Compositions using a combination of curcumin and omega-3 fatty acids for cellular energy

Abstract

The composition can be used for various therapeutic purposes, including treating and / or preventing diseases or disorders associated with reduced or insufficient mitochondrial activity, such as aging or stress, diabetes, obesity, and neurodegenerative diseases. The composition can be administered to middle-aged or elderly individuals. It can also be administered to patients in ICUs. The composition contains a combination of curcumin and omega-3 fatty acids. The composition can be a food product, a dietary supplement, or a nutraceutical. The composition can also be advantageously used in generally healthy individuals to increase or maintain metabolic rate, reduce body fat percentage, increase or maintain muscle mass, manage weight, improve or maintain mental performance (including memory), improve or maintain muscle performance, improve or maintain mood, and manage stress.

Description

[Background Art]

[0001]

[0001] The present disclosure generally relates to compositions and methods capable of treating or preventing mitochondrial-related diseases, or conditions associated with altered mitochondrial function, or reduced mitochondrial density, for example by improving antioxidant capacity, reducing oxidative stress, and / or improving mitochondrial function, in some embodiments in middle-aged or elderly subjects.

[0002]

[0002] Population aging is a remarkable demographic event. As the increase in the elderly population outpaces the growth of the total population due to extended life expectancy, the proportion of the elderly population relative to the rest of the population has increased significantly, also driven by declining birth rates. For example, while one in twelve people was an elderly individual aged 60 years or older in the 1950s, by the end of the 2000s, one in ten people was an elderly individual aged 60 years or older. It is projected that by the end of the 2050s, one in five people globally will be an elderly individual aged 60 years or older.

[0003]

[0003] In middle-aged and older adults, some degree of cognitive impairment, including age-related cognitive decline, is common, and age-related changes in brain morphology and cerebrovascular function are generally observed. Cognitive decline has been reported in conjunction with aging in a wide range of cognitive areas, including processing speed, attention, episodic memory, spatial ability, and executive function. Brain imaging studies have shown that these typical age-related cognitive declines are associated with a decrease in the volume of both gray and white matter in the brain, with the striatum frontalis system being the most severely damaged with age. Such a decrease in cortical volume may be due to many harmful cellular processes involved in normal aging, such as the accumulation of long-term damage from free radicals that cause oxidative damage, chronic mild inflammation, homocysteine ​​accumulation (which, when increased, is a risk factor for cognitive impairment and dementia), and decreased mitochondrial function. In addition to direct cellular damage, the brain also suffers indirect damage from damage to the microvascular structure. It is clear that the pathology of aging, and even dementia, involves complex interactions between these interrelated factors. For example, mitochondrial dysfunction can result in increased oxidative stress, which can trigger inflammation and vascular damage.

[0004]

[0004] Furthermore, cognitive decline is an early predictor of Alzheimer's disease and begins before the onset of dementia. In this case, a comprehensive score for cognitive function is a reliable means of assessing cognitive decline that occurs before dementia. Much evidence suggests that maintaining brain health and preventing age-related cognitive decline can prevent or slow the progression of Alzheimer's disease and other age-related neuropathological dementias.

[0005]

[0005] In recent years, nutrition, education, exercise, and cognitive exercise have been demonstrated as interventions that can prevent age-related cognitive decline. Abundant clinical, epidemiological, and individualized evidence supports that individual nutritional factors reduce the risk of dementia and age-related neurodegeneration. However, the results obtained from formal trials of nutritional interventions have been mixed (Schmitt et al., Nutrition Reviews 68:S2-S5 (2010)).

[0006]

[0006] Furthermore, stress (generally, an animal's response to a change that requires physical, mental, or emotional regulation or response) can cause health problems in animals. Prolonged, uninterrupted, unexpected, and uncontrollable stress is the most harmful of all types of stress.

[0007]

[0007] There are known methods to act on stress and the symptoms and conditions caused by stress. Medications that suppress depression, for example, can be used to act on stress and the symptoms and conditions associated with it. Antidepressants such as Prozac®, Deroxat®, and Zoloft®, or anxiolytics such as Xanax®, Temesta®, Lexomil®, and Valium®, are prescribed to treat stress and act on the symptoms and conditions caused by stress. However, these methods often come with one or more side effects. Meditation, relaxation, hypnosis, exercise, counseling, and nutrition are known methods to act on stress and the symptoms and conditions caused by stress.

[0008]

[0008] Furthermore, the psychobiological characteristics of stress may manifest as oxidative stress, that is, as a state in which the balance between the production and expression of reactive oxygen species and the ability of the biological system to rapidly detoxify reactive intermediates or rapidly repair the resulting damage is disrupted. When the normal redox state of tissue is disrupted, toxic effects can be triggered by the production of peroxides and free radicals that damage all components of cells, such as proteins, lipids, and DNA. Some reactive oxidative species can also act as messengers through a phenomenon called "redox signaling."

[0009]

[0009] In humans, oxidative stress is involved in many diseases. Examples include atherosclerosis, Parkinson's disease, heart failure, myocardial infarction, Alzheimer's disease, schizophrenia, bipolar disorder, fragile X syndrome, and chronic fatigue syndrome.

[0010]

[0010] One of the sources of reactive oxygen species under normal conditions in humans is the leakage of reactive oxygen species from mitochondria during oxidative phosphorylation. Other enzymes that can produce superoxide (O2-) include xanthine oxidase, NADPH oxidase, and cytochrome P450. Another potent oxidizing agent, hydrogen peroxide, is produced by a variety of enzymes, including several oxidases. Reactive oxygen species play an important role in cellular signaling processes called redox-dependent signaling. Therefore, a balance between the production and consumption of reactive oxygen species is necessary to maintain proper cellular homeostasis. [Overview of the project]

[0011]

[0011] In consideration of the experimental data to be disclosed later herein, the inventors believe that curcumin and omega-3 fatty acids synergistically improve the energy production efficiency of mitochondria.

[0012] Therefore, in general embodiments, the present disclosure provides a method for improving antioxidant capacity, reducing oxidative stress, and / or improving mitochondrial function, the method comprising administering an effective amount of curcumin and an omega-3 fatty acid combination to an individual requiring administration.

[0013] In another embodiment, the disclosure provides a method for treating, reducing the incidence of, and / or reducing the severity of mitochondrial-related diseases, conditions associated with altered mitochondrial function, or decreased mitochondrial density, the method comprising orally administering an effective amount of curcumin and an omega-3 fatty acid combination to an individual in need of administration.

