CROSS-REFERENCE TO RELATED APPLICATIONS

[001] This application claims priority to and any benefit of U.S. Provisional Application

No. 62/050,919, filed September 16, 2014, the content of which is incorporated herein by reference in its entirety.

FIELD OF THE DISCLOSURE

[002] The present disclosure relates to methods of preserving muscle strength in a subject during a period of muscle disuse. Particularly, the present disclosure relates to the use of compositions comprising B-hydroxy-B-methylbutyrate and green tea extract to preserve muscle strength in such subjects during a period of muscle disuse and, optionally, during a period of muscle recovery.

BACKGROUND

[003] Prolonged muscle disuse can lead to loss of muscle tissue and reduced muscle strength. Muscle disuse can be due to immobilization (e.g., casting), injury, disease, bed rest, hospitalization, extended air travel, weightlessness, and the like. The loss of muscle tissue and muscle strength is generally exacerbated by aging. This loss of muscle tissue and muscle strength may impair a subject's mobility, which discourages physical activity and leads to even further loss of muscle tissue. Hence, a relatively short period of muscle disuse may begin a downward spiral of muscle loss, increased dependence, and lowered quality of life.

[004] Conventionally, exercise during the recovery period after muscle disuse has been the primary intervention to rebuild muscle tissue and muscle strength. However, exercise may not always be feasible, especially if the subject is elderly, recovering from serious illness, or has been immobilized for an extended period of time. Therefore, nutritional interventions that can prevent or slow the loss of muscle strength during the period of muscle disuse can be highly desirable.

SUMMARY

[005] Disclosed herein are methods of preserving muscle strength of a subject during a period of muscle disuse. Muscle strength is preserved by administering a composition containing B-hydroxy-B-methylbutyrate (HMB) and green tea extract (GTE) to the subject.

[006] In certain embodiments, methods of preserving muscle strength of a subject during a period of muscle disuse are disclosed. In certain embodiments, the period of muscle disuse is at least about 4 hours. In some embodiments, the period of muscle disuse is from about 24 hours to about 36 months. In some embodiments, the methods include administering a composition comprising an effective amount of HMB and an effective amount of GTE to the subject during at least a portion of the period of muscle disuse.

[007] This embodiment includes a composition for use in preserving muscle strength of a subject during a period of muscle disuse, wherein the composition comprises an effective amount of green tea extract, and an effective amount of B-hydroxy-B-methylbutyrate and where the composition is administered during at least a portion of the period of muscle disuse, and the period of muscle disuse is at least 4 hours.

[008] This embodiment also includes use of a composition comprising an effective amount of green tea extract and an effective amount of B-hydroxy-B-methylbutyrate for the manufacture of a medicament for preserving muscle strength of a subject during a period of muscle disuse wherein the composition is administered during at least a portion of the period of muscle disuse and the period of muscle disuse is at least 4 hours.

[009] In certain embodiments, methods of preserving muscle strength of a subject during a period of muscle disuse and a subsequent period of muscle recovery are disclosed. The period of muscle disuse and the period of muscle recovery are each at least about 4 hours. In some embodiments, the methods include administering a composition comprising an effective amount of HMB and an effective amount of GTE to the subject during at least a portion of both the period of muscle disuse and the period of muscle recovery.

[010] This embodiment also includes a composition for use in preserving muscle strength of a subject during a period of muscle disuse and a period of muscle recovery following the period of muscle disuse, wherein the composition comprises an effective amount of green tea extract, and an effective amount of B-hydroxy-B-methylbutyrate and where the composition is administered during at least a portion of the period of muscle disuse and at least a portion of the muscle recovery following the period of muscle disuse, and the period of muscle disuse and the period of muscle recovery are each at least 4 hours.

[Oi l] This embodiment also includes use of a composition comprising an effective amount of green tea extract and an effective amount of B-hydroxy-B-methylbutyrate for the manufacture of a medicament for preserving muscle strength of a subject during a period of muscle disuse and a period of muscle recovery following the period of muscle disuse wherein the composition is administered during at least a portion of the period of muscle disuse and at least a portion of the muscle recovery following the period of muscle disuse and the period of muscle disuse and the period of muscle recovery are each at least 4 hours.

[012] In certain embodiments, methods of preserving muscle strength of a subject during a period of muscle disuse are disclosed. The period of muscle disuse is at least about 4 hours. In some embodiments, the methods include administering a composition comprising an effective amount of leucine or a leucine metabolite and an effective amount of GTE to the subject during at least a portion of the period of muscle disuse.

[013] This embodiment also includes a composition for use in preserving muscle strength of a subject during a period of muscle disuse, wherein the composition comprises an effective amount of green tea extract, and an effective amount of leucine or a leucine metabolite, and where the composition is administered during at least a portion of the period of muscle disuse, and the period of muscle disuse is at least 4 hours.

[014] This embodiment also includes use of a composition comprising an effective amount of green tea extract and an effective amount of leucine or a leucine metabolite for the manufacture of a medicament for preserving muscle strength of a subject during a period of muscle disuse wherein the composition is administered during at least a portion of the period of muscle disuse and the period of muscle disuse is at least 4 hours.

[015] In certain embodiments, methods of preserving muscle strength of a subject during a period of muscle disuse and a subsequent period of muscle recovery are disclosed. The period of muscle disuse and the period of muscle recovery are each at least about 4 hours. In some embodiments, the methods include administering a composition comprising an effective amount of leucine or a leucine metabolite and an effective amount of GTE to the subject during at least a portion of both the period of muscle disuse and the period of muscle recovery.

[016] This embodiment also includes a composition for use in preserving muscle strength of a subject during a period of muscle disuse and a period of muscle recovery following the period of muscle disuse, wherein the composition comprises an effective amount of green tea extract, and an effective amount of leucine or a leucine metabolite, and where the composition is administered during at least a portion of the period of muscle disuse and at least a portion of the muscle recovery following the period of muscle disuse, and the period of muscle disuse and the period of muscle recovery are each at least 4 hours.

[017] This embodiment also includes use of a composition comprising an effective amount of green tea extract and an effective amount of leucine or a leucine metabolite for the manufacture of a medicament for preserving muscle strength of a subject during a period of muscle disuse and a period of muscle recovery following the period of muscle disuse wherein the composition is administered during at least a portion of the period of muscle disuse and at least a portion of muscle recovery following the period of muscle disuse and the period of muscle disuse and the period of muscle recovery are each at least 4 hours. BRIEF DESCRIPTION OF THE DRAWING

[018] FIGURE 1 illustrates muscle strength performance of non-immobilized limbs of rats after the rats consumed compositions comprising HMB, GTE, neither, or both.

[019] FIGURE 2 illustrates muscle strength performance of immobilized limbs of rats after the rats consumed compositions comprising HMB, GTE, neither, or both.

DETAILED DESCRIPTION

[020] While embodiments encompassing the general inventive concepts may take diverse forms, various embodiments will be described herein, with the understanding that the present disclosure is to be considered merely exemplary, and the general inventive concepts are not intended to be limited to the disclosed embodiments.

[021] Methods of preserving muscle strength of a subject during a period of muscle disuse are disclosed herein. Muscle strength is preserved by administering a composition comprising an effective amount of HMB and GTE to the subject. In particular, the methods comprise administering at least one serving per day of a composition comprising from about 0.1 to about 10 g HMB and from about 20 mg to about 2,000 mg GTE per serving to the subject. It has been unexpectedly found that administering compositions containing HMB and GTE is more effective at preserving muscle strength than administering compositions containing either ingredient alone.

