Composition for improving, suppressing reduction of, or maintaining energy

Abstract

The purpose of the present invention is to provide a composition that can improve, suppress reduction of, or maintain energy production, that is effective in improving, suppressing reduction of, or maintaining energy production, and that is highly safe and can be ingested continuously. The present invention relates to a composition for improving, suppressing reduction or, or maintaining energy production that contains as active ingredients the following components (A) and (B): (A) sesamin compounds and (B) astaxanthin compounds, in which the weight ratio ((A) / (B)) of component (A) (in terms of sesamin) to component (B) (in terms of astaxanthin) is 0.05 to 15.

Description

Composition for improving, preventing or maintaining the decline of energy production

[0001] The present invention relates to a composition for improving energy production, suppressing a decrease in energy production, or maintaining the same. The present invention also relates to a method for improving energy production, suppressing a decrease in energy production, or maintaining the same.

[0002] Energy production refers to the production of energy necessary for humans and non-human animals to maintain their activities. Most energy production occurs within mitochondria, a type of intracellular organelle. Sugars, lipids, amino acids, and other nutrients ingested from food are metabolized through glycolysis, the pentose phosphate pathway, and the citric acid cycle and converted into nicotinamide adenine dinucleotide (NADH). Next, electrons from NADH are transferred to mitochondrial respiratory chain proteins (electron transport chain), producing energy in the form of adenosine triphosphate (ATP). Reduced ATP production is known to cause various problems in humans, including obesity due to decreased metabolic capacity, increased risk of diabetes, decreased muscle strength, increased fatigue, lethargy, decreased concentration, and depression.

[0003] Maintaining ATP production is important for reducing fatigue, maintaining concentration, exercising using muscles, and maintaining mental and physical vitality.

[0004] To date, various energy production enhancers containing carbohydrates, amino acids, and lipids, which are substrates necessary for ATP production, have been known (Patent Document 1).

[0005] As mentioned above, the substrates necessary for ATP production are converted to ATP via the mitochondrial electron transport system, but even if the substrates increase, ATP cannot be produced if mitochondrial function is impaired. It is known that impaired mitochondrial function is caused by aging and oxidative stress, resulting in a decrease in ATP production (Non-Patent Documents 1 and 2).

[0006] When taking a supplement containing an ingredient that suppresses a decline in energy production or mitochondrial dysfunction, it is desirable for the supplement to be in a form that is easy for consumers to take continuously. For elderly people in particular, as their swallowing function declines, it is desirable for tablets and capsules to be small. Since tablets and capsules tend to be large in volume, especially when multiple ingredients are included, it is desirable to use an ingredient or combination of ingredients that is highly effective even in small amounts in order to reduce the volume of the tablet or capsule.

[0007] Sesamin is a lignan compound found in sesame and has been reported to have antioxidant properties. It has been reported that sesamin has an antioxidant effect that inhibits mitochondrial dysfunction in diabetic model mice (Non-Patent Document 3). Furthermore, sesamin is known to inhibit mitochondrial reactive oxygen production and mitochondrial membrane potential decline through its antioxidant properties (Non-Patent Document 4). It has also been reported that sesamin activates PGC1α, which is involved in mitochondrial biogenesis (Patent Document 2).

[0008] Astaxanthin is a type of carotenoid and is known to have antioxidant properties.

[0009] JP 2009-215170 A International Publication No. 2018 / 079719

[0010] Conley, Kevin E. , et al. “Oxidative capacity and aging in human muscle.” The Journal of physiology 526.1 (2000): 203-210. Kudryavtseva, Anna V. , et al. “Mitochondrial dysfunction and oxidative stress in aging and cancer.” Oncotarget 7.29 (2016): 44879. Takada, Shingo, et al. “Sesamin prevents decline in exercise capacity and impairment of skeletal muscle mitochondrial function in mice with ” Experimental physiology 100.11 (2015): 1319-1330. Maharjan, Sunita, et al. “Mitochondrial impairment triggers cytosolic oxidative stress and cell death following proteasome inhibition.” Scientific reports 4 (2014): 5896.

[0011] Since energy is constantly required to maintain activity in humans and other organisms, a highly safe method for promoting energy production using ingredients that can be taken continuously without the risk of side effects is desired. Conventionally, methods for increasing energy production by ingesting energy production substrates have been proposed, but the effects cannot be fully enjoyed when mitochondrial function is impaired. Furthermore, while food ingredients that have the effect of improving energy production are known, from the standpoint of ease of intake and safety when taken continuously, it is desirable to have an ingredient or combination of ingredients that is effective even in small amounts.

[0012] An object of the present invention is to provide a composition that is effective in improving energy production, suppressing a decrease in energy production, or maintaining energy production, and that is highly safe and can be taken continuously.

[0013] The present inventors conducted extensive research to solve the above problems and investigated components that can be used to improve energy production, prevent its decline, or maintain energy production. They found that combining a sesamin-class compound with an astaxanthin-class compound in a specific weight ratio can improve energy production, prevent its decline, or maintain energy production more effectively (synergistically) than using either a sesamin-class compound or an astaxanthin-class compound alone.

[0014] The present invention relates to the following compositions for improving, suppressing a decline in, or maintaining energy production. [1] A composition for improving, suppressing a decline in, or maintaining energy production, comprising the following active ingredients: (A) a sesamin-class compound and (B) an astaxanthin-class compound, wherein the weight ratio ((A) / (B)) of component (A) (converted to sesamin) to component (B) (converted to astaxanthin) is 0.05 to 15. [2] The composition according to [1] above, which is used to suppress, alleviate, or ameliorate fatigue or tiredness associated with aging. [3] The composition according to [1] or [2] above, wherein the improvement, suppression of a decline, or maintenance of energy production is mediated by the improvement, suppression of a decline, or maintenance of mitochondrial function. [4] The composition according to any of [1] to [3] above, wherein the sesamin-class compound is at least one compound selected from the group consisting of sesamin, episesamin, and metabolites thereof. [5] The composition according to any one of [1] to [4] above, wherein the astaxanthin-related compound is at least one compound selected from the group consisting of astaxanthin and derivatives thereof. [6] The composition according to any one of [1] to [5] above, wherein the astaxanthin-related compound is derived from a Haematococcus algae extract. [7] The composition according to any one of [1] to [6] above, which is an oral composition. [8] The composition according to any one of [1] to [7] above, which is a food or drink. [9] The composition according to any one of [1] to [8] above, which is used for people who experience strong feelings of fatigue in their daily lives.

[10] The composition according to any one of [1] to [9] above, which is used in combination with exercise.

[11] The composition according to any one of [1] to

[10] above, which is labeled with one or more indications selected from the group consisting of "aids energy production or metabolism," "aids cellular energy production or metabolism," "aids energy production or metabolism in intracellular mitochondria," "maintains and improves vitality and energy," "reduces fatigue associated with aging," "reduces fatigue associated with aging," "for those who become more susceptible to fatigue with age," "reduces fatigue that has become more noticeable with age," "reduces fatigue experienced in daily life," "reduces fatigue in daily life," "reduces general malaise," "reduces lethargy," "reduces feelings of weakness," "reduces discomfort," "suppresses a decrease in motivation to be active," and "prevents muscle function decline."

