WO2014099904A1

WO2014099904A1 - Methods for enhancing motor function, enhancing functional status and mitigating muscle weakness in a subject

Info

Publication number: WO2014099904A1
Application number: PCT/US2013/075649
Authority: WO
Inventors: Sean GARVEY; Neile Edens; Robert Williams; Vikkie Mustad; David ULSTAD
Original assignee: Abbott Laboratories
Priority date: 2012-12-17
Filing date: 2013-12-17
Publication date: 2014-06-26

Abstract

Methods for enhancing motor function, enhancing functional status, and mitigating muscle weakness in a subject are provided. The methods utilize the combination of administering to the subject a nutritional composition comprising at least one source of protein and applying a vibrational stimulus to the subject.

Description

METHODS FOR ENHANCING MOTOR FUNCTION, ENHANCING FUNCTIONAL STATUS AND MITIGATING MUSCLE WEAKNESS IN A SUBJECT

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to and any benefit of U.S. Provisional Application No. 61/738,131, filed December 17, 2012, the content of which is incorporated herein by reference in its entirety.

FIELD

[0002] The present disclosure relates to methods for enhancing motor function, enhancing functional status, and mitigating muscle weakness in a subject. More particularly, the present disclosure relates to methods that combine administering to the subject a nutritional composition comprising at least one source of protein, and applying a vibrational stimulus to the subject to enhance motor function, enhance functional status, or mitigate muscle weakness (or to enhance motor function, enhance functional status, and mitigate muscle weakness).

BACKGROUND

[0003] An appropriate level of motor function is needed to lead an active and independent lifestyle. Motor function may be adversely affected by a number of conditions including, but not limited to, muscle weakness, muscle atrophy, neuronal atrophy, and declines in vestibular, visual, and proprioceptive processes. Such conditions may occur in a subject due to normal aging, inactivity, or disease-related disorders. SUMMARY

[0004] Provided herein are methods for enhancing motor function, enhancing functional status, and mitigating muscle weakness in a subject. The methods utilize the combination of administering to the subject a nutritional composition comprising at least one source of protein, and applying a vibrational stimulus to the subject. In certain embodiments, the enhanced motor function, enhanced functional status, or mitigation of muscle weakness is caused by one or more of enhanced muscle function, a reduction in muscle protein degradation, an increase in muscle protein synthesis, a reduction of muscle necrosis or apoptosis, enhanced motor coordination, enhanced balance, enhanced sensorimotor reactivity of myofibers or muscle groups that contribute to reflexes, and enhanced speed.

[0005] In a first embodiment, a method for enhancing motor function in a subject is provided. The method comprises providing to the subject a nutritional composition comprising at least one source of protein in an amount sufficient to provide 6 grams to 50 grams of protein per serving. In addition, the method includes applying to the subject a vibrational stimulus having a frequency of 10 Hz to 120 Hz and an amplitude of 0.1 g to 20 g. The consumption of the nutritional composition by the subject and application of the vibrational stimulus result in enhanced motor function.

[0006] In a second embodiment, a method for enhancing the functional status of a subject is provided. The method comprises providing a nutritional composition to a subject having or at risk of having reduced functional status. The nutritional composition comprises at least one source of protein in an amount sufficient to provide 6 grams to 50 grams of protein per serving. In addition, the method includes applying to the subject a vibrational stimulus having a frequency of 10 Hz to 120 Hz and an amplitude of 0.1 g to 20 g. The consumption of the nutritional composition by the subject and application of the vibrational stimulus result in enhanced functional status.

[0007] In a third embodiment, a method for mitigating muscle weakness in a subject is provided. The method comprises providing a nutritional composition to a subject having or at risk of having muscle weakness. The nutritional composition comprises at least one source of protein in an amount sufficient to provide 6 grams to 50 grams of protein per serving. In addition, the method includes applying to the subject a vibrational stimulus having a frequency of 10 Hz to 120 Hz and an amplitude of 0.1 g to 20 g. The consumption of the nutritional composition by the subject and application of the vibrational stimulus is effective for mitigating muscle weakness in the subject.

DETAILED DESCRIPTION

[0008] Provided herein are methods for enhancing motor function, enhancing functional status, and mitigating muscle weakness in a subject. The methods utilize the combination of administering to the subject a nutritional composition comprising at least one source of protein, and applying a vibrational stimulus to the subject.

[0009] The terminology as set forth herein is for description of the embodiments only and should not be construed as limiting the disclosure as a whole. Unless otherwise specified, "a," "an," "the," and "at least one" are used interchangeably. Furthermore, as used in the description and the appended claims, the singular forms "a," "an," and "the" are inclusive of their plural forms, unless the context clearly indicates otherwise.

[0010] 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, semisolids, semi-liquids, nutritional supplements, and any other nutritional food product known in the art. A nutritional composition in powder form may often be reconstituted to form a nutritional composition in liquid form. The nutritional compositions disclosed herein comprise at least one source of protein. In certain embodiments, the nutritional compositions comprise at least one source of protein, and at least one source of carbohydrate or at least one source of fat or both. The nutritional compositions disclosed herein are generally suitable for oral consumption by a human.

[0011] The term "subject" as used herein, unless otherwise specified, refers to mammals including, but not limited to, humans.

[0012] The term "elderly" as used herein, refers to an individual of at least 45 years of age, including at least 50 years of age, at least 55 years of age, at least 60 years of age, at least 65 years of age, at least 70 years of age, at least 75 years of age, and including at least 80 years of age or greater. The term "elderly" also includes the groups of from 45 years of age to 100 years of age, and the group of from 55 years of age to 80 years of age.

[0013] The terms "administer," "administering," "administered," and "administration" as used herein, unless otherwise specified, should be understood to include providing the nutritional product to a subject, the act of consuming the nutritional product, and combinations thereof.

[0014] The term "nutritional liquid" as used herein, unless otherwise specified, refers to nutritional compositions in ready-to-drink liquid form, concentrated liquid form, and nutritional liquids made by reconstituting nutritional powders described herein prior to use. The nutritional liquid may also be formulated as a suspension, an emulsion, a solution, and so forth.

[0015] The term "nutritional powder" or "reconstitutable powder" as used herein, unless otherwise specified, refers to nutritional compositions in flowable or scoopable form that can be reconstituted with water or another aqueous liquid prior to consumption and includes both spray dried and drymixed/dryblended powders.

[0016] 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-solids examples include puddings, yogurts, gels, gelatins, and doughs.

[0017] 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-liquids examples include thick shakes, liquid yogurts, and liquid gels.

[0018] The term "serving" as used herein, unless otherwise specified, is intended to be construed as any amount which is intended to be consumed by a subject in one sitting or within one hour or less.

[0019] The term "muscle" as used herein, unless otherwise specified, refers to skeletal muscle.

[0020] The term "muscle mass" as used herein, unless otherwise specified, refers to the amount or size of muscle or muscle groups, as expressed by muscle weight, mass, area, or volume. Muscle mass may also be expressed as total lean body mass, lean body mass of a body compartment such as the leg, or cross-sectional area of a leg or arm compartment. The volume or mass of the muscle can be determined using any known or otherwise effective technique that provides muscle area, volume or mass, such as DEXA, or using visual or imaging techniques such as MRI or CT scans.

[0021] The term "muscle atrophy" as used herein, unless otherwise specified, refers to the loss of muscle mass (also known as muscle wasting). Muscle atrophy may be caused my normal aging (e.g., sarcopenia), inactivity (e.g., muscle disuse or immobility), or disease-related disorders (e.g., cachexia).

[0022] The term "muscle strength" as used herein, unless otherwise specified, refers to the amount of force a muscle, or muscle groups in sum, can exert. Muscle strength may be evaluated by a variety of methods such as grip strength, one repetition maximum strength test, time-dependent tests of muscle endurance, time-dependent tests of muscle fatigue, or time- dependent tests of muscle endurance and fatigue, and so forth.

[0023] The term "muscle weakness" as used herein, unless otherwise specified, refers to a reduction in muscle strength, or a lack of muscle strength.

[0024] The term "muscle quality" as used herein, unless otherwise specified, refers to the amount of muscle strength (e.g., in units of force of angular velocity) per unit volume, cross- sectional area, or mass of the corresponding muscle, muscle groups, or arm or leg compartment, i.e., the term "muscle quality" refers to muscle strength per corresponding muscle volume, muscle strength per corresponding muscle cross-sectional area, or muscle strength per corresponding muscle mass. For example, leg muscle quality refers to leg muscle strength/leg muscle volume or leg muscle strength/leg muscle mass.

[0025] The term "muscle function" as used herein, unless otherwise specified, refers to at least one of muscle mass, muscle strength, and muscle quality.

[0026] The term "motor function" as used herein, unless otherwise specified, refers to the integrated measure of muscle strength, motor coordination, balance, reflexes, and speed. Motor function reflects the ability of a subject to successfully carry out a task that either requires displacement of body parts or application of force whereby displacement of body parts may not otherwise result. The task may be (1) intended, in which case the decision to initiate movement is centrally, or brain-, derived, such as walking down a flight of stairs, or (2) unintended, in which case the stimulus to initiate movement is peripherally derived, such as counteracting a slip on a flight of stairs to prevent a fall.

