Dileucine Compositions and Methods of Using Same

Abstract

Disclosed herein are compositions and methods for promoting weight loss and / or preventing obesity; enhancing athletic performance / endurance; enhancing muscle function; enhancing cognitive function; promoting weight management; enhancing cardiovascular health; enhancing blood flow; reducing inflammation; and / or regulating immunity.In certain embodiments, the disclosed method comprises administering to subject the composition comprising the combination of dileucine and paraxanthine, and / or dileucine and L-arginine, and / or dileucine and leucine.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Patent Application No. 63 / 451,166, filed March 9, 2023, entitled "Dileucine Compositions and Methods of Using the Same," which is incorporated herein by reference in its entirety pursuant to 35 U.S.C. § 119(e). [Background technology]

[0002] Obesity is a serious problem in Western countries, with an estimated prevalence ranging from 30% to 50% of the middle-aged population. 2 and obesity (defined as a BMI of 30 kg / m or more). 2 The number of Americans who are overweight or obese (defined as those overweight or obese) has been increasing since 1960, and the trend shows no signs of slowing. Today, approximately 64.5% of adult Americans (approximately 199 million people) are overweight or obese. Obesity is becoming a growing concern as the number of obese people continues to increase and more is learned about its negative health effects. Obesity can lead to type 2 diabetes, heart disease, and some cancers. Each year in the United States, at least 300,000 people die from obesity, and the total medical costs of obese American adults total more than $147 billion. There is a need in the art for compositions and methods for more effectively achieving weight loss. Summary of the Invention [Means for solving the problem]

[0003]

[0003] Disclosed herein are compositions comprising paraxanthine and dileucine or L-arginine. According to certain embodiments, dileucine is present in an amount of about 10 mg to about 5,000 mg. In further embodiments, dileucine is present in an amount of about 25 mg to about 2,500 mg. In certain embodiments, paraxanthine is present in an amount of about 2 mg to about 800 mg. In further embodiments, paraxanthine is present in an amount of about 20 mg to about 600 mg. In yet further embodiments, paraxanthine is present in an amount of about 50 mg to about 400 mg. According to still further embodiments, L-arginine is present in an amount of about 500 mg to about 6,000 mg. In yet further embodiments, L-arginine is present in an amount of about 1,000 mg to about 3,000 mg. According to certain implementations, the L-arginine is in the form of free, salt, bonded arginine silicate complex, and / or arginine alpha-ketoglutarate.

[0004]

[0004] Also disclosed herein are methods for increasing muscle strength, muscle size, and / or muscle function, comprising administering to a subject a composition disclosed herein. In certain aspects of such embodiments, the composition further comprises one or more compounds selected from the list consisting of isoleucine, leucine and valine, histidine, lysine, methionine, phenylalanine, threonine, tryptophan, valine, creatine, cysteine, glutamine, glycine, proline, tyrosine, carnitine, β-alanine, taurine, β-hydroxy-β-methylbutyrate, omega-3 fatty acids, vitamin D, whey protein, and other protein extracts from animal, plant, or fermentation sources.

[0005]

[0005] Further disclosed herein is a method of increasing exercise capacity in a subject by administering to the subject a composition disclosed herein.

[0006] Further disclosed herein are methods of increasing exercise capacity and / or endurance in a subject by administering the compositions disclosed herein.

[0006]

[0007] Also disclosed herein is a method for promoting weight loss in a subject, comprising administering a composition disclosed herein. In certain implementations, the composition further comprises one or more compounds selected from the list consisting of caffeine, green tea, capsaicin, Garcinia cambogia, yohimbine, and bitter orange. In yet further implementations, weight loss is promoted through enhancing lipolysis in a subject, and the composition further comprises one or more compounds selected from the list consisting of caffeine, green tea extract, L-carnitine, Garcinia cambogia (hydroxycitric acid), capsaicin, ginseng, taurine, silk peptide, catechol, epigallocatechin gallate (EGCG), catechin, proanthocyanidin, and octacosanol.

[0007]

[0008] Further disclosed herein is a method for enhancing cognitive ability in a subject by administering the compositions disclosed herein.In certain aspects of such embodiments, the enhancement of cognitive function is measured by increasing one or more of attention, information acquisition, information processing, working memory, short-term memory, long-term memory, anterograde memory, retrograde memory, memory retrieval, discrimination learning, decision-making, inhibitory response control, attentional set shifting ability, delayed reward reinforcement learning, reversal learning, temporal integration of spontaneous behavior, processing speed, reasoning, problem solving and / or social cognition.

[0008]

[0009] Further disclosed herein are methods for treating an inflammatory disease or condition in a subject in need thereof by administering a composition disclosed herein. In certain implementations of such embodiments, the composition further comprises an additional anti-inflammatory agent, wherein the additional anti-inflammatory agent exerts an anti-inflammatory effect by inhibiting prostaglandins, increasing macrophage-mediated phagocytosis, suppressing cytokine-driven inflammation, inhibiting cytokines, inhibiting histone deacetylation, inhibiting kinases, stimulating PPARs, and / or inhibiting proteases.

[0009]

[0010] Further disclosed herein are methods of enhancing joint health in a subject in need thereof by administering the compositions disclosed herein.

[0011] Further disclosed herein is a method for enhancing immune function in a subject by administering the composition disclosed herein. In a specific implementation of such an embodiment, the composition may be selected from the group consisting of cyclosporine, tacrolimus, rapamycin, omega-3 fatty acids, curcumin, S-adenosylmethionine, zinc, green tea extract, frankincense (Boswellia serrata resin), capsaicin, cat's claw (Uncaria tomentosa and Uncaria guianensis), Schizonepeta tenuifolia, pomegranate, Moringa oleifera, Ecklonia cava, limonene, sulphonyl benzoate, sulforaphane, Angelica gigas, Ascophyllum nodosum, Scutellaria baicalensis, celery seed extract, sesamin, feverfew, taurine, rosmarinic acid, Evodia rutaecarpa, green tea catechins, punicalagins, Artemisia Iwayomogi, Pyrroloquinoline Quinone, N-Acetyl Cysteine, King Oyster Mushroom, Methylsulfonylmethane, Alpha-Lipoic Acid, Pine Pollen, Sophora flavescens, Ophiopogon japonicus, Stephania tetrandra, Crataegus pinnatifida, Grape Seed Extract, Bladderwrack, Paederia foetida, Benfotiamine, Rubus coreanus, Punicic Acid, Sea Buckthorn, Hibiscus rosasinensis, Phellodendron amurense, Resveratrol, Quercetin, Rooibos, Olive Leaf Extract, Pterostilbene, Eucommia ulmoides, Diindolylmethane, Anatabine, Serrapeptase, Pelargonidin, Watercress, Astaxanthin, Piceatannol, Fish Oil, Glutathione, Orthosiphon stamineus, Aronia melanocarpa, Blueberry, Tripterygium wilfordii, Boerhaavia diffusa, whey protein, bromelain, Panax ginseng, Aloe vera, cocoa extract, nettle, garlic, Centellaasiatica, Astragalus membranaceus, Dendrobium, Vitamin C, Spirulina, Berberine, Ganoderma lucidum, Vitamin C, Vitamin D, Vitamin E, Lutein, Leucine, Dileucine, Trileucine, Tetraleucine, Pau d'Arco, AHCC, Rhodiola, Ashwagandha, Shiitake, Maitake, Coriolus versicolor, Monolaurin, Lysine, Ergothioneine, Medium Chain Triglycerides (MCT), and Butyrate.

[0010]

[0012] Further disclosed herein are methods of enhancing cardiovascular health in a subject by administering the compositions disclosed herein.

[0013] Further disclosed herein are methods of enhancing blood flow in a subject by administering the compositions disclosed herein.

[0011]

[0014] While multiple embodiments are disclosed, still other embodiments of the present disclosure will become apparent to those skilled in the art from the following detailed description, which shows and describes exemplary embodiments of the presently disclosed apparatus, systems, and methods. It will be understood that the presently disclosed apparatus, systems, and methods are capable of modification in various obvious aspects, all without departing from the spirit and scope of the present disclosure. Accordingly, the drawings and detailed description are to be regarded as illustrative in nature and not as restrictive. DETAILED DESCRIPTION OF THE INVENTION

[0012]

[0015] Before the present compounds, compositions, articles, systems, devices, and / or methods are disclosed and described, it is to be understood that these are not limited to particular synthetic methods, unless otherwise specified, or to particular reagents, unless otherwise specified, which can, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, example methods and materials are now described.

[0013]

[0016] Ranges may be expressed herein as from "about" one particular value and / or to "about" another particular value. When such a range is expressed, a further aspect includes from the one particular value and / or to the other particular value. Similarly, when values ​​are expressed as approximations, by use of the antecedent "about," it is understood that the particular value stated forms a further aspect. It is further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint. It is also understood that there are a number of values ​​disclosed herein, and that each value is herein disclosed "about" that particular value as well as the particular value itself. For example, if the value "10" is disclosed, then "about 10" is also disclosed. It is also understood that each intervening unit value is disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed.

[0014]

[0017] As used herein, the term "subject" refers to the target of administration, e.g., a human subject. Thus, the subject of the methods disclosed herein can be a vertebrate, such as a mammal, fish, bird, reptile, or amphibian. Alternatively, the subject of the methods disclosed herein can be a human, non-human primate, horse, pig, rabbit, dog, sheep, goat, cow, cat, guinea pig, or rodent. The term does not denote a particular age or sex. Thus, adult and newborn / baby subjects and fetuses / babies are intended to be encompassed, regardless of gender. In one embodiment, the subject is a mammal. A patient refers to a subject suffering from a disease or disorder. The term "patient" encompasses human and veterinary subjects. In some embodiments of the methods disclosed herein, the subject has been diagnosed with one or more weight disorders, inflammatory disorders, cardiovascular disorders, and / or cognitive dysfunction in need of treatment prior to the administering step. In some aspects of the methods disclosed herein, the subject has been diagnosed with a need for increased weight loss prior to the administering step.

[0015]

[0018] The term "overweight" refers to an individual with a BMI of 25 kg / m 2 More than 30kg / m 2 The terms "overweight" and "pre-obese" are used interchangeably.

[0019] As used herein, the term "obesity" refers to an individual with a BMI of 30 kg / m 2 According to the WHO definition, the term obesity can be classified as follows: the term "Class I obesity" is defined as a BMI of 30 kg / m or more; 2 More than 35kg / m 2 The term "Class II obesity" refers to a BMI of less than 35 kg / m 2 More than 40kg / m 2 The term "Class III obesity" refers to a BMI of less than 40 kg / m 2 This is the above state.

[0016]

[0020] As used herein, the terms "manage," "managing," and "management" include preventing, delaying, or reducing the severity of a disease, disorder, or condition in a patient already suffering from a fat-related body composition or weight disorder, such as obesity, lipodystrophy, diabetes, or metabolic syndrome, fibrosis, and cancer. The terms "manage," "managing," and "management" include modulating the threshold, onset, and / or duration of a fat-related body composition or weight disorder, such as obesity, lipodystrophy, diabetes, or metabolic syndrome, fibrosis, and cancer, or changing how a patient deals with a fat-related body composition or weight disorder.

[0017]

[0021] As used herein, the term "treatment" refers to the medical management of a patient with the goal of curing, ameliorating, stabilizing, or preventing a disease, pathological condition, or disorder. This term encompasses active treatment, i.e., treatment specifically aimed at reversing a disease, pathological condition, or disorder, and also encompasses causal treatment, i.e., treatment aimed at eliminating the cause of the associated disease, pathological condition, or disorder. In addition, this term encompasses palliative treatment, i.e., treatment designed to alleviate symptoms rather than cure the disease, pathological condition, or disorder; preventative treatment, i.e., treatment aimed at minimizing or partially or completely inhibiting the onset of the associated disease, pathological condition, or disorder; and supportive treatment, i.e., treatment used to supplement another specific therapy aimed at reversing the associated disease, pathological condition, or disorder. In various embodiments, the term encompasses all treatments of subjects, including mammals (e.g., humans), and includes (i) preventing the onset of the disease in subjects who may be predisposed to the disease but have not yet been diagnosed as having the disease, (ii) inhibiting the disease, i.e., preventing its development, or (iii) alleviating the disease, i.e., causing regression of the disease. In one embodiment, the subject is a mammal, e.g., a primate, and in a further embodiment, the subject is a human. The term "subject" also encompasses domestic animals (e.g., cats, dogs, etc.), livestock (e.g., cattle, horses, pigs, sheep, goats, etc.), and laboratory animals (e.g., mice, rabbits, rats, guinea pigs, fruit flies, etc.).

[0018]

[0022] As used herein, the term "prevent" or "preventing" refers to preventing, preventing, forestalling, stopping or impeding something from happening, especially by prior action. It is understood that where the words reduce, inhibit or prevent are used herein, unless otherwise indicated, the use of the other two words is also expressly disclosed.

