EP4284355A1 - Methods and nutritional compositions for improving muscle energy production and/or strength - Google Patents
Methods and nutritional compositions for improving muscle energy production and/or strengthInfo
- Publication number
- EP4284355A1 EP4284355A1 EP22704098.7A EP22704098A EP4284355A1 EP 4284355 A1 EP4284355 A1 EP 4284355A1 EP 22704098 A EP22704098 A EP 22704098A EP 4284355 A1 EP4284355 A1 EP 4284355A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- protein
- hmb
- nutritional composition
- oil
- day
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
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- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000011885 synergistic combination Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 235000019157 thiamine Nutrition 0.000 description 1
- 229960003495 thiamine Drugs 0.000 description 1
- 239000011721 thiamine Substances 0.000 description 1
- KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 235000019163 vitamin B12 Nutrition 0.000 description 1
- 239000011715 vitamin B12 Substances 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 235000019168 vitamin K Nutrition 0.000 description 1
- 239000011712 vitamin K Substances 0.000 description 1
- 150000003721 vitamin K derivatives Chemical class 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 229940011671 vitamin b6 Drugs 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 229940046010 vitamin k Drugs 0.000 description 1
- 230000001755 vocal effect Effects 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
Definitions
- the present invention relates to methods for improving muscle energy production and/or muscle strength in a subject, and/or for reducing muscle loss in a subject, and to nutritional compositions suitable for use, inter alia, to improve muscle energy production and/or muscle strength, and/or for reducing muscle loss.
- Sarcopenia is defined as any loss of skeletal muscle mass and strength secondary to aging and/or chronic disease associated with a hypercatabolism state.
- Sarcopenia includes both muscle loss and muscle dysfunction, which involves contractile impairment and metabolic and endocrine abnormalities.
- Sarcopenia affects more than 25% of men over 60 years of age and close to 20% of women over 60 years of age, and over half of both men and women over the age of 80.
- mitochondrial dysfunction and aberrant bioenergetics are key players in the development of the pathology.
- Skeletal muscle fiber contraction permits locomotion and other body movements, maintenance of posture, respiration (diaphragm and intercostal muscles) and communication (verbal and facial muscles).
- Contraction of a muscle which acts as a secretory organ, stimulates production, secretion, and expression of cytokines or myokines (other muscle fiber- derived peptides).
- Contraction-induced myokines influence crosstalk between different organs in an autocrine, endocrine, or paracrine fashion and have positive effects on glucose uptake, glucose tolerance, regulation of fat oxidation, and satellite cell proliferation. Accordingly, contractile impairment in muscle has a variety of adverse effects on an individual. Decreased contractility leads to loss of strength (i.e. , dynapenia), fatigue, disability and falls, impaired pulmonary ventilation, osteoporosis, and fractures due to reduced mechanical bone stimulation in patients with chronic disease and the elderly.
- ATP adenosine triphosphate
- ADP adenosine diphosphate
- muscle cells can operate at a basal level that only requires a part of their total ATP-producing capacity, there are certain circumstances in which muscle cells require a sudden burst of energy. For example, muscle cells may need to respond to stress or increased workload, in which case more ATP will be required to maintain cellular functions.
- SRC spare respiratory capacity
- SRC is one of the most important aspects of mitochondrial bioenergetics. It is well known that the energy requirements of different tissues fluctuate and that ATP synthesis is correspondingly up- or downregulated to accurately meet tissue energy demands. A cell with a larger SRC can produce more ATP to overcome more stress. This becomes particularly important in electrically excitable cells such as muscle cells, which face periods of high ATP demand to re-establish ion gradients necessary to drive muscular contraction. Mitochondrial SRC is regarded as a crucial aspect of mitochondrial function. When energy demand exceeds supply (e.g. an increase in workload), the SRC has the potential to increase supply, thus, avoiding an “ATP crisis”.
- energy demand exceeds supply (e.g. an increase in workload)
- the SRC has the potential to increase supply, thus, avoiding an “ATP crisis”.
- the invention is directed to methods for improving muscle energy production and/or muscle strength in a subject, and/or for reducing muscle loss in a subject.
- the methods comprise administering beta-hydroxy beta-methylbutyrate (HMB) and at least one citrus flavonoid to the subject.
- HMB beta-hydroxy beta-methylbutyrate
- the invention is directed to nutritional compositions comprising protein, fat, carbohydrate, HMB, and at least one citrus flavonoid.
