METHOD TO REDUCE MUSCLE ATROPHY FOLLOWING ORTHOPEDIC SURGERY

Abstract

A method for reducing muscle atrophy in an individual undergoing orthopedic surgery, the method comprising administering to said individual a mixture of protein and non-protein nutrients for 4-7 days pre-surgery and for 10-21 days post-surgery. The protein dosage is 15-30 g, of which 17-25% is leucine, 23-35% is 1-glutamine, 10-15% is 1-arginine and 1-2% is cysteine. The protein nutrients are derived from a combination of commercially available proteins and the appropriate free amino acid. The non-protein nutrients are a mono or disaccharide in the amount of 15-30%, N-acetyl-cysteine in the amount of 1-15% and the antioxidant Vitamin C.

Claims

1. A method for reducing muscle atrophy in an individual undergoing orthopedic surgery in which the operative limb undergoes any degree of muscle disuse post-surgery, the method comprising the step of administering to the individual a composition of proteins, amino acids, and non-protein nutrients 4-7 days pre surgery and 10-21 days post-surgery for simultaneously and synergistically activating multiple anabolic pathways and multiple anti-catabolic pathways in the operative limb to increase protein synthesis while inhibiting protein degradation.

2. The method of claim 1, wherein said amino acids include leucine, glutamine, arginine, and cysteine, and wherein said non-protein nutrients include a mono saccharide or a disaccharide, and N-acetyl cysteine.

3. The method of claim 1, wherein said amino acids include leucine in the amount of 2.5 to 7.5 grams, glutamine in the amount of 3.5 to 10.5 grams, arginine in the amount of 1.5 to 4.5 grams, and cysteine in the amount of 0.15 to 0.45 grams, and wherein said non-protein nutrients include a mono saccharide or a disaccharide, and N-acetyl cysteine.

4. The method of claim 1, wherein the composition of protein, amino acid and non-protein nutrients optimally activates the mTOR, insulin-dependent and glutathione pathways and inhibits the formation of ROS.

5. The method of claim 1, wherein the schedule for administering the dose of protein, amino acid and non-protein nutrients is 1-3 times per day.

6. The method of claim 1, wherein the dosage unit of the protein nutrients is 15-30 grams.

7. The method of claim 1, wherein the amino acid composition contains 17-25% 1-leucine by weight based on the total dry weight of the protein nutrients.

8. The method of claim 7, wherein the composition of leucine will optimally activate the mTOR pathway.

9. The method of claim 7, wherein the amount 1-leucine is derived from a combination of proteins including whey, pea, casein, lactalbumin, rice, soy, and egg, and free leucine.

10. The method of claim 1, wherein the amino acid composition contains 23-35% glutamine by weight based on the total dry weight of the protein nutrients.

11. The method of claim 10, wherein the glutamine composition will restore glutathione levels and optimally activate the mTOR pathway.

12. The method of claim 10, wherein the amount 1-glutamine is derived from a combination of proteins including whey, pea, casein, lactalbumin, rice, soy and egg, and free glutamine.

13. The method of claim 1, wherein the amino acid contains 10-15% 1-arginine by weight based on the total dry weight of the protein nutrients.

14. The method of claim 13, wherein the arginine composition will optimally activate the mTOR pathway.

15. The method of claim 13, wherein the amount of 1-arginine is derived from a combination of proteins including whey, pea, casein, lactalbumin, rice, soy and egg, and free arginine.

16. The method of claim 1, wherein the amino acid composition of the protein nutrients contains 1-2% 1-cysteine by weight based on the total dry weight of the protein nutrients.

17. The method of claim 16, wherein the amount 1-cysteine is derived from a combination of proteins including whey, pea, casein, lactalbumin, rice, soy and egg.

18. The method of claim 1, wherein the non-protein nutrient is a monosaccharide or disaccharide in the amount of 15-30% by weight based on the total dry weight of the composition.

19. The method of claim 18, wherein the monosaccharide or disaccharide activates insulin dependent pathways.

20. The method of claim 1, wherein the non-protein nutrient is N-acetyl cysteine in the amount of 3-15% by weight based on the total dry weight of the composition.