[12] A method for improving energy production and suppressing a decrease in or maintaining it, comprising administering a composition containing the following components (A) and (B): (A) a sesamin-class compound and (B) an astaxanthin-class compound, wherein the weight ratio ((A) / (B)) of component (A) (converted to sesamin) to component (B) (converted to astaxanthin) is 0.05 to 15.

[13] Use of a composition containing the following components (A) and (B): (A) a sesamin-class compound and (B) an astaxanthin-class compound, wherein the weight ratio ((A) / (B)) of component (A) (converted to sesamin) to component (B) (converted to astaxanthin) is 0.05 to 15, for improving energy production and suppressing a decrease in or maintaining it.

[0015] According to the present invention, it is possible to provide a composition that is effective in improving energy production, suppressing a decrease in energy production, or maintaining energy production, and that is highly safe and can be taken continuously.

[0016] The composition of the present invention for improving, suppressing a decrease in, or maintaining energy production contains a sesamin-class compound as component (A) and an astaxanthin-class compound as component (B). The composition of the present invention for improving, suppressing a decrease in, or maintaining energy production contains a sesamin-class compound and an astaxanthin-class compound as active ingredients. Energy production refers to the production of energy necessary for humans or non-human animals to maintain activity.

[0017] (Component (A): Sesamin-related Compounds) In the present invention, "sesamin-related compounds" refers to compounds including sesamin and its analogs. A single compound or two or more compounds may be used as the sesamin-related compounds. Sesamin is one of the major lignan compounds found in sesame. Examples of sesamin-related compounds include episesamin and the dioxabicyclo[3.3.0]octane derivatives described in Japanese Patent Application Laid-Open No. 4-9331. Specific examples of sesamin-related compounds include sesamin, episesamin, sesaminol, episesaminol, sesamol, and sesamolin. These stereoisomers or racemates may be used alone or in mixtures. Furthermore, sesamin metabolites (e.g., those described in Japanese Patent Application Laid-Open No. 2001-139579) are also sesamin-related compounds included in the sesamin-related compounds of the present invention, and can be used in the present invention, so long as they exhibit the effects of the present invention. In the present invention, sesamin, episesamin, or metabolites thereof can be suitably used as sesamin-class compounds. When sesamin and episesamin are used, the ratio thereof is not particularly limited, but for example, the sesamin:episesamin (weight ratio) is preferably 1:0.1 to 1:9, more preferably 1:0.3 to 1:3, and even more preferably 1:0.5 to 1:2. A form in which the weight ratio of sesamin:episesamin is 1:1 is one preferred embodiment of the present invention. Examples of metabolites that can be used as sesamin-class compounds include the compounds described in JP 2009-143884 A. As sesamin metabolites, SC1 ((7α,7'α,8α,8'α)-3',4'-methylenedioxy-7,9':7',9-diepoxylignane-3,4-diol) and SC2 ((7α,7'α,8α,8'α)-7,9':7',9-diepoxylignane-3,3',4,4'-tetraol) are preferred. As a sesamin metabolite, SC1 is more preferred.

[0018] The sesamin-class compounds used in the present invention are not limited by their form or production method. For example, in the case of sesamin, sesamin (referred to as sesamin extract or purified product) extracted from sesame oil by known methods (e.g., the method described in Japanese Patent Application Laid-Open No. 4-9331) can be used. Alternatively, commercially available sesame oil (liquid) can be used as is. However, when sesame oil is used, the characteristic flavor of sesame oil can be perceived as sensorily undesirable. Therefore, it is preferable to use a tasteless and odorless sesamin extract (or purified sesamin product) extracted from sesame oil. Furthermore, when sesame oil is used, the sesamin content is low, and if a desired amount of sesamin is to be incorporated, the volume per unit dose of the formulated composition becomes too large, which can cause ingestion problems. In particular, when formulated for oral ingestion, the formulation (tablet, capsule, etc.) becomes too large, hindering ingestion. Therefore, from the viewpoint of requiring a small intake amount, it is preferable to use a sesamin extract (or purified sesamin product) from sesame oil. Sesamin-related compounds can also be obtained by synthesis. For example, sesamin and episesamin can be synthesized by the method of Beroza et al. (J. Am. Chem. Soc., 78, 1242 (1956)). Sesamin-related compounds can also be produced by the method described in JP 2009-143884 A, for example.

[0019] (Component (B): Astaxanthin-related Compounds) In the present invention, astaxanthin-related compounds are a general term for compounds containing astaxanthin and its derivatives. As the astaxanthin-related compounds, one type of compound may be used, or two or more types of compounds may be used. Astaxanthin (3,3'-dihydroxy-β,β-carotene-4,4'-dione) is a type of carotenoid, and is a red pigment found in crustaceans such as shrimp and crab, fish such as salmon and sea bream, algae such as the green algae Haematococcus, and yeasts such as the red yeast Phaffia. Astaxanthin exists in three isomers: the 3S,3'S isomer, the 3S,3'R isomer (meso isomer), and the 3R,3'R isomer, depending on the configuration of the hydroxyl groups at the 3 (3') positions of the ring structures at both ends of the molecule. Furthermore, geometric isomers also exist, with the conjugated double bond at the center of the molecule being cis or trans. Specific examples of geometric isomers include all-trans isomers, 9-cis isomers, and 13-cis isomers. Astaxanthin may be any one of these compounds, or two or more of these compounds.

[0020] The astaxanthin derivative is not particularly limited, and may be any compound in which a substituent or the like is bonded to a functional group possessed by astaxanthin, such as an ester. The hydroxyl group at the 3 (3') position of astaxanthin can form an ester with a fatty acid, and astaxanthin esters include monoesters and diesters. Hydrolysis of an astaxanthin ester produces astaxanthin. The fatty acid that forms the ester is not particularly limited, but the number of carbon atoms in the fatty acid is preferably 1 to 30. In the present invention, astaxanthin and astaxanthin esters are preferred as astaxanthin-like compounds.

