WO2011064373A1 - Method of enhancing muscle protein synthesis - Google Patents

Method of enhancing muscle protein synthesis Download PDF

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Publication number
WO2011064373A1
WO2011064373A1 PCT/EP2010/068439 EP2010068439W WO2011064373A1 WO 2011064373 A1 WO2011064373 A1 WO 2011064373A1 EP 2010068439 W EP2010068439 W EP 2010068439W WO 2011064373 A1 WO2011064373 A1 WO 2011064373A1
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WO
WIPO (PCT)
Prior art keywords
protein
training
exercise
essential amino
amino acids
Prior art date
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Ceased
Application number
PCT/EP2010/068439
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English (en)
French (fr)
Inventor
Daniel Ryan Moore
Eric Zaltas
John Alan Hawley
Louise Mary Burke
Trent Stellingwerff
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Nestec SA
Original Assignee
Nestec SA
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Nestec SA filed Critical Nestec SA
Priority to NZ600094A priority Critical patent/NZ600094A/en
Priority to CN201080053149.6A priority patent/CN102665445B/zh
Priority to IN4085DEN2012 priority patent/IN2012DN04085A/en
Priority to JP2012540457A priority patent/JP5810429B2/ja
Priority to HK13102989.4A priority patent/HK1175664B/xx
Priority to MX2012005646A priority patent/MX2012005646A/es
Priority to RU2012127126/13A priority patent/RU2503269C1/ru
Priority to CA2781764A priority patent/CA2781764A1/en
Priority to PH1/2012/500875A priority patent/PH12012500875A1/en
Priority to AU2010323089A priority patent/AU2010323089B2/en
Priority to BR112012012811A priority patent/BR112012012811A2/pt
Priority to US13/511,854 priority patent/US20130203645A1/en
Publication of WO2011064373A1 publication Critical patent/WO2011064373A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/02Peptides of undefined number of amino acids; Derivatives thereof
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L29/00Foods or foodstuffs containing additives; Preparation or treatment thereof
    • A23L29/30Foods or foodstuffs containing additives; Preparation or treatment thereof containing carbohydrate syrups; containing sugars; containing sugar alcohols, e.g. xylitol; containing starch hydrolysates, e.g. dextrin
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17Amino acids, peptides or proteins
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17Amino acids, peptides or proteins
    • A23L33/175Amino acids
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/40Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/195Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197Carboxylic 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00Drugs for disorders of the muscular or neuromuscular system
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/125Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates

Definitions

  • the present invention relates to a method and program of improving muscle protein synthesis.
  • the invention relates to the improvement of muscle protein synthesis in an individual doing physical exercise.
  • exercise training regimes There are three main different types of exercise training regimes which include: 1) resistance exercise 2) anaerobic or repeated sprint type exercise and 3) endurance exercise. Each of these exercise training regimes features a divergent training response.
  • Endurance training is characterized by individuals doing low-intensity training over prolonged periods (e.g. > 15min) .
  • the energy system represented for endurance training includes the aerobic system, which primarily uses aerobic metabolism of fats and carbohydrates to produce the required energy within the mitochondria when ample oxygen is present.
  • the primary adaptations include increased muscle glycogen stores and glycogen sparing at sub-maximal workloads via increased fat oxidation, enhanced lactate kinetics and morphological alterations, including greater type I fibre per muscle area, and increased capillary and mitochondrial density (Holloszy JO, and Coyle EF. Adaptations of skeletal muscle to endurance exercise and their metabolic consequences. J Appl Physiol 56: 831-838, 1984.
  • the present invention seeks to address the above-described problems.
  • the invention also aims at other objects and particularly the solution of other problems as will appear in the rest of the present description.
  • the invention provides method of enhancing muscle protein synthesis following physical exertion comprising administering to a human a composition comprising protein or essential amino acids and carbohydrates 30 minutes or less prior to, during, or within 30 minutes after running repeated sprints, such as normally found with the majority of team sports. It has surprisingly been found that the addition of protein or essential amino acids with repeated sprint exercise has the capacity of enhancing myofibrillar protein synthesis.
  • Myofibrillar protein is the specific protein responsible for muscle hypertrophy (growth) .
  • Physical exercise provides a stimulus to the body that triggers a cascade of molecular signals that lead to changes in gene expression and the synthesis of proteins specific to the exercise stimulus.
  • the physical adaptation that results from chronic training is believed to be a direct result of the accumulation of these proteins after multiple bouts of acute exercise.
  • a clear beneficial effect is shown on anabolic signalling and muscle protein synthesis following repeated sprint based exercise with nutrients provisions. Recommendations are to take protein and carbohydrate in close temporary timing to strenuous training sessions. There are well documented advantages of supplementation of nutrients after resistance and endurance training, but not with repeated sprints.
  • a program for enhancing muscle adaptation resulting from repeated sprints training comprising providing nutrition and guidance on training to an athlete to improve the muscle protein synthesis, the program comprising:
  • composition comprising protein or essential amino acids and carbohydrates
  • -providing guidelines for consumption comprising a recommendation of the amount of the composition to consume not more than 30 minutes before exercising or more than 30 minutes after recovery from exercising based on a training regimen of the athlete, and
  • the invention relates to a nutritional kit comprising a plurality of compositions comprising protein or essential amino acids and carbohydrates and guidelines recommending that an athlete consume the composition within a certain time period before exercising and within a certain time period during recovery after repeated running of sprints.
  • the invention also relates to a use of a composition comprising protein or essential amino acids and carbohydrates for improving muscle protein synthesis wherein the use is in connection with repeated sprint exercise.
  • repeated sprint type training is anaerobic in nature, and involves nearly purely carbohydrate metabolism with a large breakdown in muscle glycogen. Accordingly, nutritional recommendations are for at least 1 to 1.5g of carbohydrate per kg body mass (a total of ⁇ 50 to 75g carbohydrate) to be consumed in the first several hours after this type of exercise training.
  • Figure 1 shows in myofibrillar protein synthetic rate resulted from repeated sprint exercise.
  • Figure 2 shows plasma essential amino acid (EAA, panel A) , branched-chain amino acid (BCAA, panel B) and total amino acid (panel C) concentration at rest and following repeated sprint cycling repetitions after prior ingestion of placebo or nutrient beverage 30 min before exercise.
  • EAA plasma essential amino acid
  • BCAA branched-chain amino acid
  • panel C total amino acid
  • nutrient provision increases anabolic signalling and myofibrillar protein synthesis after repeated sprint exercise
  • composition comprises carbohydrates and protein or essential amino acids in a carbohydrate to protein ratio in the range from 1:1 to 3:1, preferably in a ratio of 2:1.
  • the recommendation would be 1 to 1.5g CHO/kg.
  • the preferred composition comprises a total protein dose of 10 to 50 g protein, preferably 20 to 30 grams. In the use according to the invention this is the preferred amount.
  • the protein or amino acid constitute about 20% to about 40% by weight of the solids in the final product. In another embodiment, the protein or amino acid comprises about 30% by weight of the product.
  • the composition can be made so that there is a consistent and countable quantity of protein per single dose, for example, between about 2 grams to about 4 grams per dose.
  • the composition comprises a protein or essential amino acid content of about 2 grams to about 2.5 grams.
  • the composition may be in the form of a solid product, a gel, a liquid, or a ready to mix powder.
  • the protein-based product can also contain a discrete amount of fat in one or more products to provide any suitable amount of energy to an athlete.
  • each of the products can provide a fat amount up to 9g/300 cal.
  • the products can provide llg/360cal.
  • Each of the products can also provide a saturated fat amount up to 4g/300 cal or more.
  • the percentage of energy (e.g. in the form of calories) coming from fat can be up to about 25%.
  • the protein-based product comprises an amount of fat ranging from about 10% to about 40% by weight of the protein-based product.
