urolithin is generally in the range of 1:10 to 5000:1, such as 1:10 to 1:1; such as 1:2.5 to 5000:1; such as 1:2.5 to 1200:1; such as 1:1 to 1200:1; such as 1:1 to 600:1; such as 2:1 to 5000:1; such as 2:1 to 12000:1; such as 3:1 to 5000:1; such as 3:1 to 1200:1; such as 3:1 to 1000:1; such as 3:1 to 500:1; such as 3:1 to 250:1; such as 5:1 to 1200:1; such as 5:1 to 600:1; such as 5:1 to 500:1; such as 5:1 to 400:1; such as 5:1 to 200:1; such as 5:1 to 100:1; such as 5:1 to 80:1; such as 5:1 to 50:1; such as 5:1 to 20:1, such as 6:1 to 15:1. Alternatively, the ratio can be, for example, 10:1 to 500:1, such as 10:1 to 100:1, such as 20:1 to 50:1, such as 30:1 to 40:1. In some embodiments, the ratio can be in the range of 50:1 to 5000:1; such as 70:1 to 2000:1, such as 100:1 to 500:1.

[0081] Urolithin generally constitutes 0.05 to 10% w / w of the composition of the present invention, 0.1 to 10% w / w of the composition of the present invention. For example, urolithin can constitute 0.2 - 8% w / w of the composition, such as 0.2 - 5% w / w of the composition, such as 0.3 - 3% / w of the composition, such as 0.5 - 2% / w of the composition. In some embodiments, urolithin can constitute 0.05 - 5% w / w of the composition, such as 0.1 - 2% w / w of the composition, such as 0.2 - 1% / w of the composition.

[0082] The composition of the present invention may thus contain from 5 to 80 g of protein and from 10 mg to 5 g of urolithin; for example, from 5 to 60 g of protein and from 10 mg to 5 g of urolithin; for example, from 5 to 40 g of protein and from 20 mg to 2500 mg; for example, from 5 to 40 g of protein and from 50 mg to 1000 mg of urolithin; for example, from 10 to 30 g of protein and from 50 mg to 1000 mg of urolithin; for example, from 10 to 30 g of protein and from 50 mg to 500 mg of urolithin; for example, from 10 to 30 g of protein and from 100 mg to 500 mg of urolithin. The composition preferably further contains carbohydrates, vitamins and minerals. Representative compositions are shown in Tables 1, 2 and 3:

[0083] Table 1: Representative powder compositions:

[0084] Composition Per 100 g Protein 10-80g Carbohydrate 20-40g Fat 0-20g Polyunsaturated fatty acid 0-5g Fiber 0-5g Vitamin 0 - 100% of each RDA Mineral 0 - 100% of each RDA Folic acid 0 - 1000 μg Niacin 0 - 100 mg Creatine 0-20g Urolithin A 0.025-5g

[0085] In bulk powder, the protein preferably constitutes 20% or more of the powder by weight, for example 20% or more by weight, for example 30% or more by weight, for example 40% or more by weight of the powder. For example, the protein may constitute 20 - 90% by weight of the powder, for example 30 - 80% by weight of the powder, for example 40 - 80% by weight of the powder, for example 40 - 70%, for example 60 - 80%, for example 60 - 70% by weight of the powder.

[0086] Bulk powder usually has instructions informing the individual how much powder to use per serving. For example, bulk powder may be supplied in a container with a spoon of the necessary size so that the correct amount of powder can be measured. The powder can be taken pure, mixed with food or added to water to make a drink.

[0087] Table 2: Representative beverage compositions:

[0088] Composition Per 100 mL Protein (e.g., 100% hydrolyzed whey) 5-15g Carbohydrate 1-20g Fat 0-9.5g Polyunsaturated fatty acid 0-2.5g Fiber 0-2g Vitamin 0 - 100% of each RDA Mineral 0 - 100% of each RDA Folic acid 0 - 500 μg Niacin 0 - 20 mg Urolithin A 10 - 2000 mg

[0089] Table 3: Representative bar compositions:

[0090] Composition Per bar 35 g Protein 6.7g Carbohydrate 10-20g Fat 0-15g Polyunsaturated fatty acid 2-6g Fiber 0-5g Niacin 0 - 100 mg Vitamin 0 - 100% of each RDA Mineral 0 - 100% of each RDA L - carnitine 0 - 500 mg Urolithin A 10 - 2000 mg