[0027] The term "motor coordination" as used herein, unless otherwise specified, refers to the combined result of (1) the centrally, or brain-, derived decision to initiate an intended movement; (2) secondary and rapid proprioceptive, or sensorimotor, vestibular, and visual inputs to guide the intended movement; and (3) central processing and integration of all inputs, with the net output being movement, application of force, or both. A chronic decline in motor coordination may occur in a subject, leading to a reduction in motor function, functional status, or both.

[0028] The term "functional status" as used herein, unless otherwise specified, refers to the ability of a subject to perform activities associated with normal daily living (ADLs) including, but not limited to, getting out of bed, getting off of the toilet, personal hygiene, self-feeding, performing housework, maintaining sufficient walking gait speed for safe and effective transfers, facilitating automobile-dependent transportation, and shopping for groceries. Functional status may be measured by the Katz Index of Independence in Activities of Daily Living, the Tinetti Gait and Balance Scale, the Palliative Performance Scale, the Short Physical Performance Battery, and so forth.

[0029] The term "vibrational stimulus" as used herein, unless otherwise specified, refers to a source of mechanical oscillation that is applied to the subject. The mechanical oscillation is defined by frequency (i.e., cycles of the mechanical oscillation per unit time, measured in Hz (cycles/second)) and amplitude (i.e., half the distance between the maximum magnitude and the minimum magnitude of the periodic oscillation).

[0030] The terms "applying" and "providing" as used herein within the context of providing an amount (e.g., of protein) or applying a treatment to a subject according to a certain regimen or schedule, should be understood to reflect a subject who has been instructed to be administered the active ingredients or treated according to the regimen or schedule, and who actually is administered the active ingredients or treated for at least 70% of the days during the desired period of the regimen or schedule. [0031] In a first embodiment, a method for enhancing motor function in a subject is provided. The method comprises providing to the subject a nutritional composition comprising at least one source of protein in an amount sufficient to provide 6 grams to 50 grams of protein per serving. In addition, the method includes applying to the subject a vibrational stimulus having a frequency of 10 Hz to 120 Hz and an amplitude of 0.1 g to 20 g. The consumption of the nutritional composition by the subject and application of the vibrational stimulus result in enhanced motor function.

[0032] In a second embodiment, a method for enhancing the functional status of a subject is provided. The method comprises providing a nutritional composition to a subject having or at risk of having reduced functional status. The nutritional composition comprises at least one source of protein in an amount sufficient to provide 6 grams to 50 grams of protein per serving. In addition, the method includes applying to the subject a vibrational stimulus having a frequency of 10 Hz to 120 Hz and an amplitude of 0.1 g to 20 g. The consumption of the nutritional composition by the subject and application of the vibrational stimulus result in enhanced functional status.

[0033] In a third embodiment, a method for mitigating muscle weakness in a subject is provided. The method comprises providing a nutritional composition to a subject having or at risk of having muscle weakness. The nutritional composition comprises at least one source of protein in an amount sufficient to provide 6 grams to 50 grams of protein per serving. In addition, the method includes applying to the subject a vibrational stimulus having a frequency of 10 Hz to 120 Hz and an amplitude of 0.1 g to 20 g. The consumption of the nutritional composition by the subject and application of the vibrational stimulus is effective for mitigating muscle weakness in the subject.

[0034] In certain embodiments according to the first, second, and third embodiments, the nutritional compositions are formulated as, and intended for consumption in, any known or otherwise suitable oral product form. Any solid, liquid, semi-solid, semi-liquid, or powder product form, including combinations or variations thereof, are suitable for use herein, provided that such forms allow for safe and effective oral delivery to the subject via oral consumption of the ingredients as also defined herein. [0035] In certain embodiments of the first, second, and third embodiments, the nutritional composition is a solid nutritional product. Non-limiting examples of solid nutritional products include snack and meal replacement products, including those formulated as bars, sticks, cookies or breads or cakes or other baked goods, frozen liquids, candy, breakfast cereals, powders or granulated solids or other particulates, snack chips or bites, frozen or retorted entrees and so forth. In certain embodiments according to the first, second, and third embodiments, when the nutritional composition is a solid product, the serving is within a range of 25 grams to 150 grams.

[0036] In certain embodiments of the first, second, and third embodiments, the nutritional composition is a nutritional liquid. Non-limiting examples of nutritional liquids 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, compositions for administration by nasogastric intubation, and so forth. Generally, the nutritional liquids are formulated as suspensions or emulsions, but the nutritional liquids can also be formulated in any other suitable forms such as clear liquids, solutions, liquid gels, liquid yogurts, and so forth.

[0037] In certain embodiments according to the first, second, and third embodiments, where the nutritional composition is a liquid, the serving is within a range of 30 milliliters to 500 milliliters (~1 fl. oz. to ~17 fl. oz.). In certain other embodiments according to the first, second, and third embodiments, where the nutritional composition is a liquid, the serving is 237 milliliters (~8 fl. oz.). In other embodiments according to the first, second, and third embodiments, where the nutritional composition is a liquid, the serving is 177 milliliters to 417 milliliters (~6 fl. oz. to ~14 fl. oz.). In yet other embodiments according to the first, second, and third embodiments, where the nutritional composition is a liquid, the serving is 207 milliliters to 266 milliliters (~7 fl. oz. to ~9 fl. oz.). In still other embodiments according to the first, second, and third embodiments, where the nutritional composition is a liquid, the serving is 30 milliliters to 75 milliliters (~1 fl. oz. to ~ 2.5 fl. oz.). In certain embodiments according to the first, second, and third embodiments, where the nutritional composition is administered as a liquid, one serving to 14 servings of the nutritional composition is administered to the subject per week. [0038] In yet other embodiments according to the first, second, and third embodiments, the nutritional composition may be formulated as semi-solid or semi-liquid compositions (e.g., puddings, gels, yogurts, etc.), as well as more conventional product forms such as capsules, tablets, caplets, pills, and so forth. In other embodiments of the first, second, and third embodiments, the nutritional composition may be in the form of lozenges, tablets (e.g., chewable, coated, etc.), pastes, gels, or yogurts.

[0039] The nutritional compositions disclosed herein are useful to provide sole, primary, or supplemental sources of nutrition, as well as providing one or more of the benefits as described herein. In certain embodiments according to the first, second, and third embodiments, the nutritional composition provides up to 1000 kcal of energy per serving or dose, including from 20 kcal to 900 kcal, from 75 kcal to 700 kcal, from 150 kcal to 500 kcal, from 200 kcal to 450 kcal, or from 200 kcal to 400 kcal per serving.

[0040] As previously mentioned, the nutritional compositions according to the first, second, and third embodiments comprise at least one source of protein in an amount sufficient to provide 6 grams to 50 grams of protein per serving of the nutritional composition. In certain embodiments according to the first, second, and third embodiments, the nutritional composition comprises 6 grams to 50 grams of protein per serving, including 9 grams to 40 grams of protein, including 9 grams to 35 grams of protein, and also including 9 grams to 30 grams of protein per serving. In certain other embodiments according to the first, second, and third embodiments, the at least one source of protein comprises 5% to 40% of the nutritional composition, by weight, including from 10% to 30%>, and also including 15% to 25% by weight of the composition. Virtually any source of protein may be used so long as it is suitable for use in oral nutritional compositions and is otherwise compatible with any other selected ingredients or features in the nutritional composition. In certain embodiments according to the first, second, and third embodiments, the at least one source of protein may include a mixture of amino acids (often described as free amino acids) known for use in nutritional products, including the amino acids described herein, 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, or combinations thereof. [0041] The source of protein may include, but is not limited to, intact, hydro lyzed, 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, pea), and combinations thereof. Non-limiting examples of the source of protein include 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, and combinations thereof. In addition, the at least one source of protein in an amount sufficient to provide 6 grams to 50 grams of protein per serving may comprise any one source of protein or any combination of any of the various sources of protein provided in the non-limiting list presented above.

[0042] The nutritional composition, in certain embodiments according to the first, second, and third embodiments, further comprises at least one source of carbohydrates, or at least one source of fat, or combinations thereof. Therefore, in some embodiments the nutritional composition further comprises at least one source of carbohydrates, while in other embodiments the nutritional composition further comprises at least one source of fat, and yet in other embodiments the nutritional composition further comprises at least one source of carbohydrates and at least one source of fat.

[0043] As mentioned, in certain embodiments according to the first, second, and third embodiments, the nutritional composition further comprises at least one source of carbohydrates. In some embodiments according to the first, second, and third embodiments where the nutritional composition contains at least one source of carbohydrates, the at least one source of carbohydrates comprises from 10% to 80% of the nutritional composition, by weight, including from 30% to 60%, and also including from 50% to 70% by weight of the nutritional composition. In other embodiments according to the first, second, and third embodiments, the nutritional composition comprises 15 grams to 1 10 grams of at least one source of carbohydrates per serving. In other embodiments according to the first, second, and third embodiments, the nutritional composition comprises 25 grams to 90 grams of at least one source of carbohydrates per serving, including 40 grams to 65 grams of at least one source of carbohydrates per serving, and also including 45 grams to 55 grams of at least one source of carbohydrates per serving.

