EP2152280A1 - Branched-chain amino acid composition for improving skeletal muscle protein metabolism - Google Patents

Branched-chain amino acid composition for improving skeletal muscle protein metabolism

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Publication number
EP2152280A1
EP2152280A1 EP07719718A EP07719718A EP2152280A1 EP 2152280 A1 EP2152280 A1 EP 2152280A1 EP 07719718 A EP07719718 A EP 07719718A EP 07719718 A EP07719718 A EP 07719718A EP 2152280 A1 EP2152280 A1 EP 2152280A1
Authority
EP
European Patent Office
Prior art keywords
composition
skeletal muscle
acts
derivatives
branched
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Withdrawn
Application number
EP07719718A
Other languages
German (de)
French (fr)
Inventor
Ken Clement
Shan Chaudhuri
Michele Molino
Phil Apong
Jason Peters
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Northern Innovations and Formulations Corp
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Northern Innovations and Formulations Corp
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Publication date
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Publication of EP2152280A1 publication Critical patent/EP2152280A1/en
Withdrawn legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/19—Acanthaceae (Acanthus family)
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/18—Peptides; Protein hydrolysates
    • 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
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • 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
    • A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
    • 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
    • A61P21/06—Anabolic agents
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present invention relates to a nutritional composition for improving the protein metabolism of skeletal muscles. A method of the same is also provided.
  • Body composition including muscle, is influenced both by genetic factors and environmental stimuli. Genetic factors are typically difficult, if not impossible to alter through intervention. Environmental factors however are routinely manipulated and important environmental factors that effect muscle metabolism, such as food intake and exercise, effect muscle metabolism within hours of stimulation A Gene and protein expression patterns change in response to these stimuli. These changes result in muscle adaptations such as muscle atrophy (loss) via muscle protein catabolism (breakdown) or muscle hypertrophy (increase) via muscle protein accretion. These opposing actions are not mutually exclusive and the determination of muscle loss or gain is the net effect of both positive and negative factors governing muscle development.
  • Exercise is a major stimulus of skeletal muscle growth. During several hours post-exercise there are dynamic changes in the rates of both skeletal muscle synthesis and breakdown. The consumption of specific dietary components is known to further influence the response of skeletal muscle to exercise.
  • the main component of food that is known to stimulate increased muscle protein synthesis is amino acids (Rennie MJ. Body maintenance and repair: how food and exercise keep the musculoskeletal system in good shape. Exp Physiol. 2005 Jul;90(4):427-36).
  • Increased levels of circulating essential amino acids have been shown to stimulate protein synthesis (Smith K, Reynolds N, Downie S, Patel A, Rennie MJ. Effects of flooding amino acids on incorporation of labeled amino acids into human muscle protein. Am J Physiol.
  • NF- ⁇ B Nuclear Factor kappa B
  • the present invention comprises one or more branched-chain amino acids or derivatives thereof, a plant extract for attenuating NF-/cB signaling, and y-butyrobetaine or derivative thereof for inducing vasodilation.
  • Administration of the composition of present invention provides a method for improving the skeletal muscle protein metabolism of an individual.
  • the present invention is directed towards improving skeletal muscle protein metabolism, both in terms of promoting increased muscle protein accrual via increased protein synthesis and in terms of reducing the breakdown of skeletal muscle protein.
  • the present invention is particularly useful for individuals engaged in regular intense physical activity who wish to gain lean muscle mass and size or minimize muscle loss.
  • a nutritional composition comprised of BCAAs.
  • the BCAAs employed may be selected from Leucine, lsoleucine and Valine or derivatives of each thereof.
  • a nutritional composition comprised of BCAAs and at least one ingredient known to attenuate NF-/cB signaling is provided.
  • the ingredient known to attenuate NF-/cB signaling is an extract of Andrographis paniculata.
  • a nutritional composition comprised of BCAAs, at least one ingredient known to attenuate NF- ⁇ B signaling and at least one ingredient known to increase vasodilation via increased levels of nitric oxide is provided.
