Low lactose, low sugar, milk-based composition comprising GOS for use in improving muscle growth, function and / or mass

Abstract

Methods and compositions for promoting muscle growth, increasing muscle function and / or muscle mass in an adult subject in need thereof, the composition comprising a low sugar, low lactose, milk-based composition comprising galactooligosaccharide (GOS).

Description

TITLECOMPOSITIONS AND METHODS FOR IMPROVING MUSCLE HEALTHTECHNICAL FIELD

[0001] The present disclosure generally relates to compositions and methods for promoting muscle growth, increasing muscle function and / or muscle mass, for example to an adult subject in need thereof. Some embodiments are directed to a composition comprising milk protein and further comprising a mixture of lactose, glucose, galactose and galactooligosaccharide (GOS).BACKGROUND

[0002] Muscle is a vital tissue in the human body that plays a crucial role in movement, stability, and overall physical function. It is composed of muscle fibers that contract and relax to generate force and enable various activities.

[0003] Muscle health is essential for maintaining strength, mobility, and overall well-being. Imbalances in muscle metabolism or abnormalities in muscle function can lead to various disorders or conditions that affect muscle health.

[0004] Muscle disorders can range from muscle wasting conditions, such as muscular dystrophy, to metabolic disorders that impact muscle function, such as myopathies. Additionally, age-related muscle loss, known as sarcopenia, is a common concern that can lead to decreased muscle strength and functional limitations.

[0005] Maintaining muscle health is crucial for individuals of all ages, as it contributes to overall physical performance, quality of life, and independence. Healthy muscles provide support and stability to joints, enhance posture, and aid in the prevention of injuries.

[0006] Furthermore, muscle health is closely linked to metabolic health. Muscles are metabolically active tissues that play a significant role in energy expenditure and glucose metabolism. Maintaining healthy muscle mass and function can help regulate metabolism, improve insulin sensitivity, and reduce the risk of metabolic disorders such as type 2 diabetes.

[0007] Promoting muscle growth and preserving muscle mass requires a combination of regular physical activity, including resistance training, adequate protein intake, and overall balanced nutrition. Additionally, proper rest and recovery are essential for muscle repair and growth.

[0008] Although there exists to-day a large variety of active compounds, there is a constant need for new active compounds, in particular owing to the limited success of the current treatments, for providing composition for easy and convenient administration to any adult subject.SUMMARY

[0009] The present invention provides a method for promoting muscle growth, increasing muscle function and / or muscle mass in an adult subject.

[0010] In particular embodiments, the method for promoting muscle growth, increasing muscle function and / or muscle mass in an adult subject includes administering to an adult subject in need thereof a low sugar, low lactose, milk-based composition comprising galactooligosaccharide. In some embodiments, the composition comprises milk protein, preferably at 20-40 % by dry weight of the composition; and a mixture of lactose, glucose, galactose and galactooligosaccharide, the mixture preferably at 35-55% or 32-55%, by dry weight of the composition; preferably, the mixture comprising: 0.1 -30% by weight of the lactose, 8-40% by weight of the glucose, 0.1 -20% by weight of the galactose and 40-90% by weight of the galactooligosaccharide.

[0011] The promoting muscle growth, increasing muscle function and / or muscle mass in an adult subject comprises at least one result selected from the group consisting of: a) improving physical performance, endurance and / or strength; b) enhancing muscle metabolism; c) prevention and better recovery from injuries d) reducing muscle fatigue; e) increasing lean muscle mass; f) preventing frailty and / or sarcopenia; g) help maintaining functional independence and mobility with age and combinations thereof.

[0012] Additional features and advantages are described herein and will be apparent from the following Figures and Detailed Description.BRIEF DESCRIPTION OF THE DRAWINGS

[0013] FIG. 1 shows the increase in production of propionate metabolite after 24h fermentation of the active composition (MLG-H) by comparison to GOS alone or negative control (NSC) using batch fermentation.

[0014] FIG. 2 shows the increase in production of valerate metabolite after 24h fermentation of the active composition (MLG-H) by comparison to GOS alone or negative control (NSC) using batch fermentation.

[0015] FIG. 3 shows the increase in production of indole 3 carboxylate metabolite after 24h fermentation of the active composition (MLG-H) by comparison to GOS alone or negative control (NSC) using batch fermentation.

[0016] FIG. 4 shows the increase in production of N,N-Dimethylglycine metabolite after 24h fermentation of the active composition (MLG-H) by comparison to GOS alone or negative control (NSC) using batch fermentation.

[0017] FIG.5 shows the increase in production of tricarballylic acid metabolite after 24h fermentation of the active composition (MLG-H) by comparison to GOS alone or negative control (NSC) using batch fermentation.

[0018] FIG. 6 shows total SCFA production after 24h fermentation of the Active Composition (composition - LM) by comparison to regular milk (regular milk - LM) using batch fermentation with simulated lactose malabsorption.DETAILED DESCRIPTION

[0019] Definitions

[0020] Some definitions are provided hereafter. Nevertheless, definitions may be located in the “Embodiments” section below, and the above header “Definitions” does not mean that such disclosures in the “Embodiments” section are not definitions.

[0021] All percentages expressed herein are by weight of the total weight of the composition unless expressed otherwise. As used herein, “about,” “approximately” and “substantially” are understood to refer to numbers in a range of numerals, for example the range of -10% to +10% of the referenced number, preferably -5% to +5% of the referenced number, more preferably -1 % to +1 % of the referenced number, mostpreferably -0.1% to +0.1 % of the referenced number. All numerical ranges herein should be understood to include all integers, whole or fractions, within the range. Moreover, these numerical ranges should be construed as providing support for a claim directed to any number or subset of numbers in that range. For example, a disclosure of from 1 to 10 should be construed as supporting a range of from 1 to 8, from 3 to 7, from 1 to 9, from 3.6 to 4.6, from 3.5 to 9.9, and so forth.