21. The method of claim 1, wherein vitamin C is present in 100-500% of the RDA.

22. The method of claim 1, wherein the method decreases the pain index in a patient within 4 weeks after surgery.

23. The method of claim 1, wherein the method increases physical function within 4 weeks after surgery.

24. The method of claim 1, wherein the method increases total plasma protein levels within 4 weeks after surgery.

25. The method of claim 1, wherein the method increases the blood amino acid level of leucine by at least 10% within 2 weeks after surgery.

26. The method of claim 1, wherein the method increases the blood amino acid level of glutamine by at least 10% within 2 weeks after surgery.

27. The method of claim 1, wherein the method increases the blood amino acid level of arginine by at least 10% within 2 weeks after surgery.

28. The method of claim 1, wherein the method increases the levels of the active form of glutathione by at least 10% in the body, within 2 weeks after surgery.

29. The method of claim 1, wherein the method decreases reactive oxygen species by at least 10% in the body, within 2 weeks after surgery.

30. The method of claim 1, wherein the form of the composition is a pharmaceutical composition, a food product or a dietary supplement.

31. The method of claim 1, wherein the composition is in the form of a dry powder that is reconstituted with water, juice or skim milk.

32. The method of claim 1, wherein the composition is in the form of a ready to drink beverage, in the form of a bar, or in the form of a gel.

33. The method of claim 1, wherein the composition has a total caloric composition of 90-250 calories.

34. The method of claim 1, wherein the composition has a total weight of 20 to 50 grams.

35. A method for reducing muscle atrophy in an individual who requires partial immobilization due to injury, the method comprising the step of administering to the individual a composition of proteins, amino acids, and non-protein nutrients 10-21 days post-injury for simultaneously and synergistically activating multiple anabolic and multiple anti-catabolic pathways in the injured limb to increase protein synthesis while inhibiting protein degradation.

36. The method of claim 35, wherein said amino acids include leucine, glutamine, arginine, and cysteine, and wherein said non-protein nutrients include a monosaccharide or a disaccharide, and N-acetyl cysteine.

37. The method of claim 35, wherein said amino acids include leucine in the amount of 2.5 to 7.5 grams, glutamine in the amount of 3.5 to 10.5 grams, arginine in the amount of 1.5 to 4.5 grams, and cysteine in the amount of 0.15 to 0.45 grams, and wherein said nutrients are a monosaccharide or a disaccharide, and N-acetyl cysteine.

38. The method of claim 35, wherein the composition of protein, amino acid and non-protein nutrients optimally activates the mTOR, insulin-dependent and glutathione pathways and inhibits the formation of ROS.

39. The method of claim 35, wherein the dosage schedule for administering the dose of protein nutrients is 1-3 times per day.

40. The method of claim 35, wherein the amino acid composition contains 17-25% 1-leucine by weight based on the total dry weight of the protein nutrients.

41. The method of claim 40, wherein the amount of 1-leucine is derived from a combination of proteins including whey, pea, casein, lactalbumin, rice, soy and egg, and free leucine.

42. The method of claim 35, wherein the amino acid composition s contains 23-35% 1-glutamine by weight based on the total dry weight of the protein nutrients.

43. The method of claim 42, wherein the amount of 1-glutamine is derived from a combination of proteins including whey, pea, casein, lactalbumin, rice, soy and egg and free glutamine.

44. The method of claim 35, wherein the amino acid composition contains 10-15% 1-arginine by weight based on the total dry weight of the protein nutrients.

45. The method of claim 44, wherein the amount 1-arginine is derived from a combination of proteins including whey, pea, casein, lactalbumin, rice, soy and egg, and free arginine.

46. The method of claim 36, wherein the amino acid composition contains 1-2% 1-cysteine by weight based on the total dry weight of the protein nutrients.

47. The method of claim 46, wherein the amount 1-cysteine can be derived from any combination of proteins including whey, pea, casein, lactalbumin, rice, soy and egg.

48. The method of claim 36, wherein the nutrients include a monosaccharide or disaccharide in the amount of 10-20% by weight based on the total dry weight of the composition.