  • the ingredient known to increase vasodilation via increased levels of nitric oxide is ⁇ -butyrobetaine or derivatives thereof.
  • a nutritional composition comprised of Leucine, lsoleucine and Valine or derivatives of each thereof, an extract of Andrographis paniculata and ⁇ -butyrobetaine or derivatives thereof is provided for improving skeletal muscle protein metabolism.
  • BCAAs The branched-chain amino acids
  • BCAAs consist of Leucine, lsoleucine and Valine. BCAAs are considered essential since humans cannot synthesis them - they must be obtained from the diet - despite their importance. They are not only used in the synthesis of other amino acids but are important in the regulation of the anabolic process in skeletal muscle. BCAAs not only increase the rate of protein synthesis but also inhibit protein degradation (Matthews DE. Observations of branched-chain amino acid administration in humans. J Nutr. 2005 Jun;135(6 Suppl):1580S-4S).
  • the nutritional supplement comprises BCAAs or derivatives thereof.
  • the amount of BCAAs or derivatives thereof in a serving of the nutritional supplement is from about 0.7 g to about 10.5 g.
  • the preferred embodiment of the present invention comprises the BCAAs Leucine, lsoleucine and Valine or derivatives of each thereof in the following amounts.
  • a serving of the nutritional supplement comprises Leucine or derivatives thereof from about 0.5 g to about 8.0 g.
  • a serving of the nutritional supplement comprises lsoleucine or derivatives thereof from about 0.07 g to about 3.0 g.
  • a serving of the nutritional supplement comprises Valine or derivatives thereof from about 0.1 g to about 3.5 g.
  • the ratio of lsoleucine to Leucine to Valine in the nutritional composition is about 1 to 2.3 to 1.2.
  • Andrographis paniculata is a medicinal herb used traditionally throughout Asia used to treat a number of conditions.
  • One of the active ingredients of Andrographis paniculata extract is the diterpene, andrographolide.
  • Andrographolide is known to inhibit the activity of NF- ⁇ B by interfering with the binding of NF-/cB to DNA (Hidalgo MA, Romero A, Figueroa J, Cortes P, Concha II, Hancke JL, Burgos RA. Andrographolide interferes with binding to nuclear factor-/cB to DNA in HL-60-derived neutrophilic cells. Br J Pharmacol. 2005 Mar;144(5):680-6).
  • the nutritional supplement comprises an extract of Andrographis paniculata.
  • the amount of Andrographis paniculata extract in a serving of the nutritional supplement is from about 0.05 g to about 1 g.
  • the preferred amount of Andrographis paniculata extract in a serving of the nutritional supplement is about 0.1 g.
  • the present invention may also include additional components known to attenuate NF- ⁇ B-mediated signaling to promote the efficacy of the composition.
  • the nutritional supplement may further comprise Diferuloylmethane (Curcumin) (Singh S, Aggarwal BB.
  • K-butyrobetaine is an intermediate in carnitine biosynthesis in mammals. It is synthesized, from trimethyl lysine, in almost all cell types and then excreted into the blood to be reabsorbed by the kidney and liver. After reabsorption, ⁇ -butyrobetaine is converted to carnitine by y-butyrobetaine dioxygenase. This conversion to carnitine is extremely efficient, , thus presence of ⁇ -butyrobetaine in urine is very small (Vaz FM, Wanders RJA. Carnitine biosynthesis in mammals. Biochem J. 2002;361 :417-429).
  • vasodilating activities were attributed to increases in nitric oxide concentrations in blood.
  • the nutritional supplement comprises ⁇ -butyrobetaine or derivatives thereof.
  • the amount of ⁇ -butyrobetaine or derivatives thereof in a serving of the nutritional supplement is from about 0.01 g to about 1 g.
  • the preferred amount of y- butyrobetaine or derivatives thereof in a serving of the nutritional supplement is about 0.2 g.
  • the components of the present invention will act synergistically and simultaneously to promote improved protein metabolism in skeletal muscles.