[0014] In a further embodiment, a method is provided for healthy middle-aged and elderly individuals to delay the onset of metabolic decline, maintain muscle mass, reduce oxidative stress, maintain immune function, and / or maintain cognitive function, the method comprising orally administering an effective amount of curcumin and omega-3 fatty acids to the healthy middle-aged and elderly individuals.

[0015] Furthermore, the present invention relates to a method for enhancing the metabolism of reactive oxygen species, improving glucose regulation, and / or improving muscle function in individuals having at least one of obesity or diabetes, the method comprising orally administering to the individual an effective amount of a combination of curcumin and omega-3 fatty acids.

[0016] In another embodiment, this disclosure, i) A method for improving mitochondrial function in an individual, comprising orally administering to the individual an effective amount of a combination of curcumin and omega-3 fatty acids, ii) A method for increasing metabolic rate, comprising orally administering to an individual an effective amount of a combination of curcumin and omega-3 fatty acids, iii) A method for improving or maintaining cognitive function, comprising orally administering to an individual an effective amount of a combination of curcumin and omega-3 fatty acids. iv) A method for enhancing at least one of mental performance or muscular performance, comprising orally administering to an individual an effective amount of a combination of curcumin and omega-3 fatty acids, v) The method according to claim 22, wherein the individual is a middle-aged or elderly person, an elderly person, or an ICU patient. vi) A method for weight management comprising orally administering to an individual an effective amount of a combination of curcumin and omega-3 fatty acids. vii) A method for improving or maintaining mitochondrial function, comprising administering to an individual an effective amount of a combination of curcumin and omega-3 fatty acids, To provide.

[0017] In further embodiments, the present disclosure relates to compositions in unit dosage forms comprising a combination of curcumin and an omega-3 fatty acid in an amount effective for at least one of the following: (i) treating, reducing the incidence, or reducing the severity of mitochondrial-related diseases or conditions associated with altered mitochondrial function or decreased mitochondrial density; (ii) increasing metabolic rate; (iii) improving or maintaining cognitive function; (iv) enhancing mental performance; (v) enhancing muscular performance; (vi) managing body weight; or (vii) improving or maintaining mitochondrial function.

[0018] In another embodiment, the disclosure provides a kit containing curcumin and omega-3 fatty acids in one or more containers.

[0019]

[0012] The advantage of one or more embodiments provided by this disclosure is that they promote healthy aging of cells.

[0020]

[0013] Another advantage of one or more embodiments provided by this disclosure is that they help to counteract the slowing of metabolism associated with aging.

[0021]

[0014] Another advantage of one or more embodiments provided by this disclosure is that they help increase fatty acid metabolism.

[0022]

[0015] Yet another advantage of one or more embodiments provided by the present disclosure is that it assists the body in metabolizing fat and increasing lean body mass.

[0023]

[0016] An advantage of one or more embodiments provided by the present disclosure is that it assists in maintaining heart health.

[0024]

[0017] Another advantage of one or more embodiments provided by the present disclosure is that it assists in maintaining healthy LDL cholesterol concentrations and fatty acid concentrations in blood.

[0025]

[0018] Another advantage of one or more embodiments provided by the present disclosure is that it assists in maintaining healthy muscle mass.

[0026]

[0019] Yet another advantage of one or more embodiments provided by the present disclosure is that it assists in reducing oxidative stress to the body.

[0027]

[0020] Additional features and advantages are described herein, and will be apparent from the following drawings and the detailed description of the invention. Brief Description of the Drawings

[0028]

[0021] Figures 1 to 3 are graphs plotting data of the experimental examples disclosed in the present specification. [Figure 1] It is a diagram showing the effects of curcumin (CUR), n-3 fatty acids (OM3), and a combination of curcumin and n-3 FA (CUR+OM3) on mitochondrial complex activity in aged rats. 20-month-old rats were fed either a control diet or a diet supplemented with curcumin and optionally n-3 FA for one month. The results are expressed as mean ± standard error. [Figure 2]This figure shows the effects of curcumin (CUR), n-3 fatty acids (OM3), and a combination of curcumin and n-3 FA (CUR+OM3) on citrate synthase activity in aged rats. 20-month-old rats were fed either a control diet or a diet supplemented with curcumin and optionally n-3 FA for one month. Results are expressed as mean ± standard error. [Figure 3] This study investigated the effects of curcumin (CUR), n-3 fatty acids (OM3), and a combination of curcumin and n-3 FA (CUR+OM3) on the MFN2 / DRP1 protein level ratio in aged rats. 20-month-old rats were fed either a control diet or a diet supplemented with curcumin and optionally n-3 FA for one month. Results are expressed as mean ± standard error. [Modes for carrying out the invention]

[0029]

[0025] Definition

[0026] The following are some definitions. However, definitions may also be found in the "Embodiments" section below, and the above heading "Definitions" does not mean that such disclosures in the "Embodiments" section are not definitions.

[0030]

[0027] All percentages described herein are by total weight of the composition unless otherwise stated. When used herein, “about,” “approximately,” and “substantially” are understood to refer to numbers within a numerical range, for example, within -10% to +10% of the reference digit, preferably within -5% to +5%, more preferably within -1% to +1% of the reference digit, and most preferably within -0.1% to +0.1% of the reference digit. All numerical ranges herein should be understood to include all integers or fractions within that range. Furthermore, these numerical ranges should be interpreted as supporting claims that cover any number or subset of a number within that range. For example, a disclosure of 1 to 10 should be interpreted as supporting ranges such as 1 to 8, 3 to 7, 1 to 9, 3.6 to 4.6, 3.5 to 9.9, etc.

[0031]

[0028] When used in the present disclosure and the appended claims, the singular forms “one,” i.e., “a,” “an,” and “the,” also include multiple references unless otherwise indicated. Thus, for example, a reference to “a component” or “the component” includes two or more components.

[0032]

[0029] The terms “comprise,” “comprises,” and “comprising” should be interpreted inclusively, not exclusively. Similarly, the terms “include,” “including,” and “or” should all be interpreted inclusively unless such interpretation is clearly prevented by the context. However, compositions disclosed herein may not include elements not specifically disclosed herein. Accordingly, disclosures of embodiments using the term “comprising” include disclosures of embodiments that “consist essentially of” and embodiments that “consist of” the specified components. A composition that “consist essentially of” means that contains at least 50% by weight of the referenced component, preferably at least 75% by weight of the referenced component, more preferably at least 85% by weight of the referenced component, and most preferably at least 95% by weight of the referenced component.