[022] In certain embodiments, methods of preserving muscle strength of a subject during a period of muscle disuse are disclosed. In some embodiments, the period of muscle disuse is at least 4 hours. In some embodiments, the period of muscle disuse is from about 24 hours to about 36 months. The methods include administering a composition comprising an effective amount of HMB and an effective amount of GTE to the subject during at least a portion of the period of muscle disuse.

[023] In certain embodiments, methods of preserving muscle strength of a subject during a period of muscle disuse and a subsequent period of muscle recovery are also disclosed. Muscle strength is preserved by administering a composition comprising an effective amount of HMB and an effective amount of GTE to the subject during at least a portion of both the period of muscle disuse and the period of muscle recovery. The period of muscle disuse and the period of muscle recovery are each at least about 4 hours.

[024] Methods of preserving muscle strength of a subject during a period of muscle disuse are also disclosed. Muscle strength is preserved by administering a composition comprising an effective amount of leucine or a leucine metabolite (other than HMB) and an effective amount of GTE to the subject. Exemplary leucine metabolites include but are not limited to a-ketoisocaproic acid, a-hydroxyisocaproic acid, or a combination thereof.

[025] In certain embodiments, methods of preserving muscle strength of a subject during a period of muscle disuse are disclosed. The period of muscle disuse is at least 4 hours. The methods include administering a composition comprising an effective amount of leucine or a leucine metabolite and an effective amount of GTE to the subject during at least a portion of the period of muscle disuse.

[026] In certain embodiments, methods of preserving muscle strength of a subject during a period of muscle disuse and a subsequent period of muscle recovery are disclosed. The period of muscle disuse and the period of muscle recovery are each at least 4 hours. The methods include administering a composition comprising an effective amount of leucine or a leucine metabolite and an effective amount of GTE to the subject during at least a portion of both the period of muscle disuse and the period of muscle recovery.

[027] The terms "administering" or "being administered" as used herein, unless otherwise specified, should be understood to comprise at least one of: a) providing the composition to a subject; and b) the act of consuming the composition. Unless otherwise indicated, the composition is administered to the subject orally or enterally.

[028] The term "muscle disuse" as used herein, unless otherwise specified, refers to a substantial lack of activity of a particular muscle, muscle type, or muscle group due to partial or full immobilization, casting, injury, illness, bed rest, hospitalization, extended air travel (e.g., flights that are at least 4 hours in duration), weightlessness, and the like. [029] The term "muscle recovery" as used herein, unless otherwise specified, refers to use of a particular muscle, muscle type, or muscle group, after a period of muscle disuse. Muscle recovery may include gentle stretching, contraction, and movement of the muscles (e.g., walking around the house) and structured rehabilitation after the muscles have been inactive. Muscle recovery may, but does not necessarily, include strenuous exercise, including weight- bearing, resistance, and cardiovascular exercise, to quickly rebuild and increase muscle mass and muscle strength.

[030] The term "nutritional composition" as used herein, unless otherwise specified, refers to nutritional products in various forms including, but not limited to, liquids, solids, powders, semi-solids, semi-liquids, nutritional supplements, and any other nutritional food product known in the art. As discussed below, in certain embodiments, the nutritional compositions comprise at least one of a source of protein, a source of carbohydrate, and a source of fat.

[031] The terms "nutritional liquid" or "liquid nutritional composition" as used herein, unless otherwise specified, are used interchangeably to refer to nutritional compositions in ready- to-drink liquid form, e.g., liquid nutritional products; concentrated liquid form; and nutritional liquids made by reconstituting nutritional powders as described herein prior to use. The liquid nutritional composition may be formulated as a suspension, an emulsion, a solution, and the like.

[032] The terms "nutritional powder" or "powdered nutritional composition" as used herein, unless otherwise specified, are used interchangeably to refer to nutritional compositions in a solid flowable or scoopable form, and includes spray-dried powders, extruded, dry-mixed, or dry-blended powders, and the like. A nutritional powder may be reconstituted upon addition of water or another liquid to form a liquid nutritional composition prior to being administered to a subject.

[033] The term "nutritional semi-liquid" as used herein, unless otherwise specified, refers to nutritional compositions that are intermediate in properties, such as flow properties, between liquids and solids. Some semi-liquid examples include thick shakes, liquid yogurts, liquid gels, and the like. [034] The term "nutritional semi-solid" as used herein, unless otherwise specified, refers to nutritional products that are intermediate in properties, such as rigidity, between solids and liquids. Some semi-solid examples include puddings, yogurts, gels, gelatins, doughs, and the like.

[035] The term "period" as used herein, unless otherwise specified, refers to a continuous interval of time. A period may be about 4 hours, about 8 hours, about 12 hours, about 24 hours, about 48 hours, about 72 hours, about one week, about two weeks, about one month, about two months, about three months, about six months, about nine months, about twelve months, or longer than twelve months in duration.

[036] The term "period of muscle disuse" refers to the interval of time that the muscle or muscles are substantially inactive. For the purpose of this disclosure, a period of muscle disuse is at least 4 hours of substantially continuous muscle inactivity. However, it should be understood that occasional short intervals of mild muscle use, such as sitting up in bed or moving from bed to toilet, may be included within a period of muscle disuse.

[037] The term "period of muscle recovery" refers to the interval of time that the muscle or muscles are active, for the purpose of regaining at least some muscle mass and strength after a period of muscle disuse. The period of muscle recovery will typically closely follow in time a period of muscle disuse. For the purpose of this disclosure, a period of muscle recovery is at least 4 hours of intermittent sessions of deliberate muscle activity, which may include intervals of rest and sleep between the sessions of muscle activity. In other words, it should be understood that, for example, a "24 hour period of muscle recovery" does not necessarily refer to 24 hours of continuous muscle activity without rest.

[038] The term "serving," as used herein, unless otherwise specified, refers to an amount of nutritional composition that is intended for consumption or otherwise consumed in one sitting, which may last up to one or up to two hours.

[039] The term "solid nutritional composition" as used herein, unless otherwise specified, refers to nutritional products that are in solid form. Some examples of solid nutritional products include: bars; sticks; cookies, breads, cakes, or other baked good; frozen liquids; candy; breakfast cereals; snack chips or bites; frozen or retorted entrees; and the like.

[040] The term "subject" as used herein, unless otherwise specified, refers to an animal, including but not limited to, a human, a domesticated farm animal (e.g., cow, horse, pig, or chicken), or a pet (e.g., dog or cat). In certain embodiments, the subject is a human. fi-Hvdroxy-fi-Methylbutyrate (HMB)

[041] The compositions of the present disclosure comprise HMB. Any source of HMB is suitable for use herein. Suitable sources of HMB include HMB as a free acid, a salt, an anhydrous salt, an ester, a lactone, or other product forms that otherwise provide a bioavailable form of HMB in the composition. Non-limiting examples of suitable salts of HMB for use herein include sodium, potassium, calcium, magnesium, chromium, or other non-toxic HMB salts. Suitable HMB salts may be in anhydrous or hydrated forms. Calcium HMB monohydrate is a preferred source of HMB, and is commercially available from, for example, Technical Sourcing International (TSI), Missoula, Montana.