  • the BCAAs or derivatives thereof will act to increase skeletal muscle protein synthesis while decreasing skeletal muscle protein breakdown; the Andrographis paniculata extract and other like-directed components will act to attenuate inflammatory signals mediated by NF-/d3 resulting from intense exercise; the of ⁇ -butyrobetaine or derivatives thereof will act to vasodilate blood vessels via increase nitric oxide to facilitate the delivery of nutrients to active or recovering skeletal muscles.
  • the nutritional supplement may be consumed in any form.
  • the dosage form of the nutritional supplement may be provided as, e.g., a powder beverage mix, a liquid beverage, a ready-to-eat bar or drink product, a capsule, a liquid capsule, a tablet, a caplet, or as a dietary gel.
  • the preferred dosage form of the present invention is a caplet.
  • the dosage form of the nutritional supplement may be provided in accordance with customary processing techniques for herbal and nutritional supplements in any of the forms mentioned above.
  • the nutritional supplement set forth in the example embodiment herein may contain any appropriate number and type of excipients, as is well known in the art.
  • specific excipients as well as specific dosage formats may be utilized to achieve specific controlled-release of active ingredients.
  • Such formats include but are not limited to quick-release, timed-release, slow-release and delayed-release.
  • the present nutritional composition or those similarly envisioned by one of skill in the art, may be utilized in methods to improve skeletal muscle protein synthesis. As such, the present invention may be utilized as a sole means of improving skeletal muscle protein synthesis or in combination with other like-directed compounds.
  • one serving is to be taken 45 minutes before exercise and the second serving to be taken 30 minutes after exercise.
  • one serving is to be taken in the morning and the second serving to be taken in the afternoon.
  • One serving of the nutritional supplement contains the following: about 1.75 g L-Leucine, about 0.001 g L-Leucine Ethyl Ester HCL, about 0.001 g N-Acetyl L-Leucine, about 0.93 g L-Valine, about 0.001 g L-Valine Ethyl Ester, about 0.001 g N-Acetyl L-Valine, about 0.77 g L-lsoleucine, about 0.001 g L-lsoleucine Ethyl Ester, about 0.001 g N-Acetyl L-lsoleucine, about 0.25 g Diferuloylmethane, about 0.10 g Andrographis paniculata extract (15% Andrographolide), and about 0.05 g Pyruvic Acid Ethyl Ester (ethyl pyruvate).
  • Example 2 Example 2
  • one serving is to be taken 45 minutes before exercise and the second serving to be taken 30 minutes after exercise.
  • one serving is to be taken in the morning and the second serving to be taken in the afternoon.
  • One serving of the nutritional supplement contains the following: about 3.55 g L-Leucine, about 0.001 g L-Leucine Ethyl Ester HCL, about 0.001 g N-Acetyl L-Leucine, about 1.85 g L-Valine, about 0.001 g L-Valine Ethyl Ester, about 0.001 g N-Acetyl L-Valine, about 1.54 g L-lsoleucine, about 0.001 g L-lsoleucine Ethyl Ester, about 0.001 g N-Acetyl L-lsoleucine, about 0.25 g Diferuloylmethane, about 0.1O g Andrographis paniculata extract, and about 0.05 g Pyruvic Acid Ethyl Ester (ethyl pyruvate).

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Abstract

The present invention relates to compositions and methods for improving skeletal muscle protein metabolism through encouraging skeletal muscle protein synthesis, reducing skeletal muscle protein degradation, and attenuating inflammatory signalling in exercising muscle. The compositions of the present invention comprise branched-chain amino acids, a plant extract that attenuates NF-ϰB activity and γ-butyrobetaine, and optionally, ethyl pyruvate or diferuloylmethane.

Description

BRANCHED-CHAIN AMINO ACID COMPOSITION FOR IMPROVING SKELETAL MUSCLE PROTEIN METABOLISM
Field of the Invention
The present invention relates to a nutritional composition for improving the protein metabolism of skeletal muscles. A method of the same is also provided.