[0019]

[0023] As used herein, the term "diagnosed" means having undergone a physical examination by a skilled person, such as a physician, and found to have a condition that can be diagnosed or treated with a compound, composition, or method disclosed herein. For example, "diagnosed with obesity" means having undergone a physical examination by a skilled person, such as a physician, and found to have a condition that can be diagnosed or treated with a compound or composition that can reduce body mass (body weight). As a further example, "diagnosed as needing weight loss" refers to having undergone a physical examination by a skilled person, such as a physician, and found to have a condition characterized by excess body fat or other disorder in which reducing body fat would be beneficial to the subject. Such a diagnosis may be related to a disorder discussed herein, such as obesity, metabolic syndrome, etc.

[0020]

[0024] As used herein, phrases such as "identified as needing treatment for a disorder" refer to the subject being selected based on the need for treatment for the disorder.For example, a subject can be identified as needing treatment for a disorder (for example, a disorder associated with excess adipose tissue) based on a previous diagnosis by a skilled person, and then undergo treatment for the disorder.It is contemplated that in one embodiment, the identification can be performed by a person different from the person who makes the diagnosis.It is also contemplated that in a further embodiment, the administration can be performed by the person who subsequently performed the administration.

[0021]

[0025] As used herein, the terms "administering" and "administration" refer to any method of providing a composition to a subject. Such methods are well known to those skilled in the art and include, but are not limited to, oral administration, transdermal administration, administration by inhalation, nasal administration, topical administration, intravaginal administration, ocular administration, intraaural administration, intracerebral administration, rectal administration, sublingual administration, buccal administration, and parenteral administration, including injection administration, such as intravenous administration, intraarterial administration, intramuscular administration, and subcutaneous administration. Administration can be continuous or intermittent. In various embodiments, the preparation can be administered therapeutically, i.e., to treat an existing disease or condition. In further various embodiments, the preparation can be administered prophylactically, i.e., to prevent a disease or condition.

[0022]

[0026] As used herein, the term "cardiovascular disease" or "cardiovascular disorder" is used broadly herein to include all diseases and pathological conditions whose etiology is associated with vascular abnormalities, such as atherosclerotic plaque formation (including stable or unstable / vulnerable plaques), atherosclerosis, arteriosclerosis, arteriolosclerosis, and high systemic exposure to lipopolysaccharide (LPS). The term "cardiovascular disease" or "cardiovascular disorder" also encompasses diseases and pathological conditions in which inhibition of atherosclerotic plaque formation is beneficial. Cardiovascular diseases include, but are not limited to, coronary atherosclerosis, coronary microvascular disease, stroke, carotid artery disease, peripheral artery disease, ischemia, coronary artery disease (CAD), acute coronary syndrome (ACS), coronary heart disease (CHD), conditions related to CAD and CHD, cerebrovascular disease, peripheral vascular disease, aneurysm, vasculitis, venous thrombosis, diabetes, as well as metabolic syndrome, chronic kidney disease, remote tissue injury after ischemia-reperfusion, and cardiopulmonary bypass. Specifically, all cardiovascular diseases whose onset, development, or progression can be controlled by inhibiting atherosclerotic plaque formation are included in this group.

[0023]

[0027] As used herein, "enhancing cardiovascular health" includes preventing, treating, and maintaining protection against hypercholesterolemia and hypertension, as well as achieving and maintaining normal ratios of LDL, HDL, and triglycerides.

[0024]

[0028] As used herein, "inflammatory diseases or conditions" for which the compositions and methods disclosed herein may be used include, but are not limited to, acquired immune deficiency syndrome (AIDS), acute disseminated encephalomyelitis (ADEM), Addison's disease, agammaglobulinemia, allergic diseases, alopecia areata, Alzheimer's disease, amyotrophic lateral sclerosis, ankylosing spondylitis, antiphospholipid syndrome, antisynthetase syndrome, arterial plaque disorder, and the like. disorder), asthma, atherosclerosis, atopic allergy, atopic dermatitis, autoimmune aplastic anemia, autoimmune cardiomyopathy, autoimmune enteropathy, autoimmune hemolytic anemia, autoimmune hepatitis, autoimmune hypothyroidism, autoimmune inner ear disease, autoimmune lymphoproliferative syndrome, autoimmune peripheral neuropathy, autoimmune pancreatitis, autoimmune polyendocrine syndrome, autoimmune progesterone dermatitis, autoimmune thrombocytopenic purpura, autoimmune urticaria, autoimmune uveitis, Baro's disease / Baro's concentric sclerosis, Behçet's disease, Berger's disease, Bickerstaff's encephalitis, Blau syndrome, bullous pemphigoid, Castleman's disease, celiac disease, Chagas' disease, chronic inflammatory demyelinating polyneuropathy, chronic recurrent multifocal osteomyelitis, chronic obstructive pulmonary disease, chronic venous stasis ulcer), Churg-Strauss syndrome, cicatricial pemphigoid, Cogan's syndrome, cold agglutinin disease, complement C2 deficiency, contact dermatitis, cranial arteritis, CREST syndrome, Crohn's disease, Cushing's syndrome, cutaneous leukocytoclastic vasculitis, Degos disease, Dercum's disease, dermatitis herpetiformis, dermatomyositis, type I diabetes, type II diabetes, diffuse cutaneous systemic sclerosis, Dressler's syndrome, drug-induced lupus , discoid lupus erythematosus, eczema, emphysema, endometriosis, enthesitis-related arthritis, eosinophilic fasciitis, eosinophilic gastroenteritis, eosinophilic pneumonia, epidermolysis bullosa acquisita, erythema nodosum, erythroblastosis fetalis, essential mixed cryoglobulinemia, Evans syndrome, fibrodysplasia ossificans progressiva, fibrosing alveolitis (or idiopathic pulmonary fibrosis), gastritis, gastrointestinal pemphigoid, Gaucher disease, glomerulonephritis, Goodpasture syndrome, Graves' disease, Guillain-Barré syndrome (GBS), Hashimoto's encephalopathy, Hashimoto's thyroiditis, heart disease,Henoch-Schönlein purpura, herpes gestationis (also known as pemphigoid of gestation), hidradenitis suppurativa, HIV infection, Hughes-Stovin syndrome, hypogammaglobulinemia, infectious diseases (e.g., bacterial infectious diseases), idiopathic inflammatory demyelinating diseases, idiopathic pulmonary fibrosis, idiopathic thrombocytopenic purpura, IgA nephropathy, inclusion body myositis, inflammatory arthritis, inflammatory bowel disease, inflammatory dementia, interstitial cystitis, interstitial pneumonia, juvenile idiopathic arthritis (also known as juvenile rheumatoid arthritis), Kawasaki disease, Lambert-Eaton myasthenic syndrome, leukocytoclastic vasculitis, lichen planus, lichen sclerosus , linear immunoglobulin A disease (LAD), lupoid hepatitis (also known as autoimmune hepatitis), lupus erythematosus, lymphomatoid granulomatosis, Majeed syndrome, cancer and other malignancies (e.g., sarcoma, Kaposi's sarcoma, lymphoma, leukemia, carcinoma, and melanoma), Meniere's disease, microscopic polyangiitis, Miller-Fisher syndrome, mixed connective tissue disease, molluscum contagiosum, Mukka-Habermann disease (also known as acute pityriasis lichenoides), multiple sclerosis, myasthenia gravis, myositis, narcolepsy, neuromyelitis optica (also known as Devic's disease), neuropathies, and neurological disorders. Myotonia, Ocular cicatricial pemphigoid, Opsoclonus-myoclonus syndrome, Ord's thyroiditis, Relapsing rheumatoid arthritis, PANDAS (Pediatric autoimmune neuropsychiatric disorders associated with streptococci), Paraneoplastic cerebellar degeneration, Parkinson's disorders, Paroxysmal nocturnal hemoglobinuria (PNH), Parry-Romberg syndrome, Parsonage-Turner syndrome, Parsplanitis, Pemphigus vulgaris, Peripheral arterial disease, Perivenous encephalomyelitis, POEMS syndrome, Polyarteritis nodosa, Polymyalgia rheumatica, Polymyositis, Primary biliary cirrhosis, Primary sclerosing cholangitis, Progressive inflammatory neuropathies rheumatoid arthritis, psoriasis, psoriatic arthritis, pyoderma gangrenosum, pure red cell aplasia, Rasmussen's encephalitis, Raynaud's phenomenon, relapsing polychondritis, Reiter's syndrome, restenosis, restless legs syndrome, retroperitoneal fibrosis, rheumatoid arthritis, rheumatic fever, sarcoidosis, schizophrenia, Schmidt's syndrome, Schnitzler's syndrome, scleritis, scleroderma, sepsis, serum sickness, Sjogren's syndrome, spondyloarthropathy, Still's disease (adult onset), stiff person syndrome, stroke, subacute bacterial endocarditis (SBE), Susac's syndrome, Sweet's syndrome, Sydenham's chorea, sympathetic ophthalmia, systemic lupus erythematosus, Takayasu's arteritisThese include temporal arteritis (also known as "giant cell arteritis"), thrombocytopenia, Tolosa-Hunt syndrome, transplant (e.g., heart / lung transplant) rejection, transverse myelitis, tuberculosis, ulcerative colitis, undifferentiated connective tissue disease, undifferentiated spondyloarthropathy, urticarial vasculitis, vasculitis, leukoplakia, and Wegener's granulomatosis.

[0025]

[0029] The terms "modulate," "modulating," "modulation," "enhance," "enhancing," and "enhancement" are used interchangeably herein to describe an enhanced ability to mount an immune response in any human or animal (such as, but not limited to, a dog, cat, rodent, horse, sheep, cow, pig, goat, donkey, chicken, or rabbit).

[0026]

[0030] As used herein, the term "substantially" refers to the complete or nearly complete extent or degree of an action, property, characteristic, state, structure, item, or result. For example, referring to an object being "substantially" enclosed would mean that the object is completely enclosed or nearly completely enclosed. The precise tolerance for deviation from absolute completeness may depend on the specific context. Generally, however, near completeness would mean close enough to achieve the same overall result as would be achieved if absolute and total completeness were achieved. The use of "substantially" is equally applicable when used in a negative sense to refer to the complete or nearly complete absence of an action, property, characteristic, state, structure, item, or result. For example, a composition that is "substantially" free of particles would be completely or nearly completely devoid of particles, and therefore the effect would be similar to that if the composition were completely devoid of particles. In other words, a composition that is "substantially" free of a component or element may actually contain that component or element, as long as no measurable effect of that component or element is observed.

[0027]

[0031] As used herein, the term "synergistic effect" or its grammatical variants refers to and includes the synergistic effect observed in the combination of two or more active compounds.In this synergistic effect, the activity of the combination of two or more active compounds exceeds the sum of the activities of each active compound alone.As used herein, the term "synergistically effective amount" refers to and includes the amount of two or more active compounds that produces the synergistic effect defined above.

[0028]

[0032] Disclosed herein are compositions and methods for promoting weight loss and / or preventing obesity; enhancing athletic performance / endurance; enhancing muscle function; enhancing cognitive function; promoting weight management; enhancing cardiovascular health; enhancing blood flow; reducing inflammation; and / or regulating immunity.In certain embodiments, the disclosed method comprises administering to subject the composition comprising the combination of dileucine and paraxanthine, and / or the combination of dileucine and L-arginine, and / or the combination of dileucine and leucine.

[0029]

[0033] Dileucine refers to a dipeptide composed of two L-leucines. In certain embodiments, dileucine can have the following structure:

[0030] [ka]

[0031] Dileucine is sometimes called L-leucyl-L-leucine or Leu-Leu and has the CAS number 3303-31-9.

[0034] In certain embodiments, compositions comprising dileucine, leucine, and a pharmaceutically acceptable carrier thereof are disclosed. In various embodiments, dileucine is present at about 10% to 90% (w / w). In further embodiments, dileucine is present at about 20% to 80% (w / w). In further embodiments, dileucine is present at about 30% to 70% (w / w). In further embodiments, dileucine is present at about 40% to 60% (w / w). In still further embodiments, dileucine is present at about 50% (w / w).

[0032]

[0035] In alternative embodiments, dileucine is present at about 10% to 90% (w / w) and leucine is present at about 90% to 10% (w / w). In further embodiments, dileucine is present at about 20% to 80% (w / w) and leucine is present at about 80% to 20% (w / w). In further embodiments, dileucine is present at about 30% to 70% (w / w) and leucine is present at about 70% to 30% (w / w). In further embodiments, dileucine is present at about 40% to 60% (w / w) and leucine is present at about 60% to 40% (w / w). In further embodiments, dileucine is present at about 50% (w / w) and leucine is present at about 50% (w / w).

[0033]

[0036] In certain aspects, the compositions of the present disclosure include a dileucine salt. In an exemplary embodiment, the composition is a dileucine acetate salt, which may have the following structure:

[0034] [ka]

[0035]

[0037] In certain embodiments, the compositions of the present disclosure include trileucine. Trileucine refers to a tripeptide composed of three L-leucines. In certain embodiments, trileucine has the following structure:

[0036] [ka]

[0037]

[0038] Trileucine is also called trileucine, LEU-LEU-LEU, H-LEU-LEU-LEU-OH, L-leucyl-leucine, leucyl-leucine, Leu-leu-leu crystalline, L-leucy-L-leucine, L-leucyl-L-leucine, L-leucyl-L-leucine, Leu-Leu-Leu-OH≧S)-2-((S)-2-((S)-2-amino-4-methylpentanamido)-4-methylpentanamido)-4-methylpentanoic acid.

