Login| Sign Up| Help| Contact|

Patent Searching and Data


Title:
SPORTS AND NUTRITIONAL SUPPLEMENT FORMULATIONS
Document Type and Number:
WIPO Patent Application WO/2020/231906
Kind Code:
A1
Abstract:
A nutritional composition, the consumption of which provides a method for enhancing lean muscle stimulus, growth, strength and recovery, creating and prolonging muscle pumps, supporting endurance, strength, performance, size and stamina, providing a transducer effect for nitric oxide, increasing nutrient delivery and/or promoting increased vascular response in individuals.

Inventors:
AMYX LINDY (US)
HOSPELHORN GABE (US)
CHOUDHURY SAMBHU (US)
Application Number:
PCT/US2020/032314
Publication Date:
November 19, 2020
Filing Date:
May 11, 2020
Export Citation:
Click for automatic bibliography generation   Help
Assignee:
BGS HOLDINGS LLC (US)
International Classes:
A23L33/00; A61K35/20; A61K35/64
Domestic Patent References:
WO2014083438A22014-06-05
Foreign References:
US20180263944A12018-09-20
US20080255101A12008-10-16
Other References:
SONG ET AL.: "Tea Is the Major Source of Flavan-3-ol and Flavonol in the U.S. Diet", 2008, XP055761729, Retrieved from the Internet [retrieved on 20200722]
WEBMD: "L-CITRULLINE", 26 February 2019 (2019-02-26), XP055761752, Retrieved from the Internet [retrieved on 20200721]
"L-Citrulline vs L-Citrulline DL-Malate: A Helpful Guide", NOOTROPICSOURCE, 6 March 2019 (2019-03-06), Retrieved from the Internet [retrieved on 20200721]
"Glutathione", 19 February 2019 (2019-02-19), XP055761746, Retrieved from the Internet [retrieved on 20200721]
MEDICINENET: "Ornithine", 8 June 2017 (2017-06-08), XP055761751, Retrieved from the Internet [retrieved on 20200721]
Attorney, Agent or Firm:
JENEI, Stephen R. (US)
Download PDF:
Claims:
CLAIMS

What is claimed is:

1. A composition for acutely raising nitric oxide levels in a subject, comprising: an

effective amount of L-citrulline, an effective amount of glutathione, an effective amount of ornithine; an effective amount of citicoline; and an effective amount of a source of nitric oxide; wherein the composition acutely raises nitric oxide levels in a subject above a level provided by the available sources of nitric oxide in the subject prior to administration of the composition.

2. The composition of claim 1, wherein the L-citrulline in the composition comprises 5- 8g-

3. The composition of claim 2, wherein the L-citrulline in the composition ranges from about 1 wt % to about 80 wt %.

4. The composition of claim 3, wherein the L-citrulline in the composition is provided as L-citrulline DL-malate.

5. The composition of claim 4, wherein the L-citrulline and DL-malate are present in the composition at a weight percent concentration ratio of about 2: 1, respectively.

6. The composition of claim 1, wherein the glutathione in the composition is present as reduced glutathione

7. The composition of claim 6, wherein the glutathione comprises from about 1 wt % to about 80 wt % of the composition.

8. The composition of claim 7, wherein the glutathione in the composition comprises 400 to 700 mg.

9. The composition of claim 1, wherein the ornithine in the composition is present as L- orni thine HC1.

10. The composition of claim 9, wherein the ornithine comprises from about 1 wt % to about 80 wt % of the composition.

11. The composition of claim 10, wherein the ornithine in the composition comprises 0.7- 0.9 g.

12. The composition of claim 1, wherein the source of nitric oxide is selected from the group consisting of beet root extract, vitamin Bl, collard green extract, nut powders, spinach extract, broccoli extract, lettuce extract, celery, kale, watercress, carrot, arugula, mustard greens, or a combination thereof.

13. The composition of claim 12, wherein the source of nitric oxide is beet root extract.

14. The composition of claim 13, wherein the source of nitric oxide in the composition a comprises 300-700 mg.

15. The composition of claim 1, wherein the citicoline in the composition comprises 350- 600 mg.

16. The composition of claim 15, wherein the composition further comprises at least one flavan-3-ol compound selected from the group consisting of monomers, oligomers, polymers, glycosides and pharmaceutically acceptable salts of the following: (+)- catechin, (-)-epicatechin, epigallocatechin, epicatechin gallate, epigallocatechin gallate, epiafzelechin, and fisetinidol.

17. The composition of claim 16, wherein the at least one flavan-3-ol compound is

provided as a green tea extract.

18. The composition of claim 17, wherein the green tea extract comprises at least 25% epigallocatechin gallate (EGCG) or more.

19. The composition of claim 18, wherein the at least one flavan-3-ol compound

comprises 300-700 mg.

20. The composition of claim 1, wherein the composition further comprises vitamin C.

21. The composition of claim 20, wherein the vitamin C comprises 200-3000 mg.

22. The composition of claim 1, wherein the citrulline is present in a 5: 1 to 15: 1 ratio with the glutathione.

23. The composition of claim 1, wherein the composition further comprises at least one anti-oxidant selected from the group consisting of idebenone, co-enzyme Q10, vitamin E, ALA (Alpha Lipoic Acid), vitamin C, carnosine, tocotrienols, flavonoids, ALC, vinpocetine, selenium, lycopene, creatine, arginine, taurine, cysteine, NADH, resveratrol, resveratrol-arginine conjugate (ResArgin), ginkgo biloba, oligomeric proanthocyanidins, and phenolic antioxidants and folic acid, folate, folinic acid and tetrahydrofolate.

24. The composition of claim 23, wherein the at least one anti-oxidant is lycopene.

25. The composition of claim 24, wherein the wherein lycopene comprises 20 to 80 mg.

26. A nutritional composition for improving nutrition in a subject, comprising: an

effective amount of citicoline, an effective amount of L-citrulline, and an effective amount of glutathione; wherein the composition promotes a healthy cardiovascular system and cognitive well-being.

27. The composition of claim 26, wherein the composition further comprises an ingredient that inhibits the breakdown of nitric oxide.

28. The composition of claim 27, wherein the ingredient that inhibits the breakdown of nitric oxide comprises an anti-oxidant selected from the group consisting of idebenone, co-enzyme Q10, vitamin E, ALA, vitamin C, carnosine, tocotrienols, flavonoids, ALC, vinpocetine, selenium, lycopene, creatine, arginine, taurine, cysteine, NADH, resveratrol, resveratrol-arginine conjugate (ResArgin), ginkgo biloba, oligomeric proanthocyanidins, and phenolic antioxidants and folic acid, folate, folinic acid and tetrahydrofolate.

29. The composition of claim 27, wherein the ingredient that inhibits the breakdown of nitric oxide is lycopene.

30. The composition of claim 29, wherein the lycopene comprises 20 to 80 mg.

31. The composition of claim 30, wherein the composition further comprises one or more components selected from the group consisting of a protein source, a lipid source, a carbohydrate source and combinations thereof.

32. The composition of claim 31, wherein the composition further comprises a carbohydrate source of the nutritional composition.

33. The composition of claim 32, wherein the carbohydrate source can comprise a component selected from the group consisting of maltodextrin, corn starch, modified starch, sucrose and combinations thereof.

34. The composition of claim 26, wherein the nutritional composition is in the form selected from the group consisting of a soluble powder, a liquid concentrate, a ready- to-drink formulation and combinations thereof.

35. A method of acutely raising nitric oxide levels in a subject, comprising: administering to the subject a therapeutically effective amount of a composition as recited in any of claims 1-34.

36. A method of treating a subject for a condition or disorder that is responsive to nitric oxide therapy, comprising: administering nutritional supplements comprising an effective amount of L-citrulline, an effective amount of glutathione, an effective amount of ornithine; an effective amount of citicoline; and an effective amount of a source of nitric oxide; wherein the compositions are useful in achieving and maintaining desired nitric oxide levels in subjects.

37. The method of claim 36, wherein the nitric oxide related pathology comprises a

member selected from the group consisting of Alzheimer's disease, angina, asthma, congestive disorders, Crohn's disease, deep vein thrombosis, dementia, diabetes (types, 1, 2 and 3), diabetic foot disorders, diminished exercise capacity, endothelial dysfunction, endotoxemia, erectile dysfunction, fibromyalgia, heart attack, heart failure, hypertension, inflammatory bowel disease, leaky gut, macular degeneration, monocyte-mediated arterial plaque formation, motor dysfunction, multiple sclerosis, obesity, oxidation of LDL, periodontal disease, peripheral arterial disease, platelet stickiness, portal hypertension, pregnancy/pre-eclampsia, premature ejaculation, pulmonary hypertension, Raynaud's disease, renal failure, sleep apnea, smooth muscle cell proliferation, stroke, and vasculitis.

38. The method of claim 37, wherein the treating of the subject is prophylactic.

39. The method of claim 38, wherein acutely raising nitric oxide levels in the subject comprises raising salivary nitrite levels in the subject beyond a level of the salivary nitrite in the subject as compared to a level prior to administering the therapeutically effective combination.

Description:
SPORTS AND NUTRITIONAL SUPPLEMENT FORMULATIONS

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of priority under 35 U.S.C. §119(e) to U.S. Provisional Application Serial No. 62/846,358, entitled“SPORTS AND NUTRITIONAL

SUPPLEMENT FORMULATIONS”, filed May 10, 2019, and to U.S. Provisional

Application Serial No. 62/877,974, entitled“SPORTS AND NUTRITIONAL

SUPPLEMENT FORMULATIONS”, filed July 24, 2019, the contents of which are hereby incorporated by reference in their entirety for any purpose.

BACKGROUND OF THE INVENTION

1. Field of the Invention

[0001] The field of art disclosed herein pertains generally relates to a device and method to dispense small droplets of liquid, and more particularly to measuring the volume of dispensed droplets.

2. Description of the Related Art

[0002] Sports and athletic participation is a complex process of preparation, action and recovery. Every element of participation and success in an athletic event involves use of energy that defines an efficiency in gaining an advantage over a competitor.

[0003] An ability to have more energy to deliver active pre-event practice, more ability to sustain and perform during the event and increased ability to recover from an event can mean the difference in a competitive environment of a positive or negative result.

[0004] Labeled“sports drinks” have enhanced participation with caffeine, sugar and electrolytes although the results of these preparations have resulted in higher energy but resulted in increased agitation, post-high lows, hydration (without additional benefits) respectively. Some higher dosage caffeine preparations have been implicated in some child addictions and even deaths.

[0005] Nitric Oxide (NO) is a free radical, actively produced in the human body. NO plays a role in the normal functioning of the cardiovascular, nervous, pulmonary, gastrointestinal, renal, and immune systems. Nitric oxide precursors have been known at elevated levels in addition to the diet of the individual to enhance exercise performance. L-arginine, citrulline and glutathione by enhancing endothelial NO production can provide for greater aerobic capacity and improved exercise performance. Use of additional elements that are nonpharmaceutical products can“naturally” allow for enhanced sports related function and can be modified in use and dosage for different sports activities and recoveries.

[0006] Aerobic exercise capacity is partly limited by vascular transport of oxygen and nutrients to end organs such as the heart and skeletal muscles. Vascular transport is, in turn, partly regulated by the elaboration of endothelial-derived nitric oxide (EDNO). Administration of physiologically acceptable compounds which enhance the elaboration of endogenous nitric oxide by the host allow for greater vascular transport and enhanced aerobic performance. Alternatively, compounds, or combinations of compounds, may be administered to enhance nitric oxide production. The production of nitric oxide contributes significantly to blood flow regulation and aerobic capacity during exercise.

[0007] There are a significant number of cardiovascular disorders, where the individuals' ambulatory abilities are extensively impaired. These include individuals who suffer severe fatigue with exercise, which condition frequently is associated with heart failure or chronic obstructive pulmonary disease. These disorders can include atherosclerosis affecting the coronary or limb arteries which can be manifested by angina (chest pain) or intermittent claudication (leg pain) with walking. Enhancing aerobic capacity to enhance performance would be of great advantage to these patients.

[0008] In the high-performance athlete, the ability to increase oxygen carrying capacity and aerobic capacity is an advantage in ultimate performance. Similar abilities are enhanced with long term training in a high altitude which allows for higher blood volume of cells with hemoglobin allowing for better results in activities that require high cardiovascular actions.

[0009] The use of L-arginine for prophylaxis and therapy in the case of atherosclerosis is shown in U.S. Patent No. 5,428,070. Physical capacity of individuals involved in muscular exertion is improved by administration of high levels of basic amino acids in addition to the diet normal for the individual. The basic amino acids are administered prior to the anticipated muscular exertion, particularly in association with substances which are antioxidants or other substances which enhance vascular nitric oxide synthesis or activity to cause vasodilation of vessels supplying exercising skeletal muscles and thereby enhance aerobic capacity as noted in U.S. Patent No. 6, 117,872. BRIEF SUMMARY

[0010] The present disclosure relates to compositions and methods for acutely raising nitric oxide levels in a subject. The acute raising of nitric oxide levels can be beneficial to the health of a subject.

[0011] Some embodiments of the present disclosure include a composition comprising ingredients that increase blood flow for energy, for improving an individual's endurance, and for enhancing body/muscle recovery in athletes.

[0012] The present disclosure relates to a composition, which in some embodiments is a dietary supplement that may be useful for increasing blood flow for energy, endurance, and after-workout body/muscle recovery and, in certain embodiments, for uses related to human sports performance. Also described in some embodiments is the method for using the composition, such as for increasing blood flow for energy, endurance, and after-workout body/muscle recovery and, in certain embodiments, for uses related to human sports performance. Some embodiments include kits, comprising the composition to be consumed according to a dietary regimen for increasing blood flow for energy, endurance, and after- workout body/muscle recovery in humans.

[0013] Athletic Formulation

[0014] Some embodiments of the present disclosure promote a healthy cardiovascular system, prolonged endurance, and enhanced performance. Some embodiments of the present disclosure can be consumed daily for its preventive health benefits or as needed before or after intense physical activity.

[0015] In one or more embodiments, the synergistic composition comprises at least the active ingredients citrulline, glutathione and ornithine in varying concentrations. Some embodiments of the present disclosure can be used by athletes to increase endurance, decrease inflammation, and enhance recovery. Some embodiments of the present disclosure can be used as a healthier option for increasing energy and as a natural option for health improvement.

[0016] In one or more embodiments, the synergistic composition comprises at least the active ingredients citrulline (an a-amino acid), glutathione (GSH), and ornithine (a non- proteinogenic amino acid) in varying concentrations.

[0017] In one or more embodiments, the synergistic composition comprises at least the active ingredients citrulline, glutathione (GSH), ornithine, and one or more additional active ingredients selected from the group consisting of a source of nitric oxide and citicoline (also known as CDP-choline or cytidine 5'-diphosphocholine), in varying concentrations. [0018] In another embodiment, the synergistic composition comprises at least the active ingredients citrulline, glutathione, ornithine, a source of nitric oxide and citicoline, in varying concentrations.

[0019] In one or more embodiments, the synergistic composition can include a source of nitric oxide selected from the group consisting of beet root extract, vitamin Bl, collard green extract, nut powders, spinach extract, broccoli extract, lettuce extract, celery, kale, watercress, carrot, arugula, mustard greens, or a combination thereof.

[0020] In one or more embodiments, the present invention comprises novel nutritional supplements comprising citrulline, glutathione and ornithine, wherein said compositions are useful in achieving and maintaining desired nitric oxide levels in subjects, and wherein said compositions may also be useful in restoring functional nitric oxide levels in nitric oxide- deficient subjects. The compositions may also lower blood pressure, and/or restore nitric oxide mediated cardiovascular benefits, including but not limited to aspects such as restoring endothelium function (i.e., flow mediated dilation).

[0021] In one or more embodiments, the disclosed compositions comprise embodiments wherein citrulline is present in 2-10 g, 4-8g, 5-8 g, or 6 g. In one or more embodiments, the disclosed compositions comprise embodiments wherein citrulline is present as L-citrulline DL- malate 2: 1, which combines two parts L-citrulline with one part DL-malic acid, wherein citrulline is present in 2-10 g, 4-8g, 5-8 g, or 6 g.

[0022] In one or more embodiments, the disclosed compositions comprise embodiments wherein glutathione is present in 300-900 mg, 400-800 mg, 500-700 mg, 550-650 mg, or 600 mg. In one or more embodiments, the disclosed compositions comprise embodiments wherein glutathione is present as reduced glutathione and is present in 100 to 900 mg; 150 to 850 mg; 200 to 800 mg; 250 to 800 mg; 300 to 700 mg; 400 to 700 mg; 450 to 650 mg; 500 to 600 mg; or 600 mg.

[0023] In one or more embodiments, the disclosed compositions comprise embodiments wherein ornithine is present in 0.2-10 g, 0.3-8g, 0.4-2 g, 0.5-1 g, 0.7-0.9 g or 0.8 g. In one or more embodiments, the disclosed compositions comprise embodiments wherein ornithine is present as L-orni thine HC1.

[0024] In one or more embodiments, the disclosed compositions comprise embodiments wherein a source of nitric oxide is present in 100-1000 mg, 200-800 mg, 300-700 mg, 350-600 mg, 350-500 mg, or 400 mg.

[0025] In one or more embodiments, the disclosed compositions comprise embodiments wherein the source of nitric oxide is beet root extract. In one or more embodiments, the disclosed compositions comprise embodiments wherein beet root extract is present in 100- lOOOmg, 200-800 mg, 300-700 mg, 350-500 mg, or 400 mg.

[0026] In one or more embodiments, the disclosed compositions comprise embodiments wherein citicoline is present in 200-800 mg, 350-600 mg, 450-550 mg or 500 mg.

[0027] In one or more embodiments, the disclosed compositions comprise embodiments wherein at least one flavan-3-ol compound is present. In one or more embodiments, the at least one flavan-3-ol compound is selected from the group consisting of monomers, oligomers, polymers, glycosides and pharmaceutically acceptable salts of the following: (+)-catechin, (-)- epicatechin, epigallocatechin, epicatechin gallate, epigallocatechin gallate, epiafzelechin, and fisetinidol. In one or more embodiments, the disclosed compositions comprise embodiments wherein at least one flavan-3-ol compound is present in 200-800 mg, 300-700 mg, 400-600 mg, 500-600 mg or 500 mg.

[0028] In one or more embodiments, the disclosed compositions comprise embodiments wherein green tea extract is present in 200-800 mg, 300-700 mg, 400-600 mg, 500-600 mg or 500 mg; and wherein the green tea extract comprises at least 10%, 15%, 20%, 25%, 30%, 35%, 40% epigallocatechin gallate (EGCG), or more.

[0029] In one or more embodiments, the disclosed compositions comprise embodiments wherein vitamin C is present in 200-3000 mg, 400-2000 mg, 500-1000 mg or 500-800 mg of vitamin C.

[0030] In one or more embodiments, the disclosed compositions comprise embodiments wherein the citrulline is present in a 1 :5 to 20: 1 ratio, 2.5: 1 to 15: 1 ratio, 5: 1 to 15: 1 ratio, 8: 1 to about 12: 1 ratio, 9: 1 to about 11 : 1 ratio or 10: 1 ratio with the glutathione.

[0031] Extreme Athletic Formulation

[0032] Some embodiments of the present disclosure promote a healthy cardiovascular system, prolonged endurance, and enhanced performance during extreme athletic activity. Some embodiments of the present disclosure can be consumed daily for its preventive health benefits or as needed before or after intense physical activity.

[0033] In one or more embodiments, the synergistic composition comprises at least the active ingredients citrulline, glutathione and ornithine in varying concentrations. In one or more embodiments, the synergistic composition comprises at least the active ingredients citrulline, glutathione, ornithine and lycopene in varying concentrations.

[0034] In one or more embodiments, the synergistic composition comprises at least the active ingredients citrulline, glutathione, ornithine, and one or more additional active ingredients selected from the group consisting of a source of nitric oxide, citicoline, a flavan- 3-ol compound, and an anti-oxidant in varying concentrations. In one or more embodiments, the synergistic composition further comprises one or more vitamins.

[0035] In another embodiment, the synergistic composition comprises at least the active ingredients citrulline, glutathione, ornithine, a source of nitric oxide, citicoline, a flavan-3-ol compound, and an anti-oxidant in varying concentrations, in varying concentrations.

[0036] In another embodiment, the synergistic composition comprises at least the active ingredients N-acetylcysteine amide, beta-alanine, catechins, a choline, citrulline, glutathione, L-ornithine, D-ribose, and Rhodiola rosea extract in varying concentrations, in varying concentrations.

[0037] In another embodiment, the synergistic composition comprises at least the active ingredients N-acetylcysteine amide, beta-alanine, catechins, citicoline, citrulline, glutathione, L-ornithine, D-ribose, and Rhodiola rosea extract in varying concentrations, in varying concentrations.

[0038] In another embodiment, the synergistic composition comprises at least the active ingredients N-acetylcysteine amide, beta-alanine, green tea extract, citicoline, citrulline, glutathione, L-omithine, D-ribose, and Rhodiola rosea extract in varying concentrations, in varying concentrations.

[0039] In another embodiment, the synergistic composition comprises at least the active ingredients N-acetylcysteine amide, beta-alanine, a cyanidin, green tea extract (EGCG), citicoline, citrulline, glutathione, L-ornithine, D-ribose, and Rhodiola rosea extract in varying concentrations, in varying concentrations.

[0040] In another embodiment, the synergistic composition comprises at least the active ingredients N-acetylcysteine amide, beta-alanine, cyanidin-3-glucoside (Cy-g) or cyanidin-3,5- diglucoside (Cy-dg), green tea extract (EGCG), citicoline, citrulline, glutathione, L-ornithine, D-ribose, and Rhodiola rosea extract in varying concentrations, in varying concentrations.

[0041] In another embodiment, the synergistic composition comprises at least the active ingredients N-acetylcysteine amide, beta-alanine, cyanidin-3-glucoside (Cy-g) or cyanidin-3,5- diglucoside (Cy-dg), green tea extract (EGCG), citicoline, citrulline, glutathione, L-ornithine, D-ribose, Rhodiola rosea extract, and L-theanine in varying concentrations, in varying concentrations.

[0042] In one or more embodiments, the synergistic composition can include a source of nitric oxide selected from the group consisting of beet root extract, vitamin Bl, collard green extract, nut powders, spinach extract, broccoli extract, lettuce extract, celery, kale, watercress, carrot, arugula, mustard greens, or a combination thereof. [0043] In one or more embodiments, the disclosed synergistic compositions comprise embodiments wherein citrulline is present in 2-10 g, 4-9g, 5-9 g, 6-8 g, or 8 g. In one or more embodiments, the disclosed compositions comprise embodiments wherein citrulline is present as L-citrulline DL-malate 2: 1, which combines two parts L-citrulline with one part DL-malic acid, wherein citrulline is present in 2-10 g, 4-9g, 5-9 g, 6-8 g, or 8 g.

[0044] In one or more embodiments, the disclosed compositions comprise embodiments wherein glutathione is present in 300-1200 mg, 400-1000 mg, 500-900 mg, 600-800 mg, or 800 mg. In one or more embodiments, the disclosed compositions comprise embodiments wherein glutathione is present as reduced glutathione and is present in 100 to 1500 mg; 150 to 1200 mg; 200 to 1100 mg; 250 to 1000 mg; 300 to 950 mg; 400 to 900 mg; 450 to 850 mg; 500 to 800 mg; or 800 mg.

[0045] In one or more embodiments, the disclosed compositions comprise embodiments wherein ornithine is present in 0.1-12 g, 0.2-10 g, 0.3-8g, 0.4-2 g, 0.5-1 g, 0.7-0.9 g or 0.8 g. In one or more embodiments, the disclosed compositions comprise embodiments wherein ornithine is present as L-orni thine HC1.

[0046] In one or more embodiments, the disclosed compositions comprise embodiments wherein a source of nitric oxide is present in 100-1000 mg, 200-800 mg, 300-700 mg, 350-600 mg, 350-500 mg, or 400 mg.

[0047] In one or more embodiments, the disclosed compositions comprise embodiments wherein the source of nitric oxide is beet root extract. In one or more embodiments, the disclosed compositions comprise embodiments wherein beet root extract is present in 100- lOOOmg, 200-800 mg, 300-700 mg, 350-500 mg, or 400 mg.

[0048] In one or more embodiments, the disclosed compositions comprise embodiments wherein citicoline is present in 200-800 mg, 350-600 mg, 450-550 mg or 500 mg.

[0049] In one or more embodiments, the disclosed compositions comprise embodiments wherein at least one flavan-3-ol compound is present. In one or more embodiments, the at least one flavan-3-ol compound is selected from the group consisting of monomers, oligomers, polymers, glycosides and pharmaceutically acceptable salts of the following: (+)-catechin, (-)- epicatechin, epigallocatechin, epicatechin gallate, epigallocatechin gallate, epiafzelechin, and fisetinidol. In one or more embodiments, the disclosed compositions comprise embodiments wherein at least one flavan-3-ol compound is present in 200-800 mg, 300-700 mg, 400-600 mg, 500-600 mg or 500 mg.

[0050] In one or more embodiments, the disclosed compositions comprise embodiments wherein green tea extract is present in 200-800 mg, 300-700 mg, 400-600 mg, 500-600 mg or 500 mg; and wherein the green tea extract comprises at least 10%, 15%, 20%, 25%, 30%, 35%, 40% epigallocatechin gallate (EGCG), or more.

[0051] In one or more embodiments, the disclosed compositions comprise embodiments wherein at least one anti-oxidant is present. In one or more embodiments, the at least one anti oxidant is selected from the group consisting of idebenone, co-enzyme Q10, vitamin E, ALA (Alpha Lipoic Acid), vitamin C, carnosine, tocotrienols, flavonoids, ALC, vinpocetine, selenium, lycopene, creatine, arginine, taurine, cysteine, NADH, resveratrol, resveratrol- arginine conjugate (ResArgin), ginkgo biloba, oligomeric proanthocyanidins, and phenolic antioxidants and folic acid, folate, folinic acid and tetrahydrofolate.

[0052] In one or more embodiments, the at least one anti-oxidant is lycopene. In one or more embodiments, the disclosed compositions comprise embodiments wherein lycopene is present in a range selected from: 5 to 90 mg; 10 to 85 mg; 15 to 80 mg; 20 to 80 mg; 20 to 70 mg; or 20 to 40 mg.

[0053] In one or more embodiments, the disclosed compositions comprise embodiments wherein at least one vitamin, mineral or nutritional supplement is present. In one or more embodiments, the at least one vitamin, mineral or nutritional supplement is selected from the group consisting of vitamin B complex, folic acid, niacin, niacinamide, pantothenic acid, pyridoxine HCL, vitamin B2, folate, biotin, vitamin C, vitamin D, vitamin D3, vitamin E, vitamin K, cyanocobalamin, inositol, thiamine, thiamine mononitrate, calcium pantothenate, mixed tocopherols, d-alpha tocopheryl acetate, magnesium, calcium, calcium carbonate, calcium chelate, calcium di-phosphate, calcium phosphate, iron, magnesium carbonate, magnesium citrate, magnesium oxide, magnesium phosphate, manganese chelate, manganese sulfate, potassium, potassium chelate, potassium chloride, sodium, zinc, vanadyl sulphate, chromium, chromium chloride, chromium picolinate, and chromium polynicotinate.

[0054] In this regard, suitable concentrations for a number of anti-oxidant agents in the various embodiments of the present invention are as follows: Vitamin E (d-alpha-tocopheryl acetate): 40 to 4000 I.U, with a usual range of 200 to 1200 I.U., and typically 200 to 600 I.U. Vitamin C (ascorbic acid or a salt thereof): 100 to 3000 mg, with a usual range of 200 to 1000 mg. Lycopene: 5 to 90 mg, with usual ranges of 10 to 80 mg, and 20 to 60 mg. Co-Enzyme Q10: 4 to 400 mg, with a usual range of 10 to 100 mg. Selenium: 10 to 250 pg, with a usual range of 20 to 50 pg. Zinc: 2.5 to 100 mg, with a usual range of 10 to 50 mg. Glutathione: 100 to 1000 mg, with a usual range of 400 to 600 mg. L-carnitine: 1 to 5 grams, with a usual range of 2 to 3 grams. Pentoxifylline: 200 to 1500 mg, with a usual range of 300 to 1200 mg. [0055] In one or more embodiments, the disclosed compositions comprise embodiments wherein vitamin C is present in 200-3000 mg, 400-2000 mg, 500-1000 mg or 500-800 mg of vitamin C.

[0056] In one or more embodiments, the disclosed compositions comprise embodiments wherein the citrulline is present in a 1 :5 to 20: 1 ratio, 2.5: 1 to 15: 1 ratio, 5: 1 to 15: 1 ratio, 8: 1 to about 12: 1 ratio, 9: 1 to about 11 : 1 ratio or 10: 1 ratio with the glutathione.

[0057] In one or more embodiments, the disclosed compositions may further comprise inositol-stabilized arginine silicate (also known as "arginine silicate," "arginine silicate inositol," and "ASI”). In one or more embodiments, the disclosed compositions comprise embodiments wherein inositol-stabilized arginine silicate is present in a therapeutically effective amount of about 2-5,000 mg, 250-2,500 mg, 500-2,000 mg or 500 mg-1,000 mg. In one or more embodiments, the disclosed compositions comprise embodiments wherein inositol-stabilized arginine silicate is administered in a therapeutically effective amount per kg body weight per day of about 1 mg/kg, 1.5mg/kg, 2.0 mg/kg, 2.5 mg/kg, 3 mg/kg, 4.0 mg/kg, 5.0 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 25 mg/kg, 30 mg/kg, 35 mg/kg, 40 mg/kg, 45 mg/kg 50 mg/kg, 55 mg/kg, 60 mg/kg, 65 mg/kg, 70 mg/kg, 75 mg/kg, 80 mg/kg, 85 mg/kg, 90 mg/kg, 95 mg/kg, 100 mg/kg, 125 mg/kg, 150 mg/kg, 200 mg/kg, 250 mg/kg, 300 mg/kg, 350 mg/kg, 400 mg/kg, 450 mg/kg, 500 mg/kg, 550 mg/kg, 600 mg/kg, 650 mg/kg, 700 mg/kg, 750 mg/kg, 800 mg/kg, 850 mg/kg, 900 mg/kg, 950 mg/kg, 1 g/kg, 5 g/kg, 10 g/kg, or more. A commercially available, bioavailable form of inositol- stabilized arginine silicate is available in purified form as Nitrosigine® from Nutrition 21 (Purchase, NY) and Glanbia Nutritionals, Inc. (Carlsbad, CA).

[0058] In one or more embodiments, the disclosed compositions may further comprise creatine or creatine derivatives. In one or more embodiments, the disclosed compositions comprise embodiments wherein creatine, a creatine derivative or mixtures thereof is present in a therapeutically effective amount of about 0.1-10 g, 0.5-5 g, 0.9-2.5 g or 1-1.5 g of creatine or creatine derivative. Creatine and creatine derivatives are widely available from a number of commercial sources. Commercially available creatine derivatives include creatine phosphate, creatine citrate, magnesium creatine, alkaline creatine, creatine pyruvate, creatine hydrates (including, but not limited to creatine monohydrate), and creatine malate. Glycocyamine, an in vivo precursor of creatine, is also commercially available and suitable in the practice of the present invention. The supplement preferably comprises creatine malate or creatine monohydrate. [0059] Muscle Metabolism Formulation

[0060] Some embodiments of the present disclosure provide for methods and compositions for improved muscle metabolism. Some embodiments of the present disclosure provide for methods and compositions for improved muscle recovery after exercise. Some embodiments of the present disclosure can be consumed daily for its preventive health benefits or as needed before or after intense physical activity.

[0061] In one or more embodiments, the synergistic composition for improved muscle metabolism and exercise recovery comprises at least the active ingredients ecdysterone or ecdysteroid-containing compounds and extracts, citrulline, glutathione and ornithine.

[0062] In another embodiment, the synergistic composition for improved muscle metabolism and exercise recovery comprises at least the active ingredients ecdysterone or ecdysteroid-containing compounds and extracts, citrulline, glutathione, ornithine and lycopene.

[0063] In another embodiment, the synergistic composition for improved muscle metabolism and exercise recovery comprises at least the active ingredients ecdysterone or ecdysteroid-containing compounds and extracts, citrulline, glutathione, ornithine, and one or more additional active ingredients selected from the group consisting of a source of nitric oxide, citicoline, a flavan-3-ol compound, and an anti-oxidant.

[0064] In another embodiment, the synergistic composition for improved muscle metabolism and exercise recovery comprises at least the active ingredients ecdysterone or ecdysteroid-containing compounds and extracts, citrulline, glutathione, ornithine, a source of nitric oxide, citicoline, a flavan-3-ol compound, and an anti-oxidant.

[0065] In one or more embodiments, the present invention provides for methods of administering to a mammal in need of treatment a composition comprising an ecdysteroid wherein the concentration of ecdysteroid is sufficient to increase growth hormone transcription in tissue. It is further contemplated that for the methods of treatment the administration of the composition includes all modes known in the art for delivering therapeutic compositions to a mammal. In one or more embodiment, the composition can be orally administered.

[0066] In one or more embodiments, the ecdysteroid is a phytoecdy steroid.

Phytoecdysteroids, sometimes called phytoecdysones, are plant-derived eedysteroids. In another embodiment, the phytoecdy steroid is synthesized by plants or an ecdysteroid synthesized by members of the phylum arthropoda or a synthetic version thereof. In another embodiment, the ecdysteroid is 20-hydroxyecdysone (20HE). In another embodiment, the ecdysteroid composition can be a plant extract. In one embodiment, the ecdysteroid composition can be an extract of spinach. In one or more embodiments, the phytoecdysones that are used can be obtained by extraction from plants and fungi. Some plants or fungi that produce phytoecdysteroids include Achyranthes bidentata, Tinospora cordifolia, Pfaffia paniculata, Leuzea carthamoides, Rhaponticum uniflorum, Serratula coronata, Cordyceps, spinach and asparagus. Ecdysones prepared by hemisynthesis can also be used. In one or more embodiments, the phytoecdysones are selected from 20-hydroxyecdysone, makisterone A, 24-epimakisterone A, 24(28)- dehydromakisterone A, 20,26-dihydroxyecdysone, and combinations of two or more of these components.