49. The method of claim 36, wherein the nutrient is N-acetyl cysteine is in the amount of 1-15% by weight based on the total dry weight of the composition.

50. The method of claim 36, wherein vitamin C is present in 100-500% of the RDA.

51. The method of claim 36, wherein the form of the composition is a pharmaceutical composition, a food product or a dietary supplement.

52. The method of claim 36, wherein the composition is in the form of a dry powder that is reconstituted with water, juice or skim milk.

53. The method of claim 36, wherein the composition is in the form of a ready to drink beverage, in the form of a bar, or in the form of a gel.

54. The method of claim 36, wherein the composition has a total caloric composition of 90-250 calories.

55. The method of claim 36, wherein the composition has a total weight of 20-50 grams.

56. A method for reducing disuse atrophy in an individual who is confined to a bed for an extended period or who has age related sarcopenia, the method comprising the step of administering to the individual a composition of proteins, amino acids, and non protein nutrients to simultaneously and synergistically activate multiple anabolic pathways to increase muscle protein synthesis and multiple anti-catabolic pathways to inhibit protein degradation.

57. The method of claim 56, wherein said amino acids include leucine, glutamine, arginine, and cysteine, and wherein said non-protein nutrients include a monosaccharide or a disaccharide, and N-acetyl cysteine.

58. The method of claim 56, wherein said amino acids include leucine in the amount of 2.5 to 7.5 grams, glutamine in the amount of 3.5 to 10.5 grams, arginine in the amount of 1.5 to 4.5 grams, and cysteine in the amount of 0.15 to 0.45 grams, and wherein said nutrients are a monosaccharide or a disaccharide, and N-acetyl cysteine.

59. The method of claim 56, wherein the composition of protein, amino acid and non-protein nutrients optimally activates the mTOR, insulin-dependent and glutathione pathways and inhibits the formation of ROS.

60. The method of claim 56, wherein the dosage schedule for administering the dose of protein, amino acids and non-protein nutrients is 1-3 times per day.

61. The method of claim 56, wherein the amino acid composition contains 17-25% 1-leucine by weight based on the total dry weight of the protein nutrients.

62. The method of claim 61, wherein the amount of 1-leucine is derived from a combination of proteins including whey, pea, casein, lactalbumin, rice, soy and egg and free leucine.

63. The method of claim 56, wherein the amino acid composition s contains 23-35% 1-glutamine by weight based on the total dry weight of the protein nutrients.

64. The method of claim 63, wherein the amount of 1-glutamine is derived from a combination of proteins including whey, pea, casein, lactalbumin, rice, soy and egg and free glutamine.

65. The method of claim 59, wherein the amino acid composition contains 10-15% 1-arginine by weight based on the total dry weight of the protein nutrients.

66. The method of claim 65, wherein the amount 1-arginine is derived from a combination of proteins including whey, pea, casein, lactalbumin, rice, soy and egg and free arginine.

67. The method of claim 56, wherein the amino acid composition contains 1-2% 1-cysteine by weight based on the total dry weight of the protein nutrients.

68. The method of claim 67, wherein the amount 1-cysteine can be derived from any combination of proteins including whey, pea, casein, lactalbumin, rice, soy and egg

69. The method of claim 56, wherein the nutrients include a monosaccharide or disaccharide in the amount of 10-20% by weight based on the total dry weight of the composition.

70. The method of claim 56, wherein the nutrient is N-acetyl cysteine is in the amount of 1-15% by weight based on the total dry weight of the composition.

71. The method of claim 56, wherein vitamin C is present in 100-500% of the RDA.

72. The method of claim 56, wherein the form of the composition is a pharmaceutical composition, a food product or a dietary supplement.

73. The method of claim 56, wherein the composition is in the form of a dry powder that is reconstituted with water, juice or skim milk.

74. The method of claim 56, wherein the composition is in the form of a ready to drink beverage, in the form of a bar, or in the form of a gel.