[0038]

[0039] In a further aspect, the method of the present disclosure comprises administering to a subject a composition comprising a tripeptide comprising two L-leucine units and one amino acid or amino acid derivative. According to certain embodiments, the amino acid is selected from the group of branched-chain amino acids (BCAAs), including but not limited to isoleucine, leucine, and valine. In further embodiments, the amino acid is selected from the group of essential amino acids, including but not limited to histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. In yet further embodiments, the amino acid is selected from the group of conditionally essential amino acids, including but not limited to arginine, cysteine, glutamine, glycine, proline, and tyrosine. According to certain embodiments, the conditionally essential amino acid is tyrosine. In an exemplary embodiment, the composition comprises di-leucine tyrosine, having the following structure:

[0039] [ka]

[0040] In yet further embodiments, the amino acid is selected from the group of non-essential amino acids, including, but not limited to, alanine, aspartic acid, asparagine, glutamic acid, serine, selenocysteine, and pyrrolsine. In yet further embodiments, the amino acid derivative is selected from the group of creatine, carnitine, creatinol, β-alanine, taurine, and β-hydroxy-β-methylbutyrate.

[0041] In certain embodiments, methods are disclosed for reducing body weight and / or body fat in a subject, comprising administering to the subject an effective amount of a composition comprising at least one amino acid or peptide selected from dileucine, trileucine, and Leu-Leu-R (wherein R is an amino acid or amino acid derivative) and pharmaceutically acceptable salts thereof. In various embodiments, the at least one amino acid or peptide comprises leucine and dileucine and / or pharmaceutically acceptable salts thereof.

[0042] In certain embodiments, dileucine is present at about 10% (w / w) to about 90% (w / w). In further embodiments, dileucine is present at about 30% to 70% (w / w). In a further embodiment, dileucine is present at about 50% (w / w).

[0043] In various alternative embodiments, dileucine is present at about 10% to 90% (w / w) and leucine is present at about 90% to 10% (w / w) (based on the combined weight of leucine and dileucine). In further embodiments, dileucine is present at about 30% to 70% (w / w) and leucine is present at about 70% to 30% (w / w). In further embodiments, dileucine is present at about 50% (w / w) and leucine is present at about 50% (w / w). In all of the foregoing, % (w / w) refers to the percentage based on the combined weight of leucine and dileucine.

[0044] In these and other embodiments, administration of the composition to a subject synergistically increases the plasma level of leucine compared to administration of a composition that includes leucine but does not include dileucine. Additionally, administration of the composition to a subject synergistically reduces body weight and / or body fat compared to administration of a composition that includes leucine but does not include dileucine.

[0045] In various embodiments, the composition comprises at least about 95% dileucine and between about 0.1% and 5% trileucine, or pharmaceutically acceptable salts thereof. In further embodiments, the trileucine is present in an amount between about 0.1% and 3%, and the composition further comprises about 0.1% to 2% tetraleucine. In still further embodiments, the trileucine is present in an amount of about 0.4% and the tetraleucine is present in an amount of about 0.2%.

[0046] According to certain alternative embodiments, the composition comprises at least about 95% dileucine and between about 0.1% and 5% tetraleucine, and pharmaceutically acceptable salts thereof.

[0047] In certain aspects of the foregoing embodiments, the composition is substantially free of leucine.

[0048] In certain aspects, the dileucine of the compositions of the present disclosure is produced via bacterial fermentation. According to such embodiments, a fermentation method is used that utilizes di- / tri- / tetrapeptide-forming enzymes that directly link amino acids, followed by an extraction process.

[0048]

[0049] Paraxanthine or 1,7-dimethylxanthine is the dimethyl derivative of xanthine. Paraxanthine has the following structure:

[0049] [ka]

[0050]

[0050] The paraxanthine used in the compositions of the present disclosure may be derived from natural sources and / or synthetically and / or via fermentation.

[0051] In certain embodiments, the composition is formulated to provide a single dose of paraxanthine in the range of about 1 to about 1000 mg (e.g., about 1 mg, about 5 mg, about 10 mg, about 15 mg, about 20 mg, about 25 mg, about 30 mg, about 35 mg, about 40 mg, about 45 mg, about 50 mg, about 75 mg, 100, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, or about 1000 mg, etc., or any range or value therein).

[0051]

[0052] According to certain embodiments, the compositions of the present disclosure comprise paraxanthine and dileucine. In certain embodiments, paraxanthine is present in an amount of about 2 mg to about 800 mg. In further embodiments, paraxanthine is present in an amount of about 20 mg to about 600 mg. In still further embodiments, paraxanthine is present in an amount of about 50 mg to about 400 mg. In certain implementations, dileucine is present in an amount of about 10 mg to about 5,000 mg. In further embodiments, dileucine is present in an amount of about 25 mg to about 2,500 mg.

[0052]

[0053] In certain embodiments, the compositions of the present disclosure comprise dileucine and L-arginine. Arginine is an amino acid with the formula (HN)(HN)CN(H)(CH)CH(NH)COH. At physiological pH, the carboxylic acid is deprotonated (-CO-), and both the amino and guanidino groups are protonated to form cations. Only the L-arginine (symbol Arg or R) enantiomer is found in nature. Arginine is classified as a semi-essential or conditionally essential amino acid, depending on the individual's developmental stage and health status. The arginine used in the compositions of the present disclosure can be in the free form, a salt, a bound arginine silicate complex and / or arginine α-ketoglutarate, as well as other arginine sources known in the art.

[0053]

[0054] In certain embodiments, dileucine is present in an amount of about 10 mg to about 5,000 mg. In further embodiments, dileucine is present in an amount of about 25 mg to about 2,500 mg. In certain implementations of the above embodiments, L-arginine is present in an amount of about 500 mg to about 6,000 mg. In further embodiments, L-arginine is present in an amount of about 1,000 mg to about 3,000 mg. In certain embodiments, the composition comprises dileucine, paraxanthine, and L-arginine. nutritional supplement

[0055] The compositions of the present disclosure can be in the form of a dietary supplement or can themselves be used in combination with a dietary supplement, also referred to herein as a food supplement.

[0054]

[0056] Dietary supplements can be in many forms, such as tablets, capsules, softgels, gel capsules, liquids, or powders. Some dietary supplements can help ensure adequate dietary intake of essential nutrients, while others can help reduce the risk of disease. food products

[0057] The compositions of the present disclosure can be in the form of food products. Here, the term "food" is used broadly to encompass human food and beverages, as well as animal food and beverages (i.e., feed). Preferably, the food products are suitable for and designed for human consumption.

[0055]

[0058] The food product may be in the form of a liquid, solid or suspension, depending on the use and / or mode of application and / or mode of administration.

[0059] When in the form of a food product, the composition may comprise or be used in combination with one or more of a nutritionally acceptable carrier, a nutritionally acceptable diluent, a nutritionally acceptable excipient, a nutritionally acceptable adjuvant, or a nutritionally active ingredient.

[0056]

[0060] By way of example, the compositions of the present disclosure may be in the form of one of the following: fruit juice, whey protein-containing beverage: health or herbal tea, cocoa drink, coffee drink, yogurt and / or drinking yogurt, cheese, ice cream, dessert, confectionery, biscuit, cake, cake mix or cake filling, snack food, fruit filling, cake or donut icing, instant bread filling cream, cookie filling, ready-to-use bread filling, low-calorie filling, adult nutritional beverage, acidified soy / juice drink, nutritional or health bar, beverage powder, calcium-fortified soy milk, or calcium-fortified coffee drink. food ingredients

[0061] The compositions of the present disclosure may be in the form of a food and / or feed ingredient.

[0057]

[0062] As used herein, the term "food ingredient" or "feed ingredient" encompasses compositions that are or can be added to functional foods or foods as nutritional and / or dietary supplements for humans and animals.

[0058]

[0063] The food ingredient may be in liquid, suspension or solid form depending on the use and / or mode of application and / or mode of administration. functional food

[0064] The compositions of the present disclosure may be in the form of a functional food.

[0059]

[0065] As used herein, the term "functional food" means a food product that is not only capable of providing a nutritional benefit, but also capable of delivering additional beneficial effects to the consumer.

[0060]

[0066] Thus, functional foods are ordinary foods that incorporate components or ingredients (such as those described herein) that impart to the food a specific function other than a purely nutritional effect, such as a medical or physiological benefit.

[0061]

[0067] Although there is no legal definition of functional foods, most stakeholders in this field agree that functional foods are foods that are marketed as having specific health benefits beyond basic nutritional benefits.

[0062]

[0068] Among functional foods are nutraceuticals. Here, the term "nutraceutical" refers not only to foods that can provide nutritional benefits and / or taste satisfaction, but also to foods that can deliver therapeutic (or other beneficial) effects to the consumer. Nutraceuticals cross the traditional line between food and medicine. medical foods

[0069] The compositions of the present disclosure may be in the form of a medical food.

[0063]

[0070] "Medical food" means a food designed to be consumed or administered with or without medical supervision and intended for a specific dietary management or condition for which distinctive nutritional requirements based on generally accepted scientific principles have been established by medical evaluation. Methods of Use and / or Treatment

[0071] In certain embodiments, dileucine may be combined with one or more other chemical compounds (e.g., other active ingredients) to produce multiple positive effects in a subject. By varying the dosage of dileucine and / or the chemical compounds combined with dileucine, various targeted physiological effects can be selected. The composition may primarily provide a single benefit, or may simultaneously provide multiple benefits. athletic ability

[0072] Further disclosed herein is a method for enhancing performance or energy in a subject, comprising administering a composition disclosed herein to the subject. As used herein, the term "enhancing performance" refers to any enhancement of performance. Performance can be assessed in any manner. Some enhancements are easily measured. For example, in a timed event, performance enhancement can be assessed by improving time. Some performance-enhancing properties can be subjectively determined by the athlete, performer, or observer. In such cases, performance enhancement refers to subjective perception of performance as being enhanced, increased, faster, better, etc. In certain embodiments, the disclosed method is used to enhance athletic performance. "Athletic performance" refers to any professional or recreational activity in which a performer, e.g., an athlete, performs a physical activity, such as running, swimming, golf, bowling, archery, football, baseball, basketball, soccer, hiking, cycling, dancing, etc. In certain embodiments, athletic performance is enhanced through the enhancement of endurance in a subject. In other words, administering the composition of the present disclosure enhances the endurance level of a subject, thereby enhancing the athletic performance of the subject. In further embodiments, administering the composition to a subject increases cognitive ability, thereby enhancing athletic performance.

[0064]

[0073] In certain embodiments, upon administration of the composition, the subject experiences an increase in at least one of mood, energy, focus, concentration, or sexual desire, or a reduction in at least one of anxiety, fatigue, perception of effort, or perception of pain.

[0065]

[0074] In a further embodiment, the composition, when administered continuously to a subject, does not produce dependence in the subject and / or withdrawal symptoms in the subject when continued use is discontinued.

[0066]

[0075] Further disclosed herein is a method for increasing exercise endurance in a subject, the method comprising administering to the subject a composition disclosed herein. In certain implementations, the composition administered to the subject comprises dileucine and paraxanthine. In exemplary implementations, the administration of paraxanthine and dileucine results in a synergistic increase in exercise endurance in the subject compared to the administration of paraxanthine or dileucine alone.

[0067]

[0076] According to further embodiments, administering a composition of the present disclosure to a subject increases the subject's perceived level of energy. In exemplary implementations, the subject experiences at least about a 5 percent increase in energy. According to certain embodiments, the administered composition comprises L-theanine, phosphatidylcholine, α-GPC (L-α-glycerylphosphorylcholine), citicoline (cytidine diphosphate choline (CPD choline)), choline bitartrate, Bacopa Monnieri, phosphatidylserine, pilocarpine, and cevimeline, Ambura cearensis, Lippia sidoides, Paullinia cupana, Plathymiscium floribundum, tetrahydrocurcumin, and Solanum spp. asperum, and / or combinations thereof, caffeine, theobromine, naringin, hesperidin, 2-(dimethylamino)ethanol (DMAE), DMAE bitartrate, huperzine A, theacrine, methylliberin, B12, sulbutiamine, magnolia bark, ketones, MCT, omega-3, lutein, zeaxanthin, tyrosine and n-acetyl tyrosine, taurine, acetyl-l-carnitine, and / or combinations thereof (in addition to dileucine and / or paraxanthine).

[0068]

[0077] In certain aspects of the foregoing embodiments, wherein the composition comprises effective amounts of dileucine and paraxanthine, administration of paraxanthine and dileucine results in a synergistic enhancement of exercise performance in the subject compared to administration of paraxanthine or dileucine alone.