In one or more embodiments, the phytoecdysones can be in pure form or contained in a more or less enriched plant extract. Advantageously, the phytoecdysones implemented according to the invention are in the form of a plant extract enriched with phytoecdysones, with the extract containing at least 1% phytoecdysones by weight. In one or more embodiments, the extract contains between 1% and 50% phytoecdysones, between 1% and 20% phytoecdysones, between 1.5% and 10%, and greater than 2% phytoecdysones by weight.

[0067] In one or more embodiments, the phytoecdysones are orally administered at a rate of 0.25 to 10, 0.5 to 7.5, or 1 to 5 mg per kg of body weight per day. In another embodiment, the

[0068] In one or more embodiments, the ecdysteroid is present in a dosage of 10 to 5000 mg. In another embodiment, the ecdysteroid is present in a dosage of at least 10, 25, 50, 100, 250, 500, 750, 1000, 1250, 1500, or 2000 mg or more. In another embodiment, the ecdysteroid is present in a dosage of at most 500, 750, 1000, 1250, 1500, 2000, 2500, 3000, 3500, 4000, 4500, 5000 mg or less.

[0069] In some embodiments, the ecdysteroid comprises at a daily dose of about 1-5000 mg/day, preferably at about 30-1000 mg/day, more preferably about 50-1000 mg/day, and even more preferably about 100-900 mg/day or 200-800 mg/day. In some embodiments, the ecdysteroid comprises multiple daily doses of 10, 50, 100, 200, 300, 400, 500, 600, 700, 800 or more mg per dose.

[0070] In one or more embodiments, the synergistic composition comprises at least the active ingredients ecdysteroid or ecdysteroid extract, citrulline, glutathione and ornithine in varying concentrations. In one or more embodiments, the synergistic composition comprises at least the active ingredients ecdysteroid or ecdysteroid extract, citrulline, glutathione, ornithine and lycopene in varying concentrations.

[0071] In one or more embodiments, the synergistic composition comprises at least the active ingredients ecdysteroid or ecdysteroid extract, citrulline, glutathione, ornithine, and one or more additional active ingredients selected from the group consisting of a source of nitric oxide, citicoline, a flavan-3-ol compound, and an anti-oxidant in varying concentrations. In one or more embodiments, the synergistic composition further comprises one or more vitamins.

[0072] In another embodiment, the synergistic composition comprises at least the active ingredients ecdysteroid or ecdysteroid extract, citrulline, glutathione, ornithine, a source of nitric oxide, citicoline, a flavan-3-ol compound, and an anti-oxidant in varying concentrations, in varying concentrations.

[0073] In yet another aspect, a method for improving muscle mass and muscle strength in a mammal is provided, comprising administering to the mammal an effective amount of the composition described herein. The mammal is preferably a human, more preferably an athlete. In a further aspect of the disclosure, a method for promoting aerobic and anaerobic sport/physical performance in a mammal is provided, comprising administering to the mammal an effective amount of the composition disclosed herein. In yet another aspect, a method for treating conditions associated with or characterized by muscle atrophy in a mammal is provided, comprising administering to the mammal an effective amount of the composition described herein.

[0074] In one or more embodiments, the disclosed synergistic compositions comprise embodiments wherein citrulline is present in 2-10 g, 4-9g, 5-9 g, 6-8 g, or 8 g. In one or more embodiments, the disclosed compositions comprise embodiments wherein citrulline is present as L-citrulline DL-malate 2: 1, which combines two parts L-citrulline with one part DL-malic acid, wherein citrulline is present in 2-10 g, 4-9g, 5-9 g, 6-8 g, or 8 g.

[0075] In one or more embodiments, the disclosed compositions comprise embodiments wherein glutathione is present in 300-1200 mg, 400-1000 mg, 500-900 mg, 600-800 mg, or 800 mg. In one or more embodiments, the disclosed compositions comprise embodiments wherein glutathione is present as reduced glutathione and is present in 100 to 1500 mg; 150 to 1200 mg; 200 to 1100 mg; 250 to 1000 mg; 300 to 950 mg; 400 to 900 mg; 450 to 850 mg; 500 to 800 mg; or 800 mg.

[0076] In one or more embodiments, the disclosed compositions comprise embodiments wherein ornithine is present in 0.1-12 g, 0.2-10 g, 0.3-8g, 0.4-2 g, 0.5-1 g, 0.7-0.9 g or 0.8 g. In one or more embodiments, the disclosed compositions comprise embodiments wherein ornithine is present as L-orni thine HC1.

[0077] In one or more embodiments, the disclosed compositions comprise embodiments wherein a source of nitric oxide is present in 100-1000 mg, 200-800 mg, 300-700 mg, 350-600 mg, 350-500 mg, or 400 mg. [0078] In one or more embodiments, the disclosed compositions comprise embodiments wherein at least one flavan-3-ol compound is present. In one or more embodiments, the at least one flavan-3-ol compound is selected from the group consisting of monomers, oligomers, polymers, glycosides and pharmaceutically acceptable salts of the following: (+)-catechin, (-)- epicatechin, epigallocatechin, epicatechin gallate, epigallocatechin gallate, epiafzelechin, and fisetinidol. In one or more embodiments, the disclosed compositions comprise embodiments wherein at least one flavan-3-ol compound is present in 200-800 mg, 300-700 mg, 400-600 mg, 500-600 mg or 500 mg.

[0079] In one or more embodiments, the disclosed compositions comprise embodiments wherein green tea extract is present in 200-800 mg, 300-700 mg, 400-600 mg, 500-600 mg or 500 mg; and wherein the green tea extract comprises at least 10%, 15%, 20%, 25%, 30%, 35%, 40% epigallocatechin gallate (EGCG), or more.

[0080] In one or more embodiments, the disclosed compositions comprise embodiments wherein at least one anti-oxidant is present. In one or more embodiments, the at least one anti oxidant is selected from the group consisting of idebenone, co-enzyme Q10, vitamin E, ALA (Alpha Lipoic Acid), vitamin C, carnosine, tocotrienols, flavonoids, ALC, vinpocetine, selenium, lycopene, creatine, arginine, taurine, cysteine, NADH, resveratrol, resveratrol- arginine conjugate (ResArgin), ginkgo biloba, oligomeric proanthocyanidins, and phenolic antioxidants and folic acid, folate, folinic acid and tetrahydrofolate.

[0081] In one or more embodiments, the at least one anti-oxidant is lycopene. In one or more embodiments, the disclosed compositions comprise embodiments wherein lycopene is present in a range selected from: 5 to 90 mg; 10 to 85 mg; 15 to 80 mg; 20 to 80 mg; 20 to 70 mg; or 20 to 40 mg.

[0082] In one or more embodiments, the disclosed compositions comprise embodiments wherein at least one vitamin, mineral or nutritional supplement is present. In one or more embodiments, the at least one vitamin, mineral or nutritional supplement is selected from the group consisting of vitamin B complex, folic acid, niacin, niacinamide, pantothenic acid, pyridoxine HCL, vitamin B2, folate, biotin, vitamin C, vitamin D, vitamin D3, vitamin E, vitamin K, cyanocobalamin, inositol, thiamine, thiamine mononitrate, calcium pantothenate, mixed tocopherols, d-alpha tocopheryl acetate, magnesium, calcium, calcium carbonate, calcium chelate, calcium di-phosphate, calcium phosphate, iron, magnesium carbonate, magnesium citrate, magnesium oxide, magnesium phosphate, manganese chelate, manganese sulfate, potassium, potassium chelate, potassium chloride, sodium, zinc, vanadyl sulphate, chromium, chromium chloride, chromium picolinate, and chromium polynicotinate. [0083] Health and Medical Formulations

[0084] Some embodiments of the present disclosure promote a healthy cardiovascular system and can be consumed daily for its preventive health benefits or as needed. The invention further provides for compositions and methods for formulating compositions containing at least the active ingredients citicoline, citrulline, and glutathione, and methods for decreasing the likelihood of developing cardiovascular disease, decreasing triglyceride or LDL cholesterol levels, decreasing pain or inflammation, treating diabetes, chronic pulmonary diseases, or irritable bowel syndrome, decreasing symptoms of an autoimmune disease or allergic conditions.

[0085] The invention further provides for compositions and methods for formulating compositions containing at least the active ingredients citicoline, citrulline, and glutathione, and methods for reducing or treating a nitric oxide (NO) deficiency disorder in a nitric oxide- deficient subject, wherein said NO deficiency disorder is selected from the group consisting of: endothelial dysfunction, argininosuccinic aciduria, Huntington's disease, sickle cell disease, hyperhomocystinemia, acute chest syndrome, muscular dystrophy, dyslipidemia, pre eclampsia, and Alzheimer's disease.

[0086] In one or more embodiments, the synergistic composition comprises least the active ingredients citicoline, citrulline, and glutathione, and an ingredient that inhibits the breakdown of nitric oxide in varying concentrations, in varying concentrations.

[0087] In one or more embodiments, the ingredient that inhibits the breakdown of nitric oxide comprises an anti-oxidant selected from the group consisting of idebenone, co-enzyme Q10, vitamin E, ALA, vitamin C, carnosine, tocotrienols, flavonoids, ALC, vinpocetine, selenium, lycopene, creatine, arginine, taurine, cysteine, NADH, resveratrol, resveratrol- arginine conjugate (ResArgin), ginkgo biloba, oligomeric proanthocyanidins, and phenolic antioxidants and folic acid, folate, folinic acid and tetrahydrofolate.

[0088] In one or more embodiments, the present invention comprises novel nutritional supplements comprising citicoline, citrulline, and glutathione, and an ingredient that inhibits the breakdown of nitric oxide, wherein said compositions are useful in achieving and maintaining desired nitric oxide levels in subjects, and wherein said compositions may also be useful in restoring functional nitric oxide levels in nitric oxide-deficient subjects. The compositions may also lower blood pressure, and/or restore nitric oxide mediated cardiovascular benefits, including but not limited to aspects such as restoring endothelium function (i.e., flow mediated dilation). [0089] In one or more embodiments, the disclosed compositions comprise embodiments wherein citicoline is present in 100-1000 mg, 900 mg, 250-800 mg, 350-600 mg, 450-550 mg or 500 mg.

[0090] In one or more embodiments, the disclosed compositions comprise embodiments wherein citrulline is present in 1-10 g, 2-8 g, 3-7g, 4-6 g, or 5 g. In one or more embodiments, the disclosed compositions comprise embodiments wherein citrulline is present as L-citrulline DL-malate 2: 1, which combines two parts L-citrulline with one-part DL-malic acid, wherein citrulline is present in 1-10 g, 2-8 g, 3-7g, 4-6 g, or 5 g.

[0091] In one or more embodiments, the disclosed compositions comprise embodiments wherein glutathione is present in 300-800 mg, 350-700 mg, 400-650 mg, 450-550 mg, or 500 mg. In one or more embodiments, the disclosed compositions comprise embodiments wherein glutathione is present as reduced glutathione and is present in 100 to 900 mg; 150 to 850 mg; 200 to 800 mg; 250 to 800 mg; 300 to 700 mg; 350 to 650 mg; 400 to 600 mg; 450-550 mg; or 500 mg.

[0092] In one or more embodiments, the at least one ingredient that inhibits the breakdown of nitric oxide is lycopene. In one or more embodiments, the disclosed compositions comprise embodiments wherein lycopene is present in a range selected from: 5 to 90 mg; 10 to 85 mg; 15 to 80 mg; 20 to 80 mg; 20 to 70 mg; or 20 to 40 mg.

[0093] In one or more embodiments, the disclosed compositions comprise embodiments wherein at least one vitamin, mineral or nutritional supplement is present. In one or more embodiments, the at least one vitamin, mineral or nutritional supplement is selected from the group consisting of vitamin B complex, folic acid, niacin, niacinamide, pantothenic acid, pyridoxine HCL, vitamin B2, folate, biotin, vitamin C, vitamin D, vitamin D3, vitamin E, vitamin K, cyanocobalamin, inositol, thiamine, thiamine mononitrate, calcium pantothenate, mixed tocopherols, d-alpha tocopheryl acetate, magnesium, calcium, calcium carbonate, calcium chelate, calcium di-phosphate, calcium phosphate, iron, magnesium carbonate, magnesium citrate, magnesium oxide, magnesium phosphate, manganese chelate, manganese sulfate, potassium, potassium chelate, potassium chloride, sodium, zinc, vanadyl sulphate, chromium, chromium chloride, chromium picolinate, and chromium polynicotinate.

[0094] In this regard, suitable concentrations for a number of anti-oxidant agents in the various embodiments of the present invention are as follows: Vitamin E (d-alpha-tocopheryl acetate): 40 to 4000 I.U, with a usual range of 200 to 1200 I.U., and typically 200 to 600 I.U. Vitamin C (ascorbic acid or a salt thereof): 100 to 3000 mg, with a usual range of 200 to 1000 mg. Lycopene: 5 to 90 mg, with usual ranges of 10 to 80 mg, and 20 to 60 mg. Co-Enzyme Q10: 4 to 400 mg, with a usual range of 10 to 100 mg. Selenium: 10 to 250 mg, with a usual range of 20 to 50 mg. Zinc: 2.5 to 100 mg, with a usual range of 10 to 50 mg. Glutathione: 100 to 1000 mg, with a usual range of 400 to 600 mg. L-carnitine: 1 to 5 grams, with a usual range of 2 to 3 grams. Pentoxifylline: 200 to 1500 mg, with a usual range of 300 to 1200 mg.

[0095] In one or more embodiments, the disclosed compositions comprise embodiments wherein vitamin C is present in 200-3000 mg, 400-2000 mg, 500-1000 mg or 500-800 mg of vitamin C.

[0096] In one or more embodiments, the disclosed compositions comprise embodiments wherein the citrulline is present in a 1 :5 to 20: 1 ratio, 2.5: 1 to 15: 1 ratio, 5: 1 to 15: 1 ratio, 8: 1 to about 12: 1 ratio, 9: 1 to about 11 : 1 ratio or 10: 1 ratio with the glutathione.

[0097] In one or more embodiments, the nutritional composition comprises one or more components selected from the group consisting of a protein source, a lipid source, a carbohydrate source and combinations thereof.

[0098] In one or more embodiments, the protein source can comprise about 18% to about 28% of the energy of the nutritional composition. The protein source can include a protein hydrolysate. The protein source can comprise a component selected from the group consisting of casein hydrolysate, whey hydrolysate and combinations thereof. The protein hydrolysate can comprise cysteine.

[0099] In one or more embodiments, the protein source of the nutritional composition can comprise a portion as free amino acids. For example, the protein source can include approximately 80% to 85% of protein hydrolysate and approximately 15% to 20% of free amino acids.

[00100] In another embodiment, the lipid source comprises approximately 30% to about 45% of the energy of the nutritional composition. The lipid source can comprise a mixture of medium chain triglycerides and long chain triglycerides. The lipid source can comprise about 30% to about 80% by weight of medium chain triglycerides.

[00101] In another embodiment, the lipid source of the nutritional composition comprises a component selected from the group consisting of fractionated coconut oil, fish oil, sunflower oil, rapeseed oil, soy oil, milk fat, corn oil, soy lecithin and combinations thereof. In another embodiment, the nutritional composition contains omega-3 rich fatty acids.

[00102] In an embodiment, the nutritional composition comprises a lipid profile designed to have a polyunsaturated fatty acid omega-6 (n-6) to omega-3 (n-3) ratio of about 1 : 1 to about 10: 1. [00103] In an embodiment, the carbohydrate source of the nutritional composition provides about 30% to about 65% of the energy of the nutritional composition. The carbohydrate source can comprise a component selected from the group consisting of maltodextrin, corn starch, modified starch, sucrose and combinations thereof.

[00104] In an embodiment, the nutritional composition is free from lactose.

[00105] Exemplary Formulations

[00106] In an embodiment, the nutritional composition is in the form of a soluble powder, a liquid concentrate, a ready -to-drink formulation and combinations thereof.

[00107] The disclosed compositions may be in the form of powders, granules, suspensions, solutions in water or non-aqueous media, capsules, sachets, gums, tablets, dissolvable oral strips; and may further comprise thickeners, flavorings, diluents, emulsifiers, dispersing aids or binders.

[00108] In alternative embodiments, disclosed compositions (optionally referred to as supplements or nutritional supplements) may include carriers, thickeners, diluents, buffers, preservatives, surface active agents, flavorings and the like in addition to the key ingredients. The supplements may also include one or more active ingredients such as magnesium, potassium, calcium and the like. Certain embodiments further comprise calcium carbonate, microcrystalline cellulose, 15 coating (polyvinyl alcohol, macrogol, talc, titanium dioxide), stearic acid, croscarmellose sodium, magnesium stearate, or silica.

[00109] The supplements disclosed herein are preferably administered via oral routes. Compositions for oral administration include powders or granules, suspensions or solutions in water or non-aqueous media, capsules, sachets, gums, or tablets. Thickeners, flavorings, diluents, emulsifiers, dispersing aids or binders may also be incorporated. Also envisioned are oral strips that dissolve upon contact with saliva in the mouth.

[00110] In an embodiment, the novel compositions (also known as dietary supplements) as disclosed herein, comprise dietary nitrate, wherein said compositions are effective in modifying functional nitric oxide levels in a subject. Such compositions may be used to establish, restore and/or maintain desired nitric oxide levels.

[00111] The compositions described herein may further comprise vitamin C (ascorbic acid), thiamin (thiamin mononitrate), folate (folic acid), vitamin B12 (methylcobalamin) and potassium. In certain embodiments, the compositions comprise 1-2,000 mg vitamin C (ascorbic acid), 1-800 mg thiamin (thiamin mononitrate), 1-500 meg folate (folic acid), 1-500 meg vitamin B12 (methylcobalamin), and 1-500 mg potassium. In certain embodiments, vitamin C (ascorbic acid) comprises 110 mg, thiamin (thiamin mononitrate) comprises 90 mg, folate (folic acid) comprises 200 meg, vitamin B12 (methylcobalamin) comprises 200 meg, and potassium comprises 120 meg. Some embodiments further comprise absorbable dietary magnesium in about 1-400 mg per unit.

[00112] The compositions may further comprise calcium carbonate, microcrystalline cellulose, coating (polyvinyl alcohol, macrogol, talc, titanium dioxide), stearic acid, croscarmellose sodium, magnesium stearate, silica as well as thickeners, flavorings, diluents, emulsifiers, dispersing aids or binders. The compositions may be in the form of powders, granules, suspensions, solutions in water or non-aqueous media, capsules, sachets, gums, tablets, dissolvable oral strips.

DETAILED DESCRIPTION

[00113] For convenience, before further description of the present invention, certain terms employed in the specification, examples and appended claims are defined here.

[00114] The articles“a” and“an” are used herein to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article. By way of example,“an element” means one element or more than one element.

[00115] As used herein, the term "about" refers to plus or minus 10% of the referenced number. For example, a formulation comprising green tea extract at about 250 mg includes an amount of green tea extract between 225 and 275 mg. By“about” is meant a quantity, level, value, number, frequency, percentage, dimension, size, amount, weight or length that varies by as much as 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1% to a reference quantity, level, value, number, frequency, percentage, dimension, size, amount, weight or length.

[00116] “Administering” a composition can be effected or performed using any of the various methods and delivery systems known to those skilled in the art.

[00117] The term“bioavailability” includes, generally, the degree to which a drug or other substance becomes available to a subject following ingestion, administration, or exposure. In one embodiment, for example, the bioavailability of the quercetin compounds may be the bioavailability to a particular target tissue. For example, in an embodiment, the particular target tissue may require traversal of the stomach or the small intestines, therefore the bioavailability data may be obtained from this particular target tissue.

[00118] The terms "catechin", "epicatechin", "epigallocatechin", "epicatechin gallate", "epigallocatechin gallate", "epiafzelechin", "fisetinidol", "guibourtinidol", "mesquitol", and robinetinidol" refer to flavan-3-ol compounds and have their usual and ordinary meaning in the fields of organic chemistry and natural products, and include the various stereoisomers thereof. Where the C-2 and C-3 carbons define a trans configuration the molecule is a catechin. Where they define a cis configuration the molecule is an epicatechin

[00119] As used herein, chemical compounds or simply "compounds" may be identified either by their chemical structure, chemical name, or common name. In the event that the chemical structure, chemical name, or common name conflict, the chemical structure is determinative of the identity of the compound. The compounds described herein may contain one or more chiral centers and/or double bonds and therefore, may exist as stereoisomers, such as double-bond isomers (i.e., geometric isomers), enantiomers, or diastereomers. Accordingly, the chemical structures depicted herein encompass all possible enantiomers and stereoisomers of the illustrated or identified compounds including the stereoisomerically pure form (e.g., geometrically pure, enantiomerically pure, or diastereomerically pure) and enantiomeric and stereoisomeric mixtures. Enantiomeric and stereoisomeric mixtures can be resolved into their component enantiomers or stereoisomers using separation techniques or chiral synthesis techniques well known to the skilled artisan. The compounds may also exist in several tautomeric forms including the enol form, the keto form and mixtures thereof. Accordingly, the chemical structures encompass all possible tautomeric forms of the illustrated or identified compounds. The compounds described also encompass isotopically labeled compounds where one or more atoms have an atomic mass different from the atomic mass conventionally found in nature. Examples of isotopes that may be incorporated into the compounds of the invention include, but are not limited to, 2H, 3H, 13C, 14C, 15N, 180, 170 etc. Compounds may exist in unsolvated forms as well as solvated forms, including hydrated forms and as N-oxides. In general, compounds may be hydrated, solvated, or N-oxides. Certain compounds may exist in multiple crystalline or amorphous forms. Also contemplated are congeners, analogs, hydrolysis products, metabolites, and precursor or prodrugs of the compound. In general, all physical forms are equivalent for the uses contemplated herein and are intended to be within the scope of the present disclosure.

[00120] Disclosed are components to be used to prepare the disclosed compositions as well as the compositions themselves to be used within the methods and compositions disclosed herein. These and other materials are disclosed herein, and it is understood that when combinations, subsets, interactions, groups, etc. of these materials are disclosed that while specific reference of each various individual and collective combinations and permutation of these compounds may not be explicitly disclosed, each is specifically contemplated and described herein. For example, if a particular compound is disclosed and discussed and a number of modifications that can be made to a number of components including the compound are discussed, specifically contemplated is each and every combination and permutation of the components and the modifications that are possible unless specifically indicated to the contrary. Thus, if a class of components A, B, and C are disclosed as well as a class of components D, E, and F and an example of a combination component, A-D is disclosed, then even if each is not individually recited each is individually and collectively contemplated meaning combinations, A-E, A-F, B-D, B-E, B-F, C-D, C-E, and C-F are considered disclosed. Likewise, any subset or combination of these is also disclosed. Thus, for example, the sub group of A-E, B-F, and C-E would be considered disclosed. This concept applies to all aspects of this application including, but not limited to, steps in methods of making and using the disclosed compositions. Thus, if there are a variety of additional steps that can be performed it is understood that each of these additional steps can be performed with any specific embodiment or combination of embodiments of the disclosed methods.

[00121] Concentrations, amounts, and other numerical data may be expressed or presented herein in a range format. It is to be understood that such a range format is used merely for convenience and brevity and thus should be interpreted flexibly to include not only the numerical values explicitly recited as the limits or endpoints of the range, but also to include all the individual numerical values and/or sub-ranges encompassed within that range as if each numerical value (including fractions) and sub-range is explicitly recited. As an illustration, a numerical range of "about 1 to about 5" should be interpreted to include not only the explicitly recited values of about 1 to about 5, but also include individual values and sub-ranges within the indicated range. Thus, included in this numerical range are individual values such as 2, 2.6,

3, 3.8, and 4 and sub-ranges such as from 1-3, from 2-4, and from 3-5, etc., as well as 1, 2, 3,

4, and 5, individually.

[00122] As used herein a "concentrate" refers to an extract of a source that contains at least the same amount of active fractions, compounds, or other constituents, in a smaller volume than in the source itself. In one example, a "concentrate" may be a dried powder derived from a component that does not include the use of any solvents during the concentration process.

[00123] The term "dosage unit" is understood to mean a unitary, i.e. a single dose which is capable of being administered to a subject or patient, and that may be readily handled and packed, remaining as a physically and chemically stable unit dose comprising either the active ingredient as such or a mixture of it with solid or liquid pharmaceutical vehicle materials.

[00124] An "effective amount," "therapeutic amount," "therapeutic effective amount," or "effective dose" is an amount or dose sufficient to elicit a desired pharmacological or therapeutic effect in a mammalian subject; typically resulting in a measurable increase in nitric oxide production or availability. Therapeutic effectiveness may further be demonstrated by a decrease in the symptoms of the conditions being treated. An “effective amount” of a composition means an amount of the composition sufficient to cause the desired result in a given subject. The effective amount will vary from subject to subject and depending on the condition to be treated, the agent delivered, and the route of delivery. A person of ordinary skill in the art can perform routine titration experiments to determine such an amount. Depending upon the agent delivered, the effective amount of a composition can be delivered continuously, such as by a suppository, or at periodic intervals (for example, on one or more separate occasions). Desired time intervals of multiple amounts of a particular agent can be determined without undue experimentation by one skilled in the art. [00125] The term“food” includes all edible compositions regardless of form and thus includes gels, gel packs, liquids, syrups, and/or solids. A "food" or "food product" or "food composition" means a product or composition that is intended for ingestion by an animal, including a human, and provides nutrition to the animal.

[00126] As used herein, the term "green tea extract" covers an extract of Camellia sinensis , an evergreen tree belonging to the family Theaceae , or an extract from tea leaves treated with Bacillus subtilis spp. and then fermented, etc., regardless of the extraction method, extraction solvent, and the form of the extracted ingredient or of the extract. It also covers fractions obtained by fractionating the extracts with a specific solvent. The tea includes at least one selected from the group consisting of tea leaves, flowers, stems, fruits, roots, and the cores of stems and roots. The tea may preferably be tea leaves. In addition, the extract may preferably be in powder form. The extraction or fractionation may be performed using water, an organic solvent, or a mixed solvent thereof. The organic solvent may be an alcohol, isopropanol, acetone, hexane, ethyl acetate, carbon dioxide, or a mixed solvent of two or more of them, although not limited thereto. The number and method of the extraction or the fractionation is not particularly limited. For example, methods such as cold extraction, ultrasonic extraction, reflux cooling extraction, hot water extraction may be used. Preferably, the green tea extract of the present disclosure may be obtained by extracting or fractionating the active ingredient by cold or hot extraction, filtering the extract, and concentrating the filtrate under reduced pressure.

[00127] The term“increased performance” of a subject refers to an increase in the subject's mean peak power and/or an increase in the subject's mean average power over the course of several exercise intervals. Accordingly, a subject can experience“increased performance” even if the subject's peak power and/or mean power did not increase during any given exercise interval.

[00128] The term“percent by weight” of a theaflavin or theaflavins means the weight of such theaflavin or theaflavins as measured by high-performance liquid chromatography (HPLC), sometimes referred to as high-pressure liquid chromatography. While it is also possible to measure the percent by weight of theaflavins by using UV absorption techniques, such techniques detect ancillary materials and therefore report a higher and inaccurate percentage by weight of theaflavins than the HPLC method of measurement. Therefore, to provide the most accurate disclosure, all measurements and reporting of percentages by weight are done using HPLC. [00129] As used herein, the term“prevention” refers to any activity that reduces the burden of the individual later expressing disease symptoms. This can take place at primary, secondary and/or tertiary prevention levels, wherein: a) primary prevention avoids the development of symptoms/disorder/condition; b) secondary prevention activities are aimed at early stages of the condition/disorder/symptom treatment, thereby increasing opportunities for interventions to prevent progression of the condition/disorder/symptom and emergence of symptoms; and c) tertiary prevention reduces the negative impact of an already established condition/disorder/symptom by, for example, restoring function and/or reducing any condition/disorder/symptom or related complications.

[00130] The term“statistically significant” or“significantly” refers to statistical evidence that there is a difference. It is defined as the probability of making a decision to reject the null hypothesis when the null hypothesis is actually true. The decision is often made using the p- value.

[00131] A“subject” means any organism including, without limitation, a mammal such as a cat, a dog, a horse, a camel, and a primate (human or non-human). In the preferred embodiment, the subject is a human being.

[00132] As used herein, "synergistic" means more than the additive effect of the individual components against a mechanism of action. For example, if A1 produces response X, A2 produces response Y, then the combination of A1+A2>X+Y. In some situations F2 produces no response and the value for Y is equal to zero.

[00133] As used herein, the term“treatment” refers to an intervention made in response to a disease, disorder or physiological condition manifested by a subject, particularly a subject suffering from one or more of a disorder, disease or disease state. In some embodiments, the disorder, disease or disease state is a heart disease, diabetes, hypertension, allergic reactions, asthma, arthritis, cancer, prostate diseases, and oxidative stress. In some embodiments, the treatment refers to the improvement of health or performance, including the improvement of athletic performance, improved bone health, strengthened immune response, prevention of fatigue, reduction in recovery time following exercise, and for boosting energy. The aim of treatment may include, but is not limited to, one or more of the alleviation or prevention of symptoms, slowing or stopping the progression or worsening of a disease, disorder, or condition and the remission of the disease, disorder or condition. In some embodiments, “treatment” refers to both therapeutic treatment and prophylactic or preventative measures. Those in need of treatment include those already affected by a disease or disorder or undesired physiological condition as well as those in which the disease or disorder or undesired physiological condition is to be prevented. For example, in some embodiments, treatments reduce, alleviate, or eradicate the symptom(s) of the disease(s). In some embodiments, treatment can refer to enhancement of secondary effects of the disease, including enhancement or improvement of athletic performance.

[00134] The present disclosure relates to compositions and methods for acutely raising nitric oxide levels in a subject. The acute raising of nitric oxide levels can be beneficial to the health of a subject.

[00135] Some embodiments of the present disclosure include a composition comprising ingredients that increase blood flow for energy, for improving an individual's endurance, and for enhancing body/muscle recovery in athletes.

[00136] The present disclosure relates to a composition, which in some embodiments is a dietary supplement that may be useful for increasing blood flow for energy, endurance, and after-workout body/muscle recovery and, in certain embodiments, for uses related to human sports performance. Also described in some embodiments is the method for using the composition, such as for increasing blood flow for energy, endurance, and after-workout body/muscle recovery and, in certain embodiments, for uses related to human sports performance. Some embodiments include kits, comprising the composition to be consumed according to a dietary regimen for increasing blood flow for energy, endurance, and after- workout body/muscle recovery in humans.

[00137] Some embodiments of the present disclosure promote a healthy cardiovascular system, prolonged endurance, and enhanced performance.

[00138] Some embodiments of the present disclosure can be consumed daily for its preventive health benefits or as needed before or after intense physical activity.

[00139] Athletic Formulation

[00140] In some embodiments the synergistic composition is provided in the form of a powdered drink. In certain embodiments, the powdered composition comprises an effective amount of a combination of citrulline, glutathione and ornithine.

[00141] In some embodiments, the powder may further comprise additional active ingredients such as glutamine, glucosamine, branched chain amino acids, digestive enzymes, protein, collagen and sugar in various amounts.

[00142] In some embodiments the composition is provided in the form of a powdered drink where the powder may comprise additional inactive ingredients such as flavors, thickening agents, gelling agents, sweeteners, colorants, and preservatives. [00143] In certain embodiments, the synergistic combination of the active ingredients of citrulline, glutathione and ornithine, which provides increased blood flow when administered to human subjects, particularly vasodilation and antioxidant benefits. For example, the composition may have a positive effect on pre-exercise, recovery after strenuous exercise, vascular health, and connective tissue recovery. Combinations that add the additional ingredients may also have the same positive effects.

[00144] Certain embodiments of compositions have high concentrations of nitrates. In some instances, red spinach extract is a source of one of the highest concentrations of nitrates in nature. Nitrates are involved in vasodilation events throughout the human body. Some human clinical studies have shown reduction in blood pressure by the vasodilating mechanism of red beet extract, as well as its oxygenation of muscles during exercise, thus enhancing exercise tolerance. Thus, red beet extract improves and supports the cardiovascular, respiratory, and metabolic systems throughout the body.

[00145] In one or more embodiments, the synergistic composition comprises at least the active ingredients citrulline, glutathione and ornithine in varying concentrations. Some embodiments of the present disclosure can be used by athletes to increase endurance, decrease inflammation, and enhance recovery. Some embodiments of the present disclosure can be used as a healthier option for increasing energy and as a natural option for health improvement.

[00146] In one or more embodiments, the synergistic composition comprises at least the active ingredients citrulline (an a-amino acid), glutathione (GSH), and ornithine (a non- proteinogenic amino acid) in varying concentrations.

[00147] In one or more embodiments, the synergistic composition comprises at least the active ingredients citrulline, glutathione (GSH), ornithine, and one or more additional active ingredients selected from the group consisting of a source of nitric oxide and citicoline (also known as CDP-choline or cytidine S'-diphosphocholine), in varying concentrations.

[00148] In another embodiment, the synergistic composition comprises at least the active ingredients citrulline, glutathione, ornithine, a source of nitric oxide and citicoline, in varying concentrations.

[00149] In one or more embodiments, the synergistic composition can include a source of nitric oxide selected from the group consisting of beet root extract, vitamin Bl, collard green extract, nut powders, spinach extract, broccoli extract, lettuce extract, celery, kale, watercress, carrot, arugula, mustard greens, or a combination thereof.

[00150] In one or more embodiments, the methods and compositions discussed herein can include the use of a nitric oxide releasing compound (NORC). The NORCs can be any NORC suitable for administration to an animal. NORCs can be obtained from any suitable source, synthetic or natural. In various embodiments, the NORC comprises arginine. Sources of arginine include, without limitation, animal and plant proteins. Examples of plants considered rich in arginine content and suitable for use herein include, but are not limited to, legumes such as soy, lupins, and carob; grains such as wheat and rice; and fruits such as grapes. Seeds and nuts of plants such as cacao and peanut are also considered rich in arginine content and are therefore useful herein. Some examples of suitable animal proteins considered rich in arginine content are poultry and fish products. In certain embodiments, the NORC comprise one or more of L-Arg and nitric oxide-releasing derivatives thereof. The NORC can also be synthetically produced, according to any suitable means in the art. As with LCPUFA, the NORC content of any composition disclosed herein can include a blend of any natural or synthetic NORC. Both LCPUFA and NORC, whether natural or synthetic, can be obtained directly or provided by a commercial source.