[0091] Table 4: Representative yogurt compositions:

[0092] Composition Per 100 g yogurt Protein 2-15g Carbohydrate 3-20g Fat 0-12g Calcium 5 - 20% RDA Fiber 0-4g Vitamin 0 - 100% of each RDA Mineral 0 - 100% of each RDA Live culture Streptococcus thermophilus, Lactobacillus bulgaricus, Lactobacillus acidophilus, Lactococcus lactis Urolithin A 10 - 2000 mg

[0093] The compositions of the present invention can be taken as a single treatment or more commonly as a series of treatments. In one example, an individual takes a dose before or after exercise. For individuals who are unable to exercise, for example, a dose of the composition can be taken once, twice, or three times a day or once, twice, three times, four times, five times, or six times a week. It should also be understood that the effective dose of the compound can be increased or decreased within a specific course of treatment.

[0094] Treatment:

[0095] The compositions of the present invention have been found to be useful for enhancing muscle performance, improving muscle function, preventing muscle function decline, increasing muscle mass, and / or reducing muscle wasting. Enhancing muscle performance, improving or maintaining muscle function, increasing muscle mass, and / or reducing muscle wasting can be part of a medical treatment, or it can be for personal preference ("lifestyle") or aesthetic reasons. The compositions of the present invention can be used as medicaments. The compositions can be used as dietary supplements, can be used as functional foods, functional beverages, or can be used as medical foods.

[0096] Most muscle enhancement programs require undergoing exercise and taking a muscle enhancement composition. There are indications that the combination of the protein and urolithin of the present invention is effective in promoting muscle growth, muscle strength, muscle endurance, and muscle function in the absence of exercise or with less necessary exercise.

[0097] The compositions have been found to be useful for treating diseases and disease states. The compositions have been found to be useful for managing the normal physiological functions of healthy individuals with conditions characterized by poor physical performance, impaired endurance, and impaired muscle function. The compositions of the present invention can improve the physical performance of individuals with diseases (including young and old individuals). The compositions of the present invention can improve physical performance, for example, of healthy individuals including athletes, non-athlete individuals, sedentary individuals, and the elderly, in terms of short-term or long-term performance. This improvement in performance can be measured by the time taken to walk or run a certain distance (e.g., improved performance during a 6-minute walk test (MWT)), increased time to run a certain distance, increased IPAQ score according to the International Physical Activity Questionnaire, increased number of chair-stands within a certain time, or another test designed to measure physical performance.

[0098] The compositions of the present invention further provide an increase in endurance. Endurance refers to the ability to perform at a constant workload (usually at <80% VO 2The time to fatigue when exercising at maximal intensity. The compositions of the present invention can increase the endurance of individuals with diseases, including young and old individuals. The compositions of the present invention can increase the endurance of healthy individuals, including athletes, non-athletic individuals, sedentary individuals, and the elderly. The present invention provides a method of prolonging the time to fatigue during a specific activity, such as fitness training, walking, running, swimming, or cycling. This increase in endurance can be evaluated using objective measurements, such as speed, oxygen consumption, or heart rate, or it can be a self-reported measurement, such as using a validated questionnaire.

[0099] The present invention further provides compositions to improve, maintain, or reduce loss of muscle function. The compositions of the present invention can improve, maintain, or reduce loss of muscle function in individuals with diseases, including young and old individuals. The compositions of the present invention can improve, maintain, or reduce loss of muscle function in healthy individuals, including athletes, non-athletic individuals, sedentary individuals, and the elderly. For example, the compositions of the present invention can improve, maintain, or reduce loss of muscle function in frail or pre-frail individuals. For example, the compositions of the present invention can increase muscle strength, as demonstrated by an increased ability to perform physical activities, such as exercise, for example, an increased ability to lift weights or an increased handgrip strength. In addition, the compositions of the present invention can improve muscle structure, for example, by increasing or maintaining muscle mass in the case of normal muscle function, declining muscle function, or impaired muscle function.

[0100] The present invention further provides compositions to improve physical performance or endurance, as perceived by an individual. For example, by reducing the perceived exertion or effort during exercise or as determined using a self-reported questionnaire.