- FIG. 1 shows the effects of HMB and flavonoid-containing citrus extract, individually, and a combination thereof on the oxygen consumption rate (OCR) in C2C12 myotubes treated with dexamethasone (DEX), as described in the Example;
- Fig. 2 shows the effects of HMB and hesperidin, individually, and a combination thereof on the oxygen consumption rate (OCR) in C2C12 myotubes treated with dexamethasone (DEX), as described in the Example; and
- Fig. 3 shows the effects of HMB and hesperetin, individually, and a combination thereof on the oxygen consumption rate (OCR) in C2C12 myotubes treated with dexamethasone (DEX), as described in the Example.
- OCR oxygen consumption rate
- compositions described herein may comprise, consist of, or consist essentially of the essential steps and elements, respectively, as described herein, as well as any additional or optional steps and elements, respectively, described herein. Any combination of method or process steps as used herein may be performed in any order, unless otherwise specified or clearly implied to the contrary by the context in which the referenced combination is made.
- the various embodiments of the nutritional compositions of the invention may also be substantially free of any optional or selected ingredient or feature described herein, provided that the remaining nutritional composition still contains all of the required ingredients or features as described herein.
- the term “substantially free” means that the selected nutritional composition contains less than a functional amount of the optional ingredient, typically less than 1%, including less than 0.5%, including less than 0.1%, and also including zero percent, by weight, of such optional or selected essential ingredient.
- the invention is directed to methods for improving muscle energy production and/or muscle strength in a subject, and/or reducing muscle loss in a subject.
- the present methods improve mitochondrial function by increasing the efficiency of energy production to match energy demand, resulting in improved muscle contraction and counteracting mitochondrial dysfunction associated with, for example, aging and hypercatabolic states. Improved muscle energy production and/or muscle strength and/or reduced muscle loss result.
- the methods conveniently provide such improvements by administering beta-hydroxy beta-methylbutyrate (HMB) and at least one citrus flavonoid to the subject.
- HMB beta-hydroxy beta-methylbutyrate
- the invention is directed to nutritional compositions comprising HMB and at least one citrus flavonoid.
- the inventive nutritional compositions provide a convenient means for conducting the inventive methods.
- the subject is in need of improved muscle energy production or muscle strength.
- the subject may have or be at risk of reduced muscle contractile function and/or at risk of muscle loss.
- reduced muscle contractile function can be evidenced by loss of strength, fatigue, disability and falls, impaired pulmonary ventilation, osteoporosis, and fractures due to reduced mechanical bone stimulation.
- Reduced muscle contractile function is often associated with sarcopenia, hospitalization, and/or an acute or chronic disease with a hypercatabolic state.
- the subject may be experiencing or at risk of one or more of sarcopenia, hospitalization, and/or an acute or chronic disease with a hypercatabolic state.
- the subject may be of at least 40 years of age, of at least 50 years of age, of at least 60 years of age, of at least 70 years of age, or of at least 80 years of age. Such subjects may be suffering from or at risk of experiencing reduced muscle contractile function or at risk of muscle loss.
- the subject is a human subject.
- Any suitable source of HMB may be employed in the methods and nutritional compositions of the invention, including the free acid, a salt, including hydrated or anhydrous salts, an ester, a lactone, or other product form that otherwise provides a bioavailable form of HMB when administered.
- Non-limiting examples of suitable salts of HMB for use herein include HMB salts, hydrated or anhydrous, of sodium, potassium, magnesium, chromium, calcium, or other non-toxic salt form.
- the HMB is in the form of calcium HMB, or, more specifically, calcium HMB monohydrate.
- HMB is administered to the subject in an amount of about 0.1 to about 10 g/day, about 0.1 to about 5 g/day, about 0.5 to about 5 g/day, about 0.5 to about 3 g/day, or about 0.5 to about 1.5 g/day.
- citrus flavonoids are suitable for use in the present methods and nutritional compositions.
- examples include, but are not limited to, hesperidin, hesperetin, which is the aglycone of hesperidin, narirutin, diosmin, isonaringin, naringin, and didymin, which may be used alone or in combinations of any two or more.
- the citrus flavonoid comprises hesperidin, hesperetin, or a combination thereof.
- Hesperidin is the major flavonoid present in sweet oranges, but is also found in other citrus fruits including lemon, lime, grapefruit, mandarin, and other classes of orange.