[0044] The at least one source of carbohydrates suitable for use in certain embodiments of the nutritional compositions disclosed herein may be simple, complex, or variations or combinations thereof. Generally, any source of carbohydrates may be used so long as it is suitable for use in oral 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 carbohydrates suitable for use in the nutritional compositions described herein include maltodextrin, hydrolyzed or modified starch or cornstarch, glucose polymers, corn syrup, corn syrup solids, rice-derived carbohydrates, sucrose, glucose, fructose, lactose, high fructose corn syrup, honey, sugar alcohols (e.g., maltitol, erythritol, sorbitol, etc.), isomaltulose, sucromalt, pullulan, potato starch, and other slowly-digested carbohydrates, 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, hydro xypropyl methylcellulose, tragacanth gum, karaya gum, gum acacia, chitosan, arabinoglactins, glucomannan, xanthan gum, alginate, pectin, low and high methoxy pectin, cereal beta-glucans (i.e., oat beta-glucan, barley beta- glucan), carrageenan and psyllium, digestion resistant maltodextrin (e.g., Fibersol™), other resistant starches, and combinations thereof.

[0045] In addition, in certain embodiments according to the first, second, and third embodiments, the nutritional composition further comprises at least one source of fat. In other embodiments according to the first, second, and third embodiments, the nutritional composition comprises no fat, or essentially no fat (i.e., less than 0.5 grams of fat per serving). In some embodiments according to the first, second, and third embodiments where the nutritional composition contains fat, the nutritional composition comprises from 2 grams to 45 grams of at least one source of fat per serving. In other embodiments according to the first, second, and third embodiments, the nutritional composition comprises from 5 grams to 35 grams of at least one source of fat per serving, including from 10 grams to 30 grams of at least one source of fat per serving, and also including from 15 grams to 25 grams of at least one source of fat per serving. In certain embodiments according to the first, second, and third embodiments where the nutritional composition comprises at least one source of fat, the at least one source of fat comprises from 5% to 30% of the nutritional composition, by weight, including from 10%> to 25% by weight of the nutritional composition, and also including from 12% to 18% by weight of the nutritional composition.

[0046] In general, any source of fat may be used so long as it is suitable for use in oral 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 safflower oil, MCT oil (medium chain triglycerides), sunflower oil, high oleic sunflower oil, palm and palm kernel oils, palm olein, canola oil, marine oils, cottonseed oils, eicosapentaenoic acid, docosahexaenoic acid, gamma- linolenic acid, conjugated linolenic acid from any source, and combinations thereof.

[0047] In certain embodiments according to the first, second, and third embodiments, the nutritional composition further comprises one or more functional ingredients that increase muscle protein synthesis, or decrease muscle protein degradation, or reduce muscle necrosis or apoptosis, or combinations thereof. For example, in certain embodiments according to the first, second, and third embodiments disclosed herein, the nutritional composition further comprises a functional ingredient selected from the group consisting of: β-hydroxy β-methylbutyrate (HMB); β-alanine; a green tea catechin selected from the group conisting of epigallocatechin gallate, epigallocatechin, epicatechin, catechin, epicatechin gallate, and metabolites thereof; lutein; creatine; carnitine; carnosine; a-ketoisocaproate; a-hydroxyisocaproic acid; taurine; arginine; anserine; a branched-chain amino acid selected from the group consisting of leucine, isoleucine, valine, metabolites of any of the foregoing branched-chain amino acids, and combinations thereof; methionine; cysteine; cystine; mushroom extract; cordycepic acid; spinach extract; arugula extract; broccoli extract; eggplant skin extract; plum extract; green tea extract; mixed green tea catechins; apple extract; ursolic acid; grape extract; resveratrol; olive extract; curcumin; a-tocopherol; vitamin D; and combinations thereof.

[0048] As mentioned, in certain embodiments according to the first, second, and third embodiments, the nutritional composition comprises β -hydroxy- β-methylbutyrate (HMB). As used herein the terms HMB and -hydroxy- -methylbutyrate should be understood to include multiple forms, including, but not limited to, salts, the free acid, esters, and lactones, unless it is clear from the context that only one form is meant. HMB is a metabolite of the essential amino acid leucine and has been shown to enhance muscle mass and muscle function. One suitable form of HMB that may be utilized is the calcium salt of HMB, also designated as Ca-HMB, which is most typically the monohydrate calcium salt. The HMB used can come from any source. Calcium HMB monohydrate is commercially available from Technical Sourcing International (TSI) of Salt Lake City, Utah. Note that all amounts of HMB described herein are based on use of Ca-HMB. When referring to amounts of HMB herein, the amounts are based on the assumption that the HMB is being provided as Ca-HMB, unless specifically indicated otherwise. Other suitable forms of HMB that may be utilized include, but are not limited to, free acid, salt, anhydrous salt, ester, lactone, or other product forms that provide a bioavailable form of HMB suitable for administration. Non-limiting examples of suitable salts of HMB (hydrated or anhydrous) for use herein include sodium, potassium, chromium, calcium, and other non-toxic salt forms.

[0049] In certain embodiments according to the first, second, and third embodiments, the nutritional composition comprises 0.4 grams to 4 grams of HMB per serving. For example, in certain embodiments according to the first, second, and third embodiments, the nutritional composition comprises 0.5 grams to 3.5 grams of HMB per serving, including 0.5 grams to 2.5 grams of HMB per serving, including 1 gram to 2 grams of HMB per serving, and also including 1 gram to 1.5 grams of HMB per serving. The nutritional composition may be administered as one serving per day, two servings per day, three servings per day, or four or more servings per day to receive a desired amount of HMB. In certain embodiments according to the first, second, and third embodiments, the nutritional composition comprises 1.5 grams of HMB per serving. In certain other embodiments according to the first, second, and third embodiments where the nutritional composition is a liquid, the concentration of HMB in the nutritional composition may range up to 10%, including from 0.01% to 10%>, including from 0.1 %> to 5.0%, including from 0.5% to 2%, and also including from 0.4% to 1.5% by weight of the nutritional composition.

[0050] As previously discussed, the nutritional composition, in certain embodiments according to the first, second, and third embodiments, may further comprise green tea extract. Green tea extract is a source of polyphenols, or green tea catechins, which function as antioxidants. Suitable green tea extracts used in certain embodiments of the nutritional compositions disclosed herein may contain polyphenols including epigallocatechin gallate ("EGCg"), 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; fiavonols such as kaempherol, quercetin, myricetin; condensed fiavanoids, and tannin glycosides. Generally, EGCg is the most abundant polyphenol present in green tea. Non- limiting examples of suitable green tea extracts include a liquid form with a high concentration of the polyphenols, a solid form (e.g., a powder), and mixtures thereof. In certain embodiments where green tea extract is utilized, the extract is decaffeinated such that it contains less than 1% by weight caffeine, or even less than 0.5% by weight caffeine.

[0051] In certain embodiments according to the first, second, and third embodiments, the nutritional composition comprises at least one source of EGCg in an amount sufficient to provide 10 milligrams to 1200 milligrams of EGCg per serving. In other embodiments according to the first, second, and third embodiments, the nutritional composition comprises at least one source of EGCg in an amount sufficient to provide 10 milligrams to 1000 milligrams of EGCg per serving, including 125 milligrams to 750 milligrams of EGCg per serving, including 125 milligrams to 500 milligrams of EGCg per serving, including 250 milligrams to 500 milligrams of EGCg per serving, including 60 milligrams to 375 milligrams of EGCg per serving, and also including 125 milligrams to 250 milligrams of EGCg per serving.

[0052] In certain embodiments according to the first, second, and third embodiments, where the source of EGCg is provided by a green tea extract, the green tea extract comprises 3% to 100%) by weight solids of EGCg. In certain other embodiments of the preceding embodiments, the green tea extract comprises 30%> to 100% by weight solids of EGCg, 45% to 100%) by weight solids of EGCg, and also including 90%> to 100%) by weight solids of EGCg.

[0053] In certain embodiments according to the first, second, and third embodiments, the nutritional composition includes EGCg from sources other than green tea-based sources. These sources include, but are not limited to, oolong tea-based sources such as oolong tea, oolong tea extracts, and the like; white tea-based sources such as white tea, white tea extracts, and the like; macha tea, macha tea extracts, and the like; yellow tea, yellow tea extracts, and the like; and dark tea (i.e., Chinese dark tea), dark tea extracts, and the like.

[0054] In certain embodiments according to the first, second, and third embodiments, the nutritional composition includes a functional ingredient that is an EGCg-related ingredient such as one or more of epigallocatechin gallate, epigallocatechin, epicatechin, catechin, or epicatechin gallate. Furthermore, in certain embodiments of the first, second, and third embodiments, the functional ingredient is an EGCg-related ingredient selected from the group consisting of epigallocatechin gallate, epigallocatechin, epicatechin, catechin, epicatechin gallate, or metabolites of any of the foregoing five green tea catechins. In certain embodiments of the first, second, and third embodiments, the EGCg-related ingredients (i.e., epigallocatechin gallate, epigallocatechin, epicatechin, catechin, epicatechin gallate) will be provided by a green tea extract.

[0055] In certain embodiments according to the first, second, and third embodiments, the nutritional composition comprises 10 milligrams to 1200 milligrams of green tea extract, mixed green tea catechins, one or more metabolites of a green tea catechin, and combinations thereof. The term "mixed green tea catechins" is used herein to refer to a combination of at least two green tea catechins (i.e., epigallocatechin gallate, catechin, epicatechin, gallocatechin, epigallocatechin, epicatechin gallate).