[0022] As used in this disclosure and the appended claims, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a protein” or “the protein” includes two or more proteins.

[0023] The words “comprise,” “comprises” and “comprising” are to be interpreted inclusively rather than exclusively. Likewise, the terms “include,” “including” and “or” should all be construed to be inclusive, unless such a construction is clearly prohibited from the context. Nevertheless, the compositions and methods disclosed herein may lack any element that is not specifically disclosed herein. Thus, a disclosure of an embodiment using the term “comprising” includes a disclosure of embodiments “consisting essentially of” and “consisting of” the components or steps identified.

[0024] The terms “at least one of” and “and / or” used respectively in the context of “at least one of X and Y” and “X and / or Y” should be interpreted as “X without Y,” or “Y without X,” or “both X and Y.” Where used herein, the terms “example” and “such as,” particularly when followed by a listing of terms, are merely exemplary and illustrative and should not be deemed to be exclusive or comprehensive.

[0025] As used herein, “related to,” “associated with” and “linked with” mean occurring concurrently, preferably mean caused by the same underlying condition, more preferably mean that one of the identified conditions is at least indirectly caused by the other identified condition, and most preferably mean that one of the identified conditions is directly caused by the other identified condition.

[0026] The terms “food”, “food supplement”, “food product” and “food composition” mean a product or composition that is intended for ingestion by an individual such as a human and provides at least one nutrient to the individual. The compositions of the present disclosure, including the many embodiments describedherein, can comprise, consist of, or consist essentially of the elements disclosed herein, as well as any additional or optional ingredients, components, or elements described herein or otherwise useful in a diet supplement.

[0027] “Prevention” includes reduction of risk, incidence and / or severity of a condition or disorder. The terms “treatment” and “treat” include both prophylactic or preventive treatment (that prevent and / or slow the development of a targeted pathologic condition or disorder) and curative, therapeutic or disease-modifying treatment, including therapeutic measures that cure, slow down, lessen symptoms of, and / or halt progression of a diagnosed pathologic condition or disorder; and treatment of patients at risk of contracting a disease or suspected to have contracted a disease, as well as patients who are ill or have been diagnosed as suffering from a disease or medical condition. The terms “treatment” and “treat” do not necessarily imply that a subject is treated until total recovery. The terms “treatment” and “treat” also refer to the maintenance and / or promotion of health in an individual not suffering from a disease but who may be susceptible to the development of an unhealthy condition. The terms “treatment” and “treat” are also intended to include the potentiation or otherwise enhancement of one or more primary prophylactic or therapeutic measures. As nonlimiting examples, a treatment can be performed by a patient, a caregiver, a doctor, a nurse, or another healthcare professional.

[0028] As used herein, the term “lactose mal-absorber” refers to an adult subject who has a reduced ability to digest and absorb lactose, which is the sugar found in milk and dairy products. Lactose malabsorption occurs when the body does not produce enough lactase, the enzyme responsible for breaking down lactose into simpler sugars (glucose and galactose) that can be absorbed by the small intestine. Lactose malabsorption can be a result of various factors, including genetic predisposition, certain medical conditions (such as celiac disease or inflammatory bowel disease), or as a temporary condition following an illness or injury to the small intestine.

[0029] As used herein, the term “low lactose” shall refer to a composition with less than or equal to 30% of lactose.

[0030] As used herein, the term “low sugar” shall refer to a composition with less than or equal to 55% of the composition.

[0031] As used herein, a prophylactically or therapeutically “effective amount” is an amount that prevents a deficiency, treats a disease or medical condition in an individual, or, more generally, reduces symptoms, manages progression of the disease, or provides a nutritional, physiological, or medical benefit to the adult subject.

[0032] The term “composition” may mean a food, beverage, dietary supplement, complete nutrition or oral nutritional supplement (ONS) or medical food composition, or mixture thereof.

[0033] The composition can be in solid form (e.g., powder) or in liquid form. The amount of the various ingredients can be expressed in g / 100 g of the composition on a dry weight basis when it is in a solid form, e.g. a powder, or as a concentration in g / 100 mL of the composition when it refers to a liquid form (this latter also encompasses liquid composition that may be obtained from a powder after reconstitution in a liquid such as water.)

[0034] The term “unit dosage form,” as used herein, refers to physically discrete units suitable as unitary dosages for human and animal subjects, each unit containing a predetermined quantity of the composition disclosed herein in an amount sufficientto produce the desired effect, in association with an acceptable diluent, carrier or vehicle. The specifications for the unit dosage form depend on the particular compounds employed, the effect to be achieved, and the pharmacodynamics associated with each compound in the host.

[0035] The term “adult”, “adult subject” as used herein refers to young adults, adults, including pregnant or lactating women; perimenopausal or menopausal women, elderly.

[0036] “Galactooligosaccharides” (GOS) are oligosaccharides composed of different galactosyl residues (usually from 2 to 9 units) and a terminal glucose linked by P-glycosidic bonds, such as -(1-2), £-(1-3), £-(1-4), and £-(1-6). GOS are normally produced through the enzymatic conversion of lactose.

[0037] EmbodimentsIn an aspect of the present disclosure, a method of promoting muscle growth, increasing muscle function and / or muscle mass in an adult subject comprisesadministering to an adult subject in need thereof or at risk thereof a low sugar, low lactose, milk-based composition comprising galactooligosaccharide.

[0038] In some embodiments, the composition comprises 20-40 % by dry weight of milk protein; and 32-55% by dry weight of a mixture of lactose, glucose, galactose and galactooligosaccharide.