[00151] In one or more embodiments, the methods and compositions discussed herein can include the use of compounds that enhance the production of nitric oxide. In one or more embodiments, the compounds that enhance the production of nitric oxide comprises a compound selected from the group consisting of L-arginine and policosanol.

[00152] In one or more embodiments, the methods and compositions discussed herein can include the use of compounds that inhibit the breakdown of nitric oxide. In one or more embodiments, the compounds that inhibit the breakdown of nitric oxide comprises an anti oxidant selected from the group consisting of idebenone, co-enzyme Q10, vitamin E, ALA, vitamin C, carnosine, tocotrienols, flavonoids, ALC, vinpocetine, selenium, lycopene, creatine, arginine, taurine, cysteine, NADH, resveratrol, resveratrol-arginine conjugate (ResArgin), ginkgo biloba, oligomeric proanthocyanidins, and phenolic antioxidants and folic acid, folate, folinic acid and tetrahydrofolate.

[00153] In another embodiment, the synergistic composition comprises from about 40 weight parts to about 1000 weight parts of a botanical nitrate source.

[00154] A botanical nitrate source is any plant matter, extract of plant matter, or product of plant matter containing nitrate. Generally, it is desirable that the botanical nitrate source be generally regarded as safe for human or animal consumption. In one embodiment, the botanical nitrate source is selected from the group consisting of beet root, artichoke, holy basil, gymnema sylvestre, L9H, ashwagandha root, salvia, St. John wort, broccoli, stevia, spinach, gingko, kelp, tribulus, eleuthero, epimedium, eucommia, hawthorn berry, rhodiola, green tea, codonopsys, panax ginseng, astragalus, pine bark, dodder seed, Schisandra, cordyceps, and mixtures thereof. In one particular embodiment, the botanical nitrate source is selected from the group consisting of beet root, artichoke, holy basil, gingko, and mixtures thereof.

[00155] In another embodiment, the botanical nitrate source is a beet root extract.

[00156] In one embodiment of the synergistic composition, the beet root extract comprises from about 5 wt % to about 90 wt % of the claimed composition. In another embodiment of the composition, the beet root extract comprises from about 10 wt % to about 80 wt % of the claimed composition. In another embodiment of the composition, the beet root extract comprises at least 10, 15, 20, 25, 30, 35, 40, 45, 50 wt % or more of the claimed composition.

[00157] In another embodiment, the synergistic composition comprises at least the active ingredients citrulline, glutathione, ornithine, beet root extract and citicoline, in varying concentrations.

[00158] In another embodiment, the synergistic composition comprises at least the active ingredients citrulline, glutathione, ornithine, beet root extract, citicoline, and at least one flavan-3-ol compound. In another embodiment, the at least one flavan-3-ol compound is selected from the group consisting of monomers, oligomers, polymers, glycosides and pharmaceutically acceptable salts of the following: (+)-catechin, (-)-epicatechin, epigallocatechin, epicatechin gallate, epigallocatechin gallate, epiafzelechin, and fisetinidol. In another embodiment, the at least one flavan-3-ol compound is provided in the form of a green tea extract, grape seed extract, cocoa extract or mixtures thereof.

[00159] In another embodiment, the synergistic composition comprises at least the active ingredients citrulline, glutathione, ornithine, beet root extract, citicoline, and one or more additional active ingredients selected from the group consisting of a catechin, an epicatechin, and an extract comprising one or more catechin and/or epicatechin.

[00160] The four types of catechins (or epicatechins) found in green tea (from Camellia sinensis ) are the epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin gallate (ECG), and epicatechin (EC). EGCG accounts for about 50-80% of the catechins in green tea. Catechins may also be found from other sources such as cocoa.

[00161] In one or more embodiments, the synergistic composition comprises an extract from Camellia sinensis or a green tea containing a catechin selected from the group consisting of epigallocatechin gallate, epigallocatechin, epicatechin gallate, epicatechin and combinations thereof, in varying concentrations.

[00162] The catechin can be, but is not limited to, catechin monomers (e.g., flavan-3-ol monomers), catechin isomers, and combinations thereof. Some embodiments comprise catechin esters, such as catechin gallate (CG), gallocatechin (GC), gallocatechin gallate (GCG), epicatechin (EC), epicatechin gallate (ECG), epigallocatechin (EGC), and epigallocatechin gallate (EGCG), and combinations of two or more thereof.

[00163] Catechins can be derived from a variety of sources, such as tea plants (e.g., Camellia sinensis), cocoas (e.g., made from seeds of Theobroma cacao), and chocolates. In some embodiments, the catechins are extracted from a plant, such as a green tea plant (e.g., Camellia sinensis).

[00164] Some embodiments comprise a plant extract that comprises catechins. In some embodiments, the plant extract comprises more than about 70% (w/w) catechins, more than about 80% (w/w) catechins, more than about 90% (w/w) catechins, or more than about 95% (w/w) catechins. In some embodiments, the plant extract comprises more than 70% (w/w) catechins, more than 80% (w/w) catechins, more than 90% (w/w) catechins, or more than 95% (w/w) catechins.

[00165] In some embodiments, the plant extract is a green tea extract. The extract can be of any suitable green tea variety, such as sencha, fukushami sencha, gyokuro, kabusecha, matcha, tencha, genmaicha, hojicha, shincha, ichibancha, nibancha, or sanbancha.

[00166] In some embodiments, the composition comprises from about 250 mg to about 1,500 mg green tea extract comprising at least 20, 30, 40, 50, 60, 70, 80, or 90% (w/w) catechins.

[00167] In one or more embodiments, the composition comprises as an active ingredient a green tea extract containing (-)-gallocatechin gallate (GCG) at 5 to 25% by weight based on a total weight of the composition or the extract and (-)-epigallocatechin gallate (EGCG) at 7 to 15% by weight based on the total weight of the composition or the extract.

[00168] In another embodiment, the composition comprises at least the active ingredients citrulline, glutathione, ornithine, beet root extract, citicoline, green tea extract, and one or more vitamins, in varying concentrations.

[00169] In one example, the citrulline, glutathione and ornithine in the composition, can include glutathione, L-citrulline and ornithine, or a combination thereof. In one example, the glutathione, L-citrulline and ornithine can comprise from about 40 wt % to about 98 wt % of the composition. In another example, the glutathione, L-citrulline and ornithine can comprise from 10 wt % to 60 wt % of the composition.

[00170] In another example, the glutathione, L-citrulline and ornithine each comprise from about 10 wt % to about 90 wt % of the composition. In another example, the glutathione, L- citrulline and ornithine each comprise from about 15 wt % to about 80 wt % of the composition. In another example, the glutathione, L-citrulline and ornithine each comprise from about 20 wt % to about 70 wt % of the composition. In another example, the glutathione comprises at least 10, 15, 20, 25, 30, 35, 40, 45, 50 wt% or more of the composition. In another example, the L- citrulline comprises at least 10, 15, 20, 25, 30, 35, 40, 45, 50 wt% or more of the composition. In another example, the ornithine comprises at least 10, 15, 20, 25, 30, 35, 40, 45, 50 wt% or more of the composition.

[00171] The L-isomer of citrulline can boost nitric oxide levels, which can increase blood flow and reduce fatigue by replenishing depleted nutrients. In one example, a supplement formulation can include citrulline at from about 1 wt % to about 45 wt %. In other examples, supplement formulations can include citrulline at from about 10 wt % to about 20 wt %, at from about 5 wt % to about 20 wt %, at from about 10 wt % to about 25 wt %, at from about 10 wt % to about 30 wt %, at from about 5 wt % to about 25 wt %, at from about 10 wt % to about 30 wt %, or at from about 5 wt % to about 15 wt %.

[00172] In one or more embodiments, the citrulline includes derivatives thereof, such as citrulline malate, and the like. Supplement formulations containing both malic acid and citrulline can include these ingredients in any beneficial relative amount, and such can be varied depending on the forms of malic acid and citrulline used, and to suit individual needs. Non limiting examples of ratios of malic acid to citrulline include a 1 : 1 ratio, a 1 :2 ratio, a 1 :3 ratio, a 1 :4 ratio, a 1 :5 ratio, a 1.5: 1 ratio, a 2: 1 ratio, a 3 : 1 ratio, and the like. In one example, the malic acid and citrulline can be present at a 1 :2 ratio.

[00173] In one or more embodiments, the glutathione includes derivatives thereof, such as glutathione disulfide, and the like.

[00174] In another embodiment, the L-citrulline can be present in the composition from about 1 wt % to about 80 wt %. In another example, the L-citrulline can be present in the composition from about 0.5 wt % to about 90 wt %. In yet another example, the L-citrulline can be present in the composition from about 0.25 wt % to about 95 wt %. In a further example, the L-citrulline can be present in the composition from about 0.125 wt % to about 99 wt %. In yet a further example, the L-citrulline can be present in the composition from about 0.1 wt % to about 50 wt %. In yet another example, the L-citrulline can be present from about 0.5 wt % to about 25 wt %.

[00175] In one or more embodiments, the glutathione includes derivatives thereof, such as glutathione disulfide, and the like.

[00176] In one or more embodiments, the glutathione comprises glutathione (L-Glutamyl-L- Cysteinyl-Glycine, Glu-Cys-Gly). The glutathione may be in its reduced form with a free thiol group (GSH) or in its oxidized form with a disulfide bond (GSSG). In one preferred embodiment, the oligopeptide is oxidized glutathione (GSSG). Under appropriate circumstances, as will be understood by one with ordinary skill in the art, in order to help achieve the above-mentioned benefits, it is desirable to include a different oligopeptide such as glutathione oxidized or reduced or Peptide T.

[00177] In certain embodiments the composition is provided in a dose form comprising reduced glutathione provided in a range selected from: 100 to 900 mg; 150 to 850 mg; 200 to 800 mg; 250 to 800 mg; 300 to 700 mg; 400 to 700 mg; 400 to 600 mg; 450 to 550 mg; or about 500 mg.

[00178] The ratio of the weight percentage of citrulline and glutathione can also vary. In one embodiment, the citrulline and glutathione can be present in the composition at a weight percent concentration ranging from about 1 :5 to about 20: 1, respectively. In another embodiment, the citrulline and glutathione can be present in the composition at a weight percent concentration ranging from about 2.5: 1 to about 15: 1, respectively. In another embodiment, the citrulline and glutathione can be present in the composition at a weight percent concentration ranging from about 5: 1 to about 15: 1, respectively. In another embodiment, the citrulline and glutathione can be present in the composition at a weight percent concentration ranging from about 8: 1 to about 12: 1, respectively. In yet another embodiment, the citrulline and glutathione can be present in the composition at a weight percent concentration of about 10: 1, respectively.

[00179] In one or more embodiments, the composition comprises 4-8g citrulline, 400-800mg glutathione, and 0.3-8g ornithine. In one or more embodiments, the composition comprises 6- 8g citrulline, 500-700mg glutathione, and 0.5-2g ornithine.

[00180] In another embodiment, the dose of the active ingredient may be 5 mg/kg/day to 1000 mg/kg/day on a dry weight basis. In one aspect, the dose may be 5 mg/kg/or more, 100 mg/kg/or more, 200 mg/kg/or more, 300 mg/kg/or more, 400 mg/kg/or more, 500 mg/kg/or more, 600 mg/kg/or more, 700 mg/kg/or more, 800 mg/kg/or more, or 900 mg/kg/or more. In another aspect, the dose may be 1000 mg/kg/or less, 900 mg/kg/or less, 800 mg/kg/or less, 700 mg/kg/or less, 600 mg/kg/or less, 500 mg/kg/or less, 400 mg/kg/or less, 300 mg/kg/or less, 200 mg/kg/or less, 100 mg/kg/or less, 50 mg/kg/or less, or 10 mg/kg/or less.

[00181] In some embodiments, the supplement comprises at least about 200 mg vitamin C (ascorbic acid), such as at least about 300 mg, at least about 500 mg, at least about 750 mg, at least about 1000 mg, at least about 1250, at least about 1500, or at least about 2000 mg of vitamin C. In some embodiments, the supplement comprises 200mg, 500 mg, 750 mg, 1000 mg, 1250, 1500, 2000 or 3000 mg of vitamin C. In some embodiments, the dietary supplement comprises about 200-3000 mg, from about 400-2000 mg, about 500-1000 mg of vitamin C. [00182] Muscle Metabolism Formulation

[00183] Some embodiments of the present disclosure provide for methods and compositions for improved muscle metabolism. Some embodiments of the present disclosure provide for methods and compositions for improved muscle recovery after exercise. Some embodiments of the present disclosure can be consumed daily for its preventive health benefits or as needed before or after intense physical activity.

[00184] In one or more embodiments, the synergistic composition for improved muscle metabolism and exercise recovery comprises at least the active ingredients ecdysterone or ecdysteroid-containing compounds and extracts, citrulline, glutathione and ornithine.

[00185] In another embodiment, the synergistic composition for improved muscle metabolism and exercise recovery comprises at least the active ingredients ecdysterone or ecdysteroid-containing compounds and extracts, citrulline, glutathione, ornithine and lycopene.

[00186] In another embodiment, the synergistic composition for improved muscle metabolism and exercise recovery comprises at least the active ingredients ecdysterone or ecdysteroid-containing compounds and extracts, citrulline, glutathione, ornithine, and one or more additional active ingredients selected from the group consisting of a source of nitric oxide, citicoline, a flavan-3-ol compound, and an anti-oxidant.

[00187] In another embodiment, the synergistic composition for improved muscle metabolism and exercise recovery comprises at least the active ingredients ecdysterone or ecdysteroid-containing compounds and extracts, citrulline, glutathione, ornithine, a source of nitric oxide, citicoline, a flavan-3-ol compound, and an anti-oxidant.

[00188] In one or more embodiments, the present invention provides for methods of administering to a mammal in need of treatment a composition comprising an ecdysteroid wherein the concentration of ecdysteroid is sufficient to increase growth hormone transcription in tissue. It is further contemplated that for the methods of treatment the administration of the composition includes all modes known in the art for delivering therapeutic compositions to a mammal. In one or more embodiment, the composition can be orally administered.

[00189] In one or more embodiments, the ecdysteroid is a phytoecdy steroid.

Phytoecdysteroids, sometimes called phytoecdysones, are plant-derived eedysteroids. In another embodiment, the phytoecdy steroid is synthesized by plants or an ecdysteroid synthesized by members of the phylum arthropoda or a synthetic version thereof. In another embodiment, the ecdysteroid is 20-hydroxyecdysone (20HE). In another embodiment, the ecdysteroid composition can be a plant extract. In one embodiment, the ecdysteroid composition can be an extract of spinach. In one or more embodiments, the phytoecdysones that are used can be obtained by extraction from plants and fungi. Some plants or fungi that produce phytoecdysteroids include Achyranthes bidentata, Tinospora cordifolia, Pfaffia paniculata, Leuzea carthamoides, Rhaponticum uniflorum, Serratula coronata, Cordyceps, spinach and asparagus. Ecdysones prepared by hemisynthesis can also be used. In one or more embodiments, the phytoecdysones are selected from 20-hydroxyecdysone, makisterone A, 24-epimakisterone A, 24(28)- dehydromakisterone A, 20,26-dihydroxyecdysone, and combinations of two or more of these components.

In one or more embodiments, the phytoecdysones can be in pure form or contained in a more or less enriched plant extract. Advantageously, the phytoecdysones implemented according to the invention are in the form of a plant extract enriched with phytoecdysones, with the extract containing at least 1% phytoecdysones by weight. In one or more embodiments, the extract contains between 1% and 50% phytoecdysones, between 1% and 20% phytoecdysones, between 1.5% and 10%, and greater than 2% phytoecdysones by weight.

[00190] In one or more embodiments, the food plants from which the extracts according to the invention come are advantageously selected from chenopodiacae, particularly quinoa and spinach (Findeisen, 2004). Medicinal plants can also be used to develop extracts that are rich in phytoecdysones.

[00191] In one or more embodiments, a plant extract enriched with phytoecdysones according to the invention comes from quinoa. Quinoa is an edible pseudo-cereal that is rich in phytoecdysones (Zhu et ah, 2001; Dini et al., 2005). It is thus possible to supplement food by ingesting extract of quinoa that has been enriched with phytoecdysones, by consuming it as a dietary supplement, such as in the form of a capsule. Quinoa is currently known as the food plant that is the richest in phytoecdysones. Quinoa seeds contain a blend of phytoecdysones (Zhu et ak, 2001).

[00192] In one or more embodiments, the phytoecdysones are orally administered at a rate of 0.25 to 10, 0.5 to 7.5, or 1 to 5 mg per kg of body weight per day. In another embodiment, the

[00193] In one or more embodiments, the ecdysteroid is present in a dosage of 10 to 5000 mg. In another embodiment, the ecdysteroid is present in a dosage of at least 10, 25, 50, 100, 250, 500, 750, 1000, 1250, 1500, or 2000 mg or more. In another embodiment, the ecdysteroid is present in a dosage of at most 500, 750, 1000, 1250, 1500, 2000, 2500, 3000, 3500, 4000, 4500, 5000 mg or less. [00194] In some embodiments, the ecdysteroid comprises at a daily dose of about 1-5000 mg/day, preferably at about 30-1000 mg/day, more preferably about 50-1000 mg/day, and even more preferably about 100-900 mg/day or 200-800 mg/day. In some embodiments, the ecdysteroid comprises multiple daily doses of 10, 50, 100, 200, 300, 400, 500, 600, 700, 800 or more mg per dose.

[00195] In one or more embodiments, the synergistic composition comprises at least the active ingredients ecdysteroid or ecdysteroid extract, citrulline, glutathione and ornithine in varying concentrations. In one or more embodiments, the synergistic composition comprises at least the active ingredients ecdysteroid or ecdysteroid extract, citrulline, glutathione, ornithine and lycopene in varying concentrations.

[00196] In one or more embodiments, the synergistic composition comprises at least the active ingredients ecdysteroid or ecdysteroid extract, citrulline, glutathione, ornithine, and one or more additional active ingredients selected from the group consisting of a source of nitric oxide, citicoline, a flavan-3-ol compound, and an anti-oxidant in varying concentrations. In one or more embodiments, the synergistic composition further comprises one or more vitamins.

[00197] In another embodiment, the synergistic composition comprises at least the active ingredients ecdysteroid or ecdysteroid extract, citrulline, glutathione, ornithine, a source of nitric oxide, citicoline, a flavan-3-ol compound, and an anti-oxidant in varying concentrations, in varying concentrations.

[00198] In one or more embodiments, the synergistic composition can include a source of nitric oxide selected from the group consisting of beet root extract, vitamin Bl, collard green extract, nut powders, spinach extract, broccoli extract, lettuce extract, celery, kale, watercress, carrot, arugula, mustard greens, or a combination thereof.

[00199] In one or more embodiments, the invention includes compositions having (i) at least 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 15%, 20%, 25%, 30%, 35%, 40% ecdy steroids including, for example, about 0.5 to 20% ecdysteroids or about 0.4% to 5% ecdysteroids.

[00200] In some embodiments the composition comprises at least 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 15%, 20%, or 25% of 20- hydroxy ecdysone including, for example, 0.2% to 10% of 20-hydroxy ecdysone.

[00201] In one aspect, the invention the ecdysteroid or ecdysteroid extract includes a composition including a Rhaponticum extract. In some embodiments, the Rhaponticum extract comprises at least 0.01%, 0.05%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 15%, 20%, or 25% ecdysteroids including, for example, about 0.1 to 10% ecdysteroids or about 0.4% to 5% ecdysteroids. In some embodiments the Rhaponticum extract composition comprises at least 0.01%, 0.05%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 15%, 20%, or 25% of 20- hydroxyecdysone including, for example, 0.1% to 5.0% of 20-hydroxyecdysone.

[00202] In some embodiments, the Rhaponticum extract comprises at least 0.01%, 0.05%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 15%, 20%, or 25% ecdysteroids including, for example, about 0.1 to 10% ecdysteroids or about 0.4% to 5% ecdysteroids. In some embodiments the composition comprises at least 0.01%, 0.05%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 15%, 20%, or 25% of 20-hydroxyecdysone including, for example, 0.1% to 5.0% of 20- hydroxyecdysone.

[00203] The extract of Rhaponticum may be derived from any Rhaponticum species including (but not limited to) Rhaponticum acaule (L.) DC., Rhaponticum aulieatense Iljin, Rhaponticum australe (Gaudich.), Rhaponticum berardioides (Batt.), Rhaponticum canariense DC., Rhaponticum carthamoides (Willd.), Rhaponticum coniferum (L.) Greuter, Rhaponticum cossonianum (Ball) Greuter, Rhaponticum cynaroides Less., Rhaponticum exaltatum (Willk.) Greuter, Rhaponticum fontqueri, Rhaponticoides hajastana (Tzvelev) M. V. Agab. & Greuter, Rhaponticum heleniifolium Godr. & Gren., Rhaponticoides iconiensis (Hub-Mor.) M. V. Agab. & Greuter, Rhaponticum insigne (Boiss.) Wagenitz, Rhaponticum integrifolium C. Winkl., Rhapontikum karatavicum Iljin, Rhaponticum longifolium (Hoffmanns. & Link) Dittrich, Rhaponticum lyratum C. Winkl. ex Iljin, Rhaponticum namanganicum Iljin, Rhaponticum nanum Lipsky, Rhaponticum nitidum Fisch, Rhaponticum pulchrum Fisch. & C. A. Mey. Rhaponticum repens (L.) Hidalgo, Rhaponticum scariosum Lam., Rhaponticum serratuloides (Georgi) Bobrov, Rhaponticum uniflorum (L.) DC. In some embodiments, the herbal extract of Rhaponticum is made from a plant selected from the family of Asteraceae, the genus Rhaponticum and more specifically the specie Rhaponticum Carthamoides.

[00204] In some embodiments, the extract of Rhaponticum comprises at least 0.01% total ecdysteroids, about 0.05% to 99%, 98%, 97%, 96%, 95%, 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, or 10% total ecdysteroids based on the total weight of the extract (w/w), more preferably at least about 0.1 to 20%, 0.5 to 15%, 0.5 to 10% or 1 to 5% total ecdysteroids, most preferably 0.4% to 5% total ecdysteroids based on the total weight of the extract (w/w). In some embodiments, the extract of Rhaponticum comprises at least 0.01% 20-hydroxyecdysone (20HE) based on the total weight of the extract (w/w), about 0.05% to 99%, 98%, 97%, 96%, 95%, 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, or 10% 20HE, more preferably at least about 0.01%, 0.05%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 15%, 20%, or 25% 20HE based on the total weight of the extract (w/w).

[00205] In addition, the extract of Rhaponticum may also comprise ecdysteroids other than ecdysterone, such as by way of a non-limiting example, the following ecdysteroids: polypodine B, Makisterone A, 2-Deoxyecdysterone, Integristerone A, Integristerone B, Taxisterone, Ajugasterone C, . alpha. -ecdysone, Lesterone, Rapisterone D, Inokosterone, Rapisterone, 20- hydroxyecdysone 2,3;20,22-diacetonide, 20-hydroxyecdysone 2,3-monoacetonide; 20- hydroxyecdysone 20,22-monoacetonide; 22-oxo-20-hydroxy ecdysone, 24(28)- dehydromakisterone A; (24z)-29-hydroxy-24(28)-dehydromakisterone C; carthamosterone; rubrosterone, dihydrorubrosterone; posterone, isovitexirone, leuzeasterone, makisterone C, polypodine B 20,22-acetonide; rapisterone B, rapisterone C, rapisterone D 20-acetate, 24(24')(z)-dehydroamarasterone B, polypodine B-22-benzoate; carthamosterone A, carthamosterone B; Amarasterone A; carthamoleusterone; 24(28)-dehydroamarasterone B, 22- deoxy-28-hydroxymakisterone C; 3 -epi-20-hydroxy ecdysone; 24-epi -makisterone A, 14-epi- ponasterone A 22-glucoside; 5-.alpha.-20-hydroxyecdysone; 20-hydroxyecdysone 2-acetate, 20-hydroxyecdysone 3-acetate; l .beta.-hydroxymakisterone C; 26-hydroxymakisterone C; 15- hydroxyponasterone A; inokosterone 20,22-acetonide, turkestone.

[00206] The extract of Rhaponticum may also comprise the following ecdysteroids: abutasterone25-acetoxy-20-hydroxyecdysone 3-o-; beta; -d-glucopyranoside; acetylpinnasterol; achyranthesterone; ajugacetalsterone a; ajugacetalsterone b; ajugalide e; ajugasterone b; ajugasterone b; ajugasterone c 3; 22-diacetonide; ajugasterone c 22-ethylidene; acetal; ajugasterone c 22-monoacetonide; ajugasterone d; amarasterone a; amarasterone b; asteraster b; atrotosterone a; atrotosterone b; atrotosterone c; blechnoside a; blechnoside b; bombycosterol; bombycoster 3-phosphate; brahuisterone; calonysterone; calvaster a; calvaster b; canescensterone; capitasterone; carpesterol; castasterone; cheilanthone a; cheilanthone b; coronatasterone; cyanosterone a; cyasterone; cyasterone 3 -acetate; cyasterone 22-acetate; cyasterone 3-monoacetonide; cyathisterone; dacryhainansterone; decumb ester one a; dehydroajugalactone; dehydroajugalactone; dehydroamarasterone b; dehydrocyasterone 2- glucoside; 3-dehydroecdysone; 2-dehydro-3-epi-20-hydroxyecdysone; and/or 22-dehydro- 12- hydroxy cyasterone, dehydro-20-hydroxy ecdysone; 3 -dehydro-20-hydroxy ecdysone; dehydro- 242-hydroxymakisterone c dehydro- 12-hydroxy -29-nor-cyasterone; dehydro- 12-hydroxy -29- nor-sengosterone; dehydro- 12-hydroxy-sengosterone; (28)-dehydromakisterone a; 2- dehydropoststerone; 24-dehydroprecyasterone; 2-deoxy castasterone; 22-deoxy-21- dihydroxyecdysone; 22-deoxy-26-dihydroxyecdysone; 2-deoxy-26-dihydroxyecdysone; 3- deoxy-1 (alpha) 20-dihydroxy ecdysone; 2-deoxy-20-dihydroxyecdysone 2-deoxy-polypodine b; 2-deoxyecdysone; deoxy ecdysone; 2-deoxyecdysone 3-acetate; 2-deoxy ecdysone 22- acetate; 2-deoxyecdysone 22-adenosine-monophosphate; 2-deoxyecdysone 22-benzoate; 2- deoxy ecdysone 3-4-(l-(beta)-d-glucopyranosyl)-ferulate; 2-deoxyecdysone 22-(beta)-d- glucoside; 25-deoxyecdysone 22-o-(beta)-d-glucopyranoside; 2-deoxyecdysone 22-phosphate;

2-deoxyecdysone 25-rhamnoside; (5(alpha))-2-deoxy-21 -hydroxy ecdysone; 2-deoxy -20- hydroxyecdysone; 22-deoxy-26-hydroxyecdysone; 14-deoxy -20-hydroxy ecdysone; 2-deoxy-

21 -hydroxy ecdysone; 2-deoxy -20-hydroxy ecdysone 25-acetate; 2-deoxy -20-hydroxy ecdysone

22-acetate; (5(alpha))-2-deoxy-20-hydroxyecdysone 3-acetate; 2-deoxy-20-hydroxyecdysone

3-acetate; 2-deoxy-20-hydroxyecdysone 22-benzoate; and/or 2-deoxy-20-hydroxyecdysone 3- crotonate.

[00207] In one or more embodiments, the disclosed synergistic compositions comprise embodiments wherein ecdysterone or one or more ecdysteroid-containing compound or extract is present in 10-5000 mg, 10-3000 mg, 10-2000 mg, 10-1000 mg, 20-900 mg, 50-900 mg, 100- 800 mg, or 200-800 mg.

[00208] In one or more embodiments, the disclosed compositions comprise embodiments wherein citrulline is present as L-citrulline DL-malate 2: 1, which combines two parts L- citrulline with one-part DL-malic acid, wherein citrulline is present in 2-10 g, 4-9g, 5-9 g, 6-8 g, or 8 g.

[00209] In various embodiments, the citrulline dosage can be modified based on the type of subject and/or the mass of the subject. For example, in some embodiments a suitable dosage for a human subject can be 50-2000 mg/day or 200-500 mg/day. In some embodiments, a desirable dosage for a human subject or ruminant subject can be 5-50 mg/kg/day or less than 200 mg/kg/day.

[00210] In yet another aspect, a method for improving muscle mass and muscle strength in a mammal is provided, comprising administering to the mammal an effective amount of the composition described herein. The mammal is preferably a human, more preferably an athlete. In a further aspect of the disclosure, a method for promoting aerobic and anaerobic sport/physical performance in a mammal is provided, comprising administering to the mammal an effective amount of the composition disclosed herein. In yet another aspect, a method for treating conditions associated with or characterized by muscle atrophy in a mammal is provided, comprising administering to the mammal an effective amount of the composition described herein. [00211] In some embodiments, the composition is orally administered to a mammal, preferably a human, at a daily dose of about 1-5000 mg/day, preferably at about 30-1000 mg/day, more preferably about 50-1000 mg/day, and even more preferably about 100-600 mg/day or 200-500 mg/day. Lower doses of about 0.5 mg/day or a dose higher than 5000 mg/day may be provided. In some embodiments, multiple daily doses of 10, 50, 100, 200, 300, 400, 500, 600, 700, 800 or more mg per dose are provided.

[00212] In some embodiments, the subject is administered a daily dose of at least 1 mg/kg/day, 5 mg/kg/day, 10 mg/kg/day, 20 mg/kg/day, 30 mg/kg/day, 40 mg/kg/day, 50 mg/kg/day, 75 mg/kg/day, 100 mg/kg/day, 200 mg/kg/day, 400 mg/kg/day, 600 mg/kg/day, 800 mg/kg/day, 1000 mg/kg/day, 2000 mg/kg/day, 3000 mg/kg/day, 5000 mg/kg/day or more per day. In one embodiment, the oral formulation is about 30-1000 mg/kg/day. In another embodiment, the oral formulation is about 50-100 mg/kg/day, about 5-50 mg/kg/day, or less than 200 mg/kg/day. In further embodiments, the oral formulation can be about 200-500 mg/day, or about 50-2000 mg/day. The total daily dose may be administered as a unitary dosage or split into multiple dosages administered at different times (e.g., twice, three times, four times, or more per day).

[00213] In one or more embodiments, the disclosed synergistic compositions comprise embodiments wherein citrulline is present in 2-10 g, 4-9g, 5-9 g, 6-8 g, or 8 g. In one or more embodiments, the disclosed compositions comprise embodiments wherein citrulline is present as L-citrulline DL-malate 2: 1, which combines two parts L-citrulline with one part DL-malic acid, wherein citrulline is present in 2-10 g, 4-9g, 5-9 g, 6-8 g, or 8 g.

[00214] In one or more embodiments, the disclosed compositions comprise embodiments wherein glutathione is present in 300-1200 mg, 400-1000 mg, 500-900 mg, 600-800 mg, or 800 mg. In one or more embodiments, the disclosed compositions comprise embodiments wherein glutathione is present as reduced glutathione and is present in 100 to 1500 mg; 150 to 1200 mg; 200 to 1100 mg; 250 to 1000 mg; 300 to 950 mg; 400 to 900 mg; 450 to 850 mg; 500 to 800 mg; or 800 mg.

[00215] In one or more embodiments, the disclosed compositions comprise embodiments wherein ornithine is present in 0.1-12 g, 0.2-10 g, 0.3-8g, 0.4-2 g, 0.5-1 g, 0.7-0.9 g or 0.8 g. In one or more embodiments, the disclosed compositions comprise embodiments wherein ornithine is present as L-orni thine HC1.

[00216] In one or more embodiments, the disclosed compositions comprise embodiments wherein a source of nitric oxide is present in 100-1000 mg, 200-800 mg, 300-700 mg, 350-600 mg, 350-500 mg, or 400 mg. [00217] In one or more embodiments, the disclosed compositions comprise embodiments wherein the source of nitric oxide is beet root extract. In one or more embodiments, the disclosed compositions comprise embodiments wherein beet root extract is present in 100- lOOOmg, 200-800 mg, 300-700 mg, 350-500 mg, or 400 mg.

[00218] In one or more embodiments, the disclosed compositions comprise embodiments wherein citicoline is present in 200-800 mg, 350-600 mg, 450-550 mg or 500 mg.

[00219] In one or more embodiments, the disclosed compositions comprise embodiments wherein at least one flavan-3-ol compound is present. In one or more embodiments, the at least one flavan-3-ol compound is selected from the group consisting of monomers, oligomers, polymers, glycosides and pharmaceutically acceptable salts of the following: (+)-catechin, (-)- epicatechin, epigallocatechin, epicatechin gallate, epigallocatechin gallate, epiafzelechin, and fisetinidol. In one or more embodiments, the disclosed compositions comprise embodiments wherein at least one flavan-3-ol compound is present in 200-800 mg, 300-700 mg, 400-600 mg, 500-600 mg or 500 mg.

[00220] In one or more embodiments, the disclosed compositions comprise embodiments wherein green tea extract is present in 200-800 mg, 300-700 mg, 400-600 mg, 500-600 mg or 500 mg; and wherein the green tea extract comprises at least 10%, 15%, 20%, 25%, 30%, 35%, 40% epigallocatechin gallate (EGCG), or more.

[00221] In one or more embodiments, the disclosed compositions comprise embodiments wherein at least one anti-oxidant is present. In one or more embodiments, the at least one anti oxidant is selected from the group consisting of idebenone, co-enzyme Q10, vitamin E, ALA (Alpha Lipoic Acid), vitamin C, carnosine, tocotrienols, flavonoids, ALC, vinpocetine, selenium, lycopene, creatine, arginine, taurine, cysteine, NADH, resveratrol, resveratrol- arginine conjugate (ResArgin), ginkgo biloba, oligomeric proanthocyanidins, and phenolic antioxidants and folic acid, folate, folinic acid and tetrahydrofolate.

[00222] In one or more embodiments, the at least one anti-oxidant is lycopene. In one or more embodiments, the disclosed compositions comprise embodiments wherein lycopene is present in a range selected from: 5 to 90 mg; 10 to 85 mg; 15 to 80 mg; 20 to 80 mg; 20 to 70 mg; or 20 to 40 mg.