[0021] The astaxanthin compound used in the present invention is not limited in any way by its form or production method. Natural astaxanthin compounds and synthetic astaxanthin compounds can be used. Examples of natural astaxanthin compounds include those derived from algae such as Haematococcus; yeasts such as Phaffia; crustaceans such as shrimp, krill, and crab; cephalopods such as squid and octopus; various seafood; plants such as Adonis; bacteria such as Paracoccus sp. N81106, Brevundimonas sp. SD212, and Erythrobacter sp. PC6; actinomycetes such as Gordonia sp. KANMONKAZ-1129; and Schizochytriuym sp. Examples of astaxanthin-containing compounds include extracts containing astaxanthin compounds obtained from Labyrinthulea species such as KH105; fungi such as Blakeslea trispora; astaxanthin-producing genetically modified organisms; and astaxanthin compounds appropriately purified from the extracts containing astaxanthin compounds.Preferably, astaxanthin compounds derived from microalgae extracts extracted from microalgae such as Haematococcus, and astaxanthin compounds derived from fungal extracts extracted from fungi such as Blakeslea trispora, and more preferably, astaxanthin compounds derived from Haematococcus algae extracts extracted from Haematococcus algae.Furthermore, examples of synthetic astaxanthin compounds include AstaSana (DSM) and Lucantin Pink (registered trademark) (BASF). Furthermore, examples of synthetic astaxanthin-related compounds obtained by chemically converting other naturally occurring carotenoids include AstaMarine (PIVEG).

[0022] Examples of Haematococcus algae from which natural astaxanthin-class compounds can be obtained include Haematococcus pluvialis, Haematococcus lacustris, Haematococcus capensis, Haematococcus deroebakensis, and Haematococcus zimbabwiensis.

[0023] The method for culturing the above-mentioned Haematococcus algae is not particularly limited, but a sealed culture method is preferred, which does not introduce or grow foreign microorganisms and is less likely to introduce other contaminants. Examples of such culture methods include a culture method using a partially open dome-shaped, conical, or cylindrical culture device and a culture medium having a gas discharge device that can be moved freely within the device (WO 1999 / 050384), a method in which Haematococcus algae are subjected to desiccation stress to induce encystment of the algae and astaxanthin is collected from a culture of the encysted algae (JP 8-103288 A), a method in which a light source is placed in a sealed culture device and light is irradiated from the inside to carry out culture, and a method using a flat culture tank or a tubular culture layer.

[0024] The astaxanthin-related compounds that can be used in the present invention may be, for example, an astaxanthin-related compound-containing extract obtained by disrupting the cell walls of the above-mentioned Haematococcus algae, if necessary, according to the method disclosed in JP-A-5-068585, and then adding an extraction solvent or solvent such as acetone, ether, chloroform, or alcohol (ethanol, methanol, etc.), or supercritical carbon dioxide, or this astaxanthin-related compound-containing extract may be appropriately purified as necessary and then incorporated into the composition. The astaxanthin-related compound content of the astaxanthin-related compound-containing extract is preferably 3 to 40 wt%, more preferably 3 to 12 wt%, and even more preferably 5 to 10 wt%.

[0025] In the present invention, examples of the astaxanthin-related compounds include commercially available products such as AstaReal Oil 200SS (a fat-soluble extract from Haematococcus algae, containing approximately 20% astaxanthin-related compounds in terms of free form), AstaReal L10, AstaReal Oil 50F, AstaReal Oil 50FC, AstaReal Oil 5F, and AstaReal AstaReal, Astavita, and Astamate series such as P2AF, AstaTROL-X, AstaReal Oil 50FC, AstaReal Powder 20F, Water-soluble AstaReal Liquid, AstaReal WS Liquid, AstaReal 10WS Liquid, AstaReal ACT, Astavita e, Astavita Sports, and Astamate (all registered trademarks; manufactured by AstaReal Co., Ltd. and Fuji Chemical Industry Co., Ltd.); ASTOTS series such as ASTOTS-S, ASTOTS-10O, ASTOTS-ECS, ASTPTS-2.0PW, and ASTOTS-3.0MB (all ASTOTS are registered trademarks; manufactured by Fujifilm Wako Pure Chemical Industries Co., Ltd.); BioAstin (registered trademark; Cyanotec Corporation); Astazine™ (BGG Examples of suitable astaxanthin extracts include astaxanthin powder 1.5%, astaxanthin powder 2.5%, astaxanthin oil 5%, and astaxanthin oil 10% (manufactured by Bioactives Japan); astaxanthin (Oryza Oil & Fat Chemical Co., Ltd.); Sunactive AX (registered trademark; manufactured by Taiyo Kagaku Co., Ltd.); Haematococcus WS30 (manufactured by Yaegaki Fermentation Engineering Co., Ltd.); and AstaMarine (manufactured by PIVEG).

[0026] Sesamin-related compounds and astaxanthin-related compounds are found in natural products and foods and beverages, have a long history of consumption, and are recognized as being highly safe. Therefore, sesamin-related compounds and astaxanthin-related compounds are suitable for continuous and long-term intake.

[0027] The composition of the present invention contains a sesamin-class compound (component (A)) and an astaxanthin-class compound (component (B)) as active ingredients, and the weight ratio ((A) / (B)) of component (A) (in terms of sesamin) to component (B) (in terms of astaxanthin) is 0.05 to 15. By combining a sesamin-class compound and an astaxanthin-class compound in the above weight ratio, significantly excellent effects can be obtained in improving energy production and inhibiting its decline or maintaining it. The weight ratio of component (A) (in terms of sesamin) to component (B) (in terms of astaxanthin) is preferably 0.08 to 12, more preferably 0.1 to 12, even more preferably 0.12 to 10, and particularly preferably 0.15 to 9. When the sesamin-class compound is a compound other than sesamin, the value is converted to sesamin. More specifically, in this specification, the term "amount in terms of sesamin equivalent" or similar expressions refers to the amount of sesamin-related compound when the sesamin-related compound is sesamin, and when the sesamin-related compound is a compound other than sesamin, refers to the value obtained by multiplying the number of moles of the compound by the molecular weight of sesamin. Furthermore, the term "astaxanthin equivalent" refers to the value obtained by converting the astaxanthin-related compound to astaxanthin when the astaxanthin-related compound is a compound other than astaxanthin. More specifically, in this specification, the term "amount in terms of astaxanthin equivalent" or similar expressions refers to the amount of astaxanthin when the astaxanthin-related compound is astaxanthin, and when the astaxanthin-related compound is a compound other than astaxanthin, refers to the value obtained by multiplying the number of moles of the compound by the molecular weight of astaxanthin. The content of sesamin-related compounds and astaxanthin-related compounds in the above composition can be measured by HPLC (high performance liquid chromatography). Furthermore, when the astaxanthin-class compound is a derivative of astaxanthin, it can be quantified as astaxanthin by subjecting it to a treatment such as hydrolysis.

[0028] Most energy production in living organisms occurs within mitochondria. Improving, inhibiting the decline, or maintaining mitochondrial function can improve, inhibit the decline, or maintain energy production. The composition for improving, inhibiting the decline, or maintaining energy production of the present invention can be used, for example, to improve, inhibit the decline, or maintain energy production through improving, inhibiting the decline, or maintaining mitochondrial function. The composition of the present invention can also activate energy metabolism by improving, inhibiting the decline, or maintaining mitochondrial function. In one aspect, the composition of the present invention can be used as a composition for improving, inhibiting the decline, or maintaining energy production through improving, inhibiting the decline, or maintaining mitochondrial function. In one aspect, the composition of the present invention can be used for improving, inhibiting the decline, or maintaining energy production capacity.