[0056] As previously mentioned, in certain embodiments according to the first, second, and third embodiments, the nutritional composition comprises β-alanine. β-alanine is a naturally occurring β amino acid that is the rate-limiting precursor of carnosine. Dietary supplementation with β-alanine has been shown to increase the concentration of carnosine in muscles, delay fatigue in athletes, and increase total muscular work done. In certain embodiments according to the first, second, and third embodiments, the nutritional composition comprises 0.1 grams to 10 grams of β-alanine per serving. In certain embodiments of the first, second, and third embodiments, the nutritional composition comprises 0.1 grams to 6 grams of β-alanine per serving, including 1 gram to 4 grams of β-alanine per serving, including 1 gram to 3.5 grams of β-alanine per serving, including 1 gram to 2 grams of β-alanine per serving, and also including 1.5 grams of β-alanine per serving. In certain embodiments where the nutritional composition contains β-alanine, the concentration of β-alanine in the nutritional composition may range from 0.1% to 5%, including from 0.1 % to 2%, including from 0.1 % to 1%, and also including from 0.1% to 0.5% by weight of the nutritional composition.

[0057] The β-alanine may be provided in various forms. For example, the β-alanine may be provided in free form or as a derivative (e.g., salt, ester, lactone, etc.). All amounts of β-alanine referred to herein refer to either free β-alanine or the β-alanine portion of the salt, ester, lactone, etc. Virtually any source of β-alanine is suitable for use in certain embodiments of the nutritional compositions described herein. In certain embodiments according to the first, second, and third embodiments, the β-alanine is free β-alanine. One suitable source of free beta-alanine is commercially available from Compounds Solutions (Escondido, California).

[0058] In accordance with certain embodiments of the first, second, and third embodiments, the nutritional composition is formulated as a clear liquid having a pH of 2 to 5, and also having no more than 0.5% fat by weight of the nutritional composition. The limited amount of fat contributes to the desired clarity and the desired pH of the nutritional composition. Typically, liquid nutritional compositions desired to be clear, or at least substantially translucent, are substantially free of fat. As used herein "substantially free of fat" refers to nutritional compositions containing less than 0.5%, and including less than 0.1% fat by weight of the total composition. "Substantially free of fat" also may refer to nutritional compositions disclosed herein that contain no fat, i.e., zero fat. Furthermore, embodiments of liquid nutritional compositions that have a desired acidic pH in the range of 2 to 5, e.g., juices, fruit juices, fruit- flavored beverages, etc. , typically are substantially free of fat. Liquid nutritional compositions that are both clear and have a pH ranging from 2 to 5 are also typically substantially free of fat. In certain of the preceding embodiments, the pH of the nutritional composition may be from 2.5 to 4.6, including a pH of 3 to 3.5. In those embodiments of the nutritional compositions that are substantially free of fat but have some amount of fat present, the fat may be present as a result of being inherently present in another ingredient (e.g., a source of protein) or may be present as a result of being added as one or more separate sources of fat.

[0059] In certain embodiments according to the first, second, and third embodiments disclosed herein, the nutritional composition may further comprise other optional components or ingredients that may modify the physical, chemical, aesthetic or processing characteristics of the nutritional composition or serve as pharmaceutical or additional nutritional components. Many such optional ingredients are known or otherwise suitable for use in medical food or other nutritional products or pharmaceutical dosage forms and may also be used in the nutritional compositions disclosed herein, provided that such optional ingredients are safe for oral administration and are compatible with the essential and other ingredients in the selected product form.

[0060] Non-limiting examples of such optional ingredients include preservatives, emulsifying agents, buffers, creatine, fructooligosaccharides, galactooligosaccharides, polydextrose, and other prebiotics, probiotics, pharmaceutical actives, anti-inflammatory agents, additional nutrients, colorants, flavors, thickening agents and stabilizers, emulsifying agents, lubricants, and so forth.

[0061] In certain embodiments according to the first, second, and third embodiments disclosed herein, the nutritional composition may further comprise at least one sweetening agent. In certain embodiments, the at least one sweetening agent is at least one sugar alcohol such as maltitol, erythritol, sorbitol, xylitol, mannitol, isolmalt, and lactitol, or at least one artificial or high potency sweetener such as acesulfame K, aspartame, sucralose, saccharin, stevia, and tagatose, and combinations thereof. The sweetening agents, especially as a combination of a sugar alcohol and an artificial sweetener, are especially useful in formulating liquid nutritional compositions having a desirable favor profile. These sweetener combinations are especially effective in masking undesirable flavors, for example, as sometimes associated with the addition of vegetable proteins to a liquid nutritional composition. In certain embodiments according to the first, second, and third embodiments disclosed herein, the nutritional composition may comprise at least one sugar alcohol with a concentration in a range from at least 0.01%, including from about 0.1% to about 10%>, and also including from about 1% to about 6%, by weight of the nutritional composition. In certain embodiments according to the first, second, and third embodiments disclosed herein, the nutritional composition may comprise at least one artificial sweetener with a concentration in a range from 0.01% to 5%, including from 0.05% to 3%, and also including from 0.1% to 1.0%, by weight of the nutritional composition. [0062] A flowing agent or anti-caking agent may be included in certain embodiments of the nutritional composition according to the first, second, and third embodiments disclosed herein to retard clumping or caking of a nutritional powder embodiment over time and to make the nutritional powder flow easily from its container. Any known flowing or anti-caking agents that are known or otherwise suitable for use in a nutritional powder or product form are suitable for use herein, non-limiting examples of which include tricalcium phosphate, silicates, and combinations thereof. The concentration of the flowing agent or anti-caking agent in certain embodiments of the nutritional composition according to the first, second, and third embodiments disclosed herein varies depending upon the product form, the other selected ingredients, the desired flow properties, and so forth, but most typically range from about 0.1% to about 4%, including from about 0.5% to about 2%, by weight of the nutritional composition.

[0063] In certain embodiments according to the first, second, and third embodiments disclosed herein, the nutritional composition may comprise a stabilizer. Any stabilizer that is known or otherwise suitable for use in a nutritional composition is also suitable for use herein, some non- limiting examples of which include gums such as xanthan gum. In certain embodiments according to the first, second, and third embodiments disclosed herein, the stabilizer may represent from about 0.1 % to about 5.0%, including from about 0.5%> to about 3%, including from about 0.7% to about 1.5%, by weight of the nutritional composition.

[0064] In certain other embodiments according to the first, second, and third embodiments disclosed herein, the nutritional composition may further comprise any of a variety of vitamins or related nutrients, non-limiting examples of which include vitamin A, vitamin E, vitamin D2, vitamin D3, vitamin A palmitate, vitamin E acetate, vitamin C palmitate (ascorbyl palmitate), vitamin K, thiamine, riboflavin, pyridoxine, vitamin Bi₂, carotenoids (e.g. , beta-carotene, zeaxanthin, lutein, lycopene), niacin, folic acid, pantothenic acid, biotin, vitamin C, choline, inositol, salts and derivatives thereof, and combinations thereof. In yet other embodiments according to the first, second, and third embodiments disclosed herein, the nutritional composition comprises any of a variety of additional minerals, non-limiting examples of which include calcium, selenium, potassium, iodine, phosphorus, magnesium, iron, zinc, manganese, copper, sodium, molybdenum, chromium, chloride, and combinations thereof. [0065] In certain embodiments according to the first, second, and third embodiments disclosed herein, the nutritional compositions optionally include one or more masking agents to reduce or otherwise obscure the development of any residual bitter flavors and after taste in the nutritional compositions over time. Suitable masking agents include natural and artificial sweeteners, sodium sources such as sodium chloride, and hydrocolloids, such as guar gum, xanthan gum, carrageenan, gellan gum, and combinations thereof. The amount of masking agent in certain embodiments of the nutritional composition may vary depending upon the particular masking agent selected, other ingredients in the formulation, and other formulation or product target variables. Such amounts, however, most typically range from 0.1% to 3%, including form 0.15% to 3%, and also including from 0.2% to 2.5%, by weight of the nutritional composition.

[0066] The various embodiments of the nutritional composition according to the first, second, and third embodiments disclosed herein may be prepared by any process or suitable method (now known or known in the future) for making a selected product form, such as a nutritional solid, a nutritional powder, or a nutritional liquid. Many such techniques are known for any given product form such as nutritional liquids or nutritional powders and can easily be applied by one of ordinary skill in the art to the various embodiments of the nutritional composition according to the first, second, and third embodiments disclosed herein.

[0067] In one suitable manufacturing process for liquid nutritional compositions, for example, 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., canola oil, corn oil, etc.) and then adding an emulsifier (e.g., lecithin), fat soluble vitamins, and a portion of the total protein (e.g., milk protein concentrate, etc.) 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, sodium citrate, etc.), trace and ultra trace minerals (TM/UTM premix), thickening or suspending agents (e.g., avicel, gellan, carrageenan). 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, potassium iodide, etc.), or carbohydrates (e.g., fructooligosaccharide, sucrose, corn syrup, etc.), or combinations thereof. The PIW slurry is then formed by mixing with heat and agitation the remaining protein. [0068] In accordance with this process, the three resulting slurries are blended together with heated agitation and the pH adjusted to the desired range, e.g., 6.6 to 7, after which the nutritional composition is subjected to high-temperature short-time (HTST) processing. The nutritional 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. At this point, the liquid nutritional composition may be packaged and sterilized according to any suitable sterilization technique, such as aseptic, retort, or hot-fill sterilization.