[0069]

[0078] In certain further aspects of the foregoing embodiments, wherein the composition comprises effective amounts of dileucine and L-arginine, administration of L-arginine and dileucine results in a synergistic increase in exercise performance in the subject compared to administration of L-arginine or dileucine alone. Muscle function

[0079] Further disclosed herein is a method for increasing muscle function in a subject, comprising administering to the subject a composition disclosed herein. In certain embodiments, disclosed herein is a method for promoting muscle growth through the administration of an effective amount of one or more compositions disclosed herein. In certain further embodiments, administering an effective amount of a composition disclosed herein results in an increase in muscle protein synthesis (MPS) levels in the subject. In yet further embodiments, administering an effective amount of a composition disclosed herein results in enhanced muscle accretion in the subject.

[0070]

[0080] In certain embodiments, disclosed herein is a method for promoting muscle growth through the administration of an effective amount of one or more compositions disclosed herein.In certain further embodiments, the administration of an effective amount of the composition disclosed herein results in an increase in muscle protein synthesis (MPS) levels in a subject.In yet further embodiments, the administration of an effective amount of the composition disclosed herein results in an enhancement of muscle growth in a subject.

[0071]

[0081] According to certain embodiments, the compositions disclosed herein can be administered in conjunction with a strength training regimen. As will be appreciated by those skilled in the art, administration of an effective amount of the disclosed compositions results in increased muscle strength and increased exercise capacity / ergogenesis in a subject.

[0072]

[0082] In one embodiment, compounds of the present disclosure inhibit muscle atrophy. In a further embodiment, compounds of the present disclosure increase muscle mass. In a still further embodiment, compounds of the present disclosure induce muscle hypertrophy. In a still further embodiment, compounds of the present disclosure inhibit muscle atrophy and increase muscle mass. In a still further embodiment, compounds of the present disclosure inhibit muscle atrophy and induce muscle hypertrophy. In a still further embodiment, the inhibition of muscle atrophy is in a subject. In a still further embodiment, the increase in muscle mass is in a subject. In a still further embodiment, the subject is a mammal. In a still further embodiment, the mammal is a human.

[0073]

[0083] In certain embodiments, administration of the compositions of the present disclosure is effective in preventing or treating age-related muscle atrophy or sarcopenia.In further embodiments, administration of the compositions of the present disclosure is effective in preventing or treating muscle atrophy associated with muscle stiffness, such as muscle atrophy often caused when a broken bone is immobilized in a cast.In still further embodiments, administration of the compositions of the present disclosure is effective in preventing or treating muscle atrophy associated with diseases such as cancer, also known as cachexia.

[0074]

[0084] According to certain embodiments, the composition is administered to a subject with sarcopenia. In various embodiments, the composition is administered in a therapeutically effective amount. In further embodiments, the composition is administered in a prophylactically effective amount (e.g., to a subject at risk of developing sarcopenia, cachexia, or immobilization-induced atrophy).

[0075]

[0085] In certain aspects, the composition further comprises one or more additional active ingredients for further enhancing muscle strength, size, and / or muscle function. In certain embodiments, the one or more additional active ingredients are amino acids. According to certain embodiments, the amino acid is selected from the group of branched-chain amino acids (BCAAs), including but not limited to isoleucine, leucine, and valine. In further embodiments, the amino acid is selected from the group of essential amino acids, including but not limited to histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. In yet further embodiments, the amino acid is selected from the group of conditionally essential amino acids, including but not limited to arginine, cysteine, glutamine, glycine, proline, ergothioneine, and tyrosine. According to certain embodiments, the conditionally essential amino acid is tyrosine. In yet further embodiments, the amino acid is selected from the group of non-essential amino acids, including but not limited to alanine, aspartic acid, asparagine, glutamic acid, serine, selenocysteine, and pyrrolysine. In yet further embodiments, the amino acid derivative is selected from the group of creatine, carnitine, β-alanine, taurine, β-hydroxy-β-methylbutyrate, L-arginine, omega-3 fatty acids, vitamin D, whey protein, BAIBA, and other protein extracts from animal, plant, or fermentation sources.

[0076]

[0086] According to exemplary aspects of these embodiments, the compositions can reduce fatigue, increase energy, improve mobility, and enhance alertness. In further embodiments, administration of the compositions of the present disclosure is cardioprotective. In further embodiments, administration of the compositions of the present disclosure enhances muscle contraction and muscle performance. In exemplary aspects of these embodiments, muscle performance is enhanced through increasing potassium (K+) transport into skeletal muscle. In further aspects, muscle performance is enhanced through increasing intracellular calcium (e.g., by activating ryanodine receptors (RyRs)).

[0077]

[0087] In certain aspects of the foregoing embodiments, wherein the composition comprises effective amounts of dileucine and paraxanthine, administration of paraxanthine and dileucine results in a synergistic increase in muscle size and / or function in the subject compared to administration of paraxanthine or dileucine alone.

[0078]

[0088] In certain further aspects of the foregoing embodiments, wherein the composition comprises effective amounts of dileucine and L-arginine, administration of L-arginine and dileucine results in a synergistic increase in muscle size and / or function in the subject compared to administration of L-arginine or dileucine alone.

[0079]

[0089] weight loss

[0001] According to certain embodiments, fat loss is promoted through inducing thermogenesis in a subject. According to exemplary implementations of such embodiments, the composition may also include one or more compounds selected from caffeine, green tea, capsaicin, Garcinia cambogia, yohimbine, catechol, epigallocatechin gallate (EGCG), catechin, and proanthocyanidins and octacosanol, and bitter orange.

[0080] According to further embodiments, fat loss is promoted through appetite suppression in a subject. In exemplary implementations of such embodiments, the composition can further comprise one or more compounds selected from fenugreek, glucomannan, Gymnema sylvestre, 5-HTP, Caralluma fimbriata, green tea extract, conjugated linoleic acid, Garcinia cambogia, and yerba mate.

[0081] According to yet further embodiments, fat loss is promoted through enhancing lipolysis in a subject. In exemplary implementations of such embodiments, the composition can further include one or more compounds selected from caffeine, green tea extract, L-carnitine, Garcinia cambogia (hydroxycitric acid), capsaicin, Korean ginseng, taurine, silk peptide, BAIBA, grains of paradise, ginger, and octacosanol.

[0082]

[0004] In certain embodiments, a composition of the present disclosure, when administered to a subject, increases the subject's resting energy expenditure compared to the subject's baseline level or compared to administration of a placebo. In certain embodiments, administration of a composition of the present disclosure increases the subject's resting energy expenditure by about 3% to about 30%. In further embodiments, administration of a composition of the present disclosure increases the subject's resting energy expenditure by about 5% to about 25%. In still further embodiments, administration of a composition of the present disclosure increases the subject's resting energy expenditure by about 8% to about 20%. In still further embodiments, administration of a composition of the present disclosure increases the subject's resting energy expenditure by about 10% or more.

[0083]

[0005] According to certain implementations, the disclosed methods further include restricting the subject's caloric intake. In exemplary implementations, the subject's fat loss is greater than the fat loss of a subject undergoing a comparable caloric restriction but not receiving the composition. According to further implementations, the ratio of fat loss to muscle loss in the subject is greater than the ratio of fat loss to muscle loss of a subject undergoing a comparable caloric restriction but not receiving the composition.

[0084]

[0006] Also disclosed herein is a method of suppressing appetite in a subject by administering to the subject a composition disclosed herein. In certain embodiments, administering the composition to a subject reduces the subject's appetite by between 5% and about 70%. In further embodiments, the subject's appetite is reduced by between about 10% and about 60%. In yet further embodiments, the subject's appetite is reduced by between about 20% and about 50%. In yet further embodiments, the subject's appetite is reduced by at least about 30%.

[0085] According to certain embodiments of the disclosed methods, the composition is administered in a therapeutically effective amount. In further embodiments, the composition is administered in a prophylactically effective amount.

[0008] In certain aspects, the present application discloses methods for promoting weight loss through the administration of an effective amount of one or more compositions disclosed herein. According to certain aspects, the administration of an effective amount of a composition disclosed herein is used for the following: treating diabetes; preventing, slowing, delaying or treating a condition or disorder selected from the group consisting of complications of diabetes; preventing, slowing, delaying or treating a metabolic disorder selected from the group consisting of type 1 diabetes, type 2 diabetes, impaired glucose tolerance (IGT), impaired fasting glucose (IFG), hyperglycemia, postprandial hyperglycemia, overweight, obesity, metabolic syndrome and gestational diabetes; or improving glycemic control and / or improving fasting plasma glucose, postprandial plasma glucose and / or glycosylation. or preventing, slowing, delaying or reversing the progression of impaired glucose tolerance (IGT), impaired fasting glucose (IFG), insulin resistance, and / or metabolic syndrome to type 2 diabetes; or preventing, slowing the progression of a condition or disorder selected from the group consisting of complications of diabetes, such as cataracts and micro- and macrovascular diseases, such as nephropathy, retinopathy, neuropathy, tissue ischemia, arteriosclerosis, myocardial infarction, stroke, and peripheral arterial occlusive disease. , slowing or treatment; or reducing body weight and / or body fat, or preventing weight and / or body fat gain, or promoting weight and / or body fat reduction; or preventing, slowing, slowing or treating diseases or conditions caused by the abnormal accumulation of ectopic fat; or maintaining and / or improving insulin sensitivity and / or treating or preventing hyperinsulinemia and / or insulin resistance; preventing, slowing, slowing or treating post-transplant onset diabetes (NODAT) and / or post-transplant metabolic syndrome (PTMS); preventing, slowing or reducing complications associated with NODAT and / or PTMS, such as micro- and macrovascular disease and events, graft rejection, infection and death; treating diabetes associated with cystic fibrosis, treating hyperuricemia and hyperuricemia-related conditions; treating or preventing kidney stones; preventing, slowing, slowing or treating hyponatremia in patients in need thereof.

[0086] Another aspect encompasses combination therapies for modulating fat storage, energy utilization, and / or weight loss in a subject. In exemplary embodiments, a combination for increasing energy utilization or reducing body fat or promoting weight loss may include combining the methods and compositions of the present disclosure with: For example, this may include combination with surgery or therapies such as drug therapy, gastric bypass, duodenal jejunal bypass, biliary pancreatic diversion, vertical sleeve gastrectomy, adjustable gastric banding, vertical interrupted gastroplasty, intragastric balloon therapy, gastric plication, Magenstrasse and Mill procedure, small intestinal transposition, bile outflow diversion, modulation of brown adipose tissue (e.g., controlled activation, enhanced differentiation, supplemental transplantation, etc.), drug administration, electrical stimulation of nerves innervating at least a portion of the gastrointestinal tract, therapies affecting circadian rhythm, modulation of bile acids, intestinal mucus production and metabolism, duodenal endoluminal barrier or similar gastrointestinal tract manipulation. For example, the composition dileucine can be administered to a subject prior to, in conjunction with, or after gastric bypass or other gastrointestinal or bariatric surgery.

[0087]

[0010] In certain aspects, administration of the compositions of the present disclosure is effective in preventing weight and / or body fat loss, or preventing weight and / or body fat gain, or facilitating weight and / or body fat loss; or preventing, slowing, delaying or treating diseases or conditions resulting from abnormal accumulation of liver fat; or maintaining and / or improving insulin sensitivity and / or treating or preventing hyperinsulinemia and / or insulin resistance.

[0088]

[0011] According to certain embodiments, administration of dileucine and paraxanthine results in a synergistic enhancement of weight management in a subject compared to administration of comparable doses of dileucine and / or paraxanthine alone.

[0089] According to further embodiments, administration of dileucine and L-arginine results in a synergistic enhancement of weight management in a subject compared to administration of comparable doses of dileucine and / or L-arginine alone. Cognitive function

[0013] Disclosed herein are methods of enhancing cognitive function in a subject, comprising administering to the subject a composition disclosed herein. In certain embodiments, enhanced cognitive function is measured by an increase in one or more of attention, information acquisition, information processing, working memory, short-term memory, long-term memory, anterograde memory, retrograde memory, memory retrieval, discrimination learning, decision-making, inhibitory response control, attentional set switching, delayed (reward) reinforcement learning, reversal learning, temporal integration of spontaneous behavior, processing speed, reasoning, problem solving, and / or social cognition.

[0090]

[0014] In certain embodiments, administration of a composition of the present disclosure increases working memory. In a further embodiment, administration of the compositions of the present disclosure increases alertness.

[0016] According to certain embodiments, the composition of the disclosed method for enhancing cognitive function further comprises tyrosine, N-acetyltyrosine, taurine, huperzine A, acetyl-l-carnitine, CDP choline, α-GPC, choline bitrate, choline citrate, B12, caffeine, methylliberin, theacrine, paraxanthine, theobromine, ashwagandha, Rhodiola rosea, lutein, zeaxanthin, fish oil, creatine, ginseng, Yamabushitake, niacin, Atractylodes gracilis, theanine, B vitamins, GABA, sulbutiamine, vinpocetine, adenosine triphosphate, inositol, enriched arginine silicate, nitrates, electrolytes, hesperidin and hesperidin derivatives, and / or bacopa.