- citrus flavonoid is administered in an amount of about 50 to about
- the HMB and at least one citrus flavonoid may be administered simultaneously or sequentially.
- the HMB and at least one citrus flavonoid are administered to the subject simultaneously in a nutritional composition.
- the HMB and at least one citrus flavonoid are administered to the subject simultaneously in a nutritional composition comprising protein, fat and carbohydrate.
- HMB and at least one citrus flavonoid are administered to the subject daily for a period of time.
- the HMB and at least one citrus flavonoid are administered to the subject one, two or three or more times per day, for a period of 5 days, 7 days, 10 days, two weeks, one month, or more.
- HMB and at least one citrus flavonoid are administered to the subject at least once per day for at least 7 days, for at least 14 day, or for at least 30 days.
- the invention is directed to nutritional compositions comprising protein, fat, carbohydrate, HMB, and at least one citrus flavonoid.
- the nutritional compositions may be liquid nutritional compositions or powdered nutritional compositions.
- liquid nutritional composition as used herein, unless otherwise specified, encompasses all forms of liquid nutritional compositions, including emulsified liquids, concentrated liquids intended for dilution, for example, by addition of water, ready-to-drink liquids, and liquids that are reconstituted from powdered form by addition of liquid, for example, by addition of water or juice.
- the nutritional compositions are suitable for consumption by a human and, in a specific embodiment are in a form suitable for oral consumption.
- the nutritional compositions comprise an amount of HMB that is effective, in combination with the citrus flavonoid, to improve muscle energy production and/or muscle strength, and/or to reduce muscle loss.
- the nutritional compositions comprise HMB in an amount effective, in combination with the citrus flavonoid, to improve muscle energy production and/or muscle strength, and/or to reduce muscle loss, and, more specifically, to achieve one or more of these effects to an extent greater than that achieved with HMB alone.
- the nutritional compositions comprise HMB in an amount of about 0.1 to about 10 g per 237 ml serving, about 0.1 to about 5 g per 237 ml serving, about 0.5 to about 5 g per 237 ml serving, about 0.5 to about 3 g per 237 ml serving, or about 0.5 to about 1.5 g per 237 ml serving.
- the nutritional compositions comprise an amount of citrus flavonoid that is effective, in combination with the HMB, to improve muscle energy production and/or muscle strength, and/or to reduce muscle loss.
- the nutritional compositions comprise citrus flavonoid in an amount effective, in combination with the HMB, to achieve one or more of these effects to an extent greater than that achieved with citrus flavonoid alone.
- the nutritional compositions comprise citrus flavonoid in an amount of about 50 to about 1000 mg per 237 ml serving, about 50 to about 800 mg per 237 ml serving, about 50 to about 500 mg per 237 ml serving, about 50 to about 300 mg per 237 ml serving, about 100 to about 300 mg per 237 ml serving, or about 100 to about 500 mg per 237 ml serving.
- the protein which is contained in the nutritional composition may be any one or more proteins known for use in nutritional compositions.
- a wide variety of sources and types of protein can be used in the nutritional compositions.
- the source of protein may include, but is not limited to, intact, hydrolyzed, and partially hydrolyzed protein, which may be derived from any suitable source such as milk (e.g., casein, whey), animal (e.g., meat, fish), cereal (e.g., rice, brown rice, oat, barley, etc.), vegetable (e.g., soy, corn, pea, yellow pea, fava bean, chickpea, canola, potato, mung, ancient grains such as quinoa, amaranth, and chia, hemp, flax seed, etc.), nuts (e.g., almond and cashew), and combinations of two or more thereof.
- milk e.g., casein, whey
- animal e.g., meat, fish
- cereal e.g.
- the protein may also include one or a mixture of naturally occurring or synthetic amino acids (often described as free amino acids) and/or their metabolites, known for use in nutritional products, alone or in combination with the intact, hydrolyzed, and/or partially hydrolyzed proteins described herein.
- sources of protein which are suitable for use in the exemplary nutritional compositions described herein include, but are not limited to, whole egg powder, egg yolk powder, egg white powder, whey protein (including, but not limited to, whey protein components such as a-lactalbumin and p-lactoglobulin), whey protein concentrates, whey protein isolates, whey protein hydrolysates, acid caseins, casein protein isolates, sodium caseinates, calcium caseinates, potassium caseinates, casein hydrolysates, milk protein concentrates, milk protein isolates, milk protein hydrolysates, nonfat dry milk, condensed skim milk, whole cow’s milk, partially or completely defatted milk, coconut milk, soy protein concentrates, soy protein isolates, soy protein hydrolysates, pea protein concentrates, pea protein isolates, pea protein hydrolysates, rice protein concentrate, rice protein isolate, rice protein hydrolysate, barley rice protein, fava bean protein concentrate, fava bean
- the amount of the source of protein in the nutritional compositions can vary considerably depending upon, for example, the specific dietary needs of the intended user and/or the form of the composition, i.e., liquid or powder.