Background of the Invention
Body composition, including muscle, is influenced both by genetic factors and environmental stimuli. Genetic factors are typically difficult, if not impossible to alter through intervention. Environmental factors however are routinely manipulated and important environmental factors that effect muscle metabolism, such as food intake and exercise, effect muscle metabolism within hours of stimulation A Gene and protein expression patterns change in response to these stimuli. These changes result in muscle adaptations such as muscle atrophy (loss) via muscle protein catabolism (breakdown) or muscle hypertrophy (increase) via muscle protein accretion. These opposing actions are not mutually exclusive and the determination of muscle loss or gain is the net effect of both positive and negative factors governing muscle development.
Exercise is a major stimulus of skeletal muscle growth. During several hours post-exercise there are dynamic changes in the rates of both skeletal muscle synthesis and breakdown. The consumption of specific dietary components is known to further influence the response of skeletal muscle to exercise. The main component of food that is known to stimulate increased muscle protein synthesis is amino acids (Rennie MJ. Body maintenance and repair: how food and exercise keep the musculoskeletal system in good shape. Exp Physiol. 2005 Jul;90(4):427-36). Increased levels of circulating essential amino acids have been shown to stimulate protein synthesis (Smith K, Reynolds N, Downie S, Patel A, Rennie MJ. Effects of flooding amino acids on incorporation of labeled amino acids into human muscle protein. Am J Physiol. 1998 Jul;275(1 Pt 1 ):E73-8). Exercise stimulates inflammatory pathways which contribute to anabolic responses. However, excessive activation of inflammatory signaling molecules such as Nuclear Factor kappa B (NF-κB) has been implicated in several disease states involving loss or weakening of muscle (Kramer HF, Goodyear LJ. Exercise, MAPK, and NF-{kappa}B Signaling in Skeletal Muscle. J Appl Physiol. 2007 Feb 15). In these situations skeletal muscle protein breakdown exceeds protein synthesis.
It would therefore be advantageous for an individual concerned with maintaining or increasing lean skeletal muscle mass to consume a nutritional composition directed at improving skeletal muscle metabolism, to encourage skeletal muscle protein synthesis while minimizing skeletal muscle protein breakdown. Summary of the Invention
The foregoing needs and other needs and objectives that will become apparent for the following description are achieved in the present invention, which comprises one or more branched-chain amino acids or derivatives thereof, a plant extract for attenuating NF-/cB signaling, and y-butyrobetaine or derivative thereof for inducing vasodilation. Administration of the composition of present invention provides a method for improving the skeletal muscle protein metabolism of an individual. Detailed Description of the Invention
In the following description, for the purposes of explanations, numerous specific details are set forth in order to provide a thorough understanding of the present invention. It will be apparent, however, to one of ordinary skill in the art that the present invention may be practiced without these specific details.
The present invention is directed towards improving skeletal muscle protein metabolism, both in terms of promoting increased muscle protein accrual via increased protein synthesis and in terms of reducing the breakdown of skeletal muscle protein. The present invention is particularly useful for individuals engaged in regular intense physical activity who wish to gain lean muscle mass and size or minimize muscle loss.
In an embodiment of the present invention, a nutritional composition comprised of BCAAs is provided. The BCAAs employed may be selected from Leucine, lsoleucine and Valine or derivatives of each thereof. In an embodiment of the present invention, a nutritional composition comprised of BCAAs and at least one ingredient known to attenuate NF-/cB signaling is provided. In a preferred embodiment the ingredient known to attenuate NF-/cB signaling is an extract of Andrographis paniculata.