[042] When the composition is a liquid, the effective concentration of HMB in the liquid may be up to about 10%, including from about 0.01% to about 10%>, including from about 0.1%o to about 10%), including from about 0.1 % to about 5%, including from about 0.1 % to about 3%o, including from about 0.1 % to about 2%, including from about 0.1% to about 1.5%, including from about 0.1 % to about 1%, including from about 0.3% to about 10%, including from about 0.5% to about 10%, including from about 0.7% to about 10%, including from about P/o to about 10%), including from about 2% to about 10%, including from about 3% to about 10%), and including from about 5% to about 10% by weight of the liquid.

[043] When the composition is a solid, the effective concentration of HMB in the solid may be up to about 10%, including from about 0.1% to about 10%, including from about 0.1% to about 7%o, including from about 0.1% to about 5%, including from about 0.1% to about 3%, including from about 0.1% to about 2%, including from about 0.1% to about 1.5%, including from about 0.1% to about 1.0%, including from about 0.3% to about 10%, including from about 0.5%) to about 10%), including from about 1% to about 10%, including from about 2% to about 10%, including from about 3% to about 10%, including from about 4% to about 10%>, including from about 5% to about 10%>, and including from about 7% to about 10%> by weight of the solid.

[044] The compositions may provide from about 0.1 g/day to about 10 g/day of HMB in accordance with the methods described herein, including from about 0.1 g/day to about 5 g/day, including from about 0.1 g/day to about 3 g/day, including from about 0.1 g/day to about 2 g/day, including from about 0.1 g/day to about 1.5 g/day, including from about 0.1 g/day to about 1 g/day, including from about 0.3 g/day to about 10 g/day, including from about 0.3 g/day to about 5 g/day, including from about 0.3 g/day to about 3 g/day, including from about 0.3 g/day to about 1 g/day, including from about 0.5 to about 10 g/day, including from about 0.5 g/day to about 5 g/day, including from about 0.5 g/day to about 3 g/day, including from about 0.75 g/day to about 10 g/day, including from about 0.75 g/day to about 5 g/day, including from about 0.75 g/day to about 3 g/day, including from about 1 g/day to about 10 g/day, including from about 1 g/day to about 5 g/day, and including from about 1 g/day to about 3 g/day of HMB.

Leucine and Other Leucine Metabolites

[045] The compositions of the present disclosure may comprise leucine or other metabolites of leucine instead of HMB. Like the compositions comprising HMB and GTE, compositions comprising leucine or other metabolites of leucine and GTE may enhance the preservation of muscle strength in subjects during periods of muscle disuse.

[046] For example, a-hydroxyisocaproic acid (HICA), also known as leucic acid or 2- hydroxy-4-methylvaleric acid, is an end product of leucine metabolism in human tissues. One particularly useful form of HICA for use in the methods and compositions disclosed herein is the calcium salt of HICA, which may include the anhydrous monohydrate thereof. The HICA used in the compositions of the present disclosure can come from any source, and, in certain embodiments, the HICA is L-2-hydroxy-4-methylvaleric acid. HICA is commercially available from, for example, Ark Pharm Inc., Libertyville, Illinois or TCI America, Portland, Oregon.

[047] In certain embodiments, the amount of HICA in the compositions is from about

0.15 g/serving to 2.5 g/serving of the composition. In other embodiments, the amount of HICA is from about 0.5 g/serving to about 2 g/serving, including from about 1 g/serving to 1.5 g/serving. In certain embodiments, the amount of HICA administered per day includes from about 0.15 g/day to about 10 g/day of HICA, including from about 0.5 g/day to about 7 g/day, including from about 1 g/day to about 5 g/day of HICA. A subject may be administered one serving per day, two servings per day, three servings per day, or four or more servings per day to receive the desired amount of HICA.

[048] Another exemplary metabolite of leucine is a-ketoisocaproic acid (KIC), also known as ketoleucine or 4-methyl-2-oxopentanoic acid. KIC is an intermediate product of leucine metabolism in human tissues. One particularly useful form of KIC for use in the methods and compositions disclosed herein is the calcium salt of KIC, which may include the anhydrous monohydrate thereof. The KIC used in the compositions of the present disclosure can come from any source, and is commercially available from, for example, TCI America, Portland, Oregon or Finetech Industry Ltd, London, UK.

[049] In certain embodiments, the amount of KIC in the compositions is from about

0.15 g/serving to 5 g/serving of the composition. In other embodiments, the amount of KIC is from about 0.3 g/serving to 3 g/serving, including from about 0.5 g/serving to 1.5 g/serving. In certain embodiments, the amount of KIC administered per day includes from about 0.15 g/day to 10 g/day of KIC, including from about 0.3 g/day to about 7 g/day, including from about 0.5 g/day to 5 g/day of KIC. A subject may be administered one serving per day, two servings per day, three servings per day, or four or more servings per day to receive the desired amount of KIC.

Green Tea Extract (GTE)

[050] The compositions of the present disclosure comprise GTE. The GTE disclosed herein is derived from green tea leaves. GTE comprises a polyphenol, epigallocatechin gallate ("EGCg"), either alone or in combination with other polyphenol compounds, which is isolated from green tea as an extract. The GTE may be in the form of a liquid, a solid (e.g., a powder), and mixtures thereof. GTE is commercially available from, for example, Taiyo International, Inc., Minneapolis, Minnesota.

[051] In addition to containing EGCg, suitable green tea extracts used with the compositions disclosed herein may contain other polyphenols including but not limited to, other catechins such as catechin (i.e., (+)-catechin, also known as "C"), epicatechin ("EC"), gallocatechin ("GC"), epigallocatechin ("EGC"), and epicatechin gallate ("ECg"); flavones such as apigenin, isoviloxin, sapotarin, and vicenin-2; flavonols such as kaempherol, quercetin, and myricetin; condensed flavonoids; and tannin glycosides. Accordingly, in certain embodiments, in addition to the EGCg, the green tea extracts disclosed herein include at least one of C, EC, GC, EGC, ECg, and combinations thereof. In certain embodiments, the GTE may contain caffeine, contain a trace amount of caffeine, or may be substantially free of caffeine (i.e., decaffeinated).

[052] In certain embodiments disclosed herein, the green tea extract contains about 20% by solid weight of EGCg, including about 25%, about 30%>, about 40%>, about 50%>, about 70%>, about 80%), about 90%>, and about 100% by solid weight of EGCg. In accordance with certain of the preceding embodiments, the green tea extract contains from about 20% to 100% by solid weight of EGCg, including from about 25% to 100%, about 30% to 100%, about 40% to 100%, about 50% to 100%, about 70% to 100%, about 80% to 100%, and about 90% to 100% by solid weight of EGCg.

[053] In addition, in certain embodiments disclosed herein, the green tea extract may contain about 0%> to about 20%> by solid weight of EC, including from about 4% to about 15%, and from about 5% to about 10% by solid weight of EC. In accordance with certain embodiments, the EC content of the compositions disclosed herein may be fortified or supplemented by including sources of EC other than green tea extract, such as cocoa.

[054] The compositions of the present disclosure may provide from about 20 mg/day to about 2,000 mg/day of GTE in accordance with the methods described herein. Accordingly, the compositions may include about 40 mg/day to about 2,000 mg/day of GTE, including from about 100 mg/day to about 2,000 mg/day, from about 250 mg/day to about 2,000 mg/day, from about 500 mg/day to about 2,000 mg/day, from about 750 mg/day to about 2,000 mg/day, from about 20 mg/day to about 1,500 mg/day, from about 20 mg/day to about 1,000 mg/day, from about 20 mg/day to about 750 mg/day, from about 20 mg/day to about 500 mg/day, from about 20 mg/day to about 250 mg/day, and from about 20 mg/day to about 100 mg/day of GTE.