- the source of protein comprises from about 1 wt% to about 30 wt% of the nutritional composition.
- the source of protein comprises from about 2 wt% to about 25 wt% of the nutritional composition, including about 2 wt% to about 20 wt%, about 2 wt% to about 15 wt%, about 5 wt% to about 20 wt%, about 5 wt% to about 25 wt%, about 10 wt% to about 25 wt%, or about 5 wt% to about 15 wt% of the nutritional composition.
- the inventive nutritional compositions also include fat.
- fat refers to lipids, fats, oils, and combinations thereof.
- Sources of fat suitable for use in the nutritional composition include, but are not limited to, algal oil, canola oil, flaxseed oil, borage oil, safflower oil, high oleic safflower oil, high gamma-linolenic acid (GLA) safflower oil, corn oil, soy oil, sunflower oil, high oleic sunflower oil, cottonseed oil, coconut oil, fractionated coconut oil, medium chain triglycerides (MCT) oil, palm oil, palm kernel oil, palm olein, lecithin, and long chain polyunsaturated fatty acids such as docosahexanoic acid (DHA), arachidonic acid (ARA), docosapentaenoic acid (DPA), eicosapentaenoic acid (EPA), and combinations thereof
- DHA docosahexanoic
- the nutritional compositions comprise about 0.5 wt% to about 20 wt% of a source of fat.
- the source of fat comprises about 0.5 wt% to about 18 wt% of the nutritional composition, including about 0.5 wt% to about 15 wt%, about 0.5 wt% to about 10 wt%, about 0.5 wt% to about 5 wt%, about 2 wt% to about 8 wt%, about 2 wt% to about 10 wt%, about 5 wt% to about 15 wt%, or about 5 wt% to about 20 wt% of the nutritional composition.
- Sources of carbohydrates suitable for use in the nutritional compositions may be simple or complex, or variations, or combinations thereof.
- Various sources of carbohydrate may be used so long as the source is suitable for use in a nutritional composition and is otherwise compatible with any other selected ingredients or features present in the nutritional composition.
- Non-limiting examples of sources of carbohydrates suitable for use in the nutritional compositions include maltodextrin, hydrolyzed or modified starch, hydrolyzed or modified cornstarch, glucose polymers such as polydextrose and dextrins, corn syrup, corn syrup solids, rice-derived carbohydrates such as rice maltodextrin, brown rice mild powder and brown rice syrup, sucrose, glucose, fructose, lactose, high fructose corn syrup, honey, sugar alcohols (e.g., maltitol, erythritol, sorbitol), isomaltulose, sucromalt, pullulan, potato starch, corn starch, fructooligosaccharides, galactooligosaccharides, oat fiber, soy fiber, gum arabic, sodium carboxymethylcellulose, methylcellulose, guar gum, gellan gum, locust bean gum, konjac flour, hydroxypropyl methylcellulose, tragacanth gum, karaya gum, gum a
- the nutritional compositions may include any individual source of carbohydrate or a combination of two or more sources of carbohydrate.
- a source of carbohydrate is present in an amount from about 5 wt% to about 75 wt% of the nutritional compositions.
- the source of carbohydrate is present in an amount from about 5 wt% to about 70 wt% of the nutritional composition, including about 5 wt% to about 65 wt%, about 5 wt% to about 50 wt%, about 5 wt% to about 40 wt%, about 5 wt% to about 30 wt%, about 5 wt% to about 25 wt%, about 10 wt% to about 65 wt%, about 20 wt% to about 65 wt%, about 30 wt% to about 65 wt%, about 40 wt% to about 65 wt%, about 40 wt% to about 70 wt%, or about 15 wt% to about 25 wt%, of the nutritional composition.
- the source of carbohydrate comprises about 5 wt% to about 30 wt% of the nutritional composition.