[0039] In some embodiments, the composition comprises 35-55% by dry weight of a mixture of lactose, glucose, galactose and galactooligosaccharide.

[0040] In an embodiment, the mixture of lactose, glucose and galactose and galactooligosaccharide comprises: 0.1 -30% by weight of lactose.

[0041] In an embodiment, the mixture of lactose, glucose and galactose and galactooligosaccharide comprises: 8-40% by weight of glucose.

[0042] In an embodiment, the mixture of lactose, glucose and galactose and galactooligosaccharide comprises: 0.1 -20% by weight of galactose.

[0043] In an embodiment, the mixture of lactose, glucose and galactose and galactooligosaccharide comprises 40-90% by weight of galactooligosaccharide.In an embodiment, the milk-based composition comprises: milk protein, preferably at 20-40 % by dry weight of the composition; and a mixture of lactose, glucose, galactose and galactooligosaccharide, the mixture preferably at 32-55% by dry weight of the composition; preferably, the mixture comprising: 0.1 -30% by weight of the lactose, 8-40% by weight of the glucose, 0.1 -20% by weight of the galactose and 40-90% by weight of the galactooligosaccharide.

[0044] In another embodiments, the milk-based composition comprises: milk protein, preferably at 20-40 % by dry weight of the composition; and a mixture of lactose, glucose, galactose and galactooligosaccharide, the mixture preferably at 35-55% by dry weight of the composition; preferably, the mixture comprising: 0.1 -30% by weight of the lactose, 8-40% by weight of the glucose, 0.1 -20% by weight of the galactose and 40-90% by weight of the galactooligosaccharide.

[0045] In some embodiments, the composition consists essentially of 20-40 % by dry weight of milk protein; and 32-55% by dry weight of a mixture of lactose, glucose, galactose and galactooligosaccharide.

[0046] In some embodiments, the composition consists essentially of 35-55% by dry weight of a mixture of lactose, glucose, galactose and galactooligosaccharide.In an embodiment, the milk-based composition consists essentially of: milk protein, preferably at 20-40 % by dry weight of the composition; and a mixture of lactose, glucose, galactose and galactooligosaccharide, the mixture preferably at 32-55% by dry weight of the composition; preferably, the mixture comprising: 0.1 -30% by weight of the lactose, 8-40% by weight of the glucose, 0.1 -20% by weight of the galactose and 40-90% by weight of the galactooligosaccharide.

[0047] In another embodiments, the milk-based composition consists essentially of : milk protein, preferably at 20-40 % by dry weight of the composition; and a mixture of lactose, glucose, galactose and galactooligosaccharide, the mixture preferably at 35-55% by dry weight of the composition; preferably, the mixture comprising: 0.1 -30% by weight of the lactose, 8-40% by weight of the glucose, 0.1 -20% by weight of the galactose and 40-90% by weight of the galactooligosaccharide.

[0048] Some embodiments provide a contribution from each of the components of the composition individually, in combination, and / or synergistically.

[0049] In particular embodiments, promoting muscle growth, increasing muscle function and / or muscle mass in an adult subject comprises at least one result selected from the group consisting of: a) improving physical performance, endurance and / or strength; b) enhancing muscle metabolism; c) prevention and better recovery from injuries d) reducing muscle fatigue; e) increasing lean muscle mass; f) preventing frailty and / or sarcopenia; g) help maintaining functional independence and mobility with age and combinations thereof.

[0050] Muscle function and mass

[0051] The compounds, compositions, uses and methods disclosed herein may provide for the maintenance of or increase in muscle function and / or mass.

[0052] The term “muscle function” refers to the ability of a muscle to perform in a manner that does not negatively impact on the life of a subject, and encompasses parameters of muscle strength, muscle contraction, muscle endurance, muscleelasticity, ability of a muscle to resist muscle fatigue and / or physical activities of daily living such as walking up stairs, getting out of a chair and other activities of daily living.

[0053] Suitable tests for assessing muscle function include grip strength assessment using a dynamometer; one repeat maximum on leg press, chest press or leg extension; gait speed; 6 min walk test; time up and go; short physical performance battery; Fried frailty criteria; and stair climbing time assessments. Other suitable tests include muscle strength, endurance and time to fatigue.

[0054] Muscle mass (which may equate with muscle volume, muscle thickness or myofiber size) may be measured by dual-energy X-ray absorptiometry (DXA) or bioimpedance tests. Similarly, MRI may be used for assessing muscle volume and ultra-sound may be used for assessing muscle thickness and pennation angle.

[0055] “Muscle wasting” may be a reduction in muscle mass, for example to the stage where the muscle loss becomes debilitating. In one embodiment, the subject does not lose more than 10%, 5%, 4%, 3%, 2% or 1% of their muscle mass.

[0056] The term “maintains” refers to a particular parameter, such as muscle function and / or mass, remaining substantially unchanged over a period of time (e.g. 5, 10, 15, 20, 25, 30, 40, 50 or more years).

[0057] In one embodiment, muscle mass increases by at least 1 %, 2%, 3%, 4%, 5%, 10%, 15% or 20%. In another embodiment, muscle mass increases by 1 -2.5%, 1 -5%, 1 -10% or 1 -20%.

[0058] Preferably, the muscle is skeletal muscle.

[0059] Muscle growth

[0060] In one embodiment of the present invention, as a result of maintenance of or increase in muscle function and / or mass, the compounds, compositions, uses and methods disclosed herein provide for promotion of muscle growth.

[0061] Within the context of the present invention the term “muscle growth” encompasses an increase of muscle mass, muscle volume and / or-muscle function, through time. Muscle growth may be evaluated by measuring muscle mass and / or function as above described.

[0062] Muscle growth can also be determined by an increase in muscle fiber number (hyperplasia) as well as an increase in muscle fiber size (hypertrophy).