[00223] In one or more embodiments, the disclosed compositions comprise embodiments wherein at least one vitamin, mineral or nutritional supplement is present. In one or more embodiments, the at least one vitamin, mineral or nutritional supplement is selected from the group consisting of vitamin B complex, folic acid, niacin, niacinamide, pantothenic acid, pyridoxine HCL, vitamin B2, folate, biotin, vitamin C, vitamin D, vitamin D3, vitamin E, vitamin K, cyanocobalamin, inositol, thiamine, thiamine mononitrate, calcium pantothenate, mixed tocopherols, d-alpha tocopheryl acetate, magnesium, calcium, calcium carbonate, calcium chelate, calcium di-phosphate, calcium phosphate, iron, magnesium carbonate, magnesium citrate, magnesium oxide, magnesium phosphate, manganese chelate, manganese sulfate, potassium, potassium chelate, potassium chloride, sodium, zinc, vanadyl sulphate, chromium, chromium chloride, chromium picolinate, and chromium polynicotinate.

[00224] In this regard, suitable concentrations for a number of anti-oxidant agents in the various embodiments of the present invention are as follows: Vitamin E (d-alpha-tocopheryl acetate): 40 to 4000 I.U, with a usual range of 200 to 1200 I.U., and typically 200 to 600 I.U. Vitamin C (ascorbic acid or a salt thereof): 100 to 3000 mg, with a usual range of 200 to 1000 mg. Lycopene: 5 to 90 mg, with usual ranges of 10 to 80 mg, and 20 to 60 mg. Co-Enzyme Q10: 4 to 400 mg, with a usual range of 10 to 100 mg. Selenium: 10 to 250 pg, with a usual range of 20 to 50 pg. Zinc: 2.5 to 100 mg, with a usual range of 10 to 50 mg. Glutathione: 100 to 1000 mg, with a usual range of 400 to 600 mg. L-carnitine: 1 to 5 grams, with a usual range of 2 to 3 grams. Pentoxifylline: 200 to 1500 mg, with a usual range of 300 to 1200 mg.

[00225] In one or more embodiments, the disclosed compositions comprise embodiments wherein vitamin C is present in 200-3000 mg, 400-2000 mg, 500-1000 mg or 500-800 mg of vitamin C.

[00226] In one or more embodiments, the disclosed compositions comprise embodiments wherein the citrulline is present in a 1 :5 to 20: 1 ratio, 2.5: 1 to 15: 1 ratio, 5: 1 to 15: 1 ratio, 8: 1 to about 12: 1 ratio, 9: 1 to about 11 : 1 ratio or 10: 1 ratio with the glutathione.

[00227] In one or more embodiments, the disclosed compositions may further comprise inositol-stabilized arginine silicate (also known as "arginine silicate," "arginine silicate inositol," and "ASI”). In one or more embodiments, the disclosed compositions comprise embodiments wherein inositol-stabilized arginine silicate is present in a therapeutically effective amount of about 2-5,000 mg, 250-2,500 mg, 500-2,000 mg or 500 mg-1,000 mg. In one or more embodiments, the disclosed compositions comprise embodiments wherein inositol-stabilized arginine silicate is administered in a therapeutically effective amount per kg body weight per day of about 1 mg/kg, 1.5mg/kg, 2.0 mg/kg, 2.5 mg/kg, 3 mg/kg, 4.0 mg/kg, 5.0 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 25 mg/kg, 30 mg/kg, 35 mg/kg, 40 mg/kg, 45 mg/kg 50 mg/kg, 55 mg/kg, 60 mg/kg, 65 mg/kg, 70 mg/kg, 75 mg/kg, 80 mg/kg, 85 mg/kg, 90 mg/kg, 95 mg/kg, 100 mg/kg, 125 mg/kg, 150 mg/kg, 200 mg/kg, 250 mg/kg, 300 mg/kg, 350 mg/kg, 400 mg/kg, 450 mg/kg, 500 mg/kg, 550 mg/kg, 600 mg/kg, 650 mg/kg, 700 mg/kg, 750 mg/kg, 800 mg/kg, 850 mg/kg, 900 mg/kg, 950 mg/kg, 1 g/kg, 5 g/kg, 10 g/kg, or more. A commercially available, bioavailable form of inositol- stabilized arginine silicate is available in purified form as Nitrosigine® from Nutrition 21 (Purchase, NY) and Glanbia Nutritionals, Inc. (Carlsbad, CA).

[00228] In one or more embodiments, the disclosed compositions may further comprise creatine or creatine derivatives. In one or more embodiments, the disclosed compositions comprise embodiments wherein creatine, a creatine derivative or mixtures thereof is present in a therapeutically effective amount of about 0.1-10 g, 0.5-5 g, 0.9-2.5 g or 1-1.5 g of creatine or creatine derivative. Creatine and creatine derivatives are widely available from a number of commercial sources. Commercially available creatine derivatives include creatine phosphate, creatine citrate, magnesium creatine, alkaline creatine, creatine pyruvate, creatine hydrates (including, but not limited to creatine monohydrate), and creatine malate. Glycocyamine, an in vivo precursor of creatine, is also commercially available and suitable in the practice of the present invention. The supplement preferably comprises creatine malate or creatine monohydrate.

[00229] In one or more embodiments, the disclosed compositions may further comprise a Rhodiola extract. In some embodiments, the Rhodiola extract comprises at least 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 15%, 20%, or 25% salidrosides including, for example, about 1% to 4%. In some embodiments, the Rhodiola extract composition comprises at least 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 15%, 20%, or 25% rosavins including, for example, about 3% to 6% rosavins. In some embodiments, the composition comprises at least 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 15%, 20%, or 25% rosavin including, for example, about 2% to 5% rosavin or 1% to 5% rosavin. In some embodiments, the Rhodiola extract composition comprises at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 99% Rhodiola extract including, for example about 50% to 99%, 60%-95%, 70%-95% Rhodiola extract.

[00230] In one or more embodiments, the Rhodiola extract comprises at least 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 15%, 20%, or 25% salidrosides including, for example, about 1% to 4%. In some embodiments, the composition comprises at least 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 15%, 20%, or 25% rosavins including, for example, about 3% to 6% rosavins. In some embodiments, the composition comprises at least 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 15%, 20%, or 25% rosavin including, for example, about 2% to 5% rosavin. In one or more embodiments, the composition comprises at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 99% Rhodiola extract including, for example about 50% to 99%, 60%-95%, 70%-95% Rhodiola extract.

[00231] Health and Medical Formulations

[00232] In one or more embodiments, the composition comprises at least the active ingredients citicoline (also known as CDP-choline; cytidine 5'-diphosphocholine), citrulline (an a-amino acid), and glutathione (GSH), in varying concentrations.

[00233] In one or more embodiments, the composition comprises at least the active ingredients citicoline, citrulline, and glutathione, and one or more additional active ingredients selected from the group consisting of lipophilic nutrients and vitamins, in varying concentrations.

[00234] In one or more embodiments, the lipophilic nutrient is selected from the group consisting of lutein, zeaxanthin, astaxanthin, beta-carotene, lycopene, Vitamin A, Vitamin D, Vitamin E, Vitamin K, Coenzyme Q10, linoleic acid, alpha linolenic acid, arachidonic acid, docosahexaenoic acid, eicosapentaenoic acid, and combinations thereof.

[00235] In one or more embodiments, the lipophilic nutrient is lycopene. Lycopene is a natural pigment found in ripe fruit, particularly in tomato, or synthesized, especially from a fungus, Blakeslea trispora. It belongs to the carotenoid family and its structure is similar to that of .beta. -carotene. The lycopene content, in a food supplement in accordance with the invention, may be between 0.1% and 30% by weight, especially between 0.1% and 20% by weight, and particularly between 0.1% and 10% by weight, relative to the total weight of the combination of active agents. In one or more embodiments, the lycopene is provided in a range selected from: 5 to 90 mg; 10 to 85 mg; 15 to 80 mg; 20 to 80 mg; 20 to 70 mg; or 20 to 40 mg.

[00236] The lycopene content, in a synergistic composition intended for oral administration or in a food supplement in accordance with the invention, may be between 0.1% and 30% by weight, especially between 0.1% and 20% by weight, and particularly between 0.1% and 10% by weight, relative to the total weight of the combination of active agents. The lycopene content in a cosmetic composition intended for oral administration or in a food supplement in accordance with the invention may be such that the daily dose of said lycopene is between 0.1 and 20 mg/day and especially between 0.5 and 10 mg/day.

[00237] In another embodiment, the composition comprises at least the active ingredients citicoline, citrulline, glutathione, and lycopene, in varying concentrations. [00238] In another embodiment, the composition further comprises a source of carbohydrate. The compositions may comprise from about 5% to about 90% carbohydrate. In another embodiment, the compositions may comprise from about 30% to about 50% carbohydrate. In another embodiment, the compositions may comprise from about 30-40g carbohydrate.

[00239] Examples of such carbohydrates include grains or cereals such as rice, corn, milo, sorghum, alfalfa, barley, soybeans, canola, oats, wheat, and mixtures thereof. The compositions may also optionally comprise other materials such as dried whey and other dairy by-products. In another embodiment, the carbohydrates are selected from the group consisting of complex carbohydrates such as potato starch.

[00240] Health and Medical Formulations For Neurodegenerative Disease Or Condition

[00241] Some embodiments of the present disclosure provide for methods and compositions for improved memory and the treatment of dementia and other neurodegenerative diseases or conditions. Some embodiments of the present disclosure provide for methods and compositions for improved cognitive abilities in subjects with memory loss, cognitive decline or dementia.

[00242] In some embodiments, there is provided a combination composition such as described before for its use in preventing, inhibiting, retarding or treating neuronal degeneration in a subject suffering from a neurodegenerative disease or condition. In one or more embodiments, the neurodegenerative disease is multiple sclerosis, vascular dementia, Parkinson's disease, or Alzheimer's disease.

[00243] In some embodiments, the present invention provides a beverage formulation comprising a pharmaceutical composition containing a therapeutically effective amount of the synergistic composition for preventing, inhibiting, retarding or treating neuronal degeneration in a subject suffering from a neurodegenerative disease or condition; a beverage component; and a diluent.

[00244] More particularly the invention provides a combination composition for its use in preventing inhibiting, retarding or treating a subject suffering from a disease or condition selected from the group consisting of: Alzheimer's disease (AD), senile dementia of AD type (SDAT), Parkinson's disease, Lewis body dementia, vascular dementia, autism, myasthenia gravis, Lambert Eaton disease, mild cognitive impairment (MCI), age-associated memory impairment (AAMI) and problem associated with ageing, (i) non-cognitive neurodegeneration, (ii) non-cognitive neuromuscular degeneration, (iii) motor-sensory neurodegeneration, or (iv) receptor dysfunction or loss in the absence of cognitive, neural and neuromuscular impairment, in a human or non-human animal subject suffering from, or susceptible to, any of Parkinson's disease, postencephalitic Parkinsonism, depression, schizophrenia, muscular dystrophy including facioscapulohumeral muscular dystrophy (FSH), Duchenne muscular dystrophy, Becker muscular dystrophy and Bruce's muscular dystrophy, Fuchs' dystrophy, myotonic dystrophy, corneal dystrophy, reflex sympathetic dystrophy syndrome (RSDSA), neurovascular dystrophy, Huntington's disease, motor neurone diseases including amyotrophic lateral sclerosis (ALS), multiple sclerosis, postural hypotension, traumatic neurodegeneration, Batten's disease, Cockayne syndrome, Down syndrome, corticobasal ganglionic degeneration, multiple system atrophy, cerebral atrophy, olivopontocerebellar atrophy, dentatorubral atrophy, pallidoluysian atrophy, spinobulbar atrophy, optic neuritis, subacute sclerosing panencephalitis (SSPE), attention deficit disorder, post-viral encephalitis, post-poliomyelitis syndrome, Fahr's syndrome, Joubert syndrome, Guillain-Barre syndrome, lissencephaly, Moyamoya disease, neuronal migration disorders, autistic syndrome, polyglutamine disease, Niemann-Pick disease, progressive multifocal leukoencephalopathy, pseudotumor cerebri, Refsum disease, Zellweger syndrome, supranuclear palsy, Friedreich's ataxia, spinocerebellar ataxia type 2, Rhett syndrome, Shy-Drager syndrome, tuberous sclerosis, Pick's disease, chronic fatigue syndrome, neuropathies including hereditary neuropathy, diabetic neuropathy and anti-mitotic neuropathy, prion-based neurodegeneration, including Creutzfeldt-Jakob disease (OD), variant CJD, new variant CJD, bovine spongiform encephalopathy (BSE), GSS, FFI, kuru and Alper's syndrome, Joseph's disease, acute disseminated encephalomyelitis, arachnoiditis, vascular lesions of the central nervous system, loss of extremity neuronal function, Charcot-Marie-Tooth disease, susceptibility to heart failure, asthma, and macular degeneration. The composition is particularly useful for the treatment and prevention of Alzheimer disease.

[00245] According to still another object of the present invention, there is provided a method for preventing, inhibiting, retarding or treating neuronal degeneration in a subject in need thereof, wherein the method comprises administering an effective amount of the composition according to the invention to said subject.

[00246] As described herein, the combination compositions according to the present invention may be prepared as pharmaceutical compositions, especially pharmaceutical compositions useful for the treatment of dementia and Alzheimer's disease. Such compositions may comprise the active compounds (i) and (ii) as defined above together with a pharmaceutically acceptable excipient. Some embodiments of the present disclosure can be consumed daily for its preventive health benefits or as needed before or after activity. [00247] In one or more embodiments, the synergistic composition comprises at least the active ingredients N-acetylcysteine amide (NAC amide or NACA), an anthocyanin or anthocyanidin, astaxanthin, catachins or epicatechins, a choline, 1-citrulline, curcumin or curcuminoid, ergothioneine, glutathione, phosphatidylserine, yamabushitake, or salt thereof in varying concentrations.

[00248] In one or more embodiments, the synergistic composition comprises at least the active ingredients N-acetylcysteine amide (NAC amide or NACA), an anthocyanin or anthocyanidin, astaxanthin, catachins or epicatechins, citicboline, 1-citrulline, curcumin or curcuminoid, ergothioneine, glutathione, phosphatidylserine, yamabushitake, or salt thereof in varying concentrations.

[00249] In one or more embodiments, the synergistic composition comprises at least the active ingredients N-acetylcysteine amide (NAC amide or NACA), an anthocyanin or anthocyanidin, astaxanthin, bacopa monnieri extract, catechins or epicatechins, chlorogenic acid, citicholine, 1-citrulline, curcumin or curcuminoid, ergothioneine, fisetin, glutathione, huperzine A, phosphatidylserine, Rhodiola rosea extract, yamabushitake, or salt thereof in varying concentrations.

[00250] In one or more embodiments, the synergistic composition comprises at least the active ingredients N-acetylcysteine amide (NAC amide or NACA), astaxanthin, bacopa monnieri extract, green tea extract, chlorogenic acid, citicholine, 1-citrulline, curcumin, cyanidin-3-glucoside (Cy-g), ergothioneine, fisetin, glutathione, huperzine A, phosphatidylserine, Rhodiola rosea extract, yamabushitake, or salt thereof in varying concentrations.

[00251] In one or more embodiments, the synergistic composition for preventing, inhibiting, retarding or treating neuronal degeneration in a subject in need thereof comprises at least the active ingredients N-acetylcysteine amide (NAC amide or NACA), bacopa monnieri extract, chlorogenic acid, citicoline (also known as CDP-cho!ine or eytidine 5'-diphosphocho!ine), 1- citrulline, cyanidin 3,5 diglucoside, curcumin, ergothioneine, fisetin, glutathione, green tea extract or catachins, huperzine A, phosphatidylserine, Rhodiola rosea extract, yamabushitake, or salt thereof in varying concentrations.

[00252] In one or more embodiments, the synergistic composition for preventing, inhibiting, retarding or treating neuronal degeneration in a subject in need thereof comprises at least the active ingredients N-acetylcysteine amide (NAC amide or NACA), cyanidin-3-glucoside (Cy- g) or cyanidin-3,5-diglucoside (Cy-dg), bacopa monnieri extract, chlorogenic acid, citicoline

(also known as CDP-choline or eytidine S'-diphosphocholine), citrulline, curcumin, ergothioneine, fisetin, glutathione, green tea extract or catachins, huperzine A, phosphatidylserine, Rhodiola rosea extract, yamabushitake, or salt thereof in varying concentrations.

[00253] In one or more embodiments, the synergistic composition for preventing, inhibiting, retarding or treating neuronal degeneration in a subject in need thereof comprises at least the active ingredients N-acetylcysteine amide (NAC amide or NACA), cyanidin-3-glucoside (Cy- g) and/or cyanidin-3,5-diglucoside (Cy-dg), bacopa monnieri extract, chlorogenic acid, citicoline (also known as CDP-choime or cytidine S'-diphosphocholme), 1-citrulline or 1- citrulline malate DL 2: 1, curcumin, ergothioneine, fisetin, glutathione, green tea extract or catachins, huperzine A, phosphatidylserine, Rhodiola rosea extract, yamabushitake, or salt thereof in varying concentrations.

[00254] In one or more embodiments, the synergistic composition comprises at least the active ingredients N-acetylcysteine amide (NAC amide or NACA), bacopa monnieri extract, catechins or epicatechins, chlorogenic acid, citicholine, 1-citrulline, curcumin or curcuminoid, ergothioneine, glutathione, huperzine A, phosphatidylserine, Rhodiola rosea extract, yamabushitake, or salt thereof in varying concentrations.

[00255] In another embodiment, the synergistic composition comprises at least the active ingredients from about 300 to about 500 mg N-acetylcysteine amide, from about 100 to about 400 mg bacopa monnieri extract, from about 400 to about 700 mg green tea extract (95% polyphenols; 45% EGCG), from about 100 to about 300 mg chlorogenic acid, from about 300 to about 700 mg citicholine, from about 2 to about 6 g 1-citrulline, from about 50 mg to about 300 mg lipidated curcumin, from about 10 to about 100 mg ergothioneine, from about 300 to about 700 mg glutathione, from about 10 to about 300 mg huperzine A, from about 50 to about 300 mg olive leaf extract; from about 100 to about 300 mg phosphatidylserine, from about 100 to about 500 mg Rhodiola rosea extract (3-5% rosavins and 2-4% salidroside), from about 100 to about 300 mg yamabushitake (95%), or salt thereof in varying concentrations.

[00256] In another embodiment, the synergistic composition comprises at least the active ingredients from about 350 to about 450 mg N-acetylcysteine amide, from about 200 to about 300 mg bacopa monnieri extract, from about 450 to about 600 mg green tea extract (95% polyphenols; 45% EGCG), from about 100 to about 200 mg chlorogenic acid, from about 400 to about 600 mg citicholine, from about 3 to about 5 g 1-citrulline, from about 100 mg to about 200 mg lipidated curcumin, from about 25 to about 50 mg ergothioneine, from about 400 to about 600 mg glutathione, from about 50 to about 200 mg huperzine A, from about 50 to about 200 mg olive leaf extract; from about 100 to about 200 mg phosphatidylserine, from about 100 to about 300 mg Rhodiola rosea extract (3-5% rosavins and 2-4% salidroside), from about 200 to about 200 mg yamabushitake (95%), or salt thereof in varying concentrations.

[00257] In one specific example, the formulation includes olive leaf extract standardized to contain from about 1% to about 25% oleuropein. In anotehr example, the olive leaf extract contains about 18-22% oleuropein. In a specific example, the olive leaf extract contains about 20% oleuropein. In another embodiment, the composition comprises a therapeutically effective amount of a water-based extract derived from olive (Olea europaea) leaves, wherein the compounds oleuropein and hydroxytyrosol are present in the extract at a ratio of approximately 0.5 to 2.0 parts hydroxytyrosol to approximately 5 parts oleuropein.

[00258] In one or more embodiments, the composition further comprises one or more additional agents selected from the group comprising brown algae, cyanidin 3 glucoside (cy- g), cyanidin 3,5 diglucoside (cy-dg), 7,8-dihydroxyflavone (7,8-DHF), ferulic acid, muira puama , oxiracetam, Rhodiola crenulata extract, and quercetin, in varying concentrations.

[00259] In one or more embodiments, the composition further comprises brown algae, cyanidin 3 glucoside (cy-g), cyanidin 3,5 diglucoside (cy-dg), 7,8-dihydroxyflavone (7,8- DHF), ferulic acid, muira puama , oxiracetam, Rhodiola crenulata extract, and quercetin, in varying concentrations.

[00260] In one or more embodiments, the composition further comprises brown algae, cyanidin 3 glucoside (cy-g), cyanidin 3,5 diglucoside (cy-dg), 7,8-dihydroxyflavone (7,8- DHF), ferulic acid, muira puama , oxiracetam, Rhodiola crenulata extract, and quercetin, in varying concentrations.

[00261] In one or more embodiments, the composition further comprises one or more additional agents selected from the group comprising bacopa monnieri extract, brown algae, chlorogenic acid, cyani din-3 -glucoside (Cy-g), cyanidin-3,5-diglucoside (Cy-dg), 7,8- dihydroxyflavone (7,8-DHF), ferulic acid, huperzine A, krill oil, muira puama , oxiracetam, Rhodiola Crenulata Extract, Rhodiola Rosea Extract, quercetin

[00262] In one or more embodiments, the active ingredient N-acetylcysteine amide (NAC amide or NACA) of the composition comprises N-acetylcysteine amide (NAC amide or NACA) or derivatives thereof, or a physiologically acceptable derivative, salt, or ester thereof, glutathione N-acetylcysteine amide (NAC amide), or a physiologically or pharmaceutically acceptable derivative or salt or ester thereof, for use in a variety of disorders, conditions, pathologies and diseases in which oxidative stress and/or free radical formation cause damage, frequently systemic damage, to cells, tissues and organs of the body. The invention encompasses a pharmaceutically acceptable composition comprising NAC amide, e.g., water- soluble NAC amide, or physiologically acceptable derivatives, salts, or esters thereof, which can be used in treatment and therapeutic methods in accordance with this invention. In one or more embodiments, the amounts of N-acetylcysteine amide (NAC amide or NACA) or a physiologically acceptable derivative, salt, or ester thereof, used within supplements and compositions of the invention include about 100 mg to about 1500 mg, about 200 mg to about 1400 mg, about 300 mg to about 1300 mg, or about 400 mg to about 1200 mg, or any intervening range therein. In particular preferred embodiments, a supplement or composition comprises at least about 200 mg, about 400 mg, about 600 mg, about 800 mg, about 900 mg, about 1000 mg, about 1100 mg, or about 1200 mg or any intervening amount therein. In one or more embodiments, the anthocyanin or anthocyanidin is present in said formulation in an amount of about 450 to 1200 mg.

[00263] In one or more embodiments, the anthocyanin component may comprise an anthocyaninin-rich extract. In one or more embodiments, the anthocyanin component may comprise cyanidin-3-O-galactoside, cyanidin-3-glucoside (cy-g) or cyanidin-3,5-0- diglucoside (cy-dg).

[00264] The term "anthocyanin" refers to a class of flavonoids, which may be glycosylated (such as cyanidine, malvidine, delphinidine, pelargonidine, peonidine, petunidine) or not glycosylated. The anthocyanins (anthocyanidins with sugar group) are mostly 3-glucosides of the anthocyanidins. The anthocyanins are subdivided into the sugar-free anthocyanidin aglycones and the anthocyanin glycosides.

[00265] In one or more embodiments, the anthocyanin-rich extract comprises at least one of delphini din-3 -galactoside; delphindin-3-glucoside; cyanidin-3-galactoside; delphini din-3 - arabinoside; cyanidin-3-glucoside; petuni din-3 -galactoside; petuni din-3 -glucoside; cyanidin- 3-arabinoside; peoni din-3 -galactoside; peruni din-3 -arabinoside; malvi din-3 -galactoside; peoni din-3 -glucoside; malvi din-3 -glucoside; peoni din-3 -arabinoside; malvi din-3 -arabinoside; delphini din-6-acetyl-3 -glucoside; cyanidin-6-acetyl-3 -glucoside; malvi din-6-acetyl-3- galactoside; petunidin-6-acetyl-3-glucoside; peonidin-6-acetyl-3 -glucoside; and malvidin-6- acetyl-3 -glucoside. According to another embodiment, the anthocyanin-rich extract comprises at least one of delphinidin 3-sambubioside-5-glucoside; delphinidin 3,5-diglucoside; cyanidin 3 -sambubioside-5 -glucoside; cyanidin 3,5-diglucoside; delphinidin 3-sambubioside; delphinidin 3 -glucoside; cyanidin 3-sambubioside; and cyanidin 3 -glucoside.

[00266] According to another embodiment, the therapeutically effective amount of the anthocyanin-rich extract is from about 10 mg/day to about 10 g/day. According to another embodiment, the therapeutically effective amount of the anthocyanin-rich extract is from about 0.01 mg/kg body weight to about 10 g/kg body weight. According to some such embodiments, the therapeutically effective amount of the anthocyanin-rich extract is about 0.5 mg/kg body weight to about 10 g/kg body weight. According to some such embodiments, the therapeutically effective amount of the anthocyanin-rich extract is about 1.5 mg/kg body weight to about 5 g/kg body weight.

[00267] According to some such embodiments, the formulations of flavonoids, anthocyanins, or derivatives or variants thereof, including, but not limited to, the anthocyanins of blueberry such as, for example, delphini din-3 -galactoside; delphindin-3-glucoside; cyanidin-3-galactoside; delphinidin-3-arabinoside; cyanidin-3-glucoside; petunidin-3- galactoside; petuni din-3 -glucoside; cyanidin-3-arabinoside; peoni din-3 -galactoside; peruni din-3 -arabinoside; malvi din-3 -galactoside; peoni din-3 -glucoside; malvi din-3 -glucoside; peoni din-3 -arabinoside; malvi din-3 -arabinoside; delphini din-6-acetyl-3 -glucoside; cyani din- 6-acetyl-3-glucoside; malvidin-6-acetyl-3-galactoside; petuni din-6-acetyl-3 -glucoside; peoni din-6-acetyl-3 -glucoside; malvidin-6-acetyl-3-glucoside (Prior, R, et al. 2001), and the anthocyanins of maqui berries such as, for example, delphini din 3 -sambubioside-5 -glucoside; delphinidin 3,5-diglucoside; cyanidin 3 -sambubioside-5 -glucoside; cyanidin 3,5-diglucoside; delphini din 3-sambubioside; delphinidin 3 -glucoside; cyanidin 3-sambubioside; cyanidin 3- glucoside, may be administered in pharmaceutically acceptable solutions, which routinely may contain pharmaceutically acceptable concentrations of salt, buffering agents, preservatives, compatible carriers, adjuvants, and optionally other therapeutic ingredients.

[00268] For use in therapy, an effective amount of the flavonoid, anthocyanin, or derivative or variant thereof, including, but not limited to, the anthocyanins of blueberry such as, for example, delphini din-3 -galactoside; delphindin-3 -glucoside; cyani din-3 -galactoside; delphini din-3 -arabinoside; cyani din-3 -glucoside; petuni din-3 -galactoside; petuni din-3 - glucoside; cyani din-3 -arabinoside; peoni din-3 -galactoside; peruni din-3 -arabinoside; malvi din- 3 -galactoside; peoni din-3 -glucoside; malvi din-3 -glucoside; peoni din-3 -arabinoside; malvi din- 3 -arabinoside; delphini din-6-acetyl-3 -glucoside; cyani din-6-acetyl-3 -glucoside; malvi din-6- acetyl-3 -galactoside; petuni din-6-acetyl-3 -glucoside; peonidin-6-acetyl-3-glucoside; malvi din-6-acetyl-3 -glucoside (Prior, R, et al. 2001), and the anthocyanins of maqui berries such as, for example, delphinidin 3-sambubioside-5-glucoside; delphinidin 3,5-diglucoside; cyanidin 3 -sambubioside-5 -glucoside; cyanidin 3,5-diglucoside; delphinidin 3-sambubioside; delphinidin 3-glucoside; cyanidin 3-sambubioside; cyanidin 3-glucoside, may be administered to a subject by any mode that delivers the compound to the desired surface. [00269] In a further embodiment, the anthocyanin extract of the invention comprises: at least 10% anthocyanins; at least 30% total polyphenols; and at least 5% cyanidin-3-glucoside. In a further embodiment, the present invention also provides a composition comprising between 50 and 1200 mg anthocyanin extract, more in particular between 50 and 800 mg, even more in particular between 70 and 600 mg, even more in particular between 90 and 300 mg. In a particular embodiment, the composition of the invention is formulated in a daily dosage form comprising at least 3, 6, 12, 20, 30, 40, 50, 60, 70, 80, 90, 100 mg or more of anthocyanins.

[00270] Astaxanthin is a xanthophyll contained in Crustacea such as shrimp, and crab; fish and shellfish such as salmon, sea bream, carp, goldfish, starfish, barnacle, krill, squid, and octopus; plants such as petals of Adonis ramosa; Aves such as chicken; microorganisms such as green algae (Haematococcus pluvialis), Euglena (Euglena heliorubescens), Chlorella (Chlorela zofmgiensis), red yeast (Phaffia rhodozyma), thermophilic bacteria (Meiothermus ruber) and the like. The astaxanthin used in the present invention may be extracted from these natural products, obtained by culturing astaxanthin-producing microorganisms or chemically synthesized.

[00271] In one or more embodiments, the astaxanthin comprises a natural or synthetic ester or synthetic diol derivative. In one or more embodiments, the amounts of astaxanthin used within the presently disclosed supplements and compositions of the invention comprises a daily dose of 0.5-24 mg, 0.5-18 mg, 1-12 mg, 6-12 mg, and other ranges, and up to 24 mg, including 6-12 mg. According to another embodiment, the therapeutically effective amount of the astaxanthin is from about 10 mg/day to about 10 g/day. According to another embodiment, the therapeutically effective amount of the astaxanthin is from about 0.01 mg/kg body weight to about 10 g/kg body weight.

[00272] In one or more embodiments, the amounts of Bacopa monnieri extract [synonym Bacopa monniera; Herpestis monniera; Moniera cuneifolia] used within the presently disclosed supplements and compositions of the invention comprise one or more bacosides. In one or more embodiments, the one or more bacosides preferably selected from the group consisting of bacoside A, bacoside B and mixtures thereof. In one or more embodiments, the amounts of Bacopa monnieri extract used within the presently disclosed supplements and compositions of the invention comprises 100-300 mg of Bacopa monnieri or the equivalent of 6 g of dry herb with a total bacoside content of 55% by weight. In one or more embodiments, the Bacopa monnieri extract or fraction contains total bacosides in the range of 20 to 80% as per spectrometric method of analysis and/or 5 to 55% of total bacosides as per HPLC method of analysis. In one or more embodiments, the Bacopa monnieri extract enriched to contain not less than 55% total bacosides.

[00273] In one or more embodiments, the present method comprises the administration of an effective amount of bacosides, the bacoside being provided by a Bacopa plant material enriched in bacosides. In one or more embodiments, the Bacopa plant material used in the present method comprises at least 1 wt. %, more preferably at least 5 wt. %, even more preferably at least 10 wt. %, even more preferably at least 25 wt. %, most preferably at least 40 wt. % bacosides based on the total dry weight of the Bacopa plant material. In a further embodiment of the present method, bacosides are administered, preferably through the Bacopa plant material, in a daily amount of between 0.1 and 250 mg bacoside per kg of body weight, between 0.5 and 100 mg/kg, between 1 and 75 mg/kg, or between 2 and 50 mg/kg.

[00274] In one or more embodiments, the present method comprises the administration of an effective amount of brown algae. Ascophyllum nodosum or Ascophylle noueuse is a marine algae classed in the family of the Fucaceae. The extract of brown algae Ascophyllum nodosum may be used in this invention and can be prepared by any extraction and purification method known to those skilled in the art. In one or more embodiments, the amounts of brown algae extract used within the presently disclosed supplements and compositions of the invention comprises a daily dose of 0.5-24 mg, 0.5-18 mg, 1-12 mg, 6-12 mg, and other ranges, and up to 24 mg, including 6-12 mg.

[00275] Chlorogenic acid is an ester of caffeic acid and quinic acid. Chlorogenic acid is the major polyphenolic compound in coffee, isolated from the leaves and fruits of dicotyledonous plants. The composition of the invention may be formulated to contain one or more chlorogenic acids. Such chlorogenic acids include, but are not limited to, 3-O-Caffeoylquinic acid (3 CQA), 4-O-Caffeoylquinic acid (4 CQA), 5-O-Caffeoylquinic acid (5 CQA), 5-O-Feruloylquinic acid, 3,4-O-Dicaffeoylquinic acid (3,4 Di CQA), 3,5-O-Dicaffeoylquinic acid (3, 5 Di CQA), 4,5- O-Dicaffeoylquinic acid (4,5 Di CQA), and combinations thereof. The composition may be formulated to attain a particular chlorogenic acid content. The composition may have a total chlorogenic acid content of between about 0.01-6% w/w. The composition may have a total chlorogenic acid content, by weight, of at least 0.01%, 0.025%, 0.05%, 0.1%, 0.15%, 0.25%, 0.5%, 1%, 2%, 3%, 4%, 5%, or more as well as any amount intervening these specifically described amounts.

[00276] In one or more embodiments, the amounts of the one or more chlorogenic acids used within supplements and compositions of the invention include about 25 mg to about 1000 mg, or about 50 mg to about 750 mg, or about 75 mg to about 500 mg, or about 100 mg to about 500 mg, or about 120 mg to about 300 mg, or any intervening range therein. In particular preferred embodiments, a supplement or composition comprises at least about 25 mg, about 50 mg, about 75 mg, about 100 mg, about 120 mg, about 200 mg, about 250 mg, or about 3000 mg or any intervening amount therein. In one or more embodiments, the phosphatidylserine is present in said formulation in an amount of about 120-300 mg.