In an embodiment of the present invention, a nutritional composition comprised of BCAAs, at least one ingredient known to attenuate NF-κB signaling and at least one ingredient known to increase vasodilation via increased levels of nitric oxide is provided. In a preferred embodiment the ingredient known to increase vasodilation via increased levels of nitric oxide is κ-butyrobetaine or derivatives thereof. In a preferred embodiment of the present invention, a nutritional composition comprised of Leucine, lsoleucine and Valine or derivatives of each thereof, an extract of Andrographis paniculata and κ-butyrobetaine or derivatives thereof is provided for improving skeletal muscle protein metabolism. Branched-Chain Amino Acids
The branched-chain amino acids (BCAAs) consist of Leucine, lsoleucine and Valine. BCAAs are considered essential since humans cannot synthesis them - they must be obtained from the diet - despite their importance. They are not only used in the synthesis of other amino acids but are important in the regulation of the anabolic process in skeletal muscle. BCAAs not only increase the rate of protein synthesis but also inhibit protein degradation (Matthews DE. Observations of branched-chain amino acid administration in humans. J Nutr. 2005 Jun;135(6 Suppl):1580S-4S).
In various embodiment of the present invention detailed in examples 1 and 2 below, the nutritional supplement comprises BCAAs or derivatives thereof. The amount of BCAAs or derivatives thereof in a serving of the nutritional supplement is from about 0.7 g to about 10.5 g.
The preferred embodiment of the present invention comprises the BCAAs Leucine, lsoleucine and Valine or derivatives of each thereof in the following amounts. A serving of the nutritional supplement comprises Leucine or derivatives thereof from about 0.5 g to about 8.0 g. A serving of the nutritional supplement comprises lsoleucine or derivatives thereof from about 0.07 g to about 3.0 g. A serving of the nutritional supplement comprises Valine or derivatives thereof from about 0.1 g to about 3.5 g. Furthermore, in the preferred embodiment of the present invention, the ratio of lsoleucine to Leucine to Valine in the nutritional composition is about 1 to 2.3 to 1.2.
Andrographis paniculata
Andrographis paniculata is a medicinal herb used traditionally throughout Asia used to treat a number of conditions. One of the active ingredients of Andrographis paniculata extract is the diterpene, andrographolide. (Shen YC, Chen CF, Chiou WF. Andrographolide prevents oxygen radical production by human neutrophils: possible mechanism(s) involved in its anti-inflammatory effect. Br J Pharmacol. 2002 Jan;135(2):399-406). Andrographolide is known to inhibit the activity of NF-κB by interfering with the binding of NF-/cB to DNA (Hidalgo MA, Romero A, Figueroa J, Cortes P, Concha II, Hancke JL, Burgos RA. Andrographolide interferes with binding to nuclear factor-/cB to DNA in HL-60-derived neutrophilic cells. Br J Pharmacol. 2005 Mar;144(5):680-6).
In various embodiment of the present invention detailed in examples 1 and 2 below, the nutritional supplement comprises an extract of Andrographis paniculata. The amount of Andrographis paniculata extract in a serving of the nutritional supplement is from about 0.05 g to about 1 g. The preferred amount of Andrographis paniculata extract in a serving of the nutritional supplement is about 0.1 g. In additional embodiments, the present invention may also include additional components known to attenuate NF-^B-mediated signaling to promote the efficacy of the composition. For example, the nutritional supplement may further comprise Diferuloylmethane (Curcumin) (Singh S, Aggarwal BB. Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane) [corrected] J Biol Chem. 1995 Oct 20;270(42):24995-5000. Erratum in: J Biol Chem 1995 Dec 15;270(50):30235) or Ethyl pyruvate (Pyruvic Acid Ethyl Ester) (Das UN. Pyruvate is an endogenous anti-inflammatory and anti-oxidant molecule. Med Sci Monit. 2006 May;12(5):RA79-84). Ethyl pyruvate also has the benefit of providing an energy substrate beta-oxidation in the mit K-butyrobetaine
K-butyrobetaine is an intermediate in carnitine biosynthesis in mammals. It is synthesized, from trimethyl lysine, in almost all cell types and then excreted into the blood to be reabsorbed by the kidney and liver. After reabsorption, κ-butyrobetaine is converted to carnitine by y-butyrobetaine dioxygenase. This conversion to carnitine is extremely efficient, , thus presence of κ-butyrobetaine in urine is very small (Vaz FM, Wanders RJA. Carnitine biosynthesis in mammals. Biochem J. 2002;361 :417-429).