[0029] Improving, inhibiting, or maintaining mitochondrial function and / or energy production is effective in inhibiting, alleviating, or ameliorating fatigue. As used herein, fatigue refers to a decrease in physical activity capacity and / or a decrease in mental vitality (a decrease in activity capacity due to mental and physical overload) caused by physical or mental factors. Fatigue is usually accompanied by a sense of fatigue (a subjective sense of fatigue, such as discomfort or decreased motivation to be active). Anti-fatigue refers to inhibiting, alleviating, or ameliorating fatigue. Inhibiting fatigue includes increasing fatigue tolerance and preventing fatigue (including reducing the risk in subjects at risk of fatigue). Reducing fatigue includes alleviating fatigue symptoms (e.g., fatigue, etc.). Improving fatigue includes recovering from fatigue and ameliorating fatigue symptoms. Energy production, in particular, tends to decrease with age. As a result, fatigue tends to become more common, fatigue recovery is delayed, and fatigue tends to become a normal part of life. The composition of the present invention can be preferably used to suppress, reduce, or ameliorate age-related fatigue or tiredness by improving, inhibiting a decline, or maintaining mitochondrial function and / or energy production. Age-related fatigue or tiredness includes fatigue or tiredness that becomes more easily felt in daily life with age. In one aspect, the composition of the present invention can be preferably used to suppress, reduce, or ameliorate age-related fatigue. The composition of the present invention can be used to suppress, reduce, or ameliorate physical fatigue and / or mental fatigue that becomes more easily felt with age, to suppress, reduce, or ameliorate physical fatigue and / or mental fatigue that becomes more easily felt with age, and to suppress, reduce, or ameliorate fatigue in daily life that becomes more easily felt with age, and in particular, can be preferably used to suppress, reduce, or ameliorate fatigue and / or tiredness that becomes more easily felt in daily life with age.

[0030] Using a sesamin-class compound and an astaxanthin-class compound in the above weight ratio can synergistically enhance the effects of improving, inhibiting, or maintaining energy production, and improving, inhibiting, or maintaining mitochondrial function. When a sesamin-class compound and an astaxanthin-class compound are combined in the above weight ratio and used as an active ingredient for improving, inhibiting, or maintaining energy production, or for inhibiting, reducing, or improving fatigue or tiredness associated with aging, the above effects can be achieved even with a low dose of the active ingredient, making it possible to reduce the intake amount of the active ingredient. Reducing the intake amount leads to easier intake, allowing for the production of anti-fatigue compositions, compositions for improving, inhibiting, or maintaining energy production, and the like that are easier to take continuously.

[0031] In this specification, energy production may be evaluated based on common knowledge in the technical field to which the present invention pertains, and the method for evaluating it is not particularly limited. For example, energy production can be evaluated by continuously measuring the oxygen consumption rate (OCR) used by mitochondria during ATP synthesis in the cells being measured using an extracellular flux analyzer while adding an ATP synthase inhibitor (e.g., oligomycin and rotenone) and an uncoupler (e.g., carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP)). Energy production can be evaluated by analyzing, for example, basal respiration, ATP production, or maximum respiration, which are considered to be major indicators in evaluating energy production. Mitochondrial function can also be evaluated by the above evaluation.

[0032] The composition of the present invention can be in the form of a food or beverage, a pharmaceutical product, a quasi-drug, a feed, etc. The composition of the present invention may itself be a food or beverage, a pharmaceutical product, a quasi-drug, a feed, etc. for improving, inhibiting or maintaining a decline in energy production, or for inhibiting, reducing or improving fatigue or fatigue sensations associated with aging, or may be a material or preparation to be used in combination with these. The composition of the present invention can be provided in the form of a preparation, for example, but is not limited to this form. The preparation can also be provided as a composition as is, or as a composition containing the preparation. The composition of the present invention may be either an oral composition or a parenteral composition, but is preferably an oral composition. Oral compositions include food or beverages, oral pharmaceutical products, quasi-drugs, and feed, preferably food or beverages or oral pharmaceutical products, and more preferably food or beverages.

[0033] The composition of the present invention can contain any additives and ingredients in addition to the sesamin-class compounds and astaxanthin-class compounds, as long as the effects of the present invention are not impaired. These additives and ingredients can be selected depending on the form of the composition, and those that can generally be used in foods and beverages, pharmaceuticals, quasi-drugs, feed, etc. can be used. When the composition of the present invention is used as a food and beverage, pharmaceutical, quasi-drug, feed, etc., the manufacturing method thereof is not particularly limited, and it can be manufactured by a general method.

[0034] For example, when the composition of the present invention is used as a food or beverage, various foods and beverages can be prepared by blending the sesamin-class compound and astaxanthin-class compound with ingredients that can be used in foods and beverages (e.g., food ingredients, food additives used as needed, etc.). The foods and beverages are not particularly limited, and examples include general foods and beverages, health foods, health drinks, functional foods, foods for specified health uses, health supplements, and foods and beverages for patients. The health foods, functional foods, foods for specified health uses, health supplements, and the like can be used in various dosage forms, such as fine granules, tablets, granules, powders, capsules, chewable tablets, dry syrups, syrups, liquids, beverages, and liquid diets.

[0035] When the composition of the present invention is used as a pharmaceutical or quasi-drug, it can be formulated into various dosage forms by blending the sesamin-class compound and astaxanthin-class compound with a pharmacologically acceptable carrier and, if necessary, additives. Such carriers, additives, etc. may be any pharmacologically acceptable carriers that can be used in pharmaceuticals or quasi-drugs, and may include, for example, one or more of excipients, binders, disintegrants, lubricants, antioxidants, colorants, etc. The pharmaceutical or quasi-drug administration form (ingestion) may be oral or parenteral (transdermal, transmucosal, enteral, injection, etc.) administration form. When the composition of the present invention is used as a pharmaceutical or quasi-drug, it is preferably an oral pharmaceutical or quasi-drug. Dosage forms for oral administration include liquids, tablets, powders, fine granules, granules, sugar-coated tablets, capsules, suspensions, emulsions, chewable tablets, etc. The pharmaceutical may also be a non-human animal drug.

[0036] When the composition of the present invention is used as feed, the sesamin-class compound and the astaxanthin-class compound may be blended into the feed. Feed also includes feed additives. Examples of feed include livestock feed for cows, pigs, chickens, sheep, horses, etc.; small animal feed for rabbits, rats, mice, etc.; and pet food for dogs, cats, small birds, etc.

[0037] The content of sesamin-class compounds in the composition of the present invention is not particularly limited and can be set depending on the form, etc. The total content of sesamin-class compounds in the composition of the present invention (in terms of sesamin) is, for example, preferably 0.001 wt % or more, more preferably 0.01 wt % or more, even more preferably 0.05 wt % or more, and preferably 10 wt % or less, more preferably 5 wt % or less. In one embodiment, the total content of sesamin-class compounds (in terms of sesamin) in the composition is preferably 0.001 to 10 wt %, more preferably 0.01 to 10 wt %, even more preferably 0.05 to 5 wt %.