75. The method of claim 56, wherein the composition has a total caloric composition of 90-250 calories.

76. The method of claim 56, wherein the composition has a total weight of 20-50 grams.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0048] FIG. 1 is a diagram showing the multiple biochemical mechanism pre and post-surgery responsible for the increased degree of muscle atrophy following orthopedic surgery.

[0049] FIG. 2 is chart showing the rate of muscle atrophy in different disease and surgical conditions.

[0050] FIG. 3 is a diagram showing how the inventive method decreases muscle atrophy by simultaneously activating multiple biochemical mechanisms to increase protein synthesis and decrease protein degradation before and after surgery.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

[0051] The inventive method uses a multi-pronged nutritional approach to synergistically stimulate multiple pathways that increase protein synthesis and inhibit multiple pathways that increase protein degradation.

[0052] An unexpected result of the invention is that its use of specific nutrients that have multiple effects on protein synthesis. Glutamine not only stimulates mTOR signaling, but also plays a critical role in restoring glutathione levels, thereby inhibiting protein degradation. Arginine also stimulates mTOR signaling and increases amino acid delivery to muscle cells to facilitate protein synthesis.

[0053] Similarly, the addition of high glycemic sugars in the form of mono saccharides and/or disaccharides stimulate insulin, a powerful hormone that activates protein synthesis via mTOR signaling, increases protein synthesis independently via an amino acid transport mechanism and also serves as a strong inhibitor of protein degradation.

[0054] Another unexpected result of the invention is that consumption of the inventive composition prior to surgery increases muscle protein levels and, at the same time, primes the cells' anabolic machinery since under normal surgical procedure patients do not consume nutrition the night before or the day of surgery. Anabolic priming delays the initiation of surgery-induced muscle atrophy.

[0055] Another unexpected result of the invention is that it raises antioxidant levels prior to surgery. One of the major causes of arthritis, the primary reason for knee and hip replacements, is elevated levels of ROS. Increased levels of ROS inhibit mTOR and increase protein degradation. Thus even before surgery the biochemical environment of the operative limb is predisposed toward muscle atrophy.

[0056] The preferred embodiment of the inventive method consists of protein, the amino acids leucine, glutamine, arginine and cysteine, a mono or disaccharide, N-acetyl cysteine, vitamin C, a sweetener and coloring in a dry powder that can be mixed with water, juice or skim milk.

[0057] Whole protein has been shown to increase protein synthesis by raising blood amino acid levels.

[0058] Leucine is an essential amino acid that plays a pivotal role in activating mTOR, the major signaling pathway for protein synthesis. In the preferred embodiment, leucine can be derived from any commercially available protein including whey, pea, casein, rice, soy and egg or consist of the free amino acid.

[0059] Glutamine is considered a conditionally essential amino acid. Glutamine is the amino acid found in the largest concentration in the muscle. Glutamine has multiple roles in stimulating protein synthesis and inhibiting protein degradation. Glutamine activates mTOR by controlling leucine transport into the muscle. Glutamine is also one of the amino acids comprising glutathione, the body's master antioxidant. Glutathione, by neutralizing reactive oxygen species, prevents protein degradation since ROS are an important signal for activating protein degradation. In the preferred embodiment, glutamine can be derived from any commercially available protein. In the preferred embodiment, leucine can be derived from any commercially available protein including whey, pea, casein, rice, soy and egg or consist of the free amino acid.

[0060] The amino acid cysteine is also one of the three amino acids, along with glycine and glutamine that comprises glutathione. Cysteine consumption is the rate-limiting step for glutathione synthesis. In the preferred embodiment, cysteine can be derived from cysteine-enriched proteins such as lactalbumin or egg protein.

[0061] Arginine is an amino acid that independently activates the mTOR signaling pathway and also plays an important role in increasing the transport of key nutrients, such as amino acids, into the muscle cells. In the preferred embodiment, arginine can be derived from any commercially available protein including whey, pea, casein, rice soy and egg or consist of the free amino acid.

[0062] N-acetyl cysteine is a sulphur-containing compound that contains cysteine, a critical substrate for the synthesis of glutathione.