[0069] A nutritional solid, such as a spray dried nutritional powder or drymixed nutritional powder, may be prepared by any collection of known or otherwise effective technique, suitable for making and formulating a nutritional powder. For example, when the nutritional powder is a spray dried nutritional powder, the spray drying step may likewise include any spray drying technique that is known for or otherwise 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.

[0070] One method of preparing the spray dried nutritional powder comprises forming and homogenizing an aqueous slurry or liquid comprising predigested fat, and optionally protein, carbohydrate, and other sources of fat, and then spray drying the slurry or liquid to produce a spray dried nutritional powder. The method may further comprise the step of spray drying, drymixing, or otherwise adding additional nutritional or functional ingredients, including any one or more of the ingredients described herein, to the spray dried nutritional powder.

[0071] Other suitable methods for making nutritional products are described, for example, in U.S. Pat. No. 6,365,218 (Borschel, et al), U.S. Pat. No. 6,589,576 (Borschel, et al), U.S. Pat. No. 6,306,908 (Carlson, et al), U.S. Pat. Appl. No. 20030118703 Al (Nguyen, et al), which descriptions are incorporated herein by reference to the extent that they are consistent herewith.

[0072] As previously mentioned, the methods according the first, second, and third embodiments disclosed herein employ the combination of providing, or administering, to the subject a nutritional composition {e.g., any one or more of the various embodiments of nutritional compositions described herein), and applying to the subject a vibrational stimulus having a frequency of 10 Hz to 120 Hz and an amplitude of 0.1 g to 20 g, where 1 g is equal to Earth's gravitational field, or 9.8 m/s . The combination of administering to the subject a nutritional composition as described herein, and applying to the subject a vibrational stimulus as described herein enhances the beneficial effects provided by either feature individually.

[0073] In certain embodiments according to the first, second, and third embodiments, the subject is a human. In certain other embodiments according to the first, second, and third embodiments, the subject is elderly. In certain embodiments according to the first, second, and third embodiments, the subject is a subject in need of motor function enhancement, functional status enhancement, or muscle strength enhancement by virtue of having sarcopenia, cachexia, or a subject who is bedridden or otherwise immobile and suffers from muscle disuse. Sarcopenia is generally defined as the age-related loss of muscle mass, strength and function. In general, sarcopenia appears to begin in the fourth decade of life and accelerates after the age of approximately 75 years. Cachexia is typically defined as general physical wasting and malnutrition usually associated with chronic disease. Symptoms of cachexia include loss of weight, muscle atrophy, fatigue, weakness, and significant loss of appetite. In certain embodiments according to the first, second, and third embodiments, the subject is a subject having or at risk of having one or more of reduced motor function, reduced functional status, or muscle weakness by virtue of normal aging, sarcopenia, cachexia, inactivity, immobility, or combinations thereof.

[0074] The vibrational stimulus applied to the subject may be provided in a variety of effective ways. For example, in certain embodiments according to the first, second, and third embodiments, the vibrational stimulus applied to the subject is whole body vibration. As used herein, "whole body vibration" refers to mechanical oscillations that are transferred to the entire body of a subject, typically through a body support system, such as a vibrating platform. A number of apparatuses are commercially available and suitable for use in the methods disclosed herein. For example, the LIV™ Tablet (available from Marodyne LLC of Lakeland, Florida), the VibraFlex^® 600 platform (available from Orthometrix, Inc. of Naples, Florida), the Power Plate^® machine (available from Power Plate North America, Inc. of Irvine, California), and the VibraSlim EUROplate^® machine (available from VibraSlim Fitness USA of Los Angeles, California) are all commercially available vibration apparatuses that impart linear vibration (i.e., the platform, at all times, remains parallel to the ground and undergoes vertical displacement) or oscillating vibration (i.e. , the platform undergoes vertical displacement by tilting, or pivoting, about a horizontal axis) to the body. However, it will be appreciated that virtually any source of vibrational stimulus, including any type or direction of vibration, may be utilized in performing the methods disclosed herein.

[0075] In certain other embodiments according to the first, second, and third embodiments, the vibrational stimulus is applied directly to at least one target area of the subject. The term "target area" as used herein refers to an area (e.g. , a specific muscle or group of muscles) of the subject's body in need of muscle function enhancement, or an area of the subject's body for which muscle function enhancement is desired. In certain embodiments, the target area of the subject comprises one of the limbs, the trunk, or the spine of the subject. For example, a source of vibrational stimulus (e.g., a handheld vibrating device that achieves the required frequency and amplitude) may be placed directly on the subject's quadriceps, as opposed to indirect application of the vibrational stimulus to the subject's quadriceps through whole body vibration.

[0076] The vibrational stimulus applied to the subject can have varying frequencies and amplitudes. For example, in certain embodiments according to the first, second, and third embodiments, the vibrational stimulus has a frequency of 30 Hz to 50 Hz and an amplitude of 5 g to 20 g. In certain other embodiments according to the first, second, and third embodiments, the vibrational stimulus has a frequency of 30 Hz to 90 Hz and an amplitude of 0.1 g to 1 g. A low intensity vibrational stimulus (e.g. , frequency of 30-90 Hz and amplitude of 0.1-1 g) is particularly suited for elderly subjects as it is generally considered to be safer since less force is being applied to the subject. On the other hand, a high intensity vibrational stimulus (e.g,. 30-50 Hz and amplitude of 5-20 g) that applies higher forces may be desirable for non-elderly subjects desiring muscle function or power enhancements. The particular frequency and amplitude of the vibrational stimulus applied to the subject can be selected in accordance with the subject's physical condition, or according to the judgment of an appropriate practitioner.

[0077] In certain embodiments according to the first, second, and third embodiments, the vibrational stimulus may be applied in the context of "vibration training," which utilizes a defined frequency and amplitude of periodic oscillation in connection with a specific exercise or activity protocol. Simple acts of holding a certain posture on a vibrating platform account for a low-intensity activity protocol.

[0078] In general, the vibrational stimulus is applied to the subject repetitively for varying amounts of time. For example, in certain embodiments according to the first, second, and third embodiments, the vibrational stimulus is applied to the subject in one to ten repetitions, and each repetition ranges from 0.5 seconds to 60 minutes. In certain other embodiments according to the first, second, and third embodiments, the vibrational stimulus is applied to the subject in one to ten repetitions, and each repetition ranges from 10 minutes to 60 minutes, including from 10 minutes to 55 minutes, including from 10 minutes to 50 minutes, including from 10 minutes to 45 minutes, including from 10 minutes to 30 minutes, including from 10 minutes to 20 minutes, and also including from 10 minutes to 15 minutes. In certain other embodiments according to the first, second, and third embodiments, the vibrational stimulus is applied to the subject in one to ten repetitions, and each repetition ranges from 0.5 seconds to 15 minutes. In certain other embodiments, according to the first, second, and third embodiments, the vibrational stimulus is applied to the subject in one to ten repetitions, and each repetition ranges from 0.5 seconds to 5 minutes, including from 1 second to 2 minutes, including from 5 seconds to 1 minutes, including from 10 seconds to 40 seconds, and also including from 20 seconds to 30 seconds. In certain other embodiments according to the first, second, and third embodiments, the vibrational stimulus is applied to the subject in one to ten repetitions, and each repetition ranges from 0.5 seconds to 5 minutes, including from 1 second to 2 minutes, including from 5 seconds to 1 minutes, including from 10 seconds to 40 seconds, and also including from 20 seconds to 30 seconds.

[0079] In certain embodiments according to the first, second, and third embodiments, each repetition of vibrational stimulus is followed by a rest interval where no vibrational stimulus is applied. In certain embodiments, the rest interval ranges from 1 second to 5 minutes. As used herein, the phrase "rest interval" refers to a period of time where no vibrational stimulus is applied that occurs between repetitions of vibrational stimulus. Thus, if only a single repetition of vibrational stimulus is applied, then there is no corresponding rest interval. If three repetitions of vibrational stimulus are applied, then there will be two rest intervals: a first rest interval between the first and second repetition, and a second rest interval between the second and third repetition. The term "session," as used herein, unless otherwise indicated, refers to a single repetition of the vibrational stimulus, as well as the combined repetitions of vibrational stimulus and rest intervals. In an exemplary embodiment, a session comprises applying the vibrational stimulus to the subject in 5 repetitions lasting 1 minute each with a 30 second rest interval between each repetition.

[0080] In certain embodiments according to the first, second, and third embodiments, the vibrational stimulus may be applied to the subject in 1 to 5 sessions per day, including 1 to 3 sessions per day, and also including 1 to 2 sessions per day. In certain embodiments, the vibrational stimulus is applied to the subject one day per week, two days per week, three days per week, four days per week, five days per week, six days per week, or daily. In certain embodiments, the vibrational stimulus is applied 3 to 5 days per week. Moreover, the vibrational stimulus can be applied to the subject over any period of days, weeks, months, or years. For example, in certain embodiments according to the first, second, and third embodiments, the vibrational stimulus is applied to the subject for a period of 2 weeks to 12 weeks, including 4 weeks to 8 weeks, and also including 6 weeks. In an exemplary embodiment, the vibrational stimulus is applied to the subject in 48 sessions over a 12 week period, where each session comprises applying the vibrational stimulus to the subject in 10 repetitions lasting 2 minutes each with a 1 minute rest interval between each repetition.