[0091]

[0017] According to certain embodiments, administration of dileucine and paraxanthine results in a synergistic enhancement of cognitive function in a subject compared to administration of comparable doses of dileucine and / or paraxanthine alone.

[0092]

[0018] According to a further embodiment, administration of dileucine and L-arginine results in a synergistic enhancement of cognitive function in a subject compared to administration of comparable doses of dileucine and / or L-arginine alone.

[0093]

[0019] In certain embodiments, the subject is experiencing age-related cognitive decline. In exemplary implementations, administration of the composition to a subject increases BDNF levels in the subject. According to certain embodiments, administration of the composition to a subject increases brain-derived neurotrophic factor (BDNF) levels in the subject. In exemplary implementations, BDNF levels are increased by about 5% to about 40%. In further embodiments, BDNF levels are increased by at least about 15%. In further embodiments, administration of the composition to a subject increases other neurotrophic factors, such as neuron growth factor (NGF). In still further embodiments, administration of the composition to a subject increases mTOR levels in the CNS. Strengthening immune function

[0020] Also disclosed herein are methods for enhancing immune function and / or inhibiting inflammation by administering a composition of the present disclosure to a subject in need thereof. In particular, the compositions of the present disclosure can be used to enhance immune function in that they enhance the ability to respond to acute pathogenic stimuli. Furthermore, when administered according to the methods of the present disclosure, the compositions of the present disclosure enhance a protective immune response against autologous triggers, such as exogenous pathogens or neoplastic cells. Thus, the compositions of the present disclosure can be used as prophylactic agents, for example, to avoid infectious diseases or to reduce the severity of infectious diseases or other immune-related diseases.

[0094] In certain embodiments, the compositions of the present disclosure are administered to a subject at risk of contracting an infectious disease. In exemplary implementations of such embodiments, the compositions may be administered in a prophylactically effective amount.

[0095] In further embodiments, the compositions of the present disclosure may be administered to a subject suffering from an infectious disease or condition. In exemplary implementations of such embodiments, the compositions of the present disclosure may be administered in a therapeutically effective amount.

[0096] In certain embodiments, the composition further comprises one or more additional active agents selected from the list consisting of: cyclosporine, tacrolimus, rapamycin, omega-3 fatty acids, curcumin, S-adenosylmethionine, zinc, green tea extract, frankincense (Boswellia serrata resin), capsaicin, cat's claw (plants of the genus Uncaria, such as Uncaria tomentosa and Uncaria guianensis), Schizonepeta tenuifolia, pomegranate, Moringa oleifera, Ecklonia cava, limonene, sniphyllum, sulforaphane, Angelica gigas, Ascophyllum nodosum, Scutellaria baicalensis, celery seed extract, sesamin, feverfew, taurine, rosmarinic acid, Evodia rutaecarpa, green tea catechins, punicalagins, Artemisia Iwayomogi, Pyrroloquinoline Quinone, N-Acetyl Cysteine, King Oyster Mushroom, Methylsulfonylmethane, Alpha-Lipoic Acid, Pine Pollen, Sophora flavescens, Ophiopogon japonicus, Stephania tetrandra, Crataegus pinnatifida, Grape Seed Extract, Bladderwrack, Paederia foetida, Benfotiamine, Rubus coreanus, Punicic Acid, Sea Buckthorn, Hibiscus rosasinensis, Phellodendron amurense, Resveratrol, Quercetin, Rooibos, Olive Leaf Extract, Pterostilbene, Eucommia ulmoides, Diindolylmethane, Anatabine, Serrapeptase, Pelargonidin, Watercress, Astaxanthin, Piceatannol, Fish Oil, Glutathione, Orthosiphon stamineus, Aronia melanocarpa, Blueberry, Tripterygium wilfordii, Boerhaavia diffusa, whey protein, bromelain, Panax ginseng, Aloe vera, cocoa extract, nettle, garlic, Centella asiatica, Astragalusmembranaceus, Dendrobium, Vitamin C, Spirulina, Berberine, Ganoderma lucidum, Vitamin C, Vitamin D, Vitamin E, Lutein, Pau d'Arco, AHCC, Rhodiola, Ashwagandha, Shiitake, Maitake, Coriolus versicolor, Monolaurin, Lysine, Ergothioneine, Medium Chain Triglycerides (MCT) and Butyrate.

[0097]

[0024] According to certain embodiments, administration of dileucine and paraxanthine results in a synergistic enhancement of immune function in a subject compared to administration of comparable doses of dileucine and / or paraxanthine alone.

[0098]

[0025] According to a further embodiment, administration of dileucine and L-arginine results in a synergistic enhancement of immune function in a subject compared to administration of comparable doses of dileucine and / or L-arginine alone. anti-inflammatory Further disclosed herein is a method of inhibiting inflammation in a subject in need thereof, comprising administering to the subject a composition disclosed herein, comprising administering to the subject an amount of dileucine from about 10 mg to about 5,000 mg; a) paraxanthine in an amount from about 2 mg to about 800 mg, or b) L-arginine in an amount from about 500 mg to about 6,000 mg; The method comprises administering a therapeutically effective amount of a composition comprising:

[0099] In certain embodiments, paraxanthine is present in the composition in an amount from about 20 mg to about 600 mg. In further embodiments, paraxanthine is present in the composition in an amount from about 50 mg to about 400 mg.

[0100] In certain embodiments, the one or more additional active substances are anti-inflammatory agents. Disclosed anti-inflammatory agents include agents that exert their anti-inflammatory effects by inhibiting prostaglandins (e.g., targeting COX-2), increasing macrophage-mediated phagocytosis (e.g., resolvins), suppressing cytokine-driven inflammation (e.g., glucocorticoids), suppressing cytokine-driven inflammation, inhibiting cytokines, inhibiting histone deacetylation, inhibiting kinases, stimulating PPARs, and / or inhibiting proteases.

[0101]

[0029] Anti-inflammatory agents include, but are not limited to, aspirin, ibuprofen, naproxen, hyssop, ginger, turmeric, helenalin, cannabichromene, rofecoxib, celecoxib, paracetamol (acetaminophen), sirolimus (rapamycin), dexamethasone, dipyridamole, alfuzosin, statins and glitazones.

[0102] In further embodiments, the steroidal anti-inflammatory agent is a non-steroidal anti-inflammatory agent or a combination thereof. In some embodiments, the anti-inflammatory agent includes clobetasol, alclofenac, alclometasone dipropionate, algestone acetonide, α-amylase, amcinafal, amcinafide, amfenac sodium, amiprilose hydrochloride, anakinra, anilolac, anitrazafen, apazone, balsalazide disodium, bendazac, benoxaprofen, benzydamine hydrochloride, bromelain, broperamol, budesonide, carprofen, cycloprofen, synthazone, criprofen, propionate, thiazol-3-one ... Clobetasol nitrate, clobetasone butyrate, clopirac, cloticasone propionate, cormetasone acetate, cortodoxone, deflazacort, desonide, desoximetasone, dexamethasone, dexamethasone acetate, dexamethasone dipropionate, diclofenac potassium, diclofenac sodium, diflorasone acetate, diflumidone sodium, diflunisal, difluprednate, diphthalone, dimethyl sulfoxide, drocinonide, endrizone, enlimomab, enolicam sodium, epirizole, etodora ak, etofenamate, felbinac, fenamol, fenbufen, fenclofenac, fenclorac, fendosal, fenpiparone, fentiazac, flavazalon, fluazacort, flufenamic acid, flumisole, flunisolide acetate, flunixin, flunixin meglumine, fluocortin butyl, fluorometholone acetate, fluquazone, flurbiprofen, fluretofen, fluticasone propionate, furaprofen, flobufen, halcinonide, halobetasol propionate, halopredone acetate, ibuprofen Bufenac, ibuprofen, ibuprofen aluminum, ibuprofen piconol, ilonidap, indomethacin, indomethacin sodium, indoprofen, indoxol, intrazole, isoflupredone acetate, isoxepac, isoxicam, ketoprofen, lofemizole hydrochloride, lomoxicam, loteprednol etabonate, meclofenamate sodium, meclofenamic acid, meclorisone dibutyrate, mefenamic acid, mesalamine, meseclazone,Methylprednisolone suleptanate, momiflumate, nabumetone, naproxen, naproxen sodium, naproxol, nimazone, olsalazine sodium, orgotein, orpanoxin, oxaprozin, oxyphenbutazone, paranyline hydrochloride, pentosan polysulfate sodium, phenbutazone sodium glycerate, pirfenidone, piroxicam, piroxicam cinnamate, piroxicam olamine, pirprofen, prednazate, priferon, prodolate, proquazone, proxazole, proxazole citrate, rimexolone, romazarito, sarcorex, salnacedin, salsalate , sanguinarium chloride, seclazone, celmetasin, sudoxicam, sulindac, suprofen, talmetasin, talniflumate, talosalate, tebufelone, tenidap, tenidap sodium, tenoxicam, tesicam, tesimide, tetridamine, tiopinac, tixocortol pivalate, tolmetin, tolmetin sodium, triclonide, triflumidate, zidometacin, zomepirac sodium, aspirin (acetylsalicylic acid), salicylic acid, corticosteroids, glucocorticoids, tacrolimus, pimecorlimus, prodrugs thereof, codrugs thereof, and combinations thereof. Anti-inflammatory agents may also be biological inhibitors of pro-inflammatory signaling molecules, such as antibodies against the biological inflammatory signaling molecules.

[0103] According to certain embodiments, administration of dileucine and paraxanthine results in synergistic inhibition of inflammation in a subject compared to administration of comparable doses of dileucine and / or paraxanthine alone.

[0104] According to a further embodiment, administration of dileucine and L-arginine results in synergistic inhibition of inflammation in a subject compared to administration of comparable doses of dileucine and / or L-arginine alone.

[0105] In certain embodiments, the subject is at risk of developing an inflammatory disease or condition. In further embodiments, the subject has been diagnosed with an inflammatory disease or condition. In exemplary implementations, the subject has been diagnosed with diabetes, Crohn's disease, rheumatoid arthritis, fibromyalgia, systemic lupus erythematosus, glomerulonephritis, scleroderma, or multiple sclerosis.

[0106] In still further embodiments, the one or more additional ingredients are selected from the group consisting of omega-3 fatty acids, vitamin D, vitamin B, protein, selenium, rapidly digestible carbohydrates such as sugars, vitamin K, calcium, vitamin A, Ashwagandha (Withania somnifera), acetylcholine, acetyl-L-carnitine, tyrosine, N-acetyl-L-tyrosine, ergothioneine, tryptophan, 5-HTP, arginine, citrulline, norvaline, GABA, dopa (Mucuna pruriens), Kanna (serotonin), L-theanine, phosphatidylcholine, α-GPC (L-α-glycerylphosphorylcholine), citicoline (cytidine diphosphate choline (CPD choline)), choline bitartrate, Bacopa Monnieri, phosphatidylserine, pilocarpine, and cevimeline, Amburana cearensis, Lippia sidoides, Paullinia cupana, Plathymiscium floribundum, tetrahydrocurcumin and Solanum asperum. Cardiovascular health

[0035] Further disclosed herein are methods of enhancing cardiovascular health and / or treating cardiovascular diseases or conditions by administering a composition disclosed herein. In certain embodiments, enhancing cardiovascular health is achieved by enhancing (improving) the subject's blood lipid profile. As used herein, "enhancing the serum lipid profile" means reducing serum total and / or LDL cholesterol and triacylglycerol concentrations, and increasing the ratio of HDL cholesterol to LDL cholesterol.

[0107] For example, a subject can be identified as needing treatment for a disorder (e.g., a disorder associated with high serum total and / or LDL cholesterol and triacylglycerol levels and a low HDL cholesterol to LDL cholesterol ratio) based on a previous diagnosis by a skilled practitioner, and then receive treatment for that disorder. It is contemplated that the identification, in one embodiment, can be performed by a person different from the person making the diagnosis. It is also contemplated that, in a further embodiment, the administration can be performed by a person who subsequently performed the administration.

[0108]

[0037] In certain aspects, disclosed herein are methods of enhancing the serum lipid profile in a subject through administration of an effective amount of one or more of the compositions disclosed herein.

[0109]

[0038] The present application discloses a method for enhancing the serum lipid profile in a subject, the method comprising administering to the subject an effective amount of a composition disclosed herein.

[0110]

[0039] In another aspect, a method for preventing or treating a cardiovascular condition is provided, wherein the cardiovascular condition includes symptoms of atherosclerotic plaque formation. The method includes administering a therapeutically effective amount of a composition disclosed herein to a subject in need of prevention or treatment of the cardiovascular condition. Cardiovascular conditions include, for example, coronary artery disease, coronary microvascular disease, stroke, carotid artery disease, peripheral artery disease, and chronic kidney disease. The method can include further slowing the progression of atherosclerotic plaque formation. The method can further include administering to the subject one or more additional therapeutic agents for the prevention or treatment of the cardiovascular condition.