[0063] Vitamin C is an antioxidant that can be used safely with patients undergoing a surgical procedure. By reducing ROS, vitamin C neutralizes a key element involved in activating protein degradation. Unlike the antioxidant Vitamin E, Vitamin C is not contraindicated prior to surgery.

[0064] FIG. 3 shows how the inventive methods works by simultaneously activating multiple mechanisms to increase protein synthesis and decrease protein degradation pre and post-surgery.

[0065] FIG. 3How the Inventive Method Works

[0066] The preferred embodiment of the inventive method contains a high glycemic sugar in the form of a mono or disaccharide such as glucose, glucose polymers, dextrose, maltose, maltodextrin, sucrose, high fructose corn syrup, beet sugar, or cane sugar. High glycemic sugars are more effective in stimulating insulin, a critical hormone that is responsible for activating protein synthesis thru multiple pathways and for inhibiting protein degradation.

[0067] The preferred embodiment includes a flavor component for imparting a characteristic taste and a sweetener to improve palatability.

[0068] The range of intact protein ranges from 15 to 30 grams per serving. The intact protein can be selected from a combination of commercially available proteins including whey, pea, casein, lactalbumin, rice and soy.

[0069] The inventive method requires a specific amount of the amino acids leucine, arginine, glutamine and cysteine as shown in the table below. Since all intact proteins contain these amino acids in varying amounts, the combination of proteins selected determines the amount of free amino acids that must be added to the inventive composition to achieve the required levels. The free amino acids added will vary based on the different types of intact protein used in the inventive composition. As an example Table 1 below shows the different levels per gram of arginine, glutamine and leucine, in six different commercially available proteins.

TABLE-US-00001 TABLE 1 Whey enriched with Whey Pea Casein Lactalbumin Soy Egg Arginine 0.02 0.09 0.03 0.03 0.08 0.05 Glutamine 0.14 0.17 0.18 0.13 0.19 0.12 Leucine 0.09 0.08 0.08 0.08 0.08 0.07

[0070] Table 2 below illustrates the range of leucine, glutamine, arginine and cysteine as a percentage of total protein at three different levels, 15, 20 and 30 grams of protein. The range of leucine is 17% to 25% of total protein. The range of glutamine is 23% to 35% of total protein. The range of arginine is 10% to 15% of total protein. The range of cysteine is 1 to 2% of total protein.

TABLE-US-00002 TABLE 2 LOW PREFERRED HIGH PROTEIN PROTEIN PROTEIN LEVEL LEVEL LEVEL (15 grams) (20 grams) (30 grams) % % % Grams Protein Grams Protein Grams Protein Leucine 2.5 17% 5 25% 7.5 25% Glutamine 3.5 23% 7 35% 10.5 35% Arginine 1.5 10% 3 15% 4.5 15% Cysteine 0.15 1% 0.3 2% 0.45 2%

Example of Preferred Embodiment

[0071]

TABLE-US-00003 % Dry Ingredient g Weight Whey Protein 9.0 26% Whey enriched with lactalbumin 7.0 20% Pea Protein 4.0 12% Free Leucine 3.0 9% Free Glutamine 4.0 12% Free Arginine 2.0 6% Cane Sugar 4.0 12% N-acetyl cysteine 0.5 1% Vitamin C 0.2 1% Sweetener 0.1 0% Flavor 0.8 2% 34.6 100%

Example of Second Embodiment

[0072]

TABLE-US-00004 % Dry Ingredient g Weight Casein 4.0 16% Whey Protein 3.0 12% Whey enriched with lactalbumin 5.0 20% Pea Protein 3.0 12% Free Leucine 1.5 6% Free Glutamine 1.3 5% Free Arginine 1.0 4% Cane sugar 4.0 16% N-acetyl cysteine 0.5 2% Vitamin C 0.2 1% Flavor 0.8 3% Sweetener 0.1 0% TOTAL 24.4 100%

Example of Third Embodiment

[0073]