[0081] In general, the steps of providing a nutritional composition and applying a vibrational stimulus can be accomplished separately or concurrently. In certain embodiments according to the first, second, and third embodiments, the nutritional composition is provided to the subject prior to, concurrent with, or subsequent to the application of the vibrational stimulus, and vice versa. For example, in certain embodiments according to the first, second, and third embodiments, the nutritional composition is provided to the subject prior to the application of the vibrational stimulus (e.g., within 2 hours before applying the vibrational stimulus). In other words, the subject consumes the nutritional composition before the vibrational stimulus is applied to the subject, which in certain instances may occur between repetitions of the vibrational stimulus (i.e., during a rest interval), between sessions of vibrational stimulus, or combinations thereof. In certain other embodiments according to the first, second, and third embodiments, the nutritional composition is provided to the subject after application of the vibrational stimulus (e.g., within 2 hours after applying the vibrational stimulus). For example, the subject consumes the nutritional composition subsequent to the application of the vibrational stimulus, which in certain instances may occur between repetitions of the vibrational stimulus (i.e., during a rest interval), between sessions of vibrational stimulus, or combinations thereof.

[0082] As previously mentioned, the components of motor function include muscle strength, motor coordination, balance, reflexes, and speed. Thus, if any individual component of muscle strength, motor coordination, balance, reflexes, or speed is enhanced, then motor function is necessarily enhanced. Moreover, enhancement of two or more components of muscle strength, motor coordination, balance, reflexes, or speed may further, but not necessarily, enhance motor function beyond enhancements observed with any single component.

[0083] Motor function is also influenced by vestibular, visual, and proprioceptive processes that contribute to balance and reflexes. The vestibular system is a spatial sensory system that registers rotational forces and linear accelerations within specialized structures of the inner ear. The forces and accelerations are integrated and relayed to: (1) neurons that control eye movement to maintain clear vision; and (2) to muscular systems to keep a subject upright. Proprioception is the sense of one's body parts' spatial orientation, movement, effort, and force with respect to one's other body parts. Proprioception may be mediated by mechanical and electrical receptors in the muscle, tendons, joints, or skin. Proprioception is a critical factor for the ability to stably stand, and both deteriorate with age. Moreover, increased risk of slip and slip-induced falls may occur in a subject due to normal aging, inactivity, or disease-related disorders. Sufficient balance and reflexes are necessary to counteract slip-induced fall forces. In such cases, vestibular, visual, and proprioceptive responses are also important to counteract falls.

[0084] Motor function may be evaluated by a wide variety of methods. For example, motor function can be assessed by measurement of the following: self-selected or usual walking gait speed, where gait speed is the distance traveled divided by the ambulation time; maximum walking gait speed; step length wherein step length is the perpendicular distance between the heel of one foot-strike to the heel of the next foot-strike of the opposite foot; step time wherein step time is the time elapsed from floor contact of one foot to floor contact of the next foot; stride length wherein stride length is the perpendicular distance between the heel of one foot-strike to the heel of the next foot-strike of the same foot; stride time; base width wherein base width is the perpendicular distance from the heel of one foot-strike to the line of progression between two foot-strikes of the opposite foot; step width; stride width; gait cycling time; stance time; swing time; double support phase wherein double support phase is the phase of the gait cycle when both feet are in contact with the ground; gait parameters measured on an inclined plane, declined plane, or throughout progressively increased velocity on a treadmill; intraindividual variability for gait measures; chair rise test wherein the amount of time to complete 5 chair rises is measured; Katz Index of Independence in Activities of Daily Living; Palliative Performance Scale; Tinetti Gait and Balance Scale; Star Excursion Balance Test; tandem standing and tandem walking to measure balance; single-leg dynamic postural sway on a force plate; single-leg stance time on a hard surface; single-leg stance time on a balance pad; manual muscle testing; isokinetic or isometric measurements of muscle strength including knee extension-flexion or plantar flexion; one-repetition maximum strength; maximum rate of force development; electromyography (EMG) of muscle; median activation frequency determined by EMG of soleus and gastrocnemius medialis during plantar-flexion; mean amplitude voltage determined by EMG of muscle; EMG of muscle before or after activity; EMG during stance perturbation, training or jumping; nerve stimulation twitch response of the soleus and gastrocnemius muscle; reflex activity during flexion; Hoffman's reflex (H-reflex) or other mechanical stretch reflex; H-reflex measured during 2 tasks such as plantar flexion and stance perturbation; Berg Balance Scale; Short Physical Performance Battery; mechanography; jump height; twenty-meter sprint performance; ten yard sprint performance; forty yard sprint performance; countermovement jump power; bounce-drop jump power; and vertical impact force before jumping. The amount of enhancement in motor function can be determined by comparing the motor function of subjects prior to practicing the methods disclosed herein and subsequent to practicing the methods disclosed herein.

[0085] Muscle weakness contributes to a decline or reduction in motor function. Muscle weakness may occur in a subject due to normal aging, inactivity, or disease-related disorders, and may have a negative impact on the overall health and well-being of the subject. Typically, whole muscle group strength is regulated by two separate pathways: (1) muscle hypertrophy, or pathways that regulate the size of muscle, where muscle size is the net effect of (a) total muscle protein synthesis, and (b) total muscle protein degradation; and (2) excitation-contraction coupling (EC coupling), or pathways that intrinsically modulate the amplitude of the response to synaptic neuromuscular stimulation, regardless of muscle size. Together, decreased hypertrophic responses and dysfunctional EC coupling, or increased EC uncoupling, generally accelerate and promote rapid loss of muscle strength. Thus, inhibiting or preventing each pathway, individually or together, will mitigate muscle weakness.

[0086] Neuronal atrophy or degeneration may also contribute to a decline or reduction in motor function, functional status, and muscle weakness. Neuronal atrophy may occur in a subject due to normal aging, inactivity, or disease-related disorders. In addition, motor neuron wasting may lead to muscle atrophy, weakness, and ultimately reduce motor coordination in a subject. As mentioned above, a chronic decline in motor coordination may occur in a subject and ultimately lead to a reduction in functional status.

[0087] In certain embodiments according to the first, second, and third embodiments, the enhanced motor function, enhanced functional status, or mitigation of muscle weakness is caused by one or more of enhanced muscle function, an increase in muscle protein synthesis, a reduction of muscle necrosis or apoptosis, enhanced motor coordination, enhanced balance, enhanced sensorimotor reactivity of myofibers or muscle groups that contribute to reflexes, and enhanced speed. The application of vibrational stimulus promotes stimulation of sensory receptors (e.g., muscle spindles), which can lead to repetitive muscle contractions. These muscle contractions can increase blood perfusion and capillary density, which can improve delivery of the various ingredients of the nutritional compositions disclosed herein. For example, and as previously described, in certain embodiments the nutritional composition comprises one or more functional ingredients that increase muscle protein synthesis, or decrease muscle protein degradation, or reduce muscle necrosis or apoptosis, or combinations thereof (e.g., protein, HMB, EGCg, amino acids, β-alanine, etc.).

[0088] Various embodiments of the methods disclosed herein include enhancing motor function, enhancing functional status, or enhancing muscle strength (i.e., mitigating muscle weakness) in a subject. The terms "enhancing," "enhancement," or "enhanced" when used in connection with the attributes of motor function, functional status, or muscle strength refers to an increase in the attribute, or alternatively, the maintenance of the attribute. For example, in an exemplary embodiment according to the first, second, and third embodiments, providing to the subject a nutritional composition as previously described and applying to the subject a vibrational stimulus as previously described can increase the subject's muscle strength by 10%, and accordingly can enhance motor function, enhance functional status, and mitigate muscle weakness. In certain embodiments according to the first embodiment, motor function can be enhanced by 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or 100%. In certain embodiments according to the second embodiment, functional status can be enhanced by 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or 100%. In certain embodiments according to the third embodiment, muscle strength can be enhanced (i.e., muscle weakness can be mitigated) by 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or 100%.

[0089] As noted above, enhancing an attribute (i.e., motor function, functional status, muscle strength) also refers to the maintenance of the attribute. In this context, maintenance of an attribute refers to retaining an amount of the attribute that corresponds to the measurement of the attribute of the subject prior to practicing the methods disclosed herein, or a percentage thereof. Accordingly, in various embodiments, providing to the subject a nutritional composition as described herein and applying to the subject a vibrational stimulus as described herein can be used to maintain 100% of the motor function, functional status, or muscle strength of the subject, or in other embodiments lesser amounts. For example, in certain embodiments of the first embodiment, the method can maintain 50% motor function, 60% motor function, 70% motor function, 80% motor function, 90% motor function, 95% motor function, or any amounts ranging from 50% to 100%. In certain embodiments of the second embodiment, the method can maintain 50% of the functional status, 60% of the functional status, 70% of the functional status, 80% of the functional status, 90% of the functional status, 95% of the functional status, or any amounts ranging from 50% to 100%. In certain embodiments of the third embodiment, the method can maintain 50%> muscle strength, 60%> muscle strength, 70%> muscle strength, 80%> muscle strength, 90%> muscle strength, 95% muscle strength, or any amounts ranging from 50%> to 100%. EXAMPLES

[0090] The following examples illustrate certain embodiments or features of methods and nutritional compositions according to the first, second, and third embodiments disclosed herein. The examples are given solely for the purpose of illustration and are not to be construed as limitations of the present disclosure, as many variations thereof are possible without departing from the spirit and scope of the disclosure. All exemplified amounts are weight percentages based upon the total weight of the composition, unless otherwise specified.