[055] In certain embodiments, the compositions of the present disclosure comprise

HMB and GTE in a weight ratio (HMB:GTE) of from about 0.5: 1 to about 10: 1. In other embodiments, the weight ratio of HMB: GTE in the composition is from about 1 :1 to about 7: 1, including from about 1.5 : 1 to about 6:1, and including from about 2: 1 to about 5: 1.

Product Form

[056] The HMB and GTE are formulated into a suitable composition and then, in accordance with the methods disclosed herein, administered to a subject in a form adapted to the chosen route of administration. In certain embodiments, the compositions disclosed herein include, but are not limited to, those suitable for oral administration. Oral administration, as used herein, refers to any form of administration in which the composition including HMB and GTE passes through the esophagus of the subject. For example, oral administration typically refers to oral consumption, but may also include other forms of enteral administration (i.e., administration through the digestive track). Other forms of enteral administration suitable for use with the methods disclosed herein include nasogastric, gastric, or jejunal intubation.

[057] In certain embodiments, the compositions including the HMB and GTE disclosed herein are formulated as medicaments. In certain embodiments, suitable forms of the composition as a medicament include caplets, tablets, pills, capsules, chewable tablets, quick dissolve tablets, effervescent tablets, solutions, suspensions, emulsions, multi-layer tablets, bi- layer tablets, soft gelatin capsules, hard gelatin capsules, lozenges, chewable lozenges, beads, granules, particles, microparticles, sachets, and combinations thereof. In one exemplary embodiment, the composition may be in the form of a powder or liquid concentrate packaged in a sachet, the contents of which may be added to water or other potable liquid to form a beverage.

[058] In certain embodiments, the compositions containing the HMB and GTE are formulated as nutritional compositions. Such nutritional compositions disclosed herein are useful in providing supplemental, primary, or sole sources of nutrition, including providing the subjects one or more benefits as described herein. Suitable nutritional compositions for oral administration include solid, liquid, semi-solid, and semi-liquid nutritional products.

[059] Non-limiting examples of solid nutritional product forms suitable for use in the methods herein include snack and meal replacement products, including: bars; sticks; cookies, breads, cakes, or other baked goods; frozen liquids; candy; breakfast cereals; powders, granulated solids, or other particulates; molded or compressed powders; snack chips or bites; frozen or retorted entrees; and so forth.

[060] Nonlimiting examples of liquid nutritional product forms suitable for use herein include snack and meal replacement products, hot or cold beverages, carbonated or non- carbonated beverages, juices or other acidified beverages, milk or soy-based beverages, shakes, coffees, teas, low-volume liquid "shooters," enteral feeding compositions, and so forth. These liquid compositions are most typically formulated as suspensions or emulsions, but can also be formulated in any other suitable forms such as clear liquids, substantially clear liquids, solutions, and so forth.

[061] As noted above, the nutritional products may be in the form of semi-solids, which include those forms that are intermediate in properties, such as rigidity, between solids and liquids. Some examples of semi-solids include puddings, gelatins, and doughs.

[062] Additionally as noted, the nutritional products may be in the form of semi-liquids, which include those forms that are intermediate in properties, such as flow properties, between liquids and solids. Exemplary semi-liquids include thick shakes and liquid gels. [063] The quantity of nutritional composition that provides effective amounts of HMB and GTE to the subject may be administered as a single serving or as multiple servings per day.

[064] In certain embodiments, the nutritional composition provides up to 500 kilocalories (kcal) of energy per serving or dose, including from 20 kcal to 500 kcal, from 75 kcal to 500 kcal, from 150 kcal to 500 kcal, from 250 kcal to 500 kcal, from 300 kcal to 500 kcal, or from 400 kcal to 500 kcal per serving.

Macronutrients

[065] As mentioned above, in accordance with certain embodiments, the compositions disclosed herein may be nutritional compositions which include at least one of a source of protein, a source of carbohydrate, and a source of fat. The amount or concentration of the at least one source of protein, source of carbohydrate, and source of fat present in the nutritional compositions may vary widely depending on the product formulation of the nutritional composition (e.g., clear liquid, fat-based emulsion). In addition, the amount or concentration of the at least one source of protein, source of carbohydrate, and source of fat may be characterized based upon a percentage of the total calories per serving in the nutritional composition. For example, in certain embodiments, the amount or concentration of the at least one source of protein, source of carbohydrate, and source of fat present in the nutritional composition can be within the ranges described in Samples A-E, as shown in Table 1 below.

Table 1

[066] In certain embodiments in which the nutritional composition contains a source of protein, the source of protein is present in the nutritional composition in an amount sufficient to provide 5 g/serving to 50 g/serving of protein, including from 6 g/serving to 45 g/serving and from 10 g/serving to 30 g/serving of protein.

[067] Any source of protein may be used so long as it is suitable for nutritional compositions and is otherwise compatible with any other selected ingredients or features in the nutritional composition. For example, the at least one source of protein may include, but is not limited to, intact, hydrolyzed, and partially hydrolyzed protein, which may be derived from any known or otherwise suitable source such as milk (e.g., casein, whey), animal (e.g., meat, fish), cereal (e.g., rice, corn), vegetable (e.g., soy, potato, pea), and combinations thereof. The at least one source of protein may also include a mixture amino acids (often described as free amino acids) known for use in nutritional products or a combination of such amino acids with the intact, hydrolyzed, and partially hydrolyzed proteins described herein. The amino acids may be naturally occurring or synthetic amino acids.

[068] Examples of suitable sources of protein for use in the nutritional compositions disclosed herein include, but are not limited to, whey protein concentrates, whey protein isolates, whey protein hydrolysates, acid caseins, sodium casemates, calcium casemates, potassium casemates, casein hydrolysates, milk protein concentrates, milk protein isolates, milk protein hydrolysates, nonfat dry milk, condensed skim milk, soy protein concentrates, soy protein isolates, soy protein hydrolysates, pea protein concentrates, pea protein isolates, pea protein hydrolysates, collagen proteins, potato proteins, rice proteins, insect proteins, earthworm proteins, fungal (e.g., mushroom) proteins, proteins expressed by microorganisms (e.g., bacteria and algae), and the like, as well as combinations thereof. The nutritional compositions can include any individual source of protein or a combination of two or more of the various sources of protein listed above or otherwise encompassed by the general inventive concepts.

[069] In accordance with certain embodiments in which the composition is a nutritional composition and contains a source of carbohydrate, the source of carbohydrate is present in an amount sufficient to provide the nutritional composition 15 g/serving to 1 10 g/serving of carbohydrate, including from 25 g/serving to 90 g/serving and from 40 g/serving to 65 g/serving of carbohydrate. [070] Carbohydrates suitable for use in the nutritional compositions disclosed herein may be simple, complex, variations, or combinations thereof. Any source of carbohydrate may be used so long as it is suitable for use in nutritional compositions and is otherwise compatible with any other selected ingredients or features present in the nutritional composition. Non- limiting examples of a source of carbohydrate suitable for use in the nutritional compositions disclosed herein include: maltodextrin; hydro lyzed or modified starch or cornstarch; glucose polymers; corn syrup; corn syrup solids; rice-derived carbohydrates; high fructose corn syrup; honey; sugar alcohols, such as maltitol, erythritol, sorbitol, glycerin, and the like; sucrose; glucose; fructose; lactose; isomaltulose, sucromalt, pullulan, potato starch, and other slowly- digested carbohydrates; oligosaccharides such as fructo-oligosaccharides; dietary fibers including, but not limited to, oat fiber, soy fiber, gum arabic, sodium carboxymethylcellulose, methylcellulose, guar gum, gellan gum, locust bean gum, konjac flour, hydroxypropyl methylcellulose, tragacanth gum, karaya gum, gum acacia, chitosan, arabinogalactans, glucomannan, xanthan gum, alginate, pectin, low and high methoxy pectin, cereal beta-glucans (e.g., oat beta-glucan, barley beta-glucan), carrageenan and psyllium, soluble dietary fibers such as digestion resistant maltodextrins (e.g. , Fibersol™), resistant modified food starches (e.g., Actistar™), and other resistant starches; soluble and insoluble fibers derived from fruits or vegetables; and combinations thereof. The nutritional compositions can include any individual source of carbohydrate or a combination of two or more of the various sources of carbohydrate listed above or otherwise encompassed by the general inventive concepts.