[0101] Medical treatment:

[0102] The compositions of the present invention can be used as medicaments. The compositions of the present invention are found to be useful for treating muscle-related pathological conditions. Accordingly, the present invention provides the compositions of the present invention for treating muscle-related pathological conditions. The present invention also provides a method of treating a muscle-related pathological condition in an individual, the method comprising administering to the individual an effective amount of the composition of the present invention. Muscle-related pathological conditions include conditions that commonly affect healthy individuals as well as pathological conditions. Such muscle conditions are found in healthy individuals or in individuals affected by diseases including: musculoskeletal diseases or disorders; cachexia; muscle wasting; myopathy; age-related muscle function decline; pre-frailty; frailty; neuromuscular diseases, such as Duchenne muscular dystrophy and other dystrophies; sarcopenia, for example, acute sarcopenia; muscle atrophy and / or cachexia, for example, associated with burns, bed rest, limb immobilization, or thoracic, abdominal, and / or orthopedic surgery; and muscle degenerative diseases.

[0103] Examples of age-related disease conditions treatable with the compositions of the present invention include sarcopenia and muscle wasting.

[0104] It has been reported in WO2014 / 111580 that urolithin B (but not urolithin A) increases the average diameter of in vitro myotubes. No effect with urolithin A was found.

[0105] Muscle performance:

[0106] The compositions of the present invention are suitable for improving muscle performance. The present invention thus provides the compositions of the present invention for improving muscle performance. The present invention also provides a method for improving muscle performance by administering to an individual an effective amount of the compositions of the present invention. The administration can be self-administration.

[0107] Improved muscle performance can be one or more of improved muscle function, reduced decline in muscle function, increased muscle strength, increased muscle endurance, and increased muscle recovery.

[0108] The compositions of the present invention can thus be used in a method for improving physical endurance (e.g., the ability to perform physical tasks such as exercise, physical labor, sports activities), suppressing or delaying physical fatigue, increasing work capacity and endurance, and reducing muscle fatigue.

[0109] Improved muscle function can be particularly beneficial in elderly individuals with reduced muscle function due to age-related conditions. For example, individuals who can benefit from improved muscle function may experience a decline in muscle function, which subsequently leads to pre-frailty and frailty. Such individuals may not necessarily experience muscle wasting in addition to their decline in muscle function. Some individuals do experience muscle wasting and decline in muscle function, such as individuals with sarcopenia. By administering the compositions of the present invention to frail or pre-frail individuals, the compositions of the present invention can be used to improve muscle performance.

[0110] Muscle performance can be sports performance, that is, the muscle ability of an athlete when participating in sports activities. Improved sports performance, strength, speed, and endurance are measured by an increase in muscle contraction intensity, an increase in muscle contraction amplitude, or a shortening of the muscle reaction time between stimulation and contraction. An athlete is an individual who participates in sports to any degree and attempts to obtain an improved degree of intensity, speed, or endurance during their performance, e.g., bodybuilders, cyclists, long-distance runners, and short-distance runners. Improved sports performance is demonstrated by the ability to resolve muscle fatigue, maintain activity for a longer period of time, and have a more effective workout.

[0111] Examples

[0112] The following examples illustrate the present invention.

[0113] Compound

[0114] Urolithin A was prepared as follows:

[0115] Urolithin A (4) was prepared in two steps starting from bromide 1 and resorcinol 2. The pure compound was obtained as a pale yellow powder.

[0116]

[0117] Step 1:

[0118] A mixture of 2-bromo-5-methoxybenzoic acid 1 (27.6 g; 119 mmol; 1.0 eq), resorcinol 2 (26.3 g; 239 mmol; 2.0 eq) and sodium hydroxide (10.5 g; 263 mmol; 2.2 eq) in water (120 mL) was heated under reflux for 1 h. Subsequently, 5% aqueous copper sulfate solution (3.88 g CuSO 4 ·5H 2 O in 50 mL of water; 15.5 mmol; 0.1 eq) was added and the mixture was refluxed for an additional 30 min. The mixture was cooled to room temperature and the solid was filtered on a Büchner filter. The residue was washed with cold water to give a light red solid, which was triturated in hot MeOH. The suspension was left standing overnight at 4 °C. The resulting precipitate was filtered and washed with cold MeOH to give the title compound 3 as a light brown solid.