[0033]

[0030] The term "and / or" used in the context of "X and / or Y" should be interpreted as "X" or "Y" or "X and Y". Similarly, "at least one of X or Y" should be interpreted as "X" or "Y" or "X and Y". For example, "at least one of mental performance or muscular performance" should be interpreted as "mental performance or muscular performance" or "muscular performance" or "both mental performance and muscular performance".

[0034]

[0031] When used herein, the terms “example” and “for example, etc.” are merely illustrative and descriptive, and should not be considered exclusive or exhaustive, especially when followed by a list of terms. When used herein, a state “related to” or “associated with” another state means that these states occur simultaneously, preferably that they are caused by the same underlying state, and most preferably that one of the specified states is caused by the other specified state.

[0035]

[0032] The terms “food,” “food product,” and “food composition” mean a product or composition intended for consumption by an individual, such as a human, and providing to such individual at least one nutrient. Food products typically contain at least one of proteins, lipids, and carbohydrates, and optionally one or more vitamins and minerals. The compositions of this disclosure, including many embodiments described herein, may consist of, or be essentially composed of, the elements disclosed herein, as well as any additional or optionally present components, components, or elements described or not described herein that are useful in a diet.

[0036]

[0033] As used herein, the term “isolated” means that a compound has been removed from one or more other compounds or components that, if not isolated, might be found together with that compound, for example, in nature. Preferably, for example, “isolated” means that the identified compound has been separated from at least a portion of cellular material that is typically found together with it in nature. In one embodiment, the isolated compound is pure, i.e., free from other compounds.

[0037]

[0034] As used herein, “effective amount” means an amount that prevents a deficiency, treats a disease or medical condition in an individual, or more generally, alleviates symptoms, manages the progression of a disease, or provides a nutritional, physiological or medical benefit to the individual. Relative terms such as “improved,” “increased,” and “enhanced” indicate the effect of the compositions disclosed herein, i.e., compositions containing a combination of curcumin and omega-3 fatty acids, compared to a composition that is otherwise identical but does not contain curcumin and omega-3 fatty acids. As used herein, “enhancing” means enhancing or inducing compared to the level of the composition disclosed herein before administration.

[0038]

[0035] The term “unit dosage form” as used herein refers to a physically distinct unit suitable as a unit dose for human and animal subjects, each unit containing a specified amount of the composition disclosed herein in an amount sufficient to produce the desired effect, preferably together with a pharmaceutically acceptable diluent, carrier, or vehicle. The specifications of a unit dosage form depend on the specific compound used, the effect to be achieved, and the pharmacodynamics relating to each compound in the host body. In some embodiments, a unit dosage form may be a specified amount of the active compound in a single serving of food product, a specified amount of the powder in a sachet, a specified amount of the active compound in a capsule or tablet, or a specified amount of the active compound in a specified amount of liquid, preferably a therapeutic or prophylactic dose, or a specified portion of a therapeutic or prophylactic dose.

[0039]

[0036] The "subject" or "individual" is a mammal, preferably a human. In the context of humans, the term "elderly" means a postnatal age of 60 years or older, preferably 63 years or older, more preferably 65 years or older, and most preferably 70 years or older. In the context of humans, the term "older adult" means a postnatal age of 45 years or older, preferably 50 years or older, more preferably 55 years or older, and includes elderly people.

[0040]

[0037] As used herein, “frailty” is defined as a clinically recognizable condition in which increased vulnerability results from a decline in reserve capacity and function across multiple physiological systems with age, impairing the ability to cope with everyday or acute stressors. Pre-frailty stages that have one or two of these criteria are identified as being at high risk of progressing to frailty.

[0041]

[0038] "Overweight" in humans refers to a body mass index (BMI) of 25-30 kg / m². 2 It is defined as having a BMI of at least 30 kg / m². "Obesity" in humans is defined as having a BMI of at least 30 kg / m². 2 For example, 30-39.9 kg / m 2 Weight loss is defined as a decrease in total body weight. Weight loss can refer to a decrease in total body weight for the purpose of improving one or more of the following: health, fitness, or appearance.

[0042]

[0039] "Diabetes mellitus" encompasses both type I and type II of this disease. Non-limiting examples of risk factors for diabetes mellitus include a waist circumference of more than 40 inches for men or more than 35 inches for women, a blood pressure of 130 / 85 mmHg or higher, triglycerides greater than 150 mg / dL, fasting blood glucose greater than 100 mg / dL, or high-density lipoprotein levels of less than 40 mg / dL for men or less than 50 mg / dL for women.

[0043]

[0040] As used herein, the term “metabolic syndrome” refers to a combination of medical abnormalities that, when occurring together, increase the risk of developing cardiovascular disease and diabetes. One in five people in the United States have metabolic syndrome, and the prevalence increases with age. Some studies estimate the prevalence in the United States to be 25% of the population. According to the International Diabetes Foundation’s consensus worldwide definition (2006), metabolic syndrome is central obesity plus any two of the following:

[0041] Elevated triglycerides: greater than 150 mg / dL (1.7 mmol / L), or treatment targeting this lipid abnormality;

[0042] Decrease in HDL cholesterol: less than 40 mg / dL (1.03 mmol / L) in men, less than 50 mg / dL (1.29 mmol / L) in women, or treatment targeting this dyslipidemia;

[0043] Elevated blood pressure: systolic BP greater than 130 or diastolic BP greater than 85 mmHg, or treatment of previously diagnosed hypertension; and

[0044] Elevated fasting plasma glucose (FPG) level greater than 100 mg / dL (5.6 mmol / L), or a previous diagnosis of type 2 diabetes.

[0044]

[0045] As used herein, “neurodegenerative disease” or “neurodegenerative disorder” refers to any condition in which functional neurons in the central nervous system gradually decrease. In one embodiment, neurodegenerative disease is associated with age-related cell death. Non-exclusive examples of neurodegenerative diseases include Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis (also known as ALS and Lou Gehrig’s disease), AIDS dementia, adrenoleukodystrophy, Alexander disease, Alpers disease, ataxia telangiectasia, Batten disease, bovine spongiform encephalopathy (BSE), Canavan disease, corticobasal degeneration, Creutzfeldt-Jakob disease, Lewy body dementia, fatal familial insomnia, and others. Examples include craniotemporal lobar degeneration, Kennedy disease, Krabbe disease, Lyme disease, Machado-Joseph disease, multiple sclerosis, multiple system atrophy, neuroacanthocytosis, Niemann-Pick disease, Pick disease, primary lateral sclerosis, progressive supranuclear palsy, Refsum disease, Sandhoff disease, diffuse myelin-destructive sclerosis, spinocerebellar ataxia, subacute combined degeneration of the spinal cord, tabes dorsalis, Tay-Sachs disease, toxic encephalopathy, infectious spongiform encephalopathy, and hedgehog wobbly syndrome.