[0038] The total content of astaxanthin-class compounds contained in the composition of the present invention is not particularly limited and can be set depending on the form, etc. The total content of astaxanthin-class compounds in the composition of the present invention (astaxanthin equivalent) is, for example, preferably 0.001 wt% or more, more preferably 0.01 wt% or more, even more preferably 0.05 wt% or more, and preferably 10 wt% or less, more preferably 5 wt% or less, in terms of astaxanthin equivalent. In one embodiment, the total content of astaxanthin-class compounds (astaxanthin equivalent) in the composition is preferably 0.001 to 10 wt%, more preferably 0.01 to 10 wt%, even more preferably 0.05 to 5 wt%.

[0039] The composition of the present invention is preferably taken orally (administered orally). The dosage (which can also be referred to as intake amount) of the composition of the present invention is not particularly limited. The dosage of the composition of the present invention may be an amount that can achieve the effect of improving, suppressing or maintaining the decline of energy production, improving, suppressing or maintaining the decline of mitochondrial function, and / or suppressing, reducing or improving fatigue or tiredness associated with aging, and may be appropriately determined depending on the dosage form, administration method, body weight of the subject, etc.

[0040] In one embodiment, when the composition of the present invention is orally ingested or administered to a human (adult), the total dose of sesamin-class compounds is preferably 0.5 mg or more, more preferably 1 mg or more, even more preferably 3 mg or more, and preferably 200 mg or less, more preferably 100 mg or less, and even more preferably 80 mg or less per 60 kg of body weight per day, in sesamin equivalent. The total dose of astaxanthin-class compounds is preferably 0.5 mg or more, more preferably 1 mg or more, even more preferably 3 mg or more, and preferably 200 mg or less, more preferably 100 mg or less, and even more preferably 80 mg or less per 60 kg of body weight per day, in astaxanthin equivalent. In one embodiment, the total dose of sesamin-class compounds is preferably 0.5 to 200 mg, more preferably 1 to 100 mg, and even more preferably 3 to 80 mg per 60 kg of body weight per day, in sesamin equivalent, for a human (adult). In one embodiment, sesamin and / or episesamin are orally ingested or administered to a human (adult) in a total dosage of sesamin and / or episesamin per day per 60 kg body weight, preferably 0.5 to 200 mg, more preferably 1 to 100 mg, and even more preferably 3 to 80 mg. Furthermore, the total dosage of astaxanthin-class compounds is preferably 0.5 to 200 mg, more preferably 1 to 100 mg, and even more preferably 3 to 80 mg, in terms of astaxanthin, per day per 60 kg body weight for a human (adult). The above amounts are preferably ingested or administered once or more times a day, for example, once a day, or in divided doses (e.g., 2 to 3 times a day). In one embodiment, the above amounts of sesamin-class compounds and astaxanthin-class compounds are orally ingested or administered to a human. In one embodiment, the composition of the present invention can be used to administer or cause a human to ingest the above-mentioned amounts of sesamin-class compounds and astaxanthin-class compounds per 60 kg of body weight per day. When two or more sesamin-class compounds are used, the total amount of sesamin-class compounds administered is the sum of these amounts. When two or more astaxanthin-class compounds are used, the total amount of astaxanthin-class compounds administered is the sum of these amounts.

[0041] The composition of the present invention is preferably one that is ingested or administered continuously. The above-mentioned effects are expected to be enhanced by the continuous ingestion or administration of sesamin-class compounds and astaxanthin-class compounds. In one embodiment, the composition of the present invention is preferably ingested or administered continuously for at least one week, more preferably at least four weeks, even more preferably at least eight weeks, and particularly preferably at least 12 weeks.

[0042] The subject (which may also be referred to as the administration subject) to which the composition of the present invention is administered or ingested is not particularly limited, and includes humans and non-human animals. Examples of non-human animals include industrial animals, pets, and laboratory animals. Specifically, industrial animals refer to animals that need to be raised industrially, such as livestock such as cows, horses, pigs, goats, and sheep, poultry such as chickens, ducks, quails, turkeys, and ostriches, and fish such as yellowtail, yellowtail, red sea bream, horse mackerel, carp, rainbow trout, and eels. Pets refer to so-called pets and companion animals such as dogs, cats, marmosets, small birds, and hamsters, while laboratory animals refer to animals used in research in fields such as medicine, biology, agriculture, and pharmacy, such as mice, rats, guinea pigs, beagles, minipigs, rhesus monkeys, and cynomolgus monkeys.

[0043] The subject of administration of the composition of the present invention is preferably a human or a non-human mammal, more preferably a human. In one embodiment, the subject of administration includes a subject who needs or desires to improve, inhibit decline, or maintain energy production, a subject who needs or desires to improve, inhibit decline, or maintain mitochondrial function, a subject who needs or desires to inhibit, reduce, or improve age-related fatigue or tiredness, a subject experiencing age-related fatigue, a subject who has become more susceptible to fatigue with age, a subject experiencing general malaise, lethargy, or weakness, and a subject experiencing severe daily fatigue. As described above, mitochondrial function and energy production are known to decline with age. In one embodiment, the subject of administration of the composition of the present invention is preferably middle-aged or elderly. The composition of the present invention may be an anti-fatigue composition for middle-aged or elderly people (preferably elderly people) for age-related fatigue or tiredness, a composition for inhibiting, reducing, or improving age-related fatigue or tiredness, or a composition for improving, inhibiting decline, or maintaining energy production. Middle-aged or elderly people may be, for example, humans aged 40 years or older. Middle-aged or elderly people include elderly people. The elderly may be, for example, a human aged 60 or over or 65 or over. The composition of the present invention can also be used in healthy individuals for the purpose of, for example, improving, inhibiting or maintaining mitochondrial function, improving, inhibiting or maintaining energy production, or inhibiting, alleviating or improving fatigue or tiredness associated with aging. In one aspect, the composition of the present invention is preferably used in humans who experience strong tiredness in their daily lives.

[0044] When the composition of the present invention is used in combination with moderate exercise, the effect of suppressing, reducing, or improving fatigue or a feeling of fatigue is further enhanced. In one embodiment, the composition of the present invention is preferably used in combination with exercise.

[0045] The composition of the present invention may be labeled with one or more of the following: "aids energy production or metabolism," "aids cellular energy production or metabolism," "aids energy production or metabolism in intracellular mitochondria," "maintains and improves vitality and energy," "reduces age-related fatigue," "reduces age-related fatigue," "for those who become more susceptible to fatigue with age," "reduces fatigue that has become more susceptible with age," "reduces fatigue experienced in daily life," "reduces fatigue in daily life," "reduces general malaise," "reduces lethargy," "reduces feelings of weakness," "reduces discomfort," "suppresses a decrease in motivation to be active," and "prevents muscle function decline." Energy production may refer to energy production in cells or mitochondria. In one aspect of the present invention, the composition of the present invention is preferably a food or beverage labeled with the above-mentioned label. The above-mentioned label may also be a label indicating that the composition is used to obtain the above-mentioned function. The above-mentioned label may be attached to the composition itself, or to the container or packaging of the composition.