[0063] Preferably, the muscle functionality that can be improved by the composition disclosed herein comprises a characteristic selected from the group consisting of muscle strength, gait speed, and combinations thereof. Muscle function is typically defined as strength per unit of appendicular skeletal muscle mass or per muscle volume.

[0064] The individual can be at risk of a disorder or condition (e.g., impairment in one or more of muscle functionality, muscle performance, or muscle strength), in which case the effective amount of the composition is a prophylactically effective dose; or the individual can have a disorder or condition, in which case the effective amount of the composition is a therapeutically effective dose. In some embodiments, the methods comprise identifying the individual as having the condition or being at risk of the condition before the administration.

[0065] The individual may be diagnosed with any of such condition(s) or may be suspected of having such condition(s) or may be susceptible to such condition(s). The adult subject may be treated with other therapy or therapies in addition to methods of the disclosure.

[0066] In other embodiment, the adult subject is healthy but may be experiencing unpleasant gastrointestinal manifestation following the consumption of specific food (e.g. lactose containing product, gluten containing product).

[0067] In another embodiment the adult subject is lactose mal-absorber.

[0068] In other embodiment, the adult subject may be of any age or state of health, although in particular embodiments the adult subject may be susceptible to particular medical conditions or physical states or genetic traits (e.g. lactase deficiency).

[0069] In specific embodiments, promoting muscle growth, increasing muscle function and / or muscle mass is associated with increased and / or decreased levels of certain metabolites, or functional derivatives thereof. In a preferred embodiment, promoting muscle growth, increasing muscle function and / or muscle mass is associated with increased levels of short chain fatty acids e.g. propionate, valerate, indole 3 carboxylate, N,N-dimethylglycine, 3-hydroxybutyrate, indole-3 propionate and / or tricarballylic acid.

[0070] Then, in an embodiment, the adult subject may be susceptible to particular medical conditions or physical states that would benefit from increasedmetabolite levels, or the adult subject may be suspected of having a medical condition or physical state that would benefit from increased metabolite levels, or increased beneficial fecal bacteria levels. The compositions delivered to the adult subject in such cases include a composition as described above, in particular to facilitate raising or lowering specific metabolite levels in the adult subject. One can measure specific metabolite levels through plasma or fecal samples, for example, in methods well known in the art.

[0071] The method may comprise identifying the adult subject as having a medical condition or physical state or genetic condition that would benefit from increased metabolite levels, or increased beneficial fecal bacteria levels, and / or the method may comprise identifying the adult subject as at risk of a medical condition or physical state that would benefit from increased metabolite levels.

[0072] In specific embodiments, an adult subject is provided effective amounts of compositions as described herein for the explicit purpose of raising intracellular levels of short chain fatty acids e.g. propionate, valerate, indole 3 carboxylate, N,N-dimethylglycine, 3-hydroxybutyrate, indole-3 propionate and / or tricarballylic acid, because it is determined that the adult subject is afflicted with a condition for which such levels are directly or indirectly related.

[0073] Composition for use

[0074] In some embodiments, the composition comprises 20-40% by dry weight of milk protein. Milk protein includes any protein or combination of proteins derived from milk. The milk proteins may have been derived from milkin any suitable way. In a preferred embodiment, the composition comprises 25-40%, more preferably 30- 40% by dry weight of milk protein.

[0075] In some embodiments, the food ingredient further comprises 35-55%, more preferably 32-55%, by dry weight of a mixture of lactose, glucose, galactose and GOS, the mixture comprising: 0.1 -30% by weight of lactose, 8-40% by weight of glucose, 0.1 -20% by weight of galactose and 40-90% by weight of GOS. In a preferred embodiment, the food ingredient comprises 45-55% by dry weight of the mixture of lactose, glucose, galactose and GOS; in a more preferred embodiment, the food ingredient comprises 50-55% by dry weight of the mixture of lactose, glucose, galactoseand GOS. In another preferred embodiment of the invention, the mixture of lactose, glucose, galactose and GOS comprises 60-90% by weight of GOS, more preferred 70- 90% by weight of GOS. In yet another preferred embodiment, the mixture of lactose, glucose, galactose and GOS contains: 1 -20% by weight of lactose, 15-35% by weight of glucose, 1 -10% by weight of galactose and 50-85% by weight of GOS. In a more preferred embodiment of the invention, the mixture of lactose, glucose, galactose and GOS contains: 1 -14% by weight of lactose, 15-29% by weight of glucose, 1 -8% by weight of galactose and 70-90% by weight of GOS.

[0076] In some embodiments, the mixture of lactose, glucose, galactose and GOS comprises 0.1 -30%, such as 0.1 -5%, 5-10%, 10-15%, 15-20%, 20-25%, or 25-30% by weight of lactose. In some embodiments, the mixture of lactose, glucose, galactose and GOS comprises 8-40%, such as 8-16%, 16-24%, 24-32%, or 32-40%, by weight of glucose. In some embodiments, the mixture of lactose, glucose, galactose and GOS comprises 0.1 -20%, such as 0.1 -5%, 5-10%, 10-15%, or 15-20%, by weight of galactose. In some embodiments, the mixture of lactose, glucose, galactose and GOS comprises 40-90%, such as 40-50%, 50-60%, 60-70%, or 70-80% by weight of GOS.

[0077] The composition may further comprise 0.5-30% by dry weight of milkfat and / or minerals derived from milk, preferably 2-20%, more preferably 6-10% by dry weight of milk fat and / or minerals derived from milk. Milk fat includes fat derived from milk in any suitable way. Milk derived minerals include minerals derived from milk in any suitable way, e.g. calcium, sodium, potassium, phosphorus and / or magnesium salts. Milk fat and / or milk derived minerals may originate from liquid milk, such as skim milk, partially skimmed milk and / or whole milk, or from milk powder, such as e.g. skim milk powder and / or whole milk powder.