[00277] In one or more embodiments, the disclosed compositions comprise embodiments wherein a therapeutically effective amount of the cyanidin 3,5-diglucoside per kg body weight per day of about 1 mg/kg, 1.5mg/kg, 2.0 mg/kg, 2.5 mg/kg, 3 mg/kg, 4.0 mg/kg, 5.0 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 25 mg/kg, 30 mg/kg, 35 mg/kg, 40 mg/kg, 45 mg/kg 50 mg/kg, 55 mg/kg, 60 mg/kg, 65 mg/kg, 70 mg/kg, 75 mg/kg, 80 mg/kg, 85 mg/kg, 90 mg/kg, 95 mg/kg, 100 mg/kg, 125 mg/kg, 150 mg/kg, 200 mg/kg, 250 mg/kg, 300 mg/kg, 350 mg/kg, 400 mg/kg, 450 mg/kg, 500 mg/kg, 550 mg/kg, 600 mg/kg, 650 mg/kg, 700 mg/kg, 750 mg/kg, 800 mg/kg, 850 mg/kg, 900 mg/kg, 950 mg/kg, 1 g/kg, 5 g/kg, 10 g/kg, or more.

[00278] In a further embodiment, the present invention also provides a composition comprising between 50 and 1200 mg cyanidin 3,5-diglucoside, more in particular between 50 and 800 mg, even more in particular between 70 and 600 mg, even more in particular between 90 and 300 mg. In a particular embodiment, the composition of the invention is formulated in a daily dosage form comprising at least 3, 6, 12, 20, 30, 40, 50, 60, 70, 80, 90, 100 mg or more of cyanidin 3,5-diglucoside.

[00279] In one or more embodiments, the disclosed compositions comprise embodiments wherein the choline is provided by an ingredient selected from the group consisting of choline chloride, choline bitartrate, citicoline (CDP-choline), L-alpha-glycerophosphocholine (Alpha- GPC), lecithin, phosphatidylcholine, and mixtures thereof. In one or more embodiments, the choline is present in 100-1500 mg, 200-1400 mg, 300-1300 mg, 400-1200 mg, 400-1100 mg, or 400-1000 mg. The composition can be administered to the individual in a daily dose that provides 5.5 mg/day to 5,500 mg/day of the choline.

[00280] In one or more embodiments, the disclosed compositions comprise embodiments wherein citicoline (also known as cytidine diphosphate-choline, CDP-choline or cytidine 5'- diphosphochofine) is present in 100-1500 mg, 200-1400 mg, 300-1300 mg, 400-1200 mg, 400- 1100 mg, or 400-1000 mg.

[00281] In one or more embodiments, the disclosed synergistic compositions comprise embodiments wherein citrulline is present in 2-10 g, 4-9g, 5-9 g, 6-8 g, or 8 g. Citrulline is an alpha-amino acid, and can be any bioavailable form of citrulline, including, for example, citrulline malate. In one or more embodiments, the disclosed compositions comprise embodiments wherein citrulline is present as L-citrulline DL-malate 2: 1, which combines two- parts L-citrulline with one-part DL-malic acid, wherein citrulline is present in 2-10 g, 4-9g, 5- 9 g, 6-8 g, or 8 g.

[00282] Citrulline can be present as the active substance (ii) in a combination product of the present invention in a more or less purified form, especially in the form of a plant extract. It can also come in a free form or as derivatives. Citrulline derivatives that are acceptable according to the present invention especially include complex forms, protected forms (like esterified forms and forms wherein the amine function is protected by the tert-butoxy carbonyl group, i.e. Boc) or salts, as well as precursors thereof, like ornithine or glutamine. As an example, a combination product of the invention may include, as an active substance (ii), at least one substance selected from the group consisting of: D, L-citrulline, L-citrulline, D,L- citrulline malate, L-citrulline malate, L-citrulline monoacetate, L-citrulline hydrochloride, L- citrulline methylester, L-citrulline ethylester, L-citrulline-n-hexylester, L-citrulline (benzoylmethyl)ester, alpha-N-benzoyl -L-citrulline methylester, B-Boc-citrulline, Nl-2,4- dinitrophenyl-D, L-citrulline and their mixtures in whatever proportions. Citrulline may come in a purified form or as a plant extract containing the same, especially as a plant extract belonging to the cucurbitaceae plant family.

[00283] In one example, a supplement formulation can include citrulline at from about 1 wt % to about 45 wt %. In other examples, supplement formulations can include citrulline at from about 10 wt % to about 20 wt %, at from about 5 wt % to about 20 wt %, at from about 10 wt % to about 25 wt %, at from about 10 wt % to about 30 wt %, at from about 5 wt % to about 25 wt %, at from about 10 wt % to about 30 wt %, or at from about 5 wt % to about 15 wt %.

[00284] As disclosed herein the term "curcuminoid" or "curcuminoid mixture" is a mixture of curcumin, demethoxycurcumin and bisdemethoxycurcumin. In some embodiments, curcumin is the major component of the curcuminoid mixture. In some embodiments, demethoxycurcumin is a minor component of the curcuminoid mixture. In some embodiments, bisdemethoxycurcumin is a minor component of the curcuminoid mixture. In some embodiments, 95% of the crystals having curcuminoid mixture are composed of curcumin, demethoxycurcumin and bisdemethoxycurcumin.

[00285] In certain embodiments, the curcuminoid is selected from a group consisting of curcumin, desmethoxycurcumin, bis-desm ethoxy curcumin, tetrahydrocurcuminoid, curcuminglucuronide, curcumin sulfate, hexahydrocurcumin or combinations thereof. The curcuminoid in the composition is preferably curcumin or a mixture of curcuminoids containing curcumin. Curcuminoids include as curcumin as well as demethoxycurcumin and bisdem ethoxy curcumin and their geomentrical isomers and metabolites. In certain embodiments, a curcuminoid is curcumin.

[00286] In some cases, a dietary supplement composition can contain one or more than one curcuminoid. A dietary supplement composition can contain any appropriate amount of a curcuminoid. For example, at least 3 percent (e.g., at least 5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 70, 80, or 90 percent) of a dietary supplement composition provided herein can be a curcuminoid. In some cases, a dietary supplement composition provided herein can contain between about 10 mg and about 5000 mg (e.g., between about 250 mg and about 5000 mg, between about 500 mg and about 5000 mg, between about 1000 mg and about 5000 mg, between about 1000 mg and about 4000 mg, between about 1000 mg and about 3000 mg, between about 1000 mg and about 2000 mg) of a curcuminoid.

[00287] The curcumin or curcuminoid mixture, suitable for use in supplements and compositions of the invention may be supplied in natural and synthetic forms. In one or more embodiments, the amounts of curcumin or curcuminoid mixture used within supplements and compositions of the invention include about 0.5 g to about 6 g, about 1 g to about 5g, about 2 g to about 5 g or about 3 g to about 4 g or any intervening range therein. In particular preferred embodiments, a supplement or composition comprises at least about 1 g, about 2 g, about 3 g, about 3.5 g, 4 g, about 4.5 g, or about 5 g or any intervening amount therein of curcumin or curcuminoid mixture. In one or more embodiments, the curcumin or curcuminoid mixture is present in said formulation in an amount of about 3-4g.

[00288] Some embodiments provide a composition for enhanced bioavailability of curcumin. The composition includes a curcuminoid mixture and essential oil of turmeric. The curcuminoid mixture includes curcumin, demethoxycurcumin and bisdemethoxycurcumin. The essential oil of turmeric ranges from about 20% ar-turmerone to about 60% ar-turmerone. The weight ratio of the curcuminoid mixture to essential oil of turmeric ranges from about 1 :3 to about 99: 1.

[00289] Suitable curcumin type compound can be either pure curcumin (diferuloylmethane) or curcuminoid mixture (e.g. that extracted from turmeric, contains approximately 70-80% diferuloylmethane, 10-20% demethoxycurcumin, and 5-10% bisdemethoxycurcumin) or curcumin derivatives. The pure curcumin (diferuloylmethane) performs similar as curcuminoid extracted from turmeric. The terms curcumin, turmeric extract and curcuminoid are used interchangeable in the current invention. [00290] The composition of the invention may be formulated to contain a therapeutically effective amount of 7,8-dihydroxyflavone (7,8-DHF) or pharmaceutically acceptable salts, prodrugs, and derivatives thereof. The composition may have a total 7,8-dihydroxyflavone content of between about 0.01-6% w/w. The composition may have a total chlorogenic acid content, by weight, of at least 0.01%, 0.025%, 0.05%, 0.1%, 0.15%, 0.25%, 0.5%, 1%, 2%, 3%, 4%, 5%, or more as well as any amount intervening these specifically described amounts. In one or more embodiments, the amounts of the 7,8-dihydroxyflavone (7,8-DHF) or pharmaceutically acceptable salts, prodrugs, and derivatives thereof used within supplements and compositions of the invention include about 25 mg to about 1000 mg, or about 50 mg to about 750 mg, or about 75 mg to about 500 mg, or about 100 mg to about 400 mg, or about 100 mg to about 300 mg, or any intervening range therein. In particular preferred embodiments, a supplement or composition comprises at least about 25 mg, about 50 mg, about 75 mg, about 100 mg, about 120 mg, about 200 mg, about 250 mg, or about 3000 mg or any intervening amount therein. In one or more embodiments, the phosphatidylserine is present in said formulation in an amount of about 100-200 mg.

[00291] As used herein the term Ergothioneine shall be interpreted to include variants, homologs, optical isomers and the like which retain the antioxidant activity of Ergothioneine or L-Ergothioneine as demonstrated and described herein. Ergothioneine is a naturally- occurring amino acid. Ergothioneine is a natural antioxidant but is unable to be made in human cells, rather it is absorbed from the diet. Ergothioneine from any suitable source may be used according to the invention. L-Ergothioneine is available commercially from Oxis International, Inc., Sigma Chemical, etc. or from dietary sources such as mushrooms and the various sources disclosed herein according to the invention. The compound is also available from Actinobacteria, filamentous fungi, cyanobacteria, Spirulina, oats, barley and other whole food sources. Ergothioneine for use in compositions according to the invention may be obtained from an independent bionutrient source, such as Vitamin D enriched mushrooms disclosed herein, whole food sources, cyanobacteria and Spirulina as disclosed according to the embodiments of the invention.

[00292] Any type of mushroom, mushroom part, component, fungi or even used substrate for cultivating mushrooms, with ergosterol present may be used. This includes all filamentous fungi where ergosterol has been shown to be present and includes the use of tissues such as the mycelia, spores or vegetative cells. This includes, but is not limited to, for example, Coprinus, Agrocybe, Hypholoma, Hypsizygus, Pholiota, Pleurotus, Stropharia, Ganoderma, Grifola, Trametes, Hericium, Tramella, Psilocybe, Agaricus, including for example Agaricus bisporus (e.g. white button mushrooms), Phytophthora achlya, Flammulina, Melanoleuca, Agrocybe, Morchella, Mastigomycotina, Auricularia, Gymnopilus, Mycena, Boletus, Gyromitra, Pholiota, Calvatia, Kuegneromyces, Phylacteria, Cantharellus, Lactarius, Pleurotus, Clitocybe, Lentinula (Lentinus), Stropharia, Coprinus, Lepiota, Tuber, Tremella, Drosophia, Leucocoprinus, Tricholoma, Dryphila, Marasmius, and Volvariella. Non-limiting examples of other fungal genera, including fermentable fungi, include: Altemaria, Endothia, Neurospora, Aspergillus, Fusarium, Penicillium, Blakeslea, Monascus, Rhizopus, Cephalosporium, Mucor, and Trichoderma.

[00293] An embodiment of the present invention also provides natural bionutrients, medical foods and/or beverages comprising combinations of Ergothioneine-enriched mushrooms of the invention including extracts, fractions thereof or compounds thereof or any combination thereof, phytonutrients and/or antioxidants. The food compositions according to the invention may comprise enriched mushrooms from a variety of fungi sources as disclosed according to embodiments herein this description. Alternatively, the food compositions according to the invention may comprise Ergothioneine obtained directly from whole food sources, Spirulina or cyanobacteria. In some embodiments, the ergothioneine is L-ergothioneine. As used herein, the term L-ergothioneine shall also include thiotaine or thiotain.

[00294] In the preparation provided in the present invention, the content of ergothioneine or a pharmaceutically acceptable salt or ester thereof may be in a wide range; for example, the content of ergothioneine may be 0.0005-50 wt %, preferably 0.001-20 wt %, based on the total weight of the preparation. In some embodiments, the amount of ergothioneine or a pharmaceutically acceptable salt or ester thereof is 0.0001-10.0 wt. %, 0.001-10.0 wt. %, 0.01- 10.0 wt. %, 0.1-10.0 wt. %, 1.0-10.0 wt. %, 2.0-8.0 wt. % or 4.0-6.0 wt. % based on the total weight of the formulation of which it is a part.

[00295] The ergothioneine or a pharmaceutically acceptable salt or ester thereof, suitable for use in supplements and compositions of the invention may be supplied in natural and synthetic forms. In one or more embodiments, the amounts of ergothioneine or a pharmaceutically acceptable salt or ester thereof used within supplements and compositions of the invention include about 0.5 g to about 6 g, about 1 g to about 5g, about 2 g to about 5 g or about 3 g to about 5 g or any intervening range therein. In particular preferred embodiments, a supplement or composition comprises at least about 1 g, about 2 g, about 3 g, about 3.5 g, 4 g, about 4.5 g, or about 5 g or any intervening amount therein of ergothioneine or a pharmaceutically acceptable salt or ester thereof. In one or more embodiments, the ergothioneine or a pharmaceutically acceptable salt or ester thereof is present in said formulation in an amount of about 4-6 g.

[00296] In one or more embodiments, the disclosed compositions comprise embodiments wherein ergothioneine or a pharmaceutically acceptable salt or ester thereof is present in a therapeutically effective amount of about 2-5,000 mg, 250-2,500 mg, 500-2,000 mg or 500 mg- 1,000 mg. In one or more embodiments, the disclosed compositions comprise embodiments wherein ergothioneine or a pharmaceutically acceptable salt or ester thereof is administered in a therapeutically effective amount per kg body weight per day of about 1 mg/kg, 1 5mg/kg, 2.0 mg/kg, 2.5 mg/kg, 3 mg/kg, 4.0 mg/kg, 5.0 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 25 mg/kg, 30 mg/kg, 35 mg/kg, 40 mg/kg, 45 mg/kg 50 mg/kg, 55 mg/kg, 60 mg/kg, 65 mg/kg, 70 mg/kg, 75 mg/kg, 80 mg/kg, 85 mg/kg, 90 mg/kg, 95 mg/kg, 100 mg/kg, 125 mg/kg, 150 mg/kg, 200 mg/kg, 250 mg/kg, 300 mg/kg, 350 mg/kg, 400 mg/kg, 450 mg/kg, 500 mg/kg, 550 mg/kg, 600 mg/kg, 650 mg/kg, 700 mg/kg, 750 mg/kg, 800 mg/kg, 850 mg/kg, 900 mg/kg, 950 mg/kg, 1 g/kg, 5 g/kg, 10 g/kg, or more.

[00297] Ferulic acid (FA), also named as 4-hydroxy-3-m ethoxy cinnamic acid, is a phenol acid widely found in a variety of plants. Ferulic acid has a wide range of pharmacological effects such as anti-inflammatory effect, antibacterial effect, antioxidant effect and antitumor effect. In one or more embodiments, the disclosed compositions comprise ferulic acid and derivatives thereof (esters, salts, etc.). In one or more embodiments, the ferulic acid may be made of esters of ferulic acid and of C1-C30 alcohols, in particular methyl ferulate, ethyl ferulate, isopropyl ferulate, octyl ferulate and oryzanyl ferulate. In one or more embodiments, the disclosed compositions comprise embodiments wherein ferulic acid or a pharmaceutically acceptable salt or ester thereof is present in a therapeutically effective amount of about 2-5,000 mg, 250-4500 mg, 500-4,000 mg or 500 mg-3,000 mg. In one or more embodiments, the disclosed compositions comprise embodiments wherein ferulic acid or a pharmaceutically acceptable salt or ester thereof is administered in a therapeutically effective amount per kg body weight per day of about 1 mg/kg, 1.5mg/kg, 2.0 mg/kg, 2.5 mg/kg, 3 mg/kg, 4.0 mg/kg, 5.0 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 25 mg/kg, 30 mg/kg, 35 mg/kg, 40 mg/kg, 45 mg/kg 50 mg/kg, 55 mg/kg, 60 mg/kg, 65 mg/kg, 70 mg/kg, 75 mg/kg, 80 mg/kg, 85 mg/kg, 90 mg/kg, 95 mg/kg, 100 mg/kg, 125 mg/kg, 150 mg/kg, 200 mg/kg, 250 mg/kg, 300 mg/kg, 350 mg/kg, 400 mg/kg, 450 mg/kg, 500 mg/kg, 550 mg/kg, 600 mg/kg, 650 mg/kg, 700 mg/kg, 750 mg/kg, 800 mg/kg, 850 mg/kg, 900 mg/kg, 950 mg/kg, 1 g/kg, 5 g/kg, 10 g/kg, or more. [00298] Fisetin (2-(3,4-dihydroxyphenyl)-3, 7-dihydroxy -4H-chromen-4-one or (3,3 ',4', 7- tetrahydroxyflavone) is a yellow flavonoid polyphenol present at very low quantities in many foods, notably strawberries. Like resveratrol, it has been reported as a sirtuin-activating compound.

[00299] The unit dose of the formulation may comprise fisetin or a plant extract containing fisetin in an amount of at least about 10 mg, at least about 50 mg, at least about 100 mg, at least about 250 mg, at least about 300 mg, at least about 400 mg, at least about 500 mg, at least about 1 g, or at least about 2 g.

[00300] Fisetin may be provided by a number of plant sources, including fruits and vegetables, such as strawberries, applies, grapes, milk thistle and onions. Fisetin also may be found in Eudicotyledons such as trees and shrubs in the family Fabaceae, such as the acacias Acacia greggii and Acacia berlandieri, parrot tree the parrot tree (Butea frondosa), the honey locust, Gleditsia triacanthos, members of the family Anacardiaceae, such as the Quebracho Colorado and species of the genus Rhus, which contains the sumacs. Fisetin also may be provided by the yellow cypress (Callitropsis nootkatensis). When either kaempferol or fisetin is combined with other brain nutrients, a synergistic effect may be observed.

[00301] In one or more embodiments, the disclosed compositions comprise embodiments wherein fisetin or a plant extract containing fisetin or a pharmaceutically acceptable salt or ester thereof is present in a therapeutically effective amount of about 2-5,000 mg, 250-2,500 mg, 500-2,000 mg or 500 mg-1,000 mg. In one or more embodiments, the disclosed compositions comprise embodiments wherein fisetin or a plant extract containing fisetin or a pharmaceutically acceptable salt or ester thereof is administered in a therapeutically effective amount per kg body weight per day of about 1 mg/kg, 1.5mg/kg, 2.0 mg/kg, 2.5 mg/kg, 3 mg/kg, 4.0 mg/kg, 5.0 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 25 mg/kg, 30 mg/kg, 35 mg/kg, 40 mg/kg, 45 mg/kg 50 mg/kg, 55 mg/kg, 60 mg/kg, 65 mg/kg, 70 mg/kg, 75 mg/kg, 80 mg/kg, 85 mg/kg, 90 mg/kg, 95 mg/kg, 100 mg/kg, 125 mg/kg, 150 mg/kg, 200 mg/kg, 250 mg/kg, 300 mg/kg, 350 mg/kg, 400 mg/kg, 450 mg/kg, 500 mg/kg, 550 mg/kg, 600 mg/kg, 650 mg/kg, 700 mg/kg, 750 mg/kg, 800 mg/kg, 850 mg/kg, 900 mg/kg, 950 mg/kg, 1 g/kg, 5 g/kg, 10 g/kg, or more.

[00302] In one or more embodiments, the glutathione (L-Glutamyl-L-Cysteinyl-Glycine, Glu-Cys-Gly). The glutathione may be in its reduced form with a free thiol group (GSH) or in its oxidised form with a disulfide bond (GSSG). In one preferred embodiment, the oligopeptide is oxidised glutathione (GSSG). [00303] In one or more embodiments, the disclosed compositions comprise embodiments wherein the glutathione is selected from the group consisting of oxidized L-glutathione, reduced L-glutathione and glutathione.

[00304] In one or more embodiments, the disclosed compositions comprise embodiments wherein glutathione is present in 300-1500 mg, 400-1200 mg, 500-1000 mg or 400-800 mg. . In one or more embodiments, the disclosed compositions comprise embodiments wherein glutathione is present as reduced glutathione and is present in 100 to 1500 mg; 150 to 1400 mg; 200 to 1300 mg; 250 to 1200 mg; 300 to 1100 mg; 400 to 1000 mg; 450 to 1000 mg; or 500 to 1000 mg.

[00305] In one example, the glutathione can comprise from about 4 wt % to about 98 wt % of the composition. In another example, the glutathione can comprise from 10 wt % to 60 wt % of the composition.

[00306] In one or more embodiments, the disclosed compositions comprise embodiments wherein the citrulline is present in a 1 :5 to 20: 1 ratio, 2.5: 1 to 15: 1 ratio, 5: 1 to 15: 1 ratio, 8: 1 to about 12: 1 ratio, 9: 1 to about 11 : 1 ratio or 10: 1 ratio with the glutathione.

[00307] The four types of catechins (or epicatechins) found in green tea (from Camellia sinensis ) are the epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin gallate (ECG), and epicatechin (EC). EGCG accounts for about 50-80% of the catechins in green tea. Catechins may also be found from other sources such as cocoa.

[00308] In one or more embodiments, the composition comprises an extract from Camellia sinensis or a green tea containing a catechin selected from the group consisting of epigallocatechin gallate, epigallocatechin, epicatechin gallate, epicatechin and combinations thereof, in varying concentrations.

[00309] The catechin can be, but is not limited to, catechin monomers (e.g., flavan-3-ol monomers), catechin isomers, and combinations thereof. Some embodiments comprise catechin esters, such as catechin gallate (CG), gallocatechin (GC), gallocatechin gallate (GCG), epicatechin (EC), epicatechin gallate (ECG), epigallocatechin (EGC), and epigallocatechin gallate (EGCG), and combinations of two or more thereof.

[00310] Some embodiments comprise a plant extract that comprises catechins. In some embodiments, the plant extract comprises more than about 70% (w/w) catechins, more than about 80% (w/w) catechins, more than about 90% (w/w) catechins, or more than about 95% (w/w) catechins. In some embodiments, the plant extract comprises more than 70% (w/w) catechins, more than 80% (w/w) catechins, more than 90% (w/w) catechins, or more than 95% (w/w) catechins. [00311] In some embodiments, the plant extract is a green tea extract. The extract can be of any suitable green tea variety, such as sencha, fukushami sencha, gyokuro, kabusecha, matcha, tencha, genmaicha, hojicha, shincha, ichibancha, nibancha, or sanbancha.

[00312] In some embodiments, the composition comprises from about 250 mg to about 1,500 mg green tea extract comprising at least 20, 30, 40, 50, 60, 70, 80, or 90% (w/w) catechins.

[00313] In one or more embodiments, the composition comprises as an active ingredient a green tea extract containing (-)-gallocatechin gallate (GCG) at 5 to 25% by weight based on a total weight of the composition or the extract and (-)-epigallocatechin gallate (EGCG) at 7 to 15% by weight based on the total weight of the composition or the extract.

[00314] In one or more embodiments, the amounts of catechins or epicatechins or a physiologically acceptable derivative, salt, or ester thereof, used within supplements and compositions of the invention include about 100 mg to about 1500 mg, about 200 mg to about 1400 mg, about 300 mg to about 1000 mg, or about 400 mg to about 800 mg, or any intervening range therein. In particular preferred embodiments, a supplement or composition comprises at least about 200 mg, about 300 mg, about 400 mg, about 500 mg, or about 600 mg or any intervening amount therein. In one or more embodiments, the anthocyanin or anthocyanidin is present in said formulation in an amount of about 500-600 mg.

[00315] Huperzine A ("huperzine") is an alkaloid derived from the club moss Huperzia serrata. The unit dose of the formulation may comprise huperzine A or pharmaceutically acceptable salts, hydrates, polymorphs, or solvates thereof in an amount of at least about 10 pg, 20 pg, 30 pg, 40 pg, 50 pg, 60 pg, 70 pg, 80 pg, 90 pg, 100 pg, or more. In one or more embodiments, the disclosed compositions comprise embodiments wherein huperzine A or pharmaceutically acceptable salts, hydrates, polymorphs, or solvates thereof is present in a therapeutically effective amount of about 50 pg to 400 pg, about 75 pg to 300 pg, about 100 pg to 200 pg„ In one or more embodiments, the disclosed compositions comprise embodiments wherein huperzine A or pharmaceutically acceptable salts, hydrates, polymorphs, or solvates thereof is present in a therapeutically effective amount of about 0.01 mg and about 10 mg, 0.05 mg and about 9 mg, 0.1 mg and about 8 mg, 0.2 mg and about 8 mg, or 0.5 mg and about 8 mg. In one or more embodiments, the disclosed compositions comprise embodiments wherein huperzine A or pharmaceutically acceptable salts, hydrates, polymorphs, or solvates thereof is present in a therapeutically effective amount of about 0.5 mg and about 300 mg, 1 mg and about 200 mg, 10 mg and about 200 mg, 20 mg and about 200 mg, or 50 mg and about 200 mg. Huperzine A can be obtained from Novel Ingredients Services (Los Angeles, Calif.; Catalog No. 018302.1). [00316] In one or more embodiments, the krill oil is derived from Euphasia spp., comprising Eicosapentaenoic (EPA) and Docosahexaenoic (DHA) fatty acids in the form of triacylglycerides and phospholipids. The krill oil includes at least 10% EPA and 5% DHA, of which greater than 50% are in the form of phospholipids and 1-4000 mg of krill oil per daily dose is delivered. In one or more embodiments, the composition includes krill oil supplemented with 0.1-24 mg astaxanthin per daily dose.

[00317] Muira puama is a bush native to the Brazilian Amazon rain forest. Its bark and roots have been used traditionally for a variety of medicinal purposes. In some embodiments of the present disclosure, the composition as disclosed above includes Muira Puama extract in an amount of about 1000 mg to about 1500 milligrams (mg). In one or more embodiments, the disclosed compositions comprise embodiments wherein Muira Puama extract is present in a therapeutically effective amount of about 2-5,000 mg, 250-2,500 mg, 500-2,000 mg or 500 mg- 1,000 mg. In one or more embodiments, the disclosed compositions comprise embodiments wherein Muira Puama extract is administered in a therapeutically effective amount per kg body weight per day of about 1 mg/kg, 1.5mg/kg, 2.0 mg/kg, 2.5 mg/kg, 3 mg/kg, 4.0 mg/kg, 5.0 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 25 mg/kg, 30 mg/kg, 35 mg/kg, 40 mg/kg, 45 mg/kg 50 mg/kg, 55 mg/kg, 60 mg/kg, 65 mg/kg, 70 mg/kg, 75 mg/kg, 80 mg/kg, 85 mg/kg, 90 mg/kg, 95 mg/kg, 100 mg/kg, 125 mg/kg, 150 mg/kg, 200 mg/kg, 250 mg/kg, 300 mg/kg, 350 mg/kg, 400 mg/kg, 450 mg/kg, 500 mg/kg, 550 mg/kg, 600 mg/kg, 650 mg/kg, 700 mg/kg, 750 mg/kg, 800 mg/kg, 850 mg/kg, 900 mg/kg, 950 mg/kg, 1 g/kg, 5 g/kg, 10 g/kg, or more. In one or more embodiments, the total daily dosage of Muira puama in the nutraceutical composition of the present invention is about 100 mg to about 3 g. In another embodiment, the total daily dosage of Muira puama in the nutraceutical composition of the present invention is about 500 mg to about 1.5 g.

[00318] In some embodiments of the present disclosure, the composition as disclosed above includes a racetam selected from levetiracetam, piracetam, pramiracetam, aniracetam, or. In some embodiments of the present disclosure, the racetam is oxiracetam. In some embodiments of the oxiracetam is L-oxiracetam. The dosage of oral formulations of L-oxiracetam described above is 5-30 mg/kg/day, more preferably 10-20 mg/kg/day. The dosage of injection of L- oxiracetam is 50-90 mg/kg/times. The dosage of oral formulations of L-oxiracetam described above is 10-60 mg/kg/day, and more preferably is 20-40 mg/kg/day. The dosage of injection of oxiracetam is 50-90 mg/kg/times.100-180 mg/kg/times. In one or more embodiments, the amounts of oxiracetam used within supplements and compositions of the invention include about 50 mg to about 1000 mg, about 100 mg to about 900 mg, or about 150 mg to about 800 mg, or any intervening range therein. In particular preferred embodiments, a supplement or composition comprises at least about 25 mg, about 50 mg, about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, or about 400 mg or any intervening amount therein. In one or more embodiments, the oxiracetam is present in said formulation in an amount of about 250 to 750 mg. In some embodiments, a composition according to the invention comprises a concentration of oxiracetam of at least 10% w/w, at times at least 20% w/w, at times at least 40% w/w, at times at least 50% w/w, at times at least 60% w/w and at times at least 70% w/w. More particularly the composition will comprise oxiracetam in an amount higher than 25 mg/kg of the dry weight of the composition, higher than 50 mg/kg of the dry weight of the composition, higher than 200 mg/kg of the dry weight of the composition, more particularly ranging from 200 mg to 1.5 g/kg of the dry weight of the composition, from 200 mg to 1 g/kg of the dry weight of the composition. In one or more embodiments, the oxiracetam is present in the formulation in an amount of about 300-400 mg.

[00319] In one or more embodiments, the amounts of phosphatidylserine used within supplements and compositions of the invention include about 50 mg to about 1000 mg, about 100 mg to about 900 mg, or about 150 mg to about 800 mg, or any intervening range therein. In particular preferred embodiments, a supplement or composition comprises at least about 25 mg, about 50 mg, about 75 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, or about 400 mg or any intervening amount therein. In one or more embodiments, the phosphatidylserine is present in said formulation in an amount of about 250 to 750 mg. In some embodiments, a composition according to the invention comprises a concentration of phosphatidylserine of at least 10% w/w, at times at least 20% w/w, at times at least 40% w/w, at times at least 50% w/w, at times at least 60% w/w and at times at least 70% w/w. More particularly the composition will comprise phosphatidylserine in an amount higher than 25 mg/kg of the dry weight of the composition, higher than 50 mg/kg of the dry weight of the composition, higher than 200 mg/kg of the dry weight of the composition, more particularly ranging from 200 mg to 1.5 g/kg of the dry weight of the composition, from 200 mg to 1 g/kg of the dry weight of the composition. In one or more embodiments, the phosphatidylserine is present in the formulation in an amount of about 300-400 mg.

[00320] In one or more embodiments, the nutritional composition of the instant application comprises quercetin. In one or more embodiments, the quercetin comprises a natural or synthetic ester or synthetic diol derivative. In one or more embodiments, the amounts of astaxanthin used within the presently disclosed supplements and compositions of the invention comprises a daily dose of 0.5-24 mg/kg body wt., 0.5-18 mg/kg body wt., 1-12 mg/kg body wt., 6-12 mg/kg body wt, and other ranges, and up to 24 mg/kg body wt, including 6-12 mg/kg body wt. According to another embodiment, the therapeutically effective amount of the quercetin is from about 10 mg/day to about 10 g/day. According to another embodiment, the therapeutically effective amount of the quercetin is from about 0.01 mg/kg body weight to about 10 g/kg body weight.

[00321] In one or more embodiments, the nutritional composition of the instant application comprises Rhodiola crenulata. Rhodiola crenulata is available commercially. In general, the dosage of Rhodiola crenulata in the compositions of the instant application can be from about 1 mg to about 1,000 mg daily. In one or more embodiments, the supplement or composition comprises at least about 10 mg, 25 mg, 50 mg, 100 mg, 150 mg, 250 mg, or any intervening amount therein of Rhodiola crenulata. In one or more embodiments, the Rhodiola used in the compositions of the present disclosure is an extract isolated from the dried root and rhizome of Rhodiola crenulata. In one embodiment, compositions of the disclosure administered to a mammal comprise Rhodiola crenulata extract. One bioactive ingredient of interest in Rhodiola crenulata is salidroside. Rosavins is another bioactive constituent identified from the plant. Salidroside and/or rosavins can be used as references for determination of the quality of the preparations.

[00322] In some embodiments, the herbal extract of Rhodiola crenulata comprises at least about 0.40%, at least about 0.50%, at least about 0.60%, at least about 0.70%, at least about 0.80%, or at least about 0.90% w/w salidroside based on the total weight of the herbal extract. In some embodiments, the administration of compositions disclosed herein to a mammal is via an oral route. In some embodiments, the composition is administered to a mammal at a dose of about 1-2600 mg/day, more preferably about 400-2000 mg/day, even more preferably about 800-1600 mg/day, even more preferably about 1200-1600 mg/day, and most preferably about 1000 mg/day. In some embodiments, multiple daily doses of 50, 100, 200, 300, 400, 500, 600, 700, 800 or more mg per dose are provided. In some embodiments, the composition is orally administered to a mammal at a daily dose of about 1-100 mg/kg, more preferably at about 5- 50 mg/kg, even more preferably about 10-30 mg/kg, and most preferably about 20-25 mg/kg. Lower doses of about 1-6 mg/kg or about 1-5 mg/kg may be provided. Multiple daily doses may include 2, 3, 4, 5, 6, 7, 8, 9, 10, or more doses. In various embodiments directed to oral administration disclosed herein, the mammal is a human.

[00323] Rhodiola rosea (Golden Root, Roseroot) consists mainly of phenylpropanoids (rosavin, rosin, rosarin (specific to R. rosea), phenylethanol derivatives (salidroside, rhodioloside, tyrosol), flavanoids (catechins, proanthocyanidins, rodiolin, rodionin, rodiosin, acetylrodalgin, tricin), monoterpenes (rosiridol, rosaridin), triterpenes (daucosterol, beta- sitosterol), and phenolic acids (chlorogenic and hydroxy cinnamic, gallic acids). It also contains organic acids (gallic, caffeic, and chlorogenic acids) and p-Tyrosol. There are many species of Rhodiola, but it appears that the rosavins are unique to R. Rosea, and it is the preferred species. Rosavin, rosarin, rosin and salidroside are among suspected active ingredients of R. rosea. In one or more embodiments, the disclosed compositions comprises Rhodiola rosea products that are standardized based on rosavin content and salidroside content.