[0111]

[0040] In another aspect, a method for treating metabolic syndrome is provided. The method includes administering a therapeutically effective amount of a composition disclosed herein to a subject in need of metabolic syndrome treatment. The method can further include reducing one or more risk factors associated with metabolic syndrome, such as one or more of abdominal obesity, hyperglycemia, dyslipidemia, and hypertension. The method can further include administering one or more additional agents to the subject for the prevention or treatment of metabolic syndrome.

[0112] In another aspect, a method for delaying or slowing the progression of atherosclerosis is provided, comprising administering to a subject in need thereof an amount of dileucine in an amount of from about 10 mg to about 5,000 mg, a) paraxanthine in an amount from about 2 mg to about 800 mg, or b) L-arginine in an amount from about 500 mg to about 6,000 mg; The method comprises administering a therapeutically effective amount of a composition comprising:

[0113]

[0042] In certain aspects, the composition further comprises one or more additional active ingredients for further enhancing the serum lipid profile in a subject. In certain embodiments, the one or more additional active ingredients are amino acids. According to certain embodiments, the amino acid is selected from the group of branched-chain amino acids (BCAAs), including, but not limited to, isoleucine, leucine, and valine. In further embodiments, the amino acid is selected from the group of essential amino acids, including, but not limited to, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. In still further embodiments, the amino acid is selected from the group of conditionally essential amino acids, including, but not limited to, arginine, cysteine, glutamine, glycine, proline, and tyrosine. According to certain embodiments, the conditionally essential amino acid is tyrosine. In still further embodiments, the amino acid is selected from the group of non-essential amino acids, including, but not limited to, alanine, aspartic acid, asparagine, glutamic acid, serine, selenocysteine, and pyrrolysine. In still further embodiments, the amino acid derivative is selected from the group of creatine, carnitine, creatinol, β-alanine, taurine, β-hydroxy-β-methylbutyrate, L-arginine, omega-3 fatty acids, vitamin D, nonsteroidal anti-inflammatory drugs (NSAIDs), whey protein, and other protein extracts derived from animal, plant, or fermentation sources.

[0114] In still further embodiments, the one or more additional ingredients are selected from the group consisting of omega-3 fatty acids, vitamin D, vitamin B, protein, selenium, rapidly digestible carbohydrates such as sugars, vitamin K, calcium, vitamin A, ashwagandha (Withania somnifera), acetylcholine, acetyl-L-carnitine, tyrosine, N-acetyl-L-tyrosine, ergothioneine, tryptophan, 5-HTP, arginine, citrulline, norvaline, GABA, dopa (Mucuna pruriens), kanna (serotonin), L-theanine, phosphatidylcholine, α-GPC (L-α-glycerylphosphorylcholine), citicoline (cytidine diphosphate choline (CPD choline)), choline bitartrate, Bacopa Monnieri, phosphatidylserine, pilocarpine and cevimeline, Amburana cearensis, Lippia sidoides, Paullinia cupana, Plathymiscium floribundum, tetrahydrocurcumin and Solanum asperum.

[0115]

[0044] According to certain embodiments, administration of dileucine and paraxanthine results in a synergistic enhancement of cardiovascular health in a subject compared to administration of comparable doses of dileucine and / or paraxanthine alone.

[0116]

[0045] According to a further embodiment, administration of dileucine and L-arginine results in a synergistic enhancement of cardiovascular health in a subject compared to administration of comparable doses of dileucine and / or L-arginine alone. Increased blood flow

[0046] Also disclosed herein are methods for enhancing blood flow in a subject by administering to the subject a composition disclosed herein. In certain implementations, the disclosed methods for enhancing blood flow are useful in conjunction with athletic training or performance, as increased blood flow to muscles during physical activity can result in increased performance. In further embodiments, the disclosed methods for increasing blood flow are useful for treating diseases or conditions characterized by reduced blood flow to a tissue or organ system. For example, disclosed herein are methods for promoting blood flow in an area of ​​a subject experiencing or at risk of developing ischemia, such as ischemia resulting from surgery, burns, transplants, peripheral vascular disease, amputation, coronary artery disease, stroke, thrombosis, clots, chronic vascular occlusion or vascular disorders (e.g., secondary to diabetes, hypertension, or peripheral vascular disease), cerebral ischemia, or ischemia occurring during or following a wound. The provided methods are useful in the treatment of a variety of diseases and conditions, including, but not limited to, treatment of donor organs before and after transplantation; reattachment of severed limbs, body parts, or soft tissues; pulmonary hypertension (adult or neonatal); sickle cell disease; neointimal hyperplasia or restenosis (following angioplasty or stent placement); primary burn care (performed before performing a skin graft); renal disease (e.g., increasing renal circulation); pre-eclampsia; erectile dysfunction; asthma or adult respiratory distress syndrome.

[0117]

[0047] According to certain embodiments, administration of dileucine and paraxanthine results in a synergistic enhancement of blood flow in a subject compared to administration of comparable doses of dileucine and / or paraxanthine alone.

[0118] According to a further embodiment, administration of dileucine and L-arginine results in a synergistic enhancement of blood flow in a subject compared to administration of comparable doses of dileucine and / or L-arginine alone. Administration route Administration of the compositions of the present disclosure to a subject can include any method of providing a pharmaceutical and / or nutraceutical preparation to a subject. Such methods are well known to those skilled in the art and include, but are not limited to, oral administration, transdermal administration, administration by inhalation, intranasal administration, topical administration, intravaginal administration, ocular administration, intraaural administration, intracerebral administration, rectal administration, sublingual administration, intradermal administration, buccal administration, and parenteral administration, including injections, such as intravenous, intraarterial, intramuscular, and subcutaneous administration. Administration can be continuous or intermittent. In various aspects, the preparations can be administered therapeutically, i.e., to treat an existing disease or condition. In further various aspects, the preparations can be administered prophylactically, i.e., to prevent a disease or condition. According to further embodiments, the compositions of the present disclosure can be administered as a beverage, functional food, and / or medicinal food, as described above.

[0119]