[0045] As used herein, “cognitive function” means any mental process that involves symbolic activity, such as perception, memory, attention, speech comprehension, speech production, reading comprehension, image creation, learning, and reasoning, preferably with at least memory.

[0046]

[0046] Methods for measuring cognitive function are well known and may include, for example, individual or battery tests on any feature of cognitive function. One such test is the Prudhoe Cognitive Function Test by Margallo-Lana et al. (2003) J. Intellect. Disability Res. 47:488-492. Another such test is the Mini Mental State Exam (MMSE), which is designed to assess orientation to time and place, memory, attention and calculation, recall, language use and comprehension, repetition, and complex commands. As used herein, “cognitive impairment” refers to any condition that reduces cognitive function. Non-limiting examples of cognitive impairment include delirium, dementia, learning disabilities, attention deficit disorder (ADD), and attention deficit hyperactivity disorder (ADHD). “Stress-induced or stressor-related cognitive impairment” refers to a disturbance in cognitive function that is induced by or associated with stress.

[0047]

[0047] As used herein, “mood disorder” (also known as affective disorder) refers to a disturbance of the emotional state as described in the Diagnostic and Statistical Manual of Mental Disorders published by the American Psychiatric Association. Non-exclusive examples of mood disorders include major depression, postpartum depression, dysthymia, and bipolar disorder. “Stress-induced or stressor-related mood disorder” refers to a disturbance of the emotional state that is triggered by or associated with stress. Such mood disorders are sometimes called reactive mood disorders and are distinguished from other mood disorders, such as “organic” mood disorders, which are caused by a medical or health condition rather than a mental illness.

[0048]

[0048] As used herein, “anxiety disorder” refers to a dysfunction of fear and anxiety, for example, fear and anxiety that are not proportional to a stressful situation or prediction of a stressful situation. Non-exclusive examples of anxiety disorders include generalized anxiety disorder, panic disorder, panic disorder with agoraphobia, agoraphobia, social anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress disorder. “Stress-induced anxiety disorder or stressor-related anxiety disorder” refers to a dysfunction of fear and anxiety that is triggered by or associated with stress. Such anxiety disorders are sometimes called reactive anxiety disorders and are distinguished from other anxiety disorders, such as “organic” anxiety disorders, which are caused by a medical or health condition rather than a mental illness.

[0049]

[0049] Embodiment

[0001] The present disclosure provides compositions comprising a combination of curcumin and an omega-3 fatty acid. In preferred embodiments, the fatty acid comprises an essential polyunsaturated fatty acid, namely linoleic acid (C18:2n-3) or alpha-linoleic acid (C18:3n-3), or a long-chain polyunsaturated fatty acid, such as eicosapentaenoic acid (C20:5n-3), docosahexaenoic acid (C22:6n-3), or any combination thereof. More preferably, the omega-3 fatty acid is eicosapentaenoic acid.

[0050]

[0002] Curcumin may be present in an amount of about 0.01 mg to about 2.0 g per serving, preferably about 0.1 mg to about 2.0 g per serving, and more preferably about 10.0 mg to about 1.0 g per serving.

[0051]

[0003] Omega-3 fatty acids may be at least about 10% by weight, preferably at least about 15% by weight, based on the total lipid content. In a preferred embodiment, the daily amount of omega-3 fatty acids is about 500 mg to about 5 g of omega-3 fatty acids per day, preferably 500 mg to 2.5 g of omega-3 fatty acids per day, and more preferably about 1.5 g to about 2 g of omega-3 fatty acids per day. The omega-3 fatty acids preferably include eicosapentaenoic acid.

[0052]

[0050] Some embodiments of the compositions disclosed herein may include a plant extract that provides at least a portion of curcumin, for example, an extract of Curcuma longa (e.g., its root). The plant extract may be rich in curcumin, for example, containing at least about 10% by weight of curcumin, preferably at least about 20% by weight of curcumin, more preferably at least about 30% by weight of curcumin, and most preferably at least about 50% by weight of curcumin. Additionally or alternatively, the portion of curcumin may be isolated curcumin.

[0053]

[0051] In some embodiments of the compositions disclosed herein, at least a portion of the curcumin is highly bioavailable curcumin. Curcumin has poor absorption, distribution in the body, metabolism, and bioavailability. As a result of continued research on curcumin, several possibilities for overcoming these problems have been identified. Various formulations, including nanoparticles, liposomes, micelles, and phospholipid complexes, have been developed to improve the bioavailability, longer circulation, better permeability, and resistance to metabolic processes of curcumin.

[0054]

[0052] In addition to curcumin, the composition may contain one or more additional polyphenols, such as flavonoids, such as isoflavones, anthocyanins, proanthocyanidins and anthocyanidins, flavans, flavonols, flavones and flavanones. Specific examples of bioflavonoids include catechins (catechin, epicatechin, gallocatechin, epigallocatechin, epicatechin gallate, epigallocatechin gallate), oleuropein, hesperidin, and genistein.

[0055]

[0053] Another anti-inflammatory compound or antioxidant may optionally be used in the composition. For example, additional antioxidants may be provided as an antioxidant-rich food composition or as an extract thereof. An antioxidant-rich food composition has an ORAC (Oxygen Radical Absorption Capacity) score of at least 100 per 100g of the composition.

[0056]

[0054] While not bound by theory, it is thought that various types of stress can lead to mitochondrial stress damage, reducing the ability of mitochondria to perform numerous roles essential to overall cellular function. The methods disclosed herein may be useful in treating conditions involving mitochondrial stress damage. This damage can manifest through any of many pathways, including but not limited to mitochondrial diseases.

[0057]

[0055] Mitochondrial diseases result from either genetic mutations or spontaneous mutations in mitochondrial DNA or nuclear DNA, causing alterations in the function of proteins or RNA molecules normally present in mitochondria. However, problems with mitochondrial function can affect only specific tissues due to developmental and growth-related factors that are not yet fully understood. Even considering tissue-specific isoforms of mitochondrial proteins, it is difficult to explain the variable patterns of organ systems affected by mitochondrial disease syndromes observed clinically.