TABLE-US-00005 % Dry Ingredient g Weight Casein 5.0 10% Whey Protein 10.0 20% Whey enriched with lactalbumin 10.0 20% Pea Protein 5.0 10% Free Leucine 5.0 10% Free Glutamine 6.2 12% Free Arginine 3.2 6% Cane sugar 4.0 8% N-acetyl cysteine 0.5 1% Vitamin C 0.2 0% Flavor 0.8 2% Sweetener 0.1 0% TOTAL 50.0 100%

Example of Fourth Embodiment

[0074]

TABLE-US-00006 % Dry g Weight Whey Protein 8 23% Pea Protein 4 11% Soy Protein 4 11% Egg Protein 4 11% Free Leucine 3.4 10% Free Glutamine 4.1 12% Free Arginine 2.1 6% Cane Sugar 4 11% N-acetyl cysteine 0.5 1% Vitamin C 0.2 1% Flavor 0.8 2% Sweetener 0.1 0% TOTAL 35.2 100%

Example of Fifth Embodiment

[0075]

TABLE-US-00007 % Dry g Weight Casein 4.0 11% Whey Protein 5.0 13% Pea Protein 4.0 11% Soy Protein 3.0 8% Egg Protein 4.0 11% Cane sugar 6.0 16% N-acetyl cysteine 1.0 3% Free Glutamine 3.9 10% Free Leucine 3.3 9% Free Arginine 2.0 5% Vitamin C 0.2 1% Flavor 0.8 2% Sweetener 0.1 0% TOTAL 37.3 100%

[0076] Administration of the inventive method to a group of total knee replacement patients four to seven days prior to surgery and 10 to 14 days post-surgery would produce the following results when compared to a similar group that did not receive the inventive method:

[0077] 1. A 20-40% drop in muscle atrophy within 14 days after surgery.

[0078] 2. An increase in total plasma amino acid levels within 14 days after surgery, thereby ensuring that protein synthesis continues at optimum levels.

[0079] 3. An increase in plasma leucine within 14 days after surgery, thereby ensuring that protein synthesis continues at optimum levels.

[0080] 4. An increase in plasma glutamine levels within 14 days after surgery, thereby increasing glutathione levels.

[0081] 5. A decrease in ROS within 14 days after surgery thereby decreasing protein degradation.

[0082] 6. An increase in muscle strength within 14 days after surgery.

[0083] 7. A decrease in pain parameters within 21 days after surgery.

[0084] 8. An increase in normal function within 21 days after surgery.

ADVANTAGES OF THE PRESENT INVENTION

[0085] An advantage of the present invention is to reduce the rate of muscle atrophy that occurs in the 10-21 day period following orthopedic surgery by 20-40%.

[0086] Another advantage of the present invention is to increase muscle protein synthesis in the 4-7 period prior to surgery.

[0087] Another advantage of the present invention is to increase total amino acid levels in the blood in the 10-21 day period following orthopedic surgery.

[0088] Another advantage of the present invention is to reduce protein degradation in the 10-21 day period following orthopedic surgery.

[0089] Another advantage of the present invention is to reduce the time necessary for full return of muscle strength and function in the 10-21 day period following orthopedic surgery.

[0090] Another advantage of the present invention is to provide a cost-effective palatable method that encourages patient compliance.

[0091] Another advantage of the present invention is to increase plasma levels of leucine, an important amino acid involved in activating protein synthesis.

[0092] Another advantage of the present invention is to reduce oxidative stress that is a normal consequence of surgical trauma.

[0093] Another advantage of the present invention is to reduce the pain index of patients for four weeks following surgery.

[0094] Another advantage of the present invention is to increase insulin, a hormone involved in activating protein synthesis as well as inhibiting protein degradation.

[0095] Another advantage of the present invention is to reduce muscle atrophy in an individual who requires partial immobilization due to injury.

[0096] Another advantage of the present invention is to simultaneously and synergistically activate multiple anabolic and multiple anti-catabolic pathway in an individual who requires partial immobilization due to injury

[0097] A latitude of modification, change and substitution is intended in the foregoing disclosure, and in some instances, some features of the invention will be employed without a corresponding use of other features. Accordingly, it is appropriate that the appended claims be construed broadly and in a manner consistent with the spirit and scope of the invention herein.

REFERENCES

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