  • the protein-based product comprises an amount of fat of about 30% by weight of the protein-based product.
  • the protein-based product can comprise a protein blend comprising soy protein isolates, whey protein isolates and calcium caseinate.
  • a protein blend comprising soy protein isolates, whey protein isolates and calcium caseinate.
  • An example of the protein blend is the Tri-sourceTM protein blend .
  • any suitable dietary protein may be such as, for example, animal proteins (e.g. milk proteins, meat proteins and egg proteins); vegetable proteins (e.g. soy protein, wheat protein, rice protein, and pea protein) ; mixtures of free amino acids; or combinations thereof. Milk proteins, such as casein and whey milk proteins, and soy proteins are particularly preferred.
  • the proteins may be intact or hydrolysed or a mixture of intact and hydrolysed proteins. It may be desirable to supply partially hydrolysed proteins (degree of hydrolysis between 2 and 20%), for example, for athletes believed to be at risk of developing cows' milk allergy. Generally, at least partially hydrolysed proteins are easier and faster to metabolize by the body. This is in particular true for amino acids.
  • the protein-based product contains single/essential amino acids such as, for example, leucine, valine and/or isoleucine.
  • the essential amino acids comprising added Leucine.
  • Leucine is an essential amino acid (EAA) , found as part of the family of branched chain amino acids (BCAA) . Ingestion of essential EAA stimulates the synthesis of skeletal muscle proteins with the branched-chain amino acids leucine, isoleucine, and valine suggested to play a critical role in this response.
  • EAA essential amino acid
  • BCAA branched chain amino acids
  • leucine has been investigated for its anabolic properties in many different tissues, including muscle. It is well established in cell culture and rat models that leucine increases the formation, and hence activation, of specific proteins that are involved in "turning on” protein synthesis.
  • the fat source has the advantage in providing for an improved mouth feel.
  • Any fat source is suitable.
  • animal or plant fats may be used.
  • n3-unsaturated and n6-unsaturated fatty acids may comprise the fat source.
  • the fat source may also contain long chain fatty acids and/or medium chain fatty acids.
  • milk fat, canola oil, almond butter, peanut butter, corn oil and/or high-oleic acid sunflower oil may be used.
  • Example 1 The repeated sprints exercise according to the invention are part of a sport, in either continual training for that sport, or in the competition itself.
  • Example 1 The repeated sprints exercise according to the invention are part of a sport, in either continual training for that sport, or in the competition itself.
  • Example 1 Example 1 :
  • the study employed a randomised, cross-over, double blind design incorporating diet and exercise manipulation. Subjects performed the same repeated sprint exercise protocol on two separate occasions with altered nutrient intervention (protein versus placebo) with each testing session separated by a two-week recovery period.
  • Time-motion analysis of several major team sport performances indicates maximal sprint activity occurs every ⁇ 50-100 s with sprint durations not exceeding 6 sec. Accordingly, in an effort to make the laboratory exercise simulation as "sports specific" as possible, subjects performed 10 x 6 s supra-maximal sprints beginning every 60 s at a load equivalent to 0.075 kp/kg body mass (BM) on an electronically-braked cycle ergometer.
  • BM body mass
  • Muscle biopsies were taken from the vastus lateralis (thigh) to measure activation (as assessed by changes in phosphorylation) of proteins involved in "turning on” protein synthesis (i.e. regulate mRNA translation) by standard Western blotting procedures. Muscle (i.e. myofibrillar) protein synthesis was also measured by a primed constant infusion of a stable isotope amino acid (i.e. [ring-13C6] phenylalanine) .
  • a stable isotope amino acid i.e. [ring-13C6] phenylalanine
  • Figure 1 shows myofibrillar (panel A) protein fractional synthetic rate (FSR) during recovery (15-240 min) from 10 ⁇ 6 s maximal effort repeated sprint cycling repetitions after prior ingestion of 500 mL placebo or nutrient beverage 30 min before exercise. Values are mean ⁇ SD.
  • Figure 2 shows plasma essential amino acid (EAA, panel A) , branched-chain amino acid (BCAA, panel B) and total amino acid (panel C) concentration at rest and following 10 ⁇ 6 s maximal effort repeated sprint cycling repetitions after prior ingestion of 500 mL placebo or nutrient beverage 30 min before exercise.
  • EAA protein fractional synthetic rate
  • Plasma EAA concentration was only significantly elevated above rest immediately post-exercise ( ⁇ 85%) with nutrient provision, an effect that was also evident following 60-90 min recovery ( ⁇ 50-60%) (P ⁇ 0.05; Figure 2A) .
  • the increase in EAA concentration with nutrient ingestion was higher than placebo immediately post- exercise and throughout the 30-90 min recovery period (P ⁇ 0.05) .
  • plasma BCAA concentration was increased above rest immediately post-exercise and remained elevated for 90 min during recovery with nutrient but not placebo treatment ( ⁇ 60-120%, P ⁇ 0.05; Figure 2B) .
  • the augmented post- exercise BCAA concentration with nutrient ingestion was also higher than placebo at the equivalent time-points (P ⁇ 0.05) .
  • FIG. 3 There were significant time ⁇ treatment interactions for p70 S6K thr389 phosphorylation (P ⁇ 0.05; Figure 4A) . Phosphorylation of p70 S6K significantly increased above rest with nutrient ingestion ( ⁇ 300%, P ⁇ 0.01) but not placebo ( ⁇ 95%) 15 min after cessation of exercise resulting in a significant treatment effect (P ⁇ 0.05) . Despite modest elevation in p70 S6K thr389 phosphorylation following 240 min recovery these changes were not significantly different from rest (40-70%; Figure 4A) .
  • Figure 1 Repeated sprint exercise resulted in myofibrillar protein synthetic rate that was greater with pre-exercise nutrient ingestion compared with placebo during the 15-240 min recovery period 0.083 ⁇ 0.023 vs. 0.056 ⁇ 0.031 % -h "1 , P ⁇ 0.05;
  • Figure 1 Repeated sprint exercise resulted in myofibrillar protein synthetic rate that was greater with pre-exercise nutrient ingestion compared with placebo during the 15-240 min recovery period 0.083 ⁇ 0.023 vs. 0.056 ⁇ 0.031 % -h "1 , P ⁇ 0.05;