EXAMPLE 1

[0091] Examples 1 illustrates certain embodiments of methods according to the first, second, and third embodiments disclosed herein. A subject is 70 years of age and is diagnosed as having sarcopenia. An initial handgrip strength assessment is performed on the subject to establish a baseline muscle strength. The handgrip strength is measured with a hand-held dynamometer using the subject's dominant arm. The hand-held dynamometer is standardized and adjusted to the second joint of the finger just below the handle, with the arm adducted at their side and a 90- degree flexion at the elbow. The subject squeezes the dynamometer as forcefully as possible for three to five seconds. The force is measured in kilograms. The subject completes three trials and the average is used as the final strength value. In this example, the subject has a baseline handgrip strength of 25 kg.

[0092] The subject begins an 8 week program that includes consuming a nutritional composition and the application of vibrational stimulus to the subject's whole body (i.e., whole body vibration). On five days each week, the subject completely consumes a 10 fi. oz. serving of a liquid nutritional product containing 9 g of protein within 1 hour prior to the application of the vibrational stimulus. An exemplary liquid nutritional product formulation is listed in Table 1 below. The vibrational stimulus is applied to the subject in one session per day, the session includes applying the vibrational stimulus to the subject in 5 repetitions lasting 5 minutes each with a 30 second rest interval between each repetition. The vibrational stimulus has a frequency of 90 Hz and an amplitude of 0.2 g. During the 8 week program, the subject maintains their customary dietary and exercise regimen. Table 1

INGREDIENTS Amount (kg/1000 kg)

Water Quantity Sufficient

Sucrose 50.7

Corn syrup solids 61.3

Acidified Whey Protein Isolate 35.7

Citric Acid 2.00

Flavoring 2.00

Ascorbic Acid 0.535

Liquid Sucralose (25%) 0.275

Ultra Trace Mineral/Trace Mineral Premix¹ 0.230

Vitamin Premix 0.219

Acesulfame Potassium 0.110

Antifoam processing aid (non-silicone) 0.060

Coloring 0.0589

Natural and Artificial Flavor 2.0

Folic Acid 0.0013

Potassium Iodide 0.000204

¹ Ultra trace mineral/trace mineral premix includes one or more of the following: zinc sulfate, monohydrate; ferrous sulfate, dried; citric acid, anhydrous; manganese sulfate, monohydrate; copper sulfate, pentahydrate; chromium chloride, hexahydrate; sodium molybdate, dihydrate; sodium selenate, anhydrous; etc.

² Vitamin premix includes one or more of the following: dl-Alpha-Tocopheryl Acetate; Vitamin A Palmitate; Phylloquinone; Vitamin D3; Niacinamide; d-Calcium Pantothenate; Thiamine Chloride Hydrochloride; Pyridoxine Hydrochloride; Riboflavin; Folic Acid; Biotin; Cyanocobalamin; etc.

[0093] After conclusion of the 8 week program, the subject's handgrip strength is assessed according to the same protocol as described above. The handgrip strength assessment indicates that the subject has a post-program handgrip strength of 45 kg. Thus, the subject's muscle strength, as indicated by handgrip strength, is enhanced by 80%.

EXAMPLE 2

[0094] Examples 2 illustrates certain embodiments of methods according to the first, second, and third embodiments disclosed herein. An elderly subject, 80 years of age, is diagnosed as having muscle atrophy, which affects the subject's motor function. An initial muscle mass assessment is performed on the subject to establish a baseline muscle mass. The muscle mass is determined via the 24-hr urinary creatinine method. In this example, the subject has a baseline muscle mass of 15 kg, as determined by the 24-hr urinary creatinine method. [0095] The subject begins a 12 week program that includes consuming a nutritional composition and the application of vibrational stimulus to the subject's whole body (i.e., whole body vibration). On four days each week, the subject completely consumes an 8 fl. oz. serving of a liquid nutritional product containing 20 g of protein within 1 hour prior to the application of the vibrational stimulus. The nutritional information of an exemplary liquid nutritional product is listed in Table 2 below, with the specific ingredients provided immediately thereafter. The vibrational stimulus is applied to the subject in one session per day, the session includes applying the vibrational stimulus to the subject in 10 repetitions lasting 2 minutes each with a 15 second rest interval between each repetition. The vibrational stimulus has a frequency of 30 Hz and an amplitude of 1 g. During the 12 week program, the subject maintains their customary dietary and exercise regimen.

[0096] The exemplary liquid nutritional product of Table 2 includes the following ingredients: water, corn syrup, sucrose, milk protein concentrate, sodium caseinate, canola oil, corn oil, fructooligosaccharides, soy protein isolate, calcium beta-hydroxy-beta-methylbutyrate, whey protein concentrate, potassium citrate, natural and artificial flavors, potassium phosphate, lecithin, cellulose gel, magnesium hydroxide, calcium carbonate, ascorbic acid, calcium phosphate, choline chloride, sodium chloride, sodium phosphate, potassium hydroxide, zinc sulfate, cellulose cum, L-carnitine, carrageenan, dl-alpha-tocopherol acetate, dextrose, ferrous sulfate, maltodextrin, niacinamide, gellan gum, calcium pantothenate, citric acid, cupric sulfate, manganese sulfate, chromium chloride, thiamine chloride hydrochloride, coconut oil, vitamin A palmitate, pyridoxine hydrochloride, riboflavin, folic acid, biotin, sodium selenate, sodium molybdate, potassium iodide, phylloquinone, cyanocobalamin, and vitamin D3.

[0097] After conclusion of the 12 week program, the subject's muscle mass is assessed according to the same protocol as described above. The muscle mass assessment indicates that the subject has a post-program muscle mass of 18 kg. Thus, the subject's muscle mass is enhanced by 20% and muscle atrophy has been treated and prevented, which enhances the subject's motor function.

EXAMPLE 3

[0098] Examples 3 illustrates certain embodiments of methods according to the first, second, and third embodiments disclosed herein. An elderly subject, 75 years of age, is diagnosed as having sarcopenia. An initial handgrip strength assessment is performed on the subject to establish a baseline muscle strength. The handgrip strength is measured with a hand-held dynamometer using the subject's dominant arm. The hand-held dynamometer is standardized and adjusted to the second joint of the finger just below the handle, with the arm adducted at their side and a 90-degree flexion at the elbow. The subject squeezes the dynamometer as forcefully as possible for three to five seconds. The force is measured in kilograms. The subject completes three trials and the average is used as the final strength value. In this example, the subject has a baseline handgrip strength of 30 kg.

[0099] The subject begins an 8 week program that includes consuming a nutritional composition and the application of vibrational stimulus to the subject's whole body (i.e., whole body vibration). On five days each week, the subject completely consumes a 10 fi. oz. serving of a liquid nutritional product containing 9 g of protein within 1 hour prior to the application of the vibrational stimulus. An exemplary liquid nutritional product formulation is listed in Table 1 above. The vibrational stimulus is applied to the subject in one session per day, the session includes applying the vibrational stimulus to the subject in 1 repetition lasting 15 minutes. The vibrational stimulus has a frequency of 50 Hz and an amplitude of 0.1 g. During the 8 week program, the subject maintains their customary dietary and exercise regimen.

[00100] After conclusion of the 8 week program, the subject's handgrip strength is assessed according to the same protocol as described above. The handgrip strength assessment indicates that the subject has a post-program handgrip strength of 50 kg. Thus, the subject's muscle strength, as indicated by handgrip strength, is enhanced by 67%.

EXAMPLE 4

[00101] Examples 4 illustrates certain embodiments of methods according to the first, second, and third embodiments disclosed herein. An elderly subject, 80 years of age, is diagnosed as having sarcopenia. An initial usual walking speed and gait measures assessment is performed on the subject to establish a baseline gait speed. Gait speed is measured over a 10 meter course. Base width is measured using the GAITRite™ (CIR Systems, PA) electronic walkway (488 x 61 cm mat) and computerized gait analysis system. Gait speed is the distance traveled, 10 meters, divided by ambulation time and measured in centimeters per second. Base width, a measure of balance, is the perpendicular distance between the heel of one foot-strike and the line of progression between the heels of two consecutive foot-strikes of the opposite foot, and is measured in centimeters. A decrease in base width indicates an improvement in balance. The subject performs five short walks over the 10 meter course with the beginning and end of each walk traversed over the electronic treadmill, and the values for gait speed and base width are averaged. In this example, the subject has a baseline gait speed of 82 cm/s and a baseline base width of 11.2 cm.

[00102] The subject begins an 8 week program that includes consuming a nutritional composition and the application of vibrational stimulus to the subject's whole body (i.e., whole body vibration). On five days each week, the subject completely consumes a 10 fi. oz. serving of a liquid nutritional product containing 9 g of protein within 1 hour prior to the application of the vibrational stimulus. An exemplary liquid nutritional product formulation is listed in Table 1 above. The vibrational stimulus is applied to the subject in one session per day, the session includes applying the vibrational stimulus to the subject in 1 repetition lasting 30 minutes. The vibrational stimulus has a frequency of 35 Hz and an amplitude of 0.1 g. During the 8 week program, the subject maintains their customary dietary and exercise regimen.