[0046] The present invention also encompasses the use of a sesamin-class compound and an astaxanthin-class compound for producing a composition for improving energy production, suppressing a decrease in energy production, or maintaining energy production, in which the weight ratio of the sesamin-class compound (as converted into sesamin) to the astaxanthin-class compound (as converted into astaxanthin) is 0.05 to 15.

[0047] The present invention also encompasses the following methods: A method for suppressing, alleviating, or ameliorating fatigue, which comprises administering a composition containing the following components (A) and (B): (A) a sesamin-class compound and (B) an astaxanthin-class compound, wherein the weight ratio ((A) / (B)) of component (A) (converted to sesamin) to component (B) (converted to astaxanthin) is 0.05 to 15; and a method for improving, suppressing a decrease in, or maintaining energy production, which comprises administering the above composition.

[0048] The present invention also encompasses the following uses. Use of the following composition for improving, inhibiting a decline, or maintaining energy production; Use of the following composition for inhibiting, alleviating, or ameliorating fatigue or tiredness associated with aging: A composition containing the following components (A) and (B): (A) a sesamin-class compound and (B) an astaxanthin-class compound, wherein the weight ratio ((A) / (B)) of component (A) (converted to sesamin) to component (B) (converted to astaxanthin) is 0.05 to 15. The above method or use may be a therapeutic method or use or a non-therapeutic method or use. Administration of the above composition to a subject makes it possible to improve, inhibit a decline, or maintain mitochondrial function. Administration of the above composition to a subject provides the effects of improving, inhibiting a decline, or maintaining energy production, and inhibiting, alleviating, or ameliorating fatigue or tiredness associated with aging.

[0049] In the above uses and methods, the preferred aspects of the sesamin-class compound, the astaxanthin-class compound, and the ratio thereof are the same as those of the composition of the present invention described above. As the sesamin-class compound and the astaxanthin-class compound, one type or two or more types may be used. In the above uses, it is preferable to administer (ingest) the composition to a subject at least once a day, for example, once to several times a day (e.g., two to three times a day). In the above uses, it is preferable to administer (ingest) the composition orally. The above uses are preferably in humans or non-human mammals, more preferably in humans.

[0050] In the above-mentioned uses, one or more sesamin-class compounds and one or more astaxanthin-class compounds may be used in an amount sufficient to achieve the desired effect (which may also be referred to as an effective amount). The preferred dosages and administration targets of the sesamin-class compounds and astaxanthin-class compounds are the same as those for the composition of the present invention described above.

[0051] In this specification, a numerical range expressed by a lower limit and an upper limit, i.e., "lower limit to upper limit," includes both the lower limit and the upper limit. For example, a range expressed by "1 to 2" means 1 or more and 2 or less, including 1 and 2. In this specification, the upper and lower limits may be any combination of ranges. All academic literature and patent documents described in this specification are incorporated herein by reference.

[0052] The present invention will be described in more detail below with reference to examples, although the present invention is not limited to these examples.

[0053] <Evaluation test of energy production by sesamin metabolites and astaxanthin> The sesamin metabolite SC1 ((7α,7'α,8α,8'α)-3',4'-methylenedioxy-7,9':7',9-diepoxylignane-3,4-diol) was used as the sesamin-class compound. Astaxanthin derived from Blakeslea trispora (Sigma-Aldrich) was used. Unless otherwise specified, the medium used to culture TIG-3 cells (human fetal lung fibroblasts) was prepared by adding 10% Fetal Bovine Serum (SIGMA, 172012-500 mL) and 1% Antibiotic Antimycotic Mixed Stock Solution (Nacalai Tesque, 02892-54) to MEM high glucose (Nacalai Tesque, 08458-45).

[0054] Example 1 To investigate the effect on energy production, TIG-3 cells were seeded in a 6-well plate in a medium to which sesamin metabolite (hereinafter also referred to as SC1) and astaxanthin (hereinafter also referred to as Asta) had been added at 250 nM and 890 nM, respectively, and incubated at 37°C under CO ２ (5%) for 3 weeks. For subculture on the third day after the start of culture, 2.0 × 10 ５ In the case of subculture on the 4th day of culture, the cell density was 1.0 × 10 ５After 3 weeks, the cells were seeded onto a dedicated plate for the XF analyzer and incubated at 37°C in CO ２ The cells were cultured for 24 hours under conditions of 0.1% CO₂ (5%). The medium was then replaced with analytical medium, and the oxygen consumption rate (pmol / min) was analyzed using an analytical instrument (XF analyzer, Agilent Corporation). After the analysis was completed, the nuclei were stained with Hoechst He, and the cells were photographed using a fluorescence microscope BZ-x (Keyence Corporation), and the number of cells was counted using image analysis. By measuring the decrease in oxygen consumption of live cells using the XF analyzer, the amount of ATP production, which indicates mitochondrial function, can be evaluated. Specifically, after measuring the oxygen consumption rate of basal respiration of live cells in the wells, an ATP synthase inhibitor (oligomycin) was added to the wells, and the decrease in oxygen consumption rate (pmol / min / 10 ) due to the addition of oligomycin was calculated. ２ The basal respiration rate (basal respiration rate) was measured and used as the amount of ATP produced. Basal respiration indicates the cellular energy demand under baseline conditions, and a portion of the basal respiration is used for ATP production. The decrease in oxygen consumption rate due to the addition of oligomycin indicates the amount of ATP produced. The results are shown in Table 1. The weight ratio of SC1 to astaxanthin in terms of sesamin in the medium used in Example 1 (hereinafter also referred to as sesamin-equivalent SC1 / astaxanthin (weight ratio)) was 0.17.

[0055] Comparative Example 1 The amount of ATP produced was measured in the same manner as in Example 1, except that the medium used for culturing TIG-3 cells contained a sesamin metabolite (SC1) at a concentration of 250 nM and did not contain astaxanthin. The results are shown in Table 1.

[0056] Comparative Example 2 The amount of ATP produced was measured in the same manner as in Example 1, except that the medium used for culturing TIG-3 cells contained an astaxanthin concentration of 890 nM and did not contain sesamin metabolite (SC1). The results are shown in Table 1.

[0057] Example 2 The amount of ATP produced was measured in the same manner as in Example 1, except that the concentrations of sesamin metabolite (SC1) and astaxanthin in the medium for culturing TIG-3 cells were 1 μM and 350 nM, respectively. The results are shown in Table 2. The weight ratio of SC1 / astaxanthin, calculated as sesamin, in the medium used in Example 2 was 1.7.