[0078] The composition may further comprise 0.5-30% by dry weight of at least one of milk fat or mineral derived from milk, preferably a combination thereof. The composition may further comprise 5-20% by dry weight of vegetable oil.

[0079] In a preferred embodiment, the composition further comprises 5-20% by dry weight of vegetable oil, more preferably 8-15% by dry weight of vegetable oil. The vegetable oil may be any suitable vegetable oil, preferably palm oil. In one embodiment, the composition relates to a cocoa, coffee, fruit based and / or malt beverage powder comprising: 10-35% by weight of non-fat milk solids; 0-65% by weight of malt extractsolids; 0-15% by weight of cocoa solids; 6-15% by weight of vegetable oil and / or milk fat; 0-25% by weight of sucrose; 1 -6% by weight of glucose; 0.1 -5% by weight of lactose; and 3-10% by weight of GOS.

[0080] In a preferred embodiment, the invention relates to a cocoa and malt beverage powder comprising 15-35% by weight of non-fat milk solids; 20-50% by weight of malt extract solids; 5-15% by weight of cocoa solids; 6-15% by weight of vegetable oil and / or milkfat; 0-25% by weight of sucrose; 1 -6% by weight of glucose; 0.1 -5% by weight of lactose; and 3-10% by weight of galactooligosaccharide.

[0081] In one embodiment, the composition relates to a liquid cocoa and / or malt beverage product comprising: 3-10% by weight of non-fat milk solids; 1 -6% by weight of malt extract solids; 0-5% by weight of cocoa solids; 0.3-5% by weight of vegetable oil and / or milk fat; 0-5% by weight of sucrose; 0.4-1 .5% by weight of glucose; 0.01 -1 % by weight of lactose; and 0.5-5% by weight of GOS.

[0082] A liquid cocoa and / or malt beverage product is a cocoa and / or malt beverage product in liquid form which is suitable to be consumed without addition of liquid. It may e.g. be packed in a container from which it can be consumed directly upon opening.

[0083] Non-fat milk solids may be derived from any suitable milk source, such as e.g. liquid milk, e.g. skim milk and / or whole milk, and / or milk powder, e.g. skim milk powder and / or whole milk powder. If liquid milk is used, it may be concentrated, e.g. by evaporation or filtration. Malt extract solids may be in any suitable form, e.g. in the form of a powdered or liquid extract of malted barley and / or wheat. Cocoa solids may be from any suitable cocoa source, e.g. in the form of cocoa powder, cocoa mass and / or cocoa butter. Vegetable oil may be any suitable vegetable oil, preferably palm oil. Milk fat may be derived from any suitable milk source, such as e.g. liquid milk or cream, e.g. skim milk, cream, and / or whole milk, and / or milk powder, e.g. skim milk powder, cream powder, and / or whole milk powder, and / or may be in the form of butter, butter oil and / or anhydrous milk fat. If liquid milk or cream is used, it may be concentrated, e.g. by evaporation or filtration.

[0084] Glucose, lactose and GOS are preferably derived from the composition of the present invention. A liquid cocoa and / or malt beverage product of the invention preferably comprises 10-30% by dry weight of the composition of the invention, morepreferably 15-25% by dry weight. In a preferred embodiment, the liquid cocoa and / or malt beverage product comprises 0.5-1 % by weight of glucose; 0.01 -0.5% by weight of lactose; and 1 -4% by weight of GOS.

[0085] A liquid cocoa and / or malt beverage product of the invention may comprise sucrose. Due to the amounts of lactose, glucose and GOS present in the product, the amount of sucrose may be reduced as compared to a conventional cocoa and / or malt beverage powder while retaining an acceptable taste, sweetness and texture. In a preferred embodiment, a cocoa and / or malt beverage product of the invention does not comprise sucrose. In another preferred embodiment, a cocoa and / or malt beverage powder of the invention comprises 0.1 -5% by weight of sucrose, more preferably 1 -3% by weight of sucrose.

[0086] A liquid cocoa and / or malt beverage product of the invention may comprise any other suitable ingredients known in the art, such as e.g. vitamins, minerals, buffer salts, emulsifiers and stabilizers.

[0087] A liquid cocoa and / or malt beverage product of the invention may be produced in any suitable way known in the art. The ingredients may be in liquid and / or powdered form and may be mixed into an aqueous solution / suspension, e.g. with the addition of water to achieve the desired concentration of ingredients. A food ingredient of the invention is preferably added in liquid form, but may also be added in powdered form.

[0088] In a preferred embodiment, the composition relates to a liquid cocoa and / or malt beverage product comprising: 3-10% by weight of non-fat milk solids; 1 -6% by weight of malt extract solids; 1 -5% by weight of cocoa solids; 0.3-5% by weight of vegetable oil and / or milk fat; 0-5% by weight of sucrose; 0.4-1 .5% by weight of glucose; 0.01 -1 % by weight of lactose; and 0.5-5% by weight of GOS.

[0089] The composition can be in any oral nutritional form, e.g., as a health drink, as a ready-made drink, optionally as a soft drink, including juices, coffee, tea, milkshake, yogurt drink, smoothie or soy-based drink; in a food bar; a powder, such as in sachet form; or dispersed in foods of any sort, such as baked products, cereal bars, dairy bars, snack-foods, soups, breakfast cereals, muesli, candies, tabs, cookies, biscuits, crackers (such as rice crackers), and dairy and plant-based products.