[00103] After conclusion of the 8 week program, the subject's gait speed and base width are assessed according to the same protocol as described above. Gait analysis indicates that the subject has a post-program usual gait speed of 112 cm/s and post-program base width of 10.5 cm. Thus, the subject's walking speed, as indicated by usual gait speed assessment, is enhanced by 37%, and the subject's balance, as indicated by base width analysis, is enhanced 7%.

[00104] To the extent that the term "includes" or "including" is used in the specification or the claims, it is 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. See Bryan A. Garner, A Dictionary of Modern Legal Usage 624 (2d. Ed. 1995). Also, to the extent that the terms "in" or "into" are used in the specification or the claims, it is intended to additionally mean "on" or "onto." Furthermore, to the extent the term "connect" is used in the specification or claims, it is intended to mean not only "directly connected to," but also "indirectly connected to" such as connected through another component or components.

[00105] While the present application has been illustrated by the description of embodiments thereof, and while the 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 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 compositions and processes, and illustrative examples shown and described. Accordingly, departures may be made from such details without departing from the spirit or scope of the applicant's general inventive concept.

Claims

WHAT IS CLAIMED IS:

1. A method for enhancing motor function in a subject comprising:

a) providing to the subject a nutritional composition comprising at least one source of protein in an amount sufficient to provide 6 grams to 50 grams of protein per serving; and

b) applying to the subject a vibrational stimulus having a frequency of 10 Hz to 120 Hz and an amplitude of 0.1 g to 20 g;

whereby consumption of the nutritional composition and application of the vibrational stimulus result in enhanced motor function.

2. The method according to claim 1, wherein the at least one source of protein is selected from the group consisting of 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, and combinations thereof.

3. The method according to claim 1, wherein the nutritional composition further comprises 0.4 grams to 4 grams of β-hydroxy β-methylbutyrate per serving.

4. The method according to any one of claims 1-3, wherein the nutritional composition further comprises a functional ingredient selected from the group consisting of β-alanine;

epigallocatechin gallate, epigallocatechin, epicatechin, catechin, epicatechin gallate, and metabolites thereof; lutein; creatine; carnitine; carnosine; a-ketoisocaproate; a- hydroxyisocaproic acid; taurine; arginine; anserine; a branched-chain amino acid selected from the group consisting of leucine, isoleucine, valine, metabolites of any of the foregoing branched- chain amino acids, and combinations thereof; methionine; cysteine; cystine; mushroom extract; cordycepic acid; spinach extract; arugula extract; broccoli extract; eggplant skin extract; plum extract; green tea extract; mixed green tea catechins; apple extract; ursolic acid; grape extract; resveratrol; olive extract; curcumin; a-tocopherol; vitamin D; and combinations thereof.

5. The method according to any one of claims 1-3, wherein the nutritional composition further comprises at least one source of carbohydrate, or at least one source of fat, or combinations thereof.

6. The method according to any one of claims 1-3, wherein the nutritional composition is provided as a liquid and the serving is from 150 milliliters to 500 milliliters, and wherein 1 serving to 14 servings of the nutritional composition is administered to the subject per week.

7. The method according to claim 4, wherein the nutritional composition comprises 10 milligrams to 1200 milligrams of epigallocatechin gallate per serving.

8 The method according to claim 7, wherein the epigallocatechin gallate is provided by a green tea extract comprising from 3 weight % to 100 weight % of epigallocatechin gallate.

9. The method according to claim 4, wherein the nutritional composition comprises 10 milligrams to 1200 milligrams of green tea extract, mixed green tea catechins, one or more metabolites of a green tea catechin, and combinations thereof per serving.

10. The method according to claim 4, wherein the nutritional composition comprises 0.1 grams to 10 grams of β-alanine per serving.

11. The method according to claim 5, wherein the nutritional composition is a clear liquid having a pH of 2-5 and having no more than 0.5% fat by weight of the nutritional composition.

12. The method according to any one of claims 1-3, wherein the vibrational stimulus has a frequency of 30 Hz to 50 Hz and an amplitude of 5 g to 20 g.

13. The method according to claim 12, wherein the vibrational stimulus is applied to the subject in one to ten repetitions per day, wherein each repetition ranges from 0.5 seconds to 5 minutes.

14. The method according to claim 13, wherein each repetition is followed by a rest interval where no vibrational stimulus is applied, and the rest interval ranges from 1 second to 5 minutes.

15. The method according to any one of claims 1-3, wherein the vibrational stimulus has a frequency of 30 Hz to 90 Hz and an amplitude of 0.1 g to 1 g.

16. The method according to claim 15, wherein the vibrational stimulus is applied to the subject in one to ten repetitions per day, wherein each repetition ranges from 0.5 seconds to 15 minutes.

17. The method according to claim 16, wherein each repetition is followed by a rest interval where no vibrational stimulus is applied, and the rest interval ranges from 1 second to 5 minutes.

18. The method according to claim 15, wherein the vibrational stimulus is applied to the subject in one repetition per day, wherein the repetition ranges from 10 minutes to 60 minutes.

19. The method according to any one of claims 1-3, wherein the nutritional composition is provided to the subject prior to the application of the vibrational stimulus.

20. The method according to any one of claims 1-3, wherein the nutritional composition is provided to the subject after application of the vibrational stimulus.

21. The method according to any one of claims 1-3, wherein the vibrational stimulus is applied directly to at least one target area of the subject.

22. The method according to any one of claims 1-3, wherein the vibrational stimulus is whole body vibration.

23. The method according to any one of claims 1-3, wherein the subject is elderly.

24. The method according to any one of claims 1-3, wherein the subject is a human.

25. The method according to any one of claims 1-3, wherein the enhanced motor function is caused by one or more of enhanced muscle function, an increase in muscle protein synthesis, a reduction of muscle necrosis or apoptosis, enhanced motor coordination, enhanced balance, enhanced sensorimotor reactivity of myofibers or muscle groups that contribute to reflexes, and enhanced speed.

26. A method for enhancing the functional status of a subject, the method comprising:

a) providing a nutritional composition to a subject having or at risk of having reduced functional status, wherein the nutritional composition comprises at least one source of protein in an amount sufficient to provide 6 grams to 50 grams of protein per serving; and

b) applying to the subject a vibrational stimulus having a frequency of 10 Hz to 120 Hz and an amplitude of 0.1 g to 20 g to the subject;

whereby consumption of the nutritional composition and application of the vibrational stimulus result in enhanced functional status.

27. The method according to claim 26, wherein the at least one source of protein is selected from the group consisting of whey protein concentrate, whey protein isolate, whey protein hydrolysate, acid casein, sodium caseinate, calcium caseinate, potassium caseinate, casein hydrolysate, milk protein concentrate, milk protein isolate, milk protein hydrolysate, nonfat dry milk, condensed skim milk, soy protein concentrate, soy protein isolate, soy protein hydrolysate, pea protein concentrate, pea protein isolate, pea protein hydrolysate, collagen protein, and combinations thereof.

28. The method according to claim 26, wherein the nutritional composition further comprises 0.4 grams to 4 grams of β-hydroxy β-methylbutyrate per serving.

29. The method according to any one of claims 26-28, wherein the vibrational stimulus has a frequency of 30 Hz to 50 Hz and an amplitude of 5 g to 20 g.

30. The method according to any one of claims 26-28, wherein the vibrational stimulus has a frequency of 30 Hz to 90 Hz and an amplitude of 0.1 g to 1 g.

31. The method according to claim 29, wherein the vibrational stimulus is whole body vibration.

32. The method according to claim 30, wherein the vibrational stimulus is whole body vibration.

33. A method for mitigating muscle weakness in a subject, the method comprising:

a) providing a nutritional composition to a subject having or at risk of having muscle weakness, wherein the nutritional composition comprises at least one source of protein in an amount sufficient to provide 6 grams to 50 grams of protein per serving; and

whereby consumption of the nutritional composition and application of the vibrational stimulus is effective for mitigating muscle weakness in the subject.

34. The method according to claim 33, wherein the at least one source of protein is selected from the group consisting of whey protein concentrate, whey protein isolate, whey protein hydrolysate, acid casein, sodium caseinate, calcium caseinate, potassium caseinate, casein hydrolysate, milk protein concentrate, milk protein isolate, milk protein hydrolysate, nonfat dry milk, condensed skim milk, soy protein concentrate, soy protein isolate, soy protein hydrolysate, pea protein concentrate, pea protein isolate, pea protein hydrolysate, collagen protein, and combinations thereof.

35. The method according to claim 33, wherein the nutritional composition further comprises 0.4 grams to 4 grams of β-hydroxy β-methylbutyrate per serving.

36. The method according to any one of claims 33-35, wherein the vibrational stimulus has a frequency of 30 Hz to 50 Hz and an amplitude of 5 g to 20 g.

37. The method according to any one of claims 33-35, wherein the vibrational stimulus has a frequency of 30 Hz to 90 Hz and an amplitude of 0.1 g to 1 g.

38. The method according to claim 36, wherein the vibrational stimulus is whole body vibration.

39. The method according to claim 37, wherein the vibrational stimulus is whole body vibration.