[0058] Comparative Example 3 The amount of ATP produced was measured in the same manner as in Example 1, except that the medium used for culturing TIG-3 cells contained a sesamin metabolite (SC1) at a concentration of 1 μM and did not contain astaxanthin. The results are shown in Table 2.

[0059] Comparative Example 4 The amount of ATP produced was measured in the same manner as in Example 1, except that the medium used for culturing TIG-3 cells contained an astaxanthin concentration of 350 nM and did not contain sesamin metabolite (SC1). The results are shown in Table 2.

[0060] Example 3 ATP production was measured in the same manner as in Example 1, except that the concentrations of sesamin metabolite (SC1) and astaxanthin in the culture medium for culturing TIG-3 cells were 3 μM and 214 nM, respectively. The results are shown in Table 3. The sesamin-equivalent SC1 / astaxanthin (weight ratio) in the culture medium used in Example 3 was 8.3.

[0061] Comparative Example 5 The amount of ATP produced was measured in the same manner as in Example 1, except that the medium used for culturing TIG-3 cells contained a sesamin metabolite (SC1) at a concentration of 3 μM and did not contain astaxanthin. The results are shown in Table 3.

[0062] Comparative Example 6 The amount of ATP produced was measured in the same manner as in Example 1, except that the medium used for culturing TIG-3 cells contained an astaxanthin concentration of 214 nM and did not contain sesamin metabolite (SC1). The results are shown in Table 3.

[0063] Comparative Example 7 The amount of ATP produced was measured in the same manner as in Example 1, except that the medium used for culturing TIG-3 cells contained a sesamin metabolite (SC1) at a concentration of 3 μM and did not contain astaxanthin. The results are shown in Table 4.

[0064] Comparative Example 8 The amount of ATP produced was measured in the same manner as in Example 1, except that the medium used for culturing TIG-3 cells contained an astaxanthin concentration of 107 nM and did not contain sesamin metabolite (SC1). The results are shown in Table 4.

[0065] (Comparative Example 9) ATP production was measured in the same manner as in Example 1, except that the concentrations of sesamin metabolite (SC1) and astaxanthin in the medium were 3 μM and 107 nM, respectively. The results are shown in Table 4. The weight ratio of SC1 / astaxanthin, calculated as sesamin, in the medium used in Comparative Example 8 was 16.7.

[0066] Reference Example 1: Except for changing the medium for culturing TIG-3 cells to a medium that did not contain sesamin metabolite (SC1) or astaxanthin, the amount of ATP produced was measured in the same manner as in Example 1. This was used as a control (CTL) for Examples 1 and 3 and Comparative Examples 1, 2, and 5 to 9, and the results are shown in Tables 1, 3, and 4.

[0067] (Reference Example 2) The amount of ATP produced was measured in the same manner as in Example 1, except that the medium for culturing TIG-3 cells was changed to a medium that did not contain sesamin metabolite (SC1) or astaxanthin. This was used as a control (CTL) for Example 2 and Comparative Examples 3 and 4, and the results are shown in Table 2.

[0068]

[0069]

[0070]

[0071]

[0072] In Tables 1 to 4, "measured value" (pmol / min / 10 ２ The ATP production amount (amount of decrease in oxygen consumption rate due to ATP synthase inhibition) calculated above is shown in the table (n=3). The improvement rates shown in Tables 1 to 4 are values ​​obtained by subtracting 100 (%) from the "relative value (%)" of the ATP production amount in Examples 1 to 3 and Comparative Examples 1 to 9, when the average ATP production amount in the control (CTL) is set to 100 (%). The Dunnett's test was performed on the obtained results, and the p-values ​​are shown in Tables 1 to 4.

[0073] As shown in Tables 1 to 4, in Comparative Examples 2 to 8, treatment with SC1 or Asta alone also increased ATP production compared to the control group (Reference Example 1), confirming the effects of improving energy production and inhibiting or maintaining its decline. As shown in Table 1, the improvement rate in Example 1, in which SC1 (equivalent to sesamin) and Asta were combined at a weight ratio of 1:6, was greater than the sum of the improvement rates in Comparative Examples 1 and 2, in which SC1 and Asta were treated alone at the same ratios as in Example 1. Similarly, as shown in Table 2, the improvement rate in Example 2, in which SC1 (equivalent to sesamin) and Asta were combined at a weight ratio of 10:6, was also greater than the sum of the improvement rates in Comparative Examples 3 and 4. Similarly, as shown in Table 3, the improvement rate in Example 3, in which SC1 (equivalent to sesamin) and Asta were combined at a weight ratio of 50:6, was also greater than the sum of the improvement rates in Comparative Examples 5 and 6. On the other hand, as shown in Table 4, when SC1 (as sesamin) and Asta were combined at a weight ratio of 100:6 (Comparative Example 9), ATP production was reduced compared to the control group (Reference Example 1), and no effect was obtained from the combination of SC1 and Asta. These results confirmed that in Examples 1 to 3, ATP production did not simply increase additively with the treatment with SC1 and Asta, but rather that the combination of SC1 and Asta at a specified ratio resulted in a synergistic increase in ATP production. In other words, it was confirmed that a composition containing SC1 and Asta at a specified ratio exhibited a synergistic effect of increasing, inhibiting a decrease in, or maintaining ATP production due to the inclusion of both compounds, and that this effect was exerted even at low doses.

[0074] From the above, it has become clear that combining sesamin-class compounds and astaxanthin-class compounds in a specified ratio exhibits a synergistic effect of increasing ATP production and suppressing or maintaining its decline. This confirms that a composition containing sesamin-class compounds and astaxanthin-class compounds in a specified ratio can effectively improve, suppress or maintain mitochondrial function. Furthermore, using a combination of sesamin-class compounds and astaxanthin-class compounds in a specified ratio can effectively improve, suppress or maintain energy production. This, in turn, can suppress, alleviate or improve, for example, fatigue or tiredness associated with aging.

[0075] Example 4 Evaluation of Energy Production in Humans (Evaluation Sample) Test foods (soft capsules) containing 10 mg (as sesamin equivalent) of sesamin-family compounds and 6 mg (astaxanthin equivalent) of astaxanthin-family compounds per three capsules were prepared. The weight ratio of astaxanthin-family compounds (astaxanthin equivalent) to sesamin-family compounds (as sesamin equivalent) in the test foods was 1.7. The sesamin-family compounds used were a mixture of sesamin and episesamin in a sesamin:episesamin weight ratio of approximately 1:1, and the astaxanthin-family compounds were derived from Haematococcus algae extract. A control food was prepared using the same ingredients as the test foods except that no sesamin-family compounds or astaxanthin-family compounds were used. The test foods and control foods had similar amounts of calories, protein, lipids, and carbohydrates per three capsules, and the two foods were indistinguishable from each other based on appearance, etc. (Evaluation Method) Before and 6 weeks after ingestion of the test food or control food, oxygen consumption metabolism was measured using a near-infrared spectroscopy device to evaluate energy production and metabolism. The test was conducted according to the method described in Dynamic Medicine 2004, 3:2. The specific test method is as follows: (1) Subjects: 77 healthy adult males (37 in the test food group and 35 in the control food group) were analyzed. (2) Intake Method of Test Food or Control Food: Subjects in the test food group were instructed to take the test food (3 tablets per day). Subjects in the control food group were instructed to take the control food (3 tablets per day). The test food and control food were orally taken once daily for 6 weeks. (3) Evaluation of energy production Before and after 6 weeks of intake, the rate of decrease in muscle tissue oxygen concentration during blood flow occlusion on the non-dominant arm immediately after exercise was measured using a near-infrared spectroscopy device. The rate of decrease in muscle tissue oxygen concentration during occlusion was defined as muscle oxygen consumption, and the change in muscle oxygen consumption obtained over 6 minutes was fitted to a first-order exponential function to determine the recovery rate (recovery time constant). The change between before and 6 weeks of intake is shown in Table 5.