[00324] In one or more embodiments, the nutritional composition of the instant application comprises Rhodiola rosea (3% rosavins). Rhodiola rosea is available commercially. In general, the dosage of Rhodiola rosea in the compositions of the instant application can be from about 1 mg to about 2,000 mg daily. In one or more embodiments, the Rhodiola rosea extract (root) comprising a combination of 3-5% rosavin and 2-4% salidroside at about 150-680 mg per dose. In one or more embodiments, the Rhodiola rosea extract used in the composition described herein is standardized to 3% salidroside. The dosage amount of Rhodiola rosea extract in the composition is between about 100 and about 80 mg. In certain embodiments, the dosage amount is 80 mg.

[00325] In one or more embodiments, the disclosed compositions comprises a Rhodiola extract. In some embodiments, the Rhodiola extract comprises at least 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 15%, 20%, or 25% salidrosides including, for example, about 1% to 4%. In some embodiments, the Rhodiola extract composition comprises at least 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 15%, 20%, or 25% rosavins including, for example, about 3% to 6% rosavins. In some embodiments, the composition comprises at least 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 15%, 20%, or 25% rosavin including, for example, about 2% to 5% rosavin or 1% to 5% rosavin. In some embodiments, the Rhodiola extract composition comprises at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 99% Rhodiola extract including, for example about 50% to 99%, 60%-95%, 70%-95% Rhodiola extract.

[00326] In one or more embodiments, the disclosed compositions comprise embodiments wherein Rhodiola (Rhodiola rosea L.) is present in 50-1000 mg, 100-800 mg, 150-700 mg, 150-680 mg, or 500-680 mg. In one or more embodiments, the disclosed compositions comprise embodiments wherein Rhodiola (Rhodiola rosea L.) is present in 100 to 900 mg; 150 to 850 mg; 200 to 800 mg; 250 to 800 mg; 300 to 700 mg; 400 to 700 mg; 450 to 650 mg; 500 to 600 mg; or 600 mg. In particular preferred embodiments, a supplement or composition comprises at least about 10 mg, 25 mg, 50 mg, 100 mg, 150 mg, 250 mg, 350 mg, 450 mg, 550 mg, or 650 mg, or any intervening amount therein of Rhodiola rosea.

In one or more embodiments, the disclosed compositions comprise embodiments wherein the Rhodiola extract or a pharmaceutically acceptable salt or ester thereof is administered in a therapeutically effective amount per kg body weight per day of about 1 mg/kg, 1.5mg/kg, 2.0 mg/kg, 2.5 mg/kg, 3 mg/kg, 4.0 mg/kg, 5.0 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 25 mg/kg, 30 mg/kg, 35 mg/kg, 40 mg/kg, 45 mg/kg 50 mg/kg, 55 mg/kg, 60 mg/kg, 65 mg/kg, 70 mg/kg, 75 mg/kg, 80 mg/kg, 85 mg/kg, 90 mg/kg, 95 mg/kg, 100 mg/kg, 125 mg/kg, 150 mg/kg, 200 mg/kg, 250 mg/kg, 300 mg/kg, 350 mg/kg, 400 mg/kg, 450 mg/kg, 500 mg/kg, 550 mg/kg, 600 mg/kg, 650 mg/kg, 700 mg/kg, 750 mg/kg, 800 mg/kg, 850 mg/kg, 900 mg/kg, 950 mg/kg, 1 g/kg, 5 g/kg, 10 g/kg, or more.

[00327] Yamabushitake (Hericium erinaceum), known as the Lion's Mane Mushroom, appears to have bioactive polysaccharides (carbohydrates) in addition to some ethanolic soluble molecules. In one or more embodiments, the disclosed compositions comprise embodiments wherein Yamabushitake is present in 50-1000 mg, 100-800 mg, 150-700 mg, 150-680 mg, or 500-680 mg. In one or more embodiments, the disclosed compositions comprise embodiments wherein Yamabushitake is present in 100 to 900 mg; 150 to 850 mg; 200 to 800 mg; 250 to 800 mg; 300 to 700 mg; 400 to 700 mg; 450 to 650 mg; 500 to 600 mg; or 600 mg. In particular preferred embodiments, a supplement or composition comprises at least about 10 mg, 25 mg, 50 mg, 100 mg, 150 mg, 250 mg, 350 mg, 450 mg, 550 mg, or 650 mg, or any intervening amount therein of Yamabushitake.

[00328] In one or more embodiments, the disclosed compositions comprise embodiments wherein the Yamabushitake extract or a pharmaceutically acceptable salt or ester thereof is administered in a therapeutically effective amount per kg body weight per day of about 1 mg/kg, 1.5 mg/kg, 2.0 mg/kg, 2.5 mg/kg, 3 mg/kg, 4.0 mg/kg, 5.0 mg/kg, 6 mg/kg, 7 mg/kg, 8 mg/kg, 9 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 25 mg/kg, 30 mg/kg, 35 mg/kg, 40 mg/kg, 45 mg/kg 50 mg/kg, 55 mg/kg, 60 mg/kg, 65 mg/kg, 70 mg/kg, 75 mg/kg, 80 mg/kg, 85 mg/kg, 90 mg/kg, 95 mg/kg, 100 mg/kg, 125 mg/kg, 150 mg/kg, 200 mg/kg, 250 mg/kg, 300 mg/kg, 350 mg/kg, 400 mg/kg, 450 mg/kg, 500 mg/kg, 550 mg/kg, 600 mg/kg, 650 mg/kg, 700 mg/kg, 750 mg/kg, 800 mg/kg, 850 mg/kg, 900 mg/kg, 950 mg/kg, 1 g/kg, 5 g/kg,

[00329] In one or more embodiments, the composition further comprises one or more additional agents selected from the group comprising astaxanthin, brown algae, cyanidin 3 glucoside (cy-g), cyanidin 3,5 diglucoside (cy-dg), 7,8-dihydroxyflavone (7,8-DHF), ferulic acid, muira puama, oxiracetam, Rhodiola crenulata extract, and quercetin, in varying concentrations.

[00330] Extreme Athlete Formulation

[00331] In one or more embodiments, the composition comprises at least the active ingredients citrulline, glutathione and ornithine in varying concentrations.

[00332] In one or more embodiments, the composition comprises at least the active ingredients citrulline, glutathione (GSH), ornithine, and one or more additional active ingredients selected from the group consisting of a source of nitric oxide, catechins, citicoline (also known as CDP-choline or cytidine 5'-diphosphocholine), lycopene and vitamins, in varying concentrations.

[00333] In another embodiment, the composition comprises at least the active ingredients citrulline, glutathione, ornithine, a source of nitric oxide and citicoline, in varying concentrations.

[00334] In one or more embodiments, the citrulline comprises L-citrulline, L-citrulline DL- malate or mixtures thereof. In one or more embodiments, the citrulline comprises L-citrulline DL-malate 2: 1, which combines two-parts L-citrulline, a non-essential amino acid, with one- part DL-malic acid, a racemic mixture of dicarboxylic acids.

[00335] In one or more embodiments, the composition can include a source of nitric oxide selected from the group consisting of beet root extract, vitamin Bl, collard green extract, nut powders, spinach extract, broccoli extract, lettuce extract, celery, kale, watercress, carrot, arugula, mustard greens, or a combination thereof.

[00336] In another embodiment, the composition comprises from about 40 weight parts to about 1000 weight parts of a botanical nitrate source. A botanical nitrate source is any plant matter, extract of plant matter, or product of plant matter containing nitrate. Generally, it is desirable that the botanical nitrate source be generally regarded as safe for human or animal consumption. In one embodiment, the botanical nitrate source is selected from the group consisting of beet root, artichoke, holy basil, gymnema sylvestre, L9H, ashwagandha root, salvia, St. John wort, broccoli, jambolan, syzgium cumini, syzgium cumini nectar, java plum extract, stevia, spinach, gingko, kelp, tribulus, eleuthero, epimedium, eucommia, hawthorn berry, rhodiola, green tea, codonopsys, panax ginseng, astragalus, pine bark, dodder seed, Schisandra, cordyceps, and mixtures thereof. In one particular embodiment, the botanical nitrate source is selected from the group consisting of beet root, artichoke, holy basil, gingko, and mixtures thereof. [00337] In another embodiment, the botanical nitrate source is a beet root extract. In one embodiment of the composition, the beet root extract comprises from about 5 wt % to about 90 wt % of the claimed composition. In another embodiment of the composition, the beet root extract comprises from about 10 wt % to about 80 wt % of the claimed composition. In another embodiment of the composition, the beet root extract comprises at least 10, 15, 20, 25, 30, 35, 40, 45, 50 wt % or more of the claimed composition. In one or more embodiments, the composition comprises from about 250 to 800mg, from about 300 to 600mg, from about 350- 500mg and from about 350-450mg of beet root extract.

[00338] For foods and food products formulated for human consumption, the amount of nitrate source as a percentage of the composition can be in the range of about 0.1% to about 12% of the composition, although a greater percentage can be supplied. In various embodiments, the amount of nitrate source can be at least about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2.0%, 2.1%, 2.2%, 2.3%, 2.4%, 2.5%, 2.6%, 2.7%, 2.8%, 2.9%, 3.0%, 3.1%, 3.2%, 3.3%, 3.4%, 3.5%, 3.6%, 3.7%, 3.8%, 3.9%, 4.0%, 4.1%, 4.2%, 4.3%, 4.4%, 4.5%, 4.6%, 4.7%, 4.8%, 4.9%, 5.0%, or more, e.g., 6%, 7%, 8%, 9%, 10%, 11%, 12% or more, up to about 15% or even 20% of the composition.

[00339] In another embodiment, the composition comprises at least the active ingredients citrulline, glutathione, ornithine, beet root extract and citicoline, in varying concentrations.

[00340] In another embodiment, the composition comprises at least the active ingredients citrulline, glutathione, ornithine, beet root extract, citicoline, and one or more additional active ingredients selected from the group consisting of a catechin and an extract comprising a catechin. In one or more embodiments, the composition comprises from about 250 to 800 mg, from about 300 to 700 mg, from about 350-6500 mg and from about 400-600 mg of catechin extract.

[00341] The four types of catechins (or epicatechins) found in green tea (from Camellia sinensis ) are the epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin gallate (ECG), and epicatechin (EC). EGCG accounts for about 50-80% of the catechins in green tea. Catechins may also be found from other sources such as cocoa.

[00342] In one or more embodiments, the composition comprises an extract from Camellia sinensis or a green tea containing a catechin selected from the group consisting of epigallocatechin gallate, epigallocatechin, epicatechin gallate, epicatechin and combinations thereof, in varying concentrations. [00343] The catechin can be, but is not limited to, catechin monomers (e.g., flavan-3-ol monomers), catechin isomers, and combinations thereof. Some embodiments comprise catechin esters, such as catechin gallate (CG), gallocatechin (GC), gallocatechin gallate (GCG), epicatechin (EC), epicatechin gallate (ECG), epigallocatechin (EGC), and epigallocatechin gallate (EGCG), and combinations of two or more thereof.

[00344] Catechins can be derived from a variety of sources, such as tea plants (e.g., Camellia sinensis), cocoas (e.g., made from seeds of Theobroma cacao), and chocolates. In some embodiments, the catechins are extracted from a plant, such as a green tea plant (e.g., Camellia sinensis).

[00345] Some embodiments comprise a plant extract that comprises catechins. In some embodiments, the plant extract comprises more than about 70% (w/w) catechins, more than about 80% (w/w) catechins, more than about 90% (w/w) catechins, or more than about 95% (w/w) catechins. In some embodiments, the plant extract comprises more than 70% (w/w) catechins, more than 80% (w/w) catechins, more than 90% (w/w) catechins, or more than 95% (w/w) catechins.

[00346] In some embodiments, the plant extract is a green tea extract. The extract can be of any suitable green tea variety, such as sencha, fukushami sencha, gyokuro, kabusecha, matcha, tencha, genmaicha, hojicha, shincha, ichibancha, nibancha, or sanbancha.

[00347] In some embodiments, the composition comprises from about 250 mg to about 1,500 mg green tea extract comprising at least 20, 30, 40, 50, 60, 70, 80, or 90% (w/w) catechins.

[00348] In one or more embodiments, the composition comprises as an active ingredient a green tea extract containing (-)-gallocatechin gallate (GCG) at 5 to 25% by weight based on a total weight of the composition or the extract and (-)-epigallocatechin gallate (EGCG) at 7 to 15% by weight based on the total weight of the composition or the extract.

[00349] In another embodiment, the composition comprises at least the active ingredients citrulline, glutathione, ornithine, beet root extract, citicoline, green tea extract, and one or more vitamins, in varying concentrations.

[00350] In one example, the citrulline, glutathione and ornithine in the composition, can include glutathione, L-citrulline and ornithine, or a combination thereof. In one example, the glutathione, L-citrulline and ornithine can comprise from about 40 wt % to about 98 wt % of the composition. In another example, the glutathione, L-citrulline and ornithine can comprise from 10 wt % to 60 wt % of the composition.

[00351] In one or more embodiments, the composition comprises at least the active ingredients citicoline, citrulline, and glutathione, catechins and one or more additional active ingredients selected from the group consisting of lipophilic nutrients and vitamins, in varying concentrations.

[00352] In one or more embodiments, the lipophilic nutrient is selected from the group consisting of lutein, zeaxanthin, astaxanthin, beta-carotene, lycopene, Vitamin A, Vitamin D, Vitamin E, Vitamin K, Coenzyme Q10, linoleic acid, alpha linolenic acid, arachidonic acid, docosahexaenoic acid, eicosapentaenoic acid, and combinations thereof.

[00353] In one or more embodiments, the lipophilic nutrient is lycopene. Lycopene is a natural pigment found in ripe fruit, particularly in tomato, or synthesized, especially from a fungus, Blakeslea trispora. It belongs to the carotenoid family and its structure is similar to that of .beta. -carotene. The lycopene content, in a food supplement in accordance with the invention, may be between 0.1% and 30% by weight, especially between 0.1% and 20% by weight, and particularly between 0.1% and 10% by weight, relative to the total weight of the combination of active agents. In one or more embodiments, the lycopene is provided in a range selected from: 5 to 90 mg; 10 to 85 mg; 15 to 80 mg; 20 to 80 mg; 20 to 70 mg; or 20 to 40 mg.

[00354] In another embodiment, the composition comprises at least the active ingredients beet root extract, citicoline, citrulline, glutathione, green tea extract, lycopene, and ornithine, in varying concentrations.

[00355] In another example, the L-citrulline can be present in the composition from about 1 wt % to about 80 wt %. In another example, the L-citrulline can be present in the composition from about 0.5 wt % to about 90 wt %. In yet another example, the L-citrulline can be present in the composition from about 0.25 wt % to about 95 wt %. In a further example, the L-citrulline can be present in the composition from about 0.125 wt % to about 99 wt %. In yet a further example, the L-citrulline can be present in the composition from about 0.1 wt % to about 5 wt %. In yet another example, the L-citrulline can be present from about 0.5 wt % to about 2.5 wt %.

[00356] In yet another example, the citrulline in the composition can include a combination of L-malate and L-citrulline. In one example, the L-malate can range from about 1 wt % to about 80 wt % and the L-citrulline can range from about 1 wt % to about 80 wt %. In another example, the L-malate can range from about 0.5 wt % to about 90 wt % in and the L-citrulline can range from about 0.5 wt % to about 90 wt %. In yet another example, the L-malate can range from about 0.25 wt % to about 95 wt % and the L-citrulline can range from about 0.25 wt % to about 95 wt %. In yet a further example, the L-malate can range from about 40 wt % to about 95 wt % and the L-citrulline can range from about 0.1 wt % to about 5 wt %. [00357] The ratio of the weight percentage of L-malate and L-citrulline can also vary. In one embodiment, the L-malate and L-citrulline can be present in the composition at a weight percent concentration ranging from about 1 :5 to about 5: 1, respectively. In another embodiment, the L-malate and L-citrulline can be present in the composition at a weight percent concentration ranging from about 1 : 1 to about 5: 1, respectively. In yet another embodiment, the L-malate and L-citrulline can be present in the composition at a weight percent concentration of about 2: 1, respectively.

[00358] In one or more embodiments, the source of nitric oxide can be in the composition at a range from about 1 wt % to about 80 wt %. In another example, the source of nitric oxide can be in the composition at a range from about 0.01 wt % to about 90 wt %. In another example, the source of nitric oxide can be present in the composition from about 15 wt % to about 30 wt %.

[00359] In one or more embodiments, the source of nitric oxide can include beet root extract, vitamin Bl, or a combination thereof. In another example, the source of nitric oxide can include the beet root extract and the vitamin B 1. In one example, including beet root extract and vitamin B 1 , the beet root extract can range from about 5 wt % to about 90 wt % and the vitamin B 1 can range from about 0.01 wt % to about 80 wt % of the composition. In another example, including beet root extract and vitamin Bl, the beet root extract can range from about 1 wt % to about 95 wt % and the vitamin B 1 can range from about 0.005 wt % to about 99 wt % of the composition. In yet another example, including beet root extract and vitamin Bl, the beet root extract can range from about 0.1 wt % to about 99 wt % and the vitamin Bl can range from about 0.0025 wt % to about 0.995 wt % of the composition. In a further example, the beet root extract can range from about 15 wt % to about 30 wt % and the vitamin Bl can range from about 0.5 wt % to about 5 wt %.

[00360] Additional Extreme Athlete Formulation

[00361] In another embodiment, the synergistic composition comprises at least the active ingredients N-acetylcysteine amide, beta-alanine, catechins, a choline, citrulline, glutathione, L-ornithine, D-ribose, and Rhodiola rosea extract in varying concentrations, in varying concentrations.

[00362] In another embodiment, the synergistic composition comprises at least the active ingredients N-acetylcysteine amide, beta-alanine, catechins, citicoline, citrulline, glutathione, L-ornithine, D-ribose, and Rhodiola rosea extract in varying concentrations, in varying concentrations. [00363] In another embodiment, the synergistic composition comprises at least the active ingredients N-acetylcysteine amide, beta-alanine, green tea extract, citicoline, citrulline, glutathione, L-omithine, D-ribose, and Rhodiola rosea extract in varying concentrations, in varying concentrations.

[00364] In another embodiment, the synergistic composition comprises at least the active ingredients N-acetylcysteine amide, beta-alanine, a cyanidin, green tea extract (EGCG), citicoline, citrulline, glutathione, L-ornithine, D-ribose, and Rhodiola rosea extract in varying concentrations, in varying concentrations.

[00365] In another embodiment, the synergistic composition comprises at least the active ingredients from about 300 to about 500 mg N-acetylcysteine amide, from about 2 to about 5 g beta-alanine, from about 500 to about 700 mg green tea extract (EGCG), from about 500 to about 1000 mg citicoline, from about 8 to about 12 g citrulline, from about 250 to about 1000 mg glutathione, from about 500 to about 800 mg L-ornithine, from about 1 to about 5 g D- ribose, and from about 300 to about 500 mg Rhodiola rosea extract (3-5% rosavins and 2-4% salidroside) in varying concentrations, in varying concentrations.

[00366] In another embodiment, the synergistic composition comprises at least the active ingredients N-acetylcysteine amide, beta-alanine, cyanidin-3-glucoside (Cy-g) or cyanidin-3,5- diglucoside (Cy-dg), green tea extract (EGCG), citicoline, citrulline, glutathione, L-ornithine, D-ribose, and Rhodiola rosea extract in varying concentrations, in varying concentrations.

[00367] In another embodiment, the synergistic composition comprises at least the active ingredients N-acetylcysteine amide, beta-alanine, cyanidin-3-glucoside (Cy-g) or cyanidin-3,5- diglucoside (Cy-dg), green tea extract (EGCG), citicoline, citrulline, glutathione, L-ornithine, D-ribose, Rhodiola rosea extract, and L-theanine in varying concentrations, in varying concentrations.

[00368] In another embodiment, the synergistic composition comprises at least the active ingredients from about 300 to about 500 mg N-acetylcysteine amide, from about 2 to about 5 g beta-alanine, from about 500 to about 700 mg green tea extract (EGCG), from about 500 to about 1000 mg citicoline, from about 8 to about 12 g citrulline, from about 200 to about 500 cyanidin, from about 250 to about 1000 mg glutathione, from about 500 to about 800 mg L- ornithine, from about 1 to about 5 g D-ribose, and from about 300 to about 500 mg Rhodiola rosea extract (3-5% rosavins and 2-4% salidroside) in varying concentrations, in varying concentrations.

[00369] In another embodiment, the synergistic composition comprises at least the active ingredients from about 300 to about 500 mg N-acetylcysteine amide, from about 2 to about 5 g beta-alanine, from about 500 to about 700 mg green tea extract (EGCG), from about 500 to about 1000 mg citicoline, from about 8 to about 12 g citrulline, from about 200 to about 400 of cyanidin-3-glucoside (Cy-g) or cyanidin-3,5-diglucoside (Cy-dg), from about 250 to about 1000 mg glutathione, from about 500 to about 800 mg L-ornithine, from about 1 to about 5 g D-ribose, and from about 300 to about 500 mg Rhodiola rosea extract (3-5% rosavins and 2- 4% salidroside) in varying concentrations, in varying concentrations.

[00370] In another embodiment, the synergistic composition comprises at least the active ingredients from about 300 to about 500 mg N-acetylcysteine amide, from about 2 to about 5 g beta-alanine, from about 500 to about 700 mg green tea extract (EGCG), from about 500 to about 1000 mg citicoline, from about 8 to about 12 g citrulline, from about 200 to about 400 of cyanidin-3-glucoside (Cy-g) or cyanidin-3,5-diglucoside (Cy-dg), from about 250 to about 1000 mg glutathione, from about 500 to about 800 mg L-ornithine, from about 1 to about 5 g D-ribose, from about 300 to about 500 mg Rhodiola rosea extract (3-5% rosavins and 2-4% salidroside), and from about 250 to about 450 mg L-theoninein varying concentrations, in varying concentrations.

[00371] In another embodiment, the synergistic composition comprises at least the active ingredients from about 300 to about 500 mg N-acetylcysteine amide, from about 2 to about 5 g beta-alanine, from about 500 to about 700 mg green tea extract (EGCG), from about 500 to about 1000 mg citicoline, from about 8 to about 12 g citrulline, from about 200 to about 400 of cyanidin-3-glucoside (Cy-g) or cyanidin-3,5-diglucoside (Cy-dg), from about 250 to about 1000 mg glutathione, from about 500 to about 800 mg L-ornithine, from about 250 to about 750 mg phosphatidylserine, from about 1 to about 5 g D-ribose, from about 300 to about 500 mg Rhodiola rosea extract (3-5% rosavins and 2-4% salidroside), and from about 250 to about 450 mg L-theoninein varying concentrations, in varying concentrations.

[00372] In one or more embodiments, the composition comprises at least the active ingredients N-acetylcysteine amide (NAC amide or NACA), alanine, anthocyanin; or anthocyanidin, citicoline, citrulline, glutathione and ornithine in varying concentrations.

[00373] In one or more embodiments, the composition comprises at least the active ingredients N-acetylcysteine amide (NAC amide or NACA), alanine, anthocyanin; or anthocyanidin, green tea extract or catachins, citicoline, citrulline, glutathione and ornithine in varying concentrations.

[00374] In one or more embodiments, the composition comprises at least the active ingredients N-acetylcysteine amide (NAC amide or NACA), alanine, anthocyanin; or anthocyanidin, citicoline, citrulline, glutathione, ornithine and D-ribose in varying concentrations.

[00375] In one or more embodiments, the composition comprises at least the active ingredients N-acetylcysteine amide (NAC amide or NACA), alanine, anthocyanin; or anthocyanidin, citicoline, citrulline, glutathione, ornithine and Rhodiola Rosea Extract in varying concentrations.

[00376] In one or more embodiments, the composition comprises at least the active ingredients N-acetylcysteine amide (NAC amide or NACA), alanine, anthocyanin; or anthocyanidin, citicoline, citrulline, glutathione, ornithine and L-theonine in varying concentrations.

[00377] In one or more embodiments, the composition comprises at least the active ingredients N-acetylcysteine amide (NAC amide or NACA), alanine, anthocyanin; or anthocyanidin, green tea extract or catachins, citicoline, citrulline, glutathione, ornithine, D- ribose, Rhodiola Rosea Extract and L-theonine in varying concentrations.

[00378] In one or more embodiments, the compositions above further comprise one or more additional agents selected from the group comprising tart cherry extract, phosphatidylserine, L-alanyl-L-glutamine, and Rhodiola Crenulata extract. In one or more embodiments, the composition further comprises tart cherry extract, phosphatidylserine, L-alanyl-L-glutamine, and Rhodiola Crenulata extract.

[00379] In one or more embodiments, the compositions above further comprise one or more additional agents selected from the group comprising from about 250 to about 750 mg tart cherry extract, from about 250 to about 750 mg phosphatidylserine, L-alanyl-L-glutamine, and Rhodiola Crenulata extract. In one or more embodiments, the composition further comprises tart cherry extract, phosphatidylserine, from about 1 to about 2 g L-alanyl-L-glutamine, and from about 150 to about 350 mg Rhodiola Crenulata extract (1-5% salidroside).

[00380] In one or more embodiments, the active ingredient N-acetylcysteine amide (NAC amide or NACA) of the composition comprises N-acetylcysteine amide (NAC amide or NACA) or derivatives thereof, or a physiologically acceptable derivative, salt, or ester thereof, glutathione N-acetylcysteine amide (NAC amide), or a physiologically or pharmaceutically acceptable derivative or salt or ester thereof, for use in a variety of disorders, conditions, pathologies and diseases in which oxidative stress and/or free radical formation cause damage, frequently systemic damage, to cells, tissues and organs of the body. The invention encompasses a pharmaceutically acceptable composition comprising NAC amide, e.g., water- soluble NAC amide, or physiologically acceptable derivatives, salts, or esters thereof, which can be used in treatment and therapeutic methods in accordance with this invention. In one or more embodiments, the amounts of N-acetylcysteine amide (NAC amide or NACA) or derivatives thereof, or a physiologically acceptable derivative, salt, or ester thereof, glutathione N-acetylcysteine amide (NAC amide), or a physiologically or pharmaceutically acceptable derivative or salt or ester thereof, used within supplements and compositions of the invention include about 100 mg to about 1500 mg, about 200 mg to about 1400 mg, about 300 mg to about 1300 mg, or about 400 mg to about 1200 mg, or any intervening range therein. In particular preferred embodiments, a supplement or composition comprises at least about 200 mg, about 400 mg, about 600 mg, about 800 mg, about 900 mg, about 1000 mg, about 1100 mg, or about 1200 mg or any intervening amount therein. In one or more embodiments, the anthocyanin or anthocyanidin is present in said formulation in an amount of about 450 to 1200 mg.

[00381] Beta-alanine is a modified version of the amino acid alanine and is synthesized in the liver and transported to muscle cells (type II muscles more than type I) where it is turned into carnosine. Beta-alanine or a salt, ester or chelate thereof, suitable for use in supplements and compositions of the invention may be supplied in natural and synthetic forms. In one or more embodiments, the amounts of beta-alanine used within supplements and compositions of the invention include about 0.5 g to about 6 g, about 1 g to about 5g, or about 2 g to about 5 g or any intervening range therein. In particular preferred embodiments, a supplement or composition comprises at least about 1 g, about 2 g, about 3 g, about 3.5 g, 4 g, about 4.5 g, or about 5 g or any intervening amount therein of beta-alanine. In one or more embodiments, the beta-alanine is present in said formulation in an amount of about 2-5g.

[00382] In one or more embodiments, the citrulline comprises L-citrulline, L-citrulline DL- malate or mixtures thereof. In one or more embodiments, the citrulline comprises L-citrulline DL-malate 2: 1, which combines two parts L-citrulline, a non-essential amino acid, with one part DL-malic acid, a racemic mixture of dicarboxylic acids. In one or more embodiments, the disclosed compositions comprise embodiments wherein citrulline is present in 2-14 g, 4-12g, 6-12 g, or 8-12 g. In one or more embodiments, the disclosed compositions comprise embodiments wherein citrulline is present as L-citrulline DL-malate 2: 1, which combines two parts L-citrulline with one part DL-malic acid, wherein citrulline is present in 2-14 g, 4-12g, 6- 12 g, or 8-12 g. The L-isomer of citrulline can boost nitric oxide levels, which can increase blood flow and reduce fatigue by replenishing depleted nutrients. In one example, a supplement formulation can include citrulline at from about 1 wt % to about 45 wt %. In other examples, supplement formulations can include citrulline at from about 10 wt % to about 20 wt %, at from about 5 wt % to about 20 wt %, at from about 10 wt % to about 25 wt %, at from about 10 wt % to about 30 wt %, at from about 5 wt % to about 25 wt %, at from about 10 wt % to about 30 wt %, or at from about 5 wt % to about 15 wt %. In one or more embodiments, the citrulline includes derivatives thereof, such as citrulline malate, and the like. Supplement formulations containing both malic acid and citrulline can include these ingredients in any beneficial relative amount, and such can be varied depending on the forms of malic acid and citrulline used, and to suit individual needs. Non-limiting examples of ratios of malic acid to citrulline include a 1 : 1 ratio, a 1 :2 ratio, a 1 :3 ratio, a 1 :4 ratio, a 1 :5 ratio, a 1.5: 1 ratio, a 2: 1 ratio, a 3 : 1 ratio, and the like. In one example, the malic acid and citrulline can be present at a 1 :2 ratio.

[00383] In one or more embodiments, the disclosed compositions comprise embodiments wherein citicoline (also known as CDP-choline or cytidine 5'-diphosphochoiine) is present in an amount of 100-1500 mg, 200-1400 mg, 300-1300 mg, 400-1200 mg, 500-1100 mg, or 600- 1000 mg.

[00384] Extracts of the invention also can contain one or more simple phenolic compounds, such as ellagic acid, ferulic acid, and coumaric acid (but also, e.g., hydrobenzoic acid, hydroxycinnamic acid), complex phenols such as flavonoids (e.g., anthocyanidins), anthocyanins (e.g., cyanidin, pelargonidin), quercetin, kaempferol, and analogs thereof), flavanols, flavan-3-ols, and/or tannins).

[00385] In one aspect, the present invention provides a pharmaceutical composition comprising an anthocyanin or anthocyanidin. By way of example, the anthocyanin can be selected from cyanidin 3 glucoside (cy-g) or cyanidin 3,5-O-diglucoside (cy-dg), delphinidin- 3-glucoside, cyanidin-3-galactoside, and pelargoni din-3 -galactoside. Also, by way of example, the anthocyanidins can be selected from cyanidin, delphinidin, pelargonidin, malvidin and petunidin. In yet another aspect, the present disclosure provides a pharmaceutical composition comprising a metabolite of an anthocyanin metabolite or a metabolite of an anthocyanidin metabolite. By way of example, the metabolites are metabolites selected from protocatechuic acid, 2, 3, 4 trihydroxybenzaldehyde. In one or more embodiments, the amounts of anthocyanin or anthocyanidin used within supplements and compositions of the invention include about 100 mg to about 1500 mg, about 200 mg to about 1400 mg, about 300 mg to about 1300 mg, or about 400 mg to about 1200 mg, or any intervening range therein. In particular preferred embodiments, a supplement or composition comprises at least about 200 mg, about 400 mg, about 600 mg, about 800 mg, about 900 mg, about 1000 mg, about 1100 mg, or about 1200 mg or any intervening amount therein. In one or more embodiments, the anthocyanin or anthocyanidin is present in said formulation in an amount of about 450 to 1200 mg. In yet another aspect and in other embodiments, the anthocyanidin provided in any recited composition is provided less than 200 mM and in other embodiments about 100 mM. In some embodiments, the anthocyanin or anthocyanidin provided in any recited composition or method of use is provided in a range of between 10 to 200 mM. In other embodiments, the anthocyanin metabolite or anthocyanidin metabolite provided in any recited composition or method of use is provided in a range of between 20 to 200 mM. In yet other embodiments, the anthocyanin, anthocyanidin, or metabolites thereof provided in any recited composition or method of use is provided in a range of between 20 to 100 mM. In yet other embodiments, the anthocyanin, anthocyanidin, or metabolites thereof provided in any recited composition or method of use is provided in a range of between 20 to 50 mM. In some embodiments, the metabolite is provided in any recited composition less than 100 mM and in others at 25 mM.

[00386] In accordance with one or more embodiments of the present invention, the extract contains one or more anthocyanins and anthocyanidins selected from the group consisting of peonidin, cyanidin, pelargonidin, delphinidin, petunidin, malvidin, apigenindin, auratinidin, capensinidin, europinidin, hirsutidin, 6-hydroxycyanidin, luteolinidin, 5-methylcyanidin, pulchellidin, rosinidin, tricetinidin, derivatives and mixtures thereof. In one embodiment, the anthocyanins and anthocyanidins are selected from the group consisting of cyanidin, peonidin, malvidin, petunidin, delphinidin, their glycoside derivatives, and mixtures thereof. In yet another embodiment, the extract contains at least one cyanidin-based anthocyanin. Anthocyanins that may be useful in the inventions described herein include, but are not limited to, cyanidin-3-glucoside; cyanidin 3-glucosylrutinoside; cyanidin-3-gentibioside; cyanidin-3- rutinoside, cyanidin-3-sambunigrin, cyanidin-3-samb-5-glucoside, cyanidin-3-galactoside, peoni din-3 -rutinoside, peoni din-3 -glucoside, peoni din-3 -galactoside, peonidin, cyanidin, cyani din-3 sophoroside, pelargonidin, delphinidin, delphini din-3 -glucoside, delphini din-3 - galactoside, petunidin, petuni din-3 -glucoside, petuni din-3 -galactoside, malvidin, malvi din-3 - arabinoside, malvi din-3 -glucoside, malvi din-3 -galactoside, kaempferol, hesperidin, gentiodelphin, platyconin, cinerarin and the like. In one or more embodiments, a dietary or nutritional supplement or nutraceutical is provided and contains from about 0.1% to about 99%, preferably from about. 30% to about 90% of an anthocyanin-containing extract. In this regard, a single dosage form (i.e., a single tablet, capsule, serving (whether liquid or solid)) contains from about 1 mg. to about 500 mg. of total anthocyanin, preferably from about 5 mg. to about 100 mg., more preferably from about 20 mg. to about 70 mg. of total anthocyanin. In a preferred formulation, a tablet (a single dosage form) is provided that contains about 35 mg. of total anthocyanin. The phrase "total anthocyanin" refers to the total amount of anthocyanin present in the single dosage form.