[0050] Various aspects and embodiments of the present invention are defined by the following numbered clauses: Item 1. A composition comprising paraxanthine and dileucine. Item 2. The composition of item 1, wherein paraxanthine is present in an amount from about 2 mg to about 800 mg. Item 3. The composition of item 2, wherein paraxanthine is present in an amount from about 20 mg to about 600 mg. Item 4. The composition of item 3, wherein paraxanthine is present in an amount from about 50 mg to about 400 mg. Item 5. The composition of any one of items 1 to 4, wherein the dileucine is present in an amount from about 200 mg to about 5,000 mg. Item 6. The composition of item 5, wherein the dileucine is present in an amount from about 500 mg to about 3,000 mg. Item 7. A composition comprising dileucine and L-arginine. Item 8. The composition of item 7, wherein the dileucine is present in an amount from about 10 mg to about 5,000 mg. Item 9. The composition of item 8, wherein the dileucine is present in an amount from about 25 mg to about 2,500 mg. Item 10. The composition of any one of items 7 to 9, wherein the L-arginine is present in an amount of about 500 mg to about 6,000 mg. Item 11. The composition of item 10, wherein the L-arginine is present in an amount of about 1,000 mg to about 3,000 mg. Item 12. The composition of any one of items 7 to 11, wherein the L-arginine is in the form of free L-arginine, a salt, a bound arginine silicate complex and / or arginine alpha-ketoglutarate. Item 13. The composition of any one of items 1 to 12, which is a dietary supplement. Item 14. The composition of any one of items 1 to 13, which is a powder. Clause 15. The composition of any one of clauses 1 to 13, which is a functional food. Item 16. The composition of item 15, wherein the functional food is a beverage, a nutritional bar, a yogurt, or a cereal. Item 17. The composition of item 16, which is a beverage. Item 18. The composition of any one of items 1 to 12, which is a sublingual spray. Item 19. The composition of any one of items 1 to 12, further comprising a nutraceutical acceptable carrier. Clause 20. The composition of clause 19, wherein the nutraceutical acceptable carrier is a capsule. Clause 21. A method for increasing muscle strength, muscle size and / or muscle function, comprising administering to a subject the composition of any one of clauses 1 to 20. Clause 22. The method of clause 21, wherein the composition further comprises one or more compounds selected from the list consisting of isoleucine, leucine and valine, histidine, lysine, methionine, phenylalanine, threonine, tryptophan, valine, creatine, cysteine, glutamine, glycine, proline, tyrosine, carnitine, beta-alanine, taurine, beta-hydroxy-beta-methylbutyrate, omega-3 fatty acids, vitamin D, whey protein, and other protein extracts from animal, plant, or fermentation sources. Clause 23. The method of clause 21 or 22, wherein the composition administered is the composition of any one of clauses 1 to 9, and wherein administration of dileucine and paraxanthine in the composition results in a synergistic increase in muscle strength, muscle size and / or muscle function in the subject compared to administration of comparable doses of dileucine and / or paraxanthine alone. Clause 24. The method of clause 21 or 22, wherein the composition administered is the composition of any one of clauses 10 to 19, and wherein administration of dileucine and L-arginine in the composition results in a synergistic increase in muscle strength, muscle size, and / or muscle function in the subject compared to administration of comparable doses of dileucine and / or L-arginine alone. Clause 25. A method of increasing exercise capacity in a subject in need thereof, comprising administering to the subject an effective amount of the composition of any one of clauses 1 to 20. Clause 26. The method of clause 25, wherein the composition administered is the composition of any one of clauses 1 to 9, and wherein administration of dileucine and paraxanthine in the composition results in a synergistic increase in exercise endurance in the subject compared to administration of comparable doses of dileucine and / or paraxanthine alone. Clause 27. The method of clause 25, wherein the composition administered is the composition of any one of clauses 10 to 19, and wherein administration of dileucine and L-arginine in the composition results in a synergistic increase in exercise performance in the subject compared to administration of comparable doses of dileucine and / or L-arginine alone. Clause 28. A method of promoting weight loss in a subject, comprising administering to the subject a composition of any one of clauses 1-20. Clause 29. The method of clause 28, wherein weight loss is promoted through inducing thermogenesis in the subject. Clause 30. The method of clause 29, wherein the composition further comprises one or more compounds selected from the list consisting of caffeine, green tea, capsaicin, garcinia cambogia, yohimbine, and bitter orange. Clause 31. The method of clause 28, wherein weight loss is promoted through appetite suppression in the subject, and administration of the composition to the subject suppresses appetite in the subject by at least about 30%. Clause 32. The method of clause 28, wherein weight loss is promoted through enhancing lipolysis in said subject. Clause 33. The method of clause 28, wherein administering the composition to the subject decreases the respiratory quotient in the subject by at least about 10%. Clause 34. The method of clause 28, wherein resting energy expenditure in said subject is increased by at least about 15%. Item 35. The method of item 32, wherein the composition further comprises one or more compounds selected from the list consisting of caffeine, green tea extract, L-carnitine, Garcinia cambogia (hydroxycitric acid), capsaicin, Korean ginseng, taurine, silk peptide, catechol, epigallocatechin gallate (EGCG), catechin, proanthocyanidin, and octacosanol. Clause 36. The method of clause 28, further comprising restricting the caloric intake of the subject, wherein the subject loses more weight than a subject on a comparable calorie restriction who is not administered the composition, and the subject loses more fat to muscle than a subject on a comparable calorie restriction who is not administered the composition. Clause 37. The method of clause 28, wherein the subject is not administered caffeine. Clause 38. A method of suppressing appetite in a subject, comprising administering to the subject a composition of any one of clauses 1-20. Clause 39. The method of clause 38, wherein administering the composition reduces appetite in the subject by at least about 30%. Clause 40. The method of clause 38, wherein the subject is not administered caffeine. Clause 41. A method of promoting fat loss in a subject, comprising administering to the subject a composition of any one of clauses 1 to 20. Clause 42. The method of clause 41, wherein the subject is not administered caffeine. Clause 43. The method of clause 41, wherein fat loss is promoted through inducing thermogenesis in the subject. Item 44. The method of item 43, wherein the composition further comprises one or more compounds selected from the list consisting of caffeine, green tea, capsaicin, Garcinia cambogia, yohimbine, catechol, EGCG, catechin, and proanthocyanidins and octacosanol, and bitter orange. Clause 45. The method of clause 41, wherein fat loss is promoted through appetite suppression in said subject. Clause 46. The method of clause 45, wherein administering the composition to the subject suppresses appetite in the subject by at least about 30%. Clause 47. The method of clause 41, wherein administering the composition to the subject decreases the respiratory quotient in the subject by at least about 10%. Clause 48. The method of clause 45, wherein the composition further comprises one or more compounds selected from the list consisting of fenugreek, glucomannan, Gymnema sylvestre, 5-HTP, Caralluma fimbriata, green tea extract, conjugated linoleic acid, Garcinia cambogia, and yerba mate. Clause 49. The method of clause 41, wherein fat loss is promoted through enhancing lipolysis in said subject. Item 50. The method of item 49, wherein the composition further comprises one or more compounds selected from the list consisting of caffeine, green tea extract, L-carnitine, Garcinia cambogia (hydroxycitric acid), capsaicin, ginseng, taurine, silk peptide, and octacosanol. Clause 51. The method of clause 41, further comprising restricting the subject's caloric intake. Clause 52. The method of clause 51, wherein the fat loss in the subject is greater than the fat loss in a subject undergoing comparable caloric restriction but not receiving the composition. Clause 53. The method of clause 51, wherein the ratio of fat loss to muscle loss in the subject is greater than the ratio of fat loss to muscle loss in a subject undergoing comparable calorie restriction but not receiving the composition. Clause 54. A method of enhancing attention in a subject in need thereof, comprising administering a composition according to any one of clauses 1 to 20. Clause 55. A method of enhancing working memory in a subject in need thereof, comprising administering to said subject a composition of any one of clauses 1 to 20. Clause 56. A method of enhancing cognitive performance in a subject, comprising administering a composition of any one of clauses 1 to 20. Paragraph 57. The method of paragraph 56, wherein the enhanced cognitive function is measured by an increase in one or more of attention, information acquisition, information processing, working memory, short-term memory, long-term memory, anterograde memory, retrograde memory, memory recall, discrimination learning, decision-making, inhibitory response control, attentional set switching, delayed reward reinforcement learning, reversal learning, temporal integration of spontaneous behavior, processing speed, reasoning, problem solving, and / or social cognition. Clause 58. The method of clause 56 or 57, wherein the composition administered is a composition of any one of clauses 1 to 9, and wherein administration of dileucine and paraxanthine in the composition results in a synergistic enhancement of cognitive function in the subject compared to administration of comparable doses of dileucine and / or paraxanthine alone. Clause 59. The method of clause 56 or 57, wherein the composition administered is the composition of any one of clauses 10 to 19, and wherein administration of dileucine and L-arginine in the composition results in a synergistic enhancement of cognitive function in the subject compared to administration of comparable doses of dileucine and / or L-arginine alone. Clause 60. A method of treating an inflammatory disease or condition in a subject in need thereof, comprising administering to the subject a composition comprising the composition of any one of clauses 1 to 20. Clause 61. The method of clause 60, wherein the composition further comprises an additional anti-inflammatory agent. Clause 62. The method of clause 61, wherein the second anti-inflammatory agent exerts an anti-inflammatory effect by inhibiting prostaglandins, increasing macrophage-mediated phagocytosis, suppressing cytokine-driven inflammation, inhibiting cytokines, inhibiting histone deacetylation, inhibiting kinases, stimulating PPARs, and / or inhibiting proteases. Clause 63. The method of clause 61, wherein the additional anti-inflammatory agent is selected from aspirin, ibuprofen, naproxen, hyssop, ginger, turmeric, helenalin, cannabichromene, rofecoxib, celecoxib, paracetamol (acetaminophen), sirolimus (rapamycin), dexamethasone, dipyridamole, alfuzosin, a statin, and a glitazone. Clause 64. A method of enhancing joint health in a subject in need thereof, comprising providing to the subject a composition comprising the composition of any one of clauses 1 to 20. Clause 65. The method of clause 64, wherein the subject has been diagnosed with an inflammatory joint disease or condition. Clause 66. The method of clause 64, wherein the subject is at risk of developing an inflammatory joint disease or condition. Clause 67. A method of treating an inflammatory joint disease, comprising administering to a subject a composition comprising the composition of any one of clauses 1 to 20. Clause 68. The method of clause 67, wherein the composition is administered in a therapeutically effective amount. Clause 69. The method of clause 67, wherein the composition is administered in a prophylactically effective amount. Paragraph 70. A method of enhancing immune function in a subject, comprising: A method comprising the step of providing to the subject a composition comprising the composition of any one of items 1 to 20. Clause 71. The method of clause 70, wherein the composition administered is a composition of any one of clauses 1 to 9, and wherein administration of dileucine and paraxanthine in the composition results in a synergistic enhancement of immune function in the subject compared to administration of comparable doses of dileucine and / or paraxanthine alone. Clause 72. The method of clause 70, wherein the composition administered is the composition of any one of clauses 10 to 19, and wherein administration of dileucine and L-arginine in the composition results in a synergistic enhancement of immune function in the subject compared to administration of comparable doses of dileucine and / or L-arginine alone. Item 73. The composition comprises cyclosporine, tacrolimus, rapamycin, omega-3 fatty acids, curcumin, S-adenosylmethionine, zinc, green tea extract, frankincense (Boswellia serrata resin), capsaicin, cat's claw (plants of the genus Uncaria, such as Uncaria tomentosa and Uncaria guianensis), Schizonepeta tenuifolia, pomegranate, Moringa oleifera, Ecklonia cava, limonene, sniphyllum, sulforaphane, Angelica gigas, Ascophyllum nodosum, Scutellaria baicalensis, celery seed extract, sesamin, feverfew, taurine, rosmarinic acid, Evodia rutaecarpa, green tea catechins, punicalagins, Artemisia Iwayomogi, Pyrroloquinoline Quinone, N-Acetyl Cysteine, King Oyster Mushroom, Methylsulfonylmethane, Alpha-Lipoic Acid, Pine Pollen, Sophora flavescens, Ophiopogon japonicus, Stephania tetrandra, Crataegus pinnatifida, Grape Seed Extract, Bladderwrack, Paederia foetida, Benfotiamine, Rubus coreanus, Punicic Acid, Sea Buckthorn, Hibiscus rosasinensis, Phellodendron amurense, Resveratrol, Quercetin, Rooibos, Olive Leaf Extract, Pterostilbene, Eucommia ulmoides, Diindolylmethane, Anatabine, Serrapeptase, Pelargonidin, Watercress, Astaxanthin, Piceatannol, Fish Oil, Glutathione, Orthosiphon stamineus, Aronia melanocarpa, Blueberry, Tripterygium wilfordii, Boerhaavia diffusa, whey protein, bromelain, Panax ginseng, Aloe vera, cocoa extract, nettle, garlic, Centella asiatica, Astragalus membranaceus, Dendrobium, vitamin C, spirulina, berberine, Ganoderma73. The method of any one of clauses 70 to 72, further comprising one or more compounds selected from the list consisting of: lucidum, vitamin C, vitamin D, vitamin E, lutein, leucine, dileucine, trileucine, tetraleucine, pau d'arco, AHCC, Rhodiola rosea, ashwagandha, shiitake, maitake, coriolus versicolor, monolaurin, lysine, ergothioneine, medium chain triglycerides (MCT), and butyrate. Clause 74. A method of enhancing cardiovascular health in a subject, comprising providing to the subject a composition comprising the composition of any one of clauses 1 to 20. Clause 75. The method of clause 74, wherein the composition administered is a composition of any one of clauses 1 to 9, and wherein administration of dileucine and paraxanthine in the composition results in a synergistic enhancement of cardiovascular health in the subject compared to administration of comparable doses of dileucine and / or paraxanthine alone. Clause 76. The method of clause 74, wherein the composition administered is the composition of any one of clauses 10 to 19, and wherein administration of dileucine and L-arginine in the composition results in a synergistic enhancement of cardiovascular health in the subject compared to administration of comparable doses of dileucine and / or L-arginine alone. Clause 77. A method of enhancing blood flow in a subject, comprising providing to the subject a composition comprising the composition of any one of clauses 1 to 20. Clause 78. The method of clause 77, wherein the composition administered is a composition of any one of clauses 1 to 9, and wherein administration of dileucine and paraxanthine in the composition results in a synergistic enhancement of blood flow in the subject compared to administration of comparable doses of dileucine and / or paraxanthine alone. Clause 79. The method of clause 77, wherein the composition administered is the composition of any one of clauses 10 to 19, and wherein administration of dileucine and L-arginine in the composition results in a synergistic enhancement of blood flow in the subject compared to administration of comparable doses of dileucine and / or L-arginine alone. Clause 80. A method for increasing exercise endurance in a subject, comprising administering to the subject an effective amount of a composition described in any one of clauses 1 to 20. Clause 81. The method of clause 80, wherein the composition administered is a composition of any one of clauses 1 to 9, and wherein administration of dileucine and paraxanthine in the composition results in a synergistic increase in exercise endurance in the subject compared to administration of comparable doses of dileucine and / or paraxanthine alone. Clause 82. The method of clause 80, wherein the composition administered is the composition of any one of clauses 10 to 19, and wherein administration of dileucine and L-arginine in the composition results in a synergistic increase in exercise endurance in the subject compared to administration of comparable doses of dileucine and / or L-arginine alone. [Example]

[0120] The following examples are presented with the intent of providing those of ordinary skill in the art with a complete disclosure and description of some examples of how to make and evaluate the compounds, compositions, articles, devices and / or methods claimed herein, and are intended to be purely exemplary of the invention and are not intended to limit the scope of what the inventors regard as their invention. However, those of ordinary skill in the art should, in light of the present disclosure, understand that many changes can be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the spirit and scope of the invention. Animals and experimental design Eight 8-week-old male Swiss Albino mice were housed in groups of eight per experimental group in an animal room under a 12:12-h light / dark cycle at a constant temperature (22 ± 3°C) and humidity (30%–70%). They were fed a standard laboratory diet (Purina 5L79, Rat and Mouse 18% protein; PMI Nutrition International, Brentwood, MO, USA). Distilled water was available ad libitum. All animal experiments were reviewed and approved by the Institutional Animal Ethical Committee (IAEC) of Radiant Research Services Pvt. Ltd. (Bangalore, India). All studies were conducted in accordance with the committee's guidelines for conducting and supervising animal experiments (CPCSEA registration number 1803 / PO / RcBi / S / 2015 / CPCSEA).

[0121] After one week of acclimation, animals were randomly assigned to different groups based on body weight (n = 8 per group for each test) and received oral treatment once daily at approximately the same time (± 1 h) for 28 consecutive days. Treatments included: (1) vehicle control, (2) paraxanthine, (3) dileucine, (4) paraxanthine + dileucine, (5) L-arginine, (6) L-arginine + dileucine, (7) L-citrulline, and (8) L-citrulline + dileucine. Doses administered to mice were calculated using the U.S. Food and Drug Administration method for human equivalent doses (HEDs), assuming a human weight of 60 kg. The following HEDs were used in this study: dileucine 2,000 mg (RAMPS®, Ingenious Ingredients, LP, Lewisville, TX, USA; 411 mg per kg of mouse body weight), paraxanthine 100 mg (ENFINITY™, Ingenious Ingredients, LP, Lewisville, TX, USA; mouse dose: 20.5 mg per kg of mouse body weight / day); L-arginine 3,000 mg (Nanjing Nutrabuilding Bio-tech Co., LTD., No. 270 Jiqingmen Street, Suning Huigu, Building E6, Room 2105, Nanjing, China, 210017; 616.55 mg per kg of mouse body weight), L-citrulline 3,000 mg (Nanjing Nutrabuilding Bio-tech Co., LTD., No. 270 Jiqingmen Street, Suning Huigu, Building E6, Room 2105, Nanjing, China, 210017; 616.55 mg per kg of mouse body weight). 2105, Nanjing, China 210017; 616.55 mg / kg mouse body weight). 0.5% sodium carboxymethylcellulose was used as the vehicle, and test formulations were prepared daily. Dosing was performed by oral gavage using a disposable polypropylene syringe with a sterile stainless steel gavage tube. Food and water intake were monitored daily, and body weights were recorded weekly. The final dose on day 28 was administered 1 hour before the test. Sampling All animals were euthanized with 95% CO after 28 days of treatment as assigned below. Immediately after euthanasia, blood was collected via the retro-orbital route and immediately centrifuged at 1500 × g for 10 minutes at 4°C. All serum was transferred to cryogenic tubes and stored at -80°C. Forelimb grip strength test Muscle strength was assessed on days 0 and 28 by measuring forelimb grip strength using a stainless steel grill (Orchid Scientific & Innovative India Pvt Ltd, India). Grip strength was measured 1 hour after treatment. Briefly, each mouse was placed in the grill chamber, and then a steel bar was inverted. Grip strength was measured by recording the time each animal grasped the steel bar. The maximum duration of each trial was 6 minutes. Each animal underwent three independent trials separated by a 6-minute interval, and the average of the three trials was calculated. exercise training During the treatment period, motor training was performed using a motorized treadmill (Exer3 / 6, Columbus Instruments International, Ohio, USA) with a maximum running speed of 20 cm / s at a moderate intensity, a 10-degree slope, and a shock intensity of 0.2 mA for 10 minutes. The treadmill speed was manually adjusted by increasing the belt speed by 5 cm / s every 2 minutes over the total duration of 10 minutes. During the treatment period, all animals were acclimated to this procedure for 60 minutes per day, 5 days a week after administration. Treadmill endurance test On day 28 of each treatment, all animals underwent a muscular endurance test. Muscular endurance was performed using a motorized treadmill at a low to moderate maximum running speed of 5-50 cm / s, a 10° slope, and a shock intensity of 0.2 mA. The belt speed was increased by 5 cm / s every 2 min until it reached 50 cm / s. Animals continued the treadmill test until exhaustion. Distance traveled (m) was measured as a marker of motor task performance. body weight Individual body weights were recorded at admission, on the day of randomization, pre-dose on the first day of treatment (Day 1), and weekly thereafter. Weight change for all animals was calculated and reported along with the weight data. Biochemical parameters Serum and plasma samples were separated by centrifugation of blood at 8000 rpm for 10 minutes and analyzed for the following biomarkers: TC, TG, LDL and HDL, CRP, serum lactate, ammonia, glucose, NO, IL-2, IL-6, IL-10. For immune health biomarkers (T helper subsets), namely TH1, TH2, TH17, Tfh, iTreg, blood was collected into EDTA tubes. statistical analysis

[0060] Data are presented as mean ± standard deviation (SD). Statistical differences between groups were analyzed using one-way ANOVA, followed by Dunnett's test to identify significantly different pairs using GraphPad PRISM software, version 5.01 (GraphPad Software, Inc., California, USA). The level of statistical significance was set at p < 0.05. result Effects on body weight and food consumption

[0061] Significant differences were indeed observed between groups in body weight and food intake at the beginning and end. The combinations of dileucine and paraxanthine, dileucine and L-arginine, and dileucine and L-citrulline showed synergistic effects over the control group. Daily food consumption remained constant between groups over 28 days. The combination of paraxanthine and dileucine showed synergistic effects over the effects of the single substances, resulting in leaner mice over 28 days. The changes in body weight are summarized in Table 1.