[0076]

[0077] As shown in Table 5, subjects who ingested the test food had a significantly faster recovery rate of muscle oxygen consumption than subjects who ingested the control food. This effect is thought to be due to the improved energy production effect of the food, which contains a specified weight ratio of sesamin-class compounds and astaxanthin-class compounds.

[0078] (Example 5) <Evaluation of Anti-Fatigue Effects in Humans> (Evaluation Method) Men and women aged 40 to 65 years (136 in the test food group and 136 in the control food group) who tend to feel fatigue with age and in daily life were administered the test food (3 tablets per day) or the control food (3 tablets per day) for 8 weeks. Test days were set before the start of intake, at week 4, and at week 8 of intake. On the test days, fatigue was measured after waking up. A visual analogue scale (VAS) was used to evaluate fatigue. Specifically, the subjects were asked to mark their level of fatigue on a 10 mm line, with the left end (0 mm) representing "the best feeling of not feeling tired at all" and the right end (100 mm) representing "the worst feeling of being so exhausted that they could do nothing." The distance (mm) from the left end of the 10 mm line to the mark position was measured and used as a measurement value of fatigue. The changes in fatigue sensation at 4 weeks and 8 weeks after intake were calculated using the following formulas (i) to (ii): Change in fatigue sensation = (fatigue sensation at 4 weeks after intake) - (fatigue sensation at 0 weeks) Formula (i) Change in fatigue sensation = (fatigue sensation at 8 weeks after intake) - (fatigue sensation at 0 weeks) Formula (ii)

[0079] (Analysis 1: Analysis of efficacy analysis subjects) The results of the analysis of changes in fatigue sensation after excluding subjects who discontinued, withdrew, or violated the management guidelines, and subjects who met the exclusion criteria (25 subjects in the test food group, 22 subjects in the control food group), are shown in Table 6. Significance tests for differences between groups were performed using unpaired t-tests (difference between groups (relative to fatigue sensation in the control food group) *: p<0.05, #: p<0.10).

[0080]

[0081] (Analysis 2: Subgroup analysis) The VAS scores at the screening test were divided into two strata: those less than the overall median (60 mm) and those equal to or greater than the median. The results (change in fatigue) analyzed using formulas (i) and (ii) are shown in Table 7. The significance test was performed using an unpaired t-test (difference between groups (relative to fatigue in the control food group): p<0.10).

[0082]

[0083] Compared to the group with small VAS scores and low fatigue during the screening test, the group with large VAS scores and high fatigue during the screening test tended to show lower values ​​after both week 4 and week 8 of intake due to test food intake. This suggests that sesamin-related compounds and astaxanthin-related compounds are expected to be particularly effective in people who experience high levels of fatigue in their daily lives.

[0084] (Analysis 3: Subgroup analysis) The frequency of exercise at the time of the cleaning test was divided into two strata: "hardly ever to several times a month" and "more than once a week to every day." The results of the analysis using formulas (i) and (ii) (change in fatigue sensation) are shown in Table 8. The significance test was performed using an unpaired t-test (difference between groups (relative to fatigue sensation in the control food group) *: p<0.05).

[0085]

[0086] In the group with a high exercise frequency (once a week or more / daily), the values ​​were significantly lower after four weeks of intake. This suggests that combining moderate exercise may enhance the fatigue-reducing effects of sesamin-related compounds and astaxanthin-related compounds.

Claims

1. A composition for improving energy production and suppressing its decline or maintaining it, comprising the following components (A) and (B) as active ingredients: (A) a sesamin-based compound and (B) an astaxanthin-based compound, wherein the weight ratio ((A) / (B)) of component (A) (converted to sesamin) to component (B) (converted to astaxanthin) is 0.05 to 15.

2. The composition according to claim 1, which is used to inhibit, reduce or improve fatigue or tiredness associated with aging.

3. The composition according to claim 1 or 2, wherein the improvement, suppression of decline, or maintenance of energy production is mediated by the improvement, suppression of decline, or maintenance of mitochondrial function.

4. The composition according to claim 1 or 2, wherein the sesamin-class compound is at least one compound selected from the group consisting of sesamin, episesamin and metabolites thereof.

5. The composition according to claim 1 or 2, wherein the astaxanthin-class compound is at least one compound selected from the group consisting of astaxanthin and its derivatives.

6. The composition according to claim 1 or 2, wherein the astaxanthin-class compound is derived from an extract of Haematococcus algae.

7. The composition according to claim 1 or 2, which is an oral composition.

8. The composition according to claim 1 or 2, which is a food or drink.

9. The composition according to claim 1 or 2, which is used for people who experience strong fatigue in their daily lives.

10. The composition according to claim 1 or 2, used in combination with exercise.

11. The composition according to claim 1 or 2, which is labeled with one or more of the following: "aids energy production or metabolism," "aids cellular energy production or metabolism," "aids energy production or metabolism in intracellular mitochondria," "maintains and improves vitality and energy," "reduces fatigue associated with aging," "reduces fatigue associated with aging," "for those who become more susceptible to fatigue with age," "reduces fatigue that has become more noticeable with age," "reduces fatigue experienced in daily life," "reduces fatigue in daily life," "reduces general malaise," "reduces lethargy," "reduces feelings of weakness," "reduces discomfort," "suppresses loss of motivation to be active," and "prevents muscle function decline." 12. A method for improving, suppressing a decrease in, or maintaining energy production, comprising administering a composition containing the following components (A) and (B): (A) a sesamin-based compound and (B) an astaxanthin-based compound, wherein the weight ratio ((A) / (B)) of component (A) (converted to sesamin) to component (B) (converted to astaxanthin) is 0.05 to 15.

13. Use of a composition containing the following components (A) and (B): (A) a sesamin-based compound and (B) an astaxanthin-based compound, in which the weight ratio ((A) / (B)) of component (A) (converted to sesamin) to component (B) (converted to astaxanthin) is 0.05 to 15, for improving, inhibiting a decrease in, or maintaining energy production.