[00387] In one or more embodiments, the disclosed compositions comprise embodiments wherein glutathione is present in 300-900 mg, 400-800 mg, 500-700 mg, 550-650 mg, or 600 mg. In one or more embodiments, the disclosed compositions comprise embodiments wherein glutathione is present as reduced glutathione and is present in 100 to 900 mg; 150 to 850 mg; 200 to 800 mg; 250 to 800 mg; 300 to 700 mg; 400 to 700 mg; 450 to 650 mg; 500 to 600 mg; or 600 mg.

[00388] In one or more embodiments, the disclosed compositions comprise embodiments wherein at least one flavan-3-ol compound is present. In one or more embodiments, the at least one flavan-3-ol compound is selected from the group consisting of monomers, oligomers, polymers, glycosides and pharmaceutically acceptable salts of the following: (+)-catechin, (-)- epicatechin, epigallocatechin, epicatechin gallate, epigallocatechin gallate, epiafzelechin, and fisetinidol. In one or more embodiments, the disclosed compositions comprise embodiments wherein at least one flavan-3-ol compound is present in 200-800 mg, 300-700 mg, 400-600 mg, 500-600 mg or 500 mg.

[00389] In one or more embodiments, the disclosed compositions comprise embodiments wherein green tea extract is present in 200-800 mg, 300-700 mg, 400-600 mg, 500-600 mg or 500 mg; and wherein the green tea extract comprises at least 10%, 15%, 20%, 25%, 30%, 35%, 40% epigallocatechin gallate (EGCG), or more.

[00390] In one or more embodiments, the disclosed compositions comprise embodiments wherein ornithine is present in 0.2-10 g, 0.3-8g, 0.4-2 g, 0.5-1 g, 0.7-0.9 g or 0.8 g. In one or more embodiments, the disclosed compositions comprise embodiments wherein ornithine is present as L-orni thine HC1.

[00391] In one or more embodiments, the disclosed compositions comprise embodiments wherein ribose is present in 0.5-10 g, l-8g, 2-6 g, or 2-5 g. In one or more embodiments, the disclosed compositions comprise embodiments wherein ribose is present as D-ribose.

[00392] L-theanine is an amino acid and a glutamic acid analog commonly found in tea (infusions of Camellia sinensis), primarily in green and black teas. Studies have also shown that L-theanine supplementation increases mental alertness, attention, and memory and may provide neuroprotective effects. In addition, while structurally related to the excitatory neurotransmitter glutamate, theanine only has weak affinity for the glutamate receptor on postsynaptic cells. Theanine may also increase GABA and dopamine levels and have a low affinity for AMP A, kainate and NMDA receptors. In particular embodiments, L-metheanine may be substituted for L-theanine. L-theanine suitable for use in supplements and compositions of the invention may be supplied in natural and synthetic forms. In one or more embodiments, the amounts of L-theanine used within supplements and compositions of the invention include about 50 mg to about 600 mg, about 100 mg to about 500 mg, or about 150 mg to about 450 mg, or any intervening range therein. In particular preferred embodiments, a supplement or composition comprises at least about 50 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 400 mg, or about 450 mg or any intervening amount therein. In one or more embodiments, the L-theanine is present in said formulation in an amount of about 250 to 450 mg.

[00393] Rhodiola rosea (Golden Root, Roseroot) consists mainly of phenylpropanoids (rosavin, rosin, rosarin (specific to R. rosea), phenylethanol derivatives (salidroside, rhodioloside, tyrosol), flavanoids (catechins, proanthocyanidins, rodiolin, rodionin, rodiosin, acetylrodalgin, tricin), monoterpenes (rosiridol, rosaridin), triterpenes (daucosterol, beta-sitosterol), and phenolic acids (chlorogenic and hydroxycinnamic, gallic acids). It also contains organic acids (gallic, caffeic, and chlorogenic acids) and p-Tyrosol. There are many species of Rhodiola, but it appears that the rosavins are unique to R. Rosea, and it is the preferred species. Rosavin, rosarin, rosin and salidroside are among suspected active ingredients of R. rosea. In one or more embodiments, the disclosed compositions comprises Rhodiola rosea products that are standardized based on rosavin content and salidroside content.

[00394] In one or more embodiments, the nutritional composition of the instant application comprises Rhodiola rosea 3% rosavins. Rhodiola rosea is available commercially. In general, the dosage of Rhodiola rosea in the compositions of the instant application can be from about 1 mg to about 2,000 mg daily. In one or more embodiments, the Rhodiola rosea extract (root) comprising a combination of 3-5% rosavin and 2-4% salidroside at about 150-680 mg per dose. In one or more embodiments, the Rhodiola rosea extract used in the composition described herein is standardized to 3% salidroside. The dosage amount of Rhodiola rosea extract in the composition is between about 100 and about 80 mg. In certain embodiments, the dosage amount is 80 mg.

[00395] In one or more embodiments, the disclosed compositions comprises a Rhodiola extract. In some embodiments, the Rhodiola extract comprises at least 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 15%, 20%, or 25% salidrosides including, for example, about 1% to 4%. In some embodiments, the Rhodiola extract composition comprises at least 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 15%, 20%, or 25% rosavins including, for example, about 3% to 6% rosavins. In some embodiments, the composition comprises at least 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 15%, 20%, or 25% rosavin including, for example, about 2% to 5% rosavin or 1% to 5% rosavin. In some embodiments, the Rhodiola extract composition comprises at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 99% Rhodiola extract including, for example about 50% to 99%, 60%-95%, 70%-95% Rhodiola extract.

[00396] In one or more embodiments, the disclosed compositions comprise embodiments wherein Rhodiola (Rhodiola rosea L.) is present in 50-1000 mg, 100-800 mg, 150-700 mg, 150-680 mg, or 500-680 mg. In one or more embodiments, the disclosed compositions comprise embodiments wherein Rhodiola (Rhodiola rosea L.) is present in 100 to 900 mg; 150 to 850 mg; 200 to 800 mg; 250 to 800 mg; 300 to 700 mg; 400 to 700 mg; 450 to 650 mg; 500 to 600 mg; or 600 mg. In particular preferred embodiments, a supplement or composition comprises at least about 10 mg, 25 mg, 50 mg, 100 mg, 150 mg, 250 mg, 350 mg, 450 mg, 550 mg, or 650 mg, or any intervening amount therein of Rhodiola rosea.

[00397] Tart Cherry extract is another powerful antioxidant with profound anti-inflammatory effects and muscle recovery effects. The productive agents in tart cherries are anthocyanins, an antioxidant found in red and purple fruits, raspberries and blueberries. Tart cherries however have the highest concentrations and have been shown to increase the activity of the body's key antioxidant enzyme, superoxide dismutase. In addition to strong anti-inflammatory properties, they also aid in muscle recovery.

[00398] The extract of cherry may be from any portion of the fruit or plant, including the leaves, pit, bark, roots, etc. In various embodiments, the cherry is from the genus Prunus and may be either sweet cherry (Prunus avium), tart cherry (Prunus cerasus), Amur choke cherry (Prunus maackii), Wild Black Cherry (Prunus serotina), or mixtures thereof. In one embodiment the cherry fruit extract is rich in flavonoids. These flavenoids are natural, potent antioxidants which support joint health. Flavonoids have also been shown to support the health of collagen which makes up part of the skin, bones and connective tissue. Cherry fruit extract supports the body's natural anti-inflammatory response, increases the elimination of uric acid from the body, and contains powerful antioxidants to help prevent damage to healthy cells. The extract may be prepared by known extraction, distillation, and purification techniques well known in the art. In one embodiment the extraction is a supercritical fluid extraction. In one embodiment the cherry fruit extract is organic. In one embodiment the extract of cherry is at least a 5: l, an 8: l, a l0: l concentrate by weight or even higher. [00399] In various embodiments, the tart cherry extract/powder ingredient used in a composition as described herein has a potency or purity of about 50-55%, 60-65%, 70-75%, 75-80%, 80-85%, 85-90%, 90-95%, or 95-100% for anthocyanins. In certain embodiments, the tart cherry extract/powder ingredient used in a composition as described herein is tart cherry extract/powder 85% anthocyanins. In one or more embodiments, the composition may comprise, or may consist essentially of, or may consist of tart cherry extract at least about 100, 200, 250, 300, 350, 400, 450 or 480 mg or more.

[00400] The term phosphatidylserine as used herein refers to phosphatidyl-L-serine. The term phosphatidylserine is often also referred to in the literature as serine glycerophospholipid, phosphatidyl serine, and PS. In one or more embodiments, the amounts of phosphatidylserine used within supplements and compositions of the invention include about 50 mg to about 1000 mg, about 100 mg to about 900 mg, or about 150 mg to about 800 mg, or any intervening range therein. In particular preferred embodiments, a supplement or composition comprises at least about 50 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, or about 750 mg or any intervening amount therein. In one or more embodiments, the phosphatidylserine is present in said formulation in an amount of about 250 to 750 mg. In some embodiments, a composition according to the invention comprises a concentration of phosphatidylserine of at least 10% w/w, at times at least 20% w/w, at times at least 40% w/w, at times at least 50% w/w, at times at least 60% w/w and at times at least 70% w/w. More particularly the composition will comprise phosphatidylserine in an amount higher than 25 mg/kg of the dry weight of the composition, higher than 50 mg/kg of the dry weight of the composition, higher than 200 mg/kg of the dry weight of the composition, more particularly ranging from 200 mg to 1.5 g/kg of the dry weight of the composition, from 200 mg to 1 g/kg of the dry weight of the composition.

[00401] L-alanyl-L-glutamine (e.g., SUSTAMINE®, Kyowa Hakko Bio Co., Ltd.) is a dipeptide consisting of L-alanine and L-glutamine, and is known to be used as an energy source for cell division, to have an effect of promoting wound healing, and the like, similar to L- glutamine. In one or more embodiments, the composition further comprises L-alanyl-L- glutamine or a salt, ester or chelate thereof, suitable for use in supplements and compositions of the invention. In one or more embodiments, the amounts of L-alanyl-L-glutamine used within supplements and compositions of the invention include about 0.1 g to about 5 g, about 0.5 g to about 3 g, or about 1 g to about 2 g or any intervening range therein. In particular preferred embodiments, a supplement or composition comprises at least about 0.1 g, about 0.25 g, about 0.5 g, about 1 g, about 1.5 g, or about 2 g or any intervening amount therein of L- alanyl-L-glutamine. In one or more embodiments, the L-alanyl-L-glutamine is present in said formulation in an amount of about 1-2 g.

[00402] In one or more embodiments, the composition further comprises Rhodiola crenulate extract, suitable for use in supplements and compositions of the invention. The Rhodiola used in the compositions of the present disclosure can be isolated from any species of Rhodiola. In some embodiments, the Rhodiola used is an extract isolated from the dried root and rhizome of Rhodiola crenulata. In one or more embodiments, the Rhodiola crenulata extract is an extract selected from the group consisting of an extract of the roots of Rhodiola crenulata, an extract of the low stem of Rhodiola crenulata, and an extract of the roots and of the low stem of Rhodiola crenulata. In some embodiments, the herbal extract of Rhodiola crenulata comprises at least about 0.40%, at least about 0.50%, at least about 0.60%, at least about 0.70%, at least about 0.80%, or at least about 0.90% w/w salidroside based on the total weight of the herbal extract.

[00403] One bioactive ingredient of interest in Rhodiola crenulata is salidroside. Rosavins is another bioactive constituent identified from the plant. Salidroside and/or rosavins can be used as references for determination of the quality of the preparations. In some embodiments, a composition of the disclosure comprises an herbal extract of Rhodiola crenulata containing a desired amount of about 0.01%, about 0.05%, about 0.10%, about 0.15%, about 0.20%, about 0.25%, about 0.30%, about 0.35%, about 0.40%, about 0.45%, about 0.50%, about 0.60%, about 0.70%, about 0.80%, about 0.90%, about 1%, about 1.25%, about 1.50%, about 2%, about 3%, about 3%, or about 5% or more salidroside w/w of the total weight of the extract. In some embodiments, compositions of the present disclosure comprise an extract of Rhodiola crenulata comprising 1-5% salidroside w/w of the total weight of the extract. In some embodiments, the extracts comprise 2-5% salidroside, and in another embodiment, the extracts comprise 3-5% salidroside w/w of the total weight of the extract. In some embodiments, the compositions of the present disclosure comprise an herbal extract of Rhodiola crenulata comprising about 1%, about 2%, about 5%, about 10%, about 15%, about 20%, about 25% or more of the total weight of the composition. In still further embodiments, these formulations contain 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0 or more mg of salidroside derived from Rhodiola crenulata. In still further embodiments, these formulations contain 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4% or 1.5% salidroside.

[00404] In one or more embodiments, the citrulline comprises L-citrulline, L-citrulline DL- malate or mixtures thereof. In one or more embodiments, the citrulline comprises L-citrulline DL-malate 2: 1, which combines two parts L-citrulline, a non-essential amino acid, with one part DL-malic acid, a racemic mixture of dicarboxylic acids.

[00405] In another embodiment, the composition comprises one or more additional active ingredients selected from the group consisting of a catechin and an extract comprising a catechin. In one or more embodiments, the composition comprises from about 250 to 800 mg, from about 300 to 700 mg, from about 350-6500 mg and from about 400-600 mg of catechin extract.

[00406] The four types of catechins (or epicatechins) found in green tea (from Camellia sinensis ) are the epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin gallate (ECG), and epicatechin (EC). EGCG accounts for about 50-80% of the catechins in green tea. Catechins may also be found from other sources such as cocoa.

[00407] In one or more embodiments, the composition comprises an extract from Camellia sinensis or a green tea containing a catechin selected from the group consisting of epigallocatechin gallate, epigallocatechin, epicatechin gallate, epicatechin and combinations thereof, in varying concentrations.

[00408] The catechin can be, but is not limited to, catechin monomers (e.g., flavan-3-ol monomers), catechin isomers, and combinations thereof. Some embodiments comprise catechin esters, such as catechin gallate (CG), gallocatechin (GC), gallocatechin gallate (GCG), epicatechin (EC), epicatechin gallate (ECG), epigallocatechin (EGC), and epigallocatechin gallate (EGCG), and combinations of two or more thereof.

[00409] Catechins can be derived from a variety of sources, such as tea plants (e.g., Camellia sinensis), cocoas (e.g., made from seeds of Theobroma cacao), and chocolates. In some embodiments, the catechins are extracted from a plant, such as a green tea plant (e.g., Camellia sinensis).

[00410] Some embodiments comprise a plant extract that comprises catechins. In some embodiments, the plant extract comprises more than about 70% (w/w) catechins, more than about 80% (w/w) catechins, more than about 90% (w/w) catechins, or more than about 95% (w/w) catechins. In some embodiments, the plant extract comprises more than 70% (w/w) catechins, more than 80% (w/w) catechins, more than 90% (w/w) catechins, or more than 95% (w/w) catechins.

[00411] In some embodiments, the plant extract is a green tea extract. The extract can be of any suitable green tea variety, such as sencha, fukushami sencha, gyokuro, kabusecha, matcha, tencha, genmaicha, hojicha, shincha, ichibancha, nibancha, or sanbancha. [00412] In some embodiments, the composition comprises from about 250 mg to about 1,500 mg green tea extract comprising at least 20, 30, 40, 50, 60, 70, 80, or 90% (w/w) catechins.

[00413] In one or more embodiments, the composition comprises as an active ingredient a green tea extract containing (-)-gallocatechin gallate (GCG) at 5 to 25% by weight based on a total weight of the composition or the extract and (-)-epigallocatechin gallate (EGCG) at 7 to 15% by weight based on the total weight of the composition or the extract.

[00414] In one example, the citrulline, glutathione and ornithine in the composition, can include glutathione, L-citrulline and ornithine, or a combination thereof. In one example, the glutathione, L-citrulline and ornithine can comprise from about 40 wt % to about 98 wt % of the composition. In another example, the glutathione, L-citrulline and ornithine can comprise from 10 wt % to 60 wt % of the composition.

[00415] In one or more embodiments, the composition comprises at least the active ingredients citicoline, citrulline, and glutathione, catechins and one or more additional active ingredients selected from the group consisting of lipophilic nutrients and vitamins, in varying concentrations.

[00416] In one or more embodiments, the lipophilic nutrient is selected from the group consisting of lutein, zeaxanthin, astaxanthin, beta-carotene, lycopene, Vitamin A, Vitamin D, Vitamin E, Vitamin K, Coenzyme Q10, linoleic acid, alpha linolenic acid, arachidonic acid, docosahexaenoic acid, eicosapentaenoic acid, and combinations thereof.

[00417] In one or more embodiments, the lipophilic nutrient is lycopene. Lycopene is a natural pigment found in ripe fruit, particularly in tomato, or synthesized, especially from a fungus, Blakeslea trispora. It belongs to the carotenoid family and its structure is similar to that of .beta. -carotene. The lycopene content, in a food supplement in accordance with the invention, may be between 0.1% and 30% by weight, especially between 0.1% and 20% by weight, and particularly between 0.1% and 10% by weight, relative to the total weight of the combination of active agents. In one or more embodiments, the lycopene is provided in a range selected from: 5 to 90 mg; 10 to 85 mg; 15 to 80 mg; 20 to 80 mg; 20 to 70 mg; or 20 to 40 mg.

[00418] In another example, the L-citrulline can be present in the composition from about 1 wt % to about 80 wt %. In another example, the L-citrulline can be present in the composition from about 0.5 wt % to about 90 wt %. In yet another example, the L-citrulline can be present in the composition from about 0.25 wt % to about 95 wt %. In a further example, the L-citrulline can be present in the composition from about 0.125 wt % to about 99 wt %. In yet a further example, the L-citrulline can be present in the composition from about 0.1 wt % to about 5 wt %. In yet another example, the L-citrulline can be present from about 0.5 wt % to about 2.5 wt %.

[00419] In yet another example, the citrulline in the composition can include a combination of L-malate and L-citrulline. In one example, the L-malate can range from about 1 wt % to about 80 wt % and the L-citrulline can range from about 1 wt % to about 80 wt %. In another example, the L-malate can range from about 0.5 wt % to about 90 wt % in and the L-citrulline can range from about 0.5 wt % to about 90 wt %. In yet another example, the L-malate can range from about 0.25 wt % to about 95 wt % and the L-citrulline can range from about 0.25 wt % to about 95 wt %. In yet a further example, the L-malate can range from about 40 wt % to about 95 wt % and the L-citrulline can range from about 0.1 wt % to about 5 wt %.

[00420] The ratio of the weight percentage of L-malate and L-citrulline can also vary. In one embodiment, the L-malate and L-citrulline can be present in the composition at a weight percent concentration ranging from about 1 :5 to about 5: 1, respectively. In another embodiment, the L-malate and L-citrulline can be present in the composition at a weight percent concentration ranging from about 1 : 1 to about 5: 1, respectively. In yet another embodiment, the L-malate and L-citrulline can be present in the composition at a weight percent concentration of about 2: 1, respectively.

[00421] In one or more embodiments, the source of nitric oxide can be in the composition at a range from about 1 wt % to about 80 wt %. In another example, the source of nitric oxide can be in the composition at a range from about 0.01 wt % to about 90 wt %. In another example, the source of nitric oxide can be present in the composition from about 15 wt % to about 30 wt %.

[00422] In one or more embodiments, the source of nitric oxide can include beet root extract, vitamin Bl, or a combination thereof. In another example, the source of nitric oxide can include the beet root extract and the vitamin B 1. In one example, including beet root extract and vitamin B 1 , the beet root extract can range from about 5 wt % to about 90 wt % and the vitamin B 1 can range from about 0.01 wt % to about 80 wt % of the composition. In another example, including beet root extract and vitamin Bl, the beet root extract can range from about 1 wt % to about 95 wt % and the vitamin B 1 can range from about 0.005 wt % to about 99 wt % of the composition. In yet another example, including beet root extract and vitamin Bl, the beet root extract can range from about 0.1 wt % to about 99 wt % and the vitamin Bl can range from about 0.0025 wt % to about 0.995 wt % of the composition. In a further example, the beet root extract can range from about 15 wt % to about 30 wt % and the vitamin Bl can range from about 0.5 wt % to about 5 wt %. [00423] In one example, the composition can include a myeloperoxidase inhibitor can be pomegranate fruit extract, red grape polyphenols, apple extract, blueberry extract, capsicum extract, grape extract, green tea extract, olive extract, bergamot extract, mangosteen extract, mangosteen fruit, or a combination thereof. In one example, the myeloperoxidase inhibitor can range from about 1 wt % to about 90 wt %. In another example, the myeloperoxidase inhibitor can range from about 0.5 wt % to about 95 wt %. In yet another example, the myeloperoxidase inhibitor can range from about 0.25 wt % to about 99 wt %. In another example, the myeloperoxidase inhibitor can range from about 1 wt % to about 15 wt %. In yet a further example, the myeloperoxidase inhibitor can range from about 3 wt % to about 12 wt %.

[00424] In one example, the myeloperoxidase inhibitor can include pomegranate fruit extract, red grape polyphenols, or a combination thereof. In another example, of the composition, the myeloperoxidase inhibitor can include pomegranate fruit extract and red grape polyphenols. In one example, the pomegranate fruit extract can range from about 1 wt % to about 80 wt % and the red grape polyphenols can range from about 1 wt % to about 80 wt % of the composition. In another example, the pomegranate fruit extract can range from about 0.5 wt % to about 90 wt % and the red grape polyphenols can range from about 0.5 wt % to about 90 wt % of the composition. In yet another example, the pomegranate fruit extract can range from about 0.25 wt % to about 95 wt % and the red grape polyphenols can range from about 0.25 wt % to about 95 wt % of the composition. In one example, the pomegranate fruit extract can range from about 0.25 wt % to about 10 wt % and the red grape polyphenols can range from about 0.01 wt % to about 2 wt % of the composition.

[00425] In one or more embodiments, the composition can include apple extract, grape extract, green tea extract, and olive extract. In one example, the apple extract, the grape extract, the green tea extract, and the olive extract collectively can range from about 1 wt % to about 80 wt % of the composition. In another example, the apple extract can range from about 0.01 wt % to about 80 wt %, the grape extract can range from about 0.01 wt % to about 80 wt %, the green tea extract can range from about 0.01 wt % to about 80 wt %, and the olive extract can range from about 0.01 wt % to about 80 wt % of the claimed composition. In yet another example, the apple extract can range from about 0.01 wt % to about 5 wt %, the grape extract can range from about 0.01 wt % to about 7 wt %, the green tea extract can range from about 0 wt % to about 1 wt %, and the olive extract can range from about 0 wt % to about 1 wt % of the claimed composition. In another example, the apple extract, the grape extract, the green tea extract, and the green tea leaf extract, are each present in the composition from about 0.01 wt % to about 1 wt %. [00426] In one or more embodiments, the apple extract can comprise an extract derived from a member selected from the group consisting of Malus domestica, Malus sieversii, Malus sylvestris, Malus pumila, and combinations thereof. In one example, the grape extract can comprise a member selected from the group consisting of Vitis vinifera, Vitis labrusca, Vitis riparia, Vitis rotundifolia, Vitis rupestris, Vitis aestivalis, Vitis mustangensis, and combinations thereof. In one example, the grape extract can be derived from Vitis vinifera.

[00427] In one or more embodiments, the green tea extract can be derived from Camellia sinensis. In some embodiments, the green tea extract can comprise any or all parts of the tea including but not limited to the leaf, seed, stem, flower, or combination thereof. In one embodiment, the green tea extract can be derived from the leaves. In another example, the extract solvent can be water, ethanol, ethyl acetate, or combinations thereof.

[00428] In one or more embodiments, the olive extract comprises a subspecies of Olea europea selected from the group consisting of the subspecies europea, cuspidiata, guanchica, cerasiformis, maroccana, laperrinei, cerasiformis, or a combination thereof. In some embodiments, the olive extract can comprise any or all parts of the olive including but not limited to the leaf, seed, pulp, fruit, stem, or combination thereof. In one embodiment, the olive extract can be derived from the leaves. In another example, the extraction solvent can be an ethanol and water solution.

[00429] The amount of the myeloperoxidase inhibitor can also vary. In one example, the blueberry fruit extract can range from about 0.01 wt % to about 80 wt %, the capsicum fruit extract can range from about 0.01 wt % to about 80 wt %, and the turmeric root extract can range from about 0.01 wt % to about 80 wt % of the composition. In another example, the blueberry fruit extract can range from about 0.005 wt % to about 90 wt %, the capsicum fruit extract can range from about 0.005 wt % to about 90 wt %, and the turmeric root extract can range from about 0.005 wt % to about 90 wt % of the composition. In yet another example, the blueberry fruit extract, the capsicum fruit extract, and the turmeric root extract can each range from about 0.005 wt % to about 5 wt % of the composition. In a further example, the blueberry fruit extract, the capsicum fruit extract, and the turmeric root extract can each range from about 0.1 wt % to about 2.5 wt % of the composition.

[00430] In some examples, the composition can further include d-ribose, folic acid, malic acid, vitamin B6, vitamin B 12, vitamin D3, magnesium oxide, calcium, inulin, chicory root extract, cherry extract, or a combination thereof. In some examples, the composition can further include a pharmaceutically acceptable carrier. In one example, the composition can further include coatings, isotonic agents, absorption delaying agents, binders, adhesives, lubricants, disintegrants, coloring agents, flavoring agents, sweetening agents, absorbents, detergents, emulsifying agents, antioxidants, vitamins, minerals, proteins, fats, carbohydrates, or a combination thereof. In one example, the composition can further include a sweetener, a preservative, a flavoring, or a combination thereof. In some examples, the formulation can include a polymers for sustained release of a given compound.

[00431] In another example, the formulation can include emulsifiers. In one example, the emulsifier can add stability to the final product. Examples of suitable emulsifiers include, but are not limited to, lecithin (e.g., from egg or soy), or mono- and di-glycerides. Other emulsifiers are readily apparent to the skilled artisan and selection of suitable emulsifier(s) will depend, in part, upon the formulation and final product.

[00432] In yet another example, the formulation can include a preservative. In one example, the preservatives such as potassium sorbate, sodium sorbate, potassium benzoate, sodium benzoate, or calcium disodium EDTA are used.

[00433] In a further example, the nutritional supplement can contain natural or artificial sweeteners, e.g., glucose, sucrose, fructose, saccharides, cyclamates, aspartame, sucralose, aspartame, acesulfame K, or sorbitol.

[00434] In one example, the composition can be in the form of an oral dosage formulation. In another example, the oral dosage formulation can be a capsule, a tablet, a soft gel, a lozenge, a sachet, a powder, a beverage, a syrup, a suspension, or a food. In another example, the compositions can be formulated into a food or drink, and provided, for example, as a snack bar, a cereal, a drink, a gum, or in any other easily ingested form. In one example, the composition can be incorporated into a liquid beverage such as water, milk, juice, or soda. In another example, the composition can be formulated into a nutritional beverage. The nutritional beverage can be in a premixed formulation or can be a powdered mix in that can be added to a beverage. In another example, the powder mix in can be in the form of granules. In one example, the composition can be dried and made readily soluble in water.

[00435] In yet another example, the oral dosage form can be in a solution or a suspension in an aqueous liquid or non-aqueous liquid, such as ethanol, glycerol, vegetable oil, salt solutions, or hydroxymethyl cellulose; or in the form of an oil-in-water emulsion or a water-in-oil emulsion, or a combination thereof. In examples where the oral dosage form includes oils, the oils can be edible oils, such as e.g. cottonseed oil, sesame oil, coconut oil, or peanut oil. In some examples, the composition can include suitable dispersing or suspending agents for aqueous suspensions include synthetic or natural gums such as tragacanth, alginate, gum arabic, dextran, sodium carboxymethylcellulose, gelatin, methylcellulose, and polyvinylpyrrolidone. [00436] In another example, the composition can be formulated into a food product. In one example, the food product can be a pudding, confections, (i.e., candy), ice cream, frozen confections and novelties, or non-baked extruded food products such as bars. In one example, the composition can be a powder that is added to non-baked goods. For, example a nutritional bar can be manufactured by adding the powder to the dry ingredients and then incorporating the dry and wet. The wet and dry ingredients can be mixed until the dough phase is reached. The dough can then be put into an extruder and extruded; the extruded dough can be cut into appropriate lengths; and the product can be cooled.

[00437] Flavors, coloring agents, spices, nuts, and the like can be incorporated into the product. Flavorings can be in the form of flavored extracts, volatile oils, chocolate flavorings (e.g., non-caffeinated cocoa or chocolate, chocolate substitutes such as carob), peanut butter flavoring, cookie crumbs, crisp rice, vanilla, or any commercially available flavoring. Flavorings can be protected with mixed tocopherols. Examples of useful flavorings include but are not limited to pure anise extract, imitation banana extract, imitation cherry extract, chocolate extract, pure lemon extract, pure orange extract, pure peppermint extract, imitation pineapple extract, imitation rum extract, imitation strawberry extract, or pure vanilla extract; or volatile oils, such as balm oil, bay oil, bergamot oil, cedarwood oil, cherry oil, walnut oil, cinnamon oil, clove oil, or peppermint oil; peanut butter, chocolate flavoring, vanilla cookie crumb, butterscotch, or toffee. In one example, the nutritional supplement contains berry or other fruit flavor. The food compositions may further be coated, for example with a yogurt coating if it is as a bar.

[00438] In one example, the formulation can be in the form of a cream or lotion for topical application. In another example the active ingredient can be in the form of a bolus, electuary, or paste. In yet another example, the composition can be formulated as a depot preparation. In one example, the depot can be for implantation (e.g. subcutaneously, intra-abdominally, or intramuscularly) or intramuscular injection. In one example, the formulation can be formulated as an ion exchange resin.

[00439] In one example, the composition can provide an acute increase in biosynthesis of nitric oxide and/or inhibit the activity of myeloperoxidase. In another example, the composition can acutely raise nitric oxide levels in the subject by enhancing biosynthesis production of nitric oxide. In yet another example, the composition can acutely raise nitric oxide levels in the subject by inhibiting myeloperoxidase activity. In a further example, the composition can acutely raise nitric oxide levels in the subject by providing a nitrite/nitrate source for conversion to nitric oxide. [00440] Further presented herein, is a method for acutely raising nitric oxide levels in a subject. In one example, the method can include administering to the subject a therapeutically effective amount of any of the compositions previously presented or within the examples section.

[00441] In another example, a method of treating a subject for a condition or disorder that is response to nitric oxide therapy is presented. In one example, the method can include: acutely raising nitric oxide levels in a subject by simultaneously increasing biosynthesis of nitric oxide, increasing nitrate/nitrite levels, and inhibiting myeloperoxidase activity. In one example, the method can include administering a therapeutically effective amount of the compositions above.

[00442] The nitric oxide increasing formulations described herein may be manufactured and sold in a variety of forms. In some embodiments, they may be manufactured and sold as a single strength beverage for direct consumption by the consumer. In other embodiments, the formulations may be sold in an aqueous concentrate to be diluted with water to yield a beverage that treats or prevents low levels of nitric oxide, symptoms of low levels of nitric oxide, and conditions caused by or exacerbated by low levels of nitric oxide. In one or more embodiments, the formulations provided here may be provided as a powder, granule formation, or tablet which is to be mixed with other food substances to yield a nutritional food product that treats or prevents low levels of nitric oxide, symptoms of low levels of nitric oxide, and conditions caused or exacerbated by low levels of nitric oxide. In one or more embodiments, the formulations may be provided as a powder, granule formation, or tablet which is to be dissolved in water to yield a beverage that treats or prevents low levels of nitric oxide, symptoms of low levels of nitric oxide, and conditions caused or exacerbated by low levels of nitric oxide.

[00443] Mammalian subjects amenable for treatment according to the formulations and methods of the invention further include, but are not limited to, human and other mammalian subjects at risk for or with symptoms of low levels of nitric oxide, as well as symptoms or conditions associated with or complicated by low levels of nitric oxide. Low levels of nitric oxide may be caused by any of a variety of reasons including, but not limited to, intense exercise, illness, stress, diet, exposure to toxins, and poor sleeping habits.

[00444] Compositions and methods described herein are useful for optimizing health and performance; preventing illness; decreasing recovery times from exertion, illness, and injury; increasing energy levels; improving exercise performance; improving hydration; preventing muscle damage after exercise; and increasing stamina during exercise. They are additionally useful for treating, preventing or alleviating symptoms of low levels of nitric oxide, including, but not limited to, extreme tenderness in the joint, inflammation, swelling, pain, redness in the affected area, confusion, lethargy, rapid breathing, shortness of breath, wheezing, chest pain or pressure, joint stiffness, swelling, joint deformity, crepitus, non-specific fever, joint inflammation, headaches, fatigue, a feeling of euphoria and nausea, seizures, coma, generalized weakness, abnormal heart function, decreased platelet count, areas of mottled skin, fever, low blood pressure, tachycardia, skin discoloration, irregular heartbeat, loss of appetite, jaundice, abdominal pain, easy bruising, vomiting, ascites, easy bruising, dry skin, dry mouth, low blood pressure, frequent urination, chest pain, lymph node pain, night sweats, skin rash, hyperventilation, constipation, severe anemia, memory loss, mood swings, musculoskeletal pain and light headedness.

[00445] In one or more embodiments, the formulations provided here may further comprise vitamins and antioxidants. Antioxidants may be used in the reduction of reactive oxygen species in vertebrates, including mammals. Reduction of free radicals and other reactive oxygen species (ROS) is effective in the treatment of diseases including, but not limited to, gout, abdominal pain, Alzheimer's disease, amyotrophic lateral sclerosis, arthritis, atherosclerosis, cancer, cardiovascular disease, cataracts, cellulitis and pancreatic impairment, chronic obstructive pulmonary disease, coronary artery disease, diabetes, diabetic ketoacidosis, ethanol toxicity, exercise fatigue, folliculitis, gout, heart failure, hemochromatosis, hemorrhage, hepatic disease, hepatitis C, hypertension, hyperventilation, hypotension, hypoxia, hypoperfusion, infection, inflammatory bowel disease, irregular heart rhythm, Lesch- Nyhan syndrome, lethargy, macular degeneration, methicillin resistant staphylococcus aureus (MRSA) fibromyalgia, multiple sclerosis, nausea, non-Hodgkin's and Burkitfs lymphoma, Parkinson's disease, psoriasis, regional hypoperfusion, pancreatic impairment, reperfusion injury, respiratory disease, Reynaud's phenomenon, sepsis, severe anemia, shock, tachycardia, vomiting and weight gain.