[0122] [Table 1]

[0123] Effect of supplementation on forelimb grip strength

[0062] Initial and final forelimb grip strength were indeed significantly different for all groups compared to the exercise control. The combinations of dileucine and paraxanthine, dileucine and L-arginine, and dileucine and L-citrulline demonstrated synergistic effects over the control group. The combination of paraxanthine and dileucine was superior as a synergistic pairing. Changes in forelimb grip strength are summarized in Table 2.

[0124] [Table 2]

[0125] Effect of supplementation on shock frequency during treadmill exercise task

[0063] The number of shocks delivered during the initial and final treadmill exercise tasks was significantly different for all groups compared to the exercise-only control group. The combinations of dileucine and paraxanthine, dileucine and L-arginine, and dileucine and L-citrulline demonstrated synergistic effects over the control group. The combination of paraxanthine and dileucine was superior as a synergistic pairing. Changes in forelimb grip strength are summarized in Table 3.

[0126] [Table 3]

[0127]

[0064] Effect of supplementation on time spent in the shock zone during a treadmill exercise task The time spent in the shock zone during the initial and final treadmill exercise tasks was indeed different for all groups compared to the exercise-only control group. The combinations of dileucine and paraxanthine, dileucine and L-arginine, and dileucine and L-citrulline demonstrated synergistic effects over the control group. The combination of paraxanthine and dileucine was superior as a synergistic pairing. The time spent in the shock zone during the treadmill exercise tasks is summarized in Table 4.

[0128]

[0065]

[0129] [Table 4]

[0130] Effect of supplementation on distance traveled during a treadmill exercise task Distance traveled during the treadmill exercise task at the beginning and end was indeed significantly different for all groups compared to the exercise-only control group. The combinations of dileucine and paraxanthine, dileucine and L-arginine, and dileucine and L-citrulline demonstrated synergistic effects over the control group. The combination of paraxanthine and dileucine was superior as a synergistic pairing. Distance traveled during the treadmill exercise task is summarized in Table 5.

[0131] [Table 5]

[0132] Effects on blood lipids during treadmill exercise

[0067] The baseline blood lipid measurements show that the synergistic combination of paraxanthine and dileucine has an effect on total cholesterol (TC), triglycerides (TG), high-density lipids (HDL) and low-density lipids (LDL) compared to the control group after 28 days of supplementation. The blood lipid measurements are shown in Table 6.

[0133] [Table 6]

[0134] Effects of supplementation on inflammatory markers and NO signaling The synergistic combination of paraxanthine + dileucine and L-arginine + dileucine significantly increased IL-2, IL-10, and nitric oxide, and significantly decreased IL-6 and C-reactive protein (CRP) compared to the control group after 28 days of supplementation and exercise challenge. The inflammatory markers and nitric oxide measurements are shown in Table 7.

[0135] [Table 7]

[0136] Effect of supplementation on immune health biomarkers

[0069] The synergistic combination of paraxanthine and dileucine significantly increased T17 and Tfh and significantly decreased T1 and iTreg compared to the control group after 28 days of supplementation and exercise challenge. Measurements of T helper subsets, immune health biomarkers, are shown in Table 8.

[0137] [Table 8]

[0138] While multiple embodiments are disclosed, still other embodiments of the present disclosure will become apparent to those skilled in the art from the following detailed description, which shows and describes illustrative embodiments of the disclosed compositions, systems, and methods. It will be understood that the disclosed compositions, systems, and methods are capable of modification in various obvious aspects, all without departing from the spirit and scope of the present disclosure. Accordingly, the drawings and detailed description are to be regarded as illustrative in nature, and not as restrictive.

Claims

1. A composition comprising paraxanthine and dileucine or L-arginine.

2. 2. The composition of claim 1, wherein paraxanthine is present in an amount from about 2 mg to about 800 mg.

3. 3. The composition of claim 2, wherein paraxanthine is present in an amount from about 20 mg to about 600 mg.

4. 4. The composition of claim 3, wherein paraxanthine is present in an amount from about 50 mg to about 400 mg.

5. 10. The composition of claim 1, wherein the dileucine is present in an amount from about 10 mg to about 5,000 mg.

6. 6. The composition of claim 5, wherein the dileucine is present in an amount from about 25 mg to about 2,500 mg.

7. 10. The composition of claim 1, wherein the L-arginine is present in an amount of about 500 mg to about 6,000 mg.

8. 8. The composition of claim 7, wherein the L-arginine is present in an amount of about 1,000 mg to about 3,000 mg.

9. 8. The composition of claim 7, wherein the L-arginine is in the form of a free form, a salt, a bound arginine silicate complex and / or arginine alpha-ketoglutarate.

10. 1. A method for increasing muscle strength, muscle size and / or muscle function, comprising: dileucine in an amount from about 10 mg to about 5,000 mg; a) paraxanthine in an amount from about 2 mg to about 800 mg, or b) L-arginine in an amount from about 500 mg to about 6,000 mg; Administering to a subject a composition comprising:

11. 11. The method of claim 10, wherein the composition further comprises one or more compounds selected from the list consisting of isoleucine, leucine and valine, histidine, lysine, methionine, phenylalanine, threonine, tryptophan, valine, creatine, cysteine, glutamine, glycine, proline, tyrosine, carnitine, β-alanine, taurine, β-hydroxy-β-methylbutyrate, omega-3 fatty acids, vitamin D, whey protein, and other protein extracts from animal, plant, or fermentation sources.

12. 1. A method for increasing exercise performance in a subject, comprising administering to a subject a dose of about 10 mg to about 5,000 mg of dileucine; a) paraxanthine in an amount from about 2 mg to about 800 mg, or b) L-arginine in an amount from about 500 mg to about 6,000 mg; Administering to a subject a composition comprising:

13. 1. A method for promoting weight loss in a subject, comprising administering to a subject a composition comprising: dileucine in an amount from about 10 mg to about 5,000 mg; a) paraxanthine in an amount from about 2 mg to about 800 mg, or b) L-arginine in an amount from about 500 mg to about 6,000 mg; Administering to a subject a composition comprising:

14. 14. The method of claim 13, wherein the composition further comprises one or more compounds selected from the list consisting of caffeine, green tea, capsaicin, garcinia cambogia, yohimbine, and bitter orange.

15. 14. The method of claim 13, wherein weight loss is promoted through enhancing lipolysis in the subject, and wherein the composition further comprises one or more compounds selected from the list consisting of caffeine, green tea extract, L-carnitine, Garcinia cambogia (hydroxycitric acid), capsaicin, ginseng, taurine, silk peptide, catechol, epigallocatechin gallate (EGCG), catechin, proanthocyanidin, and octacosanol.

16. 1. A method of enhancing cognitive performance in a subject, comprising administering to a subject a composition comprising: dileucine in an amount from about 10 mg to about 5,000 mg; a) paraxanthine in an amount from about 2 mg to about 800 mg, or b) L-arginine in an amount from about 500 mg to about 6,000 mg; Administering a composition comprising:

17. 17. The method of claim 16, wherein the enhanced cognitive function is measured by an increase in one or more of attention, information acquisition, information processing, working memory, short-term memory, long-term memory, anterograde memory, retrograde memory, memory recall, discrimination learning, decision-making, inhibitory response control, attentional set switching ability, delayed reward reinforcement learning, reversal learning, temporal integration of spontaneous behavior, processing speed, reasoning, problem solving, and / or social cognition.

18. 1. A method of treating an inflammatory disease or condition in a subject in need thereof, comprising administering to a subject an amount of dileucine from about 10 mg to about 5,000 mg; a) paraxanthine in an amount from about 2 mg to about 800 mg, or b) L-arginine in an amount from about 500 mg to about 6,000 mg; administering to said subject a composition comprising:

19. 19. The method of claim 18, wherein the composition further comprises an additional anti-inflammatory agent, wherein the additional anti-inflammatory agent exerts an anti-inflammatory effect by inhibiting prostaglandins, increasing macrophage-mediated phagocytosis, suppressing cytokine-driven inflammation, inhibiting cytokines, inhibiting histone deacetylation, inhibiting kinases, stimulating PPARs, and / or inhibiting proteases.

20. 1. A method of enhancing joint health in a subject in need thereof, comprising: dileucine in an amount from about 10 mg to about 5,000 mg; a) paraxanthine in an amount from about 2 mg to about 800 mg, or b) L-arginine in an amount from about 500 mg to about 6,000 mg; providing to said subject a composition comprising:

21. 1. A method for enhancing immune function in a subject, comprising administering to a subject an amount of dileucine from about 10 mg to about 5,000 mg; a) paraxanthine in an amount from about 2 mg to about 800 mg, or b) L-arginine in an amount from about 500 mg to about 6,000 mg; providing to said subject a composition comprising:

22. The composition may contain cyclosporine, tacrolimus, rapamycin, omega-3 fatty acids, curcumin, S-adenosylmethionine, zinc, green tea extract, frankincense (Boswellia serrata resin), capsaicin, cat's claw (plants of the genus Uncaria including Uncaria tomentosa and Uncaria guianensis), Schizonepeta tenuifolia, pomegranate, Moringa oleifera, Ecklonia cava, limonene, sniphyllum, sulforaphane, Angelica gigas, Ascophyllum nodosum, Scutellaria baicalensis, celery seed extract, sesamin, feverfew, taurine, rosmarinic acid, Evodia rutaecarpa, green tea catechin, punicalagin, Artemisia iwayomogi, pyrroloquinoline quinone, N-acetylcysteine, king oyster mushroom, methylsulfonylmethane, α-lipoic acid, pine pollen, Sophora flavescens, Ophiopogon japonicus, Stephania tetradra, Crataegus pinnatifida, grape seed extract, bladderwrack, Paederia foetida, benfotiamine, Rubus coreanus, punicic acid, sea buckthorn, Hibiscus rosasinensis, Phellodendron amurensis, resveratrol, quercetin, rooibos, olive leaf extract, pterostilbene, Eucommia ulmoides, diindolylmethane, anatabine, serrapeptase, pelargonidin, watercress, astaxanthin, piceatannol, fish oil, glutathione, Orthosiphon stamineus, Aronia melanocarpa, blueberry, Tripterygium wilfordii, Boerhavia diffusa, whey protein, bromelain, Panax ginseng, Aloe vera, cocoa extract, nettle, garlic, Centella asiatica, Astragalus membranaceus, Dendrobium, Vitamin C, Spirulina, Berberine, Ganodermalucidum, vitamin C, vitamin D, vitamin E, lutein, leucine, dileucine, trileucine, tetraleucine, pau d'arco, AHCC, Rhodiola rosea, ashwagandha, shiitake, maitake, traiotrophoblast, monolaurin, lysine, ergothioneine, medium chain triglycerides (MCT), and butyrate.

23. 1. A method of enhancing cardiovascular health in a subject, comprising administering to a subject a composition comprising: dileucine in an amount from about 10 mg to about 5,000 mg; a) paraxanthine in an amount from about 2 mg to about 800 mg, or b) L-arginine in an amount from about 500 mg to about 6,000 mg; providing to said subject a composition comprising:

24. 1. A method of enhancing blood flow in a subject, comprising administering to a subject an amount of dileucine from about 10 mg to about 5,000 mg; a) paraxanthine in an amount from about 2 mg to about 800 mg, or b) L-arginine in an amount from about 500 mg to about 6,000 mg; providing to said subject a composition comprising:

25. 1. A method for increasing exercise endurance in a subject, comprising administering to a subject a dose of about 10 mg to about 5,000 mg of dileucine; a) paraxanthine in an amount from about 2 mg to about 800 mg, or b) L-arginine in an amount from about 500 mg to about 6,000 mg; Administering to a subject an effective amount of a composition comprising:

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