- the carbohydrate comprises about 5 wt% to about 25 wt%, about 5 wt% to about 20 wt%, about 5 wt% to about 15 wt%, about 10 wt% to about 25 wt%, about 10 wt% to about 20 wt%, about 15 wt% to about 25 wt%, or about 15 wt% to about 30 wt% of the nutritional composition.
- the source of carbohydrate comprises about 25 wt% to about 75 wt% of the nutritional composition.
- the carbohydrate comprises about 30 wt% to about 70 wt%, about 35 wt% to about 65 wt%, about 40 wt% to about 65 wt%, about 40 wt% to about 70 wt%, about 50 wt% to about 70 wt%, or about 50 wt% to about 75 wt% of the nutritional composition.
- the relative amounts of the sources of protein, fat and carbohydrate in the nutritional compositions can vary considerably depending upon, for example, the specific dietary needs of the intended user and/or the form of the composition, i.e., liquid or powder.
- the nutritional compositions comprise a source of protein in an amount of about 2 wt % to about 25 wt %, a source of carbohydrate in an amount of about 5 wt % to about 75 wt %, and a source of fat in an amount of about 0.5 wt % to about 20 wt %, based on the weight of the nutritional composition.
- the nutritional composition comprises a source of protein in an amount of about 2 wt% to about 25 wt%, a source of carbohydrate in an amount of about 5 wt% to about 30 wt%, and a source of fat in an amount of about 0.5 wt% to about 10 wt%, based on the weight of the nutritional composition, and, more specifically, such composition is in liquid form.
- the nutritional composition comprises a source of protein in an amount of about 10 wt% to about 25 wt%, a source of carbohydrate in an amount of about 40 wt% to about 70 wt%, and a source of fat in an amount of about 5 wt% to about 20 wt%, based on the weight of the nutritional composition, and, more specifically, such composition is in powder form.
- the nutritional composition has a neutral pH, i.e., a pH of from about 6 to 8 or, more specifically, from about 6 to 7.5. In more specific embodiments, the nutritional composition has a pH of from about 6.5 to 7.2 or, more specifically, from about 6.8 to 7.1.
- the nutritional composition may further comprise one or more additional components that may modify the physical, chemical, aesthetic, or processing characteristics of the nutritional composition or serve as additional nutritional components.
- additional components include preservatives, emulsifying agents (e.g., lecithin), buffers, sweeteners including artificial sweeteners (e.g., saccharine, aspartame, acesulfame K, sucralose), colorants, flavorants, thickening agents, stabilizers, and so forth.
- the nutritional composition may further include vitamins or related nutrients, non-limiting examples of which include vitamin A, vitamin B12, vitamin C, vitamin D, vitamin K, thiamine, riboflavin, pyridoxine, niacin, folic acid, pantothenic acid, biotin, choline, inositol, salts and derivatives thereof, and combinations thereof.
- vitamins or related nutrients include vitamin A, vitamin B12, vitamin C, vitamin D, vitamin K, thiamine, riboflavin, pyridoxine, niacin, folic acid, pantothenic acid, biotin, choline, inositol, salts and derivatives thereof, and combinations thereof.
- Water soluble vitamins may be added in the form of a water-soluble vitamin (WSV) premix and/or oil-soluble vitamins may be added in one or more oil carriers as desired.
- WSV water-soluble vitamin
- the nutritional composition may further include one or more minerals, non-limiting examples of which include calcium, phosphorus, magnesium, zinc, manganese, sodium, potassium, molybdenum, chromium, chloride, and combinations thereof.
- the nutritional composition may further include one or more probiotics.
- probiotic refers to a microorganism such as a bacteria or yeast that survives the digestive process to confer a health benefit to the subject. Examples of probiotics that can be included in the nutritional compositions, either alone or in combination, include, but are not limited to, Bifidobacterium (B.), such as B. breve, B. infantis, B. lactis, B.
- Lactobacillus such as L. rhamnosus, L. acidophilus, L. fermentum, L. reuteri, Streptococcus thermophilus, Akkermansia, Bacteroides, Enterococcus, Eubacterium, Fecalibacterium, Roseburia, and/or Saccharomyces.
- the nutritional compositions may be formed using any techniques known in the art.
- the nutritional compositions may be formed by (a) preparing an aqueous solution comprising protein and carbohydrate; (b) preparing an oil blend comprising fat and oilsoluble components; and (c) mixing together the aqueous solution and the oil blend to form an emulsified liquid nutritional composition.