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PCT/EP2010/068439 2009-11-29 2010-11-29 Method of enhancing muscle protein synthesis Ceased WO2011064373A1 (en)

Priority Applications (12)

Application Number Priority Date Filing Date Title
NZ600094A NZ600094A (en) 2009-11-29 2010-11-29 Method of enhancing muscle protein synthesis
CN201080053149.6A CN102665445B (zh) 2009-11-29 2010-11-29 提高肌肉蛋白质合成的方法
IN4085DEN2012 IN2012DN04085A (enExample) 2009-11-29 2010-11-29
JP2012540457A JP5810429B2 (ja) 2009-11-29 2010-11-29 筋タンパク質合成を強化する方法
HK13102989.4A HK1175664B (en) 2009-11-29 2010-11-29 Method of enhancing muscle protein synthesis
MX2012005646A MX2012005646A (es) 2009-11-29 2010-11-29 Metodo para mejorar la sintesis de proteinas del musculo.
RU2012127126/13A RU2503269C1 (ru) 2009-11-29 2010-11-29 Способ повышения синтеза мышечных протеинов
CA2781764A CA2781764A1 (en) 2009-11-29 2010-11-29 Method of enhancing muscle protein synthesis
PH1/2012/500875A PH12012500875A1 (en) 2009-11-29 2010-11-29 Method of enhancing muscle protein synthesis
AU2010323089A AU2010323089B2 (en) 2009-11-29 2010-11-29 Method of enhancing muscle protein synthesis
BR112012012811A BR112012012811A2 (pt) 2009-11-29 2010-11-29 metodo de intensificar a sintese de proteina no musculo
US13/511,854 US20130203645A1 (en) 2009-11-29 2010-11-29 Method of enhancing muscle protein synthesis

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EP09177423.2 2009-11-29
EP09177423.2A EP2327316B1 (en) 2009-11-29 2009-11-29 Method of enhancing muscle protein synthesis

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EP (1) EP2327316B1 (enExample)
JP (1) JP5810429B2 (enExample)
CN (1) CN102665445B (enExample)
AU (1) AU2010323089B2 (enExample)
BR (1) BR112012012811A2 (enExample)
CA (1) CA2781764A1 (enExample)
IN (1) IN2012DN04085A (enExample)
MX (1) MX2012005646A (enExample)
NZ (1) NZ600094A (enExample)
PH (1) PH12012500875A1 (enExample)
RU (1) RU2503269C1 (enExample)
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EP3634155A4 (en) 2017-05-12 2021-02-17 Axiom Foods Inc. RICE PRODUCTS AND SYSTEMS AND PROCESSES FOR THEIR PRODUCTION
BR112020002419A2 (pt) 2017-08-14 2020-07-28 Axcella Health Inc. aminoácido para o tratamento de doença do fígado
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