[0119] Step 2:

[0120] At 0 °C, a 1 M solution of boron tribromide in anhydrous dichloromethane (11.93 mL of pure BBr 3 in 110 mL of anhydrous dichloromethane; 124 mmol; 3.0 eq) was added dropwise to a suspension of 3 (10.0 g; 41 mmol; 1.0 eq) in anhydrous dichloromethane (100 mL). The mixture was left standing at 0 °C for 1 h and then allowed to warm to room temperature. The solution was stirred at this temperature for 17 h. Subsequently, ice was added to the mixture in excess. The yellow precipitate was filtered and washed with cold water to give a yellow solid, which was heated to reflux in acetic acid for 3 h. The hot solution was filtered rapidly and the precipitate was washed successively with acetic acid and ether to give the title compound 4 as a yellow solid. 1 H and 13 C NMR were consistent with the structure of 4.

[0121] Example 1: Experimental trial on muscle function with or without urolithin A supplementation with optimal protein

[0122] a) Optimal protein diet containing urolithin A

[0123] To simulate age-related muscle loss in humans, an experimental animal model was established in aged mice. The control diet designed for experimental studies was a high-protein diet, which would be similar to the clinically recommended high-protein diet in the elderly at risk of muscle loss. The diet was formulated to improve the performance of the aged animals that consumed them. The high-protein diet had a better balance of essential nutrients (amino acids, vitamins, and minerals) and was supplemented with 200 gr of casein per kilogram of diet, compared to 140 gr of casein in the conventional maintenance diet (Reeves PG, J. Nutr. 1997, 127(5) 838S-841S). Casein protein is a nutritionally complete and highly digestible protein with a high amino score, which contains all amino acids in amounts sufficient to support the maintenance of all human proteins. The composition of the experimental high-protein diet is shown in Table 5 below. Urolithin A was mixed with the high-protein diet at a content of 0.57 g per kilogram of diet. The two diets were isocaloric.

[0124] Table 5: Composition of the feed:

[0125]

[0126]

[0127] b) The protein in combination with urolithin A in the diet was better compared to the protein of only 22-month-old C57BL / 6J aged mice, which would be equivalent to the elderly aged 65 to 75 years, treated with only the high-protein diet or the high-protein diet containing urolithin A. In addition to casein protein, both diets contained essential nutrients for optimal muscle function, such as L-cysteine and a mixture of vitamins and minerals. The content of urolithin A in the diet resulted in a dose delivery of 50 mg / kg / day to the mice.

[0128] The endurance of the mice was tested on a treadmill before and after 6 weeks of treatment with a combination of urolithin A and protein. The endurance test was conducted during the day. The mice were given food and water before and after exercise. The test was performed using a treadmill (Panlab, Barcelona, Spain) placed in front of an electrified grid. The mice were acclimated to the treadmill set at 0.3 mA for 5 minutes. The exercise started with a running speed of 15 cm / sec for 12 minutes. Subsequently, the speed was increased by 3 cm / sec every 12 minutes. The animal was removed from the treadmill when it touched the rear grid more than 5 times per minute for two consecutive minutes. After 6 weeks of treatment, the total distance and running time were normalized to the baseline value. None of the groups of mice underwent an exercise protocol before the endurance test. The mice were maintained in a standard animal housing environment throughout the study.

[0129] The test results are shown in Figure 1In. Surprisingly, it was observed that mice fed with urolithin A in addition to a high-protein diet showed an increase in running distance of 42% and running time of 28% compared to mice receiving only a protein diet. This improvement in running endurance occurred in the absence of an exercise program. Statistical significance was determined using a Fisher's t-test. ***: p < 0.001.

[0130] These results suggest the ability of urolithin A in combination with an optimal protein diet to enhance muscle function in aging animals. Similar improvements are expected to be observed in the elderly in the presence of urolithin A, where, as current medical standards, it is recommended to use only an optimal protein diet.

[0131] Example 2: Powder chemical formula composition targeting healthy aging and age-related muscle loss containing high protein and urolithin A

[0132] Table 6:

[0133]

[0134]

[0135] The composition with the nutrient profile shown in Table 6 is given to individuals to counter age-related muscle loss.

[0136] Example 3: Enteral nutrition liquid composition targeting immobilized individuals in intensive care or hospital settings containing protein and urolithin A

[0137] Table 7:

[0138]

[0139]

[0140] The beverage composition with the nutrient profile shown in Table 7 is given to immobilized individuals in intensive care or hospital settings.