[071] In accordance with certain embodiments in which the composition is a nutritional composition and contains a source of fat, the source of fat is present in an amount sufficient to provide the nutritional composition about 0.1 g/serving to about 45 g/serving of fat, including from about 5 g/serving to about 35 g/serving and from about 10 g/serving to about 30 g/serving of fat. In certain embodiments of the nutritional composition containing at least one source of fat, the nutritional composition is in the form of a liquid emulsion.

[072] Any source of fat may be used so long as it is suitable for use in nutritional compositions and is otherwise compatible with any other selected ingredients or features present in the nutritional composition. The source of fat may be derived from plants, animals, and combinations thereof. Non-limiting examples of suitable sources of fat for use in the nutritional compositions described herein include coconut oil, fractionated coconut oil, soy oil, corn oil, olive oil, safflower oil, high oleic acid safflower oil, medium chain triglyceride oil, high gamma linolenic acid (GLA) safflower oil, sunflower oil, high oleic acid sunflower oil, palm oil, palm kernel oil, palm olein, canola oil, marine oils, fish oils, algal oils, transgenic oils, cottonseed oils, interesterified oils, transesterified oils, eicosapentaenoic acid, docosahexaenoic acid, and the like, as well as combinations thereof. The nutritional compositions can include any individual source of fat or a combination of two or more of the various sources of fat listed above or otherwise encompassed by the general inventive concepts.

Optional components

[073] In certain embodiments, the nutritional powders described herein may further comprise other optional ingredients that may modify the physical, chemical, hedonic, or processing characteristics of the products or serve as additional nutritional components when used for a targeted population. Many such optional ingredients are known or otherwise suitable for use in other nutritional products and may also be used in the nutritional powders described herein, provided that such optional ingredients are safe and effective for oral administration and are compatible with the essential and other ingredients in the selected product form.

[074] In certain embodiments, the nutritional compositions may include other compounds or sources of such compounds that are anabolic for muscle, stimulate muscle protein synthesis, decrease muscle protein degradation, or combinations thereof. Examples of such compounds include, but are not limited to, leucine, isoleucine, valine, glycine, histidine, lysine, methionine, phenylalanine, threonine, tryptophan, carnitine, carnosine, creatine, taurine, arginine, anserine, mushroom extract, cordycepic acid, spinach extract, arugula extract, broccoli extract, eggplant skin extract, plum extract, apple extract, ursolic acid, grape extract, resveratrol, bioidentical stilbenes such as pTeroPure™, olive extract, and metabolites of any of the foregoing. In accordance with one or more embodiments, the nutritional compositions include at least one source of a compound selected from the group consisting of leucine, isoleucine, valine, glycine, histidine, lysine, methionine, phenylalanine, threonine, tryptophan, carnitine, carnosine, creatine, and metabolites of any of the foregoing, as well as combinations thereof. [075] In certain embodiments, the compositions may include a high intensity sweetener to counter, mask, or otherwise obscure the potent taste of the green tea extract, particularly the EGCg present in the green tea extract, which may be described as sour, astringent, and bitter, as well as to counter, mask, or otherwise obscure the taste of any of the other polyphenols in the green tea extract that may be present in the composition. Examples of suitable high intensity sweeteners include, but are not limited to, sucralose, acesulfame potassium (also known as "acesulfame K" or "ace K"), aspartame, stevia, neotame, neohesperidine DC, alitame, monellin, thaumatin, mogrosides, monk fruit, and the like. Combinations of the high intensity sweeteners listed above may be used. The amount of the high intensity sweetener in the composition may vary depending upon the particular high intensity sweetener selected, other ingredients in the formulation, and other formulation or product target variables. Different high intensity sweeteners themselves have different sweetness intensities (e.g. , acesulfame K is approximately 200 times sweeter than sucrose, as compared to sucralose which is approximately 600 times sweeter than sucrose), and therefore may require more or less sweetener relative to other sweeteners. Furthermore, certain carbohydrates, which may already be present in the compositions disclosed herein, are sweeteners that may at least partially counter or at least partially mask the taste of the green tea extract in such compositions.

[076] In certain embodiments, the liquid compositions disclosed herein may comprise a viscosity agent, e.g., thickening agent. Typically, the viscosity agent is used in the thicker types of liquid compositions, for example, fat-based emulsions, shakes, etc. Any viscosity agent that is known or otherwise suitable for use in a composition is also suitable for use herein, some non- limiting examples of which include starches, such as modified corn starch, wheat starch (including pregelatinized wheat starch), potato starch, rice starch, tapioca starch, and the like; blends of cellulose gel and cellulose gum; blends of micro crystalline cellulose and sodium carboxymethyl cellulose; pectin; carrageenan; agar; gellan gum; alginates; gum acacia; gelatin; methyl cellulose; hydroxypropylcellulose; and combinations thereof. In certain embodiments, the viscosity agent is present in an amount of 0% to about 5.0%, including from about 0.1% to about 3%), including from about 0.5%> to about 1.5%, by solid weight based on the total weight of the composition. [077] In certain embodiments, the powder compositions disclosed herein include at least one wetting agent. Generally, wetting agents act to improve and hasten the interaction between the powder composition and the impinging liquid (e.g., water). The wetting agent thus assists in more quickly reconstituting the powder composition into a suitable liquid composition. Suitable wetting agents include phospholipids, mono- and diglycerides, mono- and diglyceride oil, diacetyl tartaric acid ester of mono- and diglycerides (DATEM), and other emulsifiers and surfactants.

[078] In certain embodiments, the powder compositions disclosed herein include at least one anti-caking agent. Generally, these agents help to maintain the powder particles as loose, free-flowing particles with a reduced tendency to form large clumps as the powder sits over time. Silicon dioxide is an example of one suitable anti-caking agent.

[079] In certain embodiments, the compositions disclosed herein may comprise one or more compounds selected from beta-alanine, human milk oligosaccharides, prebiotics, probiotics, nucleotides, nucleosides, carotenoids (e.g., lutein, beta-carotene, lycopene, and zeaxanthin), and combinations thereof.

[080] Furthermore, the compositions disclosed herein may also contain other ingredients, non-limiting examples of which include, preservatives, antioxidants in addition to those found in the GTE, buffers, pharmaceutical actives, additional nutrients, colorants, flavors, emulsifiers, anti-foaming agents, and the like.