- the HMB and citrus flavonoid may be added at any time as desired in the process, for example, to the aqueous solution or to the emulsified blend.
- the compositions may be spray-dried or otherwise dried, if a powder product is desired.
- a powder product can be formed by dry blending ingredients.
- the nutritional compositions are subjected to a heat treatment which provides sterilization sufficient to maintain microbiological stability of the compositions over a desired shelf-life.
- the present example evaluated the effect of HMB, a flavonoid-containing citrus extract, hesperidin and hesperetin each individually, and the effect of combinations of HMB with each of the flavonoid-containing citrus extract, hesperidin, and hesperetin, respectively, on muscle mitochondria dysfunction caused by exposure to the glucocorticoid dexamethasone (DEX) using the well-established mouse muscle cell line, C2C12 myotubes.
- Dexamethasone is known to trigger protein degradation in muscle and is used to induce mitochondrial dysfunction as encountered in aging and/or hypercatabolic conditions.
- C2C12 myoblasts were grown in high-glucose Dulbecco's modified eagle medium (DMEM) supplemented with 10% fetal bovine serum, 4 mM glutamine, 100 units/ml penicillin, and 0.1 mg/ml streptomycin at 37°C in humidified 95% air with 5% CO2. After reaching 90% confluence, the cells were induced to differentiate in differentiation media of high-glucose DMEM supplemented with 2% horse serum.
- DMEM Dulbecco's modified eagle medium
- HMB HMB
- flavonoid-containing citrus extract 20 pM
- hesperidin 5 pM
- hesperetin 0.1 pM
- HMB (50 pM) and hesperetin for 24 hours.
- OCR oxygen consumption rate
- the test employs sequential addition of oligomycin (1 pM), proton ionophore carbonylcyanide-p trifluromethoxyphenylhydrazone (FCCP, 0.5 pM) and rotenone and antimycin A (0.5 pM), and measures the key parameters of mitochondrial respiration including spare respiratory capacity (SRC).
- SRC spare respiratory capacity
- the terms “reserve respiratory capacity” and “spare respiratory capacity” are used to describe the amount of extra ATP that can be produced by oxidative phosphorylation in case of a sudden increase in energy demand on the cell. This is especially needed during hypercatabolic and inflammatory states that lead to muscle atrophy. These respiratory parameters of mitochondrial function were calculated by the equipment’s software.
- the negative control DEX-treated (5 pM) C2C12 myotubes showed a general impairment in SRC, specifically a 48% reduction in SRC, as compared with the positive Control group which did not have any HMB, citrus flavonoid, or DEX treatment.
- C2C12 grown in presence of the combination of HMB (50 pM) and flavonoid-containing citrus extract (20 pM) showed a significant increase of SRC of about 55 % with respect to the DEX-treated negative control. Additionally, the increase in SRC was higher than the effect observed with each one of the individual ingredients (+21%). Similar results were observed when cells were grown in presence of the combination of HMB (50 pM) and hesperidin (5 pM) (Fig. 2), showing an increase in SRC of about +50% with respect to DEX- treated cells and about +23% in comparison with the effects observed with each of the individual ingredients.
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WO2010068696A1 (en) * | 2008-12-09 | 2010-06-17 | Metabolic Technologies, Inc. | Nutritional intervention for improving muscular function and strength |
WO2015199169A1 (en) * | 2014-06-27 | 2015-12-30 | 国立大学法人九州大学 | Catechin function enhancement method |
EP3132692A1 (en) * | 2015-03-24 | 2017-02-22 | Biosens Croatia | Compositions comprising small molecular inhibitors suitable to inhibit and stimulate signaling pathways in a manner leading to prevention of muscle atrophy |
JP6071092B2 (en) * | 2016-02-05 | 2017-02-01 | ポッカサッポロフード&ビバレッジ株式会社 | Disuse muscular atrophy inhibitor, food / beverage composition for disuse muscular atrophy control, and method for producing food / beverage composition for disuse muscular atrophy control |
KR101809379B1 (en) * | 2016-10-13 | 2017-12-14 | 연세대학교 산학협력단 | Composition comprising Diosmin or as active ingredients for Preventing or treating muscle disease |
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2022
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- 2022-01-21 WO PCT/US2022/013286 patent/WO2022164722A1/en active Application Filing
- 2022-01-21 CA CA3206564A patent/CA3206564A1/en active Pending
- 2022-01-21 JP JP2023545898A patent/JP2024506835A/en active Pending
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