The administration of y-butyrobetaine to rats (Sjakste N, Kleschyov JL, Baumane L, Dzintare M, Meirena D, Sjakste J, Sydow K, Munzel T, Kalvinsh I.
Endothelium- and nitric oxide-dependent vasorelaxing activities of gamma- butyrobetaine esters: possible link to the antiischemic activities of mildronate. Eur J
Pharmacol. 2004 JuI 8; 495(1 ):67-73 (Abstract)), provides vasodilating activities.
These vasodilating activities were attributed to increases in nitric oxide concentrations in blood.
In various embodiment of the present invention detailed in examples 1 and 2 below, the nutritional supplement comprises κ-butyrobetaine or derivatives thereof. The amount of κ-butyrobetaine or derivatives thereof in a serving of the nutritional supplement is from about 0.01 g to about 1 g. The preferred amount of y- butyrobetaine or derivatives thereof in a serving of the nutritional supplement is about 0.2 g.
Not wishing to be bound by theory, it is believed that the components of the present invention will act synergistically and simultaneously to promote improved protein metabolism in skeletal muscles. The BCAAs or derivatives thereof will act to increase skeletal muscle protein synthesis while decreasing skeletal muscle protein breakdown; the Andrographis paniculata extract and other like-directed components will act to attenuate inflammatory signals mediated by NF-/d3 resulting from intense exercise; the of κ-butyrobetaine or derivatives thereof will act to vasodilate blood vessels via increase nitric oxide to facilitate the delivery of nutrients to active or recovering skeletal muscles.
According to various embodiments of the present invention, the nutritional supplement may be consumed in any form. For instance, the dosage form of the nutritional supplement may be provided as, e.g., a powder beverage mix, a liquid beverage, a ready-to-eat bar or drink product, a capsule, a liquid capsule, a tablet, a caplet, or as a dietary gel. The preferred dosage form of the present invention is a caplet.
Furthermore, the dosage form of the nutritional supplement may be provided in accordance with customary processing techniques for herbal and nutritional supplements in any of the forms mentioned above. Additionally, the nutritional supplement set forth in the example embodiment herein may contain any appropriate number and type of excipients, as is well known in the art.
The inclusion of specific excipients, as well as specific dosage formats may be utilized to achieve specific controlled-release of active ingredients. Such formats include but are not limited to quick-release, timed-release, slow-release and delayed-release.
The present nutritional composition or those similarly envisioned by one of skill in the art, may be utilized in methods to improve skeletal muscle protein synthesis. As such, the present invention may be utilized as a sole means of improving skeletal muscle protein synthesis or in combination with other like-directed compounds.
Although the following examples illustrate the practice of the present invention in two of its embodiments, the examples should not be construed as limiting the scope of the invention. Other embodiments will be apparent to one of skill in the art from consideration of the specifications and examples.
Examples
Example 1
A nutritional supplement in the form of caplets to be consumed twice daily. On workout days, one serving is to be taken 45 minutes before exercise and the second serving to be taken 30 minutes after exercise. On non-workout days, one serving is to be taken in the morning and the second serving to be taken in the afternoon. One serving of the nutritional supplement contains the following: about 1.75 g L-Leucine, about 0.001 g L-Leucine Ethyl Ester HCL, about 0.001 g N-Acetyl L-Leucine, about 0.93 g L-Valine, about 0.001 g L-Valine Ethyl Ester, about 0.001 g N-Acetyl L-Valine, about 0.77 g L-lsoleucine, about 0.001 g L-lsoleucine Ethyl Ester, about 0.001 g N-Acetyl L-lsoleucine, about 0.25 g Diferuloylmethane, about 0.10 g Andrographis paniculata extract (15% Andrographolide), and about 0.05 g Pyruvic Acid Ethyl Ester (ethyl pyruvate). Example 2
A nutritional supplement in the form of caplets to be consumed twice daily. On workout days, one serving is to be taken 45 minutes before exercise and the second serving to be taken 30 minutes after exercise. On non-workout days, one serving is to be taken in the morning and the second serving to be taken in the afternoon. One serving of the nutritional supplement contains the following: about 3.55 g L-Leucine, about 0.001 g L-Leucine Ethyl Ester HCL, about 0.001 g N-Acetyl L-Leucine, about 1.85 g L-Valine, about 0.001 g L-Valine Ethyl Ester, about 0.001 g N-Acetyl L-Valine, about 1.54 g L-lsoleucine, about 0.001 g L-lsoleucine Ethyl Ester, about 0.001 g N-Acetyl L-lsoleucine, about 0.25 g Diferuloylmethane, about 0.1O g Andrographis paniculata extract, and about 0.05 g Pyruvic Acid Ethyl Ester (ethyl pyruvate).