[0090] In some embodiments, the composition relates to a ready to drink beverage. The % weight are based on dry matter of the composition before reconstitution. In an embodiment, the ready to drink beverage comprises 32%-55% of a mixture of Lactose, Glucose, Galactose, and GOS. In an embodiment, the composition comprises 40-45% by dry weight of the mixture of lactose, glucose, galactose and GOS. In an embodiment, the composition comprises 45-50% by dry weight of the mixture of lactose, glucose, galactose and GOS. In an embodiment, the food ingredient comprises 32-37% by dry weight of the mixture of lactose, glucose, galactose and GOS.

[0091] In some embodiments, the mixture of Lactose, Glucose, Galactose and GOS in the composition contains 1 -25% by weight of lactose, such as 1 -5%, 5-10%, 10- 15%, 15-20%, or 20-25% by weight of lactose. In some embodiments, the mixture of Lactose, Glucose, Galactose and GOS in the composition contains 15-35% by weight of glucose, such as 15-20%, 20-25%, 25-30%, or 30-35% by weight of glucose. In some embodiments, the mixture of Lactose, Glucose, Galactose and GOS in the composition contains 1 -10% by weight of galactose, such as 1 -2%, 2-4%, 4-6%, 6-8%, or 8-10% by weight of galactose. In some embodiments, the mixture of Lactose, Glucose, Galactose and GOS in the composition contains 50-85% by weight of GOS, such as 50-60%, 60- 70%, 70-80%, or 80-85% by weight of GOS.

[0092] In a preferred embodiment, the composition comprises 40-45% of a mixture of Lactose, Glucose, Galactose and GOS. In a preferred embodiment, the mixture of Lactose, Glucose, Galactose and GOS in the composition contains 10-20% by weight of lactose. In a preferred embodiment, the mixture of Lactose, Glucose, Galactose and GOS in the composition contains 15-25% by weight of glucose. In a preferred embodiment, the mixture of Lactose, Glucose, Galactose and GOS in the composition contains 0.1 -5% by weight of galactose. In a preferred embodiment, the mixture of Lactose, Glucose, Galactose and GOS in the composition contains 57-70% by weight of GOS.

[0093] In some embodiments, the ready to drink beverage includes milk. In some embodiments, the milk includes full milk, skim milk, and other types of milk. In some embodiments, the ready to drink beverage is optionally fortified with one or more vitamins and minerals.

[0094] In some embodiments, the composition does not contain vitamins and / or mineral fortification, in particular calcium fortification.

[0095] In one preferred embodiment, the composition is a maternal supplement. The supplement is preferably taken throughout pregnancy to build up maternal stores of the various constituent components, although supplementation in the second and more particularly the third trimesters is believed to be particularly advantageous. Likewise, supplementation may continue after birth either via continued consumption of the composition by the mother if the baby is to be breast fed, or by administering a similar composition directly to the baby, for example byway of an infant formula used to feed the baby.

[0096] The composition can be administered to the adult subject at least two days perweek, at least three days perweek, all seven days of the week respecting serving size; for at least one week, at least one month, at least two months, at least three months, at least six months, or even longer. In some embodiments, the composition is administered to the adult subject consecutively for a number of days. In an embodiment, the composition can be administered to the adult subject daily for at least 30, 60 or 90 consecutive days.

[0097] In some embodiments, the serving size of the composition is an amount effective to increase certain metabolites or certain bacteria such as Bifidobacteria, for example, about 100 ml, about 200 ml, about 300 ml, about 400 ml or about 500ml of the composition. In some embodiments, the composition is administered in a unit dosage form that comprises an amount of the composition effective for increasing or decreasing certain metabolites and improving health.

[0098] In view of the disclosures herein, an embodiment is method for promoting muscle growth, increasing muscle function and / or muscle mass, the method comprising administering to an adult subject in need thereof a low sugar, low lactose, milk-based composition comprising galactooligosaccharide. In some embodiments, the composition is as described above.

[0099] The promoting muscle growth, increasing muscle function and / or muscle mass in an adult subject comprises at least one result selected from the group consisting of: muscle growth, increasing muscle function and / or muscle mass in an adult subject comprises at least one result selected from the group consisting of: a)improving physical performance, endurance and / or strength; b) enhancing muscle metabolism; c) prevention and better recovery from injuries d) reducing muscle fatigue; e) increasing lean muscle mass; f) preventing frailty and / or sarcopenia; g) help maintaining functional independence and mobility with age and combinations thereof.