[0141] Example 4: Cereal bar composition targeting active athletes with optimal muscle function during endurance training containing protein and urolithin A

[0142] Table 8:

[0143] Composition Per bar 35 g Energy 600 kcal Protein 6.7g Carbohydrate 17.2g Fat 7.6g Polyunsaturated fatty acid 3.8g Fiber 1.6g Niacin 25 mg Zinc 2.5 mg Calcium 180 mg Sodium 25 mg Potassium 60 mg Magnesium 80 mg L - carnitine 200 mg Urolithin A 250 mg

[0144] The bar composition with the nutrient profile shown in Table 8 is given to active athletes with optimal muscle function during endurance.

[0145] Example 5: Yogurt composition

[0146] Table 9:

[0147] Nutritional value: Per 100 g Fat 0,2g Carbohydrate 3,7g Protein 9,8g Vitamin B2 0.18 mg 13% of RDA Calcium 95 mg 12% of RDA Phosphorus 170 mg 24% of RDA Live active culture Urolithin A 250 mg, 500 mg or 1000 mg

[0148] Example 6: Example 3: Influence of Particle Size on the Bioavailability of Urolithin A

[0149] The particle size of urolithin A was reduced in a controlled manner using an MC50 Spiral Jetmill, filtered nitrogen, a feed rate of 240 g / hr, a Venturi pressure of 12 bar and a mill pressure of 12 bar. The different particle size distributions of urolithin A were determined on a Malvern particle size analyzer (Malvern Instruments, UK). The depth of three samples was evaluated. The particle size distribution D 10 of Sample #1 of urolithin A was 1.03 μm, D 50 was 53.4 μm and D 90 was 365 μm. The particle size D 10 of Sample #2 of urolithin A was 0.272 μm, D 50 was 2.17 μm and D 90 was 6.84 μm. The particle size distribution D 10 of Sample #3 of urolithin A was 0.597 μm, D 50 was 5.67 μm and D 90 was 40.1 μm.

[0150] Table 10: Particle Size Determination of Urolithin A before and after Micronization

[0151] Urolithin A <![CDATA[D 10 > <![CDATA[D 50 > <![CDATA[D 90 > Sample #1 1.03 μm 53.4 μm 365 μm Sample #2 0.272 μm 2.17 μm 6.84 μm Sample #3 0.597 μm 5.67 μm 40.1 μm

[0152] To demonstrate the influence of a specific particle size distribution on bioavailability, male Sprague-Dawley rats were fasted overnight and then administered, by oral gavage, Sample #1, Sample #2 or Sample #3 of urolithin A suspended in 15% DMSO, 85% (0.5% methylcellulose, 0.25% Tween 80 in water) at a dose corresponding to 25 mg / kg / day.

[0153] Table 11: Design of the Bioavailability Study.

[0154]

[0155] The solution for gavage was prepared as follows: 35 mg of urolithin A powder was diluted in 7 ml of 15% DMSO, 0.5% methylcellulose / 0.25% Tween 80 in water to produce a 5 mg / ml fine suspension. DMSO was obtained from BDH, methylcellulose was obtained from Sigma, and Tween 80 was obtained from Sigma-Aldrich.

[0156] Blood was collected from rats via jugular vein cannulation at different time points, and urolithin A was quantified in plasma after oral gavage of sample #1, sample #2, and sample #3 to determine its pharmacokinetic profile. The study was repeated on three rats for each sample. Figure 2 The resulting pharmacokinetic profiles of urolithin A samples #1 and #2 are shown. The data collected are summarized in Table 12 below.

[0157] Table 12: Results of bioavailability studies of urolithin A with different particle sizes

[0158]

[0159] When the particle size was reduced to below 50 μm D 90 urolithin A showed an increase in bioavailability. For sample #2, compared to sample #1, there was a 116% relative increase in C 最大 (a 2.16-fold increase) and a 28% increase in AUC. For sample #3, there was a 26% relative increase in AUC.

[0160] These results demonstrate that, when compared to the preparation of urolithin A with a particle size of D 90 > 300 μm, the preparation of urolithin A with a particle size of D 90 < 50 μm consistently showed higher bioavailability. In addition, the preparation of urolithin A with a particle size of D 90 < 20 μm was found to be particularly beneficial and a significantly higher peak urolithin A blood level was obtained as more than twice that of the C 最大 .