[0058]

[0056] Mitochondrial diseases are caused by damage to mitochondria, which are special compartments present in all cells of the body except red blood cells. Mitochondria are involved in the production of more than 90% of the energy that the body needs to maintain life and support development. When mitochondria stop functioning, the amount of energy produced in cells decreases. Cells become damaged and eventually die. If this process is repeated throughout the body, the entire system begins to break down, and this breakdown severely threatens the person's life. Mitochondrial diseases mainly affect children, but cases in adults are also being observed.

[0059]

[0057] Mitochondrial diseases appear to primarily damage cells in the brain, heart, liver, skeletal muscle, kidneys (e.g., renal failure), as well as the endocrine and respiratory systems.

[0060]

[0058] Many symptoms in mitochondrial disease are nonspecific. Symptoms may also present as a transient course with periodic exacerbations. Review articles in mitochondrial medicine have mentioned transient migraine episodes, as well as muscle pain, gastrointestinal symptoms, tinnitus, depression, chronic fatigue, and diabetes, among the various manifestations of mitochondrial disease. In patients with mitochondrial disease, clinical symptoms typically occur when energy demands are high, associated with the illness, hunger, excessive exercise, and extreme environmental temperatures. Furthermore, psychological stressors often trigger symptoms, perhaps due to excessive brain energy demands that prevent the patient from producing enough ATP.

[0061]

[0059] Depending on which cells are affected, symptoms may include decreased motor function, muscle weakness and pain, gastrointestinal disorders and swallowing difficulties, growth retardation, heart disease, liver disease, diabetes, respiratory complications, seizures, visual / hearing impairment (e.g., decreased vision or hearing loss), lactic acidosis, developmental delay, and increased susceptibility to infection.

[0062]

[0060] Mitochondrial diseases include, but are not limited to, Alper's disease, Barth syndrome, β-oxidation disorders, carnitine deficiency, carnitine-acyl-carnitine deficiency, chronic progressive extraophthalmoplegia syndrome, coenzyme Q10 deficiency, complex I deficiency, complex II deficiency, complex III deficiency, complex IV deficiency, complex V deficiency, CPT I deficiency, CPT II deficiency, creatine deficiency syndrome, cytochrome c oxidase deficiency, glutaricemia type 2, Kearns-Sayre syndrome, lactic acidosis, LCHAD (long-chain acyl-CoA dehydrogenase deficiency), Leigh hereditary optic neuropathy, Leigh disease, and lethal infantile cardiomyopathy. Examples include cardiomyopathy, Luft's disease, MAD (medium-chain acyl-CoA dehydrogenase deficiency), mitochondrial cell dystrophy, mitochondrial DNA depletion, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like symptoms, mitochondrial encephalopathy, mitochondrial myopathy, mitochondrial recessive ataxia syndrome, muscular dystrophy, myoclonic epilepsy, and ragged-red fiber disease, myoneurogenic gastrointestinal encephalopathy, neuropathy, ataxia, retinitis pigmentosa, and ptosis, Pearson syndrome, POLG mutation, pyruvate carboxylase deficiency, pyruvate dehydrogenase deficiency, SCHAD (short-chain acyl-CoA dehydrogenase deficiency), and very long-chain acyl-CoA dehydrogenase deficiency.

[0063]

[0061] Accordingly, one aspect of the present disclosure is a composition in a unit dosage form comprising a combination of curcumin and an omega-3 fatty acid in an amount effective for the treatment or prevention of at least one symptom selected from the group consisting of stress (e.g., childhood stress and / or its effects), obesity, decreased metabolic rate, metabolic syndrome, diabetes mellitus, hyperlipidemia, neurodegenerative diseases, cognitive impairment, stress-induced or stressor-related cognitive dysfunction, mood disorders (e.g., stress-induced or stressor-related mood disorders), anxiety disorders (e.g., stress-induced or stressor-related anxiety disorders), and age-related neuronal death or dysfunction (e.g., age-related neuronal death or dysfunction not attributable to a specific neurodegenerative disease), trauma, infection (e.g., ICU), or cancer.

[0064]

[0062] Another aspect of the present disclosure is a method for treating in an individual having at least one of the following conditions, selected from the group consisting of stress (e.g., childhood stress and / or its effects), obesity, decreased metabolic rate, metabolic syndrome, diabetes mellitus, cardiovascular disease, hyperlipidemia, neurodegenerative disease, cognitive impairment, stress-induced or stressor-related cognitive dysfunction, mood disorders (e.g., stress-induced or stressor-related mood disorders), anxiety disorders (e.g., stress-induced or stressor-related anxiety disorders), and age-related neuronal death or dysfunction (e.g., age-related neuronal death or dysfunction not attributable to a specific neurodegenerative disease), trauma, infection (e.g., ICU), or cancer. The method comprises administering to the individual a composition comprising a therapeutically effective amount of curcumin and an omega-3 fatty acid combination.

[0065]

[0063] Further aspects of the present disclosure are methods for preventing at least one condition selected from the group consisting of stress, obesity, decreased metabolic rate, metabolic syndrome, diabetes mellitus, cardiovascular disease, hyperlipidemia, neurodegenerative disease, cognitive impairment, stress-induced or stressor-related cognitive dysfunction, mood disorders (e.g., stress-induced or stressor-related mood disorders), anxiety disorders (e.g., stress-induced or stressor-related anxiety disorders), and age-related neuronal death or dysfunction (e.g., age-related neuronal death or dysfunction not attributable to a specific neurodegenerative disease), trauma, infection (e.g., in an ICU), or cancer. The method comprises administering to an individual at risk of at least one condition a composition comprising a combination of curcumin and an omega-3 fatty acid in a prophylactically effective amount.

[0066]

[0064] In one embodiment of these methods, the hyperlipidemia to be treated or prevented includes hypertriglyceridemia. In one embodiment of these methods, the hyperlipidemia to be treated or prevented includes an increase in free fatty acids. In one embodiment of these methods, age-related neuronal cell death or dysfunction to be treated or prevented is by administering the composition to middle-aged or elderly persons, such as the elderly.

[0067]

[0065] The stress to be treated or prevented may be early childhood stress, i.e., stress experienced during the period up to 5 years of age. Early childhood stress has been reported to have a significant adverse effect on cognitive abilities, including psychological parameters such as an increased incidence of or susceptibility to depression, anxiety, and abnormal risk-taking behaviors. Individuals who have experienced early childhood stress have been reported to have a higher incidence of attention deficit / hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD), and major depressive disorder.