[0100] Another aspect of the present disclosure is a method for promoting muscle growth, increasing muscle function and / or muscle mass, the method comprising administering to an adult subject in need thereof or at risk thereof any of the compositions disclosed herein. The composition may be administered in an amount effective for increasing levels of short chain fatty acids e.g. propionate, valerate, indole 3 carboxylate, N,N-dimethylglycine, 3-hydroxybutyrate, indole-3 propionate and / or tricarballylic acid. The Research has shown that increasing propionate orvalerate levels have been linked to the listed benefits (See Han, Joo-Hui et al. “The effects of propionate and valerate on insulin responsiveness for glucose uptake in 3T3-L1 adipocytes and C2C12 myotubes via G protein-coupled receptor 41 .” PloS one vol. 9,4 e95268. 18 Apr. 2014; Scheiman, J., et al. (2019). "Meta-omics analysis of elite athletes identifies a performance-enhancing microbe that functions via lactate metabolism." Nat Med 25(7): 1104-1109; Frampton, J., et al. (2020). "Short-chain fatty acids as potential regulators of skeletal muscle metabolism and function." Nat Metab 2(9): 840-848; Zhao-Bo Luo, Shengzhong Han, Xi-Jun Yin, Hongye Liu, Junxia Wang, Meifu Xuan, Chunyun Hao, Danqi Wang, Yize Liu, Shuangyan Chang, Dongxu Li, Kai Gao, Huiling Li, Biaohu Quan, Lin-Hu Quan, Jin-Dan Kang (2023) Fecal transplant from myostatin deletion pigs positively impacts the gut-muscle axis eLife 12:e81858.) Moreover, Valerate levels have been linked to the listed benefits (see Zhao-Bo Luo et al. Fecal transplant from myostatin deletion pigs positively impacts the gut-muscle axis, Development Biology, 2023 https: / / doi.Org / 10.7554 / eLife.81858). Indole 3-carboxylate levels have been linked to the listed benefits (see Park I., et al. Gut Microbiota-Derived lndole-3-Carboxylate Influences Mucosal Integrity and Immunity Through the Activation of the Aryl Hydrocarbon Receptors and Nutrient Transporters in Broiler Chickens Challenged With Eimeria maxima. Front. Immunol. 2022 Jun 23; 13:867754). N,N-Dimethylglycine levels have been linked to the listed benefits (see Li Y. et al. Effects of slaughter weight on carcass characteristics, meat quality, and metabolomics profiling in the longissimus dorsi muscle of Tianfu finishing pigs. Front. Vet. Sci., 28 June 2024 Sec. Animal Nutritionand Metabolism, Volume 11 - 2024). Tricarballylic acid levels have been linked to the listed benefits (see. Greene E., et al. Muscle Metabolome Profiles in Woody Breast- (un)Affected Broilers: Effects of Quantum Blue Phytase-Enriched Diet. Front. Vet. Sci., 4 August 2020 Sec. Animal Nutrition and Metabolism, Volume 7 - 2020). 3-hydroxybutirate levels have been linked to the listed benefits (see Thomsen, Henrik H et al. “Effects of 3- hydroxybutyrate and free fatty acids on muscle protein kinetics and signaling during LPS- induced inflammation in humans: anticatabolic impact of ketone bodies.” The American journal of clinical nutrition vol. 108,4 (2018): 857-867). Indole-3 propionic acid levels have been linked to the listed benefits (see Du, L.; Qi, R.; Wang, J.; Liu, Z.; Wu, Z. Indole- 3-Propionic Acid, a Functional Metabolite of Clostridium sporogenes, Promotes Muscle Tissue Development and Reduces Muscle Cell Inflammation. Int. J. Mol. Sci. 2021 , 22, 12435).

[0101] The composition may be administered to the adult subject in a unit dosage form, wherein the unit dosage form.

[0102] In an embodiment, the composition according to the present invention has been shown to increase production of SCFA by comparison to regular milk in lactose malabsorbers. Moreover, the processus of fermentation was shown to be optimized, with the composition leading to more SCFA production for less gas being produced than regular milk. This phenomenon could improve gut comfort, by minimizing colonic gaz production (responsible for bloating, flatulence and discomfort) while retaining the benefit associated with bacterial fermentation in the colon (SCFA production). In a particular embodiment, the composition according to the present invention, produces less gas for the same amount of SCFA produced as exemplified below. Additionally, our composition was shown to produce similar amount of gas in lactose malabsorption condition than in regular condition, suggesting that it should not induced gas-associated discomfort in lactose malabsorbers.EXAMPLES

[0103] The following non-limiting example generally illustrates the concepts underlyingthe embodiments disclosed herein.

[0104] Example 1

[0105] In-vitro batch fermentation experiment was set up to compare the effect of 24h fermentation of GOS or the active composition on the microbial metabolism in healthy adults (H) or in adults with lactose malabsorption (LM). For this, the active composition accordingtoTable 1 was subjected to a simulation of uppergastrointestinal tract digestion according to the INFOGEST 2.0 method (Brodkorb et al) to mimic the human upper gastro-intestinal tract digestion before being introduced in the fermenters. This step removed small sugars such as lactose, glucose and galactose. The in vitro digestion process also removed some of the GOS (which is contrary to what is observed in vivo in human where GOS remains undigested in the upper gastrointestinal tract). For these reasons, some GOS was directly added in the fermenters to mimic human digestion; final concentrations of GOS are presented in Table 2. In other experiments, lactose (+ / - GOS) was added to the fermenters to mimic human lactose malabsorption (LM); final concentrations of lactose are presented in Table 2. A negative control was also introduced to evaluate the basal microbial metabolism after 24h without any substrate addition (NSC). Each condition was tested using fecal inoculum of 12 healthy adult donors. Microbial metabolites (including short chain fatty acids) were measured using a combination of targeted and untargeted metabolomics approaches by ultra-high performance liquid chromatography mass spectrometry (UPLC-MS). Significant differences in microbial metabolite production between conditions were calculated using paired-t test (*<pvalue=0.05; **<p-value=0.01 ; ***<p-value=0.001 ).

[0106] Table 1 : Active composition

[0107] Table 2: Final concentrations of Lactose and GOS before in-vitro batch fermentation.

[0108] Results

[0109] FIGS. 1 to 5 include box plots showing significant increase in production of propionate, valerate, indole 3 carboxylate, N,N-dimethylglycine and tricarballylic acid metabolite, after 24h fermentation of the composition disclosed herein by comparison to GOS alone or negative control (NSC) using batch fermentation.