Claims

1. A composition, comprising: a) a protein source and b) a compound of formula (I) or a salt thereof: Wherein: A, B, C and D are each independently selected from H and OH; W, X and Y are each independently selected from H and OH; and Z is selected from H and OH.

2. The composition according to claim 1, wherein the compound of formula (I) is urolithin A.

3. The composition according to claim 1 or claim 2, wherein D of the compound of formula (I) 50 has a size in the range of 0.5 to 50 μm, and D 90 has a size in the range of 5 to 100 μm.

4. The composition according to any one of the preceding claims, wherein the protein constitutes 20 - 99% w / w of the composition.

5. The composition according to claim 4, wherein the protein constitutes 30 - 80% w / w of the composition.

6. The composition according to any one of claims 1 to 5, wherein the weight ratio between the protein component and the urolithin is in the range of 2:1 to 5000:

1.

7. The composition according to any one of claims 1 to 6, wherein the protein is a hydrolyzed, partially hydrolyzed or non - hydrolyzed protein.

8. The composition according to claim 7, wherein the protein is derived from a source selected from: milk (e.g., casein, whey), animal (e.g., meat, fish), cereal (e.g., rice, corn) or plant (e.g., soybean, pea) sources.

9. The composition according to claim 8, wherein the protein is selected from intact pea protein, intact pea protein isolate, intact pea protein concentrate, milk protein isolate, milk protein concentrate, casein protein isolate, casein protein concentrate, whey protein concentrate, whey protein isolate, sodium caseinate or calcium caseinate, whole milk, partially or fully skimmed milk, soy protein isolate and soy protein concentrate, and combinations thereof.

10. The composition according to any one of claims 1 to 9, wherein the composition is in the form of a yogurt.

11. The composition according to any one of claims 1 to 9, wherein the composition is in the form of a solid (e.g., tablets or sticks), semi - solid (e.g., soft gels, capsules (e.g., hard capsules) or pills), powder or liquid (including emulsions).

12. The composition according to any one of claims 1 to 11, the composition is used as a medicament, dietary supplement, functional food, functional beverage or medical food.

13. The composition according to claim 12, the composition is used as a medicament.

14. The composition according to claim 13, the composition is used as a medicament for treating muscle - related pathological conditions.

15. A method for treating muscle - related pathological conditions, the method comprising administering to an individual in need a composition according to any one of claims 1 to 11.

16. The composition used according to claim 14 or the method according to claim 15, wherein the muscle-related pathological condition is selected from muscle skeletal diseases or disorders; muscle wasting; myopathy; neuromuscular diseases, such as Duchenne muscular dystrophy and other dystrophic sarcopenia, such as acute sarcopenia; and muscle atrophy and / or cachexia, such as muscle atrophy and / or cachexia associated with burns, bed rest, limb immobilization or thoracic, abdominal and / or orthopedic surgery.

17. A method for improving muscle performance, the method comprising administering to an individual an effective amount of the composition according to any one of claims 1 to 11.

18. The method for improving muscle performance according to claim 17, wherein the individual suffers from age-related muscle function decline, age-related sarcopenia, age-related muscle wasting, physical fatigue, muscle fatigue, and / or is frail or pre-frail.

19. The method according to claim 18, wherein the individual is frail or pre-frail.

20. A method for treating a muscle-related pathological condition of an individual or improving the muscle function of an individual, the method comprising administering to the individual an effective amount of urolithin (such as urolithin A) and an effective amount of protein, the administration being carried out simultaneously or at separate time intervals.

21. A kit for use in the method according to claim 20, the kit comprising urolithin (such as urolithin A) and protein.

22. A compound of formula (I) or a salt thereof, wherein: A, B, C and D are each independently selected from H and OH; W, X and Y are each independently selected from H and OH; and Z is selected from H and OH, And wherein the D of the compound or salt 50 size ranges from 0.5 to 50 μm, and D 90 size ranges from 5 to 100 μm.

23. The compound or salt according to claim 22, wherein D of the compound 90 has a size in the range of 8.2 to 16.0 μm, D 50 has a size in the range of 2.8 to 5.5 μm, and D 10 has a size in the range of 0.5 to 1.0 μm.

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