[0068]

[0066] Another aspect of the present disclosure is a method for delaying the onset of metabolic decline, maintaining muscle mass, reducing oxidative stress, maintaining immune function, and / or maintaining cognitive function in healthy middle-aged and elderly individuals. The method comprises administering an effective amount of curcumin in combination with an omega-3 fatty acid to healthy middle-aged and elderly individuals.

[0069]

[0067] Another aspect of the present disclosure is a method for improving mitochondrial function in individuals such as middle-aged or elderly persons. This method comprises administering to an individual an effective amount of a combination of curcumin and omega-3 fatty acids.

[0070]

[0068] A further aspect of the present disclosure is a method for enhancing the metabolism of reactive oxygen species, improving glucose regulation, and / or improving muscle function in an individual having at least one of obesity or diabetes. The method comprises administering to the individual an effective amount of a combination of curcumin and omega-3 fatty acids.

[0071]

[0069] Another aspect of the present disclosure is a method for improving mitochondrial function (preferably benefiting at least one of metabolism or muscle strength) in individuals such as middle-aged or elderly persons. The method comprises administering to the individual an effective amount of a combination of curcumin and omega-3 fatty acids.

[0072]

[0070] Another aspect of the present disclosure is a composition comprising curcumin and optionally omega-3 fatty acids in amounts effective for weight management. For adults (e.g., at least 18 years post-birth), “weight management” means that the individual has approximately the same body mass index (BMI) after taking the composition for one week, preferably after taking the composition for one month, and more preferably after taking the composition for one year, compared to the BMI at the start of taking the composition. For young individuals, “weight management” means that the BMI percentile for individuals of the corresponding age is approximately the same after taking the composition for one week, preferably after taking the composition for one month, and more preferably after taking the composition for one year, compared to the BMI percentile at the start of taking the composition. In some embodiments, the individual receiving weight management is an overweight individual whose obesity is being prevented.

[0073]

[0071] In related embodiments, a method for managing the weight of an individual includes administering to the individual a composition comprising an effective amount of curcumin and a combination of omega-3 fatty acids.

[0074]

[0072] Another aspect of the present disclosure is a composition in a unit dosage form comprising a combination of curcumin and an omega-3 fatty acid in an amount effective in improving at least one of muscle performance or mental performance (e.g., memory). In a relevant embodiment, a method for improving at least one of muscle performance or mental performance (e.g., memory) in an individual comprises administering to the individual a composition comprising a combination of curcumin and an omega-3 fatty acid in an effective amount.

[0075]

[0073] With respect to muscle performance, improvement in muscle performance may be one or more of the following: improvement in muscle function, reduction of decline in muscle function, improvement in muscle strength, improvement in muscle endurance, and improvement in muscle recovery. The composition can improve physical endurance (e.g., the ability to perform physical work such as exercise, manual labor, and sports activities), suppress or delay physical fatigue, improve blood oxygen levels, improve energy in healthy individuals, improve work capacity and endurance, reduce muscle fatigue, reduce stress, enhance the function of cardiomyocytes, improve sexual performance, increase muscle ATP levels, and / or reduce lactic acid in the blood. "Endurance" refers to the time until fatigue occurs when exercising at a constant workload, generally at an intensity of less than 80% of V02max. In some embodiments, the composition is administered in amounts that increase mitochondrial activity, increase mitochondrial biogenesis, and / or increase mitochondrial mass. In some embodiments, the composition is administered in combination with exercise and / or exercise therapy to improve muscle performance and / or muscle endurance.

[0076]

[0074] In some embodiments, the combination of curcumin and omega-3 fatty acids is administered to individuals with reduced physical capacity, reduced endurance, and / or reduced muscle function. Improved muscle function may be particularly effective in elderly subjects whose muscle cell function is reduced as a result of age-related conditions. For example, subjects who may experience reduced muscle function that could later lead to pre-frailty and frailty may benefit from improved muscle cell function. Such subjects do not necessarily experience muscle wasting along with reduced muscle function. Some subjects experience both muscle wasting and reduced muscle function. The combination of curcumin and omega-3 fatty acids can enhance muscle performance in subjects that are frail or pre-frail.

[0077]

[0075] Sports performance refers to the ability of an athlete's muscles to perform when participating in sports activities. Improvements in sports performance, strength, speed, and endurance are measured by increasing the intensity of muscle contraction, increasing the amplitude of muscle contraction, or shortening the muscle reaction time between stimulus and contraction. An "athlete" refers to an individual who participates in any level of sport, such as a bodybuilder, cyclist, long-distance runner, or sprinter, and aims to improve strength, speed, or endurance in their performance. Improvements in sports performance manifest as the ability to overcome muscle fatigue, the ability to sustain activity for longer periods, and the ability to perform more effective workouts.

[0078]

[0076] The compositions and methods disclosed herein may also be effective in treating neuromuscular diseases such as myopathy and Duchenne muscular dystrophy, and / or pathological conditions related to muscles, including cachexia associated with burns, bed rest, limb immobilization, or major surgery of the chest, abdomen, and / or orthopedics.

[0079]

[0077] Further embodiments of the present disclosure include compositions comprising a combination of curcumin and an omega-3 fatty acid in an amount effective for improving or maintaining at least one of mitochondrial function or metabolic rate. In relevant embodiments, a method for improving or maintaining at least one of mitochondrial function or metabolic rate in an individual comprises administering to the individual a composition comprising an effective amount of a combination of curcumin and an omega-3 fatty acid.

[0080]

[0078] A further aspect of the present disclosure is a composition in a unit dosage form comprising a combination of curcumin and an omega-3 fatty acid in an amount effective for treating, preventing or managing at least one of mitochondrial-related diseases, conditions associated with altered mitochondrial function, or decreased mitochondrial density. In a related embodiment, a method for treating an individual having at least one of mitochondrial-related diseases, conditions associated with altered mitochondrial function, or decreased mitochondrial density comprises administering to the individual a composition comprising an effective amount of a combination of curcumin and an omega-3 fatty acid. In another related embodiment, a method for preventing at least one of mitochondrial-related diseases, conditions associated with altered mitochondrial function, or decreased mitochondrial density in an individual at risk thereof comprises administering to the individual a composition comprising an effective amount of a combination of curcumin and an omega-3 fatty acid.

[0081]

[0079] Another aspect of the present disclosure is a composition in a unit dosage form comprising a combination of curcumin and an omega-3 fatty acid in an amount effective for improving or maintaining cognitive function. In a relevant embodiment, a method for improving or maintaining cognitive function in an individual comprises administering to the individual a composition comprising a combination of curcumin and an omega-3 fatty acid.