[00446] Formulations and methods herein employ the compositions alone or with one or more additional agents to optimize health and performance; prevent illness; decrease recovery times from exertion, illness and injury; and extend endurance during exercise. Useful secondary or additional agents for use within the formulations and methods of the present invention include, but are not limited to, adaptogens, alkalinity increasing agents, amino acids and amino acid derivatives, anti-inflammatory agents, anti-nausea agents, analgesics, antioxidants, aphrodisiacs, detoxifying agents, dietary supplements, herbal supplements, calming agents, herbs and plant extracts, flavorings, essential nutrients, coenzymes, electrolytes, energy boosters, essential trace elements, flavonoids, hormones, immune boosters, neurotransmitters, essential fatty acids, memory enhancers, vitamins and minerals, protein, sedatives, stimulants and nutritional supplements for use within the formulations and methods described herein. Within these formulations and methods, the secondary agent may be provided in any of a variety of forms, including any polymorphs, enantiomers, pharmaceutically acceptable salts, solvates, hydrates, or combinations thereof. Such combinations of a composition and secondary agent may be administered either combinatorially or coordinately as disclosed herein to effectively optimize health and performance; prevent illness; decrease recovery times from exertion, illness, and injury; increase energy levels; improve exercise performance; improve hydration; prevent muscle damage after exercise; and increase stamina during exercise.

[00447] Formulations and methods as described herein may include adaptogens. An adaptogen is a metabolic regulator which increases the ability of an organism to adapt to environmental factors, and prevents damage from such factors. Exemplary adaptogens include, but are not limited to, ashwagandha, eleutherococcus senticosus, reishi, astragalus, licorice root, panax quinquefolius, panax ginseng and schisandra berries.

[00448] Antioxidants included in the formulations provided herein may be in the form of nutritional supplements such as, but not limited to, vitamin A, vitamin C, vitamin erythorbic acid, beta-carotene, carotenes, lutein, manganese, lycopene, melatonin, or coenzyme Q10 or may be present in plant extracts, either of which may be combined with the nitric oxide increasing formulations of the present invention. Plant extracts containing antioxidants may come from plant sources such as, but not limited to, apricot, acai fruit, acerola, apple, blueberry, blackberry, black currant, carrots, cherry, chokeberry, cranberry, elderberry, green tea, goji berry, grape seed, mangosteen, maqui berry, milk thistle, pomegranate seed, prune, raspberry, red grape, rooibos, rosehips, strawberry, seabuckthorn, while grape, whole grape, yumberry and acerola fruit.

[00449] Formulations and methods herein may further employ vitamin, mineral and nutritional supplements in a variety of forms including, but not limited to, vitamin B complex, folic acid, niacin, niacinamide, pantothenic acid, pyridoxine HCL, vitamin B2, folate, biotin, vitamin C, vitamin D, vitamin D3, vitamin E, vitamin K, cyanocobalamin, inositol, thiamine, thiamine mononitrate, calcium pantothenate, mixed tocophyerols, d-alpha tocopheryl acetate, magnesium, calcium, calcium carbonate, calcium chelate, calcium di-phosphate, calcium phosphate, iron, magnesium carbonate, magnesium citrate, magnesium oxide, magnesium phosphate, manganese chelate, manganese sulfate, potassium, potassium chelate, potassium chloride, sodium, zinc, vanadyl sulphate, chromium, chromium chloride, chromium picolinate, and chromium polynicotinate. The amount of vitamin, mineral and nutritional supplements may vary in the formulations and methods described herein.

[00450] In some embodiments, the formulations may comprise independently between about 1% and to about 250% of the U.S. recommended daily allowance, about 10% to about 250%, about 10% and 150%, between about 10% to about 100%, about 10% to about 50% of the U.S. recommended daily allowance of any one vitamin, mineral or nutritional supplement. In some embodiments the composition as described herein has between 10% to 250%, about 10% to about 150%, about 25% to about 100%, about 50% to about 75% of the U.S. recommended daily amount of vitamin B3 or vitamin B complex.

[00451] In some embodiments, the compositions and methods described herein may further include amino acids, amino acid precursors, and amino acid derivatives whether branched or straight chain amino acids. Exemplary amino acids, precursors and derivatives which may be used in the formulations and methods described herein include, but are not limited to, 5-HTP, arginine, beta alanine, carnitine fumarate, citrulline malate, glutamine peptide, glycine, 1- alanine, 1-arginine, 1-arginine hydrochloride, 1-histidine, 1-methionine, 1-lysine HC1, 1- phenylalanine, leucine ethyl ester, 1-glutamine, 1-isoleucine, 1-theanine, 1-tyrosine, phenylalanine, taurine, tri-methyl glycine, tryptophan, tyrosine, 1-carnitine, 1-carnosine, glutamine alpha ketoglutarate and alpha-L-polylactate.

[00452] During exercise and illness, dehydration and electrolyte balance can be an issue leading to muscle cramps, loss of appetite, dizziness, irregular heartbeat, muscle weakness, confusion, nausea, and muscle spasms. The compositions and methods described herein may therefore include electrolytes to maintain homeostasis. Electrolytes used herein include, but are not limited to, sodium chloride, sodium acetate, acidic sodium citrate, acidic sodium phosphate, sodium chloride, sodium bicarbonate, sodium bromide, sodium citrate, sodium lactate, sodium molybdate, sodium phosphate, anhydrous sodium sulphate, sodium sulphate, sodium tartrate, sodium benzoate, sodium selenite, and other sodium salts and mixtures thereof; potassium chloride, potassium acetate, potassium bicarbonate, potassium bromide, potassium citrate, potassium-D-gluconate, monobasic potassium phosphate, potassium tartrate, potassium sorbate, potassium iodide, and other potassium salts and mixtures thereof; magnesium carbonate, magnesium citrate, magnesium oxide, magnesium phosphate, as well as other magnesium salts and mixtures thereof; calcium chloride, calcium carbonate, calcium chelate, calcium di-phosphate, calcium lactate, calcium phosphate tribasic and other calcium salts and mixtures thereof. Such electrolytes may be included in the formulations described herein in proportions and amounts suitable to replenish salts lost during exercise or illness or otherwise depleted.

[00453] Additional agents which may be used in the compositions and methods described herein include anti-inflammatory agents including, but not limited to, extracts from plants such as maqui berry, milk thistle, skull cap, red raspberry, red sour cherry, green tea and hops.

[00454] Other agents which may be used in the compositions and methods described herein include anti-nausea agents including, but not limited to, extracts from peppermint, ginger and chamomile.

[00455] A further agent which may be used in the compositions and methods described herein includes analgesic agents such as, but not limited to, white willow bark.

[00456] The formulations and methods described herein may additionally include herbal supplements and extracts with beneficial properties including, but not limited to, passion flower, horny goat weed, skullcap, milk thistle, Echinacea, dandelion leaf, St. John's wort, green tea, black tea, chamomile or peppermint, or an extract thereof.

[00457] The formulations and methods described herein may further include plants with beneficial properties including, but not limited to, guarana seeds, acerola berries, coconut water, yerba mate, acai berry, ginseng root, panax ginseng root, ginkgo biloba, white willow bark, acacia, ashwagandha, chokeberry, elderberry, cranberry, maqui berry, blueberry, pomegranate, rooibos, goji berry, elder berry, valerian, seabuckthorn, yumberry, blackberry, astragalus, damiana, and ginger.

[00458] The compositions and methods described herein may further include energy boosters that may increase performance including, but not limited to, creatine ethyl ester, creatine monohydrate, magnesium creatine chelate, creatine hydrochloride, creatine nitrate, creatine monohydrate and royal jelly.

[00459] The compositions and methods described herein may further include flavonoids. Useful flavonoids within the compositions and methods of the present invention are present in chamomile extract, cocoa powder, red grape, black tea, and white tea, ginkgo biloba, berries, parsley, and green tea some or all of which may be included in the compositions and methods described herein.

[00460] The formulations and methods described herein may further include stimulants. Such stimulants include, but are not limited to, caffeine, citicoline, d-glucuronolactone, guarana extract, ginseng, concentrated green tea, green coffee beans, glucuronolactone, guarana, panax ginseng, panax quinquefolius, Siberian ginseng, and theobromine. [00461] Additional agents which may be included in the formulations and methods described herein are immune boosters including, but not limited to, Echinacea and astragalus root.

[00462] The compositions herein may additionally comprise one or more flavoring agents. Such flavorings are any flavoring typically included in a beverage composition including, but not limited to synthetic flavorings, fruit juice, vegetable juice, milk solids, fruit flavors, herbal flavor and mixtures thereof. The fruit juice can be any citrus juice, non-citrus juice, or mixture thereof, which is known for use in dilute juice beverages. The juice can be extracted from, but riot limited to, apple, cranberry, pear, peach, plum, apricot, nectarine, grape, guava, cherry, currant, raspberry, gooseberry, elderberry, blackberry, blueberry, strawberry, lemon, lime, mandarin, orange, tomato, lettuce, dandelion, rhubarb, pineapple, coconut, pomegranate, kiwi, mango, papaya, banana, watermelon, passion fruit, tangerine, and cantaloupe. The vegetable juice can be any vegetable juice generally consumed including, but not limited to, celery, spinach, cabbage, watercress, carrot, beet, spirulina, sweet potato, kale, romaine, collard greens, endive, escarole, bok choy, fennel, parsley, wheat grass, or cucumber. Such fruit and vegetable juices may or may not have additional beneficial properties such as antioxidants and/or flavonoids.

[00463] Formulations and methods herein may additionally include a protein source. Protein sources include, but are not limited to, milk solids, calcium caseinate, whey protein concentrate, whey protein isolate, whey protein hydrolysate, soy protein, casein hydrolysate, rice protein, wheat protein, corn protein, partially hydrolyzed whey protein, or ultra-filtered whey protein. In various embodiments, the protein source may comprise vegetable proteins such as soybean meal, soy protein concentrate, corn gluten meal, wheat gluten, cottonseed, and peanut meal, or animal proteins such as casein, albumin, and meat protein. Examples of meat protein useful herein include pork, lamb, equine, poultry, fish, and mixtures thereof. In various embodiments, the compositions comprise from about 5% to about 50% crude protein.

[00464] Formulations and methods herein may further include one or more sweeteners or carbohydrate source. Sweeteners which may be used in the formulations herein include, but are not limited to, acesulfame potassium, aspartame, cane sugar, beet sugar, corn syrup, crystalline fructose, dextrose, D-ribose, fructose, glucose, glucose-fructose syrup, high fructose corn syrup, high fructose liquid sugar, honey, maltodextrin, sorbitol, stevia, sucralose, sucrose, sugar, trehalose, truvia or xylitol.

[00465] A broad range of mammalian subjects, including human subjects, are amenable for treatment using the formulations and methods of the invention. The compositions and methods described herein are particularly useful for optimizing health and performance; preventing illness; decreasing recovery times from exertion, illness, and injury; increasing energy levels; improving exercise performance; improving hydration; preventing muscle damage after exercise; and increasing stamina during exercise. The formulations described herein may be used prophylactically or therapeutically.

[00466] The amount, timing and mode of delivery of compositions of the invention comprising an effective amount of a nitric oxide increasing formulation of the present invention will be routinely adjusted on an individual basis, depending on such factors as weight, age, gender, and condition of the individual, the severity of the symptoms, whether the administration is prophylactic or therapeutic, and on the basis of other factors known to effect drug delivery, absorption, pharmacokinetics, including, but not limited to, half-life, and efficacy.

[00467] An effective dose or multi-dose treatment regimen for the instant nitric oxide increasing formulations will ordinarily be selected to approximate a minimal dosing regimen that is necessary and sufficient to substantially prevent or alleviate low levels of nitric oxide and related conditions in the subject. A dosage and administration protocol will often include repeated dosing therapy over a course of several days or even one or more weeks, months, or years, An effective treatment regime may also involve prophylactic dosage administered on a day or multi-dose per day basis lasting over the course of days, weeks, months or even years.

[00468] The compositions of the present invention may be administered by any means that achieves the intended therapeutic or prophylactic purpose. Suitable routes of administration for nitric oxide increasing antioxidant compositions of the invention comprising solutions include, but are not limited to, oral, buccal, nasal, aerosol, mucosal, injectable, slow release, controlled release, iontophoresis, sonophoresis, and other conventional delivery routes, devices and methods.

[00469] Within additional aspects of the invention, combinatorial formulations and coordinate administration methods are provided which employ an effective amount of the compositions, and one or more additional active agent(s) that is/are combinatorially formulated or coordinately administered.

[00470] Such secondary or additional agents for use within the formulations and methods of the present invention include, but are not limited to, adaptogens, amino acids and amino acid derivatives, anti-inflammatory agents, anti-nausea agents, analgesics, antioxidants, aphrodisiacs, detoxifying agents, dietary supplements, herbal supplements, calming agents, herbs and plant extracts, flavorings, essential nutrients, coenzymes, electrolytes, energy boosters, essential trace elements, flavonoids, hormones, immune boosters, neurotransmitters, essential fatty acids, memory enhancers, vitamins and minerals, protein, sedatives, stimulants and nutritional supplements for use within the formulations and methods described herein.

[00471] Such combinations may be administered either combinatorially or coordinately as disclosed herein to effectively optimize health and performance; prevent illness; decrease recovery times from exertion, illness, and injury; increase energy levels; improve exercise performance; improve hydration; prevent muscle damage after exercise; and increase stamina during exercise.

[00472] Adaptogen agents for use within the formulations and methods herein include, but are not limited to, ashwagandha, eleutherococcus senticosus, reishi, astragalus, licorice root, panax quinquefolius, panax ginseng and schisandra berries.

[00473] Antioxidants included in the formulations provided herein may be in the form of nutritional supplements such as, but not limited to, vitamin A; vitamin C; vitamin E; erythorbic acid; beta-carotene; carotenes; lutein; manganese; lycopene; melatonin; or coenzyme Q10; xanthine oxidase inhibitors, including, but not limited to, allopurinol and folic acid; NADPH oxidase inhibitors, including, but not limited to, adenosine; calcium channel blockers; superoxide dismutases; catalases; albumin; inhibitors of iron redox cycling, including, but not limited to deferoxamine, apotransferin and ceruloplasmin; beta carotene; ascorbates; myricetin-3-O-galactoside, quercitin-3-O-galactoside; alpha tocopherol; and benzaldehyde derivatives, such as those described in U.S. patent application Ser. No. 12/418,342, incorporated by reference herein in its entirety. In some embodiments, antioxidants may be present in plant extracts which may also be combined with the nitric oxide increasing formulations. Plant extracts may come from plant sources such as, but not limited to, apricot, acai fruit, acerola, apple, blueberry, blackberry, black currant, carrots, cherry, chokeberry, cranberry, elderberry, green tea, goji berry, grape seed, mangosteen, maqui berry, milk thistle, pomegranate seed, prune, raspberry, red grape, rooibos, rosehips, strawberry, seabuckthorn, white grape, whole grape, yumberry and acerola fruit.

[00474] Vitamin, mineral and nutritional supplements for use herein may be in a variety of forms including, but not limited to, vitamin B complex, folic acid, niacin, niacinamide, pantothenic acid, pyridoxine HC1, vitamin B2, folate, biotin, vitamin C, vitamin D, vitamin D3, vitamin E, vitamin K, cyanocobalamin, inositol, thiamine, thiamine mononitrate, calcium pantothenate, mixed tocophyerols, d-alpha tocopheryl acetate, magnesium, calcium, calcium carbonate, calcium chelate, calcium di-phosphate, calcium phosphate, iron, magnesium carbonate, magnesium citrate, magnesium oxide, magnesium phosphate, manganese chelate, manganese sulfate, potassium, potassium chelate, potassium chloride, sodium, zinc, vanadyl sulphate, chromium, chromium chloride, chromium picolinate, and chromium polynicotinate.

[00475] Amino acids, amino acid precursors and derivatives as used within the formulations herein may be branched or straight chain amino acids. Exemplary amino acids, precursors and derivatives which may be used in the formulations and methods described herein include, but are not limited to, 5-HTTP, arginine, beta alanine, carnitine fumarate, citrulline malate, glutamine peptide, glycine, 1-alanine, 1-arginine, 1-arginine hydrochloride, 1-histidine, 1- methionine, 1-lysine HC1, 1-phenylalanine, leucine ethyl ester, 1-glutamine, 1-isoleucine, 1- theanine, 1-tyrosine, phenylalanine, taurine, tri-methyl glycine, tryptophan, tyrosine, 1- carnitine, 1-carnosine, glutamine alpha ketoglutarate and alpha-L-poly lactate.

[00476] Electrolytes used with the formulations herein include, but are not limited to, sodium chloride, sodium acetate, acidic sodium citrate, acidic sodium phosphate, sodium chloride, sodium bicarbonate, sodium bromide, sodium citrate, sodium lactate, sodium molybdate, sodium phosphate, anhydrous sodium sulphate, sodium sulphate, sodium tartrate, sodium benzoate, sodium selenite, and other sodium salts and mixtures thereof; potassium chloride, potassium acetate, potassium bicarbonate, potassium bromide, potassium citrate, potassium-D- gluconate, monobasic potassium phosphate, potassium tartrate, potassium sorbate, potassium iodide, and other potassium salts and mixtures thereof; magnesium carbonate, magnesium citrate, magnesium oxide, magnesium phosphate, as well as other magnesium salts and mixtures thereof; calcium chloride, calcium carbonate, calcium chelate, calcium di-phosphate, calcium lactate, calcium phosphate tribasic and other calcium salts and mixtures thereof. Such electrolytes may be included in the formulations described herein in proportions and amounts suitable to replenish salts lost during exercise or illness or otherwise depleted.

[00477] Anti-inflammatory agents for use within the formulations and methods herein include, but are not limited to, extracts from plants such as maqui berry, milk thistle, skull cap, red raspberry, red sour cherry, green tea and hops.

[00478] Other agents which may be used in the compositions and methods described herein include anti-nausea agents including, but not limited to, extracts from peppermint, ginger and chamomile.

[00479] A further agent which may be used in the compositions and methods described herein includes analgesic agents such as, but not limited to, white willow bark.

[00480] The formulations and methods described herein may additionally include herbal supplements and extracts with beneficial properties including, but not limited to, passion flower, horny goat weed, skullcap, milk thistle, Echinacea, dandelion leaf St. John's wort, green tea, black tea, chamomile or peppermint, or an extract thereof.

[00481] The formulations and methods described herein may further include plants with beneficial properties including, but not limited to, guarana seeds, acerola berries, coconut water, yerba mate, acai berry, ginseng root, panax ginseng root, ginkgo biloba, white willow bark, acacia, ashwagandha, chokeberry, elderberry, cranberry, maqui berry, blueberry, pomegranate, rooibos, goji berry, elder berry, valerian, seabuckthorn, yumberry, blackberry, astragalus, damiana, and ginger.

[00482] Energy boosters that may increase performance and are contemplated for use within the methods and formulations described herein include, but are not limited to, creatine ethyl ester, creatine monohydrate, magnesium creatine chelate, creatine hydrochloride, creatine nitrate, creatine monohydrate and royal jelly.

[00483] Useful flavonoids within the compositions and methods of the present invention are present in chamomile extract, cocoa powder, red grape, black tea, and white tea, ginkgo biloba, berries, parsley, and green tea some or all of which may be included in the compositions and methods described herein.

[00484] Useful sedatives for use within the compositions and methods described herein include, but are not limited to, lavender, lemon balm, lemongrass, linden, oatstraw, St. John's wart, valerian root, kava kava, hops and passion flower.

[00485] Stimulants for use within the methods and compositions described herein include, but are not limited to, caffeine, citicoline, d-glucuronolactone, guarana extract, ginseng, concentrated green tea, green coffee beans, glucuronolactone, guarana, panax ginseng, panax quinquefolius, Siberian ginseng, and theobromine.

[00486] Additional agents which may be included in the formulations and methods described herein are immune boosters including, but not limited to, Echinacea and astragalus root.

[00487] Flavoring agents for use with the compositions and methods described herein include, but are not limited to fruit juice, vegetable juice, milk solids, fruit flavors, herbal flavor and mixtures thereof. The fruit juice can be any citrus juice, non-citrus juice, or mixture thereof, which is known for use in dilute juice beverages. The juice can be derived from, but not limited to, apple, cranberry, pear, peach, plum, apricot, nectarine, grape, guava, cherry, currant, raspberry, gooseberry, elderberry, blackberry, blueberry, strawberry, lemon, lime, mandarin, orange, tomato, lettuce, dandelion, rhubarb, pineapple, coconut, pomegranate, kiwi, mango, papaya, banana, watermelon, passion fruit, tangerine, and cantaloupe. The vegetable juice can be any vegetable juice generally consumed including but not limited to, celery, spinach, cabbage, watercress, carrot, beet, spirulina, sweet potato, kale, romaine, collard greens, endive, escarole, bok Choy, fennel, parsley, wheat grass, or cucumber. Such fruit and vegetable juices may or may not have additional beneficial properties such as antioxidants and/or flavonoids.

[00488] Formulations and methods herein may additionally include a protein source. Protein sources include, but are not limited to, milk solids, calcium caseinate, whey protein concentrate, whey protein isolate, whey protein hydrolysate, soy protein, casein hydrolysate, rice protein, wheat protein, corn protein, partially hydrolyzed whey protein, or ultra-filtered whey protein.

[00489] Formulations and methods herein may further include one or more sweeteners or other carbohydrate source. Such sweeteners include, but are not limited to, acesulfame potassium, aspartame, cane sugar, corn syrup, crystalline fructose, dextrose, D-ribose, fructose, glucose, glucose-fructose syrup, high fructose com syrup, high fructose liquid sugar, honey, maltodextrin, sorbitol, stevia, sucralose. sucrose, sugar, trehalose, truvia or xylitol.

[00490] Further additional or adjunctive therapeutic agents may include but are not limited to, probenecid, allopurinol, nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, corticosteroids, uricosuric agents, xanthine oxidase inhibitors, losartan, fenofibrate, urate oxidase, Y-700, COX-2 inhibitors, analgesics, corticosteroids disease-modifying anti rheumatic drugs, antibiotics, vasodepressors, sulfasalazine, radiation therapy, chemotherapy, duloxetin, milnacipran, gabapentin, pregabalin, and benzaldehyde derivatives such as those described in U.S. patent application Ser. No. 12/418,342, incorporated herein by reference in its entirety.

[00491] The use of these additional or adjunctive agents in conjunction with the nitric oxide increasing agents of the present invention may increase the effectiveness of the therapeutic agents and/or decrease the amount of such agents that may be required to optimize health.

[00492] The amount, timing and mode of delivery of compositions of the invention comprising an effective amount of a base solution of the present invention will be routinely adjusted on an individual basis, depending on such factors as weight, age, gender, and condition of the individual, the severity of the symptoms, whether the administration is prophylactic or therapeutic, and on the basis of other factors known to effect drug delivery, absorption, pharmacokinetics, including, but not limited to, half-life, and efficacy.

[00493] Effective doses may be extrapolated from dose-response curves derived from in vitro or animal model test systems. Such animal models and systems are well known in the art. The precise dose to be employed will also depend on the route of administration, the seriousness of the disease or disorder, and body size, and should be decided according to the judgment of the practitioner and each patient's circumstances. [00494] The formulations may be presented in unit-dose or multi-dose containers. Preferred unit dosage formulations are those containing a daily dose or unit, daily sub-dose, as described herein above, or an appropriate fraction thereof, of the active ingredient(s). In one embodiment eight ounces of the prepared formulation is administered every four hours. In another embodiment, eight ounces of the prepared formulation is administered every three hours. In a further embodiment, 0.5 L is administered every eight hours. In still another embodiment, eight ounces of the prepared formulation is administered every two hours or fraction thereof. In exemplary embodiments, unit dose formulations are in 0.5 liters, or a multiple thereof.

[00495] Dosage forms of the compositions of the present invention include excipients recognized in the art of compounding as being suitable for the preparation of dosage units as discussed above. Such excipients include, without intended limitation, binders, fillers, lubricants, emulsifiers, suspending agents, sweeteners, flavorings, preservatives, buffers, and other conventional excipients and additives.

[00496] The compositions of the invention for altering physiological pH can thus include any one or combination of the following: a pharmaceutically acceptable carrier or excipient; other medicinal agent(s); pharmaceutical agent(s); adjuvants; buffers; preservatives; diluents; and various other pharmaceutical additives and agents known to those skilled in the art. These additional formulation additives and agents will often be biologically inactive and can be administered to patients without causing deleterious side effects or interactions with the active agent.

[00497] Additional compositions of the invention can be prepared and administered in any of a variety of inhalation or nasal delivery forms known in the art. Devices capable of depositing aerosolized formulations in the sinus cavity or pulmonary alveoli of a patient include metered dose inhalers, nebulizers, sprayers, and the like. Methods and compositions suitable for pulmonary delivery of drugs for systemic effect are well known in the art. Suitable formulations, wherein the carrier is a liquid, for administration, as for example, a nasal spray or as nasal drops, may include aqueous or oily solutions of calcium hydroxide and any additional active or inactive ingredient(s).

[00498] Yet additional formulations are provided for powders that further comprise that comprise a fortifying agent as a carrier. The carrier may be any solid or semisolid compound that is suitable for use in ingestible compositions and is compatible with the other ingredients in the composition. Preferred solid or semisolid carriers include water soluble or water suspendible macronutrients. Suitable carriers include, but are not limited to, carbohydrates and proteins. Exemplary carbohydrate carriers include simple sugars (e.g., glucose, fructose, or sucrose); complex sugars (e.g., maltodextrins, fructo-oligosaccharides, or inulin); starches (e.g., corn starch modified corn starch, potato starch, or rice starch); cellulosics (e.g., powdered cellulose, microcrystalline cellulose, or hemicellulose), sugar alcohols (e.g., xylitol, mannitol, sorbitol, or maltitol); and combinations thereof. Exemplary protein carriers include milk proteins (e.g., casein, caseinate, or whey); animal proteins (e.g., beef, poultry, or fish); vegetable proteins (e.g., bean, pea, or potato); cereal proteins (e.g., rice or wheat), and combinations thereof. A preferred example of a suitable carrier is nonfat dry milk powder, which comprises a combination of simple sugars (e.g., lactose) and proteins (e.g., casein and whey).

[00499] The carrier may also be in the form of an aqueous solution, emulsion, or suspension comprising a compound that is suitable for use in ingestible compositions and is compatible with the other ingredients in the composition. Preferred liquid carriers comprise water and water soluble or water suspendible macronutrients. Suitable liquid carriers include, but are not limited to, liquids comprising carbohydrates or proteins. Exemplary liquid carriers include fluid whole milk, fluid skim milk, fluid condensed milk, fluid evaporated milk, aqueous starch slurries, liquid sugar solutions, corn syrups, diluted corn syrups, honey, diluted honey, and combinations thereof. A preferred example of a suitable liquid carrier is fluid skim milk, which comprises a combination of simple sugars (e.g., lactose) and proteins (e.g., casein and whey).

[00500] The carrier may be in the fortifying powder at about 40 wt % to about 88 wt %, as a percentage of the weight of the fortifying powder. The carrier may be in the fortifying powder at about 42 wt % to about 85 wt %, including about 45 wt % to about 82 wt %, about 48 wt % to about 80 wt %, about 50 wt % to about 78 wt %, about 52 wt % to about 75 wt %, about 55 wt % to about 72 wt %, about 58 wt % to about 70 wt %, about 60 wt % to about 68 wt %, about 62 wt % to about 66 wt %, and about 63 wt % to about 65 wt %, as a percentage of the weight of the fortifying powder. The carrier may be in the fortifying powder at about 40 wt %, at about 43 wt %, at about 46 wt %, at about 49 wt %, at about 50 wt %, at about 53 wt %, at about 56 wt %, at about 59 wt %, at about 60 wt %, at about 64 wt %, at about 67 wt %, at about 70 wt %, at about 73 wt %, at about 75 wt %, at about 77 wt %, at about 80 wt %, at about 84 wt %, at about 86 wt %, and at about 88 wt %, as a percentage of the weight of the fortifying powder.

[00501] The carrier may be added to the fortifying powder at different stages during the preparation of the fortifying powder. In a preferred embodiment, the carrier is dissolved or suspended in an aqueous solution or suspension. This aqueous liquid comprising the carrier is mixed with the mixture of the MDG oil, lipophilic nutrient, and phospholipid. [00502] Lecithin may be in the fortifying agent at about 1 wt % to about 12 wt %, as a percentage of the weight of the fortifying powder. Lecithin may be in the fortifying powder at about 1.1 wt % to about 11 wt %, including about 1.2 wt % to about 10 wt %, about 1.4 wt % to about 9 wt %, about 1.5 wt % to about 8 wt %, about 1.7 wt % to about 7 wt %, about 1.8 wt % to about 6 wt %, about 1.9 wt % to about 5 wt %, about 2 wt % to about 4.5 wt %, about 2.2 wt % to about 4.3 wt %, about 2.4 wt % to about 4.1 wt %, about 2.6 wt % to about 4 wt %, about 2.8 wt % to about 3.8 wt %, and about 3.0 wt % to about 3.5 wt % , as a percentage of the weight of the fortifying powder. Lecithin may be in the fortifying powder at about 1 wt %, at about 1.1 wt %, at about 1.2 wt %, at about 1.3 wt %, at about 1.4 wt %, at about 1.5 wt %, at about 1.6 wt %, at about 1.7 wt %, at about 1.8 wt %, at about 1.9 wt %, at about 2.0 wt %, at about 2.3 wt %, at about 2.5 wt %, at about 2.7 wt %, at about 2.9 wt %, at about 3 wt %, at about 3.1 wt %, at about 3.3 wt %, at about 3.5 wt %, at about 3.7 wt %, at about 3.9 wt %, at about 4 wt %, at about 4.1 wt %, at about 4.3 wt %, at about 4.5 wt %, at about 4.7 wt %, at about 4.9 wt %, at about 5 wt %, at about 5.5 wt %, at about 6 wt %, at about 6.5 wt % at about 7 wt %, at about 7.5 wt %, at about 8 wt %, at about 8.5 wt %, at about 9 wt %, at about 9.5 wt %, at about 10 wt %, at about 11 wt %, and at about 12 wt %, as a percentage of the weight of the fortifying powder.

[00503] The products within the scope of this invention may take a variety of forms. For example, the product may be manufactured and sold as a ready-to-drink beverage for immediate consumption by a mammalian subject. The compositions described herein may be preferred in concentrate or powder form to be reconstituted for use by a mammalian subject by the addition of water. Such reconstitution is made with the requisite amounts of water to ensure that the beverage to be consumed contains the active components in the proportions previously noted. In some embodiments, liquid formulations as described herein may be sold as part of a kit. The kits of the present invention comprise one or more compositions of the present invention together with the, information which informs a user of the kit, by words, pictures, and/or the like, that use of the kit will provide one or more general health and/or general physiological benefits including, but not limited to, health and performance optimizing, illness preventing, energy level increasing, hydration increasing, recovery time decreasing, muscle protecting and stamina increasing benefits and which informs the user of the method of monitoring their low levels of nitric oxide levels.

[00504] The invention disclosed herein will also be understood to encompass methods and compositions comprising a base solution using in viva metabolic products of the said compounds (either generated in viva after administration of the subject precursor compound, or directly administered in the form of the metabolic product itself). Such products may result, for example, from the oxidation, reduction, hydrolysis, amidation, esterification and the like of the administered compound, primarily due to enzymatic processes. Accordingly, the invention includes methods and compositions of the invention employing compounds produced by a process comprising contacting a base solution of the present invention with a mammalian subject for a period of time sufficient to yield a metabolic product thereof.

[00505] The above disclosure generally describes the present invention. A more complete understanding can be obtained by referring to the following examples. These examples are described solely for purposes of illustration and are not intended to limit the scope of the invention. Although specific terms have been employed herein, such terms are intended for descriptive use and not for purposes of limitation.

[00506] In the detailed description of exemplary embodiments of the disclosure, specific exemplary embodiments in which the disclosure may be practiced are described in sufficient detail to enable those skilled in the art to practice the disclosed embodiments. For example, specific details such as specific method orders, structures, elements, and connections have been presented herein. However, it is to be understood that the specific details presented need not be utilized to practice embodiments of the present disclosure. It is also to be understood that other embodiments may be utilized and that logical, architectural, programmatic, mechanical, electrical and other changes may be made without departing from general scope of the disclosure. The following detailed description is, therefore, not to be taken in a limiting sense, and the scope of the present disclosure is defined by the appended claims and equivalents thereof.

[00507] References within the specification to “one embodiment,” “an embodiment,” “embodiments”, or“one or more embodiments” are intended to indicate that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present disclosure. The appearance of such phrases in various places within the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments mutually exclusive of other embodiments. Further, various features are described which may be exhibited by some embodiments and not by others. Similarly, various requirements are described which may be requirements for some embodiments but not other embodiments.

[00508] While the disclosure has been described with reference to exemplary embodiments, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the disclosure. In addition, many modifications may be made to adapt a particular system, device or component thereof to the teachings of the disclosure without departing from the essential scope thereof. Therefore, it is intended that the disclosure not be limited to the particular embodiments disclosed for carrying out this disclosure, but that the disclosure will include all embodiments falling within the scope of the appended claims. Moreover, the use of the terms first, second, etc. do not denote any order or importance, but rather the terms first, second, etc. are used to distinguish one element from another.

[00509] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the disclosure. As used herein, the singular forms“a”, “an” and“the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises” and/or “comprising,” when used in this specification, specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof.

[00510] The description of the present disclosure has been presented for purposes of illustration and description but is not intended to be exhaustive or limited to the disclosure in the form disclosed. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope of the disclosure. The described embodiments were chosen and described in order to best explain the principles of the disclosure and the practical application, and to enable others of ordinary skill in the art to understand the disclosure for various embodiments with various modifications as are suited to the particular use contemplated.