[0110] The box plots displayed the median, the 25thand 75thpercentile and the distribution of the metabolite level for each donor (n=12) after 24h fermentation in mM for propionate and valerate or in arbitrary unit (A.U) for NN-dimethylglycine, tricarballylic acid or indole 3-carboxylate. A significant increase in these metabolites was found after 24h fermentation of the active composition by comparison to GOS alone or in the NSC highlighting a boost in the production of microbial metabolites with known muscle- related benefits. Indeed, Research has shown that increasing propionate or valerate levels have been linked to the listed benefits (See Han, Joo-Hui et al. “The effects of propionate and valerate on insulin responsiveness for glucose uptake in 3T3-L1 adipocytes and C2C12 myotubes via G protein-coupled receptor 41 .” PloS one vol. 9,4 e95268. 18 Apr. 2014; Scheiman, J., et al. (2019). "Meta-omics analysis of elite athletes identifies a performance-enhancing microbe that functions via lactate metabolism." Nat Med 25(7): 1104-1109; Frampton, J., et al. (2020). "Short-chain fatty acids as potential regulators of skeletal muscle metabolism and function." Nat Metab 2(9): 840-848; Zhao- Bo Luo, Shengzhong Han, Xi-Jun Yin, Hongye Liu, Junxia Wang, Meifu Xuan, Chunyun Hao, Danqi Wang, Yize Liu, Shuangyan Chang, Dongxu Li, Kai Gao, Huiling Li, Biaohu Quan, Lin-Hu Quan, Jin-Dan Kang (2023) Fecal transplant from myostatin deletion pigspositively impacts the gut-muscle axis eLife 12:e81858). Moreover, Valerate levels have been linked to the listed benefits (see Zhao-Bo Luo et al. Fecal transplant from myostatin deletion pigs positively impacts the gut-muscle axis, Development Biology, 2023 https: / / doi.org / 10.7554 / eLife.81858). Indole 3-carboxylate levels have been linked to the listed benefits (see Park I., et al. Gut Microbiota-Derived lndole-3-Carboxylate Influences Mucosal Integrity and Immunity Through the Activation of the Aryl Hydrocarbon Receptors and Nutrient Transporters in Broiler Chickens Challenged With Eimeria maxima. Front. Immunol. 2022 Jun 23; 13:867754). N,N-Dimethylglycine levels have been linked to the listed benefits (see Li Y. et al. Effects of slaughter weight on carcass characteristics, meat quality, and metabolomics profiling in the longissimus dorsi muscle of Tianfu finishing pigs. Front. Vet. Sci., 28 June 2024 Sec. Animal Nutrition and Metabolism, Volume 11 - 2024). Tricarballylic acid levels have been linked to the listed benefits (see. Greene E., et al. Muscle Metabolome Profiles in Woody Breast- (un)Affected Broilers: Effects of Quantum Blue Phytase-Enriched Diet. Front. Vet. Sci., 4 August 2020 Sec. Animal Nutrition and Metabolism, Volume 7 - 2020).

[0111] FIG. 6 shows the slight increase in SCFA production (+8%) after 24h fermentation of the composition disclosed herein by comparison to regular milk using batch fermentation with simulated lactose malabsorption (LM). This indicates that despite producing less gas, the Active Composition leads to more production of SCFA with the associated health benefit as described herein. The processus of fermentation is optimized with the Active Composition leading to more SCFA production for less gas being produced, potentially improving gut comfort while retaining the benefit associated with bacterial fermentation in the colon.

Claims

CLAIMSClaim 1 : A method for promoting muscle growth, increasing muscle function and / or muscle mass, the method comprising administering to an adult subject in need thereof a low sugar, low lactose, milk-based composition comprising galactooligosaccharide.Claim 2: The method of claim 1 , wherein the composition comprises 35-55% by dry weight of a mixture of lactose, glucose, galactose and galactooligosaccharide.Claim 3: The method of claim 1 or 2, wherein the composition comprises 20-40 % by dry weight of milk protein; and 32-55% by dry weight of a mixture of lactose, glucose, galactose and galactooligosaccharide.Claim 4: The method of any of claims 2 to 3, wherein the mixture of lactose, glucose and galactose and galactooligosaccharide comprises 0.1 -30% by weight of lactose.Claim 5: The method of any of claims 2 to 4, wherein the mixture of lactose, glucose and galactose and galactooligosaccharide comprises: 8-40% by weight of glucose.Claim 6: The method of any of claims 2 to 5, wherein the mixture of lactose, glucose and galactose and galactooligosaccharide comprises: 0.1 -20% by weight of galactose.Claim 7: The method of any of claims 2 to 6, wherein the mixture of lactose, glucose and galactose and galactooligosaccharide comprises 40-90% by weight of galactooligosaccharide.Claim 8: The method of any of preceding claims, wherein the milk-based composition comprises: milk protein, preferably at 20-40 % by dry weight of the composition; and a mixture of lactose, glucose, galactose and galactooligosaccharide, the mixture preferably at 32-55% by dry weight of the composition; preferably, the mixture comprising: 0.1 -30% by weight of the lactose, 8-40% by weight of the glucose, 0.1 -20% by weight of the galactose and 40-90% by weight of the galactooligosaccharide.Claim 9: The method of any preceding claims, wherein the promoting muscle growth, increasing muscle function and / or muscle mass in an adult subject comprises at least one result selected from the group consisting of: a) improving physical performance, endurance and / or strength; b) enhancing muscle metabolism; c) prevention and better recovery from injuries d) reducing muscle fatigue; e) increasing lean muscle mass; f) preventing frailty and / or sarcopenia; g) help maintaining functional independence and mobility with age and combinations thereof.Claim 10: The method of claim 9, wherein the composition is administered in an amount effective for increasing levels of short chain fatty acids e.g. propionate, valerate, indole 3 carboxylate, N,N-dimethylglycine, 3-hydroxybutyrate, indole-3 propionate and / or tricarballylic acid.Claim 11 : The method of any preceding claim, wherein the composition is administered to the adult subject in a unit dosage form.Claim 12: The method according to any preceding claim, wherein the adult subject isyoung adult, adult, including pregnant or lactating women; perimenopausal or menopausal women, elderly.Claim 13: The method according to any preceding claim, wherein the adult subject is lactose mal-absorber.

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