[0082]

[0080] In one embodiment, the individual does not have a cognitive impairment. For example, the composition can enhance cognitive function in a subject with normal cognitive function.

[0083]

[0081] The compositions disclosed herein can also be used to treat any of a variety of additional diseases and conditions in which a defect or reduction in mitochondrial activity is involved in the pathophysiology of a disease or condition, or in which an increase in mitochondrial function produces a desired beneficial effect. Non-limiting examples of such conditions include male infertility due to reduced sperm motility, hearing loss, macular degeneration, and other age-related and hereditary eye disorders, as well as hearing loss (e.g., age-related hearing loss).

[0084]

[0082] In each of the compositions and methods disclosed herein, the combination of curcumin and omega-3 fatty acids may be administered as a composition which is a food product comprising a food additive, food ingredient, functional food, dietary supplement, medical food, nutraceutical, or nutritional supplement.

[0085]

[0083] In one embodiment, the composition further comprises one or more medium-chain triglycerides, such as caproic acid, caprylic acid, capric acid, and lauric acid. In one embodiment, the composition further comprises phospholipids, such as phosphatidylcholine.

[0086]

[0084] In one embodiment, the composition further comprises a protein source, preferably purified protein (i.e., protein isolated from a natural food component from which it was produced). The protein content of the composition is preferably 20 to 99% by weight of the composition, for example, 20 to 90% by weight of the composition, for example, 30 to 80% by weight of the composition, for example, 40 to 80% by weight of the composition, for example, 50 to 80% by weight of the composition, for example, 40 to 70% by weight of the composition.

[0087]

[0085] Non-limiting examples of proteins or sources thereof suitable for use in the composition include hydrolyzed, partially hydrolyzed, or unhydrolyzed proteins or protein sources. These may be derived from any known or other suitable sources such as milk (e.g., casein, whey), animals (e.g., meat, fish), grains (e.g., rice, corn), or vegetables (e.g., soybeans, peas). Sources or combinations of multiple proteins may be used. Non-limiting examples of proteins or sources thereof include intact pea protein, intact pea protein isolate, intact pea protein concentrate, milk protein isolate, milk protein concentrate, casein protein isolate, casein protein concentrate, whey protein concentrate, whey protein isolate, sodium caseinate or calcium caseinate, whole milk, partially or completely skimmed milk, yogurt, soy protein isolate, and soy protein concentrate, as well as combinations thereof. Sources or combinations of multiple proteins may be used. Preferred proteins include pea protein, whey protein, soy protein, and casein. Casein protein may include, for example, sodium caseinate and calcium caseinate.

[0088]

[0086] The protein source may be provided by individual amino acids, polypeptides containing amino acids, or mixtures thereof. In many muscle growth, muscle maintenance, and / or muscle enhancement treatments, certain amino acids that are beneficial are, for example, L-arginine, L-glutamine, lysine, and branched-chain amino acids (i.e., leucine, isoleucine, and valine; leucine and isoleucine in particular). These particular amino acids may be provided as a protein source or added to the main source of protein. Thus, the protein source in the composition may include one or more branched-chain amino acids (leucine, isoleucine, and valine), one or both of L-arginine and L-glutamine, and lysine. In a preferred embodiment, the composition includes whey protein and / or casein protein together with one or more of each amino acid, for example, one or more (or all) of leucine, isoleucine, and L-arginine.

[0089]

[0087] The composition may be administered at least one day a week, preferably at least two days a week, more preferably at least three or four days a week (e.g., every other day), most preferably at least five days a week, six days a week, or seven days a week. The duration of administration may be at least one week, preferably at least one month, more preferably at least two months, most preferably at least three months, for example, at least four months. In one embodiment, administration is at least daily, for example, the subject may be administered once or more times a day. In some embodiments, administration continues for the remainder of the individual's life. In another embodiment, administration is continued until there are no detectable symptoms of the medical condition. In certain embodiments, administration is continued until there is a detectable improvement in at least one symptom, and in further cases, it is continued to maintain remission.

[0090]

[0088] The compositions disclosed herein may be administered to subjects orally, enterally, or parenterally. Non-limiting examples of parenteral administration include intravenous, intramuscular, intraperitoneal, subcutaneous, intra-articular, intra-sacral, intraocular, intrathecal, topical, and inhalation. Non-limiting examples of the form of the compositions include natural foods, processed foods, natural fruit juices, concentrates and extracts, injections, microcapsules, nanocapsules, liposomes, ointments, inhalation forms, nasal sprays, nasal solutions, eye drops, sublingual tablets, and sustained-release formulations.

[0091]

[0089] The compositions disclosed herein may be used in any of a variety of formulations for therapeutic administration. More specifically, the pharmaceutical compositions may include a suitable pharmaceutically acceptable carrier or diluent and may be formulated as solid, semi-solid, liquid or gaseous formulations such as tablets, capsules, powders, granules, ointments, solutions, suppositories, injections, inhalants, gels, microspheres, and aerosols. Accordingly, administration of the compositions can be achieved in a variety of ways, including oral, buccal, rectal, parenteral, intraperitoneal, intradermal, transdermal, and intratracheal administration. The active agent may be systemic after administration, or may be localized by topical administration, intramural administration, or by implantation that acts to retain an effective dose at the implantation site.

[0092]

[0090] In pharmaceutical dosage forms, the compounds may be administered as pharmaceutically acceptable salts. These may also be used in appropriate association with other pharmaceutically active compounds. The following methods and excipients are merely illustrative and not limiting.

[0093]

[0091] In oral formulations, the compound can be used alone or in combination with appropriate additives for manufacturing tablets, powders, granules or capsules, for example, with conventional additives such as lactose, mannitol, corn starch or potato starch; with binders such as crystalline cellulose, cellulose functional derivatives, gum arabic, corn starch or gelatin; with disintegrants such as corn starch, potato starch or sodium carboxymethylcellulose; with lubricants such as talc or magnesium stearate; and optionally in combination with diluents, buffers, wetting agents, preservatives and flavoring agents.

[0094]

[0092] The compound can be formulated as an injectable preparation by dissolving, suspending, or emulsifying it in an aqueous or non-aqueous solvent, for example, with vegetable oil or other similar oils, synthetic aliphatic acid glycerides, esters of higher aliphatic acids, or propylene glycol, and optionally together with conventional additives such as solubilizers, isotonic agents, suspending agents, emulsifiers, stabilizers, and preservatives.