Extensions and Alternatives
In the foregoing specification, the invention has been described with a specific embodiment thereof, however, it will be evident that various modifications and changes may be made thereto without departing from the broader spirit and scope of the invention.

Claims

ClaimsWhat is claimed:
1. A nutritional composition comprising at least one or more branched-chain amino acids or derivatives thereof, a plant extract, and
K-butyrobetaine or derivative thereof wherein said branched-chain amino acid acts to activate skeletal muscle protein synthesis and inhibit skeletal muscle protein degradation, said plant extract acts to attenuate NF-/cB activity, and said /-butyrobetaine or derivative thereof acts to increase vasodilation via increased levels of nitric oxide in a mammal.
2. The composition of claim 1 wherein the branched-chain amino acid is selected from, but not limited to, Leucine or derivatives thereof, Valine or derivatives thereof, and lsoleucine or derivatives thereof.
3. The composition of claim 1 wherein said plant extract is an extract of
Andrographis paniculata.
4. The composition of claim 1 , further comprising an effective amount of ethyl pyruvate; wherein said ethyl pyruvate acts to increase substrate availability for mitochondrial beta-oxidation.
5. The composition of claim 1 , further comprising an effective amount of diferuloylmethane; wherein said diferuloylmethane acts to attenuate NF-/cB activity.
6. A nutritional composition comprising an effective amount of at least one branched-chain amino acid, and effective amount of an extract of Andrographis paniculata, and an effective amount of y-butyrobetaine or derivative thereof.
7. The composition of claim 6 wherein the branched-chain amino acid is selected from , but not limited to, Leucine or derivatives thereof, Valine or derivatives thereof, and lsoleucine or derivatives thereof.
8. The composition of claim 7 wherein said branched-chain amino acid acts to activate skeletal muscle protein synthesis or inhibit skeletal muscle protein degradation.
9. The composition of claim 6 wherein the extract of Andrographis paniculata acts to attenuate NF-/cB activity.
10. The composition of claim 6 wherein the κ-butyrobetaine or derivative thereof acts to increase vasodilation via increased levels of nitric oxide.
11. The composition of claim 6, further comprising an effective amount of ethyl pyruvate; wherein said ethyl pyruvate acts to increase substrate availability for mitochondrial beta-oxidation.
12. The composition of claim 6, further comprising an effective amount of diferuloylmethane; wherein said diferuloylmethane acts to NF-κB activity.
EP07719718A 2007-05-08 2007-05-08 Branched-chain amino acid composition for improving skeletal muscle protein metabolism Withdrawn EP2152280A1 (en)

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CN103750143A (en) * 2014-01-21 2014-04-30 中国人民解放军第三军医大学 Anti-hypoxia and anti-fatigue energy composition and application thereof

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EP3652743A1 (en) * 2017-09-07 2020-05-20 Liposcience, Inc. Multi-parameter metabolic vulnerability index evaluations
CN110693877B (en) * 2019-10-21 2022-12-02 中国中医科学院广安门医院 Application of andrographolide in preparing medicine for preventing or/and treating sarcopenia

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103750143A (en) * 2014-01-21 2014-04-30 中国人民解放军第三军医大学 Anti-hypoxia and anti-fatigue energy composition and application thereof

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