[081] In certain embodiments, the compositions may also contain vitamins or related nutrients including, but not limited to, curcumin, fish oil, vitamin A, vitamin D (cholecalciferol, 25 -hydro xycholecalciferol, 1 ,25 -dihydroxy cholecalciferol, 24,25-dihydroxycholecalciferol, ergocalciferol), vitamin E, vitamin Kl , vitamin K2, thiamine, riboflavin, pyridoxine, vitamin B12, niacin, folic acid, pantothenic acid, biotin, vitamin C, choline, inositol, salts, derivatives thereof, and combinations thereof.

[082] Additionally, in certain embodiments, the compositions disclosed herein may also contain minerals including, but not limited to, calcium, phosphorus, magnesium, iron, manganese, copper, sodium, potassium, molybdenum, chromium, selenium, chloride, zinc, and combinations thereof.

[083] Exemplary formulations of liquid nutritional compositions in accordance with embodiments disclosed herein are provided below in Tables 2 and 3. All ingredient amounts listed in Tables 2 and 3 are listed as kilogram per 1000 kg batch of product, unless otherwise indicated.

[084] Table 2 shows an exemplary formulation of an emulsion-type liquid nutritional composition containing protein, carbohydrate, fat, HMB and GTE. Assuming a density of 1.075 g/mL and a serving size of about 237 mL (about 8 fl. oz.), a nutritional composition made according to the formulation shown in Table 2 has about 1.5 g calcium HMB monohydrate and about 500 mg of GTE per serving.

Table 2

y roc o e, y oxne y roc or e, o avn, o c c , otn, yanoco aamn, etc.

[085] Table 3 shows an exemplary formulation of a clear-type liquid nutritional composition that is substantially free of fat and contains protein, carbohydrate, HMB and GTE. Assuming a density of 1.05 g/mL and a serving size of about 237 mL (about 8 fl. oz.), a nutritional composition made according to the formulation shown in Table 3 has about 1.5 g calcium HMB monohydrate and about 500 mg of GTE per serving.

Table 3

Methods of Manufacture

[086] The various embodiments of exemplary compositions disclosed herein may be prepared by any process or suitable method (now known or known in the future) for making the selected product form, such as a powder, solid, semi-solid, liquid, or semi-liquid nutritional composition. The manufacturing processes for the compositions of the present disclosure may be carried out in ways other than those set forth herein without departing from the spirit and scope of the present disclosure. The present embodiments are, therefore, to be considered in all respects illustrative and not restrictive, and all changes and equivalents also come within the description of the present disclosure.

[087] In one suitable manufacturing process for preparing emulsion-type liquid nutritional compositions, at least three separate slurries are prepared, including a protein-in-fat (PIF) slurry, a carbohydrate-mineral (CHO-MIN) slurry, and a protein-in-water (PIW) slurry. The PIF slurry is formed by heating and mixing an oil (e.g. , soy oil, canola oil or corn oil) and then adding an emulsifier (e.g., lecithin), fat soluble vitamins, and a portion of the total protein (e.g., milk protein concentrate) with continued heat and agitation. The CHO-MIN slurry is formed by adding with heated agitation to water: minerals (e.g., potassium citrate, dipotassium phosphate, or sodium citrate), including trace and ultra trace minerals (e.g., Ultra Trace Mineral/Trace Mineral Premix), thickening or viscosity agents (e.g., cellulose gel, gellan, or carrageenan), and HMB, typically as calcium HMB. The resulting CHO-MIN slurry is held for 10 minutes with continued heat and agitation before adding additional minerals (e.g., potassium chloride, magnesium carbonate, or potassium iodide) and the carbohydrates (e.g., sucrose or corn syrup). The PIW slurry is formed by mixing with heat and agitation the remaining protein with water.

[088] In accordance with this exemplary process, the three slurries are blended together with heat and agitation and the pH is adjusted to the desired range, e.g., from 6.6 to 7, after which the composition is subjected to high-temperature short-time ("HTST") processing. The composition is heat treated, emulsified, homogenized, and cooled during HTST. Water soluble vitamins and ascorbic acid are added (if applicable), the pH is again adjusted (if necessary), flavors are added, and any additional water can be added to adjust the solids content to the desired range. The green tea extract is prepared as a solution (e.g., 1% w/w) by adding GTE to water and agitating for 0-24 hours. The solution of green tea extract is added to the composition containing the other ingredients and is agitated for a period of time (e.g., 5 to 60 minutes) to ensure homogeneous distribution of the green tea extract in the composition. The agitation associated with the preparation of the solution containing the green tea extract, as well as the agitation associated with the addition of such green tea extract solution to the other ingredients, may take place at 4° C to 50° C. At this point, the liquid nutritional composition may optionally be sterilized according to any suitable sterilization technique (e.g., aseptic, retort, hot-fill, chemical, radiation, and filtering sterilization techniques) and packaged.

[089] In certain embodiments, a liquid nutritional composition is dried to form a nutritional powder using any methods known in the art. By way of example, nutritional powders can be manufactured by preparing one or more slurries, as described above, which are then mixed, heat treated, standardized, heat treated a second time, evaporated to remove water, and spray dried or dry blended to form a reconstitutable nutritional powder. For example, the spray drying may include any spray drying technique that is suitable for use in the production of nutritional powders. Many different spray drying methods and techniques are known for use in the nutrition field, all of which are suitable for use in the manufacture of the spray dried nutritional powders herein. Following drying, the finished powder may be packaged into any suitable container (e.g., a metal canister or plastic jar).

[090] In other embodiments, the method for preparing the nutritional powder comprises preparing an extruded powder. In certain embodiments, the dry ingredients of the nutritional powder are incorporated in the extruder hopper in the form of a dry feed or powder premix. The dry nutritional ingredients enter the extruder just after the point of entry of water. In certain embodiments, the water comprises from about 1% to about 80% by weight of the total weight of the water and dry ingredients. The amount of water added to the nutritional composition may be adjusted within the aforementioned ranges based on the desired physical properties of the extrudate. In certain embodiments, the nutritional ingredients may be premixed with water to form a thick emulsion, which is then fed into the extruder hopper in the form of a viscous liquid or sludge. The term "extrudate" refers to all or a portion of a nutritional composition that exits an extruder.

[091] In certain embodiment, the extruder used to produce the nutritional powder or extrudate operates in a continuous format. Generally, any extruder known for use in food processing may be utilized. In certain embodiments, extrusion is performed via a screw extruder. Said screw extruder may be a twin screw extruder or a single screw extruder. The extruder screws may consist of shear elements, mixing elements, conveying elements, kneading elements, emulsifying elements, disc elements, or a combination of the above in any interchangeable order. The barrels of the extruder may be steam heated or electrically heated. In certain embodiments, extrusion takes place at a temperature between about 20 °C to about 99 °C, from about 30 °C to about 150 °C, or from about 70 °C to about 100 °C. In certain embodiments, the ingredients are processed in the extruder for about 5 seconds to about 240 seconds or for about 30 seconds to about 180 seconds.

[092] In certain embodiments disclosed herein, the extrudate is dried following extrusion so as to remove most or all of the water contained therein. In such embodiments, any conventional drying methods may be used to remove the desired amount of water from the nutritional powder. For example, the nutritional powder extrudate may be dried using a vacuum, convective hot air, a tray dryer, infrared, or any combination of the above. In certain embodiments, the nutritional powder extrudate may be further ground or milled to a desired particle size following drying. In certain embodiments, additional protein and carbohydrate ingredients may be added to the final nutritional powder in the form of dry ingredients or a dry blend.

Methods of Preserving Muscle Strength

[093] The compositions containing HMB and GTE are administered orally in accordance with the present disclosure to a subject as needed to preserve muscle strength during a period of muscle disuse or muscle recovery. The period of muscle disuse may be due to any number of reasons, including for example partial or full immobilization, casting, injury, illness, bed rest, hospitalization, extended air travel, weightlessness, and the like, as noted above. The compositions containing HMB and GTE may be administered to a subject solely during the period of muscle disuse or solely during the period of muscle recovery. However, to preserve muscle strength more fully, it is generally desirable to administer the composition containing HMB and GTE to the subject during at least a portion of both the period of muscle disuse and the period of muscle recovery. In certain embodiments, the composition containing HMB and GTE is administered to the subject for the entire, or substantially entire, period of muscle disuse and the entire, or substantially entire, period of muscle recovery.

[094] The subject may be a child or an adult who is susceptible to loss of muscle strength due to muscle disuse resulting from a portion of the subject's body being immobilized in a cast. The subject may be a child or an adult who is susceptible to loss of muscle strength due to muscle disuse as a result of a severe illness such as cancer. The subject may be a child or an adult who is susceptible to loss of muscle strength due to muscle disuse that occurs while recovering from surgery. The subject may be a child or an adult who is susceptible to loss of muscle strength due to muscle disuse that occurs during hospitalization. The subject may be a child, a pregnant woman, or an adult who is susceptible to loss of muscle strength due to muscle disuse that occurs during prolonged bed rest. The subject may be a child or an adult who is susceptible to loss of muscle strength due to extended air travel, i.e., flights that are at least 4 hours in duration. The subject may be an adult who is susceptible to loss of muscle strength due to muscle disuse resulting from time spent in low-gravity conditions. The subject may be an adult or older adult who is susceptible loss of muscle strength due to muscle disuse resulting from prolonged inactivity.

[095] In certain embodiments, the compositions including HMB and GTE can be administered to subjects during periods of muscle disuse. In certain embodiments, the compositions disclosed herein are administered to the subject when the period of muscle disuse lasts at least 4 hours. In certain embodiments, the compositions are administered to the subject when the period of muscle disuse lasts from about 4 hours to about 72 hours, including from about 4 hours to about 48 hours, including from about 4 hours to about 24 hours, including from about 4 hours to about 12 hours, including from about 8 hours to about 72 hours, including from about 8 hours to about 48 hours, including from about 8 hours to about 24 hours, including from about 12 hours to about 72 hours, including from about 12 hours to 48 hours, and including from about 12 hours to about 24 hours. In other embodiments, the compositions are administered to the subject when the period of muscle disuse lasts from about 24 hours to about 36 months, including from about 24 hours to about 24 months, including from about 24 hours to about 12 months, including from about 24 hours to about 6 months, including from about 24 hours to about 3 months, including from about 24 hours to about 2 months, including from about 24 hours to about 1 month, including from about 24 hours to about 2 weeks, including from about 24 hours to about 1 week, including from about 48 hours to about 36 months, including from about 48 hours to about 24 months, including from about 48 hours to about 12 months, including from about 48 hours to about 6 months, including from about 48 hours to about 3 months, including from about 48 hours to about 2 months, including from about 48 hours to about 1 month, including from about 48 hours to about 2 weeks, including from about 48 hours to about 1 week, including from about 72 hours to about 12 months, including from about 72 hours to about 6 months, including about 72 hours to about 3 months, including from about 72 hours to about 1 month, including from about 72 hours to 2 weeks, including from about 72 hours to about 1 week, including from about 1 week to about 12 months, including about 1 week to about 6 months, including from about 1 week to about 3 months, including from about 1 week to about 1 month, including from about 2 weeks to about 12 months, including from about 3 weeks to about 12 months, including from about 4 weeks to about 12 months, including about 6 weeks to 12 months, including from about 2 months to about 12 months, including from about 3 months to about 36 months, including from about 3 months to about 24 months, and including from about 3 months to about 12 months. In accordance with the preceding and other embodiments, the compositions disclosed herein can be administered to a subject for a period of muscle disuse lasting at least 4 hours, at least 8 hours, at least 12 hours, at least 24 hours, at least 48 hours, at least 72 hours, at least 1 week, at least 10 days, at least 2 weeks, at least 1 month, at least 3 months, at least 6 months, at least 12 months, at least 24 months, at least 36 months, or for more than 36 months.

[096] In certain embodiments, the compositions including HMB and GTE can be administered to subjects during periods of muscle disuse, as discussed above, and during subsequent periods of muscle recovery. In certain embodiments, the compositions disclosed herein are administered to the subject when the period of muscle recovery lasts at least 4 hours. In certain embodiments, the compositions are administered to the subject when the period of muscle recovery lasts from about 4 hours to about 72 hours, including from about 4 hours to about 48 hours, including from about 4 hours to about 24 hours, including from about 4 hours to about 12 hours, including from about 8 hours to about 72 hours, including from about 8 hours to about 48 hours, including from about 8 hours to about 24 hours, including from about 12 hours to about 72 hours, including from about 12 hours to 48 hours, and including from about 12 hours to about 24 hours. In other embodiments, the compositions are administered to the subject when the period of muscle recovery lasts from about 24 hours to about 36 months, including from about 24 hours to about 24 months, including from about 24 hours to about 12 months, including from about 24 hours to about 6 months, including from about 24 hours to about 3 months, including from about 24 hours to about 2 months, including from about 24 hours to about 1 month, including from about 24 hours to about 2 weeks, including from about 24 hours to about 1 week, including from about 48 hours to about 36 months, including from about 48 hours to about 24 months, including from about 48 hours to about 12 months, including from about 48 hours to about 6 months, including from about 48 hours to about 3 months, including from about 48 hours to about 2 months, including from about 48 hours to about 1 month, including from about 48 hours to about 2 weeks, including from about 48 hours to about 1 week, including from about 72 hours to about 12 months, including from about 72 hours to about 6 months, including about 72 hours to about 3 months, including from about 72 hours to about 1 month, including from about 72 hours to 2 weeks, including from about 72 hours to about 1 week, including from about 1 week to about 12 months, including about 1 week to about 6 months, including from about 1 week to about 3 months, including from about 1 week to about 1 month, including from about 2 weeks to about 12 months, including from about 3 weeks to about 12 months, including from about 4 weeks to about 12 months, including about 6 weeks to 12 months, including from about 2 months to about 12 months, including from about 3 months to about 36 months, including from about 3 months to about 24 months, and including from about 3 months to about 12 months. In accordance with the preceding and other embodiments, the compositions disclosed herein can be administered to a subject for a period of muscle recovery lasting at least 4 hours, at least 8 hours, at least 12 hours, at least 24 hours, at least 48 hours, at least 72 hours, at least 1 week, at least 10 days, at least 2 weeks, at least 1 month, at least 3 months, at least 6 months, at least 12 months, at least 24 months, at least 36 months, or for more than 36 months.

[097] Within the context of administering a serving to a subject, the number of days is intended to reflect the days in which the subject has been instructed to be administered the composition, and in which the composition is actually administered for at least 65%, including at least 70%, including at least 75%, including at least 80%, and including at least 90% of the instructed days during the period of administration.

[098] The compositions described herein may be provided to the subject in the form of servings. The compositions may, but are not limited to, being administered as one serving per day, two servings per day, three servings per day, four servings per day, etc. Typically, the compositions disclosed herein are administered in at least one serving per day or at least two servings per day. In other embodiments, the compositions disclosed herein are administered continuously or intermittently up to 24 hours per day by infusion through a nasogastric, gastric, or jejunal feeding tube. In certain embodiments, when the composition is a solid or powdered nutritional product, the serving is within a range of from about 25 g to 500 g, including from about 50 g to about 400 g, including from about 75 g to about 300 g, including from about 100 g to about 250 g, and including from about 150 g to about 200 g. When the composition is a liquid nutritional product, the serving is within a range of about 5 mL to about 500 mL, including from about 25 mL to about 500 mL, including from about 50 mL to 450 mL, including from about 100 mL to 400 mL, including from about 150 mL to about 400 mL, including from about 175 mL to about 350 mL, including from about 200 mL to about 300 mL, and including from about 230 mL to about 250 mL.

[099] In certain embodiments, the methods disclosed herein prevent the loss of skeletal muscle strength in a subject during a period of muscle disuse. In certain embodiments, the methods disclosed herein prevent the loss of skeletal muscle strength in a subject during a period of muscle disuse and during a subsequent period of muscle recovery. EXAMPLES

[0100] The following examples illustrate specific and exemplary embodiments and/or features of the methods disclosed herein. The examples are provided solely for the purposes of illustration and should not be construed as limitations of the present disclosure. Numerous variations over these specific examples are possible without departing from the spirit and scope of the general inventive concepts.

[0101] To study the effects of HMB and GTE on muscle strength during extended muscle disuse, unilateral hind limb casting (i.e., immobilization) was carried out on adult (8 month) Sprague Dawley (SD) rats. Unilateral hind limb casting was carried out for 7 days, followed by 7 days of muscle recovery after cast removal.

[0102] SD rats were randomly assigned to one of 5 groups: one non-casted control group, one casted/recovery control group, and three casted/recovery test groups. Each group was fed ad libitum one of the following assigned diets, as provided in Table 4, for the duration of the test, beginning 7 days prior to initiation of casting and over the entire casting and recovery periods.

Table 4

[0103] AIN-93M diets are well known balanced diets for rodents containing 12% protein.

The SD rats were assumed to have an approximate body weight of 500 g and an approximate food intake of 20 g/day. The AIN-93M diet was supplemented with: a) HMB at a concentration of 8.5 gm/kg in the test diet, to deliver a dose of 340 mg/kg body weight of HMB per day to the Group 3 SD rats; b) GTE at a concentration of 1.25 gm/kg in the test diet, to deliver a dose of 50 mg/kg body weight of GTE per day to the Group 4 SD rats; or c) HMB at a concentration of 8.5 gm/kg plus GTE at a concentration of 1.25 g/kg in the test diet, to deliver a dose of 340 mg/kg body weight of HMB and 50 mg/kg body weight per day to the Group 5 SD rats.

[0104] At the end of the study, the animals were deeply anaesthetized and in situ muscle force measurements were performed on the animals' plantaris muscles. Muscle strength (force) performance was assessed using an Aurora Scientific 1305 A Rat Test System. The sciatic nerve of each limb was stimulated at various frequencies between 1 and 200 Hz for 200 ms each, with a 30 s rest between each pulse, and the force produced by the stimulated muscle was measured. Both the immobilized hind limb and the free (non-immobilized) hind limb for each rat were tested. The animals were sacrificed afterward.

[0105] Fig. 1 is a graph showing the force results for the non-immobilized limb of the SD rats taken at the end of the 7 day immobilization plus 7 day recovery period. No significant effect of dietary supplementation on muscle force production was observed in the plantaris muscle of the non-immobilized limb for any group. Fig. 2 is a graph showing the force results for the immobilized limb of the SD rats taken at the end of the 7 day immobilization plus 7 day recovery period. In the immobilized limb, at lower test frequencies, the force produced by the plantaris muscle of the control non-casted group (Control, Group 1) was significantly less compared to all other groups of animals. However, the force produced by Group 5, who received both HMB and GTE supplementation, was greater than that produced by the other groups, including HMB alone or GTE alone. The force produced by Group 5 was also significantly greater than that produced by most other groups at all test frequencies. These data indicate that the combination of HMB plus GTE synergize to improve muscle force recovery following a period of immobilization. This could have clinical relevance for muscle recovery from muscle disuse due to partial or full immobilization, casting, injury, illness, bed rest, hospitalization, long airline flights {e.g., at least 4 hours or longer), weightlessness, and the like.

[0106] While the present application has been illustrated by disclosing various exemplary embodiments of the general inventive concepts, and while the exemplary embodiments have been described in considerable detail, it is not the intention of the applicants to restrict or in any way limit the scope of the appended claims or general inventive concepts to such detail. Additional advantages and modifications will readily appear to those skilled in the art. Therefore, the application, in its broader aspects, is not limited to the specific details, the representative apparatus, and illustrative examples shown and described. Accordingly, departures may be made from such details without departing from the spirit or scope of the general inventive concepts as taught and suggested by the disclosure herein.

[0107] To the extent that the terms "includes," "including," "contains," or "containing" are used in the specification or the claims, they are intended to be inclusive in a manner similar to the term "comprising" as that term is interpreted when employed as a transitional word in a claim. Furthermore, to the extent that the term "or" is employed (e.g., A or B) it is intended to mean "A or B or both." When the applicants intend to indicate "only A or B but not both" then the term "only A or B but not both" will be employed. Thus, use of the term "or" herein is the inclusive, and not the exclusive use. As used in the description of the invention and the appended claims, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise.

[0108] All percentages, parts, and ratios as used herein are by weight of the total product, unless specified otherwise. All such weights as they pertain to listed ingredients are based on the active ingredients and, therefore, do not include solvents or by-products that may be included in commercially available materials, unless specified otherwise.

[0109] All references to singular characteristics or limitations of the present disclosure shall include the corresponding plural characteristics or limitations, and vice versa, unless otherwise specified or clearly implied to the contrary by the context in which the reference is made.

[01 10] All combinations of method or process steps as used herein can be performed in any order, unless otherwise specified or clearly implied to the contrary by the context in which the referenced combination is made.

[01 1 1] All ranges and parameters, including but not limited to percentages, parts, and ratios, disclosed herein are understood to encompass any and all sub-ranges assumed and subsumed therein, and every number between the endpoints. For example, a stated range of "1 to 10" should be considered to include any and all sub-ranges beginning with a minimum value of 1 or more and ending with a maximum value of 10 or less (e.g., 1 to 6.1 , or 2.3 to 9.4), and to each integer (1 , 2, 3, 4, 5, 6, 7, 8, 9, and 10) contained within the range.

[01 12] The various embodiments of the compositions of the present disclosure may include trace amounts of any optional or selected essential ingredient or feature described herein, provided that the remaining formulation still contains all of the required ingredients or features as described herein. In this context, and unless otherwise specified, the term "trace amount" means that the selected formulation contains no more than 2 wt% of the optional ingredient, typically less than 1 wt%, and also includes zero percent, of such optional or selected essential ingredient, by weight of the compositions.

[01 13] The various embodiments of the compositions of the present disclosure may also be substantially free of any optional ingredient or feature described herein, provided that the remaining formulation still contains all of the required ingredients or features as described herein. In this context, and unless otherwise specified, the term "substantially free" means that the selected formulation contains less than a functional amount of the optional ingredient, typically less than about 1 wt%, including less than about 0.5 wt%, including less than about 0.1 wt%, and also including zero percent, of such optional ingredient, by weight of the compositions.