[0095]

[0093] The compound can be used in aerosol formulations administered by inhalation. For example, the compound can be incorporated into pressurized, acceptable propellants such as dichlorodifluoromethane, propane, and nitrogen.

[0096]

[0094] Furthermore, the compound can be prepared as a suppository by mixing it with various bases such as emulsifying agents or water-soluble bases. The compound can be administered rectally by suppository. The suppository may contain a vehicle that melts at body temperature but solidifies at room temperature, such as cocoa butter, carbowax, and polyethylene glycol.

[0097]

[0095] Unit dosage forms for oral or rectal administration, such as syrups, elixirs, and suspensions, may be provided, and each dosage unit, e.g., one teaspoon, one tablespoon, a tablet, or a suppository, contains a specified amount of the composition. Similarly, unit dosage forms for injection or intravenous administration may contain the compound in the composition as a solution in sterile water, physiological saline, or another pharmaceutically acceptable carrier, and each dosage unit, e.g., mL or L, contains a specified amount of the composition containing one or more of the compounds.

[0098]

[0096] The disclosure also provides a kit comprising curcumin and omega-3 fatty acids in one or more containers. In some embodiments, one or more of these compounds may be isolated compounds.

[0099]

[0097] In one embodiment of the kit, curcumin and omega-3 fatty acids may be provided together as one or more pre-packaged unit dosage forms, for example, as separate containers each containing a dry powder, such that each container contains one pre-packaged unit dosage form.

[0100]

[0098] In another embodiment, the kit may include a plurality of compositions to be mixed together to form one or more compositions disclosed herein. For example, the kit may contain two or more dry powders in separate containers from each other, each of which contains a portion of the final unit dosage form. In a non-limiting example of such an embodiment, the kit may include one or more first containers containing curcumin, and also include one or more second containers containing omega-3 fatty acids. The contents of one of the first containers may be mixed with one of the second containers to form at least a portion of the unit dosage forms of the compositions.

[0101]

[0099] Example

[0100] The following non-limiting examples present scientific data that develop and support the concept that administering a combination of curcumin and omega-3 fatty acids increases cellular energy production, thereby improving the age-related decline in function of different tissues, such as muscles.

[0102]

[0101] Aged rats are a good model for evaluating the effects of nutritional interventions on age-related decline. In this model used by the inventors, 20-month-old rats were fed for one month either a normal diet or a similar diet supplemented with curcumin or n-3 fatty acids (n-3 FA) alone or in combination. Citrate synthase and mitochondrial respiratory chain complex activity, measured by colorimetric method, were synergistically enhanced in the curcumin and n-3 FA groups, suggesting improved mitochondrial energy production. Simultaneously, the MFN2 / DRP1 expression ratio (mitochondrial fusion / fission), measured by Western blotting, showed a synergistic increase in the same treatment group (Figures 1-3).

[0103]

[0102] Figure 1 shows the effects of curcumin (CUR), n-3 fatty acid (OM3), and a combination of both (CUR+OM3) on mitochondrial complex activity in aged rats. 20-month-old rats were fed either a control diet or a similar diet supplemented with curcumin, n-3 fatty acid, or a combination of both for one month. Results are expressed as mean ± standard error. CON: control diet. CUR: control diet containing curcumin. OM3: control diet containing n-3 fatty acid. CUR+OM3: control diet containing curcumin and n-3 fatty acid.

[0104]

[0103] Figure 2 shows the effects of curcumin (CUR), n-3 fatty acid (OM3), and a combination of both (CUR+OM3) on citrate synthase activity in aged rats. 20-month-old rats were fed either a control diet or a similar diet supplemented with curcumin, n-3 fatty acid, or a combination of both for one month. Results are expressed as mean ± standard error. CON: control diet. CUR: control diet containing curcumin. OM3: control diet containing n-3 fatty acid. CUR+OM3: control diet containing curcumin and n-3 fatty acid.

[0105]

[0104] Figure 3 shows the effects of curcumin (CUR), n-3 fatty acid (OM3), and a combination of both (CUR+OM3) on the MFN2 / DRP1 expression ratio in aged rats. 20-month-old rats were fed either a control diet or a similar diet supplemented with curcumin, n-3 fatty acid, or a combination of both for one month. Results are expressed as mean ± standard error. CON: control diet. CUR: control diet containing curcumin. OM3: control diet containing n-3 fatty acid. CUR+OM3: control diet containing curcumin and n-3 fatty acid.

[0106]

[0105] It should be understood that various changes and modifications to the current preferred embodiments described herein will be apparent to those skilled in the art. Such changes and modifications can be made without departing from the spirit and scope of the subject matter of the invention and without impairing the intended advantages. Therefore, such changes and modifications are intended to be covered by the appended claims.

Claims

1. A combination of curcumin and omega-3 fatty acids in an amount effective for improving or maintaining mitochondrial function by enhancing mitochondrial respiratory chain complex activity, A composition in a unit dosage form, administered for the purpose of (vii) in an amount that provides 500 mg to 5 g of the omega-3 fatty acid and 0.01 mg to 2.0 g of the curcumin per day.

2. The composition according to claim 1, wherein the combination of the amounts is effective in treating, reducing the incidence of, or reducing the severity of, mitochondrial-related diseases or conditions selected from the group consisting of stress, obesity, diabetes mellitus, complications of diabetes, hyperlipidemia, neurodegenerative diseases, cognitive impairment, stress-induced or stressor-related cognitive dysfunction, mood disorders, anxiety disorders, age-related neuronal cell death or dysfunction, infections, hearing loss, and combinations thereof.

3. The composition according to claim 1 or 2, which is a food product, a dietary supplement, or a nutraceutical.

4. A combination of curcumin and omega-3 fatty acids in an amount effective for improving or maintaining mitochondrial function by enhancing mitochondrial respiratory chain complex activity, contained in one or more containers, A kit in which the combination is administered for the purpose of (vii) in an amount that provides 500 mg to 5 g of the omega-3 fatty acid and 0.01 mg to 2.0 g of the curcumin per day.

5. The kit according to claim 4, wherein the one or more containers include at least one first container that contains the curcumin separately from the omega-3 fatty acids contained in at least one second container, and the kit further includes instructions for mixing the curcumin with the omega-3 fatty acids into unit dosage forms.

6. The kit according to claim 4, wherein each of the one or more containers contains a unit dosage form of the combination of curcumin and the omega